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The World Health Organization (WHO) Recommends Vaccine Composition for the 2011-2012 Northern Hemisphere Influenza Season

PandemicFlu.gov - 15 hours 56 min ago

The World Health Organization (WHO) Recommends Vaccine Composition for the 2011-2012 Northern Hemisphere Influenza Season

Categories: Government Agency News

Regulation of ozone-induced lung inflammation and injury by the β-galactoside-binding lectin galectin-3.

Jeffrey D. Laskin, Ph.D. - Wed, 03/04/2015 - 15:00

Regulation of ozone-induced lung inflammation and injury by the β-galactoside-binding lectin galectin-3.

Toxicol Appl Pharmacol. 2015 Feb 25;

Authors: Sunil VR, Francis M, Vayas KN, Cervelli JA, Choi H, Laskin JD, Laskin DL

Abstract
Macrophages play a dual role in ozone toxicity, contributing to both pro- and anti-inflammatory processes. Galectin-3 (Gal-3) is a lectin known to regulate macrophage activity. Herein, we analyzed the role of Gal-3 in the response of lung macrophages to ozone. Bronchoalveolar lavage (BAL) and lung tissue were collected 24-72h after exposure (3h) of WT and Gal-3(-/-) mice to air or 0.8ppm ozone. In WT mice, ozone inhalation resulted in increased numbers of proinflammatory (Gal-3(+), iNOS(+)) and anti-inflammatory (MR-1(+)) macrophages in the lungs. While accumulation of iNOS(+) macrophages was attenuated in Gal-3(-/-) mice, increased numbers of enlarged MR-1(+) macrophages were noted. This correlated with increased numbers of macrophages in BAL. Flow cytometric analysis showed that these cells were CD11b(+) and consisted mainly (>97%) mature (F4/80(+)CD11c(+)) proinflammatory (Ly6G(-)Ly6C(hi)) and anti-inflammatory (Ly6G(-)Ly6C(lo)) macrophages. Increases in both macrophage subpopulations were observed following ozone inhalation. Loss of Gal-3 resulted in a decrease in Ly6C(hi) macrophages, with no effect on Ly6C(lo) macrophages. CD11b(+)Ly6G(+)Ly6C(+) granulocytic (G) and monocytic (M) myeloid derived suppressor cells (MDSC) were also identified in the lung after ozone. In Gal-3(-/-) mice, the response of G-MDSC to ozone was attenuated, while the response of M-MDSC was heightened. Changes in inflammatory cell populations in the lung of ozone treated Gal-3(-/-) mice were correlated with reduced tissue injury as measured by cytochrome b5 expression. These data demonstrate that Gal-3 plays a role in promoting proinflammatory macrophage accumulation and toxicity in the lung following ozone exposure.

PMID: 25724551 [PubMed - as supplied by publisher]

Categories: Publications from UCDPER Members

Quantitative assessment of inhalation exposure and deposited dose of aerosol from nanotechnology-based consumer sprays.

Paul J. Lioy, Ph.D. - Wed, 03/04/2015 - 15:00

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Quantitative assessment of inhalation exposure and deposited dose of aerosol from nanotechnology-based consumer sprays.

Environ Sci Nano. 2014 Apr;1(2):161-171

Authors: Nazarenko Y, Lioy PJ, Mainelis G

Abstract
This study provides a quantitative assessment of inhalation exposure and deposited aerosol dose in the 14 nm to 20 μm particle size range based on the aerosol measurements conducted during realistic usage simulation of five nanotechnology-based and five regular spray products matching the nano-products by purpose of application. The products were also examined using transmission electron microscopy. In seven out of ten sprays, the highest inhalation exposure was observed for the coarse (2.5-10 μm) particles while being minimal or below the detection limit for the remaining three sprays. Nanosized aerosol particles (14-100 nm) were released, which resulted in low but measurable inhalation exposures from all of the investigated consumer sprays. Eight out of ten products produced high total deposited aerosol doses on the order of 10(1)-10(3) ng kg(-1) bw per application, ~85-88% of which were in the head airways, only <10% in the alveolar region and <8% in the tracheobronchial region. One nano and one regular spray produced substantially lower total deposited doses (by 2-4 orders of magnitude less), only ~52-64% of which were in the head while ~29-40% in the alveolar region. The electron microscopy data showed nanosized objects in some products not labeled as nanotechnology-based and conversely did not find nano-objects in some nano-sprays. We found no correlation between nano-object presence and abundance as per the electron microscopy data and the determined inhalation exposures and deposited doses. The findings of this study and the reported quantitative exposure data will be valuable for the manufacturers of nanotechnology-based consumer sprays to minimize inhalation exposure from their products, as well as for the regulators focusing on protecting the public health.

PMID: 25621175 [PubMed - as supplied by publisher]

Categories: Publications from UCDPER Members

Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard.

Jeffrey D. Laskin, Ph.D. - Sat, 02/28/2015 - 15:00

Related Articles

Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard.

Toxicol Appl Pharmacol. 2014 Oct 15;280(2):236-44

Authors: Chang YC, Wang JD, Hahn RA, Gordon MK, Joseph LB, Heck DE, Heindel ND, Young SC, Sinko PJ, Casillas RP, Laskin JD, Laskin DL, Gerecke DR

Abstract
Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal-epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure.

PMID: 25127551 [PubMed - indexed for MEDLINE]

Categories: Publications from UCDPER Members