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1
Polet, Grégoire. "Nicosie mon amour." Méditerranée, no. 129 (November 1, 2017): 37–41. http://dx.doi.org/10.4000/mediterranee.9011.
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Colcombet, François. "Nicosie, une capitale déchirée." Après-demain N°51,NF, no. 3 (2019): 18. http://dx.doi.org/10.3917/apdem.051.0018.
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Deliolanes, Dimitri. "L'axe Athènes-Nicosie-Tel-Aviv." Outre-Terre 31, no. 1 (2012): 321. http://dx.doi.org/10.3917/oute.031.0321.
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Blokh, Alexandre. "Le Leventis, musée municipal de Nicosie." Museum International (Edition Francaise) 46, no. 3 (2009): 51–53. http://dx.doi.org/10.1111/j.1755-5825.1994.tb00621.x.
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Claverie, Pierre-Vincent. "La succession de l'archevêque Gilles de Nicosie." Le Moyen Age CVIII, no. 2 (2002): 333. http://dx.doi.org/10.3917/rma.082.0333.
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Nicolaou- Michaelidou, Ino. "Deux cippes funéraires du musée de Nicosie, Chypre." Cahiers du Centre d'Etudes Chypriotes 27, no. 1 (1997): 145–48. http://dx.doi.org/10.3406/cchyp.1997.1328.
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Maheras, Panagiotis, and A. Arseni-Papadimitriou. "Variations des températures durant la dernière période séculaire à Nicosie (Chypre)." Méditerranée 63, no. 1 (1988): 35–41. http://dx.doi.org/10.3406/medit.1988.2526.
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Papayiannis, Georges, and Pierre-Yves Péchoux. "L'évolution de la frange périurbaine de Nicosie (Chypre) de 1931 à 1992." Méditerranée 77, no. 1 (1993): 49–53. http://dx.doi.org/10.3406/medit.1993.2806.
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Vaivre, Jean-Bernard de. "Le tympan du portail central de la cathédrale Sainte-Sophie de Nicosie (information)." Comptes-rendus des séances de l année - Académie des inscriptions et belles-lettres 145, no. 2 (2001): 1031–42. http://dx.doi.org/10.3406/crai.2001.16316.
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Arbel, Benjamin. "Sauterelles et mentalités : le cas de la Chypre vénitienne." Annales. Histoire, Sciences Sociales 44, no. 5 (1989): 1057–74. http://dx.doi.org/10.3406/ahess.1989.283642.
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Nicosie, août 1509. Couché malade dans sa résidence, Antonio Da Lezze, conseiller du gouverneur de Chypre au nom de la Serenissime, est réveillé par ce qui semble être un tumulte populaire. En effet, le peuple de la capitale veut du pain et le fait savoir bruyamment.En règle générale, le pain ne manque pas à Chypre. Vénitienne de facto depuis 1473, de jure depuis 1489, l'île est même, traditionnellement, l'un des fournisseurs en grain de Venise, qu'elle a sauvée à plusieurs reprises de la famine. Or voici qu'à l'heure où la métropole connaît l'un des tournants les plus dramatiques de son histoire — la guerre de la Ligue de Cambrai —, sa plus grosse colonie est incapable de venir à son secours.
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Anastiasiadès, Nicos. "Cérémonie officielle au palais présidentiel, Nicosie, 14 mai 2015 : Discours de M. Nicos Anastiasiadès, Président de la République de Chypre." Cahiers du Centre d'Etudes Chypriotes 44, no. 1 (2014): 45–50. http://dx.doi.org/10.3406/cchyp.2014.1536.
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Cassimatis, Hélène. "Colloque archéologique international "Chypre entre l'Orient et 1' Occident", Nicosie 8 -I4 septembre 1985." Cahiers du Centre d'Etudes Chypriotes 4, no. 1 (1985): 61–73. http://dx.doi.org/10.3406/cchyp.1985.1187.
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François, Véronique. "Poteries des fosses dépotoirs du site de l’Archiepiskopi à Nicosie (fin XIIe‑XIVe siècles)." Bulletin de Correspondance Hellénique, no. 141.2 (December 1, 2017): 821–95. http://dx.doi.org/10.4000/bch.585.
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François, Véronique. "Fragments d’histoire II : la vaisselle de table et du quotidien à Nicosie au lendemain de la conquête ottomane." Bulletin de Correspondance Hellénique, no. 141.1 (June 1, 2017): 353–87. http://dx.doi.org/10.4000/bch.552.
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Trélat, Philippe, and Hesperia Iliadou. "Localiser les marchés. Les activités artisanales et commerciales à Nicosie durant les périodes latine et ottomane / Tracing the market place : Commercial and artisan activity in Nicosia between the Latin and Ottoman eras." Cahiers du Centre d'Etudes Chypriotes 41, no. 1 (2011): 299–328. http://dx.doi.org/10.3406/cchyp.2011.1114.
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Triantara, Yoan Asri, Inggit Almira, Sarwan Adi Kusumo, Muhammad Fajar, Dicky Darmawan, and Dwi Winarni. "The Comparison Effect of Electrical Cigarrete and Conventional Cigarrete Smoke toward White Rat’s (Rattus norvegicus) Lung Histopathology." Jurnal Respirologi Indonesia 39, no. 2 (2019): 88–91. http://dx.doi.org/10.36497/jri.v39i2.52.
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Background: The number of cigarettes smoked per day has an average of 12,3% of cigarettes in 2013. The increase of the conventional cigarettes price in 2016 made some conventional smokers switch to electrical cigarettes because more safety than conventional One of the indicators of pulmonary damage is the increase of alveolar macrophage that cause pulmonary structural change triggered by substances in the cigarette.
 Methods: Thirty two of white rat were divided into four groups (control, conventional cigarette, electrical cigarette with 0 miligram (mg) nicotine, and electrical cigarette with 3 mg nicotine) and were exposed for 35 days (30x2 minutes; in the morning and evening).
 Results: The group exposed to conventional cigarette smoke has the highest average number of macrophages than the cigarette smoke group with nicotin levels of 0 mg, electric cigarette with 3 mg nicotine and control. Brown Forsythe test continued with Games-Howell post hoc test indicates that there are significant mean difference between each group except between group exposed to electric cigarette smoke with 3 mg nicotine and exposed to conventional cigarette smoke. Based on the indicator assumption of lymphoid infiltration and thickening and fusion of the alveolar, the smoke of conventional cigarette and electric cigarette with 3 mg nicotine caused more histopathological damage to the white rat’s lungs than of conventional cigarette than the smoke of electric cigarette with 0 mg nicotine and those in the control group.
 Conclusion: The exposure of conventional cigarette smoke caused the highest damage to Rattus norvegicus’ pulmo according to macrophage alveolar and histopathological indicator, but not significantly different with the exposure of electrical cigarette with 3 mg nicotine. The exposure of electrical cigarette with 0 mg nicotine caused minor damage equals to control group based on histopathological indicator. (J Respir Indo 2019; 39(2))
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GRIVAUD, Gilles. "La Révolution française et l'hellénisme moderne, Athènes, Centre de Recherche Néohellenique, 1989, 600 p. / Paul et Anna Fouradier Duteil, Chypre au temps de la Révolution française d'après les dépêches du consul de France à Larnaca, Nicosie." CEMOTI, no. 12 (June 1, 1991): 235–37. http://dx.doi.org/10.4000/cemoti.386.
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Zetter, Roger. "Nicosia." Cities 2, no. 1 (1985): 24–33. http://dx.doi.org/10.1016/0264-2751(85)90059-9.
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TUNÇAY ÇAĞATAY, Seda, Gülşah ÇALIK KOÇ, Fereshteh REZAEİ, Özlem DARCANSOY İŞERI, Feride İffet ŞAHIN, and Mehmet HABERAL. "Evaluation of production conditions of tomato grafted with different tobacco rootstocks and determining nicotine content and quality of fruit." Acta agriculturae Slovenica 115, no. 2 (2020): 297. http://dx.doi.org/10.14720/aas.2020.115.2.1244.
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<p>This study aimed to investigate the effects of grafting tomato on different tobacco rootstocks on quality factors and nicotine content. The commercial variety (Solanum lycopersicum ‘H2274’) (BIOTECH) of the tomato was used as the scion plant, and six different tobacco (Nicotiana tabacum L.) rootstocks were used: Taşova, Tekel, Muş, Samsun, Dişbudak, Hasankeyf cultivars. Cleft grafting method was used in all plants. Yield of non-grafted and grafted plants grown in open-field conditions was calculated, and there was a significant increase in yield in grafted tomatoes compared to non-grafted tomatoes. There was significantly increased lycopene and β-carotene levels (mg kg-1), especially in ‘Tekel’, ‘Taşova’, ‘Samsun’, and ‘Hasankeyf’ tobacco grafts. There was a statistically significant difference between grafted and non-grafted plants according to 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical retention capacities and total phenol (TP) values. Evaluation of quality determinants including pH values, titratable acidity values (citric acid %), soluble solid content (SSC)(oBrix) , fruit size ratios, showed that tomatoes grafted with ‘Muş’ tobacco rootstock were of higher quality. There was no significant difference between grafted and non-grafted plants according to nicotine analysis of the tobacco-grafted tomatoes, and due to acceptable ranges of nicotin level on tobacco grafted tomato plants were considered to be suitable for consumption. It could be concluded that grafting practices have significantly positive effects on tomato yield and quality.<br /><br /></p>
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CIOLAN, Ioana Monica. "Nicotine Craving and Cue-Exposure Therapy." Logos Universality Mentality Education Novelty. Section: SOCIAL SCIENCES 04, no. 01 (2015): 79–87. http://dx.doi.org/10.18662/lumenss.2015.0401.07.
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Chagas, Ana Maria, Zuleica Tabarelli, Ruben Boelter, Lisandre Kipper, Rejane Mello Flores, and José Antônio Aguilar Vaca. "Efeito do hexametônio sobre a contratilidade de músculo liso de cobaios provocada pelo extrato aquoso do fungo Ramaria Flavo Brunnescens." Ciência e Natura 8, no. 8 (1986): 67. http://dx.doi.org/10.5902/2179460x25441.
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Animals poisoning by ingestion of Ramaria flava brunnescens fungus found in Eucalipto groves is common in Southern Brazil. This poisoning does not have an effective antidote yet and it is common to avoid the toxicity by removing the animals from these fields or by using atropin when fungus intoxication signals appear. Present work was reallized to elucidate the manner and place of action of this fungus aqueous extract on isolated guinea pig ileum. For this purpose, we used Magnus Bath and strain transducer to Physiograph connect. Experiences were realized with 18 ileum tested with 10 mcg Nicotine. 24.600 mcg Ramaria flavo brunnescens fungus' aqueous extract and 30 mcg Hexametonium. Those concentrations were choosen from pilot experiences. The results showed that uses of this fungus extract provokes smooth muscle contraction similar to that of nicotin, the difference between both occurs due to Hexametone blockade impossibility. This fact suggests that the death mechanism of animals that eat this fungus is not due to ganglionar stimulation.
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Köksald, Esra, Zihni Turkan, and Buket Asilsoy. "Landscape in Historical Urban Textures: “Walled City Nicosia From the Past To The Present”." European Journal of Sustainable Development 10, no. 2 (2021): 127–46. http://dx.doi.org/10.14207/ejsd.2021.v10n2p127.
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Historical urban textures are the whole of the open and closed public spaces with the buildings and transportation axis, shaped by the cultural heritages of cities. One of the most important elements in historical urban textures, bringing dwellers with nature, and giving life to the city, are landscape spaces. The capital of Cyprus, Nicosia, also has a very rich historical texture. Within this context, the aim of this study is to examine the landscape of the historical urban texture of Nicosia from the past to the present, within the whole of various cultural periods including the present day status. Therefore, the development of Nicosia through the historical process is given right after the introduction. After the introduction, landscape of walled city of Nicosia was examined through the historical periods: Lusignan Period, Venetian Period, Ottoman Period, British Period, Republic of Cyprus Period, and the present day period, TRNC Period.
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Carstens, E., Nicole Kuenzler, and H. O. Handwerker. "Activation of Neurons in Rat Trigeminal Subnucleus Caudalis by Different Irritant Chemicals Applied to Oral or Ocular Mucosa." Journal of Neurophysiology 80, no. 2 (1998): 465–92. http://dx.doi.org/10.1152/jn.1998.80.2.465.
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Carstens, E., Nicole Kuenzler, and H. O. Handwerker. Activation of neurons in rat trigeminal subnucleus caudalis by different irritant chemicals applied to oral or ocular mucosa. J. Neurophysiol. 80: 465–492, 1998. To investigate the role of trigeminal subnucleus caudalis in neural mechanisms of irritation, we recorded single-unit responses to application of a variety of irritant chemicals to the tongue or ocular mucosa in thiopental-anesthetized rats. Recordings were made from wide dynamic range (WDR) and nociceptive-specific units in superficial layers of the dorsomedial caudalis (0–3 mm caudal to obex) responsive to mechanical stimulation and noxious heating of the ipsilateral tongue (“tongue” units) and from WDR units in ventrolateral caudalis (0–2 caudal to obex) responsive to mechanical and noxious thermal stimulation of cornea-conjunctiva and frequently also surrounding skin (“cornea-conjunctival” units). The following chemicals were delivered topically (0.1 ml) onto the dorsal anterior tongue or instilled into the ipsilateral eye: capsaicin (0.001–1% = 3.3 × 10−2 to 3.3 × 10−5 M), ethanol (15–80%), histamine (0.01–10% = 9 × 10−1 to 9 × 10−4 M), mustard oil (allyl-isothiocyanate, 4–100% = 4 × 10−1 to 10 M), NaCl (0.5–5 M), nicotine (0.01–10% = 6 × 10−1 to 6 × 10−4 M), acidified phosphate buffer (pH 1–6), piperine (0.01–1% = 3.5 × 10−2 to 3.5 × 10−4 M), serotonin (5-HT; 0.3–3% = 1.4 × 10−1 to 1.4 × 10−2 M), and carbonated water. The dose-response relationship and possible tachyphylaxis were tested for each chemical. Of 32 tongue units, 31 responded to one or more, and frequently all, chemicals tested. The population responded to 75.3% of the various chemicals tested (≤10 per unit). The incidence of responses was independent of the order of chemicals tested, except for capsaicin, which reduced subsequent responses. Responses to histamine, nicotine, 5-HT, and ethanol had a more rapid onset and shorter duration compared with capsaicin, acid, and mustard oil. Responses to all chemicals increased in a dose-related manner. Successive responses to repeated application decreased significantly for nicotine, 5-HT, capsaicin, and piperine. Spontaneous firing increased significantly 5–10 min after initial application of capsaicin. Of 31 corneal-conjunctival units, 29 responded to one or more chemicals, and the population responded to 65% of all chemicals tested. Responses increased in a dose-related manner for all chemicals, and successive responses decreased significantly for histamine, nicotine, ethanol, acid, and capsaicin. Responses of tongue units to histamine and nicotine were reduced significantly by ceterizine (H1 antagonist) and mecamylamine, respectively. Mecamylamine also significantly reduced responses of corneal-conjunctival units to nicotine. Different classes of irritant chemicals contacting the oral or ocular mucosa can activate individual sensory neurons in caudalis, presumably via independent peripheral transduction mechanisms. Multireceptive units with input from the tongue or cornea-conjunctiva exhibited a similar spectrum of excitability to different irritant chemicals. Such neurons would not be capable of discriminating among different chemically evoked irritant sensations but could contribute to a common chemical sense.
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Turkan, Zihni. "Sustainability in the Formation and Development of Historical Cities: “Nicosia Historical City Texture”." European Journal of Sustainable Development 9, no. 2 (2020): 250–62. http://dx.doi.org/10.14207/ejsd.2020.v9n2p250.
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The formation of the historical city texture of Nicosia, the capital of Cyprus, began during the Lusignan Period. St. Sophia Cathedral and St. Catherine Church, which have an important place in the formation of the texture, are two of the few works of art still surviving today. Being a period of destruction for the city, in general, The Venetian Period provided the city walls to Nicosia which still surround the historical texture. The Ottoman Period brought a change to the historical city texture and Islamic culture and Turkish Architectural construction style replaced the Christian cultures. A number of architectural works from this period, still existing within the walled city of Nicosia, provided a great contribution to the formation and development of the present day texture, as well as for its sustainability. The British Period is one which brought novelty to the city texture of Nicosia. With demolition of historical works and changes in the street and square dimensions, British Colonial Architecture displays the traces of the recent past. The administrative buildings constructed in place of the demolished Lusignan Palace, still serve at present. With the beginning of the Period of the Republic in 1960, Nicosia underwent a fast process of development as an important capital in the Middle East. The traditional visuality in the city texture left its place to contemporary constructions and formations. The inter-communal conflicts, which started in 1964 on the other hand, negatively affected the formation and development of the city texture, and there was a period of stagnation until the 70s. The new developments observed since the 70s and the insufficiency of precautions to protect historical texture, caused a deterioration the city texture. With the position of an open-air museum, Nicosia with its history of over twenty-five centuries has a very rich historical city texture with the legacies of various cultures which reigned over Cyprus and is sustainable in the present, and is therefore an important cultural and touristic center Keywords: Cyprus, Nicosia, Historical City Texture, Walled City, Sustainability.
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Mehmet Ali, Aydın. "Women of Nicosia." European Journal of English Studies 19, no. 3 (2015): 368–69. http://dx.doi.org/10.1080/13825577.2015.1091227.
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Uzunoğlu, Kozan, and Semra Sema Uzunoğlu. "The Importance of Pedestrianization in Cities- Assessment of Pedestrianized Streets in Nicosia Walled City." European Journal of Sustainable Development 9, no. 2 (2020): 589–614. http://dx.doi.org/10.14207/ejsd.2020.v9n2p589.
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approach in recent years. One of these cities which is the last divided capital city and one of the most important cultural heritages of the Mediterranean region in the island of Cyprus is the Nicosia Walled City. Within this study, the existing situation of pedestrianized areas in the Walled City in north Nicosia were examined. In literature review part, the importance of pedestrianization, reasons and benefits of pedestrianization, examples of pedestrianized areas/streets around the world are reviewed. The pedestrianized streets/areas in the north Nicosia Walled City were examined on-site, photographed, their current status was revealed and evaluated according to determined criteria. Each street/area was evaluated in terms of functions in the street, mobility, accessibility by car or public transportation, social/community activities, economic development and quality of physical environment. When the old city of Nicosia is analyzed in the context of these criteria, it has been observed that the pedestrianized areas have an increasing social, cultural and economical contribution to the city. In addition to its historical features, the places and activities that attract the people especially young population and tourists, bring life to this region. In terms of environmental aspects, visual incompatibilities were observed even in the streets where pedestrianization studies have been carried out recently. There are also problems about vehicle and pedestrian traffic that affect users. The study was completed by making suggestions at the end of the study. Keywords: pedestrianized streets, pedestrianized squares, Nicosia Walled City, Cyprus
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Akrodou, Yawo Mawuli. "CYP2A6 Polymorphisms May Strengthen Individualized Treatment for Nicotine Dependence." Scientifica 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/491514.
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EachCYP2A6gene variant metabolizes nicotine differently depending on its enzymatic activities. The normal nicotine metabolizerCYP2A6*1Ais associated with high scores of nicotine dependence (5–10) on the Fagerström Test for Nicotine Dependence (FTND) scale because it encodes for enzymes that catalyze nicotine 100%. Slow nicotine metabolizers (i.e.,CYP2A6*1H,CYP2A6*4A,CYP2A6*9, andCYP2A6*12A) are associated with underrated nicotine metabolizing activity (50%–75%), linking them to low scores for nicotine dependence (0–4) on the FTND scale. In a clinical trial involving the use of bupropion, people who were carriers of slow nicotine metabolizers were found to have a tendency to maintain abstinence 1.7 times longer than people with normal nicotine metabolizers. An overview of CYP2A6 polymorphism enzymatic activities in nicotine dependence etiology and treatment revealed that slow nicotine metabolizers may strengthen the individualized treatment of nicotine dependence.
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Ganas, Petra, and Roderich Brandsch. "Uptake of l-nicotine and of 6-hydroxy-l-nicotine by Arthrobacter nicotinovorans and by Escherichia coli is mediated by facilitated diffusion and not by passive diffusion or active transport." Microbiology 155, no. 6 (2009): 1866–77. http://dx.doi.org/10.1099/mic.0.028688-0.
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The mechanism by which l-nicotine is taken up by bacteria that are able to grow on it is unknown. Nicotine degradation by Arthrobacter nicotinovorans, a Gram-positive soil bacterium, is linked to the presence of the catabolic megaplasmid pAO1. l-[14C]Nicotine uptake assays with A. nicotinovorans showed transport of nicotine across the cell membrane to be energy-independent and saturable with a K m of 6.2±0.1 μM and a V max of 0.70±0.08 μmol min−1 (mg protein)−1. This is in accord with a mechanism of facilitated diffusion, driven by the nicotine concentration gradient. Nicotine uptake was coupled to its intracellular degradation, and an A. nicotinovorans strain unable to degrade nicotine (pAO1−) showed no nicotine import. However, when the nicotine dehydrogenase genes were expressed in this strain, import of l-[14C]nicotine took place. A. nicotinovorans pAO1− and Escherichia coli were also unable to import 6-hydroxy-l-nicotine, but expression of the 6-hydroxy-l-nicotine oxidase gene allowed both bacteria to take up this compound. l-Nicotine uptake was inhibited by d-nicotine, 6-hydroxy-l-nicotine and 2-amino-l-nicotine, which may indicate transport of these nicotine derivatives by a common permease. Attempts to correlate nicotine uptake with pAO1 genes possessing similarity to amino acid transporters failed. In contrast to the situation at the blood–brain barrier, nicotine transport across the cell membrane by these bacteria was not by passive diffusion or active transport but by facilitated diffusion.
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Steiner, Alexandre A., Daniela L. Oliveira, Jennifer L. Roberts, Scott R. Petersen, and Andrej A. Romanovsky. "Nicotine administration and withdrawal affect survival in systemic inflammation models." Journal of Applied Physiology 105, no. 4 (2008): 1028–34. http://dx.doi.org/10.1152/japplphysiol.90619.2008.
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How different regimens of nicotine administration and withdrawal affect systemic inflammation is largely unknown. We studied the effects of chronic and acute nicotine administration and of nicotine withdrawal on the outcome of aseptic and septic systemic inflammation. Male C57BL/6 mice were implanted with subcutaneous osmotic pumps (to deliver nicotine) and intrabrain telemetry probes (to measure temperature). Aseptic inflammation was induced by lipopolysaccharide (40 mg/kg ip); sepsis was induced by cecal ligation and puncture. The chronic nicotine administration group received nicotine (28 mg·kg−1·day−1) for 2 wk before the induction of inflammation and continued receiving nicotine until the end of the experiment; the acute nicotine administration group received saline for 2 wk and nicotine thereafter; the nicotine withdrawal group received nicotine for 2 wk and saline thereafter; and the no-nicotine group was infused with saline throughout the experiment. Compared with no nicotine, the chronic nicotine administration did not affect survival in either model of inflammation, possibly due to the development of nicotine tolerance. The acute nicotine administration increased the survival rate in aseptic inflammation from 11 to 33% (possibly by suppressing inflammation) but worsened the outcome of sepsis (possibly because the suppression of inflammation promoted microbial proliferation). Oppositely to acute nicotine, nicotine withdrawal increased the survival rate in sepsis from 18 to 40%. The effects on survival were not due to changes in body temperature. We conclude that acute nicotine administration and nicotine withdrawal affect survival in systemic inflammation and that these effects strongly depend on whether inflammation is aseptic or septic.
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Perfetti, TA, AB Norman, BM Gordon, et al. "The Transfer of Nicotine from Nicotine Salts to Mainstream Smoke." Beiträge zur Tabakforschung International/Contributions to Tobacco Research 19, no. 3 (2000): 141–58. http://dx.doi.org/10.2478/cttr-2013-0702.
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AbstractTransfer of nicotine to mainstream smoke was measured for Reference cigarettes made with the addition of 20 -40 mg of seven different nicotine salts, d- and l-nicotine and N’-formylnornicotine. Regression analysis of the nicotine yields from these cigarettes as a function of the nicotine content of the tobacco rods indicated an average nicotine transfer efficiency (17.5%), similar to that found for a separate series of cigarettes made with single-grade tobacco materials (16.2%). Analysis of the enantiomeric purity of the smoke nicotine from the cigarettes made with added nicotine salts and neat nicotine showed no evidence of conversion between l- and d-nicotine during the smoking process. The cigarette made with added N’-formylnornicotine showed no evidence of additional nicotine transfer attributable to reduction of this compound to nicotine. A third series of cigarettes were made with varying levels of d- and l-nicotine added to a tobacco blend and to reconstituted tobacco to further investigate transfer efficiency of the enantiomers. Regression analysis indicated no statistically significant difference between transfer efficiencies of d- and l-nicotine. These results suggest that nicotine salts and d- and l-nicotine transfer to smoke at the same efficiency. However, transfer efficiency of either compound was lower when applied to reconstituted tobacco (9.7%) than when applied to the Reference tobacco blend (15.3%). The thermal stabilities of nicotine salts have little bearing on efficiency of transfer to smoke or on racemization between d- and l-nicotine. Formation of d-nicotine in mainstream smoke via reduction of N’-formylnornicotine does not appear to occur.
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Perfetti, TA, BM Gordon, WM Coleman III, and WT Morgan. "Determination of the Transfer Efficiency of d-Nicotine to Mainstream Smoke." Beiträge zur Tabakforschung International/Contributions to Tobacco Research 19, no. 5 (2001): 237–44. http://dx.doi.org/10.2478/cttr-2013-0710.
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AbstractExperiments were conducted to independently determine the mainstream smoke transfer efficiency of d-nicotine and l-nicotine. Two types of cigarettes (University of Kentucky 2R1 reference cigarette and a cigarette prepared from reconstituted sheet material, TS1) were employed in the study. A chiral-gas chromatography-selected ion monitoring-mass selective detection analysis was used to separate and determine d- and l-nicotine. The two types of cigarettes were injected with varying levels of d- or l-nicotine (0-20 mg). The tobacco was removed from the nicotine-injected cigarettes and analyzed for total nicotine and d- and l-nicotine. The cigarettes were smoked under FTC (Federal Trade Commission) conditions, and the Cambridge pad extracts were analyzed for total nicotine and d- and l-nicotine. The total nicotine transfer efficiency and the transfer efficiencies of d- and l-nicotine were determined. Nicotine transfer efficiency is dependent on the type of tobacco employed in a blend and the configuration of the cigarette. As a result, the total nicotine transfer efficiency for the 2R1 cigarettes was different than for the TS1 cigarettes. Likewise, the independently measured transfer efficiencies for d- and l-nicotine were different between the two cigarettes. The transfer efficiencies of d- and l-nicotine were not found to be different within a cigarette type. The average transfer efficiency for d-nicotine in a 2R1 cigarette was determined to be 19.25%. The average transfer efficiency for l-nicotine in a 2R1 cigarette was 16.05%. The average transfer efficiency for d-nicotine in a TS1 cigarette was 10.15% and 10.65% for l-nicotine. These differences between d- and l-nicotine were determined not to be statistically significant and are of no practical consequence.
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Aldeek, Fadi, Nicholas McCutcheon, Cameron Smith, John H. Miller, and Timothy L. Danielson. "Dissolution Testing of Nicotine Release from OTDN Pouches: Product Characterization and Product-to-Product Comparison." Separations 8, no. 1 (2021): 7. http://dx.doi.org/10.3390/separations8010007.
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In recent years, oral tobacco-derived nicotine (OTDN) pouches have emerged as a new oral tobacco product category. They are available in a variety of flavors and do not contain cut or ground tobacco leaf. The on!® nicotine pouches fall within this category of OTDN products and are currently marketed in seven (7) flavors with five (5) different nicotine levels. Evaluation of the nicotine release from these products is valuable for product assessment and product-to-product comparisons. In this work, we characterized the in vitro release profiles of nicotine from the 35 varieties of on!® nicotine pouches using a fit-for-purpose dissolution method, employing the U.S. Pharmacopeia flow-through cell dissolution apparatus 4 (USP-4). The nicotine release profiles were compared using the FDA’s Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms. The cumulative release profiles of nicotine show a dose dependent response for all nicotine levels. The on!® nicotine pouches exhibit equivalent percent nicotine release rates for each flavor variant across all nicotine levels. Furthermore, the nicotine release profiles from on!® nicotine pouches were compared to a variety of other commercially available OTDN pouches and traditional pouched smokeless tobacco products. The percent nicotine release rates were found to be dependent on the product characteristics, showing similarities and differences in the nicotine release profiles between the on!® nicotine pouches and other compared products.
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Aldeek, Fadi, Nicholas McCutcheon, Cameron Smith, John H. Miller, and Timothy L. Danielson. "Dissolution Testing of Nicotine Release from OTDN Pouches: Product Characterization and Product-to-Product Comparison." Separations 8, no. 1 (2021): 7. http://dx.doi.org/10.3390/separations8010007.
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In recent years, oral tobacco-derived nicotine (OTDN) pouches have emerged as a new oral tobacco product category. They are available in a variety of flavors and do not contain cut or ground tobacco leaf. The on!® nicotine pouches fall within this category of OTDN products and are currently marketed in seven (7) flavors with five (5) different nicotine levels. Evaluation of the nicotine release from these products is valuable for product assessment and product-to-product comparisons. In this work, we characterized the in vitro release profiles of nicotine from the 35 varieties of on!® nicotine pouches using a fit-for-purpose dissolution method, employing the U.S. Pharmacopeia flow-through cell dissolution apparatus 4 (USP-4). The nicotine release profiles were compared using the FDA’s Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms. The cumulative release profiles of nicotine show a dose dependent response for all nicotine levels. The on!® nicotine pouches exhibit equivalent percent nicotine release rates for each flavor variant across all nicotine levels. Furthermore, the nicotine release profiles from on!® nicotine pouches were compared to a variety of other commercially available OTDN pouches and traditional pouched smokeless tobacco products. The percent nicotine release rates were found to be dependent on the product characteristics, showing similarities and differences in the nicotine release profiles between the on!® nicotine pouches and other compared products.
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Thompson, Gwendolyn H., and Dee A. Hunter. "Nicotine Replacement Therapy." Annals of Pharmacotherapy 32, no. 10 (1998): 1067–75. http://dx.doi.org/10.1345/aph.17382.
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OBJECTIVE: To review the literature on nicotine dependence, nicotine pharmacology, health consequences associated with the use of nicotine, and nicotine replacement therapies used to aid smokers who are nicotine dependent. DATA SOURCES: A review of articles, book bibliographies, and published studies identified by a search of the MEDLINE database from 1982 to 1996 on nicotine dependence, nicotine addiction, nicotine withdrawal, smoking, smoking cessation, smoking intervention, nicotine pharmacology, nicotine pharmacokinetics, nicotine pharmacodynamics, and nicotine replacement therapies. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria were published randomized, double-blind trials of at least 12 weeks' duration, meta-analyses, and panel consensus guidelines. DATA SYNTHESIS: Cigarette smoking and tobacco use have met the surgeon general's primary criteria as well as additional criteria for drug dependence. Drug dependence requires that the drug produce psychoactive effects. Nicotine has been identified as the cause of tobacco dependence. First, nicotine provides positive reinforcement by stimulating nicotinic receptors to promote high self-administration rates. Second, nicotine causes a negative reinforcement in the form of withdrawal symptoms when nicotine is withheld after chronic use. Nicotine replacement therapy reduces the severity of withdrawal symptoms in smokers abstaining from tobacco. Nicotine replacement therapy allows the smoker to focus on psychosocial aspects of tobacco abstinence while receiving relief from withdrawal symptoms. The long-term effectiveness and health benefits of nicotine replacement therapy coupled with nonpharmacologic approaches have been clearly established. Smoking cessation has received wide attention from the public and medical communities; it is complex and has several interwoven factors to be considered. The psychological, behavioral, and physical components have to be understood before designing a treatment plan. The most successful approaches to smoking cessation involve multicomponent, multisession behavioral treatment programs as a foundation coupled with pharmacologic intervention. Pharmacists can play a key role in initiating behavior change and ensuring the safe and proper use of nicotine replacement in order to produce the desired outcome. CONCLUSIONS: The optimum choice in nicotine replacement depends on the individual's needs and coping abilities. Individualized nicotine replacement coupled with nonpharmacologic interventions produces the highest rate of success for abstinence from nicotine.
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Morean, Meghan E., Olivia A. Wackowski, Thomas Eissenberg, Cristine D. Delnevo, and Suchitra Krishnan-Sarin. "Adolescents and Young Adults Have Difficulty Understanding Nicotine Concentration Labels on Vaping Products Presented as mg/mL and Percent Nicotine." Nicotine & Tobacco Research 23, no. 8 (2021): 1389–97. http://dx.doi.org/10.1093/ntr/ntab007.
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Abstract Introduction E-cigarette e-liquid nicotine concentrations typically are labeled as mg/mL or percent nicotine. We examined whether these metrics accurately convey nicotine strength to young e-cigarette users and if youth can compare concentrations presented in mg/mL and percent nicotine. Aims and Methods Eight hundred and twenty-one adolescent and young adult e-cigarette users participated in the survey. Participants rated nicotine concentration strengths presented as mg/mL (0–60 mg/mL) and percent nicotine (0%–6%) from “no nicotine” to “very high nicotine.” Participants also viewed pairs of nicotine concentrations (eg, 18 mg/mL vs. 5%) and indicated which concentration was stronger or if the concentrations were equivalent. Results On average, participants correctly identified 5.92 (2.68) of 18 nicotine strengths, correctly identifying strengths labeled as mg/mL (3.47 [2.03]) more often than percent nicotine (2.45 [1.38], p &lt; .001). Excluding nicotine-free, participants rated concentrations presented as mg/mL as stronger, more addictive, and more harmful than equivalent concentrations presented as percent nicotine. Participants seldom correctly identified that one concentration was stronger or that both were equivalent (7.58 [5.88] of 19 pairings), although they more often correctly identified the stronger concentration when it was presented in mg/mL (4.02 [SD = 3.01]) than in percent nicotine (2.53 [2.73], p &lt; .001). The most consistent predictor of correct answers on these tasks was familiarity with using both products labeled as mg/mL and labeled as percent nicotine. Conclusions Young e-cigarette users had difficulty understanding nicotine concentrations labeled using the most common metrics, raising concerns about inadvertent exposure to high nicotine levels and suggesting that a more intuitive labeling approach is needed. Implications This study extends prior work showing that young e-cigarette users often are uncertain whether the e-liquids they use contain nicotine by demonstrating that adolescents and young adults have difficulty understanding nicotine concentrations labeled using the two most common metrics (mg/mL and percent nicotine). Errors generally underestimated nicotine strength, and users were not able to accurately compare nicotine concentrations presented as mg/mL and percent nicotine. Difficulty understanding labeling metrics persisted even after accounting for user characteristics like age and vaping experience, suggesting that a novel, easy to understand labeling system is needed to convey information about nicotine strength accurately.
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Geste, Jean R., Brandon Levin, Isaac Wilks, et al. "Relationship Between Nicotine Intake and Reward Function in Rats With Intermittent Short Versus Long Access to Nicotine." Nicotine & Tobacco Research 22, no. 2 (2019): 213–23. http://dx.doi.org/10.1093/ntr/ntz052.
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Abstract Introduction Tobacco use improves mood states and smoking cessation leads to anhedonia, which contributes to relapse. Animal studies have shown that noncontingent nicotine administration enhances brain reward function and leads to dependence. However, little is known about the effects of nicotine self-administration on the state of the reward system. Methods To investigate the relationship between nicotine self-administration and reward function, rats were prepared with intracranial self-stimulation electrodes and intravenous catheters. The rats were trained on the intracranial self-stimulation procedure and allowed to self-administer 0.03 mg/kg/infusion of nicotine. All rats self-administered nicotine daily for 10 days (1 hour/day) and were then switched to an intermittent short access (ShA, 1 hour/day) or long access (LgA, 23 hour/day) schedule (2 days/week, 5 weeks). Results During the first 10 daily, 1-hour sessions, nicotine self-administration decreased the reward thresholds, which indicates that nicotine potentiates reward function. After switching to the intermittent LgA or ShA schedule, nicotine intake was lower in the ShA rats than the LgA rats. The LgA rats increased their nicotine intake over time and they gradually consumed a higher percentage of their nicotine during the light phase. The nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine induced a larger increase in reward thresholds (ie, anhedonia) in the LgA rats than the ShA rats. In the LgA rats, nAChR blockade with mecamylamine decreased nicotine intake for 2 hours and this was followed by a rebound increase in nicotine intake. Conclusions A brief period of nicotine self-administration enhances reward function and a high level of nicotine intake leads to dependence. Implications These animal studies indicate that there is a strong relationship between the level of nicotine intake and brain reward function. A high level of nicotine intake was more rewarding than a low level of nicotine intake and nicotine dependence was observed after long, but not short, access to nicotine. This powerful combination of nicotine reward and withdrawal makes it difficult to quit smoking. Blockade of nAChRs temporarily decreased nicotine intake, but this was followed by a large rebound increase in nicotine intake. Therefore, nAChR blockade might not decrease the use of combustible cigarettes or electronic cigarettes.
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Levin, Edward D., Corinne Wells, Susan Slade, et al. "Prolonging the Reduction of Nicotine Self-Administration in Rats by Coadministering Chronic Nicotine With Amitifadine, a Triple Monoamine Reuptake Inhibitor With CYP2B6 Inhibitory Actions." Nicotine & Tobacco Research 22, no. 2 (2019): 232–37. http://dx.doi.org/10.1093/ntr/ntz054.
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Abstract Introduction Existing treatments can aid tobacco smoking cessation, but they have low efficacy. Because there is a network of neural systems involved in tobacco addiction, combination treatments may provide greater efficacy. Chronic nicotine and amitifadine have each been shown to significantly reduce nicotine self-administration in rats. This study was conducted to determine if the combination of chronic nicotine with amitifadine, a triple monoamine reuptake inhibitor with CYP2B inhibitory effects, would reduce nicotine self-administration to a greater extent than either alone or placebo. Methods This study tested the combination of nicotine plus amitifadine in young adult female Sprague-Dawley rats self-administering nicotine (0.03 mg/kg/infusion). This combination was compared with each treatment alone and the vehicle during continuing nicotine self-administration as well as during resumption of self-administration after a week of enforced abstinence, modeling a quit attempt. Finally, we studied the residual effects of these therapies after discontinuation of treatment. Results Treatment with either chronic nicotine or amitifadine alone significantly reduced nicotine self-administration relative to controls. The combination of the treatments significantly enhanced this effect. After treatment withdrawal, all of the groups showed increases in nicotine self-administration, but only the combined treatment group remained significantly below control rates of nicotine self-administration. Conclusions This study showed the promise of amitifadine as a possible new treatment for smoking cessation and suggested that amitifadine is more effective when given with chronic nicotine. The improved efficacy of the amitifadine and nicotine combination may be potentiated by amitifadine’s inhibitory effects on CYP2B, which slows nicotine metabolism. Implications This study replicated the effects that chronic nicotine or chronic amitifadine, a triple reuptake inhibitor, significantly reduces nicotine self-administration in rats. It extends those findings by showing that the combination of chronic nicotine plus amitifadine causes significantly greater reduction in nicotine self-administration than either drug treatment alone. The combination of chronic amitifadine and chronic nicotine also causes a persistent significant reduction in nicotine self-administration after the end of treatment. The amitifadine and nicotine treatment should be assessed in humans to determine whether this combination provides greater efficacy in smoking cessation than transdermal nicotine treatment alone.
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Patel, Minal, Alison F. Cuccia, Yitong Zhou, et al. "Nicotine Perceptions and Response to Proposed Low-Nicotine Cigarette Policy." Tobacco Regulatory Science 5, no. 6 (2019): 480–90. http://dx.doi.org/10.18001/trs.5.6.1.
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Objective: Proposed regulation may establish nicotine standards in cigarettes to sub-addictive levels. In this study, we explore the association between nicotine perceptions and responses to a reduced nicotine policy scenario among current smokers. Methods: Data from a nationally representative sample of 18-54-year-old current tobacco users were collected in March-April 2018 (N = 1746). Current smokers (N = 854) were asked about nicotine-related health beliefs and nicotine addiction. Time to first cigarette (TTFC) was used to examine nicotine dependence. Adjusted and weighted logistic regression models examined these nicotine-related factors in association to support for a proposed government policy and related behavioral intentions. Results: Although 63% of survey participants accurately identified nicotine alone as the addiction cause, 49% incorrectly indicated that cancer and 56% indicated that increased health risk caused by cigarette smoking comes from nicotine. Smokers showed high support (72%) for a proposed low-nicotine policy. Greater misperception about nicotine harm was associated with greater odds (aOR = 1.66, p < .05) of policy support. Shorter TTFC was associated with greater intent to smoke low-nicotine cigarettes but was not associated with policy support. Conclusion: Evidence could inform health message development to address knowledge and misperceptions around nicotine when garnering public support for a low-nicotine policy.
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Kalra, Roma, Shashi P. Singh, Juan C. Pena-Philippides, Raymond J. Langley, Seddigheh Razani-Boroujerdi, and Mohan L. Sopori. "Immunosuppressive and Anti-Inflammatory Effects of Nicotine Administered by Patch in an Animal Model." Clinical Diagnostic Laboratory Immunology 11, no. 3 (2004): 563–68. http://dx.doi.org/10.1128/cdli.11.3.563-568.2004.
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ABSTRACT To study the immunological effects of nicotine, there are several rodent models for chronic nicotine administration. These models include subcutaneously implanted miniosmotic pumps, nicotine-spiked drinking water, and self-administration via jugular cannulae. Administration of nicotine via these routes affects the immune system. Smokers frequently use nicotine patches to quit smoking, and the immunological effects of nicotine patches are largely unknown. To determine whether the nicotine patch affects the immune system, nicotine patches were affixed daily onto the backs of Lewis rats for 3 to 4 weeks. The patches efficiently raised the levels of nicotine and cotinine in serum and strongly inhibited the antibody-forming cell response of spleen cells to sheep red blood cells. The nicotine patch also suppressed the concanavalin A-induced T-cell proliferation and mobilization of intracellular Ca2+ by spleen cells, as well as the fever response of animals to subcutaneous administration of turpentine. Moreover, immunosuppression was associated with chronic activation of protein tyrosine kinase and phospholipase C-γ1 activities. Thus, in this animal model of nicotine administration, the nicotine patch efficiently raises the levels of nicotine and cotinine in serum and impairs both the immune and inflammatory responses.
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McEwen, Andy, Robert West, and Maria Gaiger. "Nicotine Absorption From Seven Current Nicotine Replacement Products and a New Wide-Bore Nicotine Delivery Device." Journal of Smoking Cessation 3, no. 2 (2008): 117–23. http://dx.doi.org/10.1375/jsc.3.2.117.
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AbstractThis preliminary laboratory study investigated nicotine absorption rates of seven current nicotine replacement therapy (NRT) products and a new wide-bore nicotine delivery device (the ‘Nicotine Cannon’). The nicotine products (Cannon, inhalator, nasal spray, microtab, 2 mg and 4 mg gum and 2 mg and 4 mg lozenge) were used for ten minutes by two non-nicotine tolerant subjects. Blood was taken at frequent intervals for the next 60 minutes and plasma nicotine concentrations assessed. Of current NRT products investigated the 4 mg lozenge performed best with the highest blood nicotine levels at each time point, the 2 mg gum delivered the lowest concentrations at each time point. The nicotine nasal spray delivered nicotine the fastest of all the products. The Cannon delivered the highest blood nicotine concentration (mean 8.95 ng/ml) of all products one minute after device use had stopped, and the highest concentration (11 ng/ml) five minutes after termination of use. The Cannon showed it could deliver nicotine relatively rapidly in a manner that was readily tolerated by users.
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Robble, Mykel A., Isaiah L. Holloway, Elysia Ridener, et al. "Differential Effects of Nicotine and Nicotine Withdrawal on Fear Conditioning in Male Rats." International Journal of Neuropsychopharmacology 23, no. 7 (2020): 469–79. http://dx.doi.org/10.1093/ijnp/pyaa024.
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Abstract Background Tobacco use is prevalent in individuals who are routinely exposed to stress. However, little is known about how nicotine affects responses to trauma. We examined in rats how nicotine exposure affects fear conditioning, a procedure often used to study stress-related psychiatric illness. Methods We examined 2 methods of nicotine exposure: self-administration, modeling voluntary use, and experimenter-programmed subcutaneous administration, modeling medicinal administration (nicotine patch). For self-administered nicotine, rats trained to self-administer nicotine i.v. were fear conditioned (via light cue preceding foot-shock) either immediately after a 12-hour self-administration session or 12 hours later during a period with somatic signs of nicotine withdrawal. For experimenter-delivered nicotine, rats were conditioned after 1–21 days of nicotine delivered by programmable (12 hours on) subcutaneous mini-pumps. Tests to evaluate acoustic startle responses to the conditioning environment (context-potentiated startle) and in the presence or absence of the light cue (fear-potentiated startle) occurred after a 10-day period. Results Rats fear conditioned immediately after nicotine self-administration showed reduced responses to the shock-associated context, whereas those trained during nicotine withdrawal showed exaggerated responses. Experimenter-programmed nicotine produced effects qualitatively similar to those seen with self-administered nicotine. Conclusions Self-administration or experimenter-programmed delivery of nicotine immediately before exposure to aversive events can reduce conditioned fear responses. In contrast, exposure to aversive events during nicotine withdrawal exacerbates fear responses. These studies raise the possibility of developing safe and effective methods to deliver nicotine or related drugs to mitigate the effects of stress while also highlighting the importance of preventing withdrawal in nicotine-dependent individuals.
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Villanti, Andrea C., Shelly Naud, Julia C. West, et al. "Latent Classes of Nicotine Beliefs Correlate with Perceived Susceptibility and Severity of Nicotine and Tobacco Products in US Young Adults." Nicotine & Tobacco Research 21, Supplement_1 (2019): S91—S100. http://dx.doi.org/10.1093/ntr/ntz156.
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Abstract Background Pervasive misperceptions about nicotine may influence uptake of quit smoking aids and the impact of policies addressing nicotine as a tobacco product constituent. Methods Latent class analyses were conducted using four items on nicotine beliefs asked of 4037 adults aged 18–40 in wave 9 (February–March 2016) of the Truth Initiative Young Adult Cohort Study. Confirmatory factor analyses identified three factors from 12 items: nicotine susceptibility (NSUS), nicotine severity (NSEV), and tobacco severity (TSEV). Analyses assessed correlations between latent classes, sociodemographics, and nicotine/tobacco factor scores. Results A four-class model of nicotine beliefs was the best fit, with the largest class believing that nicotine plays a major part in smoking risks (class 1, n = 2070; 52%). Class 2 shared that belief but also responded “Don’t know” to addiction questions (class 2, n = 382; 11%). Fewer belonged in class 3, who reported that nicotine plays a small part in health risks (n = 1277; 30%), and class 4, who perceived nicotine as not cancer causing (n = 308; 7%). Latent class membership was correlated with sociodemographics, peer smoking, and past 30-day tobacco use. Classes 1 and 2 had similar NSUS scores and classes 3 and 4 had similar NSEV and TSEV scores. Discussion Differences in the perceptions of nicotine and tobacco-related harms can be partially explained by clustering of underlying nicotine beliefs. These classes of beliefs are correlated with sociodemographic predictors of smoking. These findings may help to identify specific beliefs or groups to be targeted by public education efforts on nicotine. Implications The current study supports that underlying nicotine beliefs are associated with perceived harms of specific nicotine and tobacco products (relative to cigarettes), with greater false beliefs about nicotine correlated with greater perceived susceptibility to nicotine addiction. Two important inferences emerge from this study: first, that education to address nicotine beliefs may also reframe perceptions of the harms of nicotine and tobacco products; and second, that this type of education may differentially impact perceptions of the harms of nicotine products (e.g., nicotine replacement therapy and e-cigarettes) and tobacco products (e.g., cigars, smokeless, and hookah).
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Chellian, Ranjithkumar, Ryann Wilson, Michaela Polmann, Parker Knight, Azin Behnood-Rod, and Adriaan W. Bruijnzeel. "Evaluation of Sex Differences in the Elasticity of Demand for Nicotine and Food in Rats." Nicotine & Tobacco Research 22, no. 6 (2019): 925–34. http://dx.doi.org/10.1093/ntr/ntz171.
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Abstract Introduction Animal studies can inform policy regarding nicotine levels in tobacco products and e-cigarette solutions. Increasing the price of nicotine-containing products decreases their use, but it is unknown how the relationship between price and consumption is affected by both sex and nicotine dose. Methods A behavioral economics procedure was used to determine the demand elasticity for nicotine in male and female rats. Demand elasticity describes the relationship between price and consumption. A high level of elasticity indicates that consumption is relatively sensitive to increases in price. The rats self-administered a low dose (0.01 mg/kg/inf) or a standard dose (0.03 mg/kg/inf) of nicotine for 9 days under a fixed-ratio (FR) 1 schedule. Then the price (FR schedule) of nicotine was increased, and a demand analysis was conducted. A similar study was conducted with palatable food pellets. Results There were no sex differences in nicotine or food intake under the FR1 schedule. However, demand for 0.03 mg/kg/inf of nicotine was more elastic in females than males. Demand for 0.01 mg/kg/inf of nicotine and food was more elastic in males than females. Conclusions These findings indicate that there are no differences in nicotine and food intake between males and females when the price is low. When the price of nicotine or food is increased, males maintain their old level of intake longer than females when they have access to a standard dose of nicotine, and females maintain their intake longer when they have access to a low dose of nicotine or food. Implications This behavioral economics analysis indicates that there is no sex difference in nicotine intake when the price of nicotine is low. Increasing the price of nicotine decreases nicotine intake in a dose- and sex-specific manner. Males maintain their old level of intake longer when they have access to a standard dose of nicotine and females when they have access to a low dose. This has implications for tobacco regulatory policy. In a regulatory environment where only low nicotine-containing products are allowed, increasing the price of nicotine products may lead to a greater decrease in nicotine use in males than females.
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Owari, Miyatake, and Suzuki. "Relationship between Food Dependence and Nicotine Dependence in Smokers: A Cross-Sectional Study of Staff and Students at Medical Colleges." Medicina 55, no. 5 (2019): 202. http://dx.doi.org/10.3390/medicina55050202.
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Background and objectives: The aim of this study was to examine the relationship between nicotine dependence and food dependence in smokers. Smoking and obesity are both serious public health problems that give rise to diseases and increased medical expenses. Nicotine dependence is one of the sources of difficulty in smoking cessation, while food dependence is one of the causes of obesity. Materials and Methods: We examined the data of 72 (smoking vs. nonsmoking) and 62 (nicotine dependence vs. no nicotine dependence) subjects among 321 staff and students at medical colleges in Kagawa and Okayama prefectures in Japan. Results: There was a significant difference in food dependence (except women) between the smoking and nonsmoking groups (total: smoking 4.7 ± 6.1, nonsmoking 2.1 ± 2.0, p = 0.0411; men: smoking 4.0 ± 4.7, nonsmoking 2.0 ± 2.1, p = 0.0490). There was also a significant difference in food dependence (except women) between the nicotine dependence and no nicotine dependence groups (total: nicotine dependence 4.6 ± 6.3, no nicotine dependence 2.0 ± 2.1, p = 0.0370; men: nicotine dependence 3.6 ± 4.8, no nicotine dependence 1.6 ± 1.8, p = 0.0489). Conclusion: The findings showed that the smoking group (and nicotine dependence group) had higher food dependence than the nonsmoking group (and no nicotine dependence group). Our results indicate an interdependence between nicotine and food dependences.
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Dambrauskiene, K., V. Adomaitiene, J. Klumbiene, J. Petkeviciene, and A. Veryga. "The Fagerström Test for Nicotine Dependence in Lithuanian Adult Smokers." European Psychiatry 24, S1 (2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70642-x.
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Nicotine dependence meets the criteria for a psychiatric diagnosis, and has been referred to as “the most prevalent, most deadly, most costly, yet most treatable of all psychiatric disorders”. Fagerström test for nicotine dependence is an instrument often used to assess nicotine dependence. In the last decade, the importance of the level of nicotine dependence and difficulties in cessation has been acknowledged. Therefore it is important to know the level of nicotine dependence for choosing nicotine replacement as a function of dose.Objective:The aim of the study was to evaluate nicotine dependence among Lithuanian adult smokers, according to gender, age, and former quit attempts.Methods:The study analyses data of Lithuanian adult population health behavior surveys, performed in period of 1994- 2006. For every survey the national random sample of 3000 inhabitants aged 20-64 was taken from the National Population Register. The study material was collected through mailed questionnaires covering smoking habits. Nicotine dependence was assessed with Fagerström test for nicotine dependence (FTND).Results:Among Lithuanian regular smokers aged 20-64 in both genders dominated low level of nicotine dependence (56, 9 % of smokers). High level of nicotine dependence was observed in 2, 4 % of smokers. The men presented higher dependence on nicotine than women. Older smokers presented higher dependence on nicotine than young smokers.
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Bhanu Prakash G, Rajagopalan Vijayaraghavan, Senthilkumar Sivanesan, and Madhankumar Swaminathan. "A study on the agents that reduces the nicotine induced nicotinic receptor density in wistar rats." International Journal of Research in Pharmaceutical Sciences 12, no. 1 (2021): 430–35. http://dx.doi.org/10.26452/ijrps.v12i1.4074.
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The most important substance causing addiction towards cigarette is nicotine. Nicotine abstinence causes withdrawal symptoms in smokers. It is not just nicotine, along with it is the upregulation of nicotinic receptor density (NRD) that leads to addiction. All together makes nicotine deaddiction the most difficult aspect. Nicotine receptor density increases as long as the person is exposed to nicotine. When once the NRD is initiated by nicotine, later though you stop smoking, the increased nicotine receptors create an urge to smoke. Hence the person feels to smoke for satisfying the nicotine receptors. The smokers may attempt to quit smoking but the NRD will create an urge for nicotine again. One cannot completely quit smoking or cannot stop taking nicotine, until the NRD is reduced to normal. In our present study we have studied the effect of citric acid and tyrosine on decreasing nicotinic receptor density. We have induced the nicotinic receptor density to raise and studied the citric acid and tyrosine’s effect in maintaining the NRD closer to normal. The study concludes that citric acid and tyrosine have reduced the NRD significantly. This can control withdrawal symptoms and can stop craving for nicotine and finally can lead to cessation of smoking and from taking nicotine therapy.
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Mihasan, Marius, Calin-Bogdan Chiribau, Thorsten Friedrich, Vlad Artenie, and Roderich Brandsch. "An NAD(P)H-Nicotine Blue Oxidoreductase Is Part of the Nicotine Regulon and May Protect Arthrobacter nicotinovorans from Oxidative Stress during Nicotine Catabolism." Applied and Environmental Microbiology 73, no. 8 (2007): 2479–85. http://dx.doi.org/10.1128/aem.02668-06.
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ABSTRACT An NAD(P)H-nicotine blue (quinone) oxidoreductase was discovered as a member of the nicotine catabolic pathway of Arthrobacter nicotinovorans. Transcriptional analysis and electromobility shift assays showed that the enzyme gene was expressed in a nicotine-dependent manner under the control of the transcriptional activator PmfR and thus was part of the nicotine regulon of A. nicotinovorans. The flavin mononucleotide-containing enzyme uses NADH and, with lower efficiency, NADPH to reduce, by a two-electron transfer, nicotine blue to the nicotine blue leuco form (hydroquinone). Besides nicotine blue, several other quinones were reduced by the enzyme. The NAD(P)H-nicotine blue oxidoreductase may prevent intracellular one-electron reductions of nicotine blue which may lead to semiquinone radicals and potentially toxic reactive oxygen species.
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Dukes, Angeline J., James P. Fowler, Valeria Lallai, Anna N. Pushkin, and Christie D. Fowler. "Adolescent Cannabinoid and Nicotine Exposure Differentially Alters Adult Nicotine Self-Administration in Males and Females." Nicotine & Tobacco Research 22, no. 8 (2020): 1364–73. http://dx.doi.org/10.1093/ntr/ntaa084.
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Abstract Introduction During adolescence, exposure to nicotine or cannabis independently induces effects on neuromaturation and later cognitive function. However, the potential effect of both drugs under co-use conditions has become of increasing concern given the prevalence of e-cigarettes, legalization of cannabis, and availability of synthetic “spice” cannabinoid agonists. Aims and Methods The current studies investigated the effects of exposure to a cannabinoid receptor agonist (WIN55,212-2) and/or nicotine over a discrete time period in mid-adolescence on later intravenous nicotine self-administration in adult male and female mice. We further examined whether cannabinoid agonist administration in adulthood would alter nicotine reinforcement, with either acute or chronic pairing across 7 days. Results We found that adult males exhibited increased nicotine self-administration at a lower, rewarding nicotine dose following adolescent cannabinoid exposure, either alone or with nicotine coadministration. In contrast, adult females demonstrated an opposing effect in which adolescent cannabinoid and nicotine coexposure resulted in decreased nicotine intake compared with the nicotine only and control groups. Furthermore, after maintaining nicotine self-administration across sessions, pretreatment with a low dose of the cannabinoid agonist decreased nicotine intake in both male and female control mice, and this lowering effect was evidenced after both acute and chronic treatment. However, the cannabinoid agonist was ineffective in altering nicotine intake in mice previously exposed to nicotine, cannabinoid agonist, or both during adolescence. Conclusions These data provide evidence that adolescent drug exposure can alter later nicotine reinforcement in a sex-specific manner and can further modulate the effectiveness of interventions in reducing nicotine intake during adulthood. Implications These studies demonstrate a significant impact of nicotine, cannabinoids, or coexposure on developmental processes during adolescence. Differential effects were observed within each sex, with opposing results found for cannabinoid exposure on nicotine intake in males and females. Intriguingly, we also evidenced resistance to the lowering effects of a cannabinoid agonist on nicotine intake in adulthood based on adolescent drug exposure. Thus, these findings have important implications for our understanding of the impact of nicotine and cannabinoids (eg, Δ9-tetrahydrocannabinol (THC) and synthetic “spice” cannabinoids) during development, with further implications for the effectiveness of therapeutic interventions based on prior drug exposure in youth.
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Kallupi, Marsida, Song Xue, Bin Zhou, Kim D. Janda, and Olivier George. "An enzymatic approach reverses nicotine dependence, decreases compulsive-like intake, and prevents relapse." Science Advances 4, no. 10 (2018): eaat4751. http://dx.doi.org/10.1126/sciadv.aat4751.
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Tobacco use disorder is the leading cause of disease and preventable death worldwide, but current medications that are based on pharmacodynamics have low efficacy. Novel pharmacokinetic approaches to prevent nicotine from reaching the brain have been tested using vaccines, but these efforts have failed because antibody affinity and concentration are not sufficient to completely prevent nicotine from reaching the brain. We provide preclinical evidence of the efficacy of an enzymatic approach to reverse nicotine dependence, reduce compulsive-like nicotine intake, and prevent relapse in rats with a history of nicotine dependence. Chronic administration of NicA2-J1, an engineered nicotine-degrading enzyme that was originally isolated from Pseudomonas putida S16, completely prevented nicotine from reaching the brain and reversed somatic signs of withdrawal, hyperalgesia, and irritability-like behavior in nicotine-dependent rats with a history of escalation of nicotine self-administration. NicA2-J1 also decreased compulsive-like nicotine intake, reflected by responding despite the adverse consequences of contingent footshocks, and prevented nicotine- and stress (yohimbine)–induced relapse. These results demonstrate the efficacy of enzymatic therapy in treating nicotine addiction in advanced animal models and provide a strong foundation for the development of biological therapies for smoking cessation in humans.
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Feng, Min, Nathan L. Sparkman, Nan Sui, and Ming Li. "A drug–drug conditioning paradigm reveals multiple antipsychotic–nicotine interactions." Journal of Psychopharmacology 31, no. 4 (2016): 474–86. http://dx.doi.org/10.1177/0269881116681471.
Full textAbstract:
Clinical studies indicate a reciprocal impact between nicotine use and antipsychotic medications in patients with schizophrenia. The present study used a conditioned avoidance response (CAR) test (a behavioral test of antipsychotic effect) and examined the specific drug–drug interactions between nicotine and haloperidol or clozapine. Following acquisition of the avoidance response, rats were first tested under either vehicle, nicotine (0.2, 0.4 mg/kg, sc), haloperidol (0.025, 0.05 mg/kg, sc), clozapine (5.0, 10.0 mg/kg, sc), or a combination of nicotine and haloperidol or nicotine and clozapine for seven consecutive days. Afterward, they were challenged with nicotine (0.2 mg/kg), haloperidol (0.025 mg/kg), or clozapine (5.0 mg/kg) in the CAR to assess if haloperidol or clozapine affected the behavioral effect of nicotine on avoidance response and if nicotine altered the avoidance suppressive effect of haloperidol and clozapine. During the seven avoidance drug test days, nicotine did not alter the avoidance suppressive effect of haloperidol or clozapine. However, in the challenge test, prior nicotine treatment (0.2 mg/kg) attenuated haloperidol’s (0.05 mg/kg) sensitized effect on avoidance response. On the other hand, prior haloperidol treatment increased nicotine’s (0.2 mg/kg) avoidance disruptive effect, and even engendered nicotine 0.4 mg/kg to exhibit an “acquired” avoidance suppressive effect. The combined nicotine and clozapine treatment did not produce any detectable interactive effects on avoidance response and motor activity. These findings suggest that nicotine is capable of altering the long-term antipsychotic efficacy of haloperidol, while haloperidol can alter the behavioral effects of nicotine. Clozapine and nicotine are less likely to influence each other.