ABSTRACT
New antithrombotic drug GRS, a soluble guanylate cyclase stimulator, after repeated administration in a dose of 10 mg/kg alleviates the symptoms of endothelial dysfunction in rats with myocardial infarction; it restores antiplatelet activity of the blood vessel wall and vasodilatory function of the endothelium without producing significant effect on endothelium-independent vasodilation. GRS also has direct antiaggregant and antihypertensive effects in therapeutic doses. The obtained data suggest that GRS can be therapeutically useful in patients with cardiovascular diseases accompanied by endothelial dysfunction.
Subject(s)
Guanylate Cyclase , Myocardial Infarction , Animals , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/therapeutic use , Humans , Myocardial Infarction/drug therapy , Nitric Oxide , Rats , Soluble Guanylyl Cyclase , Vasodilator Agents/pharmacologyABSTRACT
The anti-inflammatory effect of the ester derivative of indomethacin (IML) in doses of 6.25, 12.5, and 25 mg/kg was studied in rats with modeled rheumatoid arthritis (adjuvant arthritis) and compared to the effects of the reference drug indomethacin in a dose of 1 mg/kg. IML in doses of 12.5 and 25 mg/kg reduced joint inflammation and promoted recovery of the microstructure of the synovial membrane and articular cartilage better than indomethacin. IML produced no ulcerogenic effect, while indomethacin concentration in the stomach wall after administration of IML was 1.8-3.4 times lower than after administration of the reference drug (p<0.05).
Subject(s)
Arthritis, Experimental/drug therapy , Indomethacin/pharmacology , Indomethacin/therapeutic use , Inflammation/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Experimental/metabolism , Inflammation/metabolism , Male , Rats , Rats, Wistar , Synovial Membrane/drug effects , Synovial Membrane/metabolismABSTRACT
The total count, spontaneous proliferation and proliferative response of thymic and spleen T-cells in mixed lymphocyte culture and Con A-induced suppressor activity do not reveal significant disorders in 10-14-month A/Sn and C3H/He mice with spontaneous mammary tumors (weight under 2-3 g). However, these indices are quite different in varying age (2, 6, 12 month) A/Sn mice and C57Bl/6 mice with low rates of spontaneous tumors. The analysis of thymus-dependent immunity changes observed with age shows that relatively intensive migration of nonmature thymocytes, T-suppressor precursors is noted in mice with high cancer incidence. This phenomenon is considered to be one of major mechanisms regulating immune response in spontaneous-carcinogenesis.