Isamu Morita

Oral administration of mesalazine protects against mucosal injury and permeation in dextran sulfate sodium-induced colitis in rats

Abstract Objective. Mesalazine, from which 5-aminosalicylic acid is released, is a therapeutic drug for inflammatory bowel disease. There has been no study concerning the effect of orally administered mesalazine on dextran sodium sulfate (DSS)-induced colitis in the rat model of ulcerative colitis. Material and methods. Colitis was evaluated by means of the length of the colon, white blood cell count (WBC), tissue myeloperoxidase (MPO) activity, and histological inflammation scores. Colonic mucosal permeation was evaluated using Evans blue. The localization of a tight junction protein, occludin, was evaluated immunohistochemically and examined using confocal laser scanning microscopy. Results. Mesalazine significantly improved changes in the length of the colon, tissue MPO activity, WBC, and the histological inflammation score as compared with DSS-induced colitis. Furthermore, the drug completely inhibited the increased permeation in DSS-induced colitis in rats. The immunofluorescence signals of occludin were disrupted and irregularly distributed in DSS-induced colitis, while the signals appeared as a typical reticular pattern but with reduced intensity by the administration of mesalazine, without any reduction in the protein content. In addition, the oral administration of mesalazine significantly improved mucosal permeation, thereby protecting the intestinal mucosa against injury in DSS-induced colitis in rats. Conclusions. These findings suggest that the recovery of mucosal impairment due to treatment with mesalazine may be associated with the protection of the tight junction protein occludin in DSS-induced colitis.

Double doses of secretin contribute to diagnosis of Zollinger-Ellison syndrome in secretin and selective arterial secretion injection tests- : A case report

Zollinger–Ellison syndrome (ZES) involves hypergastrinemia produced by a gastrin-secreting tumor of the pancreas or duodenum. A fasting gastrin level higher than 1000 pg/ml and a basal acid output greater than 15 mEq/hr in patients with recalcitrant peptic ulcers are diagnostic for ZES (1). In the absence of these data, provocative testing, such as the secretin and calcium tests, may be required. The secretin test offers the greatest sensitivity and specificity. Unfortunately secretin tests can be negative in a significant population of patients with ZES (2, 3). Previous studies demonstrated that the secretin test is positive in 87 to 93% of all patients diagnosed with ZES (1). In the standard secretin test, an intravenous bolus of 2 μg/kg of secretin, where 1 μg is equivalent to 2 U, is infused (1). However, Matsui et al. reported that a secretin dose of 6 U/kg proved more useful than the standard 3 U/kg dose in four patients diagnosed with ZES (4). The selective arterial secretion injection test (SASI) is useful in localizing gastrinomas (5–8). The standard dose of secretin for the SASI is usually 3 U/kg (5, 6) or 30 U (7, 8). In our patient, diagnosed with hypergastrinemia and recalcitrant peptic ulcer, the secretin and SASI tests yielded negative outcomes using 3 U/kg of secretin but were positive when 6 U/kg of secretin was

The Effect of Polyethylene Glycol-Electrolyte on Dextran Sulfate Sodium-Induced Colitis in Rats

The Effect of Polyethylene Glycol-Electrolyte on Dextran Sulfate Sodium-Induced Colitis in Rats Chifumi Yamamoto, Kunihiko Aoyagi, Yoshihiro Hayashi, Isamu Morita, Shotaro Sakisaka Background & Aims: Polyethylene glycol-electrolyte (PEG-EL) is the most commonly used agent for mechanical bowel cleansing. Adverse events related to PEG-EL have included serum electrolyte disturbance, gastrointestinal discomfort and rectal mucosal abnormalities. However, there have been few studies evaluating the effect of PEG-EL on colitis, such as ulcerative colitis. The aim of this study was to evaluate the safety of PEG-EL in cases of both normal colon and dextran sulfate sodium (DSS)-induced colitis. Methods: Exp. 1; Twenty Male Wistar rats were divided into two groups, the DSS-induced colitis group and the normal colon group. Colitis was induced by administering 3% DSS in drinking water over a period of 6 days. Following the administration of DSS or distilled water, each group received either PEG-EL (Niflec , Ajinomoto Pharma, Tokyo, Japan) or distilled water for 14 hours (each group, n Z 5). Colitis was evaluated by tissue myeloperoxidase (MPO) activity and by the inflammation score as described by Cooper. A blood sample was taken from the portal vein to measure WBC, RBC and Hb. Exp. 2; The effect of PEG-EL in the DSS-induced colitis group (each group, n Z 5) was evaluated in the same way as in Exp. 1, 12, 24 and 48 hours after the administration of either PEG-EL or distilled water. Results: Exp. 1; PEG-EL did not change the inflammation score in either the normal colon group (0 vs. 0) or the DSS-induced colitis group (2.15 G 0.6 vs. 2.2 G 0.6, p Z 0.89). Similarly, MPO activity, RBC and Hb showed no significant change. However, WBC was significantly increased in the DSS-induced colitis group which received PEG-EL (69,440 G 1971 vs. 51,040 G 2288, p Z 0.019). Exp. 2; At 12, 24 and 48 hours, there was no significant difference in either the inflammation score or MPO activity in any of the groups (see Table). However, there was a tendency to be a delay in decreasing MPO activity at 12 hrs in the DSS-induced colitis group which received PEG-EL (see Table). Conclusions: The present study shows that PEG-EL histologically affected neither the normal colon nor DSS-induced colitis. However, the improvement in colitis showed an inclination to be delayed in the DSS-induced colitis group which received PEG-EL. Consequently, it is essential that adequate care is taken when we use PEG-EL for patients with colitis.