Masaru Okuhira

Role of endothelin and platelet-activating factor in indomethacin-induced gastric mucosal injury in rats.

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.

Role of Endogenous Endothelin in Gastric Mucosal Injury Induced by Hemorrhagic Shock in Rats

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.

Cell proliferation kinetics in acetic acid-induced gastric ulcer evaluated by immunohistochemical staining of proliferating cell nuclear antigen.

A monoclonal antibody to proliferating cell nuclear antigen (PCNA) has been previously shown to be capable of identifying proliferating cells. We investigated proliferative activity in the healing process of acetic acid-induced gastric ulcer by immunohistochemical staining of PCNA and 5-bromo-2-deoxyuridine (BrdU), and the two methods were compared. Cell proliferative activity of regenerated mucosa around ulcers showed continuous acceleration for 42 days, and PCNA-labeled cells had stained nuclei as clearly discernible as those of BrdU-labeled cells. In addition, immunohistochemical staining of PCNA provided reproducible and quantifiable results without the requirement of pretreatment. We conclude that immunohistochemical staining of PCNA may represent a useful technique for analysis of proliferative activity during healing of gastric ulcers.

DIFFUSE CALCIFICATION IN GASTRIC CANCER

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.

Cell Proliferation Kinetics in the Marginal Mucosa of Gastric Ulcer Evaluated by Immunostaining of DNA Polymerase α

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 alpha 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.

Acute Gastric Lesions Induced by Transcatheter Arterial Embolization and Intra-arterial Infusion Chemotherapy for Hepatocellular Carcinoma

We performed an endoscopic study of the acute gastric lesions induced by transcatheter arterial embolization (TAE) and infusion chemotherapy (one shot infusion: OSI). Forty‐eight patients with primary hepatocellular carcinoma were investigated, and of them, 25 received TAE and 23 were treated with OSI. Endoscopy was performed within 1 week both before and after therapy and any gastric mucosal changes were noted. Before treatment, all patients had gastric lesions such as redness, erosion, hemorrhage and ulcer. These lesions were exacerbated or new lesions appeared after both TAE and OSI in about 50% of the subjects, and no significant difference in the incidence of lesions was observed between these two treatments. Moreover, there was no significant correlation between the exacerbation or new appearance of gastric lesions and the Childs classification, the catheter position, or the presence or absence of A‐P shunt or portal thrombus.

Endoscopical determination of gastric mucosal blood flow by the crossed thermocouple method

SummaryA crossed thermocouple method in combination with endoscopy was applied to determine the blood flow rate of the human gastric mucosa. Determination was carried out with 11 healthy control subjects at 8 sites of the stomach. The blood flow rates at all sites in the corpus were found to be higher than those at the antrum. In subjects less than 50 years old the blood flow rate in the corpus was higher than in older subjects. These results were in agreed well with those obtained by the hydrogen gas clearance method, which is widely adopted clinically. The crossed thermocouple method is easily applicable to all sites in the gastric mucosa and the time required for the assay is very short. This method dose not require the inhalation of hydrogen gas which is necessary for the hydrogen gas clearance method and which is possibly harmful to humans. Although the values obtained by the crossed thermocouple method are relative to the value at a certain fixed site, this method will holds great potential for the determination of gastric mucosal blood flow rate.