Impact of geocoding methods on associations between long-term exposure to urban air pollution and lung function

Background: Errors in address geocodes may affect estimates of the effects of air pollution on health.Objective: We investigated the impact of four geocoding techniques on the association between urban air pollution estimated with a fine-scale (10 m × 10 m) dispersion model and lung function in adults.Methods: We measured forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) in 354 adult residents of Grenoble, France, who were participants in two well-characterized studies, the Epidemiological Study on the Genetics and Environment on Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Home addresses were geocoded using individual building matching as the reference approach and three spatial interpolation approaches. We used a dispersion model to estimate mean PM10 and nitrogen dioxide concentrations at each participant's address during the 12 months preceding their lung function measurements. Associations between exposures and lung function parameters were adjusted for individual confounders and same-day exposure to air pollutants. The geocoding techniques were compared with regard to geographical distances between coordinates, exposure estimates, and associations between the estimated exposures and health effects.Results: Median distances between coordinates estimated using the building matching and the three interpolation techniques were 26.4, 27.9, and 35.6 m. Compared with exposure estimates based on building matching, PM10 concentrations based on the three interpolation techniques tended to be overestimated. When building matching was used to estimate exposures, a one-interquartile range increase in PM10 (3.0 μg/m3) was associated with a 3.72-point decrease in FVC% predicted (95% CI: -0.56, -6.88) and a 3.86-point decrease in FEV1% predicted (95% CI: -0.14, -3.24). The magnitude of associations decreased when other geocoding approaches were used [e.g., for FVC% predicted -2.81 (95% CI: -0.26, -5.35) using NavTEQ or 2.08 (95% CI -4.63, 0.47, p = 0.11) using Google Maps].Conclusions: Our findings suggest that the choice of geocoding technique may influence estimated health effects when air pollution exposures are estimated using a fine-scale exposure model.Citation: Jacquemin B, Lepeule J, Boudier A, Arnould C, Benmerad M, Chappaz C, Ferran J, Kauffmann F, Morelli X, Pin I, Pison C, Rios I, Temam S, Künzli N, Slama R, Siroux V. 2013. Impact of geocoding methods on associations between long-term exposure to urban air pollution and lung function. Environ Health Perspect 121:1054-1060; http://dx.doi.org/10.1289/ehp.1206016

On sampling minimum energy path

International audienceSampling the Minimum Energy Path (MEP) between two minima of a system is often hindered by the presence of an energy barrier separating the two metastable states. As a consequence, direct sampling based on Molecular Dynamics or Markov Chain Monte Carlo methods becomes inefficient, the crossing of the energy barrier being associated to a rare event. Augmented sampling methods based on the definition of collective variables or reaction coordinates allow to circumvent this limitation at the price of an arbitrary choice of the dimensionality reduction algorithm.We couple the statistical sampling techniques, namely Metadynamics and Invertible Neural Networks, with autoencoders so as to gradually learn the MEP and the collective variable at the same time. Learning is achieved through a succession of two steps: statistical sampling of the most probable path between the two minima and re-definition of the collective variable from the updated data points. The prototypical Mueller potential with nearly orthogonal minima is employed to demonstrate the ability of such coupling to unravel a complex MEP

Glutathione: Antioxidant Properties Dedicated to Nanotechnologies

International audienceWhich scientist has never heard of glutathione (GSH)? This well-known low-molecular-weight tripeptide is perhaps the most famous natural antioxidant. However, the interest in GSH should not be restricted to its redox properties. This multidisciplinary review aims to bring out some lesser-known aspects of GSH, for example, as an emerging tool in nanotechnologies to achieve targeted drug delivery. After recalling the biochemistry of GSH, including its metabolism pathways and redox properties, its involvement in cellular redox homeostasis and signaling is described. Analytical methods for the dosage and localization of GSH or glutathiolated proteins are also covered. Finally, the various therapeutic strategies to replenish GSH stocks are discussed, in parallel with its use as an addressing molecule in drug delivery

Endothelial γ-glutamyltransferase contributes to the vasorelaxant effect of S-nitrosoglutathione in rat aorta.

S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide ((•)NO) plays an important role in vascular homeostasis. Breakdown of GSNO can be catalyzed by γ-glutamyltransferase (GGT). We investigated whether vascular GGT influences the vasorelaxant effect of GSNO in isolated rat aorta. Histochemical localization of GGT and measurement of its activity were performed by using chromogenic substrates in sections and in aorta homogenates, respectively. The role of GGT in GSNO metabolism was evaluated by measuring GSNO consumption rate (absorbance decay at 334 nm), (•)NO release was visualized and quantified with the fluorescent probe 4,5-diaminofluorescein diacetate. The vasorelaxant effect of GSNO was assayed using isolated rat aortic rings (in the presence or absence of endothelium). The role of GGT was assessed by stimulating enzyme activity with cosubstrate glycylglycine, as well as using two independent inhibitors, competitive serine borate complex and non-competitive acivicin. Specific GGT activity was histochemically localized in the endothelium. Consumption of GSNO and release of free (•)NO decreased and increased in presence of serine borate complex and glycylglycine, respectively. In vasorelaxation experiments with endothelium-intact aorta, the half maximal effective concentration of GSNO (EC50 = 3.2 ± 0.5.10(-7) M) increased in the presence of the two distinct GGT inhibitors, serine borate complex (1.6 ± 0.2.10(-6) M) and acivicin (8.3 ± 0.6.10(-7) M), while it decreased with glycylglycine (4.7 ± 0.9.10(-8) M). In endothelium-denuded aorta, EC(50) for GSNO alone increased to 2.3 ± 0.3.10(-6) M, with no change in the presence of serine borate complex. These data demonstrate the important role of endothelial GGT activity in mediating the vasorelaxant effect of GSNO in rat aorta under physiological conditions. Because therapeutic treatments based on GSNO are presently under development, this endothelium-dependent mechanism involved in the vascular effects of GSNO should be taken into account in a pharmacological perspective

First multi-reactive polysaccharide-based transurf to produce potentially biocompatible dextran-covered nanocapsules

International audienceA multi-reactive polysaccharide-based transurf (acting both as macro-Chain Transfer Agent and stabilizer) was used to confine RAFT polymerization of methyl methacrylate (MMA) at the oil/water (o/w) miniemulsion interface. Dithiobenzoate groups and hydrophobic aliphatic side chains were introduced onto dextran, conferring it both transfer agent properties and ability to stabilize direct miniemulsion of MMA in the presence of a biocompatible oil, used as co-stabilizer. Because of their amphiphilic character, transurfs were initially adsorbed at the (o/w) interface and their reactive sites mediated RAFT polymerization via the R-group approach. PMMA-grafted dextran glycopolymers were consequently produced at the o/w interface, thus leading to dextran coverage/PMMA shell/oily core nanocapsules (NCs) as evidenced by Cryo-TEM analyses. The influence of dextran-based transurf chemistry and oil amount on MMA RAFT polymerization control was investigated. Positive preliminary results on NCs cytotoxicity suggest the potential of these objects for biomedical applications

Effects of modulation of GGT activity on GSNO-mediated ^•NO production in aortic tissue.

<p>Panel A: ^•NO production from rat aortic rings exposed to GSNO (1 mM) or GSNO (1 mM) in the presence of SBC (20 mM), glycylglycine (20 mM) or L-NAME (300 µM). Data are means ± SEM of 4–7 experiments, * p<0.05 <i>versus</i> GSNO. Panels B, C, D: representative fluorescence micrographs (×20) of 10-µm sections of rat aortic rings loaded for 2 h with 4,5-diaminofluorescein diacetate (DAF-2 DA, 10 µM) showing ^•NO production following 15-min incubation with GSNO (1 mM, panel C) or GSNO in the presence of SBC (20 mM, panel D) or glycylglycine (20 mM, panel B). Scale bar, 50 µm. All pictures were captured under constant exposure time, gain and offset.</p

Influence of GGT activity on the vasorelaxant effect of GSNO.

<p>Concentration-dependent vasorelaxation response curves of GSNO (•), GSNO with glycylglycine (20 mM) (Δ), GSNO with acivicin (50 µM) (◊), GSNO with SBC (20 mM) (□), and GSNO with ODQ (5 µM) (○) in endothelium-intact (panel A) and endothelium-denuded (panel B) aortic rings. Panel C: pD2 values (panel C). Data are means ± SEM of 4–12 aortic rings per group. p values (2 ways ANOVA test): p_interaction <0.0001; p_endothelium <0.0001; p_modulator_{of GGT} <0.0001. * p<0.05 <i>versus</i> GSNO endothelium-intact; $ p<0.05 <i>versus</i> GSNO endothelium-denuded (post-hoc Bonferroni test). ** p<0.05 versus GSNO in endothelium-intact aortic rings (one way ANOVA test).</p

Specific GGT activity and GSH consumption rate in rat aorta homogenates.

<p>Specific activity of γ-glutamyltransferase (GGT) and consumption rate of GSH measured in rat aorta homogenates incubated in Tris buffer pH 7.4 with and without SBC (20 mM) or glycylglycine (20 mM). Data are means ± S.E.M. of 3 experiments. (*p<0.05 versus Control; ND^#: not detected – below limit of detection).</p

Effects of modulation of GGT activity on GSNO consumption in rat aorta homogenates.

<p>Consumption rates of GSNO measured in rat aorta homogenates incubated in Tris buffer pH 7.4 with and without SBC (20 mM) or glycylglycine (20 mM). Data are means ± SEM of 3 experiments, * p<0.05 <i>versus</i> substrate alone.</p