Socioeconomic gradients of adverse birth outcomes and related maternal factors in rural and urban Alberta, Canada: a concentration index approach.

OBJECTIVE: Using a summary measure of health inequalities, this study evaluated the distribution of adverse birth outcomes (ABO) and related maternal risk factors across area-level socioeconomic status (SES) gradients in urban and rural Alberta, Canada. DESIGN: Cross-sectional study using a validated perinatal clinical registry and an area-level SES. SETTING: The study was conducted in Alberta, Canada. Data about ABO and related maternal risk factors were obtained from the Alberta Perinatal Health Program between 2006 and 2012. An area-level SES index derived from census data (2006) was linked to the postal code at delivery. PARTICIPANTS: Women (n=3 30 957) having singleton live births with gestational age ≥22 weeks. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated concentration indexes to assess inequalities across SES gradients in both rural and urban areas (CIdxR and CIdxU, respectively) for spontaneous preterm birth (PTB), small for gestational age (SGA), large for gestational age (LGA), gestational hypertension, gestational diabetes, smoking and substance use during pregnancy and pre-pregnancy weight >91 kg. RESULTS: The highest health inequalities disfavouring low SES groups were identified for substance abuse and smoking in rural areas (CIdxR-0.38 and -0.23, respectively). Medium inequalities were identified for LGA (CIdxR-0.08), pre-pregnancy weight >91 kg (CIdxR-0.07), substance use (CIdxU-0.15), smoking (CIdxU-0.14), gestational diabetes (CIdxU-0.10) and SGA (CIdxU-0.07). Low inequalities were identified for PTB (CIdxR-0.05; CIdxU-0.05) and gestational diabetes (CIdxR-0.04). Inequalities disfavouring high SES groups were identified for gestational hypertension (CIdxR+0.04), SGA (CIdxR+0.03) and LGA (CIdxU+0.03). CONCLUSIONS: ABO and related maternal risk factors were unequally distributed across the socioeconomic gradient in urban-rural settings, with the greatest concentrations in lower SES groups of rural areas. Future research is needed on underlying mechanisms driving SES gradients in perinatal health across the rural-urban spectrum.

Inhalation of concentrated PM2.5 from Mexico City acts as an adjuvant in a guinea pig model of allergic asthma.

Exposure to Particulate Matter (PM) could function as an adjuvant depending on the city of origin in mice allergic asthma models. Therefore, our aim was to determine whether inhalation of fine particles (PM2.5) from Mexico City could act as an adjuvant inducing allergic sensitization and/or worsening the asthmatic response in guinea pig, as a suitable model of human asthma. Experimental groups were Non-Sensitized (NS group), sensitized with Ovalbumin (OVA) plus Aluminum hydroxide (Al(OH)3) as adjuvant (S + Adj group), and sensitized (OVA) without adjuvant (S group). All the animals were exposed to Filtered Air (FA) or concentrated PM2.5 (5 h/daily/3 days), employing an aerosol concentrator system, PM2.5 composition was characterized. Lung function was evaluated by barometric plethysmography (Penh index). Inflammatory cells present in bronchoalveolar lavage were counted as well as OVA-specific IgG1 and IgE were determined by ELISA assay. Our results showed in sensitized animals without Al(OH)3, that the PM2.5 exposure (609 ± 12.73 µg/m3) acted as an adjuvant, triggering OVA-specific IgG1 and IgE concentration. Penh index increased ∼9-fold after OVA challenge in adjuvant-sensitized animals as well as in S + PM2.5 group (∼6-fold), meanwhile NS + FA and S + FA lacked response. S + Adj + PM2.5 group showed an increase significantly of eosinophils and neutrophils in bronchoalveolar lavage. PM2.5 composition was made up of inorganic elements and Polycyclic Aromatic Hydrocarbons, as well as endotoxins and ß-glucan, all these components could act as adjuvant. Our study demonstrated that acute inhalation of PM2.5 acted as an adjuvant, similar to the aluminum hydroxide effect, triggering allergic asthma in a guinea pig model. Furthermore, in sensitized animals with aluminum hydroxide an enhancing influence of PM2.5 exposure was observed as specific-hyperresponsiveness to OVA challenge (quickly response) and eosinophilic and neutrophilic airway inflammation. Fine particles from Mexico City is a complex mix, which play a significant role as adjuvant in allergic asthma.

Airborne particulate matter in vitro exposure induces cytoskeleton remodeling through activation of the ROCK-MYPT1-MLC pathway in A549 epithelial lung cells.

Airborne particulate matter with an aerodynamic diameter ≤10µm (PM10) is considered a risk factor for the development of lung cancer. Little is known about the cellular mechanisms by which PM10 is associated with cancer, but there is evidence that its exposure can lead to an acquired invasive phenotype, apoptosis evasion, inflammasome activation, and cytoskeleton remodeling in lung epithelial cells. Cytoskeleton remodeling occurs through actin stress fiber formation, which is partially regulated through ROCK kinase activation, we aimed to investigate if this protein was activated in response to PM10 exposure in A549 lung epithelial cells. Results showed that 10µg/cm2 of PM10 had no influence on cell viability but increased actin stress fibers, cytoplasmic ROCK expression, and phosphorylation of myosin phosphatase-targeting 1 (MYPT1) and myosin light chain (MLC) proteins, which are targeted by ROCK. The inhibition of ROCK prevented actin stress fiber formation and the phosphorylation of MYPT1 and MLC, suggesting that PM10 activated the ROCK-MYPT1-MLC pathway in lung epithelial cells. The activation of ROCK1 has been involved in the acquisition of malignant phenotypes, and its induction by PM10 exposure could contribute to the understanding of PM10 as a risk factor for cancer development through the mechanisms associated with invasive phenotype.

Atmospheric particulate matter (PM10) exposure-induced cell cycle arrest and apoptosis evasion through STAT3 activation via PKCζ and Src kinases in lung cells.

Atmospheric particulate matter with aerodynamic diameter ≤10 µm (PM10) is a risk factor for the development of lung cancer, but cellular pathways are not completely understood. STAT3 is a p21(Waf1/Cip1) transcription factor and is associated with proliferation and cell survival and is upregulated in lung cancer. PM10 exposure induces p21(Waf1/Cip1) expression, which could be related to STAT3 activation. The aims of this work were to investigate whether STAT3 was activated on lung epithelial cells after PM10 exposure and to determine whether or not STAT3 could have an impact on cell cycle distribution and cell survival. Our results showed that PM10 induced STAT3 activation through Src and PKCζ kinases, and it is partially responsible for the p21(Waf1/Cip1) induction that was also observed. Moreover, PM10 induced G1-G0 cell cycle arrest. The inhibition of STAT3 phosphorylation prevented cell cycle arrest and triggered apoptosis. These results suggest that PM10 exposure might activate a survival pathway related to STAT3 activation, similar to what has been described as part of the immune system and apoptosis evasion during tumor promotion and development.

Sampling and composition of airborne particulate matter (PM10) from two locations of Mexico City.

The PM10 airborne particulate matter with an aerodynamic diameter ≤10 µm is considered as a risk factor of various adverse health outcomes, including lung cancer. Here we described the sampling and composition of PM10 collected from an industrial zone (IZ), and a commercial zone (CZ) of Mexico City. The PM10 was collected with a high-volume sampler in the above mentioned locations and both types of PM10 sampled were characterized by the content of polycyclic aromatic hydrocarbons (PAHs), metals, and endotoxin. The endotoxin PM10 content from IZ and CZ displayed 138.4 UE/mg and 170.4 UE/mg of PM10, respectively.

Particulate matter (PM10) induces metalloprotease activity and invasion in airway epithelial cells.

Airborne particulate matter with an aerodynamic diameter ≤ 10 µm (PM10) is a risk factor for the development of lung diseases and cancer. The aim of this work was to identify alterations in airway epithelial (A549) cells induced by PM10 that could explain how subtoxic exposure (10 µg/cm(2)) promotes a more aggressive in vitro phenotype. Our results showed that cells exposed to PM10 from an industrial zone (IZ) and an urban commercial zone (CZ) induced an increase in protease activity and invasiveness; however, the cell mechanism is different, as only PM10 from CZ up-regulated the activity of metalloproteases MMP-2 and MMP-9 and disrupted E-cadherin/ß-catenin expression after 48 h of exposure. These in vitro findings are relevant in terms of the mechanism action of PM10 in lung epithelial cells, which could be helpful in understanding the pathogenesis of some human illness associated with highly polluted cities.

Induction of c-Jun by air particulate matter (PM10) of Mexico city: Participation of polycyclic aromatic hydrocarbons.

The carcinogenic potential of urban particulate matter (PM) has been partly attributed to polycyclic aromatic hydrocarbons (PAHs) content, which activates the aryl hydrocarbon receptor (AhR). Here we report the effect of PM with an aerodynamic size of 10 µm (PM10) on the induction of AhR pathway in A549 cells, evaluating its downstream targets CYP1B1, IL-6, IL-8 and c-Jun. Significant increases in CYP1B1 protein and enzyme activity; IL-6 and IL-8 secretion and c-Jun protein were found in response to PM10. The formation of PAH-DNA adducts was also detected. The involvement of AhR pathway was confirmed with Resveratrol as AhR antagonist, which reversed CYP1B1 and c-Jun induction. Nevertheless, in IL-6 and IL-8 secretion, the Resveratrol was ineffective, suggesting an effect independent of this pathway. Considering the role of c-Jun in oncogenesis, its induction by PM may be contributing to its carcinogenic potential through induction of AhR pathway by PAHs present in PM10.

Cytoplasmic p21(CIP1/WAF1), ERK1/2 activation, and cytoskeletal remodeling are associated with the senescence-like phenotype after airborne particulate matter (PM(10)) exposure in lung cells.

The exposure to particulate matter with a mean aerodynamic diameter ≤10 µm (PM10) from urban zones is considered to be a risk factor in the development of cancer. The aim of this work was to determine if PM10 exposure induces factors related to the acquisition of a neoplastic phenotype, such as cytoskeletal remodeling, changes in the subcellular localization of p21(CIP1/WAF1), an increase in ß-galactosidase activity and changes in cell cycle. To test our hypothesis, PM10 from an industrial zone (IZ) and a commercial zone (CZ) were collected, and human adenocarcinoma lung cell cultures (A549) were exposed to a sublethal PM10 concentration (10 µg/cm(2)) for 24 h and 48 h. The results showed that PM10 exposure induced an increase in F-actin stress fibers and caused the cytoplasmic stabilization of p21(CIP1/WAF1) via phosphorylation at Thr(145) and Ser(146) and the phosphorylation of ERK1/2 on Thr(202). Changes in the cell cycle or apoptosis were not observed, but an increase in ß-galactosidase activity was detected. The PM10 from CZ caused more dramatic effects in lung cells. We conclude that PM10 exposure induced cytoplasmic p21(CIP1/WAF1) retention, ERK1/2 activation, cytoskeleton remodeling and the acquisition of a senescence-like phenotype in lung cells. These alterations could have mechanistic implications regarding the carcinogenic potential of PM10.

Induction of IL-6 and inhibition of IL-8 secretion in the human airway cell line Calu-3 by urban particulate matter collected with a modified method of PM sampling.

Exposure to particulate matter (PM) induces inflammatory cytokines. In the present study, we evaluated the secretion of IL-6 and IL-8 by an airway cell line exposed to PM with a mean aerodynamic size equal to or less than 10 or 2.5 microm (PM10 and PM2.5, respectively) collected in Mexico City, using a modified high-volume sampling method avoiding the use of solvents or introducing membrane components into the samples. PM was collected on cellulose-nitrate (CN) membranes modified for collection on high-volume samplers. Composition of the particles was evaluated by particle-induced X-ray emission (PIXE) and scanning electron microscopy. The particles (10-160 microg/cm2) were tested on Calu-3 cells. Control cultures were exposed to LPS (10 ng/mL to 100 microg/mL) or silica (10-160 microg/cm2). IL-6 and IL-8 secretions were evaluated by ELISA. An average of 10 mg of PM was recovered form each cellulose-nitrate filter. No evidence of contamination from the filter was found. Cells exposed to PM10 presented an increase in the secretion of IL-6 (up to 400%), while IL-8 decreased (from 40% to levels below the detection limit). A similar but weaker effect was observed with PM2.5. In conclusion, our modified sampling method provides a large amount of urban PM free of membrane contamination. The urban particles induce a decrease in IL-8 secretion that contrasts with the LPS and silica effects. These results suggest that the regulation of IL-8 expression is different for urban particles (complex mixture containing combustion-related particles, soil and biologic components) than for biogenic compounds or pure mineral particles.

In vitro induction of abnormal anaphases by contaminating atmospheric dust from the city of Mexicali, Baja California, Mexico

Mexicali dust (MD) is a mixture of particles of potassium aluminum silicates (98 percent) and sodium dioxide (2 percent) that induces pulmonary damage under experimental conditions, and is capable of inducing in vitro chromosomal alterations in exposed lymphocytes. It has been proposed as an atmospheric contaminant with pathogenic potential. among the chromosomal alterations observed, numeric alterations were predominant. The present study was designed to evaluate the capacity of MD to induce anaphasic changes in the Balb c 3T3 cell line. Chrysotile asbestos was used as a positive control. MD was found to induce abnormal anaphases, and the percentage of abnormalities increased as the dose increased (27.41 percent with 20 mg/mL, 29.60 percent with 40 mg/mL and 37.10 percent with 80 mg/mL). Multipolar anaphases constituted the most frequent altertion (69.1 - 78.8 percent), followed by lagging chromosomes (18.2 -29.5 percent) and anaphasic bridges (1.51 - 5.9 percent). The anaphasic alterations induced by MD showed differences in comparison to those observed with asbestos, especially for anaphasic bridges (10.4 percent vs. 1.51 percent, p<0.05). The capacity of MD to induce alterations resported in the process of chromosomal disjunction could explain the numeric aberrations reported previously by the authors of this paper. Therefore, these data support that MD could act as a clastogenic agent

Alteraciones cromosómicas inducidas por el polvo casero de la ciudad de Mexicali, Baja California / Chromosomic alterations induced by domestic dust in the city of Mexicaly, Baja California

El polvo de Mexicali es una mezcla de partículas formada por aluminosilicatos de potasio (98 por ciento) y dióxido de silicio (2 por ciento) que tiene potencial patogénico. El presente estudio se encaminó a evaluar el potencial de este polvo para inducir aberraciones cromosómicas. Se utilizó hierro carbonilo y asbesto crisótilo como controles negativo y positivo, respectivamente. Se emplearon linfocitos humanos de sangre periférica como células blanco provenientes de ocho donadores (hombres de 25-40 años sin antecedentes de cáncer en la familia), tres para la realización de curvas dosis-respuesta y cinco para los ensayos de caracterización de rompimientos cromosómicos. Se encontró que los polvos inducen alteraciones numéricas, independientemente del polvo evaluado, y se observó una tendencia a incrementarse el número de alteraciones numéricas conforme aumentó la dosis. También se observó que a la dosis de 50 µ/mL el polvo de Mexicali indujo un mayor número de aberraciones estructurales (6-15 por ciento), por lo que ésta fue la dosis empleada para la caracterización de las alterciones estructurales por medio del método de bandas GTG. Dentro de los rompimientos que pudieron ser caracterizados se encontraron algunos asociados a sitios frágiles y a bandas en las que se sabe existen protooncogenes o genes supresores de tumor

Evaluación de la capacidad hemolítica in vitro de muestras de polvo casero de la Delegación Benito Juárez (D.F) / Evaluation of the in vitro hemolytic ability of house dust samples from the Delegación Benito Juárez (D.F.)

En el presente estudio se evaluó la capacidad hemolítica del polvo colectado en casas de la Delegación Benito Juárez (PBJ), de la Ciudad de México. Los resultados obtenidos muestran que el PBJ induce porcentajes de hemólisis similares a los presentados por el hierro carbonilo y el polvo de Tlalpan (controles negativos), siendo éstos muy inferiores a los observados para el polvo de Mexicali (control positivo). A diferentes pH tanto el PBJ como el polvo de Mexicali incrementan su capacidad hemolítica conforme se alcaliniza el medio. Los polvos fueron lavados con una mezcla de cloroformo etanol para eliminar compuestos orgánicos que evitaran la interacción con los eritrocitos. Los resultados observados con las partículas lavadas fue muy similar al observado para las partículas sin lavar. El PBJ no indujo hemólisis in vitro, bajo ninguna de las condiciones evaluadas. Es necesario realizar estudios in vivo e in vitro que complementen al presente

Inducción de anafases anormales por polvos inorgánicos en cultivo de celulas BALBC/3T3 / Induction of abnormal anaphases by inorganic dusts in culture of BALBC/3T3 cells

Los polvos inorgánicos como el asbesto son capaces de inducir alteraciones cromosómicas in vitro. Estas alteraciones se han comprobado empleando fibras de longitud mayores de 5 µm. En el presente estudio se valoraron las anafases anormales inducidas por fibras de asbesto crisótilo y por hierro carbonilo con un tamaño menor de 5.0 µm. Se sembraron 10 células BALBC/3T3 en medio RPMI-1640 y se expusieron a las siguientes dosis de cada polvo: 0, 5, 10, 20, 40, 80 µg/ml durante 12 horas. Las células se fijaron y tiñeron con safranina-O para valorar las anafases anormales inducidas. Se observó que el asbesto crisótilo fue capaz de disminuir las anafases totales conforme de dosis de éste se elevó (de 36 por ciento a 8 por ciento), y el número máximo de anafases anormales fue de 5.6 por ciento con 40 µg/ml. A esta dosis, las anormalidades más comunes fueron los puentes anafásicos (4.3 por ciento) y las anafases multipolares (1.6 por ciento). El hierro carbolino no indujo disminución de las anafases y las anormales inducidas no fueron estadísticamente diferentes de las observadas en cultivos control. De nuestros resultados podemos concluir que las fibras de asbesto crisótilo menores de 5 µm de longitud inducen daño cromosómico directo e indirecto en cultivo celular

Generación de factores quimiotácticos para macrófagos alveolares, después de la instilación con asbesto crisotilo / Generation of chemotactic factors for alveolar macrophages after chrysotile asbestos instillation

Los modelos experimentales de asbestosis han demostrado que la respuesta inflamatoria inicial está mediada por macrófagos alveolares (MA). Aunque la atracción y acumulación de MA vistos en nuestros modelos está fundamentalmente mediada por el complemento, se ha sugerido la participación de otros factores quimiotácticos no bien caracterizados. En este trabajo, buscamos la presencia de factores quimiotácticos en ratas instiladas con asbesto en forma aguda. Demostramos morfoñlógicamente que el depósito de fibras, la respuesta macrofágica y las lesiones inducidas, son equivalentes a lo reportado en modelos por inhalación. Evaluamos la actividad quimiotáctica en el lavado broncoalveolar (LBA) fraccionado de acuerdo a su peso molecular (PM), y la presencia de albúmina y complemento. Encontramos actividad quimiotáctica en las fracciones del LBA correspondientes a picos de alto y bajo PM. La actividad del primer pico se atribuyó al complemento. La actividad del segundo, aumentó conforme al tiempo de exposición y no parece estar relacionada con complemento. Para identificar otros factores quimiotácticos diferentesa complemento, determinamos la presencia de factor de necrosis tumoral (TNFÿ) y fibronectina (FN) en los LBA no fraccionados. No se detectaron diferencias en la cantidad de TNF presente en los diferentes grupos. Observamos un incremento en la concentración de FN en relación al tiempo de exposición. Aunque la presencia de fracciones de FN pudiera explicar parcialmente el fenómeno quimiotáctico observado con el pico de bajo úPM, no podemos descartar la participación de otros factores no identificados