SEARCH · PubMed Health

Results for “Intestinal Barrier Function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,441 records · Page 80Linked to original sources

PubMed1996

Multiple organ injuries and failures caused by shock and reperfusion after gunshot wounds.

Experiments were performed to observe the changes of multiple system organ failure (MSOF) and gut barrier function caused by shock and reperfusion after gunshot wounds. Eighteen dogs were divided randomly into two groups. In the experimental group, the dogs were subjected to 60 minutes of shock (40mm Hg), followed by reinfusion of shed blood after hindlimb gunshot wounds. In the control group, the dogs experienced pure gunshot wounds without shock and reperfusion. The results showed that dogs in the experimental group developed multiple system organ injuries or failures compared with the control group. The levels of malondialdehyde (MDA) values in plasma were significantly elevated in the experimental group when compared with preinjury and the control group. Gut flora disorder, bacillus intestinalis overgrowth, and bacterial translocation occurred in the experimental group. The pathological results support the gut barrier function injury. The results indicated that pure gunshot wounds do not easily injure gut barrier function and produce MSOF. Gunshot wounds with shock and reperfusion are capable of causing gut flora disorder, bacillus intestinalis overgrowth, and lead to bacterial translocation, furthermore causing MSOF. Although fluid resuscitation is a potential treatment modality, pathogenically, it can lead to MSOF.

Animals↗

PubMed2002

Strain-dependent induction of enterocyte apoptosis by Giardia lamblia disrupts epithelial barrier function in a caspase-3-dependent manner.

We recently demonstrated that Giardia lamblia rearranges cytoskeletal proteins and reduces transepithelial electrical resistance. The effect of G. lamblia on enterocyte apoptosis is unknown, and a possible link between microbially induced enterocyte apoptosis and altered epithelial permeability has yet to be established. The aim of this study was to assess whether G. lamblia induces enterocyte apoptosis in duodenal epithelial monolayers and whether this effect increases epithelial permeability. Monolayers of nontransformed human duodenal epithelial cells were incubated with sonicated or live G. lamblia trophozoites (NF, S2, WB, or PB strains) for 8, 24, and 48 h. Cell cultures were assessed for apoptosis by Hoechst fluorescence staining, enzyme-linked immunosorbent assay for apoptotic nucleosomes, and electron microscopy. In separate experiments, monolayers were pretreated with or without 120 microM caspase-3 inhibitor (Z-DEVD-FMK) for 1 h and were assessed for production of apoptotic nucleosomes, tight junctional integrity (with fluorescent ZO-1 staining followed by confocal laser microscopy), and transepithelial permeability for fluorescein isothiocyanate-dextran. G. lamblia strains NF and S2, but not strains WB or PB, induced enterocyte apoptosis within the monolayers, and this effect was inhibited by Z-DEVD-FMK pretreatment. Using the G. lamblia NF isolate, additional experiments investigated the possible link between enterocyte apoptosis and altered epithelial permeability. G. lamblia NF disrupted tight junctional ZO-1 and increased epithelial permeability, but these effects were also prevented by pretreatment with the caspase-3 inhibitor. These findings indicate that strain-dependent induction of enterocyte apoptosis may contribute to the pathogenesis of giardiasis. This effect is responsible for a loss of epithelial barrier function by disrupting tight junctional ZO-1 and increasing permeability in a caspase-3-dependent manner.

Animals↗

PubMed1996

HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: in vitro-in vivo correlation with permeability data from rats and humans.

The diverse secretory and absorptive functions of the intestinal epithelium are conducted by a mixed population of absorptive cells and mucus-producing goblet cells as the major cell types. In order to approach the main characteristics in an in vitro model, a coculture system of absorptive Caco-2 cells and mucus-secreting HT29-MTX cells was developed and the permeability of a range of different drugs was tested. Variable goblet cell frequency can be achieved, preserving a significant barrier to drug transport and maintaining the differentiated features of both cell types. Absorption rates for actively transported drugs are rather underestimated in the cell culture model when compared to in vivo data. However, a good correlation with fraction absorbed in humans was attained separating the range of passively transported drugs into two groups of well-absorbable compounds with Peff > or = 10 x 10(-6) cm/s and drugs that are absorbed 40-70% with Peff = 0.1-1 x 10(-5) cm/s. A permeability of Peff < 0.1 x 10(-5) cm/s is suggested for low absorbable drugs.

Animals↗

PubMed1997

Long-term function of experimental substitutes of the ileocecal valve.

The bacteriological barrier function of the ileocecal valve (ICV) can be replaced according to the principle of the nipple-valve anastomosis. Since late complications due to technical measures for stabilizing the ileal nipple have been hitherto unknown, 12 adult beagle dogs were operated on by three technical modifications of a nipple-valve anastomosis and were followed up for 1 year: In three cases the ileal nipple was stabilized by longitudinal staples (NVA), in three cases an intestinal neosphincter (INS) was produced by healing of the muscular layers between the ileal nipple and colon, and in six cases an oral zone of stabilization, preserving an aboral valve zone (S-NVA) was constructed. Measures for valve function at the end of the study period were the weight course of the animals and the intestinal bacterial profile, considering morphological complications of the substituted valves. As reference the respective bacterial counts in ICV and end-to-end anastomosis (EEA) were used, which had been determined in the same animals in earlier experiments. Following an initial increase in weight the 3 animals with NVA and the three animals with INS continuously lost weight from the 4th postoperative month onward. The 6 animals with S-NVA, however, showed from the 4th postoperative month onward a significantly higher weight level (p < 0.05), which remained constant up to the end of the 1-year observation period. Because of a morphologically intact structure of the substituted valve a significantly (p < 0.05) better bacteriological clearance of the ileum was confirmed in these animals after 12 months when compared with the EEA group. In contrast, in the NVA and INS animals a severe bacterial overgrowth of the entire small intestine was observed. This was caused by an intestinal stagnation due to partial prolapse of the nipple in NVA and due to fibrotic stenosis in INS. The results of our study suggest that technical measures to relieve the tendency to devaginate are only successful, if they do not lead to obstruction of the orthograde intestinal passage in the long term. Thus, only the clinical introduction of the S-NVA model may be justified.

Animals↗

PubMed2006

Does pharmaconutrition with L-arginine and/or alpha-tocopherol improve the gut barrier in bile duct ligated rats?

BACKGROUND/AIM: Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and alpha-tocopherol supplementation in bile duct ligated rats. METHODS: Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administered alpha-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) alpha-tocopherol. Nitric oxide, malondialdehyde, and alpha-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. RESULTS: The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood alpha-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. CONCLUSIONS: An obvious effect of alpha-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or alpha-tocopherol supplementation did not seem to improve the gut barrier in our model.

Administration, Oral↗

PubMed2004

Role of p38 mitogen-activated protein kinase pathway on renal failure in the infant rat after burn injury.

The p38 mitogen-activated protein kinase (MAPK) pathway is a proinflammatory signal transduction pathway for the production of cytokines and cellular response to stress, such as bacterial LPS or ischemia. We examined the effects of FR167653, a specific inhibitor of p38 MAPK, to explore the relationship between intestinal barrier damage and remote renal dysfunction. Immunohistochemical data showed the accumulation of neutrophils in the intestine after burn, and a horseradish peroxidase (HRP) tracer experiment showed burn-induced intestinal barrier damage. Our quantitative bacterial culture data demonstrated that viable bacteria reached the remote organs after burn and prevented the invading viable bacteria from using FR167653. Western blotting identified increased phosphorylation of p38 MAPK in the kidney after burn, and it may also have shown the possibility that endotoxin associated with the bacterial translocation enhances the activation of the p38 MAPK pathway. We blocked the intestinal barrier damage using FR167653, which resulted in reduced neutrophils in the intestine. FR167653 also prevented the increased phosphorylation of p38 MAPK in the kidney, which resulted in reduced neutrophils in the glomerulus and the reduction of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta mRNA in the kidneys, and, finally, prevented burn-induced renal failure. This study provides evidence for the hypothesis that the p38 MAPK pathway controls inflammatory mediators and not only improves intestinal function but also reduces remote renal failure after burn. We identified the pathophysiologic role of the p38 MAPK pathway in the development of renal failure after burn.

Animals↗

PubMed1991

Care of the gut in the surgical intensive care unit: fact or fashion?

The traditional approach to the care of the gastrointestinal tract in the intensive care unit has been one of neglect. However, recent evidence has linked enteric flora to the generation of clinical sepsis in the absence of other infectious foci. The role of the bowel as an efficient barrier to the invasion of its own flora is addressed in this paper. A variety of insults disrupt the integrity of the barrier function of the gut, allowing the entry of bowel organisms or endotoxins, or both, into the portal and systemic circulatory systems. In animal and early clinical studies, a number of interventions, aimed at altering the enteric flora and enhancing the bowel's barrier function, have been shown to modulate the host's resistance to different insults and may even improve clinical outcome. Such interventions include maintenance of enteral feeding, glutamine supplementation of hyperalimentation solutions and selective bacterial decontamination of the bowel.

Animals↗

PubMed2001

Characterization of Vibrio cholerae O1 El tor galU and galE mutants: influence on lipopolysaccharide structure, colonization, and biofilm formation.

Recently we described the isolation of spontaneous bacteriophage K139-resistant Vibrio cholerae O1 El Tor mutants. In this study, we identified phage-resistant isolates with intact O antigen but altered core oligosaccharide which were also affected in galactose catabolism; this strains have mutations in the galU gene. We inactivated another gal gene, galE, and the mutant was also found to be defective in the catabolism of exogenous galactose but synthesized an apparently normal lipopolysaccharide (LPS). Both gal mutants as well as a rough LPS (R-LPS) mutant were investigated for the ability to colonize the mouse small intestine. The galU and R-LPS mutants, but not the galE mutant, were defective in colonization, a phenotype also associated with O-antigen-negative mutants. By investigating several parameters in vitro, we could show that galU and R-LPS mutants were more sensitive to short-chain organic acids, cationic antimicrobial peptides, the complement system, and bile salts as well as other hydrophobic agents, indicating that their outer membrane no longer provides an effective barrier function. O-antigen-negative strains were found to be sensitive to complement and cationic peptides, but they displayed significant resistance to bile salts and short-chain organic acids. Furthermore, we found that galU and galE are essential for the formation of a biofilm in a spontaneous phage-resistant rugose variant, suggesting that the synthesis of UDP-galactose via UDP-glucose is necessary for biosynthesis of the exopolysaccharide. In addition, we provide evidence that the production of exopolysaccharide limits the access of phage K139 to its receptor, the O antigen. In conclusion, our results indicate involvement of galU in V. cholerae virulence, correlated with the observed change in LPS structure, and a role for galU and galE in environmental survival of V. cholerae.

Animals↗

PubMed2005

Probiotics and prebiotics: role in clinical disease states.

Parents of pediatric patients are seeking alternatives to conventional therapy in the prevention and treatment of gastrointestinal disease states because of therapeutic failures caused by the increased incidence of antibiotic resistance. One such alternative is the use of probiotics and prebiotics to stimulate health-promoting indigenous flora to affect pathogen colonization and expression of disease. Probiotics are live flora given in oral quantities that allow for colonization of the colon. Probiotics are given as functional foods or dietary supplements, and function to activate the mucosal immune system and prevent pathogen colonization and translocation by strengthening the mucosal barrier, interfering with pathogen colonization, and in some instances, producing secretory antibacterial substances. Prebiotics are nondigestible carbohydrates, principally oligosoccharides, that are fermented by colonic commensals, stimulating their proliferation and producing short-chain fatty acids. Both protective nutrients have been shown to reduce the incidence and severity of infantile diarrhea, particularly rotaviral gastroenteritis, prevent antibiotic-induced diarrhea, and prevent and treat intestinal food allergy. With additional multicenter clinical trial confirmations, these substances may become routine in the care of infants and young children.

Child↗

PubMed1996

The trefoil peptide family.

The unique three-loop structure of the trefoil motif, formed by intrachain disulfide bonds in a 1-5, 2-4, 3-6 configuration between six conserved cysteine residues, is the defining feature of a recently recognized family of peptides. Expression of trefoil peptides is closely related to that of mucin glycoproteins in diverse biological sources. Three distinct members of the family (pS2, intestinal trefoil factor, and spasmolytic polypeptide) are produced in the mammalian gastrointestinal tract by mucus-secreting cells and targeted primarily for luminal secretion. The compact structure of the trefoil motif may be responsible for marked resistance of trefoil peptides to proteolytic digestion, enabling them to function in the harsh environment of the gastrointestinal lumen. Trefoil peptides are ectopically expressed adjacent to areas of inflammation within the gastrointestinal tract and may play an important role in both maintaining the barrier function of mucosal surfaces and facilitating healing after injury.

Amino Acid Sequence↗

PubMed1983

Stable, highly immunogenic mutants of "Salmonella" with two independent, attenuating markers as potential live vaccine and their validity for "Shigella" and other bacteria.

This paper presents for Salmonella sp. an easily realizable principle to develop high-immunogenic, stable live vaccines with two independent attenuating mutations, which is valid for Shigella sp. and Pasteurella s. too. To avoid overattenuation by the stepwise introduction of two attenuating markers, only those mutations are suitable which do not suppress pathogenic structures or essential metabolic functions, but only transduce them into a leaky function, as e.g.: mutagen induced auxotrophic phenotypes with diminished virulence by commutation; purine dependent strains, which hitherto erroneously were regarded as non-immunogenic and particularly distinct chromosomal resistant genotypes, in which the conformational change of the drug target simultaneously causes resistance and changes virulence behaviour (pathwaydrift-mutants). Moreover, in Salmonella, an additional high sensitivity marker against ten sides and drugs possessing a permeation barrier in the outer membrane diminishes--without influence on virulence and immunogenicity--surviving in intestine (bile) and (detergent contaminated) environment. Therefore this hst-marker confers antiepidemic quality to vaccine strains and increases safety. To meet security demands for such vaccines with laboratory methods some easy and practicable tests for standardization are suggested, which include estimation of reversion frequency of pur- and hst marker and the proof of immunogenicity for mice. The safety and efficacy of such vaccine strains are pointed out by veterinarians in live-stock.

Animals↗

PubMed2002

Increased proliferation and apoptosis of colonic epithelial cells in dextran sulfate sodium-induced colitis in rats.

We have evaluated morphologic alterations and epithelial cell apoptosis and proliferation of colonic mucosa in the acute and chronic phases of DSS-induced colitis. Colitis was induced in Sprague-Dawley rats by 7 days of 4% DSS oral administration followed by 7 days of tap water for one, two, and three cycles. Control rats receved tap water only. Morphological changes in colonic mucosa were evaluated and scored by light and scanning electron microscopy. Apoptosis was studied by TUNEL assay and cell proliferation by Ki-67 immunoreaction. The expression of both proapoptotic (Fas, FasL, Bax, p53) and antiapoptotic (Bc12) cellular proteins was determined by immunohistochemistry. Morphologic assessment showed the most severe colonic epithelial lesions and inflammation in the distal colon with a trend to increasing severity from the first to the third DSS cycle. In DSS rats, the epithelial apoptotic index increased 20-fold after the first cycle and 120-fold after the second and third cycles compared with the controls; in the same way, the expression index of proapoptotic proteins (Fas, FasL, Bax, p53) dramatically increased. The proliferative index increased about 40 to 60-fold compared to controls, with no difference among the three DSS cycles. In conclusion, DSS-induced colitis in rats, which has many structural and ultrastructural features similar to those seen in human ulcerative colitis, is a suitable model for studying increased epithelial apoptosis and proliferation. Further studies employing this model will permitt two hypotheses to be tested. (1) Increased apoptosis may lead to a breakdown of the epithelial barrier function and facilitate the mucosal invasion of intraluminal microorganisms and/or antigens. (2) Abnormal and persistent epithelial hyperproliferation could be causally related to the development of colorectal cancers in the setting of chronic colonic inflammation.

Animals↗

PubMed2003

Quantitative evaluation of the function of small intestinal P-glycoprotein: comparative studies between in situ and in vitro.

PURPOSE: The extent of intestinal absorption of MDR1 P-glycoprotein (P-gp) substrate drugs may be affected by interindividual differences in the expression level of P-gp, and/or by simultaneously administered P-gp substrates/inhibitors. The purpose of the present study is to examine whether the extent to which the intestinal absorption is affected by P-gp can be predicted from in vitro experiments. METHODS: The in situ intestinal perfusion experiments were performed for 12 compounds in mdrla/lb (-/-) and normal mice to determine the permeability-surface area (PS) product. Thus determined intestinal P-gp function was compared with the in vitro P-gp function, which was determined by comparing the transcellular transport across human P-gp expressing and parental LLC-PK1 monolayers. RESULTS: In situ experimental results revealed that the extent to which the intestinal absorption is affected by P-gp was in the following order: quinidine > ritonavir > loperamide, verapamil, daunomycin > digoxin, cyclosporin A > dexamethasone, and vinblastine. A significant correlation was observed between P-gp function determined in the intestinal perfusion and that in LLC-PKI monolayers. CONCLUSION: The in vitro transcellular transport across P-gp expressing monolayers may be used to predict the extent to which the intestinal absorption is affected by P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

ZO-1 maintains its spatial distribution but dissociates from junctional fibrils during tight junction regulation.

Tight junctions restrict diffusion of hydrophilic solutes through the paracellular pathways of columnar epithelia. It is now apparent that the barrier function of tight junctions is physiologically regulated. Current models of the tight junction envisage junctional subunits consisting of extracellular "kisses" between plasma membranes of adjacent cells, intramembrane components represented by freeze-fracture fibrils, and cytoplasmic elements of the cytoskeleton. Insights into functional relationships between these various components of tight junctions should be provided by mapping component interrelationships in states of altered junctional permeability. Here we define the spatial distribution of ZO-1 during a state of physiological regulation of intestinal absorptive cell tight junctions. Enhanced permeation of absorptive cell junctions in response to activation of apical membrane Na(+)-solute cotransporters does not lead to redistribution of the ZO-1 pool, as judged from quantitative ultrastructural immunolocalization studies employing two different ZO-1 antibodies. Surprisingly, ZO-1, which normally localizes under junctional kisses/fibrils, focally persists at sites where junctional kisses/fibrils are cleared. These findings suggest that 1) spatial redistribution of ZO-1 does not contribute to physiological regulation of junctions elicited by activation of Na(+)-solute cotransport and 2) ZO-1 and junctional fibrils may spatially dissociate during such regulated states.

Animals↗

PubMed1989

Autoradiographic distribution in rat tissues of binding sites for endothelin: a neuropeptide?

Endothelin (ET) is a potent and long-acting vasoconstrictor peptide consisting of 21 amino acids and recently isolated from a medium of cultured porcine endothelial cells. To determine the possible sites of ET action, we have conducted autoradiography and receptor binding assays with 125I-labeled ET in rat tissues. The displaceable binding sites of the ligand were widely distributed, not only in the arteries and heart but also in various other organs, e.g., brain, kidney, lung, adrenal gland, and intestine. The systemically injected ET did not cross the blood-brain barrier, whereas the ligand, applied in vitro, was mainly located in the hypothalamic and thalamic areas, lateral ventricular region, subfornical organ, globus pallidus, and caudate putamen. Both membrane preparations from the brain stem including diencephalon and from the heart ventricle had similar, specific, and high-affinity binding sites for 125I-ET. We suggest that ET is involved in the regulation of a large variety of organ functions and may also act as a neuropeptide.

Animals↗

PubMed2006

Transcytosis of IgE-antigen complexes by CD23a in human intestinal epithelial cells and its role in food allergy.

BACKGROUND & AIMS: Secreted immunoglobulins play an integral role in host defense at mucosal surfaces, and recent evidence shows that IgG can participate in antigen sampling from the intestinal lumen. We examined whether IgE also could facilitate transepithelial antigen sampling. METHODS: Stool samples from food-allergic patients undergoing oral food challenge were analyzed for CD23 and food-specific IgE. CD23 isoform expression on primary human intestinal epithelial cells (IEC) was analyzed by polymerase chain reaction. The role of CD23 isoforms in transcytosis of antigen and IgE-antigen complexes was assessed using polarized human T84 cells retrovirally transfected with CD23a or CD23b. RESULTS: CD23 was expressed constitutively on IECs, and food-allergic patients had increased levels of soluble CD23 and food-specific IgE in the stool after challenge. CD23a, but not CD23b, was expressed by primary human IECs. We show in transcytosis assays that CD23a, but not CD23b, acts as a bidirectional transporter of IgE. In addition, specific IgE facilitated the uptake of antigen from the apical surface of an epithelial monolayer by diverting antigen from delivery to lysosomes. Finally, delivery of antigen-IgE complexes across the epithelial barrier could induce the degranulation of rat basophil leukemia cells transfected with the human high-affinity IgE receptor. CONCLUSIONS: These studies show that CD23a is expressed normally on human IECs, and in the presence of IgE can function as an antigen-sampling mechanism capable of activating subepithelial mast cells. IgE may serve as a secretory immunoglobulin that in concert with CD23 participates in food-induced pathophysiology of the gastrointestinal tract.

Adolescent↗

PubMed2001

Defensins -- innate immunity at the epithelial frontier.

Physical barrier function was formerly believed to play the major role in mucosal protection against luminal bacteria. This view has now been challenged by the discovery of specialized molecules that possess antimicrobial activity. More than 100 peptides have been identified so far, and the number is still growing. These peptides are distributed widely and conserved throughout phylogeny. The epithelial expression of antimicrobial peptides is of particular interest as many pathogens adhere to epithelial surfaces and may eventually invade the host. This rapidly acting defence system of innate immunity is already engaged before adoptive immune interactions take place. These antimicrobial peptides consist of constitutive and inducible forms, potentiating this barrier function in terms of an inflammatory response. One important subgroup of antimicrobial peptides is the family of defensins, which are classified as alpha (alpha-) and beta (beta-) defensins. Eight different peptides with varying antimicrobial properties have been identified. They are distributed widely in humans, and organ-specific expression patterns have been observed. Homologous peptides have been found in other mammals, vertebrates, invertebrates, insects and plants. The identification of alpha-defensins and their murine counterparts, cryptdins, in the small intestine prompted intensive research into epithelial antimicrobial defence.

Animals↗

PubMed1988

Immunological functions of the gut--role of the mucosal immune system.

This review summarizes recent information about immune responses in the intestinal mucosa with emphasis on the role of orally-administered antigens from the external environment. The intestinal mucosa provides an extensive surface for potential absorption of pathogenic environmental antigens, such as microbes, chemicals, and food. The intestinal mucosa is densely populated by IgA-producing plasma cells. The humoral immune responses to antigens in the intestinal mucosa are largely of the IgA class in secretory form (sIgA). This sIgA provides an immunological barrier to absorption of antigens on the mucosal epithelium and to penetration into the body. The cell-mediated immune mechanism is also equipped in the mucosal sites. In addition, the mucosal immune response induces hyporesponsiveness of nonmucosal (systemic) immune reactions, and the liver is an integral part of the mucosal immune system. Thus we consider that the mucosal immune system plays a central role in the maintenance of the homeostasis of the total immune system.

Animals↗