Tobacco-induced neuronal degeneration via cotinine in rats subjected to experimental spinal cord injury.

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Dalgic, Ali; Okay, Onder; Helvacioglu, Fatma; Daglioglu, Ergun; Akdag, Rifat; Take, Gulnur; Belen, Deniz

2013-05-01

Cigarette smoke contains over 4000 chemicals including well-characterized toxicants and carcinogens, among which is cotinine. Cotinine is the principal metabolite of nicotine that has adverse affects on the microcirculation via vasoconstriction, hypoxia and the wound-healing cascade. Its impact on spinal cord injury (SCI) has not been investigated yet. The aim of the present study is to investigate the cotinine effect on SCI. 48 male Wistar rats were divided into six groups as follows: sham-control, sham-trauma, vehicle-control, vehicle-trauma, cotinine-control, and cotinine-trauma. Initially, a defined concentration of cotinine blood level was maintained by daily intraperitoneal injection of cotinine for 14 days in the cotinine groups. The concentration was similar to the cotinine dose in the blood level of heavy smokers. Only ethyl alcohol was injected in the vehicle groups during the same period. Then, SCI was performed by a Tator clip. The cotinine groups were compared with rats subjected to vehicle and sham groups by immunohistochemical biomarkers such as glial fibrillary acidic protein (GFAP) and 2,3-cyclic nucleotide 3-phosphodiesterase (CNP) expressions. Electron microscopic examination was also performed. GFAP-positive cells were noted to be localized around degenerated astrocytes. Marked vacuolization with perivascular and perineural edema was seen in the cotinin consumption groups. These findings showed the inhibition of regeneration after SCI. Similarly, vacuolization within myelin layers was noted in the cotinine groups, which was detected through reduced CNP expression. Cotinine, a main metabolite of nicotine, has harmful effects on SCI via GFAP and CNP expression. The findings of the present study support the hypothesis that tobacco causes neuronal degeneration via cotinine. Georg Thieme Verlag KG Stuttgart · New York.

Race, gender, and nicotine metabolism in adolescent smokers.

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Rubinstein, Mark L; Shiffman, Saul; Rait, Michelle A; Benowitz, Neal L

2013-07-01

Differences in the rate of nicotine metabolism between genders and different races have been hypothesized to contribute to disparities in smoking rate, susceptibility to addiction, and ability to quit smoking. The purpose of this study was to determine the effect of race and gender on the rate of nicotine metabolism as indicated by the nicotine metabolite ratio (NMR) in adolescent smokers. One hundred and fifty-nine adolescent smokers aged 13-17 were given 2mg of deuterium-labeled cotinine (cotinine-d4). The NMR was calculated as the ratio of concentrations of deuterium-labeled 3'-hydroxycotinine (ng/ml) to cotinine-d4 (ng/ml) in saliva and is a validated biomarker of the rate of nicotine metabolism. The sample was 67.3% female and racially mixed. On average, Whites had the fastest rates of metabolism compared with both Blacks/African Americans (p smokers, racial variations in rates of nicotine metabolism were similar to those that have been reported in adult smokers. In contrast to findings in adult smokers, the NMR did not vary significantly by gender or self-reported hormone use.

Nicotine demethylation in Nicotiana cell suspension cultures: N'-formylnornicotine is not involved.

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Bartholomeusz, Trixie Ann; Bhogal, Ramneek K; Molinié, Roland; Felpin, François-Xavier; Mathé-Allainmat, Monique; Meier, Anna-Carolin; Dräger, Birgit; Lebreton, Jacques; Roscher, Albrecht; Robins, Richard J; Mesnard, François

2005-10-01

Nicotine or nornicotine enriched with stable isotopes in either the N'-methyl group or the pyrrolidine-N were fed to Nicotiana plumbaginifolia suspension cell cultures that do not form endogenous nicotine. The metabolism of these compounds was investigated by analysing the incorporation of isotope into other alkaloids using gas chromatography-mass spectroscopy (GC-MS). Nicotine metabolism primarily resulted in the accumulation of nornicotine, the N'-demethylation product. In addition, six minor metabolites appeared during the course of nicotine metabolism, four of which were identified as cotinine, myosmine, N'-formylnornicotine and N'-carboethoxynornicotine. While cotinine was formed from [(13)C,(2)H(3)-methyl]nicotine without dilution of label, N'-formylnornicotine was labelled at only about 6% of the level of nicotine and N'-carboethoxynornicotine was unlabelled. Feeding with [1'-(15)N]nornicotine resulted in incorporation without dilution of label into both N'-formylnornicotine and N'-carboethoxynornicotine. This pattern strongly indicates that, while nornicotine and cotinine are derived directly from nicotine, N'-formylnornicotine and N'-carboethoxynornicotine are metabolites of nornicotine. Thus, it is directly demonstrated that N'-formylnornicotine is not an intermediate in nicotine demethylation.

Assessment of urinary cotinine as a marker of nicotine absorption from tobacco leaves: a study on tobacco farmers in Malaysia.

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Onuki, Mayumi; Yokoyama, Kazuhito; Kimura, Kaoru; Sato, Hajime; Nordin, Rusli Bin; Naing, Lin; Morita, Yoko; Sakai, Tadashi; Kobayashi, Yasuki; Araki, Shunichi

2003-05-01

To assess dermal absorption of nicotine from tobacco leaves in relation to Green Tobacco Sickness (GTS), urinary cotinine concentrations were measured in 80 male tobacco-growing farmers and in 40 healthy males (controls) who did not handle wet tobacco leaves in Kelantan, Malaysia. Among non-smokers, urinary cotinine levels in farmers were significantly higher than those of controls; farmers with urinary cotinine of 50 ng/ml/m2 or above showed eye symptoms more frequently than those below this level (ptobacco farmers evidence a risk of nicotine poisoning from tobacco leaves, assessment including GTS together with effects of pesticides will be necessary.

The metabolic fate of nectar nicotine in worker honey bees.

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du Rand, Esther E; Pirk, Christian W W; Nicolson, Susan W; Apostolides, Zeno

2017-04-01

Honey bees (Apis mellifera) are generalist pollinators that forage for nectar and pollen of a very large variety of plant species, exposing them to a diverse range of secondary metabolites produced as chemical defences against herbivory. Honey bees can tolerate high levels of many of these toxic compounds, including the alkaloid nicotine, in their diet without incurring apparent fitness costs. Very little is known about the underlying detoxification processes mediating this tolerance. We examined the metabolic fate of nicotine in newly emerged worker bees using radiolabeled nicotine and LC-MS/MS analysis to determine the kinetic distribution profile of nicotine as well as the absence or presence and identity of any nicotine-derived metabolites. Nicotine metabolism was extensive; virtually no unmetabolised nicotine were recovered from the rectum. The major metabolite found was 4-hydroxy-4-(3-pyridyl) butanoic acid, the end product of 2'C-oxidation of nicotine. It is the first time that 4-hydroxy-4-(3-pyridyl) butanoic acid has been identified in an insect as a catabolite of nicotine. Lower levels of cotinine, cotinine N-oxide, 3'hydroxy-cotinine, nicotine N-oxide and norcotinine were also detected. Our results demonstrated that formation of 4-hydroxy-4-(3-pyridyl) butanoic acid is quantitatively the most significant pathway of nicotine metabolism in honey bees and that the rapid excretion of unmetabolised nicotine does not contribute significantly to nicotine tolerance in honey bees. In nicotine-tolerant insects that do not rely on the rapid excretion of nicotine like the Lepidoptera, it is possible that the 2'C-oxidation of nicotine is the conserved metabolic pathway instead of the generally assumed 5'C-oxidation pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Utility and Cutoff Value of Hair Nicotine as a Biomarker of Long-Term Tobacco Smoke Exposure, Compared to Salivary Cotinine

Directory of Open Access Journals (Sweden)

Sungroul Kim

2014-08-01

Full Text Available While hair samples are easier to collect and less expensive to store and transport than biological fluids, and hair nicotine characterizes tobacco exposure over a longer time period than blood or urine cotinine, information on its utility, compared with salivary cotinine, is still limited. We conducted a cross-sectional study with 289 participants (107 active smokers, 105 passive smokers with self-reported secondhand smoke (SHS exposure, and 77 non-smokers with no SHS exposure in Baltimore (Maryland, USA. A subset of the study participants (n = 52 were followed longitudinally over a two-month interval.  Median baseline hair nicotine concentrations for active, passive and non-smokers were 16.2, 0.36, and 0.23 ng/mg, respectively, while those for salivary cotinine were 181.0, 0.27, and 0.27 ng/mL, respectively. Hair nicotine concentrations for 10% of passive or non-smokers were higher than the 25th percentile value for active smokers while all corresponding salivary cotinine concentrations for them were lower than the value for active smokers. This study showed that hair nicotine concentration values could be used to distinguish active or heavy passive adult smokers from non-SHS exposed non-smokers. Our results indicate that hair nicotine is a useful biomarker for the assessment of long-term exposure to tobacco smoke.

A high-throughput robotic sample preparation system and HPLC-MS/MS for measuring urinary anatabine, anabasine, nicotine and major nicotine metabolites.

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Wei, Binnian; Feng, June; Rehmani, Imran J; Miller, Sharyn; McGuffey, James E; Blount, Benjamin C; Wang, Lanqing

2014-09-25

Most sample preparation methods characteristically involve intensive and repetitive labor, which is inefficient when preparing large numbers of samples from population-scale studies. This study presents a robotic system designed to meet the sampling requirements for large population-scale studies. Using this robotic system, we developed and validated a method to simultaneously measure urinary anatabine, anabasine, nicotine and seven major nicotine metabolites: 4-Hydroxy-4-(3-pyridyl)butanoic acid, cotinine-N-oxide, nicotine-N-oxide, trans-3'-hydroxycotinine, norcotinine, cotinine and nornicotine. We analyzed robotically prepared samples using high-performance liquid chromatography (HPLC) coupled with triple quadrupole mass spectrometry in positive electrospray ionization mode using scheduled multiple reaction monitoring (sMRM) with a total runtime of 8.5 min. The optimized procedure was able to deliver linear analyte responses over a broad range of concentrations. Responses of urine-based calibrators delivered coefficients of determination (R(2)) of >0.995. Sample preparation recovery was generally higher than 80%. The robotic system was able to prepare four 96-well plate (384 urine samples) per day, and the overall method afforded an accuracy range of 92-115%, and an imprecision of labor-saving for sample preparation, making it efficient and practical for routine measurements in large population-scale studies such as the National Health and Nutrition Examination Survey (NHANES) and the Population Assessment of Tobacco and Health (PATH) study. Published by Elsevier B.V.

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

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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

2016-09-01

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 was 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. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of nicotine and cotinine in hair by on-line in-tube solid-phase microextraction coupled with liquid chromatography-tandem mass spectrometry as biomarkers of exposure to tobacco smoke.

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Inukai, Takehito; Kaji, Sanae; Kataoka, Hiroyuki

2018-07-15

Smoking not only increases the risk of lung cancer but is strongly related to the onset of cardiovascular disease. Particularly, passive smoking due to sidestream smoke is a critical public health problem. To assess active and passive exposure to tobacco smoke, we developed a simple and sensitive method, consisting of on-line in-tube solid phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS), to determine nicotine and its metabolite cotinine in hair samples. These compounds were separated within 5 min using a Polar-RP80A column and detected in the positive ion mode by multiple reaction monitoring. The optimum in-tube SPME conditions were 25 draw/eject cycles of 40 μL of sample at a flow rate of 200 μL/min using a Carboxen 1006 capillary column as an extraction device. The extracted compounds in the stationary phase on the inner wall of the capillary could be dissolved easily into the mobile phase and transferred to an LC column. Using the in-tube SPME LC-MS/MS method, the calibration curves were linear in the 5-1000 pg/mL ranges for nicotine and cotinine, and the detection limits (signal to noise ratio of 3) were 0.45 and 0.13 pg/mL, respectively. The intra-day and inter-day precisions were below 3.4% and 6.0% (n = 5), respectively. This method was utilized successfully to analyze pg/mg levels of nicotine and cotinine in 1 mg of hairs without interference peaks, and good recoveries were obtained. The concentration of cotinine in hair was two orders of magnitude lower than that of nicotine, but a good positive correlation was found between the concentrations of these compounds. This method can automate the extraction, concentration and analysis of samples, and is useful for the assessment of long-term exposure to tobacco smoke. Copyright © 2018 Elsevier B.V. All rights reserved.

Concentration of perfluorinated compounds and cotinine in human foetal organs, placenta, and maternal plasma

DEFF Research Database (Denmark)

Mamsen, Linn Salto; Jönsson, Bo A.G.; Lindh, Christian H.

2017-01-01

levels. Foetal exposure has previously been estimated from umbilical cord plasma, but the actual concentration in foetal organs has never been measured. Objectives The concentrations of 5 PFASs and cotinine – the primary metabolite of nicotine – were measured in human foetuses, placentas, and maternal...... plasma to evaluate to what extent these compounds were transferred from mother to foetus and to determine if the PFAS concentrations were associated with maternal cigarette smoking. Methods Thirty-nine Danish women who underwent legal termination of pregnancy before gestational week 12 were included; 24...... ratio for all five PFASs and cotinine. Smokers presented 99 ng/g cotinine in plasma, 108 ng/g in placenta, and 61 ng/g in foetal organs. No correlation between the maternal cotinine concentrations and PFAS concentrations was found. Conclusions PFASs were transferred from mother to foetus, however...

Levels of saliva cotinine in electronic cigarette users.

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Etter, Jean-François

2014-05-01

To assess saliva cotinine levels in experienced users of e-cigarettes ('vapers'). An internet survey in 2011 and 2012, with collection of saliva vials by mail. Participants were 71 users of e-cigarettes enrolled mainly on websites and online forums dedicated to e-cigarettes. Use of e-cigarettes, tobacco and nicotine medications. Collection of saliva by mail and analysis of cotinine by liquid chromatography-mass spectrometry. Most participants (89%) were former smokers, most (92%) were using e-cigarettes daily, had been using e-cigarettes for 12 months on average and puffed a median of 150 times per day on their e-cigarettes [mean = 220 puffs/day, 95% confidence interval (CI) = 169-271]. The median concentration of nicotine in refill liquids was 16 mg/ml (mean = 16.4, 95% CI = 14.5-18.3). In the 62 e-cigarette users who, in the past 5 days, had not used any tobacco or nicotine medications, the median cotinine level was 353 ng/ml (mean = 374, 95% CI = 318-429), the correlation between cotinine and nicotine concentration in e-liquids was r = 0.33 (P = 0.013), and the correlation between cotinine and the number of cigarettes smoked per day before quitting smoking was r = 0.48 (P Addiction.

Slower nicotine metabolism among postmenopausal Polish smokers.

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Kosmider, Leon; Delijewski, Marcin; Koszowski, Bartosz; Sobczak, Andrzej; Benowitz, Neal L; Goniewicz, Maciej L

2018-06-01

A non-invasive phenotypic indicator of the rate of nicotine metabolism is nicotine metabolite ratio (NMR) defined as a ratio of two major metabolites of nicotine - trans-3'-hydroxycotinine/cotinine. The rate of nicotine metabolism has important clinical implications for the likelihood of successful quitting with nicotine replacement therapy (NRT). We conducted a study to measure NMR among Polish smokers. In a cross-sectional study of 180 daily cigarette smokers (42% men; average age 34.6±13.0), we collected spot urine samples and measured trans-3'-hydroxycotinine (3-HC) and cotinine levels with LC-MS/MS method. We calculated NMR (molar ratio) and analyzed variations in NMR among groups of smokers. In the whole study group, an average NMR was 4.8 (IQR 3.4-7.3). The group of women below 51 years had significantly greater NMR compared to the rest of the population (6.4; IQR 4.1-8.8 vs. 4.3; IQR 2.8-6.4). No differences were found among group ages of male smokers. This is a first study to describe variations in nicotine metabolism among Polish smokers. Our findings indicate that young women metabolize nicotine faster than the rest of population. This finding is consistent with the known effects of estrogen to induce CYP2A6 activity. Young women may require higher doses of NRT or non-nicotine medications for most effective smoking cessation treatment. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

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

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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.

Increased hepatic nicotine elimination after phenobarbital induction in the conscious rat

International Nuclear Information System (INIS)

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

1990-01-01

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 the 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

Monitoring nicotine intake from e-cigarettes: measurement of parent drug and metabolites in oral fluid and plasma.

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Papaseit, Esther; Farré, Magí; Graziano, Silvia; Pacifici, Roberta; Pérez-Mañá, Clara; García-Algar, Oscar; Pichini, Simona

2017-03-01

Electronic cigarettes (e-cig) known as electronic nicotine devices recently gained popularity among smokers. Despite many studies investigating their safety and toxicity, few examined the delivery of e-cig-derived nicotine and its metabolites in alternative biological fluids. We performed a randomized, crossover, and controlled clinical trial in nine healthy smokers. Nicotine (NIC), cotinine (COT), and trans-3'-hydroxycotinine (3-HCOT) were measured in plasma and oral fluid by liquid chromatography-tandem mass spectrometry after consumption of two consecutive e-cig administrations or two consecutive tobacco cigarettes. NIC and its metabolites were detected both in oral fluid and plasma following both administration conditions. Concentrations in oral fluid resulted various orders of magnitude higher than those observed in plasma. Oral fluid concentration of tobacco cigarette and e-cig-derived NIC peaked at 15 min after each administration and ranged between 1.0 and 1396 μg/L and from 0.3 to 860 μg/L; those of COT between 52.8 and 110 μg/L and from 33.8 to 94.7 μg/L; and those of 3-HCOT between 12.4 and 23.5 μg/L and from 8.5 to 24.4 μg/L. The oral fluid to plasma concentration ratio of both e-cig- and tobacco cigarette-derived NIC peaked at 15 min after both administrations and correlated with oral fluid NIC concentration. The obtained results support the measurement of NIC and metabolites in oral fluid in the assessment of intake after e-cig use and appear to be a suitable alternative to plasma when monitoring nicotine delivery from e-cig for clinical and toxicological studies.

Solid-phase extraction and HPLC assay of nicotine and cotinine in plasma and brain.

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Dawson, Ralph; Messina, S M; Stokes, C; Salyani, S; Alcalay, N; De Fiebre, N C; De Fiebre, C M

2002-01-01

The aim of this study was to develop a simple and reliable assay for nicotine (NIC) and its major metabolite, cotinine (COT), in plasma and brain. A method was developed that uses an extraction method compatible with reverse-phase high-performance liquid chromatography (HPLC) separation and ultraviolet (UV) detection. Sequential solid-phase extraction on silica columns followed by extraction using octadecyl (C18) columns resulted in mean percent recovery (n = 5) of 51 +/- 5, 64 +/- 10, and 52 +/- 10% for NIC, COT, and phenylimidazole (PI), respectively, in spiked 1-mL serum samples. Recovery (mean +/- SEM) of the internal standard (PI) from spiked samples of nicotine-injected rats averaged 64.1 +/- 1.5% (n = 138) from plasma, and 20.7+/-0.8% (n = 128) from brain. The limits of detection of NIC in plasma samples were approximately 8 ng per mL, and of COT, 13.6 ng per mL. Further optimization of our extraction method, using slower flow rates and solid-phase extraction on silica columns, followed by C18 column extraction, yielded somewhat better recoveries (38 +/-3%) for 1-mL brain homogenates. Interassay precision (coefficient of variation) was determined on the basis of daily calibrations for 2 months and was found to be 7%, 9%, and 9% for NIC, COT, and PI, respectively, whereas intra-assay variability was 3.9% for both NIC and COT. Limited studies were performed on analytical columns for comparison of retention, resolution, asymmetry, and column capacity. We concluded that a simple two-step solid-phase extraction method, coupled with HPLC separation and UV detection, can be used routinely to measure NIC and COT in biological fluids and tissues.

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

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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; pnicotine, cotinine and nicotine/cotinine ratios may be useful for determining smoking recency in “spot samples” collected during nicotine cessation treatment. PMID:21860341

The selectively bred high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats differ in sensitivity to nicotine.

Science.gov (United States)

de Fiebre, NancyEllen C; Dawson, Ralph; de Fiebre, Christopher M

2002-06-01

Studies in rodents selectively bred to differ in alcohol sensitivity have suggested that nicotine and ethanol sensitivities may cosegregate during selective breeding. This suggests that ethanol and nicotine sensitivities may in part be genetically correlated. Male and female high alcohol sensitivity (HAS), control alcohol sensitivity, and low alcohol sensitivity (LAS) rats were tested for nicotine-induced alterations in locomotor activity, body temperature, and seizure activity. Plasma and brain levels of nicotine and its primary metabolite, cotinine, were measured in these animals, as was the binding of [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin in eight brain regions. Both replicate HAS lines were more sensitive to nicotine-induced locomotor activity depression than the replicate LAS lines. No consistent HAS/LAS differences were seen on other measures of nicotine sensitivity; however, females were more susceptible to nicotine-induced seizures than males. No HAS/LAS differences in nicotine or cotinine levels were seen, nor were differences seen in the binding of nicotinic ligands. Females had higher levels of plasma cotinine and brain nicotine than males but had lower brain cotinine levels than males. Sensitivity to a specific action of nicotine cosegregates during selective breeding for differential sensitivity to a specific action of ethanol. The differential sensitivity of the HAS/LAS rats is due to differences in central nervous system sensitivity and not to pharmacokinetic differences. The differential central nervous system sensitivity cannot be explained by differences in the numbers of nicotinic receptors labeled in ligand-binding experiments. The apparent genetic correlation between ethanol and nicotine sensitivities suggests that common genes modulate, in part, the actions of both ethanol and nicotine and may explain the frequent coabuse of these agents.

A one-year monitoring of nicotine use in sport: frontier between potential performance enhancement and addiction issues.

Science.gov (United States)

Marclay, François; Grata, Elia; Perrenoud, Laurent; Saugy, Martial

2011-12-10

Tobacco consumption is a global epidemic responsible for a vast burden of disease. With pharmacological properties sought-after by consumers and responsible for addiction issues, nicotine is the main reason of this phenomenon. Accordingly, smokeless tobacco products are of growing popularity in sport owing to potential performance enhancing properties and absence of adverse effects on the respiratory system. Nevertheless, nicotine does not appear on the 2011 World Anti-Doping Agency (WADA) Prohibited List or Monitoring Program by lack of a comprehensive large-scale prevalence survey. Thus, this work describes a one-year monitoring study on urine specimens from professional athletes of different disciplines covering 2010 and 2011. A method for the detection and quantification of nicotine, its major metabolites (cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide) and minor tobacco alkaloids (anabasine, anatabine and nornicotine) was developed, relying on ultra-high pressure liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-TQ-MS/MS). A simple and fast dilute-and-shoot sample treatment was performed, followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) data acquisition. After method validation, assessing the prevalence of nicotine consumption in sport involved analysis of 2185 urine samples, accounting for 43 different sports. Concentrations distribution of major nicotine metabolites, minor nicotine metabolites and tobacco alkaloids ranged from 10 (LLOQ) to 32,223, 6670 and 538 ng/mL, respectively. Compounds of interest were detected in trace levels in 23.0% of urine specimens, with concentration levels corresponding to an exposure within the last three days for 18.3% of samples. Likewise, hypothesizing conservative concentration limits for active nicotine consumption prior and/or during

Known and Novel Sources of Variability in the Nicotine Metabolite Ratio in a Large Sample of Treatment-Seeking Smokers

Science.gov (United States)

Chenoweth, Meghan J.; Novalen, Maria; Hawk, Larry W.; Schnoll, Robert A.; George, Tony P.; Cinciripini, Paul M.; Lerman, Caryn; Tyndale, Rachel F.

2014-01-01

Background The ratio of 3′hydroxycotinine to cotinine, or nicotine metabolite ratio (NMR), is strongly associated with CYP2A6 genotype, CYP2A6-mediated nicotine and cotinine metabolism, and nicotine clearance. Higher NMR (faster nicotine clearance) is associated retrospectively with heavier smoking and lower cessation rates. Methods NMR as a predictive biomarker of cessation outcomes is being investigated (NCT01314001). In addition to strong CYP2A6-genetic influences on NMR, demographic and hormonal factors alter NMR. Here we analyzed, for the first time together, these sources of variation on NMR in smokers screened for this clinical trial (N=1672). Results Participants (mean age=45.9) were 65.1% Caucasian, 34.9% African American, and 54.8% male. Mean NMR (SD) was higher in Caucasians vs. African Americans (0.41(0.20) vs. 0.33(0.21); P<0.001), and in females vs. males (0.41(0.22) vs. 0.37(0.20); P<0.001). Among females, birth control pill use (N=17) and hormone replacement therapy (N=14) were associated with 19.5% (P=0.09) and 29.3% (P=0.06) higher mean NMR, respectively, albeit non-significantly. BMI was negatively associated with NMR (Rho=−0.14; P<0.001), while alcohol use (Rho=0.11; P<0.001) and cigarette consumption (Rho=0.12; P<0.001) were positively associated with NMR. NMR was 16% percent lower in mentholated cigarette users (P<0.001). When analyzed together in a linear regression model, these predictors (each ≤2%) accounted for <8% of total NMR variation. Conclusions While these factors significantly affected NMR, they contributed little (together <8%; each ≤2%) to total NMR variation. Impact Thus when using NMR, for example to prospectively guide smoking cessation therapy, these sources of variation are unlikely to cause NMR misclassification. PMID:25012994

Detoxification and elimination of nicotine by nectar-feeding birds.

Science.gov (United States)

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.

Cotinine improves visual recognition memory and decreases cortical Tau phosphorylation in the Tg6799 mice.

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Grizzell, J Alex; Patel, Sagar; Barreto, George E; Echeverria, Valentina

2017-08-01

Alzheimer's disease (AD) is associated with the progressive aggregation of hyperphosphorylated forms of the microtubule associated protein Tau in the central nervous system. Cotinine, the main metabolite of nicotine, reduced working memory deficits, synaptic loss, and amyloid β peptide aggregation into oligomers and plaques as well as inhibited the cerebral Tau kinase, glycogen synthase 3β (GSK3β) in the transgenic (Tg)6799 (5XFAD) mice. In this study, the effect of cotinine on visual recognition memory and cortical Tau phosphorylation at the GSK3β sites Serine (Ser)-396/Ser-404 and phospho-CREB were investigated in the Tg6799 and non-transgenic (NT) littermate mice. Tg mice showed short-term visual recognition memory impairment in the novel object recognition test, and higher levels of Tau phosphorylation when compared to NT mice. Cotinine significantly improved visual recognition memory performance increased CREB phosphorylation and reduced cortical Tau phosphorylation. Potential mechanisms underlying theses beneficial effects are discussed. Copyright © 2017. Published by Elsevier Inc.

Cigarette nicotine yields and nicotine intake among Japanese male workers

OpenAIRE

Ueda, K; Kawachi, I; Nakamura, M; Nogami, H; Shirokawa, N; Masui, S; Okayama, A; Oshima, A

2002-01-01

Objectives: To analyse brand nicotine yield including "ultra low" brands (that is, cigarettes yielding ≤ 0.1 mg of nicotine by Federal Trade Commission (FTC) methods) in relation to nicotine intake (urinary nicotine, cotinine and trans-3'-hydroxycotinine) among 246 Japanese male smokers.

Urinary cotinine levels of electronic cigarette (e-cigarette) users.

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Göney, Gülşen; Çok, İsmet; Tamer, Uğur; Burgaz, Sema; Şengezer, Tijen

2016-07-01

The popularity of electronic cigarettes (e-cigarettes) is rapidly increasing in many countries. These devices are designed to imitate regular cigarettes, delivering nicotine via inhalation without combusting tobacco but currently, there is a lack of scientific evidence on the presence or absence of nicotine exposure. Such research relies on evidence from e-cigarette users urine samples. In this study, we aimed to determine the levels and compare the amount of nicotine to which e-cigarette users, cigarette smokers and passive smokers are exposed. Therefore, urine samples were collected from e-cigarette users, cigarette smokers, passive smokers, and healthy nonsmokers. The urinary cotinine levels of the subjects were determined using gas chromatography-mass spectrometry. The mean (±SD) urinary cotinine levels were determined as 1755 ± 1848 ng/g creatinine for 32 e-cigarette users, 1720 ± 1335 ng/g creatinine for 33 cigarette smokers and 81.42 ± 97.90 ng/g creatinine for 33 passive smokers. A significant difference has been found between cotinine levels of e-cigarette users and passive smokers (p e-cigarette users and cigarette smokers (p > 0.05). This is a seminal study to demonstrate the e-cigarette users are exposed to nicotine as much as cigarette smokers.

Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.

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Michael A Ha

Full Text Available Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8, the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may

Interlaboratory comparability of serum cotinine measurements at smoker and nonsmoker concentration levels: A round-robin study

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Jacob, Peyton; Holiday, David B.; Benowitz, Neal L.; Sosnoff, Connie S.; Doig, Mira V.; Feyerabend, Colin; Aldous, Kenneth M.; Sharifi, Mehran; Kellogg, Mark D.; Langman, Loralie J.

2009-01-01

Introduction: Cotinine, the primary proximate metabolite of nicotine, is commonly measured as an index of exposure to tobacco in both active users of tobacco and nonsmokers with possible exposure to secondhand smoke (SHS). A number of laboratories have implemented analyses for measuring serum cotinine in recent years, but there have been few interlaboratory comparisons of the results. Among nonsmokers exposed to SHS, the concentration of cotinine in blood can be quite low, and extensive variability in these measurements has been reported in the past. Methods: In this study, a group of seven laboratories, all experienced in serum cotinine analysis, measured eight coded serum pools with concentrations ranging from background levels of about 0.05 ng/ml to relatively high concentrations in the active smokers range. All laboratories used either gas–liquid chromatography with nitrogen–phosphorus detection or liquid chromatography with mass spectrometric detection. Results: All seven laboratories reliably measured the cotinine concentrations in samples that were within the range of their methods. In each case, the results for the pools were correctly ranked in order, and no significant interlaboratory bias was observed at the 5% level of significance for results from any of the pools. Discussion: We conclude that present methods of chromatographic analysis of serum cotinine, as used by these experienced laboratories, are capable of providing accurate and precise results in both the smoker and the nonsmoker concentration range. PMID:19933777

Evaluation of Dried Urine Spot Method to Screen Cotinine among Tobacco Dependents: An Exploratory Study.

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Jain, Raka; Quraishi, Rizwana; Verma, Arpita

2017-01-01

Assessment of cotinine, a metabolite of nicotine in body fluids, is an important approach for validating the self-report among tobacco users. Adaptation of assays on dried urine spots (DUSs) has advantages of ease of collection, transportation, minimal invasiveness, and requirement of small volume. The aim of the present study was to develop an efficient method for testing cotinine in DUSs and evaluating its clinical applicability. This involved optimization of conditions for detection, recovery, and stability of cotinine from dried urine, spotted on filter paper. Enzyme-linked immunosorbent assay was used for screening, whereas confirmation was done by gas chromatography. For clinical applicability, urine samples of tobacco users were tested. Water was found to be a suitable extracting solvent as compared to carbonate-bicarbonate buffer (pH 9.2) and saline. Screening was achieved by two punches taken from a 20 μl (diameter 1.3 cm) spotted urine samples, and confirmation was achieved by five complete circles each of 20 μl sample volume. The recovery was found to be 97% in water. Limit of detection for the method was found to be 100 ng/ml. No signs of significant degradation were found under all storage conditions. All the urine samples of tobacco users were found to be positive by a conventional method as well as DUSs, and the method proved to be efficient. DUS samples are a useful alternative for biological monitoring of recent nicotine use, especially in developing countries where sample logistics could be an important concern.

A longitudinal study of cotinine in long-term daily users of e-cigarettes.

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Etter, Jean-François

2016-03-01

It is not clear whether, in established vapers, cotinine levels remain stable or change over time. We enrolled 98 exclusive users of e-cigarettes on websites and forums dedicated to smoking cessation and to e-cigarettes. We collected saliva vials by mail in 2013-2014 (baseline), and collected a second saliva vial eight months later (follow-up) in the same participants. Participants had not used any tobacco or nicotine medications in the previous five days. Cotinine in saliva was analyzed with liquid chromatography-mass spectrometry. Use of e-cigarettes, tobacco and nicotine medications was self-reported. All participants were former smokers, and 99% were using e-cigarettes daily. They had already been using e-cigarettes for nine months on average at baseline. The median cotinine level was 252ng/mL at baseline (quartiles: 124-421ng/mL) and 307ng/mL at follow-up (114-466ng/mL, W=0.9, p=0.4 for change over time). The median concentration of nicotine in refill liquids was 11mg/mL at baseline (quartiles: 6-15mg/mL) and 6mg/mL at follow-up (5-12mg/mL) (Wilcoxon signed rank test: W=5.2, p<0.001 for change over time). The median volume of e-liquid used per month was 80mL at baseline (quartiles: 50-130mL) and 100mL at follow-up (60-157mL, W=3.3, p=0.001 for change over time). In experienced e-cigarette users enrolled online, cotinine levels were similar to levels usually observed in cigarette smokers. Over time, these users decreased the concentration of nicotine in their e-liquids, but increased their consumption of e-liquid in order to maintain their cotinine levels constant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

'Real-world' compensatory behaviour with low nicotine concentration e-liquid: subjective effects and nicotine, acrolein and formaldehyde exposure.

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Dawkins, Lynne; Cox, Sharon; Goniewicz, Maciej; McRobbie, Hayden; Kimber, Catherine; Doig, Mira; Kośmider, Leon

2018-06-07

To compare the effects of i) high versus low nicotine concentration e-liquid, ii) fixed versus adjustable power and iii) the interaction between the two on: a) vaping behaviour, b) subjective effects, c) nicotine intake, and d) exposure to acrolein and formaldehyde in e-cigarette users vaping in their everyday setting. Counterbalanced, repeated measures with four conditions: i) low nicotine (6 mg/mL)/fixed power; ii) low nicotine/adjustable power; iii) high nicotine (18 mg/mL)/fixed power; iv) high nicotine/adjustable power. London and the South East, England. Twenty experienced e-cigarette users (recruited between September 2016 and February 2017) vaped ad libitum using an eVic Supreme™ with a 'Nautilus Aspire' tank over four weeks (one week per condition). Puffing patterns (daily puff number [PN], puff duration [PD], inter-puff interval [IPI]), mL of e-liquid consumed, changes to power (where permitted), and subjective effects (urge to vape, nicotine withdrawal symptoms) were measured in each condition. Nicotine intake was measured via salivary cotinine. 3-hydroxypropylmercapturic acid (3-HPMA), a metabolite of the toxicant acrolein, and formate, a metabolite of the carcinogen formaldehyde, were measured in urine. There was a significant nicotine concentration x power interaction for PD (p<0.01). PD was longer with low nicotine/fixed power compared with i) high nicotine/fixed power (p< 0.001 and ii) low nicotine/adjustable power (p< 0.01). PN and liquid consumed were higher in the low versus high nicotine condition (main effect of nicotine, p<0.05). Urge to vape and withdrawal symptoms were lower, and nicotine intake was higher, in the high nicotine condition (main effects of nicotine: p<0.01). Whilst acrolein levels did not differ, there was a significant nicotine x power interaction for formaldehyde (p<0.05). Use of a lower nicotine concentration e-liquid may be associated with compensatory behaviour (e.g., higher number and duration of puffs) and increases

The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice.

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McGrath-Morrow, Sharon A; Hayashi, Madoka; Aherrera, Angela; Lopez, Armando; Malinina, Alla; Collaco, Joseph M; Neptune, Enid; Klein, Jonathan D; Winickoff, Jonathan P; Breysse, Patrick; Lazarus, Philip; Chen, Gang

2015-01-01

Electronic cigarette (E-cigarettes) emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth. Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG) or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI) method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml). After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (pE-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

International Nuclear Information System (INIS)

Biegon, A.; Kim, S.-W.; Logan, J.; Hooker, J.M.; Muench, L.; Fowler, J.S.

2010-01-01

Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor ( 11 C)vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Nicotine administration produced significant, dose-dependent reductions in ( 11 C)vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.

Effect of nicotine and tobacco administration method on the mechanical properties of healing bone following closed fracture.

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Hastrup, Sidsel Gaarn; Chen, Xinqian; Bechtold, Joan E; Kyle, Richard F; Rahbek, Ole; Keyler, Daniel E; Skoett, Martin; Soeballe, Kjeld

2010-09-01

We previously showed different effects of tobacco and nicotine on fracture healing, but due to pump reservoir limits, maximum exposure period was 4 weeks. To allow flexibility in pre- and post-fracture exposure periods, the objective of this study was to compare a new oral administration route for nicotine to the established pump method. Four groups were studied: (1) pump saline, (2) pump saline + oral tobacco, (3) pump saline/nicotine + oral tobacco, and (4) pump saline + oral nicotine/tobacco. Sprague-Dawley rats (n = 84) received a transverse femoral fracture stabilized with an intramedullary pin 1 week after initiating dosing. After 3 weeks, no difference was found in torsional strength or stiffness between oral nicotine/tobacco or pump nicotine + tobacco, while energy absorption with oral nicotine/tobacco was greater than pump nicotine + tobacco (p < 0.05). Compared to saline control, strength for oral nicotine/tobacco was higher than control (p < 0.05), and stiffnesses for pump nicotine + tobacco and oral nicotine/tobacco were higher than control (p < 0.05). No differences in energy were found for either nicotine-tobacco group compared to saline control. Mean serum cotinine (stable nicotine metabolite) was different between pump and oral nicotine at 1 and 4 weeks, but all groups were in the range of 1-2 pack/day smokers. In summary, relevant serum cotinine levels can be reached in rats with oral nicotine, and, in the presence of tobacco, nicotine can influence mechanical aspects of fracture healing, dependent on administration method. Caution should be exercised when comparing results of fracture healing studies using different methods of nicotine administration. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice.

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Sharon A McGrath-Morrow

Full Text Available Electronic cigarette (E-cigarettes emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth.Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml. After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (p<.054 trial 1; p<.006 trial 2. These studies indicate that exposure to E-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

Levels of Urine Cotinine from Hookah Smoking and Exposure to Hookah Tobacco Secondhand Smoke in Hookah Lounges and Homes.

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Kassem, Nada O F; Kassem, Noura O; Liles, Sandy; Jackson, Sheila R; Posis, Alexander Ivan B; Chatfield, Dale A; Hovell, Melbourne F

2018-03-01

Nicotine, an addictive drug, is present in all forms of tobacco products, including hookah tobacco, which is not yet regulated in the United States. This study aimed to investigate the uptake of nicotine in hookah smokers and non-smokers exposed to secondhand smoke (SHS) at indoor hookah social events in natural settings where hookah tobacco was smoked exclusively. We quantified cotinine, a metabolite of nicotine, in the urine of 105 hookah smokers and 103 non-smokers. Participants provided spot urine samples the morning of and the morning after attending an indoor hookah-only smoking social event at a hookah lounge or in a private home. Following a social event where exclusively hookah tobacco was smoked, urinary cotinine levels increased significantly 8.5 times (geometric mean (GM): 16.0 ng/mg to 136.1 ng/mg) among hookah smokers, and 2.5 times (GM: 0.4 ng/mg to 1.0 ng/mg) among non-smokers exposed exclusively to hookah tobacco SHS. Among hookah smokers, the highest increase in urinary cotinine levels post a hookah event was found in occasional hookah smokers in which GM levels increased significantly 31.2 times post smoking (from 2.0 ng/mg to 62.3 ng/mg). Reported reasons for preference to smoke hookah at home by hookah smokers who attended a hookah social event in a private home included recreational purposes, socializing with friends and family, 'Me' time and relaxing at home, more comfortable to smoke hookah at home, owning a hookah and hookah tobacco, eating and drinking while smoking hookah, and saving money by smoking at home and not going to hookah lounges. Hookah tobacco smoke is a source of substantial nicotine exposure. Our results call for protecting hookah smokers' and non-smokers' health by requiring accurate hookah tobacco labels, raising taxes on hookah tobacco, reducing the spread of hookah lounges, and encouraging voluntary bans on smoking hookah tobacco in private homes.

Association of nicotine metabolism and sex with relapse following varenicline and nicotine replacement therapy.

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Glatard, Anaïs; Dobrinas, Maria; Gholamrezaee, Mehdi; Lubomirov, Rubin; Cornuz, Jacques; Csajka, Chantal; Eap, Chin B

2017-10-01

Nicotine is metabolized into cotinine and then into trans-3'-hydroxycotinine, mainly by cytochrome P450 2A6. Recent studies reported better effectiveness of varenicline in women and in nicotine normal metabolizers phenotypically determined by nicotine-metabolite ratio. Our objective was to study the influence of nicotine-metabolite ratio, CYP2A6 genotype and sex on the response to nicotine replacement therapy and varenicline. Data were extracted from a longitudinal study which included smokers participating in a smoking cessation program. Response to treatment was defined by the absence of relapse when a set threshold of reduction in cigarettes per day relative to the week before the study was no more reached. The analysis considered total and partial reduction defined by a diminution of 100% and of 90% in cigarettes per day, respectively. The hazard ratio of relapsing was estimated in multivariate Cox regression models including the sex and the nicotine metabolism determined by the phenotype or by CYP2A6 genotyping (rs1801272 and rs28399433). In the normal metabolizers determined by phenotyping and in women, the hazard ratio for relapsing was significantly lower with varenicline for a partial decrease (HR = 0.33, 95% CI [0.12, 0.89] and HR = 0.20, 95% CI [0.04, 0.91], respectively) and nonsignificantly lower for a total cessation (HR = 0.45, 95% CI [0.20, 1.0] and HR = 0.38, 95% CI [0.14, 1.0]). When compared with the normal metabolizers determined by phenotyping, the hazard ratio for a partial decrease was similar in the normal metabolizers determined by genotyping (HR = 0.42, 95% CI [0.18, 0.94]) while it was significantly lower with varenicline for a total cessation (HR = 0.50, 95% CI [0.26, 0.98]). Women and normal nicotine metabolizers may benefit more from varenicline over nicotine replacement therapy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

[Cotinine concentration in the saliva in relation to oral hygiene procedures].

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Bachanek, Teresa; Nakonieczna-Rudnicka, Marta; Piekarczyk, Wanda

2014-01-01

Cotinine is a biomarker of the exposure to the tobacco smoke, nicotine metabolite with half-life in the saliva which is 17 hours. Assessment of cotinine concentration enables among others verification of the questionnaire data as well as evaluation of both smokers and non-smokers exposure to the tobacco smoke. Practicing proper oral hygiene procedures is an essential factor of the prophylaxis of dental caries and periodontal diseases which influence general health state. The removal of dental calculus is achieved by proper teeth brushing and the use of additional oral aids. The aim of the study was evaluation of cotinine concentration in non-stimulated saliva in order to verify questionnaire data (smoker/non-smoker) and analysis of practicing oral hygiene procedures in relation to the status of cigarette smoking. Questionnaire and biochemical studies were conducted in the group of 116 people aged 20-54. In questionnaire survey 53 people (45.69%) confirmed cigarette smoking, 63 (54.31%) declared they had never smoked and never tried to smoke. Non-stimulated saliva was collected between 9(30) and 11(30), 1,5-2 hours after meal. Cotinine concentration was assayed with the use of Cotinine ELISA (Calbiotech, USA). Obtained study results were submitted to statistic analysis with the use of Chi2. Statistically essential test values were those with psmokers and 4.76% non-smokers, brushing teeth at least twice a day was reported subsequently by 73.08% and 95.24% participants. Non-smokers in comparison with smokers considerably more frequently brushed their teeth, at least twice a day (XZ=11.11, pSmokers used a toothbrush with medium hardness bristle (X2=6.05, pSmokers more fre. quently brushed their teeth improperly (X2=1 3.41, pSmokers in comparison with non-smokers did not practice proper oral hygiene which is an essential risk factor of the oral health. It is crucial for dental surgeons to conduct oral hygiene instructions in smokers as well as realization of health

Secondhand smoke exposure and serum cotinine levels among current smokers in the USA.

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Lindsay, Ryan P; Tsoh, Janice Y; Sung, Hai-Yen; Max, Wendy

2016-03-01

Secondhand smoke (SHS) likely provides additional exposure to nicotine and toxins for smokers, but has been understudied. Our objective was to determine whether SHS exposure among smokers yields detectable differences in cotinine levels compared with unexposed smokers at the population level. Using the US National Health and Nutrition Examination Survey (NHANES) for the years 1999-2012, we compared serum cotinine levels of 4547 current adult cigarette smokers stratified by self-reported SHS exposure sources (home and/or work) and smoking intensity. A weighted multivariable linear regression model determined the association between SHS exposure and cotinine levels among smokers. Smokers with SHS exposure at home (43.8%) had higher cotinine levels (β=0.483, p≤0.001) compared with those with no SHS exposure at home after controlling for the number of cigarettes smoked per day and number of days smoked in the previous 5 days, survey year, age, gender and education. Smokers with SHS exposure at work (20.0%) did not have significantly higher cotinine levels after adjustment. The adjusted geometric mean cotinine levels of light smokers (1-9 cigarettes per day) with no SHS exposure, exposure at work only, home only, and both home and work were 52.0, 62.7, 67.2, 74.4 ng/mL, respectively, compared with 219.4, 220.9, 255.2, 250.5 ng/mL among moderate/heavy smokers (≥10 cigarettes per day). Smokers living in residences where others smoke inside the home had significantly higher cotinine levels than smokers reporting no SHS exposure, regardless of individual smoking intensity. Future research should target the role that SHS exposure may have in nicotine dependence, cessation outcomes and other health impacts among smokers. 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/

Physiological and biochemical characterization of a novel nicotine-degrading bacterium Pseudomonas geniculata N1.

Directory of Open Access Journals (Sweden)

Yanghui Liu

Full Text Available Management of solid wastes with high nicotine content, such as those accumulated during tobacco manufacturing, poses a major challenge, which can be addressed by using bacteria such as Pseudomonas and Arthrobacter. In this study, a new species of Pseudomonas geniculata, namely strain N1, which is capable of efficiently degrading nicotine, was isolated and identified. The optimal growth conditions for strain N1 are a temperature of 30°C, and a pH 6.5, at a rotation rate of 120 rpm min(-1 with 1 g l(-1 nicotine as the sole source of carbon and nitrogen. Myosmine, cotinine, 6-hydroxynicotine, 6-hydroxy-N-methylmyosmine, and 6-hydroxy-pseudooxynicotine were detected as the five intermediates through gas chromatography-mass and liquid chromatography-mass analyses. The identified metabolites were different from those generated by Pseudomonas putida strains. The analysis also highlighted the bacterial metabolic diversity in relation to nicotine degradation by different Pseudomonas strains.

Nicotine Intake in Pregnant Smokers and a General Population of Smokers.

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Berlin, Ivan; Jacob, Nelly; Heishman, Stephen J

2018-01-01

The purpose of this study was to assess whether pregnant smokers have the same nicotine intake from cigarettes as a general population of smokers and whether the known lower daily cigarette consumption among pregnant smokers is associated with higher nicotine intake among pregnant smokers. The study was a cross-sectional comparison of pregnant smokers and a general population of smokers in smoking cessation clinics. Participants were treatment-seeking pregnant (n = 476), nonpregnant female (n = 116), and male (n = 195) smokers who participated in two independent smoking cessation trials. Nicotine intake was measured as saliva cotinine/ cigarette/kg body weight ratio. The mean saliva cotinine (μg/L)/ cigarette/kg body weight (0.21, SD = 0.15) of pregnant smokers was similar to that of nonpregnant female smokers (0.24, SD = 0.14) and higher than that of male smokers (0.18, SD = 0.12, p = .002) despite a substantially lower number of cigarettes per day (pregnant smokers: 12, SD = 6; nonpregnant female smokers: 26.6, SD = 11.7; male smokers: 23.5, SD = 9.5, p smokers, saliva cotinine, as expected, increased in parallel with the number of cigarettes per day, but nicotine intake (cotinine/cigarette/kg body weight) was inversely associated with daily cigarette consumption (p smokers (p = .43). This secondary analysis showed that pregnant smokers' nicotine intake was similar to that of a general population of smokers despite a lower cigarette consumption rate. Among pregnant smokers, lower daily cigarette consumption was associated with higher nicotine intake from cigarettes, suggesting compensatory smoking.

Cotinine and tobacco-specific carcinogen exposure among nondaily smokers in a multiethnic sample.

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Khariwala, Samir S; Scheuermann, Taneisha S; Berg, Carla J; Hayes, Rashelle B; Nollen, Nicole L; Thomas, Janet L; Guo, Hongfei; Ahluwalia, Jasjit S; Benowitz, Neal L

2014-05-01

Nondaily smoking has increased among current U.S. smokers during the past decade and is practiced by a significant percentage of smokers. Although research in nondaily smoking has grown, little is known about levels of exposure to tobacco toxicants among nondaily smokers and their variation across ethnic groups. We examined urinary levels of cotinine and a tobacco-specific nitrosamine (NNAL) in community participants. Associations between the biomarker data and smoking characteristics were evaluated with Spearman's correlation analysis. Participants included 28 Blacks, 4 Latinos, and 25 Whites who smoked at least 1 cigarette on 4-24 days in the past 30 days. Participants averaged 3.3 (SD = 2.1) cigarettes per day (cpd) on days smoked, they smoked an average of 13.0 (SD = 5.4) days in the past month, and they smoked nondaily for 10.5 (SD = 10.5) years. Median levels of creatinine-normalized cotinine and NNAL were 490.9 ng/mg and 140.7 pg/mg, respectively. NNAL and cotinine were highly correlated (r = .84); NNAL and cotinine were modestly correlated with cpd (r = .39 and r = .34; all p values smokers are, on average, exposed to significant levels of nicotine and carcinogenic nitrosamines, with exposures of 40%-50% of those seen in daily smokers. This level of exposure suggests a significant health risk. Nicotine and carcinogen exposure is most closely related to number of cigarettes smoked per day but not to number of days per month of smoking.

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

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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.

Racial differences in hair nicotine concentrations among smokers.

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Apelberg, Benjamin J; Hepp, Lisa M; Avila-Tang, Erika; Kim, Sungroul; Madsen, Camille; Ma, Jiemin; Samet, Jonathan M; Breysse, Patrick N

2012-08-01

In the United States, race/ethnicity is a strong determinant of tobacco use patterns, biomarkers of tobacco smoke components and metabolites, and likelihood of successful cessation. Although Black smokers tend to smoke fewer cigarettes than White smokers, they have higher cotinine levels and disease risk and lower cessation success. We examined racial differences in hair nicotine concentrations among daily tobacco smokers (n = 103) in Baltimore, Maryland. Participants completed a survey, and hair samples were collected and analyzed for nicotine concentration using gas chromatography coupled with mass spectrometry. After adjustment, hair nicotine concentrations among Black smokers were more than 5 times higher than among White smokers (95% CI 3.0, 10.5). Smokers reporting hair treatments other than coloring (bleaching, permanent, or straightening) in the past 12 months had 66% lower (95% CI 32%, 83%) hair nicotine concentrations. Smokers reporting smoking their first cigarette within 30 min of waking had twice the hair nicotine concentrations of those whose time to first cigarette was greater than 30 min after waking (95% CI 1.1, 4.2). For every additional cigarette smoked per day up to 20, mean hair nicotine concentration among all smokers increased by 4% (95% CI -1%, 9%). This study demonstrates that Black smokers have substantially higher hair nicotine levels than White smokers, after controlling for cigarettes smoked per day and other exposure sources. Time to first cigarette, cigarettes smoked per day, and use of hair treatments other than coloring were also associated with hair nicotine concentrations among smokers.

Unravelling the Conformational Landscape of Nicotinoids: the Structure of Cotinine by Broadband Rotational Spectroscopy

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Uriarte, Iciar; Ecija, Patricia; Cocinero, Emilio J.; Perez, Cristobal; Caballero-Mancebo, Elena; Lesarri, Alberto

2015-06-01

Alkaloids such as nicotine, cotinine or anabasine share a common floppy structural motif consisting of a two-ring assembly with a 3-pyridil methylamine skeleton. In order to investigate the structure-activity relationship of these biomolecules, structural studies with rotational resolution have been carried out for nicotine and anabasine in the gas phase, where these molecules can be probed in an "interaction-free" environment (no solvent or crystal-packing interactions). We hereby present a structural investigation of cotinine in a jet expansion using the chirped-pulse Fourier-transform microwave (CP-FTMW) spectrometer recently built at the University of the Basque Country (UPV-EHU). The rotational spectrum (6-18 GHz) reveals the presence of two different conformations. The conformational preferences of cotinine originate from the internal rotation of the two ring moieties, the detected species differing in a near 180° rotation of pyridine. The final structure is modulated by steric effects. J.-U. Grabow, S. Mata, J. L. Alonso, I. Peña, S. Blanco, J. C. López, C. Cabezas, Phys. Chem. Chem. Phys. 2011, 13, 21063. A. Lesarri, E. J. Cocinero, L. Evangelisti, R. D. Suenram, W. Caminati, J.-U. Grabow, Chem. Eur. J. 2010, 16, 10214.

Sex-related differences in serum cotinine concentrations in daily cigarette smokers.

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Gan, Wen Qi; Cohen, Sigal Ben-Zaken; Man, S F Paul; Sin, Don D

2008-08-01

Self-reported use of cigarettes generally underestimates the true cigarette exposure of smokers. Serum cotinine is considered the best biomarker to evaluate tobacco exposure. This study determined whether or not there were any significant differences in serum cotinine concentrations between men and women when they reported smoking the same number of cigarettes per day. We analyzed cotinine and tobacco consumption data on 680 women and 840 men, aged 20 years or older, who smoked at least 100 cigarettes during their lifetime and were still actively smoking at the time of the National Health and Nutrition Examination Surveys (1999-2002). Overall, compared with men, women reported smoking fewer cigarettes per day (16.1 vs. 18.7, ppoverty status, the use of either menthol or regular cigarettes, and the nicotine content in cigarettes, female compared with male smokers had lower serum cotinine concentrations (difference of 117.6 nmol/L; 95% CI = 42.6-192.6, p = .003). The difference was particularly notable in moderate to heavy smokers (i.e., those who smoked more than 15 cigarettes/day). These findings indicate that significant sex-related differences exist in serum cotinine levels among smokers, which suggests that self-reports may overestimate cigarette exposure in women compared with men.

Tobacco Metabolites and Caffeine in Human Milk Purchased via the Internet.

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Geraghty, Sheela R; McNamara, Kelly; Kwiek, Jesse J; Rogers, Lynette; Klebanoff, Mark A; Augustine, Molly; Keim, Sarah A

2015-11-01

Chemicals inhaled or ingested by mothers can be present in their milk. Our objective was to determine levels of nicotine, cotinine, and caffeine in human milk purchased via the Internet. We purchased human milk (n=102) via the Internet and abstracted seller advertisements for information volunteered about tobacco and caffeine use. Nicotine, cotinine, and caffeine levels in the milk were quantified by mass spectrometry according to published protocols. No sellers indicated smoking in their advertisement. Many of the milk samples (58%) had detectable nicotine or cotinine; four (4%) of the samples had nicotine or cotinine levels high enough to indicate active smoking. Twelve (12%) sellers said in their advertisements that they specifically limit (4%) or avoid (8%) caffeine entirely. Five (5%) of the samples had caffeine levels consistent with consuming at least 1 cup of coffee 2 hours prior to milk expression. Detectable amounts of caffeine were found in almost all of the samples (97%). In 102 milk samples, we detected evidence of active smoking, secondhand smoke exposure, and almost ubiquitous caffeine consumption. Buyers of human milk on the Internet should be aware that advertisements do not always include accurate information as to what substances may be present. Sellers may misrepresent their health behaviors or be unaware of lifestyle factors that can lead to exposure to nicotine and caffeine.

A prospective cohort study of biomarkers of prenatal tobacco smoke exposure: the correlation between serum and meconium and their association with infant birth weight

Directory of Open Access Journals (Sweden)

Braun Joe M

2010-08-01

Full Text Available Abstract Background The evaluation of infant meconium as a cumulative matrix of prenatal toxicant exposure requires comparison to established biomarkers of prenatal exposure. Methods We calculated the frequency of detection and concentration of tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3'-hydroxycotinine concentrations and three serial serum cotinine concentrations taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We estimated the duration and intensity of prenatal tobacco smoke exposure using serial serum cotinine concentrations and calculated geometric mean meconium tobacco smoke metabolite concentrations according to prenatal exposure. We also compared the estimated associations between these prenatal biomarkers and infant birth weight using linear regression. Results We detected nicotine (80%, cotinine (69%, and trans-3'-hydroxycotinine (57% in most meconium samples. Meconium tobacco smoke metabolite concentrations were positively associated with serum cotinine concentrations and increased with the number of serum cotinine measurements consistent with secondhand or active tobacco smoke exposure. Like serum cotinine, meconium tobacco smoke metabolites were inversely associated with birth weight. Conclusions Meconium is a useful biological matrix for measuring prenatal tobacco smoke exposure and could be used in epidemiological studies that enroll women and infants at birth. Meconium holds promise as a biological matrix for measuring the intensity and duration of environmental toxicant exposure and future studies should validate the utility of meconium using other environmental toxicants.

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

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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 (psmokers. Nicotine and cotinine concentrations in hair clearly distinguished active from passive smokers.

Dermal uptake of nicotine from air and clothing: Experimental verification

DEFF Research Database (Denmark)

Bekö, Gabriel; Morrison, G.; Weschler, Charles J.

2017-01-01

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...

Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs.

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Xiao, Y; Smith, R D; Caruso, F S; Kellar, K J

2001-10-01

The opioid agonist properties of (+/-)-methadone are ascribed almost entirely to the (-)-methadone enantiomer. To extend our knowledge of the pharmacological actions of methadone at ligand-gated ion channels, we investigated the effects of the two enantiomers of methadone and its metabolites R-(+)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium perchlorate (EDDP) and R-(+)-2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline hydrochloride (EMDP), as well as structural analogs of methadone, including (-)-alpha-acetylmethadol hydrochloride (LAAM) and (+)-alpha-propoxyphene, on rat alpha3beta4 neuronal nicotinic acetylcholine receptors (nAChRs) stably expressed in a human embryonic kidney 293 cell line, designated KXalpha3beta4R2. (+/-)-methadone inhibited nicotine-stimulated 86Rb+ efflux from the cells in a concentration-dependent manner with an IC50 value of 1.9 +/- 0.2 microM, indicating that it is a potent nAChR antagonist. The (-)- and (+)-enantiomers of methadone have similar inhibitory potencies on nicotine-stimulated 86Rb+ efflux, with IC50 values of approximately 2 microM. EDDP, the major metabolite of methadone, is even more potent, with an IC50 value of approximately 0.5 microM, making it one of the most potent nicotinic receptor blockers reported. In the presence of (+/-)-methadone, EDDP, or LAAM, the maximum nicotine-stimulated 86Rb+ efflux was markedly decreased, but the EC50 value for nicotine stimulation was altered only slightly, if at all, indicating that these compounds block alpha3beta4 nicotinic receptor function by a noncompetitive mechanism. Consistent with a noncompetitive mechanism, (+/-)-methadone, its metabolites, and structural analogs have very low affinity for nicotinic receptor agonist binding sites in membrane homogenates from KXalpha3beta4R2 cells. We conclude that both enantiomers of methadone and its metabolites as well as LAAM and (+)-alpha-propoxyphene are potent noncompetitive antagonists of alpha3beta4 nAChRs.

Measurement of urinary Benzo[a]pyrene tetrols and their relationship to other polycyclic aromatic hydrocarbon metabolites and cotinine in humans.

Science.gov (United States)

Hilton, Donald C; Trinidad, Debra A; Hubbard, Kendra; Li, Zheng; Sjödin, Andreas

2017-12-01

Biomonitoring of exposure to polycyclic aromatic hydrocarbons (PAHs) typically uses measurement of metabolites of PAHs with four or less aromatic rings, such as 1-hydroxypyrene, even though interest may be in exposure to larger and carcinogenic PAHs, such as benzo[a]pyrene (B[a]P). An improved procedure for measuring two tetrol metabolites of B[a]P has been developed. Using 2 mL urine, the method includes enzymatic deconjugation of the tetrol conjugates, liquid-liquid extraction, activated carbon solid phase extraction (SPE) and Strata-X SPE, and gas chromatography-electron capture negative ionization-tandem mass spectrometric determination. Limits of detection were 0.026 pg/mL (benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, BPT I-1) and 0.090 pg/mL (benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol, BPT II-1). We quantified BPT I-1 and BPT II-1 in urine from a volunteer who consumed one meal containing high levels of PAHs (barbequed chicken). We also measured urinary concentrations of BPT I-1 and BPT II-1 in smokers and nonsmokers, and compared these concentrations with those of monohydroxy PAHs (OH-PAHs) and cotinine. Urinary elimination of BPT I-1 and BPT II-1 as a function of time after dietary exposure was similar to that observed previously for OH-PAHs. While the median BPT I-1 concentration in smokers' urine (0.069 pg/mL) significantly differs from nonsmokers (0.043 pg/mL), BPT I-1 is only weakly correlated with cotinine. The urinary concentration of BPT I-1 shows a weaker relationship to tobacco smoke than metabolites of smaller PAHs, suggesting that other routes of exposure such as for example dietary routes may be of larger quantitative importance. Published by Elsevier Ltd.

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

Energy Technology Data Exchange (ETDEWEB)

Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.; Hinderliter, Paul M.; Gunawan, Rudy; Timchalk, Charles

2013-02-01

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 development 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.

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

Science.gov (United States)

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

Carbamazepine but not valproate induces CYP2A6 activity in smokers with mental illness

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Williams, Jill M; Gandhi, Kunal K; Benowitz, Neal L

2010-01-01

BACKGROUND Anti-epileptic drugs (AED) are increasingly used in the management of serious mental illness yet their effects on nicotine metabolism have not been studied. METHODS This study investigated the effects of 3 AED (carbamazepine, CBZ; oxcarbazepine, OCB or valproic acid, VPA) on nicotine and nicotine metabolite levels in 149 smokers with schizophrenia and bipolar disorder who participated in an afternoon blood draw for nicotine, cotinine, and 3’-hydroxycotinine (3HC). The ratio of 3HC to cotinine was calculated as a marker of CYP2A6 metabolic activity. Eight smokers were taking CBZ, six were taking OCB and 40 were taking VPA. RESULTS The 3HC/cotinine ratio was significantly higher in individuals taking CBZ or OCB (combined, n=14) vs. those not taking it (mean 0.993 vs. 0.503; p< 0.001). The cotinine/cigarette per day ratio was significantly lower in individuals taking CBZ or OCB. The 3HC/cotinine ratios were also significantly higher in the subgroup of individuals taking CBZ (n=8) vs. those not taking it. There were no significant differences in nicotine or cotinine levels or 3HC/cotinine ratios in individuals taking VPA vs. those not taking it. We conducted backward stepwise linear regression models to identify predictors of the log transformed 3HC/cotinine ratios. Taking CBZ and number of cigarettes smoked per day were significant determinants of log 3HC/Cotinine. CONCLUSIONS CBZ likely induces hepatic metabolism via CYP2A6 and is associated with increased 3HC/Cotinine ratios. IMPACT Increased nicotine metabolism in individuals using AED has implications for increased smoking behavior and exposure to more tobacco toxins that warrants further study. PMID:20719908

Cigarettes with different nicotine levels affect sensory perception and levels of biomarkers of exposure in adult smokers.

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McKinney, Diana L; Frost-Pineda, Kimberly; Oldham, Michael J; Fisher, Michael T; Wang, Jingzhu; Gogova, Maria; Kobal, Gerd

2014-07-01

Few clinical studies involving cigarettes have provided a comprehensive picture of smoke exposure, test article characterization, and insights into sensory properties combined. The purpose of these pilot studies was to determine whether cigarettes with different levels of nicotine but similar tar levels would affect sensory experience or smoking behavior so as to significantly alter levels of selected biomarkers of exposure (BOE). In 2 confined, double-blind studies, 120 adult smokers switched from Marlboro Gold cigarettes at baseline to either 1 of 2 lower nicotine cigarettes or 1 of 2 higher nicotine cigarettes and then to the other cigarette after 5 days. Urinary excretion of exposure biomarkers (nicotine equivalents [NE], total and free 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL], 1-hydroxypyrene, and 3-hydroxypropyl mercapturic acid) as well as carboxyhemoglobin and plasma cotinine were measured at baseline, Day 5, and Day 10. Daily cigarette consumption was monitored and sensory characteristics were rated for each cigarette. With higher nicotine yield, urine NE, urine total NNAL, and plasma cotinine increased while nonnicotine BOE decreased without changes in cigarette consumption. In contrast, with lower nicotine yield, urine NE, urine total NNAL, and plasma cotinine dropped while nonnicotine BOE and cigarettes per day increased. Higher nicotine cigarettes were rated harsher and stronger than at baseline while lower nicotine cigarettes were less strong. All 4 test cigarettes were highly disliked. These studies demonstrate that abrupt increases or decreases in nicotine and the resulting sensory changes impact BOE through changes in intensity or frequency of 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.

Electronic cigarettes and nicotine clinical pharmacology.

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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

Science.gov (United States)

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

The impact of nicotine on bone healing and osseointegration

DEFF Research Database (Denmark)

Balatsouka, Dimitra; Gotfredsen, Klaus; Lindh, Christian H

2005-01-01

OBJECTIVES: To examine the short-term effect of nicotine on bone healing and osseointegration. MATERIAL AND METHODS: Sixteen female rabbits were divided into two groups. The test group was exposed to nicotine tartrate for 8 weeks and the control group was exposed to placebo. Nicotine or placebo...... was administered via a miniosmotic pump and plasma cotinine levels were measured weekly. The pump delivered 15 mg of nicotine/day for the animals in the test group. All rabbits had three tibial bone preparations. In the proximal and distal bone bed, implants were placed after 4 weeks (right tibia) and after 6...... and the control group. CONCLUSION: Nicotine exposure in a short period of time did not have a significant impact on bone healing or implant osseointegration in rabbits....

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

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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

Biomarkers of Tobacco Smoke Exposure in Racial/Ethnic Groups at High Risk for Lung Cancer

Science.gov (United States)

Moolchan, Eric T.; Pokhrel, Pallav; Herzog, Thaddeus; Cassel, Kevin D.; Pagano, Ian; Franke, Adrian A.; Kaholokula, Joseph Keawe’aimoku; Sy, Angela; Alexander, Linda A.; Trinidad, Dennis R.; Sakuma, Kari-Lyn; Johnson, C. Anderson; Antonio, Alyssa; Jorgensen, Dorothy; Lynch, Tania; Kawamoto, Crissy; Clanton, Mark S.

2015-01-01

Objectives. We examined biomarkers of tobacco smoke exposure among Native Hawaiians, Filipinos, and Whites, groups that have different lung cancer risk. Methods. We collected survey data and height, weight, saliva, and carbon monoxide (CO) levels from a sample of daily smokers aged 18–35 (n = 179). Mean measures of nicotine, cotinine, cotinine/cigarettes per day ratio, trans 3′ hydroxycotinine, the nicotine metabolite ratio (NMR), and expired CO were compared among racial/ethnic groups. Results. The geometric means for cotinine, the cotinine/cigarettes per day ratio, and CO did not significantly differ among racial/ethnic groups in the adjusted models. After adjusting for gender, body mass index, menthol smoking, Hispanic ethnicity, and number of cigarettes smoked per day, the NMR was significantly higher among Whites than among Native Hawaiians and Filipinos (NMR = 0.33, 0.20, 0.19, P ≤ .001). The NMR increased with increasing White parental ancestry. The NMR was not significantly correlated with social–environmental stressors. Conclusions. Racial/ethnic groups with higher rates of lung cancer had slower nicotine metabolism than Whites. The complex relationship between lung cancer risk and nicotine metabolism among racial/ethnic groups needs further clarification. PMID:25880962

Pharmacokinetics of cotinine in rats: a potential therapeutic agent for disorders of cognitive function.

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Li, Pei; Beck, Wayne D; Callahan, Patrick M; Terry, Alvin V; Bartlett, Michael G

2015-06-01

Attention has been paid to cotinine (COT), one of the major metabolites of nicotine (NIC), for its pro-cognitive effects and potential therapeutic activities against Alzheimer's disease (AD) and other types of cognitive impairment. In order to facilitate pharmacological and toxicological studies on COT for its pro-cognitive activities, we conducted a pharmacokinetic (PK) study of COT in rats, providing important oral and intravenously (iv) PK information. In this study, plasma samples were obtained up to 48 h after COT was dosed to rats orally and iv at a dose of 3mg/kg. Plasma samples were prepared and analyzed using a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalytical method, providing concentration profiles of COT and metabolites after oral and iv administrations. The data were fitted into a one-compartment model and a two-compartment model for the oral and iv groups, respectively, providing important PK information for COT including PK profiles, half-life, clearance and bioavailability. The results suggested fast absorption, slow elimination and high bioavailability of COT in rats. Several important facts about the PK properties in rats suggested COT could be a potential pro-cognitive agent. Information about the pharmacokinetics of COT in rats revealed in this study is of great importance for the future studies on COT or potential COT analogs as agents for improving cognition. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Regular nicotine intake increased tooth movement velocity, osteoclastogenesis and orthodontically induced dental root resorptions in a rat model

Science.gov (United States)

Kirschneck, Christian; Maurer, Michael; Wolf, Michael; Reicheneder, Claudia; Proff, Peter

2017-01-01

Orthodontic forces have been reported to significantly increase nicotine-induced periodontal bone loss. At present, however, it is unknown, which further (side) effects can be expected during orthodontic treatment at a nicotine exposure corresponding to that of an average European smoker. 63 male Fischer344 rats were randomized in three consecutive experiments of 21 animals each (A/B/C) to 3 experimental groups (7 rats, 1/2/3): (A) cone-beam-computed tomography (CBCT); (B) histology/serology; (C) reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR)/cotinine serology—(1) control; (2) orthodontic tooth movement (OTM) of the first and second upper left molar (NiTi closed coil spring, 0.25 N); (3) OTM with 1.89 mg·kg−1 per day s.c. of L(−)-nicotine. After 14 days of OTM, serum cotinine and IL-6 concentration as well as orthodontically induced inflammatory root resorption (OIIRR), osteoclast activity (histology), orthodontic tooth movement velocity (CBCT, within 14 and 28 days of OTM) and relative gene expression of known inflammatory and osteoclast markers were quantified in the dental-periodontal tissue (RT–qPCR). Animals exposed to nicotine showed significantly heightened serum cotinine and IL-6 levels corresponding to those of regular European smokers. Both the extent of root resorption, osteoclast activity, orthodontic tooth movement and gene expression of inflammatory and osteoclast markers were significantly increased compared to controls with and without OTM under the influence of nicotine. We conclude that apart from increased periodontal bone loss, a progression of dental root resorption and accelerated orthodontic tooth movement are to be anticipated during orthodontic therapy, if nicotine consumption is present. Thus patients should be informed about these risks and the necessity of nicotine abstinence during treatment. PMID:28960194

Rapid detection of drug metabolites in latent fingermarks.

Science.gov (United States)

Hazarika, Pompi; Jickells, Sue M; Russell, David A

2009-01-01

Magnetic particles functionalised with anti-cotinine antibody have been used to image latent fingermarks through the detection of the cotinine antigen in the sweat deposited within the fingerprints of smokers. The antibody-magnetic particle conjugates are readily applied to latent fingerprints while excess reagents are removed through the use of a magnetic wand. The results have shown that drug metabolites, such as cotinine, can be detected and used to image the fingermark to establish the identity of an individual within 15 minutes.

Differences in Nicotine Metabolism of Two Nicotiana attenuata Herbivores Render Them Differentially Susceptible to a Common Native Predator

Science.gov (United States)

Kumar, Pavan; Rathi, Preeti; Schöttner, Matthias; Baldwin, Ian T.; Pandit, Sagar

2014-01-01

Background Nicotiana attenuata is attacked by larvae of both specialist (Manduca sexta) and generalist (Spodoptera exigua) lepidopteran herbivores in its native habitat. Nicotine is one of N. attenuata's important defenses. M. sexta is highly nicotine tolerant; whether cytochrome P450 (CYP)-mediated oxidative detoxification and/or rapid excretion is responsible for its exceptional tolerance remains unknown despite five decades of study. Recently, we demonstrated that M. sexta uses its nicotine-induced CYP6B46 to efflux midgut-nicotine into the hemolymph, facilitating nicotine exhalation that deters predatory wolf spiders (Camptocosa parallela). S. exigua's nicotine metabolism is uninvestigated. Methodology/Principal Findings We compared the ability of these two herbivores to metabolize, tolerate and co-opt ingested nicotine for defense against the wolf spider. In addition, we analyzed the spider's excretion to gain insights into its nicotine metabolism. Contrary to previous reports, we found that M. sexta larvae neither accumulate the common nicotine oxides (cotinine, cotinine N-oxide and nicotine N-oxide) nor excrete them faster than nicotine. In M. sexta larvae, ingestion of nicotine as well as its oxides increases the accumulation of CYP6B46 transcripts. In contrast, S. exigua accumulates nicotine oxides and exhales less (66%) nicotine than does M. sexta. Spiders prefer nicotine-fed S. exigua over M. sexta, a preference reversed by topical or headspace nicotine supplementation, but not ingested or topically-coated nicotine oxides, suggesting that externalized nicotine but not the nicotine detoxification products deter spider predation. The spiders also do not accumulate nicotine oxides. Conclusions Nicotine oxidation reduces S. exigua's headspace-nicotine and renders it more susceptible to predation by spiders than M. sexta, which exhales unmetabolized nicotine. These results are consistent with the hypothesis that generalist herbivores incur costs of

The association between self-reported versus nicotine metabolite-confirmed smoking status and coronary artery calcification.

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Kim, Byung Jin; Han, Ji Min; Kang, Jung Gyu; Kim, Bum Soo; Kang, Jin Ho

2018-05-01

There are no data comparing the relationship between coronary artery calcification and self-reported and cotinine-verified smoking. This study was carried out to evaluate the relationship between coronary artery calcium (CAC) and urinary cotinine or self-reported smoking status in Korean adults. Study participants included 22 797 individuals (19 181 men; mean age±SD 39.2±7.1 years) who were enrolled in the Kangbuk Samsung Health Study and Kangbuk Samsung Cohort Study between 2011 and 2013, and who had urinary cotinine and CAC measurements. Cotinine-verified current smokers were defined as having a urinary cotinine level of above 50 ng/ml. The prevalence of never smokers, former smokers, and current smokers according to the self-reported questionnaires was 44.6, 24.2, and 31.2%, respectively, and that of cotinine-verified current smokers was 30.2%. The prevalence of the presence of CAC in self-reported current smokers was higher than that in self-reported never/former smokers (13.7 vs. 10.2%, P<0.001), and that in cotinine-verified current smokers was higher than that in cotinine-verified never smokers (14.0 vs. 10.2%, P<0.001). A multivariate logistic regression model adjusted for the variables with univariate relationships showed that self-reported former smokers and current smokers had significantly increased odds ratio (OR) for the presence of CAC compared with self-reported never smokers [OR (95% confidence interval): 1.20 (1.03-1.40) in former smokers and 1.29 (1.11-1.50) in current smokers]. Cotinine-verified current smokers also showed a significant association with the presence of CAC [1.23 (1.12-1.35)]. Furthermore, log-transformed cotinine levels increased the OR for the presence of CAC [1.03 (1.01-1.05)]. This study is the first large cohort study to show that both self-reported and cotinine-verified smoking is associated independently with the presence of CAC in Korean adults.

Biotransformation of primary nicotine metabolites. I. In vivo metabolism of R-(+)-[14C-NCH3]N-methylnicotinium ion in the guinea pig

International Nuclear Information System (INIS)

Pool, W.F.; Crooks, P.A.

1985-01-01

The in vivo biotransformation and tissue distribution of the methylated nicotine metabolite R-(+)-[ 14 C-NCH 3 ]N-methylnicotinium acetate was studied in the guinea pig. The detection and quantification of 24-hr urinary metabolites after ip injection was determined by cation-exchange HPLC interfaced to a radiochemical flowthrough detector. The urinary metabolite profile consisted of five peaks. One eluted close to the void, and three coeluted with authentic standards of N-methylcotininium ion, N-methylnornicotinium ion, and N-methylnicotinium ion. A fifth, and as yet unidentified, metabolite was also detected. Tissue distribution of 14 C label after 24 hr was highest in the adrenal gland and epididymis followed by the gallbladder, bladder, kidney, spleen, and heart. No significant amounts of 14 C were found in the brain. The results indicate that N-methylcotininium ion and N-methylnornicotinium ion are both formed subsequent to the formation of N-methylnicotinium ion in the metabolism of R-(+)-nicotine in the guinea pig

Biodegradation of nicotine by a novel nicotine-degrading bacterium, Pseudomonas plecoglossicida TND35 and its new biotransformation intermediates.

Science.gov (United States)

Raman, Gurusamy; Mohan, KasiNadar; Manohar, Venkat; Sakthivel, Natarajan

2014-02-01

Tobacco wastes that contain nicotine alkaloids are harmful to human health and the environment. In the investigation, a novel nicotine-biodegrading bacterium TND35 was isolated and identified as Pseudomonas plecoglossicida on the basis of phenotypic, biochemical characteristics and 16S rRNA sequence homology. We have studied the nicotine biodegradation potential of strain TND35 by detecting the intermediate metabolites using an array of approaches such as HPLC, GC-MS, NMR and FT-IR. Biotransformation metabolites, N-methylmyosmine, 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and other three new intermediate metabolites namely, 3,5-bis (1-methylpyrrolidin-2-yl) pyridine, 2,3-dihydro-1-methyl-5-(pyridin-3-yl)-1H-pyrrol-2-ol and 5-(pyridin-3-yl)-1H-pyrrol-2(3H)-one have been identified. Interestingly, these intermediate metabolites suggest that the strain TND35 employs a novel nicotine biodegradation pathway, which is different from the reported pathways of Aspergillus oryzae 112822, Arthrobacter nicotinovorans pAO1, Agrobacterium tumefaciens S33 and other species of Pseudomonas. The metabolite, HPB reported in this study can also be used as biochemical marker for tobacco related cancer studies.

Nicotine Dependence, Physical Activity, and Sedentary Behavior among Adult Smokers.

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Loprinzi, Paul D; Walker, Jerome F

2015-03-01

Research has previously demonstrated an inverse association between smoking status and physical activity; however, few studies have examined the association between nicotine dependence and physical activity or sedentary behavior. This study examined the association between nicotine dependence and accelerometer-determined physical activity and sedentary behavior. Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used. A total of 851 adult (≥20 years) smokers wore an accelerometer for ≥4 days and completed the Fagerstrom Test for Nicotine Dependence scale. Regression models were used to examine the association between nicotine dependence and physical activity/sedentary behavior. After adjusting for age, gender, race-ethnicity, poverty level, hypertension, emphysema, bronchitis, body mass index (BMI), cotinine, and accelerometer wear time, smokers 50 + years of age with greater nicotine dependence engaged in more sedentary behavior (β = 11.4, P = 0.02) and less light-intensity physical activity (β = -9.6, P = 0.03) and moderate-to-vigorous physical activity (MVPA; β = -0.14, P = 0.003) than their less nicotine dependent counterparts. Older adults who are more nicotine dependent engage in less physical activity (both MVPA and light-intensity) and more sedentary behavior than their less nicotine dependent counterparts.

The association between smoking and ectopic pregnancy: why nicotine is BAD for your fallopian tube.

Directory of Open Access Journals (Sweden)

Andrew W Horne

Full Text Available Epidemiological studies have shown that cigarette smoking is a major risk factor for tubal ectopic pregnancy but the reason for this remains unclear. Here, we set out to determine the effect of smoking on Fallopian tube gene expression. An oviductal epithelial cell line (OE-E6/E7 and explants of human Fallopian tubes from non-pregnant women (n = 6 were exposed to physiologically relevant concentrations of cotinine, the principle metabolite of nicotine, and changes in gene expression analyzed using the Illumina Human HT-12 array. Cotinine sensitive genes identified through this process were then localized and quantified in Fallopian tube biopsies from non-pregnant smokers (n = 10 and non-smokers (n = 11 using immunohistochemistry and TaqMan RT-PCR. The principle cotinine induced change in gene expression detected by the array analysis in both explants and the cell line was significant down regulation (P<0.05 of the pro-apoptotic gene BAD. We therefore assessed the effect of smoking on cell turnover in retrospectively collected human samples. Consistent with the array data, smoking was associated with decreased levels of BAD transcript (P<0.01 and increased levels of BCL2 transcript (P<0.05 in Fallopian tube biopsies. BAD and BCL2 specific immunolabelling was localized to Fallopian tube epithelium. Although no other significant differences in levels of apoptosis or cell cycle associated proteins were observed, smoking was associated with significant changes in the morphology of the Fallopian tube epithelium (P<0.05. These results suggest that smoking may alter tubal epithelial cell turnover and is associated with structural, as well as functional, changes that may contribute to the development of ectopic pregnancy.

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

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

2016-01-01

Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach 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). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 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. Conclusion and Implications 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. PMID:27667659

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

Energy Technology Data Exchange (ETDEWEB)

Saylor, Kyle, E-mail: saylor@vt.edu; Zhang, Chenming, E-mail: chzhang2@vt.edu

2016-09-15

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. - 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.

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

International Nuclear Information System (INIS)

Saylor, Kyle; Zhang, Chenming

2016-01-01

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. - 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.

Genome-wide association study of a nicotine metabolism biomarker in African American smokers: impact of chromosome 19 genetic influences.

Science.gov (United States)

Chenoweth, Meghan J; Ware, Jennifer J; Zhu, Andy Z X; Cole, Christopher B; Cox, Lisa Sanderson; Nollen, Nikki; Ahluwalia, Jasjit S; Benowitz, Neal L; Schnoll, Robert A; Hawk, Larry W; Cinciripini, Paul M; George, Tony P; Lerman, Caryn; Knight, Joanne; Tyndale, Rachel F

2018-03-01

The activity of CYP2A6, the major nicotine-inactivating enzyme, is measurable in smokers using the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine). Due to its role in nicotine clearance, the NMR is associated with smoking behaviours and response to pharmacotherapies. The NMR is highly heritable (~80%), and on average lower in African Americans (AA) versus whites. We previously identified several reduce and loss-of-function CYP2A6 variants common in individuals of African descent. Our current aim was to identify novel genetic influences on the NMR in AA smokers using genome-wide approaches. Genome-wide association study (GWAS). Multiple sites within Canada and the United States. AA smokers from two clinical trials: Pharmacogenetics of Nicotine Addiction Treatment (PNAT)-2 (NCT01314001; n = 504) and Kick-it-at-Swope (KIS)-3 (NCT00666978; n = 450). Genome-wide SNP genotyping, the NMR (phenotype) and population substructure and NMR covariates. Meta-analysis revealed three independent chromosome 19 signals (rs12459249, rs111645190 and rs185430475) associated with the NMR. The top overall hit, rs12459249 (P = 1.47e-39; beta = 0.59 per C (versus T) allele, SE = 0.045), located ~9.5 kb 3' of CYP2A6, remained genome-wide significant after controlling for the common (~10% in AA) non-functional CYP2A6*17 allele. In contrast, rs111645190 and rs185430475 were not genome-wide significant when controlling for CYP2A6*17. In total, 96 signals associated with the NMR were identified; many were not found in prior NMR GWASs in individuals of European descent. The top hits were also associated with the NMR in a third cohort of AA (KIS2; n = 480). None of the hits were in UGT or OCT2 genes. Three independent chromosome 19 signals account for ~20% of the variability in the nicotine metabolite ratio in African American smokers. The hits identified may contribute to inter-ethnic variability in nicotine metabolism, smoking behaviours and tobacco-related disease risk

Does longstanding nicotine exposure impair bone healing and osseointegration? An experimental study in rabbits

DEFF Research Database (Denmark)

Gotfredsen, Klaus; Lindh, Christian H; Berglundh, Tord

2009-01-01

OBJECTIVES: The aim of this study was to analyze the effect of longstanding nicotine exposure on bone healing and osseointegration of titanium implants. MATERIALS AND METHODS: 20 female rabbits received either nicotine (n = 10) or saline (n = 10) administered subcutaneously via mini-osmotic pumps...... for 32 weeks. The pump delivered 6 microg/kg/min of nicotine for the animals in the test group. Blood samples were collected and plasma cotinine levels were measured monthly. Six months after the commencement of nicotine or saline administration three osteotomy preparations, one in right, femoral condyle...... increase in RMT between 2 and 4 weeks within each group. The histomorphometric analysis of bone-to-implant contact and bone density in the bone defects revealed no differences between the test and the control group after 2 or 4 weeks of healing. CONCLUSION: Longstanding (6 months) nicotine exposure did...

Evaluating nicotine dependence levels in e-cigarette users.

Science.gov (United States)

González Roz, Alba; Secades Villa, Roberto; Weidberg, Sara

2017-01-11

Despite the fact that electronic cigarettes (e-cigarettes) are rapidly growing in popularity and use worldwide, there is scarce scientific data on abuse liability among e-cigarette users, and about whether e-cigarette use is related to nicotine dependence or not. The aim of this study is to explore nicotine dependence levels in a sample of experienced e-cigarette users (n= 39) and to compare them with current tobacco cigarette smokers (n=42). We conducted several face-to-face interviews in order to assess sociodemographic and dependence related characteristics in both e-cigarette users and in smokers. Adapted versions of both the Fagerström test for nicotine dependence (FTND) and the nicotine dependence syndrome scale (NDSS) were used to analyze nicotine dependence in each of the groups. Biochemical markers of carbon monoxide and urinary cotinine analysis were also collected. Results showed that e-cigarette users scored lower than cigarette smokers in both FTND and all NDSS subscales. Our findings extend previous research on e-cigarette use and nicotine addiction and suggest that e-cigarette users are less dependent on nicotine than current tobacco cigarette smokers. Further prospective studies are needed to better ascertain their addictiveness potential, comparing those smokers who switched to e-cigarettes from smoking cigarettes, and those who had never been tobacco cigarette smokers.

Gutkha Addiction: Nicotine Dependence or a Conditioned Reflex?

OpenAIRE

Joshi, Prathamesh Satish; Prashant, M C; Nagpal, Neelu; Patil, Atulkumar A; Ahuja, Rinky; Mathur, Vidhi

2015-01-01

Background: A pre-packaged mixture of areca nut, tobacco, slaked lime, catechu, and flavoring agents is popularly known as Gutkha. Aim of study is to analyze the addiction biology of Gutkha chewing and to assess efficacy of a cessation program based on nicotine replacement therapy (NRT). Materials and Methods: Patterns of addiction of 400 Gutkha chewers were analyzed with a questionnaire-based survey. Urine cotinine levels of 60 subjects undergoing NRT were periodically estimated using gas ch...

Waste-indicator and pharmaceutical compounds in landfill-leachate-affected ground water near Elkhart, Indiana, 2000-2002.

Science.gov (United States)

Buszka, P M; Yeskis, D J; Kolpin, D W; Furlong, E T; Zaugg, S D; Meyer, M T

2009-06-01

Four wells downgradient from a landfill near Elkhart, Indiana were sampled during 2000-2002 to evaluate the presence of waste-indicator and pharmaceutical compounds in landfill-leachate-affected ground water. Compounds detected in leachate-affected ground water included detergent metabolites (p-nonylphenol, nonylphenol monoethoxylate, nonylphenol diethoxylate, and octylphenol monoethoxylate), plasticizers (ethanol-2-butoxy-phosphate and diethylphthalate), a plastic monomer (bisphenol A), disinfectants (1,4-dichlorobenzene and triclosan), an antioxidant (5-methyl-1H-benzotriazole), three fire-retardant compounds (tributylphosphate and tri(2-chloroethyl)phosphate, and tri(dichlorisopropyl)phosphate), and several pharmaceuticals and metabolites (acetaminophen, caffeine, cotinine, 1,7-dimethylxanthine, fluoxetine, and ibuprofen). Acetaminophen, caffeine, and cotinine detections confirm prior indications of pharmaceutical and nicotinate disposal in the landfill.

Racial Differences in Serum Cotinine Levels of Smokers

Directory of Open Access Journals (Sweden)

Lisa B. Signorello

2009-01-01

Full Text Available The purpose of this study was to estimate black/white differences in cotinine levels for current smokers of both sexes, and to explore the potential contribution of mentholated cigarettes to these differences. Sera from 255 current smokers sampled from Southern Community Cohort Study participants (65 black men, 65 black women, 63 white men, 62 white women were analyzed for cotinine, and linear regression was used to model the effect of race on cotinine level, adjusting for the number of cigarettes smoked within the last 24 hours, use of menthol vs. non-menthol cigarettes, exposure to environmental tobacco smoke, and age. Black smokers smoked fewer cigarettes than white smokers, yet had crude mean cotinine levels nearly as high or higher than white smokers. After multivariate adjustment, cotinine levels were an average of 50 ng/ml higher among black than white women (p=0.008 and non-significantly 12 ng/ml higher among black than white men (p=0.52. We observed no increase in cotinine levels associated with menthol cigarette use. We conclude that differences in cotinine levels among smokers suggest racial variation in exposure to and/or metabolism of tobacco smoke constituents, but our findings do not support a role for menthol preference in this disparity.

Racial differences in serum cotinine levels of smokers.

Science.gov (United States)

Signorello, Lisa B; Cai, Qiuyin; Tarone, Robert E; McLaughlin, Joseph K; Blot, William J

2009-01-01

The purpose of this study was to estimate black/white differences in cotinine levels for current smokers of both sexes, and to explore the potential contribution of mentholated cigarettes to these differences. Sera from 255 current smokers sampled from Southern Community Cohort Study participants (65 black men, 65 black women, 63 white men, 62 white women) were analyzed for cotinine, and linear regression was used to model the effect of race on cotinine level, adjusting for the number of cigarettes smoked within the last 24 hours, use of menthol vs. non-menthol cigarettes, exposure to environmental tobacco smoke, and age. Black smokers smoked fewer cigarettes than white smokers, yet had crude mean cotinine levels nearly as high or higher than white smokers. After multivariate adjustment, cotinine levels were an average of 50 ng/ml higher among black than white women (p=0.008) and non-significantly 12 ng/ml higher among black than white men (p=0.52). We observed no increase in cotinine levels associated with menthol cigarette use. We conclude that differences in cotinine levels among smokers suggest racial variation in exposure to and/or metabolism of tobacco smoke constituents, but our findings do not support a role for menthol preference in this disparity.

The effects of subcutaneous injection of nicotine on osseointegration of machined and anodized implants in rabbits.

Science.gov (United States)

Linden, Maria Salete Sandini; Bittencourt, Marcos Eugênio de; Carli, João Paulo De; Miyagaki, Daniela Cristina; Santos, Pâmela Letícia Dos; Paranhos, Luiz Renato; Groppo, Francisco Carlos; Ramacciato, Juliana Cama

2018-01-01

To evaluate the influence of subcutaneous injection nicotine in osseointegration process on different implant surfaces. Twenty-two male rabbits were distributed into two groups according to the subcutaneous injections: (1) nicotine 3 mg/day/kg and (2) 0.9 % NaCI 3 mL/day/kg, three times a day; subgroups were then designated-machined and anodized implants were placed in the right and left tibia bones, respectively. The animals were submitted euthanasia after periods of eight weeks to determine nicotine and cotinine levels, alkaline phosphatase and biomechanical analysis. The plasmatic levels of nicotine and cotinine were 0.5 ± 0.28 ng/mL and 9.5 ± 6.51 ng/mL, respectively. The alkaline phosphatase analyses in blood levels in control group were observed 40.8 ± 11.88 UI/L and 40.75 ± 12.46 UI/L, for the surfaces machined and anodized, respectively. In the test group was observed levels 37.9 ± 4.84 UI/L, for both implant surfaces. No significant differences were observed between control and test groups and between the implant surfaces regarding alkaline phosphatase blood levels. For biomechanics, no significant differences were observed in control group between the machined (25±8.46 Ncm) or anodized (31.2 ± 6.76 Ncm) implants. However, the treatment with nicotine induced higher torque than control in both machined (38.3 ± 13.52 Ncm) and anodized (35.5 ± 14.17 Ncm) implants, with p = 0.0024 and p = 0.0121, respectively. Subcutaneous injection of nicotine following implant insertion didn't have effect on osseointegration, independently from the implant surface.

Successful Nicotine Intake in Medical Assisted Use of E-Cigarettes: A Pilot Study.

Science.gov (United States)

Pacifici, Roberta; Pichini, Simona; Graziano, Silvia; Pellegrini, Manuela; Massaro, Giuseppina; Beatrice, Fabio

2015-07-08

The electronic cigarette (e-cig) has gained popularity as an aid in smoking cessation programs mainly because it maintains the gestures and rituals of tobacco smoking. However, it has been shown in inexperienced e-cig users that ineffective nicotine delivery can cause tobacco craving that could be responsible for unsuccessful smoking reduction/cessation. Moreover, the incorrect use of an e-cig could also led to potential nicotine overdosage and intoxication. Medically assisted training on the proper use of an e-cig plus behavioral support for tobacco dependence could be a pivotal step in avoiding both issues. We performed an eight-month pilot study of adult smokers who started e-cig use after receiving a multi-component medically assisted training program with monitoring of nicotine intake as a biomarker of correct e-cig use. Participants were tested during follow-up for breath carbon monoxide (CO), plasma cotinine and trans-3'-hydroxycotinine, and number of tobacco cigarettes smoked. At the end of the first, fourth, and eighth month of follow-up, 91.1, 73.5, and 76.5% of participants respectively were e-cig users ('only e-cig' and 'dual users'). They showed no significant variation in plasma cotinine and trans-3'-hydroxycotinine with respect to the start of the study when they smoked only tobacco cigarettes, but a significant reduction in breath CO. The proposed medically assisted training program of e-cig use led to a successful nicotine intake, lack of typical cigarette craving and overdosage symptoms and a significant decrease in the biomarker of cigarette combustion products.

Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.

Directory of Open Access Journals (Sweden)

Andrew W Bergen

Full Text Available The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine, has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3. Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis.

Activators of plasminogen and the progression of small abdominal aortic aneurysms

DEFF Research Database (Denmark)

Lindholt, Jes Sanddal

2006-01-01

), macrophage-inhibiting factor (MIF), transforming-growth-factor-beta1 (TGF-beta1), homocysteine, and serum levels of IgA-antibodies against Chlamydia pneumoniae (IgA-CP) and cotinine (a nicotine metabolite) were measured. The annual expansion rate correlated positively with tPA, IgA-CP, and S-cotinine; rho...... = 0.37 (P = 0.004), 0.28 (P = 0.01), and 0.24 (P = 0.04), while PAI-1, uPA, TGF-beta1, homocysteine, and MIF did not. S-cotinine and PAI-1 also correlated positively with tPA, rho = 0.24 (P = 0.04), and 0.33 (P = 0.005). IgA-CP did not correlate with tPA. By receiver operating characteristics (ROC...

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

Science.gov (United States)

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.

Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy

Science.gov (United States)

Grangé, Gilles; Jacob, Nelly; Tanguy, Marie-Laure

2014-01-01

Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day). Design Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013. Setting 23 maternity wards in France. Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group. Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support. Main outcome measures The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis. Results Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self

Evaluation of different smoking habits during music festivals through wastewater analysis.

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Mackuľak, Tomáš; Grabic, Roman; Gál, Marián; Gál, Miroslav; Birošová, Lucia; Bodík, Igor

2015-11-01

Wastewater analysis is a powerful method that can provide useful information about the abuse of legal and illicit drugs. The aim of our study was to determine nicotine consumption during four different music festivals and to find a connection between smoking and preferences for specific music styles using wastewater analysis. The amount of the nicotine metabolite cotinine was monitored in wastewater at the influent of three waste water treatment plants WWTPs in the Czech Republic and Slovakia, where the festivals took place. Urinary bio-markers of nicotine utilization were analyzed by LC-HRMS. More than 80,000 festival participants were monitored during our study from June to September 2014. A significant increase of nicotine consumption was observed in wastewaters during music festivals. The nicotine ingestion level was back-calculated and expressed as mass of pure drug consumed per day and per 1000 inhabitants for selected cities of both countries. The highest differences between typical levels of cotinine in wastewaters and the levels during music festivals were detected in Piešťany: 4 g/L/1000 inhabitants during non-festival days compared to 8 g/L/1000 inhabitants during the Topfest pop-rock festival and 6g/L/1000 inhabitants during the Grape dance festival. No significant increase of the amounts of cotinine in wastewater was recorded for the Country and Folk festivals. Copyright © 2015 Elsevier B.V. All rights reserved.

Smoking cessation is followed by a sharp but transient rise in the incidence of overt autoimmune hypothyroidism – A population‐based, case–control study

DEFF Research Database (Denmark)

Carlé, Allan; Bülow Pedersen, Inge; Knudsen, Nils

2012-01-01

habits were verified by measuring urinary cotinine (a nicotine metabolite). Incident hypothyroidism was very common in people who had recently stopped smoking: OR vs never smokers (95%‐CI); quit smoking 10 years, 0·76 (0·38–1·51). Results were consistent in both sexes and irrespective of age. Within two...

Successful Nicotine Intake in Medical Assisted Use of E-Cigarettes: A Pilot Study

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Roberta Pacifici

2015-07-01

Full Text Available The electronic cigarette (e-cig has gained popularity as an aid in smoking cessation programs mainly because it maintains the gestures and rituals of tobacco smoking. However, it has been shown in inexperienced e-cig users that ineffective nicotine delivery can cause tobacco craving that could be responsible for unsuccessful smoking reduction/cessation. Moreover, the incorrect use of an e-cig could also led to potential nicotine overdosage and intoxication. Medically assisted training on the proper use of an e-cig plus behavioral support for tobacco dependence could be a pivotal step in avoiding both issues. We performed an eight-month pilot study of adult smokers who started e-cig use after receiving a multi-component medically assisted training program with monitoring of nicotine intake as a biomarker of correct e-cig use. Participants were tested during follow-up for breath carbon monoxide (CO, plasma cotinine and trans-3’-hydroxycotinine, and number of tobacco cigarettes smoked. At the end of the first, fourth, and eighth month of follow-up, 91.1, 73.5, and 76.5% of participants respectively were e-cig users (‘only e-cig’ and ‘dual users’. They showed no significant variation in plasma cotinine and trans-3’-hydroxycotinine with respect to the start of the study when they smoked only tobacco cigarettes, but a significant reduction in breath CO. The proposed medically assisted training program of e-cig use led to a successful nicotine intake, lack of typical cigarette craving and overdosage symptoms and a significant decrease in the biomarker of cigarette combustion products.

The impact of nicotine on osseointegration. An experimental study in the femur and tibia of rabbits

DEFF Research Database (Denmark)

Balatsouka, Dimitra; Gotfredsen, Klaus; Lindh, Christian H

2005-01-01

OBJECTIVES: The aim of the present study was to analyze the effect of an enhanced systematic dose of nicotine on osseointegration of titanium implants. MATERIAL AND METHODS: Sixteen female rabbits received either nicotine (n=8) or saline (n=8) administered subcutaneously via mini-osmotic pumps...... for 2 months. The pump delivered 6 mug/kg/min of nicotine for the animals in the test group. Blood was withdrawn and plasma cotinine levels were measured weekly. Thirty-two titanium implants were inserted into the femur and tibia of all rabbits after 4 weeks and after 6 weeks of nicotine...... and the peri-implant BD-i showed no significant differences between the test and the control group after 2 or after 4 weeks. CONCLUSION: Nicotine exposure for a short period of time even in a high dose did not have a significant impact on implant osseointegration in rabbits....

Serum Cotinine Levels and Prehypertension in Never Smokers

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Omayma Alshaarawy

2013-01-01

Full Text Available Background. Few studies have shown that self-reported secondhand smoke exposure in never smokers is associated with high blood pressure. However, there are no studies investigating the relationship between secondhand smoke exposure, measured objectively by serum cotinine levels, and high blood pressure in never smokers. Methods. We examined never smokers (n=2027 from the National Health and Nutrition Examination Survey 2005–2008. Our exposure of interest was the secondhand smoke exposure estimated by serum cotinine level and our outcome was prehypertension (n=734, defined as a systolic blood pressure of 120–139 mmHg or diastolic blood pressure of 80–89 mmHg. Results. We found that, in never smokers, serum cotinine levels were positively associated with prehypertension. Compared to those with cotinine levels in the lowest quartile (≤0.024 ng/mL, the multivariable odds ratio (95% confidence interval of prehypertension among those with cotinine levels in the highest quartile (≥0.224 ng/mL was 1.45(1.00, 2.11; P trend =0.0451. In subsequent subgroup analyses, the positive association was found to be stronger among men, non-Whites, and non-obese subjects. Conclusion. Higher secondhand smoke exposure measured objectively by serum cotinine levels was found to be associated with prehypertension in certain subgroups of a representative sample of the US population.

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

Energy Technology Data Exchange (ETDEWEB)

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

1984-09-01

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. During 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.

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

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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

Comparison of serum cotinine concentration within and across smokers of menthol and nonmenthol cigarette brands among non-Hispanic black and non-Hispanic white U.S. adult smokers, 2001-2006.

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Caraballo, Ralph S; Holiday, David B; Stellman, Steven D; Mowery, Paul D; Giovino, Gary A; Muscat, Joshua E; Eriksen, Michael P; Bernert, John T; Richter, Patricia A; Kozlowski, Lynn T

2011-07-01

The Food and Drug Administration (FDA) is examining options for regulating menthol content in cigarettes. There are many pharmacologic properties of menthol that may facilitate exposure to tobacco smoke, and it has been suggested that the preference for menthol cigarettes in black smokers accounts for their higher cotinine levels. To assess cigarettes smoked per day-adjusted cotinine levels in relation to smoking a menthol or nonmenthol cigarette brand among non-Hispanic black and white U.S. adult smokers under natural smoking conditions. Serum cotinine concentrations were measured in 1,943 smokers participating in the 2001 to 2006 National Health and Nutrition Examination Surveys (NHANES). The effect of smoking a menthol brand on cigarettes smoked per day-adjusted serum cotinine levels in these two populations was modeled by adjusting for sex, age, number of smokers living in the home, body weight, time since last smoked, and FTC (Federal Trade Commission)-measured nicotine levels. The 8- or 12-digit Universal Product Code (UPC) on the cigarette label was used to determine the cigarette brand and whether it was menthol. Smoking a menthol cigarette brand versus smoking a nonmenthol cigarette brand was not associated (P ≥ 0.05) with mean serum cotinine concentration in either black or white smokers. The higher levels of cotinine observed in black smokers compared with white smokers are not explained by their higher preference for menthol cigarette brands. Further studies like ours are needed to improve our ability to understand health consequences of future changes in tobacco product design. ©2011 AACR

Environmental tobacco smoke and canine urinary cotinine level

International Nuclear Information System (INIS)

Bertone-Johnson, Elizabeth R.; Procter-Gray, Elizabeth; Gollenberg, Audra L.; Ryan, Michele B.; Barber, Lisa G.

2008-01-01

Epidemiologic studies of companion animals such as dogs have been established as models for the relationship between exposure to environmental tobacco smoke (ETS) and cancer risk in humans. While results from these studies are provocative, pet owner report of a dog's ETS exposure has not yet been validated. We have evaluated the relationship between dog owner's report of household smoking by questionnaire and dog's urinary cotinine level. Between January and October 2005, dog owners presenting their pet for non-emergency veterinary care at the Foster Hospital for Small Animals at Cummings School of Veterinary Medicine, Tufts University, were asked to complete a 10-page questionnaire measuring exposure to household ETS in the previous 24 h and other factors. A free-catch urine sample was also collected from dogs. Urinary cotinine level was assayed for 63 dogs, including 30 whose owners reported household smoking and 33 unexposed dogs matched on age and month of enrollment. Urinary cotinine level was significantly higher in dogs exposed to household smoking in the 24 h before urine collection compared to unexposed dogs (14.6 ng/ml vs. 7.4 ng/ml; P=0.02). After adjustment for other factors, cotinine level increased linearly with number of cigarettes smoked by all household members (P=0.004). Other canine characteristics including age, body composition and nose length were also associated with cotinine level. Findings from our study suggest that household smoking levels as assessed by questionnaire are significantly associated with canine cotinine levels

Intolerance for smoking abstinence among nicotine-deprived, treatment-seeking smokers.

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Germeroth, Lisa J; Baker, Nathaniel L; Saladin, Michael E

2018-09-01

The Intolerance for Smoking Abstinence Discomfort Questionnaire (IDQ-S) assesses distress tolerance specific to nicotine withdrawal. Though developed to assess withdrawal-related distress, the IDQ-S has not been validated among nicotine-deprived, treatment-seeking smokers. The present study extended previous research by examining the predictive utility of the IDQ-S among abstinent, motivated-to-quit smokers. Abstinent, treatment-seeking smokers completed the IDQ-S Withdrawal Intolerance and Lack of Cognitive Coping scales, assessments of nicotine dependence and reinforcement, and smoking history at baseline. At baseline and at 24-h, 2-week, and 1-month follow-up, participants completed a smoking cue-reactivity task (collection of cue-elicited craving and negative affect), and assessments of cigarettes per day (CPD; daily diaries at follow-up), carbon monoxide (CO), and cotinine. Greater IDQ-S Withdrawal Intolerance was associated with younger age, higher nicotine dependence and reinforcement, and less smoking years (ps  .10). Withdrawal intolerance and lack of cognitive coping did not predict smoking outcomes among nicotine-deprived, treatment-seeking smokers, but were associated with smoking characteristics, including nicotine dependence and reinforcement. Withdrawal intolerance and lack of cognitive coping may not be especially useful in predicting craving and smoking behavior, but future studies should replicate the present study's findings and assess the stability of the IDQ-S before forming firm conclusions about its predictive utility. Copyright © 2018 Elsevier Ltd. All rights reserved.

Salivary cotinine levels as a biomarker for green tobacco sickness in dry tobacco production among Thai traditional tobacco farmers.

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Saleeon, Thanusin; Siriwong, Wattasit; Maldonado-Pérez, Héctor Luis; Robson, Mark Gregory

2016-01-01

Dry Thai traditional tobacco (Nicotiana Tabacum L.) production involves a unique process: (a) picking tobacco leaves, (b) curing tobacco leaves, (c) removing stems of tobacco leaves, cutting leaves and putting on a bamboo rack, (d) drying in the sun, reversing a rack, spraying a tobacco extract to adjust the tobacco's color, storing dried tobacco and packaging. These processes may lead to adverse health effects caused by dermal absorption of nicotine such as Green Tobacco Sickness (GTS). The aim of this study was to determine the correlation between GTS resulting from dry Thai traditional tobacco production and salivary cotinine levels among Thai traditional tobacco farmers in Nan Province, Thailand. A prospective cohort study was conducted with 20 tobacco farmers and 20 non-tobacco farmers in Praputtabath Sub-District and Phatow Sub-District. The participants were randomly selected and interviewed using in person questionnaires with bi-weekly follow-up for 14 weeks. During each contact, the cotinine concentration was measured by NicAlert(TM) Saliva strip tests (NCTS). Descriptive statistics and Spearman's correlation (Spearman's rho) was used to examine the relationship between the variables at both 0.01 and 0.05 significant probability levels. This study indicated that GTS from dry tobacco production has the potential to be considered a common occupational disease. This study demonstrated the usefulness of salivary cotinine level measurements by NCTS. The levels were well correlated with farmers who were employed in the dry Thai tobacco production industry. Salivary cotinine levels were also significantly correlated with the prevalence of GTS in the group of tobacco farmers at any given time within a crop season. However, the production process of dry Thai traditional tobacco is different from that evaluated in our previous studies where GTS and salivary cotinine level were correlated in workers working in humid conditions. The long-term effects of such exposure

Single gas chromatography method with nitrogen phosphorus detector for urinary cotinine determination in passive and active smokers

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Lusiane Malafatti

2010-12-01

Full Text Available Nicotine is a major addictive compound in cigarettes and is rapidly and extensively metabolized to several metabolites in humans, including urinary cotinine, considered a biomarker due to its high concentration compared to other metabolites. The aim of this study was to develop a single method for determination of urinary cotinine, in active and passive smokers, by gas chromatography with a nitrogen phosphorus detector (GC-NPD. Urine (5.0 mL was extracted with 1.0 mL of sodium hydroxide 5 mol L-1, 5.0 mL of chloroform, and lidocaine used as the internal standard. Injection volume was 1 μL in GC-NPD. Limit of quantification was 10 ng mL-1. Linearity was evaluated in the ranges 10-1000 ng mL-1 and 500-6000 ng mL-1, with determination coefficients of 0.9986 and 0.9952, respectively. Intra- and inter-assay standard relative deviations were lower than 14.2 %, while inaccuracy (bias was less than +11.9%. The efficiency of extraction was greater than 88.5%. Ruggedness was verified, according to Youden's test. Means of cotinine concentrations observed were 2,980 ng mL-1 for active smokers and 132 ng mL-1, for passive smokers. The results revealed that satisfactory chromatographic separation between the analyte and interferents was obtained with a ZB-1 column. This method is reliable, precise, linear and presented ruggedness in the range evaluated. The results suggest that it can be applied in routine analysis for passive and active smokers, since it is able to quantify a wide range of cotinine concentrations in urine.A nicotina é uma substância presente no cigarro capaz de causar dependência, sendo biotransformada em vários metabólitos nos seres humanos, dentre eles a cotinina urinária, que é considerada um indicador biológico de exposição à nicotina, devido a suas altas concentrações, comparado a outras matrizes. Assim, o objetivo deste estudo foi desenvolver um único método para determinação de cotinina urinária, em amostras de

Gender differences in cadmium and cotinine levels in prepubertal children

DEFF Research Database (Denmark)

Fucic, A; Plavec, D; Casteleyn, L

2015-01-01

. In the total subsample group, the median level of Cd was 0.180µg/L (range 0.10-0.69µg/L), and for cotinine the median wet weight value was 1.50µg/L (range 0.80-39.91µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation...... and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old......), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1µg/L for Cd, and 0.8µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level...

Association between cotinine-verified smoking status and hypertension in 167,868 Korean adults.

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Kim, Byung Jin; Han, Ji Min; Kang, Jung Gyu; Kim, Bum Soo; Kang, Jin Ho

2017-10-01

Previous studies showed inconsistent results concerning the relationship between chronic smoking and blood pressure. Most of the studies involved self-reported smoking status. This study was performed to evaluate the association of urinary cotinine or self-reported smoking status with hypertension and blood pressure in Korean adults. Among individuals enrolled in the Kangbuk Samsung Health Study and Kangbuk Samsung Cohort Study, 167,868 participants (men, 55.7%; age, 37.5 ± 6.9 years) between 2011 and 2013 who had urinary cotinine measurements were included. Individuals with urinary cotinine levels ≥50 ng/mL were defined as cotinine-verified current smokers. The prevalence of hypertension and cotinine-verified current smokers in the overall population was 6.8% and 22.7%, respectively (10.0% in men and 2.8% in women for hypertension: 37.7% in men and 3.9% in women for cotinine-verified current smokers). In a multivariate regression analysis adjusted for age, sex, body mass index, waist circumference, alcohol drinking, vigorous exercise, and diabetes, cotinine-verified current smoking was associated with lower prevalence of hypertension compared with cotinine-verified never smoking (OR[95% CI], 0.79 [0.75, 0.84]). Log-transformed cotinine levels and unobserved smoking were negatively associated with hypertension, respectively (0.96 [0.96, 0.97] and 0.55 [0.39, 0.79]). In a multivariate linear regression analysis, the cotinine-verified current smoking was inversely associated with systolic and diastolic blood pressure (BP) (regression coefficient[95% CI], -1.23[-1.39, -1.07] for systolic BP and -0.71 [-0.84, -0.58] for diastolic BP). In subgroup analyses according to sex, the inverse associations between cotinine-verified current smoking and hypertension were observed only in men. This large observational study showed that cotinine-verified current smoking and unobserved smoking were inversely associated with hypertension in Korean adults, especially only in

Physical activity moderates the association between nicotine dependence and depression among U.S. smokers.

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Loprinzi, Paul D; Walker, Jerome F; Kane, Christy; Cardinal, Bradley J

2014-01-01

Research demonstrates that nicotine dependence and depression are associated and that physical activity is effective in reducing depression symptoms. However, our understanding of the potential beneficial effects of physical activity on depression in current smokers is more limited. The purpose of this study was to examine whether physical activity moderates the association between nicotine dependence and depression in U.S. smokers. Cross-sectional. National Health and Nutrition Examination Survey 2005-2006. Four hundred forty-one current adult smokers. Participants wore an accelerometer for at least 4 days and completed questionnaires to assess nicotine dependence and depression. Effect modification and statistical interaction models were used. Both models were significant. With regard to the statistical interaction model, and after controlling for age, gender, race/ethnicity, education, comorbidity index, homocysteine, cotinine, total cholesterol, sedentary behavior, and vitamins C, D, and E, objectively measured physical activity moderated the association between nicotine dependence and depression (interaction variable: odds ratio = 3.43; 95% confidence interval: 1.02-11.51; p = .04). In this national sample of current smokers, physical activity moderated the association between nicotine dependence and depression. These results suggest that those individuals with nicotine dependence and who are less physically active are more likely to be depressed than what would be expected on the basis of the individual effects of nicotine and physical inactivity separately.

Detection of tobacco-related biomarkers in urine samples by surface-enhanced Raman spectroscopy coupled with thin-layer chromatography.

Science.gov (United States)

Huang, Rongfu; Han, Sungyub; Li, Xiao Sheryl

2013-08-01

The nicotine metabolites, cotinine and trans-3'-hydroxycotinine (3HC) are considered as superior biomarkers for identifying tobacco exposure. More importantly, the ratio of 3HC to cotinine is a good indicator to phenotype individuals for cytochrome P450 2A6 activity and to individualize pharmacotherapy for tobacco addiction. In this paper, a simple, robust and novel method based on surface-enhanced Raman spectroscopy coupled with thin-layer chromatography (TLC) was developed to directly quantify the biomarkers in human urine samples. This is the first time surface-enhanced Raman spectroscopy (SERS) was used to detect cotinine and 3HC in urine samples. The linear dynamic range for the detection of cotinine is from 40 nM to 8 μM while that of 3HC is from 1 μM to 15 μM. The detection limits are 10 nM and 0.2 μM for cotinine and 3HC, respectively. The proposed method was further validated by quantifying the concentration of both cotinine and 3HC in smokers' urine samples. This TLC-SERS method allows the direct detection of cotinine in the urine samples of both active and passive smokers and the detection of 3HC in smokers.

Validity of Self-Reported Tobacco Smoke Exposure among Non-Smoking Adult Public Housing Residents.

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Shona C Fang

Full Text Available Tobacco smoke exposure (TSE in public multi-unit housing (MUH is of concern. However, the validity of self-reports for determining TSE among non-smoking residents in such housing is unclear.We analyzed data from 285 non-smoking public MUH residents living in non-smoking households in the Boston area. Participants were interviewed about personal TSE in various locations in the past 7 days and completed a diary of home TSE for 7 days. Self-reported TSE was validated against measurable saliva cotinine (lower limit of detection (LOD 0.02 ng/ml and airborne apartment nicotine (LOD 5 ng. Correlations, estimates of inter-measure agreement, and logistic regression assessed associations between self-reported TSE items and measurable cotinine and nicotine.Cotinine and nicotine levels were low in this sample (median = 0.026 ng/ml and 0.022 μg/m3, respectively. Prevalence of detectable personal TSE was 66.3% via self-report and 57.0% via measurable cotinine (median concentration among those with cotinine>LOD: 0.057 ng/ml, with poor agreement (kappa = 0.06; sensitivity = 68.9%; specificity = 37.1%. TSE in the home, car, and other peoples' homes was weakly associated with cotinine levels (Spearman correlations rs = 0.15-0.25, while TSE in public places was not associated with cotinine. Among those with airborne nicotine and daily diary data (n = 161, a smaller proportion had household TSE via self-report (41.6% compared with measurable airborne nicotine (53.4% (median concentration among those with nicotine>LOD: 0.04 μg/m3 (kappa = 0.09, sensitivity = 46.5%, specificity = 62.7%.Self-report alone was not adequate to identify individuals with TSE, as 31% with measurable cotinine and 53% with measurable nicotine did not report TSE. Self-report of TSE in private indoor spaces outside the home was most associated with measurable cotinine in this low-income non-smoking population.

Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

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Dani Smith

Full Text Available Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains.Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not.Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

Science.gov (United States)

Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P; Klein, Jonathan D; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

2015-01-01

Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study.

Science.gov (United States)

Shahab, Lion; Goniewicz, Maciej L; Blount, Benjamin C; Brown, Jamie; McNeill, Ann; Alwis, K Udeni; Feng, June; Wang, Lanqing; West, Robert

2017-03-21

Given the rapid increase in the popularity of e-cigarettes and the paucity of associated longitudinal health-related data, the need to assess the potential risks of long-term use is essential. To compare exposure to nicotine, tobacco-related carcinogens, and toxins among smokers of combustible cigarettes only, former smokers with long-term e-cigarette use only, former smokers with long-term nicotine replacement therapy (NRT) use only, long-term dual users of both combustible cigarettes and e-cigarettes, and long-term users of both combustible cigarettes and NRT. Cross-sectional study. United Kingdom. The following 5 groups were purposively recruited: combustible cigarette-only users, former smokers with long-term (≥6 months) e-cigarette-only or NRT-only use, and long-term dual combustible cigarette-e-cigarette or combustible cigarette-NRT users (n = 36 to 37 per group; total n = 181). Sociodemographic and smoking characteristics were assessed. Participants provided urine and saliva samples and were analyzed for biomarkers of nicotine, tobacco-specific N-nitrosamines (TSNAs), and volatile organic compounds (VOCs). After confounders were controlled for, no clear between-group differences in salivary or urinary biomarkers of nicotine intake were found. The e-cigarette-only and NRT-only users had significantly lower metabolite levels for TSNAs (including the carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]) and VOCs (including metabolites of the toxins acrolein; acrylamide; acrylonitrile; 1,3-butadiene; and ethylene oxide) than combustible cigarette-only, dual combustible cigarette-e-cigarette, or dual combustible cigarette-NRT users. The e-cigarette-only users had significantly lower NNAL levels than all other groups. Combustible cigarette-only, dual combustible cigarette-NRT, and dual combustible cigarette-e-cigarette users had largely similar levels of TSNA and VOC metabolites. Cross-sectional design with self-selected sample. Former

Self-reported smoking habits and serum cotinine levels in women with placental abruption.

Science.gov (United States)

Tikkanen, Minna; Surcel, Heljä-Marja; Bloigu, Aini; Nuutila, Mika; Ylikorkala, Olavi; Hiilesmaa, Vilho; Paavonen, Jorma

2010-12-01

smoking is an important risk factor for placental abruption with strong dose-dependency. Pregnant smokers often underreport tobacco use which can be objectively assessed by measuring serum cotinine levels. We examined the accuracy between self-reported smoking habits and early pregnancy serum cotinine levels in women with or without placental abruption. retrospective case-control study. university Hospital. a total of 175 women with placental abruption and 370 control women. serum samples collected during the first trimester were analyzed for serum cotinine levels. Cotinine concentration over 15 ng/ml was considered as the cutoff indicating active smoking. Smoking habits of the women and their partners were recorded at the same visit. placental abruption. of the cases of women with placental abruption, 27.4% reported smoking compared with 14.3% of the controls (p smoked daily correlated well with the cotinine levels (r = 0.68, p smoking habits correlate well with serum cotinine levels in Finland. Therefore, self-reported smoking can be considered as a risk marker for placental abruption.

Exposure to environmental tobacco smoke measured by cotinine 125I-radioimmunoassay

International Nuclear Information System (INIS)

Knight, G.J.; Palomaki, G.E.; Lea, D.H.; Haddow, J.E.

1989-01-01

We describe a polyclonal-antiserum-based 125 I-radioimmunoassay for cotinine that is suitable for measuring nonsmokers' passive exposure to tobacco smoke in the environment. The standard curve ranged from 0.25 to 12.0 micrograms/L, with an estimated lower limit of sensitivity of 0.2 microgram/L (95% B/Bo = 0.2 microgram/L; 50% B/Bo = 4.0 micrograms/L). The median within-assay CVs for patients' samples with cotinine values from 0.4 to 1.3, 1.4 to 2.4, 2.5 to 4.6, and 4.7 to 15.6 micrograms/L were 13.9%, 7.2%, 5.1%, and 5.7%, respectively. Between-assay CVs for two quality-control sera with average values of 1.53 and 3.68 micrograms/L were 14.3% and 7.8%, respectively. Analytical recoveries of cotinine from smokers' sera diluted in zero calibrant ranged from 91% to 116%. Cotinine values determined on 79 paired sera and urines from nonsmokers showed significant correlation with self-reported exposure to environmental tobacco smoke (r = 0.49, P less than 0.001 for sera; r = 0.57, P less than 0.001 for urine). The log of the values for serum and urine cotinine were also significantly correlated (r = 0.85, P less than 0.001). Evidently, polyclonal antiserum can be used to develop a cotinine assay for measuring exposure to environmental tobacco smoke that compares well with that described for monoclonal-based assays

Breast Milk and Hair Testing to Detect Illegal Drugs, Nicotine, and Caffeine in Donors to a Human Milk Bank.

Science.gov (United States)

Escuder-Vieco, Diana; Garcia-Algar, Óscar; Joya, Xavier; Marchei, Emilia; Pichini, Simona; Pacifici, Roberta; Pallás-Alonso, Carmen Rosa

2016-08-01

The use of illegal drugs and tobacco is an exclusion criteria for accepting a nursing mother as a milk donor. The detection window for human milk testing is typically a few hours. Hair testing has been considered the gold standard to assess chronic exposure to these toxic substances. The aim of this study was to determine the levels of illegal drugs, nicotine, and caffeine in breast milk and hair samples from donors to assess whether these substances were being used during the donation period and the months leading up to it. Thirty-six samples of hair and breast milk were obtained from 36 donors. The tests performed identified nicotine, caffeine, morphine, cocaine, cannabis, amphetamines, codeine, methadone, and other substances derived therefrom. No illegal drugs were found in any of the samples analyzed. Nicotine and cotinine were found in 33.3% (12/36) of all hair samples. Among these 12 samples, 10 had cotinine concentrations consistent with cutoff values for unexposed nonsmokers, 1 had concentrations consistent with cutoff values for passive smokers, and 1 had concentrations consistent with cutoff values for active smokers. Caffeine was found in 77.7% of the hair samples and in 50% of the donor milk samples. The correlation for caffeine between donor milk and hair samples was r = 0.288, P = .0881. Donors do not use illegal drugs during either the donation period or the months leading up to it. They are occasionally exposed to tobacco smoke and almost all of them consume caffeine. © The Author(s) 2016.

Variable effects of nicotine, anabasine, and their interactions on parasitized bumble bees

Science.gov (United States)

Thorburn, Lukas P.; Adler, Lynn S.; Irwin, Rebecca E.; Palmer-Young, Evan C.

2015-01-01

Secondary metabolites in floral nectar have been shown to reduce parasite load in two common bumble bee species. Previous studies on the effects of nectar secondary metabolites on parasitized bees have focused on single compounds in isolation; however, in nature, bees are simultaneously exposed to multiple compounds. We tested for interactions between the effects of two alkaloids found in the nectar of Nicotiana spp. plants, nicotine and anabasine, on parasite load and mortality in bumble bees ( Bombus impatiens) infected with the intestinal parasite Crithidia bombi. Adult worker bees inoculated with C. bombi were fed nicotine and anabasine diet treatments in a factorial design, resulting in four nectar treatment combinations:  2 ppm nicotine, 5 ppm anabasine, 2ppm nicotine and 5 ppm anabasine together, or a control alkaloid-free solution. We conducted the experiment twice: first, with bees incubated under variable environmental conditions (‘Variable’; temperatures varied from 10-35°C with ambient lighting); and second, under carefully controlled environmental conditions (‘Stable’; 27°C incubator, constant darkness). In ‘Variable’, each alkaloid alone significantly decreased parasite loads, but this effect was not realized with the alkaloids in combination, suggesting an antagonistic interaction. Nicotine but not anabasine significantly increased mortality, and the two compounds had no interactive effects on mortality. In ‘Stable’, nicotine significantly increased parasite loads, the opposite of its effect in ‘Variable’. While not significant, the relationship between anabasine and parasite loads was also positive. Interactive effects between the two alkaloids on parasite load were non-significant, but the pattern of antagonistic interaction was similar to that in the variable experiment. Neither alkaloid, nor their interaction, significantly affected mortality under controlled conditions. Our results do not indicate synergy between Nicotiana

Passive exposure to tobacco smoke: saliva cotinine concentrations in a representative population sample of non-smoking schoolchildren

Energy Technology Data Exchange (ETDEWEB)

Jarvis, M J; Russell, M A; Feyerabend, C; Eiser, J R; Morgan, M; Gammage, P; Gray, E M

1985-10-05

Saliva cotinine concentrations in 569 non-smoking schoolchildren were strongly related to the smoking habits of their parents. When neither parent smoked the mean concentration was 0.44 ng/ml, rising to 3.38 ng/ml when both parents were cigarette smokers. Mothers smoking had a stronger influence than did fathers (p less than 0.01). In addition, there was a small independent effect of number of siblings who smoked (p less than 0.01). The dose of nicotine received from fathers smoking was estimated as equivalent to the active smoking of 30 cigarettes a year, that from mothers smoking as equivalent to smoking 50 cigarettes a year, and that from both parents smoking as equivalent to smoking 80 cigarettes a year. This unsolicited burden may be prolonged throughout childhood and poses a definite risk to health.

The effects of taxes and bans on passive smoking

OpenAIRE

Jerome Adda; Francesca Cornaglia

2005-01-01

This paper evaluates the effect of excise taxes and bans on smoking in public places on the exposure to tobacco smoke of non-smokers. We use a novel way of quantifying passive smoking: we use data on cotinine concentration- a metabolite of nicotine- measured in a large population of non-smokers over time. Exploiting state and time variation across US states, we reach two important conclusions. First, excise taxes have a significant effect on passive smoking. Second, smoking bans have on avera...

The Effect of Taxes and Bans on Passive Smoking

OpenAIRE

Jérôme Adda; Francesca Cornaglia

2006-01-01

This paper evaluates the effect of excise taxes and bans on smoking in public places on the exposure to tobacco smoke of non-smokers. We use a novel way of quantifying passive smoking: we use data on cotinine concentration- a metabolite of nicotine- measured in a large population of non-smokers over time. Exploiting state and time variation across US states, we reach two important conclusions. First, excise taxes have a significant effect on passive smoking. Second, smoking bans have on avera...

Anti-smoking legislation and its effects on urinary cotinine and cadmium levels

Energy Technology Data Exchange (ETDEWEB)

Sánchez-Rodríguez, Jinny E., E-mail: jinnysanchez@isciii.es [Environmental Toxicology, Centro Nacional de Sanidad Ambiental (CNSA), Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km. 2, Majadahonda, 28220 Madrid (Spain); Bartolomé, Mónica, E-mail: mbj@isciii.es [Environmental Toxicology, Centro Nacional de Sanidad Ambiental (CNSA), Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km. 2, Majadahonda, 28220 Madrid (Spain); Cañas, Ana I, E-mail: acanas@isciii.es [Environmental Toxicology, Centro Nacional de Sanidad Ambiental (CNSA), Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km. 2, Majadahonda, 28220 Madrid (Spain); Huetos, Olga, E-mail: olgahh@isciii.es [Environmental Toxicology, Centro Nacional de Sanidad Ambiental (CNSA), Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km. 2, Majadahonda, 28220 Madrid (Spain); Navarro, Carmen, E-mail: carnavarro@isciii.es [Environmental Toxicology, Centro Nacional de Sanidad Ambiental (CNSA), Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km. 2, Majadahonda, 28220 Madrid (Spain); Rodríguez, A. Carolina, E-mail: acrodriguez@isciii.es [Environmental Toxicology, Centro Nacional de Sanidad Ambiental (CNSA), Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km. 2, Majadahonda, 28220 Madrid (Spain); Arribas, Misericordia, E-mail: marribas@isciii.es [Servicio de Prevención, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain); Esteban, Marta, E-mail: m.esteban@isciii.es [Environmental Toxicology, Centro Nacional de Sanidad Ambiental (CNSA), Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km. 2, Majadahonda, 28220 Madrid (Spain); López, Ana, E-mail: alopezh@isciii.es [Environmental Toxicology, Centro Nacional de Sanidad Ambiental (CNSA), Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km. 2, Majadahonda, 28220 Madrid (Spain); and others

2015-01-15

Anti-smoking legislation has been associated with an improvement in health indicators. Since the cadmium (Cd) body burden in the general population is markedly increased by smoke exposure, we analyzed the impact of the more restrictive legislation that came into force in Spain in 2011 by measuring Cd and cotinine in first morning urine samples from 83 adults in Madrid (Spain) before (2010) and after (2011) introduction of this law. Individual pair-wise comparisons showed a reduction of creatinine corrected Cotinine and Cd levels for non-active smokers, i. e. those which urinary cotinine levels are below 50 μg/L. After the application of the stricter law, cotinine levels in urine only decreased in non-active smokers who self-reported not to be exposed to second-hand smoke. The reduction in second hand smoke exposure was significantly higher in weekends (Friday to Sunday) than in working days (Monday to Thursday). The decrease in U-Cd was highly significant in non-active smokers and, in general, correlated with lower creatinine excretion. Therefore correction by creatinine could bias urinary Cd results, at least for cotinine levels higher than 500 μg/L. The biochemical/toxicological benefits detected herein support the stricter application of anti-smoking legislation and emphasize the need to raise the awareness of the population as regards exposure at home.

Anti-smoking legislation and its effects on urinary cotinine and cadmium levels

International Nuclear Information System (INIS)

Sánchez-Rodríguez, Jinny E.; Bartolomé, Mónica; Cañas, Ana I; Huetos, Olga; Navarro, Carmen; Rodríguez, A. Carolina; Arribas, Misericordia; Esteban, Marta; López, Ana

2015-01-01

Anti-smoking legislation has been associated with an improvement in health indicators. Since the cadmium (Cd) body burden in the general population is markedly increased by smoke exposure, we analyzed the impact of the more restrictive legislation that came into force in Spain in 2011 by measuring Cd and cotinine in first morning urine samples from 83 adults in Madrid (Spain) before (2010) and after (2011) introduction of this law. Individual pair-wise comparisons showed a reduction of creatinine corrected Cotinine and Cd levels for non-active smokers, i. e. those which urinary cotinine levels are below 50 μg/L. After the application of the stricter law, cotinine levels in urine only decreased in non-active smokers who self-reported not to be exposed to second-hand smoke. The reduction in second hand smoke exposure was significantly higher in weekends (Friday to Sunday) than in working days (Monday to Thursday). The decrease in U-Cd was highly significant in non-active smokers and, in general, correlated with lower creatinine excretion. Therefore correction by creatinine could bias urinary Cd results, at least for cotinine levels higher than 500 μg/L. The biochemical/toxicological benefits detected herein support the stricter application of anti-smoking legislation and emphasize the need to raise the awareness of the population as regards exposure at home

Current Status on Biochemistry and Molecular Biology of Microbial Degradation of Nicotine

Science.gov (United States)

Gurusamy, Raman; Natarajan, Sakthivel

2013-01-01

Bioremediation is one of the most promising methods to clean up polluted environments using highly efficient potent microbes. Microbes with specific enzymes and biochemical pathways are capable of degrading the tobacco alkaloids including highly toxic heterocyclic compound, nicotine. After the metabolic conversion, these nicotinophilic microbes use nicotine as the sole carbon, nitrogen, and energy source for their growth. Various nicotine degradation pathways such as demethylation pathway in fungi, pyridine pathway in Gram-positive bacteria, pyrrolidine pathway, and variant of pyridine and pyrrolidine pathways in Gram-negative bacteria have been reported. In this review, we discussed the nicotine-degrading pathways of microbes and their enzymes and biotechnological applications of nicotine intermediate metabolites. PMID:24470788

Elimination of cotinine from body fluids: implications for noninvasive measurement of tobacco smoke exposure.

Science.gov (United States)

Jarvis, M J; Russell, M A; Benowitz, N L; Feyerabend, C

1988-01-01

Cotinine elimination from plasma, saliva, and urine was studied over 11 days in five subjects (three nonsmokers and two occasional smokers). Half-lives for cotinine averaged 16-19 hours in the different body fluids (range 10 to 27 hours between subjects). There was no tendency for the half-life in saliva to be longer than in plasma or urine. We conclude that choice of body fluid for cotinine assay in smoking studies should depend on practical rather than pharmacokinetic considerations. PMID:3369603

Thirdhand smoke and exposure in California hotels: non-smoking rooms fail to protect non-smoking hotel guests from tobacco smoke exposure.

Science.gov (United States)

Matt, Georg E; Quintana, Penelope J E; Fortmann, Addie L; Zakarian, Joy M; Galaviz, Vanessa E; Chatfield, Dale A; Hoh, Eunha; Hovell, Melbourne F; Winston, Carl

2014-05-01

This study examined tobacco smoke pollution (also known as thirdhand smoke, THS) in hotels with and without complete smoking bans and investigated whether non-smoking guests staying overnight in these hotels were exposed to tobacco smoke pollutants. A stratified random sample of hotels with (n=10) and without (n=30) complete smoking bans was examined. Surfaces and air were analysed for tobacco smoke pollutants (ie, nicotine and 3-ethynylpyridine, 3EP). Non-smoking confederates who stayed overnight in guestrooms provided urine and finger wipe samples to determine exposure to nicotine and the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone as measured by their metabolites cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), respectively. Compared with hotels with complete smoking bans, surface nicotine and air 3EP were elevated in non-smoking and smoking rooms of hotels that allowed smoking. Air nicotine levels in smoking rooms were significantly higher than those in non-smoking rooms of hotels with and without complete smoking bans. Hallway surfaces outside of smoking rooms also showed higher levels of nicotine than those outside of non-smoking rooms. Non-smoking confederates staying in hotels without complete smoking bans showed higher levels of finger nicotine and urine cotinine than those staying in hotels with complete smoking bans. Confederates showed significant elevations in urinary NNAL after staying in the 10 most polluted rooms. Partial smoking bans in hotels do not protect non-smoking guests from exposure to tobacco smoke and tobacco-specific carcinogens. Non-smokers are advised to stay in hotels with complete smoking bans. Existing policies exempting hotels from complete smoking bans are ineffective.

Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

Energy Technology Data Exchange (ETDEWEB)

Lee, Sookwang; Busby, Andrea L.; Timchalk, Charles; Poet, Torka S.

2009-01-30

Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide which is metabolized by CYP450s to the neurotoxic metabolite, chlorpyrifos-oxon (CPF-oxon) and a non-toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP). The objective of this study was to quantify the effect of repeated in vivo nicotine exposures on CPF in vitro metabolism and marker substrate activities in rats. Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg/, for up to 10 days. Animals showed signs of cholinergic crisis after the initial nicotine doses, but exhibited adaptation after a couple days of treatment. Rats were sacrificed on selected days 4 or 24 hr after the last nicotine-treatment. While CYP450 reduced CO spectra were not different across the treatments, the single nicotine dose group showed a 2-fold increase in CYP2E1 marker substrate (p-nitrophenol) activity 24 hr after a single nicotine treatment compared to saline controls. Conversely, repeated nicotine treatments resulted in decreased EROD marker substrate activity 4 hr after the 7th day of treatment. CPF-oxon Vmax and Km did not show significant changes across the different nicotine treatment groups. The Vmax describing the metabolism of CPF to TCP was increased on all groups (days 1, 7, and 10) 24 hr after nicotine treatment but were unchanged 4 hr after nicotine treatment. Results of this in vitro study suggest that repeated nicotine exposure (i.e., from smoking) may result in altered metabolism of CPF. Future in vivo experiments based on these results will be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.

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

Energy Technology Data Exchange (ETDEWEB)

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

2005-05-01

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 mass 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.

Tobacco Product Use Patterns, and Nicotine and Tobacco-Specific Nitrosamine Exposure: NHANES 1999-2012.

Science.gov (United States)

Choi, Kelvin; Sabado, Melanie; El-Toukhy, Sherine; Vogtmann, Emily; Freedman, Neal D; Hatsukami, Dorothy

2017-10-01

Background: Few studies have examined differences in product consumption patterns and nicotine and tobacco-specific nitrosamines (TSNA) exposure between single versus dual- and poly-tobacco users. We applied the Tobacco Product Use Patterns (T-PUPs) model to fill this gap in the literature. Methods: Data from adults (age ≥18 years) who used any tobacco products during the 5 days prior to participating in the 1999-2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. Participants were classified into seven T-PUPs: (1) cigarettes only, (2) noncigarette combustibles only, (3) noncombustibles only, (4) dual noncigarette combustibles and noncombustibles, (5) dual cigarettes and noncombustibles, (6) dual cigarettes and noncigarette combustibles, and (7) poly-tobacco use. Weighted regression models were used to compare product consumption, serum cotinine, and urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (i.e., NNAL) levels between single-, dual-, and poly-tobacco T-PUPs. Results: Dual- and poly-tobacco T-PUPs were associated with lower product consumption compared with single-product T-PUPs only in some cases (e.g., dual cigarette and noncombustible users smoked cigarettes on 0.6 fewer days in the past 5 days compared with cigarette-only users; P product T-PUPs. Conclusions: Product consumption, and nicotine and TSNAs exposure of dual- and poly-tobacco product category users somewhat differ from those of single-product category users as defined by the T-TUPs model. Impact: Higher levels of cotinine and NNAL among dual- and poly-tobacco T-TUPs users compared with the single-product T-TUPs users may indicate health concerns. Cancer Epidemiol Biomarkers Prev; 26(10); 1525-30. ©2017 AACR . ©2017 American Association for Cancer Research.

Gender differences in cadmium and cotinine levels in prepubertal children

Energy Technology Data Exchange (ETDEWEB)

Fucic, A., E-mail: afucic@imi.hr [Institute for Medical Research and Occupational Health, Ksaverska c 2, 10000 Zagreb (Croatia); Plavec, D [Children Hospital Srebrnjak (Croatia); Casteleyn, L. [KU Leuven (Belgium); Aerts, D. [Federal Public Service Health, Food Chain Safety and Environment - DG Environment (Belgium); Biot, P. [DG Environment, Multilateral and Strategic Affairs (Belgium); Katsonouri, A. [State General Laboratory, Ministry of Health (Cyprus); Cerna, M. [Laboratoire National de Sante (Luxembourg); National Institute of Public Health (Czech Republic); Knudsen, L.E. [University of Copenhagen (Denmark); Castano, A. [Instituto de Salud Carlos III (Spain); Rudnai, P. [National Institute of Environmental Health (Hungary); Gutleb, A. [Centre de Recherche Public - Gabriel Lippmann (Luxembourg); Ligocka, D. [Nofer Institute of Occupational Medicine (Poland); Lupsa, I-R. [Environmental Health Center (Romania); Berglund, M. [Institute of Environmental Medicine, Karolinska Institutet (Sweden); Horvat, M. [Institute Josef Stefan (Slovenia); Halzlova, K. [Public Health Authority (Slovakia); State General Laboratory, Ministry of Health (Cyprus); Schoeters, G.; Koppen, G. [Flemish Institute for Technological Research (VITO), Environmental Risk and Health (Netherlands); Hadjipanayis, A. [Larnaca General Hospital, Ministry of Health, Republic of Cyprus (Cyprus); Krskova, A. [Laboratoire National de Sante (Luxembourg); National Institute of Public Health (Czech Republic); and others

2015-08-15

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age–sex groups: boys (6–8 years, 9–10 years and 11 years old), and girls (6–7 years, 8–9 years, 10–11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10–0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80–39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6–7 year old girls, 11 year old boys and 10–11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation. - Highlights: • In 216 children from 6 to 11 years old the median level of Cd was 0.18 µg/L. • The median level of cotinine was 1.50 µg/L. �

Jasmonate mediates salt-induced nicotine biosynthesis in tobacco (Nicotiana tabacum L.

Directory of Open Access Journals (Sweden)

Xiaodong Chen

2016-04-01

Full Text Available Jasmonate (JA, as an important signal, plays a key role in multiple processes of plant growth, development and stress response. Nicotine and related pyridine alkaloids in tobacco (Nicotiana tabacum L. are essential secondary metabolites. Whether environmental factors control nicotine biosynthesis and the underlying mechanism remains previously unreported. Here, we applied physiological and biochemical approaches to investigate how salt stress affects nicotine biosynthesis in tobacco. We found that salt stress induced the biosynthesis of JA, which subsequently triggered the activation of JA-responsive gene expression and, ultimately, nicotine synthesis. Bioinformatics analysis revealed the existence of many NtMYC2a-recognized G-box motifs in the promoter regions of NtLOX, NtAOS, NtAOC and NtOPR genes. Applying exogenous JA increased nicotine content, while suppressing JA biosynthesis reduced nicotine biosynthesis. Salt treatment could not efficiently induce nicotine biosynthesis in transgenic anti-COI1 tobacco plants. These results demonstrate that JA acts as the essential signal which triggers nicotine biosynthesis in tobacco after salt stress.

Decay kinetics of nicotine/NNK-DNA adducts in vivo studied by accelerator mass spectrometry

International Nuclear Information System (INIS)

Sun, H.F.; He, L.; Liu, Y.F.; Liu, K.X.; Lu, X.Y.; Wang, J.J.; Ma, H.J.; Li, K.

2000-01-01

The decay kinetics of nicotine-DNA adducts and NNK-DNA adducts in mice liver after single dosing was studied by accelerator mass spectrometry (AMS). The decay is characterized by a two-stage process. The half-lives of nicotine-DNA adducts are 1.3 d (4-24 h) and 7.0 d (1-21 d), while for NNK-DNA adducts are 0.7 d (4-24 h) and 18.0 d (1-21 d). The relatively faster decay of nicotine-DNA adducts suggests that the genotoxicity of nicotine is weaker than that of NNK. The in vitro study shows that the metabolization of nicotine is necessary for the final formation of nicotine-DNA adducts, and nicotine Δ1'(5') iminium ion is a probable metabolite species that binds to DNA molecule covalently

The relationship between self-reported tobacco exposure and cotinines in urine and blood for pregnant women.

Science.gov (United States)

Chiu, Hsien-Tsai; Isaac Wu, Hong-Dar; Kuo, Hsien-Wen

2008-11-15

To explore the relationship of self-reported exposure to tobacco smoke and the cotinine levels in the urine and blood over the follow-up period for pregnant women. Three hundred ninety-eight pregnant women undergoing prenatal care were interviewed in different trimesters at three hospitals in central Taiwan using a structured questionnaire. Based on their self-reported smoking experience, the participants were classified into three groups (25 smokers, 191 passive smokers, and 182 non-smokers) and were tracked in this study up to the time of delivery. Cotinine levels were tested for the maternal blood and urine at the end of each trimester and for the umbilical cord-blood of the newborns. All specimens were measured using a sensitive high-performance liquid chromatographic (HPLC) technique. In general, urinary cotinine levels were higher in subjects who smoked (including current- and ex-smokers) than those who never smoked. The pattern of distribution of cotinine levels among smoking/ETS exposure group in the urine sample was similar to that in the blood sample. The umbilical cord-blood cotinine levels was found to be highest in the active smoking group, followed by the ETS group exposed to ETS both at home and in the workplace. Over the course of the pregnancies, there was an increase in cotinine levels in urine and maternal blood for each of 3 exposure groups. Exposure to smoking by self-reported information in pregnant women has been found to be directly related to the levels of cotinine in the umbilical cord-blood of the fetus. Cotinine is a sensitive measure of ETS exposure, but if biochemical analysis is not available or convenient for a pregnant woman, then self-reported exposure to ETS can provide a good estimate if the information is gathered by a well-trained interviewer in a structured way.

Behavioral and Physiological Responses to Nicotine Patch Administration Among Nonsmokers Based on Acute and Chronic Secondhand Tobacco Smoke Exposure.

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Okoli, Chizimuzo; Kodet, Jonathan; Robertson, Heather

2016-01-01

Despite the large amount that is known about the physical health effects of secondhand tobacco smoke (SHS) exposure, little is known about the behavioral health effects. Nicotine, the principle psychoactive substance in SHS, elicits subjective mood and physiological responses in nonsmokers. However, no studies have examined the subjective mood or physiological responses to nicotine in nonsmokers while accounting for prior chronic or acute SHS exposure. A 7-mg nicotine patch was administered to 17 adult nonsmokers for 2 hr. Main outcome measures obtained at ½ hr, 1 hr, and 2 hr were subjective behavioral drug effects (based on eleven 10-cm Visual Analog Scales [VASs]) and the physiological measures of heart rate, blood pressure, and serum nicotine levels. Analysis of outcome data was based on participants' chronic (using hair nicotine) or acute (using saliva cotinine) SHS exposure. Greater chronic SHS exposure was negatively associated with pleasurable responses to nicotine administration ("drug feels good" score at 2-hr time point, Spearman's ρ = -.65, p < .004), whereas greater acute SHS exposure was associated with positive responses ("like feeling of drug" score at 2-hr time point, Spearman's ρ = .63, p < .01). There were no associations between chronic or acute exposure and physiological changes in response to nicotine administration. The findings of this study may be useful in providing preliminary empirical data for future explorations of the mechanism whereby SHS exposure can influence behavioral outcomes in nonsmokers. Such studies can inform future interventions to reduce the physical and behavioral health risks associated with SHS exposure. © The Author(s) 2015.

Influence of radioiodine therapy on ocular changes and their relation to urine cotinine level in patients with Graves' ophthalmopathy

International Nuclear Information System (INIS)

Czarnywojtek, A.; Czepczynski, R.; Budny, B.; Ruchata, M.; Zgorzalewicz-Stachowiak, M.; Florek, E.; Komar-Rychlicka, K.

2015-01-01

Full text of publication follows. Radioiodine therapy (RIT) is frequently used as the definitive treatment in patients with Graves' hyperthyroidism when remission is not achieved with anti-thyroid drugs (ATDs). In this observational study, we intended to examine whether the use of high doses of radioiodine (RAI) [22 mCi (814 MBq)] with prophylaxis of oral glucocorticoids (oGCS) does not exacerbate Graves ophthalmopathy (GO) in smokers and non-smokers, especially with regard to cotinine concentrations and ocular changes before and after RIT. Material and methods: The studied group consisted of 26 smokers, aged 28-61 years and 25 non-smoker patients, aged 21-54 years, respectively. The patients were qualified to RAI after one-year of ineffective ATDs treatment. Criterion for acceptance in the study were patients with mild GO with hyperthyroidism at diagnosis based on the severity (NOSPECS) and activity (CAS) scale. All the patients were subjected to RIT with oGCS prophylaxis and evaluated prospectively during a one-year follow-up. The ophthalmological examination was performed at various stages of RIT: initial pre-radioiodine administration, at the time of treatment 6, and 12 months after RAI. Urine cotinine measurement was employed to detect nicotine exposure, also in regard to smoking intensity. Results: TSHR-Abs concentration was higher in smokers (P < 0.05), rising from (22.9 ± 1.2) IU/l before therapy to (29.6 ± 5.3) IU/l at 2 months, (32.6 ± 8.6) IU/l at 6 months, and (28.9 ± 10.6) IU/l at 12 months after RIT. These observed changes were statistically different between groups at baseline (P < 0.05) and after one-year follow-up (P < 0.005). Mean urine cotinine were considerably higher in smokers comparing to non smokers in each point of. CAS values in the smoking group before RIT increased statistically from 2.8 ± 0.2 points at baseline to 4.3 ± 0.3 after 6 months, and 4.0 ± 0.5 (12 months), while in the non-smoking patients it was 1.4 ± 0.2, 2.8 �

Binding, uptake, and release of nicotine by human gingival fibroblasts

International Nuclear Information System (INIS)

Hanes, P.J.; Schuster, G.S.; Lubas, S.

1991-01-01

Previous studies of the effects of nicotine on fibroblasts have reported an altered morphology and attachment of fibroblasts to substrates and disturbances in protein synthesis and secretion. This altered functional and attachment response may be associated with changes in the cell membrane resulting from binding of the nicotine, or to disturbances in cell metabolism as a result of high intracellular levels of nicotine. The purpose of the present study, therefore, was to (1) determine whether gingival fibroblasts bound nicotine and if any binding observed was specific or non-specific in nature; (2) determine whether gingival fibroblasts internalized nicotine, and if so, at what rate; (3) determine whether gingival fibroblasts also released nicotine back into the extracellular environment; and (4) if gingival fibroblasts release nicotine intact or as a metabolite. Cultures of gingival fibroblasts were prepared from gingival connective tissue biopsies. Binding was evaluated at 4 degree C using a mixture of 3 H-nicotine and unlabeled nicotine. Specific binding was calculated as the difference between 3 H-nicotine bound in the presence and absence of unlabeled nicotine. The cells bound 1.44 (+/- 0.42) pmols/10(6) cells in the presence of unlabeled nicotine and 1.66 (+/- 0.55) pmols/10(6) cells in the absence of unlabeled nicotine. The difference was not significant. Uptake of nicotine was measured at 37 degree C after treating cells with 3 H-nicotine for time periods up to 4 hours. Uptake in pmols/10(6) cells was 4.90 (+/- 0.34) at 15 minutes, 8.30 (+/- 0.75) at 30 minutes, 12.28 (+/- 2.62) at 1 hour and 26.31 (+/- 1.15) at 4 hours

Hedonic Predictors of Tobacco Dependence: A Puff Guide to Smoking Cessation

Science.gov (United States)

2015-04-07

process may not always be the case. While Perkins et al. (31) showed the potential for a connection between puff volume, considered reinforcement...effect can be attributed to the effects of "acute tolerance" (31 ). Nicotine is thought to acutely desensitize nicotinic receptors ("acute tolerance...company that performs biological assays) for the cotinine assay. Salivary cotinine levels were measured through an enzyme immunoassay conducted by

Modulation of social deficits and repetitive behaviors in a mouse model of autism: the role of the nicotinic cholinergic system.

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Wang, Li; Almeida, Luis E F; Spornick, Nicholas A; Kenyon, Nicholas; Kamimura, Sayuri; Khaibullina, Alfia; Nouraie, Mehdi; Quezado, Zenaide M N

2015-12-01

Accumulating evidence implicates the nicotinic cholinergic system in autism spectrum disorder (ASD) pathobiology. Neuropathologic studies suggest that nicotinic acetylcholine (ACh) receptor (nAChR) subtypes are altered in brain of autistic individuals. In addition, strategies that increase ACh, the neurotransmitter for nicotinic and muscarinic receptors, appear to improve cognitive deficits in neuropsychiatric disorders and ASD. The aim of this study is to examine the role of the nicotinic cholinergic system on social and repetitive behavior abnormalities and exploratory physical activity in a well-studied model of autism, the BTBR T(+) Itpr3 (tf) /J (BTBR) mouse. Using a protocol known to up-regulate expression of brain nAChR subtypes, we measured behavior outcomes before and after BTBR and C57BL/6J (B6) mice were treated (4 weeks) with vehicle or nicotine (50, 100, 200, or 400 μg/ml). Increasing nicotine doses were associated with decreases in water intake, increases in plasma cotinine levels, and at the higher dose (400 μg/ml) with weight loss in BTBR mice. At lower (50, 100 μg/ml) but not higher (200, 400 μg/ml) doses, nicotine increased social interactions in BTBR and B6 mice and at higher, but not lower doses, it decreased repetitive behavior in BTBR. In the open-field test, nicotine at 200 and 400 μg/ml, but not 100 μg/ml compared with vehicle, decreased overall physical activity in BTBR mice. These findings support the hypotheses that the nicotinic cholinergic system modulates social and repetitive behaviors and may be a therapeutic target to treat behavior deficits in ASD. Further, the BTBR mouse may be valuable for investigations of the role of nAChRs in social deficits and repetitive behavior.

Variable effects of nicotine, anabasine, and their interactions on parasitized bumble bees [version 2; referees: 2 approved

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Lukas P. Thorburn

2015-12-01

Full Text Available Secondary metabolites in floral nectar have been shown to reduce parasite load in two common bumble bee species. Previous studies on the effects of nectar secondary metabolites on parasitized bees have focused on single compounds in isolation; however, in nature, bees are simultaneously exposed to multiple compounds. We tested for interactions between the effects of two alkaloids found in the nectar of Nicotiana spp. plants, nicotine and anabasine, on parasite load and mortality in bumble bees (Bombus impatiens infected with the intestinal parasite Crithidia bombi. Adult worker bees inoculated with C. bombi were fed nicotine and anabasine diet treatments in a factorial design, resulting in four nectar treatment combinations:  2 ppm nicotine, 5 ppm anabasine, 2ppm nicotine and 5 ppm anabasine together, or a control alkaloid-free solution. We conducted the experiment twice: first, with bees incubated under variable environmental conditions (‘Variable’; temperatures varied from 10-35°C with ambient lighting; and second, under carefully controlled environmental conditions (‘Stable’; 27°C incubator, constant darkness. In ‘Variable’, each alkaloid alone significantly decreased parasite loads, but this effect was not realized with the alkaloids in combination, suggesting an antagonistic interaction. Nicotine but not anabasine significantly increased mortality, and the two compounds had no interactive effects on mortality. In ‘Stable’, nicotine significantly increased parasite loads, the opposite of its effect in ‘Variable’. While not significant, the relationship between anabasine and parasite loads was also positive. Interactive effects between the two alkaloids on parasite load were non-significant, but the pattern of antagonistic interaction was similar to that in the variable experiment. Neither alkaloid, nor their interaction, significantly affected mortality under controlled conditions. Our results do not indicate synergy

Variation of serum and urine cotinine in passive and active smokers and applicability in preconceptional smoking cessation counseling

International Nuclear Information System (INIS)

Weerd, Sabina de; Thomas, Chris M.G.; Kuster, Josien E.T.G.; Cikot, Rolf J.L.M.; Steegers, Eric A.P.

2002-01-01

This study assessed the applicability of serum and urine cotinine as a biochemical marker of self-reported smoking habits for use in a preconception smoking cessation program. The variation of serum and urine cotinine over the course of the day was investigated in a sample of 21 smokers and 8 passive smokers who reported their smoking habits and exposure to smoke daily in a questionnaire for 10 consecutive days. Blood and urine samples were collected on two sampling days, 1 week apart. Both serum and urine cotinine assay could distinguish between passive and active smokers, but not between higher categories of smokers (1019 and ≥20 cigarettes per ay) due to significant intersubject overlap. In serum, no significant differences were found between morning and afternoon cotinine concentrations in either day, in contrast to urine cotinine (with lower excretions observed n the morning). An overall coefficient of variation of 22- was observed for both specimens in smokers. Because serum cotinine is subject to lower variability over the course of the day, it is more practical for use in a clinical setting where appointments are scheduled throughout the day in order o confirm smoking status

Measuring tobacco smoke exposure: quantifying nicotine/cotinine concentration in biological samples by colorimetry, chromatography and immunoassay methods.

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Dhar, Preeti

2004-04-01

Procedures to assess tobacco smoke exposure are reviewed and biomarkers used for determining the smoking status of an individual are compared. Methods used to extract these biomarkers from saliva, urine, and blood and the advantages and disadvantages of the assays are discussed. Finally, the procedures used to measure the levels of cortisol, a stress hormone speculated to be linked to nicotine metabolism, are discussed.

Characterization of urinary cotinine in non-smoking residents in smoke-free homes in the Korean National Environmental Health Survey (KoNEHS

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Jeonghoon Kim

2016-07-01

Full Text Available Abstract Background The objectives of this study were to determine urinary cotinine concentrations in non-smoking residents of smoke-free homes and to establish the relationship of urinary cotinine with housing type and other socio-demographic and secondhand smoke (SHS exposure factors. Methods We used data from the Korean National Environmental Health Survey I (2009–2011. The study included 814 non-smoking adult residents living in apartments, attached, and detached housing. Residents who lived with smokers were excluded. Urinary cotinine concentration was used as a biomarker for SHS exposure. The factors associated with urinary cotinine levels in non-smoking residents were determined using multivariate regression analysis. Results Urinary cotinine was detected in 88 % of the 814 non-smoking residents of smoke-free homes. The urinary cotinine concentrations of residents living in attached [1.18 ng/mg creatinine (Cr] and detached housing (1.23 ng/mg Cr were significantly higher than those of residents who lived in apartments (0.69 ng/mg Cr. Urinary cotinine concentrations were significantly higher in residents who were men, those with a household income ≤1000 USD/month, those who were former smokers with >1 year and ≤1 year of not smoking, and those who experienced SHS odor every day. In the multivariate regression analysis, housing type, sex, former smoking status, and frequency of experiencing SHS odor were associated with urinary cotinine concentrations (R 2 = 0.14. Conclusions The majority of non-smoking residents of smoke-free homes had detectable urinary cotinine. Housing type, sex, former smoking status, and frequency of experiencing SHS odor were predictors for urinary cotinine concentrations in the study participants.

Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice.

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Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Mendoza, Cristhian; Perez-Urrutia, Nelson; Echeverria, Florencia; Iarkov, Alexandre; Barreto, George E; Echeverria, Valentina

2018-02-27

Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice. Since calcineurin A has been involved in facilitating fear extinction in rodents, we also investigated changes of calcineurin in the hippocampus, a region key on contextual fear extinction. Short-term treatment with cotinine formulations was superior to krill oil and oral sertraline in reducing depressive-like behavior and fear consolidation and enhancing contextual fear memory extinction in mice. IN krill oil slowed the extinction of fear. IN cotinine preparations increased the levels of calcineurin A in the hippocampus of conditioned mice. In the light of the results, the future investigation of the use of IN cotinine preparations for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) in PTSD is discussed.

Validation of self-reported smoking status by measuring serum cotinine levels: an Indian perspective.

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Jeemon, P; Agarwal, S; Ramakrishnan, L; Gupta, R; Snehi, U; Chaturvedi, V; Reddy, K S; Prabhakaran, D

2010-01-01

Serum cotinine levels are a reliable marker of tobacco use. Few studies have validated questionnaires assessing smoking and exposure to environmental tobacco smoke (ETS) against serum levels. We undertook such a study in industrial workers in India. We chose 426 individuals by stratified random sampling from a database of 3397 individuals surveyed at New Delhi for the cardiovascular disease surveillance programme in a large industrial setting. Questionnaires assessing details of smoking practices and duration of exposure to ETS (if any) were administered. Cotinine levels were measured in the blood samples of these individuals. The study population comprised 142 nonsmokers not exposed to ETS, 142 non-smokers exposed to ETS and 142 active smokers. Cotinine levels among nonsmokers not exposed to ETS were non-detectable; and for non-smokers exposed to ETS and active smokers, the median (interquartile range) levels were non-detectable (non-detectable to 46.1 ng/ml) and 336 ng/ml (204-500 ng/ml), respectively. The best combined sensitivity (91%) and specificity (87.2%) yielded a cotinine cut-off level of 40.35 ng/ml to differentiate active smokers from non-smokers not exposed to ETS and those exposed to ETS (area under the curve 0.902). The cut-off cotinine level was estimated at 10.95 ng/ml using a similar analysis (sensitivity 43%, specificity 82%; area under the curve 0.64) to distinguish non-smokers not exposed to ETS from those exposed to ETS. The misclassification rate was estimated at 19% and 57.1% among self-reported non-smokers not exposed to ETS and those exposed to ETS, respectively. Obtaining a history of tobacco use is an accurate method of detecting smokers in epidemiological studies whereas serum cotinine levels accurately differentiate smokers from non-smokers. However, a brief questionnaire assessing passive exposure to smoke has poor sensitivity in distinguishing non-smokers exposed to ETS from those not exposed to ETS.

Elevada concentración de metabolitos de cotinina en hijos de padres fumadores High levels of cotinine metabolite in smoker's parents children

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Eduardo Lazcano-Ponce

2007-01-01

ños, no sólo de padres fumadores sino también de padres no fumadores. Esto pone de relevancia que la exposición al HTSM no es sólo un problema de salud pública que se presenta en hogares de padres fumadores, sino que la exposición en niños mexicanos es frecuente en diversos lugares públicos. Es necesario implementar estudios adicionales en México para evaluar el impacto de intervenciones que garanticen hogares y espacios libres de humo de tabaco.INTRODUCTION: Children and adult exposure to SecondHand Smoke (SHS may occur in government offices, work and public places as well as in vehicles. Nevertheless, SHS is particularly important at home. High exposure levels in children may be the main reason to prevent parents and other family members from smoking at home. This study aims at establishing SHS levels by measuring biomakers in serum in pairs of parents and their younger than five years old children in Mexico, included in the 2000 National Health Survey. MATERIAL AND METHODS: Seventy-six parents-children pairs were taken from households with non smokers adults, as well as 83 pairs with adult smokers at home. Selection was limited to the adult population in households with children under five years old. Serum samples were analyzed through liquid chromatographic. Correlation exposure models between parents-children pairs were built and stratified according to parents’ background concerning smoking. RESULTS: In the smokers group, people with more than 15ng/mL of cotinine metabolites in serum showed prevalence of 100%. Minimum quantification was 18.50 and maximum 221.5ng/mL. In adults, cotinine metabolite levels in serun were 50 times higher in smokers (107.4ng/mL, than in non smokers (1.99 ng/mL. Concerning 3-hydroxycotinine, something similar was observed (0.60 in non smokers vs. 33.50 ng/mL in smokers. A significant difference three times higher in cotinine levels (0.10 vs. 0.60ng/mL and 3-hydroxycotinine (0.06 vs. 0.19ng/mL was found in those children with, at

Atomoxetine treatment for nicotine withdrawal: a pilot double-blind, placebo-controlled, fixed-dose study in adult smokers

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Silverstone Peter H

2012-03-01

Full Text Available Abstract Background Many effective treatments for nicotine addiction inhibit noradrenaline reuptake. Three recent studies have suggested that another noradrenaline reuptake inhibitor, atomoxetine, may reduce smoking behaviors. Methods The present double-blind, placebo-controlled, fixed-dose study was carried out over 21 days during which administration of 40 mg atomoxetine was compared to placebo in 17 individuals. Of these, nine were randomized to atomoxetine and eight to placebo. Baseline and weekly measurements were made using the Cigarette Dependence Scale (CDS, Cigarette Withdrawal Scale (CWS, Questionnaire of Smoking Urges (QSU, reported number of cigarettes smoked, and salivary cotinine levels. Results The study results showed that all those on placebo completed the study. In marked contrast, of the nine individuals who started on atomoxetine, five dropped out due to side effects. In a completer analysis there were statistically significant differences at 14 and 21 days in several measures between the atomoxetine and placebo groups, including CDS, CWS, QSU, number of cigarettes smoked (decreasing to less than two per day in the treatment group who completed the study, and a trend towards lower mean salivary cotinine levels. However, these differences were not seen in a last observation carried forward (LOCF analysis. Conclusions In summary, this is the first study to examine the use of atomoxetine in non-psychiatric adult smokers for a period of more than 7 days, and the findings suggest that atomoxetine might be a useful treatment for nicotine addiction. However, the dose used in the current study was too high to be tolerated by many adults, and a dose-finding study is required to determine the most appropriate dose for future studies of this potential treatment for smoking cessation.

Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

Energy Technology Data Exchange (ETDEWEB)

Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

2010-03-30

Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF

Are students exposed to tobacco smoke in German schools?

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Heinrich, Joachim

2005-12-01

Full Text Available The aim of this study was to investigate to which extent 6th grade school children are exposed to tobacco smoke by others. As biomarker for the exposure to tobacco smoke nicotine and cotinine were measured in the urine. Our study population consisted of 771 schoolchildren aged 11-14 years who according to a questionnaire did not smoke. In addition we analysed the data of 459 school children who were not exposed to tobacco smoke at home. The nicotine and cotinine concentrations in the spontaneous urine sample were determined by HPLC methods.On average in about 20% of all non-smoking children, who were not exposed to tobacco smoke at home, biomarker (nicotine or cotinine were detected in the urine. The percentage of the detected biomarker values (nicotine and/or cotinine in the urine of the school children varied between 0% and 50% between schools. In addition we determined the proportion of smoking classmates per school. No positive association was found between the detected biomarker values of the non-smoking school children not exposed to tobacco smoke at home and the proportion of smokers per school. The concentration of biomarker depending on the time of day the urine samples were collected showed higher nicotine and cotinine values when the urine sample was collected between 10 and 12 o'clock in the morning compared to urine samples collected between 7 and 10 a.m.In spite of the limitations our study provides some evidence that children are exposed involuntarily to tobacco smoke by others at school. That is why our results support the requirement of a general legal ban on smoking for teachers, the school staff and students.

The Danish contribution to the European DEMOCOPHES project: A description of cadmium, cotinine and mercury levels in Danish mother-child pairs and the perspectives of supplementary sampling and measurements.

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Mørck, Thit A; Nielsen, Flemming; Nielsen, Jeanette K S; Jensen, Janne F; Hansen, Pernille W; Hansen, Anne K; Christoffersen, Lea N; Siersma, Volkert D; Larsen, Ida H; Hohlmann, Linette K; Skaanild, Mette T; Frederiksen, Hanne; Biot, Pierre; Casteleyn, Ludwine; Kolossa-Gehring, Marike; Schwedler, Gerda; Castaño, Argelia; Angerer, Jürgen; Koch, Holger M; Esteban, Marta; Schoeters, Greet; Den Hond, Elly; Exley, Karen; Sepai, Ovnair; Bloemen, Louis; Joas, Reinhard; Joas, Anke; Fiddicke, Ulrike; Lopez, Ana; Cañas, Ana; Aerts, Dominique; Knudsen, Lisbeth E

2015-08-01

Human biomonitoring (HBM) is an important tool, increasingly used for measuring true levels of the body burdens of environmental chemicals in the general population. In Europe, a harmonized HBM program was needed to open the possibility to compare levels across borders. To explore the prospect of a harmonized European HBM project, DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) was completed in 17 European countries. The basic measurements performed in all implemented countries of DEMOCOPHES included cadmium, cotinine and phthalate metabolites in urine and mercury in hair. In the Danish participants, significant correlations between mothers and children for mercury in hair and cotinine in urine were found. Mercury in hair was further significantly associated with intake of fish and area of residence. Cadmium was positively associated with BMI in mothers and an association between cadmium and cotinine was also found. As expected high cotinine levels were found in smoking mothers. For both mercury and cadmium significantly higher concentrations were found in the mothers compared to their children. In Denmark, the DEMOCOPHES project was co-financed by the Danish ministries of health, environment and food safety. The co-financing ministries agreed to finance a number of supplementary measurements of substances of current toxicological, public and regulatory interest. This also included blood sampling from the participants. The collected urine and blood samples were analyzed for a range of other persistent and non-persistent environmental chemicals as well as two biomarkers of effect. The variety of supplementary measurements gives the researchers further information on the exposure status of the participants and creates a basis for valuable knowledge on the pattern of exposure to various chemicals. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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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.

Waterpipe tobacco products: nicotine labelling versus nicotine delivery.

Science.gov (United States)

Vansickel, Andrea R; Shihadeh, Alan; Eissenberg, Thomas

2012-05-01

Waterpipe tobacco package labelling typically indicates "0.0% tar" and "0.05% or 0.5% nicotine". To determine the extent to which nicotine labeling is related to nicotine delivery. 110 waterpipe smokers engaged in a 45-minute waterpipe smoking session. Puff topography and plasma nicotine were measured. Three waterpipe tobacco brands were used: Nakhla (0.5% nicotine), Starbuzz (0.05% nicotine), and Al Fakher (0.05% nicotine). Data were analyzed by one-way ANOVA. Topography did not differ across brands. Peak plasma nicotine varied significantly across brands. Al Fakher had the highest nicotine delivery (11.4 ng/ml) followed by Nakhla (9.8 ng/ml) and Starbuzz (5.8 ng/ml). Nicotine labelling on waterpipe tobacco products does not reflect delivery; smoking a brand with a "0.05% nicotine" label led to greater plasma nicotine levels than smoking a brand with a "0.5% nicotine" label. Waterpipe tobacco products should be labelled in a manner that does not mislead consumers.

Estimation of Cutoff Values of Cotinine in Urine and Saliva for Pregnant Women in Poland

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Joanna Stragierowicz

2013-01-01

Full Text Available Setting appropriate cutoff values and the use of a highly sensitive analytical method allow for correct classification of the smoking status. Urine-saliva pairs samples of pregnant women in the second and third trimester, and saliva only in the first trimester were collected. Offline SPE and LC-ESI-MS/MS method was developed in the broad concentration range (saliva 0.4–1000 ng/mL, urine 0.8–4000 ng/mL. The mean recoveries were 3.7±7.6% for urine and 99.1±2.6% for saliva. LOD for saliva was 0.12 ng/mL and for urine 0.05 ng/mL; LOQ was 0.4 ng/mL and 0.8 ng/mL, respectively. Intraday and interday precision equaled, respectively, 1.2% and 3.4% for urine, and 2.3% and 6.4% for saliva. There was a strong correlation between salivary cotinine and the uncorrected cotinine concentration in urine in the second and third trimesters of pregnancy. The cutoff values were established for saliva 12.9 ng/mL and urine 42.3 ng/mL or 53.1 μg/g creatinine with the ROC curve analysis. The developed analytical method was successfully applied to quantify cotinine, and a significant correlation between the urinary and salivary cotinine levels was found. The presented cut-off values for salivary and urinary cotinine ensure a categorization of the smoking status among pregnant women that is more accurate than self-reporting.

A rapid assay for the simultaneous determination of nicotine, cocaine and metabolites in meconium using disposable pipette extraction and gas chromatography-mass spectrometry (GC-MS).

Science.gov (United States)

Mozaner Bordin, Dayanne C; Alves, Marcela N R; Cabrices, Oscar G; de Campos, Eduardo G; De Martinis, Bruno Spinosa

2014-01-01

Drug abuse by pregnant women is considered a serious public health problem worldwide. Meconium is the first excretion in newborns and has been used as an alternative matrix to evaluate in utero drug exposure. Solid phase extraction (SPE) is widely employed to prepare and clean up samples in the field of forensic analysis. Most SPE products require large volumes of solvent, which culminates in longer sample processing times and increased cost per sample. Disposable pipette extraction (DPX) tips have been used as an alternative to traditional SPE cartridges. They combine efficient and rapid extraction with reduced solvent consumption. The purpose of this study was to develop and validate a method to determine nicotine, cotinine, cocaine, benzoylecgonine, cocaethylene and methyl ester anhydroecgonine in meconium using DPX and gas chromatography-mass spectrometry (GC-MS). Validation results indicated that extraction efficiency ranged 50-98%, accuracy 92-106%, intra-assay precision 4-12% and inter-assay precision 6-12%. Linear calibration curves resulted in R(2) values >0.99, limits of detection ranged from 2.5 to 15 ng/g and the limit of quantitation from 10 to 20 ng/g. The DPX-GC-MS method was shown to selectively analyze trace concentrations of drugs in meconium samples. Finally, the developed and validated method was applied to 50 meconium samples.

Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

2013-01-15

Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

Accuracy of cotinine serum test to detect the smoking habit and its association with periodontal disease in a multicenter study.

Science.gov (United States)

Duque, A; Martínez, P-J; Giraldo, A; Gualtero, D-F; Ardila, C-M; Contreras, A; Duarte, S; Lafaurie, G-I

2017-07-01

The validity of the surveys on self-reported smoking status is often questioned because smokers underestimate cigarette use and deny the habit. It has been suggested that self-report should be accompanied by cotinine test. This report evaluates the usefulness of serum cotinine test to assess the association between smoking and periodontal status in a study with a large sample population to be used in studies with other serum markers in epidemiologic and periodontal medicine researches. 578 patients who were part of a multicenter study on blood biomarkers were evaluated about smoking and its relation to periodontal disease. Severity of periodontal disease was determinate using clinical attachment loss (CAL). Smoking was assessed by a questionnaire and a blood sample drawn for serum cotinine determination. The optimal cut-off point for serum cotinine was 10 ng/ml. Serum cotinine showed greater association with severity of CAL than self-report for mild-moderate CAL [OR 2.03 (CI95% 1.16-3.53) vs. OR 1.08 (CI95% 0.62-1.87) ] advanced periodontitis [OR 2.36 (CI95% 1.30- 4.31) vs. OR 2.06 (CI95% 0.97-4.38) ] and extension of CAL > 3 mm [ OR 1.78 (CI95% 1.16-1.71) vs. 1.37 (CI95% 0.89-2.11)]. When the two tests were evaluated together were not shown to be better than serum cotinine test. Self-reported smoking and serum cotinine test ≥ 10ng/ml are accurate ,complementary and more reliable methods to assess the patient's smoking status and could be used in studies evaluating serum samples in large population and multicenter studies. The serum cotinine level is more reliable to make associations with the patient's periodontal status than self-report questionnaire and could be used in multicenter and periodontal medicine studies.

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

Science.gov (United States)

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.

Effects of nicotine on the digestive performance of nectar-feeding birds reflect their relative tolerance to this alkaloid.

Science.gov (United States)

Lerch-Henning, S; Nicolson, S W

2015-12-01

The paradox of secondary metabolites, toxic defence compounds produced by plants, in nectar and fruits is well known. Deterrence of feeding by nectarivorous and frugivorous birds is better understood than the effect of these chemicals on the digestive performance of birds. Digestive parameters such as transit time and sugar assimilation are important in assessing nutrient utilization and deterrence may be related to post-ingestive effects involving these parameters. Nectar and many fruits contain mainly sugars and water, and avian consumers compensate for low sugar content in their diet by increasing food intake: this may also increase their intake of secondary metabolites. We investigated how the alkaloid nicotine, naturally present in nectar of Nicotiana species, influences compensatory feeding and digestive performance of nectar-feeding birds. High nicotine concentration negatively affected compensatory feeding and apparent assimilation efficiency of white-bellied sunbirds Cinnyris talatala and Cape white-eyes Zosterops virens; but nicotine slowed gut transit time only in the latter species. In contrast, food intake and digestive performance of dark-capped bulbuls Pycnonotus tricolor was unaffected by nicotine up to a concentration of 50μM. Bulbuls are primarily frugivorous; hence, they are more exposed to secondary metabolites than sunbirds and possibly white-eyes. Because their diet is richer in toxins, frugivorous birds may have evolved more efficient detoxification strategies than those of specialist nectar-feeding birds. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel pathway for nicotine degradation by Aspergillus oryzae 112822 isolated from tobacco leaves.

Science.gov (United States)

Meng, Xiang Jing; Lu, Li Li; Gu, Guo Feng; Xiao, Min

2010-09-01

An efficient nicotine-degrading fungus was isolated from tobacco leaves and identified as Aspergillus oryzae 112822 based on morphological characteristics and sequence analysis of 18S rDNA, 5.8S rDNA and the internal transcribed spacer (5.8S-ITS region). When the strain was cultured in a medium with tobacco leaf extract for 40 h, the maximum amount of cell growth was 3.6 g l(-1) and nicotine degradation was 2.19 g l(-1). The intermediates of nicotine degradation by resting cells were isolated by preparative TLC or semi-preparative HPLC, and identified by TLC, MS, NMR, Fourier-transform (FT)-IR and GC-MS analysis. The pathway for nicotine degradation in A. oryzae 112822 was proposed to be from nicotine to 2,3-dihydroxypyridine through the intermediates nornicotine, myosmine, N-methylnicotinamide and 2-hydroxy-N-methylnicotinamide. The ring of 2,3-dihydroxypyridine was opened between the 2- and 3-hydroxy positions to yield succinic acid. N-methylnicotinamide and 2,3-dihydroxypyridine were satisfactorily verified as metabolites of nicotine degradation. This is the first elucidation of a pathway for nicotine degradation in fungi. Copyright 2010 Elsevier Masson SAS. All rights reserved.

The Danish contribution to the European DEMOCOPHES project: A description of cadmium, cotinine and mercury levels in Danish mother-child pairs and the perspectives of supplementary sampling and measurements

Energy Technology Data Exchange (ETDEWEB)

Mørck, Thit A. [Department of Public Health, University of Copenhagen, Copenhagen (Denmark); Nielsen, Flemming [Department of Public Health, University of Southern Denmark, Odense (Denmark); Nielsen, Jeanette K.S.; Jensen, Janne F.; Hansen, Pernille W.; Hansen, Anne K.; Christoffersen, Lea N. [Department of Public Health, University of Copenhagen, Copenhagen (Denmark); Siersma, Volkert D. [The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen (Denmark); Larsen, Ida H.; Hohlmann, Linette K. [Department of Public Health, University of Copenhagen, Copenhagen (Denmark); Skaanild, Mette T. [Danish Environmental Protection Agency (Denmark); Frederiksen, Hanne [Department of Growth and Reproduction, University Hospital, Copenhagen (Denmark); Biot, Pierre [Federal Public Service Health, Food Chain Safety and Environment, Brussels (Belgium); Casteleyn, Ludwine [University of Leuven, Leuven (Belgium); Kolossa-Gehring, Marike; Schwedler, Gerda [Federal Environment Agency (UBA), Berlin (Germany); Castaño, Argelia [Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid (Spain); Angerer, Jürgen; Koch, Holger M. [Institute for Prevention and Occupational Medicine of the German social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum (Germany); Esteban, Marta [Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid (Spain); and others

2015-08-15

Human biomonitoring (HBM) is an important tool, increasingly used for measuring true levels of the body burdens of environmental chemicals in the general population. In Europe, a harmonized HBM program was needed to open the possibility to compare levels across borders. To explore the prospect of a harmonized European HBM project, DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) was completed in 17 European countries. The basic measurements performed in all implemented countries of DEMOCOPHES included cadmium, cotinine and phthalate metabolites in urine and mercury in hair. In the Danish participants, significant correlations between mothers and children for mercury in hair and cotinine in urine were found. Mercury in hair was further significantly associated with intake of fish and area of residence. Cadmium was positively associated with BMI in mothers and an association between cadmium and cotinine was also found. As expected high cotinine levels were found in smoking mothers. For both mercury and cadmium significantly higher concentrations were found in the mothers compared to their children. In Denmark, the DEMOCOPHES project was co-financed by the Danish ministries of health, environment and food safety. The co-financing ministries agreed to finance a number of supplementary measurements of substances of current toxicological, public and regulatory interest. This also included blood sampling from the participants. The collected urine and blood samples were analyzed for a range of other persistent and non-persistent environmental chemicals as well as two biomarkers of effect. The variety of supplementary measurements gives the researchers further information on the exposure status of the participants and creates a basis for valuable knowledge on the pattern of exposure to various chemicals. - Highlights: • Levels of cadmium, mercury and cotinine in the Danish subpopulation are comparable to levels in the

Pregnancy outcome and cord blood cotinine level: A cross-sectional comparative study between secondhand smokers and non-secondhand smokers.

Science.gov (United States)

Abdullah, B; Muadz, B; Norizal, M N; Ismail, N; Kornain, N K; Kutty, M

2017-07-01

To compare the pregnancy outcome and cord blood cotinine levels between secondhand smokers and non-secondhand smokers. This was a cross-sectional comparative study in a Malaysian tertiary obstetric hospital involving 200 non-smoking pregnant women at term, of whom 100 were secondhand smokers and 100 were non-secondhand smokers. Those with multiple pregnancies, with a body mass index (BMI) of more than 30kg/m 2 or who delivered by Caesarean section were excluded. The participants' basic demographic details, delivery details, neonatal outcome and placental weight were recorded. Umbilical cord blood samples were obtained, and cord blood cotinine levels were measured with a Cotinine ELISA kit. The primary outcomes were baby's birth weight, length, and head circumference, Apgar score at 5min and placental weight. The secondary outcome was difference in cord blood cotinine levels between the two groups and the correlation of these differences with the neonatal outcome. The secondhand smoker group had significantly lower baby weight (2.94±0.31kg vs 3.05±0.40kg), head circumference (30.87±2.35cm vs 37.13±2.36cm), length (46.58±1.95cm vs 51.53±2.05cm) and placental weight (520±73.5g vs 596±61.3g) and significantly higher cord blood cotinine levels (16.35±12.84ng/mL vs 0.56±0.22ng/mL). Cord blood cotinine levels had significant negative correlations with placental weight (r=-0.461), baby's weight (r=-0.297), baby's head circumference (r=-0.501) and baby's length (r=-0.374). Secondhand smoke increases the incidence of adverse pregnancy outcomes (newborns'anthropometric measurements and placental weight) and causes higher cord blood cotinine levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Cotinine halts the advance of Alzheimer’s disease-like pathology and associated depressive-like behavior in Tg6799 mice

Directory of Open Access Journals (Sweden)

Sagar ePatel

2014-07-01

Full Text Available Alzheimer’s disease (AD is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ plaque pathology in the transgenic 6799 mice (Tg6799 mice when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in the Tg6799 mice when left untreated until after a more advanced stage of the disease’s development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aβ plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment, withheld until after a mid-level progression of AD-like pathology, reduced Aβ levels, Aβ plaques, and depressive-like behavior as well as dramatically improved working memory in Tg6799 mice to levels no different from control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B (Akt and the postsynaptic density protein 95 (PSD95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed.

Orally administered nicotine induces urothelial hyperplasia in rats and mice

International Nuclear Information System (INIS)

Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.

2014-01-01

mitogenic effect of nicotine and/or its metabolites

Measuring spatial and temporal trends of nicotine and alcohol consumption in Australia using wastewater-based epidemiology.

Science.gov (United States)

Lai, Foon Yin; Gartner, Coral; Hall, Wayne; Carter, Steve; O'Brien, Jake; Tscharke, Benjamin J; Been, Frederic; Gerber, Cobus; White, Jason; Thai, Phong; Bruno, Raimondo; Prichard, Jeremy; Kirkbride, K Paul; Mueller, Jochen F

2018-06-01

Tobacco and alcohol consumption remain priority public health issues world-wide. As participation in population-based surveys has fallen, it is increasingly challenging to estimate accurately the prevalence of alcohol and tobacco use. Wastewater-based epidemiology (WBE) is an alternative approach for estimating substance use at the population level that does not rely upon survey participation. This study examined spatio-temporal patterns in nicotine (a proxy for tobacco) and alcohol consumption in the Australian population via WBE. Daily wastewater samples (n = 164) were collected at 18 selected wastewater treatment plants across Australia, covering approximately 45% of the total population. Nicotine and alcohol metabolites in the samples were measured using liquid chromatography-tandem mass spectrometry. Daily consumption of nicotine and alcohol and its associated uncertainty were computed using Monte Carlo simulations. Nation-wide daily average and weekly consumption of these two substances were extrapolated using ordinary least squares and mixed-effect models. Nicotine and alcohol consumption was observed in all communities. Consumption of these substances in rural towns was three to four times higher than in urban communities. The spatial consumption pattern of these substances was consistent across the monitoring periods in 2014-15. Nicotine metabolites significantly reduced by 14-25% (P = 0.001-0.008) (2014-15) in some catchments. Alcohol consumption remained constant over the studied periods. Strong weekly consumption patterns were observed for alcohol but not nicotine. Nation-wide, the daily average consumption per person (aged 15-79 years) was estimated at approximately 2.5 cigarettes and 1.3-2.0 standard drinks (weekday-weekend) of alcohol. These estimates were close to the sale figure and apparent consumption, respectively. Wastewater-based epidemiology is a feasible method for objectively evaluating the geographic, temporal and weekly profiles of

Biosynthesis of NAD from nicotinic acid and nicotinamide by resting cells of Arthrobacter globiformis

International Nuclear Information System (INIS)

Kuwahara, Masaaki

1978-01-01

Isotopically labeled nicotinic acid and nicotinamide were incorporated into the metabolites of nicotinic acid-dependent pathway (Preiss-Handler pathway) of the NAD biosynthesis by resting cells of Arthrobacter globiformis. Azaserine and adenosine markedly stimulated the accumulation of NAD in the cells. Radioactive nicotinic acid and nicotinamide were also incorporated into an unknown compound when the cells were incubated in the presence of azaserine. Cell-free extract of the organism showed the NAD synthetase activity, which required ammonium ion and ATP for the amidation of deamido-NAD. Adenosine inhibited the enzyme activity. The organism possessed nicotinamidase, suggesting deamidation is the first step in the biosynthesis of NAD from nicotinamide. The activity was inhibited by NAD, NADP and NMN. (auth.)

Developmental hippocampal neuroplasticity in a model of nicotine replacement therapy during pregnancy and breastfeeding.

Directory of Open Access Journals (Sweden)

Ian Mahar

Full Text Available The influence of developmental nicotine exposure on the brain represents an important health topic in light of the popularity of nicotine replacement therapy (NRT as a smoking cessation method during pregnancy.In this study, we used a model of NRT during pregnancy and breastfeeding to explore the consequences of chronic developmental nicotine exposure on cerebral neuroplasticity in the offspring. We focused on two dynamic lifelong phenomena in the dentate gyrus (DG of the hippocampus that are highly sensitive to the environment: granule cell neurogenesis and long-term potentiation (LTP.Pregnant rats were implanted with osmotic mini-pumps delivering either nicotine or saline solutions. Plasma nicotine and metabolite levels were measured in dams and offspring. Corticosterone levels, DG neurogenesis (cell proliferation, survival and differentiation and glutamatergic electrophysiological activity were measured in pups.Juvenile (P15 and adolescent (P41 offspring exposed to nicotine throughout prenatal and postnatal development displayed no significant alteration in DG neurogenesis compared to control offspring. However, NRT-like nicotine exposure significantly increased LTP in the DG of juvenile offspring as measured in vitro from hippocampal slices, suggesting that the mechanisms underlying nicotine-induced LTP enhancement previously described in adult rats are already functional in pups.These results indicate that synaptic plasticity is disrupted in offspring breastfed by dams passively exposed to nicotine in an NRT-like fashion.

Studies on the metabolism and bioactivation of (S)-nicotine and beta-nicotyrine

International Nuclear Information System (INIS)

Shigenaga, M.K.

1989-01-01

(S)-Nicotine has long been suspected of contributing to the chronic toxicities associated with the use of cigarettes and other tobacco products. The possibility that (S)-nicotine could contribute to these chronic toxicities by causing irreversible damage to cellular macromolecules has prompted studies aimed at characterizing the metabolic pathways of (S)-nicotine that form reactive metabolites which bind covalently. In order to study these processes, (S)-5- 3 H-nicotine was synthesized by catalytic tritiolysis of (S)-5-bromonicotine with carrier-free tritium gas, purified by HPLC and characterized by tritium NMR, diode array VV and HPLC chromatographic analysis. The metabolism of (S)-5- 3 H-nicotine by rabbit liver and lung microsomal enzymes produced reactive intermediates which bound covalently to microsomal macromolecules in a time, NADPH and cytochrome P-450 dependent manner. The results of studies employing rabbit lung microsomes and agents which inhibit or alter the expression of the cytochrome P-450 isozyme composition in this tissue indicated that the covalent binding of (S)-nicotine requires (S)-nicotine Δ 1',5' -iminium ion as an obligate intermediate and the catalytic activity of lung cytochrome P-450 isozyme-2. Investigations of the effects of (S)-nicotine and related tobacco alkaloids on the oxidation of the Parkinson's disease inducing agent MPTP by the mitochondrial enzyme MAO-B were prompted by the inverse correlation between cigarette smoking and Parkinson's disease. In the author studies (S)-nicotine A 1',5' -iminium bisperchlorate inhibited the MAOB catalyzed oxidation of MPTP by a linear-mixed type mechanism. Subsequent studies identified β-nicotyrine as a MAO-B catalyzed oxidation product of (S)-nicotine A 1',5' -iminium ion

Distributions of pharmaceuticals in an urban estuary during both dry- and wet-weather conditions

Science.gov (United States)

Benotti, M.J.; Brownawell, Bruce J.

2007-01-01

Pharmaceuticals and selected major human metabolites are ubiquitous in Jamaica Bay, a wastewater-impacted estuary at concentrations in the low ng/L to low ??g/L range. Concentrations throughout the bay are often consistent with conservative behavior during dry-weather conditions, as evidenced by nearly linear concentration-salinity relationships. Deviation from conservative behavior is noted for some pharmaceuticals and attributed to microbial degradation. Caffeine, cotinine, nicotine, and paraxanthine were detected with the greatest analytical signal, although evidence is presented for in situ removal, especially for nicotine and caffeine. There is little evidence for significant removal of carbamazepine and sulfamethoxazole, suggesting they are more conservative and useful wastewater tracers. Immediately following heavy precipitation, which induced a combined sewer overflow (CSO) event, the concentrations of all compounds but acetaminophen and nicotine decreased or disappeared. This observation is consistent with a simple model illustrating the effect of precipitation has on pharmaceutical concentration in the wastewater stream, given the balance between dilution from rain and the bypass of treatment. ?? 2007 American Chemical Society.

Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study.

Science.gov (United States)

Goniewicz, Maciej L; Gawron, Michal; Smith, Danielle M; Peng, Margaret; Jacob, Peyton; Benowitz, Neal L

2017-02-01

Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device. © The Author 2016. 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.

Determination of a saliva cotinine cut-off to distinguish pregnant smokers from pregnant non-smokers

DEFF Research Database (Denmark)

Hegaard, Hanne K; Kjaergaard, Hanne; Møller, Lars F

2007-01-01

Objective validation of smoking status is necessary. Earlier studies have used saliva cotinine concentrations between 14.2 and 30 ng/ml as cut-off values to distinguish pregnant smokers from non-smokers. However, these cut-offs derive from studies including men and non-pregnant women....... This constitutes a problem, as recent studies have reported an accelerated metabolism in pregnant smokers. The aim of this study was to determine the optimum cut-off cotinine level distinguishing pregnant smokers from pregnant non-smokers....

Synthesis and positron emission tomography studies of C-11-labeled isotopomers and metabolites of GTS-21, a partial α7 nicotinic cholinergic agonist drug

International Nuclear Information System (INIS)

Kim, Sung Won; Ding Yushin; Alexoff, David; Patel, Vinal; Logan, Jean; Lin, K.-S.; Shea, Colleen; Muench, Lisa; Xu Youwen; Carter, Pauline; King, Payton; Constanzo, Jasmine R.; Ciaccio, James A.; Fowler, Joanna S.

2007-01-01

Introduction: (3E)-3-[(2,4-dimethoxyphenyl)methylene]-3,4,5,6-tetrahydro-2,3'-bipyridine (GTS-21), a partial α7 nicotinic acetylcholine receptor agonist drug, has recently been shown to improve cognition in schizophrenia and Alzheimer's disease. One of its two major demethylated metabolites, 4-OH-GTS-21, has been suggested to contribute to its therapeutic effects. Methods: We labeled GTS-21 in two different positions with carbon-11 ([2-methoxy- 11 C]GTS-21 and [4- 11 C]GTS-21) along with two corresponding demethylated metabolites ([2-methoxy- 11 C]4-OH-GTS-21 and [4-methoxy- 11 C]2-OH-GTS-21) for pharmacokinetic studies in baboons and mice with positron emission tomography (PET). Results: Both [2- 11 C]GTS-21 and [4-methoxy- 11 C]GTS-21 showed similar initial high rapid uptake in baboon brain, peaking from 1 to 3.5 min (0.027-0.038%ID/cc) followed by rapid clearance (t 1/2 11 C]GTS-21 continued to clear while [4-methoxy- 11 C]GTS-21 plateaued, suggesting the entry of a labeled metabolite into the brain. Comparison of the pharmacokinetics of the two labeled metabolites confirmed expected higher brain uptake and retention of [4-methoxy- 11 C]2-OH-GTS-21 (the labeled metabolite of [4-methoxy- 11 C]GTS-21) relative to [2-methoxy- 11 C]4-OH-GTS-21 (the labeled metabolite of [2-methoxy- 11 C]GTS-21), which had negligible brain uptake. Ex vivo studies in mice showed that GTS-21 is the major chemical form in the mouse brain. Whole-body dynamic PET imaging in baboon and mouse showed that the major route of excretion of C-11 is through the gallbladder. Conclusions: The major findings are as follows: (a) extremely rapid uptake and clearance of [2-methoxy- 11 C]GTS-21 from the brain, which may need to be considered in developing optimal dosing of GTS-21 for patients, and (b) significant brain uptake of 2-OH-GTS-21, suggesting that it might contribute to the therapeutic effects of GTS-21. This study illustrates the value of comparing different label positions and labeled

Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study

Science.gov (United States)

Gawron, Michal; Smith, Danielle M.; Peng, Margaret; Jacob, Peyton; Benowitz, Neal L.

2017-01-01

Introduction: Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. Methods: We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. Results: In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device. PMID:27613896

Cigarettes vs. e-cigarettes: Passive exposure at home measured by means of airborne marker and biomarkers

Energy Technology Data Exchange (ETDEWEB)

Ballbè, Montse [Tobacco Control Unit, Cancer Prevention and Control Program, Institut Català d' Oncologia, L’Hospitalet de Llobregat, Barcelona (Spain); Catalan Network of Smoke-free Hospitals, L' Hospitalet de Llobregat, Barcelona (Spain); Cancer Prevention and Control Group, Institut d' Investigació Biomèdica de Bellvitge – IDIBELL, L’Hospitalet de Llobregat, Barcelona (Spain); Addictions Unit, Institute of Neurosciences, Hospital Clínic de Barcelona – IDIBAPS, Barcelona (Spain); Department of Clinical Sciences, Universitat de Barcelona, Barcelona (Spain); Martínez-Sánchez, Jose M., E-mail: jmmartinez@iconcologia.net [Tobacco Control Unit, Cancer Prevention and Control Program, Institut Català d' Oncologia, L’Hospitalet de Llobregat, Barcelona (Spain); Cancer Prevention and Control Group, Institut d' Investigació Biomèdica de Bellvitge – IDIBELL, L’Hospitalet de Llobregat, Barcelona (Spain); Biostatistics Unit, Department of Basic Sciences, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Barcelona (Spain); Sureda, Xisca; Fu, Marcela [Tobacco Control Unit, Cancer Prevention and Control Program, Institut Català d' Oncologia, L’Hospitalet de Llobregat, Barcelona (Spain); Cancer Prevention and Control Group, Institut d' Investigació Biomèdica de Bellvitge – IDIBELL, L’Hospitalet de Llobregat, Barcelona (Spain); Department of Clinical Sciences, Universitat de Barcelona, Barcelona (Spain); and others

2014-11-15

Background: There is scarce evidence about passive exposure to the vapour released or exhaled from electronic cigarettes (e-cigarettes) under real conditions. The aim of this study is to characterise passive exposure to nicotine from e-cigarettes' vapour and conventional cigarettes' smoke at home among non-smokers under real-use conditions. Methods: We conducted an observational study with 54 non-smoker volunteers from different homes: 25 living at home with conventional smokers, 5 living with nicotine e-cigarette users, and 24 from control homes (not using conventional cigarettes neither e-cigarettes). We measured airborne nicotine at home and biomarkers (cotinine in saliva and urine). We calculated geometric mean (GM) and geometric standard deviations (GSD). We also performed ANOVA and Student's t tests for the log-transformed data. We used Bonferroni-corrected t-tests to control the family error rate for multiple comparisons at 5%. Results: The GMs of airborne nicotine were 0.74 μg/m{sup 3} (GSD=4.05) in the smokers’ homes, 0.13 μg/m{sup 3} (GSD=2.4) in the e-cigarettes users’ homes, and 0.02 μg/m{sup 3} (GSD=3.51) in the control homes. The GMs of salivary cotinine were 0.38 ng/ml (GSD=2.34) in the smokers’ homes, 0.19 ng/ml (GSD=2.17) in the e-cigarettes users’ homes, and 0.07 ng/ml (GSD=1.79) in the control homes. Salivary cotinine concentrations of the non-smokers exposed to e-cigarette's vapour at home (all exposed ≥2 h/day) were statistically significant different that those found in non-smokers exposed to second-hand smoke ≥2 h/day and in non-smokers from control homes. Conclusions: The airborne markers were statistically higher in conventional cigarette homes than in e-cigarettes homes (5.7 times higher). However, concentrations of both biomarkers among non-smokers exposed to conventional cigarettes and e-cigarettes’ vapour were statistically similar (only 2 and 1.4 times higher, respectively). The levels of airborne

Cigarettes vs. e-cigarettes: Passive exposure at home measured by means of airborne marker and biomarkers

International Nuclear Information System (INIS)

Ballbè, Montse; Martínez-Sánchez, Jose M.; Sureda, Xisca; Fu, Marcela

2014-01-01

Background: There is scarce evidence about passive exposure to the vapour released or exhaled from electronic cigarettes (e-cigarettes) under real conditions. The aim of this study is to characterise passive exposure to nicotine from e-cigarettes' vapour and conventional cigarettes' smoke at home among non-smokers under real-use conditions. Methods: We conducted an observational study with 54 non-smoker volunteers from different homes: 25 living at home with conventional smokers, 5 living with nicotine e-cigarette users, and 24 from control homes (not using conventional cigarettes neither e-cigarettes). We measured airborne nicotine at home and biomarkers (cotinine in saliva and urine). We calculated geometric mean (GM) and geometric standard deviations (GSD). We also performed ANOVA and Student's t tests for the log-transformed data. We used Bonferroni-corrected t-tests to control the family error rate for multiple comparisons at 5%. Results: The GMs of airborne nicotine were 0.74 μg/m 3 (GSD=4.05) in the smokers’ homes, 0.13 μg/m 3 (GSD=2.4) in the e-cigarettes users’ homes, and 0.02 μg/m 3 (GSD=3.51) in the control homes. The GMs of salivary cotinine were 0.38 ng/ml (GSD=2.34) in the smokers’ homes, 0.19 ng/ml (GSD=2.17) in the e-cigarettes users’ homes, and 0.07 ng/ml (GSD=1.79) in the control homes. Salivary cotinine concentrations of the non-smokers exposed to e-cigarette's vapour at home (all exposed ≥2 h/day) were statistically significant different that those found in non-smokers exposed to second-hand smoke ≥2 h/day and in non-smokers from control homes. Conclusions: The airborne markers were statistically higher in conventional cigarette homes than in e-cigarettes homes (5.7 times higher). However, concentrations of both biomarkers among non-smokers exposed to conventional cigarettes and e-cigarettes’ vapour were statistically similar (only 2 and 1.4 times higher, respectively). The levels of airborne nicotine and

Nicotine poisoning

Science.gov (United States)

Nicotine is found in: Chewing tobacco Cigarettes E-cigarettes Liquid nicotine Nicotine gum (Nicorette) Nicotine patches (Habitrol, Nicoderm) Pipe tobacco Some insecticides Tobacco leaves Note: This list may not be all-inclusive.

SU-F-I-66: The Effects of Nicotinic Agonists On Rat Hippocampal Glutamatergic Fluctuation by Using Proton Magnetic Resonance Spectroscopy at 9.4T

International Nuclear Information System (INIS)

Lim, S-I; Yoo, C-H; Song, K-H; Choe, B-Y; Woo, D-C

2016-01-01

Purpose: Nicotine exerts its effects through the activation of nicotinic acetylcholine receptors (nAChRs). Varenicline, a smoking cessation aid, is a partial agonist acting at the α4β2 nAChRs. Although nicotine and varenicline contribute to the reward system at the same time, the influence of the substances on hippocampal neurochemical changes has not been investigated yet. We therefore studied the effects of repeated nicotine exposure and varenicline administration on hippocampus of rats by using in vivo proton magnetic resonance spectroscopy (1H MRS) at 9.4T. Methods: Male Wistar rats (n = 11; mean body weight, 304.9 ± 9.9 g) were divided into 3 groups: control rats (control, n = 3); nicotine-induced rats (nicotine, n = 4); and nicotine- and varenicline-induced rats (varenicline, n = 4). Acquisition of in vivo MRS was conducted by using 9.4 T Agilent Scanner. The linear combination of model spectra (LCModel, version 6.3, Stephen W. Provencher) fitting software was used to quantify the metabolites in the frequency domain, using the basis metabolites. Results: In this study, the results show the tendency of increased Glu level in nicotine group than in the control and varenicline groups. Moreover, GSH and NAA levels tended to decrease in the nicotine group in comparison with those in the control and varenicline groups. Conclusion: These findings indicate that the hippocampus is integrally linked to the brain reward sensitization involved in addiction and glutamate release through mobilization of intracellular calcium stores. Further, oxidative stress and toxicity of nicotine on brain would cause the decline of GSH and NAA. In conclusion, we found that varenicline effectively inhibits the reward cycle.

SU-F-I-66: The Effects of Nicotinic Agonists On Rat Hippocampal Glutamatergic Fluctuation by Using Proton Magnetic Resonance Spectroscopy at 9.4T

Energy Technology Data Exchange (ETDEWEB)

Lim, S-I; Yoo, C-H [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of); Song, K-H; Choe, B-Y [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul (Korea, Republic of); Woo, D-C [Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul (Korea, Republic of)

2016-06-15

Purpose: Nicotine exerts its effects through the activation of nicotinic acetylcholine receptors (nAChRs). Varenicline, a smoking cessation aid, is a partial agonist acting at the α4β2 nAChRs. Although nicotine and varenicline contribute to the reward system at the same time, the influence of the substances on hippocampal neurochemical changes has not been investigated yet. We therefore studied the effects of repeated nicotine exposure and varenicline administration on hippocampus of rats by using in vivo proton magnetic resonance spectroscopy (1H MRS) at 9.4T. Methods: Male Wistar rats (n = 11; mean body weight, 304.9 ± 9.9 g) were divided into 3 groups: control rats (control, n = 3); nicotine-induced rats (nicotine, n = 4); and nicotine- and varenicline-induced rats (varenicline, n = 4). Acquisition of in vivo MRS was conducted by using 9.4 T Agilent Scanner. The linear combination of model spectra (LCModel, version 6.3, Stephen W. Provencher) fitting software was used to quantify the metabolites in the frequency domain, using the basis metabolites. Results: In this study, the results show the tendency of increased Glu level in nicotine group than in the control and varenicline groups. Moreover, GSH and NAA levels tended to decrease in the nicotine group in comparison with those in the control and varenicline groups. Conclusion: These findings indicate that the hippocampus is integrally linked to the brain reward sensitization involved in addiction and glutamate release through mobilization of intracellular calcium stores. Further, oxidative stress and toxicity of nicotine on brain would cause the decline of GSH and NAA. In conclusion, we found that varenicline effectively inhibits the reward cycle.

Nicotine Vapor Method to Induce Nicotine Dependence in Rodents.

Science.gov (United States)

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.

Plasma cotinine levels and pancreatic cancer in the EPIC cohort study

NARCIS (Netherlands)

Leenders, M.; Chuang, S.C.; Dahm, C.C.; Overvad, K.; Ueland, P.M.; Midttun, O.; Vollset, S.E.; Tjonneland, A.; Halkjaer, J.; Jenab, M.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Kaaks, R.; Canzian, F.; Boeing, H.; Weikert, C.; Trichopoulou, A.; Bamia, C.; Naska, A.; Palli, D.; Pala, V.; Mattiello, A.; Tumino, R.; Sacerdote, C.; Duijnhoven, F.J.B. van; Peeters, P.H.M.; Gils, C.H. van; Lund, E.; Rodriguez, L.; Duell, E.J.; Perez, M.J.; Molina-Montes, E.; Castano, J.M.; Barricarte, A.; Larrañaga, N.; Johansen, D.; Lindkvist, B.; Sund, M.; Ye, W.; Khaw, K.T.; Wareham, N.J.; Michaud, D.S.; Riboli, E.; Xun, W.W.; Allen, N.E.; Crowe, F.L.; Bueno-De-Mesquita, H.B.; Vineis, P.

2012-01-01

Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective

Did smokefree legislation in England reduce exposure to secondhand smoke among nonsmoking adults? Cotinine analysis from the Health Survey for England.

Science.gov (United States)

Sims, Michelle; Mindell, Jennifer S; Jarvis, Martin J; Feyerabend, Colin; Wardle, Heather; Gilmore, Anna

2012-03-01

On 1 July 2007, smokefree legislation was implemented in England, which made virtually all enclosed public places and workplaces smokefree. We examined trends in and predictors of secondhand smoke exposure among nonsmoking adults to determine whether exposure changed after the introduction of smokefree legislation and whether these changes varied by socioeconomic status (SES) and by household smoking status. We analyzed salivary cotinine data from the Health Survey for England that were collected in 7 of 11 annual surveys undertaken between 1998 and 2008. We conducted multivariate regression analyses to examine secondhand smoke exposure as measured by the proportion of nonsmokers with undetectable levels of cotinine and by geometric mean cotinine. Secondhand smoke exposure was higher among those exposed at home and among lower-SES groups. Exposure declined markedly from 1998 to 2008 (the proportion of participants with undetectable cotinine was 2.9 times higher in the last 6 months of 2008 compared with the first 6 months of 1998 and geometric mean cotinine declined by 80%). We observed a significant fall in exposure after legislation was introduced--the odds of having undetectable cotinine were 1.5 times higher [95% confidence interval (CI): 1.3, 1.8] and geometric mean cotinine fell by 27% (95% CI: 17%, 36%) after adjusting for the prelegislative trend and potential confounders. Significant reductions were not, however, seen in those living in lower-social class households or homes where smoking occurs inside on most days. We found that the impact of England's smokefree legislation on secondhand smoke exposure was above and beyond the underlying long-term decline in secondhand smoke exposure and demonstrates the positive effect of the legislation. Nevertheless, some population subgroups appear not to have benefitted significantly from the legislation. This finding suggests that these groups should receive more support to reduce their exposure.

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

Science.gov (United States)

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.

Synthesis and positron emission tomography studies of C-11-labeled isotopomers and metabolites of GTS-21, a partial {alpha}7 nicotinic cholinergic agonist drug

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States)]. E-mail: swkim@bnl.gov; Ding Yushin [Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Department of Radiology, Yale University School of Medicine, New Haven, CT 06520-8048 (United States); Alexoff, David [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Patel, Vinal [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Logan, Jean [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Lin, K.-S. [Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Shea, Colleen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Muench, Lisa [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Xu Youwen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Carter, Pauline [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); King, Payton [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Constanzo, Jasmine R. [Department of Chemistry, Fordham University, Bronx, NY 10458 (United States); Ciaccio, James A. [Department of Chemistry, Fordham University, Bronx, NY 10458 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 (United States); Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029 (United States)

2007-07-15

Introduction: (3E)-3-[(2,4-dimethoxyphenyl)methylene]-3,4,5,6-tetrahydro-2,3'-bipyridine (GTS-21), a partial {alpha}7 nicotinic acetylcholine receptor agonist drug, has recently been shown to improve cognition in schizophrenia and Alzheimer's disease. One of its two major demethylated metabolites, 4-OH-GTS-21, has been suggested to contribute to its therapeutic effects. Methods: We labeled GTS-21 in two different positions with carbon-11 ([2-methoxy-{sup 11}C]GTS-21 and [4-{sup 11}C]GTS-21) along with two corresponding demethylated metabolites ([2-methoxy-{sup 11}C]4-OH-GTS-21 and [4-methoxy-{sup 11}C]2-OH-GTS-21) for pharmacokinetic studies in baboons and mice with positron emission tomography (PET). Results: Both [2-{sup 11}C]GTS-21 and [4-methoxy-{sup 11}C]GTS-21 showed similar initial high rapid uptake in baboon brain, peaking from 1 to 3.5 min (0.027-0.038%ID/cc) followed by rapid clearance (t {sub 1/2}<15 min), resulting in low brain retention by 30 min. However, after 30 min, [2-methoxy-{sup 11}C]GTS-21 continued to clear while [4-methoxy-{sup 11}C]GTS-21 plateaued, suggesting the entry of a labeled metabolite into the brain. Comparison of the pharmacokinetics of the two labeled metabolites confirmed expected higher brain uptake and retention of [4-methoxy-{sup 11}C]2-OH-GTS-21 (the labeled metabolite of [4-methoxy-{sup 11}C]GTS-21) relative to [2-methoxy-{sup 11}C]4-OH-GTS-21 (the labeled metabolite of [2-methoxy-{sup 11}C]GTS-21), which had negligible brain uptake. Ex vivo studies in mice showed that GTS-21 is the major chemical form in the mouse brain. Whole-body dynamic PET imaging in baboon and mouse showed that the major route of excretion of C-11 is through the gallbladder. Conclusions: The major findings are as follows: (a) extremely rapid uptake and clearance of [2-methoxy-{sup 11}C]GTS-21 from the brain, which may need to be considered in developing optimal dosing of GTS-21 for patients, and (b) significant brain uptake of 2-OH-GTS-21

The shared role of oxidative stress and inflammation in major depressive disorder and nicotine dependence.

Science.gov (United States)

Nunes, Sandra Odebrecht Vargas; Vargas, Heber Odebrecht; Prado, Eduardo; Barbosa, Decio Sabbatini; de Melo, Luiz Picoli; Moylan, Steven; Dodd, Seetal; Berk, Michael

2013-09-01

Nicotine dependence is common in people with mood disorders; however the operative pathways are not well understood. This paper reviews the contribution of inflammation and oxidative stress pathways to the co-association of depressive disorder and nicotine dependence, including increased levels of pro-inflammatory cytokines, increased acute phase proteins, decreased levels of antioxidants and increased oxidative stress. These could be some of the potential pathophysiological mechanisms involved in neuroprogression. The shared inflammatory and oxidative stress pathways by which smoking may increase the risk for development of depressive disorders are in part mediated by increased levels of pro-inflammatory cytokines, diverse neurotransmitter systems, activation the hypothalamic-pituitary-adrenal (HPA) axis, microglial activation, increased production of oxidative stress and decreased levels of antioxidants. Depressive disorder and nicotine dependence are additionally linked imbalance between neuroprotective and neurodegenerative metabolites in the kynurenine pathway that contribute to neuroprogression. These pathways provide a mechanistic framework for understanding the interaction between nicotine dependence and depressive disorder. Copyright © 2013. Published by Elsevier Ltd.

Optimization of a Differential Ion Mobility Spectrometry-Tandem Mass Spectrometry Method for High-Throughput Analysis of Nicotine and Related Compounds: Application to Electronic Cigarette Refill Liquids.

Science.gov (United States)

Regueiro, Jorge; Giri, Anupam; Wenzl, Thomas

2016-06-21

Fast market penetration of electronic cigarettes is leading to an exponentially growing number of electronic refill liquids with different nicotine contents and an endless list of flavors. Therefore, rapid and simple methods allowing a fast screening of these products are necessary to detect harmful substances which can negatively impact the health of consumers. In this regard, the present work explores the capabilities of differential ion mobility spectrometry coupled to tandem mass spectrometry for high-throughput analysis of nicotine and 11 related compounds in commercial refill liquids for electronic cigarettes. The influence of main factors affecting the ion mobility separation, such as modifier types and concentration, separation voltage, and temperature, was systematically investigated. Despite small molecular weight differences among the studied compounds, a good separation was achieved in the ion mobility cell under the optimized conditions, which involved the use of ethanol as a polar gas-phase chemical modifier. Indeed, differential ion mobility was able to resolve (resolution >4) nicotine from its structural isomer anabasine without the use of any chromatographic separation. The quantitative performance of the proposed method was then evaluated, showing satisfactory precision (RSD ≤ 16%) and recoveries ranging from 85 to 100% for nicotine, and from 84 to 126% for the rest of the target analytes. Several commercial electronic cigarette refill liquids were analyzed to demonstrate the applicability of the method. In some cases, significant differences were found between labeled and measured levels of nicotine. Anatabine, cotinine, myosmine, and nornicotine were also found in some of the analyzed samples.

Nicotine Lozenges

Science.gov (United States)

Nicotine lozenges are used to help people stop smoking. Nicotine lozenges are in a class of medications called smoking cessation aids. They work by providing nicotine to your body to decrease the withdrawal symptoms ...

Harmane inhibits serotonergic dorsal raphe neurons in the rat.

Science.gov (United States)

Touiki, Khalid; Rat, Pascal; Molimard, Robert; Chait, Abderrahman; de Beaurepaire, Renaud

2005-11-01

Harmane and norharmane (two beta-carbolines) are tobacco components or products. The effects of harmane and norharmane on serotonergic raphe neurons remain unknown. Harmane and norharmane are inhibitors of the monoamine oxidases A (MAO-A) and B (MAO-B), respectively. To study the effects of harmane, norharmane, befloxatone (MAOI-A), and selegiline (MAOI-B) on the firing of serotonergic neurons. To compare the effects of these compounds to those of nicotine (whose inhibitory action on serotonergic neurons has been previously described). The effects of cotinine, a metabolite of nicotine known to interact with serotonergic systems, are also tested. In vivo electrophysiological recordings of serotonergic dorsal raphe neurons in the anaesthetized rat. Nicotine, harmane, and befloxatone inhibited serotonergic dorsal raphe neurons. The other compounds had no effects. The inhibitory effect of harmane (rapid and long-lasting inhibition) differed from that of nicotine (short and rapidly reversed inhibition) and from that of befloxatone (slow, progressive, and long-lasting inhibition). The inhibitory effects of harmane and befloxatone were reversed by the 5-HT1A antagonist WAY 100 635. Pretreatment of animals with p-chlorophenylalanine abolished the inhibitory effect of befloxatone, but not that of harmane. Nicotine, harmane, and befloxatone inhibit the activity of raphe serotonergic neurons. Therefore, at least two tobacco compounds, nicotine and harmane, inhibit the activity of serotonergic neurons. The mechanism by which harmane inhibits serotonergic dorsal raphe neurons is likely unrelated to a MAO-A inhibitory effect.

Nicotine self-administration and reinstatement of nicotine-seeking in male and female rats.

Science.gov (United States)

Feltenstein, Matthew W; Ghee, Shannon M; See, Ronald E

2012-03-01

Tobacco addiction is a relapsing disorder that constitutes a substantial worldwide health problem, with evidence suggesting that nicotine and nicotine-associated stimuli play divergent roles in maintaining smoking behavior in men and women. While animal models of tobacco addiction that utilize nicotine self-administration have become more widely established, systematic examination of the multiple factors that instigate relapse to nicotine-seeking have been limited. Here, we examined nicotine self-administration and subsequent nicotine-seeking in male and female Sprague-Dawley rats using an animal model of self-administration and relapse. Rats lever pressed for nicotine (0.03 and 0.05 mg/kg/infusion, IV) during 15 daily 2-h sessions, followed by extinction of lever responding. Once responding was extinguished, we examined the ability of previously nicotine-paired cues (tone+light), the anxiogenic drug yohimbine (2.5mg/kg, IP), a priming injection of nicotine (0.3mg/kg, SC), or combinations of drug+cues to reinstate nicotine-seeking. Both males and females readily acquired nicotine self-administration and displayed comparable levels of responding and intake at both nicotine doses. Following extinction, exposure to the previously nicotine-paired cues or yohimbine, but not the nicotine-prime alone, reinstated nicotine-seeking in males and females. Moreover, when combined with nicotine-paired cues, both yohimbine and nicotine enhanced reinstatement. No significant sex differences or estrous cycle dependent changes were noted across reinstatement tests. These results demonstrate the ability to reinstate nicotine-seeking with multiple modalities and that exposure to nicotine-associated cues during periods of a stressful state or nicotine can increase nicotine-seeking. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Urinary cotinine testing as pre-operative assessment of patients undergoing free flap surgery.

Science.gov (United States)

Reinbold, C; Rausky, J; Binder, J-P; Revol, M

2015-02-01

The identified risks of smoking with regard to operated tissues are so elevated that it is clearly dangerous to operate a smoker when the proposed intervention is neither vital nor urgent. The aim of this prospective study was to evaluate a simple method of screening patients who smoke, with the evaluation carried out before agreeing to carry out free tissue transfer. The purpose of the testing was to hold the patient responsible for his actions and minimize smoking-related complications by cancelling or postponing the planned operation if the patient continued to smoke. Screening included use of a standardized questionnaire at the first consultation and detection of cotinine using a urine test strip 7 days before the scheduled surgery. Patients were informed that in the event of positive results, the operation would not take place. A six-week preoperative smoking cessation period was mandatory. Seventy-six patients were included in this study. Among them, 25 (32.9%) reported being former smokers and 11 (14.5%) admitted in the initial questionnaire to being active smokers. Six patients (7.9%), including one self-reported non-smoker, tested positive for cotinine, and their operations were cancelled. Screening using a questionnaire and cotinine detection appeared to constitute a simple, inexpensive, rapid and reliable test. It allowed us to refuse to operate 6 non-compliant patients and was thereby likely to diminish morbidity in the free tissue transfers carried out in our ward. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

Science.gov (United States)

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 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.

PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators

International Nuclear Information System (INIS)

Lamba, Vishal; Yasuda, Kazuto; Lamba, Jatinder K.; Assem, Mahfoud; Davila, Julio; Strom, Stephen; Schuetz, Erin G.

2004-01-01

To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues

PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators.

Science.gov (United States)

Lamba, Vishal; Yasuda, Kazuto; Lamba, Jatinder K; Assem, Mahfoud; Davila, Julio; Strom, Stephen; Schuetz, Erin G

2004-09-15

To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues.

Specific determination of clinical and toxicological important substances in biological samples by LC-MS

International Nuclear Information System (INIS)

Mitulovic, G.

2001-02-01

This thesis of this dissertation is the specific determination of clinical and toxicological important substances in biological samples by LC-MS. Nicotine was determined in serum after application of nicotine plaster and nicotine nasal spray with HPLC-ESI-MS. Cotinine was determined direct in urine with HPLC-ESI-MS. Short time anesthetics were determined in blood and cytostatics were determined in liquor with HPLC-ESI-MS. (botek)

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

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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.

Nicotine response and nicotinic receptors in long-sleep and short-sleep mice.

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De Fiebre, C M; Medhurst, L J; Collins, A C

1987-01-01

Nicotine response and nicotinic receptor binding were characterized in long-sleep (LS) and short-sleep (SS) mice which have been selectively bred for differential "sleep-time" following ethanol administration. LS mice are more sensitive than SS mice to nicotine as measured by a battery of behavioral and physiological tests and as measured by sensitivity to nicotine-induced seizures. The greater sensitivity of the LS mice is not due to differences in binding of [3H]nicotine. Unlike inbred mouse strains which differ in sensitivity to nicotine-induced seizures, these selected mouse lines do not differ in levels of binding of [125I]alpha-bungarotoxin (BTX) in the hippocampus. Significant differences in BTX binding were found in the cerebellum and striatum. Although these two mouse lines do not differ in blood levels of nicotine following nicotine administration, they differ slightly in brain levels of nicotine indicating differential distribution of the drug. Since this distribution difference is much smaller than the observed behavioral differences, these mice probably differ in CNS sensitivity to nicotine; however, follow-up studies are necessary to test whether the differential response of these mice is due to subtle differences in distribution of nicotine to the brain.

Comparing salivary cotinine concentration in non-smokers from the general population and hospitality workers in Spain.

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Martínez-Sánchez, Jose M; Fu, Marcela; Pérez-Ríos, Mónica; López, María J; Moncada, Albert; Fernández, Esteve

2009-12-01

The objective was to compare the pattern of exposure to second-hand smoke (SHS) among non-smokers in the general population and in hospitality workers. We used the adult (16-64 years) non-smokers of two independent studies (general population and hospitality workers) in Spain. We assessed the exposure to SHS by means of questionnaire and salivary cotinine concentration. The salivary cotinine concentration by sex, age, educational level, day of week of saliva collection, and exposure to SHS were always higher in hospitality workers than in the general population. Our results indicated that non-smoker hospitality workers have higher levels of exposure to SHS than general population.

Acute effects of nicotine amplify accumbal neural responses during nicotine-taking behavior and nicotine-paired environmental cues.

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Karine Guillem

Full Text Available Nicotine self-administration (SA is maintained by several variables, including the reinforcing properties of nicotine-paired cues and the nicotine-induced amplification of those cue properties. The nucleus accumbens (NAc is implicated in mediating the influence of these variables, though the underlying neurophysiological mechanisms are not yet understood. In the present study, Long-Evans rats were trained to self-administer nicotine. During SA sessions each press of a lever was followed by an intravenous infusion of nicotine (30 µg/kg paired with a combined light-tone cue. Extracellular recordings of single-neuron activity showed that 20% of neurons exhibited a phasic change in firing during the nicotine-directed operant, the light-tone cue, or both. The phasic change in firing for 98% of neurons was an increase. Sixty-two percent of NAc neurons additionally or alternatively showed a sustained decrease in average firing during the SA session relative to a presession baseline period. These session decreases in firing were significantly less prevalent in a group of neurons that were activated during either the operant or the cue than in a group of neurons that were nonresponsive during those events (referred to as task-activated and task-nonactivated neurons, respectively. Moreover, the session decrease in firing was dose-dependent for only the task-nonactivated neurons. The data of the present investigation provide supportive correlational evidence for two hypotheses: (1 excitatory neurophysiological mechanisms mediate the NAc role in cue-maintenance of nicotine SA, and (2 a differential nicotine-induced inhibition of task-activated and task-nonactivated neurons mediates the NAc role in nicotine-induced amplification of cue effects on nicotine SA.

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

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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.

Human-health pharmaceutical compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

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Boyd, Robert A.; Furlong, Edward T.

2002-01-01

The U.S. Geological Survey and the National Park Service conducted a reconnaissance study to investigate the occurrence of selected human-health pharmaceutical compounds in water samples collected from Lake Mead on the Colorado River and Las Vegas Wash, a waterway used to transport treated wastewater from the Las Vegas metropolitan area to Lake Mead. Current research indicates many of these compounds can bioaccumulate and may adversely affect aquatic organisms by disrupting physiological processes, impairing reproductive functions, increasing cancer rates, contributing to the development of antibiotic-resistant strains of bacteria, and acting in undesirable ways when mixed with other substances. These compounds may be present in effluent because a high percentage of prescription and non-prescription drugs used for human-health purposes are excreted from the body as a mixture of parent compounds and degraded metabolite compounds; also, they can be released to the environment when unused products are discarded by way of toilets, sinks, and trash in landfills. Thirteen of 33 targeted compounds were detected in at least one water sample collected between October 2000 and August 2001. All concentrations were less than or equal to 0.20 micrograms per liter. The most frequently detected compounds in samples from Las Vegas Wash were caffeine, carbamazepine (used to treat epilepsy), cotinine (a metabolite of nicotine), and dehydronifedipine (a metabolite of the antianginal Procardia). Less frequently detected compounds in samples collected from Las Vegas Wash were antibiotics (clarithromycin, erythromycin, sulfamethoxazole, and trimethoprim), acetaminophen (an analgesic and anti-inflammatory), cimetidine (used to treat ulcers), codeine (a narcotic and analgesic), diltiazem (an antihypertensive), and 1,7-dimethylxanthine (a metabolite of caffeine). Fewer compounds were detected in samples collected from Lake Mead than from Las Vegas Wash. Caffeine was detected in all samples

Nicotinic plant poisoning.

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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

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

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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

Effect of In Vivo Nicotine Exposure on Chlorpyrifos Pharmacokinetics and Pharmacodynamics in Rats

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Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

2010-03-30

Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline (sc), and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. Physiologically based pharmacokinetic model simulations of CPF-oxon concentrations in blood and brain were predicted to be lower in nicotine treated groups, which were simulated by increasing the dearylation Vmax based upon previously conducted in vitro metabolism studies. These results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, further modulating brain AChE inhibition.

Nicotine replacement therapy

Science.gov (United States)

Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Before you start using a nicotine replacement product, here are some things to know: The more cigarettes you smoke, the higher the dose you may need to ...

Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette users.

Science.gov (United States)

Wagener, Theodore L; Floyd, Evan L; Stepanov, Irina; Driskill, Leslie M; Frank, Summer G; Meier, Ellen; Leavens, Eleanor L; Tackett, Alayna P; Molina, Neil; Queimado, Lurdes

2017-03-01

Electronic cigarettes' (e-cigarettes) viability as a public health strategy to end smoking will likely be determined by their ability to mimic the pharmacokinetic profile of a cigarette while also exposing users to significantly lower levels of harmful/potentially harmful constituents (HPHCs). The present study examined the nicotine delivery profile of third- (G3) versus second-generation (G2) e-cigarette devices and their users' exposure to nicotine and select HPHCs compared with cigarette smokers. 30 participants (10 smokers, 9 G2 and 11 G3 users) completed baseline questionnaires and provided exhaled carbon monoxide (eCO), saliva and urine samples. Following a 12-hour nicotine abstinence, G2 and G3 users completed a 2-hour vaping session (ie, 5 min, 10-puff bout followed by ad libitum puffing for 115 min). Blood samples, subjective effects, device characteristics and e-liquid consumption were assessed. Smokers, G2 and G3 users had similar baseline levels of cotinine, but smokers had 4 and 7 times higher levels of eCO (pe-cigarette liquids with significantly lower nicotine concentrations. During the vaping session, G3 users achieved significantly higher plasma nicotine concentrations than G2 users following the first 10 puffs (17.5 vs 7.3 ng/mL, respectively) and at 25 and 40 min of ad libitum use. G3 users consumed significantly more e-liquid than G2 users. Vaping urges/withdrawal were reduced following 10 puffs, with no significant differences between device groups. Under normal use conditions, both G2 and G3 devices deliver cigarette-like amounts of nicotine, but G3 devices matched the amount and speed of nicotine delivery of a conventional cigarette. Compared with cigarettes, G2 and G3 e-cigarettes resulted in significantly lower levels of exposure to a potent lung carcinogen and cardiovascular toxicant. These findings have significant implications for understanding the addiction potential of these devices and their viability/suitability as aids to

Biomarkers of passive smoking among Greek preschool children.

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Vardavas, Constantine I; Tzatzarakis, Manolis N; Tsatsakis, Aristeidis M; Athanasopoulos, Dimitrios; Balomenaki, Evaggelia; Linardakis, Manolis K; Kafatos, Anthony G

2006-12-01

Greece has the highest adult smoking prevalence in the European Union, affecting not only those who smoke but also threatening the health of those who are involuntarily exposed to passive smoke, especially young Greek children. The aim of this study was to quantify passive smoking biomarkers (serum nicotine and cotinine levels) among preschool children in Crete in relation to parental smoking habits. All children enrolled in kindergarten in western Crete (1,757 preschool children and 2,809 parents) were interviewed during the 2004-2005 Cretan health promotion programme out of which a sample of 81 children was randomly selected according to parental smoking status and blood samples for cotinine and nicotine assay were taken. The geometric means of serum nicotine values in children with both parents current smokers and in those with both parents non-smokers were 0.71 ng/ml (95%CI 0.62, 0.80) and 0.59 ng/ml (95%CI 0.49, 0.69), respectively, (p=0.073). Cotinine geometric mean values were found at 1.69 ng/ml (95%CI 0.93, 3.06) and 0.15 ng/ml (95%CI 0.09, 0.28), respectively, (pparents had also greater cotinine geometric mean values than boys (3.35 versus 0.85 ng/ml, respectively, p=0.018). Our findings prove that Greek preschool children, especially young girls, are exposed to substantial levels of passive smoke which therefore stresses the need for immediate action so as to prevent the predisposition and early addiction of Greek preschool children to tobacco.

Recent trends in children's exposure to second-hand smoke in England: cotinine evidence from the Health Survey for England.

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Jarvis, Martin J; Feyerabend, Colin

2015-09-01

To examine changes in children's exposure to second-hand tobacco smoke in England since 1998. Repeated cross-sectional surveys of the general population in England. The Health Survey for England. A total of 37 038 children participating in surveys from 1998 to 2012, 13 327 of whom were aged 4-15 years, had available cotinine and were confirmed non-smokers. The proportion of children with smoking parents; the proportion of children living in homes reported to be smoke-free; the proportion of children with undetectable concentrations of cotinine; linear and quadratic trend estimates of geometric mean cotinine across years. By 2012, 87.3% of children lived in a home that was smoke-free {97.2% [95% confidence interval (CI) = 95.9-98.1] when parents were non-smokers, 61.3% (95% CI = 55.5-66.8) when one or both parents smoked}. A total of 68.6% (95% CI = 64.3-72.6%) of children had undetectable cotinine in 2012, up from 14.3% (95% CI = 12.7-16.0%) in 1998. There was a highly significant linear trend across years (with a small but significant quadratic term) to declining geometric mean cotinine in all children from 0.52 ng/ml (95% CI = 0.48-0.57) in 1998 to 0.11 ng/ml (95% CI = 0.10-0.12) in 2012. Children from routine/manual backgrounds were more exposed, but experienced similar gains across years to those from non-manual backgrounds. In England, children's exposure to second-hand smoke has declined by 79% since 1998, with continuing progress since smoke-free legislation in 2007. An emerging social norm in England has led to the adoption of smoke-free homes not only when parents are non-smokers, but also when they smoke. © 2015 Society for the Study of Addiction.

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

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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 smokers. Cancer Epidemiol Biomarkers Prev; 25(6); 936-43. ©2016 AACR. ©2016 American Association for Cancer Research.

Acute and chronic in vivo effects of exposure to nicotine and propylene glycol from an E-cigarette on mucociliary clearance in a murine model.

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Laube, Beth L; Afshar-Mohajer, Nima; Koehler, Kirsten; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

2017-04-01

To determine the effect of an acute (1 week) and chronic (3 weeks) exposure to E-cigarette (E-cig) emissions on mucociliary clearance (MCC) in murine lungs. C57BL/6 male mice (age 10.5 ± 2.4 weeks) were exposed for 20 min/day to E-cigarette aerosol generated by a Joyetech 510-T ® E-cig containing either 0% nicotine (N)/propylene glycol (PG) for 1 week (n = 6), or 3 weeks (n = 9), or 2.4% N/PG for one week (n = 6), or 3 weeks (n = 9), followed by measurement of MCC. Control mice (n = 15) were not exposed to PG alone, or N/PG. MCC was assessed by gamma camera following aspiration of 99m technetium aerosol and was expressed as the amount of radioactivity removed from both lungs over 6 hours (MCC6hrs). Venous blood was assayed for cotinine levels in control mice and in mice exposed for 3-weeks to PG alone and N/PG. MCC6hrs in control mice and in mice acutely exposed to PG alone and N/PG was similar, averaging (±1 standard deviation) 8.6 ± 5.2%, 7.5 ± 2.8% and 11.2 ± 5.9%, respectively. In contrast, chronic exposure to PG alone stimulated MCC6hrs (17.2 ± 8.0)% and this stimulation was significantly blunted following chronic exposure to N/PG (8.7 ± 4.6)% (p < .05). Serum cotinine levels were <0.5 ng/ml in control mice and in mice exposed to PG alone, whereas, N/PG exposed mice averaged 14.6 ± 12.0 ng/ml. In this murine model, a chronic, daily, 20 min-exposure to N/PG, but not an acute exposure, slowed MCC, compared to exposure to PG alone and led to systemic absorption of nicotine.

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

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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.

Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco.

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Lorkiewicz, Pawel; Riggs, Daniel W; Keith, Rachel J; Conklin, Daniel J; Xie, Zhengzhi; Sutaria, Saurin; Lynch, Blake; Srivastava, Sanjay; Bhatnagar, Aruni

2018-06-02

Cigarette smoking is associated with an increase in cardiovascular disease risk, attributable in part to reactive volatile organic chemicals (VOCs). However, little is known about the extent of VOC exposure due to the use of other tobacco products. We recruited 48 healthy, tobacco users in four groups: cigarette, smokeless tobacco, occasional users of first generation e-cigarette and e-cigarette menthol and 12 healthy nontobacco users. After abstaining for 48 h, tobacco users used an assigned product. Urine was collected at baseline followed by five collections over a 3-h period to measure urinary metabolites of VOCs, nicotine, and tobacco alkaloids. Urinary levels of nicotine were ≃2-fold lower in occasional e-cigarette and smokeless tobacco users than in the cigarette smokers; cotinine and 3-hydroxycotinine levels were similar in all groups. Compared with nontobacco users, e-cigarette users had higher levels of urinary metabolites of xylene, cyanide, styrene, ethylbenzene, and benzene at baseline and elevated urinary levels of metabolites of xylene, N,N-dimethylformamide, and acrylonitrile after e-cigarette use. Metabolites of acrolein, crotonaldehyde, and 1,3-butadiene were significantly higher in smokers than in users of other products or nontobacco users. VOC metabolite levels in smokeless tobacco group were comparable to those found in nonusers with the exception of xylene metabolite-2-methylhippuric acid (2MHA), which was almost three fold higher than in nontobacco users. Smoking results in exposure to a range of VOCs at concentrations higher than those observed with other products, and first generation e-cigarette use is associated with elevated levels of N,N-dimethylformamide and xylene metabolites. This study shows that occasional users of first generation e-cigarettes have lower levels of nicotine exposure than the users of combustible cigarettes. Compared with combustible cigarettes, e-cigarettes, and smokeless tobacco products deliver lower levels of

Nicotine Withdrawal Disrupts Contextual Learning but Not Recall of Prior Contextual Associations: Implications for Nicotine Addiction

OpenAIRE

Portugal, George S.; Gould, Thomas J.

2008-01-01

Interactions between nicotine and learning could contribute to nicotine addiction. Although previous research indicates that nicotine withdrawal disrupts contextual learning, the effects of nicotine withdrawal on contextual memories acquired before withdrawal are unknown. The present study investigated whether nicotine withdrawal disrupted recall of prior contextual memories by examining the effects of nicotine withdrawal on recall of nicotine conditioned place preference (CPP) and contextual...

Thermochemical Properties of Nicotine Salts

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Riggs DM

2014-12-01

Full Text Available The thermal gravimetric analysis (TGA and differential scanning calorimetry (DSC results presented in this report clearly show that the thermal stability and the endothermic peak nicotine release temperatures are different for different nicotine salts and these temperatures appear to be linked to the general microstructural details of the salt itself. In addition, the peak nicotine release temperatures are highly dependent upon the sample size used. The heat of vaporization for neat (non-protonated nicotine is also sample-size dependent. The TGA data showed that the least stable of the salts tested at elevated temperatures was the liquid salt nicotine triacetate followed by the crystalline materials (e.g., nicotine gallate and finally, the amorphous salts (e.g., nicotine alginate. The DSC results revealed that the liquid and crystalline salts exhibit nicotine release endotherms that are strongly related to the sample weight being tested. The amorphous salts show nicotine endotherm peak temperatures that are nearly independent of the sample weight. The range of peak nicotine release temperatures varied depending upon the specific salts and the sample size from 83 oC to well over 200 oC. Based on these results, the evolution of nicotine from the nicotine salt should be expected to vary based on the composition of the salt, the details of its microstructure, and the amount of nicotine salt tested.

Mechanisms of metabonomic for a gateway drug: nicotine priming enhances behavioral response to cocaine with modification in energy metabolism and neurotransmitter level.

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Hongyu Li

Full Text Available Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. (1H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

Nicotine dependence and psychiatric disorders.

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

2003-01-01

Nicotine addiction is the single largest preventable cause of morbidity and mortality in the Western World. Smoking is not any more just a bad habit, but a substance addiction problem. The pharmacological aspects of nicotine show that this substance has a broad distribution in the different body compartnents, due mainly to its lipophilic characteristic. There are nicotinic receptors as members of cholinergic receptors' family. They are located in neuromuscular junction and in the central nervous system (CNS). Although they are similar, pentameric structure with an ionic channel to sodium, there are some differences in the protein chains characteristics. Repeated administration of nicotine in rats, results in the sensitization phenomenon, which produces increase in the behavioral locomotor activity response. It has been found that most psychostimulants-induced behavioral sensitization through a nicotine receptor activation. Nicotine receptors in CNS are located mainly in presynaptic membrane and in that way they regulated the release of several neurotransmitters, among them acetylcholine, dopamine, serotonin, and norepinephrine. In some activities like sleep-wake cycle, nicotine receptors have a functional significance. Nicotine receptor stimulation promotes wake time, reduces both, total sleep time and rapid eye movement sleep (REMS). About nicotine dependence, this substance full fills all the criteria for dependence and withdrawal syndrome. There are some people that have more vulnerability for to become nicotine dependent, those are psychiatric patients. Among them schizophrenia, major depression, anxiety disorders and attention deficit disorder, represent the best example in this area. Nicotine may have some beneficial effects, among them are some neuroprotective effects in disorders like Parkinson's disease, and Gilles de la Tourette' syndrome. Also there are several evidences that support the role of nicotine in cognitive improvement functions like attention

Natural history-driven, plant-mediated RNAi-based study reveals CYP6B46's role in a nicotine-mediated antipredator herbivore defense.

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Kumar, Pavan; Pandit, Sagar S; Steppuhn, Anke; Baldwin, Ian T

2014-01-28

Manduca sexta (Ms) larvae are known to efficiently excrete ingested nicotine when feeding on their nicotine-producing native hostplant, Nicotiana attenuata. Here we describe how ingested nicotine is co-opted for larval defense by a unique mechanism. Plant-mediated RNAi was used to silence a midgut-expressed, nicotine-induced cytochrome P450 6B46 (CYP6B46) in larvae consuming transgenic N. attenuata plants producing MsCYP6B46 dsRNA. These and transgenic nicotine-deficient plants were planted into native habitats to study the phenotypes of larvae feeding on these plants and the behavior of their predators. The attack-behavior of a native wolf spider (Camptocosa parallela), a major nocturnal predator, provided the key to understanding MsCYP6B46's function: spiders clearly preferred CYP6B46-silenced larvae, just as they had preferred larvae fed nicotine-deficient plants. MsCYP6B46 redirects a small amount (0.65%) of ingested nicotine from the midgut into hemolymph, from which nicotine is exhaled through the spiracles as an antispider signal. CYP6B46-silenced larvae were more susceptible to spider-attack because they exhaled less nicotine because of lower hemolymph nicotine concentrations. CYP6B46-silenced larvae were impaired in distributing ingested nicotine from midgut to hemolymph, but not in the clearing of hemolymph nicotine or in the exhalation of nicotine from hemolymph. MsCYP6B46 could be a component of a previously hypothesized pump that converts nicotine to a short-lived, transportable, metabolite. Other predators, big-eyed bugs, and antlion larvae were insensitive to this defense. Thus, chemical defenses, too toxic to sequester, can be repurposed for defensive functions through respiration as a form of defensive halitosis, and predators can assist the functional elucidation of herbivore genes.

Nicotine levels, withdrawal symptoms, and smoking reduction success in real world use: A comparison of cigarette smokers and dual users of both cigarettes and E-cigarettes.

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Jorenby, Douglas E; Smith, Stevens S; Fiore, Michael C; Baker, Timothy B

2017-01-01

To evaluate how experienced dual users used cigarettes and e-cigarettes in real-world use and under different levels of cigarette availability. Dual users (cigarettes+e-cigarettes; n=74) and a smoke-only group (just cigarettes; n=74) engaged in a 26-day study with two ad lib use intervals, a week of 75% cigarette reduction and three days of 100% cigarette reduction. After a week of ad lib use of products, all participants were asked to reduce smoking by 75% (dual users were free to use their e-cigarettes as they wished), followed by another week of ad lib use. All participants were then asked to reduce smoking by 100% (cessation) for three days. Primary outcomes were biological samples (carbon monoxide, urinary nicotine and cotinine). Participants also provided real-time reports of product use, craving, and withdrawal symptoms using a smartphone app. Dual users did not smoke fewer cigarettes than smoke-only participants during ad lib periods, but quadrupled their use of e-cigarettes during smoking reduction periods. Dual users were significantly more likely to maintain 100% reduction (97.1% vs. 81.2%). Amongst women, dual use was associated with higher nicotine levels and withdrawal suppression. Among a group of experienced dual users, e-cigarettes helped maintain smoking reduction and reduced some withdrawal symptoms, although both withdrawal symptoms and nicotine levels varied as a function of gender. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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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

Serum concentrations of kynurenines in adult patients with attention-deficit hyperactivity disorder (ADHD): a case-control study.

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Aarsland, Tore Ivar Malmei; Landaas, Elisabeth Toverud; Hegvik, Tor-Arne; Ulvik, Arve; Halmøy, Anne; Ueland, Per Magne; Haavik, Jan

2015-11-05

The essential amino acid tryptophan is catabolised mainly through the kynurenine pathway. Altered circulating levels of kynurenines have been reported in chronic inflammatory conditions and in several neuropsychiatric disorders, including depression and schizophrenia. Candidate gene studies suggest that genes related to the kynurenine catabolism may be associated with attention-deficit hyperactivity disorder (ADHD). Additionally, ADHD patients often report comorbid depression or anxiety. In this study we investigated serum levels of kynurenines in Norwegian adult ADHD patients and adult controls. We compared serum levels of tryptophan and the seven tryptophan metabolites kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid and quinolinic acid in 133 adult patients with ADHD and 131 adult controls (18-40 years). Riboflavin (vitamin B2), total vitamin B6 and the nicotine metabolite cotinine were also measured. Serum samples were analysed using mass spectrometry. Patients and controls reported comorbid disorders and past (childhood) and current ADHD symptoms using the Wender Utah Rating Scale (WURS) and the Adult ADHD Self-report Scale (ASRS). Logistic regression was used to calculate odds ratios for having an ADHD diagnosis for different serum levels of each metabolite. In addition, we used Spearman's correlation analysis to investigate the correlation between serum levels of tryptophan and kynurenines and ADHD symptom scores. Lower serum concentrations of tryptophan [odds ratio 0.61 (95 % confidence interval 0.45-0.83)], kynurenic acid [0.73 (0.53-0.99)], xanthurenic acid [0.65 (0.48-0.89)] and 3-hydroxyanthranilic acid [0.63 (0.46-0.85)], and higher levels of cotinine [7.17 (4.37-12.58)], were significantly associated with ADHD. After adjusting for tryptophan levels, only 3-hydroxyanthranilic acid and cotinine remained significant. Lower levels of tryptophan and kynurenine were also found to be correlated

Electronic Nicotine Delivery Systems.

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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.

Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP+ cells loss induced by restraint stress in mice.

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Perez-Urrutia, Nelson; Mendoza, Cristhian; Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Echeverria, Florencia; Grizzell, J Alex; Barreto, George E; Iarkov, Alexandre; Echeverria, Valentina

2017-09-01

Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the number and morphology of GFAP+ immunoreactive cells, in the hippocampus and frontal cortex of mice subjected to prolonged restraint stress. The results revealed that in addition to the mood and cognitive impairments, restraint stress induced a significant decrease in the number and arborization of GFAP+ cells in the brain of mice. Intranasal cotinine prevented these stress-derived symptoms and the morphological abnormalities GFAP+ cells in both of these brain regions which are critical to resilience to stress. The significance of these findings for the therapy of PTSD and depression is discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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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.

Self-Reported Environmental Tobacco Smoke Exposure and Avoidance Compared with Cotinine Confirmed Tobacco Smoke Exposure among Pregnant Women and Their Infants

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Adam Gregory Gavarkovs

2018-04-01

Full Text Available Background: Exposure to environmental tobacco smoke (ETS presents substantial health risks for pregnant women and newborn infants. Measurements of ETS include invasive and expensive biochemical tests, as well as less invasive and lower-cost, self-reported exposure and avoidance measures. Better understanding of self-report measures will help to select ETS assessments for evaluation. Methods: This analysis was conducted within the context of a tailored video intervention to reduce tobacco smoking and ETS exposure during pregnancy and after delivery in the control group sample of 147 nonsmoking women. Measurements of salivary cotinine concentration, self-reported ETS exposure, and avoidance behaviors were captured at 32 weeks’ gestation and 6 months postpartum. Results: Salivary cotinine concentration was significantly related to ETS avoidance among pregnant nonsmokers at 32 weeks’ gestation, but not ETS exposure. At 6 months postpartum, both the reported ETS exposure of the infant and maternal avoidance behaviors to reduce her infant’s exposure were associated with the infant’s salivary cotinine concentration. At 32 weeks’ gestation and 6 months postpartum, avoidance behaviors decreased as exposure increased. Discussion: This study suggests that for nonsmoking women during pregnancy, reports of tobacco smoke avoidance are more valid than reports of exposure. After delivery, self-reported ETS exposure or avoidance are associated with each other and the biochemical measurement of salivary cotinine. These results provide researchers and clinicians with evidence to support the inclusion of avoidance behaviors in the selection of ETS measures.

Different physiological and behavioural effects of e-cigarette vapour and cigarette smoke in mice.

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Ponzoni, L; Moretti, M; Sala, M; Fasoli, F; Mucchietto, V; Lucini, V; Cannazza, G; Gallesi, G; Castellana, C N; Clementi, F; Zoli, M; Gotti, C; Braida, D

2015-10-01

Nicotine is the primary addictive substance in tobacco smoke and electronic cigarette (e-cig) vapour. Methodological limitations have made it difficult to compare the role of the nicotine and non-nicotine constituents of tobacco smoke. The aim of this study was to compare the effects of traditional cigarette smoke and e-cig vapour containing the same amount of nicotine in male BALB/c mice exposed to the smoke of 21 cigarettes or e-cig vapour containing 16.8 mg of nicotine delivered by means of a mechanical ventilator for three 30-min sessions/day for seven weeks. One hour after the last session, half of the animals were sacrificed for neurochemical analysis, and the others underwent mecamylamine-precipitated or spontaneous withdrawal for the purposes of behavioural analysis. Chronic intermittent non-contingent, second-hand exposure to cigarette smoke or e-cig vapour led to similar brain cotinine and nicotine levels, similar urine cotinine levels and the similar up-regulation of α4β2 nicotinic acetylcholine receptors in different brain areas, but had different effects on body weight, food intake, and the signs of mecamylamine-precipitated and spontaneous withdrawal episodic memory and emotional responses. The findings of this study demonstrate for the first time that e-cig vapour induces addiction-related neurochemical, physiological and behavioural alterations. The fact that inhaled cigarette smoke and e-cig vapour have partially different dependence-related effects indicates that compounds other than nicotine contribute to tobacco dependence. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Determination of a saliva cotinine cut-off to distinguish pregnant smokers from pregnant non-smokers

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Hegaard, Hanne K; Kjaergaard, Hanne; Møller, Lars F

2007-01-01

Objective validation of smoking status is necessary. Earlier studies have used saliva cotinine concentrations between 14.2 and 30 ng/ml as cut-off values to distinguish pregnant smokers from non-smokers. However, these cut-offs derive from studies including men and non-pregnant women. This consti...

Decreased sensitivity to nicotine-induced seizures as a consequence of nicotine pretreatment in long-sleep and short-sleep mice.

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de Fiebre, C M; Collins, A C

1988-01-01

Male and female long-sleep (LS) and short-sleep (SS) mice were pretreated with a subseizure-producing dose of nicotine (2.0 mg/kg) 7.5, 15 and 30 minutes prior to challenge with seizure-producing doses of this drug. Nicotine pretreated animals were less susceptible to nicotine-induced seizures than were saline pretreated animals. The latency to seizure following nicotine challenge was greater in nicotine pretreated animals than in saline controls. Nicotine pretreated LS mice show a greater decrease in nicotine-induced seizure susceptibility than do nicotine pretreated SS mice. This decrease in seizure susceptibility is consistent with induction of nicotinic receptor desensitization via nicotine pretreatment. It is hypothesized that LS and SS mice might differ in sensitivity to nicotine in part because they differ in baseline levels of desensitized versus functional nicotinic receptors.

Measurement of the α4β2* nicotinic acetylcholine receptor ligand 2-[18F]Fluoro-A-85380 and its metabolites in human blood during PET investigation: a methodological study

International Nuclear Information System (INIS)

Sorger, Dietlind; Becker, Georg A.; Patt, Marianne; Schildan, Andreas; Grossmann, Udo; Schliebs, Reinhard; Seese, Anita; Kendziorra, Kai; Kluge, Magnus; Brust, Peter; Mukhin, Alexey G.; Sabri, Osama

2007-01-01

2-[ 18 F]fluoro-A-85380 (2-[ 18 F]FA) is a new radioligand for noninvasive imaging of α4β2* nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET) in human brain. In most cases, quantification of 2-[ 18 F]FA receptor binding involves measurement of free nonmetabolized radioligand concentration in blood. This requires an efficient and reliable method to separate radioactive metabolites from the parent compound. In the present study, three analytical methods, thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and solid phase extraction (SPE) have been tested. Reversed-phase TLC of deproteinized aqueous samples of plasma provides good estimates of 2-[ 18 F]FA and its metabolites. However, because of the decreased radioactivity in plasma samples, this method can be used in humans over the first 2 h after radioligand injection only. Reliable quantification of the parent radioligand and its main metabolites was obtained using reversed-phase HPLC, followed by counting of eluted fractions in a well gamma counter. Three main and five minor metabolites of 2-[ 18 F]FA were detected in human blood using this method. On average, the unchanged 2-[ 18 F]FA fraction in plasma of healthy volunteers measured at 14, 60, 120, 240 and 420 min after radioligand injection was 87.3±2.2%, 74.4±3%, 68.8±5%, 62.3±8% and 61.0±8%, respectively. In patients with neurodegenerative disorders, the values corresponding to the three last time points were significantly lower. The fraction of nonmetabolized 2-[ 18 F]FA in plasma determined using SPE did not differ significantly from that obtained by HPLC (+gamma counting) (n=73, r=.95). Since SPE is less time-consuming than HPLC and provides comparable results, we conclude that SPE appears to be the most suitable method for measurement of 2-[ 18 F]FA parent fraction during PET investigations

Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats.

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Simmons, Steven J; Gentile, Taylor A; Mo, Lili; Tran, Fionya H; Ma, Sisi; Muschamp, John W

2016-11-01

Tobacco smoking is the leading cause of preventable death in the United States. Nicotine is the principal psychoactive ingredient in tobacco that causes addiction. The structures governing nicotine addiction, including those underlying withdrawal, are still being explored. Nicotine withdrawal is characterized by negative affective and cognitive symptoms that enhance relapse susceptibility, and suppressed dopaminergic transmission from ventral tegmental area (VTA) to target structures underlies behavioral symptoms of nicotine withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking smokers at one-year post-cessation, and new targets are needed to more effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade, which is commonly used to precipitate withdrawal, on orexin neurons remain poorly investigated and present an attractive target for intervention. The present study sought to investigate the effects of nicotinic receptor blockade on hypothalamic orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate groups of rats were treated with either chronic nicotine or saline for 7-days at which point effects of mecamylamine or saline on somatic signs and anxiety-like behavior were assessed. Finally, tissue from rats was harvested for immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that nicotinic receptor blockade leads to reduced orexin cell activity, as indicated by lowered Fos-immunoreactivity, and suggest that this underlying cellular activity may be associated with symptoms of nicotine withdrawal as effects were most prominently observed in rats given chronic nicotine. We conclude from this study that orexin transmission becomes suppressed in rats upon nicotinic receptor blockade, and that behavioral symptoms associated

Reference Intervals for Urinary Cotinine Levels and the Influence of Sampling Time and Other Predictors on Its Excretion Among Italian Schoolchildren

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Carmela Protano

2018-04-01

Full Text Available (1 Background: Environmental Tobacco Smoke (ETS exposure remains a public health problem worldwide. The aims are to establish urinary (u- cotinine reference values for healthy Italian children, to evaluate the role of the sampling time and of other factors on children’s u-cotinine excretion. (2 Methods: A cross-sectional study was performed on 330 children. Information on participants was gathered by a questionnaire and u-cotinine was determined in two samples for each child, collected during the evening and the next morning. (3 Results: Reference intervals (as the 2.5th and 97.5th percentiles of the distribution in evening and morning samples were respectively equal to 0.98–4.29 and 0.91–4.50 µg L−1 (ETS unexposed and 1.39–16.34 and 1.49–20.95 µg L−1 (ETS exposed. No statistical differences were recovered between median values found in evening and morning samples, both in ETS unexposed and exposed. Significant predictors of u-cotinine excretions were ponderal status according to body mass index of children (β = 0.202; p-value = 0.041 for evening samples; β = 0.169; p-value = 0.039 for morning samples and paternal educational level (β = −0.258; p-value = 0.010; for evening samples; β = −0.013; p-value = 0.003 for morning samples. (4 Conclusions: The results evidenced the need of further studies for assessing the role of confounding factors on ETS exposure, and the necessity of educational interventions on smokers for rising their awareness about ETS.

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

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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.

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

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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*

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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

Airborne exposure and biological monitoring of bar and restaurant workers before and after the introduction of a smoking ban.

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Ellingsen, Dag G; Fladseth, Geir; Daae, Hanne L; Gjølstad, Merete; Kjaerheim, Kristina; Skogstad, Marit; Olsen, Raymond; Thorud, Syvert; Molander, Paal

2006-03-01

The aims were to assess the impact of a total smoking ban on the level of airborne contaminants and the urinary cotinine levels in the employees in bars and restaurants. In a follow up design, 13 bars and restaurants were visited before and after the implementation of a smoking ban. Ninety-three employees in the establishments were initially included into the study. The arithmetic mean concentration of nicotine and total dust declined from 28.3 microg m(-3) (range, 0.4-88.0) and 262 microg m(-3) (range, 52-662), respectively, to 0.6 microg m(-3) (range, not detected-3.7) and 77 microg m(-3) (range, not detected-261) after the smoking ban. The Pearson correlation coefficient between airborne nicotine and total dust was 0.86 (p introduction of a smoking ban in bars and restaurants. The urinary cotinine levels were reduced in non-smokers. The decline found in smokers may suggest a reduction in the amount of smoking after intervention. In non-smokers cotinine concentrations were higher based on urine sampled the morning after a shift than based on urine sampled immediately post-shift.

Toward a comprehensive long term nicotine policy.

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Gray, N; Henningfield, J E; Benowitz, N L; Connolly, G N; Dresler, C; Fagerstrom, K; Jarvis, M J; Boyle, P

2005-06-01

Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

Insight into nicotine addiction

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Sahil Handa

2017-01-01

Full Text Available The emergence of the epidemic of nicotine addiction in India and other nations is a global public health tragedy of untoward proportions. Smoking or chewing tobacco can seriously affect general, as well as oral health. Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke and addiction to nicotine is the proximate cause of these diseases. This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking. The pharmacologic reasons for nicotine use are an enhancement of mood, either directly or through relief of withdrawal symptoms and augmentation of mental or physical functions. Tobacco cessation is necessary to reduce morbidity and mortality related to tobacco use. Strategies for tobacco cessation involves 5A's and 5R's approach and pharmacotherapy. Dental professionals play an important role in helping patients to quit tobacco at the community and national levels, to promote tobacco prevention and control nicotine addiction. Dentists are in a unique position to educate and motivate patients concerning the hazards of tobacco to their oral and systemic health, and to provide intervention programs as a part of routine patient care.

Surveillance of smokeless tobacco nicotine, pH, moisture, and unprotonated nicotine content.

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Richter, Patricia; Spierto, Francis W

2003-12-01

Smokeless tobacco is a complex chemical mixture, including not only the components of the tobacco leaf but also chemicals added during the manufacturing process. Smokeless tobacco contains the addictive chemical nicotine and more than 20 cancer-causing chemicals, including the potent tobacco-specific nitrosamines. The National Toxicology Program of the National Institutes of Health has concluded that oral use of smokeless tobacco is a human carcinogen. Therefore, smokeless tobacco is not a safe alternative to cigarettes. In fact, smokeless tobacco use begins primarily during early adolescence and can lead to nicotine dependence and increased risk of becoming a cigarette smoker. Under the Comprehensive Smokeless Tobacco Health Education Act of 1986 (15 U.S.C. 4401 et seq., Pub. L. 99-252), tobacco manufacturers report annually to the Centers for Disease Control and Prevention (CDC) on the total nicotine, unprotonated nicotine, pH, and moisture content of their smokeless tobacco products. This information is considered "trade secret," or confidential, in accordance with 5 U.S.C. 552(b)(4) and 18 U.S.C. 1905 and cannot be released to the public. In an effort to provide consumers and researchers with information on the nicotine content of smokeless tobacco, CDC arranged for the analysis of popular brands of smokeless tobacco. The results of this CDC study show that pH is a primary factor in the amount of nicotine that is in the most readily absorbable, unprotonated form. Furthermore, this study found that the brands of moist snuff smokeless tobacco with the largest amount of unprotonated nicotine also are the most frequently sold brands.

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

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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.

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

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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.

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

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Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Roskams, Tania [Department of Morphology and Molecular Pathology, University of Leuven (Belgium); Oben, Jude A., E-mail: j.oben@ucl.ac.uk [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Department of Gastroenterology and Hepatology, Guy' s and St Thomas' Hospital, London SE1 7EH (United Kingdom)

2012-01-06

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

International Nuclear Information System (INIS)

Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI; Roskams, Tania; Oben, Jude A.

2012-01-01

Highlights: ► Cigarette smoke may induce liver fibrosis via nicotine receptors. ► Nicotine induces proliferation of hepatic stellate cells (HSCs). ► Nicotine activates hepatic fibrogenic pathways. ► Nicotine receptor antagonists attenuate HSC proliferation. ► 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 in 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-α2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-β1) 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 (α1, β1, delta and epsilon) and neuronal type (α3, α6, α7, β2 and β4) nAChR subunits at the mRNA level. Among these subunits, α3, α7, β1 and ε were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-α2 and TGF-β1 mRNA expression were significantly upregulated by nicotine and inhibited by mecamylamine. α1 and α3-nAChR mRNA expression was significantly upregulated in NASH fibrosis compared to normal livers. Conclusion: Nicotine at levels in smokers’ blood is pro-fibrogenic, through

A two-site, two-arm, 34-week, double-blind, parallel-group, randomized controlled trial of reduced nicotine cigarettes in smokers with mood and/or anxiety disorders: trial design and protocol

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Sophia I. Allen

2017-01-01

Full Text Available Abstract Background The U.S. Food and Drug Administration can set standards for cigarettes that could include reducing their nicotine content. Such a standard should improve public health without causing unintended serious consequences for sub-populations. This study evaluates the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure, and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders using a two-site, two-arm, double-blind, parallel group, randomized controlled trial (RCT in four phases over 34 weeks. Methods Adult smokers (N = 200 of 5 or more cigarettes per day will be randomized across two sites (Penn State and Massachusetts General. Participants must have not had a quit attempt in the prior month, nor be planning to quit in the next 6 months, meet criteria for a current or lifetime unipolar mood and/or anxiety disorder based on the structured Mini-International Neuropsychiatric Interview, and must not have an unstable medical or psychiatric condition. After a week of smoking their own cigarettes, participants receive two weeks of Spectrum research cigarettes with usual nicotine content (11.6 mg. After this baseline period, participants will be randomly assigned to continue smoking Spectrum research cigarettes that contain either (a Usual Nicotine Content (11.6 mg; or (b Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in five steps over 18 weeks. At the end of the randomization phase, participants will be offered the choice to either (a quit smoking with assistance, (b continue smoking free research cigarettes, or (c return to purchasing their own cigarettes, for the final 12 weeks of the study. The primary outcome measure is blood cotinine; key secondary outcomes are: exhaled carbon monoxide, urinary total NNAL- 4-(methylnitrosamino-1-(3-pyridyl-1-butanol and 1-hydroxypyrene, oxidative

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

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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

Nicotine concentration of e-cigarettes used by adolescents.

Science.gov (United States)

Morean, Meghan E; Kong, Grace; Cavallo, Dana A; Camenga, Deepa R; Krishnan-Sarin, Suchitra

2016-10-01

E-cigarettes are popular among youth, but little is known about the nicotine concentrations of e-liquids used by adolescents. In Spring, 2014, we conducted cross-sectional surveys in four Connecticut high schools and two middle schools. Among past-30-day e-cigarette users (n=513, 45% female, mean age 15.9 [SD=1.4]), we examined what nicotine concentration adolescents typically used in their e-cigarettes (range 0-30mg/mL and "I don't know"). We first examined whether age, sex, smoking status, e-cigarette use frequency, and/or e-cigarette acquisition source were associated with using nicotine-free e-liquid, nicotine e-liquid, or not knowing the e-liquid nicotine concentration. Among nicotine users (n=185), we then examined whether the aforementioned variables were associated with using higher nicotine concentrations. Adolescents reported using nicotine-free e-liquid (28.5%), nicotine e-liquid (37.4%), or not knowing their e-liquid nicotine concentration (34.1%). Nicotine users comprised more smokers and heavier e-cigarette users compared to nicotine-free e-liquid users and those who did not know their nicotine concentration. Nicotine users also comprised more males and were more likely to purchase e-cigarettes online or from tobacco shops compared to those who did not know their nicotine concentration. Among nicotine users, cigarette smoking, male sex, and purchasing e-cigarettes from tobacco shops predicted using higher nicotine concentrations. Adolescents reported using e-liquids with variable nicotine concentrations. Smokers, males, and those who purchased their own e-cigarettes reported using the highest nicotine levels. Of concern, many adolescents were unaware of the nicotine concentration in their e-liquid, raising concerns about inadvertent nicotine exposure among youth. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

High levels of PAH-metabolites in urine of e-waste recycling workers from Agbogbloshie, Ghana

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Feldt, Torsten, E-mail: feldt@bni-hamburg.de [Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht Str. 74, 20359 Hamburg (Germany); Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Moorenstr. 5, 40225 Düsseldorf (Germany); Fobil, Julius N., E-mail: jfobil@ug.edu.gh [Department of Biological, Environmental and Occupational Health Sciences, School of Public Health, University of Ghana, P.O. Box LG13, Legon (Ghana); Wittsiepe, Jürgen [Department of Hygiene, Social and Environmental Medicine, Ruhr-University Bochum, Universitätsstr. 150, 44801 Bochum (Germany); Wilhelm, Michael, E-mail: wilhelm@hygiene.rub.de [Department of Hygiene, Social and Environmental Medicine, Ruhr-University Bochum, Universitätsstr. 150, 44801 Bochum (Germany); Till, Holger, E-mail: holger.till@giz.de [GIZ — Regional Coordination Unit for HIV and TB (GiZ-ReCHT), 32 Cantonment Crescent, Cantonments, Accra (Ghana); Zoufaly, Alexander [Department of Medicine, Section Infectious Diseases and Tropical Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Burchard, Gerd, E-mail: gerd.burchard@bni-hamburg.de [Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht Str. 74, 20359 Hamburg (Germany); Department of Medicine, Section Infectious Diseases and Tropical Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Göen, Thomas, E-mail: thomas.goeen@ipasum.med.uni-erlangen.de [Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Schillerstr. 25/29, 91054 Erlangen (Germany)

2014-01-01

The informal recycling of electronic waste (e-waste) is an emerging source of environmental pollution in Africa. Among other toxins, polycyclic aromatic hydrocarbons (PAHs) are a major health concern for exposed individuals. In a cross-sectional study, the levels of PAH metabolites in the urine of individuals working on one of the largest e-waste recycling sites of Africa, and in controls from a suburb of Accra without direct exposure to e-waste recycling activities, were investigated. Socioeconomic data, basic health data and urine samples were collected from 72 exposed individuals and 40 controls. In the urine samples, concentrations of the hydroxylate PAH metabolites (OH-PAH) 1-hydroxyphenanthrene (1-OH-phenanthrene), the sum of 2- and 9-hydroxyphenanthrene (2-/9-OH-phenanthrene), 3-hydroxyphenanthrene (3-OH-phenanthrene), 4-hydroxyphenanthrene (4-OH-phenanthrene) and 1-hydroxypyrene (1-OH-pyrene), as well as cotinine and creatinine, were determined. In the exposed group, median urinary concentrations were 0.85 μg/g creatinine for 1-OH-phenanthrene, 0.54 μg/g creatinine for 2-/9-OH-phenanthrene, 0.99 μg/g creatinine for 3-OH-phenanthrene, 0.22 μg/g creatinine for 4-OH-phenanthrene, and 1.33 μg/g creatinine for 1-OH-pyrene, all being significantly higher compared to the control group (0.55, 0.37, 0.63, 0.11 and 0.54 μg/g creatinine, respectively). Using a multivariate linear regression analysis including sex, cotinine and tobacco smoking as covariates, exposure to e-waste recycling activities was the most important determinant for PAH exposure. On physical examination, pathological findings were rare, but about two thirds of exposed individuals complained about cough, and one quarter about chest pain. In conclusion, we observed significantly higher urinary PAH metabolite concentrations in individuals who were exposed to e-waste recycling compared to controls who were not exposed to e-waste recycling activities. The impact of e-waste recycling on exposure to

High levels of PAH-metabolites in urine of e-waste recycling workers from Agbogbloshie, Ghana

International Nuclear Information System (INIS)

Feldt, Torsten; Fobil, Julius N.; Wittsiepe, Jürgen; Wilhelm, Michael; Till, Holger; Zoufaly, Alexander; Burchard, Gerd; Göen, Thomas

2014-01-01

The informal recycling of electronic waste (e-waste) is an emerging source of environmental pollution in Africa. Among other toxins, polycyclic aromatic hydrocarbons (PAHs) are a major health concern for exposed individuals. In a cross-sectional study, the levels of PAH metabolites in the urine of individuals working on one of the largest e-waste recycling sites of Africa, and in controls from a suburb of Accra without direct exposure to e-waste recycling activities, were investigated. Socioeconomic data, basic health data and urine samples were collected from 72 exposed individuals and 40 controls. In the urine samples, concentrations of the hydroxylate PAH metabolites (OH-PAH) 1-hydroxyphenanthrene (1-OH-phenanthrene), the sum of 2- and 9-hydroxyphenanthrene (2-/9-OH-phenanthrene), 3-hydroxyphenanthrene (3-OH-phenanthrene), 4-hydroxyphenanthrene (4-OH-phenanthrene) and 1-hydroxypyrene (1-OH-pyrene), as well as cotinine and creatinine, were determined. In the exposed group, median urinary concentrations were 0.85 μg/g creatinine for 1-OH-phenanthrene, 0.54 μg/g creatinine for 2-/9-OH-phenanthrene, 0.99 μg/g creatinine for 3-OH-phenanthrene, 0.22 μg/g creatinine for 4-OH-phenanthrene, and 1.33 μg/g creatinine for 1-OH-pyrene, all being significantly higher compared to the control group (0.55, 0.37, 0.63, 0.11 and 0.54 μg/g creatinine, respectively). Using a multivariate linear regression analysis including sex, cotinine and tobacco smoking as covariates, exposure to e-waste recycling activities was the most important determinant for PAH exposure. On physical examination, pathological findings were rare, but about two thirds of exposed individuals complained about cough, and one quarter about chest pain. In conclusion, we observed significantly higher urinary PAH metabolite concentrations in individuals who were exposed to e-waste recycling compared to controls who were not exposed to e-waste recycling activities. The impact of e-waste recycling on exposure to

Nicotine reward and affective nicotine withdrawal signs are attenuated in calcium/calmodulin-dependent protein kinase IV knockout mice.

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Kia J Jackson

Full Text Available The influx of Ca(2+ through calcium-permeable nicotinic acetylcholine receptors (nAChRs leads to activation of various downstream processes that may be relevant to nicotine-mediated behaviors. The calcium activated protein, calcium/calmodulin-dependent protein kinase IV (CaMKIV phosphorylates the downstream transcription factor cyclic AMP response element binding protein (CREB, which mediates nicotine responses; however the role of CaMKIV in nicotine dependence is unknown. Given the proposed role of CaMKIV in CREB activation, we hypothesized that CaMKIV might be a crucial molecular component in the development of nicotine dependence. Using male CaMKIV genetically modified mice, we found that nicotine reward is attenuated in CaMKIV knockout (-/- mice, but cocaine reward is enhanced in these mice. CaMKIV protein levels were also increased in the nucleus accumbens of C57Bl/6 mice after nicotine reward. In a nicotine withdrawal assessment, anxiety-related behavior, but not somatic signs or the hyperalgesia response are attenuated in CaMKIV -/- mice. To complement our animal studies, we also conducted a human genetic association analysis and found that variants in the CaMKIV gene are associated with a protective effect against nicotine dependence. Taken together, our results support an important role for CaMKIV in nicotine reward, and suggest that CaMKIV has opposing roles in nicotine and cocaine reward. Further, CaMKIV mediates affective, but not physical nicotine withdrawal signs, and has a protective effect against nicotine dependence in human genetic association studies. These findings further indicate the importance of calcium-dependent mechanisms in mediating behaviors associated with drugs of abuse.

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

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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

Neuronal nicotinic acetylcholine receptors: Common molecular substrates of nicotine and alcohol dependence

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Linzy M. Hendrickson

2013-04-01

Full Text Available Alcohol and nicotine are often co-abused. As many as 80-95% of alcoholics are also smokers, suggesting that ethanol and nicotine, the primary addictive component of tobacco smoke, may functionally interact in the central nervous system and/or share a common mechanism of action. While nicotine initiates dependence by binding to and activating neuronal nicotinic acetylcholine receptors (nAChRs, ligand-gated cation channels normally activated by endogenous acetylcholine (ACh, ethanol is much less specific with the ability to modulate multiple gene products including those encoding voltage-gated ion channels, and excitatory/inhibitory neurotransmitter receptors. However, emerging data indicate that ethanol interacts with nAChRs, both directly and indirectly, in the mesocorticolimbic dopaminergic (DAergic reward circuitry to affect brain reward systems. Like nicotine, ethanol activates DAergic neurons of the ventral tegmental area (VTA which project to the nucleus accumbens (NAc. Blockade of VTA nAChRs reduces ethanol-mediated activation of DAergic neurons, NAc DA release, consumption, and operant responding for ethanol in rodents. Thus, ethanol may increase ACh release into the VTA driving activation of DAergic neurons through nAChRs. In addition, ethanol potentiates distinct nAChR subtype responses to ACh and nicotine in vitro and in DAergic neurons. The smoking cessation therapeutic and nAChR partial agonist, varenicline, reduces alcohol consumption in heavy drinking smokers and rodent models of alcohol consumption. Finally, single nucleotide polymorphisms in nAChR subunit genes are associated with alcohol dependence phenotypes and smoking behaviors in human populations. Together, results from preclinical, clinical, and genetic studies indicate that nAChRs may have an inherent role in the abusive properties of ethanol, as well as in nicotine and alcohol co-dependence.

Genotoxicity study on nicotine and nicotine-derived nitrosamine by accelerator mass spectrometry

International Nuclear Information System (INIS)

Li, X.S.; Wang, H.F.; Shi, J.Y.; Wang, X.Y.; Liu, Y.F.; Li, K.; Lu, X.Y.; Wang, J.J.; Liu, K.X.; Guo, Z.Y.

1997-01-01

The authors have studied DNA adduction with 14 C-labelled nicotine and nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by accelerator mass spectrometry (AMS) in mouse liver at doses equivalent to low-level exposure of humans. The dose ranges of nicotine and NNK administered were from 0.4 μg to 4.0 x 10 2 μg·kg -1 , and from 0.1 μg to 2.0 x 10 4 μg·kg -1 , respectively. In the exposure of mice to either nicotine or NNK, the number of DNA adducts increased linearly with increasing dose. The detection limit of DNA adducts was 1 adduct per 10 11 nucleotide molecules. This limit is 1-4 orders of magnitude lower than that of other techniques used for quantification of DNA adducts. The results of the animal experiments enabled us to speculate that nicotine is a potential carcinogen. According to the procedure for 14 C-labelled-NNK synthesis, the authors discuss the ultimate chemical speciation of NNK bound to DNA. From the animal tests the authors derived a directly perceivable relation between tobacco consumption and DNA adduction as the carcinogenic risk assessment

Pathogenesis of Abdominal Aortic Aneurysms: Role of Nicotine and Nicotinic Acetylcholine Receptors

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Zong-Zhuang Li

2012-01-01

Full Text Available Inflammation, proteolysis, smooth muscle cell apoptosis, and angiogenesis have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs, although the well-defined initiating mechanism is not fully understood. Matrix metalloproteinases (MMPs such as MMP-2 and -9 and other proteinases degrading elastin and extracellular matrix are the critical pathogenesis of AAAs. Among the risk factors of AAAs, cigarette smoking is an irrefutable one. Cigarette smoke is practically involved in various aspects of the AAA pathogenesis. Nicotine, a major alkaloid in tobacco leaves and a primary component in cigarette smoke, can stimulate the MMPs expression by vascular SMCs, endothelial cells, and inflammatory cells in vascular wall and induce angiogenesis in the aneurysmal tissues. However, for the inflammatory and apoptotic processes in the pathogenesis of AAAs, nicotine seems to be moving in just the opposite direction. Additionally, the effects of nicotine are probably dose dependent or associated with the exposure duration and may be partly exerted by its receptors—nicotinic acetylcholine receptors (nAChRs. In this paper, we will mainly discuss the pathogenesis of AAAs involving inflammation, proteolysis, smooth muscle cell apoptosis and angiogenesis, and the roles of nicotine and nAChRs.

High Level of Tobacco Carcinogen-Derived DNA Damage in Oral Cells Is an Independent Predictor of Oral/Head and Neck Cancer Risk in Smokers.

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Khariwala, Samir S; Ma, Bin; Ruszczak, Chris; Carmella, Steven G; Lindgren, Bruce; Hatsukami, Dorothy K; Hecht, Stephen S; Stepanov, Irina

2017-09-01

Exposure to tobacco-specific nitrosamines (TSNA) and polycyclic aromatic hydrocarbons (PAH) is recognized to play an important role in the development of oral/head and neck squamous cell cancer (HNSCC). We recently reported higher levels of TSNA-associated DNA adducts in the oral cells of smokers with HNSCC as compared with cancer-free smokers. In this study, we further investigated the tobacco constituent exposures in the same smokers to better understand the potential causes for the elevated oral DNA damage in smokers with HNSCC. Subjects included cigarette smokers with HNSCC (cases, n = 30) and cancer-free smokers (controls, n = 35). At recruitment, tobacco/alcohol use questionnaires were completed, and urine and oral cell samples were obtained. Analysis of urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and N '-Nitrosonornicotine (NNN; TSNA biomarkers), 1-hydroxypyrene (1-HOP, a PAH), cotinine, 3'-hydroxycotinine, and the nicotine metabolite ratio (NMR) were performed. Cases and controls differed in mean age, male preponderance, and frequency of alcohol consumption (but not total alcoholic drinks). Univariate analysis revealed similar levels of NNN, 1-HOP, and cotinine between groups but, as reported previously, significantly higher DNA adduct formation in the cases. Multiple regression adjusting for potential confounders showed persistent significant difference in DNA adduct levels between cases and controls [ratio of geometric means, 20.0; 95% CI, 2.7-148.6). Our cohort of smokers with HNSCC demonstrates higher levels of TSNA-derived oral DNA damage in the setting of similar exposure to nicotine and tobacco carcinogens. Among smokers, DNA adduct formation may act as a predictor of eventual development of HNSCC that is independent of carcinogen exposure indicators. Cancer Prev Res; 10(9); 507-13. ©2017 AACR See related editorial by Johnson and Bauman, p. 489 . ©2017 American Association for Cancer Research.

Habenular expression of rare missense variants of the β4 nicotinic receptor subunit alters nicotine consumption

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Marta A Ślimak

2014-01-01

Full Text Available The CHRNA5-CHRNA3-CHRNB4 gene cluster, encoding the α5, α3 and β4 nicotinic acetylcholine receptor (nAChR subunits, has been linked to nicotine dependence. The habenulo-interpeduncular (Hb-IPN tract is particularly enriched in α3β4 nAChRs. We recently showed that modulation of these receptors in the medial habenula (MHb in mice altered nicotine consumption. Given that β4 is rate-limiting for receptor activity and that single nucleotide polymorphisms (SNPs in CHRNB4 have been linked to altered risk of nicotine dependence in humans, we were interested in determining the contribution of allelic variants of β4 to nicotine receptor activity in the MHb. We screened for missense SNPs with allele frequencies > 0.0005 and introduced the corresponding substitutions in Chrnb4. Fourteen variants were analyzed by co-expression with α3. We found that β4A90I and β4T374I variants, previously shown to associate with reduced risk of smoking, and an additional variant β4D447Y, significantly increased nicotine-evoked current amplitudes, while β4R348C, the mutation most frequently encountered in sporadic amyotrophic lateral sclerosis (sALS, showed reduced nicotine currents. We employed lentiviruses to express β4 or β4 variants in the MHb. Immunoprecipitation studies confirmed that β4 lentiviral-mediated expression leads to specific upregulation of α3β4 but not β2 nAChRs in the Mhb. Mice injected with the β4-containing virus showed pronounced aversion to nicotine as previously observed in transgenic Tabac mice overexpressing Chrnb4 at endogenous sites including the MHb. Habenular expression of the β4 gain-of-function allele T374I also resulted in strong aversion, while transduction with the β4 loss-of function allele R348C failed to induce nicotine aversion. Altogether, these data confirm the critical role of habenular β4 in nicotine consumption, and identify specific SNPs in CHRNB4 that modify nicotine-elicited currents and alter nicotine

NICOTINE EFFECTS ON THE MOTOR ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

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Several studies in the literature have shown that exposure of mice and rats to nicotine early in development alters its effects when the rodents are subsequently challenged with nicotine. Anatoxin-a is a nicotinic agonist produced by several genera of cyanobacteria, and has caus...

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

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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

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

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Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models

Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

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Bai, Xiyuan; Stitzel, Jerry A; Bai, An; Zambrano, Cristian A; Phillips, Matthew; Marrack, Philippa; Chan, Edward D

2017-09-01

Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB), but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we used a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR)-mecamylamine-as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages, as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-β. Naive mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater numbers of viable MTB recovered with increased IL-10 production and urea production, but no difference in secreted nitric oxide as compared with macrophages cocultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subverting macrophage control of MTB infection.

Measurement of nicotine in household dust

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Kim, Sungroul; Aung, Ther; Berkeley, Emily; Diette, Gregory B.; Breysse, Patrick N.

2008-01-01

An analytical method of measuring nicotine in house dust was optimized and associations among three secondhand smoking exposure markers were evaluated, i.e., nicotine concentrations of both house dust and indoor air, and the self-reported number of cigarettes smoked daily in a household. We obtained seven house dust samples from self-reported nonsmoking homes and 30 samples from smoking homes along with the information on indoor air nicotine concentrations and the number of cigarettes smoked daily from an asthma cohort study conducted by the Johns Hopkins Center for Childhood Asthma in the Urban Environment. House dust nicotine was analyzed by isotope dilution gas chromatography-mass spectrometry (GC/MS). Using our optimized method, the median concentration of nicotine in the dust of self-reported nonsmoking homes was 11.7 ng/mg while that of smoking homes was 43.4 ng/mg. We found a substantially positive association (r=0.67, P<0.0001) between house dust nicotine concentrations and the numbers of cigarettes smoked daily. Optimized analytical methods showed a feasibility to detect nicotine in house dust. Our results indicated that the measurement of nicotine in house dust can be used potentially as a marker of longer term SHS exposure

Rationalization of a nanoparticle-based nicotine nanovaccine as an effective next-generation nicotine vaccine: A focus on hapten localization.

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Zhao, Zongmin; Hu, Yun; Harmon, Theresa; Pentel, Paul; Ehrich, Marion; Zhang, Chenming

2017-09-01

A lipid-polymeric hybrid nanoparticle-based next-generation nicotine nanovaccine was rationalized in this study to combat nicotine addiction. A series of nanovaccines, which had nicotine-haptens localized on carrier protein (LPKN), nanoparticle surface (LPNK), or both (LPNKN), were designed to study the impact of hapten localization on their immunological efficacy. All three nanovaccines were efficiently taken up and processed by dendritic cells. LPNKN induced a significantly higher immunogenicity against nicotine and a significantly lower anti-carrier protein antibody level compared to LPKN and LPNK. Meanwhile, it was found that the anti-nicotine antibodies elicited by LPKN and LPNKN bind nicotine stronger than those elicited by LPKN, and LPNK and LPNKN resulted in a more balanced Th1-Th2 immunity than LPKN. Moreover, LPNKN exhibited the best ability to block nicotine from entering the brain of mice. Collectively, the results demonstrated that the immunological efficacy of the hybrid nanoparticle-based nicotine vaccine could be enhanced by modulating hapten localization, providing a promising strategy to combatting nicotine addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

2011-11-18

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

International Nuclear Information System (INIS)

Zago, A.; Leão, R.M.; Carneiro-de-Oliveira, P.E.; Marin, M.T.; Cruz, F.C.; Planeta, C.S.

2011-01-01

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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A. Zago

2012-01-01

Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Urinary Excretion of Niacin Metabolites in Humans After Coffee Consumption.

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Kremer, Jonathan Isaak; Gömpel, Katharina; Bakuradze, Tamara; Eisenbrand, Gerhard; Richling, Elke

2018-04-01

Coffee is a major natural source of niacin in the human diet, as it is formed during coffee roasting from the alkaloid trigonelline. The intention of our study was to monitor the urinary excretion of niacin metabolites after coffee consumption under controlled diet. We performed a 4-day human intervention study on the excretion of major niacin metabolites in the urine of volunteers after ingestion of 500 mL regular coffee containing 34.8 μmol nicotinic acid (NA) and 0.58 μmol nicotinamide (NAM). In addition to NA and NAM, the metabolites N 1 -methylnicotinamide (NMNAM), N 1 -methyl-2-pyridone-5-carboxamide (2-Py), and nicotinuric acid (NUA) were identified and quantified in the collected urine samples by stable isotope dilution analysis (SIVA) using HPLC-ESI-MS/MS. Rapid urinary excretion was observed for the main metabolites (NA, NAM, NMNAM, and 2-Py), with t max values within the first hour after ingestion. NUA appeared in traces even more rapidly. In sum, 972 nmol h -1 of NA, NAM, NMNAM, and 2-Py were excreted within 12 h after coffee consumption, corresponding to 6% of the ingested NA and NAM. The results indicate regular coffee consumption to be a source of niacin in human diet. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High-affinity α4β2 nicotinic receptors mediate the impairing effects of acute nicotine on contextual fear extinction.

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Kutlu, Munir Gunes; Holliday, Erica; Gould, Thomas J

2016-02-01

Previously, studies from our lab have shown that while acute nicotine administered prior to training and testing enhances contextual fear conditioning, acute nicotine injections prior to extinction sessions impair extinction of contextual fear. Although there is also strong evidence showing that the acute nicotine's enhancing effects on contextual fear conditioning require high-affinity α4β2 nicotinic acetylcholine receptors (nAChRs), it is unknown which nAChR subtypes are involved in the acute nicotine-induced impairment of contextual fear extinction. In this study, we investigated the effects of acute nicotine administration on contextual fear extinction in knock-out (KO) mice lacking α4, β2 or α7 subtypes of nAChRs and their wild-type (WT) littermates. Both KO and WT mice were first trained and tested for contextual fear conditioning and received a daily contextual extinction session for 4 days. Subjects received intraperitoneal injections of nicotine (0.18 mg/kg) or saline 2-4 min prior to each extinction session. Our results showed that the mice that lack α4 and β2 subtypes of nAChRs showed normal contextual fear extinction but not the acute nicotine-induced impairment while the mice that lack the α7 subtype showed both normal contextual extinction and nicotine-induced impairment of contextual extinction. In addition, control experiments showed that acute nicotine-induced impairment of contextual fear extinction persisted when nicotine administration was ceased and repeated acute nicotine administrations alone did not induce freezing behavior in the absence of context-shock learning. These results clearly demonstrate that high-affinity α4β2 nAChRs are necessary for the effects of acute nicotine on contextual fear extinction. Copyright © 2015 Elsevier Inc. All rights reserved.

Correlations of Maternal Buprenorphine Dose, Buprenorphine, and Metabolite Concentrations in Meconium with Neonatal Outcomes

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Kacinko, SL; Jones, HE; Johnson, RE; Choo, RE; Huestis, MA

2009-01-01

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS ) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS. PMID:18701886

Renal transport and metabolism of nicotinic acid

International Nuclear Information System (INIS)

Schuette, S.; Rose, R.C.

1986-01-01

Renal metabolism and brush-border transport of nicotinic acid were studied in renal cortical slices and brush-border membrane vesicles exposed to a physiological concentration of vitamin (2.2-3.5 microM). Vesicle transport of [ 3 H]nicotinic acid was found to be Na+ dependent and concentrative. The presence of a Na+ gradient resulted in a fivefold increase in the rate of nicotinic acid uptake over that observed with mannitol and caused a transient nicotinic acid accumulation two- to fourfold above the equilibrium value. The effects of membrane potential, pH, and elimination of Na+-H+ exchange were also studied. Cortical slices and isolated tubules exposed to 2.2 microM [ 14 C]nicotinic acid took up vitamin and rapidly metabolized most of it to intermediates in the Preiss-Handler pathway for NAD biosynthesis; little free nicotinic acid was detectable intracellularly. The replacement of Na+ with Li+ in the bathing medium reduced total accumulation of 14 C label primarily as a result of reduced nicotinic acid uptake. Cortical tissue concentrated free nicotinic acid only when the involved metabolic pathways were saturated by levels of nicotinic acid far in excess of what occurs in vivo

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

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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; pe-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.

Nicotine, adolescence, and stress: A review of how stress can modulate the negative consequences of adolescent nicotine abuse.

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Holliday, Erica; Gould, Thomas J

2016-06-01

In order to continue the decline of smoking prevalence, it is imperative to identify factors that contribute to the development of nicotine and tobacco addiction, such as adolescent initiation of nicotine use, adolescent stress, and their interaction. This review highlights the biological differences between adolescent and adults in nicotine use and resulting effects, and examines the enduring consequences of adolescent nicotine administration. A review of both clinical and preclinical literature indicates that adolescent, but not adult, nicotine administration leads to increased susceptibility for development of long-lasting impairments in learning and affect. Finally, the role stress plays in normal adolescent development, the deleterious effects stress has on learning and memory, and the negative consequences resulting from the interaction of stress and nicotine during adolescence is reviewed. The review concludes with ways in which future policies could benefit by addressing adolescent stress as a means of reducing adolescent nicotine abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adolescents' understanding and use of nicotine in e-cigarettes.

Science.gov (United States)

Pepper, Jessica K; Farrelly, Matthew C; Watson, Kimberly A

2018-07-01

Nicotine harms adolescent brain development and contributes to addiction. Some adolescents report using nicotine-free e-cigarettes, but the accuracy of their reporting is unclear. We explored adolescents' use of nicotine-free e-cigarettes and understanding of chemicals in e-cigarettes, including nicotine. Using social media, we recruited 1589 US adolescents (aged 15-17) who reported past 30-day use of e-cigarettes in 2016. We assessed perceptions of the nicotine source in e-liquid and whether e-cigarette aerosol is just "water vapor." We explored differences among adolescents who usually used e-cigarettes with nicotine (n = 473) and without nicotine (n = 452). We used weights to calibrate our sample to the Youth Risk Behavior Survey. Twenty-nine percent usually used e-cigarettes without nicotine, 28% with nicotine, 39% with "both," and 5% were "not sure." Few participants (17% of non-nicotine users vs. 34% of nicotine users, p e-cigarette aerosol was just water vapor were more likely to usually use without nicotine. Older adolescents and current tobacco users were less likely to usually use without nicotine. The adolescents who reported usually using e-cigarettes without nicotine had poorer knowledge of e-cigarettes. This lack of understanding could contribute to inaccurate reporting of nicotine use. Most youth thought the nicotine in e-cigarettes was artificial, potentially indicating a belief that this nicotine is "safer." The US Food & Drug Administration will require nicotine warnings on e-cigarettes in 2018; a complementary educational campaign could address youths' misperceptions about nicotine and other chemicals in e-cigarette aerosol. Copyright © 2018 Elsevier Ltd. All rights reserved.

Vitamin E Nicotinate

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Kimbell R. Duncan

2017-03-01

Full Text Available Vitamin E refers to a family of compounds that function as lipid-soluble antioxidants capable of preventing lipid peroxidation. Naturally occurring forms of vitamin E include tocopherols and tocotrienols. Vitamin E in dietary supplements and fortified foods is often an esterified form of α-tocopherol, the most common esters being acetate and succinate. The vitamin E esters are hydrolyzed and converted into free α-tocopherol prior to absorption in the intestinal tract. Because its functions are relevant to many chronic diseases, vitamin E has been extensively studied in respect to a variety of diseases as well as cosmetic applications. The forms of vitamin E most studied are natural α-tocopherol and the esters α-tocopheryl acetate and α-tocopheryl succinate. A small number of studies include or focus on another ester form, α-tocopheryl nicotinate, an ester of vitamin E and niacin. Some of these studies raise the possibility of differences in metabolism and in efficacy between vitamin E nicotinate and other forms of vitamin E. Recently, through metabolomics studies, we identified that α-tocopheryl nicotinate occurs endogenously in the heart and that its level is dramatically decreased in heart failure, indicating the possible biological importance of this vitamin E ester. Since knowledge about vitamin E nicotinate is not readily available in the literature, the purpose of this review is to summarize and evaluate published reports, specifically with respect to α-tocopheryl nicotinate with an emphasis on the differences from natural α-tocopherol or α-tocopheryl acetate.

Effects of the nicotinic agonist varenicline, nicotinic antagonist r-bPiDI, and DAT inhibitor (R)-modafinil on co-use of ethanol and nicotine in female P rats.

Science.gov (United States)

Maggio, Sarah E; Saunders, Meredith A; Baxter, Thomas A; Nixon, Kimberly; Prendergast, Mark A; Zheng, Guangrong; Crooks, Peter; Dwoskin, Linda P; Slack, Rachel D; Newman, Amy H; Bell, Richard L; Bardo, Michael T

2018-05-01

Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use. Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs. 15%, two-bottle choice), (2) nicotine alone (0.03 mg/kg/infusion, active vs. inactive lever), and (3) concurrent access to both EtOH and nicotine. Using this model, we examined the effects of (1) varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist with high affinity for the α4β2* subtype; (2) r-bPiDI, a subtype-selective antagonist at α6β2* nAChRs; and (3) (R)-modafinil, an atypical inhibitor of the dopamine transporter (DAT). In phases 1 and 2, pharmacologically relevant intake of EtOH and nicotine was achieved. In the concurrent access phase (phase 3), EtOH consumption decreased while nicotine intake increased relative to phases 1 and 2. For drug pretreatments, in the EtOH access phase (phase 1), (R)-modafinil (100 mg/kg) decreased EtOH consumption, with no effect on water consumption. In the concurrent access phase, varenicline (3 mg/kg), r-bPiDI (20 mg/kg), and (R)-modafinil (100 mg/kg) decreased nicotine self-administration but did not alter EtOH consumption, water consumption, or inactive lever pressing. These results indicate that therapeutics which may be useful for smoking cessation via selective inhibition of α4β2* or α6β2* nAChRs, or DAT inhibition, may not be sufficient to treat EtOH and nicotine co-use.

Transgenerational Exposure to Environmental Tobacco Smoke

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Xavier Joya

2014-07-01

Full Text Available Traditionally, nicotine from second hand smoke (SHS, active or passive, has been considered the most prevalent substance of abuse used during pregnancy in industrialized countries. Exposure to environmental tobacco smoke (ETS is associated with a variety of health effects, including lung cancer and cardiovascular diseases. Tobacco is also a major burden to people who do not smoke. As developing individuals, newborns and children are particularly vulnerable to the negative effects of SHS. In particular, prenatal ETS has adverse consequences during the entire childhood causing an increased risk of abortion, low birth weight, prematurity and/or nicotine withdrawal syndrome. Over the last years, a decreasing trend in smoking habits during pregnancy has occurred, along with the implementation of laws requiring smoke free public and working places. The decrease in the incidence of prenatal tobacco exposure has usually been assessed using maternal questionnaires. In order to diminish bias in self-reporting, objective biomarkers have been developed to evaluate this exposure. The measurement of nicotine and its main metabolite, cotinine, in non-conventional matrices such as cord blood, breast milk, hair or meconium can be used as a non-invasive measurement of prenatal SMS in newborns. The aim of this review is to highlight the prevalence of ETS (prenatal and postnatal using biomarkers in non-conventional matrices before and after the implementation of smoke free policies and health effects related to this exposure during foetal and/or postnatal life.

Tying up Nicotine: New Selective Competitive Antagonist of the Neuronal Nicotinic Acetylcholine Receptors

DEFF Research Database (Denmark)

Petersen, Ida Nymann; Crestey, François; Jensen, Anders A

2015-01-01

Conformational restriction of the pyrrolidine nitrogen in nicotine by the introduction of an ethylene bridge provided a potent and selective antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors. Resolution by chiral SFC, pharmacological characterization of the two enantiomers...

Nicotine Contamination in Particulate Matter Sampling

Directory of Open Access Journals (Sweden)

Eric Garshick

2009-02-01

Full Text Available We have addressed potential contamination of PM2.5 filter samples by nicotine from cigarette smoke. We collected two nicotine samples – one nicotine sampling filter was placed in-line after the collection of PM2.5 and the other stood alone. The overall correlation between the two nicotine filter levels was 0.99. The nicotine collected on the “stand-alone” filter was slightly greater than that on the “in-line” filter (mean difference = 1.10 μg/m3, but the difference was statistically significant only when PM2.5 was low (≤ 50 μg/m3. It is therefore important to account for personal and secondhand smoke exposure while assessing occupational and environmental PM.

Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders.

Science.gov (United States)

Kang, Dae-Wook; Ilhan, Zehra Esra; Isern, Nancy G; Hoyt, David W; Howsmon, Daniel P; Shaffer, Michael; Lozupone, Catherine A; Hahn, Juergen; Adams, James B; Krajmalnik-Brown, Rosa

2018-02-01

Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using 1 H-NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of phylotypes most closely related to Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further

Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders

Energy Technology Data Exchange (ETDEWEB)

Kang, Dae-Wook; Ilhan, Zehra Esra; Isern, Nancy G.; Hoyt, David W.; Howsmon, Daniel P.; Shaffer, Michael; Lozupone, Catherine A.; Hahn, Juergen; Adams, James B.; Krajmalnik-Brown, Rosa

2018-02-01

Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites- caprate, nicotinate, glutamine, thymine, and aspartate- may potentially function as a biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts.

Fetal Nicotine Exposure Increases Preference for Nicotine Odor in Early Postnatal and Adolescent, but Not Adult, Rats

Science.gov (United States)

Mantella, Nicole M.; Kent, Paul F.; Youngentob, Steven L.

2013-01-01

Human studies demonstrate a four-fold increased possibility of smoking in the children of mothers who smoked during pregnancy. Nicotine is the active addictive component in tobacco-related products, crossing the placenta and contaminating the amniotic fluid. It is known that chemosensory experience in the womb can influence postnatal odor-guided preference behaviors for an exposure stimulus. By means of behavioral and neurophysiologic approaches, we examined whether fetal nicotine exposure, using mini-osmotic pumps, altered the response to nicotine odor in early postnatal (P17), adolescent (P35) and adult (P90) progeny. Compared with controls, fetal exposed rats displayed an altered innate response to nicotine odor that was evident at P17, declined in magnitude by P35 and was absent at P90 - these effects were specific to nicotine odor. The behavioral effect in P17 rats occurred in conjunction with a tuned olfactory mucosal response to nicotine odor along with an untoward consequence on the epithelial response to other stimuli – these P17 neural effects were absent in P35 and P90 animals. The absence of an altered neural effect at P35 suggests that central mechanisms, such as nicotine-induced modifications of the olfactory bulb, bring about the altered behavioral response to nicotine odor. Together, these findings provide insights into how fetal nicotine exposure influences the behavioral preference and responsiveness to the drug later in life. Moreover, they add to a growing literature demonstrating chemosensory mechanisms by which patterns of maternal drug use can be conveyed to offspring, thereby enhancing postnatal vulnerability for subsequent use and abuse. PMID:24358374

Effect of a nicotine vaccine on nicotine binding to the beta2-nAChRs in vivo in human tobacco smokers

Science.gov (United States)

Esterlis, Irina; Hannestad, Jonas O.; Perkins, Evgenia; Bois, Frederic; D’Souza, D. Cyril; Tyndale, Rachel F.; Seibyl, John P.; Hatsukami, Dorothy M.; Cosgrove, Kelly P.; O’Malley, Stephanie S.

2013-01-01

Objective Nicotine acts in the brain to promote smoking in part by binding to the beta2-containing nicotinic acetylcholine receptors (β2*-nAChRs) and acting in the mesolimbic reward pathway. The effects of nicotine from smoking one tobacco cigarette are significant (80% of β2*-nAChRs occupied for >6h). This likely contributes to the maintenance of smoking dependence and low cessation outcomes. Development of nicotine vaccines provides potential for alternative treatments. We used [123I]5IA-85380 SPECT to evaluate the effect of 3′-AmNic-rEPA on the amount of nicotine that binds to the β2*-nAChRs in the cortical and subcortical regions in smokers. Method Eleven smokers (36years (SD=13); 19cig/day (SD=11) for 10years (SD=7) who were dependent on nicotine (Fagerström Test of Nicotine Dependence score =5.5 (SD=3); plasma nicotine 9.1 ng/mL (SD=5)) participated in 2 SPECT scan days: before and after immunization with 4–400μg doses of 3′-AmNic-rEPA. On SPECT scan days, 3 30-min baseline emission scans were obtained, followed by administration of IV nicotine (1.5mg/70kg) and up to 9 30-min emission scans. Results β2*-nAChR availability was quantified as VT/fP and nicotine binding was derived using the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding (F=5.19, df=1,10, p=0.05). Significant positive correlations were observed between nicotine bound to β2*-nAChRs and nicotine injected before but not after vaccination (p=0.05 vs. p=0.98). There was a significant reduction in the daily number of cigarettes and desire for a cigarette (p=.01 and p=.04, respectively). Conclusions This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to β2*-nAChRs and disrupt the relationship between nicotine administered vs. nicotine available to occupy β2*-nAChRs. PMID:23429725

Effects of a selective cannabinoid CB2 agonist and antagonist on intravenous nicotine self administration and reinstatement of nicotine seeking.

Directory of Open Access Journals (Sweden)

Islam Gamaleddin

Full Text Available Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2 have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg and CB2 agonist AM1241 (1 to 10 mg/kg on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior.

In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.

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Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P; Lichtman, Aron H; Carroll, F Ivy; Greenwald, Mark; Miles, Michael F; Damaj, M Imad

2017-05-15

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nicotine transport in lung and non-lung epithelial cells.

Science.gov (United States)

Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

2017-11-01

Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of nicotine in the neonatal quinpirole rodent model of psychosis: Neural plasticity mechanisms and nicotinic receptor changes.

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Peterson, Daniel J; Gill, W Drew; Dose, John M; Hoover, Donald B; Pauly, James R; Cummins, Elizabeth D; Burgess, Katherine C; Brown, Russell W

2017-05-15

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal's lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1mg/kg) or saline from postnatal days (P)1-21. Animals were given ip injections of either saline or nicotine (0.5mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not α7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking. Copyright © 2017. Published by Elsevier B.V.

Compound list: nicotinic acid [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available nicotinic acid NIC 00081 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hum...an/in_vitro/nicotinic_acid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/R...at/in_vitro/nicotinic_acid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vivo/Liver/Single/nicotinic_acid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc

Discriminating nicotine and non-nicotine containing e-liquids using infrared spectroscopy.

Science.gov (United States)

Deconinck, E; Bothy, J L; Barhdadi, S; Courselle, P

2016-02-20

In a few countries, including Belgium, nicotine-containing e-cigarettes and e-liquids are considered medicines, and therefore cannot freely be sold, but should be distributed in a pharmacy. The fact that in the neighbouring countries these products are freely available, poses a problem for custom personnel, the more the nicotine content of the products is not always labelled, especially when they are bought through internet. Therefore there is a need for easy-to-use equipment and methods to perform a first on site screening of intercepted samples, both for border control as to check label compliance of the sample. The use of attenuated total reflectance-infrared spectroscopy (ATR-IR) and near infrared spectroscopy (NIR), combined with chemometrics was evaluated for the discrimination between nicotine containing and non-nicotine containing samples. It could be concluded that both ATR-IR and NIR could be used for the discrimination when combined with the appropriate chemometric techniques. The presented techniques do not need sample preparation and result in models with a minimum of false negative samples. If a large enough training set can be established the interpretation can be fully automated, making the presented approach suitable for on-site screening of e-liquid samples. Copyright © 2015 Elsevier B.V. All rights reserved.

In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT

International Nuclear Information System (INIS)

Kassiou, Michael; Eberl, Stefan; Meikle, Steven R.; Birrell, Alex; Constable, Chris; Fulham, Michael J.; Wong, Dean F.; Musachio, John L.

2001-01-01

To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[ 123 I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[ 123 I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V d ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V d was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V d or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment

In vivo human buccal permeability of nicotine

DEFF Research Database (Denmark)

Adrian, Charlotte L; Olin, Helle B D; Dalhoff, Kim

2006-01-01

The aim was to examine the in vivo buccal pH-dependent permeability of nicotine in humans and furthermore compare the in vivo permeability of nicotine to previous in vitro permeability data. The buccal permeability of nicotine was examined in a three-way cross-over study in eight healthy non......-smokers using a buccal perfusion cell. The disappearance of nicotine from perfusion solutions with pH 6.0, 7.4, and 8.1 was studied for 3h. The apparent permeability of nicotine (P(app)) was determined at each pH value. Parotid saliva was collected in an attempt to assess systemic levels of nicotine....... The disappearance rate of nicotine increased significantly as the pH increased, which resulted in P(app) values of 0.57+/-0.55 x 10(-4), 2.10+/-0.23 x 10(-4), and 3.96+/-0.54 x 10(-4)cms(-1) (mean+/-S.D.) at pH 6.0, 7.4, and 8.1, respectively. A linear relationship (R(2)=0.993) was obtained between the P...

Bioelectronic sniffer for nicotine using enzyme inhibition.

Science.gov (United States)

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).

Nicotine adsorption on single wall carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Girao, Eduardo C. [Departamento de Fisica, Universidade Federal do Ceara, Caixa Postal 6030, Campus do Pici, 60455-900 Fortaleza, Ceara (Brazil); Fagan, Solange B.; Zanella, Ivana [Area de Ciencias Tecnologicas, Centro Universitario Franciscano - UNIFRA, 97010-032 Santa Maria, RS (Brazil); Filho, Antonio G. Souza, E-mail: agsf@fisica.ufc.br [Departamento de Fisica, Universidade Federal do Ceara, Caixa Postal 6030, Campus do Pici, 60455-900 Fortaleza, Ceara (Brazil)

2010-12-15

This work reports a theoretical study of nicotine molecules interacting with single wall carbon nanotubes (SWCNTs) through ab initio calculations within the framework of density functional theory (DFT). Different adsorption sites for nicotine on the surface of pristine and defective (8,0) SWCNTs were analyzed and the total energy curves, as a function of molecular position relative to the SWCNT surface, were evaluated. The nicotine adsorption process is found to be energetically favorable and the molecule-nanotube interaction is intermediated by the tri-coordinated nitrogen atom from the nicotine. It is also predicted the possibility of a chemical bonding between nicotine and SWCNT through the di-coordinated nitrogen.

Effects of Electronic Cigarette Liquid Nicotine Concentration on Plasma Nicotine and Puff Topography in Tobacco Cigarette Smokers: A Preliminary Report.

Science.gov (United States)

Lopez, Alexa A; Hiler, Marzena M; Soule, Eric K; Ramôa, Carolina P; Karaoghlanian, Nareg V; Lipato, Thokozeni; Breland, Alison B; Shihadeh, Alan L; Eissenberg, Thomas

2016-05-01

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 study examined the extent to which ECIG liquid nicotine concentration is related to user plasma nicotine concentration in ECIG-naïve tobacco cigarette smokers. Sixteen ECIG-naïve cigarette smokers completed four laboratory sessions that differed by the nicotine concentration of the liquid (0, 8, 18, or 36 mg/ml) that was placed into a 1.5 Ohm, dual coil "cartomizer" powered by a 3.3V battery. In each session, participants completed two, 10-puff ECIG use bouts with a 30-second inter-puff interval; bouts were separated by 60 minutes. Venous blood was sampled before and after bouts for later analysis of plasma nicotine concentration; puff duration, volume, and average flow rate were measured during each bout. In bout 1, relative to the 0mg/ml nicotine condition (mean = 3.8 ng/ml, SD = 3.3), plasma nicotine concentration increased significantly immediately after the bout for the 8 (mean = 8.8 ng/ml, SD = 6.3), 18 (mean = 13.2 ng/ml, SD = 13.2), and 36 mg/ml (mean = 17.0 ng/ml, SD = 17.9) liquid concentration. A similar pattern was observed after bout 2. Average puff duration in the 36 mg/ml condition was significantly shorter compared to the 0mg/ml nicotine condition. Puff volume increased during the second bout for 8 and 18 mg/ml conditions. For a given ECIG device, nicotine delivery may be directly related to liquid concentration. ECIG-naïve cigarette smokers can, from their first use bout, attain cigarette-like nicotine delivery profiles with some currently available ECIG products. Liquid nicotine concentration can influence plasma nicotine concentration in ECIG-naïve cigarette smokers, and, at some concentrations, the nicotine delivery profile of a 3.3V ECIG with a dual coil, 1.5-Ohm cartomizer approaches that of a combustible tobacco cigarette in this

Stable isotope studies of nicotine kinetics and bioavailability

International Nuclear Information System (INIS)

Benowitz, N.L.; Jacob, P. III; Denaro, C.; Jenkins, R.

1991-01-01

The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine

Characterization and Genome Analysis of a Nicotine and Nicotinic Acid-Degrading Strain Pseudomonas putida JQ581 Isolated from Marine.

Science.gov (United States)

Li, Aiwen; Qiu, Jiguo; Chen, Dongzhi; Ye, Jiexu; Wang, Yuhong; Tong, Lu; Jiang, Jiandong; Chen, Jianmeng

2017-05-31

The presence of nicotine and nicotinic acid (NA) in the marine environment has caused great harm to human health and the natural environment. Therefore, there is an urgent need to use efficient and economical methods to remove such pollutants from the environment. In this study, a nicotine and NA-degrading bacterium-strain JQ581-was isolated from sediment from the East China Sea and identified as a member of Pseudomonas putida based on morphology, physio-biochemical characteristics, and 16S rDNA gene analysis. The relationship between growth and nicotine/NA degradation suggested that strain JQ581 was a good candidate for applications in the bioaugmentation treatment of nicotine/NA contamination. The degradation intermediates of nicotine are pseudooxynicotine (PN) and 3-succinoyl-pyridine (SP) based on UV, high performance liquid chromatography, and liquid chromatography-mass spectrometry analyses. However, 6-hydroxy-3-succinoyl-pyridine (HSP) was not detected. NA degradation intermediates were identified as 6-hydroxynicotinic acid (6HNA). The whole genome of strain JQ581 was sequenced and analyzed. Genome sequence analysis revealed that strain JQ581 contained the gene clusters for nicotine and NA degradation. This is the first report where a marine-derived Pseudomonas strain had the ability to degrade nicotine and NA simultaneously.

Inside-out neuropharmacology of nicotinic drugs.

Science.gov (United States)

Henderson, Brandon J; Lester, Henry A

2015-09-01

Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as "inside-out pharmacology". This term contrasts with the better-known, acute, "outside-in" effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tolerance to and cross tolerance between ethanol and nicotine.

Science.gov (United States)

Collins, A C; Burch, J B; de Fiebre, C M; Marks, M J

1988-02-01

Female DBA mice were subjected to one of four treatments: ethanol-containing or control diets, nicotine (0.2, 1.0, 5.0 mg/kg/hr) infusion or saline infusion. After removal from the liquid diets or cessation of infusion, the animals were challenged with an acute dose of ethanol or nicotine. Chronic ethanol-fed mice were tolerant to the effects of ethanol on body temperature and open field activity and were cross tolerant to the effects of nicotine on body temperature and heart rate. Nicotine infused animals were tolerant to the effects of nicotine on body temperature and rotarod performance and were cross tolerant to the effects of ethanol on body temperature. Ethanol-induced sleep time was decreased in chronic ethanol- but not chronic nicotine-treated mice. Chronic drug treatment did not alter the elimination rate of either drug. Chronic ethanol treatment did not alter the number or affinity of brain nicotinic receptors whereas chronic nicotine treatment elicited an increase in the number of [3H]-nicotine binding sites. Tolerance and cross tolerance between ethanol and nicotine is discussed in terms of potential effects on desensitization of brain nicotinic receptors.

Transdermal nicotine absorption handling e-cigarette refill liquids.

Science.gov (United States)

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.

A Case of Acute Eosinophilic Pneumonia Following Short-Term Passive Smoking: An Evidence of Very High Level of Urinary Cotinine

Directory of Open Access Journals (Sweden)

Kosaku Komiya

2010-01-01

The level of urinary cotinine, which is a biomarker of smoke exposure, was considerably higher (0.198 μg/ml [201 ng/mg Creatinine] than that in nonsmokers, but never detected following period. This case suggests that short-term passive smoking may cause AEP.

Urinary cotinine and breath carbon monoxide levels among bar and restaurant employees in ankara.

Science.gov (United States)

Caman, Ozge Karadag; Erguder, Berrin I; Ozcebe, Hilal; Bilir, Nazmi

2013-08-01

Hospitality sector employees constitute one of the key groups with respect to their secondhand tobacco smoke exposure at work. This study aimed to detect urinary cotinine and breath carbon monoxide (CO) levels among bar and restaurant employees in Ankara, as well as the employees' opinions on the new antitobacco law, changes in smoking behavior, and subjective health status before and after the law entered into force. This before-after study was conducted in 19 premises, with the participation of 65 employees before implementation and 81 employees 3 months after implementation of the new antitobacco law in the hospitality sector. Data in both phases were collected through face-to-face surveys, breath CO measurements, and urinary cotinine analysis. Descriptive statistics were used to summarize data, whereas chi-square test, paired and unpaired t tests, and analysis of variance were used to compare groups. Most of the restaurant and bar employees were male and below 35 years old. Before-after comparison showed that health complaints of the hospitality sector employees such as watering and itching in the eyes, difficulty in breathing, and cough (p law. Among the smoking employees, mean number of cigarettes smoked was also found to decrease (p = .012). Majority of the employees (83.8%) were found to support the smoking ban in enclosed public places. Results of this study provide solid evidence on the positive health effects of smoke-free laws and employees' support for smoke-free workplaces.

REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

Science.gov (United States)

Perkins, Kenneth A.; Karelitz, Joshua L.; Michael, Valerie C.

2015-01-01

Background Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. Methods We assessed acute effects of nicotine via electronic cigarettes (“e-cigarettes”) on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10 ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled “36 mg/ml”) or placebo (“0”) e-cigarette, or no e-cigarette use. A fourth session involved smoking one’s own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Results Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Conclusions Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. PMID:26070455

Reinforcement enhancing effects of acute nicotine via electronic cigarettes.

Science.gov (United States)

Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C

2015-08-01

Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. We assessed acute effects of nicotine via electronic cigarettes ("e-cigarettes") on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled "36mg/ml") or placebo ("0″) e-cigarette, or no e-cigarette use. A fourth session involved smoking one's own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Children's exposure to passive smoking in England since the 1980s: cotinine evidence from population surveys

Science.gov (United States)

Jarvis, Martin J; Goddard, Eileen; Higgins, Vanessa; Feyerabend, Colin; Bryant, Andrew; Cook, Derek G

2000-01-01

Objective To determine whether children's exposure to passive smoking has changed since the late 1980s. Design Cross sectional surveys of nationally representative samples of secondary school children carried out between 1988 and 1998 by Office for National Statistics. Setting England. Subjects Secondary school children aged 11-15. Main outcome measures Salivary cotinine concentrations in non-smoking children. Results Cotinine concentrations in all non-smoking children almost halved between 1988 and 1998, from a geometric mean of 0.96 (95% confidence interval 0.83 to 1.11) ng/ml in 1988 to 0.52 (0.43 to 0.62) ng/ml in 1998. This reduction was largely due to reductions in exposure in children from non-smoking households and to decreases in the percentage of parents who smoked. Children living with mothers or fathers who smoked experienced little reduction in exposure. Conclusions Exposure to passive smoking among children in England has approximately halved since the late 1980s. This reduction is partly explained by the fall in the percentage of both mothers and fathers who smoke and is also likely to reflect reductions of smoking in public places. However, there is only limited evidence that children from smoking households have experienced a reduction in exposure through parents' avoidance of smoking in their presence. PMID:10926591

Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability.

Science.gov (United States)

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

2017-11-01

Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.

Opioid Analgesics and Nicotine: More Than Blowing Smoke.

Science.gov (United States)

Yoon, Jin H; Lane, Scott D; Weaver, Michael F

2015-09-01

Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

Nicotine pharmacokinetics and its application to intake from smoking.

Science.gov (United States)

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

NICOTINE EFFECTS ON THE ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

Science.gov (United States)

Considerable research has shown long-lasting effects of early exposure in experimental animals to nicotine. Anatoxin-a is produced by cyanobacteria and has been shown to be a potent nicotinic agonist. This experiment evaluated the motor activity of adult mice, and their respons...

Effect of nicotine on negative affect among more impulsive smokers.

Science.gov (United States)

Doran, Neal; McChargue, Dennis; Spring, Bonnie; VanderVeen, Joe; Cook, Jessica Werth; Richmond, Malia

2006-08-01

In the present study, the authors tested the hypothesis that nicotine would provide greater relief from negative affect for more impulsive smokers than for less impulsive smokers. Euthymic adult smokers (N=70) participated in 2 laboratory sessions, during which they underwent a negative mood induction (music + autobiographical memory), then smoked either a nicotinized or de-nicotinized cigarette. Mixed-effects regression yielded a significant Impulsivity x Condition (nicotinized vs. de-nicotinized) x Time interaction. Simple effects analyses showed that heightened impulsivity predicted greater negative affect relief after smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette. These data suggest that nicotine may be a disproportionately powerful negative reinforcer for highly impulsive smokers, promoting higher levels of nicotine dependence and inhibiting smoking cessation.

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

Science.gov (United States)

Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin

International Nuclear Information System (INIS)

Clarke, P.B.; Schwartz, R.D.; Paul, S.M.; Pert, C.B.; Pert, A.

1985-01-01

Three radioligands have been commonly used to label putative nicotinic cholinoceptors in the mammalian central nervous system: the agonists [ 3 H]nicotine and [ 3 H]acetylcholine ([ 3 H]ACh--in the presence of atropine to block muscarinic receptors), and the snake venom extract, [ 125 I]-alpha-bungarotoxin([ 125 I]BTX), which acts as a nicotinic antagonist at the neuromuscular junction. Binding studies employing brain homogenates indicate that the regional distributions of both [ 3 H]nicotine and [ 3 H]ACh differ from that of [ 125 I]BTX. The possible relationship between brain sites bound by [ 3 H]nicotine and [ 3 H]ACh has not been examined directly. The authors have used the technique of autoradiography to produce detailed maps of [ 3 H]nicotine, [ 3 H]ACh, and [ 125 I]BTX labeling; near-adjacent tissue sections were compared at many levels of the rat brain. The maps of high affinity agonist labeling are strikingly concordant, with highest densities in the interpeduncular nucleus, most thalamic nuclei, superior colliculus, medial habenula, presubiculum, cerebral cortex (layers I and III/IV), and the substantia nigra pars compacta/ventral tegmental area. The pattern of [ 125 I]BTX binding is strikingly different, the only notable overlap with agonist binding being the cerebral cortex (layer I) and superior colliculus. [ 125 I]BTX binding is also dense in the inferior colliculus, cerebral cortex (layer VI), hypothalamus, and hippocampus, but is virtually absent in thalamus. Various lines of evidence suggest that the high affinity agonist-binding sites in brain correspond to nicotinic cholinergic receptors similar to those found at autonomic ganglia; BTX-binding sites may also serve as receptors for nicotine and are possibly related to neuromuscular nicotinic cholinoceptors

Nicotine Reduction Revisited: Science and Future Directions

Science.gov (United States)

Hatsukami, Dorothy K.; Perkins, Kenneth A.; LeSage, Mark G.; Ashley, David L.; Henningfield, Jack E.; Benowitz, Neal L.; Backinger, Cathy; Zeller, Mitch

2015-01-01

Regulation of nicotine levels in cigarettes and other tobacco products is now possible with the passage of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) in 2009 giving the U.S. Food and Drug Administration authority to regulate tobacco products, and with Articles 9-11 of the World Health Organization Framework Convention on Tobacco Control.[1-2] Both regulatory approaches allow establishing product standards for tobacco constituents, including nicotine. The FSPTCA does not allow nicotine levels to be decreased to zero, although FDA has the authority to reduce nicotine yields to very low, presumably non-addicting levels. The proposal to reduce levels of nicotine to a level that is non-addicting was originally suggested in 1994.[3] Reduction of nicotine in tobacco products could potentially have a profound impact on reducing tobacco-related morbidity and mortality. To examine this issue, two meetings were convened in the United States with non-tobacco-industry scientists of varied disciplines, tobacco control policy-makers and representatives of government agencies. This article provides an overview of the current science in the area of reduced nicotine content cigarettes and key conclusions and recommendations for research and policy that emerged from the deliberations of the meeting members. PMID:20876072

Nicotine and endogenous opioids: neurochemical and pharmacological evidence.

Science.gov (United States)

Hadjiconstantinou, Maria; Neff, Norton H

2011-06-01

Although the mesolimbic dopamine hypothesis is the most influential theory of nicotine reward and reinforcement, there has been a consensus that other neurotransmitter systems contribute to the addictive properties of nicotine as well. In this regard, the brain opioidergic system is of interest. Striatum is rich in opioid peptides and opioid receptors, and striatal opioidergic neurons are engaged in a bidirectional communication with midbrain dopaminergic neurons, closely regulating each other's activity. Enkephalins and dynorphins exert opposing actions on dopaminergic neurons, increasing and decreasing dopamine release respectively, and are components of circuits promoting positive or negative motivational and affective states. Moreover, dopamine controls the synthesis of striatal enkephalins and dynorphins. Evidence suggests that opioidergic function is altered after nicotine and endogenous opioids are involved in nicotine's behavioral effects. 1) The synthesis and release of β-endorphin, met-enkephalin and dynorphin in brain, especially nucleus accumbens (NAc), are altered after acute or chronic nicotine treatment and during nicotine withdrawal. 2) Although opioid receptor binding and mRNA do not appear to change in the striatum during nicotine withdrawal, the activity of κ-opioid (KOPr) and δ-opioid (DOPr) receptors is attenuated in NAc. 3) The nicotine withdrawal syndrome reminisces that of opiates, and naloxone precipitates some of its somatic, motivational, and affective signs. 4) Genetic and pharmacological studies indicate that μ-opioid (MOPr) receptors are mainly involved in nicotine reward, while DOPrs contribute to the emotional and KOPrs to the aversive responses of nicotine. 5) Finally, MOPrs and enkephalin, but not β-endorphin or dynorphin, are necessary for the physical manifestations of nicotine withdrawal. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. Copyright © 2010 Elsevier

Nicotine Analysis in Several Non-Tobacco Plant Materials

Directory of Open Access Journals (Sweden)

Moldoveanu Serban C.

2016-04-01

Full Text Available Present study describes the determination of nicotine in various plant samples with a low content of this compound. Nicotine is found naturally in plants from the Solanaceae family. The plants from Nicotiana genus contain large levels of nicotine. However, only low levels are present in plants from Solanum genus including potato, tomato, eggplant, and from Capsicum genus, which are used as food. Because the levels of nicotine in these materials are in the range of parts per billion, the measurements are difficult and the results are very different from study to study. The present study evaluated the level of nicotine in a number of plants (fruits, roots, leaves, tubers from Solanaceae family (not including Nicotiana genus and from several other vegetables commonly used as food. The analysis consisted of the treatment of plant material with an aqueous solution 5% NaOH at 70°C for 30 min, followed by extraction with TBME containing d3-nicotine as an internal standard. The TBME organic layer was analyzed on a 7890B/7000C GC-MS/MS system with a 30 m × 0.25 mm, 0.25 μm film CAM column. The MS/MS system worked in MRM positive ionization mode monitoring the transition 162 - 84 for nicotine and 165 - 87 for d3-nicotine. Particular attention was given to the preservation of the intact levels of nicotine in the plant material. The plant material was analyzed as is, without drying and with minimal exposure to contaminations. Separately, the moisture of the plant material was measured in order to report the nicotine level on a dry-basis. Levels of nicotine around 180 ng/g dry material were obtained for tomatoes and eggplant (fruit and lower levels were obtained for green pepper and potato. Similar levels to that in the tomato fruit were detected in tomato leaves. Materials from other plant families also showed traces of nicotine. [Beitr. Tabakforsch. Int. 27 (2016 54-59

Nicotine-selective radiation-induced poly(acrylamide/maleic acid) hydrogels

International Nuclear Information System (INIS)

Saraydin, D.; Karadag, E.; Caldiran, Y.; Gueven, O.

2001-01-01

Nicotine-selective poly(acrylamide/maleic acid) (AAm/MA) hydrogels prepared by γ-irradiation were used in experiments on swelling, diffusion, and interactions of the pharmaceuticals nicotine, nicotinic acid, nicotinamide, and nikethamide. For AAm/MA hydrogel containing 60 mg maleic acid and irradiated at 5.2 kGy, the studies indicated that swelling increased in the following order; nicotine>nicotinamide>nikethamide>nicotinic acid>water. Diffusions of water and the pharmaceuticals within the hydrogels were found to be non-Fickian in character. AAm/MA hydrogel sorbed only nicotine and did not sorb nicotinamide, nikethamide and nicotinic acid in the binding experiments. S-type adsorption in Giles's classification system was observed. Some binding and thermodynamic parameters for AAm/MA hydrogel-nicotine system were calculated using the Scatchard method. The values of adsorption heat and free energy of this system were found to be negative whereas adsorption entropy was found to be positive. (author)

Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

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Suarez, S.V.; Changeux, J.P.; Granon, S. [Unite de Neurobiologie Integrative du Systeme Cholinergique, URA CNRS 2182, Institut Pasteur, Departement de Neuroscience, 25 rue du Dr Roux, 75015 Paris (France); Amadon, A.; Giacomini, E.; Le Bihan, D. [Service Hospitalier Frederic Joliot, 4 place du general Leclerc, 91400 Orsay (France); Wiklund, A. [Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm (Sweden)

2009-07-01

Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity {beta}2-containing nicotinic receptors ({beta}2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the {beta}2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and {beta}2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, {beta}2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via {alpha}7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on {beta}2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

International Nuclear Information System (INIS)

Suarez, S.V.; Changeux, J.P.; Granon, S.; Amadon, A.; Giacomini, E.; Le Bihan, D.; Wiklund, A.

2009-01-01

Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity β2-containing nicotinic receptors (β2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the β2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and β2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, β2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via α7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on β2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors.

NARCIS (Netherlands)

de Kloet, S.F.; Mansvelder, H.D.; de Vries, T.J.

2015-01-01

Nicotine addiction is highly prevalent in current society and is often comorbid with other diseases. In the central nervous system, nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs) and its effects depend on location and receptor composition. Although nicotinic receptors are

Exposure to Secondhand Smoke Among Nonsmokers in New York City in the Context of Recent Tobacco Control Policies: Current Status, Changes Over the Past Decade, and National Comparisons.

Science.gov (United States)

Perlman, Sharon E; Chernov, Claudia; Farley, Shannon M; Greene, Carolyn M; Aldous, Kenneth M; Freeman, Amy; Rodriguez-Lopez, Jesica; Thorpe, Lorna E

2016-11-01

Exposure to secondhand smoke is hazardous and can cause cancer, coronary heart disease, and birth defects. New York City (NYC) and other jurisdictions have established smoke-free air laws in the past 10-15 years. NYC Health and Nutrition Examination Survey (HANES) 2013-2014 was a population-based survey of NYC residents, aged 20 years and older, in which biospecimens were collected and cotinine levels were measured. Secondhand smoke exposure was assessed by demographics and risk factors and compared with that from NYC HANES 2004 and national HANES. More than a third (37.1%, 95% confidence interval [CI] = 33.3%-41.2%) of nonsmoking adult New Yorkers were exposed to secondhand smoke, defined as a cotinine level of 0.05-10ng/mL. This was significantly lower than in 2004 NYC HANES, when 56.7% (95% CI = 53.6%-59.7%) of nonsmokers were exposed to secondhand smoke, but was greater than the proportion of adults exposed nationwide, as measured by national HANES (24.4%, 95% CI = 22.0%-26.9% in 2011-2012). Men, non-Hispanic blacks, adults aged 20-39, those with less education, and those living in high-poverty neighborhoods were more likely to be exposed. There has been a large decrease in secondhand smoke exposure in NYC, although disparities persist. The decrease may be the result of successful policies to limit exposure to secondhand smoke in public places and of smokers smoking fewer cigarettes per day. Yet NYC residents still experience more secondhand smoke exposure than US residents overall. Possible explanations include multiunit housing, greater population density, and pedestrian exposure. Measuring exposure to secondhand smoke can be difficult, and few studies have monitored changes over time. This study uses serum cotinine, a nicotine metabolite, from a local population-based examination survey, the NYC HANES 2013-2014, to examine exposure to secondhand smoke in an urban area that has implemented stringent antismoking laws. Comparison with NYC HANES conducted 10

Nicotine increases brain functional network efficiency.

Science.gov (United States)

Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R

2012-10-15

Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. Published by Elsevier Inc.

What Are Tobacco, Nicotine, and E-Cigarette Products?

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... Drug Facts / Tobacco, Nicotine, & E-Cigarettes Tobacco, Nicotine, & E-Cigarettes Street names: Chew, Dip, Snuff Print Expand All Revised July 2017 What are tobacco, nicotine, and e-cigarette products? ©Shutterstock/ CatherineL-Prod Also known as: Cigarettes: ...

Counterfeit Electronic Cigarette Products with Mislabeled Nicotine Concentrations.

Science.gov (United States)

Omaiye, Esther E; Cordova, Iliana; Davis, Barbara; Talbot, Prue

2017-07-01

We compared nicotine concentrations in one brand of refill fluids that were purchased in 4 countries and labeled 0 mg of nicotine/mL. We then identified counterfeit e-cigarette products from these countries. Overall, 125 e-cigarette refill fluids were purchased in Nigeria, the United States (US), England, and China. Nicotine concentrations were measured using high performance liquid chromatography and compared to labeled concentrations. Refill fluids were examined to identify physical differences and grouped into authentic and counterfeit products. Whereas nicotine was in 51.7% (15/29) of the Nigerian, 3.7% (1/27) of the Chinese and 1.6% (1/61) of the American refill fluids (range = 0.4 - 20.4 mg/mL), 8 British products did not contain nicotine. Products from China, the US, and Nigeria with trace amounts of nicotine (0.4 to 0.6 mg/mL) were authentic; however, all products from Nigeria with more than 3.7 mg/mL were counterfeit. We introduce 2 novel issues in the e-cigarette industry, the production of counterfeit refill fluids under a brandjacked label and inclusion of nicotine in 81.3% of the counterfeit products labeled 0 mg/mL. This study emphasizes the need for better control and monitoring of nicotine containing products and sales outlets.

α-4 subunit of nicotinic acetylcholine receptor polymorphisms exhibit ...

African Journals Online (AJOL)

Background: Smoking behavior is influenced by both genetic and environmental factors. Nicotine is the major addictive substance in cigarettes. Nicotinic acetylcholine receptors (nAChRs) are thought to play an important role in nicotine addiction of smokers. One of the genes, α-4 subunit of nicotinic acetylcholine receptor ...

Antifungal activity of nicotine and its cadmium complex

International Nuclear Information System (INIS)

Zaidi, I.M.; Gul, A.

2005-01-01

Nicotine and its metal complex; Cd(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activities against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cadmium(II) iodide was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine is quite effective against the rare pathogenic and Non pathogenic fungi but comparatively less effective against Pathogenic fungi. Nicotine was found to be completely ineffective against the selected species of Occasional pathogenic fungi. Cadmium(II) iodide effectively inhibited Pathogenic and Non pathogenic fungi whereas relatively ineffective against the Occasional pathogenic and Rare pathogenic fungi. On the other hand, Cadmium(II) nicotine complex inhibited all the selected species of fungi except Fusarium solani. (author)

Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability

Science.gov (United States)

Fowler, Christie D.; Kenny, Paul J.

2013-01-01

Nicotine stimulates brain reward circuitries, most prominently the mesocorticolimbic dopamine system, and this action is considered critical in establishing and maintaining the tobacco smoking habit. Compounds that attenuate nicotine reward are considered promising therapeutic candidates for tobacco dependence, but many of these agents have other actions that limit their potential utility. Nicotine is also highly noxious, particularly at higher doses, and aversive reactions to nicotine after initial exposure can decrease the likelihood of developing a tobacco habit in many first time smokers. Nevertheless, relatively little is known about the mechanisms of nicotine aversion. The purpose of this review is to present recent new insights into the neurobiological mechanisms that regulate avoidance of nicotine. First, the role of the mesocorticolimbic system, so often associated with nicotine reward, in regulating nicotine aversion is highlighted. Second, genetic variation that modifies noxious responses to nicotine and thereby influences vulnerability to tobacco dependence, in particular variation in the CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptor (nAChR) subunit gene cluster, will be discussed. Third, the role of the habenular complex in nicotine aversion, primarily medial habenular projections to the interpeduncular nucleus (IPN) but also lateral habenular projections to rostromedial tegmental nucleus (RMTg) and ventral tegmental area (VTA) are reviewed. Forth, brain circuits that are enriched in nAChRs, but whose role in nicotine avoidance has not yet been assessed, will be proposed. Finally, the feasibility of developing novel therapeutic agents for tobacco dependence that act not by blocking nicotine reward but by enhancing nicotine avoidance will be considered. PMID:24055497

Opname van nicotine door kippen en overdracht naar eieren bij toepassing van nicotine tegen bloedluis

NARCIS (Netherlands)

Traag, W.A.; Rijk, de T.C.; Zomer, P.; Vos Van Avezathe, A.; Kan, C.A.; Zeilmaker, M.; Hoogenboom, L.A.P.

2005-01-01

Uit onderzoek van de AID blijkt nicotine gebruikt te worden voor de bestrijding van bloedluis bij kippen. Dit levert mogelijk gezondheidsrisico's op voor de consument van het kippenvlees of de eieren. Omdat niet duidelijk is of het nicotine na de bestrijding van bloedluis in het vlees of eieren

Design, formulation and evaluation of nicotine chewing gum

OpenAIRE

Abolfazl Aslani; Sahar Rafiei

2012-01-01

Background: Nicotine replacement therapy (NRT) can help smokers to quit smoking. Nicotine chewing gum has attracted the attention from pharmaceutical industries to offer it to consumers as an easily accessible NRT product. However, the bitter taste of such gums may compromise their acceptability by patients. This study was, therefore, designed to develop 2 and 4 mg nicotine chewing gums of pleasant taste, which satisfy the consumers the most. Materials and Methods: Nicotine, sugar, liquid...

A behavioral economic analysis of the value-enhancing effects of nicotine and varenicline and the role of nicotinic acetylcholine receptors in male and female rats.

Science.gov (United States)

Barrett, Scott T; Geary, Trevor N; Steiner, Amy N; Bevins, Rick A

2018-04-09

Reinforcement value enhancement by nicotine of non-nicotine rewards is believed to partially motivate smoking behavior. Recently, we showed that the value-enhancing effects of nicotine are well characterized by reinforcer demand models and that the value-enhancing effects of the smoking-cessation aid bupropion (Zyban) are distinct from those of nicotine and differ between the sexes. The present study evaluated potential sex differences in the enhancement effects of nicotine and varenicline (Chantix) using a reinforcer demand methodology. The role of α4β2* and α7 nicotinic acetylcholine receptors (nAChRs) in the enhancing effects of nicotine and varenicline is also evaluated. Male and female rats (n=12/sex) were trained to lever press maintained by sensory reinforcement by visual stimulus (VS) presentations. Changes in the VS value following nicotine and varenicline administration were assessed using an established reinforcer demand approach. Subsequently, the effects of antagonism of α4β2* and α7 nAChRs on varenicline and nicotine-induced enhancement active lever-pressing were assessed using a progressive ratio schedule. Nicotine and varenicline enhanced VS demand equivalently between the sexes as evaluated by reinforcer demand. However, α4β2* receptor antagonism attenuated value enhancement by nicotine and varenicline in females, but only of nicotine in males.

Nicotinic activation of laterodorsal tegmental neurons

DEFF Research Database (Denmark)

Ishibashi, Masaru; Leonard, Christopher S; Kohlmeier, Kristi A

2009-01-01

Identifying the neurological mechanisms underlying nicotine reinforcement is a healthcare imperative, if society is to effectively combat tobacco addiction. The majority of studies of the neurobiology of addiction have focused on dopamine (DA)-containing neurons of the ventral tegmental area (VTA......). However, recent data suggest that neurons of the laterodorsal tegmental (LDT) nucleus, which sends cholinergic, GABAergic, and glutamatergic-containing projections to DA-containing neurons of the VTA, are critical to gating normal functioning of this nucleus. The actions of nicotine on LDT neurons...... are unknown. We addressed this issue by examining the effects of nicotine on identified cholinergic and non-cholinergic LDT neurons using whole-cell patch clamp and Ca(2+)-imaging methods in brain slices from mice (P12-P45). Nicotine applied by puffer pipette or bath superfusion elicited membrane...

Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

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Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

2017-06-01

Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p nicotine dependence (p Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and

New trends in the treatment of nicotine addiction.

Science.gov (United States)

Sliwińska-Mossoń, Mariola; Zieleń, Iwona; Milnerowicz, Halina

2014-01-01

The aim of this study was to discuss the therapeutic substances used to treat nicotine addiction, not registered in Poland. This paper presents the results of the latest clinical trials and the possibility of their use in the treatment of nicotine addiction. The first two discussed drugs clonidine and nortriptyline are recommended by clinical practice guidelines AHRQ (Agency for Healthcare Research and Quality) as the substance of the second line in the fight against addiction. Nortriptyline belongs to tricyclic antidepressants. Its mechanism of action is the inhibition of the reuptake of norepinephrine. It is suggested as the antagonist of activity of nicotinic receptors. The results confirm its efficacy in the treatment of nicotine addiction, but many side effects limit its use. Clonidine acts presumably by inhibition of sympathetic hyperactivity characteristic of symptoms associated with nicotine rehab. The remaining compounds under discussion, such as: venlafaxine, fluoxetine, moclobemide and rimonabant, are not registered in any country with an indication to use in the treatment of nicotine addiction, however, due to the mechanism in which they act, the possibility of their use in the treatment of this disease is considered. The possibility of using anxiolytics such as: buspirone, diazepam, meprobamate and beta-blockers: metoprolol and oxprenolol is also considered in order to treat the anxiety appearing as one of the symptoms of abstinence. An interesting proposal to combat nicotine addiction are vaccines--NicVAX, CYT002-NicQb and TA-NIC. Currently, they are in clinical phase I and II of their development. Their operation would be based on the induction of specific antibodies that bind nicotine in the plasma, thus prevent it reaching the nicotinic receptors. Preliminary results confirm the possible positive effects in the prevention and treatment of nicotine addiction.

NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

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Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

2009-01-01

Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug.

Effects of adolescent treatment with nicotine, harmane, or norharmane in male Sprague-Dawley rats.

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Goodwin, Amy K; Lantz-McPeak, Susan M; Robinson, Bonnie L; Law, C Delbert; Ali, Syed F; Ferguson, Sherry A

2015-01-01

The initiation of tobacco use occurs most often in adolescence and may be especially detrimental as the adolescent brain is undergoing substantial development. In addition to nicotine, there are over 9000 other compounds present in tobacco products, including the β-carbolines harmane and norharmane. The present study aimed to determine the long-term effects of adolescent exposure to nicotine (NIC), harmane (HAR), or norharmane (NOR) on locomotor activity, learning and memory, anxiety-like behavior, motor coordination, and monoamine/metabolite concentrations in the striatum and nucleus accumbens of male Sprague-Dawley rats. Beginning on postnatal day (PND) 27 and continuing through PND 55, subjects received twice daily intraperitoneal injections of 1ml/kg saline (CON), 0.5mg NIC/kg, 0.5mg HAR/kg, or 0.5mg NOR/kg. Body weight, food, and water intake were measured daily (PNDs 27-96). Locomotor activity was assessed on PND 40 or 41, PND 55, and PNDs 81 and 82. Other behaviors (anxiety-like behavior, motor coordination, and spatial learning and memory) were assessed at least 25 days after drug exposure ended (PNDs 80-91). On PND 97, subjects were decapitated and the striatum and nucleus accumbens were dissected and frozen for analysis. NIC treatment significantly decreased food intake, but did not alter locomotor activity during or after treatment. HAR and NOR treatment, however, caused significant open field hypoactivity. Motor coordination, water maze performance, and concentrations of monoamines and metabolites in the striatum and nucleus accumbens were unaltered by any drug treatment. These results indicate a long-lasting effect on activity levels from adolescent HAR or NOR treatment; however, there were few long-lasting NIC effects. Given the paucity of data describing effects of HAR or NOR exposure, these data should encourage additional studies of these tobacco constituents as well as constituent combination studies. Published by Elsevier Inc.

Alcohol's actions on neuronal nicotinic acetylcholine receptors.

Science.gov (United States)

Davis, Tiffany J; de Fiebre, Christopher M

2006-01-01

Although it has been known for many years that alcoholism and tobacco addiction often co-occur, relatively little information is available on the biological factors that regulate the co-use and abuse of nicotine and alcohol. In the brain, nicotine acts at several different types of receptors collectively known as nicotinic acetylcholine receptors (nAChRs). Alcohol also acts on at least some of these receptors, enhancing the function of some nAChR subtypes and inhibiting the activity of others. Chronic alcohol and nicotine administration also lead to changes in the numbers of nAChRs. Natural variations (i.e., polymorphisms) in the genes encoding different nAChR subunits may be associated with individual differences in the sensitivity to some of alcohol's and nicotine's effects. Finally, at least one subtype of nAChR may help protect cells against alcohol-induced neurotoxicity.

Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

Directory of Open Access Journals (Sweden)

Paul Fredrickson

2014-01-01

Full Text Available Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13 analog, blocks behavioral sensitization (an animal model for psychostimulant addiction to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

Nicotinic and iso nicotinic acids: interactions with gamma radiation and acid-base equilibrium

International Nuclear Information System (INIS)

Ribeiro, Z.A.

1984-01-01

The values of pKa 1 and pKa 2 for nicotinic and iso nicotinic acids in aqueous medium were determined. The effects of gamma radiation about these acids by infrared and ultraviolet spectrophotometry and thermal gravimetric analysis were also studied. It was verified that the radiolysis of acids occurred by the two process of first order, determining the degradation constant and the degradation factors for each one of the solutions. (C.G.C.)

Reduced Nicotine Content Expectancies Affect Initial Responses to Smoking.

Science.gov (United States)

Mercincavage, Melissa; Smyth, Joshua M; Strasser, Andrew A; Branstetter, Steven A

2016-10-01

We sought to determine if negative responses to reduced nicotine content (RNC) cigarettes during open-label trials result from smokers' (negative) expectancies. We examined the effects of nicotine content description - independent of actual nicotine content - on subjective responses (craving reduction, withdrawal suppression, mood changes, and sensory ratings) and smoking behaviors (topography measures and carbon monoxide [CO] boost). Thirty-six 12-hour-abstinent daily smokers completed a 3-session crossover trial. During each session, participants smoked their preferred brand cigarette - blinded and described as containing "usual," "low," and "very low" nicotine content - through a topography device and completed CO and subjective response assessments. Although nicotine content was identical, compared to the "usual" content cigarette, participants experienced less craving reduction after smoking the "very low" nicotine cigarette, and rated its smoke as weaker (p marketing and labeling are likely important considerations if a federal nicotine reduction policy is initiated.

Serotonergic modulation of nicotine-induced kinetic tremor in mice

Directory of Open Access Journals (Sweden)

Naofumi Kunisawa

2017-06-01

Full Text Available We previously demonstrated that nicotine elicited kinetic tremor by elevating the neural activity of the inferior olive via α7 nicotinic acetylcholine (nACh receptors. Since α7 nACh receptors reportedly facilitate synaptic monoamine release, we explored the role of 5-HT receptors in induction and/or modulation of nicotine tremor. Treatment of mice with nicotine induced kinetic tremor that normally appeared during movement. The 5-HT1A agonist, 8-hydroxydipropylaminotetraline (8-OH-DPAT, significantly enhanced nicotine-induced tremor and the action of 8-OH-DPAT was antagonized by WAY-100135 (5-HT1A antagonist. In addition, the cerebral 5-HT depletion by repeated treatment with p-chlorophenylalanine did not reduce, but rather potentiated the facilitatory effects of 8-OH-DPAT. In contrast, the 5-HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI, significantly attenuated nicotine tremor, which was antagonized by ritanserin (5-HT2 antagonist. The 5-HT3 agonist SR-57227 did not affect nicotine-induced tremor. Furthermore, when testing the direct actions of 5-HT antagonists, nicotine tremor was inhibited by WAY-100135, but was unaffected by ritanserin, ondansetron (5-HT3 antagonist or SB-258585 (5-HT6 antagonist. These results suggest that postsynaptic 5-HT1A receptors are involved in induction of nicotine tremor mediated by α7 nACh receptors. In addition, 5-HT2 receptors have an inhibitory modulatory role in induction of nicotine tremor.

Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence

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Lingjun Zuo

2016-11-01

Full Text Available It has been hypothesized that the nicotinic acetylcholine receptors (nAChRs play important roles in nicotine dependence (ND and influence the number of cigarettes smoked per day (CPD in smokers. We compiled the associations between nicotinic cholinergic receptor genes (CHRNs and ND/CPD that were replicated across different studies, reviewed the expression of these risk genes in human/mouse brains, and verified their expression using independent samples of both human and mouse brains. The potential functions of the replicated risk variants were examined using cis-eQTL analysis or predicted using a series of bioinformatics analyses. We found replicated and significant associations for ND/CPD at 19 SNPs in six genes in three genomic regions (CHRNB3-A6, CHRNA5-A3-B4 and CHRNA4. These six risk genes are expressed in at least 18 distinct areas of the human/mouse brain, with verification in our independent human and mouse brain samples. The risk variants might influence the transcription, expression and splicing of the risk genes, alter RNA secondary or protein structure. We conclude that the replicated associations between CHRNB3-A6, CHRNA5-A3-B4, CHRNA4 and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD.

Prior nicotine self-administration attenuates subsequent dopaminergic deficits of methamphetamine in rats: role of nicotinic acetylcholine receptors.

Science.gov (United States)

Baladi, Michelle G; Nielsen, Shannon M; McIntosh, J Michael; Hanson, Glen R; Fleckenstein, Annette E

2016-08-01

Preclinical studies have demonstrated that oral nicotine exposure attenuates long-term dopaminergic damage induced by toxins, including repeated, high doses of methamphetamine. It is suggested that alterations in nicotinic acetylcholine receptor (nAChR) expression, including α4β2* and α6β2* subtypes, likely contribute to this protection. The current study extended these findings by investigating whether nicotine self-administration in male, Sprague-Dawley rats (a) attenuates short-term dopaminergic damage induced by methamphetamine and (b) causes alterations in levels of α4β2* and α6β2* nAChR subtypes. The findings indicate that nicotine self-administration (0.032 mg/kg/infusion for 14 days) per se did not alter α4β2* and α6β2* nAChR expression or dopamine transporter (DAT) expression and function. Interestingly, prior nicotine self-administration attenuated methamphetamine-induced decreases in DAT function when assessed 24 h, but not 1 h, after methamphetamine treatment (4×7.5 mg/kg/injection). The ability of nicotine to attenuate the effects of methamphetamine on DAT function corresponded with increases in α4β2*, but not α6β2*, nAChR binding density. Understanding the role of nAChRs in methamphetamine-induced damage has the potential to elucidate mechanisms underlying the etiology of disorders involving dopaminergic dysfunction, as well as to highlight potential new therapeutic strategies for prevention or reduction of dopaminergic neurodegeneration.

Nicotine Gum

Science.gov (United States)

... with a smoking cessation program, which may include support groups, counseling, or specific behavioral change techniques. Nicotine gum ... and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or ...

Animal Research on Nicotine Reduction: Current Evidence and Research Gaps.

Science.gov (United States)

Smith, Tracy T; Rupprecht, Laura E; Denlinger-Apte, Rachel L; Weeks, Jillian J; Panas, Rachel S; Donny, Eric C; Sved, Alan F

2017-09-01

A mandated reduction in the nicotine content of cigarettes may improve public health by reducing the prevalence of smoking. Animal self-administration research is an important complement to clinical research on nicotine reduction. It can fill research gaps that may be difficult to address with clinical research, guide clinical researchers about variables that are likely to be important in their own research, and provide policy makers with converging evidence between clinical and preclinical studies about the potential impact of a nicotine reduction policy. Convergence between clinical and preclinical research is important, given the ease with which clinical trial participants can access nonstudy tobacco products in the current marketplace. Herein, we review contributions of preclinical animal research, with a focus on rodent self-administration, to the science of nicotine reduction. Throughout this review, we highlight areas where clinical and preclinical research converge and areas where the two differ. Preclinical research has provided data on many important topics such as the threshold for nicotine reinforcement, the likelihood of compensation, moderators of the impact of nicotine reduction, the impact of environmental stimuli on nicotine reduction, the impact of nonnicotine cigarette smoke constituents on nicotine reduction, and the impact of nicotine reduction on vulnerable populations. Special attention is paid to current research gaps including the dramatic rise in alternative tobacco products, including electronic nicotine delivery systems (ie, e-cigarettes). The evidence reviewed here will be critical for policy makers as well as clinical researchers interested in nicotine reduction. This review will provide policy makers and clinical researchers interested in nicotine reduction with an overview of the preclinical animal research conducted on nicotine reduction and the regulatory implications of that research. The review also highlights the utility of

Antifungal activity of nicotine and its cobalt complex

International Nuclear Information System (INIS)

Zaidi, M.I.; Gul, A.

2005-01-01

Nicotine and its metal complex; Co(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activity against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cobalt(II) chloride was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine had antifungal activity against all species of fungi studied except Candida albicans, Microsporum canis, Epidermophyton floccosum, Candida tropicalis, and Alternaria infectoria. Cobalt(II) nicotine was found to be effective against all selected species of fungi but ineffective against Candida solani, Penicillium notalum, Microsporum canis, Fusarium solani and Fusarium moniliforme. (author)

Knowledge and Perceptions about Nicotine, Nicotine Replacement Therapies and Electronic Cigarettes among Healthcare Professionals in Greece

Directory of Open Access Journals (Sweden)

Anastasia Moysidou

2016-05-01

Full Text Available Introduction. The purpose of this study was to evaluate the knowledge and perceptions of Greek healthcare professionals about nicotine, nicotine replacement therapies and electronic cigarettes. Methods. An online survey was performed, in which physicians and nurses working in private and public healthcare sectors in Athens-Greece were asked to participate through email invitations. A knowledge score was calculated by scoring the correct answers to specific questions with 1 point. Results. A total of 262 healthcare professionals were included to the analysis. Most had daily contact with smokers in their working environment. About half of them considered that nicotine has an extremely or very important contribution to smoking-related disease. More than 30% considered nicotine replacement therapies equally or more addictive than smoking, 76.7% overestimated their smoking cessation efficacy and only 21.0% would recommend them as long-term smoking substitutes. For electronic cigarettes, 45.0% considered them equally or more addictive than smoking and 24.4% equally or more harmful than tobacco cigarettes. Additionally, 35.5% thought they involve combustion while the majority responded that nicotine in electronic cigarettes is synthetically produced. Only 14.5% knew about the pending European regulation, but 33.2% have recommended them to smokers in the past. Still, more than 40% would not recommend electronic cigarettes to smokers unwilling or unable to quit smoking with currently approved medications. Cardiologists and respiratory physicians, who are responsible for smoking cessation therapy in Greece, were even more reluctant to recommend electronic cigarettes to this subpopulation of smokers compared to all other participants. The knowledge score of the whole study sample was 7.7 (SD: 2.4 out of a maximum score of 16. Higher score was associated with specific physician specialties. Conclusions. Greek healthcare professionals appear to overestimate

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

Science.gov (United States)

Christensen, Mark H.; Ishibashi, Masaru; Nielsen, Michael L.; Leonard, Christopher S.; Kohlmeier, Kristi A.

2015-01-01

The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on several parameters affecting LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7-P15), nicotine was found to induce larger intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a greater degree in younger animals, possibly linked to development associated differences found in nicotinic effects on action potential shape and afterhyperpolarization. We conclude that in addition to age-associated alterations of several properties expected to affect resting cell excitability, parameters affecting cell excitability are altered by nicotine differentially across ontogeny. Taken together, our data suggest that nicotine induces a larger excitatory response in cholinergic LDT neurons from the youngest animals, which could result in a greater excitatory output from these cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across age. PMID:24863041

Alpha5 nicotinic acetylcholine receptor mediates nicotine-induced HIF-1α and VEGF expression in non-small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Ma, Xiaoli; Jia, Yanfei; Zu, Shanshan [Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013 (China); Li, Ruisheng [Institute of Infectious Diseases, 302 Military Hospital, Beijing 100039 (China); Jia, Ying; Zhao, Yun; Xiao, Dongjie [Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013 (China); Dang, Ningning [Department of Dermatology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013 (China); Wang, Yunshan [Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013 (China)

2014-07-15

By binding to nicotinic acetylcholine receptors (nAChRs), nicotine induces the proliferation and apoptosis of non-small cell lung cancer (NSCLC). Previous studies have indicated that α5-nAChR is highly associated with lung cancer risk and nicotine dependence. However, the mechanisms through which α5-nAChRs may influence lung carcinogenesis are far from clear. In the present study, we investigated the roles of α5-nAChR in the nicotine-induced expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Immunohistochemistry was used to detect the expression of α5-nAChR and HIF-1α in 60 specimens of lung cancer and para-carcinoma tissue. The correlations between the expression levels of α5-nAChR and HIF-1α and other clinicopathological data were analyzed. In a cell line that highly expressed α5-nAChR, the loss of α5-nAChR function by siRNA was used to study whether α5-nAChR is involved in the nicotine-induced expression of HIF-1α and VEGF through the activation of the ERK1/2 and PI3K/Akt signaling pathways. Cell growth was detected using the cell counting kit-8 (CCK-8). α5-nAChR (78.3%) and HIF-1α (88.3%) were both overexpressed in NSCLC, and their expression levels were found to be correlated with each other (P < 0.05). In the A549 cell line, α5-nAChR and HIF-1α were found to be expressed under normal conditions, and their expression levels were significantly increased in response to nicotine treatment. The silencing of α5-nAChR significantly inhibited the nicotine-induced cell proliferation compared with the control group and attenuated the nicotine-induced upregulation of HIF-1α and VEGF, and these effects required the cooperation of the ERK1/2 and PI3K/Akt signaling pathways. These results show that the α5-nAChR/HIF-1α/VEGF axis is involved in nicotine-induced tumor cell proliferation, which suggests that α5-nAChR may serve as a potential anticancer target in nicotine-associated lung cancer. - Highlights

Alpha5 nicotinic acetylcholine receptor mediates nicotine-induced HIF-1α and VEGF expression in non-small cell lung cancer

International Nuclear Information System (INIS)

Ma, Xiaoli; Jia, Yanfei; Zu, Shanshan; Li, Ruisheng; Jia, Ying; Zhao, Yun; Xiao, Dongjie; Dang, Ningning; Wang, Yunshan

2014-01-01

By binding to nicotinic acetylcholine receptors (nAChRs), nicotine induces the proliferation and apoptosis of non-small cell lung cancer (NSCLC). Previous studies have indicated that α5-nAChR is highly associated with lung cancer risk and nicotine dependence. However, the mechanisms through which α5-nAChRs may influence lung carcinogenesis are far from clear. In the present study, we investigated the roles of α5-nAChR in the nicotine-induced expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Immunohistochemistry was used to detect the expression of α5-nAChR and HIF-1α in 60 specimens of lung cancer and para-carcinoma tissue. The correlations between the expression levels of α5-nAChR and HIF-1α and other clinicopathological data were analyzed. In a cell line that highly expressed α5-nAChR, the loss of α5-nAChR function by siRNA was used to study whether α5-nAChR is involved in the nicotine-induced expression of HIF-1α and VEGF through the activation of the ERK1/2 and PI3K/Akt signaling pathways. Cell growth was detected using the cell counting kit-8 (CCK-8). α5-nAChR (78.3%) and HIF-1α (88.3%) were both overexpressed in NSCLC, and their expression levels were found to be correlated with each other (P < 0.05). In the A549 cell line, α5-nAChR and HIF-1α were found to be expressed under normal conditions, and their expression levels were significantly increased in response to nicotine treatment. The silencing of α5-nAChR significantly inhibited the nicotine-induced cell proliferation compared with the control group and attenuated the nicotine-induced upregulation of HIF-1α and VEGF, and these effects required the cooperation of the ERK1/2 and PI3K/Akt signaling pathways. These results show that the α5-nAChR/HIF-1α/VEGF axis is involved in nicotine-induced tumor cell proliferation, which suggests that α5-nAChR may serve as a potential anticancer target in nicotine-associated lung cancer. - Highlights

Lipid-drug-conjugate (LDC) solid lipid nanoparticles (SLN) for the delivery of nicotine to the oral cavity - optimization of nicotine loading efficiency.

Science.gov (United States)

Ding, Yuan; Nielsen, Kent A; Nielsen, Bruno P; Bøje, Niels W; Müller, Rainer H; Pyo, Sung Min

2018-03-12

Nicotine, obtained from tobacco leaves, has been used to promote the cessation of smoking and reduce the risk of COPD and lung cancer. Incorporating the active in lipid nanoparticles is an effective tool to minimize its irritation potential and to use the particles as intermediate to produce final products. However, as a hydrophilic active, it is a challenge to prepare nicotine loaded lipid nanoparticles with high drug loading. In this study, lipid-drug-conjugates (LDC) were formed by nicotine and different fatty acids to enable the production of sufficiently loaded nicotine lipid nanoparticles. The encapsulation efficiency of nicotine in LDC-containing SLN was about 50%, which increased at least fourfold compared to the non-LDC formulations (around 10%) due to the increased lipophilicity of nicotine by strong interactions between positively charged nicotine and negatively charged fatty acids (formation of LDCs). The z-average of all formulations (150 to 350 nm) proved to be in the required submicron size range with a narrow size distribution. In summary, nicotine loaded LDC lipid nanoparticles with high drug loading were successfully developed with Kolliwax® S and stearic acid as counter-ion forming the LDC and hydrogenated sunflower oil (HSO) as lipid particle matrix. Copyright © 2018. Published by Elsevier B.V.

Epidemiology, radiology, and genetics of nicotine dependence in COPD

Directory of Open Access Journals (Sweden)

Hokanson John E

2011-01-01

Full Text Available Abstract Background Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers. Methods Current smokers with COPD (GOLD stage ≥ 2 or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND. Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung Results Among 842 currently smoking subjects (335 COPD cases and 507 controls, 329 subjects (39.1% showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (ρ = -0.19, p Conclusions Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes. Trial registration ClinicalTrials (NCT: NCT00608764

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

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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 promotes cell proliferation and induces resistance to cisplatin by α7 nicotinic acetylcholine receptor‑mediated activation in Raw264.7 and El4 cells.

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Wang, Yan Yan; Liu, Yao; Ni, Xiao Yan; Bai, Zhen Huan; Chen, Qiong Yun; Zhang, Ye; Gao, Feng Guang

2014-03-01

Although nicotine is a risk factor for carcinogenesis and atherosclerosis, epidemiological data indicate that nicotine has therapeutic benefits in treating Alzheimer's disease. Our previous studies also showed that nicotine-treated dendritic cells have potential antitumor effects. Hence, the precise effects of nicotine on the biological characterizations of cells are controversial. The aim of the present study was to assess the roles of α7 nicotinic acetylcholine receptors (nAChRs), Erk1/2-p38-JNK and PI3K-Akt pathway in nicotine-mediated proliferation and anti-apoptosis effects. The results firstly showed that nicotine treatment clearly augmented cell viability and upregulated PCNA expression in both Raw264.7 and El4 cells. Meanwhile, nicotine afforded protection against cisplatin-induced toxicity through inhibiting caspase-3 activation and upregulating anti-apoptotic protein expression. Further exploration demonstrated that nicotine efficiently abolished cisplatin-promoted mitochondria translocation of Bax and the release of cytochrome c. The pretreatment of α-bungarotoxin and tubocurarine chloride significantly attenuated nicotine-augmented cell viability, abolished caspase-3 activation and α7 nAChR upregulation. Both Erk-JNK-p38 and PI3K-Akt signaling pathways could be activated by nicotine treatment in Raw264.7 and El4 cells. Notably, when Erk-JNK and PI3K-Akt activities were inhibited, nicotine-augmented cell proliferation and anti-apoptotic effects were abolished accordingly. The results presented here indicate that nicotine could achieve α7 nAChR-mediated proliferation and anti-apoptotic effects by activating Erk-JNK and PI3K-Akt pathways respectively, providing potential therapeutic molecules to deal with smoking-associated human diseases.

Serotonergic modulation of nicotine-induced kinetic tremor in mice.

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Kunisawa, Naofumi; Iha, Higor A; Nomura, Yuji; Onishi, Misaki; Matsubara, Nami; Shimizu, Saki; Ohno, Yukihiro

2017-06-01

We previously demonstrated that nicotine elicited kinetic tremor by elevating the neural activity of the inferior olive via α7 nicotinic acetylcholine (nACh) receptors. Since α7 nACh receptors reportedly facilitate synaptic monoamine release, we explored the role of 5-HT receptors in induction and/or modulation of nicotine tremor. Treatment of mice with nicotine induced kinetic tremor that normally appeared during movement. The 5-HT 1A agonist, 8-hydroxydipropylaminotetraline (8-OH-DPAT), significantly enhanced nicotine-induced tremor and the action of 8-OH-DPAT was antagonized by WAY-100135 (5-HT 1A antagonist). In addition, the cerebral 5-HT depletion by repeated treatment with p-chlorophenylalanine did not reduce, but rather potentiated the facilitatory effects of 8-OH-DPAT. In contrast, the 5-HT 2 agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), significantly attenuated nicotine tremor, which was antagonized by ritanserin (5-HT 2 antagonist). The 5-HT 3 agonist SR-57227 did not affect nicotine-induced tremor. Furthermore, when testing the direct actions of 5-HT antagonists, nicotine tremor was inhibited by WAY-100135, but was unaffected by ritanserin, ondansetron (5-HT 3 antagonist) or SB-258585 (5-HT 6 antagonist). These results suggest that postsynaptic 5-HT 1A receptors are involved in induction of nicotine tremor mediated by α7 nACh receptors. In addition, 5-HT 2 receptors have an inhibitory modulatory role in induction of nicotine tremor. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol

Science.gov (United States)

Versaggi, Cassandra L.; King, Christopher P.; Meyer, Paul J.

2016-01-01

Rationale Some individuals are particularly responsive to reward-associated stimuli (“cues”), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. Objectives To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food predictive cue (“sign-trackers”) or a reward-delivery location (“goal-trackers”). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Methods Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Results Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue, and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Conclusions Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs. PMID:27282365

The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol.

Science.gov (United States)

Versaggi, Cassandra L; King, Christopher P; Meyer, Paul J

2016-08-01

Some individuals are particularly responsive to reward-associated stimuli ("cues"), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food-predictive cue ("sign-trackers") or a reward-delivery location ("goal-trackers"). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue-induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs.

GLP-1 acts on habenular avoidance circuits to control nicotine intake.

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Tuesta, Luis M; Chen, Zuxin; Duncan, Alexander; Fowler, Christie D; Ishikawa, Masago; Lee, Brian R; Liu, Xin-An; Lu, Qun; Cameron, Michael; Hayes, Matthew R; Kamenecka, Theodore M; Pletcher, Matthew; Kenny, Paul J

2017-05-01

Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake. Conversely, Glp1r knockout mice consumed greater quantities of nicotine than wild-type mice. Using optogenetic stimulation, we show that GLP-1 excites medial habenular (MHb) projections to the interpeduncular nucleus (IPN). Activation of GLP-1 receptors in the MHb-IPN circuit abolished nicotine reward and decreased nicotine intake, whereas their knockdown or pharmacological blockade increased intake. GLP-1 neurons may therefore serve as 'satiety sensors' for nicotine that stimulate habenular systems to promote nicotine avoidance before its aversive effects are encountered.

The effect of coniine on presynaptic nicotinic receptors.

Science.gov (United States)

Erkent, Ulkem; Iskit, Alper B; Onur, Rustu; Ilhan, Mustafa

2016-01-01

Toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), is manifested by characteristic nicotinic clinical signs including excitement, depression, hypermetria, seizures, opisthotonos via postsynaptic nicotinic receptors. There is limited knowledge about the role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine in the literature. The present study was undertaken to evaluate the possible role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine. For this purpose, the rat anococcygeus muscle and guinea-pig atria were used in vitro. Nicotine (100 μM) elicited a biphasic response composed of a relaxation followed by contraction through the activation of nitrergic and noradrenergic nerve terminals in the phenylephrine-contracted rat anococcygeus muscle. Coniine inhibited both the nitrergic and noradrenergic response in the muscle (-logIC(50) = 3.79 ± 0.11 and -logIC(50) = 4.57 ± 0.12 M, respectively). The effect of coniine on nicotinic receptor-mediated noradrenergic transmission was also evaluated in the guinea-pig atrium (-logIC(50) = 4.47 ± 0.12 M) and did not differ from the -logIC(50) value obtained in the rat anococcygeus muscle. This study demonstrated that coniine exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response.

Neuronal effects of nicotine during auditory selective attention.

Science.gov (United States)

Smucny, Jason; Olincy, Ann; Eichman, Lindsay S; Tregellas, Jason R

2015-06-01

Although the attention-enhancing effects of nicotine have been behaviorally and neurophysiologically well-documented, its localized functional effects during selective attention are poorly understood. In this study, we examined the neuronal effects of nicotine during auditory selective attention in healthy human nonsmokers. We hypothesized to observe significant effects of nicotine in attention-associated brain areas, driven by nicotine-induced increases in activity as a function of increasing task demands. A single-blind, prospective, randomized crossover design was used to examine neuronal response associated with a go/no-go task after 7 mg nicotine or placebo patch administration in 20 individuals who underwent functional magnetic resonance imaging at 3T. The task design included two levels of difficulty (ordered vs. random stimuli) and two levels of auditory distraction (silence vs. noise). Significant treatment × difficulty × distraction interaction effects on neuronal response were observed in the hippocampus, ventral parietal cortex, and anterior cingulate. In contrast to our hypothesis, U and inverted U-shaped dependencies were observed between the effects of nicotine on response and task demands, depending on the brain area. These results suggest that nicotine may differentially affect neuronal response depending on task conditions. These results have important theoretical implications for understanding how cholinergic tone may influence the neurobiology of selective attention.

The effects of Nicotinic Acid and Xanthinol Nicotinate on human memory in different categories of age

NARCIS (Netherlands)

Loriaux, S.M.; Deijen, J.B.; Orlebeke, J.F.; de Swart, J.H.

1985-01-01

The treatment effect of nicotinic acid and xanthinol nicotinate on human memory was compared with placebo in 96 healthy subjects. Forty-three subjects were young (35-45 years), 30 subjects middle aged (55-65 years) and 23 subjects were old aged (75-85 years). Pre- and post-treatment scores were

21 CFR 172.310 - Aluminum nicotinate.

Science.gov (United States)

2010-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be safely...

VOLTAMMETRIC DETERMINATION OF NICOTINE IN CIGARETTE ...

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determination of nicotine in two brands of commercial cigarettes and ... to disruption of arteries and cardiovascular risk factors [8, 9]. Smoking .... e d. Figure 2. Cyclic voltammetric response (scan rate of 100 mV/s) of 1.0 mM nicotine at AGCE in.

Chronic oral nicotine increases brain [3H]epibatidine binding and responsiveness to antidepressant drugs, but not nicotine, in the mouse forced swim test

DEFF Research Database (Denmark)

Andreasen T., Jesper; Nielsen, Elsebet O; Redrobe, John P

2009-01-01

Smoking rates among depressed individuals is higher than among healthy subjects, and nicotine alleviates depressive symptoms. Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. In mice, acute nicotine administration enhances...... the activity of antidepressants in the mouse forced swim (mFST) and tail suspension tests. Here, we investigated if this action of nicotine is also reflected in a chronic treatment regimen....

Electronic Nicotine Delivery Systems Key Facts Infographic

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U.S. Department of Health & Human Services — Explore the Electronic Nicotine Delivery Systems Key Facts Infographic which outlines key facts related to electronic nicotine delivery systems (ENDS), including...

Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors

International Nuclear Information System (INIS)

Magata, Yasuhiro; Kitano, Haruhiro; Shiozaki, Toshiki; Iida, Yasuhiko; Nishizawa, Sadahiko; Saji, Hideo; Konishi, Junji

2000-01-01

The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3 H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125 I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions

Thermal behaviour of nicotinic acid, sodium nicotinate and its compounds with some bivalent transition metal ions

Energy Technology Data Exchange (ETDEWEB)

Nascimento, A.L.C.S. do; Caires, F.J., E-mail: caires.flavio@yahoo.com.br; Gomes, D.J.C.; Gigante, A.C.; Ionashiro, M.

2014-01-10

Graphical abstract: - Highlights: • The transition metal ion nicotinates were synthesized. • The TG–DTA curves provided previously unreported information about thermal behaviour. • The gaseous products released were detected by TG–DSC coupled to FTIR. - Abstract: Solid-state M(L){sub 2}·nH{sub 2}O compounds, where M stands for bivalent transition metals (Mn, Fe, Co, Ni, Cu and Zn), L is nicotinate and n = 0–4.5, have been synthesized. Characterization and thermal behaviour of these compounds were investigated employing elemental analysis based on the mass losses observed in the TG–DTA curves, complexometry, X-ray diffractometry, infrared spectroscopy (FTIR), simultaneous thermogravimetric and differential thermal analysis (TG–DTA) and TG–DSC coupled to FTIR. The thermal behaviour of nicotinic acid and its sodium salt was also investigated. For the hydrated transition metal compounds, the dehydration and thermal decomposition of the anhydrous compounds occur in a single step. For the sodium nicotinate, the final residue up to 765 °C is sodium carbonate and for the transition metal nicotinates, the final residues are Mn{sub 3}O{sub 4}, Fe{sub 2}O{sub 3}, Co{sub 3}O{sub 4}, NiO, CuO and ZnO. The results also provided information concerning the thermal stability, thermal decomposition and identification of the gaseous products evolved during the thermal decomposition of the compounds.

Thermal behaviour of nicotinic acid, sodium nicotinate and its compounds with some bivalent transition metal ions

International Nuclear Information System (INIS)

Nascimento, A.L.C.S. do; Caires, F.J.; Gomes, D.J.C.; Gigante, A.C.; Ionashiro, M.

2014-01-01

Graphical abstract: - Highlights: • The transition metal ion nicotinates were synthesized. • The TG–DTA curves provided previously unreported information about thermal behaviour. • The gaseous products released were detected by TG–DSC coupled to FTIR. - Abstract: Solid-state M(L) 2 ·nH 2 O compounds, where M stands for bivalent transition metals (Mn, Fe, Co, Ni, Cu and Zn), L is nicotinate and n = 0–4.5, have been synthesized. Characterization and thermal behaviour of these compounds were investigated employing elemental analysis based on the mass losses observed in the TG–DTA curves, complexometry, X-ray diffractometry, infrared spectroscopy (FTIR), simultaneous thermogravimetric and differential thermal analysis (TG–DTA) and TG–DSC coupled to FTIR. The thermal behaviour of nicotinic acid and its sodium salt was also investigated. For the hydrated transition metal compounds, the dehydration and thermal decomposition of the anhydrous compounds occur in a single step. For the sodium nicotinate, the final residue up to 765 °C is sodium carbonate and for the transition metal nicotinates, the final residues are Mn 3 O 4 , Fe 2 O 3 , Co 3 O 4 , NiO, CuO and ZnO. The results also provided information concerning the thermal stability, thermal decomposition and identification of the gaseous products evolved during the thermal decomposition of the compounds

Design, formulation and evaluation of nicotine chewing gum.

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Aslani, Abolfazl; Rafiei, Sahar

2012-01-01

Nicotine replacement therapy (NRT) can help smokers to quit smoking. Nicotine chewing gum has attracted the attention from pharmaceutical industries to offer it to consumers as an easily accessible NRT product. However, the bitter taste of such gums may compromise their acceptability by patients. This study was, therefore, designed to develop 2 and 4 mg nicotine chewing gums of pleasant taste, which satisfy the consumers the most. Nicotine, sugar, liquid glucose, glycerin, different sweetening and taste-masking agents, and a flavoring agent were added to the gum bases at appropriate temperature. The medicated gums were cut into pieces of suitable size and coated by acacia aqueous solution (2% w/v), sugar dusting, followed by acacia-sugar-calcium carbonate until a smooth surface was produced. The gums' weight variation and content uniformity were determined. The release of nicotine was studied in pH 6.8 phosphate buffer using a mastication device which simulated the mastication of chewing gum in human. The Latin Square design was used for the evaluation of organoleptic characteristics of the formulations at different stages of development. Most formulations released 79-83% of their nicotine content within 20 min. Nicotine-containing sugar-coated gums in which aspartame as sweetener and cherry and eucalyptus as flavoring agents were incorporated (i.e. formulations F(19-SC) and F(20-SC), respectively) had optimal chewing hardness, adhering to teeth, and plumpness characteristics, as well as the most pleasant taste and highest acceptability to smokers. Taste enhancement of nicotine gums was achieved where formulations comprised aspartame as the sweetener and cherry and eucalyptus as the flavoring agents. Nicotine gums of pleasant taste may, therefore, be used as NRT to assist smokers quit smoking.

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

DEFF Research Database (Denmark)

Christensen, Mark Holm; Ishibashi, Masaru; Nielsen, Michael Linnemann

2014-01-01

The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved...... in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7–P15), nicotine induced larger...... intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15–P34). Nicotine increased neuronal firing of cholinergic cells...

Ethanol-nicotine interactions in long-sleep and short-sleep mice.

Science.gov (United States)

de Fiebre, C M; Marks, M J; Collins, A C

1990-01-01

The possibility that common genetic factors regulate initial sensitivities to ethanol and nicotine as well as the development of cross-tolerance between these agents was explored using the long-sleep (LS) and short-sleep (SS) mice. The LS mice proved to be more sensitive to an acute challenge with nicotine than were the SS mice. Segregation analysis (F1, F2, backcross) indicated that ethanol sensitivity and nicotine sensitivity segregate together. Acute pretreatment with nicotine did not significantly affect sensitivity to ethanol, but ethanol pretreatment altered nicotine responsiveness. The LS mice develop more tolerance to nicotine and ethanol than do the SS and they also develop more cross-tolerance. These genetically determined differences in initial sensitivities, and tolerance and cross-tolerance development are not readily explained by differences in brain nicotinic receptor numbers.

Ethanol-nicotine interactions in long-sleep and short-sleep mice

Energy Technology Data Exchange (ETDEWEB)

de Fiebre, C.M.; Marks, M.J.; Collins, A.C. (Univ. of Colorado, Boulder (USA))

1990-05-01

The possibility that common genetic factors regulate initial sensitivities to ethanol and nicotine as well as the development of cross-tolerance between these agents was explored using the long-sleep (LS) and short-sleep (SS) mice. The LS mice proved to be more sensitive to an acute challenge with nicotine than were the SS mice. Segregation analysis (F1, F2, backcross) indicated that ethanol sensitivity and nicotine sensitivity segregate together. Acute pretreatment with nicotine did not significantly affect sensitivity to ethanol, but ethanol pretreatment altered nicotine responsiveness. The LS mice develop more tolerance to nicotine and ethanol than do the SS and they also develop more cross-tolerance. These genetically determined differences in initial sensitivities, and tolerance and cross-tolerance development are not readily explained by differences in brain nicotinic receptor numbers.

Sex differences in nicotine intravenous self-administration: A meta-analytic review.

Science.gov (United States)

Flores, Rodolfo J; Uribe, Kevin P; Swalve, Natashia; O'Dell, Laura E

2017-11-21

This report reflects a meta-analysis that systematically reviewed the literature on intravenous self-administration (IVSA) of nicotine in female and male rats. The goal was to determine if sex differences in nicotine IVSA exist, estimate the magnitude of the effect, and identify potential moderators of the relationship between sex differences and nicotine consumption. Extensive search procedures identified 20 studies that met the inclusion criteria of employing both female and male rats in nicotine IVSA procedures. The meta-analysis was conducted on effect size values that were calculated from mean total intake or nicotine deliveries using the Hedges' unbiased g u statistic. A random effects analysis revealed that overall females self-administered more nicotine than males (weighted g u =0.18, 95% CI [0.003, 0.34]). Subsequent moderator variable analyses revealed that certain procedural conditions influenced the magnitude of sex differences in nicotine IVSA. Specifically, higher reinforcement requirements (>FR1) and extended-access sessions (23h) were associated with greater nicotine IVSA in females versus males. Females also displayed higher nicotine intake than males when the experiment included a light cue that signaled nicotine delivery. Sex differences were not influenced by the diurnal phase of testing, dose of nicotine, or prior operant training. Overall, the results revealed that female rats display higher levels of nicotine IVSA than males, suggesting that the strong reinforcing effects of nicotine promote tobacco use in women. Copyright © 2017 Elsevier Inc. All rights reserved.

Nicotine facilitates nicotinic acetylcholine receptor targeting to mitochondria but makes them less susceptible to selective ligands.

Science.gov (United States)

Uspenska, Kateryna; Lykhmus, Olena; Gergalova, Galyna; Chernyshov, Volodymyr; Arias, Hugo R; Komisarenko, Sergiy; Skok, Maryna

2017-08-24

Several nicotinic acetylcholine receptor (nAChR) subtypes are expressed in mitochondria to regulate the internal pathway of apoptosis in ion channel-independent manner. However, the mechanisms of nAChR activation in mitochondria and targeting to mitochondria are still unknown. Nicotine has been shown to favor nAChR pentamer assembly, folding, and maturation on the way of biosynthesis. The idea of the present work was to determine whether nicotine affects the content, glycosylation, and function of mitochondrial nAChRs. Experiments were performed in isolated liver mitochondria from mice, that either consumed or not nicotine with the drinking water (200μL/L) for 7days. Mitochondria detergent lysates were studied by sandwich or lectin ELISA for the presence and carbohydrate composition of different nAChR subunits. Intact mitochondria were examined by flow cytometry for the binding of fluorescently labeled α-cobratoxin and were tested in functional assay of cytochrome c release under the effect of either Ca 2+ or wortmannin in the presence or absence of nAChR-selective ligands, including PNU-282987 (1nM), dihydro-β-erythroidine (DhβE, 1μM), PNU-120596 (0.3, 3, or 10μM) and desformylflustrabromine hydrochloride (dFBr, 0.001, 0.3, or 1μM). It was found that nicotine consumption increased the ratio of mitochondrial vs non-mitochondrial nAChRs in the liver, enhanced fucosylation of mitochondrial nAChRs, but prevented the binding of α-cobratoxin and the cytochrome c release-attenuating effects of nAChR-specific agonists, antagonists, or positive allosteric modulators. It is concluded that nicotine consumption in vivo favors nAChR glycosylation and trafficking to mitochondria but makes them less susceptible to the effects of specific ligands. Copyright © 2017 Elsevier B.V. All rights reserved.

Tropane and nicotine alkaloid biosynthesis-novel approaches towards biotechnological production of plant-derived pharmaceuticals.

Science.gov (United States)

Oksman-Caldentey, Kirsi-Marja

2007-08-01

Many plants belonging to the Solanaceae family have been used as a source of pharmaceuticals for centuries because of their active principles, tropane and nicotine alkaloids. Tropane alkaloids, atropine, hyoscyamine and scopolamine, are among the oldest drugs in medicine. On the other hand nicotine, the addictive agent in tobacco, has only recently gained attention as a backbone for novel potential alkaloids to be used for certain neurological diseases. The biotechnological production of alkaloids utilizing plant cells as hosts would be an attractive option. However, to date very little success in this field has been gained because of the lack of understanding how these compounds are synthesized in a plant cell. Metabolic engineering attempts have already shown that when the rate-limiting steps of the biosynthetic pathway are completely known and the respective genes cloned, the exact regulation towards desired medicinal products will be possible in the near future. The new functional genomics tools, which combine transcriptome and metabolome data, will create a platform to better understand a whole system and to engineer the complex plant biosynthetic pathways. With the help of this technology, it is not only possible to produce known plant metabolites more effectively but also to make arrays of new compounds in plants and cell cultures.

Global actions of nicotine on the striatal microcircuit.

Science.gov (United States)

Plata, Víctor; Duhne, Mariana; Pérez-Ortega, Jesús; Hernández-Martinez, Ricardo; Rueda-Orozco, Pavel; Galarraga, Elvira; Drucker-Colín, René; Bargas, José

2013-01-01

what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

Impact of a smoking ban in hospitality venues on second hand smoke exposure: a comparison of exposure assessment methods.

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Rajkumar, Sarah; Huynh, Cong Khanh; Bauer, Georg F; Hoffmann, Susanne; Röösli, Martin

2013-06-04

In May 2010, Switzerland introduced a heterogeneous smoking ban in the hospitality sector. While the law leaves room for exceptions in some cantons, it is comprehensive in others. This longitudinal study uses different measurement methods to examine airborne nicotine levels in hospitality venues and the level of personal exposure of non-smoking hospitality workers before and after implementation of the law. Personal exposure to second hand smoke (SHS) was measured by three different methods. We compared a passive sampler called MoNIC (Monitor of NICotine) badge, to salivary cotinine and nicotine concentration as well as questionnaire data. Badges allowed the number of passively smoked cigarettes to be estimated. They were placed at the venues as well as distributed to the participants for personal measurements. To assess personal exposure at work, a time-weighted average of the workplace badge measurements was calculated. Prior to the ban, smoke-exposed hospitality venues yielded a mean badge value of 4.48 (95%-CI: 3.7 to 5.25; n = 214) cigarette equivalents/day. At follow-up, measurements in venues that had implemented a smoking ban significantly declined to an average of 0.31 (0.17 to 0.45; n = 37) (p = 0.001). Personal badge measurements also significantly decreased from an average of 2.18 (1.31-3.05 n = 53) to 0.25 (0.13-0.36; n = 41) (p = 0.001). Spearman rank correlations between badge exposure measures and salivary measures were small to moderate (0.3 at maximum). Nicotine levels significantly decreased in all types of hospitality venues after implementation of the smoking ban. In-depth analyses demonstrated that a time-weighted average of the workplace badge measurements represented typical personal SHS exposure at work more reliably than personal exposure measures such as salivary cotinine and nicotine.

Adsorption of nicotine on different zeolite types, from aqueous solutions

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Stošić Dušan K.

2007-01-01

Full Text Available The plant alkaloid, nicotine, is a strongly toxic heterocyclic compound: the lethal dose for an adult human being (40-60 mg is importantly lower in comparison with the other known poisons such as arsenic or strychni­ne. Cigarettes represent "the most toxic and addictive form of nicotine". Besides the negative effects of nicotine on public health produced by self-administration, recently another potentially very dangerous effect has been recognized: because of its miscibility with water, nicotine can be found in industrial wastewaters, and consequently, in groundwater. Therefore, the problem of nicotine removal from aqueous solutions has became an interesting topic. In this work, the removal of nicotine has been probed by adsorption on solid materials. Adsorption of nicotine on different zeolites (clinoptilolite, ZSM-5 and β zeolite and on activated carbon was investigated from aqueous solutions, at 298 K. The obtained results are presented as adsorption isotherms: the amount of adsorbed nicotine as a function of equilibrium concentration. These data were obtained from the residual amount of nicotine in the aqueous phase, by the use of UV spectroscopy. The highest amounts of adsorbed nicotine was found for activated carbon and p zeolite (~ mmol·g-1. The attempt to modify the adsorption properties of ZSM-5 zeolite has been also done: ZSM-5 was modified by ion-exchange with VIII group metal (Cu2+ and Fe3+. In addition, the adsorption of nicotine on ZSM-5 zeolite with different Si/Al ratios has been done. It has been noticed that ion-exchange did not improve the adsorption possibilities, while the adsorption was importantly lower in the case of higher silicon content in ZMS-5 structure. 13C NMR spectra were collected for suspensions formed of solid adsorbent and aqueous solution of nicotine; in this way, the part of nicotine molecule which is most probably connected with the adsorbent was recognized.

Nicotine inhibits potassium currents in Aplysia bag cell neurons

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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

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges
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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.
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T100. NICOTINE USE IMPACTS NEGATIVE SYMPTOMS SEVERITY IN SCHIZOPHRENIA

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Oliveira, Hianna; Coutinho, Luccas; Higuchi, Cinthia; Noto, Cristiano; Bressan, Rodrigo; Gadelha, Ary

2018-01-01

Abstract Background Nicotine use is higher among patients with schizophrenia (50–98%) than in general population (25–30%). This association can reflect a non-specific liability to substance use or specific effects of tobacco on symptoms severity or side effects. Studies about nicotine use and schizophrenia symptoms dimensions are controversial. Some of them showed a relation between severe nicotine use and higher positive symptoms and others presented a correlation between lower negative symptoms and nicotine use. That is why we aimed to verify whether nicotine use is associated with symptoms dimensions in patients with schizophrenia. Methods Two hundred and seven outpatients were enrolled from the Programa de Esquizofrenia da Universidade Federal de São Paulo (PROESQ/UNIFESP). Schizophrenia diagnosis was confirmed by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Dimensional psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS) and Fagerstrom Test for Nicotine Dependence. The PANSS items were grouped in five dimensions: positive, negative, disorganized/cognitive, mood/depression and excitement/hostility. The total score of Fagerstrom Test for Nicotine Dependence was the index used for severity in nicotine dependence. We used Wilcoxon-mann- whitney test to compare the means of PANSS dimensions between nicotine users versus non nicotine use. Results The patients mean age was 36.75 (SD 10.648), 69.1% were male, 48.3% reported lifetime tobacco use and 34.3% reported current tobacco use. Lower scores on negative dimension were associated with nicotine use (W = 5642.5, p-value = 0.046, effect size = 0.446). All p-values were corrected by Bonferroni test. Tests that evaluated the relationship between nicotine use and the total PANSS score or other dimensions were not statistically significant. Discussion This study shows that nicotine use impacts negative symptoms of schizophrenia. Increase in hepatic metabolism leading

Emerging nicotine delivery products. Implications for public health.

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Benowitz, Neal L

2014-02-01

The idea of clean nicotine delivery systems that would satisfy nicotine craving and promote smoking cessation has been considered as a possible public health tool for many years. Nicotine medications have been useful for smoking cessation but have not found widespread popularity among smokers, perhaps because of slow nicotine delivery and other sensory characteristics that differ from cigarettes. Traditional smokeless tobacco delivers as much nicotine as cigarettes and has been advocated for harm reduction but contains carcinogenic nitrosamines and has not been proven to promote cessation. Furthermore, there is concern that dual use of smokeless tobacco and cigarettes may inhibit quitting smoking. Newer oral dissolvable tobacco products contain lower levels of toxicants than other smokeless tobacco but also deliver much less nicotine and have not been popular with consumers. Electronic cigarettes that aerosolize nicotine without generating toxic tobacco combustion products have become quite popular and hold promise as a way to attract smokers away from cigarettes, although efficacy in promoting smoking cessation has not yet been demonstrated. There are concerns about safety of long-term use, and there is evidence that youth, including nonsmokers, are taking up e-cigarette use. E-cigarettes are marketed for use when one cannot smoke conventional cigarettes, and such use might result in more persistent cigarette smoking. Although their benefits and risks are being vigorously debated, e-cigarettes or other clean nicotine delivery devices could play an important role as an adjunct to a U.S. Food and Drug Administration regulatory intervention to make cigarettes less addictive and in this context could contribute to the end of cigarette smoking and smoking-induced disease.

Nicotine affects protein complex rearrangement in Caenorhabditis elegans cells.

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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.

E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices.

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Steinberg, Michael B; Zimmermann, Mia Hanos; Delnevo, Cristine D; Lewis, M Jane; Shukla, Parth; Coups, Elliot J; Foulds, Jonathan

2014-11-01

Novel nicotine delivery products, such as electronic cigarettes (e-cigarettes), have dramatically grown in popularity despite limited data on safety and benefit. In contrast, the similar U.S. Food and Drug Administration (FDA)-approved nicotine inhaler is rarely utilized by smokers. Understanding this paradox could be helpful to determine the potential for e-cigarettes as an alternative to tobacco smoking. To compare the e-cigarette with the nicotine inhaler in terms of perceived benefits, harms, appeal, and role in assisting with smoking cessation. A cross-over trial was conducted from 2012 to 2013 PARTICIPANTS/INTERVENTIONS: Forty-one current smokers age 18 and older used the e-cigarette and nicotine inhaler each for 3 days, in random order, with a washout period in between. Thirty-eight participants provided data on product use, perceptions, and experiences. The Modified Cigarette Evaluation Questionnaire (mCEQ) measured satisfaction, reward, and aversion. Subjects were also asked about each product's helpfulness, similarity to cigarettes, acceptability, image, and effectiveness in quitting smoking. Cigarette use was also recorded during the product-use periods. The e-cigarette had a higher total satisfaction score (13.9 vs. 6.8 [p e-cigarette received higher ratings for helpfulness, acceptability, and "coolness." More subjects would use the e-cigarette to make a quit attempt (76 %) than the inhaler (24 %) (p e-cigarette vs. 10 % (4/38) using the inhaler (p = 0.18). The e-cigarette was more acceptable, provided more satisfaction, and had higher perceived benefit than the inhaler during this trial. E-cigarettes have the potential to be important nicotine delivery products owing to their high acceptance and perceived benefit, but more data are needed to evaluate their actual efficacy and safety. Providers should be aware of these issues, as patients will increasingly inquire about them.

Electronic cigarettes are a source of thirdhand exposure to nicotine.

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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 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.