application): Inflammatory joint diseases represent a major medical problem. Human chronic joint diseases such as arthritis are associated with cells with altered function and regulation. Numerous studies suggest that many of these cellular abnormalities are associated with reactive oxygen species. Both an increase in the production of free radicals and decreased antioxidant defense mechanisms are associated with inflammatory joint disease. At sites of inflammation such as the rheumatoid joint and synovial fluid, increased lipid peroxidation levels have been detected. It is postulated that the arthritic joint is a site of overproduction of free radicals, and that the administration of anti-oxidants will result in beneficial and significant anti-inflammatory activity. Preliminary experimental evidence to support this hypothesis has been generated. These results indicate that certain structural analogs of alpha-phenyl- N-tert-butyl nitrone (PBN) can suppress experimental joint inflammation in a rat model with comparable efficacy to NSAIDs. Due to unique mechanisms of action of these compounds, the are unlikely to possess significant side effects associated with NSAIDs. These findings and associated in vitro findings form the basis of this phase I SBIR grant proposal. The investigators plan to examine if certain proprietary nitrone-related therapeutics will inhibit inflammatory joint disease.
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