Program - Semmelweis Egyetem

Transcription

2012. április 12-13.
PHD TUDOMÁNYOS NAPOK
2012
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2012. április 12-13.
Semmelweis Egyetem
Nagyvárad Téri Elméleti Tömb
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PhD. Tudományos Napok 2012
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2012. április 12-13.
ELŐSZÓ
Az évente megrendezett PhD Tudományos Napok a Semmelweis Egyetem nyolc Doktori Iskolájában
tanulmányokat folytató hallgatók és doktorjelöltek kiemelkedő tudományos fórumává vált. Vonzó jelentőségét az
idei évben is a program iránti érdeklődés, az előadások és poszter-bemutatók nagy száma jelzi. A rendezvényen
résztvevők az idei évben is a tudományos munka munltidiszciplináris seregszemléjének részesei lehetnek, hiszen
az Egyetem különböző tudományos műhelyeiben tevékenykedő PhD hallgatók és doktorjelöltek beszámolóin
keresztül a tudományterületek és tudományágak sokasága jelenik meg. A Semmelweis Egyetem Doktori
Iskoláinak hallgatóin kívül az előadók sorában az idei évben is örömmel üdvözöljük több hazai és külföldi
egyetem PhD hallgatóit.
A 2012. évi PhD Tudományos Napokon a PhD hallgatók és doktorjelelöltek tudományos előadásain és poszterbemutatóin kívül a 2011. évi Hugonnai Vilma Díj kitüntetettjeinek előadásait hallhatjuk. Dr. Zelkó Romána
egyetemi tanár és Dr. Müller Veronika egyetemi docens munkássága, tudományos és oktatói elkötelezettsége
irányt mutat és példaképül szolgál a tudományos életpályájukat éppen megkezdő fiatalok számára. A rendezvény
programjának további részeként a Doktori Iskolák PhD hallgatói 9 előadás és 7 poszter szekcióban számolnak be
tudományos munkájuk eredményeiről.
Őszintén remélem, hogy 2012. évi PhD Tudományos Napok programja hasznos tapasztalatokkal szolgál és
emlékezetes élményt jelent minden kedves résztvevőnek és érdeklődőnek.
Budapest, 2012. április 12.
Dr. Rácz Károly
egyetemi tanár
a Doktori Tanács elnöke
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2012. április 12-13.
TUDOMÁNYOS PROGRAM
2012. április 12. csütörtök
08.30 - 08.50
08.50 - 09.20
09.20 - 9.50
09.50 – 10.20
10.20 - 11.50
11:50 – 13.00
11.30 - 13.00
13.00 - 14.00
14.00 - 16.40
14.00 – 15.00
15.10 - 15.40
15.40 – 17:00
16.40 - 18.50
Megnyitó: Dr. Tulassay Tivadar egyetemi tanár, a Semmelweis Egyetem
rektora
Dr. Rácz Károly egyetemi tanár, a Semmelweis Egyetem Doktori
Tanácsának elnöke
2011. évi ”Hugonnai Vilma Díjas” előadó: Dr. Zelkó Romána egyetemi
tanár
A pozitron annihilációs élettartam spektroszkópia gyógyszerészeti
alkalmazásának lehetőségei
2011. évi ”Hugonnai Vilma Díjas” előadó: Dr. Müller Veronika
egyetemi docens
Celluláris stressz pulmonológiai kórállapotokban
Kávészünet
Előadások: E-I/1 - E-I/9
Előadások: E-II/1 – E-II/7
Poszterek: P-I/1 - P-I/7
Ebédszünet
Előadások: E-III/1 - E-III/16
Poszterek: P-II/1 – P-II/5
Kávészünet
Poszterek: P-III/1- P-III/7
Előadások: E-IV/1 – E-IV/13
2012. április 13. péntek
08.00 – 09.10
Előadások: E-V/1 – E-V/7
09.10 – 11.20
Előadások: E-VI/1 – E-VI/13
09.30 - 10.30
Poszterek: P-IV/1 – P-IV/6
10.30 – 11.00
Kávészünet
11.20 – 13.00
Előadások: E-VII/1 – E-VII/10
11.30 – 13.00
Poszterek: P-V/1 – P-V/10
13.00 – 14.00
Ebédszünet
14.00 – 15.50
Előadások: E-VIII/1 – E-VIII/11
14.00 – 15.00
Poszterek: P-VI/1 – P-VI/6
15.30 – 16.00
Kávészünet
15.50 – 17.40
Előadások: E-IX/1 – E-IX/11
16.00 – 17.00
Poszterek: P-VII/1 – P-VII/6
18.00 - 18.30
Zárszó, díjkiosztó
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2012. április 12-13.
TABLE OF CONTENTS
E/I ORAL PRESENTATIONS
Chairman: Prof. Dr. Zoltán Benyó
E/I-1
TRANSIENT OUTWARD POTASSIUM CURRENT IN DOG ATRIAL
PREPARATIONS
Claudia Corici, Zsófia Kohajda, Attila Kristóf, Tamás Szél, Zoltán Husti, István Baczkó,
András Varró, László Virág, Norbert Jost
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E/I-2
LATEST RESULTS OF THE RESPIRATORY ASPECTS OF THE
INTERNATIONAL TWIN STUDY
David Laszlo Tarnoki, Adam Domonkos Tarnoki, Emanuela Medda, Levente Littvay, Zsofia
Lazar, Rodolfo Cotichini, Corrado Fagnani, Maria Antonietta Stazi, Lorenza Nisticó,
Pierleone Lucatelli, Emanuele Boatta, Chiara Zini, Fabrizio Fanelli, Claudio Baracchini,
Giorgio Meneghetti, Akos Koller, Janos Osztovits, Gyorgy Jermendy, István Préda, Róbert
Gábor Kiss, Kinga Karlinger, Agnes Lannert, Giuseppe Schillaci, Andrea Agnes Molnar,
Zsolt Garami, Viktor Berczi, Ildiko Horvath
24
E/I-3
SOPHISTICATED ARRHYTHMIA DETECTION WITH 256-SLICE CT
ALLOWS DIAGNOSTIC CORONARY ARTERY IMAGING IN PATIENTS WITH
ATRIAL FIBRILLATION
CORONARY CT ANGIOGRAPHY WITH 256-SLICE SCANNER IN PATIENTS
WITH ATRIAL FIBRILLATION
Mihály Károlyi, Andrea Bartykowszki, Erik Formanek, Mohammed Muhemin, Csaba
Csobay-Novák, Nándor Pintér, Kálmán Hüttl, György Balázs, Béla Merkely, Pál MaurovichHorvat
26
E/I-4
THE ROLE OF MICRORNAS IN RENAL ISCHEMIA-REPERFUSION INJURY
Tamás Kaucsár, Csaba Révész, Mária Godó, Zsuzsanna Rácz, Róbert Tarszabó, Péter Hamar
27
E/I-5
ISOLATION AND CULTURE OF RAT BONE MARROW MESENCHYMAL
STEM CELLS
Kinga Lakatos, Éva Szigetfű, Zsuzsanna Lendvai, Zoltán Nagy, Béla Merkely, Judit Skopál
28
E/I-6
CARDIOPULMONARY BYPASS IMPAIRS BRAIN OXYGENATION AS
DEMONSTRATED BY NEAR-INFRARED SPECTROSCOPY
Peter Mukli
29
E/I-7
PREDICTORS OF CRT-INDUCED LEFT VENTRICULAR REVERSE
REMODELING
Vivien Klaudia Nagy, Valentina Kutyifa, Astrid Apor, Csilla Liptai, Eszter Édes, Gábor
Széplaki, Béla Merkely
30
E/I-8
LATEST RESULTS OF THE CARDIOVASCULAR AND ANTHROPOMETRIC
ASPECTS OF THE INTERNATIONAL TWIN STUDY
Adam Domonkos Tarnoki, David Laszlo Tarnoki, Emanuela Medda, Maria Antonietta Stazi,
Rodolfo Cotichini, Corrado Fagnani, Lorenza Nisticó, Pierleone Lucatelli, Emanuele Boatta,
Chiara Zini, Fabrizio Fanelli, Claudio Baracchini, Giorgio Meneghetti, Janos Osztovits,
Gyorgy Jermendy, István Préda, Róbert Gábor Kiss, Levente Littvay, Julia Metneki, Tamas
Horvath, Kinga Karlinger, Agnes Lannert, Andrea Agnes Molnar, Zsolt Garami, Pal Bata,
Gyorgy Baffy, Giuseppe Schillaci, Viktor Berczi
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7
E/I-9
TWELVE-HOLES GOLD ELECTRODE ABLATION CATHETER PROVED TO
BE EFFECTIVE AND SAFE ALSO AT REDUCED IRRIGATION FLOW RATE
Eszter Mária Végh, Endre Zima, Tamás Szili-Török, Gábor Széplaki, Márta Hubay, Luc
Jordaens, László Gellér, Béla Merkely
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E/II ORAL PRESENTATIONS
Chairman: Dr. Gábor Békési
E/II-1
REGULATION OF GENE TRANSCRIPTION BY GLUCOCORTICOID
RECEPTOR (GR) ΒETA-ISOFORM
Bence T. Ács, István Likó, Karolina Feldman, Péter M Szabó, Henrietta Butz, Károly Rácz,
Attila Patócs
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E/II-2
THE MYCOBACTERIAL DUTPASE: BIOCHEMISTRY, PHYSIOLOGY AND
MOLECULAR INTERVENTION
Rita Hirmondo, Ildiko Pecsi, Anna Lopata, Amanda C. Brown, Tanya Parish, Beata G.
Vertessy, Judit Toth
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E/II-3
ABSORPTION AND TENSILE STRENGTH OF CELL-COATED SUTURES
Denes Horvathy, Gabriella Vacz
39
E/II-4
DETECTION OF EARLY GLAUCOMATOUS PROGRESSION WITH THE
RTVUE OPTICAL COHERENCE TOMOGRAPH AND SCANNING LASER
POLARIMETRY
Farzaneh Naghizadeh, Anita Garas, Péter Vargha, Gábor Holló
40
E/II-5
COLORECTAL CARCINOGENESIS FROM AN EPIGENETIC POINT OF
VIEW: WHAT CAN DNA METHYLATION ADD TO THE BETTER
MOLECULAR UNDERSTANDING OF ADENOMA-DYSPLASIA-CARCINOMA
SEQUENCE?
Árpád V. Patai, Orsolya Galamb, Gábor Valcz, Alexanda Kalmár, Árpád Patai, Bálint
Péterfia, B. Wichmann, Katalin Leiszter, Kinga Tóth, Andrea Schöller, István Fűri, Barbara
Kinga Barták, Zsófia Brigitta Nagy, Sándor Spisák, Ferenc Sipos, Tibor Krenács, Béla
Molnár, Zsolt Tulassay
41
E/II-6
INVESTIGATION OF TRANSPORTER INTERACTIONS OF
ANTIMALARIALS IN VITRO
Péter Szerémy, Ildikó Makai, Márton Jani, Marton Lívia, Szilvia Gedey, Katalin Jakab, János
Márki-Zay, Péter Krajcsi
43
E/II-7
ANALYZING THE RELIABILITY OF THE SPINAL INSTABILITY
NEOPLASTIC SCORE
Zsolt Szövérfi, Árpád Bozsodi
44
E/III ORAL PRESENTATIONS
Chairman: Prof. Dr. Károly Cseh
E/III-1
PH REGULATION DURING AMELOGENESIS – FUNCTIONAL EVIDENCE
OF BICARBONATE TRANSPORT IN HAT-7 AMELOBLAST CELLS
Erzsébet Bori
47
E/III-2
AMBULATORY ARTERIAL STIFFNESS INDEX IN CHILDREN AFTER
KIDNEY TRANSPLANTATION – CROSS SECTIONAL STUDY
Arianna Dégi, Andrea Kerti, Attila J. Szabó, Péter Sallay, Éva Kis, Orsolya Cseprekál, George
S. Reusz
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2012. április 12-13.
E/III-3
CHANGES IN PHOTOPIGMENT EXPRESSION AND PHOTORECEPTOR
MORPHOLOGY IN EARLY DIABETES
Anna Énzsöly, Arnold Szabó, Klaudia Szabó, Ákos Lukáts, János Németh
49
E/III-4
CLINICOPATHOLOGICAL FEATURES OF LUNG CANCER WITH BRAIN
METASTASES
Katalin Fábián
50
E/III-5
POLYMORPHISM OF THE HSD11B1 GENE PROMOTER INFLUENCES
BONE MINERAL DENSITY
Karolina Feldman, Ágnes Szappanos, Zsófia Kövesdi, Miklós Tóth, István Likó, Péter
Lakatos, Károly Rácz, Attila Patócs
51
E/III-6
POSTCONDITIONING AS A PREVENTION METHOD AFTER LOWER LIMB
ISCHEMIA-REPERFUSION INJURY: REDUCING DAMAGES OF THE LUNG
Dávid Garbaisz, Zsolt Turóczi, Olivér Rosero, Gábor Lotz, Zoltán Rakonczay, László
Harsányi, Attila Szijártó
52
E/III-7
ANTI-INFLAMMATORY EFFECTS OF MOUSE MESENCHYMAL STEM
CELLS ON MICROGLIA
Beáta Hegyi
53
E/III-8
SIGMA-1 RECEPTOR AGONIST TREATMENT IS PROTECTIVE AGAINST
RENAL ISCHEMIA/REPERFUSION INJURY
Ádám Hosszú, Nóra Fanni Bánki, Zsuzsa Antal, Sándor Kőszegi, László Wagner, Ágnes
Prókai, Ádám Vannay, Veronika Müller, Attila Szabó, Andrea Fekete
54
E/III-9
NPHS2 P.V290M MUTATION IN LATE-ONSET STEROID-RESISTANT
NEPHROTIC SYNDROME
Andrea Kerti, Rózsa Csohány, Attila Szabó, Péter Sallay, György Reusz, Kálmán Tory
55
E/III-10
THE ROLE OF THE SIGMA-1 RECEPTOR IN DIABETIC NEPHROPATHY
Sándor Kőszegi, Bánki Nóra Fanni, Ádám Hosszú, László Wagner, Ágnes Prókai, Ádám
Vannay, Tivadar Tulassay, Andrea Fekete
56
E/III-11
ACTIVATION OF SMAD 2 AND 3 IN THE INTESTINAL MUCOSA OF
PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND IN
HT-29 CELL LINES
Kriszta Molnar, Ádám Vannay, Leonóra Balicza-Himer, Apor Veres-Székely, Dolóresz
Szabó, Nóra Fanni Bánki, András Arató, Gábor Veres
57
E/III-12
THE EFFECTS OF POSTCONDITIONING IN A LONG-TERM PERIOD RAT
LIVER ISCHEMIC-REPERFUSION EXPERIMENTAL MODEL
Rosero Olivér, Ónody Péter, Garbaisz Dávid, Tamás Judith, Kocsis Ibolya, Lotz Gábor,
Harsányi László, Szijártó Attila
58
E/III-13
POSITIONAL IDENTITY OF MURINE MESENCHYMAL STEM CELLS
RESIDENT IN DIFFERENT ORGANS IS DETERMINED IN THE
POSTSEGMENTATION MESODERM
Bernadett Sági
59
E/III-14
BIOMARKERS OF BONE FORMATION AND GUT PERMEABILITY IN
LONG-TERM INFLIXIMAB THERAPY IN PEDIATRIC PATIENTS WITH
CROHN'S DISEASE
Doloresz Szabó, Katalin Köles, Antal Dezsőfi, András Arató, Gábor Veres
60
9
E/III-15
9-CIS-RETINOIC ACID-INDUCED GENE EXPRESSION ALTERATIONS IN
AN ADRENOCORTICAL CELL LINE
Diana Rita Szabó, Peter M. Szabó, Adrienn Zsippai, Katalin Éder, Attila Patócs, András
Falus, Károly Rácz, Peter Igaz
61
E/III-16
DIFFERENT ADJUVANT ANTIOXIDANT TREATMENTS IN FATTY LIVER
Viktor Hegedüs, Dénes Kleiner, Kálmán Ditrói, József Prokisch, Hedvig Fébel, Éva Sárdi,
Gábor Lotz, Attila Szijártó, Anna Blázovics
62
E/IV ORAL PRESENTATIONS
Chairman: Dr. Péter Hamar
E/IV-1
THE FIRST CENTRAL-EUROPEAN CARDIOVASCULAR PREVENTION
STUDY - BUDAKALASZ HEALTH EXAMINATION SURVEY
Zsolt Bagyura, Zsolt Szelid, Pál Soós, Loretta Kiss, Béla Merkely
65
E/IV-2
EFFECTS OF THE BENZODIAZEPINE DERIVATIVE, 5-BDBD ON THE P2X4
PURINERGIC RECEPTOR CHANNEL
Bernadett Balázs, Tamás Dankó, Fanni Noémi Rocskó, Ákos Zsembery
66
E/IV-3
H2S PRECONDITIONING OF THERAPEUTICALLY USED STEM CELLS
INCREASES THEIR SURVIVAL AND EFFICACY IN AN IN VITRO MODEL
OF CELL-BASED THERAPY IN MYOCARDIAL INFARCT
Zsolt Benkő, Eleni Dongó, Ágnes Csizmazia, Mónika Szepes, Zsófia Janicsek, Levente Kiss
67
E/IV-4
BILAYER EDGES CATALYZE LIPOSOME BINDING, MOVEMENT AND
RUPTURE ON SOLID SURFACES
Tamás Bozó
68
E/IV-5
CORONARY INTERVENTION LEADS TO COMPLEMENT ACTIVATION
THROUGH THE ALTERNATIVE PATHWAY
Zsófia Horváth, Dorottya Csuka, Katarina Vargova, Andrea Kovács, Andrea Ágnes Molnár,
Leé Sarolta, Lilian Varga, Róbert Gábor Kiss, István Préda, George Füst
69
E/IV-6
NANOMECHANICS OF DESMIN FILAMENTS EXPLORED WITH OPTICAL
TWEEZERS
Balázs Kiss, Pasquale Bianco
70
E/IV-7
REVERSIBLE LOW-FORCE-DRIVEN STRUCTURAL TRANSITIONS IN
SKELETAL MUSCLE TITIN REVEALED BY FORCE-CLAMP OPTICAL
TWEEZERS
Zsolt Mártonfalvi, Pasquale Bianco, Miklós Kellermayer
71
E/IV-8
DETAILED HEMODYNAMIC CHARACTERIZATION OF ATHLETE’S
HEART USING LEFT VENTRICULAR PRESSURE-VOLUME ANALYSIS IN A
RAT MODEL
Attila Oláh, Árpád Lux, Ede Birtalan, László Hidi, Balázs Németh, Béla Merkely, Tamás
Radovits
72
E/IV-9
MEASURMENT OF PLATELET ADHESION USING IMPEDANCE BASED
TECHNIQUE
Lívia Polgár
73
E/IV-10
NANOMECHANICAL MANIPULATION OF MASON-PFIZER MONKEY
RETROVIRAL RNA FRAGMENT WITH OPTICAL TWEEZERS
Melinda Simon, Zsolt Mártonfalvi, Pasquale Bianco, Beáta Vértessy, Miklós Kellermayer
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2012. április 12-13.
E/IV-11
THE EFFECT OF THE OBSTRUCTIVE SLEEP APNEA ON THE NIGHTTIME GLUCOSE VARIABILITY IN PATIENTS WITH METABOLIC
SYNDROME
Orsolya A. Veber, Andrea Dunai, Rezso Zoller, Zsofia Lendvai, Anett V. Lindner, Istvan
Mucsi
75
E/IV-12
THE ATHLETE’S HEART
Zsuzsanna Major, Zsuzsanna Kneffel, Tímea Kováts, Eszter Csajági
76
E/IV-13
DIFFERENT MITOCHONDRIAL BIOGENESIS TO EXERCISE TRAINING IN
LOW AND HIGH EXERCISE RESPONDER RATS
Orsolya Marton, Erika Koltai, Ferenc Torma, Steven Britton, Lauren Koch, Zsolt Radák
77
E/V ORAL PRESENTATIONS
Chairman: Dr. Árpád Dobolyi
E/V-1
PROTEIN-PROTEIN INTERACTIONS REGULATE THYROID HORMONE
ACTIVATION
Péter Egri, Balázs Gereben
81
E/V-2
FASTING-INDUCED ALTERATIONS IN THE Α-MSH- AND AGRPIMMUNOREACTIVE INNERVATION OF TRH-SYNTHESIZING NEURONS
IN THE HYPOTHALAMIC PVN
Andrea Kádár, Edith Sanchez, Balázs Gereben, Ronald M. Lechan, Csaba Fekete
82
E/V-3
A REDUCTION IN THE ACTIVITY OF ALPHA-KETOGLUTARATE
DEHYDROGENASE COMPLEX DECREASES MATRIX SUBSTRATE-LEVEL
PHOSPHORYLATION AND PROMPTS RESPIRATION-IMPAIRED
MITOCHONDRIA TOWARDS EXTRAMITOCHONDRIAL ATP
CONSUMPTION
Gergely Kiss, Csaba Konrád, Anatoly A. Starkov, Hibiki Kawamata, Giovanni Manfredi,
Steven F. Zhang, Gary E. Gibson, M. Flint Beal, Vera Adam-Vizi, Christos Chinopoulos
83
E/V-4
MONOCARBOXYLATE-TRANSPORTER-8 AND TYPE 3 DEIODINASE IN
AXON TERMINALS OF THE MEDIAN EMINENCE ALLOW SYSTEMSPECIFIC REGULATION OF T3-ACTION IN HYPOTHALAMIC
HYPOPHYSIOTROPIC NEUROSECRETORY NEURONS
Petra Mohácsik, Imre Kalló, Barbara Vida, Anikó Zeöld, Zsuzsanna Bardóczy, Erzsébet
Farkas, Andrea Kádár, Antonio C. Bianco, Zsolt Liposits, Csaba Fekete, B. Gereben
84
E/V-5
AGING COINCIDES WITH MORPHOLOGICAL ALTERATIONS OF
KISSPEPTIN AND NEUROKININ B NEURONS IN THE INFUNDIBULAR
NUCLEUS OF THE HUMAN MALE
Csilla S. Molnár, Barbara Vida, Máté Sipos, Imre Kalló, Philippe Ciofi, Beáta Borsay, Stephen
R. Bloom, Mohammad A. Ghatei, Waljit S. Dhillo, Zsolt Liposits, Erik Hrabovszky
85
E/V-6
ALTERNATIVE SPLICING OF EGFR ECD IN HUMAN MELANOMA
Eleonóra Imrédi
86
E/V-7
MIRNA EXPRESSION PROFILE OF ADENOID CYSTIC CARCINOMA OF
SALIVARY GLANDS AND THE BREAST: PRELIMINARY RESULTS
Orsolya Kiss, Anna-Mária Tőkés, Sándor Spisák, Eszter Gábori, Anikó Bata, Subramanian
Kumar, Borbála Székely, Attila Marcell Szász, Janina Kulka
87
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E/VI ORAL PRESENTATIONS
Chairmen: Prof. Dr. István Bitter, Dr. János Réthelyi, Dr. Róbert Bódizs
E/VI-1
BEHAVIOURAL-EPIDEMIOLOGICAL ANALYSIS OF ADOLESCENTS’
SMOKING IN A POPULATION OF A SMALL TOWN BETWEEN 2008 AND 2010
Mate A. Balazs, Bettina F. Piko
91
E/VI-2
SUBTHRESHOLD PSYCHIATRIC CONDITIONS IN CHILD PSYCHIATRY: A
LONGITUDINAL STUDY
Eszter Anna Bertha
92
E/VI-3
RELATIONSHIP BETWEEN PSYCHOLOGICAL RISK FACTORS AND
SOMATIC FACTORS IN ACUTE CORONARY SYNDROMES
Beatrix Rafael, Piroska Balog
93
E/VI-4
OBSTETRICAL AND GYNECOLOGICAL CONSEQUENCES OF EATING
DISORDERS
Szilvia Dukay-Szabó
94
E/VI-5
ADVERSE LIFE EVENTS AND SUICIDE RISK IN PEOPLE WITH
SCHIZOPHRENIA
Krisztina Kocsis-Bogár, Dóra Perczel-Forintos, Mónika Miklósi
95
E/VI-6
EFFECTS OF CURRENT ALCOHOL AND TOBACCO CONSUMPTION ON
PHYSICAL AGGRESSION AND ADHD SYMPTOMS AMONG HUNGARIAN
ADOLESCENTS
Balázs Matuszka, Erika Bácskai, József Gerevich
96
E/VI-7
THE EFFECT OF PERCEIVED PARENTAL EFFICACY ON PARENTS’
GENERAL DISTRESS AFTER THEIR CHILD’S SURGERY
Mónika Miklósi, Elvira Galambosi
97
E/VI-8
BEHAVIOURAL INHIBITION AND IMPULSIVITY IN ADULT ATTENTION
DEFICIT HYPERACTIVITY DISORDER
Szilvia Papp, László Tombor, Brigitta Kakuszi, Lívia Balogh, Viktória Simon, Pál Czobor
98
E/VI-9
QUANTITATIVE EEG IN ADULT ATTENTION DEFICIT/
HYPERACTIVITY DISORDER (ADHD)
LÁSZLÓ TOMBOR, SZILVIA PAPP, BRIGITTA KAKUSZI, LÍVIA BALOGH,
VIKTÓRIA SIMON, PÁL CZOBOR
99
E/VI-10
SUICIDAL BEHAVIOR: PSYCHOLOGICAL AND ETHNICAL DIFFERENCES
IN THE SERIOUSNESS OF DELIBERATE SELF POISONING
Mónika Ditta Tóth, András Székely, Szilvia Ádám, Tamás Zonda, Mária Kopp
100
E/VI-11
ASSOCIATION BETWEEN LUNAR PHASE AND SLEEP CHARACTERISTICS
Csilla Zita Turányi, András Szentkirályi, Mária Czira, Andrea Dunai, Julianna Szőcs, Orsolya
Véber, Katalin Rónai, Andrea Kelemen, Rezső Zoller, Márta Novák, István Mucsi
101
E/VI-12
COMORBID FACTORS OF INDIVIDUALS WITH A TENDENCY TO
ORTHOREXIA NERVOSA
Márta Varga, Szilvia Dukay-Szabó, Ferenc Túry, Eric F. van Furth
102
E/VI-13
VARIANTS IN CATECHOL-O-METHYLTRANSFERASE GENE ARE
ASSOCIATED WITH IMPULSIVITY AND EXECUTIVE FUNCTION:
RELEVANCE FOR MAJOR DEPRESSION
Dorottya Pap, Ian M. Anderson, J.F. William Deakin, Gyorgy Bagdy, Gabriella Juhasz
103
12
2012. április 12-13.
E/VII ORAL PRESENTATIONS
Chairman: Prof. Dr. Gábor Bánhegyi
E/VII-1
MODULATION OF EXPERIMENTAL MODELS OF AUTOIMMUNITY BY
EXTRACELLULAR VESICLES
Borbála Aradi, Krisztina Pálóczi, Petra Misják, Bence György, Tamás G. Szabó, Ágnes Kittel,
Szilvia Bősze, Kata Horváthi, Krisztina Holló, Katalin Szabó-Taylor, Mária Pásztói, András
Falus, Edit I. Buzas
107
E/VII-2
INQUIRING ABOUT AVIAN THYMIC DENDRITIC CELLS
Ildikó Bódi
108
E/VII-3
ASSOCIATION AND MOLECULAR ANALYSIS OF THE WFS1 GENE
Zsuzsanna Elek
109
E/VII-4
IN VITRO AND CELLULAR STUDY OF EGFR – C-MET KINASE INHIBITORS
IN NSCLC CELL LINES
Pal Gyulavari, Balint Szokol, Ibolya Kurko, Gyorgyi Bokonyi, Gabor Borbely, Csaba SzantaiKis, Laszlo Orfi, Istvan Petak, Gyorgy Keri, Tibor Vantus
110
E/VII-5
ABSENCE OF CA2+-INDUCED MITOCHONDRIAL PERMEABILITY
TRANSITION BUT PRESENCE OF BONGKREKATE-SENSITIVE
NUCLEOTIDE EXCHANGE IN C. CRANGON AND P. SERRATUS
Csaba Konrad, Gergely Kiss, Beata Torocsik, Vera Adam-Vizi, Christos Chinopoulos
111
E/VII-6
IKZF1 AND ARID5B GENE POLYMORPHISMS INFLUENCE THE
SUSCEPTIBILITY TO CHILDHOOD ACUTE LYMPHOID LEUKEMIA
Orsolya Lautner-Csorba, Ágnes F. Semsei, András Gézsi, Nóra Kutszegi, András Falus,
Csaba Szalai
112
E/VII-7
INVESTIGATION OF THE MIRNA BINDING SITE POLYMORPHISMS OF
THE SNAP-25 GENE
Nóra Németh, Réka Kovács-Nagy, Zsolt Rónai, Mária Sasvári-Székely
113
E/VII-8
REGULATION OF CASKIN1 SCAFFOLD PROTEIN BY EPHB1 TYROSINE
KINASE
Szabolcs Pesti, Annamária Balázs, Beáta Szabó, László Buday
114
E/VII-9
EFFECT OF EGCG ON MICROSOMAL CORTISOL PRODUCTION
Péter Szelényi
115
E/VII-10
SWITCHING ON RNA SILENCING SUPPRESSOR ACTIVITY BY
REMODELING THE ARGONAUTE BINDING DOMAIN
Edit Szabó, Máté Manczinger, Anikó Göblös, Lajos Kemény, Lóránt Lakatos
116
E/VIII ORAL PRESENTATIONS
Chairperson: Prof. Dr. Éva Szökő
E/VIII-1
INDICATION OF BRAIN PENETRABLE COMPOUNDS IN PLANT
EXTRACTS BY PAMPA-BBB – LC-MS ASSAY
Árpád Könczöl, Ágnes Kéry, Judit Müller, Emília Földes, György T. Balogh
119
E/VIII-2
PHARMACOLOGICAL REGULATION OF TUMOR CELL ADHESION AND
MIGRATION BY CYTOTOXIC GNRH-III CONJUGATES AND R-DEPRENYL
DERIVATIVES TO PREVENT METASTASIS FORMATION
Eszter Lajkó, Lívia Polgár, Marilena Manea, Gábor Mező, Kálmán Magyar, László Kőhidai
120
13
E/VIII-3
IMPACT OF THE AQUATIC POLLUTANT HUMAN PHARMACEUTICALS
AND THEIR MIXTURES ON THE PROLIFERATION AND MIGRATORY
BEHAVIOR OF THE FRESHWATER CILIATE TETRAHYMENA
PYRIFORMIS
Júlia Láng, László Kőhidai
121
E/VIII-4
DETERMINATION AND STUDY ON DOSE LINEARITY OF THE
PHARMACOKINETICS OF M-CHLOROPHENYLBIGUANIDE USING A
NEWLY DEVELOPED HPLC UV AND EC METHOD
Rudolf Laufer, Péter Szegi, Viola Csomor, Kornélia Tekes
122
E/VIII-5
TRIPODAL ION-BINDING RECEPTORS: SYNTHESIS AND
CHARACTERIZATION
Gábor Neumajer, Attila Marosi, Szabolcs Béni, Béla Noszál
123
E/VIII-6
PHARMACOKINETICS OF K203, A BIS-PYRIDINIUM MONO-ALDOXIME
CHOLINESTERASE REACTIVATOR IN RATS AND BEAGLE DOGS
Zita Pöstényi, Péter Szegi, Balázs Tasnádi
124
E/VIII-7
OPTIMIZATION PROCESS AND HPLC BEHAVIOR OF SOME NOVEL BISPYRIDINIUM ALDOXIMES
Péter Szegi, Zita Pöstényi, Balázs Tasnádi, Rudolf Laufer, Kamil Kuča
125
E/VIII-8
CHARACTERIZATION OF OFLOXACIN-CYCLODEXTRIN COMPLEXATION
Gergő Tóth, Réka Mohácsi, Ákos Rácz, Aura Rusu, Péter Horváth, Szabolcs Béni,
Béla Noszál
126
E/VIII-9
SAMPLE PRE-FRACTIONATION METHOD FOR ANALYSIS OF
GLYCOPROTEINS FROM HUMAN PLASMA
Eszter Tóth, Oliver Ozohanics, Lilla Turiák
127
E/VIII-10
GLUCOSIDES OF MORPHINE CONGENERS: SYNTHESIS AND
CHARACTERIZATION
András Váradi, Dóra Lévai, Gergő Tóth, Péter Horváth, Sándor Hosztafi
128
E/VIII-11
CHARACTERIZATION THE EFFECTS OF A NOVEL PKD1 INHIBITOR IN
VEGF SIGNALING PATHWAY ON ENDOTHELIAL CELLS
Attila Varga, Csaba Szántai-Kis, Zoltán Horváth, Zoltán Greff, László Őrfi, György Kéri,
Tibor Vántus
129
E/IX ORAL PRESENTATIONS
Chairman: Prof. Dr. László Kopper
E/IX-1
CHANGES OF MIRNA EPRESSION PATTERN DURING THE HUMAN
MELANOMA PROGRESSION
Tamás Barbai, Erzsébet Rásó
133
E/IX-2
ANGIOGENESIS IS CHALLENGED IN EXPERIMENTAL BRAIN
METASTASES
Edina Bugyik, Vanessza Szabó, Katalin Dezső, Péter Nagy, Sándor Paku
134
E/IX-3
HEPATOCARCINOGENESIS IN MATRILIN-2 KNOCK OUT MICE
Alexandra Fullár, Kornélia Baghy, Ferenc Deák, Bálint Péterfia, Zsuzsa Schaff, József Dudás,
Ibolya Kiss, Ilona Kovalszky
135
14
2012. április 12-13.
E/IX-4
ONCOGENIC MUTATION DEPENDENT EFFECT OF PRENYLATION
INHIBITION IN MELANOMA CELLS
Tamás Garay, István Kenessey, Éva Juhász, Andrea Réti, Viktória László, Judit Dobos,
Violetta Piurkó, Walter Berger, József Tóvári, József Tímár, Balázs Hegedűs
136
E/IX-5
GENETIC AND EPIGENETIC EXAMINATION OF THE SMARCB1/INI1
GENE IN EPITHELIOID SARCOMA
Gergő Papp
137
E/IX-6
EXAMINATION OF TARGETED SNP VARIANTS IN SIX GENES WITH
POSSIBLE EFFECT ON ADULT CRANIAL SUTURE SYNOSTOSIS
Katalin Wolff, Zoltán Vas, Éva Hadadi
138
E/IX-7
ANTIVIRAL EFFECTS OF A FERMENTED WHEAT GERM EXTRACT
(AVEMAR), IN THE FELINE AIDS MODEL
Balázs Stercz
139
E/IX-8
mTORC1 AND C2 EXPRESSION IN HUMAN COLON CANCER
Tamás Sticz, Anna Sebestyén, Ágnes Márk, Melinda Hajdu, Tamás Micsik, Noémi Nagy,
László Kopper
140
E/IX-9
CONNECTIONAL HIERARCHY IN THE PRIMARY SOMATOSENSORY
CORTEX OF PRIMATES
Maria Ashaber, Emese Pálfi, Cory Palmer, Orsolya Kantor, Robert M. Friedman, Anna W.
Roe, Laszlo Négyessy
141
E/IX-10
LAMINAR ANALYSIS OF THE SLOW CORTICAL RHYTHM IN RAT
SOMATOSENSORY CORTEX UNDER KETAMINE/XYLAZINE ANESTHESIA
Richárd Fiáth, Bálint Péter Kerekes, György Karmos, István Ulbert
142
E/IX-11
CENTRAL AMYLIN IS A NOVEL NEUROPEPTIDE WITH POTENTIAL
MATERNAL FUNCTIONS IN RAT
Éva Rebeka Szabó, Melinda Cservenák, Árpád Dobolyi
143
P/I POSTER PRESENTATIONS
Chairman: Dr. Barna Vásárhelyi
P/I-1
EXAMINATION OF PHOTOSENSITIZER-CELLULAR MEMBRANE MODEL
WITH OPTICAL SPECTROSCOPY METHODS
Dániel Veres, Barnabás Bőcskei-Antal
147
P/I-2
RED BLOOD CELL DISTRIBUTION WIDTH PREDICTS UNFAVOURABLE
OUTCOME FOLLOWING CARDIAC RESYNCHRONIZATION THERAPY
Annamaria Kosztin, Gabor Szeplaki, Eszter Maria Vegh, Szabolcs Szilagyi, Istvan
Osztheimer, Levente Molnar, Endre Zima, Laszlo Geller, Zoltan Prohaszka, Bela Merkely
148
P/I-3
THE EFFECT OF OBESTATIN ON BEHAVIORAL RESPONSES INDUCED
BY MORPHINE WITHDRAWAL IN MICE
Nándor Lipták, Roberta Dochnal, Krisztina Csabafi, Júlia Szakács, Gyula Szabó
149
P/I-4
ELASTIC, CONTRACTILE AND ENDOTHELIAL PROPERTIES OF HUMAN
VEIN SEGMENTS STORED IN A COMPLEX TISSUE MEDIUM
Anna Monori-Kiss, Gábor Ferenc Molnár, Attila Nemes, Violetta Kékesi, Emil Monos,
György László Nádasy
150
15
P/I-5
COMPARISON OF EPITAXIALLY AND SOLUTION-GROWN AMYLOID ß25-35
FIBRILS
Ünige Murvai, Judit Somkuti, Katalin Soós, Botond Penke, László Smeller, Miklós S. Z.
Kellermayer
151
P/I-6
TEMPERATURE-PRESSURE STABILITY AND T-P PHASE DIAGRAM OF
PARVALBUMIN
Judit Somkuti, Merima Bublin, Heimo Breiteneder, László Smeller
152
P/I-7
RENAL FUNCTION IS ASSOCIATED WITH RED CELL DISTRIBUTION
WIDTH INDEPENDENT OF IRON DEFICIENCY AND NUTRITIONAL
STATUS IN KIDNEY TRANSPLANT RECIPIENTS
Ákos Ujszászi, Mária Eszter Czíra, Ádám Remport, Csaba Pál Kövesdy, Anna Rudas, Miklós
Zsolt Molnár, István Mucsi
153
P/II POSTER PRESENTATIONS
Chairman: Dr. Csaba Fekete
P/II-1
NMDA RECEPTORS IN GABAERGIC SYNAPSES DURING POSTNATAL
DEVELOPMENT
Csaba Cserép, Eszter Szabadits, András Szőnyi, Masahiko Watanabe, Tamás F. Freund,
Gábor Nyiri
157
P/II-2
POSTERIOR THALAMIC TIP39 NEURONS PROJECT TO THE MEDIAL
HYPOTHALAMUS AND REGULATE PROLACTIN SECRETION IN
MOTHERS
Melinda Cservenák, Ibolya Bodnár, György M. Nagy, Ted B. Usdin, Miklós Palkovits,
Árpád Dobolyi
158
P/II-3
OPTOGENETIC APPROACH FOR INVESTIGATION OF NEURONAL
MATURATION
Tímea Kőhidi
159
P/II-4
ALTERED DEVELOPMENT OF HYPOTHALAMUS IN INTRAUTERINE
UNDER NOURISHED RATS MAY CONTRIBUTE TO METABOLIC
DISORDERS IN ADULTHOOD
Katalin Könczöl, Miklós Palkovits, Zsuzsanna E. Tóth
160
P/II-5
PHARMACOGENOMICAL SIGNIFICANCE OF MITOCHONDRIAL DNA
SUBSTITUTIONS
Viktória Reményi, György Máté Milley, Gábor Nyírő, Anikó Gál, Mária Judit Molnár
161
16
2012. április 12-13.
P/III POSTER PRESENTATIONS
Chairman: Prof. Dr. Péter Lakatos
P/III-1
CAN HUMAN DNA ACTIVATE IMMUNE CELLS VIA TLR9?
CYTOKINE PROFILE OF HT-29 CELLS TREATED WITH HUMAN DNA
ISOLATED FROM HUMAN CANCER CELLS
István Fűri, Sándor Spisák, Árpád V. Patai, Ferenc Sipos, Barnabás Wichmann, Orsolya
Galamb, Gábor Valcz, Alexandra Kalmár, Bálint Péterfia, Katalin Leiszter, Kinga Tóth,
Andrea Schöller, Barbara Kinga Barták, Zsófia Brigitta Nagy, Tibor Krenács, Béla Molnár,
Zsolt Tulassay
165
P/III-2
VENULAR DIAMETER REGULATORY ROLE OF THE VASCULAR
ENDOTHELIAL GROWTH FACTOR (VEGF) IN DIFFERENT CONDITIONS
OF RAT GINGIVA
Milán Gyurkovics, Zsolt Lohinai, Adrienne Győrfi, Csaba Bodor, Andrea Dorottya Székely,
Elek Dinya, László Rosivall
166
P/III-3
GENE EXPESSION-BASED ANALYSIS OF COLORECTAL DYSPLASIACARCINOMA TRANSITION
Alexandra Kalmár, Orsolya Galamb, Sándor Spisák, Barnabás Wichmann, Ferenc Sipos,
Tibor Krenács, Kinga Tóth, Katalin Leiszter, Andrea Schöller, István Fűri, Zsófia Brigitta
Nagy, Barbara Kinga Barták, Zsolt Tulassay, Béla Molnár
167
P/III-4
RENIN-ANGIONTENSIN-ALDOSTERONE-SYSTEM BLOCKERS IN
DIABETIC NEPHROPATHY: THE ROLE OF THE SIGMA-1 RECEPTOR
Lilla Lénárt, Nóra Fanni Bánki, Ágota Vér, László Wagner, Ágnes Prókai, Sándor Kőszegi,
Ádám Hosszú, Attila Szabó, Andrea Fekete
168
P/III-5
INVESTIGATION OF THYMIDYLATE SYNTHASE GENE POLYMORPHISM
IN COLON CANCER PATIENTS
Andrea Schöller, Alexandra Kalmár, Árpád V. Patai, Zsófia Nagy, Barbara Barták, Orsolya
Galamb, Sándor Spisák, Lídia Sréter, Béla Molnár, Zsolt Tulassay
169
P/III-6
COGNITIVE FUNCTION IN PATIENTS WITH TYPE 1 DIABETES
Barbara Szémán, Géza Nagy, Anna Veres-Székely, Mária Sasvári, Dávid Fitala, Adrienn
Szöllősi, Orsolya Hadarits, Zahra Al-Aissa, Anikó Somogyi
170
P/III-7
DETECTION OF METHYLATED SEPT9 PERIPHERAL BLOOD SCREENING
MARKER IN BOTH LEFT - AND RIGHT - SIDED COLON CANCER AND
COMPARISON TO FOBT AND CEA
Kinga Tóth, Jürgen Beck, Kerstin Buser, Zsófia Brigitta Nagy, Barbara Kinga Barták, Robert
Stöhr, Henriette Golcher, Vera Schellerer, Zsolt Tulassay, Béla Molnár
171
P/IV POSTER PRESENTATIONS
Chairman: Dr. Attila Patócs
P/IV-1
THE COMPACT MUTATION OF MYOSTATIN CAUSES SKELETAL MUSCLE
HYPERPLASIA
Júlia Baán, Tamás Kocsis, Anikó Keller-Pintér, Luca Mendler, László Dux
175
P/IV-2
A NOVEL BURSAL STEM CELL ANTIGEN: CHARACTERIZATION AND
ONTOGENIC STUDY
Nóra Fejszák
176
17
P/IV-3
EFFECT OF THE COMPACT MUTATION ON THE GLYCOGEN CONTENT
OF SKELETAL MUSCLE
Tamás Kocsis, Júlia Baán, Luca Mendler, Anikó Keller-Pintér, László Dux
177
P/IV-4
EFFICIENCY OF TRANSFECTION ALONG THE REGENERATING SOLEUS
MUSCLE
Magdolna Kósa, Ernő Zádor
178
P/IV-5
MISPLACED PHOTORECEPTORS DURING POSTNATAL DEVELOPMENT
IN THE RAT RETINA
Klaudia Szabó, Arnold Szabó, Anna Énzsöly, Ágoston Szél, Ákos Lukáts
179
P/IV-6
META-ANALYTIC COMPARISON OF PROTEOMIC DATA ON
EXTRACELLULAR VESICLE SUBSETS
Tamás G. Szabó, Petra Misják, Borbála Aradi, Bence György, Mária Pásztói, Zsuzsanna Pál,
Krisztina Pálóczi, Valéria László, Éva Pállinger, Erna Pap, Ágnes Kittel, K. Taylor-Szabó,
György Nagy, András Falus, Edit Buzás
180
P/V POSTER PRESENTATIONS
Chairmen: Dr. Lajos Simon, Dr. Katalin Hegedűs, Dr. György Purebl
P/V-1
POST-ERROR SLOWING IN PATIENTS WITH ATTENTION
DEFICIT/HYPERACTIVITY DISORDER (ADHD) - A META-ANALYSIS
Lívia Balogh, Szilvia Papp, László Tombor, István Bitter, Pál Czobor
183
P/V-2
THE ROLE OF CYP POLYMORPHISMS IN THE THERAPEUTIC EFFECT
AND ADVERSE REACTIONS OF PSYCHOTROP DRUGS
Dóra Filipovits, Gábor Csukly, István Bitter
184
P/V-3
SUICIDE PREVENTION. THE FAMILY MEMBER'S POSSIBILITIES AND
RESPONSIBILITY
Győző Orbán
185
P/V-4
SOCIO-CULTURAL INFLUENCES ON BODY IMAGE DISSATISFACTION IN
ADOLESCENCE
Ildikó Papp, Edit Czeglédi, Bernadett Babusa, Ferenc Túry
186
P/V-5
CONDUCTING CROSS-DISORDER WHOLE-GENOME ASSOCIATION
STUDIES: LIMITATIONS AND SOLUTIONS
Attila J. Pulay, János Réthelyi
187
P/V-6
IS DREAMING MERELY A COGNITIVE PERFORMANCE?
ANALYSIS OF THE CONTENT AND NARRATIVE STRUCTURE OF
CHILDREN’S DREAMS
Piroska Sándor, Sára Szakadát, Orsolya Péntek, Róbert Bódizs
188
P/V-7
STUDY OF FEEDBACK-DRIVEN REINFORCEMENT LEARNING IN
SCHIZOPHRENIA
Zsuzsanna Somlai, Szabolcs Kéri
189
P/V-8
EXPERIENCES WITH CHAT COMMUNICATION IN MAINTENANCE
TREATMENT FOR PATIENTS WITH BULIMIC SYMPTOMATOLOGY
Ágnes Mezei, Hayriye Güleç, Markus Moessner, Elisabeth Kohls, Ferenc Túry
190
18
2012. április 12-13.
P/V-9
AFFECTIVE TEMPERAMENT PROFILE IN PATIENTS WITH
HYPERTENSION. FIRST RESULTS WITH TEMPS-A IN PRIMARY CARE IN
HUNGARY
Ajándék Eőry, Péter Torzsa, Xénia Gonda, László Kalabay, Zoltán Rihmer
191
P/V-10
EFFECTS BETWEEN DONATION ATTITUDE AND DONATION ACTIVITY
IN HUNGARIAN INTENSIVE CARE UNITS
Sándor Mihály
192
P/VI POSTER PRESENTATIONS
Chairman: Prof. Dr. József Tímár
P/VI-1
RTF1 GENE IN CARBOPLATIN RESISTANT OVARIAN CANCER
Zsófia Pénzváltó, András Lánczky, Balázs Győrffy
195
P/VI-2
ß-CATENIN, TRICELLULIN AND EZH2 DIFFERENTIATE FETAL AND
EMBRYONAL COMPONENTS IN EPITHELIAL HEPATOBLASTOMA
Kriszta Schlachter, Mónika Gyugos, Gábor Lotz, Ilona Kovalszky, Kornélia Baghy, Péter
Nagy, Gábor Lendvai, András Kiss, Zsuzsa Schaff
196
P/VI-3
ASSOCIATION BETWEEN THE INCIDENCE OF LYME DISEASE AND
TEMPERATURE IN HUNGARY, 1998-2010
Attila Trájer, János Bobvos, Katalin Krisztalovics, Anna Páldy
197
P/VI-4
TUMOR CELLS AND CARCINOMA-ASSOCIATED FIBROBLASTS
INTERACTION REGULATES MATRIX METALLOPROTEINASES AND
THEIR INHIBITORS IN ORAL SQUAMOSUS CELL CARCINOMA
Alexandra Fullár, József Dudás, Ilona Kovalszky
198
P/VI-5
MICRORNA EXPRESSION DIFFERS IN EMBRYONAL AND FETAL
SUBTYPES OF EPITHELIAL HEPATOBLASTOMAS
Mónika Gyugos, Krisztina Schlachter, Gábor Lotz, Ilona Kovalszky, Kornélia Baghy, Péter
Nagy, András Kiss, Zsuzsa Schaff, Gábor Lendvai
199
P/VI-6
THE ROLE OF DIABETES AND ANTIDIABETIC DRUGS IN PANCREATIC
FIBROSIS AND CANCER
Katalin Kiss, Gábor Firneisz, Ilona Kovalszky
200
P/VII POSTER PRESENTATIONS
Chairman: Dr. István Antal
P/VII-1
THE HIGHLY SELECTIVE µ-OPIOID AGONIST PEPTIDE DAMGO SHOWED
PREDOMINANTLY PERIPHERAL ANALGESIA IN RAT VISCERAL PAIN
MODEL
Erzsébet Lackó, Pál Riba, Melinda Sobor, Júlia Timár, Shaaban A. Mousa, Michael Schäfer,
Susanna Fürst, Mahmoud Al-Khrasani
203
P/VII-2
EFFECT OF NATIVE AND OLIGOTUFTSIN CONJUGATED W-SEWSPEPTIDES ON THE ADHESION AND MIGRATION OF TUMOR CELL LINES
Júlia Láng, Katalin Pomázi, László Kőhidai
204
P/VII-3
CHARACTERIZATION OF DRUG CARRIERS SYSTEMS WITH DIFFERENT
HLB VALUES
Noémi Anna Niczinger, Lívia Budai, Mária Hajdú, Judit Dredán, István Antal
205
19
P/VII-4
DEVELOPMENT OF A MULTIPARTICULATE DRUG DELIVERY SYSTEM
FOR PETROSELINUM CRISPUM EXTRACT
Zsófia Edit Pápay, Emese Balogh, Annamária Kósa, Ákos Ruszkai, Imre Boldizsár,
István Antal
206
P/VII-5
OPTIMIZATION OF A SIMPLE CAPILLARY ELECTROPHORESIS METHOD
FOR THE SEPARATION OF TWELVE QUINOLONE DERIVATIVES
Aura Rusu, Gabriel Hancu, Gergő Tóth, Gergely Völgyi, Béla Noszál, Árpád Gyéresi
207
P/VII-6
SELECTIVITY PROFILING OF FGF RECEPTOR INHIBITORS
Zsákai Lilian, Németh Gábor
208
AUTHORS AND TITLES OF ABSTRACTS
(LISTED UNDER THE CORRESPONDING DOCTORAL SCHOOLS)
20
209
2012. április 12-13.
E/I
ORAL PRESENTATIONS
Chairman:
Prof. Dr. Zoltán Benyó
21
22
2012. április 12-13.
E/I-1
TRANSIENT OUTWARD POTASSIUM CURRENT IN DOG ATRIAL
PREPARATIONS
Claudia Corici1, Zsófia Kohajda2, Attila Kristóf2, Tamás Szél1, Zoltán Husti1, István Baczkó1,
András Varró 1,2, László Virág1,2, Norbert Jost1,2
1
2
Department of Pharmacology and Pharmacotherapy, University of Szeged
Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged
Repolarization in cardiac muscle is controlled by a fine balance of several inward and outward transmembrane
ionic currents and electrogenic pump mechanisms. The aim of the present study was to investigate the role of
transient outward potassium current (Ito) in atrial repolarization. Ito current was recorded by the whole-cell
configuration of the patch clamp technique. Large Ito current was observed in dog atrial myocytes. The current
amplitude was 15.2±1.1 pA/pF at 50 mV (n=11). The inactivation phase of the current was best fitted by two
exponentials (fast time constant: 11.3±1.2 ms, fast amplitude: 10.4±0.8 pA/pF; slow time constant: 116.1±8.2
ms, slow amplitude: 3.7±0.5 pA/pF; n=10, test potential: 50 mV). Ito current during the action potential plateau
phase was measured as chromanol 293B sensitive current, which drug effectively suppressed not only the slow
delayed rectifier potassium current but also Ito. An atrial action potential waveform was used for the command
potential. It was found that Ito carries large outward current in the plateau phase of the atrial action potential. The
effects of Ito blockade on the action potential repolarization were also investigated in dog atrial muscle by the
conventional microelectrode technique. The current was inhibited by application of 100 µM chromanol 293B.
The drug increased the plateau potential but failed to lengthen the action potential in atrial preparations.
However, the Ito is large during the plateau phase, blockade of the current did not lengthen the action potential in
dog atrial muscle. Thus, understanding the role of transient outward potassium current in atrial repolarization
requires further investigations.
Doctoral School: MultidisciplinaryMedicine
Program: Biochemistry, biophysics, molecular and cell biology
Supervisor: Nándor Jost
E-mail: [email protected]
23
E/I-2
LATEST RESULTS OF THE RESPIRATORY ASPECTS OF THE
INTERNATIONAL TWIN STUDY
David Laszlo Tarnoki1, Adam Domonkos Tarnoki1, Emanuela Medda2, Levente Littvay3,
Zsofia Lazar4, Rodolfo Cotichini2, Corrado Fagnani2, Maria Antonietta Stazi2, Lorenza Nisticó2,
Pierleone Lucatelli5, Emanuele Boatta5, Chiara Zini5, Fabrizio Fanelli5, Claudio Baracchini6,
Giorgio Meneghetti6, Akos Koller7, Janos Osztovits8, Gyorgy Jermendy8, István Préda9,10,
Róbert Gábor Kiss9,10, Kinga Karlinger1, Agnes Lannert11, Giuseppe Schillaci12,
Andrea Agnes Molnar9,10, Zsolt Garami13, Viktor Berczi1, Ildiko Horvath4
1
2
3
4
5
6
7
8
9
10
11
12
13
Department of Radiology and Oncotherapy, Semmelweis University, Budapest
Istituto Superiore Di Sanitá, Italian Twin Registry, Rome, Italy
Central European University, Budapest
Department of Pulmonology, Semmelweis University, Budapest
Vascular and Interventional Radiology Unit, Department of Radiological Sciences, La Sapienza
University of Rome, Rome, Italy
Department of Neurosciences, School of Medicine, University of Padua, Padua, Italy
Department of Pathophysiology and Gerontology, University of Pécs
Bajcsy Zsilinszky Hospital, 3rd Department of Internal Medicine, Semmelweis University,
Budapest
Research Group for Inflammation Biology and Immunogenomics of Hungarian Academy of
Sciences and Semmelweis University, Budapest
Department of Cardiology, State Health Center, Budapest
Semmelweis University, School of Pharmacy, Budapest
Unit of Internal Medicine, Department of Clinical and Experimental Medicine, University of
Perugia at Terni, Terni, Italy
The Methodist Hospital, DeBakey Heart and Vascular Center, Houston, TX, USA
Introduction : Nitric oxide, measured by fractional exhaled nitric oxide (FENO), has an important modulatory
role on the structure and function of the airways and vessel walls. The role of genetic factors on nicotine
dependence is well understood, however no information is available on secondhand smoke (SHS) exposure
sensibility.
Methods: 117 adult Hungarian, Italian and American twin pairs (83 monozygotic, MZ and 34 dizygotic, DZ
pairs; age: 48±16 SD years) underwent FENO measurement by an electrochemical sensor-based device. Markers
of arterial stiffness (brachial and aortic augmentation index, Aixbra, Aixao; aortic pulse wave velocity, PWVao) were
determined by oscillometric method (Arteriograph). Bivariate Cholesky decomposition models were applied. 161
Hungarian and 50 American twin pairs (151 monozygotic and 62 dizygotic; age: 44±17 years) replied to our
questionnaire concerning smoking characteristics and SHS exposure.
Results : Genetic effects accounted for 59% (95% confidence interval, CI, 43-71) of the FENO variation.
Significant negative correlation was observed between FENO and Aixbra (r=-0.20; 95%CI:-0.34,-0.05), or Aixao (r=0.19; 95%CI:-0.33,-0.05). No significant correlation was found between FENO and PWVao. Genetic factors
explained the entire phenotypic correlation between FENO and Aixbra or FENO and Aixao. FENO showed a
significant negative genetic correlation with Aixbra and Aixao (rg=-0.29; 95%CI:-0.49,-0.07). Higher concordance
was found in the disturbing effect of SHS in MZ versus DZ pairs (58 to 94% versus 39 to 79%, p<0.05 to
p<0.005). Smaller difference was observed in self-reported smoke pollution rate in MZ compared to DZ pairs
concerning the restaurants and cafés (1.2±1.3 vs 1.8±1.5, p<0.05) which was not present regarding restaurants,
cafés and transportation facilities.
24
2012. április 12-13.
Conclusions : FENO variations are explained by genetic and non-shared environmental effects. Covariances
between FENO and Aix are explained entirely by genetic factors providing a basis for further studies on
cardiovascular and respiratory diseases. Genetic influence on smoking habits and secondhand smoke sensibility
was estimated.
Doctoral School: Basic Medicine
Program: Mechanism of normal and pathological functions of the circulatory system
Supervisor: Ildiko Horvath, Viktor Bérczi
25
E/I-3
SOPHISTICATED ARRHYTHMIA DETECTION WITH 256-SLICE CT
ALLOWS DIAGNOSTIC CORONARY ARTERY IMAGING IN PATIENTS
WITH ATRIAL FIBRILLATION
CORONARY CT ANGIOGRAPHY WITH 256-SLICE SCANNER IN
PATIENTS WITH ATRIAL FIBRILLATION
Mihály Károlyi, Andrea Bartykowszki, Erik Formanek, Mohammed Muhemin,
Csaba Csobay-Novák, Nándor Pintér, Kálmán Hüttl, György Balázs, Béla Merkely,
Pál Maurovich-Horvat
Heart Center, Semmelweis University, Budapest
Purpose: Atrial fibrillation (AF) is considered as a relative contraindication to coronary computed tomography
angiography (CCTA) due to the irregular heart rates resulting in motion artifacts. Thus, the aim of this study was
to evaluate the performance of 256-slice CCTA (256-CCTA) with sophisticated arrhythmia recognition software
for the visualization of coronary arteries in a population with atrial fibrillation and to explore the impact of
patients’ mean heart rate (HR) on image quality (IQ).
Methods: Thirty-six consecutive patients (25 male, 64.2±10.2 years old) with permanent AF were examined on
256-slice CT scanner (120 kV, 300 mAs/rot, 0.27 s rotation time, 2x128×0.625 mm collimation, Philips Brilliance
iCT) to evaluate the coronary arteries. Patients were divided into two groups: low/medium HR [LHR] group
(mean HR < 80 bpm, n=22) and high HR [HHR] group (mean HR≥80 bpm, n=14). The IQ assessment was
based on the American Heart Association's coronary segment classification scheme using a four-point likert-type
scale from excellent (1) to non-assessable (4).
Results: 467 coronary segments were analyzed. Mean IQ score was 1.9±0.7. 86.1% (402/467) of the segments
had diagnostic IQ, resulting in 50.3% (235/467) excellent, 25.9% (121/467) good and 9.9% (46/467) moderate
IQ. Image quality of LHR group was better than that of HHR group (mean score 1.6±0.6 versus 2.4±0.7;
p=0.0014). The mean HR of LHR group and HHR group were 68.5±8.5 beats per minute (bpm) and 94.6±12.7
bpm (p<0.0001). There was no difference between the range of the variation of HR between the LHR group and
HHR group (mean difference between minimum and maximum HR: 53.1±26.9 versus 63.1±35.8 bpm; p=0.34).
The average radiation dose was 6.9±2.6 mSv (range: 3.5-15.0 mSv).
Conclusion: Due to the sophisticated arrhythmia detection algorithm, wide detector coverage and high temporal
resolution of the 256-slice CT, it provides diagnostic image quality in patients even with AF, which should
otherwise be considered as a contraindication to CCTA examinations. Patients’ mean HR has a significant impact
on IQ. The radiation dose of 256-CCTA in AF is lower than that of other CCTA in AF.
Doctoral School: Basic medicine
Program: Physiology and clinics of the heart and coronary diseases
Supervisor: Béla Merkely
26
2012. április 12-13.
E/I-4
THE ROLE OF MICRORNAS IN RENAL ISCHEMIA-REPERFUSION
INJURY
Institute of Pathophysiology, Semmelweis University, Budapest
Introduction: Ischemia induced acute tubular necrosis (ATN) is one of the main causes of acute kidney injury.
Reperfusion paradoxically increases the injury due to apoptotic processes. The modulation of pro-apoptotic
genes is currently under investigation. MicroRNAs are posttranscriptional regulators of gene-expression. Our aim
was to investigate the miRNA expression profile and to elucidate their role in ischemia-reperfusion (IR) induced
ATN.
Methods: At 1, 3, 6, 15, 24 and 48 hours after unilateral renal ischemia of C57BL/6 mice, renal function (urea)
and morphology (PAS stain, NGAL) were assessed. The miRNA expression profile was evaluated at 24 hours
post-ischemia (Luminex multiplex assay). MiRNA expression pattern was analyzed during the reperfusion phase
(real-time PCR) at the above time-points. Renal cell proliferation was evaluated by CyclinD1
immunohistochemistry on tissue microarray slides.
Results: Three miRNAs (miR-21, miR-17-5p and miR-106a) were significantly elevated in IR injury after 24
hours of reperfusion (3.0, 1.5 and 1.4 fold, respectively, p<0.05). Real-time PCR analysis demonstrated, that these
miRNAs started to elevate after 24 hours of reperfusion further increasing at 48 hours (miR-21: 2.3 fold, p<0.01;
miR-17: 2.2 fold, p<0.01; miR-106a, 1.9 fold, p<0.01). Renal histology was pathologic already at 1, blood urea
started to elevate at 3, renal NGAL mRNA at 6 and plasma NGAL at 15 hours. CyclinD1 nuclear staining
decreased significantly after 1 hour (0.51 fold, p<0.01), but returned to control values at 48 hours of reperfusion,
suggesting improvement in renal tubular cell proliferation during this phase of IR injury.
Conclusion: We identified three miRNAs with altered expression in IR injury, prior to amelioration of renal
tubular cell proliferation. Validated targets of the identified miRNAs have mostly pro-apoptotic effects.
Therefore our results suggest that these miRNAs may be involved in the regeneration processes and could
represent possible therapeutic tools in the treatment of ATN.
Support: OTKA:K81972
Acknowledgements: Dr. Tibor Krenács, 1st Department of Pathology and Experimental Cancer Research
Program: Physiology and pathophysiology of the regulation of fluids and electrolyte homeostasis
Supervisor: Péter Hamar
27
E/I-5
ISOLATION AND CULTURE OF RAT BONE MARROW
MESENCHYMAL STEM CELLS
Introduction : Mesenchymal stem cells are a promising opportunity for the treatment of myocardial infarction
and can be isolated from the bone marrow of several species. Our aim was to isolate mesenchymal stem cells
from rat bone marrow, to cultivate them in standard conditions and to characterize the cells with cell surface
markers.
Materials and methods : Mesenchymal stem cells were isolated from male Sprague-Dawley rats according to the
protocol described by Caplan et al. Briefly, cells were gained from the marrow of the femurs and tibia and
centrifuged at 450 g for five minutes. Cells were planted in 25cm2 flasks at optimum seeding density in alphaMEM, 10% FBS, 1% penicillin-streptomycin and 1% fungizone (amphotericin B). The medium was changed
after 24 hours to remove non-adherent cells. Third passage cells were used for characterization. Cell surface
markers CD 90 and CD 45 were used for immunostaining.
Results: We were able to isolate and cultivate rat bone marrow mesenchymal stem cells and to maintain the
culture for three passages. The cells adhered to plastic, were able to proliferate and demonstrated typical
mesenchymal stem cell-like morphological features. The cells were triangle-shaped with elongated extensions at
the beginning of cultivation and later on they showed spindle-shaped morphology. The cells stained positive for
CD 90, which is one of the mesenchymal stem cell markers, and negative for CD 45 thereby were free of
hematopoietic cells.
Discussion: We were able to isolate and culture mesenchymal stem cells from rat bone marrow. Our future aim
is to develop cardiomyocytes from human mesenchymal stem cells in vitro and to evaluate factors which can
enhance the efficacy of cardiomyocyte transdifferentiation
Doctorial School: Basic Medicine
28
2012. április 12-13.
E/I-6
CARDIOPULMONARY BYPASS IMPAIRS BRAIN OXYGENATION AS
DEMONSTRATED BY NEAR-INFRARED SPECTROSCOPY
Peter Mukli
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University,
Budapest
Introduction: Cerebral oxygenation is a tightly regulated, complex phenomenon. At awake rest and under
pulsatile conditions, oxy- and deoxyhemoglobin (HbO2, HHb) levels in the prefrontal cortex (PFC)
spontaneously fluctuate in anticorrelated manner due to the impact of neural activity, as demonstrated earlier.
Oxygenation of the brain cortex may be impaired during non-pulsatile cardiopulmonary bypass (NP-CPB) tuned
to the lower limit of cerebral autoregulation (LL-CA). If so, a mismatch between O2 supply and O2 consumption
may well play a role in the frequent and serious complication of NP-CPB surgeries, termed post-operative
cognitive dysfunction (POCD).
Objective: Is the autoregulation and this complex fluctuation pattern maintained under extracorporeal nonpulsatile brain perfusion?
Methods: Patients (5 male, 5 female, 70±7.5 years) underwent NP-CPB surgery in the Department of Cardiac
Surgery, Semmelweis University. Our study observed the established protocols. The cardiac index of NP-CPB
was 2.4 L/min/m2 and the MAP was targeted at 50-70 Hgmm. The changes of Hb-concentrations were recorded
in 16 regions of the PFC by our NIRS-LEDI equipment at 3 Hz. Groups were created in control (C), before
(*M), during (M), and after NP-CPB (M*). Tissue O2-saturation (StO2[%]) was calculated from [∆HbO2] and
[∆HHb], the cross-correlation coefficient (rHb) between [∆HbO2] and [∆HHb]. rHb structuring was characterized
by their spectral index (β).
Results: StO2[%] decreased as the anticorrelation in rHb fluctuation disappeared during extracorporeal circulation
(Table 1.). NP-CPB changed the spectral structuring from correlated noise to near random noise, and then to
antipersistent motion.
Groups
C
*M
M
M*
p
#
StO2[%]
-0.41±0,02
0.33±0,06#
-0.42±0.07
p<0.05
rHb
-0.59±0.20
-0.50±0.21
0.04±0.11& -0.51±0.18 &p<0.0001
0.63±0.24
0.58±0.12
0.18±0.13§
1.20±0.25§ §p<0.0001
β of rHb
Table 1. Results are presented as mean ± S.D. and compared with repeated measures ANOVA (Newman-Keuls post hoc test)
Discussion: Impairment of cerebral oxygenation should be considered when NP-CPB is performed in elderly
patients with a likely elevated LL-CA. Since rHb reflects the dynamics, and β reflects the structuring of oxygen
equilibration in tissue, our results imply that NP-CPB severely disturbed the O2-diffusion profiles in the brain
cortex due to impaired cerebral autoregulation, which can contribute to POCD.
Program: Mechanisms of normal and pathologic functions of the circulatory system
Supervisors: András Eke
29
E/I-7
PREDICTORS OF CRT-INDUCED LEFT VENTRICULAR REVERSE
REMODELING
Vivien Klaudia Nagy, Valentina Kutyifa, Astrid Apor, Csilla Liptai, Eszter Édes, Gábor Széplaki,
Béla Merkely
Background: Cardiac Resynchronisation Therapy (CRT) is improving clinical status and inducing left ventricular
(LV) reverse remodeling in selected heart failure patients. However, one third of patients are non-responders
showing no improvement from treatment.
Aim: Identifying parameters to predict favorable echocardiographic response to CRT.
Methods: LV remodeling was defined as a decrease of ≥ 15% in LV end-systolic volume.
Echocardiography data of 73 consecutive CRT patients (mean age 67±11 yrs; 60 men) were investigated before
device implantation and during the six-month follow-up. LV volumes, systolic function, pulmonary artery systolic
pressure (PASP) and the grade of mitral regurgitation (MI) were evaluated. Clinical characteristics and renal
function were also assessed at baseline.
Results: CRT therapy was associated with significant improvement in LV ejection fraction (28,8±5,9 vs.
38,7±8,6%, p<0,001) decrease in LV end-diastolic (247±71 vs. 214±76 ml, p=0,006), end-systolic volume
(177±56 vs. 136±61 ml, p<0,001), PASP (30±15 vs. 25±12 Hgmm, p=0,044) and grade of MI (1,9±1 vs.
1,4±0,9, p=0,001). We investigated potential clinical (age, QRS, NHYA class, etiology of heart failure, baseline
urea level) and echocardiographic predictors (LV ejection fraction, LA volume, grade of MI, PASP) in an
echocardiography response model using best subset regression analysis. After selection of best model multivariate
analysis revealed baseline urea level (HR=0.93, 95% CI: 0.88-1.00, p=0,042) to be an independent predictor of
echocardiographic response.
Conclusions: CRT is associated with significant improvement in LV systolic function, diameters, MI and PASP.
Baseline urea level is an independent predictor of CRT-induced LV reverse remodeling in our patient population.
The scientific project was granted by TÁMOP 4.2.2.-08/1/KMR-2008-00 and NKTH-OTKA K687924.
30
2012. április 12-13.
E/I-8
LATEST RESULTS OF THE CARDIOVASCULAR AND
ANTHROPOMETRIC ASPECTS OF THE INTERNATIONAL TWIN
STUDY
Adam Domonkos Tarnoki1, David Laszlo Tarnoki1, Emanuela Medda2, Maria Antonietta Stazi2,
Rodolfo Cotichini2, Corrado Fagnani2, Lorenza Nisticó2, Pierleone Lucatelli3, Emanuele Boatta3,
Chiara Zini3, Fabrizio Fanelli3, Claudio Baracchini4, Giorgio Meneghetti4, Janos Osztovits5,
Gyorgy Jermendy5, István Préda6,7, Róbert Gábor Kiss6,7, Levente Littvay8, Julia Metneki9,
Tamas Horvath10, Kinga Karlinger1, Agnes Lannert12, Andrea Agnes Molnar6,7, Zsolt Garami13,
Pal Bata1, Gyorgy Baffy14, Giuseppe Schillaci15, Viktor Berczi1
1
2
3
4
5
6
7
8
9
10
12
13
14
15
Department of Radiology and Oncotherapy, Semmelweis University, Budapest
Genetic Epidemiology Unit, National Centre of Epidemiology, Istituto Superiore di Sanità, Rome,
Italy
Vascular and Interventional Radiology Unit, Department of Radiological Sciences, La Sapienza
University of Rome, Rome, Italy
Department of Neurosciences, School of Medicine, University of Padua, Padua, Italy
Bajcsy Zsilinszky Hospital, III. Department of Internal Medicine, Semmelweis University,
Budapest
Department of Cardiology, State Health Center, Budapest
Central European University, Budapest
National Centre for Healthcare Audit and Inspection, Budapest
Budapest
Semmelweis University, Faculty of Pharmacy, Budapest
The Methodist Hospital DeBakey Heart and Vascular Center, Houston, TX, USA
Department of Medicine, VA Boston Healthcare System, Boston, MA, USA
Unit of Internal Medicine, Department of Clinical and Experimental Medicine, University of
Perugia at Terni, Terni, Italy
Introduction : Central blood pressure, aortic stiffness, pathological body composition and nonalcoholic fatty
liver disease (NAFLD) have been consistently reported as cardiovascular risk factors.
Methods: 154 monozygotic (MZ) and 42 dizygotic (DZ) twin pairs (age 43±17 years) from Hungary and the
United States underwent brachial and central augmentation index (AIx), brachial and central pressure, and aortic
pulse wave velocity (PWV) measurements with the invasively validated Arteriograph (Medexpert Ltd, Budapest).
Bivariate Cholesky decomposition models were applied. 380 Hungarian, Italian and American twin pairs (230
MZ, 150 DZ pairs; age 49.1±15.4 years) participated in body composition measurement by using bioelectrical
impedance analysis (OMRON BF500). Ultrasonography was performed to detect steatosis and categorize severity
on 208 Hungarian twins (63 MZ, 41 DZ pairs; age 43.7±16.7 years). Carotid intima-media thickness (IMT) was
also measured.
Results : Age-, sex- and country-adjusted heritability was 60% for central systolic blood pressure (SBP) (95%
confidence interval /CI/, 45-70), 50% for aortic PWV (95%CI, 26-67), 49% for aortic AIx (95%CI, 2-74), 47%
for brachial AIx (95%CI, 1-74), 47% for central pulse pressure (PP) (95%CI, 12-61), 30% for brachial PP
(95%CI, 0-53), 82% for weight (95%CI: 78-85), 74% for waist and hip circumferences (95%CI: 68-79), body fat
percentage (95%CI: 69-79) and fat-free mass (95%CI: 69-79), and 79% for body mass index (95%CI: 74-83). No
31
discernible role for genetic components in the presence of NAFLD was indicated (95%CI, 0-36). Augmentation
indices and carotid IMT in twins with NAFLD were increased at most examined locations (p<0.05 to p<0.001).
Genetic factors explained a moderate phenotypic correlation between central PP, SBP, brachial SBP and aortic
PWV.
Conclusions : Central and brachial pulse pressures and arterial stiffness are moderately heritable. A moderate
genetic covariance among aortic PWV and central PP, SBP and brachial SBP was found. Strong heritability of
anthropometric parameters but no heritability of NAFLD was found.
Program: Cardiovascular disorders: physiology and medicine
Supervisors: Viktor Bérczi
32
2012. április 12-13.
E/I-9
TWELVE-HOLES GOLD ELECTRODE ABLATION CATHETER
PROVED TO BE EFFECTIVE AND SAFE ALSO AT REDUCED
IRRIGATION FLOW RATE
Eszter Mária Végh1, Endre Zima1, Tamás Szili-Török2, Gábor Széplaki1, Márta Hubay3,
Luc Jordaens2, László Gellér1, Béla Merkely1
1
2
3
Erasmus MC, Rotterdam, The Netherlands
Department of Forensic Medicine, Semmelweis University, Budapest
Keywords: radiofrequency ablation, catheter irrigation, ablation safety, animal model
At radiofrequency ablation (RF) in heart failure patients amount of irrigation fluid can be an important
consideration. A novel, 12-holes, gold electrode was investigated at regular and reduced irrigation flow rate. We
have hypotized, that the gold catheter can be applied as effective and safe at reduced irrigation flow rate as a
standard catheter.
Methods: 5 mongrel dogs’ thigh muscle was prepared, by raising of skin edges cradle was formed, that was
flushed with blood during ablation application (37 °C, 250 ml/min). The catheters were tested in perpendicular
and in paralell orientation at 8 and 15 ml/min irrigation flow; the contact force was 10g, the RF power was 30W
for 60 sec. Temperature of the catheter, coagulum formation and steam pops were recorded and lesion volumes
(V) were determined by histology. The AlCath Flux eXtra Gold (Au), 12-holes catheter was compared to AlCath
Flux FullCircle (PtIr) (Biotronik, Berlin, Germany) 6-holes catheter (both 7F, 3.5mm).
Results: Coagulum was not found on the catheter or on muscle surface. Between the occurence of steam-pops
and irrigation flow rate there was not significant connection. At reduced irrigation the Au catheter resulted larger
lesions compared to PtIr: at 8ml/min flow rate in paralel orientation VAu 861 vs VPtIr 504 mm³; in
perpendicular VAu 908 vs VPtIr 629 mm³. Temperature of Au catheter remained lower, than temperature of PtIr
(parallel 39.4 vs. 53.8 °C, perpendicular 42.1 vs. 46.7 °C).
Conclusion: The irrigation flow rate can be reduced without compromising ablation safety at these catheters,
while Au catheter performes larger lesion at minor warming. Reduction of irrigation may be beneficial at heart
failure patients’ long procedures due to prevention of fluid overload.
Supervisors: László Gellér
33
34
2012. április 12-13.
E/II
ORAL PRESENTATIONS
Chairman:
Dr. Gábor Békési
35
36
2012. április 12-13.
E/II-1
REGULATION OF GENE TRANSCRIPTION BY GLUCOCORTICOID
RECEPTOR (GR) ΒETA-ISOFORM
Bence T. Ács1,2, István Likó3, Karolina Feldman1,2, Péter M Szabó2, Henrietta Butz2, Károly Rácz2,
Attila Patócs4,5
1
2
3
4
5
2nd Department of Medicine, Semmelweis University, Budapest
2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest
Gedeon Richter Ltd., Budapest
2nd Department of Medicine and Molecular Medicine Research Group, Hungarian Academy of
Sciences, Semmelweis University Hungarian Academy of Sciences, Budapest
Laboratory Medicine Institute, Semmelweis University, Budapest
Introduction: Glucocorticoid acts trough glucocorticoid receptor (GR). Two isoforms of the GR: GRα and
GRβ with potential effect on gene transcription have been described. GRβ differing in C-terminal region from
GRα does not bind ligands and it has been shown to act as a dominant-negative inhibitor of GRα's
transactivational properties. Its potential pathological role has been revealed in steroid resistant states where its
increased expression has been reported.
Aims: Developing an in vitro model for evaluation of the GRβ related transcriptional regulation relevant in
development of steroid resistance.
Material and Methods: Caco-2 intestinal cell line was used for developing of the GRß stable expressing cell
line. GRß was cloned form the GRα isoform into mammalian expression pcDNA3.1-V5-His-TOPO vector. The
plasmids verified by direct DNA sequencing were transfected into Caco-2 cell line and clonal selection was
performed with neomycin treatment. The GRβ expression was confirmed by quantitative real time PCR and
Western blot analyses. Gene expression profiles of both the basic Caco-2 and the Caco-2-GRß was evaluated
using Agilent44K cDNA microarrays in basal and after Dexamethasone treatment (Dex, 100 nmol) for 8 h.
Results: GRα/GRβ ratio on mRNA level was 1:0.6 vs. 1:0.001 in Caco-2GRβ cells compared to the wild type
Caco-2 cells. 1048 transcripts were differentially (237 under- and 811 over-) expressed in Caco-2-GRß cells
compared to the basic Caco-2 cell line. Dex. treatment affected the expression of 132 (85 up and 47 down) genes
of these 48 of 85 and 8 of 47 genes were significantly altered in Caco-2GRβ as well. Gene set enrichment analysis
(GSEA) showed that an inhibition of genes containing consensus site for E2F1 transcription factor, and an
overexpression of genes containing consensus site for androgen receptor (AR) and GR in Caco-2GRβ cells.
Conclusions: In Caco-2 cells similarly to HeLa cells GRβ may posses a dominant-negative effect of GRα
mediated gene transcription. Therefore Caco-2GRβ cell line is an ideal model for studying the pathomechanism
of steroid resistance in inflammatory bowel disease. GRβ isoform may influence the activity of E2F1 and/or AR
respectively.
Doctoral School: Clinical Medicine
Program: Hormonal regulatory mechanisms
Supervisor: Attila Patócs
37
E/II-2
THE MYCOBACTERIAL DUTPASE: BIOCHEMISTRY, PHYSIOLOGY
AND MOLECULAR INTERVENTION
Rita Hirmondo1, Ildiko Pecsi1, Anna Lopata1, Amanda C. Brown2, Tanya Parish2,
Beata G. Vertessy1, Judit Toth1
1
2
Institute of Enzymology, Hungarian Academy of Sciences, Budapest
Queen Mary University of London, Barts and the London School of Medicine and Dentistry,
London, E1 2AT, United Kingdom
Thymidine biosynthesis is an essential metabolic pathway, as dTTP is one of the nucleotide building blocks of
DNA. Three major pathways exist for dTTP synthesis in humans, while in mycobacteria only one of these is
present. This one involves the dUTPase reaction. In addition, the constantly produced dUTP needs to be
eliminated to prevent DNA uracilation. Therefore, dUTPase is also required to eliminate excess dUTP.
We aimed to investigate the significance of the dUTPase pathway in mycobacteria. More specifically, we wish to
relate the previously deciphered in vitro reaction mechanism of dUTPase to physiology in the living mycobacterial
cell.
Mycobacterium smegmatis was used as a fast growing model for mycobacterial thymidine biosynthesis. Marked allelic
replacement, growth assays and in vitro enzyme assays were used.
We found that mycobacterial dUTPase genes (dut) exhibit over 85% sequence identity and thimidylate
biosynthesis is highly conserved among mycobacterial species. Interestingly, mycobacterial dut has a genusspecific surface loop absent in the human dUTPase. The knock-out of dut resulted in lethality in M. smegmatis,
which could be reverted by complementation with the wild-type dut. We assayed complementation with four
dUTPase mutants with different in vitro characterized enzyme activity. Importantly, mutant dut lacking the genusspecific loop was enzimatically unaffected, but was unable to complement the lethal knock-out phenotype.
However, partially or fully inactive mutants having the genus-specific loop could revert lethality. Growth assays
are in progress to reveal the effect of decreased dUTPase activity on various stress conditions.
Our results prove that dut is essential in M. smegmatis and that essentiality is brought about by the mycobacteriumspecific dUTPase motif and not by the enzymatic activity. Therefore, we propose that targeting the
mycobacterium-specific motif will potentially yield an efficient, specific antimycobacterial treatment.
Doctoral School: Biology, ELTE
Program: Structural biochemistry
Supervisor: Laszlo Graf
E-mail: [email protected], [email protected]
38
2012. április 12-13.
E/II-3
ABSORPTION AND TENSILE STRENGTH OF CELL-COATED
SUTURES
Budapest
Cell transplantation seems to be a promising method to support tissue regeneration, but delivering cells into the
injured area is still an obstacle. Cells attached to surgical sutures as a delivery vehicle might be a solution for soft
tissues. In our previous work, we reached confluent cell layer on sutures. In this present study, we investigated
the modifications made on the original sutures by the preparation method.
Methods: Tensile strength was tested after each preparation step with an Instron 5566 mechanical testing
machine and maximal load was determined. In vivo absorption after three, five and seven weeks was investigated
in Wistar rats by calculating the cross sectional diameter and fiber number of sutures in muscle tissue.
Results: Tensile strength was significantly decreased after 168hours of incubation, but did not change after 48
hours of incubation or cell coating compared to the original suture. Suture absorption showed significant
decrease in cross-sectional diameter and fiber number after 168hours of incubation at 5 weeks. These differences
increased even further at 7 weeks. 48 hours of incubation had no significant difference from original sutures at
any time point.
Discussion: In our experiment we showed that elongated in vitro preparation time results in tensile strength
reduction and faster absorption of sutures which could be disadvantageous in surgical practice. Cell coated
sutures could still make a convenient cell transplantation method; by keeping the incubation time as low as
possible, one does not compromise original features, and also brings the clinical utilization closer.
Program: Physiology and pathology of the musculosceletal system
Supervisor: Zsombor Lacza
39
E/II-4
DETECTION OF EARLY GLAUCOMATOUS PROGRESSION WITH THE
RTVUE OPTICAL COHERENCE TOMOGRAPH AND SCANNING
LASER POLARIMETRY
Department of Ophthalmology, Semmelweis University, Budapest
Purpose: To compare the ability of RTVue-100 Fourier-domain optical coherence tomograph (RTVue-OCT)
and scanning laser polarimetry with variable (GDx-VCC) and enhanced (GDx-ECC) corneal compensation to
detect early glaucomatous progression.
Methods : One eye of 110 Caucasian patients (17 healthy, 20 ocular hypertensive, 22 pre-perimetric and 51
perimetric glaucoma eyes) were imaged prospectively in 6-month intervals for 1.5 to 3 years. Progression was
determined by Octopus normal G2 visual field progression criteria.
Results: Median visual field mean defect (MD) change was 0.914 dB/year in the controls, -0.303 dB/year in
perimetric glaucoma and -0.516 dB/year for the 10 functionally progressing perimetric glaucoma eyes. Relative
(%) variance of all retinal nerve fiber layer thickness (RNFLT) parameters measured with RTVue-OCT was
significantly (p<<0.001) smaller than that with either GDx method. RNFLT progression (% change/year) did
not differ significantly between the methods. Significantly (p<0.01) greater progression was found for RTVueOCT Rim Area, Inferior Rim Area, Rim Volume and Optic Nerve Head Volume in the perimetric glaucoma
group than in the control group. In contrast, no RNFLT and Ganglion Cell Complex (GCC) parameter
discriminated the progression between these groups. Superior and Nasal Rim Area slopes (p≤0.01) but no
RNFLT and GCC slopes discriminated the progressing glaucoma group and the control eyes.
Conclusions : Long-term RNFLT measurements are less variable with the RTVue-OCT than GDx-VCC and
GDx-ECC. Early structural progression of glaucoma may be better detected with RTVue-OCT rim area and
volume parameters than any RNFLT and RTVue-OCT GCC parameter.
Program: Ophthalmology
Supervisor: Holló Gábor
40
2012. április 12-13.
E/II-5
COLORECTAL CARCINOGENESIS FROM AN EPIGENETIC POINT OF
VIEW: WHAT CAN DNA METHYLATION ADD TO THE BETTER
MOLECULAR UNDERSTANDING OF ADENOMA-DYSPLASIACARCINOMA SEQUENCE?
Árpád V. Patai1, Orsolya Galamb1,2, Gábor Valcz1, Alexanda Kalmár1, Árpád Patai3,
Bálint Péterfia4, B Wichmann1, Katalin Leiszter1, Kinga Tóth1, Andrea Schöller1, István Fűri1,
Barbara Kinga Barták1, Zsófia Brigitta Nagy1, Sándor Spisák1,2, Ferenc Sipos1, Tibor Krenács4,
Béla Molnár1,2, Zsolt Tulassay1,2
1
2
3
4
2nd Department of Internal Medicine, Semmelweis University, Budapest
Molecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest
1st Department of Internal Medicine, Sopron County Elisabeth Hospital, Sopron
1st Department of Pathology and Experimental Cancer Research, Semmelweis University,
Budapest
Background: DNA methylation has been described to play an important role in colorectal carcinogenesis,
particularly in the proximal colon. In the distal colon DNA methylation has scarcely been studied.
Aims : Our primary aim was to study DNA methylation in multiple genes during adenoma-dysplasia-carcinoma
sequence (ADCS) in the left side of the colon and to identify a potential characteristic methylation pattern. Our
further aim was to correlate our DNA methylation profiles with whole-genome mRNA expression microarray
results and also to analyze potential markers on protein level.
Methods: For DNA methylation analysis 15 healthy colonic, 5 low-grade dysplasia (LGD), 5 high-grade
dysplasia (HGD), 10 CRC (UICC stage I-III), 4 normal adjacent (2 cm from macroscopic tumor margin) and 5
ulcerative colitis (UC) samples were endoscopically removed from the left side of the colon. DNA methylation
percentages of 96 genes were determined using Methyl-Profiler PCR array system based on methylation-sensitive
restriction enzyme digestion followed by fluorescence real-time PCR. For mRNA expression analysis 49 healthy
colonic, 25 LGD, 24 HGD and 24 CRC (UICC stage I-III) samples were applied for Affymetrix Whole-Genome
Expression Profile Microarray. In order to better characterize our samples, common genetic mutations (KRAS
codon 12/13 and BRAF V600E) were tested using RFLP and pyrosequencing. Immunohistochemistry (IHC) for
MLH1, MSH2 and MSH6 was performed to define microsatellite status. To examine the underlying mechanisms
IHC for DNA methyltransferases (DNMT) 1, 3a, 3b and SFRP1 was also performed.
Results: Analysis of 96 genes revealed hypermethylation of 8 genes in all 44 samples, additionally 34 genes were
hypermethylated in LGD, 50 genes in HGD and 30 genes in CRC. Overall mRNA expression levels were lowest
in precursor lesions, showing an inverse tendency to DNA methylation levels. Comparing methylation profiles
between CRC and normal adjacent showed that hypermethylation occurred only in cancer but not in the field. A
characteristic panel of 10 hypermethylated genes, including MAL, SFRP1, SLIT2 and ALDH1A3 (a novel
finding in CRC) significantly distinguished LGD, HGD and CRC from UC and normal tissue (p<0.05). SFRP1,
SLIT2 and MAL methylation levels inversely correlated with mRNA expression, and SFRP1 protein level
correlated with mRNA expression levels. DNMT3a correlated with overall methylation, showing strongest
expression in LGD and HGD. All samples were microsatellite stable (MSS), 2 samples (1 HGD, 1 CRC) showed
KRAS and 3 samples (2 LGD, 1HGD) BRAF mutation.
41
Conclusions : Sporadic, distal, MSS CRC has a characteristic methylation pattern. In our samples precancerous
lesions had more epigenetic and genetic alterations as compared to CRC and in this sense ADCS might be a nonsequential process on molecular biology level.
Program: Gastroenterology
Supervisor: Béla Molnár
42
2012. április 12-13.
E/II-6
INVESTIGATION OF TRANSPORTER INTERACTIONS OF
ANTIMALARIALS IN VITRO
Péter Szerémy1,2, Ildikó Makai1, Márton Jani1, Marton Lívia1, Szilvia Gedey1, Katalin Jakab1,
János Márki-Zay1,2, Péter Krajcsi1
1
2
Solvo Biotechnology
Department of Biochemistry, Faculty of Medicine, University of Szeged
Keywords: antimalarial, transporter interaction, ADME, in vitro assays, malaria, antimalarial, membrane transporter,
multidrug resistance
Options to control spread of malaria are increasingly limited due to emergence of parasites resistant to widely
used antimalarials, therefore, discovery of novel antimalarials appears crucial as ever. However, animal
experiments are too expensive and laborious for the pharmacokinetic characterization of large number of
compounds. The fate of administered drugs may largely depend on their interactions with transporter proteins,
which are present in all major pharmacologically relevant barriers. Furthermore, transporters are key
determinants of antimalarial drug resistance of plasmodiums as well. The aim of this study was to examine
whether the high-throughput (HTS) cell and membrane-based transporter assays can be applied to characterize
the transporter interactions of candidate antimalarials.
Reference antimalarials, such as artemisinin, chloroquine, mefloquine, quinine, etc, have been tested for their
interaction with the ABC-transporters MDR1, MRP1 and BCRP using the Solvo PredEasy ATPase kits and the
interaction with the SLC family members OCT1 and OCT2 uptake transporters in cell-based assay. Measured
IC50 and EC50 values were correlated with the clinical observations on the tested antimalarials.
In case of Amodiaquine, Hydroxychloroquine, Primaquine, Pyrimethamine, Proguanil, Artemisinin, Artesunate,
Atovaquone, Clindamycin, Halofantrine, our data are the first proof for transporter interaction of these clinically
important drugs. Artemisinin is a substrate for MDR1, chloroquine is inhibitor of the MDR1 and substrate for
the MRP1 and BCRP, mefloquine is substrate for the MDR1 but at higher concentrations is a not specific
inhibitor of all the transporters and quinine is substrate for the MDR1. These results corresponded exactly to the
clinical data on the antimalarials tested.
We conclude that the membrane- and cell-based HTS in vitro assays can be applied to facilitate the ADME
characterization of candidate antimalarials.
Doctoral School: Multidisciplinary Medicine, University of Szeged
Supervisor: Péter Krajcsi
43
E/II-7
ANALYZING THE RELIABILITY OF THE SPINAL INSTABILITY
NEOPLASTIC SCORE
National Center for Spinal Disorders, Budapest
Objective: The purpose of this study was to determine the interobserver and intraobserver reliability of the
Spinal Instability Neoplastic Score (SINS).
Summary of Background Data: Treatment indication for tumor related spinal instability lacks a valid and
reliable classification system. For aiding this paucity the Spine Oncology Study Group developed a novel scoring
system the SINS based on the experts’ experience. However, before the clinical validation of the SINS its
reliability must be determined.
Methods: Clinical information and imaging studies (X-Ray, CT and MRI) were compiled from 30 selected
patients with primary and metastatic spinal tumors. Three clinicians working in the field of spine care
independently estimated and scored the cases according to the SINS. The cases were classified as stable,
potentially unstable, and unstable conditions. Interobserver and intraobserver reliability of each SINS category
were assessed by applying the Fleiss and Cohen κ statistics.
Results: The κ statistics for interobserver reliability were 0.968, 0.945, 0.736, 0.506, 0.847 and 0.684 for the fields
of location, pain, bone quality, alignment, vertebral body collapse, and posterolateral involvement, respectively.
The κ statistics for intraobserver reliability were 0.975, 0.964, 0.793, 0.687, 0.770 and 0.737 for the same
respective fields. Intraclass correlation coefficients for inter- and intraobserver reliability of total SINS score were
0.851 (95% CI, 0.748 to 0.920) and 0.761 (95% CI, 0.624 to 0.881) respectively.
Conclusion: Results indicate moderate to near perfect interobserver reliability and substantial and near-perfect
intraobserver reliability for the six dimensions of the SINS. Before incorporating the classifications in the
everyday clinical practices, further studies are required to investigate the validity and prognostic power of the
scoring system.
Supervisor: Áron Lazáry
44
2012. április 12-13.
E/III
ORAL PRESENTATIONS
Chairman:
Prof. Dr. Károly Cseh
45
46
2012. április 12-13.
E/III-1
PH REGULATION DURING AMELOGENESIS – FUNCTIONAL
EVIDENCE OF BICARBONATE TRANSPORT IN HAT-7 AMELOBLAST
CELLS
Erzsébet Bori
Department of Oral Biology, Semmelweis University, Budapest
Tooth enamel formation (amelogenesis) can be divided into two major stages. In the secretory stage a protein
rich matrix is secreted by ameloblasts, then in the maturation stage proteins are degraded and hidroxyapatite
crystals expand rapidly generating a large number of protons. This local acidification could impair further crystal
growth without tight pH regulation. In recent years several proteins typical for bicarbonate transporting
epithelial cells were found to be expressed also in ameloblasts. However, there was no functional evidence for
bicarbonate transport in ameloblasts.
To investigate bicarbonate transport in vitro in the Hat-7 rat ameloblast cell line, we seeded the cells onto
polyester membranes to form polarized monolayers. We used 3 different media to further force tight junction
formation indicated by transepithelial resistance (TER). We measured intracellular pH and bicarbonte transport
by microfluorometry.
Hat-7 cells formed polarized epithelia on permeable supports. TER was highest in Hepatostim but DMEM-F12
containing 2.1 mM calcium and 10-8 M dexamethason also markedly elevated resistance compared to control
DMEM-F12 medium meaning the formation of functional tight epithelium. TERs measured on the fifth day
were 1185 ± 149, 502 ± 62 and 278 ± 13 Ωcm2, respectively. When cells were exposed to CO2/HCO3containing solution basolaterally, intracellular pH increased rapidly. This increase could be inhibited by 1 mM
acetazolamide or 500 μM H2DIDS (0.43 ± 0,06 vs. 0,14 ± 0,02 and 0,26 ± 0,01 pH unit/min, n=13, 8, 4,
respectively), which indicates intracellular HCO3- accumulation by cooperation of a membrane bound carbonic
anhydrase and a sodium-bicarbonate cotransporter.
In conclusion we developed a new previously unprecedented model for studying ameloblast electrolyte transport.
In this polarized monolayer we identified the basolateral transport mechanism responsible for intracellular pH
regulation and vectorial bicarbonate movement.
Doctoral School: Clinical medicine
Program: Dentistry
Supervisor: Gábor Varga
47
E/III-2
AMBULATORY ARTERIAL STIFFNESS INDEX IN CHILDREN AFTER
KIDNEY TRANSPLANTATION – CROSS SECTIONAL STUDY
Arianna Dégi, Andrea Kerti1, Attila J. Szabó1, Péter Sallay1, Éva Kis1, Orsolya Cseprekál1,2,
George S. Reusz1
1
2
1st Department of Pediatrics, Semmelweis University, Budapest
1st Department of Internal Medicine, Semmelweis University, Budapest
Cardiovascular (CV) disease is the leading cause of death in renal transplant (Rtx) patients. In paediatrics hard CV
end-points are lacking, thus subclinical organ damage as an intermediary end point should be assessed in this
population. Ambulatory arterial stiffness index (AASI) is known as surrogate CV marker in adults. Our aim was
to establish the factors influencing AASI and its possible relationship to central arterial elasticity.
54 Rtx children (15.5±3.5 years, 38 males) were investigated. AASI was calculated from the results of 24 hour
ambulatory blood pressure monitoring (ABPM) as 1-slope of the regression curve of diastolic on systolic blood
pressure (DBP, SBP) values. Central pulse wave velocity (PWV) was measured by applanation tonometry
(PulsePen). Body composition analysis (ECW/TBW – extracellular water/total body water) was done by Inbody
device. Measurement of anthropometric data (body mass index, BMI), laboratory values (B type natriuretic
peptide, BNP), and routine parameters) were taken, respectively. SD scores (SDS) were calculated.
AASI correlated significantly with BMI SDS, SBP SDS, pulse pressure (PP), ECW/TBW, DBP fall (DBPF) and
time on dialysis (r=0.39;0.36;0.49;0.49;-0.51;0.30 respectively p<0.03). By multiple regression analysis, PP (ß
0.32;SE 0.14;p=0.03), DBPF (ß -0.31;SE 0.12;p=0.02) and time on dialysis (ß 0.30;SE 0.12;p=0.01) proved to be
the main predictor of AASI. Children diagnosed as hypertensive (n=34) had higher AASI (0.5±0.1vs.0.3±0.1),
BNP
(61(0-340)vs.33(0-104)),
BMI
SDS
(0.50(-1.41–4.58)vs.0.06(-0.94–1.54)),
ECW/TBW
(37.8±1.3vs.36.9±1.0) and they spent longer time on dialysis (15(0-54)vs.4(0-74)) (p<0.03), but their PWV SDS
did not differ from normotensive patients (p=NS). PWV did not show a relation to AASI (r=-0.05; p=0.72).
AASI seems to characterize the actual volume and pressure dependent arterial rigidity rather than long term
morphological changes of large arteries – as reflected by PWV - in Rtx children. Thus, CV morbidity may be
reduced by adequate blood pressure lowering therapy, prevention of obesity and early kidney transplantation.
Program: Prevention of chronic diseases in childhood
Supervisor: Tivadar Tulassay
48
2012. április 12-13.
E/III-3
CHANGES IN PHOTOPIGMENT EXPRESSION AND
PHOTORECEPTOR MORPHOLOGY IN EARLY DIABETES
Anna Énzsöly1, Arnold Szabó2, Klaudia Szabó2, Ákos Lukáts2, János Németh1
1
2
Semmelweis University, Department of Ophthalmology, Budapest
Semmelweis University, Department of Human Morphology and Developmental Biology,
Budapest
Aims: Neurodegeneration as an early event of diabetic retinopathy preceding clinically detectable vascular
alterations is a widely proven issue today. Despite intensive studies of the inner retina, little is known about how
photoreceptors react to diabetic conditions. Loss of color vision and decreased contrast sensitivity have been
reported in humans, suggesting cone function impairment, but the morphological basis of the process is still
unknown. The aim of the present study was to investigate photoreceptor morphology and photopigment
expression in a rat model of diabetes.
Methods: In male Wistar rats aged 12 weeks, diabetes was induced with a single intraperitoneal injection of
streptozocin (n=5). 12 weeks after the induction rats were sacrificed; their eyes were enucleated and fixed.
Immunocytochemistry using opsin-specific antibodies were performed on wholemounted retinas and on
cryosections. The rate of apoptosis was evaluated using TUNEL reaction. Retinal pigment epithelial function and
morphology were analyzed at light- and electronmicroscopic level.
Results: Diabetes had no effect on the total number of cones expressing M- or S-opsins compared to control
retinas. TUNEL-positive cells were rarely detected in the outer nuclear layer in diabetes. However, we observed
alterations in the photopigment expression pattern, transport and outer segment morphology in the majority of
the cones. Electronmicroscopic and immunocytochemical data suggests that the pigment epithelium could also
be affected, which can account for damage of the photoreceptors.
Conclusions: To our knowledge this is the first report on anatomical assessment of diabetic neuropathology
finding notable alterations of the retinal cones and pigment epithelium. Our observations raise the question as to
color vision, contrast sensitivity and ERG abnormalities in diabetes could be associated with the morphological
alterations reported here.
Supervisor: János Németh
49
E/III-4
CLINICOPATHOLOGICAL FEATURES OF LUNG CANCER WITH
BRAIN METASTASES
Katalin Fábián
Department of Pulmonology, Semmelweis University, Budapest
Peritumoral brain edema is one of the most important factors influencing the quality of life in lung cancer
patients with brain metastasis.
We analyzed the clinicopathological data of 440 lung cancer patients with brain metastasis diagnosed either by
CT or MRI (240 men, 200 women, mean age: 59.64 years). The tumor was diagnosed cytologically in 113 cases
and histologically in 327 cases.
The histological distribution was the following: 193 adenocarcinomas (ADC), 107 small cell lung cancers (SCLC),
68 squamous cell cancers (SCC), 35 anaplastic carcinomas, 3 adenosquamous carcinomas, 2 atypical carcinoid
tumors, 6 large cell neuroendocrine carcinomas and 16 malignant tumors. At presentation 43.3% of brain
metastases were solitary and 56.3% were multiple. Central tumors were found in 61.2%, and peripheral in 38.8%.
In 255 cases the tumor was in the right lung. The upper lobe was involved in 237 cases. In ADC the proportion
of early brain metastasis (i.e. within 3 months after the diagnosis of primary tumor) was significantly higher than
in SCLC (p< 0,001). Brain metastasis was observed most frequently in ADCs localized to the upper lobes
(n=112), and among them the proportion of early metastasis was very high (n=70). Out of 440 patients 319 had
available information of the peritumoral edema. Edema was presented in 260 patients (169 patients had severe
(>10 mm), 91 patients had moderate edema (1-10 mm)). When compared SCLC either to ADC or to SCC,
incidence of severe peritumoral brain edema was significantly lower in SCLC (p< 0,001). The incidence of
perifocal edema influenced the overall survival. The patients without peritumoral edema had significantly longer
survival than the patients with edema (4.2 months to 7.6 months (p= 0.008)).
Our study indicates the aggressiveness of certain lung adenocarcinomas resulting in early hematogenous
metastasis and wider peritumoral brain edema. According to our results, especially in case of upper lobe
adenocarcinoma, the exclusion of intracranial metastasis by brain MRI is highly desirable before surgical resection
of lung cancer.
Program: Pulmonology
Supervisor: Judit Moldvay
50
2012. április 12-13.
E/III-5
POLYMORPHISM OF THE HSD11B1 GENE PROMOTER INFLUENCES
BONE MINERAL DENSITY
Karolina Feldman1, Ágnes Szappanos1, Zsófia Kövesdi1, Miklós Tóth1, István Likó2, Péter Lakatos3,
Károly Rácz1, Attila Patócs4,5
1
2
3
4
5
Richter Gedeon LTD, Budapest, Hungary
1st Department of Internal Medicine, Semmelweis University, Budapest
Department of Laboratory Medicine, Semmelweis University, Budapest
Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest
Objective: The 11β-hydroxysteroid dehydrogenase type 1 enzyme (HSD11B1) plays an important role in the
regulation of local glucocorticoid level in a tissue specific manner. In our present work we examined whether
SNPs in the promoter region of the HSD11B1 could influence bone metabolism.
Patients and methods: Online databases and bioinformatical analysis were used for identification and selection
of SNPs located in the 28 kb promoter of the HSD11B1 gene. Twelve SNPs (rs4393158, rs11576775,
rs17389016, rs760951, rs10082248, rs4844880, rs3753519, rs12086634, rs2236902, rs11807619, rs2884090 and
rs4844488) were selected and genotyped. The allele frequencies of rs4844880 located in the promoter region of
the HSD11B1 gene were determined in 183 healthy women and in 62 women with endogenous hypercortisolism
and in 140 women diagnosed with idiopathic osteoporosis using Taqman SNP assays on Real-Time PCR and
direct DNA sequencing. Functional characterization of the rs4844880 was performed by in vitro luciferase assay.
Results: The rs4844880 showed a significant association with higher bone mineral density and/or z-score at
lumbal spine and femoral neck in healthy women and in idiopathic osteoporotic women, but this association was
absent in patients with endogenous hypercortisolism. In vitro luciferase assay demonstrated that the polymorphic
rs4844880 allele more significantly inhibited the luciferase activity than the wild type allele.
Conclusions: The rs4844880 polymorphism in the promoter region of the HSD11B1 gene resulting in a reduced
expression of the enzyme may exert a beneficial effect on bone mineral content in women without
hypercortisolism. Hypercortisolism may suppress this favourable effect.
Supervisor: Attila Patócs
51
E/III-6
POSTCONDITIONING AS A PREVENTION METHOD AFTER LOWER
LIMB ISCHEMIA-REPERFUSION INJURY: REDUCING DAMAGES OF
THE LUNG
Dávid Garbaisz1, Zsolt Turóczi1, Olivér Rosero1, Gábor Lotz2, Zoltán Rakonczay3, László
Harsányi1, Attila Szijártó1
1
2
3
Experimental Surgery and Training Center, 1st Department of Surgery, Budapest
2nd Department of Pathology, Semmelweis University, Budapest
First Department of Medicine, University of Szeged, Szeged
Introduction: Operation on the infrarenal aorta or the major vessels of the lower limb could cause ischemic-
reperfusion (I/R) injury in local tissues and in remote organs (e.g. in the lung) subsequently. Locally released
metabolites, mediator molecules, oxygen-free radicals can cause – via activated polymorfonuclear leucocytes microvascular circulatory changes and damage in the lung, which may end in ARDS.
Objectives: Our aim was to reduce damages in the lung, after lower limb I/R with postconditioning.
Materials and methods: Male Wistar rats (n=90) underwent 180 minutes bilateral lower limb ischemia. Animals
were divided into three groups: Sham (n=10), Control (I/R, n=10), Postconditioned (PostC, n=10). In
postconditioned group, postconditioning was used after ischemia. Then groups were divided according to
reperfusion time: 3h, 24h and 72h groups.
After sampling, serum total antioxidant level, TNF-α and IL-6 levels, histological changes, Wet/Dry (W/D) ratio,
myeloperoxidase (MPO) activity and Hsp72 level were investigated.
Results: Histological changes were pronounced in the 4h and 24h I/R group, but PostC group has better results.
Total antioxidant level is significantly higher in the 4h PostC group than in the I/R group. TNF-α level is
significantly higher (p<0.01) in the 4h I/R group (44.9±8.6pg/ml) than in the PostC group (22.9±4.9 pg/ml). IL6 levels are increased both in the 4h I/R and PostC groups, but without significant difference
(251.0±51.1vs.317.4±37.7 pg/ml). Compared to the I/R group, lung MPO activity is increased to a lesser degree
in the PostC group in all time-points, but again without significant difference (18.23vs.15.18;
13.63vs.14.63;30.43vs.21.60). Hsp72 level in the 4h PostC group is higher than in the I/R group (1.3 vs. 1.0),
without significant difference. W/D ratio in PostC groups is significantly lower in all time-points than in I/R
groups (60.15%vs.63.20%;65.58%vs.68.28%;68.40%vs. 72.08%).
Conclusion: Postconditioning effect can reduce damages of the lung after infrarenal aortic and lower limb major
vascular occlusion.
Program: Clinical and experimental research in angiology
Supervisor: Attila Szíjártó
52
2012. április 12-13.
E/III-7
ANTI-INFLAMMATORY EFFECTS OF MOUSE MESENCHYMAL STEM
CELLS ON MICROGLIA
Beáta Hegyi
Stem Cell Biology Unit, National Blood Service, Budapest
The immunosuppressive and anti-inflammatory properties of mesenchymal stem or stromal cells (MSC) have
been demonstrated on a wide range of innate and adaptive immune cells.
It is well-known that neuroinflammation plays a crucial role in both pathogenic and regenerative processes of the
brain and is largely mediated by microglia and astrocytes, therefore we investigated the effects of mouse bone
marrow-derived MSCs on microglia.
We prepared primary mixed glia cell cultures and then selectively isolated primary microglia cells, co-cultured
with MSCs and investigated the phagocytic and antigen presenting capability of microglia and the attendant
production of pro- and anti-inflammatory factors in the presence or absence of bacterial endotoxin
lipopolysaccharide (LPS).
We found that MSCs in co-cultures and also in transwell cultures inhibited the activation of microglial cells and
changed the ratio of the secreted pro-inflammatory tumor necrosis factor-α (TNF-α) and anti-inflammatory IL10 in the supernatants. In addition the phagocytic activity of microglial cells were significantly increased by
MSCs. The MSCs also enhanced the antigen presenting capability of microglia and induced morphological
changes in these cells. Based on transwell experiments we hypothesize that the cross-talk between these cells is
mainly but not exclusively mediated by soluble factors, including prostaglandin E2 (PGE2).
These findings underline the theory that in the presence of MSCs microglia cells undergo alternative activation
and gain M2-like (anti-inflammatory) phenotype similarly to peritoneal macrophages. In summary, the observed
beneficial effects of MSCs may have relevance to treatment strategies for inflammatory diseases of the central
nervous system, apparently by alternative activation of microglia.
Program: Haematology
Supervisor: Ferenc Uher
53
E/III-8
SIGMA-1 RECEPTOR AGONIST TREATMENT IS PROTECTIVE
AGAINST RENAL ISCHEMIA/REPERFUSION INJURY
Ádám Hosszú 1,2, Nóra Fanni Bánki 1,2, Zsuzsa Antal 1 , Sándor Kőszegi 1,2, László Wagner 3, Ágnes
Prókai 1, Ádám Vannay 4, Veronika Müller 5, Attila Szabó 1, Andrea Fekete1,2
1
2
3
4
5
SE-MTA „Lendulet” Diabetes Research Group
Dep. of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University,
Department. of Transplantation and Surgery, Semmelweis University, Budapest
SE-MTA Nephrology Research Group
Introduction: In the ischemia/reperfusion (IR) injury of the heart activation of the Sigma-1 receptor (S1R)-Akt-
endothelial nitrogen monoxide synthase (eNOS) signal transduction pathway has a protective effect. However
there is no data concerning the link between renal IR injury leading to acute renal failure and S1R.
Aim: To study the effect of S1R agonist fluvoxamine (FLU) and antagonist NE-100 on postischemic survival,
renal structural and functional damage and the S1R-Akt-eNOS signaling pathway.
Methods: Uninephrectomized male Wistar rats were treated i.p. with FLU (20mg/bwkg; FLU), FLU and NE-
100 (1mg/bwkg; FN) and vehicle (VEH) 30 minutes before the 50 minute renal ischemia. Control (K) animals
were sham-operated (N=10/group). We observed postischemic survival and the deterioration of renal function
in the 24th hour of reperfusion. We studied the alteration of renal capillary diameter and structural damage in vivo
using muliphoton microscopy. The amount of renal S1R-Akt-eNOS proteins were determined by Western blot.
Results: FLU treatment improved postischemic survival. Deterioration of renal function and renal structural
damage was milder in FLU treated animals. This was characterized by the more preserved integrity of the brush
border and nuclei as well as less prominent hyaline accumulation. The reduced capillary diameter after IR was
increased by FLU treatment (K: 9,86 ± 1,23 µm; VEH: 8,29 ± 1,29 µm; FLU: 10,73 ± 0,67 µm). The increased
amount of renal S1R-Akt-eNOS proteins after IR was reduced by FLU treatment to the same level as in control
animals. NE-100 suspended all effects of FLU.
Discussion: The S1R agonist FLU treatment –used as an antidepressant chronically without notable side-effects
– could have a renoprotective effect in IR. We suspect the improvement of renal perfusion and the role of the
S1R-Akt-eNOS pathway behind this effect.
Supervisor: Andrea Fekete
54
2012. április 12-13.
E/III-9
NPHS2 P.V290M MUTATION IN LATE-ONSET STEROID-RESISTANT
NEPHROTIC SYNDROME
Background: Steroid-resistant nephrotic syndrome (SRNS) represents a common cause of ESRD both in adult-
and in childhood. In its genetic form, the most frequently mutated gene is NPHS2, which causes autosomal
recessive SRNS. Current guidelines propose the sequencing of all NPHS2 exons only in childhood-onset SRNS
and the screening of the p.R229Q variant in adolescents and adults.
Results: Here, in a cohort of 34 patients with SRNS, 9 of whom with NPHS2 mutations, we present 2 patients
carrying the p.V290M mutation with an extremely mild clinical course. The first, an 18-year-old man,
homozygous for p.V290M, was diagnosed with proteinuria through a school screening program at the age of 9.7
years. Renal histology –at the age of 15 years – showed FSGS. Till now, he has never developed edema, his
regularly checked albumin level dropped below 30g/l only once. The second patient, a 31-year-old woman –
compound heterozygous for p.V290M and p.R138Q – was also identified through a school screening program
with proteinuria at the age of 14 years. Her serum albumin level was first detected to drop below 30g/l at the age
of 24.3 years and she did not develop edema till the age of 27.5. She has currently a normal renal function. Thus,
if their proteinuria had not been identified by screening programs, these two patients would not have been
diagnosed with NPHS2 mutations by the currently proposed mutation-screening.
Conclusions: We propose that not only the p.R229Q variant, but also the p.V290M mutation should be
screened in Central and Eastern European patients with an onset of nephrotic syndrome below the age of 30
years.
55
E/III-10
THE ROLE OF THE SIGMA-1 RECEPTOR IN DIABETIC
NEPHROPATHY
Sándor Kőszegi1,2, Bánki Nóra Fanni1,2, Ádám Hosszú1,2, László Wagner3, Ágnes Prókai2, Ádám
Vannay4, Tivadar Tulassay 2,4, Andrea Fekete1,2
1
2
3
4
Department of Transplantation Surgery, Semmelweis University, Budapest,
Introduction: Depression is more frequent in diabetic patients and increases the occurrence of diabetic
complications such as diabetic nephropathy (DN). The renoprotective effect of elevated endothelial nitric oxide
synthase (eNOS) expression followed by vasodilatation is well known. Fluvoxamin (FLU), which is primarily
used as an antidepressant has been shown to activate the Sigma-1R-Akt-eNOS signaling pathway.
Aims: We investigated the effect of FLU treatment on the progression of DN and on the Sigma-1R –Akt –
eNOS pathway in an experimental model of DN.
Methods: Male, mature Wistar rats were rendered diabetic with streptozotocin (65mg/bwkg ip.) and treated 5
weeks later per os with FLU (20 mg/bwkg/die) for 2 weeks. Untreated diabetic (D) and healthy (C) animals served
as controls (n=8/group). We examined the deterioration of kidney function by measuring serum creatinin (Cre)
and urea (BUN) levels. Histological lesions were estimated by the extent of mesangial matrix expansion and
interstitial fibrosis. The amount of renal S1R-Akt-eNOS proteins was determined by Western blot.
Results: FLU treatment moderated the level of diabetes induced functional kidney lesions (Cre; BUN: p<0.05 vs.
D) and reduced the rate of glomerular mesangial matrix expansion and tubulointerstitial fibrosis ( p<0.001 FLU
vs. D). Renal Akt (p<0.001 vs. D) and eNOS (p<0.01 vs. D) protein levels were increased while the quantity of
Sigma-1R remained unchanged after FLU treatment.
Conclusion: The Sigma-1R agonist FLU, which is used chronically as an antidepressant in diabetes associated
depression without notable side-effects, could be renoprotective against DN. We suspect the role of the Sigma1R-Akt-eNOS pathway behind this effect.
56
2012. április 12-13.
E/III-11
ACTIVATION OF SMAD 2 AND 3 IN THE INTESTINAL MUCOSA OF
PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND
IN HT-29 CELL LINES
Kriszta Molnar1, Ádám Vannay2, Leonóra Balicza-Himer2, Apor Veres-Székely2, Dolóresz Szabó1,
Nóra Fanni Bánki1, András Arató1, Gábor Veres1
1
2
Research Group for Pediatrics and Nephrology, Semmelweis University and Hungarian
Academy of Sciences, Budapest
Objectives and Study: Tumor necrosis factor alpha (TNF-α) is crucial in the pathogenesis of inflammatory
bowel disease (IBD). In IBD intestinal fibrosis in IBD is a frequent issue despite the conservative therapy
including biological agents. The role of SMAD 2 and 3 (SMAD 2, -3) in fibrosis is emphasized in many organs,
but the effect of TNF-α on the activation of SMAD 2, -3 is not known. Our aim was to exam this signalling
pathways in IBD.
Materials and Methods: The localization of SMAD 2, -3, JNK, ERK signalling molecules were determined by
immunofluorescent staining. We tested the phosphorylation of SMAD 2 and 3 in the inflamed and non-inflamed
colonic mucosa of children with newly diagnosed IBD (n=15) compared to healthy controls (n=10) by Western
blot analysis. We investigated the expression of SMAD 2, -3 by FACS analysis in HT-29 cell lines treated with
TNF-α compared to controls.
Results: The immunofluorescent staining showed remarkable activation of SMAD 2, -3 in the enterocites in the
inflamed colonic mucosa of children with IBD. The protein level of phosphorylated SMAD 3 in the inflamed
mucosa of children with IBD was increased significantly compared to controls and the non-inflamed mucosa.
SMAD 2 phosphorylation was not significantly different in the groups studied. In the HT-29 cell lines there was
a significant increase in cells treated with TNF-α compared to controls.
Conclusion: TNF-α may play a role in the mucosal activation of SMAD3 in pediatric patients with IBD. SMAD
3 may have an impact in the intestinal fibrogenesis of IBD.
Supervisor: Gábor Veres
57
E/III-12
THE EFFECTS OF POSTCONDITIONING IN A LONG-TERM PERIOD
RAT LIVER ISCHEMIC-REPERFUSION EXPERIMENTAL MODEL
Rosero Olivér1, Ónody Péter1, Garbaisz Dávid1, Tamás Judith1, Kocsis Ibolya2, Lotz Gábor3,
Harsányi László1, Szijártó Attila1
1
2
3
1st Department of Surgery, Semmelweis University, Budapest
Central Laboratory, Semmelweis University, Budapest
Ischemia-reperfusion injury of liver is a clinically significant manifestation of several surgical interventions.
Ischemic-postconditioning (IPO) seems to be an appropriate and simple technique to ameliorate the ischemicreperfusion injury. The applicability of this procedure in longer ischemic periods of the liver still needs to be
assessed.
The aim of this study was to compare the protective effect of IPO applied after short and long-term ischemia in
a rat model of liver ischemia-reperfusion.
25 Wistar male rats were randomized into 5 groups (Figure1). Ischemia was performed by the application of a
clamp on the hepatic hilum, for 45 or 90 minutes according to the experimental group, followed by 6 hours
reperfusion. IPO was performed with 6 alternating cycles of 10sec reperfusion and 10sec reocclusion. Hepatic
microcirculation was monitored by laser Doppler flowmeter detecting the plateau maximum (PM) and the
reperfusion area (RA). Biliary epithelial cell damage was assessed by the constant measure of bile glucose and
GGT concentrations. Histological sections of liver and serum necroenzyme levels were also examined.
n=
Group A
Group B
Group C
Group D
Group E
5
5
5
5
5
45 min
90 min
6 hours
IPO
ischemia ischemia
reperfusion
+
+
+
+
+
+
+
+
+
+
Figure 1. – Experimental groups
GroupC had significantly (p<0.05) higher flow rates during reperfusion (PM:63% vs. 92%; RA: 57% vs. 99%)
and significantly lower serum ALT levels (870±56 U/l vs. 484±48U/l). Bile glucose and GGT levels decreased
significantly (p<0.05) with the use of postconditioning in the short term group. This protective effect was not
detected in the group exposed to long-term ischemia except for the histological sections where postconditioning
reduced the injury level (7.4± 2 vs. 9.4±1.6). No significant difference was observed between the results of the
groupD and E regarding the microcirculation (PM:18.3% vs. 27%; RT:12.6% vs. 16.7%) or biliary epithelial cell
damage.
The use of postconditioning immediately after the ischemia was able to ameliorate the hepatic injury caused by a
short ischemic period, but not by a long term ischemia.
Supervisor: Attila Szíjártó
58
2012. április 12-13.
E/III-13
POSITIONAL IDENTITY OF MURINE MESENCHYMAL STEM CELLS
RESIDENT IN DIFFERENT ORGANS IS DETERMINED IN THE
POSTSEGMENTATION MESODERM
Bernadett Sági
National Blood Service, Stem Cell Biology Unit, Budapest
Introduction: Multipotent mesenchymal progenitor cells, termed “mesenchymal stem or stromal cells (MSC)”,
have been demonstrated to reside in many organs.
Objectives: Although MSCs of distinct tissue origin have a large number of similarities and differences, it has
not been determined so far whether tissue-resident MSCs are the progenies of one ancestor cell lineage or the
results of parallel cell developmental events.
Methods: We compared the expression levels of 177 genes in murine MSCs derived from adult and juvenile
bone marrow and adult adipose tissue, as well as juvenile spleen, thymus, and aorta wall by quantitative real-time
polymerase chain reaction and the results were partially validated at protein level (flow cytometry,
immunohistochemistry, Western blot).
Results: All MSC lines uniformly expressed a large set of genes including well-known mesenchymal markers,
such as α-smooth muscle actin, collagen type I α-chain, GATA6, Mohawk, and vimentin. In contrast,
pluripotency genes and the early mesodermal marker T-gene were not expressed. On the other hand, different
MSC lines consistently expressed distinct patterns of Hox genes determining the positional identity of a given cell
population. Moreover, MSCs of different origin expressed a few other transcription factors also reflecting their
topological identity and so the body segment or organ to which they normally contributed in vivo: (1) thymusderived cells specifically expressed Tbx5 and Pitx2; (2) spleen-derived MSCs were characterized with Tlx1 and
Nkx2.5; (3) Pitx1 designated femoral bone marrow cells and (4) En2 appeared in aorta wall-derived MSCs. Thus,
MSCs exhibited topographic identity and memory even after long-term cultivation in vitro.
Conclusion: On the basis of these results, we suggest that postnatal MSCs isolated from different anatomical
sites descend from precursor cells developing in the postsegmentation mesoderm.
Supervisor: Ferenc Uher
59
E/III-14
BIOMARKERS OF BONE FORMATION AND GUT PERMEABILITY IN
LONG-TERM INFLIXIMAB THERAPY IN PEDIATRIC PATIENTS WITH
CROHN'S DISEASE
Introduction: Treatment with infliximab (IFX) may improve growth and disturbed bone metabolism in pediatric
patients with Crohn disease (CD), but the characteristics of bone formation, resorption factors and gut
permeability under IFX treatment are not well known.
Aim: To analyze the effect of IFX treatment on bone formation, resorption and gut permeability under longterm IFX treatment. Furthermore, CRP, vitamin D level, disease activity index (Pediatric Crohn's Disease
Activity Index, PCDAI), and dual energy x-ray absorptiometry (DEXA) after 54 weeks of IFX therapy were
analyzed also.
Methods: Thirty-three subjects (mean age 14.9 years) with moderate to severe CD received IFX induction (5
mg/kg/dose) at weeks 0, 2, and 6. Maintenance therapy was given all patients every 8 weeks. Serum
osteocalcin/OC, beta-crosslaps/bCL, bone-specific alkaline phosphatase/bALP, and vitamin D were collected at
baseline, at weeks 6, 30 and 54 weeks, in addition CRP and PCDAI were determined. DEXA z-scores were
assessed at baseline and week 54. Gut permeability was analyzed by lactulose/mannitol test at baseline and at
week 10.
Results: Serum levels of bone formation OC increased, meanwhile PCDAI decreased significantly due to IFX
induction treatment with respect to baseline levels (p<0.0001). bCL and bALP increased significantly until 30
weeks (p<0.0001) with respect to baseline, however they slightly decreased at weeks 54. Significant change was
observed in CRP (p<0.0001) and vitamin D (p=0.0009) until 6 weeks. DEXA z-score of the lumbar spine
showed improvement of bone density. The lactulose/mannitol ratio has not been changed at week 10 with
respect to baseline (mean score at baseline: 0.064; at week 10: 0.062; p=0.8464) depicting unchanged gut
permeability.
Conclusions: Due to IFX treatment clinical condition of patients and bone metabolism improved indicating
beneficial impact on bone formation. There was no effect of IFX treatment on gut permeability suggesting other
mechanism of IFX treatment on bone formation.
60
2012. április 12-13.
E/III-15
9-CIS-RETINOIC ACID-INDUCED GENE EXPRESSION ALTERATIONS
IN AN ADRENOCORTICAL CELL LINE
Diana Rita Szabó1, Peter M. Szabó1, Adrienn Zsippai1, Katalin Éder2, Attila Patócs3, András Falus2,
Károly Rácz1, Peter Igaz1
1
2
3
2nd Department of Medicine, Semmelweis University, Budapest
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest
Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis
University, Budapest
Introduction: Adrenocortical carcinoma is a rare tumor with poor prognosis. In our previous meta-analysis of
adrenocortical tumor genomics data, retinoic acid signaling was established as a major, novel pathogenic pathway,
and adrenocortical cancer was associated with reduced retinoic acid production and signaling. Our aim was to
examine 9-cis-retinoic acid-induced mRNA expression changes in the NCI-H295R adrenocortical cancer cell line.
Materials and methods: Various concentrations of 9-cis-retinoic acid in different treatment periods (24-72 h)
have been tested on cell viability and for hormone measurements to select the optimal treatment concentrations.
Total RNA has been subjected to Agilent 4x44 K microarray platforms. Statistical and pathway analysis of
microarray results were performed by Genespring software and Ingenuity Pathway Analysis. Microarray results
were validated by qRT-PCR.
Results: 9-cis-retinoic acid decreased cell viability and cortisol secretion. We have selected the 24 hour treatment
time and three 9-cis-retinoic acid concentrations (2.5x10-5M, 5x10-5M, 7.5x10-5M). By the statistical analysis of
microarray data, 832, 2953 and 2997 significant gene expression changes have been found between controls and
the three concentrations tested, respectively. Pathway analysis revealed four major pathways in 9-cis-retinoic acid
treated cells that strongly correlated with the data of previous adrenocortical carcinoma microarray studies: i. cell
cycle damage, ii. retinoic acid signaling, iii. changes of hormone secretion and iv. changes of immune response.
Conclusion: We have demonstrated that 9-cis-retinoic acid decreased cell proliferation and hormone secretion in
the NCI-H295R cell line and we have identified the most prominent gene expression changes and pathways. Our
results raise the possible utility of 9-cis-retinoic acid in the treatment of adrenocortical carcinoma.
Supervisor: Péter Igaz
61
E/III-16
DIFFERENT ADJUVANT ANTIOXIDANT TREATMENTS IN FATTY
LIVER
Viktor Hegedüs 1,6, Dénes Kleiner1, Kálmán Ditrói1, József Prokisch2, Hedvig Fébel3, Éva Sárdi4,
Gábor Lotz5, Attila Szijártó6, Anna Blázovics1
1
2
3
4
5
6
Department of Phramacognosy, Semmelweis University, Budapest
Department of Agricultural Center, Debrecen University, Debrecen
Research Institute for Animal Breeding and Nutrition, Hungarian Academy of Science, Budapest
Corvinus University, Budapest
1st Department of Surgery, Semmelweis Univerity, Budapest
Introduction : Fatty liver can be considered low-grade systemic inflammation. The past several years have shown
a growing interest for adjuvant antiinfalmmatory therapy in fatty liver. Three different antioxidant agent were
used: table beet (useful for methydonating, antioxidant flavonid content), nanoselenium (cofactor of antioxidant
enzymes) and cannabidiol (potent antioxidant).
Aims : Our aims were to investigate the effect of table beet, nanoselenium and cannabidiol in alimentary induced
fatty liver to evaluate its moderation of redox-homeostasis, transmethylating abilty and content of fatty acids.
Material and methods : Male Wistar rats (200-250 bwg) were fed with or without high-fat diet for 10 days. High
fat diet contained 2% cholesterol, 0.5% cholic acid, 20% sunflower oil mixed in their chow. After 3-day fatty liver
induction a 7-day bioactive agent treatments were carried out as table beet in 0,1g/bwkg dose, nanoselenium in
2,33µg/bwkg dose and cannabidiol in 20mg/bwkg dose via gastric tube. Routine laboratory and global
antioxidant parameters (induced chemiluminescence intensity, H-donating ability, free SH-group concentration
and reducing power), transmethylating abilty, fatty acid analysis as well as histopathological examinations were
carried out.
Results : Both table beet, nanoselen, and cannabidiol decreased free radical reactions both in liver homogenates
in different rates and increased the antioxidant parameters (H-donating and free SH-group) in fatty liver.
Transmethylating ability was highest in the table beet treated group in fatty liver. Histopathological examinations
showed moderately beneficial alterations in the treated animals already during 7 day-treatment.
Conclusion : On the basis of our results table beet, nanoselen and cannabidiol are potent liver protecting agent in
different ways in fatty liver.
Supported by ETT 002/02.
Program: Oxidative stress and immunological reaction in liver diseases
Supervisor: Anna Blázovics
62
2012. április 12-13.
E/IV
ORAL PRESENTATIONS
Chairman:
Dr. Péter Hamar
63
64
2012. április 12-13.
E/IV-1
THE FIRST CENTRAL-EUROPEAN CARDIOVASCULAR PREVENTION
STUDY - BUDAKALASZ HEALTH EXAMINATION SURVEY
Zsolt Bagyura, Zsolt Szelid, Pál Soós, Loretta Kiss, Béla Merkely
Background: Even though the role of cardiovascular prevention increased enormously in Europe in recent
years, there still remain large differences between countries. This is especially so in the emerging economies of
Central and Eastern Europe. Large population national cohort studies are necessary to establish comparable data
and build basis for adequate health-economical decisions.
Aim: The Budakalász Cardiovascular Health Examination Survey (BCHES) is a cardiovascular examination
survey designed to serve as a demonstration project for data collection on the prevalence of cardiovascular
diseases and their risk factors at the country level of a Central European country, Hungary.
Methods: A large cardiovascular screening programme was started involving the adult population (>20y) of a
Central-Hungarian town, Budakalász. The complete adult population (8.000 inhabitants) of the selected town is
targeted in our voluntary programme. Protocol includes health questionaire, non-invasive tests (cardiac- and
carotid ultrasound, resting blood pressure and ankle-brachial index) and venous blood biobanking (serum, plasma
and DNA), using coded samples linked to a clinical database. A web based database and its related biobank had
been developed for prospective collection of tissue specimen. Low-dose cardiac CT for coronary calcium and
cardiac fat determination is also performed in certain age groups (>35y in males and >40y in females).
Results: Six houndred and five inhabitants have been screened until mid January 2012 (mean age: 48,9y).
Increased body mass index (over 25 kg/m2) has been detected in 446 inhabitants (74%), in 268 (44%) enhanced
systoloc blood pressure, in 278 people (45%) elevated HgbA1c (40 mmol/l) has been detected and pathologic
LDL cholesterol level has been verified in 299 inhabitants (49%). Elevated high-sensitivity CRP (2-10 mg/L) was
measured in 235 people (39%). Preserved left ventricular ejection fraction with elevated NT-proBNP level has
been measured in 87 inhabitants (14%). Average cardiovascular mortality risk is 20,7%. Our pilot results are
comparable to other large national cohorts.
Discussion: Our goal is to complete the survey on the total adult population of the selected town and to
continuously report longitudinal follow-up studies to analyze associations between cardiovascular risk factors,
morbitity and mortality in a primary prevention Hungarian cohort.
65
E/IV-2
EFFECTS OF THE BENZODIAZEPINE DERIVATIVE, 5-BDBD ON THE
P2X4 PURINERGIC RECEPTOR CHANNEL
Budapest
Background: The lack of specific inhibitors hampers investigations on ATP-gated P2X4 purinergic receptor
channels. These channels function as non-selective cation channels allowing Ca2+ and Na+ influx into the cells.
The benzodiazepine derivative, 5-BDBD has been recently described as a potent inhibitor of the P2X4 receptors.
However, no data are available on its effects in the presence of ivermectin, an allosteric modulator of the P2X4
receptor channels.
Aims: We intended to compare the inhibitory effects of 5-BDBD and that of TNP-ATP, a non-specific inhibitor
of the P2X4 receptors. We also investigated the inhibitory effects of 5-BDBD in the presence of ivermectin.
Methods: Complementary DNA encoding human P2X4 receptors were transiently transfected into HEK-293
cells. Western-blot analysis was performed to verify the presence of P2X4 protein. To measure P2X4 channel
activity, we used the patch clamp technique in whole cell configuration. We also detected changes in cytosolic
Ca2+ concentration using Fluo-3, a Ca2+-sensitive fluorescent dye.
Results: ATP (1 μM) induced inward cation current in the HEK-293 cells expressing P2X4 receptor channels.
The ATP-evoked current was potentiated by ivermectin (3-10 μM) confirming the functional presence of P2X4
receptor channels. 5-BDBD inhibited the current amplitude in a dose-dependent manner (IC50=1,3 μM). TNPATP proved to be less effective (IC50=3,8 μM). ATP (0,5 μM) induced sustained calcium signal only in cells
expressing P2X4 receptor channels. The Ca2+ plateau was further elevated in the presence of ivermectin (3-10
μM) but was completely abolished by removing extracellular Ca2+. Both 5-BDBD (0,5 μM-20 μM) and TNP-ATP
(0,5 μM-50 μM) inhibited this ATP-induced Ca2+ plateau in a dose-dependent manner. Importantly, 5-BDBD
maintained its inhibitory effects in cells stimulated with the combination of ATP and ivermectin.
Conclusion: 5-BDBD maintains its inhibitory effect in the presence of ivermectin suggesting the usefulness of
this inhibitor.
Supervisor: Ákos Zsembery
66
2012. április 12-13.
E/IV-3
H2S PRECONDITIONING OF THERAPEUTICALLY USED STEM CELLS
INCREASES THEIR SURVIVAL AND EFFICACY IN AN IN VITRO
MODEL OF CELL-BASED THERAPY IN MYOCARDIAL INFARCT
Budapest
Introduction: The potential of cell-based therapies in diseases involving ischemia-reperfusion is greatly
hampered by the excessive loss of the administered cells in the harsh, oxidative environment. In previous studies
H2S had a protective effect during ischemia-reperfusion, therefore we investigated if pretreatment with a H2S
donor can improve the efficacy of the therapeutic cells in an in vitro model of cell-based therapy in ischemiareperfusion.
Materials and Methods: Ischemic conditions were simulated by oxygen and glucose deprivation for 155 min
using H9c2 rat cardiomyoblasts. After 30 minutes of reoxygenization postischemic cells received fluorescently
labeled human adipose tissue derived stem cells. In the three experimental groups the adipose derived stem cells
were untreated (ASC-0) or 3 µM NaHS treated (ASC-3) or 30 µM NaHS treated (ASC-30). After 24 hours we
measured the survival of the therapeutic stem cells as well as the survival of the postischemic cardiomyoblasts
with flow cytometry using fluorescent viability stains.
Results: In both cases NaHS treatment decreased the ratio of dead adipose derived stem cells versus the control,
but the 30 µM concentration to a lesser degree (ASC-0: 6.7± 0.7%; ASC-3: 3.9±0.5%; ASC-30: 4.4±0.6%;
mean±SEM; p<0.05 in both cases; n=6). The ratio of dead postischemic cardiomyocytes decreased in the ASC-3
group but there was no significant change in the ASC-30 group (ASC-0: 10.7± 1%; ASC-3: 7.0±1.1%; ASC-30:
8.3±0.9%; mean±SEM; ASC-0 vs. ASC-3, p<0.05, n=6).
Conclusions: The H2S treatment decreases the cell death of the therapeutic cells in the harsh postischemic
microenvironment which leads to improved effectiveness, however at the higher concentration level this
beneficial effect is decreased.
References:
Dongó et al. The cardioprotective potential of hydrogen sulfide in myocardial ischemia/reperfusion injury. Acta Phys Hung 2011
98:369-381.
Kiss et al. Hydrogen sulfide decreases adenosine triphosphate levels in aortic rings and leads to vasorelaxation via metabolic
inhibition. Life Sci 2008, 83:589-94.
Supervisor: Levente Kiss
67
E/IV-4
BILAYER EDGES CATALYZE LIPOSOME BINDING, MOVEMENT AND
RUPTURE ON SOLID SURFACES
Tamás Bozó
Department of Biophysics and Radiation Biology, Semmelweis University, Budapest
Liposomes usually flatten and rupture on solid surfaces to form patches or supported planar bilayers (SPBs) with
possible coexistence of distorted vesicles. Since SPBs as interfaces mimicking biological membranes can be used
for various applications (coating of artificial articular surfaces, producing biosensor arrays, etc.) the mechanism of
their formation from vesicles has been intensively studied but it is still far from being fully understood.
Aims: Recently we began investigating liposomes on a single-particle basis, whereby the individual behavior of
vesicles may be followed. Atomic Force Microscopy (AFM) measurements permitted the observation of rupture
of individual liposomes and spreading of lipid patches. Our goal was to obtain better understanding of liposome
dynamics on solid surfaces.
Results: Divalent cations were found to control the morphology of mica-adsorbed vesicles. Ca2+ and Mg2+ above
10 mM concentration prevented vesicles from being flattened or ruptured. Direct observation of individual
vesicles showed that their binding affinity was higher to the bilayer edges than to the substrate and they
practically did not bind to the surface of patches. Not only did the results highlight the importance of active
bilayer edges in liposome burst, but they also revealed the ice-floe-like flowing behavior of SPBs, that forces
unruptured vesicles to move, detach from, or rupture on the surface.
Fig. 1. – 2x2 μm AFM images of vesicles on mica.
a. Small unilamellar vesicles (SUVs)
b. Supported planar bilayer (SPB) patches formed from SUVs
Program: Biological effects of ionizing and non-ionizing radiations
Supervisor: Miklós Kellermayer
68
2012. április 12-13.
E/IV-5
CORONARY INTERVENTION LEADS TO COMPLEMENT ACTIVATION
THROUGH THE ALTERNATIVE PATHWAY
Zsófia Horváth1, Dorottya Csuka2, Katarina Vargova1,3, Andrea Kovács1, Andrea Ágnes Molnár1,3,
Leé Sarolta1,Lilian Varga2, Róbert Gábor Kiss1,3, István Préda1,3, George Füst2
1
2
3
3rd Department of Internal Medicine, Semmelweis University, Budapest
Military Hospital, Department of Cardiology, Budapest
Background: Complement activation might play an important role in the pathophysiology of coronary artery
disease (CAD). However, the plasma level of complement activation products in stable angina (SA), or the effects
of percutaneous coronary intervention (PCI) on complement system were not elucidated. Aim: Examining SA
patients we determined the early complement activation during PCI. Than, we evaluate the predictive value of
complement activation products in stable form of CAD.
Patients and Methods: We recruited 76 stable angina patients undergoing diagnostic coronarography. We
formed three groups according to the coronarography results: stable angina with PCI (PCI, n= 24, 31.6%),
positive coronarography without intervention (PC, n= 27, 35.5 %), and negative coronarography (NC, n= 25,
32.9 %). Healthy volunteers (HC, n=113), NC and PC groups served as controls. Blood samples were taken on
admission, 6 and 24 hours after coronarography/PCI. Complement activation products -C1rC1sC1inh (classical
pathway), the C3bBbP (alternative pathway), and the SC5b-9 (MAC) - were measured by ELISA.
Results : In PCI and PC group, the C1rC1sC1inh baseline levels were significantly higher compared to HC (PCI
vs. healthy: p<0.001 and PC vs. healthy: p<0.001). The baseline concentration of SC5b-9 was significantly higher
in NC group compared to HC (NC vs. healthy: p<0.001). Six hours after PCI/ coronarography the C3bBbP
plasma level increased in all patient groups (PCI: p<0.01, NC: p<0.01, PC: p<0.01), than a significant decrease
was observed at 24 hours (PCI: p<0.0001, NC: p< 0.0001, PC: p< 0.05). After multiple logistic regression
analysis the high C1rC1sC1inh baseline level proved to be an independent biomarker of the CVD (p<0.0001,
OR: 10.0, 95% CI: 4.4-22.8).
Conclusion: Both elective PCI and diagnostic coronarography lead to early complement activation trough the
alternative pathway. According to our results, the C1rC1sC1inhibitor might serve as an independent biomarker
of CAD.
Program: Clinical and experimental cardiology/ Atherosclerosis
Supervisor: Róbert Gábor Kiss
69
E/IV-6
NANOMECHANICS OF DESMIN FILAMENTS EXPLORED WITH
OPTICAL TWEEZERS
Balázs Kiss1, Pasquale Bianco2
1
Laboratorio di Fisiologia, DBAG, Dipartimento di Fisica, Polo Scientifico, Sesto Fiorentino
2
Desmin forms the intermediate filament system of muscle cells where it plays important role in maintaining
mechanical integrity and elasticity. Although the importance of intermediate-filament elasticity in cellular
mechanics is being increasingly recognized, the molecular basis of desmin's elasticity is not fully understood. In
the present work we explored the mechanical properties of purified and reconstituted desmin filaments by using
optical tweezers.
Desmin, purified from chicken gizzard, was polymerized by the addition of MgCl2. Desmin assembly was
monitored by using atomic force microscopy. For mechanical manipulation, desmin filaments were captured
between two anti-desmin-coated latex beads, one of which was positioned in a force-measuring optical trap and
the other one held and manipulated with a moveable micropipette. The micropipette was moved either with a
constant velocity or desmin filaments were stretched with a constant force. Alternatively, desmin was covalently
crosslinked on the surface of latex beads enabling high force stretch measurements up to 200 pN. By moving the
micropipette away from the trap, typically a few-micrometer section of the captured desmin filament was
stretched. Non-linear portions of the elastic curves were fitted with the wormlike-chain entropic polymer model,
yielding an average 0.5 nm apparent persistence length (measure of bending rigidity). Considering that the
persistence length is similar to that of unfolded protein molecules, is conceivable that the mechanical response of
the unfolded desmin was observed. In the force versus extension curves transitions appeared at 10 pN, which
extended the filament by ~14.5 nm. This contour length increment might correspond to sliding between
staggered dimers. Under constant force desmin filaments gradually extend and display length fluctuations. These
length fluctuations most probably arise due to axial rearrangement of desmin dimers.
Acknowledgement: This study was supported by TAMOP-4.2.1.B-09/1/KMR-2010-0001
70
2012. április 12-13.
E/IV-7
REVERSIBLE LOW-FORCE-DRIVEN STRUCTURAL TRANSITIONS IN
SKELETAL MUSCLE TITIN REVEALED BY FORCE-CLAMP OPTICAL
TWEEZERS
The giant protein titin is a filamentous protein that spans the half sarcomere and forms a third filament system in
the sarcomere. Titin is the main contributor to the passive force development of skeletal and cardiac muscle.
Based on the current model of titin’s sarcomeric extension the molecules I band region is involved in stretch
elongation. This region consists of serially linked immunoglobulin domains and a unique sequence, the
polyelectrolyte-chain PEVK domain. The stretch elongation of sarcomeric titin involves the straightening of
these regions, however the unfolding of Ig domains under physiological conditions is strongly debated.
Here we demonstrate discrete structural transition during the stretch of individual titin molecules in the
physiological force regime by applying high resolution optical tweezers experiments. Upon stretch, significant
over-extensions occur in the 10-30 pN range that increases the molecules end-end length. In force-clamp
experiments the molecule extends via discrete steps, that show good correspondence on previous results with
recombinant homopolymers.
Our findings support the possibility of in situ titin domain unfolding under physiological conditions. Such titin
based structural transitions may play a role in sarcomeric stress adaptation.
71
E/IV-8
DETAILED HEMODYNAMIC CHARACTERIZATION OF ATHLETE’S
HEART USING LEFT VENTRICULAR PRESSURE-VOLUME ANALYSIS
IN A RAT MODEL
Attila Oláh, Árpád Lux, Ede Birtalan, László Hidi, Balázs Németh, Béla Merkely, Tamás Radovits
Background: The development of professional sport and sudden cardiac death cases among athletes aroused
emerging interest in sports cardiology. Several research groups investigated exercise training induced left
ventricular (LV) hypertrophy in animal models, however only sporadic data exists about detailed hemodynamic
measurements. We aimed to establish and validate the rat model of athlete’s heart and provide a detailed
functional characterization using the modern sophisticated method of pressure-volume (PV) analysis.
Methods: LV hypertrophy was induced by swimming training (200min/d for 12 weeks). Sedentary rats were
placed in the swimming apparatus for 5min/d. After completion of the swimming portocol we performed
echocardiographic measurements and LV PV analysis using a microtip pressure-conductance catheter to
investigate the morphology and function of the LV, respectively.
Results: Echocardiographic examinations showed LV concentric hypertrophy according to the wall-thickness
values (LV mass index:2.41±0.08 vs. 2.03±0.08g/kgBW, p<0.05), which was confirmed by post-mortem
measured heart weight and histological morphometry.
Invasive hemodynamic measurements showed unchanged heart rate, arterial pressure and LV end-diastolic
volume along with decreased end-systolic volume, increased stroke volume (175±8 vs. 145±8µl) and ejection
fraction (73±1 vs. 64±2%) in trained rats compared to sedentary controls. The PV loop-derived sensitive, loadindependent contractility indexes were found to be significantly increased (preload recruitable stroke work: 77±7
vs. 54±5mmHg). We observed increased LV stroke work (15±1 vs. 11±1mmHg*ml) and maximal power (92±9
vs. 60±6mW) in athlete’s heart. Despite the significant hypertrophy, the LV stiffness was not increased, while
there was an improvement in active relaxation (Tau: 9.6±0.3 vs. 10.9±0.3ms).
Conclusion: According to our results, we established a rat model of physiologic LV hypertrophy. It is the first
study, which provides a detailed characterization of functional changes and hemodynamic relations in athlete’s
heart.
Supervisors: Tamás Radovits, László Gellér
72
2012. április 12-13.
E/IV-9
MEASURMENT OF PLATELET ADHESION USING IMPEDANCE
BASED TECHNIQUE
Lívia Polgár
Department of Genetics, Cell- and Immunobiology, Chemotaxis Research Group, Semmelweis
Purpose: Optimal antithrombotic therapy is essential in the treatment of most cardiovascular patients. The exact
knowledge of platelet function is required for balancing a safe therapy. The measurement of platelet function has
been researched for decades, different methods developed have been developed with varying applicability.
Impedimetry is an in vitro technique for the measurement of cell adhesion, viability, proliferation and cytotoxicity
with growing popularity for its sensitivity. The objective of our work was to examine platelet adhesion using this
impedance based technique.
Method: This technique applies golden electrodes as adhesion surface. The adhering platelets – behaving as
insulators – change the measured electric impedance. This change is in direct correlation with the number of
adhering platelets and the level of adhesion. Pooled human platelet samples were used. Platelet adhesion was
measured continuously on different platelet densities and in the presence of different drugs (heparin and
derivatives, antiplatelets, activators). Adhesion activity was quantified using the slope of the rising curve.
Results: Impedimetry monitored platelet adhesion activity with high sensitivity. The difference in platelet
densitiy was mirrored by the difference in the measured adhesion activity. The dynamics of platelet adhesion
showed two phases (short and long term). The effect of the measured drugs was more characteristic in short
term. Heparin and the low-molecular weight heparines had mostly positive effect on platelet adhesion with the
exception of bemiparin. The aggregation inhibitor aspirin had no effect on the measured electric impedance – i.e.
platelet adhesion activity.
Conclusion: Impedimetry is a useful method for the characterization and measurement of platelet adhesion. The
effect of the clinically used drugs on platelet adhesion could be demonstrated. These results show that – by
providing a real-time description of platelet adhesion activity – impedimetry could be a useful method for
monitoring the effectiveness of antithrombotic therapies.
Program: Phisiology and clinics of the heart and coronary diseases
Supervisor: László Kőhidai
73
E/IV-10
NANOMECHANICAL MANIPULATION OF MASON-PFIZER MONKEY
RETROVIRAL RNA FRAGMENT WITH OPTICAL TWEEZERS
Melinda Simon1, Zsolt Mártonfalvi1, Pasquale Bianco1, Beáta Vértessy2, Miklós Kellermayer1
1
2
Institute of Enzymology, Budapest
Mason-Pfizer monkey virus (MPMV) is an excellent model for the analysis of retrovirus assembly and
maturation. However, neither the structure of the viral RNA, nor its modulation by capsid-protein binding are
exactly known. To explore the structure of the MPMV genome, here we manipulated individual molecules of its
packaging signal sequence with optical tweezers.
The 207-base-long segment of MPMV RNA corresponding to the packaging signal, extended on each side with
1200-base-long indifferent gene segments for use as molecular handles, was cloned into a pET22b vector. RNA
was synthesized in an in vitro transcription system. RNA/DNA handles were obtained by hybridization in a PCR
with complementary DNA initiated with primers labeled with either digoxigenin or biotin. The complex was
manipulated in repetitive stretch and relaxation cycles across a force range of 0-80 pN. During stretch, the force
increases monotonically with extension, and above 15 pN unfolding transitions are typically observed. The length
gain (∼120 nm) associated with the unfolding is in a good agreement with the theorical contour length of the
ssRNA segment (207 bases). Reverse transitions (at force below 10 pN) were observed during mechanical
relaxation, indicating that refolding against force proceeds in a quasi-equilibrium process.
74
2012. április 12-13.
E/IV-11
THE EFFECT OF THE OBSTRUCTIVE SLEEP APNEA ON THE NIGHTTIME GLUCOSE VARIABILITY IN PATIENTS WITH METABOLIC
SYNDROME
Orsolya A. Veber1, Andrea Dunai1, Rezso Zoller1, Zsofia Lendvai1, Anett V. Lindner1,
Istvan Mucsi12
1
2
Institute of Behavioural Sciences, Semmelweis University, Budapest
Obstructive sleep apnea (OSA) is often accompanied by metabolic syndrome (MetSyn). OSA increases the
sympathetic activity, through which it can also influence the carbohydrate metabolism.
Aims: To analyse the connection between the apnea severity and the night-time glucose variability, using the
continuous glucose monitoring system (CGMS).
Participants: Thirty-eight patients with the MetSyn (according to the new International Diabetes Federation
criteria) from the diabetes outpatient clinic of the 1st Department of Internal Medicine at Semmelweis University,
Budapest. 26 male; age: 60±14 (mean±SD) yrs; diabetes duration: 10.6±10.6 év; HbA1c: 7.1±1.2%; Body Mass
Index : 33±7 kg/m2.
Methods: All patients underwent overnight polysomnography. OSA severity was defined with the apneahypopnoea index (AHI). Respiratory disturbance index (RDI) was also measured. Simultaneously, during the
polysomnography (8 hours), intersticial glucose values were assessed using CGMS.
Results: Eleven patients had severe, nine moderate and eight mild OSA, while 10 patients had an AHI of less
than 5. Comparing the normal-mild with the moderate-severe OSA group: in the moderate-severe OSA group
the daily insulin dose was higher (54±57 vs. 19±31 IU; p=0.035) and the average of the CGMS glucose values
was lower (6.3±1.6 vs. 5.6±0.8; p=0.038). In the more severe OSA group the standard deviation (SD) of the
CGMS data (0.51±0.2 vs. 0.79±0.5; p=0.032), the difference between the maximum and minimum glucose values
(amplitude) (2.1±0.7 vs. 3.2±1.7; p=0.028) were higher. We found a moderate positive correlation between RDI
(which also indices the micro-arousals related to the respiratory effort) and both the SD (r=0.367; p=0.039) and
the amplitude (r=0,365; p=0,04) of the glucose values.
Conclusions: The severity of OSA is associated with the night-time glucose variability in patients with the
MetSyn. Higher glucose variability may increase the oxidative stress that can worsen the casdiovascular outcomes
of patients with the MetSyn comorbid OSA.
Program: Fluid and electrolyte balance in healthy and pathological regulation of blood pressure and
circulation
Supervisor: István Mucsi
75
E/IV-12
THE ATHLETE’S HEART
Zsuzsanna Major1, Zsuzsanna Kneffel2, Tímea Kováts3, Eszter Csajági1
1
2
3
Faculty of Physical Education and Sport Sciences, Semmelweis University, Budapest
Qatar University, Doha
Introduction: The athlete’s heart undergoes morphological and functional changes as a result of long-term
training.
Left ventricular dimensions, wall thicknesses and function are echocardiographic measurements widely used in
clinical and in research, but the morphological and the functional adaptation of the right ventricle remains
unknown.
The aim of this study was to assess left and right ventricular function and enlargement in elte athletes and in
healthy sedentary non-athletes.
Methods: The study population consisted of 20 elite highly-trained male athletes and 15 age-matched healthy
non-athletes.
In addiction, left and right ventricular systolic (S’) and diastolic functions (E peak, A peak, E/A ratio, E’, A’
velocities and E’/A’ ratio) were determined by conventional PW Doppler echocardiography and Pulsed wave
Tissue Doppler imaging at the septal and lateral corners of the mitral and tricuspid annulus. Right and left
ventricular longitudinal diameters were also determined.
Results: The group of athletes showed highly but not statictically significant velocity of mitral and tricuspid E
(p<0,5; p<0,6) wave, and the tricuspid E/A (p<0,4) ratio than non-athletes. Mitral and tricuspid annulus Am
(both p<0,005), and Aa (p<0,0001 and p<0,001) were significantly smaller in athletes than in non-athletes.
Em/Am ratio (both p<0,05), and Ea/Aa on either side (p< 0,001 and p<0,005) were significantly higher in athletes
than in controls. We found significant difference between the two groups in the left ventricular longitudinal
dimensions (p<0,05). In the end-diastolic dimension of the right ventricle between the two groups proved to be
significant as well (p<0,05).
Regular and extensive training results in similar changes in right ventricular morphology and function to that of
the left ventricle.
Doctoral School: Sport Sciences
Program: Training and adaptation
Supervisor: Gábor Pavlik
76
2012. április 12-13.
E/IV-13
DIFFERENT MITOCHONDRIAL BIOGENESIS TO EXERCISE
TRAINING IN LOW AND HIGH EXERCISE RESPONDER RATS
Orsolya Marton1, Erika Koltai1, Ferenc Torma1, Steven Britton2, Lauren Koch2, Zsolt Radák1
1
2
Faculty of Physical Education and Sport Sciences, Semmelweis University, Budapest
University of Michigan, Ann Arbor, MI, USA
It is well-known everybody adapted with differ magnitude to the same exercise stimuli. Twin-studies have shown
that trainability is partly dependent on genetics. We studied rats which have been shown to react differently to
aerobic exercise training. Mitochondrial biogenesis in the skeletal muscle is obligatory to cope with the metabolic
challenge given by physical exercise.
Aim of the study: 27 selective breeding 11th generation for LRT and HRT rats were subjected to treadmill
running at 70% of VO2max. Animals were divided into 4 groups: low responder control (LRTC) and exercise
trained (LRTE) and high responder control (HRTC) and exercise trained (HRTE). We have measured some
physiological parameters, such as VO2max, gripping force, running distance during VO2max measurements, etc.
Moreover, we have measured the content/activity of some of the key proteins that are playing a key role in
mitochondrial biogenesis.
Results: VO2max and running distance were significantly higher in both of the exercise groups. The level of
nuclear respiratory factor-1 (NRF-1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha
(PGC-1α) decreased in LRTE group but increased in HRTE group compared to control groups by effect of
exercise. Content of mitochondrial transcription factor A changed similarly to NRF-1 and PGC-1. Exercise
resulted in decreased level of fusion protein, Mfn1, while increased the level of fission protein, Fis1. We
measured significant increasing the levels of peroxisome proliferator-activated receptor γ in LRTC and HRTE
groups, indicating a shift in basic metabolic processes.
Conclusion: Our data suggest that one of the reasons of different response to aerobic exercise training is due to
the different activation of proteins that are involved in the biogenesis of mitochondria.
Doctoral School: Sport Sciences
Program: Physical training, regulation, metabolism
Supervisor: Zsolt Radák
77
78
2012. április 12-13.
E/V
ORAL PRESENTATIONS
Chairman:
Dr. Árpád Dobolyi
79
80
2012. április 12-13.
E/V-1
PROTEIN-PROTEIN INTERACTIONS REGULATE THYROID
HORMONE ACTIVATION
Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine of the Hungarian
Thyroid hormone (TH) is a fundamental regulator of brain development and function. The human thyroid gland
secretes predominantly thyroxine (T4), a prohormone that gain access to the brain but cannot bind to the thyroid
hormone nuclear receptor. Thus T4 needs to be activated by type 2 deiodinase (D2), a tightly regulated ERresident protein degraded along the ubiquitin-proteasome pathway. A crucial element of ubiquitination is the E3
ligase ensuring specific delivery of ubiquitin to the target protein. This process allows rapid regulation of D2mediated T3 generation in the brain. Previous studies described the WSB-1 as an E3 enzyme involved in the
ubiquitination of D2, subsequently Teb4 was identified as another potential E3 ligase for D2 ubiquitination.
Our goal was to prove that the Teb4-D2 interaction occurs in living cells and identify the interacting protein
domains. We used acceptor-photobleaching based fluorescence resonance energy transfer (FRET). Furthermore
we assessed the role of Teb4 in the substrate-mediated acceleration of D2 ubiquitination. Finally, we set up a 3FRET approach to address the putative functional interplay between the WSB-1 and Teb4.
FRET was detected between N-terminus of Teb4 and D2 indicating that the Teb4 is part of the D2
ubiquitination protein complex. The T4-evoked acceleration of D2 ubiquitination increased the strength of D2Teb4 interaction demonstrating the contribution of Teb4 in substrate-mediated regulation of T3 generation. A 3FRET approach revealed that increase of D2 association to Teb4 or WSB-1 was similar upon T4 treatment. This
T3 regulator mechanism could play an important role in hypothalamic tanycytes, where D2 is coexpressed with
Teb4 and WSB-1. Since these self-renewing cells form the highly active T3 generating center in the mediobasal
hypothalamus and provide T3 for this brain region, the presented interactions could impact both T3-dependent
actions of hypothalamic neurosecretory neurons and the proliferatory potential of tanycytes.
Doctoral School: „János Szentágothai” Neurosciences
Program: Neuroendocrinology
Supervisor: Balázs Gereben
81
E/V-2
FASTING-INDUCED ALTERATIONS IN THE Α-MSH- AND AGRPIMMUNOREACTIVE INNERVATION OF TRH-SYNTHESIZING
NEURONS IN THE HYPOTHALAMIC PVN
Andrea Kádár1, Edith Sanchez2, Balázs Gereben1, Ronald M. Lechan3, Csaba Fekete1,3
1
2
3
Department of Endocrine Neurobiology/Institute of Experimental Medicine, Hungarian Academy
of Sciences, Budapest
Direccion de Investigaciones en Neurociencias/Instituto Ramon de la Fuente Muniz, Mexico
Department of Endocrinology/Tufts Medical Center, Boston, MA, USA
The activation of α-MSH neurons in the arcuate nucleus plays important role in the development of refeeding
induced satiety. These anorexigenic neurons innervate the hypophysiotropic TRH neurons in the hypothalamic
paraventricular nucleus (PVN) involved in the regulation of thyroid function. While refeeding of fasted rats
activates the neurons of the ventral parvocellular part of the PVN within 2h through the activation of the α-MSH
neurons, the TRH neurons are activated only 24h after the reindtroduction of food.
To determine the mechanism of fasting-induced melanocortin resistance of TRH neurons during the early phase
of refeeding, we performed triple-labeling immunofluorescence on double-transgenic TRH/Cre-Z/EG mice. By
confocal microscopic analyses we studied whether the number of α-MSH- and AGRP-immunoreactive axon
varicosities contacting hypophysiotropic TRH neurons differ under fed and fasted conditions.
A dense network of AGRP- and α-MSH-immunoreactive axons was found in PVN surrounding TRH neurons in
both fed and fasted mice. In fed mice, 30.9±0.3 AGRP-containing boutons and 19.3±0.4 α-MSH-containing
boutons were found on the surface of the perikarya and first order dendrites of the TRH neurons in the PVN.
Fasting caused a significant increase in the number of AGRP-IR varicosities on the surface of these cells
(44.9±0.3, P<0.001), but decreased the number of α-MSH-IR varicosities (13.6±0.7, P<0.001). Therefore,
fasting resulted in a more than two-fold increase in the ratio between AGRP and α-MSH-IR varicosities on the
surface of TRH neurons (Fed vs. fasted: 1.6±0.02 vs. 3.3 ± 0.2; P<0.001). As AGRP is an endogenous antagonist
of α-MSH, we hypothesize that the fasting-induced increase in the ratio between the AGRP and α-MSHcontaining input to hypophysiotropic TRH neurons contributes to the delayed recovery of these neurons.
Supervisor: Csaba Fekete
82
2012. április 12-13.
E/V-3
A REDUCTION IN THE ACTIVITY OF ALPHA-KETOGLUTARATE
DEHYDROGENASE COMPLEX DECREASES MATRIX SUBSTRATELEVEL PHOSPHORYLATION AND PROMPTS RESPIRATIONIMPAIRED MITOCHONDRIA TOWARDS EXTRAMITOCHONDRIAL ATP
CONSUMPTION
Gergely Kiss1, Csaba Konrád1, Anatoly A. Starkov2, Hibiki Kawamata2, Giovanni Manfredi2, Steven
F. Zhang2, Gary E. Gibson3, M. Flint Beal2, Vera Adam-Vizi1, Christos Chinopoulos1,2
1
2
3
Department of Medical Biochemistry, Semmelweis University
Weill Medical College Cornell University, New York, NY, 10021, USA
Weill Cornell Medical College/Burke Medical Research Institute, White Plains, NY, 10605, USA
Provision of succinyl-CoA by the alpha-ketoglutarate dehydrogenase complex (KGDHC) is essential for
generation of matrix ATP (or GTP) by substrate-level phosphorylation catalyzed by succinyl-CoA ligase. A
decline in KGDHC activity has been associated with a number of neurodegenerative diseases. The focus of this
association has been biased towards the diminished provision of reducing equivalents, and the extent of reactive
oxygen species formation. Here we show that transgenic mice with a deficiency in the dihydrolipoyl
succinyltransferase (DLST) or dihydrolipoyl dehydrogenase (DLD) subunit of KGDHC exhibiting a 25-40%
decrease in activity, prompted respiration-impaired i) isolated, ii) in situ synaptic and iii) in situ neuronal somal
mitochondria towards extramitochondrial ATP consumption. This was attributed to a shift in the reversal
potential of adenine nucleotide translocase towards more negative values due to diminished matrix substrate-level
phosphorylation, thus causing the translocase to reverse prematurely in respiration-impaired mitochondria of
DLST+/- and DLD+/- mice. These results were further corroborated by the finding that mitochondria from
WT mice respiring on substrates that supported substrate-level phosphorylation, exhibited higher ADP-ATP
exchange rates compared to those obtained from DLST+/- and DLD+/- mice. We propose that KGDHCassociated pathologies are subserved by the inability of respiration-impaired mitochondria to rely on “in-house”
mitochondrial ATP reserves.
Program: Functional neurosciences
Supervisor: Christos Chinopoulos
83
E/V-4
MONOCARBOXYLATE-TRANSPORTER-8 AND TYPE 3 DEIODINASE
IN AXON TERMINALS OF THE MEDIAN EMINENCE ALLOW SYSTEMSPECIFIC REGULATION OF T3-ACTION IN HYPOTHALAMIC
HYPOPHYSIOTROPIC NEUROSECRETORY NEURONS
Petra Mohácsik1, Imre Kalló1, Barbara Vida1, Anikó Zeöld1, Zsuzsanna Bardóczy1, Erzsébet
Farkas1, Andrea Kádár1, Antonio C. Bianco2, Zsolt Liposits1, Csaba Fekete1, B. Gereben1
1
2
Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy
Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of
Medicine Miami, FL USA
The hypothalamic neurosecretory neurons are crucial regulators of metabolism, growth, stress and reproduction.
These cells represent a major target of hypothalamic thyroid hormone signaling. Monocarboxylate-transporter-8
(MCT8)-mediated transport of thyroid hormone across the plasma membrane followed by its inactivation by type
3 deiodinase (D3) represents two limiting factors regulating neuronal T3 levels. We previously found D3immunoreactivity in axon varicosities of the external zone of the rat hypothalamic median eminence where the
enzyme was localized to dense-core vesicles in hypophysiotropic axon varicosities. We investigated whether
MCT8 could allow T3 influx directly to axon terminals and quantified the co-existence of MCT8 and D3 in
specific neurosecretory systems using immunofluorescent, confocal microscopy. MCT8-immunoreactivity was
observed on the surface of the vast majority of all types of hypophysiotropic terminals in the median eminence.
However, D3 was present in 71.8 ± 3.8% of axon varicosities containing GnRH, 63.2 ± 7.5% of CRH and 64.2
± 2.7% of GHRH, but only in 26.6 ± 5.0% of that containing TRH, while completely absent from somatostatincontaining neurons. To determine whether D3 is functionally active in this location, we studied whether D3mediated catalysis and T3-mediated D3 regulation is functional in the axonal compartment.
D3
homodimerization, a pre-requisite for D3 activity, was detected in cellular processes of GnRH expressing GT1-7
cells using a Bimolecular Fluorescence Complementation approach. Furthermore, D3 activity was induced 4-fold
in the median eminence of hyperthyroid rats, showing that axonal D3 responds to an elevated T3 influx. These
observations suggest fine-tuned and system-specific thyroid hormone metabolism in different types of
hypophysiotropic axons that involve MCT8-mediated transport and D3-catalyzed inactivation. This pathway may
represent a novel, regulatory pathway for T3-mediated hypothalamic function with potential effects on the
control metabolism, growth, stress and reproduction.
Petra Mohácsik is recipient of a Fellowship for Young Researchers
Institute of Experimental Medicine of the Hungarian Academy of Sciences
Supervisor: Balázs Gereben
84
2012. április 12-13.
E/V-5
AGING COINCIDES WITH MORPHOLOGICAL ALTERATIONS OF
KISSPEPTIN AND NEUROKININ B NEURONS IN THE INFUNDIBULAR
NUCLEUS OF THE HUMAN MALE
Csilla S. Molnár1, Barbara Vida1, Máté Sipos1, Imre Kalló1,3, Philippe Ciofi2, Beáta Borsay4,
Stephen R. Bloom5, Mohammad A. Ghatei5, Waljit S. Dhillo5, Zsolt Liposits1,3, Erik Hrabovszky1
1
2
3
4
5
Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy
INSERM U862, Neurocentre Magendie, Bordeaux, France
Department of Neuroscience, Faculty of Information Technology, Pázmány Péter Catholic
Department of Forensic Medicine, Faculty of Medicine of the University of Debrecen, Hungary
Department of Investigative Medicine, Hammersmith Hospital, Imperial College London, London,
United Kingdom
Growing evidence from studies in laboratory animals indicates that the gonadotropin-releasing hormone (GnRH)
neurosecretory pulses are strongly influenced by peptidergic neurons that co-synthesize kisspeptins with
neurokinin B (NKB) and dynorphins in the arcuate (infundibular; Inf) nucleus. In several species, the expression
of kisspeptins and NKB in this nucleus is negatively regulated by sex steroid hormones. From this we predicted
that the slow and moderate decline of blood testosterone in aging human males might also enhance kisspeptin
and neurokinin B synthesis in the Inf. This hypothesis was tested via a series of immunohistochemical
experiments on hypothalamic sections of 18 human male individuals that were divided into arbitrary „young”
(21-46 ys; N=10) and „aged”(50-67 ys; N=8) groups. We found that in both age groups, NKB-immunoreactive
(IR) cell bodies of the Inf slightly outnumbered kisspeptin-IR perikarya. Unlike reported in rodents and ewes,
dynorphin A-IR cell bodies and fibers were extremely scarce in the human Inf independently of age. The
following age group differences were identified by ANOVA: The regional density of NKB-IR cell bodies was
significantly higher in the Inf of aged vs. young men. An even more robust age-related increase was observed in
kisspeptin cell numbers. Fibers containing the two neuropeptides also established more frequent axosomatic and
axodendritic contacts with GnRH neurons in elderly men; the mean number of NKB-IR appositions to GnRH
neurons increased by about 80%, whereas the frequency of kisspeptin-IR contacts increased by over 200% with
age. Collectively, the age-related enhancements in KP- and NKB cell numbers appear to be compatible with a
reduced testosterone negative feedback onto kisspeptin and NKB neurons of the Inf. The heavier kisspeptin and
NKB inputs to GnRH neurons may play a role in the slightly enhanced stimulation of the reproductive axis in
elderly men.
Supervisor: Erik Hrabovszky
85
E/V-6
ALTERNATIVE SPLICING OF EGFR ECD IN HUMAN MELANOMA
Eleonóra Imrédi
According to our current knowledge eighty percent of the known genes have one or more splice variants, which
are different from each other both in structure and in function. In molecular biological investigations, the
presence of splice variants are almost never taken into consideration, neither at protein (antibody) nor at nucleic
acid (primer, probe) level.
The epidermal growth factor receptor (EGFR - ErbB ) is a member of the EGF family. EGFR is activated by
multiple ligands including EGF, TGF-α, HB-FGF, which all bind to the homo- and heterodimer forms of the
receptor to activate its downstream signaling pathways (MAPK, Akt, JNK). The dimerisation of the receptor is
controlled by the extracellular domain (ECD), therefore its spatial structure has crucial importance in this
signaling process, and the mutated forms of the ECD are regarded oncogenic. Alternative splicing may result in
dramatically altered isoforms of the original protein therefore it may also significantly change its function as well.
Results. Our study group have previously described that in human melanomas besides the well-known EGFR
VIII splice-variant, there are three new variants: the EGFR ∆2,3, EGFR ∆4 and the EGFR ∆13,14. The variants
validated by PCR technique have significance only in that case if functional proteins are translated from them.
Aims. In order to prove the significance of these altered isoforms, we have designed customized antibodies to
search for functional proteins derived from the splice-variant sequences. In the near future we plan to map the
expression profile of different EGFR isoforms during the progression of human melanoma both in cell cultures
and clinical samples.
Doctoral School: Pathological Sciences
Program: Oncology
Supervisor: József Tímár
86
2012. április 12-13.
E/V-7
miRNA EXPRESSION PROFILE OF ADENOID CYSTIC CARCINOMA
OF SALIVARY GLANDS AND THE BREAST: PRELIMINARY RESULTS
Orsolya Kiss1, Anna-Mária Tőkés1, Sándor Spisák2, Eszter Gábori1, Anikó Bata1, Subramanian
Kumar1, Borbála Székely1, Attila Marcell Szász1, Janina Kulka1
1
2
Background: Adenoid cystic carcinoma (ACC) is a well known malignancy in the salivary glands. Histologically
identical tumors infrequently occur in the breast. Although ACC of the salivary glands (sACC) and of the breast
(bACC) have the same pathomorphology, the clinical behaviour of this tumor type differs significantly in the two
organs. Exploring the molecular differences between the sACC and bACC has been in the focus of research in
the last decade, but to date to our best knowledge there is no scientific explanation for their different clinical
course.
Aim: In our pilot experiment, our aim was to define the miRNA expression pattern of selected sACC and bACC
cases and their normal adjacent tissues (NAT) to possibly identify underlying posttranscriptional mechanisms
which could explain their different clinical behaviour.
Results: Expression of 275 miRNAs has been detected in at least a single sample and 57 miRNAs were expressed
in all four sample groups. Compared to their corresponding NATs, 92 miRNAs in bACC tissues were
upregulated and 42 downregulated, while in sACCs 37 miRNAs were up- and 30 downregulated. Only our sACC
samples showed miR-181a-2*-expression, while miR-1234 was presented in all but sACC samples. In contrast,
miR-15a expression was detectable in each investigated tissue except bACCs.
Conclusion: Based on our preliminary findings, sACC and bACC have relatively different miRNA-profiles.
Identification of those genes which are affected by miR-181a-2*, miR-1234 and miR-15a, might bring us further
in the understanding of their exact function and possible roles. Target validation on a large set of samples may
finally reveal the enigma of the histomorphological appearance and related clinical course of ACC of breast and
salivary glands.
Acknowledgement: Erzsébet Azumah and Erika Samodai for technical assistance, Norbert Lippai MD and Anna
Szilágyi MD for sending the breast cases for consultation.
TÁMOP-4.2.2/B-10/1-2010-0013; TÁMOP-4.2.1/B-09/1/KMR-2010-0001
Program: Alterations of cells, fibres and extracellular matrix and diagnostic pathomorphological studies in
the course of heart and vascular diseases and in certain tumours
Supervisor: Janina Kulka
87
88
2012. április 12-13.
E/VI
ORAL PRESENTATIONS
Chairmen:
Prof. Dr. István Bitter
Dr. János Réthelyi
Dr. Róbert Bódizs
89
90
2012. április 12-13.
E/VI-1
BEHAVIOURAL-EPIDEMIOLOGICAL ANALYSIS OF ADOLESCENTS’
SMOKING IN A POPULATION OF A SMALL TOWN BETWEEN 2008
AND 2010
Mate A. Balazs1,2, Bettina F. Piko2
1
2
University of Debrecen, Medical and Health Science Center, Faculty of Medicine
University of Szeged, Faculty of General Medicine, Department of Behavioural Sciences
Keywords: adolescence, problem behaviour, smoking, risk factors
Smoking is one of the most severe public health concerns all over the world. It is especially true in case of
Hungary, because Hungary ranks first in terms of morbidity and mortality caused by smoking. The adolescence is
very important life period in relation to smoking and other addictive substances, as the young population meets
first these substances in this critical life period, and the regular use and abusing of them also begins in this age
group. More attention should be paid to adolescents’ smoking in the field of prevention, health promotion and
mental hygiene because of the widespread use and its harmful health effects. The study was performed in all of
the elementary and high schools of Mako and the villages in its area in Hungary. The pupils of grade 8 and 12
were questioned anonymously in 2008 and 2010; we create a subsample from the 2010 data according to criteria
of the study of 2008, because it consisted of other age groups too. The study of 2008 consisted of 546 pupils, and
the study of 2010 consisted of 534 pupils, the final sample was composed of 1080 pupils. Self-administered
questionnaires were applied. The survey included sociodemographic variables, lifetime and monthly prevalence of
smoking, beliefs and attitudes related to substance use. Cross-tabulations and chi–square tests were used to test
these interrelationships with SPSS MS 19.0 statistical program.
Aims: The purpose of the present study was to compare results of two studies in terms of data about smoking
and its influencing factors.
Results: According to comparison the worsening tendency, increasing substance use is present in case of both
frequency and quantity. In relation to different sociodemographic factors, for instance gender, age, parental
education status, commuting status, place and type of school significant changes were detected in comparison
with 2008.
Doctoral School: University of Szeged
Supervisor:
Bettina F. Piko
E-mail:
[email protected]
91
E/VI-2
SUBTHRESHOLD PSYCHIATRIC CONDITIONS IN CHILD
PSYCHIATRY: A LONGITUDINAL STUDY
Eszter Anna Bertha
Vadaskert Child Psychiatry Hospital, Budapest
Objectives: The majority of psychiatric disorders start in childhood and adolescence, many times in
subthershold form. Subthreshold disorders can be risk factors for full-syndrome (FS) disorders, therefore ealy
recognition is important. This 5-year longitudinal study assessed the prevalence, development and comorbidities
of subthreshold and FS disorders in childhood and adolescence.
Methods: A total of 418 subjects from clinical population (CP), and 56 participants from general population
(GP) completed the initial assessment between 2006-2007 (T1) in Vadaskert Hospital. All subjects had to be
under age 18. The follow-up recruitment was started in 2011 (T2) and so far a total of 75 subjects (CP: n=61,
GP: n=14) returned for readministration. Diagnoses were made by the Mini International Neuropsychiatric
Interview Kid. Subthreshold disorders were defined as the presence of at leat one core symptom accompanied by
one or more additional symptoms with the original time-limits. We applied chi2-test (χ2) for statistical analyses.
Preliminary results: In the CP the majority of cases had at least one subthreshold disorder (T1: 94%, T2: 81% ).
In the GP these percentages were lower (T1: 51%, T2: 53%). Of the clinical subjects, 47% in T1, 54% in T2 had
suicidal ideations, 45% in T1, 43% in T2 had subthreshold depression (sD), and 13% in T1, 25% in T2 had FS
depression. In both assessments subjects with sD in significantly higher proportion had subthreshold generalized
anxiety (T1: χ2=8.073, df=1, p<0.05; T2: χ2= 9.804, df=1, p<0.05), and in T2 subjects with sD in significantly
higher proportion had suicidal ideations (χ2= 4.291, df=1, p<0.05) than subjects without sD.
Conclusions: The rate of subthreshold conditions is high in child-psychiatry. The comorbidities can be stable
over time. Since subthreshold disturbances can result more complex disorder-features, the assessment of
subthreshold disorders need to be included into the diagnostic work-up.
Doctoral School: Mental Health Sciences
Program: Clinical psychology and psychiatry
Supervisor: Judit Balázs
92
2012. április 12-13.
E/VI-3
RELATIONSHIP BETWEEN PSYCHOLOGICAL RISK FACTORS AND
SOMATIC FACTORS IN ACUTE CORONARY SYNDROMES
Beatrix Rafael1,2, Piroska Balog3
1
University of Szeged, Psychiatric Clinic
Special Hospital of Chest Illnesses, Cardiology Rehabilitation Department, Deszk
3
Semmelweis University Faculty of Medicine, Institute of Behavioral Sciences, Bp.
2
Purpose: The aim of this study was to examine psychological risk factors in patients after acute myocardial
infarction who took part in residential cardiac rehabilitation. We proposed to study the relationship between
somatic factors and psychological risk factors, and possible gender differences.
Methods: In patients (N=97, 30 women, 67 men, 30-81 years old) the level of depression and anxiety (Beck
Depression Inventory /BDI/, Spielberger Trait Anxiety Inventory /STAI-T/), vital exhaustion (Maastricht
Questionnaire /MQ/) and sleep disturbances (The Athens Insomnia Scale /AIS/) were assessed. Left ventricular
ejection fraction /LVEF/, left ventricular diastolic diameter /LVDD/, Body Mass Index /BMI/, METs and the
number of diseased vessels were retrieved from medical records.
Results: 48% of patients showed depressive symptoms, 39% had high level of anxiety, 41% were vitally
exhausted and 24% of them had sleep complaints. The level of anxiety in women was significantly higher than in
men (45.91 vs. 40.98, p=0.05) however we could not find a significant difference in other psychological risk
factors. The connection between LVEF, LVDD and the number of diseased vessels, and psychological risk
factors was not statistically significant. The MET value showed a significant linear correlation with BDI (r= -0.2,
p=0.03), MQ (r= -0.23, p=0.02) and AIS (r= -0.22, p< 0.009) scores. After adjustment for psychological risk
factors and other physical parameters sleep disturbances (AIS) were found to have a significant correlation with
METs (R= -0.26, p=0.008). The BMI score showed significant linear correlation with all psychological risk
factors: BDI (r=0.43, p<0.001), STAI-T (r=0.31, p=0.004), MQ (r=0.33, p=0.001) and AIS (r=0.43, p<0.001).
According to multivariable regression model only sleep disturbances showed correlation with BMI scores (R=
0.4, p<0.001).
Conclusions: Our investigation revealed some new psychological risk factors among patients after myocardial
infarction. Sleep disorders are particularly important and we demonstrated its correlation with BMI and exercise
capacity.
Program: Behavioral sciences
Supervisor: Piroska Balog
93
E/VI-4
OBSTETRICAL AND GYNECOLOGICAL CONSEQUENCES OF
EATING DISORDERS
Eating disorders mainly affects women in adolescence or in young adulthood. These psychosomatic disorders
which appears at a critical phase of women’s reproductive life can cause numerous consequences on women’s
sexual cycle, fertility, pregnancy and pregnancy outcome, the development of the foetus and on the postpartum
period as well.
Menstrual abnormalities and fertility problems are common in those who are significantly underweight or can be
characterised with severely disrupted eating. Amenorrhoea is one of the diagnostic criteria of anorexia nervosa.
Beside menstrual irregularities and secondary amenorrhoea the polycystic ovarium syndrome is more frequent in
bulimia nervosa. We can found a higher rate of eating disorders among women in fertility clinics.
Eating disorder symptomatology mostly decreases during pregnancy but a recurrence is typical after delivery.
Anxiety and depression is more frequent than average during pregnancy and in the postpartum period as well
among women with eating disorders.
Obstetrical complications, caesarean section, and (in bulimia nervosa) the miscarriages are prevalent. Offsprings
have lower birth weight and lower Apgar scores. Perinatal death and abnormalities in foetus’ development is
more frequent (e.g. cleftlip). Psychological sypmtoms of eating disorders, an excessive fear of fatness and a
distorted body image can affect the attitude to breastfeeding negatively. Maternal poor nutrition and stress cause
hormonal changes which can lead altering the development of the foetus in later life. Intrauterine undernutrition
and perinatal stress can make one sensivite for the development of an eating disorder in the future.
This presentation reviews the obstetrical and gynecological consequences of eating disorders.
Supervisor: Ferenc Túry
94
2012. április 12-13.
E/VI-5
ADVERSE LIFE EVENTS AND SUICIDE RISK IN PEOPLE WITH
SCHIZOPHRENIA
Krisztina Kocsis-Bogár1,2, Dóra Perczel-Forintos1, Mónika Miklósi2
1
2
Faculty of Clinical Psychology, Semmelweis University, Budapest
Department of Clinical Psychology, Semmelweis University, Budapest
Aims: Our aim is to examine the interconnections of suicidal behaviour (thoughts and attempts) and impact of
adverse life events and consequential dissociation. Our hypothesis is that patients with higher impact of adverse
events show higher dissociation and hopelessness and are at higher risk of suicide attempts.
Background: Suicide rates amongst people with schizophrenia have been estimated 5-10%. Almost 50% of
patients attempt suicide at least once in their lifetime. Major risk factors are considered to be higher IQ, male
gender, white race, isolation and depressive symptoms, impulsivity, a greater number of hospitalizations, noncompliance, parasuicidal behaviour, substance abuse and hopelessness. Adverse life events have been found to be
associated with increased suicide risk in people with schizophrenia and other mental illnesses. According to
several studies, adverse life events (especially in childhood) are connected to higher rates of dissociation and
higher suicide risk.
Methods: We are planning to include 30 patients with schizophrenia in our study. Questionnaires: SCID-I
diagnostic interview (First, M. B., Spritzer, R. L., Gibbon, M, Williams, J. B. W, 2000. Hungarian adaptation:
Szádóczky et al., 2004), Impact of Event Scale (Horowitz et al. 1979, Hungarian adaptation: Annus et al., 2005),
Oxford-Liverpool Inventory of Feelings and Experiences (Mason, Claridge and Jackson, 1995), Dissociative
Experiences Scale (Carson and Putnam, 1993), Hopelessness Scale, shortened version (Beck et al., 1974, Perczel
Forintos et al., 2001), Beck Depression Inventory shortened version (Beck and Beck, 1972; Kopp and Fóris,
1993).
Results: Statistical analysis is going to be performed with SPSS 20.0
Supervisor: Dóra Perczel Forintos
95
E/VI-6
EFFECTS OF CURRENT ALCOHOL AND TOBACCO CONSUMPTION
ON PHYSICAL AGGRESSION AND ADHD SYMPTOMS AMONG
HUNGARIAN ADOLESCENTS
Balázs Matuszka1,2, Erika Bácskai2, József Gerevich2,3
1
2
3
Mental Health Sciences Doctoral School, Semmelweis University
Addiction Research Institute
Faculty of Orthopedagogics, Eötvös Lóránd University, Budapest
Aim of the study: To investigate the severity of physical aggression, ADHD symptoms and the co-occurrence
of alcohol drinking and tobacco smoking among 15 year old adolescents.
Study design and setting: A cross sectional survey was performed to assess the co-occurrence of alcohol and
tobacco consumption and ADHD symptoms and physical aggression among ninth grade students. The study was
conducted in public schools in Budapest, including pupils of all three common types of schools (grammar school,
vocational school, and industrial school). The final sample, which consisted 944 pupils, was representative for
school types available in Budapest.
Measurements: The Buss-Perry Aggression Questionnaire (AQ) Physical Aggression (PA) Subscale, the ADHD
Rating Scale-IV and the substance use-specific items of European Version of the Adolescent Assessment
Dialogue (EuroADAD), were used for measures.
Results: GLM analyses, adjusting for school types, indicated that pupils who drunk alcohol and smoked tobacco
at least once a week (current users) had significantly higher severity of overall physical aggression, as well as
ADHD symptoms than students who did not use such substances (not current users). The highest severity of
aggression was observed among boys who were current alcohol drinkers and tobacco smokers. The most severe
ADHD symptoms were identified among current co-user girls. The lowest severity of physical aggression was
detected among girls, who were not consuming alcohol nor tobacco. The co-occurrence of alcohol and tobacco
use had a more significant effect on the severity of ADHD symptoms than the given form of education.
Conclusions: Considering the prevalence of school violence and the co-occurrence of tobacco smoking and
alcohol drinking, our results suggest that tobacco and other substance use prevention programs should include
strategies of bullying and violence-reduction in schools.
Supervisor: József Gerevich
96
2012. április 12-13.
E/VI-7
THE EFFECT OF PERCEIVED PARENTAL EFFICACY ON PARENTS’
GENERAL DISTRESS AFTER THEIR CHILD’S SURGERY
Mónika Miklósi1, Elvira Galambosi2
1
2
Heim Pál Pediatric Hospital, Budapest
Keywords: perceived parental efficacy, parental distress, pediatric surgery
Background: Perceived parental efficacy (PPE) – the caregivers’ beliefs in their ability to parent successfully –
was evidenced to play an important role in parent and child adjustment in non-medical settings. Cognitive
behavioural interventions targeting PPE were shown to be effective in reducing distress in a sample of parents of
very young children (between age 2 and 7 years) after their child was admitted to the paediatric intensive care
unit. However, the relationship between PPE and parents’ distress has not been studied in other medical samples.
Objective: This study aimed to explore the role of perceived parental efficacy on parents’ general distress in the
first 24 hour after child’s planned surgery.
Method: In a prospective longitudinal design, parents of 114 children (aged from 6 months to 17 years) admitted
to the Heim Pál Pediatric Hospital for planned surgical interventions completed a demographical form and the
Parental Belief Scale for Parents of Hospitalized Children (PBS), as a measure of perceived parental efficacy, one
to seven day(s) before hospitalization. In 24 hours after their child’s surgery, parents also filled out the State
subscale of the Spielberger State-Trait Anxiety Inventory (STAI-S). Multiple regression analysis was conducted to
detect the impact of the PBS scores on parents’ state anxiety, controlling for child’s age and gender, parent’s level
of education (low, medium, high), length of stay in hospital (≤ 24 or >24 hours), and previous hospital
experiences (yes/no).
Results: In a significant model (F=2.226, df=113, p=.038), which accounted for 12.8% of the variance, PBS
scores significantly negatively predicted state-anxiety (β=-.267 p=.006) whereas demographical and
hospitalization variables were not associated with parents’ general distress (p>.05).
Conclusions: Our results underline that parents’ beliefs about their ability of parenting their children during
hospitalization play a crucial role in parents’ adaptation to their child’s planned surgery. Interventions targeting
perceived parental efficacy might prevent or reduce general distress in parents whose children undergo surgery,
and might be adapted to all age-groups of children.
97
E/VI-8
BEHAVIOURAL INHIBITION AND IMPULSIVITY IN ADULT ATTENTION
DEFICIT HYPERACTIVITY DISORDER
Szilvia Papp1, László Tombor1, Brigitta Kakuszi1, Lívia Balogh1, Viktória Simon 1, Pál Czobor1,2
1
2
Department of Psychiatry and Psychology, Semmelweis University, Budapest
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA
Background: ADHD is common childhood neuropsychiatric disorder, characterised by inattention, motor
restlessness and impulsive behaviour. Evidence shows that ADHD persists into adulthood in a high proportion
of cases1. Impulsivity and the inability to inhibit a prepotent tendency to respond (behavioural response
inhibition) are prominent features of the disease. Since this can account, at least in part, for the functional
impairment in the daily lives of patients, its investigation in adult ADHD is of high importance2.
Aims: The objective of this study was to investigate whether ADHD subjects differ on objective measures of
behavioural response inhibition and whether there is an association between these measures and symptoms of
impulsivity.
Method: In order to examine deficiencies in impulsivity and emotional self-regulation, and to examine the
association of these deficiencies with behavioural inhibition we used the International Affective Picture System
(IAPS)3. Pictures were presented in a random sequence in a Go/No-Go trial. Participants were asked to respond
as quickly and accurately as possible to each stimulus, but withhold response to the second instance of any
stimulus that is repeated. Barratt Impulsiveness Scale (BIS) was obtained from both patients and controls.
Subjects included patients with the DSM-IV diagnosis of adult ADHD (n=38) and healthy controls (n=32),
matched for age, gender and level of education.
Results: Generalized linear model analysis indicated a significantly (p<.05) higher proportion of behavioural
response inhibition (commission errors) in adult ADHD subjects compared to controls. Logistic regression
showed that the likelihood of errors increased as a function of BIS severity.
Conclusions: Consistent with previous findings our results underlined that behavioural inhibition is
compromised in adult ADHD, and the extent of deficit is proportional to subjective measures of symptom
severity. These findings may help identify a specific subgroup of ADHD, which may be more prone to impaired
quality of life.
Supervisor: Pál Czobor
98
2012. április 12-13.
E/VI-9
QUANTITATIVE EEG IN ADULT ATTENTION DEFICIT/
HYPERACTIVITY DISORDER (ADHD)
László Tombor1, Szilvia Papp1, Brigitta Kakuszi1, Lívia Balogh1, Viktória Simon 1, Pál Czobor1,2
1
2
Department of Psychiatry and Psychology, Semmelweis University, Budapest
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA
Background: Attention Deficit Hyperactivity Syndrome is a childhood-onset neurodevelopmental disease which
often persists for adulthood and is accompanied with several psychiatric comorbidities. Diagnosis of ADHD is
still controversial, mainly based on self-reported behavioral symptoms. A growing body of (mainly pediatric)
literature suggests that quantitative EEG measures might be useful for differentiate between patients and healthy
subjects.
Aims: Our objective was to investigate quantitative electrophysiological indices including total, absolute and
relative power in adult ADHD patients and healthy controls in order to identify group differences.
Methods: Thirty-eight adult ADHD patients and 32 healthy controls were included, matched for age, gender and
level of education. High density (128 channel) EEG was recorded in a resting state, with eyes open, and was
band-pass (0.05-70 Hz) and notch (48-52 Hz) filtered. Epochs containing biological or technical artifacts were
excluded. Epochs of 2500 ms duration were used for calculation of total, absolute and relative power in the
conventional clinical frequency bands including delta, theta, alpha and beta. EEG indices were calculated for 14
scalp areas, by averaging the data obtained from individual electrodes, in order to increase statistical robustness of
the estimates. Clinical data on symptom severity were also measured, using the Conner’s Adult ADHD Rating
Scale (CAARS). Comparison of the study groups was carried out by General Linear Model analysis using SAS 9.2
software.
Results: No significant difference in demographic variables occurred between study groups. Our results indicate
that patients with adult ADHD display a significantly higher power in the alpha band compared to healthy
controls. Furthermore, hyperactivity symptoms on CAARS showed a significant (p<.05) relationship with the
amount (positive correlation) and frequency (negative correlation) of alpha activity.
Conclusions: Our findings are consistent with previous results from pediatric literature that quantitative EEG
might be a useful tool for differentiating of ADHD and healthy subjects.
99
E/VI-10
SUICIDAL BEHAVIOR: PSYCHOLOGICAL AND ETHNICAL
DIFFERENCES IN THE SERIOUSNESS OF DELIBERATE SELF
POISONING
Mónika Ditta Tóth1, András Székely1, Szilvia Ádám1, Tamás Zonda2, Mária Kopp1
1
2
Semmelweis University, Budapest
Hungarian Association for Suicide-Prevention, Budapest
Objective: The aim of the study is to examine the psychological and sociocultural background factors of suicide
attempts in Borsod-Abaúj-Zemplén county, and in Budapest. Miskolc and its rural area was the intervention
region of the OSPI Suicide Prevention Program. In this study we also consider the ethnical differences in the
examined sample.
Method: The research was carried out in the Toxicology Departments of Miskolc County Hospital, and the
Péterfy Sándor Hospital in Budapest. We have interviewed 120 people during their hospitalization following their
attempt to commit suicide. As a method we used half-structured interviews in which we asked the patients about
their demographics, social and marital status, physical and mental illness. We asked in detail about the
circumstances, the reason and the method of their suicide attempt. They filled out the Shortened Beck
Depression Inventory and the Hopelessness Scale as well. Based on the interviews we were able to estimate the
seriousness of the suicide attempts.
Results: The main risk factors of suicidal behavior are: lack of a partner, and unemployment. Direct risk factors
are interpersonal conflicts (mainly with the partner and other family members), financial problems, grief, sleeping
disturbance followed by physical illness. Patients who considered themselves as a member of the Roma minority,
had significantly less serious parasuicide attempts, however there was no singificant difference between the level
of depression in the two groups. The amount of pills taken are two times higher in the non-Roma group. In the
Roma group financial problems are the number one direct risk factors, while in the non-Roma group conflict
with the partner is the main factor.
Conclusion: Considering the ethnicity in the background of suicidal behavior there are significant differences
between the Roma and non-Roma groups. In the field of suicide prevention it would be important to take these
distinctions into consideration to be more effective in both ethnical groups.
Supervisor: Mária Kopp
100
2012. április 12-13.
E/VI-11
ASSOCIATION BETWEEN LUNAR PHASE AND SLEEP
CHARACTERISTICS
Csilla Zita Turányi, András Szentkirályi, Mária Czira, Andrea Dunai, Julianna Szőcs,
Orsolya Véber, Katalin Rónai, Andrea Kelemen, Rezső Zoller, Márta Novák, István Mucsi
Objectives : There are few and contradicting results regarding the association between lunar phase and sleep, and
popular belief holds that the lunar cycle affects human physiology, behavior and health. Our aim was to examine
the relationship between lunar phases and sleep characteristics.
Methods : Data from 478 patients were analyzed in a cross-sectional survey, all patient had a kind of sleep
disorder, but we excluded patients with apnea-hypopnea index≥15/h. Socio-demographic parameters were
recorded. Data were analyzed using ANCOVA and K independent (Kruskal-Wallis) tests. All participants
underwent one-night standard polysomnography, bedrooms had no window.
Results: 57% of patients were males, mean age for men was 45±14 years and 52±12 years for women. Mean
sleep efficiency was 78,2%. 364 person slept during changing moon, 57 during full moon and 57 during new
moon, there were no significant differences regarding age and gender between groups. Among women full moon
phase was associated with lower sleep efficiency (p=.01), shorter sleep duration (p=.01) and REM duration
(p=.005) after adjustment for age. Self-reported fatigue in the morning (p=.05) and self-reported time of falling
asleep was higher during full moon (p=.04). Among men the sleep duration was significantly shorter at full moon
(p=.05), while other sleep variables showed no difference across moon phases.
Conclusion: Our results support the widely held belief that sleep characteristics may vary with the moon phase,
especially among women.
Supervisor: István Mucsi
101
E/VI-12
COMORBID FACTORS OF INDIVIDUALS WITH A TENDENCY TO
ORTHOREXIA NERVOSA
Márta Varga1, Szilvia Dukay-Szabó1, Ferenc Túry1, Eric F. van Furth2
1
2
Institute of Behavioral Sciences, Semmelweis University, Budapest
Center for Eating Disorders Ursula, Leidschendam, the Netherlands.
Keywords: orthorexia nervosa, eating disturbances, obsessive compulsive feature
Objective: Orthorexia nervosa (ON) (Bratman, 1997) can be defined as fixation on healthy food, or healthy
food dependence. It remains unclear what kind of disorder orthorexia nervosa (ON) is. It differs from other
eating disorders because the quality of the food is the object of the obsession and not the amount. There are
many obsessive and compulsive characteristics in ON. Several harmful behaviours and pathological fears and
worries about one’s health, eating behaviour and quality of food can lead to serious consequences affecting one’s
health and social relationships.
The aim of the current study is to analyze the comorbid factors of ON.
Methods: 656 individuals (mean age=29.74; SD= 9.94). filled out an online questionnaire including
sociodemographic data, the ORTO-15 (ON scale), the Eating Disorder Inventory (EDI), the Maudsley
Obsessive Compulsive Inventory (MOCI), the Beck Depression Inventory (BDI).
Results: Individuals with lower scores on the ON scale (determined by the cut-off point of one +1 SD; meaning
higher tendency to ON) reported significantly more frequent depressive symptoms (BDI), compulsive checking
(p<0.05), contamination fears and rumination on the scales of MOCI (p<0.01), compared to those having high
scores on the ON scale (those below 34.12). Compared with the high scorers on ON scale, the low ON scale
scorers also had significantly higher scores on all of the scales of EDI (p<0.01) excepting interpersonal distrust.
There was no significant difference in BMI scores between the two groups
Conclusions: Individuals with an ON tendency can be affected by other psychopathological problems, like
depression, which can be indicative of the presence of clinically significant distress or functional impairment in
ON. Both eating and body image related disturbances, and obsessive compulsive features are characteristic of
individuals with an ON tendency.
Further studies are needed to clarify the place of ON among the mental disorders.
Supervisor: Ferec Túry
102
2012. április 12-13.
E/VI-13
VARIANTS IN CATECHOL-O-METHYLTRANSFERASE GENE ARE
ASSOCIATED WITH IMPULSIVITY AND EXECUTIVE FUNCTION:
RELEVANCE FOR MAJOR DEPRESSION
Dorottya Pap1, Ian M. Anderson2, J.F. William Deakin2, Gyorgy Bagdy1, Gabriella Juhasz2
1
2
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis
Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical
and Human Sciences, The University of Manchester, UK and Manchester Academic Health
Sciences Centre
Introduction: Impulsivity is a complex personality trait generated intensive research interest because of its
crucial role in several neuropsychiatric disorders. Impulsivity also has a strong heritable component suggesting
that it represents an intermediate phenotype to identify genetic risk factors for relevant neuropsychiatric
conditions.
As recent studies indicated, impulsivity may be an important risk factor for major depression (1, 2). It can be
hypothesised that neurobiological mechanisms that lead to increased impulsivity also increase vulnerability to
depression. In our study we investigated the role of impulsivity and dopaminergic system in depression by
analyseing catechol-o-methyltransferase (COMT) gene in a population genetic study.
Methods: In first, four tagging SNPs in the COMT gene were genotyped in two independent population cohorts
in Manchester (n=1267) and Budapest (n=942), and subjects filled out validated questionnaires about depression,
impulsivity and neuroticism. Second we carried out diagnostic interviews in a well characterised subpopulation
(n=264) and measured the participants ability to inhibit prepotent behavioural responses with the Stop task. The
Stocking of Cambridge (SOC) task was used to investigate cognitive functions. To explore the complex interplay
between impulsivity, depression and COMT, we used structural equation modelling (SEM).
Results: Subjects with reported lifetime depression (RD) scored significantly higher on impulsivity both in
Manchester (p<0.001) and Budapest (p=0.006). In the interviewed population remitted depressed subjects also
scored higher on impulsivity (p=0.008).
Haplotype trend regressions showed significant effect of COMT on impulsivity in Manchester (pperm<0.05),
Budapest (pperm<0.05), and in combined cohorts (pperm<0.05), respectively. Haplotypes have similar direction of
effects in both populations. An opposite direction of COMT haplotype significant effect (p<0.05) can be seen on
executive function and on depressive symptom scores. There were no association between COMT and
neuroticism, RD or the Stop task.
Henceforward combined with genetic results, we tested a SEM model in the combined cohort. We hypothesised
that impulsivity would exert its effect through neuroticism, and through this, depressive symptoms and RD. In
the best fit model, we found both direct and indirect correlations between COMT and RD. As a next step, to
investigate the relationship between COMT, impulsivity and depression, we added cognitive function to the
model (interviewed dataset, measured by SOC). In the best fit model the effect of impulsivity on depression was
mediated either by neuroticism or by cognitive function.
Conclusion: Our main finding is that haplotypic variants in the COMT gene are associated with impulsivity in
two independent populations, and we also demonstrated that self-reported impulsivity is a possible trait marker
for depression.
Despite impulsivity being a trait factor for depression, the COMT effect on depressive symptoms showed the
opposite pattern to impulsivity in subjects without history of depression. This haplotypic association was similar
103
to the COMT effect on cognitive function. Indeed, SEM models demonstrated that COMT and impulsivity acted
both together, through neuroticism, and independently to increase the risk of depression and these effects were
modulated by cognitive function.
These results emphasize how important to investigate intermediate phenotypes in relation to genotypes to
interpret their relevance in the development of neuropsychiatric disorders.
1.
Benko A, Lazary J, Molnar E, Gonda X, Tothfalusi L, Pap D, Mirnics Z, Kurimay T, Chase D, Juhasz G, Anderson
IM, Deakin JF, Bagdy G. (2009). Significant association between the C(-1019)G functional polymorphism of the HTR1A
gene and impulsivity. Am J Med Genet B Neuropsychiatr Genet 153B(2): 592-599.
2.
Granö N, Keltikangas-Järvinen L, Kouvonen A, Virtanen M, Elovainio M, Vahtera J, Kivimäki M. (2007). Impulsivity
as a predictor of newly diagnosed depression. Scand J Psychol 48(2): 173-179.
Supervisor: György Bagdy
104
2012. április 12-13.
E/VII
ORAL PRESENTATIONS
Chairman:
Prof. Dr. Gábor Bánhegyi
105
106
2012. április 12-13.
E/VII-1
MODULATION OF EXPERIMENTAL MODELS OF AUTOIMMUNITY BY
Borbála Aradi1, Krisztina Pálóczi1, Petra Misják1, Bence György1, Tamás G. Szabó1, Ágnes Kittel2,
Szilvia Bősze3, Kata Horváthi3, Krisztina Holló4, Katalin Szabó-Taylor1, Mária Pásztói1, András
Falus1, Edit I. Buzas1
1
2
3
4
Institute of Experimental Medicine of the Hungarian Academy of Sciences
Department of Organic Chemistry, L. Eötvös University, Budapest
Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical and Health
Science Center, University of Debrecen
Background: Extracellular vesicles are 50-1000 nm sized membrane vesicles secreted by cells both constitutively
and upon stimulation. They play an important role in intercellular communication. We have shown recently that
thymus-derived extracellular vesicles carry numerous proteins implicated in immunity and immunological
tolerance induction.
Goals: To investigate whether thymus-derived extracellular vesicles may modulate the onset and/or severity of
different experimentalmodels of autoimmune diseases.
Methods: Extracellular vesicles (and vesicle populations) from syngeneic mouse thymuses were isolated by
differential centrifugation, size filtration and sucrose flotation. We have investigated the effect of thymus-derived
extracellular vesicles on proteoglycan-induced arthritis (PGIA), glucose-6-phosphate isomerase-induced arthritis
(GPIA) and experimental allergic encephalomyelitis (EAE).
Results: A single intravenous injection of vesicles did not affect the onset and severity of symptoms of mice
suffering from either GPIA or EAE. In contrast, in PGIA, a chronic experimental autoimmune model of human
rheumatoid arthritis, injection of thymus-derived extracellular vesicles reduced the total acute arthritic linical
scores as compared to arthritic mice without injection of vesicles. Furthermore, loss of extension in the ankle
joints, a measure of chronic arthritis, was strongly reduced in the vesicle-injected group.
Conclusion: These data suggest that extracellular vesicles may exert disease modifying effect in certain models of
autoimmunity.
Doctoral School: Molecular Medicine
Program: Basis of human molecular genetics and gene diagnostics
Supervisor: Edit Búzás
107
E/VII-2
INQUIRING ABOUT AVIAN THYMIC DENDRITIC CELLS
Ildikó Bódi
Department of Human Morphology and Developmental Biology, Semmelweis University, Budapest
Avian thymic dendritic cells histologically is not yet identified, but it is reasonable to assume its existence.
Although we have several dendritic cell markers (CD205, 74.3) which identify thymic cells but the distribution
and histological appearance of these positive cells showed a high rate similarity to that of the thymic epithelial
cells. This immunocytochemical observation initiated the introduction of anti-keratin staining into the inquiry of
the thymic dendritic cells. The distribution of cortical epithelial cells justified the findings obtained by CD205 and
74.3 monoclonal antibodies. Double immunofluorescence staining provided circumstancial evidence for the
colocalization of CD205 and 74.3 with the anti-keratin staining. Suprisingly, in the medullary area of the thymus
the anti-keratin and the anti- dendritic cell staining is not colocalized, suggesting that in the medulla the CD205
and the 74.3 mAbs recognize a keratin-free dendritic-like cell popoulation. These statements indicate a
cytological - and consequently functional - differences between cortical and medullary thymic epithelial cells. The
transmission electronmicroscopy of the chicken thymus proved, that the cortical epithelial cells produce
cytoplasmic granules, which could be the target of CD205 and 74.3 mAbs. Chick-quail interspecific chimeras
confirmed the immunohistochemical data and provided first time an experimental evidence, that thymic cortical
epithelial cells and dendritic cells share common intracytoplasmic antigenic epitop (s), which were recognized by
CD205 and 74.3 monoclonal antibodies.
Program: Embryology, theoretical, experimental and clinical developmental biology
Supervisor: Imre Oláh
108
2012. április 12-13.
E/VII-3
ASSOCIATION AND MOLECULAR ANALYSIS OF THE WFS1 GENE
Zsuzsanna Elek
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis
Introduction: Wolfram syndrome is a mongenic disease associated with juvenile onset diabetes mellitus and
optic atrophy caused by mutations of the WFS1 gene. On the other hand, SNPs of the gene have been suggested
to be in association with diabetes mellitus, despite their biological function has not yet been characterized
completely. According to our in silico studies, the rs9457 SNP in the 3’ untranslated region (3’ UTR) of the gene
alters miR binding which might be a causative connection between genetic constellation and phenotype.
Aims, methods: An association study was performed to analyze the possible association between the rs9457
SNP and diabetes mellitus. Real-time PCR based technique was employed for the genotype analysis, the study
included 376 patients with type 2 and 241 patients with type 1 diabetes as well as 1147 control subjects.
Functional role of the SNP was investigated by cloning the different 3’ UTR variants into luciferase reporter
system.
Results: The rs9457 miR SNP was associated with type 1 and type 2 diabetes (p = 0.0034, and p = 0.0008,
respectively). Functional studies applying an in vitro cell culture demonstrated that the miR185 bound to the 3’
UTR region of the WFS1 gene and decreased the amount of the generated protein in an allele-specific manner.
Our results suggest that polymorphic variants of the WFS1 gene could contribute to the genetic background of
diabetes mellitus. Association was earlier demonstrated between rs1046320 3’ UTR SNP and the disease,
however biological function of the polymorphism could not be proven. Taking our results together with the
strong linkage between the two SNPs, rs1046320 can be considered as genetic marker, whereas rs9457 SNP
might play a biological role in the regulation of translation. Our results might shed light on the association of
WFS1 variants and their function at molecular level.
Program: Pathobiochemistry
Supervisor: Zsolt Rónai
109
E/VII-4
IN VITRO AND CELLULAR STUDY OF EGFR – C-MET KINASE
INHIBITORS IN NSCLC CELL LINES
Pal Gyulavari1, Balint Szokol2, Ibolya Kurko1, Gyorgyi Bokonyi1, Gabor Borbely1,
Csaba Szantai-Kis2, Laszlo Orfi2,3, Istvan Petak1, Gyorgy Keri1,2, Tibor Vantus1
1
2
3
Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University,
Budapest
Vichem Chemie Ltd., Budapest, Budapest
Department of Pharmaceutical Chemistry, Semmelweis University, Budapest
Mutant EGFR (epidermal growth factor receptor) driven pathways are playing important role in NSCLC (nonsmall cell lung cancer). Mainly patients harbournig somatic activating mutations (eg. L858R) in EGFR respond
efficiently to currently applied EGFR TKIs (tyrosine kinase inhibitors). However, in most cases patients relaps,
due to secondary resistence mutations (eg. T790M) in EGFR, or amplification of the oncogene MET (hepatocyte
growth factor receptor gene).
Screening the molecular library of Vichem Ltd. in a recombinant kinase assay, we identified a TKI compound
family (N-[4-(quinolin-4-yloxy)-phenyl]-sulfonamide derivatives) inhibiting activating mutant EGFR and c-Met
kinases at various rates. Our scientific aim was to examine the anti-tumor potency and mechanism of action of
these selected inhibitors, and the newly synthetised analogues. Therefore we utilized clinically relevant NSCLC
cell lines (A549, H1975, HCC827, H1993) expressing c-Met and/or wild type or mutant EGFRs.
The newly synthetised sulfonamide analogues had remarkable IC50 values in vitro, one of them inhibited both
EGFR and c-Met enzymes in the submicromolar range. This inhibitor’s mechanism of action proved to be ATPcompetitive according to enzyme and in silico studies.
The sulfonamide analogues also suppressed the viability of the NSCLC cell lines used, and induced apoptosis
according to flow cytometry experiments. Western blot analyses showed that the compounds indeed inhibit the
phosphorilation of EGFR and c-Met kinases in the cancer cells. In this experiments the aforementioned EGFR –
c-Met dual inhibitor had effect on both EGFR and c-Met TKI sensitive cell lines.
Therefore we further characterised this promising compound’s drug-likeness with ADME studies (PAMPA and
CaCo-2 assays).
Acknowledgement: OM-00080/2008, and OM-00107/2008 grants, NKTH, Hungary.
Doctoral School: Pharmaceutical Sciences
Program: Modern trends in pharmaceutical sciences
Supervisor: Tibor Vántus
110
2012. április 12-13.
E/VII-5
ABSENCE OF CA2+-INDUCED MITOCHONDRIAL PERMEABILITY
TRANSITION BUT PRESENCE OF BONGKREKATE-SENSITIVE
NUCLEOTIDE EXCHANGE IN C. CRANGON AND P. SERRATUS
Department of Biochemistry, Semmelweis University, Budapest
Mitochondria from the embryos of brine shrimp (Artemia franciscana) do not undergo Ca2+-induced
permeability transition in the presence of a profound Ca2+ uptake capacity. Furthermore, this crustacean is the
only organism known to exhibit bongkrekate-insensitive mitochondrial adenine nucleotide exchange, prompting
the conjecture that refractoriness to bongkrekate and absence of Ca2+-induced permeability transition are
somehow related phenomena. Here we report that mitochondria isolated from two other crustaceans, brown
shrimp (Crangon crangon) and common prawn (Palaemon serratus) exhibited bongkrekate-sensitive
mitochondrial adenine nucleotide transport, but lacked a Ca2+-induced permeability transition. Ca2+ uptake
capacity was robust in the absence of adenine nucleotides in both crustaceans, unaffected by either bongkrekate
or cyclosporin A. Transmission electron microscopy images of Ca2+-loaded mitochondria showed needle-like
formations of electron-dense material strikingly similar to those observed in mitochondria from the
hepatopancreas of blue crab (Callinectes sapidus) and the embryos of Artemia franciscana. Alignment analysis of
the partial coding sequences of the adenine nucleotide translocase (ANT) expressed in Crangon crangon and
Palaemon serratus versus the complete sequence expressed in Artemia franciscana reappraised the possibility of
the 208-214 amino acid region for conferring sensitivity to bongkrekate. However, our findings suggest that the
ability to undergo Ca2+-induced mitochondrial permeability transition and the sensitivity of adenine nucleotide
translocase to bongkrekate are not necessarily related phenomena.
Supervisor: Christos Chinopoulos
111
E/VII-6
IKZF1 AND ARID5B GENE POLYMORPHISMS INFLUENCE THE
SUSCEPTIBILITY TO CHILDHOOD ACUTE LYMPHOID LEUKEMIA
Orsolya Lautner-Csorba1, Ágnes F. Semsei1, András Gézsi1, Nóra Kutszegi1, András Falus1,
Csaba Szalai2
1
2
Heim Pál Children’s Hospital, Budapest
Although childhood acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, its etiology
remains poorly understood. It has long been known that ALL have a genetic background elucidated through
association studies based on candidate genes that involved in transcriptional regulation and differentiation of
lymphocyte progenitors. ARID5B (AT-rich interactive domain 5B) is a novel susceptibility factor for childhood
ALL and plays a crucial role in the regulation of embryonic development, cell growth and differentiation. Ikaros
proteins (coded by IKZF1-Ikaros zinc finger 1 gene) are master regulators of lymphocyte development, and
differentiation. This study provides more detailed analysis to identify the causal variants of ARID5B and IKZF1
to susceptibility of childhood acute lymphoblastic leukemia.
We analysed the association of seven single nucleotide polymorphisms (SNPs) within the ARID5B and five
within the IKZF1 gene with the risk of ALL. In our study population 543 pediatric ALL and 529 healthy patients
were included. The genomic DNA was obtained retrospectively from whole, peripheral blood. Samples from
patients were taken in remission. Genotyping of the selected SNPs was carried out by Sequenom iPLEX Gold
MassARRAY technology (McGill University and Génome Québec Innovation Centre, Canada).
Based on our data we found that six polymorphisms influenced the risk of ALL significantly: rs11978267,
rs4132601, rs6964969 (IKZF1), rs10821936, rs4506592, rs7089424 (ADRI5B). The most relevant SNPs were:
rs10821936 (p=7.31*10-5; OR=1.430; 1.198-1.706) and rs6964969(p=1.67*10-5; OR=1.497; 1.246-1.800) in the
whole population and even in the subgroups of B-ALL and Hyperdiploid-ALL.
Our results contribute to the understanding of genetic basis of ALL development. Better elucidation of the
mechanisms through which ARID5B and IKZF1 variants are involved in childhood ALL could be of great
diagnostic value and help guide riskdirected therapy, ultimately improving disease management and outcome.
Program: Basic of human molecular genetics and gene diagnostics
Supervisor: Csaba Szalai
112
2012. április 12-13.
E/VII-7
INVESTIGATION OF THE MIRNA BINDING SITE POLYMORPHISMS
OF THE SNAP-25 GENE
As part of the SNARE complex SNAP-25 is a crucial protein of the central nervous system, its main function is
to catalyze the exocytosis of neurotransmitters. Animal models demonstrated that the pathological decrease of
SNAP-25 protein leads to hyperactivity and learning difficulties of the animals. Moreover the genetic
polymorphisms of the SNAP-25 gene were extensively analyzed as putative risk factors of neuropsychiatric
disorders including ADHD, schizophrenia and Alzheimer’s disease.
Aims: In this study we have performed an association study using real-time PCR technique to analyze the
possible association between the haplotype of two SNPs (rs3746544 and rs1051312) in the 3’ UTR region of the
SNAP-25 gene and impulsivity, which is a relevant endophenotype of the ADHD. In silico pilot analyses
suggested that the two SNPs may affect the binding sites of miRNA-641 and miRNA-510, consequently we have
also examined the functional role of this region by cloning the different 3’ UTR variants into luciferase reporter
system.
Results: The association analysis revealed, that people with the T–C haplotype achieved significantly higher
scores in the Barratt Impulsivity Scale compared to participants possessing G–T or T–T haplotypes (p = 0.013).
Interestingly the GC haplotype does not exist in our population.
Functional studies applying an in vitro cell culture with luciferase reporter system demonstrated that the miR641
bound to the 3’ UTR region of the SNAP-25 gene and decreased the amount of the generated protein. Moreover
both 3’ UTR SNPs (rs3746544 and rs1051312) altered the binding efficiency of miR641: the different haplotypes
of these two SNPs changed the binding site at 1 or 2 nucleotides resulting in a significant increase of protein
amount.
Supervisor: Zsolt Rónai
113
E/VII-8
REGULATION OF CASKIN1 SCAFFOLD PROTEIN BY EPHB1
TYROSINE KINASE
Szabolcs Pesti1, Annamária Balázs1, Beáta Szabó2, László Buday1,2
1
2
Institute of Enzymology, Research Centre of Natural Sciences, Hungarian Academy of Sciences,
Budapest
Scaffold proteins have an important role in the regulation of signal propagation. These proteins do not possess
any enzymatic activity but can contribute to the formation of multiprotein complexes. Although scaffold proteins
are present virtually in all cell types, the nervous system contain them in the largest amount.
Caskin proteins are typically present in neuronal cells, particularly, in the post synaptic density (PSD). Caskin1 is
able to form a complex with the Cask proteins; therefore it is referred to as Cask-interacting protein. By the
means of yeast two hybrid screening we have identified earlier a number of interacting protein partners of
Caskin1, including Abi2 and Nck adaptor proteins.
Here we demonstrated that EphB1 receptor tyrosine kinase can recruit Caskin1 through the adaptor protein Nck.
Upon activation of the receptor kinase, Nck SH2 domain binds to one of its tyrosine residues, while Nck SH3
domain interacts with the proline-rich domain of Caskin1. Complex formation of the receptor kinase, adaptor
and scaffolds proteins results in the tyrosine phosphorylation of Caskin1 on its SH3 domain. The
phosphorylation sites were identified by mass-spectrometry as tyrosines 296 and 336. To reveal the physiological
consequence of this phosphorylation, CD spectroscopy was performed. This measurement suggests that upon
tyrosine phosphorylation the structure of the Caskin1 SH3 domain changes dramatically.
Taken together, we show here that the scaffold protein Caskin1 can form a complex with the EphB1 tyrosine
kinase via the Nck protein as a linker. Translocation of Caskin1 to the plasma membrane leads to its tyrosine
phosphorylation on its SH3 domain. Although we were not able to identify any physiological partner of the SH3
domain so far, we could demonstrate that phosphorylation on conserved tyrosine residues results in marked
changes in the structure of the SH3 domain.
Supervisor: László Buday
114
2012. április 12-13.
E/VII-9
EFFECT OF EGCG ON MICROSOMAL CORTISOL PRODUCTION
Péter Szelényi
Cortisol, one of the most important stress hormones, is partly produced locally in the target cells from its
prohormone, cortisone. Cortisone reduction is catalysed by 11β-hydroxysteroid dehydrogenase type 1
(11βHSD1) in the endoplasmic reticulum (ER) lumen. The reductive power for this process is provided by
hexose-6-phosphate dehydrogenase (H6PD), which reduces luminal NADP+ to NADPH on the expense of
glucose-6-phosphate. The substrate enters the ER through a selective transporter (G6PT). Therefore,
cooperation of the “catalytic triad” composed of the three proteins mentioned above is necessary for the
activation of cortisol (Figure 1.). Increased pre-receptorial cortisol production likely plays an important role in the
metabolic syndrome and associated diseases, such as type 2
diabetes. Green tea flavanols have various health protecting
activities, including protection against obesity, the
metabolic syndrome and diabetes. These health effects are
mostly attributed to the major tea flavanol,
epigallocatechin-gallate (EGCG). The aim of the present
work was to reveal whether EGCG influences local cortisol
activation in the ER.
Microsomal vesicles were prepared from rat livers, and
cortisone-cortisol conversion was assessed by HPLC
measurements. EGCG efficiently inhibited cortisone
reduction in intact microsomes, so we examined the effect
Figure 1. Effect of EGCG to G6PT-H6PDHof EGCG on each component of G6PT-H6PDH11βHSD1 system
11βHSD1 system separately. Glucose-6-phosphate
transport was measured by rapid filtration. Direct cortisol-oxidizing activity 11βHSD1 was measured in
permeabilized microsomes by HPLC. The activities of H6PD and 11βHSD1 enzymes were determined by
fluorescent detection of NADPH.
Our results show that the primary target of EGCG is the luminal NADP-NADPH pool of the organelle rather
than the protein components of the catalytic triad. EGCG inhibits cortisol production through oxidation of
luminal NADPH in the ER. The observed phenomenon might play an important role in the anti-obesity and
anti-diabetic effect of green tea flavanols; and also reveals a novel potential drug-target for prevention and
therapy.
Supervisor: Miklós Csala
115
E/VII-10
SWITCHING ON RNA SILENCING SUPPRESSOR ACTIVITY BY
REMODELING THE ARGONAUTE BINDING DOMAIN
University of Szeged, Faculty of Medicine, Szeged
RNA silencing is a sequece specific RNA degradation mechanism that exists in almost all eukaryots. Among the
severeal functions of RNA silencing, it senses and degrades molecular envaders, such as viruses. Viruses evolved
silencing suppressors to overcome the effect of RNA silencing. Previous studies demonstrated that the P1
protein of Sweet potato mild mottle virus (SPMMV) inhibits the active RNA induced silencing complex (RISC)
by binding Argonaute, the catalytic component of RISC, via its three glicine-tryptophane (GW/WG) motifs.
We isolated the cDNA for the P1 protein of the Sweet potato feathery mottle virus (SPFMV). Sequence analysis
showed that SPFMV P1 is highly homologous to the SPMMV P1, mostly in the region, where the GW/WG
motifs are located in the SPMMV P1. However, SPFMV P1 contained only one GW/WG motif. Our functional
studies showed that SPFMV P1 did not have any silencing suppressor activity. Interestingly, remodeling the Ago
binding domain of SPFMV P1 by inserting two tryptophanes by in vitro mutagenesis resulted in gaining silencing
suppressor activity and Argonaute binding. To our knowledge, this is the first instance of turning a viral protein
of unknown function into a functional RNA silencing suppressor.
Doctoral School: Clinical Medicine, University of Szeged
Program: Immunology
Supervisor: Lóránt Lakatos
116
2012. április 12-13.
E/VIII
ORAL PRESENTATIONS
Chairperson:
Prof. Dr. Éva Szökő
117
118
2012. április 12-13.
E/VIII-1
INDICATION OF BRAIN PENETRABLE COMPOUNDS IN PLANT
EXTRACTS BY PAMPA-BBB – LC-MS ASSAY
Árpád Könczöl1, Ágnes Kéry2, Judit Müller1,3, Emília Földes3, György T. Balogh1
1
2
3
Compound Profiling Laboratory, Gedeon Richter Plc., Budapest
Department of Pharmacognosy, Semmelweis University, Budapest
Department of Organic Chemistry and Technology, Budapest University of Technology and
Economics, Budapest
Plant extracts with proven neurological bioactivity are attractive and potential targets for central nervous system
(CNS) drug discovery. In vast majority of cases, however, the molecular mechanism of action and the
constituents responsible for activity remain unclear or insecure due to the complexity of natural products. To
overcome this issue, predicting and evaluating the blood-brain barrier (BBB) permeability of natural products is
of key importance.
Parallel artificial membrane permeability assay (PAMPA) is a robust, 96-well plate based in vitro method for
assessing the rate of transcellular passive permeability of drug candidates through the blood-brain barrier. The
goal of our study was to validate the applicability of the PAMPA-BBB assay for identifying brain penetrable
compounds in really complex mixtures.
Our validation set contained 43 natural product drugs and natural
product-like drugs with experimental blood-brain partition coefficients (logBB=log(Cbrain/Cblood)) ranging evenly
from -2.0 to 1.0 in value. In order to measure the effective permeability (Pe) and membrane retention (MR%) of
each test compound, rapid liquid chromatography – mass spectrometry (LC-MS) methods were developed.
Finally, we demonstrate the applicability and advantages of PAMPA-BBB assay with the extract of Corydalis cava,
which contains several CNS active benzylisoquinoline alkaloids.
Supervisor: György Tibor Balogh
119
E/VIII-2
PHARMACOLOGICAL REGULATION OF TUMOR CELL ADHESION
AND MIGRATION BY CYTOTOXIC GNRH-III CONJUGATES AND RDEPRENYL DERIVATIVES TO PREVENT METASTASIS FORMATION
Eszter Lajkó1, Lívia Polgár1, Marilena Manea2, Gábor Mező3, Kálmán Magyar4, László Kőhidai1
1
2
3
4
Department of Genetics Cell- and Immunobiology, Semmelweis University, Budapest, Hungary
Department of Analytical Chemistry, University of Konstanz, Konstanz
Research Group of Peptide Chemistry, Eötvös Loránd University of Sciences, Hungarian
Department of Pharmacodynamics, Semmelweis University, Budapest
The impaired adhesion and the enhanced motility of tumor cells allow metastatic spreading of malignant cells.
Cancer cells possess characteristic features, including tumor specific expression of gonadotropin-releasing
hormone receptor (GnRH-R) and high level activity of monoamine oxidases (MAO), which are fundamental to
design specific therapies to prevent the disease or to slow down its progression.
In our present work the possible effects of antitumor drug-delivery GnRH-III conjugates and the MAO-B
inhibitor R-deprenyl and its derivatives were investigated on (i) cell adhesion, (ii) chemotaxis and (iii) proliferation
in order to elucidate their prospective significance as antimetastatic agents.
In our study conjugates of GnRH-III variants linked covalently to cytotoxic agents (Daunorubicin - Dau,
Doxorubicin - Dox) together with R-deprenyl, its metabolites and synthetic derivatives were tested. Adhesion of
MM6 monocytic model-cell was evaluated by impedance-based xCELLigence® technique. Chemotaxis was
measured by NeuroProbe® chamber. To analyse the antiproliferative effects CASY TT® system was used.
Our results demonstrated that GnRH-III(Dox) displayed the most notable cytotoxic effect after 72h. Significant
chemorepellent and adhesion inducer activities of GnRH-III(Dox) were also registered (10-8–10-6 M). The
Daunorubicin containing GnRH-III conjugates modified in position 4 by N-Me-Ser or Ac-Lys resulted in more
expressed antitumor and chemorepellent activity, increased adhesion compared to the referent GnRH-III(Dau).
The dimerization of the Daunorubicin containing monomers could decrease further the cell proliferation. Rdeprenyl at 10-6 M – effective for MAO-B inhibition – had chemorepellent character, enhanced adhesion and
exerted cytotoxicity in monocytes. The metabolite, R-amphetamine has retained the adhesion inducer and
chemorepellent characters on the most significant level. In respect of antiproliferative activity the presence of
para-fluoro group (p-fluoro-deprenyl) proved to be efficient.
In conclusion, simultaneous adhesion enhancer ability, chemorepellence and cytotoxicity of both GnRH-R and
the MAO-B targeted therapeutics enable them to prevent or slow down the formation of metastases of primary
tumors.
Program: Modern trends in pharmaceutical scientific research
120
2012. április 12-13.
E/VIII-3
IMPACT OF THE AQUATIC POLLUTANT HUMAN
PHARMACEUTICALS AND THEIR MIXTURES ON THE
PROLIFERATION AND MIGRATORY BEHAVIOR OF THE
FRESHWATER CILIATE TETRAHYMENA PYRIFORMIS
Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest
The assessment of the potential harmful effects to aquatic ecosystems or humans of the pharmaceuticals present
in water streams is a challenging task as it has to take into account the simultaneous action of a large number of
compounds. Because of the additive or synergistic combined effects considerable mixture toxicity may occur
even at individually not effective concentrations.
In the present work our aim was: (i) to screen the toxicity of 14 pharmaceuticals belonging to the most frequently
detected classes (anti-inflammatory and analgesic drugs, antibiotics, β-blockers and X-ray contrast media) to the
freshwater ciliate T. pyriformis; (ii) to describe the type of combined actions (additivity, synergism or antagonism)
of the 4 most toxic pharmaceuticals in their binary combinations; (iii) to study the influence of drugs on the
chemotaxis of Teterahymena at environmental concentrations.
Our results showed that the most potent pharmaceuticals were NSAIDs and β-blockers; the obtained EC50 values
(4.8 mg L-1 - 308.1 mg L-1) were comparable to algal or Daphnia bioassay data reported in literature. Antibiotics
and the contrast agent sodium-diatrizoate had no proliferation inhibiting effect. Chemotactic response of
Tetrahymena was more sensible than proliferation as significant chemorepellent action was observed in
environmental concentration for acetylsalicylic acid, diclofenac, fenoprofen, paracetamol, metoprolol,
propranolol, timolol and trimethoprim (Chemotaxis Index was 63% - 88%). Mixture toxicity experiments
resulted in a concentration dependent interaction type pattern with antagonism being the predominant
interaction type (59%) followed by additivity (37%) and synergism (4%).
In summary, our results underline the significance of Tetrahymena as a proper eukaryotic bioindicator of
environmental pollution since its proliferation and migratory behavior were finely and selectively modulated by
aquatic contaminant pharmaceuticals and their mixtures. However, to better understand the mechanisms
underlying the observed actions some specific biochemical endpoints (e.g. ATP consumption) should also be
investigated in the future.
121
E/VIII-4
DETERMINATION AND STUDY ON DOSE LINEARITY OF THE
PHARMACOKINETICS OF M-CHLOROPHENYLBIGUANIDE USING A
NEWLY DEVELOPED HPLC UV AND EC METHOD
Rudolf Laufer1,2, Péter Szegi2, Viola Csomor2, Kornélia Tekes2
1
2
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest
Introduction: meta-chlorophenylbiguanide (m-CPBG) is a HT3 receptor agonist. To investigate the
pharmacokinetic properties of m-CPBG a reliable validated bioanalitical method was developed. Serum,
cerebrospinal fluid (CSF) and eye samples were collected for pharmacokinetic analysis from Wistar rats after
different single dose (1, 3, 5, 10 µmol/200g) i.p. treatment. The animals were sacrificed after 20 minutes (n=5).
Methods: A JASCO HPLC-UV (Tokyo, Japan) system coupled with Intro electrochemical (EC) amperometric
detector (Antec Leyden, Netherland) was used for quantitative determination. The separation was done using an
Agilent Poroshell 120 EC-C18 narrow bore column (2.1 x 150 mm, 2.7 µm) with Agilent Zorbax Eclipse PlusC18 pre-column (2.1 x 12.5 mm, 5 µm). The mobile phase was 1:4 mixture of acetonitrile and citric acid –
sodium hydroxid buffer (pH=3). Octanesulfonic acid was used as ion-pairing agent. Quantitation of m-CPBG in
serum and eye samples was performed by UV detection. The sensitivity was not enough to measure low CSF
concentration. For this detection limit EC detection was investigated.
Results: We established a method which can be used for measurement of m-CPBG from different biological
samples. The LOQ was 25.6 pg and the LOD 7.7 pg on column respectively. The pharmacokinetics of m-CPBG
were found to be linear.
Program: Experimental and clinical pharmacology
Supervisor: Huba Kalász
122
2012. április 12-13.
E/VIII-5
TRIPODAL ION-BINDING RECEPTORS: SYNTHESIS AND
CHARACTERIZATION
Introduction: There is a considerable interest in small molecules with receptor-like ion-binding properties. In
2006, Tajc and Miller created a new pH-switchable molecule (1) by coupling tyrosine and cyclohexane 1,3,5trimethanol which has a closed conformation in the range of 9.2 < pH < 10.5 and can also serve as receptor in
aqueous solution at high pH either for various anions (e.g. Cl−, Br−) or cations (e.g. Zn2+, Cd2+) [1].
Aims: Based on their results [1] we decided to synthesize
HO
compound 1 and its mono- and dityrosine derivatives for thorough
characterization. We also aimed at designing other receptor
molecules with various ‘arms’ in order to study their protonation
and complexation behaviours.
H2N
Results: With some modification in the literature procedure [1]
trityrosine (1) and its tritryptophan and trihistidine analogues were
synthesized
in
a
straightforward
three-step
reduction/esterification/deprotection sequence from cyclohexane
1,3,5-tricarboxylic acid. As an unusual amino acid, p-aminophenylalanine was also coupled with cyclohexane 1,3,5-trimethanol.
The mono- and disubstituted derivatives of these four products
were also prepared. Protonation properties were investigated using
NMR-pH titration.
O
O
O
O
*3TFA
NH2
O
NH2
HO
O
OH
1
From cyclohexane 1,3,5-tricarboxylic acid as the carboxylic acid
component in the esterification reaction various esters and amides, including heterocyclic derivatives were also
produced. Utilizing the click reaction several triazol units were incorporated into new C3 symmetric systems.
All structures were characterized by NMR and HRMS experiments. Studies of their complexation properties are
in progress.
[1] Tajc, S. G.; Miller, B. L. J. Am. Chem. Soc. 2006, 128, 2532-2533.
Supervisor: Béla Noszál
123
E/VIII-6
PHARMACOKINETICS OF K203, A BIS-PYRIDINIUM MONOALDOXIME CHOLINESTERASE REACTIVATOR IN RATS AND
BEAGLE DOGS
Zita Pöstényi1, Péter Szegi2, Balázs Tasnádi1
1
2
Introduction: K203 is an experimental bis-pyridinium mono-aldoxime cholinesterase reactivator for potential
use in organophosphate/organophosphonate [OP] poisoning. Pharmacokinetics of K203 was examined in Wistar
rats and beagle dogs. Serum and cerebrospinal fluid concentrations of the oxime were determined using ion-pair
reversed-phase chromatography on octadecyl silica column.
Materials and methods: Male Wistar rats were injected with a single intramuscular (i.m.) dose of K203 freshly
dissolved in double-distilled water. The dose applied was 250 µmol/kg (114.5 mg/kg), five rats were treated in
each one of the seven groups, a group of rats was sacrificed after 5, 15, 30, 45, 60, 120 and 240 minutes
respectively. From the ether anesthetized rats blood was withdrawn and the serum was separated by
centrifugation (1600 g, 15 min, 4 0C). CSF was gained through the foramen occipitale magnum (90-140 µL).
Groups of two dogs (female and male) were treated with 15 µmol/kg (6.87 mg/kg) and 250 µmol/kg (114.5
mg/kg) K203 respectively. Biological samples were collected at 0 (before treatment) and 5, 10, 30, 60, 120 and
240 minutes following treatment. The whole brain samples were homogenized in four volume of 0.8 M
perchloric acid (PCA) at 20.000 rpm/min for 10 sec at room temperature. Aliquots of serum and CSF and
supernatants of brain homogenates were diluted with different amounts of 0.8 M perchloric acid. Precipitates
were removed using centrifugation at 14,000 g, at 4 °C, for 20 min.
Results: In rats the serum levels of K203 followed zero order pharmacokinetics from 15 to 120 minutes post
administration. Zero order pharmacokinetics was also observed in beagle dogs after low dose (15 µmol/kg) of
K203 administration. High dose administration (250 µmol/kg) led to subsequent hindered elimination from both
cerebrospinal fluid and serum.
O
NH2
+
N+
N
N
HO
2 Br-
1. ábra – The chemical structure of K203
Supervisor: Huba Kalász
124
2012. április 12-13.
E/VIII-7
OPTIMIZATION PROCESS AND HPLC BEHAVIOR OF SOME NOVEL
BIS-PYRIDINIUM ALDOXIMES
Péter Szegi1, Zita Pöstényi2, Balázs Tasnádi2, Rudolf Laufer1,2, Kamil Kuča3
1
2
3
University of Defence, Faculty of Military Health Sciences, Hradec Králové, Czech Republic
Introduction: Pyridinium aldoxims (PAs) are widely used for the treatment of organophosphate (OP) poisoned
persons. Antidote effect of PAs is based on the displacement of organophosphate moiety from the serine active
site. Kuca et al. have synthesized a series of novel compounds (K-compounds) to improve the therapeutic and
reactivating efficacy of oxime antidotes in OP poisoned subjects. The majority of these novel oximes are bispyridinium mono-aldoximes (BPAs) instead of the formerly preferred mono-pyridinium mono-aldoxime
(pralidoxime) or bis-pyridinium bis-aldoximes (obidoxime). These BPAs are polar, very hydrophilic compounds
having two positively charged quaternary nitrogen heteroatoms in pyridinium rings.
Our aim was to develop a new, validated RP-HPLC method to determine BPAs compounds from the different
biological samples.
Methods: A JASCO made HPLC system was used. The stationary phase was Zorbax RX-C18 octadecyl silica
column (4.6 x 250 mm, 5 µm). The mobile phase was 1,000 mL of buffer (10.03 g Na2HPO4·2H2O, 10.08 g citric
acid, 10 mg of EDTA-Na2·2H2O, pH adjusted to 3.7 with phosphoric acid), different type of ion-pairing agents
(IPAs) in various concentrations and 200 mL of acetonitrile. Migration characteristic (k’) versus IPAs was
checked in case of K-27, K-48 and K203 compounds. Each of these BPAs was eluted without any retardation by
the octadecyl silica stationary phase when 20% aqueous acetonitrile was used without any IPA. Employing an
IPA either octanesulfonic acid sodium or sodium laurylsulfate their retardation on this column can be arranged to
avoid any interference with the biological matrix peaks originated from serum, liquor, etc. Adequate monitoring
of the separated peaks of BPAs was possible in serum using ultraviolet absorbance (operated at 276 nm), and
using amperometric detection in brain and in cerebrospinal fluid (Eox = +0,8V).
Results: Our results showed that reversed-phase separation of various BPAs requires a certain concentration of
IPA. Alkyl sulfates or alkyl sulfonates with various chain lengths are preferably used, the retention depends on
the chain length of IPAs, and also on their concentration in the mobile phase. Adequate mobile phase is scouted
on the basis of retention of BPAs compared to the chromatogram of the background peaks originated from the
sample homogenate.
The newly developed HPLC mobile phases are significantly better to separate bis-pyridinium mono-aldoximes
from biological matrices than the formerly used ones.
Supervisor: Kornélia Tekes
125
E/VIII-8
CHARACTERIZATION OF OFLOXACIN-CYCLODEXTRIN
COMPLEXATION
Gergő Tóth1, Réka Mohácsi1, Ákos Rácz1, Aura Rusu2, Péter Horváth1, Szabolcs Béni1,
Béla Noszál1
1
2
University of Medicine and Pharmacy, Department of Pharmaceutical Chemistry, Targu Mures
Cyclodextrins are cyclic oligosaccharides capable to encapsulate molecules inside their apolar cavity forming noncovalent bonds and inclusion complexes of host-guest type. Ofloxacin is a racemic compound which belongs to
the fluoroquinolone class of chemotherapeutic agents with a broad spectrum of activity against Gram-positive
and Gram-negative bacteria. The effect of the S-(-) isomer is some 130 times superior of the R-(+)-isomer.
Cyclodextrin complexation of pharmaceutical compounds can result in improved properties of the guest in terms
of solubility, stability, protection against oxidation and light-induced reactions. Hence the investigation of
ofloxacin-cyclodextrin complexes is of critical importance to develop an ofloxacin formulation of improved
quality. Beside the enantioseparation, solubility and light-induced decomposition of ofloxacin can also be
beneficially modified by cyclodextrins. Despite the above advantages of cyclodextrins, no data can be found in
the literature on the systematic characterization of ofloxacin-cyclodextrin complexes regarding stability and
enantioseparation ability.
Aims: Our aim was to characterize various cyclodextrin inclusion complexes with ofloxacin enantiomers by
capillary electrophoresis, circular dichroism, molecular modeling, 1H NMR and 2D NMR (ROESY) techniques.
Results: By capillary electrophoresis the stability constants of 20 different ofloxacin-cyclodextrin complexes
were determined at two different pHs, where the average charge of ofloxacin was +1 and -1. The highest stability
as well as the highest enantioresolution was observed in the case of carboxymethyl-beta-cyclodextrin. Using
computational analysis we proved that the substitution pattern play an important role in the complex stability.
The complex stoichiometry and the geometric aspects of the inclusion complexes were studied by 1H and 2D
ROESY NMR, confirming that size of cavity highly influences the complex formation.
Program: Modern trends in phamaceutical scientific research
Supervisor: Béla Noszál
126
2012. április 12-13.
E/VIII-9
SAMPLE PRE-FRACTIONATION METHOD FOR ANALYSIS OF
GLYCOPROTEINS FROM HUMAN PLASMA
Hungarian Academy of Sciences, Research Centre for Natural Sciences, Budapest
Human plasma contains several glycoprotein biomarkers, but it has not yet been proved, that glycosylation
patterns changes are linked with the biomarkers’ prognostic properties. Therefore, study of glycoproteins is very
important. However, plasma is a complex biological system with different inorganic and organic compounds, and
it contains a wide range of proteins as well. Because of this complexity the determination of single protein
glycosylation patterns is quite difficult. To overcome this problem the proteomic analysis is usually preceded by
extensive sample preparation, and powerful sample pre-fractionation techniques need to be developed.
Aims: Our aims are to characterize glycosylation pattern of several plasma proteins. To achieve this goal, we
planned to develop an efficient plasma sample pre-fractionation method, starting from albumin and
immunoglobulin depleted plasma. Fractionation of remaining proteins should be solved by reversed phase
HPLC. In our case the use of reversed phase HPLC is mandatory, because it separates proteins with high
efficiency, but the different glycoforms of proteins elute together. This makes possible the analysis of
glycosylation pattern of the same protein from a single HPLC fraction.
Results: Our protein pre-fractionation method allows the analysis of several glycoproteins from plasma samples.
Applying this method we have successfully determined the glycosylation pattern of haptoglobin and alpha-1-acid
glycoprotein (AGP) originating from human plasma samples. AGP is a potential biomarker for diseases of the
cardiovascular system (e.g. atherosclerosis), but confirming this more clinical samples are needed.
We plan using the developed method for large-scale atherosclerosis study in cooperation with Semmelweis
University Heart Centre.
Supervisor: Károly Vékey
127
E/VIII-10
GLUCOSIDES OF MORPHINE CONGENERS: SYNTHESIS AND
CHARACTERIZATION
Morphine, the principal drug of the opioid family is among the most important agents used for the treatment of
pain. Morphine is primarily metabolized by microsomal enzymes in the liver of animals and humans through
dealkylation, hydrolysis, oxidation and conjugation. Some of the naturally occurring metabolites are
pharmacologically active, and thus contribute to the overall analgesic effect. Glucuronide and sulfate conjugates
of morphine and its congeners have long since been extensively studied; therefore their pharmacological
importance and physico-chemical properties are well described. Glucoside conjugates of xenobiotics are rarely
found in humans; however morphine C3 and C6 O-glucoside conjugates were recently identified in the urine of
cancer patients receiving oral morphine treatment. Since the physico-chemical attributes and the possible clinical
relevance of morphine glucosides have not been studied in detail, there is a need to synthesize glucosides
analogous to the identified naturally occurring metabolites.
Aims : This presentation focuses on the synthesis, HPLC separation and NMR spectroscopic analysis of C3 and
C6 O-glucoside conjugates of morphine congeners. Most of the reported compounds are novel chemical entities.
The presented data may serve as basis for pharmacological assays and a tool for the identification of glucoside
metabolites in biological samples.
Results : We synthesized a systematic series of O-glucoside ethers of morphine, codeine and their dihydroderivatives; mostly novel substances previously not reported in the literature. 6-O-glucosides were obtained by
the Koeigs-Knorr reaction, whereas 3-O-glucosides were synthesized by a novel method. The deacetylation
following glycosylation was carried out by hydrolysis with LiOH in methanol. Detailed 1H and 13C NMR
spectroscopy data and HPLC separation methods are presented that may be used as a reference for the
identification of glucoside conjugates in various biological samples.
Supervisor: András Gergely
128
2012. április 12-13.
E/VIII-11
CHARACTERIZATION THE EFFECTS OF A NOVEL PKD1 INHIBITOR
IN VEGF SIGNALING PATHWAY ON ENDOTHELIAL CELLS
Attila Varga1, Csaba Szántai-Kis2, Zoltán Horváth2, Zoltán Greff2, László Őrfi2,3, György Kéri1,2,
Tibor Vántus1
1
2
3
Vichem Chemie Research Ltd., Budapest
Protein kinase D1 (PKD1) is the member of a novel serine/threonine kinase family that includes PKD2 and
PKD3. In endothelial cells PKD1, as the member of the vascular endothelial growth factor receptor (VEGFR)
pathway, can be activated by the induction of VEGF and is able to modulate endothelial cell migration,
angiogenesis and inflammatory processes.
The aim of this study was to identify a novel PKD1 inhibitor and characterize its effects on endothelial cells
focusing on the role of PKD1 in VEGF signaling pathway.
We have identified a novel PKD1 inhibitor with nanomolar IC50 value by the screening of Vichem Ltd’s kinase
inhibitor library using biochemical IMAP® (Immobilized Metal Assay for Phosphochemicals) method. We
characterized the effects of the inhibitor on immortalized endothelial cell line EA.hy926. Treatment of the cell
culture with the inhibitor blocked the VEGF induced PKD1 activation and the phosphorylation of HDAC5,
which is the intracellular substrate of PKD1. The inhibitor arrested the VEGF induced endothelial cell migration
and it blocked effectively the endothelial cell tube formation. Moreover, we investigated the compound’s
potential cytotoxic effect, and it was well tolerated by the endothelial cells.
In summary, we characterized a novel PKD1 inhibitor which inhibits PKD1 activity in the angiogenic VEGF
signaling pathway and significantly reduces endothelial cell migration and tube formation.
Supervisor: Tibor Vántus
129
130
2012. április 12-13.
E/IX
ORAL PRESENTATIONS
Chairman:
Prof. Dr. László Kopper
131
132
2012. április 12-13.
E/IX-1
CHANGES OF miRNA EPRESSION PATTERN DURING THE HUMAN
MELANOMA PROGRESSION
II. Department of Pathology, Semmelweis University, Budapest
The death of human melanoma patients is almost invariably caused by metastases. Understanding the
pathomechanism of metastasis formation might provide a solid basis for new types of therapies that might be
more effective than the already existing ones. Evidently the miRNAs are involved in regulating many diverse
biological processes, and recent studies have indicated the differential expression of miRNAs between the
primary tumor and their metastasis. Our research group has created an experimental model in scid congenital
immunodeficient mice where we implanted a human melanoma cell line (HT199) semiortotopically(s.c.) into the
two types of animals: hosts with permissive and non-permissive metastatic microenvironment. In the first group
the melanoma formed lung metastases, however the metastatic progressionwas not detected at the same
localization int he secondgroup. The evaluation process involved creating primary cell cultures and then
miRNAsisolation from primary tumor cells, circulating tumor cells and (in the case of permissive group)
metastases from the same animals. The quantitative and qualitative changes of the miRNA expression during the
metastatic process as well as the differences between the permissive and non-permissive primary tumors were
evaluated by nCounter Human miRNA Expression Assay Kit (NanoString Technologies, Inc., Seattle, WA).
This kit measured the expression level (without amplification step) of more than 700 human and human-associated viral
miRNAs derived from miR Base. We were looking for the miRNAs of which expression was significantly different
(i.e. up or down regulated) in the circulating and the real lung metastasis derived in compare with subcutaneously
growing tumors’ expression pattern. We found 22 miRNAs consistently up-regulated (at least 2-fold difference)
in metastatic tumors along with primary tumors and 103miRNAs down-regulated in the same relation. This
experimental signature must be validated on formalin-fixed paraffin-embedded lung metastatic human skin
melanomas.
Program: Experimental oncology
Supervisor: Erzsébet Rásó
133
E/IX-2
ANGIOGENESIS IS CHALLENGED IN EXPERIMENTAL BRAIN
METASTASES
First Department of Pathology and Experimental Cancer Research, Semmelweis University,
Budapest
It is widely accepted that angiogenesis plays an important role in the maintenance of tumor growth. Tumors can
acquire their vasculature e.g. by vessel sprouting or inducing intussusceptive microvascular growth. These
processes require fibronectin and fibrin containing collagenous matrix. Since collagen I is absent in the brain
parenchyma with the exception of the wall of arteries, the significance of these types of angiogenesis during
vascularization of brain metastases is questionable.
In the present study our aim was to analyze the vascularization of experimental metastases following direct
injection of five different tumor lines to the brain parenchyma of mice. Morphometric analysis was performed on
methanol fixed frozen sections following various immunofluorescent labeling.
No angiogenesis was observed in the peritumoral zone of the lesions. The tumors acquired their vasculature
merely by incorporating the host vessels. Incorporated vessels retained their normal structure except that
astrocyte foot processes were replaced by the tumor cells. Tumors of epithelial origin showing pushing growth
pattern had lower vessel density and elevated vascular cell proliferation, compared to tumors showing invasive
growth. A process remarkably similar to intussusceptive angiogenesis was observed in the brain metastases of the
fibrosarcoma cell line. Tumor cells attached to the vessel caused the vessel lumen to split, and the pillars formed
were filled by tumor cells. However, branching angiogenesis was observed neither in the tumorous lesions nor in
the control cerebral wounds.
These data suggest that under experimental conditions no sprouting angiogenesis is needed for the incipient
growth of metastatic cerebral tumors. According to our observations metastases acquire their vasculature
exclusively by vessel incorporation in the mouse brain. This phenomenon may also be valid for small metastases
in the human brain. Under these conditions revision may needed considering the use of antiangiogenic agents.
Program: Oncology
Supervisor: Sándor Paku
134
2012. április 12-13.
E/IX-3
HEPATOCARCINOGENESIS IN MATRILIN-2 KNOCK OUT MICE
Alexandra Fullár1, Kornélia Baghy1, Ferenc Deák2, Bálint Péterfia1, Zsuzsa Schaff3, József Dudás4,
Ibolya Kiss2, Ilona Kovalszky1
1
2
3
4
Budapest
Insitute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged
Department of Otorhinolaryngology, Medical University Innsbruck, Innsbruck, Austria
Introduction: Matrilin-2 (Matn2) is a multidomain adaptor protein, which plays a role in the assembly of
extracellular matrix (ECM). It is produced by oval cells during stem cell-driven liver regeneration. The impact of
Matn2 on hepatocarcinogenesis was investigated in Matn2-/- mice comparing them with wild-type (WT) mice in a
diethylnitrosamine (DEN) -model.
Aim: The impact of Matn2 on hepatocarcinogenesis was investigated in Matn2-/- mice comparing them with wild-
type (WT) mice in a diethylnitrosamine (DEN) -model.
Methods: The liver tissue was studied macroscopically, histologically and immunohistochemically, gene
expression changes were investigated at mRNA level by real-time PCR, at protein level by macro array and
Western blot.
Results: Matn2-/- mice exhibited higher susceptibility for hepatocarcinogenesis compared to wild-type (WT) mice.
In their liver spontaneous microscopic tumor foci developed. After DEN treatment the liver of Matn2-/- mice
contained visible tumors larger both in number and size than that in WT liver. Differing from WT liver
spontaneous phophorylation of EGFR, p44/42 (ERK1/2), GSK-3α/β and retinoblastoma protein (p-Rb),
decrease in p21/CIP1 level and increase in β-catenin protein expression was detected. Focal Ki-67 positivity of
these samples provided further support for our presumption, that the lack of Matn2 set the livers into a proproliferatory state, making them prone for tumor development. This enhanced proliferative capacity was further
increased in the tumor nodules of DEN-treated Matn2-/- livers.
Conclusion: Our study suggests that Matn2 functions as a tumor suppressor in hepatocarcinogenesis, and in this
process EGFR activation together with that of ERK1/2 as well as inactivation of GSK-3β are playing strategic
role.
Program: Oncology
Supervisor: Ilona Kovalszky
135
E/IX-4
ONCOGENIC MUTATION DEPENDENT EFFECT OF PRENYLATION
INHIBITION IN MELANOMA CELLS
Tamás Garay1, István Kenessey1, Éva Juhász1, Andrea Réti1, Viktória László2, Judit Dobos3,
Violetta Piurkó1, Walter Berger4, József Tóvári3, József Tímár1, Balázs Hegedűs1
1
2
3
4
Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
Deptartment of Tumor Progression, National Institute of Oncology, Budapest
Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Vienna,
Austria
Background: Malignant melanoma has one of the worst prognoses among solid tumors and is still a major
therapeutic challenge. In the majority of cases oncogenic mutations of BRAF or NRAS drive tumour growth and
are attractive molecular therapeutic targets. Accordingly, we investigate the response of NRAS or BRAF mutant
as well as double wild-type human melanoma cells to prenylation inhibition by zoledronic acid.
Materials and methods: Cell viability and chemotactic migration was assessed with SRB colorimetry and transwell migration assay. Cell motility and proliferation were determined via videomicroscopy. Tumor growth and
development of metastases were examined in NSG mice subcutan xenograft and in the spleen liver colonization
model in vivo. Activation of the signaling pathways was quantified by immunoblot analysis of the phosphorylation
of Erk1/2 and S6 proteins.
Results: Zoledronic acid treatment decreased cell viability and cell proliferation in a dose dependent manner in
all melanoma cell lines investigated in vitro. NRAS mutant and double wild type cells showed no response to
prenylation inhibition in migration. Of note, trans-well migration was inhibited though haptotactic migration was
increased after zoledronic acid treatment in BRAF mutant cells parallel with an increased level of Erk1/2
activation. No significant decrease in primary tumor growth in subcutan xenografts in NSG mice was found. Of
note a modest decrease in metastatic potential in spleen-liver colonization experiment with BRAF but not with
NRAS mutant human melanoma cells was measured. In contrast, the lower dose of zoledronic acid treatment
resulted in a significantly higher metastasis formation in double wild type cells.
Conclusions: Altogether our data demonstrates that the underlying oncogenic alterations are critical in
determining the sensitivity of melanoma cells to molecular targeted treatment modalities. Furthermore our
findings demonstrate that targeting signaling pathways that are not upregulated in a certain tumor may have
adverse effects on tumor progression.
This work was supported by National Science Found (CNK-77649, MOB-80325) and TÁMOP.4.2.1.B-09/1/KMR-20100001.
Program: Oncology
Supervisor: József Tímár
136
2012. április 12-13.
E/IX-5
GENETIC AND EPIGENETIC EXAMINATION OF THE SMARCB1/INI1
GENE IN EPITHELIOID SARCOMA
Gergő Papp
Budapest
Introduction : Damages of the INI1 gene on chromosome 22 has been known for a long while but its molecular
background was mapped recently. Loss of SMARCB1/INI1 protein expression has been reported in many tumor
types but the highest percentage of INI1 negative cases are probably malignant rhabdoid tumors and epithelioid
sarcomas. The INI1 inactivation in rhabdoid tumors is associated with genetic alterations as biallelic deletion
and/or mutation, while some other soft tissue tumors such as epithelioid sarcoma, despite the INI1 negativity,
there is still no genetic aberration. All of the rescent evidences suggest that epigenetic mechanisms are involved in
the loss of INI1 expression.
Aims : We examined the 22q11.2 chromosomal region by FISH of 31 INI1 negative cases and performed direct
sequencing of the gene nine exons. In the remaining 25 cases without genetic alterations the methylation status
of the INI1 promoter region was examined by using methylation sensitive PCR. We assumed hypermethylation
could account for the decreased expression of the protein. To determine the mRNA expression of INI1, RTPCR was performed, in order to avoid the interference of the stroma cells, laser capture microdissection (LCM)
was also carried out.
Results : Analysis of 31 epitheliod sarcoma cases with loss of protein expression revealed 6 cases with INI1 gene
alterations at the DNA level (homozygous deletion, 4; deletion of one allele and mutation of the other, 2) that
could have induced the loss of gene products. None of the genetically intact tumors demonstrated methylation of
the INI1 promoter region. By RT-PCR complete down-regulation of INI1 mRNA was clearly shown in the
tumor cells. Investigation the EZH2 protein expression, it seems not the histone methylation but microRNA
inhibition may play a role in the INI1 inactivation in epithelioid sarcomas.
Program: Oncology
Supervisor: Zoltán Sápi
137
E/IX-6
EXAMINATION OF TARGETED SNP VARIANTS IN SIX GENES WITH
POSSIBLE EFFECT ON ADULT CRANIAL SUTURE SYNOSTOSIS
Katalin Wolff1, Zoltán Vas2,3, Éva Hadadi4
1
2
3
4
Department of Forensic and Insurance Medicine, Semmelweis University, Budapest
Department of Biomathematics and Informatics, Faculty of Veterinary Sciences, Szent István
Hungarian Natural History Museum, Budapest
Introduction: The elements of the cranial vault are purely membranous bones, separated by connective tissue
sutures which usually stay open till the adulthood. Premature fusion of cranial sutures, known as
craniosynostosis, presumably involves disturbances in the developmental signalling pathways. What is lesserknown, whether similar processes influence the obliteration pattern in adulthood or not.
Some age estimation methods suppose that from the degree of suture obliteration the actual age of the person at
death can be estimated. According to our previous results, no close correlation was found between the extent of
obliteration and chronological age. These experiences suggest that cranial suture closure in adults is a more
complex process and it can be strongly influenced not only by the age, but other environmental effects and
genetic background as well. Our goal was to examine and determine some single nucleotid polimorfisms in
targeted molecules, which might have an effect on cranial suture closure in adults.
Materials and methods: Ossification of cranial sutures was ascertained, and peripheral blood samples were
collected during autopsy procedure of 106 individuals. Genomic DNA was isolated at the DNA Laboratory of
the Department of Forensic and Insurance Medicine, Semmelweis University. Genotyping of SNPs was
conducted using competitive allele-specific PCR KASPar chemistry (KBiosciences Ltd, Hertfordshire, UK)
according to the manufacturer’s instructions. Statistical analyses were undertaken using R software.
Results and conclusion: According to our preliminary results MSX1: rs3821947, and to a lesser extent BMP4:
rs2761887 showed significant association with the degree of cranial suture closure in adults. Both MSX1 and
BMP4 play an important role in calvarial bone development and they have a possible effect on sutural
mesenchyme in latter postnatal stages. Despite the absence of any former, similar experiences, our observation
suggests that further examinations are required to explore the causal mechanism of suture synostosis.
Program: Public health and health sciences
Supervisor: Péter Sótonyi
138
2012. április 12-13.
E/IX-7
ANTIVIRAL EFFECTS OF A FERMENTED WHEAT GERM EXTRACT
(AVEMAR), IN THE FELINE AIDS MODEL
Balázs Stercz
Department of Medical Microbiology, Semmelweis University, Budapest
Avemar, an FDA-approved supplement for cancerous patients, stimulates cellular immunity, improves
hematological parameters, elicits apoptosis of malignant cells, hinders autoimmune reactions. These suggest that
Avemar might inhibit human/animal immunosuppressive viruses.
Aims: To study in vitro the inhibitory effect of Avemar on the etiological agent (feline immunodeficiency virus,
FIV) and its transactivating cofactor (feline adenovirus, FeADV) in the feline AIDS model.
Methods: Feline lymphoid (MBM) and kidney (CrFK) cell cultures were infected with the American (FIV-Pet)
and European (FIV-Pisa/M2) isolates of FIV and maintained as with FL-4 lymphoid cells producing FIV
continuously. Human cervical cancer cell line (HeLa) and CrFK cells were infected with FeAdV. Infected and
uninfected cells were treated with a serial dilution of Avemar, subsequently its toxicity (fotometric assay), as well
as viral cytopathic effect and virus load (p24 antigen ELISA) were monitored.
Results: Up to 2000 microg/mL Avemar is not toxic to feline cells. In a dose-dependent manner it augments
MBM growth, does not affect CrFK but slightly inhibits HeLa growth. Avemar induces apoptosis and declination
of FIV-Pet production of FL-4 cultures. A single Avemar dose inhibits both apoptosis and FIV production by
MBM cells for 17 days. FIV-Pisa/M2 is more sensitive. A single Avemar dose also inhibits FeAdV production by
CrFK cells for 6 days with accelerated cell death. FeAdV replication in Hela cultures is inhibited for 3 days only.
Inhibitory effect depends on the cell line origin of FeAdV. In simultaneous infections, precedent FIV infection
decreases FeAdV replication.
Conclusions: Avemar exerts different effects on uninfected and infected cells. It decreases both FIV and FeAdV
producing capacity. Facilitating cell death of chronically infected cells is advantageous. Suppression of virus
production, but maintenance of cell integrity in an acute infection is protective. In humans and cats Avemar
might contribute to viral load suppression and immune restoration.
Program: Alterations of cells, fibres and extracellular matrix. Diagnosztic pathomorphological studies int he
course of heart and vascular diseases and incertain tumours. Experimentsl and diagnostic
pathomorphological studies
Supervisor: József Ongrádi
139
E/IX-8
mTORC1 AND C2 EXPRESSION IN HUMAN COLON CANCER
Tamás Sticz, Anna Sebestyén, Ágnes Márk, Melinda Hajdu, Tamás Micsik, Noémi Nagy,
László Kopper
Budapest
Several signaling pathway defects are well known and characteristic in the development of colon carcinoma.
Mutation and overactivation of the EGFR pathway is an important new target in its therapy. However, 40% of
patients do not respond to EGFR inhibitor therapy. One possible reason for EGFR inhibitor resistance may be
the increased activity of the PI3K/PTEN/Akt/mTOR pathway. Studies show that mTOR expression is
increased in approximately 60% of colorectal cancers. mTOR appears in two different complexes (mTORC1 and
C2) with potentially different mTOR inhibitor sensitivity. Data is limited about the expression of mTORC1/C2
in colon cancer and its therapeutic and prognostic benefit. We studied the expression of mTOR activity and the
expression of the two different complexes in human colon carcinoma biopsies.
Tissue microarray blocks were constructed from 82 colorectal adenocarcinoma biopsies. Immunohistochemical
results of p-S6, p-mTOR, Rictor (mTORC2 characteristic protein) and Raptor (mTORC1 characteristic protein)
staining were evaluated and compared to clinical and survival data.
We show that colon carcinoma cells have notable mTOR activity. Moreover, 95.1% of the tumors showed Rictor
and/or Raptor mTOR complex protein expression. 87.8% of the tumors expressed Rictor. Dominant expression
of Raptor was present in 17%, but dominant Rictor expression was more frequent: 37.8%. Rictor overexpression
and mTORC2 complex dominancy in more than 1/3 of patients raises the possibility of rapamycin analog
insensitivity. We also found that mTOR activity and dominant expression of Rictor was associated with worse 4year survival (OS 55.8%), whereas mTORC1 related mTOR activity or low mTOR activity correlated with better
prognosis (OS 98%).
These results suggest that rapalogs or dual mTORC1/2 inhibitors could be additional drugs in the targeted
therapy of colon carcinomas, however, patient and inhibitor selection criteria should be carefully considered.
Supported by OTKA 84262, ETT 105/2009
Program: Oncology
Supervisor: László Kopper
140
2012. április 12-13.
E/IX-9
CONNECTIONAL HIERARCHY IN THE PRIMARY SOMATOSENSORY
CORTEX OF PRIMATES
Maria Ashaber1, Emese Pálfi1, Cory Palmer2, Orsolya Kantor1, Robert M. Friedman4, Anna W.
Roe4, Laszlo Négyessy1,3
1
2
3
4
Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest
Department of Mathematics, University of Illinois, Urbana, USA
Wigner Research Centre for Physics, Hungarian Academy of Sciences
Department of Psychology, Vanderbilt University, Nashville, USA
Primary somatosensory cortical area 3b (A3b) and adjacent area 1 (A1) exhibit similar functional organizations.
However, it is thought that area 1 represents a higher processing stage than area 3b. The somatotopic
representations of the two areas are not equivalent: cortical magnification factors and neuronal receptive field
properties are different. We studied underlying connectional properties of the functional hierarchical relationship
of A3b and A1. These questions were investigated by the combination of electrophysiological and bidirectional
neuronal tract tracing methods in the primary somatosensory cortex focusing on A3b and A1, of the squirrel
monkey. Laminar distribution of retrograde and anterograde labeling, which were mostly localized to the
superficial layers, did not reveal specific hierarchical relationship between the two areas. Anisotropy index,
computed for the intrinsic connections indicated a mediolaterally oriented distribution suggesting strong crossdigit connectivity within the areas. Intrinsic connections of area 1 were spatially more extensive than that of A3b,
which support widespread integration between fingertip representations in A1. Notably, the distribution of
intrinsic connections in A3b was modular exhibiting several peaks of densities, while in A1 the density of
intrinsic connections peaked around the site of injection and gradually decreased with increasing distance from
the injection site. This observation suggest that modular organization is more prevalent in A3b then in A1. The
size of the region with the strongest retrograde labeling in A1 tended to be smaller than that found in A3b.
However, consistent with previous studies on cortical magnification factor, the size of skin areas represented by
these heavily labeled cortical fields was similar or greater in A1 than in A3b. This finding supports previous
observations suggesting a larger convergence of somatosensory information on neurons of area 1 as compared to
that of 3b.
Supported by FIRCA NS059061, OTKA NN79366 and NIH NS044375.
Program: Neuromorphology and cell biology
Supervisor: László Néggyesi
141
E/IX-10
LAMINAR ANALYSIS OF THE SLOW CORTICAL RHYTHM IN RAT
SOMATOSENSORY CORTEX UNDER KETAMINE/XYLAZINE
ANESTHESIA
Richárd Fiáth1, Bálint Péter Kerekes1, György Karmos1,2, István Ulbert1,2
1
2
Institute of Cognitive Neuroscience and Psychology, Research Centre for Natural Sciences,
Hungarian Academy of Sciences, Budapest
Faculty of Information Technology, Pázmány Péter Catholic University, Budapest
The slow cortical rhythm (SCR) emerges during the deepest stage of non-rapid eye movement (NREM) and is
present over the whole cortical mantle. The cellular counterpart of the SCR, the slow oscillation is characterized
by rhythmic alternation of two phases: the “up-state” with strong synaptic activity, cell discharging and
depolarized membrane potential and the hyperpolarized “down-state” with neuronal silence. Ketamine/xylazine
(KX) is a commonly used anesthetic cocktail to model the natural SCR. Under KX narcosis a stable and
continuous slow oscillation can be recorded from all cortical regions. The exact mechanisms underlying the SCR
are still unclear, however, recent evidence suggest that in humans it is mainly generated in the supragranular
layers.
To compare human results to animal data, we recorded the electrical activity from the trunk region of the rat
somatosensory cortex with 24-contact laminar silicon multielectrodes during KX narcosis. The wideband
recordings (0.1-7000Hz) were separated into local field potential (LFP, 0.1-500Hz) and multiple-unit activity
(MUA, 500-5000Hz). To estimate the position and magnitude of current sources and sinks in different layers of
the cortex near the recording electrode we also calculated the current-source density.
During the up-states strong inward synaptic/trans-membrane currents were observed in the supragranular and
granular layers. This sink was surrounded by two current sources, one located mostly in layer I, the another in the
infragranular layers. This source-sink-source pattern was reversed during the down-states. Up-state locked
averages showed the strongest MUA in layer V where the soma of giant pyramidal cells are located. Our results
suggest that the generator mechanism of SCR in rodents is partially similar to that of humans, since the most
impressive current sink is located superficially in both cases. However, the existence of substantial outward
currents in deep layers and the infragranular MUA maximum may reveal possible differences between the two
conditions.
Supervisor: István Ulbert
142
2012. április 12-13.
E/IX-11
CENTRAL AMYLIN IS A NOVEL NEUROPEPTIDE WITH POTENTIAL
MATERNAL FUNCTIONS IN RAT
Neuromorphological and Neuroendocrine Research Laboratory, Department of Anatomy,
Histology and Embryology, Hungarian Academy of Sciences and Semmelweis University,
Budapest
Amylin, a peptide previously known to be released from the pancreas, was found to be expressed in the preoptic
area of mother rats in our recent microarray study. Here, we report that amylin is not expressed in the brain
during pregnancy but a significant increase in amylin expression is found immediately after parturition in the
preoptic area, a region whose lesion abolishes maternal behaviors. We also showed that amylin mRNA level
remained elevated as long as the pups were not removed from the dams. Amylin expression was also induced in
virgin but maternally behaving (sensitized) non-lactating but not in non-sensitized virgin females or in females
who did not become maternal despite the sensitization procedure. Immunohistochemistry verified the increased
amylin peptide expression in maternally behaving rats and demonstrated the same expression pattern of amylin in
dams as in situ hybridization histochemistry. Ovariectomy had no effect on the activation of amylin neurons
suggesting sexual steroid independent mechanisms. In subsequent experiments, mothers were separated from
their pups for 22 hours. Upon returning the pups, neuronal activation was found in the mothers´ preoptic area
with a distribution pattern similar to amylin-expressing neurons situated in the medial preoptic nucleus, parts of
the medial preotic area, and the ventral part of the bed nucleus of the stria terminalis. Double labeling revealed
that 86-93% of amylin neurons were activated by pup exposure. The results implicate that amylin is a novel
neuropeptide with specific maternal functions possibly exerting its actions on maternal behaviors via amylin
receptors known to be present in brain regions to which preoptic neurons project.
Support: Bolyai János Fellowship of the HAS, OTKA NNF2 85612 and K100319 research grants.
Supervisor: Árpád Dobolyi
143
144
2012. április 12-13.
P/I
POSTER PRESENTATIONS
Chairman:
Dr. Barna Vásárhelyi
145
146
2012. április 12-13.
P/I-1
EXAMINATION OF PHOTOSENSITIZER-CELLULAR MEMBRANE
MODEL WITH OPTICAL SPECTROSCOPY METHODS
Application of porphyrins as photosensitizers (PS) is based on their light-triggered generation of reactive oxygen
species (ROS) that may cause oxidative damages and ultimately kill cells. Cellular membranes are the action
grounds of many sensitizers due to their amphiphilic character as well as the location of many of the targets
attacked by ROS. Hence, the binding ability and location of porphyrins in liposomes as simple models of cellular
membranes are of outstanding interest. Here we compare two similar mesoporphyrin (MP) derivatives, namely,
MP IX dimethyl ester (MPE) and MP IX dihydrochloride (MPCl).
Goals: Monocomponent small unilamellar vesicles formed of different phosphatidylcholines with incorporated
MPs were investigated. We determined the binding parameters by conventional spectroscopy and the
inhomogeneous distribution functions (IDFs) by ﬂuorescence line narrowing (FLN) spectroscopy. The generated
ROS of the porphyrins form triiodide (I3+) in the presence of potassium-iodide (KI) and molybdate (MoO4). The
generation of triiodide was measured with absorption spectroscopy.
Results: We found that the binding ability of MPE is considerably higher than that of MPCl. IDFs show three
distinct binding sites. Based on a consistent interpretation at the molecular level the “site I” is between the two
lipid layers (for MPE), “site II” is deeply between the hydrocarbon chains (for both) and “site III” is between the
head groups (for MPCl). The generation of triiodide was similar in the presence of phosphatidylcholines and
different without phosphatidylcholines.
Supervisor: Levente Herényi
147
P/I-2
RED BLOOD CELL DISTRIBUTION WIDTH PREDICTS
UNFAVOURABLE OUTCOME FOLLOWING CARDIAC
RESYNCHRONIZATION THERAPY
Annamaria Kosztin1, Gabor Szeplaki1, Eszter Maria Vegh1, Szabolcs Szilagyi1, Istvan Osztheimer1,
Levente Molnar1, Endre Zima1, Laszlo Geller1, Zoltan Prohaszka2, Bela Merkely1
1
2
3rd Department of Internal Medicine, Semmelweis University, Budapest
Cardiac resynchronization (CRT) therapy is a useful method in the treatment of severe heart failure patients
refractory to optimal medical therapy with intraventricular conduction delay. While heart failure as a systemic
disease also affects the circulation and function of bone marrow and kidneys, previous studies have shown some
haematologic parameters and renal function parameters could be promising markers for the prediction of heart
failure progression. Our aim was to determine the possible predictive value of these factors on the clinical
outcome following CRT.
We included 147 patients with wide QRS (>=120 ms) and NYHA II-IV class severe heart failure, who
underwent CRT in our prospective study. Routine hematologic parameters, renal function and B-type natriuretic
peptide (NT-pro-BNP) were determined preoperatively. Primary endpoint was cardiovascular mortality or heart
transplantation; secondary endpoint was responder state at 6 months following CRT implantation. Patients who
improved at least one class on the NYHA state or improved at least 10% on the 6 minutes walking distance were
considered as clinical responders.
Those patients who met the primary end point had significantly higher NT-pro-BNP (3000 (1829-3000) vs. 1978
(1829-3000) pg/ml, p=0.028), glomerular filtration rate (GFR; 68.3 (47.7-87.1) vs. 56.1 (34.4-62.1)
ml/min/1.73m2, p= 0.035) and creatinine (118 (109-144) vs. 98 (79-134) μmol/l, p=0.029) compared with the
remaining patients .
We also found significant difference in red blood cell distribution width (RDW) between the two groups (RDW
14.2 (13.6-15.2) vs. 13.4 (12.9-14.2)%, p=0.004). No significant difference was found in red blood cell count,
hemoglobin, hematocrite, MCV, MCH or MCHC.
We found an increased risk for mortality or heart transplantation in patients with high baseline RDW (odds ratio
3.5, 95% confidence interval: 1.2-10.7, p=0.038). High baseline RDW also predicted the combined end point
(mortality, heart transplantation or non-responder state) at an odds ratio of 2.4 (95% confidence interval: 1.1-5.4,
p=0.036). NT-pro-BNP (p=0.101), GFR (p=0.217) or creatinine (p=0.228) did not have significant predictive
values.
Based on our results, the gold standard marker NT-pro-BNP or renal function was not able to predict the
outcome in this clinical setting. RDW seems to be a promising marker for the prediction of clinical outcome
following CRT.
Grants: TÁMOP-4.2.2./B10/1.-2010-0013; TÁMOP-4.2.2-08/1/KMR-2008-0004.
148
2012. április 12-13.
P/I-3
THE EFFECT OF OBESTATIN ON BEHAVIORAL RESPONSES
INDUCED BY MORPHINE WITHDRAWAL IN MICE
Nándor Lipták1, Roberta Dochnal2, Krisztina Csabafi1, Júlia Szakács1, Gyula Szabó1
1
2
Institute of Pathophysiology, Faculty of Medicine, University of Szeged, Szeged
Department of Child and Adolescent Psychiatry, Faculty of Medicine, University of Szeged,
Szeged
The goal of this study was to examine the effect of obestatin on morphine withdrawal-induced behavioral
responses in mice. Obestatin is a peptide hormone derived from precursor preproghrelin. The behavioral effects
of obestatin have not been clarified yet.
The open-field (OP) and elevated plus maze (EPM) tests were used to assess morphine withdrawal-induced
exploratory behavior changes. In our experiments CFLP male mice were treated twice a day with graded doses of
morphine (day 1: 10 mg/kg, day 2: 20 mg/kg, day 3: 40 mg/kg; s.c.) or saline and once a day with obestatin (0.8
μg or 1.5 μg/2 μl, i.c.v., respectively) or artificial cerebrospinal fluid for 3 days. On day 4, naloxone (0.2 mg/kg,
s.c) or saline was administered 2 h after the final injection of morphine at a dose of 20 mg/kg, and the behavioral
changes were measured 5 min after the naloxone injection. Obestatin was administered 15 min before
assessment. The following behavioral parameter was monitored in the OP: the percentage of time spent in the
center; whereas in the EPM: the time spent in open arms and the entries into open arms compared to the total
time and entries.
The higher dose of obestatin significantly decreased the percentage of time spent in the center in the OP. The
lower dose of obestatin increased this parameter, but the difference was not significant compared to the mice in
morphine withdrawal. EPM results were similar to open field, but neither the lower dose, nor the higher dose of
obestatin had a significant effect on the ratio between the open arm time and total time.
In our study we confirmed in two different methods that obestatin has dose-dependent effect on exploratory
behavior induced by morphine withdrawal. These data suggest that obestatin may have a role in behavioral
responses induced by morphine withdrawal.
This study was supported by ETT 355-08/2009 and TÁMOP 4.2.1./B-09/KONV-2010-0005.
Doctoral School: Theoretical Medicine, University of Szeged
Program: Psysiological and pathological functions of the neuroendocrine system
Supervisor: Gyula Szabó
149
P/I-4
ELASTIC, CONTRACTILE AND ENDOTHELIAL PROPERTIES OF
HUMAN VEIN SEGMENTS STORED IN A COMPLEX TISSUE MEDIUM
Anna Monori-Kiss1, Gábor Ferenc Molnár2,4, Attila Nemes2, Violetta Kékesi3, Emil Monos1, György
László Nádasy1
1
2
3
4
Institute of Clinical Experimental Research and Human Physiology, Semmelweis University,
Budapest
Department of Vascular Surgery, Semmelweis University, Budapest
Department of Cardiology, Semmelweis University, Budapest
Länsjukhuset Halland, Halmstad, Sweden
Many types of arterial bypass operations use freshly removed or stored vein segments as autotransplants. We
wanted to answer two questions: how do the passive and active biomechanical properties alter during the storage
in different ways? Does storage in complex tissue medium (TCM) yield some advantage over more simple storage
forms? The saphenous vein samples were collected routinely from patients scheduled for coronary bypass
operations. We collected 72 venous segments from 32 patients, and randomly distributed them to 8 groups: fresh
veins those tested immediately, segments stored in normal Krebs-Ringer solutions for 1 and 2 weeks, at 0-4°C,
segments stored in TCM for 1, 2, 3 and 4 weeks also at 0-4°C, and cryopreserved segments stored at -140°C for a
few weeks. After the storage, we made biomechanical tests with a pressure microangiometer. We determined the
incremental distensibility and incremental elastic modulus, the contractility and the endothelial dilation of the
segments. We found that segments stored in nKR solution dilated morphologically, lost their ability to contract,
and their distensibility decreased in one week. However the segments that were stored in TCM preserved their
contractility for one week. Wall thickness slightly decreased, but without affecting the lumen diameter. The elastic
parameters were almost identical to those of fresh segments. Cryopreserved veins narrowed morphologically,
their wall thickened, and their contractility diminished. In conclusion, we tested some common technics applied
for storage of human saphenous vein segments. Storage in TCM preserves the contractility and smooth-muscle
function up to 4 weeks, with no change in elastic properties. The maintained contractility and elasticity of those
segments can be expected to improve the veins’ transplant survival and patency when grafted in vivo. (OTKA
TO32019, OTKA TO42670, Hungarian Kidney Foundation, GFM obtained a grant as a PhD student from the
Ministry of Education, Hungary)
Supervisor: György Nádasdy, Emil Monos
150
2012. április 12-13.
P/I-5
COMPARISON OF EPITAXIALLY AND SOLUTION-GROWN AMYLOID
ß25-35 FIBRILS
Ünige Murvai1, Judit Somkuti1, Katalin Soós2, Botond Penke3, László Smeller1,
Miklós S. Z. Kellermayer1
1
2
3
Department of Medical Chemistry, University of Szeged
Supramolecular and Nanostructured Materials Research Group of the Hungarian Academy of
Sciences, Szeged
Amyloid fibrils play a key role in a wide range of protein misfolding disorders. Amyloid ß peptides form selfassociating fibrillar structures in Alzheimer's disease. The biologically active, toxic fragment of the full-length beta
peptide, the Aß25-35 peptide is able to form an oriented network on mica by an epitaxial assembly mechanism.
Whether the structure of the epitaxially grown fibrils is similar or identical to that of the fibrils assembled under
equilibrium conditions is not known. To explore these differences, we investigated fibril structure and dynamics
with atomic force microscopy, force spectroscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy
methods.
According to our AFM experiments the epitaxially-grown fibrils were significantly different from solution-grown
fibrils in terms of their morphology and formation kinetics. The fibril height was 1-3 nm for the epitaxiallygrown fibrils, whereas solution-grown fibrils were 7-40 nm thick. Unlike epitaxially-grown fibrils, fibrils
assembled in solution displayed a presumably helical structure. While fibril assembly in solution occurred on a
time scale of hours to days, on mica surface fibrils appeared within a few minutes. The nanomechanical behavior
of Aß25-35 fibrils was characterized by the appearance of force staircases which correspond to the force-driven
unzipping and dissociation of protofilaments. Both types of fibrils showed similar plateau-like nanomechanical
responses, however the plateau-force distribution was unimodal for epitaxially-grown fibrils and bimodal for
solution-grown fibrils. The IR spectra contained an intense peak indicative of beta-sheet structure: 1630 cm-1 and
1623 cm-1 for epitaxially grown fibrils and for fibrils assembled in solution respectively. The shift in the amide I
band towards smaller wave numbers indicates a more compact structure. Thus, while both fibrils types display
an underlying beta-sheet structure, they are slightly different: solution-grown fibrils are more compact with a
pronounced axial periodicity.
151
P/I-6
TEMPERATURE-PRESSURE STABILITY AND T-P PHASE DIAGRAM
OF PARVALBUMIN
Judit Somkuti1, Merima Bublin2, Heimo Breiteneder2, László Smeller1
1
2
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Austria
Fish allergy is associated with IgE-mediated hypersensitivity reactions to parvalbumins, which are small calciumbinding muscle proteins and represent the major and sole allergens for 95% of fish-allergic patients.
We performed high pressure Fourier transform infrared spectroscopy experiments to explore the T-p phase
diagram of cod parvalbumin (Gad m 1) and to elucidate possible new ways of pressure-temperature inactivation
of this food allergen.
We followed the secondary structure of the protein as well as the Ca2+-binding to aspartic and glutamic acid
residues. The phase diagram was found to be quite complex containing partially unfolded and molten globule
states. A strong correlation was found between Ca2+-binding and the conformation of the molecule. The
pressure-caused partially unfolded state was reversibly refolded. The completely unfolded molecule, however,
where Ca2+ was released could not refold. The heat-unfolded protein was trapped either in the aggregated state or
in the molten globule state with an absence of aggregation at elevated pressure.
Supervisor: László Smeller
152
2012. április 12-13.
P/I-7
RENAL FUNCTION IS ASSOCIATED WITH RED CELL DISTRIBUTION
WIDTH INDEPENDENT OF IRON DEFICIENCY AND NUTRITIONAL
STATUS IN KIDNEY TRANSPLANT RECIPIENTS
Ákos Ujszászi1, Mária Eszter Czíra1, Ádám Remport2, Csaba Pál Kövesdy3, Anna Rudas1,
Miklós Zsolt Molnár4, István Mucsi4
1
2
3
4
Institute of Behavioral Sciences, Semmelweis University, Budapest
Dept. of Nephrology, Szent Imre Hospital, Budapest
Salem VA Medical Center, Salem, Virginia, USA
Background: Red cell distribution width (RDW), a measure of heterogeneity in the size of circulating
erythrocytes, reportedly predicts mortality in patients with various cardiovascular diseases. RDW is thought to
reflect iron deficiency, inflammation and nutritional status. Impaired renal function is a predictor of mortality in
various patient populations, including patients with chronic kidney disease and it is also associated with
inflammation and protein-energy wasting. Here we wanted to assess if renal function is associated with RDW
independent of iron deficiency, inflammation and nutritional status in stable kidney transplant (KT) recipients.
Methods: We examined association of RDW with eGFR in a cohort of 807 prevalent KT recipients not
receiving erythropoietin stimulating agents. Associations were examined in regression models adjusted for age,
sex, comorbidity (Charlson Comorbidity Index), blood hemoglobin, iron indices (percentage of hypochromic
reticulocytes, soluble transferrin receptor, serum ferritin and transferrin), markers of nutritional status and
inflammation (serum CRP and albumin), markers of bone and mineral metabolism (serum PO4 and iPTH) and
the use of immune suppressants.
Results: Lower eGFR was associated with significantly higher RDW (r=-0.399, -<0.001). This association
remained highly significant even after multivariable adjustments (beta=-0.178, p<0.001). The results were
consistent in subgroups of patients with different levels of kidney function and various markers of inflammation
and iron status.
Conclusions: Lower eGFR is associated with higher RDW, a predictor of mortality, independent of
comorbidity, iron deficiency, inflammation and nutritional status in kidney transplant recipients. Further studies
to determine the potential mechanisms linking impaired renal function to increased RDW may yield new
knowledge about the mechanisms linking CKD to increased mortality.
circulation
Supervisor: Miklós Zsolt Molnár
153
154
2012. április 12-13.
P/II
Chairman:
Dr. Csaba Fekete
155
156
2012. április 12-13.
P/II-1
NMDA RECEPTORS IN GABAERGIC SYNAPSES DURING
POSTNATAL DEVELOPMENT
Csaba Cserép1, Eszter Szabadits1, András Szőnyi1, Masahiko Watanabe2, Tamás F. Freund1,
Gábor Nyiri1
1
2
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest
Hokkaido Uniersity,Scool of Medicine, Sapporo, Japan
GABA exerts depolarizing actions during development and this GABAergic depolarization cooperates with
NMDA-receptors (NMDARs) to drive spontaneous synchronous activity (SSA) that is fundamental for neuronal
development. Surprisingly however, the exact subcellular localization of NMDARs relative to GABAergic
synapses is unknown. Here, we investigated the subcellular distribution of NMDARs at the developmental stage
when GABA depolarizes neurons and SSA is most prominent in mice. Using confocal laser-scanning microscopy
in developing mouse hippocampus, we found that NMDARs were associated with both glutamatergic and
GABAergic synapses at postnatal day 6-7 and we observed a direct colocalization of GABAA- and NMDAreceptor labeling. Electron microscopy of pre-embedding reactions confirmed that GluN1, GluN2A and
GluN2B NMDAR subunits were all expressed in both glutamatergic and GABAergic synapses, and they were
exclusively postsynaptic. Finally, quantitative post-embedding immunogold labeling revealed that the density of
NMDARs was 3 times higher in glutamatergic than in GABAergic synapses. Since GABAergic synapses were
larger, there was very little difference in the total number of NMDA receptors in the two types of synapses. In
addition, receptor density in synapses was almost two orders of magnitude higher than extrasynaptically. These
data suggest that synaptic GABAAR currents trigger NMDAR activation first right inside GABAergic synapses
and this effective spatial cooperation of receptors contributes to the spread of depolarization that reaches
developing glutamatergic synapses.
Supervisor: Gábor Nyíri
157
P/II-2
POSTERIOR THALAMIC TIP39 NEURONS PROJECT TO THE MEDIAL
HYPOTHALAMUS AND REGULATE PROLACTIN SECRETION IN
MOTHERS
Melinda Cservenák1, Ibolya Bodnár2, György M. Nagy2, Ted B. Usdin3, Miklós Palkovits1,
Árpád Dobolyi1
1
2
3
Neuromorphological and Neuroendocrine Research Laboratory, Departments of Anatomy,
Histology, and Embryology, Budapest
Human Morphology and Developmental Biology, Hungarian Academy of Sciences and
Section on Fundamental Neuroscience, National Institute of Mental Health, Bethesda, Maryland
Tuberoinfundibular peptide 39 (TIP39)-containing neurons are activated during lactation in the posterior
intralaminar complex of the thalamus (PIL) in mother rats and, during this period they express TIP39 peptide
and mRNA at higher levels than control females and pup-deprived dams.
We describe the topographical distribution of TIP39 neurons in relation to calcium-binding proteins and report
that calbindin but not calretinin or parvalbumin coexpress with TIP39 in the PIL. Injection of the anterograde
tracer biotinylated dextran amine into the PIL resulted in labeled axon terminals in medial hypothalamic nuclei
including the arcuate, peri-, paraventricular and dorsomedial hypothalamic nuclei, where the receptor of TIP39,
the parathyroid-hormone 2 receptor (PTH2R) is also present in relatively high concentrations. Furthermore, a
high number of retrogradely labeled TIP39 neurons in the PIL were seen after injection of the retrograde tracer
cholera toxin beta subunit in the medial hypothalamic nuclei confirming that these neurons project to the medial
hypothalamus. Subsequently, the function of TIP39-containing neuronal projections was addressed. A genetically
modified lentivirus expressing GFP for visualization of infected cells and the PTH2R antagonist HYWH-TIP39
(as well as a control GFP-tagged virus) was injected into the medial hypothalamus of female rats, 2 weeks before
mating. Blood samples were taken via jugular catheters on 12 days postpartum for the measurement of serum
prolactin levels. Dams injected with HYWH-GFP lentivirus showed significantly reduced basic prolactin levels.
Furthermore, suckling resulted in lower prolactin levels in them after returning the pups following a 4h
separation period.
These results strongly suggest that TIP39 neurons in the PIL project to the medial hypothalamus and regulate
prolactin release in rat dams.
Support: Bolyai Fellowship, OTKA NNF85612 and K100319 grants for AD, OTKA-81522 grant for GMN, OTKA
CK80180 grant for MP, and the NIMH Intramural Research Program for TBU.
Program: Neurosciences and cell biology
Supervisor: Árpád Dobolyi
158
2012. április 12-13.
P/II-3
OPTOGENETIC APPROACH FOR INVESTIGATION OF NEURONAL
MATURATION
Tímea Kőhidi
Institute of Experimental Medicine of Hungarian Academy of Sciences, Budapest
Spontaneous electrical activity of developing neural circuits has an important role during brain development not
only in synaptogenesis and neural network formation, but also in generating mature phenotypes of neurons.
Investigation of these questions on the cellular level however, would be facilitated by appropriate in vitro model
systems.
Recently, we have developed a xeno-free in vitro model system for studying neural stem cells and neural cell
development. Unique, rapid procedure for isolating radial glia-like (RGl) neural stem cells (from both embryonic
and adult rodent brain) is provided by their preferential adhesion to surfaces covered with a novel synthetic
adhesive polypeptide (AK-cyclo[RGDfC]. Radial glia-like neural stem/progenitor cells could be differentiated
into neurons, astrocytes and oligodendrocytes under appropriate inducing conditions.
However, the in vitro maturation of RGl-derived neurons was halted presumably because of the absence of
appropriate electrical stimuli. In order to verify this presumption and to generate mature neurons in vitro, we
intended to develop an optogenetics-based approach. We transfected RGl clones with channelrhodopsin2
transgene, coding a light-activated cation-channel. We hope that by the controlled illumination of RGl-derived
neurons expressing ChR2, we can mimic electrical activity necessary for neuronal maturation.
Doctoral School: "János Szentágothai" Neurosciences
Supervisor: Emília Madarász, Károly Markó
159
P/II-4
ALTERED DEVELOPMENT OF HYPOTHALAMUS IN INTRAUTERINE
UNDER NOURISHED RATS MAY CONTRIBUTE TO METABOLIC
DISORDERS IN ADULTHOOD
Neuromorphological and Neuroendocrine Research Laboratory, Department of Anatomy, Histology
and Embryology, Semmelweis University and the Hungarian Academy of Sciences, Budapest
Intrauterine under nutrition is a high risk factor for developing diabetes, obesity and cardiovascular diseases in
adulthood. To investigate the role of the central nervous system in this process, maternal food restriction was
performed from gestational day 0 (day of mating) to postnatal day 5 by keeping the dams on protein reduced diet
(PR). Cell proliferation marker, BrDU was given intraperitoneally to the dams on gestational days 11, 13 or 15.
After weaning, male pups were selected and kept either on control, or on high fat diet. At the age of 75 days rats
were sacrificed, and the hypothalami processed either for quantitative in situ hybridization, or for BrDU
immunohistochemistry. PR rats had lower birth weight and showed a delayed embryonic cell proliferation in the
hypothalamus. After weaning, PR pups grew faster than the controls. Additionally, MCH, Nesfatin-1/NUCB2
and PrRP mRNA expressions all were elevated in food intake regulatory centers in the hypothalamus in PR
adults. High fat diet consumed after weaning reduced MCH and increased PrRP mRNA expressions, but had no
effect on nesfatin-1/NUCB2 mRNA expression indicating a proper regulatory mechanism by leptin. However,
icv administration of nesfatin-1 resulted in an inadequate response in food intake compared to controls,
suggesting an impaired sensitivity to nesfatin-1. The results suggest that intrauterine under nutrition alters the
development and function of the hypothalamic nuclei related to food intake regulation leading to the
manifestation of metabolic disorders in adulthood.
Supported by CK-801/80 (M.P.) ETT 495/05. (ZE. T.).
Doctoral School: "János Szentágothai "Neurosciences
Supervisor: Zsuzsanna Tóth
160
2012. április 12-13.
P/II-5
PHARMACOGENOMICAL SIGNIFICANCE OF MITOCHONDRIAL DNA
SUBSTITUTIONS
Clinical and Research Centre for Molecular Neurology, Semmelweis University, Budapest
Background : The cornerstone of personalized medicine is pharmacogenomics, which allows to the side effects
of drugs using genetic tests to predict. In somatic genes coding for enzymes involved in metabolism of drugs,
side effects can predicted gene by testing polymorphisms (SNP), but also some of the mitochondrial DNA
polymorphisms have also pharmacogenomical significance. The linelzolid induced lactic acidosis and
aminoglycoside induced deafness have been associated with several specific mtDNA nucleotide polymorphism
and based on the literature, we also know that children have suffering from mtDNA depletion valproate
treatment induces severe hepatotoxicity with eventually a fatal outcome. Metformin, a medicine widely used to
treat type II diabetes mellitus may induce severe lactic acidosis. The exact mechanisms and genetic background
are not known yet.
Methods : To investigate the occurrence of two single nucleotide polymorphisms (SNP) described in the
background of aminoglycoside induced deafness (mt.G1555A, mt.C1494T) we have tested 30 people suffering
from aminoglycoside induced deafness , 160 patients with mitochondrial disease and 150 control subjects using
a PCR-RFLP genotyping technique. The entire sequence of the mitochondrial DNA was also determined with
resequencing (MitoChip v.2.0), and the relevant SNPs validated by Sanger sequencing (ABI Prism 3500) in 18
samples of patients whose family history and histological data obtained form muscle biopsy samples suggested
mitochondrial disease.
Results : The mtDNA SNP G1555A predisposing for aminoglycoside induced deafness was found in 12 cases in
heteroplasmic form of the 340 investigated individuals (5 patients with mitochondrial disease and in 7 controls
patients). We could not detect the C1494T SNP in any of the cases. In patients examined with MitoChip v.2.0
three SNPs’ with pharmacogenomic significe were found, all of them are also haplotype markers. We report a
case of a 55-year-old man with diabetes mellitus who received metformin treatment,in addition to extremely high
serum lactate level (5.7 mmol / l) severe myalgia, and insulin resistance could be observed. After leaving the
metformin the lactate level decreased by 2.5 mmol / l and insulin requirement returned to normal. We have
found with the resequensing of the complete mtDNA ten susceptability SNPs for complex disorders, and four
SNPs connected with the Maternally inherited diabetes and deafness (MIDD). The A2706G SNP is associated
with linezolid induced lactic acidosis, this SNP was detected in both of the patients suffering from side effects of
metformin.
Discussion : SNPs of mitochondrial genome can also provide important pharmacogenomic information,
allowing side effects prevention of some drug. Further investigations of predisposing genomic factors for
metformin induced lactic acidosis are still ongoing in our laboratory.
Doctoral School: "János Szentágothai" Neurosciences
Program: Clinical neuroscience
Supervisor: Mária Judit Molnár
161
162
2012. április 12-13.
P/III
Chairman:
Prof. Dr. Péter Lakatos
163
164
2012. április 12-13.
P/III-1
CAN HUMAN DNA ACTIVATE IMMUNE CELLS VIA TLR9?
CYTOKINE PROFILE OF HT-29 CELLS TREATED WITH HUMAN DNA
ISOLATED FROM HUMAN CANCER CELLS
István Fűri1, Sándor Spisák2, Árpád V. Patai1, Ferenc Sipos1, Barnabás Wichmann1, Orsolya
Galamb1,2, Gábor Valcz1, Alexandra Kalmár1, Bálint Péterfia3, Katalin Leiszter1, Kinga Tóth1,
Andrea Schöller1, Barbara Kinga Barták1, Zsófia Brigitta Nagy1, Tibor Krenács3, Béla Molnár1,2,
Zsolt Tulassay1,2
1
2
3
Budapest
Background: Toll-like receptors recognize specific motifs which are frequently expressed in bacteria, fungi,
prokaryotes and viruses. Toll-like receptor 9 (TLR9) can be activated by (unmethylated) cytosin-guanine
dinucleotide containing bacterial or viral DNA, imunoglobulin-DNA complexes and synthetic
oligodeoxynucleotide (ODN) sequences.
Aims: Our primary aim was to prove that human DNA isolated from a human cancer cell line can activate
immune cells via TLR9. Our further aim was to examine changes in the signal transduction pathway downstream
of activated TLR9 and to analyze the expression of DNA methyltransferase enzymes before and after DNA
treatment.
Methods: Genomic DNA was isolated from 5x107 HT-29 cells. Subsequently, 2x106 HT-29 cells were treated
with 4.45µg of DNA per well in 2 ml RPMI 1640 without BSA. After 6 hours the cells were harvested and total
RNA was isolated both before and after DNA treatment using Qiagen RNeasy Mini Kit. Expression levels of 52
genes including (TLR, IL, other cytokines, apoptotic receptors) were examined by RT-PCR. From the treated and
untreated sample immunocytochemistry was performed for TLR9, DNA methyltransferases (DNMT1,
DNMT3a, DNMT3b) proliferation and differentiation factors (CDX2, CK).
Results: Analysis of 52 genes in PCR showed altered mRNA expression at key adaptor molecules in TLR9
pathway. Immunocytochemistry in treated sample showed overexpression of CK and DNMT3a.
Conclusion: Due to our results the increased extracellular DNA concentration can influence the tumorous
process through the TLR pathway by releasing the members of IL family/ proinflammatory cytokines.
165
P/III-2
VENULAR DIAMETER REGULATORY ROLE OF THE VASCULAR
ENDOTHELIAL GROWTH FACTOR (VEGF) IN DIFFERENT
CONDITIONS OF RAT GINGIVA
Milán Gyurkovics1, Zsolt Lohinai1, Adrienne Győrfi1, Csaba Bodor2, Andrea Dorottya Székely3, Elek
Dinya4, László Rosivall2
1
Faculty of Dentistry, Department of Conservative Dentistry, Semmelweis University Budapest
Faculty of Medicine, Institute of Pathophysiology, Hungarian Academy of Sciences and
Semmelweis University Research Group for Pediatrics and Nephrology, Semmelweis University
Budapest
3
Faculty of Medicine, Department of Anatomy, Histology and Embryology, Semmelweis University,
Budapest
4
Faculty of Medicine, Institute of Health Informatics, Semmelweis University, Budapest
2
Aims: Aim of our study was to investigate the possible regulatory role of VEGF on the gingival venules in rats
under physiological (healthy gingiva) and pathological (gingivitis, diabetes) conditions.
Material and Methods: The investigated materials (VEGF, VEGF receptor type 2 (VEGFR2) antagonist or
saline) were dripped onto the gingiva between the lower incisors. Diameter changes of selected gingival venule
were observed by vital microscopy combined with digital photography at lower incisors in specified times.
Animals with healthy gingiva served as control. Venule diameter changes were compared to the start-up and to
the values of the control group as well. Immunohistochemistry and western blot were also utilized to localize and
to analyze VEGFR2s.
Results: In healthy gingiva, VEGF significantly and dose-dependently increased the venule diameter compared
to saline. VEGFR2 antagonist on its own did not cause any alteration. Premedication with the antagonist
decreased the dilatory effect of VEGF significantly. However, in case of gingivitis and diabetes significant
vasoconstriction occured for the antagonist and VEGFR2 overexpression was also detected both with
immunohistochemical and western blot analysis.
Conclusion: These findings suggest that despite there is no remarkable VEGF production under healthy
condition in gingiva, but VEGF is able to increase the gingival blood flow through the activation of VEGF
receptors. Furthermore, both VEGF production and VEGFR2 expression are increased in gingiva during
gingivitis and diabetes, and VEGF has an important role in the vasodilation of gingival venules. The release of
inflammatory and vasodilatory mediators from mast cells after their VEGFR2 activation may also contribute to
the attendant microcirculatory changes in diabetes.
Program: Dental research
Supervisor: Gábor Varga
166
2012. április 12-13.
P/III-3
GENE EXPESSION-BASED ANALYSIS OF COLORECTAL
DYSPLASIA-CARCINOMA TRANSITION
Alexandra Kalmár1, Orsolya Galamb1, Sándor Spisák1, Barnabás Wichmann1, Ferenc Sipos1,
Tibor Krenács1, Kinga Tóth1, Katalin Leiszter1, Andrea Schöller1, István Fűri1, Zsófia Brigitta Nagy1,
Barbara Kinga Barták1, Zsolt Tulassay2, Béla Molnár1,2
1
2
Background and aims: Though histopathology is still the gold standard for differentiating stages of colorectal
disease progression, the cut slide may represent only a fragment of the whole sample and disease features, such as
dysplastic areas of flat adenomas, may remain hidden due to inappropriate sampling or tissue orientation. The
early molecular detection of the colorectal dysplasia-carcinoma transition may enhance the strenght of diagnosis
from colonic biopsies. Using high-throughput microarray-based biomarker screening low cost diagnostic array
real-time PCR panels may be developed. We aimed to determine molecular markers for enhancing the
differentiation of high-grade dysplasia from colorectal carcinoma (CRC) and to analyze the applicability of FFPE
tissue samples.
Material and Methods: Discriminatory transcript set was identified using HGU133plus2.0 microarrays
(Affymetrix Inc.) on 53 biopsy samples (22 CRC, 20 adenoma, 11 normal). For testing the classificatory power of
the discriminatory genes, 94 independent biopsies (27 CRC, 29 adenoma, 38 normal) were analyzed on
microarrays. Array real-time PCR validation was done on 68 independent samples (24 CRC, 24 adenoma, 20
normal) using LightCycler®480 system (Roche) and RealTime ready assays. Reverse transcription was done using
Transcriptor First Strand cDNA Synthesis Kit (Roche). For testing the applicability of FFPE tissues, total RNA
was isolated from 10um-thick slides of 5 CRC and 2 adjacent normal samples using High Pure RNA Paraffin Kit
(Roche). The same cDNA synthesis and real-time PCR conditions were applied as in case of fresh frozen
samples.
Results: A set of 11 transcripts (including CXCL1, MMP3, GREM1) was determined which could correctly
discriminate between not only the normal, adenoma and CRC samples, but between high-grade dysplastic
adenoma and CRC samples by 100% sensitivity and 88.9% specificity. The discriminatory power of the marker
set was proved to be high on independent fresh frozen biopsy samples in both microarray and RT-PCR analyses.
95.6% of original and 94.1% of cross-validated samples were correctly classified in discriminant analysis.
According to the RT-PCR results for the set of 11 markers, tumorous and normal FFPE tissue samples could be
distinguished by 100% sensitivity and specificity.
Conclusion: The identified transcripts could correctly characterize the dysplasia-carcinoma transition in colonic
tissue samples, also on a large independent sample set and on FFPE tissue samples. These markers can establish
the basis of gene expression based diagnostic classification of colorectal cancer. Diagnostic panels can become
part of the automated routine procedure.
167
P/III-4
RENIN-ANGIONTENSIN-ALDOSTERONE-SYSTEM BLOCKERS IN
DIABETIC NEPHROPATHY: THE ROLE OF THE SIGMA-1 RECEPTOR
Lilla Lénárt1, Nóra Fanni Bánki 1,2, Ágota Vér 3, László Wagner 4, Ágnes Prókai 1,
Sándor Kőszegi1,2, Ádám Hosszú 1,2, Attila Szabó 1, Andrea Fekete 1,2
1
2
3
Department of Medical Chemistry, Moecular Biology and Pathobiochemistry, Semmelweis
4
Department of Transplantation Surgery, Semmelweis University, Budapest
5
Introduction: Renal renin-angiotensin-aldosterone system (RAAS) is clearly activated in diabetes, which is the
main cause of end-stage renal failure. ACE inhibitors and angiotensin II receptor blockers (ARBs) are the routine
therapy to slow the progression of diabetic nephropathy (DN); however aldosterone antagonists are only used as
adjuncts. Here we compare the renoprotective effect of various angiotensin and aldosterone blockers used in
monotherapy to test their influence on the Sigma-1 receptor (1R)–Akt–endothelial nitrogen monoxide synthase
(eNOS) pathway in the development of DN.
Methods: Streptozotocin-diabetic rats were treated p.o. with enalapril, losartan, spironolactone or eplerenone for 2
weeks. Vehicle-treated diabetic and non-diabetic animals were controls (n=8-10/group). Metabolic and kidney
function, renal morphology, protein levels of Sigma-1R, Akt, phosphor-Akt (pAkt) and eNOS levels were
analyzed.
Results: Structural damage of diabetic kidneys were ameliorated by each RAAS inhibitor, while kidney function
was mostly preserved by aldosterone antagonists. Diabetes-induced decrease of Sigma-1R, phospho-Akt and
eNOS level was restored by RAAS inhibition.
Discussion: The Sigma-1R – Akt – NKA pathway might play a role in the pathophysiology of DN and could
serve as a novel additional target of RAAS blockers. A monotherapy with aldosterone antagonists might be as, or
more effective than ACEi or ARBs in the prevention of STZ-induced DN.
Lilla Lénárt is a graduate student
168
2012. április 12-13.
P/III-5
INVESTIGATION OF THYMIDYLATE SYNTHASE GENE
POLYMORPHISM IN COLON CANCER PATIENTS
Andrea Schöller1,2, Alexandra Kalmár1, Árpád V.Patai1, Zsófia Nagy1, Barbara Barták1,
Orsolya Galamb1, Sándor Spisák1, Lídia Sréter1, Béla Molnár1,3, Zsolt Tulassay1,3
1
2
3
2nd Deptament of Internal Medicine, Semmelweis University, Budapest
2nd Deptament of Surgery, Semmelweis University, Budapest
Background: Thymidylate synthase enzyme is essential for DNA repair and biosynthesis and it is involved in
cell proliferation as well. A 28bp variable tandem repeat (VNTR) a G/C single nucleotid polimorphism at the
5’UTR and a deletion of 6bp at the 3’UTR were described. Thymidylate synthase is the therapeutic target of 5fluorouracil based chemotherapy and its alterations could change the therapeutic response.
Aims: Our aims were to compaire the thymidylate synthase polimorphism between healthy tissue and colon
cancer and examinate the efficacy of 5-FU according to genetic variants.
Materials and methods: The retrospective study was carried out on paraffin-embedded sections from 14 Dukes
C and D colon cancer patient. Fifteen 10µm section were deparaffinated used paraffin dissolver (MachereyNagel) from each patients healthy and cancer blocks. After overnight Proteinase K digestion DNA were isolated
by High Pure PCR Template Preparation Kit (Roche). After PCR (LightCycler 480 Probes Master Mix, Roche)
amplification the ins/del analysis were performed by DraI digestion followed by capillary gelelectrophoresis and
the number of VNTR fragments were detected by capillary gelelectrophoresis (DNA1000 Kit, Bioanalyzer 2100,
Agilent). The SNP were evaluated by sequention analysis ( ABI PRISM 310 Genetic Analyser ).
Results: No significant differencies were detected between 2R/3R and 3R/3R group and slightly better survival
linked to 2R/2R genotype. Patient with homozygous C allele shows longer survival. The 1494 deletion
associated to reduced chemotherapy response. Differencies between healthy and cancer tissue have not been
found.
Conclusion: Our results suggest that the polymorphism of TS gene may provide a more effective prediction of
the clinical outcome of 5-FU therapy.
169
P/III-6
COGNITIVE FUNCTION IN PATIENTS WITH TYPE 1 DIABETES
Barbara Szémán1, Géza Nagy1, Anna Veres-Székely2, Mária Sasvári3, Dávid Fitala1, Adrienn
Szöllősi1, Orsolya Hadarits4, Zahra Al-Aissa1, Anikó Somogyi1
1
2
3
4
Faculty of Education and Psychology, Institute of Psychology, Eötvös Lóránd University,
Budapest
First Department of Obstetrics and Gynecology, Semmelweis University, Budapest
Most of the data suggest that the patient with diabetes have reduced performance on numerous domain of
cognitive function. In patients with type 1 diabetes (T1DM), specific and global deficits evolving speed of
psychomotor efficiency, information processing, mental flexibility, attention, and visual perception seem to be
present. Complex pathophysiology of changes in central nervous system in T1DM has not yet been fully
elucidated.
Aims : Our aims were to compare executive function in patient with T1DM to healthy controls (C), and evaluate
the association between executive dysfunction and the diabetes specific parameters.
Methods : One domain of the cognitive function, the executive function was studied in 64 patients with T1DM
(age: 35,63±11,45, 35 men and 29 women), and 64 control participants (age: 32,63±11,45, 35 men and 29
women), who were matched for sex and age. Two computerized neuropsychological test was used as a tool in the
evaluation of executive functions. The Stroop test is considered to measure selective attention and the Wisconsin
Card Sorting Test (WCST) to examine the integrity of frontal lobe functions.
Results : In Stroop-test significantly larger (p=0,005) Stroop-test interference score (106,97±73,16 msec) were
found in patients with type 1 diabetes than individuals without diabetes (72,27±64,44 msec). The performance
showed association with HbA1C and the duration of diabetes (p=0,026).
The performance measured with WCST was worse in diabetic patients (ratio of correct answer: 78±8,56%, ratio
of perseverative errors: 39,5±11,7%) compared with individuals without diabetes (ratio of correct answer:
80,39±8,23%, ratio of perseverative errors: 36,92±9,43%), however this differences weren’t statistically
significant (p>0,05).
Conclusions : Our results suggest that the patients with diabetes have reduced executive function compared with
individuals without diabetes. The poor carbohydrate metabolism may induce attention dysfunction in patients
with T1DM. Stroop test performance and the responsible regions of the brain may be more sensitive to chronic
hyperglycaemia than other areas.
Supervisor: Anikó Somogyi
170
2012. április 12-13.
P/III-7
DETECTION OF METHYLATED SEPT9 PERIPHERAL BLOOD
SCREENING MARKER IN BOTH LEFT - AND RIGHT - SIDED COLON
CANCER AND COMPARISON TO FOBT AND CEA
Kinga Tóth1, Jürgen Beck3, Kerstin Buser3, Zsófia Brigitta Nagy1, Barbara Kinga Barták1, Robert
Stöhr4, Henriette Golcher5, Vera Schellerer5, Zsolt Tulassay1,2, Béla Molnár1,2
1
2
3
4
5
Epigenomics AG, Berlin, Germany
Institute for Pathology, University of Erlangen, Germany
Department of Surgery, University of Erlangen, Germany
Background: Methylated SEPT9 (mSEPT9) DNA is a sensitive and specific biomarker for the detection of
colorectal cancer (CRC) from peripheral blood. Many aspects of the biology of mSEPT9 in the plasma of CRC
patients have yet to be explored, including relationship to CRC location, FOBT positivity and other blood-based
tumor markers.
Aims: 1) Determine the sensitivity of mSEPT9 for CRC detection in the left- and right-sided CRC2) Compare
m
SEPT9 and FOBT positivity rates in individuals with no evidence of disease (NED) and CRC patients. 3)
Compare mSEPT9 and another blood-based tumor marker, carcinoembryonic antigen (CEA), in NED and CRC
patients.
Materials and Methods: Plasma samples for mSEPT9 analysis were collected from NED (n = 92) and CRC
(n = 92) after colonoscopy. Total DNA was prepared and bisulfite-converted using the Epi proColon kit 2.0
(Epigenomics AG, Germany). Qualitative determination of total DNA and mSEPT9 was performed using the Epi
proColon 2.0 real time-PCR assay (Roche LC480). Samples for FOBT were collected from NED (n = 17) and
CRC (n = 22) prior to colonoscopy. Serum samples for CEA analysis were collected from NED (n = 27) and
CRC (n = 27).
Results: mSEPT9 values were detected in 15.2 % (14/92) NED and 95.6 % (88/92) CRC. FOBT was positive
for 29.4 % (5/17) NED and 68.2 % (15/22) CRC. Positive CEA results were detected in 14.8 % (4/27) of NED
and 51.8 % (14/27) CRC. When analyzed according to location within the colon, mSEPT9 was positive in 96.4 %
(54/56) of left-sided CRC and 94.4 % (34/36) of right-sided CRC. FOBT was positive in 66.7 % (10/15) of leftsided CRC and 33.3 % (5/15) of right-sided CRC. CEA was positive in 64.3 % (9/14), of left-sided CRC and
35.7 % (5/14) of right-sided CRC.
Conclusion: mSEPT9 was confirmed as a highly sensitive biomarker for the detection of CRC in blood. SEPT9
methylation level has no difference between left and right side colon cancer. mSEPT9 showed higher sensitivity
for CRC compared to FOBT in CRC, specially in right sided cancers. Plasma mSEPT9 showed higher sensitivity
in both sides of CRC then blood CEA.
171
172
2012. április 12-13.
P/IV
Chairman:
Dr. Attila Patócs
173
174
2012. április 12-13.
P/IV-1
THE COMPACT MUTATION OF MYOSTATIN CAUSES SKELETAL
MUSCLE HYPERPLASIA
Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged
Introduction: Myostatin, a member of the TGF-β superfamily, is an important negative regulator of skeletal
muscle growth. Silencing myostatin gene in knockout mice causes a hypermuscular phenotype characterized by
both muscle hyperplasia and hypertrophy. Compact (Cmpt) mice, which carry a 12-bp-deletion in the propeptide
region of myostatin, shows a hypermuscular character as well. Since very little is known about the mechanism of
muscle overgrowth in these mice we aimed at analyzing the Cmpt phenotype. First, we determined whether the
muscles of Cmpt mice show either hyperplasia or hypertrophy or both.
Methods : Ten-week old male Cmpt vs. control CFLP mice were used for the experiments (n=3-4). Typical
hindlimb muscles (m. quadriceps, m. tibialis anterior, m. extensor digitorum longus, m. soleus, m. gastrocnemius)
of both strains were removed under ip. anaesthesia, the muscles were weighed and frozen in isopenthane/ liquid
nitrogen. 10 µm-thick cryostat sections were made from the midbelly region of m. tibialis anterior followed by
standard hematoxylin-eosin staining. Pictures from all microscopic fields of each muscle were reconstructed
using the Cell B programme and the number and size of muscle fibers were analyzed by Digimizer software on
the whole cross-sectional area.
Results : All muscles of the Cmpt mice were significantly larger compared to those of control ones. The number
of muscle fibers in m. tibialis anterior of the Cmpt mice increased significantly (5242±455 vs. 3381±187 (Cmpt vs.
CFLP, mean±SD)). The peak of the curve representing fiber size distribution in Cmpt mice were shifted towards
larger fibers, however, because of the narrower character of the curve no significant difference were detected in
the mean fiber size between the two strains (2114±205 vs. 2527±212 µm2). Thus, in contrast to myostatin
knockout, hypermuscularity of Cmpt mice was caused exclusively by fiber hyperplasia which suggests a different
mechanism of muscle overgrowth in these mice.
Program: Biochemistry, biophysics, molecular- and cell biology
Supervisor: Luca Mendler
175
P/IV-2
A NOVEL BURSAL STEM CELL ANTIGEN: CHARACTERIZATION
AND ONTOGENIC STUDY
Nóra Fejszák
The avian embryo provides an excellent model to study the development of the lympho-myeloid system. As an
effort to learn how lympho-myeloid diversification is regulated in the avian embryo we have produced
monoclonal antibodies (mAbs) by immunizing mice with cell suspension of spleen and bursa of Fabricius.
One of these mAb (7H3) was found to recognize a cell surface antigen expressed by hematopoietic cells as they
emerge in the embryo but disappears around hatching except on T cells and subpopulation of cortical B cells of
bursal follicles. In order to confirm the hematopoietic specificity of 7H3 co-stainings with common leukocyte
antigen CD45 were carried out. After hatching the 7H3 antigen was restricted to the lymphoid cells, as other cells
of lympho-myeloid origin, macrophages, dendritic cells, granulocytes did not react with 7H3 mAb. The 7H3
mAb does not crossreact with other avian species and can be useful in chimeric experiments to study the
developmental capacities of 7H3 positive B cells present in the adult bursal follicles. By grafting adult guinea fowl
bursal follicles to chicken embryo it was possible to demonstrate that the 7H3 positive B lymphocytes of the
adult bursa of Fabricius can colonize the host embryonic bursal follicles. This chimeric result indicates that 7H3
mAb may be a reliable proof of the presence of stem cells in adult lymphoid organs.
In conclusion: The first 7H3 positivity appear on hematopoietic cells of the yolk sac blood islands. In adult
guinea fowl the 7H3 antibody recognizes all T cells and a subpopulation of B cells in the bursal follicles. Based
on these result, we assume that the 7H3 mAb labels a new differentiation antigen and can be useful marker to
characterize the early hematopoietic cells in the embryo and postbursal stem cells of the bursa of Fabricius.
Supervisor: Nándor Nagy
176
2012. április 12-13.
P/IV-3
EFFECT OF THE COMPACT MUTATION ON THE GLYCOGEN
CONTENT OF SKELETAL MUSCLE
Department of Biochemistry, Faculty of General Medicine, University of Szeged
Introduction: The TGF-beta family member myostatin is a potent negative regulator of skeletal muscle mass.
Compact (Cmpt) mice carry a naturally occurring 12-bp deletion in the propeptide region of the myostatin
precursor, and additional modifiers are involved in determining the full expression of the hypermuscular
phenotype. Myostatin knock out and Cmpt mice show skeletal muscle hypertrophy, however, this increase in
muscle mass is not accompanied by a proportionate increase in muscle force. Our aim was to further characterize
the phenotype of Cmpt mice and analyse the glycogen content of the muscles.
Methods: Frozen sections of tibialis anterior muscles of Cmpt and control CFPL mice (n=3-4) were stained by
PAS to visualize glycogen content of the samples. The full cross sectional areas of the muscles were
reconstructed from the microscopic photos by Cell B software, the size of the fibers was measured by Digimizer
programme and the intensity of PAS staining was densitometrically analysed on greyscale images (0-1 OD).
Results: The body weight and the weight of hindlimb muscles of Cmpts significantly increased, and weight of
investigated organs (heart, liver, kidney) significantly decreased compared to CFLPs. In the fibers of tibialis
anterior muscle of the Cmpt mice the average intensity of PAS staining was lower compared to CFLPs
(0,46±0,036 vs. 0,595±0,036 OD, mean±SD). The glycogen content per fiber was significantly lower in Cmpt
animals (976,4±116,6 vs. 1509±149,8 OD*µm2). Frequency distribution of fibers with different glycogen content
showed different pattern in Cmpts versus CFPLs, the curve was narrower and shifted towards fibers with low
glycogen content; however, the glycogen content per full cross sectional area did not change significantly. Based
on our results the glycogen content of Cmpt fibers was reduced which can explain the lack of muscle force
increase observed previously.
Supervisor: László Dux, Anikó Keller-Pintér
177
P/IV-4
EFFICIENCY OF TRANSFECTION ALONG THE REGENERATING
SOLEUS MUSCLE
Department of Biochemistry, Faculty of Medicine, University of Szeged
Muscle fibers almost extend from proximal to distal ends in the soleus of young adult rats. However, after
injection with plasmid DNA, only a small ratio of fibers becomes transfected in the central part of the
regenerating muscle. Our aim was to investigate how transfection efficiency changes along the longitudinal axis
of the regenerating soleus and to check if it is a result of reduced fiber length in regeneration.
Muscle regeneration was induced by notexin and the soleus was transfected by EGFP or DsRed expressing
plasmids. After dissection, muscles were divided into six segments for cross sections and into three segments for
longitudinal sections. Fiber length was investigated by staining neuromuscular junctions (NMJ) for
acetylcholinesterase; one NMJ belongs to one fiber inmammals.
The results showed a decrease in transfection efficiency toward the ends of regenerating muscle. The NMJ-s were
positioned in the central part of the regenerating muscles like in the normal ones.
We conclude that the decline of transfection efficiency from the place of injection toward the muscle ends is
probably not a result of reduced fiber length but it is more likely due to the limited diffusion of the transfected
and expressed molecules.
Supervisor: Ernő Zádor
178
2012. április 12-13.
P/IV-5
MISPLACED PHOTORECEPTORS DURING POSTNATAL
DEVELOPMENT IN THE RAT RETINA
In the retina of the primarily nocturnal animals, rod photoreceptors are the dominant components in signal
perception. Their photosensitive pigment -rhodopsin- can be detected with immunocytochemistry from birth.
Previous studies showed, that besides the extensive staining of the photoreceptors, a less numerous population of
cells was also labeled in the inner nuclear, and ganglion cell layers during postnatal development. The aim of the
present study was to describe the morphology and the staining characteristics of this peculiar population in the
rat retina.
Retinas of Spague-Dawley rats of different ages (P0-P21) were studied. Immuncytochemical labeling of different
rhodopsin specific antibodies were used on whole mounted retinas and cryosections. Double labeling with
several retinal cell type specific antibodies was used to further characterize the rhodopsin positive cell
populations.
We observed rhodopsin expressing cells in the inner nuclear and ganglion cell layers of the rat retina. They
comprised approximately 1% of all labeled cells, often appeared in smaller clusters and morphologically
resembled bipolar, amacrine or ganglion cells. They could be reliably detected using several different sets of
antibodies, raised against the C-, and the N-terminal of rhodopsin, respectively. These cells first appeared at the
4th postnatal day (P4), reached their maximum density at P14 and disappeared entirely by the end of the 3rd
week. Staining with different inner retinal cell type specific antibodies showed colocalization only in case of
recoverin, that is known to label photoreceptors besides bipolar and amacrine cells.
Our results showed that approximately 1% of all rhodopsin expressing cells are not located amongst other
photoreceptors during development, but are displaced to the inner retinal layers. Although they lose almost all
morphological resemblance to photoreceptors, colabeling indicates that they are most probably misplaced rods
that fail to integrate in the retinal mosaic.
Supervisor: Ákos Lukáts
179
P/IV-6
META-ANALYTIC COMPARISON OF PROTEOMIC DATA ON
EXTRACELLULAR VESICLE SUBSETS
Tamás G. Szabó1, Petra Misják1, Borbála Aradi1, Bence György1, Mária Pásztói1,2, Zsuzsanna Pál1,
Krisztina Pálóczi1, Valéria László1, Éva Pállinger1, Erna Pap1, Ágnes Kittel4, K. Taylor-Szabó1,
György Nagy1,3, András Falus1,2, Edit Buzás1
1
Hungarian Academy of Sciences - Semmelweis University, Inflammation Biology and
Immunogenomic Research Group, Budapest
3
Budai Irgalmasrendi Kórház, Budapest
4
Institute of Experimental Medicine of the Hungarian Academy fo Sciences, Semmelweis
2
Background: Distinct populations of extracellular vesicles (EVs) have clearly different size, morphology, and
subcellular origin. Our aim was to study whether distinct types of EVs were also characterized by differential
proteomic composititon.
Materials and methods: Protein contents of EV subsets were analysed on the basis of data accessible in the
ExoCarta Database or extractible from PubMed. Vesicles isolated by density gradient ultracentrifugation were
regarded as exosomes and vesicles sedimented at 15,000 – 20,500g as microvesicles. A third type oft of EV
preparation, isolated with 100,000-200,000g was also studied. Proteomic analysis was done with Ingenuity
Pathway Analysis (IPA) software.
Results: Filtering the literature yielded in 6 exosomal, 5 microvesicular and 6 “high-speed isolation” mass
spectrometry studies, with 738, 1299 and 872 proteins extractable, respectively. A substantial number of nuclear
proteins was also found in EVs, especially in MVs, besides cytoplasmic and membrane proteins. Functional
proteomic analysis by the IPA software suggests that cell movement, cell morphology and cell death are strongly
associated with vesicular proteins.
Conclusions: The overlap between the protein content of different types of EVs suggest the existence of a
common “vesicular proteome”. Differences between EV proteomes, on the other hand, may also be important
to note.
Supervisor: Edit Buzás
180
2012. április 12-13.
P/V
Chaipersons:
Dr. Lajos Simon
Dr. Katalin Hegedűs
Dr. György Purebl
181
182
2012. április 12-13.
P/V-1
POST-ERROR SLOWING IN PATIENTS WITH ATTENTION
DEFICIT/HYPERACTIVITY DISORDER (ADHD) - A META-ANALYSIS
Lívia Balogh1, Szilvia Papp1, László Tombor1, István Bitter1, Pál Czobor1,2
1
2
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY
Background: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder
defined by the behavioral symptoms of inattention, hyperactivity and impulsivity. Recently, in addition to
psychopathological symptoms, investigation of behavioral characteristics, including error monitoring has
become a prominent area of research. After committing an error, healthy control subjects show an increased
latency of response to subsequent stimuli in a reaction time task paradigm, a phenomenon called post-error
slowing (PES). Previous findings from the literature suggest that the extent of PES shows substantial reduction in
patients with ADHD.
Aims: The goal of this investigation was to conduct a meta-analytic summary of PES in ADHD subjects as
compared to healthy controls based on all available (child and adult) studies in the literature. In addition, we also
examined the association between PES and task characteristics and demographic features of the study
population.
Method: Relevant publications were identified using the Medline and PubMed search engines. Searching for
studies published in English between 1988 and 2011, the following keywords were used: ’ADHD’, ’post-error
slowing’, ’post error slowing’, ’reaction time’, ’error’ and ’error monitoring’. Reference lists of identified papers
were also reviewed. The literature search yielded a total of 14 publications, comprising 20 cohorts of ADHD
subjects.
Results: Random effect meta-analysis indicated that the extent of post-error slowing was significantly lower in
patients compared with the healthy control group. Furthermore, the magnitude of PES reduction in ADHD
subjects relative to controls varied significantly with inter-stimulus interval (ISI). Post-error slowing was not
affected by age or gender.
Conclusion: Marked post-error slowing difference between the ADHD and control groups suggests that this
phenomenon may be considered as a behavioral marker, potentially useful for differentiating between ADHD
patients and healthy control subjects.
183
P/V-2
THE ROLE OF CYP POLYMORPHISMS IN THE THERAPEUTIC
EFFECT AND ADVERSE REACTIONS OF PSYCHOTROP DRUGS
Department of Psychiatry and Psychotherapy Semmelweis University, Budapest
Side effects and non-response to treatment with psychiatric drugs may be a result of an altered drug metabolism
caused by the different amount and activity of the liver cytochrome P450 (CYP) enzymes. Genetic and nongenetic variations of CYP enzymes (CYP polymorphisms) are known to influence blood levels of psychiatric
drugs, and thus modify their therapeutic effect and their potential to generate adverse drug reactions. The aim of
the present study is to evaluate the role of the CYP enzymes in the metabolism of the most frequently used
antipsychotics, antidepressants, and mood stabilizers in patients with schizophrenia or bipolar disorder. First we
plan to identify the main CYP enzymes involved in the metabolism of psychiatric drugs, then we qualify the
genotypes and phenotypes of these enzymes in psychiatric patients. Measurement of blood levels of the different
drugs and their metabolites with the clinical evaluation of the therapeutic effect and side effects of the
medications will allow us to confirm the role of the metabolizing status in the response to psychotrop treatment
and it will also help to optimize psychopharmacotherapy. The rationalization and individualization of the therapy
can lead to decreased medical costs, to the reduction of the hospital stay, and to the improvement of the patients’
quality of life.
Supervisor: István Bitter
184
2012. április 12-13.
P/V-3
SUICIDE PREVENTION. THE FAMILY MEMBER'S POSSIBILITIES AND
RESPONSIBILITY
Győző Orbán
Introduction: The suicide is an unsolved worldwide problem. The proportionate number of committed suicide
in Hungary is 2500/year, 6/day. The health screening and the treatment of the depression, which is the primary
cause, is the base of the prevention.
Research objectives: The goal of the research is to analyse the specialities of the 75 committed and 41 intended
suicides in the small region of Dunakeszi–Fót–Göd in 2007-2011 (population 72.831, adults: 61.172) and to make
use of the drawn conclusions within “Suicide Prevention Program”.
Hypothesis: The numbers of suicides have been increased in 2007-2011. In many cases the depression-suicide
intentions of the family members can be detected by the patient's family. The appropriate behaviour of the family
members can be influential in the prevention therefore a moral and legal responsibility can be manifested as well.
Methods, arrangements: Based on the police local reviews/inspection’s reports and notes, the facts were given
by the family members, the farewell letters and other medical documents we have made the list of committed and
intended suicides. We have analysed the active-passive behaviour of the family members before the commitment
and after the suicide attempt. The data were compared using the same cases on the basic of the gender and the
age, we have statistically analysed (committed and intended suicides, the possible vindicative reasons of the
depression).
Results evaluation: 2007-2011: the total numbers of the suicide was 75, 20% more than during the period of
2002-2006(50). The rate of men(58)-women(17): 3,4:1. The number of suicides with earlier attempt: 10, which is
13,3% of the committed suicides. Men-women rate was 2,3:1. From the total suicides the depressed patients were
45,3% (in specialized literature 30%). The suicide intention's: 41, from those the rate of men(11)-women(30): 2,7:1.
Farewell letters: 12. Men-women rate 2:1. Responsibility of the family member's behaviour: 9 intentions were already
repeated from 41. Family help assistance rate: 51,2%. Before commission and intentions 48,8% of the offenders
received medical treatment. The efficiency rate of the health and the families concerning the life-saving of the
committed suicide was 50%.
Conclusions: The number of the suicide in this region had been increased with 20%. The depression is the main
risk factor (45,3%). The inefficiency of the prevention: 50% regarding the total cases. The co-operation with the
family members is improvable in the prevention being involved them to the health screening programs. If the
family member notices the directly danger of suicide, and omits the life-saving request for medical help, the
application of the Penal Code (§172) should be considered.
185
P/V-4
SOCIO-CULTURAL INFLUENCES ON BODY IMAGE
DISSATISFACTION IN ADOLESCENCE
Ildikó Papp1, Edit Czeglédi2, Bernadett Babusa1, Ferenc Túry1
1
2
Semmelweis University, Institute of Behavioral Sciences, Budapest, Hungary
Doctoral School of Psychology, Eötvös Loránd University; Institute of Psychology, Eötvös
Loránd University, Budapest, Hungary
Keywords: adolescence, body image, body dissatisfaction, sociocultural influences, thin body ideal, thin-ideal internalization
This study is an examination of the potential risk factors of body image dissatisfaction (BID), and the mediating
role of thin-ideal internalization. We tested the previously suggested Tripartite Influence Model of appearancerelated sociocultural influences (role of parents, peers, and media) in association with body image dissatisfaction
on 370 adolescents (145 boys and 225 girls, aged 10 to16 years). In the case of girls, weight perception had a
stronger relationship with BID than with BMI. Media and parental influences, and thin-ideal internalization
showed a positive relationship with BID in both genders, while appearance-related peer influence showed an
association only in girls. Lower self-esteem predicted a greater BID in both genders. Thin-ideal internalization
partially mediated the relationship between sociocultural influences and BID in both genders. Prevention and
intervention programs should focus on these risk factors of BID. Some exploration of further predisposing and
protective factors is also needed.
186
2012. április 12-13.
P/V-5
CONDUCTING CROSS-DISORDER WHOLE-GENOME ASSOCIATION
STUDIES: LIMITATIONS AND SOLUTIONS
Background: Recent advances in biotechnology and genome informatics have opened new windows of
opportunity for psychiatric genetic research. In addition to the publicly available population genetic datasets of
the HapMap Consortium and the 1000 Genomes Project, the Genetic Information Association Network (GAIN)
founded by the National Institues on Health (NIH) has provided controlled access to several neuropsychiatric
whole-genome data, including bipolar disorder, major depression and schizophrenia. Combination of these
datasets yields an excellent opportunity to study whole-genome associations with phenotypes cutting across
diagnostic categories. However, such analysis also comes with issues stemming from the differences in
geographic location of the samplings, genotyping platforms, marker densities and annotations. The goal of this
presentation is to discuss these problems and the possible solutions in details.
Methods: We analyzed the GAIN bipolar (n=2802) and major depression (MDD) case-control datasets
(n=3541) accessed from the National Center of Biotechnology Information (NCBI) database of Genotypes and
Phenotypes (dbGaP). We performed multipoint marker imputation by using IMPUTE2 to reduce the
discrepancies in marker densities and coverages due to different genotyping methods (Affymetrix 6 GW and
Perlegen 600K genotyping chips in the bipolar and MDD data, respectively). The 1000 Genomes Project's 2011.
interim data was used as reference for the imputations. Annotation issues were corrected by using liftOver.
Population stratification was estimated and corrected by using ADMIXTURE. Quality control and haplotype
block structure mapping were carried out by using PLINK.
Results: Although both datasets contained Caucasian subjects' data only, the population stratification were
clearly detectable:3 subpopulations were identified. Marker imputation increased the number of shared markers
from 175,549 to 6,037,982, providing a reasonable coverage for cross-disorder multimarker studies. In
subsequent analyses we plan to search for associations with clinically significant phenotypes, e.g. suicidality in the
combined datasets.
Supervisor: János Réthelyi
187
P/V-6
IS DREAMING MERELY A COGNITIVE PERFORMANCE?
ANALYSIS OF THE CONTENT AND NARRATIVE STRUCTURE OF
CHILDREN’S DREAMS*
Piroska Sándor1, Sára Szakadát2, Orsolya Péntek3, Róbert Bódizs1,2
1
2
3
Department of Cognitive Sciences, Budapest University of Technology and Economics,
Budapest
Institute of Psychology, Károli Gáspár University, Hungary, Budapest
Inspired mainly by the longitudinal studies of Foulkes, the mainstream of developmental psychology considers
dreaming a cognitive performance deriving it solely from childrens’ cognitive abilities. In contrast, the current
neurocognitive approaches see the function of REM sleep and dreaming in the consolidation of emotional
memories and in affective regulation.
This study investigates the ontogeny of dreaming, evaluates the frequency, content and narrative structure of
dreams together with the cognitive and affective development in children.
In our content analysis we followed the rules described by Foulkes, but the method of dream collection was
fundamentally different: instead of interviews after awakening from sleep in the laboratory, over 6 weeks children
would report their dreams at home to their pre-trained parents in the form of tape-recorded dream-diaries based
on provided questionnaires.
The initial content analysis (n=12, age=4-8 years) revealed differences to earlier results: dreams are longer in
every age group compared to the previous findings, self-representation is more frequent (79%), movement (84%)
and living emotions (43%) are common in the dream experience; furthermore the number of dream reports does
not change significantly with age (one dream per week in all age groups).
The current study is a part of a bigger research project, which aims to widen our knowledge about this seldom
investigated field of developmental studies and dream science - evaluating it in a new, emotional developmentcentered context and using different methodology.
*Financial support: Bial Foundation (55/10).
Supervisor: Róbert Bódizs
188
2012. április 12-13.
P/V-7
STUDY OF FEEDBACK-DRIVEN REINFORCEMENT LEARNING IN
SCHIZOPHRENIA
Zsuzsanna Somlai1, Szabolcs Kéri2, 3
1
2
3
National Psychiatry Center, Budapest
Faculty of Medicine, Department of Physiology, University of Szeged, Szeged
Introduction: Several previous studies have attempted to investigate this type of feedback-driven reinforcement
learning in schizophrenia, but the results are heterogeneous and non-conclusive, with some studies showing
impairment and others showing no impairment.
In this study, we explored the clinical predictors of reward- and punishment learning using a probabilistic
classification learning task.
Methods: Participants were 40 patients with schizophrenia (22 outpatients) and 30 healthy control volunteers
with negative psychiatric history. The diagnosis was based on the DSM-IV criteria. All participants received the
International Neuropsychiatric Interview Plus. General functioning was assessed with the GAF scale. Clinical
symptoms were evaluated with the PANSS, The control volunteers were employees and their acquaintances who
were matched with the patients for age, gender, education and were matched for tobacco smoking because
smoking may have an influence on reward-learning.
All participants were administered a computer-based probabilistic classification task. On each trial, participants
viewed one of four images (S1-S4), and were asked to guess whether it belonged to category A or category B.
The STATISTICA 8.0 package was used for data analysis (StatSoft, Inc., Tulsa).
Results: There was no interaction between group and feedback-type (F(1,68)=0.08, p=0.78), suggesting no
differential impairment in schizophrenia for reward- or punishment-learning. When the percentage of optimal
decisions from the reward-learning task was included in a linear regression analysis as a dependent variable, only
the GAF scores emerged as a significant predictor of task performance. When the dependent variable was the
percentage of optimal decision from the punishment-learning task, the significant predictive effect of the GAF
scores was again observed.
Conclusion: The most important finding of this study is that feedback-driven reinforcement learning is
predicted by general psychosocial functioning in patients with schizophrenia, but not by education, PANSS
scores, and chlorpromazine-equivalent doses of antipsychotics.
Supervisor: Szabolcs Kéri
189
P/V-8
EXPERIENCES WITH CHAT COMMUNICATION IN MAINTENANCE
TREATMENT FOR PATIENTS WITH BULIMIC SYMPTOMATOLOGY
Ágnes Mezei1, Hayriye Güleç2, Markus Moessner2, Elisabeth Kohls1, Ferenc Túry1
1
2
Center for Psychotherapy Research, University Hospital Heidelberg, Germany
Keywords: telemedicine, eating disorder, bulimia nervosa
Providing support after treatment termination helps patients to foster recovery or prevent deterioration. An
online program, EDINA, has been developed to fill the gap in maintenance treatment in Hungary for patients
with an eating disorder. It is offered as an aftercare intervention following inpatient or outpatient treatment.
After treatment termination, patients participate in EDINA for 4 months. EDINA has online components of
different intensity, among which group and individual chat sessions are the most intense ones. Participation in
the 90-minute weekly group chat sessions is obligatory. If needed, 30-minute long individual chat sessions can be
booked on a voluntary basis by the participants. Additionally, participants can be invited to book individual chat
sessions in case of severe deteriorations during their participation in the program. A professional counsellor
moderates all the chat sessions.
The efficacy of the program is currently studied in a randomized controlled trial in patients with bulimic
symptomatology in Hungary.
The presentation will evaluate the experiences of the online counsellor in the chat room of the EDINA
Program.So far, registered participants (N=85) have participated in 115 group chat sessions and 20 participants
have utilized 65 individual chat sessions.
The communication in two different modalities of online communication (group versus individual) and the
adaptations in therapeutic processes of the chat environment compared to a face-to-face setting will be
summarized. The challenges of online communication will be highlighted.
Doctoral School: Mental Health Science
190
2012. április 12-13.
P/V-9
AFFECTIVE TEMPERAMENT PROFILE IN PATIENTS WITH
HYPERTENSION. FIRST RESULTS WITH TEMPS-A IN PRIMARY
CARE IN HUNGARY
Ajándék Eőry1, Péter Torzsa1, Xénia Gonda2,3, László Kalabay1, Zoltán Rihmer2
Departmenbt of Family Care Methodology, Semmelweis University, Budapest
Introduction: Affective temperaments profoundly determine emotional reactivity and are the main precursors of
major affective disorders. Having strong genetic and biological basis, they are relatively stable throughout life.
Given the strong and multidimensional relationship between affective and cardiovascular disorders,
temperaments may be effective predictors of future cardiovascular risks and events.
Objectives: The assessment of affective temperament profile of hypertensive patients.
Aims: Explore affective temperaments, anxiety and depression in a hypertensive population in primary care
settings.
Methods: 214 consecutive hypertensive and 90 control subjects completed the Temperament Evaluation of
Memphis, Pisa, Paris and San Diego Autoqestionnaire (TEMPS-A), Hamilton Anxiety Scale (HAM-A) and Beck
Depression Inventory (BDI). For comparisons, Mann-Whitney U test was applied.
Results: Hypertensive patients scored significantly higher in both BDI (U=6854; p=0,002) and HAM-A
(U=6543; p=0,004). Hypertensives also had significantly higher (U=8214; p=0,029) irritable temperament scores,
while there was no significant difference in case of the other temperaments. Controlling for diagnosed depression
rendered the effect of irritable temperament on hypertensives only marginally significant (U=5836; p=0,053).
Conclusions: Our results suggest that BDI and HAM-A could be effectively used in primary care for screening
patients with high cardiovascular risk. The more marked presence of the irritable temperament in the
hypertensive group reveals new information, since it may mediate susceptibility to behavioural risk factors and
reaction to stressful life events known to play a role in cardiovascular risk. Exploration the relationship between
irritable temperament and Type A behaviour needs further studies.
Supervisor: Zoltán Rihmer
191
P/V-10
EFFECTS BETWEEN DONATION ATTITUDE AND DONATION
ACTIVITY IN HUNGARIAN INTENSIVE CARE UNITS
Sándor Mihály
Hungarian National Blood Transfusion Service (HNBTS), Organ Coordination Office (OCO),
Budapest
Introduction: The number of cadaver organ donors is influenced by ICU staffs’ attitude, knowledge, and the
acceptance of brain death (BD) criteria, meanwhile the participation in the donation process influences the
attitude of the involved personnel. The aim of this research is to investigate the Hungarian hospitals, especially
ICU personnel attitude regarding to organ donation.
Method: The survey started on the 27th of May, 2011 with validated questionnaire which contains 46 questions.
The questionnaire was filled based on 98 donor reports, when first signs of BD were identified and family was
approached. Method of data collection was done via personal visits or phone calls. 39 hospitals participated from
17 counties. Descriptive and statistical analysis was also used.
Results: One family interview happened in 45 cases (46%), more in 53 cases. They last for 16-23 minutes in
average (STDEV: 7-32 mins). 87 times one medical doctor (MD), and 11 times two MDs informed the family. 8
of the 17 initial family refusals were changed during the family approach. One communication occurs 1h 33 mins
before the recognition of the first signs of the BD (STDEV: 13:56), while the first started 15h 50 mins before the
recognition of the the BD (STDEV: 23:15), and the last was after the BD identification by 4h 10 mins in average
(STDEV: 11:35).
Discussion: In order to increase the effectiveness of the family approach, it is necessary to learn the
methodology how to communicate with donor families, and to ensure appropriate environment, timing and
input. Further evaluation of family refusals can identify the most common reasons behind refusals, and by
knowing that we can prepare ourselves better for these meetings.
Supervisor: József Kovács
192
2012. április 12-13.
P/VI
Chairman:
Prof. Dr. József Tímár
193
194
2012. április 12-13.
P/VI-1
RTF1 GENE IN CARBOPLATIN RESISTANT OVARIAN CANCER
Zsófia Pénzváltó1, András Lánczky2, Balázs Győrffy3
1
2
3
Research Laboratory of Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest
Background: Protocols containing taxol and platinum derivatives represent the primary treatment options for
ovarian cancer. Biomarkers of therapy response proposed to date did not proved to be robust enough to enter
clinical use.
Purpose: In present study our aim was to identify potential predictive biomarkers of platinum derivatives in an
in vitro model.
Methods: We have built up a databank of publicly available ovarian microarray datasets containing treatment
and response information. ROC (Receiver Operating Characteristic) analysis were performed in R statistical
environment for all genes and then ranked them based on the area under the curve (AUC) values. We identified
the most promising candidates of predictive genes and compared these to available literature. Then, top genes
were selected for in vitro functional validation. In this, gene silencing with simultaneous drug administration was
performed in ovarian cancer cell line OVCAR-3. The success of the RNAi was validated by PCR. The changes in
the cell resistance were measured by CASY cell counter and MTT test.
Results: All together 1152 platinum-treated ovarian cancer patients were identified (average PFS=24.8 months).
The RTF1 gene was capable to discriminate pathological response by high significance (AUC=0.652, p=2.1E-07,
n=816). The silencing of the RTF1 significantly decreased the OVCAR-3 cells resistance to carboplatin (p=0.03).
Conclusion: RTF1 gene expression showed a correlation to pathological response in silico and carboplatin
resistance in vitro. The RTF1 gene is a new biomarker candidate for ovarian cancer chemoresistance.
Program: Oncology
Supervisor: Balázs Győrffy
195
P/VI-2
ß-CATENIN, TRICELLULIN AND EZH2 DIFFERENTIATE FETAL AND
EMBRYONAL COMPONENTS IN EPITHELIAL HEPATOBLASTOMA
Kriszta Schlachter1, Mónika Gyugos1, Gábor Lotz1, Ilona Kovalszky2, Kornélia Baghy2,
Péter Nagy2, Gábor Lendvai1, András Kiss1, Zsuzsa Schaff1
1
Second Department of Pathology, Semmelweis University, Budapest
Budapest
2
Background : Hepatoblastoma (HB) is a rare, but the most common hepatic malignancy of childhood with a
peak incidence from 6 months to 3 years. Histologically, these tumors can be divided into epithelial, mixed and
not specified types. Most cases of HBs are epithelial, consisting of a mixture of fetal and embryonal type tumour
cells.
Aims: HBs derive from the hepatic precursor cells and have several morphologies (small cells, embryonal and
fetal type tumor cells). Since the prognosis of HB is related to its differentiation, we aimed to investigate the
expression pattern of ß-catenin, tricellulin and EZH2 (enhancer of zeste homolog 2) in fetal and embryonal
subtypes using immunohistochemical reactions.
Results: 25 HBs were analyzed, including 12 fetal, 10 embryonal and 3 fetal/embryonal subtypes. Non-
tumorous surrounding liver samples were available in 22 cases. We found no nuclear EZH2 staining in normal
liver samples, while tumor cells displayed high EZH2 expression, with a significantly stronger positivity in the
embryonal component in comparison to the fetal subtype (p=0.003) and normal liver (p<0.001). There were no
significant differences in tricellulin and citoplasmatic ß-catenin expression in the two epithelial subtypes,
nevertheless fetal type cells showed significantly increased expression of tricellulin (p=0.017) and citoplasmatic ßcatenin (p=0.012) when compared with the normal liver. Significantly increased nuclear ß-catenin expression was
observed in the embryonal component compared to the fetal component (p=0.007), in the normal liver there was
no staining.
Conclusions: Our data indicate that increased nuclear ß-catenin and EZH2 expression is associated with the
poorly differentiated tumour components (i.e. embryonal) of HB, while elevated expression of tricellulin and
citoplasmic ß-catenin refers to a well-differentiated phenotype (i.e. fetal).
Acknowledgement: this study was supported by grants OTKA T75468 from the National Scientific Research Foundation and
TÁMOP-4.2.1/B-09/1/KMR-2010-0001 by the National Development Agency of Hungary
Supervisor: Zsuzsa Schaff
196
2012. április 12-13.
P/VI-3
ASSOCIATION BETWEEN THE INCIDENCE OF LYME DISEASE AND
TEMPERATURE IN HUNGARY, 1998-2010
Attila Trájer1, János Bobvos2, Katalin Krisztalovics3, Anna Páldy4
1
2
3
4
National Institute of Environmental Health, Budapest
National Centre of Epidemiology, Budapest
National Institute of Environmental Health, Budapest
The increase of Lyme borreliosis - Lyme disease - (LB) can be expected due to climate change, while the
distribution of the disease depends on the annual activity of ticks and temperature change. We aimed to assess
the temperature dependence of the incidence of the disease in Hungary. The weekly LB data, mandatory
reportable since 1998, were gained from the National Epidemiologic and Surveillance System for the years 1998
to 2010. The daily temperature data were derived from the European Climate Assessment and Dataset. The
association was studied at national level, descriptive statistics and linear regression models were applied. A
significant increasing trend (P=0.0049) was observed in the mean temperature of the analysed years; (0.052oC per
year). The annual LB incidence doubled during the 13 years. The incidence rates of the periods 1998-2001 and
2007-2010 were 11.1 resp. 17.0 per 100,000. The start of steep increase of weekly LB incidence (0.1 per 100,000)
shifted significantly by 3 weeks earlier, the start date of spring showed similar trend (P=0.0041). LB incidence
increased more steadily in spring than in the summer, with 79% of the increase being reported during weeks 1528th with a maximum rate of the increase occurring in weeks 23-25. The trend was significant between the 15th
and the 28th week. In the warmer years with 19.02oC mean temperature of May and June the LB incidence curve
reached the annual peak 2-3 weeks earlier and the descending phase of the curve started earlier than in the colder
years with 17.06oC of the same period.
Program: Oncology
Supervisor: Anna Páldy
197
P/VI-4
TUMOR CELLS AND CARCINOMA-ASSOCIATED FIBROBLASTS
INTERACTION REGULATES MATRIX METALLOPROTEINASES AND
THEIR INHIBITORS IN ORAL SQUAMOSUS CELL CARCINOMA
Alexandra Fullár1, József Dudás2, Ilona Kovalszky1
1
2
Budapest
Department of Otorhinolaryngology, Medical University Innsbruck, Innsbruck, Austria
Introduction: A recently developed co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 oral
squamous carcinoma cells (OSCC), resulted in conversion of normal fibroblasts into carcinoma-associated
fibroblasts (CAFs). Paracrine circuits interacting between OSCC cells and CAFs might regulate the gene
expression and function of matrix remodeling enzymes and their inhibitors.
Methods: Co-culture between SCC-25 cells and PDLs was performed for 7 days, followed by analysis of gene
expression and of gelatinase activity. In some experiments co-cultured cells were treated with 10-6 mol / L
dexamethasone. SCC-25 cells or PDL fibroblasts were treated with IL-1β at 0.015-1.5 ng/ml for 4, 8 and 24
hours.
Results: In co-culture, gene expression of matrix metalloproteinase-1, -2, -3 (MMPs 1-3) was upregulated in
PDLs, and that of MMP-1 and -9 in SCC-25 cells. IL-1β at 1.5 ng/ml upregulated MMP-1 and of MMP-3 in
PDLs, while MMP-2 was regulated by TGFβ1. SCC-25 produced pro- and active MMP-9, whose activity
increased in co-culture. MMP-9 was regulated by fibronectin, via the αvβ6 integrin receptor. Although produced
mainly in PDLs, active MMP-2 was only found at SCC-25 cells. Tissue inhibitors of metalloproteinases (TIMPs) 1 and -3 were significantly upregulated in PDLs during co-culture, in which inflammatory cytokines and the
TGFβ1-pathway were involved.
Conclusion: The gene expression of MMPs and TIMPs is regulated by paracrine circuits between CAFs and
tumor cells, in addition, these cells also share activities in activation of MMP pro-enzymes. The crosstalk between
cancer and the surrounding fibroblast stroma cells is essential in fine regulation of invasivity of cancer cells.
Program: Oncology
Supervisor: Ilona Kovalszky, József Dudás
198
2012. április 12-13.
P/VI-5
MICRORNA EXPRESSION DIFFERS IN EMBRYONAL AND FETAL
SUBTYPES OF EPITHELIAL HEPATOBLASTOMAS
Mónika Gyugos1, Krisztina Schlachter1, Gábor Lotz1, Ilona Kovalszky2, Kornélia Baghy2, Péter
Nagy2, András Kiss1, Zsuzsa Schaff1, Gábor Lendvai1
1
2
Second Department of Pathology, Semmelweis University, Budapest
Budapest
Background and aims: Hepatoblastoma (HB) is the most common primary liver cancer in childhood, which
has epithelial, mixed (epithelial and mesenchymal) and non specified types, based on tissue components. Since
the prognosis of the two epithelial subtypes, embryonal and fetal, is different, we aimed to examine whether these
differences were present at microRNA (miRNA) expression level as well.
Methods: Using macrodissection, total RNA was isolated from 57 formalin fixed paraffin-embedded samples
consisting of 22 fetal, 15 embryonal and 20 non-tumorous surrounding liver samples. Following DNase
treatment, the expression of 16 microRNAs was determined using TaqMan MicroRNA Assays supplied by
Applied Biosystems. For calculating relative expression, the average of miR-140 and miR-328 expressions was
applied as reference, and the statistical differences between the epithelial HB subtypes were analyzed using
Wilcoxon matched pairs test.
Results: In the 25 HB cases, when comparing embryonal and fetal components, we found elevated
expression levels of miR-17-5p, miR-18a, miR-96, miR-210 and miR-224 in the embryonal component.
In relation to non-tumorous surrounding liver samples, decreased miR-17-5p, miR-21, miR-122, miR-210, miR223 and miR-224 levels and increased miR-221 level were observed in fetal subtypes, furthermore decreased miR17-5p and miR-122 levels were found in the embryonal component. The mentioned differences were significant
statistically (p<0.05).
Conclusion: The results indicate that different microRNA expression patterns exist in the studied
hepatoblastoma subtypes. Interestingly, the up- and downregulation of miR-17-5p, miR-21, miR-122, miR-210
and miR-224 in HB differed from that reported in hepatocelullar carcinoma.
Acknowledgement: This study was supported by grants OTKA T75468 from the National Scientific Research Foundation
and TÁMOP-4.2.1/B-09/1/KMR-2010-0001 by the National Development Agency of Hungary
Supervisor: Zsuzsa Schaff
199
P/VI-6
THE ROLE OF DIABETES AND ANTIDIABETIC DRUGS IN
PANCREATIC FIBROSIS AND CANCER
Katalin Kiss1, Gábor Firneisz2, Ilona Kovalszky1
1
2
Budapest
Introduction: Diabetes mellitus is a major public health challenge, and has been linked to a number of cancer
types including pancreatic cancer (PaC). Pancreatic stellate cells (PSC) have an essential role in PaC development
and growth. We hypothesize that PSC can be stimulated by increased glucose concentration corresponding to the
range of a poorly controlled diabetic individual. Potential effects of certain antidiabetic drugs (biguanids, insulin
and GLP-1 mimetic) on PSC activation will also be assessed in vitro.
Aims: First we examined the effect of higher glucose concentration in PSC activation. Then we used antidiabetic
drugs from three agent groups (insulin, biguanid, incretin) on these differently cultured cells. We investigated
whether these treatments had activated the PSCs, namely if the collagen-1 and -3 levels had been elevated in the
cell mediums and in the cells.
Methods: We cultured a human immortalised PSC cell line parallel in normal (5,5 mmol/l) and in elevated (13,5
mmol/l) glucose concentration for three weeks, and used ELISA and RT-PCR to mesure the alteration in
collagen-1 and -3 expression in culture mediums. To assess their effect on cell activation, the following
compounds were added to the cell clones in the last 48 hours: (i) the known PSC activator TGFβ (ii) antidiabetic
drugs: Lantus, phenphormin, Victosa (iii) antidiabetic drugs and TGFβ in combination.
Results: High glucose concentration alone enhanced the production of collagen. This was further increased after
TGFβ exposure. Lantus and phenphormin had no effect. Victosa decreased collagen synthesis and provided
protection against the effect of TGFβ. These effects could be measured on mRNA as well as on protein level.
Conclusion: High glucose concentration activates pancreatic stellate cells and most probably promotes the
development of pancreatic fibrosis, thus, also playing a role in the formation of pancreatic carcinoma. Incretin
type GLP-1 analog antidiabetics appear to inhibit the high glucose induced activation of PSCs.
Program: Oncology
Supervisor: Ilona Kovalszky
200
2012. április 12-13.
P/VII
Chairman:
Dr. István Antal
201
202
2012. április 12-13.
P/VII-1
THE HIGHLY SELECTIVE µ-OPIOID AGONIST PEPTIDE DAMGO
SHOWED PREDOMINANTLY PERIPHERAL ANALGESIA IN RAT
VISCERAL PAIN MODEL
Erzsébet Lackó1, Pál Riba1, Melinda Sobor1, Júlia Timár1, Shaaban A. Mousa2, Michael Schäfer2,
Susanna Fürst1, Mahmoud Al-Khrasani1
1
2
Department of Pharmacology and Pharmacotheraphy, Semmelweis University, Budapest
Department of Anaesthesiology and Intensive Care Medicine, Charité University, Berlin
Aims: The present study was planned to assess the analgesic effects of peripheral versus central administration of
the selective µ-opioid agonist D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAMGO) and morphine in the rat
writhing test.
Methods: Male Wistar rats weighing 100-140g were used. Visceral nociception (abdominal muscle contractions
or simultaneous stretching of at least one hind limb) was induced by intraperitoneal (i.p.) injection of 2% acetic
acid (3ml/kg). Saline or test compounds were injected (i.p. or i.c.v.) 55 min after i.p. acetic acid injections. Then,
a period of 60-80min was chosen to evaluate the analgesic effects of the test drugs.
Results: DAMGO and morphine dose-dependently inhibited the rat visceral nociceptive responses after i.p. or
i.c.v. administration. DAMGO and morphine showed comparable analgesic effects after i.p. injections. On the
other side, DAMGO and morphine showed higher effects after i.c.v. than after i.p. administration, though the
i.p./i.c.v. effective dose ratio for DAMGO was higher than that of morphine. Co-administration of the
quaternary opioid antagonist naloxone methiodide (NAL-M) significantly reversed the antinociceptive action of
i.p. DAMGO and morphine. On the other hand, i.c.v. injections of NAL-M partially reversed the analgesic effect
of. i.p. morphine, but not of i.p. DAMGO. Moreover, i.p. injections of opioid antagonist naloxone totally
diminished the analgesic actions of DAMGO or morphine.
Conclusions: These results indicate that systemic morphine produced visceral analgesia most likely by
activation of both central and peripheral opioid systems. However, the systemic analgesic effect of DAMGO
was based predominantly on the activation of the peripheral opioid system.
Supervisor: Zsuzsanna Fürst
203
P/VII-2
EFFECT OF NATIVE AND OLIGOTUFTSIN CONJUGATED W-SEWSPEPTIDES ON THE ADHESION AND MIGRATION OF TUMOR CELL
LINES
Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest
Tumor progression towards metastasis is a multistage process including local invasion, intravasation, survival
and arrest in the circulation, extravasation and colonization. The detachment of cancer cells from the primary
tumors and their spreading that may also occur during the surgical resection of the primary tumor is
characterized by a high risk of increased migratory ability and decreased adhesion of tumor cells.
The aim of our work was i) to study the W-S-EWS peptides, repetitive elements of extracellular part of the
hematopoietic cytokine receptors as well as ii) their oligotuftsin (OT20) based conjugates as candidate
molecules that are able to simultaneously reduce tumor cell migration and enhance cell adhesion so that they
can decrease tumor cells spreading during surgical removal of primary tumors. For this purpose chemotacitic
responses of a murine (J774.2) and two human cell lines (MM6 and THP-1) were measured in NeuroPorbe®
chamber and their adhesion was analyzed by the xCELLigence (Roche) impedimetric device.
Our results showed that in all three cell lines chemotaxis was significantly influenced by both short peptides
and conjugates, whereas adhesion was significantly modified only by the SEWS tetrapeptide in MM6
(decreased at 10-12-10-6M; increased only at 10-7M). Significant reduction in migratory responses were
observed in the case of EWS, OT20-EWS and SEWS in J774.2 cells as well as with WSEWS and OT20WSEWS in THP-1 cells. OT-20-SEWS in turn acted as chemoattractant on J774.2 cells, as well as SEWS
and OT20-SEWS in THP-1 cells. In MM6 all six molecules except for OT20-EWS promoted migratory
responses.
In conclusion only one conjugate OT20-EWS proved to fulfill criteria (on J774.2 cells) of an optimal tumor
spreading reducing molecule that is the ability to decrease migratory responses and enhance adhesion. In the
following phase of our work we intend to investigate this molecule in vivo using mouse models.
204
2012. április 12-13.
P/VII-3
CHARACTERIZATION OF DRUG CARRIERS SYSTEMS WITH
DIFFERENT HLB VALUES
Department of Pharmaceutics, Semmelweis University, Budapest
The surface active agents consist of a molecule that combines both hydrophilic and lipophilic groups. They are
characterized by the HLB value which is a balance of the size and strengths of these two opposing groups. The
HLB scale ranges from 1 to 20: at lower values lipophilic and at higher values hydrophilic. In the past 60 years
several different experimental and theoretical methods were used to determine the HLB value. However, there
are many of the criticisms of the HLB concept and assays, too. Excipients with characteristic HLB can influence
the main attributes of drug delivery systems such as drug release and stability.
Objectives: The aim of the study was to investigate the physical attributes of potential drug carrier systems
containing pharmaceutical excipients (e.g. Tween 80, Span 80, Gelucires) with characteristic HLB values. Oil in
water emulsion systems were prepared to study the relationships between HLB and particle (drop) size
distribution, turbidity and rheograms. High pressure homogenizer (Avestin, EmulsiFlex B-15) and high shear
mixer (Miccra, Art-Miccra D-8) were used to prepare the emulsions.
Results: The droplet size of emulsions was evaluated by Malvern Master Sizer 2000. In each cases the
distribution curves demonstrated a minimum at the estimated HLB corresponding with the literature data. The
turbidity measured by spectrophotometer (Metertech, SP-8001 UV/Visible Spectrophotometer) was in good
correlation with the required HLB to stabilize the disperse system. The carrier systems demonstrated different
physichochemical characteristics which were related to the HLB values of the excipients.
Supervisor: István Antal
205
P/VII-4
DEVELOPMENT OF A MULTIPARTICULATE DRUG DELIVERY
SYSTEM FOR PETROSELINUM CRISPUM EXTRACT
Zsófia Edit Pápay1, Emese Balogh1, Annamária Kósa2, Ákos Ruszkai, Imre Boldizsár2,
István Antal1
1
2
Semmelweis University, Department of Pharmaceutics, Budapest
Eötvös Loránd University, Budapest
Parsley (Petroselinum crispum L.) is a popular plant which is expected to become a herbal medicine. It’s herb and
seeds are known to be diuretic, smooth muscle relaxant and hepatoprotective. The most important identified
active ingredients are flavonoids, cumarins and vitamin C. Apigenin and its glycosides are the main flavonoids in
parsley, which can be found in the leaves in high quantities. The flavonoid apigenin may have antiinflammatory,
antioxidant and anticancer activities.
Objectives: The objectives of this study were to detemine the total apigenin content of the parsley extract with
liquid chromatography (HPLC) and to develop a carrier system for the extracted ingredients. As carrier system
multiparticulates were applied to load the Petroselinum crispum ethanolic extract in fluid-bed. The critical
parameters of the fluidization were determined. The appearance of pellets were analyzed by stereomicroscopy
and image analysis. The apigenin containing pellets were filled into hard gelatine capsules for better dosing and
their drug release was investigated.
Results: The amount of apiin and its aglycon apigenin in parsley extract were assayed with HPLC method.
According to the results, the extract of 100 g dried parsley contains about 1.4 g apigenin. It is known that the
plant phenolic content is highly affected by the growing conditions and genotype. The physical characteristics of
pellets as well as the drug release from hard gelatine capsules were adequate.
Doctoral School: Pharmaceutical sciences
Supervisor: István Antal
206
2012. április 12-13.
P/VII-5
OPTIMIZATION OF A SIMPLE CAPILLARY ELECTROPHORESIS
METHOD FOR THE SEPARATION OF TWELVE QUINOLONE
DERIVATIVES
Aura Rusu1, Gabriel Hancu1, Gergő Tóth2, Gergely Völgyi2, Béla Noszál2, Árpád Gyéresi1
1
2
University of Medicine and Pharmacy, Department of Pharmaceutical Chemistry, Târgu Mureş
Quinolones are one of the most commonly prescribed antibacterial agents. Due to their broad-spectrum they are
often used against Gram-positive and Gram-negative bacteria. The simultaneous separation of quinolones from a
complex matrix is difficult due to their similar structural and physico-chemical properties.
Aims: The aim of the present study was to elaborate a simple, rapid, efficient and validated capillary zone
electrophoretic (CZE) method for the simultaneous separation of twelve quinolone derivatives and to optimize
the analytical conditions.
Results: A CZE method with diode array UV detection has been developed for the simultaneous determination
of the following molecules: ciprofloxacin hydrochloride (CIP), difloxacin (DIF), 3-methyl-difloxacin (3'M-DIF),
enoxacin (ENO), lomefloxacin (LOM), moxifloxacin hydrochloride (MOX), nalidixic acid (ANA), 8-fluornorfloxacin (8-F-NOR), ofloxacin (OFL), sparfloxacin (SPA), pefloxacin mesylate (PEF) and 8-fluor-pefloxacin
(8-F-PEF). For reliable and reproducible results borax was chosen as background electrolyte (BGE).
The individual electrophoretic mobilities were calculated by Offord equation predicting the optimal separation at
pH 8.5 - 9.5 with appropriate short migration time. 25 mM borax (pH 9.33) at + 20 kV, 25 0C and a silica-fused
capillary of 70 cm length (effective length 62 cm) x 50 μm internal diameter was found as the optimized
condition. The separation of the twelve quinolone derivatives was achieved in less than 10 minutes, the order of
separation being: MOX, SPA, 8-F-NOR, LOM, 3'M-DIF, ENO, CIP, DIF, OFL, 8-F-PEF, PEF and ANA. The
analytical method was then validated: precision (RSD for migration time and peak area), linearity as well as limit
of detection (LOD) and limit of quantitation (LOQ) for each compounds was calculated. It was proved CZE is
an efficient method for the simultaneous screening of a large number of quinolone derivatives.
Doctoral School: University of Medicine and Pharmacy, Târgu Mureş
Program: Pharmaceutical sciences
Supervisor: Árpád Gyéresi
207
P/VII-6
SELECTIVITY PROFILING OF FGF RECEPTOR INHIBITORS
Zsákai Lilian1, Németh Gábor2
1
2
Vichem Chemie Ltd., Budapest
Lately, signal transduction therapies are amongst the most important and intensely developing modern
approaches of the tumour therapies. These therapies are based on selective and targeted protein activity
inhibition. The targets are specific to the given tumour types, and inhibitional effects are caused by small
molecules which can penetrate the cell membrane and selective enough to the given protein. In practice, perfect
selectivity for a protein doesn’t exist, and inhibitors have a certain inhibition profile for similar or partially similar
proteins. Fortunately, this phenomenon turned out to be useful in several cases. This is the case for FGFR
receptor analouges FGFR1, FGFR2, FGFR3 and FGFR4 which are kinases of great interest by having leading
roles in several types of cancer, eg. NSCLC, SCLC.
Our aim was to develop small molecule inhibitors with different FGFR inhibition patterns which means that
each of them inhibit the four FGFRs in a varying degree, preferably inhibiting one of them in a considerably
selective way to the orhers. Our main target was FGFR2.
We characterized almost 100 molecules’ inhibition profile on FGFR1, FGFR2, FGFR3 and FGFR4 by
performing biochemical protein activity assays. The selection for these compunds was partially based on
computaional modeling. We found compounds highly selective for FGFR2 and molecules that inhibit all FGFRs
or selective for a pair or triad of the FGF receptors. Our work continues on cellular viability assays, binding
mode and structure analyses.
Doctoral School: Pharmaceutical sciences
Supervisor: György Kéri
208
2012. április 12-13.
AUTHORS AND TITLES OF ABSTRACTS
(LISTED UNDER THE CORRESPONDING DOCTORAL SCHOOLS)
209
210
2012. április 12-13.
Basic Medicine Doctoral School
E/I-2 LATEST RESULTS OF THE RESPIRATORY ASPECTS OF THE INTERNATIONAL TWIN
STUDY
David Laszlo Tarnoki, Adam Domonkos Tarnoki, Emanuela Medda, Levente Littvay, Zsofia Lazar, Rodolfo
Cotichini, Corrado Fagnani, Maria Antonietta Stazi, Lorenza Nisticó, Pierleone Lucatelli, Emanuele Boatta,
Chiara Zini, Fabrizio Fanelli, Claudio Baracchini, Giorgio Meneghetti, Akos Koller, Janos Osztovits, Gyorgy
Jermendy, István Préda,
Róbert Gábor Kiss, Kinga Karlinger, Agnes Lannert, Giuseppe Schillaci,
Andrea Agnes Molnar, Zsolt Garami, Viktor Berczi, Ildiko Horvath
E/I-3 SOPHISTICATED ARRHYTHMIA DETECTION WITH 256-SLICE CT ALLOWS
DIAGNOSTIC CORONARY ARTERY IMAGING IN PATIENTS WITH ATRIAL FIBRILLATION
CORONARY CT ANGIOGRAPHY WITH 256-SLICE SCANNER IN PATIENTS WITH ATRIAL
FIBRILLATION
Mihály Károlyi, Andrea Bartykowszki, Erik Formanek, Mohammed Muhemin, Csaba Csobay-Novák,
Nándor Pintér, Kálmán Hüttl, György Balázs, Béla Merkely, Pál Maurovich-Horvat
E/I-4 THE ROLE OF MICRORNAS IN RENAL ISCHEMIA-REPERFUSION INJURY
Program: Physiology and pathophysiology of the regulation of fluids and electrolyte homeostasis
E/I-5 ISOLATION AND CULTURE OF RAT BONE MARROW MESENCHYMAL STEM CELLS
E/I-6 CARDIOPULMONARY BYPASS IMPAIRS BRAIN OXYGENATION AS DEMONSTRATED
BY NEAR-INFRARED SPECTROSCOPY
Peter Mukli
Program: Meschanisms of normal and pathologic functions of the circulatory system
E/I-7 PREDICTORS OF CRT-INDUCED LEFT VENTRICULAR REVERSE REMODELING
Vivien Klaudia Nagy, Valentina Kutyifa, Astrid Apor, Csilla Liptai, Eszter Édes, Gábor Széplaki, Béla
Merkely
E/I-8 LATEST RESULTS OF THE CARDIOVASCULAR AND ANTHROPOMETRIC ASPECTS
OF THE INTERNATIONAL TWIN STUDY
Adam Domonkos Tarnoki, David Laszlo Tarnoki, Emanuela Medda, Maria Antonietta Stazi, Rodolfo
Cotichini, Corrado Fagnani, Lorenza Nisticó, Pierleone Lucatelli, Emanuele Boatta3, Chiara Zini, Fabrizio
Fanelli, Claudio Baracchini, Giorgio Meneghetti, Janos Osztovits, Gyorgy Jermendy, István Préda, Róbert
Gábor Kiss, Levente Littvay, Julia Metneki, Tamas Horvath, Kinga Karlinger, Agnes Lannert, Andrea Agnes
Molnar, Zsolt Garami, Pal Bata, Gyorgy Baffy, Giuseppe Schillaci, Viktor Berczi
Program: Cardiovascular disorders: physiology and medicine
211
E/I-9 TWELVE-HOLES GOLD ELECTRODE ABLATION CATHETER PROVED TO BE
EFFECTIVE AND SAFE ALSO AT REDUCED IRRIGATION FLOW RATE
Eszter Mária Végh, Endre Zima, Tamás Szili-Török, Gábor Széplaki, Márta Hubay,
Luc Jordaens, László Gellér, Béla Merkely
E/IV-1 THE FIRST CENTRAL-EUROPEAN CARDIOVASCULAR PREVENTION STUDY BUDAKALASZ HEALTH EXAMINATION SURVEY
Zsolt Bagyura, Zsolt Szelid , Pál Soós, Loretta Kiss ,Béla Merkely
E/IV-2 EFFECTS OF THE BENZODIAZEPINE DERIVATIVE, 5-BDBD ON THE P2X4
PURINERGIC RECEPTOR CHANNEL
E/IV-3 H2S PRECONDITIONING OF THERAPEUTICALLY USED STEM CELLS INCREASES
THEIR SURVIVAL AND EFFICACY IN AN IN VITRO MODEL OF CELL-BASED THERAPY IN
MYOCARDIAL INFARCT
E/IV-4 BILAYER EDGES CATALYZE LIPOSOME BINDING, MOVEMENT AND RUPTURE ON
SOLID SURFACES
Tamás Bozó
E/IV-5 CORONARY INTERVENTION LEADS TO COMPLEMENT ACTIVATION THROUGH
THE ALTERNATIVE PATHWAY
Zsófia Horváth, Dorottya Csuka, Katarina Vargova, Andrea Kovács, Andrea Ágnes Molnár1, Leé
Sarolta,Lilian Varga, Róbert Gábor Kiss, István Préda, George Füst
Program: Clinical and experimental cardiology/ Atherosclerosis
E/IV-6 NANOMECHANICS OF DESMIN FILAMENTS
TWEEZERS
Balázs Kiss, Pasquale Bianco
EXPLORED
WITH
OPTICAL
E/IV-7 REVERSIBLE LOW-FORCE-DRIVEN STRUCTURAL TRANSITIONS IN SKELETAL
MUSCLE TITIN REVEALED BY FORCE-CLAMP OPTICAL TWEEZERS
E/IV-8 DETAILED HEMODYNAMIC CHARACTERIZATION OF ATHLETE’S HEART USING
LEFT VENTRICULAR PRESSURE-VOLUME ANALYSIS IN A RAT MODEL
Attila Oláh, Árpád Lux, Ede Birtalan, László Hidi, Balázs Németh, Béla Merkely, Tamás Radovits
212
2012. április 12-13.
E/IV-9 MEASURMENT OF PLATELET ADHESION USING IMPEDANCE BASED TECHNIQUE
Lívia Polgár
Program: Phisiology and clinics of the heart and coronary diseases
E/IV-10 NANOMECHANICAL MANIPULATION OF MASON-PFIZER MONKEY RETROVIRAL
RNA FRAGMENT WITH OPTICAL TWEEZERS
Melinda Simon, Zsolt Mártonfalvi, Pasquale Bianco, Beáta Vértessy, Miklós Kellermayer
E/IV-11 THE EFFECT OF THE OBSTRUCTIVE SLEEP APNEA ON THE NIGHT-TIME
GLUCOSE VARIABILITY IN PATIENTS WITH THE METABOLIC SYNDROME
Orsolya A. Veber, Andrea Dunai, Rezso Zoller, Zsofia Lendvai, Anett V. Lindner, Istvan Mucsi
circulation
P/I-1 EXAMINATION OF PHOTOSENSITIZER-CELLULAR MEMBRANE MODEL WITH
OPTICAL SPECTROSCOPY METHODS
P/I-2 RED BLOOD CELL DISTRIBUTION WIDTH PREDICTS UNFAVOURABLE OUTCOME
FOLLOWING CARDIAC RESYNCHRONIZATION THERAPY
Annamaria Kosztin, Gabor Szeplaki, Eszter Maria Vegh, Szabolcs Szilagyi, Istvan Osztheimer, Levente
Molnar, Endre Zima, Laszlo Geller, Zoltan Prohaszka, Bela Merkely
P/I-4 ELASTIC, CONTRACTILE AND ENDOTHELIAL PROPERTIES OF HUMAN VEIN
SEGMENTS STORED IN A COMPLEX TISSUE MEDIUM
Anna Monori-Kiss, Gábor Ferenc Molnár, Attila Nemes, Violetta Kékesi, Emil Monos, György László
Nádasy
P/I-5 COMPARISON OF EPITAXIALLY AND SOLUTION-GROWN AMYLOID ß25-35 FIBRILS
Ünige Murvai, Judit Somkuti, Katalin Soós, Botond Penke, László Smeller, Miklós S. Z. Kellermayer
P/I-6 TEMPERATURE-PRESSURE STABILITY AND
PARVALBUMIN
Judit Somkuti, Merima Bublin, Heimo Breiteneder, László Smeller
T-P
PHASE
DIAGRAM
OF
P/I-7 RENAL FUNCTION IS ASSOCIATED WITH RED CELL DISTRIBUTION WIDTH
INDEPENDENT OF IRON DEFICIENCY AND NUTRITIONAL STATUS IN KIDNEY
TRANSPLANT RECIPIENTS
Ákos Ujszászi, Mária Eszter Czíra, Ádám Remport, Csaba Pál Kövesdy, Anna Rudas,
Miklós Zsolt Molnár, István Mucsi
circulation
213
Clinical Medicine Doctoral School
E/II-1 REGULATION OF GENE TRANSCRIPTION BY GLUCOCORTICOID RECEPTOR (GR) Β
ISOFORM
Bence T. Ács, István Likó, Karolina Feldman, Péter M Szabó, Henrietta Butz, Károly Rácz, Attila Patócs
E/II-3 ABSORPTION AND TENSILE STRENGTH OF CELL-COATED SUTURES
E/II-4 DETECTION OF EARLY GLAUCOMATOUS PROGRESSION WITH THE RTVUE
OPTICAL COHERENCE TOMOGRAPH AND SCANNING LASER POLARIMETRY
E/II-5 COLORECTAL CARCINOGENESIS FROM AN EPIGENETIC POINT OF VIEW: WHAT
CAN DNA METHYLATION ADD TO THE BETTER MOLECULAR UNDERSTANDING OF
ADENOMA-DYSPLASIA-CARCINOMA SEQUENCE?
Árpád V. Patai, Orsolya Galamb, Gábor Valcz, Alexanda Kalmár, Árpád Patai, Bálint Péterfia, B Wichmann,
Katalin Leiszter
Kinga Tóth, Andrea Schöller, István Fűri, Barbara Kinga Barták, Zsófia Brigitta Nagy, Sándor Spisák,
Ferenc Sipos, Tibor Krenács, Béla Molnár, Zsolt Tulassay
E/II-7 ANALYZING THE RELIABILITY OF THE SPINAL INSTABILITY NEOPLASTIC SCORE
E/III-1 PH REGULATION DURING AMELOGENESIS – FUNCTIONAL EVIDENCES OF
BICARBONATE TRANSPORT IN HAT-7 AMELOBLAST CELLS
Erzsébet Bori
E/III-2 AMBULATORY ARTERIAL STIFFNESS INDEX IN CHILDREN AFTER KIDNEY
TRANSPLANTATION – CROSS SECTIONAL STUDY
Arianna Dégi, Andrea Kerti, Attila J. Szabó, Péter Sallay, Éva Kis, Orsolya Cseprekál, George S. Reusz
E/III-3 CHANGES IN PHOTOPIGMENT EXPRESSION
MORPHOLOGY IN EARLY DIABETES
Anna Énzsöly, Arnold Szabó, Klaudia Szabó, Ákos Lukáts, János Németh
AND
E/III-4 CLINICOPATHOLOGICAL
METASTASES
Katalin Fábián
Program: Pulmonology
CANCER
214
FEATURES
OF
LUNG
PHOTORECEPTOR
WITH
BRAIN
2012. április 12-13.
E/III-5 POLYMORPHISM OF THE HSD11B1 GENE PROMOTER INFLUENCES BONE
MINERAL DENSITY
Karolina Feldman, Ágnes Szappanos, Zsófia Kövesdi, Miklós Tóth, István Likó, Péter Lakatos, Károly Rácz,
Attila Patócs
E/III-6 POSTCONDITIONING AS A PREVENTION METHOD AFTER LOWER LIMB
ISCHEMIA-REPERFUSION INJURY: REDUCING DAMAGES OF THE LUNG
Dávid Garbaisz, Zsolt Turóczi, Olivér Rosero, Gábor Lotz, Zoltán Rakonczay, László Harsányi, Attila
Szijártó
Program: Clinical and experimental research in angiology
E/III-7 ANTI-INFLAMMATORY EFFECTS OF MOUSE MESENCHYMAL STEM CELLS ON
MICROGLIA
Beáta Hegyi
E/III-8 SIGMA-1 RECEPTOR AGONIST TREATMENT IS PROTECTIVE AGAINST RENAL
ISCHEMIA/REPERFUSION INJURY
Ádám Hosszú, Nóra Fanni Bánki, Zsuzsa Antal , Sándor Kőszegi, László Wagner, Ágnes Prókai, Ádám
Vannay, Veronika Müller, Attila Szabó, Andrea Fekete
E/III-9 NPHS2 P.V290M MUTATION IN LATE-ONSET STEROID-RESISTANT NEPHROTIC
SYNDROME
E/III-10 THE ROLE OF THE SIGMA-1 RECEPTOR IN DIABETIC NEPHROPATHY
Sándor Kőszegi, Bánki Nóra Fanni, Ádám Hosszú, László Wagner, Ágnes Prókai, Ádám Vannay, Tivadar
Tulassay , Andrea Fekete
E/III-11 ACTIVATION OF SMAD 2 AND 3 IN THE INTESTINAL MUCOSA OF PEDIATRIC
PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND IN HT-29 CELL LINES
Kriszta Molnar, Ádám Vannay, Leonóra Balicza-Himer, Apor Veres-Székely, Dolóresz Szabó, Nóra Fanni
Bánki, András Arató
Gábor Veres
E/III-12 THE EFFECTS OF POSTCONDITIONING IN A LONG-TERM PERIOD RAT LIVER
ISCHEMIC-REPERFUSION EXPERIMENTAL MODEL
Rosero Olivér, Ónody Péter, Garbaisz Dávid, Tamás Judith, Kocsis Ibolya, Lotz Gábor, Harsányi László,
Szijártó Attila
215
E/III-13 POSITIONAL IDENTITY OF MURINE MESENCHYMAL STEM CELLS RESIDENT IN
DIFFERENT ORGANS IS DETERMINED IN THE POSTSEGMENTATION MESODERM
Bernadett Sági
E/III-14 BIOMARKERS OF BONE FORMATION AND GUT PERMEABILITY IN LONG-TERM
INFLIXIMAB THERAPY IN PEDIATRIC PATIENTS WITH CROHN'S DISEASE
E/III-15 9-CIS-RETINOIC ACID -INDUCED GENE EXPRESSION ALTERATIONS IN AN
ADRENOCORTICAL CELL LINE
Diana Rita Szabó, Peter M. Szabó, Adrienn Zsippai, Katalin Éder, Attila Patócs, András Falus, Károly Rácz,
Peter Igaz
E/III-16 DIFFERENT ADJUVANT ANTIOXIDANT TREATMENTS IN FATTY LIVER
Viktor Hegedüs, Dénes Kleiner, Kálmán Ditrói, József Prokisch, Hedvig Fébel, Éva Sárdi, Gábor Lotz, Attila
Szijártó, Anna Blázovics
P/III-1 CAN HUMAN DNA ACTIVATE IMMUNE CELLS VIA TLR9?
CYTOKINE PROFILE OF HT-29 CELLS TREATED WITH HUMAN DNA ISOLATED FROM
HUMAN CANCER CELLS
István Fűri, Sándor Spisák, Árpád V. Patai, Ferenc Sipos, Barnabás Wichmann, Orsolya Galamb, Gábor
Valcz, Alexandra Kalmár, Bálint Péterfia, Katalin Leiszter, Kinga Tóth, Andrea Schöller, Barbara Kinga
Barták, Zsófia Brigitta Nagy, Tibor Krenács, Béla Molnár, Zsolt Tulassay
P/III-2 VENULAR DIAMETER REGULATORY ROLE OF THE VASCULAR ENDOTHELIAL
GROWTH FACTOR (VEGF) IN DIFFERENT CONDITIONS OF RAT GINGIVA
Milán Gyurkovics, Zsolt Lohinai, Adrienne Győrfi, Csaba Bodor, Andrea Dorottya Székely, Elek Dinya,
László Rosivall
P/III-3 GENE EXPESSION-BASED ANALYSIS OF COLORECTAL DYSPLASIA-CARCINOMA
TRANSITION
Alexandra Kalmár, Orsolya Galamb, Sándor Spisák, Barnabás Wichmann, Ferenc Sipos, Tibor Krenács,
Kinga Tóth, Katalin Leiszter, Andrea Schöller, István Fűri , Zsófia Brigitta Nagy, Barbara Kinga Barták ,
Zsolt Tulassay, Béla Molnár
P/III-5 INVESTIGATION OF THYMIDYLATE SYNTHASE GENE POLYMORPHISM IN COLON
CANCER PATIENTS
Andrea Schöller, Alexandra Kalmár, Árpád V.Patai, Zsófia Nagy, Barbara Barták, Orsolya Galamb, Sándor
Spisák, Lídia Sréter, Béla Molnár, Zsolt Tulassay
216
2012. április 12-13.
P/III-6 COGNITIVE FUNCTION IN PATIENTS WITH TYPE 1 DIABETES
Barbara Szémán, Géza Nagy, Anna Veres-Székely, Mária Sasvári, Dávid Fitala, Adrienn Szöllősi, Orsolya
Hadarits, Zahra Al-Aissa, Anikó Somogyi
P/III-7 DETECTION OF METHYLATED SEPT9 PERIPHERAL BLOOD SCREENING MARKER
IN BOTH LEFT - AND RIGHT - SIDED COLON CANCER AND COMPARISON TO FOBT AND
CEA
Kinga Tóth, Jürgen Beck, Kerstin Buser, Zsófia Brigitta Nagy, Barbara Kinga Barták, Robert Stöhr,
Henriette Golcher, Vera Schellerer, Zsolt Tulassay, Béla Molnár
Pharmaceutical Sciences Doctoral School
E/VII-4 IN VITRO AND CELLULAR STUDY OF EGFR – C-MET KINASE INHIBITORS IN
NSCLC CELL LINES
Pal Gyulavari, Balint Szokol, Ibolya Kurko, Gyorgyi Bokonyi, Gabor Borbely, Csaba Szantai-Kis, Laszlo
Orfi, Istvan Petak1, Gyorgy Keri, Tibor Vantus
E/VIII-1 INDICATION OF BRAIN PENETRABLE COMPOUNDS IN PLANT EXTRACTS BY
PAMPA-BBB – LC-MS ASSAY
Árpád Könczöl, Ágnes Kéry, Judit Müller, Emília Földes, György T. Balogh
E/VIII-2 PHARMACOLOGICAL REGULATION OF TUMOR CELL ADHESION AND
MIGRATION BY CYTOTOXIC GNRH-III CONJUGATES AND R-DEPRENYL DERIVATIVES
TO PREVENT METASTASIS FORMATION
Eszter Lajkó, Lívia Polgár, Marilena Manea, Gábor Mező, Kálmán Magyar, László Kőhidai
E/VIII-3 IMPACT OF THE AQUATIC POLLUTANT HUMAN PHARMACEUTICALS AND
THEIR MIXTURES ON THE PROLIFERATION AND MIGRATORY BEHAVIOR OF THE
FRESHWATER CILIATE TETRAHYMENA PYRIFORMIS
E/VIII-4
DETERMINATION
AND
STUDY
ON
DOSE
LINEARITY
OF
THE
PHARMACOKINETICS OF M-CHLOROPHENYLBIGUANIDE USING A NEWLY DEVELOPED
HPLC UV AND EC METHOD
Rudolf Laufer, Péter Szegi, Viola Csomor, Kornélia Tekes
E/VIII-5
TRIPODAL ION-BINDING RECEPTORS: SYNTHESIS AND CHARACTERIZATION
217
E/VIII-6 PHARMACOKINETICS OF K203, A BIS-PYRIDINIUM
CHOLINESTERASE REACTIVATOR IN RATS AND BEAGLE DOGS
Zita Pöstényi, Péter Szegi, Balázs Tasnádi
MONO-ALDOXIME
E/VIII-7 OPTIMIZATION PROCESS AND HPLC BEHAVIOR OF SOME NOVEL BISPYRIDINIUM ALDOXIMES
Péter Szegi, Zita Pöstényi, Balázs Tasnádi, Rudolf Laufer, Kamil Kuča
E/VIII-8 CHARACTERIZATION OF OFLOXACIN-CYCLODEXTRIN COMPLEXATION
Gergő Tóth, Réka Mohácsi, Ákos Rácz, Aura Rusu, Péter Horváth, Szabolcs Béni, Béla Noszál
Program: Modern trends in phamaceutical scientific research
E/VIII-9 SAMPLE PRE-FRACTIONATION METHOD FOR ANALYSIS OF GLYCOPROTEINS
FROM HUMAN PLASMA
E/VIII-10
GLUCOSIDES
OF
MORPHINE
CONGENERS:
CHARACTERIZATION
SYNTHESIS
AND
E/VIII-11 CHARACTERIZATION THE EFFECTS OF A NOVEL PKD1 INHIBITOR IN VEGF
SIGNALING PATHWAY ON ENDOTHELIAL CELLS
Attila Varga, Csaba Szántai-Kis, Zoltán Horváth, Zoltán Greff, László Őrfi, György Kéri, Tibor Vántus
P/VII-1 THE HIGHLY SELECTIVE µ-OPIOID AGONIST PEPTIDE DAMGO SHOWED
PREDOMINANTLY PERIPHERAL ANALGESIA IN RAT VISCERAL PAIN MODEL
Erzsébet Lackó, Pál Riba, Melinda Sobor, Júlia Timár, Shaaban A. Mousa, Michael Schäfer, Susanna Fürst,
Mahmoud Al-Khrasani
P/VII-2 EFFECT OF NATIVE AND OLIGOTUFTSIN CONJUGATED W-SEWS-PEPTIDES ON
THE ADHESION AND MIGRATION OF TUMOR CELL LINES
P/VII-3 CHARACTERIZATION OF DRUG CARRIERS SYSTEMS WITH DIFFERENT HLB
VALUES
218
2012. április 12-13.
P/VII-4 DEVELOPMENT OF A MULTIPARTICULATE DRUG DELIVERY SYSTEM FOR
PETROSELINUM CRISPUM EXTRACT
Zsófia Edit Pápay, Emese Balogh, Annamária Kósa, Ákos Ruszkai, Imre Boldizsár,
István Antal
P/VII-6 SELECTIVITY PROFILING OF FGF RECEPTOR INHIBITORS
Zsákai Lilian, Németh Gábor
Mental Health Sciences Doctoral School
E/VI-2 SUBTHRESHOLD PSYCHIATRIC
LONGITUDINAL STUDY
Eszter Anna Bertha
CONDITIONS
IN
CHILD
PSYCHIATRY:
A
E/VI-3 RELATIONSHIP BETWEEN PSYCHOLOGICAL RISK FACTORS AND SOMATIC
FACTORS IN ACUTE CORONARY SYNDROMES
Beatrix Rafael, Piroska Balog
E/VI-4 OBSTETRICAL AND GYNECOLOGICAL CONSEQUENCES OF EATING DISORDERS
E/VI-5 ADVERSE LIFE EVENTS AND SUICIDE RISK IN PEOPLE WITH SCHIZOPHRENIA
Krisztina Kocsis-Bogár, Dóra Perczel-Forintos, Mónika Miklósi
E/VI-6 EFFECTS OF CURRENT ALCOHOL AND TOBACCO CONSUMPTION ON PHYSICAL
AGGRESSION AND ADHD SYMPTOMS AMONG HUNGARIAN ADOLESCENTS
Balázs Matuszka, Erika Bácskai, József Gerevich
E/VI-7 THE EFFECT OF PERCEIVED PARENTAL EFFICACY ON PARENTS’ GENERAL
DISTRESS AFTER THEIR CHILD’S SURGERY
Mónika Miklósi, Elvira Galambosi
E/VI-8 BEHAVIOURAL INHIBITION AND IMPULSIVITY IN ADULT ATTENTION DEFICIT
HYPERACTIVITY DISORDER
Szilvia Papp, László Tombor, Brigitta Kakuszi, Lívia Balogh, Viktória Simon, Pál Czobor
219
E/VI-9 QUANTITATIVE EEG IN ADULT ATTENTION EFICIT/HYPERACTIVITY DISORDER
(ADHD)
László Tombor, Szilvia Papp, Brigitta Kakuszi, Lívia Balogh, Viktória Simon, Pál Czobor
E/VI-10 SUICIDAL BEHAVIOR: PSYCHOLOGICAL AND ETHNICAL DIFFERENCES IN THE
SERIOUSNESS OF DELIBERATE SELF POISONING
Mónika Ditta Tóth, András Székely, Szilvia Ádám, Tamás Zonda, Mária Kopp
E/VI-11 ASSOCIATION BETWEEN LUNAR PHASE AND SLEEP CHARACTERISTICS
Csilla Zita Turányi, András Szentkirályi, Mária Czira, Andrea Dunai, Julianna Szőcs,
Orsolya Véber, Katalin Rónai, Andrea Kelemen, Rezső Zoller, Márta Novák, István Mucsi
E/VI-12 COMORBID FACTORS OF INDIVIDUALS WITH A TENDENCY TO ORTHOREXIA
NERVOSA
Márta Varga, Szilvia Dukay-Szabó, Ferenc Túry, Eric F. van Furth
E/VI-13 VARIANTS IN CATECHOL-O-METHYLTRANSFERASE GENE ARE ASSOCIATED
WITH IMPULSIVITY AND EXECUTIVE FUNCTION: RELEVANCE FOR MAJOR DEPRESSION
Dorottya Pap, Ian M Anderson, JF William Deakin, Gyorgy Bagdy, Gabriella Juhasz
P/V-1 POST-ERROR SLOWING IN PATIENTS WITH ATTENTION DEFICIT/HYPERACTIVITY
DISORDER (ADHD) - A META-ANALYSIS Lívia Balogh , Szilvia Papp , László Tombor, István Bitter, Pál Czobor
P/V-2 THE ROLE OF CYP POLYMORPHISMS IN THE THERAPEUTIC EFFECT AND
ADVERSE REACTIONS OF PSYCHOTROP DRUGS
P/V-3 SUICIDE PREVENTION.
RESPONSIBILITY
Győző Orbán
THE
P/V-4 SOCIO-CULTURAL INFLUENCES
ADOLESCENCE
ldikó Papp, Edit Czeglédi, Ferenc Túry
220
FAMILY
ON
MEMBER'S
BODY
IMAGE
POSSIBILITIES
DISSATISFACTION
AND
IN
2012. április 12-13.
P/V-5 CONDUCTING CROSS-DISORDER
LIMITATIONS AND SOLUTIONS
WHOLE-GENOME
ASSOCIATION
STUDIES:
P/V-6 IS DREAMING MERELY A COGNITIVE PERFORMANCE?
ANALYSIS OF THE CONTENT AND NARRATIVE STRUCTURE OF CHILDREN’S DREAMS*
Piroska Sándor, Sára Szakadát, Orsolya Péntek, Róbert Bódizs
P/V-7 STUDY OF FEEDBACK-DRIVEN REINFORCEMENT LEARNING IN SCHIZOPHRENIA
Zsuzsanna Somlai, Szabolcs Kéri
P/V-8 EXPERIENCES WITH CHAT COMMUNICATION IN MAINTENANCE TREATMENT FOR
PATIENTS WITH BULIMIC SYMPTOMATOLOGY
Ágnes Mezei, Hayriye Güleç, Markus Moessner, Elisabeth Kohls, Ferenc Túry
P/V-9 AFFECTIVE TEMPERAMENT PROFILE IN PATIENTS WITH HYPERTENSION. FIRST
RESULTS WITH TEMPS-A IN PRIMARY CARE IN HUNGARY
Ajándék Eőry1, Péter Torzsa1, Xénia Gonda2,3, László Kalabay1, Zoltán Rihmer2
P/V-10 EFFECTS BETWEEN DONATION ATTITUDE AND DONATION ACTIVITY IN
HUNGARIAN INTENSIVE CARE UNITS
Sándor Mihály
Sport Sciences Doctoral School
E/IV-12 THE ATHLETE’S HEART
Zsuzsanna Major, Zsuzsanna Kneffel, Tímea Kováts, Eszter Csajági
Program: Training and adaptation
E/IV-13 DIFFERENT MITOCHONDRIAL BIOGENESIS TO EXERCISE TRAINING IN LOW
AND HIGH EXERCISE RESPONDER RATS
Orsolya Marton, Erika Koltai, Ferenc Torma, Steven Britton, Lauren Koch, Zsolt Radák
Program: Physical training, regulation, metabolism
„János Szentágothai” Neurosciences Doctoral School
E/V-1 PROTEIN-PROTEIN INTERACTIONS REGULATE THYROID HORMONE ACTIVATION
221
E/V-2 FASTING-INDUCED ALTERATIONS IN THE Α-MSH- AND AGRP-IMMUNOREACTIVE
INNERVATION OF TRH-SYNTHESIZING NEURONS IN THE HYPOTHALAMIC PVN
Andrea Kádár, Edith Sanchez, Balázs Gereben, Ronald M. Lechan, Csaba Fekete
E/V-3 A REDUCTION IN THE ACTIVITY OF ALPHA-KETOGLUTARATE DEHYDROGENASE
COMPLEX DECREASES MATRIX SUBSTRATE-LEVEL PHOSPHORYLATION AND PROMPTS
RESPIRATION-IMPAIRED MITOCHONDRIA TOWARDS EXTRAMITOCHONDRIAL ATP
CONSUMPTION
Gergely Kiss, Csaba Konrád, Anatoly A. Starkov, Hibiki Kawamata, Giovanni Manfredi, Steven F. Zhang,
Gary E. Gibson, M. Flint Beal, Vera Adam-Vízi, Christos Chinopoulos
E/V-5 AGING-COINCIDES WITH MORPHOLOGICAL ALTERATIONS OF KISSPEPTIN AND
NEUROKININ B NEURONS IN THE INFUNDIBULAR NUCLEUS OF THE HUMAN MALE
Csilla S. Molnár, Barbara Vida, Máté Sipos, Imre Kalló, Philippe Ciofi, Beáta Borsay, Stephen R. Bloom,
Mohammad A. Ghatei, Waljit S. Dhillo, Zsolt Liposits1, Erik Hrabovszky
E/VII-5 ABSENCE OF CA2+-INDUCED MITOCHONDRIAL PERMEABILITY TRANSITION BUT
RESENCE OFBONGKREKATE-SENSITIVE NUCLEOTIDE EXCHANGE IN C. CRANGON AND
P. SERRATUS
E/IX-9 CONNECTIONAL HIERARCHY IN THE PRIMARY SOMATOSENSORY CORTEX OF
PRIMATES
Maria Ashaber, Emese Pálfi, Cory Palmer, Orsolya Kantor, Robert M. Friedman, Anna W. Roe, Laszlo
Négyessy
E/IX-10 LAMINAR ANALYSIS OF THE SLOW CORTICAL RHYTHM
SOMATOSENSORY CORTEX UNDER KETAMINE/XYLAZINE ANESTHESIA
Richárd Fiáth, Bálint Péter Kerekes, György Karmos, István Ulbert
IN
RAT
E/IX-11 CENTRAL AMYLIN IS A NOVEL NEUROPEPTIDE WITH POTENTIAL MATERNAL
FUNCTIONS IN RAT
P/II-1 NMDA RECEPTORS IN GABAERGIC SYNAPSES DURING POSTNATAL
DEVELOPMENT
Csaba Cserép, Eszter Szabadits, András Szőnyi, Masahiko Watanabe, Tamás F. Freund, Gábor Nyiri
222
2012. április 12-13.
P/II-2 POSTERIOR THALAMIC TIP39 NEURONS PROJECT TO THE
HYPOTHALAMUS AND REGULATE PROLACTIN SECRETION IN MOTHERS
Melinda Cservenák, Ibolya Bodnár, György M. Nagy, Ted B. Usdin, Miklós Palkovits,
Árpád Dobolyi
Program: Neurosciences and cell biology
MEDIAL
P/II-3 OPTOGENETIC APPROACH FOR INVESTIGATION OF NEURONAL MATURATION
Tímea Kőhidi
P/II-4 ALTERED DEVELOPMENT OF HYPOTHALAMUS IN INTRAUTERINE UNDER
NOURISHED RATS MAY CONTRIBUTE TO METABOLIC DISORDERS IN ADULTHOOD
P/II-5
PHARMACOGENOMICAL
SIGNIFICANCE
OF
MITOCHONDRIAL
SUBSTITUTIONS
Program: Clinical neuroscience
DNA
Molecular Medicine Doctoral School
E/VII-1 MODULATION OF EXPERIMENTAL MODELS OF AUTOIMMUNITY BY
Borbála Aradi, Krisztina Pálóczi, Petra Misják, Bence György, Tamás G Szabó, Ágnes Kittel, Szilvia Bősze,
Kata Horváthi, Krisztina Holló, Katalin Szabó-Taylor, Mária Pásztói, András Falus, Edit I. Buzas
E/VII-2 INQUIRING ABOUT AVIAN THYMIC DENDRITIC CELLS
Ildikó Bódi
E/VII-3 ASSOCIATION AND MOLECULAR ANALYSIS OF THE WFS1 GENE
Zsuzsanna Elek
E/VII-6 IKZF1 AND ARID5B GENE POLYMORPHISMS INFLUENCE THE SUSCEPTIBILITY TO
CHILDHOOD ACUTE LYMPHOID LEUKEMIA
Orsolya Lautner-Csorba, Ágnes F. Semsei, András Gézsi, Nóra Kutszegi, András Falus,
Csaba Szalai
E/VII-7 INVESTIGATION OF THE MIRNA BINDING SITE POLYMORPHISMS OF THE SNAP25 GENE
223
E/VII-8 REGULATION OF CASKIN1 SCAFFOLD PROTEIN BY EPHB1 TYROSINE KINASE
Szabolcs Pesti, Annamária Balázs, Beáta Szabó, László Buday
E/VII-9 EFFECT OF EGCG ON MICROSOMAL CORTISOL PRODUCTION
Péter Szelényi
P/IV-2 A NOVEL BURSAL STEM CELL ANTIGEN: CHARACTERIZATION AND ONTOGENIC
STUDY
Nóra Fejszák
P/IV-5 MISPLACED PHOTORECEPTORS DURING POSTNATAL DEVELOPMENT IN THE RAT
RETINA
P/IV-6 META-ANALYTIC COMPARISON OF PROTEOMIC DATA ON EXTRACELLULAR
VESICLE SUBSETS
Tamás G. Szabó, Petra Misják, Borbála Aradi, Bence György, Mária Pásztói, Zsuzsanna Pál, Krisztina
Pálóczi, Valéria László, Éva Pállinger, Erna Pap, Ágnes Kittel, K. Taylor-Szabó, György Nagy, András
Falus, Edit Buzás
Pathological Sciences Doctoral School
E/V-6 ALTERNATIVE SPLICING OF EGFR ECD IN HUMAN MELANOMA
Eleonóra Imrédi
Program: Oncology
E/V-7 miRNA EXPRESSION PROFILE OF ADENOID CYSTIC CARCINOMA OF SALIVARY
GLANDS AND THE BREAST: PRELIMINARY RESULTS
Orsolya Kiss, Anna-Mária Tőkés, Sándor Spisák, Eszter Gábori, Anikó Bata, Subramanian Kumar, Borbála
Székely, Attila Marcell Szász
Janina Kulka
E/IX-1 CHANGES OF miRNA EPRESSION PATTERN DURING THE HUMAN MELANOMA
PROGRESSION
Program: Experimental oncology
E/IX-2 ANGIOGENESIS IS CHALLENGED IN EXPERIMENTAL BRAIN METASTASES
Program: Oncology
224
2012. április 12-13.
E/IX-3 HEPATOCARCINOGENESIS IN MATRILIN-2 KNOCK OUT MICE
Alexandra Fullár, Kornélia Baghy, Ferenc Deák, Bálint Péterfia, Zsuzsa Schaff, József Dudás, Ibolya Kiss,
Ilona Kovalszky
Program: Oncology
E/IX-4 ONCOGENIC MUTATION DEPENDENT EFFECT OF PRENYLATION INHIBITION IN
MELANOMA CELLS
Tamás Garay, István Kenessey, Éva Juhász, Andrea Réti, Viktória László, Judit Dobos, Violetta Piurkó,
Walter Berger, József Tóvári, József Tímár, Balázs Hegedűs
Program: Oncology
E/IX-5 GENETIC AND EPIGENETIC EXAMINATION OF THE SMARCB1/INI1 GENE IN
EPITHELIOID SARCOMA
Gergő Papp
Program: Oncology
E/IX-6 EXAMINATION OF TARGETED SNP VARIANTS IN SIX GENES WITH POSSIBLE
EFFECT ON ADULT CRANIAL SUTURE SYNOSTOSIS
Katalin Wolff, Zoltán Vas, Éva Hadadi
Program: Public health and health sciences
E/IX-7 ANTIVIRAL EFFECTS OF A FERMENTED WHEAT GERM EXTRACT (AVEMAR), IN
THE FELINE AIDS MODEL
Balázs Stercz
Program: Alterations of cells, fibres and extracellular matrix. Diagnosztic pathomorphological studies int he
course of heart and vascular diseases and incertain tumours. Experimentsl and diagnostic
pathomorphological studies
E/IX-8 mTORC1 AND C2 EXPRESSION IN HUMAN COLON CANCER
Tamás Sticz, Anna Sebestyén, Ágnes Márk, Melinda Hajdu, Tamás Micsik, Noémi Nagy, László Kopper
Program: Oncology
P/VI-1 RTF1 GENE IN CARBOPLATIN RESISTANT OVARIAN CANCER
Zsófia Pénzváltó, András Lánczky, Balázs Győrffy
Program: Oncology
P/VI-2 ß-CATENIN, TRICELLULIN AND EZH2 DIFFERENTIATE FETAL AND EMBRYONAL
COMPONENTS IN EPITHELIAL HEPATOBLASTOMA
Kriszta Schlachter, Mónika Gyugos, Gábor Lotz, Ilona Kovalszky, Kornélia Baghy, Péter Nagy2, Gábor
Lendvai, András Kiss
Zsuzsa Schaff
P/VI-3 ASSOCIATION BETWEEN THE INCIDENCE OF LYME DISEASE AND TEMPERATURE
IN HUNGARY, 1998-2010
Attila Trájer, János Bobvos, Katalin Krisztalovics, Anna Páldy
Program: Oncology
225
P/VI-4 TUMOR CELLS AND CARCINOMA-ASSOCIATED FIBROBLASTS INTERACTION
REGULATES MATRIX METALLOPROTEINASES AND THEIR INHIBITORS IN ORAL
SQUAMOSUS CELL CARCINOMA
Alexandra Fullár, József Dudás, Ilona Kovalszky
Program: Oncology
P/VI-5 MICRORNA EXPRESSION DIFFERS IN EMBRYONAL AND FETAL SUBTYPES OF
EPITHELIAL HEPATOBLASTOMAS
Mónika Gyugos, Krisztina Schlachter, Gábor Lotz, Ilona Kovalszky, Kornélia Baghy, Péter Nagy, András
Kiss, Zsuzsa Schaff,
Gábor Lendvai
P/VI-6 THE ROLE OF DIABETES AND ANTIDIABETIC DRUGS IN PANCREATIC FIBROSIS
AND CANCER
Katalin Kiss, Gábor Firneisz, Ilona Kovalszky
Program: Oncology
Doctoral School, Szeged University
E/I-1. TRANSIENT OUTWARD POTASSIUM CURRENT IN DOG ATRIAL PREPARATIONS
Claudia Corici, Zsófia Kohajda, Attila Kristóf, Tamás Szél, Zoltán Husti, István Baczkó, András Varró,
László Virág , Norbert Jost
E/II-6 INVESTIGATION OF TRANSPORTER INTERACTIONS OF ANTIMALARIALS IN VITRO
Péter Szerémy, Ildikó Makai, Márton Jani, Marton Lívia, Szilvia Gedey, Katalin Jakab, János Márki-Zay,
Péter Krajcsi
E/VI-1 BEHAVIOURAL-EPIDEMIOLOGICAL ANALYSIS OF ADOLESCENTS’ SMOKING IN A
POPULATION OF A SMALL TOWN BETWEEN 2008 AND 2010
Mate A. Balazs, Bettina F. Piko
University of Szeged
E/VII-10 SWITCHING ON RNA SILENCING SUPPRESSOR ACTIVITY BY REMODELING THE
ARGONAUTE BINDING DOMAIN
Program: Immunology
P/I-3 THE EFFECT OF OBESTATIN ON BEHAVIORAL RESPONSES INDUCED BY MORPHINE
WITHDRAWAL IN MICE
Nándor Lipták, Roberta Dochnal, Krisztina Csabafi, Júlia Szakács, Gyula Szabó
Program: Psysiological and pathological functions of the neuroendocrine system
226
2012. április 12-13.
P/IV-1 THE COMPACT MUTATION OF MYOSTATIN CAUSES SKELETAL MUSCLE
HYPERPLASIA
P/IV-3 EFFECT OF THE COMPACT MUTATION ON THE GLYCOGEN CONTENT OF
SKELETAL MUSCLE
Doctoral School, Eötvös Lóránd University
E/II-2 THE MYCOBACTERIAL DUTPASE: BIOCHEMISTRY, PHYSIOLOGY AND
MOLECULAR INTERVENTION
Rita Hirmondo, Ildiko Pecsi, Anna Lopata, Amanda C.Brown, Tanya Parish, Beata G. Vertessy, Judit Toth
Program: Structural biochemistry
P/IV-4 EFFICIENCY OF TRANSFECTION ALONG THE REGENERATING SOLEUS MUSCLE
Doctoral School, University of Medicine and Pharmacy, Târgu Mureş
P/VII-5 OPTIMIZATION OF A SIMPLE CAPILLARY ELECTROPHORESIS METHOD FOR THE
SEPARATION OF TWELVE QUINOLONE DERIVATIVES
Aura Rusu, Gabriel Hancu, Gergő Tóth, Gergely Völgyi, Béla Noszál, Árpád Gyéresi
Hungarian Academy of Sciences, Young Researcher Fellowship
E/V-4 MONOCARBOXYLATE-TRANSPORTER-8 AND TYPE 3 DEIODINASE IN AXON
TERMINALS OF THE MEDIAN EMINENCE ALLOW SYSTEM-SPECIFIC REGULATION OF
T3-ACTION IN HYPOTHALAMIC HYPOPHYSIOTROPIC NEUROSECRETORY NEURONS
Petra Mohácsik, Imre Kalló, Barbara Vida, Anikó Zeöld, Zsuzsanna Bardóczy, Erzsébet Farkas, Andrea
Kádár, Antonio C. Bianco, Zsolt Liposits , Csaba Fekete, B Gereben
Semmelweis University, graduate student
P/III-4 RENIN-ANGIONTENSIN-ALDOSTERONE-SYSTEM BLOCKERS IN DIABETIC
NEPHROPATHY: THE ROLE OF THE SIGMA-1 RECEPTOR
Lilla Lénárt, Bánki Nóra Fanni Bánki, Ágota Vér, László Wagner, Ágnes Prókai, Sándor Kőszegi, Ádám
Hosszú, Attila Szabó, Andrea Fekete
227
JEGYZET
228

Program - Semmelweis Egyetem

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