Smoothelin is a specific and robust marker for distinction of muscularis propria and muscularis mucosae in the gastrointestinal tract

As tumour specimens and biopsy specimens become smaller, recognition of anatomical structures relevant for staging is increasingly challenging. So far no marker is known that reliably discriminates between muscularis propria (MP) and muscularis mucosae (MM) of the gastrointestinal tract. Recently, smoothelin expression has been shown to differ in MP and MM of the urinary bladder. We aimed to analyse the expression of smoothelin in the gastrointestinal tract in MP and MM in order to define a novel diagnostic tool to identify MM bundles.

Multimodal therapy of functional gastrointestinal disorders

A multimodal approach is state-of-the art for effective treatment of functional gastrointestinal disorders (FGD) like irritable bowel syndrome and functional dyspepsia. Based on the now established view that the pathogenesis of FGD is multicausal, evidence-based therapeutic options comprise education about the nature of the disorder, dietary modifications, relaxation techniques, behavioral changes, and pharmacological treatments. These therapies are variously combined depending on the severity of the FGD and the individual needs of the patient. Our overview portrays the options for the therapy of FGD and proposes that these are best provided by an interdisciplinary team of primary care physicians, gastroenterologists, and psychosomatic medicine specialists.

[Pathogenesis of functional gastrointestinal disorders - an interdisciplinary perspective]

Functional gastrointestinal disorders (FGD) are highly prevalent worldwide. Recent research demonstrates that complex and interacting biological and behavioral mechanisms contribute particularly to the pathogenesis of irritable bowel syndrome and functional dyspepsia. Dysregulation of the enteral, neuroenteric, visceral-autonomic, and central nervous systems are important biological contributors, whereas the psychological state of a patient may evidently modulate aspects related to biological stress reactivity and somatic perception both playing a role in the clinical manifestation of FGD. Our overview clearly shows that an interdisciplinary perspective of the pathogenesis of FGD may best serve clinicians and patients.

Expression and function of 5-hydroxytryptamine 4 receptors in smooth muscle preparations from the duodenum, ileum, and pelvic flexure of horses without gastrointestinal tract disease

OBJECTIVE: To evaluate the expression of the 5-hydroxytryptamine 4 (5-HT4) receptor subtype and investigate the modulating function of those receptors on contractility in intestinal tissues obtained from horses without gastrointestinal tract disease. SAMPLE POPULATION: Smooth muscle preparations from the duodenum, ileum, and pelvic flexure collected immediately after slaughter of 24 horses with no history or signs of gastrointestinal tract disease. PROCEDURES: In isometric organ baths, the contractile activities of smooth muscle preparations in response to 5-hydroxytryptamine and electric field stimulation were assessed; the effect of tegaserod alone or in combination with 5-hydroxytryptamine on contractility of intestinal specimens was also investigated. Presence and distribution of 5-HT4 receptors in intestinal tissues and localization on interstitial cells of Cajal were examined by use of an immunofluorescence technique. RESULTS: Widespread 5-HT4 receptor immunoreactivity was observed in all intestinal smooth muscle layers; 5-HT4 receptors were absent from the myenteric plexus and interstitial cells of Cajal. In electrical field-stimulated tissue preparations of duodenum and pelvic flexure, tegaserod increased the amplitude of smooth muscle contractions in a concentration-dependent manner. Preincubation with tegaserod significantly decreased the basal tone of the 5-HT-evoked contractility in small intestine specimens, compared with the effect of 5-HT alone, thereby confirming that tegaserod was acting as a partial agonist. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, 5-HT4 receptors on smooth muscle cells appear to be involved in the contractile response of the intestinal tract to 5-hydroxytryptamine. Results suggest that tegaserod may be useful for treatment of reduced gastrointestinal tract motility in horses.

Susceptibility of Aethina tumida (Coleoptera: Nitidulidae) Larvae and Pupae to Entomopathogenic Nematodes

In this study, we evaluated the potential use of entomopathogenic nematodes as a control for the beetle Aethina tumida Murray (Coleoptera: Nitidulidae). In particular, we conducted 1) four screening bioassays to determine nematode (seven species, 10 total strains tested) and application level effects on A. tumida larvae and pupae, 2) a generational persistence bioassay to determine whether single inoculations with nematodes would control multiple generations of A. tumida larvae in treated soil, and 3) a field bioassay to determine whether the nematodes would remain efficacious in the field. In the screening bioassays, nematode efficacy varied significantly by tested nematode and the infective juvenile (IJ) level at which they were applied. Although nematode virulence was moderate in screening bioassays 1-3 (0 - 68% A. tumida mortality), A. tumida mortality approached higher levels in screening bioassay 4 (nearly 100% after 39 d) that suggest suitable applicability of some of the test nematodes as field controls for A. tumida. In the generational persistence bioassay, Steinernema Hobrave Cabanillas, Poinar & Raulston 7-12 strain and Heterorhabditis indica Poinar, Karunaka & David provided adequate A. tumida control for 19 wk after a single soil inoculation (76-94% mortality in A. tumida pupae). In the field bioassay, the same two nematode species also showed high virulence toward pupating A. tumida (88-100%) mortality. Our data suggest that nematode use may be an integral component of an integrated pest management scheme aimed at reducing A. tumida populations in bee colonies to tolerable levels.

Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems

Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options.

Resistance against strongylid nematodes in two high prevalence Equine Recurrent Airway Obstruction families has a genetic basis

A recent study showed increased resistance against strongylid nematodes in offspring of a stallion affected by recurrent airway obstruction (RAG) compared with unrelated pasture mates. Resistance against strongylid nematodes was associated with RAG affection. Hypothesis: Resistance against strongylid nematodes has a genetic basis. The genetic variants influencing strongylid resistance also influence RAG susceptibility. Faecal samples from the half-sibling offspring of two RAG-affected Warmblood stallions 98 offspring from the first family (family 1) and 79 from the second family (family 2) were analysed using a combined sedimentation-flotation method. The phenotype was defined as a binary trait - either positive or negative for egg shedding. The influence of non-genetic factors on egg shedding was analysed using SAS, the mode of inheritance was investigated using PAP and iBay, and the association between shedding of strongyle eggs and RAG was estimated by odds ratios. Previously established genotypes for 315 microsatellite markers were used for QTL analyses using GRID QTL. The inheritance of "strongylid egg shedding" is influenced by major genes on ECA15 and ECA20. Shedding of strongylid eggs is associated with RAG in family 1 but not in family 2. Conclusions: The status of "shedding of strongyle eggs" has a genetic background. The results were inconclusive as to whether "egg shedding" and RAG share common genetic components. Our results suggest that it may be possible to select for resistance against strongylid nematodes.

Gastrointestinal tract mucosal histomorphometry and epithelial cell proliferation and apoptosis in neonatal and adult dogs

In this study, the hypothesis was tested that the size of gastrointestinal tract (GIT) mucosal components and rates of epithelial cell proliferation and apoptosis change with increasing age. The aims were to quantitatively examine GIT histomorphology and to determine mucosal epithelial cell proliferation and apoptosis rates in neonatal (<48 h old) and adult (8 to 11.5 yr old) dogs. Morphometrical analyses were performed by light microscopy with a video-based, computer-linked system. Cell proliferation and apoptosis of the GIT epithelium were evaluated by counting the number of Ki-67 and caspase-3-positive cells, respectively, using immunohistochemical methods. Thickness of mucosal, glandular, subglandular, submucosal and muscular layers, crypt depths, villus heights, and villus widths were consistently greater (P < 0.05 to P < 0.001), whereas villus height/crypt depth ratios were smaller (P < 0.001) in adult than in neonatal dogs. The number of Ki-67-positive cells in stomach, small intestine, and colon crypts, but not in villi, was consistently greater (P < 0.01) in neonatal than in adult dogs. In contrast, the number of caspase-3-positive cells in crypts of the stomach, small intestine, and colon and in villi was not significantly influenced by age. In conclusion, canine GIT mucosal morphology and epithelial cell proliferation rates, but not apoptosis rates, change markedly from birth until adulthood is reached.

GLP-2 receptors in human disease: high expression in gastrointestinal stromal tumors and Crohn's disease

Peptide hormones of the glucagon-like peptide (GLP) family play an increasing clinical role, as reported for GLP-1 in diabetes therapy and insulinoma diagnostics. GLP-2, despite its known trophic and anti-inflammatory intestinal actions translated into preliminary clinical studies using the GLP-2 analogue teduglutide for treatment of short bowel syndrome and Crohn's disease, remains poorly characterized in terms of expression of its receptor in tissues of interest. Therefore, the GLP-2 receptor expression was assessed in 237 tumor and 148 non-neoplastic tissue samples with in vitro receptor autoradiography. A GLP-2 receptor expression was present in 68% of gastrointestinal stromal tumors (GIST). Furthermore, GLP-2 receptors were identified in the intestinal myenteric plexus, with significant up-regulation in active Crohn's disease. The GLP-2 receptors in GIST may be used for clinical applications like in vivo targeting with radiolabelled GLP-2 analogues for imaging and therapy. Moreover, the over-expressed GLP-2 receptor in the myenteric plexus may represent the morphological correlate of the clinical target of teduglutide in Crohn's disease.

Eosinophils in the gastrointestinal tract: friends or foes?

Eosinophils play an important role in the mucosal immune system of the gastrointestinal tract under resting and under inflammatory conditions. Under steady-state conditions, the mucosa of the digestive tract is the only organ harboring a substantial number of eosinophils, which, if need be, get activated and exert several effector and immunoregulatory functions. The precise function of these late-phase inflammatory cells is not yet completely understood. Nevertheless, it has recently been demonstrated that lipopolysaccharides from gram-negative bacteria activate eosinophils to rapidly release mitochondrial DNA in the extracellular space. Released mitochondrial DNA and eosinophil granule proteins form extracellular structures able to bind and inactivate bacteria. These findings suggest a novel mechanism of eosinophil-mediated innate immune responses that might be important in maintaining the intestinal barrier function. Moreover, eosinophils also play a crucial role in several inflammatory conditions, such as intestinal infections, immune-mediated inflammations and hypersensitivity reactions. Under chronic inflammatory conditions, the ability of the eosinophils to induce repair can lead to pathological sequelae in the tissue, such as esophageal remodeling in eosinophilic esophagitis. It is established that the uncontrolled eosinophilic inflammation induces fibrosis, esophageal wall thickening and strictures leading to damage that results in a loss of esophageal function. One potential mechanism of this remodeling is so-called 'epithelial mesenchymal transition', which is triggered by eosinophils and is potentially reversible under successful anti-eosinophil treatment. Therefore, eosinophils may act either as friends or as foes, depending on the microenvironment.

Binding sites of muscarinic and adrenergic receptors in gastrointestinal tissues of dairy cows suffering from left displacement of the abomasum

Muscarinic acetylcholine (M) and adrenergic (AR) receptors mediate gastrointestinal motility. Using radioligand binding assays and real-time polymerase chain reaction, the densities of binding sites and mRNA levels of M(2), M(3), alpha(2AD)- and beta(2)-AR were compared in muscle tissues from the abomasal fundus, pylorus, duodenum, caecum, and external loop of the spiral colon of eight cows with left displacement of abomasum (LDA), and of eight healthy cows. Specific binding of the [(3)H]-ligands to each of the four receptors was competitive and saturable. Binding sites of M(2) (all intestinal sites), M(3) (duodenum and caecum), and of alpha(2AD)-AR (abomasal fundus) were lower (P<0.05) in cows with LDA than in healthy cows. The coefficients of correlation between binding sites and mRNA transcripts of receptors were dissimilar in cows with LDA and healthy cows. The decrease in densities of M (intestine) and of alpha(2AD)-AR (abomasum) receptors suggests their implication in the impairment of motility associated with or leading to LDA.

Gender-specific elimination of continuous-infusional 5-fluorouracil in patients with gastrointestinal malignancies: results from a prospective population pharmacokinetic study

This study was initiated to assess the quantitative impact of patient anthropometrics and dihydropyrimidine dehydrogenase (DPYD) mutations on the pharmacokinetics (PK) of 5-fluorouracil (5FU) and to explore limited sampling strategies of 5FU.

Distribution of muscarinic receptor subtypes and interstitial cells of Cajal in the gastrointestinal tract of healthy dairy cows

OBJECTIVE: To describe the distribution of muscarinic receptor subtypes M(1) to M(5) and interstitial cells of Cajal (ICCs) in the gastrointestinal tract of healthy dairy cows. SAMPLE POPULATION: Full-thickness samples were collected from the fundus, corpus, and pyloric part of the abomasum and from the duodenum, ileum, cecum, proximal loop of the ascending colon, and both external loops of the spiral colon of 5 healthy dairy cows after slaughter. PROCEDURES: Samples were fixed in paraformaldehyde and embedded in paraffin. Muscarinic receptor subtypes and ICCs were identified by immunohistochemical analysis. RESULTS: Staining for M(1) receptors was found in the submucosal plexus and myenteric plexus. Antibodies against M(2) receptors stained nuclei of smooth muscle cells only. Evidence of M(3) receptors was found in the lamina propria, in intramuscular neuronal terminals, on intermuscular nerve fibers, and on myocytes of microvessels. There was no staining for M(4) receptors. Staining for M(5) receptors was evident in the myocytes of microvessels and in smooth muscle cells. The ICCs were detected in the myenteric plexus and within smooth muscle layers. Distribution among locations of the bovine gastrointestinal tract did not differ for muscarinic receptor subtypes or ICCs. CONCLUSIONS AND CLINICAL RELEVANCE: The broad distribution of M(1), M(3), M(5), and ICCs in the bovine gastrointestinal tract indicated that these components are likely to play an important role in the regulation of gastrointestinal tract motility in healthy dairy cows. Muscarinic receptors and ICCs may be implicated in the pathogenesis of motility disorders, such as abomasal displacement and cecal dilatation-dislocation.