Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-11 (of 11 Records) |
Query Trace: Hearn B[original query] |
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Pyrethroid resistance in the New World malaria vector Anopheles albimanus is mediated by cytochrome P450 CYP6P5
Kusimo MO , Mackenzie-Impoinvil L , Ibrahim SS , Muhammad A , Irving H , Hearn J , Lenhart AE , Wondji CS . Pestic Biochem Physiol 2022 183 105061 Pyrethroid resistance in the malaria vector Anopheles albimanus presents an obstacle to malaria elimination in the Americas. Here, An. albimanus CYP6P5 (the most overexpressed P450 in a Peruvian population) was functionally characterized. Recombinant CYP6P5 metabolized the type II pyrethroids, deltamethrin and α-cypermethrin with comparable affinities (K(M) of 3.3 μM ± 0.4 and 3.6 μM ± 0.5, respectively), but exhibited a 2.7-fold higher catalytic rate for α-cypermethrin (k(cat) of 6.02 min(-1) ± 0.2) versus deltamethrin (2.68 min(-1) ± 0.09). Time-course assays revealed progressive depletion of the above pyrethroids with production of four HPLC-detectable metabolites. Low depletion was obtained with type I pyrethroid, permethrin. Transgenic expression in Drosophila melanogaster demonstrated that overexpression of CYP6P5 alone conferred type II pyrethroid resistance, with only 16% and 55.3% mortalities in flies exposed to 0.25% α-cypermethrin and 0.15% deltamethrin, respectively. Synergist bioassays using P450 inhibitor piperonylbutoxide significantly recovered susceptibility (mortality = 73.6%, p < 0.001) in synergized flies exposed to 4% piperonylbutoxide, plus 0.25% α-cypermethrin, compared to non-synergized flies (mortality = 4.9%). Moderate resistance was also observed towards 4% DDT. These findings established the preeminent role of CYP6P5 in metabolic resistance in An. albimanus, highlighting challenges associated with deployment of insecticide-based control tools in the Americas. |
Hydrogen cyanide and aromatic amine yields in the mainstream smoke of 60 little cigars
Ai J , Hassink M , Taylor KM , Deycard VN , Hearn B , Williams K , McGuigan M , Valentin-Blasini L , Watson CH . Chem Res Toxicol 2022 35 (6) 940-953 Mainstream smoke yields of hydrogen cyanide (HCN) and three aromatic amines, 1-aminonaphthalene, 2-aminonaphthalene, and 4-aminobiphenyl, from 60 little cigar brands currently on the US market were measured for both International Organization for Standardization (ISO) and Canadian Intense (CI) smoking regimens. The smoke yields are compared with those from 50 cigarette products measured by Counts et al. of Philip Morris USA (PMUSA) in 2005 [Counts et al. Regul. Toxicol. Pharmacol. 2005 41, 185-227] and 50 cigarette products measured by the Centers for Disease Control and Prevention (CDC) in cooperation with the Food and Drug Administration (FDA) in 2012 [Tynan et al. Consumption of Cigarettes and Combustible Tobacco: United States, 2000-2011. In Morbidity and Mortality Weekly Report; Centers for Disease Control and Prevention, 2012; 565-580]. For the little cigars, the average HCN yield with the ISO smoking regimen is 335 μg/cigar (range: 77-809 μg/cigar), which is 332% higher than the average of 50 PMUSA 2005 cigarettes and 243% higher than the average of 50 CDC/FDA 2012 cigarettes. For the CI smoking regimen, the average HCN yield is 619 μg/cigar (range: 464-1045 μg/cigar), which is 70.5% higher than the average of 50 PMUSA 2005 cigarettes and 69% higher than the average of the 50 CDC/FDA 2012 cigarettes. For aromatic amines, the average ISO smoking regimen smoke yields are 36.6 ng/cigar (range: 15.9-70.6 ng/cigar) for 1-aminonaphthalene, 24.6 ng/cigar (range: 12.3-36.7 ng/cigar) for 2-aminonaphthalene, and 5.6 ng/cigar (range: 2.3-17.2 ng/cigar) for 4-aminobiphenyl. The average ISO yields of aromatic amines from little cigars are 141% to 210% higher compared to the average yields of 50 PMUSA cigarettes. The average CI smoke regimen yields are 73.0 ng/cigar (range: 32.1-112.2 ng/cigar) for 1-aminonaphthalene, 45.2 ng/cigar (range: 24.6-74.8 ng/cigar) for 2-aminonaphthalene, and 12.7 ng/cigar (range: 5.5-37.5 ng/cigar) for 4-aminobiphenyl. The average CI aromatic amine yields are 143% to 220% higher compared to the average yields of 50 PMUSA cigarettes, almost identical to the relative yields under the ISO smoking regimen. Both HCN and aromatic amine yields are 1.5× to 3× higher for the tested little cigars than for the conventional cigarettes; however, there are notable differences in the relationships of these yields to certain product characteristics, such as weight, ventilation, and tobacco type. The higher smoke yields of these compounds from little cigars indicates that cigar smokers may be at risk of a higher exposure to HCN and aromatic amines on a per stick basis and thus increased health concerns. |
Multi-year Study of PAHs in Mainstream Cigarette Smoke
Hearn BA , Ding YS , Watson CH , Johnson TL , Zewdie G , Jeong-Im JH , Walters MJ , Holman MR , Rochester CG . Tob Regul Sci 2018 4 (3) 96-106 OBJECTIVES: Correlations are made between mainstream cigarette smoke deliveries of individual PAHs over multiple years. Average overall PAH deliveries in mainstream cigarette smoke by study year, mentholation, ring size, and manufacturer are compared. METHODS: Mainstream smoke deliveries were determined by GC/MS for 14 polycyclic aromatic hydrocarbons (PAHs) from selected cigarettes on the US market in 2002, 2004, 2007, and 2011. The mainstream smoke PAH emissions were measured under international standardization organization (ISO) smoking conditions. Pearson product-moment correlation was used to examine the linear relationship among the PAHs over multiple years. RESULTS: A number of the PAH analytes were statistically highly correlated with each other. The overall average for mainstream smoke deliveries of PAHs did not change significantly between study years. Similar levels in average PAH deliveries were seen for mentholated and non-mentholated cigarettes. CONCLUSIONS: The strong correlations between PAH compounds over multiple years show that a limited set of PAHs can predict deliveries of others with confidence over multiple years. A more limited panel of analytes may be considered when designing studies involving PAH measurements in mainstream smoke. |
Chemical characterization of mainstream smoke from SPECTRUM VARIABLE NICOTINE RESEARCH CIGARETTES
Ding YS , Richter P , Hearn B , Zhang L , Bravo R , Yan X , Perez JJ , Chan M , Hughes J , Chen P , Chen W , Wong J , Holmberg S , Smith S , Larango M , Valentin-Blasini L , Watson CH . Tob Regul Sci 2017 3 (1) 81-94 OBJECTIVE: Our objective was to characterize mainstream smoke constituent deliveries from SPECTRUM variable nicotine research cigarettes under 2 machine smoking regimens. SPECTRUM cigarettes are manufactured by the 22nd Century company for the National Institute on Drug Abuse, National Institutes of Health to contain varying (including reduced) levels of nicotine. METHODS: Mainstream smoke constituent deliveries of "tar," nicotine, carbon monoxide, tobacco-specific nitrosamines (N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)), benzo[a]pyrene, aromatic amines, and carbonyls were analyzed in 23 varieties of SPECTRUM cigarettes using ISO 17025 accredited methods. RESULTS: Data are presented as means and standard deviations of 5 replicates for all analytes. CONCLUSIONS: Under the ISO smoking regimen, mean levels of many smoke emissions for SPECTRUM varieties were comparable to the 3R4F research cigarette. Calculated SPECTRUM elasticity ranged from 1.6 to 4.0. Accordingly, under intense machine smoking conditions differences in emissions of SPECTRUM cigarettes were apparent. In addition, NNN increased with smoke nicotine while the same rate of change was not seen for NNK. It is important to monitor levels of chemicals of public health concern and regulatory interest as technologies emerge to reduce levels of nicotine or other targeted chemicals in tobacco products. |
Polycyclic aromatic hydrocarbons in the mainstream smoke of popular U.S. cigarettes
Vu AT , Taylor KM , Holman MR , Ding YS , Hearn B , Watson CH . Chem Res Toxicol 2015 28 (8) 1616-26 The mainstream smoke yields of 14 polycyclic aromatic hydrocarbons (PAHs) were determined for 50 commercial U.S. cigarettes using a validated GC/MS method with the International Organization of Standardization (ISO) and Canadian Intense (CI) smoking machine regimens. PAH mainstream smoke deliveries vary widely among the commercial cigarettes with the ISO smoking regimen primarily because of differing filter ventilation. The more abundant, lower molecular weight PAHs such as naphthalene, fluorene, and phenanthrene predominantly comprise the total PAH yields. In contrast, delivery yields of high molecular weight PAHs such as benzo[b]fluoranthene, benzo[e]pyrene, benzo[k]fluoranthene, and benzo[a]pyrene (BaP) are much lower. Comparative analysis of PAHs deliveries shows brand specific differences. Correlation analysis shows strong positive associations between BaP and most of the other PAHs as well as total PAHs. The results suggest that BaP may be a representative marker for other PAH constituents in cigarette smoke generated from similarly blended tobacco, particularly those PAHs with similar molecular weights and chemical structures. |
A high throughput method for estimating mouth-level intake of mainstream cigarette smoke
Yan X , Zhang L , Hearn BA , Valentin-Blasini L , Polzin GM , Watson CH . Nicotine Tob Res 2015 17 (11) 1324-30 INTRODUCTION: We developed a high throughput method for estimating smoker's mainstream smoke intake on a per-cigarette basis by analyzing discarded cigarette butts. This new method utilizes ultraviolet/visible (UV-Vis) spectrophotometric analysis of isopropanol-soluble smoke particulate matter extracted from discarded cigarette filters. METHODS: When measured under a wide range of smoking conditions for a given brand variant, smoking machine delivery of nicotine, benzene, polycyclic aromatic hydrocarbons, and tobacco-specific nitrosamines can be related to the overall filter extract absorbance at 360nm. Once this relationship has been established, UV-Vis analysis of a discarded cigarette filter butt gives a quantitative measure of a smoker's exposure to these analytes. RESULTS: The measured mainstream smoke constituents correlated closely (correlation coefficients from 0.9303 to 0.9941) with the filter extract absorbance. These high correlations held over a wide range of smoking conditions for 2R4F research cigarettes as well as popular domestic cigarette brands sold in the United States. CONCLUSIONS: This low cost, high throughput method is suitable for high volume analyses (hundreds of samples per day) because UV-Vis spectrophotometry, rather than mass spectrometry, is used for the cigarette filter butt analysis. This method provides a stable and noninvasive means for estimating mouth-level delivery of many mainstream smoke constituents. The ability to gauge the mouth-level intake of harmful chemicals and total mainstream smoke for cigarette smokers in a natural setting on a cigarette-by-cigarette basis can provide insights on factors contributing to morbidity and mortality from cigarette smoking, as well as insights on strategies related to smoking cessation. |
An MHC class I immune evasion gene of Marek?s disease virus.
Hearn Cari, Preeyanon Likit, Hunt Henry D, York Ian A. Virology 2015 Jan 15. 47588-95 . Virology 2015 Jan 15. 47588-95 Hearn Cari, Preeyanon Likit, Hunt Henry D, York Ian A. Virology 2015 Jan 15. 47588-95 |
Chemical analysis of Alaskan iq'mik smokeless tobacco
Hearn BA , Renner CC , Ding YS , Vaughan-Watson C , Stanfill SB , Zhang L , Polzin GM , Ashley DL , Watson CH . Nicotine Tob Res 2013 15 (7) 1283-8 INTRODUCTION: Iq'mik, a form of smokeless tobacco (ST), is traditionally used by Cup'ik and Yup'ik Eskimo people of western Alaska. Iq'mik is sometimes incorrectly considered to be a healthier alternative to smoking because its ingredients are perceived as "natural." Our chemical characterization of iq'mik shows that iq'mik is not a safe alternative to smoking or other ST use. METHODS: We measured nicotine and pH levels of tobacco and ash used to prepare iq'mik. We also characterized levels of toxins which are known to be present in ST including tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) using chromatographic separations coupled with isotope dilution mass spectrometry. RESULTS: Nicotine content in the iq'mik tobacco was very high, ranging from 35 to 43mg/g, with a mean of 39mg/g. The pH of the iq'mik tobacco-ash mixture was 11, an extremely high level compared with most ST products. High levels of PAHs were seen in the fire-cured tobacco samples with a benzo[a]pyrene level of 87ng/g. Average TSNA levels in the tobacco were 34, 2,700, and 340ng/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N'-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. CONCLUSIONS: Iq'mik contains high levels of the more easily absorbed unionized nicotine as well as known carcinogenic TSNAs and PAHs. The perception that iq'mik is less hazardous than other tobacco products due to the use of "natural" ingredients is not warranted. This chemical characterization of iq'mik gives a better understanding of the risk of possible adverse health effects of its use. |
Development of a method to estimate mouth-level benzo[a]pyrene intake by filter analysis
Ding Y , Chou T , Abdul-Salaam S , Hearn B , Watson CH . Cancer Epidemiol Biomarkers Prev 2011 21 (1) 39-44 BACKGROUND: Benzo[a]pyrene is one of the most potent carcinogens generated in cigarette smoke. During smoking, cigarette filters trap a significant portion of mainstream smoke benzo[a]pyrene. This trapped portion is proportional to what exits the end of the filter and is drawn into the smoker's mouth. METHODS: We developed a new method to estimate mouth-level benzo[a]pyrene intake using filter analysis. In this analysis, cigarettes are smoked by a smoking machine using a variety of conditions to yield a range of mainstream smoke deliveries, which approximate a range of human puffing characteristics. Mainstream smoke benzo[a]pyrene collected on Cambridge filter pads and the corresponding 1-cm mouth-end cigarette filter butts is extracted, purified by solid phase extraction, and quantified by high performance liquid chromatography coupled with a fluorescence detector. Based on the amount of benzo[a]pyrene retained in cigarette butts and the amount collected on pads, we can relate them using a linear regression model. RESULTS: Using this model and subsequently analyzing cigarette filters collected from smokers, we are able to estimate their mouth-level intakes, which smokers received when they consumed cigarettes. We made a series of measurements using research cigarettes and select commercial cigarettes having a wide range of machine smoke "tar" and nicotine deliveries. CONCLUSIONS: In all cases, results indicate a linear relation of benzo[a]pyrene between cigarette filter butts and Cambridge filter pads, with R2 ranging from 0.93 to 0.98. IMPACT: This technique provides a non-invasive means to examine intake on a per cigarette basis to examine both exposure and behavioral aspects of smoking. |
Semi-volatiles in mainstream smoke delivery from select charcoal-filtered cigarette brand variants
Hearn BA , Ding YS , Vaughan C , Zhang L , Polzin G , Caudill SP , Watson CH , Ashley DL . Tob Control 2010 19 (3) 223-30 BACKGROUND: It has been reported that charcoal added to cigarette filters selectively removes many of the more volatile chemicals, but it is not clear to what extent charcoal may reduce the delivery of important less volatile chemical constituents in mainstream cigarette smoke. METHODS: We analysed machine-derived mainstream smoke deliveries (under three smoking regimens) for variants of a charcoal-filtered cigarette commercially test-marketed in the USA, focusing on selected polycyclic aromatic hydrocarbons (PAHs), phenols and tobacco-specific nitrosamines (TSNAs). Results While charcoal-containing filters selectively removed lower molecular weight PAHs from mainstream smoke, they did not significantly remove the heavier and more toxic PAHs studied, such as benzo[a]pyrene, a known carcinogen. Likewise, charcoal-containing filters removed phenols and TSNAs from mainstream smoke to differing amounts depending on the compound, filter design and the smoking regimen. CONCLUSIONS: The addition of sufficient charcoal to cigarette filters is known to remove many volatile compounds and can potentially reduce deliveries of certain semi-volatile compounds under some machine smoking regimens. Less volatile compounds, with a significant portion in the particulate phase, are less available for selective filtration by charcoal-containing filters than the more volatile compounds that reside predominantly in the gas phase. |
Implementing packaged HIV-prevention interventions for HIV-positive individuals: considerations for clinic-based and community-based interventions
Collins CB Jr , Hearn KD , Whittier DN , Freeman A , Stallworth JD , Phields M . Public Health Rep 2010 125 55-63 Providing efficacious human immunodeficiency virus (HIV) prevention services to HIV-positive individuals is an appropriate strategy to reduce new infections. The Centers for Disease Control and Prevention (CDC) has identified interventions with evidence of efficacy for prevention with positives (PwP). Through its process of disseminating evidence-based interventions (EBIs), CDC has attempted to diffuse four of these interventions into practice. One of these interventions has been diffused to community-based organizations, whereas another has been diffused to medical clinics serving HIV-positive people. A third intervention was originally developed with HIV-positive individuals using methadone, but uptake by methadone clinics has not occurred. A fourth intervention for HIV-positive adolescents and young adults has had disappointing adoption levels. Unique implementation challenges have been encountered in various intervention settings. Lessons learned in the dissemination of the first four PwP interventions will facilitate implementation of three new PwP EBIs currently being packaged for dissemination. |
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