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Sample records for chronic nicotine selectively

  1. 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

  2. Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.

    Science.gov (United States)

    Rezvani, Amir H; Cauley, Marty; Xiao, Yingxian; Kellar, Kenneth J; Levin, Edward D

    2013-03-01

    Nicotine and nicotinic agonists have been shown to improve attentional function. Nicotinic receptors are easily desensitized, and all nicotinic agonists are also desensitizing agents. Although both receptor activation and desensitization are components of the mechanism that mediates the overall effects of nicotinic agonists, it is not clear how each of the two opposed actions contributes to attentional improvements. Sazetidine-A has high binding affinity at α4β2 nicotinic receptors and causes a relatively brief activation followed by a long-lasting desensitization of the receptors. Acute administration of sazetidine-A has been shown to significantly improve attention by reversing impairments caused by the muscarinic cholinergic antagonist scopolamine and the NMDA glutamate antagonist dizocilpine. In the current study, we tested the effects of chronic subcutaneous infusion of sazetidine-A (0, 2, or 6 mg/kg/day) on attention in Sprague-Dawley rats. Furthermore, we investigated the effects of chronic sazetidine-A treatment on attentional impairment induced by an acute administration of 0.02 mg/kg scopolamine. During the first week period, the 6-mg/kg/day sazetidine-A dose significantly reversed the attentional impairment induced by scopolamine. During weeks 3 and 4, the scopolamine-induced impairment was no longer seen, but sazetidine-A (6 mg/kg/day) significantly improved attentional performance on its own. Chronic sazetidine-A also reduced response latency and response omissions. This study demonstrated that similar to its acute effects, chronic infusions of sazetidine-A improve attentional performance. The results indicate that the desensitization of α4β2 nicotinic receptors with some activation of these receptors may play an important role in improving effects of sazetidine-A on attention.

  3. 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

  4. 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

  5. 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...

  6. 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.

  7. 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...

  8. Does chronic nicotine alter neurotransmitter receptors involved in Parkinson's disease?

    International Nuclear Information System (INIS)

    Reilly, M.A.; Lapin, E.P.; Lajtha, A.; Maker, H.S.

    1986-01-01

    Cigarette smokers are fewer in number among Parkinson's Disease (PD) patients than among groups of persons who do not have PD. Several hypotheses have been proposed to explain this observation. One which must be tested is the possibility that some pharmacologic agent present in cigarette smoke may interact with some central nervous system component involved in PD. To this end, they have investigated the effect of chronic nicotine administration on receptors for some of the neurotransmitters that are affected in PD. Rats were injected for six weeks with saline or nicotine 0.8 mg/kg S.C., then killed and brains removed and dissected. The binding of ( 3 H)-ketanserin to serotonin receptors in frontal cortex and of ( 3 H)-domperidone to dopamine receptors in caudate was not affected. However, the binding of ( 3 H)-domperidone in nucleus accumbens was altered: the K/sub d/ increased from 0.16 +/- 0.02 nM to 0.61 +/- 0.07 nM, and the B/sub max/ increased from 507 +/- 47 fmol/mg protein to 910 +/- 43 fmol/mg (p < 0.001 for both comparisons). These values are based on three ligand concentrations. Additional studies are in progress to substantiate the data. It is concluded that chronic nicotine administration may alter dopamine receptors in nucleus accumbens

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

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    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.

  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. 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.

  12. 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....

  13. 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.

  14. Smoking history, nicotine dependence and opioid use in patients with chronic non-malignant pain

    DEFF Research Database (Denmark)

    Plesner, K; Jensen, H I; Højsted, J

    2016-01-01

    doses than never smokers and former smokers not using nicotine. CONCLUSIONS: The study supports previous evidence that smoking is associated with chronic pain. Our data suggest that information about use of nicotine substitution in chronic non-malignant patients are relevant both in a clinical setting......BACKGROUND: Previous studies have demonstrated a positive association between smoking and addiction to opioids in patients with chronic non-malignant pain. This could be explained by a susceptibility in some patients to develop addiction. Another explanation could be that nicotine influences both...... pain and the opioid system. The objective of the study was to investigate whether smoking, former smoking ± nicotine use and nicotine dependence in patients with chronic non-malignant pain were associated with opioid use and addiction to opioids. METHODS: The study was a cross-sectional study carried...

  15. 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.

  16. 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

  17. Exposure to chronic mild stress prevents kappa opioid-mediated reinstatement of cocaine and nicotine place preference

    Directory of Open Access Journals (Sweden)

    Ream eAl-Hasani

    2013-08-01

    Full Text Available Stress increases the risk of drug abuse, causes relapse to drug seeking, and potentiates the rewarding properties of both nicotine and cocaine. Understanding the mechanisms by which stress regulates the rewarding properties of drugs of abuse provides valuable insight into potential treatments for drug abuse. Prior reports have demonstrated that stress causes dynorphin release, activating kappa-opioid receptors (KOR in monoamine circuits resulting in both potentiation and reinstatement of cocaine and nicotine conditioned place preference. Here we report that kappa-opioid dependent reinstatement of cocaine and nicotine place preference is reduced when the mice are exposed to a randomized chronic mild stress regime prior to training in a conditioned place preference-reinstatement paradigm. The chronic mild stress schedule involves seven different stressors (removal of nesting for 24hr, 5min forced swim stress at 15°C, 8hr food and water deprivation, damp bedding overnight, white noise, cage tilt and disrupted home cage lighting rotated over a three-week period. This response is KOR-selective, because chronic mild stress does not protect against cocaine or nicotine drug-primed reinstatement. This protection from reinstatement is also observed following sub-chronic social defeat stress, where each mouse is placed in an aggressor mouse home cage for a period of 20 min over five days. In contrast, a single acute stressor resulted in a potentiation of KOR-induced reinstatement, similarly to previously reported. Prior studies have shown that stress alters sensitivity to opioids and prior stress can influence the pharmacodynamics of the opioid receptor system. Together, these findings suggest that exposure to different forms of stress may cause a dysregulation of kappa opioid circuitry and that changes resulting from mild stress can have protective and adaptive effects against drug relapse.

  18. Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice.

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    Shang, Xueliang; Shang, Yingchun; Fu, Jingxuan; Zhang, Tao

    2017-08-01

    The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild stress (CUMS) and isolated feeding. Mice were exposed to CUMS continued for 28 days, while nicotine (0.2 mg/kg) was also administrated for 28 days. Weight and sucrose consumption were measured during model establishing period. The anxiety and behavioral despair were analyzed using the forced swim test (FST) and open-field test (OFT). Spatial cognition was evaluated using Morris water maze (MWM) test. Following behavioral assessment, both long-term potentiation (LTP) and depotentiation (DEP) were recorded in the hippocampal dentate gyrus (DG) region. Both synaptic and Notch1 proteins were measured by Western. Nicotine increased stressed mouse's sucrose consumption. The MWM test showed that spatial learning and reversal learning in stressed animals were remarkably affected relative to controls, whereas nicotine partially rescued cognitive functions. Additionally, nicotine considerably alleviated the level of anxiety and the degree of behavioral despair in stressed mice. It effectively mitigated the depression-induced impairment of hippocampal synaptic plasticity, in which both the LTP and DEP were significantly inhibited in stressed mice. Moreover, nicotine enhanced the expression of synaptic and Notch1 proteins in stressed animals. The results suggest that nicotine ameliorates the depression-like symptoms and improves the hippocampal synaptic plasticity closely associated with activating transmembrane ion channel receptors and Notch signaling components. Graphical Abstract ᅟ.

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2017-07-03

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

  1. Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation.

    Science.gov (United States)

    Lam, Sum; Patel, Priti N

    2007-01-01

    Tobacco smoking remains a significant health problem in the United States. It has been associated with staggering morbidity and mortality, specifically due to malignancies and cardiovascular disease. Smoking cessation can be difficult and frequently requires pharmacologic interventions in addition to nonpharmacologic measures. Previously available agents are nicotine replacement products and bupropion, which increased quit rates by about 2-fold compared with placebo. Varenicline is the first drug in a new class known as the selective alpha4beta2 nicotinic receptor partial agonists. In several randomized, double-blind, 52-week clinical trials involving healthy chronic smokers, varenicline demonstrated superiority to placebo and bupropion in terms of efficacy measures. Additionally, it improved tobacco withdrawal symptoms and reinforcing effects of smoking in relapsed patients. Patients should start therapy in combination with tobacco cessation counseling 1 week before quit date and continue the regimen for 12 weeks. The dose of varenicline should be titrated to minimize nausea. The recommended dosage is 0.5 mg once daily (QD) on days 1-3; titrate to 0.5 mg twice daily (BID) on days 4-7; and 1 mg BID starting on day 8. An additional 12-week maintenance therapy may be considered for those who achieve abstinence. The most common side effects are nausea (30%), insomnia (18%), headache (15%), abnormal dreams (13%), constipation (8%), and abdominal pain (7%). Overall, varenicline is a breakthrough in the management of tobacco addiction and has demonstrated good efficacy in motivated quitters. It also provides an option for smokers who cannot tolerate other pharmacologic interventions.

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

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

    2002-06-01

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

  3. Particle size distribution of selected electronic nicotine delivery system products.

    Science.gov (United States)

    Oldham, Michael J; Zhang, Jingjie; Rusyniak, Mark J; Kane, David B; Gardner, William P

    2018-03-01

    Dosimetry models can be used to predict the dose of inhaled material, but they require several parameters including particle size distribution. The reported particle size distributions for aerosols from electronic nicotine delivery system (ENDS) products vary widely and don't always identify a specific product. A low-flow cascade impactor was used to determine the particle size distribution [mass median aerodynamic diameter (MMAD); geometric standard deviation (GSD)] from 20 different cartridge based ENDS products. To assess losses and vapor phase amount, collection efficiency of the system was measured by comparing the collected mass in the impactor to the difference in ENDS product mass. The levels of nicotine, glycerin, propylene glycol, water, and menthol in the formulations of each product were also measured. Regardless of the ENDS product formulation, the MMAD of all tested products was similar and ranged from 0.9 to 1.2 μm with a GSD ranging from 1.7 to 2.2. There was no consistent pattern of change in the MMAD and GSD as a function of number of puffs (cartridge life). The collection efficiency indicated that 9%-26% of the generated mass was deposited in the collection system or was in the vapor phase. The particle size distribution data are suitable for use in aerosol dosimetry programs. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

    Okoli, Chizimuzo; Kodet, Jonathan; Robertson, Heather

    2016-01-01

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

  5. Nicotine reverses anhedonic-like response and cognitive impairment in the rat chronic mild stress model of depression

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Henningsen, Kim; Bate, Simon

    2011-01-01

    Smoking rates among depressed individuals are higher than is observed in the background population, and nicotine alleviates depressive symptoms. In rodents, nicotine shows antidepressant-like effects in the forced swim and learned helplessness paradigms. Clinical depression is associated with both...... anhedonia and cognitive impairments. In rats, chronic mild stress (CMS) decreases voluntary sucrose intake, reflecting an anhedonic-like state, and impairs performance in the spontaneous alternation behaviour (SAB) test, suggesting impaired cognitive function. Here, we examine the effect of chronic...... with depression....

  6. Performance effects of nicotine during selective attention, divided attention, and simple stimulus detection: an fMRI study.

    Science.gov (United States)

    Hahn, Britta; Ross, Thomas J; Wolkenberg, Frank A; Shakleya, Diaa M; Huestis, Marilyn A; Stein, Elliot A

    2009-09-01

    Attention-enhancing effects of nicotine appear to depend on the nature of the attentional function. Underlying neuroanatomical mechanisms, too, may vary depending on the function modulated. This functional magnetic resonance imaging study recorded blood oxygen level-dependent (BOLD) activity in minimally deprived smokers during tasks of simple stimulus detection, selective attention, or divided attention after single-blind application of a transdermal nicotine (21 mg) or placebo patch. Smokers' performance in the placebo condition was unimpaired as compared with matched nonsmokers. Nicotine reduced reaction time (RT) in the stimulus detection and selective attention but not divided attention condition. Across all task conditions, nicotine reduced activation in frontal, temporal, thalamic, and visual regions and enhanced deactivation in so-called "default" regions. Thalamic effects correlated with RT reduction selectively during stimulus detection. An interaction with task condition was observed in middle and superior frontal gyri, where nicotine reduced activation only during stimulus detection. A visuomotor control experiment provided evidence against nonspecific effects of nicotine. In conclusion, although prefrontal activity partly displayed differential modulation by nicotine, most BOLD effects were identical across tasks, despite differential performance effects, suggesting that common neuronal mechanisms can selectively benefit different attentional functions. Overall, the effects of nicotine may be explained by increased functional efficiency and downregulated task-independent "default" functions.

  7. Design of ligands for the nicotinic acetylcholine receptors: the quest for selectivity.

    Science.gov (United States)

    Bunnelle, William H; Dart, Michael J; Schrimpf, Michael R

    2004-01-01

    In the last decade, nicotinic acetylcholine receptors (nAChRs) have emerged as important targets for drug discovery. The therapeutic potential of nicotinic agonists depends substantially on the ability to selectively activate certain receptor subtypes that mediate beneficial effects. The design of such compounds has proceeded in spite of a general shortage of data pertaining to subtype selectivity. Medicinal chemistry efforts have been guided principally by binding affinities to the alpha4beta2 and/or alpha7 subtypes, even though these are not predictive of agonist activity at either subtype. Nevertheless, a diverse family of nAChR ligands has been developed, and several analogs with promising therapeutic potential have now advanced to human clinical trials. This paper provides an overview of the structure-affinity relationships that continue to drive development of new nAChR ligands.

  8. Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin Uptake by Pancreatic Acinar Cells.

    Directory of Open Access Journals (Sweden)

    Padmanabhan Srinivasan

    Full Text Available Thiamin (vitamin B1, a member of the water-soluble family of vitamins, is essential for normal cellular functions; its deficiency results in oxidative stress and mitochondrial dysfunction. Pancreatic acinar cells (PAC obtain thiamin from the circulation using a specific carrier-mediated process mediated by both thiamin transporters -1 and -2 (THTR-1 and THTR-2; encoded by the SLC19A2 and SLC19A3 genes, respectively. The aim of the current study was to examine the effect of chronic exposure of mouse PAC in vivo and human PAC in vitro to nicotine (a major component of cigarette smoke that has been implicated in pancreatic diseases on thiamin uptake and to delineate the mechanism involved. The results showed that chronic exposure of mice to nicotine significantly inhibits thiamin uptake in murine PAC, and that this inhibition is associated with a marked decrease in expression of THTR-1 and THTR-2 at the protein, mRNA and hnRNAs level. Furthermore, expression of the important thiamin-metabolizing enzyme, thiamin pyrophosphokinase (TPKase, was significantly reduced in PAC of mice exposed to nicotine. Similarly, chronic exposure of cultured human PAC to nicotine (0.5 μM, 48 h significantly inhibited thiamin uptake, which was also associated with a decrease in expression of THTR-1 and THTR-2 proteins and mRNAs. This study demonstrates that chronic exposure of PAC to nicotine impairs the physiology and the molecular biology of the thiamin uptake process. Furthermore, the study suggests that the effect is, in part, mediated through transcriptional mechanism(s affecting the SLC19A2 and SLC19A3 genes.

  9. Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.

    Science.gov (United States)

    Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R; Hecht, Sidney M; Chang, Yung

    2017-05-08

    Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC 50 ) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and

  10. 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.

  11. 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/.

  12. Changes in the α4β2* nicotinic acetylcholine system during chronic controlled alcohol exposure in nonhuman primates.

    Science.gov (United States)

    Hillmer, Ansel T; Tudorascu, Dana L; Wooten, Dustin W; Lao, Patrick J; Barnhart, Todd E; Ahlers, Elizabeth O; Resch, Leslie M; Larson, Julie A; Converse, Alexander K; Moore, Colleen F; Schneider, Mary L; Christian, Bradley T

    2014-05-01

    The precise nature of modifications to the nicotinic acetylcholine receptor (nAChR) system in response to chronic ethanol exposure is poorly understood. The present work used PET imaging to assay α4β2* nAChR binding levels of eight rhesus monkeys before and during controlled chronic ethanol intake. [(18)F]Nifene PET scans were conducted prior to alcohol exposure, and then again after at least 8 months controlled ethanol exposure, including 6 months at 1.5 g/kg/day following a dose escalation period. Receptor binding levels were quantified with binding potentials (BPND) using the cerebellum as a reference region. Alcohol self-administration was assessed as average daily alcohol intake during a 2 month free drinking period immediately following controlled alcohol. Significant decreases in α4β2* nAChR binding were observed in both frontal and insular cortex in response to chronic ethanol exposure. During chronic alcohol exposure, BPND in the lateral geniculate region correlated positively with the amount of alcohol consumed during free drinking. The observed decreases in nAChR availability following chronic alcohol consumption suggest alterations to this receptor system in response to repeated alcohol administration, making this an important target for further study in alcohol abuse and alcohol and nicotine codependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. 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.

  14. In vivo effect of chronic nicotine exposure on outcome of Plasmodium berghei ANKA malaria

    Directory of Open Access Journals (Sweden)

    Tsige Ketema

    2017-04-01

    Full Text Available Objective: To assess effect of nicotine, major addictive component of tobacco smoke, on outcomes of the deadly malaria parasite using mice as animal model. Methods: Male Swiss albino mice were treated with 100 and 200 µg/mL of nicotine in drinking water daily for 6 weeks followed by Plasmodium berghei ANKA (PbA infection. On the seventh day of post infection (p.i., physical, clinical, histopathological, biochemical and hematological parameters were assessed. Data were analyzed using SPSS software. Results: Nicotine was significantly (P < 0.05 positively associated with lower levels of hemoglobin (Hb, hematocrit (HCT, red blood cells (RBCs, C-reactive protein (CRP and uric acid (UA, higher risk to incidence of pulmonary edema, elevated level of liver and kidney biomarkers. Also significant increment (P < 0.01 of monocyte-lymphocyte count ratio (MLCR was observed. Risk to high temperature, lower platelet count, high parastemia and cerebral malaria was lesser in mice treated with nicotine (100 and 200 µg/mL followed by PbA infection than the positive control. Lack of neurological symptoms might be accounted to the anti-inflammatory property of nicotine that could inhibit production of pro-inflammatory mediators responsible for occurrence of cerebral malaria. Conclusions: This study showed that despite down regulation of most cerebral malaria symptoms nicotine was strongly associated with increased risk to most clinical symptoms of malaria. Thus, like in respiratory infections, nicotine use might enhance susceptibility to malaria.

  15. Changes in orexinergic immunoreactivity of the piglet hypothalamus and pons after exposure to chronic postnatal nicotine and intermittent hypercapnic hypoxia.

    Science.gov (United States)

    Hunt, Nicholas J; Russell, Benjamin; Du, Man K; Waters, Karen A; Machaalani, Rita

    2016-06-01

    We recently showed that orexin expression in sudden infant death syndrome (SIDS) infants was reduced by 21% in the hypothalamus and by 40-50% in the pons as compared with controls. Orexin maintains wakefulness/sleeping states, arousal, and rapid eye movement sleep, abnormalities of which have been reported in SIDS. This study examined the effects of two prominent risk factors for SIDS, intermittent hypercapnic hypoxia (IHH) (prone-sleeping) and chronic nicotine exposure (cigarette-smoking), on orexin A (OxA) and orexin B (OxB) expression in piglets. Piglets were randomly assigned to five groups: saline control (n = 7), air control (n = 7), nicotine [2 mg/kg per day (14 days)] (n = 7), IHH (6 min of 7% O2 /8% CO2 alternating with 6-min periods of breathing air, for four cycles) (n = 7), and the combination of nicotine and IHH (N + IHH) (n = 7). OxA/OxB expression was quantified in the central tuberal hypothalamus [dorsal medial hypothalamus (DMH), perifornical area (PeF), and lateral hypothalamus], and the dorsal raphe, locus coeruleus of the pons. Nicotine and N + IHH exposures significantly increased: (i) orexin expression in the hypothalamus and pons; and (ii) the total number of neurons in the DMH and PeF. IHH decreased orexin expression in the hypothalamus and pons without changing neuronal numbers. Linear relationships existed between the percentage of orexin-positive neurons and the area of pontine orexin immunoreactivity of control and exposure piglets. These results demonstrate that postnatal nicotine exposure increases the proportion of orexin-positive neurons in the hypothalamus and fibre expression in the pons, and that IHH exposure does not prevent the nicotine-induced increase. Thus, although both nicotine and IHH are risk factors for SIDS, it appears they have opposing effects on OxA and OxB expression, with the IHH exposure closely mimicking what we recently found in SIDS. © 2016 Federation of European Neuroscience Societies and John

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

    Science.gov (United States)

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

    2015-05-05

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

  17. Chronic nicotine-induced changes in gene expression of delta and kappa-opioid receptors and their endogenous ligands in the mesocorticolimbic system of the rat.

    Science.gov (United States)

    Ugur, Muzeyyen; Kaya, Egemen; Gozen, Oguz; Koylu, Ersin O; Kanit, Lutfiye; Keser, Aysegul; Balkan, Burcu

    2017-09-01

    Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are proposed as important mediators of nicotine reward. This study investigated the regulatory effect of chronic nicotine treatment on the gene expression of DOR, KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were injected subcutaneously with nicotine at doses of 0.2, 0.4, or 0.6 mg/kg/day for 6 days. Rats were decapitated 1 hr after the last dose on day six, as this timing coincides with increased dopamine release in the mesocorticolimbic system. mRNA levels in the ventral tegmental area (VTA), lateral hypothalamic area (LHA), amygdala (AMG), dorsal striatum (DST), nucleus accumbens, and medial prefrontal cortex were measured by quantitative real-time PCR. Our results showed that nicotine upregulated DOR mRNA in the VTA at all of the doses employed, in the AMG at the 0.4 and 0.6 mg/kg doses, and in the DST at the 0.4 mg/kg dose. Conversely, PDYN mRNA was reduced in the LHA with 0.6 mg/kg nicotine and in the AMG with 0.4 mg/kg nicotine. KOR mRNA was also decreased in the DST with 0.6 mg/kg nicotine. Nicotine did not regulate PENK mRNA in any brain region studied. © 2017 Wiley Periodicals, Inc.

  18. Withdrawal from chronic exposure to amphetamine, but not nicotine, leads to an immediate and enduring deficit in motivated behavior without affecting social interaction in rats

    OpenAIRE

    Der-Avakian, Andre; Markou, Athina

    2010-01-01

    Psychostimulant withdrawal leads to depressive symptoms, such as anhedonia and social dysfunction. We determined the effects of withdrawal from chronic exposure to nicotine (9 mg/kg/day salt, 28 days) or amphetamine (10 mg/kg/day salt, 7 days) on the motivated response for a sucrose reward and on social interaction in rats. Both nicotine and amphetamine exposure increased the motivated response for sucrose. However, only spontaneous amphetamine withdrawal led to an immediate and persistent de...

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

    OpenAIRE

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

    2016-01-01

    Background The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells. Methods Mice were exposed to aerosolised phosphate-buf...

  20. Molecular determinants of subtype-selective efficacies of cytisine and the novel compound NS3861 at heteromeric nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Harpsøe, Kasper; Hald, Helle; Timmermann, Daniel B

    2013-01-01

    Deciphering which specific agonist-receptor interactions affect efficacy levels is of high importance, because this will ultimately aid in designing selective drugs. The novel compound NS3861 and cytisine are agonists of nicotinic acetylcholine receptors (nAChRs) and both bind with high affinity...

  1. 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

  2. A comparison of the development of tolerance to ethanol and cross-tolerance to nicotine after chronic ethanol treatment in long- and short-sleep mice.

    Science.gov (United States)

    de Fiebre, C M; Collins, A C

    1993-09-01

    Previous studies have shown that inbred mouse strains differ in the development of tolerance to both nicotine and ethanol, indicating that genetic factors regulate tolerance development. Those mouse strains that are most sensitive to an acute challenge dose of either drug develop the most tolerance to that drug. The ethanol-sensitive long-sleep (LS) mice are more sensitive to several behavioral and physiological effects of nicotine than are the ethanol-resistant short-sleep (SS) mice. The experiments reported here assessed whether the LS and SS mice develop tolerance to ethanol after chronic treatment with ethanol-containing liquid diets and whether cross-tolerance to nicotine also developed. Tolerance and cross-tolerance were measured by assessing the effects of acute challenge doses of drug on Y-maze crossing and rearing activities, heart rate and body temperature. The LS mice developed tolerance to ethanol's effects on three of the four measures and were cross-tolerant to nicotine on all of the measures. In contrast, the SS mice developed tolerance to ethanol for only two of the measures, but failed to develop cross-tolerance to any action of nicotine. These findings support the hypothesis that ethanol and nicotine share sites of action and that common genes regulate responses to these two drugs. Evidence suggests that tolerance to nicotine may be related to an up-regulation of brain nicotinic receptors, at least in some inbred mouse strains, but chronic ethanol treatment did not reproducibly change either [3H]nicotine or alpha-[125I]bungarotoxin binding. Therefore, other mechanisms must underlie the tolerance and cross-tolerance that was seen.

  3. Adolescent chronic variable social stress influences exploratory behavior and nicotine responses in male, but not female, BALB/cJ mice.

    Science.gov (United States)

    Caruso, M J; Reiss, D E; Caulfield, J I; Thomas, J L; Baker, A N; Cavigelli, S A; Kamens, H M

    2018-04-01

    Anxiety disorders and nicotine use are significant contributors to global morbidity and mortality as independent and comorbid diseases. Early-life stress, potentially via stress-induced hypothalamic-pituitary-adrenal axis (HPA) dysregulation, can exacerbate both. However, little is known about the factors that predispose individuals to the development of both anxiety disorders and nicotine use. Here, we examined the relationship between anxiety-like behaviors and nicotine responses following adolescent stress. Adolescent male and female BALB/cJ mice were exposed to either chronic variable social stress (CVSS) or control conditions. CVSS consisted of repeated cycles of social isolation and social reorganization. In adulthood, anxiety-like behavior and social avoidance were measured using the elevated plus-maze (EPM) and social approach-avoidance test, respectively. Nicotine responses were assessed with acute effects on body temperature, corticosterone production, locomotor activity, and voluntary oral nicotine consumption. Adolescent stress had sex-dependent effects on nicotine responses and exploratory behavior, but did not affect anxiety-like behavior or social avoidance in males or females. Adult CVSS males exhibited less exploratory behavior, as indicated by reduced exploratory locomotion in the EPM and social approach-avoidance test, compared to controls. Adolescent stress did not affect nicotine-induced hypothermia in either sex, but CVSS males exhibited augmented nicotine-induced locomotion during late adolescence and voluntarily consumed less nicotine during adulthood. Stress effects on male nicotine-induced locomotion were associated with individual differences in exploratory locomotion in the EPM and social approach-avoidance test. Relative to controls, adult CVSS males and females also exhibited reduced corticosterone levels at baseline and adult male CVSS mice exhibited increased corticosterone levels following an acute nicotine injection. Results

  4. Antidepressant-like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with fluoxetine [correction of flouxetine].

    Science.gov (United States)

    Vázquez-Palacios, G; Bonilla-Jaime, H; Velázquez-Moctezuma, J

    2004-05-01

    An antidepressant action of nicotine (NIC) has recently been suggested. Flouxetine, a selective serotonin reuptake inhibitor, is currently the most widely used antidepressant. In the present study, we analyzed the effects of the administration of NIC, fluoxetine (FLX), and the combination of both drugs given acutely, subchronically, and chronically as well as 7 days after chronic administration of these drugs on the forced swim test. Results showed that NIC induced a significant reduction of the time in immobility during the forced swim test (antidepressant effect), with a concomitant increase in swimming activity (serotonergic activation), after acute administration. These effects remain the same after subchronic and chronic administration. FLX failed to induce any effect after acute administration but did induce a significant decrease of immobility and an increase of swimming after subchronic administration. The effect of the chronic administration was significantly larger compared to subchronic administration. The combination of both drugs induced a larger effect than that observed after a single administration but only after subchronic treatment. No effect was observed after the end of the 7-day treatments. Data suggest that NIC has an antidepressant action that is expressed faster than FLX but remains the same later. Thus, cholinergic-serotonergic interactions could play an important role in the treatment of depression.

  5. Effects of nicotine on visuo-spatial selective attention as indexed by event-related potentials.

    Science.gov (United States)

    Meinke, A; Thiel, C M; Fink, G R

    2006-08-11

    Nicotine has been shown to specifically reduce reaction times to invalidly cued targets in spatial cueing paradigms. In two experiments, we used event-related potentials to test whether the facilitative effect of nicotine upon the detection of invalidly cued targets is due to a modulation of perceptual processing, as indexed by early attention-related event-related potential components. Furthermore, we assessed whether the effect of nicotine on such unattended stimuli depends upon the use of exogenous or endogenous cues. In both experiments, the electroencephalogram was recorded while non-smokers completed discrimination tasks in Posner-type paradigms after chewing a nicotine polacrilex gum (Nicorette 2 mg) in one session and a placebo gum in another session. Nicotine reduced reaction times to invalidly cued targets when cueing was endogenous. In contrast, no differential effect of nicotine on reaction times was observed when exogenous cues were used. Electrophysiologically, we found a similar attentional modulation of the P1 and N1 components under placebo and nicotine but a differential modulation of later event-related potential components at a frontocentral site. The lack of a drug-dependent modulation of P1 and N1 in the presence of a behavioral effect suggests that the effect of nicotine in endogenous visuo-spatial cueing tasks is not due to an alteration of perceptual processes. Rather, the differential modulation of frontocentral event-related potentials suggests that nicotine acts at later stages of target processing.

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

    Science.gov (United States)

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

    2015-10-01

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

  7. 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.

  8. [Safety and effectiveness of nicotinic acid in the management of patients with chronic renal disease and hyperlipidemia associated to hyperphosphatemia].

    Science.gov (United States)

    Restrepo Valencia, C A; Cruz, J

    2008-01-01

    To establish if the nicotinic acid in patients with chronic renal disease reduce significantly and with security the levels of lipids and serum phosphate in refractory patients to the classical management. Observational study Place: Renal Unity RTS Ltda Caldas Santa Sofìa Hospital. All the patients with chronic renal disease in dialysis therapy to whom the classical treatment for their hyperlipidaemia and hyperphosphatemia didn't manage a satisfactory reduce of their serum levels. It was identified that those patients who in the 3 previous months to the intervention hadn't presented changes in the lipids profile even though they received low fats diet and a lipid lowering therapies (statin o fibric acid derivates). It was determined in them whether they presented levels of serum phosphorus greater than 5.5 mg/dl even though having received nutritional recommendations and treatment with oral phosphate binding agents (Aluminum hydroxide, Calcium salts or Sevelamer). In them it was proceeded to administrate nicotinic acid via oral at night until a doses of 1,000 milligrams was reached (preceded of 100 mgs of acetylsalicylic acid 1 hour before) during a period of 8 months, observing its therapeutical effectivity and security profile to improve the lipids profile and reduce the serum phosphorus. 9 patients complied with the requirements, average time in dialysis 34 months, 3 in hemodialysis and 6 in peritoneal dialysis. All patients started with 500 mgs and 3 months later correctly tolerated the dose of 1,000 mgs. Between the evaluated variables, the most important changes were: the phosphorus reduced reaching a significant value at eight months: initial 6.46+/-0.53, four months 4.37+/-0.63 (p>0.05) and eight months 3.94+/-0.76 (padherence to the medicament 100%. The nicotinic acid is efficient, very well tolerated and economical in comparison with others drugs, which makes it ideal for the treatment of patients with hyperlipidaemia and refractory hyperphosphatemia to

  9. Chronic Underactivity of Medial Frontal Cortical β2-Containing Nicotinic Receptors Increases Clozapine-Induced Working Memory Impairment in Female Rats

    Science.gov (United States)

    Levin, Edward D.; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N. Channelle

    2009-01-01

    Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of β2-containing nicotinic receptors with dihydro-β-erythrodine (DHβE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal α7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical α7 and β2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHβE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHβE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHβE infusion potentiated clozapine-induced memory impairment, whereas previously the memory

  10. Chronic underactivity of medial frontal cortical beta2-containing nicotinic receptors increases clozapine-induced working memory impairment in female rats.

    Science.gov (United States)

    Levin, Edward D; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N Channelle

    2009-03-17

    Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of beta2-containing nicotinic receptors with dihydro-beta-erythrodine (DHbetaE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal alpha7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical alpha7 and beta2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHbetaE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHbetaE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHbetaE infusion potentiated clozapine-induced memory impairment, whereas previously

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

    Science.gov (United States)

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

    2015-01-01

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

  12. alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity.

    Science.gov (United States)

    de Fiebre, Nancyellen C; de Fiebre, Christopher M

    2005-01-03

    The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been implicated as a potential site of action for two neurotoxins, ethanol and the Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to examine the role of this receptor in modulating the neurotoxic properties of subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however, was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha-bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7 nAChRs modulate the neurotoxic effects of binge ethanol, but not the neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of alpha7 nAChRs by ethanol provides partial protection against the neurotoxic properties of subchronic ethanol.

  13. 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.

  14. Selective decreases of nicotinic acetylcholine receptors in PC12 cells exposed to fluoride

    International Nuclear Information System (INIS)

    Chen Jia; Shan, K.-R.; Long, Y.-G.; Wang, Y.-N.; Nordberg, Agneta; Guan, Z.-Z.

    2003-01-01

    In an attempt to elucidate the mechanism by which excessive fluoride damages the central nervous system, the effects of exposure of PC12 cells to different concentrations of fluoride for 48 h on nicotinic acetylcholine receptors (nAChRs) were characterized here. Significant reductions in the number of binding sites for both [ 3 H]epibatidine and [ 125 I]α-bungarotoxin, as well as a significant decrease in the B max value for the high-affinity of epibatidine binding site were observed in PC12 cells subjected to high levels of fluoride. On the protein level, the α3 and α7 subunits of nAChRs were also significantly decreased in the cells exposed to high concentrations of fluoride. In contrast, such exposure had no significant effect on the level of the β2 subunit. These findings suggest that selective decreases in the number of nAChRs may play an important role in the mechanism(s) by which fluoride causes dysfunction of the central nervous system

  15. Selected constituents in the smokes of foreign commercial cigaretts: tar, nicotine, carbon monoxide, and carbon dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins, R.A.; Quincy, R.B.; Guerin, M.R.

    1979-05-01

    The tar, nicotine, carbon monoxide, and carbon dioxide contents of the smokes of 220 brands of foreign commercial cigarettes are reported. In some instances, filter cigarettes of certain brands were found to deliver as much or more smoke constituents than their nonfilter counterparts. Also, data indicated that there can be a great variation in the tar, nicotine, or carbon monoxide content of the smoke of samples of a given brand of cigarettes, depending on the nation in which they are purchased. 24 tables.

  16. The association between nicotine dependence and physical health among people receiving injectable diacetylmorphine or hydromorphone for the treatment of chronic opioid use disorder

    Directory of Open Access Journals (Sweden)

    Heather Palis

    2018-06-01

    Full Text Available Introduction: People with chronic opioid use disorder often present to treatment with individual and structural vulnerabilities and remain at risk of reporting adverse health outcomes. This risk is greatly compounded by tobacco smoking, which is highly prevalent among people with chronic opioid use disorder. Despite the known burden of tobacco smoking on health, the relationship between nicotine dependence and health has not been studied among those receiving injectable opioid agonist treatment. As such, the present study aims to explore the association between nicotine dependence and physical health among participants of the Study to Assess Longer-Term Opioid Medication Effectiveness (SALOME at baseline and six-months. Methods: SALOME was a double-blind phase III clinical trial testing the non-inferiority of injectable hydromorphone to injectable diacetylmorphine for chronic opioid use disorder. Participants reporting tobacco smoking were included in a linear regression analysis of physical health at baseline (before receiving treatment and at six-months. Results: At baseline, nicotine dependence score, lifetime history of emotional, physical, or sexual abuse and prior month safe injection site access were independently and significantly associated with physical health. At six-months nicotine dependence score was the only variable that maintained this significant and independent association with physical health. Conclusions: Findings indicate that after six-months, the injectable treatment effectively brought equity to patients' physical health status, yet the association with nicotine dependence remained. Findings could inform whether the provision of treatment for nicotine dependence should be made a priority in settings where injectable opioid agonist treatment is delivered to achieve improvements in overall physical health in this population.

  17. 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

  18. 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 ...

  19. 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.

  20. The α4β2 nicotine acetylcholine receptor agonist ispronicline induces c-Fos expression in selective regions of the rat forebrain

    DEFF Research Database (Denmark)

    Jacobsen, Julie; Hansen, Henrik H; Kiss, Alexander

    2012-01-01

    The dominant nicotine acetylcholine receptor (nAChR) subtype in the brain is the pentameric receptor containing both α4 and β2 subunits (α4β2). Due to the lack of selective agonists it has not been ruled out what neuronal circuits that are stimulated after systemic administration with nicotine. We...... or indirectly involved in acute stress regulation after a single dose of ispronicline, supports earlier studies that the α4β2 receptors are strongly involved in nicotine-dependent activation of the hypothalamo-pituitary adrenocortical axis....

  1. 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.

  2. Chronic Nicotine Exposure Initiated in Adolescence and Unpaired to Behavioral Context Fails to Enhance Sweetened Ethanol Seeking

    Directory of Open Access Journals (Sweden)

    Aric C. Madayag

    2017-08-01

    Full Text Available Nicotine use in adolescence is pervasive in the United States and, according to the Gateway Hypothesis, may lead to progression towards other addictive substances. Given the prevalence of nicotine and ethanol comorbidity, it is difficult to ascertain if nicotine is a gateway drug for ethanol. Our study investigated the relationship between adolescent exposure to nicotine and whether this exposure alters subsequent alcohol seeking behavior. We hypothesized that rats exposed to nicotine beginning in adolescence would exhibit greater alcohol seeking behavior than non-exposed siblings. To test our hypothesis, beginning at P28, female rats were initially exposed to once daily nicotine (0.4 mg/kg, SC or saline for 5 days. Following these five initial injections, animals were trained to nose-poke for sucrose reinforcement (10%, w/v, gradually increasing to sweetened ethanol (10% sucrose; 10% ethanol, w/v on an FR5 reinforcement schedule. Nicotine injections were administered after the behavioral sessions to minimize acute effects of nicotine on operant self-administration. We measured the effects of nicotine exposure on the following aspects of ethanol seeking: self-administration, naltrexone (NTX-induced decreases, habit-directed behavior, motivation, extinction and reinstatement. Nicotine exposure did not alter self-administration or the effectiveness of NTX to reduce alcohol seeking. Nicotine exposure blocked habit-directed ethanol seeking. Finally, nicotine did not alter extinction learning or cue-induced reinstatement to sweetened ethanol seeking. Our findings suggest that nicotine exposure outside the behavioral context does not escalate ethanol seeking. Further, the Gateway Hypothesis likely applies to scenarios in which nicotine is either self-administered or physiologically active during the behavioral session.

  3. Azemiopsin, a Selective Peptide Antagonist of Muscle Nicotinic Acetylcholine Receptor: Preclinical Evaluation as a Local Muscle Relaxant

    Directory of Open Access Journals (Sweden)

    Irina V. Shelukhina

    2018-01-01

    Full Text Available Azemiopsin (Az, a linear peptide from the Azemiops feae viper venom, contains no disulfide bonds, is a high-affinity and selective inhibitor of nicotinic acetylcholine receptor (nAChR of muscle type and may be considered as potentially applicable nondepolarizing muscle relaxant. In this study, we investigated its preclinical profile in regard to in vitro and in vivo efficacy, acute and chronic toxicity, pharmacokinetics, allergenic capacity, immunotoxicity and mutagenic potency. The peptide effectively inhibited (IC50 ~ 19 nM calcium response of muscle nAChR evoked by 30 μM (EC100 acetylcholine but was less potent (IC50 ~ 3 μM at α7 nAChR activated by 10 μM (EC50 acetylcholine and had a low affinity to α4β2 and α3-containing nAChR, as well as to GABAA or 5HT3 receptors. Its muscle relaxant effect was demonstrated at intramuscular injection to mice at doses of 30–300 µg/kg, 30 µg/kg being the initial effective dose and 90 µg/kg—the average effective dose. The maximal muscle relaxant effect of Az was achieved in 10 min after the administration and elimination half-life of Az in mice was calculated as 20–40 min. The longest period of Az action observed at a dose of 300 µg/kg was 55 min. The highest acute toxicity (LD50 510 μg/kg was observed at intravenous injection of Az, at intramuscular or intraperitoneal administration it was less toxic. The peptide showed practically no immunotoxic, allergenic or mutagenic capacity. Overall, the results demonstrate that Az has good drug-like properties for the application as local muscle relaxant and in its parameters, is not inferior to the relaxants currently used. However, some Az modification might be effective to extend its narrow therapeutic window, a typical characteristic and a weak point of all nondepolarizing myorelaxants.

  4. Differential Regulation of Receptor Activation and Agonist Selectivity by Highly Conserved Tryptophans in the Nicotinic Acetylcholine Receptor Binding Site

    OpenAIRE

    Williams, Dustin K.; Stokes, Clare; Horenstein, Nicole A.; Papke, Roger L.

    2009-01-01

    We have shown previously that a highly conserved Tyr in the nicotinic acetylcholine receptor (nAChR) ligand-binding domain (LBD) (α7 Tyr188 or α4 Tyr195) differentially regulates the activity of acetylcholine (ACh) and the α7-selective agonist 3-(4-hydroxy,2-methoxybenzylidene)anabaseine (4OH-GTS-21) in α4β2 and α7 nAChR. In this study, we mutated two highly conserved LBD Trp residues in human α7 and α4β2 and expressed the receptors in Xenopus laevis oocytes. α7 Re...

  5. Withdrawal from chronic exposure to amphetamine, but not nicotine, leads to an immediate and enduring deficit in motivated behavior without affecting social interaction in rats.

    Science.gov (United States)

    Der-Avakian, Andre; Markou, Athina

    2010-07-01

    Psychostimulant withdrawal leads to depressive symptoms, such as anhedonia and social dysfunction. We determined the effects of withdrawal from chronic exposure to nicotine (9 mg/kg/day salt, 28 days) or amphetamine (10 mg/kg/day salt, 7 days) on the motivated response for a sucrose reward and on social interaction in rats. Both nicotine and amphetamine exposure increased the motivated response for sucrose. However, only spontaneous amphetamine withdrawal led to an immediate and persistent decrease in motivated behavior, which was not correlated with body weight loss. Social interaction was not affected during withdrawal from either drug. These results indicate that withdrawal from chronic amphetamine exposure leads to an immediate and enduring anhedonic state.

  6. Regulation of nicotinic receptor subtypes following chronic nicotinic agonist exposure in M10 and SH-SY5Y neuroblastoma cells

    DEFF Research Database (Denmark)

    Warpman, U; Friberg, L; Gillespie, A

    1998-01-01

    investigated in human neuroblastoma SH-SY5Y cells (expressing alpha3, alpha5, beta2, and beta4 nAChR subunits). Nicotine exhibited a 14 times lower affinity for the nAChRs in SH-SY5Y cells as compared with M10 cells, whereas epibatidine showed similar affinities for the nAChRs expressed in the two cell lines...

  7. EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Prickaerts, Jos; van Goethem, Nick P; Chesworth, Richard; Shapiro, Gideon; Boess, Frank G; Methfessel, Christoph; Reneerkens, Olga A H; Flood, Dorothy G; Hilt, Dana; Gawryl, Maria; Bertrand, Sonia; Bertrand, Daniel; König, Gerhard

    2012-02-01

    EVP-6124, (R)-7-chloro-N-quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide, is a novel partial agonist of α7 neuronal nicotinic acetylcholine receptors (nAChRs) that was evaluated here in vitro and in vivo. In binding and functional experiments, EVP-6124 showed selectivity for α7 nAChRs and did not activate or inhibit heteromeric α4β2 nAChRs. EVP-6124 had good brain penetration and an adequate exposure time. EVP-6124 (0.3 mg/kg, p.o.) significantly restored memory function in scopolamine-treated rats (0.1 mg/kg, i.p.) in an object recognition task (ORT). Although donepezil at 0.1 mg/kg, p.o. or EVP-6124 at 0.03 mg/kg, p.o. did not improve memory in this task, co-administration of these sub-efficacious doses fully restored memory. In a natural forgetting test, an ORT with a 24 h retention time, EVP-6124 improved memory at 0.3 mg/kg, p.o. This improvement was blocked by the selective α7 nAChR antagonist methyllycaconitine (0.3 mg/kg, i.p. or 10 μg, i.c.v.). In co-application experiments of EVP-6124 with acetylcholine, sustained exposure to EVP-6124 in functional investigations in oocytes caused desensitization at concentrations greater than 3 nM, while lower concentrations (0.3-1 nM) caused an increase in the acetylcholine-evoked response. These actions were interpreted as representing a co-agonist activity of EVP-6124 with acetylcholine on α7 nAChRs. The concentrations of EVP-6124 that resulted in physiological potentiation were consistent with the free drug concentrations in brain that improved memory performance in the ORT. These data suggest that the selective partial agonist EVP-6124 improves memory performance by potentiating the acetylcholine response of α7 nAChRs and support new therapeutic strategies for the treatment of cognitive impairment. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Differential Modulation of GABAA and NMDA Receptors by an α7-nicotinic Acetylcholine Receptor Agonist in Chronic Glaucoma

    Directory of Open Access Journals (Sweden)

    Xujiao Zhou

    2017-12-01

    Full Text Available Presynaptic modulation of γ-aminobutyric acid (GABA release by an alpha7 nicotinic acetylcholine receptor (α7-nAChR agonist promotes retinal ganglion cell (RGC survival and function, as suggested by a previous study on a chronic glaucomatous model from our laboratory. However, the role of excitatory and inhibitory amino acid receptors and their interaction with α7-nAChR in physiological and glaucomatous events remains unknown. In this study, we investigated GABAA and N-methyl-D-aspartate (NMDA receptor activity in control and glaucomatous retinal slices and the regulation of amino acid receptor expression and function by α7-nAChR. Whole-cell patch-clamp recordings from RGCs revealed that the α7-nAChR specific agonist PNU-282987 enhanced the amplitude of currents elicited by GABA and reduced the amplitude of currents elicited by NMDA. The positive modulation of GABAA receptor and the negative modulation of NMDA receptor (NMDAR by PNU-282987-evoked were prevented by pre-administration of the α7-nAChR antagonist methyllycaconitine (MLA. The frequency and the amplitude of glutamate receptor-mediated miniature glutamatergic excitatory postsynaptic currents (mEPSCs were not significantly different between the control and glaucomatous RGCs. Additionally, PNU-282987-treated slices showed no alteration in the frequency or amplitude of mEPSCs relative to control RGCs. Moreover, we showed that expression of the α1 subunit of the GABAA receptor was downregulated and the expression of the NMDAR NR2B subunit was upregulated by intraocular pressure (IOP elevation, and the changes of high IOP were blocked by PNU-282987. In conclusion, retina GABAA and NMDARs are modulated positively and negatively, respectively, by activation of α7-nAChR in in vivo chronic glaucomatous models.

  9. The alpha7 nicotinic acetylcholine receptor-selective antagonist, methyllycaconitine, partially protects against beta-amyloid1-42 toxicity in primary neuron-enriched cultures.

    Science.gov (United States)

    Martin, Shelley E; de Fiebre, Nancy Ellen C; de Fiebre, Christopher M

    2004-10-01

    Studies have suggested that the neuroprotective actions of alpha7 nicotinic agonists arise from activation of receptors and not from the extensive desensitization which rapidly follows activation. Here, we report that the alpha7-selective nicotinic antagonist, methyllycaconitine (MLA), protects against beta-amyloid-induced neurotoxicity; whereas the alpha4beta2-selective antagonist, dihydro-beta-erythroidine, does not. These findings suggest that neuroprotective actions of alpha7-acting agents arise from receptor inhibition/desensitization and that alpha7 antagonists may be useful neuroprotective agents.

  10. Selective Attention to Visual Stimuli Using Auditory Distractors Is Altered in Alpha-9 Nicotinic Receptor Subunit Knock-Out Mice.

    Science.gov (United States)

    Terreros, Gonzalo; Jorratt, Pascal; Aedo, Cristian; Elgoyhen, Ana Belén; Delano, Paul H

    2016-07-06

    During selective attention, subjects voluntarily focus their cognitive resources on a specific stimulus while ignoring others. Top-down filtering of peripheral sensory responses by higher structures of the brain has been proposed as one of the mechanisms responsible for selective attention. A prerequisite to accomplish top-down modulation of the activity of peripheral structures is the presence of corticofugal pathways. The mammalian auditory efferent system is a unique neural network that originates in the auditory cortex and projects to the cochlear receptor through the olivocochlear bundle, and it has been proposed to function as a top-down filter of peripheral auditory responses during attention to cross-modal stimuli. However, to date, there is no conclusive evidence of the involvement of olivocochlear neurons in selective attention paradigms. Here, we trained wild-type and α-9 nicotinic receptor subunit knock-out (KO) mice, which lack cholinergic transmission between medial olivocochlear neurons and outer hair cells, in a two-choice visual discrimination task and studied the behavioral consequences of adding different types of auditory distractors. In addition, we evaluated the effects of contralateral noise on auditory nerve responses as a measure of the individual strength of the olivocochlear reflex. We demonstrate that KO mice have a reduced olivocochlear reflex strength and perform poorly in a visual selective attention paradigm. These results confirm that an intact medial olivocochlear transmission aids in ignoring auditory distraction during selective attention to visual stimuli. The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through the olivocochlear system. It has been proposed to function as a top-down filter of peripheral auditory responses during attention to cross-modal stimuli. However, to date, there is no conclusive evidence of the involvement of olivocochlear

  11. Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian R; Andersen, Kim

    2002-01-01

    Philanthotoxin-12 (PhTX-12) is a novel potent and selective, noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Homologues of PhTX-12 with 7-11 methylene groups between the primary amino group and the aromatic head-group were synthesized using solid-phase methodology. In vitro...

  12. Human Secreted Ly-6/uPAR Related Protein-1 (SLURP-1) Is a Selective Allosteric Antagonist of α7 Nicotinic Acetylcholine Receptor

    DEFF Research Database (Denmark)

    Lyukmanova, Ekaterina N; Shulepko, Mikhail A; Kudryavtsev, Denis

    2016-01-01

    of nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors, respectively, and anti-α7-nAChRs antibodies revealed α7 type nAChRs as an rSLURP-1 target in keratinocytes. Using affinity purification from human cortical extracts, we confirmed that rSLURP-1 binds selectively to the α7-n...

  13. Alpha-conotoxin analogs with additional positive charge show increased selectivity towards Torpedo californica and some neuronal subtypes of nicotinic acetylcholine receptors

    NARCIS (Netherlands)

    Kasheverov, I.E.; Zhmak, M.N.; Vulfius, C.A.; Corbacheva, E.V.; Mordvintsev, D.Y.; Utkin, Y.N.; van Elk, R.; Smit, A.B.; Tsetlin, V.I.

    2006-01-01

    α-Conotoxins from Conus snails are indispensable tools for distinguishing various subtypes of nicotinic acetylcholine receptors (nAChRs), and synthesis of α-conotoxin analogs may yield novel antagonists of higher potency and selectivity. We incorporated additional positive charges into α-conotoxins

  14. Secondhand tobacco smoke exposure in selected public places (PM2.5 and air nicotine) and non-smoking employees (hair nicotine) in Ghana.

    Science.gov (United States)

    Agbenyikey, Wilfred; Wellington, Edith; Gyapong, John; Travers, Mark J; Breysse, Patrick N; McCarty, Kathleen M; Navas-Acien, Ana

    2011-03-01

    Secondhand tobacco smoke (SHS) exposure is a global public health problem. Ghana currently has no legislation to prevent smoking in public places. To provide data on SHS levels in hospitality venues in Ghana the authors measured (1) airborne particulate matter working in smoking venues (median 2.49 [0.46-6.84] ng/mg) compared to those working in non-smoking venues (median 0.16 [0.08-0.79]ng/mg). Hair nicotine concentrations correlated with self-reported hours of SHS exposure (r=0.35), indoor air PM(2.5) concentrations (r=0.47) and air nicotine concentrations (r=0.63). SHS levels were unacceptably high in public places in Ghana where smoking is allowed, despite a relatively low-smoking prevalence in the country. This is one of the first studies to ascertain SHS and hair nicotine in Africa. Levels were comparable to those measured in American, Asian and European countries without or before smoking bans. Implementing a comprehensive smoke-free legislation that protects workers and customers from exposure to secondhand smoke is urgently needed in Ghana.

  15. Selection of a novel anti-nicotine vaccine: influence of antigen design on antibody function in mice.

    Directory of Open Access Journals (Sweden)

    David C Pryde

    Full Text Available Anti-nicotine vaccines may aid smoking cessation via the induction of anti-nicotine antibodies (Ab which reduce nicotine entering the brain, and hence the associated reward. Ab function depends on both the quantity (titer and the quality (affinity of the Ab. Anti-nicotine vaccines tested previously in clinical studies had poor efficacy despite high Ab titer, and this may be due to inadequate function if Ab of low affinity were induced. In this study, we designed and synthesized a series of novel nicotine-like haptens which were all linked to diphtheria toxoid (DT as carrier, but which differed in the site of attachment of linker to nicotine, the nature of linker used, and the handle used to attach the hapten to DT. The resulting hapten conjugates were evaluated in a mouse model, using CpG (a TLR9 agonist and aluminum hydroxide (Al(OH3 as adjuvants, whereby Ab titers, affinity and function were evaluated using a radiolabeled nicotine challenge model. A series of additional linkers varying in length, rigidity and polarity were used with a single hapten to generate additional DT-conjugates, which were also tested in mice. Conjugates made with different haptens resulted in various titers of anti-nicotine Ab. Several haptens gave similarly high Ab titers, but among these, Ab affinity and hence function varied considerably. Linker also influenced Ab titer, affinity and function. These results demonstrate that immune responses induced in mice by nicotine-conjugate antigens are greatly influenced by hapten design including site of attachment of linker to nicotine, the nature of linker used, and the handle used to attach the hapten to DT. While both Ab titer and affinity contributed to function, affinity was more sensitive to antigen differences.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

  18. Glutamine 57 at the complementary binding site face is a key determinant of morantel selectivity for {alpha}7 nicotinic receptors.

    Science.gov (United States)

    Bartos, Mariana; Price, Kerry L; Lummis, Sarah C R; Bouzat, Cecilia

    2009-08-07

    Nicotinic receptors (AChRs) play key roles in synaptic transmission. We explored activation of neuronal alpha7 and mammalian muscle AChRs by morantel and oxantel. Our results revealed a novel action of morantel as a high efficacy and more potent agonist than ACh of alpha7 receptors. The EC(50) for activation by morantel of both alpha7 and alpha7-5HT(3A) receptors is 7-fold lower than that determined for ACh. The minimum morantel concentration required to activate alpha7-5HT(3A) channels is 6-fold lower than that of ACh, and activation episodes are more prolonged than in the presence of ACh. By contrast, oxantel is a weak agonist of alpha7 and alpha7-5HT(3A), and both drugs are very low efficacy agonists of muscle AChRs. The replacement of Gln(57) in alpha7 by glycine, which is found in the equivalent position of the muscle AChR, decreases the efficacy for activation and turns morantel into a partial agonist. The reverse mutation in the muscle AChR (epsilonG57Q) increases 7-fold the efficacy of morantel. The mutations do not affect activation by ACh or oxantel, indicating that this position is selective for morantel. In silico studies show that the tetrahydropyrimidinyl group, common to both drugs, is close to Trp(149) of the principal face of the binding site, whereas the other cyclic group is proximal to Gln(57) of the complementary face in morantel but not in oxantel. Thus, position 57 at the complementary face is a key determinant of the high selectivity of morantel for alpha7. These results provide new information for further progress in drug design.

  19. Phenotypes selected during chronic lung infection in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang

    2012-01-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by g...... the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis....

  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. In vitro pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107.

    Science.gov (United States)

    Malysz, John; Anderson, David J; Grønlien, Jens H; Ji, Jianguo; Bunnelle, William H; Håkerud, Monika; Thorin-Hagene, Kirten; Ween, Hilde; Helfrich, Rosalind; Hu, Min; Gubbins, Earl; Gopalakrishnan, Sujatha; Puttfarcken, Pamela S; Briggs, Clark A; Li, Jinhe; Meyer, Michael D; Dyhring, Tino; Ahring, Philip K; Nielsen, Elsebet Ø; Peters, Dan; Timmermann, Daniel B; Gopalakrishnan, Murali

    2010-09-01

    Enhancement of alpha7 nicotinic acetylcholine receptor (nAChR) activity is considered a therapeutic approach for ameliorating cognitive deficits present in Alzheimer's disease and schizophrenia. In this study, we describe the in vitro profile of a novel selective alpha7 nAChR agonist, 5-(6-[(3R)-1-azabicyclo[2,2,2]oct-3-yloxy]pyridazin-3-yl)-1H-indole (ABT-107). ABT-107 displayed high affinity binding to alpha7 nAChRs [rat or human cortex, [(3)H](1S,4S)-2,2-dimethyl-5-(6-phenylpyridazin-3-yl)-5-aza-2-azoniabicyclo[2.2.1]heptane (A-585539), K(i) = 0.2-0.6 nM or [(3)H]methyllycaconitine (MLA), 7 nM] that was at least 100-fold selective versus non-alpha7 nAChRs and other receptors. Functionally, ABT-107 did not evoke detectible currents in Xenopus oocytes expressing human or nonhuman alpha3beta4, chimeric (alpha6/alpha3)beta4, or 5-HT(3A) receptors, and weak or negligible Ca(2+) responses in human neuroblastoma IMR-32 cells (alpha3* function) and human alpha4beta2 and alpha4beta4 nAChRs expressed in human embryonic kidney 293 cells. ABT-107 potently evoked human and rat alpha7 nAChR current responses in oocytes (EC(50), 50-90 nM total charge, approximately 80% normalized to acetylcholine) that were enhanced by the positive allosteric modulator (PAM) 4-[5-(4-chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]-benzenesulfonamide (A-867744). In rat hippocampus, ABT-107 alone evoked alpha7-like currents, which were inhibited by the alpha7 antagonist MLA. In dentate gyrus granule cells, ABT-107 enhanced spontaneous inhibitory postsynaptic current activity when coapplied with A-867744. In the presence of an alpha7 PAM [A-867744 or N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-120596)], the addition of ABT-107 elicited MLA-sensitive alpha7 nAChR-mediated Ca(2+) signals in IMR-32 cells and rat cortical cultures and enhanced extracellular signal-regulated kinase phosphorylation in differentiated PC-12 cells. ABT-107 was also effective in protecting rat

  2. Selected constituents in the smokes of U. S. commercial cigaretts: tar, nicotine, carbon monoxide and carbon dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins, R.A.; Quincy, R.B.; Guerin, M.R.

    1979-05-01

    One hundred twenty-one brands of United States commercial cigarettes were analyzed for their deliveries of tar, nicotine, carbon monoxide, and carbon dioxide under standard analytical smoking conditions. The sample included both filter and nonfilter cigarettes. Comparisons of carbon monoxide deliveries over the range of observed tar deliveries indicated a very high correlation between CO and tar for filter cigarettes, but nonfilter cigarettes tended to produce much less CO than would have been predicted from their tar deliveries. Comparison of ORNL nicotine values for specific brands with those determined by the Federal Trade Commission yield no statistically significant differences between laboratories. 4 figures, 6 tables.

  3. 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.

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

    Science.gov (United States)

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

    2017-04-01

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

  5. Activation and desensitization of peripheral muscle and neuronal nicotinic acetylcholine receptors by selected, naturally-occurring pyridine alkaloids

    Science.gov (United States)

    Teratogenic alkaloids can cause developmental defects due to inhibition of fetal movement that results from desensitization of fetal muscletype nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiper...

  6. 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.

  7. Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?

    Science.gov (United States)

    Sacchi, Oscar; Rossi, Maria Lisa; Canella, Rita; Fesce, Riccardo

    2011-02-25

    The permeability of the nicotinic channel (nAChR) at the ganglionic synapse has been examined, in the intact rat superior cervical ganglion in vitro, by fitting the Goldman current equation to the synaptic current (EPSC) I-V relationship. Subsynaptic nAChRs, activated by neurally-released acetylcholine (ACh), were thus analyzed in an intact environment as natively expressed by the mature sympathetic neuron. Postsynaptic neuron hyperpolarization (from -40 to -90 mV) resulted in a change of the synaptic potassium/sodium permeability ratio (P(K)/P(Na)) from 1.40 to 0.92, corresponding to a reversible shift of the apparent acetylcholine equilibrium potential, E(ACh), by about +10 mV. The effect was accompanied by a decrease of the peak synaptic conductance (g(syn)) and of the EPSC decay time constant. Reduction of [Cl(-)](o) to 18 mM resulted in a change of P(K)/P(Na) from 1.57 (control) to 2.26, associated with a reversible shift of E(ACh) by about -10 mV. Application of 200 nM αBgTx evoked P(K)/P(Na) and g(syn) modifications similar to those observed in reduced [Cl(-)](o). The two treatments were overlapping and complementary, as if the same site/mechanism were involved. The difference current before and after chloride reduction or toxin application exhibited a strongly positive equilibrium potential, which could not be explained by the block of a calcium component of the EPSC. Observations under current-clamp conditions suggest that the driving force modification of the EPSC due to P(K)/P(Na) changes represent an additional powerful integrative mechanism of neuron behavior. A possible role for chloride ions is suggested: the nAChR selectivity was actually reduced by increased chloride gradient (membrane hyperpolarization), while it was increased, moving towards a channel preferentially permeable for potassium, when the chloride gradient was reduced.

  8. Changes in cationic selectivity of the nicotinic channel at the rat ganglionic synapse: a role for chloride ions?

    Directory of Open Access Journals (Sweden)

    Oscar Sacchi

    Full Text Available The permeability of the nicotinic channel (nAChR at the ganglionic synapse has been examined, in the intact rat superior cervical ganglion in vitro, by fitting the Goldman current equation to the synaptic current (EPSC I-V relationship. Subsynaptic nAChRs, activated by neurally-released acetylcholine (ACh, were thus analyzed in an intact environment as natively expressed by the mature sympathetic neuron. Postsynaptic neuron hyperpolarization (from -40 to -90 mV resulted in a change of the synaptic potassium/sodium permeability ratio (P(K/P(Na from 1.40 to 0.92, corresponding to a reversible shift of the apparent acetylcholine equilibrium potential, E(ACh, by about +10 mV. The effect was accompanied by a decrease of the peak synaptic conductance (g(syn and of the EPSC decay time constant. Reduction of [Cl(-](o to 18 mM resulted in a change of P(K/P(Na from 1.57 (control to 2.26, associated with a reversible shift of E(ACh by about -10 mV. Application of 200 nM αBgTx evoked P(K/P(Na and g(syn modifications similar to those observed in reduced [Cl(-](o. The two treatments were overlapping and complementary, as if the same site/mechanism were involved. The difference current before and after chloride reduction or toxin application exhibited a strongly positive equilibrium potential, which could not be explained by the block of a calcium component of the EPSC. Observations under current-clamp conditions suggest that the driving force modification of the EPSC due to P(K/P(Na changes represent an additional powerful integrative mechanism of neuron behavior. A possible role for chloride ions is suggested: the nAChR selectivity was actually reduced by increased chloride gradient (membrane hyperpolarization, while it was increased, moving towards a channel preferentially permeable for potassium, when the chloride gradient was reduced.

  9. Metals and Nicotine Level in Preparations of Rubisco Purified from Cuban Tobacco Varieties, for Chronic Renal Insufficiency Patients

    International Nuclear Information System (INIS)

    Geada, D.; Ares, D.; Del Castillo, N.; Valdes, R.; Gonzalez, M.; Rodriguez, D.; Ferro, W.; Gomez, L.; Padilla, S.; Roman, M. R.; Hidalgo, A.; Zamora, A.

    2003-01-01

    Full Text: Foods are the major source of metals accumulation in the humans. Plants contain large quantities of Rubisco to attain reasonable rates of photosynthesis, and thus, is the most abundant protein on Earth. Rubisco could be used as additive in nutrition for people with renal insufficiency, comatose state and severely restrict Na and K because the absence of these metals can greatly reduce the frequency of haemodialysis. Our purpose was to measure the metal levels and estimate the potential intake of copper, iron, zinc and manganese in patients under haemodialysis treatment and coma. Additionally we also studied sodium, potassium, calcium and magnesium quantities. Intakes of these metals were estimated, attending to the quantity of protein by person, from their daily diets and compared with the Provisional Tolerable Weekly Intakes (PTWI) as established by the FAO/WHO and the US Recommended Daily Allowances (RDA) or the US Safe and Adequate Daily Dietary Intakes (ESADDI). All the determinations of these metals were done using atomic absorption spectrometry and none of them exceeds PTWI, RDA and ESADDI values; nevertheless they were higher than the values previously obtained. The highest metal value, respect the daily allowances, was obtained for iron. Lowest values were reported for sodium, potassium and copper which support the protein use as a nutritional supplement. On the other hand, nicotine is a very harmful alkaloid in tobacco plants and the LD 50 oral is 40mg in humans. The nicotine contents were analyzed by gas chromatography and it does not exceed the 7ug/ml

  10. 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

  11. 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 ...

  12. 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.

  13. Characterization of a series of anabaseine-derived compounds reveals that the 3-(4)-dimethylaminocinnamylidine derivative is a selective agonist at neuronal nicotinic alpha 7/125I-alpha-bungarotoxin receptor subtypes.

    Science.gov (United States)

    de Fiebre, C M; Meyer, E M; Henry, J C; Muraskin, S I; Kem, W R; Papke, R L

    1995-01-01

    Investigation of the naturally occurring, nicotinic agonist anabaseine and novel derivatives has shown that these compounds have cytoprotective and memory-enhancing effects. The hypothesis that these arise at least in part through actions on brain nicotinic receptors was evaluated by examining the ability of these compounds to displace the binding of nicotinic ligands and to affect the function of the alpha 4 beta 2 and alpha 7 receptor subtypes expressed in Xenopus oocytes. The derivative 3-(4)-dimethylaminocinnamylidine anabaseine (DMAC) was found to be a selective alpha 7 receptor agonist; it was more potent than nicotine, acetylcholine, anabaseine, and other derivatives at activating the alpha 7 receptor subtype, while displaying little agonist activity at alpha 4 beta 2 and other receptor subtypes. Compared with anabaseine and the other derivatives, DMAC was the most potent at displacing 125I-alpha-bungarotoxin binding (putative alpha 7) and the least potent at displacing [3H]cytisine binding (putative alpha 4 beta 2) to brain membranes. Independently of agonist activities, all of the novel compounds displayed secondary inhibitory activity at both receptor subtypes. At the alpha 4 beta 2 receptor subtype, inhibition by the 3-(2,4)-dimethoxybenzylidene derivative was enhanced by coapplication of acetylcholine, suggesting a noncompetitive form of inhibition. Anabaseine and nicotine prolonged the time course of activation of alpha 4 beta 2 receptors, compared with acetylcholine, suggesting sequential channel-blocking activity. As selective agonists, anabaseine derivatives such as DMAC may be useful for elucidating the function of alpha 7 nicotinic receptors, including their potential role(s) in the cytoprotective and memory-enhancing effects of nicotinic agents.

  14. 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.

  15. 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.

  16. 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.

  17. The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors

    DEFF Research Database (Denmark)

    Wieskopf, Jeffrey S; Mathur, Jayanti; Limapichat, Walrati

    2015-01-01

    expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia. We confirmed the importance of α6* (α6-containing) nAChRs by analyzing both gain- and loss-of-function mutants. We find that mechanical allodynia associated...... with neuropathic and inflammatory injuries is significantly altered in α6* mutants, and that α6* but not α4* nicotinic receptors are absolutely required for peripheral and/or spinal nicotine analgesia. Furthermore, we show that Chrna6's role in analgesia is at least partially due to direct interaction and cross...

  18. The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor ligands. Part 2: carboxamide derivatives with different spacer motifs.

    Science.gov (United States)

    Eibl, Christoph; Munoz, Lenka; Tomassoli, Isabelle; Stokes, Clare; Papke, Roger L; Gündisch, Daniela

    2013-12-01

    3,7-Diazabicyclo[3.3.1]nonane (bispidine) based nicotinic acetylcholine receptor (nAChR) ligands have been synthesized and evaluated for nAChRs interaction. Diverse spacer motifs were incorporated between the hydrogen bond acceptor (HBA) part and a variety of substituted (hetero)aryl moieties. Bispidine carboxamides bearing spacer motifs often showed high affinity in the low nanomolar range and selectivity for the α4β2(∗) nAChR. Compounds 15, 25, and 47 with Ki values of about 1 nM displayed the highest affinities for α4β2(∗) nAChR. All evaluated compounds are partial agonists or antagonists at α4β2(∗), with reduced or no effects on α3β4(∗) with the exception of compound 15 (agonist), and reduced or no effect at α7 and muscle subtypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. α7 Nicotinic acetylcholine receptor-mediated anti-inflammatory effect in a chronic migraine rat model via the attenuation of glial cell activation

    Directory of Open Access Journals (Sweden)

    Liu Q

    2018-06-01

    Full Text Available Qing Liu,1 Chaoyang Liu,1 Li Jiang,1 Maolin Li,1 Ting Long,1 Wei He,1 Guangcheng Qin,2 Lixue Chen,2 Jiying Zhou1 1Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; 2Laboratory Research Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China Background: Evidence suggests that the activation of α7 nicotinic acetylcholine receptor (α7nAChR can greatly decrease the neuroinflammation response. Neuroinflammation plays a pivotal role in the pathogenesis of chronic migraine (CM. Clinical observations also show that nicotine gum induces analgesic effects in migraine patients. However, whether α7nAChR is involved in CM is unclear.Objective: To investigate the role of α7nAChR in CM and provide a new therapeutic target for CM.Materials and methods: Thirty-six male Sprague–Dawley rats were distributed randomly into control, CM, PNU-282987, and α-bungarotoxin groups (n=9 rats in each group. The CM model was established by the recurrent daily administration of inflammatory soup on the dura over the course of 1 week. The hind paw threshold and facial allodynia were assessed by the von Frey test. The expression levels of α7nAChR, tumor necrosis factor-alpha, and interleukin-1 beta were analyzed by Western blot and real-time fluorescence quantitative polymerase chain reaction. The location of α7nAChR in the hippocampus was quantified by immunofluorescence, as well as the microglial and astrocyte alterations. Changes in the calcitonin gene-related peptide and the phosphorylated JNK protein among different groups were measured by Western blot.Results: We found that the expression of α7nAChR was reduced after repeated inflammatory soup administration. The increased expression of tumor necrosis factor-alpha, interleukin-1 beta, and calcitonin gene-related peptide in CM group were significantly decreased by PNU-282987 and aggravated by α-bungarotoxin. Moreover, PNU-282987

  20. Effects of (+/-)-4-[[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A), a selective ligand for nicotinic acetylcholine receptors, in tests of visual attention and distractibility in rats and monkeys.

    Science.gov (United States)

    Terry, A V; Risbrough, V B; Buccafusco, J J; Menzaghi, F

    2002-04-01

    Nicotine, a nonselective ligand for nicotinic acetylcholine receptors (nAChRs), has been shown to improve attention and reduce distractibility in humans. Although the numerous side effects induced by nicotine prevent its use as a therapeutic agent, it is hypothesized that subtype-selective nAChR ligands may offer a potential therapeutic benefit to humans with attention deficits. In this study, we evaluated the attention-enhancing properties of (+/-)-4-[[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A), a ligand selective for neuronal nAChRs with predominant activity at the human beta 4 subtype. SIB-1553A was evaluated in a test of attention (i.e., five-choice serial reaction time task or SRTT) and distractibility (i.e., delayed matching to sample task with distractor or DMTS-D) in adult rats and monkeys, respectively. SIB-1553A did not improve SRTT performance in normal rats, but reversed deficits induced by the N-methyl-D-aspartate (NMDA) antagonist dizocilpine. In the DMTS-D, SIB-1553A improved accuracy across several doses at the short delay intervals, which were affected most by distracting stimuli in adult monkeys. Subsequent testing with optimal doses for each monkey was also associated with significant improvements in DMTS-D accuracy at short delays, indicating the reproducibility of the drug effect. In both species, SIB-1553A had no significant effects on latencies for sample or choice selection and was not associated with adverse effects at efficacious doses. Although it remains to be further demonstrated, SIB-1553A may act through combined nicotinic and non-nicotinic mechanisms. Collectively, the present data suggest that in specific conditions SIB-1553A may improve certain aspects of attentional function in young adult rats and nonhuman primates without adverse side effects.

  1. Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression.

    Science.gov (United States)

    Liu, Jianhua; Yu, Li-Fang; Eaton, J Brek; Caldarone, Barbara; Cavino, Katie; Ruiz, Christina; Terry, Matthew; Fedolak, Allison; Wang, Daguang; Ghavami, Afshin; Lowe, David A; Brunner, Dani; Lukas, Ronald J; Kozikowski, Alan P

    2011-10-27

    Depression, a common neurological condition, is one of the leading causes of disability and suicide worldwide. Standard treatment, targeting monoamine transporters selective for the neurotransmitters serotonin and noradrenaline, is not able to help many patients that are poor responders. This study advances the development of sazetidine-A analogues that interact with α4β2 nicotinic acetylcholine receptors (nAChRs) as partial agonists and that possess favorable antidepressant profiles. The resulting compounds that are highly selective for the α4β2 subtype of nAChR over α3β4-nAChRs are partial agonists at the α4β2 subtype and have excellent antidepressant behavioral profiles as measured by the mouse forced swim test. Preliminary absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies for one promising ligand revealed an excellent plasma protein binding (PPB) profile, low CYP450-related metabolism, and low cardiovascular toxicity, suggesting it is a promising lead as well as a drug candidate to be advanced through the drug discovery pipeline.

  2. Differential expression and function of nicotinic acetylcholine receptors in subdivisions of medial habenula.

    Science.gov (United States)

    Shih, Pei-Yu; Engle, Staci E; Oh, Gyeon; Deshpande, Purnima; Puskar, Nyssa L; Lester, Henry A; Drenan, Ryan M

    2014-07-16

    Neuronal nAChRs in the medial habenula (MHb) to the interpeduncular nucleus (IPN) pathway are key mediators of nicotine's aversive properties. In this paper, we report new details regarding nAChR anatomical localization and function in MHb and IPN. A new group of knock-in mice were created that each expresses a single nAChR subunit fused to GFP, allowing high-resolution mapping. We find that α3 and β4 nAChR subunit levels are strong throughout the ventral MHb (MHbV). In contrast, α6, β2, β3, and α4 subunits are selectively found in some, but not all, areas of MHbV. All subunits were found in both ChAT-positive and ChAT-negative cells in MHbV. Next, we examined functional properties of neurons in the lateral and central part of MHbV (MHbVL and MHbVC) using brain slice patch-clamp recordings. MHbVL neurons were more excitable than MHbVC neurons, and they also responded more strongly to puffs of nicotine. In addition, we studied firing responses of MHbVL and MHbVC neurons in response to bath-applied nicotine. Cells in MHbVL, but not those in MHbVC, increased their firing substantially in response to 1 μm nicotine. Additionally, MHbVL neurons from mice that underwent withdrawal from chronic nicotine were less responsive to nicotine application compared with mice withdrawn from chronic saline. Last, we characterized rostral and dorsomedial IPN neurons that receive input from MHbVL axons. Together, our data provide new details regarding neurophysiology and nAChR localization and function in cells within the MHbV. Copyright © 2014 the authors 0270-6474/14/349789-14$15.00/0.

  3. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

    OpenAIRE

    Hirvonen, J; Goodwin, RS; Li, C-T; Terry, GE; Zoghbi, SS; Morse, C; Pike, VW; Volkow, ND; Huestis, MA; Innis, RB

    2011-01-01

    Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke ca...

  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. 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

  6. 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...

  7. Nicotine-Induced Effects on Nicotinic Acetylcholine Receptors (nAChRs), Ca2+ and Brain-Derived Neurotrophic Factor (BDNF) in STC-1 Cells.

    Science.gov (United States)

    Qian, Jie; Mummalaneni, Shobha K; Alkahtani, Reem M; Mahavadi, Sunila; Murthy, Karnam S; Grider, John R; Lyall, Vijay

    2016-01-01

    In addition to the T2R bitter taste receptors, neuronal nicotinic acetylcholine receptors (nAChRs) have recently been shown to be involved in the bitter taste transduction of nicotine, acetylcholine and ethanol. However, at present it is not clear if nAChRs are expressed in enteroendocrine cells other than beta cells of the pancreas and enterochromaffin cells, and if they play a role in the synthesis and release of neurohumoral peptides. Accordingly, we investigated the expression and functional role of nAChRs in enteroendocrine STC-1 cells. Our studies using RT-PCR, qRT-PCR, immunohistochemical and Western blotting techniques demonstrate that STC-1 cells express several α and β nAChR subunits. Exposing STC-1 cells to nicotine acutely (24h) or chronically (4 days) induced a differential increase in the expression of nAChR subunit mRNA and protein in a dose- and time-dependent fashion. Mecamylamine, a non-selective antagonist of nAChRs, inhibited the nicotine-induced increase in mRNA expression of nAChRs. Exposing STC-1 cells to nicotine increased intracellular Ca2+ in a dose-dependent manner that was inhibited in the presence of mecamylamine or dihydro-β-erythroidine, a α4β2 nAChR antagonist. Brain-derived neurotrophic factor (BDNF) mRNA and protein were detected in STC-1 cells using RT-PCR, specific BDNF antibody, and enzyme-linked immunosorbent assay. Acute nicotine exposure (30 min) decreased the cellular content of BDNF in STC-1 cells. The nicotine-induced decrease in BDNF was inhibited in the presence of mecamylamine. We also detected α3 and β4 mRNA in intestinal mucosal cells and α3 protein expression in intestinal enteroendocrine cells. We conclude that STC-1 cells and intestinal enteroendocrine cells express nAChRs. In STC-1 cells nAChR expression is modulated by exposure to nicotine in a dose- and time-dependent manner. Nicotine interacts with nAChRs and inhibits BDNF expression in STC-1 cells.

  8. 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.

  9. Evaluating Nicotine Levels Selection and Patterns of Electronic Cigarette use in a Group of “Vapers” Who Had Achieved Complete Substitution of Smoking

    Directory of Open Access Journals (Sweden)

    Konstantinos E. Farsalinos

    2013-01-01

    Full Text Available Background Electronic cigarettes (ECs are alternative-to-smoking nicotine delivery devices; consumers (commonly called vapers use them in order to reduce or completely substitute smoking. The European Commission has released a proposal for a new Tobacco Product Directive that might reduce availability of nicotine-containing products, including ECs. In this study, the EC use patterns in subjects who have completely substituted smoking with EC use were examined by personal interviews. The study focused on nicotine levels used in order to achieve smoking cessation, reported benefits, associated side effects, and estimation of EC dependence compared with smoking. Methods Participants were 111 subjects who had completely substituted smoking with EC use for at least 1 month. Smoking abstinence was validated by measuring blood carboxyhemoglobin levels. Nicotine levels at initiation of EC use, at time of smoking cessation, and at time of interview were recorded. Dependence potential was assessed by asking the first question of the Fagerström Test for Cigarette Dependence (time until smoking the first cigarette and until first use of EC in the morning and questions about perceived past dependence on tobacco cigarettes and present dependence on EC. Results Forty-two percent of participants reported quitting smoking during the first month of EC use. Liquids with nicotine concentration >15 mg/mL were used by 74% of users at initiation of EC use, while 16.2% had to increase the initial nicotine levels in order to achieve complete smoking abstinence. Seventy-two participants (64.9% reported that from the time of smoking cessation to the time of the interview (8 months median duration of EC use they reduced the nicotine concentration they were consuming; however, only 12% of the total sample was using ≤5 mg/mL nicotine concentration at the time of the interview. Side effects were mild and temporary. The vast majority of participants reported better exercise

  10. 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.

  11. 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

  12. 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.

  13. The selective alpha7 nicotinic acetylcholine receptor agonist A-582941 activates immediate early genes in limbic regions of the forebrain

    DEFF Research Database (Denmark)

    Thomsen, M S; Mikkelsen, J D; Timmermann, D B

    2008-01-01

    to study whether alpha7 nAChR stimulation activates brain regions involved in cognition in juvenile as well as adult individuals. Here, we compared the effects of the novel and selective alpha7 nAChR agonist 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole (A-582941) in the juvenile...... regions critically involved in working memory and attention. Furthermore, this effect is more pronounced in juvenile than adult rats, indicating that the juvenile forebrain is more responsive to alpha7 nAChR stimulation. This observation may be relevant in the treatment of juvenile-onset schizophrenia....

  14. 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)

  15. Radiosynthesis and ex vivo evaluation of [{sup 11}C]-SIB-1553A as a PET radiotracer for {beta}4 selective subtype nicotinic acetylcholine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Sobrio, Franck [CEA, DSV, I2BM, CINAPS, LDMTEP, Caen, F-14074 (France); Universite de Caen Basse-Normandie, UMR CEA E2, Centre Cyceron, Caen, F-14074 (France)], E-mail: sobrio@cyceron.fr; Quentin, Thomas; Dhilly, Martine; Bourdier, Thomas; Tymciu, Sylvie; Debruyne, Daniele; Barre, Louisa [CEA, DSV, I2BM, CINAPS, LDMTEP, Caen, F-14074 (France); Universite de Caen Basse-Normandie, UMR CEA E2, Centre Cyceron, Caen, F-14074 (France)

    2008-04-15

    [{sup 11}C]-SIB-1553A (({+-})-4-[2-((N-[{sup 11}C]-methyl)-2-pyrrolidinyl)ethyl]thiophenol) was labelled with carbon-11 (t{sub 1/2}=20.4 min) and evaluated in vivo as potential radiotracer for noninvasive assessment of the {beta}4 subunit nicotinic acetylcholine neurotransmission system with positron emission tomography (PET). The labelling precursor was obtained within five steps from N-Boc-prolinal in 45-56% overall yields. The radiosynthesis of [{sup 11}C]-SIB-1553A was achieved by a selective N-[{sup 11}C]-methylation in 32 min with a radiochemical purity greater than 97%, 7.5-30 GBq/{mu}mol of specific radioactivity and 55-65% radiochemical yield (decay corrected, based on [{sup 11}C]methyl iodide). The ex vivo pharmacological profile of [{sup 11}C]-SIB-1553A was evaluated in rats with biodistribution studies in organs and in brain structures by autoradiography. The radiotracer uptake in the brain reached 0.49 %ID/g at 10 min and no brain radiometabolite was detected 40 min after intravenous injection. The quantification of radioactivity in various cerebral structures indicated a significantly higher radioactivity level at 15 min than at 30 min. Among the {beta}4 nAChR subunit-rich structures studied in the rat brain, only the thalamus at 15 and 30 min and the hippocampus at 30 min showed significantly higher uptake. Moreover, competition studies performed with SIB-1553A (15 min before the radiotracer injection) revealed only a low specific binding estimated to 7% of the total binding at 15 min and 13% at 30 min.

  16. Carbon-11 labelling of S38419, a novel alpha-4-beta-2-selective ligand for PET imaging of nicotinic acetylcholine receptors

    International Nuclear Information System (INIS)

    Dolle, F.; Demphel, St.; Saba, W.; Schollhorn-Peyronneau, M.A.; Deverre, J.R.; Bottlaender, M.; Valette, H.; Charton, Y.; Goldstein, S.; Lestage, P.

    2011-01-01

    Complete text of publication follows: Objectives: There is considerable evidence that a variety of functions and disorders (e.g. Alzheimer's and Parkinson's disease) of the CNS is associated with the neuronal nicotinic acetylcholine receptors and particularly with the subtypes containing α4 and β2 subunits (nAChRs). The consistent and severe loss of these receptors in the diseases mentioned above has prompted extensive efforts, over more than two decades now, into the design of PET radioligands for non-invasive in vivo imaging of these receptors and the quantification of their density in the human brain. Not only analogues of the alkaloid epibatidine were labelled with positron-emitters but also series of 3-pyridyl ethers bearing either the traditional nicotinic-like pyrrolidine ring (e.g. [ 11 C]A-84543) or the azetidine motive (e.g. 2-[ 18 F]F-A-85380). Novel structures, still possessing high affinity and selectivity for nAChRs but not displaying any saturated, nitrogen-containing, 5- or 4-membered rings were also reported (e.g. [ 11 C]p-PVPMEMA). Recently, a novel series of highly potent α4β2-selective 3-pyridinamines (exhibiting a cyclopropane ring together with a non-cyclic amino function) has been developed by Servier Laboratories. Within this series, S38419 (1, N-methyl-N-[[1-(methylamino)cyclopropyl]methyl]pyridin-3-amine) was selected on the basis of its pharmacological and biological characteristics as a potent candidate for PET imaging and was isotopically labelled with carbon-11 using [ 11 C]methyl triflate. Methods: Carbon-11 labelling of S38419 (1) was performed using a TRACERLab FX-C Pro synthesizer (GEMS) and comprises (1) trapping at -10 C of [ 11 C]MeOTf in DMF (0.3 mL) containing the nor-derivative (N-demethylated, 1.8-2.0 mg); (2) heating at 120 C for 2 min; (3) taking up the residue in 1.0 mL of the HPLC mobile phase; (4) purification using semi-preparative reversed-phase HPLC (Waters Symmetry R C-18 - eluent: CH 3 CN / H 2 O / TEA: 20 / 80

  17. 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.

  18. Identification and in vitro pharmacological characterization of a novel and selective α7 nicotinic acetylcholine receptor agonist, Br-IQ17B.

    Science.gov (United States)

    Tang, Jing-shu; Xie, Bing-xue; Bian, Xi-ling; Xue, Yu; Wei, Ning-ning; Zhou, Jing-heng; Hao, Yu-chen; Li, Gang; Zhang, Liang-ren; Wang, Ke-wei

    2015-07-01

    Alpha7-nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated Ca(2+)-permeable ion channel implicated in cognition and neuropsychiatric disorders. Activation of α7 nAChR improves learning, memory, and sensory gating in animal models. To identify novel α7 nAChR agonists, we synthesized a series of small molecules and characterized a representative compound, Br-IQ17B, N-[(3R)-1-azabicyclo[2,2,2]oct-3-yl]-5-bromoindolizine-2-carboxamide, which specifically activates α7 nAChR. Two-electrode voltage clamp (TEVC) recordings were primarily used for screening in Xenopus oocytes expressing human α7 nAChR. Assays, including radioisotope ligand binding, Western blots, whole-cell recordings of hippocampal culture neurons, and spontaneous IPSC recordings of brain slices, were also utilized to evaluate and confirm the specific activation of α7 nAChR by Br-IQ17B. Br-IQ17B potently activates α7 nAChR with an EC50 of 1.8±0.2 μmol/L. Br-IQ17B is selective over other subtypes such as α4β2 and α3β4, but it blocks 5-HT3A receptors. Br-IQ17B displaced binding of the α7 blocker [(3)H]-MLA to hippocampal crude membranes with a Ki of 14.9±3.2 nmol/L. In hippocampal neurons, Br-IQ17B evoked α7-like currents that were inhibited by MLA and enhanced in the presence of the α7 PAM PNU-120596. In brain slice recordings, Br-IQ17B enhanced GABAergic synaptic transmission in CA1 neurons. Mechanistically, Br-IQ17B increased ERK1/2 phosphorylation that was MLA-sensitive. We identified the novel, potent, and selective α7 agonist Br-IQ17B, which enhances synaptic transmission. Br-IQ17B may be a helpful tool to understand new aspects of α7 nAChR function, and it also has potential for being developed as therapy for schizophrenia and cognitive deficits.

  19. Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Dallanoce, Clelia; Magrone, Pietro; Matera, Carlo

    2011-01-01

    A set of racemic spirocyclic quinuclidinyl-¿(2) -isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (a7) and heteromeric (a4ß2) nicotinic acetylcholine receptors. ¿(2) -Isoxazol...

  20. PASS assisted prediction and pharmacological evaluation of novel nicotinic analogs for nootropic activity in mice.

    Science.gov (United States)

    Khurana, Navneet; Ishar, Mohan Pal Singh; Gajbhiye, Asmita; Goel, Rajesh Kumar

    2011-07-15

    The aim of present study is to predict the probable nootropic activity of novel nicotine analogues with the help of computer program, PASS (prediction of activity spectra for substances) and evaluate the same. Two compounds from differently substituted pyridines were selected for synthesis and evaluation of nootropic activity based on their high probable activity (Pa) value predicted by PASS computer program. Evaluation of nootropic activity of compounds after acute and chronic treatment was done with transfer latency (TL) and step down latency (SDL) methods which showed significant nootropic activity. The effect on scopolamine induced amnesia was also observed along with their acetylcholine esterase inhibitory activity which also showed positive results which strengthened their efficacy as nootropic agents through involvement of cholinergic system. This nootropic effect was similar to the effect of nicotine and donepezil used as standard drugs. Muscle coordination and locomotor activity along with their addiction liability, safety and tolerability studies were also evaluated. These studies showed that these compounds are well tolerable and safe over a wide range of doses tested along with the absence of withdrawal effect which is present in nicotine due to its addiction liability. The study showed that these compounds are true nicotine analogs with desirable efficacy and safety profile for their use as effective nootropic agents. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. 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

  2. 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.

  3. 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

  4. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

    Science.gov (United States)

    Hirvonen, J; Goodwin, R S; Li, C-T; Terry, G E; Zoghbi, S S; Morse, C; Pike, V W; Volkow, N D; Huestis, M A; Innis, R B

    2012-06-01

    Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

  5. 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.

  6. 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

  7. Selective amotivation deficits following chronic psychosocial stress in mice.

    Science.gov (United States)

    Tsai Cabal, Alejandro; Ioanas, Horea-Ioan; Seifritz, Erich; Saab, Bechara J

    2017-01-15

    Amotivation is a major symptom of several psychiatric disorders. However, which specific motivations are most affected in various illnesses is not well understood. In major depressive disorder (MDD), anecdotal evidence suggests the motivation to explore may be especially affected, but direct evidence from either patients or animal models is lacking. To investigate the potential for, and nature of, exploratory drive deficits in MDD, we subjected mice to a chronic social defeat (CSD) manipulation that gives rise to a MDD-like behavioural ensemble, and performed a behavioural battery to examine bodyweight homeostasis, ambulation, anxiety, exploratory behaviour motivated by either novelty or fear, and short-term memory. Consistent with previous reports, we found a disruption of bodyweight homeostasis and reduced ambulation following CSD treatment, but we found no evidence for anxiogenic effects or impairments in short-term memory. Surprisingly, we also observed profoundly delayed and diminished exploration of novel, safe space following CSD, while exploration motivated by fear remained intact. These results extend our knowledge of the behavioural phenotypes in mice resulting from CSD by homing in on specific motivational drives. In MDD patients, reduced exploration could compound disease symptomatology by preventing engagement in what could be rewarding exploration experiences, and targeting deficits in the motivation to explore may represent a novel avenue for treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. 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.

  9. Dasatinib for the treatment of chronic myeloid leukemia: patient selection and special considerations.

    Science.gov (United States)

    Keskin, Dilek; Sadri, Sevil; Eskazan, Ahmet Emre

    2016-01-01

    Dasatinib is one of the second-generation tyrosine kinase inhibitors used in imatinib resistance and/or intolerance, as well as in the frontline setting in patients with chronic myeloid leukemia-chronic phase, and also in patients with advanced disease. It is also utilized in Philadelphia chromosome-positive acute lymphocytic leukemia. While choosing the appropriate tyrosine kinase inhibitor (ie, dasatinib) for each individual patient, comorbidities and BCR-ABL1 kinase domain mutations should always be taken into consideration, among other things. This review mainly focuses on patient selection prior to dasatinib administration in the treatment of chronic myeloid leukemia.

  10. Selecting the Best Frontline Treatment in Chronic Myeloid Leukemia

    Science.gov (United States)

    Yilmaz, Musa; Abaza, Yasmin; Jabbour, Elias

    2017-01-01

    With the discovery of Philadelphia chromosome, understanding of chronic myeloid leukemia (CML) pathobiology has tremendously increased. Development of tyrosine kinase inhibitors (TKI) targeting the BCR/ABL1 oncoprotein has changed the landscape of the disease. Today, the expected survival of CML patients, if properly managed, is likely to be similar to the general population. Imatinib is the first approved TKI in CML treatment, and for several years, it was the only option in the frontline setting. Four years ago, second generation TKIs (nilotinib and dasatinib) were approved as alternative frontline options. Now, clinicians are faced the challenge of making decision for which TKI to chose upfront. Second generation TKIs have been demonstrated to induce deeper and faster responses compared to imatinib, however, none of 3 TKIs have been shown to have a clear survival advantage, they all are reasonable options. In contrast, when considering therapy in individual patients, the case may be stronger for a specific TKI. Co-morbidities of the patient and side effect profile of the TKI of interest should be an important consideration in decision making. At present, the cost nilotinib or dasatinib is not remarkably different from imatinib. However, patent for imatinib is expected to expire soon, and it will be available as a generic. Clinicians, then, need to weigh the advantages some patients gain with nilotinib or dasatinib in the frontline setting against the difference in cost. Whatever TKI is chosen as frontline, intolerance, non-compliance or treatment failure should be recognized early as a prompt intervention increases the chance of achieving best possible response. PMID:25921387

  11. 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.

  12. 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.

  13. 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 ...

  14. 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 ...

  15. 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.

  16. 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.

  17. 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.

  18. Muscle activation during selected strength exercises in women with chronic neck muscle pain

    DEFF Research Database (Denmark)

    Andersen, Lars L; Kjaer, Michael; Andersen, Christoffer H

    2008-01-01

    selected strengthening exercises in women undergoing rehabilitation for chronic neck muscle pain (defined as a clinical diagnosis of trapezius myalgia). SUBJECTS: The subjects were 12 female workers (age=30-60 years) with a clinical diagnosis of trapezius myalgia and a mean baseline pain intensity of 5......BACKGROUND AND PURPOSE: Muscle-specific strength training has previously been shown to be effective in the rehabilitation of chronic neck muscle pain in women. The aim of this study was to determine the level of activation of the neck and shoulder muscles using surface electromyography (EMG) during...... muscle pain. Several of the strength exercises had high activation of neck and shoulder muscles in women with chronic neck pain. These exercises can be used equally in the attempt to achieve a beneficial treatment effect on chronic neck muscle pain....

  19. 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.

  20. 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

  1. 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...

  2. 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)

  3. Surgical thromboendarterectomy for chronic thromboembolic pulmonary hypertension using circulatory arrest with selective antegrade cerebral perfusion

    NARCIS (Netherlands)

    Zeebregts, CJAM; Dossche, KM; Morshuis, WJ; Knaepen, PJ; Schepens, MAAM

    The use of circulatory arrest with selective antegrade cerebral perfusion is described in a 59-year-old man who underwent thrombendarterectomy for chronic thromboembolic pulmonary hypertension. The postoperative course was uneventful. The described surgical technique may prevent the patient from

  4. The Chronic and Acute Effects of Exercise Upon Selected Blood Measures.

    Science.gov (United States)

    Roitman, J. L.; Brewer, J. P.

    This study investigated the effects of chronic and acute exercise upon selected blood measures and indices. Nine male cross-country runners were studied. Red blood count, hemoglobin, and hematocrit were measured using standard laboratory techniques; mean corpuscular volume (MCV), mean corpuscular hemoglobin, and mean corpuscular hemoglobin…

  5. 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

  6. 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.

  7. 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...

  8. Total pancreatectomy for recurrent acute and chronic pancreatitis: a critical review of patient selection criteria

    Science.gov (United States)

    Faghih, Mahya; Gonzalez, Francisco Garcia; Makary, Martin A.; Singh, Vikesh K.

    2018-01-01

    Purpose of review Critical review of the indications for total pancreatectomy and highlight limitations in current diagnostic criteria for chronic pancreatitis. Recent findings The diagnosis of noncalcific chronic pancreatitis remains controversial because of an overreliance on nonspecific imaging and laboratories findings. Endoscopic ultrasound, s-magnetic resonance cholangiopancreatography, and/or endoscopic pancreatic function testing are often used to diagnose noncalcific chronic pancreatitis despite the fact that there is no gold standard for this condition. Abdominal pain is not specific for chronic pancreatitis and is more likely to be encountered in patients with functional gastrointestinal disorders based on the high incidence of these conditions. The duration of pain and opioid analgesic use results in central sensitization that adversely affects pain outcomes after total pancreatectomy. An alcoholic cause is associated with poorer pain outcomes after total pancreatectomy. Summary The lack of a gold standard for noncalcific chronic pancreatitis limits the diagnostic accuracy of imaging and laboratory tests. The pain of chronic pancreatitis is nonspecific and is affected by duration, preoperative opioid use, and cause. These factors will need to be considered in the development of future selection criteria for this morbid surgery. PMID:28700371

  9. 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.

  10. 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.

  11. 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.

  12. Selected aspects of nursing care for an elderly patient with chronic obstructive pulmonary disease

    OpenAIRE

    Budnik, Marta; Galikowska, Anna; Marzec, Izabela; Balcerak, Dominika; Kobus, Edyta; Posieczek, Zuzanna

    2017-01-01

    Budnik Marta, Galikowska Anna, Marzec Izabela, Balcerak Dominika, Kobus Edyta, Posieczek Zuzanna. Selected aspects of nursing care for an elderly patient with chronic obstructive pulmonary disease. Journal of Education, Health and Sport. 2017;7(6):34-44. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.802926 http://ojs.ukw.edu.pl/index.php/johs/article/view/4501 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation...

  13. 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.

  14. 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.

  15. The α7-nACh nicotinic receptor and its role in memory and selected diseases of the central nervous system

    Directory of Open Access Journals (Sweden)

    Urszula Baranowska

    2017-07-01

    Full Text Available α7-nACh is one of the major nicotinic cholinergic receptor subtypes found in the brain. It is broadly expressed in the hippocampal and cortical neurons, the regions which play a key role in memory formation. Although α7-nACh receptors may serve as postsynaptic receptors mediating classical neurotransmission, they usually function as presynaptic modulators responsible for the release of other neurotransmitters, such as glutamate, γ-aminobutyric acid, dopamine, and norepinephrine. They can, therefore, affect a wide array of neurobiological functions. In recent years, research has found that a large number of agonists and positive allosteric modulators of α7-nAChR induce beneficial effects on learning and memory. Consistently, mice deficient in chrna7 (the gene encoding α7-nAChR protein, are characterized by memory deficits. In addition, decreased expression and function of α7-nAChR is associated agoniwith many neurological diseases including schizophrenia, bipolar disorder, learning disability, attention deficit hyperactivity disorder, Alzheimer disease, autism, and epilepsy. In the recent years many animal experiments and clinical trials using α7-nAChR ligands were conducted. The results of these studies strongly indicate that agonists and positive allosteric modulators of α7-nAChR are promising therapeutic agents for diseases associated with cognitive deficits.

  16. 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

  17. Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.

    Science.gov (United States)

    Yap, Christina; Pettitt, Andrew; Billingham, Lucinda

    2013-07-03

    As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon's two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.

  18. 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.

  19. 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

  20. Chronic thromboembolic pulmonary hypertension: diagnostic impact of multislice-CT and selective pulmonary-DSA

    International Nuclear Information System (INIS)

    Pitton, M.B.; Kemmerich, G.; Herber, S.; Schweden, F.; Thelen, M.; Mayer, E.

    2002-01-01

    Purpose: To evaluate the diagnostic impact of multislice-CT and selective pulmonary DSA in chronic thromboembolic pulmonary hypertension (CTEPH). Methods: 994 vessel segments of 14 consecutive patients with CTEPH were investigated with multislice-CT (slice thickness 3 mm, collimation 2.5 mm, reconstruction intervall 2 mm) and selective pulmonary DSA posterior-anterior, 45 oblique, and lateral projection. Analysis was performed by 2 investigators independently for CT and DSA. Diagnostic criteria were occlusions and non-occlusive changes like webs and bands, irregularities of the vessel wall, diameter reduction and thromboembolic depositions at different levels from central pulmonary arteries to subsegmental arteries. Reference diagnosis was made by synopsis of CT and DSA by consensus. Results: Concerning patency CT and DSA showed concordant findings overall in 88.9%, 92.9% for segmental arteries and 85.4% for subsegmental arteries. Concerning any thromboembolic changes, multislice-CT was significantly inferior to selective DSA (concordance 67.0% overall, 70.4% for segments and 63.6% for subsegments). Non-occlusive changes of the vessels were significantly underdiagnosed by CT (concordance of CT versus DSA: 23.1%). Conclusion: Multislice-CT and selective pulmonary DSA are equivalent for diagnosis of vessel occlusions at the level of segmental and subsegmental arteries. However, for visualisation of the non-occlusive thromboembolic changes of the vessel wall selective pulmonary DSA is still superior compared to multislice-CT. Multislice-CT and selective pulmonary DSA are complementary tools for diagnosis and treatment planning of chronic thromboembolic pulmonary hypertension (CTEPH). (orig.) [de

  1. The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: the influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents.

    Science.gov (United States)

    Eibl, Christoph; Tomassoli, Isabelle; Munoz, Lenka; Stokes, Clare; Papke, Roger L; Gündisch, Daniela

    2013-12-01

    3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for α4β2(∗) were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for α4β2(∗) possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Nicotine disrupts safety learning by enhancing fear associated with a safety cue via the dorsal hippocampus.

    Science.gov (United States)

    Connor, David A; Kutlu, Munir G; Gould, Thomas J

    2017-07-01

    Learned safety, a learning process in which a cue becomes associated with the absence of threat, is disrupted in individuals with post-traumatic stress disorder (PTSD). A bi-directional relationship exists between smoking and PTSD and one potential explanation is that nicotine-associated changes in cognition facilitate PTSD emotional dysregulation by disrupting safety associations. Therefore, we investigated whether nicotine would disrupt learned safety by enhancing fear associated with a safety cue. In the present study, C57BL/6 mice were administered acute or chronic nicotine and trained over three days in a differential backward trace conditioning paradigm consisting of five trials of a forward conditioned stimulus (CS)+ (Light) co-terminating with a footshock unconditioned stimulus followed by a backward CS- (Tone) presented 20 s after cessation of the unconditioned stimulus. Summation testing found that acute nicotine disrupted learned safety, but chronic nicotine had no effect. Another group of animals administered acute nicotine showed fear when presented with the backward CS (Light) alone, indicating the formation of a maladaptive fear association with the backward CS. Finally, we investigated the brain regions involved by administering nicotine directly into the dorsal hippocampus, ventral hippocampus, and prelimbic cortex. Infusion of nicotine into the dorsal hippocampus disrupted safety learning.

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

    Directory of Open Access Journals (Sweden)

    Ian Mahar

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

  4. Low-educated women with chronic pain were less often selected to multidisciplinary rehabilitation programs.

    Directory of Open Access Journals (Sweden)

    Anne Hammarström

    Full Text Available BACKGROUND: There is a lack of research about a potential education-related bias in assessment of patients with chronic pain. The aim of this study was to analyze whether low-educated men and women with chronic pain were less often selected to multidisciplinary rehabilitation than those with high education. METHODS: The population consisted of consecutive patients (n = 595 women, 266 men referred during a three-year period from mainly primary health care centers for a multidisciplinary team assessment at a pain rehabilitation clinic at a university hospital in Northern Sweden. Patient data were collected from the Swedish Quality Registry for Pain Rehabilitation National Pain Register. The outcome variable was being selected by the multidisciplinary team assessment to a multidisciplinary rehabilitation program. The independent variables were: sex, age, born outside Sweden, education, pain severity as well as the hospital, anxiety and depression scale (HADS. RESULTS: Low-educated women were less often selected to multidisciplinary rehabilitation programs than high-educated women (OR 0.55, CI 0.30-0.98, even after control for age, being born outside Sweden, pain intensity and HADS. No significant findings were found when comparing the results between high- and low-educated men. CONCLUSION: Our findings can be interpreted as possible discrimination against low-educated women with chronic pain in hospital referrals to pain rehabilitation. There is a need for more gender-theoretical research emphasizing the importance of taking several power dimensions into account when analyzing possible bias in health care.

  5. 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.

  6. Resistance to Inhibitors of Cholinesterase 3 (Ric-3 Expression Promotes Selective Protein Associations with the Human α7-Nicotinic Acetylcholine Receptor Interactome.

    Directory of Open Access Journals (Sweden)

    Matthew J Mulcahy

    Full Text Available The α7-nicotinic acetylcholine receptor (α7-nAChR is a ligand-gated ion channel widely expressed in vertebrates and is associated with numerous physiological functions. As transmembrane ion channels, α7-nAChRs need to be expressed on the surface of the plasma membrane to function. The receptor has been reported to associate with proteins involved with receptor biogenesis, modulation of receptor properties, as well as intracellular signaling cascades and some of these associated proteins may affect surface expression of α7-nAChRs. The putative chaperone resistance to inhibitors of cholinesterase 3 (Ric-3 has been reported to interact with, and enhance the surface expression of, α7-nAChRs. In this study, we identified proteins that associate with α7-nAChRs when Ric-3 is expressed. Using α-bungarotoxin (α-bgtx, we isolated and compared α7-nAChR-associated proteins from two stably transfected, human tumor-derived cell lines: SH-EP1-hα7 expressing human α7-nAChRs and the same cell line further transfected to express Ric-3, SH-EP1-hα7-Ric-3. Mass spectrometric analysis of peptides identified thirty-nine proteins that are associated with α7-nAChRs only when Ric-3 was expressed. Significantly, and consistent with reports of Ric-3 function in the literature, several of the identified proteins are involved in biological processes that may affect nAChR surface expression such as post-translational processing of proteins, protein trafficking, and protein transport. Additionally, proteins affecting the cell cycle, the cytoskeleton, stress responses, as well as cyclic AMP- and inositol triphosphate-dependent signaling cascades were identified. These results illuminate how α-bgtx may be used to isolate and identify α7-nAChRs as well as how the expression of chaperones such as Ric-3 can influence proteins associating with α7-nAChRs. These associating proteins may alter activities of α7-nAChRs to expand their functionally-relevant repertoire as

  7. 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.

  8. Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits.

    Science.gov (United States)

    Renteria, Rafael; Baltz, Emily T; Gremel, Christina M

    2018-01-15

    Addiction involves a predominance of habitual control mediated through action selection processes in dorsal striatum. Research has largely focused on neural mechanisms mediating a proposed progression from ventral to dorsal lateral striatal control in addiction. However, over reliance on habit striatal processes may also arise from reduced cortical input to striatum, thereby disrupting executive control over action selection. Here, we identify novel mechanisms through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts top-down control over goal-directed action selection processes to produce habits. We find CIE results in decreased excitability of orbital frontal cortex (OFC) excitatory circuits supporting goal-directed control, and, strikingly, selectively reduces OFC output to the direct output pathway in dorsal medial striatum. Increasing the activity of OFC circuits restores goal-directed control in CIE-exposed mice. Our findings show habitual control in alcohol dependence can arise through disrupted communication between top-down, goal-directed processes onto basal ganglia pathways controlling action selection.

  9. 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.

  10. 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.

  11. Practical considerations and patient selection for intrathecal drug delivery in the management of chronic pain

    Directory of Open Access Journals (Sweden)

    Saulino M

    2014-11-01

    Full Text Available Michael Saulino,1,2 Philip S Kim,3,4 Erik Shaw5 1MossRehab, Elkins Park, PA, USA; 2Department of Rehabilitation Medicine, Jefferson Medical College, Philadelphia, PA, USA; 3Helen F Graham Cancer Center, Christiana Care Health System, Newark, DE, USA; 4Center for Interventional Pain Spine, LLC., Bryn Mawr, PA, USA; 5Shepherd Pain Institute, Shepherd Center, Atlanta, GA, USA Abstract: Chronic pain continues to pose substantial and growing challenges for patients, caregivers, health care professionals, and health care systems. By the time a patient with severe refractory pain sees a pain specialist for evaluation and management, that patient has likely tried and failed several nonpharmacologic and pharmacologic approaches to pain treatment. Although relegated to one of the interventions of “last resort”, intrathecal drug delivery can be useful for improving pain control, optimizing patient functionality, and minimizing the use of systemic pain medications in appropriately selected patients. Due to its clinical and logistical requirements, however, intrathecal drug delivery may fit poorly into the classic pain clinic/interventional model and may be perceived as a "critical mass" intervention that is feasible only for large practices that have specialized staff and appropriate office resources. Potentially, intrathecal drug delivery may be more readily adopted into larger practices that can commit the necessary staff and resources to support patients' needs through the trialing, initiation, monitoring, maintenance, and troubleshooting phases of this therapy. Currently, two agents – morphine and ziconotide – are approved by the United States Food and Drug Administration for long-term intrathecal delivery. The efficacy and safety profiles of morphine have been assessed in long-term, open-label, and retrospective studies of >400 patients with chronic cancer and noncancer pain types. The efficacy and safety profiles of ziconotide have been

  12. The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats.

    Science.gov (United States)

    Hajós, M; Hurst, R S; Hoffmann, W E; Krause, M; Wall, T M; Higdon, N R; Groppi, V E

    2005-03-01

    Schizophrenic patients are thought to have an impaired ability to process sensory information. This deficit leads to disrupted auditory gating measured electrophysiologically as a reduced suppression of the second of paired auditoryevoked responses (P50) and is proposed to be associated with decreased function and/or expression of the homomeric alpha7 nicotinic acetylcholine receptor (nAChR). Here, we provide evidence that N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), a novel selective agonist of the alpha7 nAChR, evoked whole-cell currents from cultured rat hippocampal neurons that were sensitive to the selective alpha7 nAChR antagonist methyllycaconitine (MLA) and enhanced GABAergic synaptic activity when applied to hippocampal slices. Amphetamine-induced sensory gating deficit, determined by auditory-evoked potentials in hippocampal CA3 region, was restored by systemic administration of PNU-282987 in chloral hydrate-anesthetized rats. Auditory gating of rat reticular thalamic neurons was also disrupted by amphetamine; however, PNU-282987 normalized gating deficit only in a subset of tested neurons (6 of 11). Furthermore, PNU-282987 improved the inherent hippocampal gating deficit occurring in a subpopulation of anesthetized rats, and enhanced amphetamine-induced hippocampal oscillation. We propose that the alpha7 nAChR agonist PNU-282987, via modulating/enhancing hippocampal GABAergic neurotransmission, improves auditory gating and enhances hippocampal oscillatory activity. These results provide further support for the concept that drugs that selectively activate alpha7 nAChRs may offer a novel, potential pharmacotherapy in treatment of schizophrenia.

  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. 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...

  15. 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.

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

    International Nuclear Information System (INIS)

    Shigenaga, M.K.

    1989-01-01

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

  17. Nicotine intake and problem solving strategies are modified during a cognitively demanding water maze task in rats.

    Science.gov (United States)

    Nesil, Tanseli; Kanit, Lutfiye; Pogun, Sakire

    2015-11-01

    Nicotine is the major addictive component in tobacco, and despite well-established adverse health effects of tobacco addiction, some smokers have difficulty quitting. The acute cognitive enhancement and/or the amelioration of the cognitive disruption during withdrawal that some smokers experience after smoking are among important factors that hinder quit attempts. The animal model presented in the current study is comparable to the human smoking condition although nicotine intake routes are different. Rats were exposed to a free choice of oral nicotine starting at adolescence, and given a water maze (WM) task as adults. This design allowed us to see if rats alter their nicotine intake during the WM task and if nicotine preference and intake modify abilities and strategies rats use for problem solving. Male and female rats were exposed to a free choice of oral nicotine/water for 24weeks, starting at five weeks of age. After this period, they were selected based on their nicotine intake and, together with control animals that received only water, were subjected to a place-learning task in the WM. Free-choice nicotine exposure continued during WM testing. Following acquisition, the probe trial presented the rats with a choice between using two different strategies for problem solving. Nicotine supported acquisition and rats increased their nicotine intake during WM testing; this effect was more pronounced in male rats with minimum nicotine preference and intake. Furthermore, nicotine modified the "female type" strategy in solving the place-learning task and nicotine treated female rats, unlike control females, behaved like males. The increase in nicotine intake during mental engagement, and the sexually dimorphic effect of nicotine on problem solving strategies that we have observed in rats, may suggest that implementing sex-specific smoking cessation approaches, especially under stressful and cognitively demanding conditions, may be useful in helping smokers quit

  18. 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.

  19. Effects of pharmacological manipulation of the kappa opioid receptors on the aversive effects of nicotine.

    Science.gov (United States)

    Ward, Melissa; Norman, Haval; D'Souza, Manoranjan S

    2018-02-15

    Nicotine, an addictive component of tobacco smoke, produces both rewarding and aversive effects. Increasing the aversive effects of nicotine may help in promoting smoking cessation. However, neural targets mediating the aversive effects of nicotine have not been fully identified. In this study, we evaluated the role of kappa opioid receptors (KORs) in the aversive effects of nicotine (0.4 mg/kg, base; s.c.) using the nicotine-induced conditioned taste aversion (CTA) model in Wistar rats. The KORs were activated using the selective KOR agonist (±)U-50,488H (0, 0.03, 0.15 & 0.3mg/kg; s.c.) and inhibited using the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 15 & 30mg/kg; s.c.) in separate groups of rats using a between-subjects design. Pretreatment with the KOR agonist (±)U-50,488H (0.3mg/kg) significantly increased aversion for the nicotine-associated solution. Additionally, (±)U-50,488H (0.3mg/kg) on its own induced aversion to the flavored solution associated with it even in the absence of nicotine, suggesting that the KOR agonist induced increase in nicotine-induced aversion was an additive effect. Interestingly, administration of the KOR antagonist nor-BNI (30mg/kg) prior to conditioning with nicotine/saline, but not after conditioning with nicotine/saline, attenuated nicotine-induced aversive effects compared to saline controls. Taken together, these data suggest a role for KORs in the aversive effects of nicotine. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-01-30

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

  1. Efficacy of selected complementary and alternative medicine interventions for chronic pain.

    Science.gov (United States)

    Tan, Gabriel; Craine, Michael H; Bair, Matthew J; Garcia, M Kay; Giordano, James; Jensen, Mark P; McDonald, Shelley M; Patterson, David; Sherman, Richard A; Williams, Wright; Tsao, Jennie C I

    2007-01-01

    Complementary and alternative medicine (CAM) is a group of diverse medical and healthcare systems, therapies, and products that are not presently considered part of conventional medicine. This article provides an up-to-date review of the efficacy of selected CAM modalities in the management of chronic pain. Findings are presented according to the classification system developed by the National Institutes of Health National Center for Complementary and Alternative Medicine (formerly Office of Alternative Medicine) and are grouped into four domains: biologically based medicine, energy medicine, manipulative and body-based medicine, and mind-body medicine. Homeopathy and acupuncture are discussed separately as "whole or professionalized CAM practices." Based on the guidelines of the Clinical Psychology Division of the American Psychological Association, findings indicate that some CAM modalities have a solid track record of efficacy, whereas others are promising but require additional research. The article concludes with recommendations to pain practitioners.

  2. 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

  3. Long-term exposure to nicotine markedly reduces kynurenic acid in rat brain - In vitro and ex vivo evidence

    International Nuclear Information System (INIS)

    Zielinska, Elzbieta; Kuc, Damian; Zgrajka, Wojciech; Turski, Waldemar A.; Dekundy, Andrzej

    2009-01-01

    Kynurenic acid (KYNA) is a recognized broad-spectrum antagonist of excitatory amino acid receptors with a particularly high affinity for the glycine co-agonist site of the N-methyl-D-aspartate (NMDA) receptor complex. KYNA is also a putative endogenous neuroprotectant. Recent studies show that KYNA strongly blocks α7 subtype of nicotinic acetylcholine receptors (nAChRs). The present studies were aimed at assessing effects of acute and chronic nicotine exposure on KYNA production in rat brain slices in vitro and ex vivo. In brain slices, nicotine significantly increased KYNA formation at 10 mM but not at 1 or 5 mM. Different nAChR antagonists (dihydro-β-erythroidine, methyllycaconitine and mecamylamine) failed to block the influence exerted by nicotine on KYNA synthesis in cortical slices in vitro. Effects of acute (1 mg/kg, i.p.), subchronic (10-day) and chronic (30-day) administration of nicotine in drinking water (100 μg/ml) on KYNA brain content were evaluated ex vivo. Acute treatment with nicotine (1 mg/kg i.p.) did not affect KYNA level in rat brain. The subchronic exposure to nicotine in drinking water significantly increased KYNA by 43%, while chronic exposure to nicotine resulted in a reduction in KYNA by 47%. Co-administration of mecamylamine with nicotine in drinking water for 30 days reversed the effect exerted by nicotine on KYNA concentration in the cerebral cortex. The present results provide evidence for the hypothesis of reciprocal interaction between the nicotinic cholinergic system and the kynurenine pathway in the brain.

  4. Associations between selected allergens, phthalates, nicotine, polycyclic aromatic hydrocarbons, and bedroom ventilation and clinically confirmed asthma, rhinoconjunctivitis, and atopic dermatitis in preschool children

    DEFF Research Database (Denmark)

    Callesen, M.; Bekö, Gabriel; Weschler, Charles J.

    2014-01-01

    participating families. A single physician conducted clinical examinations of all 500 children. Children from the initially random control group with clinically confirmed allergic disease were subsequently excluded from the control group and admitted in the case group, leaving 242 in the healthy control group...... and clinically confirmed asthma, rhinoconjunctivitis, and atopic dermatitis. The study is a cross-sectional case-control study of 500 children aged 3-5years from Odense, Denmark. The 200 cases had at least two parentally reported allergic diseases, while the 300 controls were randomly selected from 2835...

  5. Contribution of adrenal hormones to nicotine-induced inhibition of synovial plasma extravasation in the rat.

    Science.gov (United States)

    Miao, F J; Benowitz, N L; Heller, P H; Levine, J D

    1997-01-01

    1. In this study, we examined the mechanism(s) by which s.c. nicotine inhibits synovial plasma extravasation. We found that nicotine dose-dependently inhibited bradykinin (BK)- and platelet activating factor (PAF)-induced plasma extravasation. 2. The effect of nicotine on both BK- and PAF-induced plasma extravasation was attenuated by adrenal medullectomy. ICI-118,551 (a selective beta 2-adrenoceptor blocker) (30 micrograms ml-1, intra-articularly) significantly attenuated the inhibitory action of high-dose (1 mg kg-1) nicotine on BK-induced plasma extravasation without affecting the inhibition by low- (0.01 microgram kg-1) dose nicotine or that on PAF-induced plasma extravasation by nicotine at any dose. This suggested that beta 2-adrenoceptors mediate the inhibitory actions of high-dose, but not low-dose, nicotine. We also found that systemic naloxone (an opioid receptor antagonist) (two hourly injections of 1 mg kg-1, i.p.) attenuated the inhibitory action produced by all doses of nicotine on BK- or PAF-induced plasma extravasation, suggesting the contribution of endogenous opioids. 3. RU-38,486 (a glucocorticoid receptor antagonist) (30 mg kg-1, s.c.), and metyrapone (a glucocorticoid synthesis inhibitor) (two hourly injections of 100 mg kg-1, i.p.) both attenuated the action of high-dose nicotine without affecting that of low-dose nicotine. 4. Spinal mecamylamine (a nicotinic receptor antagonist) (0.025 mg kg-1, intrathecally, i.t.) attenuated the action of high-dose, but not low-dose, nicotine, suggesting that part of the action of high-dose nicotine is mediated by spinal nicotinic receptors. 5. Combined treatment with ICI-118,551, naloxone and RU-38,486 attenuated the action of low-dose nicotine by an amount similar to that produced by naloxone alone but produced significantly greater attenuation of the effect of high-dose nicotine when compared to the action of any of the three antagonists alone.

  6. Patients with chronic insomnia have selective impairments in memory that are modulated by cortisol.

    Science.gov (United States)

    Chen, Gui-Hai; Xia, Lan; Wang, Fang; Li, Xue-Wei; Jiao, Chuan-An

    2016-10-01

    Memory impairment is a frequent complaint in insomniacs; however, it is not consistently demonstrated. It is unknown whether memory impairment in insomniacs involves neuroendocrine dysfunction. The participants in this study were selected from the clinical setting and included 21 patients with chronic insomnia disorder (CID), 25 patients with insomnia and comorbid depressive disorder (CDD), and 20 control participants without insomnia. We evaluated spatial working and reference memory, object working and reference memory, and object recognition memory using the Nine Box Maze Test. We also evaluated serum neuroendocrine hormone levels. Compared to the controls, the CID patients made significantly more errors in spatial working and object recognition memory (p memory types (p memory (r = .534, p = .033) and negatively correlated with the errors in object recognition memory (r = -.659, p = .006) in the CID patients. The results suggest that the CID patients had selective memory impairment, which may be mediated by increased cortisol levels. © 2016 Society for Psychophysiological Research.

  7. Chronic effects of fluoxetine, a selective inhibitor of serotonin uptake, on neurotransmitter receptors

    International Nuclear Information System (INIS)

    Wong, D.T.; Reid, L.R.; Bymaster, F.P.; Threlkeld, P.G.

    1985-01-01

    Fluoxetine administration to rats dose of 10mg/kg i.p. daily up to 12 or 24 days failed to change the concentration-dependent binding of [ 3 H]WB4101, [ 3 H]clonidine and [ 3 H]dihydroalprenolol to α 1 -, α 2 - and β-adrenergic receptors, respectively; [ 3 H]quinuclidinyl benzilate to muscarinic receptors; [ 3 H]pyrilamine to histamine H 1 receptors and [ 3 H]naloxone to opiate receptors. Persistent and significant decreases in receptor number (Bsub(max) value) without changes in the dissociation constant (Ksub(D) value) of [ 3 H]5-HT binding in cortical membranes were observed upon chronic treatment with fluoxetine administered either by intraperitoneal injection or incorporation in the diet. A detectable reduction of 5-HT 1 receptor number occured after once-daily injections of fluoxetine at 10mg/kg i.p. within 49 hours. After pretreatment for 3 days with p-chlorophenylalanine, an inhibitor of 5-HT synthesis, followed by repeated administration of fluoxetine, 5-HT 1 receptor numbers were higher than those of normal rats, suggesting a dependence on synaptic concentration of 5-HT for fluoxetine to affect a receptor down-regulation. These studies provide further evidence for the selectivity of fluoxetine as an inhibitor of 5-HT reuptake, resulting in a selective down-regulation of 5-HT 1 receptors in the cerebal cortex of rat brain. (Author)

  8. Efficacy of Selected Electrical Therapies on Chronic Low Back Pain: A Comparative Clinical Pilot Study.

    Science.gov (United States)

    Rajfur, Joanna; Pasternok, Małgorzata; Rajfur, Katarzyna; Walewicz, Karolina; Fras, Beata; Bolach, Bartosz; Dymarek, Robert; Rosinczuk, Joanna; Halski, Tomasz; Taradaj, Jakub

    2017-01-07

    BACKGROUND In the currently available research publications on electrical therapy of low back pain, generally no control groups or detailed randomization were used, and such studies were often conducted with relatively small groups of patients, based solely on subjective questionnaires and pain assessment scales (lacking measurement methods to objectify the therapeutic progress). The available literature also lacks a comprehensive and large-scale clinical study. The purpose of this study was to assess the effects of treating low back pain using selected electrotherapy methods. The study assesses the influence of individual electrotherapeutic treatments on reduction of pain, improvement of the range of movement in lower section of the spine, and improvement of motor functions and mobility. MATERIAL AND METHODS The 127 patients qualified for the therapy (ultimately, 123 patients completed the study) and assigned to 6 comparison groups: A - conventional TENS, B - acupuncture-like TENS, C - high-voltage electrical stimulation, D - interferential current stimulation, E - diadynamic current, and F - control group. RESULTS The research showed that using electrical stimulation with interferential current penetrating deeper into the tissues results in a significant and more efficient elimination of pain, and an improvement of functional ability of patients suffering from low back pain on the basis of an analysis of both subjective and objective parameters. The TENS currents and high voltage were helpful, but not as effective. The use of diadynamic currents appears to be useless. CONCLUSIONS Selected electrical therapies (interferential current, TENS, and high voltage) appear to be effective in treating chronic low back pain.

  9. 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.

  10. Intraclonal Cell Expansion and Selection Driven by B Cell Receptor in Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Colombo, Monica; Cutrona, Giovanna; Reverberi, Daniele; Fabris, Sonia; Neri, Antonino; Fabbi, Marina; Quintana, Giovanni; Quarta, Giovanni; Ghiotto, Fabio; Fais, Franco; Ferrarini, Manlio

    2011-01-01

    The mutational status of the immunoglobulin heavy-chain variable region (IGHV) genes utilized by chronic lymphocytic leukemia (CLL) clones defines two disease subgroups. Patients with unmutated IGHV have a more aggressive disease and a worse outcome than patients with cells having somatic IGHV gene mutations. Moreover, up to 30% of the unmutated CLL clones exhibit very similar or identical B cell receptors (BcR), often encoded by the same IG genes. These “stereotyped” BcRs have been classified into defined subsets. The presence of an IGHV gene somatic mutation and the utilization of a skewed gene repertoire compared with normal B cells together with the expression of stereotyped receptors by unmutated CLL clones may indicate stimulation/selection by antigenic epitopes. This antigenic stimulation may occur prior to or during neoplastic transformation, but it is unknown whether this stimulation/selection continues after leukemogenesis has ceased. In this study, we focused on seven CLL cases with stereotyped BcR Subset #8 found among a cohort of 700 patients; in six, the cells expressed IgG and utilized IGHV4-39 and IGKV1-39/IGKV1D-39 genes, as reported for Subset #8 BcR. One case exhibited special features, including expression of IgM or IgG by different subclones consequent to an isotype switch, allelic inclusion at the IGH locus in the IgM-expressing cells and a particular pattern of cytogenetic lesions. Collectively, the data indicate a process of antigenic stimulation/selection of the fully transformed CLL cells leading to the expansion of the Subset #8 IgG-bearing subclone. PMID:21541442

  11. Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    J. Donate-Correa

    2014-01-01

    Full Text Available Paricalcitol, a selective vitamin D receptor (VDR activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD, has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m2 and an intact parathyroid hormone (PTH level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P<0.01, TNF-α (11.9%, P=0.01, and IL-6 (7%, P<0.05, with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P=0.01 and 35.4% (P=0.01, respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.

  12. Selective modulation of Wnt ligands and their receptors in adipose tissue by chronic hyperadiponectinemia.

    Directory of Open Access Journals (Sweden)

    Nobuhiko Wada

    Full Text Available BACKGROUND: Adiponectin-transgenic mice had many small adipocytes in both subcutaneous and visceral adipose tissues, and showed higher sensitivity to insulin, longer life span, and reduced chronic inflammation. We hypothesized that adiponectin regulates Wnt signaling in adipocytes and thereby modulates adipocyte proliferation and chronic inflammation in adipose tissue. MATERIALS AND METHODS: We examined the expression of all Wnt ligands and their receptors and the activity of Wnt signaling pathways in visceral adipose tissue from wild-type mice and two lines of adiponectin-transgenic mice. The effects of adiponectin were also investigated in cultured 3T3-L1 cells. RESULTS: The Wnt5b, Wnt6, Frizzled 6 (Fzd6, and Fzd9 genes were up-regulated in both lines of transgenic mice, whereas Wnt1, Wnt2, Wnt5a, Wnt9b, Wnt10b, Wnt11, Fzd1, Fzd2, Fzd4, Fzd7, and the Fzd coreceptor low-density-lipoprotein receptor-related protein 6 (Lrp6 were reduced. There was no difference in total β-catenin levels in whole-cell extracts, non-phospho-β-catenin levels in nuclear extracts, or mRNA levels of β-catenin target genes, indicating that hyperadiponectinemia did not affect canonical Wnt signaling. In contrast, phosphorylated calcium/calmodulin-dependent kinase II (p-CaMKII and phosphorylated Jun N-terminal kinase (p-JNK were markedly reduced in adipose tissue from the transgenic mice. The adipose tissue of the transgenic mice consisted of many small cells and had increased expression of adiponectin, whereas cyclooxygenase-2 expression was reduced. Wnt5b expression was elevated in preadipocytes of the transgenic mice and decreased in diet-induced obese mice, suggesting a role in adipocyte differentiation. Some Wnt genes, Fzd genes, and p-CaMKII protein were down-regulated in 3T3-L1 cells cultured with a high concentration of adiponectin. CONCLUSION: Chronic hyperadiponectinemia selectively modulated the expression of Wnt ligands, Fzd receptors and LRP coreceptors

  13. 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....

  14. The health system burden of chronic disease care: an estimation of provider costs of selected chronic diseases in Uganda.

    Science.gov (United States)

    Settumba, Stella Nalukwago; Sweeney, Sedona; Seeley, Janet; Biraro, Samuel; Mutungi, Gerald; Munderi, Paula; Grosskurth, Heiner; Vassall, Anna

    2015-06-01

    To explore the chronic disease services in Uganda: their level of utilisation, the total service costs and unit costs per visit. Full financial and economic cost data were collected from 12 facilities in two districts, from the provider's perspective. A combination of ingredients-based and step-down allocation costing approaches was used. The diseases under study were diabetes, hypertension, chronic obstructive pulmonary disease (COPD), epilepsy and HIV infection. Data were collected through a review of facility records, direct observation and structured interviews with health workers. Provision of chronic care services was concentrated at higher-level facilities. Excluding drugs, the total costs for NCD care fell below 2% of total facility costs. Unit costs per visit varied widely, both across different levels of the health system, and between facilities of the same level. This variability was driven by differences in clinical and drug prescribing practices. Most patients reported directly to higher-level facilities, bypassing nearby peripheral facilities. NCD services in Uganda are underfunded particularly at peripheral facilities. There is a need to estimate the budget impact of improving NCD care and to standardise treatment guidelines. © 2015 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  15. 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)

  16. Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium

    NARCIS (Netherlands)

    Gribble, P.A.; Delahunt, E.; Bleakley, C.M.; Caulfield, B.; Docherty, C.L.; Fong, D.T.; Fourchet, F.; Hertel, J.; Hiller, C.E.; Kaminski, T.W.; McKeon, P.O.; Refshauge, K.M.; Wees, P.J. van der; Vicenzino, W.; Wikstrom, E.A.

    2014-01-01

    While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant or patient selection criteria across studies presents a potential obstacle to addressing the problem

  17. Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium

    NARCIS (Netherlands)

    Gribble, P.A.; Delahunt, E.; Bleakley, C.; Caulfield, B.; Docherty, C.; Fourchet, F.; Fong, D.T.; Hertel, J.; Hiller, C.; Kaminski, T.; McKeon, P.; Refshauge, K.; Wees, P.J. van der; Vincenzino, B.; Wikstrom, E.

    2014-01-01

    While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly.

  18. Spinal fusion for chronic low back pain: systematic review on the accuracy of tests for patient selection

    NARCIS (Netherlands)

    Willems, P.C.P.H.; Staal, J.B.; Walenkamp, G.H.; Bie, R.A. de

    2013-01-01

    BACKGROUND CONTEXT: Spinal fusion is a common but controversial treatment for chronic low back pain (LBP) with outcomes similar to those of programmed conservative care. To improve the results of fusion, tests for patient selection are used in clinical practice. PURPOSE: To determine the prognostic

  19. Selective attention towards painful faces among chronic pain patients: evidence from a modified version of the dot-probe.

    Science.gov (United States)

    Khatibi, Ali; Dehghani, Mohsen; Sharpe, Louise; Asmundson, Gordon J G; Pouretemad, Hamidreza

    2009-03-01

    Evidence that patients with chronic pain selectively attend to pain-related stimuli presented in modified Stroop and dot-probe paradigms is mixed. The pain-related stimuli used in these studies have been primarily verbal in nature (i.e., words depicting themes of pain). The purpose of the present study was to determine whether patients with chronic pain, relative to healthy controls, show selective attention for pictures depicting painful faces. To do so, 170 patients with chronic pain and 40 age- and education-matched healthy control participants were tested using a dot-probe task in which painful, happy, and neutral facial expressions were presented. Selective attention was denoted using the mean reaction time and the bias index. Results indicated that, while both groups shifted attention away from happy faces (and towards neutral faces), only the control group shifted attention away from painful faces. Additional analyses were conducted on chronic pain participants after dividing them into groups on the basis of fear of pain/(re)injury. The results of these analyses revealed that while chronic pain patients with high and low levels of fear both shifted attention away from happy faces, those with low fear shifted attention away from painful faces, whereas those with high fear shifted attention towards painful faces. These results suggest that patients with chronic pain selectively attend to facial expressions of pain and, importantly, that the tendency to shift attention towards such stimuli is positively influenced by high fear of pain/(re)injury. Implications of the findings and future research directions are discussed.

  20. Cellular, Molecular, and Genetic Substrates Underlying the Impact of Nicotine on Learning

    Science.gov (United States)

    Gould, Thomas J.; Leach, Prescott T.

    2013-01-01

    Addiction is a chronic disorder marked by long-lasting maladaptive changes in behavior and in reward system function. However, the factors that contribute to the behavioral and biological changes that occur with addiction are complex and go beyond reward. Addiction involves changes in cognitive control and the development of disruptive drug-stimuli associations that can drive behavior. A reason for the strong influence drugs of abuse can exert on cognition may be the striking overlap between the neurobiological substrates of addiction and of learning and memory, especially areas involved in declarative memory. Declarative memories are critically involved in the formation of autobiographical memories, and the ability of drugs of abuse to alter these memories could be particularly detrimental. A key structure in this memory system is the hippocampus, which is critically involved in binding multimodal stimuli together to form complex long-term memories. While all drugs of abuse can alter hippocampal function, this review focuses on nicotine. Addiction to tobacco products is insidious, with the majority of smokers wanting to quit; yet the majority of those that attempt to quit fail. Nicotine addiction is associated with the presence of drug-context and drug-cue associations that trigger drug seeking behavior and altered cognition during periods of abstinence, which contributes to relapse. This suggests that understanding the effects of nicotine on learning and memory will advance understanding and potentially facilitate treating nicotine addiction. The following sections examine: 1) how the effects of nicotine on hippocampus-dependent learning change as nicotine administration transitions from acute to chronic and then to withdrawal from chronic treatment and the potential impact of these changes on addiction, 2) how nicotine usurps the cellular mechanisms of synaptic plasticity, 3) the physiological changes in the hippocampus that may contribute to nicotine withdrawal

  1. 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.

  2. Effects of transdermally administered nicotine on aspects of attention, task load, and mood in women and men.

    Science.gov (United States)

    Trimmel, Michael; Wittberger, Susanne

    2004-07-01

    This double-blind placebo-controlled study was conducted to determine nicotine effects on diverse types of attentional performance, task load, and mood considering sex effects as suggested by animal studies. Twelve smokers, 12 deprived smokers and 12 nonsmokers (6 females, 6 males in each group) were investigated. Participants were treated either by 5 mg/16 h nicotine patches (Nicorette) or placebo. Effects of treatment were examined by a computerized attention-test battery; mood was assessed by the Berliner-Alltagssprachliches-Stimmungs-Inventar and task load by the NASA Task Load Index (NASA-TLX). Results showed that nicotine significantly increased the number of hits and decreased reaction time (RT) in the vigilance task. In the selective attention task combined with irrelevant speech as background noise, nicotine enhanced rate of hits. Although it was indicated that nicotine leads to a generally higher accuracy in attention tasks, response time of visual search was prolonged, contradicting a universal facilitation by nicotine. Participants experienced mental demand and temporal demand lower and rated alertness higher when in the nicotine condition. These effects were independent of smoking status, indicating "true" nicotine effects. Females took significant advantage of nicotine in the vigilance task, reaching the performance level of males, accompanied by a higher rated alertness. Results indicate task- and sex-dependent nicotine effects.

  3. 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.

  4. Smoking, nicotine and psychiatric disorders: evidence for therapeutic role, controversies and implications for future research.

    Science.gov (United States)

    Dursun, S M; Kutcher, S

    1999-02-01

    Researchers interested in investigating the possible therapeutic effects and the mechanisms of action of nicotine in neuropsychiatric disorders face a social-scientific-ethical dilemma. This dilemma comprises three components: (1) the known addictive potential of nicotine makes careful evaluation of the therapeutic potential of this compound socially unattractive; (2) the potential misuse of scientifically determined data by the tobacco 'lobby' creates ethical concerns; and (3) the possible confusion between the differential effects of nicotine in human smokers versus non-smokers creates difficulties in study designs in voluntary human subjects. Therefore, it is imperative that, at the onset of this review, the authors stress that they do not advocate cigarette-smoking as a route of nicotine intake under any circumstances on the basis that controlled dosing of nicotine may be of potential benefit in some neuropsychiatric disorders. In this article, we review the psychopharmacology of nicotine and its effects in a variety of neuropsychiatric disorders including schizophrenia, depression, anxiety and Tourette's syndrome. Possible mechanisms of action of nicotine directly or indirectly via its interaction with other neurotransmitter systems (i.e. serotonin, dopamine and noradrenaline) in relation to its potential role in these disorders are discussed. It is postulated that new drugs may need to be developed that selectively interact with nicotinic receptors without addiction potential.

  5. Nicotine improves obesity and hepatic steatosis and ER stress in diet-induced obese male rats.

    Science.gov (United States)

    Seoane-Collazo, Patricia; Martínez de Morentin, Pablo B; Fernø, Johan; Diéguez, Carlos; Nogueiras, Rubén; López, Miguel

    2014-05-01

    Nicotine, the main addictive component of tobacco, promotes body weight reduction in humans and rodents. Recent evidence has suggested that nicotine acts in the central nervous system to modulate energy balance. Specifically, nicotine modulates hypothalamic AMP-activated protein kinase to decrease feeding and to increase brown adipose tissue thermogenesis through the sympathetic nervous system, leading to weight loss. Of note, most of this evidence has been obtained in animal models fed with normal diet or low-fat diet (LFD). However, its effectiveness in obese models remains elusive. Because obesity causes resistance towards many factors involved in energy homeostasis, the aim of this study has been to compare the effect of nicotine in a diet-induced obese (DIO) model, namely rats fed a high-fat diet, with rats fed a LFD. Our data show that chronic peripheral nicotine treatment reduced body weight by decreasing food intake and increasing brown adipose tissue thermogenesis in both LFD and DIO rats. This overall negative energy balance was associated to decreased activation of hypothalamic AMP-activated protein kinase in both models. Furthermore, nicotine improved serum lipid profile, decreased insulin serum levels, as well as reduced steatosis, inflammation, and endoplasmic reticulum stress in the liver of DIO rats but not in LFD rats. Overall, this evidence suggests that nicotine diminishes body weight and improves metabolic disorders linked to DIO and might offer a clear-cut strategy to develop new therapeutic approaches against obesity and its metabolic complications.

  6. 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...

  7. A non-selective (amitriptyline), but not a selective (citalopram), serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache.

    OpenAIRE

    Bendtsen, L; Jensen, R; Olesen, J

    1996-01-01

    OBJECTIVES: Although the tricyclic antidepressant amitriptyline is extensively used in the prophylactic treatment of chronic tension-type headache, only few studies have investigated the efficacy of this treatment and the results are contradictory. In addition, the new selective serotonin reuptake inhibiting antidepressants, which are widely used in depression and of potential value in pain management, have never been investigated in a placebo controlled study of tension-type headache. The ai...

  8. The 5-HT2C receptor agonist lorcaserin reduces nicotine self-administration, discrimination, and reinstatement: relationship to feeding behavior and impulse control.

    Science.gov (United States)

    Higgins, Guy A; Silenieks, Leo B; Rossmann, Anne; Rizos, Zoe; Noble, Kevin; Soko, Ashlie D; Fletcher, Paul J

    2012-04-01

    Lorcaserin ((1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl) is a selective 5-HT(2C) receptor agonist with clinical efficacy in phase-III obesity trials. Based on evidence that this drug class also affects behaviors motivated by drug reinforcement, we compared the effect of lorcaserin on behavior maintained by food and nicotine reinforcement, as well as the stimulant and discriminative stimulus properties of nicotine in the rat. Acutely administered lorcaserin (0.3-3 mg/kg, subcutaneous (SC)) dose dependently reduced feeding induced by 22-h food deprivation or palatability. Effects up to 1 mg/kg were consistent with a specific effect on feeding motivation. Lorcaserin (0.6-1 mg/kg, SC) reduced operant responding for food on progressive and fixed ratio schedules of reinforcement. In this dose range lorcaserin also reversed the motor stimulant effect of nicotine, reduced intravenous self-administration of nicotine, and attenuated the nicotine cue in rats trained to discriminate nicotine from saline. Lorcaserin also reduced the reinstatement of nicotine-seeking behavior elicited by a compound cue comprising a nicotine prime and conditioned stimulus previously paired with nicotine reinforcement. Lorcaserin did not reinstate nicotine-seeking behavior or substitute for a nicotine cue. Finally, lorcaserin (0.3-1 mg/kg) reduced nicotine-induced increases in anticipatory responding, a measure of impulsive action, in rats performing the five-choice serial reaction time task. Importantly, these results indicate that lorcaserin, and likely other selective 5-HT(2C) receptor agonists, similarly affect both food- and nicotine-motivated behaviors, and nicotine-induced impulsivity. Collectively, these findings highlight a therapeutic potential for 5-HT(2C) agonists such as lorcaserin beyond obesity into addictive behaviors, such as nicotine dependence.

  9. 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.

  10. 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

  11. Protective Effect of Nicotine on Sepsis-Induced Oxidative Multiorgan Damage: Role of Neutrophils.

    Science.gov (United States)

    Özdemir-Kumral, Zarife N; Özbeyli, Dilek; Özdemir, Ahmet F; Karaaslan, Bugra M; Kaytaz, Kübra; Kara, Mustafa F; Tok, Olgu E; Ercan, Feriha; Yegen, Berrak Ç

    2017-07-01

    Despite its adverse health consequences, tobacco smoking is associated with lower incidence of several neurodegenerative and inflammatory diseases. The present study is aimed to show the effects of nicotine, major tobacco constituent, on five organs targeted by sepsis. Male Wistar albino rats received tap water with (5mg/kg) or without nicotine for 14 days. Under ketamine anesthesia, sepsis (n = 50) was induced by ligation and puncture of the cecum, while sham group (n = 8) had only laparotomy. In other rats, nicotine drink was withdrawn for 5 days before sepsis induction, while in acute nicotine group, rats were injected with nicotine (30mg/kg, i.p.) before sepsis, but had no oral intake. Rats were decapitated 24 hours after surgery to obtain lung, liver, ileum, heart, and kidney tissues to determine malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) activities. Data were analyzed by one-way analysis of variance and Tukey multiple comparison tests or Student's t test. Chronic nicotine administration or its withdrawal reduced lipid peroxidation and MPO activity and prevented GSH depletion with some varying results in different target tissues. Nicotine injection prior to sepsis depressed MPO activity in all tissues and reduced MDA levels except for the lung, while GSH levels were elevated only in the hepatic and ileal tissues. Histologically observed injury was ameliorated by all nicotine treatments at varying degrees. The findings of the present study indicate that long-term nicotine administration reduces sepsis-induced oxidative damage in several tissues, which appears to involve inhibition of neutrophil activity in the inflamed tissues. Nicotine administration or its withdrawal reduced lipid peroxidation and neutrophil content and prevented GSH depletion with some varying results in different target tissues. A single injection prior to sepsis induction depressed MPO activity in all the tissues and reduced all tissue MDA levels except

  12. Single center experience in selecting the laparoscopic Frey procedure for chronic pancreatitis.

    Science.gov (United States)

    Tan, Chun-Lu; Zhang, Hao; Li, Ke-Zhou

    2015-11-28

    To share our experience regarding the laparoscopic Frey procedure for chronic pancreatitis (CP) and patient selection. All consecutive patients undergoing duodenum-preserving pancreatic head resection from July 2013 to July 2014 were reviewed and those undergoing the Frey procedure for CP were included in this study. Data on age, gender, body mass index (BMI), American Society of Anesthesiologists score, imaging findings, inflammatory index (white blood cells, interleukin (IL)-6, and C-reaction protein), visual analogue score score during hospitalization and outpatient visit, history of CP, operative time, estimated blood loss, and postoperative data (postoperative mortality and morbidity, postoperative length of hospital stay) were obtained for patients undergoing laparoscopic surgery. The open surgery cases in this study were analyzed for risk factors related to extensive bleeding, which was the major reason for conversion during the laparoscopic procedure. Age, gender, etiology, imaging findings, amylase level, complications due to pancreatitis, functional insufficiency, and history of CP were assessed in these patients. Nine laparoscopic and 37 open Frey procedures were analyzed. Of the 46 patients, 39 were male (85%) and seven were female (16%). The etiology of CP was alcohol in 32 patients (70%) and idiopathic in 14 patients (30%). Stones were found in 38 patients (83%). An inflammatory mass was found in five patients (11%). The time from diagnosis of CP to the Frey procedure was 39 ± 19 (9-85) mo. The BMI of patients in the laparoscopic group was 20.4 ± 1.7 (17.8-22.4) kg/m(2) and was 20.6 ± 2.9 (15.4-27.7) kg/m(2) in the open group. All patients required analgesic medication for abdominal pain. Frequent acute pancreatitis or severe abdominal pain due to acute exacerbation occurred in 20 patients (43%). Pre-operative complications due to pancreatitis were observed in 18 patients (39%). Pancreatic functional insufficiency was observed in 14 patients (30

  13. Chronic exposure to sublethal doses of radiation mimetic ZeocinTM selects for clones deficient in homologous recombination

    International Nuclear Information System (INIS)

    Delacote, Fabien; Deriano, Ludovic; Lambert, Sarah; Bertrand, Pascale; Saintigny, Yannick; Lopez, Bernard S.

    2007-01-01

    DNA double-strand breaks (DSBs) are highly toxic lesions leading to genome variability/instability. The balance between homologous recombination (HR) and non-homologous end-joining (NHEJ), two alternative DSB repair systems, is essential to ensure genome maintenance in mammalian cells. Here, we transfected CHO hamster cells with the pcDNA TM 3.1/Zeo plasmid, and selected transfectants with Zeocin TM , a bleomycin analog which produces DSBs. Despite the presence of a Zeocin TM resistance gene in pcDNA TM 3.1/Zeo, Zeocin TM induced 8-10 γ-H2AX foci per cell. This shows that the Zeocin TM resistance gene failed to fully detoxify cells treated with Zeocin TM , and that during selection cells were submitted to a chronic sublethal DSB stress. Selected clones show decreases in both spontaneous and induced intrachromosomal HR. In contrast, in an in vitro assay, these clones show an increase in NHEJ products specific to the KU86 pathway. We selected cells, in the absence of pcDNA TM 3.1/Zeo, with low and sublethal doses of Zeocin TM , producing a mean 8-10 γ-H2AX foci per cell. Newly selected clones exhibited similar phenotypes: HR decrease accompanied by an increase in KU86-dependent NHEJ efficiency. Thus chronic exposure to sublethal numbers of DSBs selects cells whose HR versus NHEJ balance is altered. This may well have implications for radio- and chemotherapy, and for management of environmental hazards

  14. Stability and selectivity of a chronic, multi-contact cuff electrode for sensory stimulation in human amputees.

    Science.gov (United States)

    Tan, Daniel W; Schiefer, Matthew A; Keith, Michael W; Anderson, J Robert; Tyler, Dustin J

    2015-04-01

    Stability and selectivity are important when restoring long-term, functional sensory feedback in individuals with limb-loss. Our objective is to demonstrate a chronic, clinical neural stimulation system for providing selective sensory response in two upper-limb amputees. Multi-contact cuff electrodes were implanted in the median, ulnar, and radial nerves of the upper-limb. Nerve stimulation produced a selective sensory response on 19 of 20 contacts and 16 of 16 contacts in subjects 1 and 2, respectively. Stimulation elicited multiple, distinct percept areas on the phantom and residual limb. Consistent threshold, impedance, and percept areas have demonstrated that the neural interface is stable for the duration of this on-going, chronic study. We have achieved selective nerve response from multi-contact cuff electrodes by demonstrating characteristic percept areas and thresholds for each contact. Selective sensory response remains consistent in two upper-limb amputees for 1 and 2 years, the longest multi-contact sensory feedback system to date. Our approach demonstrates selectivity and stability can be achieved through an extraneural interface, which can provide sensory feedback to amputees.

  15. 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.

  16. A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Holmskov, Uffe; Sørensen, Signe Bek

    2017-01-01

    Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro...

  17. A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Holmskov, Uffe; Sørensen, Signe Bek

    2017-01-01

    Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro...

  18. Chronic cannabis use and ERP correlates of visual selective attention during the performance of a flanker go/nogo task.

    Science.gov (United States)

    Nicholls, Clare; Bruno, Raimondo; Matthews, Allison

    2015-09-01

    The aim of the study was to investigate the relationship between chronic cannabis use and visual selective attention by examining event-related potentials (ERPs) during the performance of a flanker go/nogo task. Male participants were 15 chronic cannabis users (minimum two years use, at least once per week) and 15 drug naive controls. Cannabis users showed longer reaction times compared to controls with equivalent accuracy. Cannabis users also showed a reduction in the N2 'nogo effect' at frontal sites, particularly for incongruent stimuli, and particularly in the right hemisphere. This suggests differences between chronic cannabis users and controls in terms of inhibitory processing within the executive control network, and may implicate the right inferior frontal cortex. There was also preliminary evidence for differences in early selective attention, with controls but not cannabis users showing modulation of N1 amplitude by flanker congruency. Further investigation is required to examine the potential reversibility of these residual effects after long-term abstinence and to examine the role of early selective attention mechanisms in more detail. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. 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

  20. Neural Signatures of Cognitive Flexibility and Reward Sensitivity Following Nicotinic Receptor Stimulation in Dependent Smokers: A Randomized Trial.

    Science.gov (United States)

    Lesage, Elise; Aronson, Sarah E; Sutherland, Matthew T; Ross, Thomas J; Salmeron, Betty Jo; Stein, Elliot A

    2017-06-01

    . Similarly, decreased mesocorticolimbic activity associated with cognitive flexibility in abstinent smokers was restored to the level of nonsmokers following stimulation of nicotinic acetylcholine receptors (familywise error-corrected P < .05). Conversely, neural signatures of decreased reward sensitivity in smokers (vs nonsmokers; familywise error-corrected P < .05) in the dorsal striatum and anterior cingulate cortex were not mitigated by nicotine or varenicline. There was a double dissociation between the effects of chronic nicotine dependence on neural representations of reward sensitivity and acute effects of stimulation of nicotinic acetylcholine receptors on behavioral and neural signatures of cognitive flexibility in smokers. These chronic and acute pharmacologic effects were observed in overlapping mesocorticolimbic regions, suggesting that available pharmacotherapies may alleviate deficits in the same circuitry for certain mental computations but not for others. clinicaltrials.gov Identifier: NCT00830739.

  1. 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.

  2. Mecamylamine, dihydro-β-erythroidine, and dextromethorphan block conditioned responding evoked by the conditional stimulus effects of nicotine

    Science.gov (United States)

    Struthers, Amanda M.; Wilkinson, Jamie L.; Dwoskin, Linda P.; Crooks, Peter A.; Bevins, Rick A.

    2009-01-01

    Current smokers express the desire to quit. However, the majority find it difficult to remain abstinent. As such, research efforts continually seek to develop more effective treatment. One such area of research involves the interoceptive stimulus effects of nicotine as either a discriminative stimulus in an operant drug discrimination task, or more recently as a conditional stimulus (CS) in a discriminated goal-tracking task. The present work investigated the potential role nicotinic acetylcholine receptors in the CS effects of nicotine (0.4 mg/kg) using antagonists with differential selectivity for β2*, α7*, α6β2*, and α3β4* receptors. Methyllycaconitine (MLA) had no effect on nicotine-evoked conditioned responding. Mecamylamine and dihydro-β-erythroidine (DHβE) dose dependently blocked responding evoked by the nicotine CS. In a time-course assessment of mecamylamine and DHβE, each blocked conditioned responding when given 5 min before testing and still blocked conditioned responding when administered 200 min before testing. Two novel bis-picolinium analogs (N, N’-(3, 3′-(dodecan-1,12-diyl)-bis-picolinium dibromide [bPiDDB], and N, N’-(decan-1,10-diyl)-bis-picolinium diiodide [bPiDI]) did not block nicotine-evoked conditioned responding. Finally, pretreatment with low dose combinations of mecamylamine, dextromethorphan, and/or bupropion were used to target α3β4* receptors. No combination blocked conditioned responding evoked by the training dose of nicotine. However, a combination of mecamylamine and dextromethorphan partially blocked nicotine-evoked conditioned responding to a lower dose of nicotine (0.1 mg/kg). These results indicate that β2* and potentially α3β4* nicotinic acetylcholine receptors play a role in the CS effects of nicotine and are potential targets for the development of nicotine cessation aids. PMID:19778551

  3. Retrograde approach for the recanalization of coronary chronic total occlusion: collateral selection and collateral related complication.

    Science.gov (United States)

    Ma, Jian-Ying; Qian, Ju-Ying; Ge, Lei; Fan, Bing; Wang, Qi-Bing; Yan, Yan; Zhang, Feng; Yao, Kang; Huang, Dong; Ge, Jun-Bo

    2013-03-01

    The retrograde approach through collaterals has been applied in the treatment of chronic total occlusion (CTO) lesions during percutaneous recanalization of coronary arteries. This study was to investigate the success rate of recanalization and collateral related complications in patients when using the retrograde approach. Eighty-four cases subjected to retrograde approach identified from July 2005 to July 2012 were included in this study. Patient characteristics, procedural outcomes and in-hospital clinical events were evaluated. Mean age of the patient was (59.6 ± 11.2) years old and 91.7% were men. The target CTO lesions were distributed among the left anterior descending artery in 45 cases (53.5%), left circumflex artery in one case (1.2%), right coronary artery in 34 cases (40.5%), and left main in four cases (4.8%). The overall success rate of recanalization was 79.8%. The septal collateral was three times more frequently used for retrograde access than the epicardial collateral, 68/84 (81%) vs. 16/84 (19%). Successful wire passage through the collateral channel was achieved in 58 (72.6%) patients. The success rate of recanalization was 93.1% (54/58) in patients with and 50% (13/26) in patients without successful retrograde wire passage of the collateral channel (P collaterals was achieved in 49 of 68 septal collaterals (72.1%) and in 9 of 16 epicardial collaterals (56.3%) (P = NS). There was no significant difference between the septal collateral group and the epicardial group in the success rate of recanalization after retrograde wire crossing the collaterals (91.8% vs. 100%, P > 0.05). CART or reverse CART technique was used in 15 patients, and 14 patients (93.3%) were recanalized successfully. Collateral related perforation occurred in three (18.8%) cases with the epicardial collateral as the first choice (compared with the septal collateral group (0), P collaterals. The retrograde approach is an effective technique to recanalize CTO lesions, the septal

  4. A review of the relationship between leg power and selected chronic disease in older adults

    DEFF Research Database (Denmark)

    Strollo, S. E.; Caserotti, Paolo; Ward, R. E.

    2015-01-01

    characterized. Importantly, individuals with these conditions have shown improved leg power with training. METHODS: A search was performed using PubMed to identify original studies published in English from January 1998 to August 2013. Leg power studies, among older adults ≥ 50 years of age, which assessed......OBJECTIVE: This review investigates the relationship between leg muscle power and the chronic conditions of osteoarthritis, diabetes mellitus, and cardiovascular disease among older adults. Current literature assessing the impact of chronic disease on leg power has not yet been comprehensively......), diabetes mellitus (n=5), and cardiovascular disease (n=6). Studies generally supported associations of lower leg power among older adults with chronic disease, although small sample sizes, cross-sectional data, homogenous populations, varied disease definitions, and inconsistent leg power methods limited...

  5. Nicotine enhances proliferation, migration, and radioresistance of human malignant glioma cells through EGFR activation

    International Nuclear Information System (INIS)

    Khalil, A.A.; Jameson, M.J.; Broaddus, W.C.; Lin, P.S.; Chung, T.D.

    2013-01-01

    It has been suggested that continued tobacco use during radiation therapy contributes to maintenance of neoplastic growth despite treatment with radiation. Nicotine is a cigarette component that is an established risk factor for many diseases, neoplastic and otherwise. The hypothesis of this work is that nicotine promotes the proliferation, migration, and radioresistance of human malignant glioma cells. The effect of nicotine on cellular proliferation, migration, signaling, and radiation sensitivity were evaluated for malignant glioma U87 and GBM12 cells by use of the AlamarBlue, scratch healing, and clonogenic survival assays. Signal transduction was assessed by immunoblotting for activated EGFR, extracellular regulated kinase (ERK), and AKT. At concentrations comparable with those found in chronic smokers, nicotine induced malignant glioma cell migration, growth, colony formation, and radioresistance. Nicotine increased phosphorylation of EGFR tyr992 , AKT ser473 , and ERK. These molecular effects were reduced by pharmacological inhibitors of EGFR, PI3K, and MEK. It was therefore concluded that nicotine stimulates the malignant behavior of glioma cells in vitro by activation of the EGFR and downstream AKT and ERK pathways. (author)

  6. Using eye movements to investigate selective attention in chronic daily headache.

    Science.gov (United States)

    Liossi, Christina; Schoth, Daniel E; Godwin, Hayward J; Liversedge, Simon P

    2014-03-01

    Previous research has demonstrated that chronic pain is associated with biased processing of pain-related information. Most studies have examined this bias by measuring response latencies. The present study extended previous work by recording eye movement behaviour in individuals with chronic headache and in healthy controls while participants viewed a set of images (i.e., facial expressions) from 4 emotion categories (pain, angry, happy, neutral). Biases in initial orienting were assessed from the location of the initial shift in gaze, and biases in the maintenance of attention were assessed from the duration of gaze on the picture that was initially fixated, and the mean number of visits, and mean fixation duration per image category. The eye movement behaviour of the participants in the chronic headache group was characterised by a bias in initial shift of orienting to pain. There was no evidence of individuals with chronic headache visiting more often, or spending significantly more time viewing, pain images compared to other images. Both participant groups showed a significantly greater bias to maintain gaze longer on happy images, relative to pain, angry, and neutral images. Results are consistent with a pain-related bias that operates in the orienting of attention on pain-related stimuli, and suggest that chronic pain participants' attentional biases for pain-related information are evident even when other emotional stimuli are present. Pain-related information-processing biases appear to be a robust feature of chronic pain and may have an important role in the maintenance of the disorder. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  7. Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

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

    2018-05-01

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

  9. Will chronic e-cigarette use cause lung disease?

    OpenAIRE

    Rowell, Temperance R.; Tarran, Robert

    2015-01-01

    Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig ...

  10. Autoradiographic localization of putative nicotinic receptors in the rat brain using 125I-neuronal bungarotoxin

    International Nuclear Information System (INIS)

    Schulz, D.W.; Loring, R.H.; Aizenman, E.; Zigmond, R.E.

    1991-01-01

    Neuronal bungarotoxin (NBT), a snake venom neurotoxin, selectively blocks nicotinic receptors in many peripheral and central neuronal preparations. alpha-Bungarotoxin (alpha BT), on the other hand, a second toxin isolated from the venom of the same snake, is an ineffective nicotinic antagonist in most vertebrate neuronal preparations studied thus far. To examine central nicotinic receptors recognized by NBT, we have characterized the binding of 125I-labeled NBT (125I-NBT) to rat brain membranes and have mapped the distribution of 125I-NBT binding in brain sections using quantitative light microscopic autoradiography. The binding of 125I-NBT was found to be saturable, of high affinity, and heterogeneously distributed in the brain. Pharmacological studies suggested that more than one population of sites is labeled by 125I-NBT. For example, one component of 125I-NBT binding was also recognized by alpha BT, while a second component, not recognized by alpha BT, was recognized by the nicotinic agonist nicotine. The highest densities of these alpha BT-insensitive, nicotine-sensitive sites were found in the fasciculus retroflexus, the lateral geniculate nucleus, the medial terminal nucleus of the accessory optic tract, and the olivary pretectal nucleus. alpha BT-sensitive NBT binding sites were found in highest density in the lateral geniculate nucleus, the subthalamic nucleus, the dorsal tegmental nucleus, and the medial mammillary nucleus (lateral part). The number of brain regions with a high density of 125I-NBT binding sites, blocked either by alpha BT or by nicotine, is low when compared with results obtained using other approaches to studying the central distribution of nicotinic receptors, such as labeling with 3H-nicotine or labeling with cDNA probes to mRNAs coding for putative receptor subunits

  11. Home noninvasive ventilatory support for patients with chronic obstructive pulmonary disease : patient selection and perspectives

    NARCIS (Netherlands)

    Storre, Jan Hendrik; Callegari, Jens; Magnet, Friederike Sophie; Schwarz, Sarah Bettina; Duiverman, Marieke Leontine; Wijkstra, Peter Jan; Windisch, Wolfram

    2018-01-01

    Long-term or home mechanical noninvasive ventilation (Home-NIV) has become a well-established form of therapy over the last few decades for chronic hypercapnic COPD patients in European countries. However, meta-analyses and clinical guidelines do not recommend Home-NIV for COPD patients on a routine

  12. Children born by women with rheumatoid arthritis have increased susceptibility for selected chronic diseases – a nationwide cohort study

    DEFF Research Database (Denmark)

    Jølving, Line Riis; Nielsen, Jan; Kesmodel, Ulrik Schiøler

    2018-01-01

    OBJECTIVE: Fetal exposure to maternal rheumatoid arthritis (RA) might impact the long-term risk of disease in the offspring. We examined a possible association between maternal RA and 15 selected groups of chronic diseases in the offspring. METHODS: This nationwide cohort study was based...... used, taking a large range of confounders into consideration, computing the Hazard Ratios (HR) of child- and adolescence diseases. RESULTS: In children being exposed to maternal RA in utero, the HR's of thyroid diseases was 2.19 (95% CI, 1.14 - 4.21), epilepsy 1.61 (95% CI, 1.16 - 2.25), and RA 2.......89 (95% CI, 2.06 - 4.05). The HR's for anxiety and personality disorders and chronic lung disease including asthma were in the range of 1.15 - 1.16, but these were not statistically significant. CONCLUSIONS: Our results suggest that in utero exposure to maternal RA is associated with an increased risk...

  13. 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...

  14. 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.

  15. Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex

    DEFF Research Database (Denmark)

    Wichern, Franziska; Jensen, Majbrit M; Christensen, Ditte Z

    2017-01-01

    The nicotinic acetylcholine receptor (nAChR) regulator chaperone (NACHO) was recently identified as an important regulator of nAChR maturation and surface expression. Here we show that NACHO levels decrease during early postnatal development in rats. This decrease occurs earlier and to a greater...... degree in the frontal cortex (FC) compared with the hippocampus (HIP). We further show that rats exposed to nicotine during pre- and postnatal development exhibit significantly higher NACHO levels in the FC at postnatal day (PND) 21, but not at PND60. Repeated exposure to nicotine selectively during...... a single exposure to a combination of nicotine and the type II α7 nAChR positive allosteric modulator (PAM) PNU-120596, but not the type I PAM AVL-3288. These findings suggest that exposure to nAChR agonism affects NACHO protein levels, and that this effect is more pronounced during pre- or early postnatal...

  16. Tanezumab: a selective humanized mAb for chronic lower back pain

    Directory of Open Access Journals (Sweden)

    Webb MP

    2018-02-01

    Full Text Available Michael P Webb,1 Erik M Helander,2 Bethany L Menard,2 Richard D Urman,3 Alan D Kaye2 1Department of Anesthesiology, North Shore Hospital, Auckland, New Zealand; 2Department of Anesthesiology, LSU School of Medicine, New Orleans, LA, USA; 3Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Chronic lower back pain is a significant disease that affects nearly 20% of the worldwide population. Along with hindering patients’ quality of life, chronic lower back pain is considered to be the second most common cause of disability among Americans. Treating chronic lower back pain is often a challenge for providers, especially in light of our current opioid epidemic. With this epidemic and an increased aging population, there is an imminent need for development of new pharmacologic therapeutic options, which are not only effective but also pose minimal adverse effects to the patient. With these considerations, a novel therapeutic agent called tanezumab has been developed and studied. Tanezumab is a humanized monoclonal immunoglobulin G2 antibody that works by inhibiting the binding of NGF to its receptors. NGF is involved in the function of sensory neurons and fibers involved in nociceptive transduction. It is commonly seen in excess in inflammatory joint conditions and in chronic pain patients. Nociceptors are dependent on NGF for growth and ongoing function. The inhibition of NGF binding to its receptors is a mechanism by which pain pathways can be interrupted. In this article, a number of recent randomized controlled trials are examined relating to the efficacy and safety of tanezumab in the treatment of chronic lower back pain. Although tanezumab was shown to be an effective pain modulator in major trials, several adverse effects were seen among different doses of the medication, one of which led to a clinical hold placed by the US Food and Drug

  17. 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

  18. 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

  19. 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

  20. Select tissue mineralconcentrations and chronic wasting disease status in mule deer from north-central Colorado

    OpenAIRE

    Wolfe, Lisa L.; Conner, Mary M.; Bedwell, Cathy L.; Lukacs, Paul M.; Miller, Michael W.

    2010-01-01

    Trace mineral imbalances have been suggested as having a causative or contributory role in chronic wasting disease (CWD), a prion disease of several North American cervid species. To begin exploring relationships between tissue mineral concentrations and CWD in natural systems, we measured liver tissue concentrations of copper, manganese, and molybdenum in samples from 447 apparently healthy, adult (≥2 yr old) mule deer (Odocoileus hemionus) culled or vehicle killed from free-ranging populati...

  1. Immunolocalization of androgen and oestrogen receptors in the ventral lobe of rat (Rattus norvegicus) prostate after long-term treatment with ethanol and nicotine.

    Science.gov (United States)

    Fávaro, W J; Cagnon, V H A

    2008-12-01

    Nicotine and alcohol adversely affect prostate gland function. In this work, immunohistochemistry was used to investigate the immunoreactivity and distribution of androgen and alpha, beta-oestrogen receptors following chronic treatment with alcohol, nicotine or a combination of both substances, as well as to relate these results to the development of possible prostatic pathologies. Forty male rats were divided into four groups: the Control group received tap water; the Alcoholic group received diluted 10% Gay Lussac ethanol; the Nicotine group received a 0.125 mg/100 g body weight dose of nicotine injected subcutaneously on a daily basis (Sigma Chemical Company, St. Louis, MO, USA); the Nicotine-Alcohol group received simultaneous alcohol and nicotine treatment. After 90 days of treatment, samples of the ventral lobe of the prostate were collected and processed for immunohistochemistry, light microscopy and the quantification of serum hormonal concentrations. The results showed significantly decreased serum testosterone levels and increased serum oestrogen levels in the animals from the nicotine-alcohol, the alcoholic and the nicotine groups, as well as their hormonal receptor levels. Then, it was concluded that ethanol and nicotine compromised the prostatic hormonal balance, which is a crucial factor to maintain the morphological and physiological features of this organ.

  2. CHRNA3 genotype, nicotine dependence, lung function and disease in the general population

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Nordestgaard, Børge G; Bojesen, Stig E

    2012-01-01

    The CHRNA3 rs1051730 polymorphism has been associated to chronic obstructive pulmonary disease (COPD), lung cancer and nicotine dependence in case-control studies with high smoking exposure; however, its influence on lung function and COPD severity in the general population is largely unknown. We...... genotyped 57,657 adult individuals from the Copenhagen General Population Study, of whom 34,592 were ever-smokers. Information on spirometry, hospital admissions, smoking behaviour and use of nicotinic replacement therapy was recorded. In homozygous (11%), heterozygous (44%) and noncarrier (45%) ever...

  3. Studies of Nicotinic Receptors in Non-human Primates Using PET and SPECT

    International Nuclear Information System (INIS)

    Kassiou, M.; University of Sydney,

    2002-01-01

    reduced to the level of the cerebellum in both displacement and pre-treatment experiments using cytisine. This clearly demonstrates the specificity and saturability of [ 76 Br]bromoepibatidine binding to nAChRs. In a baboon that had been treated with MPTP the uptake of [ 76 Br]bromoepibatidine, when compared to the control animal, was reduced in the thalamus by 50% while the radioactivity in the striatum and cortices was similar to that of the cerebellum. These results suggest that [ 76 Br]bromoepibatidine has the potential to be a useful radioligand for studying the pharmacology of nAChRs. Nicotinic acetylcholine receptors are shown to be increased in cortex, cerebellum, hippocampus and thalamus homogenates of autopsied brain samples from smokers. A positive correlation between cigarette consumption and nAChR increase has been identified, indicating dose dependent increase. Smokers who had stopped smoking at least 2 months before death had nAChR levels similar to those of non-smokers. In an attempt to visualise and quantify in vivo nAChR upregulation the subtype selective radioligand 5-[ 123 I]iodo-A85380 was used with SPECT an kinetic modelling. In order to induce nAChR upregulation a male papio hamadryas baboon was chronically treated with nicotine (2 mg/kg/24h) for 14 days by subcutaneous implantation of an osmotic pump. Blood samples where taken during the dosing period to determine the amount of nicotine in plasma. A SPECT study was performed prior to nicotine dosing to obtain baseline levels of 5- [ 123 I]iodo-A85380 uptake. When imaging was performed while nicotine was still found in plasma resulted in an inhibition study. Seven days following removal of the osmotic pump resulted in increased 5-[ 123 I]iodo-A85380 in thalamus, cortex and cerebellum, while images obtained 4 weeks later indicated some recovery and levels returning back close to baseline. This clearly demonstrates in vivo nAChR upregulation with 5-[ 123 I]iodo-A85380 and quantitative dynamic SPECT

  4. Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites

    Directory of Open Access Journals (Sweden)

    Darin J. Knapp

    2016-07-01

    . Overall, these effects are complex in terms of their neuroimmune targets and neuroanatomical specificity. Further investigation of the differential distribution of cytokine induction across neuroanatomical regions, individual cell types (e.g., neuronal phenotypes and glia, severity of chronic alcohol exposure, as well as across differing stress types may prove useful in understanding differential mechanisms of induction and for targeting select systems for pharmacotherapeutic intervention in alcoholism.

  5. 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.

  6. 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

  7. Chronic toxicity of selected polycyclic aromatic hydrocarbons to algae and crustaceans using passive dosing.

    Science.gov (United States)

    Bragin, Gail E; Parkerton, Thomas F; Redman, Aaron D; Letinksi, Daniel J; Butler, Josh D; Paumen, Miriam Leon; Sutherland, Cary A; Knarr, Tricia M; Comber, Mike; den Haan, Klaas

    2016-12-01

    Because of the large number of possible aromatic hydrocarbon structures, predictive toxicity models are needed to support substance hazard and risk assessments. Calibration and evaluation of such models requires toxicity data with well-defined exposures. The present study has applied a passive dosing method to generate reliable chronic effects data for 8 polycyclic aromatic hydrocarbons (PAHs) on the green algae Pseudokirchneriella subcapitata and the crustacean Ceriodaphnia dubia. The observed toxicity of these substances on algal growth rate and neonate production were then compared with available literature toxicity data for these species, as well as target lipid model and chemical activity-based model predictions. The use of passive dosing provided well-controlled exposures that yielded more consistent data sets than attained by past literature studies. Results from the present study, which were designed to exclude the complicating influence of ultraviolet light, were found to be well described by both target lipid model and chemical activity effect models. The present study also found that the lack of chronic effects for high molecular weight PAHs was consistent with the limited chemical activity that could be achieved for these compounds in the aqueous test media. Findings from this analysis highlight that variability in past literature toxicity data for PAHs may be complicated by both poorly controlled exposures and photochemical processes that can modulate both exposure and toxicity. Environ Toxicol Chem 2016;35:2948-2957. © 2016 SETAC. © 2016 SETAC.

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. 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 ...

  14. 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.

  15. Rewarding and aversive effects of nicotine are segregated within the nucleus accumbens.

    Science.gov (United States)

    Sellings, Laurie H L; Baharnouri, Golriz; McQuade, Lindsey E; Clarke, Paul B S

    2008-07-01

    Forebrain dopamine plays a critical role in motivated behavior. According to the classic view, mesolimbic dopamine selectively guides behavior motivated by positive reinforcers. However, this has been challenged in favor of a wider role encompassing aversively motivated behavior. This controversy is particularly striking in the case of nicotine, with opposing claims that either the rewarding or the aversive effect of nicotine is critically dependent on mesolimbic dopamine transmission. In the present study, the effects of 6-hydroxydopamine lesions of nucleus accumbens core vs. medial shell on intravenous nicotine conditioned place preference and conditioned taste aversion were examined in male adult rats. Dopaminergic denervation in accumbens medial shell was associated with decreased nicotine conditioned place preference. Conversely, denervation in accumbens core was associated with an increase in conditioned place preference. In addition, dopaminergic denervation of accumbens core but not medial shell abolished conditioned taste aversion for nicotine. We conclude that nucleus accumbens core and medial shell dopaminergic innervation exert segregated effects on rewarding and aversive effects of nicotine. More generally, our findings indicate that dopaminergic transmission may mediate or enable opposing motivational processes within functionally distinct domains of the accumbens.

  16. Erythrina mulungu alkaloids are potent inhibitors of neuronal nicotinic receptor currents in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Pedro Setti-Perdigão

    Full Text Available Crude extracts and three isolated alkaloids from Erythrina mulungu plants have shown anxiolytic effects in different animal models. We investigated whether these alkaloids could affect nicotinic acetylcholine receptors and if they are selective for different central nervous system (CNS subtypes. Screening experiments were performed using a single concentration of the alkaloid co-applied with acetylcholine in whole cell patch-clamp recordings in three different cell models: (i PC12 cells natively expressing α3* nicotinic acetylcholine receptors; (ii cultured hippocampal neurons natively expressing α7* nicotinic acetylcholine receptors; and (iii HEK 293 cells heterologoulsy expressing α4β2 nicotinic acetylcholine receptors. For all three receptors, the percent inhibition of acetylcholine-activated currents by (+-11á-hydroxyerysotrine was the lowest, whereas (+-erythravine and (+-11á-hydroxyerythravine inhibited the currents to a greater extent. For the latter two substances, we obtained concentration-response curves with a pre-application protocol for the α7* and α4β2 nicotinic acetylcholine receptors. The IC50 obtained with (+-erythravine and (+-11á-hydroxyerythravine were 6 µM and 5 µM for the α7* receptors, and 13 nM and 4 nM for the α4β2 receptors, respectively. Our data suggest that these Erythrina alkaloids may exert their behavioral effects through inhibition of CNS nicotinic acetylcholine receptors, particularly the α4β2 subtype.

  17. Cyclic voltammetric response of nicotinic acid and nicotinamide on a polycrystalline gold electrode

    International Nuclear Information System (INIS)

    Wang Xiaoxia; Yang Nianjun; Wan Qijin

    2006-01-01

    The oxidation of nicotinic acid and nicotinamide on a polycrystalline gold electrode occurred at almost same potentials but their reduction did at different peak potentials. The redox reaction mechanisms of nicotinic acid and nicotinamide were rationalized by the formation/disappearance of the new nitrogen-oxygen bonds in the pyridine rings by means of cyclic voltammetry and bulk electrolysis. The anodic currents of nicotinic acid and nicotinamide were controlled by diffusion, while the cathodic ones by adsorption. The difference in the cathodic peak potentials of nicotinic acid and nicotinamide on the polycrystalline gold electrode is attributed to the effect of the electron densities of remote substituents on the pyridine rings. The cathodic peak currents at about 0.20 V were linear with their concentrations in the range of 2.4 mM to 2.7 μM and 2.4 mM to 3.3 μM with detection limits of 0.27 and 0.33 μM for nicotinic acid and nicotinamide, respectively. Voltammetry was then adopted for the selective monitoring the content of nicotinic acid and nicotinamide in pharmaceuticals

  18. A man before his time: Russell's insights into nicotine, smoking, treatment and curbing the smoking problem.

    Science.gov (United States)

    McNeill, Ann; Robson, Debbie

    2018-04-01

    This narrative review aimed to provide a brief overview of five key research 'classics' produced by the innovative and radical thought leader, Professor Michael Anthony Hamilton Russell (1932-2009), drawing upon his other work wherever feasible. Narrative review. From more than 250 publications, we selected papers we considered seminal texts, published in 1971, 1976, 1978, 1979 and 1991. Russell was among the first researchers to explain that smoking was a dependence disorder caused by the drug nicotine decades before this was recognized formally. He therefore saw quickly the importance of delivering nicotine in a less harmful format as a way of controlling nicotine withdrawal when stopping smoking, first studying nicotine gum. In addition to pharmacotherapies, Russell's research also explored the role of behavioural support, particularly the role of general practitioners (GPs), alone as well as supported by specialist clinics; this research underpinned initiatives in England to reimburse doctors for giving advice to smokers, and to provide a national network of smoking cessation services. Research on nicotine uptake from other delivery systems and routes led Russell to theorize that the speed and dose of delivery impacted upon the effectiveness of a product to act as a substitute for smoking. He commented on the addictiveness of the high nicotine boli delivered in quick succession when smoking cigarettes and argued that alternative recreational nicotine delivery systems would need to be promoted actively to smokers in order for them to compete with cigarettes, a forerunner for contemporary debates on electronic cigarettes. The legacy of Russell's landmark research is seen in present-day nicotine science, policy and discourse. © 2017 Society for the Study of Addiction.

  19. The nicotine + alcohol interoceptive drug state: contribution of the components and effects of varenicline in rats.

    Science.gov (United States)

    Randall, Patrick A; Cannady, Reginald; Besheer, Joyce

    2016-08-01

    Nicotine and alcohol co-use is highly prevalent, and as such, individuals experience the interoceptive effects of both substances together. Therefore, examining sensitivity to a compound nicotine and alcohol (N + A) interoceptive cue is critical to broaden our understanding of mechanisms that may contribute to nicotine and alcohol co-use. This work assessed the ability of a N + A interoceptive cue to gain control over goal-tracking behavior and determined the effects of the α4β2 nicotinic partial agonist and smoking cessation compound varenicline on sensitivity to N + A. Two groups of male Long Evans rats were trained to discriminate N + A (0.4 mg/kg nicotine + 1 g/kg alcohol, intragastric gavage (IG)) from water under two different training conditions using a Pavlovian drug discrimination task. The effects of varenicline (0, 1, 3 mg/kg, intraperitoneally (IP)) administered alone and on sensitivity to N + A and the components were determined. Under both training conditions, N + A rapidly gained control over behavior, with a greater contribution of nicotine to the N + A compound cue. Varenicline fully substituted for the N + A training dose, and varenicline (1 mg/kg) enhanced sensitivity to the lowest N + A dose (0.1 N + 0.1 A). Given the high selectivity of varenicline for the α4β2 receptor, this finding suggests a functional role for α4β2 nicotinic acetylcholine receptors (nAChRs) in modulating sensitivity to N + A. The N + A compound cue is a unique cue that is modulated, in part, by activity at the α4β2 nAChR. These findings advance understanding of the interoceptive effects of nicotine and alcohol in combination and may have implications in relation to their co-use.

  20. 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.

  1. A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Holmskov, Uffe; Sørensen, Signe Bek

    2017-01-01

    Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro......-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value...... to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including...

  2. Survey of health status, nutrition and geography of food selection of chronic liver disease patients.

    Science.gov (United States)

    Leslie, Timothy; Pawloski, Lisa; Kallman-Price, Jillian; Escheik, Carey; Hossain, Noreen; Fang, Yun; Gerber, Lynn H; Younossi, Zobair M

    2014-01-01

    Obesity, a complex disease determined both by genetic and environmental factors, is strongly associated with NAFLD, and has been demonstrated to have a negative impact on HCV and other chronic liver diseases (CLD). This study assessed the association between type and location of food sources and chronic liver disease (CLD) using Geographic Information Systems (GIS). CLD patients completed surveys [267 subjects, 56.5% female, age 55.8 ± 12.0, type of CLD: 36.5% hepatitis C (HCV), 19.9% hepatitis B (HBV), 19.9% non-alcoholic fatty liver disease (NAFLD); primary food source (PFS): 80.8% grocery store, secondary: 26.2% bulk food store, tertiary: 20.5% restaurants; fresh food (FF): 83%, pre-packaged (PP) 8.7%, already prepared (AP) 8.3%]. FF consumers had significantly fewer UEH servings/month (p = 0.030) and lived further away from convenience stores (1.69 vs. 0.95 km, p = 0.0001). Stepwise regression reveals the lowest FF consumers were NAFLD patients, subjects with UEH or restaurants and ethnic food stores as their PFS (R = 0.557, p = 0.0001). Eating already-packaged foods and utilizing restaurants or ethnic food stores as the PFS positively correlated with NAFLD (R = 0.546, p = 0.0001). Environmental food source measures, including type and density, should be included when examining areas hyper-saturated with a variety of food options. In hyper-saturated food environments, NAFLD patients consume more prepared food and less FF. CLD patients with UEH also eat significantly more prepared food and frequent restaurants and ethnic food stores as their PFS.

  3. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P Rats.

    Directory of Open Access Journals (Sweden)

    Jessica Godfrey

    Full Text Available Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total or were given access only to water (control. Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4-desaturase (Degs2, an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels

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

    Science.gov (United States)

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

    2014-07-01

    Few clinical studies involving cigarettes have provided a comprehensive picture of smoke exposure, test article characterization, and insights into sensory properties combined. The purpose of these pilot studies was to determine whether cigarettes with different levels of nicotine but similar tar levels would affect sensory experience or smoking behavior so as to significantly alter levels of selected biomarkers of exposure (BOE). In 2 confined, double-blind studies, 120 adult smokers switched from Marlboro Gold cigarettes at baseline to either 1 of 2 lower nicotine cigarettes or 1 of 2 higher nicotine cigarettes and then to the other cigarette after 5 days. Urinary excretion of exposure biomarkers (nicotine equivalents [NE], total and free 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL], 1-hydroxypyrene, and 3-hydroxypropyl mercapturic acid) as well as carboxyhemoglobin and plasma cotinine were measured at baseline, Day 5, and Day 10. Daily cigarette consumption was monitored and sensory characteristics were rated for each cigarette. With higher nicotine yield, urine NE, urine total NNAL, and plasma cotinine increased while nonnicotine BOE decreased without changes in cigarette consumption. In contrast, with lower nicotine yield, urine NE, urine total NNAL, and plasma cotinine dropped while nonnicotine BOE and cigarettes per day increased. Higher nicotine cigarettes were rated harsher and stronger than at baseline while lower nicotine cigarettes were less strong. All 4 test cigarettes were highly disliked. These studies demonstrate that abrupt increases or decreases in nicotine and the resulting sensory changes impact BOE through changes in intensity or frequency of smoking. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Nicotine-induced enhancement of attention in the five-choice serial reaction time task: the influence of task demands.

    Science.gov (United States)

    Hahn, B; Shoaib, M; Stolerman, I P

    2002-07-01

    Beneficial effects of nicotine on cognitive processes including attention have potential therapeutic uses and have been proposed as incentives for tobacco smoking. To establish task conditions under which the effects of nicotine on attention are obtained reliably and to characterise such effects further. Rats were trained in a modified version of the five-choice serial reaction time task (5-CSRTT) to detect 1-s light stimuli with greater than 70% accuracy and fewer than 20% omission errors. Nicotine was tested under different task requirements by varying signal event rate, stimulus duration and stimulus predictability, and by introducing white-noise distractors. Nicotine (0.05-0.2 mg/kg, s.c.) repeatedly improved accuracy and reduced omission errors and reaction times, leading to increases in numbers of reinforcers earned. Anticipatory responding was increased. Parametric modifications intended to increase demands on sustained attention did not affect performance in a manner suggesting that this subtype of attention was being taxed, and the effects of nicotine were not more marked under such conditions. Shorter stimulus durations impaired performance, but this manipulation weakened the effect of nicotine on accuracy. In contrast, the presence of noise distractors facilitated the effects of nicotine to the extent that distractor-induced impairments were abolished by the drug. The 5-CSRTT can provide a sensitive rodent model for the attention-enhancing effects of nicotine. Changes made to the procedure may have increased its sensitivity to nicotine, particularly with respect to accuracy. There were indications that the effects of nicotine were largest on processes of selective attention or on disengaging attention from irrelevant events and shifting it to behaviourally significant stimuli.

  6. Nicotinic acid receptor abnormalities in human skin cancer: implications for a role in epidermal differentiation.

    Directory of Open Access Journals (Sweden)

    Yira Bermudez

    Full Text Available Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through G(i-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells.Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional G(i-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional.The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s of nicotinic acid receptors in human skin homeostasis.

  7. 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.

  8. 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 ...

  9. 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

  10. PI3K/Akt-independent NOS/HO activation accounts for the facilitatory effect of nicotine on acetylcholine renal vasodilations: modulation by ovarian hormones.

    Directory of Open Access Journals (Sweden)

    Eman Y Gohar

    Full Text Available We investigated the effect of chronic nicotine on cholinergically-mediated renal vasodilations in female rats and its modulation by the nitric oxide synthase (NOS/heme oxygenase (HO pathways. Dose-vasodilatory response curves of acetylcholine (0.01-2.43 nmol were established in isolated phenylephrine-preconstricted perfused kidneys obtained from rats treated with or without nicotine (0.5-4.0 mg/kg/day, 2 weeks. Acetylcholine vasodilations were potentiated by low nicotine doses (0.5 and 1 mg/kg/day in contrast to no effect for higher doses (2 and 4 mg/kg/day. The facilitatory effect of nicotine was acetylcholine specific because it was not observed with other vasodilators such as 5'-N-ethylcarboxamidoadenosine (NECA, adenosine receptor agonist or papaverine. Increases in NOS and HO-1 activities appear to mediate the nicotine-evoked enhancement of acetylcholine vasodilation because the latter was compromised after pharmacologic inhibition of NOS (L-NAME or HO-1 (zinc protoporphyrin, ZnPP. The renal protein expression of phosphorylated Akt was not affected by nicotine. We also show that the presence of the two ovarian hormones is necessary for the nicotine augmentation of acetylcholine vasodilations to manifest because nicotine facilitation was lost in kidneys of ovariectomized (OVX and restored after combined, but not individual, supplementation with medroxyprogesterone acetate (MPA and estrogen (E2. Together, the data suggests that chronic nicotine potentiates acetylcholine renal vasodilation in female rats via, at least partly, Akt-independent HO-1 upregulation. The facilitatory effect of nicotine is dose dependent and requires the presence of the two ovarian hormones.

  11. Modulation of P-selection and platelet aggregation in chronic periodontitis: A clinical study

    Science.gov (United States)

    Perumal, Ramesh; Rajendran, Maheashwari; Krishnamurthy, Malathi; Ganji, Kiran Kumar; Pendor, Sunil Dattuji

    2014-01-01

    Background: The primary etiologic factor of periodontitis is the subgingival infection with a group of Gram negative pathogens. Transient bacteremia in periodontitis patients underlie chronic production and systemic increases of various proinflammatory mediators, including Interleukin (IL)-1α, IL-6, C-reactive protein and Tumor necrosis factor (TNF)-α. P- selectin is a member of selectin family of cell surface receptor which is located in the membrane of the secretory granules (alpha granules) of platelets and in the membrane of the Weibel-Palade bodies of the vascular endothelial cells. P selectin redistributes from the membrane of the granules to the plasma membrane when platelets and endothelial cells are activated and thus degranulated. Aim: To compare the level of platelet activation, soluble P Selectin level and morphological changes and aggregation of platelets in patients in periodontitis patients compared to healthy controls. Materials and Methods: 80 patients were included in the study with the age group of 35-60. The patients were divided into 2 groups, 40 subjects with generalized chronic periodontitis and 40 healthy subjects taken as control. Periodontal Examination using clinical parameters namely, Bleeding Index, Plaque Index, Probing Pocket Depth and Clinical Attachment Level were recorded. Collection of blood samples for estimation of serum soluble P- selectin level by ELISA method. Evaluation of Platelet morphology and grading the platelet aggregation. Results: P-selectin expression shows that the mean value for control group is 4.97 ± 16.56 ng/mL and study group 13.05 ± 29.94 ng/mL which was significantly higher than control group with P value 0.001. Platelet morphological changes shows small form – mean value for control group is 75.83% ± 14.24% while for study group is 39.08%. ± 21.59; Big form – mean value for control group 0.80% ± 0.35% while for study group 0.48% ± 1.3%and Spider form- mean value for control group 23.88% ± 14

  12. Is dependence on one drug associated with dependence on other drugs? The cases of alcohol, caffeine and nicotine.

    Science.gov (United States)

    Hughes, J R; Oliveto, A H; MacLaughlin, M

    2000-01-01

    Several studies have correlated the use of one drug with that of another drug; however, whether dependence on one drug is associated with dependence on another drug, independent of any use/use association, is unclear. We asked 196 randomly-selected subjects the DSM-IV criteria for dependence as applied to alcohol, caffeine, and nicotine. Among ever users, the severity of alcohol vs nicotine dependence and alcohol vs caffeine dependence was related, but this relationship was weak (r = .22 & .31). Nicotine and caffeine dependence were not correlated. These results fail to confirm theories of commonality that hypothesize dependence on one drug predisposes to dependence on another drug.

  13. Molecularly imprinted polymer beads for nicotine recognition prepared by RAFT precipitation polymerization: a step forward towards multifunctionalities

    DEFF Research Database (Denmark)

    Zhou, Tongchang; Jørgensen, Lars; Mattebjerg, Maria Ahlm

    2014-01-01

    A nicotine imprinted polymer was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using methacrylic acid (MAA) as a functional monomer. The resulting molecularly imprinted polymers were monodispersed beads with an average diameter of 1.55 mm. The molecular...... selectivity of the imprinted polymer beads was evaluated by studying the uptake of nicotine and its structural analogs by the polymer beads. Equilibrium binding results indicate that the amount of nicotine bound to the imprinted polymer beads is significantly higher than that bound to the nonimprinted polymer...

  14. Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium.

    Science.gov (United States)

    Gribble, Phillip A; Delahunt, Eamonn; Bleakley, Chris; Caulfield, Brian; Docherty, Carrie; Fourchet, François; Fong, Daniel Tik-Pui; Hertel, Jay; Hiller, Claire; Kaminski, Thomas; McKeon, Patrick; Refshauge, Kathryn; van der Wees, Philip; Vincenzino, Bill; Wikstrom, Erik

    2014-07-01

    While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Amygdala activation as a marker for selective attention toward neutral faces in a chronic traumatic brain injury population.

    Science.gov (United States)

    Young, Leanne R; Yu, Weikei; Holloway, Michael; Rodgers, Barry N; Chapman, Sandra B; Krawczyk, Daniel C

    2017-09-01

    There has been great interest in characterizing the response of the amygdala to emotional faces, especially in the context of social cognition. Although amygdala activation is most often associated with fearful or angry stimuli, there is considerable evidence that the response of the amygdala to neutral faces is both robust and reliable. This characteristic of amygdala function is of particular interest in the context of assessing populations with executive function deficits, such as traumatic brain injuries, which can be evaluated using fMRI attention modulation tasks that evaluate prefrontal control over representations, notably faces. The current study tested the hypothesis that the amygdala may serve as a marker of selective attention to neutral faces. Using fMRI, we gathered data within a chronic traumatic brain injury population. Blood Oxygenation Level Dependent (BOLD) signal change within the left and right amygdalae and fusiform face areas was measured while participants viewed neutral faces and scenes, under conditions requiring participants to (1) categorize pictures of faces and scenes, (2) selectively attend to either faces or scenes, or (3) attend to both faces and scenes. Findings revealed that the amygdala is an effective marker for selective attention to neutral faces and, furthermore, it was more face-specific than the fusiform face area. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The role of chronic physical exercise and selective attention at encoding on implicit and explicit memory.

    Science.gov (United States)

    Padilla, Concepción; Mayas, Julia; Ballesteros, Soledad; Andrés, Pilar

    2017-09-01

    Despite the evidence revealing benefits of chronic cardiovascular exercise on executive functions, little research has been conducted on long-term memory. We aimed to investigate the effect of physical exercise on implicit and explicit memory when attention was modulated at encoding in two groups of active and sedentary participants. With this purpose, attention was manipulated in a similar way in the implicit and explicit memory tasks by presenting picture outlines of two familiar objects, one in blue and the other in green, and participants were asked to pay attention only to one of them. Implicit memory was assessed through conceptual priming and explicit memory through a free recall task followed by recognition. The results did not reveal significant differences between groups in conceptual priming or free recall. However, in recognition, while both groups had similar discrimination for attended stimuli, active participants showed lower discrimination between unattended and new stimuli. These results suggested that exercise may have effects on specific cognitive processes, that is, that active participants may suppress non-relevant information better than sedentary participants, making the discrimination between unattended and new items more difficult.

  17. A hierarchical instrumental decision theory of nicotine dependence.

    Science.gov (United States)

    Hogarth, Lee; Troisi, Joseph R

    2015-01-01

    It is important to characterize the learning processes governing tobacco-seeking in order to understand how best to treat this behavior. Most drug learning theories have adopted a Pavlovian framework wherein the conditioned response is the main motivational process. We favor instead a hierarchical instrumental decision account, wherein expectations about the instrumental contingency between voluntary tobacco-seeking and the receipt of nicotine reward determines the probability of executing this behavior. To support this view, we review titration and nicotine discrimination research showing that internal signals for deprivation/satiation modulate expectations about the current incentive value of smoking, thereby modulating the propensity of this behavior. We also review research on cue-reactivity which has shown that external smoking cues modulate expectations about the probability of the tobacco-seeking response being effective, thereby modulating the propensity of this behavior. Economic decision theory is then considered to elucidate how expectations about the value and probability of response-nicotine contingency are integrated to form an overall utility estimate for that option for comparison with qualitatively different, nonsubstitute reinforcers, to determine response selection. As an applied test for this hierarchical instrumental decision framework, we consider how well it accounts for individual liability to smoking uptake and perseveration, pharmacotherapy, cue-extinction therapies, and plain packaging. We conclude that the hierarchical instrumental account is successful in reconciling this broad range of phenomenon precisely because it accepts that multiple diverse sources of internal and external information must be integrated to shape the decision to smoke.

  18. 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

  19. 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...

  20. 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).

  1. 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.

  2. Cognitive Performances Are Selectively Enhanced during Chronic Caloric Restriction or Resveratrol Supplementation in a Primate

    Science.gov (United States)

    Marchal, Julia; Picq, Jean-Luc; Aujard, Fabienne

    2011-01-01

    Effects of an 18-month treatment with a moderate, chronic caloric restriction (CR) or an oral supplementation with resveratrol (RSV), a potential CR mimetic, on cognitive and motor performances were studied in non-human primates, grey mouse lemurs (Microcebus murinus). Thirty-three adult male mouse lemurs were assigned to three different groups: a control (CTL) group fed ad libitum, a CR group fed 70% of the CTL caloric intake, and an RSV group (RSV supplementation of 200 mg.kg−1.day−1) fed ad libitum. Three different cognitive tests, two motor tests, one emotional test and an analysis of cortisol level were performed in each group. Compared to CTL animals, CR or RSV animals did not show any change in motor performances evaluated by rotarod and jump tests, but an increase in spontaneous locomotor activity was observed in both groups. Working memory was improved by both treatments in the spontaneous alternation task. Despite a trend for CR group, only RSV supplementation increased spatial memory performances in the circular platform task. Finally, none of these treatments induced additional stress to the animals as reflected by similar results in the open field test and cortisol analyses compared to CTL animals. The present data provided the earliest evidence for a beneficial effect of CR or RSV supplementation on specific cognitive functions in a primate. Taken together, these results suggest that RSV could be a good candidate to mimic long-term CR effects and support the growing evidences that nutritional interventions can have beneficial effects on brain functions even in adults. PMID:21304942

  3. Knowledge about inhaler use among the chronic asthma patients in selected hospitals.

    Science.gov (United States)

    Parvin, I A; Ahmad, S A; Islam, M N

    2011-08-01

    This cross sectional descriptive study was conducted among the chronic asthma patients attending three Institutes of Dhaka city namely National Asthma Center, The National Institute of Diseases of Chest and Hospital (NIDCH), Mohakhali, and Dhaka Medical College Hospital to assess the level of knowledge regarding inhaler use. Convenient sampling was adopted. Data were collected using one semi-structured questionnaire through face-to-face interview. The patients were aged from 18 to 75 years with mean age being 40.68 years and sd +/- 11.659 years. The mean monthly income of the respondents found was 8278.52 taka with standard deviation +/- 3523.315 taka. Mean duration of bronchial asthma was 9.44 years with sd +/- 4.862 years. Out of the total 298 respondents 103(35.8%) possessed "excellent knowledge" on inhalers. Ninety one (31.6%) had "adequate knowledge", sixty nine (24.0%) had "poor knowledge" and thirty five (8.7%) respondents were found having "no knowledge" about inhalers. Males were seen having better knowledge than the females (chi2 =66.582, df=3, pknowledge than those from the outdoors (pLevel of Knowledge was also found to be associated with the educational status of the respondents. Respondents with higher education possessed more than the respondents with lower education (p<0.001). Though most of the physicians now prescribe inhalers, but many of them do not explain the proper use of inhaler. This may be corrected through training and motivation of physicians at Medical Colleges and Hospitals and during various medical conferences and other programs. To reduce the extent of suffering and economic burden of asthma patients and their families, active education program for the patients and training program for the health care providers, regarding "inhaler use technique" demands early consideration.

  4. The transition to modernity and chronic disease: mismatch and natural selection.

    Science.gov (United States)

    Corbett, Stephen; Courtiol, Alexandre; Lummaa, Virpi; Moorad, Jacob; Stearns, Stephen

    2018-05-09

    The Industrial Revolution and the accompanying nutritional, epidemiological and demographic transitions have profoundly changed human ecology and biology, leading to major shifts in life history traits, which include age and size at maturity, age-specific fertility and lifespan. Mismatch between past adaptations and the current environment means that gene variants linked to higher fitness in the past may now, through antagonistic pleiotropic effects, predispose post-transition populations to non-communicable diseases, such as Alzheimer disease, cancer and coronary artery disease. Increasing evidence suggests that the transition to modernity has also altered the direction and intensity of natural selection acting on many traits, with important implications for public and global health.

  5. Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal LPS exposure: a study in rats

    Directory of Open Access Journals (Sweden)

    Uta Waterhouse

    2016-10-01

    Full Text Available Maternal exposure to infectious agents is a predisposing factor for schizophrenia with associated cognitive deficits in offspring. A high incidence of smoking in these individuals in adulthood might be, at least in part, due to the cognitive-enhancing effects of nicotine. Here, we have used prenatal exposure to maternal lipopolysaccharide (LPS, bacterial endotoxin at different time points as a model for cognitive deficits in schizophrenia to determine whether nicotine reverses any associated impairments. Pregnant rats were treated subcutaneously with LPS (0.5 mg/kg at one of three neurodevelopmental time periods [gestation days (GD 10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early adulthood [postnatal day (PND 60] and included: prepulse inhibition (PPI, latent inhibition (LI and delayed non-matching to sample (DNMTS. Following PND 100, daily nicotine injections (0.6 mg/kg, subcutaneously were administered, and animals were re-tested in the same tasks (PND 110. Only maternal LPS exposure early during fetal neurodevelopment (GD 10-11 resulted in deficits in all tests compared to animals that had been prenatally exposed to saline at the same gestational time point. Repeated nicotine treatment led to global (PPI and selective (LI improvements in performance. Early but not later prenatal LPS exposure induced consistent deficits in cognitive tests with relevance for schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention (LI and induced a global enhancement of sensorimotor gating (PPI.

  6. Assessment of chronic thromboembolic pulmonary hypertension by three-dimensional contrast-enhanced MR angiography - comparison with selective intraarterial DSA

    International Nuclear Information System (INIS)

    Kreitner, K.F.; Ley, S.; Kauczor, H.U.; Kalden, P.; Pitton, M.B.; Thelen, M.; Mayer, E.; Laub, G.

    2000-01-01

    Purpose: This study compares contrast-enhanced 3D-MR angiography (MRA) of the pulmonary arteries with selective intraarterial DSA in patients with chronic thromboembolic pulmonary hypertension. Materials and methods: 20 patients preoperatively underwent a contrast-enhanced 3D-MRA of the pulmonary arteries at 1.5 T using the phased-array body coil. For MRA, we used a 3D-Flash-sequence after bolus timing. 2 radiologists analyzed the acquired image material in consensus with respect to the detection of central thromboembolic material and the visualization of the pulmonary arterial tree. Finally, the MR angiograms were compared with selective DSA images using surgical findings as the definitive standard. Results: MRA demonstrated central thromboembolic material, vessel cut-offs and abnormal proximal-to-distal tapering in all patients. Compared to DSA, MRA depicted the pulmonary vessels up to the segmental level in all cases, it was inferior to DSA in delineation of the subsegmental arteries (sensitivity 87%, specificity 100%). The central beginning of the thromboembolic occlusions seen at MRA corresponded to the beginning of the deobliteration procedure during pulmonary thromboendarterectomy in every case. (orig.) [de

  7. Ethacrynic acid exhibits selective toxicity to chronic lymphocytic leukemia cells by inhibition of the Wnt/beta-catenin pathway.

    Directory of Open Access Journals (Sweden)

    Desheng Lu

    Full Text Available BACKGROUND: Aberrant activation of Wnt/beta-catenin signaling promotes the development of several cancers. It has been demonstrated that the Wnt signaling pathway is activated in chronic lymphocytic leukemia (CLL cells, and that uncontrolled Wnt/beta-catenin signaling may contribute to the defect in apoptosis that characterizes this malignancy. Thus, the Wnt signaling pathway is an attractive candidate for developing targeted therapies for CLL. METHODOLOGY/PRINCIPAL FINDINGS: The diuretic agent ethacrynic acid (EA was identified as a Wnt inhibitor using a cell-based Wnt reporter assay. In vitro assays further confirmed the inhibitory effect of EA on Wnt/beta-catenin signaling. Cell viability assays showed that EA selectively induced cell death in primary CLL cells. Exposure of CLL cells to EA decreased the expression of Wnt/beta-catenin target genes, including LEF-1, cyclin D1 and fibronectin. Immune co-precipitation experiments demonstrated that EA could directly bind to LEF-1 protein and destabilize the LEF-1/beta-catenin complex. N-acetyl-L-cysteine (NAC, which can react with the alpha, beta-unsaturated ketone in EA, but not other anti-oxidants, prevented the drug's inhibition of Wnt/beta-catenin activation and its ability to induce apoptosis in CLL cells. CONCLUSIONS/SIGNIFICANCE: Our studies indicate that EA selectively suppresses CLL survival due to inhibition of Wnt/beta-catenin signaling. Antagonizing Wnt signaling in CLL with EA or related drugs may represent an effective treatment of this disease.

  8. Does Selection and Management of Patients with Chronic Kidney Disease In Government Run and Private Hospitals Differ?

    Science.gov (United States)

    Gowda, Anoop; Dutt, Aswini Raghavendra; Bangera, Shobith

    2017-08-01

    Globally, incidence of Chronic Kidney Disease (CKD) is rapidly rising with huge burden on the life expectancy of the patients. Regular haemodialysis improves the quality of life in these patients. They get treatment at either government run or private sector hospitals. A difference in disease pattern, comorbidity, patient management and number of access failures can be observed in these set ups. The present study was carried out to find out selection, management and disease pattern of CKD patients admitted for dialysis in government run and private hospital. A cross-sectional study on patients (18-90 years) admitted and undergoing dialysis at government run (N=129) and private hospital (N=182) was undertaken in Karnataka, India. Parameters like comorbidity (diabetes), number of dialysis per week, number of access failures, and follow up visits were compared between these patients. Chi- squared test was used to compare the data. All tests were two-tailed and pgender bias in selection of patients for dialysis between the two hospitals. Similarly, follow-ups with nephrologist, number of dialysis done per week and erythropoietin supplements administered were significantly more among private hospital patients (pprivate hospital. No statistical difference was seen with access failure in both these setups. No bias in management of CKD patient was seen among the two sets of hospitals though available facilities seemed to vary.

  9. 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.

  10. Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

    Science.gov (United States)

    Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

    2006-01-01

    CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (Pphenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

  11. Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.

    Science.gov (United States)

    Shimano, Y; Kumazaki, M; Sakurai, T; Hida, H; Fujimoto, I; Fukuda, A; Nishino, H

    1995-12-01

    Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.

  12. 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...

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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...

  18. Selective toxicity of persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting.

    Science.gov (United States)

    Salimi, Ahmad; Motallebi, Abbasali; Ayatollahi, Maryam; Seydi, Enayatollah; Mohseni, Ali Reza; Nazemi, Melika; Pourahmad, Jalal

    2017-04-01

    Natural products isolated from marine environment are well known for their pharmacodynamic potential in diversity of disease treatments such as cancer or inflammatory conditions. Sea cucumbers are one of the marine animals of the phylum Echinoderm. Many studies have shown that the sea cucumber contains antioxidants and anti-cancer compounds. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5 + B lymphocytes. CLL is the most common leukemia in adults, about 25-30% of all leukemias. In this study B lymphocytes and their mitochondria (cancerous and non-cancerous) were obtained from peripheral blood of human subjects and B lymphocyte cytotoxicity assay, and caspase 3 activation along with mitochondrial upstream events of apoptosis signaling including reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and mitochondrial swelling were determined following the addition of Holothuria parva extract to both cancerous and non-cancerous B lymphocytes and their mitochondria. Our in vitro finding showed that mitochondrial ROS formation, MMP collapse, and mitochondrial swelling and cytochrome c release were significantly (P < 0.05) increased after addition of different concentrations of H. parva only in cancerous BUT NOT normal non-cancerous mitochondria. Consistently, different concentrations of H. parva significantly (P < 0.05) increased cytotoxicity and caspase 3 activation only in cancerous BUT NOT normal non-cancerous B lymphocytes. These results showed that H. parva methanolic extract has a selective mitochondria mediated apoptotic effect on chronic lymphocytic leukemia B lymphocytes hence may be promising in the future anticancer drug development for treatment of CLL. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1158-1169, 2017. © 2016 Wiley Periodicals, Inc.

  19. 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.

  20. Brain indices of nicotine's effects on attentional bias to smoking and emotional pictures and to task-relevant targets.

    Science.gov (United States)

    Gilbert, David G; Sugai, Chihiro; Zuo, Yantao; Rabinovich, Norka E; McClernon, F Joseph; Froeliger, Brett

    2007-03-01

    Aversive and smoking-related stimuli are related to smoking urges and relapse and can be potent distractors of selective attention. It has been suggested that the beneficial effect of nicotine replacement therapy may be mediated partly by the ability of nicotine to reduce distraction by such stimuli and thereby to facilitate attention to task-relevant stimuli. The present study tested the hypothesis that nicotine reduces distraction by aversive and smoking-related stimuli as indexed by the parietal P3b brain response to a task-relevant target digit. We assessed the effect of nicotine on distraction by emotionally negative, positive, neutral, and smoking-related pictures immediately preceding target digits during a rapid visual information processing task in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included two experimental sessions. After overnight smoking deprivation (12+ hr), active nicotine patches were applied to participants during one of the sessions and placebo patches were applied during the other session. Nicotine enhanced P3b responses associated with target digits immediately subsequent to negative emotional pictures bilaterally and subsequent to smoking-related pictures only in the right hemisphere. No effects of nicotine were observed for P3bs subsequent to positive and neutral distractor pictures. Another measure of attention, contingent negative variation amplitude in anticipation of the target digits also was increased by nicotine, especially in the left hemisphere and at posterior sites. Together, these findings suggest that nicotine reduces the distraction by emotionally negative and smoking-related stimuli and promotes attention to task-related stimuli by modulating somewhat lateralized and task-specific neural networks.

  1. Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice123

    Science.gov (United States)

    Storey, Granville P.; Heimbigner, Lauren; Walwyn, Wendy M.; Bamford, Nigel S.

    2016-01-01

    Abstract Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promotes corticostriatal activity and locomotor sensitization through upstream changes in the activity of tonically active cholinergic interneurons (ChIs). We used a model of operant drug-taking behaviors, in which mice self-administered amphetamine through an in-dwelling catheter. Mice acquired amphetamine self-administration under fixed and increasing schedules of reinforcement. Following a period of abstinence, we determined whether nicotinic acetylcholine receptors modified drug-seeking behavior and associated alterations in ChI firing and corticostriatal activity. Mice responding to conditioned reinforcement showed reduced ChI and corticostriatal activity ex vivo, which paradoxically increased following an amphetamine challenge. Nicotine, in a concentration that increases Ca2+ influx and desensitizes α4β2*-type nicotinic receptors, reduced amphetamine-seeking behaviors following abstinence and amphetamine-induced locomotor sensitization. Nicotine blocked the depression of ChI firing and corticostriatal activity and the potentiating response to an amphetamine challenge. Together, these results demonstrate that nicotine reduces reward-associated behaviors following repeated amphetamine and modifies the changes in ChIs firing and corticostriatal activity. By returning glutamatergic activity in amphetamine self-administering mice to a more stable and normalized state, nicotine limits the depression of striatal activity in withdrawal and the increase in activity following

  2. 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

  3. Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition

    DEFF Research Database (Denmark)

    Kachel, Hamid S; Patel, Rohit N; Franzyk, Henrik

    2016-01-01

    -fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes. Whole-cell currents...

  4. Conformationally restrained carbamoylcholine homologues. Synthesis, pharmacology at neuronal nicotinic acetylcholine receptors and biostructural considerations

    DEFF Research Database (Denmark)

    de la Fuente Revenga, M; Balle, Thomas; Jensen, Anders A.

    2015-01-01

    Exploration of small selective ligands for the nicotinic acetylcholine receptors (nAChRs) based on acetylcholine (ACh) has led to the development of potent agonists with clear preference for the α4β2 nAChR, the most prevalent nAChR subtype in the central nervous system. In this work we present...

  5. alpha(7) Nicotinic acetylcholine receptor activation prevents behavioral and molecular changes induced by repeated phencyclidine treatment

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Christensen, Ditte Z; Hansen, Henrik H

    2009-01-01

    in a modified Y-maze test. Polymorphisms in the alpha(7) nicotinic acetylcholine receptor (nAChR) gene have been linked to schizophrenia. Here we demonstrate that acute administration of the selective alpha(7) nAChR partial agonist SSR180711 dose-dependently reversed the behavioral impairment induced by PCP...

  6. Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hay-Schmidt, Anders; Hansen, Henrik H

    2010-01-01

    alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR agonists, such as SSR180711, activate neurons in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions...

  7. 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

  8. 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

  9. 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...

  10. 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

  11. 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

  12. 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.

  13. Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Olsen, G M; Wiborg, O

    2009-01-01

    Current literature suggests involvement of nicotinic acetylcholine receptors (nAChRs) in major depression. However, it is controversial whether the antidepressant-like effect of nAChR modulation is induced by activation, desensitization or inhibition of central nAChRs. In addition, the specific n......AChR subtype/s involved remains unknown. In this study, we systematically compared the effects of non-selective and selective nicotinic agonists and antagonists in two different tests for antidepressant effects in mice: the tail suspension test and the forced swim test. Compounds: nicotine, RJR-2403 (alpha4...

  14. A new IRAK-M-mediated mechanism implicated in the anti-inflammatory effect of nicotine via α7 nicotinic receptors in human macrophages.

    Directory of Open Access Journals (Sweden)

    Maria C Maldifassi

    Full Text Available Nicotine stimulation of α7 nicotinic acetylcholine receptor (α7 nAChR powerfully inhibits pro-inflammatory cytokine production in lipopolysaccharide (LPS-stimulated macrophages and in experimental models of endotoxemia. A signaling pathway downstream from the α7 nAChRs, which involves the collaboration of JAK2/STAT3 and NF-κB to interfere with signaling by Toll-like receptors (TLRs, has been implicated in this anti-inflammatory effect of nicotine. Here, we identifiy an alternative mechanism involving interleukin-1 receptor-associated kinase M (IRAK-M, a negative regulator of innate TLR-mediated immune responses. Our data show that nicotine up-regulates IRAK-M expression at the mRNA and protein level in human macrophages, and that this effect is secondary to α7 nAChR activation. By using selective inhibitors of different signaling molecules downstream from the receptor, we provide evidence that activation of STAT3, via either JAK2 and/or PI3K, through a single (JAK2/PI3K/STAT3 or two convergent cascades (JAK2/STAT3 and PI3K/STAT3, is necessary for nicotine-induced IRAK-M expression. Moreover, down-regulation of this expression by small interfering RNAs specific to the IRAK-M gene significantly reverses the anti-inflammatory effect of nicotine on LPS-induced TNF-α production. Interestingly, macrophages pre-exposed to nicotine exhibit higher IRAK-M levels and reduced TNF-α response to an additional LPS challenge, a behavior reminiscent of the 'endotoxin tolerant' phenotype identified in monocytes either pre-exposed to LPS or from immunocompromised septic patients. Since nicotine is a major component of tobacco smoke and increased IRAK-M expression has been considered one of the molecular determinants for the induction of the tolerant phenotype, our findings showing IRAK-M overexpression could partially explain the known influence of smoking on the onset and progression of inflammatory and infectious diseases.

  15. Evaluation of PET Radioligands for the neuronal nicotinic acetylcholine receptor

    International Nuclear Information System (INIS)

    Schoenbaechler, R.; Westera, G.; Nan-Horng Lin

    2002-01-01

    Full text: A-186253.1, a compound made by Abbott laboratories, was labelled with carbon-11 and evaluated as a PET ligand for the neuronal nicotinic acetylcholine receptor (nAChR). The compound was labelled with C-11 by methylation with 11C-MeI of the desmethyl precursor A-183828.1. The affinity of A-186253.1 for the α4β2 and the α7 subtype of the nAChR was determined in displacement studies. PET-studies were performed in rats and pigs Inhibitory constants (K i ) versus cytsine were 461 ± 99 pM for A-186253.1 and versus α-Bungarotoxin >100 μM. which means a very high selectivity for the α4β2-receptor (>227,000). Highest uptake of [ 11 C]-A-186253.1 was observed in the thalamus where an increase in radiotracer uptake was seen until 45 min p.i.. Thereafter, the radiotracer concentration remained constant until the end of the scan indicating slow washout of [ 11 C]-A-186253.1. Application of cold A-186253.1 (0.5 mg/kg) 40 min p.i. resulted in a decrease in radiotracer concentration in the thalamus and the cortex indicating displacement of [ 11 C]-A-186253.1. Blockade studies with cytisine (0.5 mg/kg), a selective ligand for the α4β2 nicotinic receptor, showed just a slight reduction of the radioligand uptake in the thalamus and in the cortex whereas the blockade with cold A-186253.1 (1 mg/kg) resulted in a 50 % reduction. These results suggest, that 50 % of the [ 11 C]-A-186253.1 in the brain corresponds to specifically bound radioligand, but not to the α4β2 subtype of the nicotinic receptor. (author)

  16. Selective decrease of components of the creatine kinase system and ATP synthase complex in chronic Chagas disease cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Priscila Camillo Teixeira

    2011-06-01

    Full Text Available BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC and ischemic (IC cardiomyopathies. METHODOLOGY/PRINCIPAL FINDINGS: Myocardium homogenates from CCC (N=5, IC (N=5 and IDC (N=5 patients, as well as from heart donors (N=5 were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit and muscular creatine kinase (CKM and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. CONCLUSIONS/SIGNIFICANCE: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.

  17. A preclinical study on the rescue of normal tissue by nicotinic acid in high-dose treatment with APO866, a specific nicotinamide phosphoribosyltransferase inhibitor

    DEFF Research Database (Denmark)

    Olesen, Uffe Høgh; Thougaard, Annemette V; Jensen, Peter Buhl

    2010-01-01

    Inhibitor of nicotinamide phosphoribosyltransferase APO866 is a promising cancer drug currently in phase II clinical trials in oncology. Here, we present a strategy for increasing the therapeutic potential of APO866 through the rescue of normal tissues by coadministration of nicotinic acid (Vitamin...... B(3)). We examined the toxicity profile of APO866 in B6D2F1 mice and the effect of oral administration of nicotinic acid on tissue toxicity. Nicotinic acid (50 mg/kg) protects mice from death and severe toxicity from an APO866 dose (60 mg/kg) four times the monotherapy maximum tolerated dose (15 mg....../kg). In a panel of six cancer cell lines, we find that three (including ML-2 cells) are protected by nicotinic acid in vitro, whereas the cytotoxicity of APO866 remains unaffected in the remaining three (including A2780 cells). A selective biomarker for the protection by nicotinic acid was subsequently identified...

  18. A Flexible Label-Free Biosensor Sensitive and Selective to TNF-a: Application for Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Abdoullatif BARAKET

    2014-05-01

    Full Text Available Tumor necrosis factor-a (TNF-a is a key pro-inflammatory cytokine that is characterized by elevated circulating levels for chronic heart failure (CHF and left ventricular assisted device (LVAD implantation patients, respectively. Therefore, a rapid and ease-of-use diagnostic tool is required to monitor LVAD patients at a high risk of mortality during early expression of an inflammatory storm. In this paper, we report on the quantitative electrochemical detection of human TNF-a with its corresponding antibody (Ab immobilized onto the functionalized biosensor surface. The label-free biosensor was fabricated on a gold surface that was deposited on a flexible polyimide (PI substrate. The interfacial properties of the functionalized flexible gold electrodes were evaluated by cyclic voltammetry (CV in the presence of Fe(CN64-/3- as the redox-active species. Afterwards, the electrochemical impedance spectroscopy (EIS technique was used to determine the TNF-a concentrations. EIS results confirmed that the developed flexible biosensor can accurately detect TNF-a with a good sensitivity in the dynamic range of 0.1 pg/mL to 0.5 ng/mL. Overall, the developed flexible biosensor was easy to fabricate and the results demonstrate a good selectivity in the presence of other cytokines such as interleukin: (IL-10 and (IL-1.

  19. Selection of mutants resistant to black spot disease by chronic irradiation of gamma-rays in Japanese pear 'Osanijisseiki'

    International Nuclear Information System (INIS)

    Masuda, Tetsuo; Yoshioka, Toji; Kotobuki, Kazuo; Sanada, Tetsuro; Inoue, Kosuke; Murata, Kenji; Kitagawa, Kenichi; Tabira, Hiroki; Yoshida, Akira

    1997-01-01

    'Osanijisseiki', a self-compatible, spontaneous bud sport of the Japanese pear 'Nijisseiki' is an excellent cultivar with a smooth skin. However, this cultivar is susceptible to Japanese pear black spot disease caused by Alternaria alternata Japanese pear pathotype. To obtain resistant mutants from 'Osanijisseiki', nursery plants of 'Osanijisseiki' have been irradiated chronically with gamma-rays in the Gamma Field of the Institute of Radiation Breeding, NAR, MAFF, since 1986. Screening tests using AK toxin, a host-specific toxin produced by A. alternata Japanese pear pathotype, were performed form 1988 to 1993. Four branches of young trees planted at a distance of 40 m from the 60 Co source were selected as being resistant mutants in 1991 (IRB 502-13T and IRB 502-14T) and 1993 (IRB 502-17T and IRB 502-18T). Sensitivity of the four resistant mutants to AK-toxin and susceptibility to the pathogen were compared with other of susceptible and resistant cultivars. The results showed that these four mutants possessed intermediate resistance. Furthermore, a mutant, IRB 502-13T, had the same characteristics as the original 'Osanijisseiki', except for the difference in toxin sensitivity. The characteristics of the other mutants, IRB 502 14-T, IRB 502-17T, and IRB 502-18T, care being examined. (author)

  20. 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

  1. Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats

    Directory of Open Access Journals (Sweden)

    Wei Zhong

    2015-10-01

    Full Text Available Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation.

  2. Direct and indirect associations between social anxiety and nicotine dependence and cessation problems: multiple mediator analyses.

    Science.gov (United States)

    Buckner, Julia D; Farris, Samantha G; Schmidt, Norman B; Zvolensky, Michael J

    2014-06-01

    Little empirical work has evaluated why socially anxious smokers are especially vulnerable to more severe nicotine dependence and cessation failure. Presumably, these smokers rely on cigarettes to help them manage their chronically elevated negative affect elicited by a wide array of social contexts. The current study examined the direct and indirect effects of social anxiety cross-sectionally in regard to a range of smoking processes among 466 treatment-seeking smokers. Negative affect and negative affect reduction motives were examined as mediators of the relations of social anxiety with nicotine dependence and cessation problems. Social anxiety was directly and robustly associated with perceived barriers to smoking cessation and problems experienced during past quit attempts. Social anxiety was also associated with greater nicotine dependence and smoking inflexibility indirectly through negative affect and negative affect smoking motives. Negative affect and smoking to reduce negative affect mediated these relations. These findings document the important role of negative affect and negative affect reduction motives in the relationships of social anxiety with nicotine dependence and cessation problems.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic mice.

    Science.gov (United States)

    Molas, Susanna; Gener, Thomas; Güell, Jofre; Martín, Mairena; Ballesteros-Yáñez, Inmaculada; Sanchez-Vives, Maria V; Dierssen, Mara

    2014-11-11

    Addiction involves long-lasting maladaptive changes including development of disruptive drug-stimuli associations. Nicotine-induced neuroplasticity underlies the development of tobacco addiction but also, in regions such as the hippocampus, the ability of this drug to enhance cognitive capabilities. Here, we propose that the genetic locus of susceptibility to nicotine addiction, the CHRNA5/A3/B4 gene cluster, encoding the α5, α3 and β4 subunits of the nicotinic acetylcholine receptors (nAChRs), may influence nicotine-induced neuroadaptations. We have used transgenic mice overexpressing the human cluster (TgCHRNA5/A3/B4) to investigate hippocampal structure and function in genetically susceptible individuals. TgCHRNA5/A3/B4 mice presented a marked reduction in the dendrite complexity of CA1 hippocampal pyramidal neurons along with an increased dendritic spine density. In addition, TgCHRNA5/A3/B4 exhibited increased VGLUT1/VGAT ratio in the CA1 region, suggesting an excitatory/inhibitory imbalance. These hippocampal alterations were accompanied by a significant impairment in short-term novelty recognition memory. Interestingly, chronic infusion of nicotine (3.25 mg/kg/d for 7 d) was able to rescue the reduced dendritic complexity, the excitatory/inhibitory imbalance and the cognitive impairment in TgCHRNA5/A3/B4. Our results suggest that chronic nicotine treatment may represent a compensatory strategy in individuals with altered expression of the CHRNA5/A3/B4 region.

  8. 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.

  9. 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

  10. 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...

  11. 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.

  12. 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: ...

  13. 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

  14. 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

  15. Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

    International Nuclear Information System (INIS)

    El-Mas, Mahmoud M.; Fouda, Mohamed A.; El-gowilly, Sahar M.; Saad, Evan I.

    2012-01-01

    We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE 2 ) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS PE and BRS SNP ). Nicotine (100 μg/kg i.v.) reduced BRS SNP in OVX rats but not in proestrus or OVXE 2 rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS PE was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS SNP interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS SNP attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E 2 against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.

  16. Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

    Science.gov (United States)

    Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

    2015-12-01

    Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For

  17. 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.

  18. A systematic review of consumer preference for e-cigarette attributes: Flavor, nicotine strength, and type

    Science.gov (United States)

    Nemati, Mehdi; Zheng, Yuqing

    2018-01-01

    Objective Systematic review of research examining consumer preference for the main electronic cigarette (e-cigarette) attributes namely flavor, nicotine strength, and type. Method A systematic search of peer-reviewed articles resulted in a pool of 12,933 articles. We included only articles that meet all the selection criteria: (1) peer-reviewed, (2) written in English, and (3) addressed consumer preference for one or more of the e-cigarette attributes including flavor, strength, and type. Results 66 articles met the inclusion criteria for this review. Consumers preferred flavored e-cigarettes, and such preference varied with age groups and smoking status. We also found that several flavors were associated with decreased harm perception while tobacco flavor was associated with increased harm perception. In addition, some flavor chemicals and sweeteners used in e-cigarettes could be of toxicological concern. Finally, consumer preference for nicotine strength and types depended on smoking status, e-cigarette use history, and gender. Conclusion Adolescents could consider flavor the most important factor trying e-cigarettes and were more likely to initiate vaping through flavored e-cigarettes. Young adults overall preferred sweet, menthol, and cherry flavors, while non-smokers in particular preferred coffee and menthol flavors. Adults in general also preferred sweet flavors (though smokers like tobacco flavor the most) and disliked flavors that elicit bitterness or harshness. In terms of whether flavored e-cigarettes assisted quitting smoking, we found inconclusive evidence. E-cigarette users likely initiated use with a cigarette like product and transitioned to an advanced system with more features. Non-smokers and inexperienced e-cigarettes users tended to prefer no nicotine or low nicotine e-cigarettes while smokers and experienced e-cigarettes users preferred medium and high nicotine e-cigarettes. Weak evidence exists regarding a positive interaction between menthol

  19. A systematic review of consumer preference for e-cigarette attributes: Flavor, nicotine strength, and type.

    Science.gov (United States)

    Zare, Samane; Nemati, Mehdi; Zheng, Yuqing

    2018-01-01

    Systematic review of research examining consumer preference for the main electronic cigarette (e-cigarette) attributes namely flavor, nicotine strength, and type. A systematic search of peer-reviewed articles resulted in a pool of 12,933 articles. We included only articles that meet all the selection criteria: (1) peer-reviewed, (2) written in English, and (3) addressed consumer preference for one or more of the e-cigarette attributes including flavor, strength, and type. 66 articles met the inclusion criteria for this review. Consumers preferred flavored e-cigarettes, and such preference varied with age groups and smoking status. We also found that several flavors were associated with decreased harm perception while tobacco flavor was associated with increased harm perception. In addition, some flavor chemicals and sweeteners used in e-cigarettes could be of toxicological concern. Finally, consumer preference for nicotine strength and types depended on smoking status, e-cigarette use history, and gender. Adolescents could consider flavor the most important factor trying e-cigarettes and were more likely to initiate vaping through flavored e-cigarettes. Young adults overall preferred sweet, menthol, and cherry flavors, while non-smokers in particular preferred coffee and menthol flavors. Adults in general also preferred sweet flavors (though smokers like tobacco flavor the most) and disliked flavors that elicit bitterness or harshness. In terms of whether flavored e-cigarettes assisted quitting smoking, we found inconclusive evidence. E-cigarette users likely initiated use with a cigarette like product and transitioned to an advanced system with more features. Non-smokers and inexperienced e-cigarettes users tended to prefer no nicotine or low nicotine e-cigarettes while smokers and experienced e-cigarettes users preferred medium and high nicotine e-cigarettes. Weak evidence exists regarding a positive interaction between menthol flavor and nicotine strength.

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

    Science.gov (United States)

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

    2011-12-10

    sport practice (50 ng/mL for nicotine, cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N'-oxide, cotinine-N-oxide, anabasine, anatabine and nornicotine) revealed a prevalence of 15.3% amongst athletes. While this number may appear lower than the worldwide smoking prevalence of around 25%, focusing the study on selected sports highlighted more alarming findings. Indeed, active nicotine consumption in ice hockey, skiing, biathlon, bobsleigh, skating, football, basketball, volleyball, rugby, American football, wrestling and gymnastics was found to range between 19.0 and 55.6%. Therefore, considering the adverse effects of smoking on the respiratory tract and numerous health threats detrimental to sport practice at top level, likelihood of smokeless tobacco consumption for performance enhancement is greatly supported. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. 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...

  2. 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

  3. 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

  4. Chronic Periprosthetic Hip Joint Infection. A Retrospective, Observational Study on the Treatment Strategy and Prognosis in 130 Non-Selected Patients

    DEFF Research Database (Denmark)

    Lange, Jeppe; Troelsen, Anders; Søballe, Kjeld

    2016-01-01

    INTRODUCTION: Limited information is available regarding the treatment strategy and prognosis of non-selected patients treated for chronic periprosthetic hip joint infection. Such information is important as no head-to-head studies on treatment strategies are available. The purpose of this study...... is to report on the treatment strategy and prognosis of a non-selected, consecutive patient population. METHODS: We identified 130 patients in the National Patient Registry, consecutively treated for a chronic periprosthetic hip joint infection between 2003-2008 at 11 departments of orthopaedic surgery. We...... extracted information regarding patient demographics, treatment and outcome. 82 patients were re-implanted in a two-stage revision (national standard), the remaining 48 were not re-implanted in a two-stage revision. We were able to collect up-to-date information on all patients to date of death or medical...

  5. 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.

  6. SIB-1553A, (+/-)-4-[[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride, a subtype-selective ligand for nicotinic acetylcholine receptors with putative cognitive-enhancing properties: effects on working and reference memory performances in aged rodents and nonhuman primates.

    Science.gov (United States)

    Bontempi, B; Whelan, K T; Risbrough, V B; Rao, T S; Buccafusco, J J; Lloyd, G K; Menzaghi, F

    2001-10-01

    Preclinical and clinical data have suggested the potential use of nicotinic acetylcholine receptor (nAChR) ligands for treating cognitive dysfunction associated with neurodegenerative diseases, such as Alzheimer's disease. SIB-1553A, (+/-)-4-[[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride, a novel nAChR ligand with predominant agonist subtype selectivity for beta4 subunit-containing human neuronal nAChRs, was tested in a variety of cognitive paradigms in aged rodents and nonhuman primates after acute and repeated administration. Subcutaneous administration of SIB-1553A improved delayed nonmatching to place performance in aged mice. In aged rhesus monkeys, intramuscular and oral administration of SIB-1553A improved choice accuracy in a delayed matching to sample task. SIB-1553A improved performances in these spatial and nonspatial working memory tasks but was less effective at improving performances in spatial reference memory tasks (i.e., aged rodents exposed to a discrimination task in a T-maze or trained to locate a hidden platform in a water maze). These data suggest that SIB-1553A has a predominant effect on attention/working memory processes. SIB-1553A also induced the release of acetylcholine in the hippocampus of aged rats and was equally effective whether administered acutely or repeatedly (6 weeks of daily subcutaneous administration). Thus, rats repeatedly treated with SIB-1553A exhibit neither tolerance nor sensitization to the effects of the compound. The SIB-1553A-induced cognitive improvement may be in part related to an increase in cholinergic function. The present study provides additional support for the use of subtype-selective nAChR ligands as a potential therapy for the symptomatic treatment of specific cognitive deficits (such as attention/working memory deficits) associated with aging and neurological diseases.

  7. Thermochemistry of aqueous pyridine-3-carboxylic acid (nicotinic acid)

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, Elsa M. [Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade de Lisboa, 1749-016 Lisboa (Portugal); Instituto Politecnico de Setubal, ESTBarreiro, Rua Americo da Silva Marinho, 2839-001 Lavradio (Portugal); Rego, Talita S. [Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade de Lisboa, 1749-016 Lisboa (Portugal); Minas da Piedade, Manuel E., E-mail: memp@fc.ul.p [Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade de Lisboa, 1749-016 Lisboa (Portugal)

    2011-06-15

    Research highlights: {yields} We determined the {Delta}{sub sol}H{sub m} of solid nicotinic acid (NA) in water by solution calorimetry. {yields} We determined {Delta}{sub dil}H{sub m} of an aqueous nicotinic acid solution by flow calorimetry. {yields} We determined (aq, {infinity}) for the 3 NA species involved in acid/base equilibria. {yields} We determined the enthalpy of formation of NA(aq) under saturation conditions.. - Abstract: The molar enthalpy of solution of solid nicotinic acid (NA) at T = 298.15 K, to give an aqueous solution of molality m = 3.748 . 10{sup -3} mol {center_dot} kg{sup -1}, was determined as {Delta}{sub sol}H{sub m} = (19,927 {+-} 48) J {center_dot} mol{sup -1}, by solution calorimetry. Enthalpies of dilution, {Delta}{sub dil}H{sub m}, of 0.1005 mol {center_dot} kg{sup -1} aqueous nicotinic acid to yield final solutions with molality in the approximate range (0.03 to 0.09) mol {center_dot} kg{sup -1} were also measured by flow calorimetry. Combining the two sets of data and the results of pH measurements, with values of proton dissociation enthalpies and {Delta}{sub f}H{sub m}{sup 0}(NA, cr) selected from the literature, it was possible to derive the standard molar enthalpies of formation of the three nicotinic acid species involved in protonation/deprotonation equilibria, at infinite dilution: {Delta}{sub f}H{sub m}{sup 0}(HN{sup +}C{sub 5}H{sub 4}COOH.{infinity}H{sub 2}O,aq) = (328.2 {+-} 1.2) kJ {center_dot} mol{sup -1}, {Delta}{sub f}H{sub m}{sup 0}(HN{sup +}C{sub 5}H{sub 4}COO{sup -}.{infinity}H{sub 2}O,aq) = (325.0 {+-} 1.2) kJ {center_dot} mol{sup -1}, and {Delta}{sub f}H{sub m}{sup 0}(NC{sub 5}H{sub 4}COO{sup -}.{infinity}H{sub 2}O,aq) = (313.7 {+-} 1.2) kJ {center_dot} mol{sup -1}. Finally, the enthalpy of solution of nicotinic acid at T = 298.15 K, under saturation conditions (m = 0.138 mol {center_dot} kg{sup -1}), and the standard molar enthalpy of formation of the corresponding solution could also be obtained as {Delta

  8. Use of selected complementary and alternative medicine (CAM) treatments in veterans with cancer or chronic pain: a cross-sectional survey

    OpenAIRE

    McEachrane-Gross, F Patricia; Liebschutz, Jane M; Berlowitz, Dan

    2006-01-01

    Abstract Background Complementary and alternative medicine (CAM) is emerging as an important form of care in the United States. We sought to measure the prevalence of selected CAM use among veterans attending oncology and chronic pain clinics and to describe the characteristics of CAM use in this population. Methods The self-administered, mail-in survey included questions on demographics, health beliefs, medical problems and 6 common CAM treatments (herbs, dietary supplements, chiropractic ca...

  9. 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.

  10. A synthetic combinatorial strategy for developing a-conotoxin analogs as potent a7 nicotinic acetylcholine receptor antagonists

    DEFF Research Database (Denmark)

    Armishaw, Christopher J; Singh, Narender; Medina-Franco, Jose L

    2010-01-01

    alpha-Conotoxins are peptide neurotoxins isolated from venomous cone snails that display exquisite selectivity for different subtypes of nicotinic acetylcholine receptors (nAChR). They are valuable research tools that have profound implications in the discovery of new drugs for a myriad of neurop......alpha-Conotoxins are peptide neurotoxins isolated from venomous cone snails that display exquisite selectivity for different subtypes of nicotinic acetylcholine receptors (nAChR). They are valuable research tools that have profound implications in the discovery of new drugs for a myriad...

  11. 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

  12. 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.)

  13. Glycerol particle cigarettes: a less harmful option for chronic smokers.

    Science.gov (United States)

    Sutherland, G; Russell, M A; Stapleton, J A; Feyerabend, C

    1993-01-01

    In 20 smokers who switched to a new type of virtually tar free cigarette for three days, average nicotine intake was reduced by 44%, carbon monoxide intake increased by 19%, while estimated tar intake was reduced by about 90%. Such cigarettes pose substantially less risk of cancer and chronic obstructive lung disease than conventional cigarettes, and their acceptability and safety could be improved by increasing nicotine yield, reducing carbon monoxide yield, and improving the flavour. PMID:8511737

  14. Moving out of the laboratory: does nicotine improve everyday attention?

    Science.gov (United States)

    Rusted, J M; Caulfield, D; King, L; Goode, A

    2000-11-01

    The most robust demonstrations of the nicotine-related performance effects on human cognitive processes are seen in tasks that measure attention. If nicotine does have some potential for enhancing attention, the obvious question to ask is whether the effects demonstrated in the laboratory hold any significance for real-life performance. This paper describes three studies that compare the effects in smokers of a single own brand cigarette on laboratory tests of attention and on everyday analogues of these laboratory tasks. In the laboratory measures of sustained attention and in the everyday analogue, performance advantages were registered in the smoking condition. These benefits were observed in smokers who abstained for a self-determined period of not less than 2 h. The studies were unable to replicate previous research reporting positive effects of smoking on a laboratory task of selective attention, the Stroop task. Small but significant improvements in performance were registered in the everyday analogues, which involved sustaining attention in a dual task situation, a telephone directory search task and a map search task. In addition, smokers showed a significant colour-naming decrement for smoking-related stimuli in the Stroop task. This attentional bias towards smoking-related words occurred independent of whether they had abstained or recently smoked an own brand cigarette. The effect is discussed in terms of the two-component model of processing bias for emotionally valenced stimuli.

  15. 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.

  16. 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...

  17. 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...

  18. Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients.

    Science.gov (United States)

    Llewellyn, Martin S; Messenger, Louisa A; Luquetti, Alejandro O; Garcia, Lineth; Torrico, Faustino; Tavares, Suelene B N; Cheaib, Bachar; Derome, Nicolas; Delepine, Marc; Baulard, Céline; Deleuze, Jean-Francois; Sauer, Sascha; Miles, Michael A

    2015-04-01

    Chagas disease results from infection with the diploid protozoan parasite Trypanosoma cruzi. T. cruzi is highly genetically diverse, and multiclonal infections in individual hosts are common, but little studied. In this study, we explore T. cruzi infection multiclonality in the context of age, sex and clinical profile among a cohort of chronic patients, as well as paired congenital cases from Cochabamba, Bolivia and Goias, Brazil using amplicon deep sequencing technology. A 450bp fragment of the trypomastigote TcGP63I surface protease gene was amplified and sequenced across 70 chronic and 22 congenital cases on the Illumina MiSeq platform. In addition, a second, mitochondrial target--ND5--was sequenced across the same cohort of cases. Several million reads were generated, and sequencing read depths were normalized within patient cohorts (Goias chronic, n = 43, Goias congenital n = 2, Bolivia chronic, n = 27; Bolivia congenital, n = 20), Among chronic cases, analyses of variance indicated no clear correlation between intra-host sequence diversity and age, sex or symptoms, while principal coordinate analyses showed no clustering by symptoms between patients. Between congenital pairs, we found evidence for the transmission of multiple sequence types from mother to infant, as well as widespread instances of novel genotypes in infants. Finally, non-synonymous to synonymous (dn:ds) nucleotide substitution ratios among sequences of TcGP63Ia and TcGP63Ib subfamilies within each cohort provided powerful evidence of strong diversifying selection at this locus. Our results shed light on the diversity of parasite DTUs within each patient, as well as the extent to which parasite strains pass between mother and foetus in congenital cases. Although we were unable to find any evidence that parasite diversity accumulates with age in our study cohorts, putative diversifying selection within members of the TcGP63I gene family suggests a link between genetic diversity within this gene

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Rationale for selecting antihistamine drugs for the therapy of chronic urticaria in terms of efficacy and safety

    Directory of Open Access Journals (Sweden)

    O. V. Skorokhodkina

    2014-01-01

    Full Text Available Goal of the study. To compare the efficacy of antihistamine drugs for the therapy of chronic urticaria taking into consideration their effect on the patients’ cognitive functions. Materials and methods. The study involved 178 patients with chronic urticaria who were divided into six groups taking second generation antihistamine drugs: Cetirizine (n = 38, Levocetirizine (n = 27, Fexofenadine (n=26, Ebastine (n = 33, Loratadine (n = 26 and Desloratadine (n = 28. The patients recorded dynamic changes in clinical symptoms of the disease (number of urticarial components, skin itching intensity, availability or absence of urticarial derniographism, angioedema signs and signs of the shortness of breath and reduced blood pressure in their individual diaries. Baseline signs of the patients’ cognitive condition and those recorded during the treatment were studied using the Kraepelin’s arithmetic test (modified by Schulte, I.M. Lushchikhina’s verbal and visual thinking assessment method and method for memorizing ten words. The control group comprised 31 subjects without chronic urticaria. Results of the study. Ebastine and Fexofenadine are the most efficient antihistamine drugs for the treatment of chronic urticaria. At the same time, they do not have any negative effect on the patients’ cognitive functions so they can be recommended for long-term treatment of chronic urticaria. In spite of its evident positive therapeutic effect, Cetirizine reduces mental alertness and deteriorates thinking in patients with chronic urticaria. Because of this, the drug must be prescribed with care for long-term administration to those patients whose professional activities demand increased attention concentration. Loratadine has a positive effect on the patients’ attention and thinking. However, taking into consideration its low efficacy, the drug can be prescribed as the basis therapy for the treatment of light forms of chronic urticaria.

  5. 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.

  6. The 15q24/25 Susceptibility Variant for Lung Cancer and Chronic Obstructive Pulmonary Disease Is Associated with Emphysema

    NARCIS (Netherlands)

    Lambrechts, Diether; Buysschaert, Ian; Zanen, Pieter; Coolen, Johan; Lays, Natacha; Cuppens, Harry; Groen, Harry J. M.; Dewever, Walter; van Klaveren, Rob J.; Verschakelen, Johny; Wijmenga, Cisca; Postma, Dirkje S.; Decramer, Marc; Janssens, Wim

    2010-01-01

    Rationale: Genome-wide association studies have identified genetic variants in the nicotinic acetylcholine receptor (nAChR) on chromosome 15q24/25 as a risk for nicotine dependence, lung cancer, and chronic obstructive pulmonary disease (COPD). Assessment of bronchial obstruction by spirometry,

  7. Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation

    Directory of Open Access Journals (Sweden)

    Tasnim S. Mohamed

    2015-11-01

    Full Text Available Nicotine addiction, the result of tobacco use, leads to over six million premature deaths world-wide, a number that is expected to increase by a third within the next two decades. While more than half of smokers want and attempt to quit, only a small percentage of smokers are able to quit without pharmacological interventions. Therefore, over the past decades, researchers in academia and the pharmaceutical industry have focused their attention on the development of more effective smoking cessation therapies, which is now a growing 1.9 billion dollar market. Because the role of neuronal nicotinic acetylcholine receptors (nAChR in nicotine addiction is well established, nAChR based therapeutics remain the leading strategy for smoking cessation. However, the development of neuronal nAChR drugs that are selective for a nAChR subpopulation is challenging, and only few neuronal nAChR drugs are clinically available. Among the many neuronal nAChR subtypes that have been identified in the brain, the α4β2 subtype is the most abundant and plays a critical role in nicotine addiction. Here, we review the role of neuronal nAChRs, especially the α4β2 subtype, in the development and treatment of nicotine addiction. We also compare available smoking cessation medications and other nAChR orthosteric and allosteric ligands that have been developed with emphasis on the difficulties faced in the development of clinically useful compounds with high nAChR subtype selectivity.

  8. 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

  9. '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

  10. Effects of BMS-902483, an α7 nicotinic acetylcholine receptor partial agonist, on cognition and sensory gating in relation to receptor occupancy in rodents.

    Science.gov (United States)

    Pieschl, Rick L; Miller, Regina; Jones, Kelli M; Post-Munson, Debra J; Chen, Ping; Newberry, Kimberly; Benitex, Yulia; Molski, Thaddeus; Morgan, Daniel; McDonald, Ivar M; Macor, John E; Olson, Richard E; Asaka, Yukiko; Digavalli, Siva; Easton, Amy; Herrington, James; Westphal, Ryan S; Lodge, Nicholas J; Zaczek, Robert; Bristow, Linda J; Li, Yu-Wen

    2017-07-15

    The α7 nicotinic acetylcholine receptor is thought to play an important role in human cognition. Here we describe the in vivo effects of BMS-902483, a selective potent α7 nicotinic acetylcholine receptor partial agonist, in relationship to α7 nicotinic acetylcholine receptor occupancy. BMS-902483 has low nanomolar affinity for rat and human α7 nicotinic acetylcholine receptors and elicits currents in cells expressing human or rat α7 nicotinic acetylcholine receptors that are about 60% of the maximal acetylcholine response. BMS-902483 improved 24h novel object recognition memory in mice with a minimal effective dose (MED) of 0.1mg/kg and reversed MK-801-induced deficits in a rat attentional set-shifting model of executive function with an MED of 3mg/kg. Enhancement of novel object recognition was blocked by the silent α7 nicotinic acetylcholine receptor agonist, NS6740, demonstrating that activity of BMS-902483 was mediated by α7 nicotinic acetylcholine receptors. BMS-902483 also reversed ketamine-induced deficits in auditory gating in rats, and enhanced ex vivo hippocampal long-term potentiation examined 24h after dosing in mice. Results from an ex vivo brain homogenate binding assay showed that α7 receptor occupancy ranged from 64% (novel object recognition) to ~90% (set shift and gating) at the MED for behavioral and sensory processing effects of BMS-902483. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Appointment keeping for medical review among patients with selected chronic diseases in an urban area of Uganda.

    Science.gov (United States)

    Kalyango, Joan Nakayaga; Hall, Maurice; Karamagi, Charles

    2014-01-01

    Proper management of chronic diseases is important for prevention of disease complications and yet some patients miss appointments for medical review thereby missing the opportunity for proper monitoring of their disease conditions. There is limited information on missed appointments among chronic disease patients in resource limited settings. This study aimed to determine the prevalence of missed appointments for medical review and associated factors among chronic disease patients in an urban area of Uganda. Patients or caregivers of children with chronic diseases were identified as they bought medicines from a community pharmacy. They were visited at home to access their medical documents and those whose chronic disease status was ascertained were enrolled. The data was collected using: questionnaires, review of medical documents, and in-depth interviews with chronic disease patients. The prevalence of missed appointments was 42% (95%CI = 35-49%). The factors associated with missed appointments were: monthly income ≤30US Dollars (OR = 2.56, CI = 1.25-5.26), affording less than half of prescribed drugs (OR = 3.92, CI = 1.64-9.40), not experiencing adverse events (OR = 2.66, CI = 1.26-5.61), not sure if treatment helps (OR = 2.84, CI = 1.047.77), not having a medicines administration schedule (OR = 6.77, CI = 2.11-21.68), and increasing number of drugs (OR = 0.72, CI = 0.53-0.98). Patients missed appointments mainly due to: financial and health system barriers, conflicting commitments with appointments, and perceptions of the disease condition. Patients should be supported with accessible and affordable health services.

  12. Differential control of central cardiorespiratory interactions by hypercapnia and the effect of prenatal nicotine.

    Science.gov (United States)

    Huang, Zheng-Gui; Griffioen, Kathleen J S; Wang, Xin; Dergacheva, Olga; Kamendi, Harriet; Gorini, Christopher; Bouairi, Euguenia; Mendelowitz, David

    2006-01-04

    Hypercapnia evokes a strong cardiorespiratory response including gasping and a pronounced bradycardia; however, the mechanism responsible for these survival responses initiated in the brainstem is unknown. To examine the effects of hypercapnia on the central cardiorespiratory network, we used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and inhibitory synaptic neurotransmission to cardioinhibitory vagal neurons (CVNs). Hypercapnia differentially modulated inhibitory neurotransmission to CVNs; whereas hypercapnia selectively depressed spontaneous glycinergic IPSCs in CVNs without altering respiratory-related increases in glycinergic neurotransmission, it decreased both spontaneous and inspiratory-associated GABAergic IPSCs. Because maternal smoking is the highest risk factor for sudden infant death syndrome (SIDS) and prenatal nicotine exposure is proposed to be the link between maternal smoking and SIDS, we examined the cardiorespiratory responses to hypercapnia in animals exposed to nicotine in the prenatal and perinatal period. In animals exposed to prenatal nicotine, hypercapnia evoked an exaggerated depression of GABAergic IPSCs in CVNs with no significant change in glycinergic neurotransmission. Hypercapnia altered inhibitory neurotransmission to CVNs at both presynaptic and postsynaptic sites. Although the results obtained in this study in vitro cannot be extrapolated with certainty to in vivo responses, the results of this study provide a likely neurochemical mechanism for hypercapnia-evoked bradycardia and the dysregulation of this response with exposure to prenatal nicotine, creating a higher risk for SIDS.

  13. Expression of selected pathway-marker genes in human urothelial cells exposed chronically to a non-cytotoxic concentration of monomethylarsonous acid

    Directory of Open Access Journals (Sweden)

    Matthew Medeiros

    2014-01-01

    Full Text Available Bladder cancer has been associated with chronic arsenic exposure. Monomethylarsonous acid [MMA(III] is a metabolite of inorganic arsenic and has been shown to transform an immortalized urothelial cell line (UROtsa at concentrations 20-fold less than arsenite. MMA(III was used as a model arsenical to examine the mechanisms of arsenical-induced transformation of urothelium. A previous microarray analysis revealed only minor changes in gene expression at 1 and 2 months of chronic exposure to MMA(III, contrasting with substantial changes observed at 3 months of exposure. To address the lack of information between 2 and 3 months of exposure (the critical period of transformation, the expression of select pathway marker genes was measured by PCR array analysis on a weekly basis. Cell proliferation rate, anchorage-independent growth, and tumorigenicity in SCID mice were also assessed to determine the early, persistent phenotypic changes and their association with the changes in expression of these selected marker genes. A very similar pattern of alterations in these genes was observed when compared to the microarray results, and suggested that early perturbations in cell signaling cascades, immunological pathways, cytokine expression, and MAPK pathway are particularly important in driving malignant transformation. These results showed a strong association between the acquired phenotypic changes that occurred as early as 1–2 months of chronic MMA(III exposure, and the observed gene expression pattern that is indicative of the earliest stages in carcinogenesis.

  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. 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.

  17. 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.

  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. Chronic Pain and Selective Attention to Pain Arousing Daily Activity Pictures: Evidence From an Eye Tracking Study

    Directory of Open Access Journals (Sweden)

    Masoumeh Mahmoodi-Aghdam

    2017-11-01

    Conclusion: Although these results did not provide unequivocal support for the vigilance-avoidance hypothesis, they are generally consistent with the results of studies using eye tracking technology. Furthermore, our findings put a question over characterization of attentional biases in patients with chronic pain by simply relating that to difficulty in disengaging from pain-related stimuli.

  1. Comparison of the usefulness of selected formulas for GFR estimation in patients with diagnosed chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Paweł Wróbel

    2018-03-01

    Conclusions: CKD-EPI and abbreviated MDRD formulas have a similar usefulness in GFR value estimation in patients with diagnosed chronic kidney disease. Lower eGFR values achieved using abbreviated MDRD formula and CKD-EPI equation in comparison with Bjornsson’s formula may result in an increased number of patients diagnosed with CKD.

  2. Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A-317491, transiently attenuates cancer-induced bone pain in mice

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Nasser, Arafat; Falk, Sarah

    2012-01-01

    The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system almost exclusively confined to afferent sensory neurons, where they are found both at peripheral and central synapses. The P2X3 receptor is implicated in both neuropathic and inflammatory pain. However, the role of the ......X3 receptor in chronic cancer-induced bone pain is less known. Here we investigated the effect of systemic acute and chronic administration of the selective P2X3, P2X2/3 receptor antagonist (5-[[[(3-Phenoxyphenyl)methyl][(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl]-1...

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

    Science.gov (United States)

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

    2018-06-01

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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Nicotinic α4β2 receptor imaging agents

    International Nuclear Information System (INIS)

    Pichika, Rama; Easwaramoorthy, Balasubramaniam; Collins, Daphne; Christian, Bradley T.; Shi, Bingzhi; Narayanan, Tanjore K.; Potkin, Steven G.; Mukherjee, Jogeshwar

    2006-01-01

    The α4β2 nicotinic acetylcholine receptor (nAChR) has been implicated in various neurodegenerative diseases. Optimal positron emission tomography (PET) imaging agents are therefore highly desired for this receptor. We report here the development and initial evaluation of 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat brain homogenate using 3 H-cytisine exhibited a K i =0.50 nM for the α4β2 sites. The radiosynthesis of 2- 18 F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ( 18 F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40-50%, decay corrected. The specific activity was estimated to be approx. 37-185 GBq/μmol. In vitro autoradiography in rat brain slices indicated selective binding of 18 F-nifene to anteroventral thalamic (AVT) nucleus, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. Rat cerebellum showed some binding, whereas regions in the hippocampus had the lowest binding. The highest ratio of >13 between AVT and cerebellum was measured for 18 F-nifene in rat brain slices. The specific binding was reduced (>95%) by 300 μM nicotine in these brain regions. Positron emission tomography imaging study of 18 F-nifene (130 MBq) in anesthetized rhesus monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed selective maximal uptake in the regions of the anterior medial thalamus, ventro-lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including the subiculum. The cerebellum in the monkeys showed lower binding than the other regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a value of 2.2 and subsequently reduced. The faster binding profile of 18 F-nifene indicates promise as a PET imaging agent and thus needs further evaluation

  14. A Graphic Overlay Method for Selection of Osteotomy Site in Chronic Radial Head Dislocation: An Evaluation of 3D-printed Bone Models.

    Science.gov (United States)

    Kim, Hui Taek; Ahn, Tae Young; Jang, Jae Hoon; Kim, Kang Hee; Lee, Sung Jae; Jung, Duk Young

    2017-03-01

    Three-dimensional (3D) computed tomography imaging is now being used to generate 3D models for planning orthopaedic surgery, but the process remains time consuming and expensive. For chronic radial head dislocation, we have designed a graphic overlay approach that employs selected 3D computer images and widely available software to simplify the process of osteotomy site selection. We studied 5 patients (2 traumatic and 3 congenital) with unilateral radial head dislocation. These patients were treated with surgery based on traditional radiographs, but they also had full sets of 3D CT imaging done both before and after their surgery: these 3D CT images form the basis for this study. From the 3D CT images, each patient generated 3 sets of 3D-printed bone models: 2 copies of the preoperative condition, and 1 copy of the postoperative condition. One set of the preoperative models was then actually osteotomized and fixed in the manner suggested by our graphic technique. Arcs of rotation of the 3 sets of 3D-printed bone models were then compared. Arcs of rotation of the 3 groups of bone models were significantly different, with the models osteotomized accordingly to our graphic technique having the widest arcs. For chronic radial head dislocation, our graphic overlay approach simplifies the selection of the osteotomy site(s). Three-dimensional-printed bone models suggest that this approach could improve range of motion of the forearm in actual surgical practice. Level IV-therapeutic study.

  15. Cross-Sectional Association between Length of Incarceration and Selected Risk Factors for Non-Communicable Chronic Diseases in Two Male Prisons of Mexico City.

    Science.gov (United States)

    Silverman-Retana, Omar; Lopez-Ridaura, Ruy; Servan-Mori, Edson; Bautista-Arredondo, Sergio; Bertozzi, Stefano M

    2015-01-01

    Mexico City prisons are characterized by overcrowded facilities and poor living conditions for housed prisoners. Chronic disease profile is characterized by low prevalence of self reported hypertension (2.5%) and diabetes (1.8%) compared to general population; 9.5% of male inmates were obese. There is limited evidence regarding on the exposure to prison environment over prisoner's health status; particularly, on cardiovascular disease risk factors. The objective of this study is to assess the relationship between length of incarceration and selected risk factors for non-communicable chronic diseases (NCDs). We performed a cross-sectional analysis using data from two large male prisons in Mexico City (n = 14,086). Using quantile regression models we assessed the relationship between length of incarceration and selected risk factors for NCDs; stratified analysis by age at admission to prison was performed. We found a significant negative trend in BMI and WC across incarceration length quintiles. BP had a significant positive trend with a percentage change increase around 5% mmHg. The greatest increase in systolic blood pressure was observed in the older age at admission group. This analysis provides insight into the relationship between length of incarceration and four selected risk factors for NCDs; screening for high blood pressure should be guarantee in order to identify at risk individuals and linked to the prison's health facility. It is important to assess prison environment features to approach potential risk for developing NCDs in this context.

  16. Cross-Sectional Association between Length of Incarceration and Selected Risk Factors for Non-Communicable Chronic Diseases in Two Male Prisons of Mexico City.

    Directory of Open Access Journals (Sweden)

    Omar Silverman-Retana

    Full Text Available Mexico City prisons are characterized by overcrowded facilities and poor living conditions for housed prisoners. Chronic disease profile is characterized by low prevalence of self reported hypertension (2.5% and diabetes (1.8% compared to general population; 9.5% of male inmates were obese. There is limited evidence regarding on the exposure to prison environment over prisoner's health status; particularly, on cardiovascular disease risk factors. The objective of this study is to assess the relationship between length of incarceration and selected risk factors for non-communicable chronic diseases (NCDs.We performed a cross-sectional analysis using data from two large male prisons in Mexico City (n = 14,086. Using quantile regression models we assessed the relationship between length of incarceration and selected risk factors for NCDs; stratified analysis by age at admission to prison was performed. We found a significant negative trend in BMI and WC across incarceration length quintiles. BP had a significant positive trend with a percentage change increase around 5% mmHg. The greatest increase in systolic blood pressure was observed in the older age at admission group.This analysis provides insight into the relationship between length of incarceration and four selected risk factors for NCDs; screening for high blood pressure should be guarantee in order to identify at risk individuals and linked to the prison's health facility. It is important to assess prison environment features to approach potential risk for developing NCDs in this context.

  17. Knowledge and Perceptions Regarding Nicotine Replacement Therapy among Dental Students in Karnataka

    OpenAIRE

    Ajagannanavar, Sunil Lingaraj; Alshahrani, Obaid Abdullah; Jhugroo, Chitra; Tashery, Hamed Mohammed; Mathews, Jacob; Chavan, Khechari

    2015-01-01

    Background: Organized dentistry has recognized the role of oral health professionals in discouraging tobacco use. Unexplored level of knowledge regarding the benefits and prescription of nicotine replacement therapy (NRT) have aroused interest among us which initiated us to assess the knowledge and perception of dental students toward NRT among various dental colleges in Karnataka, South India. Materials and Methods: A questionnaire survey was done among 16 selected colleges in Karnataka. It ...

  18. 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.

  19. Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis

    Energy Technology Data Exchange (ETDEWEB)

    Gui, C.Z.; Ran, L.Y.; Li, J.P.; Guan, Z.Z. [Guiyang Medical College, Guiyang (China). Dept. of Pathology

    2010-09-15

    The purpose of the investigation is to reveal the mechanism of the decreased ability of learning and memory induced by coal burning fluorosis. Ten offspring SD rats aged 30 days, who were born from the mothers with chronic coal burning fluorosis, and ten offspring with same age from the normal mothers as controls were selected. Spatial learning and memory of the rats were evaluated by Morris Water Maze test. Cholinesterase activity was detected by photometric method. The expressions of nicotinic acetylcholine receptors (nAChRs) at protein and mRNA levels were detected by Western blotting and Real-time PCR, respectively. The results showed that in the rat offspring exposed to higher fluoride as compared to controls, the learning and memory ability declined; the cholinesterase activities in the brains were inhibited; the protein levels of alpha 3, alpha 4 and alpha 7 nAChR subunits were decreased which showed certain significant correlations with the declined learning and memory ability; and the mRNA levels of alpha 3 and alpha 4 nAChRs were decreased, whereas the alpha 7 mRNA increased. The data indicated that coal burning fluorosis can induce the decreased ability of learning and memory of rat offspring, in which the mechanism might be connected to the changed nAChRs and cholinesterase.

  20. 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.

  1. 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...

  2. 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.

  3. Effects of acute nicotine on event-related potential and performance indices of auditory distraction in nonsmokers.

    Science.gov (United States)

    Knott, Verner J; Bolton, Kiley; Heenan, Adam; Shah, Dhrasti; Fisher, Derek J; Villeneuve, Crystal

    2009-05-01

    Although nicotine has been purported to enhance attentional processes, this has been evidenced mostly in tasks of sustained attention, and its effects on selective attention and attentional control under conditions of distraction are less convincing. This study investigated the effects of nicotine on distractibility in 21 (11 males) nonsmokers with event-related potentials (ERPs) and behavioral performance measures extracted from an auditory discrimination task requiring a choice reaction time response to short- and long-duration tones, with and without imbedded deviants. Administered in a randomized, double-blind, placebo-controlled crossover design, nicotine gum (6 mg) failed to counter deviant-elicited behavioral distraction characterized by longer reaction times and increased response errors. Of the deviant-elicited ERP components, nicotine did not alter the P3a-indexed attentional switching to the deviant, but in females, it tended to diminish the automatic processing of the deviant as shown by a smaller mismatch negativity component, and it attenuated attentional reorienting following deviant-elicited distraction, as reflected by a reduced reorienting negativity ERP component. Results are discussed in relation to attentional models of nicotine and with respect to future research directions.

  4. 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.

  5. Detection of nicotine as an indicator of tobacco smoke by direct analysis in real time (DART) tandem mass spectrometry

    Science.gov (United States)

    Kuki, Ákos; Nagy, Lajos; Nagy, Tibor; Zsuga, Miklós; Kéki, Sándor

    2015-01-01

    The residual tobacco smoke contamination (thirdhand smoke, THS) on the clothes of a smoker was examined by direct analysis in real time (DART) mass spectrometry. DART-MS enabled sensitive and selective analysis of nicotine as the indicator of tobacco smoke pollution. Tandem mass spectrometric (MS/MS) experiments were also performed to confirm the identification of nicotine. Transferred thirdhand smoke originated from the fingers of a smoker onto other objects was also detected by DART mass spectrometry. DART-MS/MS was utilized for monitoring the secondhand tobacco smoke (SHS) in the air of the laboratory using nicotine as an indicator. To the best of our knowledge, this is the first report on the application of DART-MS and DART-MS/MS to the detection of thirdhand smoke and to the monitoring of secondhand smoke.

  6. 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

  7. 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

  8. 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.

  9. 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).

  10. Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains.

    Science.gov (United States)

    Kostyalik, Diána; Vas, Szilvia; Kátai, Zita; Kitka, Tamás; Gyertyán, István; Bagdy, Gyorgy; Tóthfalusi, László

    2014-11-19

    Shortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet. Chronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis. Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5-9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD. In conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence

  11. 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.

  12. Medical Expenditure for Chronic Diseases in Mexico: The Case of Selected Diagnoses Treated by the Largest Care Providers

    Science.gov (United States)

    Figueroa-Lara, Alejandro; Gonzalez-Block, Miguel Angel; Alarcon-Irigoyen, Jose

    2016-01-01

    Background Chronic diseases (CD) are a public health emergency in Mexico. Despite concern regarding the financial burden of CDs in the country, economic studies have focused only on diabetes, hypertension, and cancer. Furthermore, these estimated financial burdens were based on hypothetical epidemiology models or ideal healthcare scenarios. The present study estimates the annual expenditure per patient and the financial burden for the nine most prevalent CDs, excluding cancer, for each of the two largest public health providers in the country: the Ministry of Health (MoH) and the Mexican Institute of Social Security (IMSS). Methods Using the Mexican National Health and Nutrition Survey 2012 (ENSANUT) as the main source of data, health services consumption related to CDs was obtained from patient reports. Unit costs for each provided health service (e.g. consultation, drugs, hospitalization) were obtained from official reports. Prevalence data was obtained from the published literature. Annual expenditure due to health services consumption was calculated by multiplying the quantity of services consumed by the unit cost of each health service. Results The most expensive CD in both health institutions was chronic kidney disease (CKD), with an annual unit cost for MoH per patient of US$ 8,966 while for IMSS the expenditure was US$ 9,091. Four CDs (CKD, arterial hypertension, type 2 diabetes, and chronic ischemic heart disease) accounted for 88% of the total CDs financial burden (US$ 1.42 billion) in MoH and 85% (US$ 3.96 billion) in IMSS. The financial burden of the nine CDs analyzed represents 8% and 25% of the total annual MoH and IMSS health expenditure, respectively. Conclusions/Significance The financial burden from the nine most prevalent CDs, excluding cancer, is already high in Mexico. This finding by itself argues for the need to improve health promotion and disease detection, diagnosis, and treatment to ensure CD primary and secondary prevention. If the

  13. Medical Expenditure for Chronic Diseases in Mexico: The Case of Selected Diagnoses Treated by the Largest Care Providers.

    Science.gov (United States)

    Figueroa-Lara, Alejandro; Gonzalez-Block, Miguel Angel; Alarcon-Irigoyen, Jose

    2016-01-01

    Chronic diseases (CD) are a public health emergency in Mexico. Despite concern regarding the financial burden of CDs in the country, economic studies have focused only on diabetes, hypertension, and cancer. Furthermore, these estimated financial burdens were based on hypothetical epidemiology models or ideal healthcare scenarios. The present study estimates the annual expenditure per patient and the financial burden for the nine most prevalent CDs, excluding cancer, for each of the two largest public health providers in the country: the Ministry of Health (MoH) and the Mexican Institute of Social Security (IMSS). Using the Mexican National Health and Nutrition Survey 2012 (ENSANUT) as the main source of data, health services consumption related to CDs was obtained from patient reports. Unit costs for each provided health service (e.g. consultation, drugs, hospitalization) were obtained from official reports. Prevalence data was obtained from the published literature. Annual expenditure due to health services consumption was calculated by multiplying the quantity of services consumed by the unit cost of each health service. The most expensive CD in both health institutions was chronic kidney disease (CKD), with an annual unit cost for MoH per patient of US$ 8,966 while for IMSS the expenditure was US$ 9,091. Four CDs (CKD, arterial hypertension, type 2 diabetes, and chronic ischemic heart disease) accounted for 88% of the total CDs financial burden (US$ 1.42 billion) in MoH and 85% (US$ 3.96 billion) in IMSS. The financial burden of the nine CDs analyzed represents 8% and 25% of the total annual MoH and IMSS health expenditure, respectively. The financial burden from the nine most prevalent CDs, excluding cancer, is already high in Mexico. This finding by itself argues for the need to improve health promotion and disease detection, diagnosis, and treatment to ensure CD primary and secondary prevention. If the status quo remains, the financial burden could be higher.

  14. Medical Expenditure for Chronic Diseases in Mexico: The Case of Selected Diagnoses Treated by the Largest Care Providers.

    Directory of Open Access Journals (Sweden)

    Alejandro Figueroa-Lara

    Full Text Available Chronic diseases (CD are a public health emergency in Mexico. Despite concern regarding the financial burden of CDs in the country, economic studies have focused only on diabetes, hypertension, and cancer. Furthermore, these estimated financial burdens were based on hypothetical epidemiology models or ideal healthcare scenarios. The present study estimates the annual expenditure per patient and the financial burden for the nine most prevalent CDs, excluding cancer, for each of the two largest public health providers in the country: the Ministry of Health (MoH and the Mexican Institute of Social Security (IMSS.Using the Mexican National Health and Nutrition Survey 2012 (ENSANUT as the main source of data, health services consumption related to CDs was obtained from patient reports. Unit costs for each provided health service (e.g. consultation, drugs, hospitalization were obtained from official reports. Prevalence data was obtained from the published literature. Annual expenditure due to health services consumption was calculated by multiplying the quantity of services consumed by the unit cost of each health service.The most expensive CD in both health institutions was chronic kidney disease (CKD, with an annual unit cost for MoH per patient of US$ 8,966 while for IMSS the expenditure was US$ 9,091. Four CDs (CKD, arterial hypertension, type 2 diabetes, and chronic ischemic heart disease accounted for 88% of the total CDs financial burden (US$ 1.42 billion in MoH and 85% (US$ 3.96 billion in IMSS. The financial burden of the nine CDs analyzed represents 8% and 25% of the total annual MoH and IMSS health expenditure, respectively.The financial burden from the nine most prevalent CDs, excluding cancer, is already high in Mexico. This finding by itself argues for the need to improve health promotion and disease detection, diagnosis, and treatment to ensure CD primary and secondary prevention. If the status quo remains, the financial burden could be

  15. Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females

    International Nuclear Information System (INIS)

    Silasi, Greg; Diaz-Heijtz, Rochellys; Besplug, Jill; Rodriguez-Juarez, Rocio; Titov, Viktor; Kolb, Bryan; Kovalchuk, Olga

    2004-01-01

    Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5 Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes

  16. Patient selection and preparation strategies for the use of contrast material in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Andersen, Poul Erik

    2012-01-01

    administration of iodinated contrast media can result in contrast-induced acute kidney injury and Gadolinium can induce nephrogenic systemic fibrosis (NSF). It is important to identify these high-risk patients by means of se-creatinine/e glomerular filtration rate. The indication for contrast examination should......The prevalence of chronic kidney disease and peripheral arterial disease is increasing. Thus, it is increasingly problematic to image these patients as the number of patients needing a vascular examination is increasing accordingly. In high-risk patients with impaired kidney function, intravascular...

  17. Selective replacement of mitochondrial DNA increases the cardioprotective effect of chronic continuous hypoxia in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Neckář, Jan; Svatoňová, Anna; Weissová, Romana; Drahota, Zdeněk; Zajíčková, Pavlína; Brabcová, I.; Kolář, D.; Alánová, Petra; Vašinová, Jana; Šilhavý, Jan; Hlaváčková, Markéta; Tauchmannová, Kateřina; Milerová, Marie; Ošťádal, Bohuslav; Červenka, L.; Žurmanová, J.; Kalous, M.; Nováková, Olga; Novotný, J.; Pravenec, Michal; Kolář, František

    2017-01-01

    Roč. 131, č. 9 (2017), s. 865-881 ISSN 0143-5221 R&D Projects: GA ČR(CZ) GA13-10267S; GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 Keywords : chronic hypoxia * heart * hypertension * ischaemia–reperfusion injury * mitochondrial genome * mitochondrial permeability transition pore Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Physiology (including cytology) Impact factor: 4.936, year: 2016

  18. 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.

  19. Naturalistic assessment of demand for cigarettes, snus, and nicotine gum.

    Science.gov (United States)

    Stein, Jeffrey S; Wilson, A George; Koffarnus, Mikhail N; Judd, Michael C; Bickel, Warren K

    2017-01-01

    Behavioral economic measures of demand provide estimates of tobacco product abuse liability and may predict effects of policy-related price regulation on consumption of existing and emerging tobacco products. In the present study, we examined demand for snus, a smokeless tobacco product, in comparison to both cigarettes and medicinal nicotine. We used both a naturalistic method in which participants purchased these products for use outside the laboratory, as well as laboratory-based self-administration procedures. Cigarette smokers (N = 42) used an experimental income to purchase their usual brand of cigarettes and either snus or gum (only one product available per session) across a range of prices, while receiving all products they purchased from one randomly selected price. In a separate portion of the study, participants self-administered these products during laboratory-based, progressive ratio sessions. Demand elasticity (sensitivity of purchasing to price) was significantly greater for snus than cigarettes. Elasticity for gum was intermediate between snus and cigarettes but was not significantly different than either. Demand intensity (purchasing unconstrained by price) was significantly lower for gum compared to cigarettes, with no significant difference observed between snus and cigarettes. Results of the laboratory-based, progressive ratio sessions were generally discordant with measures of demand elasticity, with significantly higher "breakpoints" for cigarettes compared to gum and no significant differences between other study products. Moreover, breakpoints and product purchasing were generally uncorrelated across tasks. Under naturalistic conditions, snus appears more sensitive to price manipulation than either cigarettes or nicotine gum in existing smokers.

  20. The role of fear of movement and injury in selective attentional processing in patients with chronic low back pain: a dot-probe evaluation.

    Science.gov (United States)

    Roelofs, Jeffrey; Peters, Madelon L; Fassaert, Thijs; Vlaeyen, Johan W S

    2005-05-01

    The present study sought to investigate to what extent patients with chronic low back pain and pain-free control subjects selectively attend to pain-related stimuli as measured with 2 dot-probe tasks with word stimuli and pictorial stimuli. Selective attentional processing was measured by means of 3 indices: the bias index, a congruency effect, and an incongruency effect. Pain-related fear as a trait measure (Tampa Scale for Kinesiophobia [TSK]) was expected to be positively associated with all indices of selective attentional processing of pain stimuli. Results were analyzed with repeated-measures analysis of variance. An incongruency effect was found for patients and to a significantly less degree for pain-free control subjects on the dot-probe task with pictorial stimuli, indicating that pain patients have difficulty disengaging from threat pictures. Pain-related fear as a trait measure (TSK) was not associated with selective attentional processing of word and pictorial stimuli in either pain patients or control subjects. Results from the present study are discussed, and directions for future research are provided. Demonstrating difficulty to disengage from threat might be clinically relevant because patients might pay less attention to fear-disconfirming information and remain engaged in avoidance, which might eventually lead to prolonged anxiety states.

  1. PREVALENCE OF CHRONIC DISEASES IN INDIVIDUALS ASSISTED BY THE FAMILY HEALTH PROGRAM IN NITEROI, BRAZIL: EVALUATION OF SELECTION BIAS AND PROTOCOL

    Directory of Open Access Journals (Sweden)

    Rosa Maria Luiza G, Mesquita Evandro T, Jorge Antonio José L, Correia Dayse MS, Lugon Josemir R, Kang HC, Yokoo EM, Wahrlich V

    2015-07-01

    Full Text Available Background: The strategy of the Family Health Program has been used as an alternative scenario for prevalence studies. This study intended to present the protocol of the Digitalis Study (DS, prevalence study of chronic diseases, to assess sources of possible selection bias and estimate their impact on the prevalence of self-reported hypertension, diabetes, and myocardial infarction. Methods: Randomization was performed between 38 160 registered individuals with 45 to 99 years by the Family Health Program .Differences between the sources of selection bias (non-acceptance, non-attendance, substitutions were observed for gender and age. Results: Of the 1,190 residents contacted, 67.1% agreed to participate. There were 144 residents who were not randomly selected but whose participation was confirmed (substitutes. Women and individuals in the intermediate age groups and the prevalence of hypertension were higher among substitutes compared with the randomly selected individuals. Conclusion: The approach of the DS was adequate for the purposes of estimating prevalences, but there was a significant percentage of non-participation. The randomization strategy did not assume outdated records; alternative schedules for visits were not provided for; follow-up at the invitation stage was not sufficient to prevent substitutions and the inclusion of substitutes with a higher prevalence of hypertension.

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

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    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.

  3. Orthosteric and allosteric potentiation of heteromeric neuronal nicotinic acetylcholine receptors.

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    Wang, Jingyi; Lindstrom, Jon

    2018-06-01

    Heteromeric nicotinic ACh receptors (nAChRs) were thought to have two orthodox agonist-binding sites at two α/β subunit interfaces. Highly selective ligands are hard to develop by targeting orthodox agonist sites because of high sequence similarity of this binding pocket among different subunits. Recently, unorthodox ACh-binding sites have been discovered at some α/α and β/α subunit interfaces, such as α4/α4, α5/α4 and β3/α4. Targeting unorthodox sites may yield subtype-selective ligands, such as those for (α4β2) 2 α5, (α4β2) 2 β3 and (α6β2) 2 β3 nAChRs. The unorthodox sites have unique pharmacology. Agonist binding at one unorthodox site is not sufficient to activate nAChRs, but it increases activation from the orthodox sites. NS9283, a selective agonist for the unorthodox α4/α4 site, was initially thought to be a positive allosteric modulator (PAM). NS9283 activates nAChRs with three engineered α4/α4 sites. PAMs, on the other hand, act at allosteric sites where ACh cannot bind. Known PAM sites include the ACh-homologous non-canonical site (e.g. morantel at β/α), the C-terminus (e.g. Br-PBTC and 17β-estradiol), a transmembrane domain (e.g. LY2087101) or extracellular and transmembrane domain interfaces (e.g. NS206). Some of these PAMs, such as Br-PBTC and 17β-estradiol, require only one subunit to potentiate activation of nAChRs. In this review, we will discuss differences between activation from orthosteric and allosteric sites, their selective ligands and clinical implications. These studies have advanced understanding of the structure, assembly and pharmacology of heteromeric neuronal nAChRs. This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc. © 2017 The British Pharmacological Society.

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

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    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

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

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

    2017-05-15

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

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

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    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

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

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    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...

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

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    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

  9. 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.

  10. Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

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    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.

  11. 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 .

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

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    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…

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

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

    2017-10-01

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

  14. 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)

  15. 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 ...

  16. 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 ...

  17. 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 ...

  18. 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 ...

  19. Counterfeit Electronic Cigarette Products with Mislabeled Nicotine Concentrations.

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    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.

  20. Epidemiology, radiology, and genetics of nicotine dependence in COPD

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    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

  1. Racial differences in hair nicotine concentrations among smokers.

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

    2012-08-01

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

  2. 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.

  3. Identifying Chronic Conditions and Other Selected Factors That Motivate Physical Activity in World Senior Games Participants and the General Population.

    Science.gov (United States)

    Merrill, Ray M; Bowen, Elise; Hager, Ron L

    2015-01-01

    This study assesses chronic disease or disease-related conditions as motivators of physical activity. It also compares these and other motivators of physical activity between Senior Games participants (SGPs) and the general population. Analyses are based on an anonymous cross-sectional survey conducted among 666 SGPs and 177 individuals from the general population. SGPs experienced better general health and less obesity, diabetes, and depression, as well as an average of 14.7 more years of regular physical activity ( p mental health in the present, to prevent physical and cognitive decline in the future, and to increase social opportunities. The Senior Games reinforces extrinsic motivators to positively influence intrinsic promoters such as skill development, satisfaction of learning, enjoyment, and fun.

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

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    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.

  5. The burden of selected chronic non-communicable diseases and their risk factors in Malawi: nationwide STEPS survey.

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    Kelias P Msyamboza

    Full Text Available Chronic non-communicable diseases (NCDs are becoming significant causes of morbidity and mortality, particularly in sub-Saharan African countries, although local, high-quality data to inform evidence-based policies are lacking.To determine the magnitude of NCDs and their risk factors in Malawi.Using the WHO STEPwise approach to chronic disease risk factor surveillance, a population-based, nationwide cross-sectional survey was conducted between July and September 2009 on participants aged 25-64 years. Socio-demographic and behaviour risk factors were collected in Step 1. Physical anthropometric measurements and blood pressure were documented in Step 2. Blood cholesterol and fasting blood glucose were measured in Step 3.A total of 5,206 adults (67% females were surveyed. Tobacco smoking, alcohol drinking and raised blood pressure (BP were more frequent in males than females, 25% vs 3%, 30% vs 4% and 37% vs 29%. Overweight, physical inactivity and raised cholesterol were more common in females than males, 28% vs 16%, 13% vs 6% and 11% vs 6%. Tobacco smoking was more common in rural than urban areas 11% vs 7%, and overweight and physical inactivity more common in urban than rural areas 39% vs 22% and 24% vs 9%, all with p<0.05. Overall (both sexes prevalence of tobacco smoking, alcohol consumption, overweight and physical inactivity was 14%, 17%, 22%, 10% and prevalence of raised BP, fasting blood sugar and cholesterol was 33%, 6% and 9% respectively. These data could be useful in the formulation and advocacy of NCD policy and action plan in Malawi.

  6. Evaluation of the contribution of chronic skin irritation and selected compositional parameters to the tumorigenicity of petroleum middle distillates in mouse skin.

    Science.gov (United States)

    Freeman, J J; Federici, T M; McKee, R H

    1993-07-28

    Two-year skin carcinogenicity studies were conducted in C3H mice to assess the effects of irritation and selected compositional parameters on the carcinogenic potential of four petroleum liquids. Three samples (lightly refined paraffinic oil, LRPO; lightly hydrodesulfurized specialty oil, LHSO; jet fuel, JF) can be generically classified as middle distillates, i.e. distillation occurs between 350 and 700 degrees F (175-370 degrees C). The fourth sample was a Steam Cracked Gas Oil (SCGO) that distilled within the same range. In studies that assess the effects of irritation on tumorigenicity, LRPO was tested undiluted or was diluted to 50% and 25% in either mineral oil (which eliminated irritation of the skin) or toluene (which did not). Undiluted LRPO elicited tumors in 8% of the mice. Both dilution procedures eliminated tumorigenic potential. Thus, it was possible to maintain a visible level of skin irritation equivalent to that elicited by undiluted LRPO without inducing tumors. SCGO elicited a chronic irritant state grossly equivalent to LRPO but was not tumorigenic. Jet Fuel A (JF) was tested undiluted using both a standard skin painting protocol and an intermittent dosing schedule in which treatment was suspended periodically to allow skin irritation to resolve. The standard treatment protocol of JF resulted in both marked skin irritation and tumors in 44% of the mice. However, using the intermittent schedule, the tumor yield was reduced to 2%. Collectively these data demonstrate that tumor formation is not a necessary sequelae to chronic skin irritation. Conversely, prevention of a marked chronic irritant state was accompanied by decreased tumor yield. These data suggest that the chronic irritant state may be a necessary but not sufficient condition for tumor formation. In studies to assess the effects of compositional parameters, a lightly hydrodesulfurized specialty oil (LHSO) similar to LRPO but refined to have negligible levels of sulfur compounds (3 ppm

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

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    Oliveira, Hianna; Coutinho, Luccas; Higuchi, Cinthia; Noto, Cristiano; Bressan, Rodrigo; Gadelha, Ary

    2018-01-01

    Abstract Background Nicotine use is higher among patients with schizophrenia (50–98%) than in general population (25–30%). This association can reflect a non-specific liability to substance use or specific effects of tobacco on symptoms severity or side effects. Studies about nicotine use and schizophrenia symptoms dimensions are controversial. Some of them showed a relation between severe nicotine use and higher positive symptoms and others presented a correlation between lower negative symptoms and nicotine use. That is why we aimed to verify whether nicotine use is associated with symptoms dimensions in patients with schizophrenia. Methods Two hundred and seven outpatients were enrolled from the Programa de Esquizofrenia da Universidade Federal de São Paulo (PROESQ/UNIFESP). Schizophrenia diagnosis was confirmed by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Dimensional psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS) and Fagerstrom Test for Nicotine Dependence. The PANSS items were grouped in five dimensions: positive, negative, disorganized/cognitive, mood/depression and excitement/hostility. The total score of Fagerstrom Test for Nicotine Dependence was the index used for severity in nicotine dependence. We used Wilcoxon-mann- whitney test to compare the means of PANSS dimensions between nicotine users versus non nicotine use. Results The patients mean age was 36.75 (SD 10.648), 69.1% were male, 48.3% reported lifetime tobacco use and 34.3% reported current tobacco use. Lower scores on negative dimension were associated with nicotine use (W = 5642.5, p-value = 0.046, effect size = 0.446). All p-values were corrected by Bonferroni test. Tests that evaluated the relationship between nicotine use and the total PANSS score or other dimensions were not statistically significant. Discussion This study shows that nicotine use impacts negative symptoms of schizophrenia. Increase in hepatic metabolism leading

  8. Effect of nicotine and preventive role of camellia sinensis on the histomorphology of developing epiphyseal plate of thigh bone of chick

    International Nuclear Information System (INIS)

    Shan, M.; Butt, S.A.

    2014-01-01

    Objective: To determine the effect of nicotine and camellia sinensis (green tea) on the developing epiphyseal plate of thigh bone of chick. Design: Randomized controlled trial. Place and Duration of Study: Army medical college, Rawalpindi, Pakistan from April 2012 to May 2012. Material and Method: Freshly laid fertilized eggs of Fayoumi breed chick eggs were selected at zero hour of incubation. Four groups were made, group G1 was control group treated with normal saline. Experimental group G2 was treated with camellia sinensis extract (green tea), group G3 was given nicotine whereas group G4 was injected with working solution nicotine and camellia sinensis (green tea), in 0.1 ml quantity. Double exposure one at 48 hour of incubation and other at 48 hours after hatching of chicks. SPSS version 15 was used to analyze the data. Results: It was observed that the weight of chick at one month of age and weight of femur of chicks of nicotine treated groups G3 and group G4 were reduced in comparison to control group G1. Mean number of cells in hypertrophy zone of developing epiphyseal plate of thigh bone were reduced of nicotine treated groups in comparison to control group. Conclusion: Camellia sinensis (green tea) helped to reduce the harmful effects of nicotine treated group but cannot reverse the oxidative injury. (author)

  9. 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.

  10. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  11. 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.

  12. 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.

  13. 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...

  14. 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....

  15. 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....

  16. Adolescent Social Stress Increases Anxiety-like Behavior and Alters Synaptic Transmission, Without Influencing Nicotine Responses, in a Sex-Dependent Manner.

    Science.gov (United States)

    Caruso, Michael J; Crowley, Nicole A; Reiss, Dana E; Caulfield, Jasmine I; Luscher, Bernhard; Cavigelli, Sonia A; Kamens, Helen M

    2018-03-01

    Early-life stress is a risk factor for comorbid anxiety and nicotine use. Because little is known about the factors underlying this comorbidity, we investigated the effects of adolescent stress on anxiety-like behavior and nicotine responses within individual animals. Adolescent male and female C57BL/6J mice were exposed to chronic variable social stress (CVSS; repeated cycles of social isolation + social reorganization) or control conditions from postnatal days (PND) 25-59. Anxiety-like behavior and social avoidance were measured in the elevated plus-maze (PND 61-65) and social approach-avoidance test (Experiment 1: PND 140-144; Experiment 2: 95-97), respectively. Acute nicotine-induced locomotor, hypothermic, corticosterone responses, (Experiment 1: PND 56-59; Experiment 2: PND 65-70) and voluntary oral nicotine consumption (Experiment 1: PND 116-135; Experiment 2: 73-92) were also examined. Finally, we assessed prefrontal cortex (PFC) and nucleus accumbens (NAC) synaptic transmission (PND 64-80); brain regions that are implicated in anxiety and addiction. Mice exposed to adolescent CVSS displayed increased anxiety-like behavior relative to controls. Further, CVSS altered synaptic excitability in PFC and NAC neurons in a sex-specific manner. For males, CVSS decreased the amplitude and frequency of spontaneous excitatory postsynaptic currents in the PFC and NAC, respectively. In females, CVSS decreased the amplitude of spontaneous inhibitory postsynaptic currents in the NAC. Adolescent CVSS did not affect social avoidance or nicotine responses and anxiety-like behavior was not reliably associated with nicotine responses within individual animals. Taken together, complex interactions between PFC and NAC function may contribute to adolescent stress-induced anxiety-like behavio