Administration of dextran sulphate sodium to animals induces acute colitis characterized by infiltration of large numbers of neutrophils into the colonic mucosa, which histologically resembles human active ulcerative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of ulcerative colitis. This study was intended to clarify their roles by using this animal model. First, possible sources and species of reactive oxygen metabolites were determined using luminol-dependent chemiluminescence with addition of enzyme inhibitors and reactive oxygen metabolite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered RP-3, a monoclonal antibody capable of selectively depleting neutrophils, and taurine, a hypochlorous acid scavenger, to rats treated with dextran sulphate sodium. Addition of azide, taurine, catalase, superoxide dismutase and dimethyl sulphoxide into colonic mucosal scrapings significantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hypochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radical are generated by the inflamed colonic mucosa. Intraperitoneal injections of RP-3 significantly suppressed bleeding, tissue myeloperoxidase activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important role in the development of this colitis and that hypochlorous acid might be one of the causes of tissue injury induced by neutrophils.

Administration of dextran sulfate sodium (DSS) solutions to rats induced colitis which resembled mucosal lesions of human ulcerative colitis. Recent reports have shown that some cytokines are related to the pathogenesis of ulcerative colitis. In the present report, we describe the production of two cytokines in colitis mucosa in this DSS model. Using a cytotoxicity assay and a radioimmunoassay, we observed significant increases in levels of tumor necrosis factor-α (TNF-α) in the colitis mucosa and detected interleukin-1α in the mucosa of 3 of 5 DSS rats and an increase in TNF-α had a tendency to be inhibited by treatment with FK 506. Immunohistochemical investigation of DSS mucosa showed that the number of activated T cells increased at the earlier phase of inflammation. Luminol-dependent chemiluminescence values and myeloperoxidase activities were increased in the late phase of colitis and were suppressed by the FK 506 treatment. These findings may support the role of TNF-α and T-cell activation in the pathogenesis of DSS colitis.

EPBD has little risk of bleeding. The technique removed small bile duct stones just as easily as did EST. These two procedures had approximately the same risk of pancreatitis and incidence of recurrent bile duct stones. Therefore, both procedures appear to be appropriate treatments for small bile duct stones. Whether or not EPBD becomes an established treatment will depend on further long-term studies.

EPBD has a possibility of suppressing bacterial contamination of the biliary tract compared with EST in patients with small stones. A large, long-term follow-up, randomized, controlled trial is necessary to clarify whether this benefit of EPBD reduces late complications.

EPBD produced significantly better long-term outcomes than EST in patients with small bile duct stones.