[Immunosupressive effect of hypokinetic stress and sensitization of thymus to glucocorticoids].

24-hour hypokinetic stress expressed in decrease of sensitivity of cellular and humoral immu nity to subsequent immunization with sheep erythrocytes was studied. The development of this phenomenon is associated with sensitization of lymphoid tissue to hypoplasia effect of glycocorticoid hormones. In introduction of glycocorticoid stress, the animals revealed a more pronounced depression of proliferative activity of thymocytes compared with non stressed animals.

[Influence repeated stress on immune responciveness and monooxigenase activity of normotensive and hypertensive rats].

Repeated stress led to antipodal directions in immune system and cytochrome P450 activities of normotensive and hypertensive rats. Enhancement of the Reaction of Delayed Hypersensitivity, suppression of cytochrome P450-mediated monooxigenase activities were observed in Wistar rats. On the contrary, in the NISAG decrease of the Reaction Delayed Hypersensitivity, elevation of cytochrome P450-mediated monooxigenase activities were observed, as comparison with Wistar rats.

[The effect of ladasten on the activation-induced expression of Fas receptor on T-lymphocytes and their sensitivity to Fas-induced apoptosis]. / Vliianie Ladastena na aktivatsionno-indutsirovannuiu ékspressiiu Fas-retseptora na T-limfotsitakh i ikh chustvitel'nost' k Fas-indutsirovannomu apoptozu.

The effects of ladasten on the activation-induced expression of Fas-receptor on T-lymphocytes, their sensitivity to Fas-induced apoptosis, and the expression of mitogen-activated ERKI/ERK2 protein kinases have been studied. In the range of concentrations 0.1-10 microM, ladasten exhibited a comitogenic effect on the TCR-mediated stimulation of T-lymhocytes ion the peripheral human blood, which was accompanied by an increase in the level of phosphorylated form of ERK-2. At the same time, ladasten virtually did not change the activation-induced expression of Fas-receptor on T-lymphocytes, but reduced the rate of the Fas-induced apoptosis. It was concluded that the immunoprotective effect of ladasten is probably based on a decrease in the rate of Fas-induced apoptosis.

[Insertional polymorphism of the CYP2E1 gene in infiltrative pulmonary tuberculosis in populations of Bashkortostan Republic]. / Insertsionnyi polimorfizm gena CYP2E1 u bol'nykh infil'trativnym tuberkulezom legkikh i v populiatsiiakh respubliki Bashkortostan.

Insertion polymorphism Ins96 of the CYP2E1 promoter region was for the first time studied in three ethnic groups of Bashkortostan. Population-specific features of genotype and allele frequency distributions were observed. The CYP2E1 polymorphism was associated with infiltrative pulmonary tuberculosis in the Bashkortostan population.

[The effect of recombinant interleukin 1beta on cytochrome P-450 dependent monooxygenases in rat liver and kidney]. / Vliianie rekombinantnogo interleikina-1 beta (rIL-1 beta, Betaleikin) na tsitokhrom P-450-zavisimye monooxidazy pecheni i pochek u krys.

Effects of a single administration of the human recombinant interleukin 1beta (rIL-1beta, betaleukin) on the cytochrome P-450 dependent monooxygenase activity in rat liver and kidney were evaluated in intact rats and on the background of cytochrome P-450 inductors. It was found that betaleukin suppressed the CYP1A1/2-dependent ethoxyresorufin-o-deethylase activity in both liver and kidney, as well as the CYP2C-dependent dibenzylfluorescein-debenzylase and CYP2E1-dependent nitrophenol-hydroxylase activity in liver, but induced CYP3A-dependent N-demethylation of erythromycin in liver and kidney. Betaleukin also inhibited the beta-naphthoflavone-induced monooxygenase activity in liver, while only insignificantly acted upon the induced monooxygenases in kidney. Betaleukin decreased the pyridine-induced CYP2E1-dependent monooxygenation in liver and CYP1A1/2-dependent monooxygenation in kidney. Therefore, the character and direction of the influence of rIL-1beta on cytochrome P450 belonging to various subfamilies are variable and tissue-specific.

[Polymorphism of the tumor necrosis factor alpha gene in patients with infiltrative tuberculosis and from the Bashkorstan populations]. / Polimorfizm gena faktora nekroza opukholei alpha u bol'nykh infil'trativnym tuberkulezom legkikh i v populiatsiiakh Bashkorstana.

The polymorphism at position -308 of the TNF-alpha gene promoter was analyzed in three ethnic groups and in patients with infiltrative pulmonary tuberculosis from Bashkortostan. No interethnic difference in allele or genotype frequency distribution was observed. The frequency of allele TNF2 in tuberculosis patients was significantly higher than in controls (chi 2 = 11.69, p = 0.001), suggesting an association of this allele with higher risk of pulmonary tuberculosis or a disturbed immune response.

[Effect of bemethyl on cytochrome P-450-dependent monoxygenases in the human liver and lymphocytes]. / Vliianie bemitila na tsitokhrom P-450-zavisimye monoksigenazy v pecheni krys i limfotsitakh cheloveka.

Effects of the actoprotector bemithyl (50 mg/kg, p.o.) upon a single or five-fold administration on the cytochrome P-450 and b5 content and the isoform-specific and nonspecific monooxygenase activity [aminopyrine-N-demethylase, aniline-p-hydroxylase, 4-nitroanisole-o-demethylase,2,5-diphenyloxazole-p-hydroxylase, 7-ethoxyresorufin-o-deethylase (EROD), benzyloxyresorufin-o-debenzylase (BROD)] in rat liver were evaluated. In addition, the influence of bemithyl (0.(1)-100 microM) on the development of EROD and BROD activity was studied on the mitogen-stimulated human lymphocytes in vitro. Administered in rats, bemithyl exhibited the properties of a cytochrome P-450 inductor of the mixed type, which was manifested by an increase in the total cytochrome P-450 content in liver microsomes and in the monooxygenase activity related to both Ah-receptor-dependent and -independent isoforms (except for the aniline-p-hydroxylase activity). The induction of the monooxygenase activity realized by Ah-receptor-dependent isoforms (4-nitroanisole-o-demethylase, 2,5-diphenyloxazole-p-hydroxylase, and EROD activity) was more pronounced, reaching maximum upon a single drug administration. Acting upon the human lymphocytes in vitro, high concentrations of bemithyl increased expression of the EROD activity, while low drug concentrations stimulated the BROD activity.

[Phenomenon of apoptosis in the survival of enterobacteria in the parasite-host system]. / Fenomen apoptoza v vyzhivanii énterobakterii v sisteme parazit-khoziain.

Data on the apoptosis phenomenon with enterobacteria used as a model are presented. One of the mechanisms regulating the vital activity of eukaryotic cells is, together with cell proliferation and differentiation, the phenomenon known as "apoptosis". This physiological process of the eukaryotic cells death is used by many parasites in parasite--host relationships in different epitopes. The system known to trigger programmed cell death, is the surface receptor Fas, the receptor of tumor necrosis factor (TNF alpha) activated by the corresponding FasL ligand and TNF alpha, which further triggers the cascade mechanisms of the execution program. In various representatives of enterobateria different proteins serve as Fas ligand, viz. protein IpaB in Shigella flexneri, SipB activating converting enzyme IL-1 beta, identical to capsase-1, in Salmonella spp., YopP in Yersinia spp. Still the mechanism triggering apoptosis in Yersinia spp. has some original features. In Escherichia coli alpha-hemolysin is the factor triggering the suicidal program, the triggering mechanism being mediated by an increase in intracellular calcium ions.

[Effect of ladasten on proliferative activity and apoptosis in peripheral blood T-lymphocytes ]. / Vliianie ladastena na proliferativnuiu aktivnost' i apoptoz T-limfotsitov perifericheskoi krovi.

The effects of ladasten (0.1-10 microM) on the proliferative activity, apoptosis, and expression of the apoptosis protein regulators (bcl-2 and p53) was studied in 72-h cultures of T-lymphocytes of human peripheral blood activated by anti-CD3MCA. In the concentration interval from 0.01 to 1 microM, ladasten produced a comitogenic effect. The drug changed neither the activity of caspase 3 and the proportion of cells in the late apoptosis stage (Hoechst 33342 stain test), nor the bcl-2 expression, but increased the p53 expression in the activated cells. Irrespective of the concentration, ladasten protected activated lymphocytes in the cell culture from apoptosis induced by the topoisomerase I inhibitor camptothecin or by hydrogen peroxide (provided that the drug was added to the culture simultaneously with the apoptosis inductor). At the same time, lymphocytes cultivated in the presence of ladasten acquired resistance with respect to apoptosis induced by hydrogen peroxide, but not by camptothecin. It is suggested that the immunomodulant activity of ladasten are related to the comitogenic effect and the increase in resistance of the activated T-lymphocytes with respect to non-receptor-induced apoptosis.

[Cosmetic results of posttraumatic eyeball subatrophy surgical treatment using "alloplant" biomaterials with subsequent use of prostheses]. / Kosmeticheskie rezul'taty khirurgicheskogo lecheniia posttravmaticheskoi subatrofii glaznogo iabloka s primeneniem biomaterialov "alloplant" i s polseduiushchim protezirovaniem.

A complex of surgical operations making use of Alloplant biomaterials, performed in 47 patients with initial posttraumatic subatrophy and 79 patients with well-developed and far advanced stages of this condition, helped preserve the eye as anatomical organ in 97.5% patients, with enlargement of the eyeball in two-thirds of patients and stabilization in one-third. Optic reconstructive operations were later performed and visual acuity improved in patients with the initial stage of subatrophy. Use of allotransplant for eyeball bandage in order to create a carcass for the sclera helped conceal the cicatricial deformation of the sclera and repair the shape and volume of the eyeball in patients with initial subatrophy, due to which a good cosmetic result was attained. In well-developed and far advanced subatrophy use of biomaterial for bandage created optimal conditions for thin-wall cosmetic prostheses, ruled out the irritating effect of the prosthesis in cases when corneal sensitivity was retained and/or there were coarse corneaoscleral cicatrices, and thus extended the indications for cosmetic prostheses of subatrophic eyes.

[The effect of aqueous extracts of hepatotropic medicinal plants on free-radical oxidation processes]. / Vliianie vodnykh izvlechenii iz nekotorykh gepatotropnykh lekarstvennykh rastenii na protsessy svobodnoradikal'nogo okisleniia.

The authors studied the effect of decoctions and infusions of medicinal plants (common barberry, sandy immortelle, common maize, spotted milk thistle) on free-radical oxidation (FRO) in model systems in vitro and in experiments in vivo on nonbred albino mice. In various model systems (in which active forms of oxygen are generated and lipid peroxidation takes place) the plants under study suppressed as well as intensified the processes of lipid peroxidation, depending on the concentration of the phytopreparation and the type of the model systems. In in vivo experiments the drugs of plant origin suppressed lipid peroxidation, reducing the parameters induced by iron and chemoluminescence and the malonic dialdehyde level in the liver.

[Effect of rifampicin, endotoxin, and their combination on the phagocyte activity, microsomal oxidation, and free radical processes in the liver]. / Vliianie rifampitsina, éndotoxina i ikh kombinatsii na aktivnost' fagotsitov, mikrosomal'noe okislenie i svobodno-radikal'nye protsessy v pecheni.

Experiments were conducted on mices to study the effect of strain MRe-600 Escherichia coli endotoxin, rifampicin, and their combination at the level of cytochrome p-450, b5, aminopyrine N-demethylase and aniline-r-hydroxylase activity in the liver, absorptive activity and oxygen dependent metabolism of macrophages, and free-radical processes in the liver. It was found that rifampicin removes the endotoxin-induced depression of microsomal oxidation in the liver, but potentiates the stimulating effect of the endotoxin on macrophageal absorptive activity and the "respiratory outburst" in these cells. The oxidative equilibrium in the liver in this case does not change.

[The immunotropic properties of biologically active products obtained from Klamath weed (Hypericum perforatum L.)]. / Immunotropnye svoistva biologicheski aktivnykh produktov, poluchennykh iz zveroboia prodyriavlennogo.

We carried out a systematic study of immunotropic activity of John's wort on the level of integrated fractions including all basic active substances of this plant. Both types of substances capable of increasing and suppressing the immunity were found in John's wort. Polyphenol fraction exhibits the immunostimulating activity with respect to the system of mononuclear phagocyte system, cellular and humoral immunity, and is capable of recovering the immune response in conditions of high-zone tolerance. Lipophilic fraction of this plant exhibits immunosuppressing properties with respect to cellular and humoral immune response. Immunotropic activity of polyphenol and lipophilic fractions correlate with their low toxicity.

[Prodigiozan modulation of the specific activity of antidepressants]. / Moduliatsiia prodigiozanom spetsificheskoi aktivnosti antidepressantov.

The experiments carried out on mongrel male mice showed that bacterial lipopolysaccharide Prodigiozan inhibit the activity of P-450-dependent monooxygenases of the liver, thus changing the activity of antidepressants--amitriptyline and imipraminum. The data on biological activity were tested in "tail suspension" test. Prodigiozan exhibited no central effect. Changes in biotransformation processes after single administration of both drugs resulted in the delay and prolongation of the effect. Prodigiozan prevents the induction of microsomal enzymes caused by antidepressants. Amitriptyline do not affect the immunostimulating action of prodigiozan, whereas imipraminum inhibited prodigiozan activity.

[The interaction of the immune system and the liver mono-oxygenase system]. / K voprosu o vzaimodeistvii immunnoi sistemy i monooksigenaznoi sistemy pecheni.

The effect of different immunostimulants (prodigiosan, levamisole, T-activin, sodium diethyl dithiocarbamate, sodium nucleinate, lithium chloride, muramil dipeptide, B-activin) and mixed hepatic function oxidase inhibitors (cimetidine, chloramphenicol) or inducers (phenobarbital, flumecinol, rifampicin) on immune reactivity (macrophage function, humoral and cellular responses) and hepatic microsomal function (hexobarbital sleeping-time) was studied in non-inbred and BALB/c male mice. There was a high correlation between the ability of immunostimulants to depress hexobarbital metabolism and their ability to enhance macrophage activity (carbon clearance test), but not humoral and cellular immunity. No reciprocal changes occurred in immune reactivity after positive or negative pharmacological modulation of hepatic drug metabolizing enzyme activity.

[The pharmacokinetic and immunopharmacological aspects of prodigiozan interaction with psychotropic agents]. / Farmakokineticheskie i immunofarmakologicheskie aspekty vzaimodeistviia prodigiozana s psikhotropnymi sredstvami.

In experiments on white male mice it was found that an immunostimulant prodigiozan suppresses the activity of cytochrome P-450-dependent liver monohygenases that results in modulation of the activity of neuroleptics (aminazine and haloperidol) administered against its background. Their activity is assessed by the "open field "test" and the "tail suspension test". One could observe a delay of the occurrence of the neuroleptics' effect and prolongation of the effect. Acute toxicity of aminazine was shown to decrease. The changes are most probably due to a slowing of metabolism of the neuroleptics in the liver. On the other hand, administration of neuroleptics against the background of prodigiozan fails to affect its immunostimulating effect despite diverse influences of the drugs on the activity of the liver monooxygenase.

[Immunostimulants and autoimmunity]. / Immunostimuliatory i autoimmunitet.

The review presents the recent data on the use of immunity stimulants (thymus peptides, synthetic immunomodulators, immunostimulants of bacterial origin) under conditions of experimental autoimmunity and in clinic. A brief characteristic of the immunotropic activity of the drugs is given, the mechanisms of their action on the formation of the autoimmune response and clinical effectiveness are analyzed.