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.

[Glutathione unit of the antioxidant system activity in pregnant women depending on the sleep quality]. / Aktivnost' glutationovogo zvena antioksidantnoi sistemy u beremennykh v zavisimosti ot kachestva sna.

OBJECTIVE: To assess the enzymatic and non-enzymatic links of the glutathione system in pregnant women depending on the sleep quality. MATERIAL AND METHODS: The study included 64 pregnant women aged 18 to 40 years. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). The results of the clinical and anamnestic examination made it possible to divide the subjects into the control group (PSQI≤5, n=31, mean age 32±5.2 years, body mass index (BMI) 30.86±8.41 kg/m2) and the main group (PSQI>5, n=33, mean age 33±5.23 years, BMI 30.88±7.47 kg/m2). The distribution of women by trimesters between the groups was statistically comparable: I (48.4%), II (32.3%), III (19.3%) in the control group and 1 (48.5%), 2 (36.4%), 3 (15.1%) in the main group. Glutathione status was determined by the content of reduced, oxidized glutathione and their ratio, glutathione peroxidase and glutathione reductase activities. The content of lipid peroxidation products was determined by the levels of diene conjugates and TBA-active products. RESULTS: PSQI was 3.81±1.30 points in the control and 8.88±3.12 points in the main group (p<0.001). There was an increase in the glutathione peroxidase activity (1349 [790.3; 2006] U/l, p=0.016) and oxidized glutathione level (2.17 [1.85; 2.33] mmol/l, p=0.048) in the main group compared with the control group (560 [438.1; 1462] U/l and 1.85 [1.53; 2.25] mmol/l, respectively). There were no statistically significant differences between the groups in the content of lipid peroxidation products such as diene conjugates and TBA-active products. CONCLUSION: The decrease of sleep quality in pregnant women is accompanied by changes in the glutathione component of antioxidant protection activation, which indicates the need to take measures to improve the sleep quality and correct the antioxidant status in these women.

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.

[Prescription of psychotropic drugs off label]. / Naznachenie psikhotropnykh preparatov vne zaregistrirovannykh pokazanii.

The review was written based on the analysis of available publications (Pubmed, other Internet resources) on the problem of off-label use of drugs. It reveals the concept of off-label prescribing and discusses modern approaches to the use of off-label drugs in domestic psychiatric and addiction practice. The problems of normative substantiation of prescribing off-label drugs are discussed. It has been established that, despite some progress in this matter, for patients in adult psychiatric practice, the use of off-label therapy is carried out only by decision of the medical commission. The issue of substantiating the prescription of off-label drugs on the basis of scientific and clinical studies and experience in the use of drugs at the legislative level remains relevant.

[Activity of the telomerase complex before and after CPAP therapy in patients with obstructive sleep apnea syndrome]. / Aktivnost' telomeraznogo kompleksa na fone SIPAP-terapii u patsientov s sindromom obstruktivnogo apnoe sna.

OBJECTIVE: To evaluate changes in the activity of the telomerase complex in patients with obstructive sleep apnea (OSA) before and after continuous positive airway pressure (CPAP) therapy. MATERIAL AND METHODS: In accordance with the objectives of the stages of the study of telomers-telomerase relationships, we maintained the unified design of the study described earlier. The main group 1 (MG1), n=35, consisted of men, aged 53.4 [45.5-60.1] years with characteristic complaints indicating of OSA. The main group 2 (MG2) included the same patients before and after 6 months of CPAP therapy. Blood sampling was performed after the first diagnostic polysomnography (PSG) and after 6 months of CPAP in the morning after the second PSG. The control group (CG) consisted of 26 men, comparable in age and the presence of chronic diseases. Questionnaire, PSG and blood sampling were conducted in CG as well. All participants signed an informed consent. RESULTS: As a result of the STOP-BANG questionnaire conducted before PSG, all patients in the MG1 had scores from 5 to 8. The scores on the Epworth scale were more than 5 points. In the MG2 apnea-hypopnea index decreased from 20.1 to 6.4 ev/hour, the desaturation index decreased from 15.6 to 7.1 ev/hour after 6 months of CPAP. Statistically significant differences in changes in the activity of the telomerase complex were revealed, which after treatment significantly exceed the values of these indicators before treatment. So, telomerase reverse transcriptase value was 0.04 (0.009; 0.06) in the MG1, after treatment it was 0.07 (0.06; 0.09) in the MG2 and 0.134 (0.009; 0.18) in the CG. Telomerase RNA subunit TER1 values were 0.06 (0.03; 0.09), 0.07 (0.05; 0.09) and 0.136 (0.04; 0.17), respectively. However, despite the activation of the telomerase complex during CPAP therapy in patients with OSA, in the CG its activity is significantly higher in comparison with the MG1 and MG2. CONCLUSION: In OSA accompanied by intermittent hypoxia, a decrease in the activity of the telomerase complex was shown. Elimination of nocturnal hypoxia and improvement of breathing during sleep is accompanied by an increase in the activity of the components of the telomerase complex.

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.

Glutathione Component of Antioxidant Status in Menopausal Women with Insomnia.

The study involved 138 women aged 45-60 years in perimenopause (n=55) and postmenopause (n=83) with insomnia (main groups) and without it (control). The levels of reduced (GSH) and oxidized (GSSG) glutathione and glutathione peroxidase activity were determined in erythrocytes; activities of glutathione S-transferase and glutathione reductase were measured in blood serum. The differences with the control groups were found only in perimenopause: higher glutathione reductase activity and reduced GSSG level and GSH/GSSG ratio in women with insomnia (p<0.05). The results of the comparative analysis between the main groups showed lower glutathione reductase activity, increased GSSG level, and a decrease the GSH/GSSG ratio in the postmenopausal period compared with the perimenopause (p<0.05). These results can be used in choosing the tactics for complex therapy of insomnia in menopausal women to correct free radical homeostasis and prevention of oxidative stress.

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.

[Changes in the telomeres length in patients with obstructive sleep apnea after continuous positive airway pressure therapy: a pilot study]. / Izmenenie otnositel'noi dliny telomer u patsientov s sindromom obstruktivnogo apnoe sna na fone SIPAP-terapii: pilotnoe issledovanie.

OBJECTIVE: To evaluate a relative telomere length in patients with obstructive sleep apnea (OSA) before and after a 6-month course of continuous positive airway pressure (CPAP) therapy. MATERIAL AND METHODS: Seventy-five men participated in the study, including 50 men with OSA (the main group 1) and 25 men without OSA (the control group). The average age in the total group was 53.4±3.6 years. Thirty-five men completed the study (the main group 2). According to the design, night polysomnography (PSG) was performed for all the subjects, blood sampling to assess the length of telomeres was carried out in the morning according to the standard method. The values of the relative telomere length were obtained using the difference between the values of the threshold cycles for telomeric DNA and the reference gene albumin (∆CCt). After clarifying the diagnosis, CPAP was applied for 6 months. RESULTS: Statistically significant indicators of PSG were revealed: a decrease in NREM 3 in patients with OSA compared to controls (89.3±15.8 versus 150±23.4 minutes), an increase in NREM1-2 in OSA (296.2±31.1 and 170.1±24.5, respectively), REM was 84.6±15.4 in the main group and 118.5±19.5 in the control group. CPAP therapy conducted for 6 months (at least 4-5 nights a week, lasting at least 5-6 hours of night sleep) demonstrated a significant improvement in the qualitative and quantitative parameters of sleep. In patients of the main group 1, there is a shortening of the telomere length compared with the control group (p<0.001). With the elimination of hypoxia and improvement of the structure of sleep after CPAP, there was an increase in the telomere lengths in the main group 1 from 0.28 [0.24-0.29] to 0.32 [0.30-0.34] in the main group 2 (p=0.03). The telomers length in the control group was 0.53 [0.50-0.55]. CONCLUSION: Intermittent hypoxia and fragmentation of sleep in OSA leads to shortening of telomeres. CPAP, by eliminating the pathophysiological triggers of OSA, contributes to an increase in telomeres lengths and can slow down the premature aging in OSA.

[Age-related menopause and carbonyl stress.]

The review analyzes the literature data on studies of redox homeostasis in women with age-related physiological menopause. Despite the ambiguity of the presented results on the lipids, proteins, carbohydrates oxidative modification, most studies allow us to consider this age period as one of the factors in the carbonyl stress development, which is an integral part of aging. The presence of hyperglycemia and free radical pathology are presented as the main causes of the carbonyl stress development, age-related estrogen deficiency, taking into account their antioxidant properties, is considered as one of the triggers for this condition development, and the glutathione system is identified as one of its main inhibitors.

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.

Glutathione system activity in the blood of overweight postmenopausal women.

One of the important components of the antioxidant defense system is the glutathione system, the activity of which, when overweight, changes direction depending on gender and ethnicity. The results of studies involving overweight menopausal women are mixed. The study involved 61 postmenopausal women, who, after clinical and anamnestic examination, were divided into 2 groups: control (BMI = 19-24.9 kg / m2) and overweight group (BMI = 25-29.9 kg/m2). The use of hormone replacement therapy; the use of antioxidant drugs; diseases of endocrine genesis; exacerbation of chronic diseases; premature early menopause; surgical menopause was the exclusion criteria for women from the study. The lipid profile parameters with the calculation of the atherogenic coefficient; reduced and oxidized glutathione levels with the calculation of their ratio, the glutathione S-transferase and glutathione reductase activities were determined in the blood. Overweight women showed an increase in the triacylglycerols (p = 0.041) and cholesterol in very low density lipoproteins levels (p = 0.044). When assessing the glutathione system activity in women of the main group, compared with the control, an increase in the glutathione-S-transferase (p = 0.023) and glutathione reductase (p = 0.022) activities was noted, however, the reduced and oxidized glutathione levels, as well as their ratio did not differ from the control values. The results obtained indicate the activation of the glutathione system enzymatic link in response to changes in lipid status in postmenopausal women with overweight.

Serum Serotonin as a Biomarker of the Efficacy of PAP-Therapy in Sleep Apnea Syndrome.

Serum serotonin levels were determined by HPLC in 30 patients with diagnosed obstructive sleep apnea syndrome before and after 3-month course of PAP-therapy and in 14 subjects without obstructive sleep apnea symptoms. It was found that elimination of hypoxic conditions was associated with an increase in serotonin level. The results demonstrate the effectiveness of PAP-therapy during sleep and allow assessing the role of serotonin as a potential biomarker of intermittent hypoxia during sleep.

[Aging and cognitive disorders from the somnology's viewpoint.]

Age-dependent diseases high social burden makes relevant medical technologies development and implementation of human aging process functional state various disorders prenosological diagnosis, treatment and prevention. Age-related activity decrease of the brain functional state and its interdependence with the sleep-wake continuum leads to premature (pathological) aging with manifestations of neurodegeneration. Although disturbances of the sleep-wake cycle functioning are characteristic for the aging process, age-related changes are not always accompanied by cognitive dysfunction. There are sufficient number studies on the molecular level changes in age-related sleep disorders. Aging, sleep disorders and processes of cognitive dysfunction association pathogenetic mechanisms heterogeneity also include metabolism changes. Various neurotransmitters and other biologically active substances, so-called «sleep-promoting substances¼ are involved in the regulation of sleep processes. The urgent need for molecular-cell markers and diagnostic patterns of sleep disorders further scientific search in aging process is promising and will make a significant contribution to the breakthrough technologies development in the pathological aging prevention. The complex architecture of sleep undergoes pronounced changes throughout a person's life. In the literature, the relationship of circadian rhythm disturbances during aging and the development of cognitive dysfunction is actively debated. Approach from the positions of the modern neurobiology, somnology and sleep medicine perspectives seems extremely relevant and timely. This review is devoted to some aspects of age-related in sleep and their molecular-cell markers changes modern scientific research and our own data analysis.

8-Hydroxy-2'-Deoxyguanosine as an Oxidative Stress Marker in Insomnia.

We performed comparative analysis of 8-hydroxy-2'-deoxyguanosine in women in different climax stages with and without insomnia. The study involved 90 women aged 45 to 60 years divided into perimenopausal (n=30) and postmenopausal (n=60) groups. After questioning using special sleep questionnaires (Insomnia Severity Index, Epworth Sleepiness Scale, Munich Chronotype Questionnaire), the groups were divided into subgroups with insomnia and without it (control). 8-Hydroxy-2'-deoxyguanosine was assayed in blood serum by ELISA. The higher levels of 8-hydroxy-2'-deoxyguanosine in postmenopausal women with insomnia in comparison with the control and perimenopausal patients (p<0.05) attested to oxidative DNA damage in this cohort of patients.