Comparative Analysis of the Pharmacological Activity of Bis(3,5-di-Tert-Butyl-4-Hydroxyphenylthiolate)Dimethylol in Different Modes of Administration on a Mouse Model of Melanoma B16 Tumor Growth.

We performed a comparative analysis of the pharmacological activity of the hybrid organotin compound bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate)dimethylol (Me-3) administered in different modes to mice with transplanted melanoma B16 to identify the most effective dosage regimen. Three modes of administration were used: preventive (before transplantation of tumor cells), classical according to Z. P. Sof'ina (48 h after transplantation of tumor cells), and delayed (7 days after transplantation of tumor cells, after formation of nodules of the primary tumor node). Compound Me-3 was administered at a total dose of 375 mg/kg intraperitoneally once a day for 5 days. The classical mode of administration was identified as the most effective, which indicates the preventive antimetastatic activity of Me-3 on the model of the transplanted mouse tumor melanoma B16.

Effect of Hybrid Organotin Compound on Activity of LPO and Antioxidant Protection of the Liver Tissues in Animals with Melanoma B16.

The central element of the "metastatic organotropism" is a shift of the pro/antioxidant balance in cells and activation of oxidative stress and protective antioxidant systems. We studied the effects of bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate)dimethylol (Me-3) in the maximum effective and toxic total doses on the level of markers of oxidative stress and antioxidant protection in the liver of mice with melanoma B16 before the appearance of macroscopic metastases. In 48 h after tumor inoculation, Me-3 was administered intraperitoneally once a day for 5 days in total doses of 375 and 500 mg/kg according to the classical method. Administration of the hybrid organotin compound Me-3 produced different effects on the pro/antioxidant state of the microenvironment of liver tissue as the target of melanoma B16 metastasis. The results suggest that inversion of the anti/prooxidant profile of Me-3 is determined by its dose.

Laboratory control of the osteoresorptive effects of glucorcorticoids in patients with purpose colitis.

The aim of the work was to develop an informative method for laboratory monitoring of osteoresorbent action during systemic administration of glucocorticoids in patients with ulcerative colitis. The study included 54 patients with ulcerative colitis aged 18 to 44 years: 35 (64,8%) men and 19 (35,2%) women. In patients of the clinical group before and after the first, second, third courses of glucocorticosteroids, as well as during the formation of steroid dependence, the concentration of the osteoresorption marker cathepsin K was determined simultaneously in the blood serum and gingival fluid by enzyme immunoassay. The concentration of the osteomarker was compared with the parameters of the densitometric density of the lumbar vertebrae L1-L4 during X-ray examination. It was found that with the systemic use of glucocorticoids in patients with ulcerative colitis, the concentration of cathepsin K in the gingival fluid increased earlier than in the blood serum. It was found that with an increase in the concentration of cathepsin K in the gingival fluid of more than 2,6 pmol/l in conditions of systemic administration of glucocorticosteroids, the risk of osteoporosis increased with a diagnostic sensitivity of 81,8% and a specificity of 74,4% (p=0,0001).The diagnostic accuracy was 78,1%. With an increase in the concentration of cathepsin K in the gingival fluid above the differential separation level (2,6 pmol/l), the risk of developing osteoporosis increased 3,2 times (p= 0,0001). The study developed a methodological and informational algorithm has been developed for the non-invasive control of steroidal osteoporosis in patients with ulcerative colitis with systemic use of glucocorticoids by assessing the concentration of cathepsin K in the gingival fluid.