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PubMed1996

EM523L, a nonpeptide motilin agonist, stimulates gastric emptying and pancreatic polypeptide secretion.

We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.

Adult↗

PubMed2003

Effects of neurotrophins on gastrointestinal myoelectric activities of rats.

AIM: To observe the effects of mouse nerve growth factor (NGF), rat recombinant brain derived neurotrophic factor (rm-BDNF) and recombinant human neurotrophin-3 (rh-NT-3) on the gastrointestinal motility and the migrating myoelectric complex (MMC) in rat. METHODS: A randomized, double-blinded, placebo-controlled experiment was performed. 5-7 days after we chronically implanted four or five bipolar silver electrodes on the stomach, duodenum, jejunum and colon, 21 experimental rats were coded and divided into 3 groups and injected NGF, rm-BDNF, rh-NT-3 or placebo respectively via tail vein at a dose of 20 microg x kg(-1). The gastrointestinal myoelectrical activity was recorded 2 hours before and after the test substance infusions in these consciously fasting rats. RESULTS: The neurotrophins-induced pattern of activity was characterized by enhanced spiking activity of different amplitudes at all recording sites, especially in the colon. In the gastric antrum and intestine, only rh-NT-3 had increased effects on the demographic characteristics of electrical activities (P<0.05), but did not affect the intervals of MMCs. In the colon, all the three kinds of neurotrophins could significantly increase the frequency, amplitude and duration levels of spike bursts, and also rh-NT-3 could prolong the intervals of MMC in the transverse colon (25+/-11 min vs 19+/-6 min, P<0.05). In the distal colon rh-NT-3 could evoke phase III-like activity and disrupt the MMC pattern, which was replaced by a continuously long spike bursts (LSB) and irregular spike activity (ISA) for 48+/-6 min. CONCLUSION: Exogenous neurotrophic factors can stimulate gut myoelectric activities in rats.

Animals↗

PubMed2006

Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal transit in healthy volunteers.

Although malabsorption of small amounts of fructose-sorbitol mixtures occurs frequently in healthy humans, insights into their effects on gastrointestinal motility are poor. The present study addresses the hypothesis that malabsorption of a fructose-sorbitol challenge changes the small intestinal transit rate. Eleven healthy volunteers participated in a double-blind crossover investigation. In random order, the subjects ingested 30 g glucose or a mixture of 25 g fructose and 5 g sorbitol as 10% solutions. As a radiolabeled marker, (99m)Tc-diethylenetriaminepentaacetic acid was added to each test solution. Breath hydrogen and methane concentrations and gastrointestinal progress of the radiolabeled marker were followed for the next 6-hr period. Malabsorption of small amounts of the fructose-sorbitol mixture was evident in all subjects. The area under the gastric radioactivity-time curve after ingestion of glucose did not differ from that after ingestion of the fructose-sorbitol mixture (P = 0.7897). However, the mouth-to-cecum transit of the radiolabeled marker was faster (P = 0.0033) and the percentage content of the marker in colon was higher after ingestion of the fructose-sorbitol mixture than after ingestion of glucose (P = 0.0128). In healthy humans, malabsorption of small amounts of a fructose-sorbitol mixture accelerates small bowel transit.

Adult↗

PubMed1997

Gastric emptying time in patients with primary hypothyroidism.

BACKGROUND AND OBJECTIVES: Symptoms due to slowing of gastrointestinal motility constitute an important problem in most patients with primary hypothyroidism. The purpose of this study was to calculate gastric emptying time in patients with primary hypothyroidism using a radioisotopic method. PATIENTS AND METHODS: Fifteen hypothyroid patients (2 male, 13 female) participated in the study. Mean age was 43 (range 38-50) years. Only patients who had been recently diagnosed and had received no previous therapy were included in the study. Radiological and endoscopic examination of the upper gastrointestinal tract was carried out. Patients with gastric outlet obstruction were excluded. Twelve healthy and euthyroid people with no detectable gastrointestinal pathology were examined as a control group. The mean age of this group was 45 (range 35-55) years. Patients and control group received a semisolid meal containing 1 mCi technetium-99m sulphur colloid and measurements were made from the epigastrium. RESULTS: Mean gastric emptying half-time (t(half)) was 112.13+/-48.96 min in hypothyroid patients and 57.87+/-6.38 min in the control group. Gastric emptying time of the hypothyroid patients was significantly different from the control group (P< 0.001). There was no correlation between gastric emptying time and serum thyroid-stimulating hormone (TSH) levels. CONCLUSION: We concluded that radioisotopic study is a safe, rapid and reliable method for determining gastric emptying time in patients with primary hypothyroidism.

Adult↗

PubMed2003

Interstitial cells in the musculature of the gastrointestinal tract: Cajal and beyond.

Expression of the receptor tyrosine kinase KIT on cells referred to as interstitial cells of Cajal (ICC) has been instrumental during the past decade in the tremendous interest in cells in the interstitium of the smooth muscle layers of the digestive tract. ICC generate the pacemaker component (electrical slow waves of depolarization) of the smooth musculature and are involved in neurotransmission. By integration of ICC functions, substantial progress has been made in our understanding of the neuromuscular control of gastrointestinal motility, opening novel therapeutic perspectives. In this article, the ultrastructure and light microscopic morphology, as well as the functions and the development of ICC and of neighboring fibroblast-like cells (FLC), are critically reviewed. Directions for future research are considered and a unifying concept of mesenchymal cells, either KIT positive (the "ICC") or KIT negative "non-Cajal" (including the FLC and possibly also other cell types) cell types in the interstitium of the smooth musculature of the gastrointestinal tract, is proposed. Furthermore, evidence is accumulating to suggest that, as postulated by Santiago Ramon y Cajal, the concept of interstitial cells is not likely to be restricted to the gastrointestinal musculature.

Animals↗

PubMed1990

Assessment of autonomic nerve function in myotonic dystrophy.

The function of the autonomic nervous system was studied in 23 patients with myotonic dystrophy, from a defined population in northern Sweden with an extremely high prevalence of this disease. Heart rate variability tests showed only minor signs of parasympathetic dysfunction. Blood pressure and plasma noradrenaline measurements in recumbent and upright positions showed no signs of sympathetic neuropathy. Increased plasma levels of noradrenaline was an unexpected finding. Our study does not support the hypothesis that cardiac arrhythmias, orthostatic hypotension, gastrointestinal motility disturbances and urinary bladder dysfunction in myotonic dystrophy are caused by autonomic neuropathy, and we believe that these symptoms should rather be ascribed to a defective function of the target organs.

Adolescent↗

PubMed1998

Effect of moderate and heavy alcohol consumption on intestinal transit time.

BACKGROUND: Alcohol abusers frequently have gastrointestinal symptoms, such as diarrhea, nausea and vomiting. In the genesis of these symptoms multiple mechanisms are involved, including alteration of gastrointestinal motility. The aim of our study was to investigate oro-cecal transit time (OCTT) using the H2-breath test (H2-BT) in moderate and heavy drinkers. MATERIALS AND METHODS: We studied 40 chronic drinkers: 20 with heavy alcohol consumption (> or = 60 g/day for men and > or = 40 g/day for women) and 20 with moderate alcohol intake (< 60 g/day for men and < 40 g/day for women). The control group consisted of 20 teetotal subjects. All subjects underwent a lactulose H2-BT to assess OCTT. RESULTS: OCTT in heavy alcohol drinkers ranged from 100 to 240 min, with a mean of 149.5 min, while OCTT in moderate drinkers ranged from 70 to 140 min, with a mean of 109 min. In the control group the mean OCTT was 100 mins, ranging from 70 to 130 min. The difference between alcohol abusers and controls was statistically significant; on the contrary, there was no statistically significant difference between moderate alcohol drinkers and teetotallers. CONCLUSIONS: Our study shows that only in chronic heavy alcohol drinkers is OCTT clearly increased. Multiple mechanisms are hypothesized to explain motility disorder, such as visceral autonomic neuropathy, inflammation and loss of contractile proteins of smooth muscle layer of the small intestine.

Adolescent↗

PubMed2002

Gastrointestinal recovery and outcome after laparoscopy-assisted versus conventional open distal gastrectomy for early gastric cancer.

Laparoscopy-assisted gastrectomy has been increasingly reported as the treatment of choice for early gastric cancer. However, there is little information regarding the benefits of laparoscopy-assisted distal gastrectomy (LADG). LADG and conventional open distal gastrectomy (DG) for early gastric cancer were compared in terms of operative outcome, recovery of bowel function, complications, and changes in body weight. Thirty-four patients underwent LADG for early gastric cancer. These patients were compared with 31 patients who underwent DG during the same period. For estimating gastrointestinal motility recovery, 20 radiopaque markers were inserted into the duodenum during surgery, and abdominal X-rays were taken daily until all markers were seen in the ascending colon. Age, gender, and histologic differentiation of the lesions were matched. The LADG group required a significantly longer operative time and the dissection of fewer lymph nodes. Postoperative hospital stay and the occurrence of postoperative complications (ileus) were significantly shorter and less frequent in the LADG group. The LADG group showed a more rapid recovery of gastrointestinal motor function compared with the DG group during the early postoperative period. Body weight 24 months after LADG was about 100% of pre-illness weight, but no further weight change was encountered in the DG group. For selected patients with early gastric cancer, LADG with lymphadenectomy can provide a rapid recovery and good quality of life without compromising the cure rate.

Adult↗

PubMed1990

Update: pharmaceuticals and gastric emptying.

Radionuclide techniques have provided gastric emptying (GE) rate data for liquid, solid, and indigestible intraluminal contents. These data have been collected for basal states and following drug administration. Because the ability of drugs to effect GE may alter the bioavailability of orally administered medication, the latter findings are clinically useful for drugs which secondarily effect GE, as well as those whose primary objective is alteration of gastrointestinal motility. This paper reviews the current understanding of the physiology of GE, followed by an informational review of drugs listed first by medical subspecialty and then based upon special use, including antipyretics, non-narcotic analgesics, and recreational drugs.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Leptin receptor immunoreactivity in sympathetic prevertebral ganglion neurons of mouse and rat.

Prevertebral ganglia, comprising the inferior mesenteric, superior mesenteric and celiac ganglia, contain the cell bodies of sympathetic neurons that regulate gastrointestinal motility, visceral blood flow, secretion and absorption. In the present study, we report the presence of leptin receptor-like immunoreactivity in the superior mesenteric and celiac ganglia of mice and rats. Ganglion neurons were immunopositive for leptin receptor. Confocal microscopy and three-dimensional (3-D) reconstruction of ganglion neurons filled with Lucifer yellow and then immunostained for leptin receptor showed that leptin receptor immunoreactivity was intracellular and that it was present on structures encircling the nucleus. These results raise the possibility that leptin may affect gastrointestinal function by acting on leptin receptors located in prevertebral ganglion neurons.

Animals↗

PubMed2003

Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis.

Peptide hormones are secreted from endocrine cells and neurons and exert their actions through activation of G protein-coupled receptors to regulate a diverse number of physiological systems including control of energy homeostasis, gastrointestinal motility, neuroendocrine circuits, and hormone secretion. The glucagon-like peptides, GLP-1 and GLP-2 are prototype peptide hormones released from gut endocrine cells in response to nutrient ingestion that regulate not only energy absorption and disposal, but also cell proliferation and survival. GLP-1 expands islet mass by stimulating pancreatic beta-cell proliferation and induction of islet neogenesis. GLP-1 also promotes cell differentiation, from exocrine cells or immature islet progenitors, toward a more differentiated beta-cell phenotype. GLP-2 stimulates cell proliferation in the gastrointestinal mucosa, leading to expansion of the normal mucosal epithelium, or attenuation of intestinal injury in experimental models of intestinal disease. Both GLP-1 and GLP-2 exert antiapoptotic actions in vivo, resulting in preservation of beta-cell mass and gut epithelium, respectively. Furthermore, GLP-1 and GLP-2 promote direct resistance to apoptosis in cells expressing GLP-1 or GLP-2 receptors. Moreover, an increasing number of structurally related peptide hormones and neuropeptides exert cytoprotective effects through G protein-coupled receptor activation in diverse cell types. Hence, peptide hormones, as exemplified by GLP-1 and GLP-2, may prove to be useful adjunctive tools for enhancement of cell differentiation, tissue regeneration, and cytoprotection for the treatment of human disease.

Animals↗

PubMed1982

Reversal of lower esophageal sphincter hypotension and esophageal aperistalsis after treatment for hypothyroidism.

A 65-year-old woman suffered from both chronic gastroesophageal reflux, which was complicated by columnar metaplasia (Barrett's epithelium), and profound hypothyroidism. An esophageal motility tracing showed absence of peristalsis in the lower esophagus and the lower esophageal sphincter (LES) could not be identified. Thyroid replacement therapy, in conjunction with antacid and cimetidine treatment, was associated not only with improvement in the gastroesophageal reflux symptoms, but also with a return of esophageal peristalsis and LES pressure to normal. To support our clinical observations, we rendered four cats hypothyroid with 131I and documented a fall in LES pressure. We propose that abnormal smooth-muscle function of the esophagus may be another manifestation of the gastrointestinal motility disturbances which are associated with hypothyroidism.

Aged↗

PubMed1987

Barbiturate poisoning and gastrointestinal propulsion.

Anaesthetic doses of pentobarbitone (50 mg/kg) were found to inhibit gastric emptying and gastrointestinal transit in the rat. Gastric emptying was more profoundly suppressed than gastrointestinal transit. Phenobarbitone (150 mg/kg) had a similar effect. Since pentobarbitone and phenobarbitone also blocked the peristaltic reflex in the isolated small intestine of the guinea-pig, it would appear that the inhibitory effect of anaesthetic doses of barbiturates on gastrointestinal motility is mainly due to a direct action on the digestive tract. Together with the observation that considerable amounts of phenobarbitone were found in the stomach of an intoxicated patient 3 days after drug intake, these results might indicate that gastric lavage should also be considered in the treatment of protracted barbiturate poisoning.

Animals↗

PubMed1990

Day and night esophageal motor function.

Circadian rhythmic variation has been documented in gastric, small bowel and colonic motility. Morning and evening studies of esophageal motility were performed to assess whether similar rhythmicity exists in esophageal function. Fifteen healthy male subjects were studied twice on separate study days. Esophageal manometry was performed either at 10 AM or 10 PM after a standardized meal given 10 h prior to each study. Lower esophageal sphincter pressures, distal esophageal contractile amplitudes, distal esophageal contractile durations, and the velocity of propagation of peristaltic waves in the proximal and distal esophagus were measured. No significant differences were detected in esophageal function between day and night studies. These findings suggest either 1) nocturnal slowing of gastrointestinal motility is not a generalized characteristic of the entire GI tract, or 2) a two time-point study is not adequate to detect a true circadian rhythm in esophageal motor function.

Adult↗

PubMed1998

Gastrointestinal manifestations of scleroderma.

Gastrointestinal involvement is commonly found in scleroderma. Gastrointestinal symptoms may be the presenting symptoms for the diagnosis and may precede the actual diagnosis by months to years. The esophagus is the most frequently affected, but functional problems of the anorectum, small bowel, colon, and stomach may occur. The pathophysiologic mechanism appears to be one of smooth muscle atrophy and, to a lesser degree, fibrosis. These changes result in gastrointestinal motility disturbances and may cause GERD, pseudo-obstruction, bacterial overgrowth, and defecatory disorders. Malnutrition may be a serious consequence. The evaluation of a particular symptom in a patient with scleroderma may lead to treatment strategies that improve the patient's sense of well-being and quality of life.

Digestive System Diseases↗

PubMed2002

Novel N-[1-(1-substituted 4-piperidinylmethyl)-4-piperidinyl]benzamides as potent colonic prokinetic agents.

A series of novel N-[1-(1-substituted 4-piperidinylmethyl)-4-piperidinyl]benzamides was prepared and its compounds were evaluated for their binding to 5-HT(4) receptors and effects on gastrointestinal motility in conscious dogs. 4-Amino-N-[1-[1-(4-aminobutyl)-4-piperidinylmethyl]-4-piperidinyl]-5-chloro-2-methoxybenzamide (15) was found to have a potent binding affinity for 5-HT(4) receptors (IC(50): 6.47nM) and showed excellent colonic prokinetic activity.

Animals↗

PubMed1996

Identification of gastric related neurones in the rat insular cortex.

Location peculiarities of insular neurones implicated in the regulation of gastrointestinal motility have been studied in acute experiments on rats. After microinjection of a horseradish peroxidase solution in a part of the dorsal vagal complex that receive gastric afferent inputs, retrogradely labelled cell bodies are observed in a certain area of the agranular and disgranular insular cortex. Electrical stimulation of the insular cortex area had no significant effect on heart and respiration rate but had evoked gastric tone changes. These results suggest that the insular cortex contains a specific cell group that provides direct output to the bulbar 'gastric' centre and takes part in regulation of gastrointestinal functions.

Animals↗

PubMed2006

Effect of commonly used vehicles on gastrointestinal, renal, and liver function in rats.

INTRODUCTION: Solubility is often a limiting factor when testing new compounds in animal experiments. Various solubilizing agents may be used, but each have their own pharmacological effects. We investigated the effects of selected vehicles having different chemical characteristics on gastrointestinal, renal, and liver function. METHODS: Rats were treated orally, intravenously or intraperitoneally and gastric emptying, intestinal transit, renal, and liver function were investigated. RESULTS: Gastrointestinal motility was influenced by hydroxyethylcellulose, hydroxypropyl-beta-cyclodextrin (HPbetaCD), HPgammaCD, DMSO, polyethylene glycol 400 (PEG 400), fat emulsion, and the corresponding emulsifier. Liver function was affected by HPbetaCD, HPgammaCD, DMSO, PEG 400, Polysorbate 80, Cremophor RH 40, and fat emulsion. An increase in liver enzymes was observed after PEG 400 and Polysorbate 80. DMSO interfered with clinical chemistry measurements in serum. Urinary function was modified by HPgammaCD, DMSO, PEG 400, and Polysorbate 80, while enhanced urine enzyme excretion was observed after HPbetaCD, HPgammaCD, DMSO, PEG 400, and Polysorbate 80. DISCUSSION: Most of the investigated vehicles changed gastrointestinal, renal, and/or liver parameters after application of a certain threshold dose for each assay. No "best" vehicle could be identified that may be used in each test system. Thus, vehicles must be selected not only on their chemical characteristics but also on their potential pharmacological activity in a given test system.

Animals↗