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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Xanthine oxidase activity and blood glutathione redox ratio in infants and children with septic shock syndrome.

OBJECTIVES: The possible role of xanthine oxidase ( XO) activation in the signal transduction process during the septic shock syndrome was examined. The XO activity index after caffeine intake was assessed simultaneously with the blood glutathione redox ratio, a known parameter of oxidative stress. DESIGN AND SETTING: An investigational clinical study in a nine-bed pediatric intensive care unit. PATIENTS: Critically ill infants and children (n = 34) with systemic inflammatory response syndrome following infection, trauma or major surgery. Biochemical investigations (n = 54) were performed at various stages of the shock syndrome, characterized by pediatric risk of mortality and organ dysmetabolic scores. Controls consisted of 30 healthy children. MEASUREMENTS AND RESULTS: The in vivo XO activity index was measured as the urinary ratio of two metabolites of caffeine: 1-methyluric acid and 1-methylxanthine. The blood concentrations of oxidized (GSSG) and reduced glutathione (GSH) were determined. The XO activity index and redox ratio GSSG/GSH were highly increased in patients in shock dominated by the clinical symptoms of a proinflammatory response. A significantly lower XO activity index was found with an increased GSSG/ GSH in patients whose stage of shock was characteristic of an excessive anti-inflammatory response. The XO activity index and GSSG/ GSH were correlated closely with each other (r = 0.624, n = 54; p < 0.001), and were also related to the daily severity scores. CONCLUSION: Potent and simultaneous activation of the two redox systems strongly indicates a definite role of free radicals from XO in the overspill of the acute proinflammatory reaction of the shock syndrome, followed by a significant downregulation.[1]


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