Linked Life Data

21331560

Source:http://linkedlifedata.com/resource/pubmed/id/21331560

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-3-14
pubmed:abstractText
Altered expressions of the key enzymes in arachidonic acid (AA) metabolism, prostaglandin synthase 1 and 2 and cysteinyl leukotriene C(4) synthase, are of importance in understanding aspirin-induced asthma. We propose a mathematical model of AA metabolism and its interaction with non-steroidal anti-inflammatory drugs (NSAIDs). Model simulations depict the impact of modified expressions of the above enzymes on the time dependent synthesis of cysteinyl leukotrienes and anti-inflammatory prostaglandins before and during NSAID exposure in different model states describing healthy humans as well as aspirin-tolerant and -intolerant asthmatics. The results are compared and evaluated with experimental data taken from the literature. Our results identify the decreased expression of prostaglandin H synthase 1 and increased expression of leukotriene C(4) synthase as the key elements in AA metabolism that contribute to increased leukotriene C(4) and decreased anti-inflammatory prostaglandins after NSAID dosing in aspirin-intolerant patients. On the other hand, the decreased expression of prostaglandin H synthase 2 implies permanently increased leukotriene C(4) and lowers the sensitivity to increased drug doses. The model is used for identification of susceptible patient populations for aspirin and ibuprofen, and for identification of critical aspirin doses that might induce bronchoconstriction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents..., http://linkedlifedata.com/resource/pubmed/chemical/Aspirin, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase, http://linkedlifedata.com/resource/pubmed/chemical/Ibuprofen, http://linkedlifedata.com/resource/pubmed/chemical/Leukotrienes, http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandins F, Synthetic, http://linkedlifedata.com/resource/pubmed/chemical/cysteinyl-leukotriene, http://linkedlifedata.com/resource/pubmed/chemical/leukotriene-C4 synthase, http://linkedlifedata.com/resource/pubmed/chemical/nocloprost
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1573-8744
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
261-78
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Role of expression of prostaglandin synthases 1 and 2 and leukotriene C4 synthase in aspirin-intolerant asthma: a theoretical study.
pubmed:affiliation
Faculty of Natural Sciences and Mathematics, Faculty of Medicine, Faculty of Health Sciences, University of Maribor, Slomškov trg 15, 2000 Maribor, Slovenia. andrej.dobovisek@uni-mb.si
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't