Subjects of research: 40 patients with acute viral hepatitis В (AVHB) and 120 patients with chronic viral hepatitis В (CVHB)
Purpose of work: Study clinical and pathogenic significance of allergic reactions of various types in transition of VHB in lingering andchronic course
Methods of research: Clinical, laboratory, allcrgologic, immunologic, statistical. The results obtained and their novelty: Allergic hereditary family diseases. Allergy to antibiotics and insects bites occur more frequently in patients with A VHB. Unlike patients with AVHB and other forms of CVHB patients with high activity of CVHB more frequently suffer from food allergy and infectious and allergic diseases. Clinical manifestations of allergy dominated among patients with high activity of CVHB. Allergic reactions of the 1st type (anaphylactic type) developed chiefly in patients with AVHB, reactions of the Ilnd (cytotoxic reactions), Hird (Artus phenomenon) and IVth (reaction of delayed type) types were typical for patients with CVHB. Pathogenic importance of the allergic reactions of the Ilnd, Illrd and IVth types in forming of lingering course of the disease. Kctotifcn was effective in complex treatment of patients with AVHB and CVHB with high activity of pathological process in liver.
Practical value: Detection of markers of the Ilnd (index of neutrophils damage), Illrd (circulating immune complexes) and IVth (reaction of inhibition of leukocytes migration) can be considered as prognostic criterion for transition of VHB into lingering course. It is expedient to include ketotifen, preparation exerting a direct antiallergic and mediated hcpatoprotective effects, in the treatment of patients with AVHB and high activity of CVHB.
Degree of embed and economic effectivity: Obtained results were introduced in the clinic of Research Institute of epidemiology, microbiology and infectious diseases, Republican children hospital for infectious diseases of Karakalpakstan and in the course of studies of Tashkent Medical Academy and Nucus branch of Tashkent pediatric medical institute. . Methodical appliance on the thesis data "Viral hepatitis B, D, C and E" and information letter were published (Nucus, 2005) and sent to the corresponding institutions. Economical efficiency for 1 patient amounts to 5000 sum. Sphere of usage? medicine
Fied of application: Infectious hospitals, medical departments in villages, family polyclinics.
Sabjects of research: AR patients, 161 - DNA samples of patients, also from healthy donors, polymorphism in GSTT1 genes, GSTM1, TNF-a, RANTES and CTLA4.
Purpose of work: To study the clinical and genetic features of manifestation of allergic rhinitis in view of studying the influence of the polymorphic markers of key genes involved in its formation, the frequency of occurrence and risk factors for disease, new approaches and forecasting of complex treatment of this disease.
Methods of research: clinical-laboratory, immunoenzyme method and molecular genetic (PCR etc.), statistical.
The results obtained and their novelty: first described the clinical and molecular genetic parallels AR. A comparative analysis ofpathogcnctically important for the formation of atopy gene polymorphisms TNF-a, RANTES, CTLA4, GSTT1 and GSTM1, among apparently healthy donors and patients with RA of various origins. For the first time revealed significant association of polymorphisms 308G> A TNF-a gene with the development of seasonal forms of AR and RANTES gene polymorphism A403G with the development of year-round form of the form AR. Set associative connection is not enough pronounced polymorphism 49A / Ggcnc CTLA4, and GSTT1 null genotype and GSTM1 genes individually with the development of AR. For the first time set key intcrgenic interactions that determine the risk of developing RA with high probability.
Practical value: The obtained results complement the global database of molecular genetics of AR, as well as serve as a basis for the creation and implementation of special prevention programs.
Degree of embed and economic effectivity: developed results arc used in clinical practice of the Republican scientific center of the specialized allergy, ENT Department Clinic TMA-2 and in the laboratory of Medical Genetics, Research Institute of Hematology and Blood Transfusion, Ministry of Health Uzbekistan.
Field of application: medicine.
Subject of research: 117 patients, of them 28 were without allergy; 77 ones with allergic background and without allergy to basic plastic, 12 patients with allergy to acrylic plastic.
Purpose of work: To undertake a clinical and immunologic study and on its basis to develop approaches for predicting allergic effects of basic plastics on oral mucosa in patients with allergic background.
Methods of research: clinical, stomatoscopical, microbiological, immunologic and cytochemical.
The results obtained and their novelty: It is demonstrated that in patients with allergic background (AB) the frequency of development of allergic response (AR) to plastics of a dental prosthesis (PDP) has made 13.48%. AR to PDP in the oral mucosa (OM) manifests itself in the form of hyperemia, edema, presence of teeth prints, disturbance in epithelium transparence in the form of opacification with elements of keratosis, various coatings, catarrhal events, hyperemia of glands and decubital stomatites. On the background of development of AR to PDP, enhancement of local immunity of OM, augmentation of T-LP, IRI rise, aggravation B-lymphopenia, rising in IL-4, IgE and IgG, a high NP activity in NBT-test were noted. The rise in NBT-test rates by over 15% at in vitro monomer affect prior to prosthetic repair was associated with development of allergic response following prosthetic repair.
Practical value: Introduction of prediction of risk of development of the allergic response based on NBT-test rates into orthopedic stomatology will enable to optimize selection of basic materials for patients with allergic background, to lower economic and moral damage caused by it.
Degree of embed and economic effectivity: The results of the research are used in medical practice of an orthopedic stomatologic out-patient department of the Third Clinic of the Tashkent Medical Academy and in the educational process oat the faculty of orthopedic stomatology and orthodontology of the Tashkent Medical Academy.
Field of application: stomatology.
Relevance and necessity of the subject of the dissertation. Today parenteral viral hepatitis is steel one of biggest problems because of its abundance among population, high risk of liver cirrhosis and hepatocellular carcinoma. As well as development of extrahepatic manifestations, which is causing diagnostic and treatment problems in patients with chronicle viral hepatitis (CVH). According WHO approximately 1/3 of worldwide population is infected by hepatitis В virus (HBV). Annually about 2 mln. people dies from HBV complications 700 000 from liver cirrhosis and 300 000 from hepatocellular carcinoma. In addition, more than 500 mln. people are infected by hepatitis C virus (HCV) infection and in fact there is pandemia which is 5 times more than AIDS. 60% of HCV infected patients after acuity developing chronicle disease. Near 20% of HCV infected patients develop progressing fibrosis and cirrhosis. Approximately 20-90% of these patients (with cirrhosis) pass away (dying) from hepatocellular carcinoma in 5 years. WHO is prognosis further grows of global HBV and HCV infection incidence1.
The existence of a broad spectrum of antibodies against the hosts body's own tissues for various non-infective and infective diseases have already installed a number of studies. The cause of autoantibodies is considered to be the loss of the body tolerance to "their" own antigens, and the presence of these autoantibodies can largely determine the outcome of the pathological process. It is known that different antibodies against its own tissues in low titers present in 10% of the normal human population and are transient, as markers of tissue damage resulting from the most varied effects. As trigger autoimmune disorders can act genetic, viral, drug and hormonal factors, acting both alone and in combination with each other. After termination of such exposure and removal from the body of destroyed tissue formation of autoantibodies may stop, but can be saved by specifying an adverse outcome of the pathological process.
Thus, the high incidence of CVH in the country, the systemic nature of lesions, late diagnostics of autoimmune disorders in such cases, resulting in a reduction of quality of life of patients with CVH, an increase in direct costs of treatment, determine a serious economic and social importance of the problem for the health of each state that substantiates the relevance of studying the theoretical and practical issues of CVH, in general, and autoimmune disorders in them, in particular.
The aim of the research: is to study of immunopathogenic mechanisms of formation and development of autoimmune disorders through complex study of factors of the virus and the host, various links of immunity, interferon and cytokine status in patients with chronic viral hepatitis В and C
The scientific novelty of the dissertational research:
For the first time conducted a screening study of patients with chronic viral hepatitis В and C in order to identify systemic and tissue autoantibodies;
First defined the characteristics of particular factors of the virus and the body at chronicle hepatitis В and C, with and without systemic and tissue autoantibodies, their influence on the development of autoimmune disorders;
Identified pathogenetic significance of the relationship processes between autoimmunity and phenotypic features of immune cells in the course of a comprehensive study of the immune system with the analysis of humoral, cellular and non-specific immunity in patients with chronic viral hepatitis based on clinical and laboratory, virological and biochemical parameters;
Revealed a correlation with a number of key cytokines of clinical and laboratory syndrome and immune system performance, depending on the detection system and tissue autoantibodies;
First presented a comprehensive assessment of the cytokine and interferon profile of blood serum in HVG with and without systemic and tissue autoantibodies set features production of pro- and anti-inflammatory cytokines, interferons and their pathogenetic role in chronic viral hepatitis with autoimmune disorders;
The informative and diagnostic significance of clinical, laboratory and immunological parameters and their integral characteristics at CVH different etiology;
Algorithm of immunoassay for the detection of patients with chronic viral hepatitis autoimmune disorders and systemic nature of the tissue and identified additional immunological criteria for diagnosis and prognosis of the disease course in the development of autoimmune disorders.
CONCLUSION
1. Conduct a screening study in patients with chronic viral hepatitis В and C, identified system (organonespetsificheskie) autoantibodies in 43.8% and 30.2%, respectively, and tissue (organ-specific) autoantibodies in 61.4% and 73.5% of cases respectively.
2. It is established that the HBV more frequently than in HCV detected narrow (single) range of SAT (in 87.2% and 62.3%, respectively) And a (complex) spectrum CAT 3 times more often detected by HCV than with HBV (in 3737% and 12.8%, respectively). In the presence of TAT, high levels of autoantibodies against endocrine organs identified and HBV and HCV. Higher rates of TAT to the liver, kidney, small intestine and skin marked with the HBV and to the synovium of joints in the HCV.
3. The relationships detect SAT and TAT on the factors of the virus: the HCV non-replicative form (identification CAT 2 times more often) with genotype 2 HCV-infection (CAT 1.4 times TAT 2.4 times more likely) and mutant (HBeAg-negative) strains of HBV-infection (CAT 2.4 times, 1.6 times TAT often) and at high rates of viral load detection SAT and TAT significantly higher.
4. Determine the relationship identifying SAT and TAT on the factors of the body when HBV Mostly young age 18-35 years (72.5% of all cases with the SAT, 70% of all cases with TAT), female sex (62.5% vs. 44, 4% in the group without SAT, 53.3% versus 26.3% in the group without TAT), low to moderate biochemical activity often accompany the SAT detection by biochemical indicators are prevalence of cytolytic syndrome with symptoms of fibrosis.
5. Determine the relationship identifying SAT and TAT on the factors in the organism HCV: predominant age of 36-50 years (46.3% of all cases with TAT), the normal biochemical parameters revealed in the group with SAT 1.64 times times more likely (27 3%) than in the group without SAT, biochemical indicators are prevalence of mesenchymal-inflammatory and cholestatic syndromes with symptoms of fibrosis.
6. Established that the HBV pathogenetic basis of autoimmune disorders systemic nature is to stimulate the production of antibodies by B-lymphocytes, and decreased elimination of the pathogen, with mild antiviral response. When HCV autoimmune disorders systemic nature developed on the background of profound T-cell immunodeficiency and pronounced anti-viral response with sufficient elimination of the pathogen.
7. It is shown that the immune status of patients with chronic hepatitis C is characterized by a decrease in the absolute number of basic lymphocyte subpopulations (especially constant and deep - CD8 + - and CD 16 + -cells). The observed lymphocytosis (relative) was due to the high content of CD20 + -lymphocytes. The contents of all studied cell immunoreactivity and IgA, IgG, IgM, CEC, with reduced - leukocytes, CD3 + CD4 + CD8 + -, CD 16 + - cells, CIC, raised - Lymphocytes (%) IgM, IgG; other indicators vary in different directions. These changes characterize the adaptive orientation of structural and functional disorders and, in this case reflect the predominance of Th2 response of Thl.
8. The changes at the level of intermolecular regulation of HVG with an autoimmune component characterized by severe symptoms doimmunnogo inflammation due to lower activity of regulatory T cells, which correlate with the degree of activity and clinical manifestations of chronic viral hepatitis and indicate possible pathogenetic and clinical role of autoimmune disorders systemic nature of viral diseases liver.
9. Develop integrated indicators counting severity of autoimmunity to every single organ or tissue, as well as to the general tissue autoimmune status.
10. An increase the number of links between the various indicators while reducing their total information content, the weak integration of many individual immunological parameters among themselves and with other system parameters, indicating discoordination immunoregulatory mechanisms in chronic hepatitis, more pronounced in the presence of autoimmune disorders.
The urgency and relevance of the dissertation topic. In the past decades, according to WHO, the number of people with pancreatitis has doubled, and the average age of patients has decreased from 50 to 38 years. Throughout the world there has been a steady trend towards an increase in the number of diseases of the gastrointestinal tract.
The aim of the research work is to study the immunogcnctic mechanisms of the formation of various clinical forms of HP and to justify their role in optimizing early diagnosis and treatment.
Scientific novelty of the research work is as follows: for the first time, a comprehensive study of patients with CP in Uzbekistan was conducted and marked dysfunction of immunogenctic mechanisms for the formation and development of disorders leading to or contributing to the risk of the disease; correlations of key cytokines with a number of clinical laboratory syndromes and indices of the immune system in alcoholic and biliary CP; the use of cytokine profile indices for differential diagnosis of severity and clinical forms of CP has been proposed; established dysfunction of the cytokine cascade gene, which causes the expression of various key mediators of inflammation and contributes to destructive inflammatory changes in the pancreas; pathogenetically significant interrelationships of genetic variants of polymorphism with clinical laboratory indicators in CP and their role in the development of complications arc determined; the use of cytokine status indicators as a prognostication of the severe course of chronic pancreatitis and its complications is pathogenetically substantiated; a new direction in the treatment of pancreatitis has been developed - a combined approach to the complex of therapeutic measures in CP.