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1.
Sci Total Environ ; 861: 160609, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36470384

RESUMO

While mounting evidence suggests that wildland fire smoke (WFS) inhalation may increase the burden of cardiopulmonary disease, the occupational risk of repeated exposure during wildland firefighting remains unknown. To address this concern, we evaluated the cardiopulmonary function in mice following a cumulative exposure to lab-scale WFS equivalent to a mid-length wildland firefighter (WLFF) career. Dosimetry analysis indicated that 80 exposure hours at a particulate concentration of 22 mg/m3 yield in mice the same cumulative deposited mass per unit of lung surface area as 3600 h of wildland firefighting. To satisfy this condition, male Apoe-/- mice were whole-body exposed to either air or smoldering Douglas fir smoke (DFS) for 2 h/day, 5 days/week, over 8 consecutive weeks. Particulate size in DFS fell within the respirable range for both mice and humans, with a count median diameter of 110 ± 20 nm. Expiratory breath hold in mice exposed to DFS significantly reduced their minute volume (DFS: 27 ± 4; Air: 122 ± 8 mL/min). By the end of the exposure time frame, mice in the DFS group exhibited a thicker (DFS: 109 ± 3; Air: 98 ± 3 µm) and less distensible (DFS: 23 ± 1; Air: 28 ± 1 MPa-1) aorta with reduced diastolic blood augmentation capacity (DFS: 53 ± 2; Air: 63 ± 2 kPa). Cardiac magnetic resonance imaging further revealed larger end-systolic volume (DFS: 14.6 ± 1.1; Air: 9.9 ± 0.9 µL) and reduced ejection-fraction (DFS: 64.7 ± 1.0; Air: 75.3 ± 0.9 %) in mice exposed to DFS. Consistent with increased airway epithelium thickness (DFS: 10.4 ± 0.8; Air: 7.6 ± 0.3 µm), airway Newtonian resistance was larger following DFS exposure (DFS: 0.23 ± 0.03; Air: 0.20 ± 0.03 cmH2O-s/mL). Furthermore, parenchyma mean linear intercept (DFS: 36.3 ± 0.8; Air: 33.3 ± 0.8 µm) and tissue thickness (DFS: 10.1 ± 0.5; Air: 7.4 ± 0.7 µm) were larger in DFS mice. Collectively, mice exposed to DFS manifested early signs of cardiopulmonary dysfunction aligned with self-reported events in mid-career WLFFs.


Assuntos
Pseudotsuga , Animais , Masculino , Camundongos , Aorta , Poeira , Exposição por Inalação/análise , Pulmão , Fumaça/efeitos adversos , Volume Sistólico
2.
Inhal Toxicol ; 34(9-10): 260-274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35793285

RESUMO

OBJECTIVE: Electronic cigarettes (e-cigs) are popular nicotine delivery devices, yet the health effects remain unclear. To determine equivalent biomarkers, we characterized the immediate response in Apoe-/- mice exposed to tank/box-mod e-cig (e-cigtank), pod e-cig (e-cigpod), or cig smoke. MATERIALS AND METHODS: Reproducible puff profiles were generated for each aerosol and delivered to Apoe-/- mice via a nose-only exposure system. Serum cotinine levels were quantified at various time points through ELISA and utilized to model cotinine pharmacokinetics. In addition, particle size measurements and mouse respiratory function were characterized to calculate particle dosimetry. RESULTS AND DISCUSSION: Cig and e-cigtank particles were lognormally distributed with similar count median diameters (cig: 178 ± 2, e-cigtank: 200 ± 34nm), while e-cigpod particles were bimodally distributed and smaller (116 ± 13 and 13.3 ± 0.4 nm). Minute volumes decreased with cig exposure (5.4 ± 2.7 mL/min) compared to baseline (90.8 ± 11.6 mL/min), and less so with e-cigtank (45.2 ± 9.2 mL/min) and e-cigpod exposures (58.6 ± 6.8 mL/min), due to periods of apnea in the cig exposed groups. Cotinine was absorbed and eliminated most rapidly in the e-cigpod group (tmax = 14.5; t1/2' = 51.9 min), whereas cotinine was absorbed (cig: 50.4, e-cigtank: 40.1 min) and eliminated (cig: 104.6, e-cigtank: 94.1 min) similarly in the cig and e-cigtank groups. For exposure times which equate the area under the cotinine-concentration curve, ∼6.4× (e-cigtank) and 4.6× (e-cigpod) more nicotine deposited in e-cig compared to cig exposed mice. CONCLUSIONS: This study provides a basis for incorporating cotinine pharmacokinetics into preclinical exposure studies, allowing for longitudinal studies of structural and functional changes due to exposure.


This study highlights that pod e-cigs deliver smaller particles than tank/box-mode e-cigs and cig smoke. Minute volumes were substantially reduced in cig smoke-exposed mice, due to periods of apnea, whereas only expiration times increased in the e-cig-exposed groups. More particles deposit in e-cig exposed mice, compared to the cig group, for equivalent daily area under the cotinine concentration curve.


Assuntos
Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Aerossóis , Animais , Apolipoproteínas E/genética , Cotinina , Camundongos
3.
Matter ; 3(3): 950-962, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32838296

RESUMO

In response to the COVID-19 pandemic, cloth masks are being used to control the spread of virus, but the efficacy of these loose-fitting masks is not well known. Here, tools and methods typically used to assess tight-fitting respirators were modified to quantify the efficacy of community-produced and commercially produced fabric masks as personal protective equipment. Two particle counters concurrently sample ambient air and air inside the masks; mask performance is evaluated by mean particle removal efficiency and statistical variability when worn as designed and with a nylon overlayer, to independently assess fit and material. Worn as designed, both commercial surgical masks and cloth masks had widely varying effectiveness (53%-75% and 28%-91% particle removal efficiency, respectively). Most surgical-style masks improved with the nylon overlayer, indicating poor fit. This rapid testing method uses widely available hardware, requires only a few calculations from collected data, and provides both a holistic and aspect-wise evaluation of mask performance.

4.
Inhal Toxicol ; 32(5): 200-217, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32475185

RESUMO

Objective: The rapid increase of cannabis consumption reinforces the need to elucidate the health hazards of this practice. The presence of fine particulate matter in cannabis smoke and vapor poses a major concern, as it may contribute to cardiopulmonary disease. To facilitate the assessment of risks associated with cannabis inhalation, we developed and characterized a method for exposing mice to cannabis in a way that mimics the delivery of the drug to the airways of smokers. Materials and Methods: Cannabis (10.3% THC, 0.05% CBD) was vaporized to generate aerosols with a reproducible particle profile. Aerosols were acutely delivered to male, adult C57BL/6 mice via a nose-only exposure system. Serum THC levels were measured for increasing cannabis doses. Blood pressure and heart rate were recorded at baseline and following exposure. Behavioral response to cannabis inhalation in the open field was documented. Awake neurological activity upon cannabis exposure was monitored using BOLD fMRI.Results and Discussion: Cannabis aerosols contained particles with count median diameter of 243 ± 39 nm and geometric standard deviation of 1.56 ± 0.06. Blood serum THC levels increased linearly with aerosolized mass and peaked at 136 ± 5 ng/mL. Cannabis inhalation decreased heart rate and blood pressure but promoted anxiety-like behavior. Observed differences in BOLD activation volumes linked cannabis to increased awareness to sensory stimuli and reduced behavioral arousal.Conclusions: Quantified physiological, behavioral, and neurological responses served as validation for our mouse model of cannabis inhalation. Animal models of aerosol exposure will be instrumental for uncovering the health outcomes of chronic cannabis use.


Assuntos
Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cannabis , Dronabinol/sangue , Fumar Maconha , Modelos Animais , Administração por Inalação , Administração Intranasal , Aerossóis , Animais , Encéfalo/diagnóstico por imagem , Humanos , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Tamanho da Partícula , Sistema Respiratório/metabolismo , Volatilização
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