SUMMARY This study confirms previous reports that satisfactory gastric acid secretory responses to intravenous administration of histamine, carbachol, and gastrin can be obtained.Bilateral castration of the male rats significantly reduced acid gastric secretory responses to carbachol but not to histamine.Ovariectomized rats treated with 1 7B-oestradiol (short-term treatment) showed a statistically significant reduction in gastric acid secretion induced with all the secretagogues, but the results when rats were treated with testosterone were inconsistent. In animals given gastrin or histamine gastric acid secretion was reduced and was of statistical significance with gastrin (0.02 < p < 0(05) but not with histamine (0.05 < p > 0.1).It is concluded that a high oestrogen blood level is capable of inhibiting effectively acid gastric secretion in both sexes except that a higher level of blood oestrogen is required in the male. Tite results showed further that of all the sex hormones used, only oestrogen had a significant effect on gastric acid secretion.It has long been recognized that peptic ulceration rarely occurs in human pregnancy. This has naturally focused attention on gastric secretory activ,ity during this period, and there have been reports of diminished secretion of pepsin and hydrochloric acid during pregnancy (
A method is described for the partial purification of hog's antral gastrin by gel filtration and ion-exchange chromatography. Gastrin was assayed by its effect on the pH of the effluent fluid from the perfused lumen of the stomach of the anaesthetized rat. The latency of the response to gastrin given intravenously was shorter than the latency to a similar dose of histamine. The response to gastrin injected into the arterial circulation of the stomach appeared sooner than the response to gastrin injected intravenously. Iproniazid and aminoguanidine potentiated responses to gastrin. Incubation in vitro with monamine oxidase or diamine oxidase did not inactivate gastrin. Chlorpromazine and bromolysergic acid diethylamide, in doses which enhance the effects of histamine on acid gastric secretion, did not affect responses to gastrin.
In anaesthetized rats in which the lumen of the stomach was perfused with 0.001 to 0.00025 N-sodium hydroxide solution and the pH of effluent fluid was recorded continuously, intravenous administration of chlorpromazine caused transient inhibition of acid secretion. After acid secretion had returned to the control level the responses to histamine were greater than those before chlorpromazine was given. Aminoguanidine, iproniazid and bromolysergic acid diethylamide also potentiated the effect of histamine on acid secretion but the initial inhibition was absent. Indirect evidence from experiments in which mixtures of andinoguanidine with chlorpromazine or bromolysergic acid diethylamide and of iproniazid with chlorpromazine or bromolysergic acid diethylamide were given, suggests that chlorpromazine and bromolysergic acid diethylamide enhance responses to histamine by inhibition of imidazole-N-methyl transferase.
SUMMARY This study confirms the preliminary reports that Duogastrone effectively controls the symptoms of duodenal ulceration and appears to hasten healing. In a double-blind trial, 14 patients with active duodenal ulcers were treated with Duogastrone capsules, one four times daily, half-an-hour before meals, while a comparable control group of 14 patients was treated similarly with a placebo containing magnesium trisilicate. Treatment continued for 12 weeks with clinical assessments fortnightly and a radiological assessment at the start and at the end of treatment.Only one of the 14 patients receiving Duogastrone did not respond. The remaining 13 showed marked clinical improvement with complete relief of pain and ceased to require supplementary antacids. Radiological evidence of healing or marked improvement was seen in eight of the 14 patients.None of the patients in the control group showed any marked improvement either of pain or tenderness and no changes were detectable by radiology. Patients in this group showed no reduction in their demand for supplementary antacids to relieve symptoms. No significant side effects were encountered.It is concluded that Duogastrone accelerates the healing of duodenal ulcer in ambulant patients and affords a much greater and more rapid relief of symptoms than does magnesium trisilicate.Many investigations have confirmed the value of carbenoxolone sodium tablets (Biogastrone) in the treatment of gastric ulcer in ambulant patients. The rate of healing in these trials has been comparable with bed rest in hospital. The tablets, however, have not been shown to have a therapeutic effect in duodenal ulceration. probably because carbenoxolone is rapidly absorbed from the stomach. The precise mode of action of the drug is not known but there is evidence that its effect is topical rather than systemic.A special positioned-release capsule (Duogastrone) has been designed which releases 50 mg carbenoxolone sodium directly into the duodenum in a concentrated form and preliminary studies
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