The purpose of the study is to determine the significance of genetic factors in the development of chronic nephritic syndrome in children and to clarify the features of the clinical course
The оbject of research were 129 children aged 4-15 years who were treated for chronic nephritis in the nephrology department of the Samarkand Regional Multidisciplinary Paediatric Medical Centre.
The scientific novelty of the study is as follows:it has been established that the severity of chronic nephritic syndrome in children is associated with clinical manifestations (gradual development, dyspepsia, abdominal pain) and an increase in the amount of Cystatin C in the blood;for the first time, it was revealed that the development of sclerotic lesions due to increased proliferation in patients with the presence of the MMP-9 (A-8202G) rs 11697325 genotypes in chronic nephritic syndrome leads to a worsening of the clinical course of the disease; established early diagnostic marker MMP-9 (A-8202G) rs 11697325 and its tissue inhibitor TIMP-2 (C536T) rs 11551797 in chronic nephritic syndrome in children in the diagnosis of the disease; for the first time, the prognostic value of the alleles of the MMP-9 (A-8202G) rs 11697325 genes and the homozygous G/G genotype in determining the risk of developing the disease in children with chronic nephritic syndrome has been proven.
Implementation of the research results. Based on scientific results of evaluation of the role of polymorphic genes of matrix metalloproteinase and its tissue inhibitors in chronic nephritic syndrome in children: methodological recommendation “The role of polymorphic genes of matrix metalloproteinase and its genetic inhibitors in the development of chronic nephritic syndrome in children” was developed and approved (reference of the Ministry of Health of the Republic of Uzbekistan No. 8n-r / 554 of 30.02.2022).
This methodological recommendation made it possible to predict the development of chronic nephritic syndrome in children and improve preventive measures; approved and developed on the basis of scientific results of research on early diagnosis and prognosis of chronic nephritic syndrome “Dynamics of clinical and laboratory parameters in nephritic syndrome in children”, (reference of the Ministry of Health of the Republic of Uzbekistan No. 8n-r / 555 of 30.02.2022).
This methodological recommendation made it possible to optimize the diagnosis and treatment tactics for various forms of nephritic syndrome in children;
The results obtained were implemented in the practice of health care, in particular, in the Republican Children's National Medical Center, in the 1st clinic of the Samarkand State Medical University, in the Samarkand Regional Children's Multidisciplinary Medical Center (conclusion No. 8 n-r/324 of 21.06.2022 of the Ministry of Health of Uzbekistan).
The application of the obtained results to practice has made it possible to reduce the frequency of recurrence of the disease in children, prevent complications of the disease, improve the quality of life of patients, diagnose and prevent the disease.
The structure and scope of the dissertation. The dissertation consists of an introduction, 4 chapters, conclusions, practical recommendations. The volume of the dissertation is 120 pages.
Topicality and demand of the subject of dissertation. Bronchial asthma (BA) is one of the most common and serious diseases, which in the world suffer from 3 to 12% of the child population of the globe. Proportion of adolescents with asthma, is one third of all children with this disease. High prevalence of asthma in the numbers of teenagers, characteristics of the disease, age-related aspects of the functioning of the endocrine and immune systems of teenagers that cause difficulties which arise in the course of the diagnostic process, highlight the need to find innovative approaches to diagnosis and treatment of this disease.
It is known that the key immune mechanisms in the pathogenesis of the vast majority of AD cases is real and indisputable fact. Currently, considerable interest to researchers involved in the pathogenesis of positions of allergic diseases, especially asthma, along with IL-4 and IL-13 causes a number of other (IL-6, IL-8, IL-10, IL-5, INF-a and INF-y) immunoregulatory cytokines.
Genetic predisposition plays an important role in the development of allergic diseases. Currently available data on the relationship with asthma and associated with disease symptoms polymorphism approximately 150 genes. Important role as the main contender for the predisposition to asthma gene is a gene encoding flchain of high affinity receptor IgE. Interaction elevated levels of antigen-specific IgE with FceRip plays a central role in the pathogenesis of allergic asthma. Particularly attractive candidate gene asthma is also one of the enzyme genes biotransformation - GSTirl, encoding glutathione S-transferase and л1 express almost exclusively in the pulmonary tissue. This gene is located at the locus 11 ql 3, for which repeatedly shown clutch with atopic symptoms. Accumulated in the literature say about the relationship of gene polymorphism FceRI, GSTnl with different allergic diseases.
From this perspective, the study of immunological and genetic mechanisms of the pathogenesis of this disease for the construction of rational treatment and prevention emphasizes the relevance of this thesis research.
From the earliest days of independence, the country has successfully implemented state programs aimed at reforming the health care system. As a result, the targeted implementation of organizational health and research activities aimed at effective diagnosis, prevention and treatment of asthma among adolescents, with some success in the treatment of this disease in the country. However, now the problem of early diagnosis and the development of effective programs for treatment and prevention among adolescents with asthma remain one of the most important issues of modern health care. This research work was carried out in the framework of the tasks set by the Resolution of the Cabinet of Ministers of the Republic of Uzbekistan "On additional measures to improve the health of women and the younger generation," dated 25.01.2002 for the №32. In this regard, the need to deepen the information received about the state of cellular and humoral immunity among adolescents, asking pathogenetic informative immunogcnctic studies in asthma arc one of the important criteria demand the dissertation topic.
Purpose of research is study the immunological and genetic mechanisms of the pathogenesis of asthma in adolescents and form the basis of this plan rational diagnostic and therapeutic measures in this pathology.
In To achieve this goal the following tasks of research is solved:
to establish the clinical course of asthma in the population of adolescents living in the Samarkand region, in the early stages of the pathological process in the bronchopulmonary system.
explore the features of the state of cellular and humoral immunity, as well as activation markers in asthma in adolescence by determining the immunophenotype of lymphocytes in the peripheral blood.
to examine the level of production of immunorcgulatory cytokine interleukin-6 and interfcron-y and install them pathogenetic informative in asthma among adolescents.
to determine the features of distribution of allele and genotype frequencies of polymorphic variants of genes and FceRip GSTnl population Uzbek people with asthma, compared with the healthy part of the population.
examine the clinical and immunological aspects effectiveness of therapies using drugs and polioksidony tsikloferon in patients with asthma in adolescence.
on the basis of studies to develop a multivariate model of formation of bronchial asthma and develop an optimal algorithm for the diagnosis, treatment, prevention in adolescents with this pathological condition.
Scientific novelty of dissertational research consists in the following:
proposed introduction to the work of doctors teen clinics layered approach testing can significantly improve the detection rate of asthma in adolescence and optimize treatment and preventive measures in high-risk groups;
first defined the peculiar characteristics of the quantitative parameters of the immune status of patients with asthma in the cohort of adolescence and the corresponding proposed regulations and guidance documents for the healthy part of the adolescent population;
for the first time presents a comprehensive assessment of the cytokine profile of blood serum in bronchial asthma in adolescents. Specific features of products immunorcgulatory cytokines IL-6 and INF-y and their pathogenetic and regulatory information content in asthma among adolescents;
first analyzed the distribution of alleles and genotypes of polymorphic gene variants and gene FceRip GSTirl among patients with different phenotypic variants of AD and healthy individuals of Uzbek nationality, which resulted in the identified markers of increased risk or, conversely, resistance to the development of asthma in adolescents Uzbek ethnicity;
algorithms for phase diagnosis, treatment and prevention of asthma in adolescence in terms of disclosure of important moments of the pathogenesis of the disease, allowing to build a rational sequence of diagnostic search, aimed at verifying the diagnosis and expedient construction of preventive measures.
Conclusion
1. Set the frequency of occurrence of the disease and the structure of "asthma" in the arid zone among teens. Said pathology is recorded in 9,6% of the population surveyed adolescents, while the disease is more common among females. In the structure of the disease prevails periodical exposure and mild persistent form.
2. Identified by clinical features of asthma among adolescents living in the arid zone, indicate a high frequency of lesions of the bronchial tree association with allergic processes in other organs and tissues: in 73,9% of the AR, 53,7% with AK. 16,6% with BA and 14% with urticaria/angiocdcma.
3. Found that in the study population of patients with asthma adolescence occur expressed disturbances of the immune status, manifested deficit indicators as cell (CD3‘, CD4+, CD8 , CD16+), and humoral immunity (CD19 , IgA, IgG, IgM) and activation markers (CD23+, CD95). The immune status of patients with asthma in young people, adolescence has distinctive features, the depth of detected violations immunoreactivity was most pronounced in the younger age group.
4. In patients with bronchial asthma in adolescence revealed distinct changes in cell-cell interactions in the immune system: a significant increase in the content of Th2-cclls secreted IL-6 is a regulator of maturation of antibodies and immunoglobulin production itself, and vice versa reducing regulator activity of Th 1-cell cytokine INF-y.
5. It was found that the contents of cytokines IL-6, INF-y and in the peripheral blood is in communication with one pathogenic disease. It is shown that the lowest level of INF-y production in the scrum is characteristic of allergic clinical pathogenic variant asthma in adolescence. Adolescents suffering from predominantly infectious form of asthma, there is a sharp trend towards increased production of IL-6 in peripheral blood.
6. Revealed that markers of increased risk of allergic forms of asthma in adolescents Uzbek ethnicity arc genotype FceRip-109T/T allele FceRip-109T, low-risk markers - FcsRip-109C/C and allele Fc£Rip-109C. A high degree of cohesion genotype FcsRip-109T/T allele and FcsRip-109T with hereditary burden of asthma in the Uzbek population.
7. Among females ethnic Uzbek Association revealed lie-105 allele and genotype Ilc-105/Ilc-105 polymorphic gene locus GSTkI at high risk for asthma. Revealed that the genotype associated with the development Ilc-105/Ilc-105 allergic form of asthma in adolescents Uzbek population.
8. Complex therapy with adolescents’ patients with asthma ciklofcron and polyoxidonium, providing immunocorrective effect, enhances the clinical efficacy of basic therapy. In the study of prophylactic efficacy of immunomodulators positive indicators prevailed in the group of patients receiving polioksidony, necessitating its inclusion in the priority scheme of integrated treatment and prevention of asthma in adolescents.
The aim of the study is to development of an algorithm for managing pregnancy and childbirth by studying the functional state of the mother-placenta-fetus system in pregnant women who have undergone COVID-19 in different trimesters of pregnancy.
The object of the study was 105 pregnant women who, were treated at the Samarkand Regional Perinatal Center and a specialized maternity center for pregnant women with COVID-19
Тhe scientific novelty of the research consists of the followings: for the first time in pregnant women infected with COVID-19, a relationship was established between the course of pregnancy, childbirth, the postpartum period and the development of complications depending on the trimester and severity of the disease; a direct correlation has been established between the state of the vessels of the mother-placenta-fetus system (resistance and pulsation indices, Endothelin-1 indicators), disorders in the hemostasis system (D-dimer, platelet aggregation) and the clinical course of the disease in pregnant women who underwent COVID-19; it has been established for the first time that the developed scale for assessing risk factors for non-developing pregnancy in women infected with COVID-19 (age, BMI, obstetric history, gestation period, hemostasis system status, endothelial function and severity of the disease) can serve as a prognostic marker of the degree of risk of pregnancy complications; it was proved for the first time that the choice of effective therapy for restoring hemodynamics in the mother-placenta-fetus system, in women who underwent COVID-19 at different stages of pregnancy, leads to a decrease in the number of thrombophilic complications.
Implementation of the research results. The results of the scientific research were introduced into the practical activities of the Samarkand Regional Perinatal Center by Order No. 128/1 of 01.09.2022 and the Samarkand City Maternity Complex No. 1 by order No. 58/1 of 03.10.2022. In pregnant women who underwent COVID-19 at different periods of pregnancy, changes in the mother-placenta-fetus system were determined using simple and effective research methods, such as ultrasound and Dopplerography, and this saved 53,000 soums; obstetricians and gynecologists, as well as neonatologists and therapists, are needed to diagnose signs of complications in the echocartin, that is, it has been proven that there is no need for other highly qualified specialists for this, due to the lack of need to train new personnel, state budget funds have been saved. With early detection of disorders in the hemostasis system in pregnant women with COVID-19: the period of stay of patients in the hospital was reduced from 10.5 days to 7.5 days and the number of hospital bed days was reduced; due to the reduction of the period of stay in the hospital for several days, the number of necessary drugs was reduced (on average, drugs are used for 1 day in the amount of 130,000 soums). Examination of pregnant women infected with viral diseases using simple and effective research methods such as ultrasound and Dopplerography served to save 85,000 soums: in the early stages up to 16 (10-11 weeks. - fetometry), 19-21, 32-34, 38-40 weeks of pregnancy; due to the absence of the need to use other research methods, it was possible to reduce costs by 23.5%; early detection of changes in the hemostasis system and endothelial dysfunction using fast, budgetary and effective research methods, contributed to the prevention of possible pregnancy complications, as well as the absence of the need to use long-term and expensive research methods, and this saved 106 000 soums: the coagulogram was checked in 105 (100%) patients, time was saved and efficiency was increased; endothelin-1 was also determined in 105 (100%) patients, efficiency was increased by 78.6%.
Improving the functionality of blood circulation in the uteroplacental and fetal-placental systems, a comprehensive analysis of possible complications during pregnancy and childbirth in women who have had viral infections, improving diagnostic, preventive and prognostic measures for managing pregnancy and childbirth contributed to the birth of live, full-term and healthy newborns in women who experienced COVID-19 during pregnancy, as well as a decrease in maternal mortality and perinatal mortality, 43% of women underwent rehabilitation in the postpartum period, 23.8% of women who underwent severe COVID-19 improved their quality of life.
To introduce scientific novelty on the topic “The impact of COVID-19 on the state of hemodynamics in the mother-placenta-fetus system in pregnant women”, a letter was sent to the Ministry of Health from Samarkand State Medical University on November 9, 2022 under No. 4295 (Conclusion of the Ministry of Health No. 8 n-z / 679 of December 15, 2022).
The structure and volume of the dissertation. The content of the dissertation consists of an introduction, five chapters, conclusion, list of used references. The volume of the dissertation consists of 113 pages.
По данным Всемирной организации здравоохранения, в последние годы наблюдается рост заболеваемости острой респираторной вирусной инфекцией. В связи с этим внимание педиатров и отоларингологов привлекают острые стенозирующие ларинготрахеиты (ОСЛТ). Согласно данным многолетних исследований, число пациентов с ОСЛТ колеблется от 0,1 до 0,4% от всех госпитализированных в стационар детей с диагнозом «острая респираторная вирусная инфекция». Развитие стенозирующего ларинготрахеита при острой респираторной вирусной инфекции (ОРВИ) резко отягощает состояние больных детей, а порой от присоединения его к основному заболеванию зависит жизнь ребенка.
С первых дней независимости в нашей стране с целью повышения качества медицинской помощи населению последовательно реализуются широкомасштабные реформы. Так, эффективное медицинское обслуживание детей обеспечило своевременное выявление, раннюю диагностику и лечение больных с ОСЛТ, что позволило на 3-4 дня сократить сроки лечения их в стационаре.
Несмотря на многочисленные научные исследования, посвященные изучению закономерностей инфекционного процесса при стенозирующем ларинготрахеите, роли дисбиоцсноза слизистых оболочек верхних дыхательных путей, процесс эндогенной интоксикации (ЭИ), развивающийся в результате болезни детей и его связь с течением заболевания, а также состояние системы местного и общего иммунитета диктуют необходимость совершенствования методов их коррекции в свете современных требований. Вместе с тем, причины рецидивирования острых стенозирующих ларинготрахеитов до конца не определены, важной задачей представляется разработка прогностических критериев оценки исходов ОСЛТ.
Данное диссертационное исследование в определенной степени служит решению задач, предусмотренных в постановлениях Президента Республики Узбекистан № ПП-2133 от 19 февраля 2014 года «О Государственной программе «Год здорового ребенка» и № ПП-2221 от 1 августа 2014 года "О Государственной программе по дальнейшему укреплению репродуктивного здоровья населения, охране здоровья матерей, детей и подростков в Узбекистане на период 2014-2018 годы», а также в других нормативноправовых документах, принятых в данной сфере.
Научные исследования, направленные на совершенствование методов комплексной диагностики, лечения и профилактики стенозирующих ларинготрахеитов у детей проводились во многих ведущих медицинских центрах, таких как детский медицинский центр Шнайдера (Израиль), Университетская клиника Гиссена (Германия), Детская клиника Святой Марии (Германия), Центр инновационной медицины Интербалкан (Греция), клиника Женераль (Швейцария), клиника Роял (Великобритания), Медицинский центр Куинс (Великобритания), клиника ИДИБАПС (Испания), госпиталь Святого Луки (Япония), Федеральный научноклинический центр оториноларингологии ФМБА России (Россия), а также Ташкентский педиатрический медицинский институт и Республиканский специализированный научно-практический медицинский центр педиатрии (Узбекистан).
В результате проведенных исследований были разработаны критерии оценки риска возникновения и рецидивирующего течения ОСЛТ, выявлены механизмы, определяющие чувствительность дыхательных путей (Фрейбург-ская клиника, Германия); установлена эндокринная дисфункция у детей с первичной и рецидивирующей формой острого стенозирующего ларинготрахеита (Детский госпиталь, Ирландия); доказано влияние состава микрофлоры основных локусов организма, соединительнотканной дисплазии, регулирующих систем на функцию внешнего дыхания, формирование пороговой чув-
ствительности и реактивности дыхательных путей у детей с рецидивирующим стенозирующим ларинготрахеитом (РСЛТ) (Мельбурнский университет, Австралия).
В настоящее время в мире целью многих исследований становится дальнейшее определение на иммуномолекулярном уровне роли специфических и неспецифических факторов иммунной защиты в патогенезе острого стенозирующего ларинготрахеита; оценка состояния неспецифической защиты при ОСЛТ; изучение достоверных сдвигов в клеточном звене иммунитета, изменений Т-супрессоров и частично В-лимфоцитов; а также профилактика рецидивов и совершенствование методов диагностики и лечения заболевания.
Как показал анализ специальной литературы, ряд исследователей изучали роль аллергического компонента и вегетативной нервной системы в патогенезе развития первичных и рецидивирующих ОСЛТ. Согласно полученным результатам, более чем у 90% больных детей в патогенезе первичного и рецидивирующего острого стенозирующего ларинготрахеита преобладает аллергический компонент с выявлением общих и аллергенспецифических IgE. Кроме того, доказано, что развитие ОСЛТ при парагриппозной инфекции связано с существенным повышением титра IgE и специфического IgA в назофарингеальных секретах у детей с ОРВИ. Изучены механизмы рециди-вирования ОСЛТ, основанные на значительном изменении иммунологической реактивности организма, которые связаны с его аллергизацией как инфекционными, так и неинфекционными агентами, включая неблагоприятные экологические, сезонные, метеорологические и даже социальные условия. Доказано, что ОСЛТ протекает с вегетативными расстройствами, которые, в свою очередь, оказывают существенное влияние на течение и исход основного заболевания. Предложено усовершенствованное лечение ОСЛТ в разгар заболевания, основанное на применении лекарственных препаратов с учетом типа исходного вегетативного тонуса организма.
Несмотря на многочисленные работы, посвященные изучению острого стенозирующего ларинготрахеита, ее диагностике и методам лечения, тенденция к росту рецидивирования заболевания сохраняется, что диктует необходимость изучения общих закономерностей инфекционного процесса при стенозирующем ларинготрахеите, оценки значения микробиоценоза слизистых оболочек верхних отделов респираторного тракта, нарушений иммунного и интерфероновых статусов и разработки способов их коррекции, прогнозирования заболевания на основе прогностической карты, а также повышения эффективности лечения и профилактических мероприятий.
Бронхиальная астма является наиболее частым воспалительным неинфекционным заболеванием, поражающим дыхательные пути во всем мире. Это обычно связано с сопутствующими состояниями, которые в значительной степени усугубляют его бремя, независимо от того, затрагивают ли они легкие или другие отделы. Самые последние исследования выявили ряд патобиологических взаимодействий между астмой и другими органами с точки зрения общего иммунологического фона, лежащего в основе различных заболеваний. Двузначная связь между астмой и распространенными состояниями, включая сердечно-сосудистые, метаболические или нейродегенеративные заболевания, а также редкие заболевания, такие как серповидно-клеточная анемия, Дефицит α1-антитрипсина и иммунологические состояния с гиперэозинофилией следует учитывать и изучать с точки зрения диагностической работы и долгосрочной оценки пациентов с астмой.
В современном мире, большинство случаев смерти связаны с неинфекционные заболевания (36 миллионов) и чуть более половины из них (17 миллионов) являются в результате сердечно-сосудистых заболеваний; больше одного- треть этих смертей приходится на взрослых людей среднего возраста. В развитые страны, болезни сердца и инсульта являются первым и второй ведущей причиной, смерть для взрослых мужчин и женщины. В связи с широкой распространенностью сердечно - сосудистых заболеваний среди населения планеты, каждый человек должен обращать внимание на факторы, которые подвергают его к заболеванию сердечно-сосудистыми болезнями. Факторы риска представляют собой индивидуальные особенности, оказывающие влияние на вероятность развития в будущем заболевания у конкретного человека.
Интерстициальные заболевания легких (ИЗЛ) у детей раннего возраста часто скрываются под маской пневмонии, бронхиолита, что приводит к поздней диагностике, длительным курсам антибактериальной
терапии и терапии системными стероидами. Для детского ИЗЛ синдрома характерны персистирующее тахипноэ, одышка, кашель, мелкопузырчатые хрипы, гипоксемия, интерстициальные изменения по типу «матового стекла» на КТ легких [1]. Среди детских ИЗЛ особое место занимает заболевание с неустановленной этиологией – нейроэндокринная клеточная гиперплазия младенцев (НЭКГМ). Для этого заболевания характерно сочетание ИЗЛ синдрома и гиперплазии бомбезин-позитивных нейроэндокринных клеток периферических дыхательных путей в биоптате легких [2]. Генетические нарушения метаболизма белков сурфактанта составляют 10% от всех детских ИЗЛ. При наличии мутации генов SFTPC и SFTPА1 респираторных симптомов при рождении может не быть, но позже развивается ИЗЛ, кислородозависимость и необходимость проведения трансплантации легких [3].
In modern society, diseases of the oral cavity are of humanitarian, socio - economic significance. Today, tooth decay and periodontal disease remain the most common dental disease not only among adults, but also among younger populations around the world. According to recent epidemiological studies conducted on healthy children, the incidence of dental pathology is high, with the prevalence of caries among healthy age groups 12-15 years old is 63.3-83 years, 4% and 81.7-88.7%, intensity 3.02 -3.75 and 4.6-5.73, and the prevalence of periodontal tissue diseases in the group of healthy 12- year-old children ranged from 37.8% to 50%, in the 15-year-old group of children it ranged from 57.7% to 84, 7%. The prevalence of caries is also high in children with mental retardation of preschool and school age, while the intensity of caries is higher in children aged 13–18 years with mild mental retardation (MAD). These indicators increase with age and depend on the severity of the underlying disease.
We carried out a program for the prevention of dental diseases in children with disabilities, however, most of them were focused on children with mild and moderate mental retardation, where not only the degree of mental retardation was taken into account, but also teaching them oral care skills, the degree of socialization and the child's diet.