| Protective effects of nonionic tri-block copolymers on bile acid-mediated epithelial barrier disruption. | |
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MedLine Citation:
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PMID: 21937955 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Translocation of bacteria and other luminal factors from the intestine following surgical injury can be a major driver of critical illness. Bile acids have been shown to play a key role in the loss of intestinal epithelial barrier function during states of host stress. Experiments to study the ability of nonionic block copolymers to abrogate barrier failure in response to bile acid exposure are described. In vitro experiments were performed with the bile salt sodium deoxycholate (SDC) on Caco-2 enterocyte monolayers using transepithelial electrical resistance (TER) to assay barrier function. A bisphenol-A coupled tri-block polyethylene glycol, PEG 15-20, was shown to prevent SDC-induced barrier failure. ELISA, LDH, and caspase-3 based cell death detection assays demonstrated that bile acid-induced apoptosis and necrosis were prevented with PEG 15-20. Immunofluorescence microscopic visualization of the tight junctional protein zonula occludens-1 (ZO-1) demonstrated that PEG 15-20 prevented significant changes in tight junction organization induced by bile acid exposure. Preliminary TER-based studies examining structure-function correlates of polymer protection against bile acid damage were performed with a small library of polyethylene glycol-based copolymers. Polymer properties associated with optimal protection against bile acid-induced barrier disruption were PEG- based compounds with a molecular weight > 10 kDa and amphiphilicity. The data demonstrate that PEG-based copolymer architecture is an important determinant that confers protection against bile acid injury of intestinal epithelia. |
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Authors:
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Adam Edelstein; David Fink; Mark Musch; Vesta Valuckaite; Olga Zaborina; Simonida Grubjesic; Millicent A Firestone; Jeffrey B Matthews; John C Alverdy |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-7 |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: - ISSN: 1540-0514 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Chicago Pritzker School of Medicine, 924 East 57th Street, Suite 104, Chicago, Illinois, 60637, phone: (773) 702-1939. 2Department of Surgery, University of Chicago, 5841 South Maryland Avenue, MC 5029, Chicago, Illinois, 60637, phone: (773) 702-0881, fax: (773) 702-2140. 3Materials Science Division, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, Illinois 60439, phone: (630) 252-8298. 4University of Chicago Bioengineering Institute for Advanced Surgery and Endoscopy, 5841 South Maryland Avenue, MC 5029, Chicago, Illinois, 60637, phone: (773) 702-0881. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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