[Effect of components of the renin-angiotensin system, rs2106809 polymorphism of the ACE2 gene, and therapy with RAS blockers on the severity of COVID-19].

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS), providing counter-regulation of its effects and, simultaneously, a receptor for the SARS-CoV-2 entering. It is suggested that factors regulating the balance of the major components of RAS, including ACE2 gene polymorphism, therapy with RAS blockers (ACE inhibitors and angiotensin receptor blockers) - may affect the severity of COVID-19. AIM: The aim of the study was to investigate the effect of RAS components, the relationship of ACE2 gene polymorphism rs2106809 and ACEi/ARBs therapy with the COVID-19 severity. MATERIALS AND METHODS: The study included patients with COVID-19 hospitalized in Endocrinology research centre (n = 173), who were divided into groups of moderate and severe course. Determination of RAS components was performed by ELISA, identification of polymorphism by PCR. Statistical analysis was performed using nonparametric statistical methods; differences in the distribution of genotype frequencies were assessed using Fisher's exact test χ2. RESULTS: The groups differed significantly in age, blood glucose levels, and inflammatory markers: leukocytes, neutrophils, IL-6, D-dimer, C-reactive protein, ferritin and liver enzymes, which correlated with the severity of the disease. When comparing patients in terms of ACE, ACE2, angiotensin II, ADAM17 there were no statistically significant differences between the groups (p=0.544, p=0.054, p=0.836, p=1.0, respectively), including the distribution by gender (in men: p=0.695, p=0.726, p=0.824, p=0.512; in women: p=0.873, p=0.196, p=0.150, p=0.937). Analysis of the distribution of AA, AG, and GG genotypes of the rs2106809 polymorphism of the ACE2 gene also revealed no differences between patients: χ2 1.35, p=0.071 in men, χ2 5.28, p=0.244 in women. There were no significant differences in the use of RAS blockers between groups with different course severity: χ2 0.208, p=0.648 for ACEi, χ2 1.15, p=0.283 for ARBs. CONCLUSION: In our study, the influence of activation of RAS components (ACE, ACE2, AT II, ADAM17) and ACE2 gene polymorphism on the severity of COVID-19 course was not confirmed. The severity of COVID-19 course correlated with the level of standard inflammatory markers, indicating the general principles of the infection as a systemic inflammation, regardless of the genetic and functional status of the RAS.

[The problem of iodine deficiency in the Chechen republic: assessment of the current state and ways of solution].

Iodine deficiency disorders (IDD) are prevalent and highly morbidity, have hidden progression, severe disabling somatic complications, including cognitive disorders, reproductive losses, and oncopathology. This presents a serious challenge to the healthcare system of the Russian Federation, as it affects over 3 million people. The lack of relevant data on the severity of IDD and the current prevention programs at the regional level necessitates the need for appropriate research and measures in individual subjects of the Russian Federation. AIM: To conduct a comprehensive study to assess the current iodine security of the population of the Chechen Republic, to analyze the prevalence of thyroid pathology and compare it with official statistics, to formulate conclusions about the necessary preventive measures. MATERIALS AND METHODS: In the Chechen Republic, a total of 1239 people were examined, of which 921 were schoolchildren of pre-pubertal age (8-10 years) and 318 were adults. The survey of the adult population was carried out at medical organizations in four districts of the republic (Nadterechny, Shalinsky, Vedensky, Grozny) and included a questionnaire survey, a clinical examination by an endocrinologist with palpation of the thyroid gland, thyroid ultrasound, and a study by a qualitative method of samples of table salt used in households for the presence of iodine.Children's examinations were carried out by the cluster method on the basis of secondary schools in 9 out of 15 districts of the republic and included an examination by an endocrinologist and measurement of anthropometric parameters (height, weight), thyroid ultrasound to evaluate volume, determination of iodine concentration in single portions of urine and qualitative analysis of samples of table salt used in children's nutrition in families for the presence of iodine.The incidence and prevalence of thyroid disease among the population of the Chechen Republic were analyzed using data from official state statistics - form No. 12 «Information on the number of diseases registered in patients living in the area served by the medical institution¼ (ROSSTAT data as of 01.01.2021). RESULTS: According to the results of a survey of 921 pre-pubertal children, the median urinary iodine concentration was 71.3 µg/L (frequency of values below 50µg/L - 17,7%) and varies from 48.9 to 179.2 µg/L in the surveyed areas. According to thyroid ultrasound data, diffuse goiter was detected in 16.4% of the examined children, with goiter frequency ranging from 11.3% to 23.5%. The proportion of iodized salt consumed in schoolchildren's families was 4.2% in all study areas (range of values from 1.3% to 8%), which indicates an extremely low level of using iodized salt by household.According to the results of the examination of the adult population (n=318), structural changes in thyroid tissue were detected in 79.9% (n=254), while the proportion of nodular thyroid pathology being 83% (n=205), with a range of values across different districts of 52.5-80%. CONCLUSION: Based on the obtained data, according to WHO criteria, it can be stated that, overall, the degree of severity of iodine deficiency disorders in the Chechen Republic corresponds to mild severity with a tendency towards moderate severity in several districts of the foothills. The results of the examination of the adult population indicate a high prevalence of thyroid pathology, predominantly nodular, in the Chechen Republic. The data obtained in the course of large-scale research made it possible to initiate the development of necessary medical and organizational measures in the region - a program for the prevention of IDD.

[Adipomyokines in children with obesity].

BACKGROUND: Adipomyokines are synthesized and secreted into the bloodstream by cells of both muscle and adipose tissue. They can have both a negative metabolic effect, acting as pro-inflammatory adipokines in obesity, and a positive one, increasing in response to physical exertion in the form of myokines. AIM: To study the features of adipocytokine secretion in children with constitutionally exogenous obesity. MATERIALS AND METHODS: The study included 80 patients: 60 adolescents aged 15 [13; 16] years with constitutionally exogenous obesity SDS BMI: 3.0 [2.6; 3.3] and 20 control group children aged 16 [15; 17] years without excess weight SDS BMI: -0.3 [-1.25; 0.33]. Commercial enzyme immunoassay kits were used to determine the level of adipomyokines. The compositional composition of the body was evaluated by bioimpedance analysis (InBody 770 analyzer, South Korea) in the morning, on an empty stomach. Statistical processing was carried out using STATISTICA v.12.0 (StatSoft Inc., USA). The results are presented in the form of median (Me) and quartiles (Q1; Q3) corresponding to 25 and 75 percentiles. The critical significance level (p) was assumed to be <0.05. RESULTS: Levels of IL-6 and irisin are statistically significantly higher in obese adolescents compared to the control group: 0.55 [0.226; 1.35] pg/ml vs 0.202 [0.128; 0.652] pg/ml (p=0.041) and 11.16 [6.6; 22.76] mcg/ml vs 7.36 [6.48; 9.68] mcg/ml (p=0.043), respectively. Concentrations of IL-6, myostatin and decorin increase with an increase in the degree of obesity: grade I vs III: 0.226 [0.224; 0.398] vs 0.80 [0.36; 1.81] pg/ml (p=0,0197), 25,85 [21,53; 28,23] vs 31.41 [24.36; 35.06] ng/ml (p=0.03), 4065.3 [3244.9; 5245.5] vs 5322.5 [4199.8; 7702.4] pg/ml (p=0.0376), respectively. In obese children, IL-6 levels positively correlate with BMI, SDS BMI and the amount of adipose tissue, and myostatin - with BMI and SDS BMI. The concentration of irisin in the blood serum is significantly higher in obese girls than in obese boys and healthy girls. Obese patients, compared with lean peers, are characterized by a statistically significantly higher content of both fat and lean mass. With the progression of obesity, there is a statistically significant increase in the ratio of fat to lean mass (I degree - 0.66 [0.56; 0.7], III - 0.78 [0.68; 0.98] (p=0.0073). CONCLUSION: Patients with obesity and normal body weight have different levels of adipomyokines. An increase in the level of IL-6 with the progression of obesity is directly related to an increase in the content of adipose tissue. Further study of the features of adipocytokine secretion, their relationship with the features of the body composition and metabolic complications in obesity is required.

[Determination of prolactin reference intervals in different age groups].

BACKGROUND: Clinical diagnostic laboratories (CDL) have at their disposal various automated systems for the measurement of biochemical parameters and markers such as prolactin. Each of the test systems manufactures offers its own alternate design of the method, which makes standardization difficult. In endocrinological practice, the problem of result discrepancies often arises. In hormonal assays, the clinical picture of patients sometimes does not correspond to the reference values provided by the manufacturers, which determines the need to develop the method-specific reference values for a specific population. The difficulty in interpreting basal prolactin levels is not only due to a transient increase in the hormone levels caused by stress or excessive physical exertion, but also due to a significant variability of indicators in the same patient, even if all recommendations for blood sampling are followed. AIM: The aim of the study to determine the reference values in serum samples of women, men and children of different age groups for the VITROS Immunodiagnostic Systems and compare the results with the "expected prolactin levels" recommended by the method manufacturerMATERIALS AND METHODS: The monocentric study included 879 serum samples of apparently healthy subjects who were admitted to the Endocrinology Research Center. Measurements were performed using the VITROS ECi 3600 automatic chemiluminescence analyzer (Ortho-Clinical Diagnostics, Great Britain). RESULTS: For adult men and women reference values were 66-436 and 94-500 mIU/l respectively. When comparing the results of prolactin determination in women and men of the studied cohort with the "expected values" of the VITROS ECi 3600 manufacturer a systematic shift towards an increase in lower and upper limits of the reference values was found in both -cohorts. CONCLUSION: The obtained reference values of prolactin can be use in the determination of prolactin in the Russian population for VITROS ECi 3600 Immunodiagnostic Systems.

[Calcitonin measurement in fine-needle washout fluids in detecting medullary thyroid cancer].

BACKGROUND: The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy wash-out fluid is a promising tool in the diagnosis of medullary thyroid cancer. AIMS: We assessed the potential usefulness and the diagnostic significance of Ct-FNAB alone in comparison with cytology in the diagnosis and localization of primary or metastatic MTC. MATERIALS AND METHODS: For this purpose, we retrospectively examined data from 67 patients with suspicious thyroid nodules and/or lymph nodes who ultimately underwent surgical treatment at the Endocrinology Research Centre in 2015-2020. The primary endpoint of the study was to evaluate the diagnostic accuracy of Ct-FNAB when compared to cytological examination. The secondary endpoint was to determine the optimal diagnostic level for use in clinical practice. RESULTS: The obtained results showed that high Ct-FNAB concentrations were present in all histologically proven MTC, either in thyroid gland (sensitivity 92.5%, specificity 100%) or neck masses (sensitivity 88.5%, specificity 100%). The optimal diagnostic threshold for Ct-FNAB values from thyroid nodes was > 122 pg/ml, from lymph nodes >35.8 pg/ml. CONCLUSIONS: Our findings suggest that Ct-FNAB is a highly reliable diagnostic procedure to identify primary and recurrent/metastatic MTC. The actual relevance of this technique in the management of MTC needs further longitudinal studies in a larger number of patients.

[Dynamics of NT-proBNP and ST2 levels as markers of heart failure in patients with endogenous Cushing syndrome (hypercortisolism)].

AIM: To evaluate frequency of heart failure syndrome in patients with endogenous hypercortisolism and to establish relationship between effective treatment for hypercortisolism and regression of heart failure with particular emphasis on the observation of NT-proBNP and ST2 levels. MATERIALS AND METHODS: 56 patients with endogenous hypercortisolism (45 female, mean age 47 years [36; 55] hospitalized with endogenous hypercortisolism to National Medical Research Center for Endocrinology were enrolled in the study. All patients underwent comprehensive clinical investigation including expert echocardiography with speckle tracking and evaluation of NT-proBNP and ST2 cardiac biomarkers at baseline and 6 months after surgical treatment. RESULTS: According to clinical data and elevated biomarkers of cardiac stress 28 out of 56 patients (50%) at baseline met the criteria for heart failure. 20 patients were included in the final analysis. Follow-up investigation with focus on changes in NT-proBNP and ST2 levels demonstrated that surgical correction of endogenous hypercortisolism resulted in resolution of heart failure syndrome in 11 patients (55%). CONCLUSION: These preliminary data suggest that signs and symptoms of heart failure are observed in patients with endogenous hypercortisolism in about half the cases. Surgical correction results in resolution of heart failure in approximately two thirds of the cases. Prospective evaluation NT-proBNP and ST2 levels may provide important diagnostic and prognostic information in patients with endogenous hypercortisolism.

[Myokines in obese adolescents with aerobic exercise].

BACKGROUND: Myokines are synthesized by myocytes and released into the bloodstream in response to muscle fiber contraction. They have a positive effect on carbohydrate and lipid metabolism, muscle mass growth, osteogenesis, increase tissue sensitivity to insulin, counteract inflammation of adipose tissue. The study of their secretion in response to physical activity (FA) can help to personalize the therapy of obesity. AIM: to study the features of the secretion of myokines in children with constitutionally exogenous obesity during physical activity of different duration and intensity and to evaluate their relationship with the parameters of the body composition. MATERIALS AND METHODS: 26 children (10 boys and 16 girls) were included in the study 15 [13; 16] years old, SDS BMI: +2.91 [2.24; 3.29], with sexual development according to Tanner 4-5. Two groups of 13 people were formed by random distribution. Group I performed FA (walking on a treadmill under the control of heart rate) of different duration: 30 and 60 minutes at the same intensity (less than 3 metabolic equivalents (MET)). Group II - FA of different intensity: low - less than 3 METH and moderate - 3-6 METH with the same duration of 45 minutes. Commercial kits for enzyme immunoassay were used to determine the level of myokines. The assessment of the compositional composition of the body was carried out by bioimpedance analysis (analyzer In Body 770, South Korea) in the morning, on an empty stomach. Statistical processing was carried out using STATISTICA v.12.0 (StatSoftInc., USA). The results are presented in the form of median (Me) and quartiles (Q1; Q3) corresponding to 25 and 75 percentiles. The critical significance level (p) was assumed to be <0.05. RESULTS: moderate intensity FA leads to a maximum increase in the level of myokines: interleukin-6 (IL-6) by 215.7% and decorin by 34.3%, a decrease in the level of irisin by 16.5%. An hour-long low-intensity workout leads to a moderate increase in the level of IL-6 by 80.5%, to a decrease in the level of irisin by 31.1%. Myostatin increases equally both after 60-minute FA and after moderate intensity FA by 30.9% and 31.8%, respectively. Short low-intensity FA (lasting 30 minutes) it is not accompanied by a significant increase in the expression of myokines. The relationship between the amount of muscle (r=0.65), lean (r=0.62), fat-free mass (r=0.64) and the level of decorin after FA was noted. There was no statistically significant relationship between the parameters of the body composition and the levels of IL-6, myostatin, and irisin. There were no gender differences in both basal and stimulated myokine secretion. CONCLUSION: Moderate intensity FA and low intensity 60-minute FA are most effective for obese children. A 30-minute low-intensity FN is insufficient to increase the secretion of myokines by skeletal muscles.

Analytical platforms Vitros ECi 3600 and Cobas 6000: comparative analysis of prolactin measurement.

Prolactin is a polypeptide hormone secreted by the lactotrophic cells of the anterior pituitary gland and has a wide range of biological effects in the human body. Accurate measurements of prolactin concentration are essential in obtaining biochemical data to support clinical decisions in the diagnosis, treatment and prevention of diseases of the pituitary gland, reproductive, immune and other body systems. The aim of our study is to carry out a comparative analysis of the serum prolactin measurement determined by the two analytical platforms Vitros ECi 3600 (Ortho-Clinical Diagnostics) and Cobas 6000 (Roche). Serum samples from 664 patients undergoing examination at the Endocrinology Research Center were included in the study. Comparative analysis of serum prolactin measurement showed that results obtained by the two analytical systems are consistent with each other (r = 0.89, p<0,05). Clinically accuracy of prolactin measurement and to a large extent using the same method is of particular importance in primary diagnosis, treatment and long-term follow-up of the patient.

Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus.

AIM: The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). MATERIALS AND METHODS: The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. CONCLUSION: Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage.

[Urinary excretion of markers for podocyte injury in patients with diabetes mellitus]. / Ekskretsiya s mochoi markerov povrezhdeniya podotsitov u bol'nykh sakharnym diabetom.

AIM: To estimate the urinary excretion of markers for podocyte injury, to specify their value for the early diagnosis of diabetic nephropathy (DN), and to access the risk of its progression in patients with diabetes mellitus (DM) with varying degrees of albuminuria/proteinuria. SUBJECT AND METHODS: Seventy-four diabetic patients (30 with type 1 DM and 44 with type 2 DM) were examined and divided into 3 groups according to the urinary concentration in one urinary portion: 1) 41 patients with normal albuminuria (NAU) (<20 mg/l); 2) 13 patients with microalbuminuria (MAU) (20-200 mg/l); 3) 20 patients with proteinuria (PU) (>200 mg/l). A control group included 10 healthy individuals. The urinary levels of the podocyte structural proteins nephrin and podocin were determined by enzyme immunoassay. RESULTS: Nephrinuria (NU) was detected in 63, 77, and 80% of the patients with NAU, MAU, and PU, respectively. Podocinuria (PDU) was found in 78, 54, and 83% of those with NAU, MAU, and PU, respectively. NU in DN with PU was significantly higher than that in DM with NAU. In the NAU, MAU, and PU subgroups, podocin excretion was equally higher and did not differ between the types of DM. There was a direct correlation of NU with albuminuria, which was stronger in the MAU subgroup. In the patients with DM with varying degrees of albuminuria, the values of NU and PDU correlated directly to serum creatinine levels and inversely with glomerular filtration rate. NU directly correlated with glycated hemoglobin levels in the patients with types 1 and 2 DM of less than 5 years' duration and a direct significant correlation of systolic blood pressure with NU was found in those with type 2 DM. CONCLUSION: Determination of urinary nephrin and podocin levels may be used for the early preclinical diagnosis of DN and the monitoring of the glomerular apparatus in DM.

[Nonglycemic effects of incretins in patients with long-term type 1 diabetes mellitus and chronic kidney disease]. / Neglikemicheskie effekty inkretinov u patsientov s dlitel'nym techeniem sakharnogo diabeta 1-go tipa i khronicheskoi bolezn'yu pochek.

AIM: To investigate the nonglycemic effects of incretins in patients with type 1 diabetes mellitus (DM1) of long duration (for more than 20 years) and chronic kidney disease. MATERIAL AND METHODS: Seventy-five patients with varying degrees of diabetic nephropathy (DN) and without this condition, including patients receiving renal replacement therapy with programmed hemodialysis and those who had undergone kidney transplantation were examined. The levels of phosphorus-calcium metabolic indicators (calcium, phosphorus, parathyroid hormone, vitamin D, and fibroblast growth factor 23 (FGF-23)), the cardiac damage marker atrial natriuretic peptide, the proinflammatory markers monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and the fibrotic marker transforming growth factor-ß, as well as those of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were estimated in addition to conventional examination methods. All the patients underwent cardiac multislice spiral computed tomography, by calculating the Agatston index (calcium index (CI)) reflecting the degree of coronary artery calcification. RESULTS: The investigation revealed no relationship of GLP-1 and GIP levels to the presence and degree of DN in the patients of the study groups. GLP-1 was noted to be inversely related to patient age, indicating the diminished secretion of this peptide in older people. There was evidence that GLP-1 positively affected blood lipid composition (total cholesterol: r=-0,320; p<0.05) and the magnitude of coronary artery calcification (CI: r=-0.308; p<0.05). GIP showed a differently directed effect on the proinflammatory factors: fibrinogen (r=-0.264; p<0.05), CRP (r=-0.626; p<0.05), and FGF-23 (r=-0.341; p<0.05). CONCLUSION: The investigation has demonstrated the nonglycemic effects of incretins that favorably affect the pathogenetic processes underlying the late complications of DM1. The findings point to the potential efficacy of incretin-based drugs in preventing and treating the late complications of DM, which necessitates the conduction of larger investigations.