We examined the role of endogenous endothelin in the pathogenesis of hemorrhagic shock-induced gastric mucosal injury in rats. Animals were bled to induce hypotension (20-30 mm Hg) for 20 min and the shed blood was retransfused. Rats were sacrificed at the end of hypotension, 20 min, and 60 min after retransfusion, respectively. Gastric erosions were induced with this experimental protocol. The total area of erosions was minimal only at the end of hypotension, and increased time-dependently after blood retransfusion. Plasma endothelin concentration significantly increased at the end of hypotension and persistently increased after retransfusion, whereas in gastric endothelin concentration a significant increase was observed at 60 min after retransfusion. The gastric mucosal hemodynamics as assessed by continuous measurement with reflectance spectrophotometry showed ischemia associated with congestion after retransfusion. Treatment with a monoclonal antibody against endothelin (0.2 mg/100 g BW/h) prevented these hemodynamic disturbances, rendering a significant decrease in the total area of erosions at 20 and 60 min after retransfusion. These results strongly suggest an important role of circulating endothelin in the pathogenesis of hemorrhagic shock-induced gastric mucosal injury through mucosal microcirculatory perturbation.

The current study was designed to investigate the role of two potent vasoactive substances, endothelin (ET) and platelet-activating factor (PAF), in the pathogenesis of indomethacin-induced gastric lesions in rats. Treatment with anti-ET antibody before indomethacin administration resulted in a significant decline in the total length of the lesions as determined by gross evaluation. In contrast, CV-6209, a specific PAF antagonist, had no effect on the total length of the lesions. The results strongly suggest the incorporation of endogenous ET in the mechanism of gastric damage after indomethacin administration.

No abstract

The progressive expansion of calcification into the wall of the stomach and peritoneal metastatic foci was observed in a 31-year-old female with Borrmann type 4 calcified advanced gastric cancer. Despite treatment with systemic lentinan, uracil tegaful and mitomycin C, together with intraperitoneal injections of mitomycin C, OK-432 and prednisolone, the patient died 27 months after first presentation. The case provided a useful means of studying the mechanism of calcification.

We studied the proliferative ability of the marginal mucosal cells surrounding the ulcer in the healing processes of gastric ulcers. We obtained a labeling index (LI) at the neck and generative zone of gastric pit using a monoclonal antibody against DNA polymerase α for tractable and intractable gastric ulcers located at the fundic mucosa during each endoscopic stage. The LI during the healing stage was higher than that during the active stage in both the tractable and intractable cases. However, in each stage, the LI of the tractable gastric ulcers was higher than that of their intractable counterparts. Finally, we analyzed the LI in tractable gastric ulcers after setting two groups: one treated with anti-ulcer drugs and the other untreated. There were no significant differences between these two groups. We believe that investigation of proliferative abilities in the marginal mucosa of gastric ulcers is important to understand the nature of gastric ulcers and to assess therapeutic efficacy.