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Results for “Intestinal Barrier Function”

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PubMed2003

Ischemic preconditioning reduces intestinal epithelial apoptosis in rats.

Recent experimental studies have described protective effect of ischemic preconditioning (IPC) on ischemia-reperfusion (I/R) injury of the intestine. We hypothesize that to reach a new point of view on the effect of IPC in intestinal barrier function, the relationship between I/R-induced mucosal injury and apoptosis must first be clarified. The present study was undertaken to investigate the role of IPC on intestinal apoptosis and probable contributions of bcl-2 expression to this process. We also investigated the effect of intestinal IPC on ileal malondyaldihyde levels. Forty-four male Wistar rats were randomized into four groups each consisting of 11 rats: sham-operated control, I/R group (30 min of superior mesenteric artery occlusion), IPC-I/R group (10 min of temporary artery occlusion prior before an ischemic insult of 30 min), and IPC alone group (10 min of preconditioning). Twenty-four hours later, ileum samples were obtained. Ileal malondyaldihyde levels were increased in the I/R group (31.9 +/- 18.8 vs. 106.8 +/- 39.8) but not in the IPC alone and IPC-I/R groups (38.1 +/- 13.6 and 44.7 +/- 12.7; P < 0.01). The number of apoptotic cells was significantly lower in IPC-I/R group than that of I/R group, and these findings were further supported by DNA laddering and M30 findings. Diminished bcl-2 expression observed in the ileal specimens of I/R group was prevented by IPC. Our results indicate that IPC may provide a protective effect on ileal epithelium and that this effect is probably the result of a significant increase in the expression of bcl-2 after the insult. The reversal of apoptosis by IPC might help preserving the vitality of intestinal structures that have a critical function, cessation of which often leads to multiorgan dysfunction syndrome.

Animals↗

PubMed2002

Experimental models of small intestinal transplantation in rats: orthotopic versus heterotopic model.

Two kinds of surgical models of small intestinal transplantation (SITx) in rats, namely heterotopic (HIT) and orthotopic transplantion (OIT), have been reviewed. In OIT, the small intestine of the recipient is removed and the transplanted intestine replaces it in continuity. On the other hand, in the HIT model, the small intestinal grafts are rendered dysfunctional without alimentary tract continuity. Histological evidence showed that acute rejection appeared earlier in HIT as compared to OIT. Hyperplasia and hypertrophy of the muscularis externa produced in the chronic rejection process were more pronounced in HIT allografts. The HIT grafts showed severe mucosal atrophy due to the lack of intraluminal trophic factors, because oral feedings can stimulate tropic hormones for mucosal growth, and provide nutrients for enterocytes. Intestinal permeability was consistently higher after HIT than after OIT. The HIT grafts demonstrated less contractility and less response to chemical stimulation than did OIT grafts. The OIT models are advantageous in studies of intraluminal nutrients, and intestinal secretions in these models might modulate the intestinal immune status and possibly delay rejection. The superior intestinal barrier function and the delayed onset of rejection in OIT rats suggest that nutrients and other factors in the succus entericus are important for the maintenance of intestinal graft function.

Animals↗

PubMed1999

Comparison of intestinal function in human immunodeficiency virus-seropositive patients in Kampala and London.

BACKGROUND: White homosexual men with human immunodeficiency virus (HIV) show progressive impairment of intestinal function assessed in terms of intestinal permeability and absorptive capacity. In this study we aimed to determine the effects of heterosexually acquired HIV on small-intestinal function in native Africans, among whom there is a high prevalence of tropical enteropathy. METHODS: Intestinal absorptive capacity (using 3-O-methyl-D-glucose, D-xylose, and L-rhamnose) and permeability (differential 5-h urinary excretion of lactulose/L-rhamnose) were assessed in healthy white (n = 57) and black (n = 14) controls in London, apparently healthy black Africans in Kampala, Uganda (n = 26), HIV-infected patients with (n = 9) and without (n = 30) diarrhoea in Kampala, and 39 white homosexual men with HIV in London who were stratified to resemble the African patient group. RESULTS: Intestinal integrity and absorptive capacity were significantly (P < 0.01) impaired in both black controls in London and apparently healthy black Africans, compared with white controls. HIV-infected white and black patients without diarrhoea did not differ significantly from white and black African controls, respectively, with the exception of increased intestinal permeability among the white patients. White and black African patients with HIV/acquired immunodeficiency syndrome (AIDS) and diarrhoea were found to have marked malabsorption and increased intestinal permeability. Although the relative increase in intestinal permeability was similar in the two groups, by far the largest values for intestinal permeability were found among black Africans with HIV/AIDS and diarrhoea. CONCLUSIONS: Whites and blacks differ with regard to intestinal barrier function. HIV-positive black Africans without gastrointestinal symptoms differ insignificantly from white Londoners with homosexually acquired disease, whereas those with gastrointestinal symptoms have markedly abnormal indices of small-intestinal function with severely comprised intestinal integrity.

Acquired Immunodeficiency Syndrome↗

PubMed2000

[The significance of the expression of the HSP70 and HSP90 in the intestinal mucosa in scalded rats during early postburn stage].

OBJECTIVE: To investigate the changes in the expression, the tissue contents and the distribution of heat shock protein (HSP) 70 and HSP90 in the intestinal mucosa in scalded rats during early postburn stage and to elucidate the effects of heat shock response of intestinal mucosal cell on burn victim's systemic pathophysiology. METHODS: The scalded rats were taken as the model. ELISA, immunoblotting analysis and immunohistochemical methods were employed to analyze and study the expression, the tissue contents and the distribution and their functional status of HSP70 and HSP90 in the intestinal mucosa. RESULTS: (1) The free HSP70 content in the intestinal mucosa exhibited significantly transient decrease in the early postburn stage. (2) The total contents of HSP70 and HSP90 in the intestinal mucosa increased obviously postburn. (3) There exhibited remarkable heterogeneity of the molecular structure of HSP70 in the intestinal mucosa in the early postburn stage. CONCLUSION: The expression and the changes in the contents and the tissue distribution of the two HSPs in the intestinal mucosal cell might play important roles in the cellular stress reaction of the intestinal mucosa and even in the intestinal barrier functional mechanism.

Animals↗

PubMed1992

Effect of aging and caloric restriction on intestinal permeability.

Intestinal permeability is increased in several disorders such as Crohn's disease or rheumatoid arthritis. Since aging leads to alteration of many biological functions, the effect of aging on intestinal permeability was studied by measuring the intestinal permeability in aging rats gavaged with different size permeability probes--mannitol, polyethylene glycol (PEG) 400, and inulin. In rats fed with control diet, there was a significant increase in intestinal permeability to medium size probes PEG 400 (14.8 +/- 0.4 and 21.0 +/- 1.1% at 3 and 28 months respectively, p less than .01) and mannitol (3.41 +/- 0.4 and 5.3 +/- 0.5% at 3 and 28 months, respectively, p less than .01). Intestinal permeability of the large macromolecule inulin did not change (0.42 +/- 0.03 and 0.38 +/- 0.02% at 3 and 28 months, respectively) with aging. There was no correlation between weight of the rats and their intestinal permeability. Because dietary caloric restriction has been found to prolong the life span, retard deterioration of several biological functions, and affect intestinal absorptive functions, we examined the effect of lifelong calorie restriction on intestinal permeability changes. Lifelong calorie-restricted diet did not affect age-related change in intestinal permeability. We conclude that intestinal permeability of medium size probes increases with aging and that lifelong caloric restriction does not prevent this change. We speculate that age-associated deterioration in intestinal barrier functions could permit increased systemic absorption of lumenal antigens and could perhaps contribute to the genesis of antigen-related age-associated diseases.

Aging↗

PubMed2006

Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease.

BACKGROUND: Epithelial barrier function is impaired in Crohn's disease. AIM: To define the underlying cellular mechanisms with special attention to tight junctions. METHODS: Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn's disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction proteins were investigated immunohistochemically by confocal laser scanning microscopy and quantified in immunoblots. Epithelial apoptosis was analysed in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling and 4',6-diamidino-2-phenylindole staining. RESULTS: Patients with active Crohn's disease showed an impaired intestinal barrier function as indicated by a distinct reduction in epithelial resistance. As distribution of conductivity was even, focal epithelial lesions (eg, microerosions) did not contribute to barrier dysfunction. Instead, freeze fracture electron microscopy analysis showed reduced and discontinuous tight junction strands. Occludin and the sealing tight junction proteins claudin 5 and claudin 8 were downregulated and redistributed off the tight junction, whereas the pore-forming tight junctions protein claudin 2 was strongly upregulated, which constitute the molecular basis of tight junction changes. Other claudins were unchanged (claudins 1, 4 and 7) or not detectable in sigmoid colon (claudins 11, 12, 14, 15 and 16). Claudin 2 upregulation was less pronounced in active Crohn's disease compared with active ulcerative colitis and was inducible by tumour necrosis factor alpha. As a second source of impaired barrier function, epithelial apoptosis was distinctly increased in active Crohn's disease (mean (SD) 5.2 (0.5)% v 1.9 (0.2)% in control). By contrast, barrier function, tight junction proteins and apoptosis were unaffected in Crohn's disease in remission. CONCLUSION: Upregulation of pore-forming claudin 2 and downregulation and redistribution of sealing claudins 5 and 8 lead to altered tight junction structure and pronounced barrier dysfunction already in mild to moderately active Crohn's disease.

Adult↗

PubMed1990

Injury-induced inhibition of small intestinal protein and nucleic acid synthesis.

Small intestinal mucosal weight and nutrient absorption are significantly diminished early after cutaneous thermal injuries. Because these intestinal properties are highly dependent on rates of nucleic acid and protein synthesis, in vivo incorporation of thymidine, uridine, and leucine into small intestinal deoxyribonucleic acid, ribonucleic acid, and proteins were measured. Deoxyribonucleic acid synthesis was markedly decreased with the lowest thymidine incorporation in the jejunum (p less than 0.01); these findings were confirmed by autoradiographic identification of radiolabeled nuclei in the intestinal crypts. Protein synthesis was decreased by 6 h postinjury (p less than 0.01) but had returned to normal by 48 h. Consistent with a decreased rate of protein synthesis, ribonucleic acid synthesis was also decreased 18 h postinjury (p less than 0.01). These decreased deoxyribonucleic acid, ribonucleic acid, and protein synthesis rates are not likely a result of ischemia because in other studies of this injury model, intestinal blood flow was not significantly changed by the burn injury. Potentially, factors initiating the acute inflammatory reaction may directly inhibit nucleic acid and protein synthesis and lead to alterations in nutrient absorption and intestinal barrier function after injury.

Animals↗

PubMed2006

[Intestinal permeability and cirrhosis].

Patients with cirrhosis are at increased risk of developing infections due to bacterial translocation. This process depends on three principal factors: bacterial overgrowth, immunodepression, and altered intestinal permeability. Intestinal barrier functions may be disturbed in cirrhosis, related to the toxic effects of alcohol (on mucosa and biological membranes) and portal hypertensive enteropathy. Few studies on the assessment of intestinal permeability in cirrhotic patients are available, and contradictory results may be explained by methodological differences. However, four studies using a differential sugar absorption test (lactulose-mannitol test, a combination of an oligosaccharide and a monosaccharide) showed an increased intestinal permeability in cirrhotic patients. The recurrence of spontaneous bacterial peritonitis can be appreciated only by one similar case history, a low rate of protides in ascites (<10 g/L), bilirubinemia > 55 micromol/L, and thrombocytopenia<98.000/mm3. These results suggest that primary antibiotherapy prophylaxis should be recommended, but this recommendation is limited by the risk of bacterial resistant selection and by the fact that no patient survival benefits was shown. Intestinal permeability could be another predictive factor to justify preventive antibiotherapy; but more studies are needed and methods should be standardized (technique used to measure permeability, patient groups involved).

Humans↗

PubMedDate not supplied

The modulatory role of gut hormones in elemental diet and intravenous total parenteral nutrition-induced bacterial translocation in rats.

We have previously shown that parenteral and certain elemental diets promote bacterial translocation and that this diet-induced bacterial translocation can be prevented by the provision of bulk-forming dietary fiber. The goal of the current study was to test the hypothesis that fiber's protective effect on diet-induced bacterial translocation was mediated by trophic gut hormones. This hypothesis was tested by using bombesin (which stimulates gut hormone release) or the somatostatin analog Sandostatin (which inhibits gut hormone release) to modulate gut hormone release in rats receiving rat food, intravenous total parenteral nutrition, or an elemental diet. Both bombesin and fiber were effective in preventing elemental diet-induced bacterial translocation, whereas octreotide acetate abrogated the protective effect of fiber. Bombesin was also effective in limiting bacterial translocation in parenterally fed rats. Although both enteral (elemental diet) and parenteral diet-induced bacterial translocation were associated with cecal bacterial overgrowth, loss of small-bowel weight, and loss of mucosal protein content, none of these factors seemed to be primarily responsible for bacterial translocation. Because bombesin decreased the incidence of villous injury in the elemental diet-fed rats and decreased the incidence of villous injury and prevented loss of intestinal barrier function to horseradish peroxidase in the parenterally fed rats, it is possible that bombesin exerted its protective effect by limiting mucosal injury and preserving barrier function.

Animals↗

PubMed2000

Nitric oxide and its metabolites mediate ethanol-induced microtubule disruption and intestinal barrier dysfunction.

Loss of gastrointestinal (GI) barrier integrity has been implicated in a wide range of inflammatory illnesses, including alcoholic cirrhosis. Using monolayers of Caco-2 (intestinal) cells as a model, we showed that the ability of ethanol (EtOH) to disrupt intestinal barrier integrity depends on damage to the microtubule (MT) cytoskeleton, especially oxidative injury. One drug that prevented both the MT damage and barrier disruption was L-N(6)-1-iminoethyl-lysine, a selective inhibitor of the inducible form of nitric-oxide synthase (iNOS). Because of this finding and because overproduction of nitric oxide (NO) and generation of peroxynitrite (ONOO(-)) have been proposed to be responsible for mucosal injury in other GI disorders, we sought to determine whether NO overproduction and ONOO(-) formation mediates EtOH-induced MT damage and loss of intestinal barrier function. To this end, Caco-2 monolayers were exposed to EtOH or to authentic ONOO(-) or ONOO(-) generators with or without pretreatment with iNOS inhibitors or antioxidants. We found that EtOH caused 1) iNOS activation, 2) NO overproduction, 3) increases in oxidative stress and superoxide anion production (superoxide dismutase quenchable fluorescence of dichlorofluorescein), 4) nitration and oxidation of tubulin (immunoblotting), 5) decreased levels of stable polymerized tubulin, and 6) increased levels of disassembled tubulin. EtOH also 7) extensively damaged the MT cytoskeleton and 8) disrupted barrier function. Authentic ONOO(-) or ONOO(-) donors had similar effects. Pretreatment with a selective iNOS inhibitor, L-N(6)-1-iminoethyl-lysine, or with antioxidants (ONOO(-) scavengers urate or L-cysteine; superoxide anion scavenger superoxide dismutase) attenuated damage due to EtOH or to ONOO(-) generators. We conclude that EtOH-induced MT damage and intestinal barrier dysfunction require iNOS activation followed by NO overproduction and ONOO(-) formation. These findings provide a rationale for the development of novel therapeutic agents for alcohol-induced GI disorders that inhibit this mechanism.

Antioxidants↗

PubMed2000

Retinol and retinol-binding protein: gut integrity and circulating immunoglobulins.

Vitamin A (retinol) is required to maintain immunity and epithelial turnover and is a key micronutrient needed for combating infection. Vitamin A actions on the immune system are diverse and cannot be accounted for by a single effect or mechanism. The actions of retinol in maintaining gut integrity in humans and immunoglobulin levels in mice was investigated. For 30 children, performance on the lactulose/mannitol test, a test commonly used to assess intestinal barrier function, was inversely correlated (P=.012) with serum retinol concentrations. Thus, children with lower serum retinol, and presumably poorer vitamin A nutritional status, are more likely to have impaired intestinal integrity. Knockout mice that have impairments in plasma retinol transport have circulating immunoglobulin levels that are half those observed in matched wild type mice. No differences were observed in B and T cell populations present in spleen, thymus, and bone marrow.

Animals↗

PubMed2003

Effects of immunonutrition on intestinal mucosal apoptosis, mucosal atrophy, and bacterial translocation in head injured rats.

BACKGROUND: Immunonutrition has been demonstrated to modulate gut function, reduce infectious complications, hospital stay, and ventilator days in the critical patients. AIM OF THE STUDY: We assessed the effect of immunonutrition for the prevention of intestinal mucosal atrophy, apoptosis, and bacterial translocation in head injured rats. METHODS: Thirty five rats were randomised into 5 groups. Following moderate closed head injury, in Group 1; Standard Enteral Nutrition, Group 2; Immunonutrition, Group 3; TPN, Group 4; pe. saline were applied. Group 5 was control group (chow-fed). The rats were sacrificed and segments of the ileum were removed for histologic examination, and samples of tissues taken for microbiologic evaluation. RESULTS: Both intestinal apoptosis and mucosal atrophy were significantly lower in Group 2 and Group 5 (p<0.008). Bacterial translocation was significantly lower in Group 2 than Group 1 (p<0.008). CONCLUSION: The enteral immunonutrition prevents intestinal barrier function in brain injured rats.

Animals↗

PubMed1993

Nutrition and the gut mucosal barrier.

That the gastrointestinal tract performs important immunologic, metabolic, and barrier functions, in addition to nutrient digestion and absorption, has recently become clear, as have the potential deleterious consequences of loss of mucosal barrier function. Because of the potentially important relationship between nutrition and gut barrier function, this area has received increasing clinical and experimental attention over the past several years. Consequently, this review focuses on how nutrition can modulate the integrity of the gut mucosal barrier. Special attention will be given to the biology of normal intestinal barrier function, as well as to studies investigating the role of nutritionally related variables on the gut mucosal barrier.

Animals↗

PubMedDate not supplied

Elemental diet-induced bacterial translocation associated with systemic and intestinal immune suppression.

BACKGROUND: Elemental diets can lead to a loss of intestinal barrier function, promote bacterial translocation, and impair host immune defenses. The purpose of this study was to determine the effects of i.v. and orally administered total parenteral nutrition (TPN) solution on systemic and intestinal immunity and to establish whether supplemental cellulose fiber could improve the impaired immune response. METHODS: The incidence of bacterial translocation and immune function was quantitated by measuring organ weights, immune cell population levels, and the mitogenic response of lymphocytes from the spleen, mesenteric lymph nodes and Peyer's patches of rats receiving parenteral or enteral TPN solution, with and without fiber supplementation. RESULTS: Parenteral and enterally administered TPN solution promoted bacterial translocation to the mesenteric lymph nodes, reduced immune cell population levels, and decreased the lymphocyte mitogenic response to T- and B-cell mitogens. Supplemental cellulose fiber reduced the incidence of diet-induced bacterial translocation from 84% to 31% (p < .01) and improved immune cell function. To more closely examine the relationship between bacterial translocation and impaired lymphocyte mitogenic activity, rats receiving TPN orally or i.v. were separated into two groups based on whether or not bacterial translocation occurred. Rats in which fiber prevented bacterial translocation had normal mitogenic responses, whereas the sub-group of rats in which fiber failed to prevent bacterial translocation had profound decreases in their lymphocyte mitogenic responses. CONCLUSIONS: Both parenteral and enteral elemental diets induced bacterial translocation and impaired systemic and intestinal immune function. Fiber supplementation was effective in reducing elemental diet-induced bacterial translocation and significantly prevented diet-induced impairment of lymphocyte function.

Administration, Oral↗

PubMed2003

Differential alterations in intestinal permeability after trauma-hemorrhage.

BACKGROUND: Recent studies have shown that the intestinal barrier function is altered and macromolecules can translocate after trauma and hemorrhagic shock. The translocated molecules are absorbed from the lymphatic tissue or directly enter the circulation in the gut. However, it remains unknown to what degree these compartments contribute to the clearance of the macromolecules. METHODS: Male Sprague-Dawley rats (350-400 g) underwent a 5-cm midline laparotomy (i.e., soft tissue injury), were bled to a mean arterial pressure of 35 mmHg and maintained for approximately 90 min, and then resuscitated with Ringer's lactate (4x the shed blood volume) over 60 min. At 2 h after resuscitation, a solution containing 51Cr-EDTA, FITC-dextran-4 kDa, and rhodamine B-dextran-40 kDa was instilled into a jejunal blind loop and their concentrations were determined in mesenteric lymph and blood samples harvested between 2 h and 4 h after resuscitation. RESULTS: Trauma-hemorrhage and crystalloid resuscitation significantly increased mesenteric lymph flow and the mucosal permeability for the three marker molecules. There was no difference in the concentrations of 51Cr-EDTA between the blood and lymph compartment after trauma-hemorrhage. However, the high molecular weight marker (rhodamine-B-dextran-40 kDa) accumulated in significantly higher concentrations in the mesenteric lymph than in the plasma under such conditions. CONCLUSIONS: The accumulation of macromolecules in the mesenteric lymph suggests that this compartment plays an important role in the altered gut barrier function after trauma-hemorrhage.

Animals↗

PubMed2004

[The protective effect of supplementation of probiotics combined with riboflavin on the intestinal barrier of the rats after scald injury].

OBJECTIVE: To investigate the effect and its possible mechanism of the supplementation of probiotics combined with riboflavin on the intestinal barriers of the rats after scald injury. METHODS: Seventy Wistar rats were used in the study and were randomly divided into scald control (SC, n = 30), scald and treatment (ST, n = 30) and normal control (NC, n = 10) groups. The rats in SC and ST groups were subjected to 30% TBSA III degree scald. 1.5 ml of isotonic saline suspension containing 5 x 10(12) CFU/L of Bifidobacteria, 5 x 10(10) CFU/L of Bacillus cereus and 5 mg/L of riboflavin was given to rats by gavage in ST group twice a day. For the rats in SC and NC group equal amount of isotonic saline was fed twice a day. The changes in the incidence of bacterial translocation, the amount of intestinal membranous flora, the synthesis and secretion of SIgA in the ileum, and the repair of injured intestinal mucosa were observed. RESULTS: The incidence of bacterial translocation in ST group was significantly lower than that in SC group (P = 0.000 - 0.025). The plasma level of endotoxin in ST group was markedly lower than that in SC group on 3 post-scald day (PSD) (P < 0.05). The amount of bifidobacteria in caecal membrane flora increased by about 20 to 40 fold, whereas the amounts of E. coli and fungi significantly decreased (P < 0.01). The membranous injury scoring was 3 to 0 on 5 PSD (P < 0.05), and the SIgA content in intestinal mucus returned to normal value on the 5th PSD (P < 0.01) in the ST group. CONCLUSION: Supplementation of probiotics together with riboflavin could ameliorate translocation of bacteria and endotoxin in rats with scald injury, implying that the intestinal barrier function was effectively protected.

Animals↗

PubMed1993

Thermal injury-induced changes in the rat intestine brush border cytoskeleton.

BACKGROUND: The brush border cytoskeleton maintains the selective absorptive surface of the intestine epithelium. Increased intestinal permeability caused by cutaneous thermal injury may be the result of changes in the organization of the brush border cytoskeleton. METHODS: In this study we used electron and laser confocal microscopy to examine the temporal and spatial organization of the rat brush border cytoskeleton after thermal injury. RESULTS: Vesiculation of microvilli and disruption of core actin filament bundles were observed in rats with burns covering 20% total body surface area (TBSA). In rats with 40% TBSA burns changes in the brush border cytoskeleton were more pronounced, resulting in increased vesiculation of microvilli and disruption of terminal web actin filaments. Confocal microscopy of corresponding areas of the gut epithelium after staining with rhodamine-phalloidin showed rearrangement of brush border actin filaments. Although tight junctions were intact, the apical region of the gut epithelium in rats with 40% TBSA burns was constricted, possibly because of contraction of brush border actin filaments. Changes in brush border structure and cytoskeletal organization were most pronounced in the ileum of rats 18 hours after injury. CONCLUSIONS: These findings suggest that disruption of the brush border cytoskeleton may, in part, be responsible for the loss of intestinal barrier function after thermal injury in animal models.

Actins↗

PubMed1999

Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis.

BACKGROUND & AIMS: Mechanisms of diarrhea in ulcerative colitis (UC) are still unknown. Functional and structural characterization of epithelial barrier and transport properties in ulcerative colitis (UC) was performed. METHODS: Inflamed sigmoid colon epithelium from UC patients was studied by alternating current impedance analysis to determine the pure epithelial resistance as a measure of intestinal barrier function. Tight junction (TJ) structure was investigated by freeze-fracture electron microscopy. RESULTS: Although total wall resistance was reduced in UC by 50%, impedance analysis uncovered a much more pronounced barrier defect. Epithelial resistance decreased from 95 +/- 5 to 20 +/- 3 omega3. cm2, which in conventional analysis is masked by an increase in subepithelial resistance from 14 +/- 1 to 36 +/- 3 omega3. cm2 caused by inflammation. This was paralleled by a change in epithelial cell TJ structure in UC. Strand count decreased from 6.94 +/- 0.25 to 4.76 +/- 0.47 at the surface and from 7.26 +/- 0.31 to 5.46 +/- 0.37 in the crypts. CONCLUSIONS: The inflamed colonic mucosa in UC has an impaired barrier function that is much more pronounced than previously assumed. An altered TJ structure contributes to this barrier defect which, because of increased back leak, can reduce net ion transport. Thus, a leak-flux mechanism contributes to the diarrhea in UC.

Chloride Channels↗