Anna V. Rvacheva

Background. Reseaching of the properties of β-adrenergic receptors (β-AR) is an urgent area in both fundamental and applied medicine. One of the most exact ways to determine the characteristics of β-AR is the radioligand method using [125I]cyanopindolol. This method сan determine the binding activity of β-AR on human blood cells. It is especially important to study the receptor link under the influence of various external factors and drugs. Aims — to evaluate the binding activity of β2-AR on T-lymphocytes of peripheral blood cells using radioligand analysis in healthy volunteers and in professional athletes under the influence of cholinergics. Methods. Healthy volunteers and athletes were given methacholine inhalation. Blood sampling was carried out initially on a clean background and after the methacholine test. To level out the differences in the conditions of formulation and to bring the results to the same coordinate system, the evaluation of the characteristics of β-AR in the framework of the study was carried out according to the specific binding index (ISS) — value reflecting the proportion of specific binding of receptors from the total specific. Results. During the study, when dividing volunteers into smokers and non-smokers, a tendency to decrease binding activity was noted. As a result of the study, in the general group of volunteers was registerd a significant decrease in the binding activity of beta2 receptors under the influence of methacholine. In the group of athletes, no significant changes were kept. Conclusions. The reason for these results may be both intense training, which changes the number of receptors, and the presence or absence of eosinophilic inflammation. The smoking factor does not play a significant role.

Background: Comorbid cardiovascular and bronchoobstructive diseases worsens disease course and prognosis and causes difficulties in therapy. Effectiveness 2-agonists (cornerstone of bronchoobstructive pathology treatment) depends on -adrenoreceptors state. Therefore, a detailed study of the functional state of beta-adrenoreceptors is necessary. Aim: to evaluate the relationship of changes in the characteristics of 1- and 2-adrenoreceptors, against the background of the use of 2-agonists in patients with cardiovascular and bronchoobstructive diseases with clinically significant parameters. Methods: In the pilot single-center prospective study during 2.5 years 45 patients (15 with cardiovascular and 30 with bronchoobstructive diseases) were included. Anamnestic data and complaints were collected and laboratory and instrumental studies were performed. Modified radioligand analysis on blood T-lymphocytes using radiolabeled Cyanopindolol and unlabeled selective ligands (ICI 118551, CGP 20712) before and after salbutamol and formoterol was performed and the binding activity of 1- and 2-adrenoreceptors was determined. Results: The correlation analysis between clinically significant parameters and changes in the specific binding index of 1- and 2-adrenoreceptors confirmed its clinical relevance. In test with beta-agonists in cardiovascular and bronchoobstructive diseases patients, an increase in the specific binding index of 1-adrenoreceptors is associated with clinical, laboratory and instrumental parameters of a favorable course of the disease, and an increase in the specific binding index of 2-adrenoreceptors is associated with negative. In the cardiovascular group without bronchoobstructive diseases with salbutamol an increase in the specific binding index of 1-adrenoreceptors was associated with parameters of unfavorable disease course, while an increase in the specific binding index of 2-adrenoreceptors did not have a clear associative relationship with clinical characteristics. Conclusions: The association of changes in the specific binding index of 1- and 2-adrenoreceptors in patients with cardiovascular and bronchoobstructive diseases with clinically significant parameters during acute tests with short- and long-acting 2-agonists was revealed, which in the future may provide an opportunity to identify patients with an unfavorable course of the disease.

Over the two years of the novel coronavirus infection (COVID-19) pandemic, there has been an evolution of views in various fields of medicine, which has led to a powerful development of scientific research in the field of epidemiology, clinic, diagnosis and therapy of COVID-19. This article discusses the evolution of views and approaches to the study of the clinic and therapy of COVID-19. The symptoms and aggravation of the course of cardiovascular diseases with COVID-19 have been established. The main strategy for organizing surgical care for patients with COVID-19 is indicated. The main criteria for the treatment of COVID-19, the need to prescribe SGCS on an individual basis, and the need to search for new methods of anti-inflammatory therapy for COVID-19, one of which may be the use of alkylating drugs in ultra-low doses, are described.

Over the two years of the novel coronavirus infection (COVID-19) pandemic, there has been an evolution of views in various fields of medicine, which has led to a powerful development of scientific research in the field of epidemiology, clinic, diagnosis and therapy of COVID-19. The article highlights the evolution of views and approaches to the study of the epidemiology and radiology of COVID-19. The data of molecular genetic studies are shown, which are the most important component of epidemiological surveillance. The study of the manifestations of the COVID-19 epidemic process made it possible to distinguish two stages in the development of the epidemiological situation in the Russian Federation. At the first stage of the epidemic, two rises in the incidence rate of the population were recorded, regulated by social and natural factors. The second stage of the epidemic was due to a change in the biological properties of the SARS-CoV-2 virus, followed by a change in the prevailing genovariants (Alpha, Delta and Omicron). At the second stage of the epidemic, three rises in the incidence of the population were recorded. The general principles for the use of radiodiagnosis methods, which are used primarily to detect lung damage in COVID-19, are given. With the accumulation of experience, a natural change in ideas about the algorithms for the use of visualization technologies has occurred.

Background. One of the most important components of COVID-19 therapy is the suppression of the hyperergic immune response. There is an urgent need of creating the optimal tactics of efficient and safe anti-inflammatory therapy. A new method of treatment of COVID-19 with inhalation of ultra-low (non-cytotoxic) doses of the alkylating drug melphalan is proposed, based on previous experimental, preclinical, and clinical data on its use in severe bronchial asthma.The aim. To evaluate the efficacy and safety of inhalation of ultra-low doses of melphalan in hospitalized patients with COVID-19-associated lung damage.Materials and methods. A prospective, open, controlled, blind for the central expert study was conducted. Sixty adult patients were included, 30 patients were consecutively admitted to the hospital and received nebulized inhalations of 0.1 mg of melphalan for 7 days. Thirty patients of the control group were selected by an independent expert retrospectively using the computer algorithm for selecting «close» patients based on the «case-control» principle. The primary endpoints were the dynamics on the WHO Clinical Improvement Scale and the dynamics of dyspnea according to the modified Borg scale, secondary – assessment of adverse events, dynamics of indicators of clinical, biochemical blood tests, lungs computed tomography data from the beginning of inhalations in the melphalan group and from the corresponding day in the control group.Results. Inhalations of melphalan led to a significant improvement in the clinical condition of patients according to the WHO scale, decrease in the intensity of dyspnea on day 7 of treatment and by the time of discharge, a significant anti-inflammatory effect. Adverse events and dynamics of laboratory parameters did not differ from the control group.Conclusion. The method of treatment of COVID-19 by inhalation of ultra-low doses of the alkylating drug melphalan is safe and leads to a significant clinical improvement of hospitalized patients with COVID-19-associated lung damage.

The aim of the work was to justify the algorithm of outpatient drug therapy in patients with COVID-19, based on the principle of «Multi-hit» Approach. The algorithm is based on the published results of clinical studies and observations, authors’ own practical experience in the use and management of more than 4 thousand patients diagnosed with COVID-19 of varying severity during the 2020 pandemic. The article substantiates a complex algorithm for the treatment of outpatients with COVID-19, which includes etiotropic, pathogenetic, and symptomatic components of therapy with different mechanisms of action. The described approach is the 1st stage (outpatient) of a complex algorithm for managing patients with COVID-19. It has been successfully implemented in the system of outpatient care for patients with novel coronavirus infections in several leading medical institutions in Russia. The authors believe that the developed algorithm for providing outpatient drug therapy for COVID-19, based on the principle of multiple exposure, may be useful in real clinical practice of managing patients with coronavirus infection.

Currently, the increase in comorbid pathology, including patients with bronchoobstructive and cardiovascular diseases remains an urgent problem. Therefore, there is a need not only for new approaches in the tactics of management and treatment of patients with combined cardiorespiratory pathology, but also a more complete understanding of the impact of existing bronchodilator therapy on comorbid pathology and the pathophysiological changes taking place in order to create a new approach to the diagnosis and selection of effective and optimal treatment. The article provides a review of the literature on the impact of beta-2-agonists on pro- and anti-inflammatory mechanisms in patients with bronchial obstruction, including cardiovascular disease.

To study the specific features of an immune response and the role of infectious pathogens in the occurrence, development, and maintenance of ventricular ectopic activity in patients without signs of organic disease of the cardiovascular system (CVS). The investigation enrolled 91 patients (27 men and 64 women with a mean age of 36.5 +/- 11.5 years) with premature ventricular contractions (PVC) without signs of organic CVS pathology. A control group comprised 31 healthy volunteers. In addition to standard physical examination, a study of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cellular and humoral immune parameters was performed and the serological and molecular genetic markers of infections were determined in all the patients. The persons with PVC, as compared to the control group, were recorded to have a higher NT-proBNP level (49.2 pg/ml versus 25.4 pg/ml; p = 0.001) accompanied by an increase in both the total number of PVC and the number of coupled PVC and the episodes of ventricular tachycardia. They were also found to have elevated CD3(+)HLA-DR+ (2.4% versus 1.56%) and CD3(+)CD95+ (27.6% versus 18.8%) counts (p = 0.001). In patients with a C-reactive protein level of more than 2 mg/l, the total number of PVC was larger than that in the other patients (p = 0.065). The patients with PVC did not show a statistically significant difference from the controls in the levels of antiviral and antibacterial antibodies. The people with PVC displayed a number of relationships between the infectious pathogen antibody titers and the ECG Holter monitoring and echocardiography readings. In the patients with PVC without signs of organic CVS pathology, the parameters of an immune response were not different from those obtained in the control group, which was likely to be associated with the involvement of the immune system in the development and maintenance of ventricular arrhythmias.

To study the effect of bosentan on the clinical status and cellular immunity of patients with idiopathic pulmonary hypertension (IPH). The study enrolled 35 patients with Functional Class (FC) II and IV IPH who had received conventional therapy for 3 months. All the patients took bosentan 125 mg/day for 4 weeks. Then they were randomized to have bosentan 125 or 250 mg/day (Groups 1 and 2). FC was assessed and 6-minute walk test (6MWT), transthoracic echocardiography (EchoCG), and right heart catheterization (RHC) were performed at baseline and after 12 weeks. Peripheral blood lymphocytes were immunophenotyped and the functional activity of neutrophils was determined by their ability to absorb latex particles at baseline and following 3 and 12 weeks. After 12 weeks of treatment, both groups showed a statistically significant increase in the distance covered during the 6MWT. The Borg index and FC also decreased statistically significantly. EchoCG demonstrated a statistically significant reduction in systolic pulmonary artery pressure (SPAP) in Group 1; and in Group 2, SPAP was lower at baseline and remained substantially unchanged (it statistically significantly decreased as evidenced by RHC). Bosentan statistically significantly diminished pulmonary vascular resistance in both groups. No adverse reactions were noted. At baseline, the patients showed a statistically significant elevation in NKT-like lymphocytes up to 10.79 +/- 6.2%. The other indicators of peripheral blood lymphocyte phenotyping did not exceed the normal range. The count of NKT-like lymphocytes remained significantly above the normal levels throughout the follow-up in both groups and slightly dropped in Group 1 patients only after 12 weeks of treatment. In Group 2, the level of CD3+CD25+ lymphocytes rose as compared to the normal levels at 3 and 12 weeks of treatment. At 3 weeks of treatment, there was a statistically significant difference between the groups in phagocytic number. Bosentan treatment statistically significantly improves the clinical status of patients with IPH and it is characterized by good tolerability. Bosentan does not exceed the normal count of peripheral blood NKT-like lymphocytes, but it has a direct or indirect positive effect on the B-lymphocytic component of the immune system in patients with IPH.