Farida M. Khamidova

The study of chronic inflammation of lung tissue in bronchiectasis in children is necessary for a deeper understanding of the cellular and molecular mechanisms of chronic respiratory diseases and the development of new approaches to their treatment. The aim of the study was to investigate histological and immunohistochemical changes in the structures of the bronchi and lungs in bronchiectasis in children. The study used lobes or fragments of lungs removed during surgery for bronchiectasis in 62 children. The obtained micro-preparations of bronchial and lung tissue were stained with haematoxylin and eosin, picrofuchsin according to Van Gieson, and resorcinol fuchsin according to Weigert. Immunohistochemical studies of lung micro-preparations were performed using monoclonal antibodies to Ki-67, Bcl-2, CD3, and CD20. Comparing the results of immunohistochemical studies in children with bronchiectasis and in the control group, significant differences can be noted. Thus, the level of CD3+ cells, a marker of immune activity, is significantly higher in children with bronchiectasis in all age groups compared to control indicators (p<0.001) and continues to increase with age. Similarly, the content of CD20+ cells is also higher in children with bronchiectasis regardless of age (p<0.05 and p<0.01), with a tendency for their number to increase with age. The Bcl-2 indicator, associated with cell apoptosis processes, is slightly elevated in children with bronchiectasis, but the differences are not always statistically significant. At the same time, the Ki-67 level, which reflects the intensity of cell proliferation, is significantly higher in children with bronchiectasis in all age groups compared to the control group (p<0.001). Thus, children with bronchiectasis show changes in immunohistochemical characteristics, indicating activation of the immune system and increased cell proliferation. These processes may be associated with inflammation and immune responses typical of this disease. Consequently, it can be concluded that all links of the immune system are activated in children with bronchiectasis. At the same time, it has been established that destructive changes in immune components prevail in children with bronchiectasis, which indicates a decrease in their protective function.

Despite already existing algorithms for diagnosis and treatment, pneumonia remains one of the leading causes of childhood death under 5 years of age worldwide. The concept of pathological changes occurring on its basis, such as immune response and morphofunctional changes may open new possibilities to avoid lethality from this disease. The aim of this study was to investigate changes in the components of pulmonary immunity in pneumonia in young children taking into account modern data on innate and adaptive defence mechanisms, immunohistochemical markers of inflammation and peculiarities of cellular response to infectious agents. Morphometric and immunohistochemical study of 41 children aged from 0 to 18 months who died of pneumonia was carried out. The study of lungs in children of different ages with inflammatory diseases of respiratory organs allowed to reveal the following morphofunctional features of the structures of innate and acquired immunity. In children who died of pneumonia at the age of 0-7 days, the height of epithelium in large and medium bronchi does not change compared to the control group. However, in children who died at the age of 8-28 days, there is a sharp increase in the height of the epithelium, and this increase is more pronounced in large and small bronchi. The own lamina beneath the multiple ciliated epithelium is also strongly increased, especially in large bronchi. From 1 month to 6 months of age, the level of bronchial epithelium height in the lungs of sick children increases significantly in bronchi of all calibres, including small bronchi. Apparently, the increase in epithelium thickness in small bronchi reflects the severe course of the disease. In children at all age groups with inflammatory diseases in the lungs, the percentage of lymphocytes in the respiratory sections is significantly higher than in the control group. The highest values of the percentage of lymphocytes were found in children aged 1-3 months. Immunohistochemical analysis showed that children with pneumonia of different ages have activation of T-lymphocytes (CD3) and B-lymphocytes (CD20). At the same time, the level of anti-apoptotic factor Bcl-2 is reduced, indicating the presence of apoptosis in lymphocytes. The percentage of Ki-67 associated with proliferation is also reduced, indicating a decrease in the proliferative activity of lymphocytes. Thus, in the development of innate and acquired immunity in children who died of pneumonia, there is a dissociation in the proliferative activity of bronchial epitheliocytes of different diameters. Although the number of lymphoid cells in the lungs of these children increases, but apparently to an insufficient degree, as they have a decrease in anti-apoptotic factor and proliferation index.

Relevance. Cystic fibrosis (CF), also known as mucoviscidosis or Landsteiner-Fanconi disease, is an autosomal recessive hereditary disorder characterized by systemic damage to the exocrine glands. It manifests as pathological mucus secretion, leading to chronic inflammation and dysfunction of the respiratory, digestive, and reproductive systems. Among all forms of the disease, the intestinal form is the most common, particularly in newborns, making it essential to study its prevalence, immunohistological features, and genetic predisposition. The aim of the research is to investigate the epidemiology and genetic aspects of cystic fibrosis. Results. Analysis of various screening programs indicates that the most effective methods combine biochemical analysis (IRT) with molecular testing (CFTR variant panels). However, the effectiveness of newborn screening (NBS) depends on establishing optimal IRT threshold values, expanding genetic testing panels to account for ethnic specificity, and implementing repeat testing to reduce the proportion of false-negative cases. Conclusion. This review examines current research on the implementation of screening programs, the sensitivity and specificity of tests, and the clinical significance of identified CRMS/CFSPID cases.

Relevance: The purpose of choosing this topic is related to the need to study the cellular structures of the respiratory epithelium. The mucous membrane of the respiratory tract consists of a complex system of cells that perform protective functions. The sources contain studies on the microscopic structure of the epithelial lining of the trachea and age-related features of the transport function, but there is little information about the epithelial layer of the bronchi. The purpose of the study is to study the morphological structure of the bronchial wall of deceased patients without respiratory system diseases. Materials and methods. In 2020-2024, a complex histological and histochemical examination of bronchial wall fragments and lung tissue sections of 26 deceased individuals aged 45 to 70 years without respiratory system diseases was conducted at the Department of Pathological Anatomy of the Multidisciplinary Clinic of Samarkand State Medical University. Research results: The muscular layer of the mucous membrane of the wall of the large-caliber bronchi consists of 3-5 rows of smooth muscle cells, which have a weak basophilic nucleus and eosinophilic cytoplasm. The submucosal layer of the bronchi consists of bundles of connective tissue fibers and hyaline cartilage, there are hyaline cartilage plates that are interconnected by thin connective tissue fibers, which in turn form a fibrous cartilage layer. Conclusion. Data obtained as a result of histological and histochemical examination of fragments of bronchial walls and lung tissue taken as samples from deceased adult patients without respiratory system diseases.

Relevance. Chronic hyperplastic laryngitis (CHL) is one of the most common pathologies of the larynx, affecting up to 10% of patients with ENT diseases. In 5% of cases, it precedes the development of laryngeal cancer, making early diagnosis and timely treatment critical criteria for preventing malignant transformation of tissues. The main risk factors for CHL have been described, including smoking, alcohol consumption, exposure to carcinogenic substances, and chronic inflammatory processes of the upper respiratory tract. A review of modern diagnostic methods for laryngopharyngeal reflux (LPR), such as 24-hour pH monitoring, multichannel impedance analysis, and salivary pepsin testing, has been conducted. Data on the impact of LPR on vocal function, including increased acoustic and aerodynamic disturbances in patients with chronic inflammatory laryngeal diseases, are presented. The aim of the study is to investigate the influence of laryngopharyngeal reflux (LPR) on the development of chronic hyperplastic laryngitis (CHL) and precancerous conditions of the larynx, as well as to evaluate modern methods of diagnosis and treatment of this pathology. Results of the study. Chronic hyperplastic laryngitis (CHL) is a pathological process characterized by hyperplasia of the laryngeal mucosa and changes in its structure, creating favorable conditions for tissue malignancy. Conclusion. Modern diagnostic methods (pH-impedance monitoring, pepsin analysis, videolaryngostroboscopy) play a key role in identifying LPR, but there is still no single gold standard for diagnosis, which complicates the diagnosis and choice of treatment strategy.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are now uncovering new possibilities in the field of internal medicine owing to their diverse protective effects. In the second part of the literature review, we explore potential applications of SGLT2i in hepatology, neurology, ophthalmology, and oncology, mechanisms of action of such drugs as dapagliflozin, empagliflozin, canagliflozin, etc, and their effect on different organs and systems.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a revolutionary class of drugs with far-reaching protective effects in multiple organs. The protective potential of SGLT2i is much broader than that of the classical concept of glucose control and consists of an entire conglomerate of associated pleiotropic effects. This study aims to provide a descriptive review of the pleiotropic therapeutic potential of SGLT2i. The first part of the literature review examined the use of SGLT2i in cardiology and nephrology. The use of SGLT2i represents an innovative approach to improving patients’ quality of life and course of heart failure and chronic kidney disease, regardless of left ventricular ejection fraction and type 2 diabetes.

Background: Data published by task groups of the Ministry of Health of the Russian Federation, the European Society of Cardiology, and other medical associations and institutions show that chemotherapy-induced cardiomyopathy is still a challenging issue that requires further research.Objective: To compare the cardioprotective potential of trimetazidine and dapagliflozin in a rat model of doxorubicin-cyclophospha-mide cardiomyopathy.Materials and methods: Our randomized in vivo experimental study included 80 Wistar female rats. Doxorubicin and cyclophosphamide were administered at a dose of 15 mg/kg and 150 mg/kg, respectively. Trimetazidine (42 mg/kg) and dapagliflozin (14 mg/kg) were additionally administered to groups 3 and 4, respectively. The total duration of the experiment was 14 days.Results: Doxorubicin+cyclophosphamide mode of chemotherapy induces the development of toxic-ischemic cardiomyopathy. The trimetazidine and dapagliflozin administration was accompanied by stabilization of cardiovascular parameters. Comparison of both drugs’ cardioprotective properties revealed a clear advantage of dapagliflozin over trimetazidine, especially in terms of such an important indicator as N-terminal pro-B-type natriuretic peptide.Conclusions: Further research aimed at exploring the cardioprotective potential of dapagliflozin against cardiovascular complications of chemotherapy is justified from a pathogenetic point of view.