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- Münch, Andreas, 1970-, et al.
(författare)
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Dihydroxy bile acids increase mucosal permeability and bacterial uptake in human colon biopsies
- 2007
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 42:10, s. 1167-1174
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Bile acids in mM concentrations are known to increase chloride secretion and alter mucosal permeability in animal colon. Increased mucosal permeability is believed to play an important role in the development of intestinal inflammation. The aim of this study was to investigate the influence of μM concentrations of dihydroxy bile acids on permeability and bacterial uptake in the normal human colon. Material and methods. Endoscopic biopsies from the sigmoid colon of 18 subjects with normal colonic histology were mounted in modified Ussing chambers. Chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) were added to the mucosal compartment. Short-circuit current (Isc) and transepithelial resistance (TER) were studied for 120 min. Cr-EDTA and horseradish peroxidase (HRP) were used to assess paracellular and transcellular permeability, respectively. The transmucosal passage of chemically killed Escherichia coli was quantified and investigated using confocal microscopy. Results. A significant decrease in TER was seen after 60 min of exposure to 1000 μmol/l CDCA and DCA. The combination of E. coli and 100 μmol/l CDCA gave a decrease in TER compared to controls (p=0.06). DCA showed a dose-related increase in Cr-EDTA permeability, which was most pronounced at 1000 μmol/l (p=0.02). Increased E. coli uptake was induced by 500 μmol/l (p=0.01) and 1000 μmol/l CDCA (p=0.04). Bacterial uptake was increased at 100 μmol/l by exposure to DCA (p=0.03). Confocal microscopy revealed the presence of E. coli bacteria in the lamina propria after 15 min of exposure to 1000 μmol/l CDCA and DCA. Conclusions. Our study suggests that dihydroxy bile acids in μM concentrations alter barrier function in normal human colon biopsies, causing increased antigen and bacterial uptake, thereby bile acids may contribute to the development of intestinal inflammation. © 2007 Taylor & Francis.
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| 2. |
- Münch, Andreas, 1970-, et al.
(författare)
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Dynamics of mucosal permeability and inflammation in collagenous colitis before, during, and after loop ileostomy
- 2005
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 54:8, s. 1126-1128
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Tidskriftsartikel (refereegranskat)abstract
- Collagenous colitis has become a more frequent diagnosis but the aetiology of this disease is still unknown. We describe a female patient with intractable collagenous colitis who was treated with a temporary loop ileostomy. She was followed clinically, histopathologically, and functionally by measuring mucosal permeability before surgery, after ileostomy, and after bowel reconstruction. In our case report, active collagenous colitis was combined with increased transcellular and paracellular mucosal permeability. Diversion of the faecal stream decreased inflammation of the mucosa and normalised epithelial degeneration and mucosal permeability. After restoration of bowel continuity, mucosal permeability was altered prior to the appearance of a collagenous layer.
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| 3. |
- Munch, Andreas, et al.
(författare)
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Increased Transmucosal Uptake of E-coli K12 in Collagenous Colitis Persists After Budesonide Treatment
- 2009
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 104:3, s. 679-685
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Collagenous colitis is increasingly recognized as a common diarrheal disorder of inflammatory origin. Intestinal inflammation is generally associated with increased mucosal permeability, but little is known about barrier function in microscopic colitis. Our aim was to investigate the mucosal barrier to nonpathogenic bacteria in collagenous colitis. METHODS: The study included 33 individuals, 25 with collagenous colitis (14 in clinical remission, 11 with active disease, and 8 of these again after 6 weeks budesonide treatment) and 8 control patients. Bowel movements were registered for 1 week. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (I-sc), transepithelial resistance (TER), and transmucosal passage of chemically killed Escherichia coli K12. RESULTS: Bacterial uptake was increased in patients in remission, 1.6 U (1.1-3.0) and in those with active disease, 4.6 U (2.5-5.8; median (IQR)), compared to controls, 0.7 U (0.1-1.1; P=0.004 and P=0.001, respectively). Active disease also had significant decrease in transepithelial resistance (TER) after 120 min, -9.7 Omega cm(2) ((-13)-(-4.3)), compared to controls, -5.2 Omega cm(2) ((-7.2)-(-3.1)), P=0.03; or patients in remission, -4.8 Omega cm(2) ((-8.0)-(-1.2)), P=0.04. Budesonide decreased median stool frequency to 1.9 (1.3-2.2) compared to 3.8 (3.7-4.2) before treatment (P=0.01), but bacterial uptake was still increased after budesonide 2.9 U (1.5-3.8), (P=0.006 compared to controls), and there were no significant changes in histology. CONCLUSIONS: Collagenous colitis presents with significantly increased uptake and altered mucosal reactivity to nonpathogenic bacteria. Budesonide induces clinical remission and restores mucosal reactivity but does not abolish the increased bacterial uptake. An underlying barrier dysfunction may explain the frequent and rapid relapses in CC.
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