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Sample records for aerobic nicotinic acid

  1. Renal transport and metabolism of nicotinic acid

    International Nuclear Information System (INIS)

    Schuette, S.; Rose, R.C.

    1986-01-01

    Renal metabolism and brush-border transport of nicotinic acid were studied in renal cortical slices and brush-border membrane vesicles exposed to a physiological concentration of vitamin (2.2-3.5 microM). Vesicle transport of [ 3 H]nicotinic acid was found to be Na+ dependent and concentrative. The presence of a Na+ gradient resulted in a fivefold increase in the rate of nicotinic acid uptake over that observed with mannitol and caused a transient nicotinic acid accumulation two- to fourfold above the equilibrium value. The effects of membrane potential, pH, and elimination of Na+-H+ exchange were also studied. Cortical slices and isolated tubules exposed to 2.2 microM [ 14 C]nicotinic acid took up vitamin and rapidly metabolized most of it to intermediates in the Preiss-Handler pathway for NAD biosynthesis; little free nicotinic acid was detectable intracellularly. The replacement of Na+ with Li+ in the bathing medium reduced total accumulation of 14 C label primarily as a result of reduced nicotinic acid uptake. Cortical tissue concentrated free nicotinic acid only when the involved metabolic pathways were saturated by levels of nicotinic acid far in excess of what occurs in vivo

  2. Compound list: nicotinic acid [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available nicotinic acid NIC 00081 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/nicotinic_aci...d.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/nicotinic_aci.../in_vivo/Liver/Single/nicotinic_acid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc...iencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/nicotinic_acid.Rat.in_vivo.Liver.Repeat.zip ...

  3. Nicotinic and iso nicotinic acids: interactions with gamma radiation and acid-base equilibrium

    International Nuclear Information System (INIS)

    Ribeiro, Z.A.

    1984-01-01

    The values of pKa 1 and pKa 2 for nicotinic and iso nicotinic acids in aqueous medium were determined. The effects of gamma radiation about these acids by infrared and ultraviolet spectrophotometry and thermal gravimetric analysis were also studied. It was verified that the radiolysis of acids occurred by the two process of first order, determining the degradation constant and the degradation factors for each one of the solutions. (C.G.C.)

  4. 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

  5. Aerobic Microbial Degradation of Glucoisosaccharinic Acid

    OpenAIRE

    Strand, S. E.; Dykes, J.; Chiang, V.

    1984-01-01

    α-Glucoisosaccharinic acid (GISA), a major by-product of kraft paper manufacture, was synthesized from lactose and used as the carbon source for microbial media. Ten strains of aerobic bacteria capable of growth on GISA were isolated from kraft pulp mill environments. The highest growth yields were obtained with Ancylobacter spp. at pH 7.2 to 9.5. GISA was completely degraded by cultures of an Ancylobacter isolate. Ancylobacter cell suspensions consumed oxygen and produced carbon dioxide in r...

  6. Aerobic microbial degradation of glucoisosaccharinic Acid.

    Science.gov (United States)

    Strand, S E; Dykes, J; Chiang, V

    1984-02-01

    alpha-Glucoisosaccharinic acid (GISA), a major by-product of kraft paper manufacture, was synthesized from lactose and used as the carbon source for microbial media. Ten strains of aerobic bacteria capable of growth on GISA were isolated from kraft pulp mill environments. The highest growth yields were obtained with Ancylobacter spp. at pH 7.2 to 9.5. GISA was completely degraded by cultures of an Ancylobacter isolate. Ancylobacter cell suspensions consumed oxygen and produced carbon dioxide in response to GISA addition. A total of 22 laboratory strains of bacteria were tested, and none was capable of growth on GISA. GISA-degrading isolates were not found in forest soils.

  7. Thermal behaviour of nicotinic acid, sodium nicotinate and its compounds with some bivalent transition metal ions

    International Nuclear Information System (INIS)

    Nascimento, A.L.C.S. do; Caires, F.J.; Gomes, D.J.C.; Gigante, A.C.; Ionashiro, M.

    2014-01-01

    Graphical abstract: - Highlights: • The transition metal ion nicotinates were synthesized. • The TG–DTA curves provided previously unreported information about thermal behaviour. • The gaseous products released were detected by TG–DSC coupled to FTIR. - Abstract: Solid-state M(L) 2 ·nH 2 O compounds, where M stands for bivalent transition metals (Mn, Fe, Co, Ni, Cu and Zn), L is nicotinate and n = 0–4.5, have been synthesized. Characterization and thermal behaviour of these compounds were investigated employing elemental analysis based on the mass losses observed in the TG–DTA curves, complexometry, X-ray diffractometry, infrared spectroscopy (FTIR), simultaneous thermogravimetric and differential thermal analysis (TG–DTA) and TG–DSC coupled to FTIR. The thermal behaviour of nicotinic acid and its sodium salt was also investigated. For the hydrated transition metal compounds, the dehydration and thermal decomposition of the anhydrous compounds occur in a single step. For the sodium nicotinate, the final residue up to 765 °C is sodium carbonate and for the transition metal nicotinates, the final residues are Mn 3 O 4 , Fe 2 O 3 , Co 3 O 4 , NiO, CuO and ZnO. The results also provided information concerning the thermal stability, thermal decomposition and identification of the gaseous products evolved during the thermal decomposition of the compounds

  8. 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.

  9. Comparison of the formation of nicotinic acid conjugates in leaves of different plant species.

    Science.gov (United States)

    Ashihara, Hiroshi; Yin, Yuling; Katahira, Riko; Watanabe, Shin; Mimura, Tetsuro; Sasamoto, Hamako

    2012-11-01

    There are three metabolic fates of nicotinic acid in plants: (1) nicotinic acid mononucleotide formation for NAD synthesis by the so-called salvage pathway of pyridine nucleotide biosynthesis; (2) nicotinic acid N-glucoside formation; and (3) trigonelline (N-methylnicotinic acid) formation. In the present study, the metabolism of [carbonyl-(14)C]nicotinamide was investigated in leaves of 23 wild plant species. All species readily converted nicotinamide to nicotinic acid, and only a fraction of nicotinic acid was utilised for NAD and NADP synthesis. The remaining nicotinic acid is converted to the nicotinic acid conjugates. Only one plant species, Cycas revoluta, produced both nicotinic acid N-glucoside and trigonelline; the other 22 species produced one or other of the conjugates. The nicotinic acid N-glucoside-forming plants are Cyathea lepifera, Arenga trewmula var. englri, Barringtonia racemosa, Ilex paraguariensis, Angelica japonica, Scaevola taccada and Farfugium japonicum. In contrast, trigonelline is formed in C. lepifera, Ginkgo biloba, Pinus luchuensis, Casuarina equisetifolia, Alocasia odora, Pandanus odoratissimus, Hylocereus undatus, Kalanchoe pinnata, Kalanchoe tubiflora, Populus alba, Garcinia subelliptica, Oxalis corymbosa, Leucaena leucocephala, Vigna marina, Hibiscus tiliaceus and Melicope triphylla. The diversity of nicotinic acid conjugate formation in plants is discussed using these results and our previous investigation involving a few model plants, various crops and ferns. Nicotinic acid N-glucoside formation was restricted mostly to ferns and selected orders of angiosperms, whereas other plants produce trigonelline. In most cases the formation of both nicotinic acid conjugates is incompatible, but some exceptions have been found. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. 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

  11. Gamma-aminobutyric acid mediates nicotine biosynthesis in tobacco under flooding stress

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    2016-02-01

    Full Text Available Gamma-aminobutyric acid (GABA is a four-carbon non-protein amino acid conserved from bacteria to plants and vertebrates. Increasing evidence supports a regulatory role for GABA in plant development and the plant's response to environmental stress. The biosynthesis of nicotine, the main economically important metabolite in tobacco, is tightly regulated. GABA has not hitherto been reported to function in nicotine biosynthesis. Here we report that water flooding treatment (hypoxia markedly induced the accumulation of GABA and stimulated nicotine biosynthesis. Suppressing GABA accumulation by treatment with glutamate decarboxylase inhibitor impaired flooding-induced nicotine biosynthesis, while exogenous GABA application directly induced nicotine biosynthesis. Based on these results, we propose that GABA triggers nicotine biosynthesis in tobacco seedlings subjected to flooding. Our results provide insight into the molecular mechanism of nicotine biosynthesis in tobacco plants exposed to environmental stress.

  12. 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.

  13. 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.

  14. 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

  15. Synthesis, coordination and structure of pentacoordinated oxovanadium(IV) complexes of hippuric and nicotinic acids

    International Nuclear Information System (INIS)

    Kumar, G.; Singh, Ranjana; Singh, N.P.

    1981-01-01

    Pentacoordinated oxovanadium(IV) complexes formed with hippuric acid (VOL 2 ) and nicotinic acid ((VO) 2 L 2 (OH) 2 ) 5 H 2 O have been synthesized and their structures investigated by magnetochemical and spectra (i.r., U.V. and reflectance) measurements. The I.R. studies indicate that in the bis-hippurato complex the carboxylate group itself acts as a bidentate chelating group, whereas, with nicotinic acid, coordination occurs through both the pyridine N and COO - group. Electronic spectra show them to have pentacoordinated structures. Magnetic studies suggest that the complex formed with nicotinic acid possibly has a binuclear structure with subnormal magnetic moment. (author)

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  17. [Nicotinic acid increases cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia].

    Science.gov (United States)

    Figueroa, Catalina; Droppelmann, Katherine; Quiñones, Verónica; Amigo, Ludwig; Mendoza, Camila; Serrano, Valentina; Véjar, Margarita; Maiz, Alberto; Rigotti, Attilio

    2015-09-01

    Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown. To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients. In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI. Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells. Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.

  18. 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.

  19. 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.

  20. 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

  1. Uptake and distribution of 14C-nicotinic acid in barley seeds and seedlings

    International Nuclear Information System (INIS)

    Bernhardt, D.; Bandzhyulene, R.S.; Mateikene, I.K.; Ozheraitene, M.V.; Shimkunas, R.A.; Bluzmanas, P.I.

    1991-01-01

    The authors investigated uptake and distribution of 14 C-nicotinic acid in seeds and seedlings of barley (Hordeum vulgare L.). It is established that nicotinic acid can enter barley plants in different ways depending upon the method of treatment, being capable of entering both dry seeds (through the endosperm) and seedlings (through roots and leaves equally well). Distribution of this acid throughout the plant was practically the same regardless of the method of introduction and was characterized by weak entry into stem growing points, absence of translocation into leaves with completed growth, and accumulation in young leaves. It may be hypothesized that nicotinic acid entering growing leaves is intensively converted to other compounds. However, the conversion products do not lose their mobility, since the radioactive label is detected in reproductive organs at the end of vegetation

  2. 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.

  3. 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.)

  4. The nicotinic acid balance in patients with syringomyelia in the course of deep X-ray therapy

    International Nuclear Information System (INIS)

    Oganesyan, A.A.

    1975-01-01

    Patients with syringomyelia showed a lowered nicotinic acid content, which deficit increased with deep x-ray therapy. Differences in the total dose of penetrating radiation did not seem to affect the providing of nicotinic acid to the patients' organism. (V.A.P.)

  5. Activity of nicotinic acid substituted nicotinic acid adenine dinucleotide phosphate (NAADP) analogs in a human cell line: difference in specificity between human and sea urchin NAADP receptors.

    Science.gov (United States)

    Ali, Ramadan A; Zhelay, Tetyana; Trabbic, Christopher J; Walseth, Timothy F; Slama, James T; Giovannucci, David R; Wall, Katherine A

    2014-02-01

    Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca2+ mobilizing second messenger that has been identified. We have previously shown that NAADP analogs substituted at the 5-position of nicotinic acid were recognized by the sea urchin receptor at low concentration, whereas the 4- substituted analogs were not as potent. However, to date the structure-activity relationship (SAR) of these analogs has not been addressed in mammalian systems. Thus, we asked whether these structurally modified analogs behave similarly in an NAADP-responsive mammalian cell line (SKBR3) using microinjection and single cell fluorescent imaging methods. Novel "caged" 4- and 5-substituted NAADP analogs that were activated inside the cell by flash photolysis resulted in Ca2+ mobilizing activity in SKBR3 cells in a concentration dependent manner, but with reduced effectiveness compared to unmodified NAADP. The SAR in mammalian SKBR3 cells was quite different from that of sea urchin and may suggest that there are differences between NAADP receptors in different species or tissues. Importantly, these data indicate that modifications at the 4- and 5-position of the nicotinic acid ring may lead to the development of functional photoaffinity labels that could be used for receptor localization and isolation in mammalian systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Nicotinamide Riboside and Nicotinic Acid Riboside Salvage in Fungi and Mammals

    Science.gov (United States)

    Belenky, Peter; Christensen, Kathryn C.; Gazzaniga, Francesca; Pletnev, Alexandre A.; Brenner, Charles

    2009-01-01

    NAD+ is a co-enzyme for hydride transfer enzymes and an essential substrate of ADP-ribose transfer enzymes and sirtuins, the type III protein lysine deacetylases related to yeast Sir2. Supplementation of yeast cells with nicotinamide riboside extends replicative lifespan and increases Sir2-dependent gene silencing by virtue of increasing net NAD+ synthesis. Nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiated by splitting the nucleoside into a nicotinamide base followed by nicotinamide salvage. Genetic evidence has established that uridine hydrolase, purine nucleoside phosphorylase, and methylthioadenosine phosphorylase are required for Nrk-independent utilization of nicotinamide riboside in yeast. Here we show that mammalian purine nucleoside phosphorylase but not methylthioadenosine phosphorylase is responsible for mammalian nicotinamide riboside kinase-independent nicotinamide riboside utilization. We demonstrate that so-called uridine hydrolase is 100-fold more active as a nicotinamide riboside hydrolase than as a uridine hydrolase and that uridine hydrolase and mammalian purine nucleoside phosphorylase cleave nicotinic acid riboside, whereas the yeast phosphorylase has little activity on nicotinic acid riboside. Finally, we show that yeast nicotinic acid riboside utilization largely depends on uridine hydrolase and nicotinamide riboside kinase and that nicotinic acid riboside bioavailability is increased by ester modification. PMID:19001417

  7. Interaction Effect of 8-Week Aerobic Exercise and Omega-3 Fatty Acid

    OpenAIRE

    Gholamreza Khedri; Mehdi Mogharnasi

    2013-01-01

    Background: Scientific evidence indicates the impact of aerobic exercise and omega-3 fatty acids - both –are for the improvement of the cardiovascular system .The purpose of this research was about studies interaction effect of 8 weeks aerobic exercise and omega- 3 fatty acids supplementation on plasma adiponectin concentration of elderly men.Materials and Methods: In this study, 36 male non-athletes aged were between 50 to 70 year age range of men aged the city of Genaveh. Statistical sample...

  8. Acetic acid production from food wastes using yeast and acetic acid bacteria micro-aerobic fermentation.

    Science.gov (United States)

    Li, Yang; He, Dongwei; Niu, Dongjie; Zhao, Youcai

    2015-05-01

    In this study, yeast and acetic acid bacteria strains were adopted to enhance the ethanol-type fermentation resulting to a volatile fatty acids yield of 30.22 g/L, and improve acetic acid production to 25.88 g/L, with food wastes as substrate. In contrast, only 12.81 g/L acetic acid can be obtained in the absence of strains. The parameters such as pH, oxidation reduction potential and volatile fatty acids were tested and the microbial diversity of different strains and activity of hydrolytic ferment were investigated to reveal the mechanism. The optimum pH and oxidation reduction potential for the acetic acid production were determined to be at 3.0-3.5 and -500 mV, respectively. Yeast can convert organic matters into ethanol, which is used by acetic acid bacteria to convert the organic wastes into acetic acid. The acetic acid thus obtained from food wastes micro-aerobic fermentation liquid could be extracted by distillation to get high-pure acetic acid.

  9. 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%.

  10. 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

  11. Identification of Isn1 and Sdt1 as Glucose- and Vitamin-regulated Nicotinamide Mononucleotide and Nicotinic Acid Mononucleotide 5′-Nucleotidases Responsible for Production of Nicotinamide Riboside and Nicotinic Acid Riboside*

    OpenAIRE

    Bogan, Katrina L.; Evans, Charles; Belenky, Peter; Song, Peng; Burant, Charles F.; Kennedy, Robert; Brenner, Charles

    2009-01-01

    Recently, we discovered that nicotinamide riboside and nicotinic acid riboside are biosynthetic precursors of NAD+, which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide riboside and nicotinic acid riboside are authentic intracellular metabolites in yeast...

  12. 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.

  13. Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats.

    Science.gov (United States)

    Ateyya, Hayam; Nader, Manar A; Attia, Ghalia M; El-Sherbeeny, Nagla A

    2017-05-01

    Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.

  14. 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.

  15. 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.

  16. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition.

    Science.gov (United States)

    Bogan, Katrina L; Brenner, Charles

    2008-01-01

    Although baseline requirements for nicotinamide adenine dinucleotide (NAD+) synthesis can be met either with dietary tryptophan or with less than 20 mg of daily niacin, which consists of nicotinic acid and/or nicotinamide, there is growing evidence that substantially greater rates of NAD+ synthesis may be beneficial to protect against neurological degeneration, Candida glabrata infection, and possibly to enhance reverse cholesterol transport. The distinct and tissue-specific biosynthetic and/or ligand activities of tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD+ precursor, nicotinamide riboside, reviewed herein, are responsible for vitamin-specific effects and side effects. Because current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation and propose areas for future research.

  17. Synthesis and characterization of divalent manganese, cobalt, nickel, copper and zinc complexes with nicotinic acid

    Science.gov (United States)

    Singh, Raghuvir; Rao, R. S. Sreenivas

    1981-02-01

    Coordination compounds of the transition metal(II) acetylacetonates of the formula [M(NA) 2(acac) 2 ] n (M = Mn, Co, Ni, Cu and Zn; NA = nicotinic acid and acac = acetyl-acetonate anion) have been synthesized and characterized by chemical analysis, magnetic susceptibility, ligand-field spectra, IR and far-IR spectral measurements as well as photoacoustic spectroscopy in the solid state. Tentative stereochemistries for the complexes isolated in the solid state are suggested. The ligand-field parameters 10 Dq, B, β, λ and CFSE are calculated for cobalt and nickel complexes and are in good agreement with the proposed geometries. The metal ions attain six-coordination through the four oxygens of the anion and two donor atoms of the nicotinic acid ligands acting always as monodentate ligands. The formation of the compound results in a considerable shift of v(M-O) to lower frequencies in all the compounds related to parent acetylacetonates.

  18. Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells*

    Science.gov (United States)

    Kulikova, Veronika; Shabalin, Konstantin; Nerinovski, Kirill; Dölle, Christian; Niere, Marc; Yakimov, Alexander; Redpath, Philip; Khodorkovskiy, Mikhail; Migaud, Marie E.; Ziegler, Mathias; Nikiforov, Andrey

    2015-01-01

    NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5′-nucleotidases (5′-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5′-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5′-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors. PMID:26385918

  19. Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells.

    Science.gov (United States)

    Kulikova, Veronika; Shabalin, Konstantin; Nerinovski, Kirill; Dölle, Christian; Niere, Marc; Yakimov, Alexander; Redpath, Philip; Khodorkovskiy, Mikhail; Migaud, Marie E; Ziegler, Mathias; Nikiforov, Andrey

    2015-11-06

    NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5'-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5'-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. 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.)

  1. 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.

  2. THE EFFECTS OF INOCULANT LACTIC ACID BACTERIA ON THE FERMENTATION AND AEROBIC STABILITY OF SUNFLOWER SILAGE

    Directory of Open Access Journals (Sweden)

    Fisun Koc

    2009-12-01

    Full Text Available This study was carried out to determine the effects of actic acid bacterial inoculant on the fermentation and aerobic stability of sunflower silages. Sunflower was harvested at the milk stage. Inoculant-1174 (Pioneer®,USA was used as homofermentative lactic acid bacterial inoculant. Inoculant was applied 6.00 log10 cfu/g silage levels. Silages with no additive served as controls. After treatment, the chopped sunflower was ensiled in the PVC type laboratory silos. Three silos for each group were sampled for chemical and microbiological analysis on days 2, 4, 7, 14, 21, 28 and 56 after ensiling. At the end of the ensiling period, all silages were subjected to an aerobic stability test for 14 days. Neither inoculant improved the fermentation parameters of sunflower silages. At the end of the ensiling period, inoculant increased lactic acid bacteria (LAB and decreased yeast and mould numbers of silages. Inoculant treatment did not affect aerobic stability of silages.

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

    Directory of Open Access Journals (Sweden)

    Santanu Kar Mahapatra

    2011-01-01

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

  4. 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

  5. Simultaneous saccharification and aerobic fermentation of high titer cellulosic citric acid by filamentous fungus Aspergillus niger.

    Science.gov (United States)

    Hou, Weiliang; Bao, Jie

    2018-04-01

    Simultaneous saccharification and fermentation (SSF) is the most efficient operation in biorefining conversion, but aerobic SSF under high solids loading significantly faces the serious oxygen transfer limitation. This study took the first insight into an aerobic SSF by high oxygen demanding filamentous fungi in highly viscous lignocellulose hydrolysate. The results show that oxygen requirement in the aerobic SSF by Aspergillus niger was well satisfied for production of cellulosic citric acid. The record high citric acid titer of 136.3 g/L and the overall conversion yield of 74.9% of cellulose were obtained by the aerobic SSF. The advantage of SSF to the separate hydrolysis and fermentation (SHF) on citric acid fermentation was compared based on the rigorous Aspen Plus modeling. The techno-economic analysis indicates that the minimum citric acid selling price (MCSP) of $0.603 per kilogram by SSF was highly competitive with the commercial citric acid from starch feedstock. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Enhancing post aerobic digestion of full-scale anaerobically digested sludge using free nitrous acid pretreatment.

    Science.gov (United States)

    Wang, Qilin; Zhou, Xu; Peng, Lai; Wang, Dongbo; Xie, Guo-Jun; Yuan, Zhiguo

    2016-05-01

    Post aerobic digestion of anaerobically digested sludge (ADS) has been extensively applied to the wastewater treatment plants to enhance sludge reduction. However, the degradation of ADS in the post aerobic digester itself is still limited. In this work, an innovative free nitrous acid (HNO2 or FNA)-based pretreatment approach is proposed to improve full-scale ADS degradation in post aerobic digester. The post aerobic digestion was conducted by using an activated sludge to aerobically digest ADS for 4 days. Degradations of the FNA-treated (treated at 1.0 and 2.0 mg N/L for 24 h) and untreated ADSs were then determined and compared. The ADS was degraded by 26% and 32%, respectively, in the 4-day post aerobic digestion period while being pretreated at 1.0 and 2.0 mg HNO2-N/L. In comparison, only 20% of the untreated ADS was degraded. Economic analysis demonstrated that the implementation of FNA pretreatment can be economically favourable or not depending on the sludge transport and disposal cost. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Identification of Isn1 and Sdt1 as Glucose- and Vitamin-regulated Nicotinamide Mononucleotide and Nicotinic Acid Mononucleotide 5′-Nucleotidases Responsible for Production of Nicotinamide Riboside and Nicotinic Acid Riboside*

    Science.gov (United States)

    Bogan, Katrina L.; Evans, Charles; Belenky, Peter; Song, Peng; Burant, Charles F.; Kennedy, Robert; Brenner, Charles

    2009-01-01

    Recently, we discovered that nicotinamide riboside and nicotinic acid riboside are biosynthetic precursors of NAD+, which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide riboside and nicotinic acid riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide riboside was detected with a biological assay, and intracellular levels of nicotinamide riboside, nicotinic acid riboside, and other NAD+ metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5′-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide riboside and nicotinic acid riboside in cells. Isn1, initially classified as an IMP-specific 5′-nucleotidase, and Sdt1, initially classified as a pyrimidine 5′-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD+. Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD+ metabolism. PMID:19846558

  8. Identification of Isn1 and Sdt1 as glucose- and vitamin-regulated nicotinamide mononucleotide and nicotinic acid mononucleotide [corrected] 5'-nucleotidases responsible for production of nicotinamide riboside and nicotinic acid riboside.

    Science.gov (United States)

    Bogan, Katrina L; Evans, Charles; Belenky, Peter; Song, Peng; Burant, Charles F; Kennedy, Robert; Brenner, Charles

    2009-12-11

    Recently, we discovered that nicotinamide riboside and nicotinic acid riboside are biosynthetic precursors of NAD(+), which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide riboside and nicotinic acid riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide riboside was detected with a biological assay, and intracellular levels of nicotinamide riboside, nicotinic acid riboside, and other NAD(+) metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5'-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide riboside and nicotinic acid riboside in cells. Isn1, initially classified as an IMP-specific 5'-nucleotidase, and Sdt1, initially classified as a pyrimidine 5'-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD(+). Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD(+) metabolism.

  9. Acetic Acid Formation by Selective Aerobic Oxidation of Aqueous Ethanol over Heterogeneous Ruthenium Catalysts

    DEFF Research Database (Denmark)

    Gorbanev, Yury; Kegnæs, Søren; Hanning, Christopher William

    2012-01-01

    Heterogeneous catalyst systems comprising ruthenium hydroxide supported on different carrier materials, titania, alumina, ceria, and spinel (MgAl2O4), were applied in selective aerobic oxidation ethanol to form acetic acid, an important bulk chemical and food ingredient. The catalysts were charac...

  10. Absorption of thiamine and nicotinic acid in the rat intestine during fasting and immobilization stress

    Science.gov (United States)

    Kirilyuk, O. G.; Khmelevskiy, Y. V.

    1980-01-01

    By perfusion of isolated sections of intestine with a solution containing thiamine at a concentration of 3.1 micromole, it was established that thiamine absorption in animals fasted for 72 hours decreased by 28 percent, whereas absorption increased by 12 percent in rats after 24 hour immobilization. After immobilization, absorption of label in the intestinal mucosa increased. Na K ATPase activity in the intestinal mucosa decreased by 10 percent during fasting, and it increased with immobilization of the animals. Activity of Na K ATPase in the intestinal mucosa cells determined the absorption rate of thiamine and nicotinic acid at the level of vitamin transport through the plasma membranes of the enterocytes.

  11. Optimization of vanadium oxide catalyst for the oxidation of 3-methylpyridine into nicotinic acid

    Directory of Open Access Journals (Sweden)

    Vorobyev Pavel

    2017-01-01

    Full Text Available Upon modification of V2O5 with SnO2 or ZrO2, increase in the activity and selectivity of the vanadium-oxide catalyst in the vapor-phase oxidation of 3-methylpyridine into nicotinic acid were observed. It was shown that the promoting effects of SnO2 and ZrO2 were the result of increases under their influence of the proton affinity of the vanadyl oxygen and decreases in the enthalpy of deprotonation of the methyl group of the substrate, connected by a nitrogen atom with the Lewis acidic center (vanadium ion. The given characteristics were calculated by the density functional theory quantum-chemical method. Modification of binary V2O5–SnO2 and V2O5–ZrO2–catalysts by TiO2 addition resulted in a further increase in the nucleophility of the vanadyl oxygen and, as a consequence, an increase in the catalytic activity and selectivity for nicotinic acid formation.

  12. An improved solvent-free synthesis of flunixin and 2-(arylamino) nicotinic acid derivatives using boric acid as catalyst.

    Science.gov (United States)

    Yarhosseini, Mahsa; Javanshir, Shahrzad; Dolatkhah, Zahra; Dekamin, Mohammad G

    2017-12-01

    A simple solvent-free protocol for the preparation of flunixin, a potent non-narcotic, non-steroidal anti-inflammatory drugs is reported using boric acid as catalyst. Its salt, flunixin meglumine are then prepared under reflux in EtOH. This sustainable method are then extended for the synthesis of a series of 2-(arylamino) nicotinic acid derivatives. The present protocol combines non-hazardous neat conditions with associated benefits like excellent yield, straightforward workup, and use of readily available and safe catalyst in the absence of any solvent, which are important factors in the pharmaceutical industry. The pathway for catalytic activation of 2-chloronicotic acid with boric acid was also investigated using Gaussian 03 program package.

  13. Interaction Effect of 8-Week Aerobic Exercise and Omega-3 Fatty Acid

    Directory of Open Access Journals (Sweden)

    Gholamreza Khedri

    2013-03-01

    Full Text Available Background: Scientific evidence indicates the impact of aerobic exercise and omega-3 fatty acids - both –are for the improvement of the cardiovascular system .The purpose of this research was about studies interaction effect of 8 weeks aerobic exercise and omega- 3 fatty acids supplementation on plasma adiponectin concentration of elderly men.Materials and Methods: In this study, 36 male non-athletes aged were between 50 to 70 year age range of men aged the city of Genaveh. Statistical sample of 36 male non- athletes in the age range 50 to 70 years old randomly selected in four groups of nine persons, respectively, the first group: exercise supplemental omega-3, Group II: Exercise placebo group: supplementation with omega-3 groups quarter: placebo. Endurance exercise training program includes 24 sessions and 3 sessions per week, with duration and intensity was determined. (55-70% HRmax. Daily supplements of omega-3 fatty acids were 2 Capsule. Blood samples were taken after fasting 14 hours before the study and 48 hours after the last training session was conducted. The data Kolmogrov-Smirnov, t-test, One-Way Anova at significance level of p≤ 0.05 were analyzed in SPSS 17. Results: The results of research after 8 weeks showed that moderate-intensity aerobic exercise and omega-3 fatty acids supplementation, only increased in the exercise + omega-3 fatty acids group (7.8% that could not created a significant increase in plasma adiponectin concentration groups. Also in final of research did not show a significant difference between groups in compare after 8 weeks. Conclusion: The results showed that by aerobic exercise and use of omega-3 fatty acids and increase amounts of adiponectin and its anti boil property, perhaps maybe that, adiponectin by effect of its preservation has a great role in prevention and reduce of cardiovascular diseases.

  14. 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.

  15. 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

    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......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....../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...

  16. Aerobic Oxidation of Alcohols over Gold Catalysts: Role of Acid and Base

    DEFF Research Database (Denmark)

    Klitgaard, Søren Kegnæs; DeLa Riva, Andrew T.; Helveg, Stig

    2008-01-01

    Gold nanoparticles are deposited on potassium titanate nanowires and used as heterogeneous catalysts in the aerobic oxidation of benzyl alcohol in methanol to methyl benzoate at ambient conditions. The presence of a catalytic amount of base promotes the reaction and the formation of free benzoic...... acid during the reaction poisons the catalyst. The activity however, of the catalyst can be restored again by addition of base....

  17. SIMULTANEOUS ESTIMATION OF MECLIZINE HYDROCHLORIDE AND NICOTINIC ACID IN PHARMACEUTICAL DOSAGE FORM BY RP-HPLC METHOD

    OpenAIRE

    SUDHEER REDDY M, KRISHNA KARTHIK P, VINOD KUMAR K

    2013-01-01

    A simple, selective, rapid, precise and economical reverse phase high performance liquid chromatographicmethod has been developed for the simultaneous estimation of meclizine hydrochloride and nicotinic Acid frompharmaceutical formulation using C18 (25 cm x 4.6 mm i.d., 5

  18. 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

  19. 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

    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...

  20. 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

  1. 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.

  2. 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)

  3. Phosphatidic acid accumulation and catecholamine release in adrenal chromaffin cells: stimulation by high potassium and by nicotine, and effect of a diacylglycerol kinase inhibitor R 59 022.

    Science.gov (United States)

    Owen, P J; Jones, J A; Boarder, M R

    1991-09-01

    Using primary cultures of bovine adrenal chromaffin cells labelled with 32Pi, we show that stimulation with bradykinin, nicotine, or a depolarising concentration of potassium stimulates the accumulation of [32P]phosphatidic acid. The effects of nicotine and potassium are smaller than the effect of bradykinin, and are dependent entirely on extracellular calcium. The diacylglycerol kinase inhibitor R 59 022 attenuates the formation of phosphatidic acid by nicotine and depolarising concentrations of potassium. This inhibitor also blocks the nicotine and potassium stimulation of noradrenaline release from chromaffin cells. Using 45Ca2+ influx studies, we show that the nicotine-evoked calcium influx is also attenuated by R 59 022. These observations contrast with those in another report in which we showed that bradykinin stimulation of either [32P]phosphatidic acid accumulation or noradrenaline release is not affected by R 59 022. It is likely that the calcium influx produced by nicotine and depolarising potassium is blocked by R 59 022 by a mechanism that is independent of its ability to block diacylglycerol kinase. The nicotine- and potassium-stimulated [32P]phosphatidic acid accumulation is a consequence of this calcium influx and presumably reflects calcium activation of either phospholipase C or phospholipase D.

  4. 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)

  5. 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.

  6. 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

  7. Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose-limited chemostat culture.

    Science.gov (United States)

    Shah, Mihir V; van Mastrigt, Oscar; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    Currently, research is being focused on the industrial-scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial-scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose-limited chemostat cultures at a cultivation pH of 3.0 (pH medium. The experiments were carried out with the wild-type S. cerevisiae CEN.PK 113-7D and an engineered S. cerevisiae ADIS 244 expressing a heterologous dicarboxylic acid transporter (DCT-02) from Aspergillus niger, to examine whether it would be capable of exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two-thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial-scale production of fumaric acid are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

  8. 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

  9. Gamma-aminobutyric acid receptor genes and nicotine dependence: evidence for association from a case-control study.

    Science.gov (United States)

    Agrawal, Arpana; Pergadia, Michele L; Saccone, Scott F; Hinrichs, Anthony L; Lessov-Schlaggar, Christina N; Saccone, Nancy L; Neuman, Rosalind J; Breslau, Naomi; Johnson, Eric; Hatsukami, Dorothy; Montgomery, Grant W; Heath, Andrew C; Martin, Nicholas G; Goate, Alison M; Rice, John P; Bierut, Laura J; Madden, Pamela A F

    2008-06-01

    The gamma-aminobutyric acid receptor A (GABRA) gene clusters on chromosomes 4 and 5 have been examined previously for their association with alcohol and drug dependence phenotypes. Compelling evidence suggests that GABRA2 is associated with alcohol and drug dependence. However, no study has investigated whether genes in the GABA(A) gene clusters are associated with nicotine dependence, an important phenotype with a high correlation to persistent smoking, the single most preventable cause of mortality world-wide. Using data on 1050 nicotine-dependent cases and 879 non-dependent smoking controls, we used logistic regression to examine the association between single nucleotide polymorphisms (SNPs) in 13 genes in the GABA(A) receptor system as well as GABBR2 (a GABA(B) gene). We found evidence for association between four SNPs in GABRA4, two SNPs in GABRA2 and one SNP in GABRE with nicotine dependence. These included a synonymous polymorphism in GABRA2 (rs279858), lying in a highly conserved region, which has been shown previously to be associated with alcohol and drug dependence. A non-synonymous polymorphism (rs16859834/rs2229940) in GABRA4, also highly conserved, was associated at P-value of 0.03. Significant haplotypes associated with nicotine dependence were found for GABRA2. No evidence for epistatic interactions were noted. Our study did not find evidence for an association between GABBR2 gene and nicotine dependence. Given the potential role of compounds that enhance GABAergic neurotransmission in smoking cessation research, these findings have enormous potential for informing the wider field of addiction research.

  10. A novel nitrilase from Ralstonia eutropha H16 and its application to nicotinic acid production.

    Science.gov (United States)

    Fan, Haiyang; Chen, Lifeng; Sun, Huihui; Wang, Hualei; Ren, Yuhong; Wei, Dongzhi

    2017-08-01

    A novel aliphatic nitrilase, REH16, was found in Ralstonia eutropha H16 and overexpressed in Escherichia coli BL21(DE3), and its enzymatic properties were studied. The temperature and pH optima were 37 °C and 6.6, respectively, and the best thermostability of the nitrilase was observed at 25 °C, which preserved 95% of activity after 120 h of incubation. REH16 has a broad hydrolytic activity toward aliphatic and heterocyclic nitriles and showed high tolerance of 3-cyanopyridine; this enzyme could hydrolyze as high as 100 mM 3-cyanopyridine completely. To improve the 3-cyanopyridine conversion efficiency in an aqueous reaction system, water-miscible organic solvents were tested, and ethanol (10% v/v) was chosen as the optimal co-solvent. Finally, under optimized conditions, using the fed-batch reaction mode, total of 1050 mM 3-cyanopyridine was hydrolyzed completely in 20.8 h with eight substrate feedings, yielding 129.2 g/L production of nicotinic acid and thus showing a potential for industrial application.

  11. Bilayer tablets of atorvastatin calcium and nicotinic acid: formulation and evaluation.

    Science.gov (United States)

    Nirmal, Jayabalan; Saisivam, Srinivasan; Peddanna, Chintalapati; Muralidharan, Selvadurai; Godwinkumar, Sundaram; Nagarajan, Muthuraja

    2008-10-01

    The objective of the study is to formulate bilayer tablets consisting of atorvastatin calcium (AT) as an immediate release layer and nicotinic acid (NA) as an extended release layer. The immediate release layer was prepared using super disintegrant croscarmellose sodium and extended release layer using hydroxypropylmethyl cellulose (HPMC K100M). Both the matrix and bilayer tablets were evaluated for hardness, friability, weight variation, thickness, and drug content uniformity and subjected to in vitro drug release studies. The amount of AT and NA released at different time intervals were estimated by HPLC method. The bilayer tablets showed no significant change either in physical appearance, drug content or in dissolution pattern after storing at 40 degrees C/75% relative humiding (RH) for 3 months. The release of the drug from the tablet was influenced by the polymer content and it was much evident from thermogravimetry/differential thermal analysis (TG/DTA) analysis. The results indicated that the bilayer tablets could be a potential dosage form for delivering AT and NA.

  12. Activities of drug combinations against Mycobacterium tuberculosis grown in aerobic and hypoxic acidic conditions.

    Science.gov (United States)

    Piccaro, Giovanni; Giannoni, Federico; Filippini, Perla; Mustazzolu, Alessandro; Fattorini, Lanfranco

    2013-03-01

    Mycobacterium tuberculosis is exposed to hypoxia and acidity within granulomatous lesions. In this study, an acidic culture model of M. tuberculosis was used to test drug activity against aerobic 5-day-old (A5) and hypoxic 5-, 12-, and 19-day-old (H5, H12, and H19, respectively) bacilli after 7, 14, and 21 days of exposure. In A cultures, CFU and pH rapidly increased, while in H cultures growth stopped and pH increased slightly. Ten drugs were tested: rifampin (R), isoniazid (I), pyrazinamide (Z), ethambutol (E), moxifloxacin (MX), amikacin (AK), metronidazole (MZ), nitazoxanide (NZ), niclosamide (NC), and PA-824 (PA). Rifampin was the most active against A5, H5, H12, and H19 bacilli. Moxifloxacin and AK efficiently killed A5 and H5 cells, I was active mostly against A5 cells, Z was most active against H12 and H19 cells, and E showed low activity. Among nitrocompounds, NZ, NC, and PA were effective against A5, H5, H12, and H19 cells, while MZ was active against H12 and H19 cells. To kill all A and H cells, A5- and H5-active agents R, MX, and AK were used in combination with MZ, NZ, NC, or PA, in comparison with R-I-Z-E, currently used for human therapy. Mycobacterial viability was determined by CFU and a sensitive test in broth (day to positivity, MGIT 960 system). As shown by lack of regrowth in MGIT, the most potent combination was R-MX-AK-PA, which killed all A5, H5, H12, and H19 cells in 14 days. These observations demonstrate the sterilizing effect of drug combinations against cells of different M. tuberculosis stages grown in aerobic and hypoxic acidic conditions.

  13. Nicotine Gum

    Science.gov (United States)

    Nicotine chewing gum is used to help people stop smoking cigarettes. Nicotine chewing gum should be used together with a ... support groups, counseling, or specific behavioral change techniques. Nicotine gum is in a class of medications called ...

  14. 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 ...

  15. 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.

  16. Development and validation of RP-HPLC method for determination of Atorvastatin calcium and Nicotinic acid in combined tablet dosage form

    Directory of Open Access Journals (Sweden)

    Jaiprakash N. Sangshetti

    2016-09-01

    Full Text Available A simple, specific and accurate reverse phase liquid chromatographic method was developed for the simultaneous determination of Atorvastatin calcium and Nicotinic acid in tablet dosage forms. The analysis has been performed by using Agilent ZORBAX SB-C18 (150 × 4.6 mm, 3.5 u and mobile phase containing acetonitrile: distilled water (85:15 at pH 4.5 (adjusted with phosphoric acid. The detection was carried out at 261 nm with a flow rate of 1.0 ml/min. The retention times of Atorvastatin calcium and Nicotinic acid were 6.092 and 3.125 min, respectively. The method was validated according to ICH guidelines. The method was validated for specificity, precision, linearity, accuracy and robustness. The linearity for Atorvastatin calcium and Nicotinic acid were in the range of 2–12 and 10–80 μg/ml respectively. The recoveries of Atorvastatin calcium and Nicotinic acid were found to be in the range of 99.031% and 99.744% respectively. The proposed method was validated and successfully applied to the estimation of Atorvastatin calcium and Nicotinic acid in combined tablet formulation.

  17. Glutamic acid and folic acid production in aerobic and anaerobic probiotics

    Directory of Open Access Journals (Sweden)

    Zohre Taghi Abadi

    2018-03-01

    Full Text Available Introduction:From an industrial application or commercial point of view, glutamic acid is one of the most important amino acids and its microbial production has been reported from some bacteria. Regarding the role of probiotics to modulate human health and the ever-increasing demand of prebiotics in the food industry, in the current study, production of glutamic acid and folic acid from three probiotic bacteria (Bifidobacterium, Bifidobacterium bifidum, Sporolactobacillus was evaluated for the first time. Materials and methods: MRS broth and exclusive media was used for probiotic culture. The glutamic acid was identified using thin-layer chromatography and folic acid production was measured by folate kit. Each bacterium in terms of quality and quantity were measured by high pressure liquid chromatography. Results: Production of glutamic acid confirmed is based on the thin layer chromatography analysis and high pressure liquid chromatography results. In addition, it was observed that all three probiotics produce folic acid. The prevalence of folate in Bifidobacterium was measured as 315 mg/ml that was more than two other bacteria. Discussion and conclusion: To the best of our knowledge, this is the first report of microbial production of glutamic acid and folate from the probiotic bacteria. These beneficial bacteria can be used as a good source for mass production of these valuable compounds.

  18. Aerobic oxidation of aqueous ethanol using heterogeneous gold catalysts: Efficient routes to acetic acid and ethyl acetate

    DEFF Research Database (Denmark)

    Jørgensen, Betina; Christiansen, Sofie Egholm; Thomsen, M.L.D.

    2007-01-01

    The aerobic oxidation of aqueous ethanol to produce acetic acid and ethyl acetate was studied using heterogeneous gold catalysts. Comparing the performance of Au/MgAl2O4 and Au/TiO2 showed that these two catalysts exhibited similar performance in the reaction. By proper selection of the reaction......, the possibilities for producing ethyl acetate by the aerobic oxidation of ethanol is also studied. At low ethanol concentrations, the main product is acetic acid; at concentrations >60 wt%, it is ethyl acetate....... conditions, yields of 90-95% of acetic acid could be achieved at moderate temperatures and pressures. Based on our findings, a reaction pathway for the catalytic oxidation of ethanol via acetaldehyde to acetic acid is proposed, and the rate-determining step (RDS) in the mechanism is found to be the (possibly...

  19. Treatment of bromoamine acid wastewater using combined process of micro-electrolysis and biological aerobic filter.

    Science.gov (United States)

    Fan, Li; Ni, Jinren; Wu, Yanjun; Zhang, Yongyong

    2009-03-15

    The wastewater originated from the production of bromoamine acid was treated in a sequential system of micro-electrolysis (ME) and biological aerobic filter (BAF). Decolorization and COD(Cr) removal rate of the proposed system was investigated with full consideration of the influence of two major controlling factors such as organic loading rate (OLR) and hydraulic retention time (HRT). The removal rate of COD(Cr) was 81.2% and that of chrominance could be up to 96.6% at an OLR of 0.56 kg m(-3)d(-1) when the total HRT was 43.4h. Most of the chrominance was removed by the ME treatment, however, the BAF process was more effective for COD(Cr) removal. The GC-MS and HPLC-MS analysis of the contaminants revealed that 1-aminoanthraquinone, bromoamine acid and mono-sulfonated 1,2-dichlorobenzene were the main organic components in the wastewater. The reductive transformation of the anthraquinone derivatives in the ME reactor improved the biodegradability of the wastewater, and rendered the decolorization. After long-term of operation, it was observed that the predominant microorganisms immobilized on the BAF carriers were rod-shaped and globular. Four bacterial strains with apparent 16S rDNA fragments in the Denaturing Gradient Gel Electrophoresis (DGGE) profiles of BAF samples were identified as Variovorax sp., Sphingomonas sp., Mycobacterium sp., and Microbacterium sp.

  20. Treatment of bromoamine acid wastewater using combined process of micro-electrolysis and biological aerobic filter

    Energy Technology Data Exchange (ETDEWEB)

    Fan Li [Shenzhen Graduate School, Peking University, Key Laboratory for Environmental and Urban Sciences, Guang Dong 518055 (China); Department of Environmental Engineering, Peking University, Key Laboratory of Water and Sediment Sciences, Ministry of Education, Beijing 100871 (China); Ni Jinren [Shenzhen Graduate School, Peking University, Key Laboratory for Environmental and Urban Sciences, Guang Dong 518055 (China); Department of Environmental Engineering, Peking University, Key Laboratory of Water and Sediment Sciences, Ministry of Education, Beijing 100871 (China)], E-mail: nijinren@iee.pku.edu.cn; Wu Yanjun; Zhang Yongyong [Shenzhen Graduate School, Peking University, Key Laboratory for Environmental and Urban Sciences, Guang Dong 518055 (China); Department of Environmental Engineering, Peking University, Key Laboratory of Water and Sediment Sciences, Ministry of Education, Beijing 100871 (China)

    2009-03-15

    The wastewater originated from the production of bromoamine acid was treated in a sequential system of micro-electrolysis (ME) and biological aerobic filter (BAF). Decolorization and COD{sub Cr} removal rate of the proposed system was investigated with full consideration of the influence of two major controlling factors such as organic loading rate (OLR) and hydraulic retention time (HRT). The removal rate of COD{sub Cr} was 81.2% and that of chrominance could be up to 96.6% at an OLR of 0.56 kg m{sup -3} d{sup -1} when the total HRT was 43.4 h. Most of the chrominance was removed by the ME treatment, however, the BAF process was more effective for COD{sub Cr} removal. The GC-MS and HPLC-MS analysis of the contaminants revealed that 1-aminoanthraquinone, bromoamine acid and mono-sulfonated 1,2-dichlorobenzene were the main organic components in the wastewater. The reductive transformation of the anthraquinone derivatives in the ME reactor improved the biodegradability of the wastewater, and rendered the decolorization. After long-term of operation, it was observed that the predominant microorganisms immobilized on the BAF carriers were rod-shaped and globular. Four bacterial strains with apparent 16S rDNA fragments in the Denaturing Gradient Gel Electrophoresis (DGGE) profiles of BAF samples were identified as Variovorax sp., Sphingomonas sp., Mycobacterium sp., and Microbacterium sp.

  1. Treatment of bromoamine acid wastewater using combined process of micro-electrolysis and biological aerobic filter

    International Nuclear Information System (INIS)

    Fan Li; Ni Jinren; Wu Yanjun; Zhang Yongyong

    2009-01-01

    The wastewater originated from the production of bromoamine acid was treated in a sequential system of micro-electrolysis (ME) and biological aerobic filter (BAF). Decolorization and COD Cr removal rate of the proposed system was investigated with full consideration of the influence of two major controlling factors such as organic loading rate (OLR) and hydraulic retention time (HRT). The removal rate of COD Cr was 81.2% and that of chrominance could be up to 96.6% at an OLR of 0.56 kg m -3 d -1 when the total HRT was 43.4 h. Most of the chrominance was removed by the ME treatment, however, the BAF process was more effective for COD Cr removal. The GC-MS and HPLC-MS analysis of the contaminants revealed that 1-aminoanthraquinone, bromoamine acid and mono-sulfonated 1,2-dichlorobenzene were the main organic components in the wastewater. The reductive transformation of the anthraquinone derivatives in the ME reactor improved the biodegradability of the wastewater, and rendered the decolorization. After long-term of operation, it was observed that the predominant microorganisms immobilized on the BAF carriers were rod-shaped and globular. Four bacterial strains with apparent 16S rDNA fragments in the Denaturing Gradient Gel Electrophoresis (DGGE) profiles of BAF samples were identified as Variovorax sp., Sphingomonas sp., Mycobacterium sp., and Microbacterium sp

  2. Effect of chlorate, molybdate, and shikimic acid on Salmonella enterica serovar Typhimurium in aerobic and anaerobic cultures.

    Science.gov (United States)

    Oliver, Christy E; Beier, Ross C; Hume, Michael E; Horrocks, Shane M; Casey, Thomas A; Caton, Joel S; Nisbet, David J; Smith, David J; Krueger, Nathan A; Anderson, Robin C

    2010-04-01

    Experiments were conducted to determine factors that affect sensitivity of Salmonella enterica serovar Typhimurium to sodium chlorate (5mM). In our first experiment, cultures grown without chlorate grew more rapidly than those with chlorate. An extended lag before logarithmic growth was observed in anaerobic but not aerobic cultures containing chlorate. Chlorate inhibition of growth during aerobic culture began later than that observed in anaerobic cultures but persisted once inhibition was apparent. Conversely, anaerobic cultures appeared to adapt to chlorate after approximately 10h of incubation, exhibiting rapid compensatory growth. In anaerobic chlorate-containing cultures, 20% of total viable counts were resistant to chlorate by 6h and had propagated to 100% resistance (>10(9)CFU mL(-1)) by 24h. In the aerobic chlorate-containing cultures, 12.9% of colonies had detectable resistance to chlorate by 6h, but only 1% retained detectable resistance at 24h, likely because these cultures had opportunity to respire on oxygen and were thus not enriched via the selective pressure of chlorate. In another study, treatment with shikimic acid (0.34 mM), molybdate (1mM) or their combination had little effect on aerobic or anaerobic growth of Salmonella in the absence of added chlorate. As observed in our earlier study, chlorate resistance was not detected in any cultures without added chlorate. Chlorate resistant Salmonella were recovered at equivalent numbers regardless of treatment after 8h of aerobic or anaerobic culture with added chlorate; however, by 24h incubation chlorate sensitivity was completely restored to aerobic but not anaerobic cultures treated with shikimic acid or molybdate but not their combination. Results indicate that anaerobic adaptation of S. Typhimurium to sodium chlorate during pure culture is likely due to the selective propagation of low numbers of cells exhibiting spontaneous resistance to chlorate and this resistance is not reversible by

  3. [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 (p<0.01); the product Ca x P obtained important reductions at four and eight months; the total Cholesterol and Triglyceride was significant reduced at all periods, not being so for the LDL, although the HDL elevated to significant values at

  4. High-intensity interval training and β-hydroxy-β-methylbutyric free acid improves aerobic power and metabolic thresholds

    OpenAIRE

    Robinson, Edward H; Stout, Jeffrey R; Miramonti, Amelia A; Fukuda, David H; Wang, Ran; Townsend, Jeremy R; Mangine, Gerald T; Fragala, Maren S; Hoffman, Jay R

    2014-01-01

    Background Previous research combining Calcium β-hydroxy-β-methylbutyrate (CaHMB) and running high-intensity interval training (HIIT) have shown positive effects on aerobic performance measures. The purpose of this study was to examine the effect of β-hydroxy-β-methylbutyric free acid (HMBFA) and cycle ergometry HIIT on maximal oxygen consumption (VO2peak), ventilatory threshold (VT), respiratory compensation point (RCP) and time to exhaustion (Tmax) in college-aged men and women. Methods Thi...

  5. Cross-reactivity of acid-sensing ion channel and Na+–H+ exchanger antagonists with nicotinic acetylcholine receptors

    Science.gov (United States)

    Santos-Torres, Julio; Ślimak, Marta A; Auer, Sebastian; Ibañez-Tallon, Inés

    2011-01-01

    Abstract Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the mammalian central and peripheral nervous systems, where they contribute to neuronal excitability and synaptic communication. It has been reported that nAChRs are modulated by BK channels and that BK channels, in turn, are inhibited by acid-sensing ion channels (ASICs). Here we investigate the possible functional interaction between these channels in medial habenula (MHb) neurones. We report that selective antagonists of large-conductance calcium-activated potassium channels and ASIC1a channels, paxilline and psalmotoxin 1, respectively, did not induce detectable changes in nicotine-evoked currents. In contrast, the non-selective ASIC and Na+–H+ exchanger (NHE1) antagonists, amiloride and its analogues, suppressed nicotine-evoked responses in MHb neurones of wild-type and ASIC2 null mice, excluding a possible involvement of ASIC2 in the nAChR inhibition by amiloride. Zoniporide, a more selective inhibitor of NHE1, reversibly inhibited α3β4-, α7- and α4-containing (*) nAChRs in Xenopus oocytes and in brain slices, as well as in PS120 cells deficient in NHE1 and virally transduced with nAChRs, suggesting a generalized effect of zoniporide in most neuronal nAChR subtypes. Independently from nAChR antagonism, zoniporide profoundly blocked synaptic transmission onto MHb neurones without affecting glutamatergic and GABA receptors. Taken together, these results indicate that amiloride and zoniporide, which are clinically used to treat hypertension and cardiovascular disease, have an inhibitory effect on neuronal nAChRs when used experimentally at high doses. The possible cross-reactivity of these compounds with nAChRs in vivo will require further investigation. PMID:21911609

  6. Nicotine poisoning

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002510.htm Nicotine poisoning To use the sharing features on this page, please enable JavaScript. Nicotine is a bitter-tasting compound that naturally occurs ...

  7. Nicotine and tobacco

    Science.gov (United States)

    Withdrawal from nicotine; Smoking - nicotine addiction and withdrawal; Smokeless tobacco - nicotine addiction; Cigar smoking; Pipe smoking; Smokeless snuff; Tobacco use; Chewing tobacco; Nicotine addiction and tobacco

  8. Nicotinamide riboside and nicotinic acid riboside salvage in fungi and mammals. Quantitative basis for Urh1 and purine nucleoside phosphorylase function in NAD+ metabolism.

    Science.gov (United States)

    Belenky, Peter; Christensen, Kathryn C; Gazzaniga, Francesca; Pletnev, Alexandre A; Brenner, Charles

    2009-01-02

    NAD+ is a co-enzyme for hydride transfer enzymes and an essential substrate of ADP-ribose transfer enzymes and sirtuins, the type III protein lysine deacetylases related to yeast Sir2. Supplementation of yeast cells with nicotinamide riboside extends replicative lifespan and increases Sir2-dependent gene silencing by virtue of increasing net NAD+ synthesis. Nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiated by splitting the nucleoside into a nicotinamide base followed by nicotinamide salvage. Genetic evidence has established that uridine hydrolase, purine nucleoside phosphorylase, and methylthioadenosine phosphorylase are required for Nrk-independent utilization of nicotinamide riboside in yeast. Here we show that mammalian purine nucleoside phosphorylase but not methylthioadenosine phosphorylase is responsible for mammalian nicotinamide riboside kinase-independent nicotinamide riboside utilization. We demonstrate that so-called uridine hydrolase is 100-fold more active as a nicotinamide riboside hydrolase than as a uridine hydrolase and that uridine hydrolase and mammalian purine nucleoside phosphorylase cleave nicotinic acid riboside, whereas the yeast phosphorylase has little activity on nicotinic acid riboside. Finally, we show that yeast nicotinic acid riboside utilization largely depends on uridine hydrolase and nicotinamide riboside kinase and that nicotinic acid riboside bioavailability is increased by ester modification.

  9. Effect of flavonoids morin; quercetin and nicotinic acid on lipid metabolism of rats experimentally fed with triton

    Directory of Open Access Journals (Sweden)

    Kelly Fabiane Santos Ricardo

    2001-09-01

    Full Text Available Atherosclerosis is a coronary disease where deposition of lipids in the arteries leads to problems of blood circulation. The present work evaluates the action of the flavonoids morin, quercetin and nicotinic acid isolated in association on lipid metabolism in hyperlipidemic rats. Blood serum levels cholesterol, cholesterol-HDL, and triacylglycerids have been analysed following the intraperitoneal administration of the flavonoid compounds dissolved in propyleneglycol by in doses of 5mg/kg body weight. Quercetin presented the largest percentual reduction of cholesterol. The best results for cholesterol-HDL have been obtained with-nicotinic acid alone while morin-nicotinic acid combination showed the best triacylglycerols results. Results showed that flavonoids could be beneficious in the treatment of coronary diseases.Aterosclerose é uma doença coronária onde a deposição de lipídeos nas artérias leva a problemas na circulação sangüínea. O presente trabalho avalia a ação dos flavonóides morina, quercetina e ácido nicotínico isoladamente e em associação no metabolismo lipídico em ratos hiperlipidêmicos. Foram analisados os níveis de colesterol, colesterol- HDL e triacilgliceróis no soro sangüíneo após administração, via intraperitoneal, dos compostos flavonoídicos dissolvidos em propileno glicol na dose de 5mg/kg de peso corporal. Quercetina mostrou o maior percentual de redução do colesterol. Para colesterol-HDL, os melhores resultados foram obtidos com ácido nicotínico isoladamente, enquanto a associação morina-ácido nicotínico mostrou os melhores resultados para triacilgliceróis. Os resultados mostraram que os flavonóides podem ser benéficos no tratamento de doença coronoriana.

  10. The Aerobic Oxidation of Bromide to Dibromine Catalyzed by Homogeneous Oxidation Catalysts and Initiated by Nitrate in Acetic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Partenheimer, Walt; Fulton, John L.; Sorensen, Christina M.; Pham, Van Thai; Chen, Yongsheng

    2014-06-01

    A small amount of nitrate, ~0.002 molal, initiates the Co/Mn catalyzed aerobic oxidation of bromide compounds (HBr,NaBr,LiBr) to dibromine in acetic acid at room temperature. At temperatures 40oC or less , the reaction is autocatalytic. Co(II) and Mn(II) themselves and mixed with ionic bromide are known homogeneous oxidation catalysts. The reaction was discovered serendipitously when a Co/Br and Co/Mn/Br catalyst solution was prepared for the aerobic oxidation of methyaromatic compounds and the Co acetate contained a small amount of impurity i.e. nitrate. The reaction was characterized by IR, UV-VIS, MALDI and EXAFS spectroscopies and the coordination chemistry is described. The reaction is inhibited by water and its rate changed by pH. The change in these variables, as well as others, are identical to those observed during homogeneous, aerobic oxidation of akylaromatics. A mechanism is proposed. Accidental addition of a small amount of nitrate compound into a Co/Mn/Br/acetic acid mixture in a large, commercial feedtank is potentially dangerous.

  11. Nicotinic Acid Receptor GPR109A Is Down-Regulated in Human Macrophage-Derived Foam Cells

    Science.gov (United States)

    Chai, Joshua T.; Digby, Janet E.; Ruparelia, Neil; Jefferson, Andrew; Handa, Ashok; Choudhury, Robin P.

    2013-01-01

    Nicotinic acid (NA) regresses atherosclerosis in human imaging studies and reduces atherosclerosis in mice, mediated by myeloid cells, independent of lipoproteins. Since GPR109A is expressed by human monocytes, we hypothesized that NA may drive cholesterol efflux from foam cells. In THP-1 cells NA suppressed LPS-induced mRNA transcription of MCP-1 by 76.6±12.2% (Pfoam cells by 37.7±3.1% (Pfoam cells on either cholesterol efflux or key RCT genes transcription. Upon foam cell induction, NA lost its effect on PPARγ and cAMP pathways, since its receptor, GPR109A, was down-regulated by foam cell transformation. This observation was confirmed in explanted human carotid plaques. In conclusion, despite NA’s anti-inflammatory effect on human macrophages, it has no effect on foam cells in reverse cholesterol transport; due to GPR109A down-regulation. PMID:23658787

  12. An improved nitrilase-mediated bioprocess for synthesis of nicotinic acid from 3-cyanopyridine with hyperinduced Nocardia globerula NHB-2.

    Science.gov (United States)

    Sharma, Nitya Nand; Sharma, Monica; Bhalla, Tek Chand

    2011-09-01

    Nitrilase of Nocardia globerula NHB-2 was induced by short-chain aliphatic nitriles (valeronitrile > isobutyronitrile > butyronitrile > propionitrile) and exhibited activity towards aromatic nitriles (benzonitrile > 3-cyanopyridine > 4-cyanopyridine > m-tolunitrile > p-tolunitrile). Hyperinduction of nitrilase (6.67 U mg (DCW) (-1), 18.7 U mL(-1)) was achieved in short incubation time (30 h, 30°C) through multiple feeding of isobutyronitrile in the growth medium. The nitrilase of this organism exhibits both substrate and product inhibition effects. In a fed batch reaction at 1 L scale using hyperinduced resting cells corresponding to 10 U mL(-1) nitrilase activity (1.5 mg(DCW) mL(-1)), a total of 123.11 g nicotinic acid was produced at a rate of 24 g h(-1) g (DCW) (-1).

  13. Effect of Applying Molasses and Propionic Acid on Fermentation Quality and Aerobic Stability of Total Mixed Ration Silage Prepared with Whole-plant Corn in Tibet

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2014-03-01

    Full Text Available The objective of this study was to evaluate the effects of molasses and propionic acid on the fermentation quality and aerobic stability of total mixed ration (TMR silages prepared with whole-plant corn in Tibet. TMR (354 g/kg DM was ensiled with four different treatments: no additive (control, molasses (M, propionic acid (P, and molasses+propionic acid (PM, in laboratory silos (250 mL and fermented for 45 d. Silos were opened and silages were subjected to an aerobic stability test for 12 days, in which chemical and microbiological parameters of TMR silages were measured to determined the aerobic deterioration. After 45 d of ensiling, the four TMR silages were of good quality with low pH value and ammonia/total N (AN, and high lactic acid (LA content and V-scores. M silage showed the highest (p105 cfu/g FM, however, it appeared to be more stable as indicated by a delayed pH value increase. P and PM silages showed fewer yeasts (<105 cfu/g FM (p<0.05 and were more stable than the control and M silages during aerobic exposure. It was concluded that M application increased LA content and improved aerobic stability of TMR silage prepared with whole-plant corn in Tibet. P application inhibited lactic acid production during ensiling, and apparently preserved available sugars which stimulated large increases in lactic acid during aerobic exposure stage, which resulted in greater aerobic stability of TMR silage.

  14. Effect of Applying Molasses and Propionic Acid on Fermentation Quality and Aerobic Stability of Total Mixed Ration Silage Prepared with Whole-plant Corn in Tibet

    Science.gov (United States)

    Chen, Lei; Guo, Gang; Yuan, Xianjun; Shimojo, Masataka; Yu, Chengqun; Shao, Tao

    2014-01-01

    The objective of this study was to evaluate the effects of molasses and propionic acid on the fermentation quality and aerobic stability of total mixed ration (TMR) silages prepared with whole-plant corn in Tibet. TMR (354 g/kg DM) was ensiled with four different treatments: no additive (control), molasses (M), propionic acid (P), and molasses+propionic acid (PM), in laboratory silos (250 mL) and fermented for 45 d. Silos were opened and silages were subjected to an aerobic stability test for 12 days, in which chemical and microbiological parameters of TMR silages were measured to determined the aerobic deterioration. After 45 d of ensiling, the four TMR silages were of good quality with low pH value and ammonia/total N (AN), and high lactic acid (LA) content and V-scores. M silage showed the highest (p105 cfu/g FM), however, it appeared to be more stable as indicated by a delayed pH value increase. P and PM silages showed fewer yeasts (ensiling, and apparently preserved available sugars which stimulated large increases in lactic acid during aerobic exposure stage, which resulted in greater aerobic stability of TMR silage. PMID:25049961

  15. Determination of trigonelline, nicotinic acid, and caffeine in Yunnan Arabica coffee by microwave-assisted extraction and HPLC with two columns in series.

    Science.gov (United States)

    Liu, Hongcheng; Shao, Jinliang; Li, Qiwan; Li, Yangang; Yan, Hong Mei; He, Lizhong

    2012-01-01

    A simple, rapid method was developed for simultaneous extraction of trigonelline, nicotinic acid, and caffeine from coffee, and separation by two chromatographic columns in series. The trigonelline, nicotinic acid, and caffeine were extracted with microwave-assisted extraction (MAE). The optimal conditions selected were 3 min, 200 psi, and 120 degrees C. The chromatographic separation was performed with two columns in series, polyaromatic hydrocarbon C18 (250 x 4.6 mm id, 5 microm particle size) and Bondapak NH2 (300 x 3.9 mm id, 5 microm particle size). Isocratic elution was with 0.02 M phosphoric acid-methanol (70 + 30, v/v) mobile phase at a flow rate of 0.8 mL/min. Good recoveries and RSD values were found for all analytes in the matrix. The LOD of the three compounds was 0.02 mg/L, and the LOQ was 0.005% in the matrix. The concentrations of trigonelline, nicotinic acid, and caffeine in instant coffee, roasted coffee, and raw coffee (Yunnan Arabica coffee) were assessed by MAE and hot water extraction; the correlation coefficients between concentrations of the three compounds obtained were close to 1.

  16. Direct Production of (R)-3-Hydroxybutyric Acid of High Optical Purity by Halomonas sp. OITC1261 Under Aerobic conditions.

    Science.gov (United States)

    Yokaryo, Hiroto; Teruya, Morimi; Hanashiro, Ryuji; Goda, Masahiro; Tokiwa, Yutaka

    2018-02-01

    The chiral compound (R)-3-hydroxybutyric acid (R-3HB) has some important physiological functions in the human body and can also be applied as a functional material for industrial products. A novel Halomonas sp. OITC1261 isolated from a coastal sediment is selected for efficient production of R-3HB. This strain secreted R-3HB of high optical purity into the extracellular medium while maintaining poly(3-hydroxybutyric acid) (PHB) inside the microbial cell under aerobic conditions. There is a possibility that R-3HB is generated independently of PHB. Under aerobic cultivation, 58 g L -1 (0.65 g L -1  h -1 ) of R-3HB was produced simultaneously with 27 g L -1 (0.30 g L -1  h -1 ) of PHB. This direct production method of R-3HB contributes to the improvement of mass production technology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Effects of four short-chain fatty acids or salts on fermentation characteristics and aerobic stability of alfalfa (Medicago sativa L.) silage.

    Science.gov (United States)

    Yuan, Xian J; Wen, Ai Y; Wang, Jian; Desta, Seare T; Dong, Zhi H; Shao, Tao

    2018-01-01

    The objective of the present study was to evaluate the effects of four chemicals on the fermentation quality and aerobic stability of alfalfa (Medicago sativa L.) silage. Wilted alfalfa was ensiled without additive (control), or with formic acid (FA), potassium diformate (KDF), sodium diacetate (SDA) or calcium propionate (CAP). After 60 days of ensiling, the pH values in FA, KDF and SDA silages were lower (P < 0.05) compared to that of control and CAP silages, and chemicals (P < 0.05) decreased butyric acid and ammonia N concentrations and populations of aerobic bacteria and yeasts compared to the control. The SDA and CAP silages had a higher (P < 0.05) lactic acid bacteria content compared to the FA and KDF silages. The SDA and CAP silages had higher (P < 0.05) acetic and propionic acid contents compared to the other silages, respectively. The ammonia N concentrations in the FA and KDF silages were lower compared to the other silages during the first 5 days of aerobic exposure, and then increased sharply to 105 and 100 g kg -1 total N, respectively, which was higher (P < 0.05) than that of the SDA and CAP silages on day 9 of aerobic exposure. Yeasts and aerobic bacteria counts in SDA silage slowly increased and remained at lower levels compared to the other silages after 7 days of aerobic exposure. Additives prolonged the aerobic stability duration compared to the control, and the SDA and CAP silages remained stable for more than 216 h, followed by the KDF and FA silages (202 and 196 h, respectively). © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  18. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics.

    Science.gov (United States)

    Benowitz, Neal L

    2009-01-01

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

  19. 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 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...

  20. 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.

  1. 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

  2. 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

  3. Nicotinic acid effects on insulin sensitivity and hepatic lipid metabolism: an in vivo to in vitro study.

    Science.gov (United States)

    Blond, E; Rieusset, J; Alligier, M; Lambert-Porcheron, S; Bendridi, N; Gabert, L; Chetiveaux, M; Debard, C; Chauvin, M-A; Normand, S; Roth, H; de Gouville, A-C; Krempf, M; Vidal, H; Goudable, J; Laville, M

    2014-06-01

    Our aim was to characterize the effects and the underlying mechanisms of the lipid-regulating agent Niaspan(®) on both insulin action and triglyceride decrease in 20 nondiabetic, dyslipidemic men with metabolic syndrome receiving Niaspan(®) (2 g/day) or placebo for 8 weeks in a randomized, cross-over study. The effects on plasma lipid profile were characterized at the beginning and the end of each treatment period; insulin sensitivity was assessed using the 2-step euglycemic hyperinsulinemic clamp and VLDL-triglyceride turnover by measuring plasma glycerol enrichment, both at the end of each treatment period. The mechanism of action of nicotinic acid was studied in HuH7 and mouse primary hepatocytes. Lipid profile was improved after Niaspan(®) treatment with a significant-28% decrease in triglyceride levels, a+17% increase in HDL-C concentration and unchanged levels of fasting nonesterified fatty acid. VLDL-tri-glyceride production rate was markedly reduced after Niaspan(®) (-68%). However, the treatment induced hepatic insulin resistance, as assessed by reduced inhibition of endogenous glucose production by insulin (0.7±0.4 vs. 1.0±0.5 mg/kg · min, pinsulin sensitivity index (4.8±1.8 vs. 3.2±1.6, pinsulin action in HuH7 and primary hepatocytes, independently of the activation of hepatic PKCε. This effect was associated with an increase in diacylglycerol and a decrease in tri-glyceride contents that occurred in the absence of modification of DGAT2 expression and activity. Eight weeks of Niaspan(®) treatment in dyslipidemic patients with metabolic syndrome induce hepatic insulin resistance. The mechanism could involve an accumulation of diacylglycerol and an alteration of insulin signaling in hepatocytes. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Synthesis and investigation of enneachloroditungstates (3) with hydroxyquinoline, mercaptoquinoline, nicotinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Spitsyn, V.I.; Felin, M.G.; Zhadanov, B.V.; Subbotina, N.A.; Mozgin, S.V. (Moskovskij Gosudarstvennyj Univ. (USSR))

    1984-08-01

    Complexes of (HL)/sub 3/W/sub 2/Cl/sub 9/ (L-8-hydroxyquinoline, 8-mercaptoquinoline, 4-pyridine carboxylic acid) were prepared by exchange reaction of (NH/sub 4/)/sub 3/W/sub 2/Cl/sub 9/ with corresponding ligands in hydrochloric acid. Their structure and composition were supported by the data of element analysis, infrared and electron spectroscopy, thermomagnetic and thermogravimetric measurements. Dehydrohalogenation of complexes was conducted and intermediate products characterized by the series of physicochemical methods were separated.

  5. Specific circulating phospholipids, acylcarnitines, amino acids and biogenic amines are aerobic exercise markers.

    Science.gov (United States)

    Felder, Thomas K; Ring-Dimitriou, Susanne; Auer, Simon; Soyal, Selma M; Kedenko, Ludmilla; Rinnerthaler, Mark; Cadamuro, Janne; Haschke-Becher, Elisabeth; Aigner, Elmar; Paulweber, Bernhard; Patsch, Wolfgang

    2017-07-01

    Regular aerobic exercise provides beneficial effects on human health and reduces all-cause mortality. Aerobic exercise has profound metabolic effects, and specific metabolites may reflect physiological changes. We aimed to identify endogenous metabolites that distinguish the trained from the untrained state to increase the spectrum of analytes amenable for hypothesis testing and to expand understanding of putative beneficial pathways. Cross sectional laboratory repeated measures study. Exercise testing was performed in 37 healthy male participants and serum samples were obtained before and after completion of a ten-week standardized exercise program. Samples were analyzed for routine clinical parameters and for 188 endogenous metabolites by LC-MS/MS. Indicating the effectiveness of the intervention program, parameters of sport physiology were different after training. After correcting for multiple testing, serum concentrations of several metabolites differed between the trained and untrained state. Serine and glutamate decreased in response to exercise, whereas sarcosine and kynurenine increased. Phosphatidylcholines showed a mixed response in that four species increased and three decreased. However, all seven lysophosphatidylcholines and all four plasmalogens that differed between the trained and untrained state, increased. One short-chain acylcarnitine also decreased. In receiver operator characteristics analyses, sarcosine displayed the highest AUC value (0.839; 95% CI: 0.734-0.926) in discriminating the pre- from the post-trained state. Our study detected metabolites that clearly differentiate the trained from the untrained state. These metabolites may be targeted in mechanistic studies to understand underlying biochemical pathways and could serve to improve the design, monitoring and individualization of training programs. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  6. Decolorization of anthraquinone dye intermediate and its accelerating effect on reduction of azo acid dyes by Sphingomonas xenophaga in anaerobic-aerobic process.

    Science.gov (United States)

    Lu, Hong; Zhou, Jiti; Wang, Jing; Ai, Haixin; Zheng, Chunli; Yang, Yusuo

    2008-09-01

    Decolorization of 1-aminoanthraquinone-2-sulfonic acid (ASA-2) and its accelerating effect on the reduction of azo acid dyes by Sphingomonas xenophaga QYY were investigated. The study showed that ASA-2 could be efficiently decolorized by strain QYY under aerobic conditions according to the analysis of total organic carbon removal and UV-VIS spectra changes. Moreover, strain QYY was able to reduce azo acid dyes under anaerobic conditions. The effects of various operating conditions such as carbon sources, temperature, and pH on the reduction rate were studied. It was demonstrated that ASA-2 used as a redox mediator could accelerate the reduction process. Consequently the reduction of azo acid dyes mediated by ASA-2 and the decolorization of ASA-2 with strain QYY could be achieved in an anaerobic-aerobic process.

  7. Aerobic biodegradation of 2,2'-dithiodibenzoic acid produced from dibenzothiophene metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Young, R.F.; Cheng, S.M.; Fedorak, P.M. [University of Alberta, Edmonton, AB (Canada). Dept. of Biological Science

    2006-01-15

    Dibenzothiophene is a sulfur heterocycle found in crude oils and coal. The biodegradation of dibenzothiophene through the Kodama pathway by Pseudomonas sp. strain BT1d leads to the formation of three disulfides: 2-oxo-2-(2-thiophenyl)ethanoic acid disulfide, 2-oxo-2-(2-thiophenyl)ethanoic acid-2-benzoic acid disulfide, and 2,2'-dithiodibenzoic acid. When provided as the carbon and sulfur source in liquid medium, 2,2'-dithiodibenzoic acid was degraded by soil enrichment cultures. Two bacterial isolates, designated strains RM1 and RM6, degraded 2,2'-dithiodibenzoic acid when combined in the medium. Isolate RM6 was found to have an absolute requirement for vitamin B{sub 12}, and it degraded 2,2'-dithiodibenzoic acid in pure culture when the medium was supplemented with this vitamin. Isolate RM6 also degraded 2,2'-dithiodibenzoic acid in medium containing sterilized supernatants from cultures of isolate RM1 grown on glucose or benzoate. Isolate RM6 was identified as a member of the genus Variovorax using the Biolog system and 16S rRNA gene analysis. Although the mechanism of disulfide metabolism could not be determined, benzoic acid was detected as a transient metabolite of 2,2'-dithiodibenzoic acid biodegradation by Variovorax sp. strain RM6. In pure culture, this isolate mineralized 2,2'-dithiodibenzoic acid, releasing 59% of the carbon as carbon dioxide and 88% of the sulfur as sulfate.

  8. Aerobic Biodegradation of 2,2′-Dithiodibenzoic Acid Produced from Dibenzothiophene Metabolites

    Science.gov (United States)

    Young, Rozlyn F.; Cheng, Stephanie M.; Fedorak, Phillip M.

    2006-01-01

    Dibenzothiophene is a sulfur heterocycle found in crude oils and coal. The biodegradation of dibenzothiophene through the Kodama pathway by Pseudomonas sp. strain BT1d leads to the formation of three disulfides: 2-oxo-2-(2-thiophenyl)ethanoic acid disulfide, 2-oxo-2-(2-thiophenyl)ethanoic acid-2-benzoic acid disulfide, and 2,2′-dithiodibenzoic acid. When provided as the carbon and sulfur source in liquid medium, 2,2′-dithiodibenzoic acid was degraded by soil enrichment cultures. Two bacterial isolates, designated strains RM1 and RM6, degraded 2,2′-dithiodibenzoic acid when combined in the medium. Isolate RM6 was found to have an absolute requirement for vitamin B12, and it degraded 2,2′-dithiodibenzoic acid in pure culture when the medium was supplemented with this vitamin. Isolate RM6 also degraded 2,2′-dithiodibenzoic acid in medium containing sterilized supernatants from cultures of isolate RM1 grown on glucose or benzoate. Isolate RM6 was identified as a member of the genus Variovorax using the Biolog system and 16S rRNA gene analysis. Although the mechanism of disulfide metabolism could not be determined, benzoic acid was detected as a transient metabolite of 2,2′-dithiodibenzoic acid biodegradation by Variovorax sp. strain RM6. In pure culture, this isolate mineralized 2,2′-dithiodibenzoic acid, releasing 59% of the carbon as carbon dioxide and 88% of the sulfur as sulfate. PMID:16391083

  9. Farmacologia da niacina ou ácido nicotínico Pharmacology of niacin or nicotinic acid

    Directory of Open Access Journals (Sweden)

    Raul D. Santos

    2005-10-01

    Full Text Available Niacina ou ácido nicotínico é uma vitamina solúvel com propriedades hipolipemiantes. Niacina reduz triglicérides (20% - 50%, LDL (5% - 25%, e aumenta HDL (15% - 35%. O estudo Coronary Drug Project mostrou que o uso de niacina foi associado com redução de eventos coronários e mortalidade total, e mais recentemente, foi demonstrado que niacina combinada com outras drogas hipolipemiantes pode atenuar a progressão da aterosclerose coronária. A niacina parece reduzir a mobilização de ácidos graxos livres dos adipócitos, agindo em receptores específicos, diminuindo a formação de lipoproteínas ricas em triglicérides pelo fígado. Existem duas formas de niacina, uma de absorção rápida (cristalina, mais comumente associada com flushing, e outra de liberação extendida, recentemente referida como de melhor tolerabilidade. O uso de niacina pode associar-se com dispepsia, aumento dos níveis plasmáticos de enzimas hepáticas e também com modestas elevações na glicose e ácido úrico, ao menos na utilização de doses até 2g / dia da forma de liberação prolongada.Niacin or nicotinic acid is a soluble vitamin with hypolipidemic properties. Niacin reduces triglycerides (20 50%, LDL-c (5-25%, and raises HDL c (15-35%. The Coronary Drug Project study showed that the use of niacin was associated with reduction on coronary events and total mortality, and more recently it has been demonstrated that niacin combined with other hypolipidemic drugs can attenuate the progression of coronary atherosclerosis. Niacin appears to reduce the mobilization of free fatty acids from the adipocytes, acting on specific receptors, diminishing the liver formation of triglyceride-rich lipoproteins. There are two forms of niacin, one of rapid absorption (crystalline, more commonly associated with flushing, and another of extended release, recently reported to be better tolerated. The use of niacin can be associated with dyspepsia, increased plasma levels

  10. Mixed Effects Modeling Using Stochastic Differential Equations: Illustrated by Pharmacokinetic Data of Nicotinic Acid in Obese Zucker Rats.

    Science.gov (United States)

    Leander, Jacob; Almquist, Joachim; Ahlström, Christine; Gabrielsson, Johan; Jirstrand, Mats

    2015-05-01

    Inclusion of stochastic differential equations in mixed effects models provides means to quantify and distinguish three sources of variability in data. In addition to the two commonly encountered sources, measurement error and interindividual variability, we also consider uncertainty in the dynamical model itself. To this end, we extend the ordinary differential equation setting used in nonlinear mixed effects models to include stochastic differential equations. The approximate population likelihood is derived using the first-order conditional estimation with interaction method and extended Kalman filtering. To illustrate the application of the stochastic differential mixed effects model, two pharmacokinetic models are considered. First, we use a stochastic one-compartmental model with first-order input and nonlinear elimination to generate synthetic data in a simulated study. We show that by using the proposed method, the three sources of variability can be successfully separated. If the stochastic part is neglected, the parameter estimates become biased, and the measurement error variance is significantly overestimated. Second, we consider an extension to a stochastic pharmacokinetic model in a preclinical study of nicotinic acid kinetics in obese Zucker rats. The parameter estimates are compared between a deterministic and a stochastic NiAc disposition model, respectively. Discrepancies between model predictions and observations, previously described as measurement noise only, are now separated into a comparatively lower level of measurement noise and a significant uncertainty in model dynamics. These examples demonstrate that stochastic differential mixed effects models are useful tools for identifying incomplete or inaccurate model dynamics and for reducing potential bias in parameter estimates due to such model deficiencies.

  11. Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity.

    Science.gov (United States)

    Abdel-Aziz, Hatem A; Aboul-Fadl, Tarek; Al-Obaid, Abdul-Rahman M; Ghazzali, Mohamed; Al-Dhfyan, Abdullah; Contini, Alessandro

    2012-09-01

    Novel 6-aryl-2-methylnicotinic acid hydrazides 4a-c and their corresponding hydrazones 5a-c and 6a-i were synthesized. X-ray single crystal diffraction of 6h confirmed the chemical structure of hydrazones 6a-i. Antiproliferative activity of the synthetic compounds was investigated against K562 leukemia cell lines. Variable cell growth inhibitory activities were obtained with IC₅₀ range from 24.99 to 66.78 μM where the compound 6c exhibited the maximum activity. Structure activity relationship analysis has been performed and a common pharmacophore model for the synthesized derivatives has been obtained by using the pharmacophore elucidation module of the software MOE. The best model obtained is characterized by two projected locations of potential H-bond donors (F 3 and F4) and two Aromatic annotations (F1 and F2).

  12. Hydrolysis of 4-Hydroxybenzoic Acid Esters (Parabens) and Their Aerobic Transformation into Phenol by the Resistant Enterobacter cloacae Strain EM

    Science.gov (United States)

    Valkova, Nelly; Lépine, François; Valeanu, Loredana; Dupont, Maryse; Labrie, Louisette; Bisaillon, Jean-Guy; Beaudet, Réjean; Shareck, François; Villemur, Richard

    2001-01-01

    Enterobacter cloacae strain EM was isolated from a commercial dietary mineral supplement stabilized by a mixture of methylparaben and propylparaben. It harbored a high-molecular-weight plasmid and was resistant to high concentrations of parabens. Strain EM was able to grow in liquid media containing similar amounts of parabens as found in the mineral supplement (1,700 and 180 mg of methyl and propylparaben, respectively, per liter or 11.2 and 1.0 mM) and in very high concentrations of methylparaben (3,000 mg liter−1, or 19.7 mM). This strain was able to hydrolyze approximately 500 mg of methyl-, ethyl-, or propylparaben liter−1 (3 mM) in less than 2 h in liquid culture, and the supernatant of a sonicated culture, after a 30-fold dilution, was able to hydrolyze 1,000 mg of methylparaben liter−1 (6.6 mM) in 15 min. The first step of paraben degradation was the hydrolysis of the ester bond to produce 4-hydroxybenzoic acid, followed by a decarboxylation step to produce phenol under aerobic conditions. The transformation of 4-hydroxybenzoic acid into phenol was stoichiometric. The conversion of approximately 500 mg of parabens liter−1 (3 mM) to phenol in liquid culture was completed within 5 h without significant hindrance to the growth of strain EM, while higher concentrations of parabens partially inhibited its growth. PMID:11375144

  13. Fermentation acids, aerobic fungal growth, and intake of napiergrass ensiled with nonfiber carbohydrates.

    Science.gov (United States)

    Yang, C M J; Huang, S C; Chang, T; Cheng, Y H; Chang, C T

    2004-03-01

    This study evaluated fermentation characteristics and fungal numbers of napiergrass silages prepared with and without added raw or heated corn meal (10%, fresh-weight basis) at ensiling. Corn was added to napiergrass so that the silage would contain concentrate similar to that of corn silage with minimum grain content. The silages treated with raw or heated corn were fed to dairy does to compare voluntary silage consumption. After 8 wk of fermentation, pH for silage treated with heated corn was lowest, and that for napiergrass ensiled alone was highest among the treatments. The addition of corn increased lactic acid, but propionic and butyric acids were also elevated. Acetic acid decreased in response to the supplementation of corn but remained the dominant acid for all silages. Numbers of fungi (yeasts plus molds) in silages did not differ significantly at silo opening or after 24 h of exposure to air. However, the numbers of fungi at 48 h in aerated silages containing corn were lower than were the fungi counts in the control silage. When the silages were offered free choice along with concentrate at a fixed rate, dairy does tended to consume more silage treated with heated corn than raw corn. Whole-tract nutrient digestibility and serum glucose and urea N were not altered. These results indicate that the addition of either raw or heated corn meal to napiergrass at ensiling was beneficial to silage fermentation quality because it decreased pH, increased lactic acid, and apparently suppressed fungal populations via elevated antifungal acids. A further advantage of heated corn vs. raw corn was increased silage intake.

  14. Molecular regulation of fatty acid oxidation in skeletal muscle during aerobic exercise

    DEFF Research Database (Denmark)

    Lundsgaard, Annemarie; Fritzen, Andreas Mæchel; Kiens, Bente

    2018-01-01

    This review summarizes how fatty acid (FA) oxidation is regulated in skeletal muscle during exercise. From the available evidence it seems that acetyl-CoA availability in the mitochondrial matrix adjusts FA oxidation to exercise intensity and duration. This is executed at the step of mitochondria...... in the tricarboxylic acid (TCA) cycle. FA oxidation during exercise is also determined by FA availability to mitochondria, dependent on trans-sarcolemmal FA uptake via cluster of differentiation 36/SR-B2 (CD36) and FAs mobilized from myocellular lipid droplets....

  15. Copper/ascorbic acid dyad as a catalytic system for selective aerobic oxidation of amines

    Czech Academy of Sciences Publication Activity Database

    Šrogl, Jiří; Voltrová, Svatava

    2009-01-01

    Roč. 11, č. 4 (2009), s. 843-845 ISSN 1523-7060 Institutional research plan: CEZ:AV0Z40550506 Keywords : copper * ascorbic acid * oxidative deamination Subject RIV: CC - Organic Chemistry Impact factor: 5.420, year: 2009

  16. Prefrontal gamma-aminobutyric Acid type a receptor insertion controls cue-induced relapse to nicotine seeking

    NARCIS (Netherlands)

    Lubbers, B.R.; van Mourik, Y.; Schetters, D.; Smit, A.B.; de Vries, T.J.; Spijker, S.

    2014-01-01

    Background: 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

  17. Gas-phase studies of copper catalyzed aerobic cross coupling of thiol esters and arylboronic acids

    Czech Academy of Sciences Publication Activity Database

    Tsybizová, A.; Schröder, Detlef; Roithová, J.; Henke, A.; Šrogl, Jiří

    2014-01-01

    Roč. 27, č. 3 (2014), s. 198-203 ISSN 0894-3230 R&D Projects: GA ČR GAP207/12/0846 Grant - others:GA ČR(CZ) GAP207/11/0338 Institutional support: RVO:61388963 Keywords : boronic acids * catalysis * copper * cross coupling * electrospray ionization * mass spectrometry * kinetic studies Subject RIV: CC - Organic Chemistry Impact factor: 1.380, year: 2014

  18. Conjugated linoleic acid supplementation does not maximize motor performance and abdominal and trunk fat loss induced by aerobic training in overweight women

    Directory of Open Access Journals (Sweden)

    Fábio Luiz Cheche PINA

    Full Text Available ABSTRACT Objective: To analyze the effect of eight weeks of conjugated linoleic acid supplementation on physical performance, and trunk and abdominal fat in overweight women submitted to an aerobic training program. Methods: Twenty-eight overweight women (body mass index ³25 kg/m2 were divided randomly and double-blindly to receive conjugated linoleic acid or placebo, both associated with an aerobic exercise program (frequency = three times a week, duration=30 min/session, intensity=80% of maximum heart rate. Conjugated linoleic acid (3.2 g and placebo (4.0 g supplements were consumed daily (four capsules for eight weeks. Maximum speed and time to exhaustion were determined in incremental treadmill test. Trunk fat was estimated by dual-energy X-Ray absorptiometry. Waist circumference was used as indicator of abdominal fat. Results: Main effect of time (p0.05. Similarly, significant reductions (p0.05. Conclusion: The results of this study suggest that conjugated linoleic acid supplementation does not maximize motor performance, and loss of body and abdominal fat induced by aerobic training in overweight women.

  19. Nicotine Addiction

    NARCIS (Netherlands)

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

    2003-01-01

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

  20. Effects of Dietary Fatty Acids on Juvenile Salmon Growth, Biochemistry, and Aerobic Performance: A Laboratory Rearing Experiment

    Science.gov (United States)

    Litz, M. N. C.; Miller, J. A.; Copeman, L.; Hurst, T. P.

    2016-02-01

    Juvenile salmon undergo important physiological and ecological transitions as they migrate from freshwater to the ocean, a phase characterized by rapid growth and high mortality. It is becoming increasing clear that variations in nutritional quality of marine prey may be as important as prey quantity in determining salmon survival during this critical period in their life history. Growth potential, and hence survival, may be related to the size when salmon first become piscivorous. We tested the hypothesis that prey nutrient composition and predator nutritional history affects growth, biochemistry, and performance in a population of subyearling Chinook salmon (Onchorynchus tshawytscha). Salmon were reared for 12 weeks on three energetically similar experimental diets. Diets were created with ratios of docosahexaenoic acid (DHA) to eicosapentaenoic acid (EPA) of 0.56, 0.94, and 1.47 by altering the amount of krill, anchovy, and two fatty acid supplements. Tagged salmon reared on the high DHA:EPA anchovy diet trended towards faster growth (0.33±0.05 mm d-1) compared to fish reared on the low DHA:EPA krill diet (0.27±0.03 mm d-1) or blended diet (0.29±0.02 mm d-1). Tissue turnover in salmon, measured in half-lives, was 5 to 28 days for essential fatty acids, and 9 to 184 days for bulk isotopes of nitrogen and carbon, indicating that predator tissue fatty acids reflect diet sooner than stable isotopes. After the rearing experiment, salmon were starved for 4 weeks and their critical swimming speeds measured to determine whether nutritional history had an affect on aerobic performance. Although there were no significant differences in swim performance among diet treatments, there was a significant relationship (r2=0.57, p=0.02) between swimming speed and an individual's size and storage lipids across diet treatments. Results from this study will support future ecological studies of migrating juvenile salmon and quantitative estimates of diet in other anadromous fish.

  1. 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)

  2. High-intensity interval training and β-hydroxy-β-methylbutyric free acid improves aerobic power and metabolic thresholds

    Science.gov (United States)

    2014-01-01

    Background Previous research combining Calcium β-hydroxy-β-methylbutyrate (CaHMB) and running high-intensity interval training (HIIT) have shown positive effects on aerobic performance measures. The purpose of this study was to examine the effect of β-hydroxy-β-methylbutyric free acid (HMBFA) and cycle ergometry HIIT on maximal oxygen consumption (VO2peak), ventilatory threshold (VT), respiratory compensation point (RCP) and time to exhaustion (Tmax) in college-aged men and women. Methods Thirty-four healthy men and women (Age: 22.7 ± 3.1 yrs ; VO2peak: 39.3 ± 5.0 ml · kg-1 · min-1) volunteered to participate in this double-blind, placebo-controlled design study. All participants completed a series of tests prior to and following treatment. A peak oxygen consumption test was performed on a cycle ergometer to assess VO2peak, Tmax, VT, and RCP. Twenty-six participants were randomly assigned into either a placebo (PLA-HIIT) or 3 g per day of HMBFA (BetaTor™) (HMBFA-HIIT) group. Eight participants served as controls (CTL). Participants in the HIIT groups completed 12 HIIT (80-120% maximal workload) exercise sessions consisting of 5–6 bouts of a 2:1 minute cycling work to rest ratio protocol over a four-week period. Body composition was measured with dual energy x-ray absorptiometry (DEXA). Outcomes were assessed by ANCOVA with posttest means adjusted for pretest differences. Results The HMBFA-HIIT intervention showed significant (p HIIT group. Both PLA-HIIT and HMBFA-HIIT treatment groups demonstrated significant (p HIIT and HMBFA-HIIT groups. Conclusions Our findings support the use of HIIT in combination with HMBFA to improve aerobic fitness in college age men and women. These data suggest that the addition of HMBFA supplementation may result in greater changes in VO2peak and VT than HIIT alone. Study registration The study was registered on ClinicalTrials.gov (ID NCT01941368). PMID:24782684

  3. Production of 4-Hydroxybenzoic Acid by an Aerobic Growth-Arrested Bioprocess Using Metabolically Engineered Corynebacterium glutamicum.

    Science.gov (United States)

    Kitade, Yukihiro; Hashimoto, Ryoma; Suda, Masako; Hiraga, Kazumi; Inui, Masayuki

    2018-03-15

    Corynebacterium glutamicum was metabolically engineered to produce 4-hydroxybenzoic acid (4-HBA), a valuable aromatic compound used as a raw material for the production of liquid crystal polymers and paraben. C. glutamicum was found to have a higher tolerance to 4-HBA toxicity than previously reported hosts used for the production of genetically engineered 4-HBA. To obtain higher titers of 4-HBA, we employed a stepwise overexpression of all seven target genes in the shikimate pathway in C. glutamicum Specifically, multiple chromosomal integrations of a mutated aroG gene from Escherichia coli , encoding a 3-deoxy-d-arabinoheptulosonic acid 7-phosphate (DAHP) synthase, and wild-type aroCKB from C. glutamicum , encoding chorismate synthase, shikimate kinase, and 3-dehydroquinate synthase, were effective in increasing product titers. The last step of the 4-HBA biosynthesis pathway was recreated in C. glutamicum by expressing a highly 4-HBA-resistant chorismate pyruvate-lyase (UbiC) from the intestinal bacterium Providencia rustigianii To enhance the yield of 4-HBA, we reduced the formation of by-products, such as 1,3-dihydroxyacetone and pyruvate, by deleting hdpA , a gene coding for a haloacid dehalogenase superfamily phosphatase, and pyk , a gene coding for a pyruvate kinase, from the bacterial chromosome. The maximum concentration of 4-HBA produced by the resultant strain was 36.6 g/liter, with a yield of 41% (mol/mol) glucose after incubation for 24 h in minimal medium in an aerobic growth-arrested bioprocess using a jar fermentor. To our knowledge, this is the highest concentration of 4-HBA produced by a metabolically engineered microorganism ever reported. IMPORTANCE Since aromatic compound 4-HBA has been chemically produced from petroleum-derived phenol for a long time, eco-friendly bioproduction of 4-HBA from biomass resources is desired in order to address environmental issues. In microbial chemical production, product toxicity often causes problems, but we

  4. Biodegradation of industrial-strength 2,4-dichlorophenoxyacetic acid wastewaters in the presence of glucose in aerobic and anaerobic sequencing batch reactors.

    Science.gov (United States)

    Elefsiniotis, Panagiotis; Wareham, David G

    2013-01-01

    This research explored the biodegradability of 2,4-dichlorophenoxyacetic acid (2,4-D) in two laboratory-scale sequencing batch reactors (SBRs) that operated under aerobic and anaerobic conditions. The potential limit of 2,4-D degradation was investigated at a hydraulic retention time of 48 h, using glucose as a supplemental substrate and increasing feed concentrations of 2,4-D; namely 100 to 700 mg/L (i.e. industrial strength) for the aerobic system and 100 to 300 mg/L for the anaerobic SBR. The results revealed that 100 mg/L of 2,4-D was completely degraded following an acclimation period of 29 d (aerobic SBR) and 70 d (anaerobic SBR). The aerobic system achieved total 2,4-D removal at feed concentrations up to 600 mg/L which appeared to be a practical limit, since a further increase to 700 mg/L impaired glucose degradation while 2,4-D biodegradation was non-existent. In all cases, glucose was consumed before the onset of 2,4-D degradation. In the anaerobic SBR, 2,4-D degradation was limited to 120 mg/L.

  5. Nicotine Nasal Spray

    Science.gov (United States)

    Nicotine nasal spray is used to help people stop smoking. Nicotine nasal spray should be used together with a ... support groups, counseling, or specific behavior change techniques. Nicotine nasal spray is in a class of medications ...

  6. 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 ...

  7. Nicotine Oral Inhalation

    Science.gov (United States)

    Nicotine oral inhalation is used to help people stop smoking. Nicotine oral inhalation should be used together with a ... support groups, counseling, or specific behavioral change techniques. Nicotine inhalation is in a class of medications called ...

  8. Cross-reactivity of acid-sensing ion channel and Na⁺-H⁺ exchanger antagonists with nicotinic acetylcholine receptors.

    Science.gov (United States)

    Santos-Torres, Julio; Ślimak, Marta A; Auer, Sebastian; Ibañez-Tallon, Inés

    2011-11-01

    Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the mammalian central and peripheral nervous systems, where they contribute to neuronal excitability and synaptic communication. It has been reported that nAChRs are modulated by BK channels and that BK channels, in turn, are inhibited by acid-sensing ion channels (ASICs). Here we investigate the possible functional interaction between these channels in medial habenula (MHb) neurones. We report that selective antagonists of large-conductance calcium-activated potassium channels and ASIC1a channels, paxilline and psalmotoxin 1, respectively, did not induce detectable changes in nicotine-evoked currents. In contrast, the non-selective ASIC and Na(+)-H(+) exchanger (NHE1) antagonists, amiloride and its analogues, suppressed nicotine-evoked responses in MHb neurones of wild-type and ASIC2 null mice, excluding a possible involvement of ASIC2 in the nAChR inhibition by amiloride. Zoniporide, a more selective inhibitor of NHE1, reversibly inhibited α3β4-, α7- and α4-containing (*) nAChRs in Xenopus oocytes and in brain slices, as well as in PS120 cells deficient in NHE1 and virally transduced with nAChRs, suggesting a generalized effect of zoniporide in most neuronal nAChR subtypes. Independently from nAChR antagonism, zoniporide profoundly blocked synaptic transmission onto MHb neurones without affecting glutamatergic and GABA receptors. Taken together, these results indicate that amiloride and zoniporide, which are clinically used to treat hypertension and cardiovascular disease, have an inhibitory effect on neuronal nAChRs when used experimentally at high doses. The possible cross-reactivity of these compounds with nAChRs in vivo will require further investigation.

  9. 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...... with the hypothesis that adipose tissue vasodilation during exercise is secondary to metabolic events connected to lipolysis....

  10. Lactic Acid Bacteria in Total Mixed Ration Silage Containing Soybean Curd Residue: Their Isolation, Identification and Ability to Inhibit Aerobic Deterioration

    Science.gov (United States)

    Li, Y.; Wang, F.; Nishino, N.

    2016-01-01

    We investigated the effects of the predominant lactic acid bacteria (LAB) on the fermentation characteristics and aerobic stability of total mixed ration (TMR) silage containing soybean curd residue (SC-TMR silage). The SC-TMR materials were ensiled in laboratory silos for 14 or 56 days. LAB predominant in SC-TMR silage were identified (Exp. 1). Lactobacillus fermentum (L. fermentum) and Streptococcus bovis (S. bovis) were found in the untreated materials, Leuconostoc pseudomesenteroides (L. pseudomesenteroides) in 14-day silage and Lactobacillus plantarum (L. plantarum) in all silages. Pediococcus acidilactici (P. acidilactici), Lactobacillus paracasei (L. paracasei), and Lactobacillus brevis (L. brevis) formed more than 90% of the isolates in 56-day silage. Italian ryegrass and whole crop maize were inoculated with P. acidilactici and L. brevis isolates and the fermentation and aerobic stability determined (Exp. 2). Inoculation with P. acidilactici and L. brevis alone or combined improved the fermentation products in ryegrass silage and markedly enhanced its aerobic stability. In maize silage, P. acidilactici and L. brevis inoculation caused no changes and suppressed deterioration when combined with increases in acetic acid content. The results indicate that P. acidilactici and L. brevis may produce a synergistic effect to inhibit SC-TMR silage deterioration. Further studies are needed to identify the inhibitory substances, which may be useful for developing potential antifungal agents. PMID:26949952

  11. Lactic Acid Bacteria in Total Mixed Ration Silage Containing Soybean Curd Residue: Their Isolation, Identification and Ability to Inhibit Aerobic Deterioration

    Directory of Open Access Journals (Sweden)

    Y. Li

    2016-04-01

    Full Text Available We investigated the effects of the predominant lactic acid bacteria (LAB on the fermentation characteristics and aerobic stability of total mixed ration (TMR silage containing soybean curd residue (SC-TMR silage. The SC-TMR materials were ensiled in laboratory silos for 14 or 56 days. LAB predominant in SC-TMR silage were identified (Exp. 1. Lactobacillus fermentum (L. fermentum and Streptococcus bovis (S. bovis were found in the untreated materials, Leuconostoc pseudomesenteroides (L. pseudomesenteroides in 14-day silage and Lactobacillus plantarum (L. plantarum in all silages. Pediococcus acidilactici (P. acidilactici, Lactobacillus paracasei (L. paracasei, and Lactobacillus brevis (L. brevis formed more than 90% of the isolates in 56-day silage. Italian ryegrass and whole crop maize were inoculated with P. acidilactici and L. brevis isolates and the fermentation and aerobic stability determined (Exp. 2. Inoculation with P. acidilactici and L. brevis alone or combined improved the fermentation products in ryegrass silage and markedly enhanced its aerobic stability. In maize silage, P. acidilactici and L. brevis inoculation caused no changes and suppressed deterioration when combined with increases in acetic acid content. The results indicate that P. acidilactici and L. brevis may produce a synergistic effect to inhibit SC-TMR silage deterioration. Further studies are needed to identify the inhibitory substances, which may be useful for developing potential antifungal agents.

  12. 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

  13. 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.

  14. Effects of 5 Thio-D-Glucose on cellular adenosine triphosphate levels and deoxyribonucleic acid rejoining in hypoxic and aerobic Chinese hamster cells

    International Nuclear Information System (INIS)

    Nagle, W.A.; Moss, A.J. Jr.; Roberts, H.G. Jr.; Baker, M.L.

    1980-01-01

    Intracellular adenosine triphosphate (ATP) levels were measured in both hypoxic and aerobic cultures of V79 Chinese hamster cells treated with 5-thio-D-glucose (5-SH-D-Glc). This glucose analog, a known inhibitor of D-glucose transport and metabolism, reduced ATP in cell cultures allowed to become hypoxic by cell metabolism, but not in aerobic cultures treated similarly. Cells depleted of ATP were unable to rejoin x-ray induced deoxyribonucleic acid (DNA) strand breaks as measured by the alkaline sucrose gradient sedimentation technique. The inference for radiation therapy is that inhibition of glucose metabolism selectively depletes energy reserves in hypoxic cells, rendering these cells more radiosensitive and leading to a more effective tumor treatment

  15. 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.

  16. Passive immunization against nicotine attenuates nicotine discrimination.

    Science.gov (United States)

    Malin, David H; Alvarado, Candice L; Woodhouse, Katherine S; Karp, Hilary; Urdiales, Evelyn; Lay, Diana; Appleby, Phillip; Moon, William D; Ennifar, Sofiane; Basham, Lisa; Fattom, Ali

    2002-04-26

    Ten rats were trained in a two lever operant chamber to press different levers after a nicotine injection (0.14 mg/kg s.c.) or a saline injection on an FR10 schedule. The rats were then injected i.p. with either 150 mg nicotine-specific IgG or the same amount of control IgG from non-immunized rabbits. On successive days, they were retested with both levers active after a saline injection, a full training dose of nicotine and a half dose of nicotine (0.07 mg/kg s.c.). After saline injection, both groups pressed the saline lever almost exclusively. After each of the nicotine doses, the immunized rats performed a significantly lower percentage of their lever presses on the nicotine lever than did non-immunized rats. The results suggest that passive immunization can interfere with the stimulus properties of nicotine.

  17. Nicotine's defensive function in nature.

    Directory of Open Access Journals (Sweden)

    Anke Steppuhn

    2004-08-01

    Full Text Available Plants produce metabolites that directly decrease herbivore performance, and as a consequence, herbivores are selected for resistance to these metabolites. To determine whether these metabolites actually function as defenses requires measuring the performance of plants that are altered only in the production of a certain metabolite. To date, the defensive value of most plant resistance traits has not been demonstrated in nature. We transformed native tobacco(Nicotiana attenuata with a consensus fragment of its two putrescine N-methyl transferase (pmt genes in either antisense or inverted-repeat (IRpmt orientations. Only the latter reduced (by greater than 95% constitutive and inducible nicotine. With D(4-nicotinic acid (NA, we demonstrate that silencing pmt inhibits nicotine production, while the excess NA dimerizes to form anatabine. Larvae of the nicotine-adapted herbivore Manduca sexta (tobacco hornworm grew faster and, like the beetle Diabrotica undecimpunctata, preferred IRpmt plants in choice tests. When planted in their native habitat, IRpmt plants were attacked more frequently and, compared to wild-type plants, lost 3-fold more leaf area from a variety of native herbivores, of which the beet armyworm, Spodoptera exigua, and Trimerotropis spp. grasshoppers caused the most damage. These results provide strong evidence that nicotine functions as an efficient defense in nature and highlights the value of transgenic techniques for ecological research.

  18. Transformation of Unsaturated Fatty Acids/Esters to Corresponding Keto Fatty Acids/Esters by Aerobic Oxidation with Pd(II)/Lewis Acid Catalyst.

    Science.gov (United States)

    Senan, Ahmed M; Zhang, Sicheng; Zeng, Miao; Chen, Zhuqi; Yin, Guochuan

    2017-08-16

    Utilization of renewable biomass to partly replace the fossil resources in industrial applications has attracted attention due to the limited fossil feedstock with the increased environmental concerns. This work introduced a modified Wacker-type oxidation for transformation of unsaturated fatty acids/esters to the corresponding keto fatty acids/esters, in which Cu 2+ cation was replaced with common nonredox metal ions, that is, a novel Pd(II)/Lewis acid (LA) catalyst. It was found that adding nonredox metal ions can effectively promote Pd(II)-catalyzed oxidation of unsaturated fatty acids/esters to the corresponding keto fatty acids/esters, even much better than Cu 2+ , and the promotional effect is highly dependent on the Lewis acidity of added nonredox metal ions. The improved catalytic efficiency is attributed to the formation of heterobimetallic Pd(II)/LA species, and the oxidation mechanism of this Pd(II)/LA catalyst is also briefly discussed.

  19. Effect of deboning time on the growth of Salmonella, E. coli, aerobic, and lactic acid bacteria during beef sausage processing and storage.

    Science.gov (United States)

    Sukumaran, Anuraj T; Holtcamp, Alexander J; Englishbey, April K; Campbell, Yan L; Kim, Taejo; Schilling, Mark W; Dinh, Thu T N

    2018-05-01

    The objective of the current study was to determine the effects of deboning time, three steps of sausage processing (grinding, salting, and batter formulation), and storage time (of raw materials and cooked sausage) on the growth (log CFU/g) of aerobic bacteria, lactic acid bacteria, and inoculated Salmonella and E. coli. Beef deboning time did not influence bacterial counts (P≥0.138). However, salting of raw ground beef resulted in a 0.4-log reduction in both aerobic plate count (APC) and Salmonella (P≤0.001). Lactic acid bacteria were increased from non-detectable concentration (0.54 log) on d 0 to 3.8 log on d 120 of vacuum storage (P≤0.019). Salmonella counts were increased (P<0.001) over storage time (3.2 to 3.3 log CFU/g from d 0 to 10). Results indicated that salting and batter formulation had a greater impact on bacterial counts than rigor state of raw beef. Published by Elsevier Ltd.

  20. Highly efficient treatment of aerobic vaginitis with simple acidic buffered gels: The importance of pH and buffers on the microenvironment of vaginas.

    Science.gov (United States)

    Sun, Xiaodong; Qiu, Haiying; Jin, Yiguang

    2017-06-15

    Aerobic vaginitis (AV) leads to uterus deep infection or preterm birth. Antibacterial agents are not optimal therapeutics of AV. Here, we report a series of temperature-sensitive in situ forming acidic buffered gels for topical treatment of AV, involving lactate, acetate, and citrate gels at pH 3.5, 5.0, and 6.5. AV rat models were prepared following vaginal infection with Staphylococcus aureus and Escherichia coli. In vitro/in vivo studies of the buffered gels were performed compared with ofloxacin gels and blank gels. All the buffered gels showed the lower in vitro antibacterial activities than ofloxacin gels but the better in vivo anti-S. aureus effects and similar anti-E. coli effects. The buffered gels improved Lactobacillus growth in the vaginas. Both the healthy rat vaginal pH and the pH of rat vaginas treated with the buffered gels were about 6.5 though the AV rat models or ones treated with ofloxacin gels still remained at the high pH more than 7.0. After treatments with the buffered gels, the vaginal smears changed to a clean state nearly without aerobic bacteria, the vaginal tissues were refreshed, and the immunoreactions were downregulated. The acidic buffered gels bring rapid decrease of local vaginal pH, high antibacterial activities, improvement of probiotics, and alleviation of inflammation. They are simple, highly efficient, and safe anti-AV formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Two new Ni(II) supramolecular complexes based on ethyl isonicotinate and ethyl nicotinate for removal of acid blue 92 dye

    Science.gov (United States)

    Etaiw, Safaa El-din H.; Marie, Hassan

    2018-03-01

    Two new luminescent supramolecular complexes (SC); [Ni(EIN)4(NCS)2] SC1 and [Ni2(EN)8(NCS)4] SC2, (EIN = ethyl isonicotinate, EN = ethyl nicotinate), have been synthesized by self-assembly method and structurally characterized by X-ray single crystal, FT-IR and UV-Vis spectra, PXRD, elemental and thermogravimetric analyses. Both SC1 and SC2 are monoclinic crystals however, they have different asymmetric units. Ni(II) atoms in both SC are isostructural and have similar hexa-coordinate environment. The structures of SC1 and SC2 consist of parallel polymeric 1D-chains, extended in two and three dimensional supramolecular frameworks by intermolecular hydrogen bonding interactions. SC1 and SC2 are luminescent materials which can be used in applications as molecular sensing systems. SC1 and SC2 were used as heterogeneous catalysts for degradation of acid blue 92 (AB-92) under sun light irradiation. The fluorescence measurements of terephthalic acid technique as a probe molecule were used to determine the •OH radicals. Also the radicals trapping experiments using isopropanol alcohol (IPA) as radical scavenger were discussed. In addition a mechanism of degradation was proposed and discussed.

  2. Effects of gene-augmentation on the formation, characteristics and microbial community of 2,4-dichlorophenoxyacetic acid degrading aerobic microbial granules

    Energy Technology Data Exchange (ETDEWEB)

    Quan, Xiang-chun, E-mail: xchquan@yahoo.com.cn [Key Laboratory of Water and Sediment Sciences of Ministry of Education/State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875 (China); Ma, Jing-yun; Xiong, Wei-cong; Yang, Zhi-feng [Key Laboratory of Water and Sediment Sciences of Ministry of Education/State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875 (China)

    2011-11-30

    Highlights: Black-Right-Pointing-Pointer The first study to cultivate aerobic granules capable of utilizing 2,4-D as the sole carbon source. Black-Right-Pointing-Pointer Granules cultivated through gene-augmentation were first compared systematically with the control on granule formation, degradation kinetics, morphology, and microbial community. Black-Right-Pointing-Pointer The first report on the fate of transconjugats in the granules during long term operation after bioaugmentation. Black-Right-Pointing-Pointer The first study to isolate in dominant bacteria in 2,4-D degrading microbial granules. - Abstract: Development of 2,4-dichlorophenoxyacetic acid (2,4-D) degrading aerobic granular sludge was conducted in two sequencing batch reactors (SBR) with one bioaugmented with a plasmid pJP4 donor strain Pseudomonas putida SM1443 and the other as a control. Half-matured aerobic granules pre-grown on glucose were used as the starting seeds and a two-stage operation strategy was applied. Granules capable of utilizing 2,4-D (about 500 mg/L) as the sole carbon source was successfully cultivated in both reactors. Gene-augmentation resulted in the enhancement of 2,4-D degradation rates by the percentage of 65-135% for the granules on Day 18, and 6-24% for the granules on Day 105. Transconjugants receiving plasmid pJP4 were established in the granule microbial community after bioaugmentation and persisted till the end of operation. Compared with the control granules, the granules in the bioaugmented reactor demonstrated a better settling ability, larger size, more abundant microbial diversity and stronger tolerance to 2,4-D. The finally obtained granules in the bioaugmented and control reactor had a granule size of around 600 {mu}m and 500 {mu}m, a Shannon-Weaver diversity index (H) of 0.96 and 0.55, respectively. A shift in microbial community was found during the granulation process.

  3. Effects of gene-augmentation on the formation, characteristics and microbial community of 2,4-dichlorophenoxyacetic acid degrading aerobic microbial granules.

    Science.gov (United States)

    Quan, Xiang-chun; Ma, Jing-yun; Xiong, Wei-cong; Yang, Zhi-feng

    2011-11-30

    Development of 2,4-dichlorophenoxyacetic acid (2,4-D) degrading aerobic granular sludge was conducted in two sequencing batch reactors (SBR) with one bioaugmented with a plasmid pJP4 donor strain Pseudomonas putida SM1443 and the other as a control. Half-matured aerobic granules pre-grown on glucose were used as the starting seeds and a two-stage operation strategy was applied. Granules capable of utilizing 2,4-D (about 500 mg/L) as the sole carbon source was successfully cultivated in both reactors. Gene-augmentation resulted in the enhancement of 2,4-D degradation rates by the percentage of 65-135% for the granules on Day 18, and 6-24% for the granules on Day 105. Transconjugants receiving plasmid pJP4 were established in the granule microbial community after bioaugmentation and persisted till the end of operation. Compared with the control granules, the granules in the bioaugmented reactor demonstrated a better settling ability, larger size, more abundant microbial diversity and stronger tolerance to 2,4-D. The finally obtained granules in the bioaugmented and control reactor had a granule size of around 600 μm and 500 μm, a Shannon-Weaver diversity index (H) of 0.96 and 0.55, respectively. A shift in microbial community was found during the granulation process. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Bioaugmentation of half-matured granular sludge with special microbial culture promoted establishment of 2,4-dichlorophenoxyacetic acid degrading aerobic granules.

    Science.gov (United States)

    Quan, Xiangchun; Ma, Jingyun; Xiong, Weicong; Wang, Xinrui

    2015-06-01

    Aerobic granular sludge degrading recalcitrant compounds are generally hard to be cultivated. This study investigated the feasibility of cultivating 2,4-dichlorophenoxyacetic acid (2,4-D) degrading aerobic granules using half-matured sludge granules pre-grown on glucose as the seeds and bioaugmentation with a 2,4-D degrading strain Achromobacter sp. QXH. Results showed that bioaugmentation promoted the steady transformation of glucose-grown granules to 2,4-D degrading sludge granules and fast establishment of 2,4-D degradation ability. The 2,4-D degradation rate of the bioaugmented granules was enhanced by 36-62 % compared to the control at 2,4-D concentrations of 144-565 mg/L on Day 18. The inoculated strain was incorporated into the half-matured granules successfully and survived till the end of operation (220 days). Sludge granules at a mean size of 420 µm and capable of utilizing 500 mg/L 2,4-D as the sole carbon source were finally obtained. Sludge microbial community shifted slightly during the whole operation and the dominant bacteria species belonged to Proteobacteria.

  5. 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.

  6. ENHANCED NITRILASE PRODUCTION BY RHODOCOCCUS PYRIDINIVORANS SN2 USING AN OPTIMIZED BIPHASIC FERMENTATION APPROACH AND ITS USE FOR NICOTINIC ACID SYNTHESIS

    Directory of Open Access Journals (Sweden)

    Karthikeya Kameswaran

    2014-12-01

    Full Text Available In the present study, nitrilase activity of Rhodococcus pyridinivorans SN2 was optimized by a combination of response surface methodology and biphasic fed batch strategy. The optimized conditions were 15 g l-1 of yeast extract and 6 g l-1 of benzonitrile (in feeds of 1 g l-1, followed by a feed of 10 g l-1 fructose and 4 g l-1 �-caprolactam leading to a biomass yield of 10±1 gdcw l-1 in 48 h with nitrilase activity of 150±20 U gdcw -1 and a nitrilase productivity of around 1500 U l-1. This represented a 16 fold increase in nitrilase productivity from 90 U l-1 under unoptimized conditions. Whole cells (2 gdcw of Rhodococcus pyridinivorans SN2 when immobilized in calcium alginate beads completely hydrolysed 10.5 g 3-cyanopyridine (~0.1 mol to nicotinic acid in 6.5 hours using a fed batch reaction at a scale of 100 ml.

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

    Directory of Open Access Journals (Sweden)

    Reka Tienken

    2015-09-01

    Full Text Available 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 energy to cows which were similar in body condition score had only minor effects on periparturient immune system function and the metabolism of those cows.

  8. Ruthenium-catalyzed aerobic oxidative decarboxylation of amino acids: a green, zero-waste route to biobased nitriles.

    Science.gov (United States)

    Claes, Laurens; Verduyckt, Jasper; Stassen, Ivo; Lagrain, Bert; De Vos, Dirk E

    2015-04-18

    Oxidative decarboxylation of amino acids into nitriles was performed using molecular oxygen as terminal oxidant and a heterogeneous ruthenium hydroxide-based catalyst. A range of amino acids was oxidized in very good yield, using water as the solvent.

  9. 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.

  10. [(3)H]Epibatidine photolabels non-equivalent amino acids in the agonist binding site of Torpedo and alpha4beta2 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Srivastava, Shouryadeep; Hamouda, Ayman K; Pandhare, Akash; Duddempudi, Phaneendra K; Sanghvi, Mitesh; Cohen, Jonathan B; Blanton, Michael P

    2009-09-11

    Nicotinic acetylcholine receptor (nAChR) agonists, such as epibatidine and its molecular derivatives, are potential therapeutic agents for a variety of neurological disorders. In order to identify determinants for subtype-selective agonist binding, it is important to determine whether an agonist binds in a common orientation in different nAChR subtypes. To compare the mode of binding of epibatidine in a muscle and a neuronal nAChR, we photolabeled Torpedo alpha(2)betagammadelta and expressed human alpha4beta2 nAChRs with [(3)H]epibatidine and identified by Edman degradation the photolabeled amino acids. Irradiation at 254 nm resulted in photolabeling of alphaTyr(198) in agonist binding site Segment C of the principal (+) face in both alpha subunits and of gammaLeu(109) and gammaTyr(117) in Segment E of the complementary (-) face, with no labeling detected in the delta subunit. For affinity-purified alpha4beta2 nAChRs, [(3)H]epibatidine photolabeled alpha4Tyr(195) (equivalent to Torpedo alphaTyr(190)) in Segment C as well as beta2Val(111) and beta2Ser(113) in Segment E (equivalent to Torpedo gammaLeu(109) and gammaTyr(111), respectively). Consideration of the location of the photolabeled amino acids in homology models of the nAChRs based upon the acetylcholine-binding protein structure and the results of ligand docking simulations suggests that epibatidine binds in a single preferred orientation within the alpha-gamma transmitter binding site, whereas it binds in two distinct orientations in the alpha4beta2 nAChR.

  11. [3H]Epibatidine Photolabels Non-equivalent Amino Acids in the Agonist Binding Site of Torpedo and α4β2 Nicotinic Acetylcholine Receptors*

    Science.gov (United States)

    Srivastava, Shouryadeep; Hamouda, Ayman K.; Pandhare, Akash; Duddempudi, Phaneendra K.; Sanghvi, Mitesh; Cohen, Jonathan B.; Blanton, Michael P.

    2009-01-01

    Nicotinic acetylcholine receptor (nAChR) agonists, such as epibatidine and its molecular derivatives, are potential therapeutic agents for a variety of neurological disorders. In order to identify determinants for subtype-selective agonist binding, it is important to determine whether an agonist binds in a common orientation in different nAChR subtypes. To compare the mode of binding of epibatidine in a muscle and a neuronal nAChR, we photolabeled Torpedo α2βγδ and expressed human α4β2 nAChRs with [3H]epibatidine and identified by Edman degradation the photolabeled amino acids. Irradiation at 254 nm resulted in photolabeling of αTyr198 in agonist binding site Segment C of the principal (+) face in both α subunits and of γLeu109 and γTyr117 in Segment E of the complementary (−) face, with no labeling detected in the δ subunit. For affinity-purified α4β2 nAChRs, [3H]epibatidine photolabeled α4Tyr195 (equivalent to Torpedo αTyr190) in Segment C as well as β2Val111 and β2Ser113 in Segment E (equivalent to Torpedo γLeu109 and γTyr111, respectively). Consideration of the location of the photolabeled amino acids in homology models of the nAChRs based upon the acetylcholine-binding protein structure and the results of ligand docking simulations suggests that epibatidine binds in a single preferred orientation within the α-γ transmitter binding site, whereas it binds in two distinct orientations in the α4β2 nAChR. PMID:19620239

  12. A three amino acid deletion in the transmembrane domain of the nicotinic acetylcholine receptor α6 subunit confers high-level resistance to spinosad in Plutella xylostella.

    Science.gov (United States)

    Wang, Jing; Wang, Xingliang; Lansdell, Stuart J; Zhang, Jianheng; Millar, Neil S; Wu, Yidong

    2016-04-01

    Spinosad is a macrocyclic lactone insecticide that acts primarily at the nicotinic acetylcholine receptors (nAChRs) of target insects. Here we describe evidence that high levels of resistance to spinosad in the diamondback moth (Plutella xylostella) are associated with a three amino acid (3-aa) deletion in the fourth transmembrane domain (TM4) of the nAChR α6 subunit (Pxα6). Following laboratory selection with spinosad, the SZ-SpinR strain of P. xylostella exhibited 940-fold resistance to spinosad. In addition, the selected insect population had 1060-fold cross-resistance to spinetoram but, in contrast, no cross-resistance to abamectin was observed. Genetic analysis indicates that spinosad resistance in SZ-SpinR is inherited as a recessive and autosomal trait, and that the 3-aa deletion (IIA) in TM4 of Pxα6 is tightly linked to spinosad resistance. Because of well-established difficulties in functional expression of cloned insect nAChRs, the analogous resistance-associated deletion mutation was introduced into a prototype nAChR (the cloned human α7 subunit). Two-electrode voltage-clamp recording with wild-type and mutated nAChRs expressed in Xenopus laevis oocytes indicated that the mutation causes a complete loss of agonist activation. In addition, radioligand binding studies indicated that the 3-aa deletion resulted in significantly lower-affinity binding of the extracellular neurotransmitter-binding site. These findings are consistent with the 3-amino acid (IIA) deletion within the transmembrane domain of Pxα6 being responsible for target-site resistance to spinosad in the SZ-SpinR strain of P. xylostella. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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    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.

  14. Nicotine Effects on the Impact of Stress

    Science.gov (United States)

    2016-03-01

    administration ceased: nicotine may have some beneficial effects, but nicotine withdrawal is unambiguously detrimental. Our funding period ended on...effects of nicotine . Our research involves a model of nicotine use (voluntary intravenous self- administration of nicotine in rats) and PTSD (fear... nicotine or nicotine withdrawal affect the development of conditioned fear under circumstances where nicotine self- administration is discontinued

  15. Effect of 12 weeks aerobic exercise for along with folic acid supplementation on the levels of the ghrelin hormone amount of food intake and weight changes of female Wistar rats

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    A Parvizi

    2016-11-01

    Full Text Available Background & aim: Results of numerous studies have shown that approximately 1 to 78 percent of female athletes suffer from eating disorders. On the other hand, it has been mentioned that folic acid could increase appetite. The ghrelin hormone is known as a strong stimulant for appetite. Therefore, to clarify the role of exercise and food intake of folic acid on plasma acylated ghrelin the study aim was to evaluate the effect of 12 weeks of aerobic training on ghrelin supplementation of folic acid and quantity of food intake and weight change in female rats. Methods: In the present experimental study, 24 rats were randomly divided into three groups of 8 including: control, training and training along with folic acid supplementation. The training protocol consisted of aerobic exercise running on a treadmill for 12 weeks (5 days a week. Standard meal and water were freely provided for the subjects and in the supplement group 10 mg dissolved folic acid per liter of water were used and then the food intake and body weight was measured every week. 24 hours after the last session of training and 8 hours of overnight fasting, blood and tissue samples were collected and hormones levels were measured using Eliza method. To data analyzing, one way ANOVA and Tukey post hoc test was used. Results: The results showed that 12 weeks of  aerobic training with folic acid supplementation had significantly reduced serum acylated ghrelin levels (P0.05. The 12-week aerobic training with folic acid intake in comparison with other groups significantly increased food intake and body weight gain (p < 0.05. Conclusion: According to the acylated ghrelin reduction and lack of change in the stomach acylated ghrelin with increased food intake and body weight in rats, it seems that taking folic acid supplements inactive athletes with another strong mechanism, increasing consumption of food and influence on appetite center.

  16. Changes in lipid metabolism and β-adrenergic response of adipose tissues of periparturient dairy cows affected by an energy-dense diet and nicotinic acid supplementation.

    Science.gov (United States)

    Kenéz, Á; Tienken, R; Locher, L; Meyer, U; Rizk, A; Rehage, J; Dänicke, S; Huber, K

    2015-08-01

    Dairy cattle will mobilize large amounts of body fat during early lactation as an effect of decreased lipogenesis and increased lipolysis. Regulation of lipid metabolism involves fatty acid synthesis from acetate and β-adrenergic-stimulated phosphorylation of hormone-sensitive lipase (HSL) and perilipin in adipocytes. Although basic mechanisms of mobilizing fat storage in transition cows are understood, we lack a sufficiently detailed understanding to declare the exact regulatory network of these in a broad range of dairy cattle. The objective of the present study was to quantify 1) protein abundance of fatty acid synthase (FAS), 2) extent of phosphorylation of HSL and perilipin in vivo, and 3) β-adrenergic stimulated lipolytic response of adipose tissues in vitro at different stages of the periparturient period. We fed 20 German Holstein cows an energy-dense or an energetically adequate diet prepartum and 0 or 24 g/d nicotinic acid (NA) supplementation. Biopsy samples of subcutaneous and retroperitoneal adipose tissue were obtained at d 42 prepartum (d -42) and at d 1, 21, and 100 postpartum (d +1, d +21, d +100, respectively). To assess β-adrenergic response, tissue samples were incubated with 1 μ isoproterenol for 90 min at 37°C. The NEFA and glycerol release, as well as HSL and perilipin phosphorylation, was measured as indicators of in vitro stimulated lipolysis. In addition, protein expression of FAS and extent of HSL and perilipin phosphorylation were measured in fresh, nonincubated samples. There was no effect of dietary energy density or NA on the observed variables. The extent of HSL and perilipin phosphorylation under isoproterenol stimulation was strongly correlated with the release of NEFA and glycerol, consistent with the functional link between β-adrenergic-stimulated protein phosphorylation and lipolysis. In the nonincubated samples, FAS protein expression was decreased at d +1 and d +21, whereas HSL and perilipin phosphorylation increased

  17. Electrochemical Performance of a Carbon Nanotube/La-Doped TiO2 Nanocomposite and its Use for Preparation of an Electrochemical Nicotinic Acid Sensor

    Directory of Open Access Journals (Sweden)

    Hanxing Liu

    2008-11-01

    Full Text Available A carbon nanotube/La-doped TiO2 (La-TiO2 nanocomposite (CLTN was prepared by a procedure similar to a complex/adsorption process. Scanning electron microscopy (SEM images show that the La-TiO2 distributes on the carbon nanotube walls. The CLTN was mixed with paraffin to form a CLTN paste for the CLTN paste electrode (CLTNPE. The electrochemical characteristics of CLTNPE were compared with that of conventional carbon electrodes such as the carbon paste electrode (CPE and glass carbon electrode (GC. The CLTNPE exhibits electrochemical activity and was used to investigate the electrochemistry of nicotinic acid (NA. The modified electrode has a strong electrocatalytic effect on the redox of NA. The cyclic voltammetry (CV redox potential of NA at the CLTNPE is 320 mV. The oxidation process of NA on the CLTNPE is pH dependent. A sensitive chronoamperometric response for NA was obtained covering a linear range from 1.0×10-6 mol·L-1 to 1.2×10-4 mol·L-1, with a detection limit of 2.7×10-7 mol·L-1. The NA sensor displays a remarkable sensitivity and stability. The mean recovery of NA in the human urine is 101.8%, with a mean variation coefficient (RSD of 2.6%.

  18. Aerobic decolorization and degradation of Acid Orange G (AOG) by suspended growing cells and immobilized cells of a yeast strain Candida tropicalis TL-F1.

    Science.gov (United States)

    Tan, Liang; Li, Hua; Ning, Shuxiang; Hao, Jia

    2014-10-01

    In this study, aerobic decolorization and degradation of azo dye Acid Orange G (AOG) by both suspended growing cells and immobilized cells of a yeast strain Candida tropicalis TL-F1 were studied. The effects of different parameters on decolorization of AOG by both growing suspended and immobilized strain TL-F1 were investigated. Furthermore, a possible decolorization mechanism of AOG was proposed through analyzing metabolic intermediates using UV-vis and high-performance liquid chromatography-mass spectrometry (HPLC-MS) methods. Strain TL-F1 could decolorize AOG in both liquid and solid mediums through degradation. The optimal conditions for decolorization with suspended growing cells of strain TL-F1 were as follows: 6-10 g/L sucrose, 5-7 g/L urea, ≥6 % (v/v) inoculation size, ≥160 rpm, 35-40 °C, and pH 5.0-6.0; and those for immobilized cells, the conditions were as follows: 4-6 g/L glucose, 0.2-0.4 g/L urea, 6-10 g/L (wet cell pellets) inoculation size, ≥160 rpm, 35-40 °C, and pH 5.0-7.0. Results of UV-vis scanning spectra suggested that AOG was decolorized through biodegradation, and the possible pathway was proposed through the results of HPLC-MS analysis and related literature. This is a systematic research on aerobic decolorization and degradation of AOG by both suspended and immobilized cells of a C. tropicalis strain.

  19. On complex compounds of molybdenum(5) with nicotinic amide, isonicotinic acid hydrazide and some of its derivatives

    International Nuclear Information System (INIS)

    Azizov, M.M.; Kushakbaev, A.; Parpiev, N.A.

    1977-01-01

    Oxychloride complexes of molybdenum (5) with polyfunctional ligands (L), namely with nicotinamide (NA), isonicotinic acid hydrazide (INH) and its derivatives (ftivazide, saluzide and larusan) have been synthesized and investigated. In ethanol all the ligands independently of their molar ratio form with MoCl 5 a non-electrolite compound MoOCl 3 xL 2 . Infrared spectra of the complexes suggest that in Mo(5) complexeS with NA and INH the central atom is bound through the pyridine nitrogen, whereas in the complexes with INH derivatives it is bound throught the carbonyl group oxygen

  20. 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.

  1. Interactions of nitric oxide with lipid peroxidation products under aerobic conditions: inhibitory effects on the formation of malondialdehyde and related thiobarbituric acid-reactive substances.

    Science.gov (United States)

    d'Ischia, M; Palumbo, A; Buzzo, F

    2000-02-01

    Under aerobic conditions, exposure of peroxidized lipids to nitric oxide (NO) was found to result in a rapid decrease in the levels of thiobarbituric acid-reactive substances (TBARS). Addition of 10-100 microM NO to rat brain homogenates preincubated for 2 h at 37 degrees C caused up to a 20% decrease in the levels of TBARS compared to controls. A similar inhibitory effect was observed on TBARS produced by Fe(2+)-induced decomposition of 15-hydroperoxyeicosatetraenoic acid (15-HPETE), due apparently to NO-induced decomposition of the hydroperoxide (ferrous oxidation/xylenol orange assay). Prostaglandin G(2) (PGG(2), 35 microM), as a model bicyclic endoperoxide, and malondialdehyde (MDA, 20 microM), the main component of TBARS, proved also susceptible to degradation by NO or NO donors (diethylamine NONOate, DEA/NO) at concentrations of 100 microM or higher in 0.05 M phosphate buffer, pH 7.4, and at 37 degrees C, as indicated by the reduced response to the TBA assay. No significant effect on TBARS determination was caused by nitrite ions. These and other data indicate that NO can inhibit TBARS formation by decomposing primary lipid peroxidation products, chiefly 15-HPETE and related hydroperoxides, and, to a lesser extent, later stage TBARS precursors, including bicyclic endoperoxides and MDA, via nitrosation and other oxidative routes, without however affecting chromogenic reactions during the assay. Copyright 2000 Academic Press.

  2. Cigarette nicotine yields and nicotine intake among Japanese male workers

    OpenAIRE

    Ueda, K; Kawachi, I; Nakamura, M; Nogami, H; Shirokawa, N; Masui, S; Okayama, A; Oshima, A

    2002-01-01

    Objectives: To analyse brand nicotine yield including "ultra low" brands (that is, cigarettes yielding ≤ 0.1 mg of nicotine by Federal Trade Commission (FTC) methods) in relation to nicotine intake (urinary nicotine, cotinine and trans-3'-hydroxycotinine) among 246 Japanese male smokers.

  3. Formation of a cobalt(III)-phenoxyl radical complex by acetic acid promoted aerobic oxidation of a Co(II)salen complex.

    Science.gov (United States)

    Vinck, Evi; Murphy, Damien M; Fallis, Ian A; Strevens, Robert R; Van Doorslaer, Sabine

    2010-03-01

    The activation of N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamino Co(II), [Co(II)(1)], by the addition of acetic acid under aerobic conditions has been investigated by a range of spectroscopic techniques including continuous-wave EPR, HYSCORE, pulsed ENDOR, and resonance Raman. These measurements have revealed for the first time the formation of a coordinated cobalt(III)-bound phenoxyl radical labeled [Co(III)(1(*))(OAc)(n)](OAc)(m) (n = m = 1 or n = 2, m = 0). This cobalt(III)-bound phenoxyl radical is characterized by the following spin Hamiltonian parameters: g(x) = 2.0060, g(y) = 2.0031, g(z) = 1.9943, A(x) = 17 MHz, A(y) = 55 MHz, and A(z) = 14 MHz. Although the radical contains coordinated acetate(s), the experiments unambiguously proved that the phenoxyl radical is situated on ligand (1) as opposed to a phenoxyl radical ligated to cobalt in the axial position. Density functional theory computations on different models corroborate the stability of such a phenoxyl radical species and suggest the ligation of one or two acetate molecules to the complex. A mechanism is proposed, which accounts for the formation of this unusual and extremely robust phenoxyl radical, never previously observed for [Co(1)].

  4. Plasma Lipidome Analysis by Liquid Chromatography-High Resolution Mass Spectrometry and Ion Mobility of Hypertriglyceridemic Patients on Extended-Release Nicotinic Acid: a Pilot Study.

    Science.gov (United States)

    Ferchaud-Roucher, Véronique; Croyal, Mikaël; Moyon, Thomas; Zair, Yassine; Krempf, Michel; Ouguerram, Khadija

    2017-06-01

    Plasma high triacylglycerols and low HDL-C concentration are associated with increased cardiovascular events. Extended-release nicotinic acid (ERN) was shown to reduce plasma triacylglycerols and total cholesterol but also to markedly increase high-density lipoprotein-cholesterol (HDL-C). No data on the effect of ERN on different species of triacylglycerol, cholesteryl ester, and phospholipids are available. In this study, we applied a nontargeted lipidomic approach to investigate the plasma and lipoproteins lipids profile of hypertriglyceridemic patients treated with ERN or a placebo in order to identify new lipids markers associated with this treatment. Eight hypertriglyceridemic patients enrolled in a crossover randomized trial with ERN for 8 weeks and treated with 2 g/day of ERN or a placebo. Ultra-performance liquid chromatography (UPLC) coupled to high-resolution mass spectrometry (HRMS) was used in mass spectrometry energy mode (HRMS E ) combined with ion mobility spectrometry to characterize the plasma and very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) lipidome. The accuracy and precision of the method were validated on plasma samples. Compared to placebo, among 155 plasma lipids characterized using UPLC-ESI-HRMS, a multivariate analysis revealed a significant increase of lysophosphatidylcholine (LPC 20:5), a significant decrease of phosphatidylethanolamine (PE 16:0/22:3) and sphingomyelin (SM d18:1/22:0) and a decrease of triacylglycerol (TG 16:0/16:1/18:2) after ERN treatment. Analysis of these lipids in lipoproteins showed an increase of LPC (20:5) in HDL, a decrease of PE (16:0/22:3) in HDL and LDL, of SM (d18:1/22:0) in VLDL and LDL and of TG (16:0/16:1/18:2) in VLDL. This lipidomic strategy characterized new specific lipid markers likely to be involved in the effect of ERN on cardiovascular risk opening a new strategy to analyze randomized controlled with this treatment. NCT01216956.

  5. Associations between Forkhead Box O1 (FoxO1 Expression and Indicators of Hepatic Glucose Production in Transition Dairy Cows Supplemented with Dietary Nicotinic Acid.

    Directory of Open Access Journals (Sweden)

    Asako Kinoshita

    Full Text Available Forkhead box protein O1 (FoxO1 is a transcription factor which promotes hepatic glucose production (HGP by up-regulating the transcription of gluconeogenic enzymes in monogastric species. The activity of FoxO1 is inhibited by insulin-induced phosphorylation. The aims of the present study were to find associations between FoxO1 expression and variables associated with HGP as affected by feeding regimen in dairy cows during the transition period. Twenty one healthy German Holstein cows were allocated to four groups (LC-CON, HC-CON, LC-NA with 5 cows/group and HC-NA with 6 cows/group, respectively. Cows received 0 (LC-CON and HC-CON or 24 (LC-NA and HC-NA g/d nicotinic acid with high (HC or low (LC concentrate proportion from -42 days (-41.8 + 4.8; mean + standard deviation relative to expected calving date (d-42 to d24. Liver biopsy was taken at d-42, 1, 21, and 100. The total protein expression of FoxO1 (tFoxO1 and the extent of phosphorylation of FoxO1 at serine 256 (pFoxO1 were analysed semiquantitatively by Western Blotting. The expression of hepatic mRNA of FoxO1 and seven genes associated with HGP was measured by real-time RT-PCR. Mixed model and Pearson's correlation were used for statistical evaluation with the level of significance at P<0.05. No dietary effect was observed either on feed intake, energy balance, or on the concentration of blood metabolites. Neither time nor diet affected the expression of FoxO1 total protein and mRNA. A NA × concentrate interaction was found in pFoxO1. However, no corresponding dietary effect was found in the mRNA expression of investigated genes. Different patterns of correlations between FoxO1-related variables and investigated indicators for HGP were found at d21 and 100. The results indicated that the regulation of HGP did not take place on the levels of mRNA and protein expression and the phosphorylation of FoxO1 in dairy cows in early lactation.

  6. Nicotine Vapor Inhalation Escalates Nicotine Self-Administration

    Science.gov (United States)

    Gilpin, Nicholas W.; Whitaker, Annie M.; Baynes, Brittni; Abdel, Abdelrahim Y.; Weil, Madelyn T.; George, Olivier

    2015-01-01

    Humans escalate their cigarette smoking over time, and a major obstacle in the field of pre-clinical nicotine addiction research has been the inability to produce escalated nicotine self-administration in rats. In Experiment 1, male Wistar rats were trained to respond for nicotine in 2-hr operant sessions, then exposed to chronic intermittent (12 hrs/day) nicotine vapor and repeatedly tested for nicotine self-administration at 8-12 hrs withdrawal. Rats were tested intermittently on days 1, 3 and 5 of the vapor exposure procedure, then tested on consecutive days 6-15 of nicotine vapor exposure. Rats exhibited transient increases in operant nicotine responding during intermittent testing, regardless of vapor condition, and this responding returned to baseline levels upon resumption of consecutive-days testing (i.e., nicotine deprivation effect). Nicotine vapor-exposed rats then escalated nicotine self-administration relative to both their own baseline (~200% increase) and non-dependent controls (~3x higher). In Experiment 2, rats were exposed or not exposed to chronic intermittent nicotine vapor, then tested for spontaneous and precipitated somatic signs of nicotine withdrawal. Eight hrs following removal from nicotine vapor, rats exhibited robust mecamylamine- precipitated somatic signs of withdrawal. There was a strong correlation between nicotine flow rate and air-nicotine concentration, and the air-nicotine concentrations used in Experiments 1 & 2 resemble concentrations experienced by human smokers. Collectively, these results suggest that chronic intermittent nicotine vapor inhalation produces somatic and motivational signs of nicotine dependence, the latter of which is evidenced by escalation of nicotine self-administration. PMID:23240929

  7. Nicotine vapor inhalation escalates nicotine self-administration.

    Science.gov (United States)

    Gilpin, Nicholas W; Whitaker, Annie M; Baynes, Brittni; Abdel, Abdelrahim Y; Weil, Madelyn T; George, Olivier

    2014-07-01

    Humans escalate their cigarette smoking over time, and a major obstacle in the field of pre-clinical nicotine addiction research has been the inability to produce escalated nicotine self-administration in rats. In experiment 1, male Wistar rats were trained to respond for nicotine in 2-hour operant sessions, then exposed to chronic intermittent (12 hours/day) nicotine vapor and repeatedly tested for nicotine self-administration at 8-12 hours of withdrawal. Rats were tested intermittently on days 1, 3 and 5 of the vapor exposure procedure, then tested with nicotine vapor exposure on 6-15 consecutive days. Rats exhibited transient increases in operant nicotine responding during intermittent testing, regardless of vapor condition, and this responding returned to baseline levels upon resumption of consecutive-days testing (i.e. nicotine deprivation effect). Nicotine vapor-exposed rats then escalated nicotine self-administration relative to both their own baseline (∼200% increase) and non-dependent controls (∼3× higher). In experiment 2, rats were exposed or not exposed to chronic intermittent nicotine vapor, then tested for spontaneous and precipitated somatic signs of nicotine withdrawal. Eight hours following removal from nicotine vapor, rats exhibited robust mecamylamine-precipitated somatic signs of withdrawal. There was a strong correlation between nicotine flow rate and air-nicotine concentration, and the air-nicotine concentrations used in experiments 1 and 2 resemble concentrations experienced by human smokers. Collectively, these results suggest that chronic intermittent nicotine vapor inhalation produces somatic and motivational signs of nicotine dependence, the latter of which is evidenced by escalation of nicotine self-administration. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  8. Dry matter and nutritional losses during aerobic deterioration of corn and sorghum silages as influenced by different lactic acid bacteria inocula.

    Science.gov (United States)

    Tabacco, E; Righi, F; Quarantelli, A; Borreani, G

    2011-03-01

    The economic damage that results from aerobic deterioration of silage is a significant problem for farm profitability and feed quality. This paper quantifies the dry matter (DM) and nutritional losses that occur during the exposure of corn and sorghum silages to air over 14 d and assesses the possibility of enhancing the aerobic stability of silages through inoculation with lactic acid bacteria (LAB). The trial was carried out in Northern Italy on corn (50% milk line) and grain sorghum (early dough stage) silages. The crops were ensiled in 30-L jars, without a LAB inoculant (C), with a Lactobacillus plantarum inoculum (LP), and with a Lactobacillus buchneri inoculum (LB; theoretical rate of 1 × 10(6) cfu/g of fresh forage). The pre-ensiled material, the silage at silo opening, and the aerobically exposed silage were analyzed for DM content, fermentative profiles, yeast and mold count, starch, crude protein, ash, fiber components, 24-h and 48-h DM digestibility and neutral detergent fiber (NDF) degradability. The yield and nutrient analysis data of the corn and sorghum silages were used as input for Milk2006 to estimate the total digestible nutrients, net energy of lactation, and milk production per Mg of DM. The DM fermentation and respiration losses were also calculated. The inocula influenced the in vitro NDF digestibility at 24h, the net energy for lactation (NE(L)), and the predicted milk yield per megagram of DM, whereas the length of time of air exposure influenced DM digestibility at 24 and 48 h, the NE(L), and the predicted milk yield per megagram of DM in the corn silages. The inocula only influenced the milk yield per megagram of DM and the air exposure affected the DM digestibility at 24h, the NE(L), and the milk yield per megagram of DM in the sorghum silages. The milk yield, after 14 d of air exposure, decreased to 1,442, 1,418, and 1,277 kg/Mg of DM for C, LB, and LP corn silages, respectively, compared with an average value of 1,568 kg of silage at

  9. Nicotine addiction and treatment.

    Science.gov (United States)

    Rose, J E

    1996-01-01

    The persistence of cigarette smoking despite widespread awareness of adverse health effects results from an underlying addiction to nicotine. Unaided attempts to quit smoking are generally unsuccessful. This article discusses nicotine addition and therapeutic techniques that have been or are being developed to relieve smoking withdrawal symptoms and promote abstinence from smoking. These techniques include nicotine chewing gum, skin patches, nasal sprays, and inhalers, as well as pharmacotherapies such as mecamylamine and clonidine, serotonergic treatments such as buspirone, and antidepressants such as buproprion. A nondrug approach using cigarette substitutes that mimic the airway sensations produced by cigarette smoke is also discussed.

  10. Thermodynamic studies of nicotinic acid

    OpenAIRE

    Gonçalves, Elsa Marisa Duarte Rodrigues, 1978-

    2011-01-01

    Tese de doutoramento, Química (Química Física), Universidade de Lisboa, Faculdade de Ciências, 2011 The work presented in this thesis was carried out at the Molecular Energetics group from “Centro de Química e Bioquímica” of “Faculdade de Ciências da Universidade de Lisboa”. The general research goal of the group is the study of the relationship between the energetics of molecules or groups of molecules and their structure and reactivity. In the recent years, the laboratory where I work...

  11. Nicotine inhibits memory CTL programming.

    Directory of Open Access Journals (Sweden)

    Zhifeng Sun

    Full Text Available Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development.

  12. Reward, addiction, withdrawal to nicotine.

    Science.gov (United States)

    De Biasi, Mariella; Dani, John A

    2011-01-01

    Nicotine is the principal addictive component that drives continued tobacco use despite users' knowledge of the harmful consequences. The initiation of addiction involves the mesocorticolimbic dopamine system, which contributes to the processing of rewarding sensory stimuli during the overall shaping of successful behaviors. Acting mainly through nicotinic receptors containing the α4 and β2 subunits, often in combination with the α6 subunit, nicotine increases the firing rate and the phasic bursts by midbrain dopamine neurons. Neuroadaptations arise during chronic exposure to nicotine, producing an altered brain condition that requires the continued presence of nicotine to be maintained. When nicotine is removed, a withdrawal syndrome develops. The expression of somatic withdrawal symptoms depends mainly on the α5, α2, and β4 (and likely α3) nicotinic subunits involving the epithalamic habenular complex and its targets. Thus, nicotine taps into diverse neural systems and an array of nicotinic acetylcholine receptor (nAChR) subtypes to influence reward, addiction, and withdrawal.

  13. 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.

  14. 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.

  15. The mitochondria-targeted imidazole substituted oleic acid 'TPP-IOA' affects mitochondrial bioenergetics and its protective efficacy in cells is influenced by cellular dependence on aerobic metabolism.

    Science.gov (United States)

    Maddalena, Lucas A; Ghelfi, Mikel; Atkinson, Jeffrey; Stuart, Jeffrey A

    2017-01-01

    A variety of mitochondria-targeted small molecules have been invented to manipulate mitochondrial redox activities and improve function in certain disease states. 3-Hydroxypropyl-triphenylphosphonium-conjugated imidazole-substituted oleic acid (TPP-IOA) was developed as a specific inhibitor of cytochrome c peroxidase activity that inhibits apoptosis by preventing cardiolipin oxidation and cytochrome c release to the cytosol. Here we evaluate the effects of TPP-IOA on oxidative phosphorylation in isolated mitochondria and on mitochondrial function in live cells. We demonstrate that, at concentrations similar to those required to achieve inhibition of cytochrome c peroxidase activity, TPP-IOA perturbs oxidative phosphorylation in isolated mitochondria. In live SH-SY5Y cells, TPP-IOA partially collapsed mitochondrial membrane potential, caused extensive fragmentation of the mitochondrial network, and decreased apparent mitochondrial abundance within 3h of exposure. Many cultured cell lines rely primarily on aerobic glycolysis, potentially making them less sensitive to small molecules disrupting oxidative phosphorylation. We therefore determined the anti-apoptotic efficacy of TPP-IOA in SH-SY5Y cells growing in glucose or in galactose, the latter of which increases reliance on oxidative phosphorylation for ATP supply. The anti-apoptotic activity of TPP-IOA that was observed in glucose media was not seen in galactose media. It therefore appears that, at concentrations required to inhibit cytochrome c peroxidase activity, TPP-IOA perturbs oxidative phosphorylation. In light of these data it is predicted that potential future therapeutic applications of TPP-IOA will be restricted to highly glycolytic cell types with limited reliance on oxidative phosphorylation. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-06-01

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

  17. Hydrothermal assembly, structures, topologies, luminescence, and magnetism of a novel series of coordination polymers driven by a trifunctional nicotinic acid building block.

    Science.gov (United States)

    Gu, Jin-Zhong; Liang, Xiao-Xiao; Cai, Yan; Wu, Jiang; Shi, Zi-Fa; Kirillov, Alexander M

    2017-08-22

    In this work, a trifunctional N,O-building block, 5-(4-carboxyphenoxy)nicotinic acid (H 2 cpna), that combines three distinct types of functional groups (COOH, N-pyridyl, and O-ether) was used for the hydrothermal assembly of thirteen new coordination compounds: [Co(μ 3 -Hcpna) 2 ] n (1), [Mn(μ 4 -cpna)(H 2 O)] n (2), [Mn(μ 4 -cpna)(H 2 O) 2 ] n (3), [Mn(μ-cpna)(2,2'-bipy)(H 2 O) 2 ] n (4), {[Ni(μ 3 -cpna)(2,2'-bipy)(H 2 O)] 2 ·H 2 O} n (5), {[Cd(μ 3 -cpna)(2,2'-bipy)]·2H 2 O} n (6), [Zn 2 (μ-cpna) 2 (2,2'-bipy) 2 ] (7), [Cu(μ-cpna)(2,2'-bipy)(H 2 O)] n (8), {[Mn(μ-cpna)(phen) 2 ]·6H 2 O} n (9), {[Ni(μ 3 -cpna)(phen)(H 2 O)]·H 2 O} n (10), [Zn 2 (μ-cpna) 2 (phen) 2 ] (11), {[Pb(μ 3 -cpna)(phen)]·H 2 O} n (12), and [Ni(μ 3 -cpna)(4,4'-bipy) 0.5 (H 2 O)] n (13). These products were synthesized from the corresponding metal(ii) chlorides, H 2 cpna, NaOH, and optional N-donor supporting ligands or templates {bis(4-pyridyl)amine (bpa), 2,2'-bipyridine (2,2'-bipy), 4,4'-bipyridine (4,4'-bipy), or 1,10-phenanthroline (phen)}. Products 1-13 were characterized in the solid state by standard methods, including elemental and thermogravimetric analysis (TGA), IR spectroscopy, and powder (PXRD) and single-crystal X-ray diffraction. The structures of 1-13 feature distinct structural types, namely the 3D metal-organic frameworks (MOFs 1-3), the 2D coordination polymers (5, 6, 10, 12, and 13), the 1D coordination polymers (4, 8, and 9), and the 0D discrete cyclic dimers (7 and 11). Such a wide structural diversity of 1-13 is driven by various factors, including the type of the metal(ii) node, the deprotonation degree of H 2 cpna, and/or the type of supporting ligand or template. Notably, an addition of bpa can tune the structure of MOF 3 by the template effect. Topological classification of underlying metal-organic networks was performed, leading to several distinct topological nets: rtl (in 1), hxg-d-4-C2/m (in 2), sra (in 3), 2C1 (in 4, 8 and 9), fes (in 5, 10

  18. 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.

  19. 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...

  20. Neurocognitive Insights in Nicotine Addiction

    NARCIS (Netherlands)

    M. Luijten (Maartje)

    2012-01-01

    textabstractIn the Netherlands, 27% of the population is currently smoking. Nicotine is among the most addictive substances of abuse. Thirty-two percent of the people who tried smoking develop nicotine dependence within ten year. This percentage is higher for nicotine than for other substances of

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

    Science.gov (United States)

    D'Souza, Manoranjan S

    2016-01-01

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

  2. Nicotine Vapor Inhalation Escalates Nicotine Self-Administration

    OpenAIRE

    Gilpin, Nicholas W.; Whitaker, Annie M.; Baynes, Brittni; Abdel, Abdelrahim Y.; Weil, Madelyn T.; George, Olivier

    2012-01-01

    Humans escalate their cigarette smoking over time, and a major obstacle in the field of pre-clinical nicotine addiction research has been the inability to produce escalated nicotine self-administration in rats. In Experiment 1, male Wistar rats were trained to respond for nicotine in 2-hr operant sessions, then exposed to chronic intermittent (12 hrs/day) nicotine vapor and repeatedly tested for nicotine self-administration at 8-12 hrs withdrawal. Rats were tested intermittently on days 1, 3 ...

  3. Stability of nicotinate and dodecyl sulfate in a Lewis acidic ionic liquid for aluminum electroplating and characterization of their degradation products.

    Science.gov (United States)

    Kosmus, Patrick; Steiner, Oliver; Goessler, Walter; Gollas, Bernhard; Fauler, Gisela

    2016-04-01

    Plating bath additives are essential for optimization of the morphology of electroplated layers. The ionic liquid 1-ethyl-3-methylimidazolium (EMIM) chloride plus 1.5 mol equivalents of AlCl3 has great potential for electroplating of aluminum. In this study, the chemical and electrochemical stability of the additives EMIM-nicotinate and sodium dodecyl sulfate and their effect on the stability of EMIM was investigated and analyzed. Nicotinate and its electrochemical decomposition product β-picoline could be detected and we show with a single HPLC-UV-MS method that EMIM is not affected by the decomposition of this additive. An adapted standard HPLC-UV-MS method together with GC-MS and ion chromatography was used to analyze the decomposition products of SDS and possible realkylation products of EMIM. Several volatile medium and short chain-length alkanes as well as sulfate ions have been found as decomposition products of SDS. Alkenium ions formed as intermediates during the decomposition of SDS realkylate EMIM to produce mono- up to pentasubstituted alkyl-imidazoles. A reaction pathway involving Wagner-Meerwein rearrangements and Friedel-Crafts alkylations has been suggested to account for the formation of the detected products. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Full-gestational exposure to nicotine and ethanol augments nicotine self-administration by altering ventral tegmental dopaminergic function due to NMDA receptors in adolescent rats.

    Science.gov (United States)

    Roguski, Emily E; Sharp, Burt M; Chen, Hao; Matta, Shannon G

    2014-03-01

    In adult rats, we have shown full-gestational exposure to nicotine and ethanol (Nic + EtOH) augmented nicotine self-administration (SA) (increased nicotine intake) compared to pair-fed (PF) offspring. Therefore, we hypothesized that full-gestational exposure to Nic + EtOH disrupts control of dopaminergic (DA) circuitry by ventral tegmental area (VTA) NMDA receptors, augmenting nicotine SA and DA release in nucleus accumbens (NAcc) of adolescents. Both NAcc DA and VTA glutamate release were hyper-responsive to intra-VTA NMDA in Nic + EtOH offspring versus PF (p = 0.03 and 0.02, respectively). Similarly, DA release was more responsive to i.v. nicotine in Nic + EtOH offspring (p = 0.02). Local DL-2-Amino-5-phosphonopentanoic acid sodium salt (AP5) (NMDA receptor antagonist) infusion into the VTA inhibited nicotine-stimulated DA release in Nic + EtOH and PF offspring. Nicotine SA was augmented in adolescent Nic + EtOH versus PF offspring (p = 0.000001). Daily VTA microinjections of AP5 reduced nicotine SA by Nic + EtOH offspring, without affecting PF (p = 0.000032). Indeed, nicotine SA in Nic + EtOH offspring receiving AP5 was not different from PF offspring. Both VTA mRNA transcripts and NMDA receptor subunit proteins were not altered in Nic + EtOH offspring. In summary, adolescent offspring exposed to gestational Nic + EtOH show markedly increased vulnerability to become dependent on nicotine. This reflects the enhanced function of a subpopulation of VTA NMDA receptors that confer greater nicotine-induced DA release in NAcc. We hypothesized that concurrent gestational exposure to nicotine and ethanol would disrupt the control of VTA dopaminergic circuitry by NMDA receptors. Resulting in the augmented nicotine self-administration (SA) in adolescent offspring. © 2013 International Society for Neurochemistry.

  5. Cellular Events in Nicotine Addiction

    OpenAIRE

    Penton, Rachel E.; Lester, Robin A.J.

    2009-01-01

    In the twenty-five years since the observation that chronic exposure to nicotine could regulate the number and function of high affinity nicotine binding sites in the brain there has been a major effort to link alterations in nicotinic acetylcholine receptors (nAChRs) to nicotine-induced behaviors that drive the addiction to tobacco products. Here we review the proposed roles of various nAChR subtypes in the addiction process, with emphasis on how they are regulated by nicotine and the implic...

  6. Neuromodulation of Aerobic Exercise—A Review

    Directory of Open Access Journals (Sweden)

    Saskia eHeijnen

    2016-01-01

    Full Text Available Running, and aerobic exercise in general, is a physical activity that increasingly many people engage in but that also has become popular as a topic for scientific research. Here we review the available studies investigating whether and to which degree aerobic exercise modulates hormones, amino acids, and neurotransmitters levels. In general, it seems that factors such as genes, gender, training status, and hormonal status need to be taken into account to gain a better understanding of the neuromodular underpinnings of aerobic exercise. More research using longitudinal studies and considering individual differences is necessary to determine actual benefits. We suggest that, in order to succeed, aerobic exercise programs should include optimal periodization, prevent overtraining and be tailored to interindividual differences, including neuro-developmental and genetically-based factors.

  7. BEHAVIORAL MECHANISMS UNDERLYING NICOTINE REINFORCEMENT

    Science.gov (United States)

    Rupprecht, Laura E.; Smith, Tracy T.; Schassburger, Rachel L.; Buffalari, Deanne M.; Sved, Alan F.; Donny, Eric C.

    2015-01-01

    Cigarette smoking is the leading cause of preventable deaths worldwide and nicotine, the primary psychoactive constituent in tobacco, drives sustained use. The behavioral actions of nicotine are complex and extend well beyond the actions of the drug as a primary reinforcer. Stimuli that are consistently paired with nicotine can, through associative learning, take on reinforcing properties as conditioned stimuli. These conditioned stimuli can then impact the rate and probability of behavior and even function as conditioning reinforcers that maintain behavior in the absence of nicotine. Nicotine can also act as a conditioned stimulus, predicting the delivery of other reinforcers, which may allow nicotine to acquire value as a conditioned reinforcer. These associative effects, establishing non-nicotine stimuli as conditioned stimuli with discriminative stimulus and conditioned reinforcing properties as well as establishing nicotine as a conditioned stimulus, are predicted by basic conditioning principles. However, nicotine can also act non-associatively. Nicotine directly enhances the reinforcing efficacy of other reinforcing stimuli in the environment, an effect that does not require a temporal or predictive relationship between nicotine and either the stimulus or the behavior. Hence, the reinforcing actions of nicotine stem both from the primary reinforcing actions of the drug (and the subsequent associative learning effects) as well as the reinforcement enhancement action of nicotine which is non-associative in nature. Gaining a better understanding of how nicotine impacts behavior will allow for maximally effective tobacco control efforts aimed at reducing the harm associated with tobacco use by reducing and/or treating its addictiveness. PMID:25638333

  8. Nicotine Vapor Method to Induce Nicotine Dependence in Rodents.

    Science.gov (United States)

    Kallupi, Marsida; George, Olivier

    2017-07-05

    Nicotine, the main addictive component of tobacco, induces potentiation of brain stimulation reward, increases locomotor activity, and induces conditioned place preference. Nicotine cessation produces a withdrawal syndrome that can be relieved by nicotine replacement therapy. In the last decade, the market for electronic cigarettes has flourished, especially among adolescents. The nicotine vaporizer or electronic nicotine delivery system is a battery-operated device that allows the user to simulate the experience of tobacco smoking without inhaling smoke. The device is designed to be an alternative to conventional cigarettes that emits vaporized nicotine inhaled by the user. This report describes a procedure to vaporize nicotine in the air to produce blood nicotine levels in rodents that are clinically relevant to those that are observed in humans and produce dependence. We also describe how to construct the apparatus to deliver nicotine vapor in a stable, reliable, and consistent manner, as well as how to analyze air for nicotine content. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  9. 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.

  10. 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.

  11. Chronic nicotine pretreatment is sufficient to upregulate α4* nicotinic receptors and increase oral nicotine self-administration in mice

    OpenAIRE

    Renda, Anthony; Nashmi, Raad

    2014-01-01

    Background Understanding the underlying causes of nicotine addiction will require a multidisciplinary approach examining the key molecular, cellular and neuronal circuit functional changes that drive escalating levels of nicotine self-administration. In this study, we examined whether mice pretreated with chronic nicotine, at a dosing regimen that results in maximal nicotinic acetylcholine receptor (nAChR) upregulation, would display evidence of nicotine-dependent behaviour during nicotine se...

  12. Effects of Aerobic Exercise Training on Psychosocial Status and ...

    African Journals Online (AJOL)

    an 8 weeks continuous training (60%‑79% HR max) of between 45 and 60 min, 3 times per week, while the controls group ... Lamina and Okoye: Effects of aerobic exercise training on psychosocial status and serum uric acid in men such as high energy/drive, ..... 20. Crews DJ, Landers DM. A meta‑analytic review of aerobic.

  13. α7 Nicotinic Agonist AR-R17779 Protects Mice against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in a Spleen-Dependent Way

    Directory of Open Access Journals (Sweden)

    Andrea Grandi

    2017-11-01

    Full Text Available The existence of a cholinergic anti-inflammatory pathway negatively modulating the inflammatory and immune responses in various clinical conditions and experimental models has long been postulated. In particular, the protective involvement of the vagus nerve and of nicotinic Ach receptors (nAChRs has been proposed in intestinal inflammation and repeatedly investigated in DSS- and TNBS-induced colitis. However, the role of α7 nAChRs stimulation is still controversial and the potential contribution of α4β2 nAChRs has never been explored in this experimental condition. Our aims were therefore to pharmacologically investigate the role played by both α7 and α4β2 nAChRs in the modulation of the local and systemic inflammatory responses activated in TNBS-induced colitis in mice and to assess the involvement of the spleen in nicotinic responses. To this end, TNBS-exposed mice were sub-acutely treated with various subcutaneous doses of highly selective agonists (AR-R17779 and TC-2403 and antagonists (methyllycaconitine and dihydro-β-erythroidine of α7 and α4β2 nAChRs, respectively, or with sulfasalazine 50 mg/kg per os and clinical and inflammatory responses were evaluated by means of biochemical, histological and flow cytometry assays. α4β2 ligands evoked weak and contradictory effects, while α7 nAChR agonist AR-R17779 emerged as the most beneficial treatment, able to attenuate several local markers of colitis severity and to revert the rise in splenic T-cells and in colonic inflammatory cytokines levels induced by haptenization. After splenectomy, AR-R17779 lost its protective effects, demonstrating for the first time that, in TNBS-model of experimental colitis, the anti-inflammatory effect of exogenous α7 nAChR stimulation is strictly spleen-dependent. Our findings showed that the selective α7 nAChRs agonist AR-R17779 exerted beneficial effects in a model of intestinal inflammation characterized by activation of the adaptive immune

  14. Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig.

    Science.gov (United States)

    Donnerer, Josef; Liebmann, Ingrid

    2015-01-01

    In the present study, the direct drug effects of nicotine and its effects on the cholinergic twitch responses of the electrically stimulated longitudinal muscle-myenteric plexus strip from the ileum of guinea pig were investigated. Nicotine dose-dependently (0.3-10 µmol/l) evoked the well-known contractile responses on its own. Whereas the interposed twitch responses remained present without a change in height at 1 µmol/l nicotine, a nicotine concentration of 3 µmol/l slightly and a concentration of 10 µmol/l markedly diminished the twitch during their presence. After the washout of 1-10 µmol/l nicotine, the height of the twitch response was also temporarily and significantly reduced by 30-77%. The P2X purinoceptor agonist αβ-methylene ATP (1-10 µmol/l) dose-dependently induced contractions on its own and reduced the twitch response during its presence in the organ bath; however, it did not diminish the twitch responses after washout of the drug as nicotine did. The P2X antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid, the NMDA channel blocker MK-801 and the inhibitor of small conductance Ca(2+)-activated K(+) (SK) channels apamin reduced the contractile effect of 1 µmol/l nicotine. Apamin also significantly prevented the 'post-nicotine inhibition of the twitch' following the washout of 1-3 µmol/l nicotine. As a conclusion, we provide evidence for a functional interaction between nicotinic receptors and the P2X receptors in the ileum of the guinea pig. The 'post-nicotine inhibition of the twitch' is not due to nicotinic acetylcholine receptor desensitization or transmitter depletion, but most probably the secondary effects of nicotine on SK channels determine the reduced cholinergic motor neuron excitability. © 2015 S. Karger AG, Basel.

  15. Nicotine and periodontal tissues

    Directory of Open Access Journals (Sweden)

    Malhotra Ranjan

    2010-01-01

    Full Text Available Tobacco use has been recognized to be a significant risk factor for the development and progression of periodontal disease. Its use is associated with increased pocket depths, loss of periodontal attachment, alveolar bone and a higher rate of tooth loss. Nicotine, a major component and most pharmacologically active agent in tobacco is likely to be a significant contributing factor for the exacerbation of periodontal diseases. Available literature suggests that nicotine affects gingival blood flow, cytokine production, neutrophil and other immune cell function; connective tissue turnover, which can be the possible mechanisms responsible for overall effects of tobacco on periodontal tissues. Inclusion of tobacco cessation as a part of periodontal therapy encourages dental professionals to become more active in tobacco cessation counseling. This will have far reaching positive effects on our patients′ oral and general health.

  16. Cd (II) and holodirected lead (II) 3D-supramolecular coordination polymers based on nicotinic acid: Structure, fluorescence property and photocatalytic activity

    Science.gov (United States)

    Etaiw, Safaa El-din H.; Abd El-Aziz, Dina M.; Marie, Hassan; Ali, Elham

    2018-05-01

    Two new supramolecular coordination polymers namely {[Cd(NA)2(H2O)]}, SCP 1 and {[Pb(NA)2]}, SCP 2, (NA = nicotinate ligand) were synthesized by self-assembly method and structurally characterized by different analytical and spectroscopic methods. Single-crystal X-ray diffraction showed that SCP 1 extend in three dimensions containing bore structure where the 3D- network is constructed via interweaving zigzag chains. The Cd atom coordinates to (O4N2) atoms forming distorted-octahedral configuration. The structure of SCP 2 extend down the projection of the b-axis creating parallel zigzag 1D-chains connected by μ2-O2 atoms and H-bonds forming a holodirected lead (II) hexagonal bi-pyramid configuration. SCP 2 extend to 3D-network via coordinate and hydrogen bonds. The thermal stability, photoluminescence properties, photocatalytic activity for the degradation of methylene blue dye (MB) under UV-irradiation and sunlight irradiation were also studied.

  17. Extraction of structural extracellular polymeric substances from aerobic granular sludge

    NARCIS (Netherlands)

    Felz, S.; Al-zuhairy, S.H.K.; Aarstad, Olav Andreas; van Loosdrecht, Mark C.M.; Lin, Y.

    2016-01-01

    To evaluate and develop methodologies for the extraction of gel-forming extracellular polymeric substances (EPS), EPS from aerobic granular sludge (AGS) was extracted using six different methods (centrifugation, sonication, ethylenediaminetetraacetic acid (EDTA), formamide with sodium hydroxide

  18. The psychobiology of nicotine dependence

    Directory of Open Access Journals (Sweden)

    D. J. K. Balfour

    2008-12-01

    Full Text Available There is abundant evidence to show that nicotine is the principal addictive component of tobacco smoke. The results of laboratory studies have shown that nicotine has many of the behavioural and neurobiological properties of a drug of dependence. This article focuses on the evidence that nicotine has the rewarding and reinforcing properties typical of an addictive drug and that these properties are mediated, in part, by its effects on mesolimbic dopamine neurones. However, in many experimental models of dependence, nicotine has relatively weak reinforcing properties that do not appear to explain adequately the powerful addiction to tobacco smoke experienced by many habitual smokers. Some of the reasons for this conundrum will be covered herein. This article focuses on the hypothesis that sensory stimuli and other pharmacologically active components in tobacco smoke play a pivotal role in the addiction to nicotine when it is inhaled in tobacco smoke. The article will discuss the evidence that dependence upon tobacco smoke reflects a complex interaction between nicotine and the components of the smoke, which are mediated by complementary effects of nicotine on the dopamine projections to the shell and core subdivisions of the accumbens. It will also discuss the extent to which the complexity of the dependence explains why nicotine replacement therapy does not provide a completely satisfying aid to smoking cessation and speculate on the properties treatments should exhibit if they are to provide a better treatment for tobacco dependence than those currently available.

  19. Granular insular cortex inactivation as a novel therapeutic strategy for nicotine addiction.

    Science.gov (United States)

    Forget, Benoit; Pushparaj, Abhiram; Le Foll, Bernard

    2010-08-01

    Nicotine is the principal component of tobacco smoke, resulting in addiction, and recent evidence suggests that damage to the insular cortex (insula) disrupts tobacco addiction in human smokers. However, the effect of an inactivation of this structure in an animal model of nicotine addiction has yet to be evaluated. To study this question, we investigated the effects of reversible inactivation of the granular insula by local injection of a gamma-aminobutyric acid agonists mixture (baclofen/muscimol) on nicotine self-administration (SA) under fixed and progressive ratio and on reinstatement of nicotine seeking induced by nicotine priming or nicotine-associated cues in rats. We also evaluated the effects of granular insula inactivation on food SA and relapse as a control. The inactivation of the granular insula decreased nicotine SA under both fixed and progressive ratios without affecting the SA of food under the same schedules of reinforcement. This inactivation also prevented the reinstatement, after extinction, of nicotine seeking induced by nicotine-associated cues or nicotine priming without modifying the reinstatement of food seeking. Our study indicates that the integrity of the granular insula is necessary for exhibiting motivation to take nicotine and to relapse to nicotine seeking but not for consuming food pellets or to relapse for food seeking. Indeed, it might be interesting to study the effect of methods that are able to modulate the activity of the insula--such as repetitive transcranial magnetic stimulation or deep brain stimulation--on tobacco addiction and relapse in humans. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Resistance Versus Aerobic Exercise

    Science.gov (United States)

    Yardley, Jane E.; Kenny, Glen P.; Perkins, Bruce A.; Riddell, Michael C.; Balaa, Nadia; Malcolm, Janine; Boulay, Pierre; Khandwala, Farah; Sigal, Ronald J.

    2013-01-01

    OBJECTIVE In type 1 diabetes, small studies have found that resistance exercise (weight lifting) reduces HbA1c. In the current study, we examined the acute impacts of resistance exercise on glycemia during exercise and in the subsequent 24 h compared with aerobic exercise and no exercise. RESEARCH DESIGN AND METHODS Twelve physically active individuals with type 1 diabetes (HbA1c 7.1 ± 1.0%) performed 45 min of resistance exercise (three sets of seven exercises at eight repetitions maximum), 45 min of aerobic exercise (running at 60% of Vo2max), or no exercise on separate days. Plasma glucose was measured during and for 60 min after exercise. Interstitial glucose was measured by continuous glucose monitoring 24 h before, during, and 24 h after exercise. RESULTS Treatment-by-time interactions (P exercise. Plasma glucose decreased from 8.4 ± 2.7 to 6.8 ± 2.3 mmol/L (P = 0.008) during resistance exercise and from 9.2 ± 3.4 to 5.8 ± 2.0 mmol/L (P = 0.001) during aerobic exercise. No significant changes were seen during the no-exercise control session. During recovery, glucose levels did not change significantly after resistance exercise but increased by 2.2 ± 0.6 mmol/L (P = 0.023) after aerobic exercise. Mean interstitial glucose from 4.5 to 6.0 h postexercise was significantly lower after resistance exercise versus aerobic exercise. CONCLUSIONS Resistance exercise causes less initial decline in blood glucose during the activity but is associated with more prolonged reductions in postexercise glycemia than aerobic exercise. This might account for HbA1c reductions found in studies of resistance exercise but not aerobic exercise in type 1 diabetes. PMID:23172972

  1. 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.

  2. Selective aerobic oxidation of 5-(hydroxymethyl)furfural to 2,5-diformylfuran or 2-formyl-5-furancarboxylic acid in water using MgO·CeO2 mixed oxides as catalysts.

    Science.gov (United States)

    Dibenedetto, Angela; Ventura, Maria; Lobefaro, Francesco; de Giglio, Elvira; Distaso, Monica; Nocito, Francesco

    2018-03-07

    Mixed oxides based on MgO·CeO2 were used, as efficient catalysts, in the aerobic oxidation of 5-(hydroxymethyl)furfural (5-HMF) to afford, with very high selectivity, either 2,5-diformylfuran (DFF, 99%) or 2-formyl-5-furancarboxylic acid (FFCA, 90%) depending on the reaction conditions. 5-Hydroxymethyl-2-furancarboxylic acid (HMFCA, 57-90%) was formed only at low concentration of 5-HMF (catalysts gave important information about their acid-base properties, which drive the selectivity of the reaction towards DFF. FFCA was formed from DFF for longer reaction times. Catalysts were studied by XPS and XRD before and after catalytic runs to identify the reason why they undergo reversible deactivation. XRD has clearly shown that MgO is hydrated to Mg(OH)2 which, even if not leached out, changes the basic properties of the catalyst that becomes less active after some time. Calcination of the recovered catalyst allows recovering their initial activity. The catalyst is, thus, recoverable (>99%) and reusable. The use of mixed oxides allows tune the basicity of catalysts, avoiding external bases for efficient and selective conversion of 5-HMF and waste formation, resulting in an environmentally friendly, sustainable process. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats

    Science.gov (United States)

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

    2013-01-01

    Rationale Exercise appears to be a promising non-pharmacological treatment for nicotine addiction that may be useful for the vulnerable adolescent population. Objectives To determine if wheel running, an animal model of aerobic exercise, during an abstinence period would decrease subsequent nicotine-seeking in rats that had extended access to nicotine self-administration during adolescence. Methods Male adolescent rats (n = 55) were trained to self-administer saline or nicotine infusions (5 or 10 μg/kg) under a fixed ratio 1 schedule with a maximum of 20 infusions/day beginning on postnatal day 30. After 5 days, access was extended to 23-hr/day with unlimited infusions for a total of 10 days. After the last self-administration session, rats were moved to polycarbonate cages for a 10-day abstinence period where they either had access to a locked or unlocked running wheel for 2-hr/day. Nicotine-seeking was examined following the 10th day of abstinence under a within-session extinction/cue-induced reinstatement paradigm. Results Intake was higher at the 10 μg/kg dose as compared to the 5 μg/kg dose; however, intake did not differ within doses prior to wheel assignment. Compared to saline controls, rats that self-administered nicotine at either dose showed a significant increase in drug-seeking during extinction, and consistent with our hypothesis, exercise during abstinence attenuated this effect. Nicotine led to modest, but significant levels of cue-induced reinstatement; however, in this adolescent-onset model, levels were variable and not affected by exercise. Conclusions Exercise may effectively reduce relapse vulnerability for adolescent-onset nicotine addiction. PMID:23371488

  4. Nicotine Elicits Methamphetamine-Seeking in Rats Previously Administered Nicotine

    OpenAIRE

    Neugebauer, N. M.; Harrod, S. B.; Bardo, M. T.

    2009-01-01

    Research has indicated a high correlation between psychostimulant use and tobacco cigarette smoking in human substance abusers. The objective of the current study was to examine the effects of acute and repeated nicotine administration on responding for intravenous methamphetamine (0.03 mg/kg/infusion) in a rodent model of self-administration, as well as the potential of nicotine to induce reinstatement of previously extinguished drug-taking behavior in male Sprague-Dawley rats. In addition, ...

  5. Anaerobic and aerobic acetylene hydratase

    Indian Academy of Sciences (India)

    Administrator

    Acetaldehyde is the first metabolite produced during acetylene degradation by bacteria either aerobically or anaerobically. Conversion of acetylene into acetaldehyde, ethanol, acetate, and biomass occurs in anaerobic cultures of Palobacter acetylinicus or aerobically with Mycobacterium lacticola, Nocardia rhodochrous, ...

  6. Níveis de cromo-ácido nicotínico em dietas de suínos em crescimento e terminação Levels of chromium-nicotinic acid in diets for growing-finishing pigs

    Directory of Open Access Journals (Sweden)

    Gustavo Julio Mello Monteiro de Lima

    1999-03-01

    Full Text Available O objetivo deste estudo foi avaliar os efeitos de níveis crescentes de cromo dietético, na forma de ácido nicotínico, sobre o desempenho e nas características de carcaça de suínos. Noventa e seis suínos (Landrace x Large White x Duroc, machos castrados e fêmeas, com peso médio inicial de 25,93±0,57 kg foram distribuídos ao acaso em baias de dois animais do mesmo sexo, segundo um esquema fatorial 6 x 2 (6 níveis de Cr e 2 sexos. Uma dieta basal (0 ppb Cr foi suplementada com 100, 200, 300, 400 e 500 ppb de Cr, na forma de Cr-ácido nicotínico, incluído através do premix vitamínico. Os animais, aos 70 dias de experimento, foram pesados, abatidos, e as carcaças avaliadas utilizando-se a pistola Hennessy e o Método Brasileiro de Classificação de Carcaças. Houve efeito significativo (P0,05 do nível de Cr sobre qualquer dos parâmetros estudados, seja de desempenho ou de avaliação de carcaça por qualquer dos métodos utilizados. A adição de níveis de até 500 ppb de Cr, na forma de Cr-ácido nicotínico, não altera o desempenho e a qualidade de carcaça de suínos em crescimento e em terminação.Ninety-six barrows and gilts (Landrace x Large White x Duroc, with average initial weight of 25.93±0.57 kg, were used in order to evaluate the effects of Cr on performance and carcass characteristics, in a random block design, according to a 6 x 2 factorial arrangement (6 Cr levels x 2 sexes. A basal diet (0 ppb Cr was supplemented with 100, 200, 300, 400 e 500 ppb Cr, as Cr-nicotinic acid, added to the vitamin premix. On the 70th day of the experimental period, all animals were weighted, slaughtered and had their carcass evaluated using Hennessy probe and the Brazilian Carcass Classification Method. There was a significant sex effect (P0.05. The addition of up to 500 ppb Cr in the diet, in the form of Cr-nicotinic acid, did not improve performance and carcass traits of growing-finishing pigs.

  7. Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT) Activity by Small Molecule GMX1778 Regulates Reactive Oxygen Species (ROS)-mediated Cytotoxicity in a p53- and Nicotinic Acid Phosphoribosyltransferase1 (NAPRT1)-dependent Manner*

    Science.gov (United States)

    Cerna, David; Li, Hongyun; Flaherty, Siobhan; Takebe, Naoko; Coleman, C. Norman; Yoo, Stephen S.

    2012-01-01

    Cancer cells undergo mitosis more frequently than normal cells and thus have increased metabolic needs, which in turn lead to higher than normal reactive oxygen species (ROS) production. Higher ROS production increases cancer cell dependence on ROS scavenging systems to balance the increased ROS. Selectively modulating intracellular ROS in cancers by exploiting cancer dependence on ROS scavenging systems provides a useful therapeutic approach. Essential to developing these therapeutic strategies is to maintain physiologically low ROS levels in normal tissues while inducing ROS in cancer cells. GMX1778 is a specific inhibitor of nicotinamide phosphoribosyltransferase, a rate-limiting enzyme required for the regeneration of NAD+ from nicotinamide. We show that GMX1778 increases intracellular ROS in cancer cells by elevating the superoxide level while decreasing the intracellular NAD+ level. Notably, GMX1778 treatment does not induce ROS in normal cells. GMX1778-induced ROS can be diminished by adding nicotinic acid (NA) in a NA phosphoribosyltransferase 1 (NAPRT1)-dependent manner, but NAPRT1 is lost in a high frequency of glioblastomas, neuroblastomas, and sarcomas. In NAPRT1-deficient cancer cells, ROS induced by GMX1778 was not susceptible to treatment with NA. GMX1778-mediated ROS induction is p53-dependent, suggesting that the status of both p53 and NAPRT1 might affect tumor apoptosis, as determined by annexin-V staining. However, as determined by colony formation, GMX1778 long term cytotoxicity in cancer cells was only prevented by the addition of NA to NAPRT1-expressing cells. Exposure to GMX1778 may be a novel way of inducing ROS selectively in NAPRT1-negative tumors without inducing cytotoxic ROS in normal tissue. PMID:22570471

  8. Nicotine stimulates expression of proteins implicated in peripheral and central sensitization.

    Science.gov (United States)

    Hawkins, J L; Denson, J E; Miley, D R; Durham, P L

    2015-04-02

    Pain patients who are nicotine dependent report a significantly increased incidence and severity of pain intensity. The goal of this study was to determine the effects of prolonged nicotine administration on inflammatory proteins implicated in the development of peripheral and central sensitization of the trigeminal system. Behavioral, immunohistochemical, and microarray studies were utilized to investigate the effects of nicotine administered daily for 14 days via an Alzet® osmotic pump in Sprague Dawley rats. Systemic nicotine administration caused a significant increase in nocifensive withdrawals to mechanical stimulation of trigeminal neurons. Nicotine stimulated expression of the pro-inflammatory signal transduction proteins phosphorylated-extracellular signal-regulated kinase (p-ERK), phosphorylated-c-Jun N-terminal kinase (p-JNK), and protein kinase A (PKA) in the spinal trigeminal nucleus. Nicotine also promoted elevations in the expression of glial fibrillary acidic protein (GFAP), a biomarker of activated astrocytes, and the microglia biomarker ionized calcium-binding adapter molecule 1 (Iba1). Similarly, levels of eleven cytokines were significantly elevated with the largest increase in expression of TNF-α. Levels of PKA, p-ERK, and p-JNK in trigeminal ganglion neurons were increased by nicotine. Our findings demonstrate that prolonged systemic administration of nicotine promotes sustained behavioral and cellular changes in the expression of key proteins in the spinal trigeminal nucleus and trigeminal ganglion implicated in the development and maintenance of peripheral and central sensitization. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Nicotine-induced embryonic malformations mediated by apoptosis from increasing intracellular calcium and oxidative stress.

    Science.gov (United States)

    Zhao, Zhiyong; Reece, E Albert

    2005-10-01

    Tobacco smoking by women during pregnancy increases the risk of congenital birth defects in the infants. Among the smoke products, nicotine is believed to be the major teratogenic factor that perturbs embryonic development. However, the role of nicotine in embryonic malformations has not been addressed, and the mechanisms by which nicotine affects embryonic development remain to be delineated. To investigate the effects of nicotine on early embryogenesis, murine embryos at embryonic day (E) 8.5 were dissected out of the uteri, cultured in a roller bottle system, and treated with nicotine (0.6-6 microM) or vehicle. Embryonic morphogenesis and growth were examined in terms of structural morphology and crown/rump length, respectively. Programmed cell death (apoptosis) was assessed using LysoTracker Red staining of whole mount embryos and TUNEL assay of tissue sections. Changes in intracellular calcium concentration ([Ca2+]i) and reactive oxygen species (ROS) production were assessed using fluorescent dyes (Flu-4, AM; H2DCFDA, respectively) under a confocal microscope. To further investigate the role of intracellular calcium and ROS in nicotine-induced embryopathy, embryos were treated with BAPTA-AM (2 microM) to inhibit [Ca2+]i elevation and ascorbic acid (vitamin C; 100 microg/ml) to scavenge ROS in presence of nicotine (6 microM). The embryos treated with nicotine in 3-6 microM were smaller than those treated with vehicle. Most of the embryos had open neural tube in the anterior (brain) regions. The embryos treated with 6 microM nicotine also exhibited severe defects in the posterior trunk, resembling caudal dysplasia. Excessive apoptosis was observed in the deformed structures. Significant increases in [Ca2+]i and ROS were seen in the tissues that had higher levels of apoptosis. Furthermore, inhibition of [Ca2+]i and scavenging of ROS significantly reduced embryonic malformation and apoptotic rates in the embryos. Nicotine affects embryonic development in a

  10. The effects of a pre-workout supplement containing caffeine, creatine, and amino acids during three weeks of high-intensity exercise on aerobic and anaerobic performance.

    Science.gov (United States)

    Smith, Abbie E; Fukuda, David H; Kendall, Kristina L; Stout, Jeffrey R

    2010-02-15

    A randomized, single-blinded, placebo-controlled, parallel design study was used to examine the effects of a pre-workout supplement combined with three weeks of high-intensity interval training (HIIT) on aerobic and anaerobic running performance, training volume, and body composition. Twenty-four moderately-trained recreational athletes (mean +/- SD age = 21.1 +/- 1.9 yrs; stature = 172.2 +/- 8.7 cm; body mass = 66.2 +/- 11.8 kg, VO2max = 3.21 +/- 0.85 l.min-1, percent body fat = 19.0 +/- 7.1%) were assigned to either the active supplement (GT, n = 13) or placebo (PL, n = 11) group. The active supplement (Game Time(R), Corr-Jensen Laboratories Inc., Aurora, CO) was 18 g of powder, 40 kcals, and consisted of a proprietary blend including whey protein, cordyceps sinensis, creatine, citrulline, ginseng, and caffeine. The PL was also 18 g of powder, 40 kcals, and consisted of only maltodextrin, natural and artificial flavors and colors. Thirty minutes prior to all testing and training sessions, participants consumed their respective supplements mixed with 8-10 oz of water. Both groups participated in a three-week HIIT program three days per week, and testing was conducted before and after the training. Cardiovascular fitness (VO2max) was assessed using open circuit spirometry (Parvo-Medics TrueOne(R) 2400 Metabolic Measurement System, Sandy, UT) during graded exercise tests on a treadmill (Woodway, Pro Series, Waukesha, WI). Also, four high-speed runs to exhaustion were conducted at 110, 105, 100, and 90% of the treadmill velocity recorded during VO2max, and the distances achieved were plotted over the times-to-exhaustion. Linear regression was used to determine the slopes (critical velocity, CV) and y-intercepts (anaerobic running capacity, ARC) of these relationships to assess aerobic and anaerobic performances, respectively. Training volumes were tracked by summing the distances achieved during each training session for each subject. Percent body fat (%BF) and lean

  11. The effects of a pre-workout supplement containing caffeine, creatine, and amino acids during three weeks of high-intensity exercise on aerobic and anaerobic performance

    Directory of Open Access Journals (Sweden)

    Kendall Kristina L

    2010-02-01

    Full Text Available Abstract Background A randomized, single-blinded, placebo-controlled, parallel design study was used to examine the effects of a pre-workout supplement combined with three weeks of high-intensity interval training (HIIT on aerobic and anaerobic running performance, training volume, and body composition. Methods Twenty-four moderately-trained recreational athletes (mean ± SD age = 21.1 ± 1.9 yrs; stature = 172.2 ± 8.7 cm; body mass = 66.2 ± 11.8 kg, VO2max = 3.21 ± 0.85 l·min-1, percent body fat = 19.0 ± 7.1% were assigned to either the active supplement (GT, n = 13 or placebo (PL, n = 11 group. The active supplement (Game Time®, Corr-Jensen Laboratories Inc., Aurora, CO was 18 g of powder, 40 kcals, and consisted of a proprietary blend including whey protein, cordyceps sinensis, creatine, citrulline, ginseng, and caffeine. The PL was also 18 g of powder, 40 kcals, and consisted of only maltodextrin, natural and artificial flavors and colors. Thirty minutes prior to all testing and training sessions, participants consumed their respective supplements mixed with 8-10 oz of water. Both groups participated in a three-week HIIT program three days per week, and testing was conducted before and after the training. Cardiovascular fitness (VO2max was assessed using open circuit spirometry (Parvo-Medics TrueOne® 2400 Metabolic Measurement System, Sandy, UT during graded exercise tests on a treadmill (Woodway, Pro Series, Waukesha, WI. Also, four high-speed runs to exhaustion were conducted at 110, 105, 100, and 90% of the treadmill velocity recorded during VO2max, and the distances achieved were plotted over the times-to-exhaustion. Linear regression was used to determine the slopes (critical velocity, CV and y-intercepts (anaerobic running capacity, ARC of these relationships to assess aerobic and anaerobic performances, respectively. Training volumes were tracked by summing the distances achieved during each training session for each subject

  12. Response of aerobic rice to Piriformospora indica.

    Science.gov (United States)

    Das, Joy; Ramesh, K V; Maithri, U; Mutangana, D; Suresh, C K

    2014-03-01

    Rice cultivation under aerobic condition not only saves water but also opens up a splendid scope for effective application of beneficial root symbionts in rice crop unlike conventional puddled rice cultivation where water logged condition acts as constraint for easy proliferation of various beneficial soil microorganisms like arbuscular mycorrhizal (AM) fungi. Keeping these in view, an in silico investigation were carried out to explore the interaction of hydrogen phosphate with phosphate transporter protein (PTP) from P. indica. This was followed by greenhouse investigation to study the response of aerobic rice to Glomusfasciculatum, a conventional P biofertilizer and P. indica, an alternative to AM fungi. Computational studies using ClustalW tool revealed several conserved motifs between the phosphate transporters from Piriformospora indica and 8 other Glomus species. The 3D model of PTP from P. indica resembling "Mayan temple" was successfully docked onto hydrogen phosphate, indicating the affinity of this protein for inorganic phosphorus. Greenhouse studies revealed inoculation of aerobic rice either with P. indica, G. fasciculatum or both significantly enhanced the plant growth, biomass and yield with higher NPK, chlorophyll and sugar compared to uninoculated ones, P. indica inoculated plants being superior. A significantly enhanced activity of acid phosphatase and alkaline phosphatase were noticed in the rhizosphere soil of rice plants inoculated either with P. indica, G. fasciculatum or both, contributing to higher P uptake. Further, inoculation of aerobic rice plants with P. indica proved to be a better choice as a potential biofertilizer over mycorrhiza.

  13. Anaerobic and aerobic transformation of TNT

    Energy Technology Data Exchange (ETDEWEB)

    Kulpa, C.F. [Univ. of Notre Dame, IN (United States). Dept. of Biological Sciences; Boopathy, R.; Manning, J. [Argonne National Lab., IL (United States). Environmental Research Div.

    1996-12-31

    Most studies on the microbial metabolism of nitroaromatic compounds have used pure cultures of aerobic microorganisms. In many cases, attempts to degrade nitroaromatics under aerobic conditions by pure cultures result in no mineralization and only superficial modifications of the structure. However, mixed culture systems properly operated result in the transformation of 2,4,6-trinitrotoluene (TNT) and in some cases mineralization of TNT occurs. In this paper, the mixed culture system is described with emphasis on intermediates and the characteristics of the aerobic microbial process including the necessity for a co-substrate. The possibility of removing TNT under aerobic/anoxic conditions is described in detail. Another option for the biodegradation of TNT and nitroaromatics is under anaerobic, sulfate reducing conditions. In this instance, the nitroaromatic compounds undergo a series of reductions with the formation of amino compounds. TNT under sulfate reducing conditions is reduced to triaminotoluene presumably by the enzyme nitrite reductase, which is commonly found in many Desulfovibrio spp. The removal of nitro groups from TNT is achieved by a series of reductive reactions with the formation of ammonia and toluene by Desulfovibrio sp. (B strain). These metabolic processes could be applied to other nitroaromatic compounds like nitrobenzene, nitrobenzoic acids, nitrophenols, and aniline. The data supporting the anaerobic transformation of TNT under different growth condition are reviewed in this report.

  14. 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.

  15. Repeated administration of the GABAB receptor positive modulator BHF177 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine seeking in rats.

    Science.gov (United States)

    Vlachou, Styliani; Guery, Sebastien; Froestl, Wolfgang; Banerjee, Deboshri; Benedict, Jessica; Finn, M G; Markou, Athina

    2011-05-01

    γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA(B) receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA(B) receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with GABA(B) receptor agonists, GABA(B) receptor positive modulators are potentially improved therapeutic compounds for the treatment of drug dependence compared with agonists. We examined whether the acute effects of the GABA(B) receptor positive modulator N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177) on nicotine self-administration and food-maintained responding under a fixed-ratio 5 schedule of reinforcement were maintained after repeated administration. The effects of acute BHF177 administration on cue-induced nicotine- and food-seeking behavior, a putative animal model of relapse, were also examined. Repeated administration of BHF177 for 14 days decreased nicotine self-administration, with small tolerance observed during the last 7 days of treatment, whereas BHF177 minimally affected food-maintained responding. Acute BHF177 administration dose-dependently blocked cue-induced reinstatement of nicotine-, but not food-, seeking behavior after a 10-day extinction period. These results showed that BHF177 selectively blocked nicotine self-administration and prevented cue-induced reinstatement of nicotine seeking, with minimal effects on responding for food and no effect on cue-induced reinstatement of food seeking. Thus, GABA(B) receptor positive modulators could be useful therapeutics for the treatment of different aspects of nicotine dependence by facilitating smoking cessation by decreasing nicotine intake and preventing relapse to smoking in humans.

  16. 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.

  17. 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

  18. Nicotine Withdrawal; Measure Your Symptoms (Quiz)

    Science.gov (United States)

    ... Free Resources Medications Can Help You Quit Using Nicotine Replacement Therapy Busting NRT Myths Smokefree Phone Apps ... Withdrawal Understanding Withdrawal Quiz: How Strong is Your Nicotine Addiction? Quiz: What Are Your Withdrawal Symptoms? Dealing ...

  19. Electronic Nicotine Delivery Systems Key Facts Infographic

    Data.gov (United States)

    U.S. Department of Health & Human Services — Explore the Electronic Nicotine Delivery Systems Key Facts Infographic which outlines key facts related to electronic nicotine delivery systems (ENDS), including...

  20. 2,4-Dichlorophenoxyacetic acid (2,4-D) degradation promoted by nanoparticulate zerovalent iron (nZVI) in aerobic suspensions.

    Science.gov (United States)

    Correia de Velosa, Adriana; Pupo Nogueira, Raquel F

    2013-05-30

    Reactive species generated by Fe(0) oxidation promoted by O2 (catalyzed or not by ligands) are able to degrade contaminant compounds like the herbicide 2,4-dichlorophenoxyacetic acid. The degradation of 2,4-D was influenced by the concentrations of zero valent iron (ZVI) and different ligands, as well as by pH. In the absence of ligands, the highest 2,4-D degradation rate was obtained at pH 3, while the highest percentage degradation (50%) was achieved at pH 5 after 120 min of reaction. Among the ligands studied (DTPA, EDTA, glycine, oxalate, and citrate), only ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) significantly enhanced oxidation of 2,4-D. This increase in oxidation was observed at all pH values tested (including neutral to alkaline conditions), indicating the feasibility of the technique for treatment of contaminated water. In the presence of EDTA, the oxidation rate was greater at pH 3 than at pH 5 or 7. Increasing the EDTA concentration increased the rate and percentage of 2,4-D degradation, however increasing the Fe(0) concentration resulted in the opposite behavior. It was found that degradation of EDTA and 2,4-D occurred simultaneously, and that the new methodology avoided any 2,4-D removal by adsorption/coprecipitation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. introduction aerobic mesophilic bacteria associated with irish potato

    African Journals Online (AJOL)

    faecalis showed inhibitory activity due to the effect of organic acid against Erwinia sp. and Bacillus sp. (A ). The. 1 results indicated the high prevalence of antibiotic resistant strains associated with the spoilage of Irish potato. Key words: Irish Potato, Aerobic Mesophilic Bacteria, Antimicrobial Agents, Lactic Acid Bacteria,.

  2. 27 CFR 21.119 - Nicotine solution.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Nicotine solution. 21.119....119 Nicotine solution. (a) Composition. Five gallons of an aqueous solution containing 40 percent nicotine; 3.6 avoirdupois ounces of methylene blue, U.S.P.; water sufficient to make 100 gallons. (b) Color...

  3. 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

  4. Cellular and synaptic mechanisms of nicotine addiction

    NARCIS (Netherlands)

    Mansvelder, H.D.; McGehee, D.S.

    2002-01-01

    The tragic health effects of nicotine addiction highlight the importance of investigating the cellular mechanisms of this complex behavioral phenomenon. The chain of cause and effect of nicotine addiction starts with the interaction of this tobacco alkaloid with nicotinic acetylcholine receptors

  5. 21 CFR 172.310 - Aluminum nicotinate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Aluminum nicotinate. 172.310 Section 172.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Special Dietary and Nutritional Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be safely...

  6. Sequential anaerobic/aerobic biotreatment of bark leachate.

    Science.gov (United States)

    Frigon, J C; Cimpoia, R; Guiot, S R

    2003-01-01

    Bark leachate is generated from sawmill operations such as log storage sites and contains polymeric tannins, carbohydrates, organic acids, phenolic and resin compounds. The present study was aimed at assessing the performance of a sequential anaerobic and aerobic treatment, for both chemical oxygen demand (COD) and phenol removal, under various combinations of operational conditions, in the continuous mode. After anaerobic treatment in a five litres upflow anaerobic sludge bed (UASB) reactor, the leachate was directed into two parallel aerobic reactors, either an activated sludge unit or a fixed film submerged filter (packed with polyethylene Flexirings), both of a volume of one litre and oxygenated by air diffusion. For a leachate of 22 gCOD/l, an overall COD removal of 96-98% was achieved at an hydraulic residence time (HRT) of 4 days for the anaerobic reactor and one day for either aerobic systems. The phenol concentration generally increased after anaerobic treatment but was below the detection limit (50 ppb) after aerobic polishing. Radiorespirometric microcosms with 14C-labelled phenol confirmed that phenol was mineralized in the aerobic reactors. The performances of both aerobic systems were similar for COD and phenol removal. Thus, a sequential anaerobic/aerobic treatment was able to effectively address the contamination of a bark leachate discharge, including phenols.

  7. Nicotine psychopharmacology: policy and regulatory.

    Science.gov (United States)

    Henningfield, Jack E; Zeller, Mitch

    2009-01-01

    Powerful nerve agent, poison, addictive drug, or wonder medicine of the future? Nicotine has had a long and storied history in pharmacology, physiology, public health and, more recently, in regulatory policy initiatives in the United States and internationally. Psychopharmacology research on nicotine and tobacco came to particular prominence in the latter third of the twentieth century with exploration addressing the role of nicotine in tobacco use, the potential categorization of nicotine as an addictive drug, the pharmacological basis for treatment of tobacco addiction, and the perspective of policy developers seeking to reduce the toll of tobacco use. In fact, the 2005 ratification of the World Health Organization's first global health treaty, the Framework Convention on Tobacco Control, provides further impetus for extending the science foundation for tobacco disease control and policy efforts. Implementation of the treaty's provisions will control tobacco use and reduce the 500 million premature deaths projected to occur in the first half of the twenty-first century from tobacco use. Psychopharmacological research on nicotine and tobacco was important in the rationale and development of the treaty. The public health relevance of psychopharmacology research continues to grow with the realization of the potential of nicotine and related drugs to treat or prevent a diverse range of disorders (e.g., Alzheimer's disease, attention deficit hyperactivity disorder, and pain). Although comprehensive review of the research and implications is beyond the scope of this article, the more modest goal of providing insight into the theoretical, clinical, and policy importance of key psychopharmacology research laboratories over the past few decades is attempted.

  8. 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.

  9. Aerobic landfill bioreactor

    Science.gov (United States)

    Hudgins, Mark P; Bessette, Bernard J; March, John C; McComb, Scott T.

    2002-01-01

    The present invention includes a system of decomposing municipal solid waste (MSW) within a landfill by converting the landfill to aerobic degradation in the following manner: (1) injecting air via the landfill leachate collection system (2) injecting air via vertical air injection wells installed within the waste mass; (3) applying leachate to the waste mass using a pressurized drip irrigation system; (4) allowing landfill gases to vent; and (5) adjusting air injection and recirculated leachate to achieve a 40% to 60% moisture level and a temperature between 120.degree. F. and 140.degree. F. in steady state.

  10. Current Performance of an Aerobic Passive Wetlands Treating Acid Mine Drainage Flow From Underground Mine Seals at Moraine State Park, Butler County, Pennsylvania

    Science.gov (United States)

    Winter, J. A.; Fredrick, K.

    2008-12-01

    Coal mining was conducted in the area of Moraine State Park prior to the establishing the park and associated Lake Arthur. A total of 69 underground mine entries were sealed during the 1960's to the early 1970's along the proposed northern shore of Lake Arthur. Seals were constructed using a flyash/cement mixture that was pumped into boreholes to place bulkheads in the mine entries, then filling between the bulkheads, and injecting grout into the adjacent strata to form a grout curtain. During 1979 and 1980, a study was performed by the United States Department of the Interior, Bureau of Mines, to determine the long term effectiveness of the underground mine sealing and reclamation work. Not all seals were successful. One of these mine entry seals was leaking and depositing iron hydroxides on the shoreline. During 1995-96, a passive wetlands treatment system was designed and constructed to treat an acid mine drainage (amd) discharge emanating from one of these sealed mines. The system consists of a primary settling pond, a cattail vegetated pond, and a final polishing pond prior to discharge to Lake Arthur. The design life of the system was estimated at twelve years. After twelve years it was believed the precipitate in the ponds would need to be removed and the system rehabilitated to continue treating the amd discharge. A maintenance plan was considered, however only minimal maintaining of the area was implemented. Six sets of water quality samples were collected and analyzed for standard amd parameters of alkalinity, acidity, pH, iron, manganese, aluminum, sulfate, and total suspended solids. Precipitation data and flow rates were collected and an analysis was done to determine if flow varied seasonally. The water quality data was compared to flow and precipitation amounts. Sludge precipitate samples were collected from the first settling pond to estimate the deposition rate and to determine how long the ponds can continue to function before they would require

  11. 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.

  12. Pharmacology of niacin or nicotinic acid

    OpenAIRE

    Santos, Raul D.

    2005-01-01

    Niacina ou ácido nicotínico é uma vitamina solúvel com propriedades hipolipemiantes. Niacina reduz triglicérides (20% - 50%), LDL (5% - 25%), e aumenta HDL (15% - 35%). O estudo Coronary Drug Project mostrou que o uso de niacina foi associado com redução de eventos coronários e mortalidade total, e mais recentemente, foi demonstrado que niacina combinada com outras drogas hipolipemiantes pode atenuar a progressão da aterosclerose coronária. A niacina parece reduzir a mobilização de ácidos gra...

  13. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity

    Directory of Open Access Journals (Sweden)

    Zulezwan A. Malik

    2013-12-01

    Full Text Available Two-dimensional gel electrophoresis provides robust comparative analysis of skeletal muscle, but this technique is laborious and limited by its inability to resolve all proteins. In contrast, orthogonal separation by SDS-PAGE and reverse-phase liquid chromatography (RPLC coupled to mass spectrometry (MS affords deep mining of the muscle proteome, but differential analysis between samples is challenging due to the greater level of fractionation and the complexities of quantifying proteins based on the abundances of their tryptic peptides. Here we report simple, semi-automated and time efficient (i.e., 3 h per sample proteome profiling of skeletal muscle by 1-dimensional RPLC electrospray ionisation tandem MS. Solei were analysed from rats (n = 5, in each group bred as either high- or low-capacity runners (HCR and LCR, respectively that exhibited a 6.4-fold difference (1,625 ± 112 m vs. 252 ± 43 m, p < 0.0001 in running capacity during a standardized treadmill test. Soluble muscle proteins were extracted, digested with trypsin and individual biological replicates (50 ng of tryptic peptides subjected to LC-MS profiling. Proteins were identified by triplicate LC-MS/MS analysis of a pooled sample of each biological replicate. Differential expression profiling was performed on relative abundances (RA of parent ions, which spanned three orders of magnitude. In total, 207 proteins were analysed, which encompassed almost all enzymes of the major metabolic pathways in skeletal muscle. The most abundant protein detected was type I myosin heavy chain (RA = 5,843 ± 897 and the least abundant protein detected was heat shock 70 kDa protein (RA = 2 ± 0.5. Sixteen proteins were significantly (p < 0.05 more abundant in HCR muscle and hierarchal clustering of the profiling data highlighted two protein subgroups, which encompassed proteins associated with either the respiratory chain or fatty acid oxidation. Heart-type fatty acid binding protein (FABPH was 1

  14. Differential responses of hippocampal neurons and astrocytes to nicotine and hypoxia in the fetal guinea pig.

    Science.gov (United States)

    Blutstein, Tamara; Castello, Michael A; Viechweg, Shaun S; Hadjimarkou, Maria M; McQuail, Joseph A; Holder, Mary; Thompson, Loren P; Mong, Jessica A

    2013-07-01

    In utero exposure to cigarette smoke has severe consequences for the developing fetus, including increased risk of birth complications and behavioral and learning disabilities later in life. Evidence from animal models suggests that the cognitive deficits may be a consequence of in utero nicotine exposure in the brain during critical developmental periods. However, maternal smoking exposes the fetus to not only nicotine but also a hypoxic intrauterine environment. Thus, both nicotine and hypoxia are capable of initiating cellular cascades, leading to long-term changes in synaptic patterning that have the potential to affect cognitive functions. This study investigates the combined effect of in utero exposure to nicotine and hypoxia on neuronal and glial elements in the hippocampal CA1 field. Fetal guinea pigs were exposed in utero to normoxic or hypoxic conditions in the presence or absence of nicotine. Hypoxia increased the protein levels of matrix metalloproteinase-9 (MMP-9) and synaptophysin and decreased the neural density as measured by NeuN immunoreactivity (ir). Nicotine exposure had no effect on these neuronal parameters but dramatically increased the density of astrocytes immunopositive for glial fibrillary acidic protein (GFAP). Further investigation into the effects of in utero nicotine exposure revealed that both GFAP-ir and NeuN-ir in the CA1 field were significantly reduced in adulthood. Taken together, our data suggest that prenatal exposure to nicotine and hypoxia not only alters synaptic patterning acutely during fetal development, but that nicotine also has long-term consequences that are observed well into adulthood. Moreover, these effects most likely take place through distinct mechanisms.

  15. Smoking, nicotine and the kidney

    NARCIS (Netherlands)

    Agarwal, Pramod Kumar

    2012-01-01

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

  16. Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia and airway mucus formation in vitro and in vivo

    Science.gov (United States)

    Gundavarapu, Sravanthi; Wilder, Julie A.; Mishra, Neerad C.; Rir-sima-ah, Jules; Langley, Raymond J.; Singh, Shashi P.; Saeed, Ali Imran; Jaramillo, Richard J.; Gott, Katherine M.; Peña-Philippides, Juan Carlos; Harrod, Kevin S.; McIntosh, J. Michael; Buch, Shilpa; Sopori, Mohan L.

    2012-01-01

    Background Airway mucus hypersecretion is a key pathophysiological feature in number of lung diseases. Cigarette smoke/nicotine and allergens are strong stimulators of airway mucus; however, the mechanism of mucus modulation is unclear. Objectives Characterize the pathway by which cigarette smoke/nicotine regulates airway mucus and identify agents that decrease airway mucus. Methods IL-13 and gamma-aminobutyric acid receptors (GABAARs) are implicated in airway mucus. We examined the role of IL-13 and GABAARs in nicotine-induced mucus formation in normal human bronchial epithelial (NHBE) and A549 cells, and secondhand cigarette smoke and/or ovalbumin-induced mucus formation in vivo. Results Nicotine promotes mucus formation in NHBE cells; however, the nicotine-induced mucus formation is independent of IL-13 but sensitive to the GABAAR antagonist picrotoxin (PIC). Airway epithelial cells express α7/α9/α10 nicotinic acetylcholine receptors (nAChRs) and specific inhibition or knockdown of α7- but not α9/α10-nAChRs abrogates mucus formation in response to nicotine and IL-13. Moreover, addition of acetylcholine or inhibition of its degradation increases mucus in NHBE cells. Nicotinic but not muscarinic receptor antagonists block allergen or nicotine/cigarette smoke-induced airway mucus formation in NHBE cells and/or in mouse airways. Conclusions Nicotine-induced airway mucus formation is independent of IL-13 and α7-nAChRs are critical in airway mucous cell metaplasia/hyperplasia and mucus production in response to various pro-mucoid agents, including IL-13. In the absence of nicotine, acetylcholine may be the biological ligand for α7-nAChRs to trigger airway mucus formation. α7-nAChRs are downstream of IL-13 but upstream of GABAARα2 in the MUC5AC pathway. Acetylcholine and α-7-nAChRs may serve as therapeutic targets to control airway mucus. PMID:22578901

  17. Anti-inflammatory and antithrombotic effects of nicotine exposure in oral contraceptive-induced insulin resistance are glucocorticoid-independent.

    Science.gov (United States)

    Olatunji, Lawrence Aderemi; Michael, Olugbenga Samuel; Adeyanju, Oluwaseun Aremu; Areola, Emmanuel Damilare; Soladoye, Ayodele Olufemi

    2017-06-01

    Reports showed that estrogen-progestin oral contraceptive (COC) or tobacco smoking causes increased risk of cardiovascular diseases (CVD) in premenopausal women. Studies also suggest that nicotine, a major tobacco alkaloid, may worsen or improve atherothrombotic CVD. Altered hemorheology, prothrombotic and pro-inflammatory biomarkers, have been implicated in the development of atherothrombotic CVD events. However, the effect of non-smoking nicotine exposure on these biomarkers during COC treatment is not yet established. We therefore sought to determine the effects of nicotine exposure during COC treatment on these biomarkers, and also tested the hypothesis that the nicotine effects would be glucocorticoid-dependent. Female Sprague-Dawley rats aged 10 weeks were given (po) vehicle, low-dose nicotine (0.1mg/kg) or high-dose nicotine (1.0mg/kg) with or without COC steroids (5.0μg/kg ethinylestradiol and 25.0μg/kg levonorgestrel) daily for 6 weeks. COC treatment or nicotine exposure led to increased insulin resistance (IR), hemorheological (blood viscosity, hematocrit and plasma viscosity), prothrombotic (plasminogen activator inhibitor-1), pro-inflammatory (uric acid, C-reactive protein, neutrophil/lymphocyte and platelet/lymphocyte ratios) biomarkers and corticosterone. However, these effects except that on corticosterone were abrogated by nicotine exposure during COC treatment. Our study indicates that nicotine- or COC-induced IR may be mediated via inflammatory/thrombotic pathway. The results imply that nicotine exposure could impact negatively on atherothrombotic biomarkers in COC non-users, whereas the impact in COC users could be positive. The results also suggest that the anti-inflammatory, antithrombotic and blood viscosity-lowering effects of nicotine exposure during COC use is circulating glucocorticoid-independent. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  18. Nicotine behavioral pharmacology: clues from planarians.

    Science.gov (United States)

    Rawls, Scott M; Patil, Tanvi; Tallarida, Christopher S; Baron, Steven; Kim, Myongji; Song, Kevin; Ward, Sara; Raffa, Robert B

    2011-11-01

    Nicotine is one of the world's most addictive substances and the primary reason that humans inhale tobacco smoke. The pharmacological effects of nicotine can be investigated in planarians, aquatic flatworms that possess an integrated neural network including cephalic ganglia that some consider the earliest 'brain' and spinal cord. Here, we tested the hypothesis that nicotine exposure elicits mammalian-like behaviors in planarians. Planarian motility and stereotypy (C-shape hyperkinesias) were quantified following acute nicotine exposure. During repeated nicotine exposure, we investigated the presence of withdrawal, tolerance, behavioral sensitization, and environmental place conditioning. Acute nicotine exposure increased stereotypical activity and elicited biphasic effects on motility. A low concentration (0.01 mM) increased motility whereas higher concentrations (0.3-10mM) elicited the opposite effect. Planarians exposed to nicotine (0.03 mM) for 60 min and then tested in water displayed reduced motility that was not observed during exposure to water, acute nicotine, or continuous nicotine. Nicotine-treated planarians withdrawn from the drug for 3 days before being challenged with nicotine displayed behavioral sensitization at low concentrations (0.1, 0.3mM) but tolerance at higher concentrations (1, 3mM). Planarians conditioned with nicotine in the ambient light (non-preferred environment) displayed a reduction in their natural preference for a dark environment. The present results suggest nicotine elicits mammalian-like effects in planarians, including decreased motility and increased stereotypy following acute administration and abstinence-induced withdrawal, behavioral sensitization, tolerance, and place conditioning during repeated exposure. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Phospholipase C activity affinity purifies with the Torpedo nicotinic acetylcholine receptor.

    Science.gov (United States)

    Labriola, Jonathan M; daCosta, Corrie J B; Wang, Shuzhi; Figeys, Daniel; Smith, Jeffrey C; Sturgeon, R Michel; Baenziger, John E

    2010-04-02

    Nicotinic acetylcholine receptors mediate fast synaptic transmission by fluxing ions across the membrane in response to neurotransmitter binding. We show here that during affinity purification of the nicotinic acetylcholine receptor from Torpedo, phosphatidic acid, but not other anionic or zwitterionic phospholipids, is hydrolyzed to diacylglycerol. The phospholipase C activity elutes with the acetylcholine receptor and is inhibited by a lipid phosphate phosphohydrolase inhibitor, sodium vanadate, but not a phosphatidate phosphohydrolase inhibitor, N-ethylmaleimide. Further, the hydrolysis product of phosphatidic acid, diacylglycerol, enhances the functional capabilities of the acetylcholine receptor in the presence of anionic lipids. We conclude that a phospholipase C activity, which appears to be specific for phosphatidic acid, is associated with the nicotinic acetylcholine receptor. The acetylcholine receptor may directly or indirectly influence lipid metabolism in a manner that enhances its own function.

  20. 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)

  1. Effects of nicotine on cellular proliferation, macromolecular synthesis and cell cycle phase distribution in human and murine cells

    International Nuclear Information System (INIS)

    Konno, S.; Chiao, J.; Rossi, J.; Wang, C.H.; Wu, J.M.

    1986-01-01

    Addition of nicotine causes a dose- and time-dependent inhibition of cell growth in established human and murine cells. In the human promyelocytic HL-60 leukemic cells, 3 mM nicotine results in a 50% inhibition of cellular proliferation after 80 h. Nicotine was also found to affect the cell cycle distribution of HL-60 cells. Treatment with 4 mM nicotine for 20 h causes an increase in proportion of Gl-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 cell arrest in the Gl-phase which may in part account for its effects on cell growth. To determine whether nicotine has a primary effect on the uptake/transport of macromolecular precursors into cells, HL-60 cells were treated with 2-6 mM nicotine for 30 h 3 at the end of which time cells were labeled with [ 3 H]thymidine, [ 3 H]uridine, [ 14 C]lysine and [ 35 S]methionine, the trichloroacetic acid (TCA) soluble and insoluble radioactivities from each of the labeling conditions were determined. These studies show that nicotine primarily affect the synthesis of proteins

  2. Protective effects of Mentha spicata against nicotine-induced toxicity in liver and erythrocytes of Wistar rats.

    Science.gov (United States)

    Ben Saad, Anouar; Rjeibi, Ilhem; Alimi, Hichem; Ncib, Sana; Bouhamda, Talel; Zouari, Nacim

    2018-01-01

    The aim of this study was to investigate the protective effect of Mentha spicata supplementation against nicotine-induced oxidative damage in the liver and erythrocytes of Wistar rats. Bioactive substances were determined by liquid chromatography - electrospray ionization - tandem mass spectrometry analysis. Animals were divided into 4 groups of 6 rats each: a normal control group, a nicotine-treated group (1 mg/kg), a group receiving M. spicata extract (100 mg/kg), and a group receiving both M. spicata extract (100 mg/kg) and nicotine (1 mg/kg). Many phenolic acids were identified in the M. spicata aqueous extract. After 2 months of treatment, nicotine induced an increase in the level of white blood cells and a marked decrease in erythrocytes, hemoglobin, and haematocrit. Aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase activities were also found to be higher in nicotine-treated group than those of the control group. Furthermore, nicotine-treated rats exhibited oxidative stress, as evidenced by a decrease in antioxidant enzymes activities and an increase in lipid peroxidation level in liver and erythrocytes. Interestingly, the oral administration of M. spicata extract by nicotine-treated rats alleviated such disturbances. M. spicata contained bioactive compounds that possess important antioxidant potential and protected liver and erythrocytes against nicotine-induced damage.

  3. Reinforcing effectiveness of nicotine in nonhuman primates: Effects of nicotine dose and history of nicotine self-administration

    Science.gov (United States)

    Kohut, Stephen J.; Bergman, Jack

    2016-01-01

    Rationale Despite the high prevalence of nicotine use in humans, robust nicotine self-administration has been difficult to demonstrate in laboratory animals. Objectives A parametric analysis of nicotine self-administration was conducted to study its reinforcing effects in non-human primates. Methods Adult rhesus macaques (N=6) self-administered intravenous (IV) nicotine (0.001-0.1 mg/kg) under a fixed ratio (FR) 1 schedule of reinforcement during daily 90-min sessions. Next, the demand function relating drug intake and response cost was determined by increasing the FR across sessions during the availability of each of several unit doses of nicotine (0.0032-0.032 mg/kg/inj). The reinforcing effects of 0.01 mg/kg/inj cocaine and 1-g banana-flavored food pellets were also determined under similar testing conditions. Finally, the nicotine demand function was re-determined after approximately 8 months of daily IV nicotine self-administration. Results IV nicotine self-administration followed an inverted-U shaped pattern, with the peak number of injections maintained by 0.0032 mg/kg/inj. Self-administration of each reinforcer (food pellets, IV cocaine, and IV nicotine) decreased as FR size increased. Application of the exponential model of demand showed that the demand elasticity for nicotine was: 1) dose-dependent and lowest for 0.0032 mg/kg/inj); 2) for 0.0032 mg/kg/inj, similar to that of food pellets and significantly higher than cocaine; and 3) decreased after 8 months of daily nicotine self-administration. Conclusions These data show that, though high levels of nicotine self-administration can be achieved under simple FR schedules in nonhuman primates, its reinforcing effectiveness is dose-related but limited, and may increase over time. PMID:27076210

  4. Nicotine and acute stress: effects of nicotine versus nicotine withdrawal on stress-induced hemoconcentration and cardiovascular reactivity.

    Science.gov (United States)

    Vanderkaay, Melissa M; Patterson, Stephen M

    2006-02-01

    This study was designed to assess the effects of nicotine and nicotine withdrawal on stress-induced hemoconcentration and cardiovascular reactivity during acute stress in smokers. Forty-six smokers (>or=10 cigarettes per day) were tested twice, once while wearing a 21 mg nicotine patch for 12h and once while wearing a placebo patch (nicotine withdrawal). Calculated plasma volume, hemoglobin, hematocrit, HR, SBP, DBP, cardiac output, stroke volume, and total peripheral resistance were assessed during a 10-min baseline period, 6-min Paced Auditory Serial-Addition Task (PASAT), and a 2-min cold pressor (CP). No differences between conditions were found for any of the hematological measurements. Participants demonstrated greater HR and SBP increases to the PASAT during the nicotine withdrawal condition. For CP, participants showed greater HR and DBP increases and SV decreases during the nicotine withdrawal condition. Data from affective state ratings indicated that participants reported more negative affect during the psychological challenges during nicotine withdrawal conditions. Negative affective state may further lead to enhanced cardiovascular reactivity. These results demonstrate that although nicotine and nicotine withdrawal significantly have differential effects on cardiovascular functioning, the same differential condition effects do not appear to exist for stress-induced hemoconcentration.

  5. Energy efficient aerobic treatment of forest industry wastewaters; Energieffektiv aerob rening av skogsindustriella avloppsvatten

    Energy Technology Data Exchange (ETDEWEB)

    Sandberg, Maria; From-Aldaron, Mattias

    2011-01-15

    There is great potential to reduce energy requirements in aerobic biological purification if the oxygen demand can be reduced and oxygen delivery, when process water is aerated, is made more efficient. A model was developed to estimate the possible reduction in oxygen demand. Model variables were COD reduction, sludge withdrawal, oxygen, and alpha-value. Attempts made in an aerator in the lab-scale process shows that water content strongly affects oxygen transport and alpha-value. Surface active extract substances such as fatty acids and resin acids have greatest significance. The effect increases with the concentration of extract substances and decreases with added sodium chloride content

  6. Nicotinic Cholinergic Synaptic Mechanisms in the Ventral Tegmental Area Contribute to Nicotine Addiction

    Science.gov (United States)

    Pidoplichko, Volodymyr I.; Noguchi, Jun; Areola, Oluwasanmi O.; Liang, Yong; Peterson, Jayms; Zhang, Tianxiang; Dani, John A.

    2004-01-01

    Tobacco use is a major health problem that is estimated to cause 4 million deaths a year worldwide. Nicotine is the main addictive component of tobacco. It acts as an agonist to activate and desensitize nicotinic acetylcholine receptors (nAChRs). A component of nicotine's addictive power is attributable to actions on the mesolimbic dopaminergic…

  7. 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.

  8. Systematic unraveling of the unsolved pathway of nicotine degradation in Pseudomonas.

    Directory of Open Access Journals (Sweden)

    Hongzhi Tang

    2013-10-01

    Full Text Available Microorganisms such as Pseudomonas putida play important roles in the mineralization of organic wastes and toxic compounds. To comprehensively and accurately elucidate key processes of nicotine degradation in Pseudomonas putida, we measured differential protein abundance levels with MS-based spectral counting in P. putida S16 grown on nicotine or glycerol, a non-repressive carbon source. In silico analyses highlighted significant clustering of proteins involved in a functional pathway in nicotine degradation. The transcriptional regulation of differentially expressed genes was analyzed by using quantitative reverse transcription-PCR. We observed the following key results: (i The proteomes, containing 1,292 observed proteins, provide a detailed view of enzymes involved in nicotine metabolism. These proteins could be assigned to the functional groups of transport, detoxification, and amino acid metabolism. There were significant differences in the cytosolic protein patterns of cells growing in a nicotine medium and those in a glycerol medium. (ii The key step in the conversion of 3-succinoylpyridine to 6-hydroxy-3-succinoylpyridine was catalyzed by a multi-enzyme reaction consisting of a molybdopeterin binding oxidase (spmA, molybdopterin dehydrogenase (spmB, and a (2Fe-2S-binding ferredoxin (spmC with molybdenum molybdopterin cytosine dinucleotide as a cofactor. (iii The gene of a novel nicotine oxidoreductase (nicA2 was cloned, and the recombinant protein was characterized. The proteins and functional pathway identified in the current study represent attractive targets for degradation of environmental toxic compounds.

  9. Acclimation of aerobic-activated sludge degrading benzene derivatives and co-metabolic degradation activities of trichloroethylene by benzene derivative-grown aerobic sludge.

    Science.gov (United States)

    Wang, Shizong; Yang, Qi; Bai, Zhiyong; Wang, Shidong; Wang, Yeyao; Nowak, Karolina M

    2015-01-01

    The acclimation of aerobic-activated sludge for degradation of benzene derivatives was investigated in batch experiments. Phenol, benzoic acid, toluene, aniline and chlorobenzene were concurrently added to five different bioreactors which contained the aerobic-activated sludge. After the acclimation process ended, the acclimated phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic-activated sludge were used to explore the co-metabolic degradation activities of trichloroethylene (TCE). Monod equation was employed to simulate the kinetics of co-metabolic degradation of TCE by benzene derivative-grown sludge. At the end of experiments, the mixed microbial communities grown under different conditions were identified. The results showed that the acclimation periods of microorganisms for different benzene derivatives varied. The maximum degradation rates of TCE for phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic sludge were 0.020, 0.017, 0.016, 0.0089 and 0.0047 mg g SS(-1) h(-1), respectively. The kinetic of TCE degradation in the absence of benzene derivative followed Monod equation well. Also, eight phyla were observed in the acclimated benzene derivative-grown aerobic sludge. Each of benzene derivative-grown aerobic sludge had different microbial community composition. This study can hopefully add new knowledge to the area of TCE co-metabolic by mixed microbial communities, and further the understanding on the function and applicability of aerobic-activated sludge.

  10. 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...

  11. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review.

    Science.gov (United States)

    Sørensen, Lars Tue

    2012-06-01

    The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved. Smoking is a recognized risk factor for healing complications after surgery, but the pathophysiological mechanisms remain largely unknown. Pathophysiological studies addressing smoking and wound healing were identified through electronic databases (PubMed, EMBASE) and by hand-search of articles' bibliography. Of the 1460 citations identified, 325 articles were retained following title and abstract reviews. In total, 177 articles were included and systematically reviewed. Smoking decreases tissue oxygenation and aerobe metabolism temporarily. The inflammatory healing response is attenuated by a reduced inflammatory cell chemotactic responsiveness, migratory function, and oxidative bactericidal mechanisms. In addition, the release of proteolytic enzymes and inhibitors is imbalanced. The proliferative response is impaired by a reduced fibroblast migration and proliferation in addition to a downregulated collagen synthesis and deposition. Smoking cessation restores tissue oxygenation and metabolism rapidly. Inflammatory cell response is reversed in part within 4 weeks, whereas the proliferative response remains impaired. Nicotine does not affect tissue microenvironment, but appears to impair inflammation and stimulate proliferation. Smoking has a transient effect on the tissue microenvironment and a prolonged effect on inflammatory and reparative cell functions leading to delayed healing and complications. Smoking cessation restores the tissue microenvironment rapidly and the inflammatory cellular functions within 4 weeks, but the proliferative response remain impaired. Nicotine and nicotine replacement drugs seem to attenuate inflammation and enhance proliferation but the effect appears to be marginal.

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

    Science.gov (United States)

    Grebenstein, Patricia E.; Burroughs, Danielle; Roiko, Samuel A.; Pentel, Paul R.; LeSage, Mark G.

    2015-01-01

    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

  13. 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

  14. 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

  15. 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)

  16. 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.

  17. Passive immunization with a nicotine-specific monoclonal antibody decreases brain nicotine levels but does not precipitate withdrawal in nicotine-dependent rats

    OpenAIRE

    Roiko, Samuel A.; Harris, Andrew C.; LeSage, Mark G.; Keyler, Daniel E.; Pentel, Paul R.

    2009-01-01

    Vaccination against nicotine is under investigation as a treatment for tobacco dependence. Passive immunization with nicotine-specific antibodies represents a complementary strategy to vaccination. A potential adverse effect of passive immunization in nicotine-dependent individuals is that it may lead to a rapid reduction in brain nicotine levels and trigger withdrawal. The goal of this study was to determine if passive immunization with the nicotine-specific monoclonal antibody Nic311 precip...

  18. 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.

  19. Nicotine synthesis in Nicotiana tabacum L. induced by mechanical wounding is regulated by auxin.

    Science.gov (United States)

    Shi, Qiumei; Li, Chunjian; Zhang, Fusuo

    2006-01-01

    The effects of different kinds of mechanical wounding on nicotine production in tobacco plants were compared, with sand or hydroponics culture under controlled conditions. Both removal of the shoot apex and damage of the youngest unfolded leaves nos 1 and 2 by a comb-like brusher with 720 punctures caused an increase in nicotine concentration in whole plants at day 3, and reached its highest level at day 6. The nicotine concentration induced by excision of the shoot apex was much higher than that induced by leaf wounding. Both treatments also caused an increase in jasmonic acid (JA) concentration within 90 min in the shoot, followed by an increase in the roots (210 min), in which the JA concentration induced by leaf wounding was significantly higher than that induced by excision of the shoot apex. The increase in nicotine concentration occurred throughout the whole plant, especially in the shoot, while the increase in JA concentration in the shoot was restricted to the damaged tissues, and was not observed in the adjacent tissues. Removal of the lateral buds that emerged after excision of the shoot apex caused a further increase in nicotine concentrations in the plant tissues. Removal of mature leaves, however, did not cause any changes in nicotine concentration in the plant, even though the degree of wounding in this case was comparable with that occurring with apex removal. The results suggest that the nicotine production in tobacco plants was not correlated with the degree of wounding (cut-surface or punctures), but was highly dependent on the removal of apical meristems and hence on the major sources of auxin in the plant. Furthermore, immediate application of 1-naphthylacetic acid (NAA) on the cut surface after removing the shoot apex completely inhibited the increase both in nicotine in whole plants and in JA in the damaged stem segment and roots. Application of an auxin transport inhibitor around the stem directly under the shoot apex of intact plants also

  20. 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.

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

    African Journals Online (AJOL)

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

  2. VOLTAMMETRIC DETERMINATION OF NICOTINE IN CIGARETTE ...

    African Journals Online (AJOL)

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

  3. 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

  4. Nicotine does not enhance basic semantic priming.

    Science.gov (United States)

    Holmes, Anna D; Chenery, Helen J; Copland, David A

    2010-08-01

    Utilising a cognitively demanding strategy-based priming paradigm, we recently observed that acute transdermal nicotine selectively influenced controlled semantic processing but not related-word links within semantic memory per se as reported by Holmes et al. (Int J Neuropsychopharmacol 11:389-399, 2008). The current study employed a less cognitively demanding priming paradigm to investigate whether nicotine influences the activation/access of links within semantic memory, and if the selective nicotinic influence on controlled but not automatic semantic processing could also be observed with these more general priming procedures. Transdermal nicotine patches (7 mg/24 h) were administered to healthy young adults in a double-blind, placebo-controlled, crossover design. The automatic priming task ( n = 18) had a low relatedness proportion (RP) and was presented at a short stimulus onset asynchrony (SOA), while the controlled priming task ( n = 18) had a high RP and long SOA. The patterns of priming effects indicated that automatic and controlled processing were operating for the respective tasks. However, a nicotinic influence on semantic processing was not evident for either task, nor was interplay of nicotine and relatedness observed. Together, the findings from the previous and current study suggest that an influence of nicotine on semantic processing may only emerge when effortful controlled processing is invoked. Furthermore, the findings suggest that nicotinic modulation of links within semantic memory may only be mediated by mnemonic processes.

  5. Personality types and nicotine dependency among medical ...

    African Journals Online (AJOL)

    Personality types and nicotine dependency among medical sciences students. ... Internet Journal of Medical Update - EJOURNAL ... the students were smokers and 82.5% (330) nonsmokers; moreover, our results showed 66.7% (47) of smokers had low dependency and 33.3% (23) were physically dependent on nicotine.

  6. 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.

  7. Alcohol's actions on neuronal nicotinic acetylcholine receptors.

    Science.gov (United States)

    Davis, Tiffany J; de Fiebre, Christopher M

    2006-01-01

    Although it has been known for many years that alcoholism and tobacco addiction often co-occur, relatively little information is available on the biological factors that regulate the co-use and abuse of nicotine and alcohol. In the brain, nicotine acts at several different types of receptors collectively known as nicotinic acetylcholine receptors (nAChRs). Alcohol also acts on at least some of these receptors, enhancing the function of some nAChR subtypes and inhibiting the activity of others. Chronic alcohol and nicotine administration also lead to changes in the numbers of nAChRs. Natural variations (i.e., polymorphisms) in the genes encoding different nAChR subunits may be associated with individual differences in the sensitivity to some of alcohol's and nicotine's effects. Finally, at least one subtype of nAChR may help protect cells against alcohol-induced neurotoxicity.

  8. 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.

  9. Molecular Determinants of α3β4 Nicotinic Acetylcholine Receptors Inhibition by Triterpenoids.

    Science.gov (United States)

    Eom, Sanung; Kim, Yoon Suh; Lee, Sung Bae; Noh, Shinhwa; Yeom, Hye Duck; Bae, Hyunsu; Lee, Jun-Ho

    2018-01-01

    In a previous work, we reported the regulatory role of the triterpenoids on 5-hydroxytryptamine (5-HT) 3 A receptors activity in Xenopus laevis oocytes (Eur. J. Pharmacol., 615, 2009, Lee et al.). In the present report, we studied the modulation of triterpenoids on the activity of the human nicotinic acetylcholine receptor type α3β4. Two-electrode voltage clamp experiments were used to test acetylcholine mediated inward current (I ACh ). Treatment with triterpenoids (dehydroeburicoic acid, 6α-hydroxypolyporenic acid C and pachymic acid) inhibited I ACh in a concentration dependent and reversible manner. The IC 50 values for pachymic acid, dehydroeburicoic acid, and 6α-hydroxypolyporenic acid C were 14.9, 37.7, and 20.9 µM, respectively. The inhibitory regulation of I ACh by each triterpenoid showed in a non-competitive manner on the activity of α3β4 nicotinic acetylcholine receptors. These results show that triterpenoids (pachymic acid, dehydroeburicoic acid, 6α-hydroxypolyporenic acid C) can be used as agents to modulate the activity of nicotinic acetylcholine receptor type α3β4. Furthermore, molecular docking studies of 6α-hydroxypolyporenic acid C on α3β4 nicotinic acetylcholine receptors in silico showed that this molecule interacted predominantly with residues at cavities in the α3 subunit and β4 subunit. This docking assays indicated four potential binding sites for this ligand in the extracellular region at sensor domain of α3β4 nicotinic acetylcholine receptors. In point mutagenesis of those whose alanine substitution, 6α-hydroxypolyporenic acid C potency decreased on W25A of α3 subunit or N109A of β4 subunit in both mutants. The double mutation of W25A of α3 subunit and N109A of β4 subunit was significantly attenuated inhibitory effects by 6α-hydroxypolyporenic acid C. All taken together, this study revealed that molecular basis of α3β4 nicotinic acetylcholine receptors by triterpenoids and provides a novel potent interaction

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

    African Journals Online (AJOL)

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

  11. Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors.

    NARCIS (Netherlands)

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

    2015-01-01

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

  12. 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

  13. [Drugs used to treat nicotine addiction].

    Science.gov (United States)

    Zieleń, Iwona; Sliwińska-Mossoń, Mariola; Milnerowicz, Halina

    2012-01-01

    Tobacco smoking in Poland is fairly widespread on a large scale. Research suggests that the early twenty-first century, the percentage of female daily smokers aged 20 and above was 26%, and men the same age 43%. In addition, epidemiological studies have shown that smoking was the cause of approximately sixty-nine thousand deaths in Poland (including fifty-seven thousand men and twelve thousand women). It is common ground that cigarette smoking has a negative effect on our body. It represents one of the main and most commonly defined risk factors for many diseases that can be eliminated. Smoking often leads to addiction, and nicotine is an addictive drug. Nicotine addiction is characterized by symptoms such as: "hunger" smoking, difficulty in controlling behavior on smoking or the number of cigarettes smoked, nicotine withdrawal, the occurrence of tolerance, neglect of interests, as well as devoting more time on activities related to smoking, follow-up smoking despite knowledge of its dangers. The most commonly used in Poland, a questionnaire to identify nicotine dependence is a test Fagerstöma. Currently assigned some importance, "the doctor a conversation the patient" and motivating him to stop smoking and maintain abstinence as long as possible. But beyond the "conversation" is also used as an aid to medical treatment for the patient to stop smoking, especially to alleviate withdrawal symptoms. The first attempts of pharmacological help in the effort to weaning from smoking began in the thirties. Were conducted fairly successful, although uncontrolled trials with lobeline, an alkaloid of action similar to nicotine. In Poland, the drugs of first choice in the treatment of nicotine dependence are nicotine replacement therapies (nicotine gum and patches that contain nicotine) and bupropion SR. Quite a popular drugs to help in the fight against addiction are also cytisine and varenicline. The choice of the drug is usually the result of medical experience in the use

  14. Quantification of Nicotine in Commercial Brand Cigarettes: How Much Is Inhaled by the Smoker?

    Science.gov (United States)

    Vieira, Carlos A.; de Paiva, Sabina A. A.; Funai, Milena N. S.; Bergamaschi, Mateus M.; Queiroz, Regina H. C.; Giglio, Jose R.

    2010-01-01

    The main objective of this experiment is to determine the amount of nicotine in commercial brand cigarettes by means of a nonaqueous acid-base titration. A simple glass device simulating a smoker is proposed, which allows the determination of the volatilized, filter retained, and inhaled portions. Students will readily see that the amount of…

  15. Non-catalytic oxidation of water-slurried coal with oxygen: Identification of fulvic acids and acute toxicity

    CSIR Research Space (South Africa)

    Bergh, JJ

    1997-01-01

    Full Text Available Methylmalonic acid X 4-Hydroxybutyric acid X X X 3-Hydroxypropionic acid X Benzoic acid X X X Isonicotinic acid X Nicotinic acid X X Acetoacetic acid X X Succinic acid X X X X X Methylsuccinic acid X X X Itaconic acid X... of similarity, and most of these compounds were also present in the steam distillate. Significant additions were thymol (2-isopropyl-5-methylphenol, which occurs naturally in many essential oils) and the nitrogen compounds nicotinic...

  16. Positive modulation of GABA(B) receptors decreased nicotine self-administration and counteracted nicotine-induced enhancement of brain reward function in rats.

    Science.gov (United States)

    Paterson, Neil E; Vlachou, Styliani; Guery, Sebastien; Kaupmann, Klemens; Froestl, Wolfgang; Markou, Athina

    2008-07-01

    Acute administration of gamma-aminobutyric acid (GABA)-B receptor agonists decreases nicotine, cocaine, ethanol, and heroin self-administration and also decreases food-maintained responding and suppresses locomotor activity at high doses. GABA(B) receptor-positive modulators may represent potentially improved therapeutic compounds because of their fewer side effects than receptor agonists. The present study investigated the effects of administration of the GABA(B) receptor-positive modulators 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177) and coadministration of the GABA(B) receptor-positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) with the GABA(B) receptor agonist (3-amino-2[S]-hydroxypropyl)-methylphosphinic acid (CGP44532) on nicotine- and food-maintained responding under fixed ratio (FR) 5 and progressive ratio schedules of reinforcement. Furthermore, the effects of BHF177 and CGP44532 on nicotine-induced enhancement of brain reward function were evaluated. The results indicated that administration of CGP7930 decreased nicotine self-administration under an FR5 schedule. Administration of either GS39783 or CGP44532 selectively decreased nicotine self-administration, whereas coadministration of these compounds had additive effects. BHF177 administration selectively decreased nicotine- but not food-maintained responding under FR5 and progressive ratio schedules. The nicotine-induced enhancement of brain reward function was blocked by BHF177 or CGP44532, although the highest doses of both compounds, particularly CGP44532, decreased brain reward function when administered alone, suggesting an additive, rather than interactive, effect. Overall, the present results indicate that GABA(B) receptor-positive modulators, similarly to GABA(B) receptor agonists, attenuated the reinforcing and reward

  17. Positive Modulation of GABAB Receptors Decreased Nicotine Self-administration and Counteracted Nicotine-induced Enhancement of Brain Reward Function in Rats

    Science.gov (United States)

    Paterson, Neil E.; Vlachou, Styliani; Guery, Sebastien; Kaupmann, Klemens; Froestl, Wolfgang; Markou, Athina

    2008-01-01

    Acute administration of γ-aminobutyric acid (GABA)-B receptor agonists decreases nicotine, cocaine, ethanol, and heroin self-administration, and also decreases food-maintained responding and suppresses locomotor activity at high doses. GABAB receptor positive modulators may represent potentially improved therapeutic compounds because of their fewer side-effects than receptor agonists. The present study investigated the effects of administration of the GABAB receptor positive modulators 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177), and co-administration of the GABAB receptor positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) with the GABAB receptor agonist (3-amino-2[S]-hydroxypropyl)-methylphosphinic acid (CGP44532) on nicotine- and food-maintained responding under fixed-ratio 5 (FR5) and progressive-ratio schedules of reinforcement. Furthermore, the effects of BHF177 and CGP44532 on nicotine-induced enhancement of brain reward function were evaluated. The results indicated that administration of CGP7930 decreased nicotine self-administration under an FR5 schedule. Administration of either GS39783 or CGP44532 selectively decreased nicotine self-administration, while co-administration of these compounds had additive effects. BHF177 administration selectively decreased nicotine-, but not food-, maintained responding under FR5 and progressive-ratio schedules. The nicotine-induced enhancement of brain reward function was blocked by BHF177 or CGP44532, although the highest doses of both compounds, particularly CGP44532, decreased brain reward function when administered alone, suggesting an additive, rather than interactive, effect. Overall, the present results indicate that GABAB receptor positive modulators, similarly to GABAB receptor agonists, attenuated the reinforcing and reward

  18. The Andersen aerobic fitness test

    DEFF Research Database (Denmark)

    Aadland, Eivind; Terum, Torkil; Mamen, Asgeir

    2014-01-01

    BACKGROUND: High aerobic fitness is consistently associated with a favorable metabolic risk profile in children. Direct measurement of peak oxygen consumption (VO2peak) is often not feasible, thus indirect tests such as the Andersen test are required in many settings. The present study seeks...... of agreement) were 26.7±125.2 m for test 2 vs. test 1 (pfit in the present sample; thus, we suggest a new equation: VO2peak = 23....... Researchers should be aware of the amount of noise in indirect tests that estimate aerobic fitness....

  19. In vivo human buccal permeability of nicotine

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  20. Adaptation to nicotine feeding in Myzus persicae.

    Science.gov (United States)

    Ramsey, John S; Elzinga, Dezi A; Sarkar, Pooja; Xin, Yi-Ran; Ghanim, Murad; Jander, Georg

    2014-08-01

    Lineages of the generalist hemipteran herbivore Myzus persicae (green peach aphid) that have expanded their host range to include tobacco often have elevated nicotine tolerance. The tobacco-adapted M. persicae lineage used in this study was able to reproduce on nicotine-containing artificial diets at concentrations that were 15-fold higher than those that were lethal to a non-adapted M. persicae lineage. Fecundity of the nicotine-tolerant M. persicae lineage was increased by 100 μM nicotine in artificial diet, suggesting that this otherwise toxic alkaloid can serve as a feeding stimulant at low concentrations. This lineage also was pre-adapted to growth on tobacco, exhibiting no drop in fecundity when it was moved onto tobacco from a different host plant. Although growth of the non-tobacco-adapted M. persicae lineage improved after three generations on tobacco, this higher reproductive rate was not associated with increased nicotine tolerance. Myzus persicae gene expression microarrays were used to identify transcripts that are up-regulated in response to nicotine in the tobacco-adapted lineage. Induced expression was found for CYP6CY3, which detoxifies nicotine in M. persicae, other genes encoding known classes of detoxifying enzymes, and genes encoding secreted M. persicae salivary proteins.

  1. 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.

  2. AEROBIC EXERCISE IN PULMONARY REHABILITATION

    Directory of Open Access Journals (Sweden)

    Thiago Brasileiro de Vasconcelos

    2013-05-01

    Full Text Available The aim of this study was to conduct a literature review on the usefulness of aerobic exercise in pulmonary rehabilitation. This is an exploratory study of literature through the electronic databases Medline, Lilacs, Scielo, Pubmed and Google Scholar, published between 1996 and 2012, conducted during the period February to May 2012 with the following keywords: COPD, pulmonary rehabilitation, aerobic exercises, physical training, quality of life. The change in pulmonary function and dysfunction of skeletal muscles that result in exercise intolerance and reduced fitness and may cause social isolation, depression, anxiety and addiction. The training exercise is the most important component of the program of pulmonary rehabilitation where the aerobic training provides consistent results in clinical improvement in levels of exercise tolerance and decreased dyspnea generating more benefits to the body, reducing the chance of cardiovascular disease and improves quality and expectation of life. We demonstrated that the use of aerobic exercise in pulmonary rehabilitation program, allows an improvement of motor skills, decreased muscle fatigue and deconditioning, reducing sedentary lifestyle; however, has little or no effect on the reduction of strength and atrophy muscle.

  3. Aerobic exercise in pulmonary rehabilitation

    Directory of Open Access Journals (Sweden)

    Thiago Brasileiro de Vasconcelos

    2013-01-01

    Full Text Available The aim of this study was to conduct a literature review on the usefulness of aerobic exercise in pulmonary rehabilitation. This is an exploratory study of literature through the electronic databases Medline, Lilacs, Scielo, Pubmed and Google Scholar, published between 1996 and 2012, conducted during the period February to May 2012 with the following keywords: COPD, pulmonary rehabilitation, aerobic exercises, physical training, quality of life. The change in pulmonary function and dysfunction of skeletal muscles that result in exercise intolerance and reduced fitness and may cause social isolation, depression, anxiety and addiction. The training exercise is the most important component of the program of pulmonary rehabilitation where the aerobic training provides consistent results in clinical improvement in levels of exercise tolerance and decreased dyspnea generating more benefits to the body, reducing the chance of cardiovascular disease and improves quality and expectation of life. We demonstrated that the use of aerobic exercise in pulmonary rehabilitation program, allows an improvement of motor skills, decreased muscle fatigue and deconditioning, reducing sedentary lifestyle; however, has little or no effect on the reduction of strength and atrophy muscle.

  4. 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.

  5. Nicotine Alters the Gut Microbiome and Metabolites of Gut-Brain Interactions in a Sex-Specific Manner.

    Science.gov (United States)

    Chi, Liang; Mahbub, Ridwan; Gao, Bei; Bian, Xiaoming; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

    2017-12-18

    As the primary active substance in tobacco, nicotine affects the activity of the central nervous system, and its effects are sex-dependent. There are complex interactions between the gut and brain, and the gut microbiome can influence neuronal activity and host behavior, with diverse chemical signaling being involved. However, it is unclear whether nicotine can affect the normal gut microbiome and associated chemical signaling of the gut-brain axis. Sex is an important factor that shapes the gut microbiome, but the role of sex in the interaction among nicotine, gut bacteria, and related metabolites remains unknown. In this study, we applied high-throughput sequencing and gas chromatography-mass spectrometry (GC-MS) to explore how nicotine exposure affects the gut microbiome and its metabolism in female and male C57BL/6J mice, with a focus on the chemical signaling involved in gut-brain interactions. 16S sequencing results indicated that the community composition of the gut microbiome was differentially perturbed by nicotine in females and males. Differential alterations of bacterial carbohydrate metabolic pathways are consistent with lower body weight gain in nicotine-treated males. Oxidative stress response and DNA repair genes were also specifically enriched in the nicotine-treated male gut microbiome. The fecal metabolome indicated that multiple neurotransmitters, such as glutamate, gamma-aminobutyric acid (GABA), and glycine, were differentially altered in female and male mice. Some neuroactive metabolites, including leucine and uric acid, were also changed. This study demonstrates a sex-dependent effect of nicotine on gut microbiome community composition, functional bacterial genes, and the fecal metabolome.

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

    Science.gov (United States)

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

    2018-02-10

    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.

  7. On the deposition of volatiles and semivolatiles from cigarette smoke aerosols: relative rates of transfer of nicotine and ammonia from particles to the gas phase.

    Science.gov (United States)

    Seeman, Jeffrey I; Lipowicz, Peter J; Piadé, Jean-Jacques; Poget, Laurent; Sanders, Edward B; Snyder, James P; Trowbridge, Clarence G

    2004-08-01

    The hypothesis that elevated levels of ammonia-releasing compounds in tobacco and ammonia in mainstream (MS) smoke increase the rate and amount of nicotine evaporation from the particles of MS smoke aerosol was examined by kinetic modeling and experiments with MS cigarette smoke. Computational simulation of a kinetic mechanism describing volatile loss of nicotine, ammonia, and acetic acid from an aqueous solution was used to compute the time-dependent concentration of all species in the model. Because of the high volatility of ammonia relative to that of nicotine, variation over a wide range of initial ammonia concentration had no significant effect upon the rate of loss of nicotine from the model system. The effects of a variation in the volatile loss rate constant for ammonia and for the acid were examined. The simulations show that ammonia is lost from the model solution at a greater rate than nicotine and acid, and the loss of volatile acid has a significant role in the rate and amount of nicotine loss. Simulations with a model system undergoing a continuous steady addition of ammonia showed that high rates of ammonia addition could significantly increase the rate of nicotine volatile loss from the model solution. A series of smoking experiments was performed using blended cigarettes connected to a denuder tube. Deposition of smoke constituents can occur directly from the gas phase and by the deposition of smoke aerosol particles themselves. As nicotine exists >99% in the particle phase of MS smoke, in the absence of particle deposition, denuder tube deposition of nicotine occurs via the evaporation-deposition pathway. Solanesol, a nonvolatile tobacco and smoke terpene, was used to quantify the amount of particle deposition onto the denuder tube. The amount of ammonia deposited on the denuder tube was an order of magnitude greater than that of nicotine, showing that ammonia evaporates from the MS smoke particles much faster than does nicotine. The experimental

  8. Nicotinic activation of laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Ishibashi, Masaru; Leonard, Christopher S; Kohlmeier, Kristi A

    2009-01-01

    Identifying the neurological mechanisms underlying nicotine reinforcement is a healthcare imperative, if society is to effectively combat tobacco addiction. The majority of studies of the neurobiology of addiction have focused on dopamine (DA)-containing neurons of the ventral tegmental area (VTA......). However, recent data suggest that neurons of the laterodorsal tegmental (LDT) nucleus, which sends cholinergic, GABAergic, and glutamatergic-containing projections to DA-containing neurons of the VTA, are critical to gating normal functioning of this nucleus. The actions of nicotine on LDT neurons...... are unknown. We addressed this issue by examining the effects of nicotine on identified cholinergic and non-cholinergic LDT neurons using whole-cell patch clamp and Ca(2+)-imaging methods in brain slices from mice (P12-P45). Nicotine applied by puffer pipette or bath superfusion elicited membrane...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  10. U.S. adults' addiction and harm beliefs about nicotine and low nicotine cigarettes☆

    Science.gov (United States)

    O'Brien, Erin Keely; Nguyen, Anh B.; Persoskie, Alexander; Hoffman, Allison C.

    2017-01-01

    This research described U.S. adults' beliefs about nicotine and low nicotine cigarettes (LNCs) using the nationally-representative Health Information National Trends Survey (HINTS-FDA 2015; N = 3738). About three quarters of people either were unsure of the relationship between nicotine and cancer or incorrectly believed that nicotine causes cancer. People who were non-White, less educated, age 65+, and never established smokers were most likely to be unaware that nicotine is not a cause of cancer. More than a quarter of people held the potentially inaccurate beliefs that LNCs would be less harmful and addictive than typical cigarettes. Whites were more likely than Blacks to believe LNCs were less harmful than typical cigarettes, and never smokers were more likely to believe this than established quitters. Whites and people with at least a college degree were more likely to believe that LNCs would be less addictive than typical cigarettes. Overall, we found that many people, particularly the demographic subgroups identified here, held incorrect beliefs about nicotine and potentially inaccurate beliefs about LNCs. Findings should be considered in assessing the public health impact of marketing low nicotine products. Incorrectly believing that nicotine causes cancer could discourage smokers from switching to safer nicotine-containing alternatives, and could lead nonsmokers to experiment with low nicotine tobacco products, believing that cancer risk would be reduced. Findings underscore the need to educate the public on the health effects of nicotine and LNCs, and can help public health practitioners determine which subgroups should be prioritized in targeted educational efforts. PMID:28034733

  11. U.S. adults' addiction and harm beliefs about nicotine and low nicotine cigarettes.

    Science.gov (United States)

    O'Brien, Erin Keely; Nguyen, Anh B; Persoskie, Alexander; Hoffman, Allison C

    2017-03-01

    This research described U.S. adults' beliefs about nicotine and low nicotine cigarettes (LNCs) using the nationally-representative Health Information National Trends Survey (HINTS-FDA 2015; N=3738). About three quarters of people either were unsure of the relationship between nicotine and cancer or incorrectly believed that nicotine causes cancer. People who were non-White, less educated, age 65+, and never established smokers were most likely to be unaware that nicotine is not a cause of cancer. More than a quarter of people held the potentially inaccurate beliefs that LNCs would be less harmful and addictive than typical cigarettes. Whites were more likely than Blacks to believe LNCs were less harmful than typical cigarettes, and never smokers were more likely to believe this than established quitters. Whites and people with at least a college degree were more likely to believe that LNCs would be less addictive than typical cigarettes. Overall, we found that many people, particularly the demographic subgroups identified here, held incorrect beliefs about nicotine and potentially inaccurate beliefs about LNCs. Findings should be considered in assessing the public health impact of marketing low nicotine products. Incorrectly believing that nicotine causes cancer could discourage smokers from switching to safer nicotine-containing alternatives, and could lead nonsmokers to experiment with low nicotine tobacco products, believing that cancer risk would be reduced. Findings underscore the need to educate the public on the health effects of nicotine and LNCs, and can help public health practitioners determine which subgroups should be prioritized in targeted educational efforts. Published by Elsevier Inc.

  12. Aerobic Biodegradation Characteristic of Different Water-Soluble Azo Dyes

    OpenAIRE

    Shixiong Sheng; Bo Liu; Xiangyu Hou; Bing Wu; Fang Yao; Xinchun Ding; Lin Huang

    2017-01-01

    This study investigated the biodegradation performance and characteristics of Sudan I and Acid Orange 7 (AO7) to improve the biological dye removal efficiency in wastewater and optimize the treatment process. The dyes with different water-solubility and similar molecular structure were biologically treated under aerobic condition in parallel continuous-flow mixed stirred reactors. The biophase analysis using microscopic examination suggested that the removal process of the two azo dyes is dif...

  13. Effects of Chronic Buspirone Treatment on Nicotine and Concurrent Nicotine+Cocaine Self-Administration

    Science.gov (United States)

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J

    2013-01-01

    Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal pharmacotherapy would reduce both cigarette smoking and cocaine abuse. Buspirone (Buspar) is a clinically available, non-benzodiazepine anxiolytic medication that acts on serotonin and dopamine systems. In preclinical studies, it reduced cocaine self-administration following both acute and chronic treatment in rhesus monkeys. The present study evaluated the effectiveness of chronic buspirone treatment on self-administration of intravenous (IV) nicotine and IV nicotine+cocaine combinations. Five cocaine-experienced adult rhesus monkeys (Macaca mulatta) were trained to self-administer nicotine or nicotine+cocaine combinations, and food pellets (1 g) during four 1-h daily sessions under a second-order schedule of reinforcement (FR 2 (VR16:S)). Each nicotine+cocaine combination maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (Pnicotine alone (0.001–0.1 mg/kg/inj; Pnicotine (0.001 or 0.0032 mg/kg/inj)+cocaine combinations (0.0032 mg/kg/inj; Pnicotine alone and nicotine+cocaine polydrug combinations in a nonhuman primate model of drug self-administration. PMID:23337868

  14. Opname van nicotine door kippen en overdracht naar eieren bij toepassing van nicotine tegen bloedluis

    NARCIS (Netherlands)

    Traag, W.A.; Rijk, de T.C.; Zomer, P.; Vos Van Avezathe, A.; Kan, C.A.; Zeilmaker, M.; Hoogenboom, L.A.P.

    2005-01-01

    Uit onderzoek van de AID blijkt nicotine gebruikt te worden voor de bestrijding van bloedluis bij kippen. Dit levert mogelijk gezondheidsrisico's op voor de consument van het kippenvlees of de eieren. Omdat niet duidelijk is of het nicotine na de bestrijding van bloedluis in het vlees of eieren

  15. 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...

  16. 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...

  17. 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

  18. 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

  19. The effect of an acute nicotine infusion on the local cerebral glucose utilization of the awake rat.

    Science.gov (United States)

    Grünwald, F; Schröck, H; Kuschinsky, W

    1988-01-01

    The effect of acute infusion of nicotine on local cerebral glucose utilization (LCGU) was studied in discrete regions of the central nervous system of the rat by means of the quantitative autoradiographic (14C)2-deoxy-D-glucose method described by Sokoloff et al. Nicotine was administered in three dosages: 0.5 microgram/kg/min, 1.58 micrograms/kg/min, and 5 micrograms/kg/min. The resulting plasma concentrations of nicotine were 10/39/114 ng/ml plasma. During the experiment blood pressure, heart rate, body temperature, hematocrit, acid-base status, and plasma glucose concentration showed no or minor changes. Nicotine significantly increased LCGU in a dose-dependent manner in the following 9 of 45 examined structures: substantia nigra (compact part), superior colliculus (superficial grey layer), interpeduncular nucleus and cingulate cortex (P less than 0.01); lateral geniculate body, optic chiasm, anteroventral and anteromedial nucleus of thalamus and mamillary body (P less than 0.05). For most of these structures with increased LCGU, other investigators have reported a high regional receptor binding of nicotine (exception: mamillary body and optic chiasm). It is concluded that nicotine has distinct effects on the functional activity of localized brain areas.

  20. Positive Modulation of GABAB Receptors Decreased Nicotine Self-administration and Counteracted Nicotine-induced Enhancement of Brain Reward Function in Rats

    OpenAIRE

    Paterson, Neil E.; Vlachou, Styliani; Guery, Sebastien; Kaupmann, Klemens; Froestl, Wolfgang; Markou, Athina

    2008-01-01

    Acute administration of γ-aminobutyric acid (GABA)-B receptor agonists decreases nicotine, cocaine, ethanol, and heroin self-administration, and also decreases food-maintained responding and suppresses locomotor activity at high doses. GABAB receptor positive modulators may represent potentially improved therapeutic compounds because of their fewer side-effects than receptor agonists. The present study investigated the effects of administration of the GABAB receptor positive modulators 2,6-Di...

  1. Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits.

    Science.gov (United States)

    Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M; Smith, Misty D; Hanson, Glen R; Fleckenstein, Annette E

    2015-07-11

    Previous studies have demonstrated that methamphetamine abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors. The present study investigated whether nicotine attenuates methamphetamine-induced novel object recognition deficits in rats and explored potential underlying mechanisms. Adolescent or adult male Sprague-Dawley rats received either nicotine water (10-75 μg/mL) or tap water for several weeks. Methamphetamine (4 × 7.5mg/kg/injection) or saline was administered either before or after chronic nicotine exposure. Novel object recognition was evaluated 6 days after methamphetamine or saline. Serotonin transporter function and density and α4β2 nicotinic acetylcholine receptor density were assessed on the following day. Chronic nicotine intake via drinking water beginning during either adolescence or adulthood attenuated the novel object recognition deficits caused by a high-dose methamphetamine administration. Similarly, nicotine attenuated methamphetamine-induced deficits in novel object recognition when administered after methamphetamine treatment. However, nicotine did not attenuate the serotonergic deficits caused by methamphetamine in adults. Conversely, nicotine attenuated methamphetamine-induced deficits in α4β2 nicotinic acetylcholine receptor density in the hippocampal CA1 region. Furthermore, nicotine increased α4β2 nicotinic acetylcholine receptor density in the hippocampal CA3, dentate gyrus and perirhinal cortex in both saline- and methamphetamine-treated rats. Overall, these findings suggest that nicotine-induced increases in α4β2 nicotinic acetylcholine receptors in the hippocampus and perirhinal cortex might be one mechanism by which novel object recognition deficits are

  2. Donepezil, an acetylcholinesterase inhibitor, attenuates nicotine self-administration and reinstatement of nicotine seeking in rats

    Science.gov (United States)

    Kimmey, Blake A.; Rupprecht, Laura E.; Hayes, Matthew R.; Schmidt, Heath D.

    2013-01-01

    Nicotine craving and cognitive impairments represent core symptoms of nicotine withdrawal and predict relapse in abstinent smokers. Current smoking cessation pharmacotherapies have limited efficacy in preventing relapse and maintaining abstinence during withdrawal. Donepezil is an acetylcholinesterase inhibitor that has been shown previously to improve cognition in healthy non–treatment-seeking smokers. However, there are no studies examining the effects of donepezil on nicotine self-administration and/or the reinstatement of nicotine-seeking behavior in rodents. The present experiments were designed to determine the effects of acute donepezil administration on nicotine taking and the reinstatement of nicotine-seeking behavior, an animal model of relapse in abstinent human smokers. Moreover, the effects of acute donepezil administration on sucrose self-administration and sucrose seeking were also investigated in order to determine whether donepezil's effects generalized to other reinforced behaviors. Acute donepezil administration (1.0 or 3.0 mg/kg, i.p.) attenuated nicotine, but not sucrose self-administration maintained on a fixed-ratio 5 schedule of reinforcement. Donepezil administration also dose-dependently attenuated the reinstatement of both nicotine- and sucrose-seeking behaviors. Commonly reported adverse effects of donepezil treatment in humans are nausea and vomiting. However, at doses required to attenuate nicotine self-administration in rodents, no effects of donepezil on nausea/malaise as measured by pica were observed. Collectively, these results indicate that increased extracellular acetylcholine levels are sufficient to attenuate nicotine taking and seeking in rats and that these effects are not due to adverse malaise symptoms such as nausea. PMID:23231479

  3. Nicotine deprivation attenuates panic reactivity in smokers: Findings from a placebo-controlled nicotine patch study.

    Science.gov (United States)

    Abrams, Kenneth; Krimmel, Sam; Johnson, Stacey; Cieslowski, Kate; Strnad, Helen; Melum, Arielle; Kryder, Caroline

    2017-11-01

    Prospective studies consistently find that smoking is a risk factor for the development of panic disorder (PD). A possible explanation is that nicotine deprivation promotes heightened sensitivity to bodily sensations and/or arterial carbon dioxide (CO 2 ). Abrams et al. (2011) previously found that, in response to a CO 2 rebreathing challenge, smokers experiencing more (vs. less) intense nicotine withdrawal had more severe panic symptoms and a stronger urge to escape. However, participants were aware of the last time they smoked, leaving unclear the extent to which fear reactivity was influenced by the pharmacologic effects of nicotine deprivation versus beliefs regarding when nicotine was most recently used. The present study aimed to ascertain whether nicotine deprivation, independent of beliefs regarding recent nicotine use, promotes fear reactivity among smokers. Moderate to heavy smokers without PD (N = 25) participated in a placebo-controlled, double-blind study consisting of two sessions spaced 1 week apart. Participants abstained from nicotine for 2 hr prior to sessions. During one session participants were given a 21 mg nicotine replacement patch and, during the other, a placebo patch, with the order counterbalanced. For both sessions, after a 3-hr absorption period, participants underwent a 10-min CO 2 rebreathing challenge. Wearing a nicotine (vs. placebo) patch increased self-reported panic reactivity among participants, but did not significantly affect physiological and behavioral measures of reactivity. In smokers without a history of PD, nicotine deprivation attenuates subjective panic reactivity. Possible explanations for the contrast between theory and laboratory findings as well as clinical implications are discussed. © 2017 Wiley Periodicals, Inc.

  4. Effects of tiagabine in combination with intravenous nicotine in overnight abstinent smokers.

    Science.gov (United States)

    Sofuoglu, Mehmet; Mouratidis, Maria; Yoo, Sonah; Culligan, Kerry; Kosten, Thomas

    2005-09-01

    Preclinical studies suggest that medications enhancing the brain gamma amino butyric acid (GABA) system attenuate the rewarding effects of stimulants including nicotine. These preclinical studies have not been followed up in systematic human studies. This study was conducted to examine the effects of a GABAergic medication, tiagabine, on acute physiological and subjective effects of intravenous (i.v.) nicotine and on tobacco withdrawal symptoms in overnight abstinent smokers. The proposed mechanism of action for tiagabine is selective inhibition of GABA transporter type I, which leads to increases in synaptic GABA levels. Eight male and four female smokers participated in a double-blind, placebo-controlled, crossover study. In each of three experimental sessions, participants were treated orally with a single 4- or 8-mg dose of tiagabine or placebo. Two hours following the medication treatment, participants received i.v. saline, followed 30 min later by 1.5 mg/70 kg i.v. nicotine. Tiagabine treatment did not affect the heart rate or blood pressure changes induced by nicotine. There was a significant treatment effect for the subjective responses to nicotine, such that tiagabine, compared to placebo, attenuated the ratings of "good effects" and "drug liking." Tiagabine treatment at 8 mg attenuated the craving for cigarettes and enhanced the cognitive performance in the Classical Stoop Tests, compared to placebo or 4 mg tiagabine condition. These results suggest that GABA enhancing medication tiagabine may reduce the rewarding effects of nicotine and improve cognitive performance in abstinent smokers. The utility of GABA medications for smoking cessation needs to be examined further in controlled clinical trials.

  5. Proteomic and metabolomic analysis reveals rapid and extensive nicotine detoxification ability in honey bee larvae.

    Science.gov (United States)

    du Rand, Esther E; Human, Hannelie; Smit, Salome; Beukes, Mervyn; Apostolides, Zeno; Nicolson, Susan W; Pirk, Christian W W

    2017-03-01

    Despite potential links between pesticides and bee declines, toxicology information on honey bee larvae (Apis mellifera) is scarce and detoxification mechanisms in this development stage are virtually unknown. Larvae are exposed to natural and synthetic toxins present in pollen and nectar through consumption of brood food. Due to the characteristic intensive brood care displayed by honey bees, which includes progressive feeding throughout larval development, it is generally assumed that larvae rely on adults to detoxify for them and exhibit a diminished detoxification ability. We found the opposite. We examined the proteomic and metabolomic responses of in vitro reared larvae fed nicotine (an alkaloid found in nectar and pollen) to understand how larvae cope on a metabolic level with dietary toxins. Larvae were able to effectively detoxify nicotine through an inducible detoxification mechanism. A coordinated stress response complemented the detoxification processes, and we detected significant enrichment of proteins functioning in energy and carbohydrate metabolism, as well as in development pathways, suggesting that nicotine may promote larval growth. Further exploration of the metabolic fate of nicotine using targeted mass spectrometry analysis demonstrated that, as in adult bees, formation of 4-hydroxy-4-(3-pyridyl) butanoic acid, the result of 2'C-oxidation of nicotine, is quantitatively the most significant pathway of nicotine metabolism. We provide conclusive evidence that larvae are capable of effectively catabolising a dietary toxin, suggesting that increased larval sensitivity to specific toxins is not due to diminished detoxification abilities. These findings broaden the current understanding of detoxification biochemistry at different organizational levels in the colony, bringing us closer to understanding the capacity of the colony as a superorganism to tolerate and resist toxic compounds, including pesticides, in the environment. Copyright © 2017

  6. Studies on the nicotine exposure of individual smokers. I. Changes in mouth-level exposure to nicotine on switching to lower nicotine cigarettes.

    Science.gov (United States)

    Forbes, W F; Robinson, J C; Hanley, J A; Colburn, H N

    1976-01-01

    Twenty-four subjects smoked two brands of filter-tipped cigarettes delivering different amounts of nicotine, on the following 4-week schedule: 1. Smoking their usual brand for 1 week. 2. Smoking another brand similar in size, but delivering less nicotine, for 2 weeks. 3. Reverting to their usual brand for 1 week. The amount of nicotine entering the mouth, defined as the mouth-level exposure, was estimated from a determination of the amount of nicotine trapped in the filter of each cigarette smoked. The results indicate a substantial variation in mouth-level exposure for the subjects studied, even among smokers of cigarettes that deliver similar amounts of nicotine when smoked on a machine under standard conditions. For the majority of subjects, however, changing to a lower nicotine cigarette reduced the total daily mouth-level exposure to nicotine and, therefore, presumably the total tar intake.

  7. Design, formulation and evaluation of nicotine chewing gum

    Directory of Open Access Journals (Sweden)

    Abolfazl Aslani

    2012-01-01

    Conclusion: Taste enhancement of nicotine gums was achieved where formulations comprised aspartame as the sweetener and cherry and eucalyptus as the flavoring agents. Nicotine gums of pleasant taste may, therefore, be used as NRT to assist smokers quit smoking.

  8. 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

  9. Smoking cigarettes of low nicotine yield does not reduce nicotine intake as expected: a study of nicotine dependency in Japanese males

    Directory of Open Access Journals (Sweden)

    Ozasa Kotaro

    2004-07-01

    Full Text Available Abstract Background Many Japanese believe that low-yield cigarettes are less hazardous than regular cigarettes, and many smokers consume low-yield cigarettes to reduce their risks from smoking. We evaluate the association between actual nicotine intake and brand nicotine yield, and the influence of nicotine dependence on this association. Methods The study subjects included 458 Japanese male smokers, aged 51.2 ± 9.9 years, who participated in health check-ups in a hospital in 1998 and 2000. Each subject filled out a self-administered smoking questionnaire and the score of each on the Fagerström Test for Nicotine Dependence was calculated. Urinary cotinine concentration was measured at the time of participation. Results The geometric mean of urinary cotinine concentration was 535 ng/mgCr for those who smoked brands with the lowest nicotine (0.1 mg on the package, compared with 1010 ng/mgCr for those who smoked brands with the highest (0.9–2.4 mg, weighted mean of 1.1 mg. Thus, despite the 11-fold ratio of nicotine yield on the packages, the ratio of urinary cotinine level was less than twofold. Both nicotine yield on the package and nicotine dependence significantly increased urinary cotinine concentration, and the negative interaction between them almost attained statistical significance. Cotinine concentration in heavily dependent smokers was consistently high regardless of the nicotine yield of brands. Conclusions The nicotine yield of cigarettes measured by machine-smoking does not reliably predict the exposure of smokers. Smokers consuming low-yield nicotine cigarettes did not reduce actual intake of nicotine to the level that might be expected, especially for those heavily dependent on nicotine. Current labeling practices are misleading for the two-third of smokers who are moderately or highly dependent on nicotine.

  10. Tobacco and Nicotine Product Testing

    Science.gov (United States)

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

    2012-01-01

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

  11. Nicotine administration and withdrawal affect survival in systemic inflammation models

    OpenAIRE

    Steiner, Alexandre A.; Oliveira, Daniela L.; Roberts, Jennifer L.; Petersen, Scott R.; Romanovsky, Andrej A.

    2008-01-01

    How different regimens of nicotine administration and withdrawal affect systemic inflammation is largely unknown. We studied the effects of chronic and acute nicotine administration and of nicotine withdrawal on the outcome of aseptic and septic systemic inflammation. Male C57BL/6 mice were implanted with subcutaneous osmotic pumps (to deliver nicotine) and intrabrain telemetry probes (to measure temperature). Aseptic inflammation was induced by lipopolysaccharide (40 mg/kg ip); sepsis was in...

  12. 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.

  13. Acute aerobic exercise modulates primary motor cortex inhibition.

    Science.gov (United States)

    Mooney, Ronan A; Coxon, James P; Cirillo, John; Glenny, Helen; Gant, Nicholas; Byblow, Winston D

    2016-12-01

    Aerobic exercise can enhance neuroplasticity although presently the neural mechanisms underpinning these benefits remain unclear. One possible mechanism is through effects on primary motor cortex (M1) function via down-regulation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The aim of the present study was to examine how corticomotor excitability (CME) and M1 intracortical inhibition are modulated in response to a single bout of moderate intensity aerobic exercise. Ten healthy right-handed adults were participants. Single- and paired-pulse transcranial magnetic stimulation was applied over left M1 to obtain motor-evoked potentials in the right flexor pollicis brevis. We examined CME, cortical silent period (SP) duration, short- and long-interval intracortical inhibition (SICI, LICI), and late cortical disinhibition (LCD), before and after acute aerobic exercise (exercise session) or an equivalent duration without exercise (control session). Aerobic exercise was performed on a cycle ergometer for 30 min at a workload equivalent to 60 % of maximal cardiorespiratory fitness (VO 2 peak; heart rate reserve = 75 ± 3 %, perceived exertion = 13.5 ± 0.7). LICI was reduced at 10 (52 ± 17 %, P = 0.03) and 20 min (27 ± 8 %, P = 0.03) post-exercise compared to baseline (13 ± 4 %). No significant changes in CME, SP duration, SICI or LCD were observed. The present study shows that GABA B -mediated intracortical inhibition may be down-regulated after acute aerobic exercise. The potential effects this may have on M1 plasticity remain to be determined.

  14. Comparative aerobic soil metabolism of fenvalerate isomers

    International Nuclear Information System (INIS)

    Lee, P.W.; Powell, W.R.; Stearns, S.M.; McConnell, O.J.

    1987-01-01

    An aerobic soil metabolism study was conducted to determine the degradation rate of individual isomer of fenvalerate and to assess the potential influence of the RS, SR, and RR isomers to the metabolism of the most insecticidally active SS isomer. Individual [phenoxyphenyl- 14 C]fenvalerate isomers degraded at different rates. The calculated half-lives for the SR, RS, SS, and RR isomers in fenvalerate (racemic mixture) were 155, 89, 108, and 178 days, respectively. The resolved SS isomer degraded at a faster rate with a calculated half-life of 74 days. Racemization of the resolved SS isomer did not occur. A qualitative difference in the chemical nature of soil metabolites between fenvalerate and the resolved SS isomer was not observed. Soil degradation products, phenoxybenzoic acid, 3-(4-hydroxyphenoxy)benzoic acid, and 4'-OH- and CONH 2 -fenvalerate, each accounted for less than 2% of the applied radioactivity. Extensive degradation of these soil metabolites was evident since approximately 50% of the applied radioactivity was recovered as 14 C 2 and as unextractable bound residues

  15. Reduced nicotine exposure and abstinence outcome in two nicotine fading methods.

    Science.gov (United States)

    McGovern, P G; Lando, H A

    1991-01-01

    Two methods of nicotine fading as a smoking cessation preparation technique were compared. A brand-switching procedure and a three-stage set of "Nicotine Faders" graduated filters were the preparation strategies. Both methods implemented a putative 30-50-80% nicotine exposure reduction schedule in three weekly phases. There were a total of 110 study participants (57 in brand switching) enrolled in eight clinic groups. Results indicated that at the 80% reduction level, meaningful reductions in nicotine (measured by its metabolite cotinine) and carbon monoxide (CO) exposure were measurable with both nicotine fading procedures. Overall pooled nicotine and CO exposure drops from baselines of 48.2% and 35.5%, respectively, were recorded. The abstinence outcome measures (pooled 1-year abstinence prevalence = 30.9%) were not significantly different between the two preparation strategies. Trends in nicotine and CO exposure drops, and abstinence outcome measures, however, were consistently in favor of the graduated filters. Potential advantages of filters in the context of a preparation-for-quitting strategy were suggested.

  16. Effect of aerobic exercise on the atherogenic index of plasma in middle-aged Chinese men with various body weights.

    Science.gov (United States)

    Shen, Shiwei; Lu, Yun; Dang, Yingjie; Qi, Huajin; Shen, Zhenhai; Wu, Liuxin; Li, Feng; Yang, Chengjian; Qiang, Dongchang; Yang, Yan; Shui, Kedong; Bao, Yanying

    2017-03-01

    The aim of this study was to examine the correlation between aerobic exercise and the atherogenic index of plasma (AIP) in middle-aged Chinese men stratified by body weight. A cross-sectional study, which recruited 26,701 middle-aged Chinese men undergoing health examinations in our hospital from 1st January 2014 to 30th June 2015 was performed, and the associations between body weight and AIP, and aerobic exercise and AIP were evaluated. The mean AIP levels were -0.016±0.305, 0.138±0.3171 and 0.211±0.3243 in normal weight, overweight and obese subjects, respectively, and appeared to rise with body weight. Significantly higher AIP levels were observed in subjects with a weekly aerobic exercise period ≥90min than in those with a weekly aerobic exercise period aerobic exercise period ≥90min and aerobic exercise significantly reduced AIP after adjustment for age, systolic blood pressure, diastolic blood pressure, body mass index (BMI), fasting blood glucose and uric acid. Lowering body weight and/or increasing aerobic exercise time may reduce AIP, and lowering body weight results in a greater reduction in AIP than aerobic exercise. Weight control combined with increased aerobic exercise time may cause a synergistic effect on the reduction of AIP. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Lower limb loading in step aerobic dance.

    Science.gov (United States)

    Wu, H-W; Hsieh, H-M; Chang, Y-W; Wang, L-H

    2012-11-01

    Participation in aerobic dance is associated with a number of lower extremity injuries, and abnormal joint loading seems to be a factor in these. However, information on joint loading is limited. The purpose of this study was to investigate the kinetics of the lower extremity in step aerobic dance and to compare the differences of high-impact and low-impact step aerobic dance in 4 aerobic movements (mambo, kick, L step and leg curl). 18 subjects were recruited for this study. High-impact aerobic dance requires a significantly greater range of motion, joint force and joint moment than low-impact step aerobic dance. The peak joint forces and moments in high-impact step aerobic dance were found to be 1.4 times higher than in low-impact step aerobic dance. Understanding the nature of joint loading may help choreographers develop dance combinations that are less injury-prone. Furthermore, increased knowledge about joint loading may be helpful in lowering the risk of injuries in aerobic dance instructors and students. © Georg Thieme Verlag KG Stuttgart · New York.

  18. 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

  19. [An autopsy case of fatal nicotine poisoning].

    Science.gov (United States)

    Takayasu, T; Ohshima, T; Lin, Z; Nishigami, J; Nakaya, T; Maeda, H; Tanaka, N

    1992-10-01

    A fatal case of nicotine poisoning is reported in which a 44-year-old female committed suicide in a short time by taking orally the eluate from tobacco. External examination showed no abnormal findings except for markedly dark red-purple postmortem lividity, and internal examination demonstrated no pathological changes but the signs of sudden death. Through the toxicological investigation by GC and GC-MS, however, nicotine was detected in the solution which she had taken orally and in the blood, urine and the contents of the stomach and small intestine. The nicotine concentrations of the blood, urine and contents of stomach and small intestine were 6.3 micrograms/ml, 1.5 micrograms/ml, 30 micrograms/ml and 71 micrograms/g respectively, and enough to be lethal.

  20. Hormones, Nicotine and Cocaine: Clinical Studies

    Science.gov (United States)

    Mello, Nancy K.

    2009-01-01

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

  1. Catalytic aerobic oxidation of bio-renewable chemicals

    DEFF Research Database (Denmark)

    Gorbanev, Yury

    , EDS, XRF and other methods. Supported gold and ruthenium hydroxide catalyst systems were explored for the aerobic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDA), a potential polymer building block for the plastic industry, or its dimethyl ester (FDMC). High product...... selectivities and yields were obtained under optimized conditions. Heterogeneous catalysts consisting of Au nanoparticles on different supports were shown to efficiently oxidize HMF to FDA or FDMC in water or methanol, respectively. Additionally, the reaction conditions were shown to be adjustable...... with supported Ru(OH)x catalysts in organic solvents. The examined catalyst systems and reaction conditions were also shown to be applicable for the efficient oxidation of other substituted furans. Furthermore, novel catalytic systems comprising vanadia supported on zeolites were investigated for the aerobic...

  2. Nicotine metabolism and addiction among adolescent smokers.

    Science.gov (United States)

    Rubinstein, Mark L; Shiffman, Saul; Moscicki, Anna-Barbara; Rait, Michelle A; Sen, Saunak; Benowitz, Neal L

    2013-02-01

    The purpose of this study was to determine the association between the nicotine metabolic rate and smoking behavior, including addiction, in adolescent smokers. Baseline data from a prospective study of adolescent smoking behaviors and nicotine metabolism. The setting was an out-patient university hospital in San Francisco. Adolescent smokers (n = 164) aged 13-17 years old. Participants completed self-report measures of smoking behavior and nicotine dependence (modified Fagerström Tolerance Questionnaire: mFTQ). The nicotine metabolite ratio (NMR), a phenotypic marker of the rate of nicotine metabolism, was calculated using the ratio of concentrations of deuterium-labeled 3'-hydroxycotinine to cotinine-d(4) . Participants reported smoking a mean of 2.86 cigarettes per day (CPD) [median = 1.78, standard deviation (SD) = 3.35] for 1.37 years (median = 1.0, SD = 1.36). Results from multivariate analyses accounting for age, race/ethnicity, gender and duration of smoking indicated that slower metabolizers smoked more CPD than faster metabolizers (the NMR was inversely related to CPD; P = 0.02). Slower metabolizers also showed greater dependence on the mFTQ (NMR was negatively associated with the mFTQ; P = 0.02). In adolescence, slower clearance of nicotine may be associated with greater levels of addiction, perhaps mediated by a greater number of cigarettes smoked. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  3. 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...

  4. Quality of life after quitting smoking and initiating aerobic exercise.

    Science.gov (United States)

    Bloom, Erika Litvin; Minami, Haruka; Brown, Richard A; Strong, David R; Riebe, Deborah; Abrantes, Ana M

    2017-10-01

    Quitting smoking and aerobic exercise each improve health. Although smokers may be concerned that quitting smoking will reduce their quality of life (QOL), recent research has shown that cessation is associated with QOL benefits. Elements of smoking cessation interventions, such as exercise, may contribute to changes in QOL. However, it is unknown whether initiating exercise in the context of smoking cessation is associated with greater or different effects on QOL than smoking cessation alone. The current study is a secondary analysis of data from a randomized trial (n = 61) of an exercise intervention for smoking cessation. We hypothesized that smoking abstinence and engagement in exercise would have positive, additive effects on QOL at end-of-treatment, 6- and, 12-month follow-ups. Sedentary adult smokers were randomized to the exercise intervention or a health education control (HEC) group. Additionally, all participants received smoking cessation counseling and nicotine patches. Data were analyzed using actual engagement in exercise, rather than group assignment as a proxy for exercise engagement, because some HEC participants also began exercising. Abstinence was positively associated with higher total and physical health QOL at follow-up. Exercise was not associated with total QOL and only marginally associated with physical health QOL, but was positively related to overall sense of well-being. Emphasizing that smoking cessation is associated with higher QOL may help motivate smokers to initiate quit attempts.

  5. Animal Research on Nicotine Reduction: Current Evidence and Research Gaps.

    Science.gov (United States)

    Smith, Tracy T; Rupprecht, Laura E; Denlinger-Apte, Rachel L; Weeks, Jillian J; Panas, Rachel S; Donny, Eric C; Sved, Alan F

    2017-09-01

    A mandated reduction in the nicotine content of cigarettes may improve public health by reducing the prevalence of smoking. Animal self-administration research is an important complement to clinical research on nicotine reduction. It can fill research gaps that may be difficult to address with clinical research, guide clinical researchers about variables that are likely to be important in their own research, and provide policy makers with converging evidence between clinical and preclinical studies about the potential impact of a nicotine reduction policy. Convergence between clinical and preclinical research is important, given the ease with which clinical trial participants can access nonstudy tobacco products in the current marketplace. Herein, we review contributions of preclinical animal research, with a focus on rodent self-administration, to the science of nicotine reduction. Throughout this review, we highlight areas where clinical and preclinical research converge and areas where the two differ. Preclinical research has provided data on many important topics such as the threshold for nicotine reinforcement, the likelihood of compensation, moderators of the impact of nicotine reduction, the impact of environmental stimuli on nicotine reduction, the impact of nonnicotine cigarette smoke constituents on nicotine reduction, and the impact of nicotine reduction on vulnerable populations. Special attention is paid to current research gaps including the dramatic rise in alternative tobacco products, including electronic nicotine delivery systems (ie, e-cigarettes). The evidence reviewed here will be critical for policy makers as well as clinical researchers interested in nicotine reduction. This review will provide policy makers and clinical researchers interested in nicotine reduction with an overview of the preclinical animal research conducted on nicotine reduction and the regulatory implications of that research. The review also highlights the utility of

  6. Binding, uptake, and release of nicotine by human gingival fibroblasts

    International Nuclear Information System (INIS)

    Hanes, P.J.; Schuster, G.S.; Lubas, S.

    1991-01-01

    Previous studies of the effects of nicotine on fibroblasts have reported an altered morphology and attachment of fibroblasts to substrates and disturbances in protein synthesis and secretion. This altered functional and attachment response may be associated with changes in the cell membrane resulting from binding of the nicotine, or to disturbances in cell metabolism as a result of high intracellular levels of nicotine. The purpose of the present study, therefore, was to (1) determine whether gingival fibroblasts bound nicotine and if any binding observed was specific or non-specific in nature; (2) determine whether gingival fibroblasts internalized nicotine, and if so, at what rate; (3) determine whether gingival fibroblasts also released nicotine back into the extracellular environment; and (4) if gingival fibroblasts release nicotine intact or as a metabolite. Cultures of gingival fibroblasts were prepared from gingival connective tissue biopsies. Binding was evaluated at 4 degree C using a mixture of 3 H-nicotine and unlabeled nicotine. Specific binding was calculated as the difference between 3 H-nicotine bound in the presence and absence of unlabeled nicotine. The cells bound 1.44 (+/- 0.42) pmols/10(6) cells in the presence of unlabeled nicotine and 1.66 (+/- 0.55) pmols/10(6) cells in the absence of unlabeled nicotine. The difference was not significant. Uptake of nicotine was measured at 37 degree C after treating cells with 3 H-nicotine for time periods up to 4 hours. Uptake in pmols/10(6) cells was 4.90 (+/- 0.34) at 15 minutes, 8.30 (+/- 0.75) at 30 minutes, 12.28 (+/- 2.62) at 1 hour and 26.31 (+/- 1.15) at 4 hours

  7. Feeding of tobacco blend or nicotine induced weight loss associated with decreased adipocyte size and increased physical activity in male mice.

    Science.gov (United States)

    Liu, Mingxia; Chuang Key, Chia-Chi; Weckerle, Allison; Boudyguina, Elena; Sawyer, Janet K; Gebre, Abraham K; Spoo, Wayne; Makwana, Om; Parks, John S

    2018-03-01

    Although epidemiological data and results from rodent studies support an inverse relationship between nicotine consumption and body weight, the molecular mechanisms are poorly understood. CD-1 mice were fed a basal diet or a basal diet containing low or high dose smokeless tobacco blend or high dose nicotine tartrate for 14 weeks. High dose tobacco blend and nicotine tartrate diets vs. basal diet reduced mouse body weight (16.3% and 19.7%, respectively), epididymal (67.6% and 72.5%, respectively) and brown adipose weight (42% and 38%, respectively), epididymal adipocyte size (46.4% and 41.4%, respectively), and brown adipose tissue lipid droplet abundance, with no elevation of adipose tissue inflammation. High dose tobacco blend and nicotine diets also increased mouse physical activity and decreased respiratory exchange ratio, suggesting that high dose nicotine intake induces adipose tissue triglyceride lipolysis to provide fatty acids as an energy source. Both low and high dose tobacco blend and nicotine diet feeding vs. basal diet increased plasma insulin levels (2.9, 3.6 and 4.3-fold, respectively) and improved blood glucose disposal without affecting insulin sensitivity. Feeding of the high dose tobacco blend or nicotine feeding in mice induces body weight loss likely by increasing physical activity and stimulating adipose tissue triglyceride lipolysis. Copyright © 2018. Published by Elsevier Ltd.

  8. The α7 nicotinic acetylcholine receptor complex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Mikkelsen, Jens D

    2012-01-01

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

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

    Science.gov (United States)

    de Fiebre, C M; Collins, A C

    1988-01-01

    Male and female long-sleep (LS) and short-sleep (SS) mice were pretreated with a subseizure-producing dose of nicotine (2.0 mg/kg) 7.5, 15 and 30 minutes prior to challenge with seizure-producing doses of this drug. Nicotine pretreated animals were less susceptible to nicotine-induced seizures than were saline pretreated animals. The latency to seizure following nicotine challenge was greater in nicotine pretreated animals than in saline controls. Nicotine pretreated LS mice show a greater decrease in nicotine-induced seizure susceptibility than do nicotine pretreated SS mice. This decrease in seizure susceptibility is consistent with induction of nicotinic receptor desensitization via nicotine pretreatment. It is hypothesized that LS and SS mice might differ in sensitivity to nicotine in part because they differ in baseline levels of desensitized versus functional nicotinic receptors.

  10. Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES.

    Science.gov (United States)

    Weltzin, Maegan M; Huang, Yanzhou; Schulte, Marvin K

    2014-06-05

    A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands. PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5-10mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2+/beta2- interface and is dependent on residue beta2D218. HEPES did not potentiate low-sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES✩

    Science.gov (United States)

    Weltzin, Maegan M; Huang, Yanzhou; Schulte, Marvin K

    2013-01-01

    A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands. PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5–10 mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2+/beta2− interface and is dependent on residue beta2D218. HEPES did not potentiate low-sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors. PMID:22732654

  12. Impact of silage additives on aerobic stability and characteristics of high-moisture maize during exposure to air, and on fermented liquid feed

    DEFF Research Database (Denmark)

    Canibe, Nuria; Kristensen, Niels Bastian; Jensen, Bent Borg

    2014-01-01

    with each of three HMM samples: (i) The HMM as is (CONTROL); and the control added (ii) acids (ACID); (iii) heterofermentative lactic acid bacteria (HETERO); or (iv) homofermentative lactic acid bacteria (HOMO). After ensiling, aerobic stability was measured (Aim 1) and FLF prepared (Aim 2). The ACID...

  13. Chronic nicotine administration improves attention while nicotine withdrawal induces performance deficits in the 5-choice serial reaction time task in rats

    OpenAIRE

    Semenova, Svetlana; Stolerman, Ian P.; Markou, Athina

    2007-01-01

    Nicotine appears to enhance attention, while nicotine withdrawal leads to attentional deficits in humans that are ameliorated with nicotine administration. However, there has been much debate as to whether nicotine improves performance under baseline conditions, or only ameliorates attentional deficits. Thus, we studied the effects of acute and chronic nicotine administration and nicotine withdrawal on attentional performance in the 5-choice serial reaction time task (5-CSRTT) in Wistar and S...

  14. 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.

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

    African Journals Online (AJOL)

    ABSTRACT. Nicotine is a pharmacologically active and addictive alkaloid component of the cigarette smoke, and its effects on male reproductive system and fertility are well documented. Influence of ascorbic acid on reproductive functions of male wistar rats exposed to nicotine was examined in this study. Thirty-two adult ...

  16. Nicotine delivery and pharmacologic response from Verve, an oral nicotine delivery product☆

    Science.gov (United States)

    Koszowski, Bartosz; Viray, Lauren C.; Stanfill, Stephen B.; Lisko, Joseph G.; Rosenberry, Zach R.; Potts, Jennifer L.; Pickworth, Wallace B.

    2016-01-01

    Verve, an oral nicotine delivery product (ONDP), was introduced by Nu Mark (Altria Client Group, Richmond VA) for smokers to use in places where smoking is prohibited. This study assessed the effect of this ONDP on plasma nicotine levels, heart rate, product satisfaction, and ability to suppress smoking urge and cigarette cravings. Thirteen daily cigarette smokers [8 men and 5 women; average age 33.4 years] attended two laboratory sessions, one occurred after overnight tobacco abstinence. Plasma samples were collected before and after ONDP use and measured for nicotine. In non-abstinent smokers, mean plasma nicotine levels increased from 18.3 to 21.0 ng/mL. In abstinent smokers, average nicotine levels increased from 3.1 to 4.5 ng/mL. After overnight tobacco abstinence, ONDP use significantly (p < 0.01) increased heart rate from 69 beats per minute (bpm) to 75 bpm; while urge to smoke decreased significantly (p < 0.01) from a score of 8.6 to 4.9. Participants indicated moderate product satisfaction that was not changed by tobacco abstinence. Analysis of unused ONDP revealed total nicotine levels of 1.68 ± 0.09 mg/disc. Spent ONDP discs were also analyzed to determine % nicotine liberated during chewing; results were 80% in the non-abstinent and 82% in the abstinent conditions (ns). Our study results indicate that ONDP use can increase plasma nicotine levels and heart rate and reduce cigarette cravings in abstinent smokers. PMID:26096037

  17. Nicotine delivery and pharmacologic response from Verve, an oral nicotine delivery product.

    Science.gov (United States)

    Koszowski, Bartosz; Viray, Lauren C; Stanfill, Stephen B; Lisko, Joseph G; Rosenberry, Zach R; Potts, Jennifer L; Pickworth, Wallace B

    2015-09-01

    Verve, an oral nicotine delivery product (ONDP), was introduced by Nu Mark (Altria Client Group, Richmond VA) for smokers to use in places where smoking is prohibited. This study assessed the effect of this ONDP on plasma nicotine levels, heart rate, product satisfaction, and ability to suppress smoking urge and cigarette cravings. Thirteen daily cigarette smokers [8 men and 5 women; average age 33.4years] attended two laboratory sessions, one occurred after overnight tobacco abstinence. Plasma samples were collected before and after ONDP use and measured for nicotine. In non-abstinent smokers, mean plasma nicotine levels increased from 18.3 to 21.0ng/mL. In abstinent smokers, average nicotine levels increased from 3.1 to 4.5ng/mL. After overnight tobacco abstinence, ONDP use significantly (p<0.01) increased heart rate from 69beats per minute (bpm) to 75bpm; while urge to smoke decreased significantly (p<0.01) from a score of 8.6 to 4.9. Participants indicated moderate product satisfaction that was not changed by tobacco abstinence. Analysis of unused ONDP revealed total nicotine levels of 1.68±0.09mg/disc. Spent ONDP discs were also analyzed to determine % nicotine liberated during chewing; results were 80% in the non-abstinent and 82% in the abstinent conditions (ns). Our study results indicate that ONDP use can increase plasma nicotine levels and heart rate and reduce cigarette cravings in abstinent smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Aerobic rice mechanization: techniques for crop establishment

    Science.gov (United States)

    Khusairy, K. M.; Ayob, H.; Chan, C. S.; Fauzi, M. I. Mohamed; Mohamad Fakhrul, Z. O.; Shahril Shah, G. S. M.; Azlan, O.; Rasad, M. A.; Hashim, A. M.; Arshad, Z.; E, E. Ibrahim; Saifulizan, M. N.

    2015-12-01

    Rice being the staple food crops, hundreds of land races in it makes the diversity of rice crops. Aerobic rice production was introduced which requires much less water input to safeguard and sustain the rice production and conserve water due to decreasing water resources, climatic changes and competition from urban and industrial users. Mechanization system plays an important role for the success of aerobic rice cultivation. All farming activities for aerobic rice production are run on aerobic soil conditions. Row seeder mechanization system is developed to replace conventional seeding technique on the aerobic rice field. It is targeted for small and the large scale aerobic rice farmers. The aero - seeder machine is used for the small scale aerobic rice field, while the accord - seeder is used for the large scale aerobic rice field. The use of this mechanization machine can eliminate the tedious and inaccurate seeding operations reduce labour costs and increases work rate. The machine is easy to operate and it can increase crop establishment rate. It reduce missing hill, increasing planting and crop with high yield can be produce. This machine is designed for low costs maintenance and it is easy to dismantle and assemble during maintenance and it is safe to be used.

  19. Quinones in aerobic and anaerobic mitochondria

    NARCIS (Netherlands)

    van der Klei, S.A.

    2009-01-01

    Ubiquinone (UQ), also known as coenzyme Q, is a ubiquitous quinone and is known to have several functions. One of these functions is electron carrier in the mitochondrial electron transport chain of aerobically functioning bacteria and eukaryotes. In contrast to this aerobically functioning quinone,

  20. 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

  1. High reinforcing efficacy of nicotine in non-human primates.

    Directory of Open Access Journals (Sweden)

    Bernard Le Foll

    Full Text Available Although tobacco appears highly addictive in humans, there has been persistent controversy about the ability of its psychoactive ingredient nicotine to induce self-administration behavior in laboratory animals, bringing into question nicotine's role in reinforcing tobacco smoking. Because of ethical difficulties in inducing nicotine dependence in naïve human subjects, we explored reinforcing effects of nicotine in experimentally-naive non-human primates given access to nicotine for periods of time up to two years. Five squirrel monkeys with no experimental history were allowed to intravenously self-administer nicotine by pressing one of two levers. The number of presses on the active lever needed to obtain each injection was fixed (fixed-ratio schedule or increased progressively with successive injections during the session (progressive-ratio schedule, allowing evaluation of both reinforcing and motivational effects of nicotine under conditions of increasing response cost. Over time, a progressive shift toward high rates of responding on the active lever, but not the inactive lever, developed. The monkeys' behavior was clearly directed toward nicotine self-administration, rather than presentation of environmental stimuli associated with nicotine injection. Both schedules of reinforcement revealed a high motivation to self-administer nicotine, with monkeys continuing to press the lever when up to 600 lever-presses were needed for each injection of nicotine. Thus, nicotine, by itself, in the absence of behavioral or drug-exposure history, is a robust and highly effective reinforcer of drug-taking behavior in a non-human primate model predictive of human behavior. This supports the use of nicotinic ligands for the treatment of smokers, and this novel preclinical model offers opportunities to test future medications for the treatment of nicotine dependence.

  2. Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability

    Science.gov (United States)

    Fowler, Christie D.; Kenny, Paul J.

    2013-01-01

    Nicotine stimulates brain reward circuitries, most prominently the mesocorticolimbic dopamine system, and this action is considered critical in establishing and maintaining the tobacco smoking habit. Compounds that attenuate nicotine reward are considered promising therapeutic candidates for tobacco dependence, but many of these agents have other actions that limit their potential utility. Nicotine is also highly noxious, particularly at higher doses, and aversive reactions to nicotine after initial exposure can decrease the likelihood of developing a tobacco habit in many first time smokers. Nevertheless, relatively little is known about the mechanisms of nicotine aversion. The purpose of this review is to present recent new insights into the neurobiological mechanisms that regulate avoidance of nicotine. First, the role of the mesocorticolimbic system, so often associated with nicotine reward, in regulating nicotine aversion is highlighted. Second, genetic variation that modifies noxious responses to nicotine and thereby influences vulnerability to tobacco dependence, in particular variation in the CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptor (nAChR) subunit gene cluster, will be discussed. Third, the role of the habenular complex in nicotine aversion, primarily medial habenular projections to the interpeduncular nucleus (IPN) but also lateral habenular projections to rostromedial tegmental nucleus (RMTg) and ventral tegmental area (VTA) are reviewed. Forth, brain circuits that are enriched in nAChRs, but whose role in nicotine avoidance has not yet been assessed, will be proposed. Finally, the feasibility of developing novel therapeutic agents for tobacco dependence that act not by blocking nicotine reward but by enhancing nicotine avoidance will be considered. PMID:24055497

  3. 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

  4. Nicotine Induces Podocyte Apoptosis through Increasing Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Xiqian Lan

    Full Text Available Cigarette smoking plays an important role in the progression of chronic kidney disease (CKD. Nicotine, one of the major components of cigarette smoking, has been demonstrated to increase proliferation of renal mesangial cells. In this study, we examined the effect of nicotine on podocyte injury.To determine the expression of nicotinic acetylcholine receptors (nAChR subunits in podocytes, cDNAs and cell lysate of cultured human podocytes were used for the expression of nAChR mRNAs and proteins, respectively; and mouse renal cortical sections were subjected to immunofluorescant staining. We also studied the effect of nicotine on podocyte nephrin expression, reactive oxygen species (ROS generation (via DCFDA loading followed by fluorometric analysis, proliferation, and apoptosis (morphologic assays. We evaluated the effect of nicotine on podocyte downstream signaling including phosphorylation of ERK1/2, JNK, and p38 and established causal relationships by using respective inhibitors. We used nAChR antagonists to confirm the role of nicotine on podocyte injury.Human podocytes displayed robust mRNA and protein expression of nAChR in vitro studies. In vivo studies, mice renal cortical sections revealed co-localization of nAChRs along with synaptopodin. In vitro studies, nephrin expression in podocyte was decreased by nicotine. Nicotine stimulated podocyte ROS generation; nonetheless, antioxidants such as N-acetyl cysteine (NAC and TEMPOL (superoxide dismutase mimetic agent inhibited this effect of nicotine. Nicotine did not modulate proliferation but promoted apoptosis in podocytes. Nicotine enhanced podocyte phosphorylation of ERK1/2, JNK, and p38, and their specific inhibitors attenuated nicotine-induced apoptosis. nAChR antagonists significantly suppressed the effects of nicotine on podocyte.Nicotine induces podocyte apoptosis through ROS generation and associated downstream MAPKs signaling. The present study provides insight into molecular

  5. Effects of stage of maturity at harvest, wilting and LAB inoculant on aerobic stability of wheat silages

    DEFF Research Database (Denmark)

    Weinberg, Z.G.; Khanal, Prabhat; Chen, Y.

    2010-01-01

    The objective was to study effects of cultivar, stage of maturity at harvest, wilting, and addition of lactic acid bacterial (LAB) inoculant at ensiling, and their interactions, on the aerobic stability of wheat silages. Wheat of two cultivars, harvested at the flowering or the milk stage...... of maturity were ensiled in mini-silos, either directly after cutting (DC) or after wilting (W). After 2-7 months of storage, silages were subjected to a 7-day aerobic stability test during which changes in chemical composition, dry matter (DM) and neutral detergent fiber (aNDF) digestibility, and temperature...... to the results with cultivar, stage of maturity, wilting and inoculant as main effects, as well as their interactions. Cultivar and LAB inoculant had effects on silage composition and aerobic stability, with stage of maturity having an effect on aerobic losses, whereas wilting did not have effects on aerobic...

  6. 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...

  7. Docking to flexible nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  8. Nicotinic Acetylcholine Receptors in Sensory Cortex

    Science.gov (United States)

    Metherate, Raju

    2004-01-01

    Acetylcholine release in sensory neocortex contributes to higher-order sensory function, in part by activating nicotinic acetylcholine receptors (nAChRs). Molecular studies have revealed a bewildering array of nAChR subtypes and cellular actions; however, there is some consensus emerging about the major nAChR subtypes and their functions in…

  9. The Oncogenic Functions of Nicotinic Acetylcholine Receptors

    Directory of Open Access Journals (Sweden)

    Yue Zhao

    2016-01-01

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are ion channels that are expressed in the cell membrane of all mammalian cells, including cancer cells. Recent findings suggest that nAChRs not only mediate nicotine addiction in the brain but also contribute to the development and progression of cancers directly induced by nicotine and its derived carcinogenic nitrosamines whereas deregulation of the nAChRs is observed in many cancers, and genome-wide association studies (GWAS indicate that SNPs nAChRs associate with risks of lung cancers and nicotine addiction. Emerging evidences suggest nAChRs are posited at the central regulatory loops of numerous cell growth and prosurvival signal pathways and also mediate the synthesis and release of stimulatory and inhibitory neurotransmitters induced by their agonists. Thus nAChRs mediated cell signaling plays an important role in stimulating the growth and angiogenic and neurogenic factors and mediating oncogenic signal transduction during cancer development in a cell type specific manner. In this review, we provide an integrated view of nAChRs signaling in cancer, heightening on the oncogenic properties of nAChRs that may be targeted for cancer treatment.

  10. Antimyopathic effects of carnitine and nicotine.

    Science.gov (United States)

    Laviano, Alessandro; Meguid, Michael M; Guijarro, Ana; Muscaritoli, Maurizio; Cascino, Antonia; Preziosa, Isabella; Molfino, Alessio; Rossi Fanelli, Filippo

    2006-07-01

    The clinical course of most chronic diseases is associated with declined energy intake and nutrient-resistant progressive myopathy, characterized by accelerated proteolysis and impaired function. This anorexia/cachexia syndrome leads to deterioration of quality of life, and increased morbidity and mortality. The clinical efficacy of currently available therapeutic strategies is limited and more effective treatments are needed. Chronic systemic inflammation, triggered and sustained by cytokines, and increased oxidative stress contribute to the pathogenesis of the anorexia/cachexia syndrome. Carnitine and nicotine have recently been tested as immunomodulating and antioxidant agents. In particular, carnitine supplementation has been shown to reduce chronic inflammation and oxidative stress in hemodialysis patients and, in cancer patients, yielding to reduced fatigue and improved outcome. Nicotine is able to induce the anti-inflammatory activity of the vagus nerve. In animal models of sepsis and cancer, the nicotine-induced supplementation resulted in better protection of nutritional status and improved survival. In the continuous effort to develop more efficacious strategies against the anorexia/cachexia syndrome, carnitine and nicotine may represent a further therapeutic tool. More clinical studies are needed, however, before their use can be routinely suggested.

  11. Differences in Cold Adaptation of Bacillus subtilis under Anaerobic and Aerobic Conditions▿

    Science.gov (United States)

    Beranová, Jana; Mansilla, María C.; de Mendoza, Diego; Elhottová, Dana; Konopásek, Ivo

    2010-01-01

    Bacillus subtilis, which grows under aerobic conditions, employs fatty acid desaturase (Des) to fluidize its membrane when subjected to temperature downshift. Des requires molecular oxygen for its activity, and its expression is regulated by DesK-DesR, a two-component system. Transcription of des is induced by the temperature downshift and is decreased when membrane fluidity is restored. B. subtilis is also capable of anaerobic growth by nitrate or nitrite respiration. We studied the mechanism of cold adaptation in B. subtilis under anaerobic conditions that were predicted to inhibit Des activity. We found that in anaerobiosis, in contrast to aerobic growth, the induction of des expression after temperature downshift (from 37°C to 25°C) was not downregulated. However, the transfer from anaerobic to aerobic conditions rapidly restored the downregulation. Under both aerobic and anaerobic conditions, the induction of des expression was substantially reduced by the addition of external fluidizing oleic acid and was fully dependent on the DesK-DesR two-component regulatory system. Fatty acid analysis proved that there was no desaturation after des induction under anaerobic conditions despite the presence of high levels of the des protein product, which was shown by immunoblot analysis. The cold adaptation of B. subtilis in anaerobiosis is therefore mediated exclusively by the increased anteiso/iso ratio of branched-chain fatty acids and not by the temporarily increased level of unsaturated fatty acids that is typical under aerobic conditions. The degrees of membrane fluidization, as measured by diphenylhexatriene fluorescence anisotropy, were found to be similar under both aerobic and anaerobic conditions. PMID:20581210

  12. 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.

  13. Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization

    Science.gov (United States)

    Tapper, Andrew R.; McKinney, Sheri L.; Nashmi, Raad; Schwarz, Johannes; Deshpande, Purnima; Labarca, Cesar; Whiteaker, Paul; Marks, Michael J.; Collins, Allan C.; Lester, Henry A.

    2004-11-01

    The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with α4 nicotinic subunits containing a single point mutation, Leu9' --> Ala9' in the pore-forming M2 domain, rendering α4* receptors hypersensitive to nicotine. Selective activation of α4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of α4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization.

  14. Aerobic training in myotonia congenita

    DEFF Research Database (Denmark)

    Andersen, Grete; Løkken, Nicoline; Vissing, John

    2017-01-01

    INTRODUCTION: Exercise has not been investigated in myotonia congenita (MC). We investigated whether regular aerobic training can reduce myotonia and improve fitness. METHODS: Untrained patients with MC (age: 24-62 years; n = 6) completed 28 ± 3 sessions of 30-minute cycle ergometer training at 75......% of maximal capacity for 11 ± 1 weeks. Fitness was evaluated by maximal oxygen uptake. The level of myotonia was assessed by the Myotonia Behavior Scale, 14 step stair test, timed up and go test, and hand and eye closure-open tests. RESULTS: Training increased fitness by 9% (95% confidence interval [CI], 1......-17%; P = 0.02) and maximal workload by 10% (95% CI, 3-18%; P = 0.03). None of the myotonia tests changed in a clinically meaningful way. CONCLUSIONS: Regular endurance training improves fitness and maximal workload performance in patients with MC. The lack of creatine kinase elevations indicates...

  15. Dynamics Associated with Prolonged Ensiling and Aerobic Deterioration of Total Mixed Ration Silage Containing Whole Crop Corn

    Directory of Open Access Journals (Sweden)

    Huili Wang

    2016-01-01

    Full Text Available This study investigated the dynamics associated with prolonged ensiling and aerobic deterioration of whole crop corn (WCC silages and total mixed ration (TMR silages containing WCC (C-TMR silages to clarify the differences that account for the enhanced aerobic stability of TMR silages. Laboratory-scale barrel silos were randomly opened after 7, 14, 28, and 56 d of ensiling and were subjected to analyses of fermentation quality, microbial and temperature dynamics during aerobic exposure. WCC and C-TMR silages were both well preserved and microorganisms were inhibited with prolonged ensiling, including lactic acid bacteria. Yeast were inhibited to below the detection limit of 500 cfu/g fresh matter within 28 d of ensiling. Aerobic stability of both silages was enhanced with prolonged ensiling, whereas C-TMR silages were more aerobically stable than WCC silages for the same ensiling period. Besides the high moisture content, the weak aerobic stability of WCC silage is likely attributable to the higher lactic acid content and yeast count, which result from the high water-soluble carbohydrates content in WCC. After silo opening, yeast were the first to propagate and the increase in yeast levels is greater than that of other microorganisms in silages before deterioration. Besides, increased levels of aerobic bacteria were also detected before heating of WCC silages. The temperature dynamics also indicated that yeast are closely associated with the onset of the aerobic deterioration of C-TMR silage, whereas for WCC silages, besides yeast, aerobic bacteria also function in the aerobic deterioration. Therefore, the inclusion of WCC might contribute to the survival of yeast during ensiling but not influence the role of yeast in deterioration of C-TMR silages.

  16. 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

  17. The FAAH inhibitor URB-597 interferes with cisplatin- and nicotine-induced vomiting in the Suncus murinus (house musk shrew).

    Science.gov (United States)

    Parker, L A; Limebeer, C L; Rock, E M; Litt, D L; Kwiatkowska, M; Piomelli, D

    2009-04-20

    Considerable evidence implicates the endocannabinoid system as a neuromodulator of nausea and vomiting. The action of anandamide (AEA) can be prolonged by inhibiting its degradation, through the use of URB597 (URB), a Fatty Acid Amide Hydrolase (FAAH) enzyme inhibitor. Here we present evidence that the FAAH inhibitor, URB, interferes with cisplatin- and nicotine-induced vomiting in the Suncus murinus. In Experiment 1, shrews were injected with URB (0.9 mg/kg) or vehicle 120 min prior to the behavioral testing. They received a second injection of AEA (5 mg/kg) or vehicle 15 min prior to being injected with cisplatin (20 mg/kg) or saline and the number of vomiting episodes were counted for 60 min. In Experiment 2, shrews were injected with vehicle or URB (0.9 mg/kg) 120 min prior to receiving an injection of nicotine (5 mg/kg) or saline and the number of vomiting episodes were counted for 15 min. Experiment 3 evaluated the potential of the CB(1) antagonist, SR141716, to reverse the effect of URB on nicotine-induced vomiting. URB attenuated vomiting produced by cisplatin and nicotine and the combination of URB+AEA suppressed vomiting produced by cisplatin. The effect of URB on nicotine-induced vomiting was reversed by SR141716. These data suggest that the EC system plays a tonic role in the regulation of toxin-induced vomiting.

  18. Effects of nicotine on bone during orthodontic tooth movement in male rats. Histological and immunohistochemical study.

    Science.gov (United States)

    Bakathir, Manal A; Linjawi, Amal I; Omar, Samia S; Aboqura, Ahad B; Hassan, Ali H

    2016-10-01

    To investigate the effects of nicotine on orthodontic tooth movement and accompanying histological and immunohistochemical changes in rats. An experimental study conducted at King Abdulaziz University, Jeddah, Saudi Arabia between 2013 and 2014. Thirty-two rats randomly divided into 4 groups. Three were experimental, received daily nicotine injections: group A: 0.37 mg/kg, group B: 0.57 mg/kg, and group C: 0.93 mg/kg. The control group  (group D) received a daily injection of 0.5 mL saline. All rats were subjected to 30 g of orthodontic force on the maxillary left first molars and incisors using a nickel-titanium closed-coil spring. The distance between the 2 teeth was assessed before and after 14 days of force application. Histological, immunohistochemical, and histomorphometric assessments were performed on sections from groups C and D.  Groups C (p less than 0.001) and D (p less than 0.001) showed the significantly greatest and least amounts of tooth movement . The results were statistically dose-dependent. Unbalanced resorption-apposition bone remodeling patterns and increased osteoclast cell distribution were observed in the nicotine group with significantly smaller percentages of bone surface areas mesially and distally (p less than 0.05). Immunohistochemical stains showed low alkaline phosphatase activity and intense tartrate-resistant acid phosphatase activity in the nicotine group.  Nicotine accelerated orthodontic tooth movement with unbalanced bone resorption and apposition patterns around the moving teeth.

  19. Nesterenkonia sp. strain F, a halophilic bacterium producing acetone, butanol, and ethanol under aerobic conditions.

    Science.gov (United States)

    Amiri, Hamid; Azarbaijani, Reza; Parsa Yeganeh, Laleh; Shahzadeh Fazeli, Abolhassan; Tabatabaei, Meisam; Salekdeh, Ghasem Hosseini; Karimi, Keikhosro

    2016-01-04

    The moderately halophilic bacterium Nesterenkonia sp. strain F, which was isolated from Aran-Bidgol Lake (Iran), has the ability to produce acetone, butanol, and ethanol (ABE) as well as acetic and butyric acids under aerobic and anaerobic conditions. This result is the first report of ABE production with a wild microorganism from a family other than Clostridia and also the first halophilic species shown to produce butanol under aerobic cultivation. The cultivation of Nesterenkonia sp. strain F under anaerobic conditions with 50 g/l of glucose for 72 h resulted in the production of 105 mg/l of butanol, 122 mg/l of acetone, 0.2 g/l of acetic acid, and 2.5 g/l of butyric acid. Furthermore, the strain was cultivated on media with different glucose concentrations (20, 50, and 80 g/l) under aerobic and anaerobic conditions. Through fermentation with a 50 g/l initial glucose concentration under aerobic conditions, 66 mg/l of butanol, 125 mg/l of acetone, 291 mg/l of ethanol, 5.9 g/l of acetic acid, and 1.2 g/l of butyric acid were produced. The enzymes pertaining to the fermentation pathway in the strain were compared with the enzymes of Clostridium spp., and the metabolic pathway of fermentation used by Nesterenkonia sp. strain F was investigated.

  20. Serum nicotine level among various tobacco users: A study

    Directory of Open Access Journals (Sweden)

    Dayanandam Mala

    2016-01-01

    Full Text Available Introduction: The use of tobacco and its products has increased in the population over the past two decades, resulting in considerable systemic exposure to nicotine. Aims and Objectives: To estimate and compare the serum nicotine levels among smokers and gutkha chewers, along with the effect of nicotine replacement therapy on serum nicotine levels between them. Materials and Methods: Forty individuals were selected and divided into two groups with 20 individuals in each group. First group included individuals with a smoking habit, whereas the second group included individuals with the habit of chewing gutkha exclusively. Four blood samples were collected from all the participants in both the groups and subjected to serum nicotine estimation. Two blood samples were obtained (first sample after 30 min and the next sample after 60 min following smoking/chewing on the first day, and the other two were obtained after 24 h of tobacco abstinence (after 24 h all the participants were asked to chew nicotine chewing gums each containing 2 mg of nicotine. Statistical Analysis Used: The particulars of age, frequency of habit (smoking and chewing gutkha, and serum nicotine levels before and after replacement therapy (nicotine chewing gum were recorded and analyzed statistically by cross-tabulation for calculation of mean and frequency. Results: The serum concentration of nicotine in smokers at 30 min after smoking ranged 120-309 ng/ml and at 60 min ranged 29-77 ng/ml. In group 1, individuals′ serum nicotine concentration after replacement therapy with nicotine chewing gum ranged 29-77 ng/ml at 30 min and 1-6 ng/ml at 60 min. Serum concentration of nicotine at 30 min after chewing gutkha ranged 86-200 ng/ml and at 60 min ranged 61-102 ng/ml. The serum nicotine concentration in group 2 individuals at 30 min following chewing nicotine gum ranged 24-55 ng/ml and at 60 min ranged 0-3 ng/ml. Conclusion: Serum nicotine concentration in chewers was less at 30 min

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

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    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.

  2. 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.

  3. Nicotine activates TRPM5-dependent and independent taste pathways.

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    Oliveira-Maia, Albino J; Stapleton-Kotloski, Jennifer R; Lyall, Vijay; Phan, Tam-Hao T; Mummalaneni, Shobha; Melone, Pamela; Desimone, John A; Nicolelis, Miguel A L; Simon, Sidney A

    2009-02-03

    The orosensory responses elicited by nicotine are relevant for the development and maintenance of addiction to tobacco products. However, although nicotine is described as bitter tasting, the molecular and neural substrates encoding the taste of nicotine are unclear. Here, rats and mice were used to determine whether nicotine activates peripheral and central taste pathways via TRPM5-dependent mechanisms, which are essential for responses to other bitter tastants such as quinine, and/or via nicotinic acetylcholine receptors (nAChRs). When compared with wild-type mice, Trpm5(-/-) mice had reduced, but not abolished, chorda tympani (CT) responses to nicotine. In both genotypes, lingual application of mecamylamine, a nAChR-antagonist, inhibited CT nerve responses to nicotine and reduced behavioral responses of aversion to this stimulus. In accordance with these findings, rats were shown to discriminate between nicotine and quinine presented at intensity-paired concentrations. Moreover, rat gustatory cortex (GC) neural ensemble activity could also discriminate between these two bitter tastants. Mecamylamine reduced both behavioral and GC neural discrimination between nicotine and quinine. In summary, nicotine elicits taste responses through peripheral TRPM5-dependent pathways, common to other bitter tastants, and nAChR-dependent and TRPM5-independent pathways, thus creating a unique sensory representation that contributes to the sensory experience of tobacco products.

  4. Neuropeptide systems and new treatments for nicotine addiction.

    Science.gov (United States)

    Bruijnzeel, Adriaan W

    2017-05-01

    The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking. The reviewed studies indicate that several drugs that target neuropeptide systems diminish the rewarding effects of nicotine by preventing the activation of dopaminergic systems. Other peptide-based drugs diminish the hyperactivity of brain stress systems and diminish withdrawal-associated symptom severity. Blockade of hypocretin-1 and nociceptin receptors and stimulation of galanin and neurotensin receptors diminishes the rewarding effects of nicotine. Both corticotropin-releasing factor type 1 and kappa-opioid receptor antagonists diminish dysphoria and anxiety-like behavior associated with nicotine withdrawal and inhibit stress-induced reinstatement of nicotine seeking. Furthermore, blockade of vasopressin 1b receptors diminishes dysphoria during nicotine withdrawal, and melanocortin 4 receptor blockade prevents stress-induced reinstatement of nicotine seeking. The role of neuropeptide systems in nicotine-primed and cue-induced reinstatement is largely unexplored, but there is evidence for a role of hypocretin-1 receptors in cue-induced reinstatement of nicotine seeking. Drugs that target neuropeptide systems might decrease the euphoric effects of smoking and improve relapse rates by diminishing withdrawal symptoms and improving stress resilience.

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

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    Stošić Dušan K.

    2007-01-01

    Full Text Available The plant alkaloid, nicotine, is a strongly toxic heterocyclic compound: the lethal dose for an adult human being (40-60 mg is importantly lower in comparison with the other known poisons such as arsenic or strychni­ne. Cigarettes represent "the most toxic and addictive form of nicotine". Besides the negative effects of nicotine on public health produced by self-administration, recently another potentially very dangerous effect has been recognized: because of its miscibility with water, nicotine can be found in industrial wastewaters, and consequently, in groundwater. Therefore, the problem of nicotine removal from aqueous solutions has became an interesting topic. In this work, the removal of nicotine has been probed by adsorption on solid materials. Adsorption of nicotine on different zeolites (clinoptilolite, ZSM-5 and β zeolite and on activated carbon was investigated from aqueous solutions, at 298 K. The obtained results are presented as adsorption isotherms: the amount of adsorbed nicotine as a function of equilibrium concentration. These data were obtained from the residual amount of nicotine in the aqueous phase, by the use of UV spectroscopy. The highest amounts of adsorbed nicotine was found for activated carbon and p zeolite (~ mmol·g-1. The attempt to modify the adsorption properties of ZSM-5 zeolite has been also done: ZSM-5 was modified by ion-exchange with VIII group metal (Cu2+ and Fe3+. In addition, the adsorption of nicotine on ZSM-5 zeolite with different Si/Al ratios has been done. It has been noticed that ion-exchange did not improve the adsorption possibilities, while the adsorption was importantly lower in the case of higher silicon content in ZMS-5 structure. 13C NMR spectra were collected for suspensions formed of solid adsorbent and aqueous solution of nicotine; in this way, the part of nicotine molecule which is most probably connected with the adsorbent was recognized.

  6. 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.

  7. Characterization of the Dominant Aerobic Microorganism in Cattle Feedlot Waste

    Science.gov (United States)

    Hrubant, G. R.

    1973-01-01

    The dominant aerobic microorganism in cattle feedlot waste (FLW) is a corynebacterium. It is ubiquitous to FLW except on sites where antibiotics are a constant part of the animals' diet. The organism requires DL-aspartic acid as its nitrogen source for growth, and individual strains also require or are stimulated by L-tyrosine; acetate serves as the carbon source. Amylolytic activity is weak; protease, lipase, and cellulase activities are nil. Despite the abundance of the organism, it probably does not decompose the waste appreciably. Images PMID:4127426

  8. Aerobic biotransformation of polyfluoroalkyl phosphate esters (PAPs) in soil

    International Nuclear Information System (INIS)

    Liu, Chen; Liu, Jinxia

    2016-01-01

    Microbial transformation of polyfluoroalkyl phosphate esters (PAPs) into perfluorocarboxylic acids (PFCAs) has recently been confirmed to occur in activated sludge and soil. However, there lacks quantitative information about the half-lives of the PAPs and their significance as the precursors to PFCAs. In the present study, the biotransformation of 6:2 and 8:2 diPAP in aerobic soil was investigated in semi-dynamics reactors using improved sample preparation methods. To develop an efficient extraction method for PAPs, six different extraction solvents were compared, and the phenomenon of solvent-enhanced hydrolysis was investigated. It was found that adding acetic acid could enhance the recoveries of the diPAPs and inhibit undesirable hydrolysis during solvent extraction of soil. However 6:2 and 8:2 monoPAPs, which are the first breakdown products from diPAPs, were found to be unstable in the six solvents tested and quickly hydrolyzed to form fluorotelomer alcohols. Therefore reliable measurement of the monoPAPs from a live soil was not achievable. The apparent DT 50 values of 6:2 diPAP and 8:2 diPAP biotransformation were estimated to be 12 and > 1000 days, respectively, using a double first-order in parallel model. At the end of incubation of day 112, the major degradation products of 6:2 diPAP were 5:3 fluorotelomer carboxylic acid (5:3 acid, 9.3% by mole), perfluoropentanoic acid (PFPeA, 6.4%) and perfluorohexanoic acid (PFHxA, 6.0%). The primary product of 8:2 diPAP was perfluorooctanoic acid (PFOA, 2.1%). The approximately linear relationship between the half-lives of eleven polyfluoroalkyl and perfluoroalkyl substances (PFASs, including 6:2 and 8:2 diPAPs) that biotransform in aerobic soils and their molecular weights suggested that the molecular weight is a good indicator of the general stability of low-molecular-weight PFAS-based compounds in aerobic soils. - Highlights: • Biotransformation of 6:2 and 8:2 diPAPs in an aerobic soil was investigated.

  9. Low aerobic fitness in Brazilian adolescents

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    Diego Augusto Santos Silva

    2015-04-01

    Full Text Available INTRODUCTION: aerobic fitness is considered one of the most important components of health-related physical fitness, with low levels related to increased risk of premature death from all causes, especially cardiovascular diseases. OBJECTIVE: to identify the characteristics of adolescents at higher risk of low levels of aerobic fitness. METHODS: the study included 696 adolescents 15-17 years of age enrolled in public high schools of Florianópolis, southern Brazil. This cross-sectional epidemiological study was conducted in Florianópolis, Santa Catarina, Brazil. Aerobic fitness was measured using the modified Canadian Aerobic Fitness Test mCAFT. Sociodemographic gender, age, school grade, paternal and maternal schooling, socioeconomic status, and anthropometric variables body weight, height, triceps and subscapular skinfold thickness, sexual maturation, physical activity, sedentary behavior, and eating habits were collected. RESULTS: it was found that 31.5% of adolescents had low aerobic fitness levels, being higher in boys 49.2% compared to girls 20.6%. Moreover, girls with sedentary behavior, overweight and high body fat percentage were the groups most likely to have inadequate aerobic fitness. In males, the groups most likely to have inadequate aerobic fitness were those whose parents studied more than eight years, those with low levels of physical activity, and those with inadequate nutrition and excessive body fat. CONCLUSION: low aerobic fitness levels were present in one third of adolescents and was more prevalent in boys. Lifestyle changes, including replacement of sedentary behaviors by physical and sport activities , may assist in improving the aerobic fitness of Brazilian adolescents.

  10. Nicotine yield from machine-smoked cigarettes and nicotine intakes in smokers: evidence from a representative population survey.

    Science.gov (United States)

    Jarvis, M J; Boreham, R; Primatesta, P; Feyerabend, C; Bryant, A

    2001-01-17

    The relevance of nicotine yields from machine-smoked cigarettes for quantifying smokers' nicotine intakes and exposure to cigarette toxins has been called into question. However, most studies of the relationship between nicotine yield and nicotine intake have been on relatively small and unrepresentative samples and have included few smokers of "ultra-low" brands (i.e., those yielding around 1 mg of tar and 0.1 mg of nicotine). We examined the relationship between salivary cotinine (a major metabolite of nicotine) concentrations and nicotine yields of machine-smoked cigarettes in a nationally representative sample of 2031 adult smokers of manufactured cigarettes surveyed in the 1998 Health Survey for England. We used standard linear regression techniques to examine associations and two-sided tests of statistical significance. Cotinine concentrations varied widely between smokers at any level of nominal brand nicotine yield. On average, cotinine levels were slightly lower in smokers of lower nicotine-yielding brands, but these smokers differed in terms of sex, socioeconomic profile, and cigarette consumption. After we controlled for potential confounders, nicotine yield from the brand smoked accounted for only 0.79% of the variation in saliva cotinine concentrations. Nicotine intake per cigarette smoked, as estimated from salivary cotinine level, did not correspond with machine-smoked yields at any level of nicotine yield. Nicotine intake per cigarette was about eight times greater than machine-smoked yields at the lowest deliveries (1.17 mg estimated nicotine intake per cigarette from brands averaging 0.14-mg delivery from machine smoking) and 1.4 times greater for the highest yield cigarettes (1.31-mg estimated nicotine intake per cigarette from brands averaging 0.91 mg from machine smoking). Smokers' tendency to regulate nicotine intake vitiates potential health gains from lower tar and nicotine cigarettes. Current approaches to characterizing tar and nicotine

  11. Aerobic biotransformation of polyfluoroalkyl phosphate esters (PAPs) in soil.

    Science.gov (United States)

    Liu, Chen; Liu, Jinxia

    2016-05-01

    Microbial transformation of polyfluoroalkyl phosphate esters (PAPs) into perfluorocarboxylic acids (PFCAs) has recently been confirmed to occur in activated sludge and soil. However, there lacks quantitative information about the half-lives of the PAPs and their significance as the precursors to PFCAs. In the present study, the biotransformation of 6:2 and 8:2 diPAP in aerobic soil was investigated in semi-dynamics reactors using improved sample preparation methods. To develop an efficient extraction method for PAPs, six different extraction solvents were compared, and the phenomenon of solvent-enhanced hydrolysis was investigated. It was found that adding acetic acid could enhance the recoveries of the diPAPs and inhibit undesirable hydrolysis during solvent extraction of soil. However 6:2 and 8:2 monoPAPs, which are the first breakdown products from diPAPs, were found to be unstable in the six solvents tested and quickly hydrolyzed to form fluorotelomer alcohols. Therefore reliable measurement of the monoPAPs from a live soil was not achievable. The apparent DT50 values of 6:2 diPAP and 8:2 diPAP biotransformation were estimated to be 12 and > 1000 days, respectively, using a double first-order in parallel model. At the end of incubation of day 112, the major degradation products of 6:2 diPAP were 5:3 fluorotelomer carboxylic acid (5:3 acid, 9.3% by mole), perfluoropentanoic acid (PFPeA, 6.4%) and perfluorohexanoic acid (PFHxA, 6.0%). The primary product of 8:2 diPAP was perfluorooctanoic acid (PFOA, 2.1%). The approximately linear relationship between the half-lives of eleven polyfluoroalkyl and perfluoroalkyl substances (PFASs, including 6:2 and 8:2 diPAPs) that biotransform in aerobic soils and their molecular weights suggested that the molecular weight is a good indicator of the general stability of low-molecular-weight PFAS-based compounds in aerobic soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. 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.

  13. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine.

    Science.gov (United States)

    Perez, Erika; Quijano-Cardé, Natalia; De Biasi, Mariella

    2015-09-01

    Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol.

  14. 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.

  15. 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

  16. Galantamine, an Acetylcholinesterase Inhibitor and Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors, Attenuates Nicotine Taking and Seeking in Rats

    Science.gov (United States)

    Hopkins, Thomas J; Rupprecht, Laura E; Hayes, Matthew R; Blendy, Julie A; Schmidt, Heath D

    2012-01-01

    Current smoking cessation pharmacotherapies have limited efficacy in preventing relapse and maintaining abstinence during withdrawal. Galantamine is an acetylcholinesterase inhibitor that also acts as a positive allosteric modulator of nicotinic acetylcholine receptors. Galantamine has recently been shown to reverse nicotine withdrawal-induced cognitive impairments in mice, which suggests that galantamine may function to prevent relapse in human smokers. However, there are no studies examining whether galantamine administration modulates nicotine self-administration and/or reinstatement of nicotine seeking in rodents. The present experiments were designed to determine the effects of galantamine administration on nicotine taking and reinstatement of nicotine-seeking behavior, an animal model of relapse. Moreover, the effects of galantamine on sucrose-maintained responding and sucrose seeking were also examined to determine whether galantamine's effects generalized to other reinforced behaviors. An inverted U-shaped dose-response curve was obtained when animals self-administered different unit doses of nicotine with the highest responding for 0.03 mg/kg per infusion of nicotine. Acute galantamine administration (5.0 mg/kg, i.p.) attenuated nicotine self-administration when animals were maintained on either a fixed-ratio 5 (FR5) or progressive ratio (PR) schedule of reinforcement. Galantamine administration also attenuated the reinstatement of nicotine-seeking behavior. No significant effects of galantamine on sucrose self-administration or sucrose reinstatement were noted. Acetylcholinesterase inhibitors have also been shown to produce nausea and vomiting in humans. However, at doses required to attenuate nicotine self-administration, no effects of galantamine on nausea/malaise as measured by pica were noted. These results indicate that increased extracellular acetylcholine levels and/or nicotinic acetylcholine receptor stimulation is sufficient to attenuate

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

    Science.gov (United States)

    Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

    2014-01-01

    Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1–7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking. PMID:24950455

  18. 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.

  19. Nicotine acts on growth plate chondrocytes to delay skeletal growth through the alpha7 neuronal nicotinic acetylcholine receptor.

    Directory of Open Access Journals (Sweden)

    Atsuo Kawakita

    Full Text Available BACKGROUND: Cigarette smoking adversely affects endochondral ossification during the course of skeletal growth. Among a plethora of cigarette chemicals, nicotine is one of the primary candidate compounds responsible for the cause of smoking-induced delayed skeletal growth. However, the possible mechanism of delayed skeletal growth caused by nicotine remains unclarified. In the last decade, localization of neuronal nicotinic acetylcholine receptor (nAChR, a specific receptor of nicotine, has been widely detected in non-excitable cells. Therefore, we hypothesized that nicotine affect growth plate chondrocytes directly and specifically through nAChR to delay skeletal growth. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of nicotine on human growth plate chondrocytes, a major component of endochondral ossification. The chondrocytes were derived from extra human fingers. Nicotine inhibited matrix synthesis and hypertrophic differentiation in human growth plate chondrocytes in suspension culture in a concentration-dependent manner. Both human and murine growth plate chondrocytes expressed alpha7 nAChR, which constitutes functional homopentameric receptors. Methyllycaconitine (MLA, a specific antagonist of alpha7 nAChR, reversed the inhibition of matrix synthesis and functional calcium signal by nicotine in human growth plate chondrocytes in vitro. To study the effect of nicotine on growth plate in vivo, ovulation-controlled pregnant alpha7 nAChR +/- mice were given drinking water with or without nicotine during pregnancy, and skeletal growth of their fetuses was observed. Maternal nicotine exposure resulted in delayed skeletal growth of alpha7 nAChR +/+ fetuses but not in alpha7 nAChR -/- fetuses, implying that skeletal growth retardation by nicotine is specifically mediated via fetal alpha7 nAChR. CONCLUSIONS/SIGNIFICANCE: These results suggest that nicotine, from cigarette smoking, acts directly on growth plate chondrocytes to decrease

  20. 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.

  1. Cholinergic modulation of dopaminergic reward areas: upstream and downstream targets of nicotine addiction

    NARCIS (Netherlands)

    Mansvelder, H.D.; de Rover, M.; McGehee, D.S.; Brussaard, A.B.

    2003-01-01

    Nicotine reinforces smoking behaviour by activating nicotinic acetylcholine receptors in the midbrain dopaminergic reward centres. Upstream of the dopaminergic neurons nicotine induces long-term potentiation of the excitatory input to dopamine cells in the ventral tegmental area, and depresses

  2. Settling properties of aerobic granular sludge (AGS) and aerobic granular sludge molasses (AGSM)

    Science.gov (United States)

    Mat Saad, Azlina; Aini Dahalan, Farrah; Ibrahim, Naimah; Yasina Yusuf, Sara; Aqlima Ahmad, Siti; Khalil, Khalilah Abdul

    2018-03-01

    Aerobic granulation technology is applied to treat domestic and industrial wastewater. The Aerobic granular sludge (AGS) cultivated has strong properties that appears to be denser and compact in physiological structure compared to the conventional activated sludge. It offers rapid settling for solid:liquid separation in wastewater treatment. Aerobic granules were developed using sequencing batch reactor (SBR) with intermittent aerobic - anaerobic mode with 8 cycles in 24 hr. This study examined the settling velocity performance of cultivated aerobic granular sludge (AGS) and aerobic granular sludge molasses (AGSM). The elemental composition in both AGS and AGSM were determined using X-ray fluorescence (XRF). The results showed that AGSM has higher settling velocity 30.5 m/h compared to AGS.

  3. 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

  4. 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.

  5. Improved treatment of nicotine addiction and emerging pulmonary drug delivery.

    Science.gov (United States)

    Islam, Nazrul; Rahman, Shafiqur

    2012-06-01

    Nicotine addiction remains the leading cause of death and disease in developed and developing nations and a major cause of mortality around the world. Currently, nicotine replacement therapies (NRTs), bupropion, and varenicline are approved by the regulatory agencies as first-line treatments for nicotine addiction. Emerging evidence indicates that varenicline and bupropion have some therapeutic limitations for treating nicotine addiction with oral route of administration. Thus, continued investigation of innovative drug delivery for nicotine addiction remains a critical priority. This review will discuss some novel strategies and future directions for pulmonary drug delivery, an emerging route of administration for smoking cessation. It is anticipated that the advancement of knowledge on pulmonary drug delivery will provide better management for nicotine addiction and other addictive disorders.

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

    DEFF Research Database (Denmark)

    Bekö, Gabriel; Morrison, G.; Weschler, Charles J.

    2017-01-01

    This study aims to elucidate in greater detail the dermal uptake of nicotine from air or from nicotine-exposed clothes, which was demonstrated recently in a preliminary study. Six non-smoking participants were exposed to gaseous nicotine (between 236 and 304 μg/m3 ) over 5 hours while breathing...... clothes on week 1 were now exposed wearing a set of clothes that had been exposed to nicotine. All urine was collected for 84 hours after exposure and analyzed for nicotine and its metabolites, cotinine and 3OH-cotinine. All participants except those wearing fresh clothes excreted substantial amounts...... of biomarkers, comparable to levels expected from inhalation intake. Uptake for 1 participant wearing exposed clothes exceeded estimated intake via inhalation by >50%. Biomarker excretion continued during the entire urine collection period, indicating that nicotine accumulates in the skin and is released over...

  7. 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)

  8. Aerobic Biodegradation Kinetics And Mineralization Of Six Petrodiesel/Soybean-Biodiesel Blends

    Science.gov (United States)

    The aerobic biodegradation kinetics and mineralization of six petrodiesel/soybean-biodiesel blends (B0, B20, B40, B60, B80, and B100), where B100 is 100% biodiesel, were investigated by acclimated cultures. The fatty acid methyl esters (FAMEs) of biodiesel were found to undergo ...

  9. Fate of herbicides in a shallow aerobic aquifer: A continuous field injection experiment (Vejen,Denmark)

    DEFF Research Database (Denmark)

    Broholm, Mette; Rügge, K.; Tuxen, Nina

    2001-01-01

    A continuous, natural gradient, field injection experiment, involving six herbicides and a tracer, was performed in a shallow aerobic aquifer near Vejen, Denmark. Bentazone, ()-2-(4-chloro-2-methylphenoxy) propanoic acid (MCPP), dichlorprop, isoproturon, and the dichlobenil metabolite 2,6-dichlor...

  10. Development of nanoparticle based nicotine vaccines for smoking cessation

    OpenAIRE

    Hu, Yun

    2015-01-01

    Cigarette smoking is prevalent worldwide and has consistently been the top preventable cause of many serious diseases., which result in huge mortality, morbidity, and economic loss, in recent decades. In recent years, nicotine vaccines that can induce production of nicotine specific antibodies in human have emerged as a promising medicine to treat tobacco addiction. In the past decade, there have been numerous nicotine vaccine candidates evaluated in human clinical trials, including NicVaxNi...

  11. Combination Treatment for Nicotine Dependence: State of the Science

    OpenAIRE

    INGERSOLL, KAREN S.; COHEN, JESSYE

    2005-01-01

    Both nicotine replacement and sustained-release buproprion double the odds of achieving short- and moderate-term abstinence from nicotine. However, questions remain about the efficacy of combining pharmacotherapies. Our purposes were to review the evidence for (1) combined pharmacotherapy and (2) multimodal treatment combining pharmacotherapy and behavioral treatment and to recommend combinations of treatments to reduce nicotine dependence. Combining first-line pharmacotherapies with each oth...

  12. The α7 nicotinic acetylcholine receptor complex

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Mikkelsen, Jens D

    2012-01-01

    The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds and prote...... as an increasing pipeline of specific drug candidates, enabling a more subtle manipulation of α7 nAChR function, may facilitate α7 nAChR drug development efforts....

  13. 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

  14. Nicotine vaccines for smoking cessation-present and future

    Directory of Open Access Journals (Sweden)

    Richa

    2013-01-01

    Full Text Available Background: Worldwide tobacco is the leading cause of preventable death. Anew treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This article aimed to review the mechanism of action, current status of research and future aspects for the development of vaccines against nicotine. Materials & Method: The literature search of publications indexed was carried out in PubMed, Medline, Google scholar databases. Total 25 animal trials, human trials under various phases of clinical trials, unpublished document and cross-sectional survey were reviewed. Results: This immunization will act on immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. Nicotine vaccines are irreversible, provide protection over years and need booster injections. Efficiency of the vaccines is directly related to the antibody levels which help to optimize the vaccine effect. Nicotine vaccines are today in an advanced stage of clinical evaluation trials. Conclusions: Though, nicotine vaccine has considerable therapeutic potential, they do not target the non pharmacological factors that maintain tobacco dependence. So combination of nicotine vaccine with behavioral interventions would be effective mode to motivate abstinence from tobacco use.

  15. Advances in nicotine research in Addiction Biology.

    Science.gov (United States)

    Bernardi, Rick E

    2015-09-01

    The aim of Addiction Biology is to advance our understanding of the action of drugs of abuse and addictive processes via the publication of high-impact clinical and pre-clinical findings resulting from behavioral, molecular, genetic, biochemical, neurobiological and pharmacological research. As of 2013, Addiction Biology is ranked number 1 in the category of Substance Abuse journals (SCI). Occasionally, Addiction Biology likes to highlight via review important findings focused on a particular topic and recently published in the journal. The current review summarizes a number of key publications from Addiction Biology that have contributed to the current knowledge of nicotine research, comprising a wide spectrum of approaches, both clinical and pre-clinical, at the cellular, molecular, systems and behavioral levels. A number of findings from human studies have identified, using imaging techniques, alterations in common brain circuits, as well as morphological and network activity changes, associated with tobacco use. Furthermore, both clinical and pre-clinical studies have characterized a number of mechanistic targets critical to understanding the effects of nicotine and tobacco addiction. Together, these findings will undoubtedly drive future studies examining the dramatic impact of tobacco use and the development of treatments to counter nicotine dependence. © 2015 Society for the Study of Addiction.

  16. 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.

  17. 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

  18. Prenatal to early postnatal nicotine exposure impairs central chemoreception and modifies breathing pattern in mouse neonates: a probable link to sudden infant death syndrome.

    Science.gov (United States)

    Eugenín, Jaime; Otárola, Marcelo; Bravo, Eduardo; Coddou, Claudio; Cerpa, Verónica; Reyes-Parada, Miguel; Llona, Isabel; von Bernhardi, Rommy

    2008-12-17

    Nicotine is a neuroteratogen and is the likely link between maternal cigarette smoking during pregnancy and sudden infant death syndrome (SIDS). Osmotic minipumps were implanted in 5-7 d CF1 pregnant mice to deliver nicotine bitartrate (60 mg Kg(-1) day(-1)) or saline (control) solutions for up to 28 d. Prenatal to early postnatal nicotine exposure did not modify the number of newborns per litter or their postnatal growth; however, nicotine-exposed neonates hypoventilated and had reduced responses to hypercarbia (inhalation of air enriched with 10% CO(2) for 20 min) and hypoxia (inhalation of 100% N(2) for 20 s) at postnatal days 0-3 (P0-P3). In contrast, at postnatal day 8, nicotine-exposed neonates were indistinguishable from controls. Isolated brainstem-spinal cord preparations obtained from P0 to P3 nicotine-exposed neonates showed fictive respiration with respiratory cycles longer and more irregular than those of controls, as indicated by high short- and long-term variability in Poincaré plots. In addition, their responses to acidification were reduced, indicating compromise of central chemoreception. Furthermore, the cholinergic contribution to central chemosensory responses switched from muscarinic receptor to nicotinic receptor-based mechanisms. No significant astrogliosis was detectable in the ventral respiratory group of neurons with glial fibrillary acidic protein immunohistochemistry. These results indicate that nicotine exposure affects the respiratory rhythm pattern generator and causes a decline in central chemoreception during early postnatal life. Consequently, breathing would become highly vulnerable, failing to respond to chemosensory demands. Such impairment could be related to the ventilatory abnormalities observed in SIDS.

  19. Measure nicotine dependence by the fagerström test for nicotine dependence

    OpenAIRE

    WEBER, Caroline Francieli; HATSCHBACH, Patrícia; PITHAN, Sílvia Ataide; DULLIUS, Angela Isabel dos Santos

    2017-01-01

    ABSTRACT Objective To assess the level of nicotine dependence of smokers in a university dental clinic in southern Brazil using the Fagerström Test for Nicotine Dependence and identify those who would like to quit smoking. Methods A cross-sectional study was carried out with 93 Dental School patients, who underwent a face-to-face interview with four researchers. Data was analysed using descriptive statistics and the Chi-Square test with a significance level of 5%. Results The mean age of t...

  20. Orthodontic forces add to nicotine-induced loss of periodontal bone : An in vivo and in vitro study.

    Science.gov (United States)

    Kirschneck, Christian; Proff, Peter; Maurer, Michael; Reicheneder, Claudia; Römer, Piero

    2015-05-01

    Nicotine is considered an etiologic factor for chronic inflammatory phenomena within the periodontal ligament that may result in loss of periodontal attachment. Considering that smokers account for 26% of adult and 12% of adolescent patients in orthodontic practice, we performed in vivo and in vitro studies as to whether orthodontic forces may add to the nicotine-induced loss of periodontal bone. Fourteen male rats (Fischer 344 inbred) were used. Seven of these served as controls, while the other seven received daily subcutaneous injections of 1.89 mg L-nicotine per kg body weight. Both groups were exposed to orthodontic mesialization of the first two upper left molars using a NiTi closed-coil spring, the contralateral side serving as control. Periodontal bone loss was assessed by cone-beam computed tomography (CBCT). Human periodontal fibroblasts were stressed by compression (2 g/cm(2)) and/or nicotine (3/5/7.5 µmol), and the expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-6 (IL-6), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL) was determined at the transcriptional level by quantitative real-time polymerase chain reaction (qRT-PCR) and at the translational level by enzyme-linked immunosorbent assay (ELISA). In addition, differentiation of co-cultured murine RAW264.7 cells to osteoclast-like cells was quantified by tartrate-resistant acid phosphatase (TRAP) staining. Orthodontic force application in vivo led to a significant increase in nicotine-induced periodontal bone loss, and cell compression in vitro to increased COX-2, PGE2, IL-6, and RANKL expression, reduced OPG expression, and enhanced differentiation of RAW264.7 cells to osteoclast-like cells compared to nicotine alone. Additional loss of periodontal bone must be expected during orthodontic treatment of smokers. Clinicians should inform their patients of this increased risk and refrain from performing tooth movements before cessation of

  1. Research on the corrosion inhibitors of zinc in hydrochloric acid

    Science.gov (United States)

    Sun, C. X.; Chen, Y. M.; Xu, H. W.; Huang, C. S.; Zhang, M.; Wu, J. Y.; Chen, M.; Xue, M.

    2017-06-01

    Three organic compounds were tested as zinc corrosion inhibitors in hydrochloric acid: cetyltrimethyl ammonium bromide (CTAB), nicotini acid, bromohexadecyl pyridine. The static coupon test results indicate that CTAB and bromohexadecyl pyridine offer the best zinc corrosion protection, while nicotinic acid accelerates zinc corrosion. The polarization results indicate that CTAB, nicotinic acid and bromohexadecyl pyridine induce a positive shift in the E0 of zinc in hydrochloric acid. A complex of CTAB and bromohexadecyl pyridine inhibits the corrosion of zinc in hydrochloric acid. SEM results indicate that the CTAB and bromohexadecyl pyridine formed a uniform and compact membrane on the surface of zinc that subsequently protects the zinc from effective corrosion.

  2. Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia, and airway mucus formation in vitro and in vivo.

    Science.gov (United States)

    Gundavarapu, Sravanthi; Wilder, Julie A; Mishra, Neerad C; Rir-Sima-Ah, Jules; Langley, Raymond J; Singh, Shashi P; Saeed, Ali Imran; Jaramillo, Richard J; Gott, Katherine M; Peña-Philippides, Juan Carlos; Harrod, Kevin S; McIntosh, J Michael; Buch, Shilpa; Sopori, Mohan L

    2012-09-01

    Airway mucus hypersecretion is a key pathophysiologic feature in a number of lung diseases. Cigarette smoke/nicotine and allergens are strong stimulators of airway mucus; however, the mechanism of mucus modulation is unclear. We sought to characterize the pathway by which cigarette smoke/nicotine regulates airway mucus and identify agents that decrease airway mucus. IL-13 and γ-aminobutyric acid type A receptors (GABA(A)Rs) are implicated in airway mucus. We examined the role of IL-13 and GABA(A)Rs in nicotine-induced mucus formation in normal human bronchial epithelial (NHBE) and A549 cells and secondhand cigarette smoke-induced, ovalbumin-induced, or both mucus formation in vivo. Nicotine promotes mucus formation in NHBE cells; however, the nicotine-induced mucus formation is independent of IL-13 but sensitive to the GABA(A)R antagonist picrotoxin. Airway epithelial cells express α7-, α9-, and α10-nicotinic acetylcholine receptors (nAChRs), and specific inhibition or knockdown of α7- but not α9/α10-nAChRs abrogates mucus formation in response to nicotine and IL-13. Moreover, addition of acetylcholine or inhibition of its degradation increases mucus in NHBE cells. Nicotinic but not muscarinic receptor antagonists block allergen- or nicotine/cigarette smoke-induced airway mucus formation in NHBE cells, murine airways, or both. Nicotine-induced airway mucus formation is independent of IL-13, and α7-nAChRs are critical in airway mucous cell metaplasia/hyperplasia and mucus production in response to various promucoid agents, including IL-13. In the absence of nicotine, acetylcholine might be the biological ligand for α7-nAChRs to trigger airway mucus formation. α7-nAChRs are downstream of IL-13 but upstream of GABA(A)Rα2 in the MUC5AC pathway. Acetylcholine and α7-nAChRs might serve as therapeutic targets to control airway mucus. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  3. 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.

  4. 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

  5. Nicotine increases sucrose self-administration and seeking in rats.

    Science.gov (United States)

    Grimm, Jeffrey W; Ratliff, Christine; North, Kindsey; Barnes, Jesse; Collins, Stefan

    2012-05-01

    Associations between nicotine in cigarettes and food consumption may alter the incentive value of food such that food cue-reactivity is exaggerated during abstinence from smoking. This effect may contribute to the weight gain associated with cessation of smoking. We examined the effects of nicotine (0.4 mg/kg base subcutaneous) paired (NPD) or unpaired (NUP) with 10% sucrose self-administration (SA; 0.2 ml/delivery, 1 h/day for 10 days) on SA response rate and intake as well as sucrose cue-reactivity following either 1 or 30 days of forced abstinence. Rats were administered the training dose of nicotine prior to a second, consecutive cue-reactivity session. NPD rats responded at over three times the rate for sucrose and earned nearly twice the number of sucrose deliveries as NUP rats or saline controls. Sucrose cue-reactivity was greater after 30 days versus 1 day of forced abstinence for all groups. History of nicotine exposure had no effect on sucrose cue-reactivity. However, the subsequent injection of nicotine increased sucrose cue-reactivity only in the NPD groups. There were no abstinent-dependent effects of nicotine challenge on sucrose cue-reactivity. A study conducted in parallel with water as the reinforcer revealed a less dramatic effect of nicotine on intake. There was no history or abstinence-dependent effects of nicotine on water cue-reactivity. Nicotine increases the reinforcing effects of sucrose and sucrose-paired cues when nicotine is present. An implication of these findings is that relapse to nicotine (cigarettes) could substantially elevate food cue-reactivity. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    subjective craving and neural activities in nicotine-addicted individuals using model-based functional magnetic resonance imaging (fMRI) and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced placebo design, which crossed beliefs about nicotine (told "nicotine" vs. told "no...... nicotine") with the nicotine content in a cigarette (nicotine vs. placebo) which participants smoked immediately before performing a fMRI task involving reward learning. Subjects' reported craving was measured both before smoking and after the fMRI session. We found that first, in the presence of nicotine......, smokers demonstrated significantly reduced craving after smoking when told "nicotine in cigarette" but showed no change in craving when told "no nicotine." Second, neural activity in the insular cortex related to craving was only significant when smokers were told "nicotine" but not when told "no nicotine...

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

    Science.gov (United States)

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

    2009-01-01

    The effects of acute nicotine administration (0.09 mg/kg nicotine), chronic nicotine administration (6.3 mg/kg/d nicotine for 14 d), and withdrawal from chronic nicotine administration on fear conditioning in C57BL/6 mice were examined. Mice were trained using two coterminating conditioned stimulus (30 s; 85 dB white noise)– unconditioned stimulus (2 s; 0.57 mA foot shock) pairings and tested 24 h later for contextual and cued fear conditioning. Acute nicotine administration enhanced contextual fear conditioning, chronic nicotine administration had no effect on contextual fear conditioning, and withdrawal from chronic nicotine administration impaired contextual fear conditioning. Plasma nicotine concentrations were similar after acute and chronic treatment and were within the range reported for smokers. During withdrawal, concentrations of nicotine were undetectable. An acute dose of nicotine (0.09 mg/kg) during withdrawal from chronic nicotine treatment reversed withdrawal-associated deficits in contextual fear conditioning. The results suggest that tolerance to the effects of nicotine on contextual fear conditioning develops with chronic nicotine treatment at a physiologically relevant dose, and withdrawal from this chronic nicotine treatment is associated with impairments in contextual fear conditioning. These findings provide a model of how the effects of nicotine on learning may contribute to the development and maintenance of nicotine addiction. PMID:16177040

  8. Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: effects of route and ethanol coadministration

    Science.gov (United States)

    Katner, Simon N.; Toalston, Jamie E.; Smoker, Michael P.; Rodd, Zachary A.; McBride, William J.

    2015-01-01

    Rationale Nicotine and ethanol are commonly coabused drugs, and nicotine-laced ethanol products are growing in popularity. However, little is known about time-course changes in extracellular nicotine and cotinine levels in rat models of ethanol and nicotine coabuse. Objectives The objective of the present study was to determine the time-course changes in brain levels of nicotine and cotinine following subcutaneous (SC) and intragastric (IG) nicotine administration in alcohol-preferring (P) and Wistar rats. Methods In vivo microdialysis was used to collect dialysate samples from the nucleus accumbens shell (NACsh) for nicotine and cotinine determinations, following SC administration of (−)-nicotine (0.18, 0.35, and 0.70 mg/kg) in female P and Wistar rats or IG administration of (−)-nicotine (0.35 and 0.70 mg/kg) in 15 % (v/v) ethanol or water in female P rats. Results SC nicotine produced nicotine and cotinine dialysate levels as high as 51 and 14 ng/ml, respectively. IG administration of 15 % EtOH + 0.70 mg/kg nicotine in P rats resulted in maximal nicotine and cotinine dialysate levels of 19 and 14 ng/ml, respectively, whereas administration of 0.70 mg/kg nicotine in water resulted in maximal nicotine and cotinine levels of 21 and 25 ng/ml, respectively. Nicotine and cotinine levels were detectable within the first 15 and 45 min, respectively, after IG administration. Conclusions Overall, the results of this study suggest that nicotine is rapidly adsorbed and produces relevant extracellular brain concentrations of nicotine and its pharmacologically active metabolite, cotinine. The persisting high brain concentrations of cotinine may contribute to nicotine addiction. PMID:25038869

  9. Impact of nicotine metabolism on nicotine's pharmacological effects and behavioral responses: insights from a Cyp2a(4/5)bgs-null mouse.

    Science.gov (United States)

    Li, Lei; Jia, Kunzhi; Zhou, Xin; McCallum, Sarah E; Hough, Lindsay B; Ding, Xinxin

    2013-12-01

    Nicotine metabolism is believed to affect not only nicotine's pharmacological effects but also nicotine addiction. As a key step toward testing this hypothesis, we have studied nicotine metabolism and nicotine's pharmacological and behavioral effects in a novel knockout mouse model [named Cyp2a(4/5)bgs-null] lacking a number of cytochrome P450 genes known to be or possibly involved in nicotine metabolism, including two Cyp2a and all Cyp2b genes. We found that, compared with wild-type mice, the Cyp2a(4/5)bgs-null mice showed >90% decreases in hepatic microsomal nicotine oxidase activity in vitro, and in rates of systemic nicotine clearance in vivo. Further comparisons of nicotine metabolism between Cyp2a(4/5)bgs-null and Cyp2a5-null mice revealed significant roles of both CYP2A5 and CYP2B enzymes in nicotine clearance. Compared with the behavioral responses in wild-type mice, the decreases in nicotine metabolism in the Cyp2a(4/5)bgs-null mice led to prolonged nicotine-induced acute pharmacological effects, in that null mice showed enhanced nicotine hypothermia and antinociception. Furthermore, we found that the Cyp2a(4/5)bgs-null mice developed a preference for nicotine in a conditioned place preference test, a commonly used test of nicotine's rewarding effects, at a nicotine dose that was 4-fold lower than what was required by wild-type mice. Thus, CYP2A/2B-catalyzed nicotine clearance affects nicotine's behavioral response as well as its acute pharmacological effects in mice. This result provides direct experimental support of the findings of pharmacogenetic studies that suggest linkage between rates of nicotine metabolism and smoking behavior in humans.

  10. Effects of nicotine-containing and "nicotine-free" e-cigarette refill liquids on intracranial self-stimulation in rats.

    Science.gov (United States)

    Harris, Andrew C; Muelken, Peter; Smethells, John R; Yershova, Katrina; Stepanov, Irina; Olson, Thao Tran; Kellar, Kenneth J; LeSage, Mark G

    2018-02-01

    Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported that an EC refill liquid produced less aversive/anhedonic effects at a high nicotine dose than nicotine alone as measured by elevations in intracranial self-stimulation (ICSS) thresholds, which may reflect the presence of behaviorally active non-nicotine constituents (e.g., propylene glycol) in the EC liquids. The primary objective of this study was to assess the generality of our prior ICSS findings to two additional EC liquids. We also compared effects of "nicotine-free" varieties of these EC liquids on ICSS, as well as binding affinity and/or functional activity of nicotine alone, nicotine-containing EC liquids, and "nicotine-free" EC liquids at nicotinic acetylcholine receptors (nAChRs). Nicotine alone and nicotine dose-equivalent concentrations of both nicotine-containing EC liquids produced similar lowering of ICSS thresholds at low to moderate nicotine doses, indicating similar reinforcement-enhancing effects. At high nicotine doses, nicotine alone elevated ICSS thresholds (a measure of anhedonia-like behavior) while the EC liquids did not. Nicotine-containing EC liquids did not differ from nicotine alone in terms of binding affinity or functional activity at nAChRs. "Nicotine-free" EC liquids did not affect ICSS, but bound with low affinity at some (e.g., α4ß2) nAChRs. These findings suggest that non-nicotine constituents in these EC liquids do not contribute to their reinforcement-enhancing effects. However, they may attenuate nicotine's acute aversive/anhedonic and/or toxic effects, which may moderate the abuse liability and/or toxicity of ECs. Copyright © 2018. Published by Elsevier B.V.

  11. Greenhouse gas production : a comparison between aerobic and anaerobic wastewater treatment technology

    Energy Technology Data Exchange (ETDEWEB)

    Cakir, F.Y.; Stenstrom, M.K. [Univ. of California at Los Angeles, Los Angles, CA (United States). Dept. of Civil and Environmental Engineering

    2004-07-01

    Human activities in the last 200 years have increased the atmospheric content of greenhouse gases. Wastewater treatment contributes carbon dioxide and methane. Sewage treatment contributes approximately 5 per cent of global methane emissions. In this paper, the authors attempt to estimate greenhouse gas production from domestic wastewater treatment, both aerobic and anaerobic. In anaerobic processes, complex wastes are stabilized in three basic steps: hydrolysis, acid fermentation, and methanogenesis. Anaerobic processes studied include the upflow anaerobic sludge blanket reactor. For low strength wastewater anaerobic processes will produce more greenhouse gases, mainly methane. At higher strengths the aerobic method is more polluting, with the crossover point depending on the relative efficiency of the aerobic system. If the evolved methane can be recovered, the anaerobic system would have less emissions for all strengths. 6 refs., 5 figs.

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

    Science.gov (United States)

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

    2017-05-15

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

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

    Science.gov (United States)

    Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy

    2016-01-01

    Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg−1 base weight) from saline. One group received additional nicotine treatment post‐session (1.78 mg·kg−1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro‐β‐erythroidine did not. Midazolam produced 0% nicotine‐lever responding. The nAChR agonists epibatidine, RTI‐36, cytisine and varenicline produced >96% nicotine‐lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine‐like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Conclusion and Implications Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID:27667659

  14. Robust Escalation of Nicotine Intake with Extended Access to Nicotine Self-Administration and Intermittent Periods of Abstinence

    Science.gov (United States)

    Cohen, Ami; Koob, George F; George, Olivier

    2012-01-01

    Although established smokers have a very regular pattern of smoking behavior, converging lines of evidence suggest that the escalation of smoking behavior is a critical factor in the development of dependence. However, the neurobiological mechanisms that underlie the escalation of smoking are unknown, because there is no animal model of the escalation of nicotine intake. On the basis of the pattern of smoking behavior in humans and presence of monoamine oxidase inhibitors in tobacco smoke, we hypothesized that the escalation of nicotine intake may only occur when animals are given extended-access (21 h per day) self-administration sessions after repeated periods of abstinence (24–48 h), and after chronic inhibition of monoamine oxidase using phenelzine sulfate. Intermittent access (every 24–48 h) to extended nicotine self-administration produced a robust escalation of nicotine intake, associated with increased responding under fixed- and progressive-ratio schedules of reinforcement, and increased somatic signs of withdrawal. The escalation of nicotine intake was not observed in rats with intermittent access to limited (1 h per day) nicotine self-administration or daily access to extended (21 h per day) nicotine self-administration. Moreover, inhibition of monoamine oxidase with daily administration of phenelzine increased nicotine intake by ∼50%. These results demonstrate that the escalation of nicotine intake only occurs in animals given intermittent periods of abstinence with extended access to nicotine, and that inhibition of monoamine oxidase may contribute to the escalation of smoking, thus validating both an animal model of the escalation of smoking behavior and the contribution of monoamine oxidase inhibition to compulsive nicotine-seeking. PMID:22549121

  15. Effect of vitamins on the aerobic degradation of 2-chlorophenol, 4-chlorophenol, and 4-chlorobiphenyl.

    Science.gov (United States)

    Kafkewitz, D; Fava, F; Armenante, P M

    1996-11-01

    The effect of vitamins on the aerobic degradation and dechlorination of 2-chlorophenol and 4-chlorophenol by Pseudomonas pickettii, strain LD1, and 4-chlorobiphenyl by Pseudomonas sp. strain CPE1 was determined. These microorganisms are capable of using the target compounds as the sole carbon and energy source, but do not need vitamins to metabolize them. The addition to the culture medium of a vitamin solution containing biotin, folic acid, pyridoxine hydrochloride, riboflavin, thiamine hydrochloride, niacin, pantothenic acid, cyanocobalamin, p-aminobenzoic acid, and thioctic acid (total final concentration: produced was also detected during the same period, indicating active (and often stoichiometric) dechlorination of the target compounds.

  16. Effect of Nicotine Administration on Estrous Cycle in Female Albino ...

    African Journals Online (AJOL)

    Although it has been emphasized that cigarette smoking is not always synonymous with nicotine administration, the toxic effect of cigarette has often been associated with the nicotine content in cigarette. Cigarette is known to contain toxic, carcinogenic, mutagenic, growth retardative and immunosuppressive compounds.

  17. Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Magata, Yasuhiro; Kitano, Haruhiro; Shiozaki, Toshiki; Iida, Yasuhiko; Nishizawa, Sadahiko; Saji, Hideo; Konishi, Junji

    2000-01-01

    The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3 H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125 I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions

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

    Science.gov (United States)

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

    2017-10-01

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

  19. Pulse radiolysis study on aqueous solution of nicotine

    International Nuclear Information System (INIS)

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

    2004-01-01

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

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

    African Journals Online (AJOL)

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

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

    Directory of Open Access Journals (Sweden)

    Seyed Saadat Seyedeh Nazanin

    2014-03-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

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

    DEFF Research Database (Denmark)

    Bekö, Gabriel; Morrison, Glenn; Weschler, Charles J.

    2017-01-01

    clothing that has previously absorbed/adsorbed indoor air pollutants can increase dermal uptake. A recent experiment demonstrated that dermal uptake of airborne nicotine directly from air or from clothing can occur (Bekö et al., 2017). The current study aims to expand our knowledge on the dermal uptake...... of nicotine, by conducting more extensive experiments....

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

    African Journals Online (AJOL)

    It has been widely established that nicotine , the active pharmacological agent in tobacco has antinociceptive effects , but the mechanism of this activity is yet to be fully investigated . The present study examined the effects of two adrenergic receptor antagonists , propranolol and prazosin .on nicotine antinociception using ...

  7. Construction of an enantiopure bivalent nicotine vaccine using synthetic peptides.

    Directory of Open Access Journals (Sweden)

    David F Zeigler

    Full Text Available Clinical outcomes of anti-nicotine vaccines may be improved through enhancements in serum antibody affinity and concentration. Two strategies were explored to improve vaccine efficacy in outbred mice: the use of enantiopure haptens and formulation of a bivalent vaccine. Vaccines incorporating natural (- nicotine haptens improved relative antibody affinities >10-fold over (+ haptens, stimulated a two-fold boost in nicotine serum binding capacity, and following injection with 3 cigarette equivalents of nicotine, prevented a larger proportion of nicotine (>85% from reaching the brain. The activity of a bivalent vaccine containing (- 3'AmNic and (- 1'SNic haptens was then compared to dose-matched monovalent groups. It was confirmed that antisera generated by these structurally distinct haptens have minimal cross-reactivity and stimulate different B cell populations. Equivalent antibody affinities were detected between the three groups, but the bivalent group showed two-fold higher titers and an additive increase in nicotine serum binding capacity as compared to the monovalent groups. Mice immunized with the bivalent formulation also performed better in a nicotine challenge experiment, and prevented >85% of a nicotine dose equivalent to 12 cigarettes from reaching the brain. Overall, enantiopure conjugate vaccines appear to improve serum antibody affinity, while multivalent formulations increase total antibody concentration. These findings may help improve the performance of future clinical candidate vaccines.

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

    Science.gov (United States)

    Patten, Christi A.

    2000-01-01

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

  9. Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Magata, Yasuhiro E-mail: magata@kuhp.kyoto-u.ac.jp; Kitano, Haruhiro; Shiozaki, Toshiki; Iida, Yasuhiko; Nishizawa, Sadahiko; Saji, Hideo; Konishi, Junji

    2000-01-01

    The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using {sup 3}H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of {sup 125}I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions.

  10. Maternal nicotine exposure during pregnancy and developtnent of ...

    African Journals Online (AJOL)

    The results show that maternal nicotine exposure interferes with elastic tissue formation. It also interferes with alveoli formation and causes the development of emphysema- like lesions. It is therefore suggested that maternal nicotine intake frolll smoking during pregnancy and lactation may interfere with lung developlllent ...

  11. Racial differences in hair nicotine concentrations among smokers.

    Science.gov (United States)

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

    2012-08-01

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

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

    African Journals Online (AJOL)

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

  13. Uncoupled angiogenesis and osteogenesis in nicotine-compromised bone healing.

    Science.gov (United States)

    Ma, Li; Zheng, Li Wu; Sham, Mai Har; Cheung, Lim Kwong

    2010-06-01

    Nicotine is the main chemical component responsible for tobacco addiction. This study aimed to evaluate the influence of nicotine on angiogenesis and osteogenesis and the associated expression of angiogenic and osteogenic mediators during bone healing. Forty-eight adult New Zealand White rabbits were randomly assigned to a nicotine group and a control group. Nicotine pellets (1.5 g, 60-day time release) or placebo pellets were implanted in the neck subcutaneous tissue. The nicotine or placebo exposure time for all the animals was 7 weeks. Unilateral mandibular distraction osteogenesis was performed. Eight animals in each group were euthanized on day 5, day 11 of active distraction, and week 1 of consolidation, respectively. The mandibular samples were subjected to radiographic, histologic, immunohistochemical, and real-time reverse-transcriptase polymerase chain reaction examinations. Nicotine exposure upregulated the expression of hypoxia inducible factor 1alpha and vascular endothelial growth factor and enhanced angiogenesis but inhibited the expression of bone morphogenetic protein 2 and impaired bone healing. The results indicate that nicotine decouples angiogenesis and osteogenesis in this rabbit model of distraction osteogenesis, and the enhanced angiogenesis cannot compensate for the adverse effects of nicotine on bone healing. (c) 2010 American Society for Bone and Mineral Research.

  14. Relation entre la sensibilisation locomotrice à la nicotine et les ...

    African Journals Online (AJOL)

    This study was conducted in parallel with a study of locomotor sensitization to nicotine. It involves taking daily weights of the rats before they register their locomotor activity in circular corridors (cyclotrons) versus time for a period of 2 months. The results are highly significant. From the first there injections, rats nicotinic, ...

  15. Effect of crude garlic extract on nicotine induced hyperglycaemia ...

    African Journals Online (AJOL)

    The effect of curde garlic extract on nicotine induced hyperglycaemia and hyperlipidaemia has been studied in albino rats. Four groups of 6 rats each were used. A control group received saline, a second group received 1mg/kg nicotine i.p., the third group received 305 per kg body weight o acqueous garlic extract orally ...

  16. The effect of potential electronic nicotine delivery system regulations on nicotine product selection.

    Science.gov (United States)

    Pesko, Michael F; Kenkel, Donald S; Wang, Hua; Hughes, Jenna M

    2016-04-01

    To estimate the effect of potential regulations of electronic nicotine delivery systems (ENDS) among adult smokers, including increasing taxes, reducing flavor availability and adding warning labels communicating various levels of risk. We performed a discrete choice experiment (DCE) among a national sample of 1200 adult smokers. We examined heterogeneity in policy responses by age, cigarette quitting interest and current ENDS use. Our experiment overlapped January 2015 by design, providing exogenous variation in cigarette quitting interest from New Year resolutions. KnowledgePanel, an online panel of recruited respondents. A total of 1200 adult smokers from the United States. Hypothetical purchase choice of cigarettes, nicotine replacement therapy and a disposable ENDS. Increasing ENDS prices from $3 to $6 was associated with a 13.6 percentage point reduction in ENDS selection (P taxes, a proposed US Food and Drug Administration warning label for electronic nicotine delivery systems and a more severe warning label may discourage adult smokers from switching to electronic nicotine delivery systems. Reducing the availability of flavors may reduce ENDS use by young adult smokers. © 2015 Society for the Study of Addiction.

  17. Neuronal Nicotinic Acetylcholine Receptors: Neuroplastic Changes underlying Alcohol and Nicotine Addictions

    Directory of Open Access Journals (Sweden)

    Allison Anne Feduccia

    2012-08-01

    Full Text Available Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug’s reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs. The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine’s effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies.

  18. Tachyphylaxis and sensitization to nicotine-induced tachycardiac and pressor effects after nicotine infusions.

    Science.gov (United States)

    Cruz, S L; Vidrio, H

    1997-01-01

    This work examined the effects of nicotine on mean arterial pressure and heart rate in non-anesthetized spinal rats. Nicotine (200 mg/kg) was administered as a single bolus, as infusions lasting 7.5, 15 or 30 min, and as a post-infusion bolus. A nicotine bolus increased pressure and rate. These effects were less marked as the rate of infusion decreased. The infusions affected differentially the effects of a subsequent bolus. Thus, while tachycardia was decreased, the blood pressure rise was increased. An initial transient bradycardia was observed after bolus administration, but not during infusions; this effect was unchanged after post-infusion boluses. Pharmacological analysis indicated that tachycardia and bradycardia were predominantly due to ganglionic stimulation, while adrenal and sympathetic nerve catecholamine release played a major role in the pressor response. These results indicate that slow nicotine infusions do not induce tachyphylaxis for all of the cardiovascular effects of a subsequent bolus, and that development of acute tolerance appears to depend on the mechanism of action of the response.

  19. 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.

  20. Analysis of Escherichia coli nicotinate mononucleotide adenylyltransferase mutants in vivo and in vitro

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    Rydén-Aulin Monica

    2005-09-01

    Full Text Available Abstract Background Adenylation of nicotinate mononucleotide to nicotinate adenine dinucleotide is the penultimate step in NAD+ synthesis. In Escherichia coli, the enzyme nicotinate mononucleotide adenylyltransferase is encoded by the nadD gene. We have earlier made an initial characterization in vivo of two mutant enzymes, NadD72 and NadD74. Strains with either mutation have decreased intracellular levels of NAD+, especially for one of the alleles, nadD72. Results In this study these two mutant proteins have been further characterized together with ten new mutant variants. Of the, in total, twelve mutations four are in a conserved motif in the C-terminus and eight are in the active site. We have tested the activity of the enzymes in vitro and their effect on the growth phenotype in vivo. There is a very good correlation between the two data sets. Conclusion The mutations in the C-terminus did not reveal any function for the conserved motif. On the other hand, our data has lead us to assign amino acid residues His-19, Arg-46 and Asp-109 to the active site. We have also shown that the nadD gene is essential for growth in E. coli.

  1. Alcohol, caffeine, and nicotine consumption in adolescents: hair analysis versus self-report.

    Science.gov (United States)

    Bertol, Elisabetta; Vaiano, Fabio; Boscolo-Berto, Rafael; Fioravanti, Alessia; Palumbo, Diego; Catalani, Valeria; Mari, Francesco; Patussi, Valentino; Serpelloni, Giovanni

    2017-05-01

    Clinical reliability of self-reported data for alcohol, caffeine, and nicotine consumptions is lacking, particularly in adolescents. To compare a self-report questionnaire and hair analysis to assess the reliability and effectiveness of the self-report. A cross-sectional study on 14-15-year-old Italian students (n = 874, 38% males, 62% females) was performed comparing self-reported data to hair analysis. The latter quantified hair concentrations of caffeine, nicotine, cotinine, ethyl glucuronide (EtG), and fatty acid ethyl esters (FAEEs) using mass spectrometry. Concordance between self-report and hair testing ranged from good to poor across substances and levels of use: poor for heavy alcohol intake (EtG: k = 0.36, 20 positive cases by hair analysis, false negative by self-report, 2.3% of total sample; FAEE k = 0.31, 25 positive cases, 2.9% of total sample); fair to poor for active smokers (k = 0.40, 125 positive cases, 14.3% of total sample); and moderate for caffeine (k = 0.57, 56 positive cases, 6.4% of total sample). Epidemiological studies on alcohol, caffeine, and nicotine consumption in adolescents may benefit from the inclusion of toxicological analysis on hair samples to overcome the under-reporting phenomenon of questionnaires and detect more cases of problematic substance use.

  2. Saturation solubility of nicotine, scopolamine and paracetamol in model stratum corneum lipid matrices.

    Science.gov (United States)

    Mundstock, Anne; Lee, Geoffrey

    2014-10-01

    The saturation solubilities of nicotine and scopolamine bases as well as acidic paracetamol were measured in two different model stratum corneum lipid matrices. Light microscopy visualized the presence of drug above its solubility either as droplets or crystalline particles. Neither wide-angle X-ray diffraction nor DSC detected the drugs. The saturation solubilities of the nicotine and scopolamine bases are 3-5% w/w and 5-10% w/w respectively. Paracetamol strongly disrupts the lamellar phase formed by the lipids and could be dissolved to >20% w/w. Based on these results the saturation solubilities of nicotine and scopolamine in an intact stratum corneum membrane are estimated to be up to 17.5 μg and 35 μg drug per milligrams of stratum corneum membrane respectively. These concentrations are well above values obtained by tape stripping of intact stratum corneum during a permeation experiment. The drug's saturation solubility in the stratum corneum's lipid phase is therefore unlikely to be rate-limiting for permeation of these two drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Spectroscopic characterization of organic matter of a soil and vinasse mixture during aerobic or anaerobic incubation.

    Science.gov (United States)

    Doelsch, Emmanuel; Masion, Armand; Cazevieille, Patrick; Condom, Nicolas

    2009-06-01

    Mineralization potentials are often used to classify organic wastes. These methods involve measuring CO(2) production during batch experiments, so variations in chemical compounds are not addressed. Moreover, the physicochemical conditions are not monitored during the reactions. The present study was designed to address these deficiencies. Incubations of a mixture of soil and waste (vinasse at 20% dry matter from a fermentation industry) were conducted in aerobic and anaerobic conditions, and liquid samples obtained by centrifugation were collected at 2h, 1d and 28 d. Dissolved organic carbon (DOC) patterns highlighted that: there was a "soil effect" which increased organic matter (OM) degradation in all conditions compared to vinasse incubated alone; and OM degradation was faster under aerobic conditions since 500 mgkg(-1) of C remained after aerobic incubation, as compared to 4000 mgkg(-1) at the end of the anaerobic incubation period. No changes were detected by Fourier transform infrared spectroscopy (FTIR) between 2h and 1d incubation. At 28 days incubation, the FTIR signal of the aerobic samples was deeply modified, thus confirming the high OM degradation. Under anaerobic conditions, the main polysaccharide contributions (nu(C-O)) disappeared at 1000 and 1200 cm(-1), as also confirmed by the (13)C NMR findings. Under aerobic incubation, a 50% decrease in the polysaccharide proportion was observed. Under anaerobic conditions, significant chemical modifications of the organic fraction were detected, namely formation of low molecular weight organic acids.

  4. Isolation and characterization of medically important aerobic actinomycetes in soil of iran (2006 - 2007).

    Science.gov (United States)

    Aghamirian, Mohammad Reza; Ghiasian, Seyed Amir

    2009-01-01

    The aerobic actinomycetes are a large group of soil-inhabiting bacteria that occur worldwide. Some of them are the main cause of two important diseases, nocardiosis and actinomycetoma. To identify the prevalence and geographic distribution of aerobic actinomycetes in soil of Qazvin province, a study was carried out during 2006-2007. In this study, the incidence and diversity of medically important aerobic actinomycetes was determined in 300 soil samples of different parts of Qazvin. The suspensions of superficial soil samples were prepared by adding of normal saline, streptomycin and chloramphenicol and the supernatants were cultured on brain-heart infusion agar and Sabouraud's dextrose agar contain cycloheximide. The isolated microorganisms were examined by Gram and acid-fast stains and were identified biochemically and morphologically. Of 96 aerobic actinomycetes isolates identified, Actinomadura madurae and Streptomyces somaliensis were the most frequently isolated species each representing 19.8% of isolates, followed by Nocardia asteroides (15.6%), N. otitidiscaviarum (9.4%), N. brasiliensis (7.3%), A. peletieri, S. griseus, and Nocardia spp. (each 5.2%), and N. transvalensis, Nocardiopsis dassonvillei, Actinomadura spp. and Streptomyces spp. (each 3.1%). To the best of our knowledge, this is the first report on epidemiological investigation of medically important aerobic actinomycetes in soil samples from Iran. In recent years, mycetoma and nocardiosis have been increasingly reported in Iran. The results showed that medically important actinomycetes occur in the environment of Iran and soil could be potential source of actinomycotic infections.

  5. Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome

    International Nuclear Information System (INIS)

    Yokota, Takashi; Kinugawa, Shintaro; Okita, Koichi

    2011-01-01

    Lower aerobic capacity is a strong and independent predictor of cardiovascular morbidity and mortality in patients with metabolic syndrome (MetS). However, the mechanisms are not fully elucidated. We tested the hypothesis that skeletal muscle dysfunction could contribute to the lower aerobic capacity in MetS patients. The incremental exercise tests with cycle ergometer were performed in 12 male patients with MetS with no habitual exercise and 11 age-, sex- and activity-matched control subjects to assess the aerobic capacity. We performed 31 phosphorus-magnetic resonance spectroscopy (MRS) to assess the high-energy phosphate metabolism in skeletal muscle during aerobic exercise. Proton-MRS was also performed to measure intramyocellular lipid (IMCL) content. Peak oxygen uptake (peak VO 2 ; 34.1±6.2 vs. 41.4±8.4 ml kg -1 min -1 , P -1 min -1 , P 2 (r=-0.64) and AT (r=-0.60), respectively. IMCL content was threefold higher in MetS and was inversely correlated with peak VO 2 (r=-0.47) and AT (r=-0.52), respectively. Moreover, there was a positive correlation between IMCL content and PCr loss (r=0.64). These results suggested that lean-body aerobic capacity in MetS patients was lower compared with activity-matched healthy subjects, which might be due to the reduced intramuscular fatty acid oxidative metabolism. (author)

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

    Directory of Open Access Journals (Sweden)

    Anastasia Moysidou

    2016-05-01

    Full Text Available Introduction. The purpose of this study was to evaluate the knowledge and perceptions of Greek healthcare professionals about nicotine, nicotine replacement therapies and electronic cigarettes. Methods. An online survey was performed, in which physicians and nurses working in private and public healthcare sectors in Athens-Greece were asked to participate through email invitations. A knowledge score was calculated by scoring the correct answers to specific questions with 1 point. Results. A total of 262 healthcare professionals were included to the analysis. Most had daily contact with smokers in their working environment. About half of them considered that nicotine has an extremely or very important contribution to smoking-related disease. More than 30% considered nicotine replacement therapies equally or more addictive than smoking, 76.7% overestimated their smoking cessation efficacy and only 21.0% would recommend them as long-term smoking substitutes. For electronic cigarettes, 45.0% considered them equally or more addictive than smoking and 24.4% equally or more harmful than tobacco cigarettes. Additionally, 35.5% thought they involve combustion while the majority responded that nicotine in electronic cigarettes is synthetically produced. Only 14.5% knew about the pending European regulation, but 33.2% have recommended them to smokers in the past. Still, more than 40% would not recommend electronic cigarettes to smokers unwilling or unable to quit smoking with currently approved medications. Cardiologists and respiratory physicians, who are responsible for smoking cessation therapy in Greece, were even more reluctant to recommend electronic cigarettes to this subpopulation of smokers compared to all other participants. The knowledge score of the whole study sample was 7.7 (SD: 2.4 out of a maximum score of 16. Higher score was associated with specific physician specialties. Conclusions. Greek healthcare professionals appear to overestimate

  7. Aerobic vaginitis: no longer a stranger.

    Science.gov (United States)

    Donders, Gilbert G G; Bellen, Gert; Grinceviciene, Svitrigaile; Ruban, Kateryna; Vieira-Baptista, Pedro

    Aerobic vaginitis (AV) is the name given in 2002 to a vaginal infectious entity which was not recognized as such before. It is characterized by abnormal (dysbiotic) vaginal microflora containing aerobic, enteric bacteria, variable levels of vaginal inflammation and deficient epithelial maturation. Although AV and bacterial vaginosis (BV) share some characteristics, such as a diminished number or absence of lactobacilli, increased discharge (fishy smelling in BV, while in severe forms of AV, a foul, rather rotten smell may be present) and increased pH (often more pronounced in AV), there are also striking differences between the two. There is no inflammation in women with BV, whereas the vagina of women with AV often appears red and edematous, and may even display small erosions or ulcerations. The color of the discharge in BV is usually whitish or gray and of a watery consistency, whereas in AV it is yellow to green and rather thick and mucoid. Women with BV do not have dyspareunia, while some women with severe AV do. Finally, the microscopic appearance differs in various aspects, such as the presence of leucocytes and parabasal or immature epithelial cells in AV and the absence of the granular aspect of the microflora, typical of BV. Despite all these differences, the distinction between AV and BV was not recognized in many former studies, leading to incomplete and imprecise diagnostic workouts and erroneous management of patients in both clinical and research settings. The prevalence of AV ranges between 7 and 12%, and is therefore less prevalent than BV. Although still largely undiagnosed, many researchers and clinicians increasingly take it into account as a cause of symptomatic vaginitis. AV can co-occur with other entities, such as BV and candidiasis. It can be associated with dyspareunia, sexually transmitted infections (such as human papilloma virus, human immunodeficiency virus, Trichomonas vaginalis and Chlamydia trachomatis), chorioamnionitis, fetal

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

    Science.gov (United States)

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

    2018-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  10. Antifungal activity of nicotine and its cobalt complex

    International Nuclear Information System (INIS)

    Zaidi, M.I.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Co(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activity against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cobalt(II) chloride was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine had antifungal activity against all species of fungi studied except Candida albicans, Microsporum canis, Epidermophyton floccosum, Candida tropicalis, and Alternaria infectoria. Cobalt(II) nicotine was found to be effective against all selected species of fungi but ineffective against Candida solani, Penicillium notalum, Microsporum canis, Fusarium solani and Fusarium moniliforme. (author)

  11. The impact of nicotine on bone healing and osseointegration

    DEFF Research Database (Denmark)

    Balatsouka, Dimitra; Gotfredsen, Klaus; Lindh, Christian H

    2005-01-01

    OBJECTIVES: To examine the short-term effect of nicotine on bone healing and osseointegration. MATERIAL AND METHODS: Sixteen female rabbits were divided into two groups. The test group was exposed to nicotine tartrate for 8 weeks and the control group was exposed to placebo. Nicotine or placebo...... was administered via a miniosmotic pump and plasma cotinine levels were measured weekly. The pump delivered 15 mg of nicotine/day for the animals in the test group. All rabbits had three tibial bone preparations. In the proximal and distal bone bed, implants were placed after 4 weeks (right tibia) and after 6...... and the control group. CONCLUSION: Nicotine exposure in a short period of time did not have a significant impact on bone healing or implant osseointegration in rabbits....

  12. Nicotinic mechanisms influencing synaptic plasticity in the hippocampus

    Science.gov (United States)

    Placzek, Andon Nicholas; Zhang, Tao A; Dani, John Anthony

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the hippocampus, and nicotinic signaling plays an important role in neuronal function. In the context of learning and memory related behaviors associated with hippocampal function, a potentially significant feature of nAChR activity is the impact it has on synaptic plasticity. Synaptic plasticity in hippocampal neurons has long been considered a contributing cellular mechanism of learning and memory. These same kinds of cellular mechanisms are a factor in the development of nicotine addiction. Nicotinic signaling has been demonstrated by in vitro studies to affect synaptic plasticity in hippocampal neurons via multiple steps, and the signaling has also been shown to evoke synaptic plasticity in vivo. This review focuses on the nAChRs subtypes that contribute to hippocampal synaptic plasticity at the cellular and circuit level. It also considers nicotinic influences over long-term changes in the hippocampus that may contribute to addiction. PMID:19434057

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

    Directory of Open Access Journals (Sweden)

    Herman S. Cheung

    2016-07-01

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

  14. Historical and current perspective on tobacco use and nicotine addiction.

    Science.gov (United States)

    Dani, John A; Balfour, David J K

    2011-07-01

    Although the addictive influence of tobacco was recognized very early, the modern concepts of nicotine addiction have relied on knowledge of cholinergic neurotransmission and nicotinic acetylcholine receptors (nAChRs). The discovery of the 'receptive substance' by Langley, that would turn out to be nAChRs, and 'Vagusstoff' (acetylcholine) by Loewi, coincided with an exciting time when the concept of chemical synaptic transmission was being formulated. More recently, the application of more powerful techniques and the study of animal models that replicate key features of nicotine dependence have led to important advancements in our understanding of molecular, cellular and systems mechanisms of nicotine addiction. In this review, we present a historical perspective and overview of the research that has led to our present understanding of nicotine addiction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Physiological functions of pyruvate:NADP+oxidoreductase and 2-oxoglutarate decarboxylase in Euglena gracilis under aerobic and anaerobic conditions.

    Science.gov (United States)

    Nakazawa, Masami; Hayashi, Ryuta; Takenaka, Shigeo; Inui, Hiroshi; Ishikawa, Takahiro; Ueda, Mitsuhiro; Sakamoto, Tatsuji; Nakano, Yoshihisa; Miyatake, Kazutaka

    2017-07-01

    In Euglena gracilis, pyruvate:NADP + oxidoreductase, in addition to the pyruvate dehydrogenase complex, functions for the oxidative decarboxylation of pyruvate in the mitochondria. Furthermore, the 2-oxoglutarate dehydrogenase complex is absent, and instead 2-oxoglutarate decarboxylase is found in the mitochondria. To elucidate the central carbon and energy metabolisms in Euglena under aerobic and anaerobic conditions, physiological significances of these enzymes involved in 2-oxoacid metabolism were examined by gene silencing experiments. The pyruvate dehydrogenase complex was indispensable for aerobic cell growth in a glucose medium, although its activity was less than 1% of that of pyruvate:NADP + oxidoreductase. In contrast, pyruvate:NADP + oxidoreductase was only involved in the anaerobic energy metabolism (wax ester fermentation). Aerobic cell growth was almost completely suppressed when the 2-oxoglutarate decarboxylase gene was silenced, suggesting that the tricarboxylic acid cycle is modified in Euglena and 2-oxoglutarate decarboxylase takes the place of the 2-oxoglutarate dehydrogenase complex in the aerobic respiratory metabolism.

  16. Septal innervation regulates the function of alpha7 nicotinic receptors in CA1 hippocampal interneurons.

    Science.gov (United States)

    Thinschmidt, Jeffrey S; Frazier, Charles J; King, Michael A; Meyer, Edwin M; Papke, Roger L

    2005-10-01

    The hippocampus receives substantial input from the medial septum/diagonal band of broca (MS/DB) via the fibria-fornix (FF). Projections from the MS/DB innervate hippocampal interneurons that express alpha7 nicotinic receptors and regulate excitation in principal cell populations. In the present report we used stereotaxic surgery, whole-cell patch clamping, and immunohistochemical techniques to evaluate the effects of FF and MS/DB lesions on alpha7 nicotinic receptors in stratum radiatum interneurons. Focal somatic application of ACh (1 mM) evoked methyllycaconitine (MLA)-sensitive currents that were markedly reduced following aspirative lesions of the FF. Reductions in current amplitudes were prevented or restored to levels not significantly different from controls following in vivo treatment with the alpha7-selective agonist GTS-21, and GTS-21 treatment did not change current amplitudes measured in tissue from unlesioned animals. MS/DB injections of the selective cholinergic neurotoxin 192 IgG-saporin did not affect alpha7 receptor currents, although MS/DB ChAT and hippocampal AChE immunolabeling were significantly reduced. In contrast, kainic acid lesions of the MS/DB, potentially more selective for GABAergic projection neurons, produced significant reductions in current amplitudes. These findings are the first to show functional changes in alpha7 receptors following hippocampal denervation and suggest that MS/DB hippocampal innervation regulates functional aspects of hippocampal alpha7 receptors. The results confirm hippocampal alpha7 nicotinic receptors as viable therapeutic targets in diseases that involve degradation of the septohippocampal pathway and may indicate that GABAergic MS/DB hippocampal input plays a more substantial role in the regulation of alpha7 nicotinic receptor function than MS/DB hippocampal cholinergic input.

  17. Incorporation of Nicotine into Silicone Coatings for Marine Applications

    Science.gov (United States)

    Jaramillo, Sandy Tuyet

    PDMS-based marine coatings presently used are limited by their inability to mitigate microfouling which limits their application to high speed vessels. PDMS coatings are favored when viable, due to their foul release properties of macrofouling organisms. Natural products have been investigated for antifouling properties for potential use in these marine antifouling coatings but few have incorporated natural products into coatings or coating systems. The purpose of the research was to establish the corrosion inhibiting properties of nicotine and to incorporate nicotine, a biodegradable and readily available natural product, into a PDMS coating to demonstrate the use of a natural product in a coating for marine applications. The corrosion inhibiting properties of nicotine was examined using potentiodynamic polarization scans, material characterization techniques such as scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction, quartz crystal microbalance and electrochemical impedance spectroscopy. Nicotine was determined to be an anodic corrosion inhibitor for mild steel immersed in simulated seawater with the ability to precipitate a protective calcium carbonate film. Electrochemical impedance spectroscopy was used to evaluate the performance of the developed nicotine incorporated coatings on mild steel immersed in simulated seawater over 21 days of immersion. The coatings with 2 wt.% of nicotine incorporated in the coating with a ratio of 1:30 of additional platinum catalyst to nicotine exhibited the best performance for intact coatings. This coating had the most favorable balance of the amount of nicotine and platinum catalyst of all the coatings evaluated. Overall, all nicotine incorporated coatings had a performance improvement when compared to the control PDMS coating. Of the nicotine incorporated coatings that were tested with an artificial pin-hole defect, the 2PDMS coating also exhibited the best performance with significant

  18. Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

    Science.gov (United States)

    Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

    2017-06-01

    Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p nicotine dependence (p Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and

  19. 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.

  20. Nicotine effects on general semantic priming in Parkinson's disease.

    Science.gov (United States)

    Holmes, Anna D; Copland, David A; Silburn, Peter A; Chenery, Helen J

    2011-06-01

    In young healthy nonsmokers, effects of nicotine on semantic processing have been observed under strategy-based priming procedures but not under more general priming procedures (Holmes, Chenery, & Copland, 2008; Holmes, Chenery, & Copland, 2010). Effects of nicotine under general priming procedures, however, may be mediated by baseline priming levels that are below optimum such as when compromised by disease. Nicotinic mechanisms may be involved in the cognitive sequalae of Parkinson's disease (PD). Evidence suggests that semantic processing may be compromised in PD but the potential benefit of nicotinic stimulation is unknown. This study investigated the effects of nicotine on semantic processing in nonsmokers with PD (n = 12) and nonsmoking matched controls (n = 17) using general priming procedures. Specifically, an automatic priming task (0.15 relatedness proportion, RP, and 200 ms stimulus onset asynchrony, SOA) and a controlled priming task (0.8 RP and 1000 ms SOA) were used. Prime-target category relation (category related, noncategory related) was also manipulated. Transdermal nicotine patches (7 mg/24 h) were administered in a double-blind, placebo-controlled, crossover design. For the automatic task, nicotine did not influence priming effects for PD. Unexpectedly, compromised automatic priming for controls was ameliorated. For the controlled task, nicotine influenced priming effects for PD but not controls. The patterns of priming and nicotine effects across the tasks suggest an age-related slowing of the rate of semantic activation for controls, which may be exacerbated in PD. Overall, the findings indicate that nicotine can improve compromised semantic processing in PD, and also influence semantic processing in healthy older individuals. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  1. 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.

  2. Does Aerobic Exercise Influence Intrinsic Brain Activity?

    DEFF Research Database (Denmark)

    Flodin, Pär; Jonasson, Lars S; Riklund, Katrin

    2017-01-01

    Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64-78 years) were randomized into either an aerobic...... exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling...... group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings...

  3. Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits

    NARCIS (Netherlands)

    Mansvelder, H.D.; Mertz, M.; Role, L.W.

    2009-01-01

    Nicotine is the principle addictive agent delivered via cigarette smoking. The addictive activity of nicotine is due to potent interactions with nicotinic acetylcholine receptors (nAChRs) on neurons in the reinforcement and reward circuits of the brain. Beyond its addictive actions, nicotine is

  4. Repeated Administration of the GABA\\(_B\\) Receptor Positive Modulator BHF177 Decreased Nicotine Self-Administration, and Acute Administration Decreased Cue-Induced Reinstatement of Nicotine Seeking in Rats

    OpenAIRE

    Vlachou, Styliani; Guery, Sebastien; Froestl, Wolfgang; Benedict, Jessica; Finn, M. G.; Markou, Athina; Banerjee, Deboshri

    2011-01-01

    Abstract: Rationale \\(\\gamma\\)-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA\\(_B\\) receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA\\(_B\\) receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with...

  5. Activity-related behaviors in the hole-board predict nicotine consumption in C57B6 mice perinatally exposed to nicotine.

    Science.gov (United States)

    Gyekis, Joseph; Foreman, Jennifer E; Anthony, Kate; Klein, Laura Cousino; Vandenbergh, David J

    2010-01-05

    Hole-board behaviors of adolescent C57B/6 mice that had been exposed to nicotine during gestation and suckling were evaluated on postnatal days 34-36. Rearing on all three trials significantly predicted higher nicotine intake on a two-bottle choice test administered from days 37-42. For head pokes, there was a weak trend for lower head poking in the first trial to be predictive of higher nicotine intake. Locomotor activity only predicted higher nicotine consumption on the third trial. These results show that hole-board behaviors predict subsequent nicotine intake in mice exposed to nicotine perinatally, especially after habituation to the apparatus.

  6. Therapeutic aspects of aerobic dance participation.

    Science.gov (United States)

    Estivill, M

    1995-01-01

    An ethnographic analysis of aerobic dance exercise culture was conducted to determine the impact of the culture on the mind-body connection. After a review of the predominant theories on the relationship between vigorous exercise and elevated mood, aerobic dance participants' experiences are reported to illustrate how cognitive experience and self-esteem may be influenced. Interviews revealed that some participants achieved a pleasantly altered state of consciousness and respite from depression and stress. The relationship of the work ethic to achievement of participant satisfaction is underscored.

  7. Permissive nicotine regulation as a complement to traditional tobacco control

    Directory of Open Access Journals (Sweden)

    Sumner Walton

    2005-02-01

    Full Text Available Abstract Background Cigarette smoking takes a staggering toll on human health and attracts considerable public health attention, yet real solutions seem distant. The 2004 Family Smoking Prevention and Tobacco Control Act (US Senate bill S2461 would have given the US Food and Drug Administration limited authority to regulate cigarettes to "protect the public health." However, such legislation is unlikely to substantially reduce smoking or related deaths. Discussion The past 500 years of tobacco control efforts demonstrate that nicotine prohibition is a practical impossibility for numerous reasons, state revenue being one of the most ominous. The FDA already has regulatory authority over pharmaceutical grade nicotine products, and requires pharmacists to dispense the most addictive of these only with prescriptions. Meanwhile, every corner store can sell far more addictive and dangerous cigarettes to any adult. The FDA could immediately increase competition between cigarettes and clean nicotine products by approving available nicotine products for over-the-counter sales to adults. Similarly permissive regulation of cigarettes and addictive nicotine products will reduce tobacco use and improve smokers' health, but increase nicotine use in the population. Fortunately, restricted youth access and accurate labeling of nicotine's absolute risks will dissuade many non-smokers from experimenting with it, while accurate depiction of its risks relative to cigarette smoking will encourage many smokers to switch. The FDA could take a series of small steps that might ultimately replace a large proportion of cigarette smoking with equally addictive nicotine products, without risking serious public health setbacks. Vaccine, methadone, and injury prevention policies establish relevant public health precedents. Summary Cigarettes, or an equally addictive alternative, will be a permanent and common product in most societies. Regulations restricting only the safest

  8. Endogenous ACh suppresses LTD induction and nicotine relieves the suppression via different nicotinic ACh receptor subtypes in the mouse hippocampus.

    Science.gov (United States)

    Nakauchi, Sakura; Sumikawa, Katumi

    2014-08-28

    Studying the normal role of nicotinic cholinergic systems in hippocampal synaptic plasticity is critical for understanding how cholinergic loss in Alzheimer's disease (AD) and tobacco use affect cognitive function. However, it is largely unknown how nicotinic cholinergic systems regulate the induction of long-term depression (LTD). Extracellular field potential recordings were performed in hippocampal slices prepared from wild-type, α2, α7, and β2 knockout (KO) mice. Effects of nicotine and nicotinic antagonists on LTD induction in wild-type, α2, α7, and β2 KO mice were compared. Activation of α7 nicotinic acetylcholine receptors (nAChRs) occurs during LTD-inducing stimulation to suppress LTD induction at CA3-CA1 synapses. Nicotine relieves this suppression, causing larger LTD. This nicotine effect was mediated by the activation of non-α7 nAChR subtypes, which were not activated by ACh released during LTD-inducing stimulation, and requires the presence of endogenous ACh-induced α7 nAChR activation. Furthermore, the effect of nicotine was prevented in the presence of mecamylamine, but not dihydro-β-erythroidine, and was still observed in both α2 KO and β2 KO mice. This is the first report to evaluate the involvement of different nAChR subtypes in LTD induction. Findings indicate the involvement of unique non-α7 nAChR subtypes, which have not been considered in the nicotinic modulation of hippocampal long-term potentiation, in the control of LTD induction. The implication of our results is that the loss of cholinergic projections to the hippocampus, which reduces ACh release as seen in AD patients, and nicotine from tobacco smoking can differentially affect LTD induction. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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.

  10. Behavioral effects of nicotine exposure from secondhand tobacco smoke among bar and restaurant workers.

    Science.gov (United States)

    Okoli, Chizimuzo T C; Rayens, Mary Kay; Hahn, Ellen J

    2007-09-01

    This study explores the behavioral effects of nicotine exposure from secondhand tobacco smoke (SHS) on bar and restaurant workers. Baseline data were obtained from a longitudinal study of 105 bar and restaurant workers. Hair nicotine, self-reported SHS exposure, smoking status, symptoms of nicotine exposure after being exposed to a smoky environment, and nicotine dependence were assessed. Nonsmokers reporting four or more symptoms of nicotine exposure had higher hair nicotine levels than those reporting less than four symptoms. Nonsmokers with higher hair nicotine levels were 2.2 times more likely to report 4 or more behavioral symptoms. Self-reported secondhand tobacco smoke exposure and hair nicotine were not predictive of nicotine dependence among smokers. Nicotine exposure from secondhand tobacco smoke may have important behavioral outcomes in nonsmokers. This study provides further evidence for the importance of prohibiting smoking in hospitality venues to protect the health of workers.

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

    Science.gov (United States)

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

    2013-12-01

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

  12. Adaptation to Aerobic Environment of Lactobacillus johnsonii/gasseri Strains

    Directory of Open Access Journals (Sweden)

    Diamante Maresca

    2018-02-01

    Full Text Available Oxygen is considered one of the main factors affecting probiotic bacteria survival due to the induction of oxidative damages caused by the action of reactive oxygen species (ROS. It has been shown that oxidative stress resistance in lactic acid bacteria is strongly dependent on the type of cell metabolism. Shift from fermentative to respiratory metabolism (through the addition of heme and menaquinone and in presence of oxygen was associated to increase in biomass, long-term survival, and production of antioxidant enzymes. The aim of this work was to investigate the effect of