[en] Mechanisms of particulate matter (PM)-induced cardiotoxicity are not fully understood. Direct translocation of PM-associated metals, including zinc, may mediate this effect. We hypothesized that following a single intratracheal instillation (IT), zinc directly translocates outside of the lungs, reaching the heart. To test this, we used high resolution magnetic sector field inductively coupled plasma mass spectrometry to measure levels of five stable isotopes of zinc (⁶⁴Zn, ⁶⁶Zn, ⁶⁷Zn, ⁶⁸Zn, ⁷⁰Zn), and copper in lungs, plasma, heart, liver, spleen, and kidney of male Wistar Kyoto rats (13 weeks old, 250-300 g), 1, 4, 24, and 48 h following a single IT or oral gavage of saline or 0.7 μmol/rat ⁷⁰Zn, using a solution enriched with 76.6% ⁷⁰Zn. Natural abundance of ⁷⁰Zn is 0.62%, making it an easily detectable tracer following exposure. In IT rats, lung ⁷⁰Zn was highest 1 h post IT and declined by 48 h. Liver endogenous zinc was increased 24 and 48 h post IT. ⁷⁰Zn was detected in all extrapulmonary organs, with levels higher following IT than following gavage. Heart ⁷⁰Zn was highest 48 h post IT. Liver, spleen and kidney ⁷⁰Zn peaked 4 h following gavage, and 24 h following IT. ⁷⁰Zn IT exposure elicited changes in copper homeostasis in all tissues. IT instilled ⁷⁰Zn translocates from lungs into systemic circulation. Route of exposure affects ⁷⁰Zn translocation kinetics. Our data suggests that following pulmonary exposure, zinc accumulation and subsequent changes in normal metal homeostasis in the heart and other organs could induce cardiovascular injury

[en] The Open Science Grid (OSG) provides a distributed facility where the Consortium members provide guaranteed and opportunistic access to shared computing and storage resources. OSG provides support for and evolution of the infrastructure through activities that cover operations, security, software, troubleshooting, addition of new capabilities, and support for existing and engagement with new communities. The OSG SciDAC-2 project provides specific activities to manage and evolve the distributed infrastructure and support it's use. The innovative aspects of the project are the maintenance and performance of a collaborative (shared and common) petascale national facility over tens of autonomous computing sites, for many hundreds of users, transferring terabytes of data a day, executing tens of thousands of jobs a day, and providing robust and usable resources for scientific groups of all types and sizes. More information can be found at the OSG web site: www.opensciencegrid.org

[en] Engineered carbon nanotubes are being developed for a wide range of industrial and medical applications. Because of their unique properties, nanotubes can impose potentially toxic effects, particularly if they have been modified to express functionally reactive chemical groups on their surface. The present study was designed to evaluate whether acid functionalization (AF) enhanced the cardiopulmonary toxicity of single-walled carbon nanotubes (SWCNT) as well as control carbon black particles. Mice were exposed by oropharyngeal aspiration to 10 or 40 μg of saline-suspended single-walled carbon nanotubes (SWCNTs), acid-functionalized SWCNTs (AF-SWCNTs), ultrafine carbon black (UFCB), AF-UFCB, or 2 μg LPS. 24 hours later, pulmonary inflammatory responses and cardiac effects were assessed by bronchoalveolar lavage and isolated cardiac perfusion respectively, and compared to saline or LPS-instilled animals. Additional mice were assessed for histological changes in lung and heart. Instillation of 40 μg of AF-SWCNTs, UFCB and AF-UFCB increased percentage of pulmonary neutrophils. No significant effects were observed at the lower particle concentration. Sporadic clumps of particles from each treatment group were observed in the small airways and interstitial areas of the lungs according to particle dose. Patches of cellular infiltration and edema in both the small airways and in the interstitium were also observed in the high dose group. Isolated perfused hearts from mice exposed to 40 μg of AF-SWCNTs had significantly lower cardiac functional recovery, greater infarct size, and higher coronary flow rate than other particle-exposed animals and controls, and also exhibited signs of focal cardiac myofiber degeneration. No particles were detected in heart tissue under light microscopy. This study indicates that while acid functionalization increases the pulmonary toxicity of both UFCB and SWCNTs, this treatment caused cardiac effects only with the AF-carbon nanotubes. Further experiments are needed to understand the physico-chemical processes involved in this phenomenon.

[en] The Cleveland airshed comprises a complex mixture of industrial source emissions that contribute to periods of non-attainment for fine particulate matter (PM_2.5) and are associated with increased adverse health outcomes in the exposed population. Specific PM sources responsible for health effects however are not fully understood. Size-fractionated PM (coarse, fine, and ultrafine) samples were collected using a ChemVol sampler at an urban site (G.T. Craig (GTC)) and rural site (Chippewa Lake (CLM)) from July 2009 to June 2010, and then chemically analyzed. The resulting speciated PM data were apportioned by EPA positive matrix factorization to identify emission sources for each size fraction and location. For comparisons with the ChemVol results, PM samples were also collected with sequential dichotomous and passive samplers, and evaluated for source contributions to each sampling site. The ChemVol results showed that annual average concentrations of PM, elemental carbon, and inorganic elements in the coarse fraction at GTC were ∼2, ∼7, and ∼3 times higher than those at CLM, respectively, while the smaller size fractions at both sites showed similar annual average concentrations. Seasonal variations of secondary aerosols (e.g., high NO₃⁻ level in winter and high SO₄²⁻ level in summer) were observed at both sites. Source apportionment results demonstrated that the PM samples at GTC and CLM were enriched with local industrial sources (e.g., steel plant and coal-fired power plant) but their contributions were influenced by meteorological conditions and the emission source's operation conditions. Taken together the year-long PM collection and data analysis provides valuable insights into the characteristics and sources of PM impacting the Cleveland airshed in both the urban center and the rural upwind background locations. These data will be used to classify the PM samples for toxicology studies to determine which PM sources, species, and size fractions are of greatest health concern. - Highlights: • PM sources in the Cleveland airshed varied across regions and with seasons. • Local industrial source impacts in the urban site were higher than the rural site. • Local industrial sources were mostly emitted from steel and coal-fired power plants. • Local industrial source impacts were associated with meteorological conditions. - The Cleveland airshed was enriched with local industrial sources but their contributions were influenced by meteorological conditions and emission source operation conditions.

[en] Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Male Wistar Kyoto rats were instilled intratracheally with saline or zinc sulfate, 131 μg/kg (2 μmol/kg); the alterations were determined at 1, 4, 24, and 48 h postexposure. High-dose zinc enabled us to show changes in circulating levels of zinc above normal and induce significant pulmonary inflammation/injury such that cardiac impairments were likely. At 1-24 h postexposure, plasma levels of zinc increased to nearly 20% above the base line. Significant pulmonary inflammation and injury were determined by analysis of bronchoalveolar lavage fluid and histopathology in zinc-exposed rats at all time points. Starting at 4 h postexposure, pulmonary damage was accompanied by persistently increased gene expressions of tissue factor (TF) and plasminogen activator-inhibitor-1 (PAI-1), but not thrombomodulin (TM). Cardiac tissues demonstrated similar temporal increases in expressions of TF, PAI-1, and TM mRNA following pulmonary instillation of zinc. In contrast to extensive pulmonary edema and inflammation, only mild, and focal acute, myocardial lesions developed in a few zinc-exposed rats; no histological evidence showed increased deposition of fibrin or disappearance of troponin. At 24 and 48 h postexposure to zinc, increases occurred in levels of systemic fibrinogen and the activated partial thromboplastin time. These data suggest that cardiovascular blood coagulation impairments are likely following pulmonary zinc exposure and associated pulmonary injury and inflammation