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Effect of food on gastrointestinal transit of liquids in cynomolgus monkeys.

We investigated the gastrointestinal transit of liquids, as well as various gastric pH profiles, in fed cynomolgus monkeys. Twelve grams of a biscuit-type solid food were provided 1 h before the test. The acetaminophen method was used to determine the gastric half-emptying time (t(50%)), which provided an estimate of the gastric emptying rate. The gastric emptying rate of liquids was significantly reduced after food intake in monkeys. The mean t(50%) value was 143.5 min and comparable to that of humans after eating. However, there was a large variability in the t(50%) between individual animals as shown by the coefficient of variance of approximately 80%. Next, the median oro-caecal transit time in fed monkeys was determined to be 1.8 h, using the sulfasalazine-sulfapyridine method. There was no significant difference in oro-caecal transit time between unfed and fed monkeys; thus, food intake has no significant effect on the oro-caecal transit time of liquids in either monkeys or humans. However, the oro-caecal transit time in humans is about 2 h longer than that in monkeys. Our experiments using several different foods suggested that the typical human gastric pH profile could not be simulated in fed monkeys.

Acetaminophen↗

Gastric mucosal protection from enteral nutrients: role of motility.

BACKGROUND: Cold restraint stress increases the force of gastric contractions and produces gastric mucosal injury in rats. The aim of our study was to determine whether enteral glucose or hyperglycemia alone would alter the stress-induced gastric motility pattern and ameliorate the associated gastric mucosal injury. METHODS: Adult male rats underwent surgical placement of gastric catheters, jugular venous catheters, and gastric strain gauge transducers 5 days before cold restraint. Three groups of rats received different substances during the same cold restraint stress protocol. Group 1 received 0.9% NaCl, 2 mL/h infused both intravenously (i.v.) and intragastrically (i.g.); group 2 received 0.9% NaCl, 2 mL/h i.g. plus 25% glucose, 2 mL/h i.v.; and group 3 received 0.9% NaCl, 2 mL/h i.v. plus 25% glucose i.g. Following baseline gastric motility measurements, all rats were restrained for 2 hours at 20 degrees C followed by 2 hours at 4 degrees C. RESULTS: Restraint even at room temperature increased the force of gastric contractions; the cold environment gradually prolonged gastric contractions. Enteral glucose blunted the effects of stress on gastric motility, increased gastric residual volume, decreased gastric acidity, and prevented gastric mucosal injury. Parenteral glucose had little effect on any gastric parameters. CONCLUSIONS: Enteral glucose prevents the abnormal gastric motility pattern that is necessary to produce the gastric mucosal injury associated with cold restraint stress, but hyperglycemia alone has little effect on the pathophysiology of cold restraint.

Animals↗

Diet and chronic atrophic gastritis: a case-control study.

A hospital-based case-control study of gastric cancer precursor lesions was conducted in a high-risk black population in southern Louisiana. Ninety-three subjects with biopsy-proved advanced chronic atrophic gastritis were compared to two control series: a gastroscopy clinic series and a general hospital-admission series. Dietary case-control differences indicated a protective effect associated with fruit and vegetable intake and with dietary vitamin C and a risk elevation associated with milk consumption. The protective effect associated with consumption of fruits, vegetables, and vitamin C is consistent with findings for gastric cancer and with the etiologic hypothesis of intragastric nitrosation. A twofold increased risk was associated with cigarette smoking. Gastric juice pH, NO3-, and NO2- were determined for subjects undergoing gastroscopy, and comparisons were made between this high-risk U.S. group and a Colombian population with a much greater magnitude of risk; the latter had higher NO3- and NO2- levels. An increase in pH was associated with increasing severity of gastric lesions. Levels of pH and NO2- concentration were significantly correlated (P less than .0005); however, in Louisiana the large difference in NO2- concentration associated with pH elevation is not associated with histopathologic severity. Divergent trends with severity of lesions for NO3- concentration were seen in the two populations.

Adult↗

Gastric volume and pH in out-patients.

We measured the volume and pH of the gastric content of 21 out-patients and 21 in-patients under general anaesthesia. Gastric tubes were inserted after induction of anaesthesia, and gastric fluids were withdrawn for pH determinations. Gastric volumes were measured by a dilution technique using polyethylene glycol as the indicator and also by measurement of the volume aspirated through a gastrict tube. Out-patients had a mean gastric volume of 69 +/- 17 ml while in-patients had a mean volume of 33 +/- 4 ml. The average gastric pH for the out-patients was 1.8 +/- 0.2 and for the in-patients 2.0 +/- 0.3. Four out-patients had more than 75 ml of gastric fluid of pH less than 2.0. Aspiration through a gastrict tube did not empty the stomach completely and the volume thus obtained gave a falsely low estimate of the gastric volume.

Adult↗

Effect of sucralfate on gastric intramucosal pH in critically ill patients.

OBJECTIVE: To determine whether sucralfate administration affects the tonometric measurement of gastric intramucosal pH (pHi). DESIGN: Non-randomized observational study. SETTING: General intensive care unit of a teaching hospital. PATIENTS: Twenty critically ill, mechanically ventilated, consecutively admitted patients requiring an arterial catheter and nasogastric tube. INTERVENTIONS: Tonometer placement and sucralfate administration. MEASUREMENTS AND MAIN RESULTS: We simultaneously determined tonometer saline PCO2 (PCO2i), arterial blood gases, pH of gastric juice and pHi. These parameters were evaluated immediately before sucralfate administration, and 2 h and 4 h after. We did not detect any change in either PCO2i or pHi after sucralfate administration (PCO2i: basal 6.4 +/- 1.7, 2 h 6.3 +/- 1.7, 4 h 6.3 +/- 1.7; pHi: basal 7.35 +/- 0.13, 2 h 7.36 +/- 0.12, 4 h 7.36 +/- 0.12). CONCLUSIONS: Sucralfate does not affect the tonometric measurement of PCO2i and pHi.

Adult↗

Effectiveness of pH measurements in predicting feeding tube placement: an update.

This paper reports further findings from an ongoing clinical study designed to evaluate the extent to which pH values of aspirates from feeding tubes can be used to differentiate between gastric and intestinal tube placement and gastric and respiratory tube placement. The sample consisted of 405 aspirates from small-bore nasogastric tubes and 389 aspirates from nasointestinal tubes, which were obtained from 605 subjects ranging in age from 18 to 94 years. Data were collected at the time of initial placement and again, when possible, after feedings were initiated. A total of 794 pH-meter readings were made concurrently with X-rays to determine feeding tube position. Gastric placement was successfully distinguished from intestinal placement of the feeding tubes on the basis of pH-meter readings (p < .0001). Approximately 85% of the 405 pH-meter readings from gastric fluid were between 0 and 6.0, while over 87% of the 389 pH-meter measurements performed on intestinal aspirates were greater than 6.0. Four aspirates from feeding tubes inadvertently placed in the respiratory tract (two in the pleural space and two in the tracheobronchial tree) were tested with a pH-meter, all had pH values greater than 6.5.

Adolescent↗

Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats.

BACKGROUND & AIMS: The trefoil factors, a family of proteins abundantly expressed in gastrointestinal mucous cells, protect the epithelium in vitro. This study determines the effects of exogenously administered trefoil peptides on experimental injury in rats in vivo. METHODS: Gastric injury was induced by either intragastric absolute ethanol (1.0 mL) or subcutaneous indomethacin (20 mg/kg). Recombinant human spasmolytic polypeptide (rHSP) or rat intestinal trefoil factor (ITF) were administered at different doses and time points before or after injury. Vehicle or bovine serum albumin was used as control. The pH of the stomach contents was assessed when the rats were killed. Gastric injury was blindly evaluated macroscopically and histologically. Serum levels of rHSP and ITF were determined by an enzyme-linked immunosorbent assay. RESULTS: Oral rHSP and ITF markedly protected against both ethanol- and indomethacin-induced gastric injury (P < 0.005 at doses of 1-15 mg/rat) when given up to 2 hours before injury; no protection was noted by intraperitoneal rHSP against ethanol injury. Intraperitoneal rHSP protected against indomethacin-induced injury only at the maximal dose given (15 mg). Neither rHSP nor ITF altered gastric pH. Protection was not associated with systemic absorption of trefoil peptides. CONCLUSIONS: Topical trefoil peptides protect the gastric mucosa against ethanol- and indomethacin-induced gastric injuries. These peptides contribute to surface mucosal defense.

Administration, Oral↗

The effect of metoclopramide on gastric contents after preoperative ingestion of sodium citrate.

Because sodium citrate is known to increase both gastric pH and gastric volume while metoclopramide decreases gastric volume, we evaluated, in a double-blind randomized study, the effect of combining metoclopramide with sodium citrate on gastric pH and volume after induction of anesthesia in 60 female patients to determine whether gastric pH could be increased at the same time that gastric volume was decreased. All patients received 50-ml sodium citrate. To mimic standard anesthetic practice, all patients were premedicated: 20 patients received meperidine alone, 20 received meperidine plus 20-mg metoclopramide, and 20 received diazepam plus 20-mg metoclopramide. Metoclopramide failed to decrease median gastric volume or to increase the number of patients with gastric volumes less than 25 ml. There was no difference in median pH values in the three groups of patients. In patients receiving metoclopramide, the risk of pH values less than 2.5 was greater with gastric volumes less than 25 ml than in patients with volumes greater than or equal to 25 ml. We conclude that preoperative metoclopramide does not decrease gastric volume in patients premedicated with meperidine or diazepam and that when gastric volume was less than 25 ml the neutralizing effect of sodium citrate was lost.

Adult↗

Effect of the somatostatin analogue octreotide on gastric fluid pH in ponies.

The effect of the somatostatin analogue, octreotide, on gastric fluid pH was investigated in 4 ponies. Gastric fluid pH was determined after SC administration of octreotide or physiologic saline solution (control). A baseline sample of fluid was obtained, the agent was given, and 8 additional samples were collected hourly. Administration of octreotide at all dosages tested (0.1, 0.5, 1.0, and 5.0 micrograms/kg of body weight) increased gastric pH to > 5.0. Baseline values were consistently < 2.7. Administration of octreotide at these same dosages induced gastric pH values > 4.0 for 2.4 +/- 1.2, 4.8 +/- 0.8, 5.7 +/- 1.3, and 5.4 +/- 2.6 (mean +/- SD) continuous hours, respectively. Treatment at all dosages increased the pH of gastric fluid, compared with control values. The duration of the increase in pH was significantly (P < 0.05) different than that of the control treatment, even for the lowest dosage, 0.1 microgram/kg.

Animals↗

An evaluation with piglets of bovine milk, hydrolyzed bovine milk, and isolated soybean proteins included in infant milk formulas. II. Stomach-emptying rate and the postprandial change in gastric pH and milk-clotting enzyme activity.

The piglet was used as a model for the human infant to determine the effect of the protein source of a milk formula on stomach-emptying rate and the postprandial changes in gastric pH and milk-clotting enzyme activity. Three liquid milk formulas containing either intact bovine milk protein, hydrolyzed bovine milk protein, or isolated soybean protein as the sole source of dietary protein were given to five 37-day-old piglets that had undergone surgery for the preparation of a simple gastric fistula. At set times after commencement of a meal, the stomach contents were removed via a gastric cannula and weighed; then pH and milk-clotting enzyme activity were determined. The isolated soybean protein-based formula tended to empty from the stomach more slowly than did the bovine milk-based formulas. Maximum difference (p less than 0.05) was found at 3 h postfeeding, where 30% of the ingested soybean formula dry matter remained in the stomach; comparable values for the intact bovine milk-based formula and hydrolysate were 22 and 12%, respectively. The type of protein did not significantly (p greater than 0.05) affect the postprandial change in gastric pH or gastric milk-clotting enzyme activity. Gastric pH increased sharply after feeding, from pH 1.5 at 0 h to pH 5.2 at 1 h, and then fell gradually over the following 4 h to pH 1.84.

Analysis of Variance↗

Effect of nasogastric suction and ranitidine on the calculated gastric intramucosal pH.

OBJECTIVE: To study the effect of nasogastric suction and ranitidine on the determination of gastric intramucosal pH (pHi). DESIGN: Prospective study. SETTING: Clinical research unit at a university hospital intensive care department. SUBJECTS: 12 healthy volunteers. INTERVENTIONS: After a 2-h measurement control period a tonometer was connected to nasogastric suction for 2 h, and thereafter ranitidine was given intravenously and gastric pHi measured. MEASUREMENTS AND RESULTS: During each 2-h measurement period gastric PCO2, gastric pHi, and pH gap were determined every 30 min. Luminal pH was measured after insertion of tonometer and at the end of each study period. Neither nasogastric suction nor ranitidine had an effect on the coefficient of variation for either gastric PCO2 or pHi. Compared to control and nasogastric suction periods, after ranitidine mean gastric pHi was higher (control 7.22 +/- 0.08; nasogastric suction 7.23 +/- 0.07; after ranitidine 7.31 +/- 0.06, p < 0.001) mean gastric PCO2 lower (control 6.4 +/- 1.3; nasogastric suction 6.5 +/- 1.3; after ranitidine 5.3 +/- 0.9, p < 0.001) and pH gap lower (control 0.18 +/- 0.08; nasogastric suction 0.17 +/- 0.05; after ranitidine 0.09 +/- 0.06, p < 0.01). Luminal pH increased after ranitidine in each subject. CONCLUSIONS: H2 blockers have no effect on the reproducibility of gastric pHi measurements, but the use of H2 blockers modifies the normal values for gastric pHi in healthy subjects.

Adult↗

Physiologic considerations in drug absorption from the gastrointestinal tract.

The dynamic interaction between variables within the gastrointestinal tract and the physiochemical properties of a drug in a delivery system determine the rate and extent of absorption of that drug. Among the major physiologic variables are pH, gastric emptying time, and intestinal transit time. Some physicochemical properties of interest include solubility, particle size, and chemical form of the drug. Attributes of the formulation such as controlled-release mechanism, pH sensitivity, and size, shape, and density of the product can also affect absorption. Food has also been reported to influence the absorption from some but not all controlled-release products. As a more thorough understanding of the many factors involved in drug absorption is developed, the formulation of more sophisticated oral drug delivery systems will be possible.

Chemistry, Pharmaceutical↗

Mechanisms for nitrite loss from the stomach.

Nitrite loss from the stomach was studied using dogs equipped with Thomas cannulas for direct access to the stomach lumen. Solutions containing sodium nitrite and non-absorbable volume marker (polyethylene glycol, PEG) were infused into the stomach, and samples were taken over 60 min to determine the concentration of 'total nitrite' (including NO2-, HNO2 and other species in equilibrium with NO2-) and rate of dilution of the stomach contents as a function of time. Changes in stomach volume were also measured. Nitrite loss was found to be very rapid, with total nitrite concentrations declining to less than half the initial levels in 10 min. The decay in total nitrite concentrations was due predominantly to gastric absorption, with small additional contributions from dilution of the stomach contents (inferred from PEG concentrations) and chemical reactions (from in vitro kinetic data). Results for initial nitrite concentrations varying over a range of 0.15-4.5 mM showed absorption to be first order in total nitrite. The permeability-area product for nitrite absorption (PA) was about 0.6 l/h, and was unaffected by the addition of 1 mM SCN- or Cl-. All of these results are consistent with nitrite absorption in the form of NO2- or HNO2. Buffering the infusate with HCO3- to increase luminal pH from approximately 2 to 7 caused a three-fold reduction in the apparent value of PA. When pentagastrin was used to stimulate acid secretion, nitrite absorption was only half as fast as when acid secretion was inhibited with cimetidine, or when no drug was given. This effect could not be explained by variations in luminal pH, and suggests that acid secretion either decreases PA or is accompanied by active secretion of nitrite. Based on these data, a mathematical model was developed to stimulate the physical and chemical factors governing nitrite concentrations in the stomach.

Animals↗

Gastric intramucosal pH and hepatic venous oximetry after cardiopulmonary bypass in valve replacement patients.

To determine splanchnic perfusion after cardiopulmonary bypass, gastric intramucosal pH (pH(i)) and hepatic venous oxygen saturation (SHVO2) were measured in 14 patients with cardiac valve replacement. Blood samples were analysed at 6, 12 and 24 h after admission to an intensive care unit. Gastric pH(i) increased significantly (P < 0.01) from 7.21 at 6 h to 7.31 at 12h and increased to 7.37 at 24 h while SHVO2 increased significantly (P < 0.05) from 48% at 6 h to 57% at 12 h and 24 h. Cardiac index was > 4 l/min per m2 and mixed venous oxygen saturation > 70%. Despite sufficient cardiac output, splanchnic perfusion decreased after cardiopulmonary bypass and recovered within 24 h after admission to the intensive care unit. It is concluded that gastric pH(i) and SHVO2 are useful parameters for monitoring postoperative splanchnic perfusion in patients with open-heart surgery.

Acid-Base Equilibrium↗

Development of an in vitro system simulating bucco-gastric digestion to assess the physical and chemical changes of food.

The release of nutrients from solid food depends on the physical and chemical characteristics of substrates, and on dynamic physiological events including pH, gastric emptying and enzymatic secretion. Our laboratory has developed an in vitro digestive system mimicking mouth and stomach processes to determine physical and chemical changes of bread during digestion. To simulate oral-phase digestion, bread was minced and subjected to in vitro amylase digestion, releasing 219 +/- 11 g oligosaccharides/kg total carbohydrate. During the gastric phase, bread proteins, which are converted into insoluble aggregated proteins during breadmaking, were emptied in various states of peptic digestion: undigested aggregated proteins and degraded proteins of intermediate and low molecular weight. The mean particle size of ground bread decreased progressively to the end of the gastric digestion (from 292 to 109 microm). The in vitro digestive system proved to be a useful tool for understanding the dynamic digestion of various food components held within the structure of a food matrix.

Bread↗

Helicobacter mustelae-induced gastritis and elevated gastric pH in the ferret (Mustela putorius furo).

Helicobacter mustelae has been cultured from the stomachs of ferrets with chronic gastritis; the lesions in the stomach have many of the same histological features seen in H. pylori gastritis in humans. To determine whether H. mustelae-negative ferrets with normal gastric mucosa were susceptible to colonization and whether gastritis developed after infection, four H. mustelae-negative ferrets treated with cimetidine were inoculated orally on two successive days with 3 ml (1.5 x 10(8) CFU) of H. mustelae; eight age-matched H. mustelae-negative ferrets served as controls. All four ferrets became colonized; H. mustelae persisted through week 24 of the study, as determined by positive gastric culture, tissue urease, and Warthin-Starry staining of gastric tissue. Superficial gastritis developed in the oxyntic gastric mucosa, and a full-thickness gastritis, composed primarily of lymphocytes and plasma cells plus small numbers of neutrophils and eosinophils, was present in the antrum. The inflammation was accompanied by an elevation of immunoglobulin G antibody to H. mustelae. At 4 weeks post-inoculation, the four infected (experimental) ferrets developed an elevated gastric pH (4.0 to 5.2) for 2 weeks. The eight control ferrets did not have gastritis; H. mustelae could not be demonstrated in gastric tissue via culture, nor was there an immune response to the bacteria. In ferrets, H. mustelae readily colonizes the stomach and produces a gastritis, a significant immune response, and, like H. pylori infection in humans, a transient elevated gastric pH after Helicobacter infection.

Animals↗

Effect of ranitidine on intragastric pH in clinically normal neonatal foals.

OBJECTIVE: To determine intragastric pH in newborn foals and to examine the effect of i.v. or oral administration of an H2-receptor antagonist on intragastric pH. DESIGN: Prospective controlled study. ANIMALS: 6 healthy mixed-breed neonatal foals. PROCEDURE: Intragastric pH was measured, using an antimony electrode. Foals were monitored on days 2, 4, and 6 after birth, and each received 3 treatments. The pH was recorded for 4 hours before treatment and for 10 hours after ranitidine administration (2 mg/kg [0.91 mg/lb] of body weight, i.v.; 6.6 mg/kg [3 mg/lb], PO) or 20 hours after corn syrup administration. Mean and median pH and percentage of time pH was > or = 4 were calculated. RESULTS: Mean intragastric pH significantly increased for 5 hours after i.v. administration of ranitidine, compared with baseline data. Percentage of time intragastric pH was > or = 4 increased significantly for 4 hours after ranitidine administration, and median pH increased significantly for hours 2 to 4 after administration. Oral administration of ranitidine significantly increased mean and median pH for hours 2 to 8 after administration and percentage of time pH was > or = 4 for hours 2 to 7 after administration. CLINICAL IMPLICATIONS: Neonatal foals have highly acidic gastric fluid. Intravenous or oral administration of ranitidine significantly increased intragastric pH for 4 and 8 hours, respectively. Suckling affected intragastric pH and underscored the need for frequent feeding of neonatal foals.

Administration, Oral↗

Sodium citrate in paediatric outpatients.

To determine whether the gastric content pH of paediatric patients could be raised in an effort to decrease post-aspiration morbidity and mortality, the antacid sodium citrate (0.4 ml.kg-1) was given preoperatively to 25 patients aged 1 to 14 (6.0 +/- 3.5, mean +/- SD) years. Their gastric content pH was measured following induction of anaesthesia. These values were compared to those obtained from a control group (n = 20) ranging in age from seven months to nine (3.3 +/- 2.7) years. A gastric content pH value of greater than 2.5 was measured in 23 of the 25 patients who received sodium citrate. There were only two patients in the control group with a gastric content pH greater than 2.5, p less than 0.001, Fisher exact test. Only one child refused to take the medication. The administration of sodium citrate appears to be an effective method of raising the gastric content pH in paediatric patients.

Ambulatory Care↗