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1 2011 GREETINGS On behalf of the Planning, Organizing and Scientific Committees of the International Congress of Pharmacology Mexico 2011, we welcome all attendees. The joint meeting of the XXXIV Congreso Anual de la Asociación Mexicana de Farmacología A. C. (AMEFAR), the 54th Annual Meeting of the Western Pharmacology Society (WPS), and the 2nd Latin American Meeting of the International Society of Pharmacoepidemiology (ISPE), is the sixth occasion since 1966, that Mexican and Northamerican Pharmacologists gather together to continue efforts for spreading and updating knowledge for continuous development of Pharmacology, as a basic science fundamental for therapeutic advances. The transition towards a more preventive Medicine in a scenario of complex diseases demands a personalized diagnostic and treatment approaches, particularly those related to the use of medicaments. The contribution of outstanding Clinical and Basic Pharmacology and Therapeutics Researchers in the academic program of the International Congress of Pharmacology Mexico 2011 highlights the key essence of 21st Century Pharmacology as an integrated and integrative science. Sustainable development of Pharmacology and Therapeutics is a complex task that requires the cooperation of all parties involved. Hereby we acknowledge the enthusiastic participation of higher education institutions, health care institutions, academic associations, government regulatory agencies, editorial and pharmaceutical companies whose cooperation made this meeting possible. Special mention deserves the generosity of the Faculty of Medicine of the Universidad Nacional Autónoma de México (UNAM) by hosting the International Congress of Pharmacology Mexico 2011 in the splendid Palace of the School of Medicine in Mexico City. Our recognition to Dr. Enrique Graue Wiechers, Dean of the Faculty of Medicine, UNAM, and Honorary President of this Congress. María Dolores Ramírez-González, Ph.D. President of the Planning and Organizing Committees International Congress of Pharmacology Mexico 2011 May 16th to the 20th, 2011 Mexico City 2 3 INTERNATIONAL CONGRESS OF PHARMACOLOGY MEXICO 2011 PLANNING COMMITTEE María Dolores Ramírez-González, Ph.D. AMEFAR President Laurence Brunton, Ph.D. WPS President Maribel Salas, Ph.D. ISPE Latin America Delegate ORGANIZING COMMITTEE María Dolores Ramírez-González, Ph.D. AMEFAR President Laurence Brunton, Ph.D. WPS President Claudia Gómez Acevedo, AMEFAR General Secretary Rosa Ventura Martínez, AMEFAR Treasurer Maribel Salas, Latin America Delegate of ISPE SCIENTIFIC COMMITTEE Enrique Hong Chong, AMEFAR Executive Secretary Marco Martínez Ríos María Elena Medina-Mora José Luis Reyes Angélica Ocampo Marcela López Cabrera Egbert Sánchez Van der Kast Agustín Rogelio Mosqueda Guadalupe Baños Marhaber Bertha Prieto Gómez Jesús Adolfo García Sáinz Aurora de la Peña Díaz Eduardo Anglés-Cano Gilberto Vargas-Alarcón 4 Germán Chamorro Cevallos María Teresa Espinosa Meléndez Oscar Presbítero Arriaga Jesús Antonio González Hermosillo Carlos M. Villalón Herrera Antonio Caso Marasco Elia Brosla Naranjo Rodríguez J. Moisés Álvarez Rueda Abraham Hartzema Stan Edlavitch Chirs Delaney Iain L. Buxton Augusto Bondani Guasti Alejandra Rosete Reyes Bruno Escalante Elena Guadalupe Ramírez López Andrés E. Castell Rodríguez Eduardo Calixto González Carlos Viesca Treviño Patricia Yahuaca Mendoza Susana Tera Ponce Georgina Araceli Torres Vargas Isabel Saad Villegas 5 INTERNATIONAL CONGRESS OF PHARMACOLOGY MEXICO 2011 JOINT MEETING OF: XXXIV CONGRESO ANUAL DE LA ASOCIACIÓN MEXICANA DE FARMACOLOGÍA 54th ANNUAL MEETING OF THE WESTERN PHARMACOLOGY SOCIETY 2nd LATIN AMERICAN MEETING OF THE INTERNATIONAL SOCIETY OF PHARMACOEPIDEMIOLOGY May 16th to the 20th , 2011 MONDAY MAY THE 16th, 2011 07:00 - 08:00 h Registration 08:00 - 08:20 h Opening Ceremony MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Presidium: Dr. Enrique Graue Wiechers. Honorary President of the Meeting. Dean of the Faculty of Medicine, Universidad Nacional Autónoma de México. Dra. María Dolores Ramírez González, President of the Asociación Mexicana de Farmacología A. C. and President of the Organizing Committee Dr. Laurence Brunton, President of the Western Pharmacology Society. VicePresident of the Organizing Committee Guests of Honor: Dra. María Elena Medina Mora. General Director of the Instituto Nacional de Psiquiatría ―Dr. Ramón de la Fuente‖ Dr. Marco A. Martínez Ríos. General Director of the Instituto Nacional de Cardiología ―Dr. Ignacio Chávez‖ (TO BE CONFIRMED) Dra. Marcela López Cabrera, General Director of the Instituto para la Atención y Prevención de las Adicciones de la Ciudad de México Rosa Amalia Bobadilla MD., PhD. Directora de la Escuela Superior de Medicina del Instituto Politecnico Nacional, Mexico (TO BE CONFIRMED) Dr. George Kunos, Scientific Director of NIAA, NIH Dr. Eduardo Anglés-Cano. Directeur de Recherche 1. Institut National de la Santé et de la Recherche Médicale (INSERM) 6 Dr. Enrique Hong Chong. Executive Secretary of the Asociación Mexicana de Farmacología A. C. and President of the Scientific Committee Dr. Augusto Bondani Guasti. Incoming President of the Asociación Mexicana de Farmacología A. C. Dra. Carolina Escobar. President of the Sociedad Mexicana de Ciencias Fisiológicas A.C. (TO BE CONFIRMED) Dra. Alejandra Rosete. Professor of Pharmacovigilance (UNAM, ULSA), President of Mexico Chapter International Society of Pharmacovigilance, member of ACSoMPWHO Dr. Xavier Lozoya Legorreta, Vice-President of the Asociación Mexicana de Fitoterapia A.C. Dr. Antonio Caso Marasco, President of the Colegio Mexicano de Farmacoeconomía and of the Mexican Chapter of the International Society of Pharmacoeconomics Dr. Jorge González Antequera, Presidente de la Asociación Mexicana de Farmacovigilancia A.C. Dra. Patricia Yahuaca Mendoza, Regional Delegate of AMEFAR Dra. María Teresa Espinosa y Dr. Oscar Presbítero Arriaga. Founding Members of the Odontologists’ Chapter of AMEFAR Esp Adic. Lic. Angélica Ocampo, Head of the Clínica Contra el Tabaquismo. Hospital General de México, SS. Ing. Hugo Setzer Letsche, General Director of Editorial El Manual Moderno S.A. de C. V., Industrial Associate of the Asociación Mexicana de Farmacología A. C. Special Guests: Former AMEFAR Presidents: Dr. Andrés Navarrete Castro, Dr. Carlos Castilo Henkel, Dr. Gilberto Castañeda Hernández, Dr. J. Moisés Álvarez Rueda, Dr. Luis Antonio Barragán Díaz Infante, Dr. Horacio Vidrio López, Dr. José Antonio Rojas Ramírez, Dr. Miguel Cervantes, Dr. Rodolfo Rodríguez Carranza Former WPS President: Dr. Carlos M. Villalón Herrera ISPE Delegates: Abraham Hartzema, Stan Edlavitch, Chris Delaney Distinguished Members of the Scientific Committee: Symposia Organizers and Lecturers AMEFAR and WPS Associates 08:20 - 08:30 h Coffee break 7 MONDAY MAY THE 16th, 2011 08:30 – 10:30 h Symposium 1: Addictions MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) 08:30 – 08:50 h Epidemiological overview of addictions. Dra. María Elena Medina-Mora. General Director of the Instituto Nacional de Psiquiatría ―Dr. Ramón de la Fuente‖ 08:50 – 09:10 ¿How to understand addictions? Esp Adic. Lic. Angélica Ocampo, Head of the Clínica Contra el Tabaquismo. Hospital General de México, SS. 09:10 – 09:30 h From neurobiology to prevention of addictions. Dr. Luis Solis Rojas. Instituto para la Atención y Prevención de las Adicciones de la Ciudad de México. 09:30 – 09:40 h Questions and comments 09:40 – 10:20 h PLENARY LECTURE: From addictions to cardiovascular and metabolic diseases. MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Dr. George Kunos. Scientific Director NIAAA, National Institute of Health U.S. 10:20 – 10:30 h Questions and comments 10:30 - 10:40 h Coffee break 10:40 - 11:30 h PLENARY LECTURE: From neurobiology to policies for attention and prevention of addictions public MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Dra. Marcela López Cabrera. General Director of the Instituto para la Atención y Prevención de las Adicciones de la Ciudad de México. 11:30 – 11:40 h Questions and comments 11:40 - 12:50 h Lunch break 12:50 - 13:10 h ―PATIO DE PIEDRA‖ Opening of the "Pavillion of the Pharmacology Book" Chairman: Ing. Hugo Setzer Letsche, General Director of Editorial El Manual Moderno S.A. de C. V., Industrial Associate of the Asociación Mexicana de Farmacología A. C. 13:10 – 13:20 h Coffee break 8 13:20 - 14:40 h Symposium 2: Current Trends information on Pharmacology in the retrieval of MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Egbert Sánchez Vanderkast 13:20 – 13:35 h Licensing models for information retrieval and access to institutional repositories. Dr. Jesús Francisco García Pérez. Coordinador de la Biblioteca del Instituto de Investigaciones Sociales, Universidad Nacional Autónoma de México 13:35 – 14:00 h Specialized databases in Pharmacology. An approach to the current situation. Mtra. Isabel Margarita Lugo Hubp. Sub directora de Servicios de Información Especializada de la Dirección General de Bibliotecas, Universidad Nacional Autónoma de México 14:00 - 14:15 h Access to medical information in a digital world: challenges for the librarian. Mtra. Alejandra Martínez del Prado. Biblioteca de la Facultad de Medicina, Universidad Nacional Autónoma de México y Coordinadora de la Sección de Bibliotecas en Ciencias de la Salud de la AMBAC 14:15 – 14:30 h The electronic book in the university environment. Mtro. Miguel Gama Ramírez. Coordinador de la Biblioteca ―Eduardo García Máynez‖ of the Instituto de Investigaciones Filosóficas, Universidad Nacional Autónoma de México 14:30 – 14:40 h Questions and comments 14:40 - 14:50 h Coffee break 14:50 - 16:30 h Symposium 3: Obesity and diabetes MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Agustín Rogelio Mosqueda-García Honorary Chairman: Dr. Carlos Posadas Romero. Head of the Departmento de Endocrinología, Instituto Nacional de Cardiología ―Dr. Ignacio Chávez‖ 14:50 – 15:35 h Dr. Agustín Rogelio Mosqueda-García. New Pharmacological Approaches for Treating Type-2 Diabetes. Executive Director Clinical Pharmacology. Deputy HELC Chair & MSAG Lead. AstraZeneca LP 15:35 – 16:20 h Dr. Enrique Mendoza Pérez. Body fat disposition and cardiovascular risk. Departamento de Endocrinología. Instituto Nacional de Cardiología ―Dr. Ignacio Chávez‖ 16:20 – 16:30 h Questions and comments 16:30 - 16:40 h Coffee break 9 16:40 - 18:00 h Symposium 4: Metabolic syndrome MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairwomen: Dra. Guadalupe Baños-Marhaber y Dra. Bertha Prieto Gómez 16:40 – 16:55 h Mechanisms of hyperinsulinemia in metabolic syndrome. Dra. Marcia Hiriart Urdanivia. Director of the Instituto de Fisiología Celular, Universidad Nacional Autónoma de México 16:55 – 17:25 h Metabolic syndrome in children. Dra. Yadira Eugenia Pastrana Fernández. Endocrinología Pediátrica, Hospital Ángeles Metropolitano 17:25 – 17:50 h Some characteristics of a model of metabolic syndrome. Dra. Guadalupe Baños Marhaber. Jefa de la Unidad de Biomedicina, Instituto Nacional de Cardiología ―Dr. Ignacio Chávez‖ 17:50 – 18:00 h Questions and comments 18:00 - 18:50 h PLENARY LECTURE: From Himsworth to Syndrome X to the Metabolic Syndrome MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairwoman: Dra. Guadalupe Baños Marhaber Dr. Gerald Reaven. Division of Cardiovascular Medicine, Falk CVRC, Stanford Medical Center 18:50 - 19:00 h Coffee break 19:00 - 20:00 h Students’ gathering with Experts and Authors of Pharmacology Books 20:00 - 21:00 h Welcome reception 10 TUESDAY MAY THE 17th, 2011 07:00 - 08:00 h Registration 08:00 - 10:00 h Symposium 5: G protein coupled receptors IN HONOR OF DR. HORACIO VIDRIO LÓPEZ MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. J. Adolfo García Sáinz. Profesor Investigador del Instituto de Fisiología Celular, Universidad Nacional Autónoma de México 08:00 – 08:10 h Introduction. J. Adolfo García-Sáinz. 08:10 – 08:30 h Continuous Angiotensin II evokes cardiovascular effects inversely associated to alpha-1D-adrenoceptors expression in aorta of Wistar rats. Rafael Villalobos-Molina. Jefe de la Division de Investigacion y Posgrado. Unidad de Investigacion en Biomedicina. Facultad de Estudios Superiores Iztacala, UNAM 08:30 – 08:50 h Interactions of adrenergic receptors and the renin-angiotensin system during pregnancy and preclampsia. Pedro LópezSánchez. Jefe del Laboratorio de Farmacología Molecular.Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional 08:50 – 09:30 h Signaling by G-protein-coupled receptors: New results challenge old ideas. **Paul Insel. Professor, Pharmacology / Medicine Hematologic Malignancies Program. UC San Diego Moores Cancer Center 09:30 – 09:50 h Roles of paracrine/ autocrine communication in alpha-1adrenoceptor phosphorylation/ desensitization. J. Adolfo García-Sáinz. . Profesor Investigador del Instituto de Fisiología Celular, Universidad Nacional Autónoma de México 09:50 – 10:00 h Questions and comments **SPONSORED BY INSTITUTO DE FISIOLOGÍA CELULAR, UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO 10:00 – 10:10 h Coffee break 11 10:10 A 12:10 h Symposium 6: Thrombosis MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairmen: Dr. Eduardo Anglés-Cano and Dra. Aurora de la Peña Díaz 10:10 – 10:35 h Physiopathology of thrombosis: procoagulant microparticles.Dra. Aurora de la Peña Díaz. Profesor Titular ―A‖. Facultad de Medicina, Universidad Nacional Autónoma de México. Laboratorio de Trombosis y Fibrinólisis, Departamento de Biología Molecular. Instituto Nacional de Cardiología ―Dr. Ignacio Chávez‖. S.N.I. 10:35 – 11:00 h Thrombosis-novel drug targets: platelets. Dr. Abraham MajlufCruz. Jefe de la Clínica de Hemostasia y Trombosis del Hospital Mc Gregor del Instituto Mexicano del Seguro Social. S.N.I. 11:00 – 11:25 h Thrombosis: advances in new anticoagulant therapy. Dr. Carlos Martínez Murillo. Jefe de la Clínica de Hemostasia y Trombosis del Hospital General de México, Secretaría de Salud. Investigador en Ciencias Médicas de la Secretaría de Salud. Jefe de Programas Médicos. División de Excelencia Clínica. Dirección de Prestaciones Médicas, Jefe de UMAE. IMSS. S.N.I. Presidente de la Agrupación Mexicana para el Estudio de la Hematología, A.C. 11:25 – 11:50 h Fibrinolytic cross-talk: antithrombotic microparticles. Dr. Eduardo Anglés-Cano. Directeur de Recherche 1. Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 919. Serine Proteases et Pathologie Nerovasculaire. Cyceron, Caen, France. 11:50 – 12:10 h Questions and comments 10:10-12:10 h Symposium 7: Dental Pain GRAND HALL (PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA) Chairmen: Dra. María Teresa Espinosa Meléndez and Dr. Oscar Presbítero Arriaga 10:10 – 10:25 h History of dental analgesia and anaesthesia. Dr. José Sanfilippo y Borras. Coordinador de Enseñanza del Departamento de Historia y Filosofía de la Medicina, Facultad de Medicina, Universidad Nacional Autónoma de México 10:25 – 11:05 h Physiopathology of dental pain. Dra. María Teresa Espinosa Meléndez. Profesora de la Facultad de Odontología, Universidad Nacional Autónoma de México 11:05 - 11:35 h Pain ATM: etiology, diagnosis and treatment. Dr. Adolfo Pérez Brignani. Benemérita Universidad Autónoma de Puebla 12 11:35 - 12:00 h Dental emergencies’ management. Dr. Óscar Presbítero Arriaga. Professor of Pharmacology, Westhill University Mexico 12:00 – 12:10 h Questions and comments 12:10 – 12:20 h Coffee break 12:20 - 14:20 h Symposium Diseases 8: Pharmacogenetics of Cardiovascular MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Gilberto Vargas Alarcón 12:20 – 12:45 h Pharmacogenetics: ¿Why should it be studied in Mexico? Dr. Gilberto Vargas Alarcón 12:45 – 13:10 h Coronary intervencionism with Stents: restenosis angiographic patterns. Dr. Marco Antonio Peña Duque 13:10 – 13:35 h Polymorphisms associated to restenosis deveopment. and Dr. José Manuel Fragoso Lona 13:35 – 14:00 h Role of genetics in Clopidogrel response. Dra. Aurora de la Peña. 14:00 – 14:20 h Questions and comments 12:20 – 13:20 h Early presentation Terapéutica para Panamericana of the book Odontólogos¨ ¨Farmacología y Editorial Médica GRAND HALL (PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA) Dra. María Teresa Espinosa Meléndez, Editora Compiladora de la obra. 13:20 – 14:20 h Many Changes: Goodman Education in the U.S. & Gilman and Medical GRAND HALL (PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA) Dr. Laurence Brunton. Editor of the book 14:20 – 16:20 h CONGRESS COURSES 13 16:20 - 17:20 h PLENARY LECTURE : Hypertension MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Enrique Hong Chong Dr. Gerardo Gamba- Ayala Premio Nacional de Ciencias 2010 Head of the Departamento de Nefrología del Instituto Nacional de Cardiología ―Dr. Ignacio Chávez‖ 17:20 – 17:30 h Coffee break 17:30 - 18:30 h PANEL OF EXPERTS "Cardiovascular risk and metabolic syndrome" MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Jesús A. González Hermosillo Honorary Chairman: Dr. Enrique Hong Chong Panelists: Dr. Gerald Reaven Dr. George Kunos Dr. Eduardo Anglés-Cano 16:20 – 18:20 h Symposium 9: Spirulina GRAND HALL (PARANINFO DE LA ESCUELA DE MEDICINA) Chairman Dr. Germán Chamorro Cevallos Honorary Chairman: Dr. Laurence Brunton 16:20 – 16:25 h Introducción: Dr. Germán Chamorro Cevallos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. 16:25 – 16:45 h Propiedades farmacológicas de la Spirulina: Dr. Marco Antonio Juárez Oropeza, Facultad de Medicina, Universidad Nacional Autónoma de México 16:45 – 17:05 h Actividad anti-hígado graso de Spirulina: Dra. Patricia Victoria Torres Durán, Facultad de Medicina, Universidad Nacional Autónoma de México 17:05 – 17:25 h Spirulina como un agente antiviral. Dra. Blanca Lilia Barrón. Departamento de Microbiología. Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional 14 17:25 – 17:45 h Capacidad antioxidante de Spirulina: Dr. Jorge Vázquez Sánchez, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. 17:45 – 18:05 h Toxicología de la Spirulina. Dr. Germán Chamorro Cevallos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. 18:05 – 18:20 h Preguntas y comentarios 18:30 - 20:00 h POSTER SESSION MAIN SQUARE OF THE PALACE OF THE SCHOOL OF MEDICINE 19:30 - 20:00 h Business meeting of WPS ―AULA MAGNA‖ OF THE PALACE OF THE SCHOOL OF MEDICINE 20:00 – 21:00 h Guided nocturnal visit to the Palace of Medicine 15 WEDNESDAY MAY THE 18th, 2011 07:00 - 08:00 h Registration 8:00 – 10:00 h Symposium 10: Migraine MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Carlos M. Villalón Herrera 08:00 – 08:40 h Migraine: from skull trepanation in the Neolithic period to the development of modern in vivo animal models for the development of antimigraine drugs. Dr. Carlos M. Villalón Herrera Departamento de Farmacobiología. CINVESTAVCoapa 08:40 – 09:20 h The role of human in vitro and in situ models of migraine in the development of antimigraine drugs: building the bridge between animal experiments and patients. Dr. Antoinette Maassen van den Brink. Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands. 09:20 – 09:30 h Questions and comments 08:00 – 10:00 h Symposium 11: Pharmacoeconomy GRAND HALL (PARANINFO DE LA ESCUELA DE MEDICINA) Chairman: Dr. Antonio Caso Marasco. President of the Colegio Mexicano de Farmacoeconomía and President of the Mexican Chapter of the International Society of Pharmacoeconomy Honorary Chariman: 08:00 – 08:30 h Pharmacoeconomy in the globalized world. Dr. Antonio Caso Marasco. President of the Colegio Mexicano de Farmacoeconomía A.C. 08:30 – 09:15 h Models of pharmacoeconomy analysis and certainty of data. M. en C. Armando Nevarez Sida. Unidad de Economía de la Salud, IMSS 09:15 – 09:45 h Application of pharmacoeconomy criteria for constructing Formularies. Dr. Fernando García Contreras. Unidad de Economía de la Salud, IMSS 09:45 – 10:00 h Questions and comments 10:00 - 10:10 h Coffee break 16 10:10-12:10 h Plenary Lecture and Symposium 12: Advances in the Study of Melatonin: the 21st century MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairwoman: Dra. Elia Brosla Naranjo Rodríguez, Profesora Investigadora de la Facultad de Química, Universidad Nacional Autónoma de México Honorary Chairman: Dr. J. Moisés Álvarez Rueda, Former President of AMEFAR 10:10 – 10:40 h PLENARY LECTURE: Actions of melatonin as an antioxidant and as a cytoskeletal modulator: Implications in therapeutics Dra. Gloria Benítez King. Instituto Nacional de Psiquiatría ―Ramón de la Fuente Muñiz‖ 10:40 – 12:10 h Symposium 10:40 a 11:05 h Melatonin and its physiologic role in mmunomodulation. M. en C. Marcela Valdés Tovar. . Instituto Nacional de Psiquiatría ―Ramón de la Fuente Muñiz 11:05 – 11:30 h Design, synthesis and affinity binding of melatonin analogs. Dr. Alfonso Sebastián Lira Rocha, Facultad de Química, Universidad Nacional Autónoma de México 11:30 – 11:55 h Melatonin and analogues’ role in anxiety disorder. Dr. Elia Brosla Naranjo Rodríguez. Facultad de Química, Universidad Nacional Autónoma de México 11:55 – 12:10 h Questions and comments 12:10 - 12:20 h Coffee break 12:20 - 14:20 h Symposium 13: Pharmacoepidemiology MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairwoman: **Dra. Maribel Salas Ramírez 12:20 – 12:40 h Overview of Pharmacoepidemiology. **Dra. Maribel Salas. Latin America ISPE Delegate. Maribel Salas MD, DSc, MSc, FACP. Medical Director. CV Therapeutic Area. Safety Surveillance. US Patient Safety 12:40 – 13:10 h Importance of the pharmacoepidemiological study design. ** Stanley A. Edlavitch, PhD, MA, FACE. Professor of Epidemiology. Department of Psychiatry UMKC School of Medicine 13:10 – 13:35 h Data Sources in Pharmacoepidemiology for exposure, endpoints and covariates. **Dr. Abraham Hartzema, the Perry A. Foote Eminent Scholar. University of Florida College of Pharmacy 17 13:35 – 14:00 h Confounding and Biases in Pharmacoepidemiology. **Dr. Chris Delaney. University of Florida 14:00 – 14:20 h Questions and comments **SPONSORED BY THE PHARMACOEPIDEMIOLOGY 12:20 – 14:20 h INTERNATIONAL SOCIETY OF Symposium 14: Breast Cancer GRAND HALL (PARANINFO DE LA ESCUELA DE MEDICINA) Chairman: Dr. Sanford H. Barsky Honorary Chairman: Dr. Iain L. Buxton 12:20 – 12:55 h Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum. Iain L. O. Buxton, Professor of Pharmacology, University of Nevada School of Medicine, Reno, NV 12:55 – 13:00 h Questions and comments 13:00 – 13:35 h Semaphorin 3A potentiates metastatic disease by disrupting vascular barrier function. Lisette M. Acevedo, Project Scientist, Cheresh Laboratory, UCSD Moores Cancer Center, La Jolla, CA 13:35 – 13:40 h Questions and comments 13:40 – 14:15 h E-Cadherin and Its Dominant Oncogenes the Lymphovascular Sanford H. Barsky, Pathology, University USA 14:15 – 14:20 h Questions and comments Proteolytic Fragments Function as and Provide a Therapeutic Target within Embolus of Human Breast Cancer. Professor and Chair, Department of of Nevada School of Medicine, Reno, WESTERN PHARMACOLOGY SOCIETY SPONSORED SYMPOSIUM 14:20 – 16:20 h CONGRESS COURSES 16:20 - 18:20 h Symposium 15: Food Supplements MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Augusto Bondani Guasti Honorary Chairman: Dr. Laurence Brunton 16:20 – 16:55 h Food Supplements or fraud supplements? Dr. Augusto Bondani Guasti. Incoming President of AMEFAR and Advisor of the Comisión Federal para la Protección de Riesgo Sanitario (COFEPRIS), Mexico 18 16:55 – 17:30 h The charm of ‖pseudoscience‖ Ing.Mario Mendez Acosta. President of the Sociedad Mexicana para la Investigación Escéptica 17:30 – 18:05 h Miraculous medicaments CONFIRMED 18:05 – 18:20 h Questions and comments 16:20 – 18:20 h Symposium 16: Developing Passive Pharmacovigilance and COFEPRIS. TO BE GRAND HALL (PARANINFO DE LA ESCUELA DE MEDICINA) Chairwoman: Alejandra Rosete Reyes. MD, MSHCA Honorary Chairman: Gilberto Castañeda BSBIO, PhD 16:20 – 16:45 h Gaps in Latin American Region and Transitioning to Excellence in National Pharmacovigilance Systems. Dra. Alejandra Rosete Reyes 16:45 – 17:10 h Good Practices in Pharmacoepidemiology and Pharmacovigilance development. ** Stanley A. Edlavitch, PhD, MA, FACE. Professor of Epidemiology. Department of Psychiatry. UMKC School of Medicine 17:10 – 17:35 h Passive pharmacovigilance in pharmaceutical industry. Achievements and challenges for Mexico. Dr. Luis Felipe Cortes. Member of the Asociaci´n Mexicana de Farmacovigilancia 17:35 – 18:00 h Beyond passive pharmacovigilance: research and education. Dr. Gilberto Castañeda Hernández. Former AMEFAR President 18:00 – 18:20 h Questions and comments **SPONSORED BY THE PHARMACOEPIDEMIOLOGY INTERNATIONAL 18:20 - 18:30 h Coffee break 18:30 - 20:00 h POSTER SESSION 20:00 – 22:00 h Play at the Palace 20:00 - 21:00 h Business meeting of AMEFAR SOCIETY AULA MAGNA OF THE PALACE OF THE SCHOOL OF MEDICINE OF 19 THURSDAY MAY THE 19th, 2011 07:00 - 08:00 h Registration 08:00 - 10:00 h Symposium 17: Arachidonic Acid Metabolism IN HONOR OF DR. JOHN McGIFF MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairmen: Dr. Carlos Castillo Henkel and Dr Pedro López Sánchez 08:00 – 08:10 h Introduction. Bruno Escalante, M.D., Ph.D. 08:10 -08:30 h ―PPARa and Proline Hydroxylase Binding Domains in the regulation of renal function and blood pressure‖ Adebayo Oyekan DVM, PhD. Interim Associate Provost/Associate Vice President for Research. Professor and Director, Center for Cardiovascular Diseases. College of Pharmacy and Health Sciences,Texas Southern 08:30 – 08:50 h Nox Inhibitor Discovery: A Multidisciplinary Approach to Taming the Adventitia‖ Patrick J. Pagano, Ph.D., F.A.H.A. Professor & Graduate Program Director. Department of Pharmacology and Chemical Biology & Vascular Medicine Institute. University of Pittsburgh School of Medicine 08:50 – 09:10 h Experimental Models to study pregnancy pathology. Rosa Amalia Bobadilla MD., PhD. Directora de la Escuela Superior de Medicina del IPN. Instituto Politecnico Nacional, Mexico D.F. 09:10 – 09:50 h Five Decades related to Arachidonic Acid Metabolism. John McGiff MD. New York Medical College. Valhalla NY 09:50 – 10:00 h Questions and comments 08:00 – 10:00 h Symposium 18: Academy - Industry Relationships IN MEMORY OF DR. ROBERTO VARGAS ECHEVERRÍA GRAND HALL (PARANINFO DE LA ESCUELA DE MEDICINA) Chairwoman: Dr. María Dolores Ramírez González, AMEFAR President 08:00 – 08:40 h La vinculación tecnológica en la UNAM. M. en C. Carlos Maynor Salinas Santano. Coordinador del Sistema de Incubadoras INNOVAUNAM 08:40 – 09:10 h Semblanza del Dr. Roberto Vargas Echeverría. Dr. Horacio Vidrio López. Former AMEFAR President 09:10 – 09:50 h Regulación sanitaria para biotecnológicos. Dr. Augusto Bondani Guasti. Incoming President of AMEFAR 20 09:50 – 10:00 h Questions and comments 10:00 - 10:10 h Coffee break 10:10-12:10 h Symposium 19: Nanotechnology in Biomedicine MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Laurence Brunton 10:10 – 10:45 h Logic Gate Nanoparticles: a stable and selective strategy for the delivery of therapeutics. Adah Almutairi, Ph.D. Assistant Professor UCSD School of Pharmacy and Pharmaceutical Sciences 10:45 – 10:50 h Questions 10:50 – 11:25 h Designing degradable MRI contrast agents for enhanced contrast and clearance. Eric Schopf, Ph.D. Postdoctoral Scholar, UCSD School of Pharmacy and Pharmaceutical Sciences 11:25 – 11:30 h Questions 11:30 – 11:55 h Lab-on-a-chip cell sorter for biomedical applications. Jose Morachis, Ph.D. Postdoctoral Scholar, UCSD School of Pharmacy and Pharmaceutical Sciences 11:55 – 12:00 h Questions WESTERN PHARMACOLOGY SOCIETY SPONSORED SYMPOSIUM 10:10 – 12:10 h Symposium 20: New approaches for drug development IN HONOR OF DR. EUGENE BRATOEFF GRAND HALL (PARANINFO DE LA ESCUELA DE MEDICINA) Chairwoman: Dra. Elena Guadalupe Ramírez López, Facultad de Química, Universidad Nacional Autónoma de México Honorary Chairwoman: Dra. María Dolores Ramírez González 10:10 – 10:20 h Remembrance of Eugene Bratoeff. By Dra. Elena Guadalupe Ramírez López. Departamento de Farmacia, Facultad de Química. Universidad Nacional Autónoma de México 10:20 -11:00 h Synthesis of progesterone derivatives for bening prostate hyperplasia and prostate cancer treatment. Dr. Eugene Bratoeff. Departamento de Farmacia, Facultad de Química. Universidad Nacional Autónoma de México 11:00 – 11:30 h Current therapeutic options for anxiety treatment. Dra. Elia Brosla Naranjo Rodríguez, Facultad de Química. Universidad Nacional Autónoma de México 21 11:30 – 12:00 h Medicinal plants and propoleos as sources of active principles. Dr. José Fausto Rivera Cruz. Departamento de Farmacia, Facultad de Química. Universidad Nacional Autónoma de México 12:00 – 12:10 h Questions and comments 12:10 - 12:20 h Coffee break 12:20 - 14:20 h Symposium 21: Immunotherapy of neoplastic diseases MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Andrés E. Castell Rodríguez, Jefe del Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México Honorary Chairman: Dr. Iain L. Buxton 12:20-13:00 h Inmunoterapia: principios y aplicaciones. Dr. Luis Felipe Montaño, Facultad de Medicina, Universidad Nacional Autónoma de México 13:00- 13-40 h Inmunoterapia contra células madre tumorales: Dr. Alejandro García Carrancá, 13:40-14:20 h Inmunoterapia con células dendríticas contra melanoma: Dr. Andrés Castell Rodríguez, Jefe del Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México 12:20 - 14:20 h Symposium 21: Muscular dystrophy GRAND HALL (PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA) IN MEMORY OF DR. HUGO GONZÁLEZ-SERRATOS Chairman: Dr. Alicia Ortega. Biochemistry Professor, Facultad de Medicina, Universidad Nacional Autónoma de México Honorary Chairman: Dr. Iain L. Buxton 12:20 -12:30 h Remembrance of Dr. Hugo González Serratos. Dr. Alicia Ortega. Department of Biochemistry. Facultad de Medicina, Universidad Nacional Autónoma de México 12:30 – 13:10 h Muscular dystrophy: a disease with several pathways towards cell mechanical failure. Dr. Alicia Ortega. Departamento de Bioquímica. Facultad de Medicina. UNAM 13:10- 13:50 h Muscular Dystrophy. A molecular point of view. Dr. Ramón Coral. Department of Biochemistry. Escuela Superior de Medicina, Instituto Politécnico Nacional 13:50-14:00 h Questions and comments 22 14:20 – 16:20 h CONGRESS COURSES 16:20 - 18:20 h Symposium 23: Pharmacovigilance: Active Surveillance MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Abraham Hartzema, Perry A. Foote Eminent Scholar. University of Florida College of Pharmacy Honorary Chairwoman: Dra. María Dolores Ramírez González 16:20 – 16:30 h Overview of active surveillance. **Dr. Abraham Hartzema, the Perry A. Foote Eminent Scholar. University of Florida College of Pharmacy 16:30 – 17:00 h The experience of the Sentinel Project. **Dr. Christopher Delaney. Professor at University of Florida 17:00 – 17:30 h The Observational Medical Outcomes Partnership (OMOP) Experience. **Dr. Abraham Hartzema 17:30 – 18:00 h Mexican experience with postmarketing safety trials. Dr. Luis Felipe Cortés. Member of the Asociación Mexicana de Farmacovigilancia A. C. 18:00 – 18:20 h Questions and comments SPONSORED BY THE PHARMACOEPIDEMIOLOGY 16:20 – 18:20 h INTERNATIONAL SOCIETY OF Symposium 24: Neuronal excitability and GABA IN MEMORY OF DR. SIMÓN BRAILOWSKY GRAND HALL (PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA) Chairman: Dr. Eduardo Calixto González. Head of the Departamento de Neurobiología. Instituo Nacional de Psiquiatría ―Ramón de la Fuente Muñiz‖ Honorary Chairman: Dr. J. Moisés Álvarez Rueda Former AMEFAR President 16:20 – 16:40 h Remembrance of Dr. Simón Brailowsky: the Doctor, the Friend, the Researcher. Dra. Teresa Montiel Montes. Instituto de Fisiología Celular, Universidad Nacional Autónoma de México 16:40 – 17:00 h GABA and memory. Dr. Oscar Galicia Castillo. Departamento de Psicología. Universidad Iberoamericana 17:00 – 17:20 h GABA withdrawal and hipocampal excitability. Dr. César Casasola Castro. Facultad de Psicología, Universidad Nacional Autónoma de México 17:20 – 17:40 h Functional recovery and neuronoglial plasticity. Dra. Angelica 23 Zepeda Rivera. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. 17:40 – 18:00 h Updating the syndrome of GABA withdrawal. Dr. Eduardo Calixto González. . Instituo Nacional de Psiquiatría ―Ramón de la Fuente Muñiz‖ 18:00 – 18:20 h Genetics of sleep. Dr. J. Moisés Álvarez Rueda. Departamento de Psiquiatría y Salud Mental, Facultad de Medicina, Universidad Nacional Autónoma de México 18:20 - 18:30 h Coffee break 18:30 - 20:00 h POSTERS’ EVALUATION SESSION 20:00 - 22:00 h Night tour in Mexico City 20:00 - 21:00 h Presidents’ meeting 24 FRIDAY MAY THE 20th, 2011 07:00 - 08:00 h Registration 8:00-10:00 h Symposium 25: From Traditional Medicine to Scientifc Research on Plants MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dr. Carlos Viesca Treviño Head of the Departamento de Historia y Filosofía de la Medicina, Facultad de Medicina, Universidad Nacional Autónoma de México. 08:00 – 08:20 h Dr. Carlos Viesca Treviño. Head of the Departamento de Historia y Filosofía de la Medicina, Facultad de Medicina, Universidad Nacional Autónoma de México 08:20 – 08:40 H Advances in the knowledge of ―Yoloxóchitl‖. Lic. Carmen Macuil García. Departamento de Historia y Filosofía de la Medicina, Facultad de Medicina, Universidad Nacional Autónoma de México 08:40 – 09:00 h TO BE CONFIRMED 09:00 – 09:25 h Effects of Cacao-derived (-)Epicatechin on Resistance to Fatigue. **Dr. Guillermo Ceballos. Escuela Superior de Medicina, Instituto Politécnico Nacional 09:25 – 09:50 h Antiviral principles from natural sources. Dr. Ricardo Reyes Chilpa. Instituto de Química, Universidad Nacional Autónoma de México 09:50 – 10:00 h Questions and comments **SPONSORED BY DR. LAURENCE BRUNTON 10:00 - 10:10 h Coffee break 10:10 - 12:10 h Symposium 26: Phytomedicaments MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Chairman: Dra. Patricia Yahuaca Mendoza. Profesora Investigadora, Programa Doctorado en Farmacología de la Facultad de Medicina de la Universidad Autónoma de Zacatecas 10:10 – 10:50 h Beginings and fututre of phytomedicaments: development in Mexico..Dr. Javier Lozoya. Director Médico y de Investigación Científica, Genomma Laboratories. Vice-Presidente de la Asociación Mexicana de Fitoterapia A.C. 10:50 – 11:10 h Changing the paradigm in the therapy of primary health care. Dr. Paul Hersch Investigador del Centro INAH-Morelos. Presidente de la Sociedad Mexicana de Fitoterapia Clínica, A.C. 25 11:10 – 11:30 h Development of Integrative Medicine Program in Mexico City. Dr. Ángel González Domínguez. Director de Coordinación y Desarrollo Sectorial, Secretaria de Salud del Distrito Federal 11:35 – 11:55 h Pharmacological Research on phytomedicines in Zacatecas. Dra. Patricia Yahuaca Mendoza. Universidad Autónoma de Zacatecas, México 12:00 – 12:10 h Questions and comments 10:10-10:50 h PLENARY LECTURE: Education Virtual Spaces for Research and GRAND HALL (PARANINFO DE LA ESCUELA DE MEDICINA ) Dra. Georgina Araceli Torres Vargas. Profesora Investigadora del Centro Universitario de Investigaciones Bibliotecológicas, Universidad Nacional Autónoma de México 12:10 - 12:20 h Coffee break 12:20 - 13:20 h PLENARY LECTURE : The impact of RNAi on the pharmaceutical industry MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Dra. Isabel Saad Villegas. General Director BIRREMEDIA S. A. de C. V. 13:20 – 13:30 h Coffee break 13:30 – 14:20 h PLENARY LECTURE: prescription Bioethics of medicaments’ MAIN HALL (AUDITORIO ―DR. GUSTAVO BAZ PRADA‖) Dr. José Vidal Gual 14:20 – 16:20 h CONGRESS COURSES 16:20 - 18:35 h POSTER COMPETITION PRESENTATIONS OF THE NINE FINALISTS 18:35 - 19:00 h Coffee break 19:00 – 19:30 h Presentation of awards: “Kevin Lee Award” for the best presentation on Cancer Research (800 USD) AMEFAR FIRST PLACE AWARDS (15,000 pesos each), Honoring: Dr. Enrique Hong Chong, Dr. Laurence Brunton, and Dr. Horacio Vidrio López AMEFAR SECOND PLACE AWARDS (10,000 pesos each), 26 Honoring “Incoming Bondani Guasti” AMEFAR President” Augusto Recently deceased AMEFAR Former President: “Dr. Roberto Vargas Echeverría” AMEFAR THIRD PLACE AWARDS (5,000 pesos each), Honoring “Past Presidents” J. Moisés Álvarez Rueda, Andrés Navarrete, and Rodolfo Rodríguez Carranza CLOSING CEREMONY 19:30 - 20:30 h Complimentary wine 27 SCHEDULE FOR POSTER PRESENTATIONS 28 29 SCHEDULE FOR POSTER PRESENTATIONS TUESDAY MAY THE 17th 2011. MAIN SQUARE OF THE PALACE OF THE SCHOOL OF MEDICINE TOPICS: Cardiovascular, Endocrine, Gastrointestinal and Respiratory Systems. Metabolic Syndrome and diabetes: NUMBER TITLE AUTHORS 1 Antihypertensive and vasorelaxant effects of a methanol extract and isolated compound from Chiranthodendron pentadactylon (Larreat) in rats Magos Guerrero GA, Lorenzana Jiménez M, Mendiola Almaraz L, Escobar Ramírez JL 2 Effect of angiotensin (1-7) after 24 and 48 hours of myocardial infarction Flores MJ, Valencia HI, Martínez AL 3 Effect of the compound LQM319 and captopril in the contraction produced by angiotensin I and angiotensin II in the presence of angiotensin 1-7 in aortas from spontaneous hypertensive rats Orozco Cortés NV, Hernández Valencia I, Martínez Aguilar L 4 Time-dependent reversal of renal and aortic histological changes in aortic coarctation-induced hypertension in rats López Islas I, Terrón JA 5 Effect of caçao derived (-)epicatechin on mithocondrial swelling induced by myocardial ischemia/reperfussion injury in rats Ortiz Vilchis MP, Rubio Gayosso, Ceballos G, Villareal F 6 Effects of two anesthetic (propofol or ketamine-xylazine) procedures on the heart rate variability, in dogs López Rodriguez M, Ruiz Vega H, Fenton Navarro B, Letechipia Vallejo G, Cervantes M 7 Relaxation changes in the thoracic aorta and coronary arteries in the gene mutant mice SGCD (B6.129 SGCDTM1MCN) Castillo Hernández MC, Castillo Henkel C, De los Santos S, Guevara Balcázar G, Rosas Vargas H, Coral Vázquez RM 8 Contractile changes to angiotensin II in aorta and coronary artery in the gene mutant mice SGCD (B6.129 SGCDTO1MCN) Marin Romero MC, Castillo Hernández MC, Castillo Henkel C, Guevara Balcázar G, Rosas Vargas H, Coral Vázquez RM 9 Modification of the involvement of cyclooxygenase with age in the Castillo Hernández MC, Guevara Balcázar G, Vélez 30 contractile effect of phenylephrine in rat aorta Resendiz JM, López Canales J. Castillo Henkel C. 10 Analysis of the relaxant effect of rosuvastatin lactone in rat aortic rings Polanco Ponce Ana C., López Canales Jorge S.,Pérez Álvarez Víctor M., Castillo Henkel Enrique, P. López Sánchez, Castillo Hernández María del Carmen, Castillo Henkel Carlos 11 (Pro) rennin receptor expression levels when captopril or losartan are administered in nephrectomized rats Cruz Laguna EY, Vargas Robles H, Mendez Tenorio A, Escalante Acosta B 12 Study of the interaction between the adrenergic system and reninangiotensin system at vascular level Sebastian Barajas G, Estevez M, Franco A, Hong E, Villafaña S 13 Cardiovascular disorders in acute myocardial infarction and reperfusion in dog and rabbit. Preliminary study of an antioxidant to prevent recurrence in the course of the disease Raúl E. Cuevas Durán, Patricia Yahuaca Mendoza, Adrián Reyes López y José Luis Alvarado Acosta 14 Angiotensin II increased functional response and vascular hypertrophy indirectly trough α1D-adrenoreceptors in wistar rats Itzell A. Gallardo Ortíz, P. López Sánchez, J.J. López Guerrero, J.D. Sánchez-González, M. Ibarra and R. Villalobos-Molina 15 Pharmacological profile of the dopamine D2-like receptor subtypes mediating inhibition of the sympathetic vasopressor outflow in pithed rats Inna I. Ruiz-Salinas, Abimael González Hernández, Guadalupe Manrique Maldonado, Bruno A. Marichal Cancino, Alain H. Altamirano, Carlos M. Villalón 16 Modifications of functionality of rat aorta β-adrenergic receptors during development López Canales O, López Canales J, Padilla Pérez J, EscalanteAcosta B, Castillo Henkel C 17 Effects of antihypertensive compounds on glucose uptake of isolated cardiomyocytes from hypertensive rats on a high sodium diet R. Carbó, N. Torres, V.Leguízamo R. González Y L. Martínez 18 Long-term effects of medroxiprogesterone on vascular alpha-1 adrenergic receptors in female rat aorta during hipertensión Marian E. Martínez Cruz, Maximiliano Ibarra, J. Javier López Guerrero, Víctor Manuel Farías Rodríguez, Rafael Villalobos Molina 31 19 Effect of captopril pre-hypertensive therapy on both expresión and function of angiotensina II AT1 receptors in SHR kidney Castro Moreno P, López Guerrero JJ, Ibarra Barajas M, Villalobos Molina R 20 Animal model of myocardial fibrosis in the setting of chronic cardiovascular complication of type 2 diabetes mellitus Guadrón Llanos AM, Leal Anguiano AI, Huerta Olvera SG; Vázquez AO, Miranda Díaz AG, Salazar Montes A; Gálvez Gastelum FJ; Rincón Sánchez AR; Islas Carbajal MC 21 Effect of early diabetes on the expression of alpha-1-adrenoreceptors in aorta of Wistar kioto and spontaneously hypertensive rats Rodríguez JE, Reséndiz Albor AA, Arciniega Martínez IM, Campos Rodríguez R, Hong E, Villafaña S 22 Effect of isoproterenol on systolic pressure, heart rate and hypertrophy of young and old mice previously exercised Cano Martínez A, Flores Chávez P, Vargas González A, Nieto Lima B 23 Gastroprotective effect of carbenoxolone and 3αhidroximasticadienonic acid in the model of gastric damage induced by ketorolac in the rat Rojas Zaldívar E, Castañeda Hernández G, Navarrete Castro A, Chávez Piña AE 24 Functional alterations on the contractile response in the guinea-pig ileum induced by several periods of hypoxia and ischemia in vitro Montes de Oca Mejorada M, González Cabañas J, Gómez AC, Santiago Mejía J, Ventura Martínez R 25 Pharmacological evaluation of FL-6, an immunomodulatory drug, in chornic hepatitis induced in wistar rats Osuna Marínez U, Petricevich López VL, Hernández Pando R, Reyes Esparza J, Rodríguez Fragoso L 26 Effect of tlaltipizol on uterine smooth muscle of rat Martínez Enriquez ME, García Delgado AJ, Campos Sepúlveda E 27 Effect of Cu2+, Fe2+, Cr3+, CD2+ and H2O2 on catalytic activity of acetylcholinesterase and acetylcholine in vitro Hernández Rodríguez M, Correa Basurto J, Mendez Garrido A, Rosales Hernández MC 28 Ceramide-phospholipase A2 induced vasoconstriction in the isolated perfused rat kidneys Rocío Bautista-Pérez, Abraham Arellano, Martha Franco, Bruno Escalante. 29 Effects of 17α-ethinylestradiol and 17β-estradiol on coagulation factors in male wistar rats Martínez Maldonado JD, Franco Murillo Y, Jaimez Melgoza R 32 30 Effects of 17-βaminoestrogens on MCF-7 cells proliferation Avila ME, Medina Jiménez M, Lemini C 31 Gender differences in the response to chronic treatment with 17βestradiol and 17β-aminoestrogen pentolame on hemostasis in rats Lemini C, Jaimez R, Medina Jiménez M, Ávila ME 32 Interspecies differences in the ovariectomy recovery of rats and mice of some haemostatic markers Lemini C, Jaimez R, Avila ME, Medina Jiménez M, 33 Effect of chronic restraint stress on 5-HT7 receptor expression in rat adrenal glands García Iglesias BB, Terrón JA 34 Caffeine-induced vascular smooth muscle contraction is modulated by 17β-estradiol in rat aorta Villegas Bedolla, J.C. Godínez Hernández D.; Urquiza Marín H.; Nateras Marín, B.; Hernández Rebollar M; Valencia Hernández I 35 The 5HT7 receptor-mediated meningeal dilatation induced by 5carboxamidotryptamine in rats is not altered by 5-HT depletion and chronic corticosterone treatment E. MARTÍNEZ-GARCÍA, C.SÁNCHEZ-MALDONADO AND J.A. TERRÓN 36 Morpho-histological changes in gonads of rat females treated perinatally with testosterone propionate and coumestrol Ruíz de Chávez Mejía JA, Rosales Torres AM, Herrera Gutiérrez H, Rivero JJ, Ávalos Rodríguez A, Zamora Gutiérrez D, Vergara Onofre M 37 Cell-based and in-silico studies on the high intrinsic activity of two boron-containing salbutamol derivatives at the human beta2adrenoreceptor Soriano-Ursúa MA, McNaught Flores D, Nieto Alamilla G, Correa Basurto J, Trujillo Ferrrara JG, Arias Montaño JA 38 Non-quantal release of acetylcholine in guinea pig airways: Role of choline transporter Chávez Alderete J, Vargas Becerra MH, Cruz Valderrama JE, Montaño Ramírez LM 39 PPADS a P2x receptor antagonist, a novel inhibitor of the reverse mode of the Na+/Ca2+ exchanger in guinea pig airway smooth muscle Reyes-García J, Flores-Soto E, Cruz Valderrama JE, Sommer B, Barajas- López C, Montaño LM 40 The role of the serotonin in pulmonary vascular hyperreactivity during diabetes mellitus López-López GC, Atonal-Flores F, León Palacios A, Flores Hernández J, Flores Guerrero J.L, Pérez Vizcaíno F 33 41 Effect of sibutramine on 5-HIAA levels and select oxidative biomarkers on female rat brain regions in presence of zinc Calderón-Guzmán D, Hernández García E, Barragán Mejía G, Juárez Olguín H, Buendía Soto E, Trujillo Jiménez F, Santamaria del Angel D, Carmona Aparicio L 42 Effect of sibutramine and L-carnitine on the levels of 5-HIAA and GSH in the brain regions of rat with low normal protein diets Calderón-Guzmán D, Hernández García E, Trujillo Jiménez F, Juárez Olguin H, Barragán Mejía G, Pierdant Rioja FJ, Tena Betancourt E, Herrera Pérez J 43 Characterization of renal nitric oxide and reactive oxygen species production in obese mice Ramírez Alejandra, Vargas Robles H, Escalante B, Ríos A 44 Time course of the diabetogenic activity of streptozotocin in rat Aguilar-Mariscal H, Rodríguez Vázquez T, Martínez Hernández A, Blé Castillo JL, Tovilla Zárate CA, Patiño Camacho SI, Aguilar Marisacl I, Bermúdez Ocaña DY 45 Streptozotocin sensitivity in the adult wistar rat Rodríguez Vázquez T, Aguilar Mariscal H, Pérez Meza JA, Juárez Rojo IE, Blé Castillo JL, Bautista Escalante CT, Patiño Camacho SI, Aguilar Mariscal I 46 Early obesity potentiates development of renal failure: Role of nitric oxide pathway and oxidative stress Gámez Méndez A, Vargas Robles H, Arellano Mendoza M, Ríos A, Escalante B 47 Plants used as antidiabetic remedy in La Chontalpa, Tabasco, México Aguliar Mariscal H, Guemez Ortiz KC, Pérez López G, Huerto Cortés J, Méndez Córdoba E, Noriega Constantino MD, Bautista Escalante CT, Aguilar Mariscal I 48 Leaf hidromethanolic extract of Stuthanthus venetus (BLUME) attenuates the metabolic syndrome induced by high fructose diet in wistar rats Lorenzana Jimenez M, Magos Guerrero GA, Mendiola Almaraz L, Maldonado J, Gijón Granados E, González García X 49 Effect of captopril and losartan on the early alterations of diabetic nephropathy Núñez Ortíz R, Vázquez Cruz B, Segura Cobos D, Amato Martínez D, López Sánchez P 50 Changes in the vascular response to angiotensina II in a model of gestacional diabetes Tufiño C, Villafaña S, Hernández M 34 51 Role of gestational diabetes in the vascular response to phenylephrine Tufiño C, Farnández Vallin E, Bobadilla RA 52 Comparison of clinical improvement produced by carbamazepine or diclofenac sodium in patients with diabetic neuropathy Tinoco Samos AE, Córdova Pérez N, Arenas Tellez JM, Ordoñez Librado JL 53 Effect of several doses of streptozotocin on blood sugar in male CD1 mice Ventura J, Aguilar CN, Ramos R, Campos E, Alarcón F 54 Flaxseed oil supplement to spontaneously hypertensive rats (SHR) with diabetes: effect on blood glucose, blood pressure, cholesterol and triglycerides Pérez-Hernández I.H., Mejía-Zepeda R 55 Study of 2,4- dimethoxycinnamic acid as a possible hypocholesterolemiant agent Pastor O, Santiago J, Wong C 56 Beneficial effects on glucose homeostasis after oral administration of Morinda panamensis in normoglycemic rats Vargas-Castillo Ariana Elizabeth, Castillo-Kauil Alejandro, Lara-Riegos Julio César, Ortiz-Andrade Rolffy Rubén 57 Glycation and glycosylation of serum cholinesterase in diabetic mice treated with glycine Salinas Arreortua N, Alarcón Aguilar FJ, Gómez Olivares JL 58 Metformin increases paraoxonase (PON) activity in obese subjects Sierra Vargas MP, Meaney A, Meaney E, Ceballos G 59 Effect of the infusion of Morinda citrifolia L. (Noni) on the clinical course of diabetes mellitus induced with aloxan Del Bosque de la Barrera F, Galván Morales D, García Ruiz M, García Saucedo B, Miranda Torres A, Rangel Suárez G, Fregoso Padilla M, Barrera Escorcia E, Velasco Lezama R 60 Up regulation of mRNA of 5HT3 receptor in taste bud from rats with experimental diabetes mellitus Salgado Chávez MA, Mercado Camargo R 61 Expression of RANm of tryptophan hydroxylase in taste buds of the rat circumvallate papilla Juárez Múñoz BE, Mercado Camargo R 62 Biomarkers: Expression of sphingomyelinase and ceremidase in serum and kidney of diabetic rats Abraham Arellano, Martha Franco, Rocío Bautista-Pérez. 35 63 Sphingosine 1-phosphate-induced vasoconstriction is increased in the isolated perfused kidneys of diabetic rats Israel Coronel, Abraham Arellano, Horacio Osorio, Martha Franco, Rocío Bautista-Pérez 64 Effect of ursodeoxycholic acid on oxidative stress and SGLT2 expression in the kidney of diabetic rats Horacio Osorio, Israel Coronel, Abraham Arellano, Martha Franco, Bruno Escalante and Rocío Bautista 65 Hypoglycemic effect of aqueous extract of Carica papaya leaf in streptzotocin-induced diabetic rats Juárez-Rojo IE, Miranda-Osorio PH, Ramón-Frías T, AguilarMariscal H, Blé-Castillo JL, Rodríguez-Hernández A, DíazZagoya JC, Bermúdez-Ocaña DY 66 Endothelium dysfunction in the diabetic rat is reverted for insulin in vitro López-López G , León Palacios A , Atonal-Flores F , 1 3 Hernández Cabrera J , Flores Guerrero J.L 67 Gender differences in the induction of type 2 diabetes with a streptozotocin-nicatinamide model Alonso-González Sonia Areli, Márquez-Flores Yazmín Karina, Martínez-Galero Elizdath, Meléndez-Camargo María Estela 68 Effect of selective COX-2 inhibitor and CCK antagonist in diabetic rats De la O-De la O E , Mandujano-Morales JA , Juárez-Rojo 1 2 3 IE , Ortega-Varela F , Tovilla-Zárate CA , Jiménez-Santos 3 2 4 A , Aguilar-Mariscal H , Flores-Murrieta FJ , BermúdezOcaña DY 69 Antiobestity effect of resveratrol in an experimental model of dietinduced obestity in rats Escobedo-Moratilla A., Vargas-Morales JM., Pérez-Urizar J 70 A diet rich in polyunsaturated fatty acids prevents the metabolic disorder caused by type 1 diabetes Franco-Colín M., Servín-Santos J. E., and Cano Europa E. 71 Inosine effect of insulin signaling in C9 hepatic cells: Molecular mechanism Arellano Plancarte A, Villalobos Molina R 72 Effects of metformin on the differentiation of adipocyte stem cells Luz María Mejia-Cristobal, Roxana Carbo-Zabala, Gabriela Cosio-Garcia, Jorge Melendez-Zajgla, Vilma MaldonadoLagunas, Laura del Bosque-Plata 1,2 1 3 3 1 36 73 Effect of chronic sugar intake on malnourishment-induced behavioural, metabolic and cardiovascular adaptation Vargas-Olivos A, Reyes Antunez E, Ramírez Solares R, Mendiola Alcaraz L, Ramírez Oseguera R, Ramírez González MD 37 SCHEDULE FOR POSTER PRESENTATIONS WEDNESDAY MAY THE 18th 2011 TOPICS: Central Nervous System, Pharmacoepidemiology, Pharmacovigilance, Pharmacokinetics NUMBER TITLE AUTHORS 1 Locomotor effects of nanoparticles containing levopopa on a MPTP-induced Parkinson’s disease model Soriano-Ursúa MA, Aguilar Faisal L, Jiménez Estada I, Ocampo López JO, Trujillo Ferrara JG 2 Acute toxicity and effects on mouse locomotor activity of a new dopamine boron containing compound designed by using in silico tools Soriano-Ursúa MA, Correa Basurto J, Padilla Martínez I, Dominguez Campos A, Ocampo Mendoza K, Ocampo López JO, Trujillo Ferrara JG 3 Synthesis, characterization and acute toxicity studies of an arylethanolamine derivative with sedative properties López-Cabrera Y, Leal Gutiérrez MA, Lascari Jiménez EC, Correa Basurto J, Trujillo Ferrara JG, Soriano Ursúa MA 4 Valproic acid modulates brain plasticity through epigenetic chromatin remodeling in the blind rat: implications for human sight recovery Fetter Pruneda I, Olivos Cisneros L, Díaz D, Padilla Cortés P, Báez Saldaña A, Gutiérrez Ospina G 5 Sex differences in experimental anxiety in middle age rats: effects of diazepam Olvera Hernández S, Fernández-Guasti A 6 Paradoxical response in the elevated plus maze model in rats: effect of diazepam administration Saldívar González JA, Fiesco Roa MO, Campos Rodríguez UE 7 Excitatory role of 5HT7 receptor in the trigemino vascular system of the rat: relevance to migraine Martínez García E, Leopoldo M, Lacivita E, Terrón JA 8 Nitric oxide promotes the recovery of cognitive deficit in an experimental model of cholinergic damage Hernández Melesio MA, Quevedo Corona L, Jiménez Capdeville ME, Santoyo Pérez ME, Gelista-Herrera N, González Esquivel D, Sánchez Mendoza A, Ríos C, Pérez Severiano F 38 9 Antioxidant activity of topiramate: an antiepileptic agent Cárdenas Rodríguez N, Coballase Urrutia E, Huerta Gertrudis B, García Cruz ME 10 Effects of implantation of TIO2-DA complex in the caudate nucleus attenuates motor abnormalities in the 6-hydroxydopamine model of hemi-parkinsonism Vergara Aragón P, Domínguez Marrufo LE, Ibarra Guerrero P, Hernández Ramírez H, Hernández Tellez B, López Martínez IE, Sánchez Cervantes I, Zepeda Rodríguez A, García Macedo JA, Valverde Aguilar G 11 Effects of bee products on open field, lipid peroxidation levels and performance of seizures kindled by administration of pentylenetetrazol in rats Zarraga Galindo N, Vergara Aragon P, Ibarra Guerrero I, Dominguez Marrufo LE, Hernádez Ramírez H, Hernádez Telllez B, López Martínez IE, Sánchez Cervantes I 12 Role of the 5-HT6 receptor in the stress response and its cognitive implications Briones Aranda A, Ossio R, Quirarte GL, Prado-Alcalá RA 13 Administration of 25-35 of amyloid beta fraction over expression of heat shock proteins and sites of glycosylation in cells C6 Calvillo M, Espinosa B, Zenteno E, Guevara J 14 Neonatal monosodium glutamate administration decrease amphetamine induced locomotor activity susceptibility effects in adult mice Campos Sepúlveda E, Martínez Enriquez ME, López Cabrera M, Saldívar González JA 15 Cognitive deficit induced by acute cerebral ischemia in the elevated-plus maze performance Alejo Martínez A, González Ríos J, Parra Gámez L, Santiago Mejía J, Ventura Martínez R, Gómez C 16 Striatal protection in NNOS knock-out mice after quin-induced oxidative damage: relationship with huntingtin expression Gerónimo Olvera C, Heras Romero Y, Tristán López L, Osorio cruz Y, González Esquivel D, Ríos C, Pérez Severiano F 17 DL-3-hydroxy-3-ethyl-3-phenyl propionamide (DL-HEPP) possible GABAA receptor modulator Meza Toledo SE, Bowery NG 18 DL-3-hydroxy-3-ethyl-3-(3’-trifluormethylphenyl) butyramide, a new anticonvulsant Cervantes Espinoza JG, Peralta Cruz J, Meza Toledo SE, 39 19 Effects of MGLUR5 antagonist MTEP on hippocampal epileptic afterdischarges in immature rats Zavala Tecuapetla C, Mares P, Kubova H 20 Modification of plasma biomarkers and imaging of mild cognitive impairment in elderly by Ginko biloba Navarro Pineda D, Uribe Hernández A, Olivares Corichi IM, Jiménez Zamarripa CA, Londaíz Gómez R, Calzada Mendoza CC 21 Opioid receptor distribution in human cortex of patients with mesial temporal lobe epilepsy Christian L Frías-Soria, Mario Alonso-Vanegas, José M Cisneros Franco, Cecilia Zavala-Tecuapetla, Luisa Rocha 22 Neuroprotective effect of lovastatin in vivo modelo of MPP+ in Parkinson disease Aguirre-Vidal Yoshajandith, Montes Sergio, Ríos Camilo, TristanLópez 23 Antidepressant-like effect of Ginkgo biloba extract (EGB 761) in the mouse forced swimming test: role of oxidative stress Norma Serrano-García, Patricia Rojas, Omar N. MedinaCampos, José Pedraza-Chaverri, Sven O. Ögren, Carolina Rojas, Elizabeth Ruiz-Sánchez, Pedro Montes del Carmen 24 S-allycysteine protects against 1-methyl-4-phenylpyridiniuminduced parkinsonism in mice Patricia Rojas, Norma Serrano-García, Omar N. MedinaCampos, José Pedraza-Chaverri, Perla D. Maldonado , Elizabeth Ruiz-Sánchez, Pedro Montes del Carmen 25 Perinatal food deprivation interferes with the maternal aggression pattern and NADPH-diaphorase positive neurons of the lactating rat Pérez Torrero E, Hernández Urbiola MI, Silva Barrón CI 26 Neuroprotective effect of simvastatin in an excitotoxic model induced by quinolinic acid Anaya-Ramos Laura, Tristan-López Luis, Monroy-Noyola Antonio, González-Esquivel Dinora, Pineda-Olvera Benjamin, Ríos Camilo, Pérez-Severiano Francisca 27 Antioxidant effect of the methanolic extract of Buddleja cordata in rat MPP+ model of Parkinson disease Pérez Barrón Gabriela Alejandra, García Bores Ana María, Rubio Osornio Moisés, Ávila Guillermo, Montes Sergio, Ríos Castañeda Camilo, Monroy Noyola Antonio 28 Short and long-term evaluation of the neuroprotective effects of progesterone on the pyramidal neuron population of the Aguilar-Hernández A, Espinosa-García C, Monfil T, Cervantes M, Moralí G 40 hippocampal CA1 subfield after global cerebral ischemia in rats 29 Insulin effects on isolation calls of infant guinea pigs Zarco de Coronado I, Coronado Zarco IA, Coronado Zarco R 30 Discriminative properties of amphetamine and modafinil Argüelles Hernández R, Mendoza Meléndez MAG, Pinzón Estrada E, López Cabrera 31 Neuropathology of schizophrenia Tristán-Agundis MF, Manzanarez-Colin MC, Villeda-Hernández J, Palacios-Escalona S, Peralta-Rodríguez B, CastañedaGonzáles C, Rembao-Bojórquez D 32 5HT2 and 5HT3 receptors participate in the antinociceptive synergism induced by tramadol plus caffeine Díaz Reval MI, Carrillo Munguía N, Martínez Casas M, López Muñoz FJ 33 Role of the glutamatergic transmission in the sexual exhaustion phenomenon of male rats Córdova-Moreno R, Rodríguez-Manzo G 34 Neurodevelopmental alterations in a post-mortem case of schizophrenia Totxo-Guerrero Daniel Sebastián, Herrera-de la Fuente Roberto, Reyes-Pérez Mariela, Rocha L, Manzanarez-Colin Mariel Carolina, Rembao-Bojórquez Daniel, Peralta-Rodríguez Brenda, Gelista-Herrera Noemí, Tristán-Agundis Ma. Francisca 35 Effect of monosodic glutamate and ketamine in motivated behavior in male mice Córdova-Moreno S., Martínez M. T., Hernández L. L. F., Soto P. C. A., Moreno B. C., Delgadillo G. H. J 36 Cellular damage markers in the temporal lobe of a patient with Dyke-Davidoff-Masson syndrome Villeda-Hernández J., Alonso-Vanegas MA, Osorio-Rico L 37 Evaluation of 3-mercaptopropionic acid induced seizures in wistarkyoto and wistar rats Bañuelos-Cabrera I, Orozco-Sánchez S. Rocha L.L 38 Resolution and anticonvulsant activity of the enantiomers of DLHEPP Cervantes-Espinoza José, Buendía-Pazaran José G, De la Cruz-Marín Amelia, Vargas-Fernández Eugenia, Peralta-Cruz Javier, Chamorro-Cevallos Germán, Meza-Toledo Sergio E 41 39 Gait dynamics analysis evaluates hindlimb revascularization Ríos A, Delgado A, Escalante B, Santana J 40 Cognitive impairment in rats after unilateral 6-OHDA lesion in thalamic reticular nucleus Chuc-Meza E, Avila-Velarde G., Guarneros-Bañuelos E., Miranda-Rivera O., Limón D., García-Ramírez M 41 Plasma levels of clozapine and norclozapine in Mexican schizophrenia patients Castro Nelly, González Esquivel D, Custodio V, Rojas Tomé S, Jung H 42 Neurodevelopmental disorders in Alzheimer’s disease. Report of 5 cases Palacios-Escalona S, Manzanarez-Colin MC, Villeda-Hernández J, Totxo-Guerrero DS, Peralta-Rodríguez B, Gelista Herrera N, Orozco S, Rocha L, Castañeda-González C, Reza Garduño Treviño H Rembao-Bojórquez D, Tristán-Agundis MF 43 Fluoride exposure increase carrageenan-induced inflammation and mechanical hyperalgesia in rats and these effects are not reversed by diclofenac Dibildox-Alvarado E., Aguirre-Bañuelos, P. 44 Revesratrol increase anti-inflammatory and analgesic effects of diclofenaco in rats Ortiz-Padilla SA. , Medina-Sifuentes AM. , Aguirre Bañuelos P 45 Antiallodynic effect of meloxicam and proglumide in diabetic neuropathy Bermúdez-Ocaña DY , Suarez-Méndez S , Tovilla-Zárate CA , 2 1 4 Ramos-Domínguez R , Ramón-Frías T , Díaz-Zagoya JC , 5 Granados-Soto V , Juárez-Rojo IE 46 Extracellular levels of excitatory and inhibitory neurotransmitters are modified by intracerebral repetitive administration of penicillinG: An in vivo microdialysis study Carmona-Aparicio Liliana , Martínez-Cervantes Adrián , and Rocha Luisa 47 Intracerebral administration of penicillin-G modifies benzodiazepine, Mu-opioid and muscarinic receptors binding in rat brain: An autoradiography study Carmona-Aparicio Liliana , Martínez-Cervantes Adrián , and Rocha Luisa 48 Synergistic antinociception between lysine clonixinate and morphine in the rat formalin test Palomino-González G., Pérez-Urizar J., Aguirre-Bañuelos P 2 1 1,3 2 1 2 1,3 2 42 49 Anticonvulsant drugs, oxidative stress and nitric oxide Vega Rasgado L, Ceballos Reyes G, Vega Díaz F 50 Neuroprotective effect of metallothionein II in cerebral ischemia in a modelo f middle cerebral artery oclussion (MCAo) with reperfusion in rats Vacio Adame Martha Patricia , Díaz Ruíz Araceli , Ortiz Plata 3 2 Alma , Ríos Catañeda Camilo, Monroy Noyola Antonio 51 Analgesic efficacy of tramadol plus lysine clonixinate versus tramadol alone in post-surgical dental pain: A randomized controlled trial J. Pérez-Urizar , I. Torres-Roque , A. Pozos-Guillén , R. 3 4 4 Martínez-Rider , G. Aguilera-Suárez , M. Gómez-Sánchez 52 Preclinical basis for the development of a new analgesic combination: Tramadol plus lysine clonixinate J. Pérez-Urizar , I. Torres-Roque , E. Dibildox-Alvarado , A. 2 3 Torres-Roque , A. Escobedo-Moratilla, G. Aguilera-Suárez , M. 3 Gómez-Sánchez 53 Resinferatoxin inhibit pro-inflammatory cytokines and nitric oxide in model of lipopolysaccharide-induced inflammation O. Gutiérrez-Coronado ,J.L. Muños Carrillo , M.S Luevanos 1 1 1 Raymundo , M.L. Miranda-Beltran , P.T. Villalobos-Gutierrez 54 Antiinflammatory action of capsaicin on the brain endotoxinchallenged mice M.S Luevanos Raymundo , P.T. Villalobos-Gutierrez M .M.L. 1 1 Miranda-Beltran ,.O. Gutiérrez-Coronado 55 Prevalence of chronic diseases and polypharmacy in elderly patients attending a dental frist level of attention Barrueco Noriega Guadalupe Sara , Suarez Guerrero Ivonne , Rodríguez García Rosalía 56 Pharmacoepidemiological study about the use of methylphenidate in a group of patients with attention-deficit and hyperactivity disorder Gómez Galicia DL, Rodríguez Fragoso L, López Aymes G, Sánchez Alemán M, Reyes Esparza J 57 Pharmacoepidemiology of psychoactive medication in adult patients in the psychiatric department of Durango General Hospital Edgar Cano-Torres, Ismael Lares- Asseff, Martha Sosa-Macías, Carlos Salas, Alberto Allegre-Alonso, Carlos Galaviz-Hernández, Alexis Lares López, Verónica Loera C 58 Medical prescription and its application after establishing pharmacological vigilance system under the internal medicine speciality Hospital General Dr Miguel Silva Mejía Sánchez A, Rodríguez Barrón A 59 Ageing, health and medicinal consumption in a sample of Izazola Conde C, Montes de Oca Zavala V, Santiago E 1 2 1 2 1 3 2 1 1 1 1 1 1 2 43 academic employees at a Mexican university 60 Ocular and systemic adverse effects of ophthalmic and non ophthalmic medication: a systematic review Izazola Conde C, Zamora de la Cruz D, Tenorio Guajardo G 61 Pharmacokinetics of pioglitazone in a population with type 2 diabetes mellitus exposed to high concentrations of arsenic in Peñón Blanco, Durango Terrones-Gurrola R, Vértiz-Hernández A, Ibarra-Cázares A, Ramírez Flores E, Camacho-Luis A, Lozano- Guzmán E, SalasPacheco J, López-Guzmán O 62 Pharmacoepidemiology of headache in a university population of Mexico Escobedo-Moratilla A., Fragoso-Morales L., Pérez-Urizar J 63 Pharmacoepidemiology use of antihypertensive drugs, 2011 Alba Leonel A, Molina Guarneros JA, Carvajal García-Pando A 64 Administration of gentamicin using pharmacokinetic parameters Quiñonez Palacio G 65 Development and validation of a liquid chromatography method to quantify midazolam in a new oral formulation for pediatric use Chávez Pacheco JL, López Aviña B, Flores Pérez J, Sandoval Ramírez E, Juarez Olguin H, Ramírez Mendiola B, González Zamora J, Changin Guerra A, Flores Pérez C 66 Effect of exercise on serum BDNF levels in school children Ríos-Badillo V*., García-Arenas G, Goytia-Acevedo R., Maravilla A, Meza-Velazquez R., de Villa D 67 Population pharmacokinetics of cyclosporine in the early periodo of post renal transplant (RT) in pediatric recipients Ismael Lares-Asseff, Samuel Saltzman, J. David Urbina Álvarez, Gabriela Guillé P., Martha Sosa M., Verónica Loera C., Carlos Galaviz H., Alejandra Toledo 68 Changes during development in the transient kinetics of the reactivity of rat aorta to phenylephrine Javier Padilla-Pérez, Carlos Castillo-Henkel, Ma. Carmen Castillo-Hernández 69 Pharmacokinetics and bioaviability of pioglitazone in mexicans with diabetes mellitus type 2: Pilot study Ibarra Cázeres AE, Frías Zepeda E, Ramírez Flores E, Salas Pacheco JM, López Guzmán OL, Lozano Guzmán E, Vértiz Hernández AA 70 Relationship among changes in hematocrit, albúmina and corticosteroid dose on the disposition of tacrolimus during the first Robles Piedras AL, Domínguez Ramírez A, Romano Moreno S, 44 six months after renal transplantation Fuentes Noriega I, Mancilla Urrea E, González López EH 71 Pharmacokinetics variations of acetaminophen in acute renal failure rats Fallas JM, Mélendez ME 72 Pharmacokinetic interaction of vincristine and prednisone in murine model Claudia Araceli Reyes-Estrada, Patricia Yahuaca-Mendoza 73 Aminoglycosides: Therapeutics, ototoxicity and mitocondrial hypersensitivity of genetic origin Nadia Magali Torres-Ruíz, Aurora Castañeda-Arroyo, Omar Granados and Graciela Meza 74 Pharmacokinetics variations of acetaminophen in acute renal failure rats Fallas JM, Mélendez ME 75 In vitro delivery study of diclofenac and natural sesquiterpene (C15 H18 O2) formulated in a nanostructures anhydra emulsion Vázquez ML, Calpena AC, García ML, Garduño ML ,Flórez P 76 Pre-transplant mycophenolate mofetil pharmacokinetics in mexican children Villa M, González R, García-Roca P, Hernández AM, Ortiz L, Castañeda-Hernández G, Medeiros M 77 Pharmacokinetics of lidocaine and its metabolite as hepatic function marker in dog BE Pérez-Guillé , F Villegas-Alvarez , A Toledo-López , MA 1 1 4 Jiménez-Bravo , JF González-Zamora , MC Carrasco-Portugal , 4,5 1 FJ. Flores-Murrieta , RE Soriano-Rosales 78 The quality of compounded solid dosage forms containing carbamazepine: A bioequivalence study in healthy volunteers Estela Dibildox , Aurigena Antunes de Araújo , Lílian Grace da 2 3 Silva Solon , Gerlane Bernardo Coelho Guerra , Dulce 1,4 1 4 Cordero , Abraham Escobedo , Irma Torres-Roque , Amador 5 Covarrubias , José Pérez-Urizar 79 Release of nystatin nanoemulsions versus reference formulation Fernández, F; Mallandrich, M; Clares, B; Lazaro, R; Flo, A; Calpena AC 80 Pharmacokinetics of oral dicloxacillin in mexican volunteers J.C. Aguilar Carrasco , A. Galicia-Gutiérrez , M.C. Carrasco2 Portugal and F.J. Flores Murrieta 1,2 1 3 2,3 1 1 45 SCHEDULE FOR POSTER PRESENTATIONS THURSDAY MAY THE 19th 2011 TOPICS: Medicinal Plants, Toxicology, Education in Pharmacology, Cancer NUMBER TITLE AUTHORS 1 Ethnobotanic study of Randia aculeata in the municipality of Jamapa, Veracruz, México Gallardo Casas CA, Mercado Hernández C, Valadez Omaña MT, Valenzuela Vargas MT, Castillo Henkel C, Castillo Hernández MC 2 Cysticidal activity of extracts from some plants used as antiparasitic plants in the folk medicine Palomares Alonso F, Rojas Tomé S, Juárez Rocha V, Rufino González Y, Palencia Hernández G, Jung H 3 Alterations produced by an extracto f Rosemarnius Officinalis L on the contraction induced by KCL and electrical stimulation Rivero Osorno O, Montes de Oca Mejorada M, González Trujano ME, Gómez AC, Ventura-Martínez R 4 Heimia salicifolia contains alkaloids with vasorelaxant effect Vázquez Cruz B, Guzmán Hernández E, Avila Acevedo JG, Segura Cobos D 5 Essays of biological activity and secondary metabolites search of Justicia spicigera Gómez Verján JC, Aguilar Laurents MI, Reyes Chilpa R, Magos Guerrero GA 6 Antimicrobial screening of Justicia spicigera schltdl Vega Avila E, Tapia Aguilar R, González Gutiérrez AM, Ramírez Cruz A, Ramírez J, Velasco Lezama R 7 Hibiscus (Hibiscus sabdariffa) calñyces extracts exhibits antipyretic activity Fenton Navarro B, Velázquez Hernández ME, Nateras Marín B, Rodríguez Barrón A, Torner Aguilar L, Ruiz Vega H 8 Compound detection and toxicity evaluation of organic extract of the Erythrina coralloides Castañeda Antonio D, Rosales Herrera J.M., Blas Castillo J. Hernández Aldana F., Jiménez Salgado T., Tapia Hernández A 9 Total phenolic content and antioxidant activity of Cercidium praecox Aburto Amar R 46 10 Effect of the decocotion of Urtica dioica on the proliferation in vitro of hematopoietic cells from anemic and healthy mice Herrera Solis S, Tapia Aguilar R, Flores Sáez JL, Vega Ávila E, Santana Carrillo J, Velasco Lezama R 11 Neuropharmacological profile and toxicity of ethanolic extract of Rhodiola rosea L Montiel Ruiz RM, Roa Coria JE, Patiño Camacho SI, Déciga Campos M 12 Antioxidant activity of Tlanchalagua (Erythrea tetramera schiede) Camacho Luis A, Esteban Méndez M, Araujo Contreras JM, Ávila Rodríguez H, Vértiz Hernández A 13 Linalol the antidepressant principle of Litsea galucescens (Mexican Bay) essential oil Guzmán-Gutiérrez S. L.ª, Gómez-Cansino R.ª, Pérez-Flores, b F. J.ª, García-Zebadúa J.C.ª, Jiménez-Pérez, N. , ReyesChilpa R 14 Ganoderma lucidum reduce the kainic acid-induced hippocampal neurons damage via inflammatory cytokines and GFAP expression in rats Aguirre-Moreno AC., Campos-Peña V ., Villeda-Hernández b a J ., León I 15 Pythochemical analysis of the natural juice of Kalanchoe gastonis bonneri and Kalanchoe flammea with human sperm agglutination and immobilization Fajardo Peregrina S, Miranda Beltrán ML, Huacuja Ruiz L 16 Chemical and histopathologic analysis of the effect of the mixture of seven plants (EHAM7) in a model of experimental cirrhosis Miranda Beltrán ML, Soria Fregozo C, Gutiérrez Coronado O, Rosales Muñoz CG, López velázquez AL, Treviiño Ortiz R, Huacuja Ruíz L 17 Evaluation of total phenolic content and antioxidant activity of Malva parviflora L Marañón Ruiz V.F, Herrera de la Torre JD, Almanza Orozco R. Miranda Beltrán ML. Aparicio Fernández X, Chiu Zarate R 18 Bioactivity-guide isolation of hypoglycemic constituents of Ibervillea sonorae (S. WATSON) green roots collected in Cumirpa-Porvenir, Sonora, Mexico Angel Jardón Delgado, Mariano Martínez Vázquez and Gil Alfonso Magos Guerrero 19 Comparative study of antibacterial activity in vitro of two varieties of Urtica dioica Rafaela Tapia Aguilar, Ana María González Gutiérrez, Alma Delia Ramírez Cruz, Abigail Aguilar Contreras, Rodolfo Velasco Lezama b 47 20 Hematopoietic activity of Urtica dioica in vitro Rafaela Tapia Aguilar, Alma Delia Ramírez Cruz, Ana María González Gutiérrez, Abigail Aguilar Contreras, Rodolfo Velasco Lezama 21 Anti-inflammatory effect of Senna villosa chloroform extract and (8hydroxymethylen)-trieicosanyl acetate, in a skin inflammation model Susunaga Notario Ana del Carmen, Almanza Pérez Julio César, Zavala Sánchez Miguel Angel, Pérez Gutiérrez Salud, Román Ramos Rubén, Alarcón Aguilar Francisco Javier 22 CRATAEGUS OXYACANTHA PREVENTS OXIDATIVE DAMAGE AND UNCLOUPLING OF GAP JUNCTION INTERCELLULAR COMMUNICATION IN EXPERIMENTAL LIVER CIRRHOSIS INDUCED BY ETHANOL Lorena Ávila-Carrasco, José Luis Alvarado-Acosta, Rosalinda Gutiérrez-Hernández and Patricia YahuacaMendoza. 23 EFFECT OF ETHANOL EXTRACT FROM Calea urticifolia (Mill.) DC. ON THE REGULATION OF INFLAMMATION MEDIATED BY ADIPONECTIN Guzmán, P. ; Soto-Peña G. ; Cárdenas, N. ; GarcíaChávez, E 24 EXPERIMENTAL ASSESSMENT OF ANTIINFLAMMATORY EFFECT OF Hamelia patens Jacq. AND Calea urticifolia Mill (DC Guzmán, P ; García-Chávez, E. ; Soto-Peña, G. ; Juárez, B 25 Anti-Helicobacter pylori anti-ulcerogenic and anti-edematogenic activities of Cyrtocarpa procera Wendy Itzel Escobedo-Hinojosa, Karina García Martínez, and Irma Romero 26 Assessment ethanolic extract of Calea urticifolia Mill DC on blood glucose and lipids in healthy rats fed a high fat diet Ortiz-Segura, M.C and E. García-Chávez 27 Antioxidant activity of Rosmarinus officinalis in the prevention of experimental alcoholic Sonia Sifuentes-Franco Rosalinda Gutiérrez-Hernández and Patricia Yahuaca-Mendoza 28 Oxydative stress in a murine hyperglycemic model modulated by Rosmarinus officinalis Fátima E. Del Muro-Casas, José Luis Alvarado-Acosta y Patricia Yahuaca-Mendoza 29 Relationship between oxidative stress and glycosylated hemoglobin-A1 in diabetes mellitus induced by streptozotocin and treated with Rosmarinus officinalis Sandra Carrillo Ibarra, José Luis Alvarado-Acosta, Claudia A. Reyes-Estrada y Patricia Yahuaca-Mendoza 1 1 2 2 2, 2 2 48 a 30 Anti-Helicobacter pylori and gastroprotective activities of aqueous extracto of Cuphea aequipetala (Lythraceae) Juan Francisco Palacios-Espinosa , Guillermo Garcíaa b b Valencia , Robert Bye , Edelmira Linares , and Irma Romero 31 The ethanolic extract of Trichaptum biforme presents antinociceptive and anxiolytic properties López-Galindo G, Hernández -García A., Ortiz-Butrón R., Cortés-Mercado V., and Cano-Europa E 32 Long-lasting effects in adult (12 months old) cerebellar cortex of mice exposed in utero to diazepam Márquez Orozco A, De la Fuente Juárez G, Gasca Ramírez MV, Márquez Orozco MC 33 Dimorphism in sexual behavior of CD-1 mice prenatally treated with diazepam Hernández Álvarez LAI, Márquez Orozco A, Márquez Orozco MC 34 Sperm morphology of mice prenatally exposed to diazepam Hernández Álvarez LAI, Martínez vargas A, Márquez Orozco A, Márquez Orozco MC 35 Midazolam induces histological alterations in cerebellar cortex of Mouse from p8 to p15 days old Márquez Orozco MC, De la Fuente Juárez G, Gasca Ramírez MV, Márquez Orozco A 36 Antifungal drugs do not alter the infectivity of S scheckii Sabanero López M, Loza Manjarrez G, Flores Villavicencio LL, Palomino Torres N, Sandoval Bernal G 37 A reliable method of liquid chromatography for the quantification of acetaminophen and identification of N-acetyl-p-benzoquinoneimine (NAPQI), its toxic metabolite Flores Pérez C, Chávez Pacheco JL, Equiarte Sólomon F, Ramírez Mendiola B, Rivera Espinosa L, Juarez Olguin H, Flores Pérez J 38 Morphohistological changes in male rat gonads perinatally treated with tamoxifen and coumestrol Zamora Gutiérrez Diana, Rosales Torres Ana María, Vergara Onofre Marcela, Herrera Gutiérrez Héctor, Ávalos Rodríguez Alejandro 39 Primary and secondary hidatidosis by Echinococcus granulosus modulation of the cellular atmosphere to remain by long seasons of time, a challenge for the therapeutic one Mondragón de la Peña MC, Blancas Mosqueda M, Leandro Alvarez RD, Orta García ST, Tavizón García JP 40 Relationship of bone mineral density with the nitric oxide levels as a marker of oxide-reductive stress and the effect of the treatment for CÓRDOVA-PÉREZ N, BASURTO-ACEVEDO L , VÁZQUEZ 1 2 2 MARTÍNEZ AM , ORDOÑEZ JL , ARENAS-TÉLLEZ JM , 1 49 1 osteoporosis ZÁRATE-TREVIÑO A 41 Comparative study of antioxidants in the prevention of acute hepatptoxicity induced by carbon tetrachloride in murine model Rosalinda Gutiérrez-Hernández, José Luis Alvarado-Acosta, Sonia Sifuentes-Franco, José Luis Martínez-Rodríguez y Patricia Yahuaca-Mendoza 42 Hypothyroidism protects against aniline caused-sleen damage and oxidative stress Hernández-Alvarado J., Rodríguez-Sánchez, R., OrtizButrón, R., Blas-Valdivia, V., and Cano-Europa, E 43 Palmitone prevents PTZ-cuased oxidative stress and cellular damage in brain Hernández-García, A., González-Trujano M. E ., Cano1 Europa, E 44 Phycobiliproteins and C-phycocyanin of Spirulina maxima protect against HgCl2-caused oxidative stress and cellular damage in the kidney Ortiz-Butrón R., Blas-Valdivia V., Rodríguez-Sánchez R., and Cano-Europa E 45 Assessment of apoptosis of mononuclear cells incubated with camptothecin comparison of three methods Gómez-Montalvo A, García-Arenas G, Meza R, GoytiaAcevedo RC 46 Prescription for antibiotics, new legislation in Mexico Espinosa-Meléndez M.T , Medrano-Morales J. , Saracho2 Alarcón A, Alvarez de la C.C 47 Impact of the pharmacist in the health team: improvement of prescription for diabetic and hypertensive patients Mino D, Capellá D , Reyes H , Jasso L , Doubova SV 48 Learning components and scholar achievement in Pharmacology: It´s impact in medical graduate examination Contreras Chaires E, Castañeda S 49 Bioethical analysis of clinical research that is carried out by the pharmaceutical industry in Mexico Martínez Rodríguez G, Álvarez MA, Campos-Sepúlveda AE 50 Academic practice by pharmaceutics chemistry students at the metropolitan autonomous university, Xochimilco Delgadillo Gutierrez HJ, Moreno Bonett C, Zugazagoitia Herranz R, Sánchez Martínez C, Córdova Moreno R 51 Validation of certain reagents of evaluation in biochemistry and molecular biology at the faculty of medicine, UNAM Saldaña Balmori Y, Delgadillo Gutiérrez HJ 2 1 2 2 3 4 5 50 52 Evaluation of learning of carbohydrates as source of energy in the cell Delgadillo Gutiérrez HJ, Saldaña Balmori Y 53 Criteria on which professors and students of odontology faculty from UNAM based their drug prescription R Guzmám Alvarez, M Medeiros Domingo, AE Campos Sepúlveda, LI Reyes Lagunes 54 Presentation of the degree in Pharmacy (New Curriculum of studies 2008, Superior Studies, Cuautitlán, UNAM) Degree: Bachelor in Pharmacy Suemi Rodríguez Romo, Margarita Flores Zepeda, Arturo Aguirre Gómez, Patricia Jeane Domínguez Quiñones 55 OMNIALVA software and biomedical research equipment Ortega Martínez N, Hernández Alva A 56 Molecular modeling applied to study consequences of plymorphisms in ligand recognition of human B1 and B2 adrenoreceptors Ciprés Flores FJ, Soriano Ursúa MA, Amezcua Gutiérrez MA, Trujillo Ferrera JG, Correa Basurto J 57 Search immunogenic epitopes of neuroaminidase from H1N1 influenza A by computational tools Reyes Loyola Paola Kinara, Correa Basurto Jose, Miguel Quiliano Meza, Verónica Briz, Mª Angeles Muñoz-Fernández, Luis Esteban Tolentino López, Mirko Peralta Zimic 58 Docking studies of phenol derivatives as inhibitors of angiotensin converting enzyme (ACE) Vázquez VH, Alemán MA, Abrego VH, Acuña J, Velázquez AM, Martínez L, Camacho B, López Castañares R, Angeles E 59 Pharmacological modulation of the renin-angiotensin system by mathematical modeling Pérez Rosas NC, Rodríguez González JG 60 In silico drug design of oseltamivir derivatives against pandemic influenza A H1N1 (2009) Tolentino Lopez LE , Peralta Zimic M, Quiliano Meza M, Briz M, Muñoz-Fernández MA, Padilla Martínez II, Reyes Loyola P, Martínez Ramos F, López,G, Trujillo Ferrara J, Correa Basurto J 61 Molecular docking and inhibition studies in Entamoeba histolytica Hexokinase Saucedo-Mendiola María Letícia, Salas-Pacheco José 3 1,4 Manuel , Avitia-Domínguez Claudia , Araujo-Conteras 1 1 Jesús , Ávila-Rodríguez Armando , Ávila-Rodríguez 1 1 Humberto , Téllez-Valencia Alfredo 62 Evaluation of cysticidal activity of new derivates of 5(6)-carboxamides Juárez Rocha V, Palomares Alonso F, Hernández LF, 51 of carbendazim Palencia Hernández G, Jung Cook H 63 Cyclic nucleotide-gated channels participate on the capability of fertilization of mammalian sperm Cisneros A, Sánchez D 64 Analysis of the expression of cytochrome P450 in the skeletal striated muscle Dora Molina-Ortiz , Araceli Vences-Mejía , Rafael Camacho2 1 Carranza , José González- Zamora , Oscar Colín1 2 Martínez , Javier Espinosa-Aguirre 65 Calmodulin antagonists inhibit the sea urchin sperm hyperpolarization necessary for directed movement towards the egg Galindo BE 66 MDR1 exon 12 gene polymorphism in renal transplant donors and its relationship to transplant outcome Garcia-Roca P, Rodriguez-Espino B, Hernández AM, Ortiz L, Medeiros M 67 Effect of auranofin on Taenia crassiceps cysticerci survival and GSH/GSSG ratio Martínez-González, José de Jesús; Miguel Enrique CuéllarMendoza, Omar Huerta-Herrera e Irene Patricia del Arenal Mena 68 In vitro and in vivo trypanocidal activity of the benzyl and ethyl esters of N-propyl oxamate on two different Trypanosoma cruzi strains Aguirre Alvarado Ch*, Rodriguez Páez L*, Baeza Ramírez I*, Nogueda Torres B**, Wong Ramírez C 69 Effect in vitro and in vivo of the ethylester of N-butyl oxamate on the fertility of mouse spermatozoa Cordero-Martínez, J*., Wong, C y Rodríguez-Páez L 70 Studies on the pharmaceutical stability of a nanocarrier system with antineoplastic and immunoregulatory properties intended for the treatment of cervical cancer Acosta Gutierrez J, Juárez López R, Vargas Medellin J, Velasco Lomas I, Rangel Corona R, Weiss-Steider B, Soto Vázquez R, Corona Ortega T 71 Nanopharmaceutical technology for immunoregulatory purposes Corona Ortega T, Weiss-Steider B, Soto Vázquez R, Rangel Corona R 72 Participation of angiogenic factors in the morphology of leiomyoma derived from human uterus Guerrero Zepeda MA, Becerril Montes A, Cárdenas Jaramillo LM, Ocharán Hernández ME, Mota Morales A, Calzada Mendoza CC 1 1 52 73 Synthesis of the cholestane glycoside (25R) -3B, 16B diacetoxy 22 oxocholest-5-en-26-yl B-Dglucopyranoside and its anticáncer properties on cervicouterine cell lines Alvarado Sansininea JJ, Torres Pineda DB, Fernández Herrera MA, López Muñoz H, Hernández Vázquez JMV, López Dávila M, Escobar Sánchez ML, Pinto MB, Sandoval Ramírez J, Sánchez Sánchez L 74 Synthesis of the rinvanil and its antiproliferative and apoptotic properties on cervical cancer cell lines Alvarado Sansininea JJ, Luviano Jardón A, Hernández Vázquez JMV, López Muñoz H, Escobar Sánchez ML, Weiss-Steider B, Regla I, Sánchez Sánchez L 75 Metallodrugs with antineoplasic activity of binuclear heteroleptic PT (II) and PD(II) complexes Andreu-de-Riquer GA, Urquieta Velázquez A, Mendoza MA, Ruiz Azuara L, Sabanero López M, García de la Rosa LA 76 Modification of cadherins expresión in murine melanoma model by daphnetin Jiménez Orozco FA, Rico Urbina VH, Jiménez Trejo F, García Mondragón MJ, Maldonado Espinoza A, Herrera Henriquez MA, Mendoza Patiño N, Mandoki JJ 77 Determination of antiproliferative activity and HDAC inhibitory activity of a series of isoindolines-2-substituted from alpha-aminoacids Trejo Muñoz CR, Mancilla Percino T, Mera Jiménez E, Trujillo Ferrara JG 78 The enantiomers +(-)catechin and –(-)epicatechin induce apoptosis and modulate genes methylation in breast cancer cells lines García Sánchez JR, Hernández Martínez M, Ceballos Reyes GM, Sierra VargasMP, Olivares Corichi IM 79 Biological activity of organometallics cuprum complexes on MDA-MB 231, HELA and Pc-3 cells Vilchis MR, Escutia CD, Pérez BE, Romero RA, Abrego RVH, Vázquez VH, Velázquez SM, Angeles E, Ordaz Pichardo C 80 Cytotoxic and no mutagenic activity of novel heterocyclic compounds in human cervical cell lines Frías González S, Escutia Calzada D, Abrego Reyes VH, Angeles Anguiano E, Romero Rojas A, Ordaz Pichardo C 81 Evaluation of antitumoral activity of some Kalanchoe sp extracts in various cancer cell lines and their genotoxicity Arias González I,(investigador) Licona Flores EA, Burgueño Tapia E, Arriaga Alba M, Ordaz Pichardo C 82 Palliative treatment with morphine drug subcutaneously in patients with cancer of Palia Institute of Guadalajara, Jalisco Luna-Hernández AL, Alvizar-Medina AM, Valenzuela-Limón OL, García-Montalvo EA, García-Llamas E Escutia-Gutiérrez R, López-López JG y Herrera-Huerta EV 53 83 Synthesis, antineoplastic activity and structure-activity relationships of novel 5N-sustituted diazabicyclic amides of phenylacetylricinoleic acid Luviano A, Aguiñiga I, Tiburcio R, Demare P, López M, Monsalvo I, Santiago E, Regla I 84 TUMORAL MARKERS IN LYMPHOMA INDUCED BY 7,12DIMETHYL-BENZ[A]ANTHRACENE IN RAT AS A MODEL TO STUDY ANTI-TUMOR AGENTS Laura E. Marquez-Delgado, Claudia A. Reyes-Estrada y Patricia Yahuaca-Mendoza. 85 HEPATOPROTECTION AND TUMORAL MARKERS MODULATED BY CRATAEGUS OXYACANTHA ANTIOXIDATIVE EFFECT IN EXPERIMENTAL ALCOHOLIC LIVER CIRRHOSIS José Luis Martínez-Rodríguez, Rosalinda GutiérrezHernández y Patricia Yahuaca-Mendoza 86 Anti-neoplastic effect of L-ornithine analogues in vitro Medina-Enríquez, Miriam-Marlene*; Velázquez-Ortiz, IndraVictoria*; Alcántara-Farfán, Verónica*; Aguilar-Faisal, Leopoldo**; Trujillo-Ferrara, José Guadalupe***; RodríguezPáez, Lorena I 87 Effect of Uncaria tomentosa in breast cancer induced by 7,12dimethylbenz[A] anthracene Manuel de Jesús Gallegos-Saucedo, Patricia YahuacaMendoza, Rosalinda Gutiérrez-Hernández y José Luis Alvarado-Acosta 88 Extracts from Sargassum hystrix buxifolium chauvin, have antitumor effect and also cell cycle arrest in cervical cancer cells Luna-Cruz Norma A, Mendoza-Rodríguez Yolanda, Luna1 Nophal Angelica, Rubio-García Ricardo , Ávila-Ortiz 1 Alejandrina Graciela , Corona-Ortega T, Weiss.Steider B y Rangel-Corona R 89 Antitumoral effect of ―Hierba del câncer‖ (Prunella vulgaris) in leukemia L5178Y in mice CD-1 G. Almaguer-Vargas ; J. R. Montejano-Rodríguez; E.G. Olvera Hernández; M. Bautista-Avila; H. Cortés-López; E. Ramírez Contreras 90 Validation of an experimentañ method to induce chronic hyperglycemia by only one dose of streptozotocim (STZ) in Wistar rats José L. Figueroa-Hernández 1,2 José L. Figueroa Espitia1, Gabriela Fernández Saavedra1 Teresa Ramírez2 and Mariano Martínez Vázquez 2 91 Wild flora present in a new urban human settlement at Xochimilco in Mexico City Figueroa-Hernández J.L., Fernández-Saavedra G. and Figueroa-Espitia J.L 1 54 55 ABSTRACTS OF POSTER PRESENTATIONS LISTED IN ALPHABETICAL ORDER BY AUTHORS’ NAME 56 57 TOTAL PHENOLIC CONTENT AND ANTIOXIDANT ACTIVITY OF CERCIDIUM PRAECOX Rola Aburto Amar, Universidad de la Cañada, Teotitlán, Oaxaca, México There is evidence that suggests a correlation between the antioxidant activity of plant phenolic compounds and the prevention from such diseases as cardiovascular diseases, 1,2 certain cancers and several other age-related degenerative disorders . Although traditional 3 Mexican medicine utilizes approximately 5000 plants , most of these species have not been evaluated as sources of natural phenolic antioxidants. The aim of this study was to determine the total phenolic content (TPC) and the total antioxidant capacity (TAC) of the methanolic extract of the flowers of Mantecoso (Cercidium praecox), a plant used in Mexican folk medicine. Plant material was collected in Oaxaca, Mexico, and extracted by standard 5 maceration process. The TPC was determined using the Folin-Ciocalteau micro method , and was expressed as gallic acid equivalents (GAE) in mg per g of dry extract. The TAC was 6 determined using the Cupric Ion Reducing/Antioxidant Power Assay (CUPRAC) , and was expressed as trolox® equivalents (TE) in mg/ per g of dry extract. A Green tea (Camellia sinensis) sample were purchased from an ordinary shop and subjected to the same 7 processes, since it is one of the richest sources of natural phenolic antioxidants .The TPC values of C. praecox and C. sinensis were 52.1 ± 1.6 and 229.3 ± 5.1 mg GAE/g of dry extract, respectively. Their TAC values were 1.37 ± 0.21 and 3.83 ± 0.46 TE/g of dry extract, respectively.The demonstration of the antioxidant activity and the phenolic content of C. praecox contribute to validate its traditional medicinal use. Although Mantecoso has lower TPC and TAC values than Green tea, it represents an interesting regional source of natural phenolic antioxidants, since the latter is barely consumed in non urban zones. STUDIES ON THE PHARMACEUTICAL STABILITY OF A NANOCARRIER SYSTEM WITH ANTINEOPLASTIC AND IMMUNOREGULATORY PROPERTIES INTENDED FOR THE 1 1 TREATMENT OF CERVICAL CANCER. Acosta Gutierrez J ., Juárez López R ., Vargas 1 1 2 2 1 Medellín J ., Velasco Lomas I ., Rangel-Corona R ., Weiss-Steider B ., Soto Vázquez R ., 2 Corona Ortega T . Laboratorio de Tecnología Farmacéutica (1) y Laboratorio de Oncología Celular (2). FES-Zaragoza. UNAM. E-mail: [email protected]. The lymphocyte growth factor Interleukin 2 (IL-2) has proven to be effective in the therapy against human tumors by activating the immune system, in particular the cytolytic Tlymphocytes (CTLs) and killer cells. Nevertheless, the systemic delivery of IL-2 has been limited by its high toxicity. In this respect nanoparticles constitute an interesting tool for in situ IL-2 delivery. Our work group has shown that several cervical cancer cells express, like lymphocytes, the IL-2 receptor (IL-2R) on their membranes. Recently we have reported the construction of a nanocarrier structure that expresses non-covalently bound IL-2 on its external surface that renders the particle susceptible to be attached to IL-2R-bearing cells. In order to evaluate the stability of our IL-2 nanocarrier particles, their physical integrity in different conditions of temperature, light and pH was determined using a cytometer for particle size and complexity. Our results demonstrated that the nanocarrier presented a suitable stability as long as the buffering system (pH) stayed under control. (Grant: ICYT PIUTE 10-100). 58 PHARMACOKINETICS OF ORAL DICLOXACILLIN IN MEXICAN VOLUNTEERS. J.C. 1 1 2 2,3 Aguilar Carrasco , A. Galicia-Gutiérrez , M.C. Carrasco-Portugal and F.J. Flores Murrieta . 1. Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, SSA; 2. Instituto Nacional de Enfermedades Respiratorias Ismael Cossío Villegas, SSA; 3. Escuela Superior de Medicina, IPN. Dicloxacillin is a semi-synthetic penicillin that is widely used to treat a wide variety of bacterial infections including pneumonia, infections of the urinary tract and skin. Currently, the reports about its pharmacokinetic information in humans are very scarce. The purpose of this study was to characterize the oral pharmacokinetics of dicloxacillin in Mexican female volunteers. Eighteen female healthy volunteers aged 24.58 ± 0.86 years, weighing 59.85 ± 1.18 kg, and of 158.13 ± 1.28 cm height were volunteered for participation in this study. All volunteers were fit according to medical history, medical examination and suitable laboratory tests. The volunteers read the protocol approved by the institutional ethics and research committees and gave written informed consent for participation. After an overnight fast the volunteers received an oral dose of 500 mg of dicloxacillin and plasma samples were obtained at selected times during a 6 hours period and stored frozen at -80°C. Plasma levels of the drug were determined using a high performance liquid chromatographic method developed in our laboratory and pharmacokinetic parameters were obtained by non-compartmental approach. Parameters values were (mean ± s.e.m.): Cmax 25.91 ± 1.35 µg/mL, tmax 0.96 ± 0.16 h, AUC 43.58 ± 1.52 µg.h/ml and t1/2 0.83 ± 0.08 h. These results indicate that dicloxacilline is quickly absorbed and it has a short half-life, which is according to some previous reports. PLANTS USED AS ANTIDIABETIC REMEDY IN “LA CHONTALPA”, TABASCO, MÉXICO. 1 1 1 1 Aguilar-Mariscal H , Guemez-Ortiz KC , Pérez-López G , Huerto-Cortés J , Méndez-Córdova 1 1 1 2 1 E , Noriega-Constantino MD , Bautista-Escalante CT , Aguilar-Mariscal I . Universidad 2 Juárez Autónoma de Tabasco. Villahermosa, Tab. México. Facultad de Biología. UAEM. Cuernavaca, Mor. México. ([email protected]) The use of traditional medicinal remedies and plants in the treatment of type-2 diabetes is an important aspect of health treatment and the same time reduces financial burden. The aim of the present research was to collect and to perform the botanical identification of the plants empirically used for diabetes control in La Chontalpa community, in Tabasco, México. One herbalist and twelve diabetic patients were interviewed and they mainly mentioned the use of 12 plants for control diabetes. Bibliographic review was made on line to complete the pharmacological information. The plants were botanically identified for a biologist as: Allium satirum (ajo); Matricaria recutita (manzanilla); Azadirachta indica A.Juss (neem); Allium cep L. (cebolla); Artemisia ludoniciana (esencio verde); Morinda citrifolia (noni); Ananas comosus (L) Merr (piña); Bixa orellana (achiote); Arnica montana (arnica); Momordica charantia (cundeamor); Tabebuia rosea (bertol) DC (macuili); Eupatorium petiolare (amargocilla, cuasia). Other plants were mentioned for a great diversity of uses medicinal. The information on line indicated that these plants may be used for diabetes control too. These plants were: Capraria biflora L (claudiosa); Lactuca sativa L (lechuga); Opuntia ficus-indica (nopal); Zea mays (pelo de maíz); Lochnera rosea (L) Reichenb (vicaria); Aloe vera (sábila). This study was supported by PFICA (UJAT-2009-CO5-05) 59 TIME COURSE OF THE DIABETOGENIC ACTIVITY OF STREPTOZOTOCIN IN RAT. 1 1 1 1 Aguilar-Mariscal H , Rodríguez-Vázquez T , Martínez-Hernández A , Blé-Castillo JL , Tovilla1 2 3 1 1 Zárate CA , Patiño-Camacho SI , Aguilar-Mariscal I , Bermúdez-Ocaña DY . Universidad 2 Juárez Autónoma de Tabasco. Villahermosa, Tab. México. Escuela Superior de Medicina 3 IPN. México DF. Facultad de Biología. UAEM. Cuernavaca, Mor. México. ([email protected]) A commonly used method to induce insulin-dependent diabetes in rodents is a single dose injection (i.p.) of streptozotocin (STZ). We investigated the diabetogenic effect of STZ in the rat at 0 day and 1, 30, 60 and 90 days post-administration of STZ (50 mg/kg, i.p.). Male Wistar rats aged 14 weeks (weight range, 300-350 g) were used. Diabetes was confirmed one day after injection by measurement of tail vein blood glucose levels (>250 mg/dL). Thirty, 60 and 90 days after STZ injection, glycemia was again determined. STZ, but not saline injection caused hyperglycemia. The blood glucose level measured in these rats was greater than 250 mg/dL one day after STZ injection. During the following 90 days, the blood glucose levels were maintained above of 250 mg/dL in diabetic but not in non-diabetic rats. In addition, rats treated with STZ did not gain weight (-20%) compared to those treated with saline. Our data suggest that the changes in the levels of blood glucose and body weight are depend of time and diabetes-induced STZ is a good model animal that it may be used for chronic studies. This study was supported by PFICA (UJAT-2009-CO5-05). SHORT- AND LONG-TERM EVALUATION OF THE NEUROPROTECTIVE EFFECTS OF PROGESTERONE ON THE PYRAMIDAL NEURON POPULATION OF THE HIPPOCAMPAL CA1 SUBFIELD AFTER GLOBAL CEREBRAL ISCHEMIA IN RATS. 1 1 1 2 1 1 Aguilar-Hernández A , Espinosa-García C , Monfil T , Cervantes M , *Moralí G . Unidad de 2 Investigación Médica en Farmacología, CMN Siglo XXI, IMSS. México DF. Facultad de Ciencias Médicas y Biológicas ―Dr. Ignacio Chávez‖, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán; MEXICO Global cerebral ischemia (GCI) can lead to the death of selectively vulnerable neurons like the CA1 pyramidal neurons of the hippocampus, as a consequence of progressive cellular processes evolving as short- or long-term patterns of neuronal damage after ischemia. Progesterone (P4) has shown to preserve the functional integrity of the hippocampus in spite of a severe long-term (90 days) loss of the pyramidal neuron population at CA1, and to prevent the progression of functional deficits after ischemia. The aim of this study was to compare the CA1 pyramidal neuron population at 28 or 97 days after GCI, under treatment with P4 or its vehicle, to assess possible differences in the progression of neuronal damage after ischemia. Three groups of adult male rats were used: Sham, subjected to surgical maneuvres; Isch+Veh, subjected to GCI (20 min) by the four-vessel occlusion model (4-VO) and treated with vehicle; Isch+P4, subjected to GCI (20 min) by 4-VO and treated with P4 (8 mg/kg, IV) at 15 min, 2, 6, 24, 48 and 72 h post-ischemia. No differences were found at 28 vs 97 days in the CA1 pyramidal neuron population of the Sham group. A severe pyramidal neuron loss was observed at CA1 in the Isch+Veh group being higher at 97 vs 28 days after ischemia (37 and 14% remaining neurons respectively, as compared to the Sham). A severe neuronal loss (15 and 25% remaining neurons respectively), was also observed in Isch+P 4 rats. The results suggest a progression of neuronal damage at CA1 in the absence of neuroprotective treatment after 28 days post-ischemia, and confirm previous observations that the functional integrity of the hippocampus may be preserved in P4- but not in Vehtreated rats, in spite of a severe neuronal loss in CA1. 60 IN VITRO AND IN VIVO TRYPANOCIDAL ACTIVITY OF THE BENZYL AND ETHYL ESTERS OF N-PROPYL OXAMATE ON TWO DIFFERENT TRYPANOSOMA CRUZI STRAINS. Aguirre Alvarado Ch*, Rodriguez Páez L*, Baeza Ramírez I*, Nogueda Torres B**, Wong Ramírez C*. Departamentos de Bioquímica* y Parasitología**, ENCB-IPN. Prolongación Carpio y Plan de Ayala, C.P. 11340, México D.F. e-mail: [email protected]. Tel. 57296000ext 62321. Trypanosoma cruzi is the etiologic agent of Chagas´ disease. The T. cruzi α-HADH isozyme II (HADH) is involved in the parasite energy metabolism and it has been demonstrated that selective inhibitors of HADH show trypanocidal activity. It was reported that N-propyl oxamate (NPOx) was inhibitor of HADH, however due to its polarity it cannot diffuse through the parasite membrane to exert the trypanocidal effect. Therefore in this investigation we evaluated the trypanocidal effect of ethyl and benzyl esters of NPOx (NPOx-Et and NPOx-B respectively). Both compounds were evaluated on the activity of the T. cruzi HADH using a homogenate of T. cruzi, where carboxyl-esterases are also present, the NPOx-B and NPOxEt inhibited T. cruzi HADH in similar way than NPOx, it indicated that NPOx is the true inhibitor of T. cruzi HADH. Then we evaluated the in vitro effect of NPOx-B on the circulating trypomastigotes of the NINOA strain, which was proportional to the concentration of this substance, reaching 100% of death with 8 mM concentration. On the contrary the INC-5 strain was less susceptible to the action of these compounds. Similar results were obtained with NPOx-B on cultured epimastigotes of both strains. In comparison the NPOx-Et showed lesser in vitro trypanocidal activity than NPOx-B. Besides the NPOx-B showed higher activity + on depletion of intracellular concentrations of NAD and ATP in comparison with NPOx-Et. These results demonstrate that the trypanocidal activity of these oxamates is a consequence of the energy metabolism decrease of this parasite. Thereafter, in vivo trypanocidal activity of NPOx-B on parasitaemia and amastigote nests was greater than NPOx-Et on NINOA or INC5 acute infected mice. This agrees with the NPOx-B hydrophobicity that allows it to cross biological barriers. The results obtained suggest that NPOx-B could be used as a prodrug to the Chagas's disease. GANODERMA LUCIDUM REDUCE THE KAINIC ACID–INDUCED HIPPOCAMPAL NEURONS DAMAGE VIA INFLAMMATORY CYTOKINES AND GFAP EXPRESSION IN a b b a a RATS. Aguirre-Moreno AC ., Campos-Peña V ., Villeda-Hernández J ., León I . Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos Laboratorio de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología, MVS, SSA. Introduction: Ganoderma lucidum is a basidiomycete fungus that is used in traditional Chinese medicine. Polysaccharide and triterpene are two major categories of compounds purified of this species, which are attributed to its potent biological activity. Studies have indicated that components of these extracts have a wide range of pharmacological actions including to the Central Nervous System. Purpose: In this work we analyze whether Ganoderma lucidum has a protective effect in the hippocampus of rats treated with kainic acid and if this response is correlated with a reduction in inflammatory cytokine tumor necrosis factor- (TNF-), Interleukin 1ß (IL1ß) expression, and further reduction in astrocytes activation (glial fibrillary acidic protein expression). Material and methods: Rats (5) were administered with GL (10mg/kg i.p) or vehicle (distillated water), thirty min after was injected kainic acid (KA) (5 mg/kg). Twenty four hours after the animals were transcardially perfused and their brain collected for histological and histochemical purposes. Results: The hippocampal tissue from KA injected animals (5 mg/kg) showed a significant degree of cell damage in the dentate gyrus and CA3, extensive cell loss, atypical neurons with unusual cytoskeletal inclusions, piknotic nuclei and shrunken cytoplasmic, edema at neuropil, enhanced immunorectivities to GFAP, expression of TNF- and IL1ß was observed. The treatment of rats with GL (10 mg/kg) before to KA significantly prevented all these markers. Conclusions: Our results shows that GL protect against KA induced alterations of hippocampal cells and confirm the efficacy of the treatment, are an effective experimental tool to reduce the brain lesions associated with inflammatory responses. 61 + NEUROPROTECTIVE EFFECT OF LOVASTATIN IN VIVO MODEL OF MPP IN 1 2 2 PARKINSON'S DISEASE Aguirre-Vidal Yoshajandith , Montes Sergio , Ríos Camilo , 2 1 1 2 Tristan-López Luis , Monroy-Noyola Antonio . Facultad de Farmacia UAEM. Departamento de Neuroquímica INNN. Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of pigmented dopaminergic neurons in the substantia nigra pars compacta with subsequent striatal dopamine (DA) deficiency and increased lipid peroxidation in substantia nigra. The etiology of the disease is still unclear, and it is thought that PD may be caused by a combination of genetic and environmental factors. In the search of new pharmacological options, statines have been recognized for their potential application in neurodegenerative disease. The aim of this work is to characterize the neuroprotective effect of lovastatine in a + model of PD induced with 1-methyl-4-phenylpyridinium (MPP ). Male Wistar rats (200-250 g; n = 6/group) were divided in 4 groups and treated for 7 days depending on the experimental + group. Control group(C) and MPP group (M) received 0.5mL/kg of DMSO i.p. Lovastatine group (L) and Lovastatine/MPP+ group (LM) were treated with 5mg/Kg of lovastatine i.p. On day 7 the groups M and LM received an intraestriatal injection of MPP+ (15µg/8µL) and saline for the groups C and LM. Six days after inducing damage, the circling behavior induced by apomorphine (1 mg/kg S.C.) was assessed and 24 hrs later rats were sacrificed by decapitation and the striatum was dissected and stored at -70°C until HPLC analysis. Lovastatin administration diminishes significantly the turns counting (54%) when compared to the M group (p<0.05), this neuroprotection was corroborated comparing the DA levels between both groups. PHARMACOEPIDEMIOLOGY USE OF ANTIHYPERTENSIVE DRUGS, 2011. 2 3 1 Alba Leonel A., 1 Molina Guarneros J. A, Carvajal García-Pando A ; Alumna Ph.D. in Health Sciences "Epidemiology‖ and Professor of the School of Nursing and Midwifery and 2 School of Medicine, UNAM, Tutor and Professor in the Faculty of Medicine, UNAM, Mexico 3 City, Cotutor and Professor of Pharmacoepidemiology Institute, University of Valladolid, Spain. E mail: [email protected] The worldwide prevalence of hypertension (HTA) in adults is 20-25% and of these 70% live in developing countries. In Mexico, the HTA held the ninth leading cause of death in 2002, with a rate of 10.38 per 100, 000. It is the first per capita consumer of drugs in Latin America, with sales growth of 13% (2000- 2005). The HTA is a public health problem, and is a disorder where the patient must wear a life-long treatment, so it is necessary to identify and monitor the use of drugs to improve the quality of prescribing, and as taking into account the limited public resources and the continuous increase of drug costs. ¿To determine the patterns of use of antihypertensive drugs and their impact on the patient? The evaluation of the use of antihypertensive drugs allows us to make more efficient investment spending, increase effectiveness and reduce damage in patients with the aim of improving the quality of life of hypertensive patients. The health system must implement programs that improve the quality of care at a lower economic cost, and that hypertension has an impact on mortality in Mexico and worldwide. A study of drug utilization with a crossover design in three different times (2000, 2005 and 2010). The target population will be patients with hypertension outpatient and inpatient at a hospital in Mexico City. A questionnaire was designed on purpose (general data, factors that determine or influence the prescription number and type of medication). The pharmacoepidemiology is a useful tool to learn how drugs are used to contribute to a more rational use and reduce the damage caused to patients. 62 COGNITIVE DEFICIT INDUCED BY ACUTE CEREBRAL ISCHEMIA IN THE ELEVATED1 2 PLUS MAZE PERFORMANCE ALEJO-MARTÍNEZ A , GONZÁLEZ-RÍOS J , PARRA2 1 1 1 1 GAMEZ L , SANTIAGO-MEJÍA J , VENTURA-MARTÍNEZ R , GÓMEZ C . DEPARTMENT 2 OF PHARMACOLOGY, DEPARTMENT OF ANATOMY, FACULTY OF MEDICINE, NATIONAL UNIVERSITY OF MEXICO. Stroke is the third leading cause of death in major industrialized countries, and the first cause of motor disability and cognitive deficit. Cerebral ischemia induces a wide range of clinic manifestations, such as motor incoordination, sensory, cognitive and behavioral deficits, which prevent patients to continue with their normal life style. Bilateral sequential common carotid artery sectioning (SCAS) is a model developed in our laboratory; that produces a reproducible pattern of mortality, extensive brain damage and a wide range of measurable neurobehavioral alterations. Thus, the aims of this work were to identify and describe alterations in learning and memory induced by SCAS on the elevated plus maze (EPM) performance and to evaluate the neuroprotective efficacy of dexrazoxane in reducing cognitive deficit. For that purpose we used male CFW middle-aged (40-60 weeks), mice were randomly assigned to three different groups: SCAS, sham or control group. For the cognitive evaluation we used a modification to the procedure proposed by Itoh et al (1990), i.e., we calculated the average of the right choices made by mice during the testing session. Briefly, mice were trained (4 consecutive days) to enter the reinforced arm, which was reinforced with a drop of sweetened milk. All animals performed three trials per session, before (basal), and 24, 48, 72 and 96 h after surgery. Our results showed that ischemic animals slept and groom more than sham animals after the surgery. Second surgery reduced the SCAS group performance at 24 h and 48 h compared with the first surgery which did not modify the performance, namely, SCAS performance average did not reach the criterion along the acquisition phase since most of the SCAS animals were not able to achieve more than the 85% of right choices through the experiment compared with control group. ANTITUMORAL EFFECT OF “HIERBA DEL CANCER” (PRUNELLA VULGARIS) IN 1 LEUKEMIA L5178Y, IN MICE CD-1. G. Almaguer-Vargas ; J. R. Montejano-Rodríguez; E.G. Olvera Hernández; M. Bautista-Avila; H. Cortés-López; E. Ramírez Contreras. UAEH, ICSa. Academic área Pharmacy, Exhacienda Concepción s/n, Tilcuautla road, Hidalgo México. Cancer is a group of diseases with high incidence national and World wide. In 2008, the mortality rate in México took the third place. Most of the time the treatment for Cancer, is very expensive, sometimes toxic, and inefficient. Moreover, is necessary to do research in more antitumor cancer cases and to use medicinal plants in the process as the ―hierba del cancer‖ (Prunella vulgaris). These medicinal plants are frequently used in a traditionally way. The aim of the present research was to prove the antitumor effect of the ―hierba del cancer‖ as oral etanolic extract. The plant was recollected from de Hidalgo state. In this study were created two groups: One group was for control and the other one was for treatment. Each one with 10 mice. The extract was administered oral every day till the mice died. The rodents form both groups were weighed every 48 hours and were registered the day they died. The statistical evaluation from the data was realized for the anova test. It was observed the difference between the two groups with the Tukey test. The values with p<0.05, were consideration statistical significantly different.The Grow tumor was measure in grams and this one was smaller in treatment group as difference form the control group. The group treatments wash increment of the life time respect to the control group. In the present work, the use of etanolic extract of Prunella Vulgaris wash partiality inhibited of the grow tumor, and prolongation of the life time. 63 GENDER DIFFERENCES IN THE INDUCTION OF TYPE 2 DIABETES WITH A STREPTOZOTOCIN-NICOTINAMIDE MODEL. Alonso-González Sonia Areli, MárquezFlores Yazmín Karina, Martínez-Galero Elizdath, Meléndez-Camargo María Estela. Departamento de Farmacia, ENCB-IPN. México. Email [email protected] Introduction: the establishment of experimental models is crucial for understanding the pathogenesis and development of new diabetes treatments. Epidemiological data indicate that the disease is more prevalent in women; however experimental commonly used male rats for the diabetes type 2 (DM2) evaluation. On this basis, this study aims to determine the gender differences in DM2 induced with streptozotocin (ETZ) and nicotinamide (NA) model. Method: adult female (200 20 g body weight) and male Wistar rats (300 50 g body weight) were used. For each case a control and diabetic group were formed. DM2 was induced with ETZ (65 mg/kg; ip) and NA (120 mg/kg; ip) 15 minutes after ETZ administration. The water and food consumption were recorded daily in 4 rats samples of each group. Urinary and blood samples on days 21, 28, 35, 42 and 48 were obtained for glucose, protein and ALAT concentration determination. With these values, urinary flow, glucose clearance and diabetic rat percentage were calculated. Results: both cases DM2 rats with, showed a water and food intake increase as well as an urinary flow increase. In female rats, a longer hyperglycemic state was observed (even to 48 days) compared with male rats (even to 35 days). The higher diabetic rat percentage was 78.6% (28 days) and 46.7% (21 days), respectively. Conclusion: female rats presented for a longer time and a higher percentage of hyperglycemic state with DM2 EZT-NA model. SYNTHESIS OF THE RINVANIL AND ITS ANTIPROLIFERATIVE AND APOPTOTIC 1 PROPERTIES ON CERVICAL CANCER CELL LINES. Alvarado Sansininea Jesús Javier , 1 1 1 Luviano-Jardón Axel , Hernández Vázquez José Misael Vicente , López Muñoz Hugo , 2 1 1 1 Escobar Sánchez Ma. Luisa , Weiss-Steider Benny , Regla Ignacio , Sánchez-Sánchez Luis 1 [email protected] Facultad de Estudios Superiores Zaragoza, Universidad Nacional 2 Autónoma de México, 09230 México D.F., México. Departamento de Biología Celular, Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México, D. F., México. Cervical Cancer is the second major cause of death in women; actually there are few selective treatments to aboard the latest phases in the disease. The present drugs have several side effects and they have a little selectivity function, it generates the necessity to develop new selective compounds to the cancer treatment. It is known the Capsaicinoids and derivate have an antiproliferative effect in human cancer cell lines. Newly capsaicinoides analogues attempt to find new compounds with apoptotic, and antiproliferative activity, as a selective function against the cancer cells. In this work the apoptotic, antiproliferative, and cytotoxic activity of the Rinvanil an analogue of capsaicin was evaluated on cervical cancer cell lines HeLa, CaSk CaSki, and ViBo respectively. Rinvanil diminish the CasKi and HeLa percentage cells in G1 phase, and increases the subG1 cellular number. However the ViBo cells are not affected in the cellular cycle. The cytotoxic effect indicate that Rinvanil affect in 26.31%, 13.47%, and 7.89% in CaSki, ViBo, and HeLa respectively. An increased level of active Caspase-3 was observed with the Rinvanil treatment in all the cell lines, indicating a apoptotic property. Interesting Rinvanil does not have a cytotoxic effect, and eater does not affect to the proliferative potential in non tumoral cells fibroblastic and lymphocytic cells. These results show to the Rinvanil as a selective antitumor activity compound and therefore serve as a promising lead candidate for further optimization 64 SYNTHESIS OF THE CHOLESTANE GLYCOSIDE (25R)-3Β,16Β-DIACETOXY-22OXOCHOLEST-5-EN-26-YL Β-D-GLUCOPYRANOSIDE AND ITS ANTICANCER a PROPERTIES ON CERVICOUTERINE CELL LINES. Alvarado Sansininea Jesús Javier , a b a Torres Pineda Daniela Berenice , María A. Fernández-Herrera , Hugo López-Muñoz José a a c M. V. Hernández-Vázquez , Moisés López-Dávila , María Luisa. Escobar-Sánchez , B. d* b* a* Mario Pinto , Jesús Sandoval-Ramírez. and Luis Sánchez-Sánchez a [email protected] Facultad de Estudios Superiores Zaragoza, Universidad Nacional b Autónoma de México, 09230 México D.F., México. Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla. Ciudad Universitaria, 72570 Puebla, Pue., c México. Departamento de Biología Celular, Facultad de Ciencias, Universidad Nacional d Autónoma de México, Ciudad Universitaria, 04510 México, D. F., México. Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6. Certain saponins are bioactive compounds and have medical uses. It has been reported that saponins have properties such as anticancer, hypocholesterolemic, hypoglycemic and anti-oxidant activity. The diverse activity of saponins could be explained by its complexity of chemical natures. Structurally, saponin has a general backbone structure, a policyclic aglycone of either steroid or triterpenoid in nature. Diosgenin is a steroidal sapogenin with estrogenic and antiproliferative activity and induce apoptosis in several cell lines. In this work, the synthesis of the new cholestane glycoside (25R)-3β,16β-diacetoxy-22-oxocholest-5-en-26-yl β-D-glucopyranoside (26-OH-Di-Glu) starting from diosgenin is described and its anticancer properties on cervicouterine cell lines were tested. In order to evaluate its antitumor activity, we determined their effect on cell proliferation, cell cycle, and cell death. The cytotoxic effect of the compound on HeLa, CaSki, ViBo cell lines, and human lymphocytes was also evaluated; the results show a null effect on tumoral cells as on lymphocytes cells, implying that 26-OH-Di-Glu is not cytotoxic. The compound inhibits the growth of tumor cells with IC50= 20 µg/mL in HeLa and ViBo cells and 23 µg/mL in ViBo cells. The observation of apoptotic bodies as well as the increase in the expression of active caspase-3 along with the fragmentation of DNA, confirmed that 26-OH-Di-Glu induced apoptosis in tumor cells. Significantly, its antiproliferative activity on tumor cells did not affect the proliferative potential of peripheral blood lymphocytes. The compound shows selective antitumor activity and therefore serves as promising lead candidate for further optimization. NEUROPROTECTIVE EFFECT OF SIMVASTATIN IN AN EXCITOTOXIC MODEL 1,2 1 INDUCED BY QUINOLINIC ACID Anaya-Ramos Laura , Tristan-López Luis , Monroy2 1 3 1 Noyola Antonio , González-Esquivel Dinora , Pineda-Olvera Benjamin , Ríos Camilo , Pérez1 1 2 Severiano Francisca , Departamento de Neuroquímica INNN. Facultad de Farmacia 3 UAEM. Departamento de Neuroinmunologia. Recent evidence suggests that statins as simvastatin (SIM) have neuroprotective action in different neurodegenerative conditions as Huntington’s disease (HD). Even when their mechanism of protection have not been elucidated completely, it has been proposed that could be due to antioxidant properties related to an increase in the paraoxon-1 activity, making them a possible pharmacologic therapeutic option. Quinolinic acid (QUIN) is an endogenous agonist of N-methylD-aspartate (NMDA) receptors, widely used as an experimental model of the excitotoxicity related to HD. Four experimental groups of seven male Wistar rats were used (n=28, w=200-250g) according to the treatment administered intraperitoneally: SIM (5 mg/Kg) or DMSO during 7 days. After this treatment groups were separated into QUIN (240 nmoles/µl) or isotonic saline solution (ISS) by striatal administration: Group I, DMSO+SSI; group II, SIM+SSI; group III, DMSO+QUIN and group IV, SIM+QUIN. Animals body weight was recorded daily. After 6 days of QUIN-induced damage, circling behavior was done and striatal GABA levels were determined by HPLC. Results showed a decrease of 42% in ipsilateral turns in SIM group in comparison with the damage-control group and GABA level was preserved in relation to QUIN group (p<0.05). These preliminary results show a neuroprotective effect of SIM against neurotoxicity induced by QUIN, which will be complemented with other studies. 65 METALLODRUGS WITH ANTINEOPLASIC ACTIVITY OF BINUCLEAR HETEROLEPTIC a PT(II) AND PD(II) COMPLEXES. Gabriel A. Andreu-de-Riquer , Alejandro Urquietab a c Velázquez , María de los Ángeles Mendoza , Lena Ruiz-Azuara , Myrna L. Sabanerob a a López and Luis. A. García-de-la-Rosa . Chemistry Department, Division of Natural and Exact Sciences, University of Guanajuato, Pueblito de Rocha, 36040, Guanajuato, Gto. b Mexico. Biology Department, Division of Natural and Exact Sciences, University of c Guanajuato, Noria Alta s/n, 36000, Guanajuato, Gto, Mex, Inorganic and Nuclear Chemistry Department, Faculty of Chemistry, UNAM, Mexico City, 04510, Mexico. A series of platinum(II) and palladium(II) complexes with hexadentate TPXN type ligands 195 (TPEN, TPTN and TPHN), were synthesized and characterized. The Pt NMR spectrum indicates that a single type of platinum atom is present. Redox properties of these compounds have been investigated by cyclic voltammetry. The increase of the length of the spacer arm in the ligand presents a favorable effect on the platinum complexes, diminishing their activation energy. Among all the studied complexes [Pd 2(II)TPHNCl2]Cl2 presented the highest antineoplasic activity in transformed lung cells, similar to the one shown by cisplatinum, i.e. damage to microtubules from cytoskeleton and nuclei, profile DNA genomic shown light changes. Furthermore, growth alterations, profile proteins changes; possibility the alteration of DNA originated by palladium complex it is reflects in quantitative decrease of proteins. The results shown that palladium (II) complex, cause alterations at different cellular levels, we can assume that palladium (II) complex, might have different biological mechanism of action. It becomes evident that the most careful and guided ligands selection is fundamental to obtain metallodrugs with anticancer property. BIOMARKERS: EXPRESSION OF SPHINGOMYELINASE AND CERAMIDASE IN SERUM AND KIDNEY OF DIABETIC RATS. Abraham Arellano, Martha Franco, Rocío BautistaPérez. Department of Nephrology, Instituto Nacional de Cardiologia ―Ignacio Chavez‖. [email protected] Introduction: It has been suggest that enzymes involved in ceramide generation (neutral sphingomyelinase [N-SMase], acid sphingomyelinase [A-SMase], and serine-palmitoyltransferase [SPT]) and ceramide hydrolysis (ceramidase) can to contribute to the progression of microvascular disease in diabetes. Therefore, these enzymes can be used as biomarker. A biomarker is a biologic characteristic that is measured and evaluated objectively as an indicator of normal biologic processes, pathogenic processes, or pharmacologic response to therapeutic intervention. Typically these are immunohistochemical stains but, more recently, mRNA or protein. In this study we evaluated the expression of N-SMase and ceramidase in serum and kidney of diabetic rats at protein levels. Methods: Experiments were performed in male Wistar rats weighing 300-350 g. The rats were divided into two groups: control and diabetic rats (n=10 each). We evaluated the expression of N-SMase and ceramidase in serum and kidney of diabetic rats at protein levels by Western blot. Results: Four weeks after treatment with STZ, the body weights of the diabetic rats were significantly lower than those of the control rats (263 ± 8 g vs. 363 ± 10 g), and the diabetic rats were hyperglycemic (23.77 ± 0.5 mmol/L vs. 4.7 ± 0.4 mmol/L). We observed that only increased expression of the ceramidase at protein levels in the serum of diabetic rats compared with those of controls (2019 ± 65.41 vs 959.2 ± 28.28 arbitrary units). Conclusion: Expression of ceramidase in serum can be used as biomarker in diabetes. Acknowledgment: This project was supported by a Mexican Council of Science and Technology (CONACYT) Research Grant (No. 60979) awarded to R.B.-P. 66 INOSINE EFFECT ON INSULIN SIGNALING IN C9 HEPATIC CELLS; MOLECULAR MECHANISMS. Arellano-Plancarte A., Villalobos-Molina R. Unidad de Investigación en Biomedicina, Fes-Iztacala UNAM Inosine is a purine nucleoside formed from the breakdown of adenosine, is metabolized to xantine and uric acid by xanthine dehydrogenase. Although inosine was widely believe to be inert, in recent years has been demonstrated that inosine inhibits the release of proinflammatory cytokines and chemokines, and that exerts anti-inflammatory process, also several reports suggest a benefit effect of inosine on blood glucose levels and the inosine treatment appears to protect against the development of type 1 diabetes in a mouse model. However despite the beneficial effect of inosine on glucose levels that has been proposed, at least one report suggests that when inosine is released after hypoxia activates hepatic glucose liberation having a hyperglycemic effect. For this time the effect of inosine on glucose levels is controversial and the molecular mechanisms involved are still unknown. The purpose of this work is to investigate in a hepatic cell line the effect of inosine on key proteins and events of the insulin signaling. The results showed that inosine treatment inhibits insulininduced glycogen-synthase phosphorylation on serine 641/645 and Akt 1/2/3 thr 308 phosphorylation, suggesting that inosine treatment have a negative regulatory role on insulin signaling, however interestingly we also showed that inosine treatment potentiates insulininduced Akt 1/2/3 ser 473 phosphorylation suggesting a dual effect on Akt. How inosine induces its effect and what proteins are involved are the questions that we are now trying to resolve. DISCRIMINATIVE PROPERTIES OF AMPHETAMINE AND MODAFINIL. Argüelles1 1,2 1 1 Hernández R , Mendoza-Meléndez M.A.G. , Pinzón-Estrada E , López-Cabrera M . 1 2 Departament of Pharmacology, School of Medicine. Departament of Psychophysiology, Faculty of Psychology. National Autonomous University of Mexico , México DF, 04510, México ([email protected]) Amphetamine (AMPH) is a psychostimulant drug that produces release of dopamine (DA) and norepinephrine (NE) in the presynaptic terminal and blockades the reuptake from the synapse. The stimulus control exert by AMPH is mediated by D2. Modafinil interact with multiple molecular targets in the brain (α-adrenergic receptor, 5-HT, GABA, glutamate, histamine), including DAT proteins. Substantial evidence indicates that modafinil exerts its effects via presynaptic dopaminergic mechanisms, inhibits DA transporter (DAT).The purpose of the present study was to determine if AMPH was able to produce a dose dependent stimulus gradient and if Modafinil substitute the discriminative cue produced by AMPH. Subjects were 20 male Wistar rats, trained to discriminate AMPH (3 mg/kg, i.p.) from vehicle in a two operant task; each lever was correlated with a fixed ratio (FR10) schedule of reinforcement. Results: Discrimination test and substitution test data are expressed as the mean percentage of response on the drug-appropriate lever in each period with different doses of AMPH and modafinil and were analyzed with one-way ANOVA. We found that AMPH was able to exert control over lever selection in the drug discrimination task by producing a dose dependent stimulus gradient. 67 EVALUATION OF ANTITUMORAL ACTIVITY OF SOME KALANCHOE SP. EXTRACTS IN VARIOUS CANCER CELL LINES AND THEIR GENOTOXICITY. Arias González Iván, Licona Flores Emmanuel A., Burgueño Tapia Eleuterio, Arriaga Alba Myriam and OrdazPichardo Cynthia. Escuela Nacional de Medicina y Homeopatía del IPN, México. Cancer is a group of diseases characterized by abnormal and uncontrolled growth of cells. Is currently the most common cause of death in the population, by far, lung is the most common fatal cancer in men (30%), followed by prostate (9%), and colon-rectum (9%). In women, lung (26%), breast (15%), and colon-rectum (9%) are the leading sites of cancer death. Ethno-pharmacology has become a promising strategy for treatment human cancer. In fact traditional medicine employs plants and herbs to stop the development of cancer. Furthermore, these plants have one of the main sources of active drugs for new cancer chemoprevention. Kalanchoe sp. (family Crassulaceae) is widely employed in folk medicine in Mexico for treatment of wounds, burns, and diseases related to cell damage, particularly cancer.In this study, we investigated the cytotoxic effect of ethanolic, ethyl-acetate and hexane extracts of stems and leaves of Kalanchoe pinnata, Kalanchoe gastonis-bonnieri and Kalanchoe flammea by MTT and CV dying assay in various cancer cell lines. As many natural occurring compounds are genotoxic, we evaluate the mutagenic properties with or without CYP450 metabolic activation, using a preincubation procedure of the Salmonella assay (Ames test) with strains TA98, TA100 and TA102. In dose dependent manner ethanol and ethyl-acetate extracts decrement the cell viability against lung (A549), colon (HT29), prostate (PC3) and were not mutagenic on the Ames test. Hexane extracts was not cytotoxic against these cell lines and were mutagenic on strains TA98 and TA100. In summary our data suggest that ethyl acetate extract of Kalanchoe flammea is a potential candidate to realize further studies about its phytochemical components and their mechanism of action in cancer cells. CRATAEGUS OXYACANTHA PREVENTS OXIDATIVE DAMAGE AND UNCLOUPLING OF GAP JUNCTION INTERCELLULAR COMMUNICATION IN EXPERIMENTAL LIVER CIRRHOSIS INDUCED BY ETHANOL. Lorena Ávila-Carrasco*, José Luis Alvarado-Acosta, Rosalinda Gutiérrez-Hernández and Patricia Yahuaca-Mendoza. Programa de Doctorado en Farmacología, U.A. de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, México. E-mail: [email protected] Alcoholic cirrhosis usually presents oxidative stress. Due to the need for new therapeutic strategies in alcoholic cirrhosis, we studied the effect of Crataegus oxyacantha whose antioxidant action has been described. To determine the involvement of C. oxyacantha it was induced a model of alcoholic cirrhosis by 12 weeks in Wistar rats, which were co-administered with an extract of C. oxyacantha at a dose of 100 mg/kg. The oxidation degree and liver damage were determined by hepatic lipid peroxidation (LPox) and erythrocyte plasma membrane stability (EPME), as well as serum activities of gamma-glutamyltranspeptidase (-GTP) and alanine aminotransferase (ALT), total bilirubin, liver glycogen and histological changes. Furthermore, Lucifer yellow transfer in liver parenchyma was measured to assess the GJIC. In alcoholic cirrhosis, LPox increased 3.2 times over the control, while EPME decreased to 50%. These results confirm a noticeable oxidative stress, related to metabolic and enzymatic damage, since -GTP and ALT, increased by 43% and 164% respectively; bilirubin increased by 412%, while the basal glycogen storage was depleted up to 17%. GJIC decreased in alcoholic cirrhosis, evidenced by less transfer of Lucifer yellow, which was prevented by administering C. oxyacantha, which also prevented the alterations on systemic and hepatic oxidative damage, reducing the LPox, and partially avoiding loss of EPME while the GJIC was recovered. These preliminary results support the potential usefulness of Crataegus oxyacantha phytotherapy to alleviate and prevent some alterations during the experimental alcoholic cirrhosis. Project funded by SEPPIFOP 2002-33-04 and Fondo Sectorial SEP-CONACYT, Ciencia Básica, CB-20080105986* Number 15607 CONACYT. 68 EFFECTS OF 17Β-AMINOESTROGENS ON MCF-7 CELLS PROLIFERATION. María Estela Ávila, Martha Medina-Jiménez and Cristina Lemini*. Departamento de Farmacología Facultad de Medicina Universidad Nacional Autónoma de México. Av. Universidad No. 3000, CP 04510, Delegación Coyoacán, México, D.F., México. *[email protected] 17β-aminoestrogens (AEs) produce anticoagulant effects that contrast with those procoagulant of 17β-estradiol (E2) in rodents. AEs decrease LH, increase uterine weight and induce lordosis behavior of the female rat, activating transcription through the estrogen receptors (ERα, ERβ). The aim of this work was to explore the AEs capabilility to induce proliferation of MCF-7 human breast cancer cells which is estrogen dependent. Viability was estimated in metabolically active cells by the MTT assay. 2500 cells per well in 96 well plate were left to atach for 24 h and treated during six consecutive days with different -12 -11 -10 -9 -8 -7 -6 concentrations (10M , 10M , 10M , 10M , 10M , 10M and 10M ) of the AEs: prolame, butolame, pentolame, E2 and as control, cells without treatment. To test the receptor mediation of the cells proliferation rate, the AEs were coincubated with 1 mol/L of the antiestrogen tamoxifen. The AEs produced biphasic responses on the MCF-7 cells proliferation. -12 -9 From 10M to 10M induced a linear proliferative effect. The AEs proliferative effect on MCF-7 cells related to the control was: E2=3.33; prolame=3.00; butolame=3.39; and pentolame 2.72. Their relative proliferative effect to E2 (100%) was: 86%; 103% and 77%. Their relative potency to E2 (100) was: 90, 96, and 95 respectively. Tamoxifen inhibited the AEs proliferative responses in a similar way to E2 suggesting the participation of the ER -8 -6 receptors in their proliferative action. From 10M the response decreased and at 10M AEs induced inhibition of MCF-7 cells proliferation. This response was not inhibited by tamoxifen indicating other mechanism involved in their antiproliferative response. EVALUATION OF 3-MERCAPTOPROPIONIC ACID INDUCED SEIZURES IN WISTARKYOTO AND WISTAR RATS. Bañuelos-Cabrera I., Orozco-Sánchez S. Rocha L.L., Center for Research and Advanced Studies of National Polytechnic Institute. Medical Research Unit in Neurological Diseases. Specialty Hospital. National Medical Center, Century XXI, IMSS Patients with depression show greater susceptibility to suffer epilepsy, but so far there are no animal models to study this comorbidity. The present study was carried out to determine the seizure susceptibility of Wistar Kyoto rats that normally show depressive-like behaviors. Seizure activity was induced by daily administration of 3-mercaptopropionic acid (3-MP, 37.5 mg / kg, i.p.) for 10 days. The results obtained were compared with those from Wistar rats. In WKY rats, the seizures induced by the repetitive 3-MP acid were as follows: 82% myoclonus, 70% clonus, 49% tonic seizures. In contrast, Wistar rats presented 76% of myoclunus, 49% of clonus and 35% of tonic seizures. The statistical analysis revealed that WK animals presented high incidence of clonic seizures. Therefore, we conclude that the WKY strain is most susceptible to suffer seizures than Wistar strain. (Supported by CONACyT grant 98386 and scholarship 333114/232762). 69 PREVALENCE OF CHRONIC DISEASES AND POLYPHARMACY IN ELDERLY PATIENTS ATTENDING A DENTAL FIRST LEVEL OF ATTENTION. Barrueco Noriega 1 2 3 1 Guadalupe Sara , Suarez Guerrero Ivonne , Rodríguez García Rosalía . UMF N. 38 IMSS, 2 3 Universidad Autonóma Metropolitana Xochimilco, Hospital Regional ―Lic. Adolfo López Mateos‖ ISSSTE. The presence of aged patients in the dental office is increasingly common, however it is important to note that this population suffers from multiple chronic diseases and use of several drugs at once. To the extent that the dentist knows the physiological changes and comorbidities of these patients carry out a more timely and safe practice. To determine the prevalence of chronic diseases and polypharmacy in older patients attending dental clinic in a primary care level. We did an observational descriptive crosssectional, 99 patients 60 years old and over attending dental clinic in 2010, in an IMSS family medicine. Last reviewed the medical notes of each patient in the information system of family medicine, were asked how many patients consumed daily medications, informed consent. Variables: gender, age, number of chronic diseases and number of drugs that consumed time. 54.5% of patients were female with an average age of 71.2 years. The average was 3.4 chronic diseases, polypharmacy was present in 73.7%, with an average of 5.7 drugs ingested daily. According to age and number of chronic diseases were found statistically significant results p = 0.004. As observed comorbidity and polypharmacy favors older physiological capacities of elderly are decreased. In dental practice these aspects are rarely taken into account as the frequent use of AINES and antibiotics in this population as vulnerable can lead us to the presence of any adverse reactions. CERAMIDE-PHOSPHOLIPASE A2 INDUCED VASOCONSTRICTION IN THE ISOLATED 1 1 1 PERFUSED RAT KIDNEYS Rocio Bautista-Pérez, Abraham Arellano, Martha Franco, 2 1 Bruno Escalante. Department of Nephrology, Instituto Nacional de Cardiologia ―Ignacio 2 Chavez‖. CINVESTAV-Monterrey. [email protected] Background/Aims: Sphingolipids can be hydrolyzed by sphingomyelinase (SMase) to generate ceramide. Ceramide can interact directly with cytosolic phospholipase A2 (cPLA2) and regulates arachidonic acid (AA) metabolism in many cell types. Thus, this study was performed to investigate whether there is interaction between SMase and cPLA 2 signal transduction pathways and how this might contribute to the renal vascular response. Methods: To evaluate the renal vascular response to exogenous SMase, experiments were performed on isolated perfused rat kidneys in the presence and absence of inhibitors of arachidonic acid metabolism. Results: Exogenous SMase (0.4 units) constricted the vasculature in the isolated perfused rat kidney (30.38±2.2 mmHg). Renal vasoconstriction was diminished by arachidonyl trifluoromethyl ketone an inhibitor of cPLA2, 5,8,11,14eicosatetraynoic acid an inhibitor of all AA pathway, indomethacin an inhibitor of cyclooxygenase (COX), furegrelate an thomboxane A2 (TXA2) -synthase inhibitor, SQ29548 an TXA2-receptor antagonist (12.55±0.75, 13.46±0.5, 8.2±1.6, 9.5±0.5, 11.4±0.97 mmHg respectively). In addition, the bolus injection of SMase also was associated with an increase in the release of thomboxane B2 (TXB2), the TXA2 metabolite; the TXB2 production was inhibited by indomethacin and furegrelate (750±100, 350±75, 250±75 pg/ml respectively). Conclusion: Our results show that ceramide released by SMase activate cPLA2 to release AA, and hence the AA can be metabolized by COX pathway to form TXA2 in isolated perfused rat kidney, this signaling pathway represents a novel signal transduction mechanism for renal vasoconstriction. Acknowledgment: This project was supported by a Mexican Council of Science and Technology (CONACYT) Research Grant (No. 60979) awarded to R.B.-P. 70 ANTIALLODYNIC EFFECT OF MELOXICAM AND PROGLUMIDE IN DIABETIC 1,3 2 1 NEUROPATHY. Bermúdez-Ocaña DY , Suarez-Méndez S , Tovilla-Zárate CA , Ramos2 1 4 5 2 Domínguez R , Ramón-Frías T , Díaz-Zagoya JC , Granados-Soto V , Juárez-Rojo I . 1 2 3 UJAT-DAMC, Comalcalco, Tabasco. UJAT-DACS, Villahermosa, Tabasco. Hospital de 4 Alta Especialidad Dr. Gustavo A. Rovirosa Pérez, Villahermosa, Tabasco. UNAM, D.F., 5 México. CINVESTAV-Coapa, D.F., México. Diabetic neuropathy is a common complication of diabetes that represents a major world health problem. This type of pain is often characterized by stimulus-independent persistent pain or abnormal sensory perception of pain, such as allodynia and hyperalgesia. Moreover, conventional analgesics that relieve acute pain cannot exert sufficient effects on neuropathic pain associated with diabetes and no potentially effective drug for treatment of this pain is currently available. The aim of this work was to evaluate the effect of meloxicam and proglumide combination in diabetic neuropathy. The experiments were performance using male Wistar rats on weight 280-320 g. Rats were injected with streptozotocin (60 mg/kg i.p.), three days later, hyperglycaemia was confirmed using an Accu-Chek blood glucose monitoring system. Four weeks after diabetes streptozotocin injection, glycaemia was again determined and only animals with a final blood glucose level ≥300 mg/dl were included in the study. The paw withdrawal threshold was determined by the up-down method of Dixon and Chaplan et al. Allodynia was considered to be present when paw withdrawal thresholds were 4 g. Streptozotocin injection caused hyperglycemia. Four weeks after diabetes induction Meloxicam and proglumide was evaluated in diabetic rats. Meloxicam (10, 30 mg/kg, i.p.) significantly reduced allodynia in diabetic animals, but not vehicle. In addition, proglumide (40, 80, 160 mg/kg, i.p.) produced increased the withdrawal threshold. Moreover, meloxicam and proglumide combination diminished allodynia in diabetic rats. Results suggest the participation of COX and CCK pathway in diabetic neuropathy. Supported by PFICA, grant 2009-C05-55. ROLE OF THE 5-HT6 RECEPTOR IN THE STRESS RESPONSE AND ITS COGNITIVE 1 2 2 2 IMPLICATIONS. Briones-Aranda A. , Ossio R. , Quirarte G.L. y Prado-Alcalá R.A. ; 1 Facultad de Medicina Humana, Universidad Autónoma de Chiapas, 2 Dpto de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, UNAM, Campus Juriquilla. The 5-Hydroxytryptamine6 (5-HT6) receptor has been implicated in the process of memory consolidation and associated with some aspects of the stress response regulation The aim of this study was to investigate, by the use of pharmacological tools, the implication of the 5HT6 receptor in the formation (or consolidation) of memory and how it can be affected by a prior exposure to acute stress. The stressor employed was a modified version of the forced swimming test (FS) 24 hours before training. The cognitive test used was a two trial novel object recognition task (NORT). One-hundred and twenty male Wistar rats, weighing 250 to 300 grams, were divided into 12 groups. The first four groups were treated with saline or the 5-HT6 receptor antagonist SB-271046 (5 mg/kg), which were administered i.p. immediately after training to animals with or without previous FS. The other 8 groups followed a similar pharmacological regime, with the antagonist RO-046790 (10mg/kg; i.p.), and the agonists E6801 and E-6837 (5 mg/kg; i.p.). The animals were trained and evaluated 24 hours later. The results show a decrease in the discrimination ratio of the previously stressed animals, an effect directly related to affected memory consolidation. This effect was reversed by the administration of both agonists, but by neither of the antagonists of the 5-HT6 receptor. It is therefore likely that the effect of stress on cognitive processes is related to possible changes in the number and functioning of 5-HT6 receptors. However, further research is necessary to explore this hypothesis. The authors are grateful to the ESTEVE company for donating the drugs and the technical assistance of Ángel Mendéz, Martin García, Norma Serafin, Omar González and Leonor Casanova. Supported by CONACyT 130524 and PAPIIT-UNAM. 71 EFFECT OF SIBUTRAMINE AND L-CARNITINE ON THE LEVELS OF 5-HIAA AND GSH IN THE BRAIN REGIONS OF RAT WITH LOW AND NORMAL PROTEIN DIETS. David 1 2 2 Calderón Guzmán , Ernestina Hernández García , Francisca Trujillo Jiménez , Hugo 2 1 1 Juárez Olguín , Gerardo Barragán Mejía , Francisco Javier Pierdant Rioja , Eduardo Tena 3 3 1 Betancourt , Jaime Herrera Perez . Laboratorio de Neuroquímica, Instituto Nacional de 2 3 Pediatria (INP) Laboratorio de Farmacología, INP. Cirugía Experimental y Bioterio, Centro Médico Nacional Siglo XXI. Weight reducing drugs like sibutramine and L-carnitine directly act on central nervious system (CNS). However, the effect of these drugs on serotonergic system of animals on hypoproteic diet is still unknown. Based on the above, the objective of the present study is to determine the effect of sibutramine and L-carnitine on 5-HIAA and GSH levels in brain regions of rat fed with low and normal protein diets. Young female Sprague Dawley rats on normal (23% protein) and hypoprotein (7% protein) diets were used. The animals were distributed by chance in groups of 4 per diet, and were treated for 10 days as follows: group 1, saline solution NaCl 0.9%; group 2, sibutramine (10mg/kg), group 3, L-carnitine (500mg/kg); grupo 4, sibutramine (10mg/kg) + L-carnitine (500mg/kg). All treatments were administered intraperitoneally. The animals were sacrificed by decapitation at the end of treatment, and their cerebrum, cortex, hemisphere, cerebellum, and medulla oblongata were extracted to determine the levels of glucose, glutathione (GSH), lipid perioxidation (Tbars), and 5-hydroxilindol acetic acid (5-HIAA). The weight of animals with low protein diet was found to be significantly lower (p<0.05) in comparison with the groups of animals on normal diet. Based on the results, it is suggested that sibutramine and L-carnitine induce biphasic antioxidant effect, and alter serotonergic metabolism in the brain regions of female rats under different nutritional conditions. EFFECT OF SIBUTRAMINE ON 5-HIAA LEVELS AND SELECT OXIDATIVE BIOMARKERS ON FEMALE RAT BRAIN REGIONS IN PRESENCE OF ZINC. David 1 2 1 Calderón Guzmán , Ernestina Hernández García , Gerardo Barragán Mejía , Hugo Juárez 2,3 2 2 1 Olguín , Erick Buendía Soto , Francisca Trujillo Jiménez , Daniel Santamaria del Angel , 1 1 Liliana Carmona Aparicio Laboratorio de Neuroquímica, Instituto Nacional de Pediatría 2 3 (INP), México. Laboratorio de Farmacología, INP. Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México. Some drugs that are clinically used in weight control, like sibutramine, act on the serotonergic metabolism, but its relation with zinc and free radical (FR) production in the CNS is still unknown. Aim: To evaluate the effect of sibutramine and zinc on FR production. Methods: Female Wistar rats about 250g weight were used; animals received sibutramine (10mg/kg and zinc 400µg/kg each 36 hours) intraperitoneally during 15 days. At the end of the study, the rats were sacrificed and its brains used to measure lipid peroxidation (TBARS), reduced glutathione (GSH), hydrogen peroxide (H2O2), calcium and 5-hydroxyindole acetic acid (5HIAA) levels, by means of validated methods. Results: The corporal weight and food consume were decreased in sibutramine plus zinc group. TBARS decreased in cortex, hemispheres and medulla oblongata, likeness, GSH decreased in cortex, hemispheres and cerebellum by effect related to sibutramine group. Zinc given alone and combined with sibutramine decreased H2O2 concentration in the cortex, hemispheres and cerebellum, but increased calcium and 5-HIAA concentration in all brain regions. Our results suggest that sibutramine and zinc produce an antioxidant effect on different brain regions and both may be used to potential the control of food intake and lowering body weight in the clinical practice. 72 ADMINISTRATION OF 25-35 OF AMYLOID BETA FRACTION OVER EXPRESSION OF 1 HEAT SHOCK PROTEINS AND SITES OF GLYCOSYLATION IN CELLS C6. Calvillo M. , 2 3 3 Espinosa B. Zenteno E. , Guevara J. 1.- Experimental laboratory. of Neurodegenerative Disease, National Institute of Neurology and Neurosurgery. 2.- Laboratory of Biochemistry, National Institute of Respiratory Disease 3.- Department of Biochemistry, Medicine Faculty, UNAM. Heat shock proteins (Hsps) are expressed in response to several stress forms. Since the protein synthesis is increased, there is interest to investigate the Hsps role in pathology of Alzheimer disease (AD). It is known that Hsps interact directly with betasome one Hsps has been attributed lectinic activity i.e., they are capable of recognizing glicoconjugates residues. Therefore, the objective of this work was to observed the effect of the 25-35 fraction beta-35, the cells were processed to immunocytochemistry technique with antibodies for Hsp27, 60, 70, 90 and 105, and seven lectins (ALL, ConA, MAA, MRL, SNA, PNA and WGA). The images were acquired with software IM100 of Leica microscopy. The results show that inmunoreactivity levels in HsPs are increasing to respect to time of incubation when compared to control gruop.Iinmunoreactivity level of ALL, MAA and MRL was a little bit. Inmunoreactivity level of Con A, PNA and WGA was very abundant; SAN had shortly increased th -35 during incubation didn’t change respect to control group. It is known that C6 cells express high activity of synthesis and secretion of glycosaminoglycans. Proliferative and adhesive properties of the C6 are dependent on the expression of surface glycoproteins. It was concluded that the stress -35 modifies Hsps inmunoreactivity and sites whose recognized lectins are modified. Biochemical determinations will be made to learn about the relationship between these proteins in vitro study. ANTIOXIDANT ACTIVITY OF TLANCHALAGUA (ERYTHRAEA TETRAMERA SCHIEDE) 1 2 1 1 Camacho Luis Abelardo, Esteban Méndez Maricela, Jesus María Araujo Contreras, Ávila 3 1 Rodríguez Humberto, Vértiz Hernández Ángel Centro de investigación en Alimentos y 3 2 Nutrición, Facultad de Medicina, Facultad de Ciencias Químicas- UJED, CIIDIR-IPN, Unidad Durango Plants must protect themselves from oxidation induced by UV radiation exposure in the outdoor environment where they grow. These protective mechanisms have evolved over many years and have provided interesting chemicals that can be learned and incorporate in cosmeceuticals products. Antioxidants are compounds that can eliminate ROS and protect the body from free radicals. It has aroused great interest in free radicals and its relation to cell aging. This increased oxidative stress at the cellular level resulting in pathophysiological processes such as cancer, cardiovascular disease, neurodegenerative (Alzheimer, Parkinson) and cataracts. Therefore, it is vitally important to find molecules that are able to minimize or prevent damage caused by free radicals. To determine the antioxidant capacity of tlanchalagua (Erythraea tetramera Schiede) Plant extracts was obtained by reflux with different solvents for 6 hrs, then concentrated under reduced pressure yielding about 10 ml. Different concentrations were prepared extracts and tested for antioxidant activity with ABTS (2.2 '-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid). We evaluated the ability to capture free radicals by the ABTS assay of each extract. There is a higher antioxidant capacity in the ethanol extract (91.48%), followed by ethyl acetate extract (82%), as for the other two extracts were not able to determine the activity because the extract is not completely solubilized in the system. Phytochemical screening of methanolic extract showed flavonoids principally. Conclusions: Ethanol extract was the most powerful, with 91.48% of inhibition, phytochemical screening showed flavonoids, this compounds are responsible of antioxidant activity of the extract, methanol and water extracts was not possible to determine the percentage of antioxidant capacity due to the turbidity of the sample, making it necessary to use other technique is effective. 73 NEONATAL MONOSODIUM GLUTAMATE ADMINISTRATION DECREASE AMPHETAMINE INDUCED LOCOMOTOR ACTIVITY SUSCEPTIBILITY EFFECTS IN ADULT MICE. Campos-Sepúlveda AE, Martínez-Enríquez ME, López-Cabrera M, Saldívar-González JA. Departamento de Farmacología, Facultad de Medicina, UNAM; México, D.F., 04510. Neonatal administration of monosodium glutamate (MSG) to mice causes neurotoxicity of the Central Nervous System (CNS) resulting in endocrine, metabolic and behavioral abnormalities. On the other hand the amphetamine is a potent stimulant drug on CNS because it induced catecholamine released. The aim of the present study was study the effect of neonatal treatment (male mice of the CFW strain) with MSG (2 mg/g sc on first and nd th th th 2 days after birth, followed by 4 mg/g on days 3 , 4 and 5 ) on the amphetamine (2.5 to 15 mg/kg ip) induced locomotor activity (LA), six months later MSG treatment. The control group was vehicle-treated only (saline injections). The LA was registered in a electronic system (Biological Research Apparatus, Activity Cage, UGO BASILE, Italy), for 60 min. The MSG treatment significantly (p< 0.05) decrease the susceptibility to the acutely administered amphetamina, a dose-dependent form, when compared either to the control group. The decreased susceptibility to the stimulant effects of amphetamine may occur as a consequence of changes in neural excitability, down regulation of dopamine-receptors, synthesis inhibition of catecholamines, or might be related to pharmacokinetics modifications, induced by neonatal treatment with MSG. EFFECT OF ISOPROTERENOL ON SYSTOLIC PRESSURE, HEART RATE AND HYPERTROPHY OF YOUNG AND OLD MICE PREVIOUSLY EXERCISED. Cano-Martínez 1* 2 1 1 Agustina , Flores-Chávez Pedro , Vargas-González Alvaro , y Nieto-Lima Betzabé . 1 2 Departamento de Fisiología y Departamento de Instrumentación Electrónica del Instituto Nacional de Cardiología ―Ignacio Chávez‖ México, D.F. México. ([email protected]). Homoeostasis is a dynamic equilibrium process adjustable to the age of organisms. When the cardiovascular system is disrupted, this is mismatched. Which could be partially or totally attenuated, depending on age and life style. It is proposed that exercise could reduce cardiovascular risk. The aim of the present work was to study the effect of treadmill training on systolic pressure (SP), heart rate (HR) and ventricular hypertrophy (VH) in young and old male mice with heart injury induced by isoproterenol (ISO). Four groups of each age were considered (n=6): sedentary/SS (saline solution), sedentary/ISO (7 daily ISO administrations, 5µg/g/d, s.c), exercised/SS (1h/day, 5days/wk, 5wk), exercised/ISO. ISO was administered 24h after last exercise session. SP and HR were measured weekly by the tail-cuff method. Ventricular weight/body weight ratio was calculated as criteria of ventricular hypertrophy. Young sedentary showed higher variation ranges on SP (10.3±1%) and HR (23.5±2%) compared to young exercised. ISO treatment decreased SP (18.96±1%) and HR (5.56±1%) in sedentary young. Old sedentary and exercised showed no significant differences on the variation ranges on SP nor HR. ISO decreased SP (16.25±1%) in sedentary old and HR (16.03±1%) in exercised old. Hypertrophy was detected in exercised/SS (10.1±1 and 10.5+1%), sedentary/ISO (15.7±1% and 22.3+2%) and exercised/ISO (19.3±2 and 7+2%) young and old respectively. Our results suggest that exercise had an stabilizer effect on HR and/or SP depending on the age, since this was observed in young but not in adult mice (HR), while SP was stabilized in both. Moreover, this suggest that arterial pressure stabilization by exercise could protect from adverse effects of a heart injury independently of the age. While the hypertrophy caused by heart injury could be accentuated in exercised young and attenuated in exercised old organisms. The effects of training and heart injury on cardiovascular system are age differentially adjusted. 74 PHARMACOEPIDEMIOLOGY OF PSYCHOACTIVE MEDICATION IN ADULT PATIENTS 1,3 IN THE PSYCHIATRIC DEPARTMENT OF DURANGO GENERAL HOSPITAL. Edgar 1 1 2 3 Cano-Torres, Ismael Lares- Asseff, Martha Sosa-Macías, Carlos Salas, Alberto Allegre1 1 4 1 1 Alonso, Carlos Galaviz-Hernández , Alexis Lares López, Verónica Loera C. Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional, CIIDIR-IPN Unidad 2 Durango, México. Departamento de Psiquiatría y Salud Mental, Hospital General de 3 Durango, México. Hospital San José y Escuela de Medicina del Instituto Tecnológico de 4 Monterrey, México. Universidad Tec-Milenio Durango, México. Background: Psychiatric diseases have become a public health problem owing to their increased prevalence. An option for their treatment is psychoactive medications, which are associated with multiple adverse effects. The purpose of this study was to determine the pharmacoepidemiology of psychoactive medication and the prevalence of psychiatric disease in adult patients seen at the Psychiatry Department at Durango General Hospital. Methods: Clinical histories of the patients were reviewed for patients over 18 years of age that were seen at the outpatient clinic of the Psychiatry Department at Durango General Hospital that required psychoactive medication. The study was conducted between January 2009 and February 2010. Results: The most commonly diagnosed conditions were the neurotic disorders, stress related disorders, and somatization disorders (42.9%), with the most common sub-classification being major depression with anxiety (26.3%). Seventy six percent of patients received more than one medication for their treatment. The most commonly prescribed medications were the selective serotonin reuptake inhibitors, with Fluoxetine being the most prescribed medication (42.2%). Anxiolytics were the second most prescribed group, with Clonazepam being the most prescribed medication within this group (67.8% of patients).Conclusions: Contrasting with the clinical practice guidelines, in which single drug therapy is recommended for most of the psychiatric diseases, only 23.24% of the patients received single drug therapy. The age group with most prescriptions was between 30 and 59 years of age. EFFECTS OF ANTIHYPERTENSIVE COMPOUNDS ON GLUCOSE UPTAKE OF ISOLATED CARDIOMYOCYTES FROM HYPERTENSIVE RATS ON A HIGH SODIUM 1 2 2 2 2 1 DIET. R. Carbó , N. Torres , V.Leguízamo R. González Y L. Martínez . Departamento 2 de Biomedicina Cardiovascular, Instituto Nacional de Cardiología ―Ignacio Chávez‖ and Laboratorio de Química del Miocardio, Facultad de Estudios Superiores-Cuautitlán, UNAM. México D.F. MÉXICO Hypertension is a common condition that may affect most people who live into old age. Uncontrolled high blood pressure increases the risk of heart disease, stroke, and kidney disease; it can also unnoticeably damage the heart, vessels, brain, and kidneys if not treated. Some medicaments can control it. Diuretics, beta-blockers, ACE inhibitors and calcium channel blockers. But they have side effects. In the laboratory of Dr. Martínez they developed new compound synthesized from Changrolin and prove to have very good antihypertensive results. Two of these compounds (one with morpholinic structure and the other with tiomorpholinic structure) were used on glucose uptake of cardiomyocytes from hypertensive rats to characterize its heart protection properties. Sodium, a major component of salt, can raise blood pressure by causing the body to retain fluid, which leads to a greater burden on the heart. Increasing glucose uptake is a way of protecting the heart from hypoxic events and it is promoted by the glucose transporters (Gluts). We raised the blood pressure in these animals by administrating a high salt diet and observe that hypertension does not permit the metabolic switch that would protect the cardiac cells during hypoxia. These compounds have successfully lowered the blood pressure and improved the metabolic state of cardiomyocytes from hypertensive animals as well as regulating the function of the glucose transporters. 75 ANTIOXIDANT ACTIVITY OF TOPIRAMATE: AN ANTIEPILEPTIC AGENT Cárdenas1 1 1 1 1 Rodríguez N *, Coballase-Urrutia E ,Huerta-Gertrudis B , García-Cruz M.E Laboratorio de Neuroquímica, Instituto Nacional de Pediatría, México.C.P. 04530 [email protected] Topiramate (TPM), a sulfate-substituted monosaccharide, is a novel compound that has a broad spectrum of antiepileptic activity in experimental and clinic studies. The mechanisms that likely account for the anticonvulsant activity of TPM include a negative modulatory effect on the a-amino-3-hydroxy-5- methyl-4-isoxazol propionic acid (AMPA)/kainate (KA) subtype of glutamate receptors, a positive modulatory effect on g-aminobutyric acid (GABAA) receptors, a use- and time-dependent blockade of voltage-activated Na-channels, a negative 2+ modulatory effect on a neuronal L-type highvoltage- activated Ca -channel (L-type HVACC), and an inhibitory effect on carbonic anhydrase isozymes. Epilepsy is one of the most common neurological disorders. Oxidative stress due to generation of mitochondrial ROS is strongly implicated in seizures in the disorder. It has been demonstrated that TPM modulate the antioxidant enzyme system and has features that make it attractive as a potential neuroprotective agent. In this work, We explored, for the first time, the in vitro ROS scavenger activity of this drug. TPM exhibited trapping activity of superoxide radical-anion ● (O2 ), hypochlorous acid (HOCl) and hydroxil radical (HO) in comparison with several known radical scavengers. These results indicate that TPM possesses antioxidant in vitro potential. INTRACEREBRAL ADMINISTRATION OF PENICILLIN-G MODIFIES BENZODIAZEPINE, MU-OPIOID AND MUSCARINIC RECEPTORS BINDING IN RAT BRAIN: AN 1,3 2 AUTORADIOGRAPHY STUDY. Carmona-Aparicio Liliana , Martínez-Cervantes Adrián , 3 1 2 and Rocha Luisa . Instituto Nacional de Pediatría; Instituto Nacional de Psiquiatría; 3 Departamento de Farmacobiología, Cinvestav-IPN. The epilepsy is an alteration characterized by excessive electric activity of the brain. The 40% of the cases of epilepsy are originated in the temporal lobe. The study of this syndrome has derived in diverse experimental models. One of these is the penicillin G intracerebral administration, in which has not yet determined whether benzodiazepine mu-opioid and muscarinic receptors are modified. Aim: To evaluate the in vitro levels of union of the benzodiazepine, mu-opioid and muscarinic receptors in rat brain areas, during the interictal period after the repetitive administration of penicillin G into amygdala nucleus. Methodology: Male Wistar rats (300g) daily were administered with penicillin G (50 UI, 1 l) in the basolateral amygdalae nucleus through a cannula with a bipolar electrode. The control group was manipulated like before group and saline solution (1 l) was administered. The electrographic recordings were realized before and after injection. The animals were sacrificed 24 h after last administration and the brains were processed with in vitro autoradiography studies and benzodiacepine, mu-opioid and muscarinic receptors were evaluated in different brain areas. Results: The epileptic focus (basolateral amigdalae nucleus) was confirmed through an electrographic recording and was associated with behavioural changes. In the autoradiography studies in epileptic focus a significant decrement (p<<0.05) of benzodiazepine (59%), mu-opioid (39%) and muscarinic (41%) receptors were found during interictal period. However, the results in other brain areas are different. Conclusion: The benzodiazepine, mu-opioid and muscarinic receptors are involved in the seizures induced by intraamygdaline administration of penicillin G in rat. 76 EXTRACELLULAR LEVELS OF EXCITATORY AND INHIBITORY NEUROTRANSMITTERS ARE MODIFIED BY INTRACEREBRAL REPETITIVE ADMINISTRATION OF PENICILLIN-G: AN IN VIVO MICRODIALYSIS STUDY. Carmona1,3 2 3 1 Aparicio Liliana , Martínez-Cervantes Adrián , and Rocha Luisa . Instituto Nacional de 2 3 Pediatría; Instituto Nacional de Psiquiatría; Departamento de Farmacobiología, CinvestavIPN. Human temporal lobe epilepsy is a chronic neurological disease. The study of this pathology has derived in diverse experimental models, between them, the seizures induced by intraamygdaline administration of penicillin G. However, the basic neurochemical mechanisms those underlying these convulsions are unknown. For this reason, we evaluated the in vivo extracellular levels of alanine, aspartate, glycine, glutamine, glutamate and taurine in the amygdalae epileptic focus, after the intracerebral repetitive administration of penicillin G. Methodology: Daily the male rats (Wistar, 300-350 g) of experimental group were administered with penicillin G (50 UI, 1 l) in the basolateral amygdalae nucleus through a cannula with a bipolar electrode. The control group was manipulated like before group and saline solution (1 l) was administered. The electrographic recordings of the ipsilateral and contralateral amygdalae were realized before and after injection. In the 7th day (last day of administration) extracellular levels of neurotransmitters were evaluated in the epileptic focus through microdialysis studies. Results: The epileptic focus (basolateral amigdalae nucleus) was confirmed through an electrographic recording. The experimental group showed that the extracellular levels of alanine (22%), glutamate (27%), glycine (22%) and taurine (18%) in the epileptic focus were decreased, whereas glutamine (13%) showed an increase. Aspartate had no change. Conclusion: Our results suggesting that the excitatory and inhibitory neurotransmitters are released during the seizures induced by intraamygdaline administration of penicillin G similarly to interictal changes that are observed in the human epileptic focus. RELATIONSHIP BETWEEN OXIDATIVE STRESS AND GLYCOSYLATED HEMOGLOBINA1 IN DIABETES MELLITUS INDUCED BY STREPTOZOTOCIN AND TREATED WITH ROSMARINUS OFFICINALIS. Sandra Carrillo Ibarra, José Luis Alvarado-Acosta, Claudia A. Reyes-Estrada y Patricia Yahuaca-Mendoza. Programa de Doctorado en Farmacología, U.A. de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, México. E-mail: [email protected] Diabetes Mellitus (DM) has been considered a public health problem, this based on the prevalence has been increasing until today. Its importance lies not only hyperglycemia, but in its consequences, increasing the risk of death from heart disease, cerebrovascular disease and renal failure, among others. Since in type II diabetes has shown the presence of oxidative stress, is essential to study its relationship to some indicator that constitutes the most representative measurement of blood glucose: glycated hemoglobin. Besides this, research on the abatement of oxidative stress represents a new fitomedication alternative adjunct in the management of DM. In the present study we evaluated the effect of Rosmarinus officinalis on oxidative changes and levels of Hb-A1, in a DM streptozotocin-induced model (65 mg/kg, dissolved in 0.01 M citrate buffer pH 4.5), and pre-dosing of 230 mg/kg of nicotinamide in 0.9% saline,both via IP. We measured fasting glucose, Hb-A1 and oxidative stress markers among others, in the absence and presence of R. officinalis to evaluate their antioxidant activity in the model. The results showed a gradual increase in blood pressure, similar to the increase in blood glucose levels (average levels above 600 mg / dL) and Hb-A1. Related to this, lipoperoxidation increased significantly, which was prevented when the animals received the dose of extract of R. officinalis, which had an antioxidant and partial metabolic control. This effect showed a modest decline in blood pressure and some metabolic disorders. The use of antioxidants as an alternative therapy for diabetes mellitus appears to be promising. Project funded by SEPPIFOP 2002-33-04 and Fondo Sectorial SEP-CONACYT, Ciencia Básica, CB-2008-0-105986 77 COMPOUND DETECTION AND TOXICITY EVALUATION OF ORGANIC EXTRACT OF 1 2 THE ERYTHRINA CORALLOIDES Castañeda Antonio D , Rosales Herrera J.M. , Blas 3 4 1 1 1 Castillo J. Hernández Aldana F. , Jiménez Salgado T. , Tapia Hernández A. Laboratorio 2 3 de Microbiología de Suelos, Facultad de Ciencias Químicas, Colegio de Ingeniería 4 Ambiental, Centro de Química. Benemérita Universidad Autónoma de Puebla. Ed. 103J 2º. piso Centro en Investigaciones en Ciencias Microbiológicas. C.U., Jardines de Sn Manuel Puebla, Pue. Tel. 01 222 2295677 Mexico counts with the Erythrina Coralloides whose components contain certain concentration of alkaloids which have poisonous properties and can induce paralysis disorders in the motor nerves either by its oral ingestion or by its intravenous administration, in phytotherapy. In the present research, the acid and alkaline extraction of its flower and seed had been made, evaluating the composition of the extracts by gas chromatography/mass spectrometry and their toxicity under the FEUM criterion by systemic MGA-DM 3083 injection with CD1 Mouse strains. The mixture obtained contains importance as an agonist: therabaine, oripavine, erysodine whose concentration values are estimated in abundance by the chromatogram obtained. The results shows that the seed is the part which contains a higher concentration of alkaloids followed by the corolla, and finally by the cup. The more efficient extractions were obtained in the acidic compounds, which could be used as precursors of more potent substances to treat pain, like morphine, by other simplified routes. The LD50 obtained is 3.99 mg/ 0.3 mL in mice by intravenous administration. The symptoms presented in the study group were paralysis of tail, hind limp prostration, convulsions, spasms and respiratory depression with hypothermia. At concentration of 266.38 mg/ml, the instantaneous death occurs. MODIFICATION OF THE INVOLVEMENT OF CYCLOOXYGENASE WITH AGE IN THE CONTRACTILE EFFECT OF PHENYLEPHRINE IN RAT AORTA. Castillo-Hernández MC, Guevara-Balcázar G, Velez-Rensendiz JM, López-Canales J. Castillo-Henkel C. Laboratorio de Farmacología Cardiovascular. Departamento de Posgrado e Investigación. Escuela Superior de Medicina IPN. The aim of this paper is to analyze the changes of cyclooxygenase involvement in the contractile response to phenylephrine in the thoracic and abdominal aorta of prepubertal young and old rats. During development there are changes in the activity of some enzymatic pathways, so particular in this work we analyze the change in the involvement of cyclooxygenase in the contractile effect of phenylephrine with age. Cyclooxygenase is significantly involved in the release of prostanoids that regulate the effect of various agonists as in the case of phenylephrine, but not known that how this enzyme is involved during the development of the rat cardiovascular level. In this experimental model we used male rats of 6, 16 weeks and 1 year of age. Rats were anesthetized with pentobarbital (50 mg / kg), after that we proceeded to obtain the thoracic aorta and abdominal aorta. The aortic rings were placed in an isolated organ system which keeps the tissue in physiological Krebs solution at a temperature of 37 ° C and bubbled with carbogen (95% O2 and 5% CO2). Then we proceeded to make concentration response curves to phenylephrine (10-9 to 10-5M) in the presence and absence of indomethacin (COX antagonist). Results showed differences in participation of this enzyme in the contractile response to phenylephrine age-dependent rat 78 RELAXATION CHANGES IN THE THORACIC AORTA AND CORONARY ARTERIES IN THE GENE MUTANT MICE SGCD (B6.129 SGCDTM1MCN) Castillo-Hernández MC*, # & Castillo-Henkel C*, De los Santos S , Guevara-Balcázar G*, Rosas-Vargas H , Coral,# Vázquez RM* *Departamento de Posgrado e Investigación. Escuela Superior de Medicina, & # IPN. Unidad de Investigación Médica en Genética Humana, IMSSS. CMN 20 de Noviembre, ISSSTE. México, D.F. [email protected] The lack of delta sarcoglican is associated with structural and physiological changes in vascular smooth muscle and skeleton muscle, it has been implicated in limb girdle muscular dystrophy and cardiomyopathy .Its has been shown in important way, that the relation between endothelia dysfunction and cardiovascular disease, however it has not related with vascular dysfunction associated to limb girdle muscular dystrophy and cardiopathy, in order to analyze the participation of the nitric oxide and prostacyclin on this experimental model of delta-sarcoglican null mice.In this protocol we use female mice Knock-out and wild type from 5 months old, it were anesthetized with pentobarbital (50 mg/kg IP) and heparine (50 UI), after that we proceeded to dissect the aorta and heart. Both the aorta and heart were placed in an isolated organ system, which keeps krebs solution, and bubbled with carbogen (95% O2 and 5% CO2). Finally we proceeded to make curves concentration response to -9 -5 -9 -6 acetilcoline (10 - 10 )and sodium nitroprusiate (10 - 10 ).We obtain differences in the coronary pressure and aorta relaxation with acethilcoline between Knock-out and wild type mice, in other hand the relaxation to sodium nitroprusiate not show differences in the thoracic aorta between knock-out and wild type mice, unlike we have differences in the coronary pressure with sodium nitropusiate.Our results suggest changes in the relaxation independent of endothelium in artery coronary but not in thoracic aorta, although both vessels show differences in the relaxation dependent of endothelium. EFFECT OF CAPTOPRIL PRE-HYPERTENSIVE THERAPY ON BOTH EXPRESSION AND FUNCTION OF ANGIOTENSIN II AT1 RECEPTORS IN SHR KIDNEY. Castro-Moreno Patricia, López-Guerrero Juan Javier, Ibarra-Barajas Maximiliano, Villalobos-Molina Rafael. Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM. Hypertension targets small and large arteries as well as organs, such as heart and kidney. The effects of the angiotensin-converting enzyme (ACE) inhibitor captopril on angiotensin II (Ang II) AT1 receptor expression, and Ang II-induced contraction was assessed in isolated kidneys from pre-hypertensive and adult spontaneously hypertensive (SHR) rats. Five weeksold SHR and Wistar Kyoto (WKY) rats were treated with captopril at 30 mg/kg/day in drinking water for 2 or 14 weeks. Captopril therapy did not modify systolic blood pressure in WKY rats and avoided its increase as SHR aged. Interestingly, captopril increased Ang II-induced pressor response in isolated kidney of SHR rats after 2 weeks treatment; whereas it diminished basal perfusion pressure in SHR rats 14 weeks after, and drastically reduced Ang II-elicited pressor response. Captopril therapy did not modify pD 2 values (≈ 6.0) for Ang II at 2 and 14 weeks in all rat groups. AT 1 receptor relative abundance was similar between WKY and SHR at both ages. The ACEi diminished AT 1 receptors in SHR kidney cortex (P < 0.05) after 2 weeks, and increased it at longer time; while the agent did not modify AT1 receptor in kidney medulla in none of the rat groups. Data indicate that captopril influences both expression and function of AT 1 receptors in kidney of pre-hypertensive and adult SHR rats, probably avoiding AT1 receptor expression by blockade of angiotensin II synthesis. Keywords: Captopril, AT1 receptors, Hypertension, SHR, Isolated kidney 79 PLASMA LEVELS OF CLOZAPINE AND NORCLOZAPINE IN MEXICAN 1,2 1 SCHIZOPHRENIA PATIENTS Castro Nelly , González-Esquivel Dinora , Custodio 1 1 1,2 1 Verónica , Rojas-Tomé Susana , and Jung Helgi Instituto Nacional de Neurología y 2 Neurocirugía, México. Facultad de Química, Universidad Nacional Autónoma de México (UNAM), México. The aim of the present study was to determine the prescribing practice for clozapine as well as the plasma levels of clozapine and its main metabolite norclozapine in Mexican patients. A prospective study was performed in 69 in and out psychotic patients taking clozapine. Blood samples were taken at steady state. Plasma concentrations of clozapine and norclozapine were determined by HPLC. Results showed that the mean daily dose administered was 250 mg/day. Demographic variables as weight, gender and age were not significant. Plasma levels showed a large interindividual variability and were significant higher in patients under treatment with fluoxetine. Mean plasma levels were 411.3 + 328.12 ng/mL, for clozapine and 172.0 + 129.9 ng/mL for norclozapine. When data were compared with those reported in other populations, it was found that although the dose was lower than that reported in Caucasians, the plasma levels were similar. As a result, the predictive models for the estimation of clozapine concentration in Caucasians were not appropriate for its application in Mexican patients. The findings suggest ethnic differences in the ratio dose/plasma levels of clozapine in Mexican patients. Further studies are required to expand the observations. RESOLUTION AND ANTICONVULSANT ACTIVITY OF THE ENANTIOMERS OF DL-HEPP 1 1 1 Cervantes-Espinoza José G. , Buendía-Pazaran José G. , de la Cruz-Marín Amelia , Vargas1 2 3 Fernández Eugenia , Peralta-Cruz Javier , Chamorro-Cevallos Germán , Meza-Toledo 1 1 2 3 Sergio E. . Departamentos de Bioquímica , Química Orgánica y Farmacia , Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. Carpio y Plan de Ayala, CP 11340 México D. F, México. Epilepsy is a brain disorder that is characterized by recurrent seizures that affects 1% of the population worldwide. Despite the antiepileptic drugs (AEDs) available, at present 30% of patients with epilepsy continue to have seizures and, even among those considered controlled many unpleasant side effects are still endured. There is clearly a need for more and better AEDs. The compound DL-3-hydroxy-3-phenylpentanamide (DL-HEPP) protects mice and rats against seizures induced by pentylenetetrazol (PTZ), maximal electroshock (MES), bicuculline, 4-aminopyridine, thiosemicarbazide, hippocampal kindling, gammaaminobutyric acid withdrawal syndrome and against the focal spike activity in the genetic absence epilepsy rats of the Strasbourg model. However, the differences in biological activity between the enantiomers of DL-HEPP have not been studied. In this work we report the resolution of the compound DL-HEPP and the anticonvulsant evaluation and neurotoxicity of its enantiomers. The enantiomers of DL-HEPP were prepared by resolving the (-)-brucine and (-)-1-phenylethylamine salts of the acids. The optically active acids were then esterified with diazomethane and reacted with ammonia to give (+) HEPP and (-) HEPP. Optical purity of the amides was greater than 99 % enantiomeric excess determined by chiral HPLC. Pharmacologically, DL-HEPP and its enantiomers have a similar significant anticonvulsant activity against PTZ induced seizures in mice, but in the MES test, the anticonvulsant activity of DL-HEPP and its enantiomers was different. In the rotarod ataxia test the neurotoxicity of DL-HEPP and its enantiomers was similar, but a variation in time between the enantiomers was found with the anticonvulsant activity in the PTZ model. Phenobarbital was used as the reference drug. 80 DL-3-HYDROXY-3-ETHYL-3-(3’-TRIFLUOROMETHYLPHENYL) BUTYRAMIDE, A NEW 1 2 ANTICONVULSANT Cervantes Espinoza José Gabriel , Peralta Cruz Javier , Meza Toledo 1 1 2 Sergio Enrique Departamento de Bioquímica, Departamento de Química Orgánica Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional., Prol. de Carpio y Plan de Ayala, Casco de Santo Tomás, CP 11340 Mexico D.F. Epilepsy is one of the most common neurological disorders affecting around 0.5% of the worldwide population. In Mexico the incidence is calculated around 15 persons per 1000. Approximately 70 to 80% of the patients with epilepsy are successfully treated with present antiepileptic drugs (AED), however 20 to 30% of epileptics are refractory to antiepileptics, hence the need to develop new AED. The molecule DL-3-hydroxy-3-ethyl-3-phenyl propionamide (DL-HEPP) is an anticonvulsant showing a broad spectrum of activity. Incorporation of hydrophobic groups in the phenyl ring of DL-HEPP increased its anticonvulsant activity. Therefore, a hydrophobic group (CF 3) has been introduced in the phenyl ring of DL-HEPB to give fluorobencenamide DL-CF3-HEPB. This compound was prepared using a Stobbe condensation between 3’-trifluoromethyl propiophenone and diethyl succinate to give the hemiesters, which were treated with hydrobromic acid to produce DL-5ethyl-5-(3’-trifluoromethylphenyl) butyrolactone. The lactone was treated with aqueous 1 13 ammonia to give DL-CF3-HEPB, which was characterized through H-NMR , C-NMR and IR spectroscopy. The results obtained confirmed the structure proposed. The anticonvulsant activity was determined using pentylenetetrazol (80 mg/kg) via intraperitoneal (i.p.) in male Swiss-Webster mice. The effective doses 50 obtained via i.p. for DL-CF3-HEPB, its nonhalogenated analogue (DL-HEPB) and phenobarbital were 10, 63 and 8 mg/kg respectively. In conclusion the inclusion of the trifluoromethyl group in the phenyl ring of DL-HEPB increased its antoconvulsant activity. DEVELOPMENT AND VALIDATION OF A LIQUID CHROMATOGRAPHY METHOD TO QUANTIFY MIDAZOLAM IN A NEW ORAL FORMULATION FOR PEDIATRIC USE. Juan 1 1 1,2 Luis Chávez Pacheco , Brianda López Aviña , Janett Flores Pérez , Eunice Sandoval 1 1,2 1 3 Ramírez , Hugo Juárez Olguín , Blanca Ramírez Mendiola , José González Zamora , Ángel 4 1 Changin Guerra , Carmen Flores Pérez , 1. Laboratorio de Farmacología, Instituto Nacional de Pediatría. 2. Departamento de Farmacología, Facultad de Medicina, UNAM. 3. Servicio de Cirugía y Anestesia, INP. 4. Chocolates Turín, SA de CV. Midazolam is a short-acting benzodiazepine commonly used to induce anaesthesia or sedation in children. In Mexico, a commercial oral pediatric formulation of midazolam is not available yet and it is usually administered by mixing the parenteral solution with apple juice; this formulation has the disadvantage of having a bitter and unpleasant flavour. In the present work, we developed and validated an HPLC method to quantify midazolam in a new white chocolate formulation. The stability of this formulation was evaluated at different storage conditions and a preliminary assay of relative bioavailability was carried out in healthy -1 volunteers. The method of quantification was linear in the range of 5 to 60 µg mL .The midazolam amount in the formulation remained stable for 90 days at 4 and 40°C (in the dark) while at 25°C was stable only for 14 days (exposed to light). The relative bioavailability assay suggests that our preparation of midazolam in white chocolate reaches plasma levels and induces pharmacologic effects compared to those induced by the apple juice formulation. This new white chocolate formulation masks the unpleasing flavour and has a more attractive presentation to the paediatric patient, which may be useful for children sedation and to ease its management by health carers. 81 COGNITIVE IMPAIRMENT IN RATS AFTER UNILATERAL 6-OHDA LESION IN 1,3 1 THALAMIC RETICULAR NUCLEUS. Chuc-Meza E , Avila-Velarde G. , Guarneros1 1,3 2 1,3 1 Bañuelos E. , Miranda-Rivera O. , Limón D. , García-Ramírez M. ; Dept. of Physiol. , 2 Natl.Sch. of Biol. Sci., I.P.N., DF 11340, México; BUAP, Puebla, México. Thalamic Reticular nucleus (TRn) has been involved in regulation of afferents to thalamiccortical loops participating in attention process. TRn receives dopaminergic innervation, shared with striatum and globus pallidus, from substantia nigra compacta (Anaya-Martinez et al, 2009), and we have reported an anxiolytic effect induced by bilateral 6-OHDA lesion of TRn (Picazo et al, 2009). This effect was assigned to alterations on detection of stimuli need it to elicit anxiety responses. If this is true other behavioral aspects interrelated to anxiety as memory process could be affected by this lesion. Because the inter-hemis-pheric connection of both TRn, we probed unilateral lesion by local administration of 6-OHDA in a group of male Wistar rats. Right lesion was confirmed by ipsilateral turning behavior induced by systemic apomorphine 8 days post-surgery and by microscopic observation of brain slices. Anxiolytic effect was searched in Elevated Plus Maze test (EPM) and tasks used to explore alterations in cognitive performance were New Object Recognition test (NOR), 8-Radial Arm and Morris water mazes (RAM & MWM, respectively). Hemi-lesioned rats compared with sham group had a lesser percent time in open arms in EPM, in NOR showed a minor ratio of time exploring the novel object, in RAM the acquisition was slower and in the retention phase they had more reference errors and in MWM they showed a larger latency to find the platform in the first assays of acquisition phase. So, unilateral 6-OHDA lesion replied the anxiolytic effect of bilateral lesion of TRn and besides unrevealed cognitive deficiencies in memory consolidation. 3 Funded by fellowships COFFA-IPN & PIFI MOLECULAR MODELING APPLIED TO STUDY CONSEQUENCES OF POLYMORPHISMS IN LIGAND RECOGNITION OF HUMAN Β1 AND Β2 1 1,2 1 ADRENOCEPTORS. Ciprés-Flores FJ , Soriano-Ursúa MA , Amezcua-Gutiérrez MA , 1,3 1,2,3 1 2 Trujillo-Ferrara JG , Correa-Basurto J . Departamentos de Bioquímica, Fisiología3 Farmacología y Laboratorio de Modelado Molecular y Bioinformática, Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México ([email protected]). Human β-adrenoceptors (h-βAR) are seven-transmembrane domain proteins. The study of polymorphisms in the h-β1AR and hβ2-AR subtypes is an attractive point due to its association of these polymorphisms with disease or differences in the treatment-response. Also, some h-βAR polymorphisms are shared with the β adrenoceptors of animal species which have different response to specific ligands comparatively to human (like frog (Xenopus Laevis) or pig (Sus scrofa) species). The most representative polymorphisms for h-β1AR are Arg389Gly and Ser49Gly, which are associated a higher prevalence of heart disease than subjects with wild type h-β1AR. While, representative polymorphisms for h-β2AR are Asn27Glu and Arg16Gly, which are associated with asthma and response of treatment of this disease. We built 3-D models of h-βAR with/without the above mentioned polymorphisms. These models were energetically optimized with NAMD 2.6 program. Then, we analyzed the ligand recognition by docking methods with Autodock4 program. Molecular modeling studies of polymorphic h-βAR showed differences in ligand affinity and recognition mode than its respective wild type. 82 CYCLIC NUCLEOTIDE-GATED CHANNELS PARTICIPATE ON THE CAPABILITY OF FERTILIZATION OF MAMMALIAN SPERM Abraham Cisneros and Daniel Sánchez. Cinvestav, Unidad Monterrey, N.L. México. Mammalian sperm, in his transit through the female genital tract, acquire the ability to fertilize the egg in a process called capacitation. During this event, the intracellular levels of cAMP and cGMP increase, suggesting that cyclic nucleotide-gated (CNG) channels, which have been identified in mammalian sperm, play a functional role in their physiology. Here we report an electrophysiological characterization of the effect of cyclic nucleotides on capacitated and non-capacitated mouse sperm. Using the patch-clamp technique in the whole-cell configuration, we show that macroscopic ionic currents augment with the capacitation in around a 100%, and that the addition of both, 8Br-cAMP and 8Br-cGMP, also increase the macroscopic current of non-capacitated sperm. Furthermore, based on dose response curves, we found differences in the sensitivity to the nucleotides, obtaining a K1/2=100M for 8Br-cGMP and K1/2=230M for 8Br-cAMP, showing a higher affinity for 8Br-cGMP. On other hand, although cyclic nucleotides regulated the activity of CNG channels may also be activating other protein entities, so to clarify the participation of CNG channels, we used Lcis-diltiazem (50M), a specific inhibitor of these channels, observing a partial blockade of more than 30% of inward currents and more than 50% of outward currents, suggesting that CNG channels are a fundamental part of the signaling pathways that confers the fertilization capability to mammalian sperm. LEARNING COMPONENTS AND SCHOLAR ACHIEVEMENT IN PHARMACOLOGY: IT’S IMPACT IN MEDICAL GRADUATE EXAMINATION. Eusebio Contreras and Sandra Castañeda. Facultad de Medicina, UNAM Facultad de Psicología, UNAM. CP O4510. [email protected] The planning of teaching-learning activities and process in Pharmacology could be supported by knowledge about students characteristics. With the purpose to find out a possible profile of successful students at Medical School at Universidad Nacional Autonoma de Mexico (campus CU), we studied some academic and personal variables and its short-term and longterm influence over knowledge domain at the end of medical school. Variables studied: 1) Diagnostic test of high school knowledge at beginning of Medical School, high school attended before Medical School, 2) Basic knowledge test when starting pharmacology nd course, 3) Student achievement in Pharmacology, 4) Assigned group in 2 . Year of Medical School (when Pharmacology is taken), 5) Medical graduate examination achievement, 6) Learning and self-regulation strategies explored through the inventory ―Estilos de aprendizaje y orientación motivacional-dimensión frecuencia‖ (Castañeda,1995) at first month of second year. The convenience sample was composed by 68 students: 34 men and 34 women, selected from five groups. Results showed: 1. Significative differences in the diagnostic test at beginning of Medical School in regard to attended high school, 2. Significative differences in scholar achievement of Pharmacology depending on group where students belong by registration (groups are chosen by students depending on their average grades).3.Significative differences in scholar achievement of Pharmacology depending on the opinion of students about studying materials.4. Correlation between Pharmacology grades and grades in medical graduate examination at expected time of graduation (terminal efficiency).5. Other Learning and self-regulation strategies that were analysed, did not show differences on achievement results in Pharmacology, nor on medical graduate examination. 83 EFFECT in vitro AND in vivo OF THE ETHYL ESTER OF N-BUTYL OXAMATE ON THE FERTILITY OF MOUSE SPERMATOZOA. Cordero-Martínez, J*., Wong, C y RodríguezPáez L. Departamento de Bioquímica de la Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional. Prol. Carpio y Plan de Ayala. C.P. 11340, México D.F. Tel. 57 29 6000 Ext. 62321. *e-mail: [email protected] The aim of the present study was to inhibiting the fertilizing capacity of the spermatozoa mouse using a oxamate derivative, the N-butyl oxamate, a selective inhibitor of lactate dehydrogenase-C4 (LDH-C4), that is a specific isoenzyme from testes and spermatozoa. We used a prodrug of N-butyl oxamate, which was the ethyl ester of N-butyl oxamate. We performed assays on motility, viability and acrosome reaction in mice spermatozoa in absence and presence of different concentrations of the ethyl ester of the N-butyl oxamate. We found that this prodrug inhibited all the parameters before mentioned, and in the screening of the results, we found a concentration-dependent effect. Furthermore, on spermatozoa extracts, we measured the activity of LDH-C4 and another glycolytic enzymes, the hexokinase 1-S (HK1-S) and glyceraldehyde-3-phosphate dehydrogenase (GAPDS) in presence and absence of different concentrations of the inhibitor to demonstrate the selective effect to LDH-C4. We obtained the concentration that inhibit the 50% of the activity (IC 50) and it was 0.0222 mM for LDH-C4, and 161.98 and 0.6601 mM for the HK1-S and GAPDS respectively. We determined the LD50 that it was of 693.30 mg/kg, this result clasifies the ethyl ester of the N-butyl oxamate as a few toxic substance. We assayed the effect of the inhibitor in vivo and we found that this inhibitor diminished the motility of mice spermatozoa, without affecting the activity of the LDH-C4. Finally, because all our results, we can suggest the ethyl ester of the N-butyl oxamate can be a target for future studies as a possible male specific contraceptive. EFFECT OF MONOSODIC GLUTAMATE AND KETAMINE IN MOTIVATED BEHAVIOR IN MALE MICE Córdova-Moreno R., Alegría R. P. S., Martínez M. T., Hernández L. L. F., Soto P. C. A., Moreno B. C., Delgadillo G. H. J. Dpto. Sistemas Biológicos. Lic. en Q.F.B., Universidad Autónoma Metropolitana. Xochimilco (UAMX). Glutamate (Glu), most abundant excitatory neurotransmitter in central nervous system, participates in natural (feeding, thirst, sex) and pathologic (addiction and chronic drug abuse) behaviors by means of ionotropic (NMDA, AMPA and Kainate types) and metabotropic glutamatergic (mGluRs) receptors. Glu has been associated with neuroplastic changes, as a consecuence of abuse and relapse to consumption of psychostimulants (cocaine, amphetamine). Chronic drug abuse, produces increasing alterations of dopaminergic and glutamatergic neurotransmission.Pathologic behaviors have been most frequently investigated, by its impact in the health. However, there is not the same interest to study the natural behaviors. So, we decided analized the role of Glu in a natural motivated behavior. To this purpose, we evaluated the effect of the monosodium salt of glutamate, compared to ketamine hydrochloride (non competitive glutamatergic NMDA receptor antagonist), in a model of natural motivated behavior, using a female mice, as a incentive stimuli. Twenty male mice (3 independent groups, 3 animals/group and 1, control, saline solution, 0.9%), 20 to 25 g, CD1, were systemically administered (i.p.) with L-glutamic acid monosodium salt monohydrate at 2.5, 5.0 and 10.0 mg/kg, doses and ketamine at 5.0, 10.0 and 15.0 mg/kg, subanesthetics doses. Time exhausted to find the incentive sitmuli, was measured when the animals were individually put into a radial maze (six arms). This procedure was similar for both treatments, in all of the three experimental tests, and a previous first test, as an indicator of average time (with no drug), was included. Latency was varied at 5, 15 and 30 minutes, each other test, respectively. Not was obtained any time-differences induced by two treatments probed; nevertheless, it was observed a behavioral change evidenced as an ongoing aggressive fighter of the animals, mainly in the L-glutamate acid monosodium salt, group, and also, at 15 mg/kg dose of ketamine-treated animals. 84 ROLE OF THE GLUTAMATERGIC TRANSMISSION IN THE SEXUAL EXHAUSTION 1 2 1 PHENOMENON OF MALE RATS Córdova-Moreno, R., Rodríguez-Manzo, G. Dpto. de 2 Sistemas Biológicos. Universidad Autónoma Metropolitana, Unidad Xochimilco. Dpto. de Farmacobiología. Centro de Investigación y de Estudios Avanzados del IPN. Sede Sur. Sexual exhaustion is a condition of prolonged sexual behavior inhibition resulting from ad libitum copulation of a male with a single receptive female. Twenty-four hours after the satiation procedure, 2/3 of the population of sexually exhausted animals does not show sexual activity and 1/3 copulates to ejaculation, after which, copulation is not resumed. Gutamatergic neurotransmission has a facilitative role in sexual behavior expression of sexually experienced male rats. Sexually exhausted male rats differ in several behavioral aspects when compared to sexually experienced, non exhausted animals. Thus, the sexual behavior facilitative effect of electrically stimulating the medial preoptic area, ventral tegmental area (VTA) and nucleus accumbens is lost in sexually satiated rats. Additionally, they show a generalized hypersensitivity to drugs when compared to non exhausted males. These evidences suggest the occurrence of neuroplastic changes resulting from repeated brain activation during ad libitum copulation. epeated stimulation by chronic drug abuse, promotes neuroadaptations in the mesolimbic system, that include an enhancement of glutamatergic neurotransmission evidenced the blockade of drug abuse reinstatement by glutamatergic antagonists. We hypothesized that glutamatergic receptor antagonists could reverse the sexual inhibition of satiated animals. To this aim, we tested the glutamatergic NMDA receptor antagonist, ketamine, the AMPA/kainate receptor antagonist, 6-cyan-7nitroquinoxaline-2,3-dione (CNQX), and the mGluR5 glutamatergic receptor antagonist, 6methy-2-phenyl-ethynilpiridine (MPEP), administered both systemically (i.p.) or directly into the VTA, origin of the mesolimbic system. Systemic administration of all glutamatergic antagonists facilitated sexual behavior expression in satiated rats, reversing sexual exhaustion at specific dose levels. When intra-VTA injected, only the AMPA/kainate receptor antagonist, CNQX, reversed the sexual behavior inhibition of exhausted animals at dose of 1 µg/rat. Thus, glutamate seems to play opposite roles in the regulation of sexual behavior expression of sexually satiated and sexually experienced male rats. RELATIONSHIP OF BONE MINERAL DENSITY WITH THE NITRIC OXIDE LEVELS AS A MARKER OF OXIDE-REDUCTIVE STRESS AND THE EFFECT OF THE TREATMEN FOR 1 1 OSTEOPOROSIS CÓRDOVA-PÉREZ N , BASURTO-ACEVEDO L , VÁZQUEZ MARTÍNEZ 1 2 2 1 AM , ORDOÑEZ JL , ARENAS-TÉLLEZ JM , ZÁRATE-TREVIÑO A . ENDOCRINE 1 RESEARCH UNIT , NATIONAL MEDICAL CENTER, INSTITUTO MEXICANO DEL 2 SEGURO SOCIAL, SCHOOL OF MEDICINE TOMINAGA NAKAMOTO . Introduction: The osteoporosis causes a great impact on the Mexican population due to it’s health and economic implications. The osteoporosis keeps a relatively high prevalence in direct relationship with the age. Risk factors that influence the osteoporosis are smoking, obesity, sedentary and oxidative stress. Recent studies have shown that both the oxidative stress plays an important role in the bone loss, and also, that the antiosteoporotic drugs can decrease the oxidative stress levels in postmenopausal patients with osteoporosis. The objective of this study was to determine the concentrations of nitric oxide as a marker of oxidative stress and its relationship with bone mineral density in postmenopausal women. Methods: Forty-three postmenopausal women were recruited with an age range between 40 to 65 years old in postmenopausal established early stage and diagnosis of osteopenia/osteoporosis. All women were treated with strontium ranelate, 2 g/day orally; thereafter DEXA bone densitometry and nitric oxide determinations were carried out to 3.6 and 12 months of treatment. Results: We found significant decrease in the nitric oxide concentrations between control group and patients treated with strontium ranelate at 12 months, confirmed by bone densitometry 85 NANOPHARMACEUTICAL TECHNOLOGY FOR ANTITUMOR IMMUNOREGULATORY 1 1 2 1 PURPOSES. Corona-Ortega T. , Weiss-Steider B. , Soto-Vázquez R. , Rangel-Corona R. Laboratorio de Oncología Celular (1) y Laboratorio de Tecnología Farmacéutica (2). FESZaragoza. UNAM. E-mail: [email protected]. The lymphocyte growth factor Interleukin 2 (IL-2) has proven to be effective in the therapy against human tumors by activating the immune system, in particular the cytolytic Tlymphocytes (CTLs) and killer cells. Nevertheless, the systemic delivery of IL-2 has been limited by its high toxicity. In this respect nanoparticles constitute an interesting tool for in situ IL-2 delivery. Our work group has shown that several cervical cancer cells express, like lymphocytes, the IL-2 receptor (IL-2R) on their membranes. Recently we had reported the construction of a nanocarrier structure that expresses non-covalently bound IL-2 on its external surface that renders the particle susceptible to be attached to IL-2R-bearing cells. Our hypothesis for antitumor activity resides in the fact that the IL-2 bearing nanocarrier could promote close proximity of lymphocytes and tumor cells by the fact that both posses the IL2R. Then if the close proximity of tumor cells with lymphocytes mediated by our nanoparticles could favor the recognition of a putative tumor antigen by the IL-2 activated lymphocytes a cytolytic activity could be induced. Our results demonstrated that in fact these nanoparticles did bind to cervical cancer cells that express the IL-2R, making them in turn IL-2 presenters that attracted blood lymphocytes and induced tumor cell lysis. Thus we can speculate that the IL-2 bearing nanocarrier attached to the IL-2R on the tumor cell and then before it was endocytized attracted lymphocytes, also through their IL-2R, acting as a bridge between tumor cells and lymphocytes that favored the recognition of tumor antigens and thus induced the antitumor response obtained. (Grant PAPIIT 220108) SPHINGOSINE 1-PHOSPHATE-INDUCED VASOCONSTRICTION IS INCREASED IN THE ISOLATED PERFUSED KIDNEYS OF DIABETIC RATS Israel Coronel, Abraham Arellano, Horacio Osorio, Martha Franco, Rocío Bautista-Pérez. Department of Nephrology, Instituto Nacional de Cardiologia ―Ignacio Chavez‖[email protected] Introduction: It has been reported that S1P constricted renal and mesenteric microvessels in vitro and reduced renal and mesenteric blood flow in vivo, which can also alter tubular function. Based on these finding, we investigated the identity of the receptor subtype that mediates renal vasoconstriction in isolated perfused kidneys of diabetic rats. Methods: Renal vascular tone was evaluated in the isolated perfused kidneys of control and diabetic rats. To determine the renal vascular response to S1P and the contribution of the S1P 1, S1P2 and S1P3 receptors, we determined the dose response (0.05, 0.1, 0.2, 0.4, 0.8 and 1.5 ng) to S1P before and after of the administration of VPC23019, JTE-013 or CAY10444 (antagonist of S1P1/3 , S1P2 ,S1P3 receptor respectively). Results: A bolus injection of S1P produced dosedependent renal vasoconstriction in the isolated perfused kidneys of control and diabetic rats, but the vasoconstriction was greater in the kidneys of diabetic rats compared with the kidneys of control rats (18.67±1.3, 30±4.1, 58±7.7, 91±9.1, 120± 8, 144±0.1 vs 4± 0.1, 6.400±0.9, 13.60± 2.0, 32± 4.6, 49.33±2.6, 66 ±2 mm Hg). The S1P-induced renal vasoconstriction was only inhibited by JTE-013 in both experimental groups. These results demonstrate that, in the isolated perfused kidneys of diabetic rats, the S1P induced renal vasoconstriction through the S1P2 receptor. In addition, we observed increased expression of the S1P 2 receptor at the mRNA and protein levels in the kidneys of diabetic rats compared with those of controls Conclusion: In the present study, we have shown that S1P induces renal vasoconstriction through the S1P2 receptor and that antagonists of this receptor may have potential as drugs to control diabetes-induced vascular complications. Acknowledgment: This project was supported by a Mexican Council of Science and Technology (CONACYT) Research Grant (No. 60979) awarded to R.B.-P. 86 (PRO)RENIN RECEPTOR EXPRESSION LEVELS WHEN CAPTOPRIL OR LOSARTAN ARE ADMINISTRATED IN NEPHRECTOMIZED RATS. Cruz-Laguna Erika Yadira, VargasRobles Hilda, Mendez-Tenorio Alfonso, Escalante-Acosta Bruno Alfonso Department of Biomedicine, CINVESTAV and Department of Biochemistry, ENCB-IPN, Mexico City, Mexico Recent studies have found that (pro)renin receptor ((P)RR) has a crucial role in the development and progression of renal damage. However, there is very few information about the expression of this receptor in models of chronic kidney disease and its expression patterns when drugs for hypertension are used.. The aim of this study was to determinate the expression levels of (P)RR, and other RAS molecules in the remaining kidney of subtotally (5/6) nephrectomized rats (5/6 NFX) treated with anti-hypertensive drugs. Male Wistar rats two months old, were randomly assigned to the following groups: sham operated n=5, 5/6 NFX rats n=5, 5/6 NFX rats administrated with captopril (50 mg/Kg/day) (NFX+captopril) n=5, 5/6 NFX rats administrated with losartan (10 mg/Kg/day) (NFX+losartan) n=5. The drugs were oral administrated and animals were followed-up for 60 days. Protein in 24-h urine was measured at weeks 2, 4, 6 and 8 after surgery. At day 60 systolic blood pressure was assessed by aorta cannulation, rats were sacrificed to obtain: plasma for the determination of Ang II and Ang 1-7, and renal tissue for the evaluation of expression levels by quantitative PCR. Blood pressure was significantly increased in the NFX group compared with the other groups (199.77 ±9.62 p < 0.01). Levels of Ang II (1.0729 ±0.2381 pmol/mL p<0.01) and Ang 1-7 (4.009 ±2.399 pmol/mL p=0.015) change significantly in the NFX group compare with the other groups. (P)RR expression level were significantly increased in remnant Kidney of the NFX group (1.68-fold p=0.05) compared with the sham operated. In the NFX+captopril and the NFX+losartan groups the (P)RR expression levels were higher (8.3-fold and 4.4-fold respectively p=0.05). CARDIOVASCULAR DISORDERS IN ACUTE MYOCARDIAL INFARCTION AND REPERFUSION IN DOG AND RABBIT. PRELIMINARY STUDY OF AN ANTIOXIDANT TO PREVENT RECCURRENCE IN THE COURSE OF THE DISEASE. Raúl E. Cuevas Durán, Patricia Yahuaca Mendoza, Adrian Reyes López y José Luis Alvarado Acosta. Programa de Doctorado en Farmacología. U.A. de Medicina Humana. Universidad Autónoma de Zacatecas. Zacatecas, México. Acute Myocardial Infarction (AMI) is conceived as an episode of ischemia, necrosis and/or myocyte death. In this condition are induced important changes on electrocardiogram (EKG), blood pressure (BP), another phenomenon immediately after AMI, is the reperfusion, which generates oxidative stress, In this work we studied, comparatively in dog and rabbit, the changes occurred during experimental AMI-reperfusion and the effect of Rosmarinus officinalis extract in order to know if the antioxidative action can modify the alterations postIAM. AMI was induced in dogs. At open chest, we proceeded to occlude the left coronary artery; ischemia was maintained for 90 min and after released artery occlusion, reperfusion was 120 min more. New Zealand rabbits, were exposed to the same procedure, but, both coronary occlusion and reperfusion were kept by 35 min; EKG and BP were obtained. During AMI, in dog, EKG showed elevation of the P wave, ST-segment depression and ventricular extrasystoles. Five dogs died by ventricular fibrillation. During reperfusion was also present A-V dissociation and ventricular tachycardia. Systolic and diastolic pressures suffered a fall of about 50% compared to control, without significant alteration of heart rate (HR). In the rabbit model, were prolonged the PR-interval, and the QRS and QT segments by 37%, 73% and 31% respectively. Changes occurred in ST segment and drop in systolic and diastolic pressures during reperfusion. In experimental AMI, I.P. administration of Rosmarinus officinalis extract (antioxidant), at the beginning of reperfusion, avoids the presence of cardiac rhythm disorders. Experimental models of acute myocardial infarction in dogs and rabbits are suitable for the study of compounds that could to reverse or prevent cardiovascular alterations in the course of the disease. Project funded by Fondo Sectorial SEP-CONACYT, Ciencia Básica. Code CB-2008-01-105986 87 EFFECT OF SELECTIVE COX-2 INHIBITOR AND CCK ANTAGONIST IN DIABETIC 1 1 1 2 RATS. De la O-De la O E , Mandujano-Morales JA , Juárez-Rojop IE , Ortega-Varela F , 3 3 2 4 Tovilla-Zárate CA , Jiménez-Santos A , Aguilar-Mariscal H , Flores-Murrieta FJ , Bermúdez3,5 1 2 3 Ocaña DY . UJAT-DACS, Villahermosa, Tabasco. UMICH, Morelia, Michoacán. UJAT4 5 DAMC, Comalcalco, Tabasco. INER, D.F., México. Hospital de Alta Especialidad Dr. Gustavo A. Rovirosa Pérez, Villahermosa, Tabasco. Celecoxib is a selective COX-2 inhibitor with potent anti-inflammatory and analgesic properties. The use of this drug has been shown to be effective in reducing inflammatory and neuropathic pain following peripheral nerve injury in rats. On the other hand, CCK antagonist has been reported produce peripheral antinociception by itself. The objective of this study was evaluated the effect of celecoxib and a non-selective CCK antagonist in diabetic rats. Experiments were performed on male Wistar rats of body weight range 280–320 g. Diabetes was induced following a streptozotocin injection (60 mg/kg, i.p.). Diabetes was confirmed 3 days after injection by measurement of tail vein blood glucose levels with the Accu-Check blood glucose monitoring system. The paw withdrawal threshold was determined by the updown method of Dixon and Chaplan et al. Allodynia was considered to be present when paw withdrawal thresholds were 4 g. Diabetic rats not demonstrating allodynia were not further studied. Four weeks after diabetes induction we evaluated a dose-response curve for intraperitoneal administration of celecoxib (0.3, 3, 10, 30 mg/kg) and proglumide (20, 40, 60, 180 mg/kg), respectively. This drugs reduced increased the withdrawal threshold. Results suggest that a selective COX-2 inhibitor and CCK antagonist combination could reduce allodynia in diabetic neuropathy. Supported by PROMEP, grant UJAT-PTC-064 EFFECT OF THE INFUSION OF Morinda citrifolia L. (NONI) ON THE CLINICAL COURSE 1 OF DIABETES MELLITUS INDUCED WITH ALOXAN. Del Bosque de la Barrera, F., 1 1 1 1 1 Galván-Morales, D., García-Ruíz, M., García-Saucedo, B., Miranda-Torres, A., Rangel1 1 2 1 Suárez, G., Fregoso-Padilla, M., Barrera-Escorcia, E. & Velasco-Lezama, R. Facultad de 2 Estudios Superiores Iztacala (FES-Iztacala), UNAM. Departamento de Ciencias de la Salud. Universidad Autónoma Metropolitana-Iztapalapa. México, D.F, [email protected] In natural medicine Morinda citrifolia (noni) is used for the treatment of Diabetes Mellitus type 2 (DM2), hyperglycemia and kidney damage associated or not to DM2. The fruit and infusion of the leaves of the plant have been used by their hypoglycemic properties. The purpose of this study is to determine the effect of the infusion of the leaves of M. citrifolia on the blood level of glucose in hyperglycemic rats. Infusion of the plant was prepared (4 g/l) as a treatment for clinical picture of DM, using 13 Wistar rats distributed in three groups; a) healthy, b) diabetics without treatment, c) diabetics treated with the infusion of noni, with 5, 4, 4 rats, respectively. Diabetes was induced with aloxan (120 mg/kg). Determinations of blood glucose were performed every week during four weeks; also, glucose and protein in urine were determined. Intake of food and fluid, body weight, and excretion of urine twice a week, were measured for three weeks. From second week rats resisted the treatment with aloxan, they did not presented hyperglycemia, Glucose and protein in urine and their excretion and consume of water were higher in rats treated with aloxan. Records mention that aloxan may cause kidney damage that along with the diuretic effect of noni could increase the renal failure. This is reflected in our results by the amount of urine excreted, consume of liquid, that were higher in groups treated with noni. It is concluded that the infusion of leaves of noni has no hypoglycemic effect even in healthy animals and presents a diuretic effect which can lead to serious complications when kidney damage is present. 88 OXYDATIVE STRESS IN A MURINE HYPERGLYCEMIC MODEL MODULATED BY ROSMARINUS OFFICINALIS. Fátima E. Del Muro-Casas, José Luis Alvarado-Acosta y Patricia Yahuaca-Mendoza. Programa de Doctorado en Farmacología, U.A. de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, México. E-mail: [email protected] The health problems of diabetes mellitus (DM), which occurred worldwide, and metabolic complications favored by oxidative changes encountered during the process, demanding continued studies to ensure proper management of the oxidation state present in condition of chronic hyperglycemia, particularly the evaluation of some treatment with antioxidants such as those from Rosmarinus officinalis. In this study we used two experimental models of hyperglycemia in Wistar rats, evaluated for 8 weeks: 1) induced by sucrose (5%) in drinking water, simulating a pre-DM of hyperglycemia, and 2) streptozotocin (STZ), administered 65 mg/kg, dissolved in 0.01 M citrate buffer pH 4.5 and pre-dosing of 230 mg/kg of nicotinamide in 0.9% saline, both via IP. We measured metabolic indicators (glucose, insulin, glycosylated hemoglobin, cholesterol and LDL) and oxidative stress (lipid peroxidation in liver, pancreas, kidney and heart), as well as monitoring, blood pressure. Our results showed a progressive increase in basal glucose up to 40% of control, doubling the values of Hb-A1, while the change in insulin was not significant and increased LDL. Increased lipid peroxidation in all tissues studied, from week 4 of administration of sucrose. Also blood pressure increased by about 20%. These observed changes were modulated by the presence of R. officinalis, particularly by reducing lipid peroxidation, and preventing changes in LDL. In the STZ model, lipoperoxidation increased mainly in pancreas and kidney, an event that was prevented by the antioxidant action of R. officinalis. This work emphasizes the importance of using an herbal antioxidant to prevent oxidative stress and some of its consequences in experimental DM condition. Project funded by SEP-PIFOP 2002-33-04 and Fondo Sectorial SEPCONACYT, Ciencia Básica, CB-2008-0-105986 * Number 15605 CONACYT Project Fellow. ACADEMIC PRACTICE BY PHARMACEUTICS CHEMISTRY STUDENTS AT THE METROPOLITAN AUTONOMOUS UNIVERSITY, XOCHIMILCO. Delgadillo Gutiérrez Héctor Javier, Moreno Bonett Consuelo, Zugazagoitia Herranz Rosa, Sánchez Martínez Cristina, Córdova Moreno Rebeca. Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Xochimilco. Calzada del Hueso 1100, Colonia Villa Quietud. Código Postal 04960, México D. F. correo E: [email protected]. Advanced students of the Metropolitan Autonomous University of Mexico Xochimilco have the opportunity to make an Academic Practice at Pharmaceutics Industry. The students before and after going to their Academic Practice at the industry make an auto evaluation with the following items: I. Quality Control, II. Pharmaceutical Technology, III. Pharmaceutical Evaluation, IV. Interpersonal Relationship and after Academic Practice the assessor evaluates students in the same items (Assessor Evaluation), also Academic History of the students is compare with the Assessor Evaluation. The measurement scale was from 1 to 10. Results indicated difference between before and after Academic Practice in II. Pharmaceutical Technology, media 8.7 against 8.6 (p < 0.05), also difference were found in Quality Control, media 8.5 against 8.8. There were differences between media students´ Assessor Evaluation and media students’ Academic History, 8.74 against 7.72 (p < 0.01). Students and assessors wrote their impressions about the Academic Practice experience and in both cases the answer was quiet well. It was concluded that students are getting along in their academic practice in the pharmaceutical industry and the assessors are quite satisfied with the students at Metropolitan Autonomous University Xochimilco. 89 EVALUATION OF LEARNING OF CARBOHYDRATES AS SOURCE OF ENERGY IN THE CELL Delgadillo Gutiérrez Héctor Javier*, Saldaña Balmori Yolanda**. *Departamento de Sistemas Biológicos. Universidad Autónoma Metropolitana, Campus Xochimilco. Calzada del Hueso 1100, Colonia Villa Quietud, Código Postal 04960, México D. F. correo E: [email protected]. **Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM). Avenida Universidad 3000, Delegación Coyoacán, Código Postal 04510, México D. F. correo E. [email protected]. Due importance to future health care related to basic science, including Biochemistry, a central and important theme is learning linked with the mechanisms available in production of energy in the cell. This work analyses the results of learning on issues related to carbohydrate metabolism and energy production, students who completed the field of Biochemistry and Molecular Biology at Faculty of Medicine at UNAM during the last 4 school cycles. This study examines the responses of 4,935 students over the years 2006 to 2010 assessed their knowledge departmental partial exams. Issues that divided the study were ten: 1.- Structure and digestion of carbohydrates, 2.- Glycolysis, 3.- Pyruvate decarboxylation 4.- Citric acid cycle, 5.- Gluconeogenesis, 6.- Metabolism of glycogen, 7.- Pentose cycle, 8.Regulation, 9.- Bioenergetics and 10.- Free radicals. The database was collected in Excel and exported to statistical package JMP. Test statistic was a multiple linear regression where the dependent variable was bioenergetics and independents were the other themes; the level of association between the variables was measured with the regression β coefficient. The results indicated that issues influencing the bioenergetics learning were the Citric acid cycle (β = 0.172) and Glycolysis (β = 0.160) and the least influenced were Pentose cycle (β = 0.058) and Structure and digestion of carbohydrates (β = 0.055). The results noted that although all topics learning were significant (p < 0.01) for understanding of bioenergetics, it was concluded that a better understanding of the mechanisms in energy production would be obtained if the assimilation of the other eight themes were similar to that reported by Citric acid cycle. 5-HT2 AND 5-HT3 RECEPTORS PARTICIPATE IN THE ANTINOCICEPTIVE SYNERGISM 1 1 INDUCED BY TRAMADOL PLUS CAFFEINE. Díaz-Reval MI , Carrillo-Munguía N , 1 2 1 Martínez-Casas M , López-Muñoz FJ . Centro Universitario de Investigaciones Biomédicas, 2 Universidad de Colima. Departamento de Farmacobiología, Cinvestav, sede Sur. The pain is a subjective sensation. The mechanisms that transmit the nociceptive sensation are different according to stimulus that causes it. These are some reasons why it is very difficult remove the pain. The combinations of drugs are a tool very useful to handling of pain. It has been reported that in analgesics combinations with different mechanisms may produce a synergistic effect or when analgesics with adjuvant are combined the antinociceptive effect is potentiated. We have reported that caffeine was able to produce a synergistic effect when was combined with tramadol. However the mechanisms are unknown. The objective of this study was determinate the 5-HT2 and 5-HT3 receptors participation in the synergistic effect of tramadol and caffeine combination. The formalin model was used to determinate combination antinociceptive effect either with antagonists or without antagonists. Different groups of animals were administered with tramadol (10 mg/kg), caffeine (3.16 mg/kg) or the combination of both drugs. Other groups received either ondansetron (34 nmol, i.c.v.) or ketanserin (34 nmol, i.c.v.) after were administered with tramadol, caffeine or the combination (tramadol 10 mg/kg + caffeine 3.16 mg/kg). The results showed that ketanserin inhibited antinociceptive potentiation 66%, while ondansetron inhibited 41%. On the other hand, the same antagonists were not able to inhibit antinociceptive effect neither tramadol nor caffeine when they were administered alone. In conclusion, these results suggest that serotoninergic pathway participate in the antinociceptive synergism induced by co-administration of tramadol and caffeine, through 5-HT2 and 5-HT3 receptors. 90 FLUORIDE EXPOSURE INCREASE CARRAGEENAN-INDUCED INFLAMMATION AND MECHANICAL HYPERALGESIA IN RATS AND THESE EFFECTS ARE NOT REVERSED BY DICLOFENAC. Dibildox-Alvarado E., Aguirre-Bañuelos, P. Facultad de Ciencias Químicas de la Universidad Autónoma de San Luis Potosí. México Fluoride is considered an essential trace element, however exposure to more than 1 ppm cause toxic effects. Fluorosis is the mayor manifestations of chronic poisoning from long-term exposure and is a serious health exposure in many parts of the world. Biochemical changes in fluorosis have been reported by many researches. Higher concentrations of fluoride are known to affect antioxidant defense system; brain and muscles by inhibit some enzymes associates with energy production and transfer membrane transport, synaptic transmition. Added to these facts, we are found that exposure of fluoride increase the carrageenaninduced inflammation and mechanical hyperalgesia in rats. For this propose we used rats that received distilled water for drinking while the others rats received distiller water with 5, 15 and 50 ppm of sodium fluoride from the polypropylene bottles. After 6 months, the animals were tested by carrageenan-induced inflammation and mechanical hyperalgesia models. Significantly higher inflammatory and mechanical hyperalgesic responses were observed proportionally with fluoride concentrations. These mechanical hyperalgesia and inflammation increases were not reversed with an anti-inflammatory non steroidal drug (diclofenac 100 mg/Kg v.o.). The mechanisms about fluoride increases mechanical hyperalgesia and inflammation are poorly understood, but, with these results we suggested that fluoride could be induced an over production of reactive oxygen species, more that a COX enzymatic effect. THE QUALITY OF COMPOUNDED SOLID DOSAGE FORMS CONTAINING CARBAMAZEPINE: A BIOEQUIVALENCE STUDY IN HEALTHY VOLUNTEERS Estela 1 2,3 2 Dibildox , Aurigena Antunes de Araújo , Lílian Grace da Silva Solon , Gerlane Bernardo 3 1,4 1 4 Coelho Guerra , Maricela Martinez-Delgado , Abraham Escobedo , Irma Torres-Roque , 5 1 1 Amador Covarrubias , José Pérez-Urizar . Facultad de Ciencias Quimicas, Universidad 2 Autonoma de San Luis Potosí, San Luis Potosí, México.; Post-graduation in Pharmaceutical 3 Science of Federal University of Rio Grande do Norte (UFRN) Natal, RN, Brazil; Department 4 of Biophysics and Pharmacology of UFRN, Natal, RN, Brazil; Dixpertia Investigación 5 Biofarmacéutica y Farmacologica S.C., San Luis Potosí, México. Instituto de Investigación Clínica de Occidente S.A. de C.V., Guadalajara, México. Extemporaneous compounding medicines in Brazil are economically important, but they are associated with a number of clinical, safety and ethical issues. The safe interchangeability of generic or reference products by compounding products requires that they prove to be truly bioequivalent. Currently the bioavailability of several compounding medicines remains unknown. Thus, the aim of this study was to evaluate the bioequivalence of two extemporaneous capsules formulations of 200-mg carbamazepine. The bioavailability of compound capsules (purchased from two compounding Pharmacies) as well as reference ® product (Tegretol ), were compared through a single-center, open, randomized, single-dose, 2-period crossover, 2-sequences pilot assay, with a 2-week washout interval using 12 healthy volunteers. Blood sampling was performed during 72-h after dosing. The carbamazepine showed slow absorption from all products tested, but the maximum plasma concentration was achieved faster with the compounded capsules. Statistical analysis of the AUC 0-t suggested that reference and both tested products were bioequivalent. Nevertheless, the AUC0-∞ of both tested drugs was lower than reference due to differences in the final elimination phase. Although two compounded carbamazepine formulations showed similar ® concentration-time profiles to Tegretol , further studies with larger sample size are necessary to confirm the bioequivalence and interchangeability. 91 ANTI-HELICOBACTER PYLORI, ANTI-ULCEROGENIC AND ANTI-EDEMATOGENIC ACTIVITIES OF CYRTOCARPA PROCERA. Wendy Itzel Escobedo-Hinojosa, Karina García Martínez, and Irma Romero. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, C.P. 04510, México, D.F., México. Cyrtocarpa procera stem bark is used in Mexican folk medicine for the treatment of gastrointestinal diseases. Helicobacter pylori is the major etiological agent of chronic active gastritis, peptic ulcer disease, and is linked to gastric carcinoma. The increasing resistance of H. pylori to antibiotics demands the search for novel compounds. This work evaluates the in vitro anti-H. pylori effect of the organic extracts (hexane [H], dichloromethane [D], dichloromethane:methanol (1:1) [D-M], and methanol [M]) obtained from C. procera stem bark, against H. pylori ATCC 43504 by the broth dilution method. The pharmacological action spectrum (determined by the TPA- induced acute ear edema, and ethanol-induced acute gastric ulcer models), and acute toxicity (Lorke test) of the organic extracts, in CD-1 mice, were also evaluated. The results showed that H extract (MIC: 7.8 µg/mL) showed the highest inhibitory effect against H. pylori, followed by D, D-M, and M extracts The pharmacological studies showed that the M, and H extracts possesses significant (p≤0.05) gastroprotective effect in terms of the length and number of gastric ulcers, with a maximum of gastroprotection at 300 mg/Kg (86.4% and 82.5% for M and H extract, respectively). The topical application of H, significantly reduced (p≤0.05) the acute ear edema induced by TPA with a ED 50=2.15 mg/ear. Acute toxicity studies showed that all the extracts were safe, with LD 50> 5000 mg/Kg. Results confirmed the great medical potential of this plant, as well as its promising use in the development of an integral treatment of H. pylori related diseases. This work was partially supported by DGAPA-UNAM (IN 225711-3). PHARMACOEPIDEMIOLOGY OF HEADACHE IN A UNIVERSITY POPULATION OF MEXICO Escobedo-Moratilla A., Fragoso-Morales L., Pérez-Urizar J. Facultad de Ciencias Químicas, UASLP Mexico 50 % of world population has occasionally headache episodes, being stress and nervous tension the most common trigger factor. Because of lack of data about epidemiological, clinical and pharmacological aspects of headache in young adults in Mexico, the aim of this study was to explore these parameters in a student university population. A questionnaire was applied during the period of November-December of 2009 in different schools of the Universidad Autónoma de San Luis Potosí with n=292 and 99.99 % confidence level. The average age was 19.94 ± 2.00 years. 72.6 % of the participants have suffered at least one headache episode during the last year. The most frequent trigger factors were: stress and nervous tension (85.62 %), too little sleep (78.08 %), missed meals (73.97 %). The most frequent therapies were: acetilsalicilic acid (51.08 %), paracetamol (27.42%), ketorolac (5.91 %). These results shows high headache incidence in this young population in San Luis Potosi, México. 92 ANTIOBESITY EFFECT OF RESVERATROL IN AN EXPERIMENTAL MODEL OF DIETINDUCED OBESITY IN RATS. Escobedo-Moratilla A., Vargas-Morales JM., Pérez-Urizar J. Facultad de Ciencias Químicas, UASLP Mexico Obesity is a disease that importantly afflicts millions of people in Mexico and in the world. Resveratrol (RVT) is a dietary supplement with antioxidant properties that are still little known, but some studies show its effectiveness to treat obesity, diabetes and high blood pressure, among others. Several therapies for the treatment of obesity are available (pharmacologic and non pharmacologic), being frequent the prescription of two or more treatments at the same time, mainly due to the diversity of diseases that accompany and side-effects produced by the ingestion of drugs. The aim of this study was to investigate the effect of resveratrol on the prevention of the increase in weight in an experimental model of obesity induced by hypercaloric diet in rats. Groups of 6 animals were fed ad libitum with a standard diet (C-(-)), hypercaloric diet (C-(+)) or hypercaloric diet + resveratrol 10 mg/kg p.o. t.i.d. (RSV) during 3 weeks in which follow-up was given to body weight. The weight difference in rats with hypercaloric diet was 84.83% over the 62.48% of the standard diet, which represented an increase of 35.8%, enough to consider that the experimental model applies to test treatments against morbid obesity. Considering the weight gain in C-(+) as the maximum observed effect (Emax obesity), we calculated the effect antiobesity as the proportion of not achieved Emax obesity with RSV, which was of 31.09% (p < 0.05). These results suggest that the consumption of RSV can contribute in the pharmacological treatment of obesity. PRESCRIPTION FOR ANTIBIOTICS. NEW LEGISLATION IN MEXICO Espinosa-Meléndez 1 2 2 3 1 M.T , Medrano-Morales J. , Saracho-Alarcón A, Alvarez de la C.C. . Department of 2 3 Pharmacology, Department of Dental Clinic. Department of Ethics. Faculty of Dentistry, National University of Mexico The theme of the World Health Day 2011 is based on strategies to control antimicrobial resistance. This has also been the concern of the World Health Organization (WHO) since th 2001 and of the World Medical Association in its 48 General Assembly in South Africa in 1999 where the Declaration on Resistance to Antibiotics was made. In Mexico, as well as in other Latin-American countries, the antimicrobial resistance and auto medication are public health problems. The objective of this paper is to summarize the legislation that different institutions have made to rule the prescription of antibiotics in Mexico. COFEPRIS, stands for Comisión Federal Para la Protección contra Riesgos Sanitarios (Federal Commission to th Prevent Sanitary Risks) published, on the 27 may 2010, agreements to determine the rules to sell antibiotics, ratificating the Article 226, IV fraction, of the General Law of Health, stating that antibiotics must be sold only with the exhibition of the prescription. This agreement is mandatory since august 25, 2010. The Reglamento de Insumos para la Salud (Health Consumables Regulation) includes: Article 30: the prescription must contain the name and presentation of the drug, route of administration, frequency and lenght of the treatment. Article 31: drugs that appear in the Catalog of Generic Drugs must be prescribed by generic name and, if desired, by commercial name. Article 32: public institutions must prescribe using only generic names. Article 33: drugs that have in its tag the note: ―prescription is needed‖ can not be sold without prescription, even though, before 2010, antibiotics had this legend and were sold without prescription. COFEPRIS established requirements for the drugstores that are not clear yet, so different drugstores understand them in different ways, making the acquisition of antibiotics difficult for the patients in Mexico. 93 PHYTOCHEMICAL ANALYSIS OF THE NATURAL JUICE of Kalanchoe gastonis bonnieri and Kalanchoe flammea WITH HUMAN SPERM AGGLUTINATION AND 1 1 2 IMMOBILIZATION Fajardo Peregrina S.*; Miranda Beltrán M. L.; Huacuja Ruiz L. 1 Laboratorio de Fitofarmacologia. Centro Universitario de los Lagos, Universidad de Guadalajara. Av. Enrique Díaz de León 1144, Col. Paseos de la Montaña. Lagos de Moreno, 2 Jalisco, México Instituto de Enfermedades Crónico Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No 850, Col Independencia, 43100, Guadalajara, Jalisco, México The plants of the genus Kalanchoe belong to Crassulace family, comprising 200 species. Of these plants have reported various biological activities due to the presence of different secondary metabolites in these species. The objective of this project is to present the natural juice phytochemical analysis of Kalanchoe gastonis bonnieri (K. gastonis bonnieri) and Kalanchoe flammea (K. flammea) with immobilizing and agglutinating activity of human spermatozoa. METHODS: Obtaining the natural juice of the species K. gastonis bonnieri and K. flammea. We performed in vitro biological activity of these juice (sperm). For identification of secondary metabolites of these species were different techniques: determination of polyphenols, flavonoids, saponins, tannins, triterpenes, terpenoids, glycosides and DPPH radical scavenging. RESULTS: Although the species K. gastonis bonnieri and K. flammea belong to the same species concentration and the presence of various secondary metabolites change. The concentration of polyphenols for K. gastonis bonnieri and K. flammea was (56 414 mg / g and 57,878 mg / g). In these species, the concentration of flavonoids was (2825 mg / g and 2,775 mg / g), as well as identification tests showed increased presence of isoflavones in K. gastonis bonnieri and flavones and flavonols in K. flammea. There was major concentration of saponins in K. bonnieri gastonis that K. flammea. In both species was the presence of tannins, triterpenes and glycosides. However, these plants do not have terpenoids. The radical scavenging activity was major in K.flammea compared to K.gastonis bonnieri. CONCLUSION: Secondary metabolites (flavonoids) found in these species conferring the agglutination and immobilizing the sperm and possibly could have other biological activities as presented in the other species of the same family. PHARMACOKINETIC VARIATIONS OF ACETAMINOPHEN IN ACUTE RENAL FAILURE RATS José Manuel Fallas y María Estela Meléndez. Departamento de Farmacia, ENCB-IPN. Mexico. Introduction: acetaminophen (APAP) is one of the most used drugs around the world. Its safety, efficacy and pharmacokinetics are closely related with normal function of kidney and liver. However, no information is available regarding the right dose to be used in animals with acute renal failure (ARF). Method: adult female Wistar rats (200 ± 20 g b.w.) were used and 2 groups were formed, control group and ARF-group. Acute renal failure was induced with a single dose of potassium chromate (20 mg/kg, subcutaneous). In urine and blood samples obtained on days 1, 3, 5 and 7, creatinine and sodium concentrations were measured. In urine, proteins and glucose were also measured and urinary flow calculated. PAH uptake by cortical renal tissue was determined. A second experiment was carried out, and APAP (15mg/kg/dose) was intraperitoneal administrated to rats with previous ARF induction and control rats, for 3 days each 12 hours, beginning on day 2 after ARF induction. Blood was collected from each animal and APAP concentrations were determined in plasma using a colorimetric method and pharmacokinetic parameters, elimination half life time (t½), area under the curve (AUC) and clearance (Cl) were calculated in both ARF and control groups. Results: in ARF, results revealed proximal renal function altered, increased creatinine serum and decreased glomerular filtration rate. In the APAP pharmacokinetic parameters a significant increase in t½ (from 3.95±0.29 to 32.12±0.29 hours) and AUC (from 5.31±0.39 to 43.18±1.22 mg•min/mL) meanwhile, a significant decrease in clearance (from 0.55±0.01 to 0.066±0.0005mL/min) were observed in ARF rats and control group, respectively. Conclusion: the acetaminophen pharmacokinetic shows significant modifications in ARF rats. 94 HIBISCUS (Hibiscus sabdariffa) CALYCES EXTRACTS EXHIBITS ANTIPYRETIC 1*, ACTIVITY Bertha Fenton Navarro 2 2 1 María Elena Velázquez Hernández , Blanca Nateras 3 1 Marín , Alvaro Rodríguez Barrón , Luz Torner Aguilar , Humberto Ruiz Vega . 1.-Posgrado, Facultad de Medicina UMSNH 2.-Facultad de QFB, UMSNH. 3.CIBIMI, IMSS. *Email: [email protected]. Pyrexia or fever is defined as a rise in body temperature, controlled by the hypothalamus. The systemic response is initiated when an organism is invaded by pathogens that evoke an internal response mediated by cytokines. Generally Hibiscus calyces are used to make cold and hot beverages, sweet jams, creams and candy. Also to treat different ailments. Objective: Evaluate the antipyretic effect of extracts from Hibiscus and correlate them with cytokine circulating levels. Material and Methods: Male Wistar rats were distributed in 5 treatment groups: negative (saline), positive (acetaminophen), Hibiscus crude extract, Hibiscus proteins and Hibiscus pigments. Fever was induced with subcutaneous injections of 20% brewer’s yeast, 16 hrs later the treatments were administrated orally. The temperatures were measured at the following times 0, 30, 60, 120, 180 and 240 min. Then blood was obtained by hart puncture. The cytokine levels were measured using ELISA kits. Results: The negative saline group maintained fever. A significant decrease in temperature levels was present with the rest of the groups. The interleukin 6 (IL-6) showed an increase and it is related with the decrease observed in the rest of the cytokines measured (IL-1, TNFα, INFƴ). Concussion: The Hibiscus fractions studied exhibit antipyretic activity with modifications in the cytokine levels. RELEASE OF NYSTATIN NANOEMULSIONS VERSUS REFERENCE FORMULATION Fernández, F; Mallandrich, M; Clares, B; Lazaro, R; Flo, A; Calpena, AC. Biopharmaceutical and pharmacokinetics department. University of Barcelona. (Spain) Pharmaceutical technology department. University of Granada (Spain) Nystatine (nys) is an antifungical compount effective against mycetes of Candida species. In comparison to classical dermal formulations, the nanoemulsions are effective vehicles systems for transdermal drug delivery, due to its colloidal structure and its high drug loading. The aim of this study is to evaluate the release of nistatin nanoemulsion as previous step to the transdermal permeation assay. The nanoemulsion was elaborated with, Labrasol®, Plurol oleique®, Labrafac lipophile®, Propylenglycol as excipients in different proportions. Compounds were stirring by ultrasounds under cold. The particle size was measured by Zeta-Sizer, Malvern Instruments. As reference formulation was used Myscostatin® cream, not available in the market at present. Release studies (n=6) were carried out with vertical diffusion cell of 2.54cm2 and cellulose membrane (MWCO 14 kDa). A mixture of methanol:dymetilformadime:water (55:15:35 v/v) was used as receptor phase at 32ºC. Samples were withdrawn at different time point scheme for 46h and quantified by means a validated HPLC method. The mobile phase was water:ACN (60:40) with 1% acid acetic at 0.8ml/min flow rate and wave length 305nm, a Kromasil® C18 (5 used. Retention time of nys was 4.1min. Release amounts of nys from nanoemulsions and reference formulation were evaluated by non-linear regression by means WinNonLin®. Data shown a faster nys release from the nanoemulsion compared with the cream. Further studies will be carry out in order to check if the retained amounts of nys in the skin will ensure the efficacy of the nanoemulsion for the treatment of topical candidiasis. 95 VALPROIC ACID MODULATES BRAIN PLASTICITY THROUGH EPIGENETIC CHROMATIN REMODELING IN THE BLIND RAT: IMPLICATIONS FOR HUMAN SIGHT RECOVERY. Fetter-Pruneda I, Olivos-Cisneros L, Díaz D, Padilla-Cortés P, Báez-Saldaña A, Gutiérrez-Ospina G. Department of Cell Biology and Physiology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Visual deficits constitute a major social and financial burden to health systems worldwide. The World’s Health Organization estimates that 45 million people experience blindness associated with metabolic, infectious, oncologic, congenital, genetic or accidental conditions. Given the importance of the visual world for guiding human daily live activities, major efforts have been made to restore visual abilities in the blind. Unfortunately, most measures aimed at procuring visual restoration have failed in providing the patient with a functionally efficient visual system. This problem may be related with the fact that the visual cortex is recruited to process somatosensory and auditory information in the blind, rendering it inaccessible to the restored visual inputs. Therefore, the study of the mechanisms and their modulation, underlying cortical reorganization in the blind, surely will improve our chances of designing knowledge-based interventions that could restore more effectively visual functions. Accordingly, we studied the mechanisms by which the primary somatosensory cortex (S1) expands in blinded rats. We found that early blindness reschedules S1 development as evidenced through anatomical and cellular parameters. These changes occur together with an earlier process of neuronal histone deacetylation. By administering valproic acid -a histone deacetylase inhibitor- through the milk on a daily basis, we have successfully prevented S1 expansion and delayed its formation in early blinded animals. Therefore, valproic acid may become a potential drug for procuring epigenetic modulation of brain plasticity, a circumstance that may improve the probability of achieving visual recovery in blind subjects before the implantation of visual prosthesis. EFECT OF ANGIOTENSIN (1-7) AFTER 24 AND 48 HOURS OF MYOCARDIAL INFARCTION Flores M .Jazmín*, Valencia H. Ignacio**, Martínez A. Luisa* FES Cuautitlán UNAM*, Escuela Supeior de Medicina IPN** Introduction: The renin-angiotensin system plays a critical role in heart attacks; Angiotensin (1-7) by itself inhibits the activity of the ACE, it antagonizes AT1 receptors, releases bradykinin, stimulates the release of nitric oxide and prostanoids. Objective: Determine the contractile effect of Ang I and Ang II in rat aortic rings after 24 and 48 hours of coronary occlusion, to assess the activity of Ang-(1-7). Methods: We used Wistar rats, which had a ligature on the left coronary artery for 24 and 48 hours. We obtained the aortas and prepared them as follows: small rings were cut and suspended (3 grams tension) in an isolated organ chamber containing warm (37º C) buffered solution, continuously aerated (5% CO2 and O2 95%), the rings were allowed to equilibrate for 1 h. Then the rings were -4 incubated for 20 minutes with L-NAME 10 M. As with Ang-(1-7) with the addition of the first. -12 -6 Dose-response curves of Ang I and Ang II (10 -10 M) of the control group and groups with infarct were obtained. Results: The response to Ang I and Ang II of the groups of 24 and 48 h showed a decrease in the contraction when incubated with Ang-(1-7) while those where LNAME was present, there was no difference. Also the no-infarction group shows that in spite of absence of NO, a decrease of contraction was observed. Conclusions: Vasodilation generated by Ang-(1-7) after the stroke, is dependent on NO while without infarction it is independent. PAPIITIN224310-3 GVC-20. 96 A RELIABLE METHOD OF LIQUID CHROMATOGRAPHY FOR THE QUANTIFICATION OF ACETAMINOPHEN AND IDENTIFICATION OF N-ACETYL-P-BENZOQUINONEIMINE 1 1 (NAPQI), ITS TOXIC METABOLITE Carmen Flores-Pérez , Juan Luis Chávez-Pacheco , 1 1 1 Fernando Eguiarte Sólomon , Blanca Ramírez-Mendiola , Liliana Rivera Espinosa , Hugo 1,2 1,2 Juárez-Olguín , Janett Flores-Pérez 1. Laboratorio de Farmacología, Instituto Nacional de Pediatría. 2. Departamento de Farmacología, Facultad de Medicina, UNAM. Acetaminophen is basically metabolized in the liver by conjugation with sulfate- and glucuronide (>90%), and 5 to 9% is oxidized leading to the formation of N-acetyl-pbenzoquinoneimine (NAPQI), which has been reported as responsible of acetaminophen toxicity. The aim of the present study was to develop a simple, selective and reliable method to quantify acetaminophen and its metabolite NAPQI for therapeutic monitoring of both compounds using 100 mL plasma samples, by reverse phase HPLC and UV detection. The assay was performed using a C18 column and an isocratic elution with water–methanol– formic acid (70:30:0.15; v/v/v) as mobile phase. Linearity of the method was assayed in the range of 1–30 mg/mL for acetaminophen and 10–200 mg/mL for NAPQI, with a correlation coefficient r = 0.999 for both compounds, and inter- and intra-day coefficients of variation of less than 13%. Several commonly co-administered drugs were analyzed for selectivity and no interference with the determinations was observed. The detection and quantification limits for acetaminophen and NAPQI were 0.1 and 1 mg/mL, and 0.1 and 10 mg/mL respectively. Therefore, the present method can be used to monitor acetaminophen levels using very small volume of plasma, which may be helpful when patients are newborns. Besides, this method is also able to detect the NAPQI in patients diagnosed with acetaminophen intoxication. A DIET RICH IN POLYUNSATURATED FATTY ACIDS PREVENTS THE METABOLIC DISORDER CAUSED BY TYPE I DIABETES. Franco-Colín M., Servín-Santos J. E., and Cano Europa E. Departamento de Fisiología de la Escuela Nacional de Ciencias BiológicasIPN. México, D.F. [email protected] Diabetes is a public health problem in Mexico and its incidence has increased. This disease mainly affects energy metabolism, which can be improved by a daily diet polyunsaturated fatty acids (PUFA). To prove whether a diet rich in polyunsaturated fat improves the metabolic state in type I diabetes we used 20 rats of Sprague-Dawley rats were divided into 4 groups: 1) normoglycemia (n = 5), 2) normoglycemia + 30% PUFA (n = 5), 3) diabetes (n = 5) and 4) diabetes + 30% PUFA (n = 5). The type I diabetes was induced by administration of 50 mg/Kg ip of streptozotocin. The animals received the diet for 15 weeks and during the treatment they were measured for body weight, water consumption and energy intake per week. At the end of the diet the animals were sacrificed and epididymal, retroperitoneal and mesenteric adipose tissues were obtained. The diabetic animals showed an increase in caloric intake, polydipsia, weight loss and a decrease in adipose tissue. While in diabetic animals fed diet rich in PUFA had a reduced caloric intake, polydipsia and this treatment prevents the weight loss. So, a diet rich in polyunsaturated fatty acids enhances the metabolic state of rats with type I diabetes. Funded by grants from the SIP-IPN 20100727 and 20110527. 97 CYTOTOXIC AND NO MUTAGENIC ACTIVITY OF NOVEL HETEROCYCLIC COMPOUNDS IN HUMAN CERVICAL CELL LINES. Frías González Susana, Escutia Calzada Daniel, Abrego Reyes Víctor H., Angeles Aguiano Enrique, Romero Rojas Andres and Ordaz-Pichardo Cynthia. Escuela Nacional de Medicina y Homeopatía del IPN, México. Cervical Cancer (CeCa) is a serious disease developed as consequence of cellular changes into the tissue connecting uterus and vagina. This disease is the second place of women deaths in developing countries. Among the current cancer treatments, chemotherapy has demonstrated be effective even in late stages of cancer. However, the cytotoxicity of antiproliferative drugs is still causing severe secondary effects to cancer patients making necessary the creation of new and less aggressive drugs. A series of novel heterocyclic compounds have been synthesized using computer-based modeling. Here, we evaluated the cytotoxic activity of a series of heterocyclic compounds in several human cervical cancer cell lines. In vitro cytotoxic effects were tested with MTT assay and Crystal Violet staining. Among the target cells (HeLa, SiHa, Ca Ski and C-33 A), the cell lines Ca Ski and C-33 A were sensitive to a piperidinic compound (LQM 335) while HeLa and Ca Ski cell lines were sensitive to a cupper complex (LQM 402) showing IC 50 values under 100µM. In addition, these compounds were less cytotoxic against no tumorigenic cells (PBMC and CHO). Three compounds out of the total series were selected in order to evaluate the mutagenic effect in a bacteria model. The mutagenic effect of three selected compounds was determined using Salmonella typhimurium strains for detection of frame shift mutations (TA98), base-pair substitutions (TA100), and free radical damage (TA102) in the Ames test. None of the tested compounds showed mutagenic activity in these strains. Therefore, according to our results, the cupper complex may be a good candidate for anti-cancer drug development and further evaluation is necessary. The posible mechanism of cellular damage is being evaluated for the compound LQM 402, as well as the effect of this compound into a in vivo model. OPIOID RECEPTOR DISTRIBUTION IN HUMAN CORTEX OF PATIENTS WITH MESIAL a b TEMPORAL LOBE EPILEPSY. Christian L Frías-Soria , Mario Alonso-Vanegas , José M b a a Cisneros Franco , Cecilia Zavala-Tecuapetla , Luisa Rocha Department of Pharmacobiology. Center of Research and Advanced Studies. Mexico City, Mexico National Institute of Neurology and Neurosurgery ―Manuel Velasco Suarez‖, México City, Mexico Current evidence supports the view that opioid receptors are modified as a consequence of seizure activity in human brain and experimental models of Mesial Temporal Lobe Epilepsy (MTLE). The aim of this study was to evaluate the binding to κ opioid receptors (KOP-R) in neocortex of patients with pharmacoresistant temporal lobe epilepsy through in vitro 3 autoradiography using [ H]U-69593. Temporal neocortical tissue was obtained from patients with MTLE (n=10). Control samples were obtained from autopsy of 8 subjects without history 3 of neurological disease. [ H]U-69593 binding in fmol/mg protein for autopsy tissue was as follows: layers I-II, 14.1±3.1; layers III-IV, 11.1±3.9; layers V-VI, 86.3±42.5. In contrast with 3 autopsy samples, the neocortex from MTLE patients demonstrated enhanced [ H]U-69593 binding in layers V-VI (979%, p<0.05). No significant differences on binding were detected in cortical layers I-II and III-IV. The present study provides strong evidence that MTLE is associated with alterations in KOP-R, situation that could be involved with the mechanisms leading to pharmacoresistant epilepsy in this patients. CONACyT Grant # 98386 and Scholarship # 232612 98 CALMODULIN ANTAGONISTS INHIBIT THE SEA URCHIN SPERM HYPERPOLARIZATION NECESSARY FOR DIRECTED MOVEMENT TOWARDS THE EGG. Blanca Estela Galindo. Centro de Investigación y de Estudios Avanzados del IPN. Unidad Monterrey. Egg peptides from egg-jelly surrounding the sea urchin egg, profoundly influence sperm physiology. A sperm activating peptide, named speract, a decapeptide from Strongylocentrotus purpuratus sea urchin eggs, transiently stimulates a membrane guanylyl + cyclase in the sea urchin sperm flagella and activates a cGMP-dependent and K selective channel (SpKCNG) that hyperpolarizes the sperm. This hyperpolarization is essential for the directed movement of sperm towards the egg. OBJECTIVE: To determine if calmodulin (CaM), which has been found in the sperm of various species, participates in the signal transduction induced by speract. METHODS: Membrane potential recordings with fluorescent dyes in sperm flagellar vesicles were used. RESULTS: The vesicle hyperpolarization induced by speract was inhibited by the calmodulin antagonists: TFP, mastoparan, W-7, W-5 and W12. Since that inhibition occurred at concentration at which calmodulin action is inhibited by these compounds, the overall findings pointed that this protein could be involved in the 2+ speract response. The speract response in flagellar vesicles was Ca independent, we use 2+ the Ca chelators EGTA and BAPTA. Ten millimolar of EGTA does not inhibit the hyperpolarization and BAPTA (2 mM) only inhibited partially. High concentrations of CaMdependent kinase II and phosphatase inhibitors did not alter the response of the flagellar vesicles to speract (Galindo, et al, 2000). CONCLUSION: The overall results indicate that the speract-induced hyperpolarization involves the participation of calmodulin. This work was supported by grant 82831 from Conacyt to B.E.G. ETHNOBOTANIC STUDY OF RANDIA ACULEATA IN THE MUNICIPALITY OF JAMAPA, 1,3 2 VERACRUZ, MEXICO. Carlos Angel Gallardo-Casas , Cynthia Mercado-Hernández , 1 2 3 María Teresa Valadez-Omaña , María Teresa Valenzuela-Vargas , Carlos Castillo-Henkel , 3 1 María del Carmen Castillo-Hernández . [email protected] Academia de 2 Biología CECyT #6 ―Miguel Othón de Mendizábal‖ IPN, Departamento de Morfología 3 ENCB-IPN, Sección de Estudios de Posgrado e Investigación ESM-IPN The objective of this work was to do an ethnobotanic study of Randia aculeata in the municipality of Jamapa, Veracruz, Mexico. The methodology was to poll 75 inhabitants of the region. Out of this number of people polled, 96% of them knew the existence of the plant. In all of these cases people gave general information about the plant which is commonly used as an antidote against venom from snakes, spiders, bees and toads. The plant is commonly used too as a remedy against pain, inflammation, diabetes and cancer. It was found that Randia aculeata is regularly sold in local markets in the region which indicates an important presence in the local economy for these people. We also found the colloquial names used to denominate the plant in the region: ―crucetillo‖ or ―crucetillo macho‖. The most common way to prepare the crucetillo for traditional medical use is to chop 7 complete fruits and leave them immersed in beer or in wine for 8 days. 45 mL of this solution has to be ingested to cure chronic diseases. In case of a sting made by a poisonous animal 250 mL should be ingested immediately after the fact. It can also be used in pets when they bite a poisonous toad by accident. One of the collected specimens of crucetillo was stored in the herbarium of medicinal plants of the Centro Medico Siglo XXI IMSS and was registered for its traditional medical use. 99 ANGIOTENSIN II INCREASED FUNCTIONAL RESPONSE AND VASCULAR HYPERTROPHY INDIRECTLY THROUGH 1D-ADRENOCEPTORS IN WISTAR RATS. 1 1,3 1 2 Itzell A. Gallardo-Ortíz , P. López-Sánchez , J.J. López-Guerrero , J.D. Sánchez-González , 1 1 1 M. Ibarra and R. Villalobos-Molina Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, México. 2 Escuela Militar de Graduados de Sanidad, Universidad del Ejército y Fuerza Aérea, México 3 City, México. Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, México City, México. Angiotensin II (Ang II) has an important function in regulating systemic arterial pressure. The aim of this work was to explore the in vivo Ang II continuous effect on 1D-adrenoceptors functional expression and hypertrophy in aorta and caudal arteries of Wistar rats. Osmotic minipumps (Alzet) filled with Ang II (release of 200 ng/kg/min/14 days) were subcutaneously implanted in 3 months-old male Wistar rats, at the same time rats were administered BMY 7378 (10 mg/kg/day/14days) or losartan (1 mg/kg/day/14days) in drinking water. Arterial blood pressure was measured by a tail-cuff method; after 2 weeks arteries were isolated and used for contractile experiments. Ang II induced an early and sustained increase in blood pressure and a maximal effect at 11 days (136 ± 4 vs 104 ± 4 mmHg) however, when losartan (antagonist AT1) was administered in the drinking water, it prevented the development of hypertension, whereas hypertension did not prevent with BMY 7378 (antagonist 1D-ARs). At the functional level, phenylephrine-induced contraction in aorta was greater (4.2 ± 0.3 g maximal effect) in Ang II-treated rats than in controls (2.7 ± 0.4 g), this increase only was observed in aorta but not in caudal artery; furthermore, BMY 7378 and losartan inhibited the hyperreactivity produced by Ang II in aorta. Similar events were observed through histology of the vessels, where only the aorta of rats treated with Ang II developed hypertrophy. The data support our hypothesis that Ang II-induced hypertension and hypertrophy might be mediated indirectly through 1D-adrenoceptors. Acknowledgements: supported by grants 47481, 102022 from CONACYT, IN224408, IN223009 from DGAPA, UNAM and PAPCA, FESI, UNAM 2009-2010 (Grant 35 to MIB) EFFECT OF UNCARIA TOMENTOSA IN BREAST CANCER INDUCED BY 7,12DIMETHYLBENZ[A]ANTHRACENE. Manuel de Jesús Gallegos-Saucedo*, Patricia Yahuaca-Mendoza, Rosalinda Gutiérrez-Hernández y José Luis Alvarado-Acosta. Programa de Doctorado en Farmacología, U.A. de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, México. E-mail: [email protected] Undoubtedly, some antineoplastic drugs have been derived from plants, being an important phytotherapy source. One of them, empirical and scientific, is Uncaria tomentosa (UT). In the present study evaluated the utility of the aqueous extract of the bark of Ut in breast cancer model induced by 7,12-dimethylbenz[a]anthracene (DMBA). Sprague Dawley female rats of 50 days, were divided into 4 groups (n= 15 per group): 1) control vehicle (safflower oil); groups 2 and 3 received DMBA 10 mg/kg, intragastrically for 6 weeks (monday to friday) to induce breast cancer (CADMBA). In addition, group 2 received co-administration with Ut (160 mg/kg) as preventive therapy. In group 3, once the tumors were present, were given similar doses of Ut (6 weeks) to assess reversal of the process.Control Ut group was included. Lipoperoxidation (LPox), stability of erythrocyte membranes (EPME) and tumor markers carcinoembryonic antigen (CEA), alphafetoprotein (AFP) and acid phosphatase (AP), was measured; also breast tissue for histological evaluation. Our results showed that Ut reduced LPox increased in CA DMBA, and recovered the EPME reduced, both in prevention and reversal models; levels of CEA, AFP and AP increased at 175%, 400% and 14% over the control, respectively, showed partial recovery with Ut administration. Pathological diagnosis showed variable response in number and distribution of mammary tumors, with survival of 40% without treatment. Histologically was observed large cell tumors with atypical lymphocyte infiltration and diffuse growth pattern. Alterations were modulated by administering Ut, because the breast architecture was observed most conserved and survival increased to around 85%. Our results support the therapeutic value of Uncaria tomentosa in experimental breast cancer. * Number 15608 CONACYT Project Fellow. Project funded by SEPPIFI 2008-2009 and Fondo Sectorial SEP-CONACYT, Ciencia Básica, CB-2008-0-105986. 100 EARLY OBESITY POTENTIATES DEVELOPMENT OF RENAL FAILURE: ROLE OF 1 NITRIC OXIDE PATHWAY AND OXIDATIVE STRESS Ana Gámez-Méndez , Hilda Vargas1 2 3 3* 1 Robles , Mónica Arellano-Mendoza , Amelia Ríos , Bruno Escalante CINVESTAV I.P.N. 2 Departamento de Biomedicina Molecular, México D.F., Escuela Superior de Medicina I.P.N., 3 México D.F. CINVESTAV MONTERREY, Apodaca, N.L. Obesity is a serious problem across the world linked to several pathologies and recently has been considered as a risk factor in the development of renal failure. We studied whether mild obesity contributes to progression of the disease and tested the effects of an antioxidant and L-arginine treatment (Tx) on nitric oxide (NO) metabolism and kidney failure parameters in mice with chronic kidney failure (CKD) during mild obesity. WTC57 mice were fed with a highfat diet (HFD) or a normal diet (ND) for up 2 weeks and subjected to either sham surgery or 5/6 nephrectomy (Np). Mice were divided in 5 groups: ND/sham, ND/Np, HFD/sham, HFD/Np and HFD/Np + Tx. Treatment consisted in Vitamin C (83 mg/Kg weight), Vitamin E (46 mg/Kg weight) and L-arginine (200 mg/Kg weight). In ND mice, 5/6 nephrectomy increased urinary volume from 1.15± 0.1 to 3.14 ± 0.1 mL/24h; proteinuria from 2.7±0.2 to 3.3 ± 0.1 mg/24h; •– 5 blood pressure from 84 ± 4 to 117± 2 mmHg; renal O2 production (DHE dye) from 7.8x10 to 5 9.5x10 fluorescence arbitrary units; eNOS mRNA expression halved; plasma tetrahydrobiopterin concentration (capillary electrophoresis) decreased from 23.7 ± 3 to 14.2 ± 2 pmol/mL; urinary NO2 (Griess reaction) decreased from 370 ± 82 to 142 ± 36 µM. In HFD/Np mice all those parameters worsened. Finally, treatment ameliorated renal damage and statistically improved NO metabolism in HFD/NFX + Tx mice. We conclude that mild obesity worsens renal damage during CKD through reduction in expression and activity of eNOS. EFFECT OF CHRONIC RESTRAINT STRESS ON 5-HT7 RECEPTOR EXPRESSION IN RAT ADRENAL GLANDS. García-Iglesias BB, Terrón JA. Departamento de Farmacología, CINVESTAV-IPN, Apdo. Postal 14-740, Zacatenco 07000, México D.F. It has been shown that serotonin (5-hydroxytryptamine; 5-HT), produced by chromaffin and mast cells, acts as a paracrine factor stimulating the activity of adrenocortical cells (1). In rats, the stimulatory effect of 5-HT on the adrenal cortex has been widely documented (2) and it has been recently demonstrated that the corticotropic effect of 5-HT on rat glomerulosa cells is mediated through 5-HT7 receptors (3). The adrenal gland, on the other hand, is activated by repeated restraint stress (4) but the possible changes of adrenal 5-HT receptors and their function under chronic stress conditions remain largely unknown. This study was designed therefore to evaluate the effect of chronic restraint stress (CRS; 20 min/day for 2 weeks) on 5-HT7 receptor immunoreactivity and protein expression in the rat adrenal gland; control rats were maintained undisturbed in their home cages. One day after the end of the CRS treatment, adrenal glands from control and experimental animals were processed for immunohistochemistry and western-blot assays using specific antibodies. Immunoreactivity to the 5-HT7 receptor was found in the cortex in the form of clusters through the zona fasciculata, and in the medulla. Exposure to CRS induced an increase of cortical 5-HT7 receptor immunoreactivity which appeared more widely spread throughout the zona fasciculata; immunoreactivity in the medulla was apparently unchanged but this needs confirmation. The amount of 5-HT7 receptor protein measured in whole adrenals significantly increased in chronically restrained animals. Results suggest that the 5-HT7 receptor could play an important role in adrenal glucocorticoid secretion under chronic stress conditions. 101 MDR1 EXON 12 GENE POLYMORPHISM IN RENAL TRANSPLANT DONORS AND ITS RELATIONSHIP TO TRANSPLANT OUTCOME Garcia-Roca P, Rodriguez-Espino B, Hernández AM, Ortiz L, Medeiros M. Laboratorio de Investigación en Nefrologia, Hospital Infantil de México. México DF. P-glycoprotein (MDR1) is a multidrug efflux protein that extrude tacrolimus from the cell, it is present in renal tubular cells. Tacrolimus is related to the development of chronic allograft nephropathy. The aim of the study was to determine if the MDR1 Exon 12 gene polymorphism in the transplant donor influence the development of chronic nephropathy, tacrolimus levels, tacrolimus dose requirements and glomerular filtration rate in the transplant recipient. DNA sample was obtained in 29 living related renal transplant donors. The MDR1 Exon 12 genotyping was performed by direct sequencing. The information regarding the evolution of the transplant recipient during the first 12 months was obtained from the clinical chart, including: number of acute rejection episodes, presence of biopsy proven allograft nephropathy, tacrolimus blood levels and dose requirements at 1, 6 and 12 months post-transplant. Glomerular filtration rate was estimated using Schwartz formula, the delta of glomerular filtration rate at 12 months was evaluated in all patients. All the patients had at least one protocol biopsy performed at six months post-renal transplant. Four donors were C/C (13.7%), thirteen were C/T (44.8%) and twelve were T/T genotype(41.3%). 21 patients had chronic allograft nephropathy (75% in C/C donors, 69% in C/T donors, and 75% in T/T donors, p>0.05), six patients had biopsy proven acute rejection during the first 12 months post-renal transplant (25% in C/C donors, 30.7% in C/T donors and 16.6% in T/T donors, p>0.05). No difference was found in tacrolimus blood levels, tacrolimus dose requirements at 1, 6 and 12 months by genotype.The delta of glomerular filtration rate at 12 months was similar in all genotypes. Chronic allograft nephropathy and acute rejection episodes were not influenced by the MDR1 Exon 12 genotype in the donor THE ENANTIOMERS +(-)CATECHIN AND –(-)EPICATECHIN INDUCE APOPTOSIS AND MODULATE GENES METHYLATION IN BREAST CANCER CELLS LINES. José Rubén García Sánchez*, Melissa Hernández Martínez*, Guillermo Manuel Ceballos Reyes*, Martha & Patricia Sierra Vargas , Ivonne María Olivares Corichi*. *Postgraduate Studies and Research Section, School of Medicine National Polytechnique Institute, Plan de San Luis y Diaz Miron, & Casco de Santo Tomas, 11340 Mexico Distrito Federal, Mexico. Department of Biochemistry and Environmental Medicine, National Institute ofRespiratory Diseases ―Ismael Cosio Villegas‖, Calzada de Tlalpan 4502, Sección XVI, 14080 México Distrito Federal, Mexico. Dietary and nutritional factors have been reported to have gene expression and genome modulating effects in the development or prevention of certain cancers. In fact, some studies suggest that a diet rich in flavanol, may be associated with a decreased risk of breast and other cancers. Whether well, +(-)Catechin and +(-)epicatechin, are the most common flavanols in foods and they are the main portion in the plasma after the consumption of rich foods in flavanols, few studies have been performed about of their antineoplasic proprieties. In the present study, we investigated the antineoplasic activity of two enantiomeric forms +()Catechin and +(-)epicatechin in breast cancer cells lines. MCF-7, MDA-MB-231 and BT-474 breast cancer cells lines were grown in the presence of +(-)catechin, -(-)epicatechin and the effects on the cell viability and modulation of tumor suppressor gene methylation (DAPK1 and APC) were analyzed. The obtained results showed that flavanols inhibited cell proliferation of MDA-MB-231 and MCF-7. Interestingly, the inhibitory effect on BT-474 cell line was observed when a mix the flavanols was used. Whether well,+(-)catechin and –()epicatechin presented the same fifty inhibitory concentration (IC50 = 350 µM), cell growth inhibition was observed at different days after exposure. In addition, we provide new evidence using methylation specific PCR (MSP) that +(-)catechin and –(-)epicatechin, can alter genes methylation in breast cancer cells lines, and that this change is coordinated with an apoptosis induction in these cell lines. 102 STRIATAL PROTECTION IN NNOS KNOCK-OUT MICE AFTER QUIN-INDUCED OXIDATIVE DAMAGE: RELATIONSHIP WITH HUNTINGTIN EXPRESSION Gerónimoa b a a a Olvera C ., Heras-Romero Y ., Tristán-López L ., Osorio-Cruz Y ., González-Esquivel D ., a a a Ríos C , Pérez-Severiano F . Departamento de Neuroquímica. Instituto Nacional Neurología. ―Manuel Velasco Suárez‖. Insurgentes Sur # 3877, Col. La Fama, 14269, b Tlalpan, México D.F., México. Departamento de Bioterio. Instituto Nacional de Neurología. ―Manuel Velasco Suárez‖. Insurgentes Sur # 3877, Col. La Fama, 14269, Tlalpan, México . D.F., México Nitric oxide (NO) is a mediator of oxidative cellular damage. There are evidences about the participation of neuronal nitric oxide synthase (nNOS) in the mechanism of neurodegeneration in Huntington’s disease (HD). HD is caused by an expanded polyglutamine (polyQ) tract in the protein huntingtin (htt). The activation of NMDAr by its agonist quinolinic acid (QUIN) evokes an increase of nNOS function and promotes the oxidative stress. The aim of the present work was to study the participation of nNOS in QUIN-induced oxidative stress as well as to dilucidate its relationship with the htt expression in nNOS knock-out mice. To reach this goal, we bred a colony of the B6129-NOS1tm1P1h line of nNOS knock-out mice. Three genotypes were determined by PCR: wild type (+/+), heterocigotes (+/-) and knock-out (-/-). Saline solution (SS) or QUIN was microinjected in striata of each mouse and circling behavior (CB), GABA levels, oxidative stress, NOS activity and expression were measured. Results showed that CB was reduced and GABA depletion was significantly attenuated in nNOS knock-out mice; this group also showed significant protection (p<0.05) in the striatum against oxidative damage induced by QUIN, in comparison to wild type and heterocigotes mice. In contrast, the expression of the mRNA of htt was increased in all animals treated with QUIN compared with the animals microinjected with SS (p<0.05). This results demonstrate that NO is involved in oxidative damage and neurodegeneration process induced by QUIN. Additionally we found that the htt increase during the acute response to QUIN challenge may provide a partial explanation for degeneration observed in HD. PHARMACOEPIDEMIOLOGICAL STUDY ABOUT THE USE OF METHYLPHENIDATE IN A GROUP OF PATIENTS WITH ATTENTION – DEFICIT AND HYPERACTIVITY 1 1 2 DISORDER Gómez Galicia Diana L , Rodríguez Fragoso Lourdes , López Aymes Gabriela , 3 1 1 2 Sánchez-Alemán M ., Reyes Esparza Jorge Facultad de Farmacia, Facultad de 3 Comunicación Humana, UAEM, INSP, Morelos, México. Attention-Deficit and Hyperactivity Disorder (ADHD) is one of the most commonly diagnosed childhood disorder. According to DSM-IV the global prevalence in scholarship children is between 3 to 5%; in Mexico the estimated prevalence is 5%. Treatment is based on stimulant drugs, specifically methylphenidate (MPH). Several questions exist relating to its diagnosis, treatment, and long-term effect on ADHD child development. Consequently, research is warranted to accurately describe prescribing use of stimulants. Objective: to evaluate the use of stimulants in a group of Mexican children with ADHD in order to know some pharmacoepidemiological data. Methods: An observational and descriptive study in pediatrics patients based on a survey in a one year period (June 2009 to June 2010) was done. Survey was answered by children parents who signed an informed consent. Patients with diagnosis of ADHD and ADD received stimulant treatment with and without co-morbidity and those in evaluation were consider. Results: Of 124 surveys, 57 were selected according to inclusion criteria. 82% of patients received methylphenidate and 18% non-stimulant treatment. The mean age of stimulant users was 7.94 years (4-13 years), 82.4% were male, 80% were in a primary school and 94% had a nonpharmacologic treatment. Immediate release was the most prescribed form in three different commercial presentations, and 8% received the long term release. We found that children with seven years old were who received more methylphenidate prescription. The age and having a comorbidity increased the probability (p<0.005) for receiving methylphenidate treatment. The most frequent side effect reported was loss of appetite. Conclusion: Methylphenidate in an immediate action form was the most prescribed stimulant drug in seven years old children with ADHD in the population studied. High percentage of children received methylphenidate treatment . 103 ESSAYS OF BIOLOGICAL ACTIVITY AND SECONDARY METABOLITES SEARCH OF 1 2 JUSTICIA SPICIGERA Juan Carlos Gomez Verjan , Maria Isabel Aguilar Laurents , Ricardo 3 4 1 Reyes Chilpa , Gil Alfonso Magos Guerrero Posgrado Ciencias Biológicas, Facultad de 2 3 Ciencias, UNAM, Departamento de Farmacia, Facultad de Quimica,UNAM, Departamento de Farmacología, Facultad de Medicina, UNAM The present describes the project done around Justicia spicigera known in Traditional Medicine of Mexico as ―Muitle‖. The data obtained from the ethnobotanical information indicated, that for medicinal preparations used aerial parts mainly shaped like infusion recommended for dysentery, infections of the skin and kidneys, as well as anemia. Given the medicinal uses of J. spicigera against dysentery we performed a monitoring antimicrobial, antiparasitic and spasmolytic test as well as a test against yeasts and molds according to their use against infections of the skin and kidneys. We found no significant activity in the case of antimicrobial monitoring nor spasmolytic tests but parasite monitoring activity was observed against all parasites tested. As safety test we performed the following tests: Artemia salina which indicated a LC50 of 100 μg/mL for infusion and harmless for extracts and the acute toxicity test in CD-1 mice by i.p. and oral ways for the methanol extract and the infusion. The infusion showed a LD50 of 63.3 mg/kg i.p., and >5g/kg orally. In the case of i.p. results for both extracts, were supplemented by histopathological analysis. Scientific literature on this species, reported that the genus Justicia is rich in antiviral and cytotoxic molecules, so a study of reverse transcriptase inhibition of HIV-1 was carried out, and a trial against six tumor cell lines.As chemical analysis, it was carried out a profile of groups of secondary metabolites which showed the presence of carbohydrates, amino acids and polyphenols at high concentrations. From one of the fractions vanillinic acid was isolated. ASSESSMENT OF APOPTOSIS OF MONONUCLEAR CELLS INCUBATED WITH CAMPTOTHECIN, COMPARASION OF THREE METHODS Gómez-Montalvo A, GarcíaArenas G, Meza R, Goytia-Acevedo RC. Facultad de Medicina, Universidad Juárez del Estado de Durango, Gómez Palacio, Durango. Detection of apoptosis may be useful to understand the mechanism of drug action, mechanisms associated with the nature of disease and the effectiveness of treatments, among others. It is considered that the determination of morphological changes, changes in the symmetry of the cell membrane, DNA degradation, and activation of caspases, are the more sensitive tests for detection of apoptosis. The purpose of this study was to show an analysis of the results obtained from mononuclear cells incubated with the apoptosis inducer, camptothecin, after evaluation by morphological changes, and the methods of Tunel and Annexin V. Mononuclear cells were isolated from peripheral blood of 3 healthy volunteers. The cells were incubated with camptothecin for 1.5, 3 and 4 hours and processed by the three methods for analysis by flow cytometry. The results show a graphical analysis of apoptosis for each method. The incubation with camptothecin led to 40% of apoptosis in the cells after four hours of incubation. With the Tunel method was obtained less dispersion of data, however up to 4 hours of incubation, the percentages obtained by the three methods were similar in each time. Evaluation of apoptosis by the methods studied and up to 4 hours of incubation with camptothecin, allows analysis of apoptosis of mononuclear cells in a similar manner, although that the methods used measured events at different stages of apoptosis. 104 ANIMAL MODEL OF MYOCARDIAL FIBROSIS IN THE SETTING OF CHRONIC CARDIOVASCULAR COMPLICATION OF TYPE 2 DIABETES MELLITUS Guadrón Llanos AM, Leal Anguiano AI, Huerta Olvera SG; Vázquez AO, Miranda Díaz AG, Salazar Montes A; Gálvez Gastelum FJ; Rincón Sánchez AR; Islas Carbajal MC Universidad de Guadalajara Centro Universitario de Ciencias de la salud. The aim of the study was to assess changes in the myocardium in an animal model of type 2 diabetes in order to resemble as much as possible the events that occur in type 2 diabetic patients and that may be useful for chronic studies. Methods: Hyperglycemia was induced in male Wistar rats (150-200 g) by 5 intraperitoneal injections of low doses of streptozotocin (20 mg/kg) in addition to a high fat diet. The evaluation was done by metabolic, blood glucose measures and cardiac histological studies. They were sacrificed at different times until 25 week to evaluate the progression of cardiac fibrosis and the stable hyperglycemia. Results: Experimental diabetes using streptozotocin in addition to a high fat diet caused stable hyperglycemia, without their gradual recovery to normoglycemia. The use of insulin therapy to sustain life was not necessary suggesting that doses calculated to cause a partial destruction of β cell mass in addition to a high fat diet was appropriated. Besides, we observed a gradual development of interstitial fibrosis, getting started at week 15 after induction, becoming very obvious at week 25. We found similarities with the human condition in our model, which presented moderate obesity, polydipsia, polyphagia, polyuria, and stable hyperglycemia without a tendency to cause ketosis or deterioration into type 1 diabetes mellitus. Conclusion: This model could be useful to investigate mechanisms related to this important chronic macrovascular complication of diabetes and useful to research in order to find new therapies. PARTICIPATION OF ANGIOGENIC FACTORS IN THE MORPHOLOGY OF LEIOMYOMA 1 DERIVED FROM HUMAN UTERUS Guerrero Zepeda María Alejandra , Becerril Montes 2 2 1 Adriana , Cárdenas Jaramillo Luz María , Ocharán Hernández María Esther , Mota Morales 1 1 Alicia, Calzada Mendoza Claudia Camelia . [email protected] Laboratorio de Señalización Intracelular, SEPI-Escuela Superior de Medicina-IPN, Plan de Sn Luis y Díaz 2 Mirón Sn, México D.F. Laboratorio de Histología, SEPI-Escuela Superior de Medicina-IPN, Plan de Sn Luis y Díaz Mirón Sn, México D. F. Uterine leiomyomas are the most common of the benign pelvic neoplasm. The function of the progesterone and estrogen in leiomyomas as etiological agents has been demonstrated; through its paracrine and autocrine effects, which stimulate the production of several factors such as oxide nitric, and endothelin, which are able to regulate mitosis, extracellular matrix (ECM) turnover and angiogenesis. Uterine leiomyomas presents excess ECM which to act as a source growth factors, cytokines, angiogenic and inflammatory response mediators, produced by tumoral cells, those events are associated with growth and differentiation cell, which are critical to leiomyoma growth. In this study, we analyzed the relationship between histological morphology of leiomyoma and expression proteic of ERα and PR-A-B, endothelin converting enzyme and endothelial nitric oxide synthase in different phases of the menstrual cycle. Samples of myometrium, subtumoral tissue and leiomyoma were obtained from women with diagnoses of uterine myomatosis of medium elements and analyzed by immunoblotting to identify ERα, PR-A-B, ECE and eNOS; the bands were revealed by chemiluminiscence, the densytograms were measurement with Quantity One software. Another portion of the samples were stained for histological analysis with H-E and Gomori Trichromic. The morphological characteristics (cell density and ECM) were observed. We founded that in proliferative phase are increased the proteins of ERα and eNos, while in secretory phase, was predominant the isoform A of PR, together with ERα and ECE expression. The hyaline leiomyomas predominates in proliferative phase, characterized for more content ECM, while in secretory phase predominates cellulars type, in this morphology we found higher cell density, and the size miocito is smallest whit respect the quantity of blood vases, the cellular myomas contents are more irrigated. In conclusion, the ECE expression is stimulated by PR-A and ERα during secretory phase, probably regulating the differentiation of the cellulars leiomyomas whit higher the density of blood vessels. ERα can stimulate the synthesis of the eNOS in proliferative phase, promoting the differentiation to hyaline leiomyomas. 105 RESINIFERATOXIN INHIBIT PRO-INFLAMMATORY CYTOKINES AND NITRIC OXIDE IN MODEL OF LIPOPOLYSACCHARIDE-INDUCED INFLAMMATION O. Gutiérrez1 1 1 1 Coronado ,J.L. Muños Carrillo , M.S Luevanos Raymundo , M.L. Miranda-Beltran , P.T. 1 1 Villalobos-Gutierrez [email protected] Centro Universitario de los Lagos; Universidad de Guadalajara Pro-inflammatory cytokines, TNF-α and IL-1β, play pivotal role in the pathogenesis of autoimmune and inflammatory disorders. Inhibition of their action may provide therapeutic benefits in several diseases. Different chemical structural types of natural products exhibit anti-inflammatory activity and are considered to be potential drug candidates against the inflammation-related pathological processes. The resiniferatoxin a naturally occurring diterpene containing a homovanillic acid ester, showed pharmacological effect including antiinflammatory activity. BALB/c mice were exposed to LPS application (250µg/100g) in order to evaluate the anti-inflammatory activity resiniferatoxin. Five different groups were used: (i) control group (none stimulus); (ii) LPS; (iii) LPS-dexamethasone; (iv) LPS- resiniferatoxin (20 µg/kg) and (v) vehicle control. Plasmas samples were collected and stored at -70ºC, 180 min after the last LPS or treatment administration. The resiniferatoxin after peripheral administration reduced the nitric oxide levels significantly p<0.001. As well as the releasing TNF-α was significantly inhibited (p<0.005). These findings suggest that the anti-inflammatory action of resiniferatoxin is mediated by pro-inflammatory cytokines and nitric oxide inhibition and may be promising drug for targeted inhibition inflammatory diseases and this effect may be related to the inhibition of inflammatory response via NF-κB. COMPARATIVE STUDY OF ANTIOXIDANTS IN THE PREVENTION OF ACUTE HEPATOTOXICITY INDUCED BY CARBON TETRACHLORIDE IN MURINE MODEL. Rosalinda Gutiérrez-Hernández, José Luis Alvarado-Acosta, Sonia Sifuentes-Franco, José Luis Martínez-Rodríguez y Patricia Yahuaca-Mendoza. Programa de Doctorado en Farmacología, U.A. de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, México. E-mail: [email protected] and [email protected] Extracts of the plant Rosmarinus officinalis, L. (Rosemary) have been studied in several experimental models to establish scientific basis about its hepatoprotective and antioxidative (AOx) properties. Also has been used as a home remedy. In order to know its efficacy and in vivo potency, we studied the comparative effect of R. officinalis, against other AOx, which are in commercial and clinical use (in all treatments the administered dose was 10 mg/kg): butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), E vitamin, Ascorbic acid (ASCA) and Citric acid (CITA) in murine model of acute hepatotoxicity induced by carbon tetrachloride (CCl4) in male Wistar rat at a single dose of 4 g/kg of body weight, oral route, dissolved in corn oil. R. officinalis was prepared in our laboratory as a methanolic total extract, after maceration, distillated by reflux, bleached and concentrated by rotary evaporator. Liver lipoperoxidation degree was evaluated measuring malondialdehyde (MDA); liver damage was assessed by measurement of glycogen deposition and activity of serum alanine aminotransferase (ALT). Our results showed that oxidative damage from CCl4, 24 h post-administration, increased the MDA (357%). R. officinalis significantly prevented this oxidation maintaining MDA levels below control. E Vitamin, BHA and ASCA had good effect but less potent than R. officinalis (49%, 71% and 72% over the control, respectively); with lower potency CITA (91%) and with practically no hepatic effect was BHT (202% over the control). Both the severe decrease in liver glycogen and increased ALT induced by CCl 4, were prevented with R. officinalis as a promising antioxidant and hepatoprotective agent in acute model of hepatotoxicity. Project funded by Fondo Sectorial SEP-CONACYT, Ciencia Básica, Code CB-2008-01-105986. 106 CRITERIA ON WHICH PROFESSORS AND STUDENTS OF ODONTOLOGY FACULTY FROM UNAM BASED THEIR DRUG PRESCRIPTION R. GUZMÁN ÁLVAREZ, M. 1 1 2 MEDEIROS DOMINGO , A.E. CAMPOS SEPÚLVEDA . L.I. REYES LAGUNES Odontology 1 2 Faculty Pharmacology Department, Medicine Faculty, Psicology Faculty, (UNAM); Mexico, City., 04510. The purpose of the study is to identify the cases where drugs are prescribed by professors and students of the Odontology faculty of UNAM, which are the pharmacology groups more used, the once they prefer and to verify if they follows the good prescription guide from the WHO. An eight question survey was made to 16 professors and 65 students of fourth grade career. The most used NSAID’S are: Ibuprofen, Naproxen, Ketorolac, Acetaminophen; the antibiotics more used are: Ampicillin, Amoxicillin, Clindamycin, Penicillin V; the most common mistakes are: to unknown the dosage, the prescription, presentations, to get confuse on the pharmacological effects; and last when the students prescribe, they support in the clinical professor, their classmates or a medical representative from a laboratory. Therefore, I conclude that it is necessary to use this information in order to improve the educations by making some guides including the guide from the WHO within the curriculum having refresher trainings among others. LINALOL THE ANTIDEPRESSANT PRINCIPLE OF Litsea glaucescens (Mexican Bay) ESSENTIAL OIL Guzmán-Gutiérrez S. L.ª, Gómez-Cansino R.ª, Pérez-Flores, F. J.ª, b García-Zebadúa J.C.ª, Jiménez-Pérez, N. , Reyes-Chilpa Rª*. ªInstituto de Química, UNAM. b *[email protected]. Instituto de Ecología A.C., Xalapa, Ver. Francisco Hernandez in his ―Historia de las Plantas de la Nueva España‖ (1571-1577) described a plant named in Nahuatl language ―Ecapatli‖, as following: ―It is a kind of ―laurel‖ minor than ours, and with smaller leaves, but similar in whatever else. The natives cure paralysis with its odorous smoke, its decoction administered in washing and baths heals fatigue and epilepsy of children‖. ―Ecapatli‖ has been interpreted as Litsea glaucescens (Lauraceae) commonly named ―laurel‖. Besides its culinary uses, L. glaucescens infusion has been used to treat anger, sadness, nervousness, among others illness. Based on above, the neuropharmacological profile of the essential oil of L. glaucescens was evaluated in mice using several experimental models: Forced swimming test (FST: antidepressant activity), open field test (OFT: spontaneous locomotor activity), rotarod (motor coordination), traction performance (myo-relaxant effect), elevated plus-maze (anxiolytic activity) and exploratory cylinder (sedative activity). The essential oil induced a reduction of immobility at 100 mg/Kg in the FST, but did not modify the spontaneous locomotor activity in OFT. The essential oil at the same dose did not have effect on motor coordination, neither showed myo-relaxant, anxiolytic or sedative properties. The composition of essential oil was analyzed by GC/MS, identification of compounds was based on comparison of retention times and mass spectra of authentic standards, and with NIST 05 mass spectra library. The linalool, one of its major constituents presented antidepressant activity in FST at 100 mg/Kg, with a slight depression on the spontaneous locomotor activity in OFT, but, without modifying motor coordination or muscle strength. These data reveal that the essential oil of L. glaucescens possess antidepressant effect in mice, providing support for its use in Mexican Traditional Medicine 107 EXPERIMENTAL ASSESSMENT OF ANTIINFLAMMATORY EFFECT OF Hamelia patens 1 2 2 Jacq. AND Calea urticifolia Mill (DC). Guzmán, P ; García-Chávez, E. ; Soto-Peña, G. ; 2 Juárez, B. 1. Programa Multidisciplinario de Posgrado en Ciencias Ambientales, Universidad Autónoma de San Luis Potosí. Universidad de Guanajuato, División de Ciencias Naturales y Exactas, Campus Guanajuato, México. 2. Instituto de Investigación de Zonas Desérticas, Universidad Autónoma de San Luis Potosí, México. Contact: [email protected]. Callejón del Meco 5. Zona Centro. Guanajuato, Gto. México. Telephone number: (473) 73 26272. The present investigation evaluated the inhibitory effect of ethanol extract from Hamelia patens and Calea urticifolia on the secretion of pro inflammatory cytokines in Wistar rats serum through ELISA immunoassay. The results showed that the plants extracts have inhibitory effect on TNF-, IL-1 and IL-6 at different doses. Wistar male rats were treated independently with these ethanol extracts: Calea urticifolia at dose 0.044mg/kg; Hamelia patens at dose 0.403mg/kg (those being the traditional indigenous doses); Calea urticifolia at dose 0.088mg/kg; and Hamelia patens at dose 0.806mg/kg (those being twice de traditional doses); and Meloxicam at 0.1 mg/ kg dose (prototype drug);. Treatments were given intraperitoneally, 1hr before inducing local inflammation with carrageenan at 1%, according to Arredondo, 2008 [1]. Blood samples were obtained by cardiac puncture at 4.5hr of experiment, when the volume of inflammation of plantar fascia of the animals was maximum. ELISA immunoassay was used to evaluate the concentration of TNF-, IL-1 and IL-6 cytokines in serum. The plants extracts have inhibitory effect on TNF-, IL-1 and IL-6, being the dose of 0.044 mg/kg from C. urticifolia extract the most effective for TNF- inhibition. Only the extract from H. Patens showed the best inhibitory effect for IL-6, at dose of 0.806 mg /kg comparable to the prototype drug. The traditional indigenous use of these plants was verified, being the C. urticifolia extract the most effective one, and also the one with the lower dose and greater effect. (Project supported under PROMEP Folio UASLP-PTC- 151 and FAI under the agreement number C08-FAI-10-37.73). EFFECT OF ETHANOL EXTRACT FROM Calea urticifolia (Mill.) DC. ON THE 1 REGULATION OF INFLAMMATION MEDIATED BY ADIPONECTIN. Guzmán, P. ; Soto2 2, 2 Peña G. ; Cárdenas, N. ; García-Chávez, E . 1. Programa Multidisciplinario de Posgrado en Ciencias Ambientales, Universidad Autónoma de San Luis Potosí. Universidad de Guanajuato, División de Ciencias Naturales y Exactas, Campus Guanajuato, México. 2. Instituto de Investigación de Zonas Desérticas, Universidad Autónoma de San Luis Potosí, México. Contact: [email protected]. Callejón del Meco 5. Zona Centro. Guanajuato, Gto. México. Telephone number: (473) 73 26272. The objective of this work was to evaluate the anti-inflammatory effect of the ethanol extract from Calea urticifolia over the systemic inflammation that the adipose tissue generates in the body, and the secretion of adiponectin. Male Wistar rats were used, given a high fat diet and treated with C. urticifolia extract at dose 0.088mg/kg. The results showed that the group treated with plant extract and high fat diet had lower levels of pro inflammatory cytokines and higher levels of adiponectin than the control group. Obesity is a condition that leads to serious health problems. Adipose tissue secretes multiple metabolically proteins called adipocytokines. Adiponectin interacts with insulin signaling in the context of low-grade inflammation, associated with obesity, encouraging the uptake of insulin, and preventing the development of type II diabetes. Two groups of male Wistar rats were fed a high fat diet; one of these groups was given daily 0.088mg/kg of C. urticifolia extract orally; and the other group was treated with water. Blood samples were taken at the end of experiment to evaluate pro inflammatory cytokines and adiponectin serum levels. All parameters were determined by ELISA immunoassay. The groups treated with plant extract showed lower levels of serum glucose and triglycerides than the water groups. The high fat diet/extract group showed decreased levels of TNF- and IL-6. There was an increase in the secretion of adiponectin levels showed in the high fat diet groups, specially the group treated with the plant extract. The oral administration of ethanol extract from Calea urticifolia regulates the secretion of pro inflammatory cytokines and increases secretion of adiponectin when fed a high fat diet. 108 HYPOTHYROIDISM PROTECTS AGAINST ANILINE CAUSED-SPLEEN DAMAGE AND OXIDATIVE STRESS. Hernández-Alvarado J., Rodríguez-Sánchez, R., Ortiz-Butrón, R., Blas-Valdivia, V., and Cano-Europa, E. Laboratorio de Neurobiología. Departamento de Fisiología de la Escuela Nacional de Ciencias Biológicas. IPN. México, DF. [email protected] Aniline is an aromatic amine, widely used in chemical and pharmaceutical industry. Aniline exposure causes selective toxicity in the spleen like fibrosis, splenomegaly, elevated erythropoietic activity, hyperpigmentation, hyperplasia, increased reactive oxygen species (ROS) and other free radicals that initiate events such as lipid peroxidation, oxidation of proteins and DNA. On the other hand, we know that hypothyroidism decreases the basal metabolic state by providing protection against oxidative stress-generating events. So, to determine whether hypothyroidism protects against oxidative stress and cell damage in the spleen caused by intoxication with aniline we used 24 male Wistar rats weighing 240 to 260 g divided into four groups: 1) euthyroid, 2) euthyroid + aniline, 3) hypothyroid, and 4) hypothyroid + aniline. The hypothyroidism was produced by thyroidectomy with reimplantation of the parathyroid gland. Two weeks after surgery, the animals were intoxicated with 1 mmol/kg/d ig aniline for five days. On the fifth day, the animals were sacrificed and the spleen was obtained. One section was processed by the conventional technique of paraffin embedding, while another section of the spleen was used to assess lipid peroxidation, the quantification of reactive oxygen species, reduced glutathione and oxidized glutathione. Our results demonstrated that hypothyroidism prevents the enhancement of oxidative markers as well as the severity of splenic injury caused by aniline intoxication. Funded by grants from the SIP-IPN 20110336. SPERM MORPHOLOGY OF MICE PRENATALLY EXPOSED TO DIAZEPAM Luis Alfredo Ignacio Hernández-Álvarez*, Arturo Martínez-Vargas, Amalia Márquez-Orozco, María Cristina Márquez-Orozco MC. Embryology Department. Facultad de Medicina, Universidad Nacional Autónoma de México. México D.F. 04510. [email protected] Studies performed in our laboratory have shown histological alterations in ovary and testes of mice exposed to diazepam (DZ) in the uterus. In this work we assessed the effect of these alterations upon sperm structure of mice prenatally treated with DZ. One group of dams (E) was sc treated with diazepam (2.7 mg/k/d) from the 6th to 17th day of gestation and another group received saline sol. (C). Their offspring were left to develop until the 6th month of age, when a punction was performed to obtain 10 µl from the tail of epididymis. The aspirate was processed by the Talbot-Chacon modified method for micro volumes and assessed with photonic microscope. The number of sperms, sperm viability, and the presence of acrosomal reaction and proportion of abnormal forms were determined in each preparation. Aspirates from E animals showed a greater amount of living sperms with acrosomal reaction (p<0.05). These results suggest that the drug modifies the biochemical integrity of sperm membranes. 109 DIMORPHISM IN SEXUAL BEHAVIOR OF CD-1 MICE PRENATALLY TREATED WITH DIAZEPAM Luis Alfredo Ignacio Hernández-Álvarez*, Amalia Márquez-Orozco, María Cristina Márquez-Orozco. Embryology Department. Facultad de Medicina, Universidad Nacional Autónoma de México. México D.F. 04510. Email: [email protected] The aim of this work was to compare the expression of sexual behavior of female and males mice prenatally treated with diazepam (DZ). A group of CD-1 strain female mice maintained in stock environmental conditions with 12/12 light-dark cycles was submitted to daily single doses of 2.7 mg/kg/bw/sc of DZ from day 6th to 17th of gestation. A control group (C) received saline solution. The youngsters were born and continued their normal development until the 6th month, male offspring sexual activity was tested with receptive ovariectomized females in which the estrus phase was induced with ethynylestradiol. The spontaneous female offspring sexual activity to non-treated experienced males of the same age was tested. In both cases they were documented in sessions of 3 trials, one per week, in 2 occasions: at 6 and 20 month of age. Trials were performed during the dark phase of the light-dark cycle for lapses of 30 min under infrared illumination and were videorecorded. Precopulating and intercourse behaviors were assessed. Prenatally administered DZ seems not to interfere with sexual interest of males, since no difference was found during the precopulatory phase. During the copulating stage, adult DZ males showed greater incidence of interruptions of intravaginal penetration, while senile DZ males had lower latencies of mount series and greater proportion of ejaculations. Both adult and senile DZ males exhibited a significantly larger incidence of falls and pauses during mount series with intromission. In DZ females precopulating behavior tended to be shorter. In the copulating phase, their lordotic indexes, proportion of lordotic females by trial and intensity of lordosis were significantly greater, as much in adults as in senile mice. Results show a permanent dimorphic effect in the expression of the sexual activity between males and females mice, with facility patterns for females and difficulty for males, which suggests a modification in the consecutive neural interaction due to the prenatal exposure to DZ. PALMITONE PREVENTS PTZ-CUASED OXIDATIVE STRESS AND CELLULAR DAMAGE 1 2 1 IN BRAIN. Hernández-García, A ., González-Trujano M. E ., Cano-Europa, E . 1 2 Departamento de Fisiología, Escuela Nacional de Ciencias Biológicas-IPN. Instituto Nacional de Psiquiatría ―Ramón de la Fuente Muñiz‖. México, D.F. [email protected] Palmitone is a secondary metabolite of polyketide origin. It was extracted from leaves of Annona diversifolia Saff. (Annonaceae). Also, it was observed that palmitone posses an anticonvulsant propierties against penicillin-, 4-AP- as well as neuroprotective effect against PTZ-caused hippocampal damage. Thus, our objective was to evaluate if palmitone protects against PTZ-caused oxidative stress in brain regions as hippocampus, striatum and cerebral cortex. We used 24 Wistar rats dividied in four groups of 6 animals: 1) DMSO + 0.9 % ss, 2) DMSO + 50 mg/kg PTZ, 3) 50 mg/kg palmitone + 0.9 % ss and 4) 50 mg/kg palmitone + 50 mg/kg PTZ. Two days after administration, the animals were sacrificed by decapitation and the hippocampus, striatum and cerebral cortex were dissected. The samples were used to determine lipid peroxidation, quantification of reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized (GSSG) content. It was observed that palmitone prevents the PTZ-caused oxidative stress induced neuronal damage in CA3 hippocampal regionin brain regions. This study was supported by SIP-IPN 20100478 and 20110473. 110 NITRIC OXIDE PROMOTES THE RECOVERY OF COGNITIVE DEFICIT IN AN a EXPERIMENTAL MODEL OF CHOLINERGIC DAMAGE. Hernández-Melesio MA. , b c c e Quevedo-Corona, L. , Jiménez-Capdeville, ME. , Santoyo-Pérez, ME. , Gelista-Herrera N , a d a a González-Esquivel, D. , Sánchez-Mendoza, A. , Ríos, C. , Pérez-Severiano, F. a b Departamento de Neuroquímica. Instituto Nacional de Neurología Departamento de c Fisiología. Escuela Nacional de Ciencias Biológicas, IPN. Departamento de Bioquímica, d Facultad de Medicina. Universidad Autónoma de San Luis Potosí Departamento de e Farmacología. Instituto Nacional de Cardiología ―Ignacio Chávez‖. Departamento de Neuropatología, Instituto Nacional de Neurología y Neurocirugía The relationship between NO and cholinergic system has been evidenced by blocking cognition through the use of inhibitors of the nitric oxide synthase (NOS), while NO donors can facilitate it. The NO donor molsidomine (MOLS) has been used as a pharmacological tool in order to antagonize the cognitive deficit associated to cholinergic hypofunction produced by scopolamine. However, the participation of NO in the recovery of cholinergic deficit due to the administration of the cholinergic immunotoxin, 192-IgG saporin (SAP) has not been analyzed. The aim of the present study was to determine the impact of the MOLS in the recovery of cognitive deficit using the experimental model of cholinergic damage induced by 192 IgG saporin (SAP). For this purpose male Wistar rats were injected with SAP (0.22 µg) or PBS (0.1M pH 7.4) into the medial septum nucleus. After seven days, SAP and PBS groups were divided into isotonic saline solution (SS, i.p.) and MOLS (4 mg/kg i.p.) subgroups. The cholinergic damage induced by the immunotoxin was analyzed by histological and immunohistochemical methods. The effect of the NO donor on the cognitive recovery was evaluated through the object recognition task. Results showed that SAP decreased the novel object exploration, which could be due to the reduced cholinergic cellular population in the lesion site and MOLS was able to avoid the progression of damage in this area. The single dose of MOLS used in this study increased the exploration time of novel object. Previously, we demonstrated that MOLS administration produced the recovery of the basal levels of NOS activity in prefrontal cortex and striatum regions, which could antagonize the SAP-related memory impairments. Results suggest that MOLS could be acting as a modulator of nitrergic system, promoting the cognitive recovery in the model of cholinergic denervation induced by SAP. 2+ 2+ 3+ 2+ EFFECT OF CU , FE , CR , CD AND H2O2 ON CATALYTIC ACTIVITY OF ACETYLCHOLINESTERASE AND ACETYLCHOLINE IN VITRO Hernández Rodríguez a,b a,b c Maricarmen , Correa Basurto José , Mendez Garrido Armando , Rosales Hernández a Martha Cecilia Laboratorio de Biofísica y Biocatalisis. Escuela Superior de Medicina. a Instituto Politécnico Nacional Laboratorio de Modelado Molecular y Bioinformatica. SEPI. b Escuela Superior de Medicina. Instituto Politécnico Nacional Laboratorio de Mediciones Magnéticas y Biofísica. Escuela Superior de Física y Matemáticas. Instituto Politécnico c Nacional Alzheimer Disease (AD). Thus are due to free radicals (FR) are generated by interacting H 2O2 and metals (Cu+2, Fe+2, Cr+3 and Cd+2). During the AD, these metals increased, and consequently the FR, which could modify the catalytic activity of AChE. In this way, the main of this study was evaluated the AChE catalytic in presence of Cu2+, Fe2+, Cr+3, Cd+2 and H2O2 measuring the ACh concentrations. The results showed that metals and H2O2 hydrolyze ACh, being higher with the H2O2 than with metals. While, AChE activity decreased when metal and H 2O2 were combined being more evident with Fe2+. By using Cu2+, there was a significant statistical modification with 400 mM of Cu2+ and 100 mM of H2O2. The Cd2+ and Cr3+ followed a similar behavior, decreasing the AChE activity, where the limiting factor was H2O2 concentration. Agree with these results , the FR generation decrease the AChE activity, therefore, the ACh concentration available will be higher in the synaptic cleft, however it doesn´t occurs because the metals and the H 2O2 decrease ACh concentration , offering an explanation of the deficit in the cholinergic system in patients with AD. Our research group offers grateful to Conacyt 84119, COFAA 132353, and IPN for the financial support to development this work. 111 EFFECT OF THE DECOCTION OF Urtica dioica ON THE PROLIFERATION IN VITRO OF 1 HEMATOPOIETIC CELLS FROM ANEMIC AND HEALTHY MICE. Herrera-Solis, S., 1 1 1 2 1 Tapia-Aguilar, R., Flores-Sáez, J.L., Vega-Avila, E., Santana-Carrillo, J., Velasco1 2 Lezama, R. Departamento de Ciencias de la Salud. Herbario Metropolitano ―Ramón Riba‖. Universidad Autónoma Metropolitana-Iztapalapa. México, D.F. CP. 03401. [email protected] Urtica dioica is an annual or perennial plant widely distributed in Mexico. In folk medicine the plant is used by the Indian Raramuris as antianemic in pregnant women. In previous work we reported that the decoction of the plant counteract iron-deficiency anemia in pregnant female mice. The purpose of this investigation is to evaluate the hematopoietic activity in vitro of the decoction and its fractions. The decoction was chemically fractionated with hexane, dichlorometane, methanol. These fractions along with the residual aqueous, and the row decoction were added to cultures of hematopoietic cells from healthy and anemic female mice of CD1, distributed in groups A, B, and C with 10 animals each one. Anemia was induced in groups A and B by bleeding twice a week during for 15 days, Group C was the healthy control. On day 15 all mice were sacrificed and bone marrow and spleen cells were cultured with 1,10, 100 µg/ml of the decoction and its fractions (Group A), 5,10,20 µg/ml of FeSO4 for Group B, and pokeweed mitogen for Group C, respectively. All cultures were incubated in a CO2 atmosphere for 72 hr. Decoction stimulated significantly the proliferation of spleen cells from healthy mice, fractions showed lower hematopoietic activity than the raw decoction. The stimulant activity of decoction on spleen cells from anemic mice was lower than those from healthy mice. However, in both cases the activity was equivalent to cultures treated with FeSO4 or pokeweed mitogen. Except, the concentration of 100 µg/mL of dichlorometane fraction, that inhibited the proliferation of bone marrow cells from healthy mice, all others stimulated the cell proliferation. Results in vitro correlate with the hematopoietic activity of the plant in vivo, which in turn supports its popular use as antianemic. PHARMACOKINETICS AND BIOAVAILABILITY OF PIOGLITAZONE IN MEXICANS WITH 3 1 DIABETES MELLITUS TYPE 2: PILOT STUDY. Ibarra-Cázares A , Frías-Zepeda E , 2 4 1 1 Ramírez Flores E , Salas-Pacheco J , López-Guzmán O , Lozano- Guzmán E , Vértiz1 1 2 Hernández A . Facultad de Ciencias Químicas-UJED, Clínica de la Secretaria de Salud en 3 4 Peñón Blanco, Dgo, Facultad de Estudios Superiores (FES)-Zaragoza UNAM, Instituto de Investigaciones Científicas-UJED. Pioglitazone is an agent who belongs to class of thiazolidinediones, in recent years, due to variation in genetics condition and environmental conditions, the pharmacokinetics has received increasing attention in different populations. The aim was to determine the pharmacokinetic of pioglitazone in Mexicans of the state of Durango (Peñón Blanco Dgo) with diabetes mellitus type 2. The study groups were established by 24 patients with diabetes mellitus type 2 and 13 healthy subjects, all volunteers took a 30 mg pioglitazone tablet. The blood samples were collected of 0.0 to 36.0 hours and the pioglitazone was analyzed in the plasma by HPLC with a UV detector to 269 nm. The pharmacokinetics results were: (1) Volunteers with DM2: Cmáx (1.073 ± 0.5838 µg/mL), Tmáx (2.145 ± 1.0681h), Kel ( 0.066 ± 0.0544 h-1), ABC0-∞ (13.899 ± 5.3112 µg.h/mL)*, t½ ( 15.14 ± 8.77 h), Cl ( 2.479 ± 3.4343 L/h), Vd (50.0 ± 65.9806 L) y (2) Controls: Cmáx.( 0.934 ±0.087 µg/ml), Tmáx (0.934 ± 0.087 h), Kel (0.086 ± 0.015 h-1), ABC0-∞ (10.301± 0.873 µg.h/mL), t½ (10.87 ± 1.52 h), Cl ( 2.550 ± 0.213 L/h), Vd (37.068 ± 4.530 L). The study showed that ABC0-∞ was higher in the group with diabetes mellitus type 2 by 3.598 µg.h/mL respects to group control. In other sense, is shown that population of controls are different in some pharmacokinetics parameters (Cmax, ABCo-∞, Kel, Cl) with others populations (Chinese, Tai and Pakistani). This difference can due to specific factors that are related to polymorphism presence at the CYP3A4 and/or CYP2C8, to environmental factors such as arsenic (drink water). Thereby is suggested that the populations are pharmacokinetically differents when were referred to control group compared with diabetes mellitus type 2 and control group with other populations. 112 OCULAR AND SYSTEMIC ADVERSE EFFECTS OF OPHTHALMIC AND NON OPHTHALMIC MEDICATION: A SYSTEMATIC REVIEW. Consuelo Izazola-Conde1, Diego Zamora-de la Cruz1, Guadalupe Tenorio-Guajardo2. Departamento de Farmacología. Facultad de Medicina UNAM1. Servicio de Oftalmología. Hospital General de México, SS2. Information related to drug adverse effects caused by ocular medications, both, topical and systemic, has increased throughout the decades, the same occurs with information about ocular side effects of systemic administered drugs for non ophthalmologic indications. Objective: to quantitatively and qualitatively review the medical literature through the last four decades about drug induced adverse effects of ocular drugs and ocular toxicity of non-ocular drugs. Methodology: a bibliographic systematic review was performed with the following terms: ―drug treatment‖ ―drug therapy‖ ―ocular adverse effects‖ ―ocular side effects‖ ―ocular toxicity‖ ―systemic side effects‖ ―systemic adverse effects‖ ―systemic toxicity‖ ―ocular drug‖ ―ophthalmic drug‖ using Boolean operators such as: ―OR‖, ―AND‖ & ―NOT‖, searches were focused on the following issues: 1.Ocular side/adverse effects of ophthalmic drugs; 2. Ocular side/adverse effects of systemic drugs and 3. Systemic side/adverse effects of ophthalmic drugs. Pubmed was used to perform the searches, including as limits: species, human and field tag, abstract/title, dates from 01/01/1971 to 31/12/2010. A subselection of references was chosen, discarding articles that were irrelevant for the issues listed above. Results: Information about ocular side/adverse effects of ophthalmic drugs is the largest of the three. Adverse effects of adrenergic α2agonists, adrenergic βantagonists, quinine derivatives, antituberculous agents have been published throughout several decades. Adverse effects of newer drugs such as amiodarone, phosphodiesterase 5 inhibitors, antiepileptics, tamoxifen, and its interactions have been published mainly in the last two decades. Discussion: It is necessary to stress the importance of dissemination of knowledge among physicians related to adverse effects of drugs on the eye, topically and systemically administered and also about the possible systemic effects of drugs given as ophthalmic medication. AGEING, HEALTH AND MEDICINAL CONSUMPTION IN A SAMPLE OF ACADEMIC 1 EMPLOYEES AT A MEXICAN UNIVERSITY. Consuelo Izazola-Conde , Verónica Montes de 2 3 1 Oca Zavala , Elizabeth Santiago . Departamento de Farmacología, Facultad de Medicina , 2 3 Instituto de Investigaciones Sociales , Facultad de Ciencias , UNAM Population ageing is a singular phenomenon in each country and in different social groups. In a first approximation to study ageing perspectives of faculty employees, teachers and researchers at a Mexican university, we have explored their physical, mental and social conditions, style of life, job stress and ageing experience. Explore health status and medicines consumption among a sample of academic employees over 40 years of age at a Mexican university. Method: analysis of answers to an on line survey in a random sample of academic employees, 40 years and older, who work at the National University of Mexico. The 179 items survey was answered from November 2009 to October 2010, by 240 randomly selected academic employees. A section of the questionnaire was oriented toward health issues. We analysed reported illness, self-perception of health status and medicines consumption. Findings: Body systems involved more often among those who report any kind of disease, were: circulatory and endocrine and/or metabolic, followed by osteomuscular and digestive. Medicinal drugs were consumed in the last two weeks by 52% of respondents, among these, vitamins were consumed by 28%, drugs for pain by 17%, drugs for high blood pressure by 14%, drugs for high cholesterol by 13%, antibiotics by 8%, drugs for diabetes by 5%, cold medicines by 4%. Discussion: It is suggested that medicinal drugs may not be consumed in situations in which they are indicated, such as in hypercholesterolemia and possibly in hypertension and diabetes. Others, such as vitamins are frequently utilized. Research and interventions should be directed toward better utilization of medicinal drugs. 113 BIOACTIVITY-GUIDE ISOLATION OF HYPOGLYCEMIC CONSTITUENTS OF Ibervillea sonorae (S. WATSON) GREEN ROOTS COLLECTED IN CUMURIPA-PORVENIR, 1,2 1 SONORA, MÉXICO. Angel Jardón Delgado , Mariano Martínez Vázquez and Gil Alfonso 2 1 2 Magos Guerreo Institute of Chemistry and Department of Pharmacology , School of Medicine, University National Autonomous of Mexico. ([email protected]). The powder in capsules of root from Ibervillea sonorae (Curcubitaceae) have been widely used in the Mexican traditional medicine for the treatment of type 2 diabetes. Previous study on their antidiabetic properties of the root of I. sonorae has revealed that the nature of their active principles is a numerous mixture of monoglycerides and of fatty acids 1. Recent results from our laboratories, however, have led to the hypothesis that non-fatty constituents play an important role. The aim of our studies was to investigate the hypoglycemic activity de several extracts obtained with hexane, ethyl acetate, methanol and water from I. sonorae roots in healthy and alloxan-diabetic mice and to determine the compounds responsible for the observed effects in those extracts. In contrast with previous investigation, this study was conducted with I. sonorae root collected at Cumuripa-Porvenir municipality of Cajeme Sonora, México City. Results showed that the ethyl acetate extract exhibited the highest hypoglycemic effect in healthy and alloxandiabetic mice. The bioassay-guided fractionation of the ethyl acetate extract led to isolation of the active non-fatty containing fraction. The isolation of the activity compounds was carried out using column chromatography and preparative plates. The structural assignments of a non–fatty pure compound were based on NMR of 1H and 13C and mass spectrometry analysis. In this presentation, the isolation, identification and hypoglycemic activity of the extracts and of a compound isolated will be discussed. Referencie:1 Hernández Galicia, E. et. al. (2007) Monoglycerides and fatty acids from Ibervillea sonorae root: isolation and hypoglycemic activity. Planta Medica; 73: 236-240. MODIFICATION OF CADHERINS EXPRESSION IN MURINE MELANOMA MODEL BY 1 1 DAPHNETIN. Fausto Alejandro Jiménez-Orozco , Víctor Hugo Rico Urbina , Francisco 2 1 Jiménez-Trejo , María Juana García-Mondragón , Amelia Maldonado-Espinoza, Miguel 3 1 1 Ángel Herrera Henriquez , Nicandro Mendoza-Patiño , JJ Mandoki . [email protected] 1 2 Departamento de Farmacología, Facultad de Medicina UNAM. Departamento de Biología, 3 Facultad de Química, UNAM. Departamento de Biología Celular y Tisular, Facultad de Medicina UNAM Cadherins are a calcium-dependent cellular adhesion protein. During tumoral processes, the expression of cadherins diminishes, causing increases in the invasive processes and in the methastasis. Daphnetin (6, 7-dihydroxycoumarin) is a secondary metabolite in several plants used in folk medicine for inflammatory and allergic diseases. Previously, we have observed that daphnetin has in vivo low antitumor activity per se,. In the present work we (1) characterized the expression of E-cadherin and N-cadherin in mice tumors using specific antibodies for each marker; (2) we also evaluated the change expression of both proteins in the tumor of daphnetintreated mice respect to tumor induced control in mice. Male C57BL/6 mice, 6-7 weeks of age (n = 8 animals per group in each experiment). Daphnetin was administrated via oral (20 or 40 mg/kg/day) daily and after two weeks, 105 B16-F10 murine melanoma cells were injected subcutaneously in order to induce a primary tumor. After two weeks, tumor samples were obtained and were assayed according inmunofluoerescence protocols. In the control tumors, the mark of Ncahdherin was localizated in the cellular plasma membrane as. In contrast, E-cadherin had a diffuse plasmatic localization pattern with less intensity comparing with N-cadherin. In the tumors of daphnetin treated mice, at the doses of 20 mg the expression of N-cadherin diminished respect to controls. At doses of 40 mg/kg/day the expression of N-cadherin increased when compared to the control. In the case of E-cadherin, no important changes were observed in the intensity of the expression, but at the dose of 40 mg a better localization of the protein in the cell membrane was seen. These results indicate that daphnetin induce a doses dependent increase of N-cadherina, whereas in the case of E-cadherin only at high doses contribute to the relocalization. This effect cut be important as coadjuvant in the melanoma therapy. Supported by PAPIIT/UNAM IN209010. 114 EXPRESSION OF RNAM OF TRYPTOPHAN HYDROXYLASE IN TASTE BUDS OF THE RAT CIRCUMVALLATE PAPILLA. Blanca E. Juárez Muñoz and Rosalio Mercado Camargo. PIMCB- Facultad de Químico-Farmacobiología, Universidad Michoacana de San Nicolás de Hidalgo. Morelia, Michoacán. México. The neurotransmitter serotonin (5-hydroxytriptamine or 5-HT) mediates wide variety of functions such as mood control, sleep regulation, food intake, and sexual behavior, also has been involved in developmental events as a trophic factor. Serotonin is synthesized centrally by serotoninergic neurons located at the raphe nuclei and peripherically by enterochromaffin cells of the intestine. Serotonin precursor is the essential amino acid L-tryptophan. The ratelimiting step for the synthesis of serotonin is catalyzed by tryptophan 5-hydroxylase (TPH), of which, we know there are two isoforms (TPH1 and TPH2). Numerous studies have been demonstrated the presence of serotonin in cells belonging to the taste system in several species. Taste buds are cluster forming the taste papillae’s: fungiforme, foliate and circumvallated papillae. To date, it is unknown which isoforms of the TPH is expressed in the circumvallated papillae and its ontogeny. So, the aim of the present study, was examined the expression of the RNAm of TPH during of development of the rat circumvallate papilla. Expression of RNAm of TPH1 and TPH2 were determined by RT-PCR in rat embryonic 15, 17, and postnatal P0, P60 circumvallate papilla. Results showed the expression only of the RNAm of the TPH1 isoform as early 15 days of their embryonic development and maintain its expression into adulthood. These results support the hypothesis of the presence of the serotoninergic system in the lingual epithelium. Keywords: Serotonin, Taste Buds, Tryptophan 5-hydroxylase, Development. This work was partially supported by: CIC-U.M.S.N.H.(2011), CONACyT: 30489 EVALUATION OF CYSTICIDAL ACTIVITY OF NEW DERIVATIVES OF 5(6)1 CARBOXAMIDES OF CARBENDAZIM. Juárez Rocha Victorino , Palomares Alonso 2 3 3 Francisca , Hernández Luís Francisco , Melchor Doncel Silvia , Palencia Hernández 4 2,3 1 Guadalupe , Jung Cook Helgi . Universidad Autónoma Metropolitana, Xochimilco. 2 Laboratorio de Neuropsicofarmacología, Instituto Nacional de Neurología y Neurocirugía. 3 4 Facultad de Química, UNAM. Laboratorio de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía, México, DF In the search of new molecules with cysticidal activity a set of four 5 (6)-carboxamides of carbendazim were synthesized. These molecules have the molecular requirements to exhibit activity that was found in previous study. Therefore the aim of this study was to evaluate their in vitro cysticidal activity using Taenia crassiceps cysts and albendazole sulfoxide (ABZSO) as reference drug. The parasites were deposited in cell culture dishes with culture medium containing each molecule (0.28 - 3.5M) and were incubated at 37°C with 5% CO2 during 11 days. The mortality of the cysts was recorded every third day using an inverted light microscope. Each experiment was run by triplicate. The effective concentration 50 (EC 50) was calculated from concentration-response curves, using a nonlinear regression analysis. Our results showed that all craboxamides exhibited cysticidal activity. The values EC 50 were: AOA1: 11.64M (9.06-16.07), AOA12: 9.18M (5.98-12.16), AOA70: 6.33M (5.58-7.21) and MEDS: 1.08M (0.78-1.5). The analogue MEDS was the most potent among the derivatives but less potent than ABZSO: 0.28M (0.19 to 0.43). This molecule could be a new pharmacological alternative for the treatment of cysticercosis, therefore; it is important to continue with its further evaluation, assessing its in vivo efficacy and biopharmaceutical properties. 115 HYPOGLYCAEMIC EFFECT OF AQUEOUS EXTRACT OF CARICA PAPAYA LEAF IN 1 1 STREPTZOTOCIN-INDUCED DIABETIC RATS Juárez-Rojo IE , Miranda-Osorio PH , 1,2 1 1 3 Ramón-Frías T , Aguilar-Mariscal H , Blé-Castillo JL , Rodríguez-Hernández A , Díaz4 2 1 Zagoya JC , Bermúdez-Ocaña DY . División Académica de Ciencias de la Salud, 2 Universidad Juárez Autónoma de Tabasco. División Académica Multidiciplinaria de 3 4 Comalcalco, UJAT. Hosp. IMSS Xalapa, Veracruz Fac. de Medicina, UNAM. Carica papaya belongs to the family of Caricaceae and several species of Caricaceae have been used as remedy against a variety of diseases. The present study was to determine the effect of aqueous extract of C. papaya leaf in streptozotocin (STZ)-induced diabetes in rats. Diabetes was induced in male Wistar rats (250-300g) using a single intraperitoneal injection of STZ (60mg/Kg). Experimental groups of non diabetic (ND) and diabetic (D) rats received aqueous extract of C. papaya doses (3.5, 7.5 and 15 g/500 ml) for 30 days while other group ND and D received water for the same length of time. At the end of treatment, the animals were sacrificed by decapitation and blood sample was collected. Level of serum glucose, cholesterol, triglyceride and HDL-cholesterol concentrations were determined by using spectrometric methods. Level of insulin was assayed by an ELISA kit. Treatment with extract of C. papaya reduced a dose-dependent manner level of glucose in D rats. Plasma insulin levels were increased by treatment in ND but not modify in D rats. Additionally, C. papaya diminished the triglyceride level in D rats. The results indicated that aqueous extract of C. papaya showed a clear hypoglycaemic effect in diabetic rats. Such an effect cannot be mediated by an enhanced insulin secretion. POPULATION PHARMACOKINETICS OF CYCLOSPORINE IN THE EARLY PERIOD OF 1 POST RENAL TRANSPLANT (RT) IN PEDIATRIC RECIPIENTS. Ismael Lares-Asseff, 2 1 3 1 Samuel Saltzman, J. David Urbina Álvarez, Gabriela Guillé P., Martha Sosa M., 1 1 3 1 Verónica Loera C., Carlos Galaviz H., Alejandra Toledo. Instituto Politécnico Nacional, 2 CIIDIR-IPN Unidad Durango. Jefe del Servicio de Nefrología y la Unidad de Trasplante 3 Renal del Instituto Nacional de Pediatría, (INP). Departamento de Farmacología del INP. Cyclosporine (CsA) is an immunosuppressive agent, selectively adjust the role of helper T lymphocytes. To establish differences between plasma concentrations of CsA at steady state in pediatric patients treated with acceptance or rejection of renal transplantation and to determine population pharmacokinetic parameters of CsA in pediatric patients. We included 64 patients between 3 and 18y, belonging to the renal transplant program of the INP. The first 59 days of CsA concentrations were 731, with acceptance of RT, 262 (81%) were subtherapeutic, 55 (17%) therapeutic and 6 (2%) toxic vs patients with toxic rejection of RT, in whom 309 (75 %) were subtherapeutic, 78 (19%) therapeutics and 21 (9%) toxic statistically significant differences p = 0.04. From 60 to 180 days were 794 concentrations, which in patients with acceptance of RT: 233 (77%) were subtherapeutics; 63 (21%) therapeutics and 5 (2%) toxics vs patients with rejection of RT who: 357 (72%) were subtherapeutic, 98 (20%) therapeutics and 38 (8%) toxic with p = 0.01, statistically significant. Of > 180 days were 432 CsA concentrations, in patients with acceptance of RT; 104 (59%) were subtherapeutic; 60 (34%) therapeutics and 12 (7%) toxic vs patients with rejection of RT in which 138 (54%) concentrations were subtherapeutic; 89 (35%) therapeutics and 27 (11%) toxic p = 0.34, which were not significant. Conclusions: 1.-There are significant differences between plasma subtherapeutic, therapeutic and toxic CsA concenbtrations within the two groups and among subjects with rejection and acceptance of RT were more marked toxic concentrations in patients with rejection RT, which were significantly higher, so they could not fit a pharmacokinetic model. 2.- To adjust the dose should be individualized and based on pharmacokinetic parameters of this population. 116 INTERSPECIES DIFFERENCES IN THE OVARIECTOMY RECOVERY OF MICE OF SOME HAEMOSTATIC MARKERS. Cristina Lemini, Ruth Jaimez, Ávila y Martha Medina Jiménez. Departamento de Farmacologìa, Facultad Universidad Nacional Autónoma de México. Av. Universidad No. 3000, Delegaciòn Coyoacán, México, D.F., México. [email protected] RATS AND Maria Estela de Medicina CP 04510, Rodent ovariectomy is used as a model to test estrogenic activity, the haemostatic changes after this surgery, have not been fully characterized yet. This work evaluated changes in uterus and in the coagulation tests: prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin clotting time (TT), and fibrinogen concentration (FIB) after ovariectomy of adult female CD1 mice and Wistar rats. Uteri involution was determined by uterine weight (Uw), before ovariectomy (control) and on days 1, 3, 5, 7, 9, 16, and 21 after it. PT, aPTT, TT and FIB were estimated the same days, using modifications of conventional human techniques. For both species ovariectomy decreased Uw since day 1 to day 9, the uterine involution from day 9 to 21 did not show significant changes and reached their Uw lowest values. After day 1 from surgery the mice hemostatic parameters changed (PT= +10%(P<0.02); aPTT= +53%(P < 0.001);TT= 24%(P<0.005); and FIB= +67%(P<0.0001). Rats at is stage, showed significant changes only in TT= -13%, (P<0.01) and FIB (+65%; P<0.0001). In mice PT from days 3 to 21 were decreased to ~11% (P<0.01) without recovering to control values. The rats PT values slightly increased from day 5 to day 9 (2%; P<0.05) returning to control values on day 16. Mice aPTT values decreased at days 7-9 to 14-15% (P<0.05), and on day 21, 24% (P<0.05). The rats aPTT values decreased (23%, 18%, and 20%; P<0.01) on days 5, 7, and 16, respectively recovering after 21 days. After day 21, mice TT was still decreased by 14% (P<0.01) without recovery. FIB recovery to control values was after 9 days for mice and after 16 for rats. Ovariectomy differently altered mainly PT and aPTT of both species. The observed changes were more pronounced in mice, suggesting species inherent hemostatic differences that need to be taken into account in the experimenal design. GENDER DIFFERENCES IN THE RESPONSE TO CHRONIC TREATMENT WITH 17ßESTRADIOL AND THE 17ß-AMINOESTROGEN PENTOLAME ON HEMOSTASIS IN RATS. Cristina Lemini,* Ruth Jaimez, Martha Medina Jiménez and Marìa Estela Ávila. Departamento de Farmacologìa, Facultad de Medicina Universidad Nacional Autónoma de México. Av. Universidad No. 3000, CP 04510, Delegación Coyoacán, México, D.F., México. *[email protected] This work evaluated the effects of chronic treatment (CT) with 17ß-estradiol (E2) and the 17ßaminoestrogen pentolame (AEP) on prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen concentration (FIB) in male and ovariectomized (Ovx) Wistar rats exploring gender pharmacological response differences. Rats (n=12-18) were treated every third day during three months, with: E2 (1, 10, 100 µg/kg), AEP (1, 10, 100, 500 µg/kg) or vehicle (propylenglycol 1 ml/kg). PT, aPTT, TT, and FIB were measured according to previously standardized techniques. In male rats E2 increased PT (4-7%;P<0.05), whereas, in Ovx rats E2 and AEP decreased it (E2=3-4%; AEP=5-9%; P<0.05). E2 decreased males aPTT (9%; 100g/kg; P<0.05) and AEP dose dependetly increased it (5-16%;P<0.05). In Ovx animals, E2 did not induce significant changes on aPTT, whereas AEP increased it (8-13%;P<0.05). In male and Ovx rats E2 and AEP decreased TT. In male: E2 and AEP decreased it ~5% with 100 and 500g/Kg respectively (P<0.05) and in Ovx, both steroids decreased it in a dose dependent manner being E2 more potent than AEP (E2 12-23%; AEP 6-13%;P<0.05). E2 and AEP decreased FIB, the effects of E2 were similar to those elicited by AEP. The FIB decreases were more pronounced in male (15-18%) than in Ovx (3-15%), however in Ovx the effects were dose dependent. The FIB significant decreases produced by both estrogens on Ovx rats were obtained with the lowest doses with a tendecy to be reverted by dose increasing. E 2 and AEP chronically administered induced differential responses of the PT and aPTT hemostatic parameters of male and Ovx showing a gender influence on the pharmacological response of estrogens on the hemostatic system. 117 SYNTHESIS, CHARACTERIZATION AND ACUTE TOXICITY STUDIES OF AN 1 ARYLETHANOLAMINE DERIVATIVE WITH SEDATIVE PROPIERTIES. López-Cabrera Y , 1 1 1,2,3 1,3 Leal-Gutiérrez MA , Lascari-Jiménez EC , Correa-Basurto J , Trujillo-Ferrara JG , 1,2 1 2 3 Soriano-Ursúa MA . Departamentos de Bioquímica, Farmacología y Fisiología y Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, México ([email protected]). Arylethanolamine compounds are commonly applied in the modulation of activity of biological systems. It is well-known that this kind of compounds has action in adrenergic or dopaminergic systems in mammals. In this work, we synthesized an arylethanolamine boron containing compound which had shown high affinity by adrenoceptors in previous in silico studies. Then, we characterized the compound by using melting point determination, thin layer silica chromatography; infrared, raman and nuclear magnetic resonance spectroscopy. With the aim of determine the acute toxicology profile (lethal dose) of the compound, this was intraperitoneally administered in male CD1 mice weighting 25 to 30 g. Thus, we found a LD50 of 862 mg/kg, which is higher than determined for other arylethilamines. However, we also observed a sedative effect in mice which were administered with dose greater than 1 mg/kg. Additional studies are necessary for elucidating the mechanism for this sedative effect. MODIFICATIONS OF FUNCTIONALITY OF RAT AORTA β-ADRENERGIC RECEPTORS 1,2 1,3 1 DURING DEVELOPMENT. López-Canales O , López-Canales J , Padilla-Pérez J , 2 11 Escalante-Acosta B ,Castillo-Henkel C Seccion de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina, I.P.N. Plan de San Luis y Díaz Mirón, Col. Casco de Sto. 2 Tomas, México-11340, México, D.F. ([email protected]), Centro de 3 Investigación y Estudios Avanzados del IPN, Instituto Nacional de Perinatología During the development of the rat there are changes in the participation of adrenergic receptors in the regulation of vascular tone. Thus it has been found a reduction of the aortic β-adrenergic response when adolescent and adult rats were compared, although the relative participation of each subtype of β-adrenergic receptor in it was not yet completely evaluated. With the aim of provide additional information about this topic, responses in aorta from rats of 3 weeks, 6 weeks (prepuberty in both cases) and 15 weeks old (adult) precontracted with -6 -9 -4 phenylephrine (10 M) and relaxed with isoproterenol (10 -10 M, non-selective βadrenergic receptor agonist) in the presence or absence of subtype-selective β-adrenergic antagonists, were studied. The results shown that CGP 12177A ( 1-adrenergic antagonist) did not modify the isoproterenol response in any age-group of rats. On the other hand, pretreatment with ICI 118,551 ( 2-adrenergic antagonist) inhibited the isoproterenolresponse in the three groups of rats but the antagonism was competitive in the younger and non-competitve in the adult animals. Interestingly, a higher inhibition of the isoproterenol response was observed when CGP 12177A and ICI 118,551 where administer together suggesting a synergic interaction between the two sybtypes of receptors. On the other hand, BRL 37344 ( 3-adrenergic receptor agonist) elicited relaxation only in aortic rings from prepuberty-rats. In conclusion, changes in the β-adrenergic receptor mediated aortic response during development of the rat is associated with loss of β3-adrenergic subtype participation and change in the affinity of the β2-adrenergic subtype of receptors. Further experiments are nedded to explain the potential synergic interaction between β1- and β2adrenergic subtypes observed when the two respective antagonists were employed together 118 THE ETHANOLIC EXTRACT OF Trichaptum biforme PRESENTS ANTINOCICEPTIVE AND ANXIOLYTIC PROPERTIES. López-Galindo G., Hernández -García A., Ortiz-Butrón R., Cortés-Mercado V., and Cano-Europa E. Laboratorio de Neurobiología. Departamento de Fisiología de la Escuela Nacional de Ciencias Biológicas-IPN. México, DF. [email protected] It was evaluated the antinociceptive and anxiolytic properties of ethanol extract and fractions completely polar, moderately polar and nonpolar of Trichaptum biforme mycelium. The mycelium was grown in a culture for Trichaptum biform contained in a 10 L bioreactor for 15 days. It was made an ethanol extraction of the mycelium and fractionated with hexane, ethyl acetate and ethanol. NIH male mice were used (25-30 g), which were pre-treated with 10, 30, 50, 100, 150, 300 and 450 mg/kg ip of the crude extract or the fractions. It was assessed the antinociceptive activity by phasic pain test and anxiolytic activity using open-field exploratory activity, elevated plus maze and perforated board paradigms. The results obtained shows that the whole extract and the fractions decrease the number of abdominal constrictions. Regarding the anxiolytic activity, only the dose of 450 mg/kg was effective. The whole extract and the fractions of Trichaptum biform present antinociceptive and anxiolytic activities. Funded by grants from the SIP-IPN 20100478 and 20110473. TIME-DEPENDENT REVERSAL OF RENAL AND AORTIC HISTOLOGICAL CHANGES IN AORTIC COARCTATION-INDUCED HYPERTENSION IN RATS I. LÓPEZ-ISLAS AND J.A. TERRÓN. Departamento de Farmacología, CINVESTAV-IPN, Apdo. Postal 14-740, Zacatenco 07000, México D.F. Structural cardiovascular changes are observed in animal models of renovascular hypertension, and angiotensin II (ATII) is known to promote widespread trophic actions. We analyzed the microscopic morphology of kidneys, aorta and heart in rats with sham operation (SO), and aortic coarctation for 7 (AC7) and 14 (AC14) days. Diastolic blood pressure (DBP) and hear rate (HR) (recorded from the carotid artery) and plasma levels of ATII (quantified by immunoassay) were also measured. Aortic coarctation increased DBP (values for SO, AC7 and AC14 were, respectively, 101±2, 132±4* and 136±2* mm Hg; *P<0.05 vs SO) and, in AC14, also HR (values for SO, AC7 and AC14 were, respectively, 366±9 372±17 and 415±11** bpm; **P<0.05 vs SO and AC7), as well as plasma ATII (values for SO, AC7 and AC14 were, respectively, 127±0.3, 132.6±1.6* and 130.5±0.6* pg/ml; *P<0.05 vs SO); DBP and plasma ATII, however, did not differ in both groups of coarcted animals. Left Kidneys from AC7 developed overall necrosis which almost fully reverted in AC14. Hypertrophy and hyperplasia (i.e. increased number of medial smooth muscle layers) was observed in aorta of coarcted animals with hyperplasia -but not hypertrophy- being partially reverted in AC14; these changes reflected as an increased wall/lumen relationship (0.168±0.009, 0.248±0.018* and 0.300±0.050* for SO, AC7 and AC14, respectively; * P<0.05 vs SO). In the heart, AC7 and AC14 resulted in partial and overall hypertrophy, respectively. Data may suggest a link between increased circulating ATII and hypertension, renal necrosis, vascular hypertrophy and hyperplasia, and cardiac hypertrophy. With the exception of hypertension and vascular and cardiac hypertrophy, these changes are reverted probably as a result of compensatory mechanisms in AC14 that need more study. Results might shed light into early mechanisms of aortic coarctation-induced hypertension. Supported by CONACyT grant 57466. 119 ENDOTHELIUM DYSFUNCTION IN THE DIABETIC RAT IS REVERTED FOR INSULIN IN 1,2 3 3 1 VITRO. López-López G , León Palacios A , Atonal-Flores F , Hernández Cabrera J , Flores 3 1 2 3 Guerrero J.L . Facultad de Ciencias Químicas, Instituto de Fisiología, Facultad de Medicina. Benemérita Universidad Autónoma de Puebla, México. The main etiology for death and for a great percent of morbidity in patients with diabetes is vascular disease. Data suggest that diabetes is a risk factor for pulmonary hypertension. In addition, pulmonary arteries from diabetic rats showed impaired relaxant response to acetylcholine and an increase in superoxide production. Moreover, Insulin is known to be a systemic vasodilator but its effect on the pulmonary circulation is not fully known. The aim of the present study was to analyze whether insulin in vitro reverted endothelial dysfunction found in pulmonary arteries from diabetic rats. Methods. Male Sprague-Dawley rats were randomly divided into a control (saline) and a diabetic group (70mg/kg streptozotocin). After 6 wk, intrapulmonary arteries were cut into rings. To further determine the role of insulin in regulating vascular smooth muscle tone during diabetes, pulmonary artery rings with endothelium-intact were incubated with or without 100 nM insulin for 4 hour and then were mounted for isometric tension recording. After equilibration, rings were precontracted by -9 0.1µM phenylephrine, and concentration-response curves to insulin or acetylcholine (1x10 -4 1x10 ) were performed by cumulative addition. Endothelial function was tested by the relaxant response to acetylcholine.Results. We have shown that pulmonary artery vasodilatation with insulin occurs in a dose-dependent manner; also, insulin-dependent relaxation was similar in diabetic or control artery rings. With insulin in vitro completely normalized DM-induced endothelial dysfunction (DM 85 ±4% vs. control 80 ±3%). Conclusions. These effects could be clinically important for diabetic patients using insulin who have some chronic lung disease. THE ROLE OF THE SEROTONIN IN PULMONARY VASCULAR HYPERREACTIVITY 1,2 1 3 DURING DIABETES MELLITUS. López-López G , Santamaría Juárez C , Atonal-Flores F , 3 2 3 4 León Palacios A , Flores Hernández J , Flores Guerrero J.L , Pérez Vizcaíno F . 1 2 3 Facultad de Ciencias Químicas, Instituto de Fisiología, Facultad de Medicina. Benemérita 4 Universidad Autónoma de Puebla, México. Universidad complutense de Madrid, España. Diabetes Mellitus (DM) recently has been implicated as a risk factor in Pulmonary Arterial Hypertension (PAH). In diabetic rat induced-streptozotocin model, diabetes induces endothelial dysfunction in pulmonary arteries due to a reduction in the bioavailability of NO, an effect that might explain the link between DM and PAH. Serotonin is known to be a pulmonary vasoconstrictor but its effect during DM is not known. The aim of the present study was to analyze whether serotonin plays a role in the genesis of PAH diabetes induced. Methods. We studied the effects of serotonin in vitro on isolated rat pulmonary artery with endothelium-intact in a set up for isometric tension recording. DM was induced in male Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin (70mg/kg). 6-8 wk later, pulmonary artery rings from control and diabetic rats were isolated, and vascular responses to serotonin were obtained in the presence and absence of Ketanserin, SOD, Apocinin, Indometacin and NS398. The Fulton index (weight ratio:right ventricle/left ventricle + septum) was calculated to assess diabetes-induced right ventricular hypertrophy. Results. DM group shown hyperresposiveness to serotonin (Emax 101±3 vs. 50±2%). This effect is independent of the endothelium and was prevented by indometacin, NS398, SOD and apocinin. Right ventricular hypertrophy was indicated by the Fulton index (0.38±0.02 vs. 0.31±0.01). Conclusions. Our results further strengthen the link between diabetes and pulmonary hypertension, and appears to be related to COX-2 derived metabolites and NADPH oxidase-induced superoxide production. 120 EFFECTS OF TWO ANESTHETIC (PROPOFOL OR KETAMINE-XYLAZINE) PROCEDURES ON THE HEART RATE VARIABILITY, IN DOGS. LOPEZ-RODRIGUEZ 1 2 3 MANUEL , RUIZ-VEGA HUMBERTO , FENTON-NAVARRO BERTHA , LETECHIPIA3 3 1 VALLEJO GRACIELA , CERVANTES MIGUEL . Facultad de Medicina Veterinaria y 2 3 Zootecnia. Facultad de Ciencias Fisico-Matemáticas ―Mat. Luis Manuel Rivera Gutiérrez‖. Facultad de Ciencias Médicas y Biológicas ―Dr. Ignacio Chávez‖, Universidad Michoacana de San Nicolás de Hidalgo. Morelia, Michoacan. MEXICO. The stability of the autonomic tonus is an important condition during anesthesia and surgical procedures, because of its influence on cardiac and respiratory functions. The quantification of heart rate variability (HRV), both in the time and frequency domains, is a proven procedure to evaluate the sympathetic / parasympathetic balance. The aim of the present study was to evaluate the autonomic activity in dogs under two different anesthetic procedures (Propofol or Ketamine-Xylazine) through parameters of HRV. Twelve healthy dogs (age: 2-5 years; body weight: 6-8 kg) were used. Electrocardiographic recordings were made before and during propofol (5 mg/kg) or Ketamine-Xylazine (0.1mg/kg - 2 mg/kg) anesthesia. Electric signals were processed (prototype electric signal processor) to obtain the following parameters of HRV: standard deviation of the NN (R-R) intervals (SDNN) and the square root of the mean squared differences of successive NN intervals (RMSSD); as well as a power spectrum analysis of low (LF 0.05 a 0.15 Hz) and high (HF 0.15 a 0.40 Hz) frequencies. Statisticals comparisons of these parameters under the different experimental conditions were made by means of a two way ANOVA with repeated measures followed by MannWhitney and Wilcoxon tests. Analysis of data showed an increase in LF power (indicative of higher sympathetic / lower parasympathetic activity) under the anesthetic procedures (p=0.01), with higher values for Ketamine-Xylazine (p<0.05). Besides, a significant decrease of SDNN occurred under both anesthetic procedures, though Ketamine-Xylazine (125.82 ms to 30.01 ms) elicited a significantly higher decrease than Propofol (139.76 ms to 90.80 ms). These results suggest a better autonomic balance under Propofol than under KetamineXylazine anesthesia. LEAF HIDROMETHANOLIC EXTRACT OF Struthanthus venetus (BLUME) ATTENUATES THE METABOLIC SYNDROME INDUCED BY HIGH FRUCTOSE DIET IN 1 1 WISTAR RATS. Lorenzana-Jiménez, Marte , Magos Guerrero Gil Alfonso , Mendiola 1 2 3 3 Almaraz Lorena , Maldonado Jhon , Gijón Granados Enrique Gonzalez García Xaviera 1 3 2 Department of Pharmacology, Department of Physiology, School of Medicine, Institute of Chemistry, University National Autonomous of Mexico, México D.F. ([email protected]). In previous studies we have shown that the methanol extract from Struthanthus venetus (Sv) leaves, known as "graft or matapalo", induced hypotensive and cardiotoxic effects over the anesthetized rats. Moreover, the same extract also significantly decreased triglycerides and cholesterol blood levels. Supporting the use of botanical extracts as botanical drugs, in the present study we examined the effect of a hydrometanolic extract from Sv leaves on blood pressure, lipid profiles, and glucose of rats with metabolic syndrome induced by high-fructose diet. Two adult rat groups were studied: a control group received regular rodent Chow (Purina) and drinking water ad libitum and other fructose group was fed on 20% fructose diet and 20% solution in drinking water. After 8 weeks the fructose group developed signs of metabolic syndrome, including elevated abdominal fat deposition, abnormal plasma lipid profile, and hypertension. This last group showed that the hydrometanolic extract administered orally (310 mg/kg) everyday during two months, produces antihypertriglyceridemic and antihypertensive effects. In this last effect probably the polyphenol compound identified to NMR 1H and NMR C (CD3OD) as catechin, is included. These results suggest that the hydrometanolic extract of Sv contain polyphenols with potential properties to treatment of metabolic syndrome, which need further investigation. 121 ANTIINFLAMMATORY ACTION OF CAPSAICIN ON THE BRAIN IN ENDOTOXIN1 1 CHALLENGED MICE M.S Luevanos Raymundo , P.T. Villalobos-Gutierrez M .M.L. Miranda1 1 1 Beltran ,.O. Gutiérrez-Coronado [email protected] Centro Universitario de los Lagos; Universidad de Guadalajara The nervous system and the immune system mount a variety of essential, coordinated responses to danger. The immune system signals the brain to respond to danger of viruses, bacteria and parasites through and elaborate system, and communicate through neurotransmitters, endocrine hormones and cytokines. Cytokines have a pivotal role in orchestrating the inflammatory and are essential in restoring homeostasis. The proinflammatory cytokines, TNF-α and IL-1β can be considered the a multifunctional and pleiotropic cytokine due to its widespread effects on immune signaling, CNS functions, and its prominence in many disease states. Inhibition of their action in CNS may provide therapeutic benefits in several diseases. Different chemical structural types of natural products exhibit anti-inflammatory activity and are considered to be potential drug candidates against the inflammation-related pathological processes. The capsaicin a major ingredient of hot pepper, is considered to exhibit anti-inflammatory properties. BALB/c mice were exposed to LPS application (250µg/100g) in order to evaluate the anti-inflammatory activity capsaicin in CNS. Five different groups were used: (i) control group (none stimulus); (ii) LPS; (iii) LPSdexamethasone; (iv) LPS- capsaicin (1.28 µg/kg) and (v) vehicle control. The brain was added to 0.25–1.0 ml of cold Iscove’s culture medium containing 5% fetal calf serum and a cocktail enzyme inhibitor. Total protein was mechanically dissociated from tissue using an ultrasonic cell disruptor, sonicated samples were centrifuged at 14,000 rpm at 4°C for 10 min. Supernatants were removed and stored at 4°C until an ELISA was performed. Capsaicin after peripheral administration reduced TNF-α and IL-1β levels significantly p<0.001. As well as the releasing nitric oxide was significantly inhibited (p<0.005). These data suggest that the capsaicin can be block the production of pro-inflammatory cytokines and maybe inhibit iNOS. So this molecule may be promising drug for targeted inhibition inflammatory diseases. EXTRACTS FROM SARGASSUM HYSTRIX BUXIFOLIUM CHAUVIN INHIBIT THE PROLIFERATION OF CERVICAL CANCER CELLS THROUGH ARREST ON THE S STAGE OF THEIR CELL CYCLE. Luna-Cruz Norma A, Mendoza-Rodríguez Yolanda, Luna1 1 Nophal Angelica, Rubio-García Ricardo , Ávila-Ortiz Alejandrina Graciela , Corona-Ortega T, Weiss-Steider Benny y Rangel-Corona Rosalva. Laboratorio de Oncología Celular, 1 UIDDC, L-4 P.B. UMIE-Z, Herbario, Facultad de Estudios Superiores Zaragoza, UNAM. [email protected] The search for new anti-cancer drugs is one of the most prominent research fields of natural products. Active isolated compounds of a variety of alga have been studied with promising results. In this respect products obtained from the genus Sargassum, that is distributed in tropical coasts, have shown to posses antibacterial, antifungal and anti-tumor activity. This study was undertaken to evaluate if extracts from the Sargassum hystrix variety buxifolium Chauvi (ShbCh) brown alga, exclusive of the Gulf of Mexico, could inhibit the proliferation of human cervical cancer cell lines. For this purpose we used 20 different carotenoid extracts and evaluated their effect on the proliferation of INBL and CALO cell lines. Growth inhibition was evaluated through a crystal violet assay and cell cycle dynamics through flow cytometry. Our results showed that the extracts had growth inhibitory activity and that one of them (No. 8) presented the most potent activity against both cell lines. We also demonstrated that ShbCh extracts induced cell cycle arrest in the S stage and inhibited entering into G2. The present results could open a new field of anti-tumor research for ShbCh active compounds and their possible application on cervical cancer therapy. 122 PALLIATIVE TREATMENT WITH MORPHINE DRUG SUBCUTANEOUSLY IN PATIENTS WITH CANCER OF PALIA INSTITUTE OF GUADALAJARA-JALISCO Luna-Hernández 2 2 2 Ana Laura , Alvizar-Medina Alan Manuel , Valenzuela-Limón Olga Lidia , García2 1 1 MontalvoEliud Alfredo , García-Llamas Enrique , Escutia-Gutiérrez Raymundo , López3 2 1 López José Gustavo y Herrera-Huerta Emma Virginia . Centro Integral de Servicios 2 Farmacéuticos, Instituto PALIA, Zoquipan, Jalisco, Facultad de Ciencias Químicas, UV. 3 Orizaba, Ver. Facultad de Ciencias Químicas, BUAP. Puebla, Pue Introduction: In the palliative care of cancer treatment, the principal objective is to mitigate symptoms to improve quality of life in patients, one of the main symptoms is the pain, according to their nature can have huge differences, depending on its intensity goes from intolerable to tolerable. Objective: Justified palliative treatment with subcutaneous morphine in cancer patients in PALIA institute in the city of Guadalajara, Jalisco. Methodology: This study is descriptive, co-relational, prospective and observational. The universe are patients of the institute for palliative care PALIA, period June 2008 – July 2010, working with a non probability sample who was intentional, having the inclusion criteria, patients with a neoplasic disease, being older and having signed the informed consent. Results: Review the individual patient record, 92.3% reported pain as main symptom and is chronic in 88.5% of sample. Morphine was used as primary treatment in 42.3% of cases. Patients whose prescription consist analgesics primarily 76.9% of these, only 5% were treated with an analgesic that does not belong to opiates. Patients had other symptoms like nausea, vomiting and constipation they are suggested can be avoided making a change to subcutaneous rout. On the other hand, few drugs given in addition to morphine, 61.5% of patients receiving medicines for stomach, caused perhaps by the excessive oral administration, 34.6% received laxatives drugs, 26.9% consume drugs to prevent nausea and vomiting, which interfere with the success of the common rout, 53.84% of patients receiving more than one drug of these three categories. Conclusion: The dose of morphine is adjustable according to intensity of pain. Subcutaneous administration, for its accessibility from primary care, is the best alternative in the palliative treatment when the oral route is not possible, and allows the multidisciplinary team to make a comprehensive patient care. SYNTHESIS, ANTINEOPLASTIC ACTIVITY AND STRUCTURE-ACTIVITY RELATIONSHIPS OF NOVEL 5N-SUSTITUTED DIAZABICYCLIC AMIDES OF PHENYLACETYLRICINOLEIC ACID Axel Luviano, Itzen Aguiñiga, Reynaldo Tiburcio, * * Patricia Demare, Manuel López, Ivan Monsalvo, Edelmiro Santiago and Ignacio Regla Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), Batalla del 5 de mayo y Fuerte de Loreto, Ejercito de Oriente, Iztapalapa, México DF, 09230. *[email protected], [email protected] Cancer is a major problem of public health. In the search for new antitumoral drugs, a series of three new diazabicyclic amides derived from phenylacetylricinoleic acid were synthesized from castor oil and trans-4-hydroxy-(S)-proline using a chemoenzymatic method. These compounds were provisionally named PhAR-DBH-Me, PhAR-DBH-Bn and PhAR-DBH-EtOH. The antineoplastic properties of this compounds were evaluated in mouse leukemic cell lines P388, J774, WEHI-3, human leukemic cell line K562 and mouse normal bone marrow cells. The synthetic procedure involved base-catalyzed methanolysis of castor oil to afford methyl ricinoleate, phenylacetylation and regioselective enzymatic hydrolysis of the methyl ester to yield phenylacetylricinoleic acid (1,2). (1S,4S)-2-methyl-, (1S,4S)-2-hydroxyethyl- and (1S,4S)-2bencyl-2,5-diazabicyclo[2.2.1] heptanes were synthesized according to the literature (3). Finally, diazabicyclic amides PhAR-DBH-Me, PhAR-DBH-EtOH and PhAR-DBH-Bn were synthesized by reaction of phenylacetylricinoleic acid with (1S,4S)-2-alkyl-2,5-diazabicyclo[2.2.1]heptanes by the mixed anhydride method. The sulforhodamine B assay for cytotoxicity screening showed significantly high cytotoxic effects of PhAR-DBH-Me and PhAR-DBH-EtOH on leukemic cells and low toxicity toward mouse bone marrow cells. This remarkably selective cytotoxic effect highlights the antineoplastic potential of both new compounds. 123 ANTIHYPERTENSIVE AND VASORELAXANT EFFECTS OF A METHANOL EXTRACT AND ISOLATED COMPOUND FROM CHIRANTHODENDRON PENTADACTYLON (LARREAT) IN RATS. Magos Guerrero Gil Alfonso, Lorenzana-Jiménez Marte, Mendiola Almaraz Lorena, Escobar Ramirez Juan Luis. Department of Pharmacology, School of Medicine, University National Autonomous of Mexico, México D.F. ([email protected]). Chiranthodendron pentadactylon (Ch. p.) known as (―flor de manita‖ and ―macpaxochitl‖) is a plant commonly used in folk medicine to control heart disease and gastrointestinal disorders such as diarrhea and dysentery. Today, this plant for its medicinal properties is a species threatened with extinction. Aim of the study: Is assess the cardiovascular activity which supports the therapeutic use of Ch. p. to treat hypertension. Materials and methods: a methanolic extract from Ch. p. flowers (MEChpF), was evaluated on blood pressure of normotensive and hypertensive rats, in aortic rings preparation (ARP) and on perfused mesenteric vascular bed preparation (PMVBP). Results: Oral doses (100 mg/kg) or an intravenous dose (31 mg/kg) of MEChpF induced hypotensive and antihypertensive effects in normotensive and hypertensive rats, respectively. MEChpF shows vasorelaxation endothelium-dependent on the contraction induced by norepinephrine in ARP and PMVBP. This vasorelaxation is mediated by nitric oxide because it is inhibited by N-nitro-L-Arginine Methyl Esther. A flavonoid was isolated by bioassay-guided purification, and showed moderate cardiovascular activity. Conclusion: The results of the present study lend some support to the popular report for the medicinal use of the flowers of Ch. p. in the control of blood pressure. However, the failure to identify all substances with cardiovascular activity, and the quick loss of life of this plant, can negatively affect the discovery of new drugs. Grant number: UNAM-DGAPAIN221010-2 EVALUATION OF TOTAL PHENOLIC CONTENT AND ANTIOXIDANT ACTIVITY OF MALVA PARVIFLORA L. Marañón Ruiz V.F. Herrera de la Torre J. D. Almanza Orozco R. Miranda Beltrán M. L. Aparicio Fernández X. Chiu Zarate R. División de Estudios de la Biodiversidad e Innovación Tecnológica, Centro Universitario de los Lagos. Universidad de Guadalajara, e-mail: [email protected] In popular culture in the region of the Altos of Jalisco (Lagos de Moreno, Encarnación de Díaz, etc.) used the cooking of the Malva parviflora L, for the treatment of tumors in the womb. Medicinal plants have played an important role in the last five decades in the 1,2 treatment of cancer and many other diseases. New clinical applications of most plant 3 secondary metabolites and their derivatives have been applied to the fight against cancer. Flavonoids have been implicated as responsible for the antioxidant activities of some plants 4 medicinales. Through this study, the principal aim is the isolation and characterization of phyto-compounds active of Malva parviflora L. First were extracted the primary metabolites of the roots with a solvent mixture of water/ethanol. After which the extracts were evaporated and concentrated, and finally were separated by column chromatography. Biomolecules 5 present in the fractions were characterized by thin layer chromatography. The reagents used were FeCl3, Benedict's reagent, reagent Ninhydrin, phenylhydrazine reagent, Jenson´s reagent, NBS and Draguendorff reagent. The results showed positive tests for flavonoids, alkaloids and sugars. The obtained fractions were analyzed for the amount of total phenols 6 using the modified method Folin-Ciocalteau and for antioxidant activity was using the method DPPH. Results showed that the fraction 1 presented high values of total phenols and antioxidant activity (77.6 mg/mL, 89.00 mg/mL respectively). These results are promising as a phyto-pharmaceutical from root of Malva parviflora L. Agradecimiento: COECyTJAL-UDG PS-2009-733. 124 CONTRACTILE CHANGES TO ANGIOTENSIN II IN AORTA AND CORONARY ARTERY IN IN THE GENE MUTANT MICE SGCD (B6.129 SGCDTM1MCN) Marin-Romero MC*, & Castillo-Hernández MC*, Castillo-Henkel C*, Guevara-Balcázar G*, Rosas-Vargas H , Coral,# Vázquez RM* *Departamento de Posgrado e Investigación. Escuela Superior de Medicina, & # IPN. Unidad de Investigación Médica en Genética Humana, IMSSS. CMN 20 de Noviembre, ISSSTE. México, D.F. [email protected] In limb girdle muscular dystrophy and cardiomyopathy are alterations in smooth and cardiac muscles due to the lack of delta sarcoglican. Pathophysiological changes in these disturbances are not precisely known, have suggested the involvement of different systems in this disease such as renin-angiotensin system, this paper aims to examine the role of angiotensin II in this experimental model null mice to delta-SGIn this protocol we use female mice Knock-out and wild type from 5 months old, it were anesthetized with pentobarbital (50 mg/kg IP) and heparine (50 UI), after that we proceeded to dissect the aorta and heart. Both the aorta and heart were placed in an isolated organ system, which keeps krebs solution . and bubbled with carbogen (95% O2 and 5% CO2). Finally we proceeded to make curves -9 -6 concentration response to angiotensin II (10 - 10 ).We obtain significant differences between coronary perfusion pressure and the contractile response to angiotensin II in the mouse mutant versus wild mouse, this response being higher in the mutant mice, suggesting a greater sensitivity in response to angiotensin II in this mouse compared to wild mice TUMORAL MARKERS IN LYMPHOMA INDUCED BY 7,12-DIMETHYLBENZ[A]ANTHRACENE IN RAT AS A MODEL TO STUDY ANTI-TUMOR AGENTS. Laura E. Marquez-Delgado, Claudia A. Reyes-Estrada y Patricia Yahuaca-Mendoza. Programa de Doctorado en Farmacología, U.A. de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, México. E-mail: [email protected] Lymphoma is a malignant process, which now has shown a significant increase in the incidence rate. Therefore studies are essential in experimental models for understanding mechanisms of alteration, particularly marker molecules for early diagnosis and disease monitoring, and so have the tools for research and evaluation of anticancer agents. The aim of this study was to characterize an experimental model of lymphoma induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rats by the presence of tumor markers. Female Wistar rats received DMBA using 3 different schemes (P.O., 5 days a week for several weeks): group 1, 20 mg/kg/day for 6 weeks; group 2, 20 mg/kg/day for 5 weeks; and group 3, 10 mg/kg/day for 6 weeks. Animals were left to evolve during 9, 6 and 6 weeks post-DMBA, respectively. Histopathology and cytotoxicity-tumor markers, such as gamma-glutamyl transpeptidase (-GT) acid phosphatase (AP), carcinoembryonic antigen (CEA), alphafetoprotein (AFP) and lipoperoxidation were measured. Histological examination showed that in group 1, was lymphoma preferentially induced, in addition to metastases, although survival was only 20%. In group 2, lymphoma was found more than breast cancer, increasing survival to 60%. With lower dose of DMBA (group 3), the most common cancer was breast, but the survival was 40%. In all cases, tumor markers were elevated over the control value, higher in lymphoma, as evidenced by the -GT and AP. CEA increased by 15, 13 and 8.5 times, in groups 1, 2 and 3 respectively, while AFP showed the greatest increase in breast cancer (400%). In preliminary studies prednisone and vincristine were administered, and it was noted that prednisone prevented the elevation of CEA. Increased lipoperoxidation in liver and kidney was around 80% and 170% respectively, suggesting a strong association with oxidative stress. This experimental model may be useful tool for the preclinical study of antineoplastic drugs.Project funded by FOMIX CONACYT-ZAC-2009-01-121753 125 MIDAZOLAM INDUCES HISTOLOGICAL ALTERATIONS IN CEREBELLAR CORTEX OF MOUSE FROM P8 TO P15 DAYS OLD María Cristina Márquez-Orozco*, María Verónica Gasca-Ramírez, Graciela de la Fuente-Juárez, Amalia Márquez-Orozco. Embryology Department. Facultad de Medicina, Universidad Nacional Autónoma de México. México D.F. 04510. Email: [email protected] Midazolam (MDZ) is a widely known benczodiazepine minor tranquilizer. It is important in pediatric intensive care and analgesia for newborn babies as well as premature infants as an antiepileptic and anxiolytic drug. We have previously shown that MDZ sc injected in mice from postnatal (P) day P8 to P29 induces histological alterations in cerebellar cortex. The aim of this work was to investigate if MDZ administrated from P8 to P15-days of age induces histological changes in the developing neonatal cerebellar cortex of mice, and if those changes are similar to the ones induced by exposure to MDZ from P8 to P29 days of age. Two pup ICR strain mice groups were sc injected daily from day P8 to P15. The first group (MDZ) with single daily MDZ doses (2.0 mg/kg/bw) and the second group (C) with saline solution. Mice (10 MDZ and 10 C) were killed in a CO2 atmosphere on P16 day; the cerebellum was fixed in 2.5 % glutaraldehyde, post-fixed in OsO4, and embedded in epoxy resin. The semifine sections obtained were stained whit toluidine blue and observed under a comparative light microscope. In the molecular layer of the cerebellar cortex of MDZ group numerous and voluminous cells were observed. A reduced number of cell bodies in Purkinje neurons were observed in the Purkinje cell layer, any ones had shrink cytoplasm, hyperstained, and with degeneration signs. The nucleus showed atypical heterochromatin distribution, and irregular nuclear surface. The dendrite tree showed swelling branches. The cerebellar glomeruli and myelin fibers showed delayed differentiation. The heterochromatin of granular cells showed atypical distribution. These alterations resembled those showed in the cerebellar cortex of mice treated from postnatal P8 to P29 days with MDZ. The results show that postnatal exposure (P8 to P15) to MDZ produces histological changes in the cerebellar cortex similar to those induced by postnatal exposure to MDZ from P8 to P29 days. LONG-LASTING EFFECTS IN ADULT (12 MONTHS OLD) CEREBELLAR CORTEX OF MICE EXPOSED IN UTERO TO DIAZEPAM. Amalia Márquez-Orozco*, Graciela de la Fuente-Juárez, María Verónica Gasca-Ramírez, María Cristina Márquez-Orozco. Embryology Department. Facultad de Medicina, Universidad Nacional Autónoma de México. México D.F. 04510. [email protected] Benzodiazepines (BDZ) are widely used as ansiolytic, and to treat insomnia, muscular spam, stress-related disorder, epilepsy, preoperative preparation, premature activity of the utero, eclamptic and preecalmptic states; in pregnant epileptic women or in those with physiological or psychiatric conditions. The aim of this study was to investigate the changes in fetal mouse cerebellar cortex caused by exposure to DZ during gestation and persisting until the 12th month of age. Two gestating ICR strain mice groups were injected, the first group (DZ) with single daily doses of DZ of 2.7 mg/kg/bw/sc; the second group (C) with saline solution. Offspring's were spontaneously born and wet-nursed by their mothers. Each litter was reduced to 6 males and 2 females. Adult mice (12 months-old) of DZ and C group were killed in CO2 atmosphere, the cerebellum was removed, fixed in 10% formaldehyde or Zamboni fixers, embedded in Paraplast; the sections obtained were stained with H-E and observed under a comparative light microscope. In the cerebellar cortex of DZ group, scare Purkinje cells with a disoriented dendritic tree and an increased number of cells in molecular layer (p<0.05) were observed. Results showed that prenatal exposure to DZ produces in the 12 months-old mice permanent histological alterations in the cerebral cortex. 126 LONG-TERM EFFECTS OF MEDROXYPROGESTERONE ON VASCULAR ALPHA-1 ADRENERGIC RECEPTORS IN FEMALE RAT AORTA DURING HYPERTENSION. Marian 1,3 1 2 E. Martínez-Cruz , Maximiliano Ibarra , J. Javier López-Guerrero , Víctor Manuel Farías1 Rodríguez, Rafael Villalobos-Molina . 1Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, UNAM, Av. de los Barrios 1.Los Reyes Iztacala, Tlalnepantla 54090, México. [email protected]. 2. Departamento de Farmacobiología, CIVESTAV-Sede Sur 3.División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas ―Dr. Ignacio Chávez‖, UMSNH Hormones are one of the most important factors regulating blood pressure in females. The effects of progesterone on cardiovascular system are not totally understood. We investigated the effect of medroxyprogesterone (MPA), a progestin used in the hormone replacement therapy, on vascular alpha-1 adrenergic receptors during hypertension by nitric oxide deficiency in rats. Female mature Wistar rats were subjected to bilateral ovariectomy (OVX rats). Three weeks after surgery animals were randomized to the following treatments: a first group OVX (without treatment); a second OVX+MPA (15 mg/ kg/ week/ 4 weeks); OVX+LN ω (L-NAME, L -N-methyl arginine esther, at a dose 75 mg/ day/ 7 weeks); OVX+LN + MPA and a group same age and weight were used as controls (CTRL rats). Systolic blood pressure (SBP) was measured by a tail-cuff method. After treatments, aortic vessels were isolated and contracted with phenylephrine; in some experiments selective alpha-1 adrenergic receptors antagonists (BMY 7378, cloroethylclonidine and RS100329) were used. The CTRL, OVX and OVX+MPA groups were normotensive along the study; OVX+LN and OVX+LN+MPA were hypertensive until MPA administration started, showing higher SBP. Concentration-response curves to phenylephrine revealed endothelial dysfunction caused by ovariectomy. BMY 7378 and RS100329 showed non-competitive antagonism in aortic rings with endothelium; while in endothelium-denuded rings antagonists showed competitive antagonism mainly in the OVX+LN+MPA group. The pKB value for BMY 7378 (alpha-1D adrenoreceptor antagonist) was higher than that reported (pKB 8.5 vs 8.2); while pKB value for RS100329 (alpha-1A adrenoreceptor antagonist) was lower than that reported (pKB 8.2 vs 9.6). Cloroethylclonidine did not evoke curve displacement in any group. This study revealed that MPA elicits effects on affinity of vascular alpha-1 adrenoreceptors during hypertension in female ovariectomized rats. EFFECT OF TLALTIPIZOL ON UTERINE SMOOTH MUSCLE OF RAT. Martínez- Enríquez ME, García Delgado AJ, Campos-Sepúlveda AE. Departamento de Farmacología, Facultad de Medicina, UNAM, México, DF. 04510. [email protected] In Mexico are used a great variety of plants for treatment of the diabetes and have been carried out studies of some of them in animals, however not all present same effectiveness. The tlaltipìzol is however jicama species that is used for treatment of diabetes in several states of the Mexican Republic, they have not been carried out studies etnomedics that demonstrate the above mentioned. For such a reason the present work is determine the biological activity of tlaltipizol. Segments of 1-2 cm of longitude of uterus of Wistar rats, females, were obtained that were in estro. Tissues placed in chambers for isolated organ, o with De Jalón solution, to 32 C, pH 7.4 and bubbled with carbogen (95% O2 and 5% CO2). The contractile effect was registered for a connected transducer to a polygraph Grass. Dose-8 -4 Response-Curve (DRC) was carried out at 5-HT (1x 10 to1x10 M) alone or in presence of the tlaltipizol juice. The results show that the tlaltipizol decrease the contractile activity of uterine isolated muscle and in presence of 5-HT in the last concentrations, for such a reason we conclude that possibly jicama this acting as antagonist of serotonergic receptors. 127 THE 5-HT7 RECEPTOR-MEDIATED MENINGEAL DILATATION INDUCED BY 5CARBOXAMIDOTRYPTAMINE IN RATS IS NOT ALTERED BY 5-HT DEPLETION AND CHRONIC CORTICOSTERONE TREATMENT E. MARTÍNEZ-GARCÍA, C.SÁNCHEZMALDONADO AND J.A. TERRÓN. Departamento de Farmacología, CINVESTAV-IPN, Apdo. Postal 14-740, Zacatenco 07000, México D.F. Low brain serotonin (5-HT) levels between attacks (possibly promoting receptor sensitization) and high circulating levels of cortisol are remarkable features of migraine. Sensitized 5-HT7 receptors mediating craniovascular dilatation could be the target of massively released 5-HT during migraine headaches1. This work analyzed the effect of chemical lesion of the central 5-HT system and chronic corticosterone (CTC) treatment on dilatory responses induced by the 5-HT1B/1D and 5-HT7 receptor agonist, 5-carboxamidotryptamine (5-CT), in the middle meningeal artery (MMA) of rats. 5-CT-induced meningeal dilatation in rats pretreated with the 5-HT1B/1D receptor antagonist, GR127935, is mediated by 5-HT7 receptors2. Wistar rats were pretreated with desipramine and anesthetized; then, they received an i.c.v. injection of either vehicle (VEH; 1% ascorbic acid) or 5,7-dihydroxytryptamine (5,7-DHT); this treatment drastically decreases brain 5-HT levels.3 Six days later, animals were treated daily with vehicle (Veh; 1 ml/kg, i.p.) or CTC (20 mg/kg, i.p.) for two weeks. Five days after treatments, animals were anesthetized and prepared for recording of blood pressure, i.v. drug administration and measurement of blood flow in the MMA by laserDoppler flowmetry. After stabilization, rats received GR-127935 (1 mg/kg, i.v.) alone or combined with the 5-HT7 receptor antagonist, SB-269970 (1 mg/kg, i.v.); 15 min later, a concentrationresponse (C-R) relationship for the effects of 5-CT (10nM-1mM) on vascular conductance in the MMA was constructed in each group (VEH-Veh, 5,7-DHT-Veh, VEH-CTC and 5,7-DHT-CTC); 5CT was applied topically on the exposed dura mater encephali. 5-CT produced concentrationdependent increases in conductance in all groups; responses did not differ between groups though a trend toward a decrease was evident in 5,7-DHT-pretreated animals. 5-CT responses were similarly blocked by SB-269970. Supported by NIH Grant 5R01TW006622. EXCITATORY ROLE OF THE 5-HT7 RECEPTOR IN THE TRIGEMINOVASCULAR 1 SYSTEM OF THE RAT: RELEVANCE TO MIGRAINE E. MARTÍNEZ-GARCÍA , M. 2 2 1 1 LEOPOLDO , E. LACIVITA AND J.A. TERRÓN . Departamento de Farmacología, 2 CINVESTAV-IPN, Apdo. Postal 14-740, Zacatenco 07000, México D.F.; Universitá degli Studi di Bari, Dipartimento Farmaco-Chimico, via Orabona, 4, 70125 Bari, Italia Serotonin (5-HT) has been implicated in migraine but the nature of its involvement remains unknown. This study analyzed the effect of 5-HT7 receptor activation on c-fos-like immunoreactivity (c-fos-LI) induced by intracisternal (i.c.) capsaicin in the trigeminal nucleus caudalis (Sp5C) and on blood flow in the middle meningeal artery (MMA) of anesthetized rats. Animals received subcutaneous (s.c.) injections of LP-211 (a 5-HT7 agonist; 10 mg/kg), SB656104A (a 5-HT7 antagonist; 3 mg/kg), and SB-656104A (3 mg/kg) + LP-211 (10 mg/kg). After 20-40 min, animals received an i.c. injection of capsaicin (0.1 µM) or its vehicle (100 µl; 20 µl/min for 5 min; both). Two hours later, rats were perfused, and the brains processed for c-fos immunohistochemistry. Other animals were prepared for recording of blood flow in the MMA using a laser-Doppler probe, and blood pressure and heart rate. These variables were measured after local application of LP-211 (0.1 nM-1mM) in animals that had received intravenous (i.v.) vehicle (1 ml/kg), SB-269970 (a 5-HT7 antagonist; 1 mg/kg) or topical CGRP8-37 (a CGRP antagonist; 100 µM). Capsaicin but not its vehicle induced strong c-fos-LI in laminas I and II (LI-II) of Sp5C. LP211 had no effect on c-fos-LI but strongly increased the response to i.c. capsaicin in Sp5C (LI-II); this effect was abolished by SB-656104A; the antagonist also abolished c-fos-LI induced by capsaicin thus suggesting involvement of endogenous 5-HT. LP-211 produced concentrationdependent increases in meningeal blood flow; this response was inhibited by both SB-269970 and CGRP8-37 thus implying involvement of 5-HT7 receptors and CGRP release. The 5-HT7 receptor could be a target for the prophylactic treatment of migraine. Supported by NIH grant R01TW006622. 128 EFFECT OF AURANOFIN ON TAENIA CRASSICEPS CYSTICERCI SURVIVAL AND GSH/GSSG RATIO. Martínez-González, José de Jesús; Miguel Enrique Cuéllar-Mendoza, Omar Huerta-Herrera e Irene Patricia del Arenal Mena. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Apartado Postal 70-159, México 04510, D.F., México Auranofin is a gold-derived salt which has been used in clinic to treat rheumatoid arthritis (Ann Rheum Dis. 1976. 35:251-7); currently, its possible use as anticancer agent is being assessed (Biochem. Pharmacol. 2010. 79:90-101). Since this drug has a high affinity for selenocysteine, it is a potent selenoprotein inhibitor. Thioredoxin glutathione reductase (TGR) is a selenoenzyme that transfers electrons from NADPH to oxidized glutathione (GSSG) and to oxidized thioredoxin. In its reduced form, both substrates are essential for the maintenance of redox homeostasis in cells. TGR has proposed as a pharmacologic target because it is the only enzyme with this function in parasitic platyhelminths (Trends Parasitol. 2004. 20:340-6). The TGR of Taenia crassiceps cysticerci purified to homogeneity is irreversibly inhibited with 10 nM Auranofin (Mol. Biochem. Parasitol. 2004. 133:61-9). In vitro when T. crassiceps cysticerci is exposed to Auranofin a lethal dose-dependent effect is found (Parasitol Res. 2010. 107:227-31), while the 100% of cysticerci population die after 12 h of exposure to a concentration of 10 µM of this drug. In this study the GSH/GSSG ratio was determined and it was observed that auranofin decreases the amount of total glutathione and the GSH/GSSG ratio decreases from 7:1 in basal conditions to 2:1 in cysticerci treated, thus favoring a more oxidative intracellular environment which would promote the death of the parasite. On the other hand, in the case of the cysticercosis model, when this drug was administered to mice infected with cysticerci, the number of cysticerci did not increase in relation to control. This work was supported by research grant PAPIIT IN-220710-3 from Dirección General de Asuntos del Personal Académico, UNAM. EFFECTS OF 17-ETHINYLESTRADIOL AND 17ß-ESTRADIOL ON COAGULATION FACTORS IN MALE WISTAR RAT. Joel D. Martínez Maldonado, Yanira Franco Murillo, Ruth Jaimez Melgoza. Department of Pharmacology, Faculty of Medicine. Universidad Nacional Autónoma de México. The use of estrogens in contraception or in replacement therapy leads to an increased risk of venous thrombosis. In the present study we explored the effect of ethinylestradiol (EE) and 17ß-estradiol (E2) on coagulation screening tests (CST): prothrombin time (PT), activated partial thromboplastin time (aPTT), and coagulation factors (CFVII, CFX, CFXI, and CFXII). Male Wistar rats received subcutaneously different doses of EE or E 2 (1, 3, 10 and 30 mg/kg/sc) during three consecutive days and data were compared with vehicle administered rats (propyleneglycol 0.3ml/sc; V). Plasma samples were obtained from iliac artery under anesthesia and processed with a fibrintimer using appropriate reagents for each determination. EE significantly increased PT and aPTT when compared with V: 8.5, 13, 15, and 10%; and 32, 35, and 28%; (p<0.05), for each drug and dose tested, respectively. In contrast, E2 had no effect on CST. EE significantly diminished the activity of FVII (10, 13, and 10%); FX (10, 9, 15, and 14%), and FXI (15, 17, 19, and 18%), when we compared with V (p<0.05). E2 increased the activity of CFVII (7 % at 1 mg/kg, p<0.05), and CFXI (10, 14, 24, and 24%, p<0.05), but caused a diminution of CFXII (9%; 10 mg/kg). Unlike E2, in our rat model EE had effects on extrinsic, intrinsic and common coagulation pathways. The inhibitory action of EE on CF, observed in these experiments is not consistent with other reports. Future studies are necessary to identify how estrogens regulate the transcription of genes involved on coagulation system. 129 HEPATOPROTECTION AND TUMORAL MARKERS MODULATED BY CRATAEGUS OXYACANTHA ANTIOXIDATIVE EFFECT IN EXPERIMENTAL ALCOHOLIC LIVER CIRRHOSIS. José Luis Martínez-Rodríguez*, Rosalinda Gutiérrez-Hernández y Patricia Yahuaca-Mendoza. Programa de Doctorado en Farmacología, U.A. de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, México. E-mail: [email protected] Alcoholic liver cirrhosis, an irreversible disease, that causes oxidative stress (OxS) as a result of increased reactive oxygen species, whose have been related to the the transition to liver cancer which may be manifested through the presence of early tumor markers (ETM). In order to know whether reducing OxS amending the ETM, we propose the use of antioxidant extract from Crataegus oxyacantha to assess its hepatoprotective effect. In male Wistar rats (200-250 g) was induced alcoholic liver cirrhosis model with ethanol (3 g/kg/day, P.O., for 12 weeks); injury indicators were used to determine alterations on liver function, such as enzyme and cytotoxicity (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and lactic dehydrogenase), metabolic (bilirubin and liver glycogen), histology, lipid peroxidation in liver and measurement of ETM as carcinoembryonic antigen (CEA), αfetoprotein (AFP) and acid phosphatase (AP). In the model of cirrhosis was co-administered extract of C. oxyacantha (100 mg/kg/day for 12 weeks) as a preventive antioxidant. Results showed evidence of alterations in animals who received ethanol. In alcoholic cirrhosis, LPox increased 3.2 times over the control, as well as -GTP and ALT (43% and 164% respectively); bilirubin increased by 4 times over control, while the glycogen storage was depleted up to 17%, alterations which were partially prevented by C. oxyacantha. ETM were increased in liver cirrhosis, compared to control, reaching up to 493% for CEA, 109% for AFP and 38% for AP. C. oxyacantha modified the presence of these ETM, reducing its levels up to 96% for CEA, 75% for AFP and 4% for AP. Besides avoiding the magnitude of damage induced by ethanol, C. oxyacantha prevented the increase in ETM, suggesting an additional benefit by delaying a possible transition from cirrhosis to a tumor condition. Extract of C. oxyacantha is a promising compound for the management of chronic liver damagen * Number 15606 CONACYT Project Fellow. Project funded by Fondo Sectorial SEPCONACYT Ciencia Básica, Code CB-2008-01-105986. BIOETHICAL ANALYSIS OF CLINICAL RESEARCH THAT IS CARRIED OUT BY THE PHARMACEUTICAL INDUSTRY IN MEXICO. Martínez-Rodríguez G, Álvarez MA, CamposSepúlveda AE. Maestría en Bioética, Facultad de Medicina, UNAM; México, D.F., 04510. [email protected] Clinical research is an essential process to support the introduction of new health products, which have to be safe and efficient. Since it involves human subjects, it has to be subject to rigorous and compulsory monitoring using ethical guidelines that safeguard the integrity of the participants. Currently, in clinical research carried out in Mexico, there are ethical deficiencies that jeopardize the rights of participants and even the research itself. Therefore, it is necessary to find the best way to carry out clinical trials to maximize benefits and minimize risks. The rights, safety and well-being of the trial participant are the most important considerations and should prevail over interests of science and society. Through the application of questionnaires to Clinical Research Associates, this paper aims to place, bring out and analyze the most frequent ethical deficiencies in Clinical Research that takes place Mexican pharmaceutical industry. Based on the results it will be possible to reflect on their origins, relevance and possible solution. 130 ANTI-NEOPLASTIC EFFECT OF L-ORNITHINE ANALOGUES "IN VITRO". MedinaEnríquez, Miriam-Marlene*; Velázquez-Ortiz, Indra-Victoria*; Alcántara-Farfán, Verónica*; Aguilar-Faisal, Leopoldo**; Trujillo-Ferrara, José Guadalupe***; Rodríguez-Páez, Lorena I.* *Laboratorio de Enzimología, Depto. Bioquímica, ENCB-IPN; **Laboratorio de Medicina de Conservación, depto. Graduados, ESM-IPN ***Laboratorio de Bioquímica Médica I, Depto. Bioquímica, ESM-IPN. Prol. Carpio y Plan de Ayala s/n, Col. Santo Tomas C.P. 11340 México, D.F. e-mail: [email protected] Polyamines (PAA), putrescine, spermidine and spermine, which are essential for differentiation, growth and cell division, are natural constituents of animal, plants and bacteria cells. The inhibition of PAA synthesis by inhibiting the enzymes that synthesize them has been the logical approach of the strategies for the development of new chemotherapeutic agents against pathological states of cell proliferation. Many inhibitors have been obtained, especially of ornithine decarboxylase because it is the enzyme that regulates the biosynthetic pathway and its inhibition may have optimal therapeutic outcomes. At present, efforts in this field are focused on the development of better inhibitors of the enzymes involved in the metabolism of PAA. The aim of this study was to determine the cytotoxic and antiproliferative effects two L-ornithine analogues, N-δ-trifluoroacetyl-ornithine (NFAO) and N-δ- chloroacetylornithine (NCAO), on neoplastic mammalian cells in culture. The results showed that NCAO caused cytotoxic effects on HeLa cells (cervical carcinoma) and HepG2 cells (human hepatocarcinoma) in a concentration- and time-dependent manner. In addition, the NCAO caused inhibition of proliferation of HeLa cells. The NFAO caused cytotoxic effects on HepG2 cells in a concentration- and time-dependent manner but was less efficient than NCAO. The NFAO did not affect HeLa cells. Control Vero cells were unaffected by both treatments. MEDICAL PRESCRIPTION AND ITS APPLICATION AFTER ESTABLISHING PHARMACOLOGICAL VIGILANCE SYSTEM UNDER THE INTERNAL MEDICINE SPECIALTY HOSPITAL GRAL. "DR. MIGUEL SILVA. * Aída Mejía Sánchez, * Alvaro Rodriguez Barron. * Universidad Michoacana de San Nicolás de Hidalgo, *Hospital General Dr. Miguel Silva SSM, Morelia, Mich. The accurate medical records avoid omissions and incomplete notes and / or mistaken notes, which contributes also to avoid a current problem within the hospitals called Medication Errors (ME). Those ME are often caused because the low quality of the clinical files which means the file does not fulfill the requirements appointed by the NOM-168-SSA-1998. The previous mentioned is also resulting in a poor medical attention to the patient, causing adverse drug reactions or even death and the possibility of lawsuits against people related to the health care. The aim of this study was to identify if there is a difference between registration and implementation of prescription drugs before and after the implementation of a drug monitoring system in the internal medicine specialty, it was developed in two periods with three years of difference between each one; the study was retrospective, descriptive and transversal and was realized in General Hospital "Dr. Miguel Silva "in the city of Morelia Michoacán. It included 107 medical indications from complete clinical records of October 2006 and 99 from January 2009; bearing in mind medicines prescribed but not applied, and applied medicines that were not prescribed as well. Incompatibility was found among the records of clinical prescription and implementation by nursing staff in both studied periods. However, the comparison between the first and the last period shows a significant difference 2 of X (P = <0.0001), therefore is possible to assume that once and after the Pharmacological Vigilance System was introduced the mentioned incompatibility decreased, which suggests that after implementation of drug monitoring system this incompatibility decreased, providing an improved quality of patient care, as demonstrated by some authors in similar studies. Among the drugs involved in these two situations predominated antibiotics, diuretics, NSAIDs and inhibitors of proton pump, also considered as drugs of abuse described in the literature. 131 DL-3-HYDROXY-3-ETHYL-3-PHENYL PROPIONAMIDE (DL-HEPP) POSSIBLE GABAA 1 2 RECEPTOR MODULATOR Meza Toledo Sergio Enrique , Norman G. Bowery 1 Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico 2 Nacional, Prol. Carpio y Plan de Ayala, CP 11340 México D. F, México., Department of Pharmacology, The Medical School, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. The compound DL-HEPP has a broad profile of anticonvulsant activity. It protects mice and rats against seizures induced by pentylenetetrazol, bicuculline, thiosemicarbazide, maximal electroshock, kindling and in the genetic absence epilepsy rats of the Strasbourg model. It also protects against the gamma-aminobutyric acid (GABA) withdrawal syndrome, which shows an extraordinary resistance to the classic antiepileptics. However, the mechanism underlying the action of DL-HEPP is not known. To explore it, we made binding studies using DL-HEPP and a series of phenyl alcohol amides (PAA). DLdid not displace 3H-GABA from GABAA receptors and only weakly displaced 3H-GABA and 3HCGP62349, a GABAB receptor antagonist, from GABAB receptors in rat brain crude synaptic membranes. The electrically (40 mA, 4 Hz for 3.5 min) and potassium chloride (15 mmol/L) evoked 3H-GABA release from rat brain substantia nigra (SN) slices was studied. R-baclofen (10 BAB receptor agonist, produced an inhibition of the electrically evoked 3H-GABA B receptor antagonist, but was not affected by DLalter the electrically evoked 3H-GABA release in the absence of baclofen. The addition of DL-evoked release of 3H-GABA release 3 control, but it was able to significantly reduce the inhibitory effect of GA HGABA release evoked both by electrical and potassium chloride stimulation. In preliminary A receptor antagonists, inhibited the electrically evoked release of 3H-GABA from rat SN slices, and DL-HEPP might act as a negative GABAA receptor modulator in rat brain slices. IMPACT OF THE PHARMACIST IN THE HEALTH TEAM: IMPROVEMENT OF 1 2 PRESCRIPTION FOR DIABETIC AND HYPERTENSIVE PATIENTS. Mino D , Capellá D , 3 4 5 1 2 Reyes H , Jasso L , Doubova SV . Instituto de Geriatría, SSA. Universidad Autónoma de 3 4 5 Barcelona, Instituto Nacional de Salud Pública, Hospital Infantil de México, Instituto Mexicano del Seguro Social. One out of thirteen prescriptions in primary care fail to provide accurate treatment and half are potentially harmful. Reduce the proportion of diabetic and/or hypertensive patients who receive wrong or inadequate prescriptions.Controlled trial study at a Mexican Institute of Social Security family medicine clinic in Mexico City. The intervention introduced a service of "pharmacological recommendations" given by pharmacists. Physicians that allowed access to medical records and prescriptions for their patients with diabetes and/or hypertension were included. Sample size was 56 physicians in order to detect a 25% reduction in the proportion of patients who received prescriptions with errors such as "clinical", "prescription filling" or "both." We included 69 physicians and pharmacists reviewed 161 prescriptions of 160 patients. 49% of patients received prescriptions with at least one error that was detected by pharmacists. In 59% of patients prescriptions showed "clinical" errors, 27% of patients’ prescriptions had "both" errors and 14% of patients received prescriptions that were wrongly filled. "Clinical" errors that prevailed were potential drug-drug interactions (D-DI), while most common error in "filling prescriptions" was ―lack of information in the range of administration". For "both" errors "lack of information in the range of administration‖ and potential D-DI were most common. In 43% of the revised prescriptions 132 errors were recorded. Most frequent drug groups were non-steroidal anti-inflammatory drugs, vitamins, antibiotics and lipid lowering. Only 19% of patients the physician corrected their prescriptions before they were delivered. Conclusion: The impact of the intervention was less than expected, however, it is necessary to improve the strategy and implement other actions to improve physician´s prescriptions and consequently reduce the risk of patients. 132 CHEMICAL AND HISTOPATHOLOGIC ANALYSIS OF THE EFFECT OF THE MIXTURE 1 OF SEVEN PLANTS (EHAM7) IN A MODEL OF EXPERIMENTAL CIRRHOSIS Miranda 1 1 1 2 Beltrán M.L*; Soria Fregozo C, Gutiérrez Coronado O, Rosales Muñoz C.G.; López 2 1 Velázquez A. L; Treviño Ortiz R y Huacuja Ruiz L. [email protected] Laboratorio de Aplicaciones Biomédicas. Centro Universitario de los Lagos, Universidad de Guadalajara, 2 Instituto de Enfermedades Crónico Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No 850, Col Independencia, 43100, 3 Guadalajara, Jalisco, México Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas, Universidad de Guadalajara, Introduction. Popular Medicine have reported a variety of medicinal plants used in gastrointestinal diseases. Objective. Demonstrate the hepatoprotective effect of a mixture of seven plants (EHAM7) through liver and lipid profile, and histology in a model of experimental cirrhosis in rats. Methodology The EHAM7 was obtained from the mixture of 7 plants: (Bidens odorata (Aceitilla), Tecoma stans (Tronadora), Linum usitatissimum (Linaza), Cynara scolymus (Alcachofa), Equisetum hyemale (Cola de Caballo), Peumus boldus (Boldo) y Rosmarinus officinalis L (Romero). Groups of control rats and cirrhotic rats treated with and without the EHAM7, at 200 mg / kg for eight weeks. Subsequently, animals were sacrificed to assess serum lipid profile and hepatic, and liver histologic studies. Results. The levels of ALT, AST, BD and BT were observed increased while the PT and ALB decreased in cirrhotic rats, compared to other groups. Compared to the levels of TG, CHOL, LDL and HDL showed a decrease in cirrhotic rats compared with cirrhotic rats treated with EHAM7 whose levels were very similar to the control group. Histological analysis showed: cytoarchitecture preserved, much like those found in cirrhotic rats treated with the mixture and control, whereas in cirrhotic rats were observed: total distortion of the parenchyma and fibrous tissue bands. Conclusion. The EHAM7 has hepatoprotective effect in cirrhotic rats, possibly because it has polyphenolic compounds with antioxidant activity. PRIMARY AND SECONDARY HIDATIDOSIS BY Echinococcus granulosus, MODULATION OF THE CELLULAR ATMOSPHERE TO REMAIN BY LONG SEASONS OF 1 TIME, A CHALLENGE FOR THE THERAPEUTIC ONE. Mondragón de la Peña MC , 2 3 3 2 Blancas Mosqueda M , Leandro Alvarez RD , Orta García ST , Tavizón García JP . 1)Doctorado en Farmacología UAMHyCS, UAZ. 2)Lab de Biología de la Conservación UACB, UAZ. 3)UACQ UAZ. The hidatidic illness is caused for the metacestode de Echicoccus. In order to understand this, they have been used different models. In new studies BALB/c mice like proposal were used to evaluate the ILEchinococcus granulosus. In the present study BALB/c mice were infected by IP whit PSC of E. granulosus route, the mice were sacrificed and the hidatidic cysts in liver were observed the 16 weeks postinfection, the liver was analyzed by histopathology and a fraction of these was taken for the total extraction of ARN for amplification (RT-PCR) with primers for IL-6, TNF TGF and GADPH. The expression in situ of these cytokines was shown by FISH (fluorescence in situ hybridization). The expression of IL-6 and TNF declined four weeks progressively later. The inflammatory cytokines were expressed normally in animal no infected. Our results suggest E. granulosus induces a probably site immunosuppression by TGF , this seems to be a mechanism of evasion of the immune response of the host. In a second study, hepatic samples of pig infected with E. granulosus were used, Where evaluated the hepatic immune response by means of the expression in situ of cytokines pro (IL-6, TNF and anti-inflammatory (IL-10, TGF .The total RNA of hepatic sections was extracted, which were used for amplification with RT-PCR with primers of IL-6, TNF , IL-10, TGF and G3PDH. It was observed a pattern similar to found in the model murine, an increase in the expression of the anti-inflammatory and a decrement of the pro-inflammatory cytokines probably indicating a suppression of the host using the parasite all these resources to remain by long period of time in the host. 133 ANALYSIS OF THE EXPRESSION OF CYTOCHROME P450 IN THE SKELETAL 1 1 STRIATED MUSCLE. Dora Molina-Ortiz , Araceli Vences-Mejía , Rafael Camacho2 1 1 2 Carranza , José González- Zamora , Oscar Colín-Martínez , Javier Espinosa-Aguirre . 1. National Institute of Pediatrics. 2. Biomedical Research Institute UNAM. Mexico City, Mexico. The cytochrome P450 enzymes (CYP) catalyze the metabolism of a wide variety of endogenous and exogenous compounds. CYP are mainly expressed in the liver and extrahepatic tissues. Recently, overexpression of the CYPs in neoplastic has been shown, leading to an exacerbated metabolism causing the inactivation of antineoplastic agents and therefore chemoresistance. The rhabdomyosarcoma (RM) is a childhood neoplasm of the striated muscle of high prevalence in Mexico and strongly chemoresistant. Current therapy for RM includes anticancer drugs cocktails with inevitable side effects. The modulation of the expression of the CYP enzymes is unknown in both in the healthy striated muscle, as well as in the RM. The comparison of the CYP expression patterns in both tissues will allow for proposing better treatment schemes for RM using cancer chemotherapeutic drugs that are not inactivated by the CYP found in the tumor. Objective: Assess the genetic expression of CYP1A1, 1A2, 3A4, 3A5, 1B1, 2E1 and 2W1 in the healthy skeletal striated muscle. Methodology: Using real-time RT-PCR, different CYP were analyzed from 17 samples of healthy striated muscle from children of different ages. Results: The CT results from each of the genes analyzed showed that both CYP1B1 (X of Ct=30.72), as well as CYP2E1 (X of Ct=30.68) are constitutively expressed in the striated muscle at all the ages considered. On the other hand, no genetic expression of CYP2W1 was detected in any of the samples. The rest of the genes had a diverse pattern of expression unrelated to gender or age. Conclusions: The skeletal striated muscle possesses the genetic expression of diverse CYPs that if correlated with its protein expression, could lead us to consider it as a tissue of important metabolic capacity. The results of the expression of the CYPs in the healthy muscle are the basis for later comparison with RM. FUNCTIONAL ALTERATIONS ON THE CONTRACTILE RESPONSE IN THE GUINEA-PIG ILEUM INDUCED BY SEVERAL PERIODS OF HYPOXIA AND ISCHEMIA IN-VITRO. Montes de Oca Mejorada Misael, González Cabañas Janeth, Gómez Acevedo Claudia, Santiago Mejía Jacinto, Ventura-Martínez Rosa. Departamento de Farmacología. Facultad de Medicina. UNAM. This study examines the alterations on the contractile response in the guinea-pig ileum induced by hypoxia and ischemia in-vitro. Six segments of 2.5-cm long of the whole ileum were obtained from each guinea pig. They were mounted in a 30 ml organ-bath containing Krebs-Bicarbonate solution maintained at 37°C and constantly bubbled with the mixture of O2 and CO2. The resting tension was fixed at 1 g. The preparations were allowed to equilibrate for 60 min under continuous superfusion (10 ml/min). In one group of experiments, hypoxia was induced by oxygen deprivation replacing the oxygen by a mixture of 95%N2-5%CO2 for 10, 20 and 40 minutes in different preparations. In other group of experiments, ischemia was induced by oxygen deprivation and glucose-free solution for the same periods of time. Thereafter, oxygenation was restored in all tissues and were subjected to chemical stimulation with ACh (1X10 -9 to 1X10-5 M), KCl (3.2X10-2 M) and electric stimulation (14 V, 0.3 Hz, 3 ms). Hypoxia in vitro decreased significantly the reactivity of the guinea-pig ileum to ACh and electrical stimulation resulted in approximate 28% and 77% (10 min); 21% and 32% (20 min); and, 63% and 80 % (40 min) decrease in the contractile response. Contractile responses to KCl from hypoxic preparations were not significantly alterated. On the other hand, ischemia in vitro decreased significantly the reactivity of the guineapig ileum only to Ach, but not to KCl and electrical stimulation. These results suggest that hypoxia followed for reperfusion induced more alterations than ischemia in vitro. The contractile responses in hypoxic tissues to neurogenic stimulation decrease to a significantly greater extent than the non-nerve mediated responses of the intestinal smooth muscle. This study was supported by PAPIIT (grant IN201809-3). 134 NEUROPHARMACOLOGICAL PROFILE AND TOXICITY OF ETHANOLIC EXTRACT OF Rhodiola rosea L. Montiel-Ruiz R.M., Roa-Coria J.E., Patiño-Camacho S.I., Déciga-Campos M. Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina del I.P.N., D.F., México. Rhodiola rosea is a popular medicinal plant commonly used in folk medicine in Europe and Asia as an adaptogen due to its ability to increase an organism’s resistance to physical, chemical and biological stress. The present study was conducted to evaluate the neuropharmacological profile and toxicity of R. rosea. An ethanolic extract of the roots of R. rosea (56-316 mg/kg, p.o.) was administered in mice; exploratory activity, anti-anxiety, sodium pentobarbital-induced hypnosis and pentylenetetrazole-induced seizures were tested, clonazepan was used as positive control. The results in the experimentals models tested showed: a significant reduction of the exploratory behavior and in the number of rearing. R. rosea did not modify the sedative-hypnotic and anticonvulsant response with respect to vehicle. R. rosea was not toxic in Artemia saline and in mice. In addition, R. rosea was not genotoxic in the micronucleus assay. The present results confirm some preclinical and clinical studies indicating stimulating and anxiolitic-like effects of R. rosea with a very low risk of toxicity. MODIFICATION OF PLASMA BIOMARKERS AND IMAGING OF MILD COGNITIVE 1,2 IMPAIRMENT IN ELDERLY BY GINKGO BILOBA Navarro Pineda Darinel Uribe 1 2 3 Hernández Alejandro , Olivares Corichi Ivonne María , Jiménez Zamarripa Carlos Alberto , 1 2 1 Londaíz Gómez Roberto , Calzada Mendoza Claudia Camelia . Hospital Central de PEMEX 2 3 Lab. 107 de la SEPI de la ESM-IPN Hospital Psiquiátrico ―Dr. Samuel Ramírez Moreno‖, SAP-SS Mild cognitive impairment (MCI) is a stage between the cognitive impairment in normal aging and demential illness, without functional disability. So far there are different drug therapies for dementia; of which, one of the present drugs is the Ginkgo biloba (Gb) that acts as a neuroprotective by blocking the apoptosis, at level cerebral cortex, but which have not been described in detail in Mexican patients its effects on different risk factors related to the DCL. So in this study we examined the effect of Gb on plasma biomarkers and imaging in elderly with MCI. The study is experimental (by the administration Gb for 4 months), compared to placebo, single-blind and pilot preliminar pilot. We Included elderly over 70 years old diagnosed with MCI. The variables analyzed at 0 and 4 months after treatment were: a) oxidative stress (OE): damage to lipids and proteins, and antioxidant defenses, b) metabolic syndrome (MS): diabetes, hypertension, dyslipidemia, central obesity and insulin resistance, c) tomographic analysis: cortical atrophy, and cerebral atherosclerosis. Before of treatment, we found that patients had a higher severity of MS and insulin resistance compared with the national average; additionally, they had a lower educational level. After treatment with GB showed increased cognitive ability (higher scores on neuropsychological testing), while there was a decrease of the memory areas affected in both groups. With regard to MS and EO parameters, we did not find differences statistical In conclusion, this study has shown improved global cognition GB without having a positive effect on memory. On the other hand Gb does not reduce EO and SM; the previous findings makes the search necessary of new molecular routes of action, besides increasing the size of sample to make a representative analysis. 135 EFFECT OF CAPTOPRIL AND LOSARTAN ON THE EARLY ALTERATIONS OF 1 1 1 DIABETIC NEPHROPATHY. Núñez-Ortiz A.R , Vázquez-Cruz B , Segura-Cobos D , Amato1 2 1 2 Martínez D , López-Sánchez P Farmacología, UIICSE, FES Iztacala UNAM, Sección de graduados, ESM, IPN. [email protected] Diabetic nephropathy (DN) is the first cause of terminal renal disease. DN involves a group of micro and macro-vascular injuries; characterized by functional (glomerular hyper-filtration) and structural (renal hypertrophy (RH)) alterations. The cause of these alterations it’s not clear. However, it was reported that renin angiotensin system (RAS) it’s related on development of DN, this because angiotensin-converting enzyme inhibitors and AT 1 antagonists are highly effective in slowing the progression of renal disease. Objective: Study the activity of losartan (LOS) and captopril (CAP) on early alterations of diabetic nephropathy. Methods: 36 male rats between 230-250 g were randomly divided into a diabetic model group -1 that received an injection of 65 mg kg streptozotocin (STZ) with sodium citrate buffer as vehicle and control group with only the vehicle. Two days after STZ, when we observe clinical symptoms of DM, diabetic and control rats were divided into 3 groups: No treatment group, -1 treatment with LOS and treatment with CAP (10mg K ) during a week. After that time, kidneys were removed and renal functional and morphological parameters were measured. Results: 48 h after STZ administration rats present hyperglycemia, polyphagia, polydipsia, polyuria and weight loss. Proteinuria was decrease in both treatments (LOS 26.7 µg/24h and CAP 31.5 µg/24h) respect with control group (42.5 µg/24h). Kidney weight was high in diabetic rats. Proteins/DNA quotients in control group were 0.09 u.a. and in diabetic group were 0.11 u.a. Conclusion: A week after STZ administration, rats develop RH. However, when organisms receive inhibitor of AT1 receptor, some alterations on renal damage were decreased. These results confirm the role of RAS on DN. Supported by PAPIIT IN210307. SEX DIFFERENCES IN EXPERIMENTAL ANXIETY IN MIDDLE-AGED RATS: EFFECTS OF DIAZEPAM. Olvera Hernández S, Fernández Guasti A. Departamento de Farmacobiologia, Cinvestav, México DF Anxiety disorders are the most prevalent psychiatric illnesses and there is a sexual dimorphism in their incidence, with women outnumbering men. Aging in rodents is similar to aging in humans, in the female rat after 10 months of age there is an increase in the incidence of animals showing irregular cycles. Finally, the female rat enters a state of aciclicity with the loss of reproductive function. In males from 12 months of age onwards there is a reduction in the serum levels of testosterone. These changes are analogous to the periods of perimenopause and menopause in women and partial androgen deficiency in men. The defensive burying behavior model is used for the study of experimental anxiety. Two of the measured parameters are the burying behavior latency, which inversely reflects reactivity, and the cumulative burying, which directly reflects the level of experimental anxiety. We studied the influence of sex and endocrine milieu and it response to diazepam using Wistar rats with an age range of 11-14 months. Females were selected in two endocrine conditions: irregular cycles and persistent diestrus. Middle aged males were also included. Because burying implies motor coordination, a rotarod and spontaneous ambulation tests were done. We observed that under basal conditions the burying behavior latency was higher in males than in females, while cumulative burying was higher in the two groups of females compared with males. In both groups of females diazepam administration (0.5, 1.0 mg/kg) produced an increase in burying behavior latency. The cumulative burying time was not reduced in any group after any diazepam dose. In the group of persistent diestrus, 1 mg/kg of diazepam caused a decreased motor coordination. These data suggest that diazepam in middle aged subjects impairs reactivity but lacks an anxiolytic-like action. 136 EFFECT OF THE COMPOUND LQM319 AND CAPTOPRIL IN THE CONTRACTION PRODUCED BY ANGIOTENSIN I AND ANGIOTENSIN II IN THE PRESENCE OF 1 ANGIOTENSIN 1-7 IN AORTAS FROM SPONTANEOUS HYPERTENSIVE RATS. Orozco 1 1 Cortes Nancy Verónica, Hernández Valencia Ignacio, Martínez Aguilar Luisa Laboratory Myocardial Pharmacology, FES-Cuautitlán-UNAM Introduction: In our laboratory we evaluate antihypertensive activity of drugs of Mexican origin. The compounds have shown to be effective. Objective: To compare the effect of the compound 4-tert-butyl-2 6-bis (thiomorpholino-4-ylmethyl) phenol with Captopril in muscle contraction induced by Ang I and Ang II in the presence and absence of Ang-1-7 in aortic rings. Methods: The rats were treated with either the compound or Captopril with a dose of 1 mg / kg i.m./5 days. Aortic rings were mounted in isolated organ chambers under conditions established and with an inhibitor of NO synthase. Concentration-Response curves to Ang I -10 -6 and Ang II of 10 -10 M in the presence and absence of angiotensin 1-7 were obtained. This was carried out for both compound and captopril groups. Maximal contraction data were recorded. Results: The cumulative concentration-response curves were obtained for Ang I and Ang II. It was observed that both the compound LQM319 and Captopril had a similar vasorelaxant effect, although when the aorta rings were incubated with Ang-1-7, the contraction decreased even more. Conclusions: In this study we demonstrated that vasodilation was independent of nitric oxide since NO synthase was inhibited. In addition we found that the compound 4-tert-butyl-2,6-bis (thiomorpholino-4-ylmethyl) phenol had vasorelaxant effects similar to captopril. PAPIIT IN224310-3, GVC-20 OMNIALVA SOFTWARE AND BIOMEDICAL RESEARCH EQUIPMENT. ORTEGAMARTINEZ N, HERNÁNDEZ-ALVA A, OMNIALVA M.R, MEXICO. Omnialva is a Mexican trademark, dedicates to software’s development and equipment for biomedical research. We have more than six years on market; we have presence on several Mexican Health Institutes, Hospitals and Universities. Including some foreigner customers. Our mission: To give a custom solution to the researcher, giving an easy way to make their work. We count with a engineer team able to adapt space, electronics and software to the specifics research’s requirements. Omnialva’s systems are the result of several years of development and multidisciplinary integration. Some of our systems are: system for study of cicardian rhythm, equipment for open field test ,wheels for forced locomotion and our OASPADVid system based on video, which lets record the subject's activity using a video camera, in this equipment the researcher can define the area of study and another interesting zones. Then, the OASPADVid processes the image and gives: trajectory, covered distance, and the time stayed in the interest zone. If you need electronic devices to sense any process, or to automate your experiments and recordings, also if you need software for data acquisition or process control or well, to apply statistics analysis on your data base and show the results, OMNIALVA will design a custom solution to you. 137 PHYCOBILIPROTEINS AND C-PHYCOCYANIN OF Spirulina maxima PROTECT AGAINST HgCl2-CAUSED OXIDATIVE STRESS AND CELLULAR DAMAGE IN THE KIDNEY. Ortiz-Butrón R., Blas-Valdivia V., Rodríguez-Sánchez R., and Cano-Europa E. Laboratorio de Neurobiología. Departamento de Fisiología de la Escuela Nacional de Ciencias Biológicas-IPN. México, D.F. [email protected] The kidneys are the primary target organ where mercury is absorbed, accumulated, and expresses its toxicity. Cyanobacteria of the genus Spirulina were used to prevent oxidative stress and cellular damage in different toxicological models. Our objective was to study if the phycobiliproteins of Spirulina maxima protect renal cells against mercury-caused oxidative stress and cellular damage in the kidney. We used 48 male mice that were assigned into eight groups; the control group received 100 mM phosphate buffer (PB) ig and 0.9% saline ip; PB + 5 mg/kg ip HgCl2; PB plus 100 mg/kg ig phycobiliproteins or C-phycocyanin, and the other groups receiving HgCl2 + 50 or 100 mg/kg ig phycobiliproteins or C-phycocyanin. The administration of the phycobiliproteins, C-phycocyanin or PB was made 30 min before saline or HgCl2 for 5 days. Mice were killed by cervical dislocation and the left kidneys were used to determine lipid peroxidation, quantification of reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized (GSSG) content. The right kidneys were processed for histology. Our results demonstrated that HgCl2 causes oxidative stress and cellular damage. All doses of phycobiliproteins and C-phycocyanin prevent enhancement of oxidative markers and partially protect against HgCl2-caused cellular damage. Funded by grants from the SIP 20090485 and 20110336. RESVERATROL INCREASE ANTI-INFLAMMATORY AND ANALGESIC EFFECTS OF 2 1 2 DICLOFENAC IN RAT. Ortiz-Padilla SA. , Medina-Sifuentes AM. , Aguirre Bañuelos P. 1 2 Facultad de Medicina de la Universidad Autónoma de Aguascalientes Facultad de Ciencias Químicas de la Universidad Autónoma de San Luis Potosí. Resveratrol is an herbal and protective compound produced by the red grapes, which has been used for various purposes. Resveratrol has been shown many effects over health in humans and animals; some of which are an analgesic and anti-inflammatory effect. In this study analgesic and anti-inflammatory effect of resveratrol alone and in combination with diclofenac was demonstrated. For this propose a carrageenan-induced inflammation and hyperlagesia carrageenan-induced models were used in rats. We observed that 25 mg/Kg of resveratrol not increase analgesic and anti-inflammatory of diclofenac (100 mg/Kg), but 50 and 100 mg/Kg of resveratrol significantly increase both analgesic and anti-inflammatory of diclofenac (100 mg/Kg) in rats. These results suggest that the combination of resveratrol and diclofenac could be used as a drug combination of choice for the treatment of inflammatory diseases that occur with pain. 138 ASSESSMENT ETHANOLIC EXTRACT OF CALEA URTICIFOLIA MILL DC ON BLOOD 1 GLUCOSE AND LIPIDS IN HEALTHY RATS FED A HIGH FAT DIET. Ortiz-Segura, M.C. 2 1 and E. García-Chávez Programa Multidisciplinario de Posgrado en Ciencias Ambientales, 2 UASLP Instituto de Investigación de Zonas Desérticas, UASLP Type 2 diabetes mellitus is one of the main causes of death worldwide and its incidence is rising. It has been shown that life-style factors, such as increased fat intake and reduced physical activity, are associated with obesity, insulin resistance and may lead to diabetes. In Mexico more than 300 plant species have popular use in the treatment o this disease. Extracts from Calea urticiolia (Miller) DC, known as ―negrito‖ in the village Potrero del Carnero, Rayon, S.L.P., are used to treat inflammation and diabetes. Establish the effects of an ethanolic extract of C. urticifolia (EECU) on glucose and lipid metabolism in high-fat-fed rats. Male Wistar rats weighing 100-120 g were fed with standard chow (SC) or a high fat diet (HFD) for 16 weeks. Blood samples were collected from the tail vein every four weeks during this period. After that, rats were divided into four groups, one group of each diet was administered water or EECU (0.88 mg/kg) for 8 weeks. Blood samples were obtained every two weeks. Blood glucose, cholesterol and triglycerides levels were measured. HFD induced an increase in blood glucose after eight weeks. Blood cholesterol and triglycerides not increased significantly after 16 weeks. EECU administration reduced blood glucose levels significantly. Changes in blood cholesterol and triglycerides were no observed. EECU has hypoglycemic effect in hyperglycemic high-fat-fed rats. EFFECT OF CACAO DERIVED (-)-EPICATECHIN ON MITOCHONDRIAL SWELLING 1 INDUCED BY MYOCARDIAL ISCHEMIA/REPERFUSION INJURY IN RATS. Ortiz Vilchis, 1 1,2 2 1 Rubio Gayosso, Guillermo Ceballos and Francisco Villarreal Escuela Superior de 2 Medicina del Instituto Politecnico Nacional, Mexico City, Mexico; and University of California, San Diego, California ([email protected], [email protected]) Evidence shows that a diet rich in flavonoids significantly decrease the incidence of cardiovascular diseases mainly due to their antioxidant, vasodilator, antithrombotic and antiinflammatory properties. Flavonoids are found in many types of fruit and vegetables. Consumption of cacao and derivatives like dark chocolate has been proposed as cardioprotective reducing cardiovascular morbi-mortality. (-)-Epicatechin (EPI) is the most abundant flavonoid in cacao and it has been proposed has responsible of cacao effects. However, the mechanism(s) by which (-)-epicatechin exerts its effects remains unclear. On the other hand, previous papers show that cardiovascular diseases trigger mitochondrial alterations. Myocardial ischemia/reperfusion induces alterations in cellular calcium homeostasis and intracellular pH and increase the production of reactive oxygen species. These alterations promote mitochondrial permeability transition pore opening (mPTP) resulting in water and ions diffusion into the mitochondrial matrix triggering mitochondrial swelling and proapoptosis signals. In this study, we analyze the effects of EPI on mitochondrial swelling induced by calcium in isolated mitochondria from healthy and ischemia/reperfusion (45 min ischemia and posterior reperfusion) rat hearts. Results show that EPI, in a concentration dependent manner [0.01µM - 0.1mM], decreases mitochondrial swelling. (-)-Epicatechin treatment (1 mg/kg/day during 10 days by gavage) significantly inhibits swelling in mitochondria isolated from ischemia/reperfusion hearts. Together, these results strongly suggest that EPI protect mitochondria against damage conditions induced by calcium or ischemia/reperfusion injury. 139 EFFECT OF URSODEOXYCHOLIC ACID ON OXIDATIVE STRESS AND SGLT2 1 1 EXPRESSION IN THE KIDNEY OF DIABETIC RATS. Horacio Osorio , Israel Coronel , 1 1 2 1 1 Abraham Arellano , Martha Franco , Bruno Escalante and Rocío Bautista . Department of 2 Nephrology, Instituto Nacional de Cardiología ―Ignacio Chávez‖ México City, 14080. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV)Monterrey. 66600. Monterrey, Nuevo León, México. There is increasing evidence during diabetes increase oxidative stress and cellular transport of glucose. These alterations play an important role in the development and progression of diabetic nephropathy. Aims: The purpose of this work was to study the effect of ursodeoxycholic acid (UDCA) on the oxidative stress and sodium-glucose cotransporter (SGLT2) expression in the kidney of diabetic rats. Methods: Diabetes was induced by streptozotocin 50 mg/kg, i.p. UDCA (40 mg/kg) was administered p.o. daily from the first to the 30 day after the diabetes was confirmed. At 30 days the kidney was obtained and cortex and medulla were dissected. Oxidative stress was measured by catalase (CAT), super oxide dismutase (SOD) and glutathione peroxidase (GPx) activity in cortex and medulla. SGLT2 expression was evaluated in cortex. Results: At day 30, diabetic animals showed hyperglycaemia, lower body weight, glycosuria, diuresis. In cortex and medulla from diabetic rats, decrease CAT activity and GPX activity increase. No significant change was observed in the SOD activity in the cortex or medulla from diabetic rats. SGLT2 expression increase in diabetic compared with control rats. UDCA treatment decreased hyperglycaemia and increase body weight. In the cortex and medulla of diabetic rats the UDCAtreatment increase CAT activity. Furthermore, UDCA treatment also resulted in a significant decrease in GPX activity and SGLT2 expression. Conclusions: In conclusion, the present study showed that UDCA treatment prevented the oxidative stress in kidney from diabetic rats. Furthermore the results suggest that UDCA treatment modulate SGLT2 expression. PHARMACOLOGICAL EVALUATION OF FL-6, AN IMMUNOMODULATORY DRUG, IN 1 CHRONIC HEPATITIS INDUCED IN WISTAR RATS Ulises Osuna Martínez , Vera Lucia 2 3 1 Petricevich Lopez , Rogelio Hernández Pando , Jorge Reyes Esparza , Lourdes Rodríguez 1 1 Fragoso Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, 2 Cuernavaca, México, Facultad de Medicina, Universidad Autónoma del Estado de Morelos, 3 Cuernavaca, México, Departamento de Patología, Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán, Ciudad de México, México Actually there are different treatments for chronic hepatitis that has different side-effects in the patients, the research of new drugs for these diseases is necessary. The aim of this study was to evaluate the pharmacological effect of FL-6, a new immunomodulatory drug, in a chronic hepatitis induced immunologically in rat by porcine-serum (PS) administration. 32 Wistar rats (150 g) were used and divided into 4 experimental groups (n=8): 1. Control (PBS 0.5 ml 3-times per week for 8 weeks), 2. FL-6 (50 ng/kg 3-times per week for the last 4 weeks), 3. Hepatitis (PS 373 mg/kg twice per week for 8 weeks), 4. Hepatitis + FL-6 (doses mentioned above). At the end of the 8th week of the protocol, rats were sacrificed using CO2 chamber. Biochemical markers of liver function (ALT, AST, ALP and GGT), inflammatory marker (IL-6) and anti-inflammatory marker (IL-10) levels were evaluated in serum samples; in liver tissue determinations of GSH was done. Animals with hepatitis had an increase in ALT (1.53-fold), AST (1.18-fold), ALP (1.78-fold) and GGT (3.43-fold) levels in comparison with control group (P<0.05). Rats with hepatitis and treatment with FL-6 had a reduction of ALT (49.28%) and AST (39.44%) levels as compared with hepatitis group (p<0.05). Rats with hepatitis developed an increase in IL-6 (1.6-fold) and IL-10 (6.1-fold) levels as compared with control group (p<0.05). In rats with hepatitis and treatment with FL-6 we observed a reduction in IL-6 (24%) level as compared with liver fibrosis group (p<0.05). The levels of GSH in hepatitis group was 74.8% less in comparison of control group (p<0.05); the treatment with FL-6 in presence of hepatitis had no changes on GSH levels. In conclusion, the treatment with FL-6 reduced biochemical parameters (ALT and AST) and inflammatory marker (IL-6) in rats with chronic hepatitis induced by PS administration. 140 CHANGES DURING DEVELOPMENT IN THE TRANSIENT KINETICS OF THE 1 REACTIVITY OF RAT AORTA TO PHENYLEPHRINE. Javier Padilla-Pérez , Carlos 1 1 1 Castillo-Henkel , Ma. Carmen Castillo-Hernández Escuela Superior de Medicina del Instituto Politécnico Nacional SEPI, Av Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomas, México, D.F., 11340. There is age-related change in the responses to phenylephrine (PE, agonist α1) mediated by adrenergic receptors (AR) α1 in the aorta (Ao) of the rat that is related to changes that can vary with the (thoracic , Tx, abdominal, Ab) region of the vessel. The traditional protocol takes the magnitude of responses at a given time (steady state) and not the rate of change per second (kinetics) of the time course of the transient response (kinetic) protocol to determine the number of distinct phases, which provides a unique insight in terms of time constant (τ in s) underlying the mechanisms of the transient of response, which can not be obtained by examining the steady state. Based on a mathematical model of 3 exponential components and 10 kinetic parameters (3C, 10P) we analyzed transient possible kinetic changes of force development (F, g) induced by PE (10-6 M) in terms of τ and MeanResponseTime (in s ) in Ao of prepubertal rat (P: 70 to <170 g TotalBodyMass; 6 W eeks of Age, n = 9Tx, 9Ab), young adult rat (A: 200-250 gTBM, 8 WA, n = 9Tx, 10Ab) and old rat (O: 230-280 gTBM, 16-18 WA, n = 9Tx, 9Ab). The 3C, 10P identified a rapid phase (Φ1F), a moderately fast phase (Φ2F) and an slow phase (Φ3F). The two-way ANOVA showed a different kinetics (P <0.05: Φ1F τ <Φ2F τ <Φ2F τ) intragroup Ao segment; τ1: Tx and Ab were {A (14.00 ± 1.07) and P (13.31 ± 1.10)}> τ1_O(8.18±1.10); τ2: Tx(97.51± 2.51)> Ab(42.75±2.47) and τ2: P>A>O; and also τ3: Tx(289.87±3.79)> Ab(234.61± 3.73) except from O, and τ3: P>A>O as well. Finally, MRT: Tx(127.44±7.71)>Ab(95.28± 7.58). We concluded that the Ao age-on_transient kinetics of isometric contraction PE induced becomes faster, especially in the Ab segment compared to the Tx one. NEURODEVELOPMENTAL DISORDERS IN ALZHEIMER'S DISEASE. REPORT OF 1 1 5 CASES Palacios-Escalona Sergio , Manzanarez-Colin Mariel Carolina , Villeda-Hernández 2 1 2 Juana , Totxo-Guerrero Daniel Sebastián , Peralta-Rodríguez Brenda , Noemí Gelista 3 4 3 5 Herrera , Sandra Orozco , Luisa Rocha , Castañeda-González Carlos , Horacio Reza 5 2 5 Garduño Treviño Rembao-Bojórquez Daniel , Tristán-Agundis Ma. Francisca . 1.Universidad Nacional Autónoma de México, 2.-Instituto Nacional de Neurología y Neurocirugía ―Manuel Velasco Suárez‖, 3.-CINVESTAV, 4.-CMN SXXI, 5.-Hospital Psiquiátrico 'Fray Bernardino Álvarez' Alzheimer's disease (AD) is the most common cause of dementia in the elderly. It is characterized by progressive loss of higher mental functions, especially memory as well as other disorders aphasia, apraxia and agnosia. Currently there are an estimated 18 million cases worldwide. In the next 30 years it is expected that two-thirds of dementia cases reside in developing countries. The EA can be your family (earlyonset) or sporadic (lateonset). At the histological level is characterized by the presence of neuriticplaques, neurofibrillary tangles, synaptic degeneration and neurona ldeath. At molecular level levels of βamyloid and tauprotein are indicative ofthis condition.Wedescribe the histopathological andneurodevelopmental disorders in 5 cases autopsy diagnosedwith Alzheimer's disease.5 cases were selected from both sexesin hospital Fray Bernardino Alvarez and INNN "MVS" with an age range between 40 and 78 years. We reviewed the clinical history and the tissues were cut, stained for histology and immunohistochemistry and examined under Leica photomicroscope. In all cases, cerebral atrophy wasfound in two arteriosclerosis, atthemicroscopic level neuritic plaques andextensive neuronal migration failure, neurofibrillarytangles, cortical dysplasia and some neurons bifurcated, as wellas changes secondary to hypoxia, staining for nestin was positive indicating immature or developingneurons. White matter was found with neuritic plaques (heterotopya) and demyelination of nerve fibers. The results agree with the bibliography. Besides shown not only degenerative but also neurodevelopmental disorders that indicates mal formation of the CNS. That result is also observed in neuroimage studies. 141 ANTI-HELICOBACTER PYLORI AND GASTROPROTECTIVE ACTIVITIES OF AQUEOUS EXTRACT OF CUPHEA AEQUIPETALA (LYTHRACEAE). Juan Francisco Palaciosa a b b a* a Espinosa , Guillermo García-Valencia , Robert Bye , Edelmira Linares , and Irma Romero Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de b México, Ciudad Universitaria, C.P. 04510, México, D.F., México. Jardín Botánico, Instituto de Biología, Universidad Nacional Autónoma de México, Ciudad Universitaria, C.P. 04510, México, D.F., México. Helicobacter pylori is a spiral, Gram negative and microaerophilic bacterium strongly related with chronic gastritis, duodenal and gastric ulcer, adenocarcinoma and gastric MALT lymphoma. The emergence of antibiotic-resistant strains has developed a great interest in searching for alternative therapies for the treatment of infection and their related-diseases. In this study, we evaluated the in vitro anti-Helicobacter pylori activity of the aqueous extract of Cuphea aequipetala (CAI), a species widely used in the Mexican traditional medicine system to treat stomach ailments like gastritis. Additionally, we evaluated the gastroprotective effect using an ethanol-induced gastric ulcer model, and acute toxicity, both in mice. Results showed that CAI, in agar and broth dilution methods, presented minimum inhibitory concentrations of 125 significantly reduced by oral administration of CAI in a dose-dependent pattern. Finally, the LD50 was estimated up than 5 g/kg. In conclusion these data indicate that C. aequipetala possess gastroprotective and anti-H. pylori compounds that could be related with its etnomedical efficacy, and did not show acute toxicological effects making it a promising native herb for an integral therapy, alone or in combined therapies, in the treatment of patients with gastric ulcer caused by this bacterium. This work was partially supported by DGAPA-UNAM (IN 225711-3). CYSTICIDAL ACTIVITY OF EXTRACTS FROM SOME PLANTS USED AS 1 ANTIPARASITIC PLANTS IN THE FOLK MEDICINE Palomares Alonso Francisca , Rojas 1,6 2 3 Tomé Susana , Juárez Rocha Victorino , Rufino González Yadira , Palencia Hernández 4 1,5 1 Guadalupe , Jung Cook Helgi . Laboratorio de Neuropsicofarmacología, Instituto Nacional 2 de Neurología y Neurocirugía. Universidad Autónoma Metropolitana, Xochimilco. 3 4 Laboratorio de Parasitología, Instituto Nacional de Pediatría. Laboratorio de 5 Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía. Facultad de Química, 6 UNAM. Facultad de Ciencia y Tecnología, Universidad Simón Bolívar, México, DF. In the search of new therapeutic alternatives for neurocysticercosis treatment, the aim of the present study was to evaluate the cysticidal activity of 5 plants used in the mexican traditional medicine as antiparasitic: Tagetes lucida (pericón), Teloxys graveolens (epazote de zorrillo), Lippia graveolens (orégano), Jatropha dioica (sangre de drago) y Prunus serotina (capulín). The hexane, ethyl acetate and methanolic extracts were obtained by maceration of dried plant material. The in vitro cysticidal activity was performed using Taenia crassiceps cysts and albendazol sulphoxide as reference drug. Also, the brine shrimp lethality test was carry out as preliminary assay to select the active extracts. The plant extracts were evaluated in the concentration range from 1 to 200 µg/mL. The results of lethality assay for A. salina showed that the most active extracts were: methanolic from capulín and pericón; ethyl acetate from epazote and sangre de drago, and the hexanic from orégano. All of these extracts, exhibited cysticidal activity, being the extract from capulín the most active with a EC50 value of 17.2 µg/mL. The CE50 values of epazote, pericón, orégano and sangre de drago were 44.3, 47.8, 65.4 y 68.8 µg/mL respectively. The results of the present study revealed the cysticidal potential of these plants and their research should be continued in order to identify the active compounds as a basis for the development of novel cysticidal drugs. 142 SYNERGISTIC ANTINOCICEPTION BETWEEN LYSINE CLONIXINATE AND MORPHINE IN THE RAT FORMALIN TEST. Palomino-González G., Pérez-Urizar J., Aguirre-Bañuelos P. Facultad de Ciencias Químicas de la Universidad Autónoma de San Luis Potosí. México. The combination of analgesic drugs is a common practice in the clinic management of pain. Preclinical studies are needed to determine the usefulness of new drug combinations as well as the nature and magnitude of the interaction. In this study we demonstrated that lysine clonixinate -LC- (anti-inflammatory non steroidal agent) is able to synergize the antinociceptive response of morphine -M- (opioid agent) in the formalin test. 50 μL of 3% formalin was applied to the right hindpaw of male Wistar rats and reduction in flinching behavior was targeted as the antinociceptive effect. Both analgesic drugs reduced the nociceptive response in a dose-dependent fashion during phase 1 and phase 2 of the formalin test (M: 2-4 mg/kg i.m.; LC: 25-150 mg/kg i.m.). Moreover, the mixture of agents at a fixed-proportion (M:LC, 1:29) produced a ED30 (0.6 ± 0.17 mg/kg i.p.) significantly lower to that theoretically predicted (26.3 ± 0.17 mg/kg i.p.). Naloxone (10 mg/kg p.o.) did not reverse the antinociception of lysine clonixinate in any phases, but reverses completely the antinociception of morphine, and partially that of the combination with LC in both phases suggesting a role of the opioid receptor in the synergistic effect of M-LC. These results suggest that sparing morphine with lysine clonixinate would offer a useful tool for the management of moderate to severe acute pain. STUDY OF 2,4-DIMETHOXYNNAMIC ACID AS A POSSIBLE HYPOCHOLESTEROLEMIANT AGENT. Pastor O., Santiago J., Wong C. Laboratorios de Enzimología y Diagnóstico Molecular, ENCB-IPN. E-mail: [email protected] Hypercholesterolemia is a main risk factor in the development of cardiovascular diseases, which are the number one cause of death worldwide. α-asarone has been isolated from multiple natural sources, and it has powerful hypocholesterolemic activity by binding to hepatic 3-hydroxy-3-methylglutaryl-CoA reductase blocking cholesterol biosynthesis. However, due its high toxicity α-asarone has been dismissed as a potential treatment for hypercholesterolemia. Nevertheless, it has been demonstrated that some α-asarone metabolites have hypolipemiant activity and are less toxic than α-asarone. Methylated αasarone metabolites have been evaluated as hypocholesterolemic agents. In this study, we assayed one α-asarone metbolite; the 2,4-dimethoxycinnamic acid (DMC) on wistar hipercholesterolemic rat model under treatment with DMC. To validate the hypocholesterlemic model, we compared it with normocholesterolemic wistar rats. After 7 days of treatment, DMC decreased serum levels of total cholesterol and triglycerides of 29.86% and 53.92% respectively compared with those presented by hypercholesterolemic rats (p<0.05). On the other hand, there was no significant difference in cholesterol elimination, which was determinate by bile flow speed and cholesterol bile levels. Based on the obtained results, we conclude that 2,4-dimethoxycinnamic acid is a lipid-lowering property molecule, because it was capable to decrease serum cholesterol and triglycerides in rats on high lipid diet. In addition, the mechanism of action of DMC seems not to involve the hepaticbile system, since no significant changes in the bile parameters analyzed. 143 ANTIOXIDANT EFFECT OF THE METHANOLIC EXTRACT OF BUDDLEJA CORDATA IN + 1 THE RAT MPP MODEL OF PARKINSON’S DISEASE. Pérez Barrón Gabriela Alejandra , 2 3 2 3 García Bores Ana María , Rubio Osornio Moisés , Ávila Guillermo , Montes Sergio , Ríos 3 1 1 Castañeda Camilo , Monroy Noyola Antonio . Laboratorio de Neuroprotección, Facultad de 2 Farmacia, UAEM, Cuernavaca, Morelos Laboratorio de Fitoquímica, Unidad de Biología, 3 UBIPRO, UNAM, FES Iztacala Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, México, D.F. Parkinson’s disease is characterized by the irreversible loss of dopaminergic neurons in the nigrostriatal pathway. It has been proposed environmental causes through molecules such as the 1-methyl-4-phenylpyridinium (MPP+) that induced oxidative stress. The methanolic extract of plants of the gender Buddleja has been reported to has in vitro and in vivo antioxidant properties protecting of the neuronal death. In the present study were investigated the neuroprotective effect of the methanolic extract of Buddleja cordata in rat MPP+-model. Male Wistar rats (220-250 g of weight) were used. The first day the animals were administered orally with different doses of methanolic extract of B. cordata; 50, 100 and 200 mg/kg or Tween 20 (5% w/v). The fifteenth day, the rats were infused with a single intrastriatal stereotaxic microinjection of MPP + (8 µL) or sterile saline. Six days after the animals were treated with apomorphine (1 mg/kg subcutaneously) and then ipsilateral rotations were recorded during 1 hour. Finally, twenty four hours after the animals were sacrificed by decapitation and lesioned striatum was dissected to dopamine quantification using HPLC with electrochemical detection. The animals administered orally with the doses of 50 and 100 mg/kg showed a significant decrease (p< 0.05) of ipsilateral rotations of 75% (85 turns) compared to control group (170 turns). This neuroprotection was corroborated with dopamine levels in both groups. These preliminary results will be reinforced by analysis of lipid peroxidation. PHARMACOKINETICS OF LIDOCAINE AND ITS METABOLITE AS HEPATIC FUNCTION 1 1,2 3 MARKER IN DOG. BE Pérez-Guillé , F Villegas-Alvarez , A Toledo-López , MA Jiménez1 1 4 4,5 Bravo , JF González-Zamora , MC Carrasco-Portugal , FJ. Flores-Murrieta , RE Soriano1 Rosales . 1) Laboratorio de Cirugía Experimental, Instituto Nacional de Pediatría, 2) Facultad de Medicina, Universidad Nacional Autónoma de México 3) Laboratorio de Farmacología, Instituto Nacional de Pediatría, 4) Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias 5) Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional. Hepatic metabolic function is very important for detection of liver failure and to treat it. Several tests have been widely used to characterize the integrity of liver; however, they do not evaluate the metabolic function of the organ. Several tests have been reported for evaluation of such function; however, most of them require taking several blood samples. Aim: The purpose of this study was to establish if ratio of lidocaine metabolite (MEGX) divided by lidocaine concentration 30 minutes after intravenous lidocaine administration is a good marker of metabolic activity of the liver. Material and method: Nine healthy and two partially hepatectomized and autotransplanted dogs were included in the study. A single 1.5 mg/kg intravenous dose of lidocaine and serum samples were obtained at selected times for 150 minutes. Serum concentrations of lidocaine and MEGX were determined by a validated high-performance liquid chromatographic method. Pharmacokinetic parameters were obtained by non-compartmental methods and ratio of AUC of MEGX divided by AUC of lidocaine was determined for each dog. This ratio was correlated with the ratio of the concentration of the compounds obtained 30 minutes after drug administration. Discussion: A good concordance was obtained, suggesting that ratio obtained with a single sample may be useful to predict the hepatic metabolism function. To validate the test, dogs hepatectomized and autotransplanted were plotted and the results obtained were within the values obtained in healthy dogs. These results seem to indicate that ratio of MEGX/lidocaine obtained 30 minutes after administration could be a good marker of hepatic metabolic function. 144 FLAXSEED OIL SUPPLEMENT TO SPONTANEOUSLY HYPERTENSIVE RATS (SHR) WITH DIABETES: EFFECT ON BLOOD GLUCOSE, BLOOD PRESSURE, CHOLESTEROL AND TRIGLYCERIDES. Pérez-Hernández, I.H. y Mejía-Zepeda, R. UNAM. FES Iztacala. Unidad de biomedicina Lab-7. Av. de los Barrios # 1. Los Reyes Iztacala. Tlalnepantla, Edo. de Méx. C.P. 54090. Tel 5623-1333 ext 39795. e-mail: [email protected] Diabetes and hypertension are main causes of morbidity and mortality in the World. It has been suggested that omega-3 fatty acids ingestion has beneficial effects in controlling various diseases, including diabetes and hypertension. In this work we studied the effect of a flaxseed oil (FO) supplement (rich in omega-3) on glycemia, systolic blood pressure, cholesterol and triglycerides in spontaneously hypertensive rats (SHR) with diabetes.Diabetes was induced in male 48 h newborn SHR with stroptozotocin (STZ). Daily administration of FO since the first month of age, regulated blood glucose at 96 mg/dl, similar to control SHR (78 mg/dl) at the age of 3 months, remaining constant up to 6 months of age (84 and 80 mg/dl respectively). Diabetic rats without FO, had glucose levels between 180 and 220 mg/dl at the same ages. Diabetic SHR showed higher levels of systolic blood pressure since the first month of age, reaching values of 210 mmHg at 6 months-old. In SHR supplemented with FO there was a delayed development of hypertension with systolic blood pressure barely over 140 mmHG. During development of diabetes and hypertension, cholesterol and blood triglycerides concentrations increased at 6 months of age; however, in SHR with STZ and supplemented FO, cholesterol and triglycerides concentrations tend to be normal, or even lower, at 6 months-old.Project supported by PAPIIT IN228610-3 PHARMACOLOGICAL MODULATION OF THE RENIN-ANGIOTENSIN SYSTEM BY a, MATHEMATICAL MODELING Pérez Rosas Norma Citlalcue Rodríguez González Jesús a a G . Unidad Monterrey, CINVESTAV-IPN, Vía del Conocimiento 201, Parque de Investigación e Innovación Tecnológica, Autopista al Aeropuerto km 9.5, 66600, Apodaca NL, México The renin-angiotensin system (RAS) is the most important system in blood pressure homeostasis and pathogenesis of cardiovascular-renal diseases and pharmacology. When blood volume is low, juxtaglomerular cells in the kidneys secrete renin. Renin stimulates the production of angiotensin I (Ang I), which is then converted to angiotensin II (Ang II). Angiotensin II causes blood vessels to constrict, resulting in increased blood pressure. If the renin angiotensin system is too active, blood pressure will be too high. Most hypotensive drugs are designed to block this system in different points. For instance, exist renin inhibitors (RIs) or angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin II receptor blockers (ARBs). We constructed a mathematical model of the RAS, to emulate the response of the reninangiotensin system in human. This model consists in a set of ordinary differential equations. Special attention is paid to the estimation of all the model parameters from reported experimental data. The model equations are numerically solved. These equations allow to model hypertensive and normotensive patients and pharmacotherapeutics. In this study, we show dose-response curves of blood pressure and biochemical components of the renin-angiotensin system. 145 ANALGESIC EFFICACY OF TRAMADOL PLUS LYSINE CLONIXINATE VERSUS TRAMADOL ALONE IN POST-SURGICAL DENTAL PAIN: A RANDOMIZED 1 2 3 CONTROLLED TRIAL. J. Pérez-Urizar , I. Torres-Roque , A. Pozos-Guillén , R. Martínez3 4 4 1 Rider , G. Aguilera-Suárez , M. Gómez-Sánchez . Facultad de Ciencias Químicas-UASLP, 2 San Luis Potosí, México; Dixpertia Investigación Biofarmacéutica y Farmacológica, S.C., 3 San Luis Potosí, México, Facultad de Estomatología-UASLP, San Luis Potosí, México; 4 Farmacéuticos Rayere, S.A., México. The development of new pharmacological strategies such as balanced analgesia allows clinicians to have therapeutic alternatives for relief the treatment of acute pain. In this prospective, doubleblind, randomized, parallel-group and multiple doses clinical trial we evaluated the analgesic effect, as well as the tolerability of a new solid formulation containing lysine clonixinate and tramadol (CLT; 125 + 25 mg po c/8 h) compared to single tramadol (TMD, 50 mg po c/8 h) in patients suffering moderate to severe acute pain following the extraction of two impacted third molars. 40 subjects were allocated into two groups (n=20) to receive the first dose of analgesics treatment when anesthetic effect was ended or the pain intensity was sufficient to patient ask for analgesia into a 6 h period after surgery. Test treatments were evaluated for a period of 96 hours with visual-analogue scale of 10 cm, as well as verbal assessment of 4-point scales. Primary endpoint was defined as the cumulative analgesic effect over time within 0-96 h. Results showed that indicators cumulative analgesic effect 0-96 h (development of pain + analgesic effect), 4-24 h (postoperative analgesia in clinic) and 6-96 h (ambulatory analgesic effect), the time of beginning of significant analgesic effect as well as the therapeutic failure rate (CLT did not exhibited any case) and the overall evaluation of the therapy by patient up to 96 h showed superiority for the CLT combination (50% of the patients felt that it was an excellent therapy against 10% with TMD). Rate of adverse effects of CLT tended to be smaller than the TMD. Taken together, the results of this study suggest that the analgesic efficacy of CLT is superior to that of standard dose of tramadol for relieving acute dental pain, but also that pain relief is more rapidly achieved, with an improved profile of tolerability. PRECLINICAL BASIS FOR THE DEVELOPMENT OF A NEW ANALGESIC 1 COMBINATION: TRAMADOL PLUS LYSINE CLONIXINATE. J. Pérez-Urizar , I. Torres2 1 2 Roque , E. Dibildox-Alvarado , A. Torres-Roque , A. Escobedo-Moratilla, G. Aguilera3 3 1 Suárez , M. Gómez-Sánchez . Facultad de Ciencias Químicas, Universidad Autónoma de 2 San Luis Potosí, México; Dixpertia Investigación Biofarmacéutica y Farmacológica, S.C., 3 San Luis Potosí, México; Farmacéuticos Rayere, S.A., México. The rationale of balanced analgesia is to provide pain relief through additive or synergistic effects, using different analgesics, with a concomitant reduction of side-effects owing to the resulting lower doses of individual drugs and differences in side-effect profiles. The combination of Tramadol (T) with Lysine Clonixinate (CL) has been designed with the goal of obtaining improved analgesia with two drugs acting with different mechanism from action, time of beginning and duration of the effect. In order to evaluate the analgesic potential of CL plus T (CL-T), protocols using experimental visceral and somatic pain models were performed and isobolographic analysis demonstrated that CL-T in a 5:1 fixed-proportion (ED50: CL, 3.6 mg/kg i.p. + T, 0.71 mg/kg i.p. equal to 4.1 mg/kg of mixture) derived in a synergistic response. Such an improved analgesic effect of CL-T was equivalent to standard dose of morphine (0.44 mg/kg i.p.) and superior to ketorolac (0.1 and 1.0 mg/kg) for overcoming the intense-acute nociception in the tail-flick and formaline experimental models in terms of magnitude and duration. The acute highest doses of CL-T (8.2 mg/kg po.) did not differ to vehicle-control when it was acutely given in the ethanolinduced gastric damage model in rats. In addition the repeated administration during 1 week of CL-T (8.2 mg/kg po. t.i.d.) did not produce more gastrointestinal ulcer lesions than observed with control. Finally neither respiratory depression nor intestinal transit-time alteration were observed after the treatment with CL-T. All these findings support that CL-T combination in a 5:1 ratio would represent an adequate alternative in the treatment of severe acute pain. 146 PERINATAL FOOD DEPRIVATION INTERFERES WITH THE MATERNAL AGGRESSION PATTERN AND NADPH-DIAPHORASE POSITIVE NEURONS OF THE LACTATING RAT. 1 2 3 1 Pérez-Torrero, Esther , Margarita I Hernández-Urbiola , Silva-Barrón Carlos I . Depto de Posgrado e Investigación Facultad de Ingeniería, Universidad Autónoma de Querétaro. 2 3 Posgrado en Investigación Biomédica Universidad Autónoma de México. Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro. Maternal aggression of lactating dams is component of the maternal behavioral repertoire, in association with the rearing and protection of the litter, suggesting that the neural circuitry underlying the behavior is activated temporarily. Food deprivation early in life produces permanent, morphological, biochemical and behavioral alterations that may provoke long-term damage. The current study investigates the effects produced by food deprivation on the maternal aggression response (MAR) directed to an intruder, and effects of NADPH-diaphorase (NADPH-d) positive neurons, as indirect evidence of nitric oxide (NO) synthesis, in supraoptic (SON) and paraventricular (PVN) nuclei. The two groups of dams tested for MAR were: Control females (C) came from pups fed normally throughout the study, the undernourished females (U), was obtained from pregnant dams prenatally feeding with 50% of the normal diet (Purina chow) from G6 to G12 and with 60% of the same diet from G13 until G21. After birth, these pups were fed by interchanging a pair of normally lactating mothers every 12 h. After weaning, pups had free access to water and food. The MAR was evaluated on postpartum days 1, 4 and 8. After that fixed coronal sections (40 μ) of SON and PVN were processed for histochemistry positivity with the NADPH-d technique. Data showed significant (p<0.05) statistical differences, being for U dams reduction in the frequency of sniffing, increase of lateral attacks on days 4 and 8, also showed decrease of frontal attacks at day 8. Results also showed increase in the number of NADPH-d positive neurons in U group. Food deprivation may be associated with changes of NO synthesis on neuronal structures implicated in maternal aggression adjustment. Findings underlying neuronal plasticity, and provides evidence that different temporal windows of vulnerability determine the severity of food restriction. Supported by CONACyT Grant No. 91211 (EPT). ANALYSIS OF THE RELAXANT EFFECT OF ROSUVASTATIN LACTONE IN RAT AORTIC RINGS. 1,2 1,3 4 Polanco-Ponce Ana C. , López-Canales Jorge S. Pérez-Álvarez Víctor M. , Castillo 1 1 1 Henkel Enrique , P. López-Sanchez , Castillo-Hernández María del Carmen , Castillo1 1 Henkel Carlos Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina, I.P.N. Plan de San Luis y Díaz Mirón, Col. Casco de Sto. Tomas, México-11340, 2 3 México, D.F. Laboratorios Astra Zéneca, México Instituto Nacional de Perinatología 4 ―ISIDRO ESPINOZA DE LOS REYES‖ Centro de investigación y estudios avanzados (CINVESTAV), unidad zacatenco. México, D.F. The relaxant effect of the lactone of rosuvastatin was evaluated on aortic rings from male Wistar rats (250-300 g) with and without endothelium precontracted with 1.0 µM phenylephrine. The lactone presented a greater potency than rosuvastatin in relaxing aortic rings, with log IC 50 values of -6.88 and -6.07 M, respectively . Unlike rosuvastatin, the effect of its lactone was endotheliumindependent. Pretreatment with either 10 µM indomethacin or 1 mM mevalonate did not inhibit the relaxant effect of the lactone. Nω-nitro-L-arginine methyl ester (L-NAME, 10 µM), the selective nitric oxide-2 (NO-2) inhibitor 1400 W (10 µM), tetraethylammonium (TEA, 10 mM) partially inhibited the relaxant effect of the lactone on endothelium-denuded aortic rings. However, cycloheximide (10 µM) or the combination of TEA plus L-NAME completely inhibited the relaxant effect. Inducible nitric oxide synthase (NOS-2) was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with lactone treated rings. In conclusion, whereas rosuvastatin was associated with a relaxant effect dependent on endothelium and hydroxymethylglutaryl coenzyme A reductase in rat aorta, the lactone of rosuvastatin exhibited an endothelium- and hydroxymethylglutaryl coenzyme A reductase-independent relaxant effect. Both nitric oxide produced by NOS-2 and K+ channels are involved in the relaxant effect of the lactone of rosuvastatin. 147 USE OF GENTAMICIN USING PHARMACOKINETICS PARAMETERS Quiñonez P.Gilberto. Department of Pharmacology and Biophysics, CISALUD Valle Las Palmas, UABC Gentamicin belongs to the aminoglycosides whose common use is for the management of infections with gram negative its therapeutic range is narrow and can lead to significant toxic effects. It is bactericidal to have the ability to penetrate the membrane and synergistic with some Penicillin’s. This work presents an alternate form of safer and more effective dosage. Aim: Assess pharmacotherapy with gentamicin in prospectively in hospitalized patients and perform the individualization of dose based on the determination of levels of serum and the adjustment of dose and therapeutic interval using the kinetic method of Fuller-Goldman. Methodology: The study was developed in the facilities of the hospital Issstecali Tijuana and Tecate involving hospitalized patients. The design of the study was prospective, analytical cuasiexperimental involving patients in the areas of internal medicine, surgery, and ginecobstetrics. Renal assessment is carried out through the determination of urea/creatinine and the implementation of the nomograph of Cockcroft-Gault. The manage 80 mg gentamicin as a continuous infusion for 30 minutos. se a sample 30 minutes post infusion and the other 5 minutes before the next dose. Measured plasma concentrations by a method of EMIT. Result and discussion: The study is carried out in 14 adult patients, 11 female and 3 male. Is a relationship between the volume of distribution and the doses obtained using the kinetic method of Fuller - Goldman and a classical kinetic method of equations. There is a concordance of dose when the kinetic parameter of volume of distribution is 12 to 16.38 L/Kg, the difference of 0.9 to 7.5 mg dose varies in both methods. Carried out an analysis of variance between the obtained dose and the dose between the kinetic method of FG and the kinetics equations did not found any statistical difference, the value of significance was 0.05 Conclusions: The method of Fuller-Goldman presents a huge advantage for the design of safe individualized dosing regimens. It allows us to analyze and readjustment a dose in effective and analytical way. It is an excellent guide for the design of individual dosing regimens and no longer empirically. The predictive power is very acceptable for drugs with a narrow therapeutic window and where the volume of distribution oscillates between 12 and 16.3 L/Kg. CHARACTERIZATION OF RENAL NITRIC OXIDE AND REACTIVE OXYGEN SPECIES 1 2 PRODUCTION IN OBESE MICE. Ramírez Alejandra , Vargas-Robles Hilda , Escalante 1 1 1 2 Bruno , Ríos Amelia * CINVESTAV MONTERREY, Apodaca, N.L., CINVESTAV I.P.N. Departamento de Biomedicina Molecular, México D.F. We have demonstrated in experimental models of chronic kidney disease (CKD) that nitric oxide (NO) renal synthesis decrease is associated with decline in renal function and is accompanied by increase in oxidative stress as result of increased reactive oxygen species (ROS) production and decreased antioxidant enzyme capacity in the kidney. In obesity, kidney function changes are similar to CKD. Therefore it is possible that CKD development may be potentiated in obesity through changes in both NO and ROS signaling molecules. CKD was induced by 5/6 nephrectomy (NFX) in control and obese mice and NO and ROS alterations were assessed. In situ production of NO was evaluated using the oxidative fluorescence dye DAF-2. Confocal images analysis in arbitrary units (arb. unit) of fluorescence showed that a high fat diet in mice diminished NO production as dramatically as NFX. Results are as follow: Control sham 8.5 (n=5 ± SEM), Control NFX 5.2 (n=6 ± SEM), Obese sham 5.3 (n=3 ± SEM), Obese NFX 4.3 (n=3±SEM). Additionally, we sort out three different ranges of calibers in the arteries and found that arteries with the range of 31DHE showed basal florescence in Control Sham mice while a significant increase was observed in the other three conditions. In conclusion we suggest that obesity decreases NO renal vascular production through ROS generation sensitizing kidney for the development of renal failure. Further investigation is needed to identify functional and structural changes that may lead to define and ultimately prevent obesity-related renal injury. 148 PHARMACOKINETIC INTERACTION OF VINCRISTINE AND PREDNISONE IN MURINE MODEL. Claudia Araceli Reyes-Estrada* and Patricia Yahuaca-Mendoza. Programa de Doctorado en Farmacología, U.A. de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, México. E-mail: [email protected] y [email protected] This study evaluated the pharmacokinetic interaction of Vincristine (VCR) and Prednisone PD), antineoplastic and glucocorticoid respectively, widely used in various treatment regimens. In this condition, deleterious effects were assessed in liver and kidney in addition to the pharmacokinetic behavior of VCR in the presence of PD. Female Wistar rats (300 ± 5 g) were divided into 4 groups (n= 10 ± 2 rats per group): control, VCR (0.5 mg/kg, IV), PD (1.6 mg/kg, PO, daily for 15 days), and VCR + PD (similar schemes). Pharmacokinetic samples were taken during 24 h after administration of VCR at different times within the range, for each subject, with a maximum of 5 samples per animal, to quantify VCR by HPLC. At 24 h rats were sacrificed and sampled liver, kidney and blood for determine markers of oxidative stress (hepatic and renal lipid peroxidation), metabolic (bilirubin, urea and liver glycogen) and enzyme activity of gamma-glutamyl transpeptidase and alanine aminotransferase (-GTP and ALT). Indicators of injury, increased in the presence of VCR, which were prevented with prior exposure to PD. Moreover, the pharmacokinetic parameters showed that the volume of distribution of VCR fell from 0,056 L/kg to 0,037 L/kg, while clearance increased from 0.0143 to 0.0996 Lkg-1h-1 when coadministered with PD, which would result in a decrease in average bioavailability, measured as the area under the curve (55.9 vs 26.2 µghml-1). Overall, the results of this study support the use of PD in combination with VCR because it avoids the presence of toxic changes induced by VCR, in addition to modifying the pharmacokinetic behavior of anti-cancer, making it faster. * Number 189891 CONACYT Fellow; Project funded by SEP-PIFOP 2002-33-04 and FOMIX CONACYT-ZAC-2009-01-121753 PPADS, A P2X RECEPTOR ANTAGONIST, AS A NOVEL INHIBITOR OF THE REVERSE + 2+ MODE OF THE NA /CA EXCHANGER IN GUINEA PIG AIRWAY SMOOTH MUSCLE. 1 1 1 2 3 Reyes-García J , Flores-Soto E , Cruz Valderrama JE , Sommer B , Barajas- López C , 1 1 Montaño LM . Depto. de Farmacología, Facultad de Medicina, Universidad Nacional 2 Autónoma de México. DF. Departamento de Investigación en Hiperreactividad Bronquial, 3 Instituto Nacional de Enfermedades Respiratorias, México DF, México. División de Biología Molecular, IPICYT, San Luis Potosí, SLP, México. The Na+/Ca2+exchanger (NCX) is a plasmatic membrane protein. Its principal function is to take 1 Ca2+ out of the cytoplasm and introduce 3 Na+. The increase of the cytoplasmic Na+ concentration, induces the NCX to change to its reverse mode (NCX REV), favoring the Ca2+ entrance. NCXREV can be inhibited by several drugs: 1) KB-R7943 a non-specific compound that blocks voltage dependent Ca2+ channels and store operated Ca2+ channels; 2) SEA0400 that is selective for NCXREV, but difficult to obtain and 3) SN-6. We found that PPADS, known as a P2X receptor antagonist, acts like a NCXREV blocker in guinea pig tracheal myocytes. In freshly dissociated cells, we characterized the NCXREV by substituting NaCl and NaHCO3 by LiCl in Krebs adjust to pH 7.4, and this resulted in the increase of the intracellular Ca 2+ concentration ([Ca2+]i). We analyzed 2 consecutive responses of the NCXREV after 10 min, finding a 94% re-establishment of the initial response. To evaluate the effect of different NCXREV blockers, concentration response curves to PPADS (1, 3.2, 10 and 30 μM), KB-R7943 (1, 3.2 and 10 μM), and SN-6 (3.2, 10 and 30 μM) were constructed. KB-R7943 and PPADS almost abolished NCXREV, although the former was more effective and SN-6 was only efficient at the highest concentration used. Functional studies in organ baths, showed that KCl (60 mM) induced contraction was blocked by D600 and KB-R7943 (around 80%, in a time dependent fashion), but not by PPADS. KCl induced [Ca 2+]i increment in myocytes and this response was significantly decreased (46%) when KBR-7943 (10 μM) was present. Our results demonstrate that PPADS can be used as a reliable pharmacological tool in the inhibition of the NCXREV, with the advantage that it does not block L-Type Ca2+ channels as KB-R7943 does. Supported by CONACYT # 81409 and PAPIIT, UNAM # IN201810-3. 149 SEARCH IMMUNOGENIC EPÍTOPES OF NEURAMINIDASE FROM A H1N1 INFLUENZA a1 a3 A BY COMPUTATIONAL TOOLS. Reyes Loyola Paola Kinara , Correa Basurto Jose, b c c Miguel Quiliano Meza, Verónica Briz, Mª Angeles Muñoz-Fernández, Luis Esteban a2 b a Tolentino López , Mirko Peralta Zimic , Laboratorio de Modelado Molecular y a3 Bioinformática de la Escuela Superior de Medicina, Instituto Politécnico Nacional b c Bioinformatics Unit Faculty of Science and Philosophy Universidad Peruana Laboratorio de Inmunobiología Molecular, Hospital Universitario, Madrid, España In silico experimentation of H1N1 neuraminidase (NA) search for highly immunogenic and conserved epitopes, could decreased financial investment, human resources and time for vaccine design.In this work we have focused to search the best immunogenic epitopes of NA from influenza A H1N1 virus employing the Mexican sequences for the rational design of vaccines, was achieved. Thus is due to the existing vaccines are not enough effective to prevent and control of epidemiological events, as has been demonstrated throughout history, as well as presenting events temporally associated with vaccination.Furthermore, we performed the search and multiple alignment analysis of protein sequences of the neuraminidase (NA) 2009 H1N1 strains of Mexico, being found on October 2010 182 protein sequences which only 119 are fully, then homology modeling for three-dimensional structure (3D) protein sequences of 28 representative strains, 1 wild type and 27 mutants, with 1-5 mutations. Then, the 28 representative strains were subjected to sequence and structural predictors of peptides to complex of major histocompatibility complex type II (MHC II), peptides continues, and peptides-cel B, peptides discontinues. Thus yield search a peptide named here as peptide A located in a loop Val448-Arg469 which has 21 aa and it does not has mutations, it is in a highly exposed on the surface of the NA, has aromatic amino acids conferring high immunogenicity with a molecular weight 2435 g/mol. Then, it was studied under computational docking with MCH II (HLA-DR), obtaining data that has a successful engagement with the peptide binding site of MCH II which was refined by molecular dynamics simulations, this coupler interactions between aa of peptide with P4, P6, P7, and P9 of MHC II, were by hydrogen bridges, hydrophobic interactions, links π-π, and Van der Waals forces. This theoretical data show a peptide which can be a potential epitopic used in vaccine. Authors thank to: Proyecto PIRIVE09-9 del ICyTDF, CB-62488 del CONACYT, Fundación Miguel Aleman AC, PIFI-SIP-COFAA-IPN y Sistema de BECAS del CONACYT. GAIT DYNAMICS ANALYSIS EVALUATES HINDLIMB REVASCULARIZATION Ríos 1 1 1 1 1 Amelia , Delgado Alexandra , Escalante Bruno , Santana Jesús . CINVESTAV MONTERREY, N.L. Peripheral arterial occlusive disease is a systemic disorder caused by the narrowing or occlusion of arteries resulting in a diminishment or detention of blood flow concluding in tissue damage of the ischemic area. In healthy individuals, revascularization response is the process that limits the extent of tissue damage. We have shown that gait locomotion analysis by video system represents an integrative model for the evaluation of mechanisms involved in the process of ischemia-induced revascularization. However, analysis by this system can be subjective and perception errors may be occurring. Thus, we present the optimization of a quantifiable, non invasive, reproducible method that analyzes ankle kinematics in rats using a two-dimensional digital video. Gait dynamics was filmed in hind limb ischemic rats with a high speed digital video camera. Images were collected and analyzed at 125 frames per second 3, 7 and 10 days after revascularization has started. An algorithm using IDL was devised to assess the following gait parameters: step length, walking speed, joint ankle angle, and gait cycle. Significant differences in walking speed and gait cycle were found between sham and ischemic animals for the three measured periods, whereas step length and joint ankle angle showed significant differences between sham and ischemic rats only at days 3 and 7. Gait dynamics was outlined in a highly sensible way by this computational analysis, showing that revascularization process starts as early as seven days post-ischemia. 150 EFFECT OF EXERCISE ON SERUM BDNF LEVELS IN SCHOOL CHILDREN. Ríos-Badillo V*., García-Arenas G, Goytia-Acevedo R., Maravilla A, Meza-Velazquez R., de Villa D. Departamento de Investigación, Facultad de Medicina, Gómez Palacio, Dgo, UJED. Mexico The present study was designed to test if the BDNF serum levels in children are modified by sport physical activity. A total of 67 children, aged 8-13 years, were recruited from sport teams (n=43) and elementary schools (n=24) in Torreon, Coahuila, Mexico. The physical activity group was established with the children that were doing exercise at least three or more days/week and at least one month before the test. In the control group were included sedentary children from elementary school. The relationship was tested by Chi square test for bivariate analysis and a logistic regression model for the multivariate analysis. The statistic significance was considerate with p <0.05. Further statistical analysis showed that having two or more siblings (OR = 2.61, CI95% 0.88-7.84, p= 0.05) was associated with decreased levels of BDNF, whereas in multivariate analysis these variables did not reach statistical significance (OR = 3.83, CI95%: 0.81-18.08, p= 0.089). Sport physical activity (OR= 0.34, CI95%:0.10-1.0, p=0.04) and the sport type (OR = 0.13, CI95%: 0.01-0.72, p=0.006) were significant and positively associated with increased levels of BDNF and this relationship remained associated in the multivariate analysis [(OR= 0.07, CI 95%: 0.008-0.62; p= 0.017), (OR=0.04, CI95%: 0.004-0.50, p= 0.010), respectively]. Age (OR= 1.26, CI 95%:0.43-3.65, p=0.62) and gender (OR = 1.43 CI95%: 0.49-4.21, p= 0.46) were not related with BDNF serum levels in children. This study supports the hypothesis that in children physical sport activity is associated with higher levels of BDNF and suggests that the type of sport could be involved. This work was supported by grant from FOMIX DGO88161. ALTERATIONS PRODUCED BY AN EXTRACT OF ROSMARINUS OFFICINALIS L. ON THE CONTRACTION INDUCED BY KCL AND ELECTRICAL STIMULATION. Rivero 1 1 2 Osorno Oscar , Montes de Oca Mejorada Misael , González-Trujano María Eva , Gómez 1 1 1 Acevedo Claudia , Ventura-Martínez Rosa. Departamento de Farmacología. Facultad de 2 Medicina. UNAM. Dirección de Investigaciones en Neurociencias del Instituto Nacional de PsiquiatrÍa ―Ramón de la Fuente Muñiz‖ Rosmarinus officinalis L. is a common spice that is widely used in folk medicine to treat intestinal spasms between many other disorders. The objective of this investigation was to evaluate the inhibitory effect of an ethanol extract of aerial parts of Rosmarinus officinalis on guinea pig isolated ileum. Six segments of 2.5-cm long of the whole ileum were obtained from each guinea pig. They were mounted in a 30 ml organ-bath containing KrebsBicarbonate solution maintained at 37°C and constantly bubbled with the mixture of O 2 and CO2. The resting tension was fixed at 1 g. The preparations were allowed to equilibrate for 60 min under continuous superfusion (10 ml/min). In one group of experiments, the effect of ethanol extract of Rosmarinus officinalis was evaluated in tissues precontracted by KCl [60 mM]; and, in other, in tissues precontracted by electrical stimulation (14 v, 0.3 Hz and 3ms) The tension changes of guinea pig ileum segments were recorded on a polygraph. The ethanol extract of Rosmarinus officinalis [600 µg/ml] induced an inhibition of the contractile effect of 62.97 ± 4.18% (n =6) and 59.32 ± 4.11 % ( n =6) in the tissue precontracted by high concentrations of potassium and electrical stimulation, respectively. These results suggest that ethanol extract of Rosmarinus officinalis exerts relaxant effects on intestinal smooth muscle, consistent with the popular use of the plant to treat gastrointestinal disorders. This study was supported by PAPIIT (grant IN201809-3). 151 RELATIONSHIP AMONG CHANGES IN HEMATOCRIT, ALBUMIN AND CORTICOSTEROID DOSE ON THE DISPOSITION OF TACROLIMUS DURING THE 1,2 FIRSTS SIX MONTHS AFTER RENAL TRANSPLANTATION. Robles-Piedras Ana Luisa , 1 3 4 Domínguez-Ramírez Adriana , Romano-Moreno Silvia , Fuentes-Noriega Inés , Mancilla5 5 1 Urrea Eduardo , González-López Eva Hilda . Universidad Autónoma Metropolitana2 3 Xochimilco, Universidad Autónoma del Estado de Hidalgo, Universidad Autónoma de San 4 5 Luis Potosí, Universidad Nacional Autónoma de México, Instituto Nacional de Cardiología ―Ignacio Chávez‖. Tacrolimus is a macrolide immunosuppressant that is safe and effective for the prevention of rejection after kidney transplantation. The oral bioavailability of tacrolimus averages 20% to 25%; however, the inter-individual variability in this parameter is large. Because of the poor correlation of dose to blood concentration between patients, the variability in pharmacokinetics and a relatively narrow therapeutic window, therapeutic drug monitoring of tacrolimus trough whole blood concentrations must be a standard practice. The objective of this evaluation was to determine the relationship among changes in hematocrit, albumin, and corticosteroid dosing on the disposition of tacrolimus during 6 months of treatment in renal transplant recipients. Study Design. Blood samples for the determination of trough tacrolimus concentrations were taken immediately prior to the morning dose, samples were collected according to the request of the attending physician. Clinical and dosage data were reviewed 6 months after transplantation. The analysis was conducted including 11 patients who were analyzed for hematocrit and albumin at the same time they are measured tacrolimus blood levels. Results. The mean age was 25.3 years (range 17 to 41 years) 4 of the patients were female. Levels of tacrolimus, hematocrit and albumin over the first 24 weeks post-transplant were documented and the estimated relative clearance of tacrolimus were calculated. Statistical evaluation of the data indicates poor correlation between relative clearance and both hematocrit and albumin levels and the mean oral steroid dose. Conclusions. This observation is of clinical significance because dose adjustment may be required to maintain blood concentrations within the therapeutic range in patients in whom hematocrit or albumin concentrations are changing. EFFECT OF EARLY DIABETES ON THE EXPRESSION OF ALPHA-1 ADRENOCEPTORS IN AORTA OF WISTAR KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS. 1 2 2 2 Rodríguez JE , Reséndiz-Albor AA , Arciniega-Martínez IM , Campos- Rodríguez R , Hong 3 1 1 E , Villafaña S . Laboratorio de señalización intracelular. Sección de posgrado. ESM-IPN. 2 3 Laboratorio de inmunidad de mucosas. Depto. Bioquímica. ESM-IPN. Sección externa de farmacología. CINVESTAV. Adrenergic receptors play an important role in the regulation of blood pressure. Diabetes and hypertension affect this mechanism, producing changes in vascular responses and exacerbating cardiovascular diseases. Several studies have mentioned that vascular changes are different in the early versus advanced stages of diabetes. For instance, in a recent study by our work group, a decrease in the vasopressor response to noradrenaline was found at 4 weeks of the evolution of diabetes in Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR). Among the changes that could take place in the early stages of diabetes to cause this decrease in vascular response is a decrease in the expression of alpha-1 adrenergic receptors. Therefore, the aim of the present study was to assess, by Western blot, the expression of the three subtypes of alpha-1 adrenergic receptors (alpha-1A,alpha-1B, alpha-1D) in the aorta of WKY and SHR rats with 4 weeks of the evolution of diabetes. The results show that whereas the condition of diabetes in WKY rats did not modify the expression of alpha-1B or alpha-1D receptors, the expression of alpha-1A was decreased compared with non-diabetic WKY group. On the other hand, this same condition in SHR rats led to a decrease in the expression of both alpha-1A and alpha-1D receptors, with no change observed in alpha-1B expression. In conclusion, the early stages of diabetes produce modifications in the expression of alfa-1 adrenergic receptors that could explain the decrease found in vascular responses. This work was supported by a CONACYT grant (#82599) and SIP grant (#20110176) COFAA- IPN. 152 PRESENTATION OF THE DEGREE IN PHARMACY (NEW CURRICULUM OF STUDIES 2008, SUPERIOR STUDIES CUAUTITLAN UNAM). DEGREE: BACHELOR IN PHARMACY Dra. Suemi Rodríguez Romo, Dra. Margarita Flores Zepeda, Dr. Arturo Aguirre Gómez, Q.F.B. Patricia Jeane Domínguez Quiñones Universidad Nacional Autónoma de México, Facultad de Estudios Superiores Cuautitlan The health, as a well and the individual's right and of the community, they require of specialized professionals in their knowledge, abilities, attitudes and aptitudes for a market every more competitive day. The objective of the Degree in Pharmacy is to form a health profesional as well as with knowledge, abilities and ethical attitudes. All this will allow him to: 1. Contribute in the development, modification, production and evaluation of drugs, medicines and cosmetics, 2.Select, provide and use medications rationally, 3. Be part of interdisciplinary teams in order to prevent, treat, and control deseases, and 4. Keep the health services quality Degree: Bachelor in Pharmacy. Plan of Studies, structure and organization: Duration: 8 semesters Total of subjects: 47 (obligatory 38, optional 18, terminal packages 9) Total of credits: 372 (obligatory 300, optional 72). Perspectives: Plan of Studies was approved in March 28, 2008. At the moment, they are studying the Degree in Pharmacy three generations of students. The graduate should assist social demands that the country requires in: Industry Chemist pharmacist:Pharma-chemist ,Pharmacist Industry, Auxiliary Health Products, Cosmetic industry, Alimentary industry, Hospital pharmacy and community, Clinical pharmacy, Education and investigation, Toxicology and legal chemistry, Biotechnology 1 STREPTOZOTOCIN SENSITIVITY IN THE ADULT WISTAR RAT. Rodríguez-Vázquez T , 1 1 1 1 Aguilar-Mariscal H , Pérez-Meza JA , Juárez-Rojo IE Blé-Castillo JL , Bautista-Escalante 1 2 3 1 CT , Patiño-Camacho SI , Aguilar-Mariscal I . Universidad Juárez Autónoma de Tabasco. 2 3 Villahermosa, Tab. México. Escuela Superior de Medicina IPN. México DF. Facultad de Biología. UAEM. Cuernavaca, Mor. México. ([email protected]) The diabetogenic doses of streptozotocin (STZ) in rodents are well known but diabetes differs from study to study, where this variation may be related to the induction scheme, severity of the diabetes and/or the strain of the animal model used. Therefore, we performed a study in which we determined the sensitivity of adult Wistar rat at two doses of STZ. A single high dose injection of STZ (HI STZ, 70 mg/kg, i.p.), and a single low dose injection of STZ (LO STZ, 50 mg/kg, i.p.) was administered at two groups of animals (n=10). Control animals were injected with saline solution. The animals were continuously observed during 30 days after STZ administration. Lethality, induction of diabetes, STZ resistant and body weight parameters were registered. Lethality, 70 and 10%; induction of diabetes, 20 and 70% (blood glucose levels > 250 mg/dL); STZ resistant, 10 and 20% were produced at HI and LO STZ respectively. At final experiments, rats with LO and HI STZ lost body weight (16 and 20% respectively) compared with initial body weight, while body weights of saline-treated controls gradually increased over time. Our results suggest that the LO STZ may be used as induction scheme of diabetes. This study was supported by PFICA (UJAT-2009-CO5-05). 153 S-ALLYLCYSTEINE PROTECTS AGAINST 1-METHYL-4-PHENYLPYRIDINIUM-INDUCED a a PARKINSONISM IN MICE. Patricia Rojas , Norma Serrano-García , Omar N. Medinac c b a Campos , José Pedraza-Chaverri , Perla D. Maldonado , Elizabeth Ruiz-Sánchez , Pedro a a b Montes del Carmen . Laboratory of Neurotoxicology and Laboratory of Cerebral Vascular Pathology, National Institute of Neurology and Neurosurgery, ―Manuel Velasco Suárez‖,; c Faculty of Chemistry, Department of Biology, National Autonomous University of Mexico (UNAM), University City, 04510, D.F., Mexico Parkinson´s disease (PD) is a neurological disorder characterized by degeneration and death of the dopaminergic neurons of the nigrostriatal pathway. Oxidative stress, via free radical production, plays an important role in its neurodegeneration. Antioxidants show effectiveness in reducing these deleterious effects. S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract, has multifunctional activity via different mechanisms and neuroprotective effects, exerted probably via its antioxidant or free radical scavenger action. 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse has been the most widely used model for assessing neuroprotective agents for PD. 1-methyl-4-phenylpyridinium (MPP+) is the stable metabolite of MPTP and causes nigrostriatal dopaminergic neurotoxicity. Oxidative stress, via free radical production, plays an important role in MPP +-induced neurotoxicity. We report the neuroprotective effect of SAC against oxidative stress induced by MPP+ in striatum of C57BL/6J mice. Mice were pretreated with SAC (125 mg/kg, ip) daily for 17 days followed by MPP + administration (0.72 mg/kg, intracerebroventricular), and were sacrificed 24 h later to evaluate different indexes of oxidative stress such as lipid peroxidation, and different antioxidant enzymes by a spectrophotometric method. Spontaneous locomotor activity using an open field system (behavioral phenotype), and dopamine content by HPLC (neurotransmitter mainly affected). MPP+ administration resulted in a significant decrease in dopamine levels in the striatum. Mice receiving SAC (125 mg/kg, ip) had significantly attenuated MPP+-induced loss of striatal dopamine levels (32%). The neuroprotective effect of SAC against MPP+ neurotoxicity was associated with blocked (100% of protection) of lipid peroxidation and reduction of superoxide radical production— indicated by an upregulation of Cu-Zn-superoxide dismutase activity—both of which are indices of oxidative stress. Behavioral analyses showed that SAC improved MPP +-induced impairment of locomotion (35%). We suggest that SAC attenuates locomotor impairment produced by MPP + neurotoxicity, and that an antioxidant effect against oxidative stress may be partly responsible for its neuroprotective effects. GASTROPROTECTIVE EFFECT OF CARBENOXOLONE AND 3- HIDROXIMASTICADIENONIC ACID IN THE MODEL OF GASTRIC DAMAGE INDUCED 1 2 BY KETOROLAC IN THE RAT. Rojas Zaldívar E , Castañeda Hernández G , Navarrete 3 1 1 Castro A , Chávez Piña AE . SEPI, Programa Institucional en Biomedicina Molecular, 2 3 ENMH-IPN. Departamento de Farmacología, CINESTAV-IPN, México, D.F. Departamento de Farmacia, Facultad de Química UNAM. Ketorolac is an NSAID (non-steroidal anti-inflammatory drug) with analgesic effect widely used in the treatment of postoperative pain, which in its adverse effects ketorolac causes severe gastric lesions. In this study the effect of the gastroprotective compounds carbenoxolone (synthetic) and 3- -hidroximasticadienonic acid (triterpene isolated from the bark of Amphiterygium adstringens) was evaluated against gastric damage induced by ketorolac in rat. Wistar female rats were used (170-180 g). Control groups of ketorolac (50 mg/kg p.o.), carbenoxolone (100 mg/kg p.o.) and 3-hidroximasticadienonic acid (100 mg/kg p.o.) were formed; groups of carbenoxolone (100 mg/kg p.o.) or triterpene (100 mg/kg p.o.) with ketorolac (50 mg/kg p.o.) were evaluated for their gastroprotective effect. After 3 hours the number of hemorrhagic gastric lesions was determined. Results showed a statically significant reduction in the number of gastric lesions presents with the combination of carbenoxolone or 3-a-hidroximasticadienonic acid with ketorolac compared with the use of ketorolac alone. In conclusion, our results suggest the gastroprotective effect of both compounds in ketorolac-induced gastric damage in the rat. The combination of those compounds with NSAIDs should be considered as alternative to reduce gastric adverse effects. 154 MORPHO-HISTOLOGICAL CHANGES IN GONADS OF RATS FEMALES TREATED PERINATALLY WITH TESTOSTERONE PROPIONATE AND COUMESTROL. Ruíz de Chávez Mejía Julio Agustín, Rosales Torres Ana María, Herrera Gutiérrez Héctor, Rivero Juan José, Ávalos Rodríguez Alejandro, Zamora Gutiérrez D, Vergara Onofre Marcela. Departamento de Producción Agrícola y Animal. Laboratorio de Bioquímica de la Reproducción, Universidad Autónoma Metropolitana Unidad Xochimilco (UAM-X). We studied modifications produced in rats females adults by the administration with treatments applied neonatally to the rats, since they can interact during the sexual differentiation and trying to revert these modifications with a phytoestrogen (Coumestrol). We analyzed modifications to the body weight of hypothalamus, and reproductive tract as well as measured and structures of this last one, besides observing changes in the sexual behavior of the rats. Females were used offspring of Wistar rats, that were divided in 4 groups of 5 rats to which at the time of been born hormonal treatments were administered to them that were: Group one or Control (GC) safflower oil also used like vehicle (20µl), group two Coumestrol (Cou) 100 µg in 20µl of vehicle, group three Testosterone Propionate (TP) 30 µg in 20 µl of vehicle and group four Coumestrol-Testosterone Propionate (TP+Cou) 30 µg and 100 µg respectively in 40 µl of vehicle. The rats were weight every week until the 120 days of age, subsequent to this were sacrificed and the weight of the reproductive tract and the hypothalamus was obtained. The sexual conduct was evaluated with stallion and its express receptivity by the Quotient of Lordosis (QL). The variations of weight in reproductive tracts were visible thus also like in their longitudinal measures. In order to compare the results obtained between the groups, and differences between these an Analysis of Variance (ANOVA) was realized. Subsequent to this we realized the test of Tukey. The sexual behavior was modified like the presence of vaginal opening, being the treatment of testosterone propionate Testosterone the one that obtained more morphologic changes and without managing to revert these modifications with the treatment of Coumestrol (p<0.05). PHARMACOLOGICAL PROFILE OF THE DOPAMINE D2-LIKE RECEPTOR SUBTYPES MEDIATING INHIBITION OF THE SYMPATHETIC VASOPRESSOR OUTFLOW IN PITHED RATS Inna I. Ruiz-Salinas, Abimael González-Hernández, Guadalupe Manrique-Maldonado, Bruno A. Marichal-Cancino, Alain H. Altamirano, Carlos M. Villalón Farmacobiología, Cinvestav-IPN (Sede Sur), 14330 Mexico D.F., Mexico Dopamine plays an important role in cardiovascular regulation by interacting with D 1-like and D2-like receptors (and, sometimes, with adrenoceptors). Indeed, our group has recently shown that activation of prejunctional D2-like receptors inhibits the sympathetic vasopressor outflow in pithed rats. This study set out to establish the role of the corresponding subtypes (i.e. D2, D3 and D4) in the above sympatho-inhibition. Pithed rats were treated i.v. with gallamine (25 mg/kg) and desipramine (50 μg/kg), followed by i.v. continuous infusions of saline (0.02 ml/min) or quinpirole (D2-like receptor agonist; 1 μg/kg.min) in animals receiving i.v. vehicle or the subtype-selective antagonists L-741,626 (D2), nafadotride (D3) or L-745,870 (D4). Then, stimulus-response curves (electrical stimulation of the spinal T 7-T9 segments; 0.03-3 Hz; 50 V and 2 msec) resulted in frequency-dependent vasopressor responses. Quinpirole inhibited the sympathetic vasopressor outflow (without affecting the vasopressor responses to i.v. noradrenaline). This quinpirole-induced sympatho-inhibition was: (i) unaltered by 100 μg/kg L-741,626; (ii) partially blocked by 100 μg/kg L-745,870 and 30 μg/kg nafadotride; and (ii) abolished by 100 μg/kg nafadotride. These doses of antagonists (which are high enough to completely block their respective receptors), did not modify per se the sympathetically-induced vasopressor responses. The above results suggest that the D 2-like receptors mediating quinpirole-induced inhibition of the sympathetic vasopressor outflow closely resemble the activation of the D3 and, to a lesser extent D4 receptors subtypes. 155 ANTIFUNGAL DRUGS DO NOT ALTER THE INFECTIVITY OF S. SCHENCKII. Sabanero López M., Loza Manjarrez G., Flores Villavicencio LL., Palomino Torres N., Sandoval Bernal G. Departamento de Biología, División de Ciencias Naturales y Exactas Campus Guanajuato. Universidad de Guanajuato, Noria Alta S/N, Col. Noria Alta, Guanajuato, Gto. CP 36050 e-mail: [email protected] S. schenckii is a dimorphic fungal pathogen, and is the causing agent of sporotrichosis. In this work the epithelial cell response to invasive infection by S. schenckii; which was exposed to antifungal drugs was analyzed. Strain MP-102 S. schenckii was growth in YPG medium by 72h at 37°C. After, antifungal drugs treatments (azoles=500μg/mL and polyene=100µg/mL), it is realized S. schenckii – epithelium cell interaction. The results shown that normally, there is an intimate adherence of the pathogen to epithelial cells. The growth kinetics showed that azoles (Itraconazole and Fluconazole), affect growth (40% and 27%), while Ketoconazole proved to be ineffective. Amphotericin B, a drug from the polyene family, drastically affected growth (98%). Structurally, anti-cytoskeleton antibodies indicated alteration in the structures of the cells that interacted with the fungi exposed to antifungal agents. The epithelial cell damage is similar to that caused S. schenckii without drug treatment. Moreover, three S. schenckii antigenic proteins (Mr ≥ 90, 70 and 40kD) were expressed, with the pharmacological stress and in its absence. The results of this study, indicate protein synthesis is not affected even after pharmacological stress, pathogenicity factors that affect the epithelium integrity prevail. This will have an impact, on the evaluation of an effective therapy for sporotrichosis. VALIDATION OF CERTAIN REAGENTS OF EVALUATION IN BIOCHEMISTRY AND MOLECULAR BIOLOGY AT THE FACULTY OF MEDICINE, UNAM Saldaña Balmori Yolanda*, Delgadillo Gutiérrez Héctor Javier**. *Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, **Departamento de Sistemas Biológicos. Universidad Autónoma Metropolitana, Xochimilco. On Faculty of Medicine, UNAM during more than 50 years departmental examinations had been made and there were not had found references to validate them. Interesting having quality assessments, this work explores to know validity of assessment used to test a test of Biochemistry and Molecular Biology in school year 2009-2010, in his case, we selected the accepted questions and we had suggested to discard the unfit. In this study we had used four techniques: 1) Index of difficulty (Pi), which is the relationship between the rate of questions with right answers between the number of total questions, 2) Discrimination index (Di), which discriminates between 27% of items that they have the highest score against 27% of those who have the lowest, 3) Coefficient of discrimination (Rpbis), where it involves 100% and 4) Alpha of Cronbach which gives the reliability of the reagents and indicates what would happen to database if it eliminates some questions to be able to change untrusted items. The significance of this work is to identify the questions that complies with at least three of the four techniques of validation to form a bank of items; questions that are not in these circumstances it was suggested to be eliminated or modified to revalue to enrich the bank reagents. The results indicate that 276 questions that constitute 100% of those applied in the 4 departmental examinations, 22 (8%), not covered with any of the 4 techniques; 45 questions (16%), only one; 35 (13%), with two; 80 (29%), with three and 94 (34%), with the 4 techniques here worked. It was concluded that from 276 questions employed in the four exams at period 2009-2010, 174 (69%) are well developed and 102 (31%), should be revised or deleted to improve the standards of quality. 156 PARADOXICAL RESPONSE IN THE ELEVATED PLUS MAZE MODEL IN RATS: EFFECT OF DIAZEPAM ADMINISTRATION. Saldívar-González, JA., Fiesco-Roa MO., CamposRodríguez UE. Faculty of Medicine. Dep. Pharmacology. Lab. of Neuropsicopharmacology. University of Mexico. [email protected] In the last years our research group has been studying anxiety vulnerable individuals in rats. In a previous study, we have reported increased anxiety response elicited by diazepam (Dz) administration in a subgroup of rats. A paradoxical effect of benzodiazepines, i.e., anxiogenic, rather anxiolytic one has also been reported. Thus, the present work was performed with the aim to demonstrate a putative anxiogenic action of diazepam administration in rats in the elevated plus maze (EPM) anxiety animal model. In the present research male Wistrar rats were used. The groups tested in the EPM model were: Control non-manipulated, saline control and diazepam 1, 3 and 5 mg /kg. The test lasted 5 min and was performed in a red dim light room. The time that animals spend on the open arms and the number of crossings from closed to open arms was recorded. A group of control nonmanipulated animals were retested in the EPM after Dz 1 mg/kg IP injection. Collected data was analyzed by Kruskal Wallis ANOVA followed by the Mann Whitney U test. A group of animals showing extremely low (paradoxical) open arms time values despite Dz injection were observed. The percent of paradoxical subjects per group was 15.7, 8.3 and 20 for 1, 3, and 5 mg/kg respectively. Control non manipulated and saline groups showed 17.6 and 31 % of paradoxical subjects. It is interesting to note that Dz 1 mg/kg did not exert any effect in paradoxical control non-manipulated animals. The results are discussed in terms of anxiety vulnerable animal subgroup. The possibility of atypical GABA A mode of functioning is also discussed. UP REGULATION OF MRNA OF 5-HT3 RECEPTOR IN TASTE BUDS FROM RATS WITH EXPERIMENTAL DIABETES MELLITUS. Martha Angélica Salgado Chávez, and Rosalio Mercado Camargo. PIMCB-Facultad de Químico Farmacobiología. U.M.S.N.H. Morelia, Mich. México. Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia. In patients with diabetes mellitus there are reports of changes in taste perception. Taste is a vital sense for preventing consumption of poisonous foods as well as searching for nutrients. Taste sensation is transduced in secondary sensory cells located at the taste buds which are specialized structures in the oral cavity. Reported results show that the taste buds in the adult rat express two types of serotonin receptors: receptor type 5-HT1A and 5-HT3. 5-HT1A receptors are located in taste cells that do not express serotonin, in type II cells, while 5-HT3 receptors are expressed in gustatory afferent fibers. Alterations of taste are characteristics of diabetic patients, however, is not known whether the Diabetes Mellitus there are changes in the expression of the mRNA of the 5-HT3 receptor involved in taste perception and transmission. The aim of the present study was to determine if the expression mRNA of 5HT3 receptor changes in the circumvallate papilla of rats with experimental diabetes mellitus (EDM). We determined the expression of mRNA of the 5-HT3 receptor by RT-PCR in the circumvallate papilla of rats with one week and eight weeks of EDM. The results showed that at one week of EDM there are no changes in the expressions and at 8 weeks there are increases of the expression of the mRNA of 5-HT3 receptor. These data suggest us that the up regulation in the expression of 5-HT3 receptor in chronically diabetes mellitus is a compensatory mechanism in order to transduce gustatory signals. The present work was partially supported by: CIC-U.M.S.N.H. (2011), CONACyT: 226645 157 GLYCATION AND GLYCOSYLATION OF SERUM CHOLINESTERASE IN DIABETIC MICE 1 2 TREATED WITH GLYCINE. M en Biol. Exp. Noe Salinas Arreortua, Dr. Francisco Javier 2 1 Alarcón Aguilar, Dr. José Luis Gómez Olivares. Universidad Autónoma Metropolitana – 2 Iztapalapa. Profesor Titular C. Departamento de Ciencias de la Salud. Posgrado en Biología Experimental. UAM-I. Due to high glucose levels in Diabetes Mellitus (DM) proteins experience glycation. Structural changes of glycated proteins induce physiological complications in T2DM by the formation of advanced glycation end products. Studies on mice, rabbits and diabetic patients showed that glycine significantly decreases the hemoglobin glycation, suggesting that this amino acid may prevent protein glycation. To evaluate the glicine therapeutic effects we used CD-1 mice as an experimental model of DM. Three mice groups were formed: 1) a healthy group as negative control, 2) a diabetic groups as positive control, and 3) a diabetic group treated with glycine (0.1 g / kg). Cholinesterase activity was measured by the Ellman method, and the total protein by the Bradford method. Glycated proteins were recovered from an affinity matrix such as boronic acid or lectins. The specific activity of acetylcholinesterase (AChE) increased 30% in diabetic mice with respect to the healthy control. For butyrylcholinesterase (BuChE), on the other hand, the specific activity increased two fold against the healthy control. Similar observations have been described for human diabetic patients (Salceda et al., 2000). Upon glycine treatment, no significant differences were detected in the amount of glycated AChE, whereas BuChE displayed an opposite behavior. Further, lectins assay suggest that the post-trascriptional processing in both AChE and BuChE is impaired in the DM group, while the role of glycine is associated to the decrease of specific glicosilation and glycation. Glycine treatment apparently reflects a decrease in the incorporation of oligosaccharides and abnormal protein glycation. MOLECULAR DOCKING AND INHIBITION STUDIES IN ENTAMOEBA HISTOLYTICA 1,2 3 HEXOKINASE. Saucedo-Mendiola María Leticia , Salas-Pacheco José Manuel , Avitia1,4 1 1 Domínguez Claudia , Araujo-Conteras Jesús , Ávila-Rodríguez Armando , Ávila-Rodríguez 1 1 1 Humberto , Téllez-Valencia Alfredo . Centro de Investigación en Alimentos y Nutrición, 2 3 FAMEN, UJED. Facultad de Ciencias Químicas, UJED. Instituto de Investigación Científica, 4 UJED. CIIDIR-IPN, Unidad Durango. Correspondence: [email protected]. Amebiasis caused by parasite Entamoeba histolytica, affects more than 10% of the world’s population, and untreated infection may lead to severe complications including hepatic amebiasis and intestinal tissue destruction. More than 50 million people worldwide are infected, and up to110,000 of them die every year. Only malaria and schistosomiasis surpass amebiasis as parasitic causes of death. Metronidazole and other 5-nitroimidazoles are the most commonly used drugs for the treatment of amebiasis. Besides their relative ineffectiveness against luminal cyts, these drugs have serious side effects. Therefore, there is a necessity for new drugs to treat the disease. In this context, as E. histolytica depends on glycolysis to obtain ATP for cellular work. According to metabolic flux studies, hexokinase exerts the highest flux control in this metabolic pathway. For this reason we used to search inhibitors through molecular docking and kinetics assays. First a tridimensional model of Entamoeba histolytica hexokinase (EhHK) was constructed by homology modeling. Docking at the ATP binding site in the enzyme was made using MOE software and the Hit Finder library of small molecules from Maybridge. The one hundred molecules with the best score in docking were purchased and assessed to determine their inhibition capability. Results showed that three molecules inhibited EhHK with an IC 50 of 48 μM for disodium 5-nitro-2-[2-(4-nitro-2-sulfonatophenyl)vinyl]benzenesulfonate (C1), 91 μM for 3,5di(3,4,5-trimethoxybenzylidene)tetrahydro-2H-pyran-4-one (C2) and 96 μM for 5,6,7-trimethoxy-2(2,3,4-trimethoxybenzylidene)indan-1-one (C3). Docking analyses indicated that compound C1 made a hydrogen bond with Arg66, C2 with Thr63, Arg66, Arg320 and Thr396, while C3 did it with Thr63, Arg320 and Thr396. Furthermore, aminoacids Gly203, Gly395 and Thr396 were common for the interaction of these small molecules with the enzyme. In conclusion, we found three new inhibitors of EhHK that can serve as leads in the search of a new chemotherapy against amebiasis. 158 STUDY OF THE INTERACTION BETWEEN THE ADRENERGIC SYSTEM AND RENINANGIOTENSIN SYSTEM AT VASCULAR LEVEL. Sebastián G., Estévez M., Franco A., Hong E., Villafaña S. National Polytechnic Institute, Mexico. Email:[email protected] The main difficulty to identify the causal mechanisms of arterial hypertension and achieve an optimal control is the wide variety of systems involved in blood pressure regulation and the complex interaction between them. Some of the most important are the adrenergic and reninangiotensin systems through its receptors such as α1 (α1A, 1B and 1D) and the AT1 and AT2 receptors respectively. Due to the importance of these systems the aim of this study was to evaluate in vitro the interaction between AT1 and α1 adrenergic receptors. We used endothelium-denuded aortic rings from male Wistar rats, the aortic rings were placed in 10 ml chambers with Krebs-Henseleit solution at 37 °C and pH 7.4 with constant oxygenation (95% O2, 5%CO2), the contractile force was recorded with a Grass Instruments equipment. Concentration-response curves to phenylephrine, angiotensin II and phenylephrine with different concentrations of angiotensin II were constructed. The results obtained showed that the combination of phenylephrine and angiotensin II at lower concentrations produce higher responses to phenylephrine than phenylephrine alone, however when we increase the concentrations of both agonist appears a decrease in the magnitude of the responses. These results suggest that when two agonists with common signaling pathways are combined at lower concentration the response obtained is like a synergistic effect, but as their concentrations are increased there is a competition at transductional level that decrease the contractile responses. This work was supported by IPN-SIP-20100592 ANTIDEPRESSANT-LIKE EFFECT OF A GINKGO BILOBA EXTRACT (EGB 761) IN THE MOUSE FORCED SWIMMING TEST: ROLE OF OXIDATIVE STRESS. Norma Serranoa a b b García , Patricia Rojas , Omar N. Medina-Campos , José Pedraza-Chaverri , Sven O. c d a aa Ögren , Carolina Rojas . Elizabeth Ruiz-Sánchez , Pedro Montes del Carmen Laboratory b of Neurotoxicology, National Institute of Neurology and Neurosurgery; Faculty of Chemistry, c Department of Biology, National Autonomous University of Mexico; Department of d Neuroscience, Karolinska Institute, Sweden; Institute of Biomedical Research, Department of Physiology, National Autonomous University of Mexico D.F., Mexico Depression is one of the most prevalent, serious, recurrent, incapacitating and costly psychopathologies worldwide with an incidence of 15-25%. Oxidative stress, via free radical production, plays a role in depression and animal models for depression-like behavior. Preclinical studies have suggested that antioxidants may have antidepressants properties. EGb761 is a welldefined mixture of active compounds extracted from Ginkgo biloba leaves. This extract is used clinically due to its neuroprotective effects, exerted probably via its potent antioxidant or free radical scavenger action. The aim of this study was to investigate the antidepressant-like effect of EGb761 due to its antioxidant role against oxidative stress induced in the forced swimming test, the most widely used preclinical model for assessing antidepressant-like behavior. Male BALB/c mice were pretreated with EGb761 (10 mg/kg, ip) daily for 17 days followed by the forced swimming test and spontaneous locomotor activity. Animals were sacrificed to evaluate indexes of oxidative stress (lipid peroxidation, different antioxidant enzyme activities) by spectrophotometric method. Neurotransmitters related to depression/depression-like behavior such as serotonin and dopamine in different brain regions (midbrain, hippocampus and prefrontal cortex) using an HPLC method. EGb761 significantly decreased the immobility time (39%) in the forced swimming test. This antidepressant-like effect of EGb761 was associated with a reduction in lipid peroxidation and superoxide radical production (indicated by a downregulation of Mn-superoxide dismutase activity), both of which are indicators of oxidative stress. The protective effect of EGb761 is not related to excitatory or inhibitory effects in locomotor activity, and was also associated with the modulation of serotonergic and dopaminergic neurotransmission in mesocortical and mesolimbic pathways. It is suggested that EGb761 produces an antidepressant-like effect, and that an antioxidant effect against oxidative stress may be partly responsible for its observed neuroprotective effects. 159 METFORMIN INCREASES PARAOXONASE (PON) ACTIVITY IN OBESE SUBJECTS 1 2 2,3 3 Martha Patricia Sierra-Vargas , Alejandra Meaney , Eduardo Meaney , Guillermo Ceballos . 1 2 Instituto Nacional de Enfermedades Respiratorias ―Ismael Cosío Villegas‖. Unidad 3 Cardiovascular, Hospital Regional 1° de Octubre, ISSSTE. Escuela Superior de Medicina, Instituto Politécnico Nacional. Mexico City, Mexico. Metformin (Mt) is an insulin-sensitizing biguanide used to treat type 2 diabetes (DM2). Despite its benefits in overweight patients with or without DM2, its antioxidant activity has not been widely studied. Paraoxonase is an antioxidant enzyme related to High Density Lipoproteins (HDL) that prevents lipid peroxidation. We wonder if the beneficial effects of Mt can be linked to modulation of PON activity. The aim of this study was to explore the effects on PON activity in non diabetic obese adults treated with Mt. We enrolled sixty patients with metabolic syndrome (MS) from the Risk Factors Outpatient Clinic of the Cardiovascular Unit, Regional Hospital ―1° de Octubre, ISSSTE‖. Patients were randomly assigned into two groups. Both groups received similar dietary counseling, but one group received 850 mg metformin daily during one year. Blood samples were obtained at the beginning and the end of the study and PON activity was determined. HDL concentration and paraoxonase activity were similar in both groups at the start of the study. After 1 year, there were no differences on HDL concentration between groups. However, treated group revealed significantly higher paraoxonase activity than the control group (3.2 ± 2.3 vs 5.7 ± 3.3 nmol p-nitrophenol/mg prot). Our results show that even in the absence of a net increase in HDL concentration, the MT-induced an increase in PON activity. This increase may have preventive effects on cardiovascular risk related to oxidative stress. Further studies are required in order to elucidate the mechanism(s) by which Mt increases PON activity. ANTIOXIDANT ACTIVITY OF ROSMARINUS OFFICINALIS IN THE PREVENTION OF EXPERIMENTAL ALCOHOLIC LIVER CIRRHOSIS. Sonia Sifuentes-Franco*, Rosalinda Gutiérrez-Hernández and Patricia Yahuaca-Mendoza. Programa de Doctorado en Farmacología, U.A. de Medicina Humana, Universidad Autónoma de Zacatecas. Zacatecas, México. E-mail: [email protected] Alcoholic liver cirrhosis is a condition that, at present, is among the leading causes of death worldwide. The liver damage characteristic in cirrhosis is caused, among others, by increasing free radicals which trigger oxidative stress, and promoting disease progression. Currently there are few treatment options, so it is important to study alternative prophylactic therapy in alcoholic cirrhosis, such as herbal medicine, with high antioxidant effect, as the case of Rosmarinus officinalis. In this work we studied the prophylactic effect of Rosmarinus officinalis in experimental alcoholic cirrhosis. Male Wistar rats (100-150 g) were divided into 4 experimental groups, which were orally administered for 12 weeks: 1) vehicle control group (saline); 2) cirrhosis group (3 g/kg, 35% ethanol in saline); 3) Group R. officinalis (10 mg/kg); 4) Prevention Group: co-administration of ethanol + R. officinalis (similar schemes to groups 2 and 3). At the end of treatments was determined oxidative stress, enzymatic and metabolic indicators of liver damage, histology and tumor markers. R. officinalis prevents the increase of lipid peroxidation induced by ethanol, and the loss of red cell membrane stability, recovering to normal. Similarly, depletion in glycogen storage was avoided by R. officinalis, which is consistent with partial reduction of bilirubin levels and activity of -GTP, ALT and AST. Measurement of carcinoembryonic antigen (CEA) and alphafetoprotein (AFP) in cirrhosis, indicated an increase over the control (493% and 110% respectively), which was prevented in a greater extent for CEA (27%) and partly for AFP (73%), to administer R. officinalis. The biochemical findings were confirmed by histological studies, where the distortion of the hepatic parenchyma and collagen deposition was prevented by treatment with R. officinalis. These results suggest a prophylactic effect of Rosmarinus officinalis, that could be used in the management of chronic liver damage. Project funded by SEP-PIFOP 2002-33-04 and Fondo Sectorial SEP-CONACYT, Ciencia Básica, CB-2008-0-105986 * Number 15609 CONACYT Project Fellow. 160 ACUTE TOXICITY AND EFFECTS ON MOUSE LOCOMOTOR ACTIVITY OF A NEW DOPAMINE BORON CONTAINING COMPOUND DESIGNED BY USING IN SILICO 1 1 2 1 TOOLS Soriano-Ursúa MA , Correa-Basurto J , Padilla-Martínez I , Domínguez-Campos A , 2 3 1 1 Ocampo-Mendoza K , Ocampo-López JO , Trujillo-Ferrara JG . Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México. 2 Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, 3 Avenida Acueducto s/n, Barrio La Laguna Ticomán, 07340, México Laboratorio Médico Químico Biológico S.A. de C.V., Cerro San Antonio 151, 04400, México ([email protected]). The development of D2 dopamine receptor (D2DR) ligands is an attractive task, as D2DRagonists are used for Parkinson disease treatment, and D2DR-antagonists are potentially applicable in schizophrenia or drug-dependence. The aim of the current contribution was to identify high affinity D2DR-ligands by building a D2DR tridimensional homology model and carrying out both model validation and screening studies for well-known and new proposed ligands. We found boron containing compounds with the predicted high affinity for D2DR, then characterized one such compound. This compound was tested in mice and according to the LD50 showed an acute toxicity similar to an equimolar quantity of levodopa. In addition, the intraperitoneal administration of this compound, in aqueous solution or in liposomal formulation, disrupted the locomotor activity evaluated in an open field model, rotarod, gait and pole tests. These results suggest that this new compound acts on the dopaminergic system of mice. Supported by grants from SIP-IPN, CONACyT and INNOVAPyME/CONACyT program. CELL-BASED AND IN-SILICO STUDIES ON THE HIGH INTRINSIC ACTIVITY OF TWO BORON-CONTAINING SALBUTAMOL DERIVATIVES AT THE HUMAN Β21 2 2 ADRENOCEPTOR. Soriano-Ursúa MA , McNaught-Flores D , Nieto-Alamilla G , Correa1 1 2 1 Basurto J , Trujillo-Ferrara JG , Arias-Montaño JA . Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, México, D.F., México; 2 Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del I.P.N., Av. IPN 2508, 07360 México, D.F., México. ([email protected]) Salbutamol is a well-known partial agonist at the β2 adrenoceptor (β2AR). In previous works we have reported the development of two boron-containing salbutamol derivatives (BCSD) possessing greater potency and efficacy than its precursor for inducing β 2AR-mediated smooth muscle relaxation in guinea-pig tracheal rings. However, the mechanism involved in this pharmacological effect is unknown. In order to obtain insight into this issue, we carried out binding and functional assays in HEK-293T cells transfected with the human β2AR (hβ2AR). The transfected hβ2AR showed similar affinity for BCSD and salbutamol, but BCSD were more potent and efficacious to induce the accumulation of endogenous cAMP. In addition, molecular modeling showed high affinity of BCSD on the hβ 2AR and differences in their interaction with the fifth and sixth transmembrane receptor domains in its active and inactive conformational states. Together, these data show that BCSD induce and stabilize conformational states of the hβ2AR with high capability to stimulate AMPc production and thus smooth muscle relaxation. Funded by grants from SIP-IPN and CONACyT. 161 LOCOMOTOR EFFECTS OF NANOPARTICLES CONTAINING LEVODOPA ON A MPTP1 1 INDUCED PARKINSON’S DISEASE MODEL. Soriano-Ursúa MA , Aguilar-Faisal L , 2 2 1, 1 Jiménez-Estrada I , Ocampo-López JO , Trujillo-Ferrara JG *. Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, 11340, México. 2 Departamento de Fisiología, Bioquímica y Neurociencias, Centro de Investigación y Estudios Avanzados del I.P.N., Av. Instituto Politécnico Nacional 2508, 07360 México. 3 Laboratorio Médico Químico Biológico S.A. de C.V., Cerro San Antonio 151, 04400, México. ([email protected]) Levodopa administration is considered a cornerstone in the palliative Parkinson’s Disease (PD) treatment. The strategies for improving the ability of this drug to reach to Central Nervous System (CNS) have been studied widely, obtaining some advances in this field. In this work, we developed several liposomal formulations containing equivalent levodopa amounts included in nanoparticles (all smaller than 450 nm, measured by atomic force microscopy). A notable improvement was found regarding dopamine availability in the CNS compared to levodopa administration in aqueous solution. Then, we measured the effects of its intraperitoneal administration on total motor activity, rotarod, gait and pole tests on a acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced murine PD model. The observed effects in these tests depended on the nanoparticle composition, which could be related to the dopamine level in the CNS of the treated mice. Funded by grants from SIP-IPN, CONACyT and INNOVAPyME program. ANTI-INFLAMMATORY EFFECT OF SENNA VILLOSA CHLOROFORM EXTRACT AND (8-HYDROXIMETHYLEN)-TRIEICOSANYL ACETATE, IN A SKIN INFLAMMATION 1 2 MODEL. Susunaga Notario Ana del Carmen , Almanza Pérez Julio César , Zavala Sánchez 3 3 2 Miguel Angel , Pérez Gutiérrez Salud , Román Ramos Rubén , Alarcón Aguilar Francisco 2 1 2 Javier . Posgrado en Biología experimental, D.C.B.S., UAM-I, . Lab. Farmacología, Depto. 3 Ciencias de la Salud, UAM-I, . Lab. Productos Naturales, Depto. Sistemas Biológicos, UAMX. Mexican traditional medicine used a great variety of plants to treat different diseases, one of which is Senna villosa Mill. (Leguminosae) commonly named Salché, which grows in Peninsula of Yucatan, Mexico. The ancient Mayas used the leaves to ease unidentified skin infections, dysmenorrhea and inflammatory diseases. The leaves were extracted with CHCl 3 under reflux for 4 hours, the solvent was removed under reduced pressure and the residue was chromatographed on silica gel and eluted with hexane, while increasing the polarity with ethyl acetate. The antiinflamatory effect, were studied on 12- O-tetradecanoil phorbol-13acetate (TPA) induced ear edema on mice. Edema was induced on the right ear by topical application of 2.5 μg/ear TPA (in 20 μg/acetone). The left ear (control) received the vehicle (acetone). Chloroform extract and the (8-hydroximethylen)-trieicosanyl acetate and indomethacin 2.0 mg/ear dissolved in acetone were applied 30 minutes after TPA administration to the right ear. The left ear was treated with the vehicle (acetone) only. The extent of inflammation in the control group was determined as the difference in the weight of the TPA-inflamed ear and the vehicle-treated ear. In all groups, the edema was allowed to develop for 6 hours. Then, the animals were sacrificed by cervical dislocation, and plugs (diameter of 6 mm) of the central portion were taken from both ears and weighed. The chloroform extract of Senna villosa and its component (8-hydroximethylen)-trieicosanyl acetate showed an anti-inflammatory effect, making 39.77±4.74 and 36.24±7.9 percent of inhibition, respectively, while indomethacin caused the 33.91±6.39 percent of inhibition. Because the induced inflammatory effect by TPA is the result of the acute inflammation that stimulate the production of araquidonic acid, several prostaglandins and leucotrienes (2,3,4), the anti-inflammatory effect of Senna villosa may be explained by inhibition of the phospholipase A2 and, consequently, synthesis of prostaglandins. 162 1 2 HEMATOPOIETIC ACTIVITY OF Urtica dioica IN VITRO. Rafaela Tapia Aguilar, Alma 2 3 1 Delia Ramírez Cruz, Ana María González Gutiérrez, Abigail Aguilar Contreras, Rodolfo 1 2 Velasco Lezama. Departamento de Ciencias de la Salud. Licenciatura en Biología 1,2 3 Experimental. Universidad Autónoma Metropolitana-Iztapalapa. México, D. F. Herbario del Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI. [email protected]. Deficiency of iron is the nutritional deficiency most prevalent and the main cause of anemia around the world. Due to Its high concentration of iron Urtica dioica is used popularly to counteract anemia. The goal of this study is to determine the ability of two varieties of Urtica dioica to stimulate the proliferation of hematopoietic cells in vitro.The plants were acquired in the "Sonora Market" of Mexico City, dried aerial parts of each plant were ground and macerated separately in hexane, dichloromethane, methanol and water at room temperature for 24 hours, solvents were removed until total dryness. Also a decoction of the aerial parts was prepared. Dilutions of 1, 10 and 100 µg/mL were prepared for in vitro assays. CD1 female mice 8-12 weeks were sacrificed by cervical dislocation, bone marrow and spleen cells were obtained and cultured with RPMI-1640 medium supplemented with 10% of inactivated calf serum. Cultures were incubated at 37°C for 72 hours with 5% CO2 and 95% air. Control cultures without extracts were prepared simultaneously. Each extract was assayed four times by triplicate.Concentration of 100 µg/mL from hexane extract and decoction of U. dioica L. stimulated the proliferation of spleen cells, increasing 1.8 times the cell population compared to control cultures. Other materials presented cytostatic effect, except concentrations of 100 and 10 µg/mL of methanol extract which inhibited 50 and 80% the cell proliferation, respectively. While, only concentration 10 µg/mL of the aqueous extracts from U. dioica var. angustifolia had stimulating activity. Concerning bone marrow cultures, concentration of 100 µg/mL of methanol and watery extracts from U. dioica L stimulated the cell proliferation significantly, other doses increased poorly the cell concentration. Meanwhile U. dioica var. angustifolia presented cytostatic effect. U. dioica L had better hematopoietic activity than U. dioica var. angustifolia. COMPARATIVE STUDY OF ANTIBACTERIAL ACTIVITY IN VITRO OF TWO VARIETIES 1 2 2 OF Urtica dioica. Rafaela Tapia Aguilar, Ana María González Gutiérrez, Alma Delia 3 1 1 Ramírez Cruz, Abigail Aguilar Contreras, Rodolfo Velasco Lezama. Departamento de 2 1,2 Ciencias de la Salud. Licenciatura en Biología Experimental. Universidad Autónoma 3 Metropolitana-Iztapalapa. México, D. F. Herbario del Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI. [email protected]. Urtica dioica L. and Urtica dioica var. angustifolia (Urticaceae) are annual plants, widely distributed in the Northern hemisphere, southern Africa and Australia. In Mexico both plants are used as tonic, astringent, antiallergenic, antianemic and to treat several dermatological and gastrointestinal infections. The purpose of this work was to evaluate the ability of U. dioica L and U. dioica var. angustifolia to inhibit the growth of bacteria. Both plants were acquired in the "Sonora market" of Mexico City, dried aerial parts of each plant were grind and macerated consecutively in hexane, dichloromethane, methanol and water at room temperature for 24 hours, solvents were removed until total dryness. The antibacterial activity was assessed by the method of resazurina, which allows to determine the minimum inhibitory concentration. Solutions of penicillin-streptomycin and dimethyl sulfoxide were used as positive and negative controls, respectively. Doses from 0.039 to 5.0 mg/mL of each extract were tested with the following bacteria; Escherichia coli, Salmonella typhi, S. typhimurium, Shigella flexneri, Proteus mirabilis, Staphylococcus aureus and Bacillus subtilis. The test was carried out three times by triplicate. Hexane and dichloromethane extracts from U. dioica L. inhibited the growth of S. typhimurium, S. flexnery and B. subtilis, at minimal dose of 0.83, 0.729 and 0.93 mg/mL, respectively. Meanwhile, hexane and dichloromethane extracts from U. dioica var. angustifolia inhibited the growth of S. typhi and S. typhimurium with minimal doses of 0.62 and 0.76 mg/mL, respectively. Extracts of U. dioica L. presented greater range of antibacterial activity. However, extracts of U. dioica var. angustifolia inhibited the development of bacteria with low doses, so it can be concluded that the latter has better antibacterial activity. 163 PHARMACOKINETICS OF PIOGLITAZONE IN A POPULATION WITH TYPE 2 DIABETES MELLITUS EXPOSED TO HIGH CONCENTRATIONS OF ARSENIC IN PEÑON BLANCO, 1 1 3 DURANGO. Terrones-Gurrola R , Vértiz-Hernández A , Ibarra-Cázares A , Ramírez Flores 2 4 1 5 1 1 E , Camacho-Luis A , Lozano- Guzmán E , Salas-Pacheco J , López-Guzmán O . Facultad 2 de Ciencias Químicas-UJED, Clínica de la Secretaria de Salud en Peñón Blanco, Dgo, 3 4 Facultad de Estudios Superiores (FES)-Zaragoza UNAM, Instituto de Nutrición-UJED, 5 Instituto de Investigaciones Científicas-UJED. It has been found a strong relationship between exposure to high concentrations of arsenic in drinking water and reduction of the expression of CYT P450, particularly the CYP3A4 isoform. Many drugs are metabolized by this isoform among which are the oral antidiabetic pioglitazone (61% CYP 3A4, 49% CYP 2C8). A negative expression of this isoform leads to poor treatment in patients with Type 2 Diabetes Mellitus, which will be exposed to inaccurate drug dose and probably ineffective or toxic. In this research we explore the hypothesis that pioglitazone pharmacokinetics observed in a population with type 2 diabetes mellitus exposed to high concentrations of arsenic is significantly different (p> 0.05) than the control population. Samples were obtained urine and plasma of a control group (n = 13) and diabetic (n = 23), which were analyzed by fluorescence spectroscopy / hydride generation and HPLC respectively. Both populations showed no significant differences (p> 0.05) in anthropometric parameters as assumed homogeneity, so neither found a difference in clinical parameters and exposure levels of both populations was found to be the same level of exposition (>0.025 ppm, NOM-127 SSA1-1998). It was found that exposure to high levels of arsenic in drinking water could be an influence for change pharmacokinetics parameters like Ka and Cl showing -1 that the values obtained from the control population are 4.8 h and 1.4 L/h respectively (p≥0.05) higher than the diabetic, also we found that the AUC0-t in the diabetic population is 1.2 higher than control (p≥0.05) suggesting a change in Bioavailability of the drug. No significant difference was found between pharmacokinetics parameter variations and its relationship with arsenic or any other factor studied in this investigation. However, we observed a marked tendency in the diabetic population suggests arsenic may eventually change its bioavailability due to damage caused in the expression of CYP 3A4. COMPARISON OF CLINICAL IMPROVEMENT PRODUCED BY CARBAMAZEPINE OR DICLOFENAC SODIUM IN PATIENTS WITH DIABETIC NEUROPATHY. Andrea Eunice Tinoco Samos, Nydia Córdova Pérez, Juan Manuel Arenas Téllez, José Luis Ordoñez Librado. Escuela de Medicina. Universidad Tominaga Nakamoto. Diabetic neuropathy (DN) is a complication with a serious impact in the physical, psychological and economic status of people who suffer it. Among the drugs used in its treatment is the carbamazepine, whose mechanism of neuropathic pain relief may be due to altered activity of sodium channels and modulation of GABA activity. In addition, nonsteroidal anti-inflammatory drugs such as diclofenac sodium have been widely used in the reduction of nociceptive pain. That’s why, in this work we conducted a comparative analysis of clinical improvement experienced by patients with diabetic neuropathy treated with diclofenac sodium or those treated with carbamazepine. For this purpose, were performed 2 groups of diabetic patients who showed signs and symptoms of ND. The first group of 30 patients, treatment was started with initial dose of carbamazepine 200 mg every 24 h. for a week, the dose was increased gradually to 200 mg every 6 h. for 10 months. The second group of 29 patients received treatment with diclofenac sodium 100 mg tablets every 12 h. for the same time. Bimonthly were evaluated clinical signs and symptoms of this complication. In our work we observed that both groups of patients had clinical improvement of pain, muscle strength and perception, but in patients treated with carbamazepine such improvements are more remarkable, showing significant difference with the group treated with diclofenac sodium. With these data we can conclude that the use of carbamazepine is more appropriate in the treatment of DN. 164 IN SILICO DRUG DESING OF OSELTAMIVIR DERIVATIVES AGAINST PANDEMIC a b INFLUENZA A H1N1(2009) Luis Esteban Tolentino Lopez , Mirko Peralta Zimic , Miguel b c c d Quiliano Meza , Verónica Briz , Mª Angeles Muñoz-Fernández , Itzia Irene Padilla Martínez, a e a a Paola Reyes Loyola , Federico Martínez Ramos, Gilberto López, José Trujillo Ferrara, José a a Correa Basurto. Laboratorio de Modelado Molecular y Bioinformática de la Escuela b Superior de Medicina Sección de Posgrados IPN, [email protected]; Bioinformatics Unit Faculty of Science and Philosophy Universidad Peruana Cayetano Heredia Av. Honorio c Delgado 430, SMP. Lima, Perú. [email protected]; Laboratorio de Inmunobiología Molecular, Hospital Universitario ―Gregorio Marañón‖ (HGUGM), Madrid, España; d e Laboratorio de Química Orgánica de UPIBI del IPN. , Laboratorio de Química Inorgánica de la ENCBIPN, México. It is know that drug resistance of neuraminidase (NA) inhibitors is due to H274Y mutation. Hence, with the aim to find new compounds with greater affinity than oseltamivir and also, to avoid the NA resistance, we have designed a set of 109 oseltamivir derivatives bearing anhydrides and aryl moities. Designed compounds were docked using NA wild type and the H274Y mutate with the aim to get a drug to treat the influenza. Protein alignment study was achieved to identify the local (at binding sites) mutations and 3-D models were builtd for recognition of potential sites purposes. Virtual screening was achieved using AutoDock 4.0.1. whereas AutoDockTools 1.5.2. and Pymol 1.3. were used to show ligand-protein interactions. Our results show that NA sequences have several mutations outside the active site while the binding site is highly conserved except for H275Y residue. Several anhydrides and aryl derivatives showed better inhibitory activity than oseltamivir. However, the binding mode is different for the former compounds whereas the latter ones show the same binding mode that oseltamivir through π-cation interactions (Arg118, 151 y 292) and π-π (Tyr406). It is important to note that some compounds reach the catalytic site. The work was supported by grants from grand ICyTDF (PIRIVE09-9) CONACYT (CB132353), Fundación Miguel Aleman A.C, PIFI-SIP-COFAA-IPN. AMINOGLYCOSIDES: THERAPEUTICS, OTOTOXICITY AND MITOCHONDRIAL 1 HYPERSENSITIVITY OF GENETIC ORIGIN. Nadia Magali Torres-Ruíz , Aurora 1 2 1 1 Castañeda-Arroyo , Omar Granados and Graciela Meza . Departamento Neuropatología 2 Molecular, Instituto de Fisiología Celular, UNAM. Departamento de Fisiología de la Nutrición. Instituto Nacional de Ciencias Médicas y Nutrición ―Salvador Zubirán‖, México D.F. Aminoglycosides (AG) such as streptomycin (STP) or gentamycin are clinically used to treat stubborn infections. In México tuberculosis patients are successfully treated with 1g/day for over 6 months. Along treatment ototoxicity is established. In young people STP damages the vestibule of the ear; in elder patients it deranges audition also. These effects are due to streptidine, an ―in vivo‖ derivative of STP produced in elder patients detected in blood by liquid chromatography. On occasion sudden deafness is established after a short treatment period, results of the presence of a single nucleotide mutation in the mitochondrial 12S rRNA gene. In this, AG produce a stereotypic conformation similar to the bacterial 16S rRNA thus inhibiting the synthesis of proteins. Many AG sensitive mutations have been described in several ethnic groups, causing sudden deafness. We started similar studies in Mexican individuals, treated or not with AG, to finding out whether similar alterations could be detected. To date in over 60 individuals analyzed we found only one case of polymorphism in a STP treated patient. Presently, we developed a simple method to identify such mitochondrial gene in a larger population to make recommendations to use an alternative treatment which do not cause ototoxicity in the mutation bearing patient. 165 NEURODEVELOPMENTAL ALTERATIONS IN A POST-MORTEM CASE OF 1 1 SCHIZOPHRENIA Totxo-Guerrero Daniel Sebastián , Herrera-de la Fuente Roberto , Reyes1 3 1 4 Pérez Mariela , Rocha L , Manzanarez-Colin Mariel Carolina , Rembao-Bojórquez Daniel , 4 4 2 Peralta-Rodríguez Brenda , Gelista-Herrera Noemí , Tristán-Agundis Ma. Francisca 1 2 Universidad Nacional Autónoma de México Hospital Psiquiátrico 'Fray Bernardino Álvarez 3 4 CINVESTAV Instituto Nacional de Neurología y Neurocirugía ―MVS‖ Schizophrenia is a severe mental disorder, characterized by profound disruptions in thinking, affecting language, perception, and the sense of self […]‖ (WHO).The distribution of the disease is universal, and early 20s the most common age of onset, with a prevalence of approximately 1%. Although the pathogenesis has not yet been determined accurately, neurodevelopmental, structural, molecular and psychosocial factors have been linked to this disorder. In the Pathology Department of the Psychiatric Hospital "Fray Bernardino Álvarez" there are 410 autopsy cases with diagnosis of mental disease, and 52 of them of schizophrenia. For this study, we chose the case of a 59 year old male patient diagnosed with chronic undifferentiated schizophrenia, with background of head trauma at 8 years old, chronic alcoholism since 20 years old, and autism with visual and auditory hallucinations of 34 years; the cause of death was upper digestive tract haemorrhage. The aim of this study is to describe the neuropathological findings in the autopsy material and their relationship with the symptoms seen. The tissues were paraffin-embedded and stained with argentaffin techniques in order to perform photonic microscopy (through a Leica device). The study of the autopsy showed pachygyria and lissencephaly in middle brain and obvious histological changes in different structures of the central nervous system, such as migration failure, cortical dysplasia (CD), bipolar neurons, and heterotopias. All the above were predominantly observed in frontal and temporal cortex and cerebellum. It is known that the onset of schizophrenia is related to structural alterations. The histopathological findings of this work resemble neurodevelopmental disorders in a case of schizophrenia. DETERMINATION OF ANTIPROLIFERATIVE ACTIVITY AND HDAC INHIBITORY ACTIVITY OF A SERIES OF ISOINDOLINES-2-SUBSTITUITED FROM ALPHAAMINOACIDS. M en C Cynthia Raquel Trejo Muñoz, Escuela Superior de Medicina del Instituto Politécnico Nacional, Dra. Teresa Mancilla Percino Dpto. de Química, CINVESTAV, Dra. Elvia Mera Jiménez ESM, IPN, Dr. José G. Trujillo Ferrara ESM, IPN, Plan de San Luis y Salvador Díaz Mirón, C.P. 11340, México, D.F. Epigenetic processes are implicated in cancer causation and progression. The acetylation status of histones regulates access of transcription factors to DNA and influences levels of gene expression. Histone deacetylase (HDAC) activity diminishes acetylation of histones, causing compaction of the DNA/histone complex. This compaction blocks gene transcription and inhibits differentiation. In this work we studied a series of isoindolines-2-susbtituted derived from a-amino acids as new HDAC inhibitors and therefore as antitumoral agents. The HDAC inhibition was determinate by a colorimetric assay in a HeLa cells nuclear extract that have a group of HDAC class I. The antiproliferative activity was evaluated in vitro by the MTT assay on HeLa cells. The results showed that all tested compounds diminish the HDAC activity in order to 98 to 62%. The proliferation assay also showed a inhibition of the proliferation from 0 to 98% in the range of concentrations of 20mM to 2mM, this can be due to the raise of histone acetylation caused by the inhibition of the HDAC. In conclusion the isoindolines-2-sustituited from a-amino acids tested have a inhibitory activity on the HDAC that can explain the antitumoral activity observed and emerge as possible therapeutic agents against cancer. 166 1 NEUROPATHOLOGY OF SCHIZOPHRENIA. Tristán-Agundis Ma. Francisca Manzanarez2 3 2 Colin Mariel Carolina , Villeda-Hernández Juana , Palacios-Escalona Sergio , Peralta3 1 3 1 Rodríguez Brenda , Castañeda-Gonzáles Carlos , Rembao-Bojórquez Daniel . Hospital 2 3 Psiquiátrico 'Fray Bernardino Álvarez', Universidad Nacional Autónoma de México, Instituto Nacional de Neurología y Neurocirugía ―Manuel Velasco Suárez‖ correo electrónico: [email protected] Schizophrenia disease is a neuropsyquiatric disease distinguished by hallucinations, delirium, thinking alterations and symptoms of cognitive dysfunction and deficit (OMS). It was described a multifactorial etiology composed by biochemical factors, genetic factors, neurodevelopment alterations and psychosocial factors. The prevalence ranges from 1.6-4.2 per 1000 inhabitants and the incidence is an average of 21.8 per 100.000. Psychiatric Hospital "Fray Bernardino Alvarez" SSA prevalence of schizophrenia is 50%. In the department of pathological anatomy there are 52 autopsy cases with diagnosis of schizophrenia, the objective of this work is to describe structural changes of the brain in the autopsy material and to set markers in order to confirm the neurodevelopmental changes, for this work we show 12 cases. The study group predominates slightly female and ages range from 14 to 69 years, of these the first psychotic episode in the majority occur between 15 and 20 years. The tissues were included in paraffin wax and cut into slides of 5 to 7µ; they were painted with Hematoxilin-Eosin, argentic stain of Bielchowsky and Fast-Blue and were exanimated with photomicroscope (Leica). The observed changes were cerebral asymmetry, cortical dysplasia, neuronal distortion, axons bifurcated, neuronophagya, branching of axons, neuronophagia and widespread demyelination. and generalized demyelinization. These histopathological changes predominate in frontotemporal lobes and cerebellum. Schizophrenia disease is the result of many events that starts with a neurodevelopment failure. It is important not only to have strategies of treatment but also prevent and give genetical advice in order to fight this ill. CHANGES IN THE VASCULAR RESPONSE TO ANGIOTENSIN II IN A MODEL OF GESTATIONAL DIABETES. Cecilia Tufiño, Santiago Villafaña, Miguel Hernández, Rosa A. Bobadilla. Departamento de Farmacología, Escuela Superior de Medicina del IPN. México, D.F. The main factor associated with development of gestational diabetes mellitus (GDM) is obesity, a condition that is link with endothelial dysfunction and insulin resistance (IR). The aim of this study was to determine whether obesity produced by DMG disrupts vascular operation. We used female Wistar rats with a weight of 225±25 g, control group received normal diet and the group of "obese" was high-calorie diet for 7 weeks (4 weeks before and during the 3 weeks of pregnancy in each case). At the end of week 4 the animals met the criteria of obesity and the DMG is found when glucose tolerance test was impaired. Using a conventional preparation of isolated rings of rat thoracic aorta, assessed the vasoconstrictor response to angiotensin II in rings with and without endothelium in the absence and presence -7 -6 of losartan (10 M) and prazosin (10 M). The results showed that the DMG does not alter the response to angiotensin II in normal conditions in rings with or without endothelium. However DMG increased response to angiotensin II in the presence of prazosin or losartan. These results suggest that DMG disrupts the operation and ability contractile responsiveness of the vessels, by a mechanism that is unmasked only when was block of AT1or -1 receptor. 167 ROLE OF GESTATIONAL DIABETES IN THE VASCULAR RESPONSE TO PHENYLEPHRINE. Cecilia Tufiño, Eulalia Fernández-Vallín, Rosa A Bobadilla. Departamento de Farmacología, Escuela Superior de Medicina del IPN. México, D.F. The main factor associated with development of gestational diabetes mellitus (GDM) is obesity. The aim of this study was to determine whether obesity produced by DMG disrupts vascular operation, evaluating the response to phenylephrine in isolated aortic rings of rats with and without endothelium. The animals were divided into control and obese groups. In turn, each group was subdivided in pregnant and non-pregnant. Obesity was achieved by submitting the animals to high-calorie diet for 7 weeks, 3 of which corresponded to pregnant condition. The group of obese pregnant met the criteria of obesity and DMG by a curve of impaired glucose tolerance. We evaluated the evolution of animal weight and systolic blood pressure by plethysmographic method as well as the vasoconstrictor response to KCl and phenylephrine in rings with and without endothelium, in the absence and presence of losartan -7 -6 (10 M) and prazosin (10 M). The DMG modified the reactivity induced by phenylephrine in the presence of prazosin and losartan both rings with endothelium and without endothelium. The results suggest that GDM alters the reactivity of vascular smooth muscle and that this alteration is intended to be modulated by the vascular endothelium. It is also possible that the DMG promotes the involvement of contractile mediators of endothelial source. NEUROPROTECTIVE EFECT OF METALLOTHIONEIN II IN CEREBRAL ISCHEMIA IN A MODEL OF MIDDLE CEREBRAL ARTERY OCLUSSION (MCAo) WITH REPERFUSION IN 1 2 3 2 RATS Vacio Adame Martha Patricia , Díaz Ruíz Araceli , Ortiz Plata Alma , Ríos Catañeda 1 1 Camilo, Monroy Noyola Antonio . Laboratorio de Neuroprotección, Facultad de Farmacia, 2 3 UAEM Cuernavaca, Morelos. México. Departamento de Neuroquímica, Departamento de Patología Experimental, Instituto Nacional de Neurología y Neurocirugía, México, D.F. Cerebral ischemia is characterized by a progressive neurological deficit oxygen and glucose that induced neuronal death. The excitotoxicity, oxidative stress, inflammation and apoptosis are the main injury mechanism in this disease. Metallothioneins (MTs) are metalloproteins with high content of cysteines. Neurochemical studies have been shown that MT II decrease cerebral injury acting as a neuroprotective agent in encephalomyelitis, traumatic cord and brain injury and other diseases with oxidative stress. In this study, we evaluated the neuroprotective effect of metallothionein II in a model of middle cerebral artery occlusion (MCAo) of cerebral ischemia and reperfusion in rats. After two hours ischemia, the animals were reperfused. Two doses of 10μg/Kg of MT II at half and eight hours were administrated i.p. after occlusion. Neurological and behavioral deficit was evaluated at 2, 24, 48, 72 and 96 hours using Longa and Capdeville scoring scales. Animals from the MT II treated group showed a statistically significant (p<0.05) reduction of neurological deficit (54%) at 96 hours after occlusion, in comparison with a control-group that showed neurological deficit using Capdeville scoring scale. This neuroprotector effect will be correlated with histopatological and inmunohistochemical MT II studies. 168 BENEFICIAL EFFECTS ON GLUCOSE HOMEOSTASIS AFTER ORAL ADMINISTRATION OF MORINDA PANAMENSIS IN NORMOGLYCEMIC RATS. Vargas-Castillo Ariana 1 1 2 Elizabeth , Castillo-Kauil Alejandro , Lara-Riegos Julio César , 1 Ortiz-Andrade Rolffy Rubén Morinda panamensis Seem has been widely used for medicinal purposes in Yucatan, Mexico. Because of this species have high similitude in its morphological features with Morinda citrifolia Linn (noni), leaves have been used as medicinal alternative treatment for diabetes. In this context, there is not enough scientific evidence that support and validate its medicinal use. For this, it was thought to perform a study to assess hypoglycemic and antihyperglycemic effect exerted by hydroalcoholic leaves extract (HEMp) on animal models applying Oral Glucose Tolerance Tests (OGTT) after acute and subchronic oral treatment. Whole animals from the short-term and long-term assay were fasted overnight previous the oral administration of test samples. Then, it was performed an OGTT using glucose (2 g/kg) as substrate. The results showed that doses of 50, 100, 200 and 400 mg/kg of HEMp exerted an antihyperglycemic effect in a dose-independent manner, supported by the decrease in percentage value of glucose variation (%GV) compared with the vehicle-treated group. At the end of each OGTT, a dose-independent hypoglycemic effect was noticed resulting from the reduced plasma glucose concentration. This behavior was similar to the antihyperglycemic drug acarbose. Moreover, daily dose of 400 mg/kg administered during a 16-day trial, maintained over the time both effects observed during the acute experiment in every OGTT performed weekly, this dose also caused a decrease in plasma lipid levels. Hence, these results can establish that the HEMp exerts beneficial effects on plasma glucose homeostasis in both acute and subchronic tests. This allows proposing M. panamensis as a suitable candidate for further pharmacological tests using in vivo diabetic models with the aim of establishing the scientific basis for the development of a phytopharmaceutical product based on a standardized extract of this species. HEIMIA SALICIFOLIA CONTAINS ALKALOIDS WITH VASORELAXANT EFFECT Vázquez-Cruz B, Guzmán-Hernández E, Avila-Acevedo JG, Segura-Cobos D. Facultad de Estudios Superiores Iztacala. UNAM. Tlalnepantla Estado de México. MEXICO. We found that the chloroform extract (CLE) from Heimia salicifolia (HBK) Link, (Lithraceae), decreased the systolic blood pressure in normotensive and hypertensive rats. Aim: Isolate the compounds with activity vasorelaxant from HS. The CLE was concentrated in vacuum and separated by column and thin layer chromatographic; four alkaloids were separated. The alkaloid 3 showed vasorelaxant effect and its chemical structure was determined by 1 spectroscopic means. The H NMR spectrum of alkaloid 3 showed similar signals as the alkaloid lytrine. The relaxant effect of lytrine was studied on the mesenteric vascular bed (MVB) from male Wistar rat normotensive (6-8) precontracted with phenylephrine (Phen10 5 -5 -5 M) in absence and presence of the next inhibitors: L-NAME (10 M), wortmanine (10 M), -5 -5 -5 methylene blue (10 M), atropine (10 M) and difenhydramine (10 M). The MVB was O suspended in a water jacketed bath at 37 C, perfused at constant flow (8 mL/min) with Krebs solution bubbled with 95% O2 and 5% CO2, pH 7.4. Dose-response curve were constructed for: acetylcholine (20-80µg), histamine (20-80µg), and lytrine (20-80µg). Results: The perfusion pressure (PP) was constant (80 1.2 mmHg). The maximum effect of lytrine was obtained with 80µg (302.5mmHg), the similar manner as acetylcholine. The PP was reduced in presence of: methylene (72 mmHg), Wortmanine (1.62 mmHg), L-NAME (8.52 mmHg) and atropine (52 mmHg). Difenhydramine did not change the PP (302mmHg). The vasorelaxante effect of lytrine is dependent of the liberation of NO, by binds whit muscarinic receptor. This results help to explain its effects on the pressure blood. Supported by CONACYT 52565 169 IN VITRO DELIVERY STUDY OF DICLOFENAC AND A NATURAL SESQUITERPENE (C15H18O2) FORMULATED IN A NANOESTRUCTURED ANHYDRA EMULSION Vázquez 1 1,4 2,4 3 1 1 ML Calpena AC , García ML ,Garduño ML ,Flórez P Department of Pharmacy and Pharmaceutical Technology, Phaculty of Pharmacy, University of Barcelona, Spain. 2 Department of Physical Chemistry. Faculty of Pharmacy, University of Barcelona, Spain 3 Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos 3 Nanoscience and Nanonotechnology Institute, University of Barcelona. Nowadays, in the treatment of inflammation are used drugs steroidal (cortico steroids) and non steroidal drugs (NSAIDs). After the identification of the enzyme COX-2, have been described more than 500 COX-2 inhibitors, depending on their chemical structure, NSAIDs inhibit both COX-1 and COX-2 in different degrees. An alternative treatment for avoid side effects could be developed a nanoemulsion applied directly onto the affected area. Nanoemulsions are kinetically stable dispersions of oil and water, forming transparent and translucent systems, with a droplet size around 100 nm. Several studies have been conducted in order to demonstrate the good potencial for transdermal drug delivery formulated in a nanoemulsions. A delivery experiment was conducted in order to see the antiinflamatories release from an anhydrous nanoemulsion with Plurol oleique®, Labrasol ®, Labrafac® and propylenglycol, prepared by lab scale sonication. These formulations presents a droplet size for diclofenac of 170.76 nm and for sesquiterpene nanoemulsion of 61.91nm, with a polidispersity less than 0.3. The study was carried out using membrane dialysis, with vertical Franz diffusion cells of 1.6 cm2. The receptor phase was ethanol:water (7:3), under temperature of 32 ± 1ºC. Samples were taken at fixed times during 118 hours. The concentrations of each sample were obtained by High Performance Liquid Chromatography (HPLC). Different release kinetic models was evaluated in order to understand the mechanism of drug release. The results obtained show that the model to describe the drug release of the diclofenac and a natural sesquiterpene is a Korsmeyer-Peppas equation (a= 50.90, R=0.9455 and a= 85.90, R=0.9921 respectively). These results predict a sustained release that allows effective and safe release. DOCKING STUDIES OF PHENOL DERIVATIVES AS INHIBITORS OF ANGIOTENSIN 1 1 1 CONVERTING ENZYME (ACE). Víctor H. Vázquez , Marco A. Alemán , Víctor H. Abrego , 1 1 1 1 Josue Acuña , Ana Ma. Velázquez , Luisa Martínez , Brígida Camacho , Rafael López 2 1 1 Castañares , Enrique Angeles . Laboratorio de Química Medicinal, Laboratorio de Farmacología del Miocardio, FES Cuautitlán, Universidad Nacional Autónoma de México, 2 Campo 1 Estado de México, México CP 54740. Facultad de Química, Universidad Autónoma del Estado de México ACE inhibitors are used for controlling blood pressure, treating heart failure, preventing strokes, and preventing kidney damage in people with hypertension or diabetes. Our group, has developed a group of compounds with an antihypertensive effect named ―LQM family‖, they are subdivided in morpholinic, thiomorpholinic and piperidinic compounds all of them are phenol derivatives with blood vessel dilatator activity. All these compounds showed a significant blood pressure reduction during a in vivo study, however the in silico experiments aim is to determinate the molecule which has the most important antihypertensive effect and to develop more efficient molecules through a screening of the reported structures. We used a Silicon Graphics Octane 2 TM workstation, Sybyl Tripos as software and MacPro Quad-Core Intel Xeon workstation with the Molecular Operating Enviroment (MOE) software, the 1UZF structure (ACE) obtained from RSCB Protein Data Bank , the quality protein pocket was checked up with the whatif-check program and the active site was confirmed by the site-finder command from MOE. The LQM’s family structures were modeled with the molecule builder from MOE. The docking studies of LQM compounds and ACE were made with the Dock simulation command from MOE, first to elucidate the most possible binding sites with a rigid-flexible (R-F) docking, and the most favorable positions were further submitted to a flexible-flexible (F-F) docking using the surrounding water molecules in the pocket and the protonation for the pocket was performed with the protonate 3D molecule to evaluate the most stable position and interactions between all the LQM compounds and ACE. Our thanks to PAPIIT/UNAM Projects No IN203609, IN207705, by partially supporting this work. 170 ANTIMICROBIAL SCREENING OF JUSTICIA SPICIGERA SCHLTDL. Vega-Avila E*, Tapia-Aguilar R, González-Gutiérrez AM, Ramírez-Cruz A, Ramírez J, Velasco-Lezama, R. Departamento de Ciencias de la Salud. Universidad Autónoma Metropolitana. Unidad Iztapalapa. Mexico, D.F. ([email protected]). Justicia spicigera (muicle) is a native Mexican plant that has been reported since XVI Century by Francisco Hernandez as medicinal plant to treat dysentery, gonorrhea, scabies, fever and uterine bleeding. J. spicigera is still used for medicinal purposes in the treatment of several illnesses. The aim of this work was to evaluate the antimicrobial activity of methanol, water and sodium bicarbonate extracts from the whole plant employing two methods. The extracts were assessed for antimicrobial activity by the Reasuring assay using Escherichia coli, Salmonella thyphimurium, Shigela flexneri, Salmonella thypi, Proteus mirabilis, Staphylococcus aureus and Bacillus subtilis. The results were expressed as Minimal Inhibitory Concentration (MIC). A Penicillin- streptomycin mixture was used as positive control. Both methanol extracts preparation showed the best antimicrobial activity and had effect on all strain bacterial tested. Also, they had the best antibacterial effect on Salmonella thypi (MIC= 0.625 mg/ml). Both extracts had a MIC of 1.25 mg/ml to S. aureus, S. thyphimurium and S.flexneri. The effect of Justicia spicigera on S. flexneri cultures supports one of its ethnomedical uses, this is to treat dysentery. ANTICONVULSANT DRUGS, OXIDATIVE STRESS AND NITRIC OXIDE. VEGA1 2 1 1 RASGADO, L. , CEBALLOS-REYES G. AND VEGA-DIAZ, F DEPARTMENT OF 2 BIOCHEMISTRY, NATIONAL SCHOOL OF BIOLOGICAL SCIENCES, I.P.N., MEXICO SUPERIOR SCHOOL OF MEDICINE, I.P.N., MEXICO Nitric Oxide (NO) is synthesized from L-Arginine (L-Arg) by three oxide synthase (NOS) isoforms: endothelial (eNOS), neuronal NOS (nNOS) and inducible (iNOS). As a free radical, NO may cause oxidative stress, which is emerging as an important mechanism in the etiology of seizure-induced neuronal death. Besides, NO is considered to play a fundamental role in the genesis and the spreading of epileptiform hyperactivity, although is not clearly understood if it is proconvulsant or anticonvulsant. Here we investigated the role of NO in seizures mechanism through oxidative stress generation by studying the effect of different anticonvulsant drugs such as amino oxiacetic acid (AAOA), Valproate (VALP), diazepam (DIAZ) and Gabapentine (GPTINA) on oxidative stress in mice brains, estimated as free carbonyls (Dalle and Rossi method), but also on NO levels (Indirect method based on Griess reaction) on muse brain. Results show that, except by AAOA, in forebrain anticonvulsants didn’t affect significantly or decreased free carbonyls, but were capable to reverse the oxidative stress that convulsions induced by pentilenetetrazole (PTZ) produced. Similar effects are exerted by anticonvulsants on NO, since all anticonvulsant diminished its level (except by VALP) and counteracted the increase on NO generated by PTZ. Decrease on oxidative stress produced by anticonvulsants was observed specially in hippocampus (HI), and cortex (CX), followed by a decrease on NO. Anticonvulsants also reversed PTZ effects on oxidative stress and NO (except by VALP) on HI and CX, but PTZ caused a decrease on NO. This could be explained since PTZ caused an increase on eNOS but a decrease on nNOS expression in HI. Since used drugs are related with GABA levels, results suggest that seizures generated by alterations in GABAergic system produce oxidative stress caused by NO, which can be reversed by anticonvulsants. Described effects depend on brain region studied and NOS isoforms affected. 171 EFFECT OF SEVERAL DOSES OF STREPTOZOTOCIN ON BLOOD SUGAR IN MALE a b a c a a CD1 MICE. J. Ventura , C.N. Aguilar , R. Ramos , E. Campos y F. Alarcón Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad b Autónoma Metropolitana-Iztapalapa, México D.F. Departamento de Investigación en c Alimentos, Universidad Autónoma de Coahuila, Saltillo, Coahuila, México. Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México D. F. Streptozotocin (STZ) is used to induce experimental diabetes in rodents. However, nowadays there is a controversy about if STZ induces diabetes similar to a type 1 or 2 diabetic. In this research we proved that grade of the STZ-induced hyperglycemia in male CD1 mice depends of the administered doses. A single injection of high doses (130 or 150 mg/Kg body weight) or multiple injections (2,3,4 or 5) of a low dose (40 mg/Kg body weight) of STZ were administered intraperitoneally in non-fasted mice, blood glucose and body weight were measured during 21 days for high doses and 21 and 28 days for low dose. At third day, high doses produced hyperglycemia and body weight lost in comparison to mice without STZ, however unstable hyperglycemias and several deaths were observed during the treatment. On the other hand, hyperglycemia and body weight lost were found with three or more injection of STZ at 21 days, whereas 4 and 5 injections produced severe hyperglycemia but deaths did not observe. Mild hyperglycemias (250-450 mg/dL) were experimented at 28 day with three injections of STZ. Therefore we concluded that a high dose of STZ produces severe hyperglycemia in mice similar to type 1 diabetic, and three administrations of STZ induce mild hyperglycemia in mice similar to type 2 diabetic. EFFECTS OF IMPLANTATION OF TIO2-DA COMPLEX IN THE CAUDATE NUCLEUS ATTENUATES MOTOR ABNORMALITIES IN THE 6-HYDROXYDOPAMINE MODEL OF 1 1 1 HEMI-PARKINSONISM P. Vergara-Aragon , L.E. Domínguez-Marrufo , P. Ibarra-Guerrero , 2 2 2 H. Hernández-Ramírez, B. Hernandez-Tellez , I.E. Lopez-Martínez , I. Sanchez-Cervantes , 2 3 3 1 A Zepeda-Rodríguez , J. A. Garcia-Macedo , G. Valverde-Aguilar . Physiology Department 2 and Cellular and Tisular Biology Department, Faculty of Medicine, UNAM.04510 México. 3 4 Solid State Department and Condensed Department, Physics Institute, UNAM México. D. F. 04510 Dopaminergic functional recovery following controlled release of dopamine from biodegradable polymer matrices implanted in the caudate nucleus was investigated in a hemiparkinsonian animal model. Significant dopamine depletion in the caudate ipsilateral to the side of implantation was observed in animals unilaterally infused with 6-hydroxydopamine (6-OHDA) in the substantia nigra. These animals displayed apomorphine-induced contralateral rotational behavior, when examined on the 14th day after lesion. Implantation of a controlled release delivery system (amorphous or anatasa) containing dopamine in the caudate on the 5 the 14th day significantly abolished the apomorphine-induced contralateral rotational behavior in these animals. The recovery with anatasa reservories with dopamine was visible from first day of treatment with TiO2-DA, until 180 days after implantation. The present results indicate that dopamine released from the polymer matrices alleviates behavioral bias in experimental hemiparkinsonism, implying use of such technologies as an alternative method for the treatment of Parkinson’s disease. Support Contributed By: DGAPA IN-223809 172 BIOLOGICAL ACTIVITY OF ORGANOMETALLICS CUPRUM COMPLEXES ON MDA-MB 1 1 1 231, HELA AND PC-3 CELLS. Rebeca Vilchis M ., Daniel Escutia C ., Blanca E. Pérez , R., 1 1 1 1 1 A. Romero R ., V.H. Abrego R. , V.H. Vázquez , Ma. Velázquez S ., E. Angeles , Cynthia 2 Ordaz Pichardo . 1.- Laboratorio de Química Medicinal, Departamento de C. Químicas, FES Cuautitlán, Universidad Nacional Autónoma de México2.-Laboratorio de Biología Celular y Productos Naturales de la Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional Millions of persons in the world are living with a diagnosis of cancer. Many researches in different institutions and pharmaceuticals companies, are studying this disease and the possible causes, screening tests, symptoms, diagnosis, and treatment and they are learning more about what causes cancer, and how it grows and progresses, so in addition they are looking for new and better ways to prevent, detect, and treat it. In this work a s a part of Drug Design Research, we present the advances of a discovery of new organometallic compounds as alternative in the treatment of some kind cancer, as mama (MDA-MB 231), cervical (HeLa), and prostate (PC-3) cancer. Those compounds were designed and synthetized as phenol derivatives which had a reaction with Cu2+, in order to obtain cuprum complexes named LQM 403, 405 and 406 respectively . They were characterized using infrared, Nuclear Magnetic Resonance. The complexes were tested on MDA-MB 231, HeLa and PC-3 cancer cells, using MTT and VC techniques, taxol (paclitaxel) as positive control and lymphocytes as normal cells. The results will be discussed widely during the meeting. Acknowledgments: Our thanks to PAPIIT/UNAM Projects No IN203609, IN207705, by partially support this work. We would like to thank C. Barajas, F. Sotres, Rosa María Valadéz, D. Jiménez, M. HernándezDuarte for their skillful technical assistance PRE-TRANSPLANT MYCOPHENOLATE MOFETIL PHARMACOKINETICS IN MEXICAN 1 2 1 1 1 CHILDREN Villa M , González R , García-Roca P , Hernández AM , Ortiz L , Castañeda2 1 Hernández G , Medeiros M . Protocol HIM/2011/013 Nefrología, Hospital Infantil de México Federico Gómez; Laboratorio de Farmacología CINVESTAV IPN. Mycophenolate mofetil (MMF) is a immunosuppresive pro-drug frequently used to prevent renal graft rejection, it is hydrolyzed by esterases in the gastrointestinal tract, blood and liver to obtain the active drug mycophenolic acid (MPA), which is metabolized by UGT1A9.There is high interpatent variation in MPA pharmacokinetics, AUC is used for therapeutic drug monitring in adults, recommended levels are 30-60g*h/L. The main adverse effects are leukopenia and gastrointestinal complications. The aim of the study was to determine MPA pharmacokinetics in children in the waiting list of renal allograft in order to predict MMF dose requirements. Material and Methods: End stage renal disease children in the waiting list for renal allograft were invited to participate in the study. A nine-point pharmacokinetic profile 2 was performed, all of them received a single dose (600mg/m SC) of MMF at time 0. MPA was measured by HPLC. The AUC0-12h was estimated by the trapezoidal rule. We used the program PhoenixTM Win Non Lin Version 6.0 (pharsight Corporation, St. Louis, MO, USA). Results: 10 children were included, mean age was 13.65 years. The median AUC0-12h was 20.3 g*h/L (range 0-71), median Cmax 0.7 (range 0-2 g/mL).Two children (20%) had no detectable levels of MPA after a single MMF dose, other two patients had AUC >30g*h/mL. One patient had abdominal pain 1h after the MMF dose. Conclusions: 20% of the patients had no MPA detectable levels after a single MMF dose, those patientse should receive a higher MMF dosing since the begining of the transplant to avoid acute rejection. 20% of our patients had AUC0-12h higher than the recommended value after a single MMF dose, those patients should receive lower MMF dose since the begining of the transplant to avoid adverse events. UGT1A9 gene polymorphisms remain to be studied in our patients, since they could explain the differences in bioavailability. 173 CELLULAR DAMAGE MARKERS IN THE TEMPORAL LOBE OF A PATIENT WITH 1 2 DYKE-DAVIDOFF-MASSON SYNDROME Villeda-Hernández J ., Alonso-Vanegas MA , 3 1 2 Osorio-Rico L . Laboratorio de Neuropatología Experimental , Servicio de Neurocirugía , 3 Departamento de Neuroquímica , Instituto Nacional de Neurología y Neurocirugía, México, Distrito Federal, México. Dyke-Davidoff-Masson Syndrome is characterized by various symptoms related to hemiatrophy of the cerebrum and the hypertrophy of the ipsilateral, calvarium and paranasal. Surgical specimen from patient with chronic pharmaco-resistant temporal lobe epilepsy. The epileptic region was localized to the right temporal lobe, and an extensive surgical removal of the temporal neocortex plus amygdale (A) and hippocampus (HP) was performed. The surgical specimens were obtained and immediately frozen in liquid nitrogen and stored at -75 °C for biochemical studies. The surgical specimens for histopathological evaluation were immersed and fixed in freshly prepared to 4% paraformaldehido. In this study the levels of neurotransmitters were highest in the hippocampus compared to the temporal neocortex (T1, T2, and T3). In amygdala, only GABA was found whereas other aminoacids were absent. We found marked dislamination in all areas of the cortex, neuronal loss, amylaceous bodies, and neuronal cytomegaly with cytoskeletal disorganization containing dense fibrillar cytoplasmic aggregates, nodular heterotopias, dysplastic and large neurons with high Nissl staining, intermixed with balloon cells with atypical nuclei, often with binucleation, and abundant glassy eosinophilic cytoplasm, positive immunoreactives cells with nestin, vimentin, and enhanced expression of the astrocytes were observed in all brain regions studied. This patient´s syndrome should be considered as a post-infectious event which caused hemiparesis and later recurrent zeisures. Higher expression of nestin has been observed in proliferative neuronal cells, the expression in astrocytes may mainly reflect an early response of these cells to injury. Nestin may play a role in protecting the brain from injury. It has been proposed that re-expression of embryonic genes by mature gill cells is associated with morphological plasticity. CAFFEINE-INDUCED VASCULAR SMOOTH MUSCLE CONTRACTION IS MODULATED 1,2 1 BY 17Β-ESTRADIOL IN RAT AORTA. Villegas Bedolla, J.C. ; Godínez Hernández D. ; 1 1 2 Urquiza Marín H. ; Nateras Marín, B. ; Hernández Rebollar Madeline ; Valencia Hernández 2 1 I . Instituto de Investigaciones Químico-Biológicas de la U.M.S.N.H., Morelia, Mich.; 2 Facultad de Químico-Farmacobiología de la U.M.S.N.H., Tzintzuntzan Morelia Mich.; y 3 Escuela Superior de Medicina del IPN, In a wide variety of cells, agonists such as neurotransmitters, hormones, or growth factors trigger cellular responses through an increase of the cytosolic Ca2+ concentration. This increase can result from both Ca2+ release from intracellular Ca2+ stores and Ca2+ influx through plasma membrane channels. For example in rat aorta noradrenaline induced a biphasic contractile response in Ca2+-free medium through two different intracellular pools of Ca 2+, one of them common to caffeine. The empty of this pool of Ca2+ are related with a mechanism of entry of the cation from extracellular space in order to refilling such stores and to promote contraction. 2+ Estroge -estradiol 2+ reduced the increase of intracellular Ca by blocking voltage dependent channels. However, there -estradiol modify the mechanisms of Ca2+ sensitive to -estradiol controls the caffeine-sensitive pool of Ca2+. Rat aortic rings from sham and ovariectomized rats were employed, the last were divided in two groups and one of them was treated with vehicle and the -estradiol for 5 days postovariectomy. Rat aortic contractions to caffeine (25 mM) in a Ca2+ free medium were induced. Ovariectomy induced a reduction in the caffeine-promoted contractio -estradiol restores the ovariectomy-induced reduction of the contractility to caffeine. In conclusion estrogens control the caffeine contraction probably by reducing the release of Ca2+ from intracellular pools sensitive to the xantine. 174 MORPHO-HISTOLOGICAL CHANGES IN MALE RAT GONADS PERINATALLY TREATED WITH TAMOXIFÉN AND COUMESTROL. Zamora Gutiérrez Diana, Rosales Torres Ana María, Vergara Onofre Marcela, Herrera Gutiérrez Héctor, Ávalos Rodríguez Alejandro. Departamento de producción agrícola y animal. Laboratorio de bioquímica de la reproducción. UAM-X. Sexual dimorphism is an essential process for reproduction and preservation of species. Sexual differentiation in mammals involves several anatomical, physiological and behavioral differences include morphological primary and secondary sexual characteristics, differences in reproductive and nonreproductive behaviors as well as structural and ultrastructural differences in central nervous system (CNS). Sexual differentiation is a process regulated by multiple factors, among which are the hormones secreted by the gonads during critical periods of development. The administration of hormones in the perinatal period permanently impairs sexual behavior of individuals. In rats, administration of Tamoxifen (Tx), a drug with anti-estrogenic actions, is capable of desmasculinizar and feminize the sexual behavior of males (Morales, 2002). In the present study evaluated 32 male rats were randomly divided randomly into 4 treatments: T1: Control (20 µl of vehicle), T2: Coumestrol (100 µg of Coumestrol in 20 µl of vehicle), T3: Tamoxifen (200 µg of Tamoxifen in 20 µl of vehicle), T4: 100 µg of Coumestrol, 200 µg of Tamoxifen in 40 µl of vehicle. At the time of birth was applied for treatment. The rats were sacrificed at 120 days at which time the following variables were measured: weight at birth, weight each week and sexual behavior. After sacrifice the rats was extracted from hypothalamus and obtaining testes (left and right). Statistical analysis was performed as an Analysis of Variance (ANOVA) followed by Tukey test to compare differences between treatments. Difference was statistically significant when value (p <0.05). Statistical analysis was performed using the statistical package Microstat. The results obtained in this work with respect to the body weight of each group was not statistically significant differences (p <0.05). Regarding sexual behavior patterns, weight and measurements of gonads, differences were statistically significant (p <0.05) between each treatment group. For the weight of hypothalamus found no statistically significant difference between each group. Therefore we can conclude that Coumestrol is unable to reverse the effects of Tamoxifen, however applied for this same mark for the purposes of this antiestrogen. INSULIN EFFECTS ON ISOLATION CALLS OF INFANT GUINEA PIGS. Zarco de 1 2 3 1 Coronado I .*, Coronado Zarco I.A ., Coronado Zarco R. , Departamento de Fisiología, 2 Facultad de Medicina. Universidad Nacional Autónoma de México. A.P. 70250, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes SSA y Centro Medico Nacional 20 3 de Noviembre ISSSTE, Instituto Nacional de la Rehabilitación SSA México, D.F. ([email protected]) It is well known that insulin induces hypoglycemia, an extensive derangement of body energy state. The present experiment examined the effect of this substance on the vocalizations of the preweaning guinea pigs when they are separated from their mothers. The 10-13 days old pigmented guinea pigs (Cavia porcellus) were kept with their mothers housed in a polycarbonate maternity cage. The day before the experiments glycemia was determined in all the animals. The experimental animals were injected with insulin (4 IU/kg ip) in saline solution (2ml/kg). Control animals were injected with the vehicle. The animals were returned with their mother. One hour later each pup was introduced in a polycarbonate cage (34x23x14 cm) during 6 minutes without its mother in a sound isolated room. During this time the experiments were videotaped (Sony HandycamTR305). The vocalizations were digitalized using Cool Edit 2000 software. The statistical analysis was made using Friedman test to compare the duration of the vocalizations. At the end of the recordings blood sugar was determined again and a sugar solution ABBOT 50% (1ml/kg) was administered to restore normal glycemia levels. During the isolation the experimental animals showed long vocalizations than never were presented by the control animals. The duration of the longest vocalizations in the control animals was 21770.24ms and in experimental animals 642447.47 (p=0.006). In conclusions the results suggest that hypoglycemia is also a stressful condition that intensifies communication signals produced by the pups during the isolation. 175 EFFECTS OF BEE PRODUCTS ON OPEN FIELD, LIPID PEROXIDATION LEVELS AND PERFORMANCE OF SEIZURES KINDLED BY THE ADMINISTRATION OF 1 1 PENTYLENETETRAZOL IN RATS. N. ZARRAGA-GALINDO , P. VERGARA-ARAGON , P. 1 1 1 IBARRA-GUERRERO , L. E. DOMÍNGUEZ-MARRUFO , H. HERNÁNDEZ-RAMÍREZ , B 2 2 2 HERNANDEZ-TELLEZ , I.E. LOPEZ MARTÍNEZ , I. SANCHEZ-CERVANTES . 1 Physiology 2 Department and Cellular and Tisular Biology Department, Faculty of Medicine, UNAM.04510 3 México. The repeated administration of convulsant dose of pentylenetetrazol (PTZ) is known to produce chemical kindling in rats. The present work was realized to determine the effects of an alimentary compliment based on bee products (pollen, honey, royal jelly, bee wax and bee queen larvae) on the seizure performance, locomotor activity, and lipid peroxidation levels on cerebrospinal fluid (CSF) after different postkindling periods comparing to the controls. Design: 32 Wistar male rats were used. Animals were randomly divided into 4 groups of 8 rats each: 1) Saline group; 2) Bee product group; 3) PTZ group 4) PTZ plus bee product treatment. Open Field Test (latency, frequency, duration of seizure, number of squares crossed, trajectory of locomotion, rearing, number of fecal boli were analized) and the lipid peroxidation levels (LPO) were determined. Results: Oral administration of BP before PTZ injection caused a significantly increased the time of seizure apparition, the duration of seizures was diminished, frequency of seizures decreased, C and LPO decreased. In the Open Field test the control, BP and PTZ plus BP groups showed an increase in the number of squares crossed, an increased in rearing counts, and a decreased in fecal boli. In contrast PTZ group showed high peroxidation levels in CSF, immobilization on open field test all time and increasing of death during seizure. In conclusion, the results of the present study suggest the possible neuroprotective action of bee products against PTZ-induced kindling. This work was supported by DGAPA-IN223809. EFFECTS OF MGLUR5 ANTAGONIST MTEP ON HIPPOCAMPAL EPILEPTIC 1-2 1 AFTERDISCHARGES IN IMMATURE RATS. Cecilia Zavala-Tecuapetla , Pavel Mares , 1 Hana Kubova . Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, 1 Czech Republic Department of Pharmacobiology, Research and Advanced Studies Center, 2 Mexico Modulation of metabotropic glutamate receptors represents an interesting new approach for the treatment of epilepsy. Numerous studies suggest that functional blockade of group 1 (mGlu1 or mGlu5) receptors produce anticonvulsant action in different rodent models. The aim of the present study was to characterize the effects of selective mGluR5 antagonist MTEP ([(2-methyl-1,3thiazol-4-yl) ethynyl] pyridine) on epileptic afterdischarges (ADs) elicited in immature rats. Stimulation electrode was implanted into dorsal right hippocampus and recording electrode into the left hippocampus, in 12- 18- and 25-day old Wistar rats. Moreover, one cortical electrode was placed epidurally over frontal area. Stimulation (biphasic electrical pulses with duration of 1 ms and frequency 50 Hz, during 2 s) was applied six-times repeatedly in 10-min intervals. The threshold intensity was determined by increasingly higher values (from 0.3 to 4.0 mA) and just suprathreshold intensity was used in the experiment. Electroencephalograpic (EEG) activity was recorded and duration of ADs as well as number of WDS accompanying ADs was evaluated. The first control AD was longer in 12-day-old than in older animals, number of WDS was lower in 12than in 18-day-old rats. MTEP (20 and 40 mg/kg) administered intraperitoneally 5 min after the first AD was able to significantly shorten hippocampal and cortical ADs. This effect was best expressed in 12-day-old rats; both doses led to significant shortening not only of the second but also subsequent ADs. The number of WDS was decreased mainly by the 40-mg/kg dose in 12day-old rats. Eighteen- and 25- day-old rats exhibited a decrease of AD duration after the higher dose of MTEP. The number of WDS was decreased only by the 20-mg/kg dose in 18-day-old rats and not change was observed in 25- day-old rats. Effects of MTEP on hippocampal epileptic seizures are age-dependent with a maximum at postnatal day 12. This study was supported by a grant No.305/06/1188 of the Grant Agency of the Czech Republic, by research projects LC-554 and AV0Z50110905 and by CONACYT. 176 EFFECT OF CHRONIC SUGAR INTAKE ON MALNOURISHMENT-INDUCED BEHAVIOURAL, METABOLIC AND CARDIOVASCULAR ADAPTATION. Alejandro Vargas-Olmos, Esteban Reyes-Antunez, Rafael Ramírez-Solares, Lorena Mendiola-Alcaráz, Ricardo Ramírez-Oseguera and María Dolores Ramírez-González. Fourth Year Medical Students, Department of Pharmacology, School of Medicine, UNAM. Malnourishment was induced by food restriction (FR: 9g/day/rat) of pregnant Wistar rats until weaning of the litter. After weaning, groups of 3 male rats were kept on FR (MAL). All animals were housed in satandard conditions. Control rats received rat chow and water ad libitum (CTL). Chronic sugar intake in the drinking water (30%) was initiated after parturition (SUG) in either CTL and MAL. A control group of MAL received regular tap water. Food and water intake were monitored daily. Blood pressure (BP), heart rate (HR), glycemia (GLY), cholesterolemia (CHO), and triglyceridemia (TRG) were measured at 6, 7, 8 and 9 months of age in non-anaesthetized rats using a tail-cuff procedure and Accutrend reactive strips, respectively. Statistical and graphical analysis were done using Excell. A P value <0.05 was used to assess significance. MAL-induced hyperactivity and decrease in body weight are significantly attenuated by SUG when compared with CTL. SUG induces hypophagia in CTL, and polydipsia significantly larger in MAL than in CTL. SUG induces larger and significant increases of TRG in CTL than in MAL. There were no changes in CHO in any SUG treated groups; and only a discrete but significant increases of GLY in SUG groups. GLY to TRG conversion is significantly smaller in MAL. SUG induced significantly larger intolerance to an acute glucose load (2 g/kg/ip) in MAL when compared with CTL. Very minor GLY peaks were observed in MAL. SUG attenuates MAL-induced blunting of baroreflex response (BRE), estimated from the pulse pressure versus pulse period plots, but has no effect on BRE. VALIDATION OF AN EXPERIMENTAL METHOD TO INDUCE CHRONIC HYPERGLYCEMIA BY ONLY ONE DOSE OF STREPTOZOTOCIN (STZ) IN WISTAR RAT. 1,2 1 1 José L. Figueroa-Hernández José L. Figueroa Espitia , Gabriela Fernández Saavedra 2 2 1 Teresa Ramírez and Mariano Martínez Vázquez . Facultad de Medicina, Departamento de 2 Farmacología, Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, 04510, México, D. F. Email: [email protected]. Con apoyo del CONACYT STZ has been widely used to induce, in rat and mouse, experimental diabetes mellitus (DM) type 1 o type 2 (newborn animals). There is an overlap between type 1 y 2 in several different experimental animal models, and someone of the classical models for each type cannot be sustained (Chapparro et al, 2006). Decision respect which model to utilize is determined by local resources. Most common diabetogenic STZ doses is 65 mg/kg, by IV o IP way, but several animals die (Frode and Medeiros, 2008). However, validity of such statements has been questioned (Andrade, 2005). Continuing the investigation line on plants with anti-DM use, with our own laboratory resources and environmental conditions, and by the advantages of the method, we decided to validate in fasting (12 h) Wistar rats the hyperglycemia induced by 50 mg/kg/im of STZ. After that, no glucose solution (5%) was administered; but free access to food and water was allowed; no matter what type of diabetes is induced we only used the hyperglycemia as a functional signal of damage. Results: The 3 steps reported for glycemia by STZ was reproduced: initial 1-2 days hyperglycemia; intermediate hypoglycemia by 2-3 days and sustained hyperglycemia since 5-6 day; at 7º day the anti-hyperglycemic effect of Ibervillea Lindheimeri extracts was determined. Then, rats were maintained at standard lab/conditions with free access to food and water. Periodically body weight and glycemia were measured (Accuchek sensor comfort reactive tires). Body weight increase of STZ treated rats is lower than control rats. Hyperglycemia was sustained by 6 months. Acute/chronic mortality by STZ was 2/30 and 3/28 rats, respectively. This method is useful to induce a permanent hyperglycemic state (core in human DM, responsible of complications on microcirculation: retino-nephro-pathy). Besides, is useful to determine anti-hyperglycemic effect of drugs and extract of plants. 177 WILD FLORA PRESENT IN A NEW URBAN HUMAN SETTLEMENT AT XOCHIMILCO DELEGATION IN MÉXICO CITY. *Figueroa-Hernández J.L., Fernández-Saavedra G. and Figueroa-Espitia J.L. Departamento de Farmacología, Facultad de Medicina. Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, 04510, México, D.F. (e-mail: [email protected]) The creation of Profound Drainage System at México City during 80-90’s decades of the 20th Century triggered the foundation of two new settlements in areas know since the Colonial times suffer of flooding. Agricultural practice were followed by houses construction causing the gradual loose of vegetal and animal endemic species, as well as Plants known by oral tradition for they curative use since pre- Colombian times. Objective: To identify the type of wild botanical species current present in the few remnant pieces of land where there are not houses (Barrio 18), which are actually used in Mexican herbolary and identifies them by common and scientific name. Method: several individuals of wild plants were collected at different times of the year. Photography’s in the external environmental were taken to support identification. They were presented to healers in Sonora and Xochimilco markets, at México, City, to inquire on their common names and therapeutical uses. Taxonomy and scientific name of the plants were obtained at Herbarium of Faculty of Sciences at The Universidad Nacional Autónoma de México. Further research in the scientific literature was done to confirm their medical use. Results: Seven plants currently used in traditional medicine were detected and one with poisoning dangerous effect. These observations indicate the need to revaluate and enhance the interest of the Mexican investigators in the scientific and systematic study of plants, besides the defense of nature, in ecologic, Phenologic, Phytogeography, chemical and taxonomic aspects, and the scientific determination of the curative properties of the Mexican flora. 178 179 PROGRAMS OF CONGRESS COURSES 180 181 1. Introduction to Pharmacoepidemiology. INTERACTIVE LECTURE PROFESORES: Maribel Salas, Abraham Hartzema, Chris Delaney MINIMUM NUMBER OF ATTENDEES: TEN MAXIMUN NUMBER OF ATTENDEES: NO LIMIT MIÉRCOLES 18 DE MAYO DE 14:20 A 16:20 h AUDITORIO PRINCIPAL DEL PALACIO DE LA ESCUELA DE MEDICINA TOPICS TO BE COVERED: Designs in Pharmacoepidemiology (20 min) Case report and case series (20 min) Cohort Studies (30 min) Case-Control Studies (30 min) Summary (20 min) Este sesión interactiva se realizará en ingles. No habrá traducción simultánea 2. Data Mining INTERACTIVE LECTURE PROFESORES: Maribel Salas, Abraham Hartzema MINIMUM NUMBER OF ATTENDEES: TEN MAXIMUN NUMBER OF ATTENDEES: NO LIMIT JUEVES 19 DE MAYO DE 14:20 A 16:20 h AUDITORIO PRINCIPAL DEL PALACIO DE LA ESCUELA DE MEDICINA TOPICS TO BE COVERED: Traditional Methods for signal detection Case series review for signal detection Simple analysis of larger datasets Quantitative signal detection methods: Disproportionality analysis Bayesian methodologies Evaluating data mining performance Summary Este sesión interactiva se realizará en ingles. No habrá traducción simultánea 182 3. Diseño de moléculas activas asistido por computadora Coordina: Dra. Elena Guadalupe Ramírez PROFESORES DEL CURSO: Dr. Francisco Hernández Luis y M. en C. Rubén Antonio Romo Mancillas Mínimo número de asistentes: CINCO Máximo número de asistentes: 12 Objetivos: Proporcionar los conocimientos y herramientas básicas para el uso del acoplamiento molecular (Docking) en la búsqueda de moléculas activas. MARTES 17 DE MAYO DE 14:20 – 16:20 h AULA PROV. DOS DEL PALACIO DE LA ESCUELA DE MEDICINA Sesión de conceptos básicos y acceso al PROTEIN DATA BANK. Requisitos para seleccionar la macromolécula blanco. MIÉRCOLES 18 DE MAYO DE 14:20 A 16:20 h AULA PROV. DOS DEL PALACIO DE LA ESCUELA DE MEDICINA Visualización y manipulación de la macromolécula y el ligando. Programas: PyMOL, AUTODOCK, ARGUSLAB JUEVES 19 DE MAYO DE 14:20 A 16:20 h SALA DE JUNTAS DE INVESTIGACIÓN, PALACIO DE LA ESCUELA DE MEDICINA Procedimientos de acoplamiento molecular (DOCKING) e interpretación de resultados. VIERNES 20 DE MAYO DE 14:20 A 16:20 h SALA DE JUNTAS DE INVESTIGACIÓN, PALACIO DE LA ESCUELA DE MEDICINA Resolución de un caso particular REQUIEREN TRAER COMPUTADORA PERSONAL (LAPTOP). EL LUNES 16 DE MAYO SE INSTALARÁ EN SUS EQUIPOS EL PROGRAMA QUE SE EMPLEARÁN EN LAS SIGUIENTES SESIONES . LOS PROGRAMAS SON DE APROXIMADAMENTE 100MB; POR LO QUE EL EQUIPO DEBE TENER MEMORIA RAM: A PARTIR DE 1 MB; LA CAPACIDAD DE DISCO DURO ES MÍNIMO 200 MB, CON UNA VELOCIDAD DE 2 GB. SI SE TIENE MÁS DE UN NÚCLEO ES MEJOR . LA INSERCIÓN DEL PROGRAMA PODRÁ SER POR RED Ó USB. DEBEN TRAER SU MÁQUINA EL LUNES PARA REALIZAR LA INSTALACIÓN Este curso se impartirá en español. 4. Tratamiento integral de la obesidad 183 Coordina: Dra. Bertha Prieto López, Coordinadora Departamento de Fisiología, Facultad de Medicina, UNAM de Investigación del Mínimo número de asistentes: DIEZ Máximo número de asistentes: VEINTE MARTES 17 DE MAYO DE 14:20 – 16:20 h PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA Modelo novedoso de síndrome metabólico Dra. Karla Carvajal Aguilera y Dr. Daniel Ortega Cuéllar Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría. MIÉRCOLES 18 DE MAYO DE 14:20 A 16:20 h PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA Metabolismo de hueso y síndrome metabólico Dr. Rolando Espinosa Morales. Jefe de Servicio de Reumatología. Instituto Nacional de Rehabilitación JUEVES 19 DE MAYO DE 14:20 A 16:20 h PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA Manejo bariatrico del síndrome metabólico Dr. Gonzalo Torres Villalobos Departamento de cirugía del Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. VIERNES 20 DE MAYO DE 14:20 A 16:20 h PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA Manejo dietético del síndrome metabólico Dra. Amanda Gálvez Mariscal Coordinadora del Programa Universitario de Alimentos Depto. Alimentos y Biotecnología, Facultad de Química. UNAM Este curso se impartirá en español. 5. Manejo ambulatorio del paciente diabético PROFESOR DEL CURSO: Dr. Jorge Isaac Cabrera Cortina Mínimo número de asistentes: CINCO 184 Máximo número de asistentes: VEINTE JUEVES 19 DE MAYO DE 08:00 A 12:00 h AULA MAGNA DEL PALACIO DE LA ESCUELA DE MEDICINA TEMAS A REVISAR: 1.- ¿QUE DEBO DE EVALUAR PRIMERO CLINICAMENTE EN MI PACIENTE? 2.- ¿CUALES DEBEN DE SER LOS EXAMENES DE RUTINA? 3.- LA CAPACITACION EN MI PACIENTE EN SU HIGIENE Y AUTOCUIDADO 4.- EL EJERCICIO O LA ACTIVIDAD FISICA: ¿COMO DOSIFICAR ESTOS PARAMETROS ADECUADAMENTE 5.- LA DIETA ADECUADA: BALANCE DE CALORIAS 6.- FARMACOLOGIA EN DIABETES (PARTE1): LOS MECANISMOS DE ACCION DE LOS FARMACOS ORALES Y LOS DIFERENTES TIPOS DE INSULINAS VIERNES 20 DE MAYO DE 08:00 A 12:00 h AULA 246 TEMAS A REVISAR: 7.- FARMACOLOGIA EN DIABETES (PARTE2): EL CONTROL GLICEMICO RESERVA PANCREATICA, PROTECTORES PANCREATICOS, RESISTENCIA A LA INSULINA Y LAS TERAPIAS COMBINADAS 8.- FARMACOLOGIA EN DIABETES (PARTE 3): LAS DISLIPIDEMIAS Y LA DISMINUCION DEL PROCESO INFLAMATORIO 9.- FARMACOLOGIA EN DIABETES (PARTE 4): LA HIPERTENSION ARTERIAL LA NEFROPROTECCION Y LA NEUROPROTECCION 10.- FARMACOLOGIA EN DIABETES (PARTE 5): EL EMPLEO MÁS ADECUADO DE LOS MEDICAMENTOS PARA EVITAR LOD PROCESOS INFECCIOSOS CONTRA BACTERIAS, HONGOS Y VIRUS 11.- REFERIR O NO REFERIR ¿CUANDO Y COMO? OPORTUNIDAD DE EVITAR LA INVALIDES DEL PACIENTE LA SEGUNDA 6. Ingeniería de tejidos Profesores del curso: Dr. Andrés Castell Rodríguez, Dr. Miguel Herrera Enríquez y Dra. Gabriela Piñón Zárate Mínimo número de asistentes: CINCO Máximo número de asistentes: QUINCE LUNES 16 DE MAYO DE 14:30 A 16:20 h 185 AULA PROV. DOS DEL PALACIO DE LA ESCUELA DE MEDICINA Introducción a la Ingeniería de Tejidos: 1 hora Aislamiento y caracterización de células madre. 1 hora MARTES 17 DE MAYO DE 14:30 A 16:20 h AUDITORIO PRINCIPAL DEL PALACIO DE LA ESCUELA DE MEDICINA Ingeniería de tejidos de piel 2 horas MIÉRCOLES 18 DE MAYO DE 14:30 A 16:20 h ANEXO DOS DEL PALACIO DE LA ESCUELA DE MEDICINA Aislamiento y diferenciación de células dendríticas. 2 horas VIERNES 18 DE MAYO DE 14:30 A 16:20 h AUDITORIO PRINCIPAL DEL PALACIO DE LA ESCUELA DE MEDICINA Ingeniería de tejidos de hueso y cartílago Este curso se impartirá en español 7. Diseño de un protocolo para un estudio biodisponibilidad/bioequivalencia Profesores del curso: Dra. Susana Tera Ponce y M. en C. Luis García Aguirre de Mínimo número de asistentes: CINCO Máximo número de asistentes: QUINCE LUNES 16 DE MAYO DE 2011 DE 08:00 – 13:30 h AULA MAGNA DEL PALACIO DE LA ESCUELA DE MEDICINA PRIMERA PARTE Cuota de recuperación $1000 pesos por el reconocimiento UNAM (en trámite) Temas a revisar: 1. Acercamiento a la legislación mexicana aplicada a las pruebas de intercambiabilidad y su interpretación 2. Provisiones regulatorias para los medicamentos que requieren pruebas de intercambiabilidad y fuentes de información en la COFEPRIS 3. Contenido de un protocolo clínico para estudios de biodisponibilidad/bioequivalencia acorde al modelo COFEPRIS 4. Requisitos de la COFEPRIS para la solicitud de autorización de protocolos de biodisponibilidad/bioequivalencia LUNES 16 DE MAYO DE 2011 DE 14:30 – 18:30 h PARANINFO DEL PALACIO DE LA ESCUELA DE MEDICINA SEGUNDA PARTE Cuota de recuperación $1000 pesos por el reconocimiento UNAM (en trámite) 186 Temas a revisar: 1. Consideraciones éticas y definición de los objetivos del estudio 2. Información científica y regulatoria para la elaboración de un protocolo clínico de biodisponibilidad/bioequivalencia 3. Diseño experimental y tamaño de la muestra 4. Selección de voluntarios 5. Desarrollo del estudio 6. Parámetros de seguridad y eventos adversos 7. Método bioanalítico 8. Parámetros faramcocinéticos y bioestadística 9. Documentación analítica e integración del informe final Este curso se impartirá en español 8. Taller de elaboración de Consentimiento Informado Profesora del curso: Dra. Susana Tera Ponce Mínimo número de asistentes: CINCO Máximo número de asistentes: QUINCE MARTES 16 DE MAYO DE 2011 DE 09:00 A 18:00 HORAS AULA PROV. UNO DEL PALACIO DE LA ESCUELA DE MEDICINA Cuota de recuperación $1000 pesos Temas a revisar: 1. Evaluación inicial 2. Antecedentes: autonomía 3. Proceso de elaboración del formato de Consentimiento Informado y obtención del Consentimiento Informado 4. Práctica de Autonomía 5. Ley General de Salud. Reglamento de la Ley General de Salud en materia de Investigación para la salud. Errores más frecuentes. 6. Práctica: elaboración de un Consentimiento Informado 7. Presentación del Consentimiento elaborado 8. Evaluación final Este curso se impartirá en español 9. El papel del Terapeuta en la cesación del Tabaquismo PROFESORA DEL CURSO: Dra. Marcela Oseguera Mínimo número de asistentes: CINCO Máximo número de asistentes: VEINTE MARTES 17 DE MAYO DE 2011 DE 09:00 A 14:00 h AULA 246 DEL PALACIO DE LA ESCUELA DE MEDICINA MIÉRCOLES 18 DE MAYO DE 09:00 A 14:00 h 187 Objetivo General: Adquirir conocimiento de las Técnicas de Modificación de Conducta, Terapia Cognitivo Conductual y Terapia Racional Emotiva. Instruir sobre estrategias de seguimiento a corto y largo plazo del paciente con tabaquismo 9:00-9:50 h Aplicación del Convenio Marco para el Control del Tabaco en México. Dr. Jesús Felipe González Roldan. Administración de la Región.Unión Internacional Contra La Tuberculosis y Enfermedades Respiratorias 9:50 - 10:40 h Aplicación MPOWER. Lic. Diana Calderón. Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado 10:40 - 11:00 h Receso 11:00 – 11:50 h Entrenamiento en Terapia Racional Emotiva. Mtra. Ma. Angélica Ocampo Ocampo. Jefa de la Clínica Contra Tabaquismo. Hospital General de México 11:50 -12:40 h Terapia Cognitivo Conductual (TCC). Mtro. Psic. Eduardo Cuevas Aguirre. Hospital General de México 12:40 – 13:30 h Historia de fumador. Pruebas de Tamizaje, Diagnostico en Tabaquismo y Perfil del Fumador. Psict. Esp. Adic. Tania Villa Hernández. Hospital General de México 13:30 – 14:00 h Conclusiones y clausura Este curso se impartirá en español POR CONFIRMARSE: La Administración Educativa y su relación con las ciencias de la salud PROFESORA DEL CURSO: Dra. Marcela Oseguera Mínimo número de asistentes: CINCO Máximo número de asistentes: DIEZ MIÉRCOLES 18 DE MAYO DE 09:00 A 13:00 h AULA MAGNA DEL PALACIO DE LA ESCUELA DE MEDICINA Temas a revisar I. Administración 1.1 Orígenes 1.2 Antecedentes 1.3 El proceso administrativo 1.4 Aplicaciones 188 II. La Educación en México 1.1 Evolución histórica 1.2 Actividades del sistema educativo nacional 1.3 Reforma educativa nacional ( 1971-1976) III. Antecedentes de la Educación Superior 1.1 Orígenes de la Universidad 1.2 Para qué la Universidad 1.3 Logros y alcances de la Universidad IV. Administración educativa y su relación con las Ciencias de la salud 1.1 Orígenes de la administración educativa 1.2 La enseñanza en las Ciencias de la Salud 1.3 Aplicación de la administración educativa en las Ciencias de la salud. V. Problemas actuales de la Educación Superior 1.1 En México 1.2 En América Latina 1.3 En el mundo Este curso se impartirá en español 189 ALPHABETICAL INDEX OF AUTHORS Almanza Pérez JC Abrego Reyes VH Alonso González SA Aburto Amar R Alonso Vanegas MA Acosta Gutierrez J Altamirano AH Aguilar Carrasco JC Alvarado Acosta JL Aguilar Contreras A Alvarado Sansininea JJ Aguilar Faisal L Alvarez de la C C Aguilar Hernández A Álvarez MA Aguilar Laurents MI Alvizar-Medina AM Aguilar Mariscal H Amato Martínez D Aguilar Mariscal I Amezcua Gutiérrez MA Aguilera Suárez G Anaya-Ramos L Aguiñiga I Andreu-de-Riquer GA Aguirre Alvarado Ch Angeles Anguiano E Aguirre Bañuelos P Angeles E Aguirre Gómez A Antunes de Araujo A Aguirre Moreno AC Aparicio Fernández X Aguirre-Vidal Y Araujo Contreras JM Alarcón Aguilar FJ Arciniega Martínez IM Alba Leonel A Arellano A Alcántara Farfán V Arellano Mendoza M Alegría RPS Arellano Plancarte A Alejo Martínez A Arenas Téllez JM Allegre Alonso A Argüelles Hernández R Almaguer Vargas G Arias González I Almanza Orozco R Arias Montaño JA Arriaga Alba M 190 Atonal Flores F Bowery NG Ávalos Rodríguez A Briones Aranda A Ávalos Rodríguez A Briz V Avila Acevedo JG Buendía Pazaran JG Ávila Carrasco L Buendía Soto E Ávila G Burgueño Tapia E Avila ME Bye R Ávila Ortiz AG Calderón Guzmán D Ávila Rodríguez A Calpena AC Ávila Rodríguez H Calvillo M Ávila Velarde G Calzada Mendoza CC Avitia Dominguez C Camacho Carranza R Báez Saldaña A Camacho Luis A Baeza Ramírez I Campos Peña V Barajas López C Campos Rodríguez R Barragán Mejía G Campos Rodríguez UE Barrera Escorcia E Campos Sepúlveda AE Barrueco Noriega GS Cano Europa E Basurto Acevedo L Cano Martínez A Bautista Ávila M Cano Torres E Bautista Escalante CT Capellá D Bautista Pérez R Carbó R Becerril Montes A Cárdenas Jaramillo LM Bermúdez Ocaña DY Cárdenas N Blancas Mosqueda M Cárdenas Rodríguez N Blas Castillio J Carmona Aparicio L Blas Valdivia V Carrasco Portugal MC Blé Castillo JL Carrillo Ibarra S Bobadilla RA Carrillo Munguía N 191 Carvajal García-Pando A Contreras Chaires E Castañeda AD Coral Vázquez RM Castañeda Arroyo A Cordero D Castañeda Gonzáles C Cordero Martínez J Castañeda Hernández G Córdova Moreno R Castañeda S Córdova Pérez N Castillo Henkel C Corona Ortega T Castillo Henkel E Coronado Zarco IA Castillo Hernández MC Coronado Zarco R Castillo Kauil A Coronel I Castro Moreno P Correa Basurto J Castro Nelly Cortés López H Ceballos Reyes GM Cortés Mercado V Cervantes Espinoza JG Covarrubias A Cervantes M Cruz Laguna EY Chamorro Cevallos G Cruz Valderrama JE Changin Guerra A Cuevas Duran RE Chávez Alderete J Cuéllar Mendoza ME Chávez Pacheco JL Custodio V Chávez Piña AE Da Silva Solon LG Chiu Zárate R Déciga Campos M Chuc Meza E De la Cruz Marin A Ciprés Flores FJ De la Fuente Juárez G Cisneros Franco JM De la O De la O E Cisneros Mejorado AJ De los Santos S Clares B Del Bosque de la Berrera F Coballase Urrutia E Del Muro Casas FE Coelho Guerra GB Delgadillo Gutiérrez HJ Colin Martínez O Delgado A 192 Del Arenal Mena IP Fallas JM Demare P Farias Rodríguez M De Villa D Fenton Navarro B Díaz D Fenton Navarro B Díaz Reval MI Fernández F Díaz Ruíz A Fernández Guasti A Diaz Zagoya JC Fernández Herrera MA Dibildox Alvarado E Fernández Saavedra G Domínguez Campos A Fernández Vallin E Domínguez Marrufo LE Fetter Pruneda I Domínguez Quiñones PJ Fiesco Roa MO Domínguez Ramírez A Figueroa Hernández JL Doubova SV Figueroa Espitia JL Equiarte Solomón F Flo A Escalante Acosta B Flores Chávez P Escobar Ramírez JL Flores Guerrero JL Escobar Sánchez ML Flores Hernández J Escobedo Hinojosa WI Flores M J Escobedo Moratilla A Flores Murrieta FJ Escutia Calzada D Flores P Escutia CD Flores Pérez C Escutia Gutiérrez Raymundo Flores Pérez J Espinosa Aguirre J Flores Sáez JL Espinosa B Flores Soto E Espinosa García C Flores Villavicencio LL Espinosa Meléndez MT Flores Zepeda M Estebán Méndez M Fragoso Morales L Esteves M Franco A Fajardo Peregrina S Franco Colin M 193 Franco M García Saucedo B Franco Murillo Yanira García-Llamas E Fregoso Padilla M García-Montalvo EA Frías González S García Ramírez M Frias Soria C García Roca P Frias Zepeda E García Valencia G Fuentes Noriega I García Zabadúa JC Galaviz Hernández C Garduño ML Galicia Gutiérrez A Gasca Ramírez MV Galindo BE Gelista Herrera N Gallardo Casas CA Gerónimo Olvera C Gallardo Ortiz IA Gijón Granados E Gallegos Saucedo MJ Godínez Hernández D Galván Morales D Gómez Acevedo C Gálvez Gastelum FJ Gómez Cansino R Gámez Méndez A Gómez Galicia DL García Arenas G Gómez Montalvo A García Bores AM Gómez Olivares JL García Cruz ME Gómez Sánchez M García Chávez E Gómez Verján JC García de la Rosa LA González Cabañas J García Delgado AJ González Esquivel D García Iglesias BB González García X García Macedo JA González Gutiérrez AM García Martínez K González Hernández A González López EH García ML García Mondragón MJ García Ruiz M García Sánchez JR González R González Ríos J González Trujano ME González Zamora J 194 Goytia Acevedo R Hernández M Granados O Hernández Martínez M Granados Soto V Hernández Melesio MA Guadrón Llanos AM Hernández Pando R Guarneros Bañuelos E Hernández Ramírez H Guemez Ortiz KC Hernández Rebollar M Guerrero Zepeda MA Hernández Rodríguez M Guevara J Hernández Tellez B Guevara-Balcázar G Hernández Urbiola MI Guillé PG Hernández Valencia I Gutiérrez Coronado O Hernández Vázquez JMV Gutiérrez Hernández R Herrera De la Torre JD Gutiérrez Ospina G Herrera Gutiérrez H Guzmán Álvarez R Herrera Henríquez MA Guzmán Gutiérrez SL Herrera Pérez J Guzmán Hernández E Herrera Solis S Guzmán P Herrera Huerta EV Heras Romero Y Hong E Hernández AM Huacuja Ruíz L Hernández Aldana F Huerta Gertrudis B Hernández Alva A Huerta Herrera O Hernández Alvarado J Huerta Olvera SG Hernández Álvarez LA Huerto Cortés J Hernández Cabrera J Ibarra Barajas M Herrera De la Fuente RI Ibarra Cázeres AE Hernández García A Ibarra Guerrero I Hernández García E Islas Carbajal MC Hernández Luis F Izazola Conde C Hernández LLF Jaimez Melgoza R 195 Jardón Delgado A León I Jasso L León Palacios A Jiménez Bravo MA Lemini C Jiménez Capdeville ME Leopoldo M Jiménez Estrada I Letechipia Vallejo G Jiménez Orozco FA Licona Flores EA Jiménez Pérez N Limón D Jiménez Salgado T Linares E Jiménez Santos A Loera CV Jiménez Trejo F Londaíz Gómez R Jiménez Zamarripa CA López Aviña B Juárez B López Aymes G Juarez López R López Cabrera M Juarez Muñoz BE López Cabrera Y Juárez Olguin H López Canales JS Juárez Rocha V López canales O Juárez Rojo IE López Dávila M Jung Cook H López G Kubova H López Galindo G Lacivita E López Guerrero JJ Lara Riegos JC López Guzmán OD Lares Asseff I López Islas I Lares López A López López G Lascari Jiménez EC López M Lázaro R López Martínez IE Leal Anguiano AI López Muñoz FJ Leal Gutiérrez MA López Múñoz H Leandro Álvarez RD López Rodríguez M Leguízamo V López Sánchez P 196 López-López JG Martínez Casas M Lorenzana Jiménez M Martínez Cervantes A Loza Manjarrez G Martínez Cruz ME Lozano Guzmán E Martínez Enriquez ME Luévanos Raymundo MS Martínez Galero E Luna Cruz NA Martínez García E Luna Hernández AL Martínez González JJ Luna Nophal A Martínez Hernández A Luviano Jardón A Martínez L Magos Guerrero GA Martínez MT Maldonado Espinoza A Martínez Maldonado JD Maldonado Jhon Martínez Ramos F Maldonado PD Martínez Rider R Mallandrich M Martínez Rodríguez G Mancilla Percino T Martínez Rodríguez JL Mancilla Urrea E Martínez Vargas A Mandoki JJ Martínez Vázquez M Mandujano Morales JA McNaught Flores D Manrique Maldonado G Meaney A Manzanarez Colin MC Meaney E Marañón Ruíz VF Medeiros Domingo M Maravilla A Medina Campos ON Mares P Medina Enríquez MM Marichal Cancino BA Medina Jiménez M Márquez Delgado LE Medina Sifuentes AM Máquez Flores YK Medrano Morales J Márquez Orozco A Mejía Sánchez A Márquez Orozco MC Mejía Zepeda R Martínez Aguilar L Meléndez Camargo ME 197 Meléndez ME Montejano Rodríguez JR Méndez Córdoba E Montes de Oca Mejorada M Mendez Garrido A Montes de Oca Zavala V Mendez Tenório A Montes del Carmen P Mendiola Almaraz L Montes S Mendoza MA Montiel Ruiz RM Mendoza Meléndez MAG, Moralí G Mendoza Patiño N Moreno Bonett C Mendoza Rodríguez Y Mota Morales A Mera Jiménez E Muñoz Carrillo JL Mercado Camargo R Muñoz Fernández MA Mercado Hernández C Nateras Marín B Meza G Navarrete Castro A Meza Toledo SE Navarro Pineda D Meza R Nieto Alamilla G Meza Velázquez R Nieto Lima B Mino D Nogueda Torres B Miranda Beltrán ML Noriega Constantino MA Miranda Díaz AG Núñez Ortiz AR Miranda Osorio PH Ocampo López JO Miranda Rivera O Ocampo Mendoza K Miranda Torres A Ocharán Hernández ME Molina Guarneros JA Ögren SO Molina Ortiz D Olivares Corichi IM Mondragón de la Peña MC Olivos Cisneros L Monfil T Olvera Hernández EG Monroy Noyola A Olvera Hernámdez S Monsalvo I Ordaz Pichardo C Montaño Ramírez LM Ordoñez Librado JL 198 Orozco Cortés NV Patiño Camacho SI Orozco S Pedraza Chaverri J Orta García ST Peralta Cruz J Ortega Martínez N Peralta Rodríguez B Ortega Varela F Peralta Zimic M Ortiz Andrade RR Pérez Álvarez VM Ortiz Butrón R Pérez Barrón GA Ortiz L Pérez BE Ortiz Padilla AS Pérez Flores FJ Ortiz Plata Pérez Guillé BF Ortiz Segura MC Pérez Gutiérrez S Ortiz Vilchis MP Pérez Hernández IH Osorio Cruz Y Pérez López G Osorio H Pérez Meza JA Osorio Rico L Pérez Rosas NC Osorno Rivero O Pérez Severiano F Ossio R Pérez Torrero E Osuna Martínez U Pérez Severiano F Padilla Cortés P Pérez Urizar J Padilla Martínez I Pérez Vizcaíno F Padilla Pérez J Petricevich López VL Palacios Escalona S Pierdant Rioja FJ Palacios Espinosa JF Pineda-Olvera B Palencia Hernández G Pinto BM Palomares Alonso F Pinzón Estrada E, Palomino González G Polanco Ponce AC Palomino Torres N Pozos Guillén A Parra Gámez L Prado Alcalá RA Pastor O Quevedo Corona L 199 Quiliano Meza M Rico Urbina VH Quiñonez Palacio G Rincón Sánchez AR Quirarte GL Ríos Amelia Ramírez A Ríos Badillo V Ramirez Contreras E Ríos Castañeda C Ramírez Cruz AM Rivera Espinosa L Ramírez Flores E Rivero JJ Ramírez González MD Robles Piedras AL Ramírez J Roa Coria JE Ramírez Mendiola B Rocha L Ramírez Solares R Rodales Herrera JM Ramón Frias T Rodríguez Barrón A Ramos Dominguez R Rodríguez Fragoso L Rangel Corona R Rodríguez Galicia R Rangel Suarez G Rodríguez González JG Regla I Rodríguez JE Rembao-Bojórquez D Rodríguez Páez L Reséndiz Albor AA Rodríguez Romo S Reyes Antúnez E Rodríguez Sánchez R Reyes Chilpa R Rodríguez Vázquez T Reyes Esparza J Rojas C Reyes Estrada CA Rojas P Reyes García J Rojas Tomé S Reyes H Rojas Zaldívar E Reyes lagunes LI Román Ramos R Reyes López A Romano Moreno S Reyes Loyola PK Romero I Reyes Pérez M Romero R A Reza Garduño Treviño H Romero Rojas A 200 Rosales Hernández MC Sánchez Sánchez L Rosales Muñoz R Sandoval Bernal G Rosales Torres AM Sandoval Ramírez E Rosas Vargas H Sandoval Ramírez J Rubio García R Santamaría Juárez C Rubio Gayosso Santamaría del Angel D Rubio Osornio M Santana Carrillo J Rufino González Y Santana J Ruiz Azuara L Santiago E Ruiz de Chávez Mejía JÁ Santiago Mejía J Ruiz Salinas II Santoyo Pérez ME Ruiz Sánchez E Saracho Alarcón A Ruiz Vega H Saucedo Mendiola ML Sabanero López M Sebastián Barajas G Salas C Segura Cobos D Salas Pacheco JM Serrano García N Salazar Montes A Servín Santos JE Saldaña Balmori Y Sierra Vargas MP Saldívar González JA Sifuentes Franco S Salgado Chávez MA Silva Barrón CI Salinas Arreortua N Sommer B Saltzman S Soria Fragoso C Sánchez Alemán M Soriano Rosales RE Sánchez Cervantes I Soriano Ursúa MA Sánchez D Sosa Macías M Sánchez González JD Soto PCA Sánchez Maldonado C Soto Peña G Sánchez Martínez C Soto Vázquez R Sánchez Mendoza A Suárez Guerrero I 201 Suárez Méndez S Urbina Alvarez D Susunaga Notario AC Uribe Hernández A Tapia Aguilar R Urquieta Velázquez A Tapia Hernández A Urquiza Marín H Tavizón García JP Vacio Adame MP Téllez Valencia A Valadez Omaña MT Tena Betancourt E Valencia Hernández I Tenorio Guajardo G Valenzuela Vargas MT Terrón JÁ Valenzuela Limón OL Terrones Gurrola R Valverde Aguilar G Tiburcio R Vargas Becerra MH Tinoco Samos AE Vargas Fernández E Toledo A Vargas Medellín J Toledo López A Vargas Morales JM Tolentino López LE Vargas Olivos A Torner Aguilar L Vargas Robles H Torres N Vargas-Castillo AE Torres Pineda DB Vargas González A Torres Roque I Vázquez Cruz B Torres Ruíz NM Vázquez Martínez AM Totxo Guerrero SD Vázquez ML Tovilla Zárate CA Vázquez AO Trejo Muñoz CR Vázquez VH Tristán López L Vega Avila E Tristán-Agundis MF Vega Diaz F Tristan-López Luis Vega Rasgado L Trujillo Ferrara JG Velasco Lezama R Trujillo Jiménez F Velasco Lomas I Tufiño C Velázquez SMA 202 Velázquez Hernández ME Zenteno Galindo E Velázquez Ortiz IV Zepeda Rodríguez A Vélez Reséndiz JM Zugazagoitia Herrnaz R Vences Mejía A Ventura Martínez R Vergara Aragón P Vergara Onofre M Vértiz Harnández A Vértiz Hernández AA Vilchis M R Villa M Villafaña S Villalobos Gutiérrez PT Villalobos Molina R Villalón CM Villareal F Villeda Hernández J Villegas Álvarez F Villegas Bedolla JC Weiss.Steider B Wong Ramírez C Yahuaca Mendoza P Zamora de la Cruz D Zamora Gutiérrez D Zarco de Coronado I Zárate Treviño A Zarraga Galindo N Zavala Sánchez MA Zavala Tecuapletla C