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Journal Article 2003; 24(3-4): 181-184 PubMed PMID: 14523354 Citation  Keywords:  Adult, Biomarkers, Circadian Rhythm:physiology, Humans, Male, Melatonin:blood, Psychiatric Status Rating Scales, Schizophrenia:blood, Schizophrenic Psychology,.   

OBJECTIVE: Aim of this study was to verify if a simple index as night-day plasma MLT level variation is able to confirm the existing data on circadian melatonin alterations in schizophrenia and if a relationship to disease itself instead of the actual clinical state can be suggested.

SETTING AND DESIGN: Ten consecutively admitted male schizophrenic inpatients were examined.

METHODS: The blood samples for melatonin were collected at 3.00 a.m. and 15.00 p.m. and consequently calculated the values of Delta () (MLT h.3.00- MLT h.15.00). We divided the sample into two subgroups: < 30 pg/ml and > 30 pg/ml taking 30 pg/ml as an arbitrary value, based on literature data, that should indicate a physiologically correct value of.

RESULTS: The 70% of the sample was under the 30 pg/ml value of (13.61 +/- 4.0) or was lacking of the characteristic circadian pattern of MLT secretion, whilst the 30% of the sample was over the 30 pg/ml value of (83.60 +/- 16.34) or was in presence of the characteristic circadian pattern of MLT secretion (p=.0001). No correlation was found between values and the scale and subscales scores for the assessment of psychopathology.

MAIN FINDINGS: The data confirm the lack of the characteristic circadian pattern of MLT secretion in schizophrenics.

CONCLUSION: The absence of significant correlation between night / day melatonin level differences and actual psychopathology variables should indicate that the suppression of is mostly related to the disease and independent from the clinical state. A neuroleptic-treatment effect cannot be excluded so far....

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Journal Article 2003; 24(1-2): 28-32 PubMed PMID: 12743528 Citation  Keywords:  Adult, Coloring Agents, Female, Fetus:anatomy & histology, Gestational Age, Humans, Portal Vein:anatomy & histology, Pregnancy, Reference Values, Umbilical Veins:anatomy & histology,.   

OBJECTIVES: The morphology of region umbilical vein, umbilical sinus and ductus venosus of human fetuses have been investigated.

MATERIAL AND METHODS: 26 human fetuses between 20 and 40 weeks' gestation were examined by morphological methods. The umbilical vein, DV and the portal vein were obtained after termination of gestation. Tissue samples have been fixed in phormaldehyde solution (pH 7,2) and were embedded in paraffin. The paraffin sections (5-7 micro k) were stained with hematoxylin and eosin, silver impregnation by Bilchovski, orcein, pikrofuchsin. Measurement of the angle between ductus venosus and the portal vein was obtained with alidade.

RESULTS: Anatomical scheme of the region of umbilical vein, umbilical sinus and DV indicating two different patterns. The first: DV has situated into line with umbilical vein (22 cases). The second: umbilical vein has rotated before umbilical sinus, forming the turn in right (4 cases). The double-layer wall of ductus venosus (DV) contained the elastic, collagen and argyrophilic fibers. Around isthmus region of DV vasa vasorum and nervi vasorum have been found. The specific anatomical finding of the ductal isthmus was an accumulation of smooth muscle cells as intimal pillow, which were protruded into the vascular lumen. The double-layer wall of portal sinus (intima and adventitia) have been as the internal elastic membrane. The smooth muscle cells have been revealed in the walls, were not formed the tunica media at term 20-40 weeks of gestation. By the contrast the umbilical vein showed multiple, circularly running smooth muscle bundles. In this study, the ductal thickness was consistently bigger in the inlet than in the outlet. The tunica adventitia was greatest in the junction with the portal sinus and the inferior vena cava compared with the part arranged in the liver parenchyma. The wall thickness of the portal sinus and of the umbilical vein was significantly higher than of the duclal wall.

CONCLUSION: The vascular muscle-elastic cells of intimal hyperplasia ("intimal pillow") in wall of DV, probably, executes the role of the fortification of resistant behaviours of vessel wall in connection with DV and portal sinus with high hemodynamics load in this area. The maximum thickness of adventicia in the field of joints also witnesses an hemodynamic in favour of particularities. The angle between DV and left branches of portal vein in dominate cases was sharp and right that reflects the general regularity of architectonics of the vascular riverbed....

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Journal Article 2003; 24(1-2): 21-27 PubMed PMID: 12743527 Citation  Keywords:  Acromegaly:drug therapy, Animals, Antineoplastic Agents, Hormonal:therapeutic use, Endocrine Gland Neoplasms:drug therapy, Hormone Antagonists:therapeutic use, Humans, Receptors, Somatostatin:drug effects, Somatostatin:analogs & derivatives,.   

: At the present time only two long-acting somatostatin (SS) analogs, octreotide and lanreotide, are commonly used in the routine therapy. Both analogs have a high affinity mainly to a somatostatin receptor subtype 2 (SSTR2). The established indications for SS analogs treatment include acromegaly, neuroendocrine tumors of the pancreas and gastrointestinal tract, and some gastro-enterologic diseases (pancreatitis, gastrointestinal bleedings, refractory diarrheas, pancreatic and intestinal fistulas). The recent investigations allow to predict the enlargement of therapeutic applications of SS analogs. It concerns pituitary tumors other than somatotropinoma, tumors of other endocrine glands like thyroid and adrenal gland, as well as some non-endocrine tumors. The progress depends on the introduction of new SS analogs with high affinity for SS receptor subtypes other than SSTR2, because some tumors present the high expression of SSTR1 (e.g. prostatic cancers) or SSTR5 (e.g. colonic cancers). Great hopes are connected with the coupling of SS analogs with the radioactive isotopes or non-radioactive cytotoxic agents to destruct the neoplastic cells highly expressing the specific subtypes of SS receptors. The pre- or postoperative in vivo imaging of SS receptors by means of the receptor scintigraphy, as well as the post-operative identification of SS receptor subtypes in the excised tumor tissues using immunohistochemistry, should play an important role in the prediction of the effects of SS analog treatment. Beside oncology, new therapeutic applications of SS analogs could be presumed among others in ophthalmology; it concerns the treatment of progressive Graves-Basedow ophtalmopathy, diabetic retinopathy, glaucoma and corneal diseases connected with corneal vascularization....

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Clinical Trial 2002; 23(5-6): 440-441 PubMed PMID: 12500167 Citation  Keywords:  Adult, Brain:diagnostic imaging, Female, Graves Disease:metabolism, Humans, Ligands, Male, Middle Aged, Receptors, Somatostatin:biosynthesis, Sample Size, Sex Factors, Somatostatin:analogs & derivatives, Tomography, Emission-Computed, Single-Photon,.   

: Animal experiments and observations in human brains have convincingly shown that sexual differentiation not only concerns the genitalia but also the brain. This has been investigated also in the light of a possible explanation of a presumed biological aetiology of transsexuality. The volume of the central subdivision of the bed nucleus of the stria terminalis, a brain area that is essential for sexual behaviour, has been reported to be larger in men than in women. Additionally, the number of somatostatin expressing neurons in this region was shown to be higher in men than in women. As neuronal production of somatostatin is involved the idea is striking whether somatostatin-receptor density in the cortex of cerebral hemispheres might be related to gender identity. We investigated in vivo the density of somatostatin-receptors in selected regions of the human brain in both sexes by means of receptor scintigraphy. Basal ganglia tracer uptake of 111-In-Pentreotide was equally low in both genders at 0,80% +/ 0,26 (related to tracer uptake of the whole brain layer). Temporal cortex accumulated at 2,9% +/ 1,1 in men and at 2,3% +/ 0,76 in women. Frontal brain region had an uptake of 3,0% +/ 1,4 in male and of 2,5% +/ 1,3 in female. This shows a tendency in males for relatively augmented uptake indicating higher somatostatin receptor density in temporal and frontal cerebral cortex....

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Journal Article 2002; 23(5-6): 427-431 PubMed PMID: 12500164 Citation  Keywords:  Adolescent, Causality, Child, DDT:adverse effects, Environmental Exposure:adverse effects, Environmental Pollutants:adverse effects, Female, Germany:epidemiology, Global Health, Humans, Insecticides:adverse effects, Intelligence Tests:statistics & numeric.   

OBJECTIVES: To investigate a possible lasting impact of dichlorodiphenyl trichloroethane (DDT) exposure in neonatal life on mental capacities in later life.

MATERIAL AND METHODS: Relationships were evaluated by correlation and regression analysis between total DDT concentrations in human breast milk in the years of birth (1984/1985) and measurements of mental capacities obtained in pupils of the PISA 2000 studies as well as percentages of backward children in Germany in 1994/95.

RESULTS: Comparing total DDT levels in human milk during the years of birth (1984/85) evaluable for eleven PISA countries with assessed mental capacities of 15-year-old pupils of PISA International, a significant inverse correlation was found (p < 0.001), even after adjustment for socioeconomic statuses (p = 0.001). Furthermore, a significant inverse correlation (p < 0.001) was also obtained between the total DDT concentrations in human milk in 1984/85 in ten foreign countries of three continents plus fourteen Federal States of Germany and the mental capacities of 15 year-old pupils of PISA International plus PISA National (Germany) 2000. Finally, a significant positive correlation was observed between total DDT contents in human milk in 1984/85 and the percentages of backward school children in 1994/95 in Federal States of Germany (p < 0.001).

CONCLUSIONS: These data in association with additional experimental and epidemiological findings suggest that DDT is a "neuroendocrine disrupter" as well as a "functional teratogen" leading to harmful effects on brain development and mental capacities in later life. Thus, a neuroendocrine prophylaxis during critical developmental periods in early life as recommended by our group since many years appears to be most important for primary preventive medicine but even for "preventive pedagogics". The validity of these theses should be re-tested in future PISA studies....

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Journal Article 2002; 23(Suppl 1): 45-49 PubMed PMID: 12019351 Citation  Keywords:  Antioxidants:pharmacology, Cell Cycle:drug effects, DNA:metabolism, Electrophoresis, Flow Cytometry, Humans, Male, Melatonin:pharmacology, Mutation:genetics, Prostatic Neoplasms:metabolism, Receptors, Androgen:drug effects, Response Elements:drug effects,.   

OBJECTIVES: The pineal hormone melatonin inhibits the growth of benign human prostate epithelial cells and the androgen-dependent prostate cancer LNCaP cells. In the androgen-nonresponsive prostate carcinoma PC3 cells melatonin inhibits cell growth only at high but not low cell density. We have recently found that melatonin causes nuclear exclusion of the AR and attenuates it transcriptional activity in LNCaP cells as well as PC3 cells stably transfected with a wild type AR expressing vector (PC3-AR). The aim of this study was to investigate whether melatonin inhibits effects of AR on cell growth in PC3-AR cells and whether inhibition of AR DNA binding is involved.

METHODS: The effects of androgen, melatonin and their combination on the growth of the PC3-AR cells and on AR DNA binding in PC3-AR and LNCaP cells were studied.

RESULTS: DHT suppressed cell growth in the PC3-AR cells and enhanced AR binding to the androgen responsive element (ARE). Melatonin had no effect on cell growth in the absence of DHT but counteracted the androgen-induced inhibition at low androgen concentrations. Melatonin did not suppress and even slightly enhanced the capacity of AR binding to the ARE in the PC3-AR as well as in LNCaP cells.

CONCLUSIONS: Attenuation by melatonin of AR activity in the prostate cancer cells is not due to suppression of AR binding to the ARE, and is presumably caused by its effects on AR protein interaction and intracellular trafficking....

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Journal Article 2002; 23(2): 155-160 PubMed PMID: 12011802 Citation  Keywords:  Aged, Aged, 80 and over, Alzheimer Disease:blood, Estradiol:blood, Estrone:blood, Female, Folic Acid:blood, Humans, Logistic Models, Mental Status Schedule, Testosterone:blood,.   

OBJECTIVES: In vitro and in vivo animal studies suggest that sex steroids, such as estrogens and testosterone, could protect the brain. However, estrogen replacement therapy (ERT) for Alzheimer's disease (AD) in women has not been successful. We hypothesised that the lack of effect of ERT might be related to an interaction between estrogens and some other factor(s) associated with AD.

DESIGN, SETTING AND METHODS: We analysed total estrogen (TE) and testosterone (TT) levels in women diagnosed with AD and controls of the Oxford Project To Investigate Memory and Ageing. Because estradiol (TE2) after the menopause is largely derived from estrone (TE1), we computed the ratio TE2/(TE1+TE2) and a total steroid index (TT+TE2+TE1).

RESULTS: Women with AD (n=66) had significantly higher levels of TE2 (27+/-13 vs. 21+/-13) and a higher TE2/(TE1+TE2) ratio. Stepwise logistic regression analyses showed that the TE2/(TE1+TE2) ratio was the main sex steroid predictor for AD (O.R.=1.06, 95% C.I.=1.01-1.11, p<0.01). Multiple regression analyses revealed that dementia severity was associated with an interaction between the TE2/(TE1+TE2) ratio and serum folate (B=4.59 (SE=1.48), beta=1.22, 95% C.I.=1.62-7.56, p<0.005). None of the other potential mediators of this association (body mass index, sex hormone binding globulin, homocysteine levels, ApoE genotype, smoking, diabetes, blood pressure) was significant.

MAIN FINDINGS: A high ratio of estradiol to total estrogens is associated with AD but, in subjects with a high ratio, the dementia severity was lower in those with high serum folate levels.

CONCLUSIONS: If this association is causal, then supplementation with folic acid might be considered in future studies on ERT in AD....

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Clinical Trial 2002; 23(1): 61-63 PubMed PMID: 11880864 Citation  Keywords:  Aged, Androgen Antagonists:therapeutic use, Anilides:therapeutic use, Humans, Levodopa, Male, Middle Aged, Nitriles, Prolactin:blood, Prostatic Neoplasms:blood, Tosyl Compounds,.   

OBJECTIVES: The secretion of prolactin (PRL), which is a growth factor for prostate cancer cell proliferation, has been proven to present profound alterations in advanced prostate cancer patients, consisting of abnormally elevated baseline levels and paradoxical response to L-dopa. Moreover, the efficacy of standard therapies for prostate cancer may be mediated at least in part by changes in PRL secretion. The present study was carried out to analyze the effects of the new antiandrogen agent bicalutamide on basal levels of PRL and on its response to L-dopa in metastatic prostate cancer patients.

MATERIAL & METHODS: The study included 10 metastatic prostate cancer patients. They were treated with bicalutamide at a dose of 50 mg/day orally. They were investigated with L-dopa test before therapy and after one month of treatment. L-dopa was given orally at 500 mg, by collecting blood samples before and at 60, 120 and 180 minutes after L-dopa administration. Serum levels of PRL were measured by the RIA method.

RESULTS: Abnormally basal levels of PRL were seen in 4/10 (40%) patients. Mean PRL basal levels decreased after bicalutamide therapy, without, however, significant differences. Before therapy, a paradoxical increase in PRL levels after L-dopa occurred in 4 patients, 3 of them showed basal concentrations of PRL within the normal range. Moreover, bicalutamide therapy significantly reduced PRL increase in response to L-dopa.

CONCLUSIONS: This study would suggest that the measurement of the only basal levels is not sufficient to define as normal the secretion of PRL in advanced prostate cancer, because of the possible existence of altered response to the dynamic tests for PRL secretion. Moreover, the study shows that the antitumor therapy with the new anti-androgen bicalutamide may reduce PRL secretion and improve its paradoxical secretion in response to L.-Dopa. Further studies will be required to better define the possible prognostic impact of changes in PRL secretion on the efficacy of treatments for metastatic prostate cancer....

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