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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.r />r /> 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.r />r /> 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.r />r /> 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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Comparative Study 2006; 27(5): 639-643 PubMed PMID: 17159821 Citation  Keywords:  Acromegaly:blood, Adenoma:complications, Adult, Aged, Colonic Polyps:complications, Colonoscopy:methods, Colorectal Neoplasms:complications, Female, Fluorescence, Growth Hormone:blood, Humans, Insulin-Like Growth Factor I:analysis, Male, Middle Aged, Pitu.   

OBJECTIVES: Acromegalics have an increased risk of colorectal neoplasm. The aim of this study was to establish the association between acromegaly and colorectal lesions.r />r /> MATERIALS AND METHODS: The study included 51 patients with active acromegaly: 30 women and 21 men (average age 52.95 +/- 13.49 years). Growth hormone (GH), insulin-like growth factor I (IGF-I), prolactin (PRL), thyreothropin (TSH), thyroxine (FT4) were measured in the serum when patients were hospitalized for their first diagnosis of acromegaly, before starting the treatment. All patients underwent colonoscopy--in the first phase conventional in white light; in the second phase fluorescence colonoscopy. Autofluorescence of colonic mucosa was assessed by illumination with monochromatic light. Green fluorescence is characteristic for normal colonic mucose, whereas red fluorescence occur in pathological lesions. Material to histopathological examination was taken from every pathological colorectal lesion.r />r /> RESULTS: Using conventional colonoscopy we detected colonic polyps in 21 acromegalic patients (41.17%). Polyps with red fluorescence were found in 7 (13.7%) acromegalics and with green fluorescence in 16 (31.37%) cases of these patients. Histological diagnoses of colorectal lesions are adenoma, hyperplastic and inflammatic polyps. The number of colorectal polyps was dependent on IGF-I, fT4 and sex.r />r /> CONCLUSIONS: Acromegaly is associated with high prevalence of colorectal pathology, mainly hyperplastic polyp and adenoma. There is a relationship between number of colorectal polyps and serum IGF-I levels in acromegaly. Adenomas and hyperplastic polyps were associated with higher levels of IGF-I....

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Comparative Study 2006; 27(5): 623-630 PubMed PMID: 17159820 Citation  Keywords:  Adenine Nucleotides:analysis, Adenosine Triphosphatases:metabolism, Adenosine Triphosphate:biosynthesis, Animals, Diaphragm:drug effects, Melatonin:pharmacology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Muscle:chemistry, Muscle, Skeletal:ch.   

OBJECTIVES: To evaluate the changes in the mitochondrial ATP production during sepsis and the participation of iNOS in these changes. We also assessed the effect of melatonin administration in this experimental paradigm.r />r /> METHODS: The activity of ATPase, the level of adenine nucleotides, and the ATP production were measured in mitochondria of diaphragm and hind leg skeletal muscle of wild type (iNOS+/+) and knockout iNOS (iNOS-/-) mice. Three experimental groups were done: control group; group of septic mice induced by cecal ligation and puncture (CLP), and group of septic mice treated with melatonin. Mice were killed 24 hours after CLP. Melatonin was administrated in four doses (30 mg/kg b.w.) as follows: 30 min before CLP (i.p.) and 30 min, 4 h and 8 h after CLP (s.c.).r />r /> RESULTS: Mitochondrial production of ATP decreased in iNOS+/+ but not in iNOS-/- mice after sepsis. No changes in the ATPase activity were found in any group. Melatonin treatment normalized the production of ATP in iNOS+/+ mice, without affecting iNOS-/- animals.r />r /> CONCLUSIONS: The reduction of the ATP production in iNOS+/+ but not in iNOS-/- mice suggest the participation of iNOS in the impairment of mitochondrial function in the former. Because ATPase was unaffected by sepsis, it is suggested the ATP deficit depended on the sepsis-induced respiratory chain damage. The normalization of the production of ATP with melatonin may explain the reduction of the mortality reported elsewhere in experimental and clinical sepsis after treatment with the indoleamine....

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Clinical Trial 2006; 27(5): 659-664 PubMed PMID: 17159819 Citation  Keywords:  Estradiol:administration & dosage, Female, Follicle Stimulating Hormone:blood, Humans, Hydrocortisone:blood, Luteinizing Hormone:blood, Melatonin:blood, Middle Aged, Postmenopause:blood, Time Factors,.   

OBJECTIVES: It has been well-documented that serum melatonin levels are insensitive to estrous or menstrual ovarian steroid variations in the female rat or the human. However, a negative coupling has been already demonstrated between the nocturnal serum melatonin peak and serum E2 concentration during the late premenopausal period in the woman. The objection of the present study was designed to determine if diurnal serum melatonin values can be also lowered by a single administration of estrogen.r />r /> METHODS: We performed a detailed analysis of variations of serum estradiol, LH, FSH, melatonin and cortisol after one single I.M. injection of 2 mg of a conjugated estrogen, delestrogen (estradiol valerate) in 0.1 ml of oil. A 15 ml blood collection was done at 8:00 a.m. before the injection, and at 8:30 a.m., 9:00 a.m., 10:00 a.m., 12:00 noon, and 4:00 p.m. 17beta-estradiol, LH and FSH were determined by microparticle enzyme immunoassays kits. Melatonin determination was made using a RIA kit and cortisol was assayed by a RIA method.r />r /> RESULTS: A significant rise in serum 17beta-estradiol was already seen by one hour after the injection of estradiol valerate. Then, an almost linear increase was observed up to at last eight hours after the injection of estradiol valerate. A significant decrease in serum LH was not seen before four hours after the injection of estradiol valerate. Overall, there was a trend toward a decline in serum melatonin and cortisol concentration. The decreasing trend of cortisol serum level was tested as significant over time (p< 0.001). However, the decrease in serum concentration did not reach a significant level for melatonin.r />r /> CONCLUSION: Overall, these results show that after menopause an acute administration of estrogen during the early diurnal period of the day leads to a significant rapid decrease in cortisol serum values, but to only a partial non significant decrease in melatonin serum values....

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Controlled Clinical Trial 2006; 27(5): 587-594 PubMed PMID: 17159818 Citation  Keywords:  Adolescent, Adult, Basal Metabolism, Brain:metabolism, Brain Mapping, Female, Fluorodeoxyglucose F18:metabolism, Frontal Lobe:metabolism, Humans, Male, Middle Aged, Positron-Emission Tomography:methods, Psychomotor Performance, Schizophrenia:metabolism, T.   

OBJECTIVES: With the aim to indicate the functional anatomical substrate of cognitive dysfunction in schizophrenia we evaluated the relationship between resting brain metabolism and performance on the Trail Making Test (TMT). As the prerequisite analysis we compared the performance in Part A and B of the TMT between schizophrenic patients and controls. Resting brain metabolism was investigated by (18)FDG positron emission tomography (PET) as the probe for the relative regional synaptic strength and density.r />r /> METHODS: (18)FDG PET data were analyzed by SPM99 with TMT A and B as the covariate (p< or =0.001).r />r /> RESULTS: Schizophrenic patients (N=42) had worse performance in both TMT A and B compared to controls (N=42). In schizophrenic subjects (18)FDG PET did not predict the performance on Part A (psychomotor speed) but predicted that for Part B (set-shifting and flexibility) of the TMT. The (18)FDG uptake in the superior, middle and inferior frontal gyruses bilaterally was associated with better performance in the TMT B. The negative covariation between 18FDG uptake and time spent in the TMT B was detected in the temporal and parietal cortices, pre- and postcentral gyruses, precuneus limbic regions (anterior cingulate, uncus) and the pons.r />r /> CONCLUSIONS: Our data indicate that hypometabolism in the frontal lobes and hypermetabolism in the temporo-parieto-limbic regions is the neurobiological basis for deficient TMT B performance in schizophrenia....

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Comparative Study 2006; 27(5): 615-621 PubMed PMID: 17159817 Citation  Keywords:  Adult, Epitopes:immunology, Fatigue Syndrome, Chronic:blood, Fatty Acids:immunology, Female, Humans, Immunoglobulin M:blood, Male, Middle Aged, Oxidative Stress:immunology, Proteins:immunology, Reactive Nitrogen Species:immunology, Reactive Oxygen Species.   

: There is now some evidence that chronic fatigue syndrome (CFS) is accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS is accompanied by an immune response to neoepitopes of a variety of modified lipids and proteins indicating damage caused by oxidative and nitrosative stress. Toward this end we examined serum antibodies to fatty acids (oleic, palmitic and myristic acid), by-products of lipid peroxidation, i.e. azelaic acid and malondialdehyde (MDA), acetylcholine, S-farnesyl-L-cysteine, and N-oxide modified amino-acids in 14 patients with CFS, 14 subjects with partial CFS and 11 normal controls. We found that the prevalences and mean values for the serum IgM levels directed against oleic, palmitic and myristic acid, MDA, azelaic acid, S-farnesyl-L-cysteine, and the N-oxide derivates, nitro-tyrosine, nitro-phenylalanine, nitro-arginine, nitro-tryptophan, and nitro-cysteinyl were significantly greater in CFS patients than in normal controls, whereas patients with partial CFS took up an intermediate position. There were significant and positive correlations between the serum IgM levels directed against fatty acids, MDA and azelaic acid and the above N-oxide-derivates and the severity of illness (as measured by the FibroFatigue scale) and symptoms, such as aches and pain, muscular tension and fatigue. The results show that CFS is characterized by an IgM-related immune response directed against disrupted lipid membrane components, by-products of lipid peroxidation, S-farnesyl-L-cysteine, and NO-modified amino-acids, which are normally not detected by the immune system but due to oxidative and nitrosative damage have become immunogenic....

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Comparative Study 2006; 27(5): 595-599 PubMed PMID: 17159816 Citation  Keywords:  Animals, Antioxidants:pharmacology, Antithyroid Agents:pharmacology, Diet, Dose-Response Relationship, Drug, Kidney:chemistry, Liver:chemistry, Lung:chemistry, Male, Oxidative Stress:drug effects, Potassium Iodide:administration & dosage, Propylthiouracil.   

OBJECTIVES: Iodide administration to animals, living in iodine-deficient areas, can induce oxidative processes in the thyroid gland and increase concentration of lipid peroxidation (LPO). Propylthiouracil (PTU)--a well-known antithyroid drug--may also act as an antioxidant. There are some reports, which consider the protective ability of this drug against LPO. The goal of the study was to evaluate oxidative processes and the protective role of PTU in three rat organs during treatment with pharmacological doses of iodide.r />r /> MATERIAL AND METHODS: Schiff's bases (SB) concentrations (a parameter of oxidative stress) were measured in liver, lung and kidney homogenates of male Wistar rats. For 2 weeks the animals received iodides in their diet in the following concentrations: Group 1--Controls (standard diet, approx. 0.7 mg of potassium iodide per kg; KI/kg); Group 2--diet containing 0.25 mg KI/kg; Group 3--diet with 4.0 mg KI/kg; Group 4--diet with 8.0 mg KI/kg. Group 5--standard diet with 0.1% of PTU in drinking water for two weeks. Subsequent tree groups (6-8) received KI in their diet in doses as above, respectively, together with PTU.r />r /> RESULTS: We noted increased SB levels in the lungs and in the liver, compared to those observed in the control group. We also found decreased SB concentrations in liver and lung homogenates after the administration of PTU but, unexpectedly, the level of SB increased in kidney homogenates of all the groups.r />r /> CONCLUSIONS: The results of this study indicate that iodine is involved in oxidative processes in different organs and PTU protects against iodine-induced oxidative stress....

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Comparative Study 2006; 27(5): 651-657 PubMed PMID: 17159815 Citation  Keywords:  Adult, Aged, Aged, 80 and over, Alcoholic Beverages:statistics & numerical data, Alcoholism:epidemiology, Biomarkers:analysis, Comorbidity, Female, Health Status, Humans, Male, Mental Disorders:epidemiology, Middle Aged, Psychological Tests, Social Class,.   

OBJECTIVES: To test the hypothesis that early-onset alcoholism can be differentiated from alcoholism in the elderly by more severe substance related problems, more frequent family history, higher mortality rate, and antisocial behaviour.r />r /> METHODS: 73 elderly (E) alcoholics (mean age 70.2 yrs) were compared with 90 young (Y) alcoholics (mean age 43.9 yrs) and 70 elderly non alcoholics (mean age 76 yrs). We focused on, family history (FH), co morbidity, mortality, biological markers (AST, GGT, MCV), and demographics. Geriatric Scale of Depression, Standardized Mini-Mental State Examination and Munich Alkoholism Test were also used. All results analysed by the SPSS.r />r /> RESULTS: FH was significantly (p<0.001) more often positive in Y (52%) than in E (15%) and C (10%). Significantly (p<0.001) more E (57.5%) are married than Y (37.8%) and C (21.4%), significantly (p<0.001) more E (72. 6%) has elementary education compared with Y (44.4%). E alcoholics abstain significantly (p<0.001) more (>27 months) than Y ones (approximately 11 months). Significantly (p<0.001) more Y (43%) had forensic history than E (8.2%). Significantly (p<0.01) more death rate was found in E (19.2%) than in Y (5.6%) and C (1.4%). Significantly (p<0.01) more E (61%) prefer spirits than Y (21%), but significantly more Y (>63%) combine spirits with beer and wine than E (>32%). Significantly (p<0.001) more alcoholics (E and Y) had elated levels of MCV (>70%), AST and GGT (>60%) than C. We have found significantly (p<0.001) higher rate of comorbidity of CNS diseases, GIT, injuries, haematological and infectious diseases in the groups of elderly and young alcoholics than in C subjects. On the other hand, prevalence of cardiovascular, ORL, ophtalmological, endocrine and orthopedic diseases were significantly (p<0.01) higher in C. To compare elderly patients with young ones, we found significantly (p<0.01) higher rate of respiratory, endocrine, cardiovascular and CNS diseases, and dementia in E alcoholics (p<0.001). Depression and abuse of prescribed medication was significantly (p<0.01) more often in the C, but suicide attempts, neurotic spectrum disorders and personality disorders were significantly (p<0.01) often in group of Y.r />r /> CONCLUSION: Young alcoholics have significantly more often positive FH, drink significantly bigger amounts of alcohol, have more forensic history, and personality disorders in comparison to elderly ones. On the other hand elderly alcoholics tend to have more somatic complication due to alcohol abuse, but drink less alcohol, tend to abstain longer, and have less psychopathic traits. In contrast to literature, the majority of elderly alcoholics are married, have low education and do not belong to high social classes....

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