[Effects of the antioxidant ionol on humoral immune response in experimental influenza]. / Vliianie antioksidanta ionola na gumoral'noe zveno immunogo otveta pri éksperimental'nom grippe.

The effect of the antioxidant ionol on a humoral immune response was studied in experimental influenza. With preventive introduction of ionol, the affinity of anti-influenza G antibodies circulating in the blood stream was shown to be decreased as compared to that in control animals. The changes in the affinity during influenza infection were cyclic and less marked in the group of animals receiving ionol. The administration of the antioxidant substantially reduced the detection rate of specific blood immune complexes and contributed to the production of antibody-forming cells. The findings suggest that ionol has a favourable effect on a humoral immune response in experimental influenza and alleviates the course of an infectious process.

[Role of lipid peroxidation in the pathogenesis of influenza and search for antiviral protective agents]. / Rol' lipoperoksidatsii v patogeneze gripoznoi infektsii i poisk sredstv protivovirusnoi zashchity.

This study has provided evidence for a considerable role of lipid peroxidation in the pathogenesis of murine influenza infection. The virus-induced activation of lipid peroxidation was followed by the enhanced activity of endogenous enzymes of the antioxidative protection system. The preventive effect of an antioxidant and the therapeutical effect of an antihypoxant were recorded in the prevention of murine death due to influenza. The mechanisms of the protective effect of the antihypoxant is due both to its immediate antihypoxant function and its correcting influence on lipid peroxidation.

[Glucose utilization in influenza of varying severity in intact or stressed animals]. / Uvoenie gliukozy na fone grippoznoi infektsii raznoi tiazhesti u intaktnykh ili stressirovannykh zhivotnykh.

Animals preexposed to stress developed manifest hyperglycemia in the first 2 days of influenza infection, which was replaced by prolonged hypoglycemia. The status of carbohydrate metabolism normalized no sooner than 3 to 4 weeks after the disease onset, although the acute phase of infection was over by the end of week 2. The changes were evident in the pattern of "sugar curve" after glucose loading. Glucose utilization failed to normalize even 2 h after the loading in animals with stress, influenza infection, or stress-associated complications of this infection.

[Study of biological equilibrium in the body in viral infection of different degree of severity (on the model of influenza)]. / Biologicheskoe ravnovesie v organizme pri virusnoi infektsii raznoi tiazhesti (na modeli grippa).

The authors made a comparative analysis of the contribution to the outcome of the disease by realization of information of viral genome and host responses in the time-course of simulated lethal and nonlethal mice influenza. They studied the effect of ionol, pathogenetic antioxidant, prevention and depicted absolutely new features of the diseases severity and outlined possible points of effective drug application. The suggested scheme of the time-course measurement of viral involvement of the host body and the formation of its responses could be recommended in the study of mechanisms of the viral infection development and the activity of antiviral agents.

[Post-stress disorders of resistance of mice to recurrent infection by homologous influenza virus]. / Poststressornoe narushenie ustoichivosti myshei k povtornomu zarazheniiu gomologichnym virusom grippa.

A decrease in the mouse resistance to reinfection by influenza virus under the effect of immobilization stress was depicted. Violation in the formation of a long-term resistance to a repeated disease ran in the presence of the high levels of circulating anti-influenza antibodies and not ++always correlated with a post-stress impairment of the formation of antigen-reactive clones of cells in the spleen of primarily infected mice. Prophylactic administration of ionol which prevented a post-stress aggravation of the primary influenza infection failed to produce a favourable effect on the immunity in case of reinfection.

[Pathogenetic mechanisms of stress-induced aggravation of experimental influenza and its prevention]. / Patogeneticheskie mekhanizmy stressovogo usugubleniia éksperimental'noi grippoznoi infektsii i ego preduprezhdenie.

It was stated that in stress-induced aggravation of infection realized in transformation of nonlethal patterns of infection into a lethal one there occurred a manifest dysfunction of hypothalamo-hypophyseal-neurosecretory performance (HHNS) featured by a 2-fold decrease in the blood vasopressin and an essential elevation of the hypothalamic one. The phenomenon is being suggestive of a possible blockage in the hormonal discharge into circulation and the limitation of its participation in the development of defensive and compensatory reactions. Identical HHNS dysfunction was noted in the lethal pattern of the infection. The authors formulated the concept of the main pathogenetic points underlying the damage of vegetative regulation centres. Mechanisms of viral and tissue metabolic damage of CNS were revealed. The authors substantiated the advisability and prospective use+ of antioxidants as applied to the prevention of severe course of influenza and its complications in extremely aggravated patterns.

[The role of lipid peroxidation in post-stress aggravation of influenza and the corrective effect od ionol]. / Rol' perekisnogo okisleniia lipidov v realizatsii poststressornogo utiazheniia grippoznoi infektsii i korrigiruiushchii éffekt ionola.

Activation of lipid peroxidation in the tissues of the lungs, brain and liver which was followed by a compensatory increment in the activity of antioxidative enzymes was demonstrated in experimental mice with isolated or combined effect of immobilizing stress or influenza infection. The usage of antioxidative drug, ionol, decreased the levels of lipid peroxidation, alleviated the aggravated course of the infection which occurred after the preliminary immobilization. The authors substantiated the role of activation of lipid peroxidation as a significant link in the disease progression in case of isolated or combined effect of stress or infection and considered the prospective ways of chemotherapeutic management of viral infections.

[Factors of antiviral resistance in the pathogenesis of influenza in mice]. / Faktory protivovirusnoi ustoichivosti v patogeneze grippoznoi infektsii myshei.

Findings of original research on the factors of nonspecific resistance (interferon formation, antibacterial activity of peritoneal exudate cells, and natural cytotoxicity of splenocytes) and immunity (changes in sub-populational composition of spleen lymphocytes) in different types of influenza in mice are analysed. There was no infection-mediated suppression of the studied reactions, that could have been considered as a cause of death or a basis for immunodeficiency status. The correlation of the level of cerebral lipid peroxidation in mice with severe infection formed the basis for testing the synthetic antioxidant ionol as an anti-influenza agent. A prophylactic effect of ionol toward the development of influenza infection has been obtained. Its possible actions and the feasibility of search for prophylactic and therapeutic preparations among the agents with pathogenetic action is discussed.

[Status of the hypothalamo-hypophyseal neurosecretory system in mice with anaphylactic shock caused by administration of homogenates of lung tissue from influenza virus-infected and non-infected animals]. / Sostoianie gipotalamo-gipofizarnoi sistemy pri anafilaktoidnom shoke u myshei,vyzvanom vvedeniem gomogenatov legochnoi tkani ot ne zarazhennykh i zarazhennykh virusom grippa zhivotnykh.

A significant increase in the lethal action of the homogenates obtained from animals infected with APR/8/34 influenza virus, as compared to the non-infected mice, was established using an experimental anaphylactoid shock model in CBA and (CBA x C57Bl)F1 mice by administering the lung tissue homogenates obtained from syngeneic donors. This increase was directly related to the inoculation dose (3.5 and 5.5 lg ED50) and infection development terms (days 2-3 or 5 after inoculation) but was not directly virus-mediated. It was found that in generally non-specific action of the lung tissue homogenates from non-infected and influenza-infected mice on the cellular structures of the viscera (liver, lungs) causing their damage and animal death, the infected lung homogenates show certain selectivity toward the hypothalamo-hypophyseal-neurosecretory system (HHNS) by blocking its reaction in anaphylactoid shock development, impairing the transport of neurohormones and their release into the neurohemal complex. The fact that the tissue products from the focus of influenza infection may affect the central mechanisms responsible for hemostatic control is thus demonstrated.

[Dynamics of peroxidation of brain tissue lipids in mice infected with influenza virus in the presence of immobilization stress]. / Dinamika perekisnogo okisleniia lipidov mozgovoi tkani myshei, zarazhennykh virusom grippa na fone immobilizatsionnogo stressa.

The poststress activation of peroxide oxidation reaction (POL) of lipids from brain tissue of the mice CBA and FI (CBA X C57 Black) has been confirmed. The principal difference in the nature of malonic dialdehyde level dynamics in brain tissue determined by a form of infectious process induced by influenza strain A/PR/8/34 pathogenic for mice has been found. The sublethal dose has been shown to activate while the lethal dose to suppress the POL process. Progression of influenza infection at the stress background was accompanied by a sharp unidirectional increase in MDA content in mice brain tissue. The increase was mostly expressed in case of mice infection with a lethal dose of the virus. The data obtained suggest a membrane mechanism for barrier damage as a reason of severing influenza infection by the stress background.

Experimental influenza infection: influence of stress.

The effect of immobilization stress on the course of various forms of influenza infection has been investigated. Influenza was produced in 10-14-week-old inbred mice by intranasal infection with pathogenic influenza virus strain A/PR/8/34 (H1N1) at different doses. Immobilization for 6 hr resulted in the appearance of virus-inhibiting activity in the serum of mice. This activity suppressed the reproduction of test-virus in tissue culture, it was resistant to acid pH 2.0 treatment and to heating at 56 degrees C. However, the high level of virus-inhibiting activity failed to protect the animals from subsequent development of lethal influenza infection. Immobilization stress caused a transient depression of virus induced interferon (IFN) production, as revealed by the use of virus inducer at early intervals after stress. Contemporarily, the stress could aggravate the course of virus infection promoting its transition from non-lethal form into a lethal one and virus penetration into brain.

[Molecular and cellular bases for the effects of interferon]. / Molekuliarnye i kletochnye osnovy éffektov interferonov.

The data on the molecular mechanisms of interferons activity are analyzed. The analysis is based on the assumption that interferons are the substances of the hormonal nature. The initial step of the different interferons effects is attempted to be explained by the existence of the molecular and cellular reactions common for its realization. The dependence of the final results of interferons action on the metabolic processes in different cells and tissues determined by the specific functions and physiology of the latter is assumed.

[Dynamics of change in the antibacterial activity of mouse peritoneal cells during the development of experimental influenzal infection]. / Dinamika izmeneniia antibakterial'noi aktivnocti peritoneal'nykh kletok myshei pri razvitii éksperimental'noi grippoznoi infektsii.

The method of the radiometric determination of the antibacterial activity of peritoneal cells in the process of the development of viral infection has been approved. The genetically determined specific level of the antibacterial activity of these cells in different strains of mice has been established. The development of the lethal form of experimental influenza A in mice has been shown to be accompanied by the mobilization of nonspecific protective factors, including the system of interferons and the antibacterial activity of peritoneal cells. The latter factor is, seemingly, insufficient for ensuring the necessary level of protection in the animals, whose death occurs at a shorter time than that necessary for the development of specific immune response.

[Effect of immobilization stress on the course of experimental influenza infection and the process of interferon formation]. / Vliianie immobilizatsionnogo stressa na techenie éksperimental'noi grippoznoi infektsii i protsess interferonoobrazovaniia.

The experimental data on the peculiar features of interferon production in C57BL/6 mice, infected with the lethal dose of influenza virus and simultaneously subjected to the action of a stress factor, are presented. Immobilization stress was found to exert pronounced influence on the interferon-producing system of the body, which was manifested by the appearance of alpha interferon in a titer of up to 1:80 in the blood of intact animals. 6-hour immobilization preceding infection did not accelerate the development of the lethal from of influenza infection, but sharply suppressed the viral induction of the synthesis of interferon.