[Induction of synthesis and activation of Penicillium commune alpha-L-rhamnosidase].

For the first time the influence of a number of synthetic porfirin and fluoren derivatives, coordinative germanium substances and surfactants on the biosynthesis and activity of Penicillium commune 266 alpha-L-rhamnosidase has been studied. It is shown that some of porfirin derivatives and coordinative germanium substances may be used as inducers of biosynthesis (143-430%) and also as stimulators of alpha-L-rhamnosidase activity (15-44%). It is more expedient to use biscitratgermanium acid in a complex with asparaginic acid (430%) or threonine (370%) as inducers of biosynthesis of enzyme. At the same time the use of porfirin derivatives, in particular meso-tetra(N-methyl-6-chinoline)porfirin tosilate or its manganese complex, is more efficient as stimulators (40%) of alpha-L-rhamnosidase activity. The utilization of such surfactants as tregaloso-, peptido- and rhamnolipids is not expedient. These compounds either do not influence or inhibit biosynthesis and activity of P. commune alpha-L-rhamnosidase. Only in concentration of 0.01% rhamnolipid increased the activity of enzyme by 7.5%.

[Influence lactobacilli on the functional activity of macrophages and delayed hypersensitivity reaction in mice]. / Vplyv laktobatsyl na funktsional'nu aktyvnist' makrofahiv ta reaktsiiu hiperchutlyvosti spovil'nenoho typu u myshei.

The influence of the genus Lactobacillus strains on the macrophages' functional activity and intensity of the delayed hypersensitivity reaction in mice has been studied. It has been shown that lactobacilli take positive effect on the cell-mediated mechanisms of the organisms' non-specific resistance and do not intensify the proceeding of specific immune reaction. The strain Lactobacillus fermentum ATCC 14931 is promising as the basis for the immunomodulatory probiotic preparation.

[Biochemical mechanisms of realization of antiviral and interferon-inducing activity of amixine and its analogs]. / Biokhimicheskie mekhanizmy realizatsii protivovirusnoi i interferonindutsiruiushchei aktivnosti amiksina i ego analogov.

Antiviral and interferon inducing activity of the amixine and its some derivatives, as well as their influence on the proteolytic enzymes activity, monooxygenase activity of the microsomal fraction, level of the lipids peroxidation were studied. Lack of correlation between antiviral and interferon inducing activity in the investigated series of compounds was found. Vice versa, the good correlation between interferon inducing activity and the elastase-like activities inhibition ability of the compounds was observed. It allows to state the assumption, that only one ability of compounds to induce of an interferon doesn't suffice for obtaining of high titres of interferon, and while their rather high antiproteolitic activity is necessary. It's shown, that except for one compound the influence of amixine and its derivatives on the red-ox enzymes activity well correlates with their ability to the interferon-inducing. All presented above allows to attribute amixine and its derivatives to polymodal antiviral agents.

[Effect of enomelanin on lipid peroxidation and the glutathione system in rat lung tissue exposed to NO2]. / Vliianie 'enomelanina na perekisnoe okislenie lipidov i sistemu glutationa v legochnoi tkani krys pri deistvii NO2.

Effect of preliminary intraperitoneal injection on the state of the glutathione system and lipid peroxidation intensity in the lungs of rats subjected to NO2 has been studient. This compound is shown to decrease significantly all lipid peroxidation processes and to inhibit completely glutathion oxidation. These effects are supposed to be a result not only of antioxidant properties of enomelanin, but also of its ability to promote a decrease in the activity of glutathione-depending enzymes subjected to NO2.

[Anti-edematous action of EDTA, its effect on lipid peroxidation intensity and various components of the antioxidant system of the lungs in rats exposed to NO2]. / Protivootechnoe deistvie EDTA i ee vliianie na intensivnost' perekisnogo okisleniia lipidov i nekotorye komponenty antioksidantnoi sistemy legkikh krys pri vozdeistvii NO2.

It has been studied how preventive administration of EDTA influences toxic NO2- induced pulmonary edema and disturbances in antioxidant systems. The compound in question, being preventively administered, has exerted a significant antiedematic effect as a result of a decrease in lipid peroxidation intensity and protection of the most important substrate components of the nonenzymatic antioxidant system from the oxidation effect.

[The effect of tilorone on peroxidation systems and antiperoxidation defense under normal conditions and in hypoxia]. / Vliianie tilorona na sistemy perekisnogo okisleniia i antiperekisnoi zashchity v norme i pri gipoksii.

Modifying effects of widely used immunomodulator tylorone on lipid peroxidation and the state of antioxidant system were studied under conditions of normal state as well as in subacute poisoning with carbon monooxide. Multiple effects of tylorone on these reactions were found in various tissues. The drug increased content of reduced glutathione in liver tissue, while amount of the substance was decreased in kidney and heart muscle. Content of diene conjugates and of SH-groups in blood, content of ascorbate in adrenal glands and activity of glucose-6-phosphate dehydrogenase in liver tissue were found to decrease. After administration of tylorone alterations of the most patterns studied under hypoxic conditions were similar to those of normal state. At the same time, the oppositely directed alterations were detected in content of reduced glutathione in heart muscle and in activity of glucose-6-phosphate dehydrogenase in liver tissue under conditions of carbon monoxide poisoning.

[Mechanisms in the modulation of the reactions of immune splenocytes by macroheterocyclic compounds]. / Izuchenie mekhanizmov moduliatsii reaktsii immunnykh splenotsitov makrogeterotsiklicheskimi soedineniiami.

The effect of macroheterocyclic compounds possessing immunostimulating properties in vivo on the reactions of the immune splenocytes in vitro has been studied. It has been shown that the cell activity is determined by the medium ionic composition. In the medium with the optimal content of the bivalent cations the azacrown ethers decrease the intensity of the immune splenocytes reactions depending on the dose. In the media of the modified ionic composition the studied compounds in concentration 10 microM activate all the reactions of the spleen cells, in concentration 100 microM they suppress or do not change them.

[Tetraphenylporphyrin-Sn4+ induction of cytochrome P-450]. / Induktsiia tetrafenilporfirinom-Sn4+ tsitokhroma P-450.

TPP-Sn4+ was administered intraperitoneally (25 mg/kg body weight). The study was performed for 1-30 days. A day after administration the increase in the hemoprotein level 1.4 times was observed, as well as an increase in the level of p-hydroxylation of aniline. On 7-14 days the greatest increase in cytochrome P-450 content was observed. To clarity the mechanism of TPP-Sn4+ effect on cytochrome P-450, we studied its effect on the activity of heme oxygenase and LP rate. This compound is an inhibitor of heme oxygenase activity and reduces the rate of LP in the microsomes which regulates porphyrin metabolism in the organism.

[Characteristic features of 35S-benzoylthiamine monophosphate in albino mice]. / Osobennosti raspredeleniia 35S-benzoiltiaminmonofosfata v organizme belykh myshei.

Equimolar doses (30 mM/kg) of 35S-labelled thiamin, thiamin monophosphate or benzoyl thiamin monophosphate were administered intraperitoneally into mice. Increase in content of labelled metabolites, derived from 35S-benzoyl thiamin monophosphate, as compared with 35S-thiamin and 35S-thiamin monophosphate, was more distinct and prolonged in mice tissues, especially in brain and heart muscle, within 6-24 hrs. In blood this relationship was opposite. Total 35S was excreted with urine also at the highest rate after the 35S-benzoyl thiamin monophosphate administration as compared with the effect of thiamin and thiamin monophosphate but differences between the experimental data obtained with the latter compounds were only slight.

[Catalytic properties of monooxygenases from isolated immunocompetent cells]. / Kataliticheskie svoistva monooksigenaz izolirovannykh immunokompetentnykh kletok.

The kinetic parameters of two monoxygenase (N-demethylase and benzo(a)pyrene hydroxylase) reactions occurring in murine immunocompetent cells were determined. It was shown that the pH optimum for macrophage enzymes lies at 7.4, whereas that for thymocytes and spleen cells at 8.5. The effects of cytochrome P-450 inhibitors (methyrapone, SKF-525A, tilorone) on monooxygenase systems of immunocytes were investigated. Methyrapone and SKF-525A were shown to be effective inhibitors of N-demethylase. The mode of inhibition changes from non-competitive to competitive, depending on the inhibitor concentration. Tilorone, an immunostimulator and inhibitor of liver cytochrome P-450-dependent enzymes, competitively inhibits N-demethylase and benzo(a)pyrene hydroxylase of immunocytes.

[Phytohemagglutinin--a modulator of activity of cytochrome P-450-dependent enzymes of hepatocyte and immunocyte membranes]. / Fitogemaggliutinin--moduliator aktivnosti tsitokhrom P-450-zavisimykh fermentov membran gepatotsitov i immunotsitov.

The phytohemagglutinin effect in vivo on monooxygenase activity depends on the type of the cells under study (thymocytes, splenocytes, macrophages, hepatocytes) and on the period after lectin injection. Variations of monooxygenase activities associated with different forms of cytochrome P-450 are established to have a number of peculiarities in isolated hepatocytes as compared to those in the liver microsome fraction. These differences are supposed to be due to the effect of nonmicrosomal cytochrome P-450. The results obtained are discussed with regard for phytohemagglutinin effect on systems regulating activity of cytochrome P-450-dependent monooxygenases.

[Changes in the activity of flavoprotein-dependent monooxygenase of immunocompetent cells in the mouse in response to antigens and low-molecular immunomodulators]. / Izmenenie aktivnosti flavoproteid-zavisimoi monooksigenazy immunokompetentnykh kletok myshei pod vliianiem antigena i nizkomolekuliarnykh immunomoduliatorov.

The activity of flavoproteid-dependent monooxigenase (benzpyrene-3-monooxigenase) in thymocytes, splenocytes and macrophages was studied in dynamics of development of the immune response to ram erythrocytes and with administration of low-molecular immunodepressants and immune stimulators to mice. It is shown that primary and secondary immunizations decrease the enzyme activity in splenocytes and macrophages. In the thymus cells it grows thrice as high a day after the antigen administration and then lowers. It is supposed that stimulation at the initial stages of the monooxigenase activity in the thymus and its inhibition in splenocytes and macrophages are main stages in development of the immune response. The data obtained are discussed accounting for cytochrome P-450 participation in metabolism of endogenic steroids and prostaglandins which are immunogenesis regulators.

[Changes in the monooxygenase activity of the mouse liver by the activity of high-molecular immunomodulators]. / Izmenenie fermentativnoi aktivnosti monooksigenaz pecheni myshei pri vozdeistvii vysokomolekuliarnykh immunomoduliatorov.

Activity of mice hepatocyte monooxygenases was studied in dynamics of immune response to administration of sheep erythrocytes and phytohemagglutinin. During the primary and secondary immune response the antigen inhibited activity of cytochrome P-450-dependent reactions (N-demethylase and p-hydroxylase), which was apparently due to synthesis of interferon. At the same time, activity of cytochrome P-448-dependent system (benz-alpha-pyrene hydroxylase) was 1.5-5-fold increased as compared with controls as a result apparently of its participation in synthesis of immunoregulators.

[Benzo(a)pyrene hydroxylase activity of immunocompetent cells]. / Benz(a)pirengidroksilaznaia aktivnost' immunokompetentnykh kletok.

A study was made of aryl hydrocarbon hydroxylase activity in immunocompetent cells of varying origin and in hepatocytes from CBA mice. The cells from intact animals may be arranged in the following way with regard to the activity of the enzyme: macrophages greater than hepatocytes much greater than thymocytes greater than splenocytes. The immunostimulants (tilorone and its analogs) altered benzo(a)pyrene hydroxylase activity depending on the cell type.

[Changes in the enzymic activity of monooxygenase components of rat hepatocytes after administration of tilorone]. / Izmenenie fermentativnoi aktivnosti komponentov monooksigenaz gepatotsitov krys pri vvedenii tilorona.

It is established that tilorone-hydrochloride, the antiviral agent, stimulating the interferon synthesis in the organism of animals under experiment inhibits monooxygenase reactions in the albino rat hepatocytes being administered in combination with phenobarbital and 20-methylcholanthrene. The tilorone effect on the N- and O-demethylase activity of the liver microsomes in vitro was studied. It is established that the rate of dimethylaniline N-demethylation and anisole O-demethylation in this case lowers considerably, the character of the kinetic curves being unchanged.