100 research outputs found
Inhibiting Inducible Nitric Oxide Synthase in Enteric Glia Restores Electrogenic Ion Transport in Mice With Colitis
BACKGROUND & AIMS: Disturbances in the control of ion transport lead to epithelial barrier dysfunction in patients with colitis. Enteric glia regulate intestinal barrier function and colonic ion transport. However, it is not clear whether enteric glia are involved in the epithelial hypo-responsiveness. We investigated enteric glial regulation of ion transport in mice with trinitrobenzene sulphonic acid- or dextran sodium sulfate-induced colitis and in Il10(−/−) mice. METHODS: Electrically-evoked ion transport was measured in full-thickness segments of colon from CD1 and Il10(−/−) mice with or without colitis in Ussing chambers. Nitric oxide (NO) production was assessed using amperometry. Bacterial translocation was investigated in the liver, spleen and blood of mice. RESULTS: Electrical stimulation of the colon evoked a tetrodotoxin-sensitive chloride secretion. In mice with colitis, ion transport almost completely disappeared. Inhibiting inducible NO synthase (NOS2), but not neuronal NOS (NOS1), partially restored the evoked secretory response. Blocking glial function with fluoroacetate, which is not a NOS2 inhibitor, also partially restored ion transport. Combined NOS2 inhibition and fluoroacetate administration fully restored secretion. Epithelial responsiveness to vasoactive intestinal peptide was increased after enteric glial function was blocked in mice with colitis. In colons of mice without colitis, NO was produced in the myenteric plexus almost completely via NOS1. NO production was increased in mice with colitis, compared to mice without colitis; a substantial proportion of NOS2 was blocked by fluoroacetate administration. Inhibition of enteric glial function in vivo reduced the severity of trinitrobenzene sulphonic acid -induced colitis and associated bacterial translocation. CONCLUSIONS: Increased production of NOS2 in enteric glia contributes to the dysregulation of intestinal ion transport in mice with colitis. Blocking enteric glial function in these mice restores epithelial barrier function and reduces bacterial translocation
An epitaph to Section 28? Telling tales out of school about changes and challenges to discourses of sexuality
This is a postprint of an article whose final and definitive form has been published in the International Journal of Qualitative Studies in Education,© 2007 Copyright Taylor & Francis; International Journal of Qualitative Studies in Education, is available online at http://www.informaworld.comThis article seeks to develop an understanding of the professional and personal lives of LGBT teachers in relation to the discriminatory statute Section 28, which prohibited 'promotion' of 'the acceptability of homosexuality as a pretended family relationship' by local education authorities in the UK (except Northern Ireland). Interviews with a small sample of serving teachers are analysed using a feminist poststructuralist methodology to discover whether the removal of this legislation marks a shift in theorization, policy or practice. Findings are arranged to focus on the workings of official policy, on informal or unofficial classroom and staffroom practices, and on relations with a local community. Analysis and discussion reveal a complex matrix of constituents (space, relationships and other variables) only some of which respond to the (perhaps) superficial stimulus of legislative change. Such change goes only a small way to challenge a deeply embedded discourse of inequality, which may respond only to a more profound epistemological transformation
Epithelial effects of proteinase-activated receptors in the gastrointestinal tract
The intestinal epithelium plays a crucial role in providing a barrier
between the external environment and the internal milieu of the body. A
compromised mucosal barrier is characteristic of mucosal inflammation
and is a key determinant of the development of intestinal diseases such
as Crohn's disease and ulcerative colitis. The intestinal epithelium is
regularly exposed to serine proteinases and this exposure is enhanced
in numerous disease states. Thus, it is important to understand how
proteinase-activated receptors (PARs), which are activated by serine
proteinases, can affect intestinal epithelial function. This review
surveys the data which demonstrate the wide distribution of PARs,
particularly PAR-1 and PAR-2, in the gastrointestinal tract and
accessory organs, focusing on the epithelium and those cells which
communicate with the epithelium to affect its function. PARs have a
role in regulating secretion by epithelia of the salivary glands,
stomach, pancreas and intestine. In addition, PARs located on
subepithelial nerves, fibroblasts and mast cells have important
implications for epithelial function. Recent data outline the
importance of the cellular site of PAR expression, as PARs expressed on
epithelia may have effects that are countered by PARs expressed on
other cell types. Finally, PARs and their ability to promote epithelial
cell proliferation are discussed in terms of colon cancer
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