Testing treatments expected to cause opposite changes in circulating UA levels should shed light on whether UA is a causal, compensatory or co-incidental factor modifying inflammatory status. In Cohort #1: Uric Acid versus Placebo Trial, UA systemic infusion is expected to rapidly increase circulating UA levels. We expect that the sudden increase of circulating UA levels will directly affect circulating levels of cytokines, antioxidant biomarkers and other outcome parameters. In Cohort #2: Rasburicase versus Placebo Trial, Rasburicase systemic administration is expected to rapidly lower circulating UA levels without restoration within a few days of the infusion. We expect that a sudden decrease in circulating UA levels may affect circulating cytokines, antioxidant biomarkers and all other outcomes in an opposite direction than observed in Cohort #1. These short term single adminsitration studies facilitate better understanding of mechanisms that link elevated circulating UA levels with increased cardiovascular risk suggested by observational and epidemiological data. Additionally, this study explores the effect of sudden changes in cardiovascular risk factors, such as saturated fats or circulating homocysteine concentrations, on biological and instrumental parameters (33, 34). Study Design Twenty participants (5 men and 5 women received UA and 5 men and 5 women received placebo) in Cohort #1 and 20 participants (5 men and 5 women received rasburicase and 5 men and 5 women received placebo in Cohort #2. All participants were evaluated frequently for 24 hours during the active part of the study. The longer-term effects were evaluated at visit 4 and visit 5 performed 48 hours and 2 weeks from treatment, respectively. In all, 40 participants were enrolled and completed all visits. All data have been collected ahd analyses are underway.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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