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Effects of juice from Morinda citrifolia (Noni) on gastric emptying in male rats.

The effects of juice from Morinda citrifolia (noni) on gastric emptying, gastrointestinal transit, and plasma level of cholecystokinin (CCK) in rats were studied. Male rats were given noni by gavage at levels of 0.25, 1, or 4 ml/kg once per day for one or 7 days. The rats in the control group were given water, while the rats in the experimental group were fasted overnight before measurement of gastrointestinal motility. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal (10%) and Na251CrO4 (0.5 microCi/ml). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Then, gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Finally, blood samples were collected for measurement of CCK by radioimmunoassay. The administration of noni at 0.25 ml/kg, but not at 1 ml/kg and 4 ml/kg, for 1 day significantly inhibited gastric emptying. In contrast, gastric emptying was significantly inhibited by oral noni (0.25, 1, or 4 ml/kg) for 7 days. Intraperitoneal injection of lorglumide (5 or 10 mg/kg), a selective CCK1 receptor antagonist, effectively attenuated the noni-induced inhibition of gastric emptying. The intestinal transit and body weight, food intake, water intake, urine volume as well as feces weight were not altered by the administration of noni either acutely or chronically, but the administration of oral noni (1 ml/kg) for 7 days increased the level of plasma CCK in male rats. These results suggest that oral noni inhibits gastric emptying in male rats via a mechanism involving stimulation of CCK secretion and CCK1 receptor activation.

Animals↗

The possible role of the gut neuroendocrine system in diabetes gastroenteropathy.

Gastrointestinal symptoms such as nausea and vomiting, heartburn, abdominal pain, diarrhoea, constipation and faecal incontinence are common in patients with diabetes. Diabetes gastroenteropathy is a clinically relevant problem. In addition to the increased morbidity it causes, it results in severely impaired metabolic control, which in turn increases the risk of hyper-/hypoglycaemia. Moreover, the poorly controlled blood glucose level increases the risk of secondary diabetes complications, namely, retinopathy, nephropathy, neuropathy and cardiovascular affection. Gastrointestinal symptoms may also cause malnutrition in patients with diabetes, which, together with the disturbed immune defence in diabetes, may cause intercurrent infections. Gastrointestinal symptoms in patients with diabetes are attributed to disturbed gastrointestinal motility. Gastrointestinal dysmotility in diabetes is believed to be caused by autonomic neuropathy and/or hyperglycaemia. The neuroendocrine system of the gut secretes peptides/amines that play an important role in regulating gastrointestinal motility. It is conceivable, therefore, to assume that a disturbance in this regulatory system may contribute to the pathogenesis of gastrointestinal complications in diabetes. The present review gives an updated overview of the abnormalities in the gastrointestinal neuroendocrine system in diabetes, speculates upon the possible role of these abnormalities in the pathogenesis of diabetes gastroenteropathy and, finally, predicts the possible clinical implications of these findings.

Animals↗

From the bench to the 'crib'-side: implications of scientific advances to paediatric neurogastroenterology and motility.

Paediatric gastrointestinal motility disorders may present in the neonatal period as the result of a congenital insult that occurred during embryonic development or as a manifestation of an abnormal genetic background. Functional gastrointestinal and motility disorders may also be acquired and present during childhood as the first presentation of a condition that can persist or re-occur throughout adolescence and adulthood. These disorders can have a significant psychological and financial impact on the lives of the affected children and their families. Recently, enteric neuroscience research has advanced the understanding of the pathogenesis and treatment of uncommon congenital or developmental gastrointestinal motility disorders such as Hirschsprung disease and chronic intestinal pseudo-obstruction. In addition, research has contributed to improvements in the understanding of more prevalent functional gastrointestinal disorders in children, such as chronic constipation and functional abdominal pain syndromes. The purpose of this review is to highlight these advances with particular regard to the clinical impact they have in the understanding and management of disorders in the field of paediatric neurogastroenterology and motility.

Animals↗

The evaluation of the role of CCK in the opioid modulation of the motility of the gastrointestinal tract in sheep.

The participation of central cholecystokinin-8 (CCK-8) receptors in the modulatory effect of D-Ala2, N-Me-Phe4, Gly5-ol enkephalin (DAGO), a selective mu-opioid receptor agonist, on the spike burst activity of the gastrointestinal tract (rumen, reticulum, antrum, duodenum, colon and caecum) in sheep was investigated. DAGO was infused intracerebroventricularly (i.c.v.) at doses of 0.1-1 microg/kg body weight (BW). It was shown that DAGO significantly inhibited myoelectrical activity of the wall of the forestomachs, abomasum and colon but stimulated this activity in the duodenum (rate of myoelectrical migrant complex-MMC). The effects of DAGO were prevented by CCK-8 antagonists (L-364.718 and L-365.260) previously infused at doses of 5-20 microg/kg BW. The results of this present study indicate that central receptors of CCK-8 participated in the modulatory action of an opioid on myoelectrical activity of the gastrointestinal tract in sheep. Furthermore, this result suggests that CCK-8 is released in response to mu-receptor stimulation, because CCK-8 antagonists (L-364.718 and L-365.260) prevented the modulatory action of DAGO on the gastrointestinal motility in sheep.

Animals↗

Prolonged ambulatory canine colonic motility.

Canine gastrointestinal motility is studied at present in animals confined to a small cage or sling. The aims of this study were to record colonic activity over a 24-h period in eight dogs by an ambulatory method. Motility signals from implanted strain gauges were processed and stored via a portable battery-operated amplifier and digital recorder housed in a jacket. Ambulant interdigestive activity was the same as observed in laboratory experiments, with migrating colonic motor complexes (CMCs) and infrequent giant contractions (GCs). Feeding caused a multiphasic alteration in motility for 582.1 +/- 18.1 min (mean +/- SE). There were four distinct phases. During the "early" (0-2 h) postprandial period, phase 1 (mean duration: 55.1 +/- 4.0 min), which was distinguished by CMCs of high frequency and elevated amplitude in the proximal colon, and phase 2 (78.2 +/- 6.2 min), which had CMC characteristics similar to those in the interdigestive period, occurred. Phase 3 (218.8 +/- 13.6 min), a further period of increased motility, and phase 4 (339.1 +/- 14.0 min), characterized by low-amplitude long-duration CMCs, occurred during the "late" (2 h onward) postprandial response. With the exception of phase 3, postprandial phases were not always present following food intake, and their expression was markedly influenced by variations in meal time and by defecation immediately following feeding. Spontaneous defecation was characterized by a variety of motor profiles, with a GC accompanying two-thirds of episodes. We conclude that a more complete picture of canine colonic motility has been documented because of the development of the ambulatory system.

Animals↗

[Interdigestive motility and secretion of the gastrointestinal tract].

In the fasting state, the digestive tract is not inactive but displays periodic motor and secretory activity. Each gastrointestinal motility cycle can be divided into specific phases of activity: a period of inactivity (phase I), followed by a longer period of irregular activity (phase II) and by a brief, conclusive period (phase III) of maximal, rhythmic contractions, the migrating motor complex (MMC), which migrates from the gastroduodenal region to the distal small bowel within one motility cycle. A short, inconstant transition segment between phases III and I is termed phase IV. Lower esophageal, gallbladder and sphincter of Oddi motilities are also linked to this functional cycle. In contrast, colonic motility follows independent patterns. Closely correlated to upper gastrointestinal motility are secretory activities: Output rates of gastric, pancreatic and bile secretions increase and decrease periodically, in concert with upper gastrointestinal motor activities. The physiologic role of periodic interdigestive activity is not fully understood. It is probably important for regular mechanical and enzymatic cleansing ot the gastrointestinal lumen and may serve to remove indigestible and/or foreign material, to prevent bacterial overgrowth or pathologic activation of pancreatic enzymes, and to revert duodeno-gastric and ceco-ileal refluxes. Control of the interdigestive cycle and mechanisms of motor/secretory coupling have been only partly uncovered; however, recent findings suggest that interactions between vagal and intrinsic cholinergic pathways and gastrointestinal hormones may play pivotal regulatory roles.

Digestion↗

Georges Brohee Prize 1994. Motilin and the enteric nervous system in the control of interdigestive and postprandial gastric motility.

The upper gastrointestinal tract displays two different functional states: the interdigestive or fasting state, and the fed state. The fasting state is characterized by a cyclical motor pattern, the migrating motor complex (MMC). The control of the MMC is incompletely understood. Plasma levels of the hormone motilin fluctuate in synchrony with MMC, but it is still controversial whether a motilin peak triggers the MMC or whether the MMC causes motilin release. We used the motilin agonistic properties of erythromycin to resolve this issue in man. Administration of a low dose of erythromycin induced a MMC which started from the gastric antrum, unaccompanied by a motilin peak. This finding argues against a release of motilin secondary to the MMC and supports our hypothesis that in man motilin peaks trigger the MMC. We observed that higher doses of erythromycin no longer induced a MMC, but stimulated antral contractility. The enteric nervous system is involved in the control of both the fasting and fed state at each level of the gastrointestinal tract. We hypothesized that the target for motilin to trigger the MMC is the enteric nervous system in the gastric antrum. Yet, no physiological data on antral enteric neurons were available. We performed the first electrophysiological study of myenteric neurons of the gastric antrum, revealing unique electrical and synaptic properties in comparison to other regions of the gastrointestinal tract. We confirmed the role of the enteric nervous system of the gastric antrum in the control of the MMC by directly demonstrating the presence of motilin receptors on a subpopulation of neurons. We demonstrated that endogenous and exogenous substances that stimulate (cholecystokinin, cisapride, erythromycin) or inhibit (norepinephrine, 5-hydroxytryptamine) gastric emptying all act on antral enteric neurons. These observations strongly support the hypothesis that the enteric nervous system in the gastric antrum plays a key role in the coordination of antral peristalsis and the regulation of gastric emptying. Finally, we hypothesized that the actions of erythromycin on motilin receptors on enteric neurons and intestinal smooth muscle offer a potential for therapeutic applications in gastrointestinal motility disorders. We confirmed this by demonstrating gastrointestinal motility stimulating activity of erythromycin in patients with diabetic gastroparesis.

Animals↗

Cholecystokinin, secretin, pancreatic polypeptide in relation to gallbladder dynamics and gastrointestinal interdigestive motility.

Using a combined technique of hepatobiliary scintigraphy and gastrointestinal motility recordings, the changes in blood concentrations of cholecystokinin (CCK), secretin and pancreatic polypeptide (PP) were studied in relation to gastrointestinal motility and gallbladder dynamics in the interdigestive state in 7 healthy male volunteers. No changes in CCK concentration were found in relation to the migrating motor complex (MMC). In 3 subjects a slightly but insignificant elevated secretin level was seen during phase I of the MMC, otherwise no changes were observed. More pronounced fluctuations in PP appeared with significantly higher values during phase III compared to phase II. Values of concentrations of CCK, secretin and PP in periods with gallbladder filling were not significantly different from the values in periods of emptying.

Adult↗

Autonomic dysfunction in chronic intestinal pseudo-obstruction.

Fifteen tests were used to assess adrenergic, non-vagal cholinergic, and cardiovagal functions in 11 patients with chronic intestinal pseudo-obstruction (CIP). The three aims of this study were: 1) to ascertain the presence of and spectrum of autonomic involvement; 2) to assess the level of autonomic dysfunction; and 3) to compare the results of autonomic function tests with gastrointestinal motility patterns. Gastrointestinal motility displayed a neuropathic pattern in 10 patients. Adrenergic functions were abnormal in nine patients and non-vagal cholinergic functions in 10 patients. Cardiovagal functions were abnormal in only seven patients. The autonomic dysfunction was localized mostly to the postganglionic pathways. One patient, who had a myopathic pattern and muscle degeneration on small bowel biopsy, demonstrated normal responses to autonomic function tests. The patients with neuropathic CIP demonstrated widespread, mostly postganglionic autonomic dysfunction. Neuropathic CIP can occur with or without cardiovagal involvement.

Acetylcholine↗

Motility disorders of the gastrointestinal tract.

Over the past decades our knowledge of normal and abnormal gastrointestinal motility has increased tremendously. The availability of manometry to study bowel contraction patterns, laparoscopy to perform full thickness bowel biopsies for histological examination, have added to the investigative armamentarium and helped better diagnose motility disorders. However, the development of newer therapies for bowel motility disorders has been disappointingly slow. Newer modalities such as gastric and bowel pacing provides some hope for the future. In this article we have provided an overview of some of the common motility disorders in children and discussed their management.

Anal Canal↗

[Effects of smoking on motility of the upper gastrointestinal tract in healthy persons and patients with peptic ulcer].

59 male volunteers (16 healthy and 43 ulcer subjects) entered the study on effects of smoking on gastrointestinal motility. The latter was assessed within 12-50 hours by means of probes fitted with tensiometers. Smokers, especially heavy smokers, regardless of the disease presence, had more regular phase alterations in the cycles of the motility and more regular rhythm of phase III, more frequent involvement of the stomach in frontal motor activity. A direct effect of the cigarette smoked on gastric and intestinal motility was associated with condition of the patient and time after meal.

Adolescent↗

Effects of trout endothelin on the motility of gastrointestinal smooth muscle from the trout and rat.

Trout endothelin (ET), previously isolated from the kidney of the rainbow trout Oncorhynchus mykiss, contains four amino acid substitutions at residues 4-7 compared with rat ET-1. Trout ET produced sustained and concentration-dependent contractions of strips of longitudinal smooth muscle from trout stomach (pD(2) = 7.52 +/- 0.06) and proximal small intestine (pD(2) = 7.80 +/- 0.10) and from rat fundus (pD(2) = 7.78 +/- 0.14). Rat ET-1 was equipotent with trout ET for contraction of rat fundus and 2- to 3-fold more potent for contraction of trout gastrointestinal tissues. In contrast, rat ET-1 was 10- to 20-fold more potent than trout ET in constricting isolated rings of vascular tissue from trout efferent branchial artery and cardinal vein and from rat aorta (Y. Wang et al., 1999, Am. J. Physiol. 277, R1605-R1611). It is known that the contractile effects of ET-1 on rat fundus are mediated through the ET(B) receptor and effects on the rat aorta are mediated through the ET(A) receptor. We propose, therefore, that trout gastrointestinal tissues express an ET(B)-type receptor that differentiates poorly between trout ET and rat ET-1, whereas trout vascular tissues express an ET(A)-type receptor that is preferentially activated by rat ET-1. The rat ET-1-induced contractions of the trout gastrointestinal tissues are in part indirect, involving a serotoninergic neuronal pathway in the intestine and a noncholinergic, nonserotoninergic pathway in the stomach.

Animals↗

[Effects of intracerebroventricular injections of thyrotropin releasing hormone on gastrointestinal propulsive motility in rats].

The effect of intracerebroventricular (ICV) injections of thyrotropin releasing hormone (TRH) on the propulsive motility of the gastrointestinal tract was examined in rats. The distance travelled by charcoal meal through the small intestine, measured in terms of percentage of its total length, was recorded as the index of propulsive motility. The results were as follows: (1) The propulsive distance of charcoal meal was significantly reduced in a dose-dependent manner after ICV injections of TRH (1 microgram/10 microliters, 5 micrograms/10 microliters or 10 micrograms/10 microliters) (P less than 0.01-0.001) The effects were abolished by injection of atropine (5 micrograms/10 microliters ICV). (2) The gastrointestinal propulsive motility decreased markedly (P less than 0.01) after injection of a larger dose of TRH (50 micrograms/100 g) into the hypodermis. The effects were not completely blocked by subcutaneous injections of propranolol (5 mg/kg). (3) No effects (P greater than 0.05) were found on the inhibition of gastrointestinal propulsive motility after ICV injections of regitine (2.5 mg/kg im, 50 micrograms/50 microliters ICV) or propranolol (5 mg/kg im, 50 micrograms/50 microliters ICV). The results indicate that TRH has an inhibitory effect on the propulsive motility of gastrointestinal tract, which may be mediated via the non-adrenergic inhibitory nerve of the vagal nerves.

Animals↗

Motility and hemodynamics of the canine gastrointestinal tract. Stimulation by pentagastrin, cholecystokinin and vasopressin.

Effects of pentagastrin (1-4096 ng/kg), cholecystokinin (1-4096 mU/kg, CCK) and vasopressin (.032-128 mU/kg) on gastrointestinal motility and blood flow, were determined by simultaneous measurement of blood flow (electromagnetic flow probes) to and motor activity (strain gages) of corpus, antrum, duodenum, jejunum, and colon of anesthetized dogs. Antral contractile amplitude was increased by pentagastrin at relatively low doses. Pentagastrin also increased corpus blood flow, corpus tone and antral blood flow. Gastric contractile frequency was least sensitive to pentagastrin. Corpus blood flow was decreased and small intestinal blood flow was increased by cholecystokinin at relatively low doses. CCK also increased small intestinal contractile amplitude and, at higher doses, antral contractile amplitude, and duodenal tone. Time-effect relation and sensitivity were different for the hemodynamic and motor responses to pentagastrin and to cholecystokinin. This shows the lack of correlation between vasoactive and motor-stimulating properties of these drugs. However, strong drug-induced contractions were shown to impede antral blood flow (pentagastrin and CCK) by about 35% and duodenal and jejunal blood flow (CCK) by resp. 70 and 60%. Vasopressin reduced blood flow to stomach and intestines by 50-80%, without affecting gastrointestinal motility.

Animals↗

Review article: gall-bladder motility after intestinal surgery.

There is a close relationship in humans between gall-bladder motility and gastrointestinal motility during the fasting state, as well as in the post-prandial period. Only a minority of publications take this relationship into account in the description of biliary dysmotility after various surgical procedures. Most publications deal with post-prandial gall-bladder motility or with stimulation of gall-bladder contraction from various prokinetic drugs or gastrointestinal hormones. Impaired gall-bladder motility has been demonstrated after Billroth II gastric resection, pyloroplasty and colectomy, but the epidemiological data on the risk of gallstone formation in these patients are too scarce and equivocal to recommend prophylactic cholecystectomy. Future studies on gall-bladder motility after surgical procedures should include measurements of gall-bladder motility during the fasting state, as well as in the post-prandial period. The measurements should be related to the migrating motor complexes, and this necessitates a simultaneous recording of gastrointestinal motility.

Cholelithiasis↗

Erythromycin for feeding intolerance in preterm infants.

BACKGROUND: Functional immaturity of gastointestinal motility predisposes preterm infants to feeding intolerance. Motilin, a gastrointestinal peptide, stimulates propagative contractile activity during phase III of the migratory motor complex in the interdigestive state. Erythromycin (EM) is a motilin agonist with prokinetic effect at low doses (1-3mg/kg). OBJECTIVES: To evaluate the effectiveness of EM in promoting gastrointestinal motility in preterm infants with feeding intolerance and assess clinically significant adverse effects associated with its use. SEARCH STRATEGY: Systematic literature search in accordance with the Cochrane Neonatal Collaborative Review Group search strategy. Randomized and quasi-randomized controlled trials of EM use, at any dose, in preterm infants to promote gastrointestinal motility were identified by searching MEDLINE, EMBASE, CINAHL, the Cochrane Library, reference lists of published studies, personal files, and abstracts published in Pediatric Research. SELECTION CRITERIA: Randomized controlled trials of oral or intravenous EM use at dose range of 3 to 12 mg/kg/day in preterm infants less than or equal to 36 weeks gestational age with feeding tolerance were included in this review. DATA COLLECTION AND ANALYSIS: Data regarding the primary clinical outcome of days to achieve full enteral feeding were compared among studies. Data on secondary outcomes including adverse effects associated with the use of EM (diarrhea, nosocomial infections, cardiac arrhythmias, or theophylline toxicity), duration of parenteral nutrition, weight gain, incidence of necrotizing enterocolitis (NEC), hypertrophic pyloric stenosis, and length of hospital stay were assessed. MAIN RESULTS: Two randomized controlled studies of EM use in preterm infants for improving gastrointestinal motility were identified. Since both studies involved preterm infants treated with EM at dose >12mg/kg/day at commencement of feeding, they did not meet inclusion criteria defined a priori for this review. There was no statistically significant difference in the incidence of NEC (RR 0.59, 95%CI 0.11, 3.01; RD -0.021, 95%CI -0. 087, 0.045). No statistically significant difference was noted in days to achieve full enteral feeds, length of hospital stay, and adverse events between groups. REVIEWER'S CONCLUSIONS: EM at antimicrobial doses may not be effective in preterm infants with feeding intolerance. Further studies are needed to determine whether EM in lower doses is effective as a prokinetic agent in such infants.

Anti-Bacterial Agents↗

[Intestinal pseudo-obstruction].

Intestinal pseudo-obstruction is a rare and heterogeneous syndrome caused by severe disorders of gastrointestinal motility. It affects the entire gastrointestinal tract or only segments, giving rise to symptoms and physical signs of a mechanical obstruction of the gut despite negative results of all imaging procedures. The disease may occur in an acute or chronic form. The acute and some of the chronic forms develop as complication of other gastrointestinal or extragastrointestinal diseases, e.g. pancreatitis or systemic sclerosis. The primary forms of chronic intestinal pseudo-obstruction are most often caused by genetic neuromuscular disorders of the gastrointestinal tract, e.g. familial visceral neuropathies. The diagnosis of intestinal pseudo-obstruction is based on the exclusion of a mechanical obstruction of the gut by fluoroscopy and endoscopy. Manometric studies may disclose the underlying disorder of gastrointestinal motility. In a few patients, results of all imaging procedures as well as motility studies are inconclusive, and laparatomy (with full thickness biopsy of the gut wall) has to be performed to exclude mechanical obstruction of the gut. Acute intestinal pseudo-obstruction is treated by elimination of the underlying intestinal or extraintestinal disease. In case of extensive colonic dilatation with imminent colonic perforation endoscopic decompression should be evaluated. Treatment of chronic pseudo-obstruction aims to correct the underlying motility disorder. Usually, restoration of normal gastrointestinal motility is attempted by prokinetic drugs, but often their effect is limited. Surgery may be helpful in the few patients in whom the disease is confined to small segments of the gut, leaving all other parts unaffected. Some patients with otherwise intractable disease may need long-term parenteral nutrition.

Acute Disease↗

Diagnosing motility disorders of the upper gastrointestinal tract.

The past decade has witnessed an exponential growth of knowledge about upper gastrointestinal motility. The elucidation of the clinical problems is based on remarkable morphophysiologic, clinical, diagnostic, and pharmacotherapeutic advances. New approaches rely on a more sensitive application of manometric evaluation which has allowed identification of more subtle abnormalities of motility, as well as appreciation of the role of scintigraphic studies to measure transit through the esophagus, combined with the standard use of the cine-esophagogram modified to assess a solid bolus. New techniques to evaluate gastric motility include myoelectric gastrography and administration of isotope-labeled meals. These advances have been enhanced by the advent of prokinetic therapeutic agents, such as metoclopramide and domperidone. Evaluation of intestinal motility involves the use of intraluminal pressure sensing catheters, as well as methods to measure transit times. The standard hydrogen breath test as a noninvasive study of small intestinal transit time has been supplemented by an isotope-labeled liquid meal. Identification of clinical states with delayed and rapid small bowel transit times will have therapeutic implications in the future.

Breath Tests↗