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PubMed2002

Prolonged gastrointestinal transit in a patient with a glucagon-like peptide (GLP)-1- and -2-producing neuroendocrine tumor.

Neuroendocrine tumors overexpressing the proglucagon- derived peptides have been associated with severe constipation. The relationship between two of the intestinal proglucagon-derived peptides, glucagon-like peptide (GLP)-1 and -2, and delayed gastrointestinal transit, was characterized in a patient with a neuroendocrine proglucagon-derived peptide tumor. A 60-yr-old female presented with intractable constipation and intermittent vomiting. Gastric, oral-ileal and colonic transit times, and plasma hormone levels were determined before tumor resection. Expression of the proglucagon-derived peptides by the tumor was determined by immunohistochemistry, Northern blot analysis, HPLC, and RIA. Oral-cecal transit was more than 3 h, and a barium follow-through study showed dilated and thickened folds with most of the barium concentrated in the ileum at 24 h; residual barium was identified in the colon at 14 d post ingestion. Circulating levels of GLP-1 and -2 were 300- to 400-fold elevated compared with levels in normal human subjects. Normal bowel function was restored by tumor resection. Consistent with the elevated plasma hormone levels, the tumor was found to express the proglucagon gene, and immunoreactive GLP-1 and -2 were detected by both immunohistochemistry and RIA. Overexpression of glucagon-like peptide-1 and -2 is associated with markedly prolonged gastrointestinal transit in humans. These findings are consistent with a role for these peptides in the regulation of gastrointestinal motility.

Female↗
PubMed1981

Myoelectric control of gastrointestinal and biliary motility: a review.

The movement of ingested food and secretions through the gastrointestinal and its appendages depends on a highly integrated and coordinated response of the smooth muscle contained within the wall of the gut. This review will consider, in detail, the various myogenic factors that contribute to the usual aboral propulsion of the gastrointestinal contents. The role of myoelectrical complexes as represented by slow waves and spike potentials are emphasized, for they appear to play a central role in the initiation of sphincter function and gastrointestinal peristalsis. The myoelectric control of the sphincter of Oddi is discussed in relationship to gastroduodenal motility, since disturbances in this finely modulated sphincter may lead to biliary-pancreatic dysfunction and symptoms of upper gastrointestinal disease.

Animals↗
PubMed2003

Systematic review: serotonergic modulators in the treatment of irritable bowel syndrome--influence on psychiatric and gastrointestinal symptoms.

BACKGROUND: Both central and peripheral serotonergic modulators are used in the treatment of irritable bowel syndrome. The majority of patients with irritable bowel syndrome presenting to a gastroenterologist demonstrate affective dysregulation. Serotonin may play a regulatory role in both gastrointestinal motility and sensitivity, as well as in affective dysregulation, in irritable bowel syndrome. AIM: To analyse, systematically, randomized controlled trials studying the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome, in order to elucidate baseline irritable bowel syndrome symptomatology and possible differential effects of serotonergic modulation on this symptomatology. METHODS: A standardized qualitative analysis was performed of studies investigating the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome using a blind review approach. The studies were ranked according to their total quality score (maximum 100 points). RESULTS: Eleven studies fulfilled the entry criteria, six of which scored above 55 points. An association between gastroenterological and psychiatric changes was present in five of the six studies. CONCLUSIONS: The results strengthen the serotonergic association between gastroenterological and psychiatric symptoms. Adjusted guidelines for combined gastrointestinal and psychiatric assessments are recommended in order to further elucidate the serotonergic interaction between gastrointestinal and psychiatric symptoms.

Colonic Diseases, Functional↗
PubMed1991

Gastrointestinal manifestations of type 1 neurofibromatosis (von Recklinghausen's disease).

Gastrointestinal involvement in von Recklinghausen's disease occurs in three principal forms: hyperplasia of the submucosal and myenteric nerve plexuses and mucosal ganglioneuromatosis which leads to disordered gut motility; gastrointestinal stromal tumours showing varying degrees of neural or smooth muscle differentiation; and a distinctive glandular, somatostatin-rich carcinoid of the periampullary region of the duodenum that contains psammoma bodies and which may be associated with phaeochromocytoma. This review describes the histopathological features of these lesions and discusses potential pitfalls in their differential diagnosis. Their accurate identification has significant implications for clinical management and may even provide the first pointer to the diagnosis of neurofibromatosis.

Gastrointestinal Diseases↗
PubMed2004

Enteric P2X receptors as potential targets for drug treatment of the irritable bowel syndrome.

The irritable bowel syndrome (IBS) is a gastrointestinal motility disorder affecting millions of patients. IBS symptoms include diarrhea, constipation and pain. The etiology of IBS is due partly to changes in the function of nerves supplying the gastrointestinal tract, immune system activation and to psychological factors. P2X receptors are multimeric ATP-gated cation channels expressed by neuronal and non-neuronal cells. Sensory nerve endings in the gastrointestinal tract express P2X receptors. ATP released from gastrointestinal cells activates P2X receptors on sensory nerve endings to stimulate motor reflexes and to transmit nociceptive signals. Antagonists acting at P2X receptors on sensory nerves could attenuate abdominal pain in IBS patients. Primary afferent neurons intrinsic to the gut, and enteric motor- and interneurons express P2X receptors. These neurons participate in motor reflexes. Agonists acting at enteric P2X receptors may enhance gastrointestinal propulsion and secretion, and these drugs could be useful for treating constipation-predominant IBS. Antagonists acting at enteric P2X receptors would decrease propulsion and secretion and they might be useful for treating diarrhea-predominant IBS. Current knowledge of P2X receptor distribution and function in the gut of laboratory animals provides a rational basis for further exploration of the therapeutic potential for drugs acting at P2X receptors in IBS patients. However, more information about P2X receptor distribution and function in the human gastrointestinal tract is needed. Data on the distribution and function of P2X receptors on gastrointestinal immune cells would also provide insights into the therapeutic potential of P2X receptor agents in IBS.

Animals↗
PubMed2001

Inhibition of gastric emptying and small intestinal transit by ethanol is mediated by capsaicin-sensitive afferent nerves.

The neural mechanisms involved in mediation of the inhibitory effects of ethanol on the gastric emptying and the small intestinal transit were studied in adult male rats. The gastrointestinal transit was determined by measuring the amount of phenol red recovered from the stomach and small intestine after intragastric administration. Spinal and/or vagal peptidergic afferent nerves were subjected to selective denervation by chemodenervation techniques using capsaicin, a potent and specific sensory neurotoxin. Intragastric administration of a 2.5 g/kg body weight dose of ethanol resulted in inhibition of the gastric emptying and the small intestinal transit. Prior systemic treatment with capsaicin, which defunctionalizes both spinal and vagal capsaicin-sensitive afferent nerves, abolished the inhibitory effect of ethanol on the gastrointestinal transit. Similarly, selective chemodenervation of the vagal afferents by perineural capsaicin treatment completely blocked the effect of ethanol. These observations furnish evidence indicative of the involvement of capsaicin-sensitive neural pathways, and in particular vagal afferent nerves, in the mediation of the inhibitory effect of large doses of ethanol on the gastrointestinal motility.

Animals↗
PubMed2001

Potential benefits and hazards of physical activity and exercise on the gastrointestinal tract.

This review describes the current state of knowledge on the hazards of exercise and the potential benefits of physical activity on the gastrointestinal tract. In particular, acute strenuous exercise may provoke gastrointestinal symptoms such as heartburn or diarrhoea. A substantial part (20-50%) of endurance athletes are hampered by these symptoms which may deter them from participation in training and competitive events. Nevertheless, these acute symptoms are transient and do not hamper the athlete's health in the long term. The only exception is repeated gastrointestinal bleeding during training and competition, which in the long term may occasionally lead to iron deficiency and anaemia. In contrast, repetitive exercise periods at a relatively low intensity may have protective effects on the gastrointestinal tract. There is strong evidence that physical activity reduces the risk of colon cancer by up to 50%. Less convincing evidence exists for cholelithiasis and constipation. Physical activity may reduce the risk of diverticulosis, gastrointestinal haemorrhage, and inflammatory bowel disease although this cannot be substantiated firmly. Up to now, underlying mechanisms are poorly understood although decreased gastrointestinal blood flow, neuro-immuno-endocrine alterations, increased gastrointestinal motility, and mechanical bouncing during exercise are postulated. Future research on exercise associated digestive processes should give more insight into the relationship between physical activity and the function of the gastrointestinal tract.

Digestive System Physiological Phenomena↗
PubMed2003

Sequence, distribution and quantification of the motilin precursor in the cat.

Due to motilin's relation to the migrating motor complex (MMC), the physiology of motilin has been mostly studied in man and dog. The cat does not have an MMC pattern, and little is known about cat motilin. Therefore we identified the cat motilin precursor (GenBank accession no. AF127917) and developed a quantitative polymerase chain reaction (PCR) to explore its distribution in the gastrointestinal tract and in the central nervous system (CNS). The precursor is closely related to the dog precursor and consists of an open reading frame of 348bp encoding the signal peptide (25 amino acids), the motilin sequence (22 amino acids) and the motilin associated peptide (69 amino acids). One amino acid of the signal peptide was subject to gene polymorphism. Quantification of motilin messenger RNA (mRNA) was for the first time achieved. It is most abundant in the gastrointestinal tract, with the highest concentration in the duodenum, the lowest in the colon and is not detectable in the corpus. However an important expression was also observed in several regions of the CNS, except the striatum and cerebral cortex. The highest level was in the hypothalamus (although 23-fold lower than in the duodenum), the lowest level in the pons. Moderate levels were found in the thyroid. These data suggest that the physiological role of motilin may extend beyond its effect on gastrointestinal motility.

Amino Acid Sequence↗
PubMed1983

Assessment of gastric motility using meal labeled with technetium-99m sulfur colloid.

During a 2 year period, 83 patients with gastric motility problems were evaluated using radionuclide imaging. The patients presented with epigastric distress, postprandial fullness, pain, nausea, vomiting, and diarrhea; signs and symptoms suggestive of either gastroparesis or gastric outlet obstruction. Upper gastrointestinal series or endoscopy, or both, demonstrated no mechanical obstruction. After oral administration of a 300 g meal labeled with 600 muCi of technetium-99m sulfur colloid, a gastric emptying study consisting of serial images and data acquisition was performed. Of the patients studied, 52 had had peptic ulcer surgery, 17 were suspected of having gastroesophageal reflux, 8 were diabetic and suspected of having visceral enteropathy, and 6 had a history of irritable bowel syndrome. The normal mean gastric half emptying time was 77 +/- 16 minutes. Of the patients who had had gastric surgery, 90.4 percent had abnormal emptying: 69.2 percent had delayed gastric emptying and 21.2 percent had rapid gastric emptying time; 9.6 percent had normal emptying time. Of the gastroesophageal reflux group, all but two had normal gastric emptying time; 65 percent demonstrated gastroesophageal reflux within 15 minutes. Two of the patients with irritable bowel syndrome had prolonged emptying; the rest had normal emptying. All diabetic patients with gastroparesis had prolonged gastric emptying time, and all responded favorably to metoclopramide. Of the patients who previously had peptic ulcer surgery and had prolonged emptying time, 72 percent also responded favorably to metoclopramide. We conclude that radionuclide gastric imaging is a useful diagnostic test for the measurement of gastric emptying in patients with a variety of gastrointestinal motility disorders and may be helpful in assessing medical therapy and selecting those who may be candidates for surgery.

Food↗
PubMedDate not supplied

Radiopaque markers to evaluate gastric emptying and small intestinal transit time in healthy cats.

Determinations of gastric emptying time (GET) and small intestinal transit time (SITT) are useful in detecting gastrointestinal motility disorders and partial obstructions of the pylorus or small intestine. Barium-impregnated, polyethylene radiopaque spheres with diameters of 1.5 mm and 5.0 mm have been developed for quantitative assessment of gastrointestinal transit. The purpose of this study was to evaluate GET and SITT using these radiopaque spheres in 10 healthy cats. The cats were randomly assigned to 1 of 3 treatment groups: fasted, fed, and fed plus sedation (acetylpromazine maleate 0.10 mg/kg subcutaneously). A repeated measures study design was used. The mean GETs of 50%, 75%, and 90% of the 1.5-mm and the 5-mm spheres in the unfed cats were 0.36, 0.58, and 0.74 hours, and 0.41, 0.68, and 1.02 hours, respectively. These values were significantly (P < or = .05) more rapid than the GETs of 50%, 75%, and 90% of the 1.5-mm and 5-mm spheres of either the sedated fed cats (4.39, 5.68, 6.65 and 5.15, 5.99, 6.91 hours) or the unsedated fed cats (6.43, 8.12, 9.06 and 7.49, 8.49, 9.22 hours). The mean GETs of 50% and 75% of the 1.5-mm and 5-mm and of 90% of the 1.5-mm spheres were significantly (P < or = .05) more rapid in sedated than in unsedated fed cats. The GET of 50% of the 1.5-mm spheres was significantly more rapid (P < or = .05) than that of the 5-mm spheres in the fed cats. The mean SITTs, which ranged from 2.25 to 3.05 hours, were not significantly different (P > .05) among the treatment groups or between the 1.5-mm and 5-mm spheres. The GET of spheres given to fasted cats is significantly more rapid than that of fed cats. Subcutaneous injection of acetylpromazine speeds GET in fed cats. The SITT of small and large spheres was not influenced by feeding or by acetylpromazine injection.

Animals↗
PubMed2006

Central and local (enteric) action of orexins.

Orexin-A (OXA, hypocretin-1) and orexin-B (OXB, hypocretin-2) are peptides derived from the same 130 amino acid long precursor (prepro-orexin) that bind and activate two closely related orphan G protein-coupled receptors. Orexins and their receptors were first discovered in the rat brain, and soon after that in peripheral neural structures, including the vagal nerve and enteric nervous system, and in other structures involving the gastrointestinal tract diffuse neuroendocrine system, pancreas tissue, stomach and intestinal mucosa. Orexins and their receptors were also demonstrated in the testes, adrenals, kidneys, and placenta. This review is focused on central and enteric actions. Originally, orexins were considered to be neurotransmitters that centrally stimulate food intake in animals and humans, but it soon became evident that their action is broader due to activation of a large number of neuronal pathways involved in energy homeostasis, sleep-awake behavior, nociception reward seeking, food and drug addiction, as well as reproduction, cardiovascular and adrenal function. In the gastrointestinal tract, orexins have been found so far to affect gastrointestinal motility and gastric, intestinal and pancreatic secretions. The effects were observed following central (intraventricular) or local (intraluminal, intraarterial), but not peripheral (intravenous), administrations of orexins. Since the expression of orexins in the gastrointestinal tract is enhanced during fasting, and fasting reveals many of the orexin gastrointestinal effects, it seems probable that on the local level, orexins keep the gastrointestinal tract functions ready during fasting and play role in brain-gut axis control.

Amino Acid Sequence↗
PubMed2005

AC biosusceptometry in the study of drug delivery.

Conventionally, pharmaceutical substances are administered orally because the gastrointestinal tract possesses the appropriate features for drug absorption. Nevertheless, the gastrointestinal tract physiology is complex and influenced by many factors. These factors must be completely understood for the optimization of oral drug delivery systems. Although in vitro tests provide information about release and drug absorption profiles, in vivo studies are essential, due to the biological variability. Several techniques have been employed in an attempt to conveniently characterize the behavior of solid dosage forms in vivo. The noninvasive biomagnetic technique of alternate current biosusceptometry (ACB) has been used in studies focusing on gastrointestinal motility and, more recently, to evaluate the performance of magnetic dosage forms. This article will discuss the main characteristics of AC biosusceptometry and its applicability for determination of the relationship between the human gastrointestinal tract and orally administered pharmaceutical dosage forms.

Drug Delivery Systems↗
PubMed1995

Effects of sex steroid hormones on gastric emptying and gastrointestinal transit in rats.

In vitro studies have shown that estrogen and progesterone can affect the contractile response and myoelectric activity of the gastrointestinal smooth muscle. The present study was designed to investigate the effect of sex steroid hormones on gastric emptying and gastrointestinal transit were assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and 51Cr. Gastric emptying was determined by measuring the amount of labeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating both the geometric center of distribution of the radiolabeled marker and the charcoal transit in the intestine. The experimental animals included diestrus rats; ovariectomized rats treated with vehicle, estradiol, and/or progesterone; and normal male and orchiectomized rats treated with vehicle or testosterone. Female rats in diestrus had a slower gastric emptying and a lesser geometric center value than ovariectomized rats. Estradiol inhibited gastric emptying but did not affect gastrointestinal transit. Progesterone increased gastric emptying. Progesterone at lower dose (10 mg/kg) decreased the geometric center compared with higher doses (20 or 40 mg/kg) or vehicle controls. A mixture of estradiol (10 micrograms/kg) and progesterone (20 mg/kg) inhibited gastric emptying to a similar degree as estradiol (10 micrograms/kg) did. Testosterone had no influence on gastric emptying or gastrointestinal transit. These results suggest that estradiol and a mixture of estradiol and progesterone inhibit, whereas progesterone enhances, gastric emptying. Testosterone did not play a role in gastrointestinal motility.

Animals↗
PubMed1990

[Gastrointestinal transit time (GITT) in normal Chinese and patients].

Two kinds of radiopaque pellets were ingested as markers to determine GITT in 60 normal subjects, 7 patients with ulcerative colitis (UC), 10 patients with idiopathic constipation (IC) and 8 patients with other diseases. The food contained 10-20g dietary fiber per day. Besides, GITT was determined in 14 normal subjects whose dietary content was 40-50g or 10g MO YU and 10-20g dietary fiber per day. Results are expressed in hours as 50% transit time (mean +/- s) and the values or normal subjects are as the follows: total GITT 25.0 +/- 7.3h, mouth iteum TT 9.0 +/- 3.3h, colonic TT 15.9 +/- 7.5h. There was no difference in age or sex groups. However, in high dietary fiber or MO YU group, GITT shortened significantly. Abnormal GITT was shown in patients with UC, IC, other gut and systemic diseases. In conclusion, the method employed in the present study is simple, safe and useful in the clinical study of gastrointestinal motility; and may provide important information to elucidate the pathophysiology of the diseases related to disorders in motility of the digestive tract.

Adult↗
PubMedDate not supplied

Pharmacologic modulation of motility.

Etiologically, gastroesophageal reflux disease (GERD) can be regarded as motility disorder: Although blocking acid is effective in the treatment of GERD, it does not overcome the underlying pathologic factors that allow acid, pepsin, and bile to reflux into the esophagus. Prokinetic agents address the upper gastrointestinal motility disturbances contributing to GERD and, thus, have an important role in the short- and long-term medical management of reflux esophagitis. This paper discusses the rationale for the effectiveness of pharmacologic modulation by reviewing current concepts and postulated theories about the mechanisms underlying the neuromuscular abnormalities. The multifactorial aspects of GERD are addressed and the potential for tailoring medical therapy also emphasized.

Bethanechol↗
PubMed1997

Nitric oxide modulates the acute increase of gastrointestinal transit induced by endotoxin in rats: a possible role for tachykinins.

Because of the evidence that endogenous nitric oxide (NO) plays an essential role in the physiological regulation of gastrointestinal motility we have investigated, by use of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), the role of endogenous NO in the acute endotoxin-induced changes of gastrointestinal transit. Pre-treatment with E. coli endotoxin (100 micrograms kg-1, i.v.) induced a significant increase in the gastrointestinal transit of a charcoal suspension in anaesthetized rats. Previous administration of the NO synthase inhibitor, L-NAME (10 mg kg-1, i.v.) significantly prevented the effects of endotoxin. L-arginine (200 mg kg-1, i.v.) and the substance P antagonist [D-Pro2, D-Trp7,9]-substance P (SPA), significantly reversed the effects of L-NAME on gastrointestinal transit in rats treated with endotoxin. Pre-treatment with dexamethasone (5 mg kg-1, s.c., twice), an inhibitor of the expression of inducible NO synthase, did not affect the increase in the gastrointestinal transit through constitutive NO synthesis. The results suggest that constitutive nitric oxide is involved in the increase of gastrointestinal transit induced by endotoxin and that the reduction in transit induced by L-NAME in endotoxin-treated rats is mediated by endogenous tachykinins.

Animals↗
PubMed1989

Are relaxation oscillators an appropriate model of gastrointestinal electrical activity?

Mathematical models based on relaxation oscillators have heavily influenced the terminology and experimental designs of investigations in gastrointestinal motility for nearly two decades. Relaxation oscillator equations have been used to stimulate the electrical activities of the esophagus, stomach, small intestine, colon, and rectosigmoid region. It has been suggested that many attributes of gastrointestinal electrical activity cannot be adequately explained by classic "core-conductor" or "cable" models of excitation and conduction. This article critically reviews the relaxation oscillator model and provides an explanation for each of the putative inadequacies of core-conductor theory. Furthermore, we question whether relaxation oscillator equations are able to simulate the waveforms of gastrointestinal slow waves, alterations in waveform in response to drugs or electrical stimulation, patterns of slow-wave activity when stimulated at physiological frequencies, prolonged periods of constant resting membrane potential between gastric slow waves and electrotonic spread into inactive regions. We conclude that the relaxation oscillator equations do not fully describe gastrointestinal electrical activity; excitation and propagation can be modeled by a theory that provides for morphological features, ionic conductances, and other elements included in the cable equations.

Animals↗
PubMed2003

Can the USP paddle method be used to represent in-vivo hydrodynamics?

Experiments in-vitro and in dogs were conducted to find in-vitro hydrodynamic conditions that can be used to represent gastrointestinal motility patterns. Specifically, the dissolution performance of micronised and coarse-grade felodipine (a poorly soluble, neutral, lipophilic drug) was studied in a biorelevant medium in the USP paddle apparatus at various paddle speeds. Ratios of percentage dissolved (slower:faster rev min(-1)) were calculated pairwise. These ratios were then compared with AUC ratios obtained in a corresponding pharmacokinetic study in Labradors, in which the absorption of both the micronised and coarse-grade felodipine had been compared under two gastrointestinal hydrodynamic conditions. Using a paddle speed combination of 75 and 125 rev min(-1) to represent the motility patterns in response to administration of normal saline and 5% glucose, respectively, the in-vitro ratios (75:125 rev min(-1) dissolution ratio was 91% for the micronised and 46% for the coarse-grade powder) showed good agreement with the pharmacokinetic data (saline-to-glucose absorption ratio was 98% for the micronised and 46% for the coarse-grade powder). It was concluded that, provided an appropriate composition is chosen for the dissolution test, the USP paddle apparatus can be used to reflect variations in hydrodynamic conditions in the upper gastrointestinal tract.

Animals↗