Research of <i>PNPLA3</i> I148M Gene Polymorphism in Patients with Non-Alcoholic Fatty Liver Disease, with Liver Cirrhosis and with Hepatocellular Carcinoma

Aim: to determine the frequency of PNPLA3 rs738409 C&gt;G gene polymorphism, leading to p.I148M substitution, in patients with non-alcoholic fatty liver disease (NAFLD), and to reveal the association between polymorphism and probable NAFLD outcomes: liver cirrhosis (LC) and hepatocellular carcinoma (HCC).Materials and methods. The study was conducted according to the “case-control” design, three main groups were formed: a group with NAFLD (n = 46), a group with LC (n = 61), a group with HCC (n = 50), as well as a control group (n = 70), for all groups we performed genotyping of the rs738409 polymorphism of the PNPLA3 gene. The relationship between the occurrence of different genotype variants and the diagnosis of patients was evaluated, the odds ratio (OR) of progression of NAFLD and the reliability of intergroup differences were determined.Results. NAFLD patients with PNPLA3 I148M polymorphism have a significantly higher chance of developing LC and HCC. The odds ratio for the GG genotype was 7.94 (95 % Cl: 2.19–28.84; p = 0.030) for LC and 6.51 (95 % Cl: 1.15–4.08; p = 0.039) — for HCC with concomitant LC. The presence of the minor G allele also increases the likelhood of transition from NAFLD to LC (OR = 2.38; 95 % Cl: 1.41–4.02; p = 0.010) and HCC in the presence of cirrhosis (OR = 2.17; 95 % Cl: 1.15–4.08; p = 0.039). Differences in the frequency of PNPLA3 polymorphism between the NAFLD and HCC groups were not significant. Additional risk factors for HCC associated with NAFLD are overweight (OR = 5.14; 95 % Cl: 1.94–13.67; p &lt; 0.001), arterial hypertension (OR = 8.49; 95 % Cl: 3.05–23,62; p &lt; 0.001) and diabetes mellitus (OR = 8.57; 95 % Cl: 1.03–71.48; p = 0.032).Conclusion. The frequency of single nucleotide polymorphism PNPLA3 significantly differs in patients with NAFLD, cirrhosis and HCC compared with the control group of healthy volunteers. The PNPLA3 I148M polymorphism increases the incidence of NAFLD progression to cirrhosis and HCC, but only with concomitant cirrhosis

Risk Factors for Obesity Development in Different Periods of Childhood

Obesity is an important health problem in many countries. Obesity among the child population is growing steadily, including the Russian Federation. Development of this disease often occurs in childhood and sometimes the origin of obesity goes back to prenatal period. There are a number of endogenous and exogenous factors than play an important role in development of obesity. These are heredity, socioeconomic status of the family, factors which are revealed during pregnancy and child delivery — weight gain, administration of antibacterial drugs and hyperglycemia in mother during her pregnancy, mode of delivery, feeding type and time of complementary food introduction, excessive consumption of calories with food, improper daily routine and lack of sleep, skipping meals, use of gadgets and associated physical inactivity and excessive food intake, marketing of high-calorie foods and others. Prevailing risk factors can be identified for each age period. Study and early identification of risk factors taking into account age of a child is necessary to take timely prevention measures and inform parents and their children about possible reasons and consequences of obesity

Characteristics of blood pressure level in children with different body weight

BACKGROUND: Essential arterial hypertension (AH) develops more often in children with accompanying risk factors — obesity, overweight, positive heredity and genetic predisposition.AIM: Study of peculiarities of arterial hypertension clinical course in adolescents with normal body weight, overweight and obesity.MATERIALS AND METHODS: The study was conducted on children with arterial hypertension who received treatment in two hospitals in Voronezh in 2016–2020. A retrospective analysis of the children’s case histories was carried out taking into account the anamnesis, clinical laboratory and instrumental examination data and the pharmacotherapy. Some children underwent polymerase chain reaction genetic testing to determine pathological alleles of genes regulating blood pressure (BP).RESULTS: 96 patients aged 9 to 17 took part in the study. The group with normal body weight included 38 children (39.6%), median age 16.4 (aged 10.7; 17.9), with overweight — 33 people (34.4%), median age 15.2 (aged 12.0; 17.9), with obesity — 25 children (26.0%), median age 14.5 (aged 9.2; 17.9). Obese children developed arterial hypertension at earlier age (p = 0.023). According to blood pressure daily monitoring (BPDM), pathological values of systolic blood pressure (SBP) during the day (above the 95th percentile) among children with normal body weight were observed in 17 patients (44.7%), with excess body weight — in 14 people (42.4%), with obesity — in 16 people (64%), p = 0.031. Accurate difference values between the groups were obtained in terms of time index (TI) of SBP at night (p = 0.006). Time index of diastolic BP during the day &gt; 50% was observed only in the obese children group — 4 people (16%) (p = 0.042). Pathological alleles of the angiotensinogen gene (AGT: 704 T&gt;C), aldosterone synthase gene (CYP11B2: -344 C&gt;T) and endothelial nitrogen synthase type 3 (NOS3: -786 T&gt; C) were identified most frequently during genetic testing in some patients.CONCLUSION: Children with obesity developed earlier arterial hypertension compared to the same-age children with normal body weight and more often had unfavorable type of arterial hypertension according to BPDM. These results can be used to choose individual therapy and to develop special attention as regards certain target organs damage

Diet peculiarities of organized preschoolers living in families with different material well-being status

The family well-being can affect the approaches to the organization of the child’s nutrition and its future health. The aim of this study was to evaluate the style and quality of diet among children ages 3 to 7 years in families with different financial status according to the parents’ self-assessment. The cross-section study included 190 organized preschool children that were divided into the 2 groups. The first group included 83 children with a sufficient family income; the 2nd group included 107 children with an insufficient level of family income. We revealed that the children in families with higher social and financial status consumed the fruits 1.5 times more often and had the defects of diet 2 times less than children with lower economic status. At the same time all children not enough eat fish, meat, vegetables, cereals, fruits.Уровень материального благополучия семьи может оказать влияние на организацию питания ребенка в домашних условиях и в дальнейшем отразиться на формировании пищевого поведения ребенка. Цель работы — оценить режим и качество рациона питания организованных детей в возрасте от 3 до 7 лет в условиях семей с различным социально-экономическим статусом. Проведено кросс-секционное исследование, в которое было включено 190 организованных детей дошкольного возраста, 1-ю группу составили 83 ребенка с достаточным уровнем материального положения семьи, 2-ю группу — 107 детей с недостаточным уровнем семейного дохода. Было выявлено, что в группе детей из семей с достаточным уровнем материального положения доля использования в рационе питания фруктов была в 1,5 раза выше (р = 0,02), а число дефектов режима питания было в 2 раза меньше (р = 0,0003), чем у детей с недостаточным уровнем семейного дохода. При этом все обследованные дети дошкольного возраста недостаточно употребляли в пищу рыбу, мясо, овощи, крупяные продукты, фрукты

Major and minor lymphocytes subpopulations in peripheral blood and cerebrospinal fluid of children with meningitis

Introduction. The analysis of current publications indicates at our insufficient understanding of subpopulation composition of lymphocytes in peripheral blood and cerebrospinal fluid (CSF) during pediatric neuroinfectious diseases. It has been found that the main lymphocyte populations are divided into many small (minor) subpopulations.The purpose of this research was to assess percentage of major and minor blood and CSF lymphocyte subsets in children with aseptic viral meningitis (AM) or bacterial purulent meningitis (BM).Materials and methods. Phenotyping of blood and CSF lymphocytes of children aged from 4 months to 17 years diagnosed with AM (n = 86) and BM (n = 39) was carried out by using flow cytometry. As a comparison group, we analyzed peripheral blood and CSF samples collected from children with acute respiratory viral infections (ARVIs) associated with syndrome of meningism (n = 27). There was evaluated percentage of the major cell subpopulations (CD3+ T-lymphocytes, T-helpers — CD3+CD4+ Th, cytotoxic T-lymphocytes — CD3+CD8+ CTL, natural killer cells — CD3-CD16+CD56+ NK, B-cells — CD3-CD19+), as well as minor lymphocyte subsets (double positive (DP) (CD3+CD4+CD8+), double negative (DN) (CD3+CD4-CD8-) T-cells, NKT (CD3+CD16+CD56+), CD3-CD8+ NK, CD3+CD8dim and CD3+CD8 8bright).Results. It was found that the acute period of BM and AM vs. the comparison group (ARVI) was characterized by significant differences in the blood and CSF composition of major and minor lymphocyte subsets. In particular, blood T-cells, Th, CTL, NK, NKT, DN, CD3-CD8+ NK, CD3+CD8bright and CD3+CD8dim dominated in parallel with significantly lowered B-cell frequency in AM vs. BM. In the CSF of children with AM, T-cells and Th prevailed, whereas count of B-cells and CD3-CD8+ NK was lower compared to those in BM. In addition, further differences were revealed in CSF and blood cell subset composition depending on nosological entity, while maintaining differences in some major and minor lymphocyte subpopulations lacked in the comparison group. Calculating the CSF/blood ratio for the major and minor lymphocyte subsets uncovered the prevalence for the majority of cell subpopulations (the coefficients ranged from 1.2 to 16.4) in the CSF of the comparison group (ARVI), except B-cells, NK and CD3-CD8+ NK (coefficients ranged from 0.07 to 0.31). AM and BM were featured with various changes in the CSF/blood ratio found for most of the studied subpopulations in the acute period as well as the recovery phase highlighted with characteristic traits for each nosological form.Conclusion. The data obtained indicate about finding specific features in the activation of systemic and intrathecal immune response during viral and bacterial meningitis in children, which may be used as an additional differential diagnostic criterion

ОСОБЕННОСТИ ТЕЧЕНИЯ И ИСХОДЫ НЕОНАТАЛЬНЫХ ГЕПАТИТОВ РАЗЛИЧНОЙ ЭТИОЛОГИИ

We have performed primary examination of 50 children with neonatal hepatitis. Prevalence of herpes infection as the etiologic agent (40,0%) has been found, as well as parenteral hepatitis, both as an isolated (26,0%) and mixed infections. We conducted a comparative analysis of clinical and laboratory data at initial examination and determined the outcomes of neonatal hepatitis to 12 months of life depending on the etiology. Congenital CMV- etiology hepatitis characterized by more cytolysis, mainly due to aspartate aminotransferase and cholestasis, which is 33,3% of cases combined by acholia and urobiliya. In 50,0% of patients with CMV-hepatitis was detected fibrosis with a mean value of liver elastography 9,9 kPa, which is ІІІ degrees of fibrosis METAVIR scale, whereas in children with primary chronic hepatitis C and concomitant HCV + DNA-virus infection fibrosis was not registered. Despite on the large number of modern non-invasive techniques for determining the degree of hepatic fibrosis, the use of its in children during the first months of life is limited and does not allow to predict disease outcome.Проведен анализ клинико-лабораторных данных 50 пациентов с неонатальным гепатитом в динамике с целью определения особенностей течения болезни и ее исхода к 12 месяцам жизни в зависимости от этиологии и первичных клинико-анамнестических данных заболевания. Выявлено преобладание герпетической инфекции в качестве этиологического агента (40,0%), а также парентеральных гепатитов как в виде изолированной HCV-инфекции (26,0%), так и смешанной HCV+ДНК-инфекции. Установлено, что врожденные гепатиты CMV-этиологии протекают более тяжело с выраженным цитолизом (преимущественно за счет аспартатаминотрансферазы) и холестазом, который в 33,3% случаев сопровождается ахолией и уробилией. У 50,0% пациентов с CMV-гепатитом выявлен фиброз со средним значением эластографии печени 9,9 кПа по шкале METAVIR, тогда как у детей с первично-хроническим гепатитом С и сочетанной HCV+ДНК-вирусной инфекцией фиброз зарегистрирован не был. Несмотря на наличие большого количества современных неинвазивных методик по определению степени фиброза печени, использование их у детей первых месяцев жизни ограничено и не позволяет прогнозировать исход заболевания

Синдром системного воспаления в патогенезе респираторно-синцитиальной вирусной инфекции

The aim of the study was to obtain new biochemical data on the pathogenesis of respiratory syncytial viral infection (RSVI) in children.Object and methods: 60 children aged 1 month to 5 years, treated in the clinic of Pediatric Research and Clinical Center for Infectious Diseases, from which in 50 patients RNA RSV was isolated in smears from the oropharynx. The comparison group consisted of 10 children who failed to verify RSVI by laboratory methods. All children at admission and before discharge from the hospital (after-7-9 days) underwent a clinical blood test a Sysmex XP-300 hematology analyzer (Japan). Alpha-1-antitrypsin and alpha-2-macroglobulin were determined in blood serum by quantitative immunoturbidimetry on a biochemical analyzer CLIMA-15 (Spain) using Sentinel test systems (Italy). Determination of the amount of total protein, albumin and C-reactive protein in serum was carried out on an automatic analyzer Taurus (Instrumentation Laboratory, Italy) using reagents of the company «Vector-best» (Russia). The study of protein fractions in blood serum was carried out by capillary electrophoresis on the device Minicap company Sebia (France) with the help of test systems «Minicap Protein(e) 6» of the same manufacturer. The levels of cytokines (IL-6, IL-10) in serum were determined by ELISA on ELISA analyzer «INFINITI» (TECAN, Austria) using reagents firm «Vector-best» (Russia).Results: RSVI occurs with lesions of the lower respiratory tract in 42% of cases, with the development of complications in 44% of sick children. The study revealed a prolonged increase in serum alpha-2 fraction of globulins, immunoregulatory cytokines with pro-inflammatory (IL-6) and anti-inflammatory (IL-10) action and, which may indicate the presence of subacute inflammatory process associated with the persistence of RS-virus. Lower levels of gamma-globulin fraction, including the main specific and nonspecific immunoglobulins, in children with PCR-proven RSVI, both in the acute period and in the period of convalescence, probably can cause repeated RSV-diseases, as well as an increase in the risk of atopic diseases.Conclusion. The long-term increase in the level of subacute inflammation markers, established in the course of the study, even against the relieve of clinical picture of the disease, makes the question of developing an etiopathogenetic treatment of respiratory syncytial viral infection with the use of drugs with antiviral and anti-inflammatory action relevant.Цель: получение новых клинико-биохимических данных о патогенезе респираторно-синцитиальной вирусной инфекции у детей.Материалы и методы: 60 детей в возрасте от 1 месяца до 5 лет, получавших лечение в клинике Детского научно-клинического центра инфекционных болезней, из которых у 50 человек в мазках из ротоглотки выделена РНК РСВ. Группу сравнения составили 10 детей, у которых респираторно-синцитиальная вирусная инфекция не верифицирована лабораторными методами. Всем детям при поступлении и перед выпиской из стационара проведен клинический анализ крови на гематологическом анализаторе Sysmex XP-300 (Япония). В сыворотке крови методом количественной иммунотурбидиметрии на биохимическом анализаторе CLIMA-15 (Испания) с использованием тест-систем фирмы Sentinel (Италия) определяли альфа-1антитрипсин и альфа-2-макроглобулин. Определение количества общего белка, альбумина и С-реактивного белка в сыворотке крови проводили на автоматическом анализаторе Taurus (Instrumentation Laboratory, Италия) с применением реагентов фирмы «Вектор-Бест» (Россия). Исследование белковых фракций в сыворотке крови осуществляли методом капиллярного электрофореза на приборе Minicap фирмы Sebia (Франция) с помощью тест-систем «Minicap Protein(е) 6» той же фирмы-изготовителя. Уровень цитокинов (ИЛ-6, ИЛ-10) в сыворотке крови определяли методом твердофазного иммуноферментного анализа на иммуноферментном анализаторе «INFINITI» (TECAN, Австрия) с использованием реагентов фирмы «Вектор-Бест» (Россия). Результаты: респираторно-синцитиальная вирусная инфекция протекает с поражением нижних дыхательных путей в 42% случаев, с развитием осложнений – у 44% больных детей. Установлено пролонгированное увеличение в сыворотке крови альфа-2 фракции глобулинов, иммунорегуляторных цитокинов, обладающих провоспалительным (ИЛ-6) и противовоспалительным (ИЛ-10) действием, что может свидетельствовать о наличии подострого воспалительного процесса, ассоциированного с персистенцией РС-вируса. Более низкий уровень гамма-глобулиновой фракции, включающей основные специфические и неспецифические иммуноглобулины, у детей с доказанной методом ПЦР респираторно-синцитиальной вирусной инфекцией, как в остром периоде, так и в периоде реконвалесценции, вероятно, может обусловливать повторные заболевания респираторно-синцитиальной вирусной инфекцией, а также увеличение риска развития атопических заболеваний. Заключение. Установленное в ходе исследования длительное повышение уровня маркеров подострого воспаления даже на фоне купированной клинической картины заболевания делает актуальным вопрос разработки этипатогенетического лечения респираторно-синцитиальной вирусной инфекции с применением препаратов с противовирусным и противовоспалительным действием.