[Mechanisms of realization of protective effect of miliacin during experimental Salmonella infection: effect of endotoxinemia and cytokine production].

AIM: Evaluate the effect of miliacin on the intensity of endotoxinemia and features of cytokine production in experimental salmonella infection. MATERIALS AND METHODS: The studies were carried out in 128 male mice (CBAxC57Bl6)F1 divided into 4 groups: I--intact; II--infected; III--infected after administration of miliacin solvent: tween-21; IV--infected after administration of miliacin. Determination of the endotoxin in blood plasma was carried out by using chromogenic LAL-test. Cytokine production was studied in splenocyte culture by EIA method. RESULTS: Miliacin reduced the intensity of endotoxinemia in mice of group IV. Salmonella infection increased spontaneous (IFNγ) and induced (IL-12, IFNγ, IL-17) cytokine production. Miliacin ensured the most significant increase of spontaneous IL-10, IL-12 and IFNγ production compared with groups II and III. At the same time it limited the increase of induced IL-17 production compared with groups II and III. CONCLUSION: Protective effect of miliacin is determined by the reduction of endotoxinemia, mobilization of Th-1 response, stimulation of IL-10 production and limitation of IL-17 participation in the development of the inflammatory reaction.

[The natural triterpenoid miliacin prevents methotrexate-induced oxidative stress and normalizes the expression of genes encoding the cytochrome P-450 2E1 isoform and glutathione reductase in the liver].

We studied the role of the natural triterpenoid miliacin (3-3-methoxy-Al8-oleanene) in the regulation of oxidative stress in the liver of (CBAxC57B1(6))F1 mice exposed to methotrexate. Miliacin attenuated methotrexate-induced lipid peroxidation as determined by an attenuation of thiobarbituric acid-reacting products in the liver. Furthermore, miliacin normalized the expression of genes encoding the 2e1 isoform of cytochrome P-450 and glutathione reductase that were dramatically dysregulated by methotrexate. These results established the role of miliacin in modulation of redox genes, thereby providing evidence for a new mechanism of organ protection by this triterpenoid.

[Protective effect of miliacin during experimental salmonellosis infection].

AIM: Evaluation of influence of triterpenoid miliacin on the development of experimental salmonellosis infection. MATERIALS AND METHODS: Studies were carried out in 330 male mice (CBAxC57Bl6)F1. Miliacin was administered 3 times intraperitoneally with the interval of 3 days between administrations at a single dose of 2 mg/kg. The animals were infected intraperitoneally by hospital origin Salmonella enteritidis strain (2x10(6) bacteria per mice). 4 groups of mice were used: I - intact; II - infected; III - infected after administering solvent for miliacin 3 times (tween 21 at final concentration of 1.6x 10(-7) mol/kg); IV - infected after administration ofmiliacin. RESULTS: Miliacin reduced the mortality of mice compared with groups II and III. Microbial contamination of mice spleen in group IV was significantly lower compared with group II at all the periods of the study, and liver - at days 10 and 15. Triterpenoid weakened cell depletion of bone marrow, thymus and limited hyperplasia of spleen compared with animals of groups II and III. Its protective effect did not correlate with increase of antibody titers. CONCLUSION: Miliacin weakens the severity of salmonellosis infection course.

[The development of secondary immunodeficiency in body when exposed to the effect of xenobiotics with immunosuppressive activity].

The State Education Institution of Higher professional education "The Orenburg State Medical Academy of Federal Agency in Public Health and Social Development". In the experiment on mice (CBA x C57Bl6) F1 and Wistar rats is shown the protective effect of triterpenoid plant--miliatsina (3-beta-methoxy-delta18-oleanena) in relation to the humoral immune response and clearance macrophage function hepatic xenobiotic conditions of use--methotrexate. The results define the term as used miliatsina immunoprotector with adverse effects on the body of environmental and industrial chemical factors that form the secondary immunodeficiency.

Morphological manifestations for the protective effect of miliacin in organs of immunogenesis after treatment with methotrexate.

Morphological changes in lymphoid organs induced by antitumor drug methotrexate were studied in 219 male (CBAxC57B1/6)F1 mice. Plant triterpenoid miliacin attenuated the lymphotoxic effect of this drug.

Triterpenoid miliacin inhibits stress-induced lipid peroxidation.

A plant triterpenoid miliacin prevented stress-induced activation of LPO and accumulation of LPO products in the blood. The inhibitory effect of miliacin was not related to direct inhibition of reactive oxygen species generation.

Effect of naloxone hydrochloride on osteogenesis in chick embryos.

Naloxone hydrochloride, an opioid receptors blocker, was administered to chick embryos. Morphological analysis of femoral bones of embryos showed an appreciable increase in the thickness of the perichondral bone cuff in the tubular bone diaphyses and increased mitotic activity in the zone of proliferating young cartilage of the epiphyseal plate.

Effect of the triterpenoid miliacin on the sensitivity of lymphocytes in the thymus and spleen to dexamethasone-induced apoptosis.

We studied the effect of plant triterpenoid miliacin on dexamethasone-induced apoptosis in thymocytes and splenocytes. Miliacin produced a protective effect on splenocytes by decreasing the degree of DNA fragmentation due to blockade of the cascade cell death distally to the intramembrane phosphatidylserine translocation.

[The role of the liver macrophage system in decreasing the immune complex level of the blood during adaptation to periodic hypoxia]. / Rol' makrofal'noi sistemy pecheni v snizhenii soderzhaniia immunnykh kompleksov v krovi pri adaptatsii k periodicheskoi gipoksii.

It has been established that adaptation to intermittent hypoxia in altitude chamber considerably increases the capacity of hepatic macrophagal systems (MFS) to uptake Indian ink particles from the blood as well as immunoglobulin labelled with fluorescein isothiocyanate. There is simultaneous catabolism of labelled albumin in hepatic MFS. It has been suggested that the increased C3b-component of complement system in blood observed in adaptation to hypoxia plays a substantial role in the activation of hepatic MFS. The role of hepatic MFS activation in reducing the number of circulating immune complexes is emphasized as well as its role in therapeutic effect of adaptation in allergic diseases.

[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 effect of adaptation to the periodic action of hypoxia on the indices of the immunity system and on the course of allergic diseases]. / Vliianie adaptatsii k periodicheskomu deistviiu gipoksii na pokazateli sistemy immuniteta i techenie nekotorykh allergicheskikh zabolevanii.

The authors studied the effect of adaptation to periodical exposure to hypoxia on the organism's immune status and the values of neurohumoral regulation in children with bronchial asthma and adults suffering from allergic dermatoses and autoimmune thyroiditis. It was found that adaptation facilitated normalization of humoral values of immunity in allergic and autoimmune disorders (the content of serum immunoglobulins increased while the level of circulating immune complexes reduced) and was attended by a stable therapeutic effect. The revealed changes of the immune values occurred in increase of the reserve potency of the hypothalamo-hypophyseal-adrenal and sympathoadrenal systems and reduction of the blood histamine level.

[Determination of liver cholesterol-7 alpha-monooxygenase activity in an in vivo experiment]. / Opredelenie aktivnosti kholesterol-7 al'fa-monooksigenazy pecheni v éksperimente in vivo.

The method of determination of cholesterol-7 alpha-monooxygenase activity in vivo which has a number of advantages over the existing ones is offered. [3H]cholesterin was injected into rats intravenously in the form of albumin-stabilized emulsion. In 2--4 h and then every day 3H2O radioactivity of one of the cholesterin enzymatic hydroxylation products in microsomal liver apparatus was estimated in animals' urine. The dynamics of 3H2O secretion during 7 days and dependence of the urine radioactivity upon the given radionuclide dose are shown.

[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.