SERUM LEVEL AND GENE POLYMORPHISM OF INTERLEUKIN-1α, AND EFFICIENCY OF INFERTILITY TREATMENT BY IN VITRO FERTILIZATION

Search for novel prognostic criteria predicting successful in vitro fertilization remains a nonresolved problem at the present time. The aim of our study was to analyse a predictive role of IL-1α as an additional marker of pregnancy after in vitro fertilization (IVF). The study included 120 women with tubo-peritoneal infertility subjected to the IVF procedure. Retrospectively, two groups were formed of this cohort, dependent on efficiency of in vitro fertilization. Group I included 40 women with successful pregnancy whereas group II comprised 80 women with failed pregnancy. IL-1α concentrations in serum were detected by ELISA technique. A polymorphic rs1800587 marker at 5`UTR region has been amplified by PCR followed by Sanger sequencing. We have shown IL-1α hyperproduction in the women from group I. The women with effective IVF outcome exhibited positive correlation between IL-1α and luteinizing hormone, prolactin, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate levels. The women with ineffective in vitro fertilization have detected a negative correlation between IL-1α levels and anti-Muellerian hormone, a positive correlation of IL-1α with 17-hydroxyprogesterone. The women with T allele of the polymorphic rs1800587 marker at 5`UTR region have shown a 2.5-fold higher chance to become pregnant after IVF than the women carrying C allele (95% CI = [1.45-4.35], р = 0.0009). The women with T/T genotype exhibited a positive correlation between IL-1α and estradiol, testosterone; the subjects with heterozygous C/T genotype showed correlation with estradiol, and those harboring C/C genotype exhibited correlation with follicle-stimulating hormone. The revealed changes suggest a potential involvement of IL-1α into regulation of cyclic processes in the ovary including ovulation. Moreover, IL-1α may participate in formation of pro-inflammatory environment for successful blastocyst implantation

Microbial agents as triggers of developing multiple sclerosis

Multiple sclerosis (MS) currently represents a pressing medical and social issue. This is due to the high prevalence of this pathology among neurological diseases preferentially affecting young people and subsequent rapid disability. This disease still remains a mystery for medicine due to its ambiguous etiology, polymorphism of clinical manifestations and unstable course. Despite the marked development of modern instrumental diagnostic methods, pathognomonic signs have not yet been identified for multiple sclerosis allowing to diagnose the disease with high accuracy at early stages. At the moment, we may only say with confidence that MS is a neurodegenerative disease accompanied by rapid demyelination and death of nerve cells. Complex and diverse pathogenetic mechanisms suggest a multifactorial nature of the disease, which develops due to combination of external factors and hereditary predisposition, which causes altered immune tolerance. The polygenic theory of MS is most substantiated, which implies that the genotype of MS patients consists of many genes, each of which contributes to the disease development. More than 100 genes associated with MS have been identified, among which a special place is taken by the HLA system (human leukocyte antigen), which controls the interaction of immunocompetent cells and carries out an immune response. In addition, new candidate genes have been identified that contribute to the development of MS: interleukin 2 and 7 receptors (IL-2R, IL-7R), differentiation cluster 6 (CD6) and 58 (CD58), tumor necrosis factor α, interferon regulatory factor 8 (IRF8), interleukin 12А (IL-12A) and others. However, to uncover genetic predisposition, it is necessary to experience external trigger factors. The activation of demyelinating process is quite often initiated by various infectious agents, among which the most studied are Epstein–Barr virus, John Cunningham virus, acute encephalomyelitis virus, and human endogenous retroviruses. Intestinal microbiota altered by Candida albicans, Staphylococcus aureus, Acinetobacter calcoaceticus, Bacteroides, Proteobacteria and Firmicutes deserved special attention in developing neurodegenerative disorders. Such an imbalance profoundly affects immune and nervous system functioning, taking part in neurogenesis, myelination, activation of cellular and humoral immune responses. Here we review and analyze the latest data accumulated in Russian and foreign literature regarding the study of the MS epidemiological features, as well as microbiological risk factors for disease development

Clinical Signs and Medical History as Predictors of Enalapril-Associated Dry Cough in Cardiovascular Patients

Angiotensin-converting enzyme inhibitors (ACEIs) are among the most prescribed and effective medicinal products for the treatment of several cardiovascular diseases. According to a number of studies, 30% of patients taking ACEIs develop adverse drug reactions (ADRs), and treatment discontinuation is often required as a result. The most common ADR associated with ACEIs is a dry (non-productive) cough. Nevertheless, the clinical signs and medical history predictive of this ADR in cardiovascular patients are still understudied.The aim of the study was to analyse the clinical signs and medical history predictive of cough in patients with cardiovascular conditions treated with enalapril.Materials and methods. The study was carried out in 2019–2022 and enrolled 224 patients with essential hypertension (grades 2 and 3) treated with enalapril at a dose of 10–20 mg/day. The patients were assigned to 2 groups: Group 1 included 113 patients with enalapril-associated cough, while Group 2 (control group) comprised 104 patients without this ADR. At screening, all the patients underwent a general examination and a check of their allergy and medication history. Using the data obtained, the authors analysed the association of the clinical signs and medical history with the ADR of interest (dry cough).Results. In contrast to the control group, the group with ACEI-associated dry cough included more patients with a history of drug-induced toxicoderma (OR=5.639, CI 2.234–14.236, χ2=15.845, and p<0.001) or type 2 diabetes mellitus (OR=3.409, CI 1.461–7.953, χ2=8.7472, and p<0.01), a family history of bronchial asthma (OR=4.141, CI 2.066–8.299, χ2=17.417, and p<0.001), and a close family history of severe allergic reactions (OR=3.714, CI 1.720– 8.018, χ2=12.137, and p<0.001).Conclusions. A family history of allergy increases the probability of dry cough in patients taking ACEIs. In order to improve the safety of ACEI therapy, patients with cardiovascular conditions should be asked more detailed questions about their personal or first-degree family history of allergy

ASSOCIATION OF INTERLEUKIN-1α GENE POLYMORPHISM (ENCODED REGION rs1800587 5`UTR) WITH EFFICIENCY OF IN VITRO FERTILIZATION

Due to quite low efficiency and high costs of in vitro fertilization protocols, there is a necessity for development of new diagnostic criteria for selection of patients. The purpose of this study was complex analysis of association of polymorphic variants of IL-1α gene (rs1800587 5`UTR region) and main diagnostic criteria of women with tubo-peritoneal infertility and success rate of in vitro fertilization procedure. We have examined 120 women with tubo-peritoneal infertility who were subjected to the microflare protocol of controlled ovarian hyperstimulation which was followed by embryo transfer. Concentration of IL-1α in blood serum was defined by ELISA method by means of test systems of the "Cytokine LLC" (St. Petersburg, Russian Federation). Polymorphic marker rs1800587 at 5`UTR region was analysed with PCR method followed by the sequencing. We have detected no particular features in distribution of polymorphic IL-1α gene variants in pregnant women. The T/T genotype seems to be a conditionally favorable predictor for pregnancy resulting from in vitro fertilization. It has been shown that the IL-1α content in blood serum of pregnant women was increased as compared to women who did not become pregnant. It was also shown that pregnant women with T/T genotype had higher serum IL-1α levels than women with other genotypes. During transvaginal puncture, we have detected that pregnant women with T/T genotype had more oocytes than women with C/C genotype. We have not found significant differences in 17-oxyprogesterone, estradiol, follicle-stimulating hormone, testosterone contents for groups of women with different IL-1α genotypes. As based on this study, the IL-1a involvement in the implantation become more evident. Further studies are required concerning influence of IL-1a on folliculogenesis, ovulation, implantation, decidualization and placenta formation