Endothelin Level in Menopausal Women with Comorbidity of the Acute Phase Middle Severity COVID-19 with Arterial Hypertension and Type 2 Diabetes Mellitus.

The levels of endothelins were assessed in menopausal women with arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) in the acute phase of the moderate COVID-19. Women under observation (age 45-69 years) were divided into two groups. Control group consisted of women (n=16) who did not have COVID-19, were not vaccinated, and had no antibodies to SARS-CoV-2 (IgG). The main group included women (n=63) in the acute phase of the moderate COVID-19 accompanied by pneumonia. According to the clinical and anamnestic data analysis, the main group was divided into subgroups: without AH and T2DM (n=21); with AH and without T2DM (n=32); and with AH and T2DM (n=10). The parameters of clinical blood analysis, as well as endothelin-1, endothelin-2, and endothelin-3 levels were assessed. In women with a moderate COVID-19, the endothelin-1 and endothelin-2 levels were increased compared to the control regardless of AH and T2DM status. We found no statistically significant differences in the studied parameters of endothelial dysfunction between the subgroups of menopausal women in the acute phase of the moderate COVID-19.

Alpha Diversity Indices as Indicators of the Variability of Gut Microbiota in Obese Adolescents of Different Ethnicities.

We compared alpha diversity indices of the intestinal microbiota in adolescents with obesity and normal body weight, taking into account their ethnicity. Intestinal biocenosis was studied by metasequencing of amplicon libraries of V3-V4 fragments of the 16S rRNA gene. The alpha diversity of the microbiota was assessed using classical and alternative indices. Statistically significant differences in intestinal microbiota were observed between Russians with obesity and Buryats with normal body weight, as well as between Russians with obesity and Buryats with obesity when assessing the Shannon-Weaver, Chao1 indices, Faith phylogenetic diversity index, ACE, Fisher, Gini coefficient, Margalef, and Menkhinik indices. It was shown that alpha diversity indices can be used to assess significance of differences and variability of the intestinal microbiota in multifactorial diseases such as obesity in adolescents; however, the scope of application of the criteria should be considered.

The Level of Sex Hormones and Corticosterone in Female Rats during Modeling of Visceral Obesity, Subsequent Physical Activity, and Normalization of the Diet.

The effects of diet-induced visceral obesity and non-drug options of its correction on the level of sex hormones and corticosterone were evaluated in 84 female Wistar rats. During stage I, the rats received either a standard diet (STD) or a high-calorie diet (HCD) for 8 weeks. During stage II, the animals were divided into subgroups depending on obesity correction: without correction (STD control and HCD), transition from HCD to STD (HCD/STD) and/or physical activity (treadmill exercise) for the next 8 weeks (HCD/STD+exercise, STD+exercise, and HCD+exercise). Diet-induced visceral obesity resulted in hyperandrogenization and increased blood corticosterone levels in females. Transition from HCD to STD regardless of physical activity led to normalization of testosterone level and, accordingly, to return to the functional norm of estrogen-androgen balance. The positive effect of moderate physical activity on hormonal status is realized only against the background of a balanced diet or during the transition from HCD to STD.

Oxidative Damage of DNA, Proteins and C-Reactive Protein Parameters in Girls and Boys with Exogenous Constitutional Obesity.

The parameters of oxidative damage of DNA, proteins, as well as the parameters of the thiol-disulfide system and C-reactive protein in adolescent girls and boys with exogenous constitutional obesity (ECO) were evaluated. In girls and boys with obesity, the levels of 8-hydroxy-2'-deoxyguanosine (marker of DNA destruction) were higher than in controls. Evaluation of the activity of the thiol-disulfide system revealed increased levels of oxidized glutathione (GSSG) and decreased levels of the reduced glutathione (GSH) and GSSG ratio (GSH/GSSG) in adolescents with ECO regardless of the sex in comparison with the control. C-reactive protein was also higher in the ECO groups regardless of the sex. The levels of glutathione peroxidase in obese boys were higher than in girls. In view of the revealed shifts, corrective measures with the prescription of drugs with antioxidant properties are recommended in adolescents with ECO to stabilize the indices.

[Neuroendocrine changes among 45-60 years old women with COVID-19 and 12 months after the disease.]

Climacteric women have the post-COVID period clinical features, which can lead to an acceleration of the aging. The study consists in assessing individual parameters of the neuroendocrine system in climacteric women with a moderate course of COVID-19 and 12 months after the disease. Under observation were women aged 45-69 years, who were divided into groups: women who did not have COVID-19, not vaccinated, with no antibodies to COVID-19 (IgG) - control group (n=16); women in the acute phase of COVID-19 with a moderate course, accompanied by pneumonia - main group (n=63); patients from the main group who agreed to be examined 12 months after COVID-19 (n=15). The prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, cortisol, testosterone, 17-OH-progesterone, dihydroepiandrosterone sulfate (DHEA-S) levels were assessed. In women with COVID-19 compared with the control the prolactin level was increased (p=0,0002) and the estradiol (р=0,032), testosterone (p=0,004), cortisol (p=0,009), 17-OH-progesterone (p=0,025) and DHEA-S (p=0,003) levels were reduced. Intragroup comparison of hormones showed a decrease in the prolactin level (р=0,041) and increase in the 17-OH-progesterone (р=0,011) and DHEA-S (р=0,0006) levels 12 months after the disease. With a personalized consideration of this group a decrease in the prolactin level is observed in 73,3% of these patients. In the same period, there was an increase in testosterone levels in 46,7% of women, cortisol - in 73,3% of women, 17-OH-progesterone - in 80% of women, DHEA-S - in 100% of cases. When comparing these hormonal parameters between the group of patients who recovered from COVID-19 12 months ago and the control, no statistically significant differences were found, however, patients were identified in whom prolactin and cortisol exceeded the reference values, although in the acute phase of COVID-19 the values of these indicators corresponded to the reference values.

Blood Cytokines of the Ovarian Vein Basin in Different Stages of Pelvic Varicose Veins.

We analyzed the blood concentration of pro- and anti-inflammatory cytokines in the ovarian vein basin area in women of the reproductive age with primary pelvic varices. Increase in the disease severity was accompanied by a significant increase in proinflammatory cytokines (TNFα, IL-1ß, IL-2, IL-6, and IL-8) and the proinflammatory index (IL-6/IL-10), whereas anti-inflammatory cytokine production changed ambiguously (increase of IL-4 at stage I, decrease of IL-10 at stage II, significant decrease of IL-4 and IL-10 at stage III). Control of these changes in female patients should probably be an important component of treatment measures and prevention of morphofunctional disorders occurring at disease progression, in particular at stage III of the disease.

Length of Leukocyte Telomeres in Newborns of HIV-Infected Mothers.

We studied the relative length of telomeres in newborns with unrealized perinatal transmission of HIV (zero viral load according to PCR results). A cross-sectional survey of 62 newborns of HIV-infected mothers (Apgar score 8); the control group consisted of 80 healthy newborns (Apgar score 8). DNA extracted from whole venous blood samples was analyzed. In newborns of HIV-infected mothers, the relative length of telomeres was significantly lower (0.69 (0.66; 0.72)) than in newborns of the control group (1.1 (0.97; 1.22)) (p<0.001). No significant differences in the relative length of telomeres were found between newborns of mothers with a viral load at the time of delivery and with undetectable viral load: 0.69 (0.66; 0.73) and 0.69 (0.63; 0.72). These findings indicate that HIV-infection in mothers or exposure to antiretroviral therapy has an impact on the relative telomere length in leukocytes of newborns.

Oxidative Stress Reactions in Women of Reproductive Age with Metabolic Syndrome.

We analyzed the levels of LPO products and antioxidant defense components in women with the metabolic syndrome. Women with the metabolic syndrome had higher values of substrates with unsaturated double bonds and final TBA-reactive substances in comparison with the control group and higher levels of unsaturated double bonds, primary and end products of LPO, and retinol in comparison with the reference group (women with less than 3 signs of metabolic syndrome). No statistically significant differences between the groups were revealed while estimating the coefficient of oxidative stress; however, there was a tendency to an increase in the median value of this parameter in the group with metabolic syndrome. Thus, the results of the study indicate the activity of LPO reactions at different stages in women of reproductive age with the metabolic syndrome, which points to the necessity to evaluate and monitor the content of these metabolites in the patients of this cohort for the purpose of prevention and treatment.

Features of the Free Radical Oxidation Process and Antioxidant System in Newborns Born to HIV-Infected of Mothers Who Received Antiretroviral Therapies to Prevent HIV Transmission.

The LPO processes and the state of the antioxidant system in perinatally HIV-exposed newborns were studied. Perinatally HIV-exposed (n=62) and healthy newborns (n=80; control) were examined retrospectively (Apgar score 8 in both groups). Blood plasma and erythrocyte hemolysate were used as the material for biochemical tests. Using spectrophotometric, fluorometric, and statistical methods, we found enhanced LPO processes insufficiently compensated by the antioxidant system with excessive accumulation of damaging metabolites in the blood of perinatally HIV-exposed newborns. These changes can be a consequence of oxidative stress during the perinatal period.

Pro-and Antioxidant Status in Newborn with COVID-19.

There is practically no information on the state of oxidative stress reactions in newborns with coronavirus infections. At the same time, such studies are extremely important and can contribute to better understanding of the process of reactivity in patients of different ages. The content of pro- and antioxidant status indicators was assessed in 44 newborns with confirmed COVID-19. It was found that the content of compounds with unsaturated double bonds, primary, secondary, and final LPO products were elevated in newborns with COVID-19. These changes were accompanied by higher SOD activity and retinol level and reduced activity of glutathione peroxidase. Contrary to popular opinion, newborns can be a COVID-19-susceptible age group and require more close monitoring of metabolic reactions during the period of neonatal adaptation that is an aggravating background during infection.

Differences in Gut Microbiota Composition and Predicted Metabolic Functions: a Pilot Study of Adolescents with Normal Weight and Obesity.

Understanding the principles underlying the stability and sustainability of the gut microbiome of adolescents with normal weight and obesity will make it possible to implement a personalized approach to the correction of metabolic disorders. The article presents the results of a pilot study of the diversity and metabolic potential of the gut microbiome in adolescents with normal body weight and obesity. Biological material was studied using metagenomic sequencing of the V3-V4 variable regions of the 16S rRNA gene. In all adolescents with normal weight, similar degree of the phylogenetic relationship between the bacterial taxa of the community was demonstrated. In contrast, obese adolescents were characterized by the presence of phylogenetically distinct taxa in the gut microbiota. However, even with differences in taxonomic composition, the gut microbial community can compensate for the absence of certain taxonomic groups by implementing the necessary metabolic functions using other phylogenetically close taxa.

Biochemical Status of Obese Male Adolescents of Different Ethnicity: Discriminant Analysis in the Identification of the Most Informative Indicators.

Parameters of the lipid metabolism and lipid peroxidation-antioxidant defense system in male adolescents with obesity, representatives of European and Mongoloid ethnicity were evaluated. Discriminant analysis revealed the most informative biochemical parameters for obese male adolescents: glutathione-S-transferase, VLDL cholesterol, glutathione peroxidase, reduced glutathione, and SOD activity for obese male Caucasian adolescents and glutathione-S-transferase, VLDL cholesterol, α-tocopherol, and glutathione peroxidase for Mongoloids obese male adolescents. The use of discriminant analysis allows implementing a differentiated ethnicity-oriented approach to prescribing antioxidant drugs in the complex therapy of obesity.

Superoxide Dismutase Activity in Male and Female Patients of Different Age with Moderate COVID-19.

The study involved 271 patients (132 men and 139 women) with moderate COVID-19. Superoxide dismutase (SOD) activity in erythrocytes was measured spectrophotometrically. In total group of patients (divided into age groups of 18-35, 36-45, 46-60, and 61-90 years), higher SOD activity was found in the 18-35 age group in comparison with the groups 46-60 years (p<0.01) and 61-90 years (p<0.05). Then, the groups were additionally divided by sex. In men, no differences in enzyme activity were found between the age groups. In women of early reproductive age, SOD activity was higher than in groups 36-45, 46-60, and 61-90 years. The sex differences consisted in higher SOD activity in women aged 18-35 years in comparison with men of this age. These data should be taken into account when choosing the tactics of therapy for patients with moderate COVID-19 course.

Content of Carbonyl Compounds and Parameters of Glutathione Metabolism in Men with Type 1 Diabetes Mellitus at Preclinical Stages of Diabetic Nephropathy.

The content of carbonyl compounds (methylglyoxal and TBA-reactive substances) and components of the glutathione system (activities of glutathione-dependent enzymes, content of oxidized and reduced glutathione) and their interrelationships were studied in men of young reproductive age with type 1 diabetes mellitus at the stages of normo- and microalbuminuria. In patients with normoalbuminuria, the level of methylglyoxal, reduced and oxidized glutathione, and glutathione reductase activity were increased and the content of TBA-reactive substances was decreased. In the group with microalbuminuria, an increase in content of methylglyoxal and activity of glutathione-dependent enzymes relative to the control values were observed; the content of TBA-reactive substances was increased and glutathione reductase activity was decreased relative to the group with normoalbuminuria. In patients with microalbuminuria, a strong correlation between the mean glomerular filtration rate and the blood level of methylglyoxal was revealed.

Oxidative Stress: Pathogenetic Role in Diabetes Mellitus and Its Complications and Therapeutic Approaches to Correction.

The review presents modern views about the role of oxidative stress reactions in the pathogenesis of types 1 and 2 diabetes mellitus and their complications based on the analysis of experimental and clinical studies. The sources of increased ROS generation in diabetes are specified, including the main pathways of altered glucose metabolism, oxidative damage to pancreatic ß-cells, and endothelial dysfunction. The relationship between oxidative stress, carbonyl stress, and inflammation is described. The significance of oxidative stress reactions associated with hyperglycemia is considered in the context of the "metabolic memory" phenomenon. The results of our studies demonstrated significant ethnic and age-related variability of the LPO-antioxidant defense system parameters in patients with diabetes mellitus, which should be considered during complex therapy of the disease. Numerous studies of the effectiveness of antioxidants in diabetes mellitus of both types convincingly proved that antioxidants should be a part of the therapeutic process. Modern therapeutic strategies in the treatment of diabetes mellitus are aimed at developing new methods of personalized antioxidant therapy, including ROS sources targeting combined with new ways of antioxidant delivery.

Evaluation of the Protective Effect of Ademetionine, Cytoflavin, and Dihydroquercetetine on Blood Enzymes Activity in Rats Treated with High Doses of Sodium Valproate.

We evaluated the protective effect of ademetionine, cytoflavin, and dihydroquercetin on activity of serum enzymes in rats treated with high doses of sodium valproate for 28 days. Ademetionine and cytoflavin produced the greatest protective effect, the effect of dihydroquercetin was less pronounced. In rats treated with ademetionine, AST activity decreased as soon as on day 7 and remained at this level until the end of the experiment; ALT, alkaline phosphatase, and γ-glutamyl transferase activities decreased on days 21 and 28 of the study. Cytoflavin produced similar effects, the effect of dihydroquercetin was observed on days 21 and 28 for AST, ALT, alkaline phosphatase and on day 28 for γ-glutamyl transferase. These results substantiate the use of hepatoprotective drugs in case of long-term treatment with anticonvulsants in patients with epilepsy.

Analysis of neutrophils functional activity in men with mechanical jaundice of various genesis.

Obstructive jaundice (OJ) or blockage of the bile duct code K83.1 (according to ICD 10), occurs in approximately 45-50% of cases of all varieties of jaundice, it can be both non-tumor and tumor genesis. The functional pathway plays a special role in the genesis of complications of breast the activity of neutrophils as key effector cells responsible for the development of the inflammatory process in the breast. Investigation of the metabolic mechanisms of the functioning of neutrophils allows us to identify intracellular targets, when exposed to It was possible to modulate the level of cell reactivity.The study used data from 47 men with obstructive jaundice of non-tumor origin and 45 men with obstructive jaundice of tumor origin (stage I-II of the tumor process). As a control, data from 100 practically healthy men were used. A pronounced change in the kinetics of the chemiluminescent response of neutrophils in men with obstructive jaundice was found, consisting in an increase in the time to reach the maximum intensity, maximum intensity, area under the curve and activation index for both spontaneous and luminol-dependent induced chemiluminescence. The development of the tumor process in this category of patients was accompanied by a decrease in the area parameter under the curve during spontaneous and induced reactions, time to maximum, intensity maximum and activation index during spontaneous chemiluminescence. The data obtained indicate a marked increase in the values of the functional activity of neutrophils in patients with obstructive jaundice of benign origin, as well as a sharp decrease in their values in the presence of a pathological process of malignant origin.

Activity of Antioxidant Enzymes in the Regional Blood Flow during Pelvic Venous Disorders in Women.

Activity of some antioxidant enzymes (superoxide dismutase, catalase, and glutathionedependent enzymes), as well as the level of LPO products in the region regional blood flow (collateral branches of the main trunks of ovarian veins) in women with pelvic venous disorders were studied. A compensatory increase in activity of superoxide dismutase, catalase, and glutathione peroxidase during stage I of the disease was found; during stage II, superoxide dismutase activity decreased and glutathione peroxidase increased, while during stage III, pronounced decrease in activities of all studied enzymes was observed. The level of lipid peroxidation products in the regional blood flow increased as the disease progressed, with maximum values in the third stage.

Morphofunctional State of the Periodontal Tissues in Humans and Rats with Arterial Hypertension.

We performed comparative analysis of hemodynamic in the periodontal microcirculatory bed in adolescents with arterial hypertension (AH) and morphological changes in the periodontal tissues of in hypertensive ISIAH rats of comparable biological age. In the periodontal tissues of adolescents with hypertension, the blood flow velocity and index of peripheral resistance increased, while pulse pressure decreased. In ISIAH rats, the mean area of periodontal and pulp vessels increased and the area of the connective tissue decreased. These results can be used in the complex assessment of morphofunctional state periodontium during hypertension development.

[The relationship of hemodynamic parameters of periodontal microvascular bed and lipid peroxidation products in adolescents with arterial hypertension]. / Vzaimosvyaz' pokazatelei gemodinamiki mikrososudistogo rusla parodonta i produktov lipoperoksidatsii u podrostkov s arterial'noi gipertenziei.

THE AIM: Of the study was to establish the relationship of hemodynamic parameters of periodontal tissues and lipid peroxidation products in adolescents with arterial hypertension (AH). METHODS: The study included 132 adolescents (average age 14.51±1.91 years), from which 2 clinical groups (1 - the group with AH without periodontal disease (n=19, average age - 15±1.53 years) and 2 - the group with AH with periodontal diseases (n=57, average age - 14.7±1.89 years)) and 2 comparison groups (3 - the comparison group without AH and periodontal diseases (n=19, average age - 13.82±1.89 years) and 4 - comparison group without AH and with periodontal diseases (n=37, mean age - 14.57±2.01 years)) were formed. Hemodynamic analysis of the periodontal microcirculatory bed using the Doppler ultrasound method and the level of lipid peroxidation products using spectrophotometric and fluorometric methods was performed. RESULTS: In adolescents with hypertension without and with inflammatory periodontal diseases as a whole, unidirectional changes in the hemodynamics of the vascular bed of the periodontium were observed in the form of increased values of the maximum blood flow velocity in systole and an increase in the peripheral resistance index. At the same time, the group with hypertension and periodontal disease was distinguished by lower values of these indicators. In the system of lipid peroxidation, increased values of ketodienes and conjugated trienes occurred in patients with hypertension without periodontal disease and end products that actively reacting with thiobarbituric acid in patients with hypertension and periodontal disease. Correlation analysis showed the presence of intersystem relationships between the hemodynamic parameters of the vascular bed of periodontal adolescents with hypertension without periodontal disease. In the group of adolescents with arterial hypertension and periodontal disease, there was a decrease in the correlation coefficients between intersystem parameters by almost two times, as well as the appearance of pathological dependencies between toxic metabolites of the lipid peroxidation process - products that actively reacting with thiobarbituric acid and vascular blood flow indicators. CONCLUSION: It has been noted that in adolescent patients with hypertension and periodontal diseases on the background of lower vascular blood flow and accumulation of end toxic metabolites, pathological dependencies occur between them, which may contribute to more intense damage to the tissues of the periodontal complex in the presence of hypertension.