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Background/aims: Butyrate and factor XIII may improve ulcerative colitis; they also affect tissue and serum transglutaminase levels. We investigated the therapeutic potential of sodium butyrate and factor XIII and the role of transglutaminase during mucosal repair in experimental colitis., Methods: Rats with induced colitis were treated with sodium butyrate, mesalamine, sodium butyrate plus mesalamine, or saline enemas. Thromboxane B2 was monitored as index of inflammation. In a fifth group, the effectiveness of intravenous Factor XIII was assessed., Results: Sodium butyrate, alone or plus mesalamine, reduced histological activity from 13.7 +/- 1.7 (saline) to 2.5 +/- 1.3 and 2.3 +/- 1.1 (P < 0.01), respectively. Transglutaminase, reduced in the colons of the saline group (783 +/- 157 vs. normal 1800 +/- 192 mU/g; P < 0.01), returned toward normal values in the sodium butyrate or sodium butyrate plus mesalamine groups (1390 +/- 228 and 1226 +/- 172 mU/g, respectively; P < 0.01 vs. saline). Furthermore, sodium butyrate plus mesalamine reduced thromboxane B2 levels by day 5 (0.92 +/- 0.16 vs. saline 1.85 +/- 0.34 ng/mL; P < 0.05). Factor XIII therapy improved the histological picture (2.7 +/- 2.1 vs. saline 13.8 +/- 1.7; P < 0.01) and increased transglutaminase levels both in serum (2.81 +/- 0.11 vs. saline 1.45 +/- 0.09 mU/mL; P < 0.01) and in colon (1503 +/- 127 vs. saline 747 +/- 103)., Conclusions: Sodium butyrate and factor XIII improve colitis, sodium butyrate plus mesalamine reduce early thromboxane B2 synthesis, and transglutaminase(s) plays a role in ulcer healing.

The human colon carcinoma cell line CaCo-2, grown in vitro under standard culture conditions and in the absence of differentiation inducers, spontaneously exhibits structural and functional characteristics of mature small bowel enterocytes. Differentiation is complete at late confluency. High activities of ornithine decarboxylase and diamine oxidase are present in enterocytes. Although these enzymes are involved in polyamine metabolism and therefore in cell replication, their function in small bowel epithelium remains to be defined. In this study ornithine decarboxylase and diamine oxidase activities were assessed in CaCo-2 cells at different stages of proliferation and differentiation. Diamine oxidase was also assayed in spent culture media to assess its spontaneous release by CaCo-2 cells. The trigger effect of medium replacement on ornithine decarboxylase activity was also investigated. Cell growth and cell cycle kinetics were determined by hemocytometric cell count and [3H]thymidine labeling index. Sucrase activity was assayed to evaluate brush-border functional maturation. Elevated ornithine decarboxylase activity was recorded during the replication phase (highest value 0.3 +/- 0.02 U/mg) characterized by high thymidine labeling index (43%), and was greatly enhanced by medium replacement (2.1 +/- 0.3 U/mg). Diamine oxidase activity was low in both cells and medium during the active phase of cell growth, and during the differentiation period it progressively increased (highest value 499 +/- 78 U/mg) along with sucrase activity. The high diamine oxidase activity recorded in the medium (highest value 1292 +/- 310 U/ml) and the evidence of diamine oxidase secretion through the basolateral membrane of the cells cultured on porous filters support the hypothesis of an extracellular role of intestinal diamine oxidase. The CaCo-2 cell line, which shows several analogies with small bowel enterocytes, can be proposed as an interesting in vitro model for studying many aspects of cell replication and differentiation depending on polyamine metabolism.

Diamine oxidase (DAO) is an enzyme located almost exclusively in villus tip enterocytes of mammals. Its plasma activity, normally very low, is enhanced by intravenous heparin, which releases the enyzme from small bowel enterocytes into the blood. Plasma postheparin DAO (PHD) values have been shown to be significantly reduced in patients with malabsorption and villous atrophy and inversely correlated with 24-h fecal fat, thus suggesting that PHD reflects the mature enterocytic mass. We have assayed PHD in 51 patients with small bowel Crohn's disease by measuring the area under the plasma DAO curve over a 120-min period after an intravenous bolus of 15,000 IU of heparin. Postheparin plasma DAO was significantly lower (p less than 0.001) in patients (328 +/- 175 U/ml.min) than in 20 normal subjects (508 +/- 101 U/ml.min; range, 391-749). Postheparin diamine oxidase values were inversely correlated with Crohn's disease activity index (CDAI), but no correlation was found with extent of disease assessed radiologically by either double-contrast small bowel enema or barium meal follow-through. In 6 patients with active disease (CDAI, 297 +/- 99) and low PHD values (188 +/- 100 U/ml.min), the assay was repeated after a clinically effective course of antiinflammatory drugs. A significant increase in PHD values (388 +/- 112 U/ml.min) was observed (p less than 0.005). These data indicate that mucosal involvement is common in small bowel Crohn's disease and that PHD may be useful in assessing and monitoring mucosal damage in these patients.

Eighteen patients with irritable colon syndrome were treated with a new anticholinergic drug (prifinium bromide) and with a placebo in a 6-wk, randomized, double-blind cross-over study. The drug was orally administered in a daily dose of 90 mg before meals. Three manifestations (pain, flatulence, constipation, and/or diarrhea), scored weekly, were used as assessment criteria. Mean over-all ratings showed a difference in favor of the drug, and were statistically significant. Side effects were rare and mild. We have come to the conclusion that this anticholinergic drug may be of benefit to patients with pain-predominant forms of irritable colon syndrome.