Is plasma GABA of peripheral origin?

Plasma levels of gamma-aminobutyric acid (GABA) appear to be altered in affective disorders and alcoholism. Plasma levels of GABA were not affected by menstrual cycle, exercise, gender, gut flora, nor by cholinergic stimulation by bethanechol. An obvious peripheral source for plasma GABA could not be demonstrated.

Biliary excretion of intravenous [14C] omeprazole in humans.

We have studied the biliary excretion of [14C] omeprazole in humans. The study was performed in eight healthy subjects and the technique used was based on multiple marker dilution principles with double-lumen tubes placed in both the stomach and intestine. The results obtained show a 16% biliary excretion of [14C] omeprazole. These data suggest a minimal "spillover" of omeprazole from the gastric mucosa into the gastric lumen in humans. The results also agree with previous data of the fecal recovery of radiolabeled omeprazole that suggest that the fecal excretion of intravenous omeprazole in humans is entirely accounted for by biliary excretion.

High-fiber diets: influence on characteristics of cecal digesta including short-chain fatty acid concentrations and pH.

The effects of two sources of dietary fiber on the characteristics of cecal contents were assessed directly with miniature swine cannulated to facilitate frequent collections of cecal digesta. The short-chain fatty acid (SCFA) concentrations increased and the pH decreased at the same time that meal constituents entered the cecum; PEG was used as a dietary marker. The bean diet resulted in higher concentrations of acetate and total SCFA in cecal digesta, lower concentrations of butyrate, a larger SCFA pool size, and a more acidic pH than did the bran diet. Thus, we conclude that SCFA concentrations and acidity of the digesta are directly related and that dietary fibers can affect simultaneously several variables that are implicated as factors influencing colonic health.

Serum immunoreactive pancreatic lipase and cationic trypsinogen for the assessment of exocrine pancreatic function in older patients with cystic fibrosis.

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P less than .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of luminal contents on postresectional longitudinal and mucosal growth in the ileum of suckling rats.

Effects of luminal contents on adaptive growth of the ileum in the neonatal small bowel of rats were examined after resection of the proximal small bowel and after removal of the ileum from the enteric stream. Four weeks after resection of the proximal 60% of the small bowel in 10-day-old rats, the distal 40% of the small bowel elongated by 281%. This distal segment also elongated by 265% after intestinal transection (p greater than 0.05), but by only 191% when it was bypassed (bypass versus resection or transection, p less than 0.001). After resection the distal villi were 81% taller, but after transection they were only 19% taller (p less than 0.001 versus resection); after bypass they did not grow (p less than 0.001 versus resection or transection). The distal crypts were 404% deeper after resection, 331% deeper after transection (p less than 0.05), and 291% deeper after bypass (p less than 0.001 versus resection, p greater than 0.05 versus transection). The DNA content was 517% greater after resection, 364% greater after transection (p less than 0.001), and 73% greater after bypass (p less than 0.001 versus transection or resection). Maximal elongation of the small bowel occurs in the presence of luminal nutrition. Increasing luminal nutrition is associated with increasing mucosal hyperplasia.

Evaluation of end-point titration, single dilution and capture enzyme immunoassays for measurement of antirotaviral IgA and IgM in infantile secretions and serum.

In order to facilitate measurement of antirotaviral IgA in large collections of faeces and secretions, adaptations of enzyme immunoassay methods for estimating antirotaviral IgA and IgM in duodenal fluid, saliva, faeces and serum were studied. To quantitate specific IgA, a single dilution of each sample was assayed. Results were expressed as antirotaviral IgA units derived from a standard curve. Units were calculated by log-logit analysis on computer. There was strong correlation between antirotaviral IgA units and end-point titres in 257 faecal samples (correlation coefficient r = 0.92) and in 182 duodenal fluids and salivary samples (correlation coefficient r = 0.74). The assay was validated using acute and convalescent faeces from children with or without rotavirus infection. Immune conversions in IgA were detected in 33 (75%) of the children by units and 34 (77%) by titres. None of nine children with gastroenteritis due to other infectious agents showed immune conversions to rotavirus. A monoclonal capture IgM assay showed similar end-point titres and numbers of immune conversions when compared with a direct assay for antirotaviral IgM in serum and secretions. Use of the capture method eliminated false-positive reactions with the cell control. The assay for antirotaviral IgA units in secretions is simple, rapid, reproducible and reliable, and has proven of value in longitudinal epidemiological studies of rotavirus coproIgA profiles. Both the capture IgM technique and the single dilution IgA method permit analysis of large numbers of specimens and are appropriate for examination of immune responses to natural rotavirus infection or during vaccine trials.

Role of parotid amylase in starch digestion in the gastro-intestinal tracts of diabetic rats.

In order for the role of parotid amylase in starch digestion in the gastro-intestinal tracts of diabetic rats to be clarified, this study investigated the effect of parotid-duct ligation on both amylase secretion from the parotid glands and pancreas into the gastro-intestinal tract and on starch digestion in the gastro-intestinal contents during feedings. In both diabetic rats and control rats, parotid-duct ligation reduced amylase activity in both the parotid glands during fasting and in the gastric contents after feeding. The amylase activity in the intestinal contents after feeding was reduced by parotid-duct ligation in the diabetic rats. Starch digestion in the gastro-intestinal tract after feeding was reduced by parotid-duct ligation in the diabetic rats. The results suggest that most of the amylase activity in the gastric contents and a large part of the amylase activity in the intestinal contents are derived from the parotid glands, and that parotid amylase plays an important role in starch digestion in the gastro-intestinal tracts of diabetic rats.

Circadian variation of food intake and digestive tract contents in the rat.

The variation of food intake and digestive tract contents over a period of 24 hours was measured in the free feeding rat kept under a 12:12 hr light:dark cycle (lights on at 0700 hr). After a cessation between 0700 and 1000 hr, the rate of food intake increased progressively during daytime followed by a marked increase and a plateau after lights went off. In the dark, dry matter in the stomach was almost ten times the levels of the light phase. In the major part of the high feeding period, the rates of food intake and gastric emptying equilibrated. Dry matter content of the intestine also followed circadian variations that were specific for each segment. The time-to-time content of the mid-gut segment was closely related to gastric emptying. The extent of dry matter absorption in the proximal intestine decreased continuously from the time lights went on and reached a minimum at 22 hr. Absorption in the distal segments was much less subjected to variation over 24 hours. In the free feeding situation, the changes induced by the light cycle on the rhythm of food intake were accompanied by marked modifications of digestive tract contents including those of the intestine. Data indicate a close relationship between gastric function and the middle portion of the intestine.

A microregulatory analysis of spontaneous human feeding patterns.

Thirty male and 54 female students recorded in a diary exactly when and what they ate for four consecutive days. The total energy, carbohydrate, fat and protein composition of the reported meals as well as the duration of the preceding and following intermeal intervals were determined for a variety of meal definitions by a computerized analysis. A model of stomach emptying was used in conjunction with the reported intake to predict the amount of food remaining in the stomach at the beginning and end of each meal. These factors were intercorrelated across all reported meals and averaged across subjects with simple and multiple linear regression analyses. A preprandial pattern of intake regulation was found. Premeal intermeal intervals, prior food intake and the stomach content of protein and fat but not carbohydrate were significantly correlated with the amount ingested in the subsequent meal. No evidence for a postprandial pattern of intake regulation was found. The meal size, its composition and postmeal stomach content were not found to be related to the postmeal intermeal interval. No major relationships were found between subjects sex, age, weight, height or ponderal index and the meal pattern other than that males ate significantly larger meals. These results suggest that when the natural ecological constraints on human feeding behavior are present, it is regulated by adjustments to the amount eaten in a meal rather than to the duration of the interval between meals. Furthermore, the adjustment of meal size is influenced by the amount of fat and protein remaining in the stomach at the beginning of a meal.

Influence of regimen (roughage vs. concentrates) on satiety and forestomach motility in sheep.

The influence of concentrate intake on the subsequent intake of hay was investigated in sheep fitted with a rumen cannula and electrodes on the reticulum wall to measure volatile fatty acids concentration and reticular motility, respectively. In sheep fasted during night time, a previous meal of concentrates given 30, 60 or 120 min before feeding hay, did not modify significantly (p less than 0.05) the first hour and the first 3 hour intake of hay despite a large increase in ruminal total volatile fatty acid concentration. However, the daily intake of hay was significantly (p less than 0.05) reduced. Similarly, the reticular motility in response to feeding hay was not affected by the previous meals of concentrate. It is concluded that in fasted sheep on a hay ration the short-term satiation of a hay meal is not affected by foregoing intake of concentrates and that the hay intake is not controlled by ruminal volatile fatty acid levels.

A nutritive control of independent ingestion in rat pups emerges by nine days of age.

The emergence of controls of independent ingestion in rat pups was studied using nutritive (0.6 M glucose in saline or water) and vehicle gastric preloads. Two hours after preloading, ingestive responses were assessed in a 30-minute test of feeding from the floor. In 6-day-olds, all preloads had similar effects on consumption of a milk diet. In 9-day-olds, however, glucose-water preloads inhibited intake compared to water preloads. This inhibition was secondary to an effect on gastric emptying. Glucose preloads also inhibited intake in 12- and 15-day-olds. Behavioral observations indicated that feeding patterns were altered in response to glucose preloads in 9-day-olds. These results provide evidence for the emergence of a nutritive, postgastric control of independent ingestion between 6 and 9 days of age.

Is an antireflux procedure necessary in conjunction with parietal cell vagotomy in the absence of preoperative reflux?

During a 4 year period, we found no objective evidence that parietal cell vagotomy contributes to the production of gastroesophageal reflux. The fact that patients without reflux preoperatively achieved the same satisfactory clinical results whether parietal cell vagotomy was or was not accompanied by an antireflux procedure supports this view. Therefore, in the absence of reflux, we cannot recommend the prophylactic use of an antireflux procedure in combination with parietal cell vagotomy in the treatment of patients with duodenal ulcer. On the other hand, patients with duodenal ulcer should be evaluated for gastroesophageal reflux before operation because it is desirable to combine parietal cell vagotomy with an antireflux procedure if both conditions exist. Patients who have mild reflux preoperatively but no symptoms of reflux after parietal cell vagotomy alone, as in three of the four patients in Group IV, may have such symptoms subsequently. Therefore, we think that the combined procedure does not increase the morbidity over that of parietal cell vagotomy alone and recommend the combination of parietal cell vagotomy and an antireflux procedure for any patient undergoing operation for duodenal ulcer who also demonstrates an abnormal degree of gastroesophageal reflux.

Diagnosis of symptomatic alkaline reflux gastritis and prediction of response to bile diversion operation by intragastric alkali provocation.

Because accurate diagnosis of the alkaline reflux gastritis syndrome has been elusive, surgical treatment has had a high failure rate, particularly with respect to relief of pain. We have used intragastric infusion of alkali as a provocative test in 147 patients with symptoms and endoscopic findings suggestive of bile gastritis and in 19 asymptomatic control subjects. Subjects received saline solution, 0.1 normal hydrochloric acid, and 0.1 normal sodium hydroxide solutions, as well as their own gastric aspirates in random blinded fashion by a nasogastric tube. There were no complications. A positive test result was defined as pain with sodium hydroxide but not with saline solution or hydrochloric acid infusion. All of the control subjects had negative test results. A total of 87 percent of the symptomatic patients have been followed (mean 4.3 years, minimum 1 year); 47 of those 128 had a Roux-Y gastrojejunal reconstruction to divert duodenal contents from the stomach. Correlation of the test results and the subsequent clinical status showed 87 percent of those with negative test results improved spontaneously or with other treatment versus 15 percent if the test results were positive (p less than 0.001), and 78 percent of those with positive test results had lasting relief of pain after surgical diversion versus a 30 percent success rate if the test results were negative (p less than 0.01). We conclude that positive alkali infusion test results predict that symptoms will likely respond best to surgical diversion of duodenal contents, and that negative test results should be a strong deterrent to surgical diversion. The test is safe, simple, and deserves further trial.

Urine drug screening by gas chromatography-mass spectrometry. Application to a pediatric environment.

A GC-MS urine drug screening procedure is described. Its application to drug ingestion in the pediatric age group is illustrated by two case histories. The advantages and limitations of GC-MS urine drug screening are discussed.

Distribution of radiolabelled [2-14C]IQ and MeIQx in the mouse.

The kinetics of distribution of radiolabelled [2-14C]IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and [2-14C]MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) following the oral administration to BALB/c mice of single doses were studied. Both compounds were taken up into the blood-stream and other tissues rapidly after administration and approximately 20-25% of the radioactive dose of IQ or MeIQx was excreted in urine over 6 h, reflecting the rapid absorption of the mutagens. Significantly greater levels of MeIQx than IQ were isolated from the lungs and blood of treated mice. In studies of the uptake of IQ from closed sections of the gut, little IQ was absorbed from the stomach. Although there was some evidence that it could be absorbed from the large intestine, the primary site of IQ absorption was the small intestine.

Fecapentaenes and their precursors throughout the bowel--results of an autopsy study.

The fecapentaenes are potent mutagens found in the stool of some humans and pigs. These compounds are produced by Bacteroides species in the gut from an uncharacterized family of precursor compounds, and have been postulated to pose a risk of human colorectal cancer. To better understand fecapentaene production in vivo, and to determine if excreted levels measured in epidemiologic studies are representative of the entire colon, fecapentaenes were assayed from multiple sites in the bowel in an autopsy study of 16 humans and 2 pigs. An indirect measurement of fecapentaene precursors was also made. Colonic concentrations of fecapentaenes and precursors varied widely between individuals, but were consistent for each individual throughout the colon. In addition, the measurements of rectal contents, assumed to approximate values in excreted stool, were equivalent to measurements from the colon.

In vitro recovery of carbamazepine from ensure.

The in vitro recovery of three different dosage forms of carbamazepine (CBZ) when dispersed in gastric or intestinal fluids, in the presence or absence of Ensure was determined. An equivalent of 1 mg of pure CBZ from Tegretol 200 mg of conventional tablets, chewtablets of Tegretol 200-mg and Apo-carbamazepine (200-mg tablets) were dispersed in five dissolution mediums (0.5 ml of Ensure; 0.5 ml of Ensure and 1.0 ml of gastric fluid; 1.0 ml of gastric fluid; 0.5 ml of Ensure and 1.0 ml of intestinal fluid; and 1.0 ml intestinal fluid) and mixed for 1 hr and filtered. The filtrates were then assayed for CBZ using a UV spectrophotometer. The mean recoveries of CBZ for all dosage forms in the various dissolution mediums were: Ensure/gastric fluid, 85%; gastric fluid, 75%, Ensure/intestinal fluid, 59%; intestinal fluid, 79%; and Ensure, 58%. The differences in CBZ recovery from gastric or intestinal fluid, in the presence or absence of Ensure were found to be statistically significant (p less than 0.05). The difference in dosage forms were statistically not discernible. The significant differences observed in recoveries of CBZ due to Ensure warrants an in vivo study to realize the clinical implication of administering CBZ with Ensure.

Soluble lignin-carbohydrate complexes from sheep rumen fluid: their composition and structural features.

Lignin-carbohydrate complexes, isolated from cell-free rumen fluid of sheep, consisted of polyphenolic material in association with carbohydrate (5.5%) and protein (1.8%). No separation of carbohydrate from the other components could be effected. The complexes showed a bimodal distribution of molecular size with the higher-molecular-weight fraction richer in carbohydrate. Methylation analysis indicated a wide range of linkages and a high proportion of terminal sugars. Reducing sugars were found in the complexes, particularly in the low-molecular-weight fraction (approximately 25%), suggesting that ether linkages to the phenolics were also present.

HPLC determination of N-nitrosomethylurea in biological fluids by reaction with 4-nitrothiophenol.

A simple and sensitive method for the determination of N-nitrosomethylurea (NMU) in biological fluids was developed. The principle is based on the formation of 4-nitrothiophenol methyl thioether (NTP-Me) from 4-nitrothiophenol (NTP) and diazomethane formed from MNU by adding alkali. After sodium hydroxide solution was added to the mixture of NMU in aqueous solution and diethyl ether, the aqueous layer was removed and NTP was added to the ether layer in which diazomethane had been trapped. NTP-Me thus formed was determined by HPLC. This method was successfully applied to the analysis of NMU in biological samples with some clean-up. Stomach and intestine contents and blood samples from guinea-pigs were cleaned up by use of a kieselguhr column followed by heptane-water partition. The recoveries of NMU from the stomach and intestine contents were about 95% and that of NMU from blood samples was about 80%. The detection limit of NMU was 0.5 nmol/g for the stomach contents and 1 nmol/g for the intestine contents and blood samples.

Effect of ginger & garlic on DNA content of gastric aspirate.

DNA content of gastric aspirates was studied before and after intragastric infusions of three doses of ginger (2, 4, 6 g) and four doses of garlic (0.3, 0.75, 1.5, 3 g) on different days in volunteers. Only one dose was administered on any day. The mean changes of DNA-p/min in gastric aspirates after intragastric infusions of 2 and 4 g ginger were -1.37 +/- 2.3 and 6.74 +/- 3.06 respectively, which were not significant statistically. However, 6 g ginger given intragastrically showed a mean significant increase in DNA-p/min of 3.23 +/- 1.02 (P less than 0.05). Intragastric infusion of 0.3 g uncooked garlic showed a non-significant increase in DNA-p/min of 0.307 +/- 0.59. On the other hand, infusion of 0.75, 1.5 and 3 g of uncooked garlic each caused significant increase in DNA-p/min of 5.47 +/- 1.63 (P less than 0.01), 10.42 +/- 3.46 (P less than 0.01) and 29.26 +/- 4.55 (P less than 0.001) respectively. Infusion of 3 g of cooked garlic also showed significant increase in DNA-p/min of 21.43 +/- 4.62 (P less than 0.001). There was no significant difference between the effect of cooked and uncooked (3 g) garlic. Ginger in quantities of 6 g or more and garlic in quantities of 0.75 g or more cause a significant increase in exfoliation of gastric surface epithelial cells in human subjects.