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Substance P and bradykinin stimulate plasma extravasation in the mouse gastrointestinal tract and pancreas.

Neurogenic inflammation is mediated by release of tachykinins from sensory nerves, which stimulate plasma extravasation from postcapillary venules. Because there are conflicting results regarding the importance of neurogenic inflammation in the gastrointestinal tract, we quantified plasma extravasation using Evans blue and identified sites of the leak using Monastral blue in the mouse. Substance P and bradykinin stimulated extravasation from postcapillary venules in the stomach, small and large intestine, pancreas, urinary bladder, trachea, and skin by two- to sevenfold by interacting with NK1 and B2 receptors, respectively. Stimulation of sensory nerves with capsaicin also induced extravasation. Capsaicin- and bradykinin-stimulated extravasation was attenuated by an NK1-receptor antagonist and is thus mediated by release of tachykinins and activation of the NK1 receptor. We conclude that 1) substance P stimulates extravasation in the gastrointestinal tract and pancreas of mice by interacting with the NK1 receptors, and 2) capsaicin and bradykinin induce plasma extravasation by stimulating tachykinin release from sensory nerves. Thus neurogenic mechanisms mediate inflammation in the gastrointestinal tract and pancreas of the mouse.

Animals↗

Prevalence of upper and lower gastrointestinal tract findings in liver transplant candidates undergoing screening endoscopic evaluation.

OBJECTIVE: The incidence of esophageal and gastric varices and portal hypertensive gastropathy (PHG) has been well studied in cirrhotic patients. Because little is known of the prevalence of other upper and lower gastrointestinal tract pathology in pre-liver transplant candidates, we retrospectively studied the prevalence of and factors associated with these findings. METHODS: One hundred and twenty pre-liver transplant candidates underwent esophagogastroduodenoscopy to evaluate for varices, and 71 of them also underwent flexible sigmoidoscopy to screen for colorectal carcinoma. The association of upper and lower GI tract pathology with Child-Pugh Class, etiology of cirrhosis, and signs of portal hypertension, including presence and size of esophageal varices, presence of gastric varices, PHG, ascites, and splenomegaly, was analyzed using univariate and multivariate analysis. RESULTS: Etiology of cirrhosis among 87 men and 33 women (mean age, 52 yr) included 25% hepatitis C, 27% hepatitis C/alcohol, 15% alcohol, 10% primary sclerosing cholangitis/primary biliary cirrhosis, 9% cryptogenic, 8% metabolic, and 6% hepatitis B. Prevalence of Child-Pugh Classes A, B, and C were 34%, 49%, and 17%, respectively; 73% of patients had esophageal varices (23% were large), 62% PHG (23% were severe), and 16% gastric varices. Excluding varices and PHG, endoscopic findings in the upper GI tract (n = 120) included: 13% esophagitis/ulcers, 7.5% gastritis, 8% duodenitis, 2% Barrett's esophagus, 3% duodenal ulcers, and 2% gastric ulcers. Findings in the lower gastrointestinal tract (n = 71) included 21% adenomatous polyps, 21% internal hemorrhoids, 15% diverticulosis, 7% rectal varices, 3% colopathy, and 3% vascular ectasias. Univariate analysis revealed that there was a significant association between rectal varices and severe PHG (p < 0.05). This association was not maintained when multivariate analysis was performed. CONCLUSIONS: Among all the findings, only rectal varices and colopathy were of higher prevalence in the pre-liver transplant population than that reported for the general population. No significant associations were found between these gastrointestinal tract lesions and patient characteristics.

Colorectal Neoplasms↗

Intravenous ribavirin for eradication of respiratory syncytial virus (RSV) and adenovirus isolates from the respiratory and/or gastrointestinal tract in recipients of allogeneic hematopoietic stem cell transplants.

In a retrospective analysis, we identified 38 evaluable patients who received intravenous ribavirin after adenovirus or RSV detection in the respiratory and/or gastrointestinal tract throughout the years 1998 and 2001. A total of 43 treatment cycles are analyzed. Intravenous ribavirin was combined with cidofovir in about half of the patients. In six out of eight patients treated because of RSV isolates from the respiratory tract, the virus was no longer detectable after treatment. In case of adenovirus isolates, the treatment was efficacious in eradicating the virus from the respiratory tract in more than 60% and from the gastrointestinal tract in 75% of treatment cycles. The addition of cidofovir was not beneficial in eradicating RSV isolates, but somewhat improved the virus clearance of adenovirus. Virus clearance was associated with a trend to a better median survival after virus detection. There were some episodes of suspected hemolysis and a trend towards lower leukocyte counts, reaching grade 3 toxicity in about 15% of treatment cycles. However, in general, intravenous ribavirin was well tolerated. In conclusion, the possible efficacy of intravenous Ribavirin in controlling RSV or adenovirus infections after allogeneic stem cell transplantations should be evaluated in prospective clinical trials.

Adenoviridae↗

[Emergency endoscopy in upper gastrointestinal tract hemorrhages].

The urgent endoscopy of the superior gastrointestinal haemorrhage carefully and quickly helps in clarifying the following questions: Is the patient going on bleeding? Is conservative approach allowed? Must be operated? It is without danger in the hand of the experienced. In 95.20% we could get a positive evidence. In this the advantage compared with other methods is shown. The examination should possibly be done only by means of a glass fibre endoscope and may be performed only after combat against shock. It is reported on own results of 125 endoscopies in haemorrhage of the superior gastrointestinal tract.

Emergencies↗

An immunohistochemical study of interstitial cells of Cajal (ICC) in the equine gastrointestinal tract.

The interstitial cells of Cajal (ICC) are c-kit immunoreactive cells of the gastrointestinal tract which are suggested to have a role in the control of intestinal motility. Cells with c-kit immunoreactivity have not been previously described in the gastrointestinal tract of the horse. Immunoreactivity for c-kit was revealed using immunohistochemical labelling with an anti-c-kit polyclonal antibody. Sections of normal gastrointestinal tissue were examined from 13 anatomically defined sites from stomach to small colon taken from horses free from gastrointestinal disease. Three types of c-kit immunoreactive cells were identified: spindle-shaped cells in the region of the myenteric plexus, stellate or bipolar cells in the circular muscle layer, and round cells in the submucosa. The round cells were shown to be mast cells with the use of toluidine blue staining, whereas the other c-kit immunoreactive cells did not exhibit metachromasia and were classified as ICC. This study will serve as a basis for future pathological studies in the horse.

Animals↗

[Endocrine system of the gastrointestinal tract. Pathophysiology with a clinical view].

Present role of the hormones produced in the gastrointestinal tract is shown in this short overview. Selected actual information on glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1) and somatostatin is presented as an example in development of the knowledge of pathophysiology and of the possibilities in their clinical use. It is evident that hormones originating from the gastrointestinal tract are perspective not only in relationship to the explanation of pathophysiology of different diseases but they may be used more for diagnostic and therapeutic purposes.

Digestive System Physiological Phenomena↗

Expression, regulation and the role of SLC26 Cl-/HCO3- exchangers in kidney and gastrointestinal tract.

SLC26 isoforms are members of a large, conserved family of anion exchangers that display highly restricted and distinct tissue distribution. Cloning experiments have identified the existence of 10 SLC26 genes or isoforms (SLC26A1-11). The products of all, excepting SLC26A5 (prestin), function as anion exchangers with versatility with respect to transported anions. Modes of transport mediated by SLC26 members include the exchange of chloride for bicarbonate, hydroxyl, sulfate, formate, iodide, or oxalate with variable specificity. Several members of SLC26 family mediate chloride-bicarbonate exchange and display expression in a limited number of tissues including the gastrointestinal tract and/or kidney, with distinct subcellular (apical or basolateral) localization. These include SLC26A3 (DRA), SLC26A4 (pendrin), SLC26A6 (PAT1 or CFEX), SLC26A7 and SLC26A9. SLC26A3 and A9 are not expressed in the kidney but SLC26A4, A6 and A7 are. Genetically engineered null mice have highlighted the important role of two members of the SLC26 family, SLC26A4 and SLC26A6, in homeostatic function in kidney and/or intestine. In conjunction with expression studies, the evolving picture points to important roles for SLC26 family in chloride, bicarbonate, oxalate or sulfate transport and homeostasis in gastrointestinal tract, kidney and several other tissues. This review in particular focuses on the role and regulation of SLC26A6, A7 and A9 in the kidney and/or gastrointestinal tract.

Animals↗

[Endoscopic ultrasonography and diagnostic algorithms in diseases of the gastrointestinal tract].

This article reviews the recent literature on the role of endoscopic ultrasonography (EUS) as diagnostic and therapeutic tool, defines its place in the algorithm of diagnostic procedures and informs how to treat some patients evaluated by EUS. Endoscopic ultrasonography utilizes the technology of endoscopy to introduce high frequency ultrasound probes in the upper or lower part of gastrointestinal tract to visualize gastrointestinal wall and adjacent structures. This method has come out as an important modality for the diagnosis and staging of benign and malignant lesions of the gut wall and surrounding structures of the mediastinum, abdomen and pelvis. It is also used as a diagnostic tool for the evaluation of submucosal masses of the upper gastrointestinal tract and the rectosigmoid, for locating pancreatic endocrine tumors, and for the assessment of vascular disease. Interventional applications, such as EUS-guided fine-needle aspiration (EUS-FNA) for obtaining tissue/fluid samples, for pseudocyst drainage, and also for delivery of local therapy will likely enhance the clinical utility and cost-effectiveness of this imaging modality. The widest application of EUS is, however, in the diagnosis and staging of esophageal, gastric, rectal, and pancreaticobiliary carcinoma. EUS has been shown to change the approach to clinical management in a significant proportion of patients to a less costly, risky, or invasive strategy.

Digestive System↗

[The adhesive properties of lactobacteria and escherichiae in different divisions of human gastrointestinal tract under normal and pathologic conditions].

A comparison of the adhesive properties of lactobacteria and escherichiae in different divisions of human gastrointestinal tract under normal and pathologic conditions was conducted. The study shows that the population changeability of the adhesive properties of lactobacteria and escherichiae is determined by localization of the strain in the gastrointestinal tract, and morphofunctional condition of the intestinal wall. Bacteria's adhesiveness to glycocalix of intestinal epithelial cells is higher in the left half of the colon than in the right one, and is still higher in feces. Their co-adhesiveness changes in the reverse order. Bacteria localized in the parietal mucin of inflamed segments, possess low capability of forming microcolonies, and high adhesiveness to glycocalix. The results of the study demonstrate that the choice of therapeutic probiotic bacterial strains should depend on the anatomic localization of the lesion and the character of gastrointestinal pathology.

Adult↗

Iron deficiency anemia in the elderly: prevalence and endoscopic evaluation of the gastrointestinal tract in outpatients.

Iron deficiency anemia (IDA), mostly due to chronic occult bleeding from the gastrointestinal tract, is a common problem in the elderly. This study aimed to determine the prevalence of IDA in the elderly and to investigate the gastrointestinal tract in elderly patients with IDA. 1,388 patients over 65 years were prospectively evaluated for IDA in our outpatient clinic. IDA was defined if decreased hemoglobin concentrations (<13 g/dl for men and <12 g/dl for women) were associated with low serum ferritin levels (<15 ng/ml in men and <9 ng/ml in women). We evaluated the gastrointestinal system of all patients with IDA by upper gastrointestinal endoscopy and colonoscopy regardless of fecal occult blood loss. The prevalence of anemia was found to be 25% (n = 347) in our study population, and 30.5% (n = 106) of these patients with anemia had iron deficiency. Upper gastrointestinal endoscopy and colonoscopy were performed in 96 patients with IDA. Fifty-eight upper gastrointestinal system lesions (55 patients, 57.3%) and 27 colonic lesions (26 patients, 27.1%) were detected. We diagnosed gastrointestinal malignancy in 15 (15.6%) elderly patients with IDA (8 colon, 1 esophageal and 6 gastric cancers). IDA is a common problem in elderly patients; consequently, before iron replacement therapy, patients should be thoroughly investigated regarding a possible association with gastrointestinal malignancy.

Aged↗

Malignant lymphoma of the gastrointestinal tract. Erskine Memorial Lecture, 1979.

This paper reviews the literature concerning malignant lymphoma of the gastrointestinal tract. The diagnosis, pattern of dissemination, histologic data, prognosis, and results of treatment are discussed. The results suggest that localized lymphoma of the gastrointestinal tract is compatible with long-term survival and possible cure. A more careful look at the staging of the disease is warranted, as well as the development of appropriate programs of surgery, chemotherapy, and radiotherapy to maximize the potential for control of the disease while minimizing damage to normal tissue.

Adolescent↗

P2X(2) purine receptor immunoreactivity of intraganglionic laminar endings in the mouse gastrointestinal tract.

The distribution of P2X(2) purine receptor subunit immunoreactivity has been investigated in the mouse gastrointestinal tract. Immunoreactivity occurred in intraganglionic laminar endings (IGLEs) associated with myenteric ganglia throughout the gastrointestinal tract. In the esophagus, IGLEs supplied every myenteric ganglion. The proportion of ganglia supplied decreased from 85% in the stomach to 10% in the ileum, and from 50% in the caecum to 15% in the distal colon. There was substantial loss of IGLEs from myenteric ganglia of all abdominal regions after bilateral subdiaphragmatic section of the vagus nerves. IGLEs in the esophagus consisted of dense clusters of punctate immunoreactive varicosities. In the stomach and duodenum they had prominent lamellar processes and irregular, but smaller, lamellae were found in other regions. Rare immunoreactive IGLEs occurred in the submucosa of the distal colon. P2X(2) receptor immunoreactivity was on the surfaces and in the cytoplasm of a minority of nerve cells in myenteric ganglia. It is concluded that P2X(2) purine receptor immunoreactivity is a feature of IGLEs in the mouse, and that P2X receptor agonists may modulate sensitivity of the IGLEs.

Animals↗

Meal-stimulated and atropine-inhibited secretion of pancreatic polypeptide in healthy subjects, members of MEA I families and patients with malignant endocrine tumours of the gastrointestinal tract.

Pancreatic polypeptide has been suggested as a marker for endocrine malignancies of the gastrointestinal tract. However, the secretion of PP shows great intra- and inter-individual variation, causing both false negative and positive results. In order to reduce these risks, we have evaluated a new combined stimulatory and inhibitory test of PP secretion. Six healthy subjects, 23 members of three MEA I families, seven patients with malignant pancreatic endocrine tumours and four patients with carcinoid tumours of the gastrointestinal tract were subjected to a standardized test meal, followed by intravenous atropine 60 min after the start of the meal. Serum PP was monitored during 2 h. In healthy subjects the meal caused a rapid increase in serum PP within 20 min and intravenous atropine caused a significant (P less than 0.05) decrease of serum PP within 15 min. Patients with malignant endocrine pancreatic tumours or carcinoids had a delayed response after the test meal, with maximum levels at 45 min, but still with a significant inhibition by atropine. Even tumour patients with initially normal or slightly increased basal PP levels showed this secretion pattern. Healthy members of MEA I families displayed identical PP curves to healthy subjects, whereas members with elevated basal PP levels who had been previously affected by hyperparathyroidism and/or prolactinomas showed similar secretion patterns to pancreatic tumour patients. We think that a meal stimulatory test is of great value in the diagnosis of gastrointestinal endocrine tumours and also in the identification of subjects with the MEA I trait, who are at high risk of having pancreatic endocrine tumours.

Adolescent↗

Effects of protein restriction in early life on growth and function of the gastrointestinal tract of the rat.

BACKGROUND: Undernutrition during early life may have both immediate and later consequences. This study was undertaken to measure the long-term effects of perinatal undernutrition on the growth and function of the gastrointestinal tract. METHODS: Pregnant rats were assigned to one of four groups that received isocaloric diets restricted in protein during pregnancy or lactation and during both or neither. Thereafter, their pups were followed until aged 1 year. RESULTS: At 21 days the body weights of the young of those born of dams with postnatal protein restriction were halved, with comparable reductions in the weights of the stomach and caecum, compared with those of control animals. The lengths of the small and large intestines and mucosal weights of the foregut were also significantly reduced. Lactase activities were significantly increased and sucrase and maltase activities significantly reduced. By 42 days all the effects were less marked, and at 1 year the dimensions of the organs of the gastrointestinal tract and the composition and enzyme levels of the mucosa were all insignificantly different relative to body weight. CONCLUSIONS: Prenatal protein restriction alone had no significant long-term negative effects on body weight, growth, or mucosal hydrolase activity of the gastrointestinal tract. Postnatal protein restriction had a marked effect on these indices in early life and delayed the changes in mucosal hydrolases usually seen at weaning. In contrast with other organs and their functions, long-term growth of the gut and activity of small intestinal hydrolases are preserved in the face of perinatal protein restriction.

Animals↗

Leptin, leptin receptors and ACTH immunoreactivities are present in the gastrointestinal tract and the neural tube of tadpoles of the newt Triturus.

Leptin, its receptor and ACTH were detected by immunohistochemistry in the gastrointestinal tract and the neural tube of the amphibian urodele, Triturus cristatus carnifex, during development. These molecules were found after hatching of tadpoles, starting from stage 41. In the gastrointestinal tract, cells immunoreactive to leptin and its receptor were first revealed in the stomach, the liver and the gut and then in the pancreas. Both immunoreactives were colocalized in the same cells in some areas. Immunostaining for ACTH appeared at stages 43/45 in the stomach, the gut and the pancreas. In adjacent sections, a few cells immunoreactive to both ACTH and leptin receptor were detected. A few cells were immunoreactive to both insulin and leptin receptor. Immunoreactivities to leptin and its receptor were also found in adjacent sections of the neural tube, often colocalized in the same cell. Moreover, in prosencephalon, mesencephalon, rhomboencephalon and spinal cord, ACTH-immunoreactive cells were detected in the same areas as the leptin receptor immunoreactive cells. These results suggest the existence of a neuroendocrine network in newt tadpoles both at the central level, where it resembles that of mammals, and at the peripheral level, where it may act locally to regulate food intake and metabolism, e.g. yolk digestion.

Adrenocorticotropic Hormone↗

Altered mucin expression in the gastrointestinal tract: a review.

Early studies of changes in mucin expression in disorders of the gastrointestinal tract focused on alterations in the carbohydrate chain. This review briefly considers the various mechanisms by which such alterations may come about: (a) normal variation, (b) sialic acid alterations, (c) defective assembly of carbohydrate side-chains, (d) changed expression of core proteins and (e) epithelial metaplasia. The availability of monoclonal antibodies to mucin core proteins adds a new dimension to mucin histochemistry. It is now possible to offer explanations for traditional mucin histochemical findings on the basis of lineage-specific patterns of mucin core protein expression. Changes in core protein expression are described in inflammatory, metaplastic and neoplastic disorders of the gastrointestinal tract. The possibility that mucin change could be important in the aetiology of some diseases such as ulcerative colitis and H. pylori gastritis is considered. It is more probable, however, that changes in mucin expression are secondary to reprogramming of cellular differentiation and altered cell turnover. As such they may serve as markers to explain pathogenesis and provide novel diagnostic and prognostic information.

Cell Differentiation↗

T-bet and mucosal Th1 responses in the gastrointestinal tract.

T cells play an essential role in regulating mucosal immune responses in the gastrointestinal tract. Recent observations on T helper cell differentiation and activation by regulatory transcription factors-especially T-bet-in chronic inflammatory diseases have provided new perspectives for understanding mucosal immunity. Here we summarise recent advances in the field of transcription factors and discuss the implications of these findings for future therapeutic approaches in inflammatory bowel diseases. In particular, we have focused on the role of T-bet in controlling mucosal Th1 responses in the gastrointestinal tract.

Animals↗

Activation of NF-kappaB varies in different regions of the gastrointestinal tract during endotoxemia.

The transcription nuclear factor-kappaB (NF-kappaB) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-kappaB is activated in the jejunal mucosa during endotoxemia, but the response of NF-kappaB in other parts of the gastrointestinal tract is not known. We hypothesized that NF-kappaB is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay in mucosa of the stomach, jejunum, ileum, and colon from endotoxemic and saline-injected mice. Cytoplasmic levels of the NF-kappaB inhibitory proteins IkappaB-alpha and IkappaB-beta were determined by Western blot analysis. Endotoxemia increased NF-kappaB activity in mucosa of stomach, jejunum, and ileum, with jejunum responding to smaller doses of endotoxin than the other parts of the gastrointestinal tract. NF-kappaB DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin. IkappaB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-kappaB. The results suggest that during endotoxemia, NF-kappaB is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.

Animals↗