Cholecalciferol as a means of nonspecific immunoprophylaxis against COVID-19

The current direction of scientific research in recent years has been the study of the immunobiological properties of vitamin D. The purpose of this work was to analyze the results of oral administration of cholecalciferol in order to prevent infection with the SARS-CoV-2 virus in the first wave of the COVID-19 pandemic. The study was performed in the period from October 07 to December 29, 2020, when there were no immunobiological drugs for specific prevention of COVID-19. The total number of respondents was 73 people; all had been ill with coronavirus only once. The etiological diagnosis of the disease included molecular genetic testing of samples of two localizations obtained by the conventional method (nasopharynx, oropharynx). The concentration of antibodies to the virus was determined on average 2 months after the disease using a set of reagents SARS-CoV-2-IgG quantitative-ELISA-Best (JSC Vector-Best, Russia). An approximate assessment of IgM concentration was carried out using a set of SARS-CoV-2-IgM-ELISA-Best from the same manufacturer. Among the study participants were those who used immunobiological drugs for the prevention of infection (riamilovir, umifenovir hydrochloride monohydrate, human recombinant interferon alpha-2b, zinc acetate, vitamin C). In particular, 28 people (38.4%) took cholecalciferol (group No. 1) and 45 people (61.6%) did not use this (group No. 2). Statistical processing of the obtained data was performed using the statistical package STATISTICA v.12.5.192.5 (StatSoft, Inc., USA). We applied the analysis of basic statistics, Linear Discriminant Analysis, Kolmogorov–Smirnov test, Chi-Square test, Wald–Wolfowitz Runs Test, Kruskal– Wallis test. Differences in the incidence of respiratory distress syndrome of the two studied groups were revealed: in patients taking cholecalciferol, the syndrome did not develop at all; in group No. 2, it was registered in 20.0% of cases (Chi-Square = 5.242, p = 0.02). In addition, in patients of group No. 1, the concentration of IgG 2 months after the disease was 3.8 times higher than the values in group No. 2 (Chi-Square = 9.268, p = 0.003). Similar differences were found for the IgM level (Wilks' Lambda: 0.659 approx. F (7.32) = 2.367 p < 0.045). It was known that in both groups there were respondents who used other immuno-active substances for preventive purposes. In the first group there were 18 people (24.7% of all); in the second, there were 13 people (17.8% of all). It was found that those who used other immuno-active substances and did not take vitamin D suffered the disease more easily than everyone else. The respondents who did not use any immunoprophylactic agents were the next in terms of the severity of the infection. The respondents who took cholecalciferol mainly assessed the severity of the infection as average. The study participants who took both vitamin D and used other means of prevention suffered the most from COVID-19. Respondents who took cholecalciferol more often than others reported long-term fatigue, exacerbation of chronic and the appearance of new diseases (hypertension, cardialgia, bronchial asthma, allergies, decreased visual acuity), muscle, joint and vertebral pains that appeared for the first time. The phenomenon of arthralgia and other lesions of large joints in COVID-19 was described by us earlier. Studies by other authors also report frequent complaints of increased fatigue and joint pain. At the same time, the role of vitamin D is considered exclusively from the standpoint of vitamin deficiency in a new coronavirus infection and its potential role in inhibiting hyperinflammatory reactions, as well as accelerating the healing process of affected areas, especially in lung tissue. It was found that vitamin D intake did not affect the incidence of fever, the incidence of pneumonia, the volume of lung tissue damage (based on computed tomography data), the duration of hospitalization and the disease as a whole, and also did not prevent the development of anosmia and dysgeusia. The use of vitamin D as a protective agent to prevent infection with the SARS-CoV-2 virus has had an impact on reducing the frequency/ prevention of cases of respiratory distress syndrome during the disease. Also, those who took vitamin D recorded an increase in the formation of IgG to the SARS-CoV-2 virus 2 months after infection 3.8 times higher than the values recorded in respondents who did not take cholecalciferol. The participants who took cholecalciferol suffered the infection more severely, especially if they used any other protective substances. Also, with the preventive intake of vitamin D after COVID-19, increased fatigue persisted longer, the appearance of new and activation of chronic diseases and muscle, joint and vertebral pains that appeared for the first time were reported more often, which correlates with the data we received earlier

Thermal radiation of conducting nanoparticles

The thermal radiation of small conducting particles was investigated in the region where the Stephan-Boltzmann law is not valid and strongly overestimates radiation losses. The new criterion for the particle size, at which black body radiation law fails, was formulated. The approach is based on the magnetic particle polarization, which is valid until very small sizes (cluster size) where due to drop of particle conductivity the electric polarization prevails over the magnetic one. It was also shown that the radiation power of clusters, estimated on the basis of the experimental data, is lower than that given by the Stephan-Boltzmann law.Comment: 12 pages, 5 figures, 1 tabl

Non-reciprocal light scattering by lattice of magnetic vortices

We report on experimental study of optical properties of two-dimensional square lattice of triangle Co and CoFe nanoparticles with a vortex magnetization distribution. We demonstrate that intensity of light scattered in diffraction maxima depends on the vorticity of the particles magnetization and it can be manipulated by applying an external magnetic field. The experimental results can be understood in terms of phenomenological theory.Comment: 10 pages, 4 figure

«Сепсис-3»: новая редакция - старые проблемы. Анализ с позиции общей патологии

Sepsis-3 Guidelines defines sepsis as an organ dysfunction caused by dysregulated host response to infection. To record organ dysfunction, the SOFA/quick SOFA scales were recommended. In fact, in medical practice, sepsis is considered nothing more than a critical infection that requires intensive care. Therefore, sepsis is pathogenetically a non-homogeneous condition manifested by diverse nosologies and syndromes. Unlike the previous two editions, Sepsis-1 and Sepsis-2 Guidelines, the formal criteria provided in the Sepsis-3 are closer to the de facto position, describe more specific, but less sensitive features to predict mortality. However, the initial, latent manifestations of critical conditions, which can be relatively effectively controlled by intensive therapy, remain outside the Sepsis-3 criteria. Not all signs of multiple organ dysfunctions (according to the Sepsis-3 criteria) will require intensive care. Hence, obviously the presence or absence of formal criteria of Sepsis-3 will not be always taken into account while verifying sepsis. The only relatively pathogenetically homogeneous definition in Sepsis-3 is “septic shock”. However, it also does not fully consider the staging (according to the degree of compensation of hemodynamic disturbances) and the phasing (according to the severity of the pro-inflammatory response) of the dynamics of the shock condition. From our point of view, a positive result of the Sepsis-3 consensus would be in transition of the systemic inflammatory response syndrome (SIRS) from the main to additional (optional) verifying sepsis criteria. We also believe that the weak side of the Sepsis-3 Guidelines is in underestimated mechanisms of systemic inflammation as a general pathological process in the genesis of developing critical conditions of various origins. From the perspective of general pathology, sepsis is a combination of the three common fundamental pathological processes: classical (canonical) and systemic inflammation (SI), as well as chronic systemic low-grade inflammation (parainflammation), the latter can be considered as an unfavorable background for development of the former two processes. All three processes are characterized by any SIR signs and require to be differentiated on the basis of integral criteria, which reflect specific blocks of the SI complex process. The pathogenesis of the SARS-CoV-2 infection (COVID-19) is a relevant example underlying inevitability of such approach. The systemic microvascular vasculitis, and its main clinical manifestations such as systemic microcirculatory disorders in the form of shockogenic conditions is the SI pathogenetic basis. Apparently, one of the modalities for further evolution of critical care medicine will be coupled to development of a more multilayered but effective methods for assessing pathogenesis of critical states and more differentiated methods of pathogenetic therapy. Therefore, it will require to modernize a number of fundamental premises in our knowledge about pathobiology, pathophysiology, and general pathology. © 2021 Saint Petersburg Pasteur Institute. All rights reserved.This work was carried out within the framework of the state assignment of the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences (registration number NIOKTR No. АААА-А18-118020590108-7)

Physiological and pathogenic role of scavenger receptors in humans

The scavenger receptors (SRs)) include > 30 different molecules structurally classified into 11 classes (A to L). They are expressed mostly on stromal macrophages, and their expression may be augmented in direct dependence with concentrations of their ligands. The SRs are heterogenous by their structure, however, being common in their functional potential. E.g., different SR classes may participate in absorption of modified low-density lipoproteins and glycated proteins, apoptotic and ageing cells, altered erythrocytes and platelets, like as a big variety of other endogenous ligands from metabolic and cellular “trash”. A common property of SRs is their participation in removal of small pathogen amounts from blood circulation, regulation of cell and tissue stress responses, ability to form complicated receptor complexes with other receptor types including integrins and toll-like receptors. Opposite to classic pattern-recognizing receptors, the SR involvement does not always elicit a pronounced cellular activation and development of pro-inflammatory cellular stress. The SR functional effects provide interactions between different physiological events and immune system, including the processes of neuroendocrine and metabolic regulation. These mechanisms provide both homeostatic stability and, likewise, act at the border of normal and pathological conditions, i.e., participating in pathogenesis of transitional processes, e.g., physiological ageing. Moreover, the SR-associated processes represent a key pathogenetic factor in different somatic diseases, e.g., those associated with low-intensity chronic inflammation, including obesity, type 2 diabetes, atherosclerosis, arterial hypertension, various neurodegenerative disorders. Similarly, the SRs are involved into the processes of cancer transformation and antitumor response, different processes of classical inflammation, from antigen presentation to the morphofunctional T cell and macrophage polarization in the inflammation foci and immunocompetent organs. SR are playing a controversial role in development of acute systemic inflammation, the main reason for lethal outcomes in the intensive care wards. Targeted effects upon the SRs represent a promising approach when treating a broad variety of diseases, whereas detection of membrane-bound and soluble SR forms could be performed by means of diagnostic and monitoring techniques in many human disorders. © 2020, SPb RAACI

Sepsis-3: new edition — old problems. analysis from the perspective of general pathology

Sepsis-3 Guidelines defines sepsis as an organ dysfunction caused by dysregulated host response to infection. To record organ dysfunction, the SOFA/quick SOFA scales were recommended. In fact, in medical practice, sepsis is considered nothing more than a critical infection that requires intensive care. Therefore, sepsis is pathogenetically a nonhomogeneous condition manifested by diverse nosologies and syndromes. Unlike the previous two editions, Sepsis-1 and Sepsis-2 Guidelines, the formal criteria provided in the Sepsis-3 are closer to the de facto position, describe more specific, but less sensitive features to predict mortality. However, the initial, latent manifestations of critical conditions, which can be relatively effectively controlled by intensive therapy, remain outside the Sepsis-3 criteria. Not all signs of multiple organ dysfunctions (according to the Sepsis-3 criteria) will require intensive care. Hence, obviously the presence or absence of formal criteria of Sepsis-3 will not be always taken into account while verifying sepsis. The only relatively pathogenetically homogeneous definition in Sepsis-3 is “septic shock”. However, it also does not fully consider the staging (according to the degree of compensation of hemodynamic disturbances) and the phasing (according to the severity of the proinflammatory response) of the dynamics of the shock condition. From our point of view, a positive result of the Sepsis-3 consensus would be in transition of the systemic inflammatory response syndrome (SIRS) from the main to additional (optional) verifying sepsis criteria. We also believe that the weak side of the Sepsis-3 Guidelines is in underestimated mechanisms of systemic inflammation as a general pathological process in the genesis of developing critical conditions of various origins. From the perspective of general pathology, sepsis is a combination of the three common fundamental pathological processes: classical (canonical) and systemic inflammation (SI), as well as chronic systemic low-grade inflammation (parainflammation), the latter can be considered as an unfavorable background for development of the former two processes. All three processes are characterized by any SIR signs and require to be differentiated on the basis of integral criteria, which reflect specific blocks of the SI complex process. The pathogenesis of the SARS-CoV-2 infection (COVID-19) is a relevant example underlying inevitability of such approach. The systemic microvascular vasculitis, and its main clinical manifestations such as systemic microcirculatory disorders in the form of shockogenic conditions is the SI pathogenetic basis. Apparently, one of the modalities for further evolution of critical care medicine will be coupled to development of a more multilayered but effective methods for assessing pathogenesis of critical states and more differentiated methods of pathogenetic therapy. Therefore, it will require to modernize a number of fundamental premises in our knowledge about pathobiology, pathophysiology, and general pathology