[Specific features of the pathology of the respiratory system in SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) infected Syrian hamsters (Mesocricetus auratus)].

INTRODUCTION: Verification of histological changes in respiratory system using Syrian (golden) hamsters (Mesocricetus auratus) as experimental model is an important task for preclinical studies of drugs intended for prevention and treatment of the novel coronavirus infection COVID-19.The aim of this work was to study pathological changes of pulmonary tissue in SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) experimental infection in Syrian hamsters. MATERIAL AND METHODS: Male Syrian hamsters weighting 80-100 g were infected by intranasal administration of culture SARS-CoV-2 at dose 4 × 104 TCID50/ml (TCID is tissue culture infectious dose). Animals were euthanatized on 3, 7 and 14 days after infection, with gravimetric registration. The viral load in lungs was measured using the polymerase chain reaction (PCR). Right lung and trachea tissues were stained with hematoxylin-eosin and according to Mallory. RESULTS AND DISCUSSION: The highest viral replicative activity in lungs was determined 3 days after the infection. After 7 days, on a background of the decrease of the viral load in lungs, a pathologically significant increase of the organ's gravimetric parameters was observed. Within 3 to 14 days post-infection, the lung histologic pattern had been showing the development of inflammation with a succession of infiltrative-proliferative, edematousmacrophagal and fibroblastic changes. It was found that initial changes in respiratory epithelium can proceed without paranecrotic interstitial inflammation, while in the formation of multiple lung parenchyma lesions, damage to the epithelium of bronchioles and acinar ducts can be secondary. The appearance of epithelioid large-cell metaplastic epithelium, forming pseudoacinar structures, was noted as a pathomorphological feature specific to SARS-CoV-2 infection in Syrian hamsters. CONCLUSION: As a result of the study, the specific features of the pathology of the respiratory system in SARSCoV-2 infected Syrian hamsters were described. These findings are of practical importance as reference data that can be used for preclinical studies to assess the effectiveness of vaccines and potential drugs.

Mechanisms of Pulmonary Toxicity of Perfluoro-n-Alkane Pyrolysis Products with Consideration of the Structural Features of the Blood-Air Barriers.

Perfluoroisobutylene a is pulmonotoxic chemical generated during pyrolysis of perfluoro-nalkanes (polytetrafluoroethylene). The mechanisms of acute pulmonary toxicity induced by perfluoroisobutylene have not been studied yet. The analysis of tissues of brown frogs showed that the products of polytetrafluoroethylene pyrolysis induce typical inflammatory response in the lungs (fluid accumulation, erythrocyte stasis, desquamation of the epithelium, and capillary plethora in lung septa) and oropharyngeal cavity (degeneration of ciliated epithelium, hyperemia of underlying vessels with plasmatic imbibition of the connective tissue, and margination of segmented leukocytes and monocytes). The absence of surfactant is a specific feature of the blood-air barrier of the oropharyngeal cavity in frogs compared to the lungs. It can be hypothesized that toxic effects of perfluoroisobutylene are determined by its influence on epithelial (pneumocytes and cells of nonkeratinized stratified ciliated epithelium) and endothelial cells. Even though the effects of the agent on surfactant cannot be excluded, they do not determine the probability of development of inflammatory response.

A model of cerebral circulation disorders created by staged ligation of the common carotid arteries.

A model of brain ischemia induced by staged ligation of the left and right common carotid arteries has been developed in experiments on rats. The use to this model led to reduction of animal mortality. On days 2-5 after the second ligature, the animals lost weight, the level of their CNS vulnerability increased, the volume of perceived information reduced, adaptation to environmental conditions and reproduction of conditioned reflexes were disordered. Focal and diffuse destructive changes in the nerve and glia cells were found in the cerebral cortex, hippocampus, and thalamic nuclei. The severity of disorders in the blood supply to the brain depended on the interval between ligation of the carotid arteries. This recommends this model for evaluation of the efficiency of drugs of various pharmacological groups.

[The role of serotonin and histamine in the neurohumoral mechanisms of postirradiation diarrhea in rats]. / O roli serotonina i gistamina v neirogumoral'nykh mekhanizmakh postluchevoi diarei u krys.

In experiments with rats exposed to 200 Gy radiation it was shown that the diarrhea effect of serotonin under the effect of radiation is implemented via D- and M-type receptors, and that of histamine via H1 and H2 receptors. Serotonin and histamine, that were released under the effect of radiation from endocrine and mast cells of the digestive tract, stimulated the propulsion activity of the intestine whereas histamine, in addition, inhibited the absorption process. It is suggested that serotonin and histamine antagonists should be used as means of preventing of radiation-induced diarrhea.

[Mechanism of circulatory disorders in animals irradiated at high doses]. / K mekhanizmu rasstroistv krovoobrashcheniia u zhivotnykh, obluchennykh v bol'shih dozakh.

Some data are reported on pathoanatomical changes, a status of the microcirculatory channel and the coagulogram of animals affected by high doses of ionizing radiation. The signs of disseminated intravascular blood coagulation have been revealed. The authors discuss the relationship between clinical manifestations with coagulopathy development and circulatory disturbances during intestinal and cerebral forms of acute radiation sickness.

[Antiviral activity of modified RNAses]. / Protivovirusnaia aktivnost' modifitsirovannykh RNK-az.

Antiviral activity of pancreatic RNase and RNase from Act.rimosus modified by various dextran derivatives was studied with respect to aphthosa and Ayzeku disease viruses. Antiviral activity of pancreatic RNase modified by dextran m-aminobenzylhydroxymethyl ether was lower than biological activity of RNase from Act.rimosus modified by the same dextran. Antiviral activity of pancreatic enzyme modified by dialdehyde dextran also changed insignificantly. Modification by dextran hydroxyethylsulfonylanisole ether, dextran m-aminobenzylhydroxymethyl ether in the presence of pyridine or dextran sulfate resulted in a more pronounced increase in antiviral activity of pancreatic enzyme. Therefore, biological activity of the modified nucleases depended on the nature of the enzyme and dextran modifying it.

[Comparative study of the antiviral activity of pancreatic and microbial RNAse]. / Sravnitel'noe izuchenie protivovirusnoi aktivnosti pankreaticheskoi i mikrobnykh RNK-az.

The efficacy of pancreatic RNase with microbial enzymes (RN-ases) of Act. rimosus and Bacillus intermedius) was studied comparatively in vitro in a transplantable cell culture of the swine embryokidney with respect to the aphthosa virus (AV) and the virus of the Aujeszky disease (VAD). The VAD proved to be most sensitive to RNases. RNase of Bac. intermedius showed the highest antiviral efficacy. The enzymes were active in vivo, when the albino mice and newborn rabbits were infected with the AV, the RNase of Bac. intermedius being also most active in this case.

[Effect of body regulatory mechanisms on the catalytic activity of exogenous enzymes]. / Vliianie reguliatornykh mekhanizmov organizma na kataliticheskuiu aktivnost' ékzogennykh fermentov.

An increase in the activity of RNAase in the organs and tissues of mice after administration of exogenous RNAases (pancreatic and actinomycetous) was studied. It was found that the increase in the RNAase activity was higher after administration of the actinomycetous enzyme. This was due to the difference in the sensitivity of the exogenous enzymes to the inhibitor of the mouse RNAase. The pancreatic RNA ase was much more senstive to the inhibitor. The capacity of the mouse blood serum to inhibit trypsin and chymotrypsin of the cattle pancreas, protease of Asp. terricola (terrilytin) and papain was also studied comparatively. It was shown that the pancreatic proteases were more senstive to the serum inhibitor. It is suggested that enzymes less sensitive to the effect of the host regulatory mechanisms (targets), i.e. enzymes of lower organisms, such as microbes and plants should be used in the enzyme therapy for increasing the catalytic activity of the host.