Valproate and delta-sleep peptide display high efficacy against metaphit-induced audiogenic seizure in rats

The effects of valproate (VPA) and delta sleep -inducing peptide (DSIP) on metaphit -induced generalized, audiogenic seiz ure in adult rat males were compared. The animals were i.p. injected with : 1. Saline; 2. metaphit (mp, 10mg kg–1); 3. metaphit (10mg kg–1) and 8 h later with DSIP (0.1, 0.2, 0.4 or 1.0mg kg–1 ), 4. metaphit (10mg kg–1) and 8 h later with VPA (50, 75 or 100mg kg–1); 5. DSIP alone (1.0mg kg–1) and 6. VPA, alone (100mg kg–1). The rats were exposed to sound stimulation at hourly intervals and the behavior and EEG were analyzed. The EEG signals in metaphit rats appeared as a sleep -like pattern and spike -wa ve complexes with increased power spectra. Valproate and DSIP reduced the incidence of seizure and prolonged duration of latency in a dose -dependent manner. ED50 of valproate in the 1st hour after administration was 63.19mg kg–1 and that of DSIP 3.19mg kg–1 four hours after injection. This suggests that VPA, reached a peak of action immediately after the application, while DSIP had a prolonged action, mildly reducing, but not abolishing metaphit seizure. None of the applied VPA and DSIP doses eliminated the metaphit -provoked EEG signs of epileptiform activity

Brain and heart in hyperhomocysteinemia induced by methionine nutritional overload

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

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

Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation

Recent studies reported that exposure of juvenile rats to cranial irradiation affects hypothalamic-pituitary-adrenal (HPA) axis stability, leading to its activation along with radiation-induced inflammation. In the present study, we hypothesized whether inflammatory reaction in the CNS could be a mediator of HPA axis response to cranial irradiation (CI). Therefore, we analyzed time-course changes of serum corticosterone level, as well IL-1 beta and TNF-alpha level in the serum and hypothalamus of juvenile rats after CI. Protein and gene expression of the glucocorticoid receptor (GR) and nuclear factor kappaB (NF kappa B) were examined in the hippocampus within 24 h postirradiation interval. Cranial irradiation led to rapid induction of both GR and NF kappa B mRNA and protein in the hippocampus at 1 h. The increment in NF kappa B protein persisted for 2 h, therefore NF kappa B/GR protein ratio was turned in favor of NF kappa B. Central inflammation was characterized by increased IL-1 beta in the hypothalamus, with maximum levels at 2 and 4 h after irradiation, while both IL-1 beta and TNF-alpha were undetectable in the serum. Enhanced hypothalamic IL-1 beta probably induced the relocation of hippocampal NF kappa B to the nucleus and decreased NF kappa B mRNA at 6 h, indicating promotion of inflammation in the key tissue for HPA axis regulation. Concomitant increase of corticosterone level and enhanced GR nuclear translocation in the hippocampus at 6 h might represent a compensatory mechanism for observed inflammation. Our results indicate that acute radiation response is characterized by increased central inflammation and concomitant HPA axis activation, most likely having a role in protection of the organism from overwhelming inflammatory reaction.Ministry of Education and Science of the Republic of Serbia [173044