Aims: Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed ‘spot’ samples showed strong correlations with 24 h excretion (the ‘gold’ standard) of urinary 8-oxodG (r p 0.67–0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended. Antioxid. Redox Signal. 18, 2377–2391.
27 January 2004 in Rapid Communications in Mass Spectrometry
This study evaluates oxidative DNA damage in workers who are exposed to cooking oil fumes (COFs) in Chinese restaurants. The study participants were 387 nonsmoking Chinese restaurant workers, 202 kitchen staff, and 185 service staff at 23 Chinese restaurants in Taiwan. Airborne particulate matter and particulate polycyclic aromatic hydrocarbon levels were monitored in kitchens and dining areas. Urinary 1-hydroxypyrene (1-OHP) was used as an internal dose of exposure to COFs, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was used as an oxidative DNA damage marker. The relationship between workers' 8-OHdG and 1-OHP levels was estimated using linear mixed-effects models. Airborne particulate matter and polycyclic aromatic hydrocarbons levels in kitchens significantly exceeded those in dining areas. The kitchen staff's geometric mean levels of urinary 8-OHdG (7.9 μg/g creatinine) and 1-OHP (4.5 μg/g creatinine) were significantly higher than those of the service staff, which were 5.4 and 2.7 μg/g creatinine, respectively. Urinary 1-OHP level, work in kitchens, gender, and work hours per day were four significant predictors of urinary 8-OHdG levels after adjustments are made for covariates. Oxidative DNA damage was associated with exposure of Chinese restaurant workers to COFs. Female restaurant workers had a greater oxidative stress response to COFs than male restaurant workers, providing additional evidence of the link between lung cancer in Chinese women and exposure to COFs. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3351–7)
1 September 2004 in Environmental Science & Technology
Background and Objectives. Robot-assisted therapy (RT) is a current promising intervention in stroke rehabilitation, but more research is warranted for examining its efficacy and the dose–benefit relation. The authors investigated the effects of higher intensity versus lower intensity RT on movements of forearm pronation–supination and wrist flexion–extension relative to conventional rehabilitation (CR) in patients poststroke for a mean of 21 months. Methods. In this pilot study, 18 patients with initial mean Fugl-Meyer Assessment (FMA) of 37 to 44 for the upper extremity were randomized to higher intensity RT, lower intensity RT, or CR intervention for 4 weeks. The dose of the higher intensity RT was twice the number of repetitions in the lower intensity RT. Outcome measures at pretreatment and posttreatment were administered to patients to evaluate beneficial and adverse effects of interventions. Primary outcomes were the FMA and Medical Research Council scale. Results. There were significant differences in motor function (P = .04) and daily performance (P = .03) among the 3 groups. The higher intensity RT group showed better improvement in motor function, muscle strength, performance of daily activities, and bimanual ability than the other 2 groups. The intensive RT intervention did not induce higher levels of an oxidative DNA biomarker. Conclusions. Higher intensity of RT that assists forearm and wrist movements may lead to greater improvement in motor ability and functional performance in stroke patients. A sample size of only 20 to 25 in each arm of a larger randomized controlled trial is needed to confirm the findings for similar subjects.
The total surface area is known to be an effective exposure metric for predicting the lung toxicity of low solubility nanoparticles (NPs). However, if NPs are dissolved quickly enough in the lungs, the mass may be correlated with the toxicity. Recent studies have found that the toxicity of zinc oxide (ZnO) NPs was caused by the release of zinc ions. Thus, we hypothesized that mass could be used as an exposure metric for the toxicity of ZnO NPs. Healthy Sprague-Dawley rats were exposed to a low, moderate, or high dose of 35 and 250 nm ZnO particles or filtered air. Bronchoalveolar lavage fluid was collected to determine lung inflammation, injury and oxidative stress. The lung inflammation induced by ZnO particles according to different concentration metrics, including number, mass and surface area, was compared. The mass concentration was significantly correlated with the percentage of neutrophils (R(2) = 0.84), number of neutrophils (R(2) = 0.84) and total cells (R(2) = 0.73). Similarly, surface area concentration was significantly correlated with the percentage of neutrophils (R(2) = 0.94), number of neutrophils (R(2) = 0.81) and total cells (R(2) = 0.76). There was no correlation between the number and lung inflammation. We found that both mass and surface area were effective as metrics for the toxicity of ZnO NPs, although only surface area was previously indicated to be an effective metric. Our results are also consistent with recent study results that ZnO NPs and released zinc ions may play a role mediating the toxicity of NPs.