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An immunohistochemical study on the endocrine cells in the gastrointestinal tract of domestic duck.

Endocrine cells in the gastrointestinal tract of the domestic duck were identified immunocytochemically using antisera specific to bombesin, chromogranin A, cholecystokinin (CCK), gastrin, glucagon, neuron specific enolase (NSE), neurotensin, secretin, 5-hydroxytryptamine (5-HT), somatostatin, substance P and vasoactive intestinal polypeptide (VIP). Chromogranin A, 5-HT and somatostatin immunoreactive cells were widespread throughout the gastrointestinal tract. Bombesin immunoreactive cells were observed only in the proventriculus and the gizzard. CCK, substance P and neurotensin immunoreactive cells were present in the intestinal tracts from the duodenum to the colorectum. The latter were numerous also in the antrum. Gastrin cells were peculiar to the antrum but present also in the gizzard and small intestine. Glucagon immunoreactive cells were present in the jejunum-ileum and above all in the large intestine. Only few secretin cells were present in the duodenum. The highest frequency of endocrine cells was found in the antrum, while the lowest was observed in the caeca. Antisera to somatostatin and substance P showed numerous nerve cells and fibers besides endocrine cells, whereas NSE and VIP immunopositivity was found in the nervous structures only of the gut wall.

APUD Cells↗

Innate immune defence in the human gastrointestinal tract.

The mucosal surface of the gastrointestinal tract represents a major entry point and ecological niche for many microbes. It forms an important immune barrier, absorbing nutrients, whilst preventing invasion by organisms. Of the extra-ordinarily diverse species that comprise the microbial world, relatively few organisms are able to succeed in breaching this barrier in an otherwise healthy host. The production and secretion of antimicrobial peptides (AMPs) from surface epithelia and circulating immune cells are likely to play a key role in host protection and homeostasis. A number of these peptides are constitutively produced providing resident protection, whereas others are induced during infection and inflammation. In addition to directly eradicating microorganisms, it is becoming increasingly apparent that AMPs are multi-functional with diverse immuno-modulatory properties. This review focuses on three families of AMPs, defensins, cathelicidins, and lysozyme, and discusses their role in mucosal defence.

Antimicrobial Cationic Peptides↗

[Drug-induced anomalous contraction of gastrointestinal tract of mice with impaired c-kit function].

Drug-induced contraction of gastrointestinal tracts seems to depend upon the extent of their rhythmic contraction that is driven by the activity of gastrointestinal pacemaker cells. In BALB/c mice chronically administrated with a neutralizing anti-c-Kit monoclonal antibody (ACK2), rhythmic contraction of the gastrointestinal tract was impaired and contractile responses to drugs, including acetylcholine, prostaglandin F(2alpha), and bradykinin, were anomalously augmented. Histochemical analysis of the c-kit-positive cells in the gastrointestinal tract revealed the decreased number of c-kit-positive cells in the ACK2-treated animals, which lead to the impaired rhythmic contraction. Since the intestinal c-kit-positive cells in primary culture developed Ca(2+)-dependent rhythmic Cl(-) current, the rhythmic current is supposed to be an origin of gastrointestinal pacemakers. The extent of anomaly in drug-induced contraction correlated with the extent of impairment in rhythmic contraction. The drug-induced anomalous contraction in the preparation from ACK2-treated animals, which is accompanied by the impaired rhythmic contraction, was mimicked when the gastrointestinal segments from control animals were superfused with a low temperature organ bath solution at 25 degrees C. These results suggest that rhythmic discharge of excitation of smooth muscle cells, which is triggered by rhythmic excitatory input from c-kit cells, regulates the extent of drug-induced contraction.

Animals↗

Turnover of S35-sulfate in the mucosa of the gastrointestinal tract of rats as seen in autoradiograms.

Segments of the gastrointestinal tract removed from rats after intervals of time following injection of S(35)-sulfate were fixed in aqueous formalin and then washed in water. Contact and coated autoradiograms were prepared. The suggestion made by others that more of the labelled sulfate is fixed by the mucosa than by the underlying coats of the gastrointestinal tract is confirmed. In addition it was found that the isotope is fixed to a greater extent in the lower intestine than in the middle or upper portions of it. Coated autoradiograms revealed that 6 hours after administration of S(35)-sulfate more of the label was present in the goblet cells lying deep in the crypts of the mucosa than in those adjacent to the intestinal lumen. By the 24th hour the concentration of the isotope was strikingly higher and more uniform from cell to cell. The mucus in the intestinal lumen was also highly radioactive. At the end of 48 hours very little of the sulfur-35 remained in the intestinal wall or could be made out in the mucus of the lumen: the autoradiographic reaction was faint and diffuse as contrasted with the punctiform and intense reaction given by the specimens removed at the end of shorter intervals of time.

Animals↗

[Gastrointestinal tract leiomyomas].

The authors describe four cases of gastrointestinal tract leiomyomas. In two cases the leiomyomas were situated in the stomach, in one case in the duodenum, and in one case in the small intestine. In the stomach the diagnosis was made by endoscopy while in the duodenum and small intestine by angiography. The authors stress the value of angiography in the diagnosis of leiomyomas in the parts of the gastrointestinal tract inaccessible to endoscopic examination.

Adult↗

The role of cyclooxygenase selective inhibitors in the gastrointestinal tract.

This article reviews the gastrointestinal manifestations of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and the improved gastrointestinal safety profile of cyclooxygenase selective (COX)-2 inhibitors. By inhibiting the COX enzyme, NSAIDs provide effective analgesia and suppress inflammation in a variety of conditions. Most NSAIDs (nonselective or traditional) not only inhibit prostaglandins at sites of inflammation but also inhibit prostaglandins that have important normal functions in other parts of the body. This may be harmful when normal gastrointestinal mucosal function is impaired and mucosal damage occurs. Although such damage is often trivial and usually not symptomatic, gastrointestinal ulceration may produce pain and, more ominously, lead to bleeding, perforation, or obstruction. A new approach to the gastrointestinal complications of NSAIDs became feasible with the discovery of two isoforms of COX, COX-1 and COX-2, with COX-1 expressed mainly in the gastrointestinal tract. The development of NSAIDs that preferentially inhibit COX-2 offers the promise of relieving pain and inflammation without the side effects attendant to COX-1 blockade. In prospective studies evaluating gastrointestinal ulceration with COX-2-specific NSAIDs, rates of endoscopic ulceration have been equivalent to those with placebo and much lower than those with nonselective NSAIDs. In the recently released studies of gastrointestinal outcomes (perforated, painful, or bleeding ulcers), incidence of clinically relevant ulceration with COX-2 NSAIDs is much lower than that of traditional NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗

Upper gastrointestinal tract: villous tumors.

Villous tumors of the upper gastrointestinal tract are unusual. A review of the surgical experience at the Mayo Clinic disclosed 18 such tumors in 16 patients. Nine were in the stomach; two of these arose near the esophagogastric junction and appeared to be esophageal masses. Nine villous tumors arose in the duodenum and six of these originated near the papilla of Vater and produced obstructive jaundice. The total group of patients consisted of nine men and seven women aged 35-78 years. All tumors were malignant, with changes ranging from carcinoma in situ to invasive grade 3 adenocarcinoma. The malignancy rate in previous reports has been only 55%. The radiographic characteristics of villous tumors appearing as lesions within the esophagus and within the common bile duct have not been previously described in the literature. The basic features of villous tumors of the upper gastrointestinal tract are the same as those of their more common counterparts in the colon.

Adenoma↗

Regulatory peptide and serotonin content and brush-border enzyme activity in the rat gastrointestinal tract following neonatal treatment with capsaicin; lack of effect on epithelial markers.

The possible trophic influence of the capsaicin-sensitive extrinsic innervation of the gastrointestinal mucosa was investigated. Rats were treated neonatally with capsaicin. The gastrointestinal content of serotonin and glucagon-like immunoreactivity were used as a measure of the effect on the endocrine gut mucosa and gastrointestinal aminopeptidase and alkaline phosphatase activities were used as a measure of the effect on the gut brush-border. The gastrointestinal content of the neuropeptides substance P, VIP and CGRP were used to monitor effects on the innervation of the gut. The depletion of substance P-immunoreactivity(-IR) and calcitonin gene-related peptide(CGRP)-IR in extracts of urinary bladder and lung from the capsaicin-treated rats is evidence of the efficacy of capsaicin treatment in affecting a loss of C-fibre sensory nerves. The significant depletion of CGRP-IR measured in the stomach and duodenum of capsaicin-treated rats indicated the loss of the C-fibre sensory innervation to the gastrointestinal tract. The gastrointestinal content of VIP and substance P, which are predominantly within intrinsic gut neurones, were unaffected by capsaicin treatment. In all regions of the gastrointestinal tract of capsaicin-treated rats, the serotonin and glucagon-IR levels were not significantly different from those in controls. Similarly the levels of activity of the brush-border enzymes were not significantly effected by capsaicin treatment. This suggest the absence of any major trophic influence of capsaicin-sensitive sensory nerves on the gut endocrine mucosa and the brush border.

Alkaline Phosphatase↗

Endoscopic sonography of the upper gastrointestinal tract.

Endoscopic sonography was used to examine the upper gastrointestinal tract of 550 patients referred for evaluation of abnormal findings seen on conventional endoscopy, upper gastrointestinal series, and CT. This essay illustrates the potential uses and limitations of this technique. Special emphasis has been given to the use of landmarks to facilitate orientation of the transducer in both the esophagus and stomach. Specific examples demonstrate involvement of individual layers of the bowel wall in both benign and malignant processes. It is stressed that this is a combined procedure requiring both an endoscopist and a radiologist. Endoscopic sonography is a valuable new technology with substantial potential in the evaluation of the upper gastrointestinal tract.

Digestive System↗

Allergic disorders of the gastrointestinal tract.

Allergic disorders of the gastrointestinal tract were once thought of as primarily dermatological manifestations of common food allergens such as peanuts. Recently, greater attention to these products has arisen as complex mechanisms of action have been more clearly delineated. Specific disease states have recently been recognized associated with gastrointestinal reactions to foods, such as celiac disease, infantile formula protein intolerance, and eosinophilic gastroenteritis have been well described. More recently, eosinophilic esophagitis and allergic constipation have been described. This article will review current information regarding the commonly identified gastrointestinal allergic states, and more detailed information regarding two new allergic entities will also be described.

Allergens↗

New therapeutic approach to corrosive burns of the upper gastrointestinal tract.

The therapeutic approach to the management of corrosive burns of the upper gastrointestinal tract leaves a considerable morbidity and a heavy mortality rate. This work evaluates the effectiveness of a new therapeutic approach given to 94 consecutive patients. The management has been based on three major points: (1) the definition of extent of upper gastrointestinal lesions by immediate fibroendoscopy; (2) immediate protection of the upper gastrointestinal tract by total parenteral nutrition in cases with serious burns (41 cases), normal oral nutrition being allowed for minor burns (35 cases); (3) reparative surgical procedures for any of the sequelae of such burns during the fibrosing phase. The results were as follows: (a) healing, depending upon the degree of burn, occurred between eight to 90 days; (b) the frequency of subsequent local complications was small with total parenteral nutrition started a few hours after ingestion of the corrosive product; (c) after reconstructive surgery no serious complications occurred; (d) the overall morbidity stayed at a very low level (four patients). We conclude that the general prognosis of a severe burn of the upper gastrointestinal tract, without other trauma, is appreciably improved by the very early institution of total parenteral nutrition.

Adolescent↗

Vasculature of various locations of canine gastrointestinal tract responds differently to intravenous isoproterenol.

In this study we investigated the relative vascular response of different locations of the gastrointestinal tract to continuous intravenous infusion of isoproterenol (0.1 microgram kg-1 min-1 for 10 min). The vascular response of some nonsplanchnic organs was also examined. Blood flow of the arteries was measured by electromagnetic flowmetry and that of the tissues by 15-micron microspheres. Isoproterenol increased (P less than 0.05) blood flow of the axillary artery (+52%), and the superior mesenteric artery (+45%), but not that of the inferior mesenteric artery. In the nongastrointestinal tissues, isoproterenol increased (P less than 0.05) the blood flow of the left (+46%), and right ventricle (+85%), and the skeletal muscle (+100%). In the gastrointestinal tract, isoproterenol increased (P less than 0.05) blood flow in the esophagogastric junction (+505%) and antrum (+1511%) only, but not in the gastric body or in any location of the small or large intestine. The drug also caused a large fall in resistance in the esophagogastric junction (-74%) and antrum (-94%), and a small, but significant fall in the duodenum, jejunum, and in the mid-small intestine. It had no significant effect on vascular resistance in the gastric body, ileum, or colon. In those locations of the gastrointestinal tract where isoproterenol caused an increase in blood flow, this effect was confined to the combined mucosal plus submucosal layer, and the drug had no effect on the muscularis. These data suggest that different locations of the gastrointestinal tract respond differently to the same circulating concentration of isoproterenol. The mechanism of this difference in response merits further investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of muscarinic receptor subtypes and interstitial cells of Cajal in the gastrointestinal tract of healthy dairy cows.

OBJECTIVE: To describe the distribution of muscarinic receptor subtypes M(1) to M(5) and interstitial cells of Cajal (ICCs) in the gastrointestinal tract of healthy dairy cows. SAMPLE POPULATION: Full-thickness samples were collected from the fundus, corpus, and pyloric part of the abomasum and from the duodenum, ileum, cecum, proximal loop of the ascending colon, and both external loops of the spiral colon of 5 healthy dairy cows after slaughter. PROCEDURES: Samples were fixed in paraformaldehyde and embedded in paraffin. Muscarinic receptor subtypes and ICCs were identified by immunohistochemical analysis. RESULTS: Staining for M(1) receptors was found in the submucosal plexus and myenteric plexus. Antibodies against M(2) receptors stained nuclei of smooth muscle cells only. Evidence of M(3) receptors was found in the lamina propria, in intramuscular neuronal terminals, on intermuscular nerve fibers, and on myocytes of microvessels. There was no staining for M(4) receptors. Staining for M(5) receptors was evident in the myocytes of microvessels and in smooth muscle cells. The ICCs were detected in the myenteric plexus and within smooth muscle layers. Distribution among locations of the bovine gastrointestinal tract did not differ for muscarinic receptor subtypes or ICCs. CONCLUSIONS AND CLINICAL RELEVANCE: The broad distribution of M(1), M(3), M(5), and ICCs in the bovine gastrointestinal tract indicated that these components are likely to play an important role in the regulation of gastrointestinal tract motility in healthy dairy cows. Muscarinic receptors and ICCs may be implicated in the pathogenesis of motility disorders, such as abomasal displacement and cecal dilatation-dislocation.

Animals↗

Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice.

Bromelain is a mixture of proteinases derived from pineapple stem that is marketed by health food stores as a "digestive aid". A number of studies suggest that bromelain may also have anti-inflammatory activity in vivo, including an anecdotal report describing potential efficacy in inflammatory bowel disease. We and others have previously shown that proteolytically active bromelain removes certain cell surface molecules and affects leukocyte migration, activation, and production of cytokines and inflammatory mediators in vitro. The purpose of this study was to determine whether ingested bromelain retains proteolytic activity within the murine gastrointestinal tract in vivo. The proteolytic activity of bromelain was determined in vitro using model substrates or immunofluorescence assays after administration of various doses and formulations orally to mice. Immune responses against bromelain were detected by enzyme immunoassays. When formulated in antacid, oral bromelain retained substantial proteolytic activity throughout the gastrointestinal tract. Bromelain concentrations within the colon were dependent on both dose and formulation and were sufficient to remove bromelain-sensitive molecules from both leukocytes and colon epithelial cells. Peak activity in the stool was observed 4 h after oral dosing. Although anti-bromelain IgG was detected in both serum and stool after long-term oral therapy, these antibodies did not prevent bromelain proteolytic activity within the gastrointestinal tract. These studies demonstrate that bromelain enzymes can remain intact and proteolytically active within the murine gastrointestinal tract. They provide further support for the hypothesis that oral bromelain may potentially modify inflammation within the gastrointestinal tract via local proteolytic activity within the colonic microenvironment.

Administration, Oral↗

Sumatriptan absorption from different regions of the human gastrointestinal tract.

Sumatriptan exhibits low oral bioavailability partly due to presystemic metabolism, which may vary with regional differences in metabolic activity throughout the gastrointestinal tract. This study evaluated sumatriptan absorption in humans after administration orally and by oroenteric tube into the jejunum and cecum. Because the site of cecal administration varied, pharmacokinetic parameters for sumatriptan and its major metabolite were compared statistically only after oral and jejunal administration. One-half of the oral dose was recovered in the urine as parent (3%) and metabolite (46%). Sumatriptan was absorbed throughout the gastrointestinal tract; absorption was similar after oral and jejunal administration, and less after cecal administration. The metabolite AUC and the AUC ratio (metabolite/parent) were significantly lower after jejunal compared to oral administration; the AUC ratio was two-fold lower after cecal administration. Results suggest that presystemic metabolism of sumatriptan varies throughout the gastrointestinal tract and/or regional differences exist in the absorption of metabolite formed within the gastrointestinal tract.

Administration, Oral↗

Misoprostol: new frontiers; benefits beyond the gastrointestinal tract.

Recent findings suggest that the protective role that misoprostol exerts in the gastrointestinal tract against nonsteroidal anti-inflammatory drug (NSAID) damage may be extended to a variety of other tissues and other noxious stimuli including those mediated by molecules such as interleukin 1 (IL-1), tumor necrosis factor (TNF), and endotoxin. The protective effects of misoprostol outside the gastrointestinal tract may involve prevention of triggering activities that would otherwise initiate a sequence of tissue damaging events. If this capacity of misoprostol to maintain homeostasis in a variety of settings is recognized, a cohesive pattern of action emerges. Numerous studies have shown that misoprostol is likely to act as a regulator within various cascades of immunological regulatory events. The in vitro and in vivo experimental data described in this paper suggest that the events which trigger episodes of pain and inflammation may be controllable by the administration of misoprostol. Mitigation of adverse effects of certain NSAIDs on renal function and cartilage metabolism has also been observed. Demonstration of this latter phenomenon in the clinical setting will greatly benefit the patient if it is shown to modify the arthritis disease process. The therapeutic applications of misoprostol beyond the gastrointestinal tract appear to be among the most interesting of therapeutic advances offered by any class of compound in the next decade. Because of the inflammatory and pain processes associated with arthritis disease progression, particular emphasis and confirmation through further clinical study should be placed on the potential effect of misoprostol on chondroprotection and synergy with NSAIDs.

Adjuvants, Immunologic↗

Muscarinic M(2) acetylcholine receptor distribution in the guinea-pig gastrointestinal tract.

In the enteric nervous system, acetylcholine is the most common neurotransmitter to induce gastrointestinal smooth muscle contractions. Cholinergic signaling is mediated by muscarinic acetylcholine receptors on the surface of smooth muscle cells. Five different muscarinic receptor subtypes (M(1)-M(5)) have been identified and characterized, all of which belong to the superfamily of the G-protein-coupled receptor. The muscarinic M(2) acetylcholine receptor is the major muscarinic receptor subtype expressed by smooth muscle tissues in the gastrointestinal tract, where it is coexpressed with a smaller population of M(3) receptor. In this study, we examined the immunohistochemical distribution of the M(2) receptor using a specific antibody in the guinea-pig gastrointestinal tract. M(2) receptor-like immunoreactivity was mainly observed as associated with smooth muscle cells in the gastrointestinal tract. M(2) receptor-like immunoreactivity in smooth muscle cells was distributed throughout the cell membrane associated with caveolae. In the proximal colon, M(2) receptor-like immunoreactivity in the smooth muscle cells was weak. In the small intestine, interstitial cells of Cajal that possessed neurokinin 1 receptor-like immunoreactivity had intense M(2) receptor-like immunoreactivity. In the proximal colon, intramuscular and myenteric interstitial cells of Cajal exhibited M(2) receptor-like immunoreactivity. These findings indicate that, in the gastrointestinal musculature, M(2) receptors are distributed both in the smooth muscle cells and interstitial cells of Cajal, suggesting that the M(2) receptor elicits smooth muscle cell contraction and the interstitial cells of Cajal are the sites of innervation by enteric cholinergic neurons.

Animals↗

Metabolism of vasopressin, oxytocin, and their analogues in the human gastrointestinal tract.

The bioavailability from the gastrointestinal tract of peptides as large as nonapeptides is very low, which may be attributed to extensive lumenal and mucosal degradation. The aim of the present study was to investigate the stability of the neurohypophyseal hormones arginine-vasopressin (AVP), oxytocin (OT), and their synthetic analogues in human intestinal contents, small intestinal brush-border membranes, and gastric, rectal, and colonic plasma membranes. Peptides were incubated in gastrointestinal contents from healthy volunteers and in human intestinal mucosa homogenates. The extent of degradation was determined by reversed-phase high performance liquid chromatography (HPLC). AVP was rapidly degraded in the ileum fractions of the intestinal contents whereas 50% of the analogue 1-deamino-8-D-arginine vasopressin (dDAVP) remained intact after 35 min. The degradation was pH dependent, and a concentration-dependent inhibition was observed when aprotinin, a proteinase inhibitor, was preincubated with contents from the ileum. No degradation of AVP, dDAVP, or oxytocin analogues was observed in the mucosa homogenate from the stomach. The peptides were found to be rather slowly degraded by intestinal microvilli membranes and colonic and rectal plasma membranes. This degradation occurred essentially when reduced glutathione 10(-4) M was added to the incubations. In conclusion, the major enzymatic barrier to intestinal absorption of OT, VP, and their analogues is present in the intestinal juice and not in the mucosa, which, however, constitutes a major physical barrier to peptide transport.

Adult↗