EDITORIAL SYNOPSIS A study of the effect ofpH on the stability and activity of pepsin showed that 70 % of maximal peptic activity was still present at pH 4 5 and that pepsin was irreversibly inactivated at pH 8. The clinical implications of these findings are discussed.The concept of peptic ulceration and its treatment is based on the ulcerogenic action of acid and pepsin (Card, 1952). It appears that pepsin plays the predominant role in this action (Schiffrin, 1940; Schiffrin and Warren, 1942; Le Veen, 1947), the acid merely providing the correct pH for optimal peptic activity. Consequently, it is of some importance to know the effect of pH on the peptic activity of pepsin. One of these effects, the effect of pH on peptic activity, has been adequately studied (Christensen, 1955; Taylor, 1959a, b and c); the effect of pH on enzyme stability has received little attention apart from the observations of Langley in the last century (Langley, 1881a and b) and those of Northrop, Kunitz, and Herriott (1948). As both of these effects are of considerable importance in clinical gastroenterology, the present study was undertaken of the effect of pH on the stability and activity of pepsin. METHODSEFFECT OF pH ON THE STABILITY OF PEPSIN Solutions of pepsin were incubated at 37°C. for 10 minutes at varying pH levels, then titrated to pH 2 and peptic activity estimated using the radioiodinated serum albumin method (Klotz and Duvall, 1957;Piper, 1960). The peptic activity in these reaction mixtures was compared, after corrections had been made for the dilution involved in the back titration, with the peptic activity of a standard solution that had not been incubated at any different pH. The solutions of pepsin used were Parke Davis reference pepsin (400 mg. %) and unpurified solutions of human pepsin obtained from the homogenate of human gastric fundic mucosa.As the time the pepsin was at the high pH could be crucial, a solution of Parke Davis reference pepsin and of human pepsin was incubated at pH 7-2 for varying times (1, 2-5, 5, 10, 20, 40, and 60 min.) and the effect on peptic activity on restoration to pH 2 determined as above.EFFECT OF pH ON PEPTIC ACTIVITY A pH activity curve for human pepsin was determined using radioiodinated serum albumin as substrate and the method previously described (Piper, 1960). The pepsin was that of gastric juice obtained from a patient suffering from a gastric ulcer. The pH of the reaction mixture was adjusted using varying proportions of buffers, 01 M glycine HCl or 0-2 M acetate HCI buffers, as described by Taylor (1959a). RESULTSThe result of the studies on the effect of pH on peptic activity and stability is shown in Figure 1. The pH stability curve in this figure represents that of pepsin in human fundic mucosa; Parke Davis reference pepsin gave an identical curve. These results show that pepsin is stable at pH ranges as high as pH 6. Above this pH, pepsin is rapidly irreversibly inactivated and elevation of pH of the reaction mixture to pH 8 results in complete inactivation of pepsin...

Background-Eradication ofThere was a significant diVerence (p < 0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant diVerence (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less eVective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no diVerence among the treatment groups with regard to the incidence and severity of adverse events reported. Conclusions-All four treatment regimens were safe and eVective in eradicating H pylori in the patient population studied. LAC was the most eYcacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients. (Gut 1997; 41: 735-739)

Omeprazole blocks the action of H+,K+-ATPase in the gastric mucosa and thus inhibits the secretion of hydrochloric acid. We conducted a double-blind multicenter study (45 centers in 13 countries) of 602 patients with benign gastric or prepyloric ulcers to compare the effectiveness of omeprazole (20 mg once daily, 203 patients, or 40 mg once daily, 194 patients) and ranitidine, an H2-receptor antagonist (150 mg twice daily, 205 patients) in promoting ulcer healing and to evaluate the pattern of ulcer relapse during a six-month follow-up. Healing occurred at four weeks in 80 percent of the patients receiving 40 mg of omeprazole, 69 percent of those receiving 20 mg of omeprazole, 69 percent of those receiving ranitidine. At eight weeks, the corresponding figures were 96, 89, and 85 percent. A multivariate analysis of ulcer healing showed that at four weeks the ulcers of significantly more patients receiving omeprazole had healed as compared with patients receiving ranitidine (omeprazole, 40 mg, vs. ranitidine, P less than 0.0005; omeprazole, 20 mg, vs. ranitidine, P = 0.01). At eight weeks, the 40-mg dose of omeprazole was significantly more effective than ranitidine (P = 0.001) or the 20-mg dose of omeprazole (P = 0.03). Ulcer symptoms were relieved faster with omeprazole. In 68 patients receiving concurrent nonsteroidal antiinflammatory drugs, the healing rates at four weeks were 81 percent in the group receiving 40 mg of omeprazole, 61 percent in the group receiving 20 mg, and 32 percent in the group receiving ranitidine; at eight weeks, the corresponding figures were 95, 82, and 53 percent. During the six-month follow-up period (without treatment), significantly more patients in the omeprazole groups were free of symptoms and ulcers than in the ranitidine group. We conclude that in the dose used, omeprazole is superior to ranitidine in the treatment of benign gastric ulcers.

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