Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers due to inhibition of prostaglandin production. Prostaglandins have an influence on physiological gastrointestinal motility, but the relationships between NSAID-induced gastric ulcer, gastrointestinal motility and motilin are unknown. Fifteen dogs were allocated randomly to three groups in which either gelatin, meloxicam or indomethacin was administered. Fecal occult blood and gastrointestinal motility were monitored continuously for 6 days. In addition, analyses of the plasma motilin concentration, gastrointestinal endoscopy and gastric emptying, and detection of motilin cells were performed. Gastrointestinal motility was disturbed in the indomethacin group, presenting as disappearance of interdigestive migrating contractions (IMCs) 3 days before gastric ulcers were detected. Delayed gastric emptying and hypermotilinemia were observed significantly more often in the indomethacin group compared with the other groups. Motilin cell-crypt/villi ratio in the indomethacin group significantly decreased in the duodenum and jejunum, compared with the other groups. No significant changes in any tests were observed in the meloxicam group, when compared with the gelatin group. These findings suggest that the disturbance of IMCs caused by hypermotilinemia, with changes in motilin cell distribution, and delayed gastric emptying induced by indomethacin may contribute to the development of gastric ulcers.

The aims of the present study were to investigate the incidence of adverse effects of thioureylene antithyroid drugs and to see if there were any factors related to the development of the adverse effects. Methimazole or propylthiouracil was administered to 151 patients with Graves disease; 76 untreated cases and 75 treated cases. The overall incidence was 22.4% among the 76 untreated cases. The incidences were 26.7% (13/45 cases) for methimazole and 16.1% (5/31 cases) for propylthiouracil, respectively, which were significantly higher than those previously reported. Fourteen out of 17 cases with the adverse effects were given the other thioureylene. The successive incidence of the adverse effects was 28.6% (4 cases), which was not significantly different from that under the drug of first choice. The result suggests that methimazole and propylthiouracil may not have cross-reaction each other. On the other hand, antinuclear antibody and anti-DNA antibody became positive in 2 out of the 4 cases. It would be a significant phenomenon, since antinuclear antibody was positive in only 3% of cases before the drug treatment. Thus, an immunological mechanism seemed to be involved in the problems, although there was no correlation between antithyroid autoantibodies and the development of the adverse effects. The adverse effects were observed within 2 months of administration of less than 250 tablets in total in most of the cases. The results imply that allergic mechanism rather than accumulating or toxic effect may concern the development of adverse effects of the thioureylenes.