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Event
Thu 9/19/2019 11:00AM - 12:00PM
EOH Journal Club
Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen EOH Journal Club
Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen
Thu 9/19/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Brandy Hill

Paper: Particle Depletion Does Not Remediate Acute Effects of Traffic-related Air Pollution and Allergen. A Randomized, Double-Blind Crossover Study

Authors: Denise J. Wooding, Min Hyung Ryu, Anke Huls, Andrew D. Lee, David T. S. Lin, Christopher F. Rider, Agnes C. Y. Yuen, and Chris Carlsten

Abstract:
Rationale: Diesel exhaust (DE), an established model of trafficrelated
air pollution, contributes significantly to the global burden of
asthma and may augment the effects of allergen inhalation. Newer
diesel particulate-filtering technologies may increaseNO2 emissions,
raising questions regarding their effectiveness in reducing harm from
associated engine output.

Objectives: To assess the effects of DE and allergen coexposure on
lung function, airway responsiveness, and circulating leukocytes, and
determine whether DE particle depletion remediates these effects.

Methods: In this randomized, double-blind crossover study, 14
allergen-sensitized participants (9 with airway hyperresponsiveness)
underwent inhaled allergen challenge after 2-hour exposures to DE,
particle-depleted DE (PDDE), or filtered air. The control condition
was inhaled saline after filtered air. Blood sampling and spirometry
were performed before and up to 48 hours after exposures. Airway
responsiveness was evaluated at 24 hours.

Measurements and Main Results: PDDE plus allergen
coexposure impaired lung function more than DE plus allergen,
particularly in those genetically at risk. DE plus allergen and PDDE
plus allergen each increased airway responsiveness in normally
responsive participants.DEplus allergen increased blood neutrophils
and was associated with persistent eosinophilia at 48 hours. DE and
PDDE each increased total peripheral leukocyte counts in a manner
affected by participant genotypes. Changes in peripheral leukocytes
correlated with lung function decline.

Conclusions: Coexposure to DE and allergen impaired lung
function, which was worse after particle depletion (which increased
NO2). Thus, particulates are not necessarily the sole or main
culprit responsible for all harmful effects of DE. Policies and
technologies aimed at protecting public health should be scrutinized
in that regard.
Clinical trial registered with www.clinicaltrials.gov (NCT02017431).

Keywords: diesel exhaust; asthma; filter; genetic susceptibility


4140 Public Health, Young Seminar Room

Recent Events

EOH Dissertation Defense

Kristen Frawley - Methods for Assessing Cytochrome c Oxidase Inhibitors and Potential Antidotes

Tuesday 8/6 1:30PM - 2:30PM
1149 Public Health, Foster Conference Room

"Methods for Assessing Cytochrome c Oxidase Inhibitors and Potential Antidotes"

Date: Tuesday, August 6, 2019
Time: 1:30 pm
Location: Room 1149

Committee Members:
Jim Peterson, PhD 
Linda Pearce, PhD
Aaron Barchowsky, PhD
Joel Haight, PhD

 

ABSTRACT

Mitochondrial toxicants (sulfide, cyanide and/or azide) and their putative antidotes (NaNO2 and/or CoN4[11.3.1]) were examined in two models (BPAEC and Galleria mellonella) and compared to a mouse model. Bovine pulmonary artery endothelial cells (BPAEC) responded in a dose-dependent manner to millimolar (0-10) concentrations of sodium hydrosulfide (NaHS) and when treated five minutes before the NaHS with a sodium nitrite (NaNO2) solution there was a marked reversal in the mitochondrial-linked toxicity of sulfide. This was similar to the results observed in male Swiss-Webster mice administered NaNO2 prophylactically (24 mg/kg ip), five minutes before an LD40 dose of NaHS. In G. mellonella both nitrite and the Busch compound reduced the recovery time of cyanide, azide and sulfide poisoning, demonstrating the usefulness of this invertebrate organism for examining cytochrome c oxidase inhibitors and testing putative antidotes. Inoculation of the three toxicants by intra-haemocoel injection (ih) through the larval proleg, resulted in a dose-dependent unconscious or “knockdown” state and subsequent recovery, similar to the righting recovery observed in our animal studies. The time from knockdown until recovery was measurable in the larvae (<1 to ~40 min). Effectiveness of the antidotes was assessed by measuring the length of righting recovery in larvae treated with antidotes versus larvae receiving only the toxicant. These putative antidotes were shown to be helpful in ameliorating the toxicity of all three toxicants in cells, mice and G. mellonella larvae, especially in the case of sulfide and azide toxicity, since there are no effective antidotes available. Most importantly, NaNO2 ameliorated cyanide toxicity in the larvae. The larvae do not have hemoglobin, demonstrating that the antidotal action of nitrites does not require involvement of methemoglobin, verifying that NaNO2 acts as a NO donor and not a methemoglobin former.

Last Updated On Tuesday, July 23, 2019 by Snyder, Bryanna M
Created On Tuesday, July 23, 2019

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