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Neurally-mediated and neurally-independent beneficial actions of melatonin in the gastrointestinal tract.

Melatonin (N-acetyl-5-methoxytryptamine), originally discovered in the pineal gland, is now known also to be present in the gastrointestinal tract from the stomach to the colon. It is localized and likely synthesized in the enterochromaffin cells of the mucosal lining. Its functions in the gut generally seem to be protective of the mucosa from erosion and ulcer formation and to possibly influence movement of the gastrointestinal contents through the digestive system. In this brief review, we summarize the work documenting the function of melatonin in influencing bicarbonate secretion in the stomach and its role in preventing and repairing ulcers in the stomach and duodenum. Melatonin's actions in the control of bicarbonate secretion involve the central and peripheral sympathetic nervous systems and the actions are receptor mediated. Conversely, melatonin's actions in reducing ulcer formation also seemingly involve the ability of the indole to directly scavenge toxic oxygen-based reactants, e.g., the hydroxyl radical, and possibly to promote antioxidative enzyme activities. These same processes may be involved in the mechanisms by which melatonin promotes ulcer healing. Additionally, however, melatonin's effects on the healing of ulcers includes actions of blood flow in the margins of the ulcer and also on the sensory nerves. All indications are that melatonin has a variety of beneficial effects in the gastrointestinal tract. It is likely, however, that additional actions of melatonin on the digestive system will be uncovered.

Animals↗

Gastrointestinal transit in mice treated with various extracts of date (Phoenix dactylifera L.).

Dates are commonly consumed, especially in the Middle East, but their effect on gastrointestinal transit (GIT) has not been quantified. The effect of water and ethanol extracts from date flesh and date pits on the GIT in mice was studied. Fasted unanaesthetized male mice received by gavage either the vehicle (0.02 m/kg), or the extracts at doses of 0.01, 0.02 or 0.04 ml/kg. Two separate groups received either clonidine (1 mg/kg) or yohimbine (2 mg/kg). Two hours later, all animals were given a test meal containing charcoal and gum arabic in water. Thirty min thereafter, they were killed and the distance the charcoal column had traveled along the small intestine was measured. Compared with the control, the animals that received the ethanol and water extracts of both date flesh and pits emptied, in a dose-dependent manner, more of their gastrointestinal content. The increase in the GIT ranged from 4 to 22%. However, water extract from dialyzed date flesh induced a dose-dependent decrease in GIT that ranged from 4 to 24%. Clonidine exerted a significant decrease (68%), and yohimbine a significant increase (30%) in the GIT. Depending on the method of extraction, the date extracts may exert an increase or a decrease in GIT.

Administration, Oral↗

Comparison of the odds of isolation, genotypes, and in vivo production of major toxins by Clostridium perfringens obtained from the gastrointestinal tract of dairy cows with hemorrhagic bowel syndrome or left-displaced abomasum.

OBJECTIVE: To compare the frequency of isolation, genotypes, and in vivo production of major lethal toxins of Clostridium perfringens in adult dairy cows affected with hemorrhagic bowel syndrome (HBS) versus left-displaced abomasum (LDA). DESIGN: Case-control study. ANIMALS: 10 adult dairy cattle with HBS (cases) and 10 adult dairy cattle with LDA matched with cases by herd of origin (controls). PROCEDURE: Samples of gastrointestinal contents were obtained from multiple sites during surgery or necropsy examination. Each sample underwent testing for anaerobic bacteria by use of 3 culture methods. The genotype of isolates of C. perfringens was determined via multiplex polymerase chain reaction assay. Major lethal toxins were detected by use of an ELISA. Data were analyzed with multivariable logistic regression and chi2 analysis. RESULTS: C. perfringens type A and type A with the beta2 gene (A + beta2) were the only genotypes isolated. Isolation of C. perfringens type A and type A + beta2 was 6.56 and 3.3 times as likely, respectively, to occur in samples from cattle with HBS than in cattle with LDA. Alpha toxin was detected in 7 of 36 samples from cases and in 0 of 32 samples from controls. Beta2 toxin was detected in 9 of 36 samples from cases and 0 of 36 samples from controls. CONCLUSIONS AND CLINICAL RELEVANCE: C. perfringens type A and type A + beta2 can be isolated from the gastrointestinal tract with significantly greater odds in cattle with HBS than in herdmates with LDA. Alpha and beta2 toxins were detected in samples from cows with HBS but not from cows with LDA.

Abomasum↗

Resistance of Santa Ines, Suffolk and Ile de France sheep to naturally acquired gastrointestinal nematode infections.

A study was conducted to assess the breed resistance against nematode infections in Santa Ines, Ile de France and Suffolk male lambs over a 9-month period in São Paulo state, Brazil. Lambs were born during the winter (year 2000) and were weaned at 2 months of age. The animals were then housed and treated with anthelmintics to eliminate natural infections by gastrointestinal nematodes. In late October 2000, lambs were placed in a paddock, where they stayed until August of the following year. Fecal and blood samples were taken from each animal every 2 weeks. On the same day, a pasture sample was collected to determine the number of infective larvae on the herbage. To prevent deaths, individual treatment with anthelmintics was provided to lambs with fecal egg counts (FEC) higher than 4000 eggs per gram (EPG) or with a packed cell volume (PCV) lower than 21%. In August 2001, all animals were slaughtered and the worms present in samples of the gastrointestinal contents were identified and counted. Most of the Suffolk and Ile de France sheep received three to six anthelmintic treatments over a period of 7 months, while most of the Santa Ines were not treated. Reductions in PCV and plasma protein values associated with high FEC and worm burdens were recorded, particularly, in Suffolk and Ile de France lambs. Haemonchus contortus and Oesophagostomum columbianum burdens and number of nodular lesions caused in the large intestine by O. columbianum larvae were significantly lower in Santa Ines sheep. All three breeds showed similar Trichostrongylus colubriformis worm burdens. The relative resistance of Santa Ines young male sheep was superior to that of Suffolk and Ile de France sheep.

Abomasum↗

Intestinal streaming patterns in cholerrhoeic enteropathy and diverticular disease.

Streaming of gastrointestinal contents depends on the demonstration of differential rates of recovery of equal doses of two synchronously fed markers. There was no significant difference in the rate of throughput of polyethylene glycol (a liquid phase marker) and chromium sesquioxide (a solid phase marker) in healthy volunteers (n = 7) and hospital inpatients (n = 5) with normal bowel habit, so that streaming does not usually occur. In cholerrhoeic enteropathy (n = 5), however, the rate of throughput of polyethylene glycol was increased. In colonic diverticular disease (n = 7) the rate of throughput of polyethylene glycol was significantly lower. In cholerrhoeic enteropathy the liquid phase marker was excreted 1.5 times faster than the solid phase, but in the diverticular disease group the liquid phase was excreted 0.75 times more slowly than the solid phase marker. This may reflect the effects of colonic hypersegmentation on the relative distribution of the liquid and solid phases.

Adult↗

Effects of gravity on gastric emptying, intestinal transit, and drug absorption.

The effects of microgravity on the physiologic response of the human body, the physical properties of gastrointestinal contents, and the influence these responses have on drug absorption are becoming more and more critical as the duration of humans in the hostile space environment dramatically increases. In this environment, some conventional oral dosage forms may be severely limited as an effective drug regimen. To understand the effects of microgravity, one must first understand the basic forces acting on a particle moving through a walled-tube such as the small intestine: gravity (FG), buoyancy (FB), and drag (FD). These forces can be combined and rearranged into a dimensionless ratio of gravitational forces to viscous forces. This is the most important dimensionless group influencing the motion of a particle relative to the fluid. Gastric emptying is highly influenced by several factors: volume, calories, exercise, size, density, temperature, viscosity, osmolality as well as those factors associated with physiologic responses: splanchnic blood flow, body position, and electrolyte balance. This array of factors can lead to variability in drug plasma levels. In the absence of gravity, the factors of size and density would appear to be most directly altered due to their dependence on the force of gravity. Intestinal transit rate in a gravity environment is highly dependent on the motility state of the GI tract either fasted or fed partly due to the higher viscosities of chyme in the fed state. In space, the absence of gravity may tend to increase the transit rate along the small intestine by decreasing the dimensionless ratio of gravitational forces to viscous forces. In zero gravity, therefore, these alterations in GI emptying and intestinal transit rate could lead to erratic plasma levels and inefficient absorption.

Gastric Emptying↗

Restriction of oral intake of water for aspiration lung disease in children.

BACKGROUND: Primary aspiration of food and fluid is commonly seen in children with feeding and swallowing difficulties associated with a range of diseases and complex medical conditions. Respiratory sequelae and pneumonia are known to be associated with primary aspiration of ingested material, however causality between primary aspiration of specific food and fluid types and pulmonary effects in children is yet to be established in controlled trials. The relative pulmonary morbidity of aspiration of ingested food and fluid materials versus other causes of respiratory disease such as viral and bacterial causes, secondary aspiration of gastrointestinal contents and predisposing lung conditions such as chronic neonatal lung disease in a developing immune system is also unclear. Current management decisions for children who aspirate have to optimise oral nutrition and hydration, while reducing the risk of aspiration to preserve pulmonary integrity. This generally includes restricting aspirated food or fluids and providing texture-modified diets and thickened fluids. Young children frequently refuse thickened fluids providing a management dilemma for both families and health professionals. OBJECTIVES: Our objective was to evaluate the efficacy of restriction of oral water ingestion on the pulmonary status of children with thin fluid aspiration demonstrated on a modified barium swallow study. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Airways Collaborative Review Group Specialised Register, MEDLINE, EMBASE and CINAHL databases were searched by the Cochrane Airways Group. The latest search was performed in January 2005. SELECTION CRITERIA: All randomised controlled trials comparing restriction of oral intake of water with unlimited oral water ingestion were eligible to be included. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against a pre-determined criteria for inclusion. No eligible trials were identified for a paediatric population and thus no data were available for analysis. One trial in an adult population was identified and reported. MAIN RESULTS: No randomised controlled trials examining the efficacy of restriction of oral intake of water in the management of children with thin fluid aspiration were found. In a single study in an adult population with stroke, no significant differences were seen between a control group of oral water restriction and the experimental group of unlimited oral water ingestion on outcomes such as pneumonia, total oral fluid intake and dehydration. AUTHORS' CONCLUSIONS: There are no trials that have adequately evaluated the pulmonary effects of allowing or restricting oral water ingestion in children known to have primary aspiration of thin fluids. Thus, there is currently an absence of evidence to support a strict approach of full restriction of oral intake of water or support a more liberal approach of allowing oral water ingestion in children with primary aspiration of thin fluids.

Child↗

Toxico-kinetics, recovery efficiency and microsomal changes following administration of deltamethrin to black Bengal goats.

A study of the toxico-kinetics, recovery percentage from different substrates, cytotoxicity and role of cytochrome P450 and b5 of liver microsome in the metabolism of deltamethrin were carried out in female black Bengal goat. The ALD50 value of deltamethrin in goat by intravenous route lies between 0.2 and 0.6 mg kg-1. Intravenous disposition kinetics using a dose of 0.2 mg kg-1 showed that the maximum blood concentration of deltamethrin was recorded at 0.5 min, followed by rapid decline, and a minimum concentration was detected at 6 min after administration. The following values were obtained: Vdarea 0.148 (+/- 0.02) litre kg-1; t1/2 (alpha) 0.22 (+/- 0.02) min; t1/2 (beta) 2.17 (+/- 0.37) min; Kel 1.05 (+/- 0.24) min-1; AUC 4.30 (+/- 0.45) micrograms min ml-1; ClB 0.05 (+/- 0.006) litre kg-1 min-1; T-B 1.93 (+/- 0.58); fc 0.40 (+/- 0.05). After 10 min, liver retained the maximum residue, and heart, adrenal gland, kidney, spleen, fat and brain also held the insecticide; liver, fat, heart and spleen retained residue after 30 min, and bone, liver and fat retained residue after 60 min of intravenous administration. Oral absorption of deltamethrin was poor and inconsistent, and approximately 65% of administered dose was recovered from faeces and gastrointestinal contents. The excretion of deltamethrin through urine was meagre, and only 0.01 and 0.013% of the administered dose was recovered after 3 and 5 days of oral administration respectively. All the tissues retained the residue after 3 days; while fat, rumen, reticulum, omasum, abomasum, large and small intestine and bone retained the residue after 5 days of oral administration; and the percentage recoveries were 1.73 and 0.027 respectively. Deltamethrin reduced the level of cytochrome P450 content of liver microsomal pellet of goat after 5 days of oral administration. Histopathological examination of liver, kidney, heart, spleen brain and lung sections of treated goats did not reveal any pathological changes.

Absorption↗

Cytokine suppressive agent improves survival rate in rats with acute pancreatitis of closed duodenal loop.

This study was designed to evaluate the possible role of cytokines (IL-1 and TNF-alpha) in the pathogenesis of acute pancreatitis in the early stage of the disease and to evaluate the protective effect of the cytokine suppressive agent, FR167653, against pancreatic injuries. Acute pancreatitis was induced in rats by closed duodenal loop. However, the free passage for the gastrointestinal contents was maintained by inserting the tube into the duodenum. In this model, the survival rate was significantly decreased as compared with the control sham-operated rats at 48 h after induction of pancreatitis. Marked hyperamylasemia and a significant increase in pancreatic water and trypsin contents were observed at 24 h after induction of pancreatitis. Pancreatic subcellular redistribution of lysosomal enzyme cathepsin B from the lysosomal fraction to the zymogen fraction was also observed. However, treatment with FR167653 at a dose of 1.5 mg/kg (four times, every 6 h after induction of pancreatitis) significantly prevented all these pancreatic injuries, improving the survival rate. These results indicate that cytokines such as IL-1 and TNF-alpha may be involved in the pathogenesis of acute pancreatitis in the early stage of the disease, and that a cytokine-suppressive agent might be of therapeutic value for the treatment of acute pancreatitis.

Acute Disease↗

Autoradiographic observations on the distribution and metabolism of N'-/14C/nitrosonornicotine in mice.

The fate of the weak base N'-nitrosonornicotine (2'-14C-labeled) has been studied in mice. Whole-body autoradiography showed that the radioactivity was rapidly distributed throughout the body, which probably reflects an ability of the non-protonated compound to freely pass biological membranes and distribute evenly in the intra- and extracellular tissue water. Metabolites which were firmly bound to tissue macromolecules - retained throughout the observational period (24 h) - were present in the tracheobronchial and nasal mucosa, the liver, the submaxillary and sublingual salivary glands and the esophagus. Radioactivity in the lacrimal gland, the gastrointestinal contents, the urinary bladder, and gallbladder seems to be related to excretion of the substance and/or its metabolites. A binding to the melanin in the eye and hair was observed in vivo and in vitro. Experiments with mice pretreated with diethyldithiocarbamate and nialamide showed that these substances partially inhibited the metabolism of N'-/14C/nitrosonornicotine. CO2 was not recovered in the breath during the 4 h following the administration of N'-/14C/nitrosonornicotine.

Animals↗

Effects of intragastric and intravenous glucose on restraint model of stress ulceration.

Intragastric glucose prevents acute stress-induced gastric mucosal injury in the restrained rat. Because increased gastric contractions contribute to mucosal injury in this model and because parenteral glucose infusions have been shown to suppress gastric contractility, we hypothesized that centrally mediated responses to hyperglycemia might contribute to the cytoprotective effect of intragastric glucose. We compared intragastric and intravenous 25% glucose with saline infusions during cold restraint and measured their impact on gastric lesions, serum glucose levels, gastric residual volume (an indirect indicator of net gastric contractility), acidity, and mucin concentration. We found that both intravenous and intragastric glucose infusions increased serum glucose to over 500 mg/dl after 4 hr of stress. Intragastric glucose increased residual volume and gastric pH, as well as decreased gastric mucosal injury, but intravenous glucose had no effects on gastric function. We found that none of the potentially protective effects of intragastric glucose are mediated by central responses to hyperglycemia, and likewise that intravenous glucose has no effect on gastric mucosal injury.

Animals↗

Increasing antidumping effect of intestinal pacing with motor-active agents.

The aim was to determine whether cholecystokinin-octapeptide (CCK-OP), bethanechol Cl, or metoclopramide HCl would increase the antidumping effect of intestinal pacing in five dogs with truncal vagotomy and Roux gastrectomy. While recording electrical activity from the conscious animals, the amount of a 100-ml, 25% dextrose gastric instillate emptied in 20 min was determined during control tests, during tests with CCK-OP (500 ng/kg/hr), bethanechol (80 micrograms/kg/hr), or metoclopramide alone (600 micrograms/kg/hr) given intravenously or during tests using combinations of pacing and drugs. In other tests, intraluminal gastrointestinal pressure was measured during control and drug infusions. CCK-OP, which relaxed the proximal stomach, slowed emptying of the dextrose instillates (mean +/- SEM emptied, no pacing, no drug = 74 +/- 5 ml; CCK-OP alone = 34 +/- 5 ml; P less than 0.05). CCK-OP also enhanced the slowing effect produced by pacing (pacing alone = 41 +/- 7 ml; pacing plus CCK-OP = 19 +/- 8 ml; P less than 0.05). In contrast, bethanechol and metoclopramide, which did not alter proximal gastric motility, did not alter emptying or augment or diminish the effect of pacing. The conclusion was that the combination of pacing and CCK-OP slowed gastric emptying of the dextrose more than pacing alone and thus had a greater antidumping effect. In contrast, neither bethanechol nor metoclopramide enhanced the pacing effect.

Action Potentials↗

The effects of gamma-radiation on intestinal motor activity and faecal pellet expulsion in the guinea pig.

The effects of whole-body gamma-radiation (10 Gy) on intestinal motor activity was examined in the small and large intestine of the guinea pig 18 hr post irradiation. Neurally mediated relaxations of isolated gut bath preparations were generally unaffected. However, the contractile responses to direct smooth muscle stimulation with the cholinergic muscarinic agonist carbachol or ganglionic stimulation of intrinsic cholinergic motor neurones were significantly increased in the duodenum and colon but not the jejunum. This increased sensitivity to cholinergic stimulation was reflected in an increased contractility and a shift in the concentration-response curves for carbachol. The specificity of radiation actions for cholinergic mediated contractions was further supported by the observation that histamine-evoked contractions were unaffected. In a second series of experiments we examined the effects of gamma-radiation on the rate of pellet expulsion from freshly excised colons. Both colons from irradiated animals and nonirradiated colons exposed to carbachol showed significantly faster rates of pellet expulsion, indicative of increased propulsive motility. Pretreatment of animals with 0.5 mg/kg sc of the 5HT3 receptor antagonist Granisetron prevented the effect of radiation and reduced the pellet expulsion rate to below normal. These results indicate that gastrointestinal motility disturbances seen in organ-bath preparations of the intestine from rats exposed to whole-body gamma-radiation may be related to an increased sensitivity of the cholinergic muscarinic system.

Animals↗

Peristaltic transport of a non-Newtonian fluid: applications to the vas deferens and small intestine.

The problem of peristaltic transport of a non-Newtonian (Power law) fluid in a uniform and non-uniform tube has been investigated under zero Reynolds number and long wavelength approximation. A comparison of the results with those of Newtonian fluid model shows that the magnitude of pressure rise, under a given set of conditions, is smaller in the case of non-Newtonian fluid, when the flow behavior index n less than 1, at zero flow rate. Further, the pressure rise decreases as n decreases from 1, at zero flow rate, is independent of n at a certain value of flow rate, and increases if flow rate exceeds further. Also, at a given flow rate, an increase in the wavelength leads to a decrease in pressure rise and increase in the influence of non-Newtonian behavior. Pressure rise, in the case of non-uniform geometry, is found much smaller than the corresponding value in the case of uniform geometry. Finally, the analysis has been applied and compared with observed flow rates in the vas deferens in rhesus monkeys and in the small intestine.

Animals↗

Spontaneous esophageal rupture treated by conservative therapy.

The prognosis of spontaneous esophageal rupture of the esophagus worsens over time from disease onset to treatment and, in severe cases, may require surgery to save the patient's life. Patients appearing at the hospital considerably after esophageal perforation have no appropriate surgical alternatives and face poor prospects. We conservatively treated a severe case following 2-day lapse of after disease onset, managing a favorable outcome. A 58-year-old man who developed upper abdominal and back pain after vomiting from drinking was transferred to our institute in an emergency due to pain intensifying 2 days after the symptom onset. Chest X-ray revealed a large quantity of bilateral pleural effusion similar to gastrointestinal content, which we withdrew through intrathoracic drainage. Esophagography showed perforation of the esophagus. The patient's poor general condition, including septic shock and adult respiratory distress syndrome, contraindicated radical surgery, so we instituted conservative therapy such as continuous thoracic drainage hyperalimentation. Oral intake was started in month 4 after admission. The patient was discharged in good general condition 7 months after onset.

Drainage↗

Digestive constraints on an aquatic carnivore: effects of feeding frequency and prey composition on harbor seals.

We hypothesized that increased feeding frequency in captive harbor seals would increase nutrient loads and thus reduce retention time and the digestive efficiency of natural prey. We measured daily feed intake and excretion during 6 feeding trials and fed herring (49% lipid), pollock (22% lipid) or an equal mix of each diet over 24 months. Animals were accustomed to feeding at either high or low frequency. Body mass and intake did not vary with season. Although mean retention times were similar between diets and feeding frequencies, solute and particulate digesta markers separated at high feeding frequency. Consistent dry matter digestibility resulted in greater gut fill from pollock than from herring. Digestible energy intakes from pollock were approximately 25% greater than from either herring or the mixed diet. Lipid digestibility of herring declined from 90% to 50% when lipid intake exceeded 60 g kg(-0.75) day(-1). Our hypothesis of a trade-off between intake and digestion was not supported for protein but was supported for lipid. Results of this study imply that a flexible digestive system for harbor seals can compensate for ingesting prey of lower energy density by increasing gut fill and enhancing protein and lipid assimilation, to sustain digestible energy intake.

Animal Feed↗

Viscoelastic behaviour aids extrusion from and reabsorption of the liquid phase into the digesta plug: creep rheometry of hindgut digesta in the common brushtail possum Trichosurus vulpecula.

Temporal variation in the rheometric properties of the proximal and distal colonic digesta of an arboreal marsupial folivore, the common brushtail possum, was examined to assess flow behaviour during peristalsis, segmentation and other aspects of intestinal motility. The time-dependent rheometric characteristics on application of a constant shear stress within the physiological range showed an initial elastic and subsequent viscoelastic phase, which fitted Burger's model of creep compliance. Similarly, the time-dependent rheometric characteristics on recovery from shear stress fitted with a generalised two-component Maxwell model of elastic and viscoelastic components for creep recovery. Differences in the relative magnitudes of the viscoelastic components during recovery from those during shear indicated that the physical properties of the digesta plug changed with sustained shear stress, a phenomenon, which is likely to result from extrusion of the liquid phase from the solid elements of the digesta plug. There was significant viscoelastic recovery during the initial 4 s following cessation of stress, which would allow for prompt concomitant reabsorption of the liquid phase into the digesta plug. This supports a hypothesis of alternate extrusion and reabsorption of the liquid phase of the digesta plug. This would promote both nutrient absorption across the intestinal wall (from liquid extrusion) and enzyme permeation and digestion (from liquid absorption into the plug). However, the presence of a slower component of viscoelastic recovery indicates that liquid phase reabsorption into the digesta plug is incomplete if the interval before a subsequent contraction is less than 150 s, in which case unreabsorbed liquid may be driven either orally or aborally. This would at least partly account for differences in retention times of liquid and solid phase digesta markers reported for the gastrointestinal tracts of numerous vertebrate species.

Animals↗