No abstract

Long-term complications of type 1 diabetes mellitus (T1DM) in children and adolescents are an important problem in modern medicine. Recently, the role of immune mechanisms, in particular, chronic inflammation, in the development of both T1DM and its microvascular complications has been actively discussed. Activation of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) leads to hyperproduction of proinflammatory cytokines, chemokines, adhesion molecules involved in the formation of diabetic microvascular complications. At the same time, TLR2 and TLR4 gene polymorphism alters the immune susceptibility to the endogenous ligands, which may increase the risk of diabetic microangiopathies. The aim of this study is to evaluate the frequency of genotypes and alleles of TLR2 and TLR4 genes distribution and to determine the content of TNFα, IL-1, VCAM-1, fractalkine, endothelin-1 in adolescents with T1DM with microvascular complications. We examined 139 adolescents with T1DM from 14 to 18 years old and 56 healthy teenagers. Patients with T1DM were divided into two groups: Group I – patients with poor glycemic control (HbA1C > 9.0%), (n = 64); Group II – patients with satisfactory glycemic control of T1DM (HbA1C ≤ 9.0%), (n = 75), including adolescents with optimal (HbA1C < 7.5%) and suboptimal glycemic control (7.5% ≤ HbA1C ≤ 9.0%) (ISPAD clinical practice consensus guidelines 2014). According to the presence of microvascular complications, the groups were subdivided into subgroups: Iа (n = 49), IIа (n = 38) – adolescents with verified microvascular disorders: diabetic retinopathy, nephropathy and neuropathy; Ib (n = 15), IIb (n = 37) – without microvascular complications. Allelic variants of TLR genes were determined using test systems GosNII genetics (Moscow). The content of cytokines in blood serum was carried out by the method of enzyme-linked immunosorbent assay “BIOSCIENCE”. Data were analyzed using software packages Statistica version 6.0. The assessment of TLR2 (Arg753Gln) and TLR4 (Thr399Ile) polymorphism distribution did not reveal significant differences between the observed subgroups and the control. In Ia and IIa subgroups (with complications) Asp299Gly variant was noted to be significantly less common when compared to subgroups Ib, IIb and controls. The presence of Gly allele in TLR4 gene was found to disrupt the expression of TNFα and VCAM-1 and can be considered protective for the development of microvascular complications.

акушерства и педиатрии (дир.-д.м.н. А.А. Лебеденко) ФГБОУ ВО «Ростовский государственный медицинский университет» Минздрава России, Ростов-на-Дону, Россия; 2 ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. Отта» (врио дир.-член-корр. РАН, д.м.н., проф. И.Ю. Коган) Минздрава России, Санкт-Петербург, Россия; 3 ФГБОУ ВО «Ставропольский государственный медицинский университет» (ректор-д.м.н., проф. В.И. Кошель) Минздрава России, Ставрополь, Россия В некоторых исследованиях указано на участие ряда цитокинов в процессе родовой деятельности и продемонстрирована связь между наступлением родов и усилением продукции некоторых цитокинов. Цель исследования-определение значения продукции цитокинов и окситоцина в прогнозировании течения родов и решении вопроса о выборе тактики родоразрешения у беременных с сахарным диабетом 1-го типа. Материал и методы. Обследованы 45 беременных с физиологическим течением беременности и родов (контрольная группа) и 40 беременных с ранее существовавшим сахарным диабетом 1-го типа (основная группа). Наблюдение и обследование беременных проводились в динамике I (12 нед), II (24-28 нед), III (36-38 нед) триместров беременности по программе «Акушерский мониторинг» с 2016 по 2018 г. В сыворотке крови пациенток основной и контрольной групп накануне предполагаемых родов (37-38 нед беременности) определяли уровни интерлейкина-1-β (ИЛ-1β), фактора некроза опухолей альфа (ФНО-α), трансформирующего фактора роста β (ТФР-β) и окситоцина методом иммуноферментного анализа. Результаты. Установлено, что аномалии родовой деятельности развились у 87,5% беременных с сахарным диабетом 1-го типа. Неэффективность родостимуляции у рожениц основной группы при первичной и/или вторичной слабости родовых сил составляла 12,5%. При этом у беременных с сахарным диабетом 1-го типа выявлено повышение уровня ИЛ-1β, ТФР-β, ФНО-α (на 100, 58 и 51% соответственно) накануне родов на фоне снижения уровня окситоцина (на 80%). Заключение. Выявлены сильные корреляции между биохимическими маркерами (ИЛ-1β, ТФР-β, ФНО-α, окситоцином) и сократительной активностью матки (r=0,8) у пациенток основной группы, что позволяет прогнозировать высокую вероятность развития аномалий родовой деятельности и тактику родоразрешения.

Objective. To develop prognostic criteria for the chronic course of cytomegalovirus infection by studying disorders of the regulation of the immune response in children of the first year of life against the background of hypoxic-ischemic CNS damage.Materials and methods. 108 newborns with cytomegalovirus infection occurring against the background of perinatal hypoxicischemic lesions of the central unequal system were examined. All observed patients at 1 and 3 months of life conducted an immunological examination, including the determination of T and B-lymphocytes. Determination of the population and subpopulation composition of peripheral blood lymphocytes, activation markers was carried out by the method of one- and twoparameter phenotyping using reagents from Immunotex (France), FITC (fluorescein isothiocynate) — labeled with CD3+, CD4+, CD8+, CD20+ and PE (phycoerythrin) — labeled CD28+, CD40+. The results were recorded on a BECKMAN COULTER EPICSXL-II flow cytometer (USA) using standard protocols. The observation groups consisted of 78 children (72.2%) with an acute course of the disease (Group 1) and 30 children (27.3%) with a chronic course (Group 2).Results. Of the totality of the studied parameters of the cellular and humoral parts of the immune system, statistically significant for the prognosis of the chronic course of cytomegalovirus infection in children of the first year of life against the background of hypoxic-ischemic CNS damage were found: CD8, CD40, CD3+CD28+, CD20+CD40+. Using the PolyAnalist 3.5 Pro CNS package, systems of inequalities were obtained and a formula for predicting the chronic course of cytomegalovirus infection in children in the first year against the background of perinatal hypoxic-ischemic CNS damage was calculated.Conclusion. A statistically significant relationship was found between the prognosis of the chronic course of cytomegalovirus infection against the background of perinatal hypoxic-ischemic CNS damage and the level of CD20, CD4, costimulatory molecules CD3+CD28–, CD20+CD40+. The proposed diagnostic rules can be considered screening markers for the prognosis of the chronic course of cytomegalovirus infection against the background of perinatal hypoxic-ischemic CNS damage in newborns, which makes it possible to start specific therapy in a timely manner.

The problem of intrauterine growth retardation is currently relevant, as it is one of the causes of neonatal morbidity and mortality. Purpose. To study the course of the neonatal period and evaluate the content of arginine and glutamic acid in full-term newborns depending on the severity of intrauterine growth retardation.Material and methods. 78 full-term newborns with intrauterine growth retardation according to hypotrophic type were examined. The content of glutamic acid and arginine in blood serum was determined in the early neonatal period by capillary electrophoresis using an unmodified quartz capillary (Kapel-105, Lumeks, St. Petersburg, Russia).Results. Markers of the formation of a severe degree of intrauterine growth retardation were identified: increased levels of glutamic acid and arginine, taking into account impaired cerebral blood flow in the early neonatal period. A model is proposed for predicting the persistence of a severe degree of intrauterine growth retardation in newborns by the end of the neonatal period.Conclusion. The proposed diagnostic criteria make it possible to start specific therapy in a timely manner in order to prevent the formation of a severe degree of intrauterine growth retardation.