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1.
Artigo em Inglês | MEDLINE | ID: mdl-31628893

RESUMO

Asbestos (Mg-hydrosilicate; chrysotile) is known to cause pleural diseases, pulmonary fibrosis and lung cancers, via mechanisms strongly depending on diameter-length ratio and possibly metal content. A critical question is whether synthetic hydrosilicate nanotubes (NTs) of short length possess little toxic potential compared to chrysotile. Five Mg- and two NiNTs of different lengths were assessed for cytotoxicity and pro-inflammatory responses in THP-1 macrophages and human bronchial epithelial lung cells (HBEC3-KT), in comparison with chrysotile. NT lengths/diameters were characterized by TEM, surface areas by BET- and BJH analysis, and chemical composition by XRD. The different Mg- and NiNTs induced little cytotoxicity in both cell models, in contrast to chrysotile that induced marked cytotoxicity. The two longest synthetic MgNTs, with median lengths of 3 and 5 µm, induced increased levels of pro-inflammatory cytokines in THP-1 macrophages, but much less than chrysotile (median length 15 µm) and silica nanoparticles (Si10). The shortest NTs did not induce any increase in cytokines. In HBEC3-KT cells, all synthetic NTs induced no or only small changes in cytokine responses, in contrast to chrysotile and Si10. The synthetic NTs induced lower TGF-ß responses than chrysotile in both cell models. In conclusion, the pro-inflammatory responses were associated with the length of synthetic hydrosilicate NTs in THP-1 macrophages, but not in HBEC3-KT cells. Notably, the shortest NTs showed no or little pro-inflammatory activity or cytotoxicity in both cell models. Such a safety by design approach is important for development of new materials being candidates for various new products.

2.
Environ Health Perspect ; 127(8): 87001, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393792

RESUMO

BACKGROUND: Telomere length is a molecular marker of biological aging. OBJECTIVE: Here we investigated whether early-life exposure to residential air pollution was associated with leukocyte telomere length (LTL) at 8 y of age. METHODS: In a multicenter European birth cohort study, HELIX (Human Early Life Exposome) ([Formula: see text]), we estimated prenatal and 1-y childhood exposure to nitrogen dioxide ([Formula: see text]), particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]), and proximity to major roads. Average relative LTL was measured using quantitative real-time polymerase chain reaction (qPCR). Effect estimates of the association between LTL and prenatal, 1-y childhood air pollution, and proximity to major roads were calculated using multiple linear mixed models with a random cohort effect and adjusted for relevant covariates. RESULTS: LTL was inversely associated with prenatal and 1-y childhood [Formula: see text] and [Formula: see text] exposures levels. Each standard deviation (SD) increase in prenatal [Formula: see text] was associated with a [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) change in LTL. Prenatal [Formula: see text] was nonsignificantly associated with LTL ([Formula: see text] per SD increase; 95% CI: [Formula: see text], 0.6). For each SD increment in 1-y childhood [Formula: see text] and [Formula: see text] exposure, LTL shortened by [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) and [Formula: see text] (95% CI: [Formula: see text], 0.1), respectively. Each doubling in residential distance to nearest major road during childhood was associated with a 1.6% (95% CI: 0.02, 3.1) lengthening in LTL. CONCLUSION: Lower exposures to air pollution during pregnancy and childhood were associated with longer telomeres in European children at 8 y of age. These results suggest that reductions in traffic-related air pollution may promote molecular longevity, as exemplified by telomere length, from early life onward. https://doi.org/10.1289/EHP4148.

3.
Pharmacoepidemiol Drug Saf ; 28(10): 1336-1343, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407838

RESUMO

PURPOSE: The purpose of the present study was to assess the agreement between self-reported use of sleep medications and tranquilizers and dispensed hypnotics and anxiolytics. METHODS: Self-reported medication use was obtained from the population-based survey Health and Environment in Oslo (HELMILO) (2009-2010) (n = 13 019). Data on dispensed hypnotics and anxiolytics were obtained from the Norwegian Prescription Database (NorPD). As measures of validity, we calculated sensitivity and specificity using both self-reports and prescription records as the reference standard. Furthermore, we calculated Cohen's kappa. Current self-reported medication use was compared with prescription data in time windows of both 100 and 200 days preceding questionnaire completion. RESULTS: The highest sensitivity was observed for current sleep medication use in the 100-day time window (sensitivity = 0.76, 95% confidence interval [CI]: 0.74, 0.79) when using prescription records as the reference standard. Sensitivity was generally lower for tranquilizers compared with sleep medications. Cohen's kappa showed the highest agreement for the 200-day time window with substantial agreement for sleep medications (kappa = 0.64; 95% CI: 0.62, 0.67) and moderate agreement for tranquilizers (kappa = 0.45; 95% CI: 0.41, 0.48). CONCLUSIONS: The present study suggests moderate to substantial agreement between self-reported use of sleep medications and tranquilizers and dispensed drugs in a general adult population. The magnitude of agreement varied according to drug category and time window. Since self-reported and registry-based use of these drug classes does not match each other accurately, limitations of each data source should be considered when such medications are applied as the exposure or outcome in epidemiologic studies.

4.
Environ Res ; 174: 95-104, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055170

RESUMO

The human exposome affects child development and health later in life, but its personal external levels, variability, and correlations are largely unknown. We characterized the personal external exposome of pregnant women and children in eight European cities. Panel studies included 167 pregnant women and 183 children (aged 6-11 years). A personal exposure monitoring kit composed of smartphone, accelerometer, ultraviolet (UV) dosimeter, and two air pollution monitors were used to monitor physical activity (PA), fine particulate matter (PM2.5), black carbon, traffic-related noise, UV-B radiation, and natural outdoor environments (NOE). 77% of women performed the adult recommendation of ≥150 min/week of moderate to vigorous PA (MVPA), while only 3% of children achieved the childhood recommendation of ≥60 min/day MVPA. 11% of women and 17% of children were exposed to daily PM2.5 levels higher than recommended (≥25µg/m3). Mean exposure to noise ranged from Lden 51.1 dB in Kaunas to Lden 65.2 dB in Barcelona. 4% of women and 23% of children exceeded the recommended maximum of 2 Standard-Erythemal-Dose of UV-B at least once a week. 33% of women and 43% of children never reached the minimum NOE contact recommendation of ≥30 min/week. The variations in air and noise pollution exposure were dominated by between-city variability, while most of the variation observed for NOE contact and PA was between-participants. The correlations between all personal exposures ranged from very low to low (Rho < 0.30). The levels of personal external exposures in both pregnant women and children are above the health recommendations, and there is little correlation between the different exposures. The assessment of the personal external exposome is feasible but sampling requires from one day to more than one year depending on exposure due to high variability between and within cities and participants.

5.
Environ Health Perspect ; 127(4): 47007, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31009264

RESUMO

BACKGROUND: The exposome is defined as the totality of environmental exposures from conception onwards. It calls for providing a holistic view of environmental exposures and their effects on human health by evaluating multiple environmental exposures simultaneously during critical periods of life. OBJECTIVE: We evaluated the association of the urban exposome with birth weight. METHODS: We estimated exposure to the urban exposome, including the built environment, air pollution, road traffic noise, meteorology, natural space, and road traffic (corresponding to 24 environmental indicators and 60 exposures) for nearly 32,000 pregnant women from six European birth cohorts. To evaluate associations with either continuous birth weight or term low birth weight (TLBW) risk, we primarily relied on the Deletion-Substitution-Addition (DSA) algorithm, which is an extension of the stepwise variable selection method. Second, we used an exposure-by-exposure exposome-wide association studies (ExWAS) method accounting for multiple hypotheses testing to report associations not adjusted for coexposures. RESULTS: The most consistent statistically significant associations were observed between increasing green space exposure estimated as Normalized Difference Vegetation Index (NDVI) and increased birth weight and decreased TLBW risk. Furthermore, we observed statistically significant associations among presence of public bus line, land use Shannon's Evenness Index, and traffic density and birth weight in our DSA analysis. CONCLUSION: This investigation is the first large urban exposome study of birth weight that tests many environmental urban exposures. It confirmed previously reported associations for NDVI and generated new hypotheses for a number of built-environment exposures. https://doi.org/10.1289/EHP3971.

7.
Part Fibre Toxicol ; 15(1): 21, 2018 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-29751765

RESUMO

BACKGROUND: Exposure to traffic-derived particulate matter (PM), such as diesel exhaust particles (DEP), is a leading environmental cause of cardiovascular disease (CVD), and may contribute to endothelial dysfunction and development of atherosclerosis. It is still debated how DEP and other inhaled PM can contribute to CVD. However, organic chemicals (OC) adhered to the particle surface, are considered central to many of the biological effects. In the present study, we have explored the ability of OC from DEP to reach the endothelium and trigger pro-inflammatory reactions, a central step on the path to atherosclerosis. RESULTS: Exposure-relevant concentrations of DEP (0.12 µg/cm2) applied on the epithelial side of an alveolar 3D tri-culture, rapidly induced pro-inflammatory and aryl hydrocarbon receptor (AhR)-regulated genes in the basolateral endothelial cells. These effects seem to be due to soluble lipophilic constituents rather than particle translocation. Extractable organic material of DEP (DEP-EOM) was next fractionated with increasing polarity, chemically characterized, and examined for direct effects on pro-inflammatory and AhR-regulated genes in human microvascular endothelial (HMEC-1) cells and primary human endothelial cells (PHEC) from four healthy donors. Exposure-relevant concentrations of lipophilic DEP-EOM (0.15 µg/cm2) induced low to moderate increases in IL-1α, IL-1ß, COX2 and MMP-1 gene expression, and the MMP-1 secretion was increased. By contrast, the more polar EOM had negligible effects, even at higher concentrations. Use of pharmacological inhibitors indicated that AhR and protease-activated receptor-2 (PAR-2) were central in regulation of EOM-induced gene expression. Some effects also seemed to be attributed to redox-responses, at least at the highest exposure concentrations tested. Although the most lipophilic EOM, that contained the majority of PAHs and aliphatics, had the clearest low-concentration effects, there was no straight-forward link between chemical composition and biological effects. CONCLUSION: Lipophilic and semi-lipophilic chemicals seemed to detach from DEP, translocate through alveolar epithelial cells and trigger pro-inflammatory reactions in endothelial cells at exposure-relevant concentrations. These effects appeared to be triggered by AhR agonists, and involve PAR-2 signaling.


Assuntos
Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Nanopartículas/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Emissões de Veículos/toxicidade , Ciclo-Oxigenase 2/genética , Citocinas/genética , Células Endoteliais/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação , Metaloproteinase 1 da Matriz/genética , Microvasos/efeitos dos fármacos , Microvasos/imunologia , Microvasos/metabolismo , Nanopartículas/química , Hidrocarbonetos Policíclicos Aromáticos/química , Transdução de Sinais
8.
J Occup Med Toxicol ; 13: 6, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29441119

RESUMO

The WHO has ranked environmental hazardous exposures in the living and working environment among the top risk factors for chronic disease mortality. Worldwide, about 40 million people die each year from noncommunicable diseases (NCDs) including cancer, diabetes, and chronic cardiovascular, neurological and lung diseases. The exposure to ambient pollution in the living and working environment is exacerbated by individual susceptibilities and lifestyle-driven factors to produce complex and complicated NCD etiologies. Research addressing the links between environmental exposure and disease prevalence is key for prevention of the pandemic increase in NCD morbidity and mortality. However, the long latency, the chronic course of some diseases and the necessity to address cumulative exposures over very long periods does mean that it is often difficult to identify causal environmental exposures. EU-funded COST Action DiMoPEx is developing new concepts for a better understanding of health-environment (including gene-environment) interactions in the etiology of NCDs. The overarching idea is to teach and train scientists and physicians to learn how to include efficient and valid exposure assessments in their research and in their clinical practice in current and future cooperative projects. DiMoPEx partners have identified some of the emerging research needs, which include the lack of evidence-based exposure data and the need for human-equivalent animal models mirroring human lifespan and low-dose cumulative exposures. Utilizing an interdisciplinary approach incorporating seven working groups, DiMoPEx will focus on aspects of air pollution with particulate matter including dust and fibers and on exposure to low doses of solvents and sensitizing agents. Biomarkers of early exposure and their associated effects as indicators of disease-derived information will be tested and standardized within individual projects. Risks arising from some NCDs, like pneumoconioses, cancers and allergies, are predictable and preventable. Consequently, preventative action could lead to decreasing disease morbidity and mortality for many of the NCDs that are of major public concern. DiMoPEx plans to catalyze and stimulate interaction of scientists with policy-makers in attacking these exposure-related diseases.

9.
Artigo em Inglês | MEDLINE | ID: mdl-29360764

RESUMO

Several earlier studies have shown the presence of more dust and allergens in carpets compared with non-carpeted floors. At the same time, adverse effects of carpeted floors on perceived indoor air quality as well as worsening of symptoms in individuals with asthma and allergies were reported. Avoiding extensive carpet use in offices, schools, kindergartens and bedrooms has therefore been recommended by several health authorities. More recently, carpet producers have argued that former assessments were obsolete and that modern rugs are unproblematic, even for those with asthma and allergies. To investigate whether the recommendation to be cautious with the use of carpets is still valid, or whether there are new data supporting that carpet flooring do not present a problem for indoor air quality and health, we have reviewed the literature on this matter. We have not found updated peer reviewed evidence that carpeted floor is unproblematic for the indoor environment. On the contrary, also more recent data support that carpets may act as a repository for pollutants which may become resuspended upon activity in the carpeted area. Also, the use of carpets is still linked to perception of reduced indoor air quality as well as adverse health effects as previously reported. To our knowledge, there are no publications that report on deposition of pollutants and adverse health outcomes associated with modern rugs. However, due to the three-dimensional structure of carpets, any carpet will to some extent act like a sink. Thus, continued caution should still be exercised when considering the use of wall-to-wall carpeted floors in schools, kindergartens and offices, as well as in children's bedrooms unless special needs indicate that carpets are preferable.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Asma/etiologia , Pisos e Cobertura de Pisos , Alérgenos , Poeira , Humanos , Hipersensibilidade , Instituições Acadêmicas
10.
Environ Health ; 16(1): 110, 2017 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-29078795

RESUMO

BACKGROUND: Road traffic noise has been associated with adverse health effects including sleep disturbances. Use of sleep medication as an indicator of sleeping problems has rarely been explored in studies of the effects of traffic noise. Furthermore, using registry data on sleep medications provides an opportunity to study the effects of noise on sleep where attribution of sleep problems to noise is not possible. METHODS: We used questionnaire data from the population-based study Health and Environment in Oslo (HELMILO) (2009-10) (n = 13,019). Individual data on sleep medications was obtained from the Norwegian Prescription Database (NorPD). Noise levels (L night) were modeled for the most exposed façade of the building at each participant's home address. Logistic regression models adjusted for potential confounders were used to analyze the association between traffic noise and sleep medication use both for one whole year and for the summer season. The results were reported as changes in the effect estimate per 5 decibel (dB) increase in noise level. RESULTS: We observed no association between traffic noise and sleep medication use during one year [odds ratio (OR) = 1.00; 95% confidence interval (CI): 0.96, 1.04]. For sleep medication use in the summer season, there was a positive, however non-significant association (OR = 1.04; 95% CI: 0.99, 1.10). Among individuals sleeping with the bedroom window open, the association increased slightly and was borderline statistically significant (OR = 1.06; 95% CI: 1.00, 1.12). CONCLUSIONS: We found no evidence of an association between traffic noise and sleep medication use during one year. However, for the summer season, there was some suggestive evidence of an association. These findings indicate that season may play a role in the association between traffic noise and sleep, possibly because indoor traffic noise levels are likely to be higher during summer due to more frequent window opening. More studies are, however, necessary in order to confirm this.


Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Ruído dos Transportes , Transtornos do Sono-Vigília/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Monitoramento Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Razão de Chances , Sistema de Registros , Estações do Ano
11.
Environ Health Perspect ; 125(10): 106002, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-29017987

RESUMO

BACKGROUND: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in in vitro models. OBJECTIVES: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP. METHODS: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas. DISCUSSION: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously. CONCLUSION: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa. https://doi.org/10.1289/EHP424.


Assuntos
Poluentes Atmosféricos/análise , Exposição Ambiental/estatística & dados numéricos , Nanoestruturas/análise , Material Particulado/análise , Poluentes Atmosféricos/toxicidade , Exposição Ambiental/análise , Humanos , Nanoestruturas/toxicidade , Material Particulado/toxicidade
12.
Sleep ; 40(2)2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28364487

RESUMO

Study Objectives: The aims of the present study were to investigate how nighttime road traffic noise relates to self-reported symptoms of insomnia and sleep medication use. Methods: We used questionnaire data from the population-based study Health and Environment in Oslo (HELMILO) (2009-2010; n = 13019). The insomnia symptoms difficulties falling asleep, awakenings during the night, and waking up too early in the morning as well as self-reported sleep medication use were included as outcomes. Modeled noise levels (Lnight) were assigned to each participant's home address. For selecting covariates to the statistical model, we used a directed acyclic graph. The associations between noise and sleep were analyzed using logistic regression models. Results: After adjustment for potential confounders, we found an odds ratio (OR) of 1.05 (95% confidence interval [CI]: 1.01-1.09) for the association between traffic noise and difficulties falling asleep, in the total study population. For the association between traffic noise and awakenings during the night, the OR was 1.04 (95% CI: 1.00-1.08) and for waking up too early, the OR was 1.06 (95% CI: 1.02-1.11). The effect estimates are given per 5-dB increase in traffic noise level (Lnight). Self-reported sleep medication use was not statistically significantly associated with traffic noise exposure. Conclusions: In an adult population from Oslo, traffic noise was associated with difficulties falling asleep and waking up too early. These findings indicate that sleep quantity may be compromised for individuals living in areas highly exposed to nighttime traffic noise.


Assuntos
Escuridão , Meio Ambiente , Ruído dos Transportes/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipnóticos e Sedativos/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Noruega , Razão de Chances , Autorrelato , Sono , Medicamentos Indutores do Sono/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Inquéritos e Questionários
13.
Basic Clin Pharmacol Toxicol ; 121 Suppl 3: 55-62, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28001342

RESUMO

A number of biological responses may contribute to the carcinogenic effects of combustion-derived particulate matter (CPM). Here, we focus on mechanisms that trigger CPM-induced pro-inflammatory responses. Inflammation has both genotoxic and non-genotoxic implications and is considered to play a central role in development of various health outcome associated with CPM exposure, including cancer. Chronic, low-grade inflammation may cause DNA damage through a persistent increased level of reactive oxygen species (ROS) produced and released by activated immune cells. Moreover, a number of pro-inflammatory cytokines and chemokines display mitogenic, motogenic, morphogenic and/or angiogenic properties and may therefore contribute to tumour growth and metastasis. The key triggering events involved in activation of pro-inflammatory responses by CPM and soluble CPM components can be categorized into (i) formation of ROS and oxidative stress, (ii) interaction with the lipid layer of cellular membranes, (iii) activation of receptors, ion channels and transporters on the cell surface and (iv) interactions with intracellular molecular targets including receptors such as the aryl hydrocarbon receptor (AhR). In particular, we will elucidate the effects of diesel exhaust particles (DEP) using human lung epithelial cells as a model system.


Assuntos
Carcinogênese/induzido quimicamente , Inflamação/induzido quimicamente , Material Particulado/toxicidade , Emissões de Veículos/toxicidade , Membrana Celular/metabolismo , Dano ao DNA , Células Epiteliais/patologia , Humanos , Inflamação/complicações , Canais Iônicos/metabolismo , Pulmão/citologia , Pulmão/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Superfície Celular/metabolismo
14.
PLoS One ; 11(11): e0166440, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27855223

RESUMO

Few studies have examined particulate matter (PM) exposure from self-reported use of wood stoves and other indoor combustion sources in urban settings in developed countries. We measured concentrations of indoor PM < 2.5 microns (PM2.5) for one week with the MicroPEM™ nephelometer in 36 households in the greater Oslo, Norway metropolitan area. We examined indoor PM2.5 levels in relation to use of wood stoves and other combustion sources during a 7 day monitoring period using mixed effects linear models with adjustment for ambient PM2.5 levels. Mean hourly indoor PM2.5 concentrations were higher (p = 0.04) for the 14 homes with wood stove use (15.6 µg/m3) than for the 22 homes without (12.6 µg/m3). Moreover, mean hourly PM2.5 was higher (p = 0.001) for use of wood stoves made before 1997 (6 homes, 20.2 µg/m3), when wood stove emission limits were instituted in Norway, compared to newer wood stoves (8 homes, 11.9 µg/m3) which had mean hourly values similar to control homes. Increased PM2.5 levels during diary-reported burning of candles was detected independently of concomitant wood stove use. These results suggest that self-reported use of wood stoves, particularly older stoves, and other combustion sources, such as candles, are associated with indoor PM2.5 measurements in an urban population from a high income country.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Cidades , Culinária , Exposição Ambiental/análise , Material Particulado/análise , Autorrelato , Fumaça , Humanos , Modelos Lineares , Noruega , Fatores de Tempo
15.
Toxicol Lett ; 238(2): 72-82, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26160521

RESUMO

Adsorbed soluble organics seem to be the main drivers of inflammatory responses induced by diesel exhaust particles (DEP). The specific compounds contributing to this process and the cellular mechanisms behind DEP-induced inflammation are not well known. We have assessed pro-inflammatory effects of DEP and various soluble DEP fractions, in human bronchial epithelial cells (BEAS-2B). DEP increased the expression of interleukin (IL)-6 and CXCL8. Silencing of the aryl hydrocarbon receptor (AhR) by siRNA or pretreatment with AhR-antagonists did not attenuate DEP-induced IL-6 and CXCL8 responses. However, the halogenated aromatic hydrocarbon (HAH)-selective AhR antagonist CH223191 caused a considerable reduction in DEP-induced CYP1A1 expression indicating that this response may be due to dioxin or dioxin-like constituents in DEP. Knock-down of protease activated receptor (PAR)-2 attenuated IL-6 responses without affecting CXCL8. Antioxidants did not affect IL-6 expression after 4h DEP-exposure and only partly reduced CXCL8 expression. However, after 24h exposure antioxidant treatment partly suppressed IL-6 protein release and completely blocked CXCL8 release. Furthermore, a heptane-soluble (non-polar) extract of DEP induced both IL-6 and CXCL8 release, whereas a PBS-soluble (highly polar) extract induced only IL-6. Thus, pro-inflammatory responses in DEP-exposed epithelial cells appear to be the result of both reactive oxygen species and receptor signaling, mediated through combinatorial effects between both non-polar and polar constituents adhered to the particle surface.


Assuntos
Antioxidantes/farmacologia , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Receptor PAR-2/efeitos dos fármacos , Emissões de Veículos/toxicidade , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular , Citocromo P-450 CYP1A1/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Heptanos/química , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Metanol/química , Material Particulado/química , Interferência de RNA , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Solubilidade , Solventes/química , Fatores de Tempo , Receptor 3 Toll-Like/agonistas , Receptor 3 Toll-Like/metabolismo , Transfecção
16.
Biomolecules ; 5(3): 1399-440, 2015 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-26147224

RESUMO

Inflammation is considered to play a central role in a diverse range of disease outcomes associated with exposure to various types of inhalable particulates. The initial mechanisms through which particles trigger cellular responses leading to activation of inflammatory responses are crucial to clarify in order to understand what physico-chemical characteristics govern the inflammogenic activity of particulate matter and why some particles are more harmful than others. Recent research suggests that molecular triggering mechanisms involved in activation of proinflammatory genes and onset of inflammatory reactions by particles or soluble particle components can be categorized into direct formation of reactive oxygen species (ROS) with subsequent oxidative stress, interaction with the lipid layer of cellular membranes, activation of cell surface receptors, and direct interactions with intracellular molecular targets. The present review focuses on the immediate effects and responses in cells exposed to particles and central down-stream signaling mechanisms involved in regulation of proinflammatory genes, with special emphasis on the role of oxidant and non-oxidant triggering mechanisms. Importantly, ROS act as a central second-messenger in a variety of signaling pathways. Even non-oxidant mediated triggering mechanisms are therefore also likely to activate downstream redox-regulated events.


Assuntos
Oxidantes/metabolismo , Material Particulado/toxicidade , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/metabolismo , Animais , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/metabolismo , Membrana Mucosa/patologia , Material Particulado/metabolismo , Sistema Respiratório/patologia
17.
Int J Environ Res Public Health ; 12(3): 2837-69, 2015 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-25749320

RESUMO

Air pollution is an important environmental factor associated with health impacts in Europe and considerable resources are used to reduce exposure to air pollution through emission reductions. These reductions will have non-linear effects on exposure due, e.g., to interactions between climate and atmospheric chemistry. By using an integrated assessment model, we quantify the effect of changes in climate, emissions and population demography on exposure and health impacts in Europe. The sensitivity to the changes is assessed by investigating the differences between the decades 2000-2009, 2050-2059 and 2080-2089. We focus on the number of premature deaths related to atmospheric ozone, Secondary Inorganic Aerosols and primary PM. For the Nordic region we furthermore include a projection on how population exposure might develop due to changes in building stock with increased energy efficiency. Reductions in emissions cause a large significant decrease in mortality, while climate effects on chemistry and emissions only affects premature mortality by a few percent. Changes in population demography lead to a larger relative increase in chronic mortality than the relative increase in population. Finally, the projected changes in building stock and infiltration rates in the Nordic indicate that this factor may be very important for assessments of population exposure in the future.


Assuntos
Aerossóis/efeitos adversos , Mudança Climática , Materiais de Construção/efeitos adversos , Exposição Ambiental/efeitos adversos , Mortalidade Prematura , Ozônio/efeitos adversos , Material Particulado/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Clima , Europa (Continente) , Previsões , Humanos , Modelos Teóricos
18.
Environ Res ; 138: 144-53, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25710788

RESUMO

BACKGROUND: Noise has been found to be associated with endocrine changes and cardiovascular disease. Increased cortisol levels and chronic sleep problems due to noise may increase the risk of obesity. OBJECTIVES: We investigated the relationship between road traffic noise and obesity markers. Furthermore, we explored the modifying role of noise sensitivity, noise annoyance, and sleep disturbances. METHODS: We used data from a population-based study, HUBRO (N=15,085), and its follow-up study HELMILO (N=8410) conducted in Oslo, Norway. Measurements were used to define body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and these binary outcomes: BMI≥30kg/m(2), WC≥102cm (men)/88cm (women), and WHR≥0.90 (men)/0.85 (women). Modelled levels of road traffic noise (Lden) were assigned to each participant's home address. Linear and logistic regression models were used to examine the associations. RESULTS: The results indicated no significant associations between road traffic noise and obesity markers in the total populations. However, in highly noise sensitive women (n=1106) a 10dB increase in noise level was associated with a slope (=beta) of 1.02 (95% confidence interval (CI): 1.01, 1.03) for BMI, 1.01 (CI: 1.00, 1.02) for WC, and an odds ratio (OR) of 1.24 (CI: 1.01, 1.53) for WHR ≥0.85. The associations appeared weaker in highly noise sensitive men. We found no effect modification of noise annoyance or sleep disturbances. In a sub-population with bedroom facing a road, the associations increased in men (e.g. an OR of 1.25 (CI: 0.88, 1.78) for BMI ≥30kg/m(2)), but not in women. Among long-term residents the associations increased for BMI ≥30kg/m(2) (OR of 1.07 (CI: 0.93, 1.24) in men and 1.10 (CI: 0.97, 1.26) in women), but not for the other outcomes. CONCLUSION: In an adult urban Scandinavian population, road traffic noise was positively associated with obesity markers among highly noise sensitive women. The associations appeared stronger among men with bedroom facing a street, representing a population with more accurately assigned exposure.


Assuntos
Exposição Ambiental , Ruído dos Transportes/efeitos adversos , Obesidade/diagnóstico , Obesidade/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Obesidade/etiologia , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/etiologia , Transtornos do Sono-Vigília/etiologia , Circunferência da Cintura , Razão Cintura-Estatura
19.
Environ Health Perspect ; 123(6): 525-33, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25712504

RESUMO

BACKGROUND: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. OBJECTIVES: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. METHODS: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter (PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions ≤ 2.5 µm (PM2.5) and ≤ 10 µm (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. RESULTS: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200 ng/m3). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. CONCLUSIONS: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição Ambiental , Material Particulado/toxicidade , Europa (Continente) , Humanos , Tamanho da Partícula , Modelos de Riscos Proporcionais
20.
J Inflamm Res ; 7: 169-85, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25540590

RESUMO

Different toxic agents have a varying potential to induce the production of the proinflammatory chemokine, CXCL8 (interleukin [IL]-8), in lung cells. A critical question is which mechanisms determine the magnitude and persistence of the CXCL8 responses to different stimuli. To approach this, we compared the potential of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), and sodium fluoride (NaF) to induce CXCL8 responses in A549 cells, with emphasis on the importance of nuclear factor kappa B (NF-κB)- and mitogen-activated protein kinase (MAPK) signaling. Notably, TPA induced a greater release of CXCL8 than did NaF. Furthermore, TPA induced a strong, rapid, but transient upregulation of CXCL8 messenger (m)RNA, whereas NaF induced a weaker, more delayed, but persistent upregulation. With respect to signaling, TPA led to an early, strong, and relatively transient extracellular signal-regulated kinase (ERK)1/2 phosphorylation, and a less marked and even more transient phosphorylation of c-jun-N-terminal kinases (JNK1/2) and p38. In contrast, NaF elicited a lower, but relatively sustained increase in phosphorylation of ERK1/2, and a marked phosphorylation of p38 and JNK1/2, with the JNK1/2 response as most transient. Only ERK1/2 inhibition affected the TPA response, whereas inhibition of all the three MAPK cascades reduced NaF-induced CXCL8 release. TPA also induced an early, marked phosphorylation/translocation of p65 (NF-κB), whereas NaF induced slower, less pronounced effects on p65. The CXCL8 responses by TPA and NaF were reduced by p65-siRNA. In conclusion, all MAPK cascades were involved in NaF-induced CXCL8 release, whereas only ERK1/2 activation was involved in response to TPA. Furthermore, NF-κB activation appeared to be indispensable for CXCL8 induction. The early response, magnitude, and persistency of MAPK and NF-κB signaling seemed to be critical determinants for the potential to induce CXCL8. These findings underscore that a strong, rapid, and relatively transient activation of ERK1/2 in combination with NF-kB may be sufficient for a strong induction of CXCL8, which may exceed the effects of a more moderate ERK1/2 activation in combination with activation of p38, JNK1/2, and NF-κB.

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