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1.
J Chem Phys ; 141(22): 224114, 2014 Dec 14.
Article in English | MEDLINE | ID: mdl-25494739

ABSTRACT

In this work, we report a comparative study of computed excitation energies, oscillator strengths, and excited-state energy gradients of (S)-nicotine, chosen as a test case, using multireference methods, coupled cluster singles and doubles, and methods based on time-dependent density functional theory. This system was chosen because its apparent simplicity hides a complex electronic structure, as several different types of valence excitations are possible, including n-π(*), π-π(*), and charge-transfer states, and in order to simulate its spectrum it is necessary to describe all of them consistently well by the chosen method.


Subject(s)
Ganglionic Stimulants/chemistry , Nicotine/chemistry , Electrons , Gases/chemistry , Models, Molecular , Quantum Theory
2.
Exp Dermatol ; 22(8): 524-9, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23802681

ABSTRACT

Stress is an important condition of modern life. Nicotine addiction can modulate the physiological response to stress. Cutaneous healing is a complex process resulting in scar formation, which can be delayed by stress. Therefore, the aim of this study was to investigate the effects of nicotine administration on cutaneous wound healing in chronically stressed mice. Male mice were submitted to rotational stress, whereas control animals were not subjected to stress. These stressed and control animals were treated with a transdermal nicotine patch that was changed every day. A full-thickness excisional lesion was also generated, and 14 days later, lesions had recovered. However, the Stress + Nicotine group presented a delay in wound contraction. These wounds showed a decrease in inflammatory cell infiltration and lower expression of transforming growth factor-ß (TGF-ß), whereas there was an increase in angiogenesis and tumor necrosis factor-α (TNF-α) expression. In vitro fibroblast migration was also impaired by the nicotine treatment of stressed-stimulated cells. In conclusion, nicotine administration potentiates the delay in wound closure observed in mice submitted to stress.


Subject(s)
Nicotine/administration & dosage , Nicotine/chemistry , Stress, Physiological , Wound Healing/drug effects , Administration, Cutaneous , Animals , Cell Differentiation , Cell Movement , Cell Proliferation , Fibroblasts/cytology , Fibroblasts/drug effects , Ganglionic Stimulants/administration & dosage , Ganglionic Stimulants/chemistry , Inflammation , Male , Mice , Neovascularization, Pathologic , Time Factors , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor-alpha/metabolism
3.
AAPS PharmSciTech ; 12(1): 21-7, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21161460

ABSTRACT

Bilayer nicotine mucoadhesive patches were prepared and evaluated to determine the feasibility of the formulation as a nicotine replacement product to aid in smoking cessation. Nicotine patches were prepared using xanthan gum or carbopol 934 as a mucoadhesive polymers and ethyl cellulose as a backing layer. The patches were evaluated for their thickness, weight and content uniformity, swelling behavior, drug-polymers interaction, adhesive properties, and drug release. The physicochemical interactions between nicotine and the polymers were investigated by Fourier transform infrared (FTIR) spectroscopy. Mucoadhesion was assessed using two-arm balance method, and the in vitro release was studied using the Franz cell. FTIR revealed that there was an acid base interaction between nicotine and carbopol as well as nicotine and xanthan. Interestingly, the mucoadhesion and in vitro release studies indicated that this interaction was strong between the drug and carbopol whereas it was weak between the drug and xanthan. Loading nicotine concentration to non-medicated patches showed a significant decrease in the mucoadhesion strength of carbopol patches and no significant effect on the mucoadhesion strength of xanthan patches. In vitro release studies of the xanthan patches showed a reasonable fast initial release profile followed by controlled drug release over a 10-h period.


Subject(s)
Acrylates/chemistry , Excipients/chemistry , Ganglionic Stimulants/chemistry , Nicotine/administration & dosage , Polysaccharides, Bacterial/chemistry , Smoking Cessation , Adhesiveness , Adhesives , Administration, Buccal , Chemistry, Pharmaceutical , Delayed-Action Preparations , Drug Stability , Ganglionic Stimulants/administration & dosage , In Vitro Techniques , Nicotine/chemistry
4.
Annu Rev Pharmacol Toxicol ; 49: 57-71, 2009.
Article in English | MEDLINE | ID: mdl-18834313

ABSTRACT

Nicotine sustains tobacco addiction, a major cause of disability and premature death. Nicotine binds to nicotinic cholinergic receptors, facilitating neurotransmitter release and thereby mediating the complex actions of nicotine in tobacco users. Dopamine, glutamate, and gamma aminobutyric acid release are particularly important in the development of nicotine dependence, and corticotropin-releasing factor appears to contribute to nicotine withdrawal. Nicotine dependence is highly heritable. Genetic studies indicate roles for nicotinic receptor subtypes, as well as genes involved in neuroplasticity and learning, in development of dependence. Nicotine is primarily metabolized by CYP 2A6, and variability in rate of metabolism contributes to vulnerability to tobacco dependence, response to smoking cessation treatment, and lung cancer risk. Tobacco addiction is much more common in persons with mental illness and substance abuse disorders, representing a high proportion of current smokers. Pharmacotherapeutic approaches to tobacco addiction include nicotine replacement, bupropion, and varenicline, the latter a selective nicotine receptor partial agonist.


Subject(s)
Behavior, Addictive/chemically induced , Behavior, Addictive/drug therapy , Ganglionic Stimulants/toxicity , Nicotine/toxicity , Nicotinic Agonists/toxicity , Smoking/adverse effects , Tobacco Use Disorder/drug therapy , Tobacco Use Disorder/etiology , Animals , Behavior, Addictive/genetics , Benzazepines/therapeutic use , Bupropion/therapeutic use , Ganglionic Stimulants/chemistry , Ganglionic Stimulants/metabolism , Ganglionic Stimulants/pharmacokinetics , Humans , Nicotine/chemistry , Nicotine/metabolism , Nicotine/pharmacokinetics , Nicotinic Agonists/chemistry , Nicotinic Agonists/metabolism , Nicotinic Agonists/pharmacokinetics , Nonprescription Drugs/therapeutic use , Quinoxalines/therapeutic use , Varenicline
5.
Nicotine Tob Res ; 10(11): 1645-52, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18988077

ABSTRACT

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


Subject(s)
Carcinogens/analysis , Ganglionic Stimulants/analysis , Nicotine/analysis , Nitrosamines/analysis , Smoke/analysis , Tobacco, Smokeless/chemistry , Centers for Disease Control and Prevention, U.S. , Chromatography, Liquid , Ganglionic Stimulants/chemistry , Humans , Hydrogen-Ion Concentration , Nicotine/chemistry , Reference Values , United States , Water/analysis
6.
Environ Sci Technol ; 39(6): 1479-91, 2005 Mar 15.
Article in English | MEDLINE | ID: mdl-15819200

ABSTRACT

Little is known about the molecular composition of the biodegradable fraction of dissolved organic matter (BDOM) in stream ecosystems. We combined plug-flow biofilm reactors, tetramethylammonium hydroxide (TMAH) thermochemolysis GC-MS, and 13C-labeled TMAH thermochemolysis GC-MS to study the molecular composition of BDOM from two stream ecosystems. TMAH products derived from fatty acids, lignin, and other aromatic molecules were quantified using an internal standard approach. We applied the 13C-TMAH thermochemolysis procedure to differentiate between compounds in dissolved organic matter (DOM) that had natural methoxyl groups from those that acquired methoxyl groups during the TMAH reaction. In Rio Tempisquito, a stream draining a tropical evergreen forest, and White Clay Creek, a stream draining a temperate deciduous woodlands, carbohydrates, fatty acids, and lignin contributed to the DOM and BDOM molecular composition. We observed 97 different peaks in the chromatograms of streamwater, with 57% of the peaks common to both streams. The DOM and BDOM pools from each site also contained a unique suite of compounds. Our combined use of TMAH and 13C-TMAH thermochemolysis revealed that heterotrophic bacteria can selectively degrade and demethylate different types of compounds in the lignin residues of DOM. This demonstration of bacterial demethylation of lignin, an abundant and refractory plant molecule, has potential implications for global carbon cycling.


Subject(s)
Biofilms , Bioreactors , Carbon/metabolism , Ganglionic Stimulants/chemistry , Quaternary Ammonium Compounds/chemistry , Biodegradation, Environmental , Gas Chromatography-Mass Spectrometry , Organic Chemicals/metabolism , Temperature
7.
Nicotine Tob Res ; 5(6): 885-9, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14668072

ABSTRACT

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.


Subject(s)
Ganglionic Stimulants/analysis , Nicotine/analysis , Tobacco, Smokeless/chemistry , Biological Availability , Centers for Disease Control and Prevention, U.S. , Ganglionic Stimulants/chemistry , Ganglionic Stimulants/pharmacokinetics , Humans , Hydrogen-Ion Concentration , Nicotine/chemistry , Nicotine/pharmacokinetics , Reference Values , Tobacco Industry , United States , Water/analysis
8.
J Anal Toxicol ; 25(7): 607-11, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11599608

ABSTRACT

To explore drug-melanin interactions, we examined the in vitro tyrosinase-mediated formation of melanin from tyrosine in the presence of the 3H-cocaine (3H-COC), 3H-flunitrazepam (3H-FLU), and 3H-nicotine (3H-NIC) at 10-100,000 ng/mL. Polymerization in the presence of 10 or 100 ng/mL of each drug resulted in almost complete drug incorporation into the melanin pellet. Only 12% (3H-NIC) to 28% (3H-FLU) of the pellet-associated radioactivity could be released upon treatment with 6 M HCl. At 1000-100,000 ng/mL, between 20 and 50% of label became melanin-associated. In each case a significant percentage of melanin-associated radioactivity was resistant to treatment with 6 M HCl. Nicotine-associated radioactivity in the polymer was subject to much greater quenching than was 3H-COC or 3H-FLU, suggesting a much tighter association with the melanin. The subsequent demonstration of a covalent adduct of a melanin intermediate and nicotine has demonstrated the utility of this polymerization system as a model for further chemical characterization of drug-melanin interactions.


Subject(s)
Cocaine/pharmacokinetics , Flunitrazepam/pharmacokinetics , GABA Modulators/pharmacokinetics , Ganglionic Stimulants/pharmacokinetics , Melanins/chemistry , Narcotics/pharmacokinetics , Nicotine/pharmacokinetics , Tritium , Cocaine/chemistry , Drug Interactions , Flunitrazepam/chemistry , GABA Modulators/chemistry , Ganglionic Stimulants/chemistry , Hair/chemistry , Humans , Narcotics/chemistry , Nicotine/chemistry , Polymers , Tritium/pharmacokinetics
9.
Environ Sci Technol ; 35(3): 560-7, 2001 Feb 01.
Article in English | MEDLINE | ID: mdl-11351729

ABSTRACT

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


Subject(s)
Air Pollution, Indoor/analysis , Ganglionic Stimulants/chemistry , Manufactured Materials , Nicotine/chemistry , Phenanthrenes/chemistry , Adsorption , Ganglionic Stimulants/analysis , Humans , Kinetics , Nicotine/analysis , Organic Chemicals , Phenanthrenes/analysis , Smoking , Volatilization
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