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PubMed2003

Expression of intermediate conductance potassium channel immunoreactivity in neurons and epithelial cells of the rat gastrointestinal tract.

Recent functional evidence suggests that intermediate conductance calcium-activated potassium channels (IK channels) occur in neurons in the small intestine and in mucosal epithelial cells in the colon. This study was undertaken to investigate whether IK channel immunoreactivity occurs at these and at other sites in the gastrointestinal tract of the rat. IK channel immunoreactivity was found in nerve cell bodies throughout the gastrointestinal tract, from the esophagus to the rectum. It was revealed in the initial segments of the axons, but not in axon terminals. The majority of immunoreactive neurons had Dogiel type II morphology and in the myenteric plexus of the ileum all immunoreactive neurons were of this shape. Intrinsic primary afferent neurons in the rat small intestine are Dogiel type II neurons that are immunoreactive for calretinin, and it was found that almost all the IK channel immunoreactive neurons were also calretinin immunoreactive. IK channel immunoreactivity also occurred in calretinin-immunoreactive, Dogiel type II neurons in the caecum. Epithelial cells of the mucosal lining were immunoreactive in the esophagus, stomach, small and large intestines. In the intestines, the immunoreactivity occurred in transporting enterocytes, but not in mucous cells. Immunoreactivity was at both the apical and basolateral surfaces. A small proportion of mucosal endocrine cells was immunoreactive in the duodenum, ileum and caecum, but not in the stomach, proximal colon, distal colon or rectum. There was immunoreactivity of vascular endothelial cells. It is concluded that IK channels are located on cell bodies and proximal parts of axons of intrinsic primary afferent neurons, where, from functional studies, they would be predicted to lower neuronal excitability when opened in response to calcium entry. In the mucosa of the small and large intestine, IK channels are probably involved in control of potassium exchange, and in the esophageal and gastric mucosa they are possibly involved in control of cell volume in response to osmotic challenge.

Animals↗
PubMed2004

Absorption pattern of trospium chloride along the human gastrointestinal tract assessed using local enteral administration.

BACKGROUND AND OBJECTIVES: The antimuscarinic drug trospium chloride is hydrophilic and therefore does not enter the CNS when used for the treatment of overactive bladder disturbances. However, the same property is the main reason for low and variable oral bioavailability. The present study was performed to assess the influence of intestinal site on absorption of the drug as the basis for the development of modified release preparations. METHODS: In a change-over pilot study, 8 healthy male volunteers received single 20 mg doses oftrospium chloride orally as a tablet (reference), as Eudragit-coated tablets dissolving at pH 6.0 (local administration into the small intestine), and rectally via a mini enema (corresponding to local administration into the large intestine). Plasma concentrations of trospium chloride were determined up to 36 hours after administration using GC/MS. RESULTS: Extent and rate of trospium chloride absorption declined rapidly upon administration into more distal regions of the gastrointestinal tract. C(max) (median: 6.42 ng/ml) and AUC(0.tlast) (42.28 ng/ml x h) were highest and t(max) (3.5 h) was shortest after administration of the reference tablet. AUC(0-tlast) reached 78% (90% CI 43 - 139%) after small intestine administration and 2% (90% CI 1 - 9%) following rectal administration, respectively, relative to the values for the oral tablet. CONCLUSION: Trospium chloride is absorbed primarily in the upper gastrointestinal tract. Development of modified release preparations must balance prolonged apparent absorption rates of the drug against a decrease in bioavailability.

Administration, Oral↗
PubMed1996

Review article: beta 3-adrenoceptor agonists--future anti-inflammatory drugs for the gastrointestinal tract?

The beta 3-adrenoceptor is now a recognized sub-type of beta-adrenoceptor and is the principle adrenoceptor responsible for lipolysis in rat adipocytes. The receptor is also found in the gastrointestinal tract where beta 3-adrenoceptor agonists are both spasmolytic and potent inhibitors of experimental non-steroidal anti-inflammatory drug (NSAID)-induced gastric and small intestinal ulcers. There is evidence to suggest that the underlying mechanism of protection involves enhancement of mucosal blood flow, possibly as a result of relaxation of vascular and non-vascular smooth muscle. This review examines some possible therapeutic applications for beta 3-adrenoceptor agonists in ulcero-inflammatory disorders of the gastrointestinal tract where an altered blood flow state is a component of the underlying pathogenic process.

Adrenergic beta-Agonists↗
PubMed2004

[Intraoperative enteroscopy in the diagnosis of recurrent gastrointestinal tract hemorrhage--case report].

The authors of this article point out the diagnostic scopes and advantages of the intraoperative endoscopy as one of the many diagnostic means, which may be employed to determine the cause of recurrent attacks of bleeding to the gastrointestinal tract. As an example demonstrating the scope of use of this relatively simple device, they present a case of examining a female patient with the recurrent attacks of bleeding to the gastrointestinal tract. Should other common diagnostic methods be employed, the case of the bleeding was impossible to discover.

Aged↗
PubMed2002

Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts.

Cytochrome P450 (CYP) enzymes in extrahepatic tissues often play a dominant role in target tissue metabolic activation of xenobiotic compounds. They may also determine drug efficacy and influence the tissue burden of foreign chemicals or bioavailability of therapeutic agents. This review focuses on xenobiotic-metabolizing CYPs of the human respiratory and gastrointestinal tracts, including the lung, trachea, nasal respiratory and olfactory mucosa, esophagus, stomach, small intestine, and colon. Many CYPs are expressed in one or more of these organs, including CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP2S1, CYP3A4, CYP3A5, and CYP4B1. Of particular interest are the preferential expression of certain CYPs in the respiratory tract and the regional differences in CYP expression profile in different parts of the gastrointestinal tract. Current research activities on the characterization of CYP expression, function, and regulation in these tissues, as well as future research needs, are discussed.

Cytochrome P-450 Enzyme System↗
PubMed1985

Topical prostaglandin E2 in the treatment of acute upper gastrointestinal tract hemorrhage. A prospective, randomized, double-blind study.

We performed a prospective, randomized, double-blind study to assess the efficacy of topical prostaglandin E2 (PGE2) in altering the course of patients with severe upper gastrointestinal tract hemorrhage. Forty-four patients with life-threatening, endoscopically proven hemorrhage were randomly allocated to receive either PGE2 or placebo for seven days. Severity of mucosal injury, determined by endoscopy, was scored both before and after completion of treatment. There were no significant differences between groups in either transfusion requirements or successful outcomes. However, the PGE2 group had significantly improved endoscopic injury scores while the placebo group did not. Therefore, topical PGE2 does not control acute hemorrhage from established upper gastrointestinal tract lesions, but it does result in an accelerated healing of established lesions.

Acute Disease↗
PubMed1987

Enkephalin convertase in the gastrointestinal tract an associated organs characterized and localized with [3H]guanidinoethylmercaptosuccinic acid.

Enkephalin convertase (carboxypeptidase EH; EC 3.4.17.10), a carboxypeptidase B-like enzyme which processes hormone and neuropeptide precursors, has been characterized in the gastrointestinal tract, submandibular gland, and pancreas using a binding assay with [3H]guanidinoethylmercaptosuccinic acid. Binding to homogenates of the membrane and soluble fractions of stomach, small intestine, colon, and submandibular gland is saturable, with Kd values of about 2 nM. Partial purification of the membrane fractions reveals a Co+2-stimulated carboxypeptidase B activity which is not detectable in crude homogenates. In vitro autoradiography with [3H]guanidinoethylmercaptosuccinic acid localizes enkephalin convertase to the epithelial cells of the stomach, colon, and intestine, the islet cells of the pancreas, and the acinar cells of the submandibular gland. This localization contrasts to the distribution of enkephalins and other neuropeptides in the gastrointestinal tract and associated organs, suggesting that enkephalin convertase may serve functions other than neuropeptide and prohormone processing.

Animals↗
PubMed1996

The gastrointestinal tract: an underestimated organ as demonstrated in an experimental LVAD pig model.

BACKGROUND: Although hemodynamic stability and renal function are important and are monitored closely in patients with implanted left ventricular assist devices (LVAD), the gastrointestinal tract may be underestimated in the early postoperative period with regard to adequate perfusion. We investigated renal, intestinal, and whole body metabolic changes in response to variations in LVAD flow and inspired oxygen concentration (FiO2). METHODS: Left ventricular assist devices were implanted in 10 adult pigs (weight, 55 +/- 1.76 kg). Renal vein (RV), superior mesenteric vein (SMV), and pulmonary artery (PA) blood oxygen saturation and lactate concentration were measured and used as tissue perfusion markers. These measurements were made at baseline and after changes in LVAD flow or FiO2. RESULTS: Oxygen saturation in the PA, SMV, and RV decreased significantly after a reduction in LVAD flow (P < 0.05), with a greater reduction in the SMV than in the PA and RV (p < 0.05 at LVAD flow 3.5L/min; p < 0.01 at LVAD flow 2.0 and 1.0 L/min). The lactate concentration in the PA and SMV increased significantly (p < 0.01) with decreased flow, with a greater increase in the SMV than in the PA (p< 0.05), whereas it remained unchanged in the RV. Oxygen saturation in the PA, SMV, and RV decreased significantly after a reduction in FiO2 (p < 0.05). Lactate concentration in the PA, SMV, and RV increased significantly at FiO2 of 0.10 (p < 0.05). Lactate concentration in the PA and SMV was significantly higher than that in the RV at Fi)2 of 0.10 (p < 0.01). CONCLUSIONS: The results show that the gastrointestinal tract is at high risk during low perfusion or low FiO2, whereas the kidneys' metabolic function appears to be less disturbed. In clinical practice, this emphasizes the need to ensure adequate blood flow and respiratory function, especially after extubation, in patients with implanted LVAD. This might avoid intestinal ischemia and subsequent endotoxemia. Gastrointestinal tonometry may help in the assessment of intestinal perfusion.

Animals↗
PubMed1986

Organ specific antigens of the human gastrointestinal tract.

We previously reported the characterization of a normal adult colonic mucin antigen which contained an organ specific immunodeterminant [Tissue Antigen 11, 362 (1978)]. In the present study we have investigated mucins produced at other levels of the gastrointestinal tract in order to determine if regional specificities exist. Mucins were isolated from normal adult stomach, jejunum, ileum and colon and used to prepare antisera in rabbits. By radioimmunoassay at least four distinct specificities were observed. Gastric, ileal and colonic mucins were shown to contain immunodeterminants which were organ specific. Antiserum directed toward jejunal mucin determinants was reactive with the entire gastrointestinal tract. However, by heterologous inhibition analyses employing purified mucins as inhibiting antigens, the anti-jejunum antiserum was shown to be capable of discriminating a determinant present in much higher epitope density within small intestinal mucins as compared to mucins of the stomach and colon. Thus, it appeared that immunologic determinants present within mucin type glycoproteins of the gastrointestinal tissues exhibit anatomic specificity. In each case the structure of the immunodeterminant was, or was dependent upon the presence of a sialic acid derivative.

Antigens↗
PubMed1984

Bacterial translocation from the gastrointestinal tracts of rats receiving thermal injury.

Rats receiving nonlethal thermal burns over 20 or 40% of their total body surface area were tested at various intervals for the translocation of indigenous bacteria from their gastrointestinal tracts to their mesenteric lymph nodes, peritoneal cavities, and bloodstreams. No indigenous bacteria were cultured from these organs of control rats or from rats receiving 20% burns. However, 44% of the rats receiving 40% burns exhibited viable Escherichia coli, Proteus mirabilis, Staphylococcus sp. and Clostridium sp. in their mesenteric lymph nodes 2 days after thermal injury. Bacterial translocation after burn stress also was tested in antibiotic-decontaminated rats monoassociated with E. coli. E. coli attained population levels in these animals of 10(8) to 10(9) per g cecum. E. coli translocated to 100% of the mesenteric lymph nodes of both the control and 40% burned rats. However, E. coli translocated at a greater incidence to the spleens, livers, and peritoneal cavities of the burned rats compared with translocation to these organs in control rats. The numbers of E. coli translocating to the mesenteric lymph nodes, spleens, and livers also were greater in the 40% burned rats than in control rats. By 14 days after thermal injury, the rats were able to clear E. coli from their spleens and livers, and the infection remained localized in the mesenteric lymph nodes. These results support the concept that the indigenous gastrointestinal flora or exogenous organisms colonizing the gastrointestinal tract are potential sources of septicemia after thermal injury.

Animals↗
PubMed2001

[Histology of Crohn disease type lesions in the upper gastrointestinal tract].

Most patients with Crohn's disease undergo upper endoscopy with biopsy at least once, and for the pathologist it is of utmost importance to classify the lesions observed in biopsy specimens from the upper gastrointestinal tract. Duodenal and gastric specimens present two patterns of inflammation: a focal inflammation, with the inflammatory process restricted to a few glands, and a discontinuous inflammation, with the inflammation involving the entire or at least large parts of the specimens. In the latter, the mucosal architecture is compromised. The occurrence of epitheloid granulomas may support the diagnosis of Crohn's disease, but is not mandatory. Crohn's disease can be recognized in specimens taken from the esophagus only if granulomas or giant cells are found beneath the epithelial layer. This review discusses the most important differential diagnoses of inflammatory lesions in the upper gastrointestinal tract.

Crohn Disease↗
PubMed1996

Mechanisms of action of cholecystokinin in the canine gastrointestinal tract: role of vasoactive intestinal peptide and nitric oxide.

This study defined the cholecystokinin (CCK)/gastrin receptor subtypes at which CCK octapeptide (CCK8) and gastrin 17 (G17)act on motor functions of the intact canine gastrointestinal tract. In the antrum, studies of tachyphylaxis and effects of antagonists showed that i.a. G17 acted through CCKB receptors to activate contractions, whereas CCK8 acted through A and B receptor subtypes to produce contractions. In the duodenum, i.a. G17 caused dose-dependent inhibition of electrical field-stimulated contractions, apparently by release of nitric oxide [blocked by N-nitro-L-arginine (L-NNA) or NG-L-arginine methyl ester]. These inhibitory effects were abolished by YM022 (a CCKB antagonist) but not by L-364, 718 (a CCKA antagonist). However, i.a. CCK8 increased electrical field-stimulated contractions and L-364, 718 reversed this effect. In isolated perfused segments of distal intestine, CCK8 caused inhibition and excitation and released vasoactive intestinal peptide (VIP) into the venous effluent. CCK tetrapeptide and G17 had inconsistent effects. Excitation and VIP release were inhibited by L-364, 718. L-NNA potentiated excitatory responses and abolished inhibitory responses. Tetrodotoxin and atropine abolished and hexamethonium reduced excitatory responses to CCK8, but L-NNA restored contractions after atropine treatment. Hexamethonium or L-NNA (but not atropine) reduced VIP release; CCK8 still enhanced it. L-364, 718 abolished hexamethonium-resistant contractions and VIP release. Thus, CCK/gastrin peptides act on neural receptors in intact canine gastrointestinal tract. In antrum, activation of neural CCKA or CCKB receptors initiates contractions. In intestine, CCKA receptors at pre- and postjunctional sites in enteric nerves mediate acetylcholine and VIP release. CCKB receptors mediate release of an inhibitory mediator, apparently nitric oxide, from postjunctional sites.

Animals↗
PubMed1982

[Multiple adenomas of the upper gastrointestinal tract with peripapillary carcinoma in Gardner syndrome].

A Gardner syndrome can be diagnosed, if an adenomatosis of the colon is associated with tumors of the bone and soft tissues and anomalies of dentition. Adenomas of the upper gastrointestinal tract may occur as well as some time after colectomy. A case report is given of a 51-year-old man suffering from Gardner syndrome, who had developed on the basis of an adenomatosis of the duodenum a peripapillary adenocarcinoma, which was treated successfully. This case report shows, that in patients with Gardner syndrome also the upper gastrointestinal tract should be searched for malignant disease.

Adenocarcinoma, Papillary↗
PubMed1997

Detection of guanylate cyclases A and B stimulated by natriuretic peptides in gastrointestinal tract of rat.

The ultracytochemical localization of membrane-bound guanylate cyclases A and B has been studied after stimulation with atrial natriuretic peptide, C-type natriuretic peptide and brain natriuretic peptide in the gastrointestinal tract of rat. The two isoforms are stimulated differently by the three peptides. The results showed that the atrial and C-type natriuretic peptides stimulated guanylate cyclase activity, whereas the brain peptide seemed not to activate enough of the enzyme to detect. The guanylate cyclase activity had a wider distribution in stomach and small intestine than in large intestine; nevertheless, the reaction product of guanylate cyclase A activity had a wider localization in the stomach, whereas the reaction product of guanylate cyclase B activity had a wider distribution in the small intestine. In the small and large intestine, we detected mostly similar localizations of guanylate cyclase activity irrespective of the peptide used; in the stomach the reaction products of guanylate cyclase A and B were detected in different cell types or in different sites of the same cell. In all the gastrointestinal tract, guanylate cyclase activity was detected mainly in three types of cells: exocrine and endocrine cells; undifferentiated and mature epithelial cells; and smooth muscle cells. These localizations of guanylate cyclase activity suggest its role in regulating glandular secretion, cellular proliferation and muscular activity.

Animals↗
PubMedDate not supplied

Vasoactive intestinal peptide (VIP) receptors in the canine gastrointestinal tract.

Vasoactive intestinal peptide (VIP) is a putative neurotransmitter in both the brain and peripheral tissues. To define possible target tissues of VIP we have used quantitative receptor autoradiography to localize and quantify the distribution of 125I-VIP receptor binding sites in the canine gastrointestinal tract. While the distribution of VIP binding sites was different for each segment examined, specific VIP binding sites were localized to the mucosa, the muscularis mucosa, the smooth muscle of submucosal arterioles, lymph nodules, and the circular and longitudinal smooth muscle of the muscularis externa. These results identify putative target tissues of VIP action in the canine gastrointestinal tract. In correlation with physiological data, VIP sites appear to be involved in the regulation of a variety of gastrointestinal functions including epithelial ion transport, gastric secretion, hemodynamic regulation, immune response, esophageal, gastric and intestinal motility.

Animals↗
PubMed2004

Effect of whole bowel irrigation on the pharmacokinetics of an acetaminophen formulation and progression of radiopaque markers through the gastrointestinal tract.

STUDY OBJECTIVES: We describe the effects of whole bowel irrigation on a delayed-release acetaminophen preparation. We compare the mechanical effect of whole bowel irrigation on the progression of radiopaque markers through the gastrointestinal tract between an experimental and a control group. METHODS: We performed a 2-armed, prospective, randomized, crossover volunteer study. In the experimental phase, subjects were administered a delayed-release acetaminophen preparation (75 mg/kg) along with a capsule containing radiopaque markers. We initiated whole bowel irrigation at 30 minutes after ingestion and continued until the rectal effluent was clear. Serum acetaminophen concentrations were measured at baseline and from 0.5 to 8 hours. Abdominal radiographs were obtained at the completion of whole bowel irrigation. In the control phase, whole bowel irrigation was not performed. The primary outcome measure was the effect on the area under the acetaminophen concentration versus time curve (AUC) between the 2 groups. RESULTS: Ten subjects participated in the study. We found an 11.5% reduction in the AUC, with the majority of the effect occurring in the delayed-release portion of the curve after the 2-hour mark. This reduction, however, was not statistically significant. Radiographs obtained at the end of whole bowel irrigation revealed radiopaque markers sequestered in the right hemicolon in 8 of 10 subjects. No discernible pattern was noted in the control arm. CONCLUSION: The effect of whole bowel irrigation on reduction of AUC for delayed-release acetaminophen preparation was not statistically significant. Whole bowel irrigation did appear to have a mechanical effect on the progression of radiopaque markers through the gastrointestinal tract, but the clinical significance of this finding is not clear.

Acetaminophen↗