Oxygen derived radicals contribute to tissue injury in inflammatory bowel disease. We measured the content of superoxide dismutase and metallothionein (two endogenous copper and zinc containing proteins involved in radical scavenging) in intestinal resection specimens from 29 patients with Crohn's disease and 12 patients with ulcerative colitis and compared the concentrations with those obtained in the normal mucosa of a control group of 18 patients with colorectal cancer. The superoxide dismutase content was similar in control mucosa and non-inflamed mucosa from patients with inflammatory bowel disease (mean (SEM) 2.13 (0.10) and 2.24 (0.10) mg/g protein, respectively) but was decreased in inflamed mucosa (1.87 (0.08) mg/g protein, p

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Oxygen-derived free radicals may contribute to intestinal tissue damage in inflammatory bowel disease. The concentrations of metallothionein and superoxide dismutase, two copper and zinc containing proteins involved in the scavenging of free radicals; were previously found to be decreased in the intestinal mucosa of patients with this disorder. The plasma zinc concentration is often decreased also in these patients. Since zinc is reported to be an efficient inducer of metallothionein synthesis, and probably of superoxide dismutase, we evaluated the effect of oral zinc supplementation on metallothionein and superoxide dismutase levels in patients with inflammatory bowel disease. Fourteen patients with inactive to moderately active inflammatory bowel disease received oral zinc supplementation (300 mg zinc aspartate, equal to 60 mg elemental zinc per day) for 4 weeks in a placebo-controlled double-blind cross-over trial. The plasma zinc concentration of these patients was low at the start of the study (12.2 +/- 1.7 mumol/L, P < 0.05), when compared to that of 22 healthy controls (13.6 +/- 2.3 mumol/L), but increased (P < 0.05) towards the levels of controls during the supplementation period (13.3 +/- 2.5 mumol/L). The concentrations of metallothionein and superoxide dismutase in plasma and in erythrocytes did not change in relation to the supplementation. The metallothionein concentration in both inflamed and non-inflamed intestinal mucosa was slightly higher after zinc supplementation but the superoxide dismutase concentration in the tissue was not altered. The histological inflammation score of intestinal biopsies, plasma albumin levels, and the disease activity index of the patients did not change during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

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Antipyrine (AP), hexobarbital (HB) and theophylline (TH) were administered simultaneously ('cocktail' design) to 24 patients with various types of liver disease. Clearance (Cl) of AP, HB and TH and formation clearance of the AP-metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA) and 4-hydroxyantipyrine (OHA) were determined and correlation coefficients and orthogonal least-squares regression lines calculated between the clearance and formation clearance parameters. The results were compared with those obtained in a study in which the same 'cocktail' was administered to 26 healthy control subjects. In the patients ClAP, ClHB and ClTH were 23.0 +/- 14.3 ml min-1, 206 +/- 128 ml min-1 and 39.9 +/- 26.1 ml min-1 respectively. All values were considerably lower than those found in the control subjects. With regard to AP metabolism preferential impairment of NORA formation was observed. Relatively high correlation coefficients were found between ClAP, ClHB and ClTH, which suggests, like the results of orthogonal regression analysis, a strong correlation between total metabolism of these probe drugs. Therefore it is likely that impairment in oxidation in patients with liver disease not only leads to reduction in clearance but also to reduced substrate selectivity of cytochrome P-450 isozymes.