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Distribution and density of substance P receptors in the feline gastrointestinal tract using autoradiography.

Autoradiography was used to localize and quantify substance P receptors in the feline gastrointestinal tract. The specific binding of 125I-Bolton Hunter substance P was determined in the esophagus, lower esophageal sphincter, antrum, pylorus, duodenum, jejunum, ileum, ileocecal sphincter, and colon. Competitive binding studies indicated that substance P binding sites or NK-1 receptor sites were demonstrated. The concentration of NK-1 receptors was greatest in the distal half of the gastrointestinal tract, with the highest concentrations in the proximal colon. The circular muscle layer contained the greatest amount of substance P binding. The location and density of binding sites for substance P may be important in understanding the relative importance of both the pharmacological responses to this neuropeptide and the immunohistochemical evidence of the peptide at different sites in the intestine.

Animals↗

Molecular ecological analysis of the succession and diversity of sulfate-reducing bacteria in the mouse gastrointestinal tract.

Intestinal sulfate-reducing bacteria (SRB) growth and resultant hydrogen sulfide production may damage the gastrointestinal epithelium and thereby contribute to chronic intestinal disorders. However, the ecology and phylogenetic diversity of intestinal dissimilatory SRB populations are poorly understood, and endogenous or exogenous sources of available sulfate are not well defined. The succession of intestinal SRB was therefore compared in inbred C57BL/6J mice using a PCR-based metabolic molecular ecology (MME) approach that targets a conserved region of subunit A of the adenosine-5'-phosphosulfate (APS) reductase gene. The APS reductase-based MME strategy revealed intestinal SRB in the stomach and small intestine of 1-, 4-, and 7-day-old mice and throughout the gastrointestinal tract of 14-, 21-, 30-, 60-, and 90-day-old mice. Phylogenetic analysis of APS reductase amplicons obtained from the stomach, middle small intestine, and cecum of neonatal mice revealed that Desulfotomaculum spp. may be a predominant SRB group in the neonatal mouse intestine. Dot blot hybridizations with SRB-specific 16S ribosomal DNA (rDNA) probes demonstrated SRB colonization of the cecum and colon pre- and postweaning and colonization of the stomach and small intestine of mature mice only. The 16S rDNA hybridization data further demonstrated that SRB populations were most numerous in intestinal regions harboring sulfomucin-containing goblet cells, regardless of age. Reverse transcriptase PCR analysis demonstrated APS reductase mRNA expression in all intestinal segments of 30-day-old mice, including the stomach. These results demonstrate for the first time widespread colonization of the mouse intestine by dissimilatory SRB and evidence of spatial-specific SRB populations and sulfomucin patterns along the gastrointestinal tract.

Aging↗

[Ethanol and the gastrointestinal tract].

The effects of ethanol upon the gastrointestinal tract (mouth, pharynx, esophagus, stomach, duodenum, Oddi's sphincter, small bowel, colon and rectum) were reviewed. Several studies showed that the incidence of cancer in the mouth and pharynx is increased in alcoholics as a consequence of ethanol effects and probably those of other compounds found in liquors. The gastroesophageal reflux disease may be induced by alcohol since it reduces the pressure in the lower and the upper esophageal sphincter, as well as the extent of primary peristalsis. Several studies showed a strong correlation between esophageal cancer and alcohol abuse. The risk for developing this kind of tumour is significantly increased when alcohol abuse and smoking coexist. Alcoholism predisposes patients to Mallory-Weiss syndrome as well as to bleeding of esophageal varices Ethanol may affect gastric secretion, motility, and permeability. Some drugs acting upon the gastric alcohol-dehydrogenase are able to affect gastric absorption of ethanol. Eradication of Helicobacter pylori increases the activity of alcohol-dehydrogenase in the pyloric antrum. The effects of alcohol upon the gastric mucosa include caustic damage, retrograde diffusion of H+, and cytoprotection. This agent may cause an acute gastritis but it is probably not involved in chronic gastritis. Whether alcohol is a risk factor for ulcer or not is unknown. Some studies found an increased incidence of gastric cancer associated with consumption of beer, wine and vodka. Some authors reported a decreased pressure in Oddi's sphincter while others found it increased in association with the consumption of ethanol. The acute and the chronic consumption of alcohol may affect the structure of small bowel as well as the absorption of nutrients. Several studies reported a significant correlation between colorectal cancer and the chronic consumption of ethanol.

Alcoholism↗

Hepatic disease, the gastrointestinal tract, and rheumatic disease.

In previous years, this review concentrated on the relationship between pathology in the gastrointestinal tract and rheumatologic complaints associated with this pathology. This year, we have emphasized the relationship between hepatic disorders and rheumatologic complaints, although a resumé of recent literature pertaining to the gastrointestinal tract and its rheumatologic consequences is also presented. We believe it is necessary to divert our primary focus of attention because of recent developments in identifying the extrahepatic effects of hepatitis C infection and the current interest in abnormalities of drug metabolism in various rheumatic and autoimmune disorders. These recent developments bring us full circle in incriminating not only bacterial and dietary antigens in the pathogenesis of the spondyloarthropathies but also viruses and exogenous chemicals as potential etiologic agents in genetically predisposed hosts, resulting in the development of a variety of diseases, including glomerulonephritis, vasculitis, Sjögren's syndrome, and systemic lupus erythematosus.

Acute-Phase Proteins↗

A little known cell in the gastrointestinal tract.

A little known cell in the gastrointestinal tract has been described. The confusion over terminology is discussed. The question of the undifferentiated cell type is also considered. Although well recognised by gastroenterologists they remain little known in general. Their function is unknown. The various possibilities are summarized.

Animals↗

Surgical management of corrosive strictures following acid burns of upper gastrointestinal tract.

OBJECTIVE: Acid burns of the upper gastrointestinal tract produce a complex combination of lesions which can be grouped into five types, and existing surgical techniques have proved inadequate in treating some of these lesions. METHODS: Over the past 25 years 72 patients have needed operative treatment since they could not be managed by more conservative measures; the anatomical lesions in the five types and their surgical management are described. RESULTS: There were two early and one late death and morbidity was low in the long-term follow-up examinations, which included gastric secretory functions, transit time estimation with gamma camera and contrast radiography. CONCLUSIONS: The conclusions are 1) a variable approach is needed for each individual patient, 2) the right colon has proved suitable for esophageal bypass, 3) the ileum is included, when necessary, by making a side-to-side ileocaecoplasty to make it into a straight conduit and eliminate the caecal bulk and ileocaecal valve, 3) augmentation gastroduodenoplasty using a split jejunum or colon is very satisfactory for reconstructing a burnt contracted stomach, 4) posterior colopharyngeal anastomosis, performed as a pharyngoplasty by excising or widely incising the fibrosed posterior wall of the pharynx, restores normal deglutition, 5) parenteral vitamin B12 replacement is necessary in severe gastric burns.

Acids↗

Antibiotic susceptibility of potentially probiotic Bifidobacterium isolates from the human gastrointestinal tract.

Sixteen Bifidobacterium isolates from the human gastrointestinal tract were assayed for susceptibility to 44 antibiotics by soft agar overlay disc diffusion on TPY agar. Five isolates (3/7 B. bifidum and 2/3 B. breve) exhibited atypical antibiotic susceptibility profiles. Poor growth in the agar overlay accounted for susceptibility of B. bifidum but not B. breve isolates. All other isolates were resistant to cefoxitin (30 micrograms), aztreonam (30 micrograms), vancomycin (30 micrograms), amikacin (30 micrograms), gentamicin (10 micrograms), kanamycin (30 micrograms), streptomycin (10 micrograms), fusidic acid (10 micrograms), trimethoprim (5 micrograms), norfloxacin (10 micrograms), nalidixic acid (30 micrograms), metronidazole (5 micrograms), polymyxin B (300 micrograms) and colistin sulphate (10 micrograms), and they were susceptible to the six penicillins studied, cephalothin (30 micrograms), cefuroxime (30 micrograms), cefaclor (30 micrograms), ceftizoxime (30 micrograms), cefotaxime (30 micrograms), bacitracin (10 micrograms), chloramphenicol (30 micrograms), erythromycin (15 micrograms), clindamycin (2 micrograms), rifampicin (5 micrograms) and nitrofurantoin (300 micrograms). In addition, they varied in their susceptibility to cephradine (30 micrograms), cephazolin (30 micrograms), cefoperazone (75 micrograms), ceftriaxone (30 micrograms), ofloxacin (5 micrograms) and furazolidone (15 micrograms). They were resistant, or only marginally moderately susceptible, to ceftazidime (30 micrograms), netilmicin (10 micrograms), sulphamethoxazole (100 micrograms), cotrimoxazole (25 micrograms) and ciprofloxacin (5 micrograms), and susceptible or marginally moderately susceptible to tetracycline (30 micrograms). All B. bifidum isolates were susceptible to cefixime (5 micrograms). Four microorganism-drug combinations were evaluated for beta-lactamase activity but its absence suggested that cell wall impermeability was responsible for cephalosporin resistance among bifidobacteria. The antibiotic susceptibility of B. animalis 25527T was similar to that of the human isolates.

Anti-Bacterial Agents↗

[Intake of non-steroid preparation and risk of developing cancer of the upper gastrointestinal tract].

AIM: To compare occurrence of upper gastrointestinal tract (UGT) cancer in rheumatic patients taking long courses of nonsteroid antiinflammatory drugs (NSAD) and in non-rheumatic patients who have not received NSAD. MATERIAL AND METHODS: The study group of 1271 rheumatic patients on NSAD for at least 12 months. Control group of 654 patients free of rheumatic diseases and having no history of regular NSAD intake. The groups did not differ by the mean age, erosion and ulcer incidence. RESULTS: Esophagogastroduodenoscopy detected and histology confirmed adenocarcinoma in 2 patients of the study and 10 patients of the control group (0.16 and 1.5%, respectively, p < 0.001). CONCLUSION: Long-term treatment with NSAD lowers the risk of UGT tumors.

Adenocarcinoma↗

Saline lavage: a rapid, effective, and acceptable method for cleansing the gastrointestinal tract.

The standard preparation for cleansing the gastrointestinal tract for diagnostic studies such as barium enema usually involves dietary restrictions, purgatives, and cleansing enemas. This preparation is time consuming, often uncomfortable for the patient, and frequently unsuccessful. In this study, we examined the efficacy of saline lavage (without dietary restrictions or cleansing enemas) as a gentle, alternative method for cleansing the bowel, and compared lavage to the standard castor oil method of bowel preparation. Lavage cleansing was preferred by 75% of patients who had previously experienced a castor oil preparation. Although 11% of patients could not consume an adequate (4-liter) lavage volume, there was no significant difference in preparation success rate between the remaining lavage patients and the castor oil patients. Total preparation time for lavage (3 +/- 1 hr) was 60% less than for castor oil. The anticipated dehydration produced by castor oil and the hydration produced by lavage were confirmed. No significant changes were noted, however, in serum electrolytes with either method of preparation. Additional early studies are promising for the lavage method when used in inflammatory bowel disease patients and as a cleansing preparation for colonoscopy.

Barium Sulfate↗

Identification of cells expressing somatostatin receptor 2 in the gastrointestinal tract of Sstr2 knockout/lacZ knockin mice.

Somatostatin is found in neurons and endocrine cells in the gastrointestinal tract. The actions of somatostatin are mediated by a family of G-protein-coupled receptors that compose five subtypes (SSTR1-5), each of which is encoded by a separate gene. lacZ "knockin" mice, in which the reporter gene lacZ was engineered into the genomic locus of Sstr2 by gene targeting, were used to examine the expression pattern of Sstr2 and identify potential targets for neurally released and hormonal somatostatin in the gastrointestinal tract. In the body of the stomach, a large proportion of epithelial cells and subpopulations of myenteric neurons expressed Sstr2. Double- or triple-labeling with antisera to H(+)K(+)ATPase (to identify parietal cells) and/or histidine decarboxylase (to identify enterochromaffin-like [ECL] cells) combined with beta-galactosidase staining revealed that both parietal cells and ECL cells expressed Sstr2, and these two cell types accounted for almost all of the Sstr2-expressing epithelial cells. Somatostatin inhibits gastric acid secretion. The presence of SSTR2 on both parietal and ECL cells suggests that somatostatin acting on SSTR2 may reduce acid secretion by both acting directly on parietal cells and by reducing histamine release from ECL cells. In the small and large intestine, subpopulations of neurons in the myenteric and submucosal plexuses expressed Sstr2, and many of the Sstr2-expressing myenteric neurons also showed SSTR2(a) immunostaining. Most of Sstr2-expressing neurons in the myenteric plexus showed nitric oxide synthase (NOS) immunoreactivity. Previous studies have shown that NOS neurons are descending interneurons and anally projecting, inhibitory motor neurons. Thus, somatostatin acting at SSTR2 receptors on NOS neurons might modulate descending relaxation.

Animals↗

BRK/Sik expression in the gastrointestinal tract and in colon tumors.

Clones encoding the breast tumor kinase BRK were isolated from a normal human small intestinal cDNA library that was screened with the cDNA encoding the mouse epithelial-specific tyrosine kinase Sik. Although BRK and Sik share only 80% amino acid sequence identity, Southern blot hybridizations confirmed that the two proteins are orthologues. Sik was mapped to mouse distal chromosome 2, which shows conservation of synteny with human chromosome 20q13.3, the location of the BRK gene. BRK expression was examined in the normal gastrointestinal tract, colon tumor cell lines, and primary colon tumor samples. Like Sik, BRK is expressed in normal epithelial cells of the gastrointestinal tract that are undergoing terminal differentiation. BRK expression also increased during differentiation of the Caco-2 colon adenocarcinoma cell line. Modest increases in BRK expression were detected in primary colon tumors by RNase protection, in situ hybridization, and immunohistochemical assays. The BRK tyrosine kinase appears to play a role in signal transduction in the normal gastrointestinal tract, and its overexpression may be linked to the development of a variety of epithelial tumors.

Amino Acid Sequence↗

[Modulatory mechanisms involved in the parasympathetic excitatory neuro-effector transmission in the airway and gastrointestinal tracts--perspective for a new drug creation].

It is generally considered that dominant excitatory control of airway and gastrointestinal tract is exerted by the parasympathetic nervous system, and the transmitter output from the nerve terminals, mainly acetylcholine (ACh), is modulated in many ways for example by ACh itself, prostaglandins E series (PGE) neuropeptides and nitric oxide (NO). These modulations are probably due to the suppression of high-voltage-activated calcium channels in the nerve terminals, since, for example, ACh or prostaglandin E1 & E2 selectively suppressed both the N- and R-type Ca2+ currents, through M2 muscarinic and EP3-receptors, respectively in paratracheal ganglion cells. Parasympathetic nervous system also releases nonadrenergic-noncholinergic (NANC) inhibitory neurotransmitters in addition to ACh. The threshold level for ACh and NO release, for example, is almost identical, thereby suggesting the possible interactions between NO and ACh at the post-junctional cites, in addition to the prejunctional inhibitory action of NO to suppress ACh release from the nerve terminal. In this context, NO-donors, including SNAP or Cys-NO, reduced the amplitude of carbachol-induced Ca(2+)-dependent Cl- currents (I infinity h, I alpha(Ca)) dose-dependently (IC50: about 10 microM) in the cat tracheal myocytes, and similar inhibition was also exerted by dibutyryl cGMP (db-cGMP). However, two structurally distinct types of G-kinase inhibitor, H-8 (2.5 microM) and KT5823 (1 microM) failed to counteract the inhibitory effects of SNAP or db-cGMP. Another G-kinase-specific inhibitor, (Rp)-8-pCPT-cGMPS, itself caused a marked reduction in I infinity h, thereby indicating that inhibition of I infinity h by NO donors involves a cGMP-dependent but G-kinase-independent mechanism. All these experimental facts taken together indicate that there are pre- and post-junctional "brakings" in the excitatory parasympathetic neuro-effector transmission. Furthermore, in the gastrointestinal tract, Z-338, a newly synthetized gastroprokinetic agent, stimulates gastrointestinal motility through inhibition of the pre-junctional braking system through inhibition of M1 receptors. Such a drug may be useful to control the respiratory and gastrointestinal smooth muscles.

Animals↗

Dietary minerals in the gastrointestinal tract: hydroxypolymerisation of aluminium is regulated by luminal mucins.

The regulation of mineral absorption in the gastrointestinal tract is poorly understood. Recent work has identified an intracellular metal-ion transporter but considerable evidence suggests that both soluble and mucosally associated luminal metal-binding ligands regulate initial uptake. Molecules ranging from low molecular weight organic acids to large glycoproteins have been suggested but a definite role for any such species has remained elusive. Here, a series of analytical techniques, allowing for this wide variation in potential binding ligands, was applied to the study of intestinal contents and tissue of rats following different feeding protocols. Aluminium, that has a low endogenous background and maintains a high concentration in the gastrointestinal tract, was investigated as a suitable dietary metal with hydrolytic behaviour similar, for example, to copper, iron and zinc. High resolution nuclear magnetic resonance spectroscopy identified a number of endogenous low molecular weight weak ligands that are secreted into the intestinal lumen. These may slow the rate of hydroxy-polymerisation of hydrolytic metals, allowing their effective donation to less mobile, higher molecular weight binding ligands. Histochemical staining suggested that such species may be soluble mucins as these were consistently associated with luminal aluminium. Significantly, this interaction prevented hydroxy/phosphate precipitation of aluminium, even at supraphysiological levels of the element. This was confirmed with X-ray micro-analysis investigations of ex vivo luminal contents. Nevertheless, from phase distribution experiments, the majority (60-95%) of luminal aluminium was associated with the intestinal solid phase and further histochemistry confirmed this to be gelatinous mucus, chiefly as the mucosally adherent layer. All results suggest a major role for mucus in regulating the gastrointestinal absorption of aluminium. It is proposed that, initially, soluble luminal mucus prevents the hydroxy-precipitation of hydrolytic metals at intestinal pH, allowing their effective donation to the mucus layer. Based on the differing reported metal-mucus interactions, elements that bind well to mucus (Al3+, Fe3+), with kinetically slow rates of ligand exchange (Al3+ < Fe3+) will be less well absorbed than poorly bound elements with kinetically faster rates of ligand exchange (Cu2+, Zn2+ etc.). This mechanism would readily explain many of the reported observations on mineral availability, including the marked variation in absorption of different elements, the differential effects of dietary ligands on mineral uptake and the competition for absorption between different metals.

Aluminum↗

Microsatellite instability in adenocarcinomas of the upper gastrointestinal tract. Relation to clinicopathological data and family history.

We analyzed 66 adenocarcinomas arising in the upper gastrointestinal tract for microsatellite instability at eight microsatellite loci to investigate the role of these genetic alterations in the etiology of these tumors. We identified alterations in at least one locus in 11/46 adenocarcinomas of the stomach, in 2/15 adenocarcinomas arising in Barrett's esophagus, and in 1/5 adenocarcinomas of the duodenum and jejunum. Microsatellite instability in gastric tumors was found in 5/22 of intestinal, 1/3 of mixed, and 5/21 of diffuse type tumors. No relationship to the tumor stage (TNM), age, and survival time of the patients was observed. One patient had two synchronous gastric tumors both exhibiting microsatellite instability at multiple loci. His family history revealed four individuals in the maternal line afflicted with gastric carcinoma in three generations. Our data show that microsatellite instability is a genetic event in 11 to 24% of tumors of the upper gastrointestinal tract. The observation of microsatellite instability and a familial clustering of gastric tumors may suggest a genetic predisposition for a subset of gastric tumors, which may be identified by microsatellite analysis.

Adenocarcinoma↗

Vasopressin therapy for upper gastrointestinal tract hemorrhage. Has its efficacy been proven?

Of four reported studies of vasopressin therapy in acute upper gastrointestinal tract hemorrhage, three found vasopressin to be effective and one did not. The studies differed with regard to population, design, and methods. The one study that found vasopressin to be ineffective in controlling gastrointestinal tract hemorrhage may have been better controlled with regard to duration of therapy and evaluation of patients. However, the population studied appeared to be different and the authors may have failed to demonstrate a beneficial effect of vasopressin in a select subgroup of patients. Vasopressin dosing has also been a point of controversy. Hemodynamic data thus far support the use of low-dose infusions. The use of terlipressin (Glypressin), a new analogue of vasopressin, also appears promising.

Animals↗

Systematic assessment of massive bleeding of the lower part of the gastrointestinal tract.

A study of 83 patients admitted with massive bleeding in the lower part of the gastrointestinal tract is presented using a diagnostic approach primarily of angiography and colonoscopy with the adjunctive investigations of scintigraphy, small intestine series and computed tomographic scan. The source of bleeding was identified preoperatively in 74 patients. Nine patients had a diagnostic laparotomy and the cause was found in an additional seven. A source was not identified in two patients at exploration and a blind resection was not performed. The two patients have not had recurrent bleeding four and nine years postlaparotomy. The sites of bleeding were colon in 44 patients, small intestine in 24 and the anorectum in 11. Sixty-five patients were treated operatively, two by angiographic embolization and two by endoscopic electrocoagulation. Fourteen patients were managed conservatively. The mortality rate was 10.8 percent and five patients rebled after treatment. We conclude that a thorough systematic assessment of patients with bleeding in the lower part of the gastrointestinal tract is important to localize the site of the hemorrhage. Exploratory laparotomy is the final diagnostic modality, and if a source has not been identified, a blind colonic resection should not be performed.

Adult↗

c-Kit immunoreactive interstitial cells in the human gastrointestinal tract.

c-Kit immunopositive cells are considered to be pacemakers and/or mediators of neurotransmission in the gastrointestinal tract. They also correspond to the interstitial cells of Cajal (ICs) in mice. The normal distribution of c-Kit positive cells and their relation to ICs in the human gastrointestinal tract remain unclear. In this study we examine the distribution of c-Kit positive cells and their ultrastructure in normal human tissue. We then classified them and examined their relationship to ICs. Thirty nine samples of gut from the esophagus to the sigmoid colon from humans (ranging in age from a 16 week old fetus to a 57 year old and without motility disorders), were processed for immunohistochemistry, electronmicroscopy and immuno-electronmicroscopy. c-Kit immunopositive cells were located in the external muscle from the lower esophagus to the sigmoid colon, wherever the external muscle was composed of smooth muscle cells, and they were classified morphologically into two groups. Cells in the first group were mainly spindle-shaped bipolar cells with few branches; these cells ran parallel to nearby smooth muscle. Ultrastructurally, they possessed many intermediate filaments and caveolae. The spindle-shaped cells were present in the esophagus, stomach and small intestine. The second group of cells were located only in the colon, and were multipolar or bipolar cells with numerous branches. Cells in the second group were also rich in caveolae and/or smooth endoplasmic reticulum, but intermediate filaments were not prominent. Although both groups of c-Kit immunopositive cells corresponded to ICs, some ICs in the human gut do not appear to express c-Kit immunoreactivity.

Adolescent↗

Comparison of the intravenous and intraperitoneal routes of administration of tritiated thymidine in studies of cell production in the gastrointestinal tract of the rat.

Incorporation of 3H-Thymidine into DNA-synthesizing cells of the gastrointestinal tract of the rat was examined following administration of the isotope by intraperitoneal and intravenous routes. Estimates of whole tissue incorporation expressed as DPM/mg dry weight and of proliferating cells expressed as DPM/crypt or gland in the different segments of the gut indicated no differences in the degree of 3H-TdR uptake into DNA following intraperitoneal or intravenous routes of administration. The possibility of misdirected I.P. injections was examined following injection of 3H-TdR into the cecum or bladder. DPM/mg wet weight of gastrointestinal tissues indicated reduction in the uptake of 3H-TdR into DNA of intestinal tissues following intracecal and intrabladder administration of 3H-Tdr. The intraperitoneal route of administration of 3H-TdR appears to be equally effective in the distribution of the isotope into different segments of the gut when compared to the intravenous route and is a more convenient method in studies of cell production in the gastrointestinal tract of the rat.

Animals↗