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PubMed1993

Erythromycin: a motilin agonist and gastrointestinal prokinetic agent.

Erythromycin, a commonly used antibiotic, has recently emerged as a potential gastrointestinal prokinetic agent. This follows a decade of research into the mechanism of well-recognized gastrointestinal side effects of erythromycin. Early investigations demonstrated that erythromycin increased gastrointestinal motility, and more recent studies suggest that it fortuitously binds to and stimulates the receptor for the gastrointestinal peptide motilin. From this work it appears that a new and powerful class of gastrointestinal prokinetic agents will evolve from erythromycin and its derivatives. The role of motilin in the genesis of the fasting and fed patterns of gastrointestinal motility is emerging through the study of these motilin agonists.

Animals↗
PubMed1987

Gastric emptying after Roux-Y and Billroth-I gastrectomy depends on viscosity of meal and contractile patterns of small intestine in dogs.

The aim of the study was to examine gastrointestinal motility after distal gastrectomy and the influence of meal viscosity on gastric emptying. Gastrointestinal motility and gastric emptying of acaloric meals with different viscosities were measured in normal dogs and after a two-thirds gastrectomy with Billroth-I or Roux-Y gastroenterostomy. After distal gastrectomy, gastric emptying depended on the viscosity of the meal, as in normal dogs. Acaloric viscous meals emptied significantly faster in the Billroth-I than in the Roux-Y group due to different contractile patterns of the duodenum and jejunum. In comparison to normal dogs, gastric emptying of viscous meals was accelerated in the Billroth-I and delayed in the Roux-Y group. Several motility parameters of the stomach and intestine differed between the normal and gastrectomized dogs. Thus, after distal gastrectomy, the viscosity of the meal and the contractile patterns of the small intestine are important determinants of gastric emptying.

Animals↗
PubMed1999

Severe respiratory depression in a patient with gastroparesis while receiving opioids for pain.

OBJECTIVE: To increase awareness of the possibility of severe respiratory depression when oral opioids are used in patients with gastrointestinal motility disorders. SETTING: A major county hospital affiliated with a university. PATIENT: A patient with severe pain from diabetic muscle necrosis with a history of gastroparesis. INTERVENTIONS: Attempted pain control with oral and transdermal opioids. RESULTS AND CONCLUSIONS: Pain control in our patient was attempted using potent oral opioids on two occasions. However, this patient suffered severe respiratory depression after each attempt. Transdermal delivery of fentanyl eventually provided satisfactory pain relief without side effects. We conclude that patients with gastrointestinal motility disorders may be at high risk for side effects of oral opioids due to altered absorption kinetics. Suggestions are made for alternative strategies for opiate delivery in patients with gastrointestinal motility disorders.

Administration, Cutaneous↗
PubMed1987

The effect of an oral gold preparation on the gastrointestinal tract motility in two species of experimental animals.

The oral gold preparation, auranofin, used in rheumatoid arthritis has been reputed to cause chronic diarrhea. To investigate this the G.I. tract motility was measured before auranofin therapy and after 1, 3, and 5 weeks of therapy using scintigraphy following indium-111-labeled meals in three beagle dogs. The gastric emptying times of the dogs accelerated throughout the duration of the experiment, although the large bowel transit times did not seem to be affected. The affect of auranofin on the stools of the baboon Papio ursinus was also noted. The baboon stools were observed for any change in consistency. Sigmoidoscopic examination including mucosal biopsies was carried out monthly over a 6-month period. The baboon's stools were noted to become very soft in consistency, but histology indicated no mucosal changes.

Administration, Oral↗
PubMed1989

Autonomic function and motility in intestinal pseudoobstruction caused by paraneoplastic syndrome.

This report documents the occurrence of chronic intestinal pseudoobstruction in association with a small cell carcinoma of the lung with evidence of pre- and postganglionic sympathetic dysfunction in one patient with brain metastases, and with sympathetic and parasympathetic postganglionic dysfunction in a second patient. A strategy is outlined for the identification and characterization of disordered neural control of gut motility. This strategy utilizes gastrointestinal motility studies to confirm gut neuropathy, autonomic function tests, and plasma norepinephrine responses to intravenous edrophonium to identify the level of dysfunction. These cases are compared with others in the literature, and the occult nature of these cancers, the spectrum of symptoms suggesting autonomic dysfunction on presentation, and the occasional response of the neurologic deficit to treatment of the malignancy are highlighted.

Autonomic Nervous System Diseases↗
PubMed2004

Effect of aqueous leaf extract of Irvingia gabonensis on gastrointestinal tract in rodents.

Effect of the aqueous leaf extract of I. gabonensis on the gastrointestinal tract was investigated on isolated rabbit jejunum, guinea pig ileum, gastrointestinal motility, castor oil-induced diarrhoea in mice and castor oil-induced fluid accumulation in rats. The results showed that the extract exhibited a concentration-dependent relaxation of spontaneous pendular movement of isolated rabbit jejunum and guinea pig ileum, and attenuated both acetylcholine-induced contraction of rabbit jejunum and histamine-induced contraction of guinea pig ileum. The extract (100, 200 and 400 mg/kg) also caused a significant dose-dependent decrease of gastrointestinal motility in mice (40.12, 39.45 and 37.45%), intestinal fluid accumulation in rats (71.43, 81.63 and 83.27%), and remarkably protected mice against castor oil-induced diarrhoea [58.33, 75 and 91.67% (Di Carlo score)] respectively. Preliminary phytochemical screening of the aqueous leaf extract of I. gabonensis revealed the presence of saponins, tannins, phenols and phlobatanins.

Animals↗
PubMed1992

Upper gastrointestinal tract motility in children with progressive muscular dystrophy.

Gastric emptying was evaluated in 15 children (mean age, 8.0 years) with progressive muscular dystrophy to detect early gastrointestinal smooth muscle involvement; 10 of the children also underwent esophageal manometry. Clinical evidence of skeletal muscle dysfunction was minimal in 14 of the 15 patients; 10 of them had no gastrointestinal symptoms. Gastric emptying studies were performed by using 500 muCi of technetium 99m-sulfur colloid bound to a scrambled egg, and scintigraphic measurements were made continuously for 60 to 90 minutes. Gastric emptying studies and manometric tracings were compared with those from 11 children (mean age, 8.4 years) without gastrointestinal or muscular disorders. Mean (+/- SD) percentage retention of gastric isotope was significantly greater in patients with muscular dystrophy than in control subjects. No differences were found between the two groups in distal esophageal motility or in upper and lower esophageal sphincter pressures or relaxation. Contraction amplitudes in the upper portion of the esophagus, however, were significantly lower in patients with myopathy than in control subjects. These data suggest that dysfunction of smooth muscle of the upper gastrointestinal tract is detectable in children with muscular dystrophy early in the course of the disease, even when gastrointestinal symptoms are absent and skeletal muscle symptoms are minimal.

Adolescent↗
PubMed2006

Biologic clocks and the gut.

The gastrointestinal tract displays biologic rhythms in basal gastric acid output, epithelial cell proliferation, gastrointestinal motility, and appetite regulation. Furthermore, the development of gastrointestinal complications after administration of aspirin and after chemo- and radiotherapy for metastatic colon cancer depends on the time of administration. Biologic rhythms are driven by so-called clock genes. Thus, it is conceivable that subsets of genes in the gastrointestinal tract are under clock gene control as well. The purpose of this article is to discuss basic concepts in the studies of biologic rhythms, to review examples of biologic rhythms in the gastrointestinal tract, and to discuss examples of gastrointestinal diseases in which alterations in biologic rhythms may play a pathogenetic role.

Animals↗
PubMed2004

In vivo and in vitro study of the influence of the anticholinesterase drug galantamine on motor and evacuative functions of rat gastrointestinal tract.

Galantamine is efficacious for vascular dementia and Alzheimer's disease. Its application leads to some negative gastrointestinal side effects. The present study observes galantamine-induced influence on gastrointestinal motility of rats and its effects on isolated gastrointestinal smooth muscles. The gastrointestinal tract was studied by X-ray contrast examination. Functional disturbances were observed: hypertonia, increased stomach and ileal peristalsis activity, accelerated intestinal passage. In vitro, the drug caused tonic contractions in smooth muscle preparations and increased the gastric and ileal phasic amplitude. The jejunal smooth muscle strips demonstrated an opposite tendency. The reactions were a result of the interaction of galantamine-accumulated endogenic acetycholine with M- and N-acetylcholine receptors. The tonic effects were influenced in varying degree by atropine and ipratropium, whereas the phasic by atropine, ipratropium, hexametonium and methysergide. In conclusion, the in vitro effects registered satisfactorily explain in vivo examined galantamine-induced changes in the gastrointestinal tract of the treated rats and can be considered as main cause for development of such changes.

Animals↗
PubMed2004

IRAG is essential for relaxation of receptor-triggered smooth muscle contraction by cGMP kinase.

Signalling by cGMP-dependent protein kinase type I (cGKI) relaxes various smooth muscles modulating thereby vascular tone and gastrointestinal motility. cGKI-dependent relaxation is possibly mediated by phosphorylation of the inositol 1,4,5-trisphosphate receptor I (IP(3)RI)-associated protein (IRAG), which decreases hormone-induced IP(3)-dependent Ca(2+) release. We show now that the targeted deletion of exon 12 of IRAG coding for the N-terminus of the coiled-coil domain disrupted in vivo the IRAG-IP(3)RI interaction and resulted in hypomorphic IRAG(Delta12/Delta12) mice. These mice had a dilated gastrointestinal tract and a disturbed gastrointestinal motility. Carbachol- and phenylephrine-contracted smooth muscle strips from colon and aorta, respectively, of IRAG(Delta12/Delta12) mice were not relaxed by cGMP, while cAMP-mediated relaxation was unperturbed. Norepinephrine-induced increases in [Ca(2+)](i) were not decreased by cGMP in aortic smooth muscle cells from IRAG(Delta12/Delta12) mice. In contrast, cGMP-induced relaxation of potassium-induced smooth muscle contraction was not abolished in IRAG(Delta12/Delta12) mice. We conclude that cGMP-dependent relaxation of hormone receptor-triggered smooth muscle contraction essentially depends on the interaction of cGKI-IRAG with IP(3)RI.

Animals↗
PubMed2002

Small intestinal manometry.

Gastrointestinal motility is an integrated process including myoelectrical and contractile activity, tone, compliance and transit. The techniques for the assessment of gastrointestinal motility are multiple and all have their advantages and disadvantages. In the case of suspected abnormal upper gut transit, gastric and small bowel transit scintigraphy followed by small intestinal (antroduodenojejunalileal) manometry is recommended. Small bowel manometry can identify patterns suggestive of myopathy, neuropathy or obstruction. Information on procedures, indications, significance, pitfalls and guidelines for small bowel manometry is provided in this paper. In this context the potentials of small intestinal manometry for scientific experimental study of neurohumoral agents, such as serotonin receptor agonists and antagonists, on small intestinal motility is presented.

Enteric Nervous System↗
PubMed1989

[Recurrent gastroparesis following abdominal irradiation. Therapy with cisapride].

Following abdominal radiation a 16-year-old male patient developed nausea and vomiting secondary to gastric stasis, dilatation and impairment of antral motility. Symptoms improved after 2 months of treatment with a cholinergic agonist. Now, 7 years later, symptoms recurred. Cisapride, a newly developed agent which stimulates gastrointestinal motility probably evoked a prompt increase of antral motility and gastric emptying. We conclude that abdominal irradiation may cause gastrointestinal motility disturbances which may respond to medical therapy.

Adolescent↗
PubMed2006

Preliminary pharmacological screening of Bixa orellana L. leaves.

Preliminary pharmacological studies were performed on the methanol extract of Bixa orellana L. (Bixaceae) leaves to investigate neuropharmacological, anticonvulsant, analgesic, antidiarrhoeal activity and effect on gastrointestinal motility. All studies were conducted in mice using doses of 125, 250 and 500 mg/kg of body weight. In the pentobarbitone-induced hypnosis test, the extract statistically reduced the time for the onset of sleep at 500 mg/kg dose and (dose-dependently) increased the total sleeping time at 250 and 500 mg/kg dose. A statistically significant decrease in locomotor activity was observed at all doses in the open-field and hole-cross tests. In the strychnine-induced anticonvulsant test, the extract increased the average survival time of the test animals (statistically significant at 250 and 500 mg/kg). The extract significantly and dose-dependently reduced the writhing reflex in the acetic acid-induced writhing test. Antidiarrhoeal activity was supported by a statistically significant decrease in the total number of stools (including wet stools) in castor oil-induced diarrhoea model. A statistically significant delay in the passage of charcoal meal was observed at 500 mg/kg in the gastrointestinal motility test. The extract was further evaluated in vitro for antioxidant and antibacterial activity. It revealed radical scavenging properties in the DPPH assay (IC(50)=22.36 microg/ml) and antibacterial activity against selected causative agents of diarrhoea and dysentery, including Shigella dysenteriae.

Acetic Acid↗
PubMed1997

Pathophysiology of adynamic ileus.

We hypothesized that the inhibitory neurotransmitters nitric oxide (NO) and vasoactive intestinal peptide (VIP) may play a role in the disrupted gastrointestinal motility of endotoxemia. Strain gauge transducers on the stomach and small intestine of dogs determined interdigestive gastrointestinal motility. Tissue levels of NO synthase and VIP and serum levels of nitrite/nitrate (NO(2)-/NO(3)-) and VIP were measured. Following completion of the baseline studies, dogs were given a single dose of E. coli lipopolysaccharide, 200 microg/kg intravenously, and the studies were repeated for the next three days. Following endotoxin bolus, the migrating motor complex (MMC) was delayed for two days while serum VIP was increased on postendotoxin day 1 and serum NO(2)-/NO(3)- was increased on postendotoxin day 2. There were no changes in gut smooth muscle levels of NO synthase or VIP. We conclude that a single, sublethal dose of endotoxin results in prolongation of the MMC with distinct but independent increases in serum levels of VIP and NO(2)-/NO(3)-.

Animals↗
PubMed1994

[Adaptation and effects of ileal reservoir on ileo-proctostomy following total colectomy in dogs].

We examined postoperative adaptation and effects of J-pouch reservoir on ileo-proctostomy following total colectomy in dogs. End to end (E-E; n = 5) or J-pouch (J-P; n = 5) anastomosis was performed after resection of total colon and the rectum 3 cm above the peritoneal reflexion. Gastrointestinal motility with strain gauge force transducers (SG) and transit time with barium meal under the fluoroscopy were recorded 6 months after total colectomy. Then, histological changes of seven specimens from totally resected ileum in J-P and E-E vs control (normal ileum; n = 5) were measured with hematoxylin-eosin and PYY immunohistochemical stains. Propagation rate of interdigestive migrating complex (IMC) from jejunum to ileum was significantly lower in J-P (64.8 +/- 13.2%) than in E-E (98.6 +/- 1.2%) (p < 0.001). Oro-neorectal transit time (ONTT) in E-E (138 +/- 10 min) was shorter (p < 0.05), but ONTT in J-P (189 +/- 26 min) was significantly longer (p < 0.01) than oro-caecal transit time (OCTT) in preoperative control (165 +/- 19 min; n = 10). There was no difference about length of villi among control, E-E and J-P, but length of crypts in J-P (0.59 +/- 0.08 mm) was longer than that in E-E (0.27 +/- 0.02 mm) and normal ileum (0.34 +/- 0.07 mm) (p < 0.01). PYY positive cells in J-P were more than in E-E and control at any site of ileum and total number of PYY positive cells in J-P (168 +/- 18) significantly increased than that in E-E (111 +/- 16) and control (103 +/- 14) (p < 0.05). Thus, increase of PYY positive cells in J-P inhibits gastrointestinal motility and transit. Delayed transit time and crypts elongation were intestinal adaptation that assists the absorption of luminal contents. Therefore, it suggested that J-pouch reservoir had advantage to ileo-proctostomy following total colectomy in dogs.

Adaptation, Physiological↗
PubMed1995

Increased plasma levels of pancreatic polypeptide and decreased plasma levels of motilin in encopretic children.

OBJECTIVE: Abnormalities of hormones affecting gastrointestinal motility have been found in "functional" disorders of the gastrointestinal system in adults. One such disorder of childhood, encopresis, is frequently associated with constipation, the treatment of which often eliminates the soiling. We hypothesized that hormones affecting gastrointestinal motility were different between encopretic patients and matched controls. METHODS: Ten encopretic patients were matched by age, race, and sex with controls who had no history of encopresis or constipation. After an overnight fast, each child consumed a meal of Ensure, the amount of which was based on body weight. Plasma levels of gastrin, pancreatic polypeptide, cholecystokinin, motilin, thyroxine, estrogen, and insulin were measured 20 and 5 minutes before the meal, and 5, 10, 15, 30, 45, 60, 90, 120, 150, and 180 minutes after the meal. RESULTS: Postprandial levels of pancreatic polypeptide remained consistently higher and peaked earlier (P < .05) for encopretic patients. The motilin response was lower (P < .03) for encopretic children than for controls. CONCLUSIONS: We conclude that pancreatic polypeptide and motilin responses to a meal are different in encopretic children than in children in the control group. These gastrointestinal hormone findings may in part explain and/or be the result of the severe constipation that frequently underlies the fecal soiling found in these patients. These findings also suggest the motility of the stomach and small intestine may be abnormal in encopresis.

Adolescent↗
PubMed2006

Tachykinin receptors as drug targets for motility disorders.

The tachykinins and their receptors are strategically distributed within the gut wall, spinal cord, and central nervous system to be potential targets of therapeutic agents for gastrointestinal motility disorders. However, the development of effective tachykinin receptor agonists or antagonists to treat these disorders has had very limited success so far. This is, in part, due to the complex and multilevel of regulation of gastrointestinal motility function and the challenges faced in targeting the specific type of gut contraction to normalize function in disease state.

Animals↗
PubMed2002

Comparison of recovery of gastric phase III motility and gastric juice output after different types of gastrointestinal reconstruction following pylorus-preserving pancreatoduodenectomy.

BACKGROUND: Early gastric stasis is a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD). However, few reports have addressed this phenomenon in relation to the type of gastrointestinal reconstruction. We compared gastrointestinal motility and gastric juice output after two different types of gastrointestinal reconstruction following PPPD, end-to-side duodenojejunostomy after pancreaticojejunostomy and hepaticojejunostomy (group 1) and end-to-end duodenojejunostomy before pancreaticojejunostomy and hepaticojejunostomy (group 2). METHOD: In a total of 25 patients, 10 in group 1 and 15 in group 2, who underwent PPPD, manometry was repeated to assess gastric and jejunal motility until the first occurrence of phase III activity of gastric cyclic motor activity (CMA). The plasma level of motilin was measured in each phase of the gastric CMA and compared between the two groups. The daily volume of gastric juice output through a gastrostomy tube was also recorded for comparison. RESULT: There was no significant difference in the time period for recovery of gastric phase III activity and gastric juice output between the two groups. However, abnormal contractions with an increased basal pressure appeared frequently in the afferent jejunal loop only in group 1. The plasma motilin level after PPPD showed no apparent cyclic change even after the recovery of gastric phase III in either group. CONCLUSION: Gastrointestinal reconstructive procedures have almost no effect on the recovery of gastric CMA. The plasma motilin concentration does not play a major role in the recovery of gastric CMA in the early postoperative period after PPPD.

Adult↗