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Variability in bioreactivity linked to changes in size and zeta potential of diesel exhaust particles in human immune cells.

Paul J. Lioy, Ph.D. - Fri, 08/01/2014 - 02:00

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Variability in bioreactivity linked to changes in size and zeta potential of diesel exhaust particles in human immune cells.

PLoS One. 2014;9(5):e97304

Authors: Sarkar S, Zhang L, Subramaniam P, Lee KB, Garfunkel E, Strickland PA, Mainelis G, Lioy PJ, Tetley TD, Chung KF, Zhang J, Ryan M, Porter A, Schwander S

Abstract
Acting as fuel combustion catalysts to increase fuel economy, cerium dioxide (ceria, CeO2) nanoparticles have been used in Europe as diesel fuel additives (Envirox™). We attempted to examine the effects of particles emitted from a diesel engine burning either diesel (diesel exhaust particles, DEP) or diesel doped with various concentrations of CeO2 (DEP-Env) on innate immune responses in THP-1 and primary human peripheral blood mononuclear cells (PBMC). Batches of DEP and DEP-Env were obtained on three separate occasions using identical collection and extraction protocols with the aim of determining the reproducibility of particles generated at different times. However, we observed significant differences in size and surface charge (zeta potential) of the DEP and DEP-Env across the three batches. We also observed that exposure of THP-1 cells and PBMC to identical concentrations of DEP and DEP-Env from the three batches resulted in statistically significant differences in bioreactivity as determined by IL-1β, TNF-α, IL-6, IFN-γ, and IL-12p40 mRNA (by qRT-PCR) and protein expression (by ELISPOT assays). Importantly, bioreactivity was noted in very tight ranges of DEP size (60 to 120 nm) and zeta potential (-37 to -41 mV). Thus, these physical properties of DEP and DEP-Env were found to be the primary determinants of the bioreactivity measured in this study. Our findings also point to the potential risk of over- or under- estimation of expected bioreactivity effects (and by inference of public health risks) from bulk DEP use without taking into account potential batch-to-batch variations in physical (and possibly chemical) properties.

PMID: 24825358 [PubMed - in process]

Categories: Publications from UCDPER Members

Structural changes in hair follicles and sebaceous glands of hairless mice following exposure to sulfur mustard.

Jeffrey D. Laskin, Ph.D. - Fri, 08/01/2014 - 02:00

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Structural changes in hair follicles and sebaceous glands of hairless mice following exposure to sulfur mustard.

Exp Mol Pathol. 2014 Jun;96(3):316-27

Authors: Joseph LB, Heck DE, Cervelli JA, Composto GM, Babin MC, Casillas RP, Sinko PJ, Gerecke DR, Laskin DL, Laskin JD

Abstract
Sulfur mustard (SM) is a bifunctional alkylating agent causing skin inflammation, edema and blistering. A hallmark of SM-induced toxicity is follicular and interfollicular epithelial damage. In the present studies we determined if SM-induced structural alterations in hair follicles and sebaceous glands were correlated with cell damage, inflammation and wound healing. The dorsal skin of hairless mice was treated with saturated SM vapor. One to seven days later, epithelial cell karyolysis within the hair root sheath, infundibulum and isthmus was apparent, along with reduced numbers of sebocytes. Increased numbers of utriculi, some with connections to the skin surface, and engorged dermal cysts were also evident. This was associated with marked changes in expression of markers of DNA damage (phospho-H2A.X), apoptosis (cleaved caspase-3), and wound healing (FGFR2 and galectin-3) throughout pilosebaceous units. Conversely, fatty acid synthase and galectin-3 were down-regulated in sebocytes after SM. Decreased numbers of hair follicles and increased numbers of inflammatory cells surrounding the utriculi and follicular cysts were noted within the wound 3-7 days post-SM exposure. Expression of phospho-H2A.X, cleaved caspase-3, FGFR2 and galectin-3 was decreased in dysplastic follicular epidermis. Fourteen days after SM, engorged follicular cysts which expressed galectin-3 were noted within hyperplastic epidermis. Galectin-3 was also expressed in basal keratinocytes and in the first few layers of suprabasal keratinocytes in neoepidermis formed during wound healing indicating that this lectin is important in the early stages of keratinocyte differentiation. These data indicate that hair follicles and sebaceous glands are targets for SM in the skin.

PMID: 24662110 [PubMed - indexed for MEDLINE]

Categories: Publications from UCDPER Members

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

PandemicFlu.gov - Thu, 07/31/2014 - 14:00

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

Categories: Government Agency News

Human Recombinant Cytochrome P450 Enzymes Display Distinct Hydrogen Peroxide Generating Activities During Substrate Independent NADPH Oxidase Reactions.

Jeffrey D. Laskin, Ph.D. - Tue, 07/29/2014 - 02:00

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Human Recombinant Cytochrome P450 Enzymes Display Distinct Hydrogen Peroxide Generating Activities During Substrate Independent NADPH Oxidase Reactions.

Toxicol Sci. 2014 Jul 24;

Authors: Mishin V, Heck DE, Laskin DL, Laskin JD

Abstract
Microsomal enzymes generate H2O2 in the presence of NADPH. In this reaction, referred to as "oxidase" activity, H2O2 is generated directly or indirectly via the formation of superoxide anion. In the presence of redox active transition metals, H2O2 can form highly toxic hydroxyl radicals and, depending on the "oxidase" activity of individual cytochrome P450 isoenzymes, this can compromise cellular functioning and contribute to tissue injury. In the present studies we compared the initial rates of H2O2 generating activity of microsomal preparations containing various human recombinant cytochromes P450s. In the absence of cytochrome P450's the human recombinant NADPH cytochrome P450 reductase (CPR) generated low, but detectable amounts of H2O2 (∼ 0.04 nmole H2O2/min/100 Units of reductase). Significantly greater activity was detected in preparations containing individual cytochrome P450s co-expressed with CPR (from 6.0 nmoles H2O2/min/nmole P450 to 0.2 nmole/min/nmole P450); CYP1A1 was the most active, followed by CYP2D6, CYP3A4, CYP2E1, CYP4A11, CYP1A2 and CYP2C subfamily enzymes. H2O2 generating activity of the cytochrome P450s was independent of the ratio of CYP/CPR. Thus, similar H2O2 generating activity was noted with the same cytochrome P450s (CYP3A4, CYP2E1 and CYP2C9) expressed at or near the ratio of CYP/CPR in human liver microsomes (5-7), and when CPR was present in excess (CYP/CPR = 0.2-0.3). Since CYP3A4/5/7 represent up to 40% of total cytochrome P450 in the liver, these data indicate that these enzymes are the major source of H2O2 in human liver microsomes.

PMID: 25061110 [PubMed - as supplied by publisher]

Categories: Publications from UCDPER Members

South Dakota Severe Storms, Tornadoes, and Flooding

FEMA Disaster Declarations - Mon, 07/28/2014 - 17:07

Major Disaster Declaration number 4186 issued Mon, 07/28/2014 - 17:30

Categories: Government Agency News

Nebraska Severe Storms, Tornadoes, Straight-line Winds, and Flooding

FEMA Disaster Declarations - Mon, 07/28/2014 - 11:07

Major Disaster Declaration number 4185 issued Mon, 07/28/2014 - 11:02

Categories: Government Agency News

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation.

Jeffrey D. Laskin, Ph.D. - Sat, 07/26/2014 - 02:00

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Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation.

Exp Mol Pathol. 2014 May 30;

Authors: Sunil VR, Vayas KN, Cervelli JA, Malaviya R, Hall L, Massa CB, Gow AJ, Laskin JD, Laskin DL

Abstract
Nitrogen mustard (NM) is a toxic alkylating agent that causes damage to the respiratory tract. Evidence suggests that macrophages and inflammatory mediators including tumor necrosis factor (TNF)α contribute to pulmonary injury. Pentoxifylline is a TNFα inhibitor known to suppress inflammation. In these studies, we analyzed the ability of pentoxifylline to mitigate NM-induced lung injury and inflammation. Exposure of male Wistar rats (250g; 8-10weeks) to NM (0.125mg/kg, i.t.) resulted in severe histolopathological changes in the lung within 3d of exposure, along with increases in bronchoalveolar lavage (BAL) cell number and protein, indicating inflammation and alveolar-epithelial barrier dysfunction. This was associated with increases in oxidative stress proteins including lipocalin (Lcn)2 and heme oxygenase (HO)-1 in the lung, along with pro-inflammatory/cytotoxic (COX-2(+) and MMP-9(+)), and anti-inflammatory/wound repair (CD163(+) and Gal-3(+)) macrophages. Treatment of rats with pentoxifylline (46.7mg/kg, i.p.) daily for 3d beginning 15min after NM significantly reduced NM-induced lung injury, inflammation, and oxidative stress, as measured histologically and by decreases in BAL cell and protein content, and levels of HO-1 and Lcn2. Macrophages expressing COX-2 and MMP-9 also decreased after pentoxifylline, while CD163(+) and Gal-3(+) macrophages increased. This was correlated with persistent upregulation of markers of wound repair including pro-surfactant protein-C and proliferating nuclear cell antigen by Type II cells. NM-induced lung injury and inflammation were associated with alterations in the elastic properties of the lung, however these were largely unaltered by pentoxifylline. These data suggest that pentoxifylline may be useful in treating acute lung injury, inflammation and oxidative stress induced by vesicants.

PMID: 24886962 [PubMed - as supplied by publisher]

Categories: Publications from UCDPER Members

Disaster Nutrition in the Great East Japan Earthquake Disaster

Environmental/Disaster News - Thu, 07/24/2014 - 19:00

Nutrition in Clinical Practice

Nebraska Severe Storms, Tornadoes, Straight-line Winds, and Flooding

FEMA Disaster Declarations - Thu, 07/24/2014 - 10:07

Major Disaster Declaration number 4183 issued Thu, 07/24/2014 - 10:45

Categories: Government Agency News

Iowa Severe Storms, Tornadoes, Straight-line Winds, and Flooding

FEMA Disaster Declarations - Thu, 07/24/2014 - 09:07

Major Disaster Declaration number 4184 issued Thu, 07/24/2014 - 09:48

Categories: Government Agency News