The article presents analyzis of the data of the clinical course of Covid-19 and probable pathogenetic mechanisms of lesions, which are presented in foreign and domestic literature. The hypothesis about the hematotoxic effect of the SARS-CoV-2 virus is considered, which may cause its multi-system action. An analogy is made of the pathogenesis of multiple organ lesions in case of viral infection and in acute poisoning with hemolytic poisons and iron preparations, in which the development of metabolic acidosis, toxic hemolysis, and an increase in free hemoglobin and iron ions in the blood plasma are the central link. The article proposes to use a set of diagnostic measures aimed at confirming the hematotoxic component during SARS-CoV-2 infection and methods for assessing the severity of the condition, adopted in clinical toxicology.Taking into account the experience of treating acute poisoning with hemolytic poisons, attention is focused on the importance of using alkalizing therapy in order to remove the products of hemoglobin breakdown and prevent acute nephritic failure. When confirming the presence of a toxic factor, methods aimed at eliminating toxic products of hemolysis can be used – antidote therapy and methods of surgical detoxification. This complex of therapeutic measures in clinical toxicology is effective, aimed at the prevention of acute renal failure and toxic coagulopathy. The authors believe that the hypothesis of a hematotoxic factor in the pathogenesis of Covid-19 requires a targeted therapeutic strategy and targeted study.
В России острые отравления этанолом являются серьезной проблемой практического здравоохранения. Это обусловлено как числом больных с острыми отравлениями, так и сохраняющейся высокой летальностью, составляющей до 60% от всех смертельных отравлений [1, 2]. Более того, до 25% пациентов от всех поступающих в стационар экстренной помощи страдают в той или иной степени алкогольной зависимостью [3], а каждый 7-й случай смерти в общесоматическом стационаре обусловлен последствиями злоупотребления алкоголем [4].
Relevance. The pathogenesis of COVID-19 remains one of the most pressing. The literature discusses the role of iron as a factor supporting inflammatory processes, hypercoagulability and microcirculation crisis in severe COVID-19.The aim of study. was to identify changes in iron metabolism in patients with severe COVID-19 and hyperferritinemia.Material and methods. In this study, we used a content analysis of available scientific publications and our own observations of the peculiarities of the clinical picture and laboratory parameters in patients with a severe course of COVID-19 who had hyperferretinemia at the height of the disease. The main group consisted of 30 patients hospitalized in the Department of Anesthesiology, Resuscitation and Intensive Care of N.A. Semashko City clinical Hospital No. 38 with the diagnosis COVID-19, bilateral polysegmental pneumonia, severe course and hyperferritinemia. The diagnosis of a new coronavirus infection was confirmed by visualization of bilateral viral lung lesions with chest CT-scan, positive PCR test for SARS-CoV-2 and the presence of immunoglobulins to SARS-CoV-2. The control group consisted of 20 healthy volunteers. The study evaluated the biochemical parameters of iron metabolism, fibrinolysis and markers of inflammation. Changes associated with impaired iron metabolism were assessed by the level of serum iron, transferrin, daily and induced iron excretion in the urine. Statistical processing was carried out using nonparametric methods.Results. All patients with severe COVID-19 and hyperferritinemia showed signs of impaired iron metabolism, inflammation and fibrinolysis — a decrease in the level of transferrin (p<0.001), serum iron (p><0.005), albumin (p><0.001), lymphocytes (p><0.001) and an increase in leukocytes (p><0.001), neutrophils (p><0.001), CRP (p><0.005), IL-6 (p><0.001), D-dimer (p><0.005), daily urinary iron excretion (p><0.005) and induced urinary iron excretion (p><0.001). Conclusions The study showed that in the pathogenesis of the severe course of COVID-19, there is a violation of iron metabolism and the presence of a free iron fraction. The appearance of free iron can be caused by damage to cells with the “release” of iron from cytochromes, myoglobin, hemoglobin, or violation of the binding of iron to transferrin, which may be the result of a change in the protein structure or violation of the oxidation of iron to the trivalent state. When assessing the degree of viral effect on the body, one should take into account the effect of various regulators of iron metabolism, as well as an assessment of the level of free iron not associated with transferrin. Keywords: new coronavirus infection, COVID-19, SARS-CoV-2, iron metabolism, free iron, ferritin, transferrin, NTBI, nontransferrin bound iron>˂0.001), serum iron (p˂0.005), albumin (p˂0.001), lymphocytes (p˂0.001) and an increase in leukocytes (p˂0.001), neutrophils (p˂0.001), CRP (p˂0.005), IL-6 (p˂0.001), D-dimer (p˂0.005), daily urinary iron excretion (p˂0.005) and induced urinary iron excretion (p˂0.001).Conclusions. The study showed that in the pathogenesis of the severe course of COVID-19, there is a violation of iron metabolism and the presence of a free iron fraction. The appearance of free iron can be caused by damage to cells with the “release” of iron from cytochromes, myoglobin, hemoglobin, or violation of the binding of iron to transferrin, which may be the result of a change in the protein structure or violation of the oxidation of iron to the trivalent state. When assessing the degree of viral effect on the body, one should take into account the effect of various regulators of iron metabolism, as well as an assessment of the level of free iron not associated with transferrin.
This review is focused on the substrate antihypoxant reamberin used in intensive therapy of acute poisoning with special reference to the mechanisms of its action consisting in the reduction of the severity of metabolic disorders manifested as a decrease of tissue hypoxia, recovery of antioxidant defense and suppression of the activity of lipid peroxidation and endotoxicosis. The antihyhypoxant activity of reamberin is apparent as the reduction of the hypoxic brain lesions in patients with acute poisoning which leads to a significant improvement in the clinical course of acute poisoning and decreases the number of adverse outcomes.
РеЗюМеВ статье представлены результаты многоцентрового, рандомизированного, двойного слепого, плацебо-контролируемого клинического исследования эффективности и безопасности препарата инозина глицил-цистеинил-глутамат динатрия (Моликсан®) в терапии острых тяжелых отравлений этанолом. ЦеЛь ИССЛеДОВАНИЯОценка эффективности и безопасности применения препарата инозина глицил-цистеинил-глутамат динатрия в новом режиме дозировании в терапии тяжелых отравлений этанолом. МАТеРИАЛ И МеТОДыМатериал исследования -данные 133 пациентов с тяжелым отравлением этанолом. Критерии включения: возраст от 18 до 60 лет, кома 1-2-й ст. (14-27 баллов по шкале комы Глазго-Питтсбург -ШКГП), содержание этанола в крови более 2,5‰. Пациенты рандомизированы на две группы: группа «Исследуемый препарат» (группа «ИП») -67 пациентов, которым дополнительно к стандартной терапии вводили исследуемый препарат -инозина глицил-цистеинил-глутамат динатрия в дозе 3,0 мг/кг; группа «Плацебо» -66 пациентов, которым дополнительно к стандартной терапии вводили 0,9% раствор натрия хлорида в дозе 3,0 мг/кг. Сравнительный межгрупповой и внутригрупповой анализ проводили по основным клиническим, лабораторным показателям и данным электроэнцефалографического (ЭЭГ-) мониторинга. РеЗУЛьТАТыИсследование показало положительное влияние исследуемого препарата -отмечено статистически значимое сокращение периода комы с 137 (75;180) до 78 (50;155) минут (р<0,001), зафиксированы статистически значимые более высокие значения ШКГП через 3 и 6 часов от начала терапии (р<0,01), сокращение времени формирования ЭЭГ-паттернов пробуждения у пациентов с «дельта-комой » с 192,2 (161,9; 222,5) до 112,5 (97,6; 127,6) минут (p<0,001); снижение частоты сердечных сокращений (р<0,02), снижение количества жалоб на слабость и головокружение (р<0,005), у пациентов с высоким уровнем в крови аланинаминотрансферазы (АлТ) снизилась частота развития и выраженность тремора (р<0,01). Выявлено статистически значимое гепатопротекторное действие препарата, которое проявилось снижением уровня АлТ (р<0,001), аспартатаминотрансферазы (р<0,001) и прямого билирубина (р<0,03); влиянием препарата на метаболические процессы -снижение уровня в крови лактата (р<0,02), повышение BE-ECF (р<0,01), уровня в крови глюкозы (р<0,01) через 3 часа после введения препарата и калия через 24 часа (р<0,03). Анализ данных безопасности не выявил статистически значимых различий между группами лечения, серьезных нежелательных явлений не зафиксировано.
To evaluate the influence of the degree of obesity and high-volume liposuction on body composition, hemodynamic, blood oxygen. The actual values of the cardiac index and stroke index, as well as the calculation of these indicators on a body surface area of the "ideal subject" showed a significant correlation with body mass index, which confirms the impact of obesity on hemodynamic changes, myocardial dysfunction and the development of severe arterial hypoxemia. Analysis of the parameters of liquid sectors body showed insufficient increase in total, extracellular fluid and blood volume by a significant rise of fat and muscle mass. It is believed that the increase in blood volume in obesity is adaptive in nature and occurs in response to expansion of the vascular bed with increasing body weight. After liposuction large volume of significant hemodynamic changes were not obtained. In the late period against reduction in fat mass oxygenizing improved lung function. Carrying a large volume liposuction are not adversely impact on the reserve possibilities myocardial hemodynamics in the long term. Timely diagnosis of adaptive changes in hemodynamics and fluid sectors organism, which can be considered as prognostic risk factors must be considered when choosing the volume lipoaspiration.
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