ABSTRACT
Evidence on the efficacy of high-dose coenzyme Q10 (CoQ10) in Parkinson's disease (PD) is conflicting. An open-label dose-escalation study was performed to examine the effects of CoQ10 on biomarkers of oxidative damage and clinical outcomes in 16 subjects with early idiopathic PD. Each dose (400, 800, 1200, and 2400 mg/day) was consumed daily for 2 weeks. High-dose CoQ10 was well tolerated and improvements in the total Unified Parkinson's Disease Rating Scale (median, 37 vs. 27; p=0.048) were observed following study completion. Plasma F2-isoprostanes (adjusted for arachidonate) were significantly reduced in the 400-1200 mg/day dose range, but increased at 2400 mg/day dosage. A similar pattern of change was observed with serum phospholipase A2 activities. Levels of plasma all trans-retinol, plasma total tocopherol, serum uric acid, and serum total cholesterol were unchanged despite an increase in the CoQ10 dosage. Subjects with symptomatic benefits from CoQ10 (decrease in total UPDRS >10 points) had lower baseline plasma ubiquinol (p=0.07, Mann-Whitney U test) and decreased F2-isoprostanes per unit arachidonate (p=0.04, Wilcoxon Signed-Ranks test). These results lead to the hypothesis that the therapeutic response to CoQ10 depends on baseline levels of ubiquinol and whether the dosage of CoQ10 used can ameliorate the burden of oxidative damage.
Subject(s)
Oxidative Stress/drug effects , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Ubiquinone/analogs & derivatives , Biomarkers, Tumor/blood , Biomarkers, Tumor/metabolism , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Oxidation-Reduction , Treatment Outcome , Ubiquinone/administration & dosage , Ubiquinone/pharmacology , Ubiquinone/therapeutic useABSTRACT
BACKGROUND: We performed a case-control study to assess the relationship between vascular endothelial growth factor (VEGF) and its soluble receptors (sVEGFR-1 and 2) in adult patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). METHODS: We recruited 60 adult patients (34 DF and 26 DHF) with serologically-confirmed dengue infections, 10 patients with non-hemorrhagic infections, and 31 community-based healthy volunteers. The levels of VEGF, sVEGFR-1, and sVEGFR-2 were measured and the differences in these markers were compared using one-way analysis of variance (ANOVA), which was adjusted for multiple comparisons. RESULTS: We observed lower VEGF levels in DF and DHF compared to study controls (p<0.01). sVEGFR-1 was higher in DHF than DF, whilst sVEGFR-2 was lower in DF and DHF compared to study controls (all p<0.01). In DHF, lower VEGF levels were observed in older patients. The use of a single marker, sVEGFR-1>350 pg/ml, was predictive of DHF. CONCLUSION: The changes in VEGF and its soluble receptors highlight the importance of vascular permeability cytokines in the pathogenesis of DHF.
Subject(s)
Dengue Virus/pathogenicity , Dengue , Receptors, Vascular Endothelial Growth Factor/blood , Severe Dengue , Vascular Endothelial Growth Factor A/blood , Adult , Case-Control Studies , Dengue/blood , Dengue/physiopathology , Dengue/virology , Female , Humans , Male , Severe Dengue/blood , Severe Dengue/physiopathology , Severe Dengue/virology , Solubility , Vascular Endothelial Growth Factor Receptor-1/blood , Vascular Endothelial Growth Factor Receptor-2/bloodABSTRACT
Botulinum toxin (BTX) is an important therapeutic tool in the treatment of overactive skeletal and smooth muscles, as well as hypersecretory and painful disorders. Despite advances in our understanding of how BTX works, much remains to be elucidated, such as how BTX ameliorates pain, how it produces weakness remote from the site of injection and the fate of the heavy and light chain components of the BTX molecule following endocytosis into the presynaptic membrane. BTX, conjugated to radionuclides, allows investigators to track the molecule both in vitro and in vivo. However, altering the BTX molecule may cause structural changes or pharmacokinetic and pharmacodynamic alterations, and disrupt its normal action. We propose instead to bind the biomarkers (appropriate dyes, radionuclides or MRI contrast agents) to monoclonal antibodies directed against either heavy or light chain components of BTX, thus allowing administration of native (i.e. unaltered) BTX.