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Title of Journal: Pediatr Surg Int

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Abbravation: Pediatric Surgery International

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Springer Berlin Heidelberg

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DOI

10.1007/bf00190180

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1437-9813

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Blockade of the renin–angiotensin system prevents

Authors: Manabu Okawada Michael W Wilson Scott D Larsen Elke Lipka John Hillfinger Daniel H Teitelbaum
Publish Date: 2016/09/26
Volume: 32, Issue: 12, Pages: 1103-1114
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Abstract

Blockade of the renin–angiotensin system RAS has been shown to alleviate inflammatory processes in the gastrointestinal tract The aim of this study was to determine if blockade of the RAS would be effective in an immunologically relevant colitis model and to compare outcome with an acute colitis modelA losartan analog CCG203025 C23H26ClN3O5S containing a highly polar sulfonic acid moiety that we expected would allow localized mucosal antagonism with minimal systemic absorption was selected as an angiotensin II type 1a receptor antagonist AT1aRA Two colitis models were studied 1 Acute colitis was induced in 8 to 10weekold C57BL/6J mice by 25  dextran sodium sulfate DSS in drinking water for 7 days 2 IL10/colitis Piroxicam 200 ppm was administered orally in feed to 5weekold IL10/mice C57BL/6J background for 14 days followed by enalaprilat ACEI CCG203025 or PBS administered transanally for 14 daysIn the DSS model weight loss and histologic score for CCG203025 were better than with placebo In the IL10/model ACEI suppressed histologic damage better than CCG203025 Both ACEI and CCG203025 reduced proinflammatory cytokines and chemokines

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