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Results for “Intestinal Barrier Function”

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At least 1,225 records · Page 68Linked to original sources
PubMed1994

Abnormal leukotriene C4 released by unaffected jejunal mucosa in patients with inactive Crohn's disease.

The mucosal release of inflammatory mediators is enhanced in active inflammatory bowel disease. This study examines whether leukotriene C4 production occurs in apparently unaffected segments of the gut. The intraluminal release of leukotriene C4 was determined by jejunal perfusion in seven healthy controls, in nine patients with chronic ulcerative colitis, and in 13 patients with Crohn's disease (six with ileal disease, and seven with only colonic). All patients were in clinical remission and none of them had evidence of jejunal involvement. Mild intraluminal irritation with a 2.5 mmol/l deoxycholic acid solution was induced to stimulate local inflammatory mechanisms. The release of DNA (a marker of mucosal desquamation) and prostaglandin E2 (PGE2) was simultaneously measured. Jejunal release of DNA was higher in Crohn's disease patients than in ulcerative colitis or healthy controls. Basal release of PGE2 was similar in the three groups of patients. Basal release of leukotriene C4 was considerably enhanced, however, in Crohn's disease patients compared with healthy controls. In ulcerative colitis patients, basal leukotriene C4 release was non-significantly different from controls. Bile acid perfusion stimulated PGE2, leukotriene C4, and DNA release in all groups studied, but leukotriene C4 release was significantly higher in Crohn's disease patients. It is concluded that in inactive Crohn's disease there is an enhanced intraluminal release of leukotriene C4 in apparently unaffected segments of proximal small bowel, which may reflect fundamental changes in the function of the gut mucosal barrier.

Adult↗
PubMed1990

Duration of absorption-enhancing effect of sodium octanoate, sodium hexanoate or glyceryl-1-monooctanoate on rectal absorption of gentamicin in rabbits.

The duration of the absorption-enhancing effect of sodium octanoate (C8), sodium hexanoate (C6) and glyceryl-l-monooctanoate (MO) on the rectal absorption of gentamicin (GM) using the hollow-type suppository was investigated in rabbits. To evaluate the duration of the absorption-enhancing effect by pretreatment (treatment of absorption enhancer before GM administration), suppository I containing each absorption enhancer in the cavity was administered into the rectum. Then suppository II containing GM in the cavity was administered at predetermined times (0.33, 2, 6 and 24 h) after the administration of suppository I. Plasma GM levels obtained by the pretreatment with absorption enhancer were compared with those obtained by the simultaneous administration of GM with absorption enhancer. The AUC and Cmax of GM significantly decreased with the pretreatment of C8 (6 and 24 h), C6 (2 and 6 h) or MO (6 and 24 h) before rectal GM administration, as compared with the simultaneous administration of GM with C8, C6 or MO. A marked decrease in the absorption-enhancing effect of C8, C6 and MO on rectal GM absorption was observed by the prolongation of the period between the pretreatment of each absorption enhancer and GM administration. The duration of the absorption-enhancing effect of C6 was shorter than that of C8, whereas this duration of MO was similar to that of C8. The effect of these absorption enhancers disappeared 24 h after the pretreatment. These results suggested that the lowering of the membrane transport barrier function recovered about one day after the administration of C8 or MO.

Administration, Rectal↗
PubMed2006

Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis.

Crohn's disease and ulcerative colitis are idiopathic, chronic, relapsing, inflammatory conditions that are immunologically mediated. Although their exact etiologies remain uncertain, results from research in animal models, human genetics, basic science and clinical trials have provided important new insights into the pathogenesis of chronic, immune-mediated, intestinal inflammation. These studies indicate that Crohn's disease and ulcerative colitis are heterogeneous diseases characterized by various genetic abnormalities that lead to overly aggressive T-cell responses to a subset of commensal enteric bacteria. The onset and reactivation of disease are triggered by environmental factors that transiently break the mucosal barrier, stimulate immune responses or alter the balance between beneficial and pathogenic enteric bacteria. Different genetic abnormalities can lead to similar disease phenotypes; these genetic changes can be broadly characterized as causing defects in mucosal barrier function, immunoregulation or bacterial clearance. These new insights will help develop better diagnostic approaches that identify clinically important subsets of patients for whom the natural history of disease and response to treatment are predictable.

Animals↗
PubMed2002

Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress.

Intestinal dysfunction is related to stress and early life events, but the mechanisms are largely unknown. Our aim was to determine whether early trauma predisposes adult rats to intestinal mucosal dysfunction in response to stress. Neonatal Sprague-Dawley rats were individually separated from their mothers for 3 h/day at 4-21 days of age. Between days 80 and 90, separated and control rats were subjected to mild acute stress (30-min water avoidance) or sham stress. Mucosal barrier function and ion transport were assessed in colonic tissues mounted in Ussing chambers. Mild stress increased short-circuit current, conductance, and transepithelial transport of macromolecules in separated rats, while having minimal effects in controls. Pretreatment of the separated rats with a corticotropin-releasing hormone (CRH) antagonist, the peptide alpha-helical CRH(9-41) injected intraperitoneally 20 min before stress, abolished the stress-induced mucosal changes. Our results indicate that neonatal trauma can induce phenotypic changes in adulthood, including enhanced vulnerability of the gut mucosa to stress via mechanisms involving peripherally located CRH receptors.

Animals↗
PubMed2003

Cellular signaling in rapid intestinal epithelial restitution: implication of polyamines and K+ channels.

Epithelial cells line the gastrointestinal (GI) mucosa and form an important barrier that protects the subepithelial tissue against a wide array of noxious substances, allergens, viruses, and luminal microbial pathogens. Restoration of mucosal integrity following injury requires epithelial cell decisions that regulate signaling networks controlling gene expression, survival, migration, and proliferation. Over the past few years, polyamines have been shown to play a critical role in GI mucosal repair, and the control of cellular polyamines is a central convergence point for the multiple signaling pathways. Both the function of polyamines in rapid intestinal mucosal epithelial restitution and the underlying mechanism, especially the implication of K(+) channel activity, are the subject of this mini-review article.

Animals↗
PubMed1999

Hemorrhagic shock results in intestinal muscularis intercellular adhesion molecule (ICAM-1) expression, neutrophil infiltration, and smooth muscle dysfunction.

Intestinal stasis followed by mucosal barrier breakdown and the generation of locally produced cytokines has been proposed as the cause of systemic infection and multiple organ failure following hemorrhagic shock. The aim of this study was to investigate the underlying mechanisms of impaired intestinal muscle function leading to ileus following hemorrhagic shock. Rats were subjected to severe hemorrhagic shock (mean arterial pressure 40 mm Hg) followed by resuscitation and were killed early at 4 h or late at 24 h. Other groups consisted of control and sham animals. Intercellular adhesion molecule (ICAM-1) mRNA levels were significantly elevated in the muscularis but not in the mucosa using the semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). There was a marked infiltration of neutrophils into the muscularis early and late after shock. Furthermore, smooth muscle contractility in response to bethanechol was significantly decreased, being more pronounced in the early group. Immunohistochemistry revealed signal for ICAM-1 in the muscularis microvasculature and on infiltrating cells. These results suggest that the expression of ICAM-1 within the muscularis vasculature after hemorrhagic shock promotes the local recruitment of leukocytes and that this inflammatory response is accompanied by a subsequent impairment of intestinal contractility.

Animals↗
PubMed1997

The intestinal epithelial cell: immunological aspects.

IECs likely play an important role in immunological defense mechanism. Apart from being a passive barrier against luminal bacteria, IECs secrete protective and microbiocidal products such as ITF, complement components and cryptdins into the lumen. Moreover, IECs produce secretory component that is essential for the transport of IgA from the lamina propria into the lumen. IECs also have regulatory functions. They express adhesion molecules important in the homing of T cells and other leukocytes, and likely modulate T cell functions in a paracrine way. Furthermore, IECs secrete cytokines, either constitutively or after bacterial challenge, and they express cytokine receptors. Lastly, IECs may play an important role as non-professional antigen-presenting cells by expressing classical MHC class I and class II and nonclassical MHC class I molecules on the cell surface. This aspect is particularly intriguing in that IECs also express a FcR that may have a function in luminal antigen sampling.

Animals↗
PubMed2000

[Protection of the mucosal barrier by nutritional strategies. What are the therapeutic options?].

The dysfunction of intestinal barrier allows the translocation of both endotoxin and whole bacterial organisms. It plays an important role in the development of multiple organ failure (MOF). The mucosa ia one component of this barrier. Trauma, atrophy and the "systemic inflammatory response syndrome" increase gastrointestinal permeability. These abnormalities may contribute to the pathophysiology of sepsis. Malnutrition per se compromises the gut's barrier function. Maintenance of gastrointestinal blood flow may be facilitated by (glutamine-enriched?) enteral diets. The most important conclusions of the majority of controlled trials support the concept of the very early enteral nutrition (within 24 hours after trauma): the outcome of seriously ill patients is improved, the rate of complications and infections is reduced. Gastrointestinal motility disorders may interfere with the initiation and tolerance of early enteral nutrition. They may be managed by prokinetic agents (cisapride, erythromycin) or by bypassing the stomach with a nasoenteric tube.

Gastrointestinal Diseases↗
PubMed1980

Biotransformational and neurophysiological changes in rabbits exposed to lead.

Lead was administered to adult male rabbits in drinking water at a 0.1% concentration for four and five week periods. The lead contents were determined in the central and peripheral nervous tissues and in the liver, kidney, and intestinal mucosa. The conduction velocity of sciatic nerve and the activities of drug metabolizing enzymes in other tissues were determined. The lead concentration in the blood was at a steady state at four to five weeks of exposure. Lead accumulated in all tissues except the brain. The brain lead concentration was 40 to 50% of that in the blood, indicating the existence of a blood-brain barrier. However, the lead concentration in the sciatic nerve increased significantly from four to five weeks of exposure and exceeded that in the blood. This indicates the lack of a blood-nervous tissue barrier in the sciatic nerve allowing a continuous accumulation of lead. This accumulation affected the function of the sciatic nerve; motor nerve conduction velocity decreased from the control level (58.3 +/- 7.4 m/sec) to 43.8 +/- 6.3 m/sec after the four-week exposure and to 35.0 +/- 1.3 m/sec at 5 weeks of exposure. After five weeks of exposure, no changes in the hepatic, intestinal, or renal drug metabolizing enzyme activities were found. These results suggest that motor nerve conduction velocity is affected by lead exposure prior to any influence on biotransformation enzymes.

Animals↗
PubMed2001

Acid stimulates E-cadherin surface expression on gastric epithelial cells to stabilize barrier functions via influx of calcium.

BACKGROUND AND AIMS: E-cadherin, which is a [Ca2+]-dependent, homotypic cell-cell adhesion molecule, is expressed in gastrointestinal epithelial cells. Much has been learned about the down-regulation of E-cadherin expression in gastrointestinal tumours, Barrett's oesophageal dysplasia, and Crohn's disease, but the functions of this molecule in normal gastrointestinal mucosa are less known. METHODS: In this study, we investigated the relationship between E-cadherin expression and permeability using rat cultured gastric and intestinal epithelial cells following a 30-min exposure to various pH solutions. We also investigated the participation of [Ca2+] in these events. RESULTS: E-cadherin expression increased under acid (pH 4) but not alkali (pH 10 or 11) exposure only for gastric epithelial cells. Gastric epithelial permeability was maintained only against acid exposure while intestinal permeability increased under both conditions. Transient influx of [Ca2+] was only observed for gastric epithelial cells just after acid exposure. CONCLUSIONS: These findings suggest that E-cadherin expression on gastric epithelium stabilizes the epithelial barrier against acid, probably through influx of [Ca2+]. This event is thought to be one of the protective mechanisms in gastric mucosa against acid back-diffusion, which is one of the causes of peptic ulcer formation.

Acids↗
PubMed1993

Nitric oxide release in response to gut injury.

We evaluated nitric oxide release in several models of intestinal inflammation through luminal nitrite concentrations. In anesthetized rabbits, piglets, and guinea pigs, luminal lavages were collected from loops of normal or injured small intestine. Lavages were analyzed spectrophotometrically for nitrite (Griess reagent) and protein. Myeloperoxidase (MPO) content of intestinal segments was used as an index of granulocyte infiltration and intestinal inflammation. Acute ileal inflammation was induced by luminal acetic acid + casein in rabbits and luminal deoxycholate in neonatal piglets and adult rabbits. Chronic ileitis was induced in guinea pigs by intraluminal trinitrobenzenesulfonic acid. In each model nitrite levels in ileal lavages were significantly greater than control loops/animals. Increased luminal protein and intestinal MPO activity paralleled the changes in nitrite levels. To determine whether nitric oxide production influenced mucosal repair, segments of ileum were perfused with the L-arginine antagonist NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/ml) after acute acetic acid + casein exposure. L-NAME administration reversed the decline in epithelial permeability characteristic of epithelial restitution, causing an increase in epithelial permeability which was readily reversible. These results suggest that nitrite production is a useful index of gut injury and that nitric oxide may contribute to the functional repair of the epithelial barrier under acute conditions.

Animals↗
PubMed1997

Bacteroides fragilis toxin exhibits polar activity on monolayers of human intestinal epithelial cells (T84 cells) in vitro.

Strains of Bacteroides fragilis associated with diarrhea in children (termed enterotoxigenic B. fragilis, or ETBF) produce a heat-labile ca. 20-kDa protein toxin (BFT). The purpose of this study was to examine the activity of BFT on polarized monolayers of human intestinal epithelial cells (T84 cells). In Ussing chambers, BFT had two effects. First, BFT applied to either the apical or basolateral surfaces of T84 monolayers diminished monolayer resistance. However, the time course, magnitude, and concentration dependency differed when BFT was applied to the apical versus basolateral membranes. Second, only basolateral BFT stimulated a concentration-dependent and short-lived increase in short circuit current (Isc; indicative of C1- secretion). Time course experiments indicated that Isc returned to baseline as resistance continued to decrease, indicating that these two electrophysiologic responses to BFT are distinct. Light microscopic studies of BFT-treated monolayers revealed only localized cellular changes after apical BFT, whereas basolateral BFT rapidly altered the morphology of nearly every cell in the monolayer. Transmission and scanning electron microscopy after basolateral BFT confirmed a striking loss of cellular microvilli and complete dissolution of some tight junctions (zonula occludens) and zonula adherens without loss of desmosomes. The F-actin structure of BFT-treated monolayers (stained with rhodamine-phalloidin) revealed diminished and flocculated staining at the apical tight junctional ring and thickening of F-actin microfilaments in focal contacts at the basolateral monolayer surface compared to those in similarly stained control monolayers. BFT did not injure T84 monolayers, as assessed by lactic dehydrogenase release and protein synthesis assays. These studies indicate that BFT is a nonlethal toxin which acts in a polar manner on T84 monolayers to stimulate C1- secretion and to diminish monolayer resistance by altering the apical F-actin structure of these cells. BFT may contribute to diarrheal disease associated with ETBF infection by altering epithelial barrier function and stimulating C1- secretion.

Actins↗
PubMed2005

Innate immune relationship between commensal flora and the mammalian intestinal epithelium.

Commensal bacteria in the lumen of the intestine exist in a mutually advantageous relationship with the mammalian host, providing benefits such as increased metabolic/digestive capabilities and exclusion of harmful microbes, and in turn receiving a nutrient-rich environment. However, in the context of a dysfunctional intestinal epithelial barrier, commensal bacteria may elicit an immune inflammatory response similar to what occurs during infection by a pathogen. Recent work has established that most eukaryotic cells possess families of receptors that can detect the structural signatures of prokaryotic life. Cells may respond to the perception of microbes by activating distinct cytoplasmic signaling cascades that ultimately result in the transcriptional activation of genes needed for proinflammatory and anti-apoptotic functions, as well as for a pro-apoptotic response. Collectively, these responses generally suffice to eliminate microbial threats and may be integral to normal intestinal homeostasis. An understanding of these mechanisms, as well as those by which microbes themselves influence intestinal epithelial responses, may help provide a new perspective on the pathogenesis of intestinal diseases.

Animals↗
PubMed1977

Midgut ultrastructure of Culex tarsalis (Diptera: Culcidae) before and after a bloodmeal.

The midgut ultrastructure of rasin-and blood-fed female mosquitoes, Culex tarsalis Coquillentt, was examined. The raisin-fed midgut is characterized by: (1) large nuclei, (2) small mitochondria, (3) short segments of rough endoplasmic reticulum, (4) rough endoplasmic reticular vesicular vesicles in the posterior midgut only, and (5) increased autophagic acitivity with age. Blood feeding elicits drastic changes in midgut epithelial structures: (1) nuclei are smaller, (2) mitochondria are much enlarged, (3) rough endoplasmic reticular vesicles disappear, (4) rough endoplasmic reticular whorls appear, (5) residual lyosomal figures are abundant, and (6) an intercellular accumulation of an electron-opaque material is noted. The significance of rough endoplasmic reticular whorls and vesicles in bloodmeal digestion is discussed. In addition, the concept of a functional host 'gut barrier' to infection by pathogens is examined as related to a possible by-pass mechanism.

Animals↗
PubMed2000

VIP enhances the differentiation of retinal pigment epithelium in culture: from cAMP and pp60(c-src) to melanogenesis and development of fluid transport capacity.

The retinal pigment epithelium (RPE) is a single cell layer juxtaposed between the neural retina and the choroid and functions as a blood-retina barrier. The RPE performs functions essential for photoreceptor (PR) survival. Although the regulation of these functions has remained unknown, it is a distinct possibility that the RPE is under constant regulation by signaling molecules coming from the choroid and the retina. Vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide present in the retina and in the choroid, has been shown to promote the growth and differentiation of a variety of cells in tissue and organ cultures. In cultured RPE cells, VIP is the one most effective stimulator of the cAMP signaling pathway among a long list of neurotransmitters and modulators tested. For example, VIP, at 1 microM, stimulates the intracellular cAMP to 80-100- and 20-fold in 3 min in RPE cells cultured from chick embryos and adult human donor eyes, respectively. In cultured chick embryonic RPE, VIP is also shown to be a potent and effective modulator of pp60(c-src), the non-receptor tyrosine kinase present in differentiating and terminally differentiated cells. VIP stimulates both overall phosphorylation at unknown sites and phosphotyrosine dephosphorylation in pp60(c-src). A 190-kDa microtubule-associated protein is known to be one of the downstream targets in VIP-modulated signaling pathways. At the cellular level, VIP stimulates cell proliferation modestly and melanogenesis pronouncedly in growing chick embryonic RPE cultures. Ultimately, the differentiation goal of RPE cells in vivo is to perform functions that are essential for photoreceptor survival. On bare permeable supports (that is, without biological material coating), the chick embryonic RPE cells grow to become RPE sheets with a cytoarchitecture that allows the display of two of the RPE functions. These cultures demonstrate structural polarity and are functionally polarized, allowing for proper macromolecule secretion and fluid transport. VIP is shown to stimulate macromolecule secretion at the apical surface (retina facing) and the development of the capacity for fluid transport from the apical to the basal surface of the RPE sheet. In conclusion, studies in our laboratory indicate that VIP is a differentiation promotor during the development of a functional RPE. Recent advances in the molecular biology of melanogenesis and the fluid transport-linked Na-K-2Cl cotransporter in other cells will allow future studies of VIP modulated events in the RPE at the molecular level. Finally, identification of RPE differentiation factors may prove essential for the ultimate success of RPE transplantation, thus promoting the rescue of photoreceptor cells in retinal degeneration.

Animals↗
PubMed1998

Nutritional modulation of gut inflammation.

Nutritional therapy is an important component of the management of gastrointestinal inflammation, which disrupts the gut mucosal barrier leading to sepsis, SIRS and MODS. Future studies will be needed to define the role of specific nutrients in enhancing mucosal barrier function and supporting general immune function, and how this affects morbidity and mortality of critically-ill patients.

Animals↗
PubMed2005

HB-EGF enhances restitution after intestinal ischemia/reperfusion via PI3K/Akt and MEK/ERK1/2 activation.

BACKGROUND & AIMS: Early recovery of intestinal function after injury occurs by restitution, a complex process with a poorly understood molecular basis. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent chemotactic factor that is induced during ischemia/reperfusion in vivo and intestinal wounding in vitro. The role of HB-EGF in intestinal restitution and the underlying intracellular signaling pathways involved were investigated. METHODS: Adult rats were subjected to intestinal ischemia, with histologic and biochemical damage assessed during the first 3 hours of reperfusion. The effect of recombinant HB-EGF (rHB-EGF) on structural and functional recovery of the intestine by restitution was evaluated in vivo. Scrape wounding of intestinal epithelial cell monolayers was used to elucidate the mechanisms of intrinsic and rHB-EGF-induced restitution. RESULTS: Early structural recovery occurred within 3 hours of reperfusion and was attributed to restitution rather than proliferation. HB-EGF treatment significantly improved structural recovery and accelerated functional recovery of the gut barrier. In vivo restitution was preceded by activation of Akt and extracellular signal-regulated kinase (ERK) 1/2, which were accelerated and enhanced by HB-EGF treatment. Blocking of ErbB-1, phosphatidylinositol 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase/ERK kinase (MEK)/ERK activity resulted in significant reduction in intrinsic and HB-EGF-induced restitution in vitro. Endogenous HB-EGF was shown to play an essential role in wound-induced ErbB-1 and ERK1/2 activation and in intrinsic restitution. CONCLUSIONS: Endogenous HB-EGF, ErbB-1, PI3K/Akt, and MEK/ERK are involved in intrinsic restitution. rHB-EGF enhances restitution in vivo and in vitro in a PI3K/Akt- and MEK/ERK1/2-dependent fashion.

Animals↗