Search

In the frame of the OFFICAIR project, office buildings were investigated across Europe to assess how the office workers are exposed to different particulate matter (PM) characteristics (i.e. PM2.5 mass concentration, particulate oxidative potential (OP) based on ascorbate and reduced glutathione depletion, trace element concentration and total particle number concentration (PNC)) within the buildings. Two offices per building were investigated during the working hours (5 consecutive days; 8 h per day) in two campaigns. Differences were observed for all parameters across the office buildings. Our results indicate that the monitoring of the PM2.5 mass concentration in different offices within a building might not reflect the spatial variation of the health relevant PM characteristics such as particulate OP or the concentration of certain trace elements (e.g., Cu, Fe), since larger differences were apparent within a building for these parameters compared to that obtained for the PM2.5 mass concentration in many cases. The temporal variation was larger for almost all PM characteristics (except for the concentration of Mn) than the spatial differences within the office buildings. These findings indicate that repeated or long-term monitoring campaigns are necessary to have information about the temporal variation of the PM characteristics. However, spatial variation in exposure levels within an office building may cause substantial differences in total exposure in the long term. We did not find strong associations between the investigated indoor activities such as printing or windows opening and the PNC values. This might be caused by the large number of factors affecting PNC indoors and outdoors. © 2017 Elsevier B.V.

In the frame of the OFFICAIR project, indoor and outdoor PM2.5 samples were collected in office buildings across Europe in two sampling campaigns (summer and winter). The ability of the particles to deplete physiologically relevant antioxidants (ascorbic acid (AA), reduced glutathione (GSH)) in a synthetic respiratory tract lining fluid, i.e., oxidative potential (OP), was assessed. Furthermore, the link between particulate OP and the concentration of the PM constituents was investigated.The mean indoor PM2.5 mass concentration values were substantially lower than the related outdoor values with a mean indoor/outdoor PM2.5 mass concentration ratio of 0.62 and 0.61 for the summer and winter campaigns respectively. The OP of PM2.5 varied markedly across Europe with the highest outdoor OPAA m−3 and OPGSH m−3 (% antioxidant depletion/m3 air) values obtained for Hungary, while PM2.5 collected in Finland exhibited the lowest values. Seasonal variation could be observed for both indoor and outdoor OPAA m−3 and OPGSH m−3 with higher mean values during winter. The indoor/outdoor OPAA m−3 and OPGSH m−3 ratios were less than one with 4 and 17 exceptions out of the 40 cases respectively. These results indicate that indoor air is generally less oxidatively challenging than outdoors. Correlation analysis revealed that trace elements play an important role in determining OP, in particular, the Cu content. Indoor air chemistry might affect OP since weaker correlations were obtained for indoor PM2.5. Our findings also suggest that office workers may be exposed to health relevant PM constituents to a different extent within the same building. Keywords: Environmental health, Indoor air quality, Occupational exposure, Office building, Oxidative potential, PM2.5

Many studies have demonstrated associations between exposure to ambient particulate matter (PM) and adverse health outcomes in humans that can be explained by PM capacity to induce oxidative stress in vivo. Thus, assays have been developed to quantify the oxidative potential (OP) of PM as a more refined exposure metric than PM mass alone. Only a small number of studies have compared different acellular OP measurements for a given set of ambient PM samples. Yet, fewer studies have compared different assays over a year long period and with detailed chemical characterization of ambient PM. In this study, we report on seasonal variations of the dithiothreitol (DTT), ascorbic acid (AA), electron spin resonance (ESR) and the respiratory tract lining fluid (RTLF, composed of the reduced glutathione (GSH) and ascorbic acid (ASC)) assays over a one year period in which 100 samples were analysed. A detailed PM10 characterization allowed univariate and multivariate regression analyses in order to obtain further insight into groups of chemical species that drive OP measurements. Our results show that most of the OP assays were strongly inter-correlated over the sampling year but also these correlations differed when considering specific sampling periods (cold vs war). All acellular assays are correlated with a significant number of chemical species when considering univariate correlations, especially for the DTT assay. Evidence is also presented of a seasonal contrast over the sampling period with significantly higher OP values during winter for the DTT, AA, GSH and ASC assays, which were assigned to biomass burning species by the multiple linear regression models. The ESR assay clearly differs from the other tests as it did not show seasonal dynamics and presented weaker correlations with other assays and chemical species.

Road widening schemes in urban areas are often proposed as a solution to traffic congestion and as a means of stimulating economic growth. There is however clear evidence that new or expanded roads rapidly fill with either displaced or induced traffic, offsetting any short-term gains in eased traffic flows. What has not been addressed in any great detail is the impact of such schemes on air quality, with modelled impact predictions seldom validated by measurements after the expansion of road capacity. In this study we made use of a road widening project in London to investigate the impact on ambient air quality (particulate matter, NOX, NO2) during and after the completion of the road works. PM10 increased during the construction period up to 15 μg m(-3) during working hours compared to concentrations before the road works. A box modelling approach was used to determine a median emission factor of 0.0022 kg PM10 m(-2) month(-1), three times larger than that used in the UK emission inventory (0.0007 kg PM10 m(-2) month(-1)). Peaks of activity released 0.0130 kg PM10 m(-2) month(-1), three and eight times smaller than the peak values used in the European and US inventories. After the completion of the widening there was an increase in all pollutants from the road during rush hour: 2-4 μg m(-3) for PM10; 1 μg m(-3) for PM2.5; 40 and 8 μg m(-3) for NOX and NO2, respectively. NO2 EU Limit Value was breached after the road development illustrating a notable deterioration in residential air quality. Additionally, PM10, but not PM2.5, glutathione dependent oxidative potential increased after the road was widened consistent with an increase in pro-oxidant components in the coarse particle mode, related to vehicle abrasion processes. These increased air pollution indices were associated with an increase in the number of cars, taxis and LGVs.

Fifty samples of indoor and outdoor PM 2.5 were collected onto quartz fiber and Teflon membrane filters in five office buildings equipped with heating, ventilation and air-conditioning system for 8 h daily in order to coincide with the work shift of employees. Samples were analyzed for i) mass concentration; ii) elemental concentration; and iii) oxidative potential (OP) through antioxidant depletion. The PM 2.5 mass concentration exceeded the annual mean guideline of 10 μg m −3 WHO in 50% of the samples. Indoor and outdoor PM 2.5 mass concentrations correlated almost linearly. Proton-induced X-ray emission (PIXE) spectrometry was used for the monitoring of 21 elements. Quantitative determination was achieved in the case of Teflon filters only for Al, Si, S, Cl, K, Ca, Ti, Cr, Mn, Fe and Zn at ng m −3 concentration level. Quartz fiber filters were less adequate for the PIXE measurements due to their greater thickness and filamentary structure. Ca, Cr, Zn and Ti had generally higher concentration (mg g −1 ) indoors. Indoor/outdoor (I/O) OP values were higher than one in 14% and 57% of the samples in the case of ascorbate and reduced glutathione (GSH), respectively. Spatial and temporal variations of OP were observed across the office buildings. The I/O ratios for OP, Cr and Zn concentrations in the case of GSH were higher for three buildings. Significant relationship was observed between GSH oxidation and Cr and Zn concentrations. Thus, employees were exposed to a higher extent to reactive oxygen species in three buildings.

Ashfall into heavily populated areas during the October–November 2010 eruption of Merapi volcano, Indonesia created anxiety regarding the growing impacts to health as the eruption escalated and the hazard zone widened. We made a preliminary assessment of the respiratory hazards to human health of the tephra deposits (ashfall, lahar, and PDC surge) from the eruption using a laboratory protocol specifically developed to study the toxic potential of volcanic ash particles. Twenty samples collected from a range of locations were analysed for health-pertinent mineralogical parameters (grain size, crystalline silica content, morphology, surface area, bulk chemistry, and leachable elements) and bio-reactivity (hydroxyl radical generation, haemolytic potential, oxidative capacity, pro-inflammatory response). The grain size pertinent to respiratory health was variable, ranging from 1.4–15.6 vol.% sub-4 μm and 3.0–28.9 vol.% sub-10 μm diameter material. No fibre-like particles were observed. Cristobalite was present in all samples, ranging from 1.9–9.5 wt.%, but surface reactivity and in vitro toxicity assays showed low reactivity for all samples tested. The risk of direct exposure to ash from fallout was in any case low due to seasonal rains limiting its re-suspension and the immediate and effective clean-up of communities by local people who supplied the ash to the Indonesian construction industry for use as aggregate. However, mining of the lahar and thick PDC deposits in the valleys draining the volcano is performed on a vast, industrial scale, which could result in high occupational exposure to thousands of sand miners at Merapi during the dry seasons. Further study of the health hazard of the mined Merapi deposits is warranted

Concentrations of total suspended particulate matter, particulate matter with aerodynamic diameter 2.5), particulate matter 10), and fallout dust were measured at the Iranian Gol-E-Gohar Mining and Industrial Facility. Samples were characterized in terms of mineralogy, morphology, and oxidative potential. Results show that indoor samples exceeded the 24-h PM2.5 and PM10 mass concentration limits (35 and 150 µg m−3, respectively) set by the US National Ambient Air Quality Standards. Calcite, magnetite, tremolite, pyrite, talc, and clay minerals such as kaolinite, vermiculite, and illite are the major phases of the iron ore PM. Accessory minerals are quartz, dolomite, hematite, actinolite, biotite, albite, nimite, laumontite, diopside, and muscovite. The scanning electron microscope structure of fibrous-elongated minerals revealed individual fibers in the range of 1.5 nm to 71.65 µm in length and 0.2 nm to 3.7 µm in diameter. The presence of minerals related to respiratory diseases, such as talc, crystalline silica, and needle-shaped minerals like amphibole asbestos (tremolite and actinolite), strongly suggests the need for detailed health-based studies in the region. The particulate samples show low to medium oxidative potential per unit of mass, in relation to an urban road side control, being more reactive with ascorbate than with glutathione or urate. However, the PM oxidative potential per volume of air is exceptionally high, confirming that the workers are exposed to a considerable oxidative environment. PM released by iron ore mining and processing activities should be considered a potential health risk to the mine workers and nearby employees, and strategies to combat the issue are suggested.

Sugarcane combustion generates fine-grained particulate that has the potential to be a respiratory health hazard because of its grain size and composition. In particular, conversion of amorphous silica to crystalline forms during burning may provide a source of toxic particles. In this study, we investigate and evaluate the toxicity of sugarcane ash and bagasse ash formed from commercial sugarcane burning. Experiments to determine the main physicochemical properties of the particles, known to modulate biological responses, were combined with cellular toxicity assays to gain insight into the potential reactions that could occur at the particle-lung interface following inhalation. The specific surface area of the particles ranged from ∼16 to 90 m(2) g(-1) . The samples did not generate hydroxyl- or carbon-centered radicals in cell-free tests. However, all samples were able to 'scavenge' an external source of hydroxyl radicals, which may be indicative of defects on the particle surfaces that may interfere with cellular processes. The bioavailable iron on the particle surfaces was low (2-3 μmol m(-2) ), indicating a low propensity for iron-catalyzed radical generation. The sample surfaces were all hydrophilic and slightly acidic, which may be due to the presence of oxygenated (functional) groups. The ability to cause oxidative stress and membrane rupture in red blood cells (hemolysis) was found to be low, indicating that the samples are not toxic by the mechanisms tested. Cytotoxicity of sugarcane ash was observed, by measuring lactate dehydrogenase release, after incubation of relatively high concentrations of ash with murine alveolar macrophage cells. All samples induced nitrogen oxide release (although only at very high concentrations) and reactive oxygen species generation (although the bagasse samples were less potent than the sugarcane ash). However, the samples induced significantly lower cytotoxic effects and nitrogen oxide generation when compared with the positive control.

This study isolated the effects of maternal hypoxia independent of changes in maternal nutrition on maternal circulatory and placental molecular indices of oxidative stress and determined whether maternal antioxidant treatment conferred protection. Pregnant rats were subjected to normoxic pregnancy or 13% O2 chronic hypoxia for most of gestation with and without maternal treatment with vitamin C in the drinking water. Maternal hypoxia with and without vitamin C did not affect maternal food or water intake and led to a significant increase in maternal and fetal haematocrit. At gestational day 20, maternal plasma urate and L-cysteine concentrations, and placental levels of 4-hydroxynonenal and heat shock protein 70 were increased while placental heat shock protein 90 levels were decreased in hypoxic pregnancy. The induction of maternal circulatory and placental molecular indices of oxidative stress in hypoxic pregnancies was prevented by maternal treatment with vitamin C. Maternal hypoxia during pregnancy with or without vitamin C increased placental weight, but not total or compartmental volumes. Maternal treatment with vitamin C increased birth weight in both hypoxic and normoxic pregnancies. The data show that maternal hypoxia independent of maternal undernutrition promotes maternal and placental indices of oxidative stress, effects that can be prevented by maternal treatment with vitamin C in hypoxic pregnancy. While vitamin C may not be the ideal candidate of choice for therapy in pregnant women, and taking into consideration differences in ascorbic acid metabolism between rats and humans, the data do underlie that antioxidant treatment may provide a useful intervention to improve placental function and protect fetal growth in pregnancy complicated by fetal hypoxia.

Episodes of hypoxia in utero present a potentially serious challenge to the fetus, but are counteracted by defence responses including marked redistribution of blood flow from peripheral circulations to the brain. Here, we report the novel observation that the oxidant tone is an important modulator of this cardiovascular defence. Using pregnant Welsh Mountain sheep surgically prepared for long-term recording, we investigated in vivo the effects on the fetal cardiovascular defence to acute hypoxaemia of fetal treatment with the antioxidant vitamin C. The mechanisms via which vitamin C may affect the vascular oxidant tone were investigated by monitoring fetal plasma concentrations of nitrates and nitrites, by determining changes in the activity of superoxide dismutase (SOD) in fetal plasma, and by investigating the effect of vitamin C treatment on the fetal cardiovascular defence to hypoxaemia following nitric oxide (NO) synthase blockade. Fetal treatment with vitamin C markedly depressed the normal femoral constrictor response to acute hypoxaemia in the fetus (5.2 ± 1.0 vs. 1.1 ± 0.3 mmHg (ml min−1)−1, mean ±s.e.m.; P < 0.05) an effect which was completely restored following NO synthase blockade (6.2 ± 1.3 mmHg (ml min−1)−1). Compared to saline infusion, fetal treatment with vitamin C during acute hypoxaemia also significantly increased fetal plasma SOD activity from normoxic baseline (−8.9 ± 6.5 vs. 15.0 ± 6.6% inhibition, P < 0.05) and decreased the plasma concentration ratio of nitrate:nitrite from normoxic baseline (ΔNO3−:NO2−; 0.15 ± 0.30 vs. −0.29 ± 0.11, P < 0.05). The data provide in vivo evidence of redox modulation of redistribution of blood flow in the fetus, part of the fetal brain sparing during acute hypoxaemic stress.

An integrated approach has been developed for the multi-component analysis of indoor PM2.5 collected onto the same quartz fiber filter (QFF) by using an innovative combination of techniques such as inductively coupled sector field plasma mass spectrometry (ICP-SF-MS) with vapor-phase microwave-assisted aqua regia or sonication-assisted water extraction, ion chromatography, thermal-optical transmittance as well as high performance liquid chromatography and enzyme-linked 5,5'-dithio-bis(2-nitrobenzoic acid) assay for the determination of elemental composition, major inorganic ions, elemental/organic carbon (EC/OC) as well as oxidative potential (OP) through ascorbate (AA) and reduced glutathione (GSH) depletion, respectively. The low mass of PM2.5 collectable indoors, the elemental blank values of the QFFs and the sample volume/acidity requirements of the ICP-SF-MS represented a challenge for elemental determination. Finally, this approach was successfully applied for determination of 15 elements (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Rb, Sr, Mo, Cd, Sn and Pb) at the ngm-3 level in more than two-thirds of indoor PM2.5 (n=25) collected in mechanically ventilated offices within the European Union project OFFICAIR at increased sampling flow rates (0.6m3h-1-2.3m3h-1) and sampling time (cca. 100h) in the acidic/aqueous extracts. The concentration of Cl-, NO3 -, SO4 2-, Na+, NH4 +, K+, Ca2+, Mg2+, OC and EC was at the μgm-3 level in the aqueous extracts. This new approach aiming at the comprehensive characterization of low mass indoor PM2.5 samples allowed assessment of OPAA and OPGSH in all samples. The PM2.5 critical sample mass to achieve elemental determination was approximately 400μg.

The hypothesis was tested that Werner syndrome (WS) phenotype might be associated with an in vivo prooxidant state. A set of redox-related endpoints were measured in three WS patients, two of their parents, and 99 controls within a study of some cancer-prone and/or ageing-related genetic disorders. The following analytes were measured: (a) leukocyte 8-hydroxy-2'-deoxyguanosine; (b) glutathione from whole blood, and (c) plasma levels of glyoxal, methylglyoxal, 8-isoprostane, and some plasma antioxidants (uric acid, ascorbic acid, alpha- and gamma-tocopherol). Leukocyte 8-hydroxy-2'-deoxyguanosine levels showed a significant increase in the 3 WS patients vs. 85 controls (p

The first-trimester human placenta has limited antioxidant enzyme capacity. We investigated the distribution and transfer pathways of antioxidant molecules inside the first trimester gestational sac. The coelomic fluid of the exocoelomic cavity, which borders the inside of the first-trimester placenta, contained a very low level of reduced glutathione. Glutathione disulfide was undetectable in most coelomic samples, suggesting that the role of glutathione-related detoxification system is limited in fetal fluid compartments. The coelomic fluid contained similar concentrations of ascorbic and uric acid to maternal plasma. The levels of alpha- and gamma-tocopherol were lower in coelomic fluid, compared with maternal plasma. The presence of these molecules inside the early gestational sac suggests that they may play an essential role in the fetal tissues' antioxidant capacity at a time when the fetus is most vulnerable to oxidative stress. We also demonstrated by immunostaining the presence of alpha-tocopherol transfer protein in the cytoplasm of trophoblastic cells, glandular epithelium of the decidua, and mesothelial layer of the secondary yolk sac. This finding indicates that the uterine glands and the secondary yolk sac play key roles in supplying this essential vitamin to the developing fetus before the placental circulations are established.

Hypochlorous acid (HOCl), generated by myeloperoxidase released from activated macrophages, is thought to contribute to vascular dysfunction and oxidation of low density lipoproteins (LDLs) in atherogenesis. We have previously shown that HOCl exposure can cause chlorination and oxidation of isolated DNA and that vitamin C protects human arterial smooth muscle cells against oxidized LDL–mediated damage. We report in the present study that vitamin C attenuates HOCl-induced DNA base and protein damage and depletion of intracellular glutathione (GSH) and ATP in human arterial smooth muscle cells. Cells were pretreated in the absence or presence of 100 μmol/L vitamin C (24 hours) and then exposed to HOCl (0 to 500 μmol/L, 0 to 60 minutes) in the absence of vitamin C. Intracellular GSH and ATP levels were depleted by HOCl treatment, and gas chromatography–mass spectroscopy revealed a concentration- and time-dependent increase in DNA base oxidation and protein damage (measured as 3-chlorotyrosine). Pretreatment of smooth muscle cells with vitamin C significantly reduced the extent of HOCl-induced DNA and protein damage and attenuated decreases in intracellular ATP and GSH. Our findings suggest that physiological levels of vitamin C provide an important antioxidant defense against HOCl-mediated injury in atherosclerosis.

Alpha- and gamma-tocopherol (alpha- and gamma-T, respectively) metabolite analysis is of key relevance in the study of vitamin E metabolism. Whilst there is information on urinary excretion of the two major metabolites of these vitamin E homologues, namely the 2,5,7,8-tetramethyl-2-(beta-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), their concentration and response to supplements in plasma remains poorly investigated. In this study we describe a gas chromatography-mass spectrometry (GC/MS)-based assay to measure both alpha- and gamma-T and their corresponding CEHC metabolites in human plasma. As an example of the application of this method we report data obtained following the supplemention of two healthy volunteers with 100 mg of deuterium-labeled gamma-T acetate (d(2)-gamma-TAC). Under routine analytical conditions a good linearity in the range 0.0025--1 microM was observed for both the alpha- and gamma-CEHC deuterated standards. In plasma samples, the detection limit for alpha- and gamma-CEHC was 2.5 and 5 nmol/l, respectively. The minimum amount of plasma required for the assay was 500 microl. The plasma concentrations of alpha-CEHC and gamma-CEHC in unsupplemented healthy subjects were 12.6 +/-7.5 and 160.7 +/- 44.9 nmol/l, respectively. In the two volunteers supplemented with 100 mg of d(2)-gamma-TAC, plasma d(2)-gamma-T concentrations increased 250 to 450-fold 6 h postsupplementation. Plasma and urinary d(2)-gamma-CEHC concentrations increased 20 to 40-fold 9--12 h postsupplementation. Interestingly, the acute increase in d(2) gamma-T did not significantly affect the baseline plasma concentrations of d(0)-gamma-T and only slight lowered alpha-T concentrations. Likewise, plasma alpha-CEHC levels were not influenced and urinary excretion of alpha-CEHC were unaltered. This GC/MS method provides a versatile and accurate mean for assessing carboxyethyl-hydroxychroman metabolites of vitamin E in plasma.

A comprehensive chemical characterization and oxidative potential (OP) assessment of PM2.5 was carried out at an urban site of Budapest between June 2010 and May 2013 to investigate the seasonal variability of particulate phase air pollutants and their oxidative activity. Chemical analyses included the determination of the concentration of trace elements, major water-soluble inorganic ions and carbonaceous fractions (total carbon, water-soluble organic carbon, organic carbon, elemental carbon). The OP of PM2.5 was assessed by antioxidant depletion using a synthetic respiratory tract lining fluid containing ascorbate, reduced glutathione and urate. The mean PM2.5 mass concentration (21.0 μg m(-3)) was just below the 25 μg m(-3) annual mean PM2.5 limit value set by the European Commission and showed a seasonal pattern with higher levels during winter. On average, 84% of the gravimetric mass could be reconstructed by the chemical measurements. Organic matter and secondary inorganic ions were the most dominant PM2.5 constituents contributing 40 and 29% of its mass, respectively. Changes in the yearly concentrations were not identified for the investigated compounds between 2010 and 2013. Temporal differences in both ascorbate and glutathione oxidation could be observed during the 3-year long sampling period; however, no clear seasonal trend was apparent. OP metrics were associated mainly with traffic-related trace elements; however, other PM sources (i.e., long-range transport, secondary aerosol formation) could also contribute to particulate OP in Budapest. The weak correlation between OP metrics and PM2.5 mass concentration suggests the possibility of using OP as an additional metric in epidemiology.

Sugarcane combustion generates fine-grained particulate that has the potential to be a respiratory health hazard because of its grain size and composition. In particular, conversion of amorphous silica to crystalline forms during burning may provide a source of toxic particles. In this study, we investigate and evaluate the toxicity of sugarcane ash and bagasse ash formed from commercial sugarcane burning. Experiments to determine the main physicochemical properties of the particles, known to modulate biological responses, were combined with cellular toxicity assays to gain insight into the potential reactions that could occur at the particle-lung interface following inhalation. The specific surface area of the particles ranged from ∼16 to 90 m(2) g(-1) . The samples did not generate hydroxyl- or carbon-centered radicals in cell-free tests. However, all samples were able to 'scavenge' an external source of hydroxyl radicals, which may be indicative of defects on the particle surfaces that may interfere with cellular processes. The bioavailable iron on the particle surfaces was low (2-3 μmol m(-2) ), indicating a low propensity for iron-catalyzed radical generation. The sample surfaces were all hydrophilic and slightly acidic, which may be due to the presence of oxygenated (functional) groups. The ability to cause oxidative stress and membrane rupture in red blood cells (hemolysis) was found to be low, indicating that the samples are not toxic by the mechanisms tested. Cytotoxicity of sugarcane ash was observed, by measuring lactate dehydrogenase release, after incubation of relatively high concentrations of ash with murine alveolar macrophage cells. All samples induced nitrogen oxide release (although only at very high concentrations) and reactive oxygen species generation (although the bagasse samples were less potent than the sugarcane ash). However, the samples induced significantly lower cytotoxic effects and nitrogen oxide generation when compared with the positive control.

More than half the world's population still rely on burning biomass fuels to heat and light their homes and cook food. Household air pollution, a common component of which is inhalable particulate matter (PM), emitted from biomass burning is associated with increased vulnerability to respiratory infection and an enhanced risk of developing chronic obstructive pulmonary disease. In the light of an emerging hypothesis linking chronic PM exposure during childhood and increased vulnerability to respiratory diseases in adulthood, in a chain of events involving oxidative stress, reduced immunity and subsequent infection, the aim of this study was to characterise the oxidative potential (OP) of PM collected during the burning of wood and mixed biomass, whilst cooking food in the Kathmandu Valley, Nepal. Our assessments were based on the capacity of the particles to deplete the physiologically relevant antioxidants from a validated, synthetic respiratory tract lining fluid (RTLF). Incubation of mixed biomass and wood smoke particles suspensions with the synthetic RTLF for 4 h resulted in a mean loss of ascorbate of 64.76 ± 16.83% and 83.37 ± 14.12% at 50 μg/ml, respectively. Reduced glutathione was depleted by 49.29 ± 15.22% in mixed biomass and 65.33 ± 13.01% in wood smoke particles under the same conditions. Co-incubation with the transition metal chelator diethylenetriaminepentaacetate did not inhibit the rate of ascorbate oxidation, indicating a negligible contribution by redox-active metals in these samples. The capacity of biomass smoke particles to elicit oxidative stress certainly has the potential to contribute towards negative health impacts associated with traditional domestic fuels in the developing world.

Evidence suggests that oxidative stress is a unifying feature underlying the toxic actions of particulate matter (PM). We have investigated whether individual plasma antioxidant concentrations (uric acid and vitamins C, A, and E) and 10 antioxidant genes modify the response to PM with respect to hospital admissions for chronic obstructive pulmonary disease (COPD) or asthma.Using a bidirectional, hospital-based, case-crossover study, 209 patients admitted for asthma or COPD to the Chelsea and Westminster Hospital (London), with 234 admissions, were recruited between May 2008 and July 2010. PM10 levels in the area of Kensington and Chelsea at the time of admission were compared with the levels 14 days before and 14 days after the event. Conditional logistic regression was used to estimate the effect of PM10 at several temporal lags, while controlling for confounders.An increase in asthma/COPD admission rate was related to a 10 μg/m increase in PM10, with the highest effect noted 0-3 days before the exacerbation (for lag 0-3, odds ratio = 1.35 [95% confidence interval = 1.04-1.76]). Serum vitamin C modified the effect of PM10 on asthma/COPD exacerbations. A similar (although weaker) influence was observed for low levels of uric acid and vitamin E, whereas vitamin A showed no effect modification. GSTP1 (rs1695), SOD2 (rs4880), and Nrf2 (rs1806649) were associated with a trend toward an increased risk of hospital admissions during periods of high PM10 levels.Our study suggests that the concentration of antioxidants in patients' serum modifies the short-term effects of PM10 on asthma and COPD exacerbations.

The continuous ash and gas emissions from the Tavurvur cone in Rabaul caldera, Papua New Guinea, during 2007–08, raised concerns regarding how exposure would affect the respiratory health of nearby populations and impact on the environment. As part of a formal evaluation of the effects of volcanic emissions on public health, we investigated the potential health hazard of the ash using a suite of selected mineralogical analyses and in vitro toxicity screening tests. The trachy-andesitic ash comprised 2.1–6.7 vol.% respirable (sub-4 μm diameter) particles. The crystalline silica content was 1.9–5.0 wt.% cristobalite (in the bulk sample) with trace amounts of quartz and/or tridymite. Scanning electron microscopy showed that the ash particles were angular with sparse, fibre-like particles (∼3–60 μm max. diameter) observed in some samples, which we confirmed to be CaSO4 (gypsum, at

A comparative evaluation is reported of pro-oxidant states in 82 patients with ataxia telangectasia (AT), Bloom syndrome (BS), Down syndrome (DS), Fanconi anemia (FA), Werner syndrome (WS), and xeroderma pigmentosum (XP) vs 98 control donors. These disorders display cancer proneness, and/or early aging, and/or other clinical features. The measured analytes were: (a) leukocyte and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), (b) blood glutathione (GSSG and GSH), (c) plasma glyoxal (Glx) and methylglyoxal (MGlx), and (d) some plasma antioxidants [uric acid (UA) and ascorbic acid (AA)]. Leukocyte 8-OHdG levels ranked as follows: WS>BS approximately FA approximately XP>DS approximately AT approximately controls. Urinary 8-OHdG levels were significantly increased in a total of 22 patients with BS, FA, or XP vs 47 controls. The GSSG:GSH ratio was significantly increased in patients with WS and in young (< or =15 years) patients with DS or with FA and decreased in older patients with DS or FA and in AT, BS, and XP patients. The plasma levels of Glx and/or MGlx were significantly increased in patients with WS, FA, and DS. The UA and AA levels were significantly increased in WS and DS patients, but not in AT, FA, BS, nor XP patients. Rationale for chemoprevention trials is discussed.

Objective: To evaluate an association of Bloom syndrome (BS) phenotype with an in vivo prooxidant state. Methods: The following endpoints were measured in 4 BS patients, their 6 parents, and 78 controls: a) leukocyte and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG); b) blood glutathione (GSSG and GSH), c) plasma levels of some plasma antioxidants (uric acid, UA, ascorbic acid, AA, α- and γ-tocopherol), and of glyoxal (Glx) and methylglyoxal (MGlx). Results: Leukocyte 8-OHdG levels were significantly increased in the 4 BS patients vs. 40 controls (p = 0.04), while the urinary 8-OHdG levels were non-significantly increased in BS patients. Glutathione disulfide levels and GSSG/GSH ratio were significantly decreased in BS patients vs. 44 controls (p = 0.02). The plasma levels of UA in BS patients were significantly increased vs. 24 controls (p = 0.005). No significant alterations were found in the in the plasma levels of Glx, MGlx, AA, and tocopherol. No changes in the tested parameters were found in the BS heterozygotes. Conclusion: This report shows a significant increase in oxidative DNA damage in leukocytes and in plasma UA levels from 4 BS patients. Should these data be confirmed in more extensive BS patient groups, an involvement of oxidative stress in the clinical BS phenotype might be suggested.

Psoriasis is an inflammatory skin disorder that is inherited as a multifactorial trait. Genetic analyses have repeatedly identified a primary disease susceptibility locus lying within the major histocompatibility complex (MHC), on chromosome 6p21. A small number of non-MHC susceptibility loci have also been identified. These regions tend to overlap with susceptibility intervals for Crohn's disease and atopic dermatitis, suggesting the possibility that genetic variants affecting inflammatory pathways may contribute to the pathogenesis of multiple disorders. Here, we report a genetic analysis of the interleukin 23 receptor gene (IL23R), which was recently identified as a susceptibility determinant for Crohn's disease. We initially examined the results of a whole-genome association scan, carried out on 318 cases and 288 controls. We observed a significant increase of a non-synonymous substitution (p.Arg381Gln) among controls (P = 0.00036). We validated this finding by extending our cohort to include a further 519 cases and 528 controls. In the overall sample, the frequency of the 381Gln allele was 3.6% in cases and 7% in controls, yielding a P value of 0.00014. Next, we examined genetic variation at the IL12RB1, IL23A and IL12B genes, respectively, encoding the second subunit of the IL23R receptor and the two subunits of its ligand. This analysis identified independent associations for IL12B SNPs rs10045431 (P value for the extended dataset = 0.0001) and rs3212227 (P = 0.036). Altogether, these findings indicate that genes participating in IL23 signalling play a significant role in the pathogenesis of chronic epithelial inflammation.

Oxidative stress has been associated with Down syndrome (DS) and with its major phenotypic features, such as early ageing. In order to evaluate an in vivo pro-oxidant state, the following analytes were measured in a group of DS patients aged 2 months to 57 years: (a) leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG); (b) blood glutathione; (c) plasma levels of: glyoxal (Glx) and methylglyoxal (MGlx); some antioxidants (uric acid, UA, ascorbic acid, AA and Vitamin E), and xanthine oxidase (XO) activity. A significant 1.5-fold increase in 8-OHdG levels was observed in 28 DS patients vs. 63 controls, with a sharper increase in DS patients aged up to 30 years. The GSSG:GSHx100 ratio was significantly higher in young DS patients (< 15 years), in contrast to DS patients aged >= 15 years that showed a significant decrease in the GSSG:GSHx100 ratio ratio vs. controls of the respective age groups. Plasma Glx levels were significantly higher in young DS patients, whereas no significant difference was detected in DS patients aged >= 15 years. Unlike Glx, the plasma levels of MGlx were found to be significantly lower in DS patients vs. controls. A significant increase was observed in plasma levels of UA in DS patients that could be related to an increased plasma XO activity in DS patients. The plasma concentrations of AA were also increased in young (< 15 years) DS patients, but not in older patients vs. controls in the same age range. The levels of Vitamin E in DS patients did not differ from the values determined in control donors. The evidence for a multiple pro-oxidant state in young DS patients supports the role of oxidative stress in DS phenotype, with relevant distinctions according to patients' ages.

Some selected oxidative stress parameters were measured in 56 Fanconi anaemia (FA) patients (42 untransplanted and 14 transplanted), 54 FA heterozygotes (parents) and 173 controls. Untransplanted FA patients showed a highly significant increase in leukocyte 8-hydroxy-2’-deoxyguanosine (8-OHdG) (p = 0.00003) and a borderline increase (p = 0.076) in urinary levels of 8-OHdG vs. child controls. These increases were more pronounced in female FA patients (p = 0.00005 for leukocyte 8-OHdG, and p = 0.021 for urinary 8-OHdG). Female FA patients also displayed a highly significant excess of spontaneous chromosomal breaks vs. male patients (p = 0.00026), in the same female:male ratio (≅ 1.4) as detected both for leukocyte and for urine 8-OHdG levels. Plasma methylglyoxal (MGlx) levels were increased in untransplanted FA patients vs. child controls (p = 0.032). The increases in leukocyte and urinary 8-OHdG, and in MGlx levels were detected in young FA patients (≤15 yrs), whereas patients aged 16 to 29 yrs failed to display any differences vs. controls in the same age group. A significant increase in oxidised:reduced glutathione (GSSG:GSH) ratio was observed (p = 0.046) in the FA patients aged ≤15 yrs, whereas those aged 16 to 29 yrs, both untransplanted and transplanted, displayed a decrease (p = 0.06) in the GSSG:GSH ratio vs. the controls of the respective age groups. No significant changes were detected in plasma levels of Vitamin C, Vitamin E, or uric acid. Transplanted FA patients showed lesser alterations in leukocyte 8-OHdG and in GSSG:GSH ratio vs. untransplanted patients. The parents of FA patients displayed a significant increase in plasma MGlx levels (p = 0.0014) vs. adult controls. The results suggest a gender- and age-related modulation of oxidative stress in FA patients. The observed increase in urinary 8-OHdG in untransplanted FA patients suggests a proficient removal of oxidised DNA bases. Key words: Fanconi anaemia; 8-hydroxy-2’-deoxyguanosine; methylglyoxal; glutathione; chromosomal instability

The elderly are frequently classified as being particularly susceptible to air pollution. The basis of this increased sensitivity is not known but it is likely that it is linked to age-related impaired function of the lung. However, given this uncertainty and increased impact of air pollution of this section of the community there is a need to explore the mechanisms involved. Gaseous air pollutants such as ozone and nitrogen dioxide, or many of the components adsorbed onto the surface of respirable particles, are either powerful oxidants or capable of generating free radicals. If unabated, oxidants can cause injury to the delicate cells that line the respiratory tract. Small molecular weight antioxidant defences present in respiratory tract lining fluid (RTLF) represent the first line of defence against a range of oxidants that enter the lung. The quantity and quality of the RTLF airways antioxidant network are, therefore, likely to be important determinants of the impact of the oxidant challenge on the underlying respiratory epithelium. As yet, comprehensive information on the distribution and variability of respiratory tract lining fluid antioxidant defences is only available in young, mainly healthy volunteers. Studies undertaken in patients with a range of respiratory diseases suggest that marked changes in the distribution of respiratory tract lining fluid antioxidants can occur. Information is not currently available on the impact of ageing on the respiratory tract lining fluid antioxidant defence network. As several respiratory tract lining fluid antioxidants are of dietary origin, the elderly, who often have different dietary patterns to younger individuals, may have decreased availability of important antioxidants. Given these possibilities, a better understanding of respiratory tract lining fluid antioxidant defences in the aged lung is warranted.

Prolonged low-medium intensity exercise is associated with increased oxidative stress in humans. We hypothesized that competitive equine endurance racing would induce changes in circulatory antioxidants and produce systemic oxidative stress. Forty horses competing in a 140-km endurance race in warm conditions [shade temperature 15-19 degrees C; 62-88% relative humidity (%RH)] were sampled before (Pre), immediately after exercise (End) and at approximately 16 h into recovery (+16 h). Plasma ascorbic acid concentration was not different between Pre [11.1 (median); 4.6-20.3 micromol/L (range)] and End [9.7; 3.0-38.9 (range) micromol/L] but was significantly decreased at +16 h (5.5; 2.8-15.5 micromol/L; P0.05). Total red cell hemolysate glutathione (TGSH) concentration was significantly reduced by exercise (Pre 1261; 883-1532 micromol/L; End 1065; 757-1334 micromol/L; P0.05) and at +16 h recovery (1032; 752-1362 micromol/L; P0.05). Glutathione redox ratio was unchanged by exercise but was significantly decreased at +16 h compared with that at both Pre and End (P0.05). The concentration of total barbituric acid reactive substances (TBARS) in plasma was increased compared with that at Pre (309; 66-1048 nmol/L), both at End (408; 170-1196 nmol/L; P0.05) and +16 h (380; 99-1161 nmol/L; P0.05). alpha-Tocopherol was unchanged by exercise or recovery. Mean race speed was 16.5 +/- 1.6 km/h and ranged from 13.9 to 19.7 km/h. Mean speed during competition in horses that completed the full 140 km (n = 28) was significantly correlated with end of exercise ascorbic acid (r = 0.622; P = 0.0004). Although there were increases in creatine phosphokinase (CK), aspartate aminotransferase (AST) and TBARS and a loss of TGSH, this study failed to demonstrate evidence of classical oxidative stress.

Background — Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation. In experimental left ventricular hypertrophy (LVH), this endothelium-dependent LV relaxant response is impaired despite a preserved response to exogenous NO. We investigated the potential role of reactive oxygen species (ROS) in this defect. Methods and Results — Short-term treatment with the antioxidants vitamin C (10 μmol/L) or deferoxamine (500 μmol/L) restored LV relaxant responses to the NO agonists bradykinin (10 nmol/L) and substance P (100 nmol/L) in isolated ejecting hearts of aortic-banded guinea pigs. Substance P decreased the time to onset of LV relaxation (tdP/dt min ) by −6.8±1.7 ms in the presence of vitamin C and by −8.9±2.2 ms in the presence of deferoxamine compared with −0.8±2.2 ms in the absence of antioxidants ( P l -arginine. Protein expression of the NADPH oxidase subunits gp91- phox and p67- phox and myocardial NADPH oxidase activity were significantly increased ( P Conclusions — An increase in ROS, most likely derived at least in part from NADPH oxidase, is responsible for the impaired endothelial regulation of LV relaxation in LVH. These are the first data to potentially link increased NADPH oxidase-derived ROS with a defect in cardiac contractile function in a pathological setting.

Alpha- and gamma-tocopherol plasma and urinary biokinetics following alpha-tocopherol supplementation.

Publisher Summary Sulfhydryl (thiyl) free radicals can be generated in a variety of biochemical systems, particularly those containing a peroxidase or myoglobin and hydrogen peroxide. They have long been known to be formed thermally, by photolysis, and by radiolysis. They can also be readily formed by sonolysis in systems, such as thiyl free radicals can rapidly undergo electron transfer and hydrogen transfer reactions with a variety of biological molecules. They can also undergo addition reactions with oxygen and with several conjugated olefinic and aromatic compounds including vitamins A and D, styrene, and several polyaromatic dihydrodiols. This chapter discusses the use of vitamin A, the food additive curcumin, and the benzene metabolite muconic acid as reference models in studies of thiyl free radical reactivity together with some of the methods by which thiyl free radicals are generated in the laboratory. Sonolysis and other studies, with curcumin or β -carotene in particular, provide stimulating, relatively inexpensive, and practical teaching excercises.

Organic chemists have long been familiar with the variety of addition and hydrogen transfer reactions that thiyl free radicals (RS25CF) can undergo, and of the chain processes and relatively fast reversible reactions that can often take place.

The reactions of organic free radicals, acting as either reductants or oxidants, have been studied by pulse radiolysis in neutral aqueous solution at room temperature. Many hydroxyl-substituted aliphatic carbon-centred radicals and one-electron adducts have been shown to be good one-electron reductants, while several oxygen-, sulphurand nitrogen- (but not carbon-) centred free radicals have been shown to be good one-electron oxidants. Several carbon-centred radicals can be reduced rapidly by hydrogen transfer, from undissociated thiol compounds which can thus act as catalysts facilitating the overall reduction of a carbon-centred radical by an electron-donating molecule. Kinetic considerations influenced by the one-electron redox potentials of the radical-molecule couples involved, determine whether a particular reaction predominates. In this paper examples of such reactions, involving a water-soluble derivative of vitamin E (Trolox C) and the coenzyme NADH, are described, together with studies showing ( a ) that even in complex multi-solute systems some organic peroxy radicals can inactiviate alcohol dehydrogenase under conditions where the superoxide radical does not, and ( b ) the superoxide radical can be damaging if urate is also present, and this damage can be reduced by the presence of superoxide dismutase.