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.
Purulent-inflammatory diseases of the maxillofacial region in young children is becoming more and more important. The urgency of the problem is determined not only by the frequency of non-odontogenic inflammatory diseases in children, but also by changes in the clinical course of sluggishly current processes in recent years due to the somatic status of the body. In this regard, it became necessary to study the characteristics of the course of various purulent processes in the maxillofacial region in children combined with anemia. As you know, the hemostasis system actively reacts to various exogenous and endogenous influences, in particular to purulent-inflammatory processes.
Несмотря на значительные успехи стоматологии, число больных с одонтогенными воспалительными заболеваниями не имеет тенценции к уменьшению. За последние 10 лет в Республике Узбекистан число воспалительных заболеваний периапикальных тканей зубов возросло на 7-8%. Воспалительные заболевания челюстно-лицевой области занимают довольно большой удельный вес и составляют около 25-30% всех стоматологичеких заболеваний. В абсолютном большинстве случаев (90-96%) этиологическим фактором воспалительных заболеваний челюстно-лицевой области является одонтогенная инфекция
Проблема гнойной инфекции в челюстно-лицевой хирургии была и остается актуальной, что объясняется ростом числа больных с воспалительными процессами челюстно-лицевой области, увеличением числа случаев тяжелого генерализированного течения инфекций. Несмотря на широкое внедрение в клиническую практику таких методов лечения, как местное и общее хирургическое пособие, применение антибактериальных препаратов и химиотерапевтических средств, дезинтоксикационной и корригирующей терапии, терапии сопутствующих заболеваний, современных физиотерапевтических средств, воспалительные заболевания челюстно-лицевой области продолжают представлять угрозу для здоровья и жизни человека.
The combined injuries of maxillofacial region make up special place among the bones and tissues of the human body as a result of its functional and cosmetic importance. Soft tissue wounds of the maxillofacial injuries have number of distinguishing features that differs from traumas of the other parts of the organism. In this article the number of information given about physical, chemical features of the ozone and its influence for the healing of the combined soft tissue wounds of the maxillofacial injuries.
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.