The absorption of acetylsalicylic acid from the stomach in relation to intragastric pH.

A comparative study on the effect of a buffered (pH 6.5) and an unbuffered (pH 2.9) solution of acetylsalicylic acid (ASA) on gastric pH, gastric emptying, and gastric absorption of ASA was performed in 10 healthy volunteers. Gastric pH was recorded using radiotelemetry. Gastric emptying and gastric absorption was studied with an aspiration technique and phenol red as nonabsorbable marker. Administration of the unbuffered solution to the fasting subjects resulted in a gastric pH of about 2 and absorption of ASA from the stomach was found to occur. The buffered solution of ASA increased gastric pH to above 5 and gastric absorption of ASA was found to be significantly less than after the unbuffered solution. The buffered solution was emptied from the stomach more rapidly than the unbuffered one.     

Aspirin-induced gastric bleeding stops despite rising plasma salicylate

In 7 subjects, 100-ml successive portions of buffered acid (pH between 3.5 and 2.9) solutions of aspirin (1 g/liter) were instilled into the stomach and recovered after 10 min. Blood in the recoveries was estimated chemically. After there had been three successive increases in the rate of blood loss into the gastric lumen, typically rising from about 0.1 to 1 ml/day after about 80 min, buffered neutral solution of aspirin was instilled and recovered after 10 min. This was followed by a fall in the rate of blood loss into the gastric lumen which occurred despite a rise in the concentration of salicylate in the plasma from a mean of 55 mg/liter to 74 mg/liter. Under these conditions, salicylate in the plasma and acetylsalicylate in the gastric contents did not prevent gastric mucosal bleeding from falling to control levels within 50 min.     

Effect of acetylsalicylic acid on gastric mucosa. II. Mucosal ATP and phosphocreatine content, and salicylate effects on mitochondrial metabolism.

The effects of acetylsalicylic acid on gastric mucosal ATP and phosphocreatine and mucosal O2 consumption were studied using in vitro bullfrog gastric mucosa. Electrophysiological parameters (potential difference and resistance) changed rapidly after exposure to 10 or 20 mM acetylsalicylic acid at pH 3.0, 4.0, or 6.0 in the mucosal solution. ATP and phosphocreatine content decreased rapidly after exposure. Control mucosae contained 11.8 +/- 0.98 nmoles of ATP and 11.5 +/- 0.68 nmoles of phosphocreatine per mg of protein. ATP content decreased 21% and phosphocreatine decreased 45% after 15 to 30 min of exposure. Longer durations of exposure reduced both ATP and phosphocreatine to 10 to 15% of control levels. O2 consumption was increased during the first 15 to 30 min after exposure to acetylsalicylate. Longer durations of exposure reduced O2 consumption to near control levels. Study of isolated mitochondria confirmed that acetylsalicylate itself did not significantly affect mitochondrial respiration, respiratory control ratio, or ADP:O ratio. Salicylate had a biphasic effect which was concentration dependent. Salicylate initially stimulated and later inhibited mitochondrial respiration. Using various substrates the site of inhibition appeared to be located in the segment of the respiratory chain between coenzyme Q and cytochrome c1.     

Gastric emptying in relation to drug absorption

Summary 1. Test meals were given to healthy subjects, and the rate of gastric emptying was assessed from the volumes of the gastric contents recoverable after different periods.2. With test meals of 500 ml. containing a mixture of sodium citrate, sodium bicarbonate, and monocalcium phosphate, the rate of gastric emptying was more rapid than that of water and was largely independent of the concentration of the salts in the meal.3. Neither effervescence of the solutions nor the presence of acetyl-salicylic acid has any notable effect on gastric emptying.4. The influence of the volume of an ingested solution on gastric emptying, based on previous experiments, is outlined.5. These data are considered in relation to the volume and composition of a vehicle for drugs which are intended to reach the small intestine soon after they are taken.The author is grateful to the subjects for their continued co-operation. The dummy tablets, and the active tablets, which are available as Alka Seltzer, were kindly supplied by Miles Laboratories, Inc., Elkhart, Ind.     

Relation between gastric secretion of acid and urinary excretion of calcium after oral supplements of calcium

The object of this study was to determine in 12 healthy subjects the relation between gastric secretion of acid and absorption of calcium from two different preparations of calcium, as judged from increased outputs of calcium in the urine. The increase in urinary output of calcium after solid calcium carbonate was greater in the subjects with the most gastric secretion of acid. The absorption of calcium after a solution of monocalcium citrate was independent of gastric secretion of acid. In the four subjects with the least gastric secretion of acid, there was no absorption of calcium after calcium carbonate, but the absorption after monocalcium citrate was as great as that for those who secreted greater amounts of acid. This work was supported by a grant from Miles Laboratories, Inc., Elkhart, Indiana.     

The effects of changes in blood glucose levels on the gastric emptying rate

In this study, the gastric emptying rate has been measured in normal, peptic ulcer, and diabetic subjects, using water test meals adapted from Hunt. Glucose meals of graded concentration were also given to normal an dpeptic ulcer subjects. The zero time (fasting) blood glucose level and the level 10 min. after the start of the glucose test meals were measured and correlated with the gastric emptying rate. The gastric emptying rate has been considered in terms of its possible control by a feedback system. It has been shown, experimentally, that the blood glucose level does not, in fact, act as part of a feedback control system for the gastric emptying rate. Although the gastric emptying rate was shown to be related to the concentration of glucose and, therefore, to the osmotic pressure exerted by glucose in the test meals, theoretic considerations indicate that the braking of gastric emptying in response to a local osmotic effect would not be part of a feedback system.Supported in part by the Central Research Fund, London University, and the Royal Society.I am indebted to Professor M. D. Milne and to Dr. R. D. Tonkin for much helpful advice and for allowing me to test patients; to Drs. N. F. Coghill, R. P. K. Coe, Q. J. C. Robson, T. D. Kellock, F. Dudley Hart, and the late E. R. Cullinan, to Professor H. Ellis, and Mr. Raven for allowing me to test patients at their respective hospitals (West Middlesex Hospital, Central Middlesex Hospital, and Westminster Hospital); and to Miss P. Murray, B.Sc., and Mrs. J. Rigby, B.Sc., for technical assistance.Statistical analyses were done on an Argus computer, courtesy of Ferranti, Limited. I am grateful to Dr. P. D. Aylett for mathematical advice.Part of this work was performed during tenure of a Williams Research Fellowship, University of London.     

Effects of hydrochlorides of amino acids in test meals on gastric emptying

Four subjects were given test meals containing various concentrations of hydrochlorides of glycine, alanine, arginine, phenylalanine and tryptophan. The gastric contents were recovered after 20 min. The volume of the original meal recovered was assessed from the amount of marker substance aspirated. It was found that the slowing of gastric emptying of amino acid hydrochlorides was consistent with their action as weak acids. However, tryptophan and phenylalanine were slightly more effective than was predicted on the basis of their actions as acids.     

Lysine acetylisalicylate inhibits the protein synthesis in the rat gastric mucosa in vivo and in vitro

Lysine acetylsalicylate (LAS), a water soluble derivative of acetylsalicylic acid and parenterally administrable analgesic, locally inhibits the incorporation of 14C protein hydrolysate into proteins of the rat isolated gastric mucosa. A similar effect on protein synthesis was observed after s.c. administration of the drug, whereas DNA and RNA synthesis were not affected. Obviously, LAS inhibits the translation step during biosynthesis of proteins. It is conceivable that this effect contributes to the potential ulcerogenic action of acetylsalicylate and that parenteral administration is not a criteria to protect the stomach from salicylate-induced side effects.     

Studies of the effect of metoclopramide and apomorphine on gastric emptying and secretion in man

With oral and intravenous doses of metoclopramide there was no constant effect on the gastric emptying of test meals of glucose or sodium citrate, nor was secretion of acid by the stomach in response to test meals of glucose or sodium citrate affected. Apomorphine, in subnauseous doses (0.25 mg intravenously) slowed the gastric emptying of test meals containing sodium citrate, and 10 mg of intravenous metoclopramide abolished the slowing of gastric emptying caused by apomorphine.     

Rapid gastric emptying in duodenal ulcer patients

Isosmotic liquid peptone meals adjusted to pH 7, 3, and 1.5 were instilled on separate days into the stomachs of 8 duodenal ulcer patients and 7 healthy controls. Using a marker-dilution method, duodenal acid load (DAL) was measured as the amount of unbuffered hydrogen ions delivered to the duodenum per unit time. Gastric emptying was measured as the total volume of gastric contents, including meal plus gastric secretion, passing through the pylorus per unit time (VPP). Mean pentagastrin-stimulated acid output was not significantly different between the two groups. However, after all three test meals, mean DAL was significantly greater in duodenal ulcer than in normal subjects in both hours of the test, and VPP was significantly greater in ulcer than in normal subjects in the first 40 min. In both groups, following peptone meals of pH 7 and 3, the volume of gastric contents delivered through the pylorus decreased as the amount of free hydrogen ions entering the duodenum increased, but a given load of acid was less effective in slowing emptying in duodenal ulcer patients than in controls. These studies indicate that duodenal ulcer patients empty liquid meals more rapidly than do normal subjects, independent of the initial pH of the meals, and that, in addition, acid inhibition of gastric emptying is defective in duodenal ulcer.Dr. Grossman died May 26, 1981.S. K. Lam was a visiting scientist from the Department of Medicine, University of Hong Kong. Queen Mary Hospital, Hong Kong. M.I. Grossman holds a Veterans Administration Senior Medical Investigatorship.These studies were supported by National Institutes of Arthritis, Metabolism and Digestive Diseases grant AM 17328 to the Center for Ulcer Research and Education and by Veterans Administration Research Funds.This work was presented in part in abstract form at the 80th Annual Meeting of the American Gastroenterological Association, New Orleans, Louisiana, May 19–25, 1979.     

Aspirin and gastroduodenal toxicity. A double-blind endoscopic study of the effects of placebo, aspirin and lysine acetylsalicylate in healthy subjects

The aim of this double-blind endoscopic study was to compare the effects of placebo (group I, 5 patients), lysine acetylsalicylate (group II, 7 patients) and acetylsalicylic acid (group III, 7 patients) on the gastric and duodenal mucosa in healthy humans. Endoscopy was performed before and one hour after endoscopic instillation of aspirin (500 mg) or placebo in the stomach. Endoscopy was repeated after one week of aspirin-treatment (2 g per day) or placebo. Endoscopic findings were graded from 0 to 6 with regard to the aspect of the lesions (petechiae, erosions, ulcers) and to their number (less than 10; greater than 10). One hour after placebo instillation endoscopic findings were normal in all the patients of group I. Three and 5 patients of groups II and III, respectively, developed gastric lesions but none had duodenal lesions. At day 8 only one subject from group I had gastric petechiae. After one week of aspirin-treatment, 13 out of the 14 subjects of groups II and III developed gastric lesions and 3 in each group had duodenal lesions. The endoscopic score was significantly higher in group III than in group II for the following localisations: fundus, antrum, entire stomach, and stomach + duodenum. However the duodenal score was not significantly different between these 2 groups. It is concluded that, after a one-week treatment in normal patients, standard aspirin produces 2 fold more gastric mucosal damage than does soluble aspirin.     

Effect of various test meals on gastric and jejunal carbon dioxide: A study in healthy subjects

OBJECTIVE: The normal pattern of carbon dioxide (CO2) levels in the human stomach and small bowel after meals is unknown. The intraluminal carbon dioxide level is a sensitive and early marker for organ mucosal ischemia. CO2 levels in both the stomach and small bowel are influenced by multiple factors other than adequacy of perfusion. Gastric acid production, salivary bicarbonate and CO2 produced or absorbed by meals are the disturbing variables. Prolonged gastric (and jejunal) tonometry after meals can be of additional value in the work-up of patients suspected of (chronic) gastrointestinal ischemia. The purpose of this study was to challenge these problems using in vitro tested meals and a rigid acid-suppression regimen in a group of healthy subjects. MATERIAL AND METHODS: Standard meals were tested in vitro on the ability to produce and buffer CO2. Meals with the least CO2 variations were subsequently used in healthy subjects. Tonometry of the stomach and jejunum was performed for 24 h, with optimal and controlled acid suppression. RESULTS: Ten subjects were enrolled in the study. Acid production was sufficiently suppressed. The gastric PCO2 baseline (fasting) was 6.5 (1.0), and significantly lower than the jejunum PCO2 baseline of 7.6 (0.9) kPa. The gastric baseline during the day was 6.9 (1.6), and significantly lower than the gastric baseline during the night of 8.0 (1.8), suggesting a diurnal variation of PCO2. Increases in PCO2 levels were seen in all subjects, after meals and between meals. CONCLUSIONS: Prolonged gastric and jejunal tonometry is feasible in humans. PCO2 levels were seen to peak after, but also in-between, most meals. The diurnal variation in PCO2 might reflect reversible gastric mucosal ischemia.     

Placement of the Bravo wireless pH monitoring capsule onto the gastric wall under endoscopic guidance

BACKGROUND: The Bravo system was designed mainly to monitor esophageal pH, and there have been no reports on gastric pH monitoring using this system. OBJECTIVE: To place the Bravo capsule on the gastric wall and monitor gastric pH. DESIGN: Experimental clinical trial with the cooperation of volunteers. SETTING: Academic medical center. PATIENTS: Eleven volunteers (9 men, 2 women; mean age 38 years; 3 had symptoms of GERD). INTERVENTIONS: The Bravo system was introduced into the esophagus and stomach along a thin endoscope and capsules were attached, one each to the esophageal and gastric walls under direct vision through the endoscope. Esophageal and gastric pHs were simultaneously monitored. RESULTS: The 2 capsules were successfully placed in 10 of the 11 subjects, and both esophageal and gastric pHs were monitored for 48 hours in 9 subjects. Mild to moderate precordial pain was observed in 7 subjects, but no other complications or side effects were observed in this study. The gastric pH of 10 subjects increased after meals and returned to baseline pH 2 hours later. Decrease of esophageal pH was observed 1 hour after a meal in the symptomatic subjects and corresponded to the time when gastric pH decreased secondary to the increase of pH with meals. CONCLUSIONS: The Bravo capsule is easily placed on the gastric wall under endoscopic assistance and enables long ambulatory monitoring of gastric pH.     

The effects of glucagon and glucose on the human stomach

Conclusions Glucagon given by continuous intravenous infusion consistently decreases the gastric acid and pepsin output of human subjects for several hours. Ten per cent glucose produces varying depressions in gastric acid and pepsin output. In humans, glucose and glucagon together act consistently to raise the gastricpH and to lower the gastric pepsin concentration throughout the period of administration.Aided in part by grants C-2578 and A-1785 from the U. S. Public Health Service.We are grateful to Mrs. Julia Zalokar, of the Bio-Statistics Department, for her evaluation from a statistical standpoint of this material; and to Mr. Joseph Coscia, Mrs. Nancy Iannotti, Mrs. Felicia Mestel, and Miss Bea Pask, for their technical assistance.Crystalline glucagon, Lot #0358-PA-60923, AX 29821, was kindly supplied by Dr. Glenn W. Irwin, of Lilly Laboratories.     

Gastrointestinal function in obesity: motility, secretion, and absorption following a liquid test meal.

Digestive responses to a 300-mL liquid fat-rich meal (432 kcal) in a group of massively obese patients were compared with those observed in a group of healthy lean subjects of variable body weight. Gastric and intestinal propulsion, digestive secretions, and absorption in the proximal 70 cm of intestine were measured using a multiple-marker dilution method. The average gastric emptying of energy, acid, volumes, and meal marker were similar in the two groups 80 minutes after intake, justifying a comparison of intestinal processing of the meal. Compared with lean subjects, the obese subjects responded with less pancreatic secretion (P less than .05) and gallbladder emptying, but absorbed a larger proportion of the emptied energy in the test segment (P less than .01) during a similar or shorter transit time. In addition, when the entire meals were compared, the obese group generally absorbed the test meal more effectively and rapidly in the upper part of the intestine. As a consequence, the flow volumes at the exit of the test segment were lower (P less than .05), and less of the test meal was propulsed to distal parts of the intestine. In the lean subjects, the body weight or height correlated positively with the gastric emptying rate, peak gastric acid output, and pancreatic responses, and negatively with (P less than .05) the segment transit time. The taller the subject, the greater the proportion of the meal which was rapidly propulsed unabsorbed to lower parts of the intestine, indicating that a large intestinal area was exposed for rapid energy uptake. No such correlations were observed in the obese group.     

The effect of acute hyperglycemia on meal-stimulated gastric, biliary, and pancreatic secretion, and serum gastrin.

The effects of hyperglycemia on pancreatic, biliary, and gastric secretory responses to meals have not been hitherto quantified in man. In the present study seven normal volunteers were fed on two occasions a 500-ml liquid test meal containing fat and protein. During one of the meals the subjects were made acutely hyperglycemic with intravenous glucose, whereas in control experiments, each subject received intravenous saline in place of glucose. A jejunal perfusion method was used to measure pancreatic outputs of trypsin and biliary outputs of bile salts for 150 min after the meal; the same method was used to quantify indirectly the amount of acid secreted by the stomach in the 150-min period. Serum gastrins were also measured basally and at intervals after the meal. Hyperglycemia suppressed serum gastrin, gastric acid production, trypsin secretion, and bile salt output in response to the test meal.     

Changes in gastric environment with test meals affect the performance of 14C-urea breath test

BACKGROUND: (14)C-urea breath test (UBT) is considered to be an accurate diagnostic test for the detection of active Helicobacter pylori infection. Various test meals are used in (14)C-UBT to slow down gastric emptying, and to enhance the gastric distribution, in order to increase the time and area of contact between microorganisms and the tracer substrate. The aim of the present paper was to evaluate the effect of gastric environment on the performance of (14)C-UBT using an alkaline and an acidic liquid test meal having gastric emptying retardant effect. METHODS: The comparison of (14)C-UBT was done with liquid test meals (200 mL water) comprising (i) plain drinking water (PDW); (ii) 1.3 g or 3.0 g citric acid (CA); and (iii) 3.0 g trisodium citrate (TSC). Eighteen patients (37 +/- 12 years, range 18-57 years) with complaints of dyspepsia participated in the study. The status of H. pylori was confirmed by histology and rapid urease test. A total of 93 kBq of (14)C-urea (0.5 mL) in a gelatin capsule was orally administered along with liquid test meals to the overnight fasting subjects. Breath samples were collected and radioactivity measured. Results were expressed as (14)CO(2)/mmol exhaled CO(2) as percentage of administered radioactive urea. RESULTS: Higher acidic gastric environment (pH approx. 2.0) with CA was found to increase the exhaled (14)CO(2) level in a dose-dependent manner as compared to PDW and TSC meal (P < 0.05) at all time points. With TSC test meal, the expired (14)CO(2) level decreased in the lower acidic gastric environment (pH approx. 5.3). The peaks of exhaled (14)CO(2) with TSC test meal were observed at the same time points as that with PDW and CA test meals. The (14)C-UBT with TSC was found to be positive in 77% of patients (10/13). CONCLUSION: Better interaction between the microbial urease and (14)C-urea, caused by a test meal that retards gastric emptying and that changes gastric pH, plays an important role in hydrolysis of the administered (14)C-urea by H. pylori urease.     

Citric acid as the test meal for the 13C-urea breath test

OBJECTIVE: Test meals are used in the urea breath test to slow gastric emptying and to increase the area of contact with the substrate. Recently, citric acid has been suggested as an improved liquid test meal. The mechanism is unknown and could act by delaying gastric emptying, decreasing the pH at the site of the bacteria, or both. Our aim was to evaluate the effects of citric acid test meals on urea hydrolysis in vivo, to identify the possible mechanism for enhanced urea hydrolysis, and to identify the minimum effective dose. METHODS: We compared the U.S. commercial 13C-urea breath test with four liquid test meals (200 ml of water) consisting of citric acid, ascorbic acid, sodium citrate, and glucose polymer and also after the subcutaneous administration of pentagastrin. We studied healthy volunteers with and without proven H. pylori infection (by serology and histology). 13C-urea was administered orally simultaneously with the liquid test meals or immediately after the pudding had been ingested. Breath samples were taken before and after oral administration of the 13C-urea. RESULTS: A dose response in urease activity was evident as the amount of citric acid was increased from 1 to 4 g. Citric acid at 1, 2, or 4 g produced significant increases in breath 13CO2 activity, compared with the commercial pudding (p < 0.05). Ascorbic acid (p = 0.053), subcutaneous pentagastrin (to lower pH) (p = 0.199), and glucose polymer (p = 0.03) (to delay gastric emptying) all approximately doubled breath 13CO2, compared with the commercial kit. Nevertheless, the increases were all significantly less than with the 4 g citric acid test meal. CONCLUSIONS: The data are consistent with the marked effect of citric acid on gastric emptying and, possibly, distribution of the urea within the stomach being largely responsible for the enhanced urease activity with citric acid test meals. It should be possible to use a low dose of citric acid (e.g., 1 g per 200 ml) to enhance the simplicity and palatability of the test.     

Ileal lesions in Behçet's disease originate in Peyer's patches: Findings on magnifying endoscopy

The possible influence of moderate amounts of acetylsalicylic acid (ASA) on gastric emptying, duodeno-gastric reflux and small bowel propulsion was studied in rats with permanent gastric and duodenal tubes. The ASA-containing or the control solution was introduced intra-gastrically half an hour before the simultaneous administration of differently labelled radioactive test meals into the stomach and the duodenum. ASA was given as 7.5 or 15.0 mM solution in 100 mM hydrochloric acid or in 100 mM sodium chloride. After 15 minutes the gastrointestinal propulsion was examined. No effect of the ASA treatment was noted. No increase in duodeno-gastric reflux was found in the ASA-treated animals.     

Gastric acid secretory differences in patients with Heineke-Mikulicz and Finney pyloroplasties

To study gastric emptying and secretion, liquid meals of 10% glucose lasting 15 and 30 min, and physiological saline meals lasting 30 min, all containing phenol red as a gastric nonabsorbable marker, were given to postvagotomy patients with Finney or Heineke-Mikulicz pyloroplasties. No differences in emptying were found. A small but statistically greater amount of acid was found in the stomach with the 15-min glucose meal after Heineke-Mikulicz pyloroplasty. This represented greater acid secretion into glucose meals generally after Heineke-Mikulicz pyloroplasties, because of the larger volume contained in the stomach at 15 min. 15-min glucose meal acid secretion correlated with basal acid concentration but not with insulin-stimulated gastric acid output. The small excess of acid in the Heineke-Mikulicz group's 15-min glucose meals may represent a small, maintained excess of gastric acid in this group detected only in the brief glucose meals due to rapid and erratic gastric emptying of liquids after vagotomy.