ACTA ENDOCRINOLOGICA (BUC)

Alzheimer’s disease(AD) is the leading cause of dementia and is characterized by the presence of extensive plaque deposition and neurofibrillary pathology. The aim of the present study was to make an update regarding the influence of estrogens and SERMs on inflammation and on the resolution of inflammation, respectively, focusing on these most important features implicated in the pathophysiology of AD. Several hypothesised mechanisms of action of estrogens and SERM are exposed and also some relevant clinical studies on this subject are analysed. The analyzed studies have a high heterogeneity of preparations used, of administration routes, of the female population included and of the periods of time from the appearance/ induction of menopause to the therapeutic intervention and also of follow-up periods of patients and of the means of evaluating their cognitive decline. One can say that all the ways of pharmacological influence on the membrane or intracellular signalling system associated to estrogens that may have clinical importance in the prevention and possibly in the treatment of AD have not been exhausted. Estrogens with selective ERα or G protein-coupled estrogen receptors (GPER1 or GqMER) effects could be used to influence the resolution of inflammation process, with positive effects on AD evolution.

The beta 3 agonists have antiobesity, thermogenetic and lipolytic properties. Starting from BRL35135 structure, a well-known beta 3 agonist, 3 new phenylethylamine derivates (A, B, C) and 2 new pyrazol derivates (D, E) were synthesized.\r\nPurpose. The aim of this study was to evaluate the effect of five new compounds derived from of BRL35135 on glycemia in normal and diabetic rats.\r\nMethods. For each experiment, test and control groups of 6, 8 or 10 male Wistar rats were used. For inducing experimental diabetes mellitus, alloxan (100 mg/kg body weight) was intravenously injected. Tested substances were intraperitoneally injected (1 or 100 mg/kg body weight) and glycemia values were measured before and at 3 hours after their administration. Control groups received propyleneglycol, the solvent of the new compounds. Glycemia values were measured with a calibrated glucometer.\r\nResults. In normal rats one of the phenylethylamine compounds (substance C) (100 mg/kg body weight) had a hypoglycemic effect comparative to control (p=0.03). In glucose tolerance test, substance E (100 mg/kg body weight) stopped the increase of glycemic values determined by glucose oral administration in the first 60 minutes comparative to control (p=0.03). In the alloxanic diabetes model, before insulin administration the substances hypoglycemic effect could not be measured with the glucometer because of very high values of glycemia. After insulin administration no significant differences between the treated and the control groups were registered. Further studies on the hypoglycemic effect of substances C and E are needed in order to establish their possible antidiabetic effect.\r\nConclusion. A phenylethylamine derivate and a pyrazol derivate of BRL35135 had a hypoglycemic effect in normal rats, but this effect could not be confirmed in rats with alloxanic diabetes.

Aims: To assess if amiodarone maintains its antiarrhythmic efficacy in the presence of amiodarone-induced hyperthyroidism (AIT) and to identify the tri-iodothyronine (T3) threshold for atrial fibrillation in patients with AIT versus common hyperthyroidism.\r\nPatients and methods. Study group A consists in 49 patients (25 M/24 F) with AIT (220.83 ? 71.33 mg/day along 2.36 ? 2.25 years) and severe cardiopathies (9 valvulopathies, 40 ischaemic, dilatative and hypertensive cardiomyopathies), aged 57.87?12.63 years. Control group B consists in 51 hypothyroid (B1) or euthyroid patients (B2) treated with amiodarone (222.55 ? 68.78 mg/day along 2.67 ? 1.84 years) and also in 100 patients (23M/77F) with overt hyperthyroidism (B3), without major heart diseases, aged 52.74?12.85 years; TSH, total T3, total T4, free T4 were measured by radioimmunoassay. All were clinically, ECG and echocardiography evaluated.\r\nResults. Prevalence of arrhythmias recurrence was 59.2% (29/49 patients) in group A, significantly higher than in each control subgroups B: B1- 28% (7/25), B2- 15.45% (4/26) and B3- 20% (20/100), P< 0.001. Patients from study group A with AIT and T3 levels >250 ng/dL developed significantly more frequent atrial fibrillation (p= 0.04). However, in control group B3 with common hyperthyroidism, no T3 threshold for arrhythmias could be identified. Overall, there were no significant differences in total T3 levels with respect to the presence of atrial fibrillation in both study group A and subgroup B3 with common hyperthyroidism (p=ns).\r\nConclusion. Amiodarone antiarrhythmic efficacy is surpassed in AIT by the increased arrhythmic susceptibility of damaged myocardial tissue to minimally increased thyroid hormones levels. A tri-iodothyronine level > 250 ng/dL superimposed on preexistent proarrhythmic substrate in amiodarone-induced hyperthyroidism should be avoided.

Background. Malignant melanoma is the most aggressive form of skin cancer with a rapidly increasing incidence rate. In contrast to other tumors, the role of sex steroid hormones\r\nin the initiation and progression of melanoma remains unclear.\r\nObjective. To assess the interaction between the content and composition of gangliosides and sex steroid hormones 17&#946;-\r\nestradiol (E2) and testosterone (T) in malignant melanoma.\r\nPatients and methods. The analysis included 45 melanoma patients (age 28-86; 14 men, 15 non -pregnant women in mid\r\nfollicular phase and 16 postmenopausal women) and 46 healthy controls. Serum levels of gangliosides (GM1-3, GD1a,b,2,3, GT1b, GQ1b), estradiol, testosterone measured in serum by chromatographic and immunochemiluminescence methods were correlated with sex and age.\r\nResults. Steroid hormones levels showed no differences between groups (p>0.05), while total gangliosides in normal\r\nserum were significantly lower than total ganglioside concentrations determined in melanoma samples (18.63 ? 3.17 mg/dL versus 74.82 ? 34.56 mg/dL) (p<0.05). There were no differences related to sex or age within groups regarding total gangliosides levels. Gangliosides pattern in\r\nmelanoma patients compared to control showed lower GM3, higher GD3, lower GM3/GD3 ratio, increased GD2 levels, and\r\nno significant variation of GM1, GM2, GD1a, GT1b gangliosides. There is a positive correlation between estradiol levels and total gangliosides concentration both in non-pregnant premenopausal and postmenopausal melanoma patients. GM3 is negatively correlated with estradiol levels in melanoma group, GT1b and O-Acetyl GD3 concentrations are positively correlated with estradiol levels in women with melanoma. Testosterone levels showed no significant\r\ncorrelation with the content and pattern of gangliosides in melanoma patients.\r\nConclusions. The correlations between content and composition of gangliosides and estradiol in melanoma suggest a possible role of these molecules in melanoma behavior.

Context. Adipokines secreted by fat cells are vital to the control of energy metabolism, communicating the nutrient status with the tissues responsible for controlling both energy intake and expenditure and insulin sensitivity. Objective. We aimed to prove in an experimental animal study that maternal obesity has long term adverse fetal metabolic consequences, which pass on even to the next generation of descendants. Design. The effects of maternal obesity have been studied on animal model using 50 obese female Wistar rats, in which we induced obesity by high-calorie high-fat diet administered by gavage. Subjects and Methods. Obese rat females were sacrificed at gestation term and we analyzed the secretion of adipokines from maternal venous blood: leptin and adiponectin, placental, pancreatic, liver and brain homogenates lipid peroxidation levels estimated by: MDA (malonyl-dialdehyde), total thiols and GSH – as antioxidant factors and routine biochemistry. Results. Low levels of adiponectin and increased levels of leptin positively correlated with the value of placental and fetal tissue lipid peroxidation (from the liver, pancreas and brain) measured by elevated MDA and total thiols and low levels of GSH. The lipid peroxidation in the organs examined generated consistent results, showing high levels of peroxidation expressed through high values of MDA in the groups with Omega 6 supplements respectively no supplementation, and low levels of antioxidants expressed through glutathione and thiols. Conclusions. Endocrine secretion of adipokines from the adipocytes and the recruited macrophages of obese mothers is positively correlated with placental and tissue lipid peroxidation level and routine biochemical parameters.