No abstract

The changes in short circuit current (electrogenic a-secretion) of rat colon brought about by xanthine/xanthine oxidase in the Ussing chamber were inhibited by catalase and diethyldithiocarbamate, but not by superoxide dismutase. These results, the reproduction of the response with glucose/glucose oxidase and with exogenous H202, and the lack of effect of preincubation with deferoxamine or thiourea implicate H202, and not 02 or OH, as the important reactive oxygen metabolite altering intestinal electrolyte transport. 1 mM H202 stimulated colonic PGE2 and PGI2 production 8-and 15-fold, respectively, inhibited neutral NaCl absorption, and stimulated biphasic electrogenic a secretion with little effect on enterocyte lactic dehydrogenase release, epithelial conductance, or histology. a-secretion was reduced by cyclooxygenase inhibition. Also, the Cl-secretion, but not the increase in prostaglandin production, was reduced by enteric nervous system blockade with tetrodotoxin, hexamethonium, or atropine. Thus, H202 appears to alter electrolyte transport by releasing prostaglandins that activate the enteric nervous system. The change in short circuit current in response to Iloprost, but not PGE2, was blocked by tetrodotoxin. Therefore, PGI2 may be the mediator of the H202 response. H202 produced in nontoxic concentrations in the inflamed gut could have significant physiologic effects on intestinal water and electrolyte transport. (J.

The adverse gastrointestinal effects of octreotide, a synthetic analog of somatostatin, have not been fully elucidated. Low-dose octreotide frequently causes adverse gastrointestinal symptoms in normal individuals. We investigated the adverse gastrointestinal effects of high-dose octreotide, which is required for the normalization of growth hormone hypersecretion in some patients with acromegaly. Patients with acromegaly (N = 8) were treated with octreotide, 450 micrograms/day, then 1500 micrograms/day for two months at each dosage. Carbohydrate absorption was assessed using the D-xylose test, and fat absorption using fecal fat excretion and serum carotene concentrations, at baseline, at each dosage of octreotide, and after one month of washout. Ultrasonography was used to monitor for cholelithiasis. Growth hormone and insulin-like growth factor-I concentrations were significantly suppressed at both dosages. Adverse gastrointestinal symptoms were mild and transient. D-Xylose absorption remained normal at each dosage and after one month of washout. Fecal fat excretion increased from 7 +/- 2 to 12 +/- 2 g/24 hr (P < 0.05) after the higher dosage and resumed baseline levels after the washout. Mean fasting serum carotene levels remained normal, and carotene loading test (15,000 units three times a day for three days) was unreliable in identifying patients with high fecal fat. No new cholelithiasis was detected by ultrasonography. One of two patients with preexisting cholelithiasis developed biliary colic several days after the treatment period. Although steatorrhea was common, small intestinal absorptive capacity was otherwise unchanged by four months of high-dose octreotide treatment, which significantly suppressed growth hormone secretion in acromegalic patients.