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[Characteristics of oxidative metabolism of the gastrointestinal tract during adaptation of the rat to high temperatures].

Dynamic alterations in total respiratory metabolism, tissue respiration in various parts of gastrointestinal tract, respiratory and phosphorylating activity in mitochondria isolated from small intestinal mucosa were studied in rats, maintained during 30 days under conditions of high environmental temperature. Moderately high temperature caused a distinct redistribution of functional activity among various parts of gastrointestinal tract. A decrease in total respiratory metabolism occurred partially due to a decrease in tissue respiration, suggesting various role of these tissues in total body metabolism. Mitochondrial oxidation changed from alpha-ketoglutarate to succinate pathway depending on duration of the heat treatment. Higher temperatures caused a decrease in the mitochondrial respiration rate uncoupling of oxidative phosphorylation.

Acclimatization↗

Endogenous prostaglandins and microflora modulate DNA synthesis and neuroendocrine peptides in the rat gastrointestinal tract.

BACKGROUND: Previous studies suggest that E2 prostaglandins and the microflora may participate in the regulation of endocrine cells and of gastrointestinal cell kinetics. Our aim is to examine the actions of endogenous prostaglandins and of the microflora on gastrointestinal cell proliferation and tissue levels of neuroendocrine peptides. METHODS: Germfree and ex-germfree rats were treated with subcutaneous placebo or 1.5 mg/kg indomethacin for 3 days. All rats were labeled with 3H-methyl-thymidine, and biopsy specimens from different parts of the gastrointestinal tract were processed for autoradiography. DNA synthesis was estimated by the labeling index, except in the oxyntic mucosa, where the total number of labeled cells present in 7.5 mm mucosa was used. The concentration of neuroendocrine peptides was determined by radioimmunoassay. RESULTS: In the germfree rat, indomethacin reduced DNA synthesis in the fundus, duodenum, and proximal jejunum (P < 0.05) and the number of villous cells throughout the small intestine (P < 0.05). Exposure to microflora increased DNA synthesis in the proximal and distal jejunum, ileum, and colon (P < 0.05 versus germfree controls) and the number of crypt cells in the distal small intestine and colon (P < 0.05) and reduced the number of villous cells in the small intestine (P < 0.05) but did not affect tissue concentrations of neuroendocrine peptides. Indomethacin increased the concentration of somatostatin in the stomach, duodenum, and colon of germfree rats (P < 0.001), the concentration of calcitonin gene-related peptide (CGRP) and enteroglucagon in the proximal and distal jejunum and ileum (P < 0.001), and the concentration of glucagon in the colon (P < 0.05). The concentrations of somatostatin, CGRP, and glucagon were lower in indomethacin-treated ex-germfree rats than in indomethacin-treated germfree rats (P < 0.01). CONCLUSIONS: Indomethacin selectively reduced DNA synthesis in the upper gastrointestinal tract of germfree rats, indicating a basal stimulatory role for endogenous prostaglandins on cell proliferation. Endogenous prostaglandins modulate synthesis or release of gastrointestinal neuroendocrine peptides. Somatostatin may mediate indomethacin-induced reduction of DNA synthesis. The microflora stimulates cell proliferation and influences tissue levels of neuroendocrine peptides in a manner opposite to that of indomethacin.

Animals↗

Sensitization of rat gastrointestinal tract to acetylcholine and histamine produced by X-radiation.

Abdominal x-radiation produces both acute and chronic disturbances of gastrointestinal motility. Anaesthetized Albino-Oxford rats received one-session x-radiation (absorbed dose 10 Gy) of whole abdomen. Two hours after irradiation the rats were sacrificed and segments of their gastrointestinal tract (gastric fundus, jejunum, ileum and ascending colon, were mounted in isolated organ bath. Acetylcholine and 5-hydroxytryptamine produced tonic contractions of all gut segments, while histamine did so only with gastric fundus. While contractile effect of 5-hydroxytryptamine was not affected by x-radiation, the responses of all gut segments on acetylcholine were potentiated and shifted towards lower concentrations. After x-radiation histamine produced concentration-dependent tonic contraction of previously unresponsive jejunum and ascending colon. The results of our study suggest that x-radiation produces acute sensitization of rat gastrointestinal tract to acetylcholine and histamine.

Acetylcholine↗

Study of acute localised inflammation of the gastrointestinal tract: the effluent lymph.

The effect of localised acute inflammation, produced by a small intestinal anastomosis on the effluent lymph of the gastrointestinal tract and on the efferent lymph of the mesenteric lymph glands has been studied in rats. There is a progressive increase in the output of lymph from the gastrointestinal tract in rats with an intact anastomosis, but a decreased output in animals with a disrupted anastomosis causing either generalised peritonitis or a localised para-anastomotic abscess. The total white cell output is increased on the second day after constructing an intact intestinal anastomosis and this increase is principally due to neutrophil polymorphonuclear leucocytes. The neutrophil polymorphonuclear leucocyte response is prolonged, but has returned to normal values at four weeks. Although the output of cells of the mononuclear phagocytic series which are esterase positive is increased it is not statistically significant. An intact anastomosis does not produce any alteration in the lymphocyte output. The neutrophil polymorphonuclear leucocyte response to an intestinal anastomosis is decreased by a factor of two and the non-lymphocytic non-specific esterase positive cell response is decreased by a factor of six by the mesenteric lymph glands which may be functioning in a 'filtering' capacity dealing with agents originating at the anastomosis and noxious to the body,

Animals↗

Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s.

BACKGROUND: In the last decades, studies have estimated the upper gastrointestinal tract bleeding/perforation (UGIB) risk associated with individual nonsteroidal anti-inflammatory drugs (NSAIDs). Later analyses have also included the effect of patterns of NSAID use, risk factors for UGIB, and modifiers of NSAID effect. METHODS: Systematic review of case-control and cohort studies on serious gastrointestinal tract complications and nonaspirin NSAIDs published between 1990 and 1999 using MEDLINE. Eighteen original studies were selected according to predefined criteria. Two researchers extracted the data independently. Pooled relative risk estimates were calculated according to subject and exposure characteristics. Heterogeneity of effects was tested and reasons for heterogeneity were considered. RESULTS: Advanced age, history of peptic ulcer disease, and being male were risk factors for UGIB. Nonsteroidal anti-inflammatory drug users with advanced age or a history of peptic ulcer had the highest absolute risks. The pooled relative risk of UGIB after exposure to NSAIDs was 3.8 (95% confidence interval, 3.6-4.1). The increased risk was maintained during treatment and returned to baseline once treatment was stopped. A clear dose response was observed. There was some variation in risk between individual NSAIDs, though these differences were markedly attenuated when comparable daily doses were considered. CONCLUSIONS: The elderly and patients with a history of peptic ulcer could benefit the most from a reduction in NSAID gastrotoxicity. Whenever possible, physicians may wish to recommend lower doses to reduce the UGIB risk associated with all individual NSAIDs, especially in the subgroup of patients with the greatest background risk.

Age Factors↗

Multiple lymphomatous polyposis of the gastrointestinal tract. A clinicopathologically distinctive form of non-Hodgkin's lymphoma of B-cell centrocytic type.

Multiple lymphomatous polyposis of the gastrointestinal tract was initially described as mucosal lymphomatous involvement by any of a variety of Hodgkin's or non-Hodgkin's lymphomas that produced a polypoid appearance over long segments of the gastrointestinal tract. We studied four patients in whom histology revealed diffuse small cleaved cell lymphoma (one case), or intermediate lymphocytic lymphoma of diffuse type (one case), or mantle zone pattern (two cases). All four cases are classifiable as centrocytic lymphoma. Cell suspension and immunocytochemical studies demonstrated B-cells of IgMD or M type with light chain restriction (two kappa, two lambda) showing a B1+ HLA Dr+ LN2+ CD5+ CD10+. Although all four patients had a partial response to combination chemotherapy, three of them died within 3 years. Analysis of 24 cases reported since 1971 (including the present cases) suggests that MLP is a distinct clinicopathological entity that results from gastrointestinal involvement by a B-cell centrocytic lymphoma. It is distinct from the recently described clinicopathological forms of centrocytic lymphoma and intermediate lymphocytic lymphoma, which both show extensive peripheral lymphadenopathy and splenomegaly, but it is probably closely related to them. The differences are probably attributable to distinct cell tropism or homing properties rather than to cellular histogenesis or degree of maturation.

Aged↗

Taste receptors in the gastrointestinal tract. II. L-amino acid sensing by calcium-sensing receptors: implications for GI physiology.

The extracellular calcium-sensing receptor (CaR) is a multimodal sensor for several key nutrients, notably Ca2+ ions and L-amino acids, and is expressed abundantly throughout the gastrointestinal tract. While its role as a Ca2+ ion sensor is well recognized, its physiological significance as an L-amino acid sensor and thus, in the gastrointestinal tract, as a sensor of protein ingestion is only now coming to light. This review focuses on the CaR's amino acid sensing properties at both the molecular and cellular levels and considers new and putative physiological roles for the CaR in the amino acid-dependent regulation of gut hormone secretion, epithelial transport, and satiety.

Amino Acids↗

Distribution of immunoreactive vasotocin and mesotocin in the chicken gastrointestinal tract.

Immunoreactive arginine vasotocin (AVT) and mesotocin (MT) were measured in heart, breast muscle, adrenals, testes, and different parts of the gastrointestinal tract in adult male chickens. Neither of the peptides were detected in liver, testis, heart and breast muscle. The amounts of AVT and MT in the adrenals were 167 +/- 25 and 669 +/- 198 pg/gland, respectively. Considerable amounts of immunoreactive peptides were found in the gastrointestinal tract with the highest concentration in the proventriculus (4.18 +/- 0.31 ng AVT and 16.58 +/- 0.86 ng MT per organ). Dose-response curves of duodenal and proventriculus extracts were parallel with synthetic AVT and MT standards.

Animals↗

Carcinoid tumours in the gastrointestinal tract--a population-based study from Western Norway.

OBJECTIVE: To analyze population-based incidence, anatomic distribution and patient characteristics of gastrointestinal carcinoid tumours. BACKGROUND: Neuroendocrine carcinomas (NE, carcinoid tumours) arise from neuroendocrine cells and are most commonly found in gastrointestinal tract and lungs. Previous studies on carcinoids report varying incidence rates, location of tumours and patient survival rates. METHODS: Retrospective study. 88 patients were diagnosed with carcinoids located in the gastrointestinal tract in the period 1983-2003 in the Norwegian counties Hordaland and Sogn og Fjordane. Patient and tumour characteristics, treatment and survival were analyzed in a sub-group of 51 patients treated at Haukeland University Hospital. RESULTS: Incidence of carcinoids was 0.8 when analyzed from the counties Hordaland and Sogn og Fjordane as well as when analyzed from Haukeland University Hospital. There were 26 men and 25 women. Median age at surgery was 61 years (range 17-87 years). The tumours were located in the small bowel in 53%, appendix 18%, colon 4%, rectum 4%, stomach 8% and duodenum 10%. Five-year survival rate was 50% in stomach, 80% in duodenum, 43% in the small bowel, 100% for tumours in appendix, 40% in colon and 100% in rectum. CONCLUSION: Carcinoid tumours are relatively uncommon neoplasms and most of them are found in the small bowel. Carcinoids in the ileum tend to be more aggressive and carry a poorer prognosis than carcinoids at other locations. Tumours in the appendix are found at lower age and in an early stage. They rarely metastasize and have an excellent prognosis.

Adolescent↗

Infection of gastrointestinal tract macrophages by HIV-1.

As the largest lymphoid organ and the largest reservoir of macrophages in the body, the gastrointestinal tract mucosa is probably the largest organ reservoir of macrophages infected with HIV-1. To elucidate the biology of HIV-1 infection of intestinal macrophages, we isolated lamina propria macrophages from normal human jejunum by neutral protease digestion, purified the cells by counterflow centrifugal elutriation, and then infected the cells with HIV-1. The lamina propria macrophages were permissive to macrophagetropic isolates of HIV-1 and substantially less permissive to lymphocyte-tropic isolates. Compared with blood monocytes, mucosal macrophages produced 2-3 logs less p24 antigen at peak infection. The reduced level of infection was not due to impaired macrophage viability, reduced CD4 expression, or the isolation procedure. These results confirm that macrophages isolated from the gastrointestinal tract mucosa can support HIV-1 production, albeit at a lower level than blood monocytes. The reduced level of virus production may reflect the unique biology of intestinal lamina propria macrophages.

Antigens, CD↗

Biological effects of epidermal growth factor, with emphasis on the gastrointestinal tract and liver: an update.

Epidermal growth factor (EGF) is a 6,000 Da polypeptide hormone produced by glands of the gastrointestinal tract, namely the salivary and Brunner's glands. It is found in a wide variety of external secretions as well as in blood and amniotic fluid. In fetal and neonatal life, EGF appears to play an important role in the development of the oral cavity, lungs, gastrointestinal tract and eyelids. Its presence in cells of the central nervous system suggests that it also plays a role in modulating the development of this system. In adult animals, the function of EGF is much less well understood. In rodents, it apparently modulates acid secretion from parietal cells in the stomach, and it undoubtedly plays an important role in wound healing, either through its localization within skin or by the licking of wounds with EGF-containing saliva. Considerable evidence now suggests that it may be one of the key factors in initiating liver regeneration after partial hepatectomy or chemical injury. The liver appears to be the principal organ which regulates the circulating level of EGF. In fact, EGF is cleared so efficiently by the liver that only the peripheral cells of the lobule (zone 1) sequester EGF, and little remains in the circulation for cells in the more distal zones (zones 2 and 3). In the liver, EGF normally binds to a plasma membrane receptor and is internalized within the liver cell, where the vast majority of EGF and its receptor are destroyed in lysosomes. A small but consistent quantity of EGF enters the bile intact. In the regenerating liver, however, the lysosomal pathway appears to be shut down, and the EGF is diverted to hepatocyte nuclei prior to the initiation of DNA synthesis. Nuclear EGF is found free as well as bound to a high-molecular-weight protein which has many characteristics identical to the plasma membrane EGF receptor. The plasma membrane receptor is a large transmembrane glycoprotein of 170,000 Da containing four domains: an extracellular EGF-binding portion, a hydrophobic membrane-spanning segment, a proximal cytoplasmic domain which binds ATP and protein substrates containing tyrosine for phosphorylation and a terminal cytoplasmic portion with 3 tyrosines which undergo autophosphorylation after EGF binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Technology insight: Laser-scanning confocal microscopy and endocytoscopy for cellular observation of the gastrointestinal tract.

Recent advances in endoscopic imaging technology have enabled the visualization of early-stage cancer and its precursors in the gastrointestinal tract. Chromoendoscopy, magnifying endoscopy, endoscopic optical coherent tomography, spectroscopy, and various combinations of these technologies, are all important for the recognition of small and unclear lesions. To observe cancer cells in vivo, two types of ultra-high magnifying endoscope--'laser-scanning confocal endoscopy series' and 'contact endoscopy series'--that have a maximum of more than 1,000x magnifying power have been developed. These endoscopes can generate high-quality images of both living cancer cells and normal cells in the gastrointestinal tract, with a quality comparable to that possible with conventional cytology. These novel imaging technologies may make in vivo histological diagnosis by virtual histology possible.

Endoscopy, Gastrointestinal↗

Quantitative detection of Clostridium perfringens in the broiler fowl gastrointestinal tract by real-time PCR.

Strains of Clostridium perfringens are a frequent cause of food-borne disease and gas gangrene and are also associated with necrotic enteritis in chickens. To detect and quantify the levels of C. perfringens in the chicken gastrointestinal tract, a quantitative real-time PCR assay utilizing a fluorogenic, hydrolysis-type probe was developed and utilized to assay material retrieved from the broiler chicken cecum and ileum. Primers and probe were selected following an alignment of 16S rDNA sequences from members of cluster I of the genus Clostridium, and proved to be specific for C. perfringens. The assay could detect approximately 50 fg of C. perfringens genomic DNA and approximately 20 cells in pure culture. Measurements of the analytical sensitivity determined with spiked intestinal contents indicated that the consistent limit of detection with ileal samples was approximately 10(2) CFU/g of ileal material, but only about 10(4) CFU/g of cecal samples. The decreased sensitivity with the cecal samples was due to the presence of an unidentified chemical PCR inhibitor(s) in the cecal DNA purifications. The assay was utilized to rapidly detect and quantify C. perfringens levels in the gut tract of broiler chickens reared without supplementary growth-promoting antibiotics that manifested symptoms of necrotic enteritis. The results illustrated that quantitative real-time PCR correlates well with quantification via standard plate counts in samples taken from the ileal region of the gastrointestinal tract.

Animals↗

Histochemical localization of copper in the gastrointestinal tract of the rat.

Three histochemical reactions for the localization of copper were applied to liver and different parts of the gastrointestinal tract of normal as well as of rats poisoned with a solution of copper. Variable quantities of copper were demonstrated in the livers of all the poisoned rats and in 21 out of 24 sections of jejunum. Rubeanic acid counterstained with 0.5% Cresyl violet gave the best results. Copper was not demonstrable in the livers or the gastrointestinal tract of normal rats. As the metal was concentrated in the upper jejunum, it is likely that this is the site of absorption. Detection of this metal may assist in the diagnosis of hepatolenticular degeneration.

Animals↗

Pharmacodynamic effects of Sandostatin in the gastrointestinal tract.

Somatostatin is widely distributed throughout the human gastrointestinal system. There it is found in neurons and fibers of both the submucosal and the myenteric plexus and the pancreas as well as in the D cells of the stomach, gut and pancreatic islets. Whereas in the intestinal nervous system, in the duodenum and the pancreas, somatostatin-14 appears to be the predominant molecular form, the endocrine-type D cells of the intestine primarily contain somatostatin-28. Somatostatin peptides may act very differently at different sites, as hormones, as paracrine substances or neurotransmitters. Because of this complexity of action, very little is known about the physiological effects of somatostatin in the gastrointestinal tract. In contrast, the pharmacological actions of natural synthetic somatostatin have been thoroughly studied and have given rise to many therapeutic applications. Octreotide, an analogue with a longer half-life and higher potency, has greatly facilitated the clinical application of somatostatin. This review deals with the pharmacological effects of octreotide on different gastrointestinal functions. The somatostatin analogue exerts a long-lasting inhibitory action on gastric acid, pancreatic enzyme and bicarbonate secretion as well as on bile flow. It is also able to inhibit stimulated intestinal secretion, the release of neuropeptides from the gut and the pancreas. It can also prolong orocecum transit time and prevent gallbladder contraction. It inhibits absorption of nutrients and exerts inhibitory effects on splanchnic hemodynamics. It is because of these actions that somatostatin has attracted so much attention in the treatment of different gastrointestinal disorders.

Digestive System↗

Galanin receptors in the rat gastrointestinal tract.

Galanin functions are mediated by three distinct G-protein-coupled receptors, galanin receptor 1 (GalR1), GalR2 and GalR3, which activate different intracellular signaling pathways. Here, we quantified mRNA levels of GalR1, GalR2 and GalR3 in the gastrointestinal tract using real time RT-PCR. GalR1 and GalR2 mRNAs were detected in all segments with the highest levels in the large intestine and stomach, respectively. GalR3 mRNA levels were quite low and mostly confined to the colon. We also investigated the effect of galanin 1-16, which has high affinity for GalR1 and GalR2 and low affinity for GalR3 on depolarization-evoked Ca2+ increases in rat cultured myenteric neurons using Ca2+-imaging. Intracellular Ca2+ changes in myenteric neurons were monitored using the Ca2+ sensitive dye, fluo-4, and confocal microscopy. Galanin 1-16 (1 microM) markedly inhibited the K+-evoked Ca2+ increases in myenteric neurons. In summary, the differential distribution of GalRs supports the hypothesis that the complex effects of galanin in the gastrointestinal tract result from the activation of multiple receptor subtypes. Furthermore, this study confirms the presence of functional GalRs and suggests that galanin modulates transmitter release from myenteric neurons through inhibition of voltage-dependent calcium channels involving a G(i/o)-coupled GalR.

Animals↗

Amount and distribution of carbonic anhydrases CA I and CA II in the gastrointestinal tract.

The levels of carbonic anhydrase (CA) activity and the amounts of carbonic anhydrase isoenzyme CA I and CA II proteins in the human gastrointestinal tract were determined by kinetic assays and radioimmunoassays. Cellular distribution of carbonic anhydrase activity in the various segments of the gastrointestinal tract were studied by the histochemical method of Hansson and the distribution of CA I and CA II by an immunohistochemical method. The stomach and the colon showed high carbonic anhydrase activity, the jejunum had intermediate activity, and the ileum had low activity. In the stomach CA II was the dominating isoenzyme, whereas the jejunum and the colon contained considerable amounts of both forms. Small amounts of both isoenzymes were found in the ileum. Carbonic anhydrase II immunofluorescence was demonstrated in the surface epithelium and in the parietal cells of the gastric mucosa, and in the epithelium of the jejunal villi. The surface epithelium of the colon contained both CA I and CA II. Carbonic anhydrase I was found in many superficial capillaries in all regions studied. The histochemical method demonstrated enzyme activity also at the cell membranes of gastric chief cells, intestinal crypt cells, and a subpopulation of ileal surface cells. This probably indicates presence of the membrane-bound isoenzyme CA IV.

Carbonic Anhydrases↗