Defective post-transcriptional processing of MUC2 mucin in ulcerative colitis and in Crohn's disease increases detectability of the MUC2 protein core.

Ulcerative colitis (UC) and, to a lesser extent, Crohn's disease (CD) are associated with a reduction of the protective mucus layer in the large intestine; the role of this alteration in the pathogenesis of either disease is, however, not clear. To learn more about the molecular mechanism of the alteration of the mucus layer, the expression of the main intestinal mucin, MUC2, was investigated in relation to inflammation and dysplasia. Formalin-fixed, paraffin-embedded biopsies from 70 patients with UC and 16 patients with CD, and 13 biopsies from normal colonic mucosa, were used for detection of MUC2 mRNA by in situ hybridization with the SMUC41 probe, and MUC2 protein by immunohistochemistry with the antibody CCP58. The steady-state concentration of MUC2 mRNA was not affected by UC or CD. By contrast, the amount of the detectable MUC2 protein, assessed as the immunoreactive score (IRS), was significantly (p<0. 0001) increased in UC (IRS=8.0+/-3.8) and CD (8.0+/-3.7), compared with the normal colonic mucosa (IRS=2.0+/-1.5). This alteration occurred in the inactive phase of inflammation and persisted in the active phase of the disease. It was also observed during bacterial or protozoal inflammation (n=7). The IRS values did not correlate with the grade of inflammation or dysplasia. Simultaneous histochemistry with high iron diamine and immunohistochemistry indicated that the increase of detectable MUC2 is concomitant with low mucin sulphation in the same cells. These data indicate that the strong MUC2 protein staining in colonic mucosa of patients with UC or CD is due to a long-term alteration of the post-transcriptional modification of the MUC2 molecule, leading to its better detectability by the anti-MUC2 antibody CCP58. This alteration, induced by the inflammatory process, may affect the gel thickness and may contribute to a protracted autoimmune response.

[Duodenal ulcer - multicenter double-blind study with proglumide]. / Ulcera duodeni - multizentrische Doppelblind-Studie mit Proglumid.

In a randomised multicenter double blind study we investigated the healing-rate with proglumid and an antacid drug, studying 70 in- and outpatients with florid duodenal ulcer. We evaluated the size and depth of 59 chronic duodenal ulcers in 52 patients with endoscopic and x-ray-investigations before and after four-week-treatment. Inpatients of the proglumid-group had a significant higher healing-rate than inpatients in the antacid-group (95% against 70%, p less than 0.05). As found in endoscopy the outpatients in the proglumid-group had a higher healing-rate, but because of the smaller number of patients the difference was not significant. Summarized the in- and outpatients, the proglumid-group had a healing-rate of 83%, the antacid-group of 60% (p less than 0.05). Bigger ulcers with a size more than 120 mm2 at the beginning showed a significant better healing with proglumid than with the antacid-drug (t/2 = 14.6 resp. 24.6 days). With x-ray-examination we could not find differences of healing between the two groups, but younger patients often were not examined. The symptoms of patients did not show a significant difference during the healing-course. We could not find any side-effects. Proglumid is an effective drug for the healing of chronic duodenal ulcers.