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Journal Article 2008; 29(1): 75-79 PubMed PMID: 18283248 Citation  Keywords:  Aged, Aged, 80 and over, Alzheimer Disease:blood, Amyloid beta-Peptides:blood, Biomarkers:blood, Case-Control Studies, Female, Humans, Interleukin-10:blood, Interleukin-6:blood, Middle Aged, Tumor Necrosis Factor-alpha:blood,.   

: Alzheimer's disease (AD) belongs to a group of neurodegenerative disorders. It is characterized by irreversible and progressive memory loss accompanied with decline in other cognitive functions. At a microscopic level, the typical neuropathologic features, senile plaques and neurofibrillary lesions are found. The pathological processes lead to neuronal loss, synaptic dysfunction and inappropriate activity of neurotransmitters. The major constituent of senile plaques is abnormally aggregated beta amyloid protein. Beta amyloid (Abeta) is a short (40-42 amino acid) product of proteolysis of the transmembrane amyloid precursor protein (APP). Extracellular depositions of Abeta 1-42 may initiate a wide range of pathological processes including glia activation, neuroinflammation and neuronal apoptosis. There is convincing evidence that inflammatory response to accumulation of beta amyloid plays a pivotal role in the progression of neuropathological changes found in AD. Current research was directed at assessing beta amyloid, cytokines (IL-6, IL-10 and TNF alpha) plasma levels in women with AD. Hundred and twenty four women, aged between 59 to 86 years, were enrolled in the study. Amongst them 57 were diagnosed with AD (29 subjects in early stage and 28 subjects with moderate to severe stadium of disease) and 67 women without dementia were investigated as a control group. The lowest values of Abeta 1-42 were found in AD subjects in moderate to severe stage of disease as compared with the early stage of AD (p< 0.05) and the control group (p<0.01). Change in IL-6 values was significantly different between groups with the lowest values found in women without dementia. Both subset of AD patients demonstrated statistically enhanced IL-6 levels when compared with the control group (p<0.001, p<0.01 respectively for early and moderate/severe stage of AD). Moreover, our study revealed a trend to increase in TNF alfa and IL-10 values in AD. However, those differences were not statistically significant. In addition, we did not detect any correlations between plasma beta amyloid and investigated cytokines....

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Journal Article 2007; 28(5): 671-674 PubMed PMID: 17984938 Citation  Keywords:  Animals, Aromatase:metabolism, Cholestenone 5 alpha-Reductase:metabolism, Female, Hypothalamus, Middle:embryology, Immobilization, Pregnancy, Prenatal Exposure Delayed Effects, Preoptic Area:embryology, Rats, Rats, Wistar, Sex Characteristics, Stress, Psy.   

OBJECTIVES: Prenatal stress results in demasculinization and feminization of sexual behavior in adult male rats. Earlier the preventive effect of testosterone replacement of an androgen deficiency in male fetuses during exposure to stress has been demonstrated. Nevertheless the neuroendocrine mechanisms underlying hormonal protection of the brain sexual differentiation are not clear.

MATERIAL AND METHODS: Time-mated rats were undergone to 1 h strict immobilization during days 15 to 21 of gestation. Another group of stressed dams was injected with testosterone propionate on the 17th, 19th and 21st gestational days subcutaneously (5 mg/kg b.w.) 30 min prior to restraining. Aromatase and 5alpha-reductase activities were determined in the preoptic area and medial basal hypothalamus of 10-day old offspring.

RESULTS: Aromatase activity in the preoptic area declined in affected with prenatal stress males and reached the normal female level. It completely restored in prenatally stressed males under influence of prenatal testosterone replacement. 5alpha-reductase activity decreased in the preoptic area of prenatally stressed females. In those pretreated with testosterone propionate, 5alpha-reductase activity was significantly elevated above normal level.

CONCLUSIONS: The data obtained demonstrate a preservation of aromatase activity in the preoptic area of males resulted from testosterone replacement. Presumably testosterone exerts its protective effect on the male sexual behavior by prevention of neurochemical feminization of the brain preoptic area and, perhaps, due to some other mechanisms....

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Clinical Trial 2007; 28(1): 17-20 PubMed PMID: 17277731 Citation  Keywords:  Adolescent, Adrenal Medulla:physiology, Adult, Choice Behavior:physiology, Humans, Impulsive Behavior:metabolism, Male, Saliva:chemistry, Sympathetic Nervous System:physiology, Testosterone:metabolism, alpha-Amylases:analysis,.   

OBJECTIVE: Little is known regarding the role of the sympathetic-adrenal-medullary (SAM) system in self-control and impulsivity in intertemporal choice (delay discounting), although the roles of dopaminergic and serotonergic systems have been extensively examined. This study was aimed to examine the relationships between salivary alpha-amylase (sAA, a non-invasive biological marker of adrenergic/SAM activities) levels and hyperbolic discounting, which is of interest in psychoneuroendocrinology and neuroeconomics.

METHODS: We assessed degrees to which delayed monetary gains were discounted (hyperbolic discount rates) in healthy male students. Participants' sAA were also assessed.

RESULTS: We observed negative relationships between sAA and hyperbolic discounting of small, medium, and large monetary gains.

CONCLUSIONS: The results indicate that subjects with low sAA are impulsive in intertemporal choice. Implications for the roles of adrenergic and SAM systems in self-control in intertemporal choice are discussed....

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Journal Article 2006; 27(6): 795-798 PubMed PMID: 17187004 Citation  Keywords:  Adult, Female, Glycoprotein Hormones, alpha Subunit:metabolism, Humans, Male, Middle Aged, Prolactin:metabolism, Reference Values, Stimulation, Chemical, Thyroid Function Tests, Thyrotropin:metabolism, Thyrotropin-Releasing Hormone:physiology,.   

OBJECTIVE: The alpha-subunit (Alpha-SU) response to TRH was studied to examine the response of alpha-SU under TRH stimulation in normal situation.

METHODS: Thirty seven healthy individuals were included in the study. They were divided into two groups according to the data taken: A with TSH equal or more than seven fold the basal values (0: 3.14+/-1.2 microU/ml., 30 after TRH: 20.22+/-4.6 microU/ml) and B with TSH 2 to 6 fold the basal values (0: 0.5+/-0.1 microU/ml., 30 after TRH: 2.9+/-0.5 microU/ml). Both groups exhibited similar FT3 and FT4 levels.

RESULTS: In group A, prolactin displayed a 3 fold increase from the basal values, whereas alpha-SU increased 4 fold with a difference being statistically significant (p<0.001). In contrast, in group B individuals neither prolactin nor alpha-SU exhibited any significant difference from the basal values.

CONCLUSION: The expression of alpha-SU upon TRH stimulation is dependent on the TSH basal values....

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Comparative Study 2006; 27(5): 675-678 PubMed PMID: 17159822 Citation  Keywords:  5-alpha-Dihydroprogesterone:pharmacology, Animals, Cell Line, Cell Survival:drug effects, Dose-Response Relationship, Drug, Lipopolysaccharides:pharmacology, Mice, Microglia:cytology, Nitric Oxide:secretion, Pregnanolone:pharmacology, Progesterone:metabol.   

OBJECTIVE: Microglial cells, important immunosurveillance cells in the nervous system, respond to pathogens with an increase in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release. Because excessive release of NO may be neurotoxic, tight regulation of nitrosative stress is required.

DESIGN AND SETTING: We cultured the murine microglial cell-line, BV-2, with bacterial lipopolysaccharide (LPS) to induce NO synthesis and quantified the impact of progesterone and its metabolites, 5alpha-dihydroprogesterone (DHP) and 5alpha-3alpha-tetrahydroprogesterone (THP), on NO release.

RESULTS: Our in vitro experiments showed that in BV-2 cells LPS-induced NO release is suppressed by progesterone and THP. Both neurosteroids decreased NO release by about 40% when used at a concentration of 10 microM. NO release was less sensitive to DHP. This neurosteroid decreased NO release only by 20% when used at a concentration of 10 microM. NO release was sensitive to N(G)-methyl-L-arginine (L-NMMA), a completive inhibitor of NOS, indicating that LPS-induced NO release is mediated by NOS activity. Trypan blue exclusion experiments showed that the ratio of viable to dead cells did not vary using different concentrations of progesterone. Furthermore, progesterone did not increase apoptosis or necrosis when estimated by the distribution of DAPI-labelled condensed chromatin.

CONCLUSION: These experiments indicate that the decline in NO release is mainly due to modulation of NOS activity or expression. Because progesterone, DHP, and THP are synthesized in astrocytes and oligodendrocytes, these neurosteroids may locally suppress an immune response....

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Journal Article 2006; 27(1-2): 177-182 PubMed PMID: 16670672 Citation  Keywords:  Animals, Antigens:genetics, Cell Count, Cerebral Cortex:cytology, Female, Immunohistochemistry, Leptin:pharmacology, Mice, Mice, Inbred ICR, Oligodendroglia:drug effects, Pregnancy, Proteoglycans:genetics, Receptor, Platelet-Derived Growth Factor alpha:bi.   

OBJECTIVE: Leptin, which is an obese gene product, decreases appetite and increases energy expenditure in adults. In our previous study, leptin was found to maintain neural stem cells and/or progenitor cells, preferentially astrocyte/oligodendrocyte progenitor cells, whereas it reduces the proportion of oligodendrocyte lineage-restricted precursor cells. It has been reported that leptin-deficient (ob/ob) mice have lower levels of glial proteins than wild-type mice. These findings suggest that leptin affects the development of glial cells. In this study, therefore, we investigated oligodendrocyte development in the cerebral cortex of ob/ob and wild-type mouse embryos by histochemistry.

METHODS: We obtained ob/ob or wild-type (C57BL/6J) embryos on embryonic day (E) 18. We performed immunohistochemistry in the embryonic cerebrum with antibodies against NG2, platelet-derived growth factor receptor-alpha (PDGFR-alpha) and leptin receptor (Ob-R). In the cerebral cortex, we compared the number of the oligodendrocyte precursor cells (OPCs), which are immunopositive for NG2 and/or PDGFR-alpha, between ob/ob and wild-type embryos.

RESULTS: We revealed that ob/ob embryos had significantly more OPCs than wild-type embryos on E18. PDGFR-alpha-positive OPCs did not coexpress leptin receptor in the cerebral cortex.

CONCLUSION: These findings suggest that leptin inhibits differentiation of multipotent and/or glial progenitor cells into OPCs in the mouse embryonic cerebral cortex, but it does not directly act on OPCs....

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Journal Article 2006; 27(1-2): 121-127 PubMed PMID: 16648778 Citation  Keywords:  Adrenergic alpha-Agonists:therapeutic use, Aged, Blood Pressure:drug effects, Cardiac Output:drug effects, Cardiotonic Agents:pharmacology, Critical Illness, Dobutamine:therapeutic use, Female, Heart Rate:drug effects, Humans, Hydrazones:pharmacology, Int.   

UNLABELLED: Levosimendan may improve the outcome of acute heart failure patients with preserved arterial blood pressure. However, the data on its use in critically ill patients are scarce.

OBJECTIVES: The aim of this study was to assess the effects of levosimendan on global haemodynamics in patients with cardiogenic shock.

MATERIALS AND METHODS: Fourteen adult patients in cardiogenic shock were studied prospectively. One patient died after 10 hours and was excluded from final analysis. Haemodynamic monitoring included arterial and pulmonary arterial thermodilution catheters. Before levosimendan administration, 12 patients required norepinephrine, 6 patients dobutamine and 4 patients intraaortic balloon pump. Levosimendan was given as a bolus (12 microg x kg(-1) x 10 min(-1)) followed by 24 hrs infusion (0.1 microg x kg(-1) x min(-1)). Baseline data had been collected before levosimendan administration. Following data sets were obtained after 1, 8, 16 and 24 hours. Positive haemodynamic response was defined as an increase of > or = 30% in cardiac output.

RESULTS: Eleven patients met the criterion for the positive haemodynamic response. During levosimendan infusion systemic vascular resistance decreased (p<0.05) whereas cardiac output (p<0,001) and urine output increased (p<0.01). Mean arterial pressure and heart rate remained unchanged. No severe arrhythmias occurred and norepinephrine-dose did not change. Two patients were classified as non-responders.

CONCLUSIONS: Our results suggest that levosimendan infusion given as adjunctive therapy in patients with cardiogenic shock may be safe with beneficial effects on global haemodynamics....

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Journal Article 2005; 26(6): 789-794 PubMed PMID: 16380674 Citation  Keywords:  Adult, Case-Control Studies, Female, Genetic Predisposition to Disease:epidemiology, Genetics, Population, Humans, Integrin alpha2:genetics, Integrin beta3:genetics, Labor, Obstetric:blood, Polymorphism, Genetic, Pregnancy, Pregnancy Complications, Hemato.   

OBJECTIVE: The aim of the study was to evaluate the prevalence of the GP Ia and GP IIIa polymorphisms in the group of women in labor, and to assess the risk of thrombosis associated with their occurrence.

DESIGN AND SETTINGS: 245 women in labor hospitalized between 1.01.2001 and 31.12.2003 r. were enrolled in the study. Patients were qualified for the study if detailed physical exam and past medical history excluded existence of known risk factors predisposing to thrombosis. Study group was composed of 72 women in childbirth, which at some point during current pregnancy or in early labor were diagnosed with thrombosis, and control group included 173 women in labor randomly picked from the group of patients with uncomplicated pregnancies. Polymorphic regions of platelets glycoprotein were detected using genotyping methods based on polymerase chain reactions (PCR).

RESULTS: 1.72% of patients were found to have thrombosis. The thrombosis was located in the venous system in 97.2% of cases. Arteries were affected in two patients (2.7%). Prevalence of individual platelets glycoprotein mutations did not differ between controls and study group. In both groups platelets glycoprotein polymorphisms moderately pro-thrombotic A1/A2 and C/T dominated, and the least numerous were strongly pro-thrombotic A2/A2 and T/T.

CONCLUSIONS: Our results did not show the causative relationship between the existence of platelets GP IIIa/GP Ia mutations and venous system thrombosis in the women in labor. Probably presence of pro-thrombotic mutations of platelets glycoprotein in this group of patients does not represent the increased risk of thrombosis....

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