Exposure to ambient ultrafine particles has been associated with cardiopulmonary toxicity and mortality. Adverse effects specifically linked include loss of sympathovagal balance altered hemostasis.To characterize the acute exposure in young healthy humans.Nineteen nonsmoking male female subjects between ages 18 35 were exposed filtered air or an atmosphere which captured (<0.16 microm) concentrated by a factor up 20-fold over levels use particle concentrators fitted size-selective outlets...

E-cigarettes containing 'nicotine salts' aim to increase smoker's satisfaction by improving blood nicotine delivery and other sensory properties. Here, we evaluated the pharmacokinetic profiles subjective effects of from two e-cigarette device platforms with varying concentrations lactate (nicotine salt) e-liquid relative conventional cigarettes. A randomised, open-label, cross-over clinical study was conducted in 15 healthy US adult smokers. Five different products were consecutively on...

Background: There is ample epidemiologic and toxicologic evidence that exposure to fine particulate matter (PM) air pollution [aerodynamic diameter ≤ 2.5 µm (PM )], which derives primarily from combustion processes, can result in increased mortality morbidity.There less certainty as the contribution of coarse PM 2.5-10 ), crustal materials mechanical morbidity.oBjective: To determine whether causes cardiopulmonary effects, we exposed 14 healthy young volunteers concentrated ambient particles...

Changes in fifteen urine, blood and exhaled breath BoEs of HPHCs representing classes compounds reported by FDA to be significant contributors smoking-associated disease risks were measured 105 clinical-confined subjects following randomization a five-day forced-switch from usual brand conventional combustible cigarettes to: (i) exclusive commercial e-cigarette use; (ii) dual-use e-cigarettes the subject's cigarette brand; or (iii) discontinued use all tobacco nicotine products. Levels...

Acute changes in select physiological parameters associated with cardiovascular physiology (systolic and diastolic blood pressure (BP) heart rate (HR)), pulmonary function (FVC, FEV1, exhaled CO NO) adverse events were measured 105 clinically confined subjects who randomized into groups that either completely or partially switched from conventional cigarettes to e-cigarettes discontinued using tobacco nicotine products altogether. Use of the for five days under various study conditions did...

Electronic cigarettes (e-cigarettes) are popular alternatives to conventional among adult smokers wishing reduce their exposure harmful smoke constituents. However, little information exists on the relative internal exposures resulting from exclusive or dual use of e-cigarettes. Measurements product use; adverse events; changes in smoking urge; and blood, urine exhaled breath biomarkers (BoE) representing toxicants believed contribute related diseases were made at baseline after five days...

This randomized, partially single-blinded, 6-period crossover clinical study of adult smokers compared the nicotine pharmacokinetics, impacts on smoking urge and tolerability various formulations one brand e-cigarettes with that a tobacco cigarette. Five different e-liquid containing 1.6 % 2.4 conventional cigarette were randomized among 24 subjects under two exposure sessions consisting 30-min controlled one-hour ad lib use period to assess plasma levels, adverse events. The session...

Electronic cigarettes (ECs) are becoming popular alternatives for smokers, but there has been limited study of their abuse liability. The objective this was to evaluate the liability three Vuse Solo ECs, ranging from 14 36 mg in nicotine content, relative high- and low-abuse comparator products (usual brand combustible gum, respectively) a group 45 EC-naïve smokers. Enrolled subjects' ratings subjective effects uptake over 6 h were used measure pharmacokinetics following in-clinic use each...

Particle size has been implicated by epidemiological and toxicological studies as an important determinant of the toxicity ambient particulate matter (PM). In effort to characterize cardiovascular, hematological pulmonary effects different PM fractions in humans, we have conducted controlled human exposures normal volunteers ultrafine-, fine- coarse- fraction concentrated from air Chapel Hill, North Carolina. Healthy non-smoking male female subjects between ages 18 35 participated these...

Coarse, fine, and ultrafine particulate matter (PM) fractions possess different physical properties chemical compositions may produce adverse health effects. Studies were undertaken to determine whether or not gene expression patterns be used discriminate among the three size fractions. Airway epithelial cells obtained from 6 normal individuals exposed Chapel Hill coarse, fine PM (250 μg/ml) for 24 h (n=3 each). RNA was isolated hybridized Affymetrix cDNA microarrays. Significant genes...

Context: Exposure to single pollutants e.g. particulate matter (PM) is associated with adverse health effects, but it does not represent a real world scenario that usually involves multiple pollutants.Objectives: Determine if simultaneous exposure PM and NO2 results in synergistic interactions.Materials methods: Healthy young volunteers were exposed clean air, nitrogen dioxide (NO2, 0.5 ppm), concentrated fine particles from Chapel Hill air (PM2.5CAPs, 89.5 ± 10.7 µg/m3), or NO2+PM2.5CAPs...

This study examined changes in biomarkers of exposure (BoE) after 5 days nicotine-salt pod system (NSPS) use, compared with continuation usual-cigarette smoking and cigarette abstinence, among adult combustible smokers.

We previously reported that following a short-term product use period, of non-menthol Vuse Solo electronic cigarettes (ECs) resulted in effect-related subjective responses and nicotine uptake between those combustible (high-abuse liability comparator) gum (low-abuse comparator); the results were generally closer to gum.

Gender‐based differences in cytochrome P450 (CYP) activity may occur due to endogenous hormonal fluctuations with the menstrual cycle, which are altered by oral contraceptives. This study assessed average and within‐subject variability CYP3A4 CYP2D6 men, women taking Triphasil®, regularly menstruating not receiving Thirty‐three healthy volunteers participated this 28‐day pilot (12 Triphasil®) (OCs), 11 on exogenous progesterone or estrogen (no OCs), 10 men. activities were phenotyped...

Haiyan Tong*a, Ana G. Rappolda, Melissa Caugheyb, Alan L. Hinderliterb, Donald W. Graffc, Jon H. Berntsend, Wayne E. Cascioa, Robert B. Devlina & James M. Sametaa Environmental Public Health Division, National and Effects Research Laboratory, US Protection Agency, Triangle Park NCUSAb Department of Medicine, University North Carolina at Chapel Hill School Medicine Hill, NCUSAc Celerion Lincoln, NEUSAd TRC Corporation Raleigh, NCUSA

Soluble particulate matter (PM) components (e.g., metals) have the potential to be absorbed into bloodstream and transported heart where they might induce expression of inflammatory cytokines remodel electrical properties. We exposed cultured rat ventricular myocytes similar concentrations two metals [zinc (Zn) vanadium (V)] found commonly in PM measured changes spontaneous beat rate. statistically significant reductions rate after both short-term (4-hr) long-term (24-hr) exposures, with a...

Background Phenytoin, a cytochrome P450 (CYP) 2C9 substrate, has narrow therapeutic index and nonlinear pharmacokinetics. Therefore there is the potential for significant concentration‐related adverse effects when phenytoin coadministered with other CYP2C9 substrates. Losartan, an antihypertensive agent, also substrate CYP2C9. Objective Our objective was to assess of losartan on pharmacokinetics in healthy population volunteers. Methods A prospective, randomized, 3‐period crossover study...

The objective of this study was to examine the pharmacokinetic and pharmacodynamic consequences concomitant administration fluoxetine carvedilol in heart failure patients. Fluoxetine (20 mg) or matching placebo administered a randomized, double‐blind, two‐period crossover 10 patients previously identified as extensive metabolizers CYP2D6 substrates. Patients were maintained on dose 25 50 mg bid given fluoxetine/placebo for minimum 28 days. Plasma collected over 12‐hour dosing interval,...

Identifying the mechanisms by which air pollution causes human health effects is a daunting task. Airsheds around world are composed of mixtures made up hundreds chemical and biological components with an extensive array physicochemical properties. Current in vivo approaches limited to identification associations between pollutants but do not allow for precise effect or component(s) responsible effect. High-throughput vitro methods using relevant cell culture systems microarray technology...

Novel noncombustible tobacco products offer adult smokers (ASs) alternatives to combustible cigarettes lower on the continuum of risk; however, abuse potential such has not been well studied. The objective this study was evaluate 2 chewable tobacco-derived nicotine containing products, VERVE Chews Blue Mint (test 1) and Green 2), in ASs compared with own-brand (CIGS) polacrilex gum (GUM) using subjective measures pharmacokinetics. used test during a 5-day at-home trial prior completing an...