Assessment of nicotine concentration in electronic nicotine delivery system (ENDS) liquids and precision of dosing to aerosol.

PubMed

Kosmider, Leon; Sobczak, Andrzej; Szołtysek-Bołdys, Izabela; Prokopowicz, Adam; Skórka, Agnieszka; Abdulafeez, Oluyadi; Koszowski, Bartosz

2015-01-01

Global use of electronic nicotine delivery systems (ENDS; also called electronic cigarettes, e-cigarettes) has increased dramatically in recent years. However, due to the limited safety studies and growing concerns on the potential toxicity from long term use of ENDS, many national and international governments have employed regulatory measures to curtail its use. One of the most significant challenges regulators of ENDS encounter is the lack of quality standards to assess ENDS, e-liquid (solution used with ENDS which contain nicotine--a highly toxic and addictive substance), and amount of nicotine delivery to aerosol during ENDS use. Aims of the study were to (1) measure and compare nicotine concentration in e-liquids to values reported by manufacturers on packaging labels; (2) assess the precision of nicotine delivery from tank during aerosol formation. Methods: Nine popular Polish e-liquids (based on the market share data from October 2014) were purchased for the study. The labelled nicotine concentration for the selected e-liquids ranged between 11-25 mg/mL. All e-liquids were aerosolized in the laboratory using a smoking simulation machine (Palaczbot). Each e-liquid was aerosolized in a series of 6 consecutive bouts. A single bout consisted of 15 puffs with the following puff topography: 65 mL puff volume, 2.8 sec. puff duration, and 19 sec. interpuff interval. A total of 90 puffs were generated from each e-liquid. Nicotine content in the e-liquids and the aerosol generated were determined by gas chromatography with thermionic sensitive detection (GC-TSD). For seven of nine analyzed e-liquids, the difference between measured and manufacturer labeled nicotine concentration was less than 10%. Nicotine dose in aerosol per bout ranged between 0.77-1.49 mg (equivalent to one-half the nicotine a smoker inhales from a single combustible cigarette). Our analysis showed the high consistency between the labeled and measured nicotine concentration for popular on the

Indoor concentrations of nicotine in low-income, multi-unit housing: associations with smoking behaviours and housing characteristics

PubMed Central

Kraev, TA; Adamkiewicz, G; Hammond, SK; Spengler, JD

2017-01-01

Objective An analysis of airborne nicotine measurements collected in 49 low-income, multi-unit residences across the Greater Boston Area. Methods Nicotine concentrations were determined using passive monitors placed in homes over a one-week sampling period and air exchange rates (AER) were sampled using the perfluorocarbon tracer technique. Residents were surveyed through a questionnaire about smoking behaviour and a visual inspection was conducted to collect information on housing characteristics contributing to secondhand smoke (SHS) exposure. Using a mass balance model to account for the air exchange rate, volume of the home and sorption and re-emission of nicotine on indoor surfaces, the effective smoking rate (SReff) was determined for each residence. Results Nicotine levels ranged from the limit of detection to 26.92 µg/m3, with a mean of 2.20 µg/m3 and median of 0.13 µg/m3. Nicotine measurements were significantly associated with the number of smokers in the household and the number of cigarettes smoked in the home. The results of this study suggest that questionnaire reports can provide a valid estimate of residential exposure to tobacco smoke. In addition, this study found evidence that tobacco smoke contamination in low-income housing developments is not limited to homes with smokers (either residing in the home or visiting). The frequent report of tobacco smoke odour coming from other apartments or hallways resulted in increased levels of nicotine concentrations and SReff in non-smoking homes, suggestive of SHS infiltration from neighbouring units. Conclusion These findings have important implications for smoking regulations in multi-unit homes and highlight the need to reduce involuntary exposure to tobacco smoke among low-income housing residents. PMID:19679890

Indoor concentrations of nicotine in low-income, multi-unit housing: associations with smoking behaviours and housing characteristics.

PubMed

Kraev, T A; Adamkiewicz, G; Hammond, S K; Spengler, J D

2009-12-01

An analysis of airborne nicotine measurements collected in 49 low-income, multi-unit residences across the Greater Boston Area. Nicotine concentrations were determined using passive monitors placed in homes over a one-week sampling period and air exchange rates (AER) were sampled using the perfluorocarbon tracer technique. Residents were surveyed through a questionnaire about smoking behaviour and a visual inspection was conducted to collect information on housing characteristics contributing to secondhand smoke (SHS) exposure. Using a mass balance model to account for the air exchange rate, volume of the home and sorption and re-emission of nicotine on indoor surfaces, the effective smoking rate (SR(eff)) was determined for each residence. Nicotine levels ranged from the limit of detection to 26.92 microg/m(3), with a mean of 2.20 microg/m(3) and median of 0.13 microg/m(3). Nicotine measurements were significantly associated with the number of smokers in the household and the number of cigarettes smoked in the home. The results of this study suggest that questionnaire reports can provide a valid estimate of residential exposure to tobacco smoke. In addition, this study found evidence that tobacco smoke contamination in low-income housing developments is not limited to homes with smokers (either residing in the home or visiting). The frequent report of tobacco smoke odour coming from other apartments or hallways resulted in increased levels of nicotine concentrations and SR(eff) in non-smoking homes, suggestive of SHS infiltration from neighbouring units. These findings have important implications for smoking regulations in multi-unit homes and highlight the need to reduce involuntary exposure to tobacco smoke among low-income housing residents.

Dermal uptake of nicotine from air and clothing: Experimental verification.

PubMed

Bekö, G; Morrison, G; Weschler, C J; Koch, H M; Pälmke, C; Salthammer, T; Schripp, T; Eftekhari, A; Toftum, J; Clausen, G

2018-03-01

This study aims to elucidate in greater detail the dermal uptake of nicotine from air or from nicotine-exposed clothes, which was demonstrated recently in a preliminary study. Six non-smoking participants were exposed to gaseous nicotine (between 236 and 304 μg/m 3 ) over 5 hours while breathing clean air through a hood. Four of the participants wore only shorts and 2 wore a set of clean clothes. One week later, 2 of the bare-skinned participants were again exposed in the chamber, but they showered immediately after exposure instead of the following morning. The 2 participants who wore clean clothes on week 1 were now exposed wearing a set of clothes that had been exposed to nicotine. All urine was collected for 84 hours after exposure and analyzed for nicotine and its metabolites, cotinine and 3OH-cotinine. All participants except those wearing fresh clothes excreted substantial amounts of biomarkers, comparable to levels expected from inhalation intake. Uptake for 1 participant wearing exposed clothes exceeded estimated intake via inhalation by >50%. Biomarker excretion continued during the entire urine collection period, indicating that nicotine accumulates in the skin and is released over several days. Absorbed nicotine was significantly lower after showering in 1 subject but not the other. Differences in the normalized uptakes and in the excretion patterns were observed among the participants. The observed cotinine half-lives suggest that non-smokers exposed to airborne nicotine may receive a substantial fraction through the dermal pathway. Washing skin and clothes exposed to nicotine may meaningfully decrease exposure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Measuring PM2.5, Ultrafine Particles, Nicotine Air and Wipe Samples Following the Use of Electronic Cigarettes.

PubMed

Melstrom, Paul; Koszowski, Bartosz; Thanner, Meridith Hill; Hoh, Eunha; King, Brian; Bunnell, Rebecca; McAfee, Tim

2017-09-01

Few studies have examined the extent of inhalation or dermal contact among bystanders following short-term, secondhand e-cigarette exposure. Measure PM2.5 (particles < 2.5 microns), UF (ultrafine particles < 100 nm), and nicotine in air and deposited on surfaces and clothing pre-/during/post- a short-term (2-hour) e-cigarette exposure. E-cigarettes were used ad libitum by three experienced users for 2 hours during two separate sessions (disposable e-cigarettes, then tank-style e-cigarettes, or "tanks") in a 1858 ft3 room. We recorded: uncorrected PM2.5 (using SidePak); UF (using P-Trak); air nicotine concentrations (using air samplers; SKC XAD-4 canisters); ambient air exchange rate (using an air capture hood). Wipe samples were taken by wiping 100 cm2 room surfaces pre- and post- both sessions, and clean cloth wipes were worn during the exposure and collected at the end. Uncorrected PM2.5 and UF were higher (p < .0001) during sessions than before or after. Median PM2.5 during exposure was higher using tanks (0.515 mg/m3) than disposables (0.035 mg/m3) (p < .0001). Median UF during exposure was higher using disposables (31 200 particles/cm3) than tanks (25 200 particles/cm3)(p < .0001). Median air nicotine levels were higher (p < .05) during both sessions (disposables = 0.697 ng/L, tanks = 1.833 ng/L) than before (disposables = 0.004 ng/L, tanks = 0.010 ng/L) or after (disposables = 0.115 ng/L, tanks = 0.147 ng/L). Median accumulation rates of nicotine on surface samples were 2.1 ng/100 cm2/h using disposables and 4.0 ng/100 cm2/h using tanks; for cloth samples, it was 44.4 ng/100 cm2/h using disposables and 69.6 ng/100 cm2/h using tanks (p < .01). Mean room ventilation rate was ~5 air changes per hour during both sessions. Short-term e-cigarette use can produce: elevated PM2.5; elevated UF; nicotine in the air; and accumulation of nicotine on surfaces and clothing. Short-term indoor e-cigarette use produced accumulation of nicotine on surfaces and clothing, which

Effects of User Puff Topography, Device Voltage, and Liquid Nicotine Concentration on Electronic Cigarette Nicotine Yield: Measurements and Model Predictions

PubMed Central

Talih, Soha; Balhas, Zainab; Eissenberg, Thomas; Salman, Rola; Karaoghlanian, Nareg; El Hellani, Ahmad; Baalbaki, Rima; Saliba, Najat

2015-01-01

Introduction: Some electronic cigarette (ECIG) users attain tobacco cigarette–like plasma nicotine concentrations while others do not. Understanding the factors that influence ECIG aerosol nicotine delivery is relevant to regulation, including product labeling and abuse liability. These factors may include user puff topography, ECIG liquid composition, and ECIG design features. This study addresses how these factors can influence ECIG nicotine yield. Methods: Aerosols were machine generated with 1 type of ECIG cartridge (V4L CoolCart) using 5 distinct puff profiles representing a tobacco cigarette smoker (2-s puff duration, 33-ml/s puff velocity), a slow average ECIG user (4 s, 17 ml/s), a fast average user (4 s, 33 ml/s), a slow extreme user (8 s, 17 ml/s), and a fast extreme user (8 s, 33 ml/s). Output voltage (3.3–5.2 V or 3.0–7.5 W) and e-liquid nicotine concentration (18–36 mg/ml labeled concentration) were varied. A theoretical model was also developed to simulate the ECIG aerosol production process and to provide insight into the empirical observations. Results: Nicotine yields from 15 puffs varied by more than 50-fold across conditions. Experienced ECIG user profiles (longer puffs) resulted in higher nicotine yields relative to the tobacco smoker (shorter puffs). Puff velocity had no effect on nicotine yield. Higher nicotine concentration and higher voltages resulted in higher nicotine yields. These results were predicted well by the theoretical model (R 2 = 0.99). Conclusions: Depending on puff conditions and product features, 15 puffs from an ECIG can provide far less or far more nicotine than a single tobacco cigarette. ECIG emissions can be predicted using physical principles, with knowledge of puff topography and a few ECIG device design parameters. PMID:25187061

Effects of user puff topography, device voltage, and liquid nicotine concentration on electronic cigarette nicotine yield: measurements and model predictions.

PubMed

Talih, Soha; Balhas, Zainab; Eissenberg, Thomas; Salman, Rola; Karaoghlanian, Nareg; El Hellani, Ahmad; Baalbaki, Rima; Saliba, Najat; Shihadeh, Alan

2015-02-01

Some electronic cigarette (ECIG) users attain tobacco cigarette-like plasma nicotine concentrations while others do not. Understanding the factors that influence ECIG aerosol nicotine delivery is relevant to regulation, including product labeling and abuse liability. These factors may include user puff topography, ECIG liquid composition, and ECIG design features. This study addresses how these factors can influence ECIG nicotine yield. Aerosols were machine generated with 1 type of ECIG cartridge (V4L CoolCart) using 5 distinct puff profiles representing a tobacco cigarette smoker (2-s puff duration, 33-ml/s puff velocity), a slow average ECIG user (4 s, 17 ml/s), a fast average user (4 s, 33 ml/s), a slow extreme user (8 s, 17 ml/s), and a fast extreme user (8 s, 33 ml/s). Output voltage (3.3-5.2 V or 3.0-7.5 W) and e-liquid nicotine concentration (18-36 mg/ml labeled concentration) were varied. A theoretical model was also developed to simulate the ECIG aerosol production process and to provide insight into the empirical observations. Nicotine yields from 15 puffs varied by more than 50-fold across conditions. Experienced ECIG user profiles (longer puffs) resulted in higher nicotine yields relative to the tobacco smoker (shorter puffs). Puff velocity had no effect on nicotine yield. Higher nicotine concentration and higher voltages resulted in higher nicotine yields. These results were predicted well by the theoretical model (R (2) = 0.99). Depending on puff conditions and product features, 15 puffs from an ECIG can provide far less or far more nicotine than a single tobacco cigarette. ECIG emissions can be predicted using physical principles, with knowledge of puff topography and a few ECIG device design parameters. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Concentration of Nicotine and Glycols in 27 Electronic Cigarette Formulations

PubMed Central

Peace, Michelle R.; Baird, Tyson R.; Smith, Nathaniel; Wolf, Carl E.; Poklis, Justin L.; Poklis, Alphonse

2016-01-01

Personal battery-powered vaporizers or electronic cigarettes were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. Electronic cigarettes and their e-cigarette liquid formulations are virtually unregulated. These formulations are typically composed of propylene glycol and/or glycerin, flavoring components and an active drug, such as nicotine. Twenty-seven e-cigarette liquid formulations that contain nicotine between 6 and 22 mg/L were acquired within the USA and analyzed by various methods to determine their contents. They were screened by Direct Analysis in Real Time™ Mass Spectrometry (DART-MS). Nicotine was confirmed and quantitated by high-performance liquid chromatography–tandem mass spectrometry, and the glycol composition was confirmed and quantitated by gas chromatography–mass spectrometry. The DART-MS screening method was able to consistently identify the exact mass peaks resulting from the protonated molecular ion of nicotine, glycol and a number of flavor additives within 5 mmu. Nicotine concentrations were determined to range from 45 to 131% of the stated label concentration, with 18 of the 27 have >10% variance. Glycol composition was generally accurate to the product description, with only one exception where the propylene glycol to glycerin percentage ratio was stated as 50:50 and the determined concentration of propylene glycol to glycerin was 81:19 (% v/v). No unlabeled glycols were detected in these formulations. PMID:27165804

Concentration of Nicotine and Glycols in 27 Electronic Cigarette Formulations.

PubMed

Peace, Michelle R; Baird, Tyson R; Smith, Nathaniel; Wolf, Carl E; Poklis, Justin L; Poklis, Alphonse

2016-07-01

Personal battery-powered vaporizers or electronic cigarettes were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. Electronic cigarettes and their e-cigarette liquid formulations are virtually unregulated. These formulations are typically composed of propylene glycol and/or glycerin, flavoring components and an active drug, such as nicotine. Twenty-seven e-cigarette liquid formulations that contain nicotine between 6 and 22 mg/L were acquired within the USA and analyzed by various methods to determine their contents. They were screened by Direct Analysis in Real Time™ Mass Spectrometry (DART-MS). Nicotine was confirmed and quantitated by high-performance liquid chromatography-tandem mass spectrometry, and the glycol composition was confirmed and quantitated by gas chromatography-mass spectrometry. The DART-MS screening method was able to consistently identify the exact mass peaks resulting from the protonated molecular ion of nicotine, glycol and a number of flavor additives within 5 mmu. Nicotine concentrations were determined to range from 45 to 131% of the stated label concentration, with 18 of the 27 have >10% variance. Glycol composition was generally accurate to the product description, with only one exception where the propylene glycol to glycerin percentage ratio was stated as 50:50 and the determined concentration of propylene glycol to glycerin was 81:19 (% v/v). No unlabeled glycols were detected in these formulations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Intravenous and oral suicidal e-liquid poisonings with confirmed nicotine and cotinine concentrations.

PubMed

Sommerfeld, Karina; Łukasik-Głębocka, Magdalena; Kulza, Maksymilian; Drużdż, Artur; Panieński, Paweł; Florek, Ewa; Zielińska-Psuja, Barbara

2016-05-01

The increasing availability of e-cigarettes is a potential toxicological concern. E-cigarettes appeared on the Polish market in 2006, and since 2009 they have been widely available with a new source of nicotine, the so-called e-liquid. In this paper two cases of suicidal oral and intravenous poisonings with the e-liquid are described. The clinical courses of these poisonings are presented. Nicotine and cotinine concentrations in the patient's blood were determined using high performance liquid chromatography with diode array detection. In the course of intoxication patient No. 1, classic symptoms of acute nicotine poisoning without convulsions were observed. Nicotine and cotinine concentrations measured in serum were 0.096 and 4.4mg/L, respectively. The case of patient No. 2, admission with no typical symptoms of nicotine poisoning was identified, except unconsciousness and slow respiration. Nicotine and cotinine concentrations in the serum at the time of No. 2 admissions were determined to be 0.8 and 1.3mg/L, respectively. With the increasing number of e-liquid poisonings cases, it should be aware that these products can be a readily available source of poison. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nicotine Vapor Method to Induce Nicotine Dependence in Rodents.

PubMed

Kallupi, Marsida; George, Olivier

2017-07-05

Nicotine, the main addictive component of tobacco, induces potentiation of brain stimulation reward, increases locomotor activity, and induces conditioned place preference. Nicotine cessation produces a withdrawal syndrome that can be relieved by nicotine replacement therapy. In the last decade, the market for electronic cigarettes has flourished, especially among adolescents. The nicotine vaporizer or electronic nicotine delivery system is a battery-operated device that allows the user to simulate the experience of tobacco smoking without inhaling smoke. The device is designed to be an alternative to conventional cigarettes that emits vaporized nicotine inhaled by the user. This report describes a procedure to vaporize nicotine in the air to produce blood nicotine levels in rodents that are clinically relevant to those that are observed in humans and produce dependence. We also describe how to construct the apparatus to deliver nicotine vapor in a stable, reliable, and consistent manner, as well as how to analyze air for nicotine content. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

PubMed Central

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

2015-01-01

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMN). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30µM). Previous work showed that the paralytic mutant zebrafish known as sofa potato, exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. PMID:25668718

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at differentmore » developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose

Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

PubMed

Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří

2017-05-01

Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach) , a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

[Nicotine and benz(alpha)piren concentration in saliva of inveterate tobacco-smokers].

PubMed

Zurabashvili, Z A; Chanturiaia, I L; Kapanadze, L R

2009-11-01

The aim of the work is study in saliva the nicotine and benz(alphapiren concentration dynamic in morning without cigarette, after light first cigarette and after one hour after lighting. All biochemical substances is analyzed and identified chromatographically on Bondo-Pac C(18) column (Liquid Chromatography Millipor-Waters, USA). The conducted quantitative and qualitative analyzes show that at all examinations benz(alpha)piren concentration dynamic in saliva is very differently in compare of nicotine concentration dynamic. The content of benz(alpha)piren in saliva at all analyzes transfer very slowly. Our data show that with the increase of the time the concentration of nicotine in saliva in beginning increase, add then diminish. The studies are necessary to be held in different directions. First, the medical consequences of using the tobacco and the ways of their curing should be identified. The second direction should mean elaboration of preventive measures and programs, or measures of intervention.

Distribution analysis of airborne nicotine concentrations in hospitality facilities.

PubMed

Schorp, Matthias K; Leyden, Donald E

2002-02-01

A number of publications report statistical summaries for environmental tobacco smoke (ETS) concentrations. Despite compelling evidence for the data not being normally distributed, these publications typically report the arithmetic mean and standard deviation of the data, thereby losing important information related to the distribution of values contained in the original data. We were interested in the frequency distributions of reported nicotine concentrations in hospitality environments and subjected available data to distribution analyses. The distribution of experimental indoor airborne nicotine concentration data taken from hospitality facilities worldwide was fit to lognormal, Weibull, exponential, Pearson (Type V), logistic, and loglogistic distribution models. Comparison of goodness of fit (GOF) parameters and indications from the literature verified the selection of a lognormal distribution as the overall best model. When individual data were not reported in the literature, statistical summaries of results were used to model sets of lognormally distributed data that are intended to mimic the original data distribution. Grouping the data into various categories led to 31 frequency distributions that were further interpreted. The median values in nonsmoking environments are about half of the median values in smoking sections. When different continents are compared, Asian, European, and North American median values in restaurants are about a factor of three below levels encountered in other hospitality facilities. On a comparison of nicotine concentrations in North American smoking sections and nonsmoking sections, median values are about one-third of the European levels. The results obtained may be used to address issues related to exposure to ETS in the hospitality sector.

Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

PubMed

Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

2017-01-01

Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

Associations between self-reported in-home smoking behaviours and surface nicotine concentrations in multiunit subsidised housing.

PubMed

Hood, Nancy E; Ferketich, Amy K; Klein, Elizabeth G; Pirie, Phyllis; Wewers, Mary Ellen

2014-01-01

Smoke-free policies are being increasingly promoted and adopted in subsidised multiunit housing to address disparities in residential secondhand smoke exposure. In order to inform the planning and evaluation of these policies, this study examined associations between self-reported in-home smoking and surface nicotine concentrations. A face-to-face, cross-sectional survey was conducted from August to October 2011 with leaseholders in a probability sample of private subsidised housing units in Columbus, Ohio, without an existing smoke-free housing policy (n=301, 64% response rate). After the survey, a wipe sample was collected from a wood surface in the living room to measure surface nicotine concentrations (n=279). In-home smoking was reported by 56.6% of respondents. Geometric mean surface nicotine concentrations differed between non-smoking and smoking homes (11.4 vs 90.9 μg/m(2); p<0.001), and between homes with complete, partial and no voluntary home smoking restrictions (8.9 vs 56.3 vs 145.6 μg/m(2); p<0.001). Surface nicotine concentrations were moderately correlated (r=.52) with the total number of cigarettes smoked indoors per week. Smoking behaviours of respondents, other household members and visitors, and length of stay were independently associated with surface nicotine concentrations in a multivariable model, explaining 52% of the variance. Surface nicotine concentrations were significantly associated with a range of self-reported in-home smoking behaviours. This measure should be considered for evaluating changes in in-home smoking behaviours after implementation of smoke-free policies by subsidised housing providers. More research is needed about how surface nicotine concentrations differ over space, time and various indoor surfaces.

Evaluation of methods for simultaneous collection and determination of nicotine and polynuclear aromatic hydrocarbons in indoor air

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuang, J.C.; Kuhlman, M.R.; Wilson, N.K.

1990-01-01

A study was performed to determine whether one sampling system and one analytical method can be used to measure both polynuclear aromatic hydrocarbons (PAH) and nicotine. The PAH collection efficiencies for both XAD-2 and XAD-4 adsorbents are very similar, but the nicotine collection efficiency was greater for XAD-4. The spiked perdeuterated PAH were retained well in both adsorbents after exposure to more than 300 cu m of air. A two-step Soxhlet extraction, dichloromethane followed by ethylacetate, was used to remove nicotine and PAH from XAD-4. The extract was analyzed by positive chemical ionization or electron impact gas chromatography/mass spectrometry (GC/MS)more » to determine nicotine and PAH. It is shown that one sampling system (quartz fiber filter and XAD-4 in series) and one analytical method (Soxhlet extraction and GC/MS) can be used to measure both nicotine and PAH in indoor air.« less

Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hussein, Jabeen; Farkas, Svetlana; MacKinnon, Yolanda

Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderatemore » to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers.« less

REINFORCING EFFECTS OF NICOTINE AND NON-NICOTINE COMPONENTS OF CIGARETTE SMOKE

PubMed Central

Rose, Jed E.; Salley, Al; Behm, Frederique M.; Bates, James E.; Westman, Eric C.

2014-01-01

We assessed the reinforcing effects of nicotine and non-nicotine components of cigarette smoke, by presenting a concurrent choice paradigm in which participants had access to intravenous (IV) nicotine infusions vs. saline (placebo) infusions and puffs from denicotinized (“denic”) cigarettes vs. air (sham puffs). We also measured the effects on self-administration of prior satiation with each component. Sixteen smokers participated in 7 sessions, consisting of: 1) a baseline smoking assessment, which was used to tailor the nicotine dose per infusion to that of puffs from subjects’ preferred brands of cigarettes; 2) two sessions in which participants were trained to discriminate IV nicotine vs. saline infusions and denic smoke vs. sham (air) puffs; and 3) four sessions assessing choice behavior after different satiation conditions. Results showed that subjects self-administered more puffs of denic smoke than any other alternative, including IV nicotine. IV nicotine, however, was preferred over IV saline and sham puffs. Preference for denic smoke vs. IV nicotine was highly correlated with subjective ratings of “comfort” associated with the two alternatives. Satiation with smoke diminished the number of denic puffs taken during choice periods, while prior administration of nicotine did not affect the number of puffs taken. Smoking withdrawal symptoms were alleviated both by nicotine administration and by denic smoke. These results show that in established smokers, non-nicotine aspects of cigarette smoking have potent reinforcing effects. While current smoking cessation pharmacotherapies primarily address the nicotine component of cigarette addiction, future cessation strategies should also be designed to target non-nicotine factors. PMID:20358364

Associations of Electronic Cigarette Nicotine Concentration With Subsequent Cigarette Smoking and Vaping Levels in Adolescents.

PubMed

Goldenson, Nicholas I; Leventhal, Adam M; Stone, Matthew D; McConnell, Rob S; Barrington-Trimis, Jessica L

2017-12-01

Research indicates that electronic cigarette (e-cigarette) use (vaping) among adolescents is associated with the initiation and progression of combustible cigarette smoking. The reasons for this association are unknown. To evaluate whether use of e-cigarettes with higher nicotine concentrations is associated with subsequent increases in the frequency and intensity of combustible cigarette smoking and vaping. In this prospective cohort study involving students from 10 high schools in the Los Angeles, California, metropolitan area, surveys were administered during 10th grade in the spring (baseline) and 11th grade in the fall (6-month follow-up) of 2015 to students who reported using e-cigarettes within the past 30 days and the nicotine concentration level they used at baseline. Self-report of baseline e-cigarette nicotine concentration of none (0 mg/mL), low (1-5 mg/mL), medium (6-17 mg/mL), or high (≥18 mg/mL) typically used during the past 30 days. Frequency of combustible cigarette smoking and e-cigarette use within the past 30 days (0 days [none], 1-2 days [infrequent], or ≥3 days [frequent]) and daily intensity of smoking and vaping (number of cigarettes smoked per day, number of vaping episodes per day, and number of puffs per vaping episode) at the 6-month follow-up. The analytic sample included 181 students (96 boys [53.0%] and 85 girls [47.0%]; mean [SD] age, 16.1 [0.4] years). Each successive increase in nicotine concentration (none to low, low to medium, and medium to high) vaped was associated with a 2.26 (95% CI, 1.28-3.98) increase in the odds of frequent (vs no) smoking and a 1.65 (95% CI, 1.09-2.51) increase in the odds of frequent (vs no) vaping at follow-up after adjustment for baseline frequency of smoking and vaping and other relevant covariates. Use of e-cigarettes with high (vs no) nicotine concentration was associated with a greater number of cigarettes smoked per day at follow-up (adjusted rate ratio [RR], 7.03; 95% CI, 6.11-7.95). An

Therapeutic concentrations of varenicline in the presence of nicotine increase action potential firing in human adrenal chromaffin cells.

PubMed

Hone, Arik J; Michael McIntosh, J; Rueda-Ruzafa, Lola; Passas, Juan; de Castro-Guerín, Cristina; Blázquez, Jesús; González-Enguita, Carmen; Albillos, Almudena

2017-01-01

Varenicline is a nicotinic acetylcholine receptor (nAChR) agonist used to treat nicotine addiction, but a live debate persists concerning its mechanism of action in reducing nicotine consumption. Although initially reported as α4β2 selective, varenicline was subsequently shown to activate other nAChR subtypes implicated in nicotine addiction including α3β4. However, it remains unclear whether activation of α3β4 nAChRs by therapeutically relevant concentrations of varenicline is sufficient to affect the behavior of cells that express this subtype. We used patch-clamp electrophysiology to assess the effects of varenicline on native α3β4* nAChRs (asterisk denotes the possible presence of other subunits) expressed in human adrenal chromaffin cells and compared its effects to those of nicotine. Varenicline and nicotine activated α3β4* nAChRs with EC 50 values of 1.8 (1.2-2.7) μM and 19.4 (11.1-33.9) μM, respectively. Stimulation of adrenal chromaffin cells with 10 ms pulses of 300 μM acetylcholine (ACh) in current-clamp mode evoked sodium channel-dependent action potentials (APs). Under these conditions, perfusion of 50 or 100 nM varenicline showed very little effect on AP firing compared to control conditions (ACh stimulation alone), but at higher concentrations (250 nM) varenicline increased the number of APs fired up to 436 ± 150%. These results demonstrate that therapeutic concentrations of varenicline are unlikely to alter AP firing in chromaffin cells. In contrast, nicotine showed no effect on AP firing at any of the concentrations tested (50, 100, 250, and 500 nM). However, perfusion of 50 nM nicotine simultaneously with 100 nM varenicline increased AP firing by 290 ± 104% indicating that exposure to varenicline and nicotine concurrently may alter cellular behavior such as excitability and neurotransmitter release. © 2016 International Society for Neurochemistry.

Indoor air-assessment: Indoor concentrations of environmental carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gold, K.W.; Naugle, D.F.; Berry, M.A.

1991-01-01

In the report, indoor concentration data are presented for the following general categories of air pollutants: radon-222, environmental tobacco smoke (ETS), asbestos, gas phase organic compounds, formaldehyde, polycyclic aromatic hydrocarbons (PAH), pesticides, and inorganic compounds. These pollutants are either known or suspect carcinogens (i.e., radon-222, asbestos) or more complex mixtures or classes of compounds which contain known or suspect carcinogens. Concentration data for individual carcinogenic compounds in complex mixtures are usually far from complete. The data presented for complex mixtures often include compounds which are not carcinogenic or for which data are insufficient to evaluate carcinogenicity. Their inclusion is justified,more » however, by the possibility that further work may show them to be carcinogens, cocarcinogens, initiators or promotors, or that they may be employed as markers (e.g., nicotine, acrolein) for the estimation of exposure to complex mixtures.« less

Environmental fate and effects of nicotine released during cigarette production.

PubMed

Seckar, Joel A; Stavanja, Mari S; Harp, Paul R; Yi, Yongsheng; Garner, Charles D; Doi, Jon

2008-07-01

A variety of test methods were used to study the gradation, bioaccumulation, and toxicity of nicotine. Studies included determination of the octanol-water partition coefficient, conversion to CO2 in soil and activated sludge, and evaluation of the effects on microbiological and algal inhibition as well as plant germination and root elongation. The partitioning of nicotine between octanol and water indicated that nicotine will not bioaccumulate regardless of the pH of the medium. The aqueous and soil-based biodegradation studies indicated that nicotine is readily biodegradable in both types of media. The microbiological inhibition and aquatic and terrestrial toxicity tests indicated that nicotine has low toxicity. The U.S. Environmental Protection Agency Persistence, Bioaccumulation, and Toxicity Profiler model, based on the structure of nicotine and the predictive rates of hydroxyl radical and ozone reactions, estimated an atmospheric half-life of less than 5.0 h. Using this value in the Canadian Environmental Modeling Center level III model, the half-life of nicotine was estimated as 3.0 d in water and 0.5 d in soil. This model also estimated nicotine discharge into the environment; nicotine would be expected to be found predominantly in water (93%), followed by soil (4%), air (3%), and sediment (0.4%). Using the estimated nicotine concentrations in water, soil, and sediment and the proper median effective concentrations derived from the algal growth, biomass inhibition, and buttercrunch lettuce (Lactuca sativa) seed germination and root elongation studies, hazard quotients of between 10(-7) and 10(-8) were calculated, providing further support for the conclusion that the potential for nicotine toxicity to aquatic and terrestrial species in the environment is extremely low.

Nicotine Dependence and Urinary Nicotine, Cotinine and Hydroxycotinine Levels in Daily Smokers.

PubMed

Van Overmeire, Ilse P I; De Smedt, Tom; Dendale, Paul; Nackaerts, Kristiaan; Vanacker, Hilde; Vanoeteren, Jan F A; Van Laethem, Danny M G; Van Loco, Joris; De Cremer, Koen A J

2016-09-01

Nicotine dependence and smoking frequency are critical factors for smoking cessation. The aims of this study are (1) to determine if nicotine dependence Fagerström Test for Nicotine Dependence (FTND) scores are associated with urinary levels of nicotine metabolites, (2) to assess the relationship of hydroxycotinine/cotinine ratio with FTND score and cigarettes smoked per day (CPD), and (3) to identify significant predictors of cigarettes per day among biomarker concentrations and individual FTND items. Urine samples and questionnaire data of 239 daily smokers were obtained. Nicotine, cotinine and hydroxycotinine urinary levels were determined by UPLC MS/MS.Multiple linear regression models were developed to explore the relationship between nicotine, cotinine, hydroxycotinine levels and separate FTND scores (for all six items). We found significant correlations between the different urinary biomarker concentrations, and the FTND score. The time before the first cigarette after waking (TTFC) was significantly associated with the nicotine, cotinine and hydroxycotinine concentrations. No association was found between the ratio of hydroxycotinine to cotinine and either the FTND or the CPD. A model including four FTND questions, sex, age, and the cotinine concentration, accounted for 45% of the variance of CPD. There are significant relationships between urinary levels of nicotine, cotinine, and hydroxycotinine and the FTND score. Especially the FTND question about TTFC is relevant for explaining the biomarker concentrations. CPD (below 15) was significantly explained by four FTND dependence items and urinary cotinine levels in a regression model. We investigated associations between urinary levels of nicotine, cotinine, and hydroxycotinine in daily smokers and the FTND scores for nicotine dependence. We did not find association between the hydroxycotinine/cotinine ratio and CPD. We developed a model that explains the cigarettes smoked daily (CPD) in a group of light

Evaluation of methods for simultaneous collection and determination of nicotine and polynuclear aromatic hydrocarbons in indoor air

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuang, J.C.; Kuhlman, M.R.; Wilson, N.K.

1990-05-01

A study was performed to determine whether one sampling system and one analytical method can be used to collect and measure both polynuclear aromatic hydrocarbons (PAHs) and nicotine. PAH collection efficiencies for both XAD-2 and XAD-4 adsorbents were very similar, but nicotine collection efficiency was greater for XAD-4. Spiked perdeuterated PAHs were retained well in both adsorbents after exposure to more than 300 m{sup 3} of air. A two-step Soxhlet extraction, dichloromethane followed by ethyl acetate, was used to remove nicotine and PAHs from XAD-4. The extract was analyzed by positive chemical ionization or electron impact gas chromatography/mass spectrometry (GC/MS)more » to determine nicotine and PAHs. It is shown that one sampling system (quartz fiber filter and XAD-4 in series) and one analytical method (Soxhlet extraction and GC/MS) can be used for both nicotine and PAHs in indoor.« less

Nicotine behavioral pharmacology: clues from planarians

PubMed Central

Rawls, Scott M.; Patil, Tanvi; Tallarida, Christopher S.; Baron, Steven; Kim, Myongji; Song, Kevin; Ward, Sara; Raffa, Robert B.

2011-01-01

Background Nicotine is one of the world’s most addictive substances and the primary reason that humans inhale tobacco smoke. The pharmacological effects of nicotine can be investigated in planarians, aquatic flatworms that possess an integrated neural network including cephalic ganglia that some consider the earliest “brain” and spinal cord. Here, we tested the hypothesis that nicotine exposure elicits mammalian-like behaviors in planarians. Methods Planarian motility and stereotypy (C-shape hyperkinesias) were quantified following acute nicotine exposure. During repeated nicotine exposure, we investigated the presence of withdrawal, tolerance, behavioral sensitization, and environmental place conditioning. Results Acute nicotine exposure increased stereotypical activity and elicited biphasic effects on motility. A low concentration (0.01 mM) increased motility whereas higher concentrations (0.3 – 10 mM) elicited the opposite effect. Planarians exposed to nicotine (0.03 mM) for 60 min and then tested in water displayed reduced motility that was not observed during exposure to water, acute nicotine, or continuous nicotine. Nicotine-treated planarians withdrawn from the drug for 3 days before being challenged with nicotine displayed behavioral sensitization at low concentrations (0.1, 0.3 mM) but tolerance at higher concentrations (1, 3 mM). Planarians conditioned with nicotine in the ambient light (non-preferred environment) displayed a reduction in their natural preference for a dark environment. Conclusions The present results suggest nicotine elicits mammalian-like effects in planarians, including decreased motility and increased stereotypy following acute administration and abstinence-induced withdrawal, behavioral sensitization, tolerance, and place conditioning during repeated exposure. PMID:21530106

Assessment of indoor air quality at an electronic cigarette (Vaping) convention.

PubMed

Chen, Rui; Aherrera, Angela; Isichei, Chineye; Olmedo, Pablo; Jarmul, Stephanie; Cohen, Joanna E; Navas-Acien, Ana; Rule, Ana M

2017-12-29

E-cigarette (vaping) conventions are public events promoting electronic cigarettes, in which indoor use of e-cigarettes is allowed. The large concentration of people using e-cigarettes and poor air ventilation can result in indoor air pollution. In order to estimate this worst-case exposure to e-cigarettes, we evaluated indoor air quality in a vaping convention in Maryland (MD), USA. Real-time concentrations of particulate matter (PM 10 ) and real-time total volatile organic compounds (TVOCs), CO 2 and NO 2 concentrations were measured. Integrated samples of air nicotine and PM 10 concentrations were also collected. The number of attendees was estimated to range from 75 to 600 at any single observation time. The estimated 24-h time-weighted average (TWA) PM 10 was 1800 μg/m 3 , 12-fold higher than the EPA 24-h regulation (150 μg/m 3 ). Median (range) indoor TVOCs concentration was 0.13 (0.04-0.3) ppm. PM 10 and TVOC concentrations were highly correlated with CO 2 concentrations, indicating the high number of people using e-cigarettes and poor indoor air quality. Air nicotine concentration was 125 μg/m 3 , equivalent to concentrations measured in bars and nightclubs. E-cigarette aerosol in a vaping convention that congregates many e-cigarette users is a major source of PM 10 , air nicotine and VOCs, impairing indoor air quality. These findings also raise occupational concerns for e-cigarette vendors and other venue staff workers.

Absorption of nicotine and carbon monoxide from passive smoking under natural conditions of exposure.

PubMed Central

Jarvis, M J; Russell, M A; Feyerabend, C

1983-01-01

Seven non-smokers were exposed to tobacco smoke under natural conditions for two hours in a public house. Measures of nicotine and cotinine in plasma, saliva, and urine and expired air carbon monoxide all showed reliable increases. The concentrations of carbon monoxide and nicotine after exposure averaged 15.7% and 7.5% respectively of the values found in heavy smokers. Although the increase in expired air carbon monoxide of 5.9 ppm was similar to increases in smokers after a single cigarette, the amount of nicotine absorbed was between a tenth and a third of the amount taken in from one cigarette. Since this represented a relatively extreme acute natural exposure, any health risks of passive smoking probably depend less on quantitative factors than on qualitative differences between sidestream and mainstream smoke. PMID:6648864

A randomized trial of air cleaners and a health coach to improve indoor air quality for inner-city children with asthma and secondhand smoke exposure.

PubMed

Butz, Arlene M; Matsui, Elizabeth C; Breysse, Patrick; Curtin-Brosnan, Jean; Eggleston, Peyton; Diette, Gregory; Williams, D'Ann; Yuan, Jie; Bernert, John T; Rand, Cynthia

2011-08-01

To test an air cleaner and health coach intervention to reduce secondhand smoke exposure compared with air cleaners alone or no air cleaners in reducing particulate matter (PM), air nicotine, and urine cotinine concentrations and increasing symptom-free days in children with asthma residing with a smoker. Randomized controlled trial, with randomization embedded in study database. The Johns Hopkins Hospital Children's Center and homes of children. Children with asthma, residing with a smoker, randomly assigned to interventions consisting of air cleaners only (n = 41), air cleaners plus a health coach (n = 41), or delayed air cleaner (control) (n = 44). Changes in PM, air nicotine, and urine cotinine concentrations and symptom-free days during the 6-month study. The overall follow-up rate was high (91.3%). Changes in mean fine and coarse PM (PM(2.5) and PM(2.5-10)) concentrations (baseline to 6 months) were significantly lower in both air cleaner groups compared with the control group (mean differences for PM(2.5) concentrations: control, 3.5 μg/m(3); air cleaner only, -19.9 μg/m(3); and air cleaner plus health coach, -16.1 μg/m(3); P = .003; and PM(2.5-10) concentrations: control, 2.4 μg/m(3); air cleaner only, -8.7 μg/m(3); and air cleaner plus health coach, -10.6 μg/m(3); P = .02). No differences were noted in air nicotine or urine cotinine concentrations. The health coach provided no additional reduction in PM concentrations. Symptom-free days were significantly increased [corrected] in both air cleaner groups compared with the control group (P = .03). Although the use of air cleaners can result in a significant reduction in indoor PM concentrations and a significant increase in symptom-free days, it is not enough to prevent exposure to secondhand smoke.

Rats quit nicotine for a sweet reward following an extensive history of nicotine use.

PubMed

Huynh, Carmen; Fam, Justine; Ahmed, Serge H; Clemens, Kelly J

2017-01-01

Drug use may be exacerbated in environments which lack alternative means of engaging in rewarding behaviour. When alternative rewards are available, drug use may decrease-an effect that can be harnessed for therapeutic benefit. This idea is particularly well-supported by recent preclinical evidence demonstrating that a majority of rats will readily choose a potent non-drug reward over cocaine or heroin. Here we examine whether the same holds true for nicotine, a drug considered to have one of the highest addiction liabilities amongst drugs of abuse. Rats were trained to nose-poke separately for saccharin or nicotine on alternate days. Using a discrete-trial, forced-choice procedure, rats were then allowed to choose between nicotine and saccharin. This was followed by choice testing after a decrease in saccharin concentration (0.2-0%), omission of the fluid reward, an increase in nicotine concentration and following an extended nicotine self-administration history. All rats demonstrated a clear and immediate preference for saccharin at all times. This was despite variations in reward concentrations, or after an extensive nicotine history. Notably, rats preferred to nose-poke for water over nicotine and would omit responses when no fluid was delivered, rather than resume responding for nicotine. Overall, this study confirms and extends to nicotine previous research on other drugs of abuse, including cocaine and heroin. The ease with which rats quit nicotine in the present study contrasts with the well-known difficulty of humans to quit tobacco smoking. Possible factors that could explain this apparent discrepancy are discussed. © 2015 Society for the Study of Addiction.

Evaluation of sampling and analytical methods for nicotine and polynuclear aromatic hydrocarbon in indoor air. Final report, 1 February 1987-30 March 1987

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuang, J.C.; Kuhlman, M.R.; Hannan, S.W.

1987-11-01

The objective of this project was to evaluate a potential collection medium, XAD-4 resin, for collecting nicotine and polynuclear aromatic hydrocarbon (PAH) and to determine whether one collection system and one analytical method will allow quantification of both compound classes in air. The extraction efficiency study was to determine the extraction method to quantitatively remove nicotine and PAH from XAD-4 resin. The results showed that a two-step Soxhlet extraction consisting of dichloromethane followed by ethyl acetate resulted in the best recoveries for both nicotine and PAH. In the sampling efficiency study, XAD-2 and XAD-4 resin were compared, in parallel, formore » collection of PAH and nicotine. Quartz fiber filters were placed upstream of both adsorbents to collect particles. Prior to sampling, both XAD-2 and XAD-4 traps were spiked with known amounts (2 microgram) of perdeuterated PAH and D3-nicotine. The experiments were performed with cigarette smoking and nonsmoking conditions. The spiked PAH were retained well in both adsorbents after exposure to more than 300 cu. m. of indoor air. The spiked XAD-4 resin gave higher recoveries for D3-nicotine than did the spiked XAD-2 resin. The collection efficiency for PAH for both adsorbents is very similar but higher levels of nicotine were collected on XAD-4 resin.« less

Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.

PubMed

Teichert, Axel; Brossard, Patrick; Felber Medlin, Loyse; Sandalic, Larissa; Franzon, Mikael; Wynne, Chris; Laugesen, Murray; Lüdicke, Frank

2018-03-06

Novel nicotine delivery systems represent an evolving part of the tobacco harm reduction strategy. The pharmacokinetic (PK) profile of nicotine delivered by P3L, a pulmonary nicotine delivery system, and its effects on smoking urges and craving relief in relation to Nicorette inhalator were evaluated. This open-label, ascending nicotine levels study was conducted in 16 healthy smokers. Three different nicotine delivery levels, 50, 80, and 150 µg/puff, delivered by the P3L system were evaluated consecutively on different days after the use of the Nicorette inhalator. Venous nicotine PK, subjective effects, and tolerability were assessed. Geometric least-squares means for maximum plasma nicotine concentration (Cmax), generated by the mixed-effect model for exposure comparison, were 9.7, 11.2, and 9.8 ng/mL for the 50, 80, and 150 µg/puff P3L variants, respectively, compared to 6.1 ng/mL after Nicorette inhalator use. Median time from product use start to Cmax was 7.0 minutes for all P3L, compared to 30.0 minutes for the Nicorette inhalator. Craving reduction was slightly faster than with the Nicorette inhalator as assessed with the visual analog scale craving score. The mean Questionnaire of Smoking Urges -brief total scores did not differ for both products. P3L was well tolerated. At all three nicotine levels tested, the inhalation of the nicotine lactate aerosol delivered with the P3L provided plasma nicotine concentrations higher and faster compared to the Nicorette inhalator. The plasma nicotine concentration-time profile supports a pulmonary route of absorption for P3L compared to the oromucosal absorption of the Nicorette inhalator. The combination of nicotine and lactic acid with the P3L device shows potential over existing nicotine delivery systems by delivering nicotine with kinetics close to published data on conventional cigarettes and without exogenous carrier substances as used in current electronic nicotine delivery systems. Altogether, the PK profile

Electronic Nicotine Delivery Systems.

PubMed

Walley, Susan C; Jenssen, Brian P

2015-11-01

Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control. Copyright © 2015 by the American Academy of Pediatrics.

Electronic cigarettes and nicotine clinical pharmacology.

PubMed

Schroeder, Megan J; Hoffman, Allison C

2014-05-01

To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products' ability to support and maintain nicotine dependence. Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products' impact on public health.

Electronic cigarettes and nicotine clinical pharmacology

PubMed Central

Schroeder, Megan J; Hoffman, Allison C

2014-01-01

Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

Determination of Nicotine Absorption from Multiple Tobacco Products and Nicotine Gum

PubMed Central

Digard, Helena; Proctor, Christopher; Kulasekaran, Anuradha; Malmqvist, Ulf

2013-01-01

Introduction: Snus is a smokeless tobacco product traditionally used in Scandinavia and available in pouched or loose forms. The objective of this study was to determine nicotine absorption for current pouched and loose snus products in comparison with a cigarette and an over-the-counter nicotine gum. Methods: We conducted an open-label, randomized, 6-way, crossover study involving 20 healthy snus and cigarette users. One of 6 products (2 pouched snus, 2 weights of loose snus, a cigarette, and a nicotine gum) was administered at each of 6 visits. Blood samples were taken at intervals over 120 min and sensory perception assessed by questionnaire. Results: For the 4 smokeless tobacco products and the nicotine gum, blood plasma levels of nicotine were ranked according to total nicotine content as follows: loose snus (27.1 mg nicotine) > pouched snus (14.7 mg nicotine) > loose snus (10.8 mg nicotine) = pouched snus (10.7 mg nicotine) > nicotine gum (4.2 mg nicotine). The area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax) of nicotine ranged from 26.9 to 13.1 ng.h/ml and 17.9 to 9.1 ng.h/ml, respectively across all the products. Nicotine was absorbed more rapidly from the cigarette but systemic exposure was within the range of the smokeless tobacco products (AUC = 14.8 ng.h/ml; Cmax = 12.8 ng.h/ml). Conclusions: This study has generated new information on comparative nicotine absorption from a cigarette, loose snus, and pouched snus typical of products sold in Scandinavia. The similar nicotine absorption for 1 g portions of loose and pouched snus with approximately 11 mg of nicotine indicate that absorption kinetics were dependent on quantity of tobacco by weight and total nicotine content rather than product form. PMID:22585541

The effect of ozone on nicotine desorption from model surfaces:evidence for heterogeneous chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Destaillats, Hugo; Singer, Brett C.; Lee, Sharon K.

Assessment of secondhand tobacco smoke exposure using nicotine as a tracer or biomarker is affected by sorption of the alkaloid to indoor surfaces and by its long-term re-emission into the gas phase. However, surface chemical interactions of nicotine have not been sufficiently characterized. Here, the reaction of ozone with nicotine sorbed to Teflon and cotton surfaces was investigated in an environmental chamber by monitoring nicotine desorption over a week following equilibration in dry or humid air (65-70 % RH). The Teflon and cotton surfaces had N{sub 2}-BET surface areas of 0.19 and 1.17 m{sup 2} g{sup -1}, and water massmore » uptakes (at 70 % RH) of 0 and 7.1 % respectively. Compared with dry air baseline levels in the absence of O{sub 3}, gas phase nicotine concentrations decrease, by 2 orders of magnitude for Teflon after 50 h at 20-45 ppb O{sub 3}, and by a factor of 10 for cotton after 100 h with 13-15 ppb O{sub 3}. The ratios of pseudo first-order rate constants for surface reaction (r) to long-term desorption (k) were r/k = 3.5 and 2.0 for Teflon and cotton surfaces, respectively. These results show that surface oxidation was competitive with desorption. Hence, oxidative losses could significantly reduce long-term re-emissions of nicotine from indoor surfaces. Formaldehyde, N-methylformamide, nicotinaldehyde and cotinine were identified as oxidation products, indicating that the pyrrolidinic N was the site of electrophilic attack by O{sub 3}. The presence of water vapor had no effect on the nicotine-O{sub 3} reaction on Teflon surfaces. By contrast, nicotine desorption from cotton in humid air was unaffected by the presence of ozone. These observations are consistent with complete inhibition of ozone-nicotine surface reactions in an aqueous surface film present in cotton but not in Teflon surfaces.« less

Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors

PubMed Central

Moaddel, Ruin; Abdrakhmanova, Galia; Kozak, Joanna; Jozwiak, Krzysztof; Toll, Lawrence; Jimenez, Lucita; Rosenberg, Avraham; Tran, Thao; Xiao, Yingxian; Zarate, Carlos A.; Wainer, Irving W.

2012-01-01

The effect of the (R,S)-ketamine metabolites (R,S)-norketamine, (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)- hydroxynorketamine on the activity of α7 and α3β4 neuronal nicotinic acetylcholine receptors was investigated using patch-clamp techniques. The data indicated that (R,S)-dehydronorketamine inhibited acetylcholine-evoked currents in α7-nicotinic acetylcholine receptor, IC50 = 55 ± 6 nM, and that (2S,6S)-hydroxynorketamine, (2R,6R)-hydroxynorketamine and (R,S)-norketamine also inhibited α7-nicotinic acetylcholine receptor function at concentrations ≤1μM, while (R,S)-ketamine was inactive at these concentrations. The inhibitory effect of (R,S)-dehydronorketamine was voltage-independent and the compound did not competitively displace selective α7-nicotinic acetylcholine receptor ligands [125I]-α-bungarotoxin and [3H]-epibatidine indicating that (R,S)-dehydronorketamine is a negative allosteric modulator of the α7-nicotinic acetylcholine receptor. (R,S)-Ketamine and (R,S)-norketamine inhibited (S)-nicotine-induced whole-cell currents in cells expressing α3β4-nicotinic acetylcholine receptor, IC50 3.1 and 9.1μM, respectively, while (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine were weak inhibitors, IC50 >100μM. The binding affinities of (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine at the NMDA receptor were also determined using rat brain membranes and the selective NMDA receptor antagonist [3H]-MK-801. The calculated Ki values were 38.95 μM for (S)-dehydronorketamine, 21.19 μM for (2S,6S)-hydroxynorketamine and > 100 μM for (2R,6R)-hydroxynorketamine. The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug. PMID:23183107

Electronic cigarettes are a source of thirdhand exposure to nicotine.

PubMed

Goniewicz, Maciej L; Lee, Lily

2015-02-01

Substances remaining on the surfaces in areas where people have smoked contribute to thirdhand exposure. Nicotine from tobacco smoke has been shown to react with oxidizing chemicals in the air to form secondary pollutants, such as carcinogenic nitrosamines. While previous studies have demonstrated thirdhand exposure to nicotine from tobacco smoke, none have investigated whether nicotine from electronic cigarettes (e-cigarettes) can also be deposited on various surfaces. Three brands of e-cigarettes were refilled with varying nicotine concentrations. We released 100 puffs from each product directly into an exposure chamber. Surface wipe samples were taken from 5 indoor 100 cm(2) surfaces (window, walls, floor, wood, and metal) pre- and post-release of vapors. Nicotine was extracted from the wipes and was analyzed using gas chromatography. Three of the 4 experiments showed significant increases in the amount of nicotine on all five surfaces. The floor and glass windows had the greatest increases in nicotine, on average by a factor of 47 and 6, respectively (p < .05). The average amount of nicotine deposited on a floor during each experiment was 205 μg/m(2) and varied from limit of quantitation to 550 μg/m(2). This study indicates that there is a risk for thirdhand exposure to nicotine from e-cigarettes. Thirdhand exposure levels differ depending on the surface and the e-cigarette brand. Future research should explore the potential risks of thirdhand exposure to carcinogens formed from the nicotine that is released from e-cigarettes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analysis of nicotine-induced DNA damage in cells of the human respiratory tract.

PubMed

Ginzkey, Christian; Stueber, Thomas; Friehs, Gudrun; Koehler, Christian; Hackenberg, Stephan; Richter, Elmar; Hagen, Rudolf; Kleinsasser, Norbert H

2012-01-05

Epithelium of the upper and lower airways is a common origin of tobacco-related cancer. The main tobacco alkaloid nicotine may be associated with tumor progression. The potential of nicotine in inducing DNA mutations as a step towards cancer initiation is still controversially discussed. Different subtypes of nicotinic acetylcholine receptors (nAChR) are expressed in human nasal mucosa and a human bronchial cell line representing respiratory mucosa as a possible target for receptor-mediated pathways. In the present study, both cell systems were investigated with respect to DNA damage induced by nicotine and its mechanisms. Specimens of human nasal mucosa were harvested during surgery of the nasal air passage. After enzymatic digestion over night, single cells were exposed to an increasing nicotine concentration between 0.001 mM and 4.0mM. In a second step co-incubation was performed using the antioxidant N-acetylcysteine (NAC) and the nAChR antagonist mecamylamine. DNA damage was assessed using the alkali version of the comet assay. Dose finding experiments for mecamylamine to evaluate the maximal inhibitory effect were performed in the human bronchial cell line BEAS-2B with an increasing mecamylamine concentration and a constant nicotine concentration. The influence of nicotine in the apoptotic pathway was evaluated in BEAS-2B cells with the TUNEL assay combined with flow cytometry. After 1h of nicotine exposure with 0.001, 0.01, 0.1, 1.0 and 4.0mM, significant DNA damage was determined at 1.0mM. Further co-incubation experiments with mecamylamine and NAC were performed using 1.0mM of nicotine. The strongest inhibitory effect was measured at 1.0mM mecamylamine and this concentration was used for co-incubation. Both, the antioxidant NAC at a concentration of 1.0mM, based on the literature, as well as the receptor antagonist were capable of complete inhibition of the nicotine-induced DNA migration in the comet assay. A nicotine-induced increase or decrease in

Silver acetate interactions with nicotine and non-nicotine smoke components.

PubMed

Rose, Jed E; Behm, Frédérique M; Murugesan, Thangaraju; McClernon, F Joseph

2010-12-01

Oral topical silver-containing formulations were marketed in the 1970s and 1980s as smoking deterrents, based on the finding that when using such formulations, an unpleasant taste occurs upon smoking. This approach has not been widely adopted, however, in part because of a lack of efficacy data. The advent of new pharmacologic treatments for smoking cessation renews the possibility that such a taste aversion approach may be a useful adjunct to smoking cessation treatment. This study explored the basic mechanistic question of whether topical oral silver acetate solution interacts with nicotine as opposed to non-nicotine smoke constituents. We recruited 20 smoking volunteers to rate nicotine-containing or denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of puffs after rinsing their mouths with either silver acetate solution or deionized water (placebo). Silver acetate relative to placebo solution substantially reduced liking and satisfaction ratings for the usual brand and denicotinized cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected by the silver-based treatment. These results support the conclusion that silver acetate not only renders the taste of cigarette smoke less appealing, but also that the compound appears to interact selectively with non-nicotine smoke constituents. Moreover, these data suggest silver acetate would be compatible with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined use of taste aversion with nicotine replacement therapy could provide the smoker with additional assistance to resist relapse. Further exploration is warranted of the use of silver-based preparations as a short-term adjunct to smoking cessation treatment. PsycINFO Database Record (c) 2010 APA, all rights reserved.

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

PubMed Central

Saylor, Kyle; Zhang, Chenming

2017-01-01

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies’ ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. PMID:27473014

Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic receptor.

PubMed

Verbitsky, M; Rothlin, C V; Katz, E; Elgoyhen, A B

2000-10-01

The rat alpha9 nicotinic acetylcholine receptor (nAChR) was expressed in Xenopus laevis oocytes and tested for its sensitivity to a wide variety of cholinergic compounds. Acetylcholine (ACh), carbachol, choline and methylcarbachol elicited agonist-evoked currents, giving maximal or near maximal responses. Both the nicotinic agonist suberyldicholine as well as the muscarinic agonists McN-A-343 and methylfurtrethonium behaved as weak partial agonists of the receptor. Most classical cholinergic compounds tested, being either nicotinic (nicotine, epibatidine, cytisine, methyllycaconitine, mecamylamine, dihydro-beta-erythroidine), or muscarinic (muscarine, atropine, gallamine, pilocarpine, bethanechol) agonists and antagonists, blocked the recombinant alpha9 receptor. Block by nicotine, epibatidine, cytisine, methyllycaconitine and atropine was overcome at high ACh concentrations, suggesting a competitive type of block. The present results indicate that alpha9 displays mixed nicotinic-muscarinic features that resemble the ones described for the cholinergic receptor of cochlear outer hair cells (OHCs). We suggest that alpha9 contains the structural determinants responsible for the pharmacological properties of the native receptor.

Electronic Cigarettes and Indoor Air Quality: A Simple Approach to Modeling Potential Bystander Exposures to Nicotine

PubMed Central

Colard, Stéphane; O’Connell, Grant; Verron, Thomas; Cahours, Xavier; Pritchard, John D.

2014-01-01

There has been rapid growth in the use of electronic cigarettes (“vaping”) in Europe, North America and elsewhere. With such increased prevalence, there is currently a debate on whether the aerosol exhaled following the use of e-cigarettes has implications for the quality of air breathed by bystanders. Conducting chemical analysis of the indoor environment can be costly and resource intensive, limiting the number of studies which can be conducted. However, this can be modelled reasonably accurately based on empirical emissions data and using some basic assumptions. Here, we present a simplified model, based on physical principles, which considers aerosol propagation, dilution and extraction to determine the potential contribution of a single puff from an e-cigarette to indoor air. From this, it was then possible to simulate the cumulative effect of vaping over time. The model was applied to a virtual, but plausible, scenario considering an e-cigarette user and a non-user working in the same office space. The model was also used to reproduce published experimental studies and showed good agreement with the published values of indoor air nicotine concentration. With some additional refinements, such an approach may be a cost-effective and rapid way of assessing the potential exposure of bystanders to exhaled e-cigarette aerosol constituents. PMID:25547398

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saylor, Kyle, E-mail: saylor@vt.edu; Zhang, Chenmi

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down intomore » different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. - Highlights: • Modelling of nicotine disposition in the presence of anti-nicotine antibodies • Key vaccine efficacy factors are evaluated in silico in rats and in humans. • Model predicts insufficient antibody binding in past human nicotine vaccines. • Improving immunogenicity and antibody specificity may lead to vaccine success.« less

Sensory Effects of Menthol and Nicotine in an E-Cigarette

PubMed Central

Rosbrook, Kathryn

2016-01-01

Introduction: Despite the longstanding use and popularity of menthol as a flavorant in tobacco products, its sensory interactions with inhaled nicotine have never been measured independently of the other irritants in tobacco smoke. We therefore measured the perception of menthol in an E-cigarette with the primary goal of assessing its analgesic effect on the sensory irritation produced by inhaled nicotine. Methods: Adult cigarette smokers sampled aerosolized E-liquids containing five different concentrations of nicotine with 0%, 0.5%, or 3.5% l-menthol, as well as two commercial menthol flavors with and without nicotine. For each of the E-liquids participants used a labeled magnitude scale to rate the Overall Sensation intensity, Coolness/Cold, and Irritation/Harshness they experienced, and a Labeled Hedonic Scale to indicate how much they liked/disliked the overall flavor. Results: The main findings were that (1) perceived Irritation/Harshness was unaffected by a low (0.5%) menthol concentration, whereas a high menthol concentration (3.5%) led to higher perceived Irritation/Harshness at low nicotine concentrations but to lower Irritation/Harshness at the highest nicotine concentration (24mg/ml); (2) a commercial Menthol–Mint flavor produced similar results; (3) nicotine tended to enhance rather than suppress sensations of Coolness/Cold; and (4) menthol tended to slightly increase liking independently of nicotine concentration. Conclusion: In addition to adding a sensation of coolness, menthol can reduce perceived airway irritation and harshness produced by inhalation when nicotine concentration is high, and contributes to the sensory impact of E-liquids when nicotine concentration is low. Implications: The evidence presented here indicates that menthol can potentially improve the appeal of E-cigarettes not only via its coolness and minty flavor, but also by reducing the harshness from high concentrations of nicotine. As the first direct demonstration of an

Preadolescent tobacco smoke exposure leads to acute nicotine dependence but does not affect the rewarding effects of nicotine or nicotine withdrawal in adulthood in rats.

PubMed

Yamada, Hidetaka; Bishnoi, Mahendra; Keijzers, Kim F M; van Tuijl, Irma A; Small, Elysia; Shah, Hina P; Bauzo, Rayna M; Kobeissy, Firas H; Sabarinath, Sreedharan N; Derendorf, Hartmut; Bruijnzeel, Adrie W

2010-06-01

Epidemiological studies indicate that parental smoking increases the risk for smoking in children. However, the underlying mechanisms by which parental smoking increases the risk for smoking are not known. The aim of these studies was to investigate if preadolescent tobacco smoke exposure, postnatal days 21-35, affects the rewarding effects of nicotine and nicotine withdrawal in adult rats. The rewarding effects of nicotine were investigated with the conditioned place preference procedure. Nicotine withdrawal was investigated with the conditioned place aversion procedure and intracranial self-stimulation (ICSS). Elevations in brain reward thresholds in the ICSS paradigm reflect a dysphoric state. Plasma nicotine and cotinine levels in the preadolescent rats immediately after smoke exposure were 188 ng/ml and 716 ng/ml, respectively. Preadolescent tobacco smoke exposure led to the development of nicotine dependence as indicated by an increased number of mecamylamine-precipitated somatic withdrawal signs in the preadolescent tobacco smoke exposed rats compared to the control rats. Nicotine induced a similar place preference in adult rats that had been exposed to tobacco smoke or air during preadolescence. Furthermore, mecamylamine induced place aversion in nicotine dependent rats but there was no effect of preadolescent tobacco smoke exposure. Finally, preadolescent tobacco smoke exposure did not affect the elevations in brain reward thresholds associated with precipitated or spontaneous nicotine withdrawal. These studies indicate that passive exposure to tobacco smoke during preadolescence leads to the development of nicotine dependence but preadolescent tobacco smoke exposure does not seem to affect the rewarding effects of nicotine or nicotine withdrawal in adulthood. Published by Elsevier Inc.

Sensory Effects of Menthol and Nicotine in an E-Cigarette.

PubMed

Rosbrook, Kathryn; Green, Barry G

2016-07-01

Despite the longstanding use and popularity of menthol as a flavorant in tobacco products, its sensory interactions with inhaled nicotine have never been measured independently of the other irritants in tobacco smoke. We therefore measured the perception of menthol in an E-cigarette with the primary goal of assessing its analgesic effect on the sensory irritation produced by inhaled nicotine. Adult cigarette smokers sampled aerosolized E-liquids containing five different concentrations of nicotine with 0%, 0.5%, or 3.5% l-menthol, as well as two commercial menthol flavors with and without nicotine. For each of the E-liquids participants used a labeled magnitude scale to rate the Overall Sensation intensity, Coolness/Cold, and Irritation/Harshness they experienced, and a Labeled Hedonic Scale to indicate how much they liked/disliked the overall flavor. The main findings were that (1) perceived Irritation/Harshness was unaffected by a low (0.5%) menthol concentration, whereas a high menthol concentration (3.5%) led to higher perceived Irritation/Harshness at low nicotine concentrations but to lower Irritation/Harshness at the highest nicotine concentration (24mg/ml); (2) a commercial Menthol-Mint flavor produced similar results; (3) nicotine tended to enhance rather than suppress sensations of Coolness/Cold; and (4) menthol tended to slightly increase liking independently of nicotine concentration. In addition to adding a sensation of coolness, menthol can reduce perceived airway irritation and harshness produced by inhalation when nicotine concentration is high, and contributes to the sensory impact of E-liquids when nicotine concentration is low. The evidence presented here indicates that menthol can potentially improve the appeal of E-cigarettes not only via its coolness and minty flavor, but also by reducing the harshness from high concentrations of nicotine. As the first direct demonstration of an analgesic effect of menthol on inhaled nicotine in humans, these

Transdermal nicotine absorption handling e-cigarette refill liquids.

PubMed

Maina, Giovanni; Castagnoli, Carlotta; Passini, Valter; Crosera, Matteo; Adami, Gianpiero; Mauro, Marcella; Filon, Francesca Larese

2016-02-01

The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids. Copyright © 2015 Elsevier Inc. All rights reserved.

Air Data - Concentration Map

EPA Pesticide Factsheets

Make a map of daily concentrations over several days. The daily air quality can be displayed in terms of the Air Quality Index or in concentration ranges for certain PM species like organic carbon, nitrates, and sulfates.

Bioelectronic sniffer for nicotine using enzyme inhibition.

PubMed

Mitsubayashi, Kohji; Nakayama, Kazumi; Taniguchi, Midori; Saito, Hirokazu; Otsuka, Kimio; Kudo, Hiroyuki

2006-07-28

A novel bioelectronic sniffer for nicotine in the gas phase was developed with enzyme inhibition principle to butyrylcholinesterase activity. The bioelectronic devices for nicotine in the gas and liquid phases were constructed using a Clark-type dissolved oxygen electrode and a membrane immobilized butyrylcholinesterase and choline oxidase. After the assessment of the sensor performances to choline and butyrylcholine as pre-examinations, the characteristics of the biosensor and bio-sniffer for nicotine were evaluated in the liquid and gas phases, respectively. The sensor signal of the bio-devices with 300 micromol l(-1) of butyrylcholine decreased quickly following application of nicotine and reached to the steady-state current, thus relating the concentration of nicotine in the liquid and gas phases. The biosensor was used to measure nicotine solution from 10 to 300 micromol l(-1). In the gas-phase experiment, the current signal of the bio-sniffer was also found to be linearly to the nicotine concentration over the range of 10.0-1000 ppb including 75.0 ppb as threshold limit value (TLV) by American Conference of Governmental Industrial Hygienists (ACGIH).

Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats

PubMed Central

Pravetoni, M; Keyler, DE; Raleigh, MD; Harris, AC; LeSage, MG; Mattson, CK; Pettersson, S; Pentel, PR

2011-01-01

Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 minute nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a two hour whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular midday smoking. Vaccination prior to 10 min smoke NSE reduced nicotine distribution to brain by 90%, comparable to its effect on nicotine administered i.v. Vaccination prior to 2 hr smoke WBE reduced nicotine distribution to brain by 35%. The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 hr WBE was increased by 230% in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21–25% of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation. PMID:21333633

Unraveling the concentration-dependent metabolic response of Pseudomonas sp. HF-1 to nicotine stress by ¹H NMR-based metabolomics.

PubMed

Ye, Yangfang; Wang, Xin; Zhang, Limin; Lu, Zhenmei; Yan, Xiaojun

2012-07-01

Nicotine can cause oxidative damage to organisms; however, some bacteria, for example Pseudomonas sp. HF-1, are resistant to such oxidative stress. In the present study, we analyzed the concentration-dependent metabolic response of Pseudomonas sp. HF-1 to nicotine stress using ¹H NMR spectroscopy coupled with multivariate data analysis. We found that the dominant metabolites in Pseudomonas sp. HF-1 were eight aliphatic organic acids, six amino acids, three sugars and 11 nucleotides. After 18 h of cultivation, 1 g/L nicotine caused significant elevation of sugar (glucose, trehalose and maltose), succinate and nucleic acid metabolites (cytidine, 5'-CMP, guanine 2',3'-cyclic phosphate and adenosine 2',3'-cyclic phosphate), but decrease of glutamate, putrescine, pyrimidine, 2-propanol, diethyl ether and acetamide levels. Similar metabolomic changes were induced by 2 g/L nicotine, except that no significant change in trehalose, 5'-UMP levels and diethyl ether were found. However, 3 g/L nicotine led to a significant elevation in the two sugars (trehalose and maltose) levels and decrease in the levels of glutamate, putrescine, pyrimidine and 2-propanol. Our findings indicated that nicotine resulted in the enhanced nucleotide biosynthesis, decreased glucose catabolism, elevated succinate accumulation, severe disturbance in osmoregulation and complex antioxidant strategy. And a further increase of nicotine level was a critical threshold value that triggered the change of metabolic flow in Pseudomonas sp. HF-1. These findings revealed the comprehensive insights into the metabolic response of nicotine-degrading bacteria to nicotine-induced oxidative toxicity.

Nicotine as a Marker for Environmental Tobacco Smoke: Implications of Sorption on Indoor Surface Materials.

PubMed

Van Loy, Michael D; Nazaroff, William W; Daisey, Joan M

1998-10-01

Recently developed models and data describing the interactions of gas-phase semi-volatile organic compounds with indoor surfaces are employed to examine the effects of sorption on nicotine's suitability as an environmental tobacco smoke (ETS) marker. Using parameters from our studies of nicotine sorption on carpet, painted wallboard, and stainless steel and previously published data on ETS particle deposition, the dynamic behavior of nicotine was modeled in two different indoor environments: a house and a stainless steel chamber. The results show that apparently contradictory observations of nicotine's behavior in indoor air can be understood by considering the effects of sorption under different experimental conditions. In indoor environments in which smoking has occurred regularly for an extended period, the sorbed mass of nicotine is very large relative to the mass emitted by a single cigarette. The importance of nicotine adsorption relative to ventilation as a gas-phase removal mechanism is reduced. Where smoking occurs less regularly or the indoor surfaces are cleaned prior to smoking (as in a laboratory chamber), nicotine deposition is more significant. Nicotine concentrations closely track the levels of other ETS constituents in environments with habitual smoking if the data are averaged over a period significantly longer than the period between cigarette combustion episodes. However, nicotine is not a suitable tracer for predicting ETS exposures at fine time scales or in settings where smoking occurs infrequently and irregularly.

Delivery of nicotine aerosol to mice via a modified electronic cigarette device

PubMed Central

Lefever, Timothy W.; Lee, Youn O.K.; Kovach, Alexander L.; Silinski, Melanie A.R.; Marusich, Julie A.; Thomas, Brian F.; Wiley, Jenny L.

2017-01-01

Background Although both men and women use e-cigarettes, most preclinical nicotine research has focused on its effects in male rodents following injection. The goals of the present study were to develop an effective e-cigarette nicotine delivery system, to compare results to those obtained after subcutaneous (s.c.) injection, and to examine sex differences in the model. Methods Hypothermia and locomotor suppression were assessed following aerosol exposure or s.c. injection with nicotine in female and male mice. Subsequently, plasma and brain concentrations of nicotine and cotinine were measured. Results Passive exposure to nicotine aerosol produced concentration-dependent and mecamylamine reversible hypothermic and locomotor suppressant effects in female and male mice, as did s.c. nicotine injection. In plasma and brain, nicotine and cotinine concentrations showed dose/concentration-dependent increases in both sexes following each route of administration. Sex differences in nicotine-induced hypothermia were dependent upon route of administration, with females showing greater hypothermia following aerosol exposure and males showing greater hypothermia following injection. In contrast, when they occurred, sex differences in nicotine and cotinine levels in brain and plasma consistently showed greater concentrations in females than males, regardless of route of administration. Discussion In summary, the e-cigarette exposure device described herein was used successfully to deliver pharmacologically active doses of nicotine to female and male mice. Further, plasma nicotine concentrations following exposure were similar to those after s.c. injection with nicotine and within the range observed in human smokers. Future research on vaped products can be strengthened by inclusion of translationally relevant routes of administration. PMID:28157590

Dynamic behavior of semivolatile organic compounds in indoor air. 2. Nicotine and phenanthrene with carpet and wallboard.

PubMed

Van Loy, M D; Riley, W J; Daisey, J M; Nazaroff, W W

2001-02-01

The surface interactions of nicotine and phenanthrene with carpet, painted wallboard, and stainless steel were investigated in a room-sized environmental test chamber. Adsorption kinetics were tested by flash evaporating a known mass of each compound into a sealed 20 m3 chamber containing one or more of the tested sorbents. In each experiment, one or more emissions were performed after the gas-phase concentration had reached an apparent plateau. At the end of each experiment, the chamber was ventilated and resealed to monitor reemission of the compound from the sorbents. Kinetic sorption parameters were determined by fitting a mass-balance model to the experimental results. The sorption capacity of stainless steel was of similar magnitude for nicotine and phenanthrene. Sorption of nicotine on carpet and wallboard was much stronger, with equilibrium partitioning values 2-3 orders of magnitude higher. The sorption capacities of phenanthrene on carpet and wallboard were smaller, approximately 10-20% of the stainless steel values. The rates of uptake are of similar magnitude for all sorbate--sorbent pairs and are consistent with the limit imposed by gas-phase boundary-layer mass transport. The rates of desorption are much faster for phenanthrene than for nicotine. Model simulations predict average nicotine levels in a typical smoking residence that are consistent with published data.

Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delijewski, Marcin; Beberok, Artur; Otręba, Michał

Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC{sub 50} was determined to be 7.43 mM. Nicotine inhibited a melanizationmore » process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress.« less

Use of nicotine patches in breast-feeding mothers: transfer of nicotine and cotinine into human milk.

PubMed

Ilett, Kenneth F; Hale, Thomas W; Page-Sharp, Madhu; Kristensen, Judith H; Kohan, Rolland; Hackett, L Peter

2003-12-01

Our objective was to assess the extent of exposure to nicotine and cotinine in breast-fed infants during maternal smoking and later during maternal use of the nicotine transdermal patch to achieve smoking cessation. Fifteen lactating women (mean age, 32 years; mean weight, 72 kg) who were smokers (mean of 17 cigarettes per day) participated in a trial of the nicotine patch to assist in smoking cessation. Serial milk samples were collected from the women over sequential 24-hour periods when they were smoking and when they were stabilized on the 21-mg/d, 14-mg/d, and 7-mg/d nicotine patches. Nicotine and cotinine in milk were quantified by HPLC, and infant dose was calculated. Plasma concentrations of nicotine in the breast-fed infants were assessed, and the infants were also clinically assessed. Nicotine and cotinine concentrations in milk were not significantly different between smoking (mean of 17 cigarettes per day) and the 21-mg/d patch, but concentrations were significantly lower (P <.05) when patients were using the 14-mg/d and 7-mg/d patches than when smoking. There was also a downward trend in absolute infant dose (nicotine equivalents) from smoking or the 21-mg patch through to the 14-mg and 7-mg patches (P <.05 at both 14-mg and 7-mg doses, compared with smoking). Milk intake (shown as median and 25th to 75th percentile) by the breast-fed infants was similar while their mothers were smoking (585 mL/d [507-755 mL/d]) and subsequently when their mothers were using the 21-mg (717 mL/d [504-776 mL/d]), 14-mg (731 mL/d [535-864 mL/d]), and 7-mg (619 mL/d [520-706 mL/d]) patches (chi(2) = 3.19, P =.364). We conclude that the absolute infant dose of nicotine and its metabolite cotinine decreases by about 70% from when subjects were smoking or using the 21-mg patch to when they were using the 7-mg patch. In addition, use of the nicotine patch had no significant influence on the milk intake by the breast-fed infant. Undertaking maternal smoking cessation with the

Flavorings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS)

PubMed Central

Leigh, Noel J.; Lawton, Ralph I.; Hershberger, Pamela A.; Goniewicz, Maciej L.

2018-01-01

Background E-cigarettes or electronic nicotine delivery systems (ENDS) are designed to deliver nicotine-containing aerosol via inhalation. Little is known about the health effects of flavored ENDS aerosol when inhaled. Methods Aerosol from ENDS was generated using a smoking-machine. Various types of ENDS devices or a tank system prefilled with liquids of different flavors, nicotine carrier, variable nicotine concentrations, and with modified battery output voltage were tested. A convenience sample of commercial fluids with flavor names of tobacco, piña colada, menthol, coffee and strawberry were used. Flavoring chemicals were identified using gas chromatography/mass spectrometry. H292 human bronchial epithelial cells were directly exposed to 55 puffs of freshly-generated ENDS aerosol, tobacco smoke, or air (controls) using an air-liquid interface system and the Health Canada intense smoking protocol. The following in vitro toxicological effects were assessed: 1) cell viability, 2) metabolic activity and 3) release of inflammatory mediators (cytokines). Results Exposure to ENDS aerosol resulted in decreased metabolic activity and cell viability and increased release of IL-1β, IL-6, IL-10, CXCL1, CXCL2 and CXCL10 compared to air controls. Cell viability and metabolic activity were more adversely affected by conventional cigarettes than most tested ENDS products. Product type, battery output voltage, and flavors significantly affected toxicity of ENDS aerosol, with a strawberry-flavored product being the most cytotoxic. Conclusions Our data suggest that characteristics of ENDS products, including flavors, may induce inhalation toxicity. Therefore, ENDS users should use the products with caution until more comprehensive studies are performed. PMID:27633767

Delivery of nicotine aerosol to mice via a modified electronic cigarette device.

PubMed

Lefever, Timothy W; Lee, Youn O K; Kovach, Alexander L; Silinski, Melanie A R; Marusich, Julie A; Thomas, Brian F; Wiley, Jenny L

2017-03-01

Although both men and women use e-cigarettes, most preclinical nicotine research has focused on its effects in male rodents following injection. The goals of the present study were to develop an effective e-cigarette nicotine delivery system, to compare results to those obtained after subcutaneous (s.c.) injection, and to examine sex differences in the model. Hypothermia and locomotor suppression were assessed following aerosol exposure or s.c. injection with nicotine in female and male mice. Subsequently, plasma and brain concentrations of nicotine and cotinine were measured. Passive exposure to nicotine aerosol produced concentration-dependent and mecamylamine reversible hypothermic and locomotor suppressant effects in female and male mice, as did s.c. nicotine injection. In plasma and brain, nicotine and cotinine concentrations showed dose/concentration-dependent increases in both sexes following each route of administration. Sex differences in nicotine-induced hypothermia were dependent upon route of administration, with females showing greater hypothermia following aerosol exposure and males showing greater hypothermia following injection. In contrast, when they occurred, sex differences in nicotine and cotinine levels in brain and plasma consistently showed greater concentrations in females than males, regardless of route of administration. In summary, the e-cigarette exposure device described herein was used successfully to deliver pharmacologically active doses of nicotine to female and male mice. Further, plasma nicotine concentrations following exposure were similar to those after s.c. injection with nicotine and within the range observed in human smokers. Future research on vaped products can be strengthened by inclusion of translationally relevant routes of administration. Copyright © 2017 Elsevier B.V. All rights reserved.

Nicotine and Cotinine Levels With Electronic Cigarette: A Review.

PubMed

Marsot, A; Simon, N

2016-01-01

Since their introduction in 2004, electronic cigarettes (e-cigarettes) have gained popularity worldwide. E-cigarettes are marketed as nicotine delivery devices. Commonly reported reasons for use include to quit smoking, to reduce urge to smoke, or the perceived lower risk alternative to smoking. But what are the actual amounts of nicotine delivered? This review summarizes all the published studies concerning nicotine or cotinine levels following e-cigarette use. A literature search was conducted from the PubMed database, from 1985 to January 2014, using the following terms: electronic cigarette(s), e-cigarette(s), electronic nicotine delivery system, cotinine, and nicotine. Articles were excluded if they were not pertinent according to our criteria. References of all relevant articles were also evaluated. Eight studies were included in this review. The following information was extracted from the articles: population size, age of participants, recruitment, inclusion and exclusion criteria, concentration of nicotine in refills liquids, study sample design, and observed concentrations. Following design of studies, plasma nicotine Cmax was observed between 0 and 5 ng/mL (no significant changes) or between 13.9 and 16.3 ng/mL (similar to a tobacco cigarette) with a Tmax between 70 and 75 minutes. Cotinine levels after "vaping" an e-cigarette are similar to a tobacco cigarette. This review summarizes e-cigarette studies that contain information on nicotine or cotinine levels. The peak concentration of nicotine appears to be dependent on the use and dose level of e-cigarette cartridge. The value of this peak concentration is similar to the value found with a tobacco cigarette. However, the time corresponding to the peak concentration is delayed compared to a tobacco cigarette. © The Author(s) 2015.

Biodegradation of nicotine by a newly isolated Pseudomonas stutzeri JZD

NASA Astrophysics Data System (ADS)

Petricevic, Jelena; Gujanicic, Vera; Radic, Danka; Jovicic Petrovic, Jelena; Jovic, Jelena; Raicevic, Vera

2013-04-01

The tobacco-manufacturing process and all activities that use tobacco, produce solid or liquid wastes with high concentrations of nicotine. Nicotine is a significant toxic waste product in tobacco industry. This waste is classified as 'toxic and hazardous' by European Union regulations when the nicotine content exceeds 500 milligrams per kilogram dry weight. Therefore, there is a major environmental requirement to remove nicotine from tobacco wastes. Bioremediation techniques which involve nicotine degradation by microorganisms have attracted attention during the last years, because microorganisms have the potential to reduce nicotine levels in tobacco and to detoxify tobacco wastes. The aim of this study is isolation and identification of nicotine degraded bacteria and optimization of nicotine degradation in laboratory conditions. An aerobic bacterial strain capable of effectively degrading nicotine was isolated from the tobacco industry waste, Serbia. After isolation, the liquid culture was spread onto the solid plates of the nicotine inorganic salt medium using the dilution plate method. Cell morphology of strain was observed by a light microscope and physiological characteristics were determined by Api technique and sequence analyzes of 16S rDNA. This isolate was identified as Pseudomonas stutzeri based on morphology, physiological characteristics, and Apiweb technique. Comparison with sequences available in data library showed the 99% similarity with 16S rDNA gene sequence of the species Pseudomonas stutzeri ( GenBank Acc. No. CP003725). We analyzed the effect of initial nicotine concentration (1g/L, 1.5 g/L, 2.5 g/L) on microbial activity in aim to optimize biodegradation. The effect of cultivation temperature (25°C; 30°C; 37°C) on nicotine degradation by P. stutzeri was evaluated after 24 h of cultivation, with 1.5 g/L nicotine added as the sole carbon source. Effect of biodegradation has depended on initial concentration. During incubation, number of

Nicotine pharmacokinetics and its application to intake from smoking.

PubMed Central

Feyerabend, C; Ings, R M; Russel, M A

1985-01-01

Five subjects were given 25 micrograms/kg nicotine intravenously over 1 min, before and after a loading period involving the smoking of six cigarettes. Plasma nicotine concentrations declined in a biphasic manner, the half-lives of the initial and terminal phases averaging 9 min and 133 min respectively. Terminal half-lives before and after the loading period were essentially the same suggesting the absence of saturation kinetics at nicotine concentrations that build up during smoking. The plasma clearance of nicotine and the volume of distribution were very high averaging 915 ml/min and 1731, respectively. Two approaches were used to calculate the nicotine intake from smoking. The average dose of nicotine absorbed from one cigarette was 1.06 mg which was 82% of the standard machine-smoked yield of 1.3 mg. To illustrate their potential use in 'nicotine titration' studies, these approaches were used to compare nicotine intake from smoking a high (2.4 mg) and low (0.6 mg) nicotine cigarette. The dose of nicotine absorbed averaged 1.14 mg and 0.86 mg per cigarette respectively, being 48% and 143% of the machine-smoked yields. PMID:3986082

Observations on using inside air concentrations as a predictor of outside air concentrations

DOE PAGES

Hawkley, Gavin; Whicker, Jeffrey; Harris, Jason

2015-04-01

Here, excavations of radiological material were performed within confined structures with known operational parameters, such as a filtered exhaust system with known filtration efficiency. Given the known efficiency, the assumption could be made that the air concentrations of radioactivity measured outside the structure would be proportional to the air concentrations measured inside the structure. To investigate this assumption, the inside concentration data was compared with the outside concentration data. The correlation of the data suggested that the inside concentrations were not a good predictor of the outside concentrations. This poor correlation was deemed to be a result of operational unknownsmore » within the structures.« less

Inactivation gating determines nicotine blockade of human HERG channels.

PubMed

Wang, H Z; Shi, H; Liao, S J; Wang, Z

1999-09-01

We have previously found that nicotine blocked multiple K+ currents, including the rapid component of delayed rectifier K+ currents (IKr), by interacting directly with the channels. To shed some light on the mechanisms of interaction between nicotine and channels, we performed detailed analysis on the human ether-à-go-go-related gene (HERG) channels, which are believed to be equivalent to the native I(Kr) when expressed in Xenopus oocytes. Nicotine suppressed the HERG channels in a concentration-dependent manner with greater potency with voltage protocols, which favor channel inactivation. Nicotine caused dramatic shifts of the voltage-dependent inactivation curve to more negative potentials and accelerated the inactivation process. Conversely, maneuvers that weakened the channel inactivation gating considerably relieved the blockade. Elevating the extracellular K+ concentration from 5 to 20 mM increased the nicotine concentration (by approximately 100-fold) needed to achieve the same degree of inhibition. Moreover, nicotine lost its ability to block the HERG channels when a single mutation was introduced to a residue located after transmembrane domain 6 (S631A) to remove the rapid channel inactivation. Our data suggest that the inactivation gating determines nicotine blockade of the HERG channels.

Clinical outcome of smoking-cessation trial of nicotine chewing gum evaluated by analysis of nicotine in hair.

PubMed

Mizuno, A; Uematsu, T; Ishikawa, T; Yoshimine, N; Nakashima, M

1997-08-01

The axial distribution of nicotine along the hair shafts was examined in 21 subjects enrolled in a placebo-controlled, double-blind trial of nicotine chewing gum (Nicorette) for validating their self-reported smoking behavior and their physicians' assessments. Hair samples obtained from the subjects once during the 3-month follow-up period (n = 10 for placebo and n = 11 for Nicorette ad libitum) were analyzed for the cm x cm distribution of nicotine along the hair shafts. Hair analysis results were compared with the monthly self-reports and with the plasma concentrations of thiocyanate (SCN-) measured at 1-month intervals. A gradual decrease in nicotine content along the hair shafts generally corresponded to the decrease in self-reported number of cigarettes smoked daily by the subjects who reported that they abstained from smoking or decreased the number of daily cigarettes in placebo and nicotine chewing gum groups. Because nicotine may dissociate slowly from hair follicle cells, nicotine in the hair did not mark a sudden decrease or cessation of smoking and, therefore, hair analysis tended to underestimate the real decrease of smoking. However, physician assessment seemed to depend solely on self-reporting because the time profile of changes in serum SCN- concentration did not correspond necessarily to the changes in the self-reported number of cigarettes used daily.

Surveillance of moist snuff: total nicotine, moisture, pH, un-ionized nicotine, and tobacco-specific nitrosamines.

PubMed

Richter, Patricia; Hodge, Knachelle; Stanfill, Stephen; Zhang, Liqin; Watson, Clifford

2008-11-01

In 2005, approximately 2.3% of U.S. adults used smokeless tobacco. Moist snuff leads all types of smokeless tobacco in revenues and marketing expenditures. The U.S. Surgeon General has concluded that smokeless tobacco use can lead to nicotine addiction. The National Toxicology Program of the National Institutes of Health has classified smokeless tobacco as a human carcinogen. Tobacco-specific nitrosamines (TSNAs) are potent carcinogens in smokeless tobacco products, and the pH of the product influences the content of un-ionized nicotine which is the form of nicotine most rapidly absorbed in the mouth. The Centers for Disease Control and Prevention analyzed 40 top-selling brands of moist snuff to measure nicotine, moisture, pH, un-ionized nicotine, and TSNAs, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The study findings indicate that moist snuff brands varied widely in content of rapidly absorbed, addictive un-ionized nicotine (500-fold range) and of carcinogenic TSNAs (18-fold range). Product characteristics such as packaging and moisture content appeared to be correlated with concentrations of un-ionized nicotine, and flavor characteristics of low-priced brands may correlate with TSNA concentrations. These findings warrant further study in light of (a) the marketing of smokeless tobacco for use in places where smoking is prohibited, (b) the promotion of smokeless tobacco as a harm-reduction product, and (c) the ever-expanding number of highly flavored smokeless varieties brought to the market.

Electronic Cigarette Nicotine Delivery Can Exceed that of Combustible Cigarettes: A Preliminary Report

PubMed Central

Ramôa, Carolina P.; Hiler, Marzena M.; Spindle, Tory R; Lopez, Alexa A.; Karaoghlanian, Nareg; Lipato, Thokozeni; Breland, Alison B.; Shihadeh, Alan; Eissenberg, Thomas

2016-01-01

Introduction Electronic cigarettes (ECIGs) aerosolize a liquid that usually contains propylene glycol and/or vegetable glycerin, flavorants, and the dependence-producing drug nicotine in various concentrations. This laboratory study examined the relationship between liquid nicotine concentration on plasma nicotine concentration and puffing behavior in experienced ECIG users. Methods Sixteen ECIG-experienced participants used a 3.3-Volt ECIG battery attached to a 1.5-Ohm dual-coil “cartomizer” loaded with 1 ml of a flavored propylene glycol/vegetable glycerin liquid to complete four sessions, at least 2 days apart, that differed by nicotine concentration (0, 8, 18, or 36 mg/ml). In each session, participants completed two 10-puff ECIG use bouts (30-sec puff interval) separated by 60 minutes. Venous blood was sampled to determine plasma nicotine concentration. Puff duration, volume, and average flow rate were measured. Results Immediately after bout 1, mean plasma nicotine concentration was 5.5 ng/ml (SD=7.7) for 0 mg/ml liquid, with significantly (p<0.05) higher mean concentrations observed for the 8 (mean=17.8 ng/ml, SD=14.6), 18 (mean=25.9 ng/ml, SD=17.5), and 36 mg/ml (mean=30.2 ng/ml; SD=20.0) concentrations; a similar pattern was observed for bout 2. For bout 1, at 36 mg/ml, the mean post- minus pre-bout difference was 24.1 ng/ml (SD=18.3). Puff topography data were consistent with previous results and revealed few reliable differences across conditions. Discussion This study demonstrates a relationship between ECIG liquid nicotine concentration and user plasma nicotine concentration in experienced ECIG users. Nicotine delivery from some ECIGs may exceed that of a combustible cigarette. The rationale for this higher level of nicotine delivery is uncertain. PMID:26324250

Effects of nicotine-containing and "nicotine-free" e-cigarette refill liquids on intracranial self-stimulation in rats.

PubMed

Harris, Andrew C; Muelken, Peter; Smethells, John R; Yershova, Katrina; Stepanov, Irina; Olson, Thao Tran; Kellar, Kenneth J; LeSage, Mark G

2018-04-01

Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported that an EC refill liquid produced less aversive/anhedonic effects at a high nicotine dose than nicotine alone as measured by elevations in intracranial self-stimulation (ICSS) thresholds, which may reflect the presence of behaviorally active non-nicotine constituents (e.g., propylene glycol) in the EC liquids. The primary objective of this study was to assess the generality of our prior ICSS findings to two additional EC liquids. We also compared effects of "nicotine-free" varieties of these EC liquids on ICSS, as well as binding affinity and/or functional activity of nicotine alone, nicotine-containing EC liquids, and "nicotine-free" EC liquids at nicotinic acetylcholine receptors (nAChRs). Nicotine alone and nicotine dose-equivalent concentrations of both nicotine-containing EC liquids produced similar lowering of ICSS thresholds at low to moderate nicotine doses, indicating similar reinforcement-enhancing effects. At high nicotine doses, nicotine alone elevated ICSS thresholds (a measure of anhedonia-like behavior) while the EC liquids did not. Nicotine-containing EC liquids did not differ from nicotine alone in terms of binding affinity or functional activity at nAChRs. "Nicotine-free" EC liquids did not affect ICSS, but bound with low affinity at some (e.g., α4ß2) nAChRs. These findings suggest that non-nicotine constituents in these EC liquids do not contribute to their reinforcement-enhancing effects. However, they may attenuate nicotine's acute aversive/anhedonic and/or toxic effects, which may moderate the abuse liability and/or toxicity of ECs. Copyright © 2018 Elsevier B.V. All rights reserved.

Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers.

PubMed

Brossard, Patrick; Weitkunat, Rolf; Poux, Valerie; Lama, Nicola; Haziza, Christelle; Picavet, Patrick; Baker, Gizelle; Lüdicke, Frank

2017-10-01

Two open-label randomized cross-over studies in Japanese smokers investigated the single-use nicotine pharmacokinetic profile of the Tobacco Heating System (THS) 2.2, cigarettes (CC) and nicotine replacement therapy (Gum). In each study, one on the regular and one on the menthol variants of the THS and CC, both using Gum as reference, 62 subjects were randomized to four sequences: Sequence 1: THS - CC (n = 22); Sequence 2: CC - THS (n = 22); Sequence 3: THS - Gum (n = 9); Sequence 4: Gum - THS (n = 9). Plasma nicotine concentrations were measured in 16 blood samples collected over 24 h after single use. Maximal nicotine concentration (C max ) and area under the curve from start of product use to time of last quantifiable concentration (AUC 0-last ) were similar between THS and CC in both studies, with ratios varying from 88 to 104% for C max and from 96 to 98% for AUC 0-last . Urge-to-smoke total scores were comparable between THS and CC. The THS nicotine pharmacokinetic profile was close to CC, with similar levels of urge-to-smoke. This suggests that THS can satisfy smokers and be a viable alternative to cigarettes for adult smokers who want to continue using tobacco. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Exposure to tobacco smoke before and after a partial smoking ban in prison: indoor air quality measures.

PubMed

Ritter, Catherine; Huynh, Cong Khanh; Etter, Jean-François; Elger, Bernice S

2012-09-01

Although exposure to secondhand smoke (SHS) is reportedly high in prison, few studies have measured this in the prison environment, and none have done so in Europe. We measured two indicators of SHS exposure (particulate matter PM10 and nicotine) in fixed locations before (2009) and after (2010) introduction of a partial smoking ban in a Swiss prison. Access to smoking cessation support was available to detainees throughout the study. To measure SHS before and after the introduction of a partial smoking ban. Assessment of particulate matter PM10 (suspended microparticles of 10 μm) and nicotine in ambient air, collected by real-time aerosol monitor and nicotine monitoring devices. The authors observed a significant improvement of nicotine concentrations in the air after the introduction of the smoking ban (before: 7.0 μg/m(3), after: 2.1 μg/m(3), difference 4.9 μg/m(3), 95% CI for difference: 0.52 to 9.8, p=0.03) but not in particulate matter PM10 (before: 0.11 mg/m(3), after: 0.06 mg/m(3), difference 0.06 mg/m(3), 95% CI for difference of means: -0.07 to 0.19, p=0.30). The partial smoking ban was followed by a decrease in nicotine concentrations in ambient air. These improvements can be attributed to the introduction of the smoking ban since no other policy change occurred during this period. Although this shows that concentrations of SHS decreased significantly, protection was still incomplete and further action is necessary to improve indoor air quality.

Nicotine dependence and psychiatric disorders.

PubMed

Salín-Pascual, Rafael J; Alcocer-Castillejos, Natasha V; Alejo-Galarza, Gabriel

2003-01-01

, concentration, and memory. Finally there are several strategies to deal with nicotine dependence, Nicotine Replacement Therapy (NRT), which are nicotine chewing-gum, transdermal nicotine patches, and nicotine inhalators device. Also some antidepressants like bupropion has shown to be effective in smoking cessation treatment. To know more about nicotine phenomenon would be important, because that will allow a more mature perspective about the damage and beneficial effects of that substance.

Sorption, desorption, and surface oxidative fate of nicotine.

PubMed

Petrick, Lauren; Destaillats, Hugo; Zouev, Irena; Sabach, Sara; Dubowski, Yael

2010-09-21

Nicotine dynamics in an indoor environment can be greatly affected by building parameters (e.g. relative humidity (RH), air exchange rate (AER), and presence of ozone), as well as surface parameters (e.g. surface area (SA) and polarity). To better understand the indoor fate of nicotine, these parameter effects on its sorption, desorption, and oxidation rates were investigated on model indoor surfaces that included fabrics, wallboard paper, and wood materials. Nicotine sorption under dry conditions was enhanced by higher SA and higher polarity of the substrate. Interestingly, nicotine sorption to cotton and nylon was facilitated by increased RH, while sorption to polyester was hindered by it. Desorption was affected by RH, AER, and surface type. Heterogeneous nicotine-ozone reaction was investigated by Fourier transform infrared spectrometry with attenuated total reflection (FTIR-ATR), and revealed a pseudo first-order surface reaction rate of 0.035 +/- 0.015 min(-1) (at [O(3)] = 6 +/- 0.3 x 10(15) molecules cm(-3)) that was partially inhibited at high RH. Extrapolation to a lower ozone level ([O(3)] = 42 ppb) showed oxidation on the order of 10(-5) min(-1) corresponding to a half-life of 1 week. In addition, similar surface products were identified in dry and high RH using gas chromatography-mass spectrometry (GC-MS). However, FTIR analysis revealed different product spectra for these conditions, suggesting additional unidentified products and association with surface water. Knowing the indoor fate of condensed and gas phase nicotine and its oxidation products will provide a better understanding of nicotine's impact on personal exposures as well as overall indoor air quality.

The effect of nicotine on reproduction and attachment of human gingival fibroblasts in vitro.

PubMed

Peacock, M E; Sutherland, D E; Schuster, G S; Brennan, W A; O'Neal, R B; Strong, S L; Van Dyke, T E

1993-07-01

The ability of fibroblasts to reproduce and attach to teeth is of paramount importance in re-establishing the lost connective tissue attachment after periodontal therapy. This study examined the effect of nicotine, a major component of the particulate phase of tobacco smoke, on human gingival fibroblast (HGF) reproduction and attachment to tissue culture surfaces. Pooled HGF cultures made from explants of gingival biopsies were utilized between passages 5 and 10 and plated in 96-well plates at 1.0 x 10(4) cells per well. Cell numbers were determined using 3-(4,5-dimethylthiazol-2-y)-2,5-diphenyl tetrazolium bromide (MTT), which is a reflection of mitochondrial dehydrogenase activity. The concentrations of nicotine used were 0.025, 0.05, 0.1, 0.2, and 0.4 microM, the average serum concentration for a smoker being approximately 0.1 microM. The effect of continuous nicotine exposure on HGF reproduction was determined by incubating cell cultures and media containing nicotine for up to 48 hours. Residual toxicity was determined by preincubating cells with nicotine for 1 or 6 hours. HGF suspensions and increasing concentrations of nicotine were added together to determine the effect on attachment. Results showed an enhanced effect of nicotine on HGF attachment, with increasing numbers of cells attaching with increasing nicotine concentrations, compared to the control. Low concentrations of nicotine had a stimulatory effect on cell replication, while higher concentrations of nicotine appear to have no significant effect on HGF reproduction. The responses of cells to some concentrations of nicotine may persist after its removal.

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges
.

PubMed

Sukhija, Manpreet; Srivastava, Reena; Kaushik, Aditya

2018-03-01

Nicotine replacement therapy (NRT) increases the probability of smoking cessation. This study was conducted to determine if three prototype 4-mg nicotine lozenges produced locally in India were bioequivalent to a globally marketed reference product, Nicorette® 4-mg nicotine lozenge. Healthy adult smokers (N = 39) were treated with three prototype 4-mg nicotine lozenges in comparison with a reference 4-mg lozenge in this single-center, randomized, open-label, single-dose, 4-way crossover study. Pharmacokinetic sampling was obtained to test for bioequivalence using maximal plasma concentration (Cmax) and extent of absorption (AUC0-t). Secondarily, AUC;0-∞, time to maximal plasma concentration (tmax), half-life (T1/2), elimination rate constant (Kel), and safety of the prototype lozenges versus the reference lozenge were compared. Each prototype 4-mg nicotine lozenge was found to be bioequivalent to the reference 4-mg nicotine lozenge based on the ratio of geometric means and 90% confidence intervals for Cmax, AUC0-t, and AUC;0-∞. Although tmax; was significantly longer for prototype III, all four lozenges achieved maximum plasma nicotine concentrations at a median of 1.5 hours. The safety profiles of the three prototype 4-mg lozenges did not differ from that of the 4-mg reference product. Each prototype 4-mg nicotine lozenge was bioequivalent to the reference 4-mg nicotine lozenge and was well tolerated. Furthermore, as these bioequivalent prototypes differed in in-vitro dissolution profiles, these data suggest that performance from the in -vitro method deployed is not a firm predictor of pharmacokinetic behavior.
.

Toxic potential of the emerging contaminant nicotine to the aquatic ecosystem.

PubMed

Oropesa, Ana Lourdes; Floro, António Miguel; Palma, Patrícia

2017-07-01

Nicotine is a "life-style compound" widely consumed by human populations and, consequently, often found in surface waters. This fact presents a concern for possible effects in the aquatic ecosystems. The objective of this study was to assess the potential lethal and sublethal toxicity of nicotine in aquatic organisms from different trophic levels (Vibrio fischeri, Pseudokirchneriella subcapitata, Thamnocephalus platyurus, and Daphnia magna). The bioassays were performed by exposing the organisms to concentrations of nicotine in a range of 0.5-1000 μg/L. Results showed that nicotine, at tested concentration, was not acutely toxic to V. fischeri and T. platyurus. On the contrary, this substance exhibited toxicity to P. subcapitata and Daphnia magna. Thus, concentrations of nicotine of 100 and 200 μg/L promoted an inhibition in the growth of P. subcapitata. In addition, a concentration of 100 μg/L nicotine acted on the reproduction of the crustacean D. magna, by decreasing the number of juveniles produced by female. On the other hand, the results showed that concentrations equal to or greater than 10 μg/L induced the production of daphnids male offspring, which may indicate that nicotine is a weak juvenoid compound of the D. magna endocrine system. Furthermore, the result showed that concentrations tested of this chemical have the capacity to revert the effect of fenoxycarb, a strong juvenoid chemical insecticide. The results of the study revealed that nicotine can induce several changes in some of the most important key groups of the aquatic compartment, which can compromise, in a short time, the balance of aquatic ecosystem. Finally, a preliminary environmental risk assessment of this stimulant was performed from the highest measured concentration in surface water and the no observable effect concentration value in the most sensitive species, i.e., D. magna. This process revealed that nicotine can produce an important risk to aquatic organisms.

21 CFR 172.310 - Aluminum nicotinate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be safely used as a source of niacin in foods for special dietary use. A statement of the concentration of the additive, expressed as niacin...

Detoxification and elimination of nicotine by nectar-feeding birds.

PubMed

Lerch-Henning, S; Du Rand, E E; Nicolson, S W

2017-05-01

Many dilute nectars consumed by bird pollinators contain secondary metabolites, potentially toxic chemicals produced by plants as defences against herbivores. Consequently, nectar-feeding birds are challenged not only by frequent water excess, but also by the toxin content of their diet. High water turnover, however, could be advantageous to nectar consumers by enabling them to excrete secondary metabolites or their transformation products more easily. We investigated how the alkaloid nicotine, naturally present in nectar of Nicotiana species, influences osmoregulation in white-bellied sunbirds Cinnyris talatala and Cape white-eyes Zosterops virens. We also examined the metabolic fate of nicotine in these two species to shed more light on the post-ingestive mechanisms that allow nectar-feeding birds to tolerate nectar nicotine. A high concentration of nicotine (50 µM) decreased cloacal fluid output and increased its osmolality in both species, due to reduced food intake that led to dehydration. White-eyes excreted a higher proportion of the ingested nicotine-containing diet than sunbirds. However, sugar concentration did not affect nicotine detoxification and elimination. Both species metabolised nicotine, excreting very little unchanged nicotine. Cape white-eyes mainly metabolised nicotine through the cotinine metabolic pathway, with norcotinine being the most abundant metabolite in the excreta, while white-bellied sunbirds excreted mainly nornicotine. Both species also utilized phase II conjugation reactions to detoxify nicotine, with Cape white-eyes depending more on the mercapturic acid pathway to detoxify nicotine than white-bellied sunbirds. We found that sunbirds and white-eyes, despite having a similar nicotine tolerance, responded differently and used different nicotine-derived metabolites to excrete nicotine.

Effect of gaseous ammonia on nicotine sorption

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webb, A.M.; Singer, B.C.; Nazaroff, W.W.

2002-06-01

Nicotine is a major constituent of environmental tobacco smoke. Sorptive interactions of nicotine with indoor surfaces can substantially alter indoor concentrations. The phenomenon is poorly understood, including whether sorption is fully reversible or partially irreversible. They hypothesize that acid-base chemistry on indoor surfaces might contribute to the apparent irreversibility of nicotine sorption under some circumstances. Specifically, they suggest that nicotine may become protonated on surfaces, markedly reducing its vapor pressure. If so, subsequent exposure of the surface to gaseous ammonia, a common base, could raise the surface pH, causing deprotonation and desorption of nicotine from surfaces. A series of experimentsmore » was conducted to explore the effect of ammonia on nicotine sorption to and reemission from surfaces. The results indicate that, under some conditions, exposure to gaseous ammonia can substantially increase the rate of desorption of previously sorbed nicotine from common indoor surface materials.« less

Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report.

PubMed

Ramôa, Carolina P; Hiler, Marzena M; Spindle, Tory R; Lopez, Alexa A; Karaoghlanian, Nareg; Lipato, Thokozeni; Breland, Alison B; Shihadeh, Alan; Eissenberg, Thomas

2016-04-01

Electronic cigarettes (ECIGs) aerosolise a liquid that usually contains propylene glycol and/or vegetable glycerine, flavourants and the dependence-producing drug, nicotine, in various concentrations. This laboratory study examined the relationship between liquid nicotine concentration and plasma nicotine concentration and puffing behaviour in experienced ECIG users. Sixteen ECIG-experienced participants used a 3.3-Volt ECIG battery attached to a 1.5-Ohm dual-coil 'cartomiser' loaded with 1 mL of a flavoured propylene glycol/vegetable glycerine liquid to complete four sessions, at least 2 days apart, that differed by nicotine concentration (0, 8, 18 or 36 mg/mL). In each session, participants completed two 10-puff ECIG-use bouts (30 s puff interval) separated by 60 min. Venous blood was sampled to determine plasma nicotine concentration. Puff duration, volume and average flow rate were measured. Immediately after bout 1, mean plasma nicotine concentration was 5.5 ng/mL (SD=7.7) for 0 mg/mL liquid, with significantly (p<0.05) higher mean concentrations observed for the 8 (mean=17.8 ng/mL, SD=14.6), 18 (mean=25.9 ng/mL, SD=17.5) and 36 mg/mL (mean=30.2 ng/mL; SD=20.0) concentrations; a similar pattern was observed for bout 2. For bout 1, at 36 mg/mL, the mean post- minus pre-bout difference was 24.1 ng/mL (SD=18.3). Puff topography data were consistent with previous results and revealed few reliable differences across conditions. This study demonstrates a relationship between ECIG liquid nicotine concentration and user plasma nicotine concentration in experienced ECIG users. Nicotine delivery from some ECIGs may exceed that of a combustible cigarette. The rationale for this higher level of nicotine delivery is uncertain. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Extended nicotine self-administration increases sensitivity to nicotine, motivation to seek nicotine and the reinforcing properties of nicotine-paired cues.

PubMed

Clemens, Kelly J; Lay, Belinda P P; Holmes, Nathan M

2017-03-01

An array of pharmacological and environmental factors influence the development and maintenance of tobacco addiction. The nature of these influences likely changes across the course of an extended smoking history, during which time drug seeking can become involuntary and uncontrolled. The present study used an animal model to examine the factors that drive nicotine-seeking behavior after either brief (10 days) or extended (40 days) self-administration training. In Experiment 1, extended training increased rats' sensitivity to nicotine, indicated by a leftward shift in the dose-response curve, and their motivation to work for nicotine, indicated by an increase in the break point achieved under a progressive ratio schedule. In Experiment 2, extended training imbued the nicotine-paired cue with the capacity to maintain responding to the same high level as nicotine itself. However, Experiment 3 showed that the mechanisms involved in responding for nicotine or a nicotine-paired cue are dissociable, as treatment with the partial nicotine receptor agonist, varenicline, suppressed responding for nicotine but potentiated responding for the nicotine-paired cue. Hence, across extended nicotine self-administration, pharmacological and environmental influences over nicotine seeking increase such that nicotine seeking is controlled by multiple sources, and therefore highly resistant to change. © 2015 Society for the Study of Addiction.

Chronic nicotine administration differentially affects neurotransmitter release from rat striatal slices.

PubMed

Yu, Z J; Wecker, L

1994-07-01

The objective of these experiments was to determine whether the chronic administration of nicotine, at a dose regimen that increases the density of nicotine binding sites, alters the nicotine-induced release of [3H]-dopamine ([3H]DA), [3H]norepinephrine ([3H]NE), [3H]-serotonin ([3H]5-HT), or [3H]acetylcholine ([3H]ACh) from rat striatal slices. For these experiments, rats received subcutaneous injections of either saline or nicotine bitartrate [1.76 mg (3.6 mumol)/kg, dissolved in saline] twice daily for 10 days, and neurotransmitter release was measured following preloading of the tissues with [3H]DA, [3H]NE, [3H]5-HT, or [3H]choline. Chronic nicotine administration did not affect the accumulation of tritium by striatal slices, the basal release of radioactivity, or the 25 mM KCl-evoked release of neurotransmitter. Superfusion of striatal slices with 1, 10, and 100 microM nicotine increased [3H]DA release in a concentration-dependent manner, and release from slices from nicotine-injected animals was significantly (p < 0.05) greater than release from saline-injected controls; release from the former increased to 132, 191, and 172% of release from the controls following superfusion with 1, 10, and 100 microM nicotine, respectively. Similarly, [3H]5-HT release increased in a concentration-related manner following superfusion with nicotine, and release from slices from nicotine-injected rats was significantly (p < 0.05) greater than that from controls. [3H]5-HT release from slices from nicotine-injected rats evoked by superfusion with 1 and 10 microM nicotine increased to 453 and 217%, respectively, of release from slices from saline-injected animals. The nicotine-induced release of [3H]NE from striatal slices was also concentration dependent but was unaffected by chronic nicotine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased hepatic nicotine elimination after phenobarbital induction in the conscious rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foth, H.; Walther, U.I.; Kahl, G.F.

1990-09-15

Elimination parameters of (14C)nicotine in conscious rats receiving nicotine (0.3 mg/kg) either intravenously or orally were studied. The oral availability of unchanged nicotine, derived by comparison of the respective areas under the concentration vs time curves (AUC), was 89%, indicating low hepatic extraction ratios of about 10%. Pretreatment of rats with phenobarbital (PB) markedly increased hepatic first-pass extraction of nicotine. The oral availability of unchanged nicotine in plasma dropped to 1.4% of the corresponding values obtained from PB-treated rats receiving nicotine iv. After PB pretreatment, the clearance of iv nicotine was increased approximately twofold over controls, much less than themore » observed more than ninefold increase of hepatic first-pass extraction. It is assumed that extrahepatic metabolism contributed significantly to the rapid removal of nicotine from the plasma. The elimination of cotinine, originating from nicotine administered either po or iv, was significantly increased by PB pretreatment, as determined by the ratio of corresponding AUCs. The pattern of nicotine metabolites in urine also indicated an increase in the rate of cotinine metabolic turnover. The amount of norcotinine in the organic extract of urine paralleled PB microsomal enzyme induction. The ratio between urinary concentrations of the normetabolite and cotinine correlated strongly with the PB-induced state of rat liver. This may be a suitable indicator of PB-inducible hepatic cytochrome P450 isoenzyme(s). Since smoking habits in man are feedback-regulated by nicotine plasma concentrations, a similar increase of nicotine elimination by microsomal enzyme induction in man may be of relevance for tobacco consumption.« less

Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS).

PubMed

Leigh, Noel J; Lawton, Ralph I; Hershberger, Pamela A; Goniewicz, Maciej L

2016-11-01

E-cigarettes or electronic nicotine delivery systems (ENDS) are designed to deliver nicotine-containing aerosol via inhalation. Little is known about the health effects of flavoured ENDS aerosol when inhaled. Aerosol from ENDS was generated using a smoking machine. Various types of ENDS devices or a tank system prefilled with liquids of different flavours, nicotine carrier, variable nicotine concentrations and with modified battery output voltage were tested. A convenience sample of commercial fluids with flavour names of tobacco, piña colada, menthol, coffee and strawberry were used. Flavouring chemicals were identified using gas chromatography/mass spectrometry. H292 human bronchial epithelial cells were directly exposed to 55 puffs of freshly generated ENDS aerosol, tobacco smoke or air (controls) using an air-liquid interface system and the Health Canada intense smoking protocol. The following in vitro toxicological effects were assessed: (1) cell viability, (2) metabolic activity and (3) release of inflammatory mediators (cytokines). Exposure to ENDS aerosol resulted in decreased metabolic activity and cell viability and increased release of interleukin (IL)-1β, IL-6, IL-10, CXCL1, CXCL2 and CXCL10 compared to air controls. Cell viability and metabolic activity were more adversely affected by conventional cigarettes than most tested ENDS products. Product type, battery output voltage and flavours significantly affected toxicity of ENDS aerosol, with a strawberry-flavoured product being the most cytotoxic. Our data suggest that characteristics of ENDS products, including flavours, may induce inhalation toxicity. Therefore, ENDS users should use the products with caution until more comprehensive studies are performed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effect of nicotine and cotinine on human gingival fibroblasts attachment to root surfaces.

PubMed

Esfahrood, Zeinab Rezaei; Zamanian, Amirhosein; Torshabi, Maryam; Abrishami, Maryam

2015-09-01

Different compounds of smoking (e.g., nicotine and cotinine) are risk factors for various diseases such as oral cancer and periodontal diseases. Some studies reported the negative effects of nicotine on cell proliferation and differentiation. The present in vitro study assessed the effects of nicotine and cotinine (long-acting metabolite of nicotine) on the attachment and viability of human gingival fibroblast (HGF) cells to tooth root surfaces. A total of 70 teeth specimens were placed into 48-well culture plates and covered with HGF cell suspension, in complete Dulbecco's modified Eagle's medium culture medium containing 1 nM, 1 μm, 1 mM, and 5 mM of nicotine and cotinine concentrations. Cellular attachment and viability measured using an MTT assay and a scanning electron microscope were used for cell morphological evaluation. After 24 h, low (nanomolar and micromolar) and high concentrations (millimolar) of nicotine and cotinine caused a significant reduction in the initial cell adhesion in comparison with the control group, but no significant difference was observed between the nicotine and the cotinine groups (p<0.05). Dentally attached cells with low concentrations of nicotine and cotinine proliferated 48 h after exposure, the same as the control group. However, dentally attached cells with high concentrations of nicotine and cotinine (especially 5 mM) did not proliferate 24 h after exposure (p<0.05). Low concentrations of nicotine and cotinine caused a reduction in the initial cell adhesion. However, no significant adverse effects on the proliferation of attached cells were seen in the longer period. High concentrations of nicotine and cotinine have adverse effects on the cell adhesion and proliferation of HGF cells.

The Influence of a Mouthpiece-Based Topography Measurement Device on Electronic Cigarette User's Plasma Nicotine Concentration, Heart Rate, and Subjective Effects Under Directed and Ad Libitum Use Conditions.

PubMed

Spindle, Tory R; Hiler, Marzena M; Breland, Alison B; Karaoghlanian, Nareg V; Shihadeh, Alan L; Eissenberg, Thomas

2017-04-01

Electronic cigarettes e-cigarettes aerosolize a liquid solution often containing nicotine. e-cigarette nicotine delivery may be influenced by user puffing behaviors ("puff topography"). E-cigarette puff topography can be recorded using mouthpiece-based computerized systems. The present study sought to examine the extent to which these systems influence e-cigarette nicotine delivery and other e-cigarette associated acute effects under ad libitum use conditions. Plasma nicotine concentration, heart rate, and subjective effects were assessed in 29 experienced e-cigarette users using their preferred e-cigarette battery and liquid (≥12mg/mL nicotine) in two sessions differing only by the presence of a mouthpiece-based device. In both sessions, participants completed a directed e-cigarette use bout (10 puffs, 30-s interpuff interval) and a 90-min ad libitum bout. Puff topography was recorded in the session with the topography mouthpiece. Plasma nicotine, heart rate, and subjective effects, aside from "Did the e-cigarette Taste Good?" were independent of topography measurement (higher mean taste ratings were observed in the no topography condition). Mean (SEM) plasma nicotine concentration following the ad libitum bout was 34.3ng/mL (4.9) in the no topography condition and 35.7ng/mL (4.3) in the topography condition. Longer puff durations, longer interpuff intervals, and larger puff volumes were observed in the ad libitum relative to the directed bout. E-cigarette use significantly increased plasma nicotine concentration and heart rate while suppressing abstinence symptoms. These effects did not differ when a topography mouthpiece was present. Future studies using ad libitum e-cigarette use bouts would facilitate understanding of e-cigarette toxicant yield. No prior study has examined whether mouthpiece-based topography recording devices influence e-cigarette associated nicotine delivery, heart rate, or subjective effects under ad libitum conditions or assessed ad

Cotinine antagonizes the behavioral effects of nicotine exposure in the planarian Girardia tigrina.

PubMed

Bach, Daniel J; Tenaglia, Matthew; Baker, Debra L; Deats, Sean; Montgomery, Erica; Pagán, Oné R

2016-10-06

Nicotine is one of the most addictive drugs abused by humans. Our laboratory and others have demonstrated that nicotine decreases motility and induces seizure-like behavior in planarians (pSLM, which are vigorous writhing and bending of the body) in a concentration-dependent manner. Nicotine also induces withdrawal-like behaviors in these worms. Cotinine is the major nicotine metabolite in humans, although it is not the final product of nicotine metabolism. Cotinine is mostly inactive in vertebrate nervous systems and is currently being explored as a molecule which possess most of nicotine's beneficial effects and few of its undesirable ones. It is not known whether cotinine is a product of nicotine metabolism in planarians. We found that cotinine by itself does not seem to elicit any behavioral effects in planarians up to a concentration of 1mM. We also show that cotinine antagonizes the aforementioned nicotine-induced motility decrease and also decreases the expression of nicotine-induced pSLMs in a concentration-dependent manner. Also cotinine prevents the manifestation of some of the withdrawal-like behaviors induced by nicotine in our experimental organism. Thus, we obtained evidence supporting that cotinine antagonizes nicotine in this planarian species. Possible explanations include competitive binding of both compounds at overlapping binding sites, at different nicotinic receptor subtypes, or maybe allosteric interactions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nicotine and Cotinine Exposure from Electronic Cigarettes: A Population Approach

PubMed Central

de Mendizábal, Nieves Vélez; Jones, David R.; Jahn, Andy; Bies, Robert R.; Brown, Joshua W.

2015-01-01

Background and Objectives Electronic cigarettes (e-cigarettes) are a recent technology that has gained rapid acceptance. Still, little is known about them in terms of safety and effectiveness. A basic question is how effectively they deliver nicotine, however the literature is surprisingly unclear on this point. Here, a population pharmacokinetic (PK) model was developed for nicotine and its major metabolite cotinine with the aim to provide a reliable framework for the simulation of nicotine and cotinine concentrations over time, based solely on inhalation airflow recordings and individual covariates (i.e. weight and breath carbon monoxide CO levels). Methods This study included 10 adults self-identified as heavy smokers (at least one pack per day). Plasma nicotine and cotinine concentrations were measured at regular 10-minute intervals for 90 minutes while human subjects inhaled nicotine vapor from a modified e-cigarette. Airflow measurements were recorded every 200 milliseconds throughout the session. A population PK model for nicotine and cotinine was developed based on previously published PK parameters and the airflow recordings. All the analyses were performed with the nonlinear mixed-effect modelling software NONMEM 7.2. Results The results show that e-cigarettes deliver nicotine effectively, although the pharmacokinetic profiles are lower than those achieved with regular cigarettes. Our PK model effectively predicts plasma nicotine and cotinine concentrations from the inhalation volume, and initial breath CO. Conclusion E-cigarettes are effective at delivering nicotine. This new PK model of e-cigarette usage might be used for pharmacodynamic analysis where the PK profiles are not available. PMID:25503588

Prenatal nicotine exposure increases hyperventilation in α4-knock-out mice during mild asphyxia.

PubMed

Avraam, Joanne; Cohen, Gary; Drago, John; Frappell, Peter B

2015-03-01

Prenatal nicotine exposure alters breathing and ventilatory responses to stress through stimulation of nicotine acetylcholine receptors (nAChRs). We tested the hypothesis that α4-containing nAChRs are involved in mediating the effects of prenatal nicotine exposure on ventilatory and metabolic responses to intermittent mild asphyxia (MA). Using open-flow plethysmography, we measured ventilation (V̇(E)) and rate of O2 consumption ( V̇(O2)) of wild-type (WT) and α4-knock-out (KO) mice, at postnatal (P) days 1-2 and 7-8, with and without prenatal nicotine exposure (6 mg kg(-1) day(-1) beginning on embryonic day 14). Mice were exposed to seven 2 min cycles of mild asphyxia (10% O2 and 5% CO2), each interspersed with 2 min of air. Compared to WT, α4 KO mice had increased air V̇(E) and V̇(O2) at P7-8, but not P1-2. Irrespective of age, genotype had no effect on the hyperventilatory response (increase in V̇(E)/V̇(O2)) to MA. At P1-2, nicotine suppressed air V̇(E) and V̇(O2) in both genotypes but did not affect the hyperventilatory response to MA. At P7-8 nicotine suppressed air V̇(E) and V̇(O2) of only α4 KO's but also significantly enhanced V̇(E) during MA (nearly double that of WT; p<0.001). This study has revealed complex effects of α4 nAChR deficiency and prenatal nicotine exposure on ventilatory and metabolic interactions and responses to stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Studying the interactive effects of menthol and nicotine among youth: An examination using e-cigarettes.

PubMed

Krishnan-Sarin, Suchitra; Green, Barry G; Kong, Grace; Cavallo, Dana A; Jatlow, Peter; Gueorguieva, Ralitza; Buta, Eugenia; O'Malley, Stephanie S

2017-11-01

Tobacco products containing menthol are widely used by youth. We used e-cigarettes to conduct an experimental evaluation of the independent and interactive effects of menthol and nicotine among youth. Pilot chemosensory experiments with fourteen e-cigarette users identified low (barely perceptible, 0.5%) and high (similar to commercial e-liquid, 3.5%) menthol concentrations. Sixty e-cigarette users were randomized to a nicotine concentration (0mg/ml, 6mg/ml, 12mg/ml) and participated in 3 laboratory sessions. During each session, they received their assigned nicotine concentration, along with one of three menthol concentrations in random counterbalanced order across sessions (0, 0.5%, 3.5%), and participated in three fixed-dose, and an ad-lib, puffing period. Urinary menthol glucuronide and salivary nicotine levels validated menthol and nicotine exposure. We examined changes in e-cigarette liking/wanting and taste, coolness, stimulant effects, nicotine withdrawal and ad-lib use. Overall, the high concentration of menthol (3.5%) significantly increased e-cigarette liking/wanting relative to no menthol (p<0.001); there was marginal evidence of nicotine* menthol interactions (p=0.06), with an increase in liking/wanting when 3.5% menthol was combined with 12mg/ml nicotine, but not 6mg/ml nicotine. Importantly, both 0.5% and 3.5% menthol concentrations significantly improved taste and increased coolness. We did not observe nicotine or menthol-related changes in stimulant effects, nicotine withdrawal symptoms or ad-lib use. Menthol, even at very low doses, alters the appeal of e-cigarettes among youth. Further, menthol enhances positive rewarding effects of high nicotine-containing e-cigarettes among youth. Copyright © 2017 Elsevier B.V. All rights reserved.

Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.

PubMed

Hansson, Anna; Rasmussen, Thomas; Kraiczi, Holger

2017-04-01

Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed. In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables. In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL). Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT. Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine

Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians.

PubMed

Pagán, Oné R; Montgomery, Erica; Deats, Sean; Bach, Daniel; Baker, Debra

2015-10-01

Planarians are rapidly developing into very useful research subjects in pharmacology and neuroscience research. Here we report that curare, a cholinergic nicotinic receptor antagonist, alleviates the nicotine-induced planarian seizure-like movements (pSLM) by up to 50 % at equimolar concentrations of nicotine and curare (1 mM), while curare alone does not induce significant pSLMs. The simplest interpretation of our data is that there are nicotine induced behaviors insensitive to curare in our experimental organism. To the best of our knowledge, this is the first report on curare-insensitive, nicotine-induced effects in any organism.

Nicotine-induced stimulation of steroidogenesis in adrenocortical cells of the cat.

PubMed Central

Rubin, R P; Warner, W

1975-01-01

1. The effect of nicotine on steroid production and release from trypsin-dispersed cat adrenocortical cells was investigated. 2. Nicotine, like adrenocorticotrophin (ACTH), elicited a dose-dependent increase in steroidogenesis, which depended upon the presence of calcium in the medium. 3. Augmented steroid production evoked by submaximal concentrations of ACTH monobutyryl cyclic adenosine 3',5'-monophosphate (AMP), or prostaglandin E2 was further enhanced by steroidogenic concentrations of nicotine. 4. These results are discussed in relation to the possible mode of action of nicotine on cortical cells and to the potential consequences of smoking during stress. PMID:165845

A pilot study on nicotine residues in houses of electronic cigarette users, tobacco smokers, and non-users of nicotine-containing products.

PubMed

Bush, Derek; Goniewicz, Maciej L

2015-06-01

Nicotine deposited on the surfaces has been shown to react with airborne chemicals leading to formation of carcinogens and contributing to thirdhand exposure. While prior studies revealed nicotine residues in tobacco smokers' homes, none have examined the nicotine residue in electronic cigarette (e-cigarette) users' homes. We measured nicotine on the surfaces in households of 8 e-cigarette users, 6 cigarette smokers, and 8 non-users of nicotine-containing products in Western New York, USA. Three surface wipe samples were taken from the floor, wall and window. Nicotine was extracted from the wipes and analyzed using gas chromatography. Half of the e-cigarette users' homes had detectable levels of nicotine on surfaces whereas nicotine was found in all of the tobacco cigarette smokers' homes. Trace amounts of nicotine were also detected in half of the homes of non-users of nicotine-containing products. Nicotine levels in e-cigarette users homes was significantly lower than that found in cigarette smokers homes (average concentration 7.7±17.2 vs. 1303±2676 μg/m2; p<0.05). There was no significant difference in the amount of nicotine in homes of e-cigarette users and non-users (p>0.05). Nicotine is a common contaminant found on indoor surfaces. Using e-cigarettes indoors leads to significantly less thirdhand exposure to nicotine compared to smoking tobacco cigarettes. Copyright © 2015 Elsevier B.V. All rights reserved.

Complex osteoclastogenic inductive effects of nicotine over hydroxyapatite.

PubMed

Costa-Rodrigues, Joao; Rocha, Isabel; Fernandes, Maria H

2018-02-01

Cigarette smoke is associated to pathological weakening of bone tissue, being considered an important playmaker in conditions such as osteoporosis and periodontal bone loss. In addition, it is also associated with an increased risk of failure in bone regeneration strategies. The present work aimed to characterize the effects of nicotine on human osteoclastogenesis over a hydroxyapatite substrate. Osteoclast precursors were maintained in the absence or presence of the osteoclastogenesis enhancers M-CSF and RANKL, and were further treated with nicotine levels representative of the concentrations observed in the plasma and saliva of smokers. It was observed that nicotine at low concentrations elicit an increase in osteoclast differentiation, but only in the presence of M-CSF and RANKL it was also able to significantly increase the resorbing ability of osteoclasts. A slight downregulation of NFkB pathway and an increase in the production of TNF-α and, particularly PGE2, were involved in the observed effects of nicotine. At high concentrations, nicotine revealed cytotoxic effects, causing a decrease in cell density. In conclusion, nicotine at levels found in the plasma of the smokers, has the ability to act directly on osteoclast precursors, inducing its osteoclastogenic differentiation. The stimulatory behavior appears to be dependent on the stage of osteoclastic differentiation of the precursor cells, which means, in the absence of M-CSF and RANKL, it only favors the initial stages of osteoclast differentiation, while in the presence of the growth factors, a significant increase in their resorbing ability is also achieved. © 2017 Wiley Periodicals, Inc.

Nicotine delivery, retention, and pharmacokinetics from various electronic cigarettes

PubMed Central

St. Helen, Gideon; Havel, Christopher; Dempsey, Delia; Jacob, Peyton; Benowitz, Neal L.

2015-01-01

Aims To measure the systemic retention of nicotine, propylene glycol (PG), and vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics. Design E-cigarette users recruited over the Internet participated in a 1-day research ward study. Subjects took 15 puffs from their usual brand of e-cigarette. Exhaled breath was trapped in gas-washing bottles and blood was sampled before and several time after use. Setting San Francisco, California, USA. Participants Thirteen healthy, experienced adult e-cigarette users (6 females and 7 males). Measurements Plasma nicotine was analyzed by GC-MS/MS, and nicotine, VG, and PG in e-liquids and gas traps were analyzed by LC-MS/MS. Heart rate changes and subjective effects were assessed. Findings E-cigarettes delivered an average of 1.3 (0.9–1.8) mg (mean and 95% CI) of nicotine and 94% of the inhaled dose, 1.2 (0.8–1.7), was systemically retained. Average maximum plasma nicotine concentration (Cmax) was 8.4 (5.4–11.5) ng/mL and time of maximal concentration (Tmax) was 2 to 5 minutes; one participant had Tmax of 30 minutes. 89% and 92% of VG and PG, respectively, was systemically retained. Heart rate increased by an average of 8.0 bpm after 5 minutes. Withdrawal and urge to smoke decreased and the e-cigarettes were described as satisfying. Conclusions E-cigarettes can deliver levels of nicotine that are comparable to or higher than typical tobacco cigarettes, with similar systemic retention. Although the average maximum plasma nicotine concentration in experienced e-cigarettes users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential. PMID:26430813

Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes.

PubMed

St Helen, Gideon; Havel, Christopher; Dempsey, Delia A; Jacob, Peyton; Benowitz, Neal L

2016-03-01

To measure the systemic retention of nicotine, propylene glycol (PG) and vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics. E-cigarette users recruited over the internet participated in a 1-day research ward study. Subjects took 15 puffs from their usual brand of e-cigarette. Exhaled breath was trapped in gas-washing bottles and blood was sampled before and several times after use. San Francisco, California, USA. Thirteen healthy, experienced adult e-cigarette users (six females and seven males). Plasma nicotine was analyzed by gas chromatography-mass spectrometry (GC-MS/MS) and nicotine, VG and PG in e-liquids and gas traps were analyzed by LC-MS/MS. Heart rate changes and subjective effects were assessed. E-cigarettes delivered an average of 1.33 (0.87-1.79) mg [mean and 95% confidence interval (CI)] of nicotine, and 93.8% of the inhaled dose, 1.22 (0.80-1.66) was systemically retained. Average maximum plasma nicotine concentration (Cmax ) was 8.4 (5.4-11.5) ng/ml and time of maximal concentration (Tmax ) was 2-5 minutes. One participant had Tmax of 30 minutes. 84.4% and 91.7% of VG and PG, respectively, was systemically retained. Heart rate increased by an average of 8.0 beats per minute after 5 minutes. Withdrawal and urge to smoke decreased and the e-cigarettes were described as satisfying. E-cigarettes can deliver levels of nicotine that are comparable to or higher than typical tobacco cigarettes, with similar systemic retention. Although the average maximum plasma nicotine concentration in experienced e-cigarette users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential. © 2015 Society for the Study of Addiction.

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.

PubMed

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

A review of the impacts of tobacco heating system on indoor air quality versus conventional pollution sources.

PubMed

Kaunelienė, Violeta; Meišutovič-Akhtarieva, Marija; Martuzevičius, Dainius

2018-05-08

With the introduction of novel and potentially less polluting nicotine containing products to the market, the impacts of their usage to indoor air quality as opposed to conventional pollution sources must be reviewed and considered. This review study aimed to comparatively analyse changes in indoor air quality as the consequence of tobacco heating system (THS) generated pollution against general indoor air quality in various micro-environments, especially with combustion-based pollution sources present. Indoor concentrations of formaldehyde, acetaldehyde, benzene, toluene, nicotine and PM 2.5 were reviewed and compared; concentrations of other harmful and potentially harmful substances (HPHCs) were discussed. Generally, the usage of THS has been associated with lower or comparable indoor air pollutant concentrations compared against other conventional indoor sources or environments, in most cases distinguishable above background, thus potentially being associated with health effects at prolonged exposures as any other artificial air pollution source. In the controlled environment the use of THS (as well as an electronic cigarette) resulted in the lowest concentrations of formaldehyde, benzene, toluene, PM 2.5, among majority researched pollution sources (conventional cigarettes, waterpipe, incense, mosquito coils). The exposure to significantly higher pollution levels of benzene, toluene, and formaldehyde occurred in public environments, especially transport micro-environments. Such low levels of conventionally-assessed indoor pollutants resulting from the use of new nicotine containing products raise challenges for epidemiological studies of second-hand exposure to THS aerosol in real-life environments. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Use of Nicotine in Electronic Nicotine and Non-Nicotine Delivery Systems by US Adults, 2015.

PubMed

Weaver, Scott R; Kemp, Catherine B; Heath, J Wesley; Pechacek, Terry F; Eriksen, Michael P

Nicotine in electronic nicotine and non-nicotine delivery systems (ENDS/ENNDS) may present a risk of harm to those with cardiovascular disease and the fetuses of pregnant women. We assessed the extent to which adult users of ENDS/ENNDS used these products with nicotine. We obtained data for this study from a national probability survey of 6051 US adults that was conducted in August and September 2015. Of 399 adult ENDS/ENNDS users who were current smokers, 337 (80.7%) used ENDS/ENNDS containing nicotine, whereas only 29 of 71 (36.9%) ENDS/ENNDS users who were never smokers used ENDS/ENNDS containing nicotine. Assessments of the population health impact of ENDS/ENNDS use among never smokers should take into account the extent to which use involves nicotine.

Nicotine Delivery and Vaping Behavior During ad Libitum E-cigarette Access

PubMed Central

St.Helen, Gideon; Ross, Kathryn C.; Dempsey, Delia A.; Havel, Christopher M.; Jacob, Peyton; Benowitz, Neal L.

2017-01-01

Objective To characterize vaping behavior and nicotine intake during ad libitum e-cigarette access. Methods Thirteen adult e-cigarette users had 90 minutes of videotaped ad libitum access to their usual e-cigarette. Plasma nicotine was measured before and every 15 minutes after the first puff; subjective effects were measured before and after the session. Results Average puff duration and interpuff interval were 3.5±1.4 seconds (±SD) and 118±141 seconds, respectively. 12% of puffs were unclustered puffs while 43%, 28%, and 17% were clustered in groups of 2–5, 6–10, and >10 puffs, respectively. On average, 4.0±3.3 mg of nicotine was inhaled; the maximum plasma nicotine concentration (Cmax) was 12.8±8.5 ng/mL. Among the 8 tank users, number of puffs was positively correlated with amount of nicotine inhaled, Cmax, and area under the plasma nicotine concentration-time curve (AUC0→90min) while interpuff interval was negatively correlated with Cmax and AUC0→90. Conclusion Vaping patterns differ from cigarette smoking. Plasma nicotine levels were consistent with intermittent dosing of nicotine from e-cigarettes compared to the more bolus dosing from cigarettes. Differences in delivery patterns and peak levels of nicotine achieved could influence the addictiveness of e-cigarettes compared to conventional cigarettes. PMID:28393086

Nicotine Delivery and Vaping Behavior During ad Libitum E-cigarette Access.

PubMed

St Helen, Gideon; Ross, Kathryn C; Dempsey, Delia A; Havel, Christopher M; Jacob, Peyton; Benowitz, Neal L

2016-10-01

To characterize vaping behavior and nicotine intake during ad libitum e-cigarette access. Thirteen adult e-cigarette users had 90 minutes of videotaped ad libitum access to their usual e-cigarette. Plasma nicotine was measured before and every 15 minutes after the first puff; subjective effects were measured before and after the session. Average puff duration and interpuff interval were 3.5±1.4 seconds (±SD) and 118±141 seconds, respectively. 12% of puffs were unclustered puffs while 43%, 28%, and 17% were clustered in groups of 2-5, 6-10, and >10 puffs, respectively. On average, 4.0±3.3 mg of nicotine was inhaled; the maximum plasma nicotine concentration (C max ) was 12.8±8.5 ng/mL. Among the 8 tank users, number of puffs was positively correlated with amount of nicotine inhaled, C max , and area under the plasma nicotine concentration-time curve (AUC 0 → 90min ) while interpuff interval was negatively correlated with C max and AUC 0 → 90 . Vaping patterns differ from cigarette smoking. Plasma nicotine levels were consistent with intermittent dosing of nicotine from e-cigarettes compared to the more bolus dosing from cigarettes. Differences in delivery patterns and peak levels of nicotine achieved could influence the addictiveness of e-cigarettes compared to conventional cigarettes.

Nicotine and ethanol cooperate to enhance ventral tegmental area AMPA receptor function via α6-containing nicotinic receptors.

PubMed

Engle, Staci E; McIntosh, J Michael; Drenan, Ryan M

2015-04-01

Nicotine + ethanol co-exposure results in additive and/or synergistic effects in the ventral tegmental area (VTA) to nucleus accumbens (NAc) dopamine (DA) pathway, but the mechanisms supporting this are unclear. We tested the hypothesis that nAChRs containing α6 subunits (α6* nAChRs) are involved in the response to nicotine + ethanol co-exposure. Exposing VTA slices from C57BL/6 WT animals to drinking-relevant concentrations of ethanol causes a marked enhancement of α-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA) receptor (AMPAR) function in VTA neurons. This effect was sensitive to α-conotoxin MII (an α6β2* nAChR antagonist), suggesting that α6* nAChR function is required. In mice expressing hypersensitive α6* nAChRs (α6L9S mice), we found that lower concentrations (relative to C57BL/6 WT) of ethanol were sufficient to enhance AMPAR function in VTA neurons. Exposure of live C57BL/6 WT mice to ethanol also produced AMPAR functional enhancement in VTA neurons, and studies in α6L9S mice strongly suggest a role for α6* nAChRs in this response. We then asked whether nicotine and ethanol cooperate to enhance VTA AMPAR function. We identified low concentrations of nicotine and ethanol that were capable of strongly enhancing VTA AMPAR function when co-applied to slices, but that did not enhance AMPAR function when applied alone. This effect was sensitive to both varenicline (an α4β2* and α6β2* nAChR partial agonist) and α-conotoxin MII. Finally, nicotine + ethanol co-exposure also enhanced AMPAR function in VTA neurons from α6L9S mice. Together, these data identify α6* nAChRs as important players in the response to nicotine + ethanol co-exposure in VTA neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

Skin contamination as pathway for nicotine intoxication in vapers.

PubMed

Maina, Giovanni; Castagnoli, Carlotta; Ghione, Giordana; Passini, Valter; Adami, Gianpiero; Larese Filon, Francesca; Crosera, Matteo

2017-06-01

Growing warnings on health effects related to electronic cigarettes have met inconclusive findings at present. This study analyzed the in vitro percutaneous absorption of nicotine resulting by skin contamination with two e-liquids (refill 1 and 2) containing nicotine at 1.8%. Donor chambers of 6 Franz cells for each refill liquid were filled with 1mL of nicotine e-liquid for 24h; at selected intervals, 1.5mL of the receptor solutions were collected for nicotine concentration analysis by mean gas chromatography-mass spectrometry (LOD: 0.01μg/mL). The experiment was repeated removing the nicotine donor solution after 10min from the application and rinsing the skin surface three times with 3.0mL of milliQ water. A total of 12 cells with 24h exposure and 12 cells washed were studied. The mean concentration of nicotine in the receiving phase at the end of the experiment was 54.9±29.5 and 30.2±18.4μg/cm 2 for refill 1 and 2 respectively and significantly lower in washed cells (4.7±2.4 and 3.5±1.3μg/cm 2 ). The skin absorption of nicotine can lead to minor health illness in vapers, while caution must be paid to dermal contamination by e liquids in children. The skin cleaning significantly reduced the transdermal absorption kinetic and intradermal deposition of nicotine. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

PubMed

Elhassan, Sagi; Bagdas, Deniz; Damaj, M Imad

2017-06-01

Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

α-Conotoxin MII-Sensitive Nicotinic Acetylcholine Receptors in the Nucleus Accumbens Shell Regulate Progressive Ratio Responding Maintained by Nicotine

PubMed Central

Brunzell, Darlene H; Boschen, Karen E; Hendrick, Elizabeth S; Beardsley, Patrick M; McIntosh, J Michael

2010-01-01

β2 subunit containing nicotinic acetylcholine receptors (β2*nAChRs; asterisk (*) denotes assembly with other subunits) are critical for nicotine self-administration and nicotine-associated dopamine (DA) release that supports nicotine reinforcement. The α6 subunit assembles with β2 on DA neurons where α6β2*nAChRs regulate nicotine-stimulated DA release at neuron terminals. Using local infusion of α-conotoxin MII (α-CTX MII), an antagonist with selectivity for α6β2*nAChRs, the purpose of these experiments was to determine if α6β2*nAChRs in the nucleus accumbens (NAc) shell are required for motivation to self-administer nicotine. Long-Evans rats lever-pressed for 0.03 mg/kg, i.v., nicotine accompanied by light+tone cues (NIC) or for light+tone cues unaccompanied by nicotine (CUEonly). Following extensive training, animals were tested under a progressive ratio (PR) schedule that required an increasing number of lever presses for each nicotine infusion and/or cue delivery. Immediately before each PR session, rats received microinfusions of α-CTX MII (0, 1, 5, or 10 pmol per side) into the NAc shell or the overlying anterior cingulate cortex. α-CTX MII dose dependently decreased break points and number of infusions earned by NIC rats following infusion into the NAc shell but not the anterior cingulate cortex. Concentrations of α-CTX MII that were capable of attenuating nicotine self-administration did not disrupt locomotor activity. There was no effect of infusion on lever pressing in CUEonly animals and NAc infusion α-CTX MII did not affect locomotor activity in an open field. These data suggest that α6β2*nAChRs in the NAc shell regulate motivational aspects of nicotine reinforcement but not nicotine-associated locomotor activation. PMID:19890263

Variation in Nicotine Consumption in Inbred Mice Is Not Linked to Orosensory Ability

PubMed Central

Glatt, A. Rebecca; Denton, Kelley

2009-01-01

Genetic studies of nicotine addiction in mice have utilized the oral self-administration model. However, it is unclear if strain differences in nicotine consumption are influenced by variation in bitter taste sensitivity. We measured both nicotine consumption and nicotine brief-access licking behavior in several commonly used inbred strains of mice that were previously shown to differ in nicotine consumption. A/J (A), C57BL/6J (B6), and DBA/2J (D2) mice were given a 2-bottle choice test with a single concentration of nicotine (75 μg/ml; nicotine vs. water). Mice of these strains were also tested with a range of nicotine concentrations (5–400 μg/ml) using a brief-access test, which measures orosensory response and minimizes postingestive effects. Although B6 mice consumed more 75-μg/ml nicotine than A or D2 mice in the 2-bottle test, these strains did not differ in level of aversion to nicotine when tested with the brief-access procedure. Strain differences in orosensory response to nicotine were not found; yet, differences emerged during the 2-bottle tests. This study provides evidence that variation in intake level of nicotine is likely not due to differences in taste or trigeminal sensitivity but likely due to postingestive factors. PMID:18775876

Orexin and leptin are associated with nicotine craving: a link between smoking, appetite and reward.

PubMed

von der Goltz, Christoph; Koopmann, Anne; Dinter, Christina; Richter, Anne; Rockenbach, Christine; Grosshans, Martin; Nakovics, Helmut; Wiedemann, Klaus; Mann, Karl; Winterer, Georg; Kiefer, Falk

2010-05-01

Preclinical data suggest modulating effects of both orexin/hypocretin and leptin on dopaminergic transmission in mesolimbic reward pathways. This indicates a possible role of both peptides in reward function and motivation, and thus in addictive diseases. The aim of this study was to examine the possible association between orexin and leptin, and nicotine craving in smokers in a clinical case-control study under standardized conditions. We compared orexin and leptin, ACTH and cortisol plasma concentrations (RIA) between tobacco smokers (n=60) during early nicotine withdrawal and healthy controls (n=64). Motivational aspects of nicotine craving were additionally assessed in the smoking participants using the Questionnaire of Smoking Urges (QSU). As main results we detected a significant negative correlation between orexin plasma concentration and nicotine craving (r=-0.28; p<.05), and a positive association between craving and leptin plasma concentration (r=0.29; p<.05). Our results show an association between craving for nicotine and plasma concentrations of orexin and leptin suggesting that both peptides interfere with the dopaminergic transmission during nicotine withdrawal in a bidirectional manner and, thus, modulate craving for nicotine. Copyright 2009 Elsevier Ltd. All rights reserved.

Direct block of inward rectifier potassium channels by nicotine.

PubMed

Wang, H; Yang, B; Zhang, L; Xu, D; Wang, Z

2000-04-01

Nicotine has been shown to depolarize membrane potential and to lengthen action potential duration in isolated cardiac preparations. To investigate whether this is a consequence of direct interaction of nicotine with inward rectifier K(+) channels which are a key determinant of membrane potentials, we assessed the effects of nicotine on two cloned human inward rectifier K(+) channels, Kir2.1 and Kir2.2, expressed in Xenopus oocytes and the native inward rectifier K(+) current I(K1) in canine ventricular myocytes. Nicotine suppressed Kir2.1-expressed currents at varying potentials negative to -20 mV, with more pronounced effects on the outward current between -70 and -20 mV relative to the inward current at hyperpolarized potentials (below -70 mV). The inhibition was concentration dependent. For the outward currents recorded at -50 mV, the IC50 was 165 +/- 18 microM. Similar effects of nicotine were observed for Kir2.2. A more potent effect was seen with I(K1) in canine myocytes. Significant blockade ( approximately 60%) was found at a concentration as low as 0.5 microM and the IC50 was 4.0 +/- 0.4 microM. The effects in both oocytes and myocytes were partially reversible upon washout of nicotine. Antagonists of nicotinic receptors (mecamylamine, 100 microM), muscarinic receptors (atropine, 1 microM), and beta-adrenergic receptors (propranolol, 1 microM) all failed to restore the depressed currents, suggesting that nicotine acted directly on Kir channels, independent of catecholamine release. This property of nicotine may explain its membrane-depolarizing and action potential duration-prolonging effects in cardiac cells and may contribute in part to its ability to promote propensity for cardiac arrhythmias. Copyright 2000 Academic Press.

Nicotine depresses the functions of multiple cardiac potassium channels.

PubMed

Wang, H; Shi, H; Wang, Z

1999-01-01

Nicotine is the main constituent of tobacco smoke responsible for the elevated risk of the cardiovascular disease and sudden coronary death associated with smoking, presumably by provoking cardiac arrhythmias. The cellular mechanisms may be related to the ability of nicotine to prolong action potentials and to depolarize membrane potential. However, the underlying ionic mechanisms remained unknown. We showed here that nicotine blocked multiple types of K+ currents, including the native currents in canine ventricular myocytes and the cloned channels expressed in Xenopus oocytes: A-type K+ currents (I(to)/Kv4.3), delayed rectifier K+ currents (I(Kr)/HERG) and inward rectifier K+ currents (I(K1)/Kir2.1). Most noticeably, nicotine at a concentration as low as of 10 nM significantly suppressed I(to) and Kv4.3 by approximately 20%. The effects of nicotine were independent of nicotinic receptor simulation or catecholamine release. Our results indicate that nicotine is a non-specific blocker of K+ channels and the inhibitory effects are the consequence of direct interactions between nicotine molecules and the channel proteins. Our study provided for the first time the evidence for the direct inhibition of cardiac K+ channels by nicotine and established a novel aspect of nicotine pharmacology.

Nicotine can modulate the effects of the mesenchymal stem cells on neutrophils.

PubMed

Pourtayeb, Samira; Abtahi Froushani, Seyyed Meysam

2017-03-01

It has been revealed that mesenchymal stem cells (MSCs) express some of the nicotinic receptor subunits. Moreover, the crosstalk between MSCs and neutrophils is not far-fetched. Therefore, the aim of the present study is to determine the role of nicotine on the effects of MSCs on neutrophils. After the isolation of mesenchymal stem cells from the bone marrow of rats, these cells were pulsed with different concentrations of nicotine (0, 0.1, 0.5, and 1μM) for different periods (24, 48, and 72h). Then, the neutrophils were co-cultured with MSCs for 4h and the functions of neutrophils were evaluated. The obtained findings showed that MSCs pulsed with nicotine significantly enhanced the viability and the phagocytic activity of co-cultured neutrophils and simultaneously, decreased the production of reactive oxygen substances (ROS), induced by f-MLP in neutrophils, more profound than MSCs without treatment. Moreover, MSCs, pulsed with nicotine at low to moderate concentrations, preserved the respiratory burst, triggered by opsonized yeast in neutrophils. Nevertheless, a high concentration of nicotine can interfere with the latter aspect of the crosstalk between MSCs and neutrophils. The obtained data can offer a new insight into the potential mechanisms, underlying the immunomodulatory effects of nicotine. Copyright © 2016 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro.

PubMed

Ying, Xiaozhou; Zhang, Wei; Cheng, Shaowen; Nie, Pengfei; Cheng, Xiaojie; Shen, Yue; Wang, Wei; Xue, Enxing; Chen, Qingyu; Kou, Dongquan; Peng, Lei; Zhang, Yu; Lu, Chuanzhu

2012-11-01

Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. However, there is no relevant research concerning on chondrogenic differentiation potential of bone marrow stromal stem cells (BMSCs) treated with nicotine in vitro. The aims of the study were to examine the effects of nicotine (0, 10(-7), 10(-6) and 10(-5) M) on the proliferation and chondrogenic differentiation of BMSCs from three healthy donors in vitro. BMSCs proliferation was analyzed by CCK8 assay and real-time polymerase chain reaction was used to assay the expression of type II collagen, aggrecan, type I collagen and type X collagen. The proteoglycan content was stained by Alcian blue, and the sulfated glycosaminoglycan (sGAG) content of BMSCs was quantified spectrofluorometrically using dimethylmethylene blue. The cell viability was not significantly impaired until up to a concentration of 10(-5) M nicotine. Nicotine promoted the proliferation and enhanced the expression of type II collagen at the level up to 10(-6) M (P < 0.05). The expression of aggrecan was reduced at the concentration of 10(-5) M nicotine at day 14 (P < 0.05), and there was no significant difference in aggrecan gene expression at 10(-7) and 10(-6) M nicotine levels compared to control group (n.s.). Also the fibroblastic and hypertrophic gene expressions were down-regulated in the chondrogenic medium with 10(-7)-10(-5) M nicotine (P < 0.05). It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing chondrogenic differentiation capacity of BMSCs in cell-based cartilage tissue engineering. Also these results indicate that nicotine maybe a potentially useful drug for the treatment of Osteoarthritis.

Reinstatement of nicotine self-administration in rats by presentation of nicotine-paired stimuli, but not nicotine priming.

PubMed

LeSage, Mark G; Burroughs, Danielle; Dufek, Matthew; Keyler, Daniel E; Pentel, Paul R

2004-11-01

The objective of the present study was to determine the relative efficacy of nicotine priming and nicotine-paired stimuli in reinstating extinguished NSA in rats. The relative efficacy of different stimulus conditions in reinstating NSA was also determined. Rats were trained to self-administer nicotine (0.03 mg/kg/inf) under an FR 5 schedule. Onset of a light above the active lever was correlated with nicotine availability, while offset of the light was paired with each nicotine infusion. In Experiment 1, saline extinction was arranged in the presence of these light stimuli. After extinction criteria were met, the effects of priming doses of nicotine (0.01, 0.03. and 0.06 mg/kg/inf, i.v.) on active lever pressing were determined. In Experiment 2, extinction of NSA was arranged in the absence of the light stimuli. After extinction criteria were met, reinstatement sessions were arranged involving either (1) a priming infusion of nicotine (0.03 mg/kg), (2) presentation of the same light stimuli as during NSA training, (3) constant illumination of the cue light, or (4) a combination of a nicotine priming infusion with one of the stimulus-light conditions. In Experiment 1, nicotine generally failed to reinstate NSA at any priming dose. In Experiment 2, both stimulus conditions reinstated NSA, with the stimulus condition identical to training producing a greater effect. Nicotine priming alone failed to significantly reinstate NSA. Nicotine priming combined with either stimulus condition was no more effective than each stimulus condition alone in reinstating NSA. These findings suggest that nicotine-paired cues are more effective than nicotine alone in reinstating extinguished NSA and are consistent with other studies showing that nicotine-paired stimuli play an important role in the reacquisition of NSA.

Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiao, Dan; Seidler, Frederic J.; Slotkin, Theodore A.

Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E. Initiating differentiationmore » with nerve growth factor, which enhances nicotinic acetylcholine receptor expression, increased the TBARS response to nicotine but not chlorpyrifos, suggesting that the two agents act by different originating mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine protected the cells from oxidative damage evoked by chlorpyrifos and similarly blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with nicotine elicited increases in TBARS in multiple brain regions when given in doses that simulate plasma nicotine concentrations found in smokers or at one-tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit oxidative damage to developing neural cells both in vitro and in vivo, a mechanism that explains some of the neurodevelopmental endpoints that are common to the two agents. The balance between neuroprotectant and neurotoxicant actions of nicotine may be particularly important in situations where exposure to tobacco smoke is combined with other prooxidant insults.« less

Nasal nicotine solution: a potential aid to giving up smoking?

PubMed Central

Russell, M A; Jarvis, M J; Feyerabend, C; Fernö, O

1983-01-01

A nasal solution was developed containing 2 mg nicotine for use as a kind of liquid snuff. Its absorption was studied in three subjects. An average peak of plasma nicotine concentrations of 86.9 nmol/l (14.1 ng/ml) was reached seven and a half minutes after taking the solution. This compared with an average peak of 158.4 nmol/l (25.7 ng/ml) one and a half minutes after completing (but seven and a half minutes after starting) a middle tar cigarette (1.4 mg nicotine) and an average peak of 52.4 nmol/l (8.5 ng/ml) after chewing nicotine gum (2 mg nicotine) for 30 minutes. The more rapid and efficient absorption of nicotine from the nasal nicotine solution than from nicotine chewing gum suggests that it might prove a useful aid to giving up smoking. Nasal nicotine solution might be particularly useful in smokers for whom the gum is less suitable on account of dentures or peptic ulcers or who experience nausea and dyspeptic symptoms from the gum. PMID:6402202

Nicotine Dependence, Nicotine Metabolism, and the Extent of Compensation in Response to Reduced Nicotine Content Cigarettes.

PubMed

Bandiera, Frank C; Ross, Kathryn C; Taghavi, Seyedehtaraneh; Delucchi, Kevin; Tyndale, Rachel F; Benowitz, Neal L

2015-09-01

The Food and Drug Administration has the authority to regulate tobacco product constituents, including nicotine, to promote public health. Reducing the nicotine content in cigarettes may lead to lower levels of addiction. Smokers however may compensate by smoking more cigarettes and/or smoking more intensely. The objective of this study was to test whether individual differences in the level of nicotine dependence (as measured by the Fagerstrom Test of Cigarette Dependence [FTCD]) and/or the rate of nicotine metabolism influence smoking behavior and exposure to tobacco toxicants when smokers are switched to reduced nicotine content cigarettes (RNC). Data from 51 participants from a previously published clinical trial of RNC were analyzed. Nicotine content of cigarettes was progressively reduced over 6 months and measures of smoking behavior, as well as nicotine metabolites and tobacco smoke toxicant exposure, CYP2A6 and nicotinic CHRNA5-A3-B4 (rs1051730) genotype were measured. Higher baseline FTCD predicted smoking more cigarettes per day (CPD), higher cotinine and smoke toxicant levels while smoking RNC throughout the study, with no interaction by RNC level. Time to first cigarette (TFC) was associated with differences in compensation. TFC within 10 min was associated with a greater increase in CPD compared to TFC greater than 10 min. Neither rate of nicotine metabolism, nor CYP2A6 or nicotinic receptor genotype, had an effect on the outcome variables of interest. FTCD is associated with overall exposure to nicotine and other constituents of tobacco smoke, while a short TFC is associated with an increased compensatory response after switching to RNC. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Nicotine delivery from the refill liquid to the aerosol via high-power e-cigarette device.

PubMed

Prévôt, Nathalie; de Oliveira, Fabien; Perinel-Ragey, Sophie; Basset, Thierry; Vergnon, Jean-Michel; Pourchez, Jérémie

2017-06-01

To offer an enhanced and well-controlled nicotine delivery from the refill liquid to the aerosol is a key point to adequately satisfy nicotine cravings using electronic nicotine delivery systems (ENDS). A recent high-power ENDS, exhibiting higher aerosol nicotine delivery than older technologies, was used. The particle size distribution was measured using a cascade impactor. The effects of the refill liquid composition on the nicotine content of each size-fraction in the submicron range were investigated. Nicotine was quantified by liquid chromatography coupled with tandem mass spectrometry. Particle size distribution of the airborne refill liquid and the aerosol nicotine demonstrated that the nicotine is equally distributed in droplets regardless of their size. Results also proved that the nicotine concentration in aerosol was significantly lower compared to un-puffed refill liquid. A part of the nicotine may be left in the ENDS upon depletion, and consequently a portion of the nicotine may not be transferred to the user. Thus, new generation high-power ENDS associated with propylene glycol/vegetable glycerin (PG/VG) based solvent were very efficient to generate carrier-droplets containing nicotine molecules with a constant concentration. Findings highlighted that a portion of the nicotine in the refill liquid may not be transferred to the user.

Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily.

PubMed

Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy; McMahon, Lance R

2016-12-01

Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg -1 base weight) from saline. One group received additional nicotine treatment post-session (1.78 mg·kg -1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Daily repeated nicotine treatment produced a time-related increase in saliva cotinine. There was no significant difference in the ED 50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro-β-erythroidine did not. Midazolam produced 0% nicotine-lever responding. The nAChR agonists epibatidine, RTI-36, cytisine and varenicline produced >96% nicotine-lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine-like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. © 2016 The British Pharmacological Society.

Using Basic Principles To Understand Complex Science: Nicotine Smoke Chemistry and Literature Analogies

NASA Astrophysics Data System (ADS)

Seeman, Jeffrey I.

2005-10-01

The Henderson Hasselbalch equation calculates the equilibrium distribution of 50:50 for nicotine in its nonprotonated (free base form), relative to its monoprotonated form, at pH of 8 in dilute aqueous solution. This ratio has then been used in the literature to predict the effect of ammonia compounds in tobacco and in smoke on nicotine pyrolysis and smoke chemistry. Experiments demonstrate that neither the thermal chemistry of tobacco alkaloids nor the transfer of nicotine from tobacco to smoke can be explained by the position of the nonprotonated versus monoprotonated form equilibrium in aqueous extracts of tobacco. The high thermal stability of nicotine in air allows nicotine salts to be converted to nonprotonated nicotine and volatilize during heating prior to any substantial decomposition of the nicotine moiety. In contrast, cocaine hydrochloride is thermally unstable and will rapidly decompose upon heating; cocaine hydrochloride must first be converted to its nonprotonated form prior to heating and volatilization.

Biologically plausible particulate air pollution mortality concentration-response functions.

PubMed Central

Roberts, Steven

2004-01-01

In this article I introduce an alternative method for estimating particulate air pollution mortality concentration-response functions. This method constrains the particulate air pollution mortality concentration-response function to be biologically plausible--that is, a non-decreasing function of the particulate air pollution concentration. Using time-series data from Cook County, Illinois, the proposed method yields more meaningful particulate air pollution mortality concentration-response function estimates with an increase in statistical accuracy. PMID:14998745

Chemical Composition and Evaluation of Nicotine, Tobacco Alkaloids, pH and Selected Flavors in e-Cigarette Cartridges and Refill Solutions

PubMed Central

Lisko, Joseph G.; Tran, Hang; Stanfill, Stephen B.; Blount, Benjamin C.; Watson, Clifford H.

2015-01-01

Introduction Electronic cigarette (e-cigarette) use is increasing dramatically in developed countries, but little is known about these rapidly evolving products. This study analyzed and evaluated the chemical composition including nicotine, tobacco alkaloids, pH and flavors in 36 e-liquids brands from four manufacturers. Methods We determined the concentrations of nicotine, alkaloids, and select flavors and measured pH in solutions used in e-cigarettes. E-cigarette products were chosen based upon favorable consumer approval ratings from online review websites. Quantitative analyses were performed using strict quality assurance/quality control (QC) validated methods previously established by our lab for the measurement of nicotine, alkaloids, pH and flavors. Results Three-quarters of the products contained lower measured nicotine levels than the stated label values (6% - 42% by concentration). The pH for e-liquids ranged from 5.1 – 9.1. Minor tobacco alkaloids were found in all samples containing nicotine, and their relative concentrations varied widely among manufacturers. A number of common flavor compounds were analyzed in all e-liquids. Conclusions Free nicotine levels calculated from the measurement of pH correlated with total nicotine content. The direct correlation between the total nicotine concentration and pH suggests that the alkalinity of nicotine drives the pH of e-cigarette solutions. A higher percentage of nicotine exists in the more absorbable free form as total nicotine concentration increases. A number of products contained tobacco alkaloids at concentrations that exceed U.S. Pharmacopeia limits for impurities in nicotine used in pharmaceutical and food products. PMID:25636907

Reinforcing effectiveness of nicotine in nonhuman primates: effects of nicotine dose and history of nicotine self-administration.

PubMed

Kohut, Stephen J; Bergman, Jack

2016-07-01

Despite the high prevalence of nicotine use in humans, robust nicotine self-administration has been difficult to demonstrate in laboratory animals. A parametric analysis of nicotine self-administration was conducted to study its reinforcing effects in nonhuman primates. Adult rhesus macaques (N = 6) self-administered intravenous (IV) nicotine (0.001-0.1 mg/kg) under a fixed-ratio (FR)1 schedule of reinforcement during daily 90-min sessions. Next, the demand function relating drug intake and response cost was determined by increasing the FR across sessions during the availability of each of several unit doses of nicotine (0.0032-0.032 mg/kg/inj). The reinforcing effects of 0.01 mg/kg/inj cocaine and 1 g banana-flavored food pellets were also determined under similar testing conditions. Finally, the nicotine demand function was re-determined after approximately 8 months of daily IV nicotine self-administration. IV nicotine self-administration followed an inverted U-shaped pattern, with the peak number of injections maintained by 0.0032 mg/kg/inj. Self-administration of each reinforcer (food pellets, IV cocaine, and IV nicotine) decreased as FR size increased. Application of the exponential model of demand showed that demand elasticity for nicotine was (1) dose-dependent and lowest for 0.0032 mg/kg/inj; (2) for 0.0032 mg/kg/inj, similar to that of food pellets and significantly higher than cocaine; and (3) decreased after 8 months of daily nicotine self-administration. These data show that, though high levels of nicotine self-administration can be achieved under simple FR schedules in nonhuman primates, its reinforcing effectiveness is dose-related but limited and may increase over time.

Comparison of the impact of the Tobacco Heating System 2.2 and a cigarette on indoor air quality.

PubMed

Mitova, Maya I; Campelos, Pedro B; Goujon-Ginglinger, Catherine G; Maeder, Serge; Mottier, Nicolas; Rouget, Emmanuel G R; Tharin, Manuel; Tricker, Anthony R

2016-10-01

The impact of the Tobacco Heating System 2.2 (THS 2.2) on indoor air quality was evaluated in an environmentally controlled room using ventilation conditions recommended for simulating "Office", "Residential" and "Hospitality" environments and was compared with smoking a lit-end cigarette (Marlboro Gold) under identical experimental conditions. The concentrations of eighteen indoor air constituents (respirable suspended particles (RSP) < 2.5 μm in diameter), ultraviolet particulate matter (UVPM), fluorescent particulate matter (FPM), solanesol, 3-ethenylpyridine, nicotine, 1,3-butadiene, acrylonitrile, benzene, isoprene, toluene, acetaldehyde, acrolein, crotonaldehyde, formaldehyde, carbon monoxide, nitrogen oxide, and combined oxides of nitrogen) were measured. In simulations evaluating THS 2.2, the concentrations of most studied analytes did not exceed the background concentrations determined when non-smoking panelists were present in the environmentally controlled room under equivalent conditions. Only acetaldehyde and nicotine concentrations were increased above background concentrations in the "Office" (3.65 and 1.10 μg/m(3)), "Residential" (5.09 and 1.81 μg/m(3)) and "Hospitality" (1.40 and 0.66 μg/m(3)) simulations, respectively. Smoking Marlboro Gold resulted in greater increases in the concentrations of acetaldehyde (58.8, 83.8 and 33.1 μg/m(3)) and nicotine (34.7, 29.1 and 34.6 μg/m(3)) as well as all other measured indoor air constituents in the "Office", "Residential" and "Hospitality" simulations, respectively. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Nicotine is Chemotactic for Neutrophils and Enhances Neutrophil Responsiveness to Chemotactic Peptides

NASA Astrophysics Data System (ADS)

Totti, Noel; McCusker, Kevin T.; Campbell, Edward J.; Griffin, Gail L.; Senior, Robert M.

1984-01-01

Neutrophils contribute to chronic bronchitis and pulmonary emphysema associated with cigarette smoking. Nicotine was found to be chemotactic for human neutrophils but not monocytes, with a peak activity at ~ 31 micromolar. In lower concentrations (comparable to those in smokers' plasma), nicotine enhanced the response of neutrophils to two chemotactic peptides. In contrast to most other chemoattractants for neutrophils, however, nicotine did not affect degranulation or superoxide production. Nicotine thus may promote inflammation and consequent lung injury in smokers.

Airborne Nicotine, Secondhand Smoke, and Precursors to Adolescent Smoking.

PubMed

McGrath, Jennifer J; Racicot, Simon; Okoli, Chizimuzo T C; Hammond, S Katharine; O'Loughlin, Jennifer

2018-01-01

Secondhand smoke (SHS) directly increases exposure to airborne nicotine, tobacco's main psychoactive substance. When exposed to SHS, nonsmokers inhale 60% to 80% of airborne nicotine, absorb concentrations similar to those absorbed by smokers, and display high levels of nicotine biomarkers. Social modeling, or observing other smokers, is a well-established predictor of smoking during adolescence. Observing smokers also leads to increased pharmacological exposure to airborne nicotine via SHS. The objective of this study is to investigate whether greater exposure to airborne nicotine via SHS increases the risk for smoking initiation precursors among never-smoking adolescents. Secondary students ( N = 406; never-smokers: n = 338, 53% girls, mean age = 12.9, SD = 0.4) participated in the AdoQuest II longitudinal cohort. They answered questionnaires about social exposure to smoking (parents, siblings, peers) and known smoking precursors (eg, expected benefits and/or costs, SHS aversion, smoking susceptibility, and nicotine dependence symptoms). Saliva and hair samples were collected to derive biomarkers of cotinine and nicotine. Adolescents wore a passive monitor for 1 week to measure airborne nicotine. Higher airborne nicotine was significantly associated with greater expected benefits ( R 2 = 0.024) and lower expected costs ( R 2 = 0.014). Higher social exposure was significantly associated with more temptation to try smoking ( R 2 = 0.025), lower aversion to SHS ( R 2 = 0.038), and greater smoking susceptibility ( R 2 = 0.071). Greater social exposure was significantly associated with more nicotine dependence symptoms; this relation worsened with higher nicotine exposure (cotinine R 2 = 0.096; airborne nicotine R 2 = 0.088). Airborne nicotine exposure via SHS is a plausible risk factor for smoking initiation during adolescence. Public health implications include limiting airborne nicotine through smoking bans in homes and cars, in addition to stringent restrictions

Using nicotine in scalp hair to assess maternal passive exposure to tobacco smoke.

PubMed

Li, Zhenjiang; Li, Zhiwen; Zhang, Jingxu; Huo, Wenhua; Zhu, Yibing; Xie, Jing; Lu, Qun; Wang, Bin

2017-03-01

Quantifying population exposure level to tobacco smoke is important for investigating its adverse effects on human health. We aimed to investigate the feasibility and application of using population hair concentrations of nicotine and cotinine to indicate their exposure level to tobacco smoke among pregnant women. Our study recruited 256 mothers who delivered healthy babies and collected their hair samples from scalp, of which 172 mothers were self-reported non-passive smokers and the other 84 mothers were self-reported passive smokers. We analyzed nicotine and cotinine concentrations of the hair section grown during the early pregnancy. The linear relationship between cotinine and nicotine was developed and validated by internal cross-validation method. Our results revealed that self-reported passive smokers had higher concentrations of nicotine [2.08 (1.00-4.46) ng/mg hair, i.e. median value (inter-quartile range)] and cotinine [0.063 (0.041-0.148) ng/mg hair] than non-passive smokers [1.35 (0.58-2.59) ng/mg hair of nicotine and 0.049 (0.022-0.087) ng/mg hair of cotinine, respectively]. There existed a linear regression model between hair cotinine and nicotine concentrations, i.e. [cotinine] = 0.024 × [nicotine]+0.0184 (R 2  = 0.756) for this population. The internal cross-validation squared correlation coefficient slightly increased from 0.689 to 0.734 with the training subjects varying from 20% to 90%, suggesting that this regression model had high robustness and predictive accuracy. It was concluded that nicotine in maternal hair can evaluate the hair cotinine level and reflect maternal passive exposure level to ambient tobacco smoke with high sensitivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical Composition and Evaluation of Nicotine, Tobacco Alkaloids, pH, and Selected Flavors in E-Cigarette Cartridges and Refill Solutions.

PubMed

Lisko, Joseph G; Tran, Hang; Stanfill, Stephen B; Blount, Benjamin C; Watson, Clifford H

2015-10-01

Electronic cigarette (e-cigarette) use is increasing dramatically in developed countries, but little is known about these rapidly evolving products. This study analyzed and evaluated the chemical composition including nicotine, tobacco alkaloids, pH, and flavors in 36 e-liquids brands from 4 manufacturers. We determined the concentrations of nicotine, alkaloids, and select flavors and measured pH in solutions used in e-cigarettes. E-cigarette products were chosen based upon favorable consumer approval ratings from online review websites. Quantitative analyses were performed using strict quality assurance/quality control validated methods previously established by our lab for the measurement of nicotine, alkaloids, pH, and flavors. Three-quarters of the products contained lower measured nicotine levels than the stated label values (6%-42% by concentration). The pH for e-liquids ranged from 5.1-9.1. Minor tobacco alkaloids were found in all samples containing nicotine, and their relative concentrations varied widely among manufacturers. A number of common flavor compounds were analyzed in all e-liquids. Free nicotine levels calculated from the measurement of pH correlated with total nicotine content. The direct correlation between the total nicotine concentration and pH suggests that the alkalinity of nicotine drives the pH of e-cigarette solutions. A higher percentage of nicotine exists in the more absorbable free form as total nicotine concentration increases. A number of products contained tobacco alkaloids at concentrations that exceed U.S. pharmacopeia limits for impurities in nicotine used in pharmaceutical and food products. © Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Nicotinic acid modulates Legionella pneumophila gene expression and induces virulence traits.

PubMed

Edwards, Rachel L; Bryan, Andrew; Jules, Matthieu; Harada, Kaoru; Buchrieser, Carmen; Swanson, Michele S

2013-03-01

In response to environmental fluctuations or stresses, bacteria can activate transcriptional and phenotypic programs to coordinate an adaptive response. The intracellular pathogen Legionella pneumophila converts from a noninfectious replicative form to an infectious transmissive form when the bacterium encounters alterations in either amino acid concentrations or fatty acid biosynthesis. Here, we report that L. pneumophila differentiation is also triggered by nicotinic acid, a precursor of the central metabolite NAD(+). In particular, when replicative L. pneumophila are treated with 5 mM nicotinic acid, the bacteria induce numerous transmissive-phase phenotypes, including motility, cytotoxicity toward macrophages, sodium sensitivity, and lysosome avoidance. Transcriptional profile analysis determined that nicotinic acid induces the expression of a panel of genes characteristic of transmissive-phase L. pneumophila. Moreover, an additional 213 genes specific to nicotinic acid treatment were altered. Although nearly 25% of these genes lack an assigned function, the gene most highly induced by nicotinic acid treatment encodes a putative major facilitator superfamily transporter, Lpg0273. Indeed, lpg0273 protects L. pneumophila from toxic concentrations of nicotinic acid as judged by analyzing the growth of the corresponding mutant. The broad utility of the nicotinic acid pathway to couple central metabolism and cell fate is underscored by this small metabolite's modulation of gene expression by diverse microbes, including Candida glabrata, Bordetella pertussis, Escherichia coli, and L. pneumophila.

Development of a rectal nicotine delivery system for the treatment of ulcerative colitis.

PubMed

Dash, A K; Gong, Z; Miller, D W; Huai-Yan, H; Laforet, J

1999-11-10

The aims of this investigation were: i. to develop a rectal nicotine delivery system with bioadhesives for the treatment of ulcerative colitis and ii. to evaluate nicotine transport and cytotoxicity of the delivery system using Caco-2 cell culture systems. Rectal nicotine suppository formulations were prepared in semi-synthetic glyceride bases (Suppocire AM and AI, Gattefosse Inc.) by fusion method. The in vitro release of nicotine was carried out in modified USP dissolution apparatus 1. Differential scanning calorimetry (DSC) and powder X-ray diffraction were used to study the polymorphic changes if any in the formulations. An LC method was used for the assay of nicotine. The effect of bioadhesives (glyceryl monooleate (GMO), and Carbopol) on the nicotine flux was evaluated using Caco-2 cell permeability studies and Caco-2 cell viability was determined using the MTT toxicity assay. In vitro release studies indicated that the low melting AI base was superior to that of the AM base. Presence of GMO in the formulation enhanced the release of nicotine whereas Carbopol showed an opposite effect. The enhanced release of nicotine in the presence of GMO was found to be partly due to the melting point lowering effect of this compound. Caco-2 cell absorption studies showed that there was a decrease in the flux of nicotine in the presence of both the bioadhesives. The flux of the fluorescein marker which is used to study the integrity of the cell monolayers was found to be slightly higher only in the presence of 10% (w/w) Carbopol. Nicotine, Carbopol, and GMO do not have any cytotoxic effect on these cell monolayers within the concentration range used in the formulations. Rectal nicotine formulations containing bioadhesives were developed and characterized. Both in vitro release and cell culture studies have indicated that one can manipulate the nicotine release from these rectal delivery systems by incorporation of various bioadhesives or the use of different bases in the

Effect of urinary pH and nicotine excretion rate on plasma nicotine during cigarette smoking and chewing nicotine gum

PubMed Central

Feyerabend, C.; Russell, M. A. H.

1978-01-01

1 Plasma nicotine levels produced by chewing nicotine gum were compared with those obtained by cigarette smoking under conditions of controlled urinary pH. 2 Although absorption was slower, plasma levels comparable to cigarette smoking were built up on 4 mg (but not 2 mg) nicotine gum. 3 Urinary excretion of nicotine was influenced markedly by pH and the rate of urine flow. 4 Plasma nicotine was higher under alkaline compared to acidic conditions (P < 0.001) but the rate of urinary nicotine excretion appeared to have little effect on the plasma level.

Purification of L-( sup 3 H) Nicotine eliminates low affinity binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romm, E.; Marks, M.J.; Collins, A.C.

1990-01-01

Some studies of L-({sup 3}H) nicotine binding to rodent and human brain tissue have detected two binding sites as evidenced by nonlinear Scatchard plots. Evidence presented here indicated that the low affinity binding site is not stereospecific, is not inhibited by low concentrations of cholinergic agonists and is probably due to breakdown products of nicotine since purification of the L-({sup 3}H)nicotine eliminates the low affinity site.

Intracellular pH in rat isolated superior cervical ganglia in relation to nicotine-depolarization and nicotine-uptake

PubMed Central

Brown, D. A.; Halliwell, J. V.

1972-01-01

1. The intracellular pH (pHi) of rat isolated superior cervical ganglia incubated in normal Krebs solution (pHo=7·37) was estimated to be 7·33 from the uptake of a weak acid, 14C-5,5-dimethyloxazolidine-2,4-dione (DMO). Addition of 30 μM nicotine for 30 min reduced the DMO-estimated pHi by 0·15 units to 7·18. This effect was prevented by hexamethonium (2·5 mM) or by depolarizing the ganglion with K+ (124 mM). 2. 3H-Nicotine (30 μM) was concentrated within the ganglia to an intracellular/extracellular concentration ratio (Ci/Co) of 5·54 in normal Krebs solution and 4·61 in 2·5 mM hexamethonium. This would suggest an intracellular pH of 6·54 and 6·63 respectively. In ganglia previously depolarized by K+ the corresponding values for Ci/Co were 4·02 (minus hexamethonium, estimated pHi 6·95) and 4·17 (plus hexamethonium, estimated pHi 6·94). 3. A multicompartment cell interior comprising an acid cytoplasm (pH∼6·6) and more alkaline nucleus and mitochondria is proposed to explain the difference between the values of pHi estimated from the uptake of DMO and nicotine. It is suggested that the fall in pHi during nicotine-depolarization results from metabolic stimulation following Na+ entry. PMID:5048652

Spanish adaptation of the NDSS (Nicotine Dependence Syndrome Scale) and assessment of nicotine-dependent individuals at primary care health centers in Spain.

PubMed

Becoña, Elisardo; López, Ana; Fernández del Río, Elena; Míguez, Ma Carmen; Castro, Josefina

2010-11-01

The availability of adequate instruments for the assessment of nicotine dependence is an important factor that is relevant in the area of tobacco addiction. In this study, we present a Spanish validation of the Nicotine Dependence Syndrome Scale (NDSS) (Shiffman, Waters, & Hickcox, 2004). The sample was composed ofpatients, all daily smokers, who visited their General Practitioner (GP) at five Primary Health Care Centers in different cities of Spain (N = 637). The results indicated adequate reliability for the general factor that assesses nicotine dependence (NDSS-Total) (Cronbach's alpha = .76). Factor analysis confirms the five factors of the original validation: Drive, Continuity, Stereotypy, Priority, and Tolerance. It must be noted that reliability is adequate for the first, and moderate or low for the rest. The NDSS-T and its scales correlate significantly with the Fagerström Test for Nicotine Dependence (FTND), with the nicotine dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) as assessed through the Structured Clinical Interview for DSM-IV (SCID), with carbon monoxide levels in expired air (CO), and with the number of cigarettes smoked. The ROC curve indicates that the NDSS-T has a score of .79 which is under the curve (.69 for the FTND), thus the prediction of nicotine dependence is adequate. We conclude that this instrument is useful (in terms of its total score NDSS-T) for assessing nicotine dependence for Spanish smokers (in Spain), as has been found in other countries, language groups, and cultures.

A new air quality monitoring and early warning system: Air quality assessment and air pollutant concentration prediction.

PubMed

Yang, Zhongshan; Wang, Jian

2017-10-01

Air pollution in many countries is worsening with industrialization and urbanization, resulting in climate change and affecting people's health, thus, making the work of policymakers more difficult. It is therefore both urgent and necessary to establish amore scientific air quality monitoring and early warning system to evaluate the degree of air pollution objectively, and predict pollutant concentrations accurately. However, the integration of air quality assessment and air pollutant concentration prediction to establish an air quality system is not common. In this paper, we propose a new air quality monitoring and early warning system, including an assessment module and forecasting module. In the air quality assessment module, fuzzy comprehensive evaluation is used to determine the main pollutants and evaluate the degree of air pollution more scientifically. In the air pollutant concentration prediction module, a novel hybridization model combining complementary ensemble empirical mode decomposition, a modified cuckoo search and differential evolution algorithm, and an Elman neural network, is proposed to improve the forecasting accuracy of six main air pollutant concentrations. To verify the effectiveness of this system, pollutant data for two cities in China are used. The result of the fuzzy comprehensive evaluation shows that the major air pollutants in Xi'an and Jinan are PM 10 and PM 2.5 respectively, and that the air quality of Xi'an is better than that of Jinan. The forecasting results indicate that the proposed hybrid model is remarkably superior to all benchmark models on account of its higher prediction accuracy and stability. Copyright © 2017 Elsevier Inc. All rights reserved.

Nicotine Delivery to Rats via Lung Alveolar Region-Targeted Aerosol Technology Produces Blood Pharmacokinetics Resembling Human Smoking

PubMed Central

2013-01-01

Introduction: Nicotine is a heavily used addictive drug acquired through smoking tobacco. Nicotine in cigarette smoke is deposited and absorbed in the lungs, which results in a rapidly peaked slowly declining arterial concentration. This pattern plays an important role in initiation of nicotine addiction. Methods: A method and device were developed for delivering nicotine to rodents with lung alveolar region-targeted aerosol technology. The dose of delivery can be controlled by the nicotine aerosol concentration and duration of exposure. Results: Our data showed that, in the breathing zone of the nose-only exposure chamber, the aerosol droplet size distribution was within the respirable diameter range. Rats were exposed to nicotine aerosol for 2min. The arterial blood nicotine concentration reached 43.2±15.7ng/ml (mean ± SD) within 1–4min and declined over the next 20min, closely resembling the magnitude and early pharmacokinetics of a human smoking a cigarette. The acute inhalation toxicity of nicotine: LC50 = 2.3mg/L was determined; it was affected by pH, suggesting that acidification decreases nicotine absorption and/or bioavailability. Conclusions: A noninvasive method and toolkit were developed for delivering nicotine to rodents that enable rapid delivery of a controllable amount of nicotine into the systemic circulation and brain-inducing dose-dependent pharmacological effects, even a lethal dose. Aerosol inhalation can produce nicotine kinetics in both arterial and venous blood resembling human smoking. This method can be applied to studies of the effects of chronic intermittent nicotine exposure, nicotine addiction, toxicology, tobacco-related diseases, teratogenicity, and for discovery of pharmacological therapeutics. PMID:23239844

Electronic nicotine delivery systems: regulatory and safety challenges: Singapore perspective.

PubMed

Cheah, Nuan Ping; Chong, Norman Wee Lin; Tan, Jing; Morsed, Faridatul Akmam; Yee, Shen Kuan

2014-03-01

Many electronic nicotine delivery systems (ENDS) are marketed as safer tobacco alternative products or effective cessation therapies. ENDS samples were evaluated for design features, including nicotine and glycols content. This could be useful in developing a legal framework to handle ENDS. Identification of the nicotine, glycerol and propylene glycol (PPG) contents was conducted using gas chromatography mass spectrometry with quantification performed using flame ionisation techniques. Varying nicotine amounts were found in ENDS cartridges which were labelled with the same concentration. Chemicals such as PPG and glycerol were found to be present in the nicotine-containing liquid of the cartridges. ENDS varied in their contents and packaging information. Limited information was available on the contents of nicotine and other chemicals present in a variety of ENDS sampled. Based on samples tested in this study, many contain misleading information on product ingredients. The results show poor consistency between actual nicotine content analysed on ENDS cartridges and the amount labelled. These findings raise safety and efficacy concerns for current and would-be recreational users or those trying to quit smoking.

Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints.

PubMed

Phillips, Blaine; Titz, Bjoern; Kogel, Ulrike; Sharma, Danilal; Leroy, Patrice; Xiang, Yang; Vuillaume, Grégory; Lebrun, Stefan; Sciuscio, Davide; Ho, Jenny; Nury, Catherine; Guedj, Emmanuel; Elamin, Ashraf; Esposito, Marco; Krishnan, Subash; Schlage, Walter K; Veljkovic, Emilija; Ivanov, Nikolai V; Martin, Florian; Peitsch, Manuel C; Hoeng, Julia; Vanscheeuwijck, Patrick

2017-11-01

While the toxicity of the main constituents of electronic cigarette (ECIG) liquids, nicotine, propylene glycol (PG), and vegetable glycerin (VG), has been assessed individually in separate studies, limited data on the inhalation toxicity of them is available when in mixtures. In this 90-day subchronic inhalation study, Sprague-Dawley rats were nose-only exposed to filtered air, nebulized vehicle (saline), or three concentrations of PG/VG mixtures, with and without nicotine. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared with vehicle exposure, the PG/VG aerosols showed only very limited biological effects with no signs of toxicity. Addition of nicotine to the PG/VG aerosols resulted in effects in line with nicotine effects observed in previous studies, including up-regulation of xenobiotic enzymes (Cyp1a1/Fmo3) in the lung and metabolic effects, such as reduced serum lipid concentrations and expression changes of hepatic metabolic enzymes. No toxicologically relevant effects of PG/VG aerosols (up to 1.520  mg PG/L + 1.890 mg VG/L) were observed, and no adverse effects for PG/VG/nicotine were observed up to 438/544/6.6 mg/kg/day. This study demonstrates how complementary systems toxicology analyses can reveal, even in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of nicotine and nicotine expectancy on attentional bias for emotional stimuli.

PubMed

Adams, Sally; Attwood, Angela S; Munafò, Marcus R

2015-06-01

Nicotine's effects on mood are thought to enhance its addictive potential. However, the mechanisms underlying the effects of nicotine on affect regulation have not been reliably demonstrated in human laboratory studies. We investigated the effects of nicotine abstinence (Experiment 1), and nicotine challenge and expectancy (Experiment 2) on attentional bias towards facial emotional stimuli differing in emotional valence. In Experiment 1, 46 nicotine-deprived smokers were randomized to either continue to abstain from smoking or to smoke immediately before testing. In Experiment 2, 96 nicotine-deprived smokers were randomized to smoke a nicotinized or denicotinized cigarette and to be told that the cigarette did or did not contain nicotine. In both experiments participants completed a visual probe task, where positively valenced (happy) and negatively valenced (sad) facial expressions were presented, together with neutral facial expressions. In Experiment 1, there was evidence of an interaction between probe location and abstinence on reaction time, indicating that abstinent smokers showed an attentional bias for neutral stimuli. In Experiment 2, there was evidence of an interaction between probe location, nicotine challenge and expectation on reaction time, indicating that smokers receiving nicotine, but told that they did not receive nicotine, showed an attentional bias for emotional stimuli. Our data suggest that nicotine abstinence appears to disrupt attentional bias towards emotional facial stimuli. These data provide support for nicotine's modulation of attentional bias as a central mechanism for maintaining affect regulation in cigarette smoking. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Nicotinic plant poisoning.

PubMed

Schep, Leo J; Slaughter, Robin J; Beasley, D Michael G

2009-09-01

A wide range of plants contain nicotinic and nicotinic-like alkaloids. Of this diverse group, those that have been reported to cause human poisoning appear to have similar mechanisms of toxicity and presenting patients therefore have comparable toxidromes. This review describes the taxonomy and principal alkaloids of plants that contain nicotinic and nicotinic-like alkaloids, with particular focus on those that are toxic to humans. The toxicokinetics and mechanisms of toxicity of these alkaloids are reviewed and the clinical features and management of poisoning due to these plants are described. This review was compiled by systematically searching OVID MEDLINE and ISI Web of Science. This identified 9,456 papers, excluding duplicates, all of which were screened. Reviewed plants and their principal alkaloids. Plants containing nicotine and nicotine-like alkaloids that have been reported to be poisonous to humans include Conium maculatum, Nicotiana glauca and Nicotiana tabacum, Laburnum anagyroides, and Caulophyllum thalictroides. They contain the toxic alkaloids nicotine, anabasine, cytisine, n-methylcytisine, coniine, n-methylconiine, and gamma-coniceine. These alkaloids act agonistically at nicotinic-type acetylcholine (cholinergic) receptors (nAChRs). The nicotinic-type acetylcholine receptor can vary both in its subunit composition and in its distribution within the body (the central and autonomic nervous systems, the neuromuscular junctions, and the adrenal medulla). Agonistic interaction at these variable sites may explain why the alkaloids have diverse effects depending on the administered dose and duration of exposure. Nicotine and nicotine-like alkaloids are absorbed readily across all routes of exposure and are rapidly and widely distributed, readily traversing the blood-brain barrier and the placenta, and are freely distributed in breast milk. Metabolism occurs predominantly in the liver followed by rapid renal elimination. Following acute exposure

Measuring Concentrations of Particulate 140La in the Air

DOE PAGES

Okada, Colin E.; Kernan, Warnick J.; Keillor, Martin E.; ...

2016-05-01

Air sampling systems were deployed to measure the concentration of radioactive material in the air during the Full-Scale Radiological Dispersal Device experiments. The air samplers were positioned 100-600 meters downwind of the release point. The filters were collected immediately and analyzed in the field. Quantities for total activity collected on the air filters are reported along with additional information to compute the average or integrated air concentrations.

Nicotine and cotinine in infants dying from sudden infant death syndrome.

PubMed

Bajanowski, T; Brinkmann, B; Mitchell, E A; Vennemann, M M; Leukel, H W; Larsch, K-P; Beike, J

2008-01-01

The aim of this component of the German Study on Sudden Infant Death was to determine (1) nicotine concentrations in hair (NCH), as a marker of long standing exposure to tobacco, (2) cotinine concentrations in pericardial fluid (CCP) and (3) cotinine concentrations in liquor cerebrospinalis (CCL), the latter measures being markers of recent exposure to tobacco in the last few hours of life. The results obtained were compared with data on parental smoking revealed from interviews. In 100 cases of sudden infant death syndrome, material was taken at autopsy to determine NCH. In 41 cases, NCH and CCP, and in 70 cases, NCH and CCL were determined. Infants of mothers who stated having smoked during pregnancy had higher NCH than infants of non-smoking mothers (p = 0.008). Furthermore, there was a weak but statistically significant relationship between NCH's and the daily cigarette consumption of the mother during pregnancy (n = 64, r = 0.24, p = 0.05). In 43% of infants, nicotine could be detected in their hair, although the mothers had said at the interview that they did not smoke during pregnancy. On the other hand, in 33% of infants whose mother stated they had smoked during pregnancy nicotine was not detectable in the infant's hair. CCP's were strongly correlated with CCL's (r = 0.62, p = 0.0027). For this reason, both parameters were treated as equivalent for the detection of tobacco smoke exposure in the last hours before death. The influence of breast-feeding was evaluated by comparison of the nicotine concentrations in breast fed and non-breast-fed infants from smokers and non-smokers. Fivefold higher nicotine concentrations were determined in non-breast-fed infants of parents who smoked as compared to all other groups. It can be concluded that nicotine intake by passive smoking is much more important than by breast-feeding. We conclude that both interview data and biochemical measures should be sought to understand the true exposure to tobacco smoke.

Concentrations of the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in sidestream cigarette smoke increase after release into indoor air: results from unpublished tobacco industry research.

PubMed

Schick, Suzaynn F; Glantz, Stanton

2007-08-01

Research has shown that the toxicity of sidestream cigarette smoke, the primary constituent of secondhand smoke, increases over time. To find potential mechanisms that would explain the increase in sidestream smoke toxicity over time, we analyzed unpublished research reports from Philip Morris Co. using the internal tobacco industry documents now available at the University of California San Francisco Legacy Tobacco Documents Library and other Web sites. Unpublished research from Philip Morris Tobacco Company shows that 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone (NNK), a highly carcinogenic tobacco-specific nitrosamine, can form in sidestream cigarette smoke after it has been released into ambient air. In experiments done between 1983 and 1997, Philip Morris scientists measured the concentration of NNK in sidestream smoke in a sealed stainless steel test chamber at initial particle concentrations of 24 mg/m(3) over the course of 6 to 18 h. They repeatedly showed that airborne NNK concentrations in sidestream cigarette smoke can increase by 50% to 200% per hour during the first 6 h after cigarettes are extinguished. Two experiments done in a real office showed that NNK concentrations increase for the first 2 h after cigarettes are extinguished. If NNK formation also occurs in the lower smoke concentrations observed in real smoking environments, these results suggest that nitrosation of nicotine and/or nicotine breakdown products in aging secondhand smoke is a significant contributor to nitrosamine exposure in humans.

Nicotine affects protein complex rearrangement in Caenorhabditis elegans cells.

PubMed

Sobkowiak, Robert; Zielezinski, Andrzej; Karlowski, Wojciech M; Lesicki, Andrzej

2017-10-01

Nicotine may affect cell function by rearranging protein complexes. We aimed to determine nicotine-induced alterations of protein complexes in Caenorhabditis elegans (C. elegans) cells, thereby revealing links between nicotine exposure and protein complex modulation. We compared the proteomic alterations induced by low and high nicotine concentrations (0.01 mM and 1 mM) with the control (no nicotine) in vivo by using mass spectrometry (MS)-based techniques, specifically the cetyltrimethylammonium bromide (CTAB) discontinuous gel electrophoresis coupled with liquid chromatography (LC)-MS/MS and spectral counting. As a result, we identified dozens of C. elegans proteins that are present exclusively or in higher abundance in either nicotine-treated or untreated worms. Based on these results, we report a possible network that captures the key protein components of nicotine-induced protein complexes and speculate how the different protein modules relate to their distinct physiological roles. Using functional annotation of detected proteins, we hypothesize that the identified complexes can modulate the energy metabolism and level of oxidative stress. These proteins can also be involved in modulation of gene expression and may be crucial in Alzheimer's disease. The findings reported in our study reveal putative intracellular interactions of many proteins with the cytoskeleton and may contribute to the understanding of the mechanisms of nicotinic acetylcholine receptor (nAChR) signaling and trafficking in cells.

Evaluation of a novel nicotine inhaler device: part 1--arterial and venous pharmacokinetics.

PubMed

Moyses, Chris; Hearn, Alex; Redfern, Andrew

2015-01-01

In the United Kingdom, licensed nicotine-containing products can be recommended to reduce the harm associated with smoking. Many smokers find currently available nicotine replacement products unsatisfactory. The arterial and venous pharmacokinetics (PK) of nicotine delivered via a novel inhaler device were determined. Results are reported for Parts A (N = 18) and C (N = 18) of a 4-part (A-D) Phase I study. Participants (18-55 years, ≥ 10 cigarettes/day, smoking within 1 hr of waking, expired carbon monoxide >10 ppm on screening) orally inhaled 2 single doses of nicotine (2 of 3 dose levels [0.22, 0.45, and 0.67 mg]) (Part A) and repeated hourly doses of 0.67 mg nicotine for 12 hr (Part C), via the novel device. Arterial and venous PK and tolerability were assessed. In Part A, mean arterial plasma nicotine concentrations at 2 min after the start of inhalation were 1.10, 2.06, and 2.59 ng/mL for the 0.22, 0.45, and 0.67 mg doses, respectively. Mean maximum arterial plasma nicotine concentrations (C(max)) were 2.11, 3.73, and 4.38 ng/mL and mean times to C(max) were 10.2, 7.3, and 6.5 min after the start of inhalation for the 0.22, 0.45, and 0.67 mg doses, respectively. In Part C, the mean pre- and postdose venous plasma nicotine concentration increased steadily and fluctuated in the range 8-10 mg/mL after 9 hr. The novel device was well tolerated; most adverse events were mild. The novel inhaler device delivers nicotine rapidly into the systemic circulation and offers a viable alternative to cigarettes for those finding it difficult to quit the behavioral and sensorial aspects of smoking. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.

Evaluation of nicotine in tobacco-free-nicotine commercial products.

PubMed

Hellinghausen, Garrett; Lee, Jauh T; Weatherly, Choyce A; Lopez, Diego A; Armstrong, Daniel W

2017-06-01

Recently, a variety of new tobacco-free-nicotine, TFN, products have been commercialized as e-liquids. Tobacco-derived nicotine contains predominantly (S)-(-)-nicotine, whereas TFN products may not. The TFN products are said to be cleaner, purer substances, devoid of toxic components that come from the tobacco extraction process. A variety of commercial tobacco and TFN products were analyzed to identify the presence and composition of each nicotine enantiomer. A rapid and effective enantiomeric separation of nicotine has been developed using a modified macrocyclic glycopeptide bonded to superficially porous particles. The enantiomeric assay can be completed in <2 min with high resolution and accuracy using high performance liquid chromatography with electrospray ionization mass spectrometry. The results of this study suggest the need for pharmacological studies of (R)-(+)-nicotine, which is present in much greater quantities in commercial TFN products compared to commercial tobacco-derived products. Such studies are required by the FDA for new enantiomeric pharmacological products. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Nicotine content of electronic cigarettes, its release in vapour and its consistency across batches: regulatory implications.

PubMed

Goniewicz, Maciej L; Hajek, Peter; McRobbie, Hayden

2014-03-01

Electronic cigarettes (EC) may have a potential for public health benefit as a safer alternative to smoking, but questions have been raised about whether EC should be licensed as a medicine, with accurate labelling of nicotine content. This study determined the nicotine content of the cartridges of the most popular EC brands in the United Kingdom and the nicotine levels they deliver in the vapour, and estimated the safety and consistency of nicotine delivery across batches of the same product as a proxy for quality control for individual brands and within the industry. We studied five UK brands (six products) with high internet popularity. Two samples of each brand were purchased 4 weeks apart, and analysed for nicotine content in the cartridges and nicotine delivery in vapour. The nicotine content of cartridges within the same batch varied by up to 12% relative standard deviation (RSD) and the mean difference between different batches of the same brand ranged from 1% [95% confidence interval (CI) = -5 to 7%] to 20% (95% CI=14-25%) for five brands and 31% (95% CI=21-39%) for the sixth. The puffing schedule used in this study vaporized 10-81% of the nicotine present in the cartridges. The nicotine delivery from 300 puffs ranged from ∼2 mg to ∼15 mg and was not related significantly to the variation of nicotine content in e-liquid (r=0.06, P=0.92). None of the tested products allowed access to e-liquid or produced vapour nicotine concentrations as high as conventional cigarettes. There is very little risk of nicotine toxicity from major electronic cigarette (EC) brands in the United Kingdom. Variation in nicotine concentration in the vapour from a given brand is low. Nicotine concentration in e-liquid is not well related to nicotine in vapour. Other EC brands may be of lower quality and consumer protection regulation needs to be implemented, but in terms of accuracy of labelling of nicotine content and risks of nicotine overdose, regulation over and above

[A preliminary study on the autophagy level of human periodontal ligament cells regulated by nicotine].

PubMed

Yang, Du; Shuai, Yuan; Zhifei, Zhou; Lizheng, Wu; Lulu, Wang; Xing'an, Wu; Xiaojing, Wang

2017-04-01

To explore the effect of nicotine on the autophagy level of human periodontal ligament cells (hPDLCs). Periodontal tissues collected from premolars for orthodontic treatment reasons were used to culture hPDLCs. Western blot analysis was performed to test the most optimal time and concentration of nicotine on the autophagy level of the hPDLCs. Transmission electron microscope and immunofluorescence observation were carried out to detect the form of autophagosomes and expression of autophagy related protein LC3 in hPDLCs under this optimal condition. Protein expression of LC3Ⅱ was up regulated with the 12 h nicotine stimulating. Besides that, the up regulation of the protein expression of LC3Ⅱ was concentration dependent and nicotine with a concentration of 1×10⁻⁵ mol·L⁻¹ was the most optimal condition. Transmission electron microscope and immunofluorescence observations indicated that nicotine would activate the autophagy level of hPDLCs by increasing the number of autophagosomes and up regulating the expression of autophagy related protein LC3. Nicotine could increase autophagy level of hPDLCs, thus affecting the occurrence and development of smoking related periodontitis.

The role of nicotinic receptor alpha 7 subunits in nicotine discrimination.

PubMed

Stolerman, I P; Chamberlain, S; Bizarro, L; Fernandes, C; Schalkwyk, L

2004-03-01

The subtypes of nicotinic receptors at which the behavioural effects of nicotine originate are not fully understood. The experiments described here use mice lacking the alpha7 subunit of nicotinic receptors to investigate the role of alpha7-containing receptors in nicotine discrimination. Wild-type and alpha7-knockout mice were trained in a two-lever nicotine discrimination procedure using a tandem schedule of food reinforcement. Mutant mice exhibited baseline rates of lever-pressing as low as 52.2% of rates in wild-type controls (n=21-24). Mutant and wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) at a similar rate (n=10-12) and reached similar final levels of accuracy (71.9 +/- 4.4% and 90.8 +/- 3.1% after 60 training sessions for 0.4 and 0.8 mg/kg training doses, respectively, in mutant mice, as compared with 75.0 +/- 6.5% and 87.6 +/- 4.8% for wild types). The genotypes exhibited similar steep dose-response curves for nicotine discrimination. In both genotypes, dose-response curves for mice trained with 0.8 mg/kg of nicotine were displaced three- to four-fold to the right as compared with those for the mice trained with the smaller dose. The predominant effect of nicotine on the overall rate of responding was a reduction at the largest doses tested and there was no difference between the genotypes. The results suggest that nicotinic receptors containing the alpha7 subunit do not contribute to the discriminative stimulus or response-rate-depressant effects of nicotine, although they may regulate baseline rates of operant responding.

Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism.

PubMed

Fan, Lu; Balakrishna, Shrilatha; Jabba, Sairam V; Bonner, Pamela E; Taylor, Seth R; Picciotto, Marina R; Jordt, Sven-Eric

2016-11-01

Nicotine is a major oral irritant in smokeless tobacco products and has an aversive taste. Mentholated smokeless tobacco products are highly popular, suggesting that menthol increases their palatability and may facilitate initiation of product use. While menthol is known to reduce respiratory irritation by tobacco smoke irritants, it is not known whether this activity extends to oral nicotine and its aversive effects. The two-bottle choice drinking assay was used to characterise aversion and preference in C57BL/6 mice to a range of menthol concentrations (10-200 µg/mL). Then, effects of menthol on oral nicotine aversion were determined. Responses were compared with those in mice deficient in the cold/menthol receptor, TRPM8, expressed in trigeminal sensory neurons innervating the oral cavity. Mice showed aversion to menthol concentrations of 100 µg/mL and above. When presented with a highly aversive concentration of nicotine (200 µg/mL), mice preferred solutions with 50 or 100 µg/mL menthol added over nicotine alone. In contrast to wild-type mice, Trpm8-/- showed a strong aversion to mentholated (100 µg/mL) nicotine (200 µg/mL) and preferred nicotine alone. Trpm8-/- mice show aversion to lower concentrations of menthol than wild-type mice. Oral menthol can reduce the aversive effects of oral nicotine and, at higher concentrations, acts as an irritant by itself. Menthol's effects in relation to nicotine require TRPM8, the cool temperature sensing ion channel that activates analgesic and counterirritant mechanisms. These mechanisms may underlie preference for menthol-containing smokeless tobacco products and may facilitate initiation of product use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Uptake of L-nicotine and of 6-hydroxy-L-nicotine by Arthrobacter nicotinovorans and by Escherichia coli is mediated by facilitated diffusion and not by passive diffusion or active transport.

PubMed

Ganas, Petra; Brandsch, Roderich

2009-06-01

The mechanism by which l-nicotine is taken up by bacteria that are able to grow on it is unknown. Nicotine degradation by Arthrobacter nicotinovorans, a Gram-positive soil bacterium, is linked to the presence of the catabolic megaplasmid pAO1. l-[(14)C]Nicotine uptake assays with A. nicotinovorans showed transport of nicotine across the cell membrane to be energy-independent and saturable with a K(m) of 6.2+/-0.1 microM and a V(max) of 0.70+/-0.08 micromol min(-1) (mg protein)(-1). This is in accord with a mechanism of facilitated diffusion, driven by the nicotine concentration gradient. Nicotine uptake was coupled to its intracellular degradation, and an A. nicotinovorans strain unable to degrade nicotine (pAO1(-)) showed no nicotine import. However, when the nicotine dehydrogenase genes were expressed in this strain, import of l-[(14)C]nicotine took place. A. nicotinovorans pAO1(-) and Escherichia coli were also unable to import 6-hydroxy-l-nicotine, but expression of the 6-hydroxy-l-nicotine oxidase gene allowed both bacteria to take up this compound. l-Nicotine uptake was inhibited by d-nicotine, 6-hydroxy-l-nicotine and 2-amino-l-nicotine, which may indicate transport of these nicotine derivatives by a common permease. Attempts to correlate nicotine uptake with pAO1 genes possessing similarity to amino acid transporters failed. In contrast to the situation at the blood-brain barrier, nicotine transport across the cell membrane by these bacteria was not by passive diffusion or active transport but by facilitated diffusion.

R-modafinil attenuates nicotine-taking and nicotine-seeking behavior in alcohol-preferring rats.

PubMed

Wang, Xiao-Fei; Bi, Guo-Hua; He, Yi; Yang, Hong-Ju; Gao, Jun-Tao; Okunola-Bakare, Oluyomi M; Slack, Rachel D; Gardner, Eliot L; Xi, Zheng-Xiong; Newman, Amy Hauck

2015-06-01

(±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long-Evans rats. As Long-Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long-Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans.

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

PubMed Central

Wang, Xiao-Fei; Bi, Guo-Hua; He, Yi; Yang, Hong-Ju; Gao, Jun-Tao; Okunola-Bakare, Oluyomi M; Slack, Rachel D; Gardner, Eliot L; Xi, Zheng-Xiong; Newman, Amy Hauck

2015-01-01

(±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long–Evans rats. As Long–Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long–Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans. PMID:25613829

Nicotine Transdermal Patch

MedlinePlus

... patches are used to help people stop smoking cigarettes. They provide a source of nicotine that reduces ... cause harm to the fetus.do not smoke cigarettes or use other nicotine products while using nicotine ...

Effect of Selective Inhibition of Reactivated Nicotine-Associated Memories With Propranolol on Nicotine Craving.

PubMed

Xue, Yan-Xue; Deng, Jia-Hui; Chen, Ya-Yun; Zhang, Li-Bo; Wu, Ping; Huang, Geng-Di; Luo, Yi-Xiao; Bao, Yan-Ping; Wang, Yu-Mei; Shaham, Yavin; Shi, Jie; Lu, Lin

2017-03-01

A relapse into nicotine addiction during abstinence often occurs after the reactivation of nicotine reward memories, either by acute exposure to nicotine (a smoking episode) or by smoking-associated conditioned stimuli (CS). Preclinical studies suggest that drug reward memories can undergo memory reconsolidation after being reactivated, during which they can be weakened or erased by pharmacological or behavioral manipulations. However, translational clinical studies using CS-induced memory retrieval-reconsolidation procedures to decrease drug craving reported inconsistent results. To develop and test an unconditioned stimulus (UCS)-induced retrieval-reconsolidation procedure to decrease nicotine craving among people who smoke. A translational rat study and human study in an academic outpatient medical center among 96 male smokers (aged 18- 45 years) to determine the association of propranolol administration within the time window of memory reconsolidation (after retrieval of the nicotine-associated memories by nicotine UCS exposure) with relapse to nicotine-conditioned place preference (CPP) and operant nicotine seeking in rats, and measures of preference to nicotine-associated CS and nicotine craving among people who smoke. The study rats were injected noncontingently with the UCS (nicotine 0.15 mg/kg, subcutaneous) in their home cage, and the human study participants administered a dose of propranolol (40 mg, per os; Zhongnuo Pharma). Nicotine CPP and operant nicotine seeking in rats, and preference and craving ratings for newly learned and preexisting real-life nicotine-associated CS among people who smoke. Sixty-nine male smokers completed the experiment and were included for statistical analysis: 24 in the group that received placebo plus 1 hour plus UCS, 23 who received propranolol plus 1 hour plus UCS, and 22 who received UCS plus 6 hours plus propranolol. In rat relapse models, propranolol injections administered immediately after nicotine UCS

Nicotine inhibits potassium currents in Aplysia bag cell neurons

PubMed Central

White, Sean H.; Sturgeon, Raymond M.

2016-01-01

Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPβS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K+ with Cs+. Consistent with an underlying mechanism of direct inhibition of one or more K+ channels, nicotine was found to rapidly reduce the fast-inactivating A-type K+ current as well as both components of the delayed-rectifier K+ current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K+ channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time. PMID:26864763

Nicotinic receptor involvement in antinociception induced by exposure to cigarette smoke.

PubMed

Simons, Christopher T; Cuellar, Jason M; Moore, Justin A; Pinkerton, Kent E; Uyeminami, Dale; Carstens, Mirela Iodi; Carstens, E

2005-12-02

Direct exposure of rats to tobacco smoke induces antinociception. We presently investigated if this antinociception is mediated via nicotinic and/or mu-opioid receptors. Adult male rats were surgically implanted with Alzet osmotic minipumps that delivered either saline (control), the nicotinic antagonist mecamylamine, or the opiate antagonist naltrexone (3 mg/kg/day i.v. for 21 days). Nocifensive responses were assessed on alternate days using tail-flick reflex latency (TFL) over a 3-week period. During the second week, the rats were exposed to concentrated cigarette smoke in an environmental chamber for 6 h/day for 5 consecutive days; a control group was similarly exposed to filtered cigarette smoke. Rats receiving mecamylamine and naltrexone exhibited a significant weight loss after the first day of infusion. All treatment groups additionally exhibited significant weight loss during exposure to unfiltered or filtered smoke. The saline group exhibited significant antinociception on the first day of smoke exposure with rapid development of tolerance. The mecamylamine and naltrexone groups did not exhibit significant antinociception. Controls exposed to filtered smoke (with approximately 50% lower nicotine concentration) also exhibited significant analgesia on the first exposure day with rapid development of tolerance. Exposure to high levels of cigarette smoke, or to filtered smoke with a lower nicotine concentration in the vapor phase, induces antinociception with rapid development of tolerance. The antinociceptive effect appears to be mediated via nicotinic and mu-opioid receptors.

Effects of chronic inhalation of electronic cigarettes containing nicotine on glial glutamate transporters and α-7 nicotinic acetylcholine receptor in female CD-1 mice.

PubMed

Alasmari, Fawaz; Crotty Alexander, Laura E; Nelson, Jessica A; Schiefer, Isaac T; Breen, Ellen; Drummond, Christopher A; Sari, Youssef

2017-07-03

Alteration in glutamate neurotransmission has been found to mediate the development of drug dependence, including nicotine. We and others, through using western blotting, have reported that exposure to drugs of abuse reduced the expression of glutamate transporter-1 (GLT-1) as well as cystine/glutamate antiporter (xCT), which consequently increased extracellular glutamate concentrations in the mesocorticolimbic area. However, our previous studies did not reveal any changes in glutamate/aspartate transporter (GLAST) following exposure to drugs of abuse. In the present study, for the first time, we investigated the effect of chronic exposure to electronic (e)-cigarette vapor containing nicotine, for one hour daily for six months, on GLT-1, xCT, and GLAST expression in frontal cortex (FC), striatum (STR), and hippocampus (HIP) in outbred female CD1 mice. In this study, we also investigated the expression of alpha-7 nicotinic acetylcholine receptor (α-7 nAChR), a major pre-synaptic nicotinic receptor in the glutamatergic neurons, which regulates glutamate release. We found that inhalation of e-cigarette vapor for six months increased α-7 nAChR expression in both FC and STR, but not in the HIP. In addition, chronic e-cigarette exposure reduced GLT-1 expression only in STR. Moreover, e-cigarette vapor inhalation induced downregulation of xCT in both the STR and HIP. We did not find any significant changes in GLAST expression in any brain region. Finally, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques, we detected high concentrations of nicotine and cotinine, a major metabolite of nicotine, in the FC tissues of e-cigarette exposed mice. These data provide novel evidence about the effects of chronic nicotine inhalation on the expression of key glial glutamate transporters as well as α-7 nAChR. Our work may suggest that nicotine exposure via chronic inhalation of e-cigarette vapor may be mediated in part by alterations in the glutamatergic

Fractal Analysis of Air Pollutant Concentrations

NASA Astrophysics Data System (ADS)

Cortina-Januchs, M. G.; Barrón-Adame, J. M.; Vega-Corona, A.; Andina, D.

2010-05-01

Air pollution poses significant threats to human health and the environment throughout the developed and developing countries. This work focuses on fractal analysis of pollutant concentration in Salamanca, Mexico. The city of Salamanca has been catalogued as one of the most polluted cities in Mexico. The main causes of pollution in this city are fixed emission sources, such as chemical industry and electricity generation. Sulphur Dioxide (SO2) and Particulate Matter less than 10 micrometer in diameter (PM10) are the most important pollutants in this region. Air pollutant concentrations were investigated by applying the box counting method in time series obtained of the Automatic Environmental Monitoring Network (AEMN). One year of time series of hourly average concentrations were analyzed in order to characterize the temporal structures of SO2 and PM10.

A nicotine delivery device without the nicotine? Tobacco industry development of low nicotine cigarettes.

PubMed

Dunsby, J; Bero, L

2004-12-01

Defining harm reduction and regulating potentially reduced exposure products (PREPs), including low nicotine products, are key issues in tobacco control policy. The US Congress has been considering legislation authorising the Food and Drug Administration (FDA) to regulate tobacco products. To investigate tobacco industry perceptions, interests, motivations, and knowledge regarding the marketability of low nicotine tobacco products. Qualitative analysis of internal tobacco industry documents identified in the Legacy Tobacco Documents Library between February 2002 and June 2004. Search terms included low-, no-, reduced-nicotine; denicotinization; low-, reduced- alkaloids; Next; de-nic; and key names of people, organisations, projects, and their common abbreviations and acronyms. The tobacco industry has made repeated efforts to develop low nicotine cigarettes. Reasons for doing so include consumer appeal and economic importance in a highly competitive cigarette market for "healthier" products. The industry considered the development of a new "denic" market segment a critical challenge. The tobacco industry exploits consumer misunderstanding of the health effects of nicotine in development and marketing efforts. The industry has risked the development of a less addictive product to expand the market reach of tobacco products based on perceived health benefits and appeal to quitters.

Oral fluid nicotine markers to assess smoking status and recency of use

PubMed Central

Scheidweiler, Karl B.; Marrone, Gina F.; Shakleya, Diaa M.; Singleton, Edward G.; Heishman, Stephen J.; Huestis, Marilyn A.

2011-01-01

Oral fluid collection is non-invasive and easily observed making it an attractive matrix for objectively determining smoking status. Despite large inter-subject variability, cotinine oral fluid concentrations correlate with cigarettes smoked per day (CPD). Few studies, however, assessed nicotine markers in oral fluid other than cotinine; other markers might improve smoking status assessment and/or time of last cigarette. Materials and Methods Smoking histories and oral fluid specimens were collected from non-treatment-seeking light (1–10 CPD) and heavy smokers (>10 CPD), and from environmentally exposed and nonexposed nonsmokers who provided written informed consent for this Institutional Review Board-approved study. Nicotine, cotinine, hydroxycotinine (OH-cotinine) and norcotinine oral fluid concentrations were quantified via liquid chromatography tandem mass spectrometry (LCMSMS). Results Comparison of 1, 3 and 10ng/mL oral fluid LCMSMS cutoffs demonstrated that 10ng/mL cutoffs performed optimally for cotinine, OH-cotinine, nicotine and norcotinine identifying 98, 97, 88 and 15% of self-reported smokers; 1% nonsmokers had >10ng/mL cotinine. No self-reported nonsmoker had >10ng/mL OH-cotinine, nicotine or norcotinine. Norcotinine was only identified in smokers’ oral fluid. Oral fluid nicotine, cotinine and nicotine/cotinine ratios were negatively correlated with time of last smoking (r=−0.53, −0.23, and −0.51; p<0.05) and CPD (r=0.35, 0.26 and 0.33; p<0.01), respectively. Discussion and Conclusion OH-cotinine performed slightly better than cotinine for distinguishing smokers from nonsmokers and should be considered as an additional oral fluid smoking indicator. Further research is required to determine if oral fluid norcotinine is a marker for distinguishing light and heavy smokers. Moderate correlations suggest nicotine, cotinine and nicotine/cotinine ratios may be useful for determining smoking recency in “spot samples” collected during nicotine

[Effects of nicotine on bone marrow stromal cells proliferation and differentiation of chondrocyte in vitro].

PubMed

Ying, Xiao-zhou; Peng, Lei; Cheng, Shao-wen; Chen, Qing-yu; Zhang, Wei; Kou, Dong-quan; Shen, Yue

2011-11-01

To examine the effects of various concentration of nicotine on bone marrow stromal cells (BMSCs) proliferation and differentiation of cartilaginous in vitro. BMSCs was obtained from femoral bone and tibia of New-Zealand albino rabbit. The cells of the 3rd generation were used in study. Different concentration of nicotine (0, 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) M) were added into BMSCs. BMSCs proliferation was analyzed by MTT assay at the 1, 4, 7, 14 days. The expression of collagen type II and aggrecan as the marker genes of cartilaginous differentiation from BMSCs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Microscope showed that BMSCs transformed from round to fusiform shape. The concentration of nicotine in 1 x 10(-7), 1 x 10(-6) M had a significant positive effect on cell proliferation and the expression of type II collagen in a time-dependent manner when supplemented in commonly used induction media (P<0.05). Concentrations of nicotine in 1 x 10(-7) can promote the expression of aggrecan at the 7th day after induction,and in 1 x 10(-5) M may inhibit the expression of type II collagen and aggrecan. It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing cartilaginous differentiation capacity of BMSCs in cartilage tissue engineering.

Novel nicotine analogues with potential anti-mycobacterial activity.

PubMed

Gandhi, Paresh T; Athmaram, Thimmasandra Narayanappa; Arunkumar, Gundaiah Ramesh

2016-04-15

Tuberculosis (TB) is the second leading lethal infectious disease in the world after acquired immuno deficiency (AIDs). We have developed a series of twenty-five novel nicotine analogues with de-addiction property and tested them for their activity against Mycobacterium tuberculosis (MTB). In an effort to increase the specificity of action and directing nicotine analogues to target MTB, four promising compounds were further optimized via molecular docking studies against the Dihydrofolate reductase of MTB. After lead optimization, one nicotine analogue [3-(5-(3fluorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one] exhibited minimum inhibitory concentration of 1 μg/mL (2.86 nM) against M. tuberculosis (H37Rv strain), a human pathogenic strain of clinically significant importance. Pharmacokinetic analysis of [3-(5-(3fluorophenyl)nicotinoyl)-1methylpyrrolidin-2-one] with lowest MIC value via oral route in Wistar rats revealed that at a dosage of 5 mg/kg body weight gave a maximum serum drug concentration (Cmax) of 2.86 μg/mL, Tmax of one hour and a half-life (T1/2) of more than 24 h and Volume of distribution (Vd) of 27.36 L. Whereas the parenteral (intra venous) route showed a Cmax of 3.37 μg/mL, Tmax of 0.05 h, T1/2 of 24 h and Vd equivalent to 23.18 L. The acute oral toxicity and repeated oral toxicity studies in female Wistar rats had an LD50>2000 mg/kg body weight. Our data suggests that nicotine derivatives developed in the present study has good metabolic stability with tunable pharmacokinetics (PK) with therapeutic potential to combat MTB. However, further in vivo studies for anti-tuberculosis activity and elucidation of mode of action could result in more promising novel drug for treating MTB. To the best of our knowledge this is the first report revealing the anti-mycobacterial potential of nicotine analogue at potential therapeutic concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.

PubMed

Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer; Stadler, Ashley; Levin, Edward D; Seidler, Frederic J

2015-09-01

Tobacco smoke contains thousands of compounds in addition to nicotine, a known neuroteratogen. We evaluated the developmental neurotoxicity of tobacco smoke extract (TSE) administered to pregnant rats starting preconception and continued through the second postnatal week. We simulated nicotine concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers, and compared TSE with an equivalent dose of nicotine alone, and to a 10-fold higher nicotine dose. We conducted longitudinal evaluations in multiple brain regions, starting in adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although both nicotine doses produced presynaptic cholinergic deficits, these were partially compensated by hyperinnervation and receptor upregulation, effects that were absent with TSE. TSE also produced deficits in serotonin receptors in females that were not seen with nicotine. Regression analysis showed a profound sex difference in the degree to which nicotine could account for overall TSE effects: whereas the 2 nicotine doses accounted for 36%-46% of TSE effects in males, it accounted for only 7%-13% in females. Our results show that the adverse effects of TSE on neurodevelopment exceed those that can be attributed to just the nicotine present in the mixture, and further, that the sensitivity extends down to levels commensurate with second-hand smoke exposure. Because nicotine itself evoked deficits at low exposures, "harm reduction" nicotine products do not eliminate the potential for neurodevelopmental damage. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology.All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Surveillance of Nicotine and pH in Cigarette and Cigar Filler

PubMed Central

Lawler, Tameka S.; Stanfill, Stephen B.; deCastro, B. Rey; Lisko, Joseph G.; Duncan, Bryce W.; Richter, Patricia; Watson, Clifford H.

2017-01-01

Objective We examined differences between nicotine concentrations and pH in cigarette and cigar tobacco filler. Methods Nicotine and pH levels for 50 cigarette and 75 cigar brands were measured. Non-mentholated and mentholated cigarette products were included in the analysis along with several cigar types as identified by the manufacturer: large cigars, pipe tobacco cigars, cigarillos, mini cigarillos, and little cigars. Results There were significant differences found between pH and nicotine for cigarette and cigar tobacco products. Mean nicotine concentrations in cigarettes (19.2 mg/g) and large cigars (15.4 mg/g) were higher than the other cigars types, especially the pipe tobacco cigars (8.79 mg/g). The mean pH for cigarettes was pH 5.46. Large cigars had the highest mean pH value (pH 6.10) and pipe tobacco cigars had the lowest (pH 5.05). Conclusions Although cigarettes are the most common combustible tobacco product used worldwide, cigar use remains popular. Our research provides a means to investigate the possibility of distinguishing the 2 tobacco product types and offers information on nicotine and pH across a wide range of cigarette and cigar varieties that may be beneficial to help establish tobacco policies and regulations across product types. PMID:28989950

Validation of a LC-MS/MS Method for Quantifying Urinary Nicotine, Six Nicotine Metabolites and the Minor Tobacco Alkaloids—Anatabine and Anabasine—in Smokers' Urine

PubMed Central

McGuffey, James E.; Wei, Binnian; Bernert, John T.; Morrow, John C.; Xia, Baoyun; Wang, Lanqing; Blount, Benjamin C.

2014-01-01

Tobacco use is a major contributor to premature morbidity and mortality. The measurement of nicotine and its metabolites in urine is a valuable tool for evaluating nicotine exposure and for nicotine metabolic profiling—i.e., metabolite ratios. In addition, the minor tobacco alkaloids—anabasine and anatabine—can be useful for monitoring compliance in smoking cessation programs that use nicotine replacement therapy. Because of an increasing demand for the measurement of urinary nicotine metabolites, we developed a rapid, low-cost method that uses isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously quantifying nicotine, six nicotine metabolites, and two minor tobacco alkaloids in smokers' urine. This method enzymatically hydrolyzes conjugated nicotine (primarily glucuronides) and its metabolites. We then use acetone pretreatment to precipitate matrix components (endogenous proteins, salts, phospholipids, and exogenous enzyme) that may interfere with LC-MS/MS analysis. Subsequently, analytes (nicotine, cotinine, hydroxycotinine, norcotinine, nornicotine, cotinine N-oxide, nicotine 1′-N-oxide, anatabine, and anabasine) are chromatographically resolved within a cycle time of 13.5 minutes. The optimized assay produces linear responses across the analyte concentrations typically found in urine collected from daily smokers. Because matrix ion suppression may influence accuracy, we include a discussion of conventions employed in this procedure to minimize matrix interferences. Simplicity, low cost, low maintenance combined with high mean metabolite recovery (76–99%), specificity, accuracy (0–10% bias) and reproducibility (2–9% C.V.) make this method ideal for large high through-put studies. PMID:25013964

Nicotine poisoning

MedlinePlus

... gets medical help, the better the chance for recovery. A nicotine overdose may cause seizures or death. However, unless there are complications, long-term effects from nicotine overdose are uncommon.

Oxytocin attenuates aversive response to nicotine and anxiety-like behavior in adolescent rats.

PubMed

Lee, Hyunchan; Jang, Minji; Noh, Jihyun

2017-02-01

Initial tobacco use is initiated with rewarding and aversive properties of nicotine and aversive response to nicotine plays a critical role in nicotine dependency. Decrease of nicotine aversion increases the nicotine use that causes behavioral and neuronal changes of animals. Oxytocin influences drug abuse and reciprocally affect vulnerability to drug use. To assess the effect of oxytocin on initial nicotine aversion and anxiety, we examined voluntary oral nicotine intake and anxiety-like behavior following oxytocin treatment in adolescent rats. Sprague-Dawley male rats (4 weeks old) were used. For oxytocin administration, rats were injected subcutaneously with saline or oxytocin (0.01, 0.1 and 1mg/kg) according to the assigned groups. Voluntary oral nicotine consumption test was performed by two bottle free-choice paradigm. To examine anxiety-like behavior in rats, we performed a light/dark box test. Oxytocin not only significantly increased the nicotine intake but also alleviated nicotine aversion after acclimation to nicotine solution in a concentration dependent manner. Meanwhile, oxytocin significantly reduced anxiety-like behavior. We suggest that oxytocin itself mitigates aversive response toward initial nicotine intake and anxiety-like behavior. These results widen the psychophysiological perspective on oxytocin for better understanding of nicotine addiction related behaviors influenced by diverse social factors. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Effects of 1,8-cineole on hypertension induced by chronic exposure to nicotine in rats.

PubMed

Moon, Hea Kyung; Kang, Purum; Lee, Hui Su; Min, Sun Seek; Seol, Geun Hee

2014-05-01

The monoterpenic oxide 1,8-cineole is a major component of many essential oils. We investigated its effects on systolic blood pressure (SBP) and oxidative stress in rats chronically exposed to nicotine. Male Sprague-Dawley rats (100-120 g) were intraperitoneally injected with 0.8 mg/kg/day nicotine for 21 days, followed by 3 mg/kg nicotine the next day. Rats were subsequently injected intraperitoneally with 0.01, 0.1 and 1 mg/kg 1,8-cineole, or 10 mg/kg nifedipine. SBP was measured using a tail cuff transducer, plasma nitrite concentration was measured colorimetrically, and plasma corticosterone concentration was measured by enzyme immunoassay. We found that 0.1 mg/kg 1,8-cineole significantly reduced SBP, and that 1.0 mg/kg 1,8-cineole significantly increased plasma nitrite concentrations, compared with rats chronically exposed to nicotine alone. Rats chronically exposed to nicotine showed a significant increase in lipid peroxidation levels, an elevation significantly antagonized by treatment with 0.01 mg/kg and 0.1 mg/kg 1,8-cineole. Chronic exposure to nicotine also significantly increased plasma corticosterone levels, but this effect was not diminished by treatment with 1,8-cineole. These results indicate that 1,8-cineole may lower blood pressure, and that this antihypertensive effect may be associated with the regulation of nitric oxide and oxidative stress in rats chronically exposed to nicotine. © 2013 Royal Pharmaceutical Society.

Differential discriminative-stimulus effects of cigarette smoke condensate and nicotine in nicotine-discriminating rats.

PubMed

Lee, Jun-Yeob; Choi, Mee Jung; Choe, Eun Sang; Lee, Young-Ju; Seo, Joung-Wook; Yoon, Seong Shoon

2016-06-01

Although it is widely accepted that nicotine plays a key role in tobacco dependence, nicotine alone cannot account for all of the pharmacological effects associated with cigarette smoke found in preclinical models. Thus, the present study aimed to determine the differential effects of the interoceptive cues of nicotine alone versus those of cigarette smoke condensate (CSC) in nicotine-trained rats. First, the rats were trained to discriminate nicotine (0.4mg/kg, subcutaneous [s.c.]) from saline in a two-lever drug discrimination paradigm. Then, to clarify the different neuropharmacological mechanisms underlying the discriminative-stimulus effects in the nicotine and CSC in nicotine-trained rats, either the α4β2 nicotinic acetylcholine receptor (nAChR) antagonist dihydro-β-erythroidine (DHβE; 0.3-1.0mg/kg, s.c.) or the α7 nAChR antagonist methyllycaconitine citrate (MLA; 5-10mg/kg, intraperitoneal [i.p.]) was administered prior to the injection of either nicotine or CSC. Separate set of experiments was performed to compare the duration of action of the discriminative-stimulus effects of CSC and nicotine. CSC exhibited a dose-dependent nicotine generalization, and interestingly, 1.0mg/kg of DHβE antagonized the discriminative effects of nicotine (0.4mg/kg) but not CSC (0.4mg/kg nicotine content). However, pretreatment with MLA had no effect. In the time-course study, CSC had a relatively longer half-life in terms of the discriminative-stimulus effects compared with nicotine alone. Taken together, the present findings indicate that CSC has a distinct influence on interoceptive effects relative to nicotine alone and that these differential effects might be mediated, at least in part, by the α4β2, but not the α7, nAChR. Copyright © 2016 Elsevier B.V. All rights reserved.

Meconium Nicotine and Metabolites by Liquid Chromatography–Tandem Mass Spectrometry: Differentiation of Passive and Nonexposure and Correlation with Neonatal Outcome Measures

PubMed Central

Gray, Teresa R.; Magri, Raquel; Shakleya, Diaa M.; Huestis, Marilyn A.

2011-01-01

BACKGROUND Meconium analysis is a diagnostically sensitive and objective alternative to maternal self-report for detecting prenatal tobacco exposure. Nicotine and metabolite disposition in meconium is poorly characterized, and correlation of analytes’ concentrations with neonatal outcomes is unexplored. Our objectives were to quantify nicotine, cotinine, trans-3′-hydroxycotinine (OH-cotinine), nornicotine, norcotinine, and glucuronide concentrations in meconium, identify the best biomarkers of in utero tobacco exposure, compare meconium concentrations of tobacco-exposed and nonexposed neonates, and investigate concentration–outcome relationships. METHODS We quantified concentrations of nicotine and 4 metabolites with and without hydrolysis simultaneously in meconium from tobacco-exposed and nonexposed neonates by liquid chromatography–tandem mass spectrometry. We compared meconium concentrations to birth weight, length, head circumference, gestational age, and 1- and 5-min Apgar scores. RESULTS Nicotine, cotinine, and OH-cotinine were the most prevalent and abundant meconium tobacco biomarkers and were found in higher concentrations in tobacco-exposed neonates. Whereas cotinine and OH-cotinine are glucuronide bound, performing the lengthy and costly enzymatic hydrolysis identified only 1 additional positive specimen. Unconjugated nicotine, cotinine, or OH-cotinine meconium concentration >10 ng/g most accurately discriminated active from passive and nonexposed neonates. There was no significant correlation between quantitative nicotine and metabolite meconium results and neonatal outcomes, although presence of a nicotine biomarker predicted decreased head circumference. CONCLUSIONS Unconjugated nicotine, cotinine, and OH-cotinine should be analyzed in meconium to detect in utero tobacco exposure, as approximately 25% of positive specimens did not contain cotinine. Immunoassay testing monitoring cotinine only would underestimate the prevalence of prenatal

Concentrations of selected contaminants in cabin air of airbus aircrafts.

PubMed

Dechow, M; Sohn, H; Steinhanses, J

1997-07-01

The concentrations of selected air quality parameters in aircraft cabins were investigated including particle numbers in cabin air compared to fresh air and recirculation air, the microbiological contamination and the concentration of volatile organic compounds (VOC). The Airbus types A310 of Swissair and A340 of Lufthansa were used for measurements. The particles were found to be mainly emitted by the passengers, especially by smokers. Depending on recirculation filter efficiency the recirculation air contained a lower or equal amount of particles compared to the fresh air, whereas the amount of bacteria exceeded reported concentrations within other indoor spaces. The detected species were mainly non-pathogenic, with droplet infection over short distances identified as the only health risk. The concentration of volatile organic compounds (VOC) were well below threshold values. Ethanol was identified as the compound with the highest amount in cabin air. Further organics were emitted by the passengers--as metabolic products or by smoking--and on ground as engine exhaust (bad airport air quality). Cleaning agents may be the source of further compounds.

Decreased nicotinic receptor availability in smokers with slow rates of nicotine metabolism

PubMed Central

Dubroff, Jacob G.; Doot, Robert K.; Falcone, Mary; R, Robert A. Schnoll; Ray, Riju; Tyndale, Rachel F.; Brody, Arthur L.; Hou, Catherine; Schmitz, Alexander; Lerman, Caryn

2015-01-01

The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR availability (α4β2* subtype) using positron emission tomography (PET) imaging of the radiotracer 2-18F-FA-85380 (2-18F-FA). Methods Twenty four smokers, 12 slow metabolizers (NMR <0.26) and 12 normal metabolizers (NMR ≥0.26), underwent 2-18F-FA-PET brain imaging following overnight nicotine abstinence (18 hours prior to scanning), using a validated bolus plus infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest (VOIs), with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed prior to and following the scans. Results Thalamic nAChR α4β2* availability was significantly reduced in slow (versus normal) nicotine metabolizers (P=0.04). Slow metabolizers exhibited greater reductions in craving than normal metabolizers from pre- to post-scanning; however, craving was unrelated to availability. Conclusion The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies differences in treatment response between slow and normal metabolizers of nicotine. PMID:26272810

Nicotine absorption from electronic cigarette use: comparison between first and new-generation devices.

PubMed

Farsalinos, Konstantinos E; Spyrou, Alketa; Tsimopoulou, Kalliroi; Stefopoulos, Christos; Romagna, Giorgio; Voudris, Vassilis

2014-02-26

A wide range of electronic cigarette (EC) devices, from small cigarette-like (first-generation) to new-generation high-capacity batteries with electronic circuits that provide high energy to a refillable atomizer, are available for smokers to substitute smoking. Nicotine delivery to the bloodstream is important in determining the addictiveness of ECs, but also their efficacy as smoking substitutes. In this study, plasma nicotine levels were measured in experienced users using a first- vs. new-generation EC device for 1 hour with an 18 mg/ml nicotine-containing liquid. Plasma nicotine levels were higher by 35-72% when using the new- compared to the first-generation device. Compared to smoking one tobacco cigarette, the EC devices and liquid used in this study delivered one-third to one-fourth the amount of nicotine after 5 minutes of use. New-generation EC devices were more efficient in nicotine delivery, but still delivered nicotine much slower compared to tobacco cigarettes. The use of 18 mg/ml nicotine-concentration liquid probably compromises ECs' effectiveness as smoking substitutes; this study supports the need for higher levels of nicotine-containing liquids (approximately 50 mg/ml) in order to deliver nicotine more effectively and approach the nicotine-delivery profile of tobacco cigarettes.

T-type calcium channel antagonism decreases motivation for nicotine and blocks nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine.

PubMed

Uslaner, Jason M; Vardigan, Joshua D; Drott, Jason M; Uebele, Victor N; Renger, John J; Lee, Ariel; Li, Zhaoxia; Lê, A D; Hutson, Pete H

2010-10-15

Recent evidence suggests an involvement of T-type calcium channels in the effects of drugs of abuse. We examined the influence of the novel, potent, and selective T-type calcium channel antagonist [2-(4-cyclopropylphenyl)-N-((1R)-1-{5-[2,2,2-trifluoroethyl]oxo}pyridine-2-yl)ethyl]acetamide] (TTA-A2) (.3, 1, or 3 mg/kg) on motivation for nicotine, as measured by nicotine self-administration on a progressive ratio (PR) schedule, and nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine delivery (n = 11 or 12 Long Evans rats/group). Furthermore, we examined the specificity of the TTA-A2 effects by characterizing its influence on PR responding for food (in the absence or presence of nicotine-potentiated responding), food- versus nicotine-induced cue-potentiated reinstatement for a response previously reinforced by food administration (n = 11 or 12 Wistar Hannover rats/group), and its ability to induce a conditioned place aversion. TTA-A2 dose-dependently decreased self-administration of nicotine on a PR schedule and the ability of both nicotine and a cue paired with nicotine to reinstate responding. The effects were specific for nicotine's incentive motivational properties, as TTA-A2 did not influence responding for food on a PR schedule but did attenuate the ability of nicotine to potentiate responding for food. Likewise, TTA-A2 did not alter food-induced cue-potentiated reinstatement for a response previously reinforced by food but did decrease nicotine-induced cue-potentiated reinstatement. Finally, TTA-A2 did not produce an aversive state, as indicated by a lack of ability to induce conditioned place aversion. These data suggest that T-type calcium channel antagonists have potential for alleviating nicotine addiction by selectively decreasing the incentive motivational properties of nicotine. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Prenatal cigarette smoke exposure: Pregnancy outcome and gestational changes in plasma nicotine concentration, hematocrit, and carboxyhemoglobin in a newly standardized rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farkas, Svetlana; Hussein, Jabeen; Ariano, Robert E.

Epidemiological studies support an association between perinatal cigarette smoke (CS) exposure and a number of severe pre- and postnatal complications. However, the mechanisms through which CS enhances such risks largely remain unknown. One of the reasons for our inability to discover such mechanisms has been the unavailability of a clinically relevant and physiologically concordant animal model. A number of studies have previously used nicotine (Nic) as surrogate for CS. We sought to (1) establish the amount of CS exposure to achieve plasma Nic concentrations observed among moderate to heavy smokers (20-60 ng/ml) (2) investigate the temporal changes in plasma Nicmore » concentrations, carboxyhemoglobin, and hematocrit with advancing pregnancy, and (3) elucidate the effects of CS exposure on pregnancy outcome. Pregnant Sprague-Dawley rats were exposed to various doses of CS or room air (Sham) from days 6 to 21 of gestation. Exposure to 6000 ml/day of CS led to very high plasma Nic concentrations and increased maternal and fetal mortality (P < 0.001). The plasma Nic concentrations remained higher than those observed in moderate smokers until the CS dose was reduced to 1000 ml/day and showed dose-dependent temporal changes with advancing gestational age. Significant increases in carboxyhemoglobin and hematocrit were observed in the CS group as compared with the Sham group (P < 0.001). In addition, prenatally CS exposed fetuses had lower birth weight as compared with the Sham group (P = 0.04). Our current study establishes a newly standardized and physiologically relevant model to investigate the mechanisms of CS-mediated adverse effects during the critical period of fetal development.« less

The Influence of Puff Characteristics, Nicotine Dependence, and Rate of Nicotine Metabolism on Daily Nicotine Exposure in African American Smokers.

PubMed

Ross, Kathryn C; Dempsey, Delia A; St Helen, Gideon; Delucchi, Kevin; Benowitz, Neal L

2016-06-01

African American (AA) smokers experience greater tobacco-related disease burden than Whites, despite smoking fewer cigarettes per day (CPD). Understanding factors that influence daily nicotine intake in AA smokers is an important step toward decreasing tobacco-related health disparities. One factor of interest is smoking topography, or the study of puffing behavior. (i) to create a model using puff characteristics, nicotine dependence, and nicotine metabolism to predict daily nicotine exposure, and (ii) to compare puff characteristics and nicotine intake from two cigarettes smoked at different times to ensure the reliability of the puff characteristics included in our model. Sixty AA smokers smoked their preferred brand of cigarette at two time points through a topography device. Plasma nicotine, expired CO, and changes in subjective measures were measured before and after each cigarette. Total nicotine equivalents (TNE) was measured from 24-hour urine collected during ad libitum smoking. In a model predicting daily nicotine exposure, total puff volume, CPD, sex, and menthol status were significant predictors (R(2) = 0.44, P < 0.001). Total puff volume was significantly greater and inter-puff intervals were significantly shorter after ad lib smoking compared with the first cigarette of the day, but puffing behaviors for both cigarettes were highly correlated (r range = 0.69-0.89, P < 0.001) within-subjects. This is the first study, to our knowledge, to show that puff characteristics of individual cigarettes are predictive of daily nicotine intake. These findings enhance our understanding of the relationship between smoking behavior and nicotine intake in AA smokers. Cancer Epidemiol Biomarkers Prev; 25(6); 936-43. ©2016 AACR. ©2016 American Association for Cancer Research.

Effect of an ozone-generating air-purifying device on reducing concentrations of formaldehyde in air

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esswein, E.J.; Boeniger, M.F.

1994-02-01

Formaldehyde, an air contaminant found in many indoor air investigations, poses distinct occupational exposure hazards in certain job categories (e.g., mortuary science) but is also of concern when found or suspected in office buildings and homes. A variety of air-purifying devices (APDs) are currently available or marketed for application to reduce or remove concentrations of a variety of indoor air pollutants through the use of ozone as a chemical oxidant. An investigation was conducted to determine if concentrations of formaldehyde similar to those found in industrial hygiene evaluations of funeral homes could be reduced with the use of an ozone-generatingmore » APD. An ozone-generating APD was placed in an exposure chamber and formaldehyde-containing embalming solution was allowed to evaporate naturally, creating peak and mean chamber concentrations of 2.5 and 1.3 ppm, respectively. Continuous-reading instruments were used to sample for formaldehyde and ozone. Active sampling methods were also used to sample simultaneously for formaldehyde and a possible reactant product, formic acid. Triplicate measurements were made in each of three evaluations: formaldehyde alone, ozone alone, and formaldehyde and ozone combined. Concentrations of formaldehyde were virtually identical with and without 0.5 ppm ozone. No reduction in formaldehyde concentration was found during a 90-minute evaluation using ozone at this concentration with peak and average concentrations of approximately 2.5 and 1.3 ppm formaldehyde, respectively. The results of this investigation suggest that the use of ozone is ineffective in reducing concentrations of formaldehyde. Because ozone has demonstrated health hazards, and is a regulated air contaminant in both the occupational and ambient environment, the use of ozone as an air purification agent in indoor air does not seem warranted. 25 refs., 5 figs., 4 tabs.« less

Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

PubMed

Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

2015-07-15

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

Constituents of smoke from cigarettes made from diverted nicotine replacement therapy patches.

PubMed

Morrissey, Hana; Ball, Patrick; Boland, Martin; Hefler, Marita; Thomas, David P

2016-03-01

Anecdotes of nicotine replacement therapy patch misuse associated with the introduction of smoke-free prisons have been reported by media internationally, including Canada in 2006, New Zealand in 2011 and Australia in 2014. This study identifies chemical compounds released through diverted nicotine replacement therapy patches when they are smoked. Two samples were produced: (i) shredded 21 mg nicotine replacement therapy patches rolled with tea leaves into a cigarette; and (ii) patches boiled in water and tea leaves, and then dried tea leaves rolled into a cigarette. The smoke was tested for nicotine, caffeine and toxins. High-performance liquid chromatography, mass spectrometry and spectrophotometry were used to detect the presence and quantity of nicotine and caffeine. A specialised laboratory was contracted to test the presence of toxins. Nicotine was liberated when the two samples were burnt but not if the nicotine replacement therapy patches were boiled in water alone. High concentrations of formaldehyde, acetaldehyde, acrolein, toluene, xylene and heavy metals were also released. Nicotine is released when diverted nicotine replacement therapy patches are smoked, as are caffeine and harmful toxins. These toxins have the potential to cause short- and long-term health damage. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Influence of air humidity and the distance from the source on negative air ion concentration in indoor air.

PubMed

Wu, Chih Cheng; Lee, Grace W M; Yang, Shinhao; Yu, Kuo-Pin; Lou, Chia Ling

2006-10-15

Although negative air ionizer is commonly used for indoor air cleaning, few studies examine the concentration gradient of negative air ion (NAI) in indoor environments. This study investigated the concentration gradient of NAI at various relative humidities and distances form the source in indoor air. The NAI was generated by single-electrode negative electric discharge; the discharge was kept at dark discharge and 30.0 kV. The NAI concentrations were measured at various distances (10-900 cm) from the discharge electrode in order to identify the distribution of NAI in an indoor environment. The profile of NAI concentration was monitored at different relative humidities (38.1-73.6% RH) and room temperatures (25.2+/-1.4 degrees C). Experimental results indicate that the influence of relative humidity on the concentration gradient of NAI was complicated. There were four trends for the relationship between NAI concentration and relative humidity at different distances from the discharge electrode. The changes of NAI concentration with an increase in relative humidity at different distances were quite steady (10-30 cm), strongly declining (70-360 cm), approaching stability (420-450 cm) and moderately increasing (560-900 cm). Additionally, the regression analysis of NAI concentrations and distances from the discharge electrode indicated a logarithmic linear (log-linear) relationship; the distance of log-linear tendency (lambda) decreased with an increase in relative humidity such that the log-linear distance of 38.1% RH was 2.9 times that of 73.6% RH. Moreover, an empirical curve fit based on this study for the concentration gradient of NAI generated by negative electric discharge in indoor air was developed for estimating the NAI concentration at different relative humidities and distances from the source of electric discharge.

Review. Neurobiology of nicotine dependence.

PubMed

Markou, Athina

2008-10-12

Nicotine is a psychoactive ingredient in tobacco that significantly contributes to the harmful tobacco smoking habit. Nicotine dependence is more prevalent than dependence on any other substance. Preclinical research in animal models of the various aspects of nicotine dependence suggests a critical role of glutamate, gamma-aminobutyric acid (GABA), cholinergic and dopamine neurotransmitter interactions in the ventral tegmental area and possibly other brain sites, such as the central nucleus of the amygdala and the prefrontal cortex, in the effects of nicotine. Specifically, decreasing glutamate transmission or increasing GABA transmission with pharmacological manipulations decreased the rewarding effects of nicotine and cue-induced reinstatement of nicotine seeking. Furthermore, early nicotine withdrawal is characterized by decreased function of presynaptic inhibitory metabotropic glutamate 2/3 receptors and increased expression of postsynaptic glutamate receptor subunits in limbic and frontal brain sites, while protracted abstinence may be associated with increased glutamate response to stimuli associated with nicotine administration. Finally, adaptations in nicotinic acetylcholine receptor function are also involved in nicotine dependence. These neuroadaptations probably develop to counteract the decreased glutamate and cholinergic transmission that is hypothesized to characterize early nicotine withdrawal. In conclusion, glutamate, GABA and cholinergic transmission in limbic and frontal brain sites are critically involved in nicotine dependence.

U.S. adults' addiction and harm beliefs about nicotine and low nicotine cigarettes☆

PubMed Central

O'Brien, Erin Keely; Nguyen, Anh B.; Persoskie, Alexander; Hoffman, Allison C.

2017-01-01

This research described U.S. adults' beliefs about nicotine and low nicotine cigarettes (LNCs) using the nationally-representative Health Information National Trends Survey (HINTS-FDA 2015; N = 3738). About three quarters of people either were unsure of the relationship between nicotine and cancer or incorrectly believed that nicotine causes cancer. People who were non-White, less educated, age 65+, and never established smokers were most likely to be unaware that nicotine is not a cause of cancer. More than a quarter of people held the potentially inaccurate beliefs that LNCs would be less harmful and addictive than typical cigarettes. Whites were more likely than Blacks to believe LNCs were less harmful than typical cigarettes, and never smokers were more likely to believe this than established quitters. Whites and people with at least a college degree were more likely to believe that LNCs would be less addictive than typical cigarettes. Overall, we found that many people, particularly the demographic subgroups identified here, held incorrect beliefs about nicotine and potentially inaccurate beliefs about LNCs. Findings should be considered in assessing the public health impact of marketing low nicotine products. Incorrectly believing that nicotine causes cancer could discourage smokers from switching to safer nicotine-containing alternatives, and could lead nonsmokers to experiment with low nicotine tobacco products, believing that cancer risk would be reduced. Findings underscore the need to educate the public on the health effects of nicotine and LNCs, and can help public health practitioners determine which subgroups should be prioritized in targeted educational efforts. PMID:28034733

Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent nicotine+cocaine self-administration.

PubMed

Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

2014-04-01

Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at α4β2* and α6β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at α7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatta). Varenicline (0.004-0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7-10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding returned to baseline. During control treatment, nicotine+cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05-0.001). Varenicline dose-dependently reduced responding maintained by nicotine alone (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj) (P<0.05) with no significant effects on food-maintained responding. However, varenicline did not significantly decrease self-administration of a low dose of nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg cocaine combined with the same doses of nicotine. We conclude that varenicline selectively attenuates the reinforcing effects of nicotine alone but not cocaine alone, and its effects on nicotine+cocaine combinations are dependent on the dose of cocaine.

Effects of Chronic Varenicline Treatment on Nicotine, Cocaine, and Concurrent Nicotine+Cocaine Self-Administration

PubMed Central

Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

2014-01-01

Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at α4β2* and α6β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at α7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatta). Varenicline (0.004–0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7–10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding returned to baseline. During control treatment, nicotine+cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05–0.001). Varenicline dose-dependently reduced responding maintained by nicotine alone (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj) (P<0.05) with no significant effects on food-maintained responding. However, varenicline did not significantly decrease self-administration of a low dose of nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg cocaine combined with the same doses of nicotine. We conclude that varenicline selectively attenuates the reinforcing effects of nicotine alone but not cocaine alone, and its effects on nicotine+cocaine combinations are dependent on the dose of cocaine. PMID:24304823

Discriminative and Reinforcing Stimulus Effects of Nicotine, Cocaine, and Cocaine + Nicotine Combinations in Rhesus Monkeys

PubMed Central

Mello, Nancy K.; Newman, Jennifer L.

2011-01-01

Concurrent cigarette smoking and cocaine use is well documented. However, the behavioral pharmacology of cocaine and nicotine combinations is poorly understood, and there is a need for animal models to examine this form of polydrug abuse. The purpose of this study was two-fold: first to assess the effects of nicotine on the discriminative stimulus effects of cocaine, and second, to study self-administration of nicotine/cocaine combinations in a novel polydrug abuse model. In drug discrimination experiments, nicotine increased the discriminative stimulus effects of low cocaine doses in two of three monkeys, but nicotine did not substitute for cocaine in any monkey. Self-administration of cocaine and nicotine alone, and cocaine + nicotine combinations was studied under a second-order fixed ratio 2, variable ratio 16 (FR2[VR16:S]) schedule of reinforcement. Cocaine and nicotine alone were self-administered in a dose-dependent manner. The combination of marginally reinforcing doses of cocaine and nicotine increased drug self-administration behavior above levels observed with the same dose of either cocaine or nicotine alone. These findings indicate that nicotine may increase cocaine’s discriminative stimulus and reinforcing effects in rhesus monkeys, and illustrate the feasibility of combining cocaine and nicotine in a preclinical model of polydrug abuse. Further studies of the behavioral effects of nicotine + cocaine combinations will contribute to our understanding the pharmacology of dual nicotine and cocaine dependence, and will be useful for evaluation of new treatment medications. PMID:21480727

alpha 4 beta 2 subunit combination specific pharmacology of neuronal nicotinic acetylcholine receptors in N1E-115 neuroblastoma cells.

PubMed

Zwart, R; Abraham, D; Oortgiesen, M; Vijverberg, H P

1994-08-22

Pharmacological characteristics of native neuronal nicotinic acetylcholine receptor-mediated ion currents in mouse N1E-115 neuroblastoma cells have been investigated by superfusion of voltage clamped cells with known concentrations of the agonists acetylcholine, nicotine and cytisine, and the antagonists alpha-bungarotoxin and neuronal bungarotoxin. The sensitivity of the nicotinic acetylcholine receptor for agonists followed the agonist potency rank-order: nicotine approximately acetylcholine > cytisine. The EC50 values of acetylcholine and nicotine are 78 microM and 76 microM, respectively. Equal concentrations of acetylcholine and nicotine induce inward currents with approximately the same peak amplitude whereas cytisine induces much smaller inward currents. Acetylcholine-induced currents are unaffected by high concentrations of alpha-bungarotoxin. Conversely, at 10 and 90 nM neuronal bungarotoxin reduces the amplitude of the 1 mM acetylcholine-induced inward current to 47% and 11% of control values, respectively. Both the agonist potency rank-order and the differential sensitivity to snake toxins of nicotinic receptors in N1E-115 cells are consistent with the known pharmacological profile of alpha 4 beta 2 nicotinic receptors expressed in Xenopus oocytes and distinct from those of all other nicotinic acetylcholine receptors of known functional subunit compositions. All data indicate that the native nicotinic acetylcholine receptor in N1E-115 cells is an assembly of alpha 4 and beta 2 subunits, the putative major subtype of nicotinic acetylcholine receptor in the brain.

Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch.

PubMed

Linakis, Matthew W; Rower, Joseph E; Roberts, Jessica K; Miller, Eleanor I; Wilkins, Diana G; Sherwin, Catherine M T

2017-12-01

Nicotine addiction is an issue faced by millions of individuals worldwide. As a result, nicotine replacement therapies, such as transdermal nicotine patches, have become widely distributed and used. While the pharmacokinetics of transdermal nicotine have been extensively described using noncompartmental methods, there are few data available describing the between-subject variability in transdermal nicotine pharmacokinetics. The aim of this investigation was to use population pharmacokinetic techniques to describe this variability, particularly as it pertains to the absorption of nicotine from the transdermal patch. A population pharmacokinetic parent-metabolite model was developed using plasma concentrations from 25 participants treated with transdermal nicotine. Covariates tested in this model included: body weight, body mass index, body surface area (calculated using the Mosteller equation) and sex. Nicotine pharmacokinetics were best described with a one-compartment model with absorption based on a Weibull distribution and first-order elimination and a single compartment for the major metabolite, cotinine. Body weight was a significant covariate on apparent volume of distribution of nicotine (exponential scaling factor 1.42). After the inclusion of body weight in the model, no other covariates were significant. This is the first population pharmacokinetic model to describe the absorption and disposition of transdermal nicotine and its metabolism to cotinine and the pharmacokinetic variability between individuals who were administered the patch. © 2017 The British Pharmacological Society.

Assessing nicotine dependence in adolescent E-cigarette users: The 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Nicotine Dependence Item Bank for electronic cigarettes.

PubMed

Morean, Meghan E; Krishnan-Sarin, Suchitra; S O'Malley, Stephanie

2018-04-26

Adolescent e-cigarette use (i.e., "vaping") likely confers risk for developing nicotine dependence. However, there have been no studies assessing e-cigarette nicotine dependence in youth. We evaluated the psychometric properties of the 4-item Patient-Reported Outcomes Measurement Information System Nicotine Dependence Item Bank for E-cigarettes (PROMIS-E) for assessing youth e-cigarette nicotine dependence and examined risk factors for experiencing stronger dependence symptoms. In 2017, 520 adolescent past-month e-cigarette users completed the PROMIS-E during a school-based survey (50.5% female, 84.8% White, 16.22[1.19] years old). Adolescents also reported on sex, grade, race, age at e-cigarette use onset, vaping frequency, nicotine e-liquid use, and past-month cigarette smoking. Analyses included conducting confirmatory factor analysis and examining the internal consistency of the PROMIS-E. Bivariate correlations and independent-samples t-tests were used to examine unadjusted relationships between e-cigarette nicotine dependence and the proposed risk factors. Regression models were run in which all potential risk factors were entered as simultaneous predictors of PROMIS-E scores. The single-factor structure of the PROMIS-E was confirmed and evidenced good internal consistency. Across models, larger PROMIS-E scores were associated with being in a higher grade, initiating e-cigarette use at an earlier age, vaping more frequently, using nicotine e-liquid (and higher nicotine concentrations), and smoking cigarettes. Adolescent e-cigarette users reported experiencing nicotine dependence, which was assessed using the psychometrically sound PROMIS-E. Experiencing stronger nicotine dependence symptoms was associated with characteristics that previously have been shown to confer risk for frequent vaping and tobacco cigarette dependence. Copyright © 2018 Elsevier B.V. All rights reserved.

BEHAVIORAL MECHANISMS UNDERLYING NICOTINE REINFORCEMENT

PubMed Central

Rupprecht, Laura E.; Smith, Tracy T.; Schassburger, Rachel L.; Buffalari, Deanne M.; Sved, Alan F.; Donny, Eric C.

2015-01-01

Cigarette smoking is the leading cause of preventable deaths worldwide and nicotine, the primary psychoactive constituent in tobacco, drives sustained use. The behavioral actions of nicotine are complex and extend well beyond the actions of the drug as a primary reinforcer. Stimuli that are consistently paired with nicotine can, through associative learning, take on reinforcing properties as conditioned stimuli. These conditioned stimuli can then impact the rate and probability of behavior and even function as conditioning reinforcers that maintain behavior in the absence of nicotine. Nicotine can also act as a conditioned stimulus, predicting the delivery of other reinforcers, which may allow nicotine to acquire value as a conditioned reinforcer. These associative effects, establishing non-nicotine stimuli as conditioned stimuli with discriminative stimulus and conditioned reinforcing properties as well as establishing nicotine as a conditioned stimulus, are predicted by basic conditioning principles. However, nicotine can also act non-associatively. Nicotine directly enhances the reinforcing efficacy of other reinforcing stimuli in the environment, an effect that does not require a temporal or predictive relationship between nicotine and either the stimulus or the behavior. Hence, the reinforcing actions of nicotine stem both from the primary reinforcing actions of the drug (and the subsequent associative learning effects) as well as the reinforcement enhancement action of nicotine which is non-associative in nature. Gaining a better understanding of how nicotine impacts behavior will allow for maximally effective tobacco control efforts aimed at reducing the harm associated with tobacco use by reducing and/or treating its addictiveness. PMID:25638333

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism.

PubMed

Dubroff, Jacob G; Doot, Robert K; Falcone, Mary; Schnoll, Robert A; Ray, Riju; Tyndale, Rachel F; Brody, Arthur L; Hou, Catherine; Schmitz, Alexander; Lerman, Caryn

2015-11-01

The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (α4β2* subtype) availability using PET imaging of the radiotracer 2-(18)F-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-(18)F-FA-85380, or 2-(18)F-FA). Twenty-four smokers-12 slow metabolizers (NMR < 0.26) and 12 normal metabolizers (NMR ≥ 0.26)-underwent 2-(18)F-FA-PET brain imaging after overnight nicotine abstinence (18 h before scanning), using a validated bolus-plus-infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest, with total distribution volume (VT/fP) being the measure of nAChR availability. Cravings to smoke were assessed before and after the scans. Thalamic nAChR α4β2* availability was significantly reduced in slow nicotine metabolizers (P = 0.04). Slow metabolizers exhibited greater reductions in cravings after scanning than normal metabolizers; however, craving was unrelated to nAChR availability. The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies the differences in treatment response between slow and normal metabolizers of nicotine. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

10 CFR 835.209 - Concentrations of radioactive material in air.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Concentrations of radioactive material in air. 835.209 Section 835.209 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External Exposure § 835.209 Concentrations of radioactive material in air. (a) The derived air...

10 CFR 835.209 - Concentrations of radioactive material in air.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Concentrations of radioactive material in air. 835.209 Section 835.209 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External Exposure § 835.209 Concentrations of radioactive material in air. (a) The derived air...

10 CFR 835.209 - Concentrations of radioactive material in air.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Concentrations of radioactive material in air. 835.209 Section 835.209 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External Exposure § 835.209 Concentrations of radioactive material in air. (a) The derived air...

10 CFR 835.209 - Concentrations of radioactive material in air.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Concentrations of radioactive material in air. 835.209 Section 835.209 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External Exposure § 835.209 Concentrations of radioactive material in air. (a) The derived air...

Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

PubMed

Pushparaj, Abhiram; Hamani, Clement; Yu, Wilson; Shin, Damian S; Kang, Bin; Nobrega, José N; Le Foll, Bernard

2013-03-01

Pharmacological inactivation of the granular insular cortex is able to block nicotine-taking and -seeking behaviors in rats. In this study, we explored the potential of modulating activity in the insular region using electrical stimulation. Animals were trained to self-administer nicotine (0.03 mg/kg per infusion) under a fixed ratio-5 (FR-5) schedule of reinforcement followed by a progressive ratio (PR) schedule. Evaluation of the effect of stimulation in the insular region was performed on nicotine self-administration under FR-5 and PR schedules, as well on reinstatement of nicotine-seeking behavior induced by nicotine-associated cues or nicotine-priming injections. The effect of stimulation was also examined in brain slices containing insular neurons. Stimulation significantly attenuated nicotine-taking, under both schedules of reinforcement, as well as nicotine-seeking behavior induced by cues and priming. These effects appear to be specific to nicotine-associated behaviors, as stimulation did not have any effect on food-taking behavior. They appear to be anatomically specific, as stimulation surrounding the insular region had no effect on behavior. Stimulation of brain slices containing the insular region was found to inactivate insular neurons. Our results suggest that deep brain stimulation to modulate insular activity should be further explored.

The linear relationship between cigarette tar and nicotine yields: regulatory implications for smoke constituent ratios.

PubMed

St Charles, F K; Cook, C J; Clayton, P M

2011-02-01

Cigarette smoke analyte yields are often expressed as ratios relative to tar or nicotine yields, usually to compare different products or to estimate human uptake of smoke in relation to nicotine uptake measurements. The method, however, can lead to distorted interpretations, especially in the case of ratios from ultra-low tar yield cigarettes. In brief, as tar yields decrease below the 5–6 mg per cigarette range, the tar-to-nicotine ratio (TNR) decreases rapidly in a non-linear fashion. If, however, the nicotine yield, rather than the ratio, is plotted versus the tar yield, the non-linearity disappears and a straight line is obtained, with a slight positive intercept for nicotine on the ordinate. Unlike the ratio, the slope appears to depend only on the concentration of the nicotine in the blend and does not appear to vary with smoking parameters such as puff volume, puff interval or length smoked or with cigarette design parameters such as length, circumference or the amount of filtration or filter ventilation. Therefore, such a slope is analogous to the TNR although, unlike that ratio, it is invariant. Even more simply, the concentration of the nicotine in the blend, at least for American blend-style cigarettes, provides a similar index.

Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking

PubMed Central

Ross, Kathryn C.; Gubner, Noah R.; Tyndale, Rachel F.; Hawk, Larry W.; Lerman, Caryn; George, Tony P.; Cinciripini, Paul; Schnoll, Robert A.; Benowitz, Neal L.

2016-01-01

Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity. Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers. There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites. The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure. Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed. The results indicated that rate of nicotine metabolism is a more important factor influencing nicotine intake in White smokers. Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine. However, this relationship was not found in African Americans. Overall there was a greater step down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers. PMID:27180107

Fractional kalman filter to estimate the concentration of air pollution

NASA Astrophysics Data System (ADS)

Vita Oktaviana, Yessy; Apriliani, Erna; Khusnul Arif, Didik

2018-04-01

Air pollution problem gives important effect in quality environment and quality of human’s life. Air pollution can be caused by nature sources or human activities. Pollutant for example Ozone, a harmful gas formed by NOx and volatile organic compounds (VOCs) emitted from various sources. The air pollution problem can be modeled by TAPM-CTM (The Air Pollution Model with Chemical Transport Model). The model shows concentration of pollutant in the air. Therefore, it is important to estimate concentration of air pollutant. Estimation method can be used for forecast pollutant concentration in future and keep stability of air quality. In this research, an algorithm is developed, based on Fractional Kalman Filter to solve the model of air pollution’s problem. The model will be discretized first and then it will be estimated by the method. The result shows that estimation of Fractional Kalman Filter has better accuracy than estimation of Kalman Filter. The accuracy was tested by applying RMSE (Root Mean Square Error).

Nicotine Addiction and Psychiatric Disorders

PubMed Central

Kutlu, Munir Gunes; Parikh, Vinay; Gould, Thomas J.

2017-01-01

Even though smoking rates have long been on the decline, nicotine addiction still affects 20% of the US population today. Moreover, nicotine dependence shows high comorbidity with many mental illnesses including, but are not limited to, attention deficit hyperactivity disorder, anxiety disorders, and depression. The reason for the high rates of smoking in patients with mental illnesses may relate to attempts to self-medicate with nicotine. While nicotine may alleviate the symptoms of mental disorders, nicotine abstinence has been shown to worsen the symptoms of these disorders. In this chapter, we review the studies from animal and human research examining the bidirectional relationship between nicotine and attention deficit hyperactivity disorder, anxiety disorders, and depression as well as studies examining the roles of specific subunits of nicotinic acetylcholine receptors (nAChRs) in the interaction between nicotine and these mental illnesses. The results of these studies suggest that activation, desensitization, and upregulation of nAChRs modulate the effects of nicotine on mental illnesses. PMID:26472530

Nicotine Inhibits Memory CTL Programming

PubMed Central

Sun, Zhifeng; Smyth, Kendra; Garcia, Karla; Mattson, Elliot; Li, Lei; Xiao, Zhengguo

2013-01-01

Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs) and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development. PMID:23844169

Chronic Nicotine Treatment During Adolescence Attenuates the Effects of Acute Nicotine in Adult Contextual Fear Learning.

PubMed

Holliday, Erica D; Gould, Thomas J

2017-01-01

Adolescent onset of nicotine abuse is correlated with worse chances at successful abstinence in adulthood. One reason for this may be due to enduring learning deficits resulting from nicotine use during adolescence. Previous work has indicated that chronic nicotine administration beginning in late adolescence (PND38) caused learning deficits in contextual fear when tested in adulthood. The purpose of this study was to determine if chronic nicotine treatment during adolescence would alter sensitivity to nicotine's cognitive enhancing properties in adulthood. C57BL/6J mice received saline or chronic nicotine (12.6mg/kg/day) during adolescence (postnatal day 38) or adulthood (postnatal day 54) for a period of 12 days. Following a 30-day protracted abstinence, mice received either an acute injection of saline or nicotine (0.045, 0.18, and 0.36mg/kg) prior to training and testing a mouse model of contextual fear. It was found that chronic nicotine administration in adult mice did not alter sensitivity to acute nicotine following a protracted abstinence. In adolescent mice, chronic nicotine administration disrupted adult learning and decreased sensitivity to acute nicotine in adulthood as only the highest dose tested (0.36mg/kg) was able to enhance contextual fear learning. These results suggest that adolescent nicotine exposure impairs learning in adulthood, which could increase the risk for continued nicotine use in adulthood by requiring administration of higher doses of nicotine to reverse learning impairments caused by adolescent nicotine exposure. Results from this study add to the growing body of literature suggesting chronic nicotine exposure during adolescence leads to impaired learning in adulthood and demonstrates that nicotine exposure during adolescence attenuates the cognitive enhancing effects of acute nicotine in adulthood, which suggests altered cholinergic function. © The Author 2016. Published by Oxford University Press on behalf of the Society for

The role of nicotine content information in smokers' subjective responses to nicotine and placebo inhalers.

PubMed

Darredeau, Christine; Barrett, Sean P

2010-11-01

A growing body of evidence suggests that non-pharmacological factors may play an important role in smoking cessation outcomes using nicotine replacement therapies. This study examined the role of information about nicotine content in smokers' subjective responses to nicotine and placebo inhalers, using the four conditions of the balanced-placebo design in a mixed within/between-subjects design. Twenty-four adult smokers (12 male) completed two laboratory sessions following overnight abstinence from smoking. Participants were randomly assigned to receive either nicotine inhalers or placebo inhalers in both sessions but were told that they received a nicotine-containing inhaler in one session and a nicotine-free inhaler in the other. In each session participants completed subjective assessments before and after inhaler administration using visual analogue scales and the Brief Questionnaire of Smoking Urges. While neither nicotine content nor information about it significantly affected cigarette craving associated with withdrawal relief, participants reported a greater reduction in craving associated with intention to smoke when told the inhalers contained nicotine than when told the inhalers were nicotine-free, regardless of actual nicotine content. Findings suggest that psychological factors play an important role in smokers' subjective responses to nicotine inhalers, the effects of which cannot be solely attributed to the direct pharmacological effects of nicotine. Copyright © 2011 John Wiley & Sons, Ltd.

The role of nicotinic receptor beta-2 subunits in nicotine discrimination and conditioned taste aversion.

PubMed

Shoaib, M; Gommans, J; Morley, A; Stolerman, I P; Grailhe, R; Changeux, J-P

2002-03-01

The subtypes of nicotinic receptors at which the behavioural effects of nicotine originate are not fully understood. These experiments use mice lacking the beta2 subunit of nicotinic receptors to investigate its role in nicotine discrimination and conditioned taste aversion (CTA). Wild-type and mutant mice were trained either in a two-lever nicotine discrimination procedure using a tandem schedule of food reinforcement, or in a counterbalanced two-flavour CTA procedure. Rates of lever-pressing of wild-type and mutant mice did not differ. Wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) rapidly and exhibited steep dose-response curves. Mutant mice failed to acquire these nicotine discriminations and exhibited flat dose-response curves. Both wild-type and mutant mice acquired discrimination of nicotine (1.6 mg/kg) although discrimination performance was weak in the mutants. Nicotine initially reduced response rates in wild-type and mutant mice, and tolerance developed to this effect in each genotype. Both genotypes acquired discrimination of morphine (3 mg/kg) with similar degrees of accuracy, and dose-response curves for morphine discrimination in the two genotypes were indistinguishable. Nicotine produced dose-related CTA in both genotypes, but the magnitude of the effect was less in the mutants than in the wild-type controls. It is concluded that nicotinic receptors containing the beta2 subunit play a major role in the discriminative stimulus and taste aversion effects of nicotine that may reflect psychological aspects of tobacco dependence. Such receptors appear to have a less crucial role in the response-rate, reducing effects of nicotine and in nicotine tolerance.

[Elimination of volatile compounds of leaf tobacco from air emissions using biofiltration].

PubMed

Zagustina, N A; Misharina, T A; Vepritskiĭ, A A; Zhukov, V G; Ruzhitskiĭ, A O; Terenina, M B; Krikunova, N I; Kulikova, A K; Popov, V O

2012-01-01

The composition of the volatile organic compounds (VOCs) of various leaf tobacco brands and their blends has been studied. The differences in the content of nicotine, solanone, tetramethyl hexadecenol, megastigmatrienones, and other compounds, determining the specific tobacco smell, have been revealed. A microbial consortium, which is able to deodorize simulated tobacco emissions and decompose nicotine, has been formed by long-term adaptation to the VOCs of tobacco leaves in a laboratory reactor, functioning as a trickle-bed biofilter. Such a biofilter eliminates 90% of the basic toxic compound (nicotine) and odor-active compounds; the filtration efficiency does not change for tobacco brands with different VOC concentrations or in the presence of foreign substances. The main strains, isolated from the formed consortium and participating in the nicotine decomposition process, belong to the genera Pseudomonas, Bacillus, and Rhodococcus. An examination of the biofilter trickling fluid has shown full decomposition of nicotine and odor-active VOCs. The compounds, revealed in the trickling fluid, did not have any odor and were nontoxic. The obtained results make it possible to conduct scaling of the biofiltration process to eliminate odor from air emissions in the tobacco industry.

Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice.

PubMed

Locker, Alicia R; Marks, Michael J; Kamens, Helen M; Klein, Laura Cousino

2016-05-01

Nearly 80% of adult smokers begin smoking during adolescence. Binge alcohol consumption is also common during adolescence. Past studies report that nicotine and ethanol activate dopamine neurons in the reward pathway and may increase synaptic levels of dopamine in the nucleus accumbens through nicotinic acetylcholine receptor (nAChR) stimulation. Activation of the reward pathway during adolescence through drug use may produce neural alterations affecting subsequent drug consumption. Consequently, the effect of nicotine exposure on binge alcohol consumption was examined along with an assessment of the neurobiological underpinnings that drive adolescent use of these drugs. Adolescent C57BL/6J mice (postnatal days 35-44) were exposed to either water or nicotine (200μg/ml) for ten days. On the final four days, ethanol intake was examined using the drinking-in-the-dark paradigm. Nicotine-exposed mice consumed significantly more ethanol and displayed higher blood ethanol concentrations than did control mice. Autoradiographic analysis of nAChR density revealed higher epibatidine binding in frontal cortical regions in mice exposed to nicotine and ethanol compared to mice exposed to ethanol only. These data show that nicotine exposure during adolescence increases subsequent binge ethanol consumption, and may affect the number of nAChRs in regions of the brain reward pathway, specifically the frontal cortex. Published by Elsevier Inc.

Transport phenomena governing nicotine emissions from electronic cigarettes: model formulation and experimental investigation

PubMed Central

Talih, Soha; Balhas, Zainab; Salman, Rola; El-Hage, Rachel; Karaoghlanian, Nareg; El-Hellani, Ahmad; Baassiri, Mohamad; Jaroudi, Ezzat; Eissenberg, Thomas; Saliba, Najat; Shihadeh, Alan

2017-01-01

Electronic cigarettes (ECIGs) electrically heat and aerosolize a liquid containing propylene glycol (PG), vegetable glycerin (VG), flavorants, water, and nicotine. ECIG effects and proposed methods to regulate them are controversial. One regulatory focal point involves nicotine emissions. We describe a mathematical model that predicts ECIG nicotine emissions. The model computes the vaporization rate of individual species by numerically solving the unsteady species and energy conservation equations. To validate model predictions, yields of nicotine, total particulate matter, PG, and VG were measured while manipulating puff topography, electrical power, and liquid composition across 100 conditions. Nicotine flux, the rate at which nicotine is emitted per unit time, was the primary outcome. Across conditions, the measured and computed nicotine flux were highly correlated (r = 0.85, p<.0001). As predicted, device power, nicotine concentration, PG/VG ratio, and puff duration influenced nicotine flux (p<.05), while water content and puff velocity did not. Additional empirical investigation revealed that PG/VG liquids act as ideal solutions, that liquid vaporization accounts for more than 95% of ECIG aerosol mass emissions, and that as device power increases the aerosol composition shifts towards the less volatile components of the parent liquid. To the extent that ECIG regulations focus on nicotine emissions, mathematical models like this one can be used to predict ECIG nicotine emissions and to test the effects of proposed regulation of factors that influence nicotine flux. PMID:28706340

Nicotine and Nicotine Abstinence Do Not Interfere with GABAA Receptor Neuroadaptations During Alcohol Abstinence.

PubMed

Hillmer, Ansel T; Kloczynski, Tracy; Sandiego, Christine M; Pittman, Brian; Anderson, Jon M; Labaree, David; Gao, Hong; Huang, Yiyun; Deluliis, Giuseppe; O'Malley, Stephanie S; Carson, Richard E; Cosgrove, Kelly P

2016-04-01

Alcohol dependence and tobacco smoking are highly comorbid, and treating both conditions simultaneously is controversial. Previously, we showed that tobacco smoking interferes with GABAA receptor neuroadaptations during alcohol withdrawal in humans, while this effect did not occur with continued nicotine use during alcohol abstinence in nonhuman primates. Here, we extend our previous work by measuring GABAA receptor availability with positron emission tomography (PET) during drug abstinence in nonhuman primates exposed to alcohol alone, nicotine and alcohol together, and alcohol abstinence with continued nicotine exposure. Twenty-four adolescent male rhesus macaques orally self-administered alcohol and nicotine, available separately in water and saccharin, over 20 weeks. The groups included alcohol alone (n = 8); nicotine and alcohol with simultaneous abstinence (n = 8); nicotine and alcohol with alcohol abstinence while nicotine was still available (n = 8); and a pilot group of animals consuming nicotine alone (n = 6). Animals were imaged with [(11)C]flumazenil PET to measure binding potential (BPND), an index of GABAA receptor availability. Imaging occurred at baseline (drug-naíve), and following alcohol and/or nicotine cessation at 1 day, 8 days, and 12 weeks of abstinence. Generalized linear mixed models were used to examine the time course of [(11)C]flumazenil BPND during alcohol abstinence across groups. Animals consumed 3.95 ± 1.22 g/kg/d alcohol and 55.4 ± 35.1 mg/kg/d nicotine. No significant group effects were observed in [(11)C]flumazenil BPND during alcohol abstinence; however, a main effect of time was detected. Post hoc analyses indicated that all groups abstaining from alcohol exhibited significantly increased GABAA receptor availability at 1 day and 8 days (but not 12 weeks) of abstinence relative to baseline, while no changes in [(11)C]flumazenil BPND during nicotine abstinence alone were observed. These data indicate that neither nicotine nor

Effects of chronic buspirone treatment on nicotine and concurrent nicotine+cocaine self-administration.

PubMed

Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J

2013-06-01

Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal pharmacotherapy would reduce both cigarette smoking and cocaine abuse. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on serotonin and dopamine systems. In preclinical studies, it reduced cocaine self-administration following both acute and chronic treatment in rhesus monkeys. The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of intravenous (IV) nicotine and IV nicotine+cocaine combinations. Five cocaine-experienced adult rhesus monkeys (Macaca mulatta) were trained to self-administer nicotine or nicotine+cocaine combinations, and food pellets (1 g) during four 1-h daily sessions under a second-order schedule of reinforcement (FR 2 (VR16:S)). Each nicotine+cocaine combination maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05-0.001). Buspirone (0.032-0.56 mg/kg/h) was administered IV through one lumen of a double-lumen catheter every 20 min for 23 h each day, for 7-10 consecutive days. Each 7-10-day sequence of buspirone treatment was followed by saline-control treatment for at least 3 days until food- and drug-maintained responding returned to baseline. Buspirone dose-dependently reduced responding maintained by nicotine alone (0.001-0.1 mg/kg/inj; P<0.01) and by nicotine (0.001 or 0.0032 mg/kg/inj)+cocaine combinations (0.0032 mg/kg/inj; P<0.05-0.001) with no significant effects on food-maintained responding. We conclude that buspirone selectively attenuates the reinforcing effects of nicotine alone and nicotine+cocaine polydrug combinations in a nonhuman primate model of drug self-administration.

Effects of Chronic Buspirone Treatment on Nicotine and Concurrent Nicotine+Cocaine Self-Administration

PubMed Central

Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J

2013-01-01

Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal pharmacotherapy would reduce both cigarette smoking and cocaine abuse. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on serotonin and dopamine systems. In preclinical studies, it reduced cocaine self-administration following both acute and chronic treatment in rhesus monkeys. The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of intravenous (IV) nicotine and IV nicotine+cocaine combinations. Five cocaine-experienced adult rhesus monkeys (Macaca mulatta) were trained to self-administer nicotine or nicotine+cocaine combinations, and food pellets (1 g) during four 1-h daily sessions under a second-order schedule of reinforcement (FR 2 (VR16:S)). Each nicotine+cocaine combination maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05–0.001). Buspirone (0.032–0.56 mg/kg/h) was administered IV through one lumen of a double-lumen catheter every 20 min for 23 h each day, for 7–10 consecutive days. Each 7–10-day sequence of buspirone treatment was followed by saline-control treatment for at least 3 days until food- and drug-maintained responding returned to baseline. Buspirone dose-dependently reduced responding maintained by nicotine alone (0.001–0.1 mg/kg/inj; P<0.01) and by nicotine (0.001 or 0.0032 mg/kg/inj)+cocaine combinations (0.0032 mg/kg/inj; P<0.05–0.001) with no significant effects on food-maintained responding. We conclude that buspirone selectively attenuates the reinforcing effects of nicotine alone and nicotine+cocaine polydrug combinations in a nonhuman primate model of drug self-administration. PMID:23337868

Pharmacokinetics of nicotine in rats after multiple-cigarette smoke exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rotenberg, K.S.; Adir, J.

1983-06-15

The pharmacokinetics of nicotine and its major metabolites was evaluated in male rats after multiple-cigarette smoke exposure. A smoke-exposure apparatus was used to deliver cigarette smoke to the exposure chamber. The rats were exposed to smoke from a single cigarette every 8 hr for 14 days and to the smoke of a cigarette spiked with radiolabeled nicotine on the 15th day. Blood and urine samples were collected at timed intervals during the 10-min smoke-exposure period of the last cigarette and up to 48 hr thereafter. Nicotine, cotinine, and other polar metabolites were separated by thin-layer chromatography and quantified by liquidmore » scintillation counting. The data were analyzed by computer fitting, and the derived pharmacokinetic parameters were compared to those observed after a single iv injection of nicotine and after a single-cigarette smoke exposure. The results indicated that the amount of nicotine absorbed from multiple-cigarette smoke was approximately 10-fold greater than that absorbed from a single cigarette. Also, unlike the single-cigarette smoke exposure experiment, nicotine plasma levels did not decay monotonically but increased after the 5th hr, and high plasma concentrations persisted for 30 hr. The rate and extent of the formation of cotinine, the major metabolite of nicotine, were decreased as compared with their values following a single-cigarette smoke exposure. It was concluded that nicotine or a constituent of tobacco smoke inhibits the formation of cotinine and may affect the biotransformation of other metabolites. Urinary excretion tended to support the conclusions that the pharmacokinetic parameters of nicotine and its metabolites were altered upon multiple as compared to single dose exposure.« less

Nicotine stimulation increases proliferation and matrix metalloproteinases-2 and -28 expression in human dental pulp cells.

PubMed

Manuela, Rizzi; Mario, Migliario; Vincenzo, Rocchetti; Filippo, Renò

2015-08-15

Dental pulp is the specialized tissue responsible for maintaining tooth viability. When tooth mineralized matrix is damaged, pulp is exposed to a plethora of environmental stimuli. In particular, in smokers, pulp become exposed to very high concentrations of nicotine. The aim of this study was to investigate the effect of direct nicotine stimulation on human dental pulp cell proliferation. Moreover, as it is known that nicotine could upregulate the expression of matrix metalloproteinases (MMPs), enzymes involved in pulpal inflammation, the effects of nicotine stimulation on MMP-2 and MMP-28 gene expression have also been investigated. Human dental pulp cells were extracted from impacted third molars obtained from healthy patients undergoing routine orthodontic treatments. Such cells were treated with growing concentrations of nicotine in the presence or absence of a nicotine antagonist (hexamethonium chloride) or of a MEK signaling inhibitor (PD98059). Cell proliferation was evaluated by cell counting, while nicotine effects on MMP expression were evaluated by PCR. The data obtained indicate that nicotine is able to increase human dental pulp cell proliferation by acting through nicotinic cholinergic receptors and downstream MAPK signaling pathway. Moreover, it is also able to increase both MMP-2 and MMP-28 gene expression. In summary these results highlight that direct exposure of human dental pulp cells to nicotine results in an inflammatory response, that could have a role in pulpal inflammation onset, a pathological condition that, when ignored, could eventually spread to the surrounding alveolar bone and progress to pulp necrosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Simultaneous determination of nicotine, cotinine, and nicotine N-oxide in human plasma, semen, and sperm by LC-Orbitrap MS.

PubMed

Abu-Awwad, Ahmad; Arafat, Tawfiq; Schmitz, Oliver J

2016-09-01

Nicotine (Nic) distribution in human fluids and tissues has a deleterious effect on human health. In addition to its poisoning profile, Nic may contribute to the particular impact of smoking on human reproduction. Although present in seminal fluid, still nobody knows whether nicotine is available in sperm or not. Herein, we developed and validated a new bioanalytical method, for simultaneous determination of Nic, cotinine (Cot), and nicotine N'-oxide (Nox) in human plasma, semen, and sperm by LC-ESI-orbitrap-MS. Blood and semen samples were collected from 12 healthy smoking volunteers in this study. Sperm bodies were then separated quantitatively from 1 mL of semen samples by centrifugation. The developed method was fully validated for plasma following European and American guidelines for bioanalytical method validation, and partial validation was applied to semen analysis. Plasma, semen, and sperm samples were treated by trichloroacetic acid solution for protein direct precipitation in single extraction step. The established calibration range for Nic and Nox in plasma and semen was linear between 5 and 250 ng/mL, and for Cot between 10 and 500 ng/mL. Nic and Cot were detected in human sperm at concentrations as high as in plasma. In addition, Nox was present in semen and sperm but not in plasma. Graphical abstract Nicotine correlation between plasma and semen a; Nicotine correlation between semen and sperm c; Cotinine correlation between plasma and semen b; Cotinine correlation between semen and sperm d.

Nicotine Lozenges

MedlinePlus

Nicotine lozenges may cause side effects. Tell your doctor if either of these symptoms is severe or does not go away: heartburn ... doctor immediately: mouth problems irregular or fast heartbeat Nicotine lozenges may cause other side effects. Call your doctor if you have any unusual ...

Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

PubMed

Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

2017-07-01

The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

Nicotine delivery and pharmacologic response from Verve, an oral nicotine delivery product☆

PubMed Central

Koszowski, Bartosz; Viray, Lauren C.; Stanfill, Stephen B.; Lisko, Joseph G.; Rosenberry, Zach R.; Potts, Jennifer L.; Pickworth, Wallace B.

2016-01-01

Verve, an oral nicotine delivery product (ONDP), was introduced by Nu Mark (Altria Client Group, Richmond VA) for smokers to use in places where smoking is prohibited. This study assessed the effect of this ONDP on plasma nicotine levels, heart rate, product satisfaction, and ability to suppress smoking urge and cigarette cravings. Thirteen daily cigarette smokers [8 men and 5 women; average age 33.4 years] attended two laboratory sessions, one occurred after overnight tobacco abstinence. Plasma samples were collected before and after ONDP use and measured for nicotine. In non-abstinent smokers, mean plasma nicotine levels increased from 18.3 to 21.0 ng/mL. In abstinent smokers, average nicotine levels increased from 3.1 to 4.5 ng/mL. After overnight tobacco abstinence, ONDP use significantly (p < 0.01) increased heart rate from 69 beats per minute (bpm) to 75 bpm; while urge to smoke decreased significantly (p < 0.01) from a score of 8.6 to 4.9. Participants indicated moderate product satisfaction that was not changed by tobacco abstinence. Analysis of unused ONDP revealed total nicotine levels of 1.68 ± 0.09 mg/disc. Spent ONDP discs were also analyzed to determine % nicotine liberated during chewing; results were 80% in the non-abstinent and 82% in the abstinent conditions (ns). Our study results indicate that ONDP use can increase plasma nicotine levels and heart rate and reduce cigarette cravings in abstinent smokers. PMID:26096037

Nicotine delivery and pharmacologic response from Verve, an oral nicotine delivery product.

PubMed

Koszowski, Bartosz; Viray, Lauren C; Stanfill, Stephen B; Lisko, Joseph G; Rosenberry, Zach R; Potts, Jennifer L; Pickworth, Wallace B

2015-09-01

Verve, an oral nicotine delivery product (ONDP), was introduced by Nu Mark (Altria Client Group, Richmond VA) for smokers to use in places where smoking is prohibited. This study assessed the effect of this ONDP on plasma nicotine levels, heart rate, product satisfaction, and ability to suppress smoking urge and cigarette cravings. Thirteen daily cigarette smokers [8 men and 5 women; average age 33.4years] attended two laboratory sessions, one occurred after overnight tobacco abstinence. Plasma samples were collected before and after ONDP use and measured for nicotine. In non-abstinent smokers, mean plasma nicotine levels increased from 18.3 to 21.0ng/mL. In abstinent smokers, average nicotine levels increased from 3.1 to 4.5ng/mL. After overnight tobacco abstinence, ONDP use significantly (p<0.01) increased heart rate from 69beats per minute (bpm) to 75bpm; while urge to smoke decreased significantly (p<0.01) from a score of 8.6 to 4.9. Participants indicated moderate product satisfaction that was not changed by tobacco abstinence. Analysis of unused ONDP revealed total nicotine levels of 1.68±0.09mg/disc. Spent ONDP discs were also analyzed to determine % nicotine liberated during chewing; results were 80% in the non-abstinent and 82% in the abstinent conditions (ns). Our study results indicate that ONDP use can increase plasma nicotine levels and heart rate and reduce cigarette cravings in abstinent smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

Hyoscine butylbromide potently blocks human nicotinic acetylcholine receptors in SH-SY5Y cells.

PubMed

Weiser, Thomas; Just, Stefan

2009-02-06

Hyoscine butylbromide (HBB; tradenames: Buscopan/Buscapina is an antispasmodic drug for the treatment of abdominal pain associated with gastrointestinal cramping. As a hyoscine derivative, this compound competitively inhibits muscarinic acetylcholine (ACh) receptors on smooth muscle cells in the gastrointestinal tract. Preliminary investigations suggested that it might also inhibit nicotinic ACh receptors. This study investigated the effect of HBB on nicotinic ACh receptor-mediated membrane currents in SH-SY5Y cells. ACh and nicotine application-induced comparable membrane currents with EC(50) values of 25.9+/-0.6 and 40.1+/-0.4microM, respectively. When coapplied with 100microM ACh, HBB concentration-dependently suppressed currents with an IC(50) value of 0.19+/-0.04microM, and was approximately seven-times more potent than the ganglionic blocker, hexamethonium (IC(50)=1.3+/-0.3microM). Increasing the agonist concentration to 5mM did not affect the amount of block by HBB, which suggests a non-competitive mode of action. These functional in vitro data demonstrate for the first time that HBB blocks neuronal nicotinic ACh receptors in the same concentration range as it inhibits muscarinic ACh receptors. If one hypothesizes that HBB might also affect nicotinic receptors in autonomic neurons in vivo (e. g. in the enteric nervous system), this effect could contribute to its spasmolytic activity.

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

PubMed Central

Garcia-Arcos, Itsaso; Geraghty, Patrick; Baumlin, Nathalie; Campos, Michael; Dabo, Abdoulaye Jules; Jundi, Bakr; Cummins, Neville; Eden, Edward; Grosche, Astrid; Salathe, Matthias; Foronjy, Robert

2016-01-01

Background The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells. Methods Mice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot. Results Inhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion. Conclusions Exposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use. PMID:27558745

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner.

PubMed

Garcia-Arcos, Itsaso; Geraghty, Patrick; Baumlin, Nathalie; Campos, Michael; Dabo, Abdoulaye Jules; Jundi, Bakr; Cummins, Neville; Eden, Edward; Grosche, Astrid; Salathe, Matthias; Foronjy, Robert

2016-12-01

The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells. Mice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot. Inhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion. Exposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Honey Attenuates the Detrimental Effects of Nicotine on Testicular Functions in Nicotine Treated Wistar Rats.

PubMed

Kolawole, T A; Oyeyemi, W A; Adigwe, C; Leko, B; Udeh, C; Dapper, D V

2015-12-20

Effect of honey on reproductive functions of male rats exposed to nicotine was examined in this study. Thirty-two adult male wistar rats (n=8/Group) were grouped as Control (distilled water), Nicotine (1.0mg/kg bwt), Honey (100mg/kg bwt) and Nicotine with Honey. The animals were orally treated for 35 days consecutively. Epididymis sperm motility, viability, morphology and counts were estimated, serum Follicle Stimulating Hormone (FSH), Leutinizing Hormone (LH) and Testosterone were assayed using ELISA method and testicular histology were also assessed. Significant reduction in percentage sperm motility, viability, morphology and counts were observed in nicotine group compared to control. Serum FSH, LH and testosterone levels were significantly reduced in nicotine group when compared with the control. There was significant improvement in sperm motility, viability, morphology, counts, FSH, LH and Testosterone in group co-treated with nicotine and honey  relative to nicotine group. Also, the degenerative seminiferous tubule architecture due to nicotine was improved by honey. In conclusion, honey may suppress nicotine toxic effect on reproductive functions in male Wistar rats.

Reduction of air pollutant concentrations in an indoor ice-skating rink

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, K.; Yanagisawa, Yukio; Spengler, J.D.

1994-01-01

High carbon monoxide and nitrogen dioxide concentrations were measured in an indoor ice-skating rink with fuel-powered ice-resurfacing equipment. In 22% to 33% of the measurements over 90-min segments, CO concentrations exceeded 20 [mu]L/L as a 90-min average in the absence of rink ventilation. Average NO[sub 2] concentrations over 14 h were higher than 600 nL/L. Reduction of air pollutant concentrations in the ice-skating rink is necessary to prevent air-pollutant-exposure-related health incidents. Various methods for reducing air pollutants in an ice-skating rink were evaluated by simultaneously measuring CO and NO[sub 2] concentrations. Single pollution reduction attempts, such as extension of themore » exhaust pipe, reduction in the number of resurfacer operations, or use of an air recirculation system, did not significantly reduce air pollutant concentrations in the rink. Full operation of the mechanical ventilation system combined with reduced resurfacer operation was required to keep the air pollutant levels in the skating rink below the recommended guidelines. This investigation showed that management of clean air quality in an ice-skating rink is practically difficult as long as fuel-powered resurfacing equipment is used. 16 refs., 3 figs., 5 tabs.« less

Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

PubMed

Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

2015-05-05

Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

Nicotine Gum

MedlinePlus

... every 1 to 2 hours for the first 6 weeks, followed by one piece every 2 to 4 hours for 3 weeks, ... chances of quitting smoking, chew at least 9 pieces of nicotine gum each day for the first 6 weeks.Chew nicotine gum slowly until you can ...

Nicotine inhibits collagen synthesis and alkaline phosphatase activity, but stimulates DNA synthesis in osteoblast-like cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramp, W.K.; Lenz, L.G.; Galvin, R.J.

1991-05-01

Use of smokeless tobacco is associated with various oral lesions including periodontal damage and alveolar bone loss. This study was performed to test the effects of nicotine on bone-forming cells at concentrations that occur in the saliva of smokeless tobacco users. Confluent cultures of osteoblast-like cells isolated from chick embryo calvariae were incubated for 2 days with nicotine added to the culture medium (25-600 micrograms/ml). Nicotine inhibited alkaline phosphatase in the cell layer and released to the medium, whereas glycolysis (as indexed by lactate production) was unaffected or slightly elevated. The effects on medium and cell layer alkaline phosphatase weremore » concentration dependent with maximal inhibition occurring at 600 micrograms nicotine/ml. Nicotine essentially did not affect the noncollagenous protein content of the cell layer, but did inhibit collagen synthesis (hydroxylation of ({sup 3}H)proline and collagenase-digestible protein) at 100, 300, and 600 micrograms/ml. Release of ({sup 3}H)hydroxyproline to the medium was also decreased in a dose-dependent manner, as was the collagenase-digestible protein for both the medium and cell layer. In contrast, DNA synthesis (incorporation of ({sup 3}H)thymidine) was more than doubled by the alkaloid, whereas total DNA content was slightly inhibited at 600 micrograms/ml, suggesting stimulated cell turnover. Morphologic changes occurred in nicotine-treated cells including rounding up, detachment, and the occurrence of numerous large vacuoles. These results suggest that steps to reduce the salivary concentration of nicotine in smokeless tobacco users might diminish damaging effects of this product on alveolar bone.« less

Reduction of nicotine self-administration by chronic nicotine infusion with H1 histamine blockade in female rats.

PubMed

Levin, Edward D; Hall, Brandon J; Chattopadhyay, Autri; Slade, Susan; Wells, Corinne; Rezvani, Amir H; Rose, Jed E

2016-08-01

Chronic nicotine infusion via transdermal patches has been widely shown to assist with smoking cessation. In particular, transdermal nicotine treatment prior to quitting smoking helps reduce ad libitum smoking and aids cessation Rose et al. (Nicotine Tob Res 11:1067-75, 2009). However, despite this success, the majority of smokers who use transdermal nicotine fail to permanently quit smoking. Additional treatments are needed. Tobacco addiction does not just depend on nicotinic receptor systems; a variety of neural systems are involved, including dopamine, norepinepherine, serotonin, and histamine. Given the involvement of a variety of neural systems in the circuits of addiction, combination therapy may offer improved efficacy for successful smoking cessation beyond single treatments alone. We have found that pyrilamine, an H1 histamine antagonist, significantly decreases nicotine self-administration in rats. The current study was conducted to confirm the effect of chronic nicotine infusion on ongoing nicotine self-administration and resumed access after enforced abstinence and to determine the interaction of chronic nicotine with an H1 antagonist treatment. Chronic nicotine infusion via osmotic minipump (2.5 and 5 mg/kg/day for 28 days) significantly reduced nicotine self-administration in a dose-dependent manner. Chronic nicotine infusion also reduced the resumption of nicotine self-administration after enforced abstinence. Chronic pyrilamine infusion (25 mg/kg/day for 14 days) also significantly reduced nicotine self-administration. The combination of chronic nicotine and pyrilamine reduced nicotine self-administration to a greater extent than treatment with either drug alone.

Effect of cigar smoking on carboxyhaemoglobin and plasma nicotine concentrations in primary pipe and cigar smokers and ex-cigarette smokers

PubMed Central

Turner, J A McM; Sillett, R W; McNicol, M W

1977-01-01

Five ex-cigarette smokers and five primary pipe and cigar smokers each smoked a large cigar. Carboxyhaemoglobin (COHb) and plasma nicotine levels were measured. In the ex-cigarette smokers mean COHb rose from 2·9% to 9·6% and plasma nicotine from 79·0 nmol/l to 281 nmol/l (12·8-45·6 ng/ml). This response was similar to that of cigarette smokers smoking cigarettes, which indicated that the subjects had inhaled and absorbed significant amounts of nicotine. In the primary pipe and cigar smokers the mean COHb rose from 0·8% to 1·0% and the plasma nicotine from 21 nmol/l to 32 nmol/l (3·4-5·2 ng/ml), indicating neither significant inhalation nor significant nicotine absorption. Since ex-cigarette smokers do not seem to lose their habit of inhaling when they change to cigars, measures aimed at persuading smokers to switch to cigars will have little effect on their health. Pipe and cigar smokers who have never smoked cigarettes do not inhale, which probably accounts for their reduced incidence of coronary heart disease and lung cancer. But they also appear not to absorb nicotine, which suggests that nicotine is absorbed largely from the lung and that the buccal mucosa is unimportant. It also raises the interesting question of why primary pipe and cigar smokers do smoke. PMID:589225

Determination of beryllium concentrations in UK ambient air

NASA Astrophysics Data System (ADS)

Goddard, Sharon L.; Brown, Richard J. C.; Ghatora, Baljit K.

2016-12-01

Air quality monitoring of ambient air is essential to minimise the exposure of the general population to toxic substances such as heavy metals, and thus the health risks associated with them. In the UK, ambient air is already monitored under the UK Heavy Metals Monitoring Network for a number of heavy metals, including nickel (Ni), arsenic (As), cadmium (Cd) and lead (Pb) to ensure compliance with legislative limits. However, the UK Expert Panel on Air Quality Standards (EPAQS) has highlighted a need to limit concentrations of beryllium (Be) in air, which is not currently monitored, because of its toxicity. The aim of this work was to analyse airborne particulate matter (PM) sampled onto filter papers from the UK Heavy Metals Monitoring Network for quantitative, trace level beryllium determination and compare the results to the guideline concentration specified by EPAQS. Samples were prepared by microwave acid digestion in a matrix of 2% sulphuric acid and 14% nitric acid, verified by the use of Certified Reference Materials (CRMs). The digested samples were then analysed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The filters from the UK Heavy Metals Monitoring Network were tested using this procedure and the average beryllium concentration across the network for the duration of the study period was 7.87 pg m-3. The highest site average concentration was 32.0 pg m-3 at Scunthorpe Low Santon, which is significantly lower than levels that are thought to cause harm. However the highest levels were observed at sites monitoring industrial point sources, indicating that beryllium is being used and emitted, albeit at very low levels, from these point sources. Comparison with other metals concentrations and data from the UK National Atmospheric Emissions Inventory suggests that current emissions of beryllium may be significantly overestimated.

The future of nicotine replacement.

PubMed

Russell, M A

1991-05-01

Following in the wake of progress forged by nicotine chewing gum, a new generation of nicotine replacement products will soon be available as aids to giving up smoking. These range from nicotine skin patches, which take 6-8 hrs to give very flat steady-state peak blood levels, to nicotine vapour inhalers which mimic the transient high-nicotine boli that follow within a few seconds of each inhaled puff of cigarette smoke. Other products undergoing clinical trials include a nasal nicotine spray and nicotine lozenges. It is argued here that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco that makes the virtual elimination of tobacco a realistic future target. Their relative safety compared with tobacco is discussed. A case is advanced for selected nicotine replacement products to be made as palatable and acceptable as possible and actively promoted on the open market to enable them to compete with tobacco products. They will also need health authority endorsement, tax advantages and support from the anti-smoking movement if tobacco use is to be gradually phased out altogether.

Nicotine blood levels and short-term smoking reduction with an electronic nicotine delivery system.

PubMed

Nides, Mitchell A; Leischow, Scott J; Bhatter, Meghna; Simmons, Michael

2014-03-01

To evaluate nicotine delivery from the NJOY® King Bold Electronic Nicotine Delivery System (ENDS) and its short-term potential for smoking reduction or cessation. One week of ad libitum use was followed by measurements of plasma nicotine, heart rate, and craving and withdrawal after 12 hours of nicotine abstinence in 25 adult smokers not interested in quitting. After 5 minutes of use, blood nicotine levels increased by a mean of 3.5 ng/mL (p < .001), heart rate increased, and craving was reduced by 55%. Cigarettes per day were reduced by 39% during the test week, and perceptions of use for reduction or cessation were positive. The NJOY® King Bold ENDS delivers nicotine and led to short-term smoking reduction.

Mechanisms of Nicotine Addiction

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGehee, Daniel

Nicotine reinforces the use of tobacco products primarily through its interaction with specific receptor proteins within the brain’s reward centers. A critical step in the process of addiction for many drugs, including nicotine, is the release of the neurotransmitter dopamine. A single nicotine exposure will enhance dopamine levels for hours, however, nicotinic receptors undergo both activation and then desensitization in minutes, which presents an important problem. How does the time course of receptor activity lead to the prolonged release of dopamine? We have found that persistent modulation of both inhibitory and excitatory synaptic connections by nicotine underlies the sustained increasemore » in dopamine release. Because these inputs express different types of nicotinic receptors there is a coordinated shift in the balance of synaptic inputs toward excitation of the dopamine neurons. Excitatory inputs are turned on while inhibitory inputs are depressed, thereby boosting the brain’s reward system.« less

Littered cigarette butts as a source of nicotine in urban waters

NASA Astrophysics Data System (ADS)

Roder Green, Amy L.; Putschew, Anke; Nehls, Thomas

2014-11-01

The effect of nicotine from littered cigarette butts on the quality of urban water resources has yet to be investigated. This two-part study addresses the spatial variation, seasonal dynamics and average residence time of littered cigarette butts in public space, as well as the release of nicotine from cigarette butts to run-off in urban areas during its residence time. Thereby, we tested two typical situations: release to standing water in a puddle and release during alternating rainfall and drying. The study took place in Berlin, Germany, a city which completely relies on its own water resources to meet its drinking water demand. Nine typical sites located in a central district, each divided into 20 plots were studied during five sampling periods between May 2012 and February 2013. The nicotine release from standardized cigarette butts prepared with a smoking machine was examined in batch and rainfall experiments. Littered cigarette butts are unevenly distributed among both sites and plots. The average butt concentration was 2.7 m-2 (SD = 0.6 m-2, N = 862); the maximum plot concentration was 48.8 butts m-2. This heterogeneity is caused by preferential littering (gastronomy, entrances, bus stops), redistribution processes such as litter removal (gastronomy, shop owners), and the increased accumulation in plots protected from mechanized street sweeping (tree pits, bicycle stands). No significant seasonal variation of cigarette butt accumulation was observed. On average, cigarette butt accumulation is characterized by a 6 days cadence due to the rhythm and effectiveness of street sweeping (mean weekly butt accumulation rate = 0.18 m-2 d-1; SD = 0.15 m-1). Once the butt is exposed to standing water, elution of nicotine occurs rapidly. Standardized butts released 7.3 mg g-1 nicotine in a batch experiment (equivalent to 2.5 mg L-1), 50% of which occurred within the first 27 min. In the rainfall experiment, the cumulative nicotine release from fifteen consecutive

Employee and customer handling of nicotine-containing e-liquids in vape shops.

PubMed

Garcia, Robert; Allem, Jon Patrick; Baezconde-Garbanati, Lourdes; Unger, Jennifer Beth; Sussman, Steve

2016-01-01

Vape shops sell electronic cigarettes and related products such as e-liquids, which may contain nicotine. Direct contact with nicotine can lead to adverse health effects, and few regulations exist on how nicotine is handled in vape shops. This study examined how customers and employees come into contact with, and handle, nicotine-containing e-liquids in vape shops with the goal of informing potential future regulation of nicotine handling in vape shops. Data were collected from 77 vape shops in the Los Angeles basin. Characteristics of the shops were documented by employee interviews and in store observations. Data collection was focused on shops located in areas with high concentrations of communities of interest; 20 shops from African-American communities, 17 from Hispanic communities, 18 from Korean communities, and 22 from non-Hispanic White communities. Half of the vape shops allowed customers to sample e-liquids with nicotine. Most of the shops (83%) provided self-service sampling stations for customers. A majority of shop employees (72%) reported that spills of e-liquids containing nicotine had occurred in the past. While 64% of the shops provided safety equipment, only 34% provided equipment for proper nicotine handling. Furthermore, 62% of shop employees reported handling nicotine without gloves or other safety equipment. Regulation on the handling of nicotine by customers and vape shop employees is important to prevent unsafe practices and subsequent injury. The frequent occurrence of spills and limited availability of safety equipment in vape shops highlights the need for the creation and enforcement of regulations to protect employees and customers. Appropriate safety training and equipment should be provided to employees to prevent accidental exposure to nicotine. Information on ways to safely handle nicotine should be communicated to vape shop employees and customers.

Employee and customer handling of nicotine-containing e-liquids in vape shops

PubMed Central

Garcia, Robert; Allem, Jon Patrick; Baezconde-Garbanati, Lourdes; Unger, Jennifer Beth; Sussman, Steve

2017-01-01

INTRODUCTION Vape shops sell electronic cigarettes and related products such as e-liquids, which may contain nicotine. Direct contact with nicotine can lead to adverse health effects, and few regulations exist on how nicotine is handled in vape shops. This study examined how customers and employees come into contact with, and handle, nicotine-containing e-liquids in vape shops with the goal of informing potential future regulation of nicotine handling in vape shops. METHODS Data were collected from 77 vape shops in the Los Angeles basin. Characteristics of the shops were documented by employee interviews and in store observations. Data collection was focused on shops located in areas with high concentrations of communities of interest; 20 shops from African-American communities, 17 from Hispanic communities, 18 from Korean communities, and 22 from non-Hispanic White communities. RESULTS Half of the vape shops allowed customers to sample e-liquids with nicotine. Most of the shops (83%) provided self-service sampling stations for customers. A majority of shop employees (72%) reported that spills of e-liquids containing nicotine had occurred in the past. While 64% of the shops provided safety equipment, only 34% provided equipment for proper nicotine handling. Furthermore, 62% of shop employees reported handling nicotine without gloves or other safety equipment. CONCLUSIONS Regulation on the handling of nicotine by customers and vape shop employees is important to prevent unsafe practices and subsequent injury. The frequent occurrence of spills and limited availability of safety equipment in vape shops highlights the need for the creation and enforcement of regulations to protect employees and customers. Appropriate safety training and equipment should be provided to employees to prevent accidental exposure to nicotine. Information on ways to safely handle nicotine should be communicated to vape shop employees and customers. PMID:28660255

Secondhand Tobacco Smoke: An Occupational Hazard for Smoking and Non-Smoking Bar and Nightclub Employees

PubMed Central

Jones, Miranda R; Wipfli, Heather; Shahrir, Shahida; Avila-Tang, Erika; Samet, Jonathan M; Breysse, Patrick N; Navas-Acien, Ana

2013-01-01

Background In the absence of comprehensive smoking bans in public places, bars and nightclubs have the highest concentrations of secondhand tobacco smoke, posing a serious health risk for workers in these venues. Objective To assess exposure of bar and nightclub employees to secondhand smoke, including non-smoking and smoking employees. Methods Between 2007 and 2009, we recruited approximately 10 venues per city and up to 5 employees per venue in 24 cities in the Americas, Eastern Europe, Asia and Africa. Air nicotine concentrations were measured for 7 days in 238 venues. To evaluate personal exposure to secondhand smoke, hair nicotine concentrations were also measured for 625 non-smoking and 311 smoking employees (N=936). Results Median (interquartile range [IQR]) air nicotine concentrations were 3.5 (1.5, 8.5) µg/m3 and 0.2 (0.1, 0.7) µg/m3 in smoking and smoke-free venues, respectively. Median (IQR) hair nicotine concentrations were 6.0 (1.6, 16.0) ng/mg and 1.7 (0.5, 5.5) ng/mg in smoking and non-smoking employees, respectively. After adjustment for age, sex, education, living with a smoker, hair treatment and region, a 2-fold increase in air nicotine concentrations was associated with a 30% (95% confidence interval 23%, 38%) increase in hair nicotine concentrations in non-smoking employees and with a 10% (2%, 19%) increase in smoking employees. Conclusions Occupational exposure to secondhand smoke, assessed by air nicotine, resulted in elevated concentrations of hair nicotine among non-smoking and smoking bar and nightclub employees. The high levels of airborne nicotine found in bars and nightclubs and the contribution of this exposure to employee hair nicotine concentrations support the need for legislation measures that ensure complete protection from secondhand smoke in these venues. PMID:22273689

Variability of air ion concentrations in urban Paris

NASA Astrophysics Data System (ADS)

Dos Santos, V. N.; Herrmann, E.; Manninen, H. E.; Hussein, T.; Hakala, J.; Nieminen, T.; Aalto, P. P.; Merkel, M.; Wiedensohler, A.; Kulmala, M.; Petäjä, T.; Hämeri, K.

2015-12-01

Air ion concentrations influence new particle formation and consequently the global aerosol as potential cloud condensation nuclei. We aimed to evaluate air ion concentrations and characteristics of new particle formation events (NPF) in the megacity of Paris, France, within the MEGAPOLI (Megacities: Emissions, urban, regional and Global Atmospheric Pollution and climate effects, and Integrated tools for assessment and mitigation) project. We measured air ion number size distributions (0.8-42 nm) with an air ion spectrometer and fine particle number concentrations (> 6 nm) with a twin differential mobility particle sizer in an urban site of Paris between 26 June 2009 and 4 October 2010. Air ions were size classified as small (0.8-2 nm), intermediate (2-7 nm), and large (7-20 nm). The median concentrations of small and large ions were 670 and 680 cm-3, respectively, (sum of positive and negative polarities), whereas the median concentration of intermediate ions was only 20 cm-3, as these ions were mostly present during new particle formation bursts, i.e. when gas-to-particle conversion produced fresh aerosol particles from gas phase precursors. During peaks in traffic-related particle number, the concentrations of small and intermediate ions decreased, whereas the concentrations of large ions increased. Seasonal variations affected the ion population differently, with respect to their size and polarity. NPF was observed in 13 % of the days, being most frequent in spring and late summer (April, May, July, and August). The results also suggest that NPF was favoured on the weekends in comparison to workdays, likely due to the lower levels of condensation sinks in the mornings of weekends (CS weekdays 09:00: 18 × 10-3 s-1; CS weekend 09:00: 8 × 10-3 s-1). The median growth rates (GR) of ions during the NPF events varied between 3 and 7 nm h-1, increasing with the ion size and being higher on workdays than on weekends for intermediate and large ions. The median GR of

Mephedrone and nicotine: oxidative stress and behavioral interactions in animal models.

PubMed

Budzynska, Barbara; Boguszewska-Czubara, Anna; Kruk-Slomka, Marta; Kurzepa, Jacek; Biala, Grazyna

2015-05-01

The purpose of our experiment was to examine the influence of co-administration of nicotine and mephedrone on anxiety-like behaviors, cognitive processes and the nicotine-induced behavioral sensitization as well as processes connected with induction of oxidative stress in the brain of male Swiss mice. The results revealed that co-administration of subthreshold doses of mephedrone and nicotine (0.05 mg/kg each) exerted marked anxiogenic profile in the elevated plus maze and displayed pro-cognitive action in the passive avoidance paradigm (nicotine 0.05 mg/kg and mephedrone 2.5 mg/kg). Furthermore, one of the main findings of the present study was that mephedrone, administered alone at the dose not affecting locomotor activity of mice (1 mg/kg), enhanced the expression of nicotine-induced locomotor sensitization. Moreover, mephedrone administered with nicotine decreased general antioxidant status and catalase activity as well as antioxidant enzymes activity in the hippocampus and prefrontal cortex and increased concentration of malondialdehyde, an indicator of lipid peroxidation processes. Considering the likelihood that mephedrone is taken as a part of polydrug combination with nicotine, the effects of this combination on mammalian organisms have been confirmed in our study. Understanding the consequences of co-administration of psychoactive substances on the central nervous system and oxidative processes in the brain provide the important toxicological significance, and may be useful in polydrug intoxication treatment.

[The effect of Toll-like receptor 4 in nicotine suppressing the osteogenic potential of periodontal ligament stem cells].

PubMed

Luan, Yan; Deqin, Yang

2017-08-01

Objective To explore the impact of nicotine on proliferation and osteogenic capability of periodontal ligament stem cells (PDLSCs), and the role of Toll-like receptor 4 (TLR4) in nicotine, suppressing the osteogenic capability of PDLSCs. Methods PDLSCs were cultured in vitro, and the flow cytometer was used to identify the surface antigen markers of PDLSCs. WST-1 was used to detect the proliferation ability of PDLSCs, which were stimulated by different concentrations of nicotine. Alizarin red staining was used to observe the formation of mineralized nodules after PDLSCs stimulation with different concentrations of nicotine. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to detect the change in osteogenic potential of PDLSCs stimulated by nicotine, after TAK-242, and with the inhibitor of TLR4. Results PDLSCs expressed mesenchymal stem cell-associated markers CD90 and CD105. When the concentration of nicotine was 10⁻⁴ mol·L⁻¹, the PDLSC proliferation could be suppressed after 3 d compared with the control group (P<0.05). The amount of mineralized nodules reduced after osteogenic differentiation at 21 d by alizarin red staining. RT-PCR and Western blot showed the expression levels of alkaline phosphatase (ALP), and osteocalcin (OCN), and the Runt-related transcription factor-2 (Runx-2) were lower than in the control group when nicotine suppressed the PDLSCs (P<0.05). This effect was attenuated after TAK-242 was added. Conclusion Nicotine suppresses the proliferation and osteogenic capability of PDLSCs, which may be regulated by TLR4.

Cholinergic nicotinic and muscarinic receptors in dementia of Alzheimer, Parkinson and Lewy body types.

PubMed

Perry, E K; Smith, C J; Court, J A; Perry, R H

1990-01-01

Cholinergic nicotinic and muscarinic receptor binding were measured in post mortem human brain tissue, using low (nM) concentrations of (3H)-nicotine to detect predominately the high affinity nicotinic site and (3H)-N-methylscopolamine in the presence and absence of 3 x 10(-4) M carbachol to measure both the low and high affinity agonist subtypes of the muscarinic receptor group. Consistent with most previous reports, the nicotinic but not muscarinic binding was reduced in the different forms of dementia associated with cortical cholinergic deficits, including Alzheimer's and Parkinson's disease, senile dementia of Lewy body type (SDLT) and Down's syndrome (over 50 years). Analysis of (3H)-nicotine binding displaced by a range of carbachol concentrations (10(-9)-10(-3) M) indicated 2 binding sites for nicotine and that the high affinity rather than low affinity site was reduced in Alzheimer's disease. In all 3 cortical areas investigated (temporal, parietal and occipital) there were increases in the low affinity muscarinic site in Parkinson's disease and SDLT but not Alzheimer's disease or middle-aged Down's syndrome. This observation raised the question of whether the presence of neurofibrillary tangles (evident in the latter but not former 2 disorders) is incompatible with denervation-induced muscarinic supersensitivity in cholinoceptive neurons which include cortical pyramids generally affeted by tangle formation.

Connections of nicotine to cancer.

PubMed

Grando, Sergei A

2014-06-01

This Opinion article discusses emerging evidence of direct contributions of nicotine to cancer onset and growth. The list of cancers reportedly connected to nicotine is expanding and presently includes small-cell and non-small-cell lung carcinomas, as well as head and neck, gastric, pancreatic, gallbladder, liver, colon, breast, cervical, urinary bladder and kidney cancers. The mutagenic and tumour-promoting activities of nicotine may result from its ability to damage the genome, disrupt cellular metabolic processes, and facilitate growth and spreading of transformed cells. The nicotinic acetylcholine receptors (nAChRs), which are activated by nicotine, can activate several signalling pathways that can have tumorigenic effects, and these receptors might be able to be targeted for cancer therapy or prevention. There is also growing evidence that the unique genetic makeup of an individual, such as polymorphisms in genes encoding nAChR subunits, might influence the susceptibility of that individual to the pathobiological effects of nicotine. The emerging knowledge about the carcinogenic mechanisms of nicotine action should be considered during the evaluation of regulations on nicotine product manufacturing, distribution and marketing.

Hydrothermal synthesis and processing of hydrogen titanate nanotubes for nicotine electrochemical sensing

NASA Astrophysics Data System (ADS)

Mersal, Gaber A. M.; Mostafa, Nasser Y.; Omar, Abd-Elkader H.

2017-08-01

Hydrogen titanate nanotubes (HTNT) were prepared via acid washing of hydrothermally synthesized sodium titantate nanotube. HTNTs with diameters in the range 7-9 nm and length of several hundred nanometers were annealed at different temperatures and used to modify carbon paste electrode (CPE). Cyclic and square wave voltammetric techniques were used to investigate the behavior of nicotine at HTNT modified carbon paste electrode (HTNTCPE). The nicotine-oxidation reaction over HTNTCPE was irreversible and adsorption process is the rate determining step. HTNTs annealed at 500 °C showed the best response to nicotine. The nicotine concentration was determined at the ideal conditions by square wave voltammetry (SWV). The calibration was linear from 0.1 to 500.0 µmol l-1 with a correlation coefficient of 0.995. The detection limits were found to be 0.005 µmol l-1. The present HTNTCPE was used to the determination of nicotine in two cigarette brands and it showed outstanding performance with respect to detection limit and sensitivity.

Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors.

PubMed

Yohn, Nicole L; Turner, Jill R; Blendy, Julie A

2014-05-01

Although nicotine mediates its effects through several nicotinic acetylcholine receptor (nAChR) subtypes, it remains to be determined which nAChR subtypes directly mediate heightened anxiety during withdrawal. Relative success in abstinence has been found with the nAChR partial agonist varenicline (Chantix; Pfizer, Groton, CT); however, treatment with this drug fails to alleviate anxiety in individuals during nicotine withdrawal. Therefore, it is hypothesized that success can be found by the repurposing of other nAChR partial agonists for cessation therapies that target anxiety. It is noteworthy that the selective partial agonists for α4β2, ABT-089 [2-methyl-3-[2(S)-pyrrolidinylmethoxy]pyridine], and α7, ABT-107 [5-(6-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy] pyridazin-3-yl)-1H-indole] (AbbVie, North Chicago, IL), have not been evaluated as possible therapeutics for nicotine cessation. Therefore, we examined the effect of ABT-089 and ABT-107 on anxiety during withdrawal from nicotine in the novelty-induced hypophagia (NIH) paradigm. We found that short-term administration of ABT-089 and ABT-107 alleviate anxiety-like behavior during withdrawal from nicotine while long-term administration of ABT-089 but not ABT-107 reduces anxiety-like behavior during withdrawal. After behavioral testing, brains were harvested and β2-containing nAChRs were measured using [(3)H]epibaditine. ABT-089 and ABT-107 do not upregulate nAChRs, which is in contrast to the upregulation of nAChRs observed after nicotine. Furthermore, ABT-089 is anxiogenic in nicotine naive animals, suggesting that the effects on anxiety are specifically related to the nicotine-dependent state. Together, these studies identify additional nAChR partial agonists that may aid in the rational development of smoking cessation aids.

Adsorption of nicotine from aqueous solution onto hydrophobic zeolite type USY

NASA Astrophysics Data System (ADS)

Lazarevic, Natasa; Adnadjevic, Borivoj; Jovanovic, Jelena

2011-07-01

The isothermal adsorption of nicotine from an aqueous solution onto zeolite type USY was investigated. The adsorption isotherms of nicotine onto the zeolite at different temperatures ranging from 298 to 322 K were determined. It was found that the adsorption isotherms can be described by the model of Freundlich adsorption isotherm. Based on the adsorption isotherms the changes of adsorption heat, free energy and entropy with adsorption degree were determined. The determined decrease of adsorption heat with adsorption degree can be explained by the presence of the adsorption centers of different energy and concentration on interface of zeolite-nicotine solution. It was found that the probability function of density distribution of the heat of adsorption (DDF) has exponential form. It was concluded that the possibility of fitting the adsorption isotherms of nicotine onto the zeolite by Freundlich adsorption isotherm was a direct consequence of that. The determined increase in entropy with the increase in adsorption degree can be explained with the change of phase state of adsorbed nicotine.

The Influence of Nicotine Dose and Nicotine Dose Expectancy on the Cognitive and Subjective Effects of Cigarette Smoking

PubMed Central

Juliano, Laura M.; Fucito, Lisa M.; Harrell, Paul T.

2013-01-01

This study investigated the independent and interactive effects of nicotine dose and nicotine dose expectancy on smoking outcomes using a 2 (given nicotine vs. placebo) × 2 (told nicotine vs. placebo) Balanced Placebo Design (BPD). Smokers (N = 148) completed the Rapid Visual Information Processing Task (RVIP) and measures of smoking urge, mood, and cigarette ratings (e.g., satisfying) after smoking a nicotine or placebo cigarette crossed with instructions that the cigarette contained either nicotine or no nicotine. Nicotine cigarettes (0.6 mg nicotine) produced better sustained attention performance than placebos as indicated by RVIP reaction time, hits, and sensitivity (A′). Nicotine cigarettes also produced better mood and greater rewarding subjective effects of the cigarettes on 11 of 11 dimensions compared to placebos. Nicotine instructions resulted in fewer RVIP false alarms, better mood, and greater rewarding subjective effects of the cigarettes on 9 of 11 dimensions compared to placebo instructions. Nicotine dose by nicotine dose expectancy interactions were also observed for urge and tension-anxiety, such that the dose expectancy manipulation produced differential effects only among those who smoked placebo cigarettes. In contrast a significant interaction for self-reported vigor-activity demonstrated that the dose expectancy manipulation produced effects only among those who smoked nicotine cigarettes. This study provides additional evidence that nicotine improves cognitive performance, and provides initial evidence that denicotinized cigarettes smoked under the guise that they contain nicotine influence cognitive performance, albeit with less robust effects than nicotine. These data may inform the development of expectancy-based interventions for tobacco dependence. PMID:21463067

Effects of chronic administration of nicotine on storage and synthesis of noradrenaline in rat brain

PubMed Central

Bhagat, B.

1970-01-01

1. Chronic administration of nicotine (0·5 mg/kg, subcutaneously four times a day, 5 days a week, for 6 weeks) did not affect the growth rate and water intake in rats. In these animals food intake was normal for the first 5 weeks, but was significantly increased during the sixth week of treatment. 2. Nicotine administration increased the blood pressure of rats from 120 mm Hg to 151 mm Hg. 3. The concentrations of endogenous noradrenaline, dopamine, 5-hydroxytryptamine and acetylcholine in the brain remained unaltered. However, chronic treatment with nicotine increased the turnover rate of noradrenaline. Initial accumulation of 3H-noradrenaline was also significantly increased. 4. It is concluded from these studies that changes in the turnover of cerebral noradrenaline caused by chronic administration rather than changes in the concentration of noradrenaline may be an important factor in nicotine-induced behavioural changes. PMID:5413293

Secondhand Smoke Exposure Among Women and Children: Evidence From 31 Countries

PubMed Central

Wipfli, Heather; Avila-Tang, Erika; Navas-Acien, Ana; Kim, Sungroul; Onicescu, Georgiana; Yuan, Jie; Breysse, Patrick; Samet, Jonathan M.

2008-01-01

Objectives. We sought to describe the range of exposure to secondhand smoke (SHS) among women and children living with smokers around the world and generate locally relevant data to motivate the development of tobacco control policies and interventions in developing countries. Methods. In 2006, we conducted a cross-sectional exposure survey to measure air nicotine concentrations in households and hair nicotine concentrations among nonsmoking women and children in convenience samples of 40 households in 31 countries. Results. Median air nicotine concentration was 17 times higher in households with smokers (0.18 μg/m3) compared with households without smokers (0.01 μg/m3). Air nicotine and hair nicotine concentrations in women and children increased with the number of smokers in the household. The dose–response relationship was steeper among children. Air nicotine concentrations increased an estimated 12.9 times (95% confidence interval=9.4, 17.6) in households allowing smoking inside compared with those prohibiting smoking inside. Conclusions. Our results indicate that women and children living with smokers are at increased risk of premature death and disease from exposure to SHS. Interventions to protect women and children from household SHS need to be strengthened. PMID:18309121

Nicotine cut-off value in human hair as a tool to distinguish active from passive smokers: A cross-sectional study in Japanese men.

PubMed

Tsuji, Masayoshi; Kanda, Hideyuki; Hayakawa, Takehito; Mori, Yayoi; Ito, Teruna; Hidaka, Tomoo; Kakamu, Takeyasu; Kumagai, Tomohiro; Osaki, Yoneatsu; Kawazoe, Miki; Sato, Sei; Fukushima, Tetsuhito

2017-07-19

Nicotine concentration in hair is a useful marker of tobacco exposure. Detection of nicotine in the hair of non-smokers indicates passive smoking. Accurate measurement of nicotine among active and passive smokers can help in smoking cessation programs or programs designed to prevent secondhand smoke exposure. To establish, using high-performance liquid chromatography-ultraviolet detection (HPLC/UV), a hair nicotine cut-off value to distinguish active from passive smokers. Hair samples were collected from randomly chosen Japanese men (n= 192) between 2009 and 2011. Nicotine and cotinine levels in hair were measured using HPLC/UV with column-switching. T-tests and chi-square tests were performed to compare active and passive smokers, while receiver operating characteristic curves were used to evaluate the effectiveness of the cut-off value. There were 69 active smokers and 123 passive smokers. The nicotine and cotinine concentrations in hair were significantly higher in active than in passive smokers (p< 0.01). The area under the curve for nicotine was 0.92. A hair nicotine cut-off value of 5.68 ng/mg, with a sensitivity of 94.2% and specificity of 87.0%, was identified as the optimal cut-off value for separating active from passive smokers. Nicotine and cotinine concentrations in hair clearly distinguished active from passive smokers.

Influence of cigarette filter ventilation on smokers' mouth level exposure to tar and nicotine.

PubMed

Caraway, John W; Ashley, Madeleine; Bowman, Sheri A; Chen, Peter; Errington, Graham; Prasad, Krishna; Nelson, Paul R; Shepperd, Christopher J; Fearon, Ian M

2017-12-01

Cigarette filter ventilation allows air to be drawn into the filter, diluting the cigarette smoke. Although machine smoking reveals that toxicant yields are reduced, it does not predict human yields. The objective of this study was to investigate the relationship between cigarette filter ventilation and mouth level exposure (MLE) to tar and nicotine in cigarette smokers. We collated and reviewed data from 11 studies across 9 countries, in studies performed between 2005 and 2013 which contained data on MLE from 156 products with filter ventilation between 0% and 87%. MLE among 7534 participants to tar and nicotine was estimated using the part-filter analysis method from spent filter tips. For each of the countries, MLE to tar and nicotine tended to decrease as filter ventilation increased. Across countries, per-cigarette MLE to tar and nicotine decreased as filter ventilation increased from 0% to 87%. Daily MLE to tar and nicotine also decreased across the range of increasing filter ventilation. These data suggest that on average smokers of highly ventilated cigarettes are exposed to lower amounts of nicotine and tar per cigarette and per day than smokers of cigarettes with lower levels of ventilation. Copyright © 2017 British American Tobacco. Published by Elsevier Inc. All rights reserved.

Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents.

PubMed

Moheimani, Roya S; Bhetraratana, May; Peters, Kacey M; Yang, Benjamin K; Yin, Fen; Gornbein, Jeffrey; Araujo, Jesus A; Middlekauff, Holly R

2017-09-20

Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non-nicotine constituents in e-cigarette emissions in causing these pathologies in otherwise healthy humans. Thirty-three healthy volunteers who were not current e-cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e-cigarette with nicotine, but not to the e-cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high-frequency component and the increases in the low-frequency component and the low-frequency to high-frequency ratio were significantly greater following exposure to the e-cigarette with nicotine compared with exposure to the e-cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures. The acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine, not to non-nicotine constituents in e-cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e-cigarette exposure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Maintain levels of nicotine but reduce other smoke constituents: a formula for ''less-hazardous'' cigarettes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, J.C.; Young, J.C.; Rickert, W.S.

Twenty-two volunteers who smoked more than 20 cigarettes with ''high'' nicotine yields (0.8 to 1.2 mg) per day participated in an 8-week study designed to test the hypothesis that smoking cigarettes with a constant level of nicotine but reduced deliveries of tar, carbon monoxide, and hydrogen cyanide leads to a decrease in smoke absorption. All subjects smoked their usual high-nicotine brand for the first 3 weeks (P1), and the absorption of smoke constituents was determined from levels of thiocyanate and cotinine in saliva and serum, levels of carbon monoxide in expired air, and levels of carboxyhemoglobin in the blood. Duringmore » the final 5 weeks (P2), the treatment group (16 subjects) switched to the ''light'' version of their usual brands (similar yields of nicotine but with reduced yields of tar, carbon monoxide, and hydrogen cyanide); the control group (6 subjects) smoked their usual brands for the duration of the study. Average levels of cotinine for the subjects who switched during P2 were not significantly different from those of the control group as was expected. Slight reductions were noted in average expired-air carbon monoxide levels, blood carboxyhemoglobin, and saliva thiocyanate, but these reductions were smaller than anticipated based on brand characteristics. The results suggest that the ratio of smoke constituents is different when individuals, rather than machines, smoke cigarettes. Yields determined under subject-defined conditions are necessary in order to properly evaluate the role of nicotine in the design of ''less-hazardous'' cigarettes.« less

Effects of caffeine on persistence and reinstatement of nicotine-seeking behavior in rats: interaction with nicotine-associated cues

PubMed Central

Jernigan, Courtney

2013-01-01

Rationale Caffeine and nicotine are the most commonly co-used psychostimulants. However, it is still unclear whether caffeine exposure enhances nicotine-seeking behavior. Objective The present study examined the effects of caffeine on nicotine-seeking in rats trained to self-administer nicotine with and without presession administration of caffeine. Methods Male Sprague–Dawley rats were trained to intravenously self-administer nicotine (0.03 mg/kg/infusion, freebase) on a fixed ratio 5 schedule of reinforcement and associate a stimulus cue with each nicotine administration. Five minutes before the sessions, the rats received an intraperitoneal administration of caffeine (5 mg/kg). Extinction tests were conducted under four conditions: presession caffeine administration, response-contingent presentation of nicotine cues, neither condition, or both conditions. Reinstatement tests were conducted after responding was extinguished by withholding presession caffeine, nicotine, and its cues. A separate group of rats trained without presession caffeine exposure was also subjected to the reinstatement tests. Results In the rats trained with presession caffeine exposure, continued caffeine administration sustained nicotine-seeking responses and interacted with nicotine cues to significantly delay the extinction of nicotine-seeking behavior. Readministration of caffeine after extinction effectively reinstated nicotine-seeking behavior. In caffeine-naive rats, caffeine administration did not reinstate extinguished nicotine-seeking behavior but significantly potentiated the cue-induced reinstatement of nicotine-seeking. Conclusion These data demonstrate that caffeine administration sustained and reinstated nicotine-seeking behavior, possibly via its acquired discriminative-stimulus properties predictive of nicotine availability. These findings suggest that smokers who attempt to quit may benefit from stopping caffeine consumption. PMID:21947355

40 CFR Appendix IV to Part 266 - Reference Air Concentrations*

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Reference Air Concentrations* IV Appendix IV to Part 266 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... MANAGEMENT FACILITIES Pt. 266, App. IV Appendix IV to Part 266—Reference Air Concentrations* Constituent CAS...

40 CFR Appendix IV to Part 266 - Reference Air Concentrations*

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Reference Air Concentrations* IV Appendix IV to Part 266 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... MANAGEMENT FACILITIES Pt. 266, App. IV Appendix IV to Part 266—Reference Air Concentrations* Constituent CAS...

40 CFR Appendix IV to Part 266 - Reference Air Concentrations*

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Reference Air Concentrations* IV Appendix IV to Part 266 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... MANAGEMENT FACILITIES Pt. 266, App. IV Appendix IV to Part 266—Reference Air Concentrations* Constituent CAS...

40 CFR Appendix IV to Part 266 - Reference Air Concentrations*

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Reference Air Concentrations* IV Appendix IV to Part 266 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... MANAGEMENT FACILITIES Pt. 266, App. IV Appendix IV to Part 266—Reference Air Concentrations* Constituent CAS...

Validation of the human odor span task: effects of nicotine.

PubMed

MacQueen, David A; Drobes, David J

2017-10-01

Amongst non-smokers, nicotine generally enhances performance on tasks of attention, with limited effect on working memory. In contrast, nicotine has been shown to produce robust enhancements of working memory in non-humans. To address this gap, the present study investigated the effects of nicotine on the performance of non-smokers on a cognitive battery which included a working memory task reverse-translated from use with rodents (the odor span task, OST). Nicotine has been reported to enhance OST performance in rats and the present study assessed whether this effect generalizes to human performance. Thirty non-smokers were tested on three occasions after consuming either placebo, 2 mg, or 4 mg nicotine gum. On each occasion, participants completed a battery of clinical and experimental tasks of working memory and attention. Nicotine was associated with dose-dependent enhancements in sustained attention, as evidenced by increased hit accuracy on the rapid visual information processing (RVIP) task. However, nicotine failed to produce main effects on OST performance or on alternative measures of working memory (digit span, spatial span, letter-number sequencing, 2-back) or attention (digits forward, 0-back). Interestingly, enhancement of RVIP performance occurred concomitant to significant reductions in self-reported attention/concentration. Human OST performance was significantly related to N-back performance, and as in rodents, OST accuracy declined with increasing memory load. Given the similarity of human and rodent OST performance under baseline conditions and the strong association between OST and visual 0-back accuracy, the OST may be particular useful in the study of conditions characterized by inattention.

Voluntary Co-Consumption of Alcohol and Nicotine: Effects of Abstinence, Intermittency, and Withdrawal in Mice

PubMed Central

O’Rourke, Kyu Y.; Touchette, Jillienne C.; Hartell, Elizabeth C.; Bade, Elizabeth J.; Lee, Anna M.

2018-01-01

Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction. PMID:27342124

Optical methods in modeling nicotine effect on the surface water of cell membranes

NASA Astrophysics Data System (ADS)

Alexandrova, Tatyana V.; Rogacheva, Svetlana M.; Kuznetsov, Pavel E.; Gubina, Tamara I.

2005-06-01

Fluorescence and spectrophotometric methods have been used for investigation of nicotine action on the state and mobility of the surface water. The surfaces of membranes and proteins were simulated with the help of liposomes and ultradispersive diamonds consequently. Nicotine was shown to reduce the stability of liposomes and to change the aggregative ability of ultradispersive diamonds. The wave-like curves for the nicotine concentration dependences of the pointed features were observed. Such shape of responses was suggested to be due to the changing in structure and dynamics of water hydrogen bonds net near the surface of the model systems induced by nicotine molecules. The surface water phase was supposed to be one of signal elements ofthe ligand receptor recognition process.

Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy.

PubMed

Grebenstein, Patricia E; Burroughs, Danielle; Roiko, Samuel A; Pentel, Paul R; LeSage, Mark G

2015-06-01

The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. The present study examined these issues in a rodent nicotine self-administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy*

PubMed Central

Grebenstein, Patricia E.; Burroughs, Danielle; Roiko, Samuel A.; Pentel, Paul R.; LeSage, Mark G.

2015-01-01

Background The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. Methods The present study examined these issues in a rodent nicotine self- administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Results Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. Conclusions These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. PMID:25891231

Nicotine and Anatabine Exposure from Very Low Nicotine Content Cigarettes

PubMed Central

Denlinger, Rachel L.; Smith, Tracy T.; Murphy, Sharon E.; Koopmeiners, Joseph S.; Benowitz, Neal L.; Hatsukami, Dorothy K.; Pacek, Lauren R.; Colino, Cirielle; Cwalina, Samantha N.; Donny, Eric C.

2018-01-01

Objectives Research using very low nicotine content (VLNC) cigarettes has shown that participants underreport use of non-study cigarettes. Biomarkers of nicotine exposure could be used to verify compliance with VLNC cigarettes. This study aimed to characterize biomarkers of exposure when participants exclusively use VLNC cigarettes. Methods 23 participants stayed in a hotel that permitted smoking for 5 days and 4 nights. They were provided 2 packs of VLNC cigarettes each day (0.4 mg of nicotine/g of tobacco; Spectrum cigarettes) and did not have access to other tobacco products. 24-hour urine samples were collected to assess exposure to nicotine and anatabine. Results After 4 days of exclusive use, the geometric means for urinary total cotinine, total nicotine equivalents (TNE), and anatabine were 1.13 nmol/ml (92% reduction), 3.17 nmol/ml (94% reduction) and 0.0031 nmol/ml (93% reduction). The population estimates of the 95th percentile of cotinine, TNE, and anatabine levels were 2.69, 6.41, and 0.0099 nmol/ml, respectively. Conclusions Study participants exclusively smoking 0.4 mg/g Spectrum cigarettes are unlikely to have biomarker values above these levels. The data presented here will be valuable to researchers conducting research on use of VLNC cigarettes. PMID:29600258

Nicotinic Cholinergic Synaptic Mechanisms in the Ventral Tegmental Area Contribute to Nicotine Addiction

ERIC Educational Resources Information Center

Pidoplichko, Volodymyr I.; Noguchi, Jun; Areola, Oluwasanmi O.; Liang, Yong; Peterson, Jayms; Zhang, Tianxiang; Dani, John A.

2004-01-01

Tobacco use is a major health problem that is estimated to cause 4 million deaths a year worldwide. Nicotine is the main addictive component of tobacco. It acts as an agonist to activate and desensitize nicotinic acetylcholine receptors (nAChRs). A component of nicotine's addictive power is attributable to actions on the mesolimbic dopaminergic…

The Air Force concentrating photovoltaic array program

NASA Technical Reports Server (NTRS)

Geis, Jack W.

1987-01-01

A summary is given of Air Force solar concentrator projects beginning with the Rockwell International study program in 1977. The Satellite Materials Hardening Programs (SMATH) explored and developed techniques for hardening planar solar cell array power systems to the combined nuclear and laser radiation threat environments. A portion of program dollars was devoted to developing a preliminary design for a hardened solar concentrator. The results of the Survivable Concentrating Photovoltaic Array (SCOPA) program, and the design, fabrication and flight qualification of a hardened concentrator panel are discussed.

The effects of nicotine on ethanol-induced conditioned taste aversions in Long-Evans rats.

PubMed

Rinker, Jennifer A; Busse, Gregory D; Roma, Peter G; Chen, Scott A; Barr, Christina S; Riley, Anthony L

2008-04-01

Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use. Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine's impact on ethanol's aversive effects within a conditioned taste aversion design. Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine's effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined. Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination. These data demonstrate that nicotine may interact with ethanol, increasing ethanol's aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol's rewarding effects.

Simultaneous measurement of urinary total nicotine and cotinine as biomarkers of active and passive smoking among Japanese individuals.

PubMed

Matsumoto, Akiko; Matsumoto, Akane; Ichiba, Masayoshi; Payton, Nicole M; Oishi, Hirotaka; Hara, Megumi

2013-05-01

Measuring urinary cotinine is a popular and established method of biologically monitoring exposure to tobacco smoke. However, the lower detection limit of cotinine often impedes the evaluation of passive (second-hand) smoking and this, together with unconverted nicotine, does not reflect actual levels of exposure. Furthermore, a portion of the Japanese population might have decreased ability to metabolize nicotine. The present study was therefore carried out to validate the simultaneous analysis of total concentrations of free nicotine and cotinine and their glucuronides to determine actual levels of voluntary and involuntary exposure to cigarette smoke. Urine samples from 118 Japanese smokers and 117 non-smokers were analyzed using gas chromatography-mass spectrometry. Voluntary and involuntary smoking status was self-reported and workplace smoking restrictions were objectively evaluated. The integrated sum of all concentrations showed 2.2- and 2.4-fold higher total levels (free and glucuronide) of nicotine and cotinine relative to the free levels. Median (quartiles) of total nicotine and cotinine were 1635 (2222) and 3948 (3512) ng/mL in smokers, and 3.5 (5.3) and 2.8 (4.2) ng/mL in non-smokers. Concentrations of urinary nicotine were higher than those of cotinine in 21 % of smokers and in 54 % of non-smokers. Nicotine and cotinine levels were significantly associated with a smoking habit, as well as being significantly associated with the workplace and home environments of non-smokers. The present method can monitor voluntary and involuntary exposure to tobacco smoke. Measuring total urinary nicotine levels might be useful for analyzing exposure to cigarette smoke among non-smokers.

Coexistence of passive and proton antiporter-mediated processes in nicotine transport at the mouse blood-brain barrier.

PubMed

Cisternino, Salvatore; Chapy, Hélène; André, Pascal; Smirnova, Maria; Debray, Marcel; Scherrmann, Jean-Michel

2013-04-01

Nicotine, the main tobacco alkaloid leading to smoking dependence, rapidly crosses the blood-brain barrier (BBB) to become concentrated in the brain. Recently, it has been shown that nicotine interacts with some organic cation transporters (OCT), but their influence at the BBB has not yet been assessed in vivo. In this study, we characterized the transport of nicotine at the mouse luminal BBB by in situ brain perfusion. Its influx was saturable and followed the Michaelis-Menten kinetics (K(m)=2.60 mM, V(max)=37.60 nmol/s/g at pH 7.40). At its usual micromolar concentrations in the plasma, most (79%) of the net transport of nicotine at the BBB was carrier-mediated, while passive diffusion accounted for 21%. Studies on knockout mice showed that the OCT Oct1-3, P-gp, and Bcrp did not alter [(3)H]-nicotine transport at the BBB. Neither did inhibiting the transporters Mate1, Octn, or Pmat. The in vivo manipulation of intracellular and/or extracellular pH, the chemical inhibition profile, and the trans-stimulation experiments demonstrated that the nicotine transporter at the BBB shared the properties of the clonidine/proton antiporter. The molecular features of this proton-coupled antiporter have not yet been identified, but it also transports diphenhydramine and tramadol and helps nicotine cross the BBB at a faster rate and to a greater extent. The pharmacological inhibition of this nicotine/proton antiporter could represent a new strategy to reduce nicotine uptake by the brain and thus help curb addiction to smoking.

Donepezil, an acetylcholinesterase inhibitor, attenuates nicotine self-administration and reinstatement of nicotine seeking in rats

PubMed Central

Kimmey, Blake A.; Rupprecht, Laura E.; Hayes, Matthew R.; Schmidt, Heath D.

2013-01-01

Nicotine craving and cognitive impairments represent core symptoms of nicotine withdrawal and predict relapse in abstinent smokers. Current smoking cessation pharmacotherapies have limited efficacy in preventing relapse and maintaining abstinence during withdrawal. Donepezil is an acetylcholinesterase inhibitor that has been shown previously to improve cognition in healthy non–treatment-seeking smokers. However, there are no studies examining the effects of donepezil on nicotine self-administration and/or the reinstatement of nicotine-seeking behavior in rodents. The present experiments were designed to determine the effects of acute donepezil administration on nicotine taking and the reinstatement of nicotine-seeking behavior, an animal model of relapse in abstinent human smokers. Moreover, the effects of acute donepezil administration on sucrose self-administration and sucrose seeking were also investigated in order to determine whether donepezil's effects generalized to other reinforced behaviors. Acute donepezil administration (1.0 or 3.0 mg/kg, i.p.) attenuated nicotine, but not sucrose self-administration maintained on a fixed-ratio 5 schedule of reinforcement. Donepezil administration also dose-dependently attenuated the reinstatement of both nicotine- and sucrose-seeking behaviors. Commonly reported adverse effects of donepezil treatment in humans are nausea and vomiting. However, at doses required to attenuate nicotine self-administration in rodents, no effects of donepezil on nausea/malaise as measured by pica were observed. Collectively, these results indicate that increased extracellular acetylcholine levels are sufficient to attenuate nicotine taking and seeking in rats and that these effects are not due to adverse malaise symptoms such as nausea. PMID:23231479

Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers.

PubMed

Heishman, S J; Henningfield, J E

2000-10-01

When administered acutely to nonsmokers, nicotine's effects on performance are inconsistent, perhaps because of suboptimal dosing or initial dysphoria that could interfere with performance. The purpose of this study was to determine if a range of nicotine doses administered for 8 days to nonsmokers would enhance psychomotor and cognitive abilities and to document the development of nicotine tolerance or sensitization. Twelve male volunteers, who reported ever smoking five cigarettes or less, participated in 8 consecutive experimental days in which they were administered four doses of nicotine polacrilex gum each day in this order: 0, 2, 4, and 8 mg. Performance, subjective, and physiological measures were assessed before and after each dose. Plasma nicotine concentration ranged from 6.9 to 11.5 ng/ml following the 8 mg dose. Nicotine increased rate of responding and decreased response time on working memory (digit recall); however, accuracy was impaired. Nicotine also decreased accuracy on visual scanning and attention (two-letter search), and the 8 mg dose impaired gross motor coordination (circular lights). Tolerance did not develop to the performance impairing effects of nicotine. Nicotine produced dose-related increases in ratings of dysphoria and negative mood, including tension, anxiety, nervousness, turning of stomach, and sedation. Tolerance developed to some, but not all, of these aversive effects. Tolerance also was not observed to the increased cardiovascular measures. Although tolerance developed to some of the aversive effects of nicotine, performance enhancement was not observed. These data do not support the hypothesis that nicotine-induced performance enhancement contributes to the reinforcing effects of tobacco use during the early stages of dependence development.

Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES✩

PubMed Central

Weltzin, Maegan M; Huang, Yanzhou; Schulte, Marvin K

2013-01-01

A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands. PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5–10 mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2+/beta2− interface and is dependent on residue beta2D218. HEPES did not potentiate low-sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors. PMID:22732654

Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES.

PubMed

Weltzin, Maegan M; Huang, Yanzhou; Schulte, Marvin K

2014-06-05

A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands. PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5-10mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2+/beta2- interface and is dependent on residue beta2D218. HEPES did not potentiate low-sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

CONCENTRATIONS OF TOXIC AIR POLLUTANTS IN THE U.S. SIMULATED BY AN AIR QUALITY MODEL

EPA Science Inventory

As part of the US National Air Toxics Assessment, we have applied the Community Multiscale Air Quality Model, CMAQ, to study the concentrations of twenty gas-phase, toxic, hazardous air pollutants (HAPs) in the atmosphere over the continental United States. We modified the Carbo...

Influence of experimental history on nicotine self-administration in squirrel monkeys.

PubMed

Desai, Rajeev I; Sullivan, Katherine A; Kohut, Stephen J; Bergman, Jack

2016-06-01

Methods for establishing robust long-term self-administration of intravenous (i.v.) nicotine, the primary psychoactive agent in tobacco, are not well-established in laboratory animals. Here, we examine the use of a fading procedure to establish robust and consistent i.v. nicotine self-administration under second-order schedule conditions in squirrel monkeys. First, self-administration behavior was developed in two groups of male squirrel monkeys using a second-order fixed-interval 5-min schedule with fixed-ratio 5 units (FI 5-min (FR5: S)). Comparable performances were maintained by i.v. cocaine (0.032 mg/kg/injection (inj); group A, n = 3) and the combination of food delivery (20-30 % condensed milk) and 0.01 mg/kg/inj i.v. nicotine (group B, n = 3). Subsequently, the concentration of condensed milk was gradually reduced to zero in the second group and self-administration behavior was maintained by i.v. nicotine alone. Next, self-administration of a range of doses of i.v. nicotine (0.001-0.032 mg/kg/inj) and, in additional experiments, the minor tobacco alkaloid anatabine (0.01-0.18 mg/kg/inj) was studied in both groups. Results show that nicotine and anatabine had reinforcing effects in both groups. However, optimal doses of nicotine and anatabine maintained significantly higher rates of i.v. self-administration behavior in subjects trained with the fading procedure than in subjects provided with a history of cocaine-maintained responding. These results illustrate conditions under which robust i.v. nicotine self-administration can be established in squirrel monkeys and the influence of prior experimental history in the expression of reinforcing effects of nicotine and anatabine.

Sex differences in nicotine preference.

PubMed

Pogun, Sakire; Yararbas, Gorkem; Nesil, Tanseli; Kanit, Lutfiye

2017-01-02

Smoking is the major cause of preventable deaths worldwide, and although there is a decline in overall smoking prevalence in developed countries, the decline in women is less pronounced than in men. Women become dependent faster and experience greater difficulties in quitting. Similar trends have been observed in animal models of nicotine/tobacco addiction. Individual differences in vulnerability to drug abuse are also observed in nicotine/tobacco addiction and point to the importance of sex differences. This Review, summarizes findings from three experimental approaches used to depict nicotine preference in animal models, intravenous and oral nicotine self-administration and nicotine-induced conditioned place preference. Nicotine preference is considered to be reflected in the animal's motivation to administer the drug (intravenously or orally) or to prefer an environment paired with the presence of the drug (conditioned place preference). These approaches all point to the importance of sex and age of the subjects; the preference of females and adolescents appear to be more pronounced than that of males and adults, respectively. A closer look at these factors will help us understand the mechanisms that underlie nicotine addiction and develop strategies to cope. Ignoring sex differences and reaching conclusions based only on studies using male subjects has resulted in erroneous generalizations in the past. Sex differences in nicotine preference have been clearly documented, and awareness on this aspect of nicotine dependence will significantly impact our success in translational research. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genetics of Nicotine Dependence and Pharmacotherapy

PubMed Central

Lessov-Schlaggar, Christina N.; Pergadia, Michele L.; Khroyan, Taline V.; Swan, Gary E.

2008-01-01

Nicotine dependence is substantially heritable. Several regions across the genome have been implicated in containing genes that confer liability to nicotine dependence and variation in individual genes has been associated with nicotine dependence. Smoking cessation measures are also heritable, and measured genetic variation is associated with nicotine dependence treatment efficacy. Despite significant strides in the understanding of the relative contribution of genetic and environmental factors to nicotine dependence and treatment, emergent challenges necessitate interdisciplinary coordinated effort for effective problem solving. These challenges include refinement of the nicotine dependence phenotype, better understanding of the dynamic interplay between genes and environment in nicotine dependence etiology, application and development of molecular and statistical methodology that can adequately address vast amounts of data, and continuous translational cross-talk. PMID:17888884

Wipe sampling for nicotine as a marker of thirdhand tobacco smoke contamination on surfaces in homes, cars, and hotels.

PubMed

Quintana, Penelope J E; Matt, Georg E; Chatfield, Dale; Zakarian, Joy M; Fortmann, Addie L; Hoh, Eunha

2013-09-01

Secondhand smoke contains a mixture of pollutants that can persist in air, dust, and on surfaces for months or longer. This persistent residue is known as thirdhand smoke (THS). Here, we detail a simple method of wipe sampling for nicotine as a marker of accumulated THS on surfaces. We analyzed findings from 5 real-world studies to investigate the performance of wipe sampling for nicotine on surfaces in homes, cars, and hotels in relation to smoking behavior and smoking restrictions. The intraclass correlation coefficient for side-by-side samples was 0.91 (95% CI: 0.87-0.94). Wipe sampling for nicotine reliably distinguished between private homes, private cars, rental cars, and hotels with and without smoking bans and was significantly positively correlated with other measures of tobacco smoke contamination such as air and dust nicotine. The sensitivity and specificity of possible threshold values (0.1, 1, and 10 μg/m(2)) were evaluated for distinguishing between nonsmoking and smoking environments. Sensitivity was highest at a threshold of 0.1 μg/m(2), with 74%-100% of smoker environments showing nicotine levels above threshold. Specificity was highest at a threshold of 10 μg/m(2), with 81%-100% of nonsmoker environments showing nicotine levels below threshold. The optimal threshold will depend on the desired balance of sensitivity and specificity and on the types of smoking and nonsmoking environments. Surface wipe sampling for nicotine is a reliable, valid, and relatively simple collection method to quantify THS contamination on surfaces across a wide range of field settings and to distinguish between nonsmoking and smoking environments.

Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers.

PubMed

Schober, Wolfgang; Szendrei, Katalin; Matzen, Wolfgang; Osiander-Fuchs, Helga; Heitmann, Dieter; Schettgen, Thomas; Jörres, Rudolf A; Fromme, Hermann

2014-07-01

Despite the recent popularity of e-cigarettes, to date only limited data is available on their safety for both users and secondhand smokers. The present study reports a comprehensive inner and outer exposure assessment of e-cigarette emissions in terms of particulate matter (PM), particle number concentrations (PNC), volatile organic compounds (VOC), polycyclic aromatic hydrocarbons (PAH), carbonyls, and metals. In six vaping sessions nine volunteers consumed e-cigarettes with and without nicotine in a thoroughly ventilated room for two hours. We analyzed the levels of e-cigarette pollutants in indoor air and monitored effects on FeNO release and urinary metabolite profile of the subjects. For comparison, the components of the e-cigarette solutions (liquids) were additionally analyzed. During the vaping sessions substantial amounts of 1,2-propanediol, glycerine and nicotine were found in the gas-phase, as well as high concentrations of PM2.5 (mean 197 μg/m(3)). The concentration of putative carcinogenic PAH in indoor air increased by 20% to 147 ng/m(3), and aluminum showed a 2.4-fold increase. PNC ranged from 48,620 to 88,386 particles/cm(3) (median), with peaks at diameters 24-36 nm. FeNO increased in 7 of 9 individuals. The nicotine content of the liquids varied and was 1.2-fold higher than claimed by the manufacturer. Our data confirm that e-cigarettes are not emission-free and their pollutants could be of health concern for users and secondhand smokers. In particular, ultrafine particles formed from supersaturated 1,2-propanediol vapor can be deposited in the lung, and aerosolized nicotine seems capable of increasing the release of the inflammatory signaling molecule NO upon inhalation. In view of consumer safety, e-cigarettes and nicotine liquids should be officially regulated and labeled with appropriate warnings of potential health effects, particularly of toxicity risk in children. Copyright © 2013 Elsevier GmbH. All rights reserved.

Effects of nicotine on corneal wound healing following acute alkali burn.

PubMed

Kim, Jong Won; Lim, Chae Woong; Kim, Bumseok

2017-01-01

Epidemiological studies have indicated that smoking is a pivotal risk factor for the progression of several chronic diseases. Nicotine, the addictive component of cigarettes, has powerful pathophysiological properties in the body. Although the effects of cigarette smoking on corneal re-epithelialization have been studied, the effects of nicotine on corneal wound healing-related neovascularization and fibrosis have not been fully demonstrated. The aim of this study was to evaluate the effects of chronic administration of nicotine on corneal wound healing following acute insult induced by an alkali burn. BALB/C female mice randomly received either vehicle (2% saccharin) or nicotine (100 or 200 μg/ml in 2% saccharin) in drinking water ad libitum. After 1 week, animals were re-randomized and the experimental group was subjected to a corneal alkali burn, and then nicotine was administered until day 14 after the alkali burn. A corneal alkali burn model was generated by placing a piece of 2 mm-diameter filter paper soaked in 1N NaOH on the right eye. Histopathological analysis and the expression level of the pro-angiogenic genes vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9) revealed that chronic nicotine administration enhanced alkali burn-induced corneal neovascularization. Furthermore, the mRNA expression of the pro-fibrogenic factors α-smooth muscle actin (αSMA), transforming growth factor-β (TGF-β), and collagen α1 (Col1) was enhanced in the high-concentration nicotine-treated group compared with the vehicle group after corneal injury. Immunohistochemical analysis also showed that the αSMA-positive area was increased in chronic nicotine-treated mice after corneal alkali burn. An in vitro assay found that expression of the α3, α7, and β1 nicotinic acetylcholine receptor (nAChR) subunits was significantly increased by chemical injury in human corneal fibroblast cells. Moreover, alkali-induced fibrogenic gene expression and

The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.

PubMed

McClernon, Francis Joseph; Froeliger, Brett; Rose, Jed E; Kozink, Rachel V; Addicott, Merideth A; Sweitzer, Maggie M; Westman, Eric C; Van Wert, Dana M

2016-07-01

Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy. © 2015 Society for the Study of Addiction.

The relationship between the nicotine metabolite ratio and three self-report measures of nicotine dependence across sex and race.

PubMed

Schnoll, Robert A; George, Tony P; Hawk, Larry; Cinciripini, Paul; Wileyto, Paul; Tyndale, Rachel F

2014-06-01

Variability in the rate of nicotine metabolism, measured by the nicotine metabolite ratio (NMR), is associated with smoking behavior. However, data linking the NMR with nicotine dependence measured by the Fagerström test for nicotine dependence (FTND) are mixed. Few past studies have examined alternative measures of nicotine dependence and how this relationship may vary by sex and race. Using data from smokers undergoing eligibility evaluation for a smoking cessation clinical trial (n = 833), this study examined variability in the relationship between NMR and nicotine dependence across sex and race and using three measures of nicotine dependence: FTND, time-to-first-cigarette (TTFC), and the heaviness of smoking index (HSI). Controlling for sex and race, nicotine metabolism was associated with nicotine dependence only when using the HSI (p < 0.05). Male normal metabolizers of nicotine were more likely to have high nicotine dependence based on the FTND and HSI (p < 0.05), but NMR was not related to measures of nicotine dependence in women. For African Americans, the NMR was associated with nicotine dependence only for the TTFC (p < 0.05), but NMR was not associated with nicotine dependence among Caucasians. Post hoc analyses indicated that the NMR was associated with cigarettes per day, overall, and among men and Caucasians (p < 0.05). While there was some variation in the relationship between nicotine metabolism and nicotine dependence across measures and sex and race, the results indicate that this relationship may be more attributable to the association between NMR and cigarettes per day.

Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

PubMed

Sudakov, S K; Bogdanova, N G

2016-10-01

The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

Interactions between acetylcholine, 5-hydroxytryptamine, nicotine and morphine on isolated rabbit atria

PubMed Central

Chittal, S. M.; Dadkar, N. K.; Gaitondé, B. B.

1968-01-01

1. The effects of 5-hydroxytryptamine (5-HT) and morphine on the responses to acetylcholine and nicotine of isolated rabbit atria were studied. 2. 5-Hydroxytryptamine (10 μg/ml.) and morphine (20 μg/ml.) blocked the negative chronotropic and inotropic actions of acetylcholine. 3. Nicotine (20 μg/ml.) produced stimulation of the atria, which was blocked by dichlorisoprenaline, morphine, 5-HT, bretylium and hemicholinium. Hemicholinium block was reversed by choline. 4. In reserpinized preparations, nicotine produced inhibition of atria and this action was also blocked by atropine, 5-HT and morphine. Inhibition induced by nicotine was potentiated by physostigmine. 5. 5-Hydroxytryptamine (20 μg/ml.) produced stimulation of atria. This was blocked by bretylium and reduced by hemicholinium. Hemicholinium block was reversed by choline. 6. It is concluded that 5-HT in low concentrations acts as a weak agonist at the cholinoceptive receptors and therefore blocks the action of acetylcholine. Furthermore, nicotine and larger doses of 5-HT have actions on ganglionic structures and liberate acetylcholine, which in turn releases catecholamines. PMID:4386371

Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soeda, Junpei; Morgan, Maelle; McKee, Chad

Highlights: Black-Right-Pointing-Pointer Cigarette smoke may induce liver fibrosis via nicotine receptors. Black-Right-Pointing-Pointer Nicotine induces proliferation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Nicotine activates hepatic fibrogenic pathways. Black-Right-Pointing-Pointer Nicotine receptor antagonists attenuate HSC proliferation. Black-Right-Pointing-Pointer Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine - which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells inmore » the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed - RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-{alpha}2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-{beta}1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type ({alpha}1, {beta}1, delta and epsilon) and neuronal type ({alpha}3, {alpha}6, {alpha}7, {beta}2 and {beta}4) nAChR subunits at the mRNA level. Among these subunits, {alpha}3, {alpha}7, {beta}1 and {epsilon} were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-{alpha}2 and TGF-{beta}1 mRNA expression were significantly upregulated by nicotine and inhibited by

Nicotine vaccines to treat tobacco dependence

PubMed Central

Goniewicz, Maciej L.; Delijewski, Marcin

2013-01-01

Tobacco smoking is globally far more widespread than use of any other substance of abuse. Nicotine is an important tobacco constituent that is responsible for addictive properties of smoking. The currently available medications for the treatment of nicotine addiction have limited efficacy. A challenging novel therapeutic concept is vaccination against nicotine. An efficient vaccine would generate antibodies that sequester nicotine in the blood and prevent its access to the brain. The vaccine would have great potential for treating nicotine addiction and for relapse prevention. We reviewed the current status of vaccines against nicotine addiction that are undergoing clinical trials or are in preclinical development. We discuss problems associated with the development of nicotine vaccines, their efficacy in addiction treatment, challenges and ethical concerns. Existing evidence indicates that nicotine vaccination is well tolerated and capable of inducing an immune response but its effectiveness in increasing smoking abstinence has not been shown so far. PMID:23108361

Nicotine place preference in the mouse: influences of prior handling, dose and strain and attenuation by nicotinic receptor antagonists.

PubMed

Grabus, Sheri D; Martin, Billy R; Brown, Sharon E; Damaj, M Imad

2006-03-01

Although conditioned place preferences (CPPs) are seen with most abused drugs, nicotine does not always produce a preference in this design. The goals of the present experiment were to (1) examine various factors that could contribute to these inconsistent results and (2) begin to evaluate the specific nicotinic receptors involved in the nicotine CPP. The influences of prior handling, environmental habituation, and injection habituation on a nicotine CPP were first evaluated in ICR mice. Subsequently, various nicotine doses were assessed for their abilities to produce a CPP, and the effectiveness of nicotinic receptor antagonists in attenuating this preference was examined. Finally, nicotine CPPs were assessed in C57BL/6J and DBA/2J mice to examine the influence of strain in this design. Nicotine CPPs were seen in handled/environmentally habituated, but not in unhandled, ICR mice. Habituation to the injection techniques failed to strengthen the preference. In ICR mice, a CPP was seen with one intermediate dose of nicotine. This CPP was attenuated by mecamylamine and dihydro-beta-erythroidine (DHbetaE). A nicotine CPP was also seen in C57BL/6J, but not in DBA/2J, mice. Earlier handling experience and strain are important factors when evaluating a nicotine CPP in the mouse. In addition, certain nicotinic receptors underlie the nicotine CPP, indicating that this model can elucidate underlying mediators of nicotine reward.

Comprehensive Chemical Characterization of Rapé Tobacco Products: Nicotine, Un-ionized Nicotine, Tobacco-specific N’-Nitrosamines, Polycyclic Aromatic Hydrocarbons, and Flavor Constituents

PubMed Central

Stanfill, Stephen B.; da Silva, André Luiz Oliveira; Lisko, Joseph G.; Lawler, Tameka S.; Kuklenyik, Peter; Tyx, Robert E.; Peuchen, Elizabeth H.; Richter, Patricia; Watson, Clifford H.

2017-01-01

Rapé, a diverse group of smokeless tobacco products indigenous to South America, is generally used as a nasal snuff and contains substantial amount of plant material with or without tobacco. Previously uncharacterized, rapé contains addictive and harmful chemicals that may have public health implications for users. Here we report % moisture, pH and the levels of total nicotine, un-ionized nicotine, flavor-related compounds, tobacco-specific N-nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) for manufactured and hand-made rapé. Most rapé products were mildly acidic (pH 5.17 – 6.23) with total nicotine ranging from 6.32 to 47.6 milligram per gram of sample (mg/g). Calculated un-ionized nicotine ranged from 0.03 to 18.5 mg/g with the highest values associated with hand-made rapés (pH 9.75 – 10.2), which contain alkaline ashes. In tobacco-containing rapés, minor alkaloid levels and Fourier transform infrared spectra were used to confirm the presence of Nicotiana rustica, a high nicotine tobacco species. There was a wide concentration range of TSNAs and PAHs among the rapés analyzed. Several TSNAs and PAHs identified in the products are known or probable carcinogens according to the International Agency for Research in Cancer. Milligram quantities of some non-tobacco constituents, such as camphor, coumarin, and eugenol, warrant additional evaluation. PMID:25934468

Comprehensive chemical characterization of Rapé tobacco products: Nicotine, un-ionized nicotine, tobacco-specific N'-nitrosamines, polycyclic aromatic hydrocarbons, and flavor constituents.

PubMed

Stanfill, Stephen B; Oliveira da Silva, André Luiz; Lisko, Joseph G; Lawler, Tameka S; Kuklenyik, Peter; Tyx, Robert E; Peuchen, Elizabeth H; Richter, Patricia; Watson, Clifford H

2015-08-01

Rapé, a diverse group of smokeless tobacco products indigenous to South America, is generally used as a nasal snuff and contains substantial amount of plant material with or without tobacco. Previously uncharacterized, rapé contains addictive and harmful chemicals that may have public health implications for users. Here we report % moisture, pH, and the levels of total nicotine, un-ionized nicotine, flavor-related compounds, tobacco-specific N-nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) for manufactured and hand-made rapé. Most rapé products were mildly acidic (pH 5.17-6.23) with total nicotine ranging from 6.32 to 47.6 milligram per gram of sample (mg/g). Calculated un-ionized nicotine ranged from 0.03 to 18.5 mg/g with the highest values associated with hand-made rapés (pH 9.75-10.2), which contain alkaline ashes. In tobacco-containing rapés, minor alkaloid levels and Fourier transform infrared spectra were used to confirm the presence of Nicotiana rustica, a high nicotine tobacco species. There was a wide concentration range of TSNAs and PAHs among the rapés analyzed. Several TSNAs and PAHs identified in the products are known or probable carcinogens according to the International Agency for Research on Cancer. Milligram quantities of some non-tobacco constituents, such as camphor, coumarin, and eugenol, warrant additional evaluation. Published by Elsevier Ltd.

Discriminative-stimulus effects of NS9283, a nicotinic α4β2* positive allosteric modulator, in nicotine-discriminating rats.

PubMed

Mohler, Eric G; Franklin, Stanley R; Rueter, Lynne E

2014-01-01

Neuronal α4β2* nicotinic acetylcholine receptors mediate cognition, pain, and the discriminative and reinforcing effects of nicotine. In addition to traditional orthosteric agonists, α4β2* positive allosteric modulators (PAMs) have recently been identified. With increased subtype selectivity relative to agonists, PAMs administered alone or in combination with low-dose α4β2* agonists may be used as powerful tools for increasing our understanding of α4β2* pharmacology. The present experiments tested the nicotine discriminative-stimulus effects of the α4β2* PAM NS9283 (A-969933) in the presence and absence of low-dose nicotine or nicotinic subtype-selective agonist. Rats were trained to discriminate 0.4 mg/kg nicotine from saline in a two-lever drug discrimination paradigm. In subsequent generalization tests, rats were administered nicotine, the α4β2*-preferring agonist ABT-594, and NS9283, alone or in two-drug combinations. Nicotine and ABT-594 showed dose-dependent nicotine generalization. NS9283 alone resulted in a non-significant increase in nicotine-appropriate lever selection. Combination of non-effective doses of nicotine or ABT-594 with escalating doses of NS9283 resulted in a complete conversion to 100 % nicotine-appropriate choice in the case of nicotine combination and incomplete, though significant, generalization for ABT-594. The α4β2* PAM NS9283 alone did not produce nicotine-like discriminative effects, but did demonstrate dose-related increases in nicotine lever choice when combined with a non-effective dose of nicotine or the α4β2* agonist ABT-594. This finding provides confirmation of the positive allosteric modulating effect of NS9283 in a functional in vivo paradigm. NS9283 is a potentially valuable tool for studying the role of α4β2* receptors in various nicotinic acetylcholine receptor-related functions.

E-cigarette nicotine content and labelling practices in a restricted market: Findings from Ontario, Canada.

PubMed

Czoli, Christine D; Goniewicz, Maciej L; Palumbo, Mary; White, Christine M; Hammond, David

2018-05-04

Although several countries, including Canada, have prohibited the sale of nicotine-containing e-cigarettes, there is little evidence examining the impact of such regulatory measures on nicotine content and labelling. E-cigarettes were systematically purchased at 80 retail outlets across 4 cities in Ontario, Canada in January-February 2015. Products' nicotine content and labelling accuracy were assessed using gas chromatography. A total of 166 e-cigarette products were purchased, including disposable products (33%), refillable products (14%), and e-liquids (53%). Similar proportions of products were labelled as 'without nicotine' (41%), and 'with nicotine' (44%), while 15% of products were unlabelled. Analyses revealed that almost half the products (48%) contained nicotine. With respect to the presence of nicotine, 10 products (6%) were mislabelled. Just over one-quarter (27%) of products labelled as 'with nicotine' (n = 73) fell outside their labelled concentration. All of the mislabelled products were e-liquids (100%) and the vast majority were sold in vape shops (90%). Despite a prohibition, nicotine-containing e-cigarettes are commonly sold in Canada. While many e-cigarettes were correctly labelled, inaccuracies were common, particularly among nicotine-containing products sold in vape shops. The findings reflect limitations regarding the design and enforcement of the current e-cigarette regulatory framework. Copyright © 2018 Elsevier B.V. All rights reserved.

Low Nicotine Content Descriptors Reduce Perceived Health Risks and Positive Cigarette Ratings in Participants Using Very Low Nicotine Content Cigarettes.

PubMed

Denlinger-Apte, Rachel L; Joel, Danielle L; Strasser, Andrew A; Donny, Eric C

2017-10-01

Understanding how smokers perceive reduced nicotine content cigarettes will be important if the FDA and global regulatory agencies implement reduced nicotine product standards for cigarettes. Prior research has shown that some smokers incorrectly believe "light" cigarettes are less harmful than regular cigarettes. Similar misunderstandings of health risk could also apply to reduced nicotine cigarettes. To date, most studies of reduced nicotine cigarettes have blinded subjects to the nicotine content. Therefore, little is known about how smokers experience reduced nicotine content cigarettes when they are aware of the reduced content, and how use may be impacted. The present study was a within-subjects experiment with 68 adult daily smokers who smoked two identical very low nicotine content Quest 3 (0.05 mg nicotine yield) cigarettes. Subjects were told that one cigarette contained "average" nicotine content, and the other contained "very low" nicotine content. After smoking each cigarette, subjects completed subjective measures about their smoking experience. Subjects rated the "very low" nicotine cigarette as less harmful to their health overall compared to the "average" nicotine cigarette; this effect held true for specific smoking-related diseases. Additionally, they rated the "very low" nicotine cigarette as having less desirable subjective effects than the "average" nicotine cigarette and predicted having greater interest in quitting smoking in the future if only the "very low" nicotine cigarette was available. Explicit knowledge of very low nicotine content changes smokers' perceptions of very low nicotine content cigarettes, resulting in reduced predicted harm, subjective ratings and predicted future use. Before a reduced nicotine product standard for cigarettes can be implemented, it is important to understand how product information impacts how smokers think about and experience very low nicotine content cigarettes. Prior research has shown that smokers

Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

PubMed Central

Garcia, Kristine L P; Coen, Kathy; Miksys, Sharon; Lê, Anh Dzung; Tyndale, Rachel F

2015-01-01

The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The gene that encodes human CYP2B6 is highly polymorphic, where the variation in brain enzyme levels could result in altered brain drug levels. CYP2B can metabolize nicotine, the main psychoactive ingredient in cigarettes; if altered brain CYP2B activity can influence nicotine brain levels, it could influence nicotine-mediated behaviors. To investigate this, a mechanism-based inhibitor selective for CYP2B, C8-xanthate (20 μg), was administered intracerebroventricularly (ICV) into the brain of rats, and 22 h later, nicotine levels were measured by in vivo microdialysis following nicotine (150 μg/kg intravenous). Brain nicotine levels from 15 to 30 min and the AUC0–45min were both twofold higher (p<0.05) with C8-xanthate vs vehicle pretreatment; there was no difference in peripheral nicotine levels. Rats were then given ICV pretreatment with C8-xanthate/ASCF and underwent intravenous nicotine self-administration with 3.75–30 μg/kg per infusion dose. C8-xanthate pretreatment increased responding in progressive ratio (15 μg/kg per infusion dose, p<0.05). In a separate cohort, C8-xanthate increased the percentage of rats that acquired self-administration (7.5 μg/kg per infusion dose, p<0.05) from 40% after vehicle pretreatment to 100%, with no difference in peripheral nicotine levels measured at the end of behavior. In a third cohort, C8-xanthate increased the number of sessions required to meet extinction criteria (p<0.05). Together these data demonstrate that the brain CYP2B activity can influence nicotine brain levels and subsequent behaviors independent of hepatic metabolism. This suggests that human smokers with variable CYP2B brain levels could have different nicotine levels and reinforcement, which might have a role in smoking behaviors and dependence. PMID:25652250

Developing a model of limited-access nicotine consumption in C57Bl/6J mice.

PubMed

Kasten, C R; Frazee, A M; Boehm, S L

2016-09-01

Although United States smoking rates have been on the decline over the past few decades, cigarette smoking still poses a critical health and economic threat. Very few treatment options for smoking exist, and many of them do not lead to long-term abstinence. Preclinical models are necessary for understanding the effects of nicotine and developing treatments. Current self-administration models of nicotine intake may require surgical procedures and often result in low levels of intake. Further, they do not lend themselves to investigating treatments. The current study sought to develop a limited-access model of nicotine intake using the Drinking-in-the-Dark paradigm, which results in high levels of binge-like ethanol consumption that can be pharmacologically manipulated. The present study found that mice will consume nicotine under a range of parameters. Intakes under the preferred condition of 0.14mg/ml nicotine in 0.2% saccharin reached over 6mg/kg in two hours and were reduced by an injection of R(+)-baclofen. Mecamylamine did not significantly affect nicotine consumption. As nicotine and ethanol are often co-abused, nicotine intake was also tested in the presence of ethanol. When presented in the same bottle, mice altered nicotine intake under various concentrations to maintain consistent levels of ethanol intake. When nicotine and ethanol were presented in separate bottles, mice greatly reduced their nicotine intake while maintaining ethanol intake. In conclusion, these studies characterize a novel model of limited-access nicotine intake that can be pharmacologically manipulated. Copyright © 2016 Elsevier Inc. All rights reserved.

Origin of polycyclic aromatic hydrocarbons and other organic pollutants in the air particles of subway stations in Barcelona.

PubMed

van Drooge, Barend L; Prats, Raimon M; Reche, Cristina; Minguillón, MariCruz; Querol, Xavier; Grimalt, Joan O; Moreno, Teresa

2018-06-09

Underground subways transport large numbers of citizens in big cities, which must breathe air with limited ventilation. These atmospheric conditions may enhance the concentration of air pollutants from both outdoor and indoor air. The influence of ventilation conditions and maintenance activities on the concentrations of air pollutants have been studied. Particulate matter with aerodynamic diameter smaller than 2.5 μm (PM 2.5 ) in indoor air was sampled in ten platforms of nine subway stations of the metropolitan area of Barcelona in 2015 and 2016. These particles were analyzed for polycyclic aromatic hydrocarbons (PAH) and organic tracer compounds. The concentrations of PAH were in the range of the street air levels with higher PAH values in the colder period. No influence of nighttime maintenance activities was observed on the platform air quality during daytime. Source apportionment analysis using the concentrations of hopanes, nicotine and levoglucosan as molecular tracer compounds showed that 75% of the detected PAH at the platforms have an outdoor PM origin. The modern subway stations, with advanced ventilation and platform screen doors that separate the subway system from the platform, showed lowest PAH and PM concentrations. Copyright © 2018. Published by Elsevier B.V.

Smoking cessation during alcohol treatment: a randomized trial of combination nicotine patch plus nicotine gum.

PubMed

Cooney, Ned L; Cooney, Judith L; Perry, Bridget L; Carbone, Michael; Cohen, Emily H; Steinberg, Howard R; Pilkey, David T; Sevarino, Kevin; Oncken, Cheryl A; Litt, Mark D

2009-09-01

The primary aim was to compare the efficacy of smoking cessation treatment using a combination of active nicotine patch plus active nicotine gum versus therapy consisting of active nicotine patch plus placebo gum in a sample of alcohol-dependent tobacco smokers in an early phase of out-patient alcohol treatment. A secondary aim was to determine whether or not there were any carry-over effects of combination nicotine replacement on drinking outcomes. Small-scale randomized double-blind placebo-controlled clinical trial with 1-year smoking and drinking outcome assessment. Two out-patient substance abuse clinics provided a treatment platform of behavioral alcohol and smoking treatment delivered in 3 months of weekly sessions followed by three monthly booster sessions. Participants were 96 men and women with a diagnosis of alcohol abuse or dependence and smoking 15 or more cigarettes per day. All participants received open-label transdermal nicotine patches and were randomized to receive either 2 mg nicotine gum or placebo gum under double-blind conditions. Analysis of 1-year follow-up data revealed that patients receiving nicotine patch plus active gum had better smoking outcomes than those receiving patch plus placebo gum on measures of time to smoking relapse and prolonged abstinence at 12 months. Alcohol outcomes were not significantly different across medication conditions. Results of this study were consistent with results of larger trials of smokers without alcohol problems, showing that combination therapy (nicotine patch plus gum) is more effective than monotherapy (nicotine patch) for smoking cessation.

Neuronal nicotinic acetylcholine receptors: neuroplastic changes underlying alcohol and nicotine addictions

PubMed Central

Feduccia, Allison A.; Chatterjee, Susmita; Bartlett, Selena E.

2012-01-01

Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug's reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine's effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies. PMID:22876217

Nicotine evokes kinetic tremor by activating the inferior olive via α7 nicotinic acetylcholine receptors.

PubMed

Kunisawa, Naofumi; Iha, Higor A; Shimizu, Saki; Tokudome, Kentaro; Mukai, Takahiro; Kinboshi, Masato; Serikawa, Tadao; Ohno, Yukihiro

2016-11-01

Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of movement disorders (e.g., tremor) and epilepsy. Here, we performed behavioral and immunohistochemical studies using mice and rats to elucidate the mechanisms underlying nicotine-induced tremor. Treatments of animals with nicotine (0.5-2mg/kg, i.p.) elicited kinetic tremor, which was completely suppressed by the nACh receptor antagonist mecamylamine (MEC). The specific α7 nACh receptor antagonist methyllycaconitine (MLA) also inhibited nicotine-induced tremor, whereas the α4β2 nACh antagonist dihydro-β-erythroidine (DHβE) or the peripheral α3β4 nACh antagonist hexamethonium showed no effects. Mapping analysis of Fos protein expression, a biological marker of neural excitation, revealed that a tremorgenic dose (1mg/kg) of nicotine region-specifically elevated Fos expression in the piriform cortex (PirC), medial habenula, solitary nucleus and inferior olive (IO) among 44 brain regions examined. In addition, similarly to the tremor responses, nicotine-induced Fos expression in the PirC and IO was selectively antagonized by MLA, but not by DHβE. Furthermore, an electrical lesioning of the IO, but not the PirC, significantly suppressed the induction of nicotine tremor. The present results suggest that nicotine elicits kinetic tremor in rodents by activating the IO neurons via α7 nACh receptors. Copyright © 2016 Elsevier B.V. All rights reserved.

A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.

The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the developmentmore » and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.« less

Oxidative stress induced by Porphyromonas gingivalis lysate and nicotine in human periodontal ligament fibroblasts.

PubMed

Nguyen, Thuy Thu; Huynh, Nam Nhat-Cong; Seubbuk, Sujiwan; Nilmoje, Thanapoj; Wanasuntronwong, Aree; Surarit, Rudee

2018-06-29

Porphyromonas gingivalis (P. gingivalis) and nicotine have been implicated as a major pathogen in the development and progression of periodontitis. One of the possible mechanism is via the oxidative stress of human periodontal ligament fibroblasts (PDLF) which lead to the damage of cell viability and function. This study aimed to investigate oxidative stress (OS) levels in the cultured media of human PDLF under the induction of P. gingivalis lysate and nicotine. Primary PDLF was cultured in growth media under P. gingivalis or/and nicotine treatment in different concentrations for 2 and 24 h. Following incubation, oxidative stress molecules malondialdehyde (MDA) and oxidized guanine species (Ox-GS) from the cell cultured supernatant were determined by spectrophotometric assay and ELISA, respectively. DCFDA and superoxide assays were performed to verify the production of ROS and intracellular superoxide radical under various stimuli. As a result, at both 2 and 24 h, Ox-GS and MDA levels in the medium of cells treated with different concentrations of P. gingivalis lysate and nicotine, either separately or in combination, were significantly different from the negative controls in a dose- and time-dependent manner. Interestingly, except MDA levels in P. gingivalis lysate at 20 µg/ml, MDA levels in all other tested conditions were found as same as one in the positive controls after 24 h. ROS and superoxide production were enhanced under P. gingivalis and/or nicotine stimulation. Therefore, OS biomarkers were generated by PDLF upon treatment with periodontal pathogens and nicotine which could elucidate a potential local mechanism of periodontal disease etiology via superoxide mediation.

Neonatal Nicotine Exposure Increases Excitatory Synaptic Transmission and Attenuates Nicotine-stimulated GABA release in the Adult Rat Hippocampus

PubMed Central

Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

2014-01-01

Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1–7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking. PMID:24950455

Determination of nicotine by surface-enhanced Raman scattering (SERS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barber, T.E.; List, M.S.; Haas, J.W. III

1994-11-01

The analytical application of surface-enhanced Raman spectroscopy (SERS) to the determination of nicotine is demonstrated. A simple spectroelectrochemical method using a copper or silver electrode as the SERS substrate has been developed, consisting of three steps: polishing a working electrode to a mirror finish; roughening the electrode in an electrolyte solution; and, finally, depositing the nicotine analyte onto the roughened electrode after immersion in a sample solution. During the reduction cycle, a large enhancement in nicotine Raman scattering is observed at the electrode surface. The intensity of the SERS signal on a silver electrode is linear with concentration from 10more » to 900 ppb, with an estimated detection limit of 7 ppb. The total analysis time per sample is approximately five minutes. This procedure has been used to analyze the extract from a cigarette side-stream smoke sample (environmental tobacco smoke); the SERS results agree well with those of conventional gas chromatographic analysis.« less

Nicotinic alteration of decision-making.

PubMed

Naudé, Jérémie; Dongelmans, Malou; Faure, Philippe

2015-09-01

Addiction to nicotine is characterized by impulses, urges and lack of self-control towards cigarettes. A key element in the process of addiction is the development of habits oriented towards nicotine consumption that surpass flexible systems as a consequence of a gradual adaptation to chronic drug exposure. However, the long-term effects of nicotine on brain circuits also induce wide changes in decision-making processes, affecting behaviors unrelated to cigarettes. This review aims at providing an update on the implications of nicotine on general decision-making processes, with an emphasis on impulsivity and risk-taking. As impulsivity is a rather ambiguous behavioral trait, we build on economic and normative theories to better characterize these nicotine-induced alterations in decision-making. Nonetheless, experimental data are sparse and often contradictory. We will discuss how the latest findings on the neurobiological basis of choice behavior may help disentangling these issues. We focus on the role of nicotine acetylcholine receptors and their different subunits, and on the spatio-temporal dynamics (i.e. diversity of the neural circuits, short- and long-term effects) of both endogenous acetylcholine and nicotine action. Finally, we try to link these neurobiological results with neuro-computational models of attention, valuation and action, and of the role of acetylcholine in these decision processes. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exposure to ethanol and nicotine induces stress responses in human placental BeWo cells.

PubMed

Repo, Jenni K; Pesonen, Maija; Mannelli, Chiara; Vähäkangas, Kirsi; Loikkanen, Jarkko

2014-01-13

Human placental trophoblastic cancer BeWo cells can be used as a model of placental trophoblasts. We found that combined exposure to relevant exposure concentrations of ethanol (2‰) and nicotine (15 μM) induces an increase in the amount of reactive oxygen species (ROS). Neither ethanol or nicotine alone, nor their combination affected cell viability. However, nicotine decreased cell proliferation, both alone and combined with ethanol. Nicotine increased the expression of the endoplasmic reticulum (ER)-stress related protein GRP78/BiP, but not another marker of ER-stress, IRE1α. We also studied the effects of nicotine and/or ethanol on phosphorylation and expression of three mitogen-activated protein kinases (MAPKs), i.e. JNK, p38 and ERK1/2. Nicotine decreased the phosphorylation of JNK and also had similar effect on total amount of this protein. Phosphorylation and expression of p38 were increased 1.7- and 1.6-fold, respectively, by nicotine alone, and 1.9- and 2.1-fold by the combined treatment. Some increase (1.8-fold) was also seen in the phosphorylation of ERK2 at 48 h, in cells exposed to both ethanol and nicotine. This study shows that ethanol and nicotine, which harm the development of fetus may induce both oxidative and ER stress responses in human placental trophoblastic cells, implicating these mechanisms in their fetotoxic effects. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

PACAP Protects Against Ethanol and Nicotine Toxicity in SH-SY5Y Cells: Implications for Drinking-Smoking Co-morbidity.

PubMed

Manavalan, Sridharan; Getachew, Bruk; Manaye, Kebreten F; Khundmiri, Syed J; Csoka, Antonei B; McKinley, Raechel; Tamas, Andrea; Reglodi, Dora; Tizabi, Yousef

2017-07-01

The detrimental effects of heavy drinking and smoking are multiplied when the two are combined. Treatment modalities for each and especially for the combination are very limited. Although in low concentration, alcohol and nicotine, each may have beneficial effects including neuroprotection, their combination, instead of providing additive protection, may actually lead to toxicity in cell cultures. Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous 38 amino-acid peptide with demonstrated protection against neuronal injury, trauma as well as various endogenous and exogenous toxic agents. The aim of this study was to investigate whether PACAP may also protect against toxicity induced by high alcohol, high nicotine, or the combination of low alcohol and nicotine concentrations, and if so, whether this effect was mediated via PAC1 receptor. We used the neuroblastoma-derived SH-SY5Y cells and applied various colorimetric assays for determination of cell viability or toxicity. Results indicate that PACAP blocks toxicity induced by high alcohol and high nicotine as well as their combination at low concentrations. The effects of PACAP in turn were blocked by the PACAP antagonist (PACAP 6-38), indicating involvement of the PACAP receptor PAC1 and possibly vasoactive intestinal peptide (VIP) receptors in PACAP's protection. Moreover, no combined toxicity of low alcohol and low nicotine could be detected in calcium-free medium. These findings suggest possible beneficial effects of PACAP in preventing alcohol and nicotine toxicity and that calcium contributes to the damage induced by combination of low alcohol and nicotine in SH-SY5Y cells.

Thujone inhibits the function of α7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm.

PubMed

Sultan, Ahmed; Yang, Keun-Hang Susan; Isaev, Dmitro; Nebrisi, Eslam El; Syed, Nurulain; Khan, Nadia; Howarth, Christopher F; Sadek, Bassem; Oz, Murat

2017-06-01

Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α 7 subunit of the human nicotinic acetylcholine (α 7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100μM)-induced currents with an IC 50 value of 24.7μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca 2+ -dependent Cl - channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [ 125 I] α-bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human α 7 nACh receptor indicated that thujone suppressed choline induced Ca 2+ transients in a concentration-dependent manner. In rat hippocampal CA3-dentate gyrus synapses, nicotine-induced enhancement of long-term potentiation was also inhibited by thujone. Furthermore, the results observed in in-vivo one-trial passive avoidance paradigm show that thujone (1.25mg/kg, i.p.) significantly impaired nicotine-induced enhancement of learning and memory in Wistar rats. Collectively, our results indicate that thujone inhibits the function of the α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

IMPACT OF AN OZONE GENERATOR AIR CLEANER ON STYRENE CONCENTRATIONS IN AN INDOOR AIR QUALITY RESEARCH CHAMBER

EPA Science Inventory

The paper gives results of an investigation of the impact of an ozone generator air cleaner on vapor-phase styrene concentrations in a full-scale indoor air quality test chamber. The time history of the concentrations of styrene and ozone is well predicted by a simulation model u...

Forensic implication of muscle level of nicotine in an adipocere body found in the sea.

PubMed

Nishimura, Hiroyuki; Furumiya, Junichi; Nakanishi, Akinori; Hashimoto, Yoshiaki

2009-04-01

We reported previously that blood levels of nicotine in suicidal smokers tend to be significantly higher than those in non-suicidal smokers, and blood level of nicotine seems to be a useful criterion for discriminating suicide from other types of death. In this paper, we report nicotine and cotinine levels in various tissues of an adipocere body found in the sea. The cause of death was drowning, and the postmortem time interval was approximately 5 months at autopsy. His driver's license was concealed in his sock, which seemed to suggest that he committed to suicide. In toxicological analysis by gas chromatography, nicotine and cotinine in the femoral muscle were detected at concentrations of 213 and 488 ng/g, respectively, and these substances were also detected in the brain, liver and kidney. For evaluating the tissue levels of nicotine and cotinine in the adipocere body, we analyzed these levels in blood and various tissues of 13 autopsy cases of smokers. Nicotine and cotinine levels in blood were the most similar to those in skeletal muscle. Although the postmortem time interval, the formation process of adipocere and the environmental condition in water may affect nicotine and cotinine levels in the femoral muscle, the high muscle level of nicotine in the present case seem to implicate suicidal death.

Comparison of environmental tobacco smoke (ETS) concentrations generated by an electrically heated cigarette smoking system and a conventional cigarette.

PubMed

Tricker, Anthony R; Schorp, Matthias K; Urban, Hans-Jörg; Leyden, Donald; Hagedorn, Heinz-Werner; Engl, Johannes; Urban, Michael; Riedel, Kirsten; Gilch, Gerhard; Janket, Dinamis; Scherer, Gerhard

2009-01-01

Smoking conventional lit-end cigarettes results in exposure of nonsmokers to potentially harmful cigarette smoke constituents present in environmental tobacco smoke (ETS) generated by sidestream smoke emissions and exhaled mainstream smoke. ETS constituent concentrations generated by a conventional lit-end cigarette and a newly developed electrically heated cigarette smoking system (EHCSS) that produces only mainstream smoke and no sidestream smoke emissions were investigated in simulated "office" and "hospitality" environments with different levels of baseline indoor air quality. Smoking the EHCSS (International Organisation for Standardization yields: 5 mg tar, 0.3 mg nicotine, and 0.6 mg carbon monoxide) in simulated indoor environments resulted in significant reductions in ETS constituent concentrations compared to when smoking a representative lit-end cigarette (Marlboro: 6 mg tar, 0.5 mg nicotine, and 7 mg carbon monoxide). In direct comparisons, 24 of 29 measured smoke constituents (83%) showed mean reductions of greater than 90%, and 5 smoke constituents (17%) showed mean reductions between 80% and 90%. Gas-vapor phase ETS markers (nicotine and 3-ethenylpyridine) were reduced by an average of 97% (range 94-99%). Total respirable suspended particles, determined by online particle measurements and as gravimetric respirable suspended particles, were reduced by 90% (range 82-100%). The mean and standard deviation of the reduction of all constituents was 94 +/- 4%, indicating that smoking the new EHCSS in simulated "office" and "hospitality" indoor environments resulted in substantial reductions of ETS constituents in indoor air.

E-cigarette puffing patterns associated with high and low nicotine e-liquid strength: effects on toxicant and carcinogen exposure.

PubMed

Cox, Sharon; Kośmider, Leon; McRobbie, Hayden; Goniewicz, Maciej; Kimber, Catherine; Doig, Mira; Dawkins, Lynne

2016-09-20

Contrary to intuition, use of lower strength nicotine e-liquids might not offer reduced health risk if compensatory puffing behaviour occurs. Compensatory puffing (e.g. more frequent, longer puffs) or user behaviour (increasing the wattage) can lead to higher temperatures at which glycerine and propylene glycol (solvents used in e-liquids) undergo decomposition to carbonyl compounds, including the carcinogens formaldehyde and acetaldehyde. This study aims to document puffing patterns and user behaviour associated with using high and low strength nicotine e-liquid and associated toxicant/carcinogen exposure in experienced e-cigarette users (known as vapers herein). A counterbalanced repeated measures design. Non-tobacco smoking vapers; have used an e-cigarette for ≥3 months; currently using nicotine strength e-liquid ≥12mg/mL and a second or third generation device. This study will measure puffing patterns in vapers whilst they use high and low strength nicotine e-liquid under fixed and user-defined settings, each for a week. The 4 counterbalanced conditions are: i) low strength (6mg/mL), fixed settings; ii) low strength user-defined settings; iii) high strength (18mg/mL) fixed settings; iv) high strength user-defined settings. Biomarkers of exposure to toxicants and carcinogens will be measured in urine. In the second phase of this study, toxicant yields will be measured in aerosol generated using a smoking machine operated to replicate the puffing behaviours of each participant. i) Puffing patterns (mean puff number, puff duration, inter-puff interval and mL of liquid consumed) and user behaviour (changes to device settings: voltage and air-flow) associated with using high and low strength nicotine e-liquid. ii) Toxicant/carcinogen exposure associated with the puffing patterns/device settings used by our participants. i) Subjective effects. ii) comparisons with toxicant exposure from tobacco smoke (using documented evidence) and with recommended safety limits

Platelet activation, adhesion, inflammation, and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine concentrations.

PubMed

Hom, Sarah; Chen, Li; Wang, Tony; Ghebrehiwet, Berhane; Yin, Wei; Rubenstein, David A

2016-11-01

Tobacco smoke extracts prepared from both mainstream and sidestream smoking have been associated with heightened platelet activation, aggregation, adhesion, and inflammation. Conversely, it has been shown that pure nicotine inhibits similar platelet functions. In this work, we 1) evaluated the effects of e-cigarette extracts on platelet activities and 2) elucidated the differences between the nicotine-dependent and non-nicotine dependent (e.g. fine particulate matter or toxic compounds) effects of tobacco and e-cigarette products on platelet activities. To accomplish these goals, platelets from healthy volunteers (n = 50) were exposed to tobacco smoke extracts, e-cigarette vapor extracts, and pure nicotine and changes in platelet activation, adhesion, aggregation, and inflammation were evaluated, using optical aggregation, flow cytometry, and ELISA methods. Interestingly, the exposure of platelets to e-vapor extracts induced a significant up-regulation in the expression of the pro-inflammatory gC1qR and cC1qR and induced a marked increase in the deposition of C3b as compared with traditional tobacco smoke extracts. Similarly, platelet activation, as measured by a prothrombinase based assay, and platelet aggregation were also significantly enhanced after exposure to e-vapor extracts. Finally, platelet adhesion potential toward fibrinogen, von Willebrand factor, and other platelets was also enhanced after exposure to e-cigarette vapor extracts. In the presence of pure nicotine, platelet functions were observed to be inhibited, which further suggests that other constituents of tobacco smoke and electronic vapor can antagonize platelet functions, however, the presence of nicotine in extracts somewhat perpetuated the platelet functional changes in a dose-dependent manner.

Variations in Label Information and Nicotine Levels in Electronic Cigarette Refill Liquids in South Korea: Regulation Challenges

PubMed Central

Kim, Sungroul; Goniewicz, Maciej L.; Yu, Sol; Kim, Bokyeong; Gupta, Ribhav

2015-01-01

Background: In South Korea, the consumption of liquid nicotine used in electronic cigarettes has dramatically increased from 4310 L in 2012 to 7220 L in 2013. This study aimed to examine the level of heterogeneity of contents of the labels and discrepancy of the nicotine content between that indicated on the label and the actual values for electronic cigarette liquid refill products in South Korea. Methods: We purchased 32 electronic cigarette liquid refill products (17 Korean domestic, 15 imported ones) and one pure nicotine product at six different electronic cigarette retail stores in Seoul between May and June 2014. The actual nicotine concentrations of each product were measured by a blinded analyst at Roswell Park Cancer Institute, Buffalo, NY, USA. Results: Three out of 15 imported liquid refill products provided manufacturing dates, while expiration dates were available on eight products. The range of nicotine concentration was from “not detected” to 17.5 mg/mL. Labeling discrepancies of the concentrations ranged from −32.2% to 3.3% among electronic cigarette liquid refill products. The highest concentration (150.3 ± 7.9 mg/mL) was found in a sample labeled as “pure nicotine”. Conclusions: There is no standardization of labelling among electronic cigarette liquids sampled from retail stores and the labels did not accurately reflect the content. One product labeled “pure nicotine” raises concerns, since it may be poisonous to consumers, especially to children. This study revealed the urgent need for the development of product regulations in South Korea. PMID:25950652

Use Behaviors, Dependence, and Nicotine Exposure Associated with Ad Libitum Cigar Smoking

PubMed Central

Claus, Eric D.; Moeller, Benjamin C.; Harbour, Darlene; Kuehl, Philip J.; McGuire, Michael; Vivar, Juan C.; Schroeder, Megan J.

2018-01-01

Objectives To examine factors important to cigar smoking and subsequent nicotine exposure, we evaluated the impact of cigar type, cigarette smoking history, and inhalation behaviors on nicotine dependence, smoking topography, and biomarkers of exposure in current exclusive cigar smokers. Methods Adult, exclusive cigar smokers (N = 77) were recruited based on cigar type, cigarette smoking history, and self-reported inhalation behaviors. Participants smoked their own brand product ad libitum for up to one hour; dependence symptoms, smoking topography, and biomarkers of exposure were assessed. Results Cigar smokers showed low levels of dependence. Cigar smoking alleviated withdrawal and craving symptoms, increased plasma nicotine concentration, and increased exhaled CO. Multiple regression analyses indicate that inhalation behaviors were associated with increased dependence and greater reductions in withdrawal symptoms upon cigar smoking. Large cigar smokers smoked longer and smoked more tobacco than small cigar and cigarillo smokers. Furthermore, large cigar smokers and self-reported inhalers were exposed to more nicotine than small cigar smokers and non-inhalers. Conclusions Our study suggests that cigar type and smoking behaviors affect dependence and nicotine exposure upon cigar smoking. These findings provide additional insight into the substantial risks associated with cigar smoking. PMID:29516029

Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability.

PubMed

Stiles, Mitchell F; Campbell, Leanne R; Graff, Donald W; Jones, Bobbette A; Fant, Reginald V; Henningfield, Jack E

2017-09-01

Electronic cigarettes (ECs) are becoming popular alternatives for smokers, but there has been limited study of their abuse liability. The objective of this study was to evaluate the abuse liability of three Vuse Solo ECs, ranging from 14 to 36 mg in nicotine content, relative to high- and low-abuse liability comparator products (usual brand combustible cigarettes and nicotine gum, respectively) in a group of 45 EC-naïve smokers. Enrolled subjects' ratings of subjective effects and nicotine uptake over 6 h were used to measure abuse liability and pharmacokinetics following in-clinic use of each EC. Use of Vuse Solo resulted in subjective measures and nicotine uptake that were between those of combustible cigarettes and nicotine gum, although generally closer to nicotine gum. Compared to combustible cigarettes, use of Vuse Solo resulted in significantly lower scores in measures of product liking, positive effects, and intent to use again. These pharmacodynamic findings were consistent with the pharmacokinetic data, showing that cigarettes produced substantially faster and higher levels of nicotine uptake as compared to Vuse Solo and nicotine gum. Vuse Solo resulted in more rapid initial uptake of nicotine compared to nicotine gum, but peak concentration and long-term extent of uptake were not different or were lower with Vuse. Collectively, these findings suggest that Vuse Solo likely has an abuse liability that is somewhat greater than nicotine gum but lower than cigarettes. ClinicalTrials.gov identifier: NCT02269514.

Low concentrations of persistent organic pollutants (POPs) in air at Cape Verde.

PubMed

Nøst, Therese Haugdahl; Halse, Anne Karine; Schlabach, Martin; Bäcklund, Are; Eckhardt, Sabine; Breivik, Knut