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Hepatoprotective properties of a new pyrimidine derivative - L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one, synthesized on the basis Xymedon, were assessed in white rats exposed to CCl4. The compound under study administered prior to exposure to CCl 4 reduced the deviation of biochemical parameters from reference values and severity of structural and morphological changes in liver, when compared to the control. Hepatoprotective properties of the studied compound were more pronounced than those of Xymedon.

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.

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.

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.

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.

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.

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.

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.

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.