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.
Цель работы. В статье раскрываются перспективы развития бизнеса в реальном секторе экономики в новых кризисных условиях постпандемии. Метод или методология проведения работы. Исследование основывается на общенаучной методологии, которая предусматривает применение системного подхода к решению проблем. В работе использованы методы эмпирического исследования (наблюдение, сравнение, сбор и изучение информации), текущего и перспективного анализа и синтеза теоретического и практического материалов. Основой для проведения исследования послужили труды ученых по вопросам цифровизации экономики и разработки направлений развития предпринимательского сектора в сложных условиях кризиса экономики. Результаты работы. В сложившихся условиях кризиса, вызванного пандемией коронавируса, наиболее пострадавшими признаны предприятия малого и среднего бизнеса, а именно те, кто работает в особо уязвимых отраслях экономики (автоперевозки, воздушный транспорт, туризм, выставочная деятельность, гостиницы, сфера развлечений и досуга, общественное питание, культура и спорт и др). В этой связи в работе делается вывод, что принимаемые Правительством РФ беспрецедентные меры по поддержке предприятий и организаций, функционирующих в особо пострадавших отраслях экономики, следует рассматривать в качестве важнейших и стратегически необходимых инструментов государственной помощи, которые направлены на стабилизацию экономической ситуации в стране в целом, сохранение занятости, недопущение роста безработицы населения, а также финансовую поддержку функционирующих предприятий для выплат заработной платы своим сотрудникам в период кризиса. В работе предложены перспективные направления развития предприятий реального сектора экономики в условиях кризиса. Ключевую роль в дальнейшем развитии должно сыграть массовое внедрение цифровых технологий, а также экосистем их распространения и использования. Благодаря такому воздействию этих передовых технологий предполагается постепенный переход к новой распределительной модели бизнеса в сочетании с развитием роботизации и цифровизации большого количества производственно-хозяйственных процессов, которая позволит «превратить продукты в сервисы» и расширить цепочки создания ценностей, поставок товаров и услуг. Область применения результатов. Результаты исследования могут быть использованы для выстраивания стратегии бизнеса в новых условиях постпандемии. Выводы. Если по максимуму учесть предложенные рекомендации и выстроить стратегию бизнеса, рецессия может стать точкой роста: открываются новые возможности, появляются новые партнеры, высвободившаяся ниша рынка предстает новым направлением развития бизнеса по приемлемой цене и условиям функционирования.
Leukocyte-platelet adhesion during hypoxia, tissue damage, activation of inflammation and coagulation is associated with the expression of ICAM-1 membrane molecules and integrins by blood and tissue cells. At the same time, platelet adhesion receptors determine their adhesion to the endothelium and recruited lymphocytes. The role of platelets in the pathogenesis of ischemic cardiovascular diseases also consists in their ability to modulate both hemostasis and inflammatory reactions, which is accompanied by the secretion of inflammatory mediators and factors that promote the recruitment of leukocytes to tissue damage sites. Purpose of the study: to study the effect of the synthetic glucocorticoid dexamethasone on the expression of adhesion receptors CD18 + and CD54 + on leukocytes, the content of platelets and fibrinogen in the blood of patients with ALLI, the relationship of these indicators with the severity and outcome of the disease. To study the effect of anti-inflammatory therapy, a group of 32 patients treated with dexamethasone was formed; the comparison group was represented by 71 patients with basic therapy, the control group consisted of 15 volunteers. After revascularization, all patients received antiplatelet and anticoagulant therapy. Dexamethasone infusions were carried out in a course of 4 to 6 days after reconstructive surgery. In all patients, the content of C-reactive protein in the blood, the content of platelets and fibrinogen were determined. The number of lymphocytes expressing adhesion molecules ICAM-1 (CD54 + ) and integrins (CD18 + ) was counted using the immunocytochemical method. Studies were performed before surgery and on days 1, 3, 7, and 10 after surgery. With exacerbation of ischemia and damage to the endothelium, the accumulation of cytolysis products, the expression of adhesion molecules increases both on endotheliocytes and on inflammatory effector cells – leukocytes and platelets. Adhesion molecules conduct an activation signal inside the cell, which promotes adhesion of leukocytes and platelets to the endothelium, lymphocytic-platelet adhesion, the formation of a parietal thrombus, and possible occlusion of damaged vessels. Increased expression of adhesion molecules is associated with the activation of metabolism, inflammation, coagulation and oxidative stress, stimulates all hematopoietic lineages, including platelets. The level of involvement of cellular reactions in the pathogenesis of the disease affects the effectiveness and duration of treatment, the risk of recurrent thrombosis and death. Anti-inflammatory therapy with dexamethasone contributed to earlier remission, a decrease in the proportion of infectious complications, such as wound suppuration from 10% to 6%, the number of necessary amputations from 32% to 16%, the frequency of deaths from 31% to 6%, and a reduction in hospital stay from 13 days to 10. Inflammation, adhesiveness of effector cells and thrombosis are important factors in the pathogenesis of acute lower limb ischemia. Therapy with dexamethasone helps to reduce the level of systemic inflammatory response, the number of necessary amputations, the number of complications and adverse outcomes in the treatment of ALLI, and reduce the length of stay in the hospital.
Цель -выяснить влияние терапии дексаметазоном на показатели иммунной реактивности, интенсивность окислительного стресса и деструкции тканей при острой ишемии нижних конечностей, представляющей угрозу потери конечности
To study the pathogenetic and clinical significance of factors of hypoxic brain damage and inflammatory mediators in the development of stroke, to improve the diagnosis using laboratory markers of brain damage and inflammation in patients with acute cerebrovascular accident.We examined 55 people with stroke of the ischemic type at the age of 74 (67; 80) years, the comparison group consisted of 25 volunteers at the age of 65.0 (62.0; 66.5) years. Depending on the outcome of ischemic stroke, patients were assigned to the discharged group or to the deceased group. Blood serum and cerebrospinal fluid (CSF) S100b protein, glial fibrillar acidic protein and interleukin-6 (IL-6); blood serum neurospecific enolase, and cortisol and C-reactive protein (CRP) were determined. Clinical blood test and assessment of fibrinogen content were performed on days 1, 3 and 10 of stroke.There is an increase in the levels of markers of brain tissue damage and systemic inflammation in the blood and CSF in response to cerebral ischemia that reflects the synergy of these pathological processes in patients with stroke, their association with the severity of stroke and its outcome.The results indicate that the postischemic release of neurospecific proteins, an increase in the content of IL-6, CRP, and cortisol make it possible to additionally characterize the severity of stroke and the body's response to damage, and predict the outcome of the disease.Изучение патогенетического и клинического значения факторов гипоксического повреждения мозга и медиаторов воспаления в развитии церебрального инсульта, совершенствование диагностики с использованием лабораторных маркеров повреждения мозга и воспаления у больных с острым нарушением мозгового кровообращения (ОНМК).Обследовали 55 пациентов с ОНМК по ишемическому типу в возрасте 74 (67; 80) лет, группа сравнения — 25 человек без ОНМК в возрасте 65 (62; 66,5) лет. В зависимости от исхода ОНМК были сформированы группы пациентов: выписанные и умершие. Для оценки неврологического статуса пациентов использовали стандартные шкалы и индекс коморбидности. Определяли содержание белка S100b, глиального фибриллярного кислого протеина (ГФКП) и интерлейкина-6 (ИЛ-6) в сыворотке крови и цереброспинальной жидкости (ЦСЖ); нейроспецифической енолазы (НСЕ) и кортизола в сыворотке крови методом иммуноферментного анализа (ИФА), проводился клинический анализ крови, оценивалось содержание фибриногена на 1, 3 и 10-е сутки ОНМК.Увеличение содержания в крови и ЦСЖ маркеров повреждения мозговой ткани и системного воспаления в ответ на ишемию мозга отражает синергию этих патологических процессов у пациентов с ОНМК, их ассоциацию с тяжестью церебрального инсульта и его исходом.Полученные данные свидетельствуют о том, что постишемическое высвобождение нейроспецифических белков, увеличение содержания ИЛ-6, С-реактивного белка (СРБ) и кортизола позволяют дополнительно характеризовать тяжесть церебрального инсульта и реакцию организма на повреждение, прогнозировать исход заболевания.
Aim of investigation. To estimate efficacy and safety of two pharmacological forms of «Phosphogliv» (lyophilizate for intravenous administration and capsules) for the treatment of fatty liver degeneration of non-alcoholic etiology. Material and methods. Original study included overall 180 patients with nonalcoholic fatty liver disease that were randomized to the basic and control groups in the ratio of 2:1. The basic group patients received Phosphogliv 5 mg/day as intravenous bolus injection for 2 weeks, followed by oral intake of 2 capsules t.i.d. for 10 weeks (the total treatment duration was 12 weeks), control group patients received placebo in the same mode. Serum levels of inflammatory marker adiponectin, NAFLD fibrosis score, treatment effect on quality of life and safety of patients were monitored. Results. In 12 wks in patients with more significant cytolysis (threefold and higher serum alanine transaminase activity) and the rate of adiponectin level improvement on the background of Phosphogliv was 57.9% versus only 10.0% (p=0.019) in the placebo group. The mean NAFLD fibrosis score in the basic group remained almost unchanged, while in the control group negative dynamics was revealed, that resulted in statistically significant differences between groups (2.5±1.2 units versus 2.0±1.3 units respectively; р=0.009). At Phosphogliv injection already during the first 2 wks more pronounced improvement of subjective perception of dyspeptic symptoms was observed (mean score was 5.6±1.3 versus 5.1±1.4; р=0.021). When the treatment course was completed the basic group patients had higher mean score by «level of energy» scale (5.9±1.0 versus 5.6±1.0; р=0.034). Only sporadic adverse effects were found to the background of treatment, no statistically significant differences in their rate in were recorded. Dynamics of the basic physical parameters and laboratory tests was comparable as well. Conclusions. Treatment of non-alcoholic fatty liver disease that includes Phosphogliv provides reduction of steatohepatitis activity, retardation of fibrosis progression, improvement of overall disease prognosis and high satisfaction of patients at a favorable safety profile.
To investigate efficacy of early and long term physical training (PT) of moderate intensity in conditions of practical health care in Russia in patients with ischemic heart disease (IHD) of able to work age - survivors of acute coronary events.Three hundred ninety two patients were enrolled in this study. They were randomized into intervention group " O" (n=197) and control group " C" (n=195). Inclusion period was 3- 8 weeks from onset of myocardial infarction (MI), unstable angina (UA), or intervention on coronary arteries. Patients were followed up for 1 year and efficacy of intervention was assessed by results of laboratory (levels of lipids), instrumental (ECG, exercise test on veloergometer, echocardiography), and clinical examination. In the group " O" regimen of PT with work loads of moderate intensity (50-60% of power achieved during exercise test) was used. Duration of FT was 45 - 60 min, frequency - 3 times a week. All patients received standard therapy for IHD and a lipid lowering drug when indicated.Proofs of efficacy of PT in the given contingent of patients were obtained. This was manifested by significant increase of physical working capacity: prolongation of exercise time (+31.7%, p<0.001), increases of volume of work performed (+74.3%, p<0.001) and efficiency of cardiac work according to results of exercise tests. All parameters were significantly different from those in the group " C" . Structural functional parameters of the heart also improved in the group " O" : left ventricular (LV) stroke volume increased 4.5% (p<0.005), ejection fraction increased 7.2% (p<0.001), diastolic LV volume decreased 2.5% (p<0.05), systolic LV volume decreased 8.1% (p<0.001). In the group " C" stroke volume and LV ejection fraction rose to a lesser degree - by 5.5% (p<0.01) and 2.9% (p<0.05), respectively. Differences between groups in dynamics of these parameters turned out to be significant (p<0.05). Moreover in group " C" LV diastolic volume increased 2.3% (p<0.05) and systolic volume did not change, while left atrium increased 3.4% (p<0.002). At intergroup comparison differences in dynamics of these parameters were significant (p<0.005). Analysis of lipid profile after 1 year showed no changes in patients of group " C" , while in group " O" it revealed significant (3.6%) lowering of total (T) cholesterol (CH) (p<0.05 compared with baseline and change in group " C" ) and elevation of high density lipoprotein (HDL) CH (+12.3%, p<0.001; compared with group " C" p<0.005). Atherogeneity index TCH/HDLCH decreased 8.5% in the group " O" (p<0.01), and increased 12% (p<0.02) in the group " C" , difference between groups was statistically significant (p<0.001). In the group " O" body mass index decreased 2.8% (p<0.001), and frequency of attacks of angina decreased 50.8% (p<0.001; compared with group " C" p<0.001). Statistically significant differences were registered between the following parameters of composite end point and surrogate points: total number of cardiovascular events - 26 (14.8%) vs 47 (27%), p<0.01; number of cardiovascular catastrophes - 5 (3%) vs 15 (8.7%), p<0.05; number of days out of work because of exacerbation of IHD per 1 person/year - 2.4 vs 4.2, p<0.05 in groups " O" and " C" , respectively. Thus in the group " O" positive effect of PT on the course and outcomes of the disease was registered compared with the group " C" .The data obtained are indicative of sufficient efficacy of the used program of PT and feasibility of its application in practice of ambulatory rehabilitation of patients with IHD - survivors of acute coronary events. It also can be looked upon as a method of secondary prevention as results of the study showed its positive impact on risk factors and outcomes of the disease.
To study action of medication in combination with free-choice bicycle exercise on cerebral and peripheral hemodynamics in patients with chronic heart failure (CHF) of functional class II-III.At admission to hospital and at discharge 100 patients with CHF of NYHA functional class (FC) II-III hospitalized for progression of CHF have undergone clinical examination, Doppler echocardiography and biomicroscopy of conjunctival vessels. The patients were randomized into two groups: group 1 of 60 patients received standard drugs and exercised on bicycle: group 2 of 40 patients received standard drugs only.The patients of group 2 achieved better hemodynamic effect, greater lowering of total peripheral vascular resistance. In patients with CHF FC II cardiac output increased due to improvement of left ventricular systolic function (end-systolic and end-diastolic volumes reduced by 20.3 and 38.7%, respectively, ejection fraction increased by 13.7%); in patients with FC III--due to improvement of diastolic function (end-diastolic volume reduced by 8.3%). Bicycle exercise in combined treatment of FC II CHF provides improvement in perivascular and intravascular components of microcirculation by 46.7 and 24.3%, respectively. In FC III CHF intravascular microcirculation improved by 24.3%.Bicycle exercise of patients with CHF of FC II and III used as an adjuvant to standard drugs has an additional positive effect on central hemodynamics and microcirculation.
Severe burn injury (BI) is accompanied by disturbed microcirculation, water-electrolyte and acidbase imbalance within 2-3 days after the accident, and the development of toxemia within 4-12 days. The severity of toxemia depends on the area and depth of the lesion, resorption of tissue decay products, and development of a systemic inflammatory response syndrome. In the patients suffering with deep BI sepsis, it develops in 15% of cases. Pathogenesis of critical conditions is related to the functional activity of myeloid cells, including neutrophilic granulocytes (NG). Тhe determination of NG’s dysfunctions in patients with BI is important, both for prediction of septic complications and administration of rational therapy. The aim of our work was to study the functions of neutrophils in patients with severe BI and to determine early predictors of burn-associated sepsis. The study involved 53 patients with severe BI at the mean age of 43 years (32 to 52); the area of damage was 43% (17 to 63) of the body surface, with deep-burn area of 17 (13 to 27) %. The severity of BI was assessed using the Frank index, at the average value of 74 conventional units (62 to 89). Тwo groups of patients were identified: 24 persons without sepsis, and 29 people with sepsis and severe sepsis. The studies were carried out upon admission, on the 1st, 3rd, 5th, 10th , and 20th day of the burn disease. We determined the numbers of NGs expressing CD18+, CD14+, defensin+; serum contents of soluble defensins (sDеf), IL-6, IL-8 levels (ELISA); procalcitonin, as well as luminol-mediated spontaneous аnd induced NG chemiluminescence. Тhe results of this study showed a relationship between the amounts of NGs containing antimicrobial peptides, contents of NGs expressing CD18+ adhesion molecules, activation of oxidative metabolism, IL-6 overproduction, and development of sepsis in patients with burn injury, as well as with severity of burn trauma.
