H. Arakawa

COMPARATIVE STUDY ON HISTOLOGICAL CHANGES AROUND ULCER LESION AND SECRETORY FUNCTION BETWEEN PEPTIC ULCER AND ULCERATIVE TYPE OF EARLY CANCER OF THE STOMACH

SummaryPeptic ulcer and early cancer of the stomach possessing ulcer lesion of similar size locating near angular incisure were compared concerning histological changes around ulcer lesion and secretory function with the following conclusions. In peptic ulcer the restriction in the development of ulcer size is accompanied by the relatively stationary localized mucosal atrophic changes around ulcer lesion, while in gastric carcinoma the advancement of carcinomatous ulcer lesion brings the development of mucosal atrophic changes around lesion in degree and extent. Such findings may be interpreted as the evidence that some part of mucosal atrophie changes around ulcer lesion are secondary to ulcer lesion and the nature of ulcer lesion decides the future course of atrophie changes, although such histological changes proceed unevenly from direction to direction with marked individual variation. As to secretory function of the stomach no essential difference was found in maximal acid output (MAO) and pepsin output after maximal stimulation between two clinical entities. The correlation was recognized between the degree and the extent of mucosal atrophie changes and the degree of secretory disturbance in each individual case.

Study of the inhibitory action of prostaglandin on gastric secretion in rat and man

Synthesized prostaglandin Et (PGEt) was investigated regarding its inhibitory effect on gastric juice secretion and experimental gastric ulcer formation. Continuous increase of gastric juice secretion was produced by cont inuous injection of histalog to the dogs with pylorus ligation. The gastric juice secretion was remarkably inhibited by int ravenous injection of PGE1, 2/*g/kg/min, for 20 minutes. The secretion star ted again 20 minutes after discontinuation of the injection. Gastric ulcer was produced experimental ly on ra ts to observe the inhibitory effect of PGE1. PGE1 remarkably inhibited gastric juice secretion to produce Shay s ulcer and Reserpin ulcer, but only mildly to produce steroid ulcer.

The study on the metabolism of gastrin and its related substance

Using Lais method modified by adoption of Brom Cresol Green as the indicator to detect the terminal point of acid secretory response of rat s stomach to A0C tetrapeptide which was given via femoral vein or superior mesenteric vein, acid output in each method of administration was compared with following conclusions. 1) The decrease in acid output was observed in the administration of AOC tetrapeptide via sup. mesent, vein as compared with via femoral vein. The data was interpreted to support the livers role in inactivation of AOC tetrapeptide. 2) The pattern of this decrease is not simple irrespective of method of experiment used namely various dosis of stimulus given in the certain time and the certain dosis of stimulus given in the different time, suggesting that the mechanism of inactivation of AOC tetrapeptide in the liver is complicated. 3) The possibility that such complicated mechanism of inactivation may be working against endogenous gastrin physiologically in the liver is pointed out. This may necessitate to consider the possible secondary hypergastrinemia due to decreased inactivating ability in the liver as the aetiological factor of peptic ulcer which is known to occur frequently in various liver diseases in addition to the primary hypergastrinemia due to increased release of gastrin into blood stream.

Study on the acting mechanism and the clinical effect of antipeptic agent for the treatment of peptic ulcer (II)

In order to evaluate the usefulness of sulfated polysaccharide for the t r ea tmen t and /o r the prevent ion of the recurrence of peptic ulcer, it is essent ia l to see whe ther i ts inhibi t ing act ion is displayed upon the proteolytic act ivi ty of all enzymes in nat ive gast r ic juice. Data presented dealt wi th the effect of Dextran sulfate on pH activi ty curve of proteases in nat ive gast r ic juice, ur ine and crystal l ized pepsin, showing tha t proteolytic act ivi t ies of all enzymes in these fluids are inhibi ted wi thout exception and also no difference is observed between pepsinogen and pepsin concerning the mode of inhibi t ion. The clinical s tudy revealed tha t single admin i s t ra t ion of Amylopect ine sulfate yielded 59.1% of complete heal ing of peptic ulcer judged by both X-ray and gastroscopic examinat ion , giving the impress ion tha t the cl inical effectiveness of both Dext ran sulfate and Amylopect ine sulfate is a lmost same. Both healed and unhealed cases were examined in detail concern ing fac tors influencing prognosis in peptic ulcer.

Treatment of peptic ulcer with various antipeptic agents

Using various sulfated polysaccharides the mechanism of antipeptic activity, the method of clinical administration and the clinical effect for the t reatment of peptic ulcer were studied and the following conclusions were obtained. (1) The autipeptic activity of sulfated polysaccharide is believed to base not only on the direct inhibition of peptic activity due to the binding of pepsin itself, but also on the protection of substrate f rom peptic digestion by means of strong binding of the lat ter under the acid condition as proved by means of paper electrophoresis. This fact suggest that sulfated polysaccharide may protect the ulcer f rom peptic digestion through its binding of protein substance covering the ulcer crater. (2) As the result it is recommended to adminis ter the drug clinically at the time when the stomach is empty and it is considered that the simultaneous administrat ion of anticholinergic agent will enhance the clinical effect. On the contrary the simultaneous administration of ant acid and antipepsin should be avoided because of the fact that the elevation of intragastric pH with ant acid decreases the action of sulfated polysaccharide. (3) It is desirable to develop the easy water soluble but not or hard absorbable sulfated polysaccharide in order to get maximum clinical effect. Because of the limitation of choice the daily dose of 2 g. of Dextran sulfate was used clinically yielding about the same clinical effect as hi therto used drugs of different mechanisms. It s future is believed to be hopefu l (4) The appearance of antipeptic agent which acts under acid circumstance and should not be used together with ant acid urges the reevaluation of the pathophysiologic basis of peptic ulcer in order to establish the direction of t rea tment of each individual patient suffering from peptic ulcer. At least it can be said safely at present t ime sulfated polysaccharide is favoured for the t reatment of the case with recurring ulcer af ter gastrectomy.