ABSTRACT
BACKGROUND: Vasoactive intestinal polypeptide (VIP) has been implicated as a regulator of intestinal barrier function and inflammation. Our aim was to elucidate the role of VIP in follicle-associated epithelium (FAE) and villus epithelium (VE) permeability following stress in rats and on human intestinal barrier function. METHODS: Rats were injected intraperitoneally (i.p.) with VIP receptor-antagonists (anti-VPACs), a mast cell stabilizer, doxantrazole (DOX), or NaCl, and submitted to acute water avoidance stress. Ileal segments were mounted in Ussing chambers to assess (51) chromium-edta ((51) Cr-edta) and Escherichia (E.) coli (strain K-12) permeability. Rat ileal and human ileal and colonic segments were exposed to VIP ± anti-VPACs or DOX. An in vitro co-culture model of human FAE was used to study epithelial-VIP effects. VIP/VPACs distribution was assessed by microscopy. KEY RESULTS: Stress increased (51) Cr-edta and E. coli permeability in VE and FAE. The increases were abolished by i.p. injection of DOX or anti-VPACs. Ileal VIP-exposure ex vivo increased bacterial passage and this was reduced by DOX. In human FAE ex vivo, VIP treatment doubled bacterial uptake, which was normalized by DOX or anti-VPACs. No barrier effects were observed in human colonic tissue. VPACs were found in rat and human ileal follicles, with partial mast cell co-localization. The co-culture model confirmed VIP-mast cell-epithelial interactions in the regulation of barrier function. CONCLUSIONS & INFERENCES: Stress affects the FAE barrier by mechanisms involving VIP and VPACs on mucosal mast cells. We suggest a regulatory role for VIP in the control of ileal permeability that may be relevant to bacterial-epithelial interactions in stress-related intestinal disorders.
Subject(s)
Ileum/metabolism , Intestinal Mucosa/metabolism , Mast Cells/metabolism , Stress, Physiological/physiology , Vasoactive Intestinal Peptide/metabolism , Aged , Aged, 80 and over , Animals , Female , Humans , Ileum/drug effects , Intestinal Mucosa/drug effects , Male , Mast Cells/drug effects , Middle Aged , Permeability , Phosphodiesterase Inhibitors/pharmacology , Rats , Rats, Wistar , Receptors, Vasoactive Intestinal Peptide/antagonists & inhibitors , Thioxanthenes/pharmacology , Vasoactive Intestinal Peptide/pharmacology , Xanthones/pharmacologyABSTRACT
BACKGROUND: Patients with collagenous colitis have an impaired mucosal barrier. Moreover, collagenous colitis is associated with bile acid malabsorption. Bile acids can increase bacterial mucosal uptake in humans. Mucosal barrier function was investigated by exposing colonic biopsies to chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA) in Ussing chamber experiments. AIM: To find if low levels of bile acids increase bacterial uptake in colonic biopsies from collagenous colitis patients. METHODS: The study comprised 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease and 10 examined in clinical remission resulting from treatment with 6 mg budesonide); eight healthy individuals undergoing screening colonoscopy served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), potential difference, trans-epithelial resistance and transmucosal passage of Escherichia coli K12 after adding 100 µmol/L CDCA or DCA. RESULTS: When adding 100 µmol/L CDCA or DCA, bacterial uptake increased fourfold in biopsies of patients in remission; CDCA 6.5 units [2.5-9.8] and DCA 6.2 units [2.1-22] (median [IQR]), compared with uptake in biopsies without added bile acids 1.6 units [1.1-3] (P=0.004 and P=0.01 respectively). In active disease and in patients in remission due to budesonide treatment, bile acids did not affect bacterial uptake. Confocal microscopy revealed trans-epithelial passage of E. coli K12 within 30 min. CONCLUSIONS: Low concentrations of dihydroxy-bile acids exacerbate mucosal barrier dysfunction in colonic biopsies of patients with collagenous colitis in remission. This allows a substantially increased bacterial uptake, which may contribute to recurrence of inflammation.
Subject(s)
Bile Acids and Salts/pharmacology , Colitis, Collagenous/metabolism , Colitis, Collagenous/microbiology , Escherichia coli K12/metabolism , Adult , Aged , Aged, 80 and over , Biological Transport , Biopsy , Budesonide/therapeutic use , Case-Control Studies , Chenodeoxycholic Acid/pharmacology , Colitis, Collagenous/pathology , Deoxycholic Acid/pharmacology , Female , Gastrointestinal Agents/administration & dosage , Humans , In Vitro Techniques , Male , Microscopy, Confocal , Middle AgedABSTRACT
We address the problem of the existence and stability of vector spatial solitons formed by two incoherently interacting optical beams in bulk Kerr and saturable media. We identify families of (2+1)-dimensional two-mode self-trapped beams, with and without a topological charge, and describe their properties analytically and numerically.
ABSTRACT
We study, numerically and analytically, linear and nonlinear waveguides induced by optical vortex solitons in a Kerr medium. Both fundamental and first-order guided modes are analyzed, as well as cases of effective defocusing and focusing nonlinearity.
