Kinetics of butyrate metabolism in the normal colon and in ulcerative colitis: the effects of substrate concentration and carnitine on the ß-oxidation pathway.

BACKGROUND: Butyrate, a colonic metabolite of carbohydrates, is considered as the major energy source for the colonic mucosa. An impaired butyrate metabolism has been reported in ulcerative colitis (UC), however, the cause still remains unknown. AIM: In the present study, we investigated whether higher butyrate concentrations could normalise the oxidation rate in UC. Furthermore, it was investigated whether carnitine could enhance the butyrate oxidation. METHODS: Mucosal biopsies from a total of 26 UC patients and 25 controls were incubated with (14)C-labelled Na-butyrate and the produced (14)CO(2) was measured. First, the rate of oxidative metabolism was compared at three different concentrations of Na-butyrate (0.05 mm, 1 mm and 10 mm). Then, incubations of biopsies were performed with carnitine alone or combined with ATP. RESULTS: Overall, butyrate oxidation in UC was significantly lower than that in controls. The maximum rate of butyrate oxidation was achieved in UC and control subjects from 1 mm onwards. Increasing the butyrate concentration to a level to be present in the colonic lumen, i.e. 10 mm, did not increase the rate of butyrate oxidation in UC to the rate observed in controls. Addition of carnitine alone or combined with ATP caused no effects. CONCLUSIONS: Saturation of butyrate kinetics was achieved from 1 mm in UC and control subjects. The rate of butyrate metabolism was significantly impaired in active ulcerative colitis. The addition of compounds interfering with the ß-oxidation pathway had no effect on the butyrate metabolism in UC.

In vivo influence of nicotine on human basal and NSAID-induced gut barrier function.

BACKGROUND: Smoking reduces the non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal permeability increase in healthy people. It also affects inflammatory bowel disease that is associated with a disturbed gut barrier function. To assess the role of nicotine on barrier function, its influence on basal and NSAID-induced intestinal permeability was studied in healthy volunteers. METHODS: Thirty-one healthy non-smoker subjects performed permeability tests with 51Cr-EDTA and sugar markers (sucrose, lactulose, mannitol, sucralose) before and during 2 weeks of nicotine patch application, and with and without indomethacin intake, respectively. Since smoking has been described as affecting motility, transit measurements were also done with the sodium[13C]-octanoate and lactose-[13C]-ureide breath tests before and during nicotine exposure. Correlations between permeability markers were checked and the influence of gastrointestinal transit was assessed. RESULTS: Nicotine did not affect barrier function in vivo, nor gastric emptying, small-bowel transit time or orocaecal transit. 51Cr-EDTA and lactulose correlated in basal 0-6 h permeability testing (r = 0.529, P < 0.0001), as did 6-24 h excretion of 51Cr-EDTA and sucralose (r = 0.474, P < 0.001); 97% and 90% of the subjects had a permeability increase after indomethacin intake for 0-6 h and 6-24 h excretion of Cr-EDTA, respectively. This population proportion is 63% for lactulose/mannitol and 83% for sucralose. CONCLUSIONS: Short-term exposure to nicotine does not alter normal basal or NSAID-induced gut barrier function or transit. 51Cr-EDTA and the respective sugar markers correlate well in in vivo permeability testing in healthy humans. The radioactive test detects more NSAID-induced permeability increase than does the lactulose/mannitol ratio permeability test.

The effects of smoking and indomethacin on small intestinal permeability.

BACKGROUND: Smoking modulates inflammatory bowel disease, protecting from ulcerative colitis on the one hand and worsening the course of Crohn's disease on the other. This influence might occur through changes in intestinal permeability, because permeability is increased in most patients with Crohn's disease. AIM: To study the influence of smoking on small intestinal permeability and its increase induced by indomethacin. METHODS: 50 smokers and 50 nonsmokers underwent a 51Cr-EDTA basal permeability test and the same test after challenge with indomethacin 125 mg p.o. RESULTS: Small intestinal permeability was the same in smokers (median 1.22%; IQR 1.00-1.58) and nonsmokers (1.24%; 0.94-1.66). Basal small intestinal permeability was lower in females (1.09%; 0.87-1.33) than in males (1.48%; 1.18-1.88). Indomethacin challenge increased permeability by 110% (71-141) in smokers, vs. 156% (78-220) in the nonsmokers (P=0.04). CONCLUSION: Smoking reduces the effect of NSAID on small intestinal permeability. It is therefore unlikely that the adverse effect of smoking on Crohn's disease is related to its influence on intestinal permeability.

Severe knee pain as the single symptom of CMV infection in acute ulcerative colitis treated with cyclosporine.

We describe a case of systemic cytomegalovirus (CMV) infection in an ulcerative colitis patient admitted to the hospital for an acute flare-up of his colitis. He was treated with combination immunosuppressive therapy including i.v. cyclosporine and corticosteroids and PO azathioprine. Severe bilateral stabbing knee pain was the only manifestation of CMV disease, which quickly responded to adequate antiviral therapy.