Metabolomic profiling to develop blood biomarkers for Parkinson's disease.
ABSTRACT The development of biomarkers for the diagnosis and monitoring disease progression in Parkinson's disease (PD) is of great importance since diagnosis based on clinical parameters has a considerable error rate. In this study, we utilized metabolomic profiling using high performance liquid chromatography coupled with electrochemical coulometric array detection (LCECA) to look for biomarkers in plasma useful for the diagnosis of PD. We examined 25 controls and 66 PD patients. We also measured 8-hydroxy-2-deoxyguanosine (8-OHdG) levels as a marker of oxidative damage to DNA. We initially examined the profiles of unmedicated PD subjects compared to controls to rule out confounding effects of symptomatic medications. We found a complete separation of the two groups. We then determined the variables, which played the greatest role in separating the two groups and applied them to PD subjects taking dopaminergic medications. Using these parameters, we achieved a complete separation of the PD patients from controls. 8-OHdG levels were significantly increased in PD patients, but overlapped controls. Two other markers of oxidative damage were measured in our LCECA profiles. Uric acid was significantly reduced while glutathione was significantly increased in PD patients. These findings show that metabolomic profiling with LCECA coulometric array has great promise for developing biomarkers for both the diagnosis, as well as monitoring disease progression in PD.
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ABSTRACT: The functional reach (FR) test as a complex measure of balance including limits of stability has been proven to differentiate between patients with Parkinson's disease (PD) and controls (CO). Recently, it has been shown that the instrumentation of the FR (iFR) with a wearable sensor may increase this diagnostic accuracy. This cross-sectional study aimed at investigating whether the iFR has the potential to differentiate individuals with high risk for PD (HRPD) from CO, as the delineation of such individuals would allow for, e.g., early neuromodulation. Thirteen PD patients, 13 CO, and 31 HRPD were investigated. HRPD was defined by presence of an enlarged area of hyperechogenicity in the mesencephalon on transcranial sonography and either one motor sign or two risk and prodromal markers of PD. All participants were asked to reach with their right arm forward as far as possible and hold this position for 10 s. During this period, sway parameters were assessed with an accelerometer (Dynaport, McRoberts) worn at the lower back. Extracted parameters that differed significantly between PD patients and CO in our cohort [FR distance (shorter in PD), anterior-posterior and mediolateral acceleration (both lower in PD)] as well as JERK, which has been shown to differentiate HRPD from CO and PD in a previous study, were included in a model, which was then used to differentiate HRPD from CO. The model yielded an area under the curve of 0.77, with a specificity of 85%, and a sensitivity of 74%. These results suggest that the iFR can contribute to an assessment panel focusing on the definition of HRPD individuals.Frontiers in Aging Neuroscience 10/2014; 6:286. DOI:10.3389/fnagi.2014.00286 · 2.84 Impact Factor
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ABSTRACT: Community-acquired pneumonia (CAP) is generally considered a major cause of morbidity and mortality in the elderly. This study aimed to assess the efficacy of adjunctive coenzyme Q10 (CoQ10) in the treatment of elderly CAP. Hospitalized elderly patients with CAP (diagnosed by using defined clinical and radiological criteria) were randomized to receive oral CoQ10 (200 mg/d) or placebo for 14 days, along with antibiotics. Primary and secondary outcomes on days 3, 7, and 14 were measured. Disease severity was scored using CURB-65 index. Statistical analysis was performed using SPSS and P value < 0.05 was considered significant. We enrolled 150 patients for this research. Then, 141 patients, including 70 patients in the trial group and 71 patients in the control group were analyzed. Mean age of the trial and control groups were 67.6 ± 7.2 years and 68.7 ± 7.9 years, respectively. Clinical cure at days 3 and 7 were 24 (34.3%) and 62 (88.6%) in the trial group (P value = 0.6745) and 22 (31%) and 52 (73.2%) in the placebo group (P value = 0.0209). Patients on CoQ10 had faster defervescence (P value = 0.0206) and shorter hospital stay (P value = 0.0144) compared with the placebo group. The subgroup analysis of the patients with severe pneumonia showed differences in clinical cure at day 14. Treatment failure was less in CoQ10 group than in the placebo group (10% versus 22.5% and P value = 0.0440). Adverse events in two groups were few and similar. CoQ10 administration has no serious side effects and can improve outcome in hospitalized elderly CAP; therefore, we recommend it as an adjunctive treatment in elderly patients.