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Comparative Study 2009; 30(1): 139-143 PubMed PMID: 19300396 Citation  Keywords:  Animals, Binding, Competitive, Carps:metabolism, Female, Gonadotropin-Releasing Hormone:metabolism, Humans, Mammals:metabolism, Pituitary Gland:metabolism, Protein Binding, Radioactive Tracers, Rats, Receptors, LHRH:metabolism, Salmon:metabolism,.   

OBJECTIVES: Receptor binding of GnRH is connected with the stimulation of pituitary gonadotropic cells leading to both the release and biosynthesis of gonadotropins. The binding is connected with the conformational changes in the receptor which induce the specific intracellular signalisation. The study of fish GnRHs and their receptors may give us new knowledge of the complex interplay of different mechanisms involved in neuroendocrine regulation of reproduction.

METHODS: Receptor binding of both mGnRH and sGnRH were compared by the study utilizing the displacement method with mGnRH or sGnRH as radioactive tracers. Incubation was performed at 2 degrees C to avoid ligand degradation.

RESULTS: The comparative binding of mGnRH and sGnRH with GnRH receptors from the female rat pituitary and female carp pituitary was studied. At the 50% of displacement, the binding of sGnRH to the rat pituitary receptor was very small and in comparison to the binding of mGnRH (100%) was in the range 2-15%. However, the binding of mGnRH to carp pituitary receptors is small in comparison with the binding of sGnRH (100%) and was in the range 5-20%.

CONCLUSION: The results demonstrated the differences in binding of different GnRHs to the receptor in rats and carp. This suggests that the structures of GnRH and its receptor undergo co-evolution in different classes of animals....

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Journal Article 2009; 30(1): 107-110 PubMed PMID: 19300395 Citation  Keywords:  Acromegaly:etiology, Adenoma:complications, Adrenocorticotropic Hormone:secretion, Adult, Aged, Cell Proliferation:drug effects, Cell Survival:drug effects, Drug Evaluation, Preclinical, Female, Human Growth Hormone:secretion, Humans, Hypoglycemic Agents:.   

OBJECTIVES: Rosiglitazone (RGZ) belongs to thiazolidinediones - new class of antidiabetic drugs which are PPARgamma agonists. It was shown that tumoral tissue, including the pituitary adenomas, posses PPARgamma receptors. The activation of PPARgamma receptors inhibits tumour growth in rodents and induces the oncostatic effect on human cancer cell lines. The aim of the present study was to examine the anti-tumour effect of RGZ on human pituitary adenomas in vitro.

MATERIALS AND METHODS: Cells of eight pituitary adenomas removed neurosurgically were used to our experiment. Before the operation, the hormonal secretion of the tumour was estimated. After the surgery, the histological diagnosis and immunohistochemical detection of pituitary hormones and PPARgamma receptors were performed. The cells of pituitary tumours were exposed in the primary culture to RGZ at the concentrations of 10(-9)-10(-4) M for 24 hours. To measure the cell growth the modified colorimetric Mossman method detecting the cells viability was applied.

RESULTS: On the basis of the pre-operative diagnosis the 6 clinically non-functioning adenomas (CNFPA), one case of acromegaly and one case of Cushing's disease were recognized. In 5 out of 6 CNFPA the immunopositive reaction for different pituitary hormones such as: LH, HGH, PRL, FSH and alpha-subunit was detected. Expression of PPARgamma was found in all examined tumours. Rosiglitazone decreased the cell viability of all CNFPA and corticotropinoma for 20% or more. In somatotropinoma inhibition of the cell growth was about 13%. There is no correlation between PPARgamma expression and efficacy of rosiglitazone. THE MAIN FINDING: The obtained results indicate that RZG exerts a suppressive effect on the cell viability in non-functioning pituitary adenomas. The lack of correlation between PPARgamma expression and anti-tumoral effect of RZG suggests that the above-mentioned action of this compound is independent on PPARgamma expression.

CONCLUSION: Our data suggest that rosiglitazone may be useful in the treatment of non-functioning pituitary adenomas, but its efficacy in Cushing's disease and acromegaly requires further study....

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Clinical Trial 2009; 30(1): 74-78 PubMed PMID: 19300394 Citation  Keywords:  Administration, Oral, Adult, Biological Availability, Calibration, Chemistry, Pharmaceutical:standards, Cross-Over Studies, Dose-Response Relationship, Drug, Humans, Hypoglycemic Agents:administration & dosage, Injections, Subcutaneous, Insulin:administra.   

OBJECTIVE: The purpose of this study is to investigate oral absorption of 1, 2 and 3 U/kg oral insulin five test products with different particle sizes in comparison with 0.1 U/kg subcutaneous reference formulation.

METHODS: Twenty five healthy volunteers participated in five studies using a two-phase, two-sequence crossover design with washout period of one day. Mean disposition kinetics was determined by non-compartmental analysis using Kinetica program. Absorption kinetics of insulin products were then determined using SIMCYP simulator utilizing ADAM model.

RESULTS & CONCLUSIONS: Dimensional analysis results showed the superiority of formula 4:2 U/kg oral dose with 57 nm particle size over other oral formulations when compared with subcutaneous route. Optimized intestinal permeability coefficients (x10(-4)) of insulin best test and reference formulations were 0.084 and 0.179 cm/sec respectively. Total fraction of insulin dose absorbed (Fa) for the test and reference products were 3.0% and 19% respectively. Subcutaneous product exhibited higher absorption rate and extent than oral insulin. Yet that was compensated by the increase in other factors such as Fa*, Peff* and oral dose, leading to similar insulin plasma levels and similar effect on glucose infusion rates. Oral insulin bioavailability was shown promising for the development of oral insulin product....

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Journal Article 2009; 30(1): 131-138 PubMed PMID: 19300393 Citation  Keywords:  Adult, Blood Cells:drug effects, Catechin:pharmacology, Cell Culture Techniques, Cell Nucleus:drug effects, Cell Proliferation:drug effects, Cells, Cultured, Drug Evaluation, Preclinical, Female, Humans, Interleukin-10:blood, Interleukin-6:blood, Interleu.   

OBJECTIVES: Cytokines induce the balance between inflammatory versus regulatory or antibody mediated reactions. So modulating the release of cytokines or inducing them by immunomodulating agents is an attractive mode for treating or help in treating several diseases such as autoimmune diseases. Eriobotrya japonica is a plant that is traditionally thought to have anti-inflammatory activities. Several compounds were isolated from the plant and showed distinctive biological effects. The purpose of this study was to determine the effects of epicatechin (EC) isolated from Eriobotrya Japonica on IL-6, IL-8, and IL-10 productions in whole blood stimulated with phytohemagglutinin (PHA)+lipopolysaccharide (LPS), and to examine if these cytokines are modulated through NFkappaB pathway.

METHODS: Sixteen healthy males and females volunteered in the study. Blood samples were drawn, diluted, and cultured for 24 h with different concentrations of EC and then PHA+LPS was added for another 24 h. The supernatant, then, was harvested and assayed for cytokines. In addition, mixing studies of EC and hydrocortisone were performed to examine the cytoplasmic and nuclear fractions of NFkB levels in association with cytokine production levels.

RESULTS: Increasing concentrations of EC (1-100 microg/ml) in PHA+LPS stimulated whole blood cells culture suppressed significantly (p<0.001) the production of IL-6 and IL-8. Moreover, increasing concentrations of EC modulated significantly the production of IL-10, as there was a significant increase in IL-10 level at 0.1, 1.0, and 10 microg/ml (p=0.058-0.004), while a significant decrease at a concentration of 100 microg/ml EC (p=0.037) was observed. In addition, an additive effect between EC and hydrocortisone (HC, 100 nmol/l) was seen in the production of IL-10, as there was a significant increase in IL-10 level (32%) compared with 27% for EC (10 microg/ml) and 19% HC. Furthermore, a significant decrease in cytoplasmic fractions of NFkappaB p65 level was found in samples containing EC 1, 10 microg/ml, but not in 100 microg/ml, when compared with control (p<0.03). These latter changes were accompanied with a 29%, 67%, and 98% increase, respectively, of NFkappaB p65 in nuclear fractions compared to 24% reduction of NFkappaB p65 level in HC culture (p<0.03).

CONCLUSIONS: These results indicate that EC suppresses the production of pro-inflammatory cytokines, IL6 and IL-8, enhances the production of anti-inflammatory cytokine, IL-10, and stimulates NFkappaB p65 translocation to nucleus in PHA+LPS stimulated whole blood culture....

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Journal Article 2009; 30(1): 56-60 PubMed PMID: 19300392 Citation  Keywords:  Adult, Body Mass Index, Case-Control Studies, China, Cholesterol Side-Chain Cleavage Enzyme:genetics, Female, Gene Frequency, Genetic Linkage, Genetic Predisposition to Disease, Genotype, Humans, Microsatellite Repeats:genetics, Polycystic Ovary Syndrome:.   

: Evidence indicates that CYP11alpha is a positional and functional candidate for genetic study in polycystic ovarian syndrome (PCOS). In the present study, we have evaluated the association between the CYP11alpha promoter pentannucleotide (tttta)n polymorphism and PCOS among Han Chinese women. Subjects include 125 patients with PCOS and 121 healthy controls, and all were Han Chinese women. Clinical characteristics of patients with PCOS and control subjects were examined according to the Rotterdam consensus criteria. The CYP11alpha promoter pentannucleotide (tttta)n polymorphism was genotyped with PCR and fluorescent capillary electrophoresis protocol. Results indicate that common alleles of the CYP11alpha promoter pentannucleotide (tttta)n polymorphism in this population of Han Chinese women were P4, P6 and P8, and allele P6 was the most common one. Frequencies of those three common alleles between PCOS cases and controls (24.8, 65.6, 6.8% and 23.6, 65.7, 9.9%, respectively) were similar. No significant allelic association of this polymorphism with PCOS was found. However, the carriers with allele P6 among patients with PCOS had increased WHR (0.85+/-0.05 vs 0.82+/-0.08, P=0.039) and decreased AUCG (9.5+/-2.1 vs 11.4+/-2.8, P=0.021) compared to the patients carrying other alleles. Therefore, the most common allele of the CYP11alpha promoter pentannucleotide (tttta)n polymorphism in the population of Han Chinese women is P6, while the most common allele in European Caucasians, as previously reported, is P4. This polymorphism is an ethnic and racial variant, and may have the risk susceptibility in abnormal metabolism of patients with PCOS in Han Chinese women....

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Comparative Study 2009; 30(1): 111-118 PubMed PMID: 19300391 Citation  Keywords:  Abortion, Induced:statistics & numerical data, Adolescent, Adult, Birth Rate:trends, Czech Republic:epidemiology, Europe:epidemiology, Female, Humans, Middle Aged, Population Growth, Pregnancy, Reproduction:physiology, Young Adult,.   

OBJECTIVES: The aim of study was to evaluate the importance of induced abortions for reproduction medicine in Czech Republic.

DESIGN: Demographic analysis of data published by EUROSTAT and Czech statistical office.

SETTING: Department of Demography and Geodemography Faculty of Science, Charles University Prague.

RESULTS: Widespread use of the liberal abortion law in socialist countries contributed to the decline of fertility rates only to the replacement level. In the Czech Republic total fertility rate dropped below 1.3 in 1995 and it did not increase above 1.5 children per woman till 2007. The increased use of modern contraceptive methods that results in a sharp decline in fertility and in a significant decrease of induced abortions can be documented. The total abortion rate fell from 1.54 abortions per a woman in 1990 to 0.34 in 2007. The proportion of women aged 15-49 years who were prescribed oral contraception increased from 4 percent in 1990 to 48 percent in 2007. An induced abortion is still used largely as a way to avoid birth of additional children by women who already have the number of children they want. This is in sharp contrast with the situation in the majority of Western European countries in which abortion is used mainly by teen-age girls whose attempts to avoid pregnancy have failed.

CONCLUSION: In contrast to other demographic characteristics which classify the Czech Republic to Eastern Europe, the level of induced abortion rate is comparable with the levels observed in some Western European countries....

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Journal Article 2009; 30(1): 119-124 PubMed PMID: 19300390 Citation  Keywords:  Adult, Brain Mapping, Case-Control Studies, Cerebrum:pathology, Depression:complications, Diabetes Mellitus:pathology, Diabetic Neuropathies:complications, Dominance, Cerebral:physiology, Evoked Potentials, Visual, Female, Humans, Male, Middle Aged, Psych.   

OBJECTIVES: The present study was undertaken in order to verify the hypothesis stating that patients with depression exhibit some abnormalities concerning a cerebral symmetry. For this purpose, an analysis of the relationship between the VEPs (Visual Evoked Potentials) results and the depressive symptoms intensification, as well interrelation between depressive and diabetic symptoms were performed.

MATERIAL AND METHODS: VEPs recordings were obtained from the two study groups (both aged 20-45 years), 20 healthy subjects and 32 diabetic patients with clinically documented depression. The VEPs examination was carried out using a computer system called STELLA (Stimulated Electroencephalogram on Line Analyzer).

RESULTS: VEPs examinations revealed a cerebral symmetry in the all control subjects and in 10 out of 32 diabetic patients with depressive disorders. It is noteworthy that 22 of 32 diabetic patients (68.8%) showed a hemispheric asymmetry in the VEPs recordings. Of 12 patients with a moderate depression, 10 showed the left cerebral laterality, and 2--the right laterality. In turn, all 10 patients with major depressive disorder (MDD) demonstrated in the VEPs recordings a significant cerebral laterality with the right hemisphere dominance.

CONCLUSIONS: The obtained results suggest that interhemispheric cerebral asymmetry might be considered a specific feature of depression, and, if this is a case, it could justify a conclusion that right hemisphere dominance could be a neurophysiological marker of MDD. It should be emphasized that intensification of the depressive symptoms has an unfavorable influence on course of diabetes mellitus, its self-control and severity of following complications....

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Evaluation Studies 2009; 30(1): 11-16 PubMed PMID: 19300389 Citation  Keywords:  Antidepressive Agents:pharmacology, Humans, Hypothalamo-Hypophyseal System:drug effects, Mood Disorders:drug therapy, Pituitary-Adrenal System:drug effects, Receptors, Glucocorticoid:physiology, Transcription, Genetic:physiology,.   

: Changes in the hypothalamic-pituitary-adrenal (HPA) axis are characteristic of major depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GR's in depressed patients. Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of corticotropin-releasing hormone (CRH) in various brain regions postulated to be involved in the causality of major depression. Hyperactivity of HPA axis is the main biochemical change, besides disturbed monoaminergic neurotransmission, observed in the patients suffering from a major depression. High incidence of depression in Cushing's syndrome as well as antidepressant effects of adrenocortical enzyme inhibitors in major depression support hypothesis that hyperactivity of HPA axis may be involved in pathogenesis of depression. Major alterations of the HPA axis that can be reversed by successful antidepressant therapy are often seen in depressed patients. A possible explanation for this is that the antidepressant-induced increase in GR's renders the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of antidepressant drugs....

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