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Infiltration of specific immunocytes and stimulation of abnormal gastrointestinal motor activity during ileal inflammation induced by mucosal exposure to ethanol and acetic acid were investigated in 17 dogs. Ileal inflammation significantly increased the frequency of giant migrating contractions (GMCs) and decreased the frequency of migrating motor complexes (MMCs). The frequency of retrograde giant contractions (RGCs) increased only on the day of ethanol and acetic acid treatment. Diarrhea, urgency of defecation, and apparent abdominal discomfort were related to the increased frequency of GMCs. Ileal inflammation also prolonged the duration of postprandial MMC disruption. Histological and immunohistochemical findings indicated transmural inflammation with marked increase in polymorphonuclear cells in the lamina propria and muscularis externa layers. Myeloperoxidase activity increased severalfold in both layers. Cells containing interleukin-2 receptor (IL-2R) increased in the lamina propria. Other immunocytes, such as B and T lymphocytes, dendritic cells, and human leukocyte antigen DR-1 (HLADR)-positive cells, did not exhibit a significant increase in the inflamed ileum compared with the normal proximal jejunum. We conclude that stimulation of GMCs may be the major motility marker of intestinal inflammation.

Background-The possible role of nitric oxide in the regulation of the sphincter of Oddi is not known in species with a resistor-like sphincter of Oddi such as humans and pigs. Methods-Sphincter of Oddi perfusion manometry and simultaneous electromyography (EMG) were recorded transduodenally in eight anaesthetised pigs. Acetylcholine (4 µg/kg) was given intraarterially, with or without sodium nitroprusside (10-100 µg/kg), an exogenous nitric oxide donor. For in vitro studies the sphincter was removed from the eight pigs and from six patients undergoing pancreaticoduodenectomy, cut into rings, and the amplitude of contraction was measured in an ex vivo bath. Each ring was stimulated with acetylcholine (100 µM) and KCl (125 mM). The stimulation was repeated after incubation with L-NAME (a stereospecific competitive inhibitor of nitric oxide synthase), with L-NAME plus L-arginine (a substrate for nitric oxide synthase), and with sodium nitroprusside. The sphincter rings were then submersed in liquid nitrogen and stored. Immunohistochemical analysis was used to localise nitric oxide synthase in the pig and human sphincter specimens. Results-In vivo EMG revealed 2-3 phasic bursts per minute with the basal pressure variation 6-40 mm Hg. Acetylcholine induced a large electrical burst and the pressure increased by (mean (SE)) 20 (10) mm Hg (p <0.01) for 17 (4) seconds. After sodium nitroprusside (10 µg/kg) acetylcholine did not induce pressure changes and electrical activity was almost abolished. In vitro, L-NAME increased the KCl induced sphincter contraction in both pig and human specimens (p<0.01). In human, but not in pig, specimens L-NAME increased the amplitude of acetylcholine induced contraction (p<0.01). L-Arginine partly reversed the eVect of L-NAME in both pig and human specimens. Sodium nitroprusside decreased the acetylcholine and KCl induced contractions in both pig and human specimens. Immunohistochemical studies localised nitric oxide synthase to rich plexi of nerve fibres in the mucosa and the muscle in both pig and human sphincter of Oddi. Conclusions-The sphincter of Oddi in both pigs and humans has endogenous nitric oxide synthase activity and immunoreactivity. Inhibition of endogenous nitric oxide production enhances contractility while exogenous nitric oxide decreases sphincter contractility and electrical activity. (Gut 1997; 41: 375-380) Keywords: NO; nitric oxide synthase; nitroprusside; sphincter of Oddi; pig; human The sphincter of Oddi (SO) regulates bile flow into the duodenum by behaving either as a pump (category I) or as a passive resistor (category II), depending upon the species of animal.1 2 The physiological control of the SO is complex and includes both neural and humoral factors. In recent years much attention has been focused on the role of nitric oxide (NO), a potent smooth muscle relaxant produced by enteric nerves, in the regulation of gastrointestinal smooth muscle function. NO is known to cause relaxation of the SO in category I species (with a pump-like sphincter) s...