H. Sakurada

Comparison of dose-response curves between acid and pepsin to betazole hydrochloride in the dog with gastric fistula

SummarySecretory responses to subcutaneously or intravenously administered betazole hydrochloride of graded doses were compared between acid and pepsin in the dog with gastric fistula. Although the dose related increments in acid and pepsin outputs were parallel in the range of lower doses than 2.0 to 3.0 mg/kg body weight of betazole hydrochloride, higher doses caused in decrease in pepsin output, but did not in acid output. It was pointed out that the dose of betazole hydrochloride that stimulates acid secretion maximally dose not correspond to the maximal stimulation for pepsin secretion in the dog.

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.

Histological status of gastric mucosa and secretory function of the stomach in atrophic gastritis

In order to know the relationship between histological status of gastric mucosa and secretory function of the stomach along the course of atrophic gastritis, cases known not to have any localized gastric diseases or other clinical entities including anemia, diarrhea etc. were studied. Scopic biopsy of the stomach was carried out at multiple sites, namely, two adjacent specimens were obtained at 12 sites. Gastric analysis was performed using betazole hydrochloride of the dose 2 mg per Kg of body weight as the maximal stimuli. Gastric juice was measured for three parameters, namely, titrable acidity, proteolytic activity and vitamin B12-binding activity. Furthermore the multiplicity of proteolytic enzyme in native gastric juice, gastric mucosa and urine was examined by means of agar electrophoresis. The gastrin concentration of fasting plasma was also measured by radioimmunoassay of two antibody system using Wilsons antisera. It was found that the advancement of atrophic changes of gastric mucosa brings not only the decrease in the secretory function of the stomach, but also the dissociation among three parameters, namely, acid, pretense and vitamin Blz binder in relation to the degree of sceretory disturbances especially at the late stage. It was shown that in general acid, tends to cease to be secreted first, then follows protease, and vitamin Ble binder remains long after the cessation of acid and protease secretion. The comparison of proteolytic activity between native gastric juice and urine obtained from the same subject also demonstrated that gastric protease can be excreted into urine after the cessation of its secretion into gastric lumen, suggesting the dissociation between synthesis and secretion of gastric protease in the late stage of atrophic gastritis. The examination of electrophoretic pattern of gastric protease, which showed the existence of eight fractions from fundic gland area, three fractions from pyloric gland area, suggested that such dissociation may exist among these fractions in relation to the degree of secretory disturbances during the course of atrophic gastritis, although many problems remain unsolved.

Measurement of plasma gastrin level by radioimmunoassay in various clinical entities

The plasma gastrin concentration was measured by radioimmunoassay of two antibody method in various clinical entities. Although the increase in age tended to elevate the fasting plasma gastrin level in general in cases without any localized organic diseases of the stomach, no difference was found among each decades in selected cases of endoseopically normal gastric mucosa and each remained as high as 163.70• Accordingly the age-effect of the fasting plasma gastrin level was regarded to reflect the difference of the incidence and the degree of atrophic gastritis in each decade. High degree of atrophic mncosal changes in advanced gastric cancer was also found to effect the fasting plasma gastrin level significantly. No essential difference was found concerning both the fasting and postprandial plasma gastrin level among eases of endoscopically normal gastric mucosa, gastric ulcer and duodenal ulcer. Besides the stomach, diseases of the kidney and liver especially the former were found to elevate the fasting plasma gastrin level.

Multiplicity of gastric proteases and its clinical significance

Bioptic specimens of gastric mucosa and 24 hours urine specimens collected from cases of histologically normal gastric mucosa or various gastric diseases were studied for multiple existence of acid proteases by means of agar gel electrophoresis. In cases of histologically normal gastric mucosa, mucosa obtained from fundie gland area, was proved to contain eight proteases, PI to PVII and slow mo,Ang protease (SMP), while in pyloric gland area three proteases, PVI, PVII and SMP, were found. In urine, however, four to three proteases, PII to PV, were demonstrated. These findings indicate that two groups of gastric proteases are elaborated in gastric mucosa characterized by the different distribution on gastric mucosa and the different attitude to renal excretion. Namely PI to PV were produced in fundic glandular area probably in chief ceils and excreted into urine, while PVI, PVII and SMP are elaborated in whole gastric mucosa probably in mucous neck cells and do not appear in urine. In a case of pernicious anemia only SMP was demonstrated in all mucosal specimens without any connection to the site of biopsy. In cases of early cancer of ulcerative type, mucosal specimen obtained at the edge of lesion does not show any proteolytic activity, while the full spectrum of proteases was found at the distant site from the lesion. The same findings were found in mucosal specimens around peptic 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.