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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.

METHODS: (18)FDG PET data were analyzed by SPM99 with TMT A and B as the covariate (p< or =0.001).

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.

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): 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.

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.

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.

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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Journal Article 2006; 27(5): 609-613 PubMed PMID: 17159813 Citation  Keywords:  Adult, Aged, Carcinoma:genetics, Cell Adhesion Molecules:genetics, DNA Methylation, Female, GPI-Linked Proteins, Gene Expression Regulation, Neoplastic, Humans, Middle Aged, Ovarian Neoplasms:genetics, Promoter Regions, Genetic, RNA, Messenger:metabolism,.   

OBJECTIVE: The expression profile of the OPMCL gene was studied to find out if there was any evidence of a CpG island methylator phenotype and if there was an association of CpG island methylation with the gene downregulation in women with ovarian cancer.

MATERIAL AND METHODS: Expression of OPCML in 43 ovarian cancer tumor samples and in 4 normal ovaries was determined by RT-PCR. Methylation status of OPCML promoter region was studied with methylation-specific PCR (MSP) method. Possible associations with selected clinicopathologic variables: FIGO stage, histological grade, patient's age and menopausal status were tested.

RESULTS: In all normal ovarian samples OPCML mRNA was present, but it was not detectable in 24 of 43 ovarian cancer cases. We have not found the relationship between age and menopausal status with the presence of RTPCR product of OPCML. Hypermethylation of OPCML was not correlated to FIGO stage, however, in 80% of cases with methylated OPCML early clinical stage was also present. Tumor grading and histological type had no significant influence on the presence of hypermethylation of OPCML gene. In 20 of 43 cases of ovarian cancer methylated product of MSP amplification was present. In a group of OPCMLmRNA-negative tumors there were 75% of cases with hypermethylated exon of OPCML and the correlation between these variables was statistically significant (chi2 =17.7; p=0,00003). No promoter hypermethylation of the studied gene was found in normal ovaries.

CONCLUSIONS: Reduced OPCMPL gene expression in ovarian cancer in comparison to normal ovaries could be related to the hypermethylation of promoter region. This epigenetic alteration may be the reason of gene silencing and the loss of suppressor function....

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Journal Article 2006; 27(4): 535-537 PubMed PMID: 17136019 Citation  Keywords:  Aged, Aged, 80 and over, Alzheimer Disease:complications, Cognition Disorders:etiology, Depression:etiology, Female, Humans, Hypothyroidism:complications, Male, Middle Aged, Thyroxine:blood,.   

: The role of thyroid function in Alzheimer's disease (AD) has been subject to a number of studies during the last years. We investigated the possible relationship between plasma levels of the biologically active free form of thyroxin (fT4) and cognitive function in 227 outpatients with mild to moderate Alzheimer s disease (AD) in a cross-sectional study design. A significant negative correlation was found between plasma fT4-levels and Mini-Mental state examination (MMSE) score (Spearman Rho = -0.14, p=0.04). When the lowest quartile of fT4-levels (<15.1 pmol/l) was compared to the highest quartile (>19.0 pmol/l), statistically significant lower mean MMSE-scores were seen in the group with the highest fT4-levels (p<0.05, ANOVA). The mean difference between the 1st and the 4th quartile of fT4 was 2.6 MMSE-score points. No correlations were found between plasma total T4-levels, plasma total T3-levels, plasma TSH-levels and the MMSE score (p>0.05). When fT4 quartile groups were compared for depression measured in the Geriatric Depression Score (GDS 15), a slightly higher score was seen in the 1s and 2nd compared to the 3rd and 4th quartile groups without reaching statistical significance (1st quartile of fT4: GDS 5.2 +/- 3.8; 2nd: 5.3 +/- 4.0; 3rd: 4.4 +/- 3.4; 4th: 4.5 +/- 3.8) pointing to a reverse correlation of fT4 levels and depressive mood. This study leads to the conclusion that high levels of plasma fT4 might result in a worsening of cognitive impairment and a positive effect on depressive mood in AD....

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Journal Article 2006; 27(4): 517-522 PubMed PMID: 16892003 Citation  Keywords:  Adenocarcinoma:metabolism, Aged, Aged, 80 and over, Antibody Specificity, Cell Nucleus:metabolism, Cytoplasm:metabolism, Humans, Immunohistochemistry, Male, Middle Aged, Prognosis, Prostate:metabolism, Prostatic Hyperplasia:metabolism, Prostatic Neoplasms.   

BACKGROUND: Ubiquitin is a low molecular weight protein which has been detected in a variety of normal and cancerous tissues. It is involved in many regulatory processes including protein proteolysis. It has been implicated in tumor pathogenesis. The role of ubiquitin in human prostate gland is investigated in this study.

METHODS: In this study, we utilized immunohistochemistry technique to localize ubiquitin in human prostate gland and correlate it with different pathological conditions of the prostate.

RESULTS: Ubiquitin was localized in normal, benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma with variations in the distribution and intensity. In BPH, ubiquitin immunoreactivity was localized mainly in the nuclei while in the adenocarcinoma was localized mainly in the cytoplasm.

CONCLUSION: The presence of ubiquitin mainly in the nuclei and in the cytoplasm of BPH and prostatic adenocarcinoma, respectively, may suggest a role of ubiquitin in the development of the above mentioned conditions. Ubiquitin could be used as a potential marker for the diagnosis and prognosis of pathological conditions of the prostate....

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Journal Article 2006; 27(4): 473-481 PubMed PMID: 16891998 Citation  Keywords:  Adolescent, Adult, Anxiety:drug therapy, Cognitive Therapy, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Male, Middle Aged, Moclobemide:therapeutic use, Monoamine Oxidase Inhibitors:therapeutic use, Patient Dropouts, Phobic Disorders:drug.   

: The aim of the study was to assess the 6-months treatment efficacy and 24-month follow up of three different therapeutic programs (A. moclobemide and supportive guidance, B. group cognitive-behavioral therapy and pill placebo, and C. combination of moclobemide and group cognitive-behavioral therapy) in patients with a generalized form of social phobia. Eighty one patients (38 males and 43 females) were randomly assigned to three different therapeutic programs. Patients were regularly assessed on a monthly basis by an independent rater on the LSAS (Liebowitz Social Anxiety scale), CGI (Clinical Global Impression) for severity and change and BAI (Beck Anxiety Inventory). Altogether, sixty-six patients completed the six month treatment period and 15 patients dropped out. All therapeutic groups showed significant improvement. A combination of CBT and pharmacotherapy yielded the most rapid effect. Moclobemide was superior for the reduction of the subjective general anxiety (BAI) during the first 3 months of treatment, but its influence on avoidant behavior (LSAS avoidance subscale) was less pronounced. Conversely, CBT was the best choice for reduction of avoidant behavior while a reduction of subjective general anxiety appeared later than in moclobemide. After 6 months of treatment there were best results reached in groups treated with CBT and there was no advantage of the combined treatment. The relapse rate during the 24-month follow up was significantly lower in the group treated with CBT in comparison with the group A. formerly treated with moclobemide alone....

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Journal Article 2006; 27(4): 445-452 PubMed PMID: 16891997 Citation  Keywords:  Adult, Aged, Aged, 80 and over, Aging:immunology, Antioxidants:metabolism, Carcinogens:pharmacology, Circadian Rhythm:immunology, Female, Flow Cytometry, Granulocytes:drug effects, Humans, Infant, Newborn, Male, Middle Aged, Monocytes:drug effects, Oxidat.   

OBJECTIVES: In the present paper the circadian variation and age differences in human leukocyte reactive oxygen species (ROS) levels and plasma total antioxidant status were studied. Different ROS levels could influence disease during ageing and at different times of the day/night.

METHODS: Unstimulated and stimulated (12-O-tetradecanoyl-phorbol-13-acetate (TPA) blood samples were analysed by flow cytometry using dihydroethidium (DHE) and dihydrorhodamine 123 (DHR) as probes. 60 healthy individuals were divided into five equal groups ((I) 1-2 days post partum, (II) 20 +/- 2 years, (III) 40 +/- 2 years, (IV) 60 +/- 2 years and (V) 80 +/- 2 years) and 6 healthy volunteers were followed with blood samples at 3 hour intervals for 24 hours.

RESULTS: We observed a significant peak of ROS levels in both monocytes and granulocytes at 6 pm and 3 am using DHE as probe. DHR showed in principle the same pattern. The monocytes (unstimulated and stimulated) and unstimulated granulocytes of the newborn group showed higher ROS values than all the other groups, whereas the groups of adults did not differ from each other. The plasma total antioxidant status was significantly higher in the newborn group and showed no circadian variation.

CONCLUSIONS: The present data show that there is a circadian variation of ROS production in leukocytes that might possibly influence the occurrence of cardiovascular incidents like myocardial infarction. No increase in ROS production was found in healthy elderly compared to younger individuals. The increased ROS levels and antioxidant status of newborns might influence neonate immunity and play a part in cell signalling and development....

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