Oxidative stress has been implicated as one of neuronal injury mechanisms associated to a wide variety of neurodegenerative disorders. Increasing attention has focused in the role of free radicals derived from oxygen and nitric oxide in the pathophysiology of HIV-1 dementia. It is well recognized that lipid peroxidation is a prominent manifestation of oxidative stress in the brain. One of the mechanisms by which protein gp 120 exerts its deleterious effect over neurons by enhancing the hydrolysis of arachidonic acid (AA) and its metabolites from macrophages (1). Arachidonic acid inhibits the reuptake of excitatory neurotransmitters like glutamate, resulting in an excessive influx of calcium in the neurons (excitotoxicity). In addition AA can be converted into biologically active compounds such as prostanoids (prostaglandins, prostacyclin, thromboxanes) or leukotrienes, via the cyclo-oxygenase or the lipooxygenase pathway respectively. They mediate the inflammatory response triggered by HIV-1 virus. The isoprostanes, prostaglandin-like compounds, are produced by free radical-catalyzed peroxidation or arachidonic acid independent of cyclo-oxygenase enzyme activity. These compounds appear to be reliable markers of oxidative injury in vivo (2,3). Recent studies have showed elevated levels of F2-isoprostanes in CSF of patients with Alzheimer's disease and Huntington's disease (4,5). However, the measure of isoprostanes levels in plasma and CSF in HIV infected patients has not been studied. The rationale for the proposed study is to determine the F2-isoprostanes levels in plasma and CSF in HIV-1 infected patients, determine how they correlate with CSF viral load and CD 4 levels and examine how F2-isoprostanes levels are affected by anti-retroviral treatment. In addition we will evaluate the association between levels and the cognitive functions of HIV infected patients
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