Source:http://linkedlifedata.com/resource/pubmed/id/16373427
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2006-3-15
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pubmed:abstractText |
Traditional NSAIDs, selective cyclooxygenase (COX)-2 inhibitors, and inhibitors of nitric oxide synthase (NOS) impair the healing of preexisting gastric ulcers. However, the role of COX-1 (with or without impairment of COX-2) and the interaction between COX and NOS isoforms during healing are less clear. Thus we investigated healing and regulation of COX and NOS isoforms during ulcer healing in COX-1 and COX-2 deficiency and inhibition mouse models. In this study, female wild-type COX-1(-/-) and COX-2(-/-) mice with gastric ulcers induced by cryoprobe were treated intragastrically with vehicle, selective COX-1 (SC-560), COX-2 (celecoxib, rofecoxib, and valdedoxib), and unselective COX (piroxicam) inhibitors. Ulcer healing parameters, mRNA expression, and activity of COX and NOS were quantified. Gene disruption or inhibition of COX-1 did not impair ulcer healing. In contrast, COX-2 gene disruption and COX-2 inhibitors moderately impaired wound healing. More severe healing impairment was found in dual (SC-560 + rofecoxib) and unselective (piroxicam) COX inhibition and combined COX impairment (in COX-1(-/-) mice with COX-2 inhibition and COX-2(-/-) mice with COX-1 inhibition). In the ulcerated repair tissue, COX-2 mRNA in COX-1(-/-) mice, COX-1 mRNA in COX-2(-/-) mice, and, remarkably, NOS-2 and NOS-3 mRNA in COX-impaired mice were more upregulated than in wild-type mice. This study demonstrates that COX-2 is a key mediator in gastric wound healing. In contrast, COX-1 has no significant role in healing when COX-2 is unimpaired but becomes important when COX-2 is impaired. As counterregulatory mechanisms, mRNA of COX and NOS isoforms were increased during healing in COX-impaired mice.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0193-1857
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
290
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G747-56
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16373427-Animals,
pubmed-meshheading:16373427-Cyclooxygenase 1,
pubmed-meshheading:16373427-Cyclooxygenase 2,
pubmed-meshheading:16373427-Isoenzymes,
pubmed-meshheading:16373427-Mice,
pubmed-meshheading:16373427-Mice, Knockout,
pubmed-meshheading:16373427-Nitric Oxide Synthase,
pubmed-meshheading:16373427-Stomach Ulcer,
pubmed-meshheading:16373427-Wound Healing
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pubmed:year |
2006
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pubmed:articleTitle |
Role of the different isoforms of cyclooxygenase and nitric oxide synthase during gastric ulcer healing in cyclooxygenase-1 and -2 knockout mice.
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pubmed:affiliation |
Department of Clinical Research, University of Berne, Switzerland. adrian.schmassmann@kssw.ch
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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