PATHOGENESIS AND TREATMENT OF EXPERIMENTAL PERITONITIS

描述：(改编自申请人的摘要)细菌 易位(Bt)的定义是微生物从 肠腔到宿主体内的任何腔外部位。一些Bt很可能是 很正常。然而，各种重音夸大了BT，并导致了 系统性感染的发病机制。初步数据显示，没有 肠细胞的产生可能在肠炎的发病机制中起着调节作用 夸大了英国电信。在某些病理条件下，可能会产生过量的NO 诱导细胞损伤，导致肠上皮细胞凋亡 障碍失效和BT增加。这项研究的目标是确定 体内和体外NO调节Bt的机制。这项研究已经 三个具体目标：i)研究一氧化氮合酶-2在脑内的调节 肠道受多种因素影响，包括细胞因子、肠腔内容物和 上皮内淋巴细胞；ii)利用NOS-2基因敲除小鼠 以及一氧化氮合酶-2基因转移实验，一氧化氮调节的机制 细菌的跨粘膜传代；iii)确定不同种类的 Bt上的活性氮物种(RNI)。

DESCRIPTION: (Adapted from the applicant's abstract) Bacterial translocation (BT) is defined as the transfer of microbes from the intestinal lumen to any extra-luminal site in the host. Some BT is probably normal. However, a variety of stresses exaggerate BT and contribute to the pathogenesis of systemic infections. Preliminary data suggest that NO production by enterocytes may play a regulatory role in the pathogenesis of exaggerated BT. In certain pathologic conditions, overproduction of NO may induce cellular injury and lead to enterocyte apoptosis resulting in gut barrier failure and increased BT. The goal of the study is to determine the mechanisms by which NO regulates BT in vivo and in vitro. The study has three specific aims: I) to study the regulation of NOS-2 within the intestine by various factors, including cytokines, luminal contents, and intra-epithelial lymphocytes; II) to determine, using NOS-2 knockout mice and NOS-2 gene-transfer experiments, the mechanisms by which NO regulates transmucosal passage of bacteria; III) to determine the effect of various reactive nitrogen species (RNI) on BT.