ROMANIAN BALNEARY POTENTIAL

Transcription

ROMANIAN BALNEARY POTENTIAL
Bucharest, September 2012
ROMANIAN BALNEARY
POTENTIAL
Delia Cinteza
Constantin Munteanu
NATIONAL INSTITUTE OF RHEABILITATION, PHYSICAL MEDICINE AND BALNEOCLIMATOLOGY
ROMANIAN ASSOCIATION OF BALNEOLOGY
NATIONAL INSTITUTE OF RHEABILITATION, PHYSICAL MEDICINE AND BALNEOCLIMATOLOGY
Research Department
BRIEF HISTORY OF ROMANIAN BALNEOLOGY
National Institute of Rehabilitation, Physical Medicine and
Balneoclimatology was established in 1924 as "Institute of
Balneology" through sustained endeavor of personalities of the time medical and non-medical: the Ministry of Health, Red Cross,
Romanian Patriarchy, the Ministry of Defense and other institutions.
To note that at that time was the second institute of its kind in
Europe (after that from France).
MEDICAL USES OF NATURAL THERAPEUTIC
Specialists in rehabilitation, physical medicine and
balneology are involved in treating specific deseases
generating functional impairments:
a) traumatic disorders;
b) musculoskeletal disorders;
c) inflammatory rheumatic diseases;
d) cardiovascular disease;
e) respiratory diseases;
f) gynecological diseases;
g) dermatological;
h) neurological disorders;
i) neuropsychomotor disease;
Geological and hydrological surveys on
natural therapeutic resources
Geological
research
is
completed by synthesis materials
(studies, reports, etc.) together
with cartographic materials.
Based on the conclusions of these
materials we obtain detailed
economic
knowledge
to
capitalize therapeutic mineral
resources.
BIOCLIMATIC STUDIES
Working procedure for bioclimatic research refers to
processing specialized climate and microclimate data, leading
to value estimation of bioclimatic indices. Among these
factors are mentioned:
-Thermal comfort index (based on actual temperature
equivalent, determined using temperature, humidity, and
wind intensity);
- Skin climatic stress index (on feeling hot / cold felt by the
human body, depending on air temperature and wind
intensity);
- Lung climate stress index (based on the feeling of hydration
/ dehydration of the lung lining, depending on water vapor
pressure of the atmosphere);
-Total bioclimatic stress index (summing the values of the two
previous climate stress).
- Other bioclimatic indices as air ionisation, etc.
Physico-chemical analysis of
natural therapeutic factors
Quality of natural factors is
determined by their effective physicochemical properties: mineral or
organic composition, gases dissolved,
suspended particles, living organisms.
Microbiological analysis of natural therapeutic
factors
Microbiological
analysis
of
different samples is done for preventive,
diagnostic, prognostic or therapeutic aim.
Biologist working in a microbiology
laboratory is responsible for correct
sampling, laboratory analysis of the
sample, validation of results and
confrontation with complementary data
(clinical, epidemiological and so on), thus
indirectly participated in interpreting the
results .
Physiological and pharmacodynamics research
Knowledge of general problems
concerning the effects of natural factors,
location and their mechanism of action, is of
fundamental importance for a rational
therapy.
The biological activity of natural factors
requires an initial interaction of their
chemical or physico-chemical components
with molecules of living matter. The
primary action at the molecular level,
triggers a complex reaction, resulting overall
pharmacological global effect.
Pharmacodynamic effect is the result of
complex reactions triggered in the body of
the primary action. A drug does not create
new functions in the body, but only
accelerates
or
reduces
disturbed
physiological processes.
ADVANCED RESEARCH AT CELLULAR AND
MOLECULAR LEVEL
The in vitro studies allows
evaluation of cell morphology, protein
synthesis, secretion of certain substances,
cell metabolism, cellular receptors
interaction with different ligands, uptake
or release of electrolytes or other types of
substances that reach the cellular
environment.
Assessing changes at cellular and
molecular level can be achieved by
optical microscopy studies, for cell
morphology, cell viability studies,
immunohistochemistry studies, proteomic
studies carried out by techniques
including electrophoresis and Western
blotting, determination of the biochemical
parameters in the culture media, cell
physiology studies, studies on cellular
senescence, cell signaling studies.
LDH
30
25
0,04
CREATININA
0,03
20
0,02
15
10
0,01
5
0
0
1
1
40
30
20
2
3
4
5
6
2
3
4
S1
7
8
5
6
7
8
9
FOSFATAZA
ALCALINA
S1
9
UREE
2.5
2
1 .5
1
10
0 .5
0
0
1
2
3
1
4
5
6
2
S1
7
8
3
4
9
5
6
7
S1
8
3
2,5
2
1,5
1
0,5
0
1
2
3
4
S1
5
6
7
8
9
12345678
Fig. 193- Analiza imunoblot a
9
expresiei GSK-3β în culturile
gliale de 14 zile
23
1
4
0,1
21
20
7
5
0,0
12
9
6
10
11
8
0,2
0,3
1415
16
13
0,4
0,5
19
22
17 18
0,6
0,7
0,8
0,9
Ligand A
Wnt
inositol
IP3
IMPase
-
IP
PIP2
IMPase
-
IP2
γ
β
α
D M
A U
G N
C
+
Ca2+
PI-3K
Frizzled
+
APC
PI
CMP-PA
PLC
+
AXIN
+
+
Li
PKC
Akt/PKB
Dsh
-
PP2A
- - GSK-3β
GBP
Li
+
P
Phosphorylation, Translocation of
transcription factors
β-catenin
Lithium-Responsive
Gene Network
Regulation of PKC
responsive genes
SYNAPTIC FUNCTION
Long-term Lithium
Effects
NEUROPLASTICITY
β-catenin
Protein degradation
β-catenin
TCF/LEF
TCF/LEF responsive
genes
NEUROPROTECTION
9
ADVANCED RESEARCH AT CELLULAR AND
MOLECULAR LEVEL
ADVANCED RESEARCH AT CELLULAR AND
MOLECULAR LEVEL
Clinical studies for testing therapeutic efficacy of natural
factors
Selection and recruitment of
suitable study participants - time
sensitive consultation is likely to be
longer than in normal situations.
The concept of obtaining informed
consent is considered the basic
principle of GCP.
Integrated Model of curative spa
takes place under experimental and
clinical research conducted, leading
to a scientific background, biological
and medical updated, achieved by
modern experimental techniques and
clinical trials.
“turismul de tratament si cura balneara actioneaza ca factori
sociali cu efecte multiple in special in beneficiul intregii
societati
…
…
…
…
…
satisfacerea necesitatilor si preferintelor de odihna ale diferitelor
segmente de consumatori
redobandirea sanatatii
profilaxia unor boli
cresterea randamentului muncii
reducerea zilelor de concediu medical”
Citam aceasta apreciere deoarece o consideram ca fiind foarte
potrivita pentru strategia propusa in dezvoltarea turismului
balnear din Romania.
Comisia Canadiana de Turism
Factorii terapeutici naturali
…
…
…
…
apele minerale terapeutice
lacurile şi nămolurile terapeutice
gazele terapeutice
ansamblul elementelor fizico-chimice al
principalelor tipuri de bioclimă din România,
inclusiv la nivelul grotelor şi salinelor
Factorii terapeutici naturali
…
…
…
Factori cu efect asupra sanatatii umane si functiilor
organismului, cu valoare terapeutică dovedită ştiinţific
şi recunoscute ca eficiente terapeutic
Se supun rigorilor care reglementeaza doze de
administrare, indicatii si contraindicatii, stabilite prin
studii
Sunt prescrisi in scop profilactic sau curativ de catre
medic si aplicati de catre personal medical calificat
Cercetarea stiintifica
a factorilor
terapeutici naturali
Sursele de factori
terapeutici naturali
Potentialul
balnear al
Romaniei
Exploatarea si
valorificarea
factorilor terapeutici
naturali
Experienta si traditia
potential
…
Efect asupra sanatatii
…
Tipuri de cura
…
Tipuri de ape
…
Caracteristicile surselor
efectul asupra sanatatii
DOVADA EFICACITATII
…
9
9
9
…
Cercetarea stiintifica
Studii de tip cercetare fundamentala si experimentala
pentru stabilirea indicatiilor terapeutice
Studii clinice de atestare / reatestare a calitatilor
terapeutice
Studii de stabilitate
Indicatori de calitate – specifici pentru fiecare tip de
factor
efectul asupra sanatatii
DOVADA SIGURANTEI (lipsa efectelor
nocive)
…
9
9
9
Cercetarea stiintifica
Limitele concentratiei in substante minerale
considerate terapeutice
Limitele concentratiei in substante considerate cu
potential nociv
Substante interzise
Physical, chemical and microbiological
studies of the natural health factors
…
…
Dynamic changes of physical, chemical and microbiologic
characteristics of the mineral sources in Herculane Health
resort
Madalina Ciocan1, Liana Ionescu1, Gh. Gheorghievici, I.Gogâltan2,
Mariana Bujor; 1Institutul National de Recuperare, Medicina Fizica
si Balneoclimatologie; 2S.C. Hercules S.A.; The National Conference of
Balneology, Covasna, 2006
…
Variatia hidrogenului sulfurat si a ionului sulfuric
Period
of follow-up: 1986-2004
Variatia hidrogenului sulfurat si a ionului sulfuric
(mg/l) pentru sursa hidrominerala Neptun I+IV Baile Herculane
(mg/l) pentru sursa hidrominerala Neptun I+IV Baile Herculane
120
120
100
Hidrogen
sulfurat
Ion sulfuric
80
60
40
Hidrogen
sulfurat
Ion sulfuric
80
60
40
20
0
100
20
1988 1994 1995 1996 2004 2006
0
1988 1994 1995 1996 2004 2006
Conclusions:
™Thermal water sulfur
containing
™No significant
variation of mineral
compounds
™No microbiologic
pollution indicators
Physical, chemical and microbiological
studies of the natural health factors
Research on a salt mine climate
characteristics (Slanic Prahova
Unirea salt mine)
Simionca I, Hoteteu M, Enache L, Buturugă
A, Ursaciuc C, Munteanu A, Georgescu I,
Rogojan R
SALT COMPOUNDS
NaCl
97,12–97,32
MgCL2
0,04
CaSO4
1,57–1,64
substance insoluble
1,03–1,16
umiditatea
0,08.
Objectives:
To evaluate the physical, chemical and
microbiological characteristics of the salt
mine climate with possible therapeutic role
Ions
concentratio
n at the zero
level
Ions concentration on different
arias
n- / cm³
367
266
286
184
n+ / cm³
245
204
143
122
Polarity
coeficient
polaritate (n+/n)
0,67
0,77
0,50
0,66
Total
concentration
612
477
409
306
Ions polarity
Entrance
Ventilatio
n aria
Results:
Physical characterization
…
Stable temperature:11,6 – 12,8°C
…
Umidity: ~ 50 – 52 %.
…
Atmospheric pressure = + 18 mmHg.
…
Wind: undetectable
treatme
nt aria
Experimental studies on animals
…
Dej and Cacica salt mines microclimate
influence on Wistar white rats - M. Hoteteu,
Ghe. Simionca, C. Munteanu, L. Enache
Objective:
to determine the effect of underground microclimate
from Cacica and Dej salt mines on protein
metabolism and hidroelectrolyte balance in
different age Wistar white rats with induced
pathology
Conclusions
Tthe speleotherapy cause a variation of the serum
protein
factors,
depending
on
the pathology and used salt mine.
Experimental
cure
normalize
hydric
and
electrolyte balance parameters in most
cases of rats with induced pathologies due to the
direct effect of salt microclimate on the wounds
and burns, and also due to saline load of the
body in the presence of NaCl aerosol.
80 young and adult Wistar white
rats
sensibilized
with
induced
allergic pathology by ovalbumine or
skin pathology (wounds, burns)
divided in experimental and control
groups.
‰The rats from experimental groups
were subjected to a speleotherapy
cure in Ocna Dej or Cacica salt mines
‰
Parameters: total protein concentration,
serum protein electrophoresis, water
volume (ml/24 h) and the amount of
sodium intake (mEq/24 h), urine volume
(ml/24 h) and concentrations of sodium
and potassium in urine (mEq/24 h), the
urinary Na/K ratio as an expression of
the mineralocorticoid response of
adrenals in the experimental conditions.
Exploration of the speleotherapeutic potential through the
cellular and molecular biology techniques
Munteanu C., Munteanu D., Simionca I., Cinteza D., Hoteteu M.;
Abstract
Objective: Exploring the speleotherapy effects on
morphology and physiology
of dermal and pulmonary
fibroblast obtained from Wistar rats tissue in normal
conditions and after induction of experimental “astma”
awareness with ovalbumin.
Materials and methods:
Dermal and pulmonary
fibroblast cultures were initiated by enzymatic techniques from
appropriate tissue taken of each group Wistar rats. Morphological
monitoring was done by phase contast microscopy; biochemical and
molecular changes of cultures obtained from animals treated
speleothropic compared to control, was experimental establised by
electrophoresis and Western Blotting techniques.
Results: Experimental data revealed the expression of several
proteins after the speleotherapeutic treatment. These data were
analysed compared with control, using a specific software.
Conclusions: Speleotherapeutic treatment of Wistar rats caused
significant differences in morphology and protein expression of
dermal and pulmonary fibroblatst grown in the laboratory. These
differences support the protective effects of speleotherapy compared
with data obtained from animals untreated and sensitized with
ovalbumin, having induced experimental asthma status.
38th World Congress of ISMH, the International Scientific Meeting of Medical Hydrology Balneology and Climatology, Lanjarón-Granada Spain, 20-23 June 2012
Health effects attributed to endocrine disrupting compounds from mud and lake waters sources
Constantin Munteanu1,2, Delia Cinteza1,2, Diana Munteanu1,2, Mihai Hoteteu1, Horia Lã
Lãzãrescu1, Daniela Poenaru1,2
E-mail:
E-mail: [email protected]
INTRODUCTION
Endocrine disruptors are substances that "interfere with the synthesis, secretion,
transport, binding, action, or elimination of natural hormones in the body that are
responsible for development, behavior, fertility, and maintenance of homeostasis
(normal cell metabolism)." They are sometimes also referred to as hormonally active
agents, endocrine disrupting chemicals, or endocrine disrupting compounds (EDCs).
EDC studies have shown that endocrine disruptors can cause adverse biological
effects in animals, and low-level exposures also cause similar effects in human beings.
The term endocrine disruptor is often used as synonym for xenohormone although the
later can mean any naturally occurring or artificially produced compound showing
hormone-like properties (usually binding to certain hormonal receptors). The term
endocrine disruptor was coined at the Wingspread Conference Centre in Wisconsin, in
1991. One of the early papers on the phenomenon was by Theo Colborn in 1993.
1
National Institute of Rehabilitation, Physical Medicine and Balneoclimatology,
Balneoclimatology, Bucharest, Romania
2
Romanian Association of Balneology ( www.bioclima.ro )
Clinical data suggest that peloidotherapy is useful in preparing the uterus for in vitro fertilization, but without scientific evidence. Mud and water from Bear Lake must be analyzed, both
in terms of physico-chemical, microbiological and in terms of phyto-and zooplankton to detect organisms that grow in the lake and are structural and biological determinants of sludge role in
studies on infertility. Previous studies conducted at the Institute of Balneology, Bucharest, have suggested the existence in the lake water of certain substances having similar effects on the
endometrium as the female sexual hormones.
Salt water and mud from lake Ursu heliothermal contain hormones released by Artemia salina: human estrogen-like SU 95%, respectively human progesterone-like 0.7 to 0.8 mg%
(Stoicescu Munteanu, 1977). They are used to treat gynecological diseases: ovarian failure, infertility, etc.
Action: Infertility (sterility) is a health problem affecting 15% of couples of reproductive age. Today only a few are known about causes and treatment options involved in the pathology
of infertility, while a number of issues remain unknown. Sapropelic mud and salt water have a high content of salt and human-like estrogen and progesterone hormones (liberated by Artemia
salina arthropode). High temperature of mud and salt water increases local circulation, implicitly the absorbtion of salt and hormones. Salt decreases local inflammation, heals genital lesions
and dissolves adherences. Hormones, with almost the same chemical structure as the human ones, are received by ovaria, hipophysis and hypothalamus as own, effectively stimulating and
balancing the own hormonal sinthesis. Ovarian synthesis of estrogen and progesterone increases, regulating menstruations, optimising vaginal pH and ovulation and prepare uterus for egg
implantation.
MATERIALS AND METHODS
Primary cultures of neonatal rat cardiomyocytes were prepared as previously described (12). Briefly, 1- to 2-day old Wistar rats were euthanized, hearts excised and ventricles minced in
phosphate- buffered saline solution. Serial digestions with 0.125% trypsin were performed at 370C; cell pellets were resuspended in Dulbecco’s Modified Eagle’s Medium Nutrient Mixture F-12
HAM (DMEM-F12) with 10% fetal calf serum, 100 UI/ml penicillin, 100 µg/ml streptomycin.
Estradiol Treatment - The 3 days cells cultures were treated with 125 pg/ml 17β-estradiol for 48h. H2O2 Treatment - Cells were treated with 10, 25 and 50 µM H2O2 by replacing the culture
medium with serum-free medium containing H2O2.
Structural Changes Following H2O2 Treatment
Immunohistochemical staining was performed using mouse monoclonal anti α-sarcomeric actin and monoclonal anti-sarcomeric tropomyosin antibodies. Cardiomyocytes contraction rate The mean contraction rate of 10 myocytes / culture well was determined microscopically.
The Endocrine Society released a scientific statement outlining mechanisms and
effects of endocrine disruptors on “male and female reproduction, breast development
and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and
cardiovascular endocrinology,” and showing how experimental and epidemiological
studies converge with human clinical observations “to implicate EDCs as a significant
concern to public health.” The statement noted that it is difficult to show that endocrine
disruptors cause human diseases, and it recommended that the precautionary principle
should be followed.
Na+/K+-ATP-ase Activity - ATP-hydrolysis was measured at 37°C following the method of Garner (3). Na/K-ATPase –dependent ATP hydrolysis is reported as nmoles Pi released/h/mg
The coronary heart disease (CHD) produces 1/5 from all deaths. Premenopausal
protein.
women have a low incidence of coronary heart disease, which rises rapidly after the
menopause towards incidence levels observed in men (1, 7). Many studies show that
estradiol reduces ischemia / reperfusion lesions (5, 6, 8, 9, 11). The estradiol effects on
cardiovascular system are multiple and the action mechanisms are not completely
understood. The aim of the present study was to characterize the effect of 17β-estradiol on
cardiomyocytes contractile function under oxidative stress conditions.
Fig. 1 – Positive immunohistochemical
reaction for α-actin; x400.
Fig. 12 - Positive immunohistochemical reaction
Fig. 4 - Positive immunohistochemical reaction for
Fig. 8 -Positive immunohistochemical reaction for αfor α-tropomyosin after estradiol treatment; x400.
α-actin after estradiol treatment; x400.
tropomyosin; x400.
Endocrine disruptors are estrogen-like and anti-androgenic chemicals in the
environment. They mimic natural hormones, inhibit the action of hormones, or alter the
normal regulatory function of the endocrine system and have potential hazardous effects
on male reproductive axis causing infertility.
Although testicular and prostate cancers, abnormal sexual development,
undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered
pituitary and thyroid gland functions are also observed, the available data are
insufficient to deduce worldwide conclusions.
Fig. 5 - Positive immunohistochemical reaction Fig. 9 - Positive immunohistochemical reaction
Fig. 2 -Neuniformly immunostaining for α- for actin after treatment with estradiol - 10 µM for α-tropomyosin after treatment with 10 µM
actin after 10 µM H2O2; x400.
H2O2 ; x400.
H2O2 ; x400.
Fig. 13 - Positive immunohistochemical reaction
for α-tropomyosin after treatment with estradiol
- 10 µM H2O2 ; x400.
RESULTS AND DISCUSSIONS
Structural Changes Following H2O2 Treatment - The oxidative stress produces α-actin
immunohistochemical reaction alteration proportionally with the H2O2 concentration (Fig.
1-3). On 50 µM H2O2 concentration no reaction was observed. Following estradiol
treatment, α-actin was detected in all of three experiments (Fig. 4-7). α-tropomyosin was
detected in cardiomyocytes with oxidative stress at all H2O2 concentrations with an
alterated morphology (Fig. 9-11). The estradiol treatment partly counteracts the effects of
oxidative stress.
Cardiomyocytes contraction rate - The 10 µM H2O2 induces a decrease with 34% of
contraction number while at the 25 and 50 µM H2O2 no contractions were observed.
Estradiol treatment produces a decrease with 16% of contraction number and no
contractions were observed at 25 and 50 µM H2O2 .
Health effects attributed to endocrine disrupting compounds include a range of
reproductive problems (reduced fertility, male and female reproductive tract
abnormalities, and skewed male/female sex ratios, loss of fetus, menstrual problems);
changes in hormone levels; early puberty; brain and behavior problems; impaired
immune functions; and various cancers.
Fig. 10 - Positive immunohistochemical reaction for Fig. 14 -Immunohistochemical reaction for αFig. 6 -Immunohistochemical reaction for actin
Fig. 3 – Reduced immunostaining for α-actin after
after treatment with estradiol - 25 µM H2O2 ; α-tropomyosin after treatment with 25 µM H2O2 ; tropomyosin after treatment with estradiol - 25
25 µM H2O2; x400.
x400.
µM H2O2 ; x400.
x400.
Na+/K+-ATP-ase Activity - Oxidative stress induces a significant decrease of Na+/K+ATP-ase activity proportionally with H2O2 concentration. Estradiol treatment partly
protects the Na+/K+-ATP-ase activity.
CONCLUSIONS
Oxidative stress is associated with muscle protein modifications. At high doses of
H2O2, actin and tropomyosin filaments aspect is dramatically changed.
Figure 3 Artemia salina (L.)
Artemia salina (L.) is a primitive aquatic arthropod (salt lakes) of the Artemiidae family
(figure 3) with an age of about 100 million years. Linný (1758) described it as Cýncer
salinus but 61 years later, Leach (1819) transferred it to Artemia salina. It was reported for
the first time in Urmia Lake in 982 by a Iranian geographer (Asem, 2008).
Fig. 7 – Alterated distribution of α-actin after
treatment with 50 µM H2O2 and estradiol;
x400.
Fig. 11 -Alterated distribution of α-tropomyosin
after treatment with 50 µM H2O2 ; x400.
Fig. 15 -Modified distribution of α-tropomyosin
after treatment with 50 µM H2O2 ; x400.
The alteration of cardiomyocytes contractility is a complex process that involves
changes of proteins activity at multiple cellular levels. Estradiol treatment attenuates the
effects of H2O2 upon muscle proteins.
8th FENS Forum of Neuroscience,
Neuroscience, Barcelona, Spain, July 1414-18 2012
Presentation Code: 127.18 Abstract Number: 186 Poster Board Number:
Number: C117
LITHIUM – TRACE ELEMENT WITH NEUROLOGICAL EFFECTS IN AFECTIVE DISORDERS
Munteanu C.1, Munteanu D.1, Cinteza D.2
E-mail: [email protected]
1Physiology,
2
Cell Cultures, National Institute of Rehabilitation, Physical Medicine and Balneoclimatology, Romania
Research and Medical Department, National Institute of Rehabilitation, Physical Medicine and Balneoclimatology, Romania
Romanian Association of Balneology ( www.bioclima.ro )
MORPHOLOGY
CONTROL
LITIU 1mM
CONTROL
LITIU 2mM
Although the cultures were determined to be
highly pure, the astrocytes presented showed a
great variation in morphology. One reason for this
variety could be the aphysiologic conditions under
which the cells were grown. Normally, cells in the
brain grow at an oxygen concentration of about
2%. Atmospheric oxygen concentrations are
usually 20%; at high oxygen concentration, many
cells in the body have been shown to exhibit
unusual morphologies.
MARIA Water
GFAP is a very sensitive and specific marker
for rapid astrocytic response to injury and disease.
MORPHOLOGY Increase of GFAP in astrocytes occurs gradually
throughout the adult lifespan. Since GFAP
LiCl 1 mM
normally increases with age and there is a wide
variation in the collection and processing of
human brain tissue, it is difficult to demonstrate
mild gliosis by immunocytochemistry. In control
GFAP
and 1 mM LiCl glial cells cultures,
immunodetection of GFAP shows a weak reaction.
2mM LiCl determine an intensification of GFAP
expression.
The inositol polyphosphate phosphatases
GSK – 3ß
selectively remove phosphate groups from various
phosphatidylinositols, which generate second
LiCl 1 mM
messengers in response to extracellular signals.
SHIP
regulates
intracellular
calcium
concentrations and may also modulate the Rad
signalling pathway.
Our results reflect a cortical reaction for SHIP
SHIP
in the control glial cultures, but the distribution of
SHIP proteins becomes heterogenic in the case of
lithium treatment with 2mM LiCl.
Immunohistochemical detections of GSK-3β
were made by an indirect immunoperoxidase
method. GSK-3β plays a critical role in the central
nervous system by regulating various cytoskeletal
processes as well as long-term nuclear events, its
inhibition may underlie some of the long-term
therapeutic effects of mood-stabilising agents. The
results presented here suggest that at 2 mM LiCl
the inhibition of GSK-3β expression is much
accentuated and this correspond to the majority of
papers which indicate GSK-3β as main target of
Adapted after Lenox and all, 2003
lithium action.
Ligand A
Wnt
PI
inositol
CMP-PA
IP3
IMPase
-
IP
PIP2
IMPase
-
IP2
PLC
γ β
α
DM
AU
GN
PI-3K
Frizzled
+
C
APC
MATERIALS AND METHODS
The primary glial cells cultures
were initiated from the brain of
Wistar rat pups aged 1-3 days, in
keeping with known techniques.
After the meninx is removed, the
brain is passed through a 60µm
nytex and the cells thus obtained
are directly plated on glass Petri
dishes with a 60 mm diameter.
The cells have been grown in a
DMEM medium (Sigma), with
4500 mg/l of glucose, 25 mM
HEPES, 100-u/ml penicillin and
100 µg/ml streptomycin (Sigma).
The medium was supplemented
with 15% calf fetal serum (Gibco).
The medium was first replaced
after 24 hrs and then every three
days. The primary cells cultures
will be maintained in a humidified
atmosphere, at 370C, with 5%
CO2.
The initial primary cultures most likely
contained neurons, astrocytes, oligodendrocytes,
other glial cells, endothelial cells and
undifferentiated cells. The shaking method of
separating cells allowed for the selection of
astrocytes, which are more readily adherent.
+ +
Ca2+
+
AXIN
INTRODUCTION
Many authors proposed that
lithium is a good treatment for
migraine and bipolar disorders.
We intend to use lithium mineral
waters,
defined
as
natural
therapeutic factors, with lithium at
safe concentrations, in prophylaxis
of anxiety and bipolar depression.
One important question that
arises for any psychiatrist is if the
lithium content of the mineral
water can or not has a therapeutic
or a prophylactic value. An initial
answer is that preliminary studies
on glial cell cultures showed a
significant modification in cell
biochemistry and morphology.
These modifications constitute an
argument for us to go on with
future experiments to clarify this
issue. Secondly, if we look to the
concentration values we have to
remark that one liter of water
contains 1.1 mEq of lithium.
This concentration is important
for us, in our intention to reach
progressively the therapeutic index
of the lithium ions.
+
Li
PKC
Akt/PKB
Dsh
-
PP2A
- - GSK-3β
GBP
Li
+
P
Phosphorylation, Translocation of
transcription factors
β-catenin
Lithium-Responsive
Gene Network
Regulation of PKC
responsive genes
SYNAPTIC FUNCTION
METHODS
Long-term Lithium
Effects
NEUROPLASTICITY
β-catenin
Protein degradation
β-catenin
TCF/LEF
TCF/LEF responsive
genes
NEUROPROTECTION
Prescriptia medicala
…
Medicina bazata pe dovezi
…
Opinia expertilor
…
Preferintele pacientilor
efectul asupra sanatatii
…
…
…
Conditiile de exploatare, utilizare – norme
igienico-sanitare
Personalul medical
Protocoale de aplicare – inclusiv pentru
persoanele sanatoase la care aplicatia se
face in scop profilactic
potential
…
Efect asupra sanatatii
…
Tipuri de cura
…
Tipuri de ape
…
Caracteristicile surselor
tipuri de cura balneara
Asistenţa medicala cu durată stabilită prin norme,
realizată printr-un program terapeutic adecvat.
…
…
…
cura balneară profilactică şi/sau de recuperare a forţei de
muncă, inclusiv cura antistress, de reconfortare,
antisurmenaj etc
cura balneară terapeutică
cura balneară de recuperare medicală pe grupe de
afecţiuni (la bolnavi cu diferite deficite funcţionale şi/sau
diferite grade de invaliditate).
potential
…
Efect asupra sanatatii
…
Tipuri de cura
…
Tipuri de ape
…
Caracteristicile surselor
tipuri de ape
…
…
principala clasificare este legata de
compozitia lor chimica
Apele minerale terapeutice reprezinta unul
din principalii factori naturali de cura,
Romania posedand circa 1/3 din rezerva
europeana
Categorii de ape minerale terapeutice si
similitudini cu zone de aparitie din Europa
Ape
carbogazoase
Covasna,Vatra Dornei,
Buzias, Tusnad, Malnas,
Balvanios etc.
Bad Meinberg, Bad Bruckenau, Bad
Hamburg (Germania), LazneTeplice,
Marianske Lazne (Cehia), Montecatini
Pelegrina, Chianciano (Italia), Vols-les
Bains, Royat (Franta), Borjomi (Rusia) etc.
Ape clorurate
sodice
Ocna Sibiului,
Someseni, Slanic
Moldova, Baltatesti,
Slanic Prahova,Sovata
etc
Salin de Jura, Balarue salins de Biarn
(Franta), Salsomagiore, Montecatini (Italia),
Droitwich, Bridge of Allan (Anglia), Ischl,
Reichenhale (Austria), Kissingen,
Hamburg, Baden Baden (Germania) etc.
Ape sulfatate
Pentru Romania nu
prezinta interes balnear;
Ivanda (Banat), Izvorul
Mircea si Breazu -Iasi
Karlovy-Vary (Cehia), Vittel (Franta), San
Pellegrino (Italia), Harrogate (Anglia),etc.
>1g/l
Ape sulfuroase
Herculane, Calimanesti,
Caciulata, Cozia, Olanesti,
Pucioasa, Mangalia,
Govora, Nicolina-Iasietc.
Ape
feruginoase
In Romania nu mai
prezinta interes terapeutic
Luchon, Larege, Cautrets, Challee
(Franta), Harragate (Anglia), Aachen
(Germania), Battaglia, Poretta (Italia),
Piestony, Teplice (Cehia) etc.
>10 mg/l
Ape arsenicale
>0,7mg/l
Ape iodurate
>1mg/l
Nu prezinta interes,conc.
admisa este <0,2mg/l
Bazna, Govora, Baltatesti,
Sarata Monteoru,
Olanesti, Calimanesti,
Caciulata etc.
Bad Tolz, Bad Wiessee (Germania),
Busko (Polonia), Solice (Italia)Lazne
Luhacovice (Slovacia) etc.
potential
…
Efect asupra sanatatii
…
Tipuri de cura
…
Tipuri de ape
…
Caracteristicile surselor
caracteristicile surselor
…
…
…
…
…
…
Perimetrul de protectie sanitara
Norme de exploatare a surselor
Legi interne care reglementeaza utilizarea
Legi care reglementeaza functionarea unei
statiuni balneare
Norme europene versus norme interne
Masuri: concesionarul, administratia locala,
autoritati sanitare si de mediu, utilizatorul
SURSE
FACTORI
POTENTIALUL BALNEAR
PROFILACTIC CURATIV SI DE
RECUPERARE
RESURSE
FINANCIARE
LEGISLATIE
NORME
RESURSE
UMANE
FACTORI
ADMINISTRATIVI
ECHIPA
DECIZIONALA
SI DE ACTIUNE
CRESTEREA CALITATII
VIETII
PROFIT
VALORIFICARE
BRAND ROMANIA
SATISFACTIA
CLIENTULUI /
PACIENTULUI
Factori ce influenteaza
valorificarea pe termen lung
CALITATEA
…
…
…
…
Prezervarea surselor de factori
Respectarea standardelor de calitate pentru
toate componentele turismului balnear
Profesionalism in toate activitatile legate de
sanatate
Personalitati medicale
Calitatea serviciilor de sanatate in
statiunea balneara
…
Actul medical balnear propriu-zis
…
Factorul terapeutic natural
…
Personalul medical
…
Echipamente medicale
…
Infrastructura
Calitatea serviciilor de sanatate
in statiunea balneara
…
…
…
…
…
…
Factori externi sau asociati
Dieta pacienti/clienti
Conditiile hoteliere si de agrement
Relatiile cu personalul
Informarea – promovarea
SERVICII MEDICALE DE URGENTA
Obtinerea si imbunatatirea
calitatii
CUM?
…
…
STANDARDIZARE - definirea unor niveluri
de performanta observabile, realizabile,
masurabile, agreate de profesionisti si
corespunzatoare populatiei/domeniului
caruia i se adreseaza
Standardele exprima asteptarile
Perspective
…
…
…
…
…
ECHIPA – coeziune, dialog, obiective
Elaborarea unei strategii de cercetare
ştiinţifică a curei balneare
Realizarea unei platforme de parteneri între
clinici şi centre medicale din staţiuni; grupuri
de lucru pe secţiuni
Cadru legislativ; co-interesare parteneri nemedicali
Parteneri internaţionali
NATIONAL INSTITUTE OF RHEABILITATION, PHYSICAL MEDICINE AND BALNEOCLIMATOLOGY
Thank you!
Dr. Biol. Constantin Munteanu
www.bioclima.ro
Email: [email protected]