MARKET OF ORAL ANTIDIABETIC DRUGS IN THE REPUBLIC OF CRIMEA

Diabetes mellitus is one of the most significant social problems of public health. The main pathogenetic factors in the development of type 2 diabetes mellitus are a decrease in insulin synthesis by β­cells of Langerhans islets or impaired insulin receptor sensitivity to insulin, which leads to a high risk of insulin resistance and β­cell dysfunction.

Transgenerational evidence of increases in dopamine D2 receptor sensitivity in rodents: Impact on sensorimotor gating, the behavioral response to nicotine and BDNF

Background/Aims: Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 (DAD2) receptor sensitivity in adult animals. We investigated if increased DAD2 sensitivity would be passed to the next (F1) generation, and if these animals demonstrated sensorimotor gating deficits and enhanced behavioral responses to nicotine. Methods: Male and female rats were intraperitoneal (IP) administered quinpirole (1 mg/kg) or saline (NS) from postnatal day (P)1–21. Animals were either behaviorally tested (F0) or raised to P60 and mated, creating F1 offspring. Results: Experiment 1 revealed that F1 generation animals that were the offspring of at least one NQ-treated founder increased yawning behavior, a DAD2-mediated behavioral event, in response to acute quinpirole (0.1 mg/kg). F1 generation rats also demonstrated increased striatal β arrestin-2 and decreased phospho-AKT signaling, consistent with increased G-protein independent DAD2 signaling, which was equal to F0 NQ-treated founders, although this was not observed in all groups. RNA-Seq analysis revealed significant gene expression changes in the F1 generation that were offspring of both NQ-treated founders compared to F0 NQ founders and controls, with enrichment in sensitivity to stress hormones and cell signaling pathways. In Experiment 2, all F1 generation offspring demonstrated sensorimotor gating deficits compared to controls, which were equivalent to F0 NQ-treated founders. In Experiment 3, all F1 generation animals demonstrated enhanced nicotine behavioral sensitization and nucleus accumbens (NAcc) brain-derived neurotrophic factor (BDNF) protein. Further, F1 generation rats demonstrated enhanced adolescent nicotine conditioned place preference equivalent to NQ-treated founders conditioned with nicotine. Conclusions: This represents the first demonstration of transgenerational effects of increased DAD2 sensitivity in a rodent model.

Analysis of melatonin concentration and its correlation with ovarian disfunction among obese women of reproductive age

One of the new directions in the study of reproductive disorders in obese women is the effect and receptor sensitivity of melatonin on the gonadotropic function of the pituitary gland and ovariogenesis, taking into account the chronology of «light pollution». At the present stage, there is very little literature on the influence of the aspects of «light pollution» on the problem of obesity and reproductive disorders in the literature. This review is an attempt to combine the above problem in terms of the impact of «light pollution» and the level of receptor sensitivity of melatonin in women of reproductive age with obesity. The literature search was carried out in Russian (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. Free access to the full text of the articles was a priority. The selection of sources was prioritized for the period from 2015 to 2019. However, given the insufficient knowledge of the chosen topic, the choice of sources was dated from 1992. The work was carried out as part of the study «Central and peripheral pathophysiological mechanisms of development of adipose tissue diseases, taking into account clinical and hormonal characteristics» 2020–2022.

Cardiopulmonary and Neurologic Dysfunctions in Fibrodysplasia Ossificans Progressiva

Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare but debilitating disorder characterized by spontaneous, progressive, and irreversible heterotopic ossifications (HO) at extraskeletal sites. FOP is caused by gain-of-function mutations in the Activin receptor Ia/Activin-like kinase 2 gene (Acvr1/Alk2), with increased receptor sensitivity to bone morphogenetic proteins (BMPs) and a neoceptor response to Activin A. There is extensive literature on the skeletal phenotypes in FOP, but a much more limited understanding of non-skeletal manifestations of this disease. Emerging evidence reveals important cardiopulmonary and neurologic dysfunctions in FOP including thoracic insufficiency syndrome, pulmonary hypertension, conduction abnormalities, neuropathic pain, and demyelination of the central nervous system (CNS). Here, we review the recent research and discuss unanswered questions regarding the cardiopulmonary and neurologic phenotypes in FOP.

Targeting insulin resistance with selected antidiabetic agents prevents menopausal associated central obesity, dysglycemia, and cardiometabolic risk

Menopause consequent to reduced circulating estrogen is associated with diminished insulin receptor sensitivity and fat redistribution, particularly central adiposity and increased waist circumference. Peri and menopausal women are at risk of hyperglycemia, prediabetes and attendant metabolic disturbances. Hormone replacement therapy increases insulin receptor sensitivity, but may precipitate an increased cardiovascular risk, depending on the route, if not commenced within the proposed period denoted by the ‘timing hypothesis’. The therapeutic ideal of dietary modification with increased physical activity may have compliance issues. We theorize that selected antidiabetic agents reduce visceral fat deposits, restore insulin sensitivity and inhibit inflammatory mediator release. Glucagon-like peptide 1 agonists, sodium-glucose cotransporter 2 inhibitors and even metformin are worthy interventions to treat menopausal-induced obesogenic metabolic conditions. Loss of visceral fat restores insulin receptor sensitivity, decreases central obesity and adipokines to halt dysmetabolic changes.

Pranayama, a simple counterattack on obesity, via its impact on the serum leptin levels

Overweight (i.e. BMI of 25- 29.9) and Obesity (BMI ?30) continues to be one of the neglected global health problems. Leptin is one of the chief adipokines in the body that is basically involved in maintaining a balanced appetite in association with the various other adipokines like the adiponectin, ghrelin etc., Pranayama is the simplest and the ancient, dateless, venerable, non- pharmacological intervention that could be potentially used to maintain a healthy life. To determine how the regular practice of pranayama could significantly alter the deranged serum leptin levels in the obese. The correlative study was carried out in Sree Balaji Medical College & Hospital. The subjects included were 60 obese student volunteers of 17-19 years with no other known complications. We measured their serum leptin levels using ELISA method in the central laboratory, both before and after the pranayama training for 6 months. After 6 months of regular pranayama practice, there was a significant decrease in both their serum leptin levels and their BMI as well. Thus, it was concluded that we can potentially turn off our fat switch by beneficially reducing the serum leptin levels and enhancing the leptin receptor sensitivity in the obese with the regular practice of pranayama.

Impaired light adaptation of ON-sustained ganglion cells in early diabetes is attributable to diminished dopamine D4 receptor sensitivity

Purpose: It has been known for some time that normal retinal signaling is disrupted early on in diabetes, before the onset of the vascular pathologies associated with diabetic retinopathy. There is growing evidence that levels of retinal dopamine, a neuromodulator that mediates light adaptation, may also be reduced in early diabetes. Previously, we have shown that after six weeks of diabetes in a mouse model, light adaptation is impaired at the level of ON-sustained (ON-s) ganglion cells. The purpose of this study was to determine whether changes in dopamine receptor sensitivity contribute to this dysfunction. Here we used single cell retinal patch-clamp recordings from the mouse retina to determine how activating dopamine type D4 receptors (D4Rs) changes the light-evoked and spontaneous excitatory inputs to ON-s ganglion cells, in both control and diabetic animals. We also used in-situ fluorescent hybridization to assess whether D4R expression was impacted by diabetes. We found that D4R activation had a smaller impact on light-evoked excitatory inputs to ON-s ganglion cells in diabetic retinas compared to controls. This impaired D4R signaling is not attributable to a decline in D4R expression, as we found increased D4R mRNA density in the outer plexiform layer in diabetic retinas. This suggests that the cellular machinery of dopaminergic signaling is itself disrupted in early diabetes and may be amenable to chronic dopamine supplementation therapy.