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Microscopic colitis (MC) is a common and previously under-recognized cause of chronic diarrhea. In 1 study, MC was found in 10% of all patients with nonbloody diarrhea referred for colonoscopy [...], Microscopic colitis (MC) is an inflammatory condition of the colon distinct from Crohn disease or ulcerative colitis that can cause chronic diarrhea as well as cramping and bloating. Although it was first described 30 years ago, awareness of this entity as a cause of diarrhea has only become more widespread recently. Up to 20% of adults with chronic diarrhea who have an endoscopically normal colonoscopy may have MC. Endoscopic and radiological examinations are usually normal, but histology reveals increased lymphocytes in the colonic mucosa, which typically cause watery nonbloody diarrhea. Treatment is initially supportive but can include corticosteroids and immunomodulatory therapy for resistant cases. Since surgeons perform a large number of colonoscopies and sigmoidoscopies to assess diarrhea, it is important to be aware of this disease and to look for it with mucosal biopsy in appropriate patients. La colite microscopique (CM) est une inflammation du colon differente de la maladie de Crohn ou de la colite ulcereuse, et qui peut causer une diarrhee chronique, des crampes et du ballonnement. Meme si on l'a decrite pour la premiere fois il y a 30 ans, la connaissance de cette entite comme cause de diarrhee ne s'est generalisee que recemment. Jusqu'a 20% des adultes presentant une diarrhee chronique et dont la coloscopie est normale sur le plan endoscopique peuvent etre atteints de CM. L'endoscopie et la radiologie donnent habituellement des resultats normaux, mais l'histologie revele une elevation des lymphocytes dans la muqueuse du colon, ce qui cause typiquement une diarrhee aqueuse non sanglante. Le traitement initial consiste a donner du soutien, mais peut inclure l'administration de corticosteroides et d'immunomodulateurs dans les cas resistants. Comme les chirurgiens pratiquent de nombreuses coloscopies et sigmoidoscopies pour evaluer la diarrhee, il importe d'etre conscient de cette maladie et de la rechercher par biopsie de la muqueuse chez les patients qui semblent presenter ce profil.

Glucagon-like peptide-1 (GLP-1), an incretin, which is used to treat diabetes mellitus in humans, inhibited vagal activity and activated nitrergic pathways. In rats, GLP-1 also increased sympathetic activity, heart rate, and blood pressure (BP). However, the effects of GLP-1 on sympathetic activity in humans are unknown. Our aims were to assess the effects of a GLP-1 agonist with or without [[alpha].sub.2]-adrenergic or -nitrergic blockade on autonomic nervous functions in humans. In this double-blind study, 48 healthy volunteers were randomized to GLP-1-(7-36) amide, the nitric oxide synthase (NOS) inhibitor [N.sup.G]-monomethyl-L-arginine acetate (L-NMMA), the [[alpha].sub.2]-adrenergic antagonist yohimbine, or placebo (i.e., saline), alone or in combination. Hemodynamic parameters, plasma catecholamines, and cardiac sympathetic and parasympathetic modulation were measured by spectral analysis of heart rate. Thereafter, the effects of GLP-1-(7-36) amide on muscle sympathetic nerve activity (MSNA) were assessed by microneurography in seven subjects. GLP-1 increased (P = 0.02) MSNA but did not affect cardiac sympathetic or parasympathetic indices, as assessed by spectral analysis. Yohimbine increased plasma catecholamines and the low-frequency (LF) component of heart rate power spectrum, suggesting increased cardiac sympathetic activity. L-NMMA increased the BP and reduced the heart rate but did not affect the balance between sympathetic and parasympathetic activity. GLP-1 increases skeletal muscle sympathetic nerve activity hut does not appear to affect cardiac sympathetic or parasympathetic activity in humans. nitric oxide; adrenergic; catecholamines; spectral analysis; heart rate

The incretin glucagon-like peptide-1 (GLP-1), which is used to treat diabetes mellitus, delays gastric emptying by inhibiting vagal activity. GLP-1 also increases fasting and postprandial gastric volume in humans. On the basis of animal studies, we hypothesized that nitric oxide mediates the effects of GLP-1 on gastric volumes. To assess the effects of nitrergic blockade on GLP-l-induced gastric accommodation in humans, in this double-blind study, 31 healthy volunteers were randomized to placebo (i.e., saline), GLP-1, or the nitric oxide synthase inhibitor [N.sup.G]-monomethyl-L-arginine acetate (L-NMMA; 4 mg x [kg.sup.-1] x [h.sup.-1]) alone or with GLP-1. Thereafter, 16 additional subjects were randomized to GLP-1 alone or together with a higher dose of L-NMMA (10 mg/kg bolus plus 8 mg x [kg.sup.-1] x [h.sup.-1] infusion). Gastric volumes (fasting pre- and postdrug, postprandial postdrug) were measured by [sup.99m]Tc-single-photon-emission computed tomography imaging. GLP-1 increased (P = 0.04) fasting gastric volume by 83 [+ or -] 16 ml (vs. 17 [+ or -] 11 ml for placebo) and augmented (P [less than or equal to] 0.01) postprandial accommodation by 688 [+ or -] 165 ml (vs. 542 [+ or -] 29 ml for placebo). L-NMMA (low dose) alone did not affect fasting or postprandial gastric volume. L-NMMA (low dose) did not attenuate the effect of GLP-1 on gastric volumes. In contrast, L-NMMA (high dose) did not affect fasting volume but blunted GLP-1-mediated postprandial accommodation (postprandial change = 494 [+ or -] 37 ml, P [less than or equal to] 0.01 vs. GLP-1 alone). These data are consistent with the hypothesis that nitric oxide partly mediates the effects of GLP-1 on postprandial but not fasting gastric volumes in humans. accommodation; stomach; postprandial; diabetes; vagus doi:10.1152/ajpgi.00403.2006.

Mediators involved in the generation of symptoms in patients with irritable bowel syndrome (IBS) are poorly understood. Here we show that colonic biopsy samples from IBS patients release increased levels [...]