Brain and heart in hyperhomocysteinemia induced by methionine nutritional overload

Date: October 8th – 10th, 2015, Belgrade

Progesterone upregulates activity and protein expression of efecto-5'-nucleotidase in ischemic brain of male wister rats

Reduction of oxygen and glucose supply to the brain due to diminished cerebral blood flow leads to damage of tissue which in experimental conditions can be mimicked by permanent ligation of common carotid arteries (2VO). Besides numerous genomic and non-genomic processes, cerebral ischemia enhances expression of ecto-5'-nucleotidase (eN), a main enzyme in the central nervous system that produces potent neuromodulator and neuroprotector, adenosine. Since progesterone (P), a potent sex steroid, is recognized as neuroprotective, aim of this study was to examine whether repeated low-dose P treatment is capable to induce changes in activity and protein expression of eN, at rat cortical membrane fraction following 2VO. Obtained results indicate that P modulates investigated parameters and through stimulation of adenosine generation might promote cytoprotection in ischemic brain.Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-30 September 2016

Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover

Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury indiabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascularchanges in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visualcycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were dividedinto the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. groupexposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18).Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved inthe visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposurealleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascularAqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantlyup-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantlyhigher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via itsanti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression

Polycystic ovary syndrome: A contemporary clinical approach

Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women during the reproductive period. It is considered a complex metabolic disorder with long-term metabolic, as well as reproductive consequences. Main pathophysiological pathways are related to the increased androgen levels and insulin resistance. Nowadays, genetic origins of PCOS are acknowledged, with numerous genes involved in the pathogenesis of hyperandrogenemia, insulin resistance, inflammation, and disturbed folliculogenesis. Rotterdam diagnostic criteria are most widely accepted and four PCOS phenotypes have been recognized. Metabolic abnormalities are more common in phenotypes 1 and 2. Women with classic PCOS are more obese and typically have the central type of obesity, more prevalently displaying dyslipidemia, insulin resistance, and metabolic syndrome that could be associated with an increased risk of cardiovascular complications during life. Heterogeneity of phenotypes demands an individualized approach in the treatment of women with PCOS. Metabolic therapies involve a lifestyle intervention followed by the introduction of insulin sensitizers including metformin and inositols, glucagon-like peptide 1 receptor agonists (GLP-1 RA), as recently sodium-glucose cotransporter-2 (SGLT2) inhibitors. The addition of an insulin sensitizer to the standard infertility therapy such as clomiphene citrate improves ovulation and pregnancy rates. Our current review analyzes the contemporary knowledge of PCOS etiology and etiopathogenesis, its cardiometabolic risks and their outcomes, as well as therapeutic advances for women with PCOS. © 2021 Bentham Science Publishers

Age, body mass index, and serum level of DHEA-S can predict glucocorticoid receptor function in women with polycystic ovary syndrome

Glucocorticoid receptor (GR) transduces the glucocorticoid (GC) signal that could lead to metabolic derangements depending on the tissue responsiveness to GC. We aimed to investigate possible causative relation of the GR functional properties in peripheral blood mononuclear cells of women with polycystic ovary syndrome (PCOS), with their clinical and biochemical characteristics. Thirty women with PCOS [mean age: 26.5 +/- A 5.1 years, mean body mass index (BMI) 24.5 +/- A 5 kg/m(2)], and thirty respective controls were analyzed for the number of GR sites per cell (B (max)), apparent equilibrium dissociation constant (K (d)), and binding potency (GR potency). A strong association between B (max) and K (d) (r = 0.70, P < 0.0001), and GR potency with age (r = 0.49, P = 0.009) was observed in PCOS women. The multiple regression analyses within the PCOS group revealed that independent predictors for K (d) were BMI, total cholesterol, and dehydroepiandrosterone-sulfate (DHEA-S) (r = 0.58, P = 0.038), while for GR potency (r = 0.687, P = 0.013) were age, BMI, DHEA-S, and basal cortisol concentration. The results suggest that PCOS pathophysiology may be related to alterations of a cross stalk between glucocorticoid signaling, age, and metabolic parameters. These findings should be further explored in studies on the role of GR in PCOS-related metabolic derangements.Ministry of Science of Serbia [143003