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Biomedical subjects

I A Shchepetkin

Publications and source records attributed to I A Shchepetkin.

At least 19 recordsLinked to original sources
PubMed2003

[Effect of sanazole and metrinidazole on production of reactive oxygen species by macrophages].

The in vitro effect of sanazole (AK-2123; N-(2'-methoxyethyl)-2-[3"-nitro-1"-triazolyl]acetamide) and metronidazole (1-beta-hydroxyethyl-2-methyl-5-nitroimidazole) on phorbol-12-myristate-13-acetate (PMA)-stimulated and spontaneous (without stimulation by PMA) production of reactive oxygen species (ROS) by peritoneal and splenic murine macrophages was studied. ROS production was analyzed using fluorescent probe 2',7'-dichlorofluoresceine diacetate (DCFH-DA). An increase in the spontaneous production of ROS by macrophagal cells with therapeutic concentration of sanazole (0.6-1.25 mM) in the incubation medium was observed. At these concentrations metronidazole had no effect on spontaneous production of ROS by macrophagal cells. PMA-stimulated ROS production was inhibited by high concentrations (2.5-10 mM) of sanazole and metronidazole. The spontaneous generation of ROS by peritoneal macrophages was stimulated by sanazole at all tested concentrations (0.6-10 mM).

Adjuvants, Immunologic↗
PubMed2000

[The comparative biochemical and morphological characteristics of chondrosarcoma and giant-cell tumor of the bone].

Spectrometry has been employed to assess the levels of collagenase, catepsin D, trypsin-like proteinases and their inhibitors as well as bone acid and alkaline phosphatase both in the center and along the periphery of giant cell tumor of bone (GCTB) and chondrosarcoma. The levels of collagenase, trypsin-like proteinases and their inhibitors in the center of chondrosarcoma were much higher while those of alkaline phosphatase--lower than along tumor periphery. The catepsin D and acid phosphatase concentrations of the center and periphery of chondrosarcoma were similar. It was suggested that an extremely low concentration of trypsin-like inhibitors may contribute to degradation of the matrix in tissues adjacent to chondrosarcoma and, consequently, to tumor invasion development.

Acid Phosphatase↗
PubMed2000

[Indices of proteolysis in evaluation of resorption in bone tumors].

Activities of acid and alkaline phosphatases, collagenase, cathepsin D, trypsin-like proteinases, alpha(1)-proteinase inhibitor (alpha(1)-PI), alpha(2)-macroglobulin (alpha(2)-MG) were measured in blood plasma and tumor tissue of patients with giant-cell tumor of the bone (GCTB) and bone chondrosarcoma. These tumors differed by enzymatic activities. GCTB is characterized by increased activity of alkaline phosphatase, while in chondrosarcoma tissue the activities of collagenase and cathepsin D were the highest. Activities of acid phosphatase, collagenase, trypsin-like proteinases were increased in the plasma of patients with both tumors; alpha(1)-PI/alpha(2)-MG ratio was increased. Bone resorption parameters correlated with proteolysis inhibitors. Activities of collagenase and acid phosphatase were increased in tumor tissue and plasma in the presence of low activities of alpha(2)-MG and increased alpha(1)-PI/alpha(2)-MG index, which seems to require special attention during the postoperative period.

Adolescent↗
PubMed1998

[Effect of metronidazole on luminol dependent chemiluminescence of neutrophils in whole blood of patients with chlamydial infection].

In vivo effect of metronidazole on the active oxygen production by neutrophils in the peripheral blood of patients with urogenital chlamydial infection (9 females and 7 males) was studied with the use of luminol dependent chemiluminescence. Metronidazole was administered orally in a dose of 250 mg twice a day for 10 days. Blood for the specimens was collected prior to the treatment and on the next day of the treatment course completion. No effect on the spontaneous and zymozan or phorbol-12-myristate-13-acetate stimulated chemiluminescence was observed, although a significant increase in the chemiluminescence indices was stated in 3 females and 1 male. It was suggested that the changes in the individual values of the neutrophil chemiluminescence after the treatment were associated with the influence of metronidazole and/or its metabolites on the blood cells and with different activity of the host enzymes participating in the drug biotransformation.

Administration, Oral↗
PubMed1998

Generation of sanazole nitro radicals by xanthine oxidase.

The formation of sanazole (drug AK-2123) radicals by the xanthine--xanthine oxidase system was studied by spectrophotometry in hypoxygenic (pO2 = 45 +/- 5 mm Hg) and normoxygenic (pO2 = 150 +/- 4 mm Hg) media. At concentrations from 0.1 to 10.5 mM, sanazole dose-dependently increased the rate of cytochrome c reduction in hypoxygenic medium but had no effect on the reaction rate under normoxygenic conditions. The activating influence of sanazole depended on xanthine concentration. At xanthine concentrations from 0.08 to 0.1 mM in hypoxygenic medium, the rate of cytochrome c reduction was increased twofold after the addition of sanazole. Reduction of cytochrome c in the medium without sanazole was completely blocked by superoxide dismutase; addition of sanazole partially restored the blocked reaction. Cytochrome c reduced in the presence of superoxide dismutase and sanazole was oxidized by cytochrome oxidase. The data indicate that in the presence of the xanthine--xanthine oxidase system under hypoxygenic conditions, sanazole can accept electrons and generate nitro radicals which donate electrons to cytochrome c or oxygen.

Animals↗
PubMed1997

[Metronidazole effect on active oxygen production by human blood neutrophils].

The in vitro effect of metronidazole on production of active oxygen by neutrophila and in the enzymatic system of glucose-glucose oxidase-peroxidase was studied by luminol-dependent chemiluminescence. An increase in the spontaneous and zymozan-stimulated chemiluminescence and a decrease in the phorbolmyristate acetate (PMA)-stimulated chemiluminescence after 2-hour preincubation of the neutrophils with 8.5 mM of metronidazole were observed. In concentrations of 0.9 to 8.7 mM metronidazole (without washing) dose-dependently lowered the neutrophil chemiluminescence in response to the effect of PMA and ionophore A23187 and to a lesser degree to that of zymozan. In doses of 20 to 100 mM the drug had an insignificant effect on production of active oxygen by the neutrophils in response to the cell stimulation by PMA, ionophore A23187 and zymozan. The data are in conformity with the scavenger effect of metronidazole on active oxygen radicals generating in the cell-free enzymatic system both in the presence and in the absence of superoxide dismutase.

Antitrichomonal Agents↗
PubMed1992

[The oxidative metabolism of the blood neutrophilic granulocytes in precancer and cancer of the stomach].

The results of investigation of blood polymorphonuclear leukocytes oxidative metabolism by nitroblue tetrazolium (NBT) test and luminol-dependent chemiluminescence in patients with gastric precancer and cancer are presented. Chemiluminescence was increased in the patients of both groups as compared with control. Disturbances in oxidative metabolism of neutrophils was detectable by NBT test when functional test was used.

Female↗
PubMed1989

[High activity of antioxidant enzymes in a tumor as a factor of "avoidance of control" in the immune system].

The enzymes that utilize H2O2 and lipoperoxides as well as the enzymes of the bioregeneration system glutathione and NADP+ have been examined for activity in the superficial and deep regions of DMBA-induced rat fibrosarcoma and the adjoining skeletal muscle. The activities shown by catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and glucoso-6-phosphate dehydrogenase were 2-3 times higher and reduced glutathione levels were lower in the superficial than in deep areas. The high antioxidant potential of the tumor superficial areas is proposed to be due to the oxygen-dependent mechanisms by which macrophages and neutrophils select tumor cell clones by the given sign.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

[Participation of lipid peroxidation in complement-mediated hemolysis].

Activation of lipid peroxidation (LPO) was recorded during complement-mediated erythrocyte cytolysis. It preceded hemoglobin release and was, presumably, the reason for pore formation in cell membranes. Correlation between the formation of Schiff bases and the decrease in malondialdehyde concentration is suggested.

Animals↗
PubMedDate not supplied

[Hypoxic bioreductive agents: the possible immune and receptor-mediated mechanisms of antitumor action].

The article discusses the possible mechanisms of the antineoplastic effect of hypoxic bioreducing agents (HBA) when they are used in low nonhypoxic doses. Experimental and clinical studies provide evidence of the occurrence of stages which in administration of HBA into the organisms of the tumor-carrier may develop in succession, leading to stimulation of antineoplastic immunity: GBA activation in the hypoxic neoplastic tissue, conjugation of HBA metabolites with the macromolecules of the tumor cells, and presentation of the epitopes of neoantigens in association with the main complex of class I histocompatibility (MCH) cytolysis of these cells by T-killers. This process may be similar to that in contact sensitivity to low-molecular compounds (a variant of the reaction of delayed hypersensitivity [DH]) in the neoplastic focus. It is suggested that direct control of the effect of HBA on the immunocompetent and/or tumor cells may occur additively to or synergically with this process as the result of interaction of these compounds with the surface or intracellular receptors. It cannot be excluded that the activated HBA may force the endogenic ligands out of the nucleophilic centers of these receptors and realize receptor-mediated control of gene expression.

Adjuvants, Immunologic↗
PubMedDate not supplied

[Macrophagal polykaryons].

The mechanisms of formation, morphology and functions of macrophagal polykaryons are discussed. These giant multinuclear cells are formed by means of macrophagal cell fusion ("natural hybridization") and specialized on the extra- and intracellular processes of resorption of the foreign body and tissues of the proper organism. The formation of macrophagal polykaryons seems to be one of the possible manifestation of reactive histiocytosis in chronic inflammation and tumor growth. The role of macrophagal polykaryons in such disease as giant cell arteritis, giant cell granuloma and fibrohistiocytic tumors is considered in details. It is proposed that one and the same mechanism of regulations served as a basis of developing of both osteoclastic remodelling of the bone tissue (morphogenetic process) and resorption of the foreign body and tissues of the proper organism in inflammation in the process of evolution.

Animals↗
PubMedDate not supplied

[Geometrical model of spiral-cyclical self-organization of morphofunctional modules with two-dimensional (2D) transfer channels].

The general model of spiral-cyclic self-organization of morphofunctional modules has been studied with the help of elliptic Riemannian geometry. Depending on the level of hierarchy cells, groups of cells, macromolecules or subcellular components can function as separate biological units. The hierarchically coordinated morphofunctional modules of biological pattern with two-dimensional (2D) channels of morphogenes transfer are formed in the process of geometric transformation. The width of 2D channel is regulated by module parameters, whereas the direction of transport is controlled by vector of module electrostatic field. The disturbance of morphogenesis in the model is regarded as a change of reciprocal hierarchically coordinated arrangement of morphofunctional modules that causes branching of 2D channels without general power- and mass transfer. The model can be used for constructing concrete analogies of self-organization of morphofunctional modules in onto- and phylogenesis.

Animals↗
PubMedDate not supplied

[Effect of platinum derivatives on microsomal NADPH-oxidoreductase activity].

The influence of platinum derivatives, cisplatin (cis-diamminedichloroplatinum) and imidazolplatin (cis-diimidazoledichloroplatinum) on the activity of rat liver microsomal NADPH-oxidoreductases was investigated in vitro using spectrophotometrical and chemiluminometrical methods. In the range of concentrations from 1 to 12 microM cisplatin inhibited NADPH-cytochrome c-reductase activity and NADPH/lucigenin-dependent chemiluminescence of microsomes. The 3 microM cisplatin decreased the NADPH-dependent reductase activity by 50%. At concentrations less than 2.5 mM sanazole (drug AK-2123) did not prevent the inhibiting influence of cisplatin on microsomal NADPH-dependent reductases. Imidazolplatin insignificantly inhibited NADPH-reductases. It is concluded that negligible inhibiting effect of imidazolplatin on microsomal NADPH-oxidoreductase allows us to consider this platinum derivative as a promising compound for further experimental trials as anticancer drug with low toxic action on the normal tissues of an organism.

Animals↗
PubMedDate not supplied

[Effect of azole derivatives on lucigenin-dependent microsome chemiluminescence].

Both metronidazole and aminotriazole increased while sanazole (drug AK-2123) decreased the NADPH/lucigenin-dependent chemiluminescence of liver microsomes of phenobarbital-treated rats. Sanazole strongly inhibited the lucigenin-dependent chemiluminescence in the enzyme system of xanthine-xanthine oxidase. Aminotriazole and metronidazole were less potent inhibitors of chemiluminescence less than sanazole. All these azole derivatives did not absorb light in the region of light emission of lucigenin. Both lucigenin and sanazole increased the rate of cytochrome c reduction by microsomes in case of using NADPH as a donor of electrons, whereas no effect of metronidazole and aminotriazole on this rate was found. The sanazole inhibition of lucigenin-dependent chemiluminescence could reflect competition between sanazole and lucigenin for electrons in the active centre of flavin reductases. Thus, microsomal NAD(P)H-reductases can be potentially involved in a bioactivation of sanazole. Lucigenin-dependent chemiluminescence cannot be used for measuring the modulating action of agents on reactive oxygen species production in the microsomes, but it may be used for luminometrical studies of enzyme complex NAD(P)H-reductases/cytochrome P450 in model systems.

Acridines↗