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PubMed2001

Vagal-enteric interface: vagal activation-induced expression of c-Fos and p-CREB in neurons of the upper gastrointestinal tract and pancreas.

Many gastrointestinal and pancreatic functions are under strong modulatory control by the brain via the vagus nerve. To start identifying location and neurochemical phenotype of the enteric neurons receiving functional vagal efferent input, we activated vagal preganglionic neurons either by electrical or chemical stimulation and examined the expression of phosphorylated CREB (c-AMP response element binding protein) and the immediate early gene c-Fos. There was no spontaneous expression of both markers in the pancreas and considerable spontaneous expression of p-CREB but not Fos in the upper GI-tract. Unilateral electrical vagal stimulation-induced p-CREB was found in 40% of neurons in the head of the pancreas. Fos expression was found in 70-90% of neurons in the esophagus and stomach, in 20-30% of myenteric plexus neurons and 5-15% in submucosal neurons of the proximal duodenum. Double-labeling experiments showed that a majority of pancreatic neurons and about 25-35% of neurons in the stomach and duodenum contain NADPH-diaphorase and that many of these receive functional vagal input. Other neurons that can be vagally activated contain gastrin-releasing peptide or calretinin. Chemical stimulation of the dorsal surface of the caudal brainstem with the stable TRH analog RX77368 resulted in selective activation of vagal efferents with expression of Fos in a small number of gastric myenteric plexus neurons. The results demonstrate the suitability of this method to investigate magnitude and local distribution of vagal input to the enteric nervous system as well as specificity of its neurochemically coded pathways. They represent the first step in the identification of function-specific units of parasympathetic vagal outflow.

Activating Transcription Factor 1↗
PubMed2005

Radiation therapy and upper gastrointestinal tract: esophageal, gastric, and pancreatic cancer. Toward new standards?

PURPOSE OF REVIEW: To emphasize the role and place of chemoradiation in the treatment of patients with upper gastrointestinal tract cancer. RECENT FINDINGS: For esophagus cancer, in resectable stages IIA to IIB, squamous cell types, surgery remains standard treatment, and preoperative chemoradiation is investigational. After the results of two randomized trials conducted in France and Germany, however, chemoradiation alone is challenging surgery. In adenocarcinomas, preoperative chemoradiation is under investigation. In both types, new studies incorporating targeted therapies to chemoradiation are starting. For gastric cancer, chemoradiation after operation is standard of care in the United States but is still discussed in Europe. Preoperative chemoradiation is in current development, and future trials will compare preoperative strategies and strategies after operation. For pancreatic cancer, after a curative resection, chemoradiation in the United States and chemotherapy in Europe are standard of care, respectively. An ongoing European trial is comparing these two strategies after operation. SUMMARY: Recommendations are issued from the analysis of recently published clinical trials. New areas of development are discussed.

Esophageal Neoplasms↗
PubMedDate not supplied

Bacteria and the gastrointestinal tract: beneficial and harmful effects.

Bacteria are unique microorganisms that have a variety of physiological functions which are beneficial to human beings. However, bacteria can also be harmful and cause infections if translocated from the gastrointestinal tract to the epithelial tissue following surgery. The process of translocation can lead to surgical wounds becoming contaminated with gastrointestinal microbes such as Escherichia coli, Proteus or Klebsiella species. Bacteria can also cause severe gastrointestinal infections as a consequence of the ingestion of contaminated food. Food-borne bacterial infections can lead to serious consequences for the patient. Nurses managing the care of surgical patients and older people need to be aware of the physiological role that bacteria play but also the detrimental effects of bacterial translocation or ingestion particularly in older people, infants and people who are immunosuppressed.

Bacteria↗
PubMedDate not supplied

Effects of polyvalency of glycotopes and natural modifications of human blood group ABH/Lewis sugars at the Galbeta1-terminated core saccharides on the binding of domain-I of recombinant tandem-repeat-type galectin-4 from rat gastrointestinal tract (G4-N).

In our recent publication, we defined core aspects of the carbohydrate specificity of domain-I of recombinant tandem-repeat-type galectin-4 from rat gastrointestinal tract (G4-N), especially its potent interaction with the linear tetrasaccharide Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc (Ibeta1-3L). The assumed role of galectin-4 as a microvillar raft stabilizer/organizer and as a malignancy-associated factor in hepatocellular and gastrointestinal carcinomas called for further refinement of its binding specificity. Thus, the effects of polyvalency of glycotopes and natural modifications of human blood group ABH/Lewis sugars at the terminal Galbeta1-core saccharides were thoroughly examined by the enzyme-linked lectinosorbent and lectin-glycan inhibition assays. The results indicate that (a) a high-density of polyvalent Galbeta1-3/4GlcNAc (I/II), Galbeta1-3GalNAc (T) and/or GalNAcalpha1-Ser/Thr (Tn) strongly favors G4-N/glycoform binding. These glycans were up to 2.3 x 10(6), 1.4 x 10(6), 8.8 x 10(5), and 1.4 x 10(5) more active than Gal, GalNAc, monomeric I/II and T, respectively; (b) while lFuc is a poor inhibitor, its presence as alpha1-2 linked to terminal Galbeta1-containing oligosaccharides, such as H active Ibeta1-3L, markedly enhances the reactivities of these ligands; (c) when blood group A (GalNAcalpha1-) or B (Galalpha1-) determinants are attached to terminal Galbeta1-3/4GlcNAc (or Glc) oligosaccharides, the reactivities are also increased; (d) with lFucalpha1-3/4 linked to sub-terminal GlcNAc, the reactivities of these haptens are reduced; and (e) short chain Le(a)/Le(x)/Le(y) and the short chains of sialyl Le(a)/Le(x) are poor inhibitors. These distinct binding features of G4-N establish the important concept of affinity enhancement by high density polyvalencies of glycotopes (vs. multi-antennary I/II) and by introduction of an ABH key sugar to Galbeta1-terminated core glycotopes. The polyvalent ligand binding properties of G4-N may help our understanding of its crucial role for cell membrane raft stability and provide salient information for the optimal design of blocking substances such as anti-tumoral glycodendrimers.

ABO Blood-Group System↗
PubMed2005

Novel microbial diversity adherent to plant biomass in the herbivore gastrointestinal tract, as revealed by ribosomal intergenic spacer analysis and rrs gene sequencing.

It is well recognized that a dynamic biofilm develops upon plant biomass in the herbivore gastrointestinal tract, but this component of the microbiome has not previously been specifically sampled, or directly compared with the biodiversity present in the planktonic fraction of digesta. In this study, the digesta collected from four sheep fed two different diets was separated into three fractions: the planktonic phase, and the microbial populations either weakly or tightly adherent to plant biomass. The community DNA prepared from each fraction was then subjected to both ribosomal intergenic spacer analysis (RISA) and denaturing gradient gel electrophoresis (DGGE). Both types of analysis showed that dietary factors influence community structure, and that the adherent fractions produced more complex profiles. The RIS-clone libraries prepared from the planktonic and adherent populations were then subjected to restriction fragment length polymorphism (RFLP) and DNA sequence analyses, which resulted in a far greater degree of discrimination among the fractions. Although many of the sequenced clones from the adherent populations were assigned to various clusters within the low G+C Gram-positive bacteria, the clone libraries from animals consuming an all-grass diet were largely comprised of novel lineages of Clostridium, while in animals consuming the starch-containing diet, Selenomonas and Ruminococcus spp. were the dominant low G+C Gram-positive bacteria. Additionally, the libraries from hay-fed animals also contained clones most similar to asaccharolytic Clostridia, and other Gram-positive bacteria that specialize in the transformation of plant phenolic compounds and the formation of cinnamic, phenylacetic and phenylpropionic acids. These results reveal, for the first time, the phylogeny of adherent subpopulations that specialize in the transformation of plant lignins and other secondary compounds, which potentiate polysaccharide hydrolysis by other members of the biofilm.

Animals↗
PubMed1988

Effect of oral iron therapy on the upper gastrointestinal tract. A prospective evaluation.

This study assesses the effect of oral iron therapy on the upper gastrointestinal tract and fecal occult blood testing. Fourteen healthy volunteers completed a checklist of gastrointestinal symptoms, underwent endoscopy and biopsy of the stomach and duodenum, and supplied a fresh stool sample for Hemoccult and HemoQuant testing. They then took ferrous sulfate 325 mg per os tid for two weeks and had the same evaluation repeated. Gastrointestinal symptoms were rated by the patients on a scale of 0-3, endoscopic findings were numerically scored (0-4), and the biopsies were graded blindly. Thirteen other healthy volunteers took ferrous sulfate 325 mg per os tid for one week and had Hemoccult testing of stool at days 0 and 7. All subjects developed dark stools, and significant nausea and diarrhea were noted (0.1 +/- 0.1 to 0.9 +/- 0.3, P less than 0.05 for both symptoms). Only 1/27 had a questionably trace-positive Hemoccult test (two observers disagreed) and no significant difference was seen in HemoQuant testing (1.4 +/- 0.5 to 1.8 +/- 0.7 mg Hb/g). A significant increase was seen in endoscopic abnormalities in the stomach (0.1 +/- 0.1 to 1.5 +/- 0.3, P = 0.003), consisting of erythema, small areas of subepithelial hemorrhage, and, in two subjects, erosions. Biopsies showed no significant change after iron therapy. We conclude that (1) oral ferrous sulfate rarely causes Hemoccult-positive stools, and patients with positive Hemoccult tests on iron therapy require further evaluation; and (2) oral iron may cause mild endoscopic abnormalities in the stomach which are of uncertain clinical significance.

Administration, Oral↗
PubMed2001

E2 and not P4 increases NO release from NANC nerves of the gastrointestinal tract: implications in pregnancy.

In women, during pregnancy, there is decreased motility of the gastrointestinal tract leading to a delay in gastric emptying and an increase in colonic transit time. Whether the rise in estradiol (E2) or progesterone (P4) is responsible for this effect is controversial. As the nitrergic component of the nonadrenergic, noncholinergic (NANC) nerves is responsible for modulating gastrointestinal motility in vivo, the purpose of this study was to evaluate whether the increased release of nitric oxide (NO) from the nitrergic component of the NANC nerves innervating the gastric fundus and colon that occurs during late pregnancy in rats is mediated by E2 or P4. Ovariectomized rats treated with E2 or P4 alone or in combination were used for our studies. We also wanted to assess the cellular and molecular mechanisms involved. The NANC activity was studied by assessing changes in tone after application of electric field stimulation (EFS). The role of NO was determined by observing the effects of EFS in the presence and absence of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the reversibility of the effects of L-NAME by L-arginine. Our studies indicated that there was increased magnitude of relaxation of isolated strips of rat gastric fundus and rat colon after application of EFS to tissues obtained from animals treated with E2 alone or a combination of E2 + P4 but not from those treated with P4 alone. L-NAME attenuated relaxation responses in E2- and E2 + P4-treated animals. To elucidate whether the increased NO release may be due to an increase in neuronal NOS (nNOS) protein, we used both Western blot analysis and immunohistochemistry. We also used RT-PCR to determine whether there was an increase in nNOS mRNA after treatment with sex steroids. In nonpregnant animals, nNOS was detected by Western blot in the fundus and the colon and was barely detectable in the ileum. In pregnancy, there was an increase in nNOS in both the gastric fundus and the colon. The nNOS protein was also increased in ovariectomized animals treated with either E2 alone or E2 + P4 but not P4 alone when compared with ovariectomized animals receiving vehicle. Our results indicated that there was an increase in nNOS protein that was localized to the neurons of the myenteric plexus in the gastric fundus and colon in E2- and E2 + P4-treated animals, but this increase was not observed in animals treated with P4 alone. This increase in nNOS protein was accompanied by an increase in nNOS mRNA. These results suggest the possibility that E2, rather than P4, may be responsible for the delay in gastric emptying and increase in colonic transit time observed in pregnancy.

Animals↗
PubMedDate not supplied

Comparative ultrasonographic investigations of the gastrointestinal tract and the liver in healthy and diseased pigeons.

The use of ultrasound as a diagnostic tool in birds has been documented for cardiac, urogenital, and liver disease. However, its use in gastrointestinal tract disease is not defined. Therefore, the purpose of this study was to compare the ultrasonographic findings of the intestine and liver of six healthy racing pigeons with those of six racing pigeons with gastrointestinal disease. The echogenicity of the liver was significantly different between the two groups. Pigeons with gastrointestinal disease had less homogeneous liver echogenicity with focal heterogeneous areas and the hepatic blood vessels were visible and dilated. The duodenum was visualized and its mean diameter of 7.2 +/- 0.3 mm in the diseased pigeons was significantly wider (P < or = 0.001) than the 5.7 +/- 0.2 mm in healthy birds. The thickness of the duodenal wall in healthy and diseased pigeons was 1.6 +/- 0.1 and 2.4 +/- 0.1 mm, respectively, and they were significantly different (P < or = 0.001). We defined baseline measurements for the duodenal loop in pigeons and provided evidence that ultrasound can be a useful diagnostic tool for investigating intestinal disease in pigeons.

Animals↗
PubMed2004

Liquid chromatography-mass spectrometry analysis of hydroxylated polycyclic aromatic hydrocarbons, formed in a simulator of the human gastrointestinal tract.

Described is a liquid chromatography-mass spectrometry (LC-MS) procedure for the determination of hydroxylated biotransformation products of polycyclic aromatic hydrocarbons (PAH) in the human gastrointestinal tract. The formation of hydroxylated PAHs was monitored upon incubation of PAHs with colon microbiota from the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The analytical method consisted of a biomass removal step followed by a solid phase extraction (SPE) step using C18 packed columns to remove non-digested food compounds and microbial metabolites that interfere with the detection of the target compounds. For quantification, 9-hydroxyphenanthrene (13)C(6)was used as the internal standard. The detection limits of the hydroxylated PAHs were generally in the range 0.36-14.09 microg x l(-1), based on a signal/noise ratio of 3:1. The recovery of hydroxylated PAHs in intestinal suspension was variable ranging from 45 to 107%, with relative standard deviation (R.S.D.) between 5 and 17%. The analytical procedure was used to show the microbial production of 1-hydroxypyrene and 7-hydroxybenzo(a)pyrene, metabolites that may give colon incubated PAHs bioactive properties.

Calibration↗
PubMed2004

Acid resistance systems required for survival of Escherichia coli O157:H7 in the bovine gastrointestinal tract and in apple cider are different.

Escherichia coli O157:H7 is a highly acid-resistant food-borne pathogen that survives in the bovine and human gastrointestinal tracts and in acidic foods such as apple cider. This property is thought to contribute to the low infectious dose of the organism. Three acid resistance (AR) systems are expressed in stationary-phase cells. AR system 1 is sigma(S) dependent, while AR systems 2 and 3 are glutamate and arginine dependent, respectively. In this study, we sought to determine which AR systems are important for survival in acidic foods and which are required for survival in the bovine intestinal tract. Wild-type and mutant E. coli O157:H7 strains deficient in AR system 1, 2, or 3 were challenged with apple cider and inoculated into calves. Wild-type cells, adapted at pH 5.5 in the absence of glucose (AR system 1 induced), survived well in apple cider. Conversely, the mutant deficient in AR system 1, shown previously to survive poorly in calves, was susceptible to apple cider (pH 3.5), and this sensitivity was shown to be caused by low pH. Interestingly, the AR system 2-deficient mutant survived in apple cider at high levels, but its shedding from calves was significantly decreased compared to that of wild-type cells. AR system 3-deficient cells survived well in both apple cider and calves. Taken together, these results indicate that E. coli O157:H7 utilizes different acid resistance systems based on the type of acidic environment encountered.

Animals↗
PubMed2005

Cytoplasmic, but not nuclear, expression of the neuronal nuclei (NeuN) antibody is an exclusive feature of Dogiel type II neurons in the guinea-pig gastrointestinal tract.

This study aimed to reveal if NeuN, a neuronal nuclei (NeuN) antibody, is a selective marker of intrinsic primary afferent neurons (IPANs) in the guinea-pig gastrointestinal tract as previously hypothesised. The NeuN immunoreactivity was found in the enteric nervous system with exception of the esophagus. Two groups of NeuN-expressing neurons were observed: neurons with immunostained nuclei and cytoplasm (NeuN(NC)) and neurons only expressing immunoreactivity in their nuclei (NeuN(N)). The NeuN(N)-immunoreactive neurons were found in the myenteric plexus of the stomach and the colon. In the stomach, none of the NeuN(N)-expressing neurons, of which 55+/-3% co-expressed calbindin, had a Dogiel type I or II morphology. The NeuN(N)-positive neurons of the colon, which did not express calbindin, did not resemble a Dogiel type II morphology either, but were small-sized neurons. The NeuN(NC)-immunoreactive neurons were observed in both the small and large intestine. These neurons were smooth-contoured and bigger-sized, resembling a Dogiel type II morphology. Some of these neurons co-expressed calbindin. The present data reveal the existence of two populations of Dogiel type II neurons, exhibiting NeuN(NC)+/calbindin+ or NeuN(NC)+/calbindin- immunoreactivity, in the intestine. Assuming that all IPANs exhibit a Dogiel type II morphology, we conclude that the cytoplasmic expression of NeuN is an exclusive feature of IPANs.

Animals↗
PubMed1996

A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract.

Electrical rhythmicity in gastrointestinal muscles has been studied for a century, but the pacemakers driving this phenomenon have been elusive. Anatomic studies suggest that interstitial cells of Cajal (ICC) may be pacemakers and conductors of electrical activity. ICC may also mediate neurotransmission from enteric neurons. Functional evaluations of ICC include the following. (1) Electrophysiology experiments on dissected muscle strips show that slow waves originate from specific sites. These pacemaker areas are populated by networks of ICC that make gap junctions with smooth muscle cells. Removal of pacemaker regions interferes with slow wave generation and propagation. (2) Chemicals that label ICC histochemically can damage ICC and abolish rhythmicity. (3) isolated ICC are spontaneously active, and several voltage-dependent ion channels, including a low-threshold Ca2+ conductance, are expressed. (4) ICC are innervated by enteric neurons, and they respond to neurotransmitters. ICC may produce nitric oxide and amplify inhibitory neurotransmission. (5) Some classes of ICC fall to develop in animals with mutations in c-kit or stem cell factor, the ligand for c-Kit receptors. Without ICC, electrical slow waves are absent. Many questions remain about the function of ICC, but modern technologies should now facilitate rapid progress toward determining the role of these cells in normal physiology and pathological conditions.

Animals↗
PubMed1992

Gastrointestinal symptoms in patients infected with human immunodeficiency virus: relevance of infective agents isolated from gastrointestinal tract.

The correlation of gastrointestinal symptoms and infections in 186 consecutive patients with human immunodeficiency virus (HIV) infection undergoing diagnostic endoscopy (oesophagogastroduodenoscopy, n = 124; colonoscopy, n = 37; both, n = 25) was investigated. Biopsy and stool samples were examined for infective agents. Only weight loss (p = 0.003) and dysphagia (p = 0.027) were more common in patients at stage CDC IV compared with earlier stages. In three of 27 patients at stage II/III and in 93 of 159 patients at stage IV an infective agent was identified in stool or gastrointestinal biopsy specimen (p < 0.001). Cytomegalovirus (n = 35), Candida sp (n = 28), M avium complex (n = 10), and Cryptosporidium (eight) were the most frequent agents detected. At stage IV, diarrhoea was more frequent in infected compared with non-infected patients (p = 0.006); however, an infective agent was also found in 39 of 82 patients at stage IV without diarrhoea. The frequency of gastrointestinal symptoms was not consistently increased in patients harbouring specific infective agents compared with non-infected patients. Our findings indicate that the pathogenic relevance of a gastrointestinal infection in HIV infected patients has to be verified and indirectly support the existence of an HIV associated enteropathy.

Adult↗
PubMed1992

Mitochondrial gene expression in the human gastrointestinal tract.

In the human gastrointestinal epithelium, in situ hybridisation demonstrates that 12 S and 16 S mitochondrial ribosomal RNAs show maximal steady-state levels on the surface epithelial cells of the normal small intestine and colon. The mitochondrial mRNAs, cytochrome b and NADH dehydrogenase (IV) have a uniform distribution throughout the crypt and surface (villus) epithelial cells of the small intestine and colon. Histochemical stains for the activity of the mitochondrial respiratory chain enzymes succinate dehydrogenase and cytochrome oxidase also show almost uniform activities throughout the crypt-surface epithelial cell axis in the small and large intestines. In sections of normal human oesophagus the levels of mitochondrial ribosomal RNAs, mitochondrial mRNAs and the activities of mitochondrial respiratory chain enzymes are maximal over the basal cells of the stratified squamous epithelium. These results show a relative increase in mitochondrial ribosomal RNA expression compared with mitochondrial mRNAs in surface cells of simple intestinal epithelia.

DNA Probes↗