预断溃疡性结肠炎自然史的可能性

在提高炎症性肠病(1BD)疗效的同时,因治疗产生的毒性也可能增加,因此筛选出高危患者尤为重要.我们首先需要确定与溃疡性结肠炎(UC)自然史最为相关的临床终点事件,然后明确能预测严重后果的危险因素.     

Hypercholesterolemia-induced oxidative stress in heart and its prevention by vitamin E

Oxygen-free radicals have been implicated in hypercholesteolemic atherosclerosis. It is possible that hypercholesterolemia produces oxidative stress in myocardium. We therefore investigated the effects of a high cholesterol diet in the absence or presence of vitamin E on serum cholesterol and lipid peroxidation product malondialdehyde (MDA), chemiluminescence (M-CL), a measure of antioxidant reserve, and activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-P_x)] in cardiac muscles of rabbits. Rabbits were divided into four groups: Group I, regular rabbit chow diet; Group II, same as Group I + vitamin E; Group III, high cholesterol diet; Group IV, high cholesterol + vitamin E. The heart was removed under anesthesia at the end of 4 months on their respective diets for various biochemical measurements. Serum cholesterol in Groups III and IV increased to a similar extent. There was an increase in the levels of MDA, M-CL, GSH-P_x activity and a decrease in SOD activity in hypercholesterolemic rabbits in the absence of vitamin E. Vitamin E prevented the hypercholesterolemia-induced changes in cardiac MDA, M-CL, and GSH-P_x. These results suggest that hypercholesterolemia produces oxidative stress in the myocardium which may be due to a decrease in the antioxidant reserve, and that vitamin E is effective in preventing hypercholesterolemia-induced oxidative stress on the myocardium.     

Molecular docking study,synthesis and biological evaluation of Schiff bases as Hsp90 inhibitors

Heat shock protein 90 (Hsp90) is an emerging attractive target for the discovery of novel cancer therapeutic agents. Docking methods are powerful in silico tools for lead generation and optimization. In our mission to rationally develop novel effective small molecules against Hsp90, we predicted the potency of our designed compounds by Sybyl surflex Geom X docking method. The results of the above studies revealed that Schiff bases derived from 2,4-dihydroxy benzaldehyde/5-chloro-2,4-dihydroxy benzaldehyde demonstrated effective binding with the protein. Subsequently, a few of them were synthesized (1–10) and characterized by IR, ¹HNMR and mass spectral analysis. The synthesized molecules were evaluated for their potential to suppress Hsp90 ATPase activity by Malachite green assay. The anticancer studies were performed by 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The software generated results was in satisfactory agreement with the evaluated biological activity.     

Effect of carrageenan on the resistance of congenitally athymic nude and normal BALB/c mice to infective larvae ofBrugia malayi

Resistance of BALB/c mice to infective thirdstage larvae (L3) of the human filarial parasiteBrugia malayi is thymus-dependent, although the actual, effector mechanisms that mediate larval killing are unknown. The present study examined the effect of carrageenan (CGN) on the mechanisms of resistance toB. malayi infection in heterozygous (nu/+) and nude (nu/nu) mice. Mice were treated with CGN at a single dose of 20 or 200 mg/kg and were inoculated intraperitoneally 1 day later with 100 L3. The results showed a dose-dependent increase in the numbers of L4 and L5 that were recovered from nu/+ and nu/nu mice. CGN treatment also enhanced the recovery of mature adult worms from nu/nu mice and appeared to abolish partially the dichotomy of resistance between the usually more susceptible male and the more resistant female nu/nu mouse. Microfilariae were found in the peripheral blood and the peritoneal cavity of CGN-treated male and female nu/nu mice and in the peritoneal cavity of male but not female nu/+ mice. Fewer larval granulomas were recovered from the peritoneal cavity of treated mice. CGN-treated, parasitized nu/+ and nu/nu mice showed high titers of IgM and IgG antibodies. An experimental compound, CGP 20376, showed 100% larvicidal activity following the administration of a single dose of 20mg/kg to CGN-treated mice. From this study, we conclude that macrophages alone or in conjunction with other cells are actively involved in the resistance of mice toB. malayi L3.Supported by research grant AI 20052 from the, NIAID (NIH). The senior author (U.R.R.) was supported by the filariasis component of the UNDP/World Bank/WHO program (project 870382). The results were presented in part at the 39th annual meeting of the American Society of Tropical Medicine and Hygiene, New Orleans, November 4–8, 1990