The paper considers the possible mechanism of the pathogenesis of COVID-19 caused by SARS-COV-2, associated with damage to red blood cells, which the authors attribute to the main key target that triggers a cascade of reactions leading to multiple organ failure. The paper presents morphological evidence for the presence of pathological forms of erythrocytes characteristic of various anemias in the blood vessels and parenchyma of damaged lungs of patients with COVID-19. The death of red blood cells leads to cell ischemia and anemia. The defeat of brain neurons, blood vessels and hematotissue barriers in organ systems is a consequence of ischemia due to the impossibility of transferring hemoglobin by damaged erythrocytes and ends at the terminal stages of the development of the disease with their dysfunction. Adaptive erythropoiesis with an increase in erythropoietin secretion is especially dangerous for patients suffering from hypertension, and then it is impossible, since all organs involved in the synthesis of erythropoietin are damaged. In this case, the synthesis of hemoglobin is also disrupted due to a deficiency of iron and cyancobolamin, whereas toxic iron and hemosiderin are deposited in the tissues. K E y w o r d s-COVID-19, SARS-COV-2, erythrocytes, hemoglobin, erythropoiesis, viruses, pathogenesis of COVID-19.
Одним из основных требований к разработке экспериментальных моделей цереброваскулярных заболеваний является их максимальная приближенность к реальной клинической практике. В работе систематизированы данные по основным методам моделирования острой ишемии головного мозга (ОИГМ), представлена их классификация, анализируются данные о преимуществах и недостатках той или иной модели. Обсуждаются результаты экспериментальных исследований по изучению патогенеза ОИГМ с использованием различных моделей (полной и неполной глобальной, локальной и мультифокальной ишемии) и способов их реализации (перевязка артерий, клипирование, коагуляция, эмболизация и др.). Особое внимание уделяется «стабильности» последствий острого нарушения мозгового кровообращения: необратимых ишемических повреждений головного мозга или обратимых с реперфузией заданной продолжительности. Отмечается, что важное значение в этих исследованиях должно принадлежать современным методам прижизненной визуализации очагов острого ишемического повреждения, что позволяет оценивать динамику патологического процесса. Предлагаемый метод отвечает требованиям гуманного обращения с животными. Подчеркивается, что выбор релевантной модели ОИГМ определяется задачами предстоящего исследования и технологическими ресурсами научной лаборатории. Development of experimental models for acute forms of cerebrovascular diseases is essential for implementation of methods for their prevention and treatment. One of the principal requirements to such models is their maximum approximation to actual clinical practice. This review systematized major models of acute cerebral ischemia (ACI), their classification, and presented information about their advantages and shortcomings. Also, the review presented results of experimental studies on pathophysiological mechanisms of different types of modeled ACI (complete and incomplete global, local, and multifocal ischemia) and methods for creating these models (arterial ligation, clipping, coagulation, embolization, etc.). Particular attention was paid to “stability” of the consequences of acutely impaired cerebral circulation - an irreversible ischemic brain injury or a reversible injury with reperfusion of a given duration. The authors emphasized that in such studies, a special significance should be given to intravital imaging of acute ischemic damage foci using modern methods, which allow assessing the dynamics of the pathological process and meet the requirements to humane treatment of animals. The choice of a relevant ACI model is determined by objectives of the planned study and the technological resources available at the research laboratory.
Red bone marrow samples investigation in deceased COVID-19 patients enabled to identify the phenomena of secondary hemophagocytosis. Analysis of the data showed that phagocytic reactions during infection of patients with SARS-CoV-2 are manifested both in relation to erythrocytes and leukocytes. The data obtained make it possible to expand the strategy of therapeutic measures, taking into account the new data on the mechanisms of the pathogenesis of COVID-19 in severe viral infection based on morphological findings and additional information on the involvement of young erythrocytes and lymphocytes in the structure of the red bone marrow in the cascade of pathological reactions. The results obtained confirm a wide range of aggressive damaging effects of SARS-CoV-2 in the development of multiple organ failure against the background of COVID-19 and the involvement of the red bone marrow in the pathological process. The authors supplemented information about the mechanisms of hypoxia in COVID-19, which is not only a consequence of damage to the respiratory epithelium, but also the result of damage to erythrocyte differons both at the level of red bone marrow and in peripheral blood. This fact must be taken into account in the development of a treatment strategy and in the creation of new drugs for the treatment of infected patients with various strains of SARS-CoV-2.
Despite the fact that HPV infection is widespread among the population around the world, more than 150 strains of HPV viruses are known. At the present stage it is still unclear, why HPV-associated oral papillomas in dental patients either spontaneously undergo involution or become malignant. We investigated the quantitative dynamics of Langerhans cells depending on localization in the structure of such papillomas: in the peripapillary space, in the tissue of the oral mucosa in the presence of HPV infection, without a clinical picture of papillomas and in healthy tissue. It has been established that with long-term existing papillomas, antigen presentation is disturbed, and Langerhans cells can be an indicator of papilloma malignancy.
Development of methods for targeted treatment aimed at inhibiting angiogenesis in malignant tissues is of great importance for modern oncology. The features of expression of CD34-positive cells at the border of the tumor and malignant tissue were studied. High expression of CD34-positive cells in small and large vessels during malignancy and is in correlation with the size of the tumor and the age of the disease. A promising target for targeted treatment is VEGF, as the main regulator of angiogenesis during tissue malignancy.
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