| dc.contributor |
Anthony Blikslager, Committee Member |
|
| dc.creator |
Wooten, Jenna Gray |
|
| dc.date |
2010-04-02T18:29:45Z |
|
| dc.date |
2010-04-02T18:29:45Z |
|
| dc.date |
2008-12-05 |
|
| dc.date.accessioned |
2023-02-28T17:09:45Z |
|
| dc.date.available |
2023-02-28T17:09:45Z |
|
| dc.identifier |
etd-11072008-104245 |
|
| dc.identifier |
http://www.lib.ncsu.edu/resolver/1840.16/3400 |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/265878 |
|
| dc.description |
ABSTRACT
WOOTEN, JENNA GRAY. The Role of Cyclooxygenase (COX)-2 in the Canine Proximal Gastrointestinal Tract (Under the direction of Drs. Anthony Blikslager and Duncan Lascelles)
In veterinary medicine, NSAIDs are the most commonly prescribed analgesic and anti-inflammatory medications; unfortunately, they are also commonly associated with ulceration and perforation in dogs. Recent studies have indicated that the role of COX-2 appears to be more complicated than originally thought and its inhibition may lead to corresponding benefits or risks. Therefore, we investigated NSAIDs with differing degrees of selectivity and examined the role of COX-2 in the pylorus and duodenum.
Each dog received carprofen (4.4 mg/kg, q 24 h), deracoxib (2 mg/kg, q 24 h), aspirin (10 mg/kg, q 12 h), and placebo (1 dog treat, q 24 h) orally for 3 days (4-week interval between treatments). Prostanoid synthesis was greater in pyloric mucosa than it was in duodenal mucosa. Nonselective NSAIDs significantly decreased prostanoid concentrations in these mucosae, compared with the effects of deracoxib.
Following the same model dogs received deracoxib (2mg/kg q24h PO), firocoxib (5mg/kg q24h PO), meloxicam (Day 1=0.2mg/kg q24h PO, Day 2-3=0.1mg/kg q24h PO), or placebo (1 dog treat, q 24 h). There were no significant effects of varying COX-2 selectivity on gastric and duodenal tissue prostanoid concentrations, and no significant relationship between the degree of selectivity and gross or histological appearance of the mucosa, suggesting that there are no differences among the preferential and selective COX-2 inhibitors with regard to adverse effects on the upper GI tract.
Twenty-seven clinically normal dogs were evaluated to determine if gastrointestinal lesions were present, and to determine if COX-1 and COX-2 expression were different in lesioned tissue compared to normal tissue. Findings show the gross appearance of a dog’s stomach will likely not provide definitive evidence of whether or not disease is present. From our results, COX-2 appears to be upregulated at the sites of inflammation and erosion and so in these situations, non-selective NSAIDs and COX-2 inhibitors could both be problematic, if this elevated COX-2 is actually playing a protective role. It is still not known if there is any difference between the selective COX-2 inhibitors and the non-selective NSAIDs in their ability to inhibit this upregulated COX-2 that is functioning in a protective role. |
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| dc.rights |
I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dis
sertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee.
I hereby grant to NC State University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I
retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
|
| dc.subject |
cyclooxygenase |
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| dc.subject |
gastrointestinal |
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| dc.subject |
canine |
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| dc.subject |
prostaglandins |
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| dc.subject |
NSAIDs |
|
| dc.title |
The Role of Cyclooxygenase (COX)-2 in the Canine Proximal Gastrointestinal Tract |
|