[The experience of the functioning of antiepidemic barriers among strategic rocket troops].
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Acute Disease↗
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Results for “Intestinal Barrier Function”
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[An experimental study on the effects of total parenteral nutrition on gut immune barrier function].
In this study, SPF rat models were used. The purpose of the study was to observe the impairment of gut barrier function subsequent to long-term TPN, and evaluate the effect of TPN enriched by alanyl-glutamine (Ala-Gln) on the gut. After 7 day standard TPN, there was a significant decrease of CD3+, CD4+, CD8+ and IgA-containing plasma cells in lamina propria. The percentage of intestinal bacteria coated by S-IgA declined, and bacterial adherence to intestinal epithelial cells increased with an increased incidence of bacterial translocation to mesenteric lymph nodes. All these adverse effects could be attenuated by addition of Ala-Gln to TPN solutions or oral glutamine (Gln) or Ala-Gln administration. The results of the study suggested that long-term standard TPN impaired the immune gut barrier function and therefor facilitated enterogenic infection, and addition of Gln or Ala-Gln significantly benifited gut barrier protection and infection prevention, which might be important to clinical practice.
Animals↗
Adequacy of gut oxygenation in endotoxemia and sepsis.
OBJECTIVE: To provide a succinct overview of current notions regarding sepsis-induced alterations in mesenteric perfusion and oxygen transport. DATA SOURCES: Selected English-language articles dealing with mesenteric perfusion and gut mucosal function during sepsis or endotoxicosis in experimental animals or man. STUDY SELECTION AND DATA EXTRACTION: The review emphasizes findings obtained using a well-characterized porcine model of acute, resuscitated endotoxicosis. Other experimental and clinical studies are discussed as well. DATA SYNTHESIS: Total hepatosplanchnic perfusion and oxygen uptake are increased in most patients with compensated sepsis. No data are currently available from clinical studies regarding the effect of sepsis on mesenteric perfusion per se. Data are unavailable regarding either total hepatosplanchnic or mesenteric blood flow in patients with decompensated sepsis (i.e., septic shock). Therefore, current ideas regarding mesenteric perfusion in sepsis derive primarily from studies using animal models. In a normodynamic porcine endotoxicosis model, mesenteric perfusion and oxygen delivery (DO2) are markedly decreased. The changes in flow and DO2 are accompanied by intestinal mucosal acidosis and increased permeability to hydrophilic solutes, suggesting that these latter phenomena are a consequence of lipopolysaccharide-induced mesenteric hypoperfusion. This idea is supported by the observation that maintenance of normal mesenteric blood flow ameliorates gut mucosal acidosis and hyperpermeability in endotoxic pigs. However, because transmesenteric oxygen consumption is unchanged in endotoxic pigs, the precise mechanistic relationship between hypoperfusion and altered barrier function remains puzzling. CONCLUSION: Mesenteric hypoperfusion may be an important factor leading to alterations in gut epithelial permeability in endotoxicosis and sepsis.
Animals↗
Gastrointestinal transport of macromolecules in the pathogenesis of food allergy.
In this presentation we have reviewed current concepts of antigen (allergen) transport within the gastrointestinal tract. We have shown that luminal antigens must cross the mucosal barrier before attaching to the intestinal microvillus surface. Uptake into the systemic circulation requires pinocytosis and diffusion across the lamina propria into the intravascular space. Several immunologic and non-immunologic defenses help to control and regulate the uptake of intestinal antigens. These include intestinal flora, peristalsis, the gastric barrier, mucus release from goblet cells, hepatic filtration and proteolysis. In many instances, immune complexes, particularly SIgA-specific complexes, stimulate the non-immunologic host defenses to function more effectively. Secretory antibodies therefore act to provide both exclusion of antigens by physical interference with antigen penetration and by augmentation of non-immunologic defenses. Figure 6 depicts the concept of antigen uptake under normal (physiologic) conditions and with altered intestinal host defenses.
Animals↗
The physiological function of drug-transporting P-glycoproteins.
The mammalian drug-transporting or mdr1-type P-glycoproteins can extrude a range of structurally diverse, toxic xenobiotic compounds from cells. Our analysis of knockout mice lacking one or both of the mdr1-type P-glycoproteins indicates that a major function of these proteins is the protection of organisms against many of the toxic xenobiotics to which they can potentially be exposed in nature. P-glycoprotein confers protection by limiting the uptake of compounds from the gastrointestinal tract, and by stimulating excretion of compounds in the liver, kidney, and intestine. Moreover, P-glycoprotein in the blood-brain barrier and other blood-tissue barriers protects sensitive organs from exposure to toxic compounds that may have entered the bloodstream. Although we cannot exclude additional physiological functions for mdr1-type P-glycoproteins, these are not vital, since the mdr1-deficient mice are viable and fertile, and do not display obvious phenotypic abnormalities other than hypersensitivity to drugs.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Purification and characterization of the human epidermal fatty acid-binding protein: localization during epidermal cell differentiation in vivo and in vitro.
Epidermal fatty acid-binding protein (E-FABP) was isolated from human skin and purified to homogeneity. Its molecular mass was estimated to be 15 kDa and the pI of non-denaturing protein was 5.6. Scatchard-plot analysis revealed one class of binding site for oleic acid with a Kd of 0.46 microM. Structure-binding relation experiments revealed a high affinity of E-FABP for stearic acid which decreased on reduction of the number of carbon atoms or introduction of double bonds into the fatty acid chain. Squalene, cholesterol and retinoic acid isomers showed no affinity, suggesting that E-FABP displays high specificity for fatty acids. E-FABP is a scarce cytosolic protein (0.065% of total protein). Only trace amounts could be detected in normal human skin but up to 42.5 +/- 3.4 pmol/mg of protein was found in a non-malignant defect of keratinocyte differentiation (psoriatic lesions). E-FABP levels were low in cultured human keratinocytes grown under proliferation-stimulating conditions but increased about 2-fold on induction of differentiation by Ca2+. Immunohistochemical localization showed cytosolic staining in differentiated cells of normal and psoriatic skin, suggesting a link between E-FABP and keratinocyte differentiation. The presence of E-FABP in tissues other than skin (heart, intestine and adipose tissue) excludes its specific role in fatty acid metabolism in epithelial cells or its involvement in skin lipid-barrier function.
Amino Acid Sequence↗
Bryostatin-1 attenuates TNF-induced epithelial barrier dysfunction: role of novel PKC isozymes.
Tumor necrosis factor (TNF) increases epithelial permeability in many model systems. Protein kinase C (PKC) isozymes regulate epithelial barrier function and alter ligand-receptor interactions. We sought to define the impact of PKC on TNF-induced barrier dysfunction in T84 intestinal epithelia. TNF induced a dose- and time-dependent fall in transepithelial electrical resistance (TER) and an increase in [(3)H]mannitol flux. The TNF-induced fall in TER was not PKC mediated but was prevented by pretreatment with bryostatin-1, a PKC agonist. As demonstrated by a pattern of sensitivity to pharmacological inhibitors of PKC, this epithelial barrier preservation was mediated by novel PKC isozymes. Bryostatin-1 reduced TNF receptor (TNF-R1) surface availability, as demonstrated by radiolabeled TNF binding and cell surface biotinylation assays, and increased TNF-R1 receptor shedding. The pattern of sensitivity to isozyme-selective PKC inhibitors suggested that these effects were mediated by activation of PKC-epsilon. In addition, after bryostatin-1 treatment, PKC-delta and TNF-R1 became associated, as determined by mutual coimmunoprecipitation assay, which has been shown to lead to receptor desensitization in neutrophils. TNF-induced barrier dysfunction occurs independently of PKC, but selective modulation of novel PKC isozymes may regulate TNF-R1 signaling.
Antigens, CD↗
The early increase in intestinal permeability and systemic endotoxin exposure in patients with severe acute pancreatitis is not associated with systemic bacterial translocation: molecular investigation of microbial DNA in the blood.
INTRODUCTION: Sepsis is the main cause of late mortality in patients with severe acute pancreatitis and is largely attributed to secondary infection of pancreatic necrosis with gram-negative enteric organisms. This is commonly preceded by a significant increase in intestinal colonization with such microbes and with early increases in intestinal permeability, thus suggesting a mechanism of bacterial translocation. Whilst cultures of blood specimens from these patients often remain sterile, it is conceivable that bacteria might translocate in small volumes with detrimental effects but elude detection by standard microbial culture techniques. AIMS: To investigate the incidence and frequency with which bacterial DNA may exist in the systemic circulation of patients with acute pancreatitis and to relate that to disease severity, changes in intestinal permeability, and systemic endotoxin exposure. METHODOLOGY: Blood samples were obtained at admission and on days 3 and 7 from 26 patients with acute pancreatitis (seven with severe cases) and from 10 healthy controls for DNA extraction and standard microbial cultures. Polymerase chain reaction techniques were used to amplify a gene region (16S ribosomal RNA) found in all bacteria. Levels of serum endotoxin and antibodies to endotoxin core (EndoCAb) were measured at admission, and intestinal permeability to the macromolecule polyethylene glycol 3350 was determined within 72 hours of the onset of symptoms. RESULTS: Blood cultures yielded and enterococci for one patient with a severe attack and coagulase-negative staphylococci for another patient with a mild attack. No bacterial DNA was found in any of the samples. Endotoxemia was detected in 20 patients (five with severe cases), and levels of serum IgM EndoCAb were depleted in patients with severe attacks but remained relatively unchanged during mild attacks (p = 0.033). Intestinal permeability was significantly increased in patients with severe attacks of acute pancreatitis but remained unchanged during mild attacks (p < 0.05). CONCLUSIONS: Whilst severe attacks of acute pancreatitis are associated with early derangement in gut barrier function and systemic endotoxin translocation, there is no molecular evidence for associated bacterial "translocation."
Acute Disease↗
Reduced postheparin plasma diamine oxidase activity 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 against potentially harmful agents in the gastrointestinal lumen. The functional integrity of the small bowel in patients with chronic renal failure was measured by post-heparin-diaminoxidase (DAO) activity in a low and safe dose of heparin (5000 IU) in patients with chronic renal failure participating in a hemodialysis program. The results of the study provide one of the first observations about a diminished DAO-response in patients with chronic renal failure reflecting a mucosal abnormality in these patients which has to be further characterized. Our findings also show that this reduced DAO activity is not caused by the effect of uremic toxins. These results further show that a smaller and safer i.v. dose of heparin (5000 IU or less) will release DAO activity as reliably as high doses used by others. We therefore conclude that postheparin DAO activity might be used as a new noninvasive test reflecting intestinal function in patients with chronic renal failure.
Adult↗
Neutrophil transepithelial migration and epithelial barrier function in IBD: potential targets for inhibiting neutrophil trafficking.
Neutrophil (PMN) transmigration across mucosal epithelia is a hallmark of inflammatory conditions, such as ulcerative colitis and Crohn's disease. PMN accumulation within epithelial crypts and in the intestinal lumen directly correlates with clinical disease activity and epithelial injury. Currently, the mechanisms by which PMNs migrate across mucosal epithelia are incompletely understood and a better understanding of this process will likely provide new insights into novel treatment strategies for inflammatory bowel disease. In this article, we discuss current advances that define PMN transepithelial migration, specifically focusing on PMN-epithelial adhesive interactions and signaling events. We also describe how these interactions might be specifically targeted for the development of therapeutic strategies to manage mucosal inflammation.
Antigens, CD↗
1997 Harry M. Vars Research Award. Does the route of feeding modify gut barrier function and clinical outcome in patients after major upper gastrointestinal surgery?
BACKGROUND: Direct experimental evidence suggests that total enteral nutrition (TEN) reduces septic morbidity compared with bowel rest and total parenteral nutrition (TPN) and that mucosal support and maintenance of gut barrier function is a key mechanism. This effect is supported indirectly by clinical studies, but this question has not previously been investigated directly in the postoperative patient. This study examined the hypothesis that early enteral feeding after major upper gastrointestinal surgery may modulate gut barrier function and decrease the risk of major infective complications compared with bowel rest and parenteral nutrition. METHODS: A randomized clinical trial of 67 patients (TPN = 34; TEN = 33) fed postoperatively for 7 days was performed. Thirty-day major morbidity and mortality were monitored. Intestinal permeability was measured using the lactulose/mannitol test preoperatively and on postoperative days 1 and 7. Systemic anti-endotoxin core immunoglobulin G and M antibodies and serum albumin and C-reactive protein were quantified at these time points. RESULTS: No clinical benefit was observed in patients fed enterally compared with the parenterally fed group. Intestinal permeability was increased on the 1st postoperative day in association with evidence of endotoxin exposure. By day 7, enteral feeding compared with parenteral feeding had failed to significantly influence any of the gut barrier or systemic parameters. CONCLUSIONS: This randomized controlled trial of TEN vs TPN after major upper gastrointestinal surgery failed to show a clinical benefit for the enteral route. Moreover, enteral nutrition did not modulate gut barrier function postoperatively.
Antibodies↗
Reversal of the effect of albumin on gut barrier function in burn by the inhibition of inducible isoform of nitric oxide synthase.
HYPOTHESIS: The use of albumin in the early resuscitation formula after major burn has been forbidden because of its damaging effect on the gut barrier function. We hypothesize that inhibition of the inducible isoform of nitric oxide synthase to stabilize endothelial permeability and to retain albumin in the vascular space will ameliorate the major trauma-induced gut barrier dysfunction. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: In experiment 1, specific pathogen-free rats undergoing 35% total body surface area burn or sham burn were given equal volumes (7.5 mL/kg) of isotonic sodium chloride solution or albumin from femoral veins for fluid resuscitation at 0, 4, or 8 hours after burn. In experiment 2, intraperitoneal S-methylisothiourea sulfate (7.5 mg/kg) was given immediately after burn to rats from different groups, as in experiment 1 (SMT groups). At 24 hours after burn, the intestinal mucosa was assayed for myeloperoxidase activity as an index for neutrophil sequestration, the distribution of fluorescein isothiocyanate-dextran across the lumen of small intestine was determined to evaluate the intestinal permeability, and bacterial translocation (BT) to the mesenteric lymph nodes (MLNs) and histological findings in the ileum were also examined. RESULTS: Compared with sham burn, burn induced significant increases in intestinal mucosa myeloperoxidase activity, intestinal permeability, BT to the MLNs, and villi sloughing in rats. Albumin administration at 0 or 4 hours after burn enhanced the increases in neutrophil sequestration, permeability, and villi sloughing compared with saline injection at the same times. In contrast, injection of albumin in the burn-SMT group did not aggravate these changes in intestinal myeloperoxidase activity, intestinal permeability, BT to the MLNs, and villi edema. Burn-SMT rats with albumin injections at 4 or 8 hours after burn showed significant 35% and 52% decreases, respectively, in intestinal permeability compared with burn-SMT-saline rats. Use of albumin at 8 hours after burn in combination with S-methylisothiourea significantly attenuated BT to the MLNs and reduced villi edema. CONCLUSIONS: Early albumin resuscitation aggravated the burn-induced gut damage. Albumin administration and inhibition of the inducible isoform of nitric oxide synthase in combination decreased burn-induced gut barrier dysfunction and reversed the damaging effect of albumin on gut barrier function and decreased BT.
Albumins↗
Modulation of gut mucosal biofilms.
Non-digestible inulin-type fructans, such as oligofructose and high-molecular-weight inulin, have been shown to have the ability to alter the intestinal microbiota composition in such a way that members of the microbial community, generally considered as health-promoting, are stimulated. Bifidobacteria and lactobacilli are the most frequently targeted organisms. Less information exists on effects of inulin-type fructans on the composition, metabolism and health-related significance of bacteria at or near the mucosa surface or in the mucus layer forming mucosa-associated biofilms. Using rats inoculated with a human faecal flora as an experimental model we have found that inulin-type fructans in the diet modulated the gut microbiota by stimulation of mucosa-associated bifidobacteria as well as by partial reduction of pathogenic Salmonella enterica subsp. enterica serovar Typhimurium and thereby benefit health. In addition to changes in mucosal biofilms, inulin-type fructans also induced changes in the colonic mucosa stimulating proliferation in the crypts, increasing the release of mucins, and altering the profile of mucin components in the goblet cells and epithelial mucus layer. These results indicate that inulin-type fructans may stabilise the gut mucosal barrier. Dietary supplementation with these prebiotics could offer a new approach to supporting the barrier function of the mucosa.
Animals↗
Evaluation of the gut mucosal barrier: evidence for increased antigen transfer in children with atopic eczema.
BACKGROUND: Intestinal antigen handling determines subsequent immune response to the antigen. Antigens are absorbed across epithelium along two functional pathways. The main pathway is degradative, which reduces the immunogenicity of the antigen. A minor pathway allows the transport of intact proteins, which is crucial for antigen-specific immune responses. The Ussing chamber method allows the quantitative measurement of protein transfer across the intestinal mucosa. OBJECTIVE: This study was designed to explore the theory that altered antigen transfer across the intestinal mucosa is a factor in the pathogenesis of atopic eczema, characterized by hyperactivity to environmental antigens. METHODS: The absorption and degradation of horseradish peroxidase (molecular weight, 40,000 d) were studied in vitro in Ussing chambers. Eighteen biopsy specimens of upper small intestinal mucosa from 14 patients (aged 0.5 to 8 years) with atopic eczema and 18 specimens from 15 age-matched control subjects were examined. RESULTS: The mean (95% confidence interval) absorption of intact horseradish peroxidase was significantly higher in children with atopic eczema than in control subjects: 242 (81-404) pmol . hr(-1) . cm(-2) versus 23 (12-33) pmol . hr(-1) . cm(-2); t = 2.86, p = 0.007. The absorption of degraded horseradish peroxidase was 972 (732-1213) pmol . hr(-1) . cm(-2) in patients with atopic eczema and 672 (532-811) pmol . hr(-1) . cm(-2) in control subjects; t = 2.29, p = 0.03. CONCLUSIONS: Our results may reflect a primarily altered antigen transfer in patients who have atopic eczema, which may initiate and perpetuate prompt immune responses to common environmental antigens, including foods.
Allergens↗
Mucosal immunodeficiency in HIV/SIV infection.
The gastrointestinal tract is one of the major target organs for secondary infections and malignancies in HIV infection in humans indicating disturbed local immunologic defense mechanisms. Immunohistology and flow cytometric studies have demonstrated a more pronounced loss of CD4+ T cells in the intestinal mucosa compared to the peripheral blood in humans infected with HIV. In parallel, activated CD8+ T cells in the lamina propria are increased in this compartment. In SIV-infected nonhuman primates a very early loss of CD4+ T cells in the intestinal mucosa compared to the peripheral blood occurs already at 2 weeks after infection. Depletion and functional impairment of mucosal CD4+ T lymphocytes with consecutive altered cytokine secretion in HIV/SIV infection may explain the breakdown of the mucosal immune barrier leading to secondary opportunistic or nonopportunistic infections and secondary malignancies. In addition, due to the interrelation between the mucosal immune system and epithelium, these changes might be responsible for the partial small intestinal mucosal atrophy and maturational defects in enterocytes observed in HIV-infected patients.
Animals↗
Bacterial translocation in clinical intestinal transplantation.
BACKGROUND: Bacterial translocation (BT) has been suggested to be responsible for the high incidence of infections occurring after small bowel transplantation (SBTx). Bacterial overgrowth, alteration of the mucosal barrier function as a consequence of preservation injury or acute rejection (AR), and potent immunosuppression are all associated with BT. The aim of this study was to evaluate and quantify the correlation of BT with these events. METHODS: Fifty pediatric SBTx recipients on tacrolimus and prednisone immunosuppression were analyzed. Blood, stool, and liver biopsies and peritoneal fluid were cultured (circa 4000 total specimens) when infection was clinically suspected or as part of follow-up. BT episodes were considered when microorganisms were found simultaneously in blood or liver biopsy and stool. RESULTS: BT (average of 2.0 episodes/patient) was evident in 44% of patients and was most frequently caused by Enterococcus, Staphylococcus, Enterobacter, and Klebsiella. The presence of a colon allograft was associated with a higher rate of BT (75% vs. 33.3%). Furthermore, the transplantation procedure (colon vs. no colon) affected the rate of BT: SBTx=40% vs. 25%, combined liver and SBTx=100% vs. 30%, multivisceral transplantation=25% vs. 50%. AR was associated with 39% of BT episodes. BT followed AR in 9.6% of the cases. In 5.2% of the cases, positive blood cultures without stool confirmation of the bacteria were seen. Prolonged cold ischemia time (CIT) affected BT rate significantly (CIT>9 hr 76% vs. CIT<9 hr 20.8%). CONCLUSIONS: This study shows that 1) a substantial percentage of, but not all, BT is associated with AR, 2) the presence of a colon allograft increases the risk for BT, and 3) a long CIT is associated with a high incidence of BT after SBTx.
Acute Disease↗
Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis.
Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg(-1)/day(-1)). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN- supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.
Acute Disease↗
[The barrier-function of the gastrointestinal (author's transl)].
The present review tries to coordinate anatomical barriers and the biochemical and immunological events controlling and even preventing the entry of substances from the external environment into the extra- and intra-cellular space of the body. A selection of diseases with disturbance of the "barrier function" is included.
Biological Transport↗