LIPID PEROXIDATION AND ANTIOXIDANT STATUS WITH REPRODUCTIVE DISORDERS

An. analysis the results were obtained in the laboratory of pathophysiology of reproduction, of Scientific Centre of Family Health, and Human Reproduction. Problems, SB RAMS clearly indicate that oxidative stress accompanies and. / or appears like a key pathogenetic link in the development of many types of reproductive disorders. We dedicate, that further researches of the roles of the system, «lipid, peroxidation. — antioxidant protection.» are needed. Moreover, there are good reasons for using of different antioxidants, but it should, be prescribed individually, taking into account of nature of oxidative imbalance

Синтез 5-оксиметил-1,2,4-триазол-3-карбоксамидов

Objectives. A key step in the synthesis of natural nucleoside analogs is the formation of a glycosidic bond between the carbohydrate fragment and the heterocyclic base. Glycosylation methods differ in terms of regio- and stereoselectivity. A promising method for the highly specific synthesis of new pharmacologically active compounds involves an enzymatic reaction catalyzed by genetically engineered nucleoside phosphorylases. This study is devoted to the synthesis of a library of analogs of nucleoside heterocyclic bases—5-oxymethyl-1,2,4-triazole- 3-carboxamides—in order to investigate the substrate specificity of genetically engineered nucleoside phosphorylases.Methods. A method of cyclization of acylamidrazones obtained from the single synthetic precursor β-N-tert-butyloxycarbonyl-oxalamidrazone was used to parallel-synthesize new 5-alkoxy/ aryloxymethyl-1,2,4-triazole-3-carboxamides. Silica gel column chromatography was used to isolate and purify the synthesized compounds. A complex of physicochemical analysis methods (nuclear magnetic resonance spectroscopy, chromatography, and mass spectrometry) confirmed the structure of the compounds obtained in the work.Results. 5-alkoxy/aryloxymethyl-1,2,4-triazole-3-carboxamides were obtained to study the substrate specificity of genetically engineered nucleoside phosphorylases. The possibility of obtaining new nucleoside analogs by the chemico-enzymatic method was demonstrated on the basis of preliminary assessment results.Conclusions. The physicochemical characteristics of a series of novel 5-alkoxy/aryloxymethyl- 1,2,4-triazole-3-carboxamides were studied along with their potential to act as substrates for the transglycosylation reaction catalyzed by nucleoside phosphorylases.Цели. Ключевая стадия синтеза аналогов природных нуклеозидов – образование гликозидной связи между углеводным фрагментом и гетероциклическим основанием. Методы гликозилирования различаются по регио- и стереоселективности. Ферментативная реакция, катализируемая генно-инженерными нуклеозидфосфорилазами – перспективный метод высокоспецифичного синтеза новых фармакологически активных соединений. Данное исследование посвящено синтезу библиотеки аналогов гетероциклических оснований нуклеозидов – 5-оксиметил-1,2,4-триазол-3-карбоксамидов для изучения субстратной специфичности генно-инженерных нуклеозидфосфорилаз.Методы. Для параллельного синтеза новых 5-алкокси/арилоксиметил 1,2,4-триазол3-карбоксамидов применен метод циклизации ациламидразонов, получаемых из единого синтетического предшественника – β-N-третбутилоксикарбонил-оксаламидразона. Для выделения и очистки синтезированных соединений использована колоночная хроматография на силикагеле. Структура полученных в работе соединений подтверждена комплексом методов физико-химического анализа: спектроскопией ядерного магнитного резонанса и хромато-масс-спектрометрометрией.Результаты. Получены 5-алкокси/арилоксиметил-1,2,4-триазол-3-карбоксамиды для изучения субстратной специфичности генно-инженерных нуклеозидфосфорилаз. По результатам предварительной оценки показана возможность получения из них новых аналогов нуклеозидов химико-ферментативным методом.Выводы. Для серии новых 5-алкокси/арилоксиметил-1,2,4-триазол-3-карбоксамидов изучены физико-химические характеристики, а также их способность выступать в роли субстратов реакции трансгликозилирования, катализируемой нуклеозидфосфорилазами

Markers of oxidative damage lipids and DNA in men with type 1 diabetes mellitus and different levels of albuminuria

BACKGROUND: Diabetic nephropathy is a specific kidney damage that affects up to 40% of type 1 diabetes mellitus patients. There is still insufficient knowledge about oxidative stress at the different levels of albuminuria.AIM: To assess the indicators of oxidative damage to lipids, DNA and antioxidant defense in men with type 1 diabetes mellitus and albuminuria different levels.MATERIALS AND METHODS: The study was conducted during 2018–2019. The main group included 56 men of reproductive age with type 1 diabetes mellitus (T1DM) divided into 2 groups: 24 patients with albuminuria level A1 (group A1) and 32 patients with albuminuria level A2 (group A2). The control group consisted of 28 healthy men. The oxidative stress indicators content, as well as the activity of antioxidant defense system various links was evaluated. Spectrophotometric, fluorimetric and enzyme immunoassay methods were used.RESULTS: In patients of the A1 group there were higher values of the median of primary — conjugated dienes, secondary — ketodienes and conjugated trienes, final — Schiff bases products and 8-hydroxy-2’-deoxyguanosine in comparison with the control. Similar changes in patients of the A2 group were found. Intergroup differences related to increased median values of TBARs and 8-hydroxy-2’-deoxyguanosine in patients of the A2 group compared with A1 group. The activity of the antioxidant defense system in A1 group relative to the control by increased values of the glutathione peroxidase, reduced glutathione, oxidized glutathione median, and retinol was characterized. A2 group had higher values of glutathione peroxidase, reduced glutathione and oxidized glutathione medians in comparison with controls. Correlation analysis in A1 group showed the relationships between the duration of the disease and the products of lipid peroxidation, glycated hemoglobin with 8-hydroxy-2’-deoxyguanosine. In A2 group, there was a relationship between the albumin/creatinine ratio and the duration of the disease, glomerular filtration rate and creatinine level.CONCLUSION: In men with T1DM, regardless of the albuminuria level, there are higher values of the oxidative damage lipids and DNA parameters, as well as the presence of close relationships between these parameters and the duration of the disease, which can be used to develop potential strategies for the prevention and early therapy of diabetic nephropathy

THE CHANGES OF FUNCTIONAL ACTIVITY OF A THYROID AND METABOLISM OF THYROID HORMONES IN TEENAGED GIRLS IN DIFFERENT ETHNIC GROUPS OF EASTERN SIBERIA AS AN IMPORTANT COMPONENT OF LONG-TERM ADAPTATION TO EXTREME CLIMATIC AND GEOGRAPHICAL CONDITIONS OF LIVING

Girls and teenaged girls of different ethnic groups living in Tofalaria during different age period were examined. The aim of this research was to establish the peculiarities of functioning of pituitary-thyroid system and metabolism of thyroid hormones in healthy girls and teenagers living under adverse climatic and geographical conditions depending on their ethnicity. It was set that in ethnic Tofs girls and in Europoids girls in age group of 7-11 there were differences in the content of the active fractions of thyroid hormones testifying different mechanisms of maintenance of thyroid homeostasis. These differences remain in age group of 12-14, when changes in pituitary section of the system are added to them. The functioning of pituitary-thyroid system-level of neuro-endocrine regulation in native girls of Tofalaria of 15-18 goes in more economical way. This is actually the result of genetically determined long-term adaptation of natives' organism to extreme climatic and geographical environmental factors

FEATURES OF ANTIOXIDANT SYSTEM STATE IN ADOLESCENTS OF EASTERN SIBERIA IN DEPENDS ON THEIR GENDER AND ETHNIC ORIGIN

This research is devoted to studying of features of antioxidant protection system in adolescent boys and girls of various ethnic groups of Eastern Siberia. Study of the peculiarities of processes of antioxidant protection of populations of people of different ethnicity, living in the same geographical conditions, is of undoubted scientific interest. It is especially important to assess metabolic status of a young, growing body to ensure in the future the preservation of reproductive ability. We biochemically evaluated 58 boys of 14-17 years old. Out of them 19 boys were Russian, 29 boys were Buryat population and 10 boys were metises. Also we biochemically evaluated 57 girls. Out of them 21 were Russian, 27 girls were Buryat population and 9 girls were metises. The materials for biochemical studies were blood serum and red cells. The total antioxidant activity of serum and the content of its components (superoxide dismutase, α-tocopherol, retinol, blood-reduced glutathione) were evaluatedbya spectrofluomphotometer «SHIMADZU-1501» (Japan). Statistical analysis was performed by parametric tests. The study was supported by grants of the President ofthe Council of the Russian Federation (Scientific School 494.2012.7). The detected features of antioxidant protection processes in observed adolescents had gender differences, also may be explained by their ethnicity and characterized by different degree of activity of metabolic processes in adolescent boys and girls of different ethnic groups of Eastern Siberia. Study the state of the antioxidant system of the organism can be used as an additional criterion for complex examination of practically healthy adolescents, which significantly enhance the representation about the adaptation possibilities of the organism to external conditions and can be a basis for effective monitoring of reproductive health in the future

Показатели метаболического статуса у подростков тофаларов, представителей малого коренного этноса Восточной Сибири

The aim of the work is to study the state of health and peculiarities of metabolic reactions in adolescents, representatives of the small Siberian ethnos - tofalars and caucasians.Materials and methods. Clinico-biochemical examination of children and adolescents, representatives of a small ethnic group – Тofalars and Caucasians, permanently residing in the territory of Tofalaria in the Irkutsk region. The metabolic status of adolescents was assessed using spectrophotometric (total cholesterol, diene conjugates), fluorometric (superoxide dismutase activity, α-tocopherol and retinol levels), immunoenzymes (determination of thyroid-stimulating hormone concentrations, free fractions of triiodothyronine and thyroxine, cortisol).Results. An increased incidence of diseases of the musculoskeletal system and connective tissue, as well as diseases of the endocrine system and eating disorders – among Тofalars; diseases of the genitourinary system – among Сaucasians. For practically healthy Тofalar teenagers, in contrast to Сaucasians of the newcomer population, adaptive metabolism reactions are characteristic, which is expressed by a reduced level of total cholesterol and increased values of antioxidant factors (the level of fat-soluble vitamins – α-tocopherol and retinol), and adaptive changes in the system of neuroendocrine regulation.Сonclusion. An assessment of the health status of children and adolescents in Tofalaria has shown the need for more intensive monitoring of the incidence rate in the specified region, with the obligatory consideration of the ethnic factor for the development of regional ethno-specific preventive measures. Цель работы – изучение состояния здоровья и особенностей метаболических реакций у подростков, представителей малого сибирского этноса тофаларов и европеоидов пришлого населения.Материалы и методы. Проведено клинико-биохимическое обследование детей и подростков – представителей малой народности тофаларов – и европеоидов, постоянно проживающих на территории Тофаларии в Иркутской области. Метаболический статус подростков оценивали с помощью спектрофотометрических (содержание общего холестерина, диеновых конъюгатов), флуориметрических (активность супероксиддисмутазы, уровни α-токоферола и ретинола), иммуноферментных (определение концентраций тиреотропного гормона, свободных фракций трийодтиронина и тироксина, кортизола) методов исследования.Результаты. Отмечена повышенная частота встречаемости заболеваний костно-мышечной системы и соединительной ткани, а также болезней эндокринной системы и расстройства питания (среди тофаларов); заболеваний мочеполовой системы (среди европеоидов). Для практически здоровых подростков тофаларов, в отличие от европеоидов пришлого населения, характерны адаптивные реакции метаболизма, что выражается сниженным уровнем общего холестерина и повышенными значениями антиоксидантных факторов (уровня жирорастворимых витаминов – α-токоферола и ретинола), а также адаптивными изменениями в системе нейроэндокринной регуляции.Заключение. Оценка состояния здоровья детей и подростков Тофаларии показала необходимость проведения более интенсивного мониторинга уровня заболеваемости в указанном регионе с обязательным учетом этнического фактора для разработки региональных этноспецифических мероприятий по профилактике заболеваний.

The influence of the heliogeophysical factors on the clotting of blood of pregnant women with placental insufficiency

Geomagnetic storms are one of the natural abiotic risk factors for human health. The response of the organism to their impact depends on the individual adaptive abilities, which were formed during the evolution, but can change in the conditions of pathological processes. Evaluation of the effect of a weak magnetic storm (G4v (22 < Ar < 39 nTl) on hemorheological parameters of blood of pregnant women with placental insufficiency compared to healthy pregnant women showed an increase in platelet count (p = 0.05), fibrinogen content (p = 0.02), thrombocyte (p = 0.03), erythrocyte sedimentation rate (p = 0.004). At the same time, a decrease in the number of red blood cells (p = 0.04), hemoglobin concentration (p = 0.001), hematocrit value (p = 0.0009) was registered. We found a strong direct correlation between subpopulations of platelets, which are characterized by different functional activity. Heterogeneity of platelets, their multidirectional correlations with indicators of blood coagulation system of healthy pregnant women can be considered as a response to the change in the disturbance of the earth's magnetic field. For pregnant women with placental disorders, the magnetic storm was associated with increased activity of the blood coagulation system and a significant increase in its components in the blood of patients. Despite the fact that changes in the blood coagulation system occur from the beginning of pregnancy and are often adaptive, in pregnant women with placental disorders, the additional impact of a weak magnetic storm can be a risk of hemostasis disorders and the development of platelet thrombosis, timely diagnosis and therapy of which is important

Results of implementation of viral hepatitis B elimination program in the North-West Russia

Introduction. Vaccination contributed to reduce the incidence of acute hepatitis B in the territories of the North-West Russia. The urgency of this problem remains due to the high incidence of chronic hepatitis B. This accounted for the need to develop a hepatitis B elimination program in the district discussed that was approved in 2013 by the head of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing. Objective is to characterize the results of the program for the elimination of acute hepatitis B virus implemented in the North-Western Federal District. Materials and methods. The 2010–2020 incidence rate of acute and chronic hepatitis B virus (HBV) infection in the regions of the North-West Russia was carried out. To determine HBV genotypes and subgenotypes, 160 blood plasma samples from patients with acute hepatitis B were studied using molecular genetic methods (PCR, sequencing). The prevalence of latent hepatitis B in various population groups was assessed. The 2016–2020 hepatitis B vaccination coverage and relevant serological monitoring in adults was carried out. Results. While implementing the program, it was found that the incidence rate of acute hepatitis B in the district decreased by 4.5-fold, revealing in 2020 no cases of the disease in 5 regions, with incidence rate in the 6 subfederal units being lower than 1.0 per 100,000 population. Moreover, the incidence rate for chronic hepatitis B decreased by 2.6 times. The 2020 vaccination coverage of children under 17 and adults in all territories comprised more than 95% and 90%, respectively. In addition, it was shown the circulation of genotypes D and A of hepatitis B virus is dominated by genotype D (91.8%), subgenotype D2 (47.8%). The prevalence of latent hepatitis B among migrants was 6.5%, pregnant women — 4.9%, hemodialysis patients — 1.7%. Conclusion. Implementation of the program on elimination of acute viral hepatitis B in the territory of the North-West Russia contributed to raise in the vaccination coverage in adult population and lowered incidence rate of acute and chronic HBV infection

Сравнительная оценка эффективности базисных препаратов при лечениидетей и подростков с различными вариантами ювенильного идиопатического артрита

Objective. To specify the diagnosis of juvenile idiopathic arthritis (JIA) and to define the significance of pathogenetic changes, the authors have studied cellular and humoral immunological parameters, which are of the greatest informative value in this pathology: CD4+, CD4+/CD8+, CD8+, CD16+, CD95+ in the serum, as well as a spectrum of interleukins (IL): tumor necrosis factor-а, IL-6, IL-1, and IL-4. Subjects and methods. An optimal basic drug was selected for a specific form of JIA. Preference is given to cyclosporine and methorexate (MT) in its polyarticular form with the high activity of an inflammatory process, to MT, cyclosporine A, and auranofin in the disseminated form of oligoarthritis, and to auranofin and sulfasalazine in the persistent form. Results. None of the basic drugs is superior while individually choosing a treatment and this or that drug has to be very frequently chosen empiricallyЦель исследования. Для уточнения диагноза ювенильного идиопатического артрита (ЮИА) и определения значения патогенетических изменений исследовали показатели клеточного и гуморального иммунитета, наиболее информативные при данной патологии: CD4+, CD4+/CD8+, CD8+, CD16+, CD95+ в сыворотке крови, а также спектр интерлейкинов (ИЛ): ФНО а, ИЛ 6, ИЛ 1, ИЛ 4. Материал и методы. Для конкретной формы ЮИА подбирали оптимальный базисный препарат. При полиартикулярной форме с высокой степенью активности воспалительного процесса предпочтение отдавали циклоспорину и метотрексату (МТ); при распространяющемся варианте олигоартрита - МТ, циклоспорину А (ЦсА), ауранофину, при персистирующем варианте - ауранофину, сульфасалазину. Результаты исследования. Ни один из базисных препаратов не являлся исключительным при индивидуальном подборе лечения, и очень часто в ходе лечения приходилось эмпирически подбирать тот или иной препарат