No abstract

Background: Oxidative stress and inflammation are considered to be important pathways leading to particulate matter (PM)-associated disease. In this exploratory study, we examined the effects of metals and oxidative potential (OP) in urban PM on biomarkers of systemic inflammation, oxidative stress and neural function. Methods: Fifty-three healthy non-smoking volunteers (mean age 28 years, twenty-eight females) were exposed to coarse (2.5–10 μm, mean 213 μg/m3), fine (0.15–2.5 μm, 238 μg/m3), and/or ultrafine concentrated ambient PM (<0.3 μm, 136 μg/m3). Exposures lasted 130 minutes, separated by ≥2 weeks. Metal concentrations and OP (measured by ascorbate and glutathione depletion in synthetic airway fluid) in PM were analyzed. Blood and urine samples were collected pre-exposure, and 1-hour and 21-hour post exposure for assessment of biomarkers. We used mixed-regression models to analyze associations adjusting for PM size and mass concentration. Results: Results for metals were expressed as change (%) from daily pre-exposure biomarker levels after exposure to a metal at a level equivalent to the mean concentration. Exposure to various metals (silver, aluminum, barium, copper, iron, potassium, lithium, nickel, tin, and/or vanadium) was significantly associated with increased levels of various blood or urinary biomarkers. For example, the blood inflammatory marker vascular endothelia growth factor (VEGF) increased 5.3% (95% confidence interval: 0.3%, 10.2%) 1-hr post exposure to nickel; the traumatic brain injury marker ubiquitin C-terminal hydrolase L1 (UCHL1) increased 11% (1.2%, 21%) and 14% (0.3%, 29%) 1-hr and 21-hr post exposure to barium, respectively; and the systemic stress marker cortisol increased 1.5% (0%, 2.9%) and 1.5% (0.5%, 2.8%) 1-hr and 21-hr post exposure to silver, respectively. Urinary DNA oxidation marker 8-hydroxy-deoxy-guanosine increased 14% (6.4%, 21%) 1-hr post exposure to copper; urinary neural marker vanillylmandelic acid increased 29% (3%, 54%) 1-hr post exposure to aluminum; and urinary cortisol increased 88% (0.9%, 176%) 1-hr post exposure to vanadium. Results for OP were expressed as change (%) from daily pre-exposure biomarker levels after exposure to ascorbate-related OP at a level equivalent to the mean concentration, or for exposure to glutathione-related OP at a level above the limit of detection. Exposure to ascorbate- or glutathione-related OP was significantly associated with increased inflammatory and neural biomarkers including interleukin-6, VEGF, UCHL1, and S100 calcium-binding protein B in blood, and malondialdehyde and 8-hydroxy-deoxy-guanosine in urine. For example, UCHL1 increased 9.4% (1.8%, 17%) in blood 21-hr post exposure to ascorbate-related OP, while urinary malondialdehyde increased 19% (3.6%, 35%) and 8-hydroxy-deoxy-guanosine increased 24% (2.9%, 48%) 21-hr post exposure to ascorbate- and glutathione-related OP, respectively. Conclusion: Our results from this exploratory study suggest that metal constituents and OP in ambient PM may influence biomark...

Shutt RH, Howlett SE. Hypothermia increases the gain of excitation-contraction coupling in guinea pig ventricular myocytes.

Background Epidemiological studies have reported associations between air pollution and neuro-psychological conditions. Biological mechanisms behind these findings are still not clear. Objectives We examined changes in blood and urinary neural biomarkers following exposure to concentrated ambient coarse, fine and ultrafine particles. Methods Fifty healthy non-smoking volunteers, mean age 28 years, were exposed to coarse (2.5-10 μm, mean 213 μg/m3) and fine (0.15-2.5 μm, mean 238 μg/m3) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (mean size 59.6 nm, range 47.0-69.8 nm, mean 136 μg/m3) and filtered medical air. Exposures lasted 130 minutes, separated by ≥2 weeks, and the biological constituents endotoxin and β-1,3-D-glucan of each particle size fraction were measured. Blood and urine samples were collected pre-exposure, and 1-hour and 21-hour post exposure to determine neural biomarker levels. Mixed-model regressions assessed associations between exposures and changes in biomarker levels. Results Results were expressed as percent change from daily pre-exposure biomarker levels. Exposure to coarse CAP was significantly associated with increased urinary levels of the stress-related biomarkers vanillylmandelic acid (VMA) and cortisol when compared with exposure to filtered medical air [20% (95% confidence interval: 1.0%, 38%) and 64% (0.2%, 127%), respectively] 21 hours post exposure. However exposure to coarse CAP was significantly associated with decreases in blood cortisol [-26.0% (-42.4%, -9.6%) and -22.4% (-43.7%, -1.1%) at 1 hr and 21 hr post exposure, respectively]. Biological molecules present in coarse CAP were significantly associated with blood biomarkers indicative of blood brain barrier integrity. Endotoxin content was significantly associated with increased blood ubiquitin C-terminal hydrolase L1 [UCHL1, 11 % (5.3%, 16%) per ln(ng/m3+1)] 1-hour post exposure, while β-1,3-D-glucan was significantly associated with increased blood S100B [6.3% (3.2%, 9.4%) per ln(ng/m3+1)], as well as UCHL1 [3.1% (0.4%, 5.9%) per ln(ng/m3+1)], one-hour post exposure. Fine CAP was marginally associated with increased blood UCHL1 when compared with exposure to filtered medical air [17.7% (-1.7%, 37.2%), p=0.07] 21 hours post exposure. Ultrafine CAP was not significantly associated with changes in any blood and urinary neural biomarkers examined. Conclusion Ambient coarse particulate matter and its biological constituents may influence neural biomarker levels that reflect perturbations of blood-brain barrier integrity and systemic stress response.

Objective:To examine cardio-respiratory effects of air pollution in rural older adults exercising outdoors.Methods:Adults 55 and over completed measurements of blood pressure, peak expiratory flow and oximetry daily, and of heart rate variability, endothelial function, spirometry, fraction of exhaled nitric oxide and urinary oxidative stress markers weekly, before and after outdoor exercise, for 10 weeks. Data were analyzed using linear mixed effect models.Results:Pooled estimates combining 2013 (n = 36 participants) and 2014 (n = 41) indicated that an interquartile increase in the air quality health index (AQHI) was associated with a significant (P < 0.05) increase in heart rate (2.1%) and significant decreases in high frequency power (−19.1%), root mean square of successive differences (−9.5%), and reactive hyperemia index (−6.5%).Conclusions:We observed acute subclinical adverse effects of air pollution in rural older adults exercising outdoors.