Assessment of diesel exhaust particulate exposure and surface characteristics in association with levels of oxidative stress biomarkers

Exposure to PM10 and PM2.5 (particulate matter with aerodynamic diameter smaller than 10 μm and 2.5 μm, respectively) is associated with a range of adverse health effects, including cancer, pulmonary and cardiovascular diseases. Surface characteristics (chemical reactivity, surface area) are considered of prime importance to understand the mechanisms which lead to harmful effects. A hypothetical mechanism to explain these adverse effects is the ability of components (organics, metal ions) adsorbed on these particles to generate Reactive Oxygen Species (ROS), and thereby to cause oxidative stress in biological systems (Donaldson et al., 2003). ROS can attack almost any cellular structure, like DNA or cellular membrane, leading to the formation of a wide variety of degradation products which can be used as a biomarker of oxidative stress. The aim of the present research project is to test whether there is a correlation between the exposure to Diesel Exhaust Particulate (DEP) and the oxidative stress status. For that purpose, a survey has been conducted in real occupational situations where workers were exposed to DEP (bus depots). Different exposure variables have been considered: - particulate number, size distribution and surface area (SMPS); - particulate mass - PM2.5 and PM4 (gravimetry); - elemental and organic carbon (coulometry); - total adsorbed heavy metals - iron, copper, manganese (atomic adsorption); - surface functional groups present on aerosols (Knudsen flow reactor). (Demirdjian et al., 2005). Several biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and several aldehydes) have been determined either in urine or serum of volunteers. Results obtained during the sampling campaign in several bus depots indicated that the occupational exposure to particulates in these places was rather low (40-50 μg/m3 for PM4). Size distributions indicated that particles are within the nanometric range. Surface characteristics of sampled particles varied strongly, depending on the bus depot. They were usually characterized by high carbonyl and low acidic sites content. Among the different biomarkers which have been analyzed within the framework of this study, mean levels of 8- hydroxy-2'-deoxyguanosine and several aldehydes (hexanal, heptanal, octanal, nonanal) increased during two consecutive days of exposure for non-smokers. In order to bring some insight into the relation between the particulate characteristics and the formation of ROS by-products, biomarkers levels will be discussed in relation with exposure variables.

Evaluation in vitro de la réactivité des particules fines et ultrafines : rapport scientifique final

Une des percées les plus importantes dans la recherche sur les nanoparticules (ambiantes et manufacturées) a été la reconnaissance de leur potentiel à générer un stress oxydatif au niveau cellulaire. Dans cette optique, la mesure du potentiel oxydant intrinsèque des particules pourrait présenter une première étape dans l'évaluation des dangers. Ce projet méthodologique avait pour but de caractériser le potentiel oxydant de différentes nanoparticules « modèles » (ambiantes et manufacturées) au moyen de trois tests acellulaires (Test DTT, Test DCFH, Test oxymétrique) et d'utiliser ces résultats pour proposer une méthode de « référence ». D'autre part, nous avons appliqué la méthode sélectionnée à deux cas (exposition d'ouvriers à des particules de combustion et évaluation du danger de différentes nanoparticules manufacturées) afin de déterminer quels sont les paramètres qui influencent la mesure. Les résultats obtenus indiquent que la préparation des suspensions joue un rôle dans la mesure de ce potentiel oxydant. La réactivité dépend de la concentration du surfactant et de la durée de sonication. D'autre part, l'ordre de réactivité est dépendant de la métrique utilisée (masse ou surface) pour exprimer les résultats. Parmi les trois tests considérés, le test DTT pourrait être le plus utile pour effectuer une évaluation initiale du danger potentiel de nanoparticules ambiantes ou manufacturées. Ce test pourrait être intégré dans une stratégie d'évaluation de la toxicité des nanoparticules. Le test DTT correspond bien un test intégratif. Pour des situations de travail dans lesquelles les particules de combustion sont majoritaires, les paramètres physico-chimiques qui corrèlent de manière significative avec la réactivité DTT sont la surface des particules, les concentrations de carbone organique, la somme des concentrations de quatre quinones et les concentrations de fer et cuivre. Un nombre plus faible de corrélations est observé dans des ateliers mécaniques, suggérant que d'autres composés non mesurés interviennent également dans cette réactivité. Concernant les nanoparticules carbonées manufacturées, les fonctions chimiques de surface corrélées avec la réactivité DTT sont des fonctions acides et des fonctions inconnues pouvant dismuter. D'autre part, la solubilité et la possibilité de former des complexes avec le DTT sur la surface des NP manufacturées influencent le résultat de réactivité.

The effect of non-medical factors on variations in the performance of colonoscopy among different health care settings

BACKGROUND: Previous published studies have shown significant variations in colonoscopy performance, even when medical factors are taken into account. This study aimed to examine the role of nonmedical factors (ie, embodied in health care system design) as possible contributors to variations in colonoscopy performance. METHODS: Patient data from a multicenter observational study conducted between 2000 and 2002 in 21 centers in 11 western countries were used. Variability was captured through 2 performance outcomes (diagnostic yield and colonoscopy withdrawal time), jointly studied as dependent variables, using a multilevel 2-equation system. RESULTS: Results showed that open-access systems and high-volume colonoscopy centers were independently associated with a higher likelihood of detecting significant lesions and longer withdrawal durations. Fee for service (FFS) payment was associated with shorter withdrawal durations, and so had an indirect negative impact on the diagnostic yield. Teaching centers exhibited lower detection rates and longer withdrawal times. CONCLUSIONS: Our results suggest that gatekeeping colonoscopy is likely to miss patients with significant lesions and that developing specialized colonoscopy units is important to improve performance. Results also suggest that FFS may result in a lower quality of care in colonoscopy practice and highlight the fact that longer withdrawal times do not necessarily indicate higher quality in teaching centers.

Interlaboratory comparison of size measurements on nanoparticles using nanoparticle tracking analysis (NTA)

One of the key challenges in the field of nanoparticle (NP) analysis is in producing reliable and reproducible characterisation data for nanomaterials. This study looks at the reproducibility using a relatively new, but rapidly adopted, technique, Nanoparticle Tracking Analysis (NTA) on a range of particle sizes and materials in several different media. It describes the protocol development and presents both the data and analysis of results obtained from 12 laboratories, mostly based in Europe, who are primarily QualityNano members. QualityNano is an EU FP7 funded Research Infrastructure that integrates 28 European analytical and experimental facilities in nanotechnology, medicine and natural sciences with the goal of developing and implementing best practice and quality in all aspects of nanosafety assessment. This study looks at both the development of the protocol and how this leads to highly reproducible results amongst participants. In this study, the parameter being measured is the modal particle size.

Characterization of surface functional groups present on laboratory-generated and ambient aerosol particles by means of heterogeneous titration reactions

A Knudsen flow reactor has been used to quantify surface functional groups on aerosols collected in the field. This technique is based on a heterogeneous titration reaction between a probe gas and a specific functional group on the particle surface. In the first part of this work, the reactivity of different probe gases on laboratory-generated aerosols (limonene SOA, Pb(NO3)2, Cd(NO3)2) and diesel reference soot (SRM 2975) has been studied. Five probe gases have been selected for the quantitative determination of important functional groups: N(CH3)3 (for the titration of acidic sites), NH2OH (for carbonyl functions), CF3COOH and HCl (for basic sites of different strength), and O3 (for oxidizable groups). The second part describes a field campaign that has been undertaken in several bus depots in Switzerland, where ambient fine and ultrafine particles were collected on suitable filters and quantitatively investigated using the Knudsen flow reactor. Results point to important differences in the surface reactivity of ambient particles, depending on the sampling site and season. The particle surface appears to be multi-functional, with the simultaneous presence of antagonistic functional groups which do not undergo internal chemical reactions, such as acid-base neutralization. Results also indicate that the surface of ambient particles was characterized by a high density of carbonyl functions (reactivity towards NH2OH probe in the range 0.26-6 formal molecular monolayers) and a low density of acidic sites (reactivity towards N(CH3)3 probe in the range 0.01-0.20 formal molecular monolayer). Kinetic parameters point to fast redox reactions (uptake coefficient ?0>10-3 for O3 probe) and slow acid-base reactions (?0<10-4 for N(CH3)3 probe) on the particle surface. [Authors]

The use of heterogeneous chemistry for the characterization of functional groups at the gas/particle interface of soot and TiO(2) nanoparticles

Six gases (N((CH3)3), NH2OH, CF3COOH, HCl, NO2, O3) were selected to probe the surface of seven combustion aerosol (amorphous carbon, flame soot) and three types of TiO2 nanoparticles using heterogeneous, that is gas-surface reactions. The gas uptake to saturation of the probes was measured under molecular flow conditions in a Knudsen flow reactor and expressed as a density of surface functional groups on a particular aerosol, namely acidic (carboxylic) and basic (conjugated oxides such as pyrones, N-heterocycles) sites, carbonyl (R1-C(O)-R2) and oxidizable (olefinic, -OH) groups. The limit of detection was generally well below 1% of a formal monolayer of adsorbed probe gas. With few exceptions most investigated aerosol samples interacted with all probe gases which points to the coexistence of different functional groups on the same aerosol surface such as acidic and basic groups. Generally, the carbonaceous particles displayed significant differences in surface group density: Printex 60 amorphous carbon had the lowest density of surface functional groups throughout, whereas Diesel soot recovered from a Diesel particulate filter had the largest. The presence of basic oxides on carbonaceous aerosol particles was inferred from the ratio of uptakes of CF3COOH and HCl owing to the larger stability of the acetate compared to the chloride counterion in the resulting pyrylium salt. Both soots generated from a rich and a lean hexane diffusion flame had a large density of oxidizable groups similar to amorphous carbon FS 101. TiO2 15 had the lowest density of functional groups among the three studied TiO2 nanoparticles for all probe gases despite the smallest size of its primary particles. The used technique enabled the measurement of the uptake probability of the probe gases on the various supported aerosol samples. The initial uptake probability, g0, of the probe gas onto the supported nanoparticles differed significantly among the various investigated aerosol samples but was roughly correlated with the density of surface groups, as expected. [Authors]

Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers.

BACKGROUND: Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species.METHODS: Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species.RESULTS: Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001).CONCLUSIONS: These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations.

Colorectal cancer detection: how well do appropriateness criteria perform?

Comment on: Hassan C, Di Giulio E, Pickhardt PJ, Zullo A, Laghi A, Kim DH, Iafrate F, Morini S. Cost effectiveness of colonoscopy, based on the appropriateness of an indication. Clin Gastroenterol Hepatol. 2008 Nov;6(11):1231-6.

Appropriateness of therapy for active Crohn's disease: results of a multidisciplinary international expert panel (EPACT II)

Introduction: The development of novel therapies and the increasing number of trials testing management strategies for luminal Crohn's disease (CD) have not filled all the gaps in our knowledge. Thus, in clinical practice, many decisions for CD patients need to be taken without high quality evidence. For this reason, a multidisciplinary European expert panel followed the RAND method to develop explicit criteria for the management of individual patients with active, steroid-dependent (ST-D) and steroid-refractory (ST-R) CD. Methods: Twelve international experts convened in Geneva, Switzerland in December 2007, to rate explicit clinical scenarios, corresponding to real daily practice, on a 9-point scale according to the literature evidence and their own expertise. Median ratings were stratified into three categories: appropriate (7-9), uncertain (4-6) and inappropriate (1-3). Results: Overall, panelists rated 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD. In anti-TNF naïve patients, budesonide and prednisone were found appropriate for mildmoderate CD, and infliximab (IFX) when those had previously failed or had not been tolerated. In patients with prior success with IFX, this drug with or without co-administration of a thiopurine analog was favored. Other anti-TNFs were appropriate in case of intolerance or resistance to IFX. High doses steroids, IFX or adalimumab were appropriate in severe active CD. Among 105 indications for ST-D or ST-R disease, the panel considered appropriate the thiopurine analogs, methotrexate, IFX, adalimumab and surgery for limited resection, depending on the outcome of prior therapies. Anti-TNFs were generally considered appropriate in ST-R. Conclusion: Steroids, including budesonide for mild-to-moderate CD, remain first-line therapies in active luminal CD. Anti-TNFs, in particular IFX with respect to the amount of available evidence, remain second-line for most indications. Thiopurine analogs are preferred to anti-TNFs when steroids are not appropriate, except when anti-TNFs were previously successful. These recommendations are available online (www.epact.ch). A prospective evaluation of these criteria in a large database in Switzerland in underway to validate these criteria.