Association of serotonin transporter gene polymorphism 5HTTVNTR with osteoporosis.

AIM: To study the association of serotonin transporter gene polymorphisms and osteoporosis. MATERIAL AND METHODS: Blood samples were collected from 186 individuals with normal bone mineral density and 89 with osteoporosis. Serotonin transporter gene polymorphisms 5HTTVNTR and 5HTTLPR were studied by PCR and statistical analyses used to test the association between groups. RESULTS: The frequency of 12/10 and 12/12 genotypes of 5HTTVNTR was significantly higher among the osteoporotic patients (OR=2,620 CI 95% [1,112--6,172], P=0,037). For 5HTTLPR we did not find significant differences between the two studied groups. CONCLUSIONS: As far as we know, this is one of the few studies that report an association between 5HTTVNTR and osteoporosis opening the hypothesis that the determination of this specific serotonin transporter gene polymorphism may contribute to the identification of individuals at high risk for the development of osteoporosis.

Cytochrome P450 1A1 (CYP1A1) T6325C polymorphism might modulate essential hypertension-associated stroke risk.

Stroke is a serious complication associated with hypertension. Because cytochrome P450 1A1 (CYP1A1) is involved in the production of arachidonic acid-derived vasoactive substances, we hypothesized that CYP1A1 functional polymorphisms (linked to changes in enzyme activity) might be related to pathological conditions associated with essential hypertension. We genotyped 32 patients with hypertension for three CYP1A1 polymorphisms, and individuals with or without history of previous stroke were compared. These results were also compared with a control population sample of 152. The distributions of T6235C (m1) CYP1A1 genotypes in patients with (TT: 44.4%; TC/CC: 55.6%; n = 9) and without stroke (TT: 82.6%; TC/CC: 17.4%; n = 23) indicate that the C allele is associated with stroke (OR = 5.94; 95% C = 1.46 - 24.23). No association was found between the polymorphism studied and essential hypertension. Our results suggest a relationship between CYP1A1 activity and incidence of stroke in patients with essential hypertension, but no conclusion can be drawn regarding an association with essential hypertension.

[Significance of family assessment and biological markers in the prevention of arterial hypertension]. / Importância da avaliação familiar e marcadores biológicos na previsão da hipertensão arterial.

OBJECTIVE: To verify the predictability of the appearance of hypertension through the clinical history and biological markers. POPULATION: Consisted of 300 Portuguese Caucasian individuals, M = 130 and F = 170, between the ages 18 and 85, including 90 pregnant women. METHODS: Blood pressure was measured in every individual, and questions were made concerning personal and familiar hypertensive background. The serum renin activity, the active renin, serum endoxin, and the urinary aldosteron, free dopamine, c--AMP, and noradrenalin were checked. The analysis of the results was carried ou using the Student's T Test and de chi(2) method. RESULTS AND CONCLUSIONS: Hypertensive parents lead to the development of hypertension on their descendants; the averages of diastolic blood pressure in normotensive individuals are higher when parents are hypertensive, compared with normotensive, seeming that a possible genetic factor may be implied in the involvement of the vessels. Normotensive young masculine adultshave higher average systolic blood pressure when their fathers are hypertensive, than those whose fathers have normal blood pressure levels; as far as young women are concerned, we verified that the mother's genetic influence seems to be relevant in the appearance of higher blood pressure levels in their daughters during pregnancy, contributing to think hat man and women may have genetically different factors to determine blood pressure levels. We also verified that young adults with normal levels of blood pressure, whose parents suffer from high blood pressure, present significantly higher levels of serum renin activity than a similar group of young adults whose parents have normal blood pressure. We concluded that the family history and the measuring of the blood pressure even at young adults may contribute for the forecasting of high blood pressure, as is the evaluation of biological parameters, particularly in those who have family history of hypertension. Serum renin activity may be a possible biological marker for the forecast of the future development of high blood pressure.

[Reduced and oxidized glutathione of the placenta in pregnancy complicated by pre-eclampsia]. / Glutatião reduzido e oxidado da placenta na gravidez complicada com preeclâmpsia.

Significative enhancement of free radical formation (FRO) in vivo is an important feature of hypertensive disorders of pregnancy (HDP), namely preeclampsia (PIH). The latest investigations about the pathology of HDP, showed the contribution of placental circulation to the development and evolution of such disease. The placental bed can be a potential source of FRO or activation of cells that can produce FRO. Glutathione, is an important molecule for cellular protection against damage, is a cofactor of many enzymes, in particular, for the glutathione peroxidase of the placental tissue; this enzyme in the placenta bed prevent the production of thromboxan and lipoperoxides; the latter are potentially damaging to the endothelium cells and can cause vasoconstriction, the most important feature of PIH. The activity of that enzyme is deficient in PIH. We studied, by fluorometric assay, the concentrations of the two states of glutathione in placental homogenates (PLH) from pregnant women without pathology (PWN) and from pregnant women with PIH (PWPIH). The data showed significant low concentrations in the PLH of the two states of glutathione in the PWN against high concentrations of this molecule in the PLH from PWPIH. This feature can result from a deficient user of the glutathione by the cellular mechanism for prevention against oxidative factors. In addition, our study shows a biochemical marker that is suggestive that the placental bed is a potential source of FRO production in PIH.

Activation of a NADH dehydrogenase in the human erythrocyte by beta-adrenergic agonists: possible involvement of a G protein in enzyme activation.

NADH dehydrogenase in the plasma membrane transfers electrons from NADH to external oxidants like ferricyanide, through pathways which are linked to metabolic processes in the cell. Hormone binding to specific sites (receptors) can modify the enzyme activity, suggesting a direct or indirect coupling between the redox system and the hormone receptors. Reduction of external ferricyanide to ferrocyanide by human erythrocytes was stimulated by beta-adrenergic agonists (adrenaline, ritodrine and isoxsuprine), this effect being dependent upon concentration and pH. The agonist-stimulatory effect was attenuated in the presence of metoprolol (10(-4) M), a beta-adrenergic antagonist, and was not modified in the presence of prazosin, an alpha-adrenergic antagonist, suggesting that modification of the redox activity is mediated by binding of the agonists to beta-adrenergic receptors present in the human erythrocytes. Basal and agonist-dependent activities were inhibited in the presence of sulfhydryl reagents p-chloromercuribenzoate (PCMB, 10(-5) M) and N-ethylmaleimide (NEM, 10(-3) M), indicating the involvement of -SH groups. Inactivation by NEM was reversed by washing the cells with GTP (10(-3) M) and GTP gamma S (10(-4) M), suggesting that the specific alkylated -SH group(s) is located on a G protein in the hormone-receptor-G-protein complex. The human erythrocytes contain G proteins, displaying both guanine-nucleotide-binding properties and GTPase activity. Fluoride (10(-2) M) and fluoroaluminate (AlF4- (F-, 10(-2) M + Al3+, 10(-5) M), G protein activators, enhanced the basal and agonist-dependent activities, suggesting the involvement of G proteins in this system. The overall results indicated that one of the coupling components between the hormonal receptors and the redox system is probably a G protein, and the mechanism of enzyme activation after hormone binding to the receptor is based on the redox state of cysteine residues probably within the receptor-G-protein complex.

Effect of an aerobic training on magnesium, trace elements and antioxidant systems in a Down syndrome population.

The aim of the present study was to determine the effect of an aerobic training on plasma and red blood cells' levels of magnesium, copper, selenium and zinc and on some oxidative stress parameters in a Down syndrome (DS) sample population. Sixteen young male adults with DS participated in the protocol. Among them, eight were randomly assigned to the control group and the remaining eight participated in a 16 week training programme consisting of 10 min warm-up followed by an aerobic session at a work intensity of 60 to 75 per cent of VO2 peak lasting from 15 to 25 min, increasing 5 min every 5 weeks and by a 5 min cool-down period, 3 days/week. Blood was withdrawn by butterfly from antecubital vein of each subject at fast, 2 days before the beginning of the programme and 2 days after its ending. Before the training period, when comparing the two groups, no significant differences were observed in the evaluated parameters. However, when comparing with a healthy population, red blood cells magnesium and plasma and red blood cells selenium mean values were low in both groups and mean SOD activity was 1.4 times higher. After the protocol the mean values of the minerals studied did not show significant differences between groups except for plasma zinc that was lower (p = 0.029) in the trained group. Plasma TBARS increase was significant in the trained group (p = 0.034) but not in the control group and plasma GSH of the trained group had a significantly higher increase than the control group (p = 0.003). The levels of plasma TBARS after the training programme that were inversely correlated with red blood cells GSSG levels (p = 0.023) and the higher increase of plasma GSH mean values observed, may be explained by the effect of the exercise period on the peroxidation and reduction of glutathione and also on the synthesis and efflux of GSH. Red blood cells magnesium levels remained low after the training programme which is in accordance with other studies. Plasma zinc decreased during the programme could be related to the activated expression of antioxidant mechanisms after the training.

[Platelet serotonin as a biological marker of autism]. / Serotonina plaquetária como marcador biológico de autismo.

Platelet levels of serotonin were determined by a quantitative direct radioimmunoassay, in a group of autistic patients and a control group. Thirty six autistic patients (28 males and 8 females), all with severe mental retardation, and a group of 23 matched controls, were studied. The serotonin levels in autistic patients (mean +/- SD) (88.37 mmol/dl +/- 40.38) were significantly higher that in the control group (49.54 mmol/dl +/- 16.49). There were no significant differences in levels between the sexes and age groups among subjects in the patient and the control groups. We detected a hyperserotoninaemia in 70% of the autistic patients. We also discuss correlations between serotonin levels in our patients with known aetiologies and levels quoted in the literature and propose RIA to be used as a quick, easy and reliable method for the analysis of large numbers of samples.

Conversion of adrenaline to indolic derivatives by the human erythrocyte plasma membrane.

The conversion of adrenaline to aminochromes by the human erythrocyte plasma membranes at pH 9.5 was shown to be a complex reaction that proceeded at least by two distinct phases. The first one, corresponding to the formation of adrenochrome, is catalyzed in the presence of the membranes, suggesting the involvement of an enzyme-mediated process. Active oxygen species were identified as intermediates during this phase. Oxygen radical scavengers (catalase and superoxide dismutase) suggested H2O2 and O2- involvement. Adrenochrome formation was stimulated by NADH indicating the participation of another enzyme (NADH dehydrogenase) which is known to be present in the human erythrocyte plasma membrane. The second phase, corresponding to the disappearance of adrenochrome, is also stimulated by NADH and inhibited in the presence of the membranes. In this reaction, adrenochrome is converted to aminochromes via adrenochrome semiquinone. The formation of radical species is demonstrated by EPR spectroscopy. The results led to the proposal of a mechanism for the formation of adrenochrome and other oxidation products from adrenaline.

[Erythrocytic enzymatic systems and their antioxidative potential in pregnant women undergoing labor induction with intracervical PGE2]. / Sistemas enzimáticos eritrocitários e seu potencial antioxidante nas grávidas submetidas a indução do trabalho de parto com PGE2 intracervical.

Our purpose is to correlate, the apgar score of the new-borns from induction of labour (IL) with Prostaglandin E2 (PGE2) endocervical gel, and the oxidative environment of the pregnant woman during labour, studying biochemical markers of the erythrocytes. PGE2 is responsible for the regulation of the vascular response in pregnancy, namely for the vasoconstriction caused by Angitensin II. The production of Prostaglandins in vivo depends on mechanisms related to free radicals of oxygen (FRO). The production of FRO is enhanced in normal pregnancy. We have studied two erythrocytic enzymes and plasmatic concentration of PGE2 before and after the IL. Those enzymes are oxireductases-the transmembrane reductase (RTM) and the metahemoglobin reductase (MHR). Their function is to prevent the effects of the FRO on cellular biomolecules namely the endothelium and the red blood cells. This prevention of oxidative stress can facilitate the deformability of the erythrocytes, so these cells can easily transpose the small vessels and bind the oxygen to the tissues. The activity of those enzymes can be modulated by PGE2 used in the IL. We have not found significant variations on the activity of RTM after IL. The activity of MHR was enhanced with statistical significance, 30 minutes after the induction. This enhancement of activity can be a mechanism to prevent the oxidative stress of the induction of labour.

Membrane-mediated effects of catecholamines on the DNA of human leukocytes: the role of reactive oxygen species.

The effects of epinephrine and two other beta 2-adrenergic agonists, ritodrine and isoxsuprine, on the induction of damage to the DNA (production of strand breaks) in human leukocytes were studied by fluorescence analyses of unwinding DNA. Epinephrine stimulated the development of DNA strand breaks. Ritodrine and isoxsuprine inhibited this effect of epinephrine on the human leukocytes by competition for binding to receptors, but they were not oxidized to the same extent as epinephrine. Metoprolol, which acts predominantly as a beta 1-antagonist, demonstrated a beta 2-antagonism, as compared with epinephrine. Since the o-oxidation of epinephrine involves the production of damaging oxygen species such as O2-. and H2O2, we studied the effects on DNA of extracellular H2O2 in the presence and absence of epinephrine. Extracellular H2O2 induced significant damage to the DNA, but it had a smaller effect when applied with epinephrine. The results obtained with 3-amino-1,2,4-triazole, an inhibitor of endogenous catalase, were not significantly different from control results, under our experimental conditions. Nevertheless, this compound had a mitigating effect when applied with epinephrine. We also investigated the action of nicotinamide in the presence and absence of epinephrine. The results demonstrated the importance of nicotinamide in cellular oxidative stress. Two antioxidant enzymes, superoxide dismutase and catalase, inhibited the epinephrine-induced damage to DNA.

[The beta-adrenergic receptor]. / O receptor beta adrenérgico.

The Authors review the constitution and mechanism of action of the beta adrenergic receptor. It is part of a large family which includes visual pigments, muscarinic, serotonergic, olfactive and substance K receptors. Catecholamines given an electron to the receptor. It goes then successively to the alpha submit of Gs protein ant to adenylyl cyclase. The process of activation consists in a successive transfer of one electron.

[Endocrine arterial hypertension. Pheochromocytoma]. / Hipertensão arterial endócrina. Feocromocitoma.

The authors emphasize some embryologic features of the chromaffin tissue as a basis of understanding of both the physiopathologic and clinical aspects of Pheochromocytoma. The appropriate sequence of diagnostic procedures was established in order to obtain clinical, biochemical and anatomical evidence of the tumor. It was concluded that an early diagnosis is mandatory in order to plan a curative surgical therapeutic approach. The embryologic and biochemical understanding of the Pheochromocytoma, in the context of the neuroendocrine tumors, allows a better rationale both for the diagnosis and therapy of this condition.

Acetylation phenotypes in patients with bladder carcinoma.

The present study was done to evaluate the possible association of bladder carcinoma with the slow acetylator phenotype in a portuguese population. 49 patients with bladder carcinoma were compared to a normal control group of 84 individuals. No statistically significant association was detected. But when subdividing the group of slow acetylators it is found that in the subgroup with 12-36% acetylation there is a higher percentage of patients, which is statistically significant. These results are in agreement with two other studies, using populations of similar ethnic origin.