Effect of ginseng saponina on nicotine-induced dopamine release in the rat nucleus accumbens and striatum

Energy Technology Data Exchange (ETDEWEB)

Kim, Sang Eun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Shim, In Sop [Kyunghee University, Seoul (Korea, Republic of); Chung, June Key; Lee, Myung Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2002-10-01

We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum and nucleus accumbens of freely moving rats using in vivo microdialysis technique. Systemic pretreatment with GTS decreased striatal DA release induced by local infusion of nicotine into the striatum. However, GTS had no effect on the resting levels of extracellular DA in the striatum. GTS also blocked nicotine-induced DA release in the nucleus accumbens. The results of the present study suggest that GTS acts on the DA terminals to prevent DA release induced by nicotine. This may reflect the blocking effect of GTS on behavioral hyperactivity induced by psychostimulants.

On the solubility of nicotinic acid and isonicotinic acid in water and organic solvents

International Nuclear Information System (INIS)

Abraham, Michael H.; Acree, William E.

2013-01-01

Highlights: ► Solubilities of nicotinic acid and isonicotinic acids in organicsolvents have been determined. ► Solubilities are used to calculate Abraham descriptors for the two acids. ► These descriptors then yield water-solvent and gas-solvent partitions into numerous solvents. ► The solubility of the neutral acids in water is obtained. ► The method is straightforward and can be applied to any set of compound solubilities. -- Abstract: We have determined the solubility of nicotinic acid in four solvents and the solubility of isonicotinic acid in another four solvents. These results, together with literature data on the solubility of nicotinic acid in five other organic solvents and isonicotinic acid in four other organic solvents, have been analyzed through two linear Gibbs energy relationships in order to extract compound properties, or descriptors, that encode various solute–solvent interactions. The descriptors for nicotinic acid and isonicotinic acid can then be used in known equations for partition of solutes between water and organic solvents to predict partition coefficients and then further solubility in a host of organic solvents, as well as to predict a number of other physicochemical properties

Synthesis of non-aggregated nicotinic acid coated magnetite nanorods via hydrothermal technique

Energy Technology Data Exchange (ETDEWEB)

Attallah, Olivia A., E-mail: olivia.adly@hu.edu.eg [Center of Nanotechnology, Nile University, 12677 Giza (Egypt); Pharmaceutical Chemistry Department, Heliopolis University, 11777 El Salam, Cairo (Egypt); Girgis, E. [Solid State Physics Department, National Research Center, 12622 Dokki, Giza (Egypt); Advanced Materials and Nanotechnology Lab, CEAS, National Research Center, 12622 Dokki, Giza (Egypt); Abdel-Mottaleb, Mohamed M.S.A. [Center of Nanotechnology, Nile University, 12677 Giza (Egypt)

2016-02-01

Non-aggregated magnetite nanorods with average diameters of 20–30 nm and lengths of up to 350 nm were synthesized via in situ, template free hydrothermal technique. These nanorods capped with different concentrations (1, 1.5, 2 and 2.5 g) of nicotinic acid (vitamin B3); possessed good magnetic properties and easy dispersion in aqueous solutions. Our new synthesis technique maintained the uniform shape of the nanorods even with increasing the coating material concentration. The effect of nicotinic acid on the shape, particle size, chemical structure and magnetic properties of the prepared nanorods was evaluated using different characterization methods. The length of nanorods increased from 270 nm to 350 nm in nicotinic acid coated nanorods. Goethite and magnetite phases with different ratios were the dominant phases in the coated samples while a pure magnetite phase was observed in the uncoated one. Nicotinic acid coated magnetic nanorods showed a significant decrease in saturation magnetization than uncoated samples (55 emu/g) reaching 4 emu/g in 2.5 g nicotinic acid coated sample. The novel synthesis technique proved its potentiality to prepare coated metal oxides with one dimensional nanostructure which can function effectively in different biological applications. - Highlights: • We synthesize nicotinic acid coated magnetite nanorods via hydrothermal technique • Effect of nicotinic acid concentration on the nanorods properties was significant • Nanorods maintained uniform shape with increased concentration of nicotinic acid • Alterations occurred in particle size, mineral phases and magnetics of coated samples.

Synthesis of non-aggregated nicotinic acid coated magnetite nanorods via hydrothermal technique

International Nuclear Information System (INIS)

Attallah, Olivia A.; Girgis, E.; Abdel-Mottaleb, Mohamed M.S.A.

2016-01-01

Non-aggregated magnetite nanorods with average diameters of 20–30 nm and lengths of up to 350 nm were synthesized via in situ, template free hydrothermal technique. These nanorods capped with different concentrations (1, 1.5, 2 and 2.5 g) of nicotinic acid (vitamin B3); possessed good magnetic properties and easy dispersion in aqueous solutions. Our new synthesis technique maintained the uniform shape of the nanorods even with increasing the coating material concentration. The effect of nicotinic acid on the shape, particle size, chemical structure and magnetic properties of the prepared nanorods was evaluated using different characterization methods. The length of nanorods increased from 270 nm to 350 nm in nicotinic acid coated nanorods. Goethite and magnetite phases with different ratios were the dominant phases in the coated samples while a pure magnetite phase was observed in the uncoated one. Nicotinic acid coated magnetic nanorods showed a significant decrease in saturation magnetization than uncoated samples (55 emu/g) reaching 4 emu/g in 2.5 g nicotinic acid coated sample. The novel synthesis technique proved its potentiality to prepare coated metal oxides with one dimensional nanostructure which can function effectively in different biological applications. - Highlights: • We synthesize nicotinic acid coated magnetite nanorods via hydrothermal technique • Effect of nicotinic acid concentration on the nanorods properties was significant • Nanorods maintained uniform shape with increased concentration of nicotinic acid • Alterations occurred in particle size, mineral phases and magnetics of coated samples.

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

Inhibiting Effect of Nicotinic Acid Hydrazide on Corrosion of Aluminum and Mild Steel in Acidic Medium

Energy Technology Data Exchange (ETDEWEB)

Bhat, J. Ishwara [Mangalore Univ., Karnataka (India); Alva, Vijaya D. P. [Shree Devi Institute of Technology, Karnataka (India)

2014-02-15

The corrosion behavior of aluminum and mild steel in hydrochloric acid medium was studied using a nicotinic acid hydrazide as inhibitor by potentiodynamic polarization, electrochemical impedance spectroscopy technique and gravimetric methods. The effects of inhibitor concentration and temperature were investigated. The experimental results suggested, nicotinic acid hydrazide is a good corrosion inhibitor for both aluminum and mild steel in hydrochloric acid medium and the inhibition efficiency increased with increase in the inhibitor concentration. The polarization studies revealed that nicotinic acid hydrazide exhibits mixed type of inhibition. The inhibition was assumed to occur via adsorption of the inhibitor molecules on the aluminum and mild steel surface and inhibits corrosion by blocking the reaction sites on the surface of aluminum.

Inhibiting Effect of Nicotinic Acid Hydrazide on Corrosion of Aluminum and Mild Steel in Acidic Medium

International Nuclear Information System (INIS)

Bhat, J. Ishwara; Alva, Vijaya D. P.

2014-01-01

The corrosion behavior of aluminum and mild steel in hydrochloric acid medium was studied using a nicotinic acid hydrazide as inhibitor by potentiodynamic polarization, electrochemical impedance spectroscopy technique and gravimetric methods. The effects of inhibitor concentration and temperature were investigated. The experimental results suggested, nicotinic acid hydrazide is a good corrosion inhibitor for both aluminum and mild steel in hydrochloric acid medium and the inhibition efficiency increased with increase in the inhibitor concentration. The polarization studies revealed that nicotinic acid hydrazide exhibits mixed type of inhibition. The inhibition was assumed to occur via adsorption of the inhibitor molecules on the aluminum and mild steel surface and inhibits corrosion by blocking the reaction sites on the surface of aluminum

Studies on the riboflavin, pantothenic acid, nicotinic acid and choline requirements of young Embden geese

Science.gov (United States)

Serafin, J.A.

1981-01-01

Four experiments were conducted to examine the riboflavin, pantothenic acid, nicotinic acid, and choline requirements of young Embden geese fed purified diets. Goslings fed diets deficient in either riboflavin, pantothenic acid, nicotinic acid, or choline grew poorly. Feeding a pantothenic acid-deficient diet resulted in 100% mortality. Goslings fed diets containing 530 mg/kg of choline or less developed perosis. Under the conditions of these experiments it was found that: 1) goslings require no more than 3.84 mg/kg of riboflavin and 31.2 mg/kg of nicotinic acid in the diet for rapid growth and normal development, 2) the pantothenic acid requirement of goslings is no more than 12.6 mg/kg of diet, and 3) a dietary choline level of 1530 mg/kg is adequate for both the prevention of perosis and rapid growth of goslings. The levels of vitamins found to support normal growth and development of goslings appear to be similar to requirements of other species that have been examined.

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

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

Science.gov (United States)

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

2017-05-31

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

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

Science.gov (United States)

Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J

2016-05-01

Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

Nicotinic acid as a new co-adsorbent in dye-sensitized solar cells

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Phuong Tuyet, E-mail: ntphuong@hcmus.edu.vn [Faculty of Chemistry, University of Science, Vietnam National University, Ho Chi Minh City (Viet Nam); Nguyen, Vinh Son; Phan, Thu Anh Pham; Le, Tan Nhut Van; Le, Duyen My; Le, Duy Dang; Tran, Vy Anh [Faculty of Chemistry, University of Science, Vietnam National University, Ho Chi Minh City (Viet Nam); Huynh, Tuan Van [Faculty of Physics and Engineering Physics, University of Science, Vietnam National University, Ho Chi Minh City (Viet Nam); Lund, Torben [Department of Science, Systems and Models, Roskilde University DK-4000 (Denmark)

2017-01-15

Highlights: • Adsorption of Nicotinic acid on TiO{sub 2} surface is characterized by IR and XPS analysis. • The blocking effect of Nicotinic acid toward electron transfer on TiO{sub 2} electrode is indicated by recent developed method of cyclic voltammetry. • Low concentration of Nicotinic acid (<10 mM) helps to increase the amount of dye loading on TiO{sub 2} surface. • The use of Nicotinic acid at optimum concentration improves the efficiency of the resulting DSC from 3.14 to 5.02%. • Nicotinic acid enhances the cell performance by the same extend as other standard co-adsorbents at optimum concentrations. - Abstract: With the aim of introduction a new inexpensive co-adsorbent to improve solar cell performance, the influence of nicotinic acid (NTA) used as a co-adsorbent in dye-sensitized solar cells (DSCs) was investigated. The findings showed that low concentrations of NTA (<10 mM) increased the N719 ruthenium dye loading on the TiO{sub 2} electrode surface by 10–12%, whereas higher concentrations of NTA lowered the dye loading. The adsorption of NTA onto the TiO{sub 2} electrode surface was studied by attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, and the blocking effect of NTA toward electron transfer between the electrode and 1,4-dicyanonaphthalene (redox couple electrolyte probe) was investigated by cyclic voltammetry. Subsequently, the performance of NTA in functional DSCs was evaluated by current–voltage (J–V) DSC characterization and compared with that of DSCs fabricated with two well-established co-adsorbents i.e., chenodeoxycholic acid (CDA) and octadecylphosphonic acid (OPA). The findings showed that under optimized co-adsorbent concentration (1 mM NTA, 0.03 mM CDA, 0.015 mM OPA), the efficiency of the corresponding solar cells increased to the same extent. Specifically, the use of NTA at optimum concentration improved the efficiency of the resulting DSC from 3.14 to 5.02%.

Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

Science.gov (United States)

Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

2008-01-01

The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

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.

Expression patterns of nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase in human malignant lymphomas

DEFF Research Database (Denmark)

Olesen, Uffe Høgh; Hastrup, Nina; Sehested, Maxwell

2011-01-01

The purpose of the study was to determine in human malignant lymphomas the expression patterns of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT), the primary, rate-limiting enzymes in the synthesis of NAD+. NAMPT is a potential biomarker...... for sensitivity to NAMPT inhibitors and NAPRT is a biomarker for the use of nicotinic acid as a chemoprotectant in treatment with NAMPT inhibitors. The NAMPT inhibitor, APO866, is currently in clinical phase II trials in lymphomas. The expression of NAMPT and NAPRT was investigated in 53 samples of malignant.......0024). In conclusion, FL are a promising target for NAMPT inhibitors whereas substantial subsets of malignant lymphomas especially in Hodgkin lymphoma may be suitable for a combination treatment with nicotinic acid and NAMPT inhibitors....

The Kinetics and Mechanism for the Oxidation of Nicotinic Acid by Peroxomonosulfate in Acidic Aqueous Medium

Energy Technology Data Exchange (ETDEWEB)

Agrawal, Anju; Sailani, Riya; Gupta, Beena; Khandelwal, C. L.; Sharma, P. D. [Univ. of Rajasthan, Jaipur (India)

2012-04-15

The kinetics of oxidation of nicotinic acid by peroxomonosulfate (PMS) has been studied in acetate buffers. Stoichiometry of the reaction corresponds to the reaction of one mole of the oxidant with a mole of nicotinic acid. N→O product has been confirmed both by UV visible and IR spectroscopy. The reaction is second order viz. first order with respect to each reactant. Activation parameters have also been evaluated. A plausible reaction mechanism is mentioned and the derived kinetic rate law accounts for experimental observations.

The Kinetics and Mechanism for the Oxidation of Nicotinic Acid by Peroxomonosulfate in Acidic Aqueous Medium

International Nuclear Information System (INIS)

Agrawal, Anju; Sailani, Riya; Gupta, Beena; Khandelwal, C. L.; Sharma, P. D.

2012-01-01

The kinetics of oxidation of nicotinic acid by peroxomonosulfate (PMS) has been studied in acetate buffers. Stoichiometry of the reaction corresponds to the reaction of one mole of the oxidant with a mole of nicotinic acid. N→O product has been confirmed both by UV visible and IR spectroscopy. The reaction is second order viz. first order with respect to each reactant. Activation parameters have also been evaluated. A plausible reaction mechanism is mentioned and the derived kinetic rate law accounts for experimental observations

Nicotinic acid as a nontoxic corrosion inhibitor for hot dipped Zn and Zn-Al alloy coatings on steels in diluted hydrochloric acid

Energy Technology Data Exchange (ETDEWEB)

Ju Hong [Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071 (China); Graduate School, Chinese Academy of Sciences, Beijing 100039 (China); Li Yan [Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071 (China)], E-mail: yanlee@ms.qdio.ac.cn

2007-11-15

The inhibition effect of nicotinic acid for corrosion of hot dipped Zn and Zn-Al alloy coatings in diluted hydrochloric acid was investigated using quantum chemistry analysis, weight loss test, electrochemical measurement, and scanning electronic microscope (SEM) analysis. Quantum chemistry calculation results showed that nicotinic acid possessed planar structure with a number of active centers, and the populations of the Mulliken charge, the highest occupied molecular orbital (HOMO), and the lowest unoccupied molecular orbital (LUMO) were found mainly focused around oxygen and nitrogen atoms, and the cyclic of the benzene as well. The results of weight loss test and electrochemical measurement indicated that inhibition efficiency (IE%) increased with inhibitor concentration, and the highest inhibition efficiency was up to 96.7%. The corrosion inhibition of these coatings was discussed in terms of blocking the electrode reaction by adsorption of the molecules at the active centers on the electrode surface. It was found that the adsorption of nicotinic acid on coating surface followed Langmuir adsorption isotherm with single molecular layer, and nicotinic acid adsorbed on the coating surface probably by chemisorption. Nicotinic acid, therefore, can act as a good nontoxic corrosion inhibitor for hot dipped Zn and Zn-Al alloy coatings in diluted hydrochloric acid solution.

Attenuating Nicotine Reinforcement and Relapse by Enhancing Endogenous Brain Levels of Kynurenic Acid in Rats and Squirrel Monkeys.

Science.gov (United States)

Secci, Maria E; Auber, Alessia; Panlilio, Leigh V; Redhi, Godfrey H; Thorndike, Eric B; Schindler, Charles W; Schwarcz, Robert; Goldberg, Steven R; Justinova, Zuzana

2017-07-01

The currently available antismoking medications have limited efficacy and often fail to prevent relapse. Thus, there is a pressing need for newer, more effective treatment strategies. Recently, we demonstrated that enhancing endogenous levels of kynurenic acid (KYNA, a neuroinhibitory product of tryptophan metabolism) counteracts the rewarding effects of cannabinoids by acting as a negative allosteric modulator of α7 nicotinic receptors (α7nAChRs). As the effects of KYNA on cannabinoid reward involve nicotinic receptors, in the present study we used rat and squirrel monkey models of reward and relapse to examine the possibility that enhancing KYNA can counteract the effects of nicotine. To assess specificity, we also examined models of cocaine reward and relapse in monkeys. KYNA levels were enhanced by administering the kynurenine 3-monooxygenase (KMO) inhibitor, Ro 61-8048. Treatment with Ro 61-8048 decreased nicotine self-administration in rats and monkeys, but did not affect cocaine self-administration. In rats, Ro 61-8048 reduced the ability of nicotine to induce dopamine release in the nucleus accumbens shell, a brain area believed to underlie nicotine reward. Perhaps most importantly, Ro 61-8048 prevented relapse-like behavior when abstinent rats or monkeys were reexposed to nicotine and/or cues that had previously been associated with nicotine. Ro 61-8048 was also effective in monkey models of cocaine relapse. All of these effects of Ro 61-8048 in monkeys, but not in rats, were reversed by pretreatment with a positive allosteric modulator of α7nAChRs. These findings suggest that KMO inhibition may be a promising new approach for the treatment of nicotine addiction.

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

International Nuclear Information System (INIS)

Kuwahara, Masaaki

1978-01-01

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

Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A

International Nuclear Information System (INIS)

Tang, Yuting; Zhou, Lubing; Gunnet, Joseph W.; Wines, Pamela G.; Cryan, Ellen V.; Demarest, Keith T.

2006-01-01

HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. The molecular mechanisms whereby niacin exerts its pleiotropic effects on lipid metabolism remain largely unknown. In addition, the most common side effect in niacin therapy is skin flushing that is caused by prostaglandin release, suggesting that the phospholipase A 2 (PLA 2 )/arachidonic acid (AA) pathway is involved. Various eicosanoids have been shown to activate peroxisome-proliferator activated receptors (PPAR) that play a diverse array of roles in lipid metabolism. To further elucidate the potential roles of HM74A in mediating the therapeutic effects and/or side effects of niacin, we sought to explore the signaling events upon HM74A activation. Here we demonstrated that HM74A synergistically enhanced UTP- and bradykinin-mediated AA release in a pertussis toxin-sensitive manner in A431 cells. Activation of HM74A also led to Ca 2+ -mobilization and enhanced bradykinin-promoted Ca 2+ -mobilization through Gi protein. While HM74A increased ERK1/2 activation by the bradykinin receptor, it had no effects on UTP-promoted ERK1/2 activation.Furthermore, UTP- and bradykinin-mediated AA release was significantly decreased in the presence of both MAPK kinase inhibitor PD 098059 and PKC inhibitor GF 109203X. However, the synergistic effects of HM74A were not dramatically affected by co-treatment with both inhibitors, indicating the cross-talk occurred at the receptor level. Finally, stimulation of A431 cells transiently transfected with PPRE-luciferase with AA significantly induced luciferase activity, mimicking the effects of PPARγ agonist rosiglitazone, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs

Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A

Energy Technology Data Exchange (ETDEWEB)

Tang, Yuting [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Zhou, Lubing [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Gunnet, Joseph W [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Wines, Pamela G [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Cryan, Ellen V [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States); Demarest, Keith T [Endocrine Therapeutics and Metabolic Disorders, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Rt. 202, Raritan, NJ 08869 (United States)

2006-06-23

HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. The molecular mechanisms whereby niacin exerts its pleiotropic effects on lipid metabolism remain largely unknown. In addition, the most common side effect in niacin therapy is skin flushing that is caused by prostaglandin release, suggesting that the phospholipase A{sub 2} (PLA{sub 2})/arachidonic acid (AA) pathway is involved. Various eicosanoids have been shown to activate peroxisome-proliferator activated receptors (PPAR) that play a diverse array of roles in lipid metabolism. To further elucidate the potential roles of HM74A in mediating the therapeutic effects and/or side effects of niacin, we sought to explore the signaling events upon HM74A activation. Here we demonstrated that HM74A synergistically enhanced UTP- and bradykinin-mediated AA release in a pertussis toxin-sensitive manner in A431 cells. Activation of HM74A also led to Ca{sup 2+}-mobilization and enhanced bradykinin-promoted Ca{sup 2+}-mobilization through Gi protein. While HM74A increased ERK1/2 activation by the bradykinin receptor, it had no effects on UTP-promoted ERK1/2 activation.Furthermore, UTP- and bradykinin-mediated AA release was significantly decreased in the presence of both MAPK kinase inhibitor PD 098059 and PKC inhibitor GF 109203X. However, the synergistic effects of HM74A were not dramatically affected by co-treatment with both inhibitors, indicating the cross-talk occurred at the receptor level. Finally, stimulation of A431 cells transiently transfected with PPRE-luciferase with AA significantly induced luciferase activity, mimicking the effects of PPAR{gamma} agonist rosiglitazone, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs.

Copper Complexes of Nicotinic-Aromatic Carboxylic Acids as Superoxide Dismutase Mimetics

Directory of Open Access Journals (Sweden)

Virapong Prachayasittikul

2008-12-01

Full Text Available Nicotinic acid (also known as vitamin B3 is a dietary element essential for physiological and antihyperlipidemic functions. This study reports the synthesis of novel mixed ligand complexes of copper with nicotinic and other select carboxylic acids (phthalic, salicylic and anthranilic acids. The tested copper complexes exhibited superoxide dismutase (SOD mimetic activity and antimicrobial activity against Bacillus subtilis ATCC 6633, with a minimum inhibition concentration of 256 μg/mL. Copper complex of nicotinic-phthalic acids (CuNA/Ph was the most potent with a SOD mimetic activity of IC50 34.42 μM. The SOD activities were observed to correlate well with the theoretical parameters as calculated using density functional theory (DFT at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complex CuNA/Ph was positively correlated with the electron affinity (EA value. The two quantum chemical parameters, highest occupied molecular orbital (HOMO and lowest unoccupied molecular orbital (LUMO, were shown to be appropriate for understanding the mechanism of the metal complexes as their calculated energies show good correlation with the SOD activity. Moreover, copper complex with the highest SOD activity were shown to possess the lowest HOMO energy. These findings demonstrate a great potential for the development of value-added metallovitamin-based therapeutics.

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.

Comparison of efficacy of the phosphate binders nicotinic acid and sevelamer hydrochloride in hemodialysis patients

Directory of Open Access Journals (Sweden)

Farrokhlagha Ahmadi

2012-01-01

Full Text Available Hyperphosphatemia is a significant risk factor for the development of ectopic calcification and coronary artery diseases in patients on hemodialysis (HD, and must be controlled with the use of phosphate binders. Studies comparing the effects of sevelamer and nicotinic acid, both similar non-calcium and non-aluminum phosphate binders, are not available. In this study, 40 patients on HD with a serum phosphorus level of more than 6 mg/dL were enrolled. After a two week washout period without phosphate binders, the patients were randomly divided into two equal groups (n = 20 and were started on nicotinic acid or sevelamer for a period of four weeks. The dose of nicotinic acid used was 500 mg and that of sevelamer was 1600 mg daily. Blood samples were drawn for the measurement of the total calcium (Ca, phosphorus (P, alkaline phosphatase (ALP, triglyceride (TG, total cholesterol (Chol, high-density lipoprotein (HDL, low-density lipoprotein (LDL, uric acid and parathyroid hormone (PTH. Patients receiving sevelamer showed a significant reduction in serum P level (2.2 ± 0.69 mg/dL; P <0.0001 in comparison with the nicotinic acid group (1.7 ± 1.06 mg/dL; P = 0.004. Reduction in the Ca-P product was significantly different in the two groups; in the sevelamer group, it was 21 ± 7; (P <0.0001 while in the nicotinic acid group, it was 16 ± 11 (P = 0.007. Also, patients on sevelamer showed greater reduction in the mean TG level (38.9 ± 92 mg/dL; P = 0.005. No significant changes were observed in the mean serum Ca, total Chol, HDL, LDL, ALP and iPTH levels in the two study groups. Our short-term study suggests that although nicotinic acid reduced hyperphosphatemia, sevelamer showed higher efficacy in controlling hyperphosphatemia as well as the Ca-P product.

[Effects of excess nicotinic acid on growth and the urinary excretion of B-group vitamins and the metabolism of tryptophan in weaning rats].

Science.gov (United States)

Fukuwatari, Tsutomu; Kurata, Kaori; Shibata, Katsumi

2009-04-01

To determine the tolerable upper intake level of nicotinic acid in humans, we investigated the effects of excess nicotinic acid administration on body weight gain, food intake, and urinary excretion of water-soluble vitamins and the metabolism of tryptophan in weaning rats. The weaning rats were freely fed a niacin-free 20% casein diet (control diet) or the same diet with 0.1%, 0.3% or 0.5% nicotinic acid for 23 days. The excess nicotinic acid intake did not affect body weight gain, food intake, serotonin contents in the brain, stomach and small intestine, or the urinary excretions of water-soluble vitamins. Although excess nicotinic acid did not affect the upper part of the tryptophan-nicotinamide pathway, 0.5% nicotinic acid diet increased the urinary excretion of quinolinic acid. The diet containing more than 0.3% nicotinic acid also increased the urinary excretion of nicotinic acid, which is usually below the limit of detection. As determined from the results of body weight gain and food intake as indices for apparent adverse effects, the no-observed-adverse-effect-level (NOAEL) for nicotinic acid was 0.5% in diet, corresponding to 450 mg/kg body weight/day. As judged from in increase of urinary quinolinic acid and nicotinic acid as indices of metabolic change, NOAEL was 0.1% in diet, corresponding to 90 mg/kg body weight/day, and the lowest-observed-adverse-effect-level (LOAEL) was 0.3% in diet, corresponding to 270 mg/kg body weight/day.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

The role of adrenal hormones in the activation of tryptophan 2,3-dioxygenase by nicotinic acid in rat liver.

Science.gov (United States)

Sainio, E L

1997-09-01

In this study, our previous finding that nicotinic acid activates tryptophan 2,3-dioxygenase as strongly as tryptophan was investigated in further detail. This study focused on the role of the adrenals in the activation process. Adrenalectomy abolished the activation due to nicotinic acid, but not the activation caused by tryptophan. The role of corticoids and/or adrenomedullary hormones in the enzyme activation was studied, by supplementing these hormones in adrenalectomized rats using minipumps implanted under the skin. The results showed that the enhanced activity of tryptophan 2,3-dioxygenase caused by nicotinic acid was partly restored by adrenaline following adrenalectomy but not by corticosterone supplementation. The results were supported by further experiments in which the rats were treated with adrenaline or corticosterone intraperitoneally before nicotinic acid administration. The conclusion that adrenaline participates in the regulation of tryptophan 2,3-dioxygenase should promote further study to determine whether adrenaline is a general modulator of this enzyme. This experimental model generated new information on the activation mechanism of tryptophan 2,3-dioxygenase by nicotinic acid.

Protective efficacy of folic acid and vitamin B12 against nicotine-induced toxicity in pancreatic islets of the rat

Directory of Open Access Journals (Sweden)

Bhattacharjee Ankita

2015-06-01

Full Text Available Although cigarette smoking is associated with insulin resistance and an increased risk for type 2 diabetes, few studies have examined the effect of nicotine on the adult endocrine pancreas. In this study, male Wister rats were treated with nicotine (3 mg/kg body weight/day with or without supplementation of folic acid (36 μg/kg body weight/day or vitamin B12 (0.63 μg/kg body weight/day alone or in combination. Fasting blood glucose, insulin and HBA1C level and different oxidative and anti-oxidative stress parameters were measured and pancreatic tissue sections were stained with eosin-haematoxylene. Data were analysed by nonparametric statistics. The results revealed that nicotine induced prediabetes condition with subsequent damage to pancreatic islets in rats. Nicotine also caused oxidative stress in pancreatic tissue as evidenced by increased nitric oxide and malondialdehyde level and decreased superoxide dismutase, catalase and reduced glutathione level. Compared to vitamin B12 supplementation, folic acid blunted the nicotine-induced toxicity in pancreatic islets with higher efficacy. Further, folic acid and vitamin B12 in combination were able to confer significant protection on pancreatic islets against nicotine induced toxicity. These results suggest that supplementation of folic acid and vitamin B12 in combination may be a possible strategy of detoxification against nicotine-induced toxicity in pancreatic islets of the rat.

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.

Coefficients of interphase distribution and Gibbs energy of the transfer of nicotinic acid from water into aqueous solutions of ethanol and dimethylsulfoxide

Science.gov (United States)

Grazhdan, K. V.; Gamov, G. A.; Dushina, S. V.; Sharnin, V. A.

2012-11-01

Coefficients of the interphase distribution of nicotinic acid are determined in aqueous solution systems of ethanol-hexane and DMSO-hexane at 25.0 ± 0.1°C. They are used to calculate the Gibbs energy of the transfer of nicotinic acid from water into aqueous solutions of ethanol and dimethylsulfoxide. The Gibbs energy values for the transfer of the molecular and zwitterionic forms of nicotinic acid are obtained by means of UV spectroscopy. The diametrically opposite effect of the composition of binary solvents on the transfer of the molecular and zwitterionic forms of nicotinic acid is noted.

Endogenous opioids inhibit oxytocin release during nicotine-stimulated secretion of vasopressin in man.

Science.gov (United States)

Seckl, J R; Johnson, M; Shakespear, C; Lightman, S L

1988-05-01

The effects of the opioid antagonist naloxone on the vasopressin (AVP) and oxytocin (OT) responses to nicotine were studied in male non-smokers (21-30 years old). Either saline (n = 6) or naloxone (4 mg bolus + 6 mg/h, n = 6) was infused i.v. during the study. After 60 min infusion the subjects smoked one high-nicotine content cigarette. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Smoking led to a significant rise in plasma vasopressin in both saline and naloxone-infused subjects (P less than 0.05). There was no significant difference in the plasma AVP response to smoking between the two groups. Saline-infused subjects did not show any change in plasma OT in response to smoking. Naloxone infusion was associated with a significant rise in OT from 1.3 +/- 0.1 pmol/l to 4.3 +/- 2.4 pmol/l 5 min after smoking (P less than 0.05). We conclude that there is endogenous opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to nicotine in man.

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.

alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex.

Science.gov (United States)

Livingstone, Phil D; Srinivasan, Jayaraman; Kew, James N C; Dawson, Lee A; Gotti, Cecilia; Moretti, Milena; Shoaib, Mohammed; Wonnacott, Susan

2009-02-01

Nicotine enhances attentional and working memory aspects of executive function in the prefrontal cortex (PFC) where dopamine plays a major role. Here, we have determined the nicotinic acetylcholine receptor (nAChR) subtypes that can modulate dopamine release in rat PFC using subtype-selective drugs. Nicotine and 5-Iodo-A-85380 (beta2* selective) elicited [(3)H]dopamine release from both PFC and striatal prisms in vitro and dopamine overflow from medial PFC in vivo. Blockade by dihydro-beta-erythroidine supports the participation of beta2* nAChRs. However, insensitivity of nicotine-evoked [(3)H]dopamine release to alpha-conotoxin-MII in PFC prisms suggests no involvement of alpha6beta2* nAChRs, in contrast to the striatum, and this distinction is supported by immunoprecipitation of nAChR subunits from these tissues. The alpha7 nAChR-selective agonists choline and Compound A also promoted dopamine release from PFC in vitro and in vivo, and their effects were enhanced by the alpha7 nAChR-selective allosteric potentiator PNU-120596 and blocked by specific antagonists. DNQX and MK801 inhibited [(3)H]dopamine release evoked by choline and PNU-120596, suggesting crosstalk between alpha7 nAChRs, glutamate and dopamine in the PFC. In vivo, systemic (but not local) administration of PNU-120596, in the absence of agonist, facilitated dopamine overflow in the medial PFC, consistent with the activation of extracortical alpha7 nAChRs by endogenous acetylcholine or choline. These data establish that both beta2* and alpha7 nAChRs can modulate dopamine release in the PFC in vitro and in vivo. Through their distinct actions on dopamine release, these nAChR subtypes could contribute to executive function, making them specific therapeutic targets for conditions such as schizophrenia and attention deficit hyperactivity disorder.

Determination and confirmation of nicotinic acid and its analogues and derivates in pear and apple blossoms using high-performance liquid chromatography-diode array-electrospray ionization mass spectrometry.

Science.gov (United States)

Paternoster, Thomas; Vrhovsek, Urska; Pertot, Ilaria; Duffy, Brion; Gessler, Cesare; Mattivi, Fulvio

2009-11-11

Erwinia amylovora causes fire blight, a serious disease of apple and pear. The bacterial pathogen colonizes the flower stigma and hypanthium, where it multiplies and then invades through natural openings (nectarthodes). E. amylovora requires nicotinic acid as growth factor, and competition for nicotinic acid is being explored as a novel biocontrol strategy. The ability of E. amylovora to substitute nicotinic acid with analogues or derivates as growth factors has not been investigated yet. Furthermore, the presence and/or variable concentration of nicotinic acid and its analogues/derivates in the hypanthium could be associated with the different susceptibilities to fire blight of hosts and nonhosts and with the differential sensitivity to the disease among apple and pear varieties. Currently, no methods to specifically quantify nicotinic acid and nicotinic acid analogues/derivates in the hypanthium of apple and pear blossoms are available. This study demonstrates that E. amylovora can grow using nicotinamide and 6-hydroxynicotinic acid as alternative growth factors to nicotinic acid, but not using 2-hydroxynicotinic acid. A novel HPLC/ES-MS method was developed for the detection and quantification of nicotinic acid and its analogues/derivates directly in the hypanthium of apple and pear blossoms. Analyses established the presence of nicotinic acid and nicotinamide, whereas no detectable amounts of 6-hydroxynicotinic acid and 2-hydroxynicotinic acid were observed. Mean nicotinic acid content in the pear hypanthium was found to be approximately 2 orders of magnitude higher than in the apple hypanthium, which may contribute to the differential susceptibility of these two host species to fire blight. Contents of nicotinamide were in contrast similar. Nicotinic acid can therefore be considered a relevant factor in the pathogen establishment in pear blossoms, whereas nicotinamide could cover a primary role in apple blossoms.

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

Science.gov (United States)

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

2008-12-17

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

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.

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.

Positron emission tomography (PET) imaging of nicotine-induced dopamine release in squirrel monkeys using [18F]Fallypride.

Science.gov (United States)

Naylor, Jennifer E; Hiranita, Takato; Matazel, Katelin S; Zhang, Xuan; Paule, Merle G; Goodwin, Amy K

2017-10-01

Nicotine, the principal psychoactive tobacco constituent, is thought to produce its reinforcing effects via actions within the mesolimbic dopamine (DA) system. The objective of the current study was to examine the effect of nicotine on DA D 2 /D 3 receptor availability in the nonhuman primate brain with the use of the radioligand [ 18 F]fallypride and positron emission tomography (PET). Ten adult male squirrel monkeys were used in the current study. Each subject underwent two PET scans, one with an injection (IV) of saline and subsequently one with an injection of nicotine (0.032mg/kg). The DA D 2 /D 3 antagonist, [ 18 F]fallypride, was delivered IV at the beginning of each scan, and nicotine or saline was delivered at 45min into the scan. Regions of interest (ROI) were drawn on specific brain regions and these were used to quantify standard uptake values (SUVs). The SUV is defined as the average concentration of radioactivity in the ROI x body weight/injected dose. Using the cerebellum as a reference region, SUV ratios (SUV ROI /SUV cerebellum ) were calculated to compare saline and nicotine effects in each ROI. Two-way repeated ANOVA revealed a significant decrease of SUV ratios in both striatal and extrastriatal regions following an injection of nicotine during the PET scans. Like other drugs of abuse, these results indicate that nicotine administration may produce DA release, as suggested by the decrease in [ 18 F]fallypride signal in striatal regions. These findings from a nonhuman primate model provide further evidence that the mesolimbic DA system is affected by the use of products that contain nicotine. Published by Elsevier B.V.

In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil

Directory of Open Access Journals (Sweden)

André Luís Morais Ruela

2013-09-01

Full Text Available The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC. The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems.

Expression patterns of nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase in human malignant lymphomas.

Science.gov (United States)

Olesen, Uffe Høgh; Hastrup, Nina; Sehested, Maxwell

2011-04-01

The purpose of the study was to determine in human malignant lymphomas the expression patterns of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT), the primary, rate-limiting enzymes in the synthesis of NAD+. NAMPT is a potential biomarker for sensitivity to NAMPT inhibitors and NAPRT is a biomarker for the use of nicotinic acid as a chemoprotectant in treatment with NAMPT inhibitors. The NAMPT inhibitor, APO866, is currently in clinical phase II trials in lymphomas. The expression of NAMPT and NAPRT was investigated in 53 samples of malignant lymphomas (diffuse large B-cell lymphoma, follicular B-cell lymphoma, Hodgkin's lymphoma and peripheral T-cell lymphoma). The expression of NAMPT was generally high in the more aggressive malignant lymphomas, with >80% strong expression, whereas the expression in the more indolent follicular lymphoma (FL) was significantly lower (>75% moderate or low expression, p = 0.0002). NAMPT was very highly expressed in Hodgkin Reed-Sternberg cells in Hodgkin's lymphoma. NAPRT expression was more varied (p > 0.0001) with 30-50% low expression except for Hodgkin's lymphoma where 85% displayed low expression (p = 0.0024). In conclusion, FL are a promising target for NAMPT inhibitors whereas substantial subsets of malignant lymphomas especially in Hodgkin lymphoma may be suitable for a combination treatment with nicotinic acid and NAMPT inhibitors. © 2011 The Authors. APMIS © 2011 APMIS.

Nicotinic acid as a new co-adsorbent in dye-sensitized solar cells

DEFF Research Database (Denmark)

Nguyen, Phuong Tuyet; Nguyen, Vinh Son; Pham Phan, Thu Anh

2017-01-01

With the aim of introduction a new inexpensive co-adsorbent to improve solar cell performance, the influence of nicotinic acid (NTA) used as a co-adsorbent in dye-sensitized solar cells (DSCs) was investigated. The findings showed that low concentrations of NTA (

The NAD+ precursor nicotinic acid improves genomic integrity in human peripheral blood mononuclear cells after X-irradiation.

Science.gov (United States)

Weidele, Kathrin; Beneke, Sascha; Bürkle, Alexander

2017-04-01

NAD + is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD + consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD + levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule. In the present study, we investigated the impact of supplementation with nicotinic acid on resting and proliferating human mononuclear blood cells with a focus on DNA damage and repair processes. We observed that nicotinic acid supplementation increased NAD + levels as well as DNA repair efficiency and enhanced genomic stability evaluated by micronucleus test after x-ray treatment. Interestingly, resting cells displayed lower basal levels of DNA breaks compared to proliferating cells, but break-induction rates were identical. Despite similar levels of p53 protein upregulation after irradiation, higher NAD + concentrations led to reduced acetylation of this protein, suggesting enhanced SIRT1 activity. Our data reveal that even in normal primary human cells cellular NAD + levels may be limiting under conditions of genotoxic stress and that boosting the NAD + system with nicotinic acid can improve genomic stability. Copyright © 2017 Elsevier B.V. All rights reserved.

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...

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

Science.gov (United States)

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

2014-11-01

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

Beta amyloid differently modulate nicotinic and muscarinic receptor subtypes which regulate in vitro and in vivo the release of glycine in the rat hippocampus

Directory of Open Access Journals (Sweden)

Stefania eZappettini

2012-07-01

Full Text Available Using both in vitro (hippocampal synaptosomes in superfusion and in vivo (microdialysis approaches we investigated whether and to what extent β amyloid peptide 1-40 (Aβ 1-40 interferes with the cholinergic modulation of the release of glycine (GLY in the rat hippocampus. The nicotine-evoked overflow of endogenous GLY in hippocampal synaptosomes in superfusion was significantly inhibited by Aβ 1-40 (10 nM while increasing the concentration to 100 nM the inhibitory effect did not further increase. Both the Choline (Ch (α7 agonist; 1 mM and the 5-Iodo-A-85380 dihydrochloride (5IA85380, α4β2 agonist; 10 nM-evoked GLY overflow were inhibited by Aβ1-40 at 100 nM but not at 10nM concentrations. The KCl evoked [3H]GLY and [3H]Acetylcholine (ACh overflow were strongly inhibited in presence of oxotremorine; however this inhibitory muscarinic effect was not affected by Aβ1-40. The effects of Aβ1-40 on the administration of nicotine, veratridine, 5IA85380 and PHA 543613 hydrochloride (PHA543613 (a selective agonist of α7 subtypes on hippocampal endogenous GLY release in vivo were also studied. Aβ 1-40 significantly reduced (at 10 μM but not at 1 μM the nicotine evoked in vivo release of GLY. Aβ 1-40 (at 10 μM but not at 1 μM significantly inhibited the PHA543613 (1 mM-elicited GLY overflow while was ineffective on the GLY overflow evoked by 5IA85380 (1 mM. Aβ 40-1 (10 μM did not produce any inhibitory effect on nicotine evoked GLY overflow both in the in vitro and in vivo experiments. Our results indicate that a the cholinergic modulation of the release of GLY occurs by the activation of both α7 and α4β2 nicotinic ACh receptors (nAChRs as well as by the activation of inhibitory muscarinic ACh receptors (mAChRs and b Aβ 1-40 can modulate cholinergic evoked GLY release exclusively through the interaction with α7 and the α4β2 nAChR nicotinic receptors but not through mAChR subtypes.

The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat

DEFF Research Database (Denmark)

Munro, G; Hansen, Rikke Rie; Erichsen, Hk

2012-01-01

BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators. Increasin......BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators...

Study of thermodynamic and acoustic behaviour of nicotinic acid in binary aqueous mixtures of D-lactose

Science.gov (United States)

Sharma, Ravi; Thakur, R. C.

2017-07-01

In the present study, the thermodynamic properties such as partial molar volumes, partial molar expansibilities, partial molar compressibilities, partial molar heat capacities and isobaric thermal expansion coefficient of different solutions of nicotinic acid in binary aqueous mixtures of D-lactose have been determined at different temperatures (298.15, 303.15, 308.15, 313.15) K. Masson's equation is used to interpret the data in terms of solute-solute and solute-solvent interactions. In the present study it has been found that nicotinic acid behaves as structure maker in aqueous and binary aqueous mixtures of D-lactose.

Nicotinic Acid-Mediated Activation of Both Membrane and Nuclear Receptors towards Therapeutic Glucocorticoid Mimetics for Treating Multiple Sclerosis

Directory of Open Access Journals (Sweden)

W. Todd Penberthy

2009-01-01

Full Text Available Acute attacks of multiple sclerosis (MS are most commonly treated with glucocorticoids, which can provide life-saving albeit only temporary symptomatic relief. The mechanism of action (MOA is now known to involve induction of indoleamine 2,3-dioxygenase (IDO and interleukin-10 (IL-10, where IL-10 requires subsequent heme oxygenase-1 (HMOX-1 induction. Ectopic expression studies reveal that even small changes in expression of IDO, HMOX-1, or mitochondrial superoxide dismutase (SOD2 can prevent demyelination in experimental autoimmune encephalomyelitis (EAE animal models of MS. An alternative to glucocorticoids is needed for a long-term treatment of MS. A distinctly short list of endogenous activators of both membrane G-protein-coupled receptors and nuclear peroxisome proliferating antigen receptors (PPARs demonstrably ameliorate EAE pathogenesis by MOAs resembling that of glucocorticoids. These dual activators and potential MS therapeutics include endocannabinoids and the prostaglandin 15-deoxy-Δ12,14-PGJ2. Nicotinamide profoundly ameliorates and prevents autoimmune-mediated demyelination in EAE via maintaining levels of nicotinamide adenine dinucleotide (NAD, without activating PPAR nor any G-protein-coupled receptor. By comparison, nicotinic acid provides even greater levels of NAD than nicotinamide in many tissues, while additionally activating the PPAR-dependent pathway already shown to provide relief in animal models of MS after activation of GPR109a/HM74a. Thus nicotinic acid is uniquely suited for providing therapeutic relief in MS. However nicotinic acid is unexamined in MS research. Nicotinic acid penetrates the blood brain barrier, cures pellagric dementia, has been used for over 50 years clinically without toxicity, and raises HDL concentrations to a greater degree than any pharmaceutical, thus providing unparalleled benefits against lipodystrophy. Summary analysis reveals that the expected therapeutic benefits of high-dose nicotinic

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.

Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice

NARCIS (Netherlands)

Hanson, Julien; Gille, Andreas; Zwykiel, Sabrina; Lukasova, Martina; Clausen, Björn E.; Ahmed, Kashan; Tunaru, Sorin; Wirth, Angela; Offermanns, Stefan

2010-01-01

The antidyslipidemic drug nicotinic acid and the antipsoriatic drug monomethyl fumarate induce cutaneous flushing through activation of G protein-coupled receptor 109A (GPR109A). Flushing is a troublesome side effect of nicotinic acid, but may be a direct reflection of the wanted effects of

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

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.

Amidase-catalyzed production of nicotinic acid in batch and continuous stirred membrane reactors

Czech Academy of Sciences Publication Activity Database

Cantarella, M.; Cantarella, L.; Gallifuoco, A.; Intellini, R.; Kaplan, Ondřej; Spera, A.; Martínková, Ludmila

2008-01-01

Roč. 42, č. 3 (2008), s. 222-229 ISSN 0141-0229 R&D Projects: GA MŠk OC D25.002 Institutional research plan: CEZ:AV0Z50200510 Keywords : amidase * nicotinic acid bioproduction * temperature dependence Subject RIV: EE - Microbiology, Virology Impact factor: 2.375, year: 2008

Add-on-Statin Extended Release Nicotinic Acid/Laropiprant but Not the Switch to High-Dose Rosuvastatin Lowers Blood Pressure: An Open-Label Randomized Study

Directory of Open Access Journals (Sweden)

Anastazia Kei

2011-01-01

Full Text Available Introduction. Nicotinic acid (NA and statins have been associated with reductions in blood pressure (BP. Patients and Methods. We recruited 68 normotensive and hypertensive dyslipidemic patients who were treated with a conventional statin dose and had not achieved lipid targets. Patients were randomized to switch to high-dose rosuvastatin (40 mg/day or to add-on current statin treatment with extended release (ER NA/laropiprant (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks for 3 months. Results. Switching to rosuvastatin 40 mg/day was not associated with significant BP alterations. In contrast, the addition of ER-NA/laropiprant to current statin treatment resulted in a 7% reduction of systolic BP (from 134±12 to 125±10 mmHg, <.001 versus baseline and =.01 versus rosuvastatin group and a 5% reduction of diastolic BP (from 81±9 to 77±6 mmHg, =.009 versus baseline and =.01 versus rosuvastatin group. These reductions were significant only in the subgroup of hypertensives and were independent of the hypolipidemic effects of ER-NA/laropiprant. Conclusions. Contrary to the switch to high-dose rosuvastatin, the addition of ER-NA/laropiprant to statin treatment was associated with significant reductions in both systolic and diastolic BP.

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....

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

Science.gov (United States)

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

2008-10-15

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

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

Science.gov (United States)

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

2018-03-12

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

Electrochemiluminescence properties of Tb(III) nicotinic acid complex and its analytical application

Energy Technology Data Exchange (ETDEWEB)

Yang, Yu [College of Chemistry and Material Science, Anhui Normal University, No. 1 Beijing East Road, Wuhu 241000 (China); Zhang, Yuqin [The Department of Material Engineering, Wuhu Institute of Technology, No. 201 Wenjin Road, Wuhu 241003 (China); Shu, Guibo; Dong, Qin; Zou, Lili [College of Chemistry and Material Science, Anhui Normal University, No. 1 Beijing East Road, Wuhu 241000 (China); Zhu, Yinggui, E-mail: ygzhu08@mail.ahnu.edu.cn [College of Chemistry and Material Science, Anhui Normal University, No. 1 Beijing East Road, Wuhu 241000 (China)

2015-03-15

A water soluble lanthanide Tb(III) complex Tb{sub 2}(C{sub 6}NO{sub 2}H{sub 4}){sub 6}(H{sub 2}O){sub 4} has been synthesized as luminescent material, and it is characterized by X-ray crystallography, infrared spectra and elemental analysis, respectively. This material showed excellent characterize of electrochemiluminescence (ECL) in the presence of co-reactant potassium peroxodisulfate (K{sub 2}S{sub 2}O{sub 8}) at glassy carbon electrode. With the increase of the concentration for nicotinic acid (NA), the ECL intensity of the complex/K{sub 2}S{sub 2}O{sub 8} system in HAc–NaAc buffer solution will be decreased apparently. Novel approach for the detection of nicotinic acid (NA) was developed based on the quenching effect of NA. Furthermore, the possible mechanisms for the ECL behavior of Tb{sub 2}(C{sub 6}NO{sub 2}H{sub 4}){sub 6}(H{sub 2}O){sub 4}/K{sub 2}S{sub 2}O{sub 8} system are proposed. The effects of K{sub 2}S{sub 2}O{sub 8} concentration, pH of the buffer on the ECL intensity have also been discussed in detail. The experiment results showed that the limit of detection for NA was 6.0×10{sup −7} M (S/N=3) with a linear range of 2.0×10{sup −6}–2.0×10{sup −4} M. - Highlights: • A novel ECL material Tb{sub 2}(H{sub 2}O){sub 4}(C{sub 6}NO{sub 2}H{sub 4}){sub 6} was synthesized and characterized. • The ECL property of the terbium chelate has been studied detail, and possible mechanism was been proposed. • A new ECL method for the determination of nicotinic acid with a wide liner range and a low detection limit was proposed.

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

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.

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

Science.gov (United States)

Osanai, Makoto; Lee, Gang-Hong

2011-06-01

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

The glucagon-like peptide 1 analogue Exendin-4 attenuates the nicotine-induced locomotor stimulation, accumbal dopamine release, conditioned place preference as well as the expression of locomotor sensitization in mice.

Directory of Open Access Journals (Sweden)

Emil Egecioglu

Full Text Available The gastrointestinal peptide glucagon-like peptide 1 (GLP-1 is known to regulate consummatory behavior and is released in response to nutrient ingestion. Analogues of this peptide recently emerged as novel pharmacotherapies for treatment of type II diabetes since they reduce gastric emptying, glucagon secretion as well as enhance glucose-dependent insulin secretion. The findings that GLP-1 targets reward related areas including mesolimbic dopamine areas indicate that the physiological role of GLP-1 extends beyond food intake and glucose homeostasis control to include reward regulation. The present series of experiments was therefore designed to investigate the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4, on established nicotine-induced effects on the mesolimbic dopamine system in mice. Specifically, we show that treatment with Ex4, at a dose with no effect per se, attenuate nicotine-induced locomotor stimulation, accumbal dopamine release as well as the expression of conditioned place preference in mice. In accordance, Ex4 also blocks nicotine-induced expression of locomotor sensitization in mice. Given that development of nicotine addiction largely depends on the effects of nicotine on the mesolimbic dopamine system these findings indicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for nicotine cessations in humans.

Uptake of [14C]nicotinic acid and [14C]nicotinamide by Bordetella pertussis

International Nuclear Information System (INIS)

McPheat, W.L.; Wardlaw, A.C.

1980-01-01

Bordetella pertussis has an absolute requirement for either nicotinic acid (NA) or nicotinamide (ND), both being equally effective in supporting growth. The results of an investigation to compare the rates of uptake of NA and ND, to determine the influence of factors such as energy source and temperature on uptake, and to measure the Ksub(m) and Vsub(max) values are reported. (Auth.)

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

Localized infusions of the partial alpha 7 nicotinic receptor agonist SSR180711 evoke rapid and transient increases in prefrontal glutamate release

DEFF Research Database (Denmark)

Bortz, D M; Mikkelsen, J D; Bruno, J P

2013-01-01

The ability of local infusions of the alpha 7 nicotinic acetycholine receptor (α7 nAChR) partial agonist SSR180711 to evoke glutamate release in prefrontal cortex was determined in awake rats using a microelectrode array. Infusions of SSR180711 produced dose-dependent increases in glutamate levels...

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.

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

Carbon-13 and oxygen-18 isotope effects in the decarboxylation of nicotinic acid of natural isotopic composition

International Nuclear Information System (INIS)

Zielinski, M.; Zielinska, A.; Papiernik-Zielinska, H.; McKenzie, J.A.; Bernasconi, S.; Paul, H.

1998-01-01

Carbon-13 and oxygen-18 isotope effects in the decarboxylation of nicotinic acid of natural isotopic composition above and below its melting temperature have been studied and compared with the primary (PKIE) and secondary kinetic isotope effects (SKIE) of 13 C and 18 O, respectively, in the decarboxylation of other heterocyclic acids. The temperature dependence of the secondary oxygen-18 isotope effects is negative in the total 221-255 deg C temperature interval investigated initially. The 13 C KIE measured above melting point of N.A. (temperature interval 235-270 deg C) are located in the range 1.007-1.009. Below melting point of nicotinic acid the 13 C KIE are larger and reveal the negative temperature dependence ( 13 C KIE decreases with decreasing the reaction temperature from 1.013/at 230 deg C to 1.0114/at 221 deg C). A discussion of the above isotopic results is presented. (author)

Engineering Escherichia coli Nicotinic Acid Mononucleotide Adenylyltransferase for Fully Active Amidated NAD Biosynthesis.

Science.gov (United States)

Wang, Xueying; Zhou, Yongjin J; Wang, Lei; Liu, Wujun; Liu, Yuxue; Peng, Chang; Zhao, Zongbao K

2017-07-01

NAD and its reduced form NADH function as essential redox cofactors and have major roles in determining cellular metabolic features. NAD can be synthesized through the deamidated and amidated pathways, for which the key reaction involves adenylylation of nicotinic acid mononucleotide (NaMN) and nicotinamide mononucleotide (NMN), respectively. In Escherichia coli , NAD de novo biosynthesis depends on the protein NadD-catalyzed adenylylation of NaMN to nicotinic acid adenine dinucleotide (NaAD), followed by NAD synthase-catalyzed amidation. In this study, we engineered NadD to favor NMN for improved amidated pathway activity. We designed NadD mutant libraries, screened by a malic enzyme-coupled colorimetric assay, and identified two variants, 11B4 (Y84V/Y118D) and 16D8 (A86W/Y118N), with a high preference for NMN. Whereas in the presence of NMN both variants were capable of enabling the viability of cells of E. coli BW25113-derived NAD-auxotrophic strain YJE003, for which the last step of the deamidated pathway is blocked, the 16D8 expression strain could grow without exogenous NMN and accumulated a higher cellular NAD(H) level than BW25113 in the stationary phase. These mutants established fully active amidated NAD biosynthesis and offered a new opportunity to manipulate NAD metabolism for biocatalysis and metabolic engineering. IMPORTANCE Adenylylation of nicotinic acid mononucleotide (NaMN) and adenylylation of nicotinamide mononucleotide (NMN), respectively, are the key steps in the deamidated and amidated pathways for NAD biosynthesis. In most organisms, canonical NAD biosynthesis follows the deamidated pathway. Here we engineered Escherichia coli NaMN adenylyltransferase to favor NMN and expressed the mutant enzyme in an NAD-auxotrophic E. coli strain that has the last step of the deamidated pathway blocked. The engineered strain survived in M9 medium, which indicated the implementation of a functional amidated pathway for NAD biosynthesis. These results enrich

Design, formulation and evaluation of nicotine chewing gum.

Science.gov (United States)

Aslani, Abolfazl; Rafiei, Sahar

2012-01-01

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

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.

Transdermal nicotine mixed natural rubber-hydroxypropylmethylcellulose film forming systems for smoking cessation: in vitro evaluations.

Science.gov (United States)

Pichayakorn, Wiwat; Suksaeree, Jirapornchai; Boonme, Prapaporn; Taweepreda, Wirach; Amnuaikit, Thanaporn; Ritthidej, Garnpimol C

2014-08-27

Abstract Novel film forming polymeric dispersions for transdermal nicotine delivery were prepared from deproteinized natural rubber latex (DNRL) blended with hydroxypropylmethylcellulose (HPMC) and dibutyl phthalate (DBP) or glycerin (GLY) as plasticizer. The preliminary molecular compatibility of ingredients was observed by Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry characterizations. All film forming polymeric dispersions were elegant in appearance and smooth in texture without agglomeration. Their pH was 7-8. In addition, their viscosity and spreadability showed good characteristics depended on HPMC and plasticizers blended. The transparent in situ dry films with good strength and elasticity were also confirmed by peeling-off. The nicotine release from them revealed an initial fast release that was similar to the release from a concentrated nicotine solution, and followed by slow release pattern from the in situ films. GLY blended formulation produced a higher amount of nicotine permeation through the in vitro pig skin than DBP blends. Ethanol mixing also enhanced nicotine permeation, but it affected the integrity of in situ films. The nicotine release and skin permeation kinetics were by a diffusion mechanism that was confirmed by the Higuchi's model. These formulations were safe without producing any severe skin irritation. However, for the stability they needed to be stored at 4 °C in tightly sealed containers.

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

Science.gov (United States)

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

2014-03-01

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

High-yield continuous production of nicotinic acid via nitrile hydratase–amidase cascade reactions using cascade CSMRs

Czech Academy of Sciences Publication Activity Database

Cantarella, L.; Gallifuoco, A.; Malandra, A.; Martínková, Ludmila; Spera, A.; Cantarella, M.

2011-01-01

Roč. 48, 4-5 (2011), 345-350 ISSN 0141-0229 R&D Projects: GA MŠk OC09046 Institutional research plan: CEZ:AV0Z50200510 Keywords : Nitrile hydratase-amidase cascade system * 3-Cyanopyridine bioconversion * Nicotinic acid Subject RIV: EE - Microbiology, Virology Impact factor: 2.367, year: 2011

Electrochemiluminescent determination of nicotine based on tri(2,2'-bipyridyl) ruthenium (II) complex through flow injection analysis

International Nuclear Information System (INIS)

Lin Mengshan; Wang Junsheng; Lai Chienhung

2008-01-01

This paper describes the electrogenerated chemiluminescence (ECL) processes of Ru(bpy) 3 2+ /nicotine system at ITO working electrode. An ECL-based method for rapid and sensitive detection of nicotine in phosphate buffer solution at pH 8.0 is established. Strong ECL emission was observed at a positive potential of 1.4 V vs. Ag/AgCl. A possible ECL mechanism is proposed for the Ru(bpy) 3 2+ /nicotine system, the oxidation product of nicotine at the electrode surface reacts with the 3+ state of ruthenium bipyridyl (2+) complex and form ruthenium complex exited state ions and thus releases photons. Effect of pH (medium/electrolyte), working potential, buffer composition, buffer concentration, reactant and co-reactant (nicotine) concentration, flow rate and loop size on the ECL spectrum of the Ru(bpy) 3 2+ /nicotine were studied. At the optimized experimental conditions, lower detection limit for nicotine was observed as 1.2 nmol L -1 (S/N = 3). Linear relationship between ECL current and concentration of nicotine was observed (up to 100 μmol L -1 ) with R-value of 0.997. The relative standard deviation with 5 μmol L -1 concentration of nicotine for 20 analyses was only 1.4%. A 94% recovery rate was observed in a real sample analysis without any complications/disturbance in measurement. Interferences of humid acid, camphor and SDS were not observed in their presence in the sample solution. The established procedure for nicotine quantification manifests fascinating results and can be suggested for further applications

Density and viscosity study of nicotinic acid and nicotinamide in dilute aqueous solutions at and around the temperature of the maximum density of water

International Nuclear Information System (INIS)

Dhondge, Sudhakar S.; Dahasahasra, Prachi N.; Paliwal, Lalitmohan J.; Deshmukh, Dinesh W.

2014-01-01

Highlights: • Volumetric and transport behaviour of aqueous solutions of important vitamins are reported. • Various interactions of nicotinic acid and nicotinamide with water have been reported. • The temperature dependence of interactions between solute and solvent is discussed. • The study indicates that nicotinamide is more hydrated as compared to nicotinic acid. - Abstract: In the present study, we report experimental densities (ρ) and viscosities (η) of aqueous solutions of nicotinic acid and nicotinamide within the concentration range (0 to 0.1) mol · kg −1 at T = (275.15, 277.15 and 279.15) K. These parameters are then used to obtain thermodynamic and transport functions such as apparent molar volume of solute (V ϕ ), limiting apparent molar volume of solute (V ϕ 0 ), limiting apparent molar expansivity of solute (E ϕ 0 ), coefficient of thermal expansion (α ∗ ), Jones–Dole equation viscosity A, B and D coefficients, temperature derivative of B coefficient i.e. (dB/dT) and hydration number (n H ), etc. The activation parameters of viscous flow for the binary mixtures have been determined and discussed in terms of Eyring’s transition state theory. These significant parameters are helpful to study the structure promoting or destroying tendency of solute and various interactions present in (nicotinic acid + water) and (nicotinamide + water) binary mixtures

Fluoride release from fluoride varnishes under acidic conditions.

Science.gov (United States)

Lippert, F

2014-01-01

The aim was to investigate the in vitro fluoride release from fluoride varnishes under acidic conditions. Poly(methyl methacrylate) blocks (Perspex, n=3 per group) were painted with 80 ± 5 mg fluoride varnish (n=10) and placed into artificial saliva for 30 min. Then, blocks were placed into either 1% citric acid (pH 2.27) or 0.3% citric acid (pH 3.75) solutions (n=3 per solution and varnish) for 30 min with the solutions being replaced every 5 min. Saliva and acid solutions were analyzed for fluoride content. Data were analyzed using three-way ANOVA (varnish, solution, time). The three-way interaction was significant (p>0.0001). Fluoride release and release patterns varied considerably between varnishes. Fluoride release in saliva varied by a factor of more than 10 between varnishes. Some varnishes (CavityShield, Nupro, ProFluorid, Vanish) showed higher fluoride release in saliva than during the first 5 min of acid exposure, whereas other varnishes (Acclean, Enamel-Pro, MI Varnish, Vella) showed the opposite behavior. There was little difference between acidic solutions. Fluoride release from fluoride varnishes varies considerably and also depends on the dissolution medium. Bearing in mind the limitations of laboratory research, the consumption of acidic drinks after fluoride varnish application should be avoided to optimize the benefit/risk ratio.

Microbial production of squalene by a nicotinic acid-resistant mutant derived from Fusarium sp. No.5-128B

International Nuclear Information System (INIS)

Ogawa, T.; Kojima, I.; Takeda, N.; Fukuda, H.

1994-01-01

A nicotinic acid-resistant mutant, designated NA201, was obtained from Fusarium sp. no.5-128B by treatment with ultraviolet light. This mutant strain could grow in the presence of up to 500mM nicotinic acid in the culture medium, although the parent strain could not grow at concentrations of nicotinic acid above 200 mM. The Na201 strain exhibited morphological mutations, neither forming aerial hyphae nor secreting a red-brown pigment. However, it retained the resistance to kabicidin at 25 mg-l(-1) of the parent strain. The mutant NA201 cells contained high levels of squalene and low levels of ergosterol, about 53 times higher and five to six times lower, respectively, than those of the parent strain under standard culture conditions. The volumetric oxygen transfer coefficient (Kd) affected the level of squalene in the mutant cells. The Kd for the maximum production of squalene by the mutant was 24 mmol O2 l(-1)h(-1)atm(-1) and the level of squalene in the mutant cells was 26 mg (g cell)(-1) on a dry weight basis. The greatest accumulation of squalene by the Na201 strain, corresponding to 323 mg per liter of culture medium and 35 mg (g cell)(-1) on a dry weight basis, was achieved in a culture in which the Kd was changed from a high to a low value on the third day, with the simultaneous addition of 3% glucose (w/v)

Littered cigarette butts as a source of nicotine in urban waters

Science.gov (United States)

Roder Green, Amy L.; Putschew, Anke; Nehls, Thomas

2014-11-01

The effect of nicotine from littered cigarette butts on the quality of urban water resources has yet to be investigated. This two-part study addresses the spatial variation, seasonal dynamics and average residence time of littered cigarette butts in public space, as well as the release of nicotine from cigarette butts to run-off in urban areas during its residence time. Thereby, we tested two typical situations: release to standing water in a puddle and release during alternating rainfall and drying. The study took place in Berlin, Germany, a city which completely relies on its own water resources to meet its drinking water demand. Nine typical sites located in a central district, each divided into 20 plots were studied during five sampling periods between May 2012 and February 2013. The nicotine release from standardized cigarette butts prepared with a smoking machine was examined in batch and rainfall experiments. Littered cigarette butts are unevenly distributed among both sites and plots. The average butt concentration was 2.7 m-2 (SD = 0.6 m-2, N = 862); the maximum plot concentration was 48.8 butts m-2. This heterogeneity is caused by preferential littering (gastronomy, entrances, bus stops), redistribution processes such as litter removal (gastronomy, shop owners), and the increased accumulation in plots protected from mechanized street sweeping (tree pits, bicycle stands). No significant seasonal variation of cigarette butt accumulation was observed. On average, cigarette butt accumulation is characterized by a 6 days cadence due to the rhythm and effectiveness of street sweeping (mean weekly butt accumulation rate = 0.18 m-2 d-1; SD = 0.15 m-1). Once the butt is exposed to standing water, elution of nicotine occurs rapidly. Standardized butts released 7.3 mg g-1 nicotine in a batch experiment (equivalent to 2.5 mg L-1), 50% of which occurred within the first 27 min. In the rainfall experiment, the cumulative nicotine release from fifteen consecutive

Electrochemiluminescent determination of nicotine based on tri(2,2'-bipyridyl) ruthenium (II) complex through flow injection analysis

Energy Technology Data Exchange (ETDEWEB)

Lin Mengshan [Department of Chemistry, Tamkang University, Tamsui 25137, Taiwan (China)], E-mail: mslin@mail.tku.edu.tw; Wang Junsheng; Lai Chienhung [Department of Chemistry, Tamkang University, Tamsui 25137, Taiwan (China)

2008-11-01

This paper describes the electrogenerated chemiluminescence (ECL) processes of Ru(bpy){sub 3}{sup 2+}/nicotine system at ITO working electrode. An ECL-based method for rapid and sensitive detection of nicotine in phosphate buffer solution at pH 8.0 is established. Strong ECL emission was observed at a positive potential of 1.4 V vs. Ag/AgCl. A possible ECL mechanism is proposed for the Ru(bpy){sub 3}{sup 2+}/nicotine system, the oxidation product of nicotine at the electrode surface reacts with the 3+ state of ruthenium bipyridyl (2+) complex and form ruthenium complex exited state ions and thus releases photons. Effect of pH (medium/electrolyte), working potential, buffer composition, buffer concentration, reactant and co-reactant (nicotine) concentration, flow rate and loop size on the ECL spectrum of the Ru(bpy){sub 3}{sup 2+}/nicotine were studied. At the optimized experimental conditions, lower detection limit for nicotine was observed as 1.2 nmol L{sup -1} (S/N = 3). Linear relationship between ECL current and concentration of nicotine was observed (up to 100 {mu}mol L{sup -1}) with R-value of 0.997. The relative standard deviation with 5 {mu}mol L{sup -1} concentration of nicotine for 20 analyses was only 1.4%. A 94% recovery rate was observed in a real sample analysis without any complications/disturbance in measurement. Interferences of humid acid, camphor and SDS were not observed in their presence in the sample solution. The established procedure for nicotine quantification manifests fascinating results and can be suggested for further applications.

Electrochemiluminescent determination of nicotine based on tri(2,2'-bipyridyl) ruthenium (II) complex through flow injection analysis

Energy Technology Data Exchange (ETDEWEB)

Lin, Meng Shan; Wang, Jun Sheng; Lai, Chien Hung [Department of Chemistry, Tamkang University, Tamsui 25137 (China)

2008-11-01

This paper describes the electrogenerated chemiluminescence (ECL) processes of Ru(bpy){sub 3}{sup 2+}/nicotine system at ITO working electrode. An ECL-based method for rapid and sensitive detection of nicotine in phosphate buffer solution at pH 8.0 is established. Strong ECL emission was observed at a positive potential of 1.4 V vs. Ag/AgCl. A possible ECL mechanism is proposed for the Ru(bpy){sub 3}{sup 2+}/nicotine system, the oxidation product of nicotine at the electrode surface reacts with the 3+ state of ruthenium bipyridyl (2+) complex and form ruthenium complex exited state ions and thus releases photons. Effect of pH (medium/electrolyte), working potential, buffer composition, buffer concentration, reactant and co-reactant (nicotine) concentration, flow rate and loop size on the ECL spectrum of the Ru(bpy){sub 3}{sup 2+}/nicotine were studied. At the optimized experimental conditions, lower detection limit for nicotine was observed as 1.2 nmol L{sup -1} (S/N = 3). Linear relationship between ECL current and concentration of nicotine was observed (up to 100 {mu}mol L{sup -1}) with R-value of 0.997. The relative standard deviation with 5 {mu}mol L{sup -1} concentration of nicotine for 20 analyses was only 1.4%. A 94% recovery rate was observed in a real sample analysis without any complications/disturbance in measurement. Interferences of humid acid, camphor and SDS were not observed in their presence in the sample solution. The established procedure for nicotine quantification manifests fascinating results and can be suggested for further applications. (author)

Molecular evolution of the nicotinic acid requirement within the Shigella/EIEC pathotype.

Science.gov (United States)

Di Martino, Maria Letizia; Fioravanti, Rosa; Barbabella, Giada; Prosseda, Gianni; Colonna, Bianca; Casalino, Mariassunta

2013-12-01

Nicotinamide adenine dinucleotide (NAD) is a crucial cofactor in several anabolic and catabolic reactions. NAD derives from quinolinic acid (QUIN) which in Escherichia coli is obtained through a pyridine salvage pathway or a de novo synthesis pathway. In the latter case, two enzymes, L-aspartate oxidase (NadB) and quinolinate synthase (NadA), are required for the synthesis of QUIN. In contrast to its E. coli ancestor, Shigella spp., the causative agent of bacillary dissentery, lacks the de novo pathway and strictly requires nicotinic acid for growth (Nic⁻ phenotype). This phenotype depends on the silencing of the nadB and nadA genes and its pathoadaptive nature is suggested by the observation that QUIN attenuates the Shigella invasive process. Shigella shares the pathogenicity mechanism with enteronvasive E. coli (EIEC), a group of pathogenic E. coli. On the basis of this similarity EIEC and Shigella have been grouped into a single E. coli pathotype. However EIEC strains do not constitute a homogeneous group and do not possess the complete set of characters that define Shigella strains. In this work we have analysed thirteen EIEC strains belonging to different serotypes and originating from different geographic areas. We show that, in contrast to Shigella, only some EIEC strains require nicotinic acid for growth in minimal medium. Moreover, by studying the emergence of the Nic⁻ phenotype in all serotypes of S. flexneri, as well as in S. sonnei and S. dysenteriae, we describe which molecular rearrangements occurred and which mutations are responsible for the inactivation of the nadA and nadB genes. Our data confirm that the genome of Shigella is extremely dynamic and support the hypothesis that EIEC might reflect an earlier stage of the pathoadaptation process undergone by Shigella. Copyright © 2013. Published by Elsevier GmbH.

'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

Effects of solvent and structure on the reactivity of 6-substituted nicotinic acids with diazodiphenylmethane in aprotic solvents

Directory of Open Access Journals (Sweden)

BRATISLAV Ž. JOVANOVIĆ

2009-12-01

Full Text Available The rate constants for the reactions of diazodiphenylmethane (DDM with 6-substituted nicotinic acids in aprotic solvents at 30 °C were determined. The obtained second order rate constants in aprotic solvents, together with literature data for benzoic and nicotinic acids in protic solvents, were used for the calculation of solvent effects, employing the Kamlet-Taft solvatochromic equation (linear solvation energy relationship – LSER in the form: log k = log k0 + s* + a + b. The correlations of the kinetic data were performed by means of multiple linear regression analysis taking appropriate solvent parameters. The sign of the equation coefficients (s, a and b were in agreement with the postulated reaction mechanism, and the mode of the solvent influences on the reaction rate is discussed based on the correlation results. A similar contribution of the non-specific solvent effect and electrophilic solvation was observed for all acids, while the highest contribution of nucleophilic solvation was influenced by their high acidity. Correlation analysis of the rate data with substituent p parameters in an appropriate solvent using the Hammett equation was also performed. The substituent effect on the acid reactivity was higher in aprotic solvents of higher dipolarity/polarizability. The mode of the transmission of the substituent effect is discussed in light of the contribution of solute–solvent interaction on the acid reactivity.

Differential sensitivity to nicotine among hypothalamic magnocellular neurons

DEFF Research Database (Denmark)

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

2012-01-01

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

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.

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.

Heat capacity and thermodynamics of solid and liquid pyridine-3-carboxylic acid (nicotinic acid) over the temperature range 296 K to 531 K

International Nuclear Information System (INIS)

Joseph, Abhinav; Bernardes, Carlos E.S.; Minas da Piedade, Manuel E.

2012-01-01

Highlights: ► We determined the heat capacity of solid and liquid nicotinic acid by DSC. ► We determined Δ 357.8K 305.6K H m o (NA,crII) by Calvet microcalorimetry. ► We studied the thermodynamics of the cr II → cr I phase transition. ► We determined the Δ f G m o –T diagram of nicotinic acid for T = (296 to 531) K. - Abstract: The molar heat capacity of pyridine-3-carboxylic acid (nicotinic acid) for T = (296 to 531) K was investigated by differential scanning calorimetry (DSC) and Calvet-drop microcalorimetry. The measurements extended up to the liquid range and also covered the interval where a reversible and fast solid-solid (cr II → cr I) phase transition occurs. The molar enthalpies and entropies of that phase transition and of fusion were obtained as T trs = (455.0 ± 0.2) K, Δ trs H m o = (0.90 ± 0.10) kJ ⋅ mol −1 , Δ trs S m o = (1.98 ± 0.22) J ⋅ K −1 ⋅ mol −1 , T fus = (509.91 ± 0.04) K, Δ fus H m o = (28.2 ± 0.1) kJ ⋅ mol −1 , and Δ fus S m o = (55.30 ± 0.16) J ⋅ K −1 ⋅ mol −1 . By combining these experimental results with the previously reported Δ sub H m (NA,cr II) at T = 366.5 K, the corresponding entropy in the gaseous state calculated at the B3LYP/6-31+G(d,p) level of theory, and Δ f H m o (NA),cr II) at T = 298.15 K, it was possible to estimate the standard molar Gibbs energy of formation functions necessary for the construction of the Δ f G m ∘ vs. T diagram illustrating the enantiotropic nature of this system.

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.

Human adipose tissue blood flow during prolonged exercise, III. Effect of beta-adrenergic blockade, nicotinic acid and glucose infusion

DEFF Research Database (Denmark)

Bülow, J

1981-01-01

Subcutaneous adipose tissue blood flow (ATBF) was measured in six male subjects by the 133Xe-washout technique during 3-4 h of exercise at a work load corresponding to an oxygen uptake of about 1.71/min. The measurements were done during control conditions, during blockade of lipolysis by nicotinic...... of work. No increase in lipolysis and no increase in ATBF were found when lipolysis was blocked by nicotinic acid (0.3 g/h). Propranolol treatment (0.15 mg/kg) reduced lipolysis and nearly abolished the increase in ATBF during exercise. Intravenous administration of glucose (about 0.25 g/min) did...

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...

Human adipose tissue blood flow during prolonged exercise, III. Effect of beta-adrenergic blockade, nicotinic acid and glucose infusion

DEFF Research Database (Denmark)

Bülow, J

1981-01-01

acid, during acute i.v. beta-adrenergic blockade by propranolol, and during continuous i.v. infusion of glucose. The most pronounced lipid mobilization and utilization during work was seen in the control experiments where ATBF rose 3-fold on average from the initial rest period to the third hour...... of work. No increase in lipolysis and no increase in ATBF were found when lipolysis was blocked by nicotinic acid (0.3 g/h). Propranolol treatment (0.15 mg/kg) reduced lipolysis and nearly abolished the increase in ATBF during exercise. Intravenous administration of glucose (about 0.25 g/min) did......Subcutaneous adipose tissue blood flow (ATBF) was measured in six male subjects by the 133Xe-washout technique during 3-4 h of exercise at a work load corresponding to an oxygen uptake of about 1.71/min. The measurements were done during control conditions, during blockade of lipolysis by nicotinic...

Novel Caffeic Acid Nanocarrier: Production, Characterization, and Release Modeling

Directory of Open Access Journals (Sweden)

Milad Fathi

2013-01-01

Full Text Available This paper deals with the development of novel nanocarriers using layer by layer carbohydrate coating of caffeic acid loaded solid lipid nanoparticles (SLNs to improve stability and colon delivery of the poorly water-soluble caffeic acid. Three biopolymers (chitosan, alginate, and pectin in different concentrations (0.1, 0.25, and 0.5% were electrostatically coated over the SLN surface. The size and zeta potential of produced nanocarriers were measured using photon correlation spectroscopy. Mathematical models (i.e., zero-order, first-order, Higuchi, Ritger-Peppas, reciprocal powered time, Weibull, and quadratic models were used to describe the release and kinetic modeling in gastrointestinal solution (GIS. Also, antioxidant activity of caffeic acid during the release in GIS was investigated using DPPH and reducing activity methods. The prepared treatments coated by alginate-chitosan as well as pectin-chitosan coated SLN at the concentration of 0.1% showed nanosized bead; the latter efficiently retarded the release of caffeic acid in gastric media up to 2.5 times higher than that of SLN. Zeta potential values of coated samples were found to significantly increase in comparison to SLN indicating the higher stability of produced nanocarriers. Antioxidant activity of caffeic acid after gastric release did not result in the same trend as observed for caffeic acid release from different treatments; however, in line with less caffeic acid release in the intestine solution by the effect of coating, lower antioxidant activity was determined at the end stage of the experiment.

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.

Effect of Oxidative Phytochemicals on Nicotine-stressed UMNSAH/DF-1 Cell Line

Directory of Open Access Journals (Sweden)

Amlan Chakraborty

2014-04-01

Full Text Available Nicotine is a parasympathomimetic alkaloid found in the nightshade family of plants (Solanaceae and is a cholinergic drug. It acts directly by stimulating the nicotinic or muscarinic receptors or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or by other mechanisms. 3% of tobacco or one cigarette yields 1 mg of nicotine. As nicotine enters the body, it disturbs the healthy functioning of the body. In this study, we isolated UMNSAH/DF-1 cell line from Gallus gallus. For this, 9±2 day old chicken embryo was taken. This was followed by the extraction of nicotine (1 mg/ml from cigarette. The cells were then given nicotine stress and were observed for blackening after 24 h of incubation under 40× resolution of microscope. It was found that this blackening of the cells was permanent even after a wash with 1× phosphate-buffered saline (PBS followed by replenishing the medium. The phytochemicals extracted were from the dried powder, which included Curcuma longa (薑黃 Jiāng Huáng; Turmeric 40 mg/ml, Azadirachta indica (neem 50 mg/ml, Cinnamomum tamala (bay leaf 30 mg/ml, Camellia sinensis (綠茶 Lǜ Chá; Green Tea 100 mg/ml, and Ocimum sanctum (tulsi 30 mg/ml. When applied to nicotine-stressed cells, it was observed that ursolic acid in neem recovered 70%, followed by 65% recovery by tulsi (having triterpenoid, 50% recovery by the catechins in Ca. sinensis, and very little recovery shown by Ci. tamala. Due to the yellow coloration of the cells by Cu. longa, much could not be inferred, although it was inferable that it had resulted in little effects. Mixtures of these phytochemicals were used, and it was found that neem: tulsi diluted in 3:1 ratio was highly effective and cell recovery was almost 80%. 68% was recovered by tulsi: green tea in a ratio 1:3 and 42% by turmeric:green tea in a ratio of 1:5.

Conversion of nicotinic acid to trigonelline is catalyzed by N-methyltransferase belonged to motif B′ methyltransferase family in Coffea arabica

International Nuclear Information System (INIS)

Mizuno, Kouichi; Matsuzaki, Masahiro; Kanazawa, Shiho; Tokiwano, Tetsuo; Yoshizawa, Yuko; Kato, Misako

2014-01-01

Graphical abstract: Trigonelline synthase catalyzes the conversion of nicotinic acid to trigonelline. We isolated and characterized trigonelline synthase gene(s) from Coffea arabica. - Highlights: • Trigonelline is a major compound in coffee been same as caffeine is. • We isolated and characterized trigonelline synthase gene. • Coffee trigonelline synthases are highly homologous with coffee caffeine synthases. • This study contributes the fully understanding of pyridine alkaloid metabolism. - Abstract: Trigonelline (N-methylnicotinate), a member of the pyridine alkaloids, accumulates in coffee beans along with caffeine. The biosynthetic pathway of trigonelline is not fully elucidated. While it is quite likely that the production of trigonelline from nicotinate is catalyzed by N-methyltransferase, as is caffeine synthase (CS), the enzyme(s) and gene(s) involved in N-methylation have not yet been characterized. It should be noted that, similar to caffeine, trigonelline accumulation is initiated during the development of coffee fruits. Interestingly, the expression profiles for two genes homologous to caffeine synthases were similar to the accumulation profile of trigonelline. We presumed that these two CS-homologous genes encoded trigonelline synthases. These genes were then expressed in Escherichiacoli, and the resulting recombinant enzymes that were obtained were characterized. Consequently, using the N-methyltransferase assay with S-adenosyl[methyl- 14 C]methionine, it was confirmed that these recombinant enzymes catalyzed the conversion of nicotinate to trigonelline, coffee trigonelline synthases (termed CTgS1 and CTgS2) were highly identical (over 95% identity) to each other. The sequence homology between the CTgSs and coffee CCS1 was 82%. The pH-dependent activity curve of CTgS1 and CTgS2 revealed optimum activity at pH 7.5. Nicotinate was the specific methyl acceptor for CTgSs, and no activity was detected with any other nicotinate derivatives, or with

Conversion of nicotinic acid to trigonelline is catalyzed by N-methyltransferase belonged to motif B′ methyltransferase family in Coffea arabica

Energy Technology Data Exchange (ETDEWEB)

Mizuno, Kouichi, E-mail: koumno@akita-pu.ac.jp [Faculty of Bioresource Sciences, Akita Prefectural University, Akita City, Akita 010-0195 (Japan); Matsuzaki, Masahiro [Faculty of Bioresource Sciences, Akita Prefectural University, Akita City, Akita 010-0195 (Japan); Kanazawa, Shiho [Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo 112-8610 (Japan); Tokiwano, Tetsuo; Yoshizawa, Yuko [Faculty of Bioresource Sciences, Akita Prefectural University, Akita City, Akita 010-0195 (Japan); Kato, Misako [Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo 112-8610 (Japan)

2014-10-03

Graphical abstract: Trigonelline synthase catalyzes the conversion of nicotinic acid to trigonelline. We isolated and characterized trigonelline synthase gene(s) from Coffea arabica. - Highlights: • Trigonelline is a major compound in coffee been same as caffeine is. • We isolated and characterized trigonelline synthase gene. • Coffee trigonelline synthases are highly homologous with coffee caffeine synthases. • This study contributes the fully understanding of pyridine alkaloid metabolism. - Abstract: Trigonelline (N-methylnicotinate), a member of the pyridine alkaloids, accumulates in coffee beans along with caffeine. The biosynthetic pathway of trigonelline is not fully elucidated. While it is quite likely that the production of trigonelline from nicotinate is catalyzed by N-methyltransferase, as is caffeine synthase (CS), the enzyme(s) and gene(s) involved in N-methylation have not yet been characterized. It should be noted that, similar to caffeine, trigonelline accumulation is initiated during the development of coffee fruits. Interestingly, the expression profiles for two genes homologous to caffeine synthases were similar to the accumulation profile of trigonelline. We presumed that these two CS-homologous genes encoded trigonelline synthases. These genes were then expressed in Escherichiacoli, and the resulting recombinant enzymes that were obtained were characterized. Consequently, using the N-methyltransferase assay with S-adenosyl[methyl-{sup 14}C]methionine, it was confirmed that these recombinant enzymes catalyzed the conversion of nicotinate to trigonelline, coffee trigonelline synthases (termed CTgS1 and CTgS2) were highly identical (over 95% identity) to each other. The sequence homology between the CTgSs and coffee CCS1 was 82%. The pH-dependent activity curve of CTgS1 and CTgS2 revealed optimum activity at pH 7.5. Nicotinate was the specific methyl acceptor for CTgSs, and no activity was detected with any other nicotinate derivatives, or

The Distribution of Charged Amino Acid Residues and the Ca2+ Permeability of Nicotinic Acetylcholine Receptors: A Predictive Model

Directory of Open Access Journals (Sweden)

Sergio Fucile

2017-05-01

Full Text Available Nicotinic acetylcholine receptors (nAChRs are cation-selective ligand-gated ion channels exhibiting variable Ca2+ permeability depending on their subunit composition. The Ca2+ permeability is a crucial functional parameter to understand the physiological role of nAChRs, in particular considering their ability to modulate Ca2+-dependent processes such as neurotransmitter release. The rings of extracellular and intracellular charged amino acid residues adjacent to the pore-lining TM2 transmembrane segment have been shown to play a key role in the cation selectivity of these receptor channels, but to date a quantitative relationship between these structural determinants and the Ca2+ permeability of nAChRs is lacking. In the last years the Ca2+ permeability of several nAChR subtypes has been experimentally evaluated, in terms of fractional Ca2+ current (Pf, i.e., the percentage of the total current carried by Ca2+ ions. In the present study, the available Pf-values of nAChRs are used to build a simplified modular model describing the contribution of the charged residues in defined regions flanking TM2 to the selectivity filter controlling Ca2+ influx. This model allows to predict the currently unknown Pf-values of existing nAChRs, as well as the hypothetical Ca2+ permeability of subunit combinations not able to assemble into functional receptors. In particular, basing on the amino acid sequences, a Pf > 50% would be associated with homomeric nAChRs composed by different α subunits, excluding α7, α9, and α10. Furthermore, according to the model, human α7β2 receptors should have Pf-values ranging from 3.6% (4:1 ratio to 0.1% (1:4 ratio, much lower than the 11.4% of homomeric α7 nAChR. These results help to understand the evolution and the function of the large diversity of the nicotinic receptor family.

Photocuring of stimulus responsive membranes for controlled-release of drugs having different molecular weights

International Nuclear Information System (INIS)

Ng, Loo-Teck; Nakayama, Hiroshi; Kaetsu, Isao; Uchida, Kumao

2005-01-01

Intelligent drug delivery membranes were prepared by photocuring poly(acrylic acid) coatings onto poly(2-hydroxyethyl methacrylate) membranes each with model drugs of different molecular weights being incorporated. pH-responsive release behaviours of the model drugs which included sodium salicylate, nicotinamide, nicotinic acid, methylene blue, brilliant green and crystal violet were investigated. Only the membrane with methylene blue incorporated showed a clear pH-responsive release and other drug-incorporated membranes showed no intelligent behaviour. These phenomena were explained in terms of the difference in diffusivity of drugs through polymer matrices of the membranes attributable to the difference in the molecular weights of drugs

Photocuring of stimulus responsive membranes for controlled-release of drugs having different molecular weights

Energy Technology Data Exchange (ETDEWEB)

Ng, Loo-Teck [School of Science, Food and Horticulture, University of Western Sydney, Locked bag 1797, Penrith South DC, NSW 1797 (Australia)]. E-mail: l.ng@uws.edu.au; Nakayama, Hiroshi [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan); Kaetsu, Isao [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan)]. E-mail: kaetsu@ned.kindai.ac.jp; Uchida, Kumao [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan)

2005-06-01

Intelligent drug delivery membranes were prepared by photocuring poly(acrylic acid) coatings onto poly(2-hydroxyethyl methacrylate) membranes each with model drugs of different molecular weights being incorporated. pH-responsive release behaviours of the model drugs which included sodium salicylate, nicotinamide, nicotinic acid, methylene blue, brilliant green and crystal violet were investigated. Only the membrane with methylene blue incorporated showed a clear pH-responsive release and other drug-incorporated membranes showed no intelligent behaviour. These phenomena were explained in terms of the difference in diffusivity of drugs through polymer matrices of the membranes attributable to the difference in the molecular weights of drugs.

Serotonergic modulation of nicotine-induced kinetic tremor in mice.

Science.gov (United States)

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

2017-06-01

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

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

Science.gov (United States)

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

Nicotine 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.

Activation and regulation of arachidonic acid release in rabbit peritoneal neutrophils

International Nuclear Information System (INIS)

Tao, W.

1988-01-01

Arachidonic acid release in rabbit neutrophils can be enhanced by the addition of chemotactic fMet-Leu-Phe, platelet-activating factor, PAF, or the calcium ionophore A23187. Over 80% of the release [ 3 H]arachidonic acid comes from phosphatidylcholine and phosphatidylinositol. The release is dose-dependent and increases with increasing concentration of the stimulus. The A23187-induced release increases with increasing time of the stimulation. [ 3 H]arachidonic acid release, but not the rise in the concentration of intracellular calcium, is inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The [ 3 H]arachidonic acid released by A23187 is potentiated while that release by fMET-Leu-Phe or PAF is inhibited in phorbol 12-myristate 13-acetate, PMA, treated rabbit neutrophils. The protein kinase C inhibitor 1-(5-isoquinoline sulfonyl)-2-methylpiperazine, H-7, has no effect on the potentiation by PMA of the A23187-induced release, it prevents the inhibition by PMA of the release produced by PAF or fMet-Leu-Phe. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. The diacylglycerol kinase inhibitor R59022 increases the level of diacylglycerol in neutrophils stimulated with fMet-Leu-Phe. Furthermore, R59022 potentiates [ 3 H] arachidonic acid release produced by fMet-Leu-Phe. This potentiation is not inhibited by H-7, in fact, it is increased in H-7-treated neutrophils

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

Science.gov (United States)

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

2014-03-01

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

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.

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.

[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

Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

Directory of Open Access Journals (Sweden)

Paul Fredrickson

2014-01-01

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

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.

A rapid microwave induced synthesis of [carboxyl-14C]-nicotinic acid (vitamin B3) and [carbonyl-14C]-nicotinamide using K14CN

International Nuclear Information System (INIS)

Ravi, S.; Mathew, K.M.; Sivaprasad, N.

2008-01-01

Microwave assisted direct aromatic substitution of 3-bromopyridine with K 14 CN as the cyanide source and catalytic amount of tetrabutylammonium bromide afforded [3- 14 C]-cyanopyridine 3 in 90% yield. Microwave assisted hydrolysis of 3 with a mixture of concentrated hydrochloric acid and propionic acid afforded [carboxyl- 14 C]-nicotinic acid in 95% yield whereas microwave assisted hydrolysis of 3 with a mixture of concentrated sulfuric acid and propionic acid afforded [carbonyl- 14 C]-nicotinamide in 85% yield. (author)

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.

Use of nicotinic acid and midocalm to correct hemocoagulation in patients with radiation edema of the limbs

International Nuclear Information System (INIS)

Chekalina, S.I.; Guseva, L.I.; Bardychev, M.S.

1985-01-01

A study was made of the functional activity of blood platelets, plasma coagulation and fibrinolysis in patients with late radiation injuries of the blood and lymph flow during treatment with vasodilative drugs: nicotinic acid and midocalm. These drugs tend to decrease the functional activity of blood platelets and to raise the blood fibrinolytic activity. Their use is indicated to this group of patients to better their intravascular status

Ethyl cellulose microcapsules for protecting and controlled release of folic acid.

Science.gov (United States)

Prasertmanakit, Satit; Praphairaksit, Nalena; Chiangthong, Worawadee; Muangsin, Nongnuj

2009-01-01

Ethyl cellulose microcapsules were developed for use as a drug-delivery device for protecting folic acid from release and degradation in the undesirable environmental conditions of the stomach, whilst allowing its release in the intestinal tract to make it available for absorption. The controlled release folic acid-loaded ethyl cellulose microcapsules were prepared by oil-in-oil emulsion solvent evaporation using a mixed solvent system, consisting of a 9:1 (v/v) ratio of acetone:methanol and light liquid paraffin as the dispersed and continuous phase. Span 80 was used as the surfactant to stabilize the emulsion. Scanning electron microscopy revealed that the microcapsules had a spherical shape. However, the particulate properties and in vitro release profile depended on the concentrations of the ethyl cellulose, Span 80 emulsifier, sucrose (pore inducer), and folic acid. The average diameter of the microcapsules increased from 300 to 448 microm, whilst the folic acid release rate decreased from 52% to 40%, as the ethyl cellulose concentration was increased from 2.5% to 7.5% (w/v). Increasing the Span 80 concentration from 1% to 4% (v/v) decreased the average diameter of microcapsules from 300 to 141 microm and increased the folic acid release rate from 52% to 79%. The addition of 2.5-7.5% (w/v) of sucrose improved the folic acid release from the microcapsules. The entrapment efficiency was improved from 64% to 88% when the initial folic acid concentration was increased from 1 to 3 mg/ml.

Influence of Citric Acid on the Metal Release of Stainless Steels

Energy Technology Data Exchange (ETDEWEB)

Mazinanian, N.; Wallinder, I. Odnevall; Hedberg, Y. S. [KTH Royal Institute of Technology, School of Chemical Science and Engineering, Department of Chemistry, Division of Surface and Corrosion Science, Stockholm (Sweden)

2015-08-15

Knowledge of how metal releases from the stainless steels used in food processing applications and cooking utensils is essential within the framework of human health risk assessment. A new European standard test protocol for testing metal release in food contact materials made from metals and alloys has recently been published by the Council of Europe. The major difference from earlier test protocols is the use of citric acid as the worst-case food simulant. The objectives of this study were to assess the effect of citric acid at acidic, neutral, and alkaline solution pH on the extent of metal release for stainless steel grades AISI 304 and 316, commonly used as food contact materials. Both grades released lower amounts of metals than the specific release limits when they were tested according to test guidelines. The released amounts of metals were assessed by means of graphite furnace atomic absorption spectroscopy, and changes in the outermost surface composition were determined using X-ray photoelectron spectroscopy. The results demonstrate that both the pH and the complexation capacity of the solutions affected the extent of metal release from stainless steel and are discussed from a mechanistic perspective. The outermost surface oxide was significantly enriched in chromium upon exposure to citric acid, indicating rapid passivation by the acid. This study elucidates the effect of several possible mechanisms, including complex ion- and ligand-induced metal release, that govern the process of metal release from stainless steel under passive conditions in solutions that contain citric acid.

Cystoid Macular Edema Induced by Low Doses of Nicotinic Acid

Directory of Open Access Journals (Sweden)

Daniela Domanico

2013-01-01

Full Text Available Cystoid macular edema (CME is a condition that involves the macula, causing painless vision loss. In this paper, we report a case of niacin-induced bilateral cystoid macular edema (CME in a middle-age woman taking low dose of niacin (18 mg of nicotinic acid. Optical coherence tomography (OCT showed retinal thickening and cystoid spaces in both eyes, whereas fluorescein angiography (FA; HRA 2, Heidelberg Engineering revealed the absence of fluorescein leakage also in later phases. Four weeks after discontinuation of therapy there were a complete disappearance of macular edema at funduscopic examination and an improvement of visual acuity in both eyes. Furthermore OCT showed a normal retinal profile in both eyes. In our opinion considering the wide availability of niacin, medical monitoring and periodical examination should be considered during niacin administration. To our knowledge, this is the first report in the literature that described the very low-dose niacin-induced bilateral niacin maculopathy.

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

Presynaptic nicotinic α7 and non-α7 receptors stimulate endogenous GABA release from rat hippocampal synaptosomes through two mechanisms of action.

Directory of Open Access Journals (Sweden)

Stefania Zappettini

Full Text Available BACKGROUND: Although converging evidence has suggested that nicotinic acetylcholine receptors (nAChR play a role in the modulation of GABA release in rat hippocampus, the specific involvement of different nAChR subtypes at presynaptic level is still a matter of debate. In the present work we investigated, using selective α7 and α4β2 nAChR agonists, the presence of different nAChR subtypes on hippocampal GABA nerve endings to assess to what extent and through which mechanisms they stimulate endogenous GABA release. METHODOLOGY/FINDINGS: All agonists elicited GABA overflow. Choline (Ch-evoked GABA overflow was dependent to external Ca(2+, but unaltered in the presence of Cd(2+, tetrodotoxin (TTX, dihydro-β-erythroidine (DHβE and 1-(4,4-Diphenyl-3-butenyl-3-piperidinecarboxylic acid hydrochloride SKF 89976A. The effect of Ch was blocked by methyllycaconitine (MLA, α-bungarotoxin (α-BTX, dantrolene, thapsigargin and xestospongin C, suggesting that GABA release might be triggered by Ca(2+ entry into synaptosomes through the α7 nAChR channel with the involvement of calcium from intracellular stores. Additionally, 5-Iodo-A-85380 dihydrochloride (5IA85380 elicited GABA overflow, which was Ca(2+ dependent, blocked by Cd(2+, and significantly inhibited by TTX and DHβE, but unaffected by MLA, SKF 89976A, thapsigargin and xestospongin C and dantrolene. These findings confirm the involvement of α4β2 nAChR in 5IA85380-induced GABA release that seems to occur following membrane depolarization and opening calcium channels. CONCLUSIONS/SIGNIFICANCE: Rat hippocampal synaptosomes possess both α7 and α4β2 nAChR subtypes, which can modulate GABA release via two distinct mechanisms of action. The finding that GABA release evoked by the mixture of sub-maximal concentration of 5IA85380 plus sub-threshold concentrations of Ch was significantly larger than that elicited by the sum of the effects of the two agonists is compatible with the possibility that

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.

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 ...

Synthesis and release of fatty acids by human trophoblast cells in culture

International Nuclear Information System (INIS)

Coleman, R.A.; Haynes, E.B.

1987-01-01

In order to determine whether placental cells can synthesize and release fatty acids, trophoblast cells from term human placentas were established in monolayer culture. The cells continued to secrete placental lactogen and progesterone and maintained specific activities of critical enzymes of triacylglycerol and phosphatidylcholine biosynthesis for 24 to 72 hr in culture. Fatty acid was rapidly synthesized from [ 14 C]acetate and released by the cells. Palmitoleic, palmitic, and oleic acids were the major fatty acids synthesized from [ 14 C]acetate and released. Small amounts of lauric, myristic, and stearic acids were also identified. [ 14 C]acetate was also incorporated into cellular triacylglycerol, phospholipid, and cholesterol, but radiolabeled free fatty acid did not accumulate intracellularly. In a pulse-chase experiment, cellular glycerolipids were labeled with [1- 14 C]oleate; trophoblast cells then released 14 C-labeled fatty acid into the media as the cellular content of labeled phospholipid and triacylglycerol decreased without intracellular accumulation of free fatty acid. Twenty percent of the 14 C-label lost from cellular glycerolipid could not be recovered as a chloroform-extractable product, suggesting that some of the hydrolyzed fatty acid had been oxidized. These data indicate that cultured placenta trophoblast cells can release fatty acids that have either been synthesized de novo or that have been hydrolyzed from cellular glycerolipids. Trophoblast cells in monolayer culture should provide an excellent model for molecular studies of placental fatty acid metabolism and release

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

Science.gov (United States)

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

2009-01-01

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

Acetylcholine induces GABA release onto rod bipolar cells through heteromeric nicotinic receptors expressed in A17 amacrine cells.

Science.gov (United States)

Elgueta, Claudio; Vielma, Alex H; Palacios, Adrian G; Schmachtenberg, Oliver

2015-01-01

Acetylcholine (ACh) is a major retinal neurotransmitter that modulates visual processing through a large repertoire of cholinergic receptors expressed on different retinal cell types. ACh is released from starburst amacrine cells (SACs) under scotopic conditions, but its effects on cells of the rod pathway have not been investigated. Using whole-cell patch clamp recordings in slices of rat retina, we found that ACh application triggers GABA release onto rod bipolar (RB) cells. GABA was released from A17 amacrine cells and activated postsynaptic GABAA and GABAC receptors in RB cells. The sensitivity of ACh-induced currents to nicotinic ACh receptor (nAChR) antagonists (TMPH ~ mecamylamine > erysodine > DhβE > MLA) together with the differential potency of specific agonists to mimic ACh responses (cytisine > RJR2403 ~ choline), suggest that A17 cells express heteromeric nAChRs containing the β4 subunit. Activation of nAChRs induced GABA release after Ca(2+) accumulation in A17 cell dendrites and varicosities mediated by L-type voltage-gated calcium channels (VGCCs) and intracellular Ca(2+) stores. Inhibition of acetylcholinesterase depolarized A17 cells and increased spontaneous inhibitory postsynaptic currents in RB cells, indicating that endogenous ACh enhances GABAergic inhibition of RB cells. Moreover, injection of neostigmine or cytisine reduced the b-wave of the scotopic flash electroretinogram (ERG), suggesting that cholinergic modulation of GABA release controls RB cell activity in vivo. These results describe a novel regulatory mechanism of RB cell inhibition and complement our understanding of the neuromodulatory control of retinal signal processing.

A novel biodegradable nicotinic acid/calcium phosphate composite coating on Mg-3Zn alloy

Energy Technology Data Exchange (ETDEWEB)

Song, Yingwei, E-mail: ywsong@imr.ac.cn; Shan, Dayong; Han, En-Hou

2013-01-01

A novel biodegradable composite coating is prepared to reduce the biodegradation rate of Mg-3Zn alloy. The Mg-3Zn substrate is first immersed into 0.02 mol L{sup -1} nicotinic acid (NA) solution, named as vitamin B{sub 3}, to obtain a pretreatment film, and then the electrodeposition of calcium phosphate coating with ultrasonic agitation is carried out on the NA pretreatment film to obtain a NA/calcium phosphate composite coating. Surface morphology is observed by scanning electron microscopy (SEM). Chemical composition is determined by X-ray diffraction (XRD) and EDX. Protection property of the coatings is evaluated by electrochemical tests. The biodegradable behavior is investigated by immersion tests. The results indicate that a thin but compact bottom layer can be obtained by NA pretreatment. The electrodeposition calcium phosphate coating consists of many flake particles and ultrasonic agitation can greatly improve the compactness of the coating. The composite coating is biodegradable and can reduce the biodegradation rate of Mg alloys in stimulated body fluid (SBF) for twenty times. The biodegradation process of the composite coating can be attributed to the gradual dissolution of the flake particles into chippings. - Highlights: Black-Right-Pointing-Pointer NA/calcium phosphate composite coating is prepared to protect Mg-3Zn alloy implant. Black-Right-Pointing-Pointer Nicotinic acid (vitamin B{sub 3}) is available to obtain a protective bottom film. Black-Right-Pointing-Pointer Ultrasonic agitation greatly improves the compactness of calcium phosphate coating. Black-Right-Pointing-Pointer The composite coating can reduce the biodegradation rate of Mg-3Zn twenty times. Black-Right-Pointing-Pointer The composite coating is biodegraded by the dissolution of flakes into chippings.

Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

International Nuclear Information System (INIS)

Ma, Noelle; Nicholson, Catherine J.; Wong, Michael; Holloway, Alison C.; Hardy, Daniel B.

2014-01-01

While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

Energy Technology Data Exchange (ETDEWEB)

Ma, Noelle [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Nicholson, Catherine J. [Department of Obstetrics and Gynecology, McMaster University (Canada); Wong, Michael [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Holloway, Alison C. [Department of Obstetrics and Gynecology, McMaster University (Canada); Hardy, Daniel B., E-mail: Daniel.Hardy@schulich.uwo.ca [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Children' s Health Research Institute, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada)

2014-02-15

While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

Smoking-induced dopamine release studied with [11C]raclopride PET

International Nuclear Information System (INIS)

Kim, Yu Kyeong; Cho, Sang Soo; Lee, Do Hoon

2005-01-01

It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with and regulates the activation of the dopaminergic neuron. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [ 11 C]raclopride. Four male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.3±2.6 years) were enrolled in this study. Dopamine D2 receptor radioligand, [ 11 C]raclopride was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes (3x20s, 2x60s, 2x120s, 1x180s and 22x300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurements of plasma nicotine levels were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as striatal-cerebellar/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. The mean change in binding potential between the baseline and smoking in caudate, Putamen and ventral striatum was 3.7 % , 4.0 % and 8.6 %, respectively. This indicated the striatal dopamine release by smoking. The reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (r 2 =0.91, p=0.04). These data demonstrate that in vivo imaging with [ 11 C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking

E-Cigarette and Liquid Nicotine Exposures Among Young Children.

Science.gov (United States)

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

2018-04-23

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

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.

Chemical evolution. XXI - The amino acids released on hydrolysis of HCN oligomers

Science.gov (United States)

Ferris, J. P.; Wos, J. D.; Nooner, D. W.; Oro, J.

1974-01-01

Major amino acids released by hydrolysis of acidic and basic HCN oligomers are identified by chromatography as Gly, Asp, and diaminosuccinic acid. Smaller amounts of Ala, Ile and alpha-aminoisobutyric acid are also detected. The amino acids released did not change appreciably when the hydrolysis medium was changed from neutral to acidic or basic. The presence of both meso and d, l-diaminosuccinic acids was established by paper chromatography and on an amino acid analyzer.

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.

Intestinal release and uptake of phenolic antioxidant diferulic acids

DEFF Research Database (Denmark)

Andreasen, Mette Findal; Kroon, P A; Williamson, G

2001-01-01

Diferulic acids are potent antioxidants and are abundant structural components of plant cell walls, especially in cereal brans. As such, they are part of many human and animal diets and may contribute to the beneficial effect of cereal brans on health. However, these phenolics are ester-linked to......Diferulic acids are potent antioxidants and are abundant structural components of plant cell walls, especially in cereal brans. As such, they are part of many human and animal diets and may contribute to the beneficial effect of cereal brans on health. However, these phenolics are ester...... in oil. Our study also reveals that human and rat colonic microflora contain esterase activity able to release 5-5-, 8-O-4-, and 8-5-diferulic acids from model compounds and dietary cereal brans, hence providing a mechanism for release of dietary diferulates prior to absorption of the free acids....... In addition, cell-free extracts from human and rat small intestine mucosa exhibited esterase activity towards diferulate esters. Hence, we have shown that esterified diferulates can be released from cereal brans by intestinal enzymes, and that free diferulic acids can be absorbed and enter the circulatory...

Smoking-induced dopamine release studied with [{sup 11}C]raclopride PET

Energy Technology Data Exchange (ETDEWEB)

Kim, Yu Kyeong; Cho, Sang Soo; Lee, Do Hoon [Seoul National University College of Medicine, Seoul (Korea, Republic of)] (and others)

2005-07-01

It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with and regulates the activation of the dopaminergic neuron. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [{sup 11}C]raclopride. Four male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.3{+-}2.6 years) were enrolled in this study. Dopamine D2 receptor radioligand, [{sup 11}C]raclopride was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes (3x20s, 2x60s, 2x120s, 1x180s and 22x300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurements of plasma nicotine levels were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as striatal-cerebellar/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. The mean change in binding potential between the baseline and smoking in caudate, Putamen and ventral striatum was 3.7 % , 4.0 % and 8.6 %, respectively. This indicated the striatal dopamine release by smoking. The reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (r{sup 2}=0.91, p=0.04). These data demonstrate that in vivo imaging with [{sup 11}C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking.

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.

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.

The effect of ketamine on intraspinal acetylcholine release

DEFF Research Database (Denmark)

Abelson, Klas S P; Goldkuhl, Renée Röstlinger; Nylund, Anders

2006-01-01

The general anaesthetic ketamine affects the central cholinergic system in several manners, but its effect on spinal acetylcholine release, which may be an important transmitter in spinal antinociception, is unknown. This study aimed to investigate the effect of ketamine on spinal acetylcholine...... release. Microdialysis probes were placed intraspinally in male rats, and acetylcholine was quantified with HPLC. Anaesthesia was switched from isoflurane (1.3%) to ketamine (150 mg/kg h), which resulted in a 500% increased acetylcholine release. The increase was attenuated during nicotinic receptor...... blockade (50 microM mecamylamine). The nicotinic receptor agonist epibatidine (175 microM) produced a ten-fold higher relative increase of acetylcholine release during isoflurane anaesthesia compared to ketamine anaesthesia (270% to 27%). Intraspinal administration of ketamine and norketamine both...

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

Directory of Open Access Journals (Sweden)

Xiaoxiang Liao

2016-01-01

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

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.

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.

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

Science.gov (United States)

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

2009-03-01

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

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

Science.gov (United States)

D'Souza, Manoranjan S; Markou, Athina

2011-07-01

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

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

Digestion of thyroglobulin with purified thyroid lysosomes: preferential release of iodoamino acids

International Nuclear Information System (INIS)

Tokuyama, T.; Yoshinari, M.; Rawitch, A.B.; Taurog, A.

1987-01-01

[ 131 I]Thyroglobulin [( 131 I]Tg), prepared by either enzymatic iodination of human goiter Tg in vitro or isolation from the thyroids of rats previously injected with 131 I, was digested with a solubilized enzyme mixture prepared from purified hog thyroid lysosomes. The digestion was performed at 37 C for 24 h under nitrogen at pH 5.0 in the presence of 4 mM dithiothreitol. Under these conditions the release of free [ 131 I] iodoamino acids (MIT, DIT, T4, and T3) was quantitatively very similar to that observed with a standard pronase digestion procedure. To determine whether other amino acids in Tg were released as quantitatively as the iodoamino acids, free amino acids in the lysosomal digest were measured, and total free amino acid release was compared with a similar analysis performed after digestion of [ 131 I]Tg with 6 N HCl. Total amino acid release was much less complete than iodoamino acid release, indicating preferential release of iodoamino acids from Tg by lysosomal digestion. Analysis of the lysosomal digest by HPLC on a size exclusion column indicated that Tg was degraded to peptides with a mol wt less than 4000. Assuming that the in vitro lysosomal digestion system represents a valid model for the physiological proteolytic system that degrades Tg, the results of the present study suggest that a substantial portion of the Tg in the thyroid is not degraded to free amino acids and that peptide fragments of Tg are normally present in the thyroid. In such a case, the fate and possible physiological activity of these fragments require further elucidation

Nicotine inhibits collagen synthesis and alkaline phosphatase activity, but stimulates DNA synthesis in osteoblast-like cells

International Nuclear Information System (INIS)

Ramp, W.K.; Lenz, L.G.; Galvin, R.J.

1991-01-01

Use of smokeless tobacco is associated with various oral lesions including periodontal damage and alveolar bone loss. This study was performed to test the effects of nicotine on bone-forming cells at concentrations that occur in the saliva of smokeless tobacco users. Confluent cultures of osteoblast-like cells isolated from chick embryo calvariae were incubated for 2 days with nicotine added to the culture medium (25-600 micrograms/ml). Nicotine inhibited alkaline phosphatase in the cell layer and released to the medium, whereas glycolysis (as indexed by lactate production) was unaffected or slightly elevated. The effects on medium and cell layer alkaline phosphatase were concentration dependent with maximal inhibition occurring at 600 micrograms nicotine/ml. Nicotine essentially did not affect the noncollagenous protein content of the cell layer, but did inhibit collagen synthesis (hydroxylation of [ 3 H]proline and collagenase-digestible protein) at 100, 300, and 600 micrograms/ml. Release of [ 3 H]hydroxyproline to the medium was also decreased in a dose-dependent manner, as was the collagenase-digestible protein for both the medium and cell layer. In contrast, DNA synthesis (incorporation of [ 3 H]thymidine) was more than doubled by the alkaloid, whereas total DNA content was slightly inhibited at 600 micrograms/ml, suggesting stimulated cell turnover. Morphologic changes occurred in nicotine-treated cells including rounding up, detachment, and the occurrence of numerous large vacuoles. These results suggest that steps to reduce the salivary concentration of nicotine in smokeless tobacco users might diminish damaging effects of this product on alveolar bone

Development of a Controlled Release of Salicylic Acid Loaded Stearic Acid-Oleic Acid Nanoparticles in Cream for Topical Delivery

Directory of Open Access Journals (Sweden)

J. O. Woo

2014-01-01

Full Text Available Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release.

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

Science.gov (United States)

D'Souza, Manoranjan S

2016-01-01

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

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 (Vitam...

α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.

Directory of Open Access Journals (Sweden)

Tiina Maria Pirttimaki

Full Text Available It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism is through the release of gliotransmitters (GTs such as ATP, D-serine and most notably, glutamate, in response to astrocytic calcium elevations. We and others have shown that amyloid-β (Aβ, the toxic trigger for Alzheimer's disease (AD, interacts with hippocampal α7 nicotinic acetylcholine receptors (nAChRs. Since α7nAChRs are highly permeable to calcium and are expressed on hippocampal astrocytes, we investigated whether Aβ could activate astrocytic α7nAChRs in hippocampal slices and induce GT glutamate release. We found that biologically-relevant concentrations of Aβ1-42 elicited α7nAChR-dependent calcium elevations in hippocampal CA1 astrocytes and induced NMDAR-mediated slow inward currents (SICs in CA1 neurons. In the Tg2576 AD mouse model for Aβ over-production and accumulation, we found that spontaneous astrocytic calcium elevations were of higher frequency compared to wildtype (WT. The frequency and kinetic parameters of AD mice SICs indicated enhanced gliotransmission, possibly due to increased endogenous Aβ observed in this model. Activation of α7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal neurons while α7nAChRs on astrocytes of AD mice were abrogated. These findings suggest that, at an age that far precedes the emergence of cognitive deficits and plaque deposition, this mouse model for AD-like amyloidosis exhibits augmented astrocytic activity and glutamate GT release suggesting possible repercussions for preclinical AD hippocampal neural networks that contribute to subsequent cognitive decline.

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 ...

Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

International Nuclear Information System (INIS)

Qiao, Dan; Seidler, Frederic J.; Slotkin, Theodore A.

2005-01-01

Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E. Initiating differentiation with nerve growth factor, which enhances nicotinic acetylcholine receptor expression, increased the TBARS response to nicotine but not chlorpyrifos, suggesting that the two agents act by different originating mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine protected the cells from oxidative damage evoked by chlorpyrifos and similarly blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with nicotine elicited increases in TBARS in multiple brain regions when given in doses that simulate plasma nicotine concentrations found in smokers or at one-tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit oxidative damage to developing neural cells both in vitro and in vivo, a mechanism that explains some of the neurodevelopmental endpoints that are common to the two agents. The balance between neuroprotectant and neurotoxicant actions of nicotine may be particularly important in situations where exposure to tobacco smoke is combined with other prooxidant insults

Combined α7 nicotinic acetylcholine receptor agonism and partial serotonin transporter inhibition produce antidepressant-like effects in the mouse forced swim and tail suspension tests

DEFF Research Database (Denmark)

Andreasen, Jesper T; Redrobe, John P; Nielsen, Elsebet Ø

2012-01-01

Emerging evidence points to an involvement of nicotinic acetylcholine receptors (nAChRs) in major depression. Nicotine improves symptoms of depression in humans and shows antidepressant-like effects in rodents. Monoamine release is facilitated by nAChR stimulation, and nicotine-evoked serotonin (5...

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

Science.gov (United States)

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

2009-02-01

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

Numerical simulation of the effects of dilution level, depth of inhalation, and smoke composition on nicotine vapor deposition during cigarette smoking.

Science.gov (United States)

Ingebrethsen, Bradley J

2006-12-01

A numerical model of an aerosol containing vaporizable nicotine depositing to the walls of a tube was developed and applied to simulate the vapor deposition of nicotine in a denuder tube and under conditions approximating those in the respiratory tract during mainstream cigarette smoke inhalation. The numerical model was validated by comparison to data for denuder tube collection of nicotine from the smoke of three types of cigarette differing in smoke acidity and nicotine volatility. Simulations predict that the absorption of water by aerosol particles inhibits nicotine vapor deposition to tube walls, and that increased temperature, decreased tube diameter, and increased dilution enhance nicotine vapor deposition rate. The combined effect of changing these four parameters to approximate the transition from conducting to gas exchange regions of the respiratory tract was a significant net increase in predicted nicotine vapor deposition rate. Comparisons of nicotine deposition rates between conditions in the conducting airways and those in the gas exchange region were informative with regard to reported nicotine retention measurements during human smoking. Reports that vaporizable nicotine can penetrate past the conducting airways, that nicotine can be retained at near 100% efficiency from mainstream smoke, and that cigarettes with differing acidity and nicotine volatility have similar nicotine uptake rates are all shown to be consistent with the results of the model simulations.

Blockade of nicotine sensitization by methanol extracts of Glycyrrhizae radix mediated via antagonism of accumbal oxidative stress.

Science.gov (United States)

Zhao, Zheng Lin; Kim, Sang Chan; Liu, Hong Feng; Wu, Yi Yan; Li, Li Bo; Wang, Yu Hua; Jiao, Yu; Fan, Yu; Lee, Chul Won; Lee, Bong Hyeo; Cho, Il Je; Yang, Chae Ha; Zhao, Rong Jie

2017-11-16

We previously reported that a methanol extract of Glycyrrhizae radix (MEGR) blocked methamphetamine-induced locomotor sensitization and conditioned place preference in rats. In the present study, the effects of MEGR on repeated nicotine-induced locomotor sensitization and enhanced extracellular dopamine (DA) release in the nucleus accumbens (Nacc) were evaluated. Male Sprague-Dawley rats received repeated administrations of nicotine (0.4 mg/kg, subcutaneous) or saline twice a day for 7 d and were challenged with nicotine 4 d after the last daily dosing. During the 4-d withdrawal period, the rats were treated once a day with MEGR (60 or 180 mg/kg/d). Extracellular DA levels were measured by in vivo microdialysis, the malondialdehyde levels and the activities of superoxide dismutase and catalase in the Nacc were biochemically evaluated, and the expression of antioxidant proteins was confirmed by Western blot assays. All data were assessed with analysis of variance tests followed by post-hoc comparison tests and p values nicotine-induced locomotor sensitization was dose-dependently attenuated by MEGR, and 180 mg/kg/d MEGR significantly inhibited augmented accumbal DA release induced by a direct local challenge of nicotine. Moreover, 180 mg/kg/d MEGR reversed increases in malondialdehyde production, decreases in superoxide dismutase and catalase activities, and the reduced expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1 in the nicotine-sensitized Nacc. These results suggest that MEGR inhibited nicotine-induced locomotion and dopaminergic sensitization via antioxidant action.

Smoking-induced dopamine release studied with [{sup 11}C]Raclopride PET

Energy Technology Data Exchange (ETDEWEB)

Kim, Yu Kyeong; Cho, Sang Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Do Hoon [Center for Clinical Services, National Cancer Certer, Goyang (Korea, Republic of)] (and others)

2005-10-15

It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [{sup 11}C]raclopride. Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.4 {+-} 1.7 years) were enrolled in this study. [{sup 1C}]raclopride, a dopamine D2 receptor radioligand, was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes (3 x 20s, 2 x 60s, 2 x 120s, 1 x 180s and 22 x 300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar)/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. The mean decrease in binding potential of [{sup 1C}]raclopride between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7%, 4.0% and 7.8%, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, {rho} =0.4). These data demonstrate that in vivo imaging with [{sup 11}C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking.

Effect of the MK 801 and (-) nicotine intracerebral administration on Glu and Gaba extracellular concentration in the pedunculopontine nucleus from rats

International Nuclear Information System (INIS)

Blanco Lezcano, Lisette; Lorigados Pedre, Lourdes del Carmen; Gonzalez Fraguela, Maria Elena and others

2011-01-01

Although the pharmacological manipulation of the glutamatergic and cholinergic systems have been studied in animal models of Parkinson's Disease (PD), only some authors have done work on this topic at the pedunculopontine nucleus (PPN). The present work studied the changes in glutamate (Glu) and δ-aminobutyric acid (GABA) extracellular concentrations (EC) in the PPN from hemiparkinsonian rats by 6hydroxydopamine injection. The rats were locally perfused by MK-801 (10 μ mol/l) or (-) nicotine (10 mm) solutions by cerebral microdialysis. The biochemical studies were carried out through high performance liquid chromatography coupled to fluorescence detection. Mk-801 infusion induced a significant decrease of Glu (p< 0.01) and GABA (p< 0.01) EC in PPN. On the other hand (-) nicotine infusion induced a significant increase of Glu (p< 0.001) and GABA (p< 0.001) EC in PPN from hemiparkinsonian rats. The local blockade of NMDA receptors by MK-801 infusion facilitates the interaction between Glu and their metabotropic receptors that take part in presynaptic inhibition mechanisms and interfere with neurotransmitters release. Meanwhile, the nicotine infusion sums the effects of nicotinic receptor activation with the glutamatergic and gabaergic neurotransmission changes produced in the PPN in the parkinsonian condition. The cholinergic and glutamergic drug infusion in PPN impose a new adjustment to the neurotransmission at this level that is added to the neurochemical changes associated to dopaminergic denervation.

Acute effects of nicotine and smoking on blood flow, tissue oxygen, and aerobe metabolism of the skin and subcutis

DEFF Research Database (Denmark)

Sørensen, Lars Tue; Jørgensen, Stig; Petersen, Lars J

2009-01-01

BACKGROUND: Nicotine released from tobacco smoke causing reduction in blood flow has been suggested as causative for postoperative wound complications in smokers, but the mechanism remains unknown. MATERIALS AND METHODS: In eight healthy male smokers and eight ex-smokers, the cutaneous and subcut......BACKGROUND: Nicotine released from tobacco smoke causing reduction in blood flow has been suggested as causative for postoperative wound complications in smokers, but the mechanism remains unknown. MATERIALS AND METHODS: In eight healthy male smokers and eight ex-smokers, the cutaneous...... and subcutaneous blood flow (QBF, SqBF) was assessed by Laser Doppler and 133Xe clearance. Tissue oxygen tension (TO(2)) was measured by a LICOX O(2)-electrode. Tissue glucose and lactate (Tgluc, Tlact) were assessed by microdialysis. The parameters were studied after intravenous infusion of 1.0 mg nicotine......, smoking of one cigarette, arterial occlusion, and reperfusion. RESULTS: Nicotine infusion decreased SqBF from 4.2 +/- 2.0 to 3.1 +/- 1.2 mL/100 g tissue/min (P

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

Science.gov (United States)

Ye, Yangfang; Wang, Xin; Zhang, Limin; Lu, Zhenmei; Yan, Xiaojun

2012-07-01

Nicotine can cause oxidative damage to organisms; however, some bacteria, for example Pseudomonas sp. HF-1, are resistant to such oxidative stress. In the present study, we analyzed the concentration-dependent metabolic response of Pseudomonas sp. HF-1 to nicotine stress using ¹H NMR spectroscopy coupled with multivariate data analysis. We found that the dominant metabolites in Pseudomonas sp. HF-1 were eight aliphatic organic acids, six amino acids, three sugars and 11 nucleotides. After 18 h of cultivation, 1 g/L nicotine caused significant elevation of sugar (glucose, trehalose and maltose), succinate and nucleic acid metabolites (cytidine, 5'-CMP, guanine 2',3'-cyclic phosphate and adenosine 2',3'-cyclic phosphate), but decrease of glutamate, putrescine, pyrimidine, 2-propanol, diethyl ether and acetamide levels. Similar metabolomic changes were induced by 2 g/L nicotine, except that no significant change in trehalose, 5'-UMP levels and diethyl ether were found. However, 3 g/L nicotine led to a significant elevation in the two sugars (trehalose and maltose) levels and decrease in the levels of glutamate, putrescine, pyrimidine and 2-propanol. Our findings indicated that nicotine resulted in the enhanced nucleotide biosynthesis, decreased glucose catabolism, elevated succinate accumulation, severe disturbance in osmoregulation and complex antioxidant strategy. And a further increase of nicotine level was a critical threshold value that triggered the change of metabolic flow in Pseudomonas sp. HF-1. These findings revealed the comprehensive insights into the metabolic response of nicotine-degrading bacteria to nicotine-induced oxidative toxicity.

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.

Phosphorus release from phosphate rock and iron phosphate by low-molecular-weight organic acids.

Science.gov (United States)

Xu, Ren-kou; Zhu, Yong-guan; Chittleborough, David

2004-01-01

Low-molecular-weight(LMW) organic acids widely exist in soils, particularly in the rhizosphere. A series of batch experiments were carried out to investigate the phosphorus release from rock phosphate and iron phosphate by low-molecular-weight organic acids. Results showed that citric acid had the highest capacity to solubilize P from both rock and iron phosphate. P solubilization from rock phosphate and iron phosphate resulted in net proton consumption. P release from rock phosphate was positively correlated with the pKa values. P release from iron phosphate was positively correlated with Fe-organic acid stability constants except for aromatic acids, but was notcorrelated with pKa. Increase in the concentrations of organic acids enhanced P solubilization from both rock and iron phosphate almost linearly. Addition of phenolic compounds further increased the P release from iron phosphate. Initial solution pH had much more substantial effect on P release from rock phosphate than from iron phosphate.

Adsorption and release of ofloxacin from acid- and heat-treated halloysite.

Science.gov (United States)

Wang, Qin; Zhang, Junping; Zheng, Yue; Wang, Aiqin

2014-01-01

Halloysite nanotube is an ideal vehicle of the controlled release of drugs. In this study, we systematically investigated the effects of acid- and heat-treatments on the physicochemical properties, structure and morphology of halloysite by XRD, FTIR, SEM and TEM. Afterwards, the adsorption and in vitro release properties of halloysite for cationic ofloxacin (OFL) were evaluated. The results indicate that HCl treatment has no influence on the crystal structure of halloysite, whereas it becomes amorphous after calcined at temperature higher than 500 °C. Both acid- and heat-treatments have no evident influence on the tubular structure of halloysite. OFL was adsorbed onto halloysite via electrostatic interaction between protonated OFL and negative halloysite surface, cation exchange as well as electrostatic interaction between the OFL-Al(3+) complexes and the negative halloysite surface. Acid-treatment facilitates the release of the adsorbed OFL compared with the natural halloysite in spite of a slight decrease of adsorption capacity. However, heat-treatment results in a sharp decrease of adsorption capacity for OFL owning to the OFL-promoted dissolution of aluminum and the disappearance of the porous structure. Although heat-treatment also facilitates release of the adsorbed OFL, the amount of OFL released is in fact less than the natural halloysite owing to the very low adsorption capacity. Thus, acid-activation is an effective protocol to improve the adsorption and release of halloysite for cationic drug molecules. Copyright © 2013 Elsevier B.V. All rights reserved.

Hydrothermal synthesis and processing of hydrogen titanate nanotubes for nicotine electrochemical sensing

Science.gov (United States)

Mersal, Gaber A. M.; Mostafa, Nasser Y.; Omar, Abd-Elkader H.

2017-08-01

Hydrogen titanate nanotubes (HTNT) were prepared via acid washing of hydrothermally synthesized sodium titantate nanotube. HTNTs with diameters in the range 7-9 nm and length of several hundred nanometers were annealed at different temperatures and used to modify carbon paste electrode (CPE). Cyclic and square wave voltammetric techniques were used to investigate the behavior of nicotine at HTNT modified carbon paste electrode (HTNTCPE). The nicotine-oxidation reaction over HTNTCPE was irreversible and adsorption process is the rate determining step. HTNTs annealed at 500 °C showed the best response to nicotine. The nicotine concentration was determined at the ideal conditions by square wave voltammetry (SWV). The calibration was linear from 0.1 to 500.0 µmol l-1 with a correlation coefficient of 0.995. The detection limits were found to be 0.005 µmol l-1. The present HTNTCPE was used to the determination of nicotine in two cigarette brands and it showed outstanding performance with respect to detection limit and sensitivity.

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.

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...

Controlled Pesticide Release from Porous Composite Hydrogels Based on Lignin and Polyacrylic Acid

Directory of Open Access Journals (Sweden)

Yajie Sun

2016-01-01

Full Text Available For the controlled release of pesticides, a novel composite porous hydrogel (LBPAA was prepared based on lignin and polyacrylic acid for use as the support frame of a pore structure for water delivery. The LBPAA was analyzed to determine its water-swelling and slow release properties. The controlled release properties of LBPAA were evaluated through experiments in relation to the cumulative release of pesticides, with particular emphasis on environmental effects and release models. The porous LBPAA hydrogel showed improved properties compared to polyacrylic acid, and could therefore be considered an efficient material for application in controlled release systems in agriculture.

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

Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy

Directory of Open Access Journals (Sweden)

Jurkić Lela Munjas

2013-01-01

Full Text Available Abstract Silicon (Si is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4, as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K, the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel, silica gel (amorphous silicon dioxide, and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4 in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources.

Inhibition of monoacylglycerol lipase (MAGL) enhances cue-induced reinstatement of nicotine-seeking behavior in mice.

Science.gov (United States)

Trigo, Jose M; Le Foll, Bernard

2016-05-01

Tobacco smoking is still a major population health issue. The endocannabinoid system has been shown to control drug-seeking behaviors. There are two main endocannabinoids: anandamide degraded by fatty acid amide hydrolase (FAAH) and 2-arachidonoylglycerol (2-AG) degraded by monoacylglycerol lipase (MAGL). The role of MAGL has only been explored recently, and so far, no study have been performed to evaluate the effects of MAGL inhibitor on nicotine reinforcing properties and cue-induced reinstatement of nicotine seeking. Here, we investigated the effects of the MAGL inhibitor JZL184 on nicotine self-administration under fixed and progressive-ratio schedules of reinforcement and on cue-induced reinstatement of nicotine seeking in mice. We also evaluated the effects of JZL184 on food self-administration for possible non-specific effects. JZL184 (0, 8, and 16 mg/kg) did not affect food taking, nicotine taking, or motivation for nicotine. MAGL inhibition by JZL184 (16 mg/kg) increased reinstatement of previously extinguished nicotine seeking induced by presentation of nicotine-associated cues, but did not produce reinstatement on its own. This study implicates involvement of 2-AG in nicotine-seeking behaviors.

Enduring effects of perinatal nicotine exposure on murine sleep in adulthood.

Science.gov (United States)

Borniger, Jeremy C; Don, Reuben F; Zhang, Ning; Boyd, R Thomas; Nelson, Randy J

2017-09-01

The long-term consequences of early life nicotine exposure are poorly defined. Approximately 8-10% of women report smoking during pregnancy, and this may promote aberrant development in the offspring. To this end, we investigated potential enduring effects of perinatal nicotine exposure on murine sleep and affective behaviors in adulthood (~13-15 wk of age) in C57Bl6j mice. Mothers received a water bottle containing 200 µg/ml nicotine bitartrate dihydrate in 2% wt/vol saccharin or pH-matched 2% saccharin with 0.2% (vol/vol) tartaric acid throughout pregnancy and before weaning. Upon reaching adulthood, offspring were tested in the open field and elevated plus maze, as well as the forced swim and sucrose anhedonia tests. Nicotine-exposed male (but not female) mice had reduced mobility in the open field, but no differences were observed in anxiety-like or depressive-like responses. Upon observing this male-specific phenotype, we further assessed sleep-wake states via wireless EEG/EMG telemetry. Following baseline recording, we assessed whether mice exposed to nicotine altered their homeostatic response to 5 h of total sleep deprivation and whether nicotine influenced responses to a powerful somnogen [i.e., lipopolysaccharides (LPS)]. Males exposed to perinatal nicotine decreased the percent time spent awake and increased time in non-rapid eye movement (NREM) sleep, without changes to REM sleep. Nicotine-exposed males also displayed exaggerated responses (increased time asleep and NREM spectral power) to sleep deprivation. Nicotine-exposed animals additionally had blunted EEG slow-wave responses to LPS administration. Together, our data suggest that perinatal nicotine exposure has long-lasting effects on normal sleep and homeostatic sleep processes into adulthood. Copyright © 2017 the American Physiological Society.

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...

Characterization of unsaturated fatty acid sustained-release microspheres for long-term algal inhibition.

Science.gov (United States)

Ni, Lixiao; Jie, Xiaoting; Wang, Peifang; Li, Shiyin; Hu, Shuzhen; Li, Yiping; Li, Yong; Acharya, Kumud

2015-02-01

The unsaturated fatty acid (linoleic acid) sustained-release microspheres were prepared with linoleic acid (LA) using alginate-chitosan microcapsule technology. These LA sustained-release microspheres had a high encapsulation efficiency (up to 62%) tested by high performance liquid chromatography with a photo diode array. The dry microspheres were characterized by a scanning electron microscope, X-ray diffraction measurement, dynamic thermogravimetric analysis and Fourier transform infrared spectral analysis. The results of characterization showed that the microspheres had good thermal stability (decomposition temperature of 236°C), stable and temperature independent release properties (release time of more than 40 d). Compared to direct dosing of LA, LA sustained-released microspheres could inhibit Microcystis aeruginosa growth to the non-growth state. The results of this study suggested that the LA sustained-release microspheres may be a potential candidate for algal inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Depolarization-induced release of amino acids from the vestibular nuclear complex.

Science.gov (United States)

Godfrey, Donald A; Sun, Yizhe; Frisch, Christopher; Godfrey, Matthew A; Rubin, Allan M

2012-04-01

There is evidence from immunohistochemistry, quantitative microchemistry, and pharmacology for several amino acids as neurotransmitters in the vestibular nuclear complex (VNC), including glutamate, γ-aminobutyrate (GABA), and glycine. However, evidence from measurements of release has been limited. The purpose of this study was to measure depolarization-stimulated calcium-dependent release of amino acids from the VNC in brain slices. Coronal slices containing predominantly the VNC were prepared from rats and perfused with artificial cerebrospinal fluid (ACSF) in an interface chamber. Fluid was collected from the chamber just downstream from the VNC using a microsiphon. Depolarization was induced by 50 mM potassium in either control calcium and magnesium concentrations or reduced calcium and elevated magnesium. Amino acid concentrations in effluent fluid were measured by high performance liquid chromatography. Glutamate release increased fivefold during depolarization in control calcium concentration and twofold in low calcium/high magnesium. These same ratios were 6 and 1.5 for GABA, 2 and 1.3 for glycine, and 2 and 1.5 for aspartate. Differences between release in control and low calcium/high magnesium ACSF were statistically significant for glutamate, GABA, and glycine. Glutamine release decreased during and after depolarization, and taurine release slowly increased. No evidence for calcium-dependent release was found for serine, glutamine, alanine, threonine, arginine, taurine, or tyrosine. Our results support glutamate and GABA as major neurotransmitters in the VNC. They also support glycine as a neurotransmitter and some function for taurine.

Synthesis, characterization, and thermochemistry of the solid state coordination compound Zn(Nic){sub 2} . H{sub 2}O(s) (Nic = nicotinic acid)

Energy Technology Data Exchange (ETDEWEB)

Di Youying [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong (China)], E-mail: yydi@lcu.edu.cn; Hong Yuanping; Kong Yuxia; Yang Weiwei [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong (China); Tan Zhicheng [Thermochemistry Laboratory, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China)

2009-01-15

A novel compound, viz. zinc nicotinate monohydrate, was synthesized by the method of room temperature solid phase synthesis. The techniques of FT-IR chemical and elemental analyses and X-ray powder diffraction were applied to characterise the structure and composition of the complex. In accordance with Hess' law, a thermochemical cycle was designed and the enthalpy change of the solid phase reaction of nicotinic acid with hydrated zinc acetate was determined to be {delta}{sub r}H{sub m}{sup 0}=(46.71{+-}0.21)kJ.mol{sup -1} by use of an isoperibol solution-reaction calorimeter. The standard molar enthalpy of formation of the title complex Zn(Nic){sub 2} . H{sub 2}O(s) was calculated as -(1062.3 {+-} 2.0) kJ . mol{sup -1} by use of the enthalpies of dissolution and other auxiliary thermodynamic data.

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

Influence of labelling with radiohalogens in 2-sup(18)F-,6-sup(18)F- and 6-sup(123)I-nicotinic acid diethylamide on biodistribution in mice

International Nuclear Information System (INIS)

Knust, E.J.; Machulla, H.-J.; Kafka, Ch.

1985-01-01

By comparison of three halogenated nicotinic acid derivatives, viz. 2-sup(18)F-, 6-sup(18)F- and 6-sup(123)I-nicotinic acid diethylamide (2-sup(18)F-NADA, 6-sup(18)F-NADA, 6-sup(123)I-NADA), the biodistribution of sup(18)F- and sup(123)I-radioactivity in mice was determined. For the two fluoro-compounds the results indicate nearly similar time-activity curves in almost all organs investigated, while the iodo-derivative exhibits significant differences: for the brain and the heart a complete elimination of sup(123)I-radioactivity takes place within 4 hours, time-activity curves of the liver and the kidneys show higher maximal accumulation compared to the fluorinated derivatives and activity in the stomach increases continuously. For the lung drastic differences can also be observed. De-fluorination reactions from the aromatic ring can be excluded as could be shown by the low accumulation of sup(18)F-radioactivity in bones after application of 6-sup(18)F-NADA. (author)

pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids

Directory of Open Access Journals (Sweden)

2008-08-01

Full Text Available Background and purpose of the study: Propranolol HCl, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Methods: Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15 % were added to the matrices prepared by hydroxypropyl methylcellulose (HPMC and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time (MDT as well as similarity factor (¦2 were calculated for all formulations. Results and discussion: It was found that incorporation of 5 and 10 % tartaric acid in tablet formulations with 30 % HPMC resulted in a suitable pH-independent release profiles with significant higher ¦2 values (89.9 and 87.6 respectively compared to acid free tablet (58.03. The other two acids did not show the desirable effects. It seems that lower pKa of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles.

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.

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.

Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand.

Science.gov (United States)

Watson, Brittany M; Oliveria, John Paul; Nusca, Graeme M; Smith, Steven G; Beaudin, Sue; Dua, Benny; Watson, Rick M; Assayag, Evelynne Israël; Cormier, Yvon F; Sehmi, Roma; Gauvreau, Gail M

2014-01-01

Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet. We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic ligand, on in vitro anti-IgE and in vivo allergen-induced basophil activation. Basophils were enriched from the peripheral blood of allergic donors and the expression of nAChR subunits and muscarinic receptors was determined. Purified basophils were stimulated with anti-IgE in the presence of ASM-024 with or without muscarinic or nicotinic antagonists for the measurement of CD203c expression and histamine release. The effect of 9 days of treatment with 50 and 200 mg ASM-024 on basophil CD203c expression was examined in the blood of mild allergic asthmatics before and after allergen inhalation challenge. nAChR α4, α7 and α1/α3/α5 receptor subunit expression was detected on basophils. Stimulation of basophils with anti-IgE increased CD203c expression and histamine release, which was inhibited by ASM-024 (10(-5) to 10(-)(3) M, p ASM-024 was reversed in the presence of muscarinic and nicotinic antagonists. In subjects with mild asthma, ASM-024 inhalation significantly inhibited basophil CD203c expression measured 24 h after allergen challenge (p = 0.03). This study shows that ASM-024 inhibits IgE- and allergen-induced basophil activation through both nicotinic and muscarinic receptors, and suggests that ASM-024 may be an efficacious agent for modulating allergic asthma responses. © 2015 S. Karger AG, Basel.

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

Science.gov (United States)

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

2010-09-01

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

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

Amino Acid Transporters and Release of Hydrophobic Amino Acids in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120

Directory of Open Access Journals (Sweden)

Rafael Pernil

2015-04-01

Full Text Available Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that can use inorganic compounds such as nitrate or ammonium as nitrogen sources. In the absence of combined nitrogen, it can fix N2 in differentiated cells called heterocysts. Anabaena also shows substantial activities of amino acid uptake, and three ABC-type transporters for amino acids have been previously characterized. Seven new loci encoding predicted amino acid transporters were identified in the Anabaena genomic sequence and inactivated. Two of them were involved in amino acid uptake. Locus alr2535-alr2541 encodes the elements of a hydrophobic amino acid ABC-type transporter that is mainly involved in the uptake of glycine. ORF all0342 encodes a putative transporter from the dicarboxylate/amino acid:cation symporter (DAACS family whose inactivation resulted in an increased uptake of a broad range of amino acids. An assay to study amino acid release from Anabaena filaments to the external medium was set up. Net release of the alanine analogue α-aminoisobutyric acid (AIB was observed when transport system N-I (a hydrophobic amino acid ABC-type transporter was engaged in the uptake of a specific substrate. The rate of AIB release was directly proportional to the intracellular AIB concentration, suggesting leakage from the cells by diffusion.

Acid-Labile Acyclic Cucurbit[n]uril Molecular Containers for Controlled Release.

Science.gov (United States)

Mao, Dake; Liang, Yajun; Liu, Yamin; Zhou, Xianhao; Ma, Jiaqi; Jiang, Biao; Liu, Jia; Ma, Da

2017-10-02

Stimuli-responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. A new type of acid labile acyclic cucurbit[n]uril (CB[n]) molecular containers is presented that can degrade and release the encapsulated cargo at accelerated rates under mildly acidic conditions (pH 5.5-6.5). These containers retain the excellent recognition properties of CB[n]-type hosts. A cell culture study demonstrated that the cellular uptake of cargos could be fine-tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigating the role of ion-pair strategy in regulating nicotine release from patch: Mechanistic insights based on intermolecular interaction and mobility of pressure sensitive adhesive.

Science.gov (United States)

Li, Qiaoyun; Wan, Xiaocao; Liu, Chao; Fang, Liang

2018-07-01

The aim of this study was to prepare a drug-in-adhesive patch of nicotine (NIC) and use ion-pair strategy to regulate drug delivery rate. Moreover, the mechanism of how ion-pair strategy regulated drug release was elucidated at molecular level. Formulation factors including pressure sensitive adhesives (PSAs), drug loading and counter ions (C 4 , C 6 , C 8 , C 10 , and C 12 ) were screened. In vitro release experiment and in vitro transdermal experiment were conducted to determine the rate-limiting step in drug delivery process. FT-IR and molecular modeling were used to characterize the interaction between drug and PSA. Thermal analysis and rheology study were conducted to investigate the mobility variation of PSA. The optimized patch prepared with NIC-C 8 had the transdermal profile fairly close to that of the commercial product (p > 0.05). The release rate constants (k) of NIC, NIC-C 4 and NIC-C 10 were 21.1, 14.4 and 32.4, respectively. Different release rates of NIC ion-pair complexes were attributed to the dual effect of ion-pair strategy on drug release. On one hand, ion-pair strategy enhanced the interaction between drug and PSA, which inhibited drug release. On the other hand, using ion-pair strategy improved the mobility of PSA, which facilitated drug release. Drug release behavior was determined by combined effect of two aspects above. These conclusions provided a new idea for us to regulate drug release behavior from patch. Copyright © 2018 Elsevier B.V. All rights reserved.

Isotopic rubidium ion efflux assay for the functional characterization of nicotinic acetylcholine receptors on clonal cell lines

International Nuclear Information System (INIS)

Lukas, R.J.; Cullen, M.J.

1988-01-01

An isotopic rubidium ion efflux assay has been developed for the functional characterization of nicotinic acetylcholine receptors on cultured neurons. This assay first involves the intracellular sequestration of isotopic potassium ion analog by the ouabain-sensitive action of a sodium-potassium ATPase. Subsequently, the release of isotopic rubidium ion through nicotinic acetylcholine receptor-coupled monovalent cation channels is activated by application of nicotinic agonists. Specificity of receptor-mediated efflux is demonstrated by its sensitivity to blockade by nicotinic, but not muscarinic, antagonists. The time course of agonist-mediated efflux, within the temporal limitations of the assay, indicates a slow inactivation of receptor function on prolonged exposure to agonist. Dose-response profiles (i) have characteristic shapes for different nicotinic agonists, (ii) are described by three operationally defined parameters, and (iii) reflect different affinities of agonists for binding sites that control receptor activation and functional inhibition. The rubidium ion efflux assay provides fewer hazards but greater sensitivity and resolution than isotopic sodium or rubidium ion influx assays for functional nicotinic receptors

Effects of Prepartum Dietary Energy Level and Nicotinic Acid Supplementation on Immunological, Hematological and Biochemical Parameters of Periparturient Dairy Cows Differing in Parity

Science.gov (United States)

Tienken, Reka; Kersten, Susanne; Frahm, Jana; Hüther, Liane; Meyer, Ulrich; Huber, Korinna; Rehage, Jürgen; Dänicke, Sven

2015-01-01

Simple Summary Several biological changes occur during the transition from late pregnancy to early lactation which is associated with a high susceptibility of health disorders. Nicotinic acid, as feed additive, is suggested to balance catabolic metabolism of periparturient dairy cows by attenuating lipolysis and impact production performance. This study provides information of the biological changes occurring around parturition with special emphasis on differences between primiparous and multiparous cows. Present results showed that energy-dense feeding prepartum did not result in metabolic imbalances postpartum in dairy cows which were similar in body condition score. Nicotinic acid supplementation did not reveal any effect. Abstract The periparturient period is critical according to health, productivity and profitability. As this period is fundamental for the success of the lactation period, the interest in improving periparturient health by dietary supplements increased in recent years. The present study investigated the effects of feeding nicotinic acid (NA) combined with varying dietary energy densities on immunological, hematological and biochemical parameters of periparturient cows differing in parity. Thirty-six multiparous and 20 primiparous dairy cows were enrolled in the study 42 days before expected parturition date until 100 days postpartum with the half of the cows being supplemented with 24 g of NA/d. After parturition a diet with 30% concentrate was fed to all cows which was followed by different concentrate escalation strategies. Dietary NA supplementation was ceased on day 24 postpartum. Dietary NA increased (P = 0.010) serum nicotinamide concentrations (mean of 3.35 ± 1.65 µg/mL), whereas NA could not be detected. Present data emphasize that periparturient cows are faced with major physiological challenges and that both parity-groups have different prerequisites to adapt to those changes irrespective of NA supplementation. The overfeeding of

The preparation and the sustained release of titanium dioxide hollow particles encapsulating L-ascorbic acid

Science.gov (United States)

Tominaga, Yoko; Kadota, Kazunori; Shimosaka, Atsuko; Yoshida, Mikio; Oshima, Kotaro; Shirakawa, Yoshiyuki

2018-05-01

The preparation of the titanium dioxide hollow particles encapsulating L-ascorbic acid via sol-gel process using inkjet nozzle has been performed, and the sustained release and the effect protecting against degradation of L-ascorbic acid in the particles were investigated. The morphology of titanium dioxide particles was evaluated by scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS). The sustained release and the effect protecting against degradation of L-ascorbic acid were estimated by dialysis bag method in phosphate buffer saline (PBS) (pH = 7.4) as release media. The prepared titanium dioxide particles exhibited spherical porous structures. The particle size distribution of the titanium dioxide particles was uniform. The hollow titanium dioxide particles encapsulating L-ascorbic acid showed the sustained release. It was also found that the degradation of L-ascorbic acid could be inhibited by encapsulating L-ascorbic acid in the titanium dioxide hollow particles.

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.

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

Antimony leaching release from brake pads: Effect of pH, temperature and organic acids.

Science.gov (United States)

Hu, Xingyun; He, Mengchang; Li, Sisi

2015-03-01

Metals from automotive brake pads pollute water, soils and the ambient air. The environmental effect on water of antimony (Sb) contained in brake pads has been largely untested. The content of Sb in one abandoned brake pad reached up to 1.62×10(4) mg/kg. Effects of initial pH, temperature and four organic acids (acetic acid, oxalic acid, citric acid and humic acid) on Sb release from brake pads were studied using batch reactors. Approximately 30% (97 mg/L) of the total Sb contained in the brake pads was released in alkaline aqueous solution and at higher temperature after 30 days of leaching. The organic acids tested restrained Sb release, especially acetic acid and oxalic acid. The pH-dependent concentration change of Sb in aqueous solution was best fitted by a logarithmic function. In addition, Sb contained in topsoil from land where brake pads were discarded (average 9×10(3) mg/kg) was 3000 times that in uncontaminated soils (2.7±1 mg/kg) in the same areas. Because potentially high amounts of Sb may be released from brake pads, it is important that producers and environmental authorities take precautions. Copyright © 2015. Published by Elsevier B.V.

Growth and characterization of nonlinear optical single crystal: Nicotinic L-tartaric

Energy Technology Data Exchange (ETDEWEB)

Sheelarani, V.; Shanthi, J., E-mail: shanthinelson@gmail.com [Department of Physics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore-641043 (India)

2015-06-24

Nonlinear optical single crystals were grown from Nicotinic and L-Tartaric acid by slow evaporation technique at room temperature. Structure of the grown crystal was confirmed by single crystal X-ray diffraction studies, The crystallinity of the Nicotinic L-Tartaric (NLT) crystals was confirmed from the powder XRD pattern. The transparent range and cut off wavelength of the grown crystal was studied by the UV–Vis spectroscopic analysis.The thermal stability of the crystal was studied by TG-DTA. The second harmonic generation (SHG) efficiency of NLT was confirmed by Kurtz Perry technique.

DMPD: Regulation of arachidonic acid release and cytosolic phospholipase A2activation. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 10080535 Regulation of arachidonic acid release and cytosolic phospholipase A2activ...on of arachidonic acid release and cytosolic phospholipase A2activation. PubmedID 10080535 Title Regulation ...of arachidonic acid release and cytosolic phospholipase A2activation. Authors Gij

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.

Effect of different polyphenol sources on the efficiency of ellagic acid release by Aspergillus niger.

Science.gov (United States)

Sepúlveda, Leonardo; de la Cruz, Reynaldo; Buenrostro, José Juan; Ascacio-Valdés, Juan Alberto; Aguilera-Carbó, Antonio Francisco; Prado, Arely; Rodríguez-Herrera, Raúl; Aguilar, Cristóbal Noé

2016-01-01

Fungal hydrolysis of ellagitannins produces hexahydroxydiphenic acid, which is considered an intermediate molecule in ellagic acid release. Ellagic acid has important and desirable beneficial health properties. The aim of this work was to identify the effect of different sources of ellagitannins on the efficiency of ellagic acid release by Aspergillus niger. Three strains of A. niger (GH1, PSH and HT4) were assessed for ellagic acid release from different polyphenol sources: cranberry, creosote bush, and pomegranate used as substrate. Polyurethane foam was used as support for solid-state culture in column reactors. Ellagitannase activity was measured for each of the treatments. Ellagic acid was quantified by high performance liquid chromatography. When pomegranate polyphenols were used, a maximum value of ellagic acid (350.21 mg/g) was reached with A. niger HT4 in solid-state culture. The highest amount of ellagitannase (5176.81 U/l) was obtained at 8h of culture when cranberry polyphenols and strain A. niger PSH were used. Results demonstrated the effect of different polyphenol sources and A. niger strains on ellagic acid release. It was observed that the best source for releasing ellagic acid was pomegranate polyphenols and A. niger HT4 strain, which has the ability to degrade these compounds for obtaining a potent bioactive molecule such as ellagic acid. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells*

Science.gov (United States)

Ali, Ramadan A.; Camick, Christina; Wiles, Katherine; Walseth, Timothy F.; Slama, James T.; Bhattacharya, Sumit; Giovannucci, David R.; Wall, Katherine A.

2016-01-01

Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca2+ mobilizing second messenger discovered to date, has been implicated in Ca2+ signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca2+ signaling or the identity of the Ca2+ stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca2+ signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca2+ signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca2+ stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca2+ signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca2+ release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. PMID:26728458

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.

Micromotors Spontaneously Neutralize Gastric Acid for pH-Responsive Payload Release.

Science.gov (United States)

Li, Jinxing; Angsantikul, Pavimol; Liu, Wenjuan; Esteban-Fernández de Ávila, Berta; Thamphiwatana, Soracha; Xu, Mingli; Sandraz, Elodie; Wang, Xiaolei; Delezuk, Jorge; Gao, Weiwei; Zhang, Liangfang; Wang, Joseph

2017-02-13

The highly acidic gastric environment creates a physiological barrier for using therapeutic drugs in the stomach. While proton pump inhibitors have been widely used for blocking acid-producing enzymes, this approach can cause various adverse effects. Reported herein is a new microdevice, consisting of magnesium-based micromotors which can autonomously and temporally neutralize gastric acid through efficient chemical propulsion in the gastric fluid by rapidly depleting the localized protons. Coating these micromotors with a cargo-containing pH-responsive polymer layer leads to autonomous release of the encapsulated payload upon gastric-acid neutralization by the motors. Testing in a mouse model demonstrate that these motors can safely and rapidly neutralize gastric acid and simultaneously release payload without causing noticeable acute toxicity or affecting the stomach function, and the normal stomach pH is restored within 24 h post motor administration. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Radiation-induced increase in the release of amino acids by isolated, perfused skeletal muscle

International Nuclear Information System (INIS)

Schwenen, M.

1989-01-01

Local exposure of the hindquarter of the rat to 15Gy of gamma-radiation resulted, 4-6h after irradiation, in increased release of amino acids by the isolated, perfused hindquarter preparation, 70% of which is skeletal muscle. This increase in release involves not only alanine and glutamine, but also those amino acids not metabolized by muscle and, therefore, released in proportion to their occurrence in muscle proteins. Because metabolic parameters and content of energy-rich phosphate compounds in muscle remain unchanged, it is unlikely that general cellular damage is the underlying cause of the radiation-induced increase in amino acid release. The findings strongly favour the hypothesis that increased availability of amino acids results from enhanced protein break-down in skeletal muscle which has its onset shortly after irradiation. This radiation-induced disturbance in protein metabolism might be one of the pathogenetic factors in the aetiology of radiation myopathy. (author)

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.

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

Evidence for the involvement of tetrahydrofolate in the demethylation of nicotine by Nicotiana plumbaginifolia cell-suspension cultures.

Science.gov (United States)

Mesnard, François; Roscher, Albrecht; Garlick, Andrew P; Girard, Sandrine; Baguet, Evelyne; Arroo, Randolf R J; Lebreton, Jacques; Robins, Richard J; Ratcliffe, GeorgeR

2002-04-01

The conversion of nicotine to nornicotine by Nicotiana plumbaginifolia Viv. cells was investigated by analysing the redistribution of label during feeding experiments with (R,S)-[2H- methyl]nicotine, (R,S)-[13C- methyl]nicotine and (R,S)-[14C- methyl]nicotine, and the results show that the N-methyl group of nicotine can be recycled into primary metabolism. Nuclear magnetic resonance (NMR) analysis of ethanolic extracts of cells grown in the presence of (R,S)-[13C- methyl]nicotine, using 1H-13C correlation spectroscopy (HMQC, HMBC), revealed the presence of [3-13C]serine and [13C- methyl]methionine. Label was also identified in a cysteinyl derivative and in several methoxylated compounds, but no evidence was obtained with either NMR or ion-trap mass spectrometry for the presence of any intermediate between nicotine and nornicotine. However, experiments with (R,S)-[14C- methyl]nicotine indicated that 70-75% of the metabolised label was released as carbon dioxide. These results are consistent with a pathway in which the oxidative hydrolysis of the nicotine methyl produces an unstable intermediate, N'-hydroxymethylnornicotine, that breaks down spontaneously to nornicotine and formaldehyde, with the formaldehyde being metabolised either directly to formate and carbon dioxide, or through the tetrahydrofolate-mediated pathways of one-carbon metabolism. However since the key intermediate, N-hydroxymethylnornicotine, could not be detected, the possibility of a direct methyl group transfer to tetrahydrofolate cannot be excluded.

Inhibition of basophil histamine release by gangliosides. Further studies on the significance of cell membrane sialic acid in the histamine release process

DEFF Research Database (Denmark)

Jensen, C; Norn, S; Thastrup, Ole

1987-01-01

with the glucolipid mixture increased the sialic acid content of the cells, and this increase was attributed to an insertion of gangliosides into the cell membrane. The inhibition of histamine release was abolished by increasing the calcium concentration, which substantiates our previous findings that cell membrane......Histamine release from human basophils was inhibited by preincubation of the cells with a glucolipid mixture containing sialic acid-containing gangliosides. This was true for histamine release induced by anti-IgE, Concanavalin A and the calcium ionophore A23187, whereas the release induced by S....... aureus Wood 46 was not affected. It was demonstrated that the inhibitory capacity of the glucolipid mixture could be attributed to the content of gangliosides, since no inhibition was obtained with cerebrosides or with gangliosides from which sialic acid was removed. Preincubation of the cells...

Impulsive behavior and nicotinic acetylcholine receptors.

Science.gov (United States)

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

2012-01-01

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

Simultaneous Intercalation of 1-Naphthylacetic Acid and Indole-3-butyric Acid into Layered Double Hydroxides and Controlled Release Properties

Directory of Open Access Journals (Sweden)

Shifeng Li

2014-01-01

Full Text Available Controlled release formulations have been shown to have potential in overcoming the drawbacks of conventional plant growth regulators formulations. A controlled-release formulation of 1-naphthylacetic acid (NAA and indole-3-butyric acid (IBA simultaneous intercalated MgAl-layered double hydroxides (LDHs was prepared. The synthetic nanohybrid material was characterized by various techniques, and release kinetics was studied. NAA and IBA anions located in the gallery of MgAl-LDHs with bilayer arrangement, and the nanohybrids particles were of typical plate-like shape with the lateral size of 50–100 nm. The results revealed that NAA and IBA have been intercalated into the interlayer spaces of MgAl-LDHs. The release of NAA and IBA fits pseudo-second-order model and is dependent on temperature, pH value, and release medium. The nanohybrids of NAA and IBA simultaneously intercalated in LDHs possessed good controlled release properties.

Ultrasound stimulated release of gallic acid from chitin hydrogel matrix

Energy Technology Data Exchange (ETDEWEB)

Jiang, Huixin; Kobayashi, Takaomi, E-mail: takaomi@nagaokaut.ac.jp

2017-06-01

Ultrasound (US) stimulated drug release was examined in this study using a chitin hydrogel matrix loaded with gallic acid (GA), a drug used for wound healing and anticancer. Using phase inversion, GA-chitin hydrogels were prepared from chitin-dimethylacetamide (DMAc)/lithium chloride (LiCl) solution in the presence of GA, with 24 h exposure of the solution to water vapor. The GA release from the GA-chitin hydrogel was examined under different US powers of 0–30 W at 43 kHz. The effects of GA loading amounts in the hydrogels (0.54, 0.43, and 0.25 mg/cm{sup 3}) and chitin concentrations (0.1, 0.5, and 1 wt%) on the release behaviors were recorded under 43 kHz US exposure at 30 W. Results show that US accelerated the release efficiencies for all samples. Furthermore, the release efficiency increased concomitantly with increasing US power, GA loading amount, and decrease of the chitin concentration. The highest release rate of 0.74 μg/mL·min was obtained from 0.54 mg/cm{sup 3} of GA-loaded hydrogel fabricated from a 0.1 wt% chitin mixture solution under 43 kHz US exposure at 30 W: nine times higher than that of the sample without US exposure. The hydrogel viscoelasticity demonstrated that the US irradiation rigidified the material. FT-IR showed that US can break the hydrogen bonds in the GA-chitin hydrogels. - Highlights: • Ultrasound (US) stimulated Gallic acid (GA) release from chitin hydrogel was studied. • The release efficiency of GA from chitin hydrogel increased nine times when irradiated by 43 kHz US compared with the sample without US. • Generalized 2D correlation and deconvolution study of FT-IR showed that US could promote the GA release by breaking hydrogen bonds.

Ultrasound stimulated release of gallic acid from chitin hydrogel matrix

International Nuclear Information System (INIS)

Jiang, Huixin; Kobayashi, Takaomi

2017-01-01

Ultrasound (US) stimulated drug release was examined in this study using a chitin hydrogel matrix loaded with gallic acid (GA), a drug used for wound healing and anticancer. Using phase inversion, GA-chitin hydrogels were prepared from chitin-dimethylacetamide (DMAc)/lithium chloride (LiCl) solution in the presence of GA, with 24 h exposure of the solution to water vapor. The GA release from the GA-chitin hydrogel was examined under different US powers of 0–30 W at 43 kHz. The effects of GA loading amounts in the hydrogels (0.54, 0.43, and 0.25 mg/cm 3 ) and chitin concentrations (0.1, 0.5, and 1 wt%) on the release behaviors were recorded under 43 kHz US exposure at 30 W. Results show that US accelerated the release efficiencies for all samples. Furthermore, the release efficiency increased concomitantly with increasing US power, GA loading amount, and decrease of the chitin concentration. The highest release rate of 0.74 μg/mL·min was obtained from 0.54 mg/cm 3 of GA-loaded hydrogel fabricated from a 0.1 wt% chitin mixture solution under 43 kHz US exposure at 30 W: nine times higher than that of the sample without US exposure. The hydrogel viscoelasticity demonstrated that the US irradiation rigidified the material. FT-IR showed that US can break the hydrogen bonds in the GA-chitin hydrogels. - Highlights: • Ultrasound (US) stimulated Gallic acid (GA) release from chitin hydrogel was studied. • The release efficiency of GA from chitin hydrogel increased nine times when irradiated by 43 kHz US compared with the sample without US. • Generalized 2D correlation and deconvolution study of FT-IR showed that US could promote the GA release by breaking hydrogen bonds.

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...

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

Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids

International Nuclear Information System (INIS)

Saxena, U.; Witte, L.D.; Goldberg, I.J.

1989-01-01

Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of 125 I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid

Characterization of chitosan-magnesium aluminum silicate nanocomposite films for buccal delivery of nicotine

DEFF Research Database (Denmark)

Pongjanyakul, Thaned; Khunawattanakul, Wanwisa; Strachan, Clare J

2013-01-01

The objective of this study was to prepare and characterize chitosan-magnesium aluminum silicate (CS-MAS) nanocomposite films as a buccal delivery system for nicotine (NCT). The effects of the CS-MAS ratio on the physicochemical properties, release and permeation, as well as on the mucoadhesive...

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.

Simulating the Fate and Transport of an Acid Mine Drainage Release

Science.gov (United States)

On August 5, 2015, approximately 3 million gallons of acid mine drainage were released from the Gold King Mine into Cement Creek in the San Juan River watershed (CO, NM, UT). The release further mobilized additional metals, which resulted in a large mass of solids and dissolved m...

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.

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

Science.gov (United States)

McClernon, Francis Joseph; Froeliger, Brett; Rose, Jed E; Kozink, Rachel V; Addicott, Merideth A; Sweitzer, Maggie M; Westman, Eric C; Van Wert, Dana M

2016-07-01

Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy. © 2015 Society for the Study of Addiction.

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.

Enhancement of nitric oxide release and hemocompatibility by surface chirality of D-tartaric acid grafting

Science.gov (United States)

Han, Honghong; Wang, Ke; Fan, Yonghong; Pan, Xiaxin; Huang, Nan; Weng, Yajun

2017-12-01

Nitric Oxide (NO) generation from endogenous NO-donors catalyzed by diselenide modified biomaterials has been reported. Here we reported surface chirality by L-tartaric acid and D-tartaric acid grafting on the outermost showed a significant impact on diselenide modified biomaterials, which modulated protein adsorption, NO release and anti-platelet adhesion properties. D-tartaric acid grafted surface showed more blood protein adsorption than that of L-surfaces by QCM analysis, however, ELISA analysis disclosed less fibrinogen denatured on the D surfaces. Due to the surface ratio of selenium decreasing, NO release catalyzed by L-tartaric acid grafting on the outermost significantly decreased in comparison to that of only selenocystamine immobilized surfaces. While NO release catalyzed by D-tartaric acid grafting on the outermost didn't decrease and was similar with that of selenocystamine immobilized surfaces. Surface chirality combined with NO release had synergetic effects on platelet adhesion, and it showed the lowest number of platelets adhered on the D-tartaric acid grafted surfaces. Thus surface chirality from D-tartaric acid grafting enhanced hemocompatibility of the surface in this study. Our work provides new insights into engineering novel blood contacting biomaterials by taking into account surface chirality.

Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells

International Nuclear Information System (INIS)

Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.; Stillwell, W.

1991-01-01

Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication

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

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

Production of ascorbic acid releasing biomaterials for pelvic floor repair.

Science.gov (United States)

Mangır, Naşide; Bullock, Anthony J; Roman, Sabiniano; Osman, Nadir; Chapple, Christopher; MacNeil, Sheila

2016-01-01

An underlying abnormality in collagen turnover is implied in the occurrence of complications and recurrences after mesh augmented pelvic floor repair surgeries. Ascorbic acid is a potent stimulant of collagen synthesis. The aim of this study is to produce ascorbic acid releasing poly-lactic acid (PLA) scaffolds and evaluate them for their effects on extracellular matrix production and the strength of the materials. Scaffolds which contained either l-ascorbic acid (AA) and Ascorbate-2-Phosphate (A2P) were produced with emulsion electrospinning. The release of both drugs was measured by UV spectrophotometry. Human dermal fibroblasts were seeded on scaffolds and cultured for 2weeks. Cell attachment, viability and total collagen production were evaluated as well as mechanical properties. No significant differences were observed between AA, A2P, Vehicle and PLA scaffolds in terms of fibre diameter and pore size. The encapsulation efficiency and successful release of both AA and A2P were demonstrated. Both AA and A2P containing scaffolds were significantly more hydrophilic and stronger in both dry and wet states compared to PLA scaffolds. Fibroblasts produced more collagen on scaffolds containing either AA or A2P compared to cells grown on control scaffolds. This study is the first to directly compare the two ascorbic acid derivatives in a tissue engineered scaffold and shows that both AA and A2P releasing electrospun PLA scaffolds increased collagen production of fibroblasts to similar extents but AA scaffolds seemed to be more hydrophilic and stronger compared to A2P scaffolds. Mesh augmented surgical repair of the pelvic floor currently relies on non-degradable materials which results in severe complications in some patients. There is an unmet and urgent need for better pelvic floor repair materials. Our current understanding suggests that the ideal material should be able to better integrate into sites of implantation both biologically and mechanically. The impact of

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.

Ultraviolet B irradiation induces changes in the distribution and release of arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture

International Nuclear Information System (INIS)

Punnonen, K.; Puustinen, T.; Jansen, C.T.

1987-01-01

There is increasing evidence that derivatives of 20-carbon polyunsaturated fatty acids, the eicosanoids, play an important role in the inflammatory responses of the human skin. To better understand the metabolic fate of fatty acids in the skin, the effect of ultraviolet B (UVB) irradiation (280-320 nm) on the distribution and release of 14 C-labeled arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture was investigated. Ultraviolet B irradiation induced the release of all three 14 C-labeled fatty acids from the phospholipids, especially from phosphatidylethanolamine, and this was accompanied by increased labeling of the nonphosphorus lipids. This finding suggests that UVB induces a significant liberation of eicosanoid precursor fatty acids from cellular phospholipids, but the liberated fatty acids are largely reincorporated into the nonphosphorus lipids. In conclusion, the present study suggests that not only arachidonic acid but also dihomo-gamma-linolenic acid, and eicosapentaenoic acid might be involved in the UVB irradiation-induced inflammatory reactions of human skin

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

The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia

DEFF Research Database (Denmark)

Thomsen, Morten Skøtt; Mikkelsen, Jens D

2012-01-01

The anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition...

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.

In vitro release of arachidonic acid and in vivo responses to respirable fractions of cotton dust

International Nuclear Information System (INIS)

Thomson, T.A.; Edwards, J.H.; Al-Zubaidy, T.S.; Brown, R.C.; Poole, A.; Nicholls, P.J.

1986-01-01

It was considered that the fall in lung function seen after exposure to cotton dust may be attributable in part to the activity of arachidonic acid metabolites, such as leucotrienes as well as to the more established release of histamine by cotton dust. However, we found that cotton and barley dusts elicited poor release of arachidonic acid from an established macrophage like cell line compared with that observed with other organic dusts. In the experimental animal, pulmonary cellular responses to both cotton and barley dust were similar to those evoked by moldy hay and pigeon dropping dusts, although after multiple doses a more severe response was seen to cotton and barley. Since both moldy hay and pigeon droppings elicit a greater arachidonic acid release than cotton or barley, a role for arachidonic acid in inducing the cellular response is less likely than other factors. There are limitations to our conclusions using this system, i.e., the arachidonic acid may be released in a nonmetabolized form, although it is noted that the two dusts with the greatest arachidonic acid release produce their clinical responses in humans largely by hypersensitivity mechanisms

Uptake in the pancreatic islets of nicotimamide, nicotinic acid and tryptophan and their ability to prevent streptozotocin diabetes in mice

Energy Technology Data Exchange (ETDEWEB)

Tjaelve, H; Wilander, E [Uppsala Univ. (Sweden)

1976-01-01

The uptake of the nicotinamide adenine dinucleotide (NAD)-precursors nicotinamide, nicotinic acid and tryptophan in the pancreatic islets of mice was studied by use of autoradio-graphical methods. The ability of these substances to prevent streptozotocin diabetes was studied in the same species. It was found that only nicotinamide was strongly accumulated in the pancreatic islets and nicotinamide was also the only NAD-precursor which protected against the streptozotocin diabetes. Apparently there is a relationship between the ability of the NAD-precursors to be taken up in the pancreatic islets and their ability to prevent streptozotocin diabetes.

Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells.

Science.gov (United States)

Ali, Ramadan A; Camick, Christina; Wiles, Katherine; Walseth, Timothy F; Slama, James T; Bhattacharya, Sumit; Giovannucci, David R; Wall, Katherine A

2016-02-26

Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca(2+) mobilizing second messenger discovered to date, has been implicated in Ca(2+) signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca(2+) signaling or the identity of the Ca(2+) stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca(2+) signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca(2+) signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca(2+) stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca(2+) signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca(2+) release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

[Shikimic acid inhibits the degranulation and histamine release in RBL-2H3 cells].

Science.gov (United States)

Chen, Xianyong; Zheng, Qianqian; Liu, Wei; Yu, Lingling; Wang, Jinling; Li, Shigang

2017-05-01

Objective To study the effects of shikimic acid on the proliferation of rat RBL-2H3 cells and the degranulation of the cells induced by C48/80 and its mechanism. Methods MTT assay was performed to measure the proliferation of RBL-2H3 cells treated with 3, 10, 30 μg/mL shikimic acid. Toluidine blue staining was used to observe the degranulation of RBL-2H3 cells. The release of β-hexosaminidase from RBL-2H3 cells treated with 0, 12.5, 25, 50, 80, 100 μg/mL C48/80 was determined by substrate assay. ELISA was used to detect the histamine content in the supernatant of each treated group. Results Shikimic acid at 3, 10, 300 μg/mL had no obvious inhibitory effect on the proliferation of RBL-2H3 cells. There was a dose-effect relationship between the degranulation of RBL-2H3 cells and C48/80 concentration. Shikimic acid inhibited the degranulation of RBL-2H3 cells compared with the positive control group, the β-hexosaminidase release rate and histamine release were significantly reduced in RBL-2H3 cells treated with shikimic acid and C48/80. Conclusion Shikimic acid can inhibit the degranulation of RBL-2H3 cells and reduce histamine release.

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

International Nuclear Information System (INIS)

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

1997-01-01

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

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

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.

The acute effects of nicotine on the subjective and behavioural responses to denicotinized tobacco in dependent smokers.

Science.gov (United States)

Barrett, Sean P; Darredeau, Christine

2012-06-01

Both nicotine and various non-nicotine smoking factors are believed to contribute to tobacco addiction but their relative roles remain incompletely understood. This study aimed to help clarify these roles by examining acute interactions between nicotine and denicotinized tobacco (DT). During two randomized blinded sessions, the effects of a quick-release 4 mg nicotine lozenge (NL) versus placebo lozenge (PL) on the subjective and behavioural responses to DT were examined in 27 (14 men) dependent, daily smokers. Participants were administered NL or PL for 30 min before receiving one initial DT cigarette. Participants could then earn additional DT cigarette puffs over the following 60 min. Subjective state was assessed using the Questionnaire of Smoking Urges-Brief and visual analogue scales at baseline, postlozenge and postinitial DT cigarette. Relative to PL, NL was associated with increased alertness as well as with reduced levels of DT self-administration (Pwomen (P<0.01). Moreover, DT administration was associated with increased ratings of 'pleasant', 'satisfied', 'stimulated' and 'relaxed', as well as with decreased ratings of 'anxious' (P's<0.01), independent of lozenge condition. The findings suggest that both nicotine and non-nicotine smoking factors may make important contributions towards the addictive properties of tobacco.

Ultraviolet radiation stimulates the release of arachidonic acid from mammalian cells in culture

International Nuclear Information System (INIS)

De Leo, V.A.; Hanson, D.; Weinstein, I.B.; Harber, L.C.

1985-01-01

C3H 10T1/2 cells in culture were prelabelled with [ 3 H]arachidonic acid and exposed to UVB radiation. Almost immediately after irradiation cells released labelled arachidonate metabolites into media in a dose dependent manner. This release was inhibited by removing calcium ions from the system and by the addition of dexamethasone and parabromophenacyl bromide to the system. This suggests that the UVB stimulated release of arachidonic acid from membrane phospholipids is, in part, mediated by a phospholipase A 2 enzyme system. Thin layer chromatographic examination of media extracts revealed a dose dependent UVB stimulation of prostaglandin production by cultured cells. (author)

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.

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.

Science.gov (United States)

Hofsäss, Martin A; Souza, Jacqueline de; Silva-Barcellos, Neila M; Bellavinha, Karime R; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Parr, Alan; Langguth, Peter; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Mehta, Mehul U; Dressman, Jennifer B

2017-12-01

This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data for higher doses of 1-5 mg are inconclusive. Following a conservative approach, folic acid is classified as a Biopharmaceutics Classification System class IV compound until more reliable data become available. Commensurate with its solubility characteristics, the results of dissolution studies indicated that none of the folic acid products evaluated showed rapid dissolution in media at pH 1.2 or 4.5. Therefore, according to the current criteria of the Biopharmaceutics Classification System, the biowaiver approval procedure cannot be recommended for immediate-release solid oral dosage forms containing folic acid. Copyright © 2017 American Pharmacists Association®. All rights reserved.

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

Synthesis, characterization and in vitro hydrolysis of a gemfibrozil-nicotinic acid codrug for improvement of lipid profile.

Science.gov (United States)

Qandil, Amjad M; Rezigue, Meriem M; Tashtoush, Bassam M

2011-06-14

Combination therapy of fibrates and nicotinic acid has been reported to be synergistic. Herein, we describe a covalent codrug of gemfibrozil (GEM) and nicotinic acid (NA) that was synthesized and characterized by (1)H NMR, (13)C NMR, FT-IR, MS analysis and elemental analysis. A validated HPLC method was developed that allows for the accurate quantitative determination of the codrug and its hydrolytic products that are formed during the in vitro chemical and enzymatic hydrolysis. The physico-chemical properties of codrug were improved compared to its parent drugs in term of water solubility and partition coefficient. The kinetics of hydrolysis of the codrug was studied using accelerated hydrolysis experiments at high temperatures in aqueous phosphate buffer solution in pH 1.2, 6.8 and 7.4. Using the Arrhenius equation, the extrapolated half-life at 37°C were 289 days at pH 1.2 for the codrug and 130 and 20,315 days at pH 6.8 for the codrug and gemfibrozil 2-hydroxyethyl ester (GHEE), respectively. The shortest half-lives were at pH 7.4; 42 days for the codrug and 5837 days for GHEE, respectively. The hydrolysis of the latter was studied, alone, at 80°C and pH 1.2 and compared to its hydrolysis when it is produced from the codrug using similar conditions. The k(obs) was found in both cases to be 1.60×10(-3)h(-1). The half-lives in plasma were 35.24 min and 26.75 h for the codrug and GHEE, respectively. With regard to liver homogenate, the hydrolysis half-lives were 1.96 min and 48.13 min for the codrug and GHEE, respectively. It can be expected that in vivo, the codrug will liberate NA immediately in plasma then GEM will be liberated from its 2-hydroxyethyl ester in the liver. Copyright © 2011 Elsevier B.V. All rights reserved.

Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes.

Science.gov (United States)

O'Dwyer, Aoife M; Lajczak, Natalia K; Keyes, Jennifer A; Ward, Joseph B; Greene, Catherine M; Keely, Stephen J

2016-08-01

Monocytes are critical to the pathogenesis of inflammatory bowel disease (IBD) as they infiltrate the mucosa and release cytokines that drive the inflammatory response. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with anti-inflammatory actions, has been proposed as a potential new therapy for IBD. However, its effects on monocyte function are not yet known. Primary monocytes from healthy volunteers or cultured U937 monocytes were treated with either the proinflammatory cytokine, TNFα (5 ng/ml) or the bacterial endotoxin, lipopolysaccharide (LPS; 1 μg/ml) for 24 h, in the absence or presence of UDCA (25-100 μM). IL-8 release into the supernatant was measured by ELISA. mRNA levels were quantified by qPCR and changes in cell signaling proteins were determined by Western blotting. Toxicity was assessed by measuring lactate dehydrogenase (LDH) release. UDCA treatment significantly attenuated TNFα-, but not LPS-driven, release of IL-8 from both primary and cultured monocytes. UDCA inhibition of TNFα-driven responses was associated with reduced IL-8 mRNA expression. Both TNFα and LPS stimulated NFκB activation in monocytes, while IL-8 release in response to both cytokines was attenuated by an NFκB inhibitor, BMS-345541. Interestingly, UDCA inhibited TNFα-, but not LPS-stimulated, NFκB activation. Finally, TNFα, but not LPS, induced phosphorylation of TNF receptor associated factor (TRAF2), while UDCA cotreatment attenuated this response. We conclude that UDCA specifically inhibits TNFα-induced IL-8 release from monocytes by inhibiting TRAF2 activation. Since such actions would serve to dampen mucosal immune responses in vivo, our data support the therapeutic potential of UDCA for IBD. Copyright © 2016 the American Physiological Society.

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...

Prolonged local anesthetic action through slow release from poly (lactic acid co castor oil).

Science.gov (United States)

Sokolsky-Papkov, Marina; Golovanevski, Ludmila; Domb, Abraham J; Weiniger, Carolyn F

2009-01-01

To evaluate a new formulation of bupivacaine loaded in an injectable fatty acid based biodegradable polymer poly(lactic acid co castor oil) in prolonging motor and sensory block when injected locally. The polyesters were synthesized from DL: -lactic acid and castor oil with feed ratio of 4:6 and 3:7 w/w. Bupivacaine was dispersed in poly(fatty ester) liquid and tested for drug release in vitro. The polymer p(DLLA:CO) 3:7 loaded with 10% bupivacaine was injected through a 22G needle close to the sciatic nerve of ICR mice and the duration of sensory and motor nerve blockade was measured. The DL: -lactic acid co castor oil p(DLLA:CO) 3:7 released 65% of the incorporated bupivacaine during 1 week in vitro. Single injection of 10% bupivacaine loaded into this polymer caused motor block that lasted 24 h and sensory block that lasted 48 h. Previously we developed a ricinoleic acid based polymer with incorporated bupivacaine which prolonged anesthesia to 30 h. The new polymer poly(lactic acid co castor oil) 3:7 provides slow release of effective doses of the incorporated local anesthetic agent and prolongs anesthesia to 48 h.

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

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

Science.gov (United States)

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

2015-01-01

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

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.

In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

Directory of Open Access Journals (Sweden)

Wen-Hao Wei

2015-03-01

Full Text Available Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD chemical conjugate with different degree of substitution (DS of deoxycholic acid (DOCA were prepared. The degree of substitution (DS was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX as the model drug. The human cervical cancer (HeLa cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE, which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.

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

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

Science.gov (United States)

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

2017-09-01

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

Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

Science.gov (United States)

Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

2017-01-01

Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

[Effect of glucocorticoides on the release of amino acids in the perfused rat hindquarter (author's transl)].

Science.gov (United States)

Thienhaus, R; Tharandt, L; Zais, U; Staib, W

1975-06-01

The release of amino acids by skeletal muscle was studied in the isolated perfused rat hindquarter. Adrenalectomy depressed the formation of glutamine and alanine as well as the efflux of all other amino acids measured. Betamethasone--a synthetic glucocorticoid--caused a significant increase in the efflux of nearly all amino acids up to the level of normal controls. The release of amino acids was also increased in perfused hindquarters of diabetic rats. On the other hand, insulin exhibited a depressing effect on the release of amino acids by hindquarters of normal rats. The metabolic integrity of the muscle tissue was proved by measuring creatine phosphate, ATP, ADP and water content as well as by the significant insulin effect on glucose uptake and on [14C]leucine incorporation into muscle proteins.

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.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Directory of Open Access Journals (Sweden)

A. Zago

2012-01-01

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

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.

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

Controlled Release of 5-Aminosalicylic Acid (5-ASA from New Biodegradable Polyurethanes

Directory of Open Access Journals (Sweden)

El-Refaie Kenawy

2010-03-01

Full Text Available Segmented polyurethanes containing azo aromatic groups in the main chain were synthesized by reaction of 3,3'-azobis(6-hydroxybenzoic acid (ABHB, 5-[4-(hydroxyphenylazo] salicylic acid (HPAS, and 5-[1-hydroxynaphthylazo] salicylic acid (HNAS with hexamethylenediisocyanate (HDI. All synthesized monomers and polymers were characterized by elemental analysis, FTIR, 1H-NMR spectra, TGA and DSC analysis. All the synthesized azo polymers showed good thermal stability and the onset decomposition temperature of all these polymers was found to be above 195 ºC under nitrogen atmosphere.The release of 5-ASA under physiological conditions (pH = 7.8 and pH = 1.5 was investigated at body temperature (37 ºC. The release rate of 5-ASA increased with increasing pH (i.e., 7.8 > 1.5.

Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain.

Science.gov (United States)

Cumming, Paul; Rosa-Neto, Pedro; Watanabe, Hideaki; Smith, Donald; Bender, Dirk; Clarke, Paul B S; Gjedde, Albert

2003-07-01

Positive reinforcing properties of nicotine and the psychostimulants have been attributed to elevated dopamine release in the basal ganglia. It is well known that the specific binding of [(11)C]raclopride to dopamine D(2,3) receptors in living striatum is reduced by cocaine and amphetamines, revealing increased competition between endogenous dopamine and [(11)C]raclopride for dopamine D(2,3) receptors. However, the sensitivity of [(11)C]raclopride binding to nicotine-induced dopamine release is less well documented. In order to provide the basis for mapping effects of nicotine, we first optimized reference tissue methods for quantifying [(11)C]raclopride binding sites in striatum of living pigs (n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using [(15)O]water. Neither a low dose of nicotine (50 mu kg(-1), iv) nor a high dose of nicotine (500 microg kg(-1), iv) altered CBF in the pig brain, an important condition for calculating the binding of radioligands when using a reference tissue to estimate the free ligand concentration. The methods of Logan and of Lammertsma were compared using the cerebellum or the occipital cortex as reference tissues for calculating the binding potential (pB) of [(11)C]raclolpride in brain. Irrespective of the method used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric, with highest binding in the left caudate and right putamen. Test-retest estimates of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine reduced the pB of [(11)C]raclopride by 10% in a cluster of voxels in the left anteroventral striatum, but this effect did not persist after correction for multiple comparisons. The high dose of nicotine (n = 9) acutely reduced pB by 10% bilaterally in the ventral striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and caudally into the caudate and putamen. Evidently, nicotine challenge enhances the competition

Modulation of release of [3H]acetylcholine in the major pelvic ganglion of the rat.

Science.gov (United States)

Somogyi, G T; de Groat, W C

1993-06-01

Cholinergic modulation of [3H]acetylcholine release evoked by electrical stimulation was studied in the rat major pelvic ganglion, which was prelabeled with [3H]choline. Acetylcholine (ACh) release was independent of the frequency of stimulation; 0.3 Hz produced the same volley output as 10 Hz. Tetrodotoxin (1 microM) or omission of Ca2+ from the medium abolished ACh release. The M1 receptor agonist (4-hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride (McN-A 343, 50 microM) increased release (by 136%), whereas the M2 muscarinic agonist oxotremorine (1 microM) decreased ACh release (by 22%). The muscarinic antagonists, atropine (1 microM) or pirenzepine (M1 selective, 1 microM), did not change ACh release. However, pirenzepine (1 microM) blocked the facilitatory effect of McN-A 343, and atropine (1 microM) blocked the inhibitory effect of oxotremorine. The cholinesterase inhibitor physostigmine (1-5 microM), the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10 microM), and the nicotinic antagonist D-tubocurarine (50 microM) did not change ACh release. 4-Aminopyridine, a K+ channel blocker, significantly increased the release (by 146%). Seven days after decentralization of the major pelvic ganglion, the evoked release of ACh was abolished. It is concluded that release of ACh occurs from the preganglionic nerve terminals rather than from the cholinergic cell bodies and is not modulated by actions of endogenous ACh on either muscarinic or nicotinic autoreceptors. These data confirm and extend previous electrophysiological findings indicating that synapses in the major pelvic ganglion have primarily a relay function.

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

Science.gov (United States)

Bush, Derek; Goniewicz, Maciej L

2015-06-01

Nicotine deposited on the surfaces has been shown to react with airborne chemicals leading to formation of carcinogens and contributing to thirdhand exposure. While prior studies revealed nicotine residues in tobacco smokers' homes, none have examined the nicotine residue in electronic cigarette (e-cigarette) users' homes. We measured nicotine on the surfaces in households of 8 e-cigarette users, 6 cigarette smokers, and 8 non-users of nicotine-containing products in Western New York, USA. Three surface wipe samples were taken from the floor, wall and window. Nicotine was extracted from the wipes and analyzed using gas chromatography. Half of the e-cigarette users' homes had detectable levels of nicotine on surfaces whereas nicotine was found in all of the tobacco cigarette smokers' homes. Trace amounts of nicotine were also detected in half of the homes of non-users of nicotine-containing products. Nicotine levels in e-cigarette users homes was significantly lower than that found in cigarette smokers homes (average concentration 7.7±17.2 vs. 1303±2676 μg/m2; pe-cigarette users and non-users (p>0.05). Nicotine is a common contaminant found on indoor surfaces. Using e-cigarettes indoors leads to significantly less thirdhand exposure to nicotine compared to smoking tobacco cigarettes. Copyright © 2015 Elsevier B.V. All rights reserved.

Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS).

Science.gov (United States)

Leigh, Noel J; Lawton, Ralph I; Hershberger, Pamela A; Goniewicz, Maciej L

2016-11-01

E-cigarettes or electronic nicotine delivery systems (ENDS) are designed to deliver nicotine-containing aerosol via inhalation. Little is known about the health effects of flavoured ENDS aerosol when inhaled. Aerosol from ENDS was generated using a smoking machine. Various types of ENDS devices or a tank system prefilled with liquids of different flavours, nicotine carrier, variable nicotine concentrations and with modified battery output voltage were tested. A convenience sample of commercial fluids with flavour names of tobacco, piña colada, menthol, coffee and strawberry were used. Flavouring chemicals were identified using gas chromatography/mass spectrometry. H292 human bronchial epithelial cells were directly exposed to 55 puffs of freshly generated ENDS aerosol, tobacco smoke or air (controls) using an air-liquid interface system and the Health Canada intense smoking protocol. The following in vitro toxicological effects were assessed: (1) cell viability, (2) metabolic activity and (3) release of inflammatory mediators (cytokines). Exposure to ENDS aerosol resulted in decreased metabolic activity and cell viability and increased release of interleukin (IL)-1β, IL-6, IL-10, CXCL1, CXCL2 and CXCL10 compared to air controls. Cell viability and metabolic activity were more adversely affected by conventional cigarettes than most tested ENDS products. Product type, battery output voltage and flavours significantly affected toxicity of ENDS aerosol, with a strawberry-flavoured product being the most cytotoxic. Our data suggest that characteristics of ENDS products, including flavours, may induce inhalation toxicity. Therefore, ENDS users should use the products with caution until more comprehensive studies are performed. 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/.

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.

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

Science.gov (United States)

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

2018-07-01

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

Vitamin E Nicotinate

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.

Uranium Release from Acidic Weathered Hanford Sediments: Single-Pass Flow-Through and Column Experiments.

Science.gov (United States)

Wang, Guohui; Um, Wooyong; Wang, Zheming; Reinoso-Maset, Estela; Washton, Nancy M; Mueller, Karl T; Perdrial, Nicolas; O'Day, Peggy A; Chorover, Jon

2017-10-03

The reaction of acidic radioactive waste with sediments can induce mineral transformation reactions that, in turn, control contaminant fate. Here, sediment weathering by synthetic uranium-containing acid solutions was investigated using bench-scale experiments to simulate waste disposal conditions at Hanford's cribs (Hanford, WA). During acid weathering, the presence of phosphate exerted a strong influence over uranium mineralogy and a rapidly precipitated, crystalline uranium phosphate phase (meta-ankoleite [K(UO 2 )(PO 4 )·3H 2 O]) was identified using spectroscopic and diffraction-based techniques. In phosphate-free system, uranium oxyhydroxide minerals such as K-compreignacite [K 2 (UO 2 ) 6 O 4 (OH) 6 ·7H 2 O] were formed. Single-pass flow-through (SPFT) and column leaching experiments using synthetic Hanford pore water showed that uranium precipitated as meta-ankoleite during acid weathering was strongly retained in the sediments, with an average release rate of 2.67 × 10 -12 mol g -1 s -1 . In the absence of phosphate, uranium release was controlled by dissolution of uranium oxyhydroxide (compreignacite-type) mineral with a release rate of 1.05-2.42 × 10 -10 mol g -1 s -1 . The uranium mineralogy and release rates determined for both systems in this study support the development of accurate U-release models for the prediction of contaminant transport. These results suggest that phosphate minerals may be a good candidate for uranium remediation approaches at contaminated sites.

Uranium Release from Acidic Weathered Hanford Sediments: Single-Pass Flow-Through and Column Experiments

Energy Technology Data Exchange (ETDEWEB)

Wang, Guohui [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Um, Wooyong [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Pohang University of Science and Technology (POSTECH), Pohang, South Korea; Wang, Zheming [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Reinoso-Maset, Estela [Sierra; Washton, Nancy M. [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Mueller, Karl T. [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Perdrial, Nicolas [Department; Department; O’Day, Peggy A. [Sierra; Chorover, Jon [Department

2017-09-21

The reaction of acidic radioactive waste with sediments can induce mineral transformation reactions that, in turn, control contaminant fate. Here, sediment weathering by synthetic uranium-containing acid solutions was investigated using bench-scale experiments to simulate waste disposal conditions at Hanford’s cribs, USA. During acid weathering, the presence of phosphate exerted a strong influence over uranium mineralogy and a rapidly precipitated, crystalline uranium phosphate phase (meta-ankoleite [K(UO2)(PO4)·3H2O]) was identified using spectroscopic and diffraction-based techniques. In phosphate-free system, uranium oxyhydroxide minerals such as K-compreignacite [K2(UO2)6O4(OH)6·7H2O] were formed. Single-pass flow-through (SPFT) and column leaching experiments using synthetic Hanford pore water showed that uranium precipitated as meta-ankoleite during acid weathering was strongly retained in the sediments, with an average release rate of 2.67E-12 mol g-1 s-1. In the absence of phosphate, uranium release was controlled by dissolution of uranium oxyhydroxide (compreignacite-type) mineral with a release rate of 1.05-2.42E-10 mol g-1 s-1. The uranium mineralogy and release rates determined for both systems in this study support the development of accurate U-release models for prediction of contaminant transport. These results suggest that phosphate minerals may be a good candidate for uranium remediation approaches at contaminated sites.

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.

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...

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).

Liquid-Phase Heat-Release Rates of the Systems Hydrazine-Nitric Acid and Unsymmetrical Dimethylhydrazine-Nitric Acid

Science.gov (United States)

Somogyi, Dezso; Feiler, Charles E.

1960-01-01

The initial rates of heat release produced by the reactions of hydrazine and unsymmetrical dimethylhydrazine with nitric acid were determined in a bomb calorimeter under conditions of forced mixing. Fuel-oxidant weight ratio and injection velocity were varied. The rate of heat release apparently depended on the interfacial area between the propellants. Above a narrow range of injection velocities representing a critical amount of interfacial area, the rates reached a maximum and were almost constant with injection velocity. The maximum rate for hydrazine was about 70 percent greater than that for unsymmetrical dimethylhydrazine. The total heat released did not vary with mixture ratio over the range studied.

A sol-gel based molecular imprint incorporating carbon dots for fluorometric determination of nicotinic acid

International Nuclear Information System (INIS)

Zuo, Pengli; Gao, Junfa; Liu, Jianha; Zhao, Mingming; Zhao, Jiahong; Peng, Jun; Zuo, Pengjian; He, Hua

2016-01-01

We are introducing functionalized carbon dots (C-dots) coated with a shell of molecularly imprinted sol-gel as a new tool in molecular imprint-based detection. Specifically, an imprint recognizing nicotinic acid (NA) was prepared in two steps. The first involves pyrolytic decomposition of citric acid in the presence of aminopropyltriethoxysilane to yield triethoxysilyl-modified C-dots with a typical size of 2.8 ± 1.1 nm. These are then polycondensed in the presence of tetraethoxysilane and NA at room temperature to give spherical silica nanoparticles (SiNPs) with a typical size of ∼300 nm and containing C-dots and NA in the silica matrix. NA was then removed by extraction. The resulting SiNPs are well permeable to NA, photostable, display strong blue luminescence and can bind NA fairly selectively. The fluorometric detection scheme is based on the finding that increasing concentrations of NA quench the fluorescence of the C-dots in the SiNPs. NA can be determined by this method in the 0.5 to 10.5 μM concentration range, with a 12.6 nM detection limit. The composite was successfully utilized as a fluorescent probe for the determination of NA in spiked human urine samples. The method is believed to have a wider scope in being applicable to other analytes that are capable of quenching the fluorescence of C-dots. (author)

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.

Ibuprofen-loaded poly(lactic-co-glycolic acid films for controlled drug release

Directory of Open Access Journals (Sweden)

Pang JM

2011-04-01

Full Text Available Jianmei Pang1, Yuxia Luan1, Feifei Li1, Xiaoqing Cai1, Jimin Du2, Zhonghao Li31School of Pharmaceutical Science, Shandong University, Jinan, Shandong Province, PR China; 2School of Chemistry and Chemical Engineering, Anyang Normal University, Henan Province, PR China; 3School of Materials Science and Engineering, Shandong University, Jinan, Shandong Province, PR ChinaAbstract: Ibuprofen- (IBU loaded biocompatible poly(lactic-co-glycolic acid (PLGA films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.Keywords: ibuprofen, controlled release, poly(lactic-co-glycolic acid, films

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

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

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

Directory of Open Access Journals (Sweden)

Islam Gamaleddin

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

Hydrocortisone selectively inhibits IgE-dependent arachidonic acid release from rat peritoneal mast cells

International Nuclear Information System (INIS)

Heiman, A.S.; Crews, F.T.

1984-01-01

Purified rat mst cells were used to study the effects of antiinflammatory steroids on the release of [1-14C]-arachidonic acid ([1-14C]AA) and metabolites. Mast cell were incubated overnight with glucocorticoids, [1-14C]AA incorporated into cellular phospholipids and the release of [1-14C]AA, and metabolites determined using a variety of secretagogues. Release of [1-14C]AA and metabolites by concanavalin A, the antigen ovalbumin and anti-immunoglobulin E antibody was markedly reduced by glucocorticoid treatment. Neither the total incorporation of [1-14C]AA nor the distribution into phospholipids was altered by hydrocortisone pretreatment. Glucocorticoid pretreatment did not alter [1-14C]AA release stimulated by somatostatin, compound 48/80, or the calcium ionophore, A23187. These data indicate that antiinflammatory steroids selectively inhibit immunoglobulin dependent release of arachidonic acid from rat mast cells. These findings question the role of lipomodulin and macrocortin as general phospholipase inhibitors and suggest that they may be restricted to immunoglobulin stimuli

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.

Profiling of the Contents of Amino Acids, Water-Soluble Vitamins, Minerals, Sugars and Organic Acids in Turkish Hazelnut Varieties

Directory of Open Access Journals (Sweden)

Taş Neslihan Göncüoğlu

2018-09-01

Full Text Available Proximate composition, profiles of amino acids, sugars, organic acids, vitamins and minerals of fourteen Turkish hazelnut varieties harvested in 2013 and 2014 were investigated. Glutamic acid, arginine and aspartic acid were the most predominant amino acids, representing of about 50% of hazelnut protein. Individual amino acid profiles showed significant differences depending upon the harvest year (p<0.05. Concentration of sucrose was the highest followed by fructose, glucose, stachyose, raffinose and myo-inositol, respectively. Phytic acid was predominant organic acid in all varieties, followed by malic acid. Independent of the variety, hazelnuts were rich in pantothenic acid, nicotinic acid, pyridoxal, biotin, thiamine, nicotinamide. Pantothenic and nicotinic acid were significantly higher in most of the varieties in harvest year 2014. Potassium was the most predominant mineral, followed by magnesium, calcium, sodium, manganese, zinc, iron and copper, respectively.

Neutralization method for a hydrofluoric acid release

International Nuclear Information System (INIS)

Williams, D.L.; Deacon, L.E.

1976-01-01

A laboratory investigation of methods for neutralizing a release at the hydrofluoric acid tank farm at the Portsmouth Gaseous Diffusion Plant has revealed that the best neutralization method incorporates the use of a lime/water slurry. In this method, settling of suspended solids in the liquid is enhanced by the application of sodium dodecyl sulfate, which causes immediate flocculation and settling. Dilution and expulsion of the supernatant liquid above the flocculated solids result in an effluent which meets the one part per million fluoride limit established by the U.S. Environmental Protection Agency. A fluoride specific ion electrode is used to determine fluoride concentration. This method presently is being adapted for use in the hydrofluoric acid tank farm and is being considered for use at the plant's fluorine generation facility. It could be adapted for use in any facility that contains fluoride in aqueous solution

Nicotine transport in lung and non-lung epithelial cells.

Science.gov (United States)

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

2017-11-01

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

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

Science.gov (United States)

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

2017-05-15

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

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

Science.gov (United States)

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

2014-09-25

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

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

Science.gov (United States)

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

2016-02-20

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

A convenient synthesis of sup 14 C-cotinine from sup 14 C-nicotine

Energy Technology Data Exchange (ETDEWEB)

Desai, D.H.; Djordjevic, M.V.; Amin, S. (American Health Foundation, Valhalla, NY (USA). Naylor Dana Inst. for Disease Prevention)

1991-03-01

A convenient synthesis with analytical monitoring of {sup 14}C-cotinine is reported. {sup 14}C-Nicotine was converted into {sup 14}C-dibromocotinine hydrobromide perbromide. Debromination, achieved by using Zn dust/acetic acid, resulted in high yields (71%) of {sup 14}C-cotinine. (author).

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

Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

Energy Technology Data Exchange (ETDEWEB)

Zargarian, S. Sh.; Haddadi-Asl, V., E-mail: haddadi@aut.ac.ir; Hematpour, H. [Amirkabir University of Technology, Department of Polymer Engineering and Color Technology (Iran, Islamic Republic of)

2015-05-15

Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite.

Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

International Nuclear Information System (INIS)

Zargarian, S. Sh.; Haddadi-Asl, V.; Hematpour, H.

2015-01-01

Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite

Maternal exposure of rats to nicotine via infusion during gestation produces neurobehavioral deficits and elevated expression of glial fibrillary acidic protein in the cerebellum and CA1 subfield in the offspring at puberty

International Nuclear Information System (INIS)

Abdel-Rahman, Ali; Dechkovskaia, Anjelika M.; Sutton, Jazmine M.; Chen, Wei-Chung; Guan, Xiangrong; Khan, Wasiuddin A.; Abou-Donia, Mohamed B.

2005-01-01

Maternal smoking during pregnancy is known to be a significant contributor to developmental neurological health problems in the offspring. In animal studies, nicotine treatment via injection during gestation has been shown to produce episodic hypoxia in the developing fetus. Nicotine delivery via mini osmotic pump, while avoiding effects due to hypoxia-ischemia, it also provides a steady level of nicotine in the plasma. In the present study timed-pregnant Sprague-Dawley rats (300-350 g) were treated with nicotine (3.3 mg/kg, in bacteriostatic water via s.c. implantation of mini osmotic pump) from gestational days (GD) 4-20. Control animals were treated with bacteriostatic water via s.c. implantation of mini osmotic pump. Offspring on postnatal day (PND) 30 and 60, were evaluated for changes in the ligand binding for various types of nicotinic acetylcholine receptors and neuropathological alterations. Neurobehavioral evaluations for sensorimotor functions, beam-walk score, beam-walk time, incline plane and grip time response were carried out on PND 60 offspring. Beam-walk time and forepaw grip time showed significant impairments in both male and female offspring. Ligand binding densities for [ 3 H]epibatidine, [ 3 H]cytisine and [ 3 H]α-bungarotoxin did not show any significant changes in nicotinic acetylcholine receptors subtypes in the cortex at PND 30 and 60. Histopathological evaluation using cresyl violet staining showed significant decrease in surviving Purkinje neurons in the cerebellum and a decrease in surviving neurons in the CA1 subfield of hippocampus on PND 30 and 60. An increase in glial fibrillary acidic protein (GFAP) immuno-staining was observed in cerebellum white matter as well as granular cell layer of cerebellum and the CA1 subfield of hippocampus on PND 30 and 60 of both male and female offspring. These results indicate that maternal exposure to nicotine produces significant neurobehavioral deficits, a decrease in the surviving neurons and an

Effects of nicotine on cellular proliferation, cell cycle phase distribution, and macromolecular synthesis in human promyelocytic HL-60 leukaemia cells

International Nuclear Information System (INIS)

Konno, S.; Wu, J.M.; Chiao, J.W.

1986-01-01

Addition of nicotine causes a dose- and time-dependent inhibition of cell growth in the human promyelocytic HL-60 leukemia cells, with 4 mM nicotine resulting in a 50% inhibition of cellular proliferation after 48-50h. Accompanying the anticellular effect of nicotine is a significant change in the cell cycle distribution of HL-60 cells. For example, treatment with 4 mM nicotine for 20h causes an increase in the proportion of G1-phase cells (from 49% to 57%) and a significant decrease in the proportion of S-phase cells (from 41% to 32%). These results suggest that nicotine causes partial cell arrest in the G-1 phase which may in part account for its effects on cell growth. To determine whether nicotine changes the cellular uptake/transport to macromolecular precursors, HL-60 cells were treated with 216 mM nicotine for 30h, at the end of which time cells were labelled with ( 3 H)thymidine, ( 3 H)uridine, ( 14 C)lysine and( 35 S)methionine, the trichloroacetic acid soluble and insoluble radioactivities from each of the labelling conditions were determined. These studies show that nicotine mainly affects the ''de novo synthesis'' of proteins. (author)

In vivo human buccal permeability of nicotine

DEFF Research Database (Denmark)

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

2006-01-01

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

Bioelectronic sniffer for nicotine using enzyme inhibition.

Science.gov (United States)

Mitsubayashi, Kohji; Nakayama, Kazumi; Taniguchi, Midori; Saito, Hirokazu; Otsuka, Kimio; Kudo, Hiroyuki

2006-07-28

A novel bioelectronic sniffer for nicotine in the gas phase was developed with enzyme inhibition principle to butyrylcholinesterase activity. The bioelectronic devices for nicotine in the gas and liquid phases were constructed using a Clark-type dissolved oxygen electrode and a membrane immobilized butyrylcholinesterase and choline oxidase. After the assessment of the sensor performances to choline and butyrylcholine as pre-examinations, the characteristics of the biosensor and bio-sniffer for nicotine were evaluated in the liquid and gas phases, respectively. The sensor signal of the bio-devices with 300 micromol l(-1) of butyrylcholine decreased quickly following application of nicotine and reached to the steady-state current, thus relating the concentration of nicotine in the liquid and gas phases. The biosensor was used to measure nicotine solution from 10 to 300 micromol l(-1). In the gas-phase experiment, the current signal of the bio-sniffer was also found to be linearly to the nicotine concentration over the range of 10.0-1000 ppb including 75.0 ppb as threshold limit value (TLV) by American Conference of Governmental Industrial Hygienists (ACGIH).

Nicotine adsorption on single wall carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

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

2010-12-15

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

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.

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

Science.gov (United States)

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

2016-05-01

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

Stable isotope studies of nicotine kinetics and bioavailability

International Nuclear Information System (INIS)

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

1991-01-01

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

A study of marine pollution caused by the release of metals into seawater following acid spills.

Science.gov (United States)

Cabon, Jean-Yves; Giamarchi, Philippe; Le Floch, Stephane

2010-07-01

This study examined the potential metal pollution induced by the accidental spill of different acids into seawater. The acids sink to the bottom according to their densities and subsequently react with marine sediments. The acids selected for this study were acetic, hydrochloric, nitric, sulfuric, and phosphoric acids; the metallic elements selected were Cr, Cu, Fe, Mn, Pb and Zn. The sediment was collected in Brest Harbour. The percentages of metals released from this sediment in the presence of various concentrations of acids in seawater were important; concentrations of approximately 7 mg L(-1) for Mn and 60 mg L(-1) for Zn were observed under our experimental conditions. We also examined the rate of release of these metals from the sediment into the seawater in the presence of the different acids and under different experimental conditions. We found that most of the metallic elements were released from the sediments into the seawater during the first fifteen minutes of exposure. After this time, a high degree of pollution was induced if acids leached into seawater were not rapidly diluted. Copyright 2010 Elsevier Ltd. All rights reserved.

Evidence for inhibitory nicotinic and facilitatory muscarinic receptors in cholinergic nerve terminals of the rat urinary bladder.

Science.gov (United States)

Somogyi, G T; de Groat, W C

1992-02-01

Cholinergic prejunctional modulatory receptors on parasympathetic nerves in the rat urinary bladder were studied by measuring 3H-acetylcholine (ACh) release in muscle strips from the bladder body. Electrical field stimulation markedly increased 3H-ACh overflow in strips preloaded with 3H-choline. Oxotremorine (1 microM), an M2 receptor agonist and DMPP (10 microM) a nicotinic (N) receptor agonist decreased the release of ACh (50% and 55% respectively); whereas McN-A 343 (50 microM) an M1 receptor agonist increased the release (33%), indicating the presence of three types of modulatory receptors. The anticholinesterase agent, physostigmine in concentrations of 1, 5 and 25 microM and neostigmine (5 microM) increased ACh release (44-710%). However a low concentration of physostigmine (0.05 microM) decreased release. Pirenzepine, an M1 muscarinic antagonist or atropine blocked the increased ACh release in physostigmine-treated strips, but in normal strips pirenzepine did not change release and atropine increased release. McN-A 343 or prolonged application (15 min) of DMPP increased ACh release (376% and 391% respectively) in physostigmine-treated strips. The response to McN-A 343 was blocked by pirenzepine. d-Tubocurarine (DTC), a nicotinic receptor blocker, enhanced ACh release in the presence of physostigmine but proved to be ineffective in normal preparations. These findings suggest that all three cholinergic receptors (M1 facilitatory, N inhibitory and M2 inhibitory) are activated by endogenous ACh in physostigmine treated preparations whereas only M2-inhibitory receptors are activated in normal preparations. It will be important in future studies to determine whether M1 and M2 mechanisms can also be activated under more physiological conditions in the bladder and whether they are present at other cholinergic synapses.

Inside-out neuropharmacology of nicotinic drugs.

Science.gov (United States)

Henderson, Brandon J; Lester, Henry A

2015-09-01

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

Tolerance to and cross tolerance between ethanol and nicotine.

Science.gov (United States)

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

1988-02-01

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

Transdermal nicotine absorption handling e-cigarette refill liquids.

Science.gov (United States)

Maina, Giovanni; Castagnoli, Carlotta; Passini, Valter; Crosera, Matteo; Adami, Gianpiero; Mauro, Marcella; Filon, Francesca Larese

2016-02-01

The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids. Copyright © 2015 Elsevier Inc. All rights reserved.

Overexpression of CRF in the BNST diminishes dysphoria but not anxiety-like behavior in nicotine withdrawing rats.

Science.gov (United States)

Qi, Xiaoli; Guzhva, Lidia; Yang, Zhihui; Febo, Marcelo; Shan, Zhiying; Wang, Kevin K W; Bruijnzeel, Adriaan W

2016-09-01

Smoking cessation leads to dysphoria and anxiety, which both increase the risk for relapse. This negative affective state is partly mediated by an increase in activity in brain stress systems. Recent studies indicate that prolonged viral vector-mediated overexpression of stress peptides diminishes stress sensitivity. Here we investigated whether the overexpression of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST) diminishes nicotine withdrawal symptoms in rats. The effect of nicotine withdrawal on brain reward function was investigated with an intracranial self-stimulation (ICSS) procedure. Anxiety-like behavior was investigated in the elevated plus maze test and a large open field. An adeno-associated virus (AAV) pseudotype 2/5 vector was used to overexpress CRF in the lateral BNST and nicotine dependence was induced using minipumps. Administration of the nicotinic receptor antagonist mecamylamine and cessation of nicotine administration led to a dysphoria-like state, which was prevented by the overexpression of CRF in the BNST. Nicotine withdrawal also increased anxiety-like behavior in the elevated plus maze test and large open field test and slightly decreased locomotor activity in the open field. The overexpression of CRF in the BNST did not prevent the increase in anxiety-like behavior or decrease in locomotor activity. The overexpression of CRF increased CRF1 and CRF2 receptor gene expression and increased the CRF2/CRF1 receptor ratio. In conclusion, the overexpression of CRF in the BNST prevents the dysphoria-like state associated with nicotine withdrawal and increases the CRF2/CRF1 receptor ratio, which may diminish the negative effects of CRF on mood. Published by Elsevier B.V.

Release of Polyphenols Is the Major Factor Influencing the Bioconversion of Rice Straw to Lactic Acid.

Science.gov (United States)

Chen, Xingxuan; Xue, Yiyun; Hu, Jiajun; Tsang, Yiu Fai; Gao, Min-Tian

2017-11-01

In this study, we found that p-coumaric acid (p-CA), ferulic acid (FA), and condensed tannins were released from rice straw during saccharification. The presence of polyphenols prolonged the lag phase and lowered the productivity of lactic acid. p-CA was identified as a key inhibitor. Tannins had a lower inhibitory effect than p-CA; FA had little inhibitory effect. Acid, alkaline, and ball milling pretreatments elicited different levels of polyphenol release from rice straw. Due to the different levels of polyphenol release in the pretreatment step, the enzymatic hydrolysates contained different concentrations of polyphenols. Compared with fermentation with a synthetic medium, fermentation with the hydrolysates of ball-milled rice straw provided much lower productivity and yield of lactic acid due to the presence of polyphenols. Removal of these compounds played an important role in lactic acid fermentation. When rice straw was alkaline pretreated, the hydrolysates contained few phenolic compounds, resulting in high productivity and yield of lactic acid (1.8 g/L/h and 26.7 g/100 g straw), which were comparable to those in a synthetic medium. This indicates that there is a correlation between removal of phenolic compounds and efficiency in lactic acid fermentation.

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-09-15

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. - Highlights: • Modelling of nicotine disposition in the presence of anti-nicotine antibodies • Key vaccine efficacy factors are evaluated in silico in rats and in humans. • Model predicts insufficient antibody binding in past human nicotine vaccines. • Improving immunogenicity and antibody specificity may lead to vaccine success.

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

International Nuclear Information System (INIS)

Saylor, Kyle; Zhang, Chenming

2016-01-01

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. - Highlights: • Modelling of nicotine disposition in the presence of anti-nicotine antibodies • Key vaccine efficacy factors are evaluated in silico in rats and in humans. • Model predicts insufficient antibody binding in past human nicotine vaccines. • Improving immunogenicity and antibody specificity may lead to vaccine success.

Improvement of Nicotinic Acid and Nicotinamide Analysis in Meats and Meat Products by HPLC and LC-MS/MS with Solid-Phase Extraction.

Science.gov (United States)

Hiki, Asako; Yamajima, Yukiko; Uematsu, Yoko

2016-01-01

A method for nicotinic acid (NA) and nicotinamide (NAA) analysis in meats was developed. NA and NAA were extracted from meats or meat products with metaphosphate aqueous solution. The extract was cleaned up with an Oasis MCX cartridge. The cartridge was washed with 2% acetic acid (v/v) and acetic acid-methanol solution. NA and NAA were eluted with ammonia-methanol solution. NA and NAA in the eluate were chromatographed on a Scherzo SM-C18 (3.0×150 mm, 3.0 μm) column with 20 mmol/L ammonium acetate containing 0.1% acetic acid-acetonitrile (97 : 3) as a mobile phase and were monitored at 261 nm. Quantification was performed by LC and LC-MS/MS. Calibration curves showed high linearity (correlation coefficient>0.998) between 1-25 μg/mL for LC and LC-MS/MS. Recoveries were 84-108% (CV≦5.8%) by HPLC and 79-105% (CV≦9.0%) by LC-MS/MS. The limit of quantitation for NA was 0.005-0.01 g/kg and that for NAA was 0.01-0.02 g/kg.

Nicotinic Acid Increases Adiponectin Secretion from Differentiated Bovine Preadipocytes through G-Protein Coupled Receptor Signaling

Directory of Open Access Journals (Sweden)

Christina Kopp

2014-11-01

Full Text Available The transition period in dairy cows (3 weeks prepartum until 3 weeks postpartum is associated with substantial mobilization of energy stores, which is often associated with metabolic diseases. Nicotinic acid (NA is an antilipolytic and lipid-lowering compound used to treat dyslipidaemia in humans, and it also reduces non-esterified fatty acids in cattle. In mice the G-protein coupled receptor 109A (GPR109A ligand NA positively affects the secretion of adiponectin, an important modulator of glucose and fat metabolism. In cattle, the corresponding data linking NA to adiponectin are missing. Our objective was to examine the effects of NA on adiponectin and AMPK protein abundance and the expression of mRNAs of related genes such as chemerin, an adipokine that enhances adiponectin secretion in vitro. Differentiated bovine adipocytes were incubated with pertussis toxin (PTX to verify the involvement of GPR signaling, and treated with 10 or 15 µM NA for 12 or 24 h. NA increased adiponectin concentrations (p ≤ 0.001 and the mRNA abundances of GPR109A (p ≤ 0.05 and chemerin (p ≤ 0.01. Pre-incubation with PTX reduced the adiponectin response to NA (p ≤ 0.001. The NA-stimulated secretion of adiponectin and the mRNA expression of chemerin in the bovine adipocytes were suggestive of GPR signaling-dependent improved insulin sensitivity and/or adipocyte metabolism in dairy cows.

REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

Science.gov (United States)

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

2015-01-01

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

Reinforcement enhancing effects of acute nicotine via electronic cigarettes.

Science.gov (United States)

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

2015-08-01

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

An investigation into the mechanisms of drug release from taste-masking fatty acid microspheres.

Science.gov (United States)

Qi, Sheng; Deutsch, David; Craig, Duncan Q M

2008-09-01

Fatty acid microspheres based on stearic and palmitic acids are known to form effective taste masking systems, although the mechanisms by which the drug is preferentially released in the lower gastrointestinal tract are not known. The objective of the present study was to identify the mechanisms involved, with a particular view to clarify the role of acid soap formation in the dissolution process. Microspheres were prepared by a spray chilling process. Using benzoic acid as a model drug and an alkaline dissolution medium, a faster drug release was observed in the mixed fatty acid formulation (50:50 stearic:palmitic acid (w/w)) compared to the single fatty acid component systems. Thermal and powder X-ray diffraction studies indicated a greater degree of acid soap formation for the mixed formulation in alkaline media compared to the single fatty acid systems. Particle size and porosity studies indicated a modest reduction in size for the mixed systems and an increase in porosity on immersion in the dissolution medium. It is proposed that the mixed fatty acid system form a mixed crystal system which in turn facilitates interaction with the dissolution medium, thereby leading to a greater propensity for acid soap formation which in turn forms a permeable liquid crystalline phase through which the drug may diffuse. The role of dissolution of palmitic acid into the dissolution medium is also discussed as a secondary mechanism.

Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates.

Science.gov (United States)

Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Morgan, Terry K; Rasanen, Juha P; Kroenke, Christopher D; Shoemaker, Sophie R; Spindel, Eliot R; Frias, Antonio E

2015-03-01

We previously demonstrated that prenatal nicotine exposure decreases neonatal pulmonary function in nonhuman primates, and maternal vitamin C supplementation attenuates these deleterious effects. However, the effect of nicotine on placental perfusion and development is not fully understood. This study utilizes noninvasive imaging techniques and histological analysis in a nonhuman primate model to test the hypothesis that prenatal nicotine exposure adversely effects placental hemodynamics and development but is ameliorated by vitamin C. Time-mated macaques (n = 27) were divided into 4 treatment groups: control (n = 5), nicotine only (n = 4), vitamin C only (n = 9), and nicotine plus vitamin C (n = 9). Nicotine animals received 2 mg/kg per day of nicotine bitartrate (approximately 0.7 mg/kg per day free nicotine levels in pregnant human smokers) from days 26 to 160 (term, 168 days). Vitamin C groups received ascorbic acid at 50, 100, or 250 mg/kg per day with or without nicotine. All underwent placental dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at 135-140 days and Doppler ultrasound at 155 days to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. Animals were delivered by cesarean delivery at 160 days. A novel DCE-MRI protocol was utilized to calculate placental perfusion from maternal spiral arteries. Placental tissue was processed for histopathology. Placental volume blood flow was significantly reduced in nicotine-only animals compared with controls and nicotine plus vitamin C groups (P = .03). Maternal placental blood flow was not different between experimental groups by DCE-MRI, ranging from 0.75 to 1.94 mL/mL per minute (P = .93). Placental histology showed increased numbers of villous cytotrophoblast cell islands (P vitamin C. Prenatal nicotine exposure significantly decreased fetal blood supply via reduced placental volume blood flow, which

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.

Cross-Linked Dependency of Boronic Acid-Conjugated Chitosan Nanoparticles by Diols for Sustained Insulin Release

Directory of Open Access Journals (Sweden)

Nabil A. Siddiqui

2016-10-01

Full Text Available Boronic acids have been widely investigated for their potential use as glucose sensors in glucose responsive polymeric insulin delivery systems. Interactions between cyclic diols and boronic acids, anchored to polymeric delivery systems, may result in swelling of the delivery system, releasing the drug. In this study, 4-formylphenylboronic acid conjugated chitosan was formulated into insulin containing nanoparticles via polyelectrolyte complexation. The nanoparticles had an average diameter of 140 ± 12.8 nm, polydispersity index of 0.17 ± 0.1, zeta potential of +19.1 ± 0.69 mV, encapsulation efficiency of 81% ± 1.2%, and an insulin loading capacity of 46% ± 1.8% w/w. Changes in size of the nanoparticles and release of insulin were type of sugar- and concentration-dependent. High concentration of diols resulted in a sustained release of insulin due to crosslink formation with boronic acid moieties within the nanoparticles. The formulation has potential to be developed into a self-regulated insulin delivery system for the treatment of diabetes.

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

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

Development of Poly Lactic/Glycolic Acid (PLGA Microspheres for Controlled Release of Rho-Associated Kinase Inhibitor

Directory of Open Access Journals (Sweden)

Sho Koda

2017-01-01

Full Text Available Purpose. The purpose of this study was to investigate the feasibility of poly lactic/glycolic acid (PLGA as a drug delivery carrier of Rho kinase (ROCK inhibitor for the treatment of corneal endothelial disease. Method. ROCK inhibitor Y-27632 and PLGA were dissolved in water with or without gelatin (W1, and a double emulsion [(W1/O/W2] was formed with dichloromethane (O and polyvinyl alcohol (W2. Drug release curve was obtained by evaluating the released Y-27632 by using high performance liquid chromatography. PLGA was injected into the anterior chamber or subconjunctiva in rabbit eyes, and ocular complication was evaluated by slitlamp microscope and histological analysis. Results. Y-27632 incorporated PLGA microspheres with different molecular weights, and different composition ratios of lactic acid and glycolic acid were fabricated. A high molecular weight and low content of glycolic acid produced a slower and longer release. The Y-27632 released from PLGA microspheres significantly promoted the cell proliferation of cultured corneal endothelial cells. The injection of PLGA did not induce any evident eye complication. Conclusions. ROCK inhibitor-incorporated PLGA microspheres were fabricated, and the microspheres achieved the sustained release of ROCK inhibitor over 7–10 days in vitro. Our data should encourage researchers to use PLGA microspheres for treating corneal endothelial diseases.

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

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...

Enantioselective changes in oxidative stress and toxin release in Microcystis aeruginosa exposed to chiral herbicide diclofop acid

Energy Technology Data Exchange (ETDEWEB)

Ye, Jing [School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418 (China); MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Natural Research and Environmental Sciences, Zhejiang University, Hangzhou 310058 (China); Zhang, Ying [Department of Environmental Science, East China Normal University, Shanghai 200241 (China); Chen, Shengwen [School of Urban Development and Environment Engineering, Shanghai Second Polytechnic University, Shanghai 201209 (China); Liu, Chaonan; Zhu, Yongqiang [School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418 (China); Liu, Weiping, E-mail: wliu@zju.edu.cn [MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Natural Research and Environmental Sciences, Zhejiang University, Hangzhou 310058 (China)

2014-01-15

Highlights: •The first study on enantioselective oxidative stress and toxin release from Microcystis aeruginosa. •Provide information for the R-enantiomer poses more oxidative stress than the S-enantiomer. •Lifecycle analysis of chiral pollutants needs more attention in environmental assessment. -- Abstract: Enantioselective oxidative stress and toxin release from Microcystis aeruginosa after exposure to the chiral herbicide diclofop acid were investigated. Racemic diclofop acid, R-diclofop acid and S-diclofop acid induced reactive oxygen species (ROS) generation, increased the concentration of malondialdehyde (MDA), enhanced the activity of superoxide dismutase (SOD) and triggered toxin release in M. aeruginosa to varying degrees. The increase in MDA concentration and SOD activity in M. aeruginosa occurred sooner after exposure to diclofop acid than when the cyanobacteria was exposed to either the R- and the S-enantiomer. In addition, enantioselective toxicity of the enantiomers was observed. The R-enantiomer trigged more ROS generation, more SOD activity and more toxin synthesis and release in M. aeruginosa cells than the S-enantiomer. Diclofop acid and its R-enantiomer may collapse the transmembrane proton gradient and destroy the cell membrane through lipid peroxidation and free radical oxidation, whereas the S-enantiomer did not demonstrate such action. R-diclofop acid inhibits the growth of M. aeruginosa in the early stage, but ultimately induced greater toxin release, which has a deleterious effect on the water column. These results indicate that more comprehensive study is needed to determine the environmental safety of the enantiomers, and application of chiral pesticides requires more direct supervision and training. Additionally, lifecycle analysis of chiral pollutants in aquatic system needs more attention to aide in the environmental assessment of chiral pesticides.

Acid stimulation (sour taste elicits GABA and serotonin release from mouse taste cells.

Directory of Open Access Journals (Sweden)

Yijen A Huang

Full Text Available Several transmitter candidates including serotonin (5-HT, ATP, and norepinephrine (NE have been identified in taste buds. Recently, γ-aminobutyric acid (GABA as well as the associated synthetic enzymes and receptors have also been identified in taste cells. GABA reduces taste-evoked ATP secretion from Receptor cells and is considered to be an inhibitory transmitter in taste buds. However, to date, the identity of GABAergic taste cells and the specific stimulus for GABA release are not well understood. In the present study, we used genetically-engineered Chinese hamster ovary (CHO cells stably co-expressing GABA(B receptors and Gαqo5 proteins to measure GABA release from isolated taste buds. We recorded robust responses from GABA biosensors when they were positioned against taste buds isolated from mouse circumvallate papillae and the buds were depolarized with KCl or a stimulated with an acid (sour taste. In contrast, a mixture of sweet and bitter taste stimuli did not trigger GABA release. KCl- or acid-evoked GABA secretion from taste buds was Ca(2+-dependent; removing Ca(2+ from the bathing medium eliminated GABA secretion. Finally, we isolated individual taste cells to identify the origin of GABA secretion. GABA was released only from Presynaptic (Type III cells and not from Receptor (Type II cells. Previously, we reported that 5-HT released from Presynaptic cells inhibits taste-evoked ATP secretion. Combined with the recent findings that GABA depresses taste-evoked ATP secretion, the present results indicate that GABA and 5-HT are inhibitory transmitters in mouse taste buds and both likely play an important role in modulating taste responses.

Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors

DEFF Research Database (Denmark)

Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E.

2015-01-01

Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium......-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L...... to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms....

Effect of nicotine on negative affect among more impulsive smokers.

Science.gov (United States)

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

2006-08-01

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

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

Science.gov (United States)

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

2006-10-01

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

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

International Nuclear Information System (INIS)

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

1985-01-01

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

Effects of low molecular weight organic acids on 137Cs release from contaminated soils

International Nuclear Information System (INIS)

Chiang, Po Neng; Wang, Ming Kuang; Huang, Pan Ming; Wang, Jeng Jong

2011-01-01

Radio pollutant removal is one of several priority restoration strategies for the environment. This study assessed the effect of low molecular weight organic acid on the lability and mechanisms for release of 137 Cs from contaminated soils. The amount of 137 Cs radioactivity released from contaminated soils reacting with 0.02 M low molecular weight organic acids (LMWOAs) specifically acetic, succinic, oxalic, tartaric, and citric acid over 48 h were 265, 370, 760, 850, and 1002 Bq kg -1 , respectively. The kinetic results indicate that 137 Cs exhibits a two-step parabolic diffusion equation and a good linear relationship, indicating that the parabolic diffusion equation describes the data quite well, as shown by low p and high r 2 values. The fast stage, which was found to occur within a short period of time (0.083-3 h), corresponds to the interaction of LMWOAs with the surface of clay minerals; meanwhile, during the slow stage, which occurs over a much longer time period (3-24 h), desorption primarily is attributed to inter-particle or intra-particle diffusion. After a fifth renewal of the LMWOAs, the total levels of 137 Cs radioactivity released by acetic, succinic, oxalic, tartaric, and citric acid were equivalent to 390, 520, 3949, 2061, and 4422 Bq kg -1 soil, respectively. H + can protonate the hydroxyl groups and oxygen atoms at the broken edges or surfaces of the minerals, thereby weakening Fe-O and Al-O bonds. After protonation of H + , organic ligands can attack the OH and OH 2 groups in the minerals easily, to form complexes with surface structure cations, such as Al and Fe. The amounts of 137 Cs released from contaminated soil treated with LMWOAs were substantially increased, indicating that the LMWOAs excreted by the roots of plants play a critical role in 137 Cs release.

Nicotine Reduction Revisited: Science and Future Directions

Science.gov (United States)

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

2015-01-01

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

Nicotine Analysis in Several Non-Tobacco Plant Materials

Directory of Open Access Journals (Sweden)

Moldoveanu Serban C.

2016-04-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-07-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors.

NARCIS (Netherlands)

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

2015-01-01

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

Adsorption and release of amino acids mixture onto apatitic calcium phosphates analogous to bone mineral

Science.gov (United States)

El Rhilassi, A.; Mourabet, M.; El Boujaady, H.; Bennani-Ziatni, M.; Hamri, R. El; Taitai, A.

2012-10-01

Study focused on the interaction of adsorbate with poorly crystalline apatitic calcium phosphates analogous to bone mineral. Calcium phosphates prepared in water-ethanol medium at physiological temperature (37 °C) and neutral pH, their Ca/P ratio was between 1.33 and 1.67. Adsorbate used in this paper takes the mixture form of two essential amino acids L-lysine and DL-leucine which have respectively a character hydrophilic and hydrophobic. Adsorption and release are investigated experimentally; they are dependent on the phosphate type and on the nature of adsorbate L-lysine, DL-leucine and their mixture. Adsorption of mixture of amino acids on the apatitic calcium phosphates is influenced by the competition between the two amino acids: L-lysine and DL-leucine which exist in the medium reaction. The adsorption kinetics is very fast while the release kinetics is slow. The chemical composition of apatite has an influence on both adsorption and release. The interactions adsorbate-adsorbent are electrostatic type. Adsorption and release reactions of the amino acid mixture are explained by the existence of the hydrated surface layer of calcium phosphate apatite. The charged sbnd COOsbnd and sbnd NH3+ of adsorbates are the strongest groups that interact with the surface of apatites, the adsorption is mainly due to the electrostatic interaction between the groups sbnd COOsbnd of amino acids and calcium Ca2+ ions of the apatite. Comparative study of interactions between adsorbates (L-lysine, DL-leucine and their mixture) and apatitic calcium phosphates is carried out in vitro by using UV-vis and infrared spectroscopy IR techniques.

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

Science.gov (United States)

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

Effects of Ascorbic Acid on Reproductive Functions of Male Wistar ...

African Journals Online (AJOL)

In conclusion, ascorbic acid supplement may suppress nicotine toxic effects on reproductive functions in male rats. ... et al., 2007). Nicotine is rapidly absorbed by the brain .... difference (LSD) test. p<0.05 was considered significant. Statistical ...

The effect of endogenous essential and nonessential fatty acids on the uptake and subsequent agonist-induced release of arachidonate

International Nuclear Information System (INIS)

Furth, E.E.; Hurtubise, V.; Schott, M.A.; Laposata, M.

1989-01-01

We have demonstrated that the uptake and agonist-induced release of a pulse of arachidonate are influenced by the size and composition of preexisting endogenous fatty acid pools. EFD-1 cells, an essential fatty acid-deficient mouse fibrosarcoma cell line, were incubated with radiolabeled (14C or 3H) arachidonate, linoleate, eicosapentaenoate (EPA), palmitate, or oleate in concentrations of 0-33 microM for 24 h. After 24 h, the cells were pulsed with 0.67 microM radiolabeled (3H or 14C, opposite first label) arachidonate for 15 min and then stimulated with 10 microM bradykinin for 4 min. Because EFD-1 cells contain no endogenous essential fatty acids, we were able to create essential fatty acid-repleted cells for which the specific activity of the newly constructed endogenous essential fatty acid pool was known. Loading the endogenous pool with the essential fatty acids arachidonate, eicosapentaenoate, or linoleate (15-20 nmol of fatty acid incorporated/10(6) cells) decreased the uptake of a pulse of arachidonate from 200 to 100 pmol/10(6) cells but had no effect on palmitate uptake. The percent of arachidonate incorporated during the pulse which was released upon agonist stimulation increased 2-fold (4-8%) as the endogenous pool of essential fatty acids was increased from 0 to 15-20 nmol/10(6) cells. This 8% release was at least 3-fold greater than the percent release from the various endogenous essential fatty acid pools. In contrast, loading the endogenous pool with the nonessential fatty acids oleate or palmitate to more than 2-3 times their preexisting cellular level had no effect on the uptake of an arachidonate pulse. Like the essential fatty acids, increasing endogenous oleate increased (by 2-fold) the percent release of arachidonate incorporated during the pulse, whereas endogenous palmitate had no effect on subsequent agonist-induced release from this arachidonate pool

Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release.

Science.gov (United States)

Chu, David S H; Johnson, Russell N; Pun, Suzie H

2012-02-10

Degradable cationic polymers are desirable for in vivo nucleic acid delivery because they offer significantly decreased toxicity over non-degradable counterparts. Peptide linkers provide chemical stability and high specificity for particular endopeptidases but have not been extensively studied for nucleic acid delivery applications. In this work, enzymatically degradable peptide-HPMA copolymers were synthesized by RAFT polymerization of HPMA with methacrylamido-terminated peptide macromonomers, resulting in polymers with low polydispersity and near quantitative incorporation of peptides. Three peptide-HPMA copolymers were evaluated: (i) pHCathK(10), containing peptides composed of the linker phe-lys-phe-leu (FKFL), a substrate of the endosomal/lysosomal endopeptidase cathepsin B, connected to oligo-(L)-lysine for nucleic acid binding, (ii) pHCath(D)K(10), containing the FKFL linker with oligo-(D)-lysine, and (iii) pH(D)Cath(D)K(10), containing all (D) amino acids. Cathepsin B degraded copolymers pHCathK(10) and pHCath(D)K(10) within 1 h while no degradation of pH(D)Cath(D)K(10) was observed. Polyplexes formed with pHCathK(10) copolymers show DNA release by 4 h of treatment with cathepsin B; comparatively, polyplexes formed with pHCath(D)K(10) and pH(D)Cath(D)K(10) show no DNA release within 8 h. Transfection efficiency in HeLa and NIH/3T3 cells were comparable between the copolymers but pHCathK(10) was less toxic. This work demonstrates the successful application of peptide linkers for degradable cationic polymers and DNA release. Copyright © 2011 Elsevier B.V. All rights reserved.

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: ...

Counterfeit Electronic Cigarette Products with Mislabeled Nicotine Concentrations.

Science.gov (United States)

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

2017-07-01

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

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

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

African Journals Online (AJOL)

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

Antifungal activity of nicotine and its cadmium complex

International Nuclear Information System (INIS)

Zaidi, I.M.; Gul, A.

2005-01-01

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