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Biomedical subjects

G V Cherepnev

Publications and source records attributed to G V Cherepnev.

15 recordsLinked to original sources

[Use of systemic immunomodulator xymedone in distructive pulmonary tuberculosis].

The study was undertaken to examine 59 patients with destructive pulmonary tuberculosis who had T-cell dysfunction (loss of CD3+, CD4+, lymphocytes, slightly positive tuberculin test) and augmented IgA and IgG production. Oral Xymedone given in a dose 2.0 g daily for two 2 months in combination with antibacterial therapy abolished lymphopenia, restored CD4+ counts, CD4+/CD3+ ratio, upregulated IgG levels, but did not affect IgA levels. The Xymedone-treated patients developed fewer side effects due to basic antibacterial chemotherapy and showed more rapid culture conversion, resolution of pulmonary infiltration and closure of destructive cavities.

Adjuvants, Immunologic↗

[The immunomodulator ximedon lowers the level of induced DNA damages in bone marrow and peripheral blood cells: the possibilities for immunogenetic correction].

It was established in experiments on albino unbred mice and during treatment of patients with osteomyelitis that 30 mg/kg of ximidon suppresses the formation of micronuclear polychromatophilic erythrocytes found in the bone marrow of mice and peripheral blood of patients with chronic osteomyelitis. The interrelationship of the results obtained with the modulating effect of ximidon on the mitochondrial, thiol, and adenylate cyclase-dependent mechanisms of cell regulation is discussed.

4-Aminobenzoic Acid↗

[Potential role of the antimutagenic effect of xymedone in modification of immunoreactivity].

Effects of the pyrimidine derivatives of xymedone and methyluracil upon the induction of point mutations of the base pair substitution type in the Salmonella/microsome test and the frequency of chromosome aberrations in the lymphocytes of patients with the chronic osteomyelitis diagnosis. Xymedone more effectively than methyluracil inhibited the induction of point mutations by nitrosomethylurea. In the case of the cyclophosphane induced mutagenesis, the two preparations exhibited comparable antimutagen effects. Both xymedone and methyluracil (1.5 g/day, 10 days) reduced the (increased) frequency of chromosomal aberrations in the lymphocytes of patients with the chronic osteomyelitis diagnosis. The anticlastogenic effect of methyluracil vanished 5 days after termination of the 10-day administration course, while xymedone exhibited an afteraction anticlastogenic effect over this period. Interrelation of the antimutagen effect and immunomodulating activity of xymedone is discussed.

Adjuvants, Immunologic↗

[Apoptosis in the nervous system].

Apoptosis (from Greek apoptosis, i.e., falling of leaves) is the phenomenon of programmed cell death, which plays an important role in the normal embryonic development and maintenance of homeostasis of the differentiated tissues of adult organisms. Completion of the apoptosis process is accompanied by specific morphological and biochemical changes in the involved cells. Various disturbances in the control of apoptosis underlie various neurodegenerative diseases, the formation of malignant tumors, autoimmune disturbances, and developmental abnormalities. A deficit of neurotrophic factors leads to apoptosis of neurons. Survival of specific cell populations of neurons is controlled by neurotrophic factors and their combinations. Oncogene bcl-2, a repressor of cell death, belongs to the better studied factors controlling apoptosis. The terminal stages of cell death, including death of neurons, depend on the activation of caspases, specifically caspase-1 (interleukin-1 beta-converting enzyme). Ca2+ and reactive forms of oxygen play an important role in the initiation of apoptosis by changing mitochondrial permeability. Neuregulin, a factor of neuronal origin, is the main controlling factor in apoptosis of Schwann cells, and this process determines the size of their definitive population. Fibroblast growth factor b diminishes apoptosis of Schwann cells in regenerating nerve fibers.

Animals↗

[Xymedon decreases phosphatidylserine membrane expression induced by proapoptogenic deficit of serum growth factors in Jurkat T-cells].

The effect of xymedone, a non-glucoside analog of pyridine nucleosides, on the apoptosis of human CD4+ T cells of the Jurkat line was studied by laser flow cytometry method. Xymedone decreased the membrane expression of phosphatidylserine and suppressed the increase in permeability of the cytoplasmic membrane, thus inhibiting the onset of a degradation stage of the apoptotic cascade. Possible mechanisms of the antiapoptogenic effect of xymedone within the framework of a (cytochrome C/caspase 3)-dependent signal pathway of the apoptosis are discussed.

Apoptosis↗

[Induction of apoptosis of tumor cells by binase].

An induction of apoptosis by RNase from Bacillus intermedius (binase) and its mutants characterized with low catalytic activity (Lys26Ala and His101Glu) in human myelogenic erythroleukemia K562 cells, human lung carcinoma A549 cells and human peripheral blood mononuclear cells was studied. For the first time selective apoptogenic effects of binase toward leukemic blood cells was determined. Neither antiproliferative nor apoptotic effects of binase were detected in normal human peripheral blood mononuclear cells. Formation of low molecular weight oligonucleosomal DNA fragments (less than 50 Kb) which are an early marks of apoptosis was registered in solid tumor cells treated by binase. Using mutant RNases it was shown that decrease of catalytic activity to 2.5% of wild type enzyme activity leads to the loss of apoptogenic properties of enzyme. Selective apoptogenicity of binase found towards malignant cells confirmed that antitumor agents based on bacterial RNases could be considered as an alternative to standard chemotherapeutic drugs.

Amino Acid Substitution↗

[Effect of xymedone on high-voltage-activated Ca2+ currents in pyramidal neurons of the entorhinal cortex].

The effect of xymedon on Ca2+ currents in entorhinal cortex LIII pyramidal neurons was studied using brain slices from 10-17-day old rats, which were analyzed by means of the infrared video assisted whole cell patch clamp recording. The sample slices were superfused with artificial cerebrospinal fluid containing tetrodotoxin, 4-aminopyridine, and tetraethylammonium for the blocking of Na+ and K+ channels, respectively. Xymedone was added to artificial cerebrospinal fluid and to all extracellular solutions. The slices were exposed to different concentrations of xymedone for 3 hours followed by patch-clamp recordings. Control recordings were run with the vehicle. Xymedone in a concentration of 0.01 mM decreased the maximum voltage-dependent Ca2+ current amplitude by 39.8 %, while 1 mM of xymedone inhibited the Ca2+ currents almost completely. The obtained data showed for the first time that xymedone exhibits a calcium channel blocker activity in neurons. Possible neuroprotective mechanisms of xymedone are discussed.

Animals↗

[Mechanisms of pyrimidine derivatives systemic immunomodulating effect].

Experiments on guinea pigs showed that xymedon in a dose of 30 mg/kg stimulates nucleic acid synthesis in thymocytes and increases the blood serum nucleic acid content. Xymedon increased secretion of endogenous DNA by human lymphocytes stimulated with PNA in vitro. The systemic immunotropic mechanisms of pyrimidine derivatives are discussed.

Animals↗

[Effect of pyrimidine derivatives on the regulation of active transport of calcium in the immunocompetent cells].

Experiments with guinea pig immunocompetent cells and nonadherent and adherent mononuclear fractions of the peripheral blood of healthy donors, and patients with rheumatoid arthritis and purulent surgical infection disclosed different levels of Ca(2+)-ATPase activity. Thymectomy in adult guinea pigs led to diminution of activity of the enzyme in all lymphoid organs. The effect of ximedon (30 mg/kg) on Ca(2+)-ATPase activity depended on the thymus and duration of treatment with the drug, and was of a two-phase character.

Animals↗

[The effect of pyrimidine derivatives on the sulfhydryl status of immunocompetent cells in vivo: the interrelationship with Ca2(+)-ATPase and antimutagenic activity].

It was demonstrated in experiments on guinea pigs that a 30 mg/kg dose of ximedon changes the content of SH-groups in immunocompetent cells depending on the duration of drug administration and the organ to which the cells under test belong. Maximum increase of the SH-groups was recorded in the thymocytes. The dynamics of changes in Ca(2+)-ATPase activity repeated the fluctuations in the SH-group content in the splenic and bone marrow cells. In the bone marrow cells of CBA x C57B1 mice 3 mg/kg ximedon suppressed the induction of chromosome aberrations caused by cyclophosphane. The interrelationship of changes in the cell sulfhydryl status with Ca(2+)-ATPase activity and the antimutagenic effect of ximedon is discussed.

Animals↗