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A reappraisal of upper gastrointestinal response to low-dose glucagon.

Although glucagon is the most commonly used pharmacologic agent for gastrointestinal studies, its exact effects on upper gastrointestinal examinations have not been properly elucidated. A large study by our group did redemonstrate glucagon's significant effect on gastrointestinal motility. However, gastric distention and coating are not improved by glucagon, nor does it have a predictable effect on gastric emptying. Duodenal visualization does appear to be enhanced by the drug. Patient age, weight, and sex are not significant factors in glucagon's response, although they are variables that have an effect on UGI examinations. This article will review physiologic considerations in upper gastrointestinal examinations, with emphasis on glucagon's pharmacodynamics.

Age Factors↗

Screening of anti-diarrhoeal profile of some plant extracts of a specific region of West Bengal, India.

Ethanol extract of four different plants of the Khatra region of the Bankura district of West Bengal, India were evaluated for anti-diarrhoeal activity against different experimental models of diarrhoea in rats. The extracts of Ficus bengalensis Linn. (hanging roots), Eugenia jambolana Lam. (bark), Ficus racemosa Linn. (bark) and Leucas lavandulaefolia Rees (aerial parts) showed significant inhibitory activity against castor oil induced diarrhoea and PGE2 induced enteropooling in rats. These extracts also showed a significant reduction in gastrointestinal motility in charcoal meal tests in rats. The results obtained establish the efficacy of all these plant materials as anti-diarrhoeal agents.

Animals↗

Erythromycin-induced dynamic ileus?

A 39-year-old man and a 79-year-old woman developed dynamic ileus soon after erythromycin stearate was administered for a respiratory tract infection. Both had had prior uncomplicated abdominal operations: the man, vagotomy and pyloroplasty for bleeding duodenal ulcer, 3 years earlier; and the woman, an appendectomy some 44 years before. The temporal association with erythromycin therapy, resolution of signs and symptoms when the drug was stopped, an uneventful recovery, and the absence of other causes, suggest a possible role of erythromycin in the pathogenesis of dynamic ileus in these patients. Disturbed gastrointestinal motility patterns caused by erythromycin, in the presence of structural changes of the alimentary tract due to prior surgical procedures, may have contributed and we review these events.

Adult↗

Prokinetic drug treatment (cisapride) is as effective as H2-blocking agent (ranitidine) in the treatment of gastric ulcer.

A double-blind, randomized, parallel-group multicenter study was conducted in 120 patients with gastric ulcer to compare cisapride, 10 mg t.i.d., and ranitidine, 150 mg b.i.d., administered over 8 weeks. No significant differences between the results of the two treatments were found in terms of ulcer healing or symptomatic relief. Endoscopy showed that the incidence of medium-sized or large ulcers was reduced from 85% at the start to 11% and 4%, respectively, after 4 and 8 weeks in the ranitidine group, and from 98% to 15% and 4%, respectively, in the cisapride group. By week 8, the ulcer was healed in 89% of the ranitidine patients, and in 86% of the cisapride patients. Moderate to severe diurnal epigastric pain--the predominant symptom--was reported by about 80% of the patients in week 8, and by less than 15% from week 4 on. The response to nocturnal epigastric pain, epigastric pressure, sensation of fullness and other symptoms was similar. Except for gastrointestinal symptoms in the cisapride patients--nearly always indicative of enhanced bowel contractions--the occurrence of adverse effects was similar in the two groups. The improvement in gastrointestinal motility under cisapride, would appear to be as effective as suppression of acid secretion in the treatment of gastric ulcer disease.

Adult↗

Salutary effects of tachykinin receptor antagonists in a rat model of postoperative ileus.

BACKGROUND: Postoperative ileus (PI) is a common surgical complication treated mainly with supportive measures. Tachykinins control gastrointestinal motility and modulate somatic and visceral pain sensation; therefore, the effect of tachykinin receptor antagonists in a rat model of PI using NK(1-3) antagonists, SR140333, SR48968, and SR142801, was investigated. MATERIALS AND METHODS: Intestinal transit was measured as Evans blue migration after varied nociceptive stimuli: skin incision (SI), laparotomy (LAP), or laparotomy plus gut manipulation (L + M) in anesthetized rats. RESULTS: Diethyl ether anesthesia and SI did not influence the intestinal transit of the dye in comparison to untreated animals--UN: 61.17 +/- 5.47, 62.10 +/- 8.30, and 56.70 +/- 4.10 cm, respectively. In contrast LAP and L + M have significantly reduced intestinal motility to 26.40 +/- 2.07 and 9.70 +/- 1.15 cm, respectively. SR140333 (3-30 microg/kg), SR48968 (1-30 microg/kg), and SR142801 (3-10 microg/kg) reversed the additional inhibitory effects of gut manipulation subsequent to LAP dose-dependently, the dye transit returning with the use of the most effective antagonist doses up to 25.28 +/- 1.08, 21.70 +/- 0.19, and 25.0 +/- 1.34 cm. The combinations of submaximal doses of NK(1) and NK(3), NK(2) and NK(3) and NK(1), and NK(2) and NK(3) antagonists were not more effective than a single-agent regimen. On the other hand SR140333 and SR48968 (NK(1) + NK(2) antagonists) acted additively, the intestinal transit reaching 26.60 +/- 0.85 cm. SR140333, SR48968, and SR142801 have not affected the intestinal passage in UN rats or those undergoing SI or LAP. CONCLUSIONS: SR140333, SR48968, and SR142801 exert a salutary action on suppressed gut motility following surgical manipulation of the gut, the combination of NK(1) and NK(2) antagonists being most beneficial.

Anesthetics, Inhalation↗

The role of neurotensin in disease.

Current thinking concerning the possible role off neurotensin in disease is reviewed. The type of approach used in this article is to summarize the results of studies concerning release of neurotensin-like immunoreactivity and to describe the effects of neurotensin which may be of physiological significance such as changes in gastrointestinal motility from a fasting to a fed type in gastric acid secretion and vasoconstriction in adipose tissue. The possible involvement of neurotensin in motility disturbances, duodenal ulcer and obesity has also been discussed. In addition, studies concerning the role of neurotensin in endocrine tumours are presented.

Adipose Tissue↗

[Small bowel bacterial overgrowth syndrome in chagasic megajejunum: report of 2 cases].

We report two cases of Chagas' disease with megacolon who presented with chronic diarrhea. One of the patients also had evidence of malabsorption, such as steatorrhea and hypocalcemia. Barium meal follow-through showed remarkable dilation of the jejunum in both cases and, in one of them, an associated megaduodenum. Manometric studies of gastrointestinal motility showed abnormally slow propagation of the interdigestive migrating motor complex, which was also excessively prolonged. Cultivation of jejunal aspirates revealed strict anaerobic bacterial growth in both cases. Oral antibiotic therapy led to substantial improvement in symptoms. The two cases herein reported indicate that clinical manifestations of small bowel bacterial overgrowth, possibly caused by motor disturbances associated with megajejunum, may occasionally include the clinical picture of gastrointestinal involvement in Chagas' disease.

Adult↗

Permanent jejunal fistula: promising method for obtaining small intestinal chyme without disturbing intestinal function.

Accurate information on changes in small intestinal microflora in dogs is rather limited because of difficulties in obtaining samples of small intestinal chyme. In the study reported here, intussuscepted nipple valves were surgically placed into the jejunum of seven laboratory beagles to obtain intestinal juice samples. The influence of the fistula on intestinal motility was determined by use of barium-impregnated polyethylene spheres (BIPS) and on microflora by use of bacterial culturing. The BIPS were fed two weeks before surgery and again five weeks after surgery. Bacterial samples were collected before (fecal samples), during (small intestinal samples) and 11 weeks after surgery. There were no surgical complications, and the animals tolerated the fistula well. Mean orocolic transit percentage was 93% before and 83% after surgery, and notable changes in gastrointestinal motility were not seen, except in one dog. The surgery did not markedly alter the bacterial flora in feces. Microflora did change in small intestinal samples; however, methodologic factors may explain most of these differences. In conclusion, the nipple valve is a promising method that creates easy and safe long-term access to the jejunum and appears not to have an influence on intestinal function.

Animals↗

[The changes of electrogastrogram and gastrointestinal pressure following cholecystectomy].

OBJECTIVE: To investigate the mechanism and pathophysiological changes after abdominal surgery. METHOD: Twenty-two patients after cholecystectomy were selected to perform cutaneous electrogastrography (EGG) at least one hour before operation, and the first, the second and the third day after operation respectively. On the operative and postoperative days, gastroduodenojejunal manometry was performed in 17 of the 2 patients. RESULT: The percentage of EGG normal frequency on the operative day was obviously lower than that on the preoperative day (P < 0.001), and the percentage of bradygastria on the operative day was obviously higher than that on the preoperative day (P < 0.01). The postoperative EGG amplitude was obviously lower than the preoperative one (P < 0.001), and did not recover after three days. The phase III of the migrating motor complex (MMC) appeared within 24 hours after operation, and first appeared at the duodenum. MMC III was most vigorous at the duodenum in recording period, and was less at the antrum. The contractile power and the area of MMC III at antrum after operation were obviously lower than at duodenum and upper jejunum (P < 0.01). On the third day after operation, the contractile power was lower than normal (P < 0.01). CONCLUSION: Gastrointestinal motility dysfunction after cholecystectomy is related to EGG amplitude, and not to EGG frequency. The recovery of antrum MMC III is later than that of small bowl, resulting in delayed gastric emptying. The MMC III of small bowl resums in early period after abdominal surgery. Postoperative ileum is due the decrease of MMC III contractile power and the area after abdominal surgery, which represent the ability of gastrointestinal contraction.

Adult↗

Peptides that regulate food intake: somatostatin alters intake of amino acid-imbalanced diets and taste buds of tongue in rats.

The present studies were designed to evaluate a potential dose-dependent effect of somatostatin (SRIF) administered peripherally on intake of either a low-protein basal diet or threonine-imbalanced diet (THR-IMB), on body weight gain (DeltaBW), gut motility, and on the histology of taste buds in rats. SRIF administration had a dual effect related to its concentration, increasing the intake of THR-IMB diet at low concentration and decreasing THR-IMB diet at high concentration. During the light phase, SRIF treatment increased the intake of THR-IMB diet, suggesting that the usual anorectic effect induced by intake of THR-IMB diet was attenuated. High-dosage SRIF decreases gastrointestinal motility, which, in turn, can decrease food intake and DeltaBW. The combination of THR-IMB diet regimen and SRIF treatment also induced significant modifications on the taste buds of the tongue. The feeding response to an amino acid-imbalanced diet includes a learned aversion to the diet, and animals may use taste in establishing that aversion. Modifications of taste buds of SRIF-treated rats eating THR-IMB diet might explain the increase of imbalanced diet intake if treated rats perceive this food as less aversive.

Amino Acids↗

[Synaptic processes in smooth muscles].

Junction potentials evoked by intramural stimulation were investigated in smooth muscles of guinea-pig gastrointestinal tract by means of intracellular recording and sucrose-gap methods. It was shown that cholinergic nerve-muscle transmission is only excitatory and more effective in fundic smooth muscles as compared with other part of the gut. Adrenergic nerve control of gastrointestinal motility is carried out both by excitation and inhibition of the smooth muscles. Nonadrenergic inhibition was observed in circular muscle layer of all parts of the gut and was more effective in distal colon. Noncholinergic, nonadrenergic excitation in caecum smooth muscles is shown to be of complex nature. It consists of an initial excitatory junction potential followed by a slow late wave of depolarization. In other parts of the gastrointestinal tract such an excitation is manifested only by a slow late wave of depolarization.

Adrenergic Fibers↗

Evaluation of anti-diarrheal activity of Cleome viscosa L. extract in rats.

A study was undertaken to evaluate the effect of a methanol extract of the entire plant Cleome viscosa L. (CVME) (Family; Capparidaceae) for its anti-diarrheal potential against some of the experimental models of diarrhea in rats. CVME showed significant inhibitory activity against castor-oil-induced diarrhea and PGE2 induced enteropooling in rats. The extract also showed a significant reduction in gastrointestinal motility in the charcoal meal test in rats. The results obtained establish the efficacy and substantiate the folklore claim as an anti-diarrheal agent.

Animals↗

Role of prokinetic drugs for treatment of postoperative ileus in the horse.

All horses undergoing coeliotomy for an acute abdominal crisis are at risk of developing ileus and should receive therapy aimed at promoting gastrointestinal function by restoring fluid and electrolyte balance. Adequate analgesia and prevention against peritonitis, bacteraemia and endotoxaemia should be provided. Horses that at the time of surgery have a strangulating or non-strangulating small intestinal obstruction should be considered to be at greater risk of developing a persistent ileus that is refractory to treatment than those horses with lesions involving the large intestine. In horses considered to be at greater risk of developing a persistent ileus, the use of prokinetic agents should be considered. Agents that may be used to improve gastrointestinal motility include adrenergic receptor antagonists, cholinergic agonists, benzamides, dopamine antagonists, macrolide antimicrobials, opiate receptor agonists and antagonists, somatostatin analogues and local anaesthetics. There are limited studies into the use of these agents in the horse. Until further research provides more information on motility disorders following intestinal surgery and the efficacy of prokinetic agents in this species, only selective use of some of these drugs can be recommended.

Adrenergic Antagonists↗

Regulation of 60-kDa heat shock protein expression by systemic stress and 5-hydroxytryptamine in rat colonic mucosa.

Bowel dysfunction such as irritable bowel syndrome caused by stress is well described. Previous reports suggest that 5-hydroxytryptamine (5-HT) mediates alteration of bowel motility. In this study, the effects of water-immersion stress and the administration of 5-HT on the expression of a 60-kDa heat shock protein (HSP60) in rat colonic mucosa were investigated. The effect of YM-060, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, on the expression of this protein was also studied. Water-immersion stress and the administration of 5-HT induced synthesis of HSP60 in rat colonic mucosa. The induction of HSP60 and the number of defecations were clearly inhibited by the oral administration of YM-060. Our results suggest that the induction of HSP60 in rat colonic mucosa by water-immersion stress may be associated with gastrointestinal motility mediated by 5-HT, especially via 5-HT3 receptors.

Animals↗

[Mode of action of trimebutine: involvement if opioid receptors].

Several studies in dogs, cats, rabbits and humans have suggested that the motility-stimulating properties of trimebutine (TMB) are mediated by peripheral opiate receptors. The present work deals with the capacity of the drug and its N-desmethyl metabolite (NDTMB) to displace mu, delta and kappa specific ligands from their receptors using guinea-pig whole brain membranes and ileum myenteric plexus synaptosomes membranes. The activity of both compounds on the twitch response induced by transmural stimulation of the guinea-pig ileum and of the mouse and rabbit vas deferens was also investigated. These preparations have been claimed to be specific for the mu, delta and kappa receptor subtypes respectively. TMB (0.2 to 1.8 microM) and NDTMB (0.3 to 6 microM) displayed a good affinity for all receptor subtypes in brain and myenteric plexus preparations. The decreasing order of IC50 (50 per cent inhibitory concentration)'S of TMB ranged from 0.75 microM in the guinea-pig ileum to 7.1 and 39 microM in the vas deferens of the rabbit and the mouse respectively. These results indicate that TMB and NDTMB possess mu, delta as well as kappa agonistic properties without true specificity for one or the other of these subtypes. They also confirm that activation of peripheral mu, delta and kappa opiate receptors mediate the gastrointestinal motility effect of TMB.

Animals↗

Somatostatin administration modifies food intake, body weight, and gut motility in rat.

The effects of a long period of relatively high and nearly constant levels of Somatostatin (SRIF) on the control of food ingestion and body weight gain were investigated; weight gain occurs via concurrent modifications of food and fluid intake and in vitro gut motility. Fluid intake was not influenced by SRIF treatment. Food intake, body weight, body weight gain, and gut motility decreased after SRIF treatment, and, in some cases, these effects were dose-dependent. Food intake increased significantly during light phase of SRIF treatment. Thus, SRIF treatment produces facilitation of food intake in the light and inhibition in the dark. The suppression seen in the dark may be the result of a preferential activation of the inhibitory response. The increase of food intake during the light may be explained by a decreased availability of body fats as fuels for metabolism since SRIF inhibits GH release, which is involved is the breakdown of adipose tissue into fuels; lower fats synthesis during nocturnal feeding; or both. Decreased gastrointestinal motility also may explain the lower food intake and decreased body weight gain following SRIF treatment.

Animals↗

Anti-diarrhoeal evaluation of Clerodendrum phlomidis Linn. leaf extract in rats.

A study was undertaken to evaluate the effect of methanolic extract of leaves of Clerodendrum phlomidis Linn. (MECP) (Family: Verbenaceae) for its anti-diarrhoeal potential against several experimental models of diarrhoea in Wistar albino rats. MECP showed significant inhibitory activity against castor oil induced diarrhoea and PGE2 induced enteropooling in rats. The extract also showed a significant reduction in gastrointestinal motility in charcoal meal test in rats. The results obtained establish the efficacy and substantiated the folklore claim as an anti-diarrhoeal agent.

Animals↗

Botulinum toxin for spastic gastrointestinal disorders.

Botulinum toxin (BTX) is one of the most potent inhibitors of acetylcholine from nerve endings, and this accounts for its toxic properties as well as its therapeutic application in a variety of neuromuscular syndromes. This review focuses on the growing use of BTX in the so-called 'spastic' disorders of the gastrointestinal tract. These include achalasia, for which the short-term efficacy of the intrasphincteric injection of BTX has been well established. However, because of the chronicity of this condition, repeated injections of the toxin may be required at regular intervals. In contrast, the relatively short duration of action may be an advantage in disorders such as chronic anal fissure, where the benefit of this therapy has now been demonstrated in hundreds of patients. There are many other sphincteric and non-sphincteric syndromes in the gut for which the efficacy of this agent is being actively tested. These include non-cardiac chest pain, post-operative pylorospasm and sphincter of Oddi dysfunction. Skeletal muscle sphincters, such as the upper oesophageal sphincter or the external anal sphincter/puborectalis muscle, may also be targeted, with good effect. In some of these conditions, the local injection of BTX may serve as a useful therapeutic trial, facilitating the decision to institute more invasive forms of therapy. The cumulative short-term experience with BTX in the gut to date suggests that it is a relatively simple and safe therapy. The use of BTX represents a novel approach for gastrointestinal motility disorders, and the rapidly expanding list of successful applications holds promise for a more widespread use of similar agents in the future. Additional studies on long-term outcome are eagerly awaited.

Botulinum Toxins↗