Particulate Matter Exposure Impairs Systemic Microvascular Endothelium-Dependent Dilation

Acute exposure to airborne pollutants, such as solid particulate matter (PM), increases the risk of cardiovascular dysfunction, but the mechanisms by which PM evokes systemic effects remain to be identified. The purpose of this study was to determine if pulmonary exposure to a PM surrogate, such as residual oil fly ash (ROFA), affects endothelium-dependent dilation in the systemic microcirculation. Rats were intratracheally instilled with ROFA at 0.1, 0.25, 1 or 2 mg/rat 24 hr before experimental measurements. Rats intratracheally instilled with saline or titanium dioxide (0.25 mg/rat) served as vehicle or particle control groups, respectively. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar dilator responses to the Ca(2+) ionophore A23187, administered by ejection via pressurized micropipette into the arteriolar lumen. We used analysis of bronchoalveolar lavage (BAL) samples to monitor identified pulmonary inflammation and damage. To determine if ROFA exposure affected arteriolar nitric oxide sensitivity, sodium nitroprusside was iontophoretically applied to arterioles of rats exposed to ROFA. In saline-treated rats, A23187 dilated arterioles up to 72 ± 7% of maximum. In ROFA- and TiO(2)-exposed rats, A23187-induced dilation was significantly attenuated. BAL fluid analysis revealed measurable pulmonary inflammation and damage after exposure to 1 and 2 mg ROFA (but not TiO(2) or < 1 mg ROFA), as evidenced by significantly higher polymorphonuclear leukocyte cell counts, enhanced BAL albumin levels, and increased lactate dehydrogenase activity in BAL fluid. The sensitivity of arteriolar smooth muscle to NO was similar in saline-treated and ROFA-exposed rats, suggesting that pulmonary exposure to ROFA affected endothelial rather than smooth muscle function. A significant increase in venular leukocyte adhesion and rolling was observed in ROFA-exposed rats, suggesting local inflammation at the systemic microvascular level. These results indicate that pulmonary PM exposure impairs systemic endothelium-dependent arteriolar dilation. Moreover, because rats exposed to < 1 mg ROFA or TiO(2) did not exhibit BAL signs of pulmonary damage or inflammation, it appears that PM exposure can impair systemic microvascular function independently of detectable pulmonary inflammation

Glucose Tolerance as Affected by Pregnancy, Lactation, and Dietary Chromium

Department of Nutritional Science

Systemic Microvascular Dysfunction and Inflammation after Pulmonary Particulate Matter Exposure

The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and cardiovascular dysfunction is well known, but the systemic mechanisms that drive this effect remain unclear. We have previously shown that acute pulmonary exposure to PM impairs or abolishes endothelium-dependent arteriolar dilation in the rat spinotrapezius muscle. The purpose of this study was to further characterize the effect of pulmonary PM exposure on systemic microvascular function and to identify local inflammatory events that may contribute to these effects. Rats were intratracheally instilled with residual oil fly ash (ROFA) or titanium dioxide at 0.1 or 0.25 mg/rat 24 hr before measurement of pulmonary and systemic microvascular responses. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar responses to intraluminal infusion of the Ca(2+) ionophore A23187 or iontophoretic abluminal application of the adrenergic agonist phenylephrine (PHE). Leukocyte rolling and adhesion were quantified in venules paired with the studied arterioles. Histologic techniques were used to assess pulmonary inflammation, characterize the adherence of leukocytes to systemic venules, verify the presence of myeloperoxidase (MPO) in the systemic microvascular wall, and quantify systemic microvascular oxidative stress. In the lungs of rats exposed to ROFA or TiO(2), changes in some bronchoalveolar lavage markers of inflammation were noted, but an indication of cellular damage was not found. In rats exposed to 0.1 mg ROFA, focal alveolitis was evident, particularly at sites of particle deposition. Exposure to either ROFA or TiO(2) caused a dose-dependent impairment of endothelium-dependent arteriolar dilation. However, exposure to these particles did not affect microvascular constriction in response to PHE. ROFA and TiO(2) exposure significantly increased leukocyte rolling and adhesion in paired venules, and these cells were positively identified as polymorphonuclear leukocytes (PMNLs). In ROFA- and TiO(2)-exposed rats, MPO was found in PMNLs adhering to the systemic microvascular wall. Evidence suggests that some of this MPO had been deposited in the microvascular wall. There was also evidence for oxidative stress in the microvascular wall. These results indicate that after PM exposure, the impairment of endothelium-dependent dilation in the systemic microcirculation coincides with PMNL adhesion, MPO deposition, and local oxidative stress. Collectively, these microvascular observations are consistent with events that contribute to the disruption of the control of peripheral resistance and/or cardiac dysfunction associated with PM exposure

Differentiation of chemical reaction activity of various carbon nanotubes using redox potential: Classification by physical and chemical structures

The present study systematically examined the kinetics of a hydroxyl radical scavenging reaction of various carbon nanotubes (CNTs) including double- walled and multi-walled carbon nanotubes (DWCNTs and MWCNTs), and carbon nano peapods (AuCl3@DWCNT). The theoretical model that we recently proposed based on the redox potential of CNTs was used to analyze the experimental results. The reaction kinetics for DWCNTs and thin MWCNTs agreed well with the theoretical model and was consistent with each other. On the other hand, thin and thick MWCNTs behaved differently, which was consistent with the theory. Additionally, surface morphology of CNTs substantially influenced the reaction kinetics, while the doped particles in the center hollow parts of CNTs (AuCl3@DWCNT) shifted the redox potential in a different direction. These findings make it possible to predict the chemical and biological reactivity of CNTs based on the structural and chemical nature and their influence on the redox potential. (C) 2015 Elsevier Ltd. All rights reserved.ArticleCARBON. 95:302-308 (2015)journal articl

Exploring discordant low amyloid beta and high neocortical tau positron emission tomography cases

Introduction: Neocortical 3R4R (3-repeat/4-repeat) tau aggregates are rarely observed in the absence of amyloid beta (Aβ). 18F-MK6240 binds specifically to the 3R4R form of tau that is characteristic of Alzheimer\u27s disease (AD). We report four cases with negative Aβ, but positive tau positron emission tomography (PET) findings. Methods: All Australian Imaging, Biomarkers and Lifestyle study of aging (AIBL) study participants with Aβ (18F-NAV4694) and tau (18F-MK6240) PET scans were included. Centiloid \u3c 25 defined negative Aβ PET (Aβ–). The presence of neocortical tau was defined quantitatively and visually. Results: Aβ– PET was observed in 276 participants. Four of these participants (one cognitively unimpaired [CU], two mild cognitive impairment [MCI], one AD) had tau tracer retention in a pattern consistent with Braak tau stages V to VI. Fluid biomarkers supported a diagnosis of AD. In silico analysis of APP, PSEN1, PSEN2, and MAPT genes did not identify relevant functional mutations. Discussion: Discordant cases were infrequent (1.4% of all Aβ– participants). In these cases, the Aβ PET ligand may not be detecting the Aβ that is present

‘The invention of counting: the statistical measurement of literacy in nineteenth-century England’

This article examines the invention of counting literacy on a national basis in nineteenth-century Britain. Through an analysis of Registrar Generals' reports, it describes how the early statisticians wrestled with the implications of their new-found capacity to describe a nation's communications skills in a single table and how they were unable to escape their model of a society of isolated individuals divided into the literate and illiterate. The continuing influence of this approach is traced in the recent report from the Organisation for Economic Co-operation and Development's (OECD) Programme for the International Assessment of Adult Competencies (PIACC)

Nanoparticle inhalation augments particle-dependent systemic microvascular dysfunction

<p>Abstract</p> <p>Background</p> <p>We have shown that pulmonary exposure to fine particulate matter (PM) impairs endothelium dependent dilation in systemic arterioles. Ultrafine PM has been suggested to be inherently more toxic by virtue of its increased surface area. The purpose of this study was to determine if ultrafine PM (or nanoparticle) inhalation produces greater microvascular dysfunction than fine PM. Rats were exposed to fine or ultrafine TiO₂aerosols (primary particle diameters of ~1 μm and ~21 nm, respectively) at concentrations which do not alter bronchoalveolar lavage markers of pulmonary inflammation or lung damage.</p> <p>Results</p> <p>By histopathologic evaluation, no significant inflammatory changes were seen in the lung. However, particle-containing macrophages were frequently seen in intimate contact with the alveolar wall. The spinotrapezius muscle was prepared for in vivo microscopy 24 hours after inhalation exposures. Intraluminal infusion of the Ca²⁺ionophore A23187 was used to evaluate endothelium-dependent arteriolar dilation. In control rats, A23187 infusion produced dose-dependent arteriolar dilations. In rats exposed to fine TiO₂, A23187 infusion elicited vasodilations that were blunted in proportion to pulmonary particle deposition. In rats exposed to ultrafine TiO₂, A23187 infusion produced arteriolar constrictions or significantly impaired vasodilator responses as compared to the responses observed in control rats or those exposed to a similar pulmonary load of fine particles.</p> <p>Conclusion</p> <p>These observations suggest that at equivalent pulmonary loads, as compared to fine TiO₂, ultrafine TiO₂inhalation produces greater remote microvascular dysfunction.</p