Vol 7, No 9 (2021)

The widespread prevalence of high-calorie nutrition in countries with a high living standard in combination with a decrease in muscle energy expenditure leads to the formation of insulin resistance mechanism in the genetic memory and metabolic syndrome (MS) development. The aim of the research is to study the influence of gene polymorphisms at metabolic disorders develooment among young inhabitants of the North. Material and methods. A prospective cohort study of 883 young people living in conditions equivalent to the Far North conditions for a long time (average duration of residence - 27,9±0,005 years) for the period 2015-2020 was performed. 749 patients had MS and 134 were without MS manifestations. Within the framework of the performed molecular genetic study, the following gene polymorphisms were studied: rs1378942 of the CSK gene, rs1801133 (C677T) of the MTHFR gene, lTGA2B gene, rs7903146 of the TCF7L2 gene, rs1799752 of the ACE gene. Genomic DNA was isolated from venous blood by phenol-chloroform extraction methodic. Gene polymorphism was tested by means of polymerase chain reaction with polymorphism of restriction fragments' lengths. Results. While assessing anthropometric data and laboratory test results, patients with MS revealed hyperglycemia in 31,8%, hyperinsulinemia - in 13,8%, HDL hypocholesterolemia - in 19.4%, hypertriglyceridemia - in 78,1%, arterial hypertension - in 14,1% of cases. In the total sample of examined individuals, among the studied polymorphic loci, the loci of the ACE and CSK genes were 29 more common. When analyzing the distribution of genotype pairs among the examined MS patients in the general cohort, the most common were combinations of polymorphism of the ITGA2B gene and the polymorphic locus rs1378942 of the CSK gene (18,0%). At the same time, these type of correlations were find more often among the indigenous (18,9%) and non-indigenous rural (18,6%) residents of the North. In case of combination of MS components, were most often detected polymorphisms of genes including heterozygous genotypes ID of the ACE, ITGA2B gene, homozygous CC genotypes of TCF7L2 and MTHFR genes, and heterozygous GT genotype of the CSK gene. Conclusion. Clinical manifestations of MS in examined non-indigenous and indigenous young inhabitants of the North are caused by complex intergenic interactions of the studied single nucleotide polymorphisms of five genes: ACE, TCF7L2, ITGA2B, CSK, MTHFR. Combinations of mutant gene polymorphisms were found more common - heterozygous genotypes ID of the ACE, ITGA2B gene, homozygous CC genotypes of TCF7L2 and MTHFR genes, heterozygous GT genotype of CSK gene. Among them, the CSK gene plays a predominant role in MS development. Early identification of genetic predictors of metabolic disorders is of great clinical importance for timely prevention of cardiovascular diseases and diabetes mellitus development.

Genetic factors play an important role in the development of various diseases of the gastrointestinal tract, including gastroesophageal reflux disease (GERD). Aim of the research was to study the prevalence of genetic polymorphism of the GNBB3 825C/Tgene in patients with GERD living in the Trans-Baikal Territory, depending on the clinical picture of the disease and the nature of refluxate. Material and methods. The study involved 139 people who identify themselves as Caucasians and have lived in the Trans-Baikal Territory for at least three generations time. The first group included 79 patients with GERD (30 male and 49 female patients, median age was 43 (33; 57) years), the second (control) group included 60 people (28 males and 32 females, median age - 44 (37; 54) years). Genotyping of the C825T polymorphic locus of the G-protein beta subunit (GNBB3) was performed by PCR methodic. Methods of nonparametric statistics were used, the differences were considered significant at p <0,05. Results. Both groups revealed the presence of three genotypes GNBB3 C825T (C/C, T/T, C/T). There were no differences in the prevalence of genotypes and alleles between patients with GERD and the control group. Patients who experience belching 1 or more times a week are more likely to have the GNBB3 825C/T genotype (OR=3,235; 95% CI: 0,838-12,488; p=0,052), while the prevalence of the T allele in these patients did not differ. In patients with heartburn occurring at least 1 time per week, there was a tendency towards the most frequent spread of this genotype (p=0,066). Conclusion. The prevalence of 825 C / T GNBB3 genotypes was comparable in patients with GERD and in the control group. The CNBB3 825 C / T genotype is associated with GERD with clinical manifestations of the disease at least 1 time per week.

Numerous studies indicate that BDNF may play an important role in energy homeostasis, in the regulation of food intake, and in the peripheral regulation of metabolism. The aim of the research was to search for the correlation between single nucleotide polymorphism c.189G> A p. (Val66Met) of the BDNF gene and the levels of circulating in blood leptin in Yakut population. Material and methods. Study sample consisted of 281 persons (186 females and 95 males), the average age of the participants was 19,8±1,5 years. The sample was stratified by sex and subdivided according to body mass index (BMI) into three groups: underweight (n=37), normal weight (n=215), and overweight/obesity (n=29) group. Results. In the Yakut population, the frequency of the major allele p. (Val66) was 84,9%, the minor allele p. (Met66) - 15,1%. Due to the low frequency of distribution of homozygotes p. [Met66]; [Met66] and heterozygote p. [Val66]; [Met66], in the analysis, these two genotypes were combined into one group p. [Val66]; [Met66] + p. [Met66]; [Met66]. As a result, an association of the genotypes of p. [Val66]; [Met66] + p. [Met66]; [Met66] with decreased serum leptin levels in normal weight females (p=0,01). In males with normal weight, there was a tendency towards a decrease in leptin level in carriers of the genotypes p. [Val66]; [Met66] + p. [Met66]; [Met66] (3,83±0,85 ng/ml) comparatively with homozygotes p. [Val66]; [Val66] (5,58±0,93 ng/ml; p=0,09). Conclusion. Our results indicate that individuals with p. (Met66) allele probably may have an impaired signaling pathway of leptin through BDNF in the ventromedial hypothalamic nucleus. According to this assumption, carriers of the p. (Met66) allele may have a decreased appetite since their birth time, which leads to a decrease in the amount of consumed foos and an increase in the use of fats in energy metabolism. This, in turn, reduces the accumulation of normal amounts of adipose tissue required for leptin production and is a risk factor for the development of eating disorders associated with anorexia nervosa and bulimia nervosa.

The ambiguity of data on Nrf2-mediated redox-sensitive signaling pathways participation in atherogenesis and the progression of atherosclerosis determines the need to search for new data on the mechanisms of cause-effect relationships of these processes. The aim of the research was to study the features of clinical and laboratory markers of atherosclerosis and the level of genes expression of the antioxidant defense system (NRF2, HMOX1, NQO1, GSTP1) in correlation to the echoscopically verified degree of carotid artery (CA) stenosis. Material and methods. The study included 160 patients from the clinic of the Federal research center for fundamental and translational Medicine aged from 35 to 78 years. They underwent clinical and laboratory diagnostics, ultrasound examination of brachiocephalic arteries, assessment of the expression of genes involved in the formation of antioxidant protection (NRF2, NQO1, HMOX1, GSTP1) using RT-PCR methodic. Results. It was found that in peripheral blood leukocytes of patients with verified CA atherosclerosis, the expression of GSTP1, NQO1, and NRF2 genes is reduced (by 49, 51, and 44%, respectively), while the mRNA contained amount of the HMOX1 gene is not changed. A correlation was revealed between the severity of expression of genes GSTP1, HMOX1, NQO1, NRF2, indicators 77 of blood lipid spectrum, as well as the degree of CA stenosis: an inverse correlation between the expression of NQO1 gene and the percentage of stenosis in the left common CA, expression of GSTP1 gene and the atherogenic coefficient, a direct relationship between the level of mRNA of the NRF2 gene and the concentration of high density lipoproteins (HDL). A direct correlation was found between the concentration of triglycerides and the thickness of the «intima-media» complex, the content of total cholesterol and the blood flow rate in the right internal CA, an inverse correlation between the level of HDL, as well as the concentration of apolipoprotein A and the thickness of the «intima-media» complex of the common CA. Conclusion. Complex pathogenetic interrelationships of the expression of antioxidant defense genes, the degree of atherosclerotic stenosis and blood flow velocity of CA, as well as indexes of blood lipid spectrum are shown.

He diagnosis and estimation of risk factors for spontaneous pneumomediastinum (SPM) are of particular practical interest since the occurrence of this complication can significantly aggravate the course of COVID-19, while having vague clinical manifestations. Purpose of the study - to determine the main clinical and laboratory characteristics, as well as risk factors for a severe course of the disease in patients with COVID-19 pneumonia, complicated by the development of SPM unrelated to invasive ventilation (IV). Material and methods. The study included 130 patients (73 men and 57 women) with COVID-19 pneumonia who were diagnosed with SPM prior to episodes of invasive mechanical ventilation. The average age of the patients was 61±15,3 years. All patients had COVID-19 pneumonia on chest CT, confirmed by PCR testing. Upon admission to the hospital, demographic data, typical complaints, clinical variables and laboratory parameters were collected. Results. SPM was detected in 130 patients, in 29 cases (22%), in addition to pneumomediastinum, unilateral and bilateral pneumothorax of various sizes developed. The most common comorbidities in the examined patients included: hypertension (71%), overweight and obesity (70%), coronary heart disease (20%), diabetes mellitus (15,4%), chronic obstructive pulmonary disease (9,2 %), cancer (9,2%), bronchial asthma (6,2%). Laboratory indicators of the examined patients had characteristic changes for COVID-19 pneumonia. The values of LDH, CRP, D-dimer and ferritin in blood plasma were increased. SPM was detected in the progression stage, with an increase in the volume of lung lesions before CT 3 (19,3%) and CT 4 (80,6%). The timing of SPM development from the onset of the disease was 13,0±7,3 days. Logistic regression showed that predisposing factors (OR 3,94; 95% CI: 1,13-13,6; p=0,031) and radiological severity (OR 6,63; 95% CI: 1,36-32,3; p=0,019) were independently associated with the risk of pneumomediastinum. Conclusion. SPM in patients with COVID-19 who have not used invasive mechanical ventilation occurs in the progression stage, with an increase in the volume of lung lesions according to CT data to 3 and 4 degrees. The formation of SPM is associated with an increase in the severity of COVID-19 pneumonia, an increase in the frequency of use of invasive mechanical ventilation, and a higher risk of death.

In the modern world, it remains relevant to search for and study new biological markers that can help early diagnosis of cardiovascular diseases, serve as a laboratory tool for assessing the effectiveness of therapy, be a prognostic marker of possible adverse clinical outcomes and a significant criterion for risk stratification. The purpose of this review is to consider resistin as a diagnostic and prognostic marker in cardiovascular pathology based on the analysis of foreign and domestic literature sources from the PubMed, RSCI, MedLine, Google Scholar, Science Direct databases. Many studies have described such functions of resistin as metabolism of glucose and lipids in the blood, modulation of satiety centers in somatotrophic cells of the hypothalamus and pituitary gland, regulation of the central nervous system, synthesis and secretion of various pro-inflammatory cytokines and differentiation of monocytes into macrophages, effect on heart contractility, angiogenesis , smooth muscle cell activity and kidney function. Blood resistin levels in healthy people are in the range of 7-22 ng/ml (average 15 ng/ml). Further work is required to determine the specific resistin receptor, which will subsequently lead to the identification of specific signaling pathways and will help clarify the role of this biological marker in type 2 diabetes mellitus, dyslipidemia, and cardiovascular diseases.

Optimal management of patients with type 2 diabetes mellitus (DM 2) in connection with the appearance of new medicaments and treatment paradigm evolution can significantly improve the prognosis of the disease. However, modern advances in the management of cardiovascular risks in patients with type 2 diabetes are represented in clinical practice still not widely. That comes in some kind of conflict with the colossal need of patients for possible modification of the natural course of diabetes. The purpose of this review is to introduce a modern viewpoint at the problem of type 2 diabetes treatment, taking into account the therapeutic possibilities for different groups of patients. The review includes substantiation and modern stratification of the baseline cardiovascular risk in type 2 diabetes patients, data from clinical studies and analyzes for each specific group of patients, as well as a description of scientific tools for a broader practical interpretation of the results of these studies.

Endogenous intoxication in case of various pathologies of occupational and infectious etiology plays an essential role in the healing process and in estimation the severity of the disease. Specifying of endogenous intoxication indexes by means of biochemical markers use will help to control detoxification processes, including through the inclusion of various specialized foods in the complex therapy of dietary therapeutic and dietary preventive nutrition. Use of alimentary factors in the process of reducing the negative impact of toxic substances of endogenous origin at human organism should be aimed at maintaining and preserving the rhythm of the main homeostatic systems functioning. The aim of this review is to assess the informative content of endogenous intoxication indexes in various pathologies having occupational and infectious etiology.