Segmental colonic transit after oral 67Ga-citrate in healthy subjects and those with chronic idiopathic constipation.
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Measurement of segmental colonic transit is important in the assessment of patients with severe constipation. 111In-diethylenetriamine pentaacetic acid (DTPA) has been established as the tracer of choice for these studies, but it is expensive and not readily available. 67Ga-citrate is an inexpensive tracer and when given orally is not absorbed from the bowel. It was compared with 111In-DTPA in colonic transit studies in nonconstipated control subjects and then in patients with idiopathic constipation. METHODS: Studies were performed after oral administration of 3 MBq (81 microCi) 67Ga-citrate or 4 MBq (108 microCi) 111In-DTPA in solution. Serial abdominal images were performed up to 96 h postinjection, and computer data were generated from geometric mean images of segmental retention of tracer, mean activity profiles and a colonic tracer half-clearance time. RESULTS: There were no differences in segmental retention of either tracer or in mean activity profiles between control subjects and constipated patients. Results in constipated subjects were significantly different from those in controls. The mean half-clearance times of tracer for control subjects were 28.8 h for 67Ga-citrate and 29.9 h for 111In-DTPA in control subjects and 75.0 h for 67Ga-citrate and 70.8 h for 111In-DTPA in constipated patients. CONCLUSION: Oral 67Ga-citrate can be used as a safe alternative to 111In-DTPA for accurate measurement of segmental colonic transit. (+info)
Antinociceptive properties of the new alkaloid, cis-8, 10-di-N-propyllobelidiol hydrochloride dihydrate isolated from Siphocampylus verticillatus: evidence for the mechanism of action.
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The antinociceptive action of the alkaloid cis-8, 10-di-n-propyllobelidiol hydrochloride dehydrate (DPHD), isolated from Siphocampylus verticillatus, given i.p., p.o., i.t., or i.c.v., was assessed in chemical and thermal models of nociception in mice, such as acetic acid-induced abdominal constriction, formalin- and capsaicin-induced licking, and hot-plate and tail-flick tests. DPHD given by i.p., p.o., i.t., or i.c.v. elicited significant and dose-related antinociception. At the ID50 level, DPHD was about 2- to 39-fold more potent than aspirin and dipyrone, but it was about 14- to 119-fold less potent than morphine. Its analgesic action was reversed by treatment of animals with p-chlorophenylalanine, naloxone, cyprodime, naltrindole, nor-binaltrorphimine, L-arginine, or pertussis toxin. Its action was also modulated by adrenal-gland hormones but was not affected by gamma-aminobutyric acid type A or type B antagonist, bicuculine, or phaclofen, nor was it affected by glibenclamide. DPHD, given daily for up to 7 days, did not develop tolerance to itself nor did it induce cross-tolerance to morphine. However, animals rendered tolerant to morphine presented cross-tolerance to DPHD. The antinociception of DPHD was not secondary to its anti-inflammatory effect, nor was it associated with nonspecific effects such as muscle relaxation or sedation. DPHD, in contrast to morphine, did not decrease charcoal meal transit in mice, nor did it inhibit electrical field stimulation of the guinea pig ileum or mouse vas deferens in vitro. Thus, DPHD produces dose-dependent and pronounced systemic, spinal, and supraspinal antinociception in mice, including against the neurogenic nociception induced by formalin and capsaicin. Its antinociceptive effect involves multiple mechanisms of action, namely interaction with mu, delta, or kappa opioid systems, L-arginine-nitric oxide and serotonin pathways, activation of Gi protein sensitive to pertussis toxin, and modulation by endogenous glucocorticoids. (+info)
Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones.
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BACKGROUND: Treatment of acromegaly with octreotide increases the proportion of deoxycholic acid in, and the cholesterol saturation of, bile and induces the formation of gallstones. Prolongation of intestinal transit has been proposed as the mechanism for the increase in the proportion of deoxycholic acid in bile. AIMS: To study the effects of octreotide on intestinal transit in acromegalic patients during octreotide treatment, and to examine the relation between intestinal transit and bile acid composition in fasting serum. METHODS: Mouth to caecum and large bowel transit times, and the proportion of deoxycholic acid in fasting serum were measured in non-acromegalic controls, acromegalic patients untreated with octreotide, acromegalics on long term octreotide, and patients with simple constipation. Intestinal transit and the proportion of deoxycholic acid were compared in acromegalic patients before and during octreotide. RESULTS: Acromegalics untreated with octreotide had longer mouth to caecum and large bowel transit times than controls. Intestinal transit was further prolonged by chronic octreotide treatment. There were significant linear relations between large bowel transit time and the proportion of deoxycholic acid in the total, conjugated, and unconjugated fractions of fasting serum. CONCLUSIONS: These data support the hypothesis that, by prolonging large bowel transit, octreotide increases the proportion of deoxycholic acid in fasting serum (and, by implication, in bile) and thereby the risk of gallstone formation. (+info)
Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans.
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BACKGROUND: Prucalopride (R093877) is a selective and specific 5HT4 agonist, the first of a new chemical class of benzofurans, with gastrointestinal prokinetic activities in vitro. AIMS: To evaluate the effects of prucalopride on gastrointestinal and colonic transit. METHODS: A validated scintigraphic technique was used to measure gastrointestinal and colonic transit over 48 hours in 50 healthy volunteers. For seven days, each subject received a daily dose of 0. 5, 1, 2, or 4 mg prucalopride, or placebo in a double blind, randomised fashion. The transit test was performed over the last 48 hours. RESULTS: There were significant accelerations of overall colonic transit at 4, 8, 24, and 48 hours (p<0.05) and proximal colonic emptying t1/2 (p<0.05). The 0.5, 2, and 4 mg doses of prucalopride were almost equally effective and accelerated colonic transit compared with placebo. Prucalopride did not significantly alter gastric emptying (p>0.5) or small bowel transit (overall p=0. 12). The medication appeared to be well tolerated during the seven day treatment of healthy subjects. CONCLUSION: Prucalopride accelerates colonic transit, partly by stimulating proximal colonic emptying, but does not alter gastric or small bowel transit in healthy human subjects. Prucalopride deserves further study in patients with constipation. (+info)
Gastric emptying and intestinal transit of pancreatic enzyme supplements in cystic fibrosis.
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OBJECTIVE: To investigate gastric emptying and intestinal transit of pelleted pancreatin in relation to food boluses. METHODS: Dual isotope scintigraphy combined with breath hydrogen sampling was used to track the concurrent gastric emptying and intestinal transit of 111indium labelled microspheres and a 99mtechnetium labelled tin colloid test meal. Twelve pancreatic insufficient cystic fibrosis patients aged 5 to 38 years performed the study. RESULTS: 50% gastric emptying times showed patient to patient variation. The mean discrepancy in 50% gastric emptying times between the two labels was > 67 minutes. Mean small bowel transit time for the food bolus was prolonged at 3.6 minutes. A significant correlation was seen between weight standard deviation score and 50% emptying time for pancreatin (r = +0.73). CONCLUSION: Gastric mixing of food and pancreatin may be limited by rapid emptying of microspheres. Patients with high dosage requirements could benefit from changing the pattern of their pancreatin supplementation. (+info)
Randomised controlled trial of trophic feeding and gut motility.
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OBJECTIVES: To determine the effect of trophic feeding on gastric emptying and whole gut transit time in sick preterm infants. METHODS: A randomised, controlled, prospective study of 70 infants weighing less than 1750 g at birth, who were receiving ventilatory support, was performed. Group TF (33 infants) received trophic feeding from day 3 (0.5 ml/h if birthweight less than 1 kg, 1 ml/h if greater or equal to 1 kg) in addition to parenteral nutrition until ventilatory support finished. Group C (37 infants) received parenteral nutrition alone until ventilatory support finished. Expressed breast milk or a preterm formula were given according to maternal preference. Gastric emptying was assessed within 24 hours of nutritive milk feeding equal to 90 ml/kg/day, using ultrasound scans to measure the reduction in the gastric antral cross sectional area after a feed. Whole gut motility was assessed at both 3 and 6 weeks of age by measuring the whole gut transit time (WGTT) of the marker carmine red. RESULTS: There was no significant difference between groups in their gastric half emptying time, median difference (95% confidence interval) 2.6 (-5.9, 13.9) minutes. The WGTT was significantly faster (p < 0.05) in group TF at both 3 and 6 weeks; median difference -13 (-47, -0.1) and -12.5 (-44, -0.5) hours, respectively. CONCLUSIONS: Trophic feeding enhances whole gut motility but not gastric emptying. This effect could subsequently improve milk tolerance in sick preterm infants. (+info)
Visual parameters define the phase and the load of contractions in isolated guinea pig ileum.
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How the movements of the intestinal walls relate to luminal pressures and outflow remains incompletely understood. We triggered the peristaltic reflex in the isolated ileum of the guinea pig and quantified wall movements through computerized measurements of diameter changes. Contractions developed as indentations close to the upstream end of the loop. The indentations deepened and expanded in length. The downstream shoulder of contractions started and stopped to propagate before the upstream shoulder. Shoulders differed in their length and gradient over most of the duration of the contraction, and this gives the contraction an axial asymmetry. Over the course of individual contractions, the length of the indented segment correlated well with the luminal pressure. Contractions in response to large volumes generated long indented segments and high luminal pressures. The onset and the end of pressure waves and of outflow did not necessarily coincide with the onset and end of visual parameters of contractions. These findings indicate that objective visual parameters might be useful to describe and to classify contractions. (+info)
Modeling intermittent digesta flow to calculate glucose uptake capacity of the bovine small intestine.
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To test the hypothesis that the uptake capacity of the bovine small intestine for glucose is upregulated to match or slightly exceed glucose delivery, glucose was continuously infused into the proximal duodenum of four cannulated holstein heifers. Every 3 days, infusion rates were increased by an average of 34 mmol/h. A model of glucose disappearance from multiple boluses of intestinal digesta was used to estimate the transporter maximum velocity and functional maximum uptake capacity for the entire small intestine from average ileal glucose flows during the third day of each period. Because of its intermittency, digesta flow remained independent of simulated transit time. For each unit increase in glucose infusion rate, uptake capacity increased by only 0.55 units. Excess capacity for glucose uptake was approximately twofold in forage-fed cattle and declined to below delivery at infusions of >208 mmol/h added glucose, approximately three times the normal load. Calculations for cattle, sheep, and rats indicate that the glucose transport capacity of the small intestine is typically underutilized because of a fraction of time that transporters are not in contact with digesta. (+info)