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

PandemicFlu.gov - 1 hour 39 min ago

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

Categories: Government Agency News

Evaluation of Diesel Exhaust Continuous Monitors in Controlled Environmental Conditions.

Paul J. Lioy, Ph.D. - 13 hours 39 min ago

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Evaluation of Diesel Exhaust Continuous Monitors in Controlled Environmental Conditions.

J Occup Environ Hyg. 2015 Apr 20;:0

Authors: Yu CH, Patton AP, Zhang A, Fan ZH, Weisel CP, Lioy PJ

Abstract
Diesel exhaust (DE) contains a variety of toxic air pollutants, including diesel particulate matter (DPM) and gaseous contaminants (e.g., carbon monoxide (CO)). DPM is dominated by fine (PM2.5) and ultrafine particles (UFP), and can be representatively determined by its thermal-optical refractory as elemental carbon (EC) or light-absorbing characteristics as black carbon (BC). The currently accepted reference method for sampling and analysis of occupational exposure to DPM is the National Institute for Occupational Safety and Health (NIOSH) Method 5040. However, this method cannot provide in-situ short-term measurements of DPM. Thus, real-time monitors are gaining attention to better examine DE exposures in occupational settings. However, real-time monitors are subject to changing environmental conditions. Field measurements have reported interferences in optical sensors and subsequent real-time readings, under conditions of high humidity and abrupt temperature changes. To begin dealing with these issues, we completed a controlled study to evaluate five real-time monitors: Airtec real-time DPM/EC Monitor, TSI SidePak Personal Aerosol Monitor AM510 (PM2.5), TSI Condensation Particle Counter 3007, microAeth AE51 BC Aethalometer, and Langan T15n CO Measurer. Tests were conducted under different temperatures (55, 70, and 80 °F), relative humidity (10, 40, and 80%), and DPM concentrations (50 and 200 μg/m(3)) in a controlled exposure facility. The 2-hour averaged EC measurements from the Airtec instrument showed relatively good agreement with NIOSH Method 5040 (R(2)=0.84; slope=1.17±0.06; N=27) and reported ˜17% higher EC concentrations than the NIOSH reference method. Temperature, relative humidity, and DPM levels did not significantly affect relative differences in 2-hour averaged EC concentrations obtained by the Airtec instrument versus the NIOSH method (p<0.05). Multiple linear regression analyses, based on 1-min averaged data, suggested combined effects of up to 5% from relative humidity and temperature on real-time measurements. The overall deviations of these real-time monitors from the NIOSH method results were ≤20%. However, simultaneous monitoring of temperature and relative humidity is recommended in field investigations to understand and correct for environmental impacts on real-time monitoring data.

PMID: 25894766 [PubMed - as supplied by publisher]

Categories: Publications from UCDPER Members

Parametrial fat tissue from high fat diet-treated SKH-1 mice stimulates transformation of mouse epidermal JB6 cells.

Jeffrey D. Laskin, Ph.D. - 13 hours 39 min ago

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Parametrial fat tissue from high fat diet-treated SKH-1 mice stimulates transformation of mouse epidermal JB6 cells.

J Carcinog Mutagen. 2014 Jul 31;5(183):2157-2518

Authors: Bernard JJ, Lou YR, Peng QY, Li T, Vakil PR, Ding N, Laskin JD, Dong Z, Conney AH, Lu YP

Abstract
Our previous studies indicated that decreasing visceral adipose tissue by surgical removal of the parametrial fat pads inhibited UVB-induced carcinogenesis in SKH-1 mice fed a high fat diet (HFD), but not a low fat diet (LFD) indicating that the parametrial fat tissue from mice fed a HFD played a role in skin carcinogenesis.
OBJECTIVE: In the present study, we sought to investigate how a HFD may influence the intrinsic properties of the parametrial fat tissue to influence UVB-induced skin tumor formation.
METHODS AND RESULTS: Immunohistochemical staining, adipokine array, and flow cytometry showed that parametrial fat tissue from mice fed a HFD had a higher density of macrophage-fused dead adipocytes (crown-like structures), more adipokines, and stimulated the production of more reactive oxygen species compared with parametrial fat tissue from mice fed a LFD. These differences between parametrial fat tissue from mice fed a HFD and LFD were associated with their effect on the in vitro transformation of mouse epidermal JB6 cells. Our results indicated that fat tissue filtrate (an aqueous filtrate made from the parametrial fat pad) from mice fed a HFD enhanced the conversion of JB6 cells from an epithelial-like morphology to cells with a fibroblast-like morphology to a greater extent than fat tissue filtrate from mice fed a LFD. Studies indicated that the fibroblast-like cells had decreased levels of E-cadherin, increased levels of Twist as assayed by western blot. Fat tissue filtrate made from the parametrial fat tissue of mice fed a HFD had 160% more transforming activity than that from mice fed a LFD and formed malignant mesenchymal tumors in vivo.
CONCLUSION: These studies provide the first in vitro demonstration of a parametrial fat tissue-induced transformation of an epidermal cell.

PMID: 25821644 [PubMed - as supplied by publisher]

Categories: Publications from UCDPER Members

Sulfa drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase.

Jeffrey D. Laskin, Ph.D. - 13 hours 39 min ago

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Sulfa drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase.

J Pharmacol Exp Ther. 2015 Mar;352(3):529-40

Authors: Yang S, Jan YH, Mishin V, Richardson JR, Hossain MM, Heindel ND, Heck DE, Laskin DL, Laskin JD

Abstract
Sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), the precursor for tetrahydrobiopterin (BH4), a cofactor critical for nitric oxide biosynthesis and alkylglycerol and aromatic amino acid metabolism. SPR also mediates chemical redox cycling, catalyzing one-electron reduction of redox-active chemicals, including quinones and bipyridinium herbicides (e.g., menadione, 9,10-phenanthrenequinone, and diquat); rapid reaction of the reduced radicals with molecular oxygen generates reactive oxygen species (ROS). Using recombinant human SPR, sulfonamide- and sulfonylurea-based sulfa drugs were found to be potent noncompetitive inhibitors of both sepiapterin reduction and redox cycling. The most potent inhibitors of sepiapterin reduction (IC50s = 31-180 nM) were sulfasalazine, sulfathiazole, sulfapyridine, sulfamethoxazole, and chlorpropamide. Higher concentrations of the sulfa drugs (IC50s = 0.37-19.4 μM) were required to inhibit redox cycling, presumably because of distinct mechanisms of sepiapterin reduction and redox cycling. In PC12 cells, which generate catecholamine and monoamine neurotransmitters via BH4-dependent amino acid hydroxylases, sulfa drugs inhibited both BH2/BH4 biosynthesis and redox cycling mediated by SPR. Inhibition of BH2/BH4 resulted in decreased production of dopamine and dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxytryptamine. Sulfathiazole (200 μM) markedly suppressed neurotransmitter production, an effect reversed by BH4. These data suggest that SPR and BH4-dependent enzymes, are "off-targets" of sulfa drugs, which may underlie their untoward effects. The ability of the sulfa drugs to inhibit redox cycling may ameliorate ROS-mediated toxicity generated by redox active drugs and chemicals, contributing to their anti-inflammatory activity.

PMID: 25550200 [PubMed - indexed for MEDLINE]

Categories: Publications from UCDPER Members

Modeling Population Exposures to Silver Nanoparticles Present in Consumer Products.

Paul J. Lioy, Ph.D. - Wed, 04/22/2015 - 02:00

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Modeling Population Exposures to Silver Nanoparticles Present in Consumer Products.

J Nanopart Res. 2014 Nov;16(11)

Authors: Royce SG, Mukherjee D, Cai T, Xu SS, Alexander JA, Mi Z, Calderon L, Mainelis G, Lee K, Lioy PJ, Tetley TD, Chung KF, Zhang J, Georgopoulos PG

Abstract
Exposures of the general population to manufactured nanoparticles (MNPs) are expected to keep rising due to increasing use of MNPs in common consumer products (PEN 2014). The present study focuses on characterizing ambient and indoor population exposures to silver MNPs (nAg). For situations where detailed, case-specific exposure-related data are not available, as in the present study, a novel tiered modeling system, Prioritization/Ranking of Toxic Exposures with GIS (Geographic Information System) Extension (PRoTEGE), has been developed: it employs a product Life Cycle Analysis (LCA) approach coupled with basic human Life Stage Analysis (LSA) to characterize potential exposures to chemicals of current and emerging concern. The PRoTEGE system has been implemented for ambient and indoor environments, utilizing available MNP production, usage, and properties databases, along with laboratory measurements of potential personal exposures from consumer spray products containing nAg. Modeling of environmental and microenvironmental levels of MNPs employs Probabilistic Material Flow Analysis combined with product LCA to account for releases during manufacturing, transport, usage, disposal, etc. Human exposure and dose characterization further employs screening Microenvironmental Modeling and Intake Fraction methods combined with LSA for potentially exposed populations, to assess differences associated with gender, age, and demographics. Population distributions of intakes, estimated using the PRoTEGE framework, are consistent with published individual-based intake estimates, demonstrating that PRoTEGE is capable of capturing realistic exposure scenarios for the US population. Distributions of intakes are also used to calculate biologically-relevant population distributions of uptakes and target tissue doses through human airway dosimetry modeling that takes into account product MNP size distributions and age-relevant physiological parameters.

PMID: 25745354 [PubMed - as supplied by publisher]

Categories: Publications from UCDPER Members