Dipeptidyl peptidase-4 inhibitor anagliptin facilitates restoration of dextran sulfate sodium-induced colitis.

OBJECTIVE. Inflammatory bowel disease (IBD) is a chronic debilitating disease associated with severe damage to the intestinal mucosa. Glucagon-like peptide-2 (GLP-2) is a potent and specific gastrointestinal growth factor. GLP-2 released from enteroendocrine cells is inactivated by dipeptidyl peptidase-4 (DPP-4). The aim of this study was to examine whether the DPP-4 inhibitor anagliptin improves experimental murine colitis. MATERIAL AND METHODS. Male C57BL/6 mice aged 8 weeks were exposed to 1.5% dextran sulfate sodium (DSS) in drinking water for 7 days to induce experimental colitis. Anagliptin (0.1% in diet) was administrated from 2 days before the beginning of DSS to 7 days after the end of DSS. Changes in body weight and disease activity index were evaluated daily. Histological colitis severity, cellular proliferation and gene expression were determined in colonic tissues. RESULTS. Treatment with anagliptin clearly improved body weight loss and disease activity index in the recovery phase. Histological score in the DSS + anagliptin group at day 14 was significantly lower than that in the DSS alone group. Treatment with anagliptin increased the Ki67-positive rate at days 10 and 14, and tended to increase insulin-like growth factor-1 mRNA expression in the DSS + anagliptin group. CONCLUSION. In this model of experimental colitis, the DPP-4 inhibitor anagliptin facilitated the restoration of mucosal damage, thereby resulting in the acceleration of healing. These findings suggest a new and novel therapeutic approach for the treatment of IBD.

Intestinal cancers occurring in patients with Crohn's disease.

BACKGROUND AND AIMS: The number of patients with Crohn's disease (CD) and the number of cases of intestinal cancer associated with CD have both been increasing in Japan. However, the number of reported cases is lower than for ulcerative colitis-associated cancer. The aim of this study was to identify the clinical picture of CD-associated intestinal cancer in a consecutive series of patients with CD and to stress the importance of surveillance. METHODS: We enrolled 174 consecutive patients (130 men, 44 women, mean age 25 years) diagnosed with CD and investigated the development of intestinal cancer from October 1998 to July 2010. There were 104 cases of the ileocolitis type, 47 of ileitis, and 23 of colitis. RESULTS: Intestinal cancer developed in two male patients (1.5% of the total), whose respective ages at onset of CD were 41 and 19 years, and 55 and 37 years at onset of cancer. Both cases were of ileocolitis-type CD; one cancer developed in the rectum and the other in the small bowel, and both were accompanied by severe stricture. Histopathological results revealed well and moderately differentiated adenocarcinoma, respectively. CONCLUSIONS: Intestinal cancer developed in patients with ileocolitis-type CD of more than 10 years' duration. Our findings suggest that patients with chronic, widespread CD should be under cancer surveillance.

Enteral nutrition decreases hospitalization rate in patients with Crohn's disease.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disease with relapse and remission. CD patients are admitted to hospital when bowel inflammation flares up severely, which lowers their quality of life. Enteral nutrition (EN) with an elemental diet plays an important role in the treatment for CD patients in Japan, because of its few adverse effects, and it is thought to be effective in maintaining remission. We investigated the effectiveness of EN with an elemental diet with regard to the avoidance of hospitalization. METHODS: A total of 268 patients with CD who visited hospital from 2003-2008 were enrolled. The relationship between the caloric content of an elemental diet and hospitalization as an end-point was examined retrospectively using Cox regression analysis. Cumulative non-hospitalization rates were calculated by the Kaplan-Meier method. RESULTS: Of the 268 patients, 155 received an elemental diet providing 900 kcal/day or more. Among 237 patients with ileal involvement, 135 patients receiving an elemental diet providing 900 kcal/day or more showed a statistically significant improvement in cumulative non-hospitalization rate. Among 31 patients without ileal involvement, in contrast, the cumulative non-hospitalization rate did not differ among those receiving an elemental diet of less or more than 900 kcal/day. CONCLUSION: The use of an elemental diet of 900 kcal/day may be effective in avoiding hospitalization in CD patients with ileal lesions. This diet may be useful in improving the long-term convalescence of these patients.

Restriction-modification systems may be associated with Helicobacter pylori virulence.

Restriction-modification (R-M) systems are exclusive to unicellular organisms and ubiquitous in the bacterial world. Bacteria use R-M systems as a defense against invasion by foreign DNA. Analysis of the genome sequences of Helicobacter pylori strains 26 695 and J99 identified an extraordinary number of genes with homology to R-M genes in other bacterial species. All H. pylori strains possess their own unique complement of active R-M systems. All of the methylases that have been studied so far were present in all major human population groupings, suggesting that their horizontal acquisition pre-dated the separation of these populations. The two most strongly conserved methylase genes of H. pylori, hpy IM and hpy IIIM, are both preceded by alternative genes that compete for presence at their loci, and furthermore these genes may be associated with H. pylori pathogenicity. Further study should investigate the roles of H. pylori R-M systems.