Pratico's team measured isoprostane, a biomarker for oxidative stress; thromboxane, an index of platelet activation; and prostacyclin, a measure of blood vessel activation in the samples. "This study represents the first observation that the rates of thromboxane and prostacyclin synthesis are both not only significantly increased in autism, but are closely correlated with the rate of oxidative stress," says Pratico. Compared with controls, children with autism had significantly higher urinary levels of isoprostane, thromboxone, and prostacyclin.

Oxidative stress is the result of an excessive formation of chemically unstable byproducts, called free radicals, within the cell. Under normal conditions, the cell is able to destroy the free radicals. However, when excessive free radicals accumulate, these molecules mount an attack against the cell in search of chemical stability.

"During oxidative stress, it is as if the free radicals have only one leg," explains Pratico. "They are searching for the second leg in order to keep from falling. Unfortunately, the ability of the excessive free radicals to reestablish their chemical equilibrium comes always with a price for the organ -- irreversible cellular and organ damage." Free radicals can damage cell membranes, proteins, and genes by oxidation -- the same chemical reaction that causes iron to rust.

Pratico and colleagues measured levels of isoprostane, the chemical byproduct of free radicals attacking fat cells and found that patients with autism possess nearly double the level of oxidative stress than that measured in healthy controls.

The samples from autistic patients also revealed a biochemical imbalance in the patients' blood vessels, resulting in high levels of thromboxane an indicator of platelet ac
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
15-Aug-2006