Toxicological effects of ambient fine (PM2.5-0.18) and ultrafine (PM0.18) particles in healthy and diseased 3D organo-typic mucocilary-phenotype models.

The knowledge of the underlying mechanisms by which particulate matter (PM) exerts its health effects is still incomplete since it may trigger various symptoms as some persons may be more susceptible than others. Detailed studies realized in more relevant in vitro models are highly needed. Healthy normal human bronchial epithelial (NHBE), asthma-diseased human bronchial epithelial (DHBE), and COPD-DHBE cells, differentiated at the air-liquid interface, were acutely or repeatedly exposed to fine (i.e., PM2.5-0.18, also called FP) and quasi-ultrafine (i.e., PM0.18, also called UFP) particles. Immunofluorescence labelling of pan-cytokeratin, MUC5AC, and ZO-1 confirmed their specific cell-types. Baselines of the inflammatory mediators secreted by all the cells were quite similar. Slight changes of TNFα, IL-1ß, IL-6, IL-8, GM-CSF, MCP-1, and/or TGFα, and of H3K9 histone acetylation supported a higher inflammatory response of asthma- and especially COPD-DHBE cells, after exposure to FP and especially UFP. At baseline, 35 differentially expressed genes (DEG) in asthma-DHBE, and 23 DEG in COPD-DHBE, compared to NHBE cells, were reported. They were involved in biological processes implicated in the development of asthma and COPD diseases, such as cellular process (e.g., PLA2G4C, NLRP1, S100A5, MUC1), biological regulation (e.g., CCNE1), developmental process (e.g., WNT10B), and cell component organization and synthesis (e.g., KRT34, COL6A1, COL6A2). In all the FP or UFP-exposed cell models, DEG were also functionally annotated to the chemical metabolic process (e.g., CYP1A1, CYP1B1, CYP1A2) and inflammatory response (e.g., EREG). Another DEG, FGF-1, was only down-regulated in asthma and specially COPD-DHBE cells repeatedly exposed. While RAB37 could help to counteract the down-regulation of FGF-1 in asthma-DHBE cells, the deregulation of FGR, WNT7B, VIPR1, and PPARGC1A could dramatically contribute to make it worse in COPD-DHBE cells. Taken together, these data contributed to support the highest effects of UFP versus FP and highest sensitivity of asthma- and notably COPD-DHBE versus NHBE cells.

Genetic and epigenetic alterations in normal and sensitive COPD-diseased human bronchial epithelial cells repeatedly exposed to air pollution-derived PM2.5.

Even though clinical, epidemiological and toxicological studies have progressively provided a better knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects, further in vitro studies on relevant cell systems are still needed. Hence, aiming of getting closer to the human in vivo conditions, primary human bronchial epithelial cells derived from normal subjects (NHBE) or sensitive chronic obstructive pulmonary disease (COPD)-diseased patients (DHBE) were differentiated at the air-liquid interface. Thereafter, they were repeatedly exposed to air pollution-derived PM2.5 to study the occurrence of some relevant genetic and/or epigenetic endpoints. Concentration-, exposure- and season-dependent increases of OH-B[a]P metabolites in NHBE, and to a lesser extent, COPD-DHBE cells were reported; however, there were more tetra-OH-B[a]P and 8-OHdG DNA adducts in COPD-DHBE cells. No increase in primary DNA strand break nor chromosomal aberration was observed in repeatedly exposed cells. Telomere length and telomerase activity were modified in a concentration- and exposure-dependent manner in NHBE and particularly COPD-DHBE cells. There were a global DNA hypomethylation, a P16 gene promoter hypermethylation, and a decreasing DNA methyltransferase activity in NHBE and notably COPD-DHBE cells repeatedly exposed. Changes in site-specific methylation, acetylation, and phosphorylation of histone H3 (i.e., H3K4me3, H3K9ac, H3K27ac, and H3S10ph) and related enzyme activities occurred in a concentration- and exposure-dependent manner in all the repeatedly exposed cells. Collectively, these results highlighted the key role played by genetic and even epigenetic events in NHBE and particularly sensitive COPD-DHBE cells repeatedly exposed to air pollution-derived PM2.5 and their different responsiveness. While these specific epigenetic changes have been already described in COPD and even lung cancer phenotypes, our findings supported that, together with genetic events, these epigenetic events could dramatically contribute to the shift from healthy to diseased phenotypes following repeated exposure to relatively low doses of air pollution-derived PM2.5.

Fine particles sampled at an urban background site and an industrialized coastal site in Northern France - Part 1: Seasonal variations and chemical characterization.

The chemical composition of particulate matter sampled at two French Northern sites (Douai, DO - urban background; Grande-Synthe, GS - industrialized coastal site) was investigated during two summer and winter field campaigns at each site. Measurements of the major chemical species (organic, sulfate, nitrate, ammonium, chloride) in the non-refractory submicron aerosols (NR-PM1) were carried out by a High Resolution Time-of-Flight Aerosol Mass Spectrometer. Black Carbon in PM2.5 was monitored using an Aethalometer, while the OC and EC fractions and some targeted chemical organic families (polycyclic aromatic hydrocarbons, PAHs; dicarboxylic acids, DCAs) were quantified by the simultaneous collection of PM2.5 on filters followed by offline analyses. The seasonal trends and winter-to-summer (W/S) concentration ratios are discussed in this paper. Results indicate that the total average mass concentrations of PM2.5 varied between 20.5µgm-3 and 32.6µgm-3 in DO and between 10.6µgm-3 and 29.9µgm-3 in GS during summer and winter, respectively. Similar concentration patterns were found for PAHs and Organic Carbon (OC, representing ~80% of the total carbon) with highest concentrations in winter at the urban site. DCA concentrations showed less seasonal variations, although the highest value also appeared during winter. Total NR-PM1 presented concentrations in summer lower by a factor of 4 (for DO) and 10 (for GS) than those observed in winter. Organics and nitrates dominated the NR-PM1 in DO for both seasons and during winter in GS while sulfates and nitrates were the most dominant species in summer in GS. Average chloride concentrations were slightly more important in GS than those in DO related to its use in industrial processes and no significant seasonal trend was observed. The size-resolved chemical composition showed that aerosols sampled in DO in winter are more aged than those collected in GS where fresh emissions of sulfate from the industrial sector were observed.

[Postpartum perineal rehabilitation by early electrostimulation at home. Preliminary study]. / Rééducation périnéale du post-partum par électrostimulation précoce à domicile. Etude préliminaire.

The authors report a preliminary trial of post-partum perineal physiotherapy by functional electric stimulation at home starting from Day 15. Fifteen primipara used the technique. Perineal muscle testing and urodynamic investigations took place before Perineal muscle testing and urodynamic investigations took place before and after physiotherapy. Testing of the levators showed complete recovery in 20 p. cent of cases and partial in 80 p. cent. Urodynamic results showed a significant increase in resting urethral pressure. Acceptability of physiotherapy was perfect. The early start offered the twin advantages of better muscular recovery and easier motivation of the patient. Physiotherapy at home enabled these women, already busy, to carry out their perineal physiotherapy with minimum difficulty.