Work in progress: radioprotection of human breast cancer cells by elevation of intracellular cyclic AMP

MCF-7 human breast cancer cells that were treated for one hour prior to X irradiation with the cyclic AMP-inducing agent 1-methyl-3-isobutylxanthine displayed a slight but significant increase in surviving fraction over untreated controls at each radiation dose level. This was accompanied by a two-fold increase in the level of intracellular cyclic AMP.     

碳糊电极溶出伏安法测定奋乃静等抗精神病药物

本文报道一种测定吩噻嗪类治疗精神病药物奋乃静、氟奋乃静、氯丙嗪和三氟拉嗪的灵敏电化学分析方法。该类药物在碳糊电极上预富集后,进行溶出伏安测定,溶出电流与浓度在一定范围内具有线性关系。最低检测限可达5ng/ml。用本方法可以不经分离,直接测定药片和人体液中上述药物的含量。作者提出了一种新型挤压式碳糊电极,对上述药物在该电极上的富集机理和测试条件进行了系统研究。认为药物的富集作用是由吸附和萃取引起的,并用计时库仑法定量地估价了这两部分在富集中所起的作用。     

Targeting zymogen activation to control the matriptase-prostasin proteolytic cascade

Membrane-associated serine protease matriptase has been implicated in human diseases and might be a drug target. In the present study, a novel class of matriptase inhibitors targeting zymogen activation is developed by a combination of the screening of compound library using a cell-based matriptase activation assay and a computer-aided search of commercially available analogues of a selected compound. Four structurally related compounds are identified that can inhibit matriptase activation with IC(50) at low micromolar concentration in both intact-cell and cell-free systems, suggesting that these inhibitors target the matriptase autoactivation machinery rather than the intracellular signaling pathways. These activation inhibitors can also inhibit prostasin activation, a downstream event that occurs in lockstep with matriptase activation. In contrast, the matriptase catalytic inhibitor CVS-3983 at a concentration 300-fold higher than its K(i) fails to inhibit activation of either protease. Our results suggest that inhibiting matriptase activation is an efficient way to control matriptase function.