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At least 109 records · Page 6Linked to original sources
PubMed1997

Mucosal injury and disruption of intestinal barrier function in HIV-infected individuals with and without diarrhea and cryptosporidiosis in northeast Brazil.

OBJECTIVES: To determine the relative effects of AIDS-related diarrhea with or without cryptosporidiosis and microsporidiosis on intestinal function and injury. METHODS: We studied 40 HIV-infected patients (20 with and 20 without diarrhea) and 13 healthy volunteers, using the differential urinary excretion of ingested lactulose and mannitol as respective markers of barrier disruption and overall villous surface area. We also examined them for fecal leukocytes, lactoferrin, and alpha 1-antitrypsin. Fasting subjects drank test solution containing lactulose (5 g) and mannitol (1 g). Urine was collected for 5 h and tested for sugars by high-performance liquid chromatography with pulsed amperometric detection. RESULTS: HIV-positive patients with diarrhea had a 2.8-fold higher lactulose:mannitol excretion ratio (L:M) than HIV-positive patients without diarrhea (p = 0.01) and 10.4-fold higher than healthy volunteers (p = 0.004). This was accounted for by a 1.5- to 3.1-fold higher rate of lactulose excretion by HIV patients with diarrhea than by those without diarrhea or by healthy volunteers. Mannitol excretion was 32-55% less in patients with diarrhea than in those without diarrhea or in healthy volunteers. Patients with cryptosporidial diarrhea had a nearly 6-fold higher L:M ratio than those without diarrhea (p < 0.001) and nearly 3-fold higher than those with non-cryptosporidial diarrhea (p = 0.02). One patient with microsporidial infection had a nearly 3-fold higher L:M ratio than controls without diarrhea. Alpha 1-Antitrypsin was positive in 40% of HIV-positive patients with cryptosporidial infections and none of 12 HIV-positive patients with non-cryptosporidial diarrhea. Fecal lactoferrin or leukocytes were increased in all HIV patients with diarrhea. CONCLUSION: HIV infection is associated with intestinal dysfunction and injury, even in patients who do not have diarrhea. However, those with diarrhea, especially with cryptosporidiosis or microsporidiosis, have even greater disruption of intestinal barrier function with potentially important nutritional consequences.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Intestinal barrier to intact horseradish peroxidase in experimental secretory diarrhea.

Intestinal permeability to intact horseradish peroxidase (HRP, MW 40,000) was assessed during the acute phase of secretory diarrhea. Secretion was either induced in ligated loops of rabbit jejunum with cholera toxin or mimicked in vitro with db-cAMP, 8Br-cGMP, or theophylline in isolated fragments of rabbit jejunum mounted in Ussing chambers. Although intestinal electrolyte secretion was obtained under these conditions, as shown by the rises in short-circuit current and potential difference, jejunal permeability to HRP did not change. These results suggest that, throughout the time course of secretory diarrhea, no change occurs in the functional ability of the jejunal epithelium to protect the organism against massive intact protein penetration.

Animals↗
PubMed1995

[Effects of dietary fat on permeability of the protective intestinal barrier to macromolecules in experimental anaphylaxis].

Wistar rats were sensitized with hen egg ovalbumin (OVA) intraperitoneally and were fed with diets that contained 12% fish oil (FO) or sunflower oil for 3 weeks with a purpose to study the influence of dietary fat source on the macromolecular permeability of small intestine in systemic anaphylaxis. 29 days later the systemic anaphylaxis was challenged by i.v. administration of OVA. This reaction was aggravated in animals fed with FO this being supported by morphofunctional changes pattern in small intestine. The deleterious effect on intestinal protective barrier efficiency against polyethyleneglycol 4000 macromolecules was noticed in rats fed with FO containing large amounts of n-3 PUFA. It's suggested that the prevention of deleterious effect of FO is possible by increase of dietary antioxidative factors consumption that might be taken into consideration during some kinds of dietary treatment.

Anaphylaxis↗
PubMed1991

Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure.

The intestinal mucosa plays a fundamental role as the site for absorption of nutrients, and as an important barrier from potentially harmful agents in the intestinal lumen. Little is known of the permeability properties of the intestinal mucosa in uraemic patients. The intestinal permeability to differently sized polyethylene glycols (PEGs; range 326-1254 daltons) was studied in nine patients with chronic renal failure (24 hour endogeneous creatinine clearance 5-24 ml/minute). The maximum 24 hour urinary recovery of PEGs was decreased in the uraemic patients but relatively more of the larger than the smaller PEGs were found in these patients. The results suggest a reduced urinary recovery of PEGs caused by renal dysfunction but also a relatively increased intestinal permeability to larger PEGs in the uraemic patients.

Adult↗
PubMed2005

Mechanisms of nitric oxide-mediated intestinal barrier failure in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is the leading intestinal emergency in premature infants. The underlying etiology of NEC remains elusive, but hypoxic conditions and early enteral feeding are consistently implicated as the main risk factors in the pathogenesis of NEC. We postulate that nitric oxide (NO) plays a key role as a molecular signaling "hub" in the generation of gut barrier failure in NEC. Clinical studies suggest that inflammatory cytokines and excessive NO production may contribute to the pathogenesis of NEC. One of the major challenges in defining the critical signaling pathways that lead to the development of NEC is the lack of specific biochemical markers that consistently delineate the early stages of NEC. Intestinal pathology and molecular markers derived from late-stage NEC represent end-stage findings and thus provide little insight into the early events that led to intestinal inflammation. Such markers may not represent viable therapeutic targets for the treatment or prevention of NEC. Therefore, novel strategies are needed to identify the patients at risk for NEC and define the clinically relevant molecules that characterize the early stages of NEC. This review will examine the mechanisms of NO-mediated gut barrier failure and propose novel genetic-based approaches for elucidating the critical molecular pathways in NEC.

Enterocolitis, Necrotizing↗
PubMed2006

Effects of the pesticide clorpyrifos on an in vitro model of intestinal barrier.

Clorpyrifos (CPF), one of the most widely used organophosphorothionate pesticide can be detected as residues in food and drinking water; therefore the oral route is the major route of exposure for the general population, including children, following household use of this insecticide. Aim of this work was to investigate the possible acute cytotoxic effects of CPF on intestine and the integrity of the epithelial barrier, using Caco-2/TC7 cells as intestinal in vitro model. High level of CPF found inside the cells, corresponding to about 80% of the nominal concentration tested (30, 50 and 250microM), chosen as representative of the concentrations attainable in the intestinal lumen after actual levels of human oral exposure. In these conditions, no cytotoxicity in terms of cellular viability was observed. However, at the highest CPF nominal concentration (250microM) the impairment of barrier integrity was evidenced, due only to the parent compound, since no CPF metabolites could be detected in our experimental conditions. CPF itself was demonstrated to interfere with the tight junction on this in vitro model of epithelial intestinal cells, altering the barrier integrity and very likely the absorption of other co-administered chemicals.

Caco-2 Cells↗
PubMed1999

Nitric oxide and intestinal barrier failure.

The systemic inflammatory response syndrome (SIRS) is a leading cause of morbidity and mortality in adults and children. Various proinflammatory mediators have been implicated in the pathogenesis of SIRS; however, their mechanisms of action are poorly defined. Recent evidence suggests that nitric oxide (NO) plays a regulatory role in gut barrier function. Sustained upregulation of NO production in the intestine can lead to intestinal epithelial injury through the formation of peroxynitrite. Peroxynitrite can nitrate mitochondrial proteins and inhibit cellular respiration. The resultant changes in mitochondrial function lead to activation of the caspase cascade, subsequent DNA fragmentation, and enterocyte apoptosis. Enterocyte apoptosis results in a transient "bare area" in the intestinal epithelium where bacteria can attach and then penetrate the lamina propria. Bacteria that successfully escape the immune system may in turn incite a systemic inflammatory response.

Apoptosis↗
PubMed2005

Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins.

Coeliac disease is a chronic enteropathy caused by the ingestion of wheat gliadin and other cereal prolamines derived from rye and barley. In the present work, we investigated the mechanisms underlying altered barrier function properties exerted by gliadin-derived peptides in human Caco-2 intestinal epithelial cells. We demonstrate that gliadin alters barrier function almost immediately by decreasing transepithelial resistance and increasing permeability to small molecules (4 kDa). Gliadin caused a reorganisation of actin filaments and altered expression of the tight junction proteins occludin, claudin-3 and claudin-4, the TJ-associated protein ZO-1 and the adherens junction protein E-cadherin.

Actins↗
PubMed1996

Effects of hypoperfusion on small-intestinal mucosal morphology and intestinal barrier function.

BACKGROUND: Our aim was to evaluate in vitro perfusion of the rat small intestine as a method to study the pathophysiology of hypoperfusion and to minimize its adverse effects. METHODS: Rat small intestine was perfused for 24 h using RPMI + albumin for the lumen and RPMI + erythrocyte concentration (Hct 20%) in the vasculature, at 22 degrees C, 15 degrees C, 10 degrees C, and 6 degrees C. The outcome was evaluated by histologic grading and permeability for polyethylene glycol 900 (PEG 900). RESULTS: Perfusion of the intestine at 6 degrees C resulted in lower degree of mucosal damage and permeation of PEG 900, compared with storage and perfusion at higher temperatures. CONCLUSIONS: In vitro perfusion of the small intestine, using histologic grading of mucosal lesions and permeation of PEG 900 as indicators, is one method that can be applied to study the pathophysiology of intestinal hypoperfusion. Perfusion at 6 degrees C significantly reduced the level of damage to the intestinal mucosa.

Animals↗
PubMed1998

Disruption of intestinal barrier function associated with experimental colitis: possible role of mast cells.

The objective was to characterize changes in barrier and transport function in an experimental model of colitis, and to determine whether mast cells contribute to these changes. Colitis was induced in rats with intracolonic 2,4,6-trinitrobenzenesulfonic acid (TNBS, 30 mg) in 50% ethanol. Controls received 0.9% saline or the ethanol vehicle alone. In vivo loop perfusion was used to assess colonic water flux (in microliter.cm-1.h-1) and lumen-to-blood 51Cr-labeled EDTA clearance (% administered dose) after TNBS. Myeloperoxidase (MPO) was used as an index of granulocyte influx. TNBS or its vehicle caused a marked decrease in water absorption and an increase in permeability at 4 h after administration compared with saline. Neither dexamethasone (anti-inflammatory control) nor doxantrazole (mast cell stabilizer) was able to attenuate these early changes likely caused by the vehicle. In contrast, at later times, TNBS (but not its vehicle) also increased 51Cr-EDTA permeability and decreased water absorption; both effects were significantly attenuated by dexamethasone or doxantrazole. These drugs also significantly reduced TNBS-induced MPO accumulation and release of rat mast cell protease II. We conclude that experimental colitis is associated with severe defects in intestinal transport and barrier functions and that mast cells may contribute to the pathogenesis of these changes.

Animals↗
PubMed2003

Growth faltering in rural Gambian infants is associated with impaired small intestinal barrier function, leading to endotoxemia and systemic inflammation.

Growth faltering of rural Gambian infants is associated with a chronic inflammatory enteropathy of the mucosa of the small intestine that may impair both digestive/absorptive and barrier functions. The aim of this study was to determine whether the enteropathy was associated with a compromised barrier function that allowed translocation of antigenic macromolecules from the gut lumen into the body, with subsequent systemic immunostimulation, resulting in growth retardation. Rural Gambian infants were studied longitudinally at regular intervals between 8 and 64 wk of age. On each study day, each child was medically examined, anthropometric measurements were made, a blood sample was taken and an intestinal permeability test performed. Evidence of chronic immunostimulation was provided by abnormally elevated white blood cell, lymphocyte and platelet counts, and frequently raised plasma concentration of C-reactive protein. Intestinal permeability was abnormal and associated with impaired growth (r = -0.41, P < 0.001). Plasma concentrations of endotoxin and immunoglobulin (Ig)G-endotoxin core antibody were also elevated and related to both growth (r = -0.30, P < 0.02; r = -0.64, P < 0.0001, respectively) and measures of mucosal enteropathy. Plasma IgG, IgA and IgM levels increased rapidly with age toward adult concentrations. Raised values were related to poor growth but also to measures of mucosal enteropathy and the endotoxin antibody titer. The interrelationships among these variables and growth suggested that they were all part of the same growth-retarding mechanism. These data are consistent with the hypothesis of translocation of immunogenic lumenal macromolecules across a compromised gut mucosa, leading to stimulation of systemic immune/inflammatory processes and subsequent growth impairment.

Body Height↗
PubMed2001

The mycotoxin ochratoxin A alters intestinal barrier and absorption functions but has no effect on chloride secretion.

Ochratoxin A (OTA) is a mycotoxin that contaminates cereals and animal feed and causes nephropathy to a variety of animal species. OTA is also known as a potent immunotoxic, teratogenic, and carcinogenic mycotoxin. In addition, OTA ingestion induces intestinal injuries, including inflammation and diarrhea. With the aim to study the cellular mechanisms associated with the intestinal toxicity of OTA, two human epithelial intestinal cell lines (HT-29-D4 and Caco-2-14 cells), widely used as in vitro models for the intestinal epithelium, were incubated with OTA. The main effects of the mycotoxin were an inhibition of cellular growth and a dramatic decrease of transepithelial resistance in both cell lines. Since transepithelial resistance reflects the organization of tight junctions over the cell monolayer, these data may suggest that OTA could potentiate its own absorption through paracellular pathways. OTA induced a 60% decrease of sodium-dependent glucose absorption but increased the absorption of fructose and L-serine in HT-29-D4 cells. Moreover, the mycotoxin did not inhibit the cAMP-dependent chloride secretion through the cystic fibrosis transmembrane conductance regulator channel. The inhibitory effect of OTA on active glucose transport was partially antagonized by L-phenylalanine, but not by alpha-tocopherol, suggesting that the toxicity of OTA could result from an inhibition of protein synthesis, rather than an induction of lipid peroxidation. In particular, OTA affected the protein content of plasma membrane microdomains, which are known to regulate tight junction assembly and intestinal transport activity. Taken together, these data showed that OTA alters both barrier and absorption functions of the intestinal epithelium.

Caco-2 Cells↗
PubMed2006

Oxygen supplementation during airway instrumentation improves intestinal barrier dysfunction.

BACKGROUND/PURPOSE: The study investigates the effect of airway instrumentation on the histopathology of the intestine, contribution of bacterial translocation, and whether oxygen supplementation may counteract the possible detrimental effects of this procedure. METHODS: Fifty-five Wistar rats were assigned to 3 groups. Group 1 served as control. Groups 2 and 3 underwent airway instrumentation. In addition, group 3 received oxygen supplementation during the procedure. Arterial blood gases were measured after the procedure. Samples of mesenteric lymph nodes ileum, cecum, spleen, liver, and blood were harvested for determination of bacterial growth after 24 hours. Ileum was evaluated histologically. RESULTS: In group 2, the rats presented a decrease in oxygen saturation (90% +/- 0.3%, P < .0001), hypoxemia (PaO2, 73 +/- 1.5 mm Hg; P < .0001), and respiratory acidosis (pH 7.27 +/- 0.01; PaCO2, 48 +/- 1.5 mm Hg; P < .0001) after airway instrumentation. These rats also showed evidence of intestinal injury (P < .0001) and bacterial translocation to mesenteric lymph nodes in 10 of 20 rats compared with 0 of 15 in the controls (P = .004). In group 3, oxygen supplementation provided normal arterial blood gas parameters, and led to minimal histologic changes and bacterial translocation in only 1 of 20 rats, compared with group 2 (P < .0001 and P = .005, respectively). CONCLUSIONS: The study suggests that oxygen supplementation during airway instrumentation prevents hypoxemia, intestinal damage, and bacterial translocation.

Animals↗
PubMedDate not supplied

Adhesive mucous gel layer and mucus release as intestinal barrier in rats.

BACKGROUND: Although it has been reported that total parenteral nutrition induces an increased intestinal permeability and a decreased mucous gel layer covering the intestinal epithelium, the role of mucous gel on intestinal permeability has not been well understood. We examined the in vivo effects of N-acetyl cysteine (NAC) as mucolytic agent and colchicine as suppressant of the mucus production on the intestinal transmission of fluorescein isothiocyanate dextran 70,000 (FITC-dextran). METHODS: Rats were divided into four groups. In each group, FITC-dextran (750 mg/kg) with or without NAC (3000 mg/kg) was injected into the small intestinal lumen 3 hours after intraperitoneal injection of saline or colchicine (Col, 10 mg/kg). Thirty minutes after injection of FITC-dextran, blood samples were taken from portal vein to analyze plasma fluorescein concentration by fluorescence spectrometry. Samples of small intestine were sectioned in a cryostat for fluorescence microscopy, and the identical sections were stained by periodic acid-Schiff reaction. RESULTS: Plasma FITC-dextran level in NAC group was higher than that in control group (p < .01), that in Col + NAC group was higher than that in Col group (p < .01) and that in Col + NAC group was higher than that in NAC group (p < .05). The spaces between villi were filled with mucous gel in the control and Col groups, whereas those were not entirely filled with mucous gel in NAC and Col + NAC groups. FITC-dextran and mucous gel showed complementary distribution in all rats. The villous interstitial edema was recognized in NAC group and the villi were disrupted in Col + NAC group. CONCLUSIONS: These results suggest that intestinal permeability is possibly affected not only by the mucous gel covering the intestinal epithelium but also by mucus release from goblet cells of the small intestine.

Acetylcysteine↗
PubMed2006

Dietary fructooligosaccharides affect intestinal barrier function in healthy men.

In contrast to most expectations, we showed previously that dietary fructooligosaccharides (FOS) stimulate intestinal colonization and translocation of invasive Salmonella enteritidis in rats. Even before infection, FOS increased the cytotoxicity of fecal water, mucin excretion, and intestinal permeability. In the present study, we tested whether FOS has these effects in humans. A double-blind, placebo-controlled, crossover study of 2 x 2 wk, with a washout period of 2 wk, was performed with 34 healthy men. Each day, subjects consumed lemonade containing either 20 g FOS or placebo and the intestinal permeability marker chromium EDTA (CrEDTA). On the last 2 d of each supplement period, subjects scored their gastrointestinal complaints on a visual analog scale and collected feces and urine for 24 h. Fecal lactic acid was measured using a colorimetric enzymatic kit. The cytotoxicity of fecal water was determined with an in vitro bioassay, fecal mucins were quantified fluorimetrically, and intestinal permeability was determined by measuring urinary CrEDTA excretion. In agreement with our animal studies, FOS fermentation increased fecal wet weight, bifidobacteria, lactobacilli, and lactic acid. Consumption of FOS increased flatulence and intestinal bloating. In addition, FOS consumption doubled fecal mucin excretion, indicating mucosal irritation. However, FOS did not affect the cytotoxicity of fecal water and intestinal permeability. The FOS-induced increase in mucin excretion in our human study suggests mucosal irritation in humans, but the overall effects are more moderate than those in rats.

Adult↗