There is evidence that immune-inflammatory, stress of reactive oxygen and nitrogen species (IO&NS) processes play a role in the neurodegenerative processes observed in Parkinson's disease (PD). The aim of the present study was to investigate peripheral IO&NS biomarkers in PD. We included 56 healthy individuals and 56 PD patients divided in two groups: early PD stage and late PD stage. Plasma lipid hydroperoxides (LOOH), malondialdehyde (MDA), nitric oxide metabolites (NOx), sulfhydryl (SH) groups, catalase (CAT) activity, superoxide dismutase (SOD) activity, paraoxonase (PON)1 activity, total radical trapping antioxidant parameter (TRAP) and C-reactive protein (CRP) were measured. PD is characterized by increased LOOH, MDA and SOD activity and lowered CAT activity. A combination of five O&NS biomarkers highly significantly predicts PD with a sensitivity of 94.5% and a specificity of 86.8% (i.e., MDA, SOD activity, TRAP, SH-groups and CAT activity). The single best biomarker of PD is MDA, while LOOH and SOD activity are significantly associated with late PD stage, but not early PD stage. Antiparkinson drugs did not affect O&NS biomarkers, but levodopa+carbidopa significantly increased CRP. It is suggested that MDA may serve as a disease biomarker, while LOOH and SOD activity are associated with late PD stage characteristic. New treatments for PD should not only target dopamine but also lipid peroxidation.

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Our study indicates a state of systemic inflammation and oxidative stress in PD patients coupled with alterations in Fe metabolism. Chronic inflammation and oxidative pathways in PD may in part determine changes in iron metabolism. New drug treatments for PD should target inflammatory and oxidative stress pathways and iron metabolism as well.

Aims: This study aims to examine the associations between paraoxonase 1 (PON)1 status and acute ischemic stroke (AIS) and consequent disabilities. Methods: This study recruited 122 patients with AIS and 40 healthy controls and assessed the Q192R gene variants, arylesterase (AREase) and chloromethyl phenylacetate (CMPAase) activities, and high-density lipoprotein cholesterol (HDL) in baseline conditions. AREase and CMPAase were measured 3 months later. The National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin score (mRS) were assessed at baseline and 3 and 6 months later. Results: Reduced CMPAase and increased AREase activities are significantly associated with AIS and mRS and NIHSS scores (baseline and 3 and 6 months later). The best predictor of AIS/disabilities was a decrease in the z-unit-based composite zCMPAase-zAREase score. Serum high density lipoprotein cholsterol (HDL) was significantly correlated with CMPAase, but not AREase, activity and a lowered zCMPAase+zHDL score was the second best predictor of AIS/disabilities. Regression analysis showed that 34.7% of the variance in baseline NIHSS was explained by zCMPAase-zAREase and zCMPAase+zHDL composites, HDL, and hypertension. Neural network analysis showed that stroke was differentiated from controls with an area under the ROC curve of 0.975 using both new composite scores, PON1 status, hypertension, dyslipidemia, previous stroke as body mass index. The PON1 Q192R genotype has many significant direct and mediated effects on AIS/disabilities, however, its overall effect was not significant. Discussion: PON1 status and the CMPAase-HDL complex play key roles in AIS and its disabilities at baseline and 3 and 6 months later.

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In acute ischemic stroke (AIS), there are no data on whether lipid and protein oxidation and antioxidant biomarkers are associated with the outcome of AIS above and beyond the effects of traditional risk factors, immune and metabolic biomarkers, and measurements of stroke volume. The present study was conducted in 135 mild to moderate AIS patients and 40 controls and assessed the modified raking scale (mRS) at baseline, and 3 and 6 month later. We measured lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products, paraoxonase 1 (PON1) activities and PON1 Q192R genotypes, high density lipoprotein cholesterol (HDL), sulfhydryl (-SH) groups), and diffusion-weighted imaging (DWI) stroke volume and fluid-attenuated inversion recovery (FLAIR) signal intensity. We found that a) AIS is characterized by lower chloromethyl acetate (CMPA)ase PON1 activity, HDL and -SH groups and increased LOOH and neurotoxicity (a composite of LOOH, inflammatory markers and glycated hemoglobin); b) oxidative and antioxidant biomarkers strongly and independently predict mRS scores 3 and 6 months later and DWI stroke volume and FLAIR signal intensity; c) the PON1 Q192R variant has multiple effects on stroke outcome that are mediated by its effects on antioxidant defenses and lipid peroxidation; and d) the PON1 RR variant has a protective effect against lipid peroxidation, neurotoxicity, infarct volume and stroke outcome. Increased lipid peroxidation and lowered activity of the PON1-HDL complex and -SH groups are drug targets to prevent AIS and consequent neurodegenerative processes with loss of function, and increased levels of oxidative reperfusion mediators due to ischemia-reperfusion injury.

Premature atherosclerosis represents the main cause of mortality among end-stage renal disease patients (ESRD). Increased inflammation and oxidative stress are involved in initiation and progression of the atherosclerotic plaque. As foam cells are capable of producing significant amounts of inflammatory mediators and free radicals, we hypothesized that foam cells from uremic patients could produce more inflammation and oxidative stress than foam cells from normal people and be, somehow, involved in the accelerated atherosclerosis of uremia. To test this hypothesis, the levels of a few markers of inflammation and oxidative stress: Tumor necrosis factor-α, inducible nitric oxide synthase, malondialdehyde, nitric oxide by-products were measured in the supernatants of macrophage-derived foam cells cultures from 18 hemodialysis patients and 18 apparently healthy individuals controls. Malondialdehyde levels in the supernatant of cell cultures (macrophages stimulated or not with native and oxidized lipoprotein) were significantly increased in uremic patients; no statistically significant difference was found between the supernatant concentrations of nitric oxide by-products, inducible nitric oxide synthase activity, and tumor necrosis factor-α between patients and controls. Our results, obtained with human macrophages and macrophage-derived foam cells, are compatible with the theory that increased cellular oxidative stress and inflammatory activity in ESRD patients could accelerate the atherosclerotic process. The present culture protocol showed it is possible to use human mononuclear cells to evaluate the oxidative metabolism of foam cells, which are considered to be the initial step of atherosclerotic lesions.