亚胺培南-西司他丁联合去甲万古霉素治疗获得性下呼吸道感染的效果

目的:探讨亚胺培南与西司他丁联合去甲万古霉素对重症获得性下呼吸道感染患者治疗效果。方法:回顾性分析获得性下呼吸道感染患者70例临床资料,其中36例为观察组,采用亚胺培南与西司他丁联合去甲万古霉素治疗;其余34例为对照组,采用哌拉西林与他唑巴坦联合左氧氟沙星沙星治疗。比较两组患者治疗7天后的效果、症状缓解时间、治愈时间、住院花费及不良反应发生率。结果:观察组有效率高于对照组,差异有统计学意义(P0.05);观察组症状缓解时间及治愈时间较对照组短,但住院花费高于对照组,差异有统计学意义(P0.05);观察组不良反应发生率高于对照组,差异有统计学意义(P0.05)。结论:亚胺培南与西司他丁联合去甲万古霉素对获得性下呼吸道感染患者治疗显著,但不良反应较多,需临床加以重视。     

Binding mode analysis between membrane dipeptidase and its substrates

Membrane dipeptidase (MDP) is a membrane-bound glycoprotein involved in the hydrolysis of dipeptides, showing specific activity for dipeptides. Recent study showed that membrane dipeptidase was the receptor for a lung-targeting peptide identified by in vivo phage display and the crystal structure of the cilastatin-liganded human renal dipeptidase was determined. We performed a pharmacophore-based virtual screening and molecular docking in order to characterize MDP binding interactions with its substrates. A ligand-based pharmacophore model represented only a slight enrichment because of a lacked variety and centralization of ligand features. Molecular docking study was used to incorporate ligand conformational changes in the binding sites and the performance was much better than pharmacophore model; only 10% of compound library needed to be screened in order to detect all included active compounds. In addition, we found that one of the crystallographically observed water molecules plays an important role in the binding modes between MDP and its substrate.