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Sample records for nicotine primarily suppresses

  1. Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation

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    Yan, You-e [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Liu, Lian [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Department of Pharmacology, Medical School of Yangtze University, Jingzhou 434000 (China); Wang, Jian-fei; Liu, Fang; Li, Xiao-hai; Qin, Hai-quan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

    2014-06-15

    This study aimed to investigate the suppressive effect of nicotine on fetal adrenal steroidogenesis and to explore the potential role of epigenetic modification of steroidogenic factor-1 (SF-1) transcriptional activity in this process. Nicotine was intragastrically administered to pregnant rats and NCI-H295A cells were treated with nicotine or trichostatin A (TSA). The pathomorphology of fetal adrenals, steroid hormone levels, the expression of SF-1 and its target genes, and histone deacetylase (HDAC) mRNA were analyzed. Histone modification and DNA methylation of the SF-1 promoter region were assessed using chromatin immunoprecipitation (ChIP) and bisulfite sequencing PCR. The interaction between SF1 and its target genes was observed. Prenatal nicotinic exposure decreased fetal body weight, increased the IUGR rate and caused detrimental changes in fetal adrenal. In addition, the levels of corticosterone, the expression of SF-1 and its target genes were decreased while HDAC2 expression was enhanced. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region. Furthermore, in nicotine-treated NCI-H295A cells, lower levels of steroidogenic synthesis, lower expression of SF-1 and its target genes were observed while the expression of HDACs was enhanced. The interaction between SF1 and StAR decreased with nicotine treatment. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels, and addition of TSA reversed the inhibition of nicotine-mediated SF-1 and its partial target genes. Thus, nicotine-mediated reduction of SF-1 expression resulted in an inhibitory effect on the expression of its target genes and steroid production via histone deacetylation. - Highlights: • Prenatal nicotine-exposed suppresses fetal adrenal steroidogenesis. • Nicotine-supressed fetal adrenal steroidogenesis is related to SF-1 deacetylation. • Prenatal nicotinic exposure decreased

  2. Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation

    International Nuclear Information System (INIS)

    Yan, You-e; Liu, Lian; Wang, Jian-fei; Liu, Fang; Li, Xiao-hai; Qin, Hai-quan; Wang, Hui

    2014-01-01

    This study aimed to investigate the suppressive effect of nicotine on fetal adrenal steroidogenesis and to explore the potential role of epigenetic modification of steroidogenic factor-1 (SF-1) transcriptional activity in this process. Nicotine was intragastrically administered to pregnant rats and NCI-H295A cells were treated with nicotine or trichostatin A (TSA). The pathomorphology of fetal adrenals, steroid hormone levels, the expression of SF-1 and its target genes, and histone deacetylase (HDAC) mRNA were analyzed. Histone modification and DNA methylation of the SF-1 promoter region were assessed using chromatin immunoprecipitation (ChIP) and bisulfite sequencing PCR. The interaction between SF1 and its target genes was observed. Prenatal nicotinic exposure decreased fetal body weight, increased the IUGR rate and caused detrimental changes in fetal adrenal. In addition, the levels of corticosterone, the expression of SF-1 and its target genes were decreased while HDAC2 expression was enhanced. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region. Furthermore, in nicotine-treated NCI-H295A cells, lower levels of steroidogenic synthesis, lower expression of SF-1 and its target genes were observed while the expression of HDACs was enhanced. The interaction between SF1 and StAR decreased with nicotine treatment. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels, and addition of TSA reversed the inhibition of nicotine-mediated SF-1 and its partial target genes. Thus, nicotine-mediated reduction of SF-1 expression resulted in an inhibitory effect on the expression of its target genes and steroid production via histone deacetylation. - Highlights: • Prenatal nicotine-exposed suppresses fetal adrenal steroidogenesis. • Nicotine-supressed fetal adrenal steroidogenesis is related to SF-1 deacetylation. • Prenatal nicotinic exposure decreased

  3. Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors.

    Science.gov (United States)

    Melis, Miriam; Pillolla, Giuliano; Luchicchi, Antonio; Muntoni, Anna Lisa; Yasar, Sevil; Goldberg, Steven R; Pistis, Marco

    2008-12-17

    Nicotine stimulates the activity of mesolimbic dopamine neurons, which is believed to mediate the rewarding and addictive properties of tobacco use. Accumulating evidence suggests that the endocannabinoid system might play a major role in neuronal mechanisms underlying the rewarding properties of drugs of abuse, including nicotine. Here, we investigated the modulation of nicotine effects by the endocannabinoid system on dopamine neurons in the ventral tegmental area with electrophysiological techniques in vivo and in vitro. We discovered that pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme that catabolizes fatty acid ethanolamides, among which the endocannabinoid anandamide (AEA) is the best known, suppressed nicotine-induced excitation of dopamine cells. Importantly, this effect was mimicked by the administration of the FAAH substrates oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), but not methanandamide, the hydrolysis resistant analog of AEA. OEA and PEA are naturally occurring lipid signaling molecules structurally related to AEA, but devoid of affinity for cannabinoid receptors. They blocked the effects of nicotine by activation of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor transcription factor involved in several aspects of lipid metabolism and energy balance. Activation of PPAR-alpha triggered a nongenomic stimulation of tyrosine kinases, which might lead to phosphorylation and negative regulation of neuronal nicotinic acetylcholine receptors. These data indicate for the first time that the anorexic lipids OEA and PEA possess neuromodulatory properties as endogenous ligands of PPAR-alpha in the brain and provide a potential new target for the treatment of nicotine addiction.

  4. Ah receptor mediated suppression of the antibody response in mice is primarily dependent on the Ah phenotype of lymphoid tissue

    International Nuclear Information System (INIS)

    Silkworth, J.B.; Antrim, L.A.; Sack, G.

    1986-01-01

    Halogenated aromatic hydrocarbons act through the aromatic hydrocarbon (Ah) receptor in mice to produce a series of toxic effects of the immune system. The receptor protein is a product of the Ah gene locus. Ah responsive (Ahb/Ahb) mice express a high affinity receptor in both lymphoid and nonlymphoid tissues whereas nonresponsive Ahd/Ahd mice express a poor affinity receptor. To determine the role of the Ah receptor of lymphoid tissue relative to that of nonlymphoid tissue in the induction of immune impairment, bone marrow was used to reconstitute lethally irradiated mice of the same or opposite Ah phenotype. All mice were given 3,3',4,4'-tetrachlorobiphenyl (35 and 350 mumol/kg) ip 2 days before immunization with sheep erythrocytes (SRBC). The immune response to this T dependent antigen and organ weights were determined 5 or 7 days later in normal or chimeric mice, respectively. Monoclonal Lyt 1.1 and Lyt 1.2 antibodies were used to establish the origin of the cells which repopulated the chimeric thymuses. The immune responses of both BALB/cBy (Ahb/Ahb) and the BALB/cBy X DBA/2 hybrid, CByD2F1 (Ahb/Ahd), were significantly suppressed but DBA/2 mice were unaffected. The immune responses of chimeric BALB/cBy----BALB/cBy and BALB/cBy----DBA/2 (donor----recipient) mice were also significantly suppressed and thymic atrophy was observed in both cases. The serum anti-SRBC antibody titers of DBA/2----BALB/cBy chimeras were also significantly decreased although not to the same extent as in BALB/cBy----DBA/2 mice. Chimeric DBA/2----DBA/2 mice were not affected. These results indicate that the sensitivity to Ah receptor mediated suppression of the antibody response is primarily determined by the Ah phenotype of the lymphoid tissue

  5. Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress.

    Science.gov (United States)

    Cai, Yanxue; Zhang, Xianwen; Zhou, Xiaoshuang; Wu, Xiaoli; Li, Yanhui; Yao, Jianhua; Bai, Jie

    2017-03-01

    Parkinson's disease (PD) is a neurodegenerative disease. Nicotine has been reported to have the role in preventing Parkinson's disease. However, its mechanism is still unclear. In present study we found that nicotine suppressed 1-methyl-4-phenylpyridinium ion(MPP + ) toxicity in PC12 cells by MTT assay. The expression of thioredoxin-1(Trx-1) was decreased by MPP + , which was restored by nicotine. The nicotine suppressed expressions of Glucose-regulated protein 78(GRP78/Bip) and C/EBP homologous protein (CHOP) induced by MPP + . The methyllycaconitine (MLA), the inhibitor of α7nAChR and LY294002, the inhibitor of phosphatidylinositol 3-kinase (PI3K) blocked the suppressions of above molecules, respectively. Consistently, pretreatment with nicotine ameliorated the motor ability, restored the declines of Trx-1 and tyrosine hydroxylase (TH), and suppressed the expressions of Bip and CHOP induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Our results suggest that nicotine plays role in resisting MPP + /MPTP neurotoxicity through activating the α7nAChR/PI3K/Trx-1 pathway and suppressing ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Luan, Yan; Deqin, Yang

    2017-08-01

    Objective To explore the impact of nicotine on proliferation and osteogenic capability of periodontal ligament stem cells (PDLSCs), and the role of Toll-like receptor 4 (TLR4) in nicotine, suppressing the osteogenic capability of PDLSCs. Methods PDLSCs were cultured in vitro, and the flow cytometer was used to identify the surface antigen markers of PDLSCs. WST-1 was used to detect the proliferation ability of PDLSCs, which were stimulated by different concentrations of nicotine. Alizarin red staining was used to observe the formation of mineralized nodules after PDLSCs stimulation with different concentrations of nicotine. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to detect the change in osteogenic potential of PDLSCs stimulated by nicotine, after TAK-242, and with the inhibitor of TLR4. Results PDLSCs expressed mesenchymal stem cell-associated markers CD90 and CD105. When the concentration of nicotine was 10⁻⁴ mol·L⁻¹, the PDLSC proliferation could be suppressed after 3 d compared with the control group (Pnicotine suppressed the PDLSCs (PNicotine suppresses the proliferation and osteogenic capability of PDLSCs, which may be regulated by TLR4.

  7. Nicotine-mediated suppression of the retinoic acid metabolizing enzyme CYP26A1 limits the oncogenic potential of breast cancer.

    Science.gov (United States)

    Osanai, Makoto; Lee, Gang-Hong

    2011-06-01

    Tobacco smoke influences cancer development in tissues that are not directly exposed, and epidemiological studies have indicated that smoking women might experience decreased risk of breast cancer as a result of antiestrogenic effects. However, it remains to be clarified whether nicotine, one of the major addictive and best-investigated constituents of tobacco smoke, has any effect on breast cancer. Our recent work demonstrated that the retinoic acid metabolizing enzyme CYP26A1 enhances oncogenic and cell survival properties of breast carcinoma cells, implying a role as an oncogene. Here, we present evidence that nicotine significantly suppresses constitutive expression of CYP26A1, and that cells treated with nicotine exhibit enhanced sensitivity to apoptosis. In addition, nicotine may inhibit anchorage independent growth, cellular invasiveness and motility. These data show that nicotine can limit CYP26A1-mediated oncogenic characteristics, and suggest mechanisms by which nicotine might inhibit breast cancer development. © 2011 Japanese Cancer Association.

  8. ANTAGONISM OF PROGESTERONE RECEPTOR SUPPRESSES CAROTID BODY RESPONSES TO HYPOXIA AND NICOTINE IN RAT PUPS

    Science.gov (United States)

    JOSEPH, V.; NIANE, L. M.; BAIRAM, A.

    2013-01-01

    We tested the hypothesis that antagonism of progesterone receptor (PR) in newborn rats alters carotid body and respiratory responses to hypoxia and nicotinic receptor agonists. Rats were treated with the PR antagonist mifepristone (daily oral gavage 40 μg/g/d) or vehicle between post-natal days 3 and 15. In 11–14-day-old rats, we used in vitro carotid body/carotid sinus nerve preparation and whole body plethysmography to assess the carotid body and ventilatory responses to hypoxia (65 mmHg in vitro, 10% O2 in vivo) and to nicotinic receptor agonists (as an excitatory modulator of carotid body activity—nicotine 100 μM for in vitro studies, and epibatidine 5 μg/kg, i.p., which mainly acts on peripheral nicotinic receptors, for in vivo studies). The carotid body responses to hypoxia and nicotine were drastically reduced by mifepristone. Compared with vehicle, mifepristone-treated rats had a reduced body weight. The ventilatory response to epibatidine was attenuated; however, the hypoxic ventilatory response was similar between vehicle and mifepristone-treated pups. Immunohistochemical staining revealed that mifepristone treatment did not change carotid body morphology. We conclude that PR activity is a critical factor ensuring proper carotid body function in newborn rats. PMID:22326965

  9. ANTAGONISM OF PROGESTERONE RECEPTOR SUPPRESSES CAROTID BODY RESPONSES TO HYPOXIA AND NICOTINE IN RAT PUPS

    OpenAIRE

    JOSEPH, V.; NIANE, L. M.; BAIRAM, A.

    2012-01-01

    We tested the hypothesis that antagonism of progesterone receptor (PR) in newborn rats alters carotid body and respiratory responses to hypoxia and nicotinic receptor agonists. Rats were treated with the PR antagonist mifepristone (daily oral gavage 40 μg/g/d) or vehicle between post-natal days 3 and 15. In 11–14-day-old rats, we used in vitro carotid body/carotid sinus nerve preparation and whole body plethysmography to assess the carotid body and ventilatory responses to hypoxia (65 mmHg in...

  10. Work Stress and Depressive Symptoms in Fishermen With a Smoking Habit: A Mediator Role of Nicotine Dependence and Possible Moderator Role of Expressive Suppression and Cognitive Reappraisal.

    Science.gov (United States)

    Jiang, Hongjuan; Li, Sailan; Yang, Juan

    2018-01-01

    This study examined pathways of influence between work stress, depressive symptoms, nicotine dependence, expressive suppression, and cognitive reappraisal in fishermen with smoking habits in Qionghai, Hainan province, China (N = 1068). These fishermen responded to multiple assessments a week before leaving on a deep-sea fishing trip, including a Mental Stressor Investigation Questionnaire (MSIQ), the Center for Epidemiological Studies Depression Scale (CES-D), the Russell Reason for Smoking Questionnaire (RRSQ), and an Emotion Regulation Questionnaire (ERQ). Structural equation modeling (SEM) analyses of the collected data in Mplus 7 showed that work stress and nicotine dependence were independent predictors of depressive symptoms. The relationship between work stress and depressive symptoms was found to be partially mediated by nicotine dependence and be moderated by cognitive reappraisal. The evidence suggests it advantageous to examine the need of work stress, nicotine dependence, and cognitive reappraisal when attempting to understand depressive symptoms in fishermen with a smoking habit. These findings suggest that improving nicotine dependence through work stress management and training in cognitive reappraisal could be utilized as effective modalities for improving depressive symptoms.

  11. Impaired compensation to femoral artery ligation in diet-induced obese mice is primarily mediated via suppression of collateral growth by Nox2 and p47phox.

    Science.gov (United States)

    DiStasi, Matthew R; Mund, Julie A; Bohlen, H Glenn; Miller, Steven J; Ingram, David A; Dalsing, Michael C; Unthank, Joseph L

    2015-10-01

    The present study was undertaken to establish the role of NADPH oxidase (Nox) in impaired vascular compensation to arterial occlusion that occurs in the presence of risk factors associated with oxidative stress. Diet-induced obese (DIO) mice characterized by multiple comorbidities including diabetes and hyperlipidemia were used as a preclinical model. Arterial occlusion was induced by distal femoral artery ligation in lean and DIO mice. Proximal collateral arteries were identified as the site of major (∼70%) vascular resistance to calf perfusion by distal arterial pressures, which decreased from ∼80 to ∼30 mmHg with ligation in both lean and DIO mice. Two weeks after ligation, significant vascular compensation occurred in lean but not DIO mice as evidenced by increased perfusion (147 ± 48% vs. 49 ± 29%) and collateral diameter (151 ± 30% vs. 44 ± 17%). Vascular mRNA expression of p22(phox), Nox2, Nox4, and p47(phox) were all increased in DIO mice. Treatment of DIO mice with either apocynin or Nox2ds-tat or with whole body ablation of either Nox2 or p47(phox) ameliorated the impairment in both collateral growth and hindlimb perfusion. Multiparametric flow cytometry analysis demonstrated elevated levels of circulating monocytes in DIO mice without impaired mobilization and demargination after femoral artery ligation. These results establish collateral resistance as the major limitation to calf perfusion in this preclinical model, demonstrate than monocyte mobilization and demarginatin is not suppressed, implicate Nox2-p47(phox) interactions in the impairment of vascular compensation to arterial occlusion in DIO mice, and suggest that selective Nox component suppression/inhibition may be effective as either primary or adjuvant therapy for claudicants. Copyright © 2015 the American Physiological Society.

  12. 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.

  13. 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 ...

  14. Toward a comprehensive long term nicotine policy.

    Science.gov (United States)

    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.

  15. Validation of a LC-MS/MS method for quantifying urinary nicotine, six nicotine metabolites and the minor tobacco alkaloids--anatabine and anabasine--in smokers' urine.

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    James E McGuffey

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

  16. Spinal activation of alpha7-nicotinic acetylcholine receptor attenuates posttraumatic stress disorder-related chronic pain via suppression of glial activation.

    Science.gov (United States)

    Sun, Rao; Zhang, Wei; Bo, Jinhua; Zhang, Zuoxia; Lei, Yishan; Huo, Wenwen; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

    2017-03-06

    The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain. The experiments were conducted in a rat model of single prolonged stress (SPS), an established model of PTSD-pain comorbidity. We found that SPS exposure produced persistent mechanical allodynia. Immunohistochemical and enzyme-linked immuno sorbent assay analysis showed that SPS also induced elevated activation of glia cells (including microglia and astrocytes) and accumulation of pro-inflammatory cytokines in spinal cord. In another experiment, we found that intrathecal injection of PHA-543613, a selective α7 nAchR agonist, attenuated the SPS-evoked allodynia in a dose dependent manner. However, this anti-hyperalgesic effect was blocked by pretreatment with methyllycaconitine (MLA), a selective α7 nAchR antagonist. Further analyses showed that PHA-543613 suppressed SPS-induced spinal glial activation and SPS-elevated spinal pro-inflammatory cytokines, and these were abolished by MLA. Taken together, the present study showed that spinal activation of α7 nAChR by PHA-543613 attenuated mechanical allodynia induced by PTSD-like stress, and the suppression of spinal glial activation may underlie this anti-hyperalgesic effect. Our study demonstrated the therapeutic potential of targeting α7 nAChR in the treatment of PTSD-related chronic pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. 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.

  18. 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.

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

    Science.gov (United States)

    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.

  20. 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 ...

  1. Central infusion of leptin improves insulin resistance and suppresses beta-cell function, but not beta-cell mass, primarily through the sympathetic nervous system in a type 2 diabetic rat model.

    Science.gov (United States)

    Park, Sunmin; Ahn, Il Sung; Kim, Da Sol

    2010-06-05

    We investigated whether hypothalamic leptin alters beta-cell function and mass directly via the sympathetic nervous system (SNS) or indirectly as the result of altered insulin resistant states. The 90% pancreatectomized male Sprague Dawley rats had sympathectomy into the pancreas by applying phenol into the descending aorta (SNSX) or its sham operation (Sham). Each group was divided into two sections, receiving either leptin at 300ng/kgbw/h or artificial cerebrospinal fluid (aCSF) via intracerebroventricular (ICV) infusion for 3h as a short-term study. After finishing the infusion study, ICV leptin (3mug/kg bw/day) or ICV aCSF (control) was infused in rats fed 30 energy % fat diets by osmotic pump for 4weeks. At the end of the long-term study, glucose-stimulated insulin secretion and islet morphometry were analyzed. Acute ICV leptin administration in Sham rats, but not in SNSX rats, suppressed the first- and second-phase insulin secretion at hyperglycemic clamp by about 48% compared to the control. Regardless of SNSX, the 4-week administration of ICV leptin improved glucose tolerance during oral glucose tolerance tests and insulin sensitivity at hyperglycemic clamp, compared to the control, while it suppressed second-phase insulin secretion in Sham rats but not in SNSX rats. However, the pancreatic beta-cell area and mass were not affected by leptin and SNSX, though ICV leptin decreased individual beta-cell size and concomitantly increased beta-cell apoptosis in Sham rats. Leptin directly decreases insulin secretion capacity mainly through the activation of SNS without modulating pancreatic beta-cell mass.

  2. Nicotine stimulates pancreatic cancer xenografts by systemic increase in stress neurotransmitters and suppression of the inhibitory neurotransmitter gamma-aminobutyric acid.

    Science.gov (United States)

    Al-Wadei, Hussein A N; Plummer, Howard K; Schuller, Hildegard M

    2009-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality in Western countries. We have shown previously that four representative human PDAC cell lines were regulated by beta-adrenoreceptors via cyclic adenosine 3',5'-monophosphate (cAMP)-dependent signaling. In the current study, we have tested the hypothesis that nicotine stimulates the growth of PDAC xenografts in nude mice by increasing the systemic levels of the stress neurotransmitters adrenaline and noradrenaline, which are the physiological agonists for beta-adrenoreceptors and that inhibition by gamma-aminobutyric acid (GABA) of the adenylyl cyclase-dependent pathway downstream of adrenoreceptors blocks this effect. The size of xenografts from PDAC cell line Panc-1 was determined 30 days after inoculation of the cancer cells. Stress neurotransmitters in serum as well as cAMP in the cellular fraction of blood and in tumor tissue were assessed by immunoassays. Levels of GABA, its synthesizing enzymes GAD65 and GAD67 and beta-adrenergic signaling proteins in the tumor tissue were determined by western blotting. Nicotine significantly increased the systemic levels of adrenaline, noradrenaline and cAMP while increasing xenograft size and protein levels of cAMP, cyclic AMP response element-binding protein and p-extracellular signal-regulated kinase 1/2 in the tumor tissue. Nicotine additionally reduced the protein levels of both GAD isozymes and GABA in tumor tissue. Treatment with GABA abolished these responses to nicotine and blocked the development of xenografts in mice not exposed to nicotine. These findings suggest that the development and progression of PDAC is subject to significant modulation by stimulatory stress neurotransmitters and inhibitory GABA and that treatment with GABA may be useful for marker-guided cancer intervention of PDAC.

  3. Nicotine Addiction

    NARCIS (Netherlands)

    Andel I van; Rambali AB; Amsterdam JGC van; Wolterink G; Aerts LAGJM van; Vleeming W; TOX; SIR; BMT

    2003-01-01

    This report discusses the current knowledge on nicotine dependence, devoting a special chapter to smoking among youths, given that most smoking careers start in adolescence. The transition period, in which youths go from elementary to high school (ages 13-14), showes to be particularly risky for

  4. 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

  5. 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 ...

  6. 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.

  7. Animal models of nicotine exposure: relevance to second-hand smoking, electronic cigarette use and compulsive smoking

    Directory of Open Access Journals (Sweden)

    Ami eCohen

    2013-06-01

    Full Text Available Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake.

  8. 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

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

    2015-04-01

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

  12. Electronic Nicotine Delivery Systems.

    Science.gov (United States)

    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.

  13. Nicotinic plant poisoning.

    Science.gov (United States)

    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

  14. 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.

  15. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Naoya; Yamada, Shigeru [Division of Pharmacology, National Institute of Health Sciences (Japan); Asanagi, Miki [Division of Pharmacology, National Institute of Health Sciences (Japan); Faculty of Engineering, Department of Materials Science and Engineering, Yokohama National University (Japan); Sekino, Yuko [Division of Pharmacology, National Institute of Health Sciences (Japan); Kanda, Yasunari, E-mail: kanda@nihs.go.jp [Division of Pharmacology, National Institute of Health Sciences (Japan)

    2016-02-05

    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

  16. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

    International Nuclear Information System (INIS)

    Hirata, Naoya; Yamada, Shigeru; Asanagi, Miki; Sekino, Yuko; Kanda, Yasunari

    2016-01-01

    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

  17. Nicotine and tobacco

    Science.gov (United States)

    ... ease your withdrawal symptoms. Health experts warn that e-cigarettes are not a replacement therapy for cigarette smoking. ... not known exactly how much nicotine is in e-cigarette cartridges, because information on labels is often wrong.

  18. Nicotine Nasal Spray

    Science.gov (United States)

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

  19. Nicotine Oral Inhalation

    Science.gov (United States)

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

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

    Science.gov (United States)

    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.

  1. Insight into nicotine addiction

    Directory of Open Access Journals (Sweden)

    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.

  2. Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

    Science.gov (United States)

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

    2017-06-01

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

  3. 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.

  4. Thermochemical Properties of Nicotine Salts

    Directory of Open Access Journals (Sweden)

    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.

  5. 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...

  6. Why does anatabine, but not nicotine, accumulate in jasmonate-elicited cultured tobacco BY-2 cells?

    Science.gov (United States)

    Shoji, Tsubasa; Hashimoto, Takashi

    2008-08-01

    Suspension-cultured cells of Nicotiana tabacum cv. Bright Yellow-2 (BY-2) grow rapidly in a highly homogenous population and still exhibit the general behavior of plant cells, and thus are often used as model systems in several areas of plant molecular and cellular biology, including secondary metabolism. While the parental tobacco variety synthesizes nicotine as a major alkaloid, the cultured tobacco cells mainly produce a related alkaloid anatabine, instead of nicotine, when elicited with jasmonates. We report here that cultured BY-2 cells scarcely express N-methylputrescine oxidase (MPO) genes even after jasmonate elicitation. MPO is the second enzyme in the biosynthetic pathway that supplies the pyrrolidine moiety of nicotine and nornicotine, but is predicted to be dispensable for the biosynthesis of anatabine, anabasine and anatalline, which do not contain the pyrrolidine moiety. When MPO was overexpressed in tobacco BY-2 cells, nicotine synthesis was dramatically enhanced while anatabine formation was effectively suppressed. As a complementary approach, we suppressed MPO expression by RNA interference in tobacco hairy roots that normally accumulate nicotine. In the MPO-suppressed roots, the contents of anatabine, anabasine and anatalline, as well as N-methylputrescine and putrescine, markedly increased to compensate for suppressed formation of nicotine and nornicotine. These results identify the transcriptional regulation of MPO as a critical rate-limiting step that restricts nicotine formation in cultured tobacco BY-2 cells.

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

    Science.gov (United States)

    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.

  8. 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.

  9. Vitamin E Nicotinate

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. Anti-sense expression of putrescine N-methyltransferase confirms defensive role of nicotine in Nicotiana sylvestris against Manduca sexta

    NARCIS (Netherlands)

    Voelckel, C.; Krugel, T.; Gase, K.; Heidrich, N.; Van Dam, N.M.; Winz, R.; Baldwin, I.T.

    2001-01-01

    Several lines of evidence support the defensive function of nicotine production in the Nicotiana genus against a range of herbivores, but the evidence is largely correlative. To suppress nicotine production in planta and to test its defensive function, we expressed DNA of putrescine N-methyl

  12. Nicotine dependence and psychiatric disorders.

    Science.gov (United States)

    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

  13. The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats.

    Science.gov (United States)

    Palmatier, Matthew I; Kellicut, Marissa R; Brianna Sheppard, A; Brown, Russell W; Robinson, Donita L

    2014-11-01

    Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by

  14. 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.

  15. Self-administered nicotine differentially impacts body weight gain in obesity-prone and obesity-resistant rats.

    Science.gov (United States)

    Rupprecht, Laura E; Smith, Tracy T; Donny, Eric C; Sved, Alan F

    2017-07-01

    Obesity and tobacco smoking represent the largest challenges to public health, but the causal relationship between nicotine and obesity is poorly understood. Nicotine suppresses body weight gain, a factor impacting smoking initiation and the failure to quit, particularly among obese smokers. The impact of nicotine on body weight regulation in obesity-prone and obesity-resistant populations consuming densely caloric diets is unknown. In the current experiment, body weight gain of adult male rats maintained on a high energy diet (31.8% kcal from fat) distributed into obesity-prone (OP), obesity-resistant (OR) and an intermediate group, which was placed on standard rodent chow (Chow). These rats were surgically implanted with intravenous catheters and allowed to self-administer nicotine (0 or 60μg/kg/infusion, a standard self-administration dose) in 1-h sessions for 20 consecutive days. Self-administered nicotine significantly suppressed body weight gain but not food intake in OP and Chow rats. Self-administered nicotine had no effect on body weight gain in OR rats. These data suggest that: 1) OR rats are also resistant to nicotine-induced suppression of body weight gain; and 2) nicotine may reduce levels of obesity in a subset of smokers prone to obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. 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.

  17. Reduced nicotine product standards for combustible tobacco: building an empirical basis for effective regulation.

    Science.gov (United States)

    Donny, Eric C; Hatsukami, Dorothy K; Benowitz, Neal L; Sved, Alan F; Tidey, Jennifer W; Cassidy, Rachel N

    2014-11-01

    Both the Tobacco Control Act in the U.S. and Article 9 of the Framework Convention on Tobacco Control enable governments to directly address the addictiveness of combustible tobacco by reducing nicotine through product standards. Although nicotine may have some harmful effects, the detrimental health effects of smoked tobacco are primarily due to non-nicotine constituents. Hence, the health effects of nicotine reduction would likely be determined by changes in behavior that result in changes in smoke exposure. Herein, we review the current evidence on nicotine reduction and discuss some of the challenges in establishing the empirical basis for regulatory decisions. To date, research suggests that very low nicotine content cigarettes produce a desirable set of outcomes, including reduced exposure to nicotine, reduced smoking, and reduced dependence, without significant safety concerns. However, much is still unknown, including the effects of gradual versus abrupt changes in nicotine content, effects in vulnerable populations, and impact on youth. A coordinated effort must be made to provide the best possible scientific basis for regulatory decisions. The outcome of this effort may provide the foundation for a novel approach to tobacco control that dramatically reduces the devastating health consequences of smoked tobacco. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Characterizing the Genetic Basis for Nicotine Induced Cancer Development: A Transcriptome Sequencing Study.

    Directory of Open Access Journals (Sweden)

    Jasmin H Bavarva

    Full Text Available Nicotine is a known risk factor for cancer development and has been shown to alter gene expression in cells and tissue upon exposure. We used Illumina® Next Generation Sequencing (NGS technology to gain unbiased biological insight into the transcriptome of normal epithelial cells (MCF-10A to nicotine exposure. We generated expression data from 54,699 transcripts using triplicates of control and nicotine stressed cells. As a result, we identified 138 differentially expressed transcripts, including 39 uncharacterized genes. Additionally, 173 transcripts that are primarily associated with DNA replication, recombination, and repair showed evidence for alternative splicing. We discovered the greatest nicotine stress response by HPCAL4 (up-regulated by 4.71 fold and NPAS3 (down-regulated by -2.73 fold; both are genes that have not been previously implicated in nicotine exposure but are linked to cancer. We also discovered significant down-regulation (-2.3 fold and alternative splicing of NEAT1 (lncRNA that may have an important, yet undiscovered regulatory role. Gene ontology analysis revealed nicotine exposure influenced genes involved in cellular and metabolic processes. This study reveals previously unknown consequences of nicotine stress on the transcriptome of normal breast epithelial cells and provides insight into the underlying biological influence of nicotine on normal cells, marking the foundation for future studies.

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

    Science.gov (United States)

    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.

  20. Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns

    Science.gov (United States)

    Ajarem, Jamaan S.; Al-Basher, Gadh; Allam, Ahmed A.

    2017-01-01

    Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns. PMID:28588748

  1. Inhibition of nicotine-DNA adduct formation by polyphenolic compounds in vitro

    International Nuclear Information System (INIS)

    Cheng Yan; Wang Haifang; Sun Hongfang; Li Hongli

    2004-01-01

    Nicotine[3-(1-methyl-2-pyrrolidinyl)-pyridine], a major alkaloid in tobacco products, has proven to be a potential genotoxic compound. Some polyphenolic compounds can suppress the DNA adduction, and hence act as the potential inhibitors of carcinogenesis. In this study, the inhibitory effects of three polyphenolic compounds, curcumin (diferuloylmethane), resveratrol (trans-3, 5, 4-trihydroxystilbene) and tea polyphenols, on the nicotine-DNA adduction have been investigated in vitro using radiolabelled nicotine and liquid scintillation counting (LSC) technique. Also, the inhibition mechanism of these chemopreventive agents in regard to the activity of the biotransformation enzymes, including cytochrome P450 (CYP450), cytochrome b 5 (CYb 5 ) and glutathione S-transferase (GST), has been studied. The results demonstrated that these three polyphenols induced marked dose-dependent decrease in nicotine-DNA adducts as compared with the controls. The elimination rate of adducts reached above 46% at the highest dose for all the three agents with 51.6% for resveratrol. Correspondingly, three polyphenols all suppressed CYP450 and CYb 5 , whereas curcumin and resveratrol induced GST. The authors may arrive at a point that the three polyphenols are beneficial to prevent the nicotine adduct formation, and thus may be used to block the potential carcinogenesis induced by nicotine. (authors)

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

    Science.gov (United States)

    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.

  3. 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.

  4. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines

    International Nuclear Information System (INIS)

    Maneckjee, R.; Minna, J.D.

    1990-01-01

    Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for μ, δ, and κ opioid agonists and for nicotine and α-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas μ, δ, and κ opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides (β-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer

  5. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Maneckjee, R.; Minna, J.D. (National Cancer Institute-Navy Medical Oncology Branch, Bethesda, MD (USA) Uniformed Services Univ. of the Health Sciences, Bethesda, MD (USA))

    1990-05-01

    Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for {mu}, {delta}, and {kappa} opioid agonists and for nicotine and {alpha}-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas {mu}, {delta}, and {kappa} opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides ({beta}-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.

  6. Deconstructing continuous flash suppression.

    Science.gov (United States)

    Yang, Eunice; Blake, Randolph

    2012-03-08

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

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

    Science.gov (United States)

    Rosbrook, Kathryn; Green, Barry G

    2016-07-01

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

  8. 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.

  9. Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

    Science.gov (United States)

    Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

    2018-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Electronic Nicotine Delivery Systems Key Facts Infographic

    Data.gov (United States)

    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...

  11. Effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in male rhesus monkeys.

    Science.gov (United States)

    Schwienteck, Kathryn L; Negus, S Stevens; Poklis, Justin L; Banks, Matthew L

    2015-10-01

    One complicating factor in cocaine addiction may be concurrent exposure and potential dependence on nicotine. The aim of the present study was to determine the effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in rhesus monkeys (Macaca mulatta). For comparison, we also determined effects of the nicotinic receptor antagonist mecamylamine on cocaine versus food choice during continuous saline and nicotine treatment. Rhesus monkeys (N = 3) responded under a concurrent schedule of food pellet (1 g) and intravenous cocaine (0-0.1 mg/kg/injection) availability. Saline and ascending nicotine doses (0.1-1.0 mg/kg/hr, intravenous) were continuously infused for 7-day treatment periods and separated by 24-hr saline treatment periods. Acute effects of mecamylamine (0.32-1.8 mg/kg, intramuscular, 15 min pretreatment) were determined during continuous saline and 0.32-mg/kg/hr nicotine treatments. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice. Nicotine treatment did not alter cocaine versus food choice. In contrast, preference of 0.032 mg/kg/injection cocaine was attenuated 24 hr following termination of 0.32-mg/kg/hr nicotine treatment, despite no somatic abstinence signs being observed. Acute mecamylamine enhanced cocaine choice during saline treatment and mainly suppressed rates of behavior during nicotine treatment. Overall, continuous nicotine exposure, up to 1 mg/kg/hr, does not enhance cocaine choice and does not produce nicotine dependence, as demonstrated by the lack of abstinence signs. (c) 2015 APA, all rights reserved).

  12. Long-term nicotine exposure dampens LPS-induced nerve-mediated airway hyperreactivity in murine airways.

    Science.gov (United States)

    Xu, Yuan; Cardell, Lars-Olaf

    2017-09-01

    Nicotine is a major component of cigarette smoke. It causes addiction and is used clinically to aid smoke cessation. The aim of the present study is to investigate the effect of nicotine on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and to explore the potential involvement of neuronal mechanisms behind nicotine's effects in murine models in vivo and in vitro. BALB/c mice were exposed to nicotine in vivo via subcutaneous Alzet osmotic minipumps containing nicotine tartate salt solution (24 mg·kg -1 ·day -1 ) for 28 days. LPS (0.1 mg/ml, 20 µl) was administered intranasally for 3 consecutive days during the end of this period. Lung functions were measured with flexiVent. For the in vitro experiments, mice tracheae were organcultured with either nicotine (10 μM) or vehicle (DMSO, 0.1%) for 4 days. Contractile responses of the tracheal segments were measured in myographs following electric field stimulation (EFS; increasing frequencies of 0.2 to 12.8 Hz) before and after incubation with 10 µg/ml LPS for 1 h. Results showed that LPS induced AHR to methacholine in vivo and increased contractile responses to EFS in vitro. Interestingly, long-term nicotine exposure markedly dampened this LPS-induced AHR both in vitro and in vivo. Tetrodotoxin (TTX) inhibited LPS-induced AHR but did not further inhibit nicotine-suppressed AHR in vivo. In conclusion, long-term nicotine exposure dampened LPS-induced AHR. The effect of nicotine was mimicked by TTX, suggesting the involvement of neuronal mechanisms. This information might be used for evaluating the long-term effects of nicotine and further exploring of how tobacco products interact with bacterial airway infections. Copyright © 2017 the American Physiological Society.

  13. Electronic cigarettes and nicotine clinical pharmacology.

    Science.gov (United States)

    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.

  14. 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

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

    Science.gov (United States)

    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

  16. 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.

  17. Larval Helicoverpa zea Transcriptional, Growth and Behavioral Responses to Nicotine and Nicotiana tabacum

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    Linus Gog

    2014-09-01

    Full Text Available The polyphagous feeding habits of the corn earworm, Helicoverpa zea (Boddie, underscore its status as a major agricultural pest with a wide geographic distribution and host plant repertoire. To study the transcriptomic response to toxins in diet, we conducted a microarray analysis of H. zea caterpillars feeding on artificial diet, diet laced with nicotine and Nicotiana tabacum (L. plants. We supplemented our analysis with growth and aversion bioassays. The transcriptome reflects an abundant expression of proteases, chitin, cytochrome P450 and immune-related genes, many of which are shared between the two experimental treatments. However, the tobacco treatment tended to elicit stronger transcriptional responses than nicotine-laced diet. The salivary factor glucose oxidase, known to suppress nicotine induction in the plant, was upregulated by H. zea in response to tobacco but not to nicotine-laced diet. Reduced caterpillar growth rates accompanied the broad regulation of genes associated with growth, such as juvenile hormone epoxide hydrolase. The differential expression of chemosensory proteins, such as odorant binding-protein-2 precursor, as well as the neurotransmitter nicotinic-acetylcholine-receptor subunit 9, highlights candidate genes regulating aversive behavior towards nicotine. We suggest that an observed coincidental rise in cannibalistic behavior and regulation of proteases and protease inhibitors in H. zea larvae signify a compensatory response to induced plant defenses.

  18. Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Kirchgessner Annette

    2011-08-01

    Full Text Available Abstract Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell.

  19. [Assessment of anti-tremorogenic drugs--nicotine-induced tail-tremor model].

    Science.gov (United States)

    Suemaru, K; Kawasaki, H; Gomita, Y

    1997-06-01

    The repeated administration of nicotine at small doses, which do not produce whole body tremor or convulsion, causes tremor only in the tail (tail-tremor) of rats. The tremor is accompanied by locomotor hyperactivity without rigidity and immobility of the whole body, suggesting that the nicotine-induced tail-tremor model is useful for studying the mechanism underlying tremor associated with movement. The tail-tremor induced by nicotine was suppressed by mecamylamine, a nicotinic antagonist, but not by atropine or scopolamine, muscalinic antagonists. Moreover, the tail-tremor was suppressed by the beta-blockers propranolol and pindolol, as well as the benzodiazepines diazepam and clonazepam. Tremor at rest is observed only in Parkinson's disease, which is improved with anti-muscalinic drugs. Essential tremor is one of the typical tremors connected with movement (postural and kinetic tremor) and is improved with beta-blocker. These findings and results suggest that nicotine-induced tail-tremor is useful for the study of essential tremor in animal models.

  20. Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and β-adrenergic receptor signaling pathways

    International Nuclear Information System (INIS)

    Shin, Vivian Yvonne; Jin, H.C.; Ng, Enders K.O.; Yu Jun; Leung, W.K.; Cho, C.H.; Sung, J.J.Y.

    2008-01-01

    Induction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke that contributes to cancer development. However, the molecular mechanism(s) by which nicotine or NNK promotes gastric carcinogenesis remains largely unknown. We found that nicotine and NNK significantly enhanced cell proliferation in AGS cells that expressed both alpha7 nicotinic acetylcholine receptor (α7 nAChR) and β-adrenergic receptors. Treatment of cells with α-bungarotoxin (α-BTX, α7nAChR antagonist) or propranolol (β-adrenergic receptor antagonist) blocked NNK-induced COX-2/PGE 2 and cell proliferation, while nicotine-mediated cell growth and COX-2/PGE 2 induction can only be suppressed by propranolol, but not α-BTX. Moreover, in contrast to the dependence of growth promoting effect of nicotine on Erk activation, inhibitor of p38 mitogen-activated protein kinase (MAPK) repressed NNK-induced COX-2 upregulation and resulted in suppression of cell growth. In addition, nicotine and NNK mediated COX-2 induction via different receptors to modulate several G1/S transition regulatory proteins and promote gastric cancer cell growth. Selective COX-2 inhibitor (SC-236) caused G1 arrest and abrogated nicotine/NNK-induced cell proliferation. Aberrant expression of cyclin D1 and other G1 regulatory proteins are reversed by blockade of COX-2. These results pointed to the importance of adrenergic and nicotinic receptors in gastric tumor growth through MAPK/COX-2 activation, which may perhaps provide a chemoprevention strategy for cigarette smoke-related gastric carcinogenesis

  1. Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model.

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    Takeshi Yamamoto

    Full Text Available The prevalence of food allergy (FA has increased in developed countries over the past few decades. However, no effective drug therapies are currently available. Therefore, we investigated cholinergic anti-inflammatory pathway as a regulatory system to ameliorate disrupted mucosal immune homeostasis in the gut based on the pathophysiological elucidation of mucosal mast cells (MMCs in a murine FA model. BALB/c mice sensitized with ovalbumin received repeated oral ovalbumin for the development of FA. FA mice developed severe allergic diarrhea and exhibited enhanced type 2 helper T (Th2 cell immune responses in both systemic immunity and mucosal immunity, along with MMCs hyperplasia in the colon. MMCs were localized primarily in the strategic position of the mucosal epithelium. Furthermore, the allergic symptoms did not develop in p85α disrupted phosphoinositide-3 kinase-deficient mice that lacked mast cells in the gut. Vagal stimulation by 2-deoxy-D-glucose and drug treatment with nicotinic ACh receptor (nAChR agonists (nicotine and α7 nAChR agonist GTS-21 alleviated the allergic symptoms in the FA mice. Nicotine treatment suppressed MMCs hyperplasia, enhanced MPO and upregulated mRNA expression of Th1 and Th2 cytokines in the FA mice colon. MMCs, which are negatively regulated by α7 nAChRs, were often located in close proximity to cholinergic CGRP-immunoreactive nerve fibers in the FA mice colon. The present results reveal that the cholinergic neuroimmune interaction via α7 nAChRs on MMCs is largely involved in maintaining intestinal immune homeostasis and can be a target for a new therapy against mucosal immune diseases with homeostatic disturbances such as FA.

  2. Nicotine Contents in Some Commonly Used Toothpastes and Toothpowders: A Present Scenario

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    S. S. Agrawal

    2012-01-01

    Full Text Available The use of tobacco products as dentifrices is still prevalent in various parts of India. Tobacco use in dentifrices is a terrible scourge which motivates continued use despite its harmful effects. Indian legislation prohibits the use of nicotine in dentifrices. Nicotine is primarily injurious to people because it is responsible for tobacco addiction and is dependence forming. The present study was motivated by an interest in examining the presence of nicotine in these dentifrices. Our earlier report indicates the presence of nicotine in toothpowders. To further curb the menace of tobacco, our team again analysed the toothpowder brands of previous years and in toothpastes as well. Eight brands of commonly used toothpastes and toothpowders were evaluated by gas chromatography-mass spectroscopy. On the whole, there are a few successes but much remains to be done. Our findings indicated the presence of nicotine in two brands of dant manjans and four brands of toothpastes. Further our finding underscores the need for stringent regulations by the regulatory authorities for preventing the addition of nicotine in these dentifrices. Hence government policy needs to be targeted towards an effective control of tobacco in these dentifrices and should be properly addressed.

  3. Smoking, nicotine and the kidney

    NARCIS (Netherlands)

    Agarwal, Pramod Kumar

    2012-01-01

    Terwijl roken schadelijk is voor de nieren, lijkt nicotine juist een beschermend effect op deze organen te hebben. Matige alcoholconsumptie lijkt positieve effecten te hebben na niertransplantatie: het vermindert het risico op overlijden en het ontstaan van diabetes. Dat blijkt uit onderzoek van

  4. Primarily Experimental Results for a W Wire Array Z Pinch

    International Nuclear Information System (INIS)

    Kuai Bin; Aici, Qiu; Wang Liangping; Zeng Zhengzhong; Wang Wensheng; Cong Peitian; Gai Tongyang; Wei Fuli; Guo Ning; Zhang Zhong

    2006-01-01

    Primarily experimental results are given for a W wire array Z pinch imploded with up to 2 MA in 100 ns on a Qiangguang-I pulsed power generator. The configuration and parameters of the generator, the W wire array load assembly and the diagnostic system for the experiment are described. The total X-ray energy has been obtained with a averaged power of X-ray radiation of 1.28 TW

  5. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    International Nuclear Information System (INIS)

    Xu, Yuan; Cardell, Lars-Olaf

    2014-01-01

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B 2 receptor agonist) and des-Arg 9 -bradykinin- (selective B 1 receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE 2 . The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg 9 -bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B 2 receptors, but not those on B 1 . Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in some patients with asthma

  6. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  7. 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.

  8. Sex differences in the effect of wheel running on subsequent nicotine-seeking in a rat adolescent-onset self-administration model

    Science.gov (United States)

    Sanchez, Victoria; Moore, Catherine F; Brunzell, Darlene H; Lynch, Wendy J

    2014-01-01

    Rationale Wheel running attenuates nicotine-seeking in male adolescent rats; however it is not known if this effect extends to females. Objective To determine if wheel running during abstinence would differentially attenuate subsequent nicotine-seeking in male and female rats that had extended access to nicotine self-administration during adolescence. Methods Male (N = 49) and female (N = 43) adolescent rats self-administered saline or nicotine (5μg/kg) under an extended access (23-hour) paradigm. Following the last self-administration session, rats were moved to polycarbonate cages for an abstinence period where they either had access to a locked or unlocked running wheel for 2-hours/day. Subsequently, nicotine-seeking was examined under a within-session extinction/cue-induced reinstatement paradigm. Due to low levels of nicotine-seeking in females in both wheel groups, additional groups were included that were housed without access to a running wheel during abstinence. Results Females self-administered more nicotine as compared to males; however, within males and females, intake did not differ between groups prior to wheel assignment. Compared to saline controls, males and females that self-administered nicotine showed a significant increase in drug-seeking during extinction. Wheel running during abstinence attenuated nicotine-seeking during extinction in males. In females, access to either locked or unlocked wheels attenuated nicotine-seeking during extinction. While responding was reinstated by cues in both males and females, levels were modest and not significantly affected by exercise in this adolescent-onset model. Conclusions While wheel running reduced subsequent nicotine-seeking in males, access to a wheel, either locked or unlocked, was sufficient to suppress nicotine-seeking in females. PMID:24271035

  9. Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons.

    Science.gov (United States)

    Corsini, Silvia; Tortora, Maria; Nistri, Andrea

    2016-11-15

    Impaired uptake of glutamate builds up the extracellular level of this excitatory transmitter to trigger rhythmic neuronal bursting and delayed cell death in the brainstem motor nucleus hypoglossus. This process is the expression of the excitotoxicity that underlies motoneuron degeneration in diseases such as amyotrophic lateral sclerosis affecting bulbar motoneurons. In a model of motoneuron excitotoxicity produced by pharmacological block of glutamate uptake in vitro, rhythmic bursting is suppressed by activation of neuronal nicotinic receptors with their conventional agonist nicotine. Emergence of bursting is facilitated by nicotinic receptor antagonists. Following excitotoxicity, nicotinic receptor activity decreases mitochondrial energy dysfunction, endoplasmic reticulum stress and production of toxic radicals. Globally, these phenomena synergize to provide motoneuron protection. Nicotinic receptors may represent a novel target to contrast pathological overactivity of brainstem motoneurons and therefore to prevent their metabolic distress and death. Excitotoxicity is thought to be one of the early processes in the onset of amyotrophic lateral sclerosis (ALS) because high levels of glutamate have been detected in the cerebrospinal fluid of such patients due to dysfunctional uptake of this transmitter that gradually damages brainstem and spinal motoneurons. To explore potential mechanisms to arrest ALS onset, we used an established in vitro model of rat brainstem slice preparation in which excitotoxicity is induced by the glutamate uptake blocker dl-threo-β-benzyloxyaspartate (TBOA). Because certain brain neurons may be neuroprotected via activation of nicotinic acetylcholine receptors (nAChRs) by nicotine, we investigated if nicotine could arrest excitotoxic damage to highly ALS-vulnerable hypoglossal motoneurons (HMs). On 50% of patch-clamped HMs, TBOA induced intense network bursts that were inhibited by 1-10 μm nicotine, whereas nAChR antagonists

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

    OpenAIRE

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

    2016-01-01

    Nicotine dependence and smoking frequency are critical factors for smoking cessation. The aims of this study are (1) to determine if nicotine dependence Fagerstrom Test for Nicotine Dependence (FTND) scores are associated with urinary levels of nicotine metabolites, (2) to assess the relationship of hydroxycotinine/cotinine ratio with FTND score and cigarettes smoked per day (CPD), and (3) to identify significant predictors of cigarettes per day among biomarker concentrations and individual F...

  11. Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

    Science.gov (United States)

    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.

  12. Human punishment is not primarily motivated by inequality.

    Science.gov (United States)

    Marczyk, Jesse

    2017-01-01

    Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player's payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value.

  13. Human punishment is not primarily motivated by inequality

    Science.gov (United States)

    Marczyk, Jesse

    2017-01-01

    Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player’s payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value. PMID:28187166

  14. Human punishment is not primarily motivated by inequality.

    Directory of Open Access Journals (Sweden)

    Jesse Marczyk

    Full Text Available Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player's payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value.

  15. Stimulation of Alpha7 Nicotinic Acetylcholine Receptor Attenuates Nicotine-Induced Upregulation of MMP, MCP-1, and RANTES through Modulating ERK1/2/AP-1 Signaling Pathway in RAW264.7 and MOVAS Cells

    Directory of Open Access Journals (Sweden)

    Liping Liu

    2017-01-01

    Full Text Available Vagus nerve stimulation through alpha7 nicotine acetylcholine receptors (α7-nAChR signaling had been demonstrated attenuation of inflammation. This study aimed to determine whether PNU-282987, a selective α7-nAChR agonist, affected activities of matrix metalloproteinase (MMP and inflammatory cytokines in nicotine-treatment RAW264.7 and MOVAS cells and to assess the underlying molecular mechanisms. RAW264.7 and MOVAS cells were treated with nicotine at different concentrations (0, 1, 10, and 100 ng/ml for 0–120 min. Nicotine markedly stimulated the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2 and c-Jun in RAW264.7 cells. Pretreatment with U0126 significantly suppressed phosphorylation of ERK1/2 and further attenuated nicotine-induced activation of c-Jun and upregulation of MMP-2, MMP-9, monocyte chemotactic protein- (MCP- 1, and regulated upon activation normal T cell expressed and secreted (RANTES. Similarly, nicotine treatment also increased phosphorylation of c-Jun and expressions of MMP-2, MMP-9, MCP-1, and RANTES in MOVAS cells. When cells were pretreated with PNU-282987, nicotine-induced activations of ERK1/2 and c-Jun in RAW264.7 cells and c-Jun in MOVAS cells were effectively inhibited. Furthermore, nicotine-induced secretions of MMP-2, MMP-9, MCP-1, and RANTES were remarkably downregulated. Treatment with α7-nAChR agonist inhibits nicotine-induced upregulation of MMP and inflammatory cytokines through modulating ERK1/2/AP-1 signaling in RAW264.7 cells and AP-1 in MOVAS cells, providing a new therapeutic for abdominal aortic aneurysm.

  16. Suppressed Belief

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    Komarine Romdenh-Romluc

    2009-12-01

    Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

  17. Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.

    Science.gov (United States)

    Tie, Kai; Zhang, Xianrong; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Wang, Hui; Chen, Liaobin

    2016-02-01

    This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/kg/d from gestational d 11 to 20. The female adult offspring with or without PNE were forced with a strenuous treadmill running for 6 wk to induce OA. Nicotine's effects on fetal articular chondrocytes were studied by exposing chondrocytes to nicotine for 10 d, and dihydro-β-erythroidine, a selective α4β2-nicotinic acetylcholine receptor (nAChR) inhibitor, was used to identify the change of nicotine's effect. For adult offspring, increased cartilage destruction and accelerated OA progression were observed in the PNE group with running; the expression of α1 chain of type II collagen (Col2A1), aggrecan, SRY-type high mobility group box 9 (Sox9), and IGF1 signaling molecules in the cartilage of PNE offspring were decreased. For fetuses, elevated serum corticosteroid and nicotine levels and suppressed IGF1 levels were observed; expression of Col2A1, aggrecan, Sox9, and IGF1 were reduced. The result of chondrocytes revealed that nicotine impeded the expression of Col2A1, aggrecan, and IGF1; blocking α4β2-nAChR rescued nicotine's suppression. In conclusion, PNE increases the susceptibility of adult offspring to OA; the potential mechanism involves IGF1 low-functional programming in articular cartilage caused directly by the action of nicotine on α4β2-nAChR. © FASEB.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  3. 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...

  4. Measurement of nicotine in household dust

    International Nuclear Information System (INIS)

    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

  5. Influence of Methionine Supplementation on Nicotine Teratogenicity ...

    African Journals Online (AJOL)

    Human and animal studies have shown that maternal tobacco smoking during pregnancy adversely affects pre and postnatal growth and increases the risk of fetal mortality. The aim of the present study was to determine the toxicity of nicotine and protective effect of methionine on the toxic effects of nicotine. Pregnant ...

  6. VOLTAMMETRIC DETERMINATION OF NICOTINE IN CIGARETTE ...

    African Journals Online (AJOL)

    Preferred Customer

    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.

  7. 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.

  8. 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.

  9. 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.

  10. 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 ...

  11. 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

  12. Immunomodulatory Role of Ocimum gratissimum and Ascorbic Acid against Nicotine-Induced Murine Peritoneal Macrophages In Vitro

    Directory of Open Access Journals (Sweden)

    Santanu Kar Mahapatra

    2011-01-01

    Full Text Available The aim of this present study was to evaluate the immune functions and immune responses in nicotine-induced (10 mM macrophages and concurrently establish the immunomodulatory role of aqueous extract of Ocimum gratissimum (Ae-Og and ascorbic acid. In this study, nitrite generations and some phenotype functions by macrophages were studied. Beside that, release of Th1 cytokines (TNF-α, IL-12 and Th2 cytokines (IL-10, TGF-β was measured by ELISA, and the expression of these cytokines at mRNA level was analyzed by real-time PCR. Ae-Og, at a dose of 10 μg/mL, significantly reduced the nicotine-induced NO generation and iNOSII expression. Similar kinds of response were observed with supplementation of ascorbic acid (0.01 mM. The administration of Ae-Og and ascorbic acid increased the decreased adherence, chemotaxis, phagocytosis, and intracellular killing of bacteria in nicotine-treated macrophages. Ae-Og and ascorbic acid were found to protect the murine peritoneal macrophages through downregulation of Th1 cytokines in nicotine-treated macrophages with concurrent activation of Th2 responses. These findings strongly enhanced our understanding of the molecular mechanism leading to nicotine-induced suppression of immune functions and provide additional rationale for application of anti-inflammatory therapeutic approaches by O. gratissimum and ascorbic acid for different inflammatory disease prevention and treatment during nicotine toxicity.

  13. 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

  14. 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...

  15. 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).

  16. Distinguishing among potential mechanisms of singleton suppression.

    Science.gov (United States)

    Gaspelin, Nicholas; Luck, Steven J

    2018-04-01

    Previous research has revealed that people can suppress salient stimuli that might otherwise capture visual attention. The present study tests between 3 possible mechanisms of visual suppression. According to first-order feature suppression models , items are suppressed on the basis of simple feature values. According to second-order feature suppression models , items are suppressed on the basis of local discontinuities within a given feature dimension. According to global-salience suppression models , items are suppressed on the basis of their dimension-independent salience levels. The current study distinguished among these models by varying the predictability of the singleton color value. If items are suppressed by virtue of salience alone, then it should not matter whether the singleton color is predictable. However, evidence from probe processing and eye movements indicated that suppression is possible only when the color values are predictable. Moreover, the ability to suppress salient items developed gradually as participants gained experience with the feature that defined the salient distractor. These results are consistent with first-order feature suppression models, and are inconsistent with the other models of suppression. In other words, people primarily suppress salient distractors on the basis of their simple features and not on the basis of salience per se. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

    Science.gov (United States)

    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.

  18. Interocular suppression

    Science.gov (United States)

    Tuna, Ana Rita; Almeida Neves Carrega, Filipa; Nunes, Amélia Fernandes

    2017-08-01

    The objective of this work is to quantify the suppressive imbalance, based on the manipulation of ocular luminance, between a group of subjects with normal binocular vision and a group of subjects with amblyopia. The result reveals that there are statistically significant differences in interocular dominance between two groups, evidencing a greater suppressive imbalance in amblyopic subjects. The technique used, proved to be a simple, easy to apply and economic method, for quantified ocular dominance. It is presented as a technique with the potential to accompany subjects with a marked dominance in one of the eyes that makes fusion difficult.

  19. Similar precipitated withdrawal effects on intracranial self-stimulation during chronic infusion of an e-cigarette liquid or nicotine alone.

    Science.gov (United States)

    Harris, A C; Muelken, P; Smethells, J R; Krueger, M; LeSage, M G

    2017-10-01

    The FDA recently extended their regulatory authority to electronic cigarettes (ECs). Because the abuse liability of ECs is a leading concern of the FDA, animal models are urgently needed to identify factors that influence the relative abuse liability of these products. The ability of tobacco products to induce nicotine dependence, defined by the emergence of anhedonia and other symptoms of nicotine withdrawal following cessation of their use, contributes to tobacco abuse liability. The present study compared the severity of precipitated withdrawal during chronic infusion of nicotine alone or nicotine-dose equivalent concentrations of three different EC refill liquids in rats, as indicated by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Because these EC liquids contain constituents that may enhance their abuse liability (e.g., minor alkaloids), we hypothesized that they would be associated with greater withdrawal effects than nicotine alone. Results indicated that the nicotinic acetylcholine receptor antagonist mecamylamine precipitated elevations in ICSS thresholds in rats receiving a chronic infusion of nicotine alone or EC liquids (3.2mg/kg/day, via osmotic pump). Magnitude of this effect did not differ between formulations. Our findings indicate that nicotine alone is the primary CNS determinant of the ability of ECs to engender dependence. Combined with our previous findings that nicotine alone and these EC liquids do not differ in other preclinical addiction models, these data suggest that product standards set by the FDA to reduce EC abuse liability should primarily target nicotine, other constituents with peripheral sensory effects (e.g. flavorants), and factors that influence product appeal (e.g., marketing). Copyright © 2017 Elsevier Inc. All rights reserved.

  20. 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.

  1. 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...

  2. Slower nicotine metabolism among postmenopausal Polish smokers.

    Science.gov (United States)

    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.

  3. Electronic cigarettes and nicotine clinical pharmacology

    OpenAIRE

    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 abst...

  4. 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.

  5. 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.

  6. Layer-specific interference with cholinergic signaling in the prefrontal cortex by smoking concentrations of nicotine

    NARCIS (Netherlands)

    Poorthuis, R.B.; Bloem, B.R.; Verhoog, M.B.; Mansvelder, H.D.

    2013-01-01

    Adolescence is a period in which the developing prefrontal cortex (PFC) is sensitive to maladaptive changes when exposed to nicotine. Nicotine affects PFC function and repeated exposure to nicotine during adolescence impairs attention performance and impulse control during adulthood. Nicotine

  7. 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...

  8. 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

  9. 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

  10. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  12. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. Tobacco and Nicotine Product Testing

    Science.gov (United States)

    Biener, Lois; Leischow, Scott J.; Zeller, Mitch R.

    2012-01-01

    Introduction: Tobacco product testing is a critical component of the Family Smoking Prevention and Tobacco Control Act (FSPTCA), which grants the Food and Drug Administration the authority to regulate tobacco products. The availability of methods and measures that can provide accurate data on the relative health risks across types of tobacco products, brands, and subbrands of tobacco products on the validity of any health claims associated with a product, and on how consumers perceive information on products toxicity or risks is crucial for making decisions on the product's potential impact on public health. These tools are also necessary for making assessments of the impact of new indications for medicinal products (other than cessation) but more importantly of tobacco products that may in the future be marketed as cessation tools. Objective: To identify research opportunities to develop empirically based and comprehensive methods and measures for testing tobacco and other nicotine-containing products so that the best science is available when decisions are made about products or policies. Methods: Literature was reviewed to address sections of the FSPTCA relevant to tobacco product evaluation; research questions were generated and then reviewed by a committee of research experts. Results: A research agenda was developed for tobacco product evaluation in the general areas of toxicity and health risks, abuse liability, consumer perception, and population effects. Conclusion: A cohesive, systematic, and comprehensive assessment of tobacco products is important and will require building consensus and addressing some crucial research questions. PMID:21460383

  16. Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence.

    Science.gov (United States)

    Kendler, Kenneth S; Myers, John; Prescott, Carol A

    2007-11-01

    Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. Lifetime history by structured clinical interview. General community. Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence

  17. Classical genetic analyses of responses to nicotine and ethanol in crosses derived from long- and short-sleep mice.

    Science.gov (United States)

    de Fiebre, C M; Collins, A C

    1992-04-01

    A classical (Mendelian) genetic analysis of responses to ethanol and nicotine was conducted in crosses derived from mouse lines which were selectively bred for differential duration of loss of the righting response (sleep-time) after ethanol. Dose-response curves for these mice, the long- and short-sleep mouse lines, as well as the derived F1, F2 and backcross (F1 x long-sleep and F1 x short-sleep) generations were generated for several measures of nicotine and ethanol sensitivity. Ethanol sensitivity was assessed using the sleep-time measure. Nicotine sensitivity was tested using a battery of behavioral and physiological tests which included measures of seizure activity, respiration rate, acoustic startle response, Y-maze activities (both crossing and rearing activities), heart rate and body temperature. The inheritance of sensitivities to both of these agents appears to be polygenic and inheritance can be explained primarily by additive genetic effects with some epistasis. Sensitivity to the ethanol sleep-time measure was genetically correlated with sensitivity to both nicotine-induced hypothermia and seizures; the correlation was greater between sleep-time and hypothermia. These data indicate that there is overlap in the genetic regulation of sensitivity to both ethanol and nicotine as measured by some, but not all, tests.

  18. Nicotinic modulaton of neuronal networks: from receptors to cognition

    NARCIS (Netherlands)

    Mansvelder, H.D.; van Aerde, K.I.; Couey, J.J.; Brussaard, A.B.

    2006-01-01

    Rationale: Nicotine affects many aspects of human cognition, including attention and memory. Activation of nicotinic acetylcholine receptors (nAChRs) in neuronal networks modulates activity and information processing during cognitive tasks, which can be observed in electroencephalograms (EEGs) and

  19. Design, formulation and evaluation of nicotine chewing gum

    Directory of Open Access Journals (Sweden)

    Abolfazl Aslani

    2012-01-01

    Conclusion: 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.

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

    Science.gov (United States)

    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

  1. 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.

  2. A clinical laboratory model for evaluating the acute effects of electronic "cigarettes": nicotine delivery profile and cardiovascular and subjective effects.

    Science.gov (United States)

    Vansickel, Andrea R; Cobb, Caroline O; Weaver, Michael F; Eissenberg, Thomas E

    2010-08-01

    Electronic "cigarettes" are marketed to tobacco users as potential reduced exposure products (PREP), albeit with little information regarding electronic cigarette user toxicant exposure and effects. This information may be obtained by adapting clinical laboratory methods used to evaluate other PREPs for smokers. Thirty-two smokers participated in four independent Latin-square ordered conditions that differed by product: own brand cigarette, "NPRO" electronic cigarettes (NPRO EC; 18 mg cartridge), "Hydro" electronic cigarettes (Hydro EC; 16 mg cartridge), or sham (unlit cigarette). Participants took 10 puffs at two separate times during each session. Plasma nicotine and carbon monoxide (CO) concentration, heart rate, and subjective effects were assessed. Own brand significantly increased plasma nicotine and CO concentration and heart rate within the first five minutes of administration whereas NPRO EC, Hydro EC, and sham smoking did not. Own brand, NPRO EC, and Hydro EC (but not sham) significantly decreased tobacco abstinence symptom ratings and increased product acceptability ratings. The magnitude of symptom suppression and increased acceptability was greater for own brand than for NPRO EC and Hydro EC. Under these acute testing conditions, neither of the electronic cigarettes exposed users to measurable levels of nicotine or CO, although both suppressed nicotine/tobacco abstinence symptom ratings. This study illustrates how clinical laboratory methods can be used to understand the acute effects of these and other PREPs for tobacco users. The results and methods reported here will likely be relevant to the evaluation and empirically based regulation of electronic cigarettes and similar products. (c)2010 AACR.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  5. 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.

  6. 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

  7. 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...

  8. The metabolic fate of nectar nicotine in worker honey bees.

    Science.gov (United States)

    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.

  9. Solubility of nicotinic acid in water, ethanol, acetone, diethyl ether, acetonitrile, and dimethyl sulfoxide

    International Nuclear Information System (INIS)

    Gonçalves, Elsa M.; Minas da Piedade, Manuel E.

    2012-01-01

    Highlights: ► We determined the solubility of nicotinic acid in six solvents by the gravimetric method. ► We found that, regardless of the solvent, the same monoclinic solid phase was in equilibrium with the solution. ► We determined the activity coefficients of nicotinic acid in the six solvents. ► We found that the solubility trends seem to be determined by the polarity and polarizability of the solvent. - Abstract: The mole fraction equilibrium solubility of nicotinic acid in six solvents (water, ethanol, dimethyl sulfoxide, acetone, acetonitrile and diethyl ether) differing in polarity, polarizability, and hydrogen-bonding ability, was determined over the temperature range (283 to 333) K, using the gravimetric method. The results obtained led to the solubility order dimethyl sulfoxide (DMSO) ≫ ethanol > water > acetone > diethyl ether > acetonitrile. An analysis based on various solvent descriptors, indicated that this trend seems to be mainly determined by the polarity and polarizability of the solvent. The activity coefficients of nicotinic acid in the different solvents, under saturation conditions, were determined as a function of the temperature and it was found that DMSO exhibits enhanced solubility relative to an ideal solution while the opposite is observed for all other solvents. Both the solvent and the fact that nicotinic acid is primarily zwitterionic in aqueous solution and non-zwitterionic in non-aqueous media, did not affect the nature of the solid phases in equilibrium with the different solutions. Indeed, X-ray powder diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry analysis indicated that, despite some differences in particle size and morphology, the starting material and the solid products obtained at the end of the solubility studies in the six solvents used in this work were all crystalline and corresponded to the same monoclinic phase.

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

    Science.gov (United States)

    ... 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: ...

  11. Hormones, Nicotine and Cocaine: Clinical Studies

    Science.gov (United States)

    Mello, Nancy K.

    2009-01-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

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

    Directory of Open Access Journals (Sweden)

    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

  13. Nicotine facilitates memory consolidation in perceptual learning.

    Science.gov (United States)

    Beer, Anton L; Vartak, Devavrat; Greenlee, Mark W

    2013-01-01

    Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices. The cholinergic system is known to modulate declarative learning. In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation. However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning. Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT). One group received chewing tobacco containing nicotine for 1 h directly following the TDT training. The other group received a similar tasting control substance without nicotine. Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group. When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training. These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex. A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group. These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors. Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning). In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning. Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. The α7 nicotinic acetylcholine receptor complex

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Mikkelsen, Jens D

    2012-01-01

    The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds and prote......The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds...

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

    Science.gov (United States)

    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...

  16. 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

  17. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-09-01

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

  20. 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.)

  1. 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.

  2. 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

  3. Docking to flexible nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Sander, Tommy; Bruun, Anne T; Balle, Thomas

    2010-01-01

    Computational docking to nicotinic acetylcholine receptors (nAChRs) and other members of the Cys-loop receptor family is complicated by the flexibility of the so-called C-loop. As observed in the large number of published crystal structures of the acetylcholine binding protein (AChBP), a structural...

  4. Structural Studies of Nicotinic Acetylcholine Receptors

    DEFF Research Database (Denmark)

    Shahsavar, Azadeh; Gajhede, Michael; Kastrup, Jette

    2016-01-01

    Nicotinic acetylcholine receptors (nAChRs) are members of the pentameric ligand-gated ion channel superfamily that play important roles in control of neurotransmitter release in the central and peripheral nervous system. These receptors are important therapeutic targets for development of drugs...

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Preliminary results of an examination of electronic cigarette user puff topography: the effect of a mouthpiece-based topography measurement device on plasma nicotine and subjective effects.

    Science.gov (United States)

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

    2015-02-01

    Electronic cigarettes (ECIGs) heat a nicotine-containing solution; the resulting aerosol is inhaled by the user. Nicotine delivery may be affected by users' puffing behavior (puff topography), and little is known about the puff topography of ECIG users. Puff topography can be measured using mouthpiece-based computerized systems. However, the extent to which a mouthpiece influences nicotine delivery and subjective effects in ECIG users is unknown. Plasma nicotine concentration, heart rate, and subjective effects were measured in 13 experienced ECIG users who used their preferred ECIG and liquid (≥ 12 mg/ml nicotine) during 2 sessions (with or without a mouthpiece). In both sessions, participants completed an ECIG use session in which they were instructed to take 10 puffs with 30-second inter-puff intervals. Puff topography was recorded in the mouthpiece condition. Almost all measures of the effects of ECIG use were independent of topography measurement. Collapsed across session, mean plasma nicotine concentration increased by 16.8 ng/ml, and mean heart rate increased by 8.5 bpm (ps topography measurement equipment, ECIG-using participants took larger and longer puffs with lower flow rates. In experienced ECIG users, measuring ECIG topography did not influence ECIG-associated nicotine delivery or most measures of withdrawal suppression. Topography measurement systems will need to account for the low flow rates observed for ECIG users. © 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  13. The role of alpha-7 nicotinic receptors in food intake behaviors

    Directory of Open Access Journals (Sweden)

    Kristina L. McFadden

    2014-06-01

    Full Text Available Nicotine alters appetite and energy expenditure, leading to changes in body weight. While the exact mechanisms underlying these effects are not fully established, both central and peripheral involvement of the alpha-7 nicotinic acetylcholine receptor (α7nAChR has been suggested. Centrally, the α7nAChR modulates activity of hypothalamic neurons involved in food intake regulation, including proopiomelanocortin (POMC and neuropeptide Y (NPY. α7nAChRs also modulate glutamatergic and dopaminergic systems controlling reward processes that affect food intake. Additionally, α7nAChRs are important peripheral mediators of chronic inflammation, a key contributor to health problems in obesity. This review focuses on nicotinic cholinergic effects on eating behaviors, specifically those involving the α7nAChR, with the hypothesis that α7nAChR agonism leads to appetite suppression. Recent studies are highlighted that identify links between α7nAChR expression and obesity, insulin resistance, and diabetes and describe early findings showing an α7nAChR agonist to be associated with reduced weight gain in a mouse model of diabetes. Given these effects, the α7nAChR may be a useful therapeutic target for strategies to treat and manage obesity.

  14. 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

  15. 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.

  16. 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.

  17. Electronic cigarettes are a source of thirdhand exposure to nicotine.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Adsorption of nicotine on different zeolite types, from aqueous solutions

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. 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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. 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

  10. 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.

  11. 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)

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

    Science.gov (United States)

    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.

  13. Eliciting nicotine craving with virtual smoking cues.

    Science.gov (United States)

    Gamito, Pedro; Oliveira, Jorge; Baptista, André; Morais, Diogo; Lopes, Paulo; Rosa, Pedro; Santos, Nuno; Brito, Rodrigo

    2014-08-01

    Craving is a strong desire to consume that emerges in every case of substance addiction. Previous studies have shown that eliciting craving with an exposure cues protocol can be a useful option for the treatment of nicotine dependence. Thus, the main goal of this study was to develop a virtual platform in order to induce craving in smokers. Fifty-five undergraduate students were randomly assigned to two different virtual environments: high arousal contextual cues and low arousal contextual cues scenarios (17 smokers with low nicotine dependency were excluded). An eye-tracker system was used to evaluate attention toward these cues. Eye fixation on smoking-related cues differed between smokers and nonsmokers, indicating that smokers focused more often on smoking-related cues than nonsmokers. Self-reports of craving are in agreement with these results and suggest a significant increase in craving after exposure to smoking cues. In sum, these data support the use of virtual environments for eliciting craving.

  14. Degradation of Nicotine in Chlorinated Water: Pathways and ...

    Science.gov (United States)

    Report The objective of the study is to illustrate how drinking water would affect alkaloid pesticides, and to address the issue by (a) investigating the fate of nicotine in chlorinated drinking water and deionized water, (b) determining the reaction rate and pathway of the reaction between nicotine and aqueous chlorine, (c) identifying nicotine’s degradation products, and (d) providing data that can be used to assess the potential threat from nicotine in drinking water.

  15. Adsorption of nicotine on different zeolite types, from aqueous solutions

    OpenAIRE

    Stošić Dušan K.; Dondur Vera T.; Rac Vladislav A.; Rakić Vesna M.; Zakrzewska Joanna S.

    2007-01-01

    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, nico...

  16. 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

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

    Science.gov (United States)

    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

  18. 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.

  19. 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.

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

    Science.gov (United States)

    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).

  1. 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.

  2. Reciprocal activation of α5-nAChR and STAT3 in nicotine-induced human lung cancer cell proliferation.

    Science.gov (United States)

    Zhang, Yao; Jia, Yanfei; Li, Ping; Li, Huanjie; Xiao, Dongjie; Wang, Yunshan; Ma, Xiaoli

    2017-07-20

    Cigarette smoking is the top environmental risk factor for lung cancer. Nicotine, the addictive component of cigarettes, induces lung cancer cell proliferation, invasion and migration via the activation of nicotinic acetylcholine receptors (nAChRs). Genome-wide association studies (GWAS) show that CHRNA5 gene encoding α5-nAChR is especially relevant to lung cancer. However, the mechanism of this subunit in lung cancer is not clear. In the present study, we demonstrate that the expression of α5-nAChR is correlated with phosphorylated STAT3 (pSTAT3) expression, smoking history and lower survival of non-small cell lung cancer (NSCLC) samples. Nicotine increased the levels of α5-nAChR mRNA and protein in NSCLC cell lines and activated the JAK2/STAT3 signaling cascade. Nicotine-induced activation of JAK2/STAT3 signaling was inhibited by the silencing of α5-nAChR. Characterization of the CHRNA5 promoter revealed four STAT3-response elements. ChIP assays confirmed that the CHRNA5 promoter contains STAT3 binding sites. By silencing STAT3 expression, nicotine-induced upregulation of α5-nAChR was suppressed. Downregulation of α5-nAChR and/or STAT3 expression inhibited nicotine-induced lung cancer cell proliferation. These results suggest that there is a feedback loop between α5-nAChR and STAT3 that contributes to the nicotine-induced tumor cell proliferation, which indicates that α5-nAChR is an important therapeutic target involved in tobacco-associated lung carcinogenesis. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  4. Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

    International Nuclear Information System (INIS)

    Wang, Tingting; Chen, Man; Liu, Lian; Cheng, Huaiyan; Yan, You-E; Feng, Ying-Hong; Wang, Hui

    2011-01-01

    Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: ► Nicotine-induced StAR inhibition in two human adrenal cell models. ► Nicotine-induced single CpG site methylation in StAR promoter. ► Persistent StAR inhibition and single CpG methylation after nicotine termination. ► Single CpG methylation located at Pax6 binding motif regulates St

  5. Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Chen, Man; Liu, Lian [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Cheng, Huaiyan [Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Yan, You-E [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Feng, Ying-Hong, E-mail: yhfeng@usuhs.edu [Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2011-12-15

    Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: Black-Right-Pointing-Pointer Nicotine-induced StAR inhibition in two human adrenal cell models. Black-Right-Pointing-Pointer Nicotine-induced single CpG site methylation in StAR promoter. Black-Right-Pointing-Pointer Persistent StAR inhibition and single CpG methylation after nicotine termination

  6. Effects of Inoculum Amount, Initial pH, and Nicotine Load on the Set-Up of Bioaugmented System with Pseudomonas Sp. HF-1 to Treat Tobacco Wastewater

    Directory of Open Access Journals (Sweden)

    Kun Zhang

    2014-01-01

    Full Text Available This study evaluated and optimized the influence of inoculum amount, initial pH, and nicotine load on the construction of Pseudomonas sp. HF-1 bioaugmented system for tobacco wastewater treatment. The results demonstrated that the optimum condition for the set-up of strain HF-1 bioaugmented system was 1.10 mg/g (dry weight of strain HF-1/dry weight of activated sludge of inoculum amount, initial pH 7.0, and 250–1000 mg/L nicotine load. Higher than 1.10 mg/g could lead to noncolonization of strain HF-1 in activated sludge and failure of set-up of this bioaugmented system. Higher than pH 8.0 could restrain the colonization of strain HF-1 in activated sludge. Even though strain HF-1 colonizes in the activated sludge when pH was above 8.0, the removal of nicotine and total organic carbon (TOC was suppressed due to low activities of bacteria in the activated sludge. Nicotine load did not show inhibition effect on set-up of bioaugmented system, but the ability of TOC removal was restrained when the nicotine load was above 1000 mg/L. This work could offer vital parameters for the set-up of bioaugmented system to treat tobacco wastewater in engineering.

  7. 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

  8. Environmental fate and effects of nicotine released during cigarette production.

    Science.gov (United States)

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

    2008-07-01

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

  9. Prefrontal gamma-aminobutyric acid type A receptor insertion controls cue-induced relapse to nicotine seeking.

    Science.gov (United States)

    Lubbers, Bart R; van Mourik, Yvar; Schetters, Dustin; Smit, August B; De Vries, Taco J; Spijker, Sabine

    2014-11-01

    Current smoking cessation therapies offer limited success, as relapse rates remain high. Nicotine, which is the major component of tobacco smoke, is thought to be primarily responsible for the addictive properties of tobacco. However, little is known about the molecular mechanisms underlying nicotine relapse, hampering development of more effective therapies. The objective of this study was to elucidate the role of medial prefrontal cortex (mPFC) glutamatergic and gamma-aminobutyric acid (GABA)ergic receptors in controlling relapse to nicotine seeking. Using an intravenous self-administration model, we studied glutamate and gamma-aminobutyric acid receptor regulation in the synaptic membrane fraction of the rat mPFC following extinction and cue-induced relapse to nicotine seeking. Subsequently, we locally intervened at the level of GABAergic signaling by using a mimetic peptide of the GABA receptor associated protein-interacting domain of GABA type A (GABAA) receptor subunit γ2 (TAT-GABAγ2) and muscimol, a GABAA receptor agonist. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors were not regulated after the 30-min relapse test. However, GABAA receptor subunits α1 and γ2 were upregulated, and interference with GABAA receptor insertion in the cell membrane using the TAT-GABAγ2 peptide in the dorsal mPFC, but not the ventral mPFC, significantly increased responding during relapse. Increasing GABAA transmission with muscimol in the dorsal and ventral mPFC attenuated relapse. These data indicate that cue-induced relapse entails a GABAergic plasticity mechanism that limits nicotine seeking by restoring inhibitory control in the dorsal mPFC. GABAA receptor-mediated neurotransmission in the dorsal mPFC constitutes a possible future therapeutic target for maintaining smoking abstinence. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2017-04-01

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

  15. 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

  16. 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...

  17. Melatonin protects uterus and oviduct exposed to nicotine in mice

    Directory of Open Access Journals (Sweden)

    Seyed Saadat Seyedeh Nazanin

    2014-03-01

    Full Text Available Smoking is associated with higher infertility risk. The aim of this study was to evaluate protective effects of melatonin on the uterus and oviduct in mice exposed to nicotine. Adult female mice (n=32 were divided into four groups. Group A: control animals received normal saline, Group B: injected with nicotine 40 μg/kg, Group C: injected with melatonin 10 μg, Group D: injected with nicotine 40 μg/kg and melatonin 10 μg. All animals were treated over 15 days intraperitoneally. On the 16th day, animals in the estrus phase were dissected and their uterus and oviducts were removed. Immunohistochemistry was recruited for studying apoptosis and for detection of estrogen receptor (ER alpha in luminal epithelium of the uterus and oviduct. Enzyme-linked immunosorbent assay was used for serum estradiol level determination. Nicotine in group B decreased estradiol level and ERalpha numbers both in the uterus and oviduct (p<0.05. Co-administration of melatonin-nicotine in Group D ameliorated the histology of the uterus and oviduct, increased ERalpha numbers and reduced apoptosis in the uterus and oviduct compared with the nicotine Group B (p<0.05. This study indicates that nicotine impairs the histology of the uterus and oviduct and co-administration of melatonin-nicotine ameliorates these findings, partly through alteration in ERalpha numbers and reduction of apoptosis

  18. Effect Of Nicotine And Tobacco Consumption On Brain Acetyl ...

    African Journals Online (AJOL)

    The effect of nicotine and tobacco consumption on brain acetyl cholinesterase and serum alkaline phosphatase in rats was studied. Rats were divided into three groups and the first group was fed rat chow and water ad libitum and an oral administration of 2ml of 0.1%(v/v) nicotine per 100g body weight of rats per day.

  19. 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.

  20. Adrenergic Component of Nicotine Antinociception in Rats | Ibironke ...

    African Journals Online (AJOL)

    African Journal of Biomedical Research ... Abstract. It has been widely established that nicotine , the active pharmacological agent in tobacco has antinociceptive effects , but the mechanism of this activity is yet to be fully ... These findings suggest the involvement of the adrenergic system in nicotine induced antinociception .

  1. A Critical Evaluation of Nicotine Replacement Therapy for Teenage Smokers.

    Science.gov (United States)

    Patten, Christi A.

    2000-01-01

    Evaluates the appropriateness and feasibility of nicotine replacement therapy (NRT) in teenage smokers. Available forms of NRT, theoretical rationale and efficacy of NRT, ethical considerations, and the feasibility of NRT in teenage smokers are addressed. Several characteristics similar to adult nicotine dependent smokers have been found in teen…

  2. 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

  3. Nicotine affects protein complex rearrangement in Caenorhabditis elegans cells.

    Science.gov (United States)

    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.

  4. Pulse radiolysis study on aqueous solution of nicotine

    International Nuclear Information System (INIS)

    Wang Shilong; Mei Wang; Ni Yaming; Yao Side; Wang Wenfeng

    2004-01-01

    Nicotine has been studied for the first time by pulse radiolysis techniques. It has been found that hydrated electrons, hydrogen radicals and hydroxyl radicals can react with nicotine to produce anion radicals and neutral radicals, respectively, and the related rate constants have been determined. (authors)

  5. Protective Effect of Vitamin E on Nicotine Induced Reproductive ...

    African Journals Online (AJOL)

    The current study assessed the protective role of vitamin E in alleviating the detrimental effect of nicotine on reproductive functions in male rats. Twenty four male albino rats were divided into four groups of six rats. Control group was treated orally with 1.1 ml/kg body weight normal saline, nicotine treated group received 1.0 ...

  6. The role of adrenergic receptors in nicotine-induced hyperglycemia ...

    African Journals Online (AJOL)

    The role of adrenergic receptors in nicotine-induced hyperglycaemia has not been well studied in amphibians. Thus, this study investigates the effects of alpha and beta adrenergic receptor blockers in nicotine-induced hyperglycaemia in the common African toad Bufo regularis. Toads fasted for 24 h were anaesthetized with ...

  7. Voltammetric determination of nicotine in cigarette tobacco at ...

    African Journals Online (AJOL)

    The electrochemical behavior of nicotine was investigated using cyclic and square wave voltammetric techniques. Electrochemical activation of glassy carbon electrode significantly increased the oxidation peak current of nicotine compared to the bare glassy carbon. At the activated glassy carbon electrode, the square ...

  8. Effect Of Nicotine Administration On Weight And Histology Of Some ...

    African Journals Online (AJOL)

    Summary: It has been emphasized that cigarette smoking is not always synonymous with nicotine administration but the toxic effect of cigarette has often been associated with the nicotine content in cigarette. Epidemiologic studies have clearly indicated that cigarette smoking have many deleterious effects on visceral ...

  9. 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.

  10. 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

  11. Racial differences in hair nicotine concentrations among smokers.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  13. The Activity and Enthalpy of Vaporization of Nicotine from Tobacco at Moderate Temperatures

    Directory of Open Access Journals (Sweden)

    St.Charles F. Kelley

    2016-01-01

    Full Text Available The vapor pressure of nicotine has been reported for unprotonated nicotine and for nicotine-water solutions. Yet no published values exist for nicotine in any commercially relevant matrix or for protonated forms (e.g., tobacco, smoke, electronic cigarette solutions, nicotine replacement products, nicotine salts. Therefore a methodology was developed to measure nicotine activity (defined as the vapor pressure from a matrix divided by the vapor pressure of pure nicotine. The headspace concentration of nicotine was measured for pure nicotine and tobacco stored at 23, 30, and 40 °C which allowed for conversion to vapor pressure and nicotine activity and for the estimation of enthalpy of vaporization. Burley, Flue-cured, Oriental, and cigarette blends were tested. Experiments were conducted with pure nicotine initially until the storage and sampling techniques were validated by comparison with previously published values. We found that the nicotine activity from tobacco was less than 1% with Burley > Flue-cured > Oriental. At 23 °C the nicotine vapor pressure averaged by tobacco type was 0.45 mPa for Oriental tobacco, 1.8 mPa for Flue-cured, 13 mPa for Burley while pure nicotine was 2.95 Pa. In general, the nicotine activity increased as the (calculated unprotonated nicotine concentration increased. The nicotine enthalpy of vaporization from tobacco ranged from 77 kJ/mol to 92 kJ/mol with no obvious trends with regard to tobacco origin, type, stalk position or even the wide range of nicotine activity. The mean value for all tobacco types was 86.7 kJ/mol with a relative standard deviation of 6.5% indicating that this was an intrinsic property of the nicotine form in tobacco rather than the specific tobacco properties. This value was about 30 kJ/mol greater than that of pure nicotine and is similar to the energy needed to remove a proton from monoprotonated nicotine.

  14. T100. NICOTINE USE IMPACTS NEGATIVE SYMPTOMS SEVERITY IN SCHIZOPHRENIA

    Science.gov (United States)

    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

  15. E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices.

    Science.gov (United States)

    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.

  16. Nicotinic mechanisms influencing synaptic plasticity in the hippocampus

    Institute of Scientific and Technical Information of China (English)

    Andon Nicholas PLACZEK; Tao A ZHANG; John Anthony DANI

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the hippocampus, and nicotinic signaling plays an important role in neuronal function. In the context of learning and memory related behaviors associated with hippocampal function, a potentially significant feature of nAChR activity is the impact it has on synaptic plasticity. Synaptic plasticity in hippocampal neurons has long been considered a contributing cellular mechanism of learning and memory. These same kinds of cellular mechanisms are a factor in the development of nicotine addiction. Nicotinic signaling has been demonstrated by in vitro studies to affect synaptic plasticity in hippocampal neurons via multiple steps, and the signaling has also been shown to evoke synaptic plasticity in vivo. This review focuses on the nAChRs subtypes that contribute to hippocampal synaptic plasticity at the cellular and circuit level. It also considers nicotinic influences over long-term changes in the hippocampus that may contribute to addiction.

  17. Expression and function of nicotinic acetylcholine receptors in stem cells

    Directory of Open Access Journals (Sweden)

    Herman S. Cheung

    2016-07-01

    Full Text Available Nicotinic acetylcholine receptors are prototypical ligand gated ion channels typically found in muscular and neuronal tissues. Functional nicotinic acetylcholine receptors, however, have also recently been identified on other cell types, including stem cells. Activation of these receptors by the binding of agonists like choline, acetylcholine, or nicotine has been implicated in many cellular changes. In regards to stem cell function, nicotinic acetylcholine receptor activation leads to changes in stem cell proliferation, migration and differentiation potential. In this review we summarize the expression and function of known nicotinic acetylcholine receptors in different classes of stem cells including: pluripotent stem cells, mesenchymal stem cells, periodontal ligament derived stem cells, and neural progenitor cells and discuss the potential downstream effects of receptor activation on stem cell function.

  18. Functional interaction between Lypd6 and nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Arvaniti, Maria; Jensen, Majbrit M; Soni, Neeraj

    2016-01-01

    Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. Here, we report for the first time a direct interaction of the Lynx protein LY6/PLAUR domain-containing 6 (Lypd6) with n...... brain. Additionally, soluble recombinant Lypd6 protein attenuates nicotine-induced hippocampal inward currents in rat brain slices and decreases nicotine-induced extracellular signal-regulated kinase phosphorylation in PC12 cells, suggesting that binding of Lypd6 is sufficient to inhibit n......AChR-mediated intracellular signaling. We further show that perinatal nicotine exposure in rats (4 mg/kg/day through minipumps to dams from embryonic day 7 to post-natal day 21) significantly increases Lypd6 protein levels in the hippocampus in adulthood, which did not occur after exposure to nicotine in adulthood only. Our...

  19. Revisiting nicotine's role in the ageing brain and cognitive impairment

    DEFF Research Database (Denmark)

    Majdi, Alireza; Kamari, Farzin; Vafaee, Manouchehr Seyedi

    2017-01-01

    stress, excitotoxicity, amyloid-β toxicity, apoptosis, neuroinflammation, and perturb neurotrophic factors in the brain. Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening...... in age-related changes in diverse molecular pathways leading to pathology. Although nicotine has therapeutic potential, paradoxical effects have been reported, possibly due to its inverted U-shape dose-response effects or pharmacokinetic factors. Additionally, nicotine administration should result...... in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment....

  20. 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....

  1. 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)

  2. 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.

  3. Serotonergic modulation of nicotine-induced kinetic tremor in mice.

    Science.gov (United States)

    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.

  4. Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

    Science.gov (United States)

    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

  5. 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.

  6. 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.

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

    Science.gov (United States)

    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.

  8. Inward Rectifier K+ Currents Are Regulated by CaMKII in Endothelial Cells of Primarily Cultured Bovine Pulmonary Arteries.

    Science.gov (United States)

    Qu, Lihui; Yu, Lei; Wang, Yanli; Jin, Xin; Zhang, Qianlong; Lu, Ping; Yu, Xiufeng; Zhong, Weiwei; Zheng, Xiaodong; Cui, Ningren; Jiang, Chun; Zhu, Daling

    2015-01-01

    Endothelium lines the interior surface of vascular walls and regulates vascular tones. The endothelial cells sense and respond to chemical and mechanical stimuli in the circulation, and couple the stimulus signals to vascular smooth muscles, in which inward rectifier K+ currents (Kir) play an important role. Here we applied several complementary strategies to determine the Kir subunit in primarily cultured pulmonary arterial endothelial cells (PAECs) that was regulated by the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). In whole-cell voltage clamp, the Kir currents were sensitive to micromolar concentrations of extracellular Ba2+. In excised inside-out patches, an inward rectifier K+ current was observed with single-channel conductance 32.43 ± 0.45 pS and Popen 0.27 ± 0.04, which were consistent with known unitary conductance of Kir 2.1. RT-PCR and western blot results showed that expression of Kir 2.1 was significantly stronger than that of other subtypes in PAECs. Pharmacological analysis of the Kir currents demonstrated that insensitivity to intracellular ATP, pinacidil, glibenclamide, pH, GDP-β-S and choleratoxin suggested that currents weren't determined by KATP, Kir2.3, Kir2.4 and Kir3.x. The currents were strongly suppressed by exposure to CaMKII inhibitor W-7 and KN-62. The expression of Kir2.1 was inhibited by knocking down CaMKII. Consistently, vasodilation was suppressed by Ba2+, W-7 and KN-62 in isolated and perfused pulmonary arterial rings. These results suggest that the PAECs express an inward rectifier K+ current that is carried dominantly by Kir2.1, and this K+ channel appears to be targeted by CaMKII-dependent intracellular signaling systems.

  9. Inward Rectifier K+ Currents Are Regulated by CaMKII in Endothelial Cells of Primarily Cultured Bovine Pulmonary Arteries.

    Directory of Open Access Journals (Sweden)

    Lihui Qu

    Full Text Available Endothelium lines the interior surface of vascular walls and regulates vascular tones. The endothelial cells sense and respond to chemical and mechanical stimuli in the circulation, and couple the stimulus signals to vascular smooth muscles, in which inward rectifier K+ currents (Kir play an important role. Here we applied several complementary strategies to determine the Kir subunit in primarily cultured pulmonary arterial endothelial cells (PAECs that was regulated by the Ca2+/calmodulin (CaM-dependent protein kinase II (CaMKII. In whole-cell voltage clamp, the Kir currents were sensitive to micromolar concentrations of extracellular Ba2+. In excised inside-out patches, an inward rectifier K+ current was observed with single-channel conductance 32.43 ± 0.45 pS and Popen 0.27 ± 0.04, which were consistent with known unitary conductance of Kir 2.1. RT-PCR and western blot results showed that expression of Kir 2.1 was significantly stronger than that of other subtypes in PAECs. Pharmacological analysis of the Kir currents demonstrated that insensitivity to intracellular ATP, pinacidil, glibenclamide, pH, GDP-β-S and choleratoxin suggested that currents weren't determined by KATP, Kir2.3, Kir2.4 and Kir3.x. The currents were strongly suppressed by exposure to CaMKII inhibitor W-7 and KN-62. The expression of Kir2.1 was inhibited by knocking down CaMKII. Consistently, vasodilation was suppressed by Ba2+, W-7 and KN-62 in isolated and perfused pulmonary arterial rings. These results suggest that the PAECs express an inward rectifier K+ current that is carried dominantly by Kir2.1, and this K+ channel appears to be targeted by CaMKII-dependent intracellular signaling systems.

  10. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

  11. Deconstructing continuous flash suppression

    OpenAIRE

    Yang, Eunice; Blake, Randolph

    2012-01-01

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

  12. Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells

    NARCIS (Netherlands)

    Benyó, Zoltán; Gille, Andreas; Bennett, Clare L.; Clausen, Björn E.; Offermanns, Stefan

    2006-01-01

    The antidyslipidemic drug nicotinic acid (niacin) has been used for decades. One of the major problems of the therapeutical use of nicotinic acid is a strong cutaneous vasodilation called flushing, which develops in almost every patient taking nicotinic acid. Nicotinic acid-induced flushing has been

  13. Case report: Two severe cases of suicide attempts using nicotine containing e-cigarette liquid.

    Science.gov (United States)

    Jalkanen, Ville; Värelä, Ville; Kalliomäki, Jari

    The use of electronic cigarettes and nicotine-containing liquids is getting more common, thus increasing the risk for intentional or unintentional nicotine poisoning. The results of ingestion of nicotine can be severe, even fatal. We describe two different cases of severe poisonings caused by nicotine-containing electronic cigarette liquids.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Electronic nicotine delivery systems: a research agenda.

    Science.gov (United States)

    Etter, Jean-François; Bullen, Chris; Flouris, Andreas D; Laugesen, Murray; Eissenberg, Thomas

    2011-05-01

    Electronic nicotine delivery systems (ENDS, also called electronic cigarettes or e-cigarettes) are marketed to deliver nicotine and sometimes other substances by inhalation. Some tobacco smokers report that they used ENDS as a smoking cessation aid. Whether sold as tobacco products or drug delivery devices, these products need to be regulated, and thus far, across countries and states, there has been a wide range of regulatory responses ranging from no regulation to complete bans. The empirical basis for these regulatory decisions is uncertain, and more research on ENDS must be conducted in order to ensure that the decisions of regulators, health care providers and consumers are based on science. However, there is a dearth of scientific research on these products, including safety, abuse liability and efficacy for smoking cessation. The authors, who cover a broad range of scientific expertise, from basic science to public health, suggest research priorities for non-clinical, clinical and public health studies. They conclude that the first priority is to characterize the safety profile of these products, including in long-term users. If these products are demonstrated to be safe, their efficacy as smoking cessation aids should then be tested in appropriately designed trials. Until these studies are conducted, continued marketing constitutes an uncontrolled experiment and the primary outcome measure, poorly assessed, is user health. Potentially, this research effort, contributing to the safety and efficacy of new smoking cessation devices and to the withdrawal of dangerous products, could save many lives.

  16. The α7 nicotinic acetylcholine receptor complex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Mikkelsen, Jens D

    2012-01-01

    The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds and prote......The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds...... in diseases such as schizophrenia and Alzheimer's disease. Furthermore, α7 nAChR agonists and allosteric modulators differentially alter expression and functionality of the α7 nAChR with repeated administration, which suggests that there may be fundamentally different outcomes of long-term administration...... with these different types of compounds. Finally, we describe the special case of Aβ1-42 binding to the α7 nAChR, which may pose a unique challenge to drug development of α7 nAChR-specific ligands for Alzheimer's disease. Hopefully, a greater knowledge of the many factors influencing α7 nAChR function as well...

  17. Genetic and pharmacokinetic determinants of response to transdermal nicotine in white, black, and Asian nonsmokers.

    Science.gov (United States)

    Dempsey, D A; St Helen, G; Jacob, P; Tyndale, R F; Benowitz, N L

    2013-12-01

    The aim of the study was to examine genetic, pharmacokinetic, and demographic factors that influence sensitivity to nicotine in never-smokers. Sixty never-smokers, balanced for gender and race (white, black, and Asian), wore 7-mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.

  18. Menthol's potential effects on nicotine dependence: a tobacco industry perspective.

    Science.gov (United States)

    Yerger, Valerie B

    2011-05-01

    To examine what the tobacco industry knows about the potential effects menthol may have on nicotine dependence. A snowball strategy was used to systematically search the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu/) between 22 February and 29 April, 2010. Of the approximately 11 million documents available in the Legacy Tobacco Documents Library, the iterative searches returned tens of thousands of results. We qualitatively analysed a final collection of 309 documents relevant the effects of menthol on nicotine dependence. The tobacco industry knows that menthol overrides the harsh taste of tobacco and alleviates nicotine's irritating effects, synergistically interacts with nicotine, stimulates the trigeminal nerve to elicit a 'liking' response for a tobacco product, and makes low tar, low nicotine tobacco products more acceptable to smokers than non-mentholated low delivery products. Menthol is not only used in cigarettes as a flavour additive; tobacco companies know that menthol also has sensory effects and interacts with nicotine to produce tobacco products that are easier to smoke, thereby making it easier to expose smokers, especially those who are new and uninitiated, to the addictive power of nicotine.

  19. Global actions of nicotine on the striatal microcircuit

    Directory of Open Access Journals (Sweden)

    Victor E Plata

    2013-11-01

    Full Text Available The question to solve in the present work is: 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.

  20. 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.

  1. 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.

  2. Adverse effects of perinatal nicotine exposure on reproductive outcomes.

    Science.gov (United States)

    Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

    2015-12-01

    Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

  3. 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.

  4. 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.

  5. Nicotine Enhances Interspecies Relationship between Streptococcus mutans and Candida albicans.

    Science.gov (United States)

    Liu, Shiyu; Qiu, Wei; Zhang, Keke; Zhou, Xuedong; Ren, Biao; He, Jinzhi; Xu, Xin; Cheng, Lei; Li, Mingyun

    2017-01-01

    Streptococcus mutans and Candida albicans are common microorganisms in the human oral cavity. The synergistic relationship between these two species has been deeply explored in many studies. In the present study, the effect of alkaloid nicotine on the interspecies between S. mutans and C. albicans is explored. We developed a dual-species biofilm model and studied biofilm biomass, biofilm structure, synthesis of extracellular polysaccharides (EPS), and expression of glucosyltransferases (Gtfs). Biofilm formation and bacterial and fungal cell numbers in dual-species biofilms increased in the presence of nicotine. More C. albicans cells were present in the dual-species biofilms in the nicotine-treated groups as determined by scanning electron microscopy. The synthesis of EPS was increased by 1 mg/ml of nicotine as detected by confocal laser scanning microscopy. The result of qRT-PCR showed gtfs expression was upregulated when 1 mg/ml of nicotine was used. We speculate that nicotine promoted the growth of S. mutans , and more S. mutans cells attracted more C. albicans cells due to the interaction between two species. Since S. mutans and C. albicans are putative pathogens for dental caries, the enhancement of the synergistic relationship by nicotine may contribute to caries development in smokers.

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

    Science.gov (United States)

    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

  7. Large-scale brain network coupling predicts acute nicotine abstinence effects on craving and cognitive function.

    Science.gov (United States)

    Lerman, Caryn; Gu, Hong; Loughead, James; Ruparel, Kosha; Yang, Yihong; Stein, Elliot A

    2014-05-01

    Interactions of large-scale brain networks may underlie cognitive dysfunctions in psychiatric and addictive disorders. To test the hypothesis that the strength of coupling among 3 large-scale brain networks--salience, executive control, and default mode--will reflect the state of nicotine withdrawal (vs smoking satiety) and will predict abstinence-induced craving and cognitive deficits and to develop a resource allocation index (RAI) that reflects the combined strength of interactions among the 3 large-scale networks. A within-subject functional magnetic resonance imaging study in an academic medical center compared resting-state functional connectivity coherence strength after 24 hours of abstinence and after smoking satiety. We examined the relationship of abstinence-induced changes in the RAI with alterations in subjective, behavioral, and neural functions. We included 37 healthy smoking volunteers, aged 19 to 61 years, for analyses. Twenty-four hours of abstinence vs smoking satiety. Inter-network connectivity strength (primary) and the relationship with subjective, behavioral, and neural measures of nicotine withdrawal during abstinence vs smoking satiety states (secondary). The RAI was significantly lower in the abstinent compared with the smoking satiety states (left RAI, P = .002; right RAI, P = .04), suggesting weaker inhibition between the default mode and salience networks. Weaker inter-network connectivity (reduced RAI) predicted abstinence-induced cravings to smoke (r = -0.59; P = .007) and less suppression of default mode activity during performance of a subsequent working memory task (ventromedial prefrontal cortex, r = -0.66, P = .003; posterior cingulate cortex, r = -0.65, P = .001). Alterations in coupling of the salience and default mode networks and the inability to disengage from the default mode network may be critical in cognitive/affective alterations that underlie nicotine dependence.

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

    Science.gov (United States)

    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.

  9. 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

    Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

  10. Nicotine and Cotinine Levels With Electronic Cigarette: A Review.

    Science.gov (United States)

    Marsot, A; Simon, N

    2016-01-01

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

  11. Nicotine and Cotinine Exposure from Electronic Cigarettes: A Population Approach

    Science.gov (United States)

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

    2015-01-01

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

  12. Nicotine inhibits potassium currents in Aplysia bag cell neurons

    Science.gov (United States)

    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

  13. Pharmacokinetic characterization of three novel 4-mg nicotine lozenges
.

    Science.gov (United States)

    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.
.

  14. Physical and psychological nicotine dependence in Greeks: an epidemiological study.

    Science.gov (United States)

    Margaritis, Vasileios; Mamai-Homata, Eleni

    2010-01-01

    Smoking is the most widespread addictive behaviour in the world, as it causes physical and psychological dependence on nicotine. The objective of the present study was to discern the prevalence and the relative risks of nicotine dependence of adult people in Athens, Greece, as this country holds first place in cigarette consumption in the European Union. A random sample of 202 current smokers (82 men and 120 women) was drawn from residents aged v 18 years in Athens, the capital of Greece. A questionnaire on the physical (Fagerstrom Test of Nicotine Dependence) and psychological (American Psychiatric Association's diagnostic criteria of nicotine abuse) nicotine dependence was used. According to the results of the present study, 12.4% of the sample reported null physical nicotine dependence, and 31.7% had low, 25.7% had moderate and 30.2% had high nicotine dependence. Multiple logistic regression analysis revealed that younger people (aged 18 to 24 and 25 to 34, odds ratio [OR] = 0.047, P physical dependence. Women tended to be systematically less dependent than men (25% and 37.8% high dependence, respectively). Furthermore, 75.7% of the sample had psychological nicotine dependence. Binary logistic regression analysis and chi-square test revealed that younger people (18- to 24-year-olds, OR = 0.081, P dependence. In addition, women showed a higher percentage of withdrawal symptoms compared with men (80% and 68%, respectively). The results of the present study provided compelling evidence that physical and, in particular, psychological nicotine dependence of adult people in Athens, Greece, was significant, and this calls for a course of action that should be taken by public health policy-makers to reduce smoke consumption.

  15. Design, formulation and evaluation of nicotine chewing gum.

    Science.gov (United States)

    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.

  16. 29 CFR 780.607 - “Primarily employed” in agriculture.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false âPrimarily employedâ in agriculture. 780.607 Section 780... AGRICULTURE, PROCESSING OF AGRICULTURAL COMMODITIES, AND RELATED SUBJECTS UNDER THE FAIR LABOR STANDARDS ACT Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements...

  17. 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

  18. Differential Effects of Nicotine on Discrete Components of Visual Attention

    DEFF Research Database (Denmark)

    Vangkilde, Signe Allerup; Bundesen, Claus; Coull, Jennifer T.

    2009-01-01

    or a placebo gum. The experimental paradigm was a letter recognition task with varied stimulus durations terminated by pattern masks. The temporal threshold of conscious perception (t0), visual processing speed (C), storage capacity of visual short-term memory (K), and attentional selectivity (alpha) were...... encoding of information into visual short-term memory is begun, but (b) decreases the rate of encoding and possibly also the attentional selectivity.......Objective: Nicotine is an important cholinergic neurotransmitter that has been linked to various cognitive functions. Several studies have observed attentional modulations after nicotine, but the roles played by nicotine and other cholinergic substances in attention remain unclear. The aim...

  19. 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

  20. Fast simultaneous analysis of caffeine, trigonelline, nicotinic acid and sucrose in coffee by liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Perrone, Daniel; Donangelo, Carmen Marino; Farah, Adriana

    2008-10-15

    A rapid liquid chromatography-mass spectrometry method for the simultaneous quantification of caffeine, trigonelline, nicotinic acid and sucrose in coffee was developed and validated. The method involved extraction with hot water, clarification with basic lead acetate and membrane filtration, followed by chromatographic separation using a Spherisorb(®) S5 ODS2, 5μm chromatographic column and gradient elution with 0.3% aqueous formic acid/methanol at a flow rate of 0.2mL/min. The electrospray ionization source was operated in the negative mode to generate sucrose ions and in the positive mode to generate caffeine, trigonelline and nicotinic acid ions. Ionization suppression of all analytes was found due to matrix effect. Calibrations curves prepared in green and roasted coffee extracts were linear with r(2)>0.999. Roasted coffee was spiked and recoveries ranged from 93.0% to 105.1% for caffeine, from 85.2% to 116.2% for trigonelline, from 89.6% to 113.5% for nicotinic acid and from 94.1% to 109.7% for sucrose. Good repeatibilities (RSDcoffee samples (regular or decaffeinated green, ground roasted and instant) gave results in agreement with the literature. The method showed to be suitable for different types of coffee available in the market thus appearing as a fast and reliable alternative method to be used for routine coffee analysis. Copyright © 2008 Elsevier Ltd. All rights reserved.

  1. Impulsive behavior and nicotinic acetylcholine receptors.

    Science.gov (United States)

    Ohmura, Yu; Tsutsui-Kimura, Iku; Yoshioka, Mitsuhiro

    2012-01-01

    Higher impulsivity is thought to be a risk factor for drug addiction, criminal involvement, and suicide. Excessive levels of impulsivity are often observed in several psychiatric disorders including attention-deficit/hyperactivity disorder and schizophrenia. Previous studies have demonstrated that nicotinic acetylcholine receptors (nAChRs) are involved in impulsive behavior. Here, we introduce recent advances in this field and describe the role of the following nAChR-related brain mechanisms in modulating impulsive behavior: dopamine release in the ventral striatum; α4β2 nAChRs in the infralimbic cortex, which is a ventral part of the medial prefrontal cortex (mPFC); and dopamine release in the mPFC. We also suggest several potential therapeutic drugs to address these mechanisms in impulsivity-related disorders and explore future directions to further elucidate the roles of central nAChRs in impulsive behavior.

  2. 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....

  3. Protective Effect of Vitamin E on Nicotine Induced Reproductive ...

    African Journals Online (AJOL)

    Protective Effect of Vitamin E on Nicotine Induced Reproductive Toxicity in ... The health implications of cigarette smoking and ..... toxic byproducts of many metabolic processes in ... Male infertility, clinical ... rats: A possible role of cessation.

  4. Being a long-term user of nicotine replacement therapy

    DEFF Research Database (Denmark)

    Borup, Gitte; Nørgaard, Lotte Stig; Tønnesen, Philip

    Background During recent years a gradual shift in the application of nicotine replacement therapy (NRT) has taken place from NRT-products only being recommended to achieve smoking cessation, to now including smoking reduction, and long-term substitution of tobacco with NRT has taken place. This has...... been promoted as a way of achieving harm-reduction in highly nicotine dependent smokers who are unwilling or incapable of quitting all nicotine products, as continued use of NRT is widely accepted as being far less hazardous than continued smoking. To our knowledge no previous research has been done...... of feeling addicted, cost of NRT products and fear of adverse health consequences. Aim of study • To get a thorough understanding of the lived experiences of nicotine dependent long-term NRT users. • To investigate what motivates or discourages quitting NRT. Method Semi-structured interviews with long...

  5. Nicotine dependence, use of illegal drugs and psychiatric morbidity.

    Science.gov (United States)

    Martínez-Ortega, José María; Jurado, Dolores; Martínez-González, Miguel Angel; Gurpegui, Manuel

    2006-09-01

    The purpose of this study was to examine the association of smoking and nicotine dependence with psychiatric morbidity, controlling for the potential confounding effect of smoking on the relationship between the use of other substances and psychiatric morbidity. A sample of 290 adults were interviewed at a primary health centre (patients, 58%; patients' relatives, 34%; staff, 8%) to inquire about their tobacco, caffeine, alcohol, and illegal drug consumption. Psychiatric morbidity, defined by a score >6 on the General Health Questionnaire (GHQ-28), showed a strong direct association with nicotine dependence. The use of illegal drugs, but not of alcohol, was also strongly associated with psychiatric morbidity, after controlling for smoking. Both smoking and high nicotine dependence were also associated with use of caffeine, alcohol, cannabis and cocaine. High nicotine dependence may be considered as an expression of individual psychopathologic vulnerability. Tobacco may have a central facilitating role in the use of caffeine, alcohol, and illegal drug.

  6. Hydrogen peroxide production is not primarily increased in human myotubes established from type 2 diabetic subjects.

    Science.gov (United States)

    Minet, A D; Gaster, M

    2011-09-01

    Increased oxidative stress and mitochondrial dysfunction have been implicated in the development of insulin resistance in type 2 diabetes. To date, it is unknown whether increased mitochondrial reactive oxygen species (ROS) production in skeletal muscle from patients with type 2 diabetes is primarily increased or a secondary adaptation to environmental, lifestyle, and hormonal factors. This study investigates whether ROS production is primarily increased in isolated diabetic myotubes. Mitochondrial membrane potential, hydrogen peroxide (H(2)O(2)), superoxide, and mitochondrial mass were determined in human myotubes precultured under normophysiological conditions. Furthermore, the corresponding ATP synthesis was measured in isolated mitochondria. Muscle biopsies were taken from 10 lean subjects, 10 obese subjects, and 10 subjects with type 2 diabetes; satellite cells were isolated, cultured, and differentiated to myotubes. Mitochondrial mass, membrane potential/mitochondrial mass, and superoxide-production/mitochondrial mass were not different between groups. In contrast, H(2)O(2) production/mitochondrial mass and ATP production were significantly reduced in diabetic myotubes compared to lean controls (P production is not primarily increased in diabetic myotubes but rather is reduced. Moreover, the comparable ATP/H(2)O(2) ratios indicate that the reduced ROS production in diabetic myotubes parallels the reduced ATP production because ROS production in diabetic myotubes must be considered to be in a proportion comparable to lean. Thus, the increased ROS production seen in skeletal muscle of type 2 diabetic patients is an adaptation to the in vivo conditions.

  7. 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.

  8. Innate Immunity and Inflammation Post-Stroke: An α7-Nicotinic Agonist Perspective

    Directory of Open Access Journals (Sweden)

    Silke Neumann

    2015-12-01

    Full Text Available Stroke is one of the leading causes of death and long-term disability, with limited treatment options available. Inflammation contributes to damage tissue in the central nervous system across a broad range of neuropathologies, including Alzheimer’s disease, pain, Schizophrenia, and stroke. While the immune system plays an important role in contributing to brain damage produced by ischemia, the damaged brain, in turn, can exert a powerful immune-suppressive effect that promotes infections and threatens the survival of stroke patients. Recently the cholinergic anti-inflammatory pathway, in particular its modulation using α7-nicotinic acetylcholine receptor (α7-nAChR ligands, has shown potential as a strategy to dampen the inflammatory response and facilitate functional recovery in stroke patients. Here we discuss the current literature on stroke-induced inflammation and the effects of α7-nAChR modulators on innate immune cells.

  9. E-Cigarette and Liquid Nicotine Exposures Among Young Children.

    Science.gov (United States)

    Govindarajan, Preethi; Spiller, Henry A; Casavant, Marcel J; Chounthirath, Thitphalak; Smith, Gary A

    2018-04-23

    To investigate exposures to liquid nicotine (including electronic cigarette devices and liquids) among children <6 years old in the United States and evaluate the impact of legislation requiring child-resistant packaging for liquid nicotine containers. Liquid nicotine exposure data from the National Poison Data System for January 2012 through April 2017 were analyzed. There were 8269 liquid nicotine exposures among children <6 years old reported to US poison control centers during the study period. Most (92.5%) children were exposed through ingestion and 83.9% were children <3 years old. Among children exposed to liquid nicotine, 35.1% were treated and released from a health care facility, and 1.4% were admitted. The annual exposure rate per 100 000 children increased by 1398.2% from 0.7 in 2012 to 10.4 in 2015, and subsequently decreased by 19.8% from 2015 to 8.3 in 2016. Among states without a preexisting law requiring child-resistant packaging for liquid nicotine containers, there was a significant decrease in the mean number of exposures during the 9 months before compared with the 9 months after the federal child-resistant packaging law went into effect, averaging 4.4 (95% confidence interval: -7.1 to -1.7) fewer exposures per state after implementation of the law. Pediatric exposures to liquid nicotine have decreased since January 2015, which may, in part, be attributable to legislation requiring child-resistant packaging and greater public awareness of risks associated with electronic cigarette products. Liquid nicotine continues to pose a serious risk for young children. Additional regulation of these products is warranted. Copyright © 2018 by the American Academy of Pediatrics.

  10. Differential sensitivity to nicotine among hypothalamic magnocellular neurons

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Jacobsen, Julie; Kiss, Adrian Emil

    2012-01-01

    The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated...... is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin....

  11. Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes.

    Science.gov (United States)

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

    2016-03-01

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

  12. Emerging nicotine delivery products. Implications for public health.

    Science.gov (United States)

    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.

  13. Skin contamination as pathway for nicotine intoxication in vapers.

    Science.gov (United States)

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

    2017-06-01

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

  14. Nicotine dependence, physical activity, and sedentary behavior among adult smokers

    OpenAIRE

    Paul D Loprinzi; Jerome F Walker

    2015-01-01

    Background: 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. Aim: This study examined the association between nicotine dependence and accelerometer-determined physical activity and sedentary behavior. Materials and Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used....

  15. Probing into the Interaction of Nicotine and Bovine Submaxillary Mucin: NMR, Fluorescence, and FTIR Approaches

    Directory of Open Access Journals (Sweden)

    Xiaoxiang Liao

    2016-01-01

    Full Text Available Nicotine, the important component of cigarette products, may have an impact on the oral environment after inhalation. The research of interaction between nicotine and bovine submaxillary mucin (BSM contributes to understand the binding mechanism of nicotine and BSM, and the effects of nicotine on the structure and function of the mucin. NMR data demonstrated that the interaction between nicotine and BSM did exist, and it was pyrrolidyl ring of nicotine playing the major role in the binding. The quenching mechanisms of nicotine and BSM in different pH were different: for acidic environment, the quenching was dynamic; while it became static in the alkaline circumstance. Synchronous fluorescence spectra indicated that nicotine had effect on the microenvironment of the Trp rather than Tyr residue. Meanwhile, the impact of nicotine on the conformation of BSM was also confirmed by 3D fluorescence and FTIR spectra.

  16. The effect of nicotine on aortic endothelial cell turnover

    International Nuclear Information System (INIS)

    Zimmerman, Matthew; McGeachie, John

    1985-01-01

    Endothelial injury and increased mitotic activity are early features in the pathogenesis of intimal thickening in arteries. This study examines the effect of systemic nicotine on mitotic activity in endothelial cells. Nine adult mice were given nicotine in their drinking water for 5 weeks. The dose (5 mg/kg body wt/day) was equivalent to a human smoking 50-100 cigarettes/day. A group of 8 similar mice, not exposed to nicotine, was the control. At the end of the exposure period all mice were injected with ( 3 H)thymidine (1uCi/g body wt) and were killed 24 h later. After perfusion fixation, en-face preparations of aortic endothelium were processed for autoradiography. In nicotine-affected endothelium 0.46.+-0.11% (SEM) of cells were labeled, which was significantly higher (P<0.01) than in controls (0.14+-0.06). However, there was no difference in cell density between the groups. On this evidence it was concluded that the rate of cell loss, or cell turnover, was greater in nicotine-affected endothelium. Because other studies have shown that increased mitotic acitivity and cell loss are established features of endothelial injury, the present findings provide evidence in support of the hypothesis that nicotine contributes to the pathogenesis of arterial disease in smokers. (author)

  17. The effect of transdermal nicotine patches on sleep and dreams.

    Science.gov (United States)

    Page, F; Coleman, G; Conduit, R

    2006-07-30

    This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models.

  18. Nicotine can skew the characterization of the macrophage type-1 (MΦ1) phenotype differentiated with granulocyte-macrophage colony-stimulating factor to the MΦ2 phenotype

    International Nuclear Information System (INIS)

    Yanagita, Manabu; Kobayashi, Ryohei; Murakami, Shinya

    2009-01-01

    Macrophages (MΦs) exhibit functional heterogeneity and plasticity in the local microenvironment. Recently, it was reported that MΦs can be divided into proinflammatory MΦs (MΦ1) and anti-inflammatory MΦs (MΦ2) based on their polarized functional properties. Here, we report that nicotine, the major ingredient of cigarette smoke, can modulate the characteristics of MΦ1. Granulocyte-macrophage colony-stimulating factor-driven MΦ1 with nicotine (Ni-MΦ1) showed the phenotypic characteristics of MΦ2. Like MΦ2, Ni-MΦ1 exhibited antigen-uptake activities. Ni-MΦ1 suppressed IL-12, but maintained IL-10 and produced high amounts of MCP-1 upon lipopolysaccharide stimulation compared with MΦ1. Moreover, we observed strong proliferative responses of T cells to lipopolysaccharide-stimulated MΦ1, whereas Ni-MΦ1 reduced T cell proliferation and inhibited IFN-γ production by T cells. These results suggest that nicotine can change the functional characteristics of MΦ and skew the MΦ1 phenotype to MΦ2. We propose that nicotine is a potent regulator that modulates immune responses in microenvironments.

  19. Prenatal Exposure to Nicotine and Childhood Asthma: Role of Nicotine Acetylcholine Receptors, Neuropeptides, and Fibronectin Expression in Lung

    National Research Council Canada - National Science Library

    Roman, Jesse

    2005-01-01

    We hypothesize that prenatal exposure to nicotine, a major component of tobacco that transverses the placenta, is largely responsible for the development of asthma in children born of mothers who smoke...

  20. 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.

    Science.gov (United States)

    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.

  1. Nicotine receptor partial agonists for smoking cessation

    Directory of Open Access Journals (Sweden)

    Kate Cahill

    Full Text Available BACKGROUND: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist and reducing smoking satisfaction (acting as an antagonist. OBJECTIVES: The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including cytisine, dianicline and varenicline for smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist' in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, PsycINFO and Web of Science using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialized register was in December 2011. We also searched online clinical trials registers. SELECTION CRITERIA: We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow-up. The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs, using the Mantel-Haenszel fixed-effect model. MAIN RESULTS: Two recent cytisine trials (937 people

  2. Nicotine receptor partial agonists for smoking cessation.

    Science.gov (United States)

    Cahill, Kate; Stead, Lindsay F; Lancaster, Tim

    2012-04-18

    Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including cytisine, dianicline and varenicline for smoking cessation. We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, PsycINFO and Web of Science using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in December 2011. We also searched online clinical trials registers. We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow-up.The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. Two recent cytisine trials (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled RR of

  3. 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.

  4. Withdrawal from Chronic Nicotine Administration Impairs Contextual Fear Conditioning in C57BL/6 Mice

    OpenAIRE

    Davis, Jennifer A.; James, John R.; Siegel, Steven J.; Gould, Thomas J.

    2005-01-01

    The effects of acute nicotine administration (0.09 mg/kg nicotine), chronic nicotine administration (6.3 mg/kg/d nicotine for 14 d), and withdrawal from chronic nicotine administration on fear conditioning in C57BL/6 mice were examined. Mice were trained using two coterminating conditioned stimulus (30 s; 85 dB white noise)– unconditioned stimulus (2 s; 0.57 mA foot shock) pairings and tested 24 h later for contextual and cued fear conditioning. Acute nicotine administration enhanced contextu...

  5. Triacylglycerol Accumulation is not primarily affected in Myotubes established from Type 2 Diabetic Subjects

    DEFF Research Database (Denmark)

    Gaster, Michael; Beck-Nielsen, Henning

    2006-01-01

    In the present study, we investigated triacylglycerol (TAG) accumulation, glucose and fatty acid (FA) uptake, and glycogen synthesis (GS) in human myotubes from healthy, lean, and obese subjects with and without type 2 diabetes (T2D), exposed to increasing palmitate (PA) and oleate (OA...... uptake (P0.05). These results indicate that (1) TAG accumulation is not primarily affected in skeletal muscle tissue of obese and T2D; (2) induced inhibition of oxidative phosphorylation is followed by TAG accumulation...... in skeletal muscle of obese and T2D subjects is adaptive....

  6. Disgust sensitivity is primarily associated with purity-based moral judgments.

    Science.gov (United States)

    Wagemans, Fieke M A; Brandt, Mark J; Zeelenberg, Marcel

    2018-03-01

    Individual differences in disgust sensitivity are associated with a range of judgments and attitudes related to the moral domain. Some perspectives suggest that the association between disgust sensitivity and moral judgments will be equally strong across all moral domains (i.e., purity, authority, loyalty, care, fairness, and liberty). Other perspectives predict that disgust sensitivity is primarily associated with judgments of specific moral domains (e.g., primarily purity). However, no study has systematically tested if disgust sensitivity is associated with moral judgments of the purity domain specifically, more generally to moral judgments of the binding moral domains, or to moral judgments of all of the moral domains equally. Across 5 studies (total N = 1,104), we find consistent evidence for the notion that disgust sensitivity relates more strongly to moral condemnation of purity-based transgressions (meta-analytic r = .40) than to moral condemnation of transgressions of any of the other domains (range meta-analytic rs: .07-.27). Our findings are in line with predictions from Moral Foundations Theory, which predicts that personality characteristics like disgust sensitivity make people more sensitive to a certain set of moral issues. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  7. Lamin A/C mutation affecting primarily the right side of the heart

    Directory of Open Access Journals (Sweden)

    Laura Ollila

    2013-04-01

    Full Text Available LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohisto - chemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories.

  8. 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.

  9. Stimulation of Na+ -K+ -pump currents by epithelial nicotinic receptors in rat colon.

    Science.gov (United States)

    Bader, Sandra; Lottig, Lena; Diener, Martin

    2017-05-01

    Acetylcholine-induced epithelial Cl - secretion is generally thought to be mediated by epithelial muscarinic receptors and nicotinic receptors on secretomotor neurons. However, recent data have shown expression of nicotinic receptors by intestinal epithelium and the stimulation of Cl - secretion by nicotine, in the presence of the neurotoxin, tetrodotoxin. Here, we aimed to identify the transporters activated by epithelial nicotinic receptors and to clarify their role in cholinergic regulation of intestinal ion transport. Ussing chamber experiments were performed, using rat distal colon with intact epithelia. Epithelia were basolaterally depolarized to measure currents across the apical membrane. Apically permeabilized tissue was also used to measure currents across the basolateral membrane in the presence of tetrodotoxin. Nicotine had no effect on currents through Cl - channels in the apical membrane or on currents through K + channels in the apical or the basolateral membrane. Instead, nicotine stimulated the Na + -K + -pump as indicated by Na + -dependency and sensitivity of the nicotine-induced current across the basolateral membrane to cardiac steroids. Effects of nicotine were inhibited by nicotinic receptor antagonists such as hexamethonium and mimicked by dimethyl-4-phenylpiperazinium, a chemically different nicotinic agonist. Simultaneous stimulation of epithelial muscarinic and nicotinic receptors led to a strong potentiation of transepithelial Cl - secretion. These results suggest a novel concept for the cholinergic regulation of transepithelial ion transport by costimulation of muscarinic and nicotinic epithelial receptors and a unique role of nicotinic receptors controlling the activity of the Na + -K + -ATPase. © 2017 The British Pharmacological Society.

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

    Science.gov (United States)

    Lee, Hyunchan; Jang, Minji; Noh, Jihyun

    2017-02-01

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

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

    Science.gov (United States)

    MacQueen, David A; Drobes, David J

    2017-10-01

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

  12. Wild tobacco genomes reveal the evolution of nicotine biosynthesis.

    Science.gov (United States)

    Xu, Shuqing; Brockmöller, Thomas; Navarro-Quezada, Aura; Kuhl, Heiner; Gase, Klaus; Ling, Zhihao; Zhou, Wenwu; Kreitzer, Christoph; Stanke, Mario; Tang, Haibao; Lyons, Eric; Pandey, Priyanka; Pandey, Shree P; Timmermann, Bernd; Gaquerel, Emmanuel; Baldwin, Ian T

    2017-06-06

    Nicotine, the signature alkaloid of Nicotiana species responsible for the addictive properties of human tobacco smoking, functions as a defensive neurotoxin against attacking herbivores. However, the evolution of the genetic features that contributed to the assembly of the nicotine biosynthetic pathway remains unknown. We sequenced and assembled genomes of two wild tobaccos, Nicotiana attenuata (2.5 Gb) and Nicotiana obtusifolia (1.5 Gb), two ecological models for investigating adaptive traits in nature. We show that after the Solanaceae whole-genome triplication event, a repertoire of rapidly expanding transposable elements (TEs) bloated these Nicotiana genomes, promoted expression divergences among duplicated genes, and contributed to the evolution of herbivory-induced signaling and defenses, including nicotine biosynthesis. The biosynthetic machinery that allows for nicotine synthesis in the roots evolved from the stepwise duplications of two ancient primary metabolic pathways: the polyamine and nicotinamide adenine dinucleotide (NAD) pathways. In contrast to the duplication of the polyamine pathway that is shared among several solanaceous genera producing polyamine-derived tropane alkaloids, we found that lineage-specific duplications within the NAD pathway and the evolution of root-specific expression of the duplicated Solanaceae-specific ethylene response factor that activates the expression of all nicotine biosynthetic genes resulted in the innovative and efficient production of nicotine in the genus Nicotiana Transcription factor binding motifs derived from TEs may have contributed to the coexpression of nicotine biosynthetic pathway genes and coordinated the metabolic flux. Together, these results provide evidence that TEs and gene duplications facilitated the emergence of a key metabolic innovation relevant to plant fitness.

  13. The effects of acute nicotine on contextual safety discrimination.

    Science.gov (United States)

    Kutlu, Munir G; Oliver, Chicora; Gould, Thomas J

    2014-11-01

    Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients. © The Author(s) 2014.

  14. 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.

  15. 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.

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

    Science.gov (United States)

    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.

  17. 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

  18. Direct healthcare costs of selected diseases primarily or partially transmitted by water.

    Science.gov (United States)

    Collier, S A; Stockman, L J; Hicks, L A; Garrison, L E; Zhou, F J; Beach, M J

    2012-11-01

    Despite US sanitation advancements, millions of waterborne disease cases occur annually, although the precise burden of disease is not well quantified. Estimating the direct healthcare cost of specific infections would be useful in prioritizing waterborne disease prevention activities. Hospitalization and outpatient visit costs per case and total US hospitalization costs for ten waterborne diseases were calculated using large healthcare claims and hospital discharge databases. The five primarily waterborne diseases in this analysis (giardiasis, cryptosporidiosis, Legionnaires' disease, otitis externa, and non-tuberculous mycobacterial infection) were responsible for over 40 000 hospitalizations at a cost of $970 million per year, including at least $430 million in hospitalization costs for Medicaid and Medicare patients. An additional 50 000 hospitalizations for campylobacteriosis, salmonellosis, shigellosis, haemolytic uraemic syndrome, and toxoplasmosis cost $860 million annually ($390 million in payments for Medicaid and Medicare patients), a portion of which can be assumed to be due to waterborne transmission.

  19. Temporal integration of loudness in listeners with hearing losses of primarily cochlear origin

    DEFF Research Database (Denmark)

    Buus, Søren; Florentine, Mary; Poulsen, Torben

    1999-01-01

    To investigate how hearing loss of primarily cochlear origin affects the loudness of brief tones, loudness matches between 5- and 200-ms tones were obtained as a function of level for 15 listeners with cochlear impairments and for seven age-matched controls. Three frequencies, usually 0.5, 1, and 4...... of temporal integration—defined as the level difference between equally loud short and long tones—varied nonmonotonically with level and was largest at moderate levels. No consistent effect of frequency was apparent. The impaired listeners varied widely, but most showed a clear effect of level on the amount...... of temporal integration. Overall, their results appear consistent with expectations based on knowledge of the general properties of their loudness-growth functions and the equal-loudness-ratio hypothesis, which states that the loudness ratio between equal-SPL long and brief tones is the same at all SPLs...

  20. The Effects of Stress on Levels of Nicotine in the Rat

    Science.gov (United States)

    1990-03-01

    nicotine (Benowitz & Jacob, 1985; Feyerabend & Russell, 1978; Fix, Daughton & Issenberg, 1986; Matsukura, Sakamoto, Takahashi, Matsuyama...circulating levels of nicotine ( Feyerabend & Russell, 1978; Rosenberg, Benowitz, Jacob & Wilson, 1980). These studies suggest that acidification of

  1. Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats

    Directory of Open Access Journals (Sweden)

    Negin Noori

    2014-01-01

    Conclusion: This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

  2. Nicotine patches improve mood and response speed in a lexical decision task.

    Science.gov (United States)

    Gentry, M V; Hammersley, J J; Hale, C R; Nuwer, P K; Meliska, C J

    2000-01-01

    The effects of smoking a cigarette or wearing a transdermal nicotine patch on mood and lexical decision-making were tested in eight smokers. Each participant was tested after 4 hours of smoking abstinence, under 4 conditions: placebo (very low nicotine) cigarette, nicotine cigarette, placebo patch, and nicotine patch. Relative to placebo, wearing the nicotine patch reduced Profile of Mood States (POMS) Total Mood Disturbance and Fatigue/Inertia scores, while increasing the speed of some types of lexical decisions. Smoking a nicotine cigarette did not affect reaction times, but unexpectedly decreased the accuracy of Word/ Nonword lexical decisions. Thus, transdermal nicotine may improve mood and facilitate longterm memory search and/or attentional processes in nicotine-deprived smokers.

  3. Effect of Nicotine on Cognitive Performance in Non-smokers in a ...

    African Journals Online (AJOL)

    Nicotine was administered via chewing 4 mg nicotine gum for 15 minutes ... state examination MMSE), working memory (Two-back task, reaction time: 1 sec.) ... of the improvements increased significantly with decrease in baseline PS.

  4. Reduced nicotine content cigarettes, e-cigarettes and the cigarette end game

    Science.gov (United States)

    Benowitz, Neal L.; Donny, Eric C.; Hatsukami, Dorothy K.

    2017-01-01

    The reduced nicotine content cigarette and the emergence of non-combusted nicotine products like e-cigarettes should be viewed not as alternatives but as complementary components of regulatory interventions that could virtually end combusted tobacco use. PMID:27555354

  5. The Serotonin Transporter Undergoes Constitutive Internalization and Is Primarily Sorted to Late Endosomes and Lysosomal Degradation*

    Science.gov (United States)

    Rahbek-Clemmensen, Troels; Bay, Tina; Eriksen, Jacob; Gether, Ulrik; Jørgensen, Trine Nygaard

    2014-01-01

    The serotonin transporter (SERT) plays a critical role in regulating serotonin signaling by mediating reuptake of serotonin from the extracellular space. The molecular and cellular mechanisms controlling SERT levels in the membrane remain poorly understood. To study trafficking of the surface resident SERT, two functional epitope-tagged variants were generated. Fusion of a FLAG-tagged one-transmembrane segment protein Tac to the SERT N terminus generated a transporter with an extracellular epitope suited for trafficking studies (TacSERT). Likewise, a construct with an extracellular antibody epitope was generated by introducing an HA (hemagglutinin) tag in the extracellular loop 2 of SERT (HA-SERT). By using TacSERT and HA-SERT in antibody-based internalization assays, we show that SERT undergoes constitutive internalization in a dynamin-dependent manner. Confocal images of constitutively internalized SERT demonstrated that SERT primarily co-localized with the late endosomal/lysosomal marker Rab7, whereas little co-localization was observed with the Rab11, a marker of the “long loop” recycling pathway. This sorting pattern was distinct from that of a prototypical recycling membrane protein, the β2-adrenergic receptor. Furthermore, internalized SERT co-localized with the lysosomal marker LysoTracker and not with transferrin. The sorting pattern was further confirmed by visualizing internalization of SERT using the fluorescent cocaine analog JHC1-64 and by reversible and pulse-chase biotinylation assays showing evidence for lysosomal degradation of the internalized transporter. Finally, we found that SERT internalized in response to stimulation with 12-myristate 13-acetate co-localized primarily with Rab7- and LysoTracker-positive compartments. We conclude that SERT is constitutively internalized and that the internalized transporter is sorted mainly to degradation. PMID:24973209

  6. Coordination Driven Capture of Nicotine Inside a Mesoporous MOF.

    Science.gov (United States)

    Balestri, Davide; Capucci, Davide; Demitri, Nicola; Bacchi, Alessia; Pelagatti, Paolo

    2017-06-30

    Metal organic frameworks (MOFs) are a wide class of crystalline porous polymers studied in many fields, ranging from catalysis to gas storage. In the past few years, MOFs have been studied for the encapsulation of organic or organometallic molecules and for the development of potential drug carriers. Here, we report on the study of two structurally-related mesoporous Cu-MOFs, namely PCN-6 and PCN-6' (PCN stands for Porous Coordination Network), for nicotine trapping. Nicotine is a well-known alkaloid liquid molecule at room temperature, whose crystalline structure is still unknown. In this work, the loading process was monitored by electron ionization mass spectrometry by using a direct insertion probe (DIP-EI/MS), infrared (IR), and ultraviolet/visible (UV/VIS) analysis. Both nuclear magnetic resonance (NMR) spectroscopy and thermogravimetric (TGA) analysis showed evidence that nicotine trapping reaches remarkable uptakes up to 40 wt %. In the case of PCN-6@nicotine, X-ray structural resolution revealed that the guest uptake is triggered by coordination of the pyridine ring of nicotine to the copper nuclei of the paddle-wheel units composing the framework of PCN-6.

  7. E-cigarettes for the management of nicotine addiction

    Directory of Open Access Journals (Sweden)

    Knight-West O

    2016-08-01

    Full Text Available Oliver Knight-West, Christopher Bullen The National Institute for Health Innovation, School of Population Health, The University of Auckland, Auckland, New Zealand Abstract: In this review, we discuss current evidence on electronic cigarettes (ECs, a rapidly evolving class of nicotine delivery system, and their role in managing nicotine addiction, specifically in helping smokers to quit smoking and/or reduce the amount of tobacco they smoke. The current evidence base is limited to three randomized trials (only one compares ECs with nicotine replacement therapy and a growing number of EC user surveys (n=6, case reports (n=4, and cohort studies (n=8. Collectively, these studies suggest modest cessation efficacy and a few adverse effects, at least with the short-term use. On this basis, we provide advice for health care providers on providing balanced information for patients who enquire about ECs. More research, specifically well-conducted large efficacy trials comparing ECs with standard smoking cessation management (eg, nicotine replacement therapy plus behavioral support and long-term prospective studies for adverse events, are urgently needed to fill critical knowledge gaps on these products. Keywords: tobacco, smoking, nicotine, electronic cigarettes, cessation, addiction

  8. Dependence on the nicotine gum in former smokers.

    Science.gov (United States)

    Etter, Jean-François

    2009-03-01

    We conducted an Internet survey in 2004-2007 in 526 daily users of the nicotine gum, to assess use of, and dependence on the nicotine gum in former smokers. We used modified versions of the Nicotine Dependence Syndrome Scale (NDSS-G), the Cigarette Dependence Scale (CDS-G) and the Fagerström Test (FTND-G). After 30 days, 155 participants (29%) indicated their gum use. Higher dependence on the gum predicted a lower chance of stopping using it at follow-up (odds ratio=0.36 for each standard deviation unit on CDS-G, p=0.001). More long-term (>3 months) than short-term (dependence on the gum than short-term users, as assessed with NDSS-Gum, CDS-Gum and FTND-Gum (all pdependence on the nicotine gum. Lower levels of dependence on the gum predicted cessation of gum use. However, long term use of the nicotine gum has no known serious adverse consequence, and may be beneficial if it prevents late relapse.

  9. Antibacterial activity of nicotine and its copper complex

    International Nuclear Information System (INIS)

    Zaidi, M.I.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Cu(II)-nicotine was isolated from leaves of Nicotiana tabacum using metal ions following the method of Munir et al., 1994. Their antibacterial activity against ten different species of gram positive and gram negative bacteria were studied. For comparative study, pure sample of nicotine and metal salts used for complexation; Copper(II) chloride were also subjected to antibacterial tests with the same species of bacteria under similar conditions. Results indicated that nicotine had no effect on all the bacteria tested except Escherichia coli, Pseudomonas aeroginosa and Enterococcus faecalis, which showed 14 mm zone of inhibition at 200 mu g l00 mul/sup -1/ Copper(II) chloride was found to be effective against seven species and ineffective against three species of selected bacteria. On the other hand, Cu(II)-nicotine complex was ineffective against five species of bacteria at lower level while at higher level, only one species of bacteria showed resistance against this complex. The complex was compared with three standard antibiotics. Thus, this complex can be used against a variety of microorganisms at higher level. (author)

  10. Pharmacokinetic Evaluation of Two Nicotine Patches in Smokers.

    Science.gov (United States)

    Rasmussen, Scott; Horkan, Kathleen Halabuk; Kotler, Mitchell

    2018-02-02

    Smoking continues to be a major preventable cause of early mortality worldwide, and nicotine replacement therapy has been demonstrated to increase rates of abstinence among smokers attempting to quit. Nicotine transdermal systems (also known as nicotine patches) attach to the skin via an adhesive layer composed of a mixture of different-molecular-weight polyisobutylenes (PIBs) in a specific ratio. This randomized, single-dose, 2-treatment, crossover pharmacokinetic (PK) trial assessed the bioequivalence of nicotine patches including a replacement PIB adhesive (test) compared with the PIB adhesive historically used on marketed patches (reference). The test and reference patches were bioequivalent, as determined by the PK parameters of C max and AUC 0-t . In addition, the parameters T max and t 1/2 did not significantly differ between the 2 patches, supporting the bioequivalence finding from the primary analysis. The tolerability profiles of the patches containing the replacement and previously used PIB adhesives were similar; application-site adverse events did not significantly differ between test and reference patches. Overall, these data establish the bioequivalence of the nicotine patch with the replacement PIB adhesive formulation and the previously utilized PIB adhesive formulation. © 2018 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  11. Race, gender, and nicotine metabolism in adolescent smokers.

    Science.gov (United States)

    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.

  12. Coordination Driven Capture of Nicotine Inside a Mesoporous MOF

    Directory of Open Access Journals (Sweden)

    Davide Balestri

    2017-06-01

    Full Text Available Metal organic frameworks (MOFs are a wide class of crystalline porous polymers studied in many fields, ranging from catalysis to gas storage. In the past few years, MOFs have been studied for the encapsulation of organic or organometallic molecules and for the development of potential drug carriers. Here, we report on the study of two structurally-related mesoporous Cu-MOFs, namely PCN-6 and PCN-6′ (PCN stands for Porous Coordination Network, for nicotine trapping. Nicotine is a well-known alkaloid liquid molecule at room temperature, whose crystalline structure is still unknown. In this work, the loading process was monitored by electron ionization mass spectrometry by using a direct insertion probe (DIP-EI/MS, infrared (IR, and ultraviolet/visible (UV/VIS analysis. Both nuclear magnetic resonance (NMR spectroscopy and thermogravimetric (TGA analysis showed evidence that nicotine trapping reaches remarkable uptakes up to 40 wt %. In the case of PCN-6@nicotine, X-ray structural resolution revealed that the guest uptake is triggered by coordination of the pyridine ring of nicotine to the copper nuclei of the paddle-wheel units composing the framework of PCN-6.

  13. The role of nicotinic acetylcholine and opioid systems of the ventral orbital cortex in modulation of formalin-induced orofacial pain in rats.

    Science.gov (United States)

    Yousofizadeh, Shahnaz; Tamaddonfard, Esmaeal; Farshid, Amir Abbas

    2015-07-05

    Nicotinic acetylcholine and opioid receptors are involved in modulation of pain. In the present study, we investigated the effects of microinjection of nicotinic acetylcholine and opioid compounds into the ventral orbital cortex (VOC) on the formalin-induced orofacial pain in rats. For this purpose, two guide cannulas were placed into the left and right sides of the VOC of the brain. Orofacial pain was induced by subcutaneous injection of a diluted formalin solution (50μl, 1.5%) into the right vibrissa pad and face rubbing durations were recorded at 3-min blocks for 45min. Formalin produced a marked biphasic pain response (first phase: 0-3min and second phase: 15-33min). Epibatidine (a nicotinic receptor agonist) at doses of 0.05, 0.1 and 0.2μg/site, morphine (an opioid receptor agonist) at doses of 0.5, 1 and 2μg/site and their sub-analgesic doses (0.025μg/site epibatidine with 0.25μg/site morphine) combination treatment suppressed the second phase of pain. The antinociceptive effect induced by 0.2μg/site of epibatidine, but not morphine (2μg/site), was prevented by 2μg/site of mecamylamine (a nicotinic receptor antagonist). Naloxone (an opioid receptor antagonist) at a dose of 2μg/site prevented the antinociceptive effects induced by 2μg/site of morphine and 0.2μg/site of epibatidine. No above-mentioned chemical compounds affected locomotor activity. These results showed that at the VOC level, epibatidine and morphine produced antinociception. In addition, opioid receptor might be involved in epibatidine-induced antinociception, but the antinociception induced by morphine was not mediated through nicotinic acetylcholine receptor. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Nicotine in dried boletus mushrooms - Causes for contamination must be determined

    OpenAIRE

    German Federal Institute for Risk Assessment

    2009-01-01

    Recently, nicotine has been detected in samples of dried boletus mushrooms. In large doses, nicotine is a strong neurotoxin and natural component of the tobacco plant. Yet food supply plants such as potatoes, tomatoes, aubergines and cauliflower also contain very small amounts of the substance. The cause of nicotine contamination in dried boletus mushrooms has thus far not been determined since nicotine has not been established as a naturally occurring component in mushrooms. Whether the nico...

  15. Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice.

    Science.gov (United States)

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

    2016-10-01

    Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Sodium fire suppression

    Energy Technology Data Exchange (ETDEWEB)

    Malet, J C [DSN/SESTR, Centre de Cadarache, Saint-Paul-lez-Durance (France)

    1979-03-01

    Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

  17. Sodium fire suppression

    International Nuclear Information System (INIS)

    Malet, J.C.

    1979-01-01

    Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  19. 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)

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

    Science.gov (United States)

    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.

  1. Emergence of dormant conditioned incentive approach by conditioned withdrawal in nicotine addiction.

    Science.gov (United States)

    Scott, Daniel; Hiroi, Noboru

    2010-10-15

    Nicotine is one of the determinants for the development of persistent smoking, and this maladaptive behavior is characterized by many symptoms, including withdrawal and nicotine seeking. The process by which withdrawal affects nicotine seeking is poorly understood. The impact of a withdrawal-associated cue on nicotine (.2 mg/kg)-conditioned place preference was assessed in male C57BL/6J mice (n = 8-17/group). To establish a cue selectively associated with withdrawal distinct from those associated with nicotine, a tone was paired with withdrawal in their home cages; mice were chronically exposed to nicotine (200 μg/mL for 15 days) from drinking water in their home cages and received the nicotinic acetylcholine receptor antagonist mecamylamine (2.5 mg/kg) to precipitate withdrawal in the presence of a tone. The effect of the withdrawal-associated tone on nicotine-conditioned place preference was then evaluated in the place-conditioning apparatus after a delay, when nicotine-conditioned place preference spontaneously disappeared. A cue associated with precipitated withdrawal reactivated the dormant effect of nicotine-associated cues on conditioned place preference. This effect occurred during continuous exposure to nicotine but not during abstinence. A conditioned withdrawal cue could directly amplify the incentive properties of cues associated with nicotine. This observation extends the contemporary incentive account of the role of withdrawal in addiction to cue-cue interaction. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Role of green tea on nicotine toxicity on liver and lung of mice ...

    African Journals Online (AJOL)

    DR_Mohsen

    2012-01-26

    Jan 26, 2012 ... Nicotine is the more abundant component in cigarette smoking. The natural diet contains a variety ... morphometrical methods and study the protective effect of green tea against toxicity of nicotine. Four groups of the male ... nicotine exposure induced oxidative stress and causes histopathological changes ...

  3. Effect of MK-801 on the development of nicotine sensitization of nucleus accumbens dopamine release

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Soo Kyung; Choung, In Soon; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    We have previously found that MK-801, a noncompetitive NMDA receptor antagonist, prevents behavioral sensitization to nicotine. This study aimed to investigate the effect of MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drug on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague-Dawley rats were pretreated with MK-801 (0.3 mg/kg, i.p.) or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for 7 consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens and DA release was monitored using in vivo microdialysis. In rats pretreated with chronic nicotine, local nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response 969 {+-} 235% (mean {+-} SEM) of basal level vs. 520 {+-} 93%, P < 0.05). Co-administration of MK-801 with nicotine attenuated an increase of DA release elicited by local nicotine challenge, compared with nicotine alone (maximal DA response 427 {+-} 83% of basal level vs. 969 {+-} 235%, P < 0.01). These results suggest that MK-801 blocks the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of NMDA receptors in the development of behavioral sensitization to nicotine.

  4. effect of nicotine administration on weight and histology of some vital ...

    African Journals Online (AJOL)

    Daniel Owu

    However it is not certain whether this effect is produced entirely by nicotine as cigarettes contain other toxic ... nicotine treatment while weights of the heart and liver increased with 60days treatment with the appearance of .... carried out in ascending grade of alcohol. .... This study showed that chronic nicotine treatment.

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

    International Nuclear Information System (INIS)

    Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa

    2014-01-01

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

  6. Progressive and Lasting Amplilfication of Accumbal Nicotine-Seeking Neural Signals

    NARCIS (Netherlands)

    Guillem, K.; Peoples, L.L.

    2010-01-01

    Although neuroadaptations in the nucleus accumbens (NAc) are thought to contribute to nicotine addiction, little is known about the chronic effects of nicotine on NAc neuronal activity. In the present experiment, rats were exposed to a 23 d period of nicotine selfadministration (SA), a 30 d

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

    Energy Technology Data Exchange (ETDEWEB)

    Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa, E-mail: ebuszman@sum.edu.pl

    2014-10-15

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

  8. Effect of MK-801 on the development of nicotine sensitization of nucleus accumbens dopamine release

    International Nuclear Information System (INIS)

    Hong, Soo Kyung; Choung, In Soon; Kim, Sang Eun

    2005-01-01

    We have previously found that MK-801, a noncompetitive NMDA receptor antagonist, prevents behavioral sensitization to nicotine. This study aimed to investigate the effect of MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drug on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague-Dawley rats were pretreated with MK-801 (0.3 mg/kg, i.p.) or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for 7 consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens and DA release was monitored using in vivo microdialysis. In rats pretreated with chronic nicotine, local nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response 969 ± 235% (mean ± SEM) of basal level vs. 520 ± 93%, P < 0.05). Co-administration of MK-801 with nicotine attenuated an increase of DA release elicited by local nicotine challenge, compared with nicotine alone (maximal DA response 427 ± 83% of basal level vs. 969 ± 235%, P < 0.01). These results suggest that MK-801 blocks the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of NMDA receptors in the development of behavioral sensitization to nicotine

  9. Key issues surrounding the health impacts of electronic nicotine delivery systems (ENDS) and other sources of nicotine.

    Science.gov (United States)

    Drope, Jeffrey; Cahn, Zachary; Kennedy, Rosemary; Liber, Alex C; Stoklosa, Michal; Henson, Rosemarie; Douglas, Clifford E; Drope, Jacqui

    2017-11-01

    Answer questions and earn CME/CNE Over the last decade, the use of electronic nicotine delivery systems (ENDS), including the electronic cigarette or e-cigarette, has grown rapidly. More youth now use ENDS than any tobacco product. This extensive research review shows that there are scientifically sound, sometimes competing arguments about ENDS that are not immediately and/or completely resolvable. However, the preponderance of the scientific evidence to date suggests that current-generation ENDS products are demonstrably less harmful than combustible tobacco products such as conventional cigarettes in several key ways, including by generating far lower levels of carcinogens and other toxic compounds than combustible products or those that contain tobacco. To place ENDS in context, the authors begin by reviewing the trends in use of major nicotine-containing products. Because nicotine is the common core-and highly addictive-constituent across all tobacco products, its toxicology is examined. With its long history as the only nicotine product widely accepted as being relatively safe, nicotine-replacement therapy (NRT) is also examined. A section is also included that examines snus, the most debated potential harm-reduction product before ENDS. Between discussions of NRT and snus, ENDS are extensively examined: what they are, knowledge about their level of "harm," their relationship to smoking cessation, the so-called gateway effect, and dual use/poly-use. CA Cancer J Clin 2017;67:449-471. © 2017 American Cancer Society. © 2017 American Cancer Society.

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

    Science.gov (United States)

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

    2017-10-01

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

  11. Electronic Nicotine Delivery Systems (ENDS): What Nurses Need to Know.

    Science.gov (United States)

    Essenmacher, Carol; Naegle, Madeline; Baird, Carolyn; Vest, Bridgette; Spielmann, Rene; Smith-East, Marie; Powers, Leigh

    Efforts to decrease adverse effects of tobacco use are affected by emergence of new nicotine delivery products. Advertising, product promotion, and social media promote use of these products, yet a lack of evidence regarding safety leaves nurses unprepared to counsel patients. To critically evaluate current research, reviews of literature, expert opinion, and stakeholder policy proposals on use and safety of electronic nicotine delivery systems (ENDS). A targeted examination of literature generated by key stakeholders and subject matter experts was conducted using key words, modified by risk factors, and limited to the past 8 years. Current knowledge gaps in research literature and practice implications of the literature are discussed. The safety of ENDS is questionable and unclear. There are clear health risks of nicotine exposure to developing brains. Potential health risks of ENDS secondhand emissions exposure exist. Using ENDS to facilitate total tobacco cessation is not proven.

  12. Consumption and foraging behaviors for common stimulants (nicotine, caffeine).

    Science.gov (United States)

    Phillips, James G; Currie, Jonathan; Ogeil, Rowan P

    2016-01-01

    Models are needed to understand the emerging capability to track consumers' movements. Therefore, we examined the use of legal and readily available stimulants that vary in their addictive potential (nicotine, caffeine). One hundred sixty-six participants answered the Kessler Psychological Distress Scale (K10), the Severity of Dependence Scale for nicotine and caffeine, and reported the number of times and locations stimulants were purchased and used. On average, nicotine dependent individuals made their purchases from 2 locations, while caffeine dependent individuals consumed caffeine at 2 locations, but some people exhibited a greater range and intensity of use. Stimulant foraging behavior could be described by power laws, and is exacerbated by dependency. The finding has implications for attempts to control substance use.

  13. First trimester nicotine exposure and the risk of infantile colic

    DEFF Research Database (Denmark)

    Milidou, Ioanna; Henriksen, Tine Brink; Jensen, Morten Søndergaard

    Background: Although prenatal exposure to maternal smoking has been associated with infantile colic (IC), to date no published studies have reported on the relationship between the prenatal use of nicotine replacement therapy (NRT) and IC. Aim: We aimed to assess the relationship between fetal...... exposure to nicotine, coming from both cigarette smoking and use of NRT early in pregnancy, and IC. Methods: The study population consisted of 63,883 pregnancies that resulted in live born singletons enrolled in the Danish National Birth Cohort between 1997 and 2002. Mother’s smoking habits and use of NRT......: The results indicate that prenatal exposure to nicotine from any source during the first trimester of the pregnancy increases the risk of infantile colic....

  14. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.

    Science.gov (United States)

    Stamler, J S; Jaraki, O; Osborne, J; Simon, D I; Keaney, J; Vita, J; Singel, D; Valeri, C R; Loscalzo, J

    1992-01-01

    We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S-nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be

  15. The development and characterization of a primarily mineral calcium phosphate - poly(epsilon-caprolactone) biocomposite

    Science.gov (United States)

    Dunkley, Ian Robert

    Orthopaedic reconstruction often involves the surgical introduction of structural implants that provide for rigid fixation, skeletal stabilization, and bone integration. The high stresses incurred by these implanted devices have historically limited material choices to metallic and select polymeric formulations. While mechanical requirements are achieved, these non-degradable materials do not participate actively in the remodeling of the skeleton and present the possibility of long-term failure or rejection. This is particularly relevant in cervical fusion, an orthopaedic procedure to treat damaged, degenerative or diseased intervertebral discs. A significant improvement on the available synthetic bone replacement/regeneration options for implants to treat these conditions in the cervical spine may be achieved with the development of primarily mineral biocomposites comprised of a bioactive ceramic matrix reinforced with a biodegradable polymer. Such a biocomposite may be engineered to possess the clinically required mechanical properties of a particular application, while maintaining the ability to be remodeled completely by the body. A biocomposite of Si-doped calcium phosphate (Si-CaP) and poly(epsilon-caprolactone) (PCL) was developed for application as such a synthetic bone material for potential use as a fusion device in the cervical spine. In this thesis, a method by which high mineral content Si-CaP/PCL biocomposites with interpenetrating matrices of mineral and polymer phases may be prepared will be demonstrated, in addition to the effects of the various preparation parameters on the biocomposite density, porosity and mechanical properties. This new technique by which dense, primarily ceramic Si-CaP/PCL biocomposites were prepared, allowed for the incorporation of mineral contents ranging between 45-97vol%. Polymer infiltration, accomplished solely by passive capillary uptake over several days, was found to be capable of fully infiltrating the microporosity

  16. Recombination homeostasis of meiosis during spermatogenesis under nicotine treatment

    Directory of Open Access Journals (Sweden)

    Zhai Jingli

    2018-01-01

    Full Text Available Cigarette smoking can affect male fertility via the quality of semen. To explore the effects of nicotine, a major component of cigarettes, on meiotic recombination during spermatogenesis, C57BL/6J male mice were injected with nicotine at a dosage of 0.2 mg/100 g body weight daily for 35 days (nicotine-treated group; mice in the control group were injected with isopycnic normal saline. According to previous expression profiles of mouse sperm, a subset of meiosis-related genes was pooled using bioinformatic analysis. Protein expression was compared between the two groups using by Western blotting and immunohistochemistry. Recombination frequency during the meiosis phase of spermatogenesis was estimated by combined use of chromosome spread and immunofluorescence staining in mouse testes. Data mining analysis indicated that 4 genes that express meiotic topoisomerase-like protein SPO11, MutS protein homolog 4 (MSH4, strand exchange protein RAD51 and MutL protein homologue 1 (MLH1, were associated with the meiosis recombination process. The results of Western blotting and immunohistochemistry further showed that the protein expression of SPO11 (0.73-fold and MSH4 (0.73-fold was downregulated in murine testes after nicotine treatment, whereas the protein expression of both RAD51 (2.06-fold and MLH1 (1.40-fold was upregulated. Unexpectedly, we did not detect a significant difference in recombination frequency in meiosis during spermatogenesis in the nicotine-treated group as compared to the control. Taken together, these results indicate that nicotine can affect the expression profile of restructuring-related genes, but it does not significantly change the recombination frequency during male meiosis. These findings suggest there is a self-regulating mechanism during meiotic chromosome restructuring in male mice that responds to environmental stress.

  17. [Spectroscopic studies on the interaction of nicotine and BSA].

    Science.gov (United States)

    Chen, Yun; Kong, Xiang-rong; Shen, Xinag-can; Liang, Hong

    2005-10-01

    The interaction of nicotine and bovine serum albumin(BSA) was investigated by fluorescence spectra and UV-vis spectra. The fluorescence spectrum showed that BSA fluorescence quench regularly with the addition of nicotine.The fluorescence quenching mechanisms were also studied in pH 5.0, pH 7.4 and pH 11.0 by Stern-Volmer equation, indicating dynamic quenching(pH 5.0) and static quenching(pH 7.4 and pH 11.0) respectively. Association constants (k) of nicotine and BSA at pH 7.4 and pH 11.0 at the temperatures of 20 and 37 degrees C were given by the Lineweaver-Buck equation, which are: k(20 degrees C) = 140.15 L x mol(-1) and k(37 degrees C) = 131.83 mol x L(-1) (pH 7.4), and k(20 degrees C) = 141.76 mol x L(-1), k(37 degrees C) = 27.79 mol x L(-1) (pH 11.0), suggesting that the association constant is effected by the temperature much more remarkably at pH 7.4 than that at pH 11.0 because of the different states of nicotine at different pHs. The UV-Vis spectra exhibit that the absorbance of BSA(210 nm) shifts to red and decreases gradually with the addition of nicotine, reflecting the transition of secondary structure of BSA, namely, the helix of BSA becomes looser. The UV-Vis second derivative spectra and synchronous spectra (delta wavelength = wavelength(em) - wavelength(ex) = 15 nm and delta wavelength = wavelength(em) - wavelength(ex) = 60 nm) imply the change of the microcircumstance of aromatic amino residues of BSA(Trp, Tyr and Phe) from hydrophobicity to hydrophilicity at high concentration of nicotine.

  18. Nicotine as a discriminative stimulus for ethanol use.

    Science.gov (United States)

    Ginsburg, Brett C; Levy, Simon A; Lamb, R J

    2018-01-01

    Abused drugs reinforce behavior; i.e., they increase the probability of the behavior preceding their administration. Abused drugs can also act as discriminative stimuli; i.e., they can set the occasion for responding reinforced by another event. Thus, one abused drug could come to set the occasion for the use of another and this functional relationship may play a role in polysubstance abuse, where common patterns of use could result in this relationship. Here we establish nicotine (0.4mg/kg, ip 5-min pre-session) as a discriminative stimulus for behavior reinforced by ethanol (0.1ml 8% w/v po, versus food) and determine the ability of nicotine (0.02-0.4mg/kg), varenicline (0.1-3.0mg/kg), and ethanol (250 and 500mg/kg) to control responding for ethanol. We compare these results to those from rats where nicotine signaled food was available (and ethanol was not). Nicotine came to function as a discriminative stimulus. Nicotine and varenicline produced dose-dependent increases in responding on the nicotine-appropriate lever while ethanol produced responding on the vehicle-appropriate lever. Whether this responding occurred on the lever that produced ethanol or food access depended on the training condition. These results demonstrate that a drug can come to set the occasion for use of another and suggest that this behavioral mechanism could play an important role in the maintenance of and recovery from polysubstance abuse, depending on the pattern of use. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Complex osteoclastogenic inductive effects of nicotine over hydroxyapatite.

    Science.gov (United States)

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

    2018-02-01

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

  20. Unpacking smokers' beliefs about addiction and nicotine: A qualitative study.

    Science.gov (United States)

    Johnson, Sarah E; Coleman, Blair; Tessman, Greta K; Dickinson, Denise M

    2017-11-01

    Evidence suggests that consumers correctly identify nicotine as addictive; however, many may also harbor misconceptions about its harmfulness. The majority of this evidence is based on survey data, however, which may be prone to some limitations. In the current study, we employed qualitative methods to examine, in their own words, smokers' beliefs about nicotine and addiction. Twelve 1-hr focus groups were conducted in 3 cities in the United States (Columbus, OH; New Orleans, LA; and Washington, DC) from October to November, 2014. Adult cigarette smokers (N = 108), defined as those who reported smoking cigarettes on every day or some days, were segmented by age group (18-25 years and ≥26 years) and tobacco-use behavior. Thematic, in-depth analysis of focus-group discussion transcripts was conducted. Participant demographic information was recorded. Results showed that smokers identify nicotine as a cause of addiction to cigarettes; however, they also attribute their addiction to other factors. When asked about nicotine's effects on the body, immediate physiological effects of smoking (e.g., stimulation, relaxation) were top of mind. Opinions varied in terms of whether nicotine itself was harmful or harmless; many were unsure and/or had not considered this question. Discussions revealed heterogeneity in smokers' beliefs as well as recognition of their own uncertainty and lack of knowledge. The current findings provide insight that smokers may not be as misinformed regarding the relative harms of nicotine and tobacco, as has been suggested by quantitative evidence. Implications for future research are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Efficient transfection of DNA into primarily cultured rat sertoli cells by electroporation.

    Science.gov (United States)

    Li, Fuping; Yamaguchi, Kohei; Okada, Keisuke; Matsushita, Kei; Enatsu, Noritoshi; Chiba, Koji; Yue, Huanxun; Fujisawa, Masato

    2013-03-01

    The expression of exogenous DNA in Sertoli cells is essential for studying its functional genomics, pathway analysis, and medical applications. Electroporation is a valuable tool for nucleic acid delivery, even in primarily cultured cells, which are considered difficult to transfect. In this study, we developed an optimized protocol for electroporation-based transfection of Sertoli cells and compared its efficiency with conventional lipofection. Sertoli cells were transfected with pCMV-GFP plasmid by square-wave electroporation under different conditions. After transfection of plasmid into Sertoli cells, enhanced green fluorescent protein (EGFP) expression could be easily detected by fluorescent microscopy, and cell survival was evaluated by dye exclusion assay using Trypan blue. In terms of both cell survival and the percentage expressing EGFP, 250 V was determined to produce the greatest number of transiently transfected cells. Keeping the voltage constant (250 V), relatively high cell survival (76.5% ± 3.4%) and transfection efficiency (30.6% ± 5.6%) were observed with a pulse length of 20 μm. The number of pulses significantly affected cell survival and EGFP expression (P transfection methods, the transfection efficiency of electroporation (21.5% ± 5.7%) was significantly higher than those of Lipofectamine 2000 (2.9% ± 1.0%) and Effectene (1.9% ± 0.8%) in this experiment (P transfection of Sertoli cells.

  2. Perceptions of Mindfulness in a Low-income, Primarily African American Treatment-Seeking Sample.

    Science.gov (United States)

    Spears, Claire Adams; Houchins, Sean C; Bamatter, Wendy P; Barrueco, Sandra; Hoover, Diana Stewart; Perskaudas, Rokas

    2017-12-01

    Individuals with low socioeconomic status (SES) and members of racial/ethnic minority groups often experience profound disparities in mental health and physical well-being. Mindfulness-based interventions show promise for improving mood and health behaviors in higher-SES and non-Latino White populations. However, research is needed to explore what types of adaptations, if any, are needed to best support underserved populations. This study used qualitative methods to gain information about a) perceptions of mindfulness, b) experiences with meditation, c) barriers to practicing mindfulness, and d) recommendations for tailoring mindfulness-based interventions in a low-income, primarily African American treatment-seeking sample. Eight focus groups were conducted with 32 adults (16 men and 16 women) currently receiving services at a community mental health center. Most participants (91%) were African American. Focus group data were transcribed and analyzed using NVivo 10. A team of coders reviewed the transcripts to identify salient themes. Relevant themes included beliefs that mindfulness practice might improve mental health (e.g., managing stress and anger more effectively) and physical health (e.g., improving sleep and chronic pain, promoting healthier behaviors). Participants also discussed ways in which mindfulness might be consistent with, and even enhance, their religious and spiritual practices. Results could be helpful in tailoring mindfulness-based treatments to optimize feasibility and effectiveness for low-SES adults receiving mental health services.

  3. Identification of a novel CoA synthase isoform, which is primarily expressed in Brain

    International Nuclear Information System (INIS)

    Nemazanyy, Ivan; Panasyuk, Ganna; Breus, Oksana; Zhyvoloup, Alexander; Filonenko, Valeriy; Gout, Ivan T.

    2006-01-01

    CoA and its derivatives Acetyl-CoA and Acyl-CoA are important players in cellular metabolism and signal transduction. CoA synthase is a bifunctional enzyme which mediates the final stages of CoA biosynthesis. In previous studies, we have reported molecular cloning, biochemical characterization, and subcellular localization of CoA synthase (CoASy). Here, we describe the existence of a novel CoA synthase isoform, which is the product of alternative splicing and possesses a 29aa extension at the N-terminus. We termed it CoASy β and originally identified CoA synthase, CoASy α. The transcript specific for CoASy β was identified by electronic screening and by RT-PCR analysis of various rat tissues. The existence of this novel isoform was further confirmed by immunoblot analysis with antibodies directed to the N-terminal peptide of CoASy β. In contrast to CoASy α, which shows ubiquitous expression, CoASy β is primarily expressed in Brain. Using confocal microscopy, we demonstrated that both isoforms are localized on mitochondria. The N-terminal extension does not affect the activity of CoA synthase, but possesses a proline-rich sequence which can bring the enzyme into complexes with signalling proteins containing SH3 or WW domains. The role of this novel isoform in CoA biosynthesis, especially in Brain, requires further elucidation

  4. GOLD HULL AND INTERNODE2 encodes a primarily multifunctional cinnamyl-alcohol dehydrogenase in rice.

    Science.gov (United States)

    Zhang, Kewei; Qian, Qian; Huang, Zejun; Wang, Yiqin; Li, Ming; Hong, Lilan; Zeng, Dali; Gu, Minghong; Chu, Chengcai; Cheng, Zhukuan

    2006-03-01

    Lignin content and composition are two important agronomic traits for the utilization of agricultural residues. Rice (Oryza sativa) gold hull and internode phenotype is a classical morphological marker trait that has long been applied to breeding and genetics study. In this study, we have cloned the GOLD HULL AND INTERNODE2 (GH2) gene in rice using a map-based cloning approach. The result shows that the gh2 mutant is a lignin-deficient mutant, and GH2 encodes a cinnamyl-alcohol dehydrogenase (CAD). Consistent with this finding, extracts from roots, internodes, hulls, and panicles of the gh2 plants exhibited drastically reduced CAD activity and undetectable sinapyl alcohol dehydrogenase activity. When expressed in Escherichia coli, purified recombinant GH2 was found to exhibit strong catalytic ability toward coniferaldehyde and sinapaldehyde, while the mutant protein gh2 completely lost the corresponding CAD and sinapyl alcohol dehydrogenase activities. Further phenotypic analysis of the gh2 mutant plants revealed that the p-hydroxyphenyl, guaiacyl, and sinapyl monomers were reduced in almost the same ratio compared to the wild type. Our results suggest GH2 acts as a primarily multifunctional CAD to synthesize coniferyl and sinapyl alcohol precursors in rice lignin biosynthesis.

  5. GOLD HULL AND INTERNODE2 Encodes a Primarily Multifunctional Cinnamyl-Alcohol Dehydrogenase in Rice1

    Science.gov (United States)

    Zhang, Kewei; Qian, Qian; Huang, Zejun; Wang, Yiqin; Li, Ming; Hong, Lilan; Zeng, Dali; Gu, Minghong; Chu, Chengcai; Cheng, Zhukuan

    2006-01-01

    Lignin content and composition are two important agronomic traits for the utilization of agricultural residues. Rice (Oryza sativa) gold hull and internode phenotype is a classical morphological marker trait that has long been applied to breeding and genetics study. In this study, we have cloned the GOLD HULL AND INTERNODE2 (GH2) gene in rice using a map-based cloning approach. The result shows that the gh2 mutant is a lignin-deficient mutant, and GH2 encodes a cinnamyl-alcohol dehydrogenase (CAD). Consistent with this finding, extracts from roots, internodes, hulls, and panicles of the gh2 plants exhibited drastically reduced CAD activity and undetectable sinapyl alcohol dehydrogenase activity. When expressed in Escherichia coli, purified recombinant GH2 was found to exhibit strong catalytic ability toward coniferaldehyde and sinapaldehyde, while the mutant protein gh2 completely lost the corresponding CAD and sinapyl alcohol dehydrogenase activities. Further phenotypic analysis of the gh2 mutant plants revealed that the p-hydroxyphenyl, guaiacyl, and sinapyl monomers were reduced in almost the same ratio compared to the wild type. Our results suggest GH2 acts as a primarily multifunctional CAD to synthesize coniferyl and sinapyl alcohol precursors in rice lignin biosynthesis. PMID:16443696

  6. Synthesis and nicotinic receptor activity of a hydroxylated tropane

    DEFF Research Database (Denmark)

    Bremner, John B; Godfrey, Colette A; Jensen, Anders A.

    2004-01-01

    (+/-)-3alpha-hydroxy homoepibatidine 4 has been synthesized from the alkaloid scopolamine 5 and its properties as a nicotinic agonist assessed. While still binding strongly, the compound showed reduced agonist potency for the alpha(4)beta(2) nAChR compared with the parent compound epibatidine 1....... Compound 4 also displayed generally similar binding and selectivity profiles at alpha(4)beta(2), alpha(2)beta(4), alpha(3)beta(4), and alpha(4)beta(4) nAChR subtypes to those for nicotine....

  7. Concise synthesis of new bridged-nicotine analogues

    DEFF Research Database (Denmark)

    Crestey, François; Hooyberghs, Geert; Kristensen, Jesper Langgaard

    2012-01-01

    This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively.......This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively....

  8. Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Parimal Chowdhury; Kodetthoor B Udupa

    2006-01-01

    Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine,a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems.In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.

  9. 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

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

    Science.gov (United States)

    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

  11. 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...

  12. Blockade of central nicotine acetylcholine receptor signaling attenuate ghrelin-induced food intake in rodents.

    Science.gov (United States)

    Dickson, S L; Hrabovszky, E; Hansson, C; Jerlhag, E; Alvarez-Crespo, M; Skibicka, K P; Molnar, C S; Liposits, Z; Engel, J A; Egecioglu, E

    2010-12-29

    Here we sought to determine whether ghrelin's central effects on food intake can be interrupted by nicotine acetylcholine receptor (nAChR) blockade. Ghrelin regulates mesolimbic dopamine neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens, partly via cholinergic VTA afferents originating in the laterodorsal tegmental area (LDTg). Given that these cholinergic projections to the VTA have been implicated in natural as well as drug-induced reinforcement, we sought to investigate the role of cholinergic signaling in ghrelin-induced food intake as well as fasting-induced food intake, for which endogenous ghrelin has been implicated. We found that i.p. treatment with the non-selective centrally active nAChR antagonist, mecamylamine decreased fasting-induced food intake in both mice and rats. Moreover, central administration of mecamylamine decreased fasting-induced food intake in rats. I.c.v. ghrelin-induced food intake was suppressed by mecamylamine i.p. but not by hexamethonium i.p., a peripheral nAChR antagonist. Furthermore, mecamylamine i.p. blocked food intake following ghrelin injection into the VTA. Expression of the ghrelin receptor, the growth hormone secretagogue receptor 1A, was found to co-localize with choline acetyltransferase, a marker of cholinergic neurons, in the LDTg. Finally, mecamylamine treatment i.p. decreased the ability of palatable food to condition a place preference. These data suggest that ghrelin-induced food intake is partly mediated via nAChRs and that nicotinic blockade decreases the rewarding properties of food. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Naturally occurring variants of human Α9 nicotinic receptor differentially affect bronchial cell proliferation and transformation.

    Directory of Open Access Journals (Sweden)

    Anna Chikova

    Full Text Available Isolation of polyadenilated mRNA from human immortalized bronchial epithelial cell line BEP2D revealed the presence of multiple isoforms of RNA coded by the CHRNA9 gene for α9 nicotinic acetylcholine receptor (nAChR. BEP2D cells were homozygous for the rs10009228 polymorphism encoding for N442S amino acid substitution, and also contained mRNA coding for several truncated isoforms of α9 protein. To elucidate the biologic significance of the naturally occurring variants of α9 nAChR, we compared the biologic effects of overexpression of full-length α9 N442 and S442 proteins, and the truncated α9 variant occurring due to a loss of the exon 4 sequence that causes frame shift and early termination of the translation. These as well as control vector were overexpressed in the BEP2D cells that were used in the assays of proliferation rate, spontaneous vs. tobacco nitrosamine 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced cellular transformation, and tumorigenicity in cell culture and mice. Overexpression of the S442 variant significantly increased cellular proliferation, and spontaneous and NNK-induced transformation. The N442 variant significantly decreased cellular transformation, without affecting proliferation rate. Overexpression of the truncated α9 significantly decreased proliferation and suppressed cellular transformation. These results suggested that α9 nAChR plays important roles in regulation of bronchial cell growth by endogenous acetylcholine and exogenous nicotine, and susceptibility to NNK-induced carcinogenic transformation. The biologic activities of α9 nAChR may be regulated at the splicing level, and genetic polymorphisms in CHRNA9 affecting protein levels, amino acid sequence and RNA splicing may influence the risk for lung cancer.

  14. Chronic nicotine modifies skeletal muscle Na,K-ATPase activity through its interaction with the nicotinic acetylcholine receptor and phospholemman.

    Directory of Open Access Journals (Sweden)

    Alexander V Chibalin

    Full Text Available Our previous finding that the muscle nicotinic acetylcholine receptor (nAChR and the Na,K-ATPase interact as a regulatory complex to modulate Na,K-ATPase activity suggested that chronic, circulating nicotine may alter this interaction, with long-term changes in the membrane potential. To test this hypothesis, we chronically exposed rats to nicotine delivered orally for 21-31 days. Chronic nicotine produced a steady membrane depolarization of ∼3 mV in the diaphragm muscle, which resulted from a net change in electrogenic transport by the Na,K-ATPase α2 and α1 isoforms. Electrogenic transport by the α2 isoform increased (+1.8 mV while the activity of the α1 isoform decreased (-4.4 mV. Protein expression of Na,K-ATPase α1 or α2 isoforms and the nAChR did not change; however, the content of α2 subunit in the plasma membrane decreased by 25%, indicating that its stimulated electrogenic transport is due to an increase in specific activity. The physical association between the nAChR, the Na,K-ATPase α1 or α2 subunits, and the regulatory subunit of the Na,K-ATPase, phospholemman (PLM, measured by co-immuno precipitation, was stable and unchanged. Chronic nicotine treatment activated PKCα/β2 and PKCδ and was accompanied by parallel increases in PLM phosphorylation at Ser(63 and Ser(68. Collectively, these results demonstrate that nicotine at chronic doses, acting through the nAChR-Na,K-ATPase complex, is able to modulate Na,K-ATPase activity in an isoform-specific manner and that the regulatory range includes both stimulation and inhibition of enzyme activity. Cholinergic modulation of Na,K-ATPase activity is achieved, in part, through activation of PKC and phosphorylation of PLM.

  15. 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.

  16. Effects of nicotine on body weight in rats with access to "junk" foods.

    Science.gov (United States)

    Grunberg, N E; Popp, K A; Winders, S E

    1988-01-01

    The present experiment examined effects of nicotine on body weight of male and female rats when Oreo cookies, potato chips, laboratory chow, and water were available. Body weight and eating behavior were measured for 17-day periods before, during, and after nicotine or saline administration. There was an inverse relationship between nicotine and body weight. These effects were paralleled by changes in consumption of sweet foods. There were no effects of nicotine on salty or bland food consumption. Excessive gains in body weight after cessation of nicotine administration were greater for females than for males.

  17. Pressure suppression device

    International Nuclear Information System (INIS)

    Mizumachi, Wataru; Fukuda, Akira; Kitaguchi, Hidemi; Shimizu, Toshiaki.

    1976-01-01

    Object: To relieve and absorb impact wave vibrations caused by steam and non-condensed gases releasing into the pressure suppression chamber at the time of an accident. Structure: The reactor container is filled with inert gases. A safety valve attached main steam pipe is provided to permit the excessive steam to escape, the valve being communicated with the pressure suppression chamber through an exhaust pipe. In the pressure suppression chamber, a doughnut-like cylindrical outer wall is filled at its bottom with pool water to condense the high temperature vapor released through the exhaust pipe. A head portion of a vent tube which leads the exhaust pipe is positioned at the top, and a down comer and an exhaust vent tube are locked by means of steady rests. At the bottom is mounted a pressure adsorber device which adsorbs a pressure from the pool water. (Kamimura, M.)

  18. Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability.

    Science.gov (United States)

    Stiles, Mitchell F; Campbell, Leanne R; Graff, Donald W; Jones, Bobbette A; Fant, Reginald V; Henningfield, Jack E

    2017-09-01

    Electronic cigarettes (ECs) are becoming popular alternatives for smokers, but there has been limited study of their abuse liability. The objective of this study was to evaluate the abuse liability of three Vuse Solo ECs, ranging from 14 to 36 mg in nicotine content, relative to high- and low-abuse liability comparator products (usual brand combustible cigarettes and nicotine gum, respectively) in a group of 45 EC-naïve smokers. Enrolled subjects' ratings of subjective effects and nicotine uptake over 6 h were used to measure abuse liability and pharmacokinetics following in-clinic use of each EC. Use of Vuse Solo resulted in subjective measures and nicotine uptake that were between those of combustible cigarettes and nicotine gum, although generally closer to nicotine gum. Compared to combustible cigarettes, use of Vuse Solo resulted in significantly lower scores in measures of product liking, positive effects, and intent to use again. These pharmacodynamic findings were consistent with the pharmacokinetic data, showing that cigarettes produced substantially faster and higher levels of nicotine uptake as compared to Vuse Solo and nicotine gum. Vuse Solo resulted in more rapid initial uptake of nicotine compared to nicotine gum, but peak concentration and long-term extent of uptake were not different or were lower with Vuse. Collectively, these findings suggest that Vuse Solo likely has an abuse liability that is somewhat greater than nicotine gum but lower than cigarettes. ClinicalTrials.gov identifier: NCT02269514.

  19. Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish

    International Nuclear Information System (INIS)

    Welsh, Lillian; Tanguay, Robert L.; Svoboda, Kurt R.

    2009-01-01

    Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K.R., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731-10741). In that study, we did not consider the potential role that altered skeletal muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.

  20. Combinatorial effect of nicotine and black tea on heart rate variability: Useful or harmful?

    Science.gov (United States)

    Joukar, S; Sheibani, M

    2017-06-01

    The effect of nicotine on heart rate variability (HRV) is controversial. Autonomic nervous system is the main regulator of heart rhythm, and heart rate variability is an appropriate index to assessment of the effects of the autonomic system on heart. In this study, the combination effect of nicotine and black tea consumption on sympatho-vagal balance and heart rate variability was investigated in rats. Male Wistar rats were randomized into four groups as control, tea (2.5 g/100 cc, daily), nicotine (2 mg/kg/d) and tea plus nicotine groups which treated for 28 days, and in the 29th day, their electrocardiograms (lead II) were recorded. The mean of high-frequency power (HF) in tea, nicotine and tea plus nicotine groups was significantly more than control group (P nicotine and tea + nicotine groups was significantly less than control group (P nicotine and tea + nicotine groups in comparison with control group (P nicotine or their combination with dosages used in this study can increase the heart rate variability and improve the sympatho-vagal balance in rat. © 2017 John Wiley & Sons Ltd.

  1. Neuroscience of nicotine for addiction medicine: novel targets for smoking cessation medications.

    Science.gov (United States)

    D'Souza, Manoranjan S

    2016-01-01

    Morbidity and mortality associated with tobacco smoking constitutes a significant burden on healthcare budgets all over the world. Therefore, promoting smoking cessation is an important goal of health professionals and policy makers throughout the world. Nicotine is a major psychoactive component in tobacco that is largely responsible for the widespread addiction to tobacco. A majority of the currently available FDA-approved smoking cessation medications act via neuronal nicotinic receptors. These medications are effective in approximately half of all the smokers, who want to quit and relapse among abstinent smokers continues to be high. In addition to relapse among abstinent smokers, unpleasant effects associated with nicotine withdrawal are a major motivational factor in continued tobacco smoking. Over the last two decades, animal studies have helped in identifying several neural substrates that are involved in nicotine-dependent behaviors including those associated with nicotine withdrawal and relapse to tobacco smoking. In this review, first the role of specific brain regions/circuits that are involved in nicotine dependence will be discussed. Next, the review will describe the role of specific nicotinic receptor subunits in nicotine dependence. Finally, the review will discuss the role of classical neurotransmitters (dopamine, serotonin, noradrenaline, glutamate, and γ-aminobutyric acid) as well as endogenous opioid and endocannabinoid signaling in nicotine dependence. The nicotinic and nonnicotinic neural substrates involved in nicotine-dependent behaviors can serve as possible targets for future smoking cessation medications. © 2016 Elsevier B.V. All rights reserved.

  2. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    Science.gov (United States)

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  3. Unpredictability of nectar nicotine promotes outcrossing by hummingbirds in Nicotiana attenuata.

    Science.gov (United States)

    Kessler, Danny; Bhattacharya, Samik; Diezel, Celia; Rothe, Eva; Gase, Klaus; Schöttner, Matthias; Baldwin, Ian T

    2012-08-01

    Many plants use sophisticated strategies to maximize their reproductive success via outcrossing. Nicotiana attenuata flowers produce nectar with nicotine at concentrations that are repellent to hummingbirds, increasing the number of flowers visited per plant. In choice tests using native hummingbirds, we show that these important pollinators learn to tolerate high-nicotine nectar but prefer low-nicotine nectar, and show no signs of nicotine addiction. Nectar nicotine concentrations, unlike those of other vegetative tissues, are unpredictably variable among flowers, not only among populations, but also within populations, and even among flowers within an inflorescence. To evaluate whether variations in nectar nicotine concentrations increase outcrossing, polymorphic microsatellite markers, optimized to evaluate paternity in native N. attenuata populations, were used to compare outcrossing in plants silenced for expression of a biosynthetic gene for nicotine production (Napmt1/2) and in control empty vector plants, which were antherectomized and transplanted into native populations. When only exposed to hummingbird pollinators, seeds produced by flowers with nicotine in their nectar had a greater number of genetically different sires, compared to seeds from nicotine-free flowers. As the variation in nectar nicotine levels among flowers in an inflorescence decreased in N. attenuata plants silenced in various combinations of three Dicer-like (DCL) proteins, small RNAs are probably involved in the unpredictable variation in nectar nicotine levels within a plant. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  4. Thyroxin hormone suppression treatment

    International Nuclear Information System (INIS)

    Samuel, A.M.

    1999-01-01

    One of the important modalities of treatment of thyroid cancer (TC) after surgery is the administration of thyroxin as an adjuvant treatment. The analysis supports the theory that thyroid suppression plays an important role in patient management. 300 μg of thyroxin, as this is an adequate dose for suppression is given. Ideally the dose should be tailored by testing s-TSH levels. However, since a large number of the patients come from out station cities and villages this is impractical. We therefore depend on clinical criteria of hyperthyroid symptoms and adjust the dose. Very few patients need such adjustment

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

    Science.gov (United States)

    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.

  6. 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.

  7. 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.

  8. The effect of nicotine pre-exposure on demand for cocaine and sucrose in male rats.

    Science.gov (United States)

    Schwartz, Lindsay P; Kearns, David N; Silberberg, Alan

    2018-06-01

    The aim of the present study was to determine how nicotine pre-exposure affects the elasticity of demand for intravenous cocaine and for sucrose pellets in adult male rats. In Experiment 1, demand for cocaine was assessed in rats that had nicotine in their drinking water. Nicotine pre-exposure significantly decreased rats' willingness to defend cocaine consumption as the price (measured as the number of responses per cocaine infusion) increased compared with a control group with no nicotine pre-exposure. That is, nicotine increased the elasticity of demand for cocaine infusions. Experiment 2 repeated the first experiment, but with rats working for sucrose pellets instead of cocaine. Nicotine pre-exposure had no effect on the elasticity of demand for sucrose. This pattern of results suggests that nicotine pre-exposure can reduce the reinforcing effects of cocaine, but not sucrose, in adult male rats.

  9. A model for evolution and regulation of nicotine biosynthesis regulon in tobacco.

    Science.gov (United States)

    Kajikawa, Masataka; Sierro, Nicolas; Hashimoto, Takashi; Shoji, Tsubasa

    2017-06-03

    In tobacco, the defense alkaloid nicotine is produced in roots and accumulates mainly in leaves. Signaling mediated by jasmonates (JAs) induces the formation of nicotine via a series of structural genes that constitute a regulon and are coordinated by JA-responsive transcription factors of the ethylene response factor (ERF) family. Early steps in the pyrrolidine and pyridine biosynthesis pathways likely arose through duplication of the polyamine and nicotinamide adenine dinucleotide (NAD) biosynthetic pathways, respectively, followed by recruitment of duplicated primary metabolic genes into the nicotine biosynthesis regulon. Transcriptional regulation of nicotine biosynthesis by ERF and cooperatively-acting MYC2 transcription factors is implied by the frequency of cognate cis-regulatory elements for these factors in the promoter regions of the downstream structural genes. Indeed, a mutant tobacco with low nicotine content was found to have a large chromosomal deletion in a cluster of closely related ERF genes at the nicotine-controlling NICOTINE2 (NIC2) locus.

  10. 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

  11. Belief about nicotine Modulates subjective craving and insula activity in Deprived smokers

    DEFF Research Database (Denmark)

    Gu, X. S.; Lohrenz, Terry; Salas, Ramiro

    2016-01-01

    Little is known about the specific neural mechanisms through which cognitive factors influence craving and associated brain responses, despite the initial success of cognitive therapies in treating drug addiction. In this study, we investigated how cognitive factors such as beliefs influence...... subjective craving and neural activities in nicotine-addicted individuals using model-based functional magnetic resonance imaging (fMRI) and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced placebo design, which crossed beliefs about nicotine (told "nicotine" vs. told "no......, smokers demonstrated significantly reduced craving after smoking when told "nicotine in cigarette" but showed no change in craving when told "no nicotine." Second, neural activity in the insular cortex related to craving was only significant when smokers were told "nicotine" but not when told "no nicotine...

  12. Homogenous stretching or detachment faulting? Which process is primarily extending the Aegean crust

    Science.gov (United States)

    Kumerics, C.; Ring, U.

    2003-04-01

    In extending orogens like the Aegean Sea of Greece and the Basin-and-Range province of the western United States, knowledge of rates of tectonic processes are important for understanding which process is primarily extending the crust. Platt et al. (1998) proposed that homogeneous stretching of the lithosphere (i.e. vertical ductile thinning associated with a subhorizontal foliation) at rates of 4-5 km Myr-1 is the dominant process that formed the Alboran Sea in the western Mediterranean. The Aegean Sea in the eastern Mediterranean is well-known for its low-angle normal faults (detachments) (Lister et al., 1984; Lister &Forster, 1996) suggesting that detachment faulting may have been the primary agent achieving ~>250 km (McKenzie, 1978) of extension since the Miocene. Ring et al. (2003) provided evidence for a very fast-slipping detachment on the islands of Syros and Tinos in the western Cyclades, which suggests that normal faulting was the dominant tectonic process that formed the Aegean Sea. However, most extensional detachments in the Aegean do not allow to quantify the amount of vertical ductile thinning associated with extension and therefore a full evaluation of the significance of vertical ductile thinning is not possible. On the Island of Ikaria in the eastern Aegean Sea, a subhorizontal extensional ductile shear zone is well exposed. We studied this shear zone in detail to quantify the amount of vertical ductile thinning associated with extension. Numerous studies have shown that natural shear zones usually deviate significantly from progressive simple shear and are characterized by pronounced shortening perpendicular to the shear zone. Numerous deformed pegmatitic veins in this shear zone on Ikaria allow the reconstruction of deformation and flow parameters (Passchier, 1990), which are necessary for quantifying the amount of vertical ductile thinning in the shear zone. Furthermore, a flow-path and finite-strain study in a syn-tectonic granite, which

  13. A common biological basis of obesity and nicotine addiction

    NARCIS (Netherlands)

    T.E. Thorgeirsson (Thorgeir); D.F. Gudbjartsson (Daniel); P. Sulem (Patrick); S. Besenbacher (Søren); U. Styrkarsdottir (Unnur); G. Thorleifsson (Gudmar); G.B. Walters (Bragi); H. Furberg (Helena); P. Sullivan (Patrick); J. Marchini (Jonathan); M.I. McCarthy (M.); V. Steinthorsdottir (Valgerdur); U. Thorsteinsdottir (Unnur); J-A. Zwart (John-Anker); I. Surakka (Ida); J.M. Vink (Jacqueline); N. Amin (Najaf); F. Geller (Frank); T. Rafnar (Thorunn); T. Esko (Tõnu); S. Walter (Stefan); C. Gieger (Christian); R. Rawal (R.); M. Mangino (Massimo); I. Prokopenko (Inga); R. Mägi (Reedik); K. Keskitalo (Kaisu); I.H. Gudjonsdottir (Iris); S. Gretarsdottir (Solveig); H. Stefansson (Hreinn); Y.S. Aulchenko (Yurii); M. Nelis (Mari); K.K.H. Aben (Katja); M. den Heijer (Martin); N. Soranzo (Nicole); A.M. Valdes (Ana Maria); C.J. Steves (Claire); A.G. Uitterlinden (André); A. Hofman (Albert); A. Tönjes (Anke); P. Kovacs (Peter); J.J. Hottenga (Jouke Jan); G.A.H.M. Willemsen (Gonneke); N. Vogelzangs (Nicole); A. Döring (Angela); N. Dahmen (N.); B. Nitz (Barbara); S. Ripatti (Samuli); M. Perola (Markus); J. Kettunen (Johannes); A.L. Hartikainen; A. Pouta (Anneli); J. Laitinen (Jaana); M.K. Isohanni (Matti); S. Huei-Yi (Shen); M. Allen (Maxine); M. Krestyaninova (Maria); A. Hall (Anne); J.R. Thompson (John); H. Oskarsson (Hogni); T. Tyrfingsson (Thorarinn); L.A.L.M. Kiemeney (Bart); M.-R. Jarvelin (Marjo-Riitta); V. Salomaa (Veikko); M. Stumvoll (Michael); T.D. Spector (Timothy); H.E. Wichmann (Heinz Erich); A. Metspalu (Andres); N.J. Samani (Nilesh); B.W.J.H. Penninx (Brenda); B.A. Oostra (Ben); D.I. Boomsma (Dorret); H.W. Tiemeier (Henning); C.M. van Duijn (Cornelia); J. Kaprio (Jaakko); J.R. Gulcher (Jeffrey); Y. Kim (Yunjung); J. Dackor (Jennifer); E.A. Boerwinkle (Eric); N. Franceschini (Nora); D. Ardissino (Diego); L. Bernardinelli (Luisa); P.M. Mannucci (Pier); F. Mauri (Francesco); P.A. Merlini (Piera); D. Absher (Devin); T.L. Assimes (Themistocles); S.P. Fortmann (Stephen); C. Iribarren (Carlos); J.W. Knowles (Joshua); T. Quertermous (Thomas); L. Ferrucci (Luigi); T. Tanaka (Toshiko); J.C. Bis (Joshua); H. Furberg (Helena); T. Haritunians (Talin); B. McKnight (Barbara); B.M. Psaty (Bruce); K.D. Taylor (Kent); E.L. Thacker (Evan); P. Almgren (Peter); L. Groop (Leif); C. Ladenvall (Claes); M. Boehnke (Michael); A.U. Jackson (Anne); K.L. Mohlke (Karen); H.M. Stringham (Heather); J. Tuomilehto (Jaakko); E.J. Benjamin (Emelia); S.J. Hwang; D. Levy (Daniel); S.R. Preis; R.S. Vasan (Ramachandran Srini); J. Duan (Jubao); P.V. Gejman (Pablo); D.F. Levinson (Douglas); A.R. Sanders (Alan); J. Shi (Jianxin); E.H. Lips (Esther); J.D. McKay (James); A. Agudo (Antonio); L. Barzan (Luigi); V. Bencko (Vladimir); S. Benhamou (Simone); X. Castellsagué (Xavier); C. Canova (Cristina); D.I. Conway (David); E. Fabianova (Eleonora); L. Foretova (Lenka); V. Janout (Vladimir); C.M. Healy (Claire); I. Holcátová (Ivana); K. Kjaerheim (Kristina); P. Lagiou; J. Lissowska (Jolanta); R. Lowry (Ray); T.V. MacFarlane (Tatiana); D. Mates (Dana); L. Richiardi (Lorenzo); P. Rudnai (Peter); N. Szeszenia-Dabrowska (Neonilia); D. Zaridze; A. Znaor (Ariana); M. Lathrop (Mark); P. Brennan (Paul); S. Bandinelli (Stefania); T.M. Frayling (Timothy); J.M. Guralnik (Jack); Y. Milaneschi (Yuri); J.R.B. Perry (John); D. Altshuler (David); R. Elosua (Roberto); S. Kathiresan (Sekar); G. Lucas (Gavin); O. Melander (Olle); C.J. O'Donnell (Christopher); S.M. Schwartz (Stephen); B.F. Voight (Benjamin); G.D. Smith; E.J.C. de Geus (Eco); S.J. Chanock (Stephen); F. Gu (Fangyi); S.E. Hankinson (Susan); D. Hunter (David); D.I. Chasman (Daniel); B.M. Everett (Brendan); G. Paré (Guillaume); P.M. Ridker (Paul); M.D. Li (Ming); H.H. Maes (Hermine); J. Audrain-Mcgovern (Janet); D. Posthuma (Danielle); L.M. Thornton (Laura); C. Lerman (Caryn); J.E. Rose (Jed); J.P.A. Ioannidis (John); P. Kraft (Peter); D.Y. Lin (Dan); J. Liu (Jason); P. Muglia (Pierandrea); D. Waterworth (Dawn); A.D. Pillai (Ajay); P. Muglia (Pierandrea); L. Middleton (Lefkos); W. Berrettini (Wade); C.W. Knouff (Christopher); X. Yuan (Xin); G. Waeber (Gérard); P. Vollenweider (Peter); M. Preisig (Martin); N.J. Wareham (Nick); J.H. Zhao (Jing Hua); R.J.F. Loos (Ruth); I.E. Barroso (Inês); K-T. Khaw (Kay-Tee); S.M. Grundy (Scott); P. Barter (Phil); R. Mahley (Robert); Y.A. Kesaniemi (Antero); R. McPherson (Ruth); J. Vincent (John); J.S. Strauss (John S); J. Kennedy (James); A.E. Farmer (Anne E); P. Mcguffin (Peter); R.N. Day (Richard); K. Matthews (Keith); A.B. Bakke (Arnold B.); A. Gulsvik (Amund); S. Lucae (Susanne); M. Ising (Marcus); T. Brueckl (Tanja); S. Horstmann (Sonja); J. Heinrich (Joachim); C. Lamina (Claudia); O. Polasek (Ozren); L. Zgaga (Lina); J.E. Huffman (Jennifer); S. Campbell (Susan); J.S. Kooner (Jaspal); J.C. Chambers (John); M.S. Burnett; J. Devaney (Joseph); A.D. Pichard; K.M. Kent (Kenneth); L.F. Satler; J.M. Lindsay (Joseph); R. Waksman (Ron); S.E. Epstein (Stephen); J.F. Wilson (James); S.H. Wild (Sarah); H. Campbell (Harry); V. Vitart (Veronique); M.P. Reilly (Muredach); M. Li (Mingyao); L. Qu (Liming); A. Wilensky (Asaf); W. Matthai (William); H. Hakonarson (Hakon); D.J. Rader (Daniel); A. Franke (Andre); M. Wittig (Michael); A. Schäfer (Arne); M. Uda (Manuela); A. Terracciano; X. Xiao (Xiangjun); F. Busonero; P. Scheet (Paul); D. Schlessinger; D.S. Clair; D. Rujescu (Dan); G.R. Abecasis (Gonçalo); H.J. Grabe (Hans Jörgen); A. Teumer (Alexander); H. Völzke (Henry); A. Petersmann (Astrid); U. John (Ulrich); I. Rudan (Igor); C. Hayward (Caroline); A.F. Wright (Alan); I. Kolcic (Ivana); B.J. Wright (Benjamin); A.J. Balmforth (Anthony); C. Anderson (Carl); T. Ahmed (Tariq); J. Mathew (Joseph); M. Parkes (Miles); J. Satsangi (Jack); M. Caulfield (Mark); P. Munroe (Patricia); M. Farrall (Martin); A. Dominiczak (Anna); H. Worthington (Helen); W. Thomson (Wendy); D.S. Eyre (Dylan Samuel); A. Barton (Anne); V. Mooser (Vincent); C. Francks (Clyde)

    2013-01-01

    textabstractSmoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system

  14. Assessment of Nicotine Exposure From Active Human Cigarette Smoking Time

    Directory of Open Access Journals (Sweden)

    Cahours Xavier

    2017-09-01

    Full Text Available The burning of a cigarette is a series of consecutive sequences of both passive and active burnings when a smoking cycle is applied to the cigarette. A previous study, using a smoking machine, showed that cigarette nicotine yields are dependent linearly on the difference between the time of smouldering (passive burning and the time of smoking (active burning. It is predicted that the smoker’s nicotine yield increases when the intensity of smoking increases, i.e., when the time to smoke a cigarette (smoking time decreases. Note that observations made on machines might not be comparable to human behaviours. The aim of this study was to determine whether nicotine mouth-level exposure could be predicted through measurement of human smoking time. A smoking behaviour study was conducted to compare human smoking nicotine yields obtained from both filter tip analysis and the cigarette burning time model. Results showed that smokers’ exposure to the smoke depends essentially on the speed at which the cigarette is smoked. An increase in human smoking intensity, resulting in a decrease in smoking time, generates an increase in smoke exposure, whatever the puff number, puff duration, puff volume and filter ventilation (open or blocked. The association of a machine smoking yield with a corresponding smoking time, and the time taken by a consumer to smoke the cigarette would provide information on the exposure to smoke constituents in a simple and effective manner.

  15. Honey Attenuates the Detrimental Effects of Nicotine on Testicular ...

    African Journals Online (AJOL)

    olayemitoyin

    reduction in percentage sperm motility, viability, morphology and counts were observed in nicotine group (p<0.05) compared to control. Serum FSH, LH and ... Honey is a natural product of bees formed from nectar collected from flowering ..... Regulatory Protein Expression in Adult Albino Rats: Possible Influence on Pituitary ...

  16. Mutagenicity of nicotine in Schistosoma mansoni - infected mice ...

    African Journals Online (AJOL)

    Analysis of meiotic chromosomes showed significant elevation in the Schistosoma-infected mice. Administration of nicotine to infected mice substantially increased the percentages of micronucleated cells and total CAs. The percentage of chromosomal abnormalities in spermatocyte metaphase-I cells increased significantly ...

  17. Synthesis and antinociceptive activity of methyl nicotinate | Erharuyi ...

    African Journals Online (AJOL)

    ... neutralization of the reaction mixture with 10% sodium bicarbonate. The product was purified by column chromatography and purity ascertained by thin layer chromatography. Structure of the desired product was confirmed by NMR and Mass spectroscopy. Methyl nicotinate was obtained as a white powder (m.p. 40-42oC, ...

  18. Single molecule transistor based nanopore for the detection of nicotine

    Energy Technology Data Exchange (ETDEWEB)

    Ray, S. J., E-mail: ray.sjr@gmail.com [Institute of Materials Science, Technical University of Darmstadt, Alarich-Weiss-Str. 2, 64287 Darmstadt (Germany)

    2014-12-28

    A nanopore based detection methodology was proposed and investigated for the detection of Nicotine. This technique uses a Single Molecular Transistor working as a nanopore operational in the Coulomb Blockade regime. When the Nicotine molecule is pulled through the nanopore area surrounded by the Source(S), Drain (D), and Gate electrodes, the charge stability diagram can detect the presence of the molecule and is unique for a specific molecular structure. Due to the weak coupling between the different electrodes which is set by the nanopore size, the molecular energy states stay almost unaffected by the electrostatic environment that can be realised from the charge stability diagram. Identification of different orientation and position of the Nicotine molecule within the nanopore area can be made from specific regions of overlap between different charge states on the stability diagram that could be used as an electronic fingerprint for detection. This method could be advantageous and useful to detect the presence of Nicotine in smoke which is usually performed using chemical chromatography techniques.

  19. Passive exposure to nicotine from e-cigarettes.

    Science.gov (United States)

    Gallart-Mateu, D; Elbal, L; Armenta, S; de la Guardia, M

    2016-05-15

    A procedure based on the use of ion mobility spectrometry (IMS), after liquid-liquid microextraction (LLME), has been successfully employed for the determination of passive exposure to nicotine from cigarette and e-cigarette smoking. Nicotine has been determined in exhaled breath and oral fluids of both, active and passive smokers. The aforementioned studies, made in closed environments, evidenced that the exhaled breath after conventional blend cigarette smoke provides nicotine levels of the order of 220 ng per puff, in the case of experienced smokers, being exhaled only 32 ng in the case of e-cigarettes. On the other hand, the nicotine amount in oral fluids of passive vapers was between 8 and 14 µg L(-1) lower than the average value of 38±14 µg L(-1) found for passive smokers of rolling tobacco and clearly lower than the 79±36 µg L(-1) obtained from passive smokers of classical yellow blend. This study was also placed in the frame of the verification of the e-cigarettes composition. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Andreasen T., Jesper; Arvaniti, Maria

    2016-01-01

    Nicotinic acetylcholine receptors (nAChRs) have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimer's disease (AD) due to their positioning within regions of the brain critical in learning and memory, such as the prefrontal cortex and hippocampus...

  1. Single molecule transistor based nanopore for the detection of nicotine

    Science.gov (United States)

    Ray, S. J.

    2014-12-01

    A nanopore based detection methodology was proposed and investigated for the detection of Nicotine. This technique uses a Single Molecular Transistor working as a nanopore operational in the Coulomb Blockade regime. When the Nicotine molecule is pulled through the nanopore area surrounded by the Source(S), Drain (D), and Gate electrodes, the charge stability diagram can detect the presence of the molecule and is unique for a specific molecular structure. Due to the weak coupling between the different electrodes which is set by the nanopore size, the molecular energy states stay almost unaffected by the electrostatic environment that can be realised from the charge stability diagram. Identification of different orientation and position of the Nicotine molecule within the nanopore area can be made from specific regions of overlap between different charge states on the stability diagram that could be used as an electronic fingerprint for detection. This method could be advantageous and useful to detect the presence of Nicotine in smoke which is usually performed using chemical chromatography techniques.

  2. For Nicotine, Dose Matters | Center for Cancer Research

    Science.gov (United States)

    Nicotine replacement therapy (NRT) is frequently part of a person’s regimen for smoking cessation. The U.S. Food and Drug Administration has approved use of this approach for 12 weeks in supervised quitting programs. Unfortunately for some patients, though, this length of time is not long enough to break their addiction to tobacco. 

  3. Nicotine Modulates the Long-Lasting Storage of Fear Memory

    Science.gov (United States)

    Lima, Ramon H.; Radiske, Andressa; Kohler, Cristiano A.; Gonzalez, Maria Carolina; Bevilaqua, Lia R.; Rossato, Janine I.; Medina, Jorge H.; Cammarota, Martin

    2013-01-01

    Late post-training activation of the ventral tegmental area (VTA)-hippocampus dopaminergic loop controls the entry of information into long-term memory (LTM). Nicotinic acetylcholine receptors (nAChR) modulate VTA function, but their involvement in LTM storage is unknown. Using pharmacological and behavioral tools, we found that…

  4. Effects of Oral Administration of Nicotine on Organ Weight, Serum ...

    African Journals Online (AJOL)

    This study investigated the effects of oral administration of nicotine on body and reproductive organ weight, serum testosterone level and testicular histology in adult male rats. Forty male rats divided into five groups and treated for a period of 30 days with 0.5mg/kg (low dose) and 1.0mg/kg (high dose) body weight of ...

  5. Genetics of addictive behavior: the example of nicotine dependence.

    Science.gov (United States)

    Gorwood, Philip; Le Strat, Yann; Ramoz, Nicolas

    2017-09-01

    The majority of addictive disorders have a significant heritability-roughly around 50%. Surprisingly, the most convincing association (a nicotinic acetylcholine receptor CHRNA5-A3-B4 gene cluster in nicotine dependence), with a unique attributable risk of 14%, was detected through a genome-wide association study (GWAS) on lung cancer, although lung cancer has a low heritability. We propose some explanations of this finding, potentially helping to understand how a GWAS strategy can be successful. Many endophenotypes were also assessed as potentially modulating the effect of nicotine, indirectly facilitating the development of nicotine dependence. Challenging the involved phenotype led to the demonstration that other potentially overlapping disorders, such as schizophrenia and Parkinson disease, could also be involved, and further modulated by parent monitoring or the existence of a smoking partner. Such a complex mechanism of action is compatible with a gene-environment interaction, most clearly explained by epigenetic factors, especially as such factors were shown to be, at least partly, genetically driven.

  6. Risk and Protective Factors for Nicotine Dependence in Adolescence

    Science.gov (United States)

    Hu, Mei-Chen; Griesler, Pamela; Schaffran, Christine; Kandel, Denise

    2011-01-01

    Background: We investigated the role of psychosocial and proximal contextual factors on nicotine dependence in adolescence. Methods: Data on a multiethnic cohort of 6th to 10th graders from the Chicago public schools were obtained from four household interviews conducted with adolescents over two years and one interview with mothers. Structural…

  7. Effects of Nicotine Withdrawal in Adult Male and Female Rats

    Science.gov (United States)

    2008-01-01

    the planning and organization strategies required of the experimentalist. I am also indebted to Manuel Marwein, Alberta Nyarko, Becca Dieffenbach, Juan ...no difference in self-administration behavior between women who were randomly assigned to placebo and nicotine (Perkins, Grobe, D’Amico, Fonte

  8. 4 acute nicotine induced pressor response is in part due

    African Journals Online (AJOL)

    DR. AMINU

    increases in heart rate in both normal and in nicotine treated rats but the increases shows no significant differences. ... pre-eclampsia in pregnant women by reduction of production .... (Hilton, 1965) and events occurring in man stress ... during emotional stress in normotensive and ... mechanism contributing to ischemic left.

  9. Nicotinic receptor-associated modulation of stimulatory and inhibitory neurotransmitters in NNK-induced adenocarcinoma of the lungs and pancreas

    Science.gov (United States)

    Al-Wadei, Hussein A. N.; Schuller, Hildegard M.

    2012-01-01

    Small airway-derived pulmonary adenocarcinoma (PAC) and pancreatic ductal adenocarcinoma (PDAC) are among the most common human cancers and smoking is a risk factor for both. Emerging research has identified cAMP signaling stimulated by the stress neurotransmitters adrenaline and noradrenaline as important stimulators of several adenocarcinomas, including PAC and PDAC. The nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent mutagen and the most powerful tobacco carcinogen. NNK is also an agonist for nicotinic acetylcholine receptors (nAChRs). Using hamster models of NNK-induced PAC and PDAC, we have tested the hypothesis that in analogy to chronic effects of nicotine in the brain, NNK may modulate the α7- and α4β2nAChRs, causing an increase in stress neurotransmitters and decrease in the inhibitory neurotransmitter γ-aminobutyric acid (GABA). In support of our hypothesis, immunoassays showed a significant increase in serum adrenaline/noradrenaline and increased intracellular cAMP in the cellular fraction of blood of NNK treated hamsters. Western blots were done with cells harvested by laser capture microcopy from control small airway epithelia, alveolar epithelia, pancreatic islet and pancreatic duct epithelia and from NNK-induced PACs and PDACs. The GABA synthesizing enzyme glutamate decarboxylase 65 (GAD65) and GABA were suppressed in NNK-induced PACs and PDACs whereas protein expression of the α7nAChR, α4nAChR as well as p-CREB and p-ERK1/2 were upregulated. These findings suggest, for the first time, that NNK-induced alterations in regulatory nAChRs may contribute to the development of smoking-associated PAC and PDAC by disturbing the balance between cancer stimulating and inhibiting neurotransmitters. PMID:19274673

  10. Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer.

    Science.gov (United States)

    Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D; Upadhyay, Daya

    2009-02-01

    Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 muM) followed by cisplatin (35 muM) plus etoposide (20 muM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4'diisothiocyanatostilbene-2,2'disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-rho0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer

  11. Pressure suppressing device

    International Nuclear Information System (INIS)

    Naito, Makoto.

    1980-01-01

    Purpose: To prevent the pressure in the reactor container from excessively increasing even when vapor leaks from the dry well to a space of the suppression chamber, without passing though the suppression pool at the time of loss of coolant accident. Constitution: When vapor of a high temperature and a high pressure at the time of loss of coolant accident flows from the dry well to the suppression chamber without passing through suppression pool water, vapor dose not condense with pool water, and therefore the pressure within the chamber abnormally increases. For this reason, this abnormal pressure is detected by a pressure detector thereby to start the operations of a blower and a pump. By starting the blower, the pressure in the dry well becomes lower than the pressure in the chamber, and vapor entirely passes through the pool water and entirely condenses with the pool water. By starting the pump, the pool water is sprayed over the space of the chamber, and vapor in the space is condensed. (Yoshino, Y.)

  12. Multimodal Neuroimaging Differences in Nicotine Abstinent vs. Satiated Smokers.

    Science.gov (United States)

    Chaarani, Bader; Spechler, Philip A; Ivanciu, Alexandra; Snowe, Mitchell; Nickerson, Joshua P; Higgins, Stephen T; Garavan, Hugh

    2018-04-06

    Research on cigarette smokers suggests cognitive and behavioral impairments. However, much remains unclear how the functional neurobiology of smokers is influenced by nicotine state. Therefore, we sought to determine which state, be it acute nicotine abstinence or satiety, would yield the most robust differences compared to non-smokers when assessing neurobiological markers of nicotine dependence. Smokers(N=15) and sociodemographically matched non-smokers(N=15) were scanned twice using a repeated-measures design. Smokers were scanned after a 24-hour nicotine abstinence, and immediately after smoking their usual brand cigarette. The neuroimaging battery included a stop-signal task of response inhibition and pseudo-continuous arterial spin labeling to measure cerebral blood flow (CBF). Whole brain voxel-wise ANCOVAs were carried out on stop success and stop fail SST contrasts and CBF maps to assess differences among non-, abstinent and satiated smokers. Cluster-correction was performed using AFNI's 3dClustSim to achieve a significance of pSmokers exhibited higher brain activation in bilateral inferior frontal gyrus (IFG), a brain region known to be involved in inhibitory control, during successful response inhibitions relative to non-smokers. This effect was significantly higher during nicotine abstinence relative to satiety. Smokers also exhibited lower CBF in the bilateral IFG than non-smokers. These hypo-perfusions were not different between abstinence and satiety. These findings converge on alterations in smokers in prefrontal circuits known to be critical for inhibitory control. These effects are present, even when smokers are satiated, but the neural activity required to achieve performance equal to controls is increased when smokers are in acute abstinence. Our multi-modal neuroimaging study gives neurobiological insights into the cognitive demands of maintaining abstinence and suggest targets for assessing the efficacy of therapeutic interventions.

  13. Microbial Biofertilizer Decreases Nicotine Content by Improving Soil Nitrogen Supply.

    Science.gov (United States)

    Shang, Cui; Chen, Anwei; Chen, Guiqiu; Li, Huanke; Guan, Song; He, Jianmin

    2017-01-01

    Biofertilizers have been widely used in many countries for their benefit to soil biological and physicochemical properties. A new microbial biofertilizer containing Phanerochaete chrysosporium and Bacillus thuringiensis was prepared to decrease nicotine content in tobacco leaves by regulating soil nitrogen supply. Soil NO 3 - -N, NH 4 + -N, nitrogen supply-related enzyme activities, and nitrogen accumulation in plant leaves throughout the growing period were investigated to explore the mechanism of nicotine reduction. The experimental results indicated that biofertilizer can reduce the nicotine content in tobacco leaves, with a maximum decrement of 16-18 % in mature upper leaves. In the meantime, the total nitrogen in mature lower and middle leaves increased with the application of biofertilizer, while an opposite result was observed in upper leaves. Protein concentration in leaves had similar fluctuation to that of total nitrogen in response to biofertilizer. NO 3 - -N content and nitrate reductase activity in biofertilizer-amended soil increased by 92.3 and 42.2 %, respectively, compared to those in the control, whereas the NH 4 + -N and urease activity decreased by 37.8 and 29.3 %, respectively. Nitrogen uptake was improved in the early growing stage, but this phenomenon was not observed during the late growth period. Nicotine decrease is attributing to the adjustment of biofertilizer in soil nitrogen supply and its uptake in tobacco, which result in changes of nitrogen content as well as its distribution in tobacco leaves. The application of biofertilizer containing P. chrysosporium and B. thuringiensis can reduce the nicotine content and improve tobacco quality, which may provide some useful information for tobacco cultivation.

  14. Eningiomas: outcome, and analysis of prognostic factors of primarily resected tumors

    International Nuclear Information System (INIS)

    Stafford, S.L.; Perry, A.; Suman, V.; Meyer, B.; Scheithauer, B.W.; Shaw, E.G.; Earle, J.D.

    1996-01-01

    Purpose: 582 consecutive cases of primary intracranial meningioma undergoing resection at the Mayo Clinic, (Rochester, MN) were reviewed to determine overall survival (OS), progression free survival(PFS), prognostic factors predicting recurrence, and to determine the importance of radiation therapy in the management of this tumor. Materials and Methods: Between 1978-1988, 582 cases of primarily resected meningiomas were identified based on the tumor and operative registries where diagnosis was between 1978-1988 inclusive. PFS was identified by radiographic progression. Follow-up was accomplished by chart review, and a detailed questionnaire sent to patients and referring physicians. Estimation of OS and PFS distributions were done by the Kaplan-Meier method. The log rank test was used to assess which factors were associated with PFS. Proportional hazard modeling was performed to obtain a subset of independent predictors of PFS. Results: the median age was 57(5-93). 67% were female. CT identified the tumor in 91% of cases. There was associated edema in 21% and 2% were radiographically en plaque. There were 17 patients with multiple tumors, four of whom had a known diagnosis of neurofibromatosis. Gross total resection (GTR) was accomplished in 80%, radical subtotal or subtotal resection(STR) in 20%, and biopsy in 53) cellularity, and four or more mitoses per 10 HPF. Multivariate analysis indicated young age, male sex, en plaque at surgery, were significant for decreased PFS when only patient characteristics were considered. When treatment and pathologic factors were also considered, then young age, male sex, less than GTR, and tumor sheeting were predictors for decreased PFS. 10 patients had RT after initial resection, two of whom recurred. There were 107 first recurrences. 50 were observed(no intervention within 3 months), 35 treated by surgery alone, 11 had S+RT, and 11 were treated with RT alone. Considering those patients treated at recurrence (n=57), PFS was at

  15. Analysis of survival for patients with chronic kidney disease primarily related to renal cancer surgery.

    Science.gov (United States)

    Wu, Jitao; Suk-Ouichai, Chalairat; Dong, Wen; Antonio, Elvis Caraballo; Derweesh, Ithaar H; Lane, Brian R; Demirjian, Sevag; Li, Jianbo; Campbell, Steven C

    2018-01-01

    To evaluate predictors of long-term survival for patients with chronic kidney disease primarily due to surgery (CKD-S). Patients with CKD-S have generally good survival that approximates patients who do not have CKD even after renal cancer surgery (RCS), yet there may be heterogeneity within this cohort. From 1997 to 2008, 4 246 patients underwent RCS at our centre. The median (interquartile range [IQR]) follow-up was 9.4 (7.3-11.0) years. New baseline glomerular filtration rate (GFR) was defined as highest GFR between nadir and 6 weeks after RCS. We retrospectively evaluated three cohorts: no-CKD (new baseline GFR of ≥60 mL/min/1.73 m 2 ); CKD-S (new baseline GFR of cancer-related survival (NRCRS) for the CKD-S cohort. Kaplan-Meier analysis assessed the longitudinal impact of new baseline GFR (45-60 mL/min/1.73 m 2 vs <45 mL/min/1.73 m 2 ) and Cox regression evaluated relative impact of preoperative GFR, new baseline GFR, and relevant demographics/comorbidities. Of the 4 246 patients who underwent RCS, 931 had CKD-S and 1 113 had CKD-M/S, whilst 2 202 had no-CKD even after RCS. Partial/radical nephrectomy (PN/RN) was performed in 54%/46% of the patients, respectively. For CKD-S, 641 patients had a new baseline GFR of 45-60 mL/min/1.73 m 2 and 290 had a new baseline GFR of <45 mL/min/1.73 m 2 . Kaplan-Meier analysis showed significantly reduced NRCRS for patients with CKD-S with a GFR of <45 mL/min/1.73 m 2 compared to those with no-CKD or CKD-S with a GFR of 45-60 mL/min/1.73 m 2 (both P ≤ 0.004), and competing risk analysis confirmed this (P < 0.001). Age, gender, heart disease, and new baseline GFR were all associated independently with NRCRS for patients with CKD-S (all P ≤ 0.02). Our data suggest that CKD-S is heterogeneous, and patients with a reduced new baseline GFR have compromised survival, particularly if <45 mL/min/1.73 m 2 . Our findings may have implications regarding choice of PN/RN in patients at risk of developing

  16. NICOTINE-RECEPTOR BLOCKADE AND THE EFFECTS OF ANATOXIN-A ON THE MOTOR ACTIVITY OF RATS: COMPARISON WITH NICOTINE.

    Science.gov (United States)

    Anatoxin-a is produced by several species of freshwater cyanobacteria and has caused several poisoning episodes in terrestrial and aquatic wildlife, livestock and domestic animals. Anatoxin-a is also a potent nicotinic agonist in the nervous system and at the neuromuscular juncti...

  17. 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.

  18. 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

  19. Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization

    Directory of Open Access Journals (Sweden)

    Amanda Clause

    2017-06-01

    Full Text Available Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits. In α9KO mice, the developmental refinement of inhibitory afferents to the lateral superior olive is disturbed, resulting in decreased tonotopic organization of this sound localization nucleus. In this study, we used behavioral tests to investigate whether the circuit anomalies in α9KO mice correlate with sound localization or sound frequency processing. Using a conditioned lick suppression task to measure sound localization, we found that three out of four α9KO mice showed impaired minimum audible angles. Using a prepulse inhibition of the acoustic startle response paradigm, we found that the ability of α9KO mice to detect sound frequency changes was impaired, whereas their ability to detect sound intensity changes was not. These results demonstrate that cholinergic, nicotinic α9 subunit mediated transmission in the developing cochlear plays an important role in the maturation of hearing.

  20. Reducing inflammation and rescuing FTD-related behavioral deficits in progranulin-deficient mice with α7 nicotinic acetylcholine receptor agonists.

    Science.gov (United States)

    Minami, S Sakura; Shen, Vivian; Le, David; Krabbe, Grietje; Asgarov, Rustam; Perez-Celajes, Liberty; Lee, Chih-Hung; Li, Jinhe; Donnelly-Roberts, Diana; Gan, Li

    2015-10-15

    Mutations in the progranulin gene cause frontotemporal dementia (FTD), a debilitating neurodegenerative disease that involves atrophy of the frontal and temporal lobes and affects personality, behavior, and language. Progranulin-deficient mouse models of FTD exhibit deficits in compulsive and social behaviors reminiscent of patients with FTD, and develop excessive microgliosis and increased release of inflammatory cytokines. Activation of nicotinic acetylcholine receptors (nAChRs) by nicotine or specific α7 nAChR agonists reduces neuroinflammation. Here, we investigated whether activation of nAChRs by nicotine or α7 agonists improved the excessive inflammatory and behavioral phenotypes of a progranulin-deficient FTD mouse model. We found that treatment with selective α7 agonists, PHA-568487 or ABT-107, strongly suppressed the activation of NF-κB in progranulin-deficient cells. Treatment with ABT-107 also reduced microgliosis, decreased TNFα levels, and reduced compulsive behavior in progranulin-deficient mice. Collectively, these data suggest that targeting activation of the α7 nAChR pathway may be beneficial in decreasing neuroinflammation and reversing some of the behavioral deficits observed in progranulin-deficient FTD. Copyright © 2015. Published by Elsevier Inc.

  1. 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.

    Science.gov (United States)

    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.

  2. A framework for evaluating the public health impact of e-cigarettes and other vaporized nicotine products.

    Science.gov (United States)

    Levy, David T; Cummings, K Michael; Villanti, Andrea C; Niaura, Ray; Abrams, David B; Fong, Geoffrey T; Borland, Ron

    2017-01-01

    The use of vaporized nicotine products (VNPs), especially e-cigarettes and, to a lesser extent, pressurized aerosol nicotine products and heat-not-burn tobacco products, are being adopted increasingly as an alternative to smoking combusted products, primarily cigarettes. Considerable controversy has accompanied their marketing and use. We propose a framework that describes and incorporates patterns of VNP and combustible cigarette use in determining the total amount of toxic exposure effects on population health. We begin by considering toxicity and the outcomes relevant to population health. We then present the framework and define different measures of VNP use; namely, trial and long-term use for exclusive cigarette smokers, exclusive VNP and dual (cigarette and VNP) use. Using a systems thinking framework and decision theory we considered potential pathways for current, former and never users of VNPs. We then consider the evidence to date and the probable impacts of VNP use on public health, the potential effects of different policy approaches and the possible influence of the tobacco industry on VNP and cigarette use. © 2016 Society for the Study of Addiction.

  3. Nicotine signals through muscle-type and neuronal nicotinic acetylcholine receptors in both human bronchial epithelial cells and airway fibroblasts

    Directory of Open Access Journals (Sweden)

    Luketich James D

    2004-12-01

    Full Text Available Abstract Background Non-neuronal cells, including those derived from lung, are reported to express nicotinic acetylcholine receptors (nAChR. We examined nAChR subunit expression in short-term cultures of human airway cells derived from a series of never smokers, ex-smokers, and active smokers. Methods and Results At the mRNA level, human bronchial epithelial (HBE cells and airway fibroblasts expressed a range of nAChR subunits. In multiple cultures of both cell types, mRNA was detected for subunits that constitute functional muscle-type and neuronal-type pentomeric receptors. Two immortalized cell lines derived from HBE cells also expressed muscle-type and neuronal-type nAChR subunits. Airway fibroblasts expressed mRNA for three muscle-type subunits (α1, δ, and ε significantly more often than HBE cells. Immunoblotting of HBE cell and airway fibroblast extracts confirmed that mRNA for many nAChR subunits is translated into detectable levels of protein, and evidence of glycosylation of nAChRs was observed. Some minor differences in nAChR expression were found based on smoking status in fibroblasts or HBE cells. Nicotine triggered calcium influx in the immortalized HBE cell line BEAS2B, which was blocked by α-bungarotoxin and to a lesser extent by hexamethonium. Activation of PKC and MAPK p38, but not MAPK p42/44, was observed in BEAS2B cells exposed to nicotine. In contrast, nicotine could activate p42/44 in airway fibroblasts within five minutes of exposure. Conclusions These results suggest that muscle-type and neuronal-type nAChRs are functional in airway fibroblasts and HBE cells, that prior tobacco exposure does not appear to be an important variable in nAChR expression, and that distinct signaling pathways are observed in response to nicotine.

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

    Science.gov (United States)

    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.

  5. Chronic ethanol or nicotine treatment results in partial cross-tolerance between these agents.

    Science.gov (United States)

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

    1988-01-01

    Female DBA/2Ibg mice were treated chronically (21 days) with ethanol- or dextrin-containing liquid diets or infused chronically with nicotine (8 mg/kg/h) or saline for 10 days. The responses of these animals to challenge doses of ethanol (2.5 g/kg) or nicotine (1 or 2 mg/kg) were measured using a test battery consisting of respiration rate, acoustic startle response, Y-maze crosses and rears, heart rate and body temperature. Chronic ethanol-treated animals were tolerant to the effects elicited by a challenge dose of ethanol on four of the six measures and were cross-tolerant to nicotine's effects on the acoustic startle test. Chronic nicotine-treated animals were tolerant to nicotine's effects on five of the six measures and cross-tolerant to ethanol's effects on heart rate and body temperature. Thus, partial cross-tolerance between ethanol and nicotine exists. Chronic nicotine treatment resulted in significant increases in L-[3H]-nicotine binding in six of seven brain regions and in alpha-[125I]-bungarotoxin binding in three of seven brain regions. Chronic ethanol treatment failed to alter the binding of either ligand. Therefore, the cross-tolerance that develops between ethanol and nicotine is not totally dependent on alterations in the number of brain nicotinic receptors.

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

    Science.gov (United States)

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

    2018-05-04

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

  7. Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

    Science.gov (United States)

    Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

    2014-04-01

    The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  9. Effects of nicotine on homeostatic and hedonic components of food intake.

    Science.gov (United States)

    Stojakovic, Andrea; Espinosa, Enma P; Farhad, Osman T; Lutfy, Kabirullah

    2017-10-01

    Chronic tobacco use leads to nicotine addiction that is characterized by exaggerated urges to use the drug despite the accompanying negative health and socioeconomic burdens. Interestingly, nicotine users are found to be leaner than the general population. Review of the existing literature revealed that nicotine affects energy homeostasis and food consumption via altering the activity of neurons containing orexigenic and anorexigenic peptides in the brain. Hypothalamus is one of the critical brain areas that regulates energy balance via the action of these neuropeptides. The equilibrium between these two groups of peptides can be shifted by nicotine leading to decreased food intake and weight loss. The aim of this article is to review the existing literature on the effect of nicotine on food intake and energy homeostasis and report on the changes that nicotine brings about in the level of these peptides and their receptors that may explain changes in food intake and body weight induced by nicotine. Furthermore, we review the effect of nicotine on the hedonic aspect of food intake. Finally, we discuss the involvement of different subtypes of nicotinic acetylcholine receptors in the regulatory action of nicotine on food intake and energy homeostasis. © 2017 Society for Endocrinology.

  10. Chronic nicotine differentially alters spontaneous recovery of contextual fear in male and female mice.

    Science.gov (United States)

    Tumolo, Jessica M; Kutlu, Munir Gunes; Gould, Thomas J

    2018-04-02

    Post-traumatic stress disorder (PTSD) is a devastating disorder with symptoms such as flashbacks, hyperarousal, and avoidance of reminders of the traumatic event. Exposure therapy, which attempts to extinguish fear responses, is a commonly used treatment for PTSD but relapse following successful exposure therapy is a frequent problem. In rodents, spontaneous recovery (SR), where extinguished fear responses resurface following extinction treatment, is used as a model of fear relapse. Previous studies from our lab showed that chronic nicotine impaired fear extinction and acute nicotine enhanced SR of contextual fear in adult male mice. In addition, we showed that acute nicotine's effects were specific to SR as acute nicotine did not affect recall of contextual fear conditioning in the absence of extinction. However, effects of chronic nicotine administration on SR are not known. Therefore, in the present study, we investigated if chronic nicotine administration altered SR or recall of contextual fear in adult male and female C57BL/6J mice. Our results showed that chronic nicotine significantly enhanced SR in female mice and significantly decreased SR in males. Chronic nicotine had no effect on recall of contextual fear in males or females. Female sham mice also had significantly less baseline SR than male sham mice. Overall, these results demonstrate sex differences in SR of fear memories and that chronic nicotine modulates these effects on SR but nicotine does not alter recall of contextual fear. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Analysis of effect of nicotine on microbial community structure in sediment using PCR-DGGE fingerprinting

    Directory of Open Access Journals (Sweden)

    Ai-dong Ruan

    2015-10-01

    Full Text Available Solid or liquid waste containing a high concentration of nicotine can pollute sediment in rivers and lakes, and may destroy the ecological balance if it is directly discharged into the environment without any treatment. In this study, the polymerase chain reaction (PCR and denaturing gradient gel electrophoresis (DGGE method was used to analyze the variation of the microbial community structure in the control and nicotine-contaminated sediment samples with nicotine concentration and time of exposure. The results demonstrated that the growth of some bacterial species in the nicotine-contaminated sediment samples was inhibited during the exposure. Some bacteria decreased in species diversity and in quantity with the increase of nicotine concentration or time of exposure, while other bacteria were enriched under the effect of nicotine, and their DGGE bands changed from undertones to deep colors. The microbial community structure, however, showed a wide variation in the nicotine-contaminated sediment samples, especially in the sediment samples treated with high-concentration nicotine. The Jaccard index was only 35.1% between the initial sediment sample and the sediment sample with a nicotine concentration of 0.030 μg/g after 28 d of exposure. Diversity indices showed that the contaminated groups had a similar trend over time. The diversity indices of contaminated groups all decreased in the first 7 d after exposure, then increased until day 42. It has been found that nicotine decreased the diversity of the microbial community in the sediment.

  12. Analysis of effect of nicotine on microbial community structure in sediment using PCR-DGGE fingerprinting

    Directory of Open Access Journals (Sweden)

    Ai-dong Ruan

    2015-10-01

    Full Text Available Solid or liquid waste containing a high concentration of nicotine can pollute sediment in rivers and lakes, and may destroy the ecological balance if it is directly discharged into the environment without any treatment. In this study, the polymerase chain reaction (PCR and denaturing gradient gel electrophoresis (DGGE method was used to analyze the variation of the microbial community structure in the control and nicotine-contaminated sediment samples with nicotine concentration and time of exposure. The results demonstrated that the growth of some bacterial species in the nicotine-contaminated sediment samples was inhibited during the exposure. Some bacteria decreased in species diversity and in quantity with the increase of nicotine concentration or time of exposure, while other bacteria were enriched under the effect of nicotine, and their DGGE bands changed from undertones to deep colors. The microbial community structure, however, showed a wide variation in the nicotine-contaminated sediment samples, especially in the sediment samples treated with high-concentration nicotine. The Jaccard index was only 35.1% between the initial sediment sample and the sediment sample with a nicotine concentration of 0.030 μg/g after 28 d of exposure. Diversity indices showed that the contaminated groups had a similar trend over time. The diversity indices of contaminated groups all decreased in the first 7 d after exposure, then increased until day 42. It has been found that nicotine decreased the diversity of the microbial community in the sediment.

  13. Nicotine anxiogenic and rewarding effects are decreased in mice lacking beta-endorphin.

    Science.gov (United States)

    Trigo, José M; Zimmer, Andreas; Maldonado, Rafael

    2009-06-01

    The endogenous opioid system plays an important role in the behavioral effects of nicotine. Thus, micro-opioid receptor and the endogenous opioids derived from proenkephalin are involved in the central effects of nicotine. However, the role played by the different endogenous opioid peptides in the acute and chronic effects of nicotine remains to be fully established. Mice lacking beta-endorphin were acutely injected with nicotine at different doses to evaluate locomotor, anxiogenic and antinociceptive responses. The rewarding properties of nicotine were evaluated by using the conditioned place-preference paradigm. Mice chronically treated with nicotine were acutely injected with mecamylamine to study the behavioral expression of nicotine withdrawal. Mice lacking beta-endorphin exhibited a spontaneous hypoalgesia and hyperlocomotion and a reduction on the anxiogenic and rewarding effects induced by nicotine. Nicotine induced similar antinociception and hypolocomotion in both genotypes and no differences were found in the development of physical dependence. The dissociation between nicotine rewarding properties and physical dependence suggests a differential implication of beta-endorphin in these addictive related responses.

  14. Nicotine anxiogenic and rewarding effects are decreased in mice lacking β-endorphin

    Science.gov (United States)

    Trigo, José M.; Zimmer, Andreas; Maldonado, Rafael

    2009-01-01

    The endogenous opioid system plays an important role in the behavioral effects of nicotine. Thus, μ-opioid receptor and the endogenous opioids derived from proenkephalin are involved in the central effects of nicotine. However, the role played by the different endogenous opioid peptides in the acute and chronic effects of nicotine remains to be fully established. Mice lacking β-endorphin were acutely injected with nicotine at different doses to evaluate locomotor, anxiogenic and antinociceptive responses. The rewarding properties of nicotine were evaluated by using the conditioned place-preference paradigm. Mice chronically treated with nicotine were acutely injected with mecamylamine to study the behavioral expression of nicotine withdrawal. Mice lacking β-endorphin exhibited a spontaneous hypoalgesia and hyperlocomotion and a reduction on the anxiogenic and rewarding effects induced by nicotine. Nicotine induced similar antinociception and hypolocomotion in both genotypes and no differences were found in the development of physical dependence. The dissociation between nicotine rewarding properties and physical dependence suggests a differential implication of β-endorphin in these addictive related responses. PMID:19376143

  15. Occupational secondhand smoke is the main determinant of hair nicotine concentrations in bar and restaurant workers

    Science.gov (United States)

    Iglesias, Verónica; Erazo, Marcia; Droppelmann, Andrea; Steenland, Kyle; Aceituno, Paulina; Orellana, Cecilia; Acuña, Marisol; Peruga, Armando; Breysse, Patrick N.; Navas-Acien, Ana

    2015-01-01

    Objective To evaluate the relative contribution of occupational vs. non-occupational secondhand tobacco smoke exposure to overall hair nicotine concentrations in non-smoking bar and restaurant employees. Method We recruited 76 non-smoking employees from venues that allowed smoking (n = 9), had mixed policies (smoking and non-smoking areas, n = 13) or were smoke-free (n = 2) between April and August 2008 in Santiago, Chile. Employees used personal air nicotine samplers during working and non-working hours for a 24-h period to assess occupational vs. non-occupational secondhand tobacco smoke exposure and hair nicotine concentrations to assess overall secondhand tobacco smoke exposure. Results Median hair nicotine concentrations were 1.5 ng/mg, interquartile range (IQR) 0.7 to 5.2 ng/mg. Time weighted average personal air nicotine concentrations were higher during working hours (median 9.7, IQR 3.3-25.4 μg/m3) compared to non-working hours (1.7, 1.0-3.1 μg/m3). Hair nicotine concentration was best predicted by personal air nicotine concentration at working hours. After adjustment, a 2-fold increase in personal air nicotine concentration in working hours was associated with a 42% increase in hair nicotine concentration (95% confidence interval 14-70%). Hair nicotine concentration was not associated with personal air nicotine concentration during non-working hours (non-occupational exposure). Conclusions Personal air nicotine concentration at working hours was the major determinant of hair nicotine concentrations in non-smoking employees from Santiago, Chile. Secondhand tobacco smoke exposure during working hours is a health hazard for hospitality employees working in venues where smoking is allowed. PMID:24813578

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

    Science.gov (United States)

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

    2016-12-01

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

  17. Vitamin E and Hippophea rhamnoides L. extract reduce nicotine-induced oxidative stress in rat heart.

    Science.gov (United States)

    Gumustekin, Kenan; Taysi, Seyithan; Alp, Hamit Hakan; Aktas, Omer; Oztasan, Nuray; Akcay, Fatih; Suleyman, Halis; Akar, Sedat; Dane, Senol; Gul, Mustafa

    2010-06-01

    The effects of vitamin E and Hippophea rhamnoides L. extract (HRe-1) on nicotine-induced oxidative stress in rat heart were investigated. There were eight rats per group and supplementation period was 3 weeks. The groups were: nicotine [0.5 mg kg(-1)day(-1), intraperitoneal (i.p.)]; nicotine plus vitamin E [75 mg kg(-1)day(-1), intragastric (i.g.)]; nicotine plus HRe-1 (250 mg kg(-1)day(-1), i.g.); and the control group (receiving only vehicles). Nicotine increased the malondialdehyde level, which was prevented by both vitamin E and HRe-1. Glutathione peroxidase (GPx) activity in nicotine plus vitamin E supplemented group was higher than the others. Glutathione S-transferase (GST) activity in nicotine plus HRe-1 supplemented group was increased compared with the control group. Catalase activity was higher in nicotine group compared with others. GPx activity in nicotine plus vitamin E supplemented group was elevated compared with the others. Total and non-enzymatic superoxide scavenger activities in nicotine plus vitamin E supplemented group were lower than nicotine plus HRe-1 supplemented group. Superoxide dismutase (SOD) activity was higher in nicotine plus HRe-1 supplemented group compared with others. Glutathione reductase activity and nitric oxide level were not affected. Increased SOD and GST activities might have taken part in the prevention of nicotine-induced oxidative stress in HRe-1 supplemented group in rat heart. Flavonols such as quercetin, and isorahmnetin, tocopherols such as alpha-tocopherol and beta-tocopherol and carotenoids such as alpha-carotene and beta-carotene, reported to be present in H. rhamnoides L. extracts may be responsible for the antioxidant effects of this plant extract. 2010 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

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

    2015-07-15

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

  19. Nicotinic acetylcholine receptors controlling attention: Behavior, circuits and sensitivity to disruption by nicotine

    NARCIS (Netherlands)

    Poorthuis, R.B.; Mansvelder, H.D.

    2013-01-01

    Attention is a central cognitive function that enables long-term engagement in a task and suppression of irrelevant information to obtain future goals. The prefrontal cortex (PFC) is the main link in integrating emotional and motivational state of an animal to regulate top-down attentional

  20. 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.

  1. Nicotine promotes cell proliferation via α7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells

    International Nuclear Information System (INIS)

    Wong, Helen Pui Shan; Yu Le; Lam, Emily Kai Yee; Tai, Emily Kin Ki; Wu, William Ka Kei; Cho, Chi Hin

    2007-01-01

    Cigarette smoking has been implicated in colon cancer. Nicotine is a major alkaloid in cigarette smoke. In the present study, we showed that nicotine stimulated HT-29 cell proliferation and adrenaline production in a dose-dependent manner. The stimulatory action of nicotine was reversed by atenolol and ICI 118,551, a β 1 - and β 2 -selective antagonist, respectively, suggesting the role of β-adrenoceptors in mediating the action. Nicotine also significantly upregulated the expression of the catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DβH) and phenylethanolamine N-methyltransferase]. Inhibitor of TH, a rate-limiting enzyme in the catecholamine-biosynthesis pathway, reduced the actions of nicotine on cell proliferation and adrenaline production. Expression of α7-nicotinic acetylcholine receptor (α7-nAChR) was demonstrated in HT-29 cells. Methyllycaconitine, an α7-nAChR antagonist, reversed the stimulatory actions of nicotine on cell proliferation, TH and DβH expression as well as adrenaline production. Taken together, through the action on α7-nAChR nicotine stimulates HT-29 cell proliferation via the upregulation of the catecholamine-synthesis pathway and ultimately adrenaline production and β-adrenergic activation. These data reveal the contributory role α7-nAChR and β-adrenoceptors in the tumorigenesis of colon cancer cells and partly elucidate the carcinogenic action of cigarette smoke on colon cancer

  2. J/Ψ suppression

    International Nuclear Information System (INIS)

    Giubellino, P.; Abreu, M.C.; Alessandro, B.; Alexa, C.; Arnaldi, R.; Astruc, J.; Atayan, M.; Baglin, C.; Baldit, A.; Bedjidian, M.; Bellaiche, F.; Beole, S.; Boldea, V.; Bordalo, P.; Bussiere, A.; Capony, V.; Casagrande, L.; Castor, J.; Chambon, T.; Chaurand, B.; Chevrot, I.; Cheynis, B.; Chiavassa, E.; Cicalo, C.; Comets, M.P.; Constantinescu, S.; Cruz, J.; De Falco, A.; De Marco, N.; Dellacasa, G.; Devaux, A.; Dita, S.; Drapier, O.; Espagnon, B.; Fargeix, J.; Filippov, S.N.; Fleuret, F.; Force, P.; Gallio, M.; Gavrilov, Y.K.; Gerschel, C.; Giubellino, P.; Golubeva, M.B.; Gonin, M.; Grigorian, A.A.; Grossiord, J.Y.; Guber, F.F.; Guichard, A.; Gulkaninan, H.; Hakobyan, R.; Haroutunian, R.; Idzik, M.; Jouan, D.; Karavitcheva, T.L.; Kluberg, L.; Kurepin, A.B.; Le Bornec, Y.; Lourenco, C.; Mac Cormick, M.; Macciotta, P.; Marzari-Chiesa, A.; Masera, M.; Masoni, A.; Mehrabyan, S.; Mourgues, S.; Musso, A.; Ohlsson-Malek, F.; Petiau, P.; Piccotti, A.; Pizzi, J.R.; Prado da Silva, W.L.; Puddu, G.; Quintans, C.; Racca, C.; Ramello, L.; Ramos, S.; Rato-Mendes, P.; Riccati, L.; Romana, A.; Sartori, S.; Saturnini, P.; Scomparin, E.; Serci, S.; Shahoyan, R.; Silva, S.; Soave, C.; Sonderegger, P.; Tarrago, X.; Temnikov, P.; Topilskaya, N.S.; Usai, G.; Vale, C.; Vercellin, E.; Willis, N.

    1999-01-01

    The cross section for J/Ψ production in Pb-Pb interactions at 158 GeV per nucleon is measured at the CERN SPS by the NA50 experiment. The final results from the 1995 run are presented here together with preliminary ones from the high-statistics 1996 run. An anomalous J/Ψ suppression is observed in Pb-Pb collisions as compared to extrapolations of the previous results obtained by the NA38 experiment with proton and lighter ion beams. The results of the two runs are in good agreement. The results from the 1996 run allow the study of the onset of the anomalous suppression within the same set of data, showing evidence of a sharp change of behaviour around a value of neutral transverse energy, as measured by our electromagnetic calorimeter, of about 50 GeV

  3. Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Erfanparast, Amir; Abbas Farshid, Amir; Delkhosh-Kasmaie, Fatmeh

    2017-11-15

    Acetylcholine, as a major neurotransmitter, mediates many brain functions such as pain. This study was aimed to investigate the effects of microinjection of muscarinic and nicotinic acetylcholine receptor antagonists and agonists into the ventrolateral orbital cortex (VLOC) on capsaicin-induced orofacial nociception and subsequent hyperalgesia. The right side of VLOC was surgically implanted with a guide cannula in anaesthetized rats. Orofacial pain-related behaviors were induced by subcutaneous injection of a capsaicin solution (1.5µg/20µl) into the left vibrissa pad. The time spent face rubbing with ipsilateral forepaw and general behavior were recorded for 10min, and then mechanical hyperalgesia was determined using von Frey filaments at 15, 30, 45 and 60min post-capsaicin injection. Alone intra-VLOC microinjection of atropine (a muscarinic acetylcholine receptor antagonist) and mecamylamine (a nicotinic acetylcholine receptor antagonist) at a similar dose of 200ng/site did not alter nocifensive behavior and hyperalgesia. Microinjection of oxotremorine (a muscarinic acetylcholine receptor agonist) at doses of 50 and 100ng/site and epibatidine (a nicotinic acetylcholine receptor agonist) at doses of 12.5, 25, 50 and 100ng/site into the VLOC suppressed pain-related behaviors. Prior microinjections of 200ng/site atropine and mecamylamine (200ng/site) prevented oxotremorine (100ng/site)-, and epibatidine (100ng/site)-induced antinociception, respectively. None of the above-mentioned chemicals changed general behavior. These results showed that the VLOC muscarinic and nicotinic acetylcholine receptors might be involved in modulation of orofacial nociception and hypersensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2014-03-01

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

  5. Nicotine can skew the characterization of the macrophage type-1 (M{Phi}1) phenotype differentiated with granulocyte-macrophage colony-stimulating factor to the M{Phi}2 phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Yanagita, Manabu; Kobayashi, Ryohei [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan); Murakami, Shinya, E-mail: ipshinya@dent.osaka-u.ac.jp [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan)

    2009-10-09

    Macrophages (M{Phi}s) exhibit functional heterogeneity and plasticity in the local microenvironment. Recently, it was reported that M{Phi}s can be divided into proinflammatory M{Phi}s (M{Phi}1) and anti-inflammatory M{Phi}s (M{Phi}2) based on their polarized functional properties. Here, we report that nicotine, the major ingredient of cigarette smoke, can modulate the characteristics of M{Phi}1. Granulocyte-macrophage colony-stimulating factor-driven M{Phi}1 with nicotine (Ni-M{Phi}1) showed the phenotypic characteristics of M{Phi}2. Like M{Phi}2, Ni-M{Phi}1 exhibited antigen-uptake activities. Ni-M{Phi}1 suppressed IL-12, but maintained IL-10 and produced high amounts of MCP-1 upon lipopolysaccharide stimulation compared with M{Phi}1. Moreover, we observed strong proliferative responses of T cells to lipopolysaccharide-stimulated M{Phi}1, whereas Ni-M{Phi}1 reduced T cell proliferation and inhibited IFN-{gamma} production by T cells. These results suggest that nicotine can change the functional characteristics of M{Phi} and skew the M{Phi}1 phenotype to M{Phi}2. We propose that nicotine is a potent regulator that modulates immune responses in microenvironments.

  6. Growth and development, nicotine concentrations and sources of nicotine-n in flue-cured tobacco plants influenced by basal n fertilization time and n fertilizer (15N)

    International Nuclear Information System (INIS)

    Xie Zhijian; Tu Shuxin; Li Jinping; Xu Rubing; Chen Zhenguo; Cao Shiming; Wang Xuelong

    2010-01-01

    A field experiment with 15 N isotope tracing micro-plots was carried out to study the effects of basal N fertilizer application time (15 d, 30 d before the transplanting) of flue-cured tobacco (FCT) seedlings and nitrogen fertilization (with N and without N) on growth and development, nicotine concentrations and sources of nicotine N of FCT in Laowan (N 31 degree 27', E 111 degree 14', 1 130 m above sea level), a main tobacco production area of Xiangfan city, Hubei province. The results showed that both dry matter accumulation and nicotine concentrations of different parts of FCT increased with growing of plants. The concentrations of nicotine decreased with the ascending of leaf position before topping period, but just opposite after the removal of apex. The proportion of nicotine N from fertilizer to total nicotine N decreased with growing of FCT plants and the rising of leaf position. Applying N fertilizer significantly increased dry matter accumulation of shoot and the nicotine concentrations of different poisional tobacco leaves by 2.1-2.7 fold and 0.1-0.7 fold respectively. Compared with the basal fertilization time 15 d before transplanting, applying basal fertilizer 30 d before transplanting increased the dry matter accumulation and nicotine concentrations of flue-cured tobacco by 2.2%-8.0% and 6.3%-18.5% respectively. There was no significant effects of basal N fertilization time on the proportion of nicotine-N from fertilizer in organs of FCT plants at mature stage. These results suggested that properly putting forward the basal N fertilization time before transplanting make for decrease of nicotine concentrations and improvement of quality of FCT leaves, so as to improve its industrial utilities. (authors)

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

    Science.gov (United States)

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

    2018-04-26

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

  8. Nicotine concentrations in urine and saliva of smokers and non-smokers.

    Science.gov (United States)

    Feyerabend, C; Higenbottam, T; Russell, M A

    1982-01-01

    Nicotine concentrations were measured in saliva and urine samples collected from 82 smokers and 56 non-smokers after a morning at work. Each subject answered a series of questions related to their recent intentional or passive exposure to tobacco smoke. All non-smokers had measurable amounts of nicotine in both saliva and urine. Those non-smokers who reported recent exposure to tobacco smoke had significantly higher nicotine concentrations (p less than 0.001) than those who had not been exposed; their concentrations overlapped those of smokers who had smoked up to three cigarettes before sampling had the greatest influence on nicotine concentrations (r=0.62 for saliva and r=0.51 for urine). Neither the nicotine for yield of cigarettes nor the self-reported degree of inhalation had any significant effect on nicotine concentrations. PMID:6802384

  9. A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

    Science.gov (United States)

    Hunter, B E; de Fiebre, C M; Papke, R L; Kem, W R; Meyer, E M

    1994-02-28

    Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain. Xenopus oocyte studies demonstrated that DMXB has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic receptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activation is capable of modulating the induction of long-term potentiation.

  10. Acute effects of high-dose intragastric nicotine on mucosal defense mechanisms

    DEFF Research Database (Denmark)

    Lindell, G; Bukhave, Klaus; Lilja, I

    1997-01-01

    Peptic ulcer disease is overrepresented among smokers; they also heal slowly and relapse frequently. Data are accumulating that smoking is detrimental to gastroduodenal mucosal cytoprotection. This study was designed to assess acute effects of high-dose intragastric nicotine, as it has been shown...... that nicotine is accumulated in gastric juice when smoking, Seven healthy smokers were given nicotine base (6 mg) as tablets, which yielded very high intragastric concentrations and plasma levels comparable to those seen when smoking. In addition to nicotine analysis, concentration levels of prostaglandin E(2......) (PGE(2)), phospholipase A(2) (PLA(2)), and phospholipid classes were measured before and after nicotine administration, Nicotine inhibited PGE(2) levels by 27-81%, whereas PLA(2) and total phospholipids were unaffected. Lysolecithin, a degradation product of the main constituent of gastric surfactant...

  11. Predictive model of nicotine dependence based on mental health indicators and self-concept

    Directory of Open Access Journals (Sweden)

    Hamid Kazemi Zahrani

    2014-12-01

    Full Text Available Background: The purpose of this research was to investigate the predictive power of anxiety, depression, stress and self-concept dimensions (Mental ability, job efficiency, physical attractiveness, social skills, and deficiencies and merits as predictors of nicotine dependency among university students in Isfahan. Methods: In this correlational study, 110 male nicotine-dependent students at Isfahan University were selected by convenience sampling. All samples were assessed by Depression Anxiety Stress Scale (DASS, self-concept test and Nicotine Dependence Syndrome Scale. Data were analyzed by Pearson correlation and stepwise regression. Results: The result showed that anxiety had the highest strength to predict nicotine dependence. In addition, the self-concept and its dimensions predicted only 12% of the variance in nicotine dependence, which was not significant. Conclusion: Emotional processing variables involved in mental health play an important role in presenting a model to predict students’ dependence on nicotine more than identity variables such as different dimensions of self-concept.

  12. Synthesis of 4,4-ditritio-(+)-nicotine: comparative binding and distribution studies with natural enantiomer

    Energy Technology Data Exchange (ETDEWEB)

    Vincek, W.C.; Martin, B.R.; Aceto, M.D.; Tripathi, H.L.; May, E.L.; Harris, L.S.

    1981-11-01

    The preparation of 4,4-ditritio-(+)-nicotine (Vb) (specific activity 10.3 Ci/mmole)from (+)-nicotine (Ib) via (-) 4,4-dibromocotinine (IIIb) is described. Although Ib is 10-30 times less potent than (-)-nicotine (Ia) in the CNS, its binding affinity for the crude mitochondrial or nuclear fraction of whole rat brain is only three times less than that of Ia. However, distribution studies showed that the maximum brain levels of (-)-(3H) nicotine are nearly twice those of (+)-(3H)-nicotine following administration of a 2-micrograms/kg dose. Binding affinity and disposition of the stereoisomers account for a portion of the pharmacological stereospecificity of nicotine.

  13. The Yin and Yang of nicotine: harmful during development, beneficial in adult patient populations

    Directory of Open Access Journals (Sweden)

    Danielle S Counotte

    2012-10-01

    Full Text Available Nicotine has remarkably diverse effects on the brain. Being the main active compound in tobacco, nicotine can aversively affect brain development. However, it has the ability to act positively by restoring attentional capabilities in smokers. Here, we focus on nicotine exposure during the prenatal and adolescent developmental periods and specifically, we will review the long-lasting effects of nicotine on attention, both in humans and animal models. We discuss the reciprocal relation of the beneficial effects of nicotine, improving attention in smokers and in patients with neuropsychiatric diseases, such as schizophrenia and attention deficit/hyperactivity disorder, versus nicotine-related attention deficits already caused during adolescence. Given the need for research on the mechanisms of nicotine’s cognitive actions, we discuss some of the recent work performed in animals.

  14. 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.

  15. Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments.

    Science.gov (United States)

    D'Souza, Manoranjan S; Markou, Athina

    2011-07-01

    Tobacco smoking causes high rates of mortality and morbidity throughout the world. Despite the availability of smoking-cessation medications, maintenance of long-term abstinence is difficult, and most individuals who attempt to quit smoking relapse. Although tobacco smoke contains many substances, researchers and policymakers agree that nicotine is a major cause of tobacco dependence. Understanding the neural substrates of nicotine dependence is essential for the development of more effective antismoking medications than those currently available. This article focuses on the neural substrates, especially nicotinic acetylcholine receptors, that mediate the reinforcing effects of nicotine and the development of nicotine dependence. Neuroadaptations in the function of the neurotransmitters dopamine, glutamate, and gamma-aminobutyric acid (GABA), which have been shown to be critically involved in nicotine dependence, are also reviewed. Finally, the article discusses progress in the discovery and development of smoking-cessation medications.

  16. Nicotine yesterday, today, and tomorrow: a global review.

    Science.gov (United States)

    Gray, Nigel J

    2014-02-01

    This intentionally selective global review reflects the views and frustrations of a public health physician with 45 years of frontline experience in tobacco control. In particular, it focuses on the nexus between research and policy and the long periods between relevant discoveries and application as policy. Consideration is given to the relative neglect of the possibility of reducing the carcinogenicity and toxicity of the cigarette on the grounds that it is the preferred source of nicotine for the global majority of nicotine users. Although the outcome of such change is unquantifiable, there is much in cigarette smoke that can be changed to make it less carcinogenic and less toxic. It is difficult to think of excuses for accepting the status quo.

  17. Electronic cigarettes: health impact, nicotine replacement therapy, regulations

    Directory of Open Access Journals (Sweden)

    Zygmunt Zdrojewicz

    2017-03-01

    Full Text Available While the adverse effects of conventional cigarettes on human health have been thoroughly examined, in the last 15 years we have witnessed the birth of electronic cigarettes. There are many types of these devices available on the market. Studies are still underway to determine their negative impact on the human body. Electronic cigarettes comprise of power supply and a vaporising system. The user inhales the aerosol produced by heating up the liquid containing nicotine. In contrast with conventional cigarettes, the tobacco is not combusted, thus the compositions of the aerosol and cigarette smoke are considerably different. Out of 93 chemical substances present in the e-cigarette smoke, the aerosol contains only acetaldehyde, acetone, acrolein, formaldehyde and nicotine. More toxic substances, such as polycyclic aromatic hydrocarbons and heavy metals, are not present. The amount of evidence suggesting electronic cigarettes’ harmful effects on the human body is constantly increasing. Some reports imply that the electronic cigarettes negatively influence pregnancy, human psyche, respiratory and cardiovascular systems. They might also be involved in oncogenesis. With electronic cigarettes constantly gaining popularity, the question about the adverse effects of passive smoking becomes increasingly more relevant. Although various methods of helping people cease smoking or delivering nicotine to their bodies without burning toxic substances are being explored, electronic cigarettes are not recommended in nicotine substitution therapy. Legal regulations regarding electronic cigarettes are still being worked on. The purpose of this paper is to evaluate the effects electronic cigarettes have on the human’s health.

  18. Nicotine supplementation blocks oocyte maturation in Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Meitria Syahadatina Noor

    2013-08-01

    Full Text Available Background Indonesia has the third largest tobacco consumption in the world after China and India. Nicotine as the main component of cigarette smoke has negative effects on the reproductive system, such as oocyte maturation, ovulation, and fertilization, and increasing the diploidy of oocytes. The goal of this research was to evaluate the effect of nicotine on oocyte maturation in Rattus norvegicus. Methods This was an experimental study with post test only control group design. The subjects were 40 rats selected homogenously and randomly. They were divided into a control group (receiving carboxy-methyl-cellulose sodium and 3 treatment groups (I-III receiving nicotine subcutaneously for 7 days at dosages of 21 mg/kgBW, 41 kg/kgBW and 84/kgBW, respectively. The observations comprised oocyte maturation stage, viz. germinal vesicle (GV, germinal vesicle breakdown (GVBD, metaphase I and metaphase II. Data were analyzed by one-way Anova with á=0.05, followed by Tukey’s HSD test. Results One-way Anova showed significant differences in oocyte maturation in all groups. Tukey’s HSD test showed that for GV, the differing groups were control and I, control and II, I and III. For GVBD, the differing groups were control and I, I and II, I and III. For metaphase I, the differing groups were control with I, II, and III, I and II, I and III. For metaphase II, the differing groups were control versus I, II, and III, I and II, I and III. Conclusion Low dose of nicotine is capable of affecting oocyte maturation in Rattus norvegicus.

  19. Allosteric modulation of the nicotinic acetylcholine receptor by physostigmine

    Czech Academy of Sciences Publication Activity Database

    Svobodová, Lucie; Krůšek, Jan; Hendrych, Tomáš; Vyskočil, František

    2005-01-01

    Roč. 1048, - (2005), s. 355-358 ISSN 0077-8923 R&D Projects: GA ČR(CZ) GA202/02/1213; GA ČR(CZ) GA305/02/1333; GA ČR(CZ) GD305/03/H148 Institutional research plan: CEZ:AV0Z5011922 Keywords : nicotinic ACh receptor * serine * desensitization Subject RIV: ED - Physiology Impact factor: 1.971, year: 2005

  20. Revisiting nicotine's role in the ageing brain and cognitive impairment

    DEFF Research Database (Denmark)

    Majdi, Alireza; Kamari, Farzin; Vafaee, Manouchehr Seyedi

    2017-01-01

    Brain ageing is a complex process which in its pathologic form is associated with learning and memory dysfunction or cognitive impairment. During ageing, changes in cholinergic innervations and reduced acetylcholinergic tonus may trigger a series of molecular pathways participating in oxidative...... in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment....

  1. Gutkha Addiction: Nicotine Dependence or a Conditioned Reflex?

    OpenAIRE

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