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Review article: adrenergic control of motor and secretory function in the gastrointestinal tract.

The role that the sympathetic nervous system plays in modulating physiological processes in the gastrointestinal tract is becoming clearer. It is now known that motor, secretomotor and vasomotor activity are all modulated independently by the system. Adrenoreceptor stimulation appears to reduce intestinal contraction (except at sphincters), both via alpha-receptors which inhibit neurotransmitter release and also by a direct beta-receptor mediated action on smooth muscle. There is also evidence for tonic activity in the beta-adrenergic pathway, since beta-antagonists tend to increase contraction pressures. In animals alpha-receptor-mediated pathways modulate fluid and electrolyte absorption, and alpha-adrenergic agonists enhance net absorption and reduce net secretion. In man there is also evidence for a beta-adrenergic pathway which controls secretomotor function. Carbohydrate absorption appears to be dependent on activity in a beta-adrenergic pathway, although this may be an indirect effect of changes in motor function. The time course of changes of both secretomotor and motor activity, induced by modulating sympathetic or adrenergic input, differ from the vascular changes indicating that the effects occur independently of each other. The gastrointestinal response to stressors is mediated, in part at least, by the sympathetic nervous system. Differences between individuals are likely to prove important. Since the sympathetic nervous system regulates gastrointestinal function both in the basal state and under stressful conditions, it will have effects on pathophysiological responses. Modification of such responses is likely to ameliorate symptoms, as has already been found for alpha-2-adrenergic agonists which have an antidiarrhoeal action.

Animals↗

[Neuro-endocrine tumors of the gastrointestinal tract: epidemiology, classification, prognosis, diagnosis and therapeutic modalities].

The neuro-endocrine tumors of the gastrointestinal tract comprise a heterogeneous group of slow-growing malignancies with great differences regarding their localization, tissue of origin and their entopic and ectopic production of hormones. They can be subdivided in carcinoid tumors and endocrine tumors of the pancreas. According to their secreted products they manifest as endocrinological syndromes or as local space-occupying tumors. This review focuses, besides summarizing the available epidemiological data and describing tumor localization and classification, on the differing symptom complexes and the prognosis of the various tumor entities. Furthermore, the value of available diagnostic techniques and the role of different therapeutic modalities like surgery, radiation, biotherapy and cytostatic chemotherapy are discussed.

Carcinoid Tumor↗

Surgery for carcinoid tumours of the lower gastrointestinal tract.

INTRODUCTION: Carcinoid tumours are rare neoplasms that originate from neuroendocrine cells of the primitive gastrointestinal tract. Mid- and hind-gut tumours comprise the majority of these rare tumours. With many recent advances in medical treatment the role and importance of surgery and the surgeon needs to be assessed. METHOD: A Medline, Pubmed and Embase databases search was undertaken. All relevant articles were cross-referenced. RESULTS AND CONCLUSIONS: Incidental findings of carcinoid tumours should be treated at initial surgery whilst elective surgery and further management should be undertaken in specialist centres by a multidisciplinary team. Asymptomatic patients have a better prognosis than those with symptoms. In advanced cases surgery combined with chemotherapy and liver resection is appropriate. The outlook for the majority of cases is good.

Carcinoid Tumor↗

Rhythmic oscillating complexes in gastrointestinal tract of chickens: a role for motilin.

Rhythmic oscillating complex (ROC) is a highly organized gastrointestinal motility pattern recently described in fasted avian species. ROCs show several high-speed aborad-propagated contractions that progressively change into others of orad direction. In addition, chickens show migrating motor complexes (MMC) in both fed and fasting states. Recently, motilin was isolated and characterized from chicken small intestine. Accordingly, the aim of this study was to learn whether chicken motilin might be involved in either ROC or MMC induction. Electromyographic recordings were obtained from different areas of the gastrointestinal tract of chickens while motilin was infused. The response to chicken motilin was dose dependent in both fed and fasted animals; a bolus of 4 x 10(-11) mol/kg (n = 5) did not modify the intestinal motor pattern, whereas 4 x 10(-10) and 4 x 10(-9) mol/kg (n = 5 each) induced a complete ROC pattern of 5.2 +/- 0.6 and 10.8 +/- 0.9 min, respectively. ROCs induced by chicken motilin presented exactly the same pattern as that described during a spontaneous ROC. Furthermore, motilin concentration in plasma, measured by radioimmunoassay, increased during a spontaneous ROC. This study suggests that chicken motilin triggers an ROC in chickens. The fact that plasma motilin levels increased during spontaneous ROC strongly suggests that motilin is involved in the induction of the ROC pattern. Motilin seems to play a different role in avian and mammalian species, because a phase III of the MMC was never induced by motilin infusion.

Animals↗

Postnatal changes in bacterial populations in the gastrointestinal tract of dogs.

OBJECTIVE: To describe postnatal changes in the populations of bacteria in the gastrointestinal tract (GIT) of dogs. ANIMALS: 110 Beagles ranging from neonatal to adult dogs. PROCEDURE: Contents of the stomach and proximal and distal portions of the colon and contents and mucosa of the mid region of the small intestine were collected from puppies at 1 day after birth and subsequent suckling; puppies at 21, 42, and 63 days after birth; and adult female dogs (ie, dams of the puppies) for enumeration of bacterial populations. RESULTS: The entire GIT was colonized at day 1 by all groups of bacteria studied; aerotolerant forms were dominant. During subsequent postnatal development, there were changes in the relative proportions of the various groups of bacteria with anaerobic groups increasing in absolute and relative numbers. CONCLUSIONS AND CLINICAL RELEVANCE: Establishment of bacterial populations in the GIT of dogs is a gradual process that begins immediately after birth. Age-related changes in the relative proportions of bacterial groups coincided with changes in diet and physiologic processes of the host and can influence nutritional state and disease resistance of developing dogs. Differences among regions of the GIT suggest that fecal samples may have limited use for understanding the populations of bacteria and the age and diet-related changes in various regions of the GIT.

Aging↗

Proinflammatory effects of local abdominal irradiation on rat gastrointestinal tract.

Although the role of inflammatory processes in the genesis of late changes in the gastrointestinal tract following exposure to ionizing irradiation has been extensively studied, few studies have concentrated on the presence of an acute inflammatory response in the period immediately following radiation. We therefore examined, in rats, whether the local application of 10 Gy cobalt-60 irradiation to the abdomen led to changes in the gut within the first 24 hr that were consistent with an acute inflammatory response. In stomach, small intestine, and colon, local irradiation led to a significant increase in the accumulation of plasma within the tissue by 4-8 hr following irradiation. This increase in tissue plasma volume, indicative of an increased microvascular permeability, was then sustained until the end of the 24-hr assessment period in all tissues examined. Concurrent with this was a consistent transient increase in tissue red blood cell volume, suggestive of vasodilation. Of particular note, a significant increase in the number of mucosal neutrophils was also observed between 2 and 12 hr following irradiation. This elevation in mucosal neutrophils was particularly marked in the pericryptal or deep mucosal regions of small intestine and colon and consistently preceded the vasodilation and enhanced permeability. Furthermore these pathophysiological alterations occurred at a time when histological changes in the mucosa consistent with an impaired mucosal microcirculation (ie, edema of the lamina propria and subepithelial bleb formation) were present. These results support the hypothesis that an inflammatory response occurs in the gut during the first 24 hr following abdominal irradiation. Such changes may then further exacerbate the damage initiated by the ionizing radiation.

Acute Disease↗

Distribution of a novel pituitary protein (7B2) in mammalian gastrointestinal tract and pancreas.

The distribution of a novel pituitary protein (7B2) was determined in the gastrointestinal tract and pancreas of four mammalian species (man, pig, guinea pig, and rat) by a specific radioimmunoassay. The highest concentrations of cross-reacting immunoreactive 7B2 (IR-7B2) were observed in the pancreas and the proximal gut (antrum or duodenum). While the intestinal concentrations varied widely among species, pancreatic IR-7B2 concentrations appeared to be similar in all four species. In the rat, pancreatic islets were found to contain high concentrations of IR-7B2 (5.73 +/- 0.14 fmol/islet, mean +/- SEM). Neonatal capsaicin treatment and enteric nerve section did not affect the concentrations of IR-7B2 in the rat intestine. Layer separation of human gut showed that IR-7B2 is mainly (71 +/- 8%) present in the epithelial fraction. Chromatographic analysis of intestinal and pancreatic extracts from the four species on Sephadex G-100 showed the presence of two immunoreactive peaks at Kav 0.3 and 0.6, but there were both inter- and intraspecies variations in the proportions of the larger and smaller molecular forms.

Animals↗

Cytochemical and ultrastructural differentiation of enteroglucagon and pancreatic-type glucagon cells of the gastrointestinal tract.

Coordinated studies have been carried out on the glucagon immunoreactive cells of the mammalian gastrointestinal tract (man, dog, rat), using electron microscopy, silver staining and immunocytochemistry. Parallel ultrastructural and immunocytochemical studies have been made with the semithin-thin serial section technique. The results indicate that while the glucagon cells of the oxyntic portion of the stomach are virtually indistinguishable from those of the pancreatic islets (A cells) those of the intestine (EG cells) are completely different. Proper identification of glucagon immunoreactive cells requires the application of morphological and silver staining techniques, at the ultrastructural level.

Animals↗

Autoradiographic localization of sigma opioid receptors in the gastrointestinal tract of the guinea pig.

The distribution of sigma and phencyclindine binding sites in the gastrointestinal tract of the guinea pig was studied by autoradiography after in vitro incubation of tissue slices with (+)3H-SKF 10,047 and 3H-1-1-[(2-thienyl)cyclohexyl] piperidine to locate sigma and phencyclidine receptors, respectively. A dense distribution of sigma binding sites was observed in the mucosa and in the submucosal plexus, particularly at the level of the fundus and duodenum. Muscular layers were only marginally labeled. No phencyclidine binding site could be demonstrated in any area. This selective distribution suggests a functional role of sigma receptors mainly in the control of endocrine or exocrine secretions, or both.

Animals↗

The effect of intraperitoneally administered microcystin-LR on the gastrointestinal tract of Balb/c mice.

Microcystin-LR (MCLR) has been associated with the development of gastrointestinal complaints in people ingesting cyanobacterial bloom contaminated water. The symptoms usually present a day or two after exposure raising questions as to the toxic effects of MCLR on the gastrointestinal tract. This study investigated the apoptotic effect of ip administered MCLR over time on the duodenum, jejenum and ileum of mice receiving a single 75% LD(50) dose. The apoptotic index was significantly raised in all sections at 8 h post exposure (pe) and continued to rise for the 16, 24 and 32 h pe groups, while the glycogen levels were normal at 24 h pe. The duodenum exhibited the most significant increase in apoptotic index overall, followed by the jejenum and ileum. Immunohistochemistry indicated the presence of MCLR in the lamina propria suggesting a role for MCLR in the induction of apoptosis in the GIT of mice exposed to a single sublethal dose of MCLR.

Animals↗

Hereditary multiple atresias of the gastrointestinal tract: report of a case and review of the literature.

Hereditary multiple atresia of the gastrointestinal tract is an extremely rare subgroup of intestinal atresia. The aim of this study was to report a new case, to review the literature, and to describe the unique features of this malformation. A computer-generated list of articles on this subject was obtained, and all articles relative to this malformation were reviewed. Thirty-five other well-documented cases were found in the literature. Hereditary multiple atresias have several unique features: (1) the abdominal x-ray shows signs of gastric or duodenal atresia combined with typical large rounded or oval homogeneous calcifications in the abdominal cavity, (2) intraoperatively widespread atresias (exclusively type I and II) extending mostly from stomach to rectum are found, (3) cystic dilatation of the bile ducts can be present in cases with both complete pyloric and duodenal or proximal jejunal atresia, (4) the pathogenesis is still speculative; a combined immunodeficiency should be excluded, and (5) a fatal outcome is the rule.

Abnormalities, Multiple↗

Tumor stenoses of the upper gastrointestinal tract--therapeutic alternatives to laser therapy.

Alternatives to laser treatment of tumor stenoses of upper gastrointestinal tract include dilatation, implantation of bridging tubes, radiation therapy and chemotherapy. Based on the experience of 170 bridging tubes implanted and laser therapy in 70 patients with tumor stenoses (presented elsewhere) "tubes and laser" are compared. Complication rate, applicability in very proximal and distal stenoses are in favour of laser therapy, costs, hospitalisation time, possibility to occlude fistulae and short recurrence time after laser therapy are facts speaking for oesophageal bridging tubes. The question "tubes or laser" has to be answered by "tubes and laser" already.

Cisplatin↗

[A new possibility in treating stenosing tumors of the upper gastrointestinal tract].

A new method for treating inoperable patients with stenosing malignant tumors of the upper gastrointestinal tract consists in the combination of laser beam followed by direct internal radiation of the tumor using the afterload technique. It brings rapid improvement of dysphagia and resumption of oral feeding. Improvement in quality of life such as this has been achieved in 21 of 24 patients without any signs of complication due to therapy.

Ambulatory Care↗

Applicability of the Ussing chamber technique to permeability determinations in functionally distinct regions of the gastrointestinal tract in the rat.

BACKGROUND: Ussing chambers are commonly utilized for in vitro investigations into gastrointestinal permeability. However, their sensitivity and applicability to the small intestine have not been well characterized. METHODS: In order to investigate the effects of experimentally induced damage and the relative contribution of the mucosa and muscularis externa layers to transmural permeability in the small intestine, stomach and colon, normal rat intestinal tissues were mounted in Ussing chambers with or without removal of the muscularis externa or mucosal layers. Gastric tissues were damaged in vivo by exposure to indomethacin (100 mg kg(-1)), while ileal tissues were damaged in vitro by 0.4 M NaCl. Tissue damage was assessed histologically, while permeability parameters included conductance (G), potential difference (PD) and mucosal to serosal flux of horseradish peroxidase (HRP). RESULTS: Damage localized to the tissue edges (edge damage) accounted for 25%-50% of the exposed epithelial length in the ileum, while less than 20% of stomach and colon epithelium was affected by edge damage. In the damaged stomach, a 20% reduction in epithelialization was accompanied by increases in G (P < 0.001) and HRP (P < 0.01) flux. Removal of the muscularis externa did not affect mucosal viability in the undamaged ileum or colon although HRP flux in the colon, but not ileum, was increased (P < 0.01). Removal of the ileal mucosa produced increases in G and HRP flux, while PD was maintained. CONCLUSION: We conclude that the Ussing chamber technique is suitable for application to studies of gastric and colonic permeability in rats. However, owing to the prevalence and extent of edge damage in the small intestine, we would caution against the use of this technique for permeability studies in this region of the gastrointestinal tract in the rat.

Animals↗

Effect of microflora on the free amino acid distribution in various regions of the mouse gastrointestinal tract.

The distribution of free amino acids in the contents of various regions of the gastrointestinal tract (stomach, upper small intestine, lower small intestine, cecum, upper colon and lower colon) was studied in germfree and conventionalized mice. Particular emphasis was placed on the conversion of tryptophan to indole as a probe for studying intermicrobial interactions and microbe-host interactions in vivo. Great differences were observed in the free amino acid content of the various regions of the digestive tract in each type of mouse and also in any one region between germfree and conventionalized mice. As would be expected, there were fewer differences in amino acid distribution between the types of mice in both regions of the small intestine. This correlates with a much lower population of microorganisms in these regions. The changes in free amino acid content and distribution produced by microflora are great enough to serve as a good probe for studying the interactions of a limited number of species of microbes in gnotobiotic animals and assign possible specific functions to each species.

Amino Acids↗

Growth hormone receptor expression in the rat gastrointestinal tract.

We have used immunohistochemistry to define the cellular distribution of GH receptors in the gastrointestinal tract (GIT) and its derivatives. Immunohistochemistry was performed in the adult rat GIT with a panel of characterized monoclonal antibodies to the GH receptor. The most intense and heterogeneous immunoreactivity was observed in epithelial cell subpopulations of GIT mucosa. Mesenchymal elements of the GIT were homogenously and moderately immunoreactive. Intense immunoreactivity was observed in the ductal epithelium of the sublingual gland, scattered basal epidermal cells of the esophageal mucosa, zymogen cells of the gastric glands, scattered surface epithelial cells of the stomach, and scattered peripheral pancreatic acinar groups. Scattered enteroendocrine cells and parietal cells, crypt and villous columnar cells of the small intestine, surface columnar cells of the cecum/colon, crypt base columnar cells of the colon, and contiguous peripheral cords of pancreatic islet cells displayed strong immunoreactivity. No immunoreactivity was detectable in the mucous and serous acini of the sublingual and submandibular gland, respectively, mucous-secreting cells of the base of the cardiac and pyloric glands, surface epithelial cells of the fundus, paneth cells, goblet cells of cecum/colon, or mucous cells at the base of the cecal crypt. Other elements of the GIT were moderately or weakly immunoreactive. In support of our localization we can detect high affinity binding (Ka = 3 x 10(9] of [125I]human GH with ovine GH as displacing ligand to crude homogenates of adult rat stomach and intestine. We conclude that discrete epithelial cell subpopulations of the GIT and its derivatives are directly responsive to GH action. GH may, therefore, act independently of or synergistically with hepatic insulin-like growth factor-I in executing its physiological and/or growth-promoting role in the GIT.

Animals↗

The role of the liver in translocation of IgA into the gastrointestinal tract.

The liver plays a key role in the translocation of IgA into the upper gastrointestinal tract. The amount of IgA transported and the mechanisms involved, however, vary widely among species. In some, best defined in the rat, large amounts of polymeric IgA (pIgA) are cleared from the plasma by hepatocytes, which synthesize the polymeric immunoglobulin receptor, secretory component (SC), and express it on their sinusoidal plasma membranes. Circulating pIgA binds to SC, is internalized into endocytic vesicles and transported across the hepatocyte to the bile canalicular membrane, where the pIgA is released into bile in complex with a portion of the SC, i.e., secretory sIgA (sIgA). In some other species, including man, there is much less hepatic transport of circulating IgA, at least in part because SC is present only in biliary epithelium, and there is relatively more local synthesis of IgA within hepatobiliary tissues. On the other hand, certain IgA1 myeloma proteins appear to bind to and enter human hepatocytes via an asialoglycoprotein receptor. These species differences have implications for the biological significance of the biliary secretion of IgA, including the disposal of circulating IgA-antigen complexes into bile.

Animals↗