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Scientific Reports Sep 2018Tobacco smoking is the major cause of many chronic diseases, especially lung cancer. Knowledge about population-wide tobacco use and exposure is essential to...
Levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in raw wastewater as an innovative perspective for investigating population-wide exposure to third-hand smoke.
Tobacco smoking is the major cause of many chronic diseases, especially lung cancer. Knowledge about population-wide tobacco use and exposure is essential to characterise its burden on public health and evaluate policy efficacy. Obtaining such knowledge remains challenging with current methods (e.g., surveys, biomonitoring) but can be achievable with wastewater analysis, a promising tool of retrieving epidemiology information. This study examined population-wide exposure to tobacco toxicants and carcinogens through wastewater analysis and explored relationships among these chemicals. Cotinine, trans-3'-hydroxycotinine, anabasine, anatabine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were analysed in samples from Greece, Switzerland and Belgium, where tobacco control policies are different. Measured per-capita mass loads were ranked as: nicotine biomarkers ≫ tobacco markers > carcinogens. Relationships between nicotine biomarkers and tobacco markers implied substantial use of non-tobacco nicotine items besides tobacco products. Geographic profiles of tobacco markers revealed higher levels in Geneva and Athens than Geraardsbergen and Ninove. Environmental third-hand smoke led to NNK detection, with elevated levels observed in Athens where indoor smoking is widespread, posing potential health risks to the population. Our novel outcomes are relevant for public health authorities as they provide indications about external exposure and can thus be used to plan and evaluate tobacco control policies.
Topics: Alkaloids; Anabasine; Belgium; Carcinogens; Cotinine; Greece; Humans; Nitrosamines; Public Health; Pyridines; Switzerland; Tobacco Products; Tobacco Smoke Pollution; Wastewater
PubMed: 30185880
DOI: 10.1038/s41598-018-31324-6 -
Contemporary Clinical Trials Aug 2018Tobacco use and tobacco-related diseases disproportionately affect Alaska Native (AN) people. Using telemedicine, this study aims to identify culturally-tailored,...
The Healing and Empowering Alaskan Lives Toward Healthy-Hearts (HEALTHH) Project: Study protocol for a randomized controlled trial of an intervention for tobacco use and other cardiovascular risk behaviors for Alaska Native People.
BACKGROUND
Tobacco use and tobacco-related diseases disproportionately affect Alaska Native (AN) people. Using telemedicine, this study aims to identify culturally-tailored, theoretically-driven, efficacious interventions for tobacco use and other cardiovascular disease (CVD) risk behaviors among AN people in remote areas.
DESIGN
Randomized clinical trial with two intervention arms: 1) tobacco and physical activity; 2) medication adherence and a heart-healthy AN diet.
PARTICIPANTS
Participants are N = 300 AN men and women current smokers with high blood pressure or high cholesterol.
INTERVENTIONS
All participants receive motivational, stage-tailored, telemedicine-delivered counseling sessions at baseline and 3, 6, and 12 months follow-up; an individualized behavior change plan that is updated at each contact; and a behavior change manual. In Group 1, the focus is on tobacco and physical activity; a pedometer is provided and nicotine replacement therapy is offered. In Group 2, the focus is on medication adherence for treating hypertension and/or hypercholesterolemia; a medication bag and traditional food guide are provided.
MEASUREMENTS
With assessments at baseline, 3, 6, 12, and 18 months, the primary outcome is smoking status, assessed as 7-day point prevalence abstinence, biochemically verified with urine anabasine. Secondary outcomes include physical activity, blood pressure and cholesterol, medication compliance, diet, multiple risk behavior change indices, and cost-effectiveness.
COMMENTS
The current study has the potential to identify novel, feasible, acceptable, and efficacious interventions for treating the co-occurrence of CVD risk factors in AN people. Findings may inform personalized treatment and the development of effective and cost-effective intervention strategies for use in remote indigenous communities more broadly. Clinical Trial Registration # NCT02137902.
Topics: Adult; Alaska Natives; Behavior Control; Cardiovascular Agents; Cardiovascular Diseases; Distance Counseling; Exercise; Female; Humans; Male; Medication Adherence; Quality of Life; Risk Factors; Risk Reduction Behavior; Smoking Cessation; Telemedicine; Tobacco Use Disorder; Randomized Controlled Trials as Topic
PubMed: 29864548
DOI: 10.1016/j.cct.2018.06.003 -
Nature Chemistry Feb 2018Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an...
Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an attractive strategy for preparing valuable functionalized amines from their readily available parent heterocycles, this approach has largely been limited to substrates that require protection of the amine nitrogen atom. In addition, most methods rely on transition metals and are incompatible with the presence of amine N-H bonds. Here we introduce a protecting-group-free approach for the α-functionalization of cyclic secondary amines. An operationally simple one-pot procedure generates products via a process that involves intermolecular hydride transfer to generate an imine intermediate that is subsequently captured by a nucleophile, such as an alkyl or aryl lithium compound. Reactions are regioselective and stereospecific and enable the rapid preparation of bioactive amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.
Topics: Alkaloids; Amines; Anabasine; Chemistry Techniques, Synthetic; Molecular Structure; Stereoisomerism
PubMed: 29359746
DOI: 10.1038/nchem.2871 -
Heliyon Nov 2017A range of endemic species are chewed as a smokeless tobacco by several Aboriginal populations of Australia. In tobacco research, nicotine to nornicotine conversion is...
A range of endemic species are chewed as a smokeless tobacco by several Aboriginal populations of Australia. In tobacco research, nicotine to nornicotine conversion is important because nornicotine lowers tobacco quality and is detrimental to health. A diverse group of cytochrome P450 genes with different transcriptional regulations are involved in this conversion. The primary aims of this study were to quantify the pyridine alkaloids and investigate nicotine to nornicotine conversion in laboratory-grown Australian spp. Nicotine, nornicotine, anatabine, anabasine, myosmine and cotinine were quantified in fresh leaves of 24 out of the 26 recognised Australian taxa. Conserved regions of CYP82E related genes were PCR amplified in all studied taxa. The conversion process in fresh leaves was compared with that in leaves that underwent a simulated curing process for species that we identified as being high converters (, ) and low converters (). Agarose gel electrophoretic analysis of CYP82E related genes obtained from the PCR amplification of the cDNA in fresh versus leaves with simulated curing showed about a 3-fold increase in transcript accumulation levels in cured leaves of the high converter species, while the transcript accumulation in and maintained a steady basal level and increased by a small amount in . This suggests the presence of functional loci that are triggered by curing in only high converter species and indicates a potential risk for chewers of high converter species.
PubMed: 29264422
DOI: 10.1016/j.heliyon.2017.e00469 -
Pharmacology, Biochemistry, and Behavior Feb 2018The ability of smoking to reduce body weight serves as motivation for continued smoking. It is unclear to what extent non-nicotine constituents in cigarettes are...
The ability of smoking to reduce body weight serves as motivation for continued smoking. It is unclear to what extent non-nicotine constituents in cigarettes are contributing to the weight-reducing effect of smoking. The purpose of the current study was to examine the effects of nicotine and four minor tobacco alkaloids (nornicotine, cotinine, anatabine, and anabasine) on food intake, one of the key regulators of body weight. In addition, a smokeless tobacco extract (STE) and e-cigarette (EC) refill liquid were used to model the effects of actual tobacco product exposure on food intake. Male Holztman rats were trained to lever press for food pellets during daily 2h sessions in operant chambers. In Experiment 1, the effects of subcutaneous injections of saline, nicotine (0.25-1.00mg/kg), nornicotine (0.50-6.00mg/kg), cotinine (1.00-100.00mg/kg), anatabine (0.25-3.00mg/kg), and anabasine (0.50-4.00mg/kg) were assessed. In Experiment 2, rats from Experiment 1 were used to examine the effects of nicotine, STE, and EC liquid. All alkaloids, except cotinine, produced a dose-dependent reduction in overall food intake. The highest doses of all drugs significantly reduced latency and response rate to obtain the first pellet. At some doses, nicotine, anatabine, and nornicotine reduced food intake within the first 45min without compensatory increases in intake later in the session. STE and EC liquid produced dose dependent decreases in food intake similar to nicotine alone. These data suggest that minor tobacco alkaloids have appetite suppressant effects and warrant further investigation into their effects on body weight, energy intake, and energy expenditure under free-feeding conditions. However, findings with STE and EC liquid suggest that nicotine is the primary constituent in these products to affect food intake, whereas levels of minor alkaloids in these products may be too low to influence food intake.
Topics: Alkaloids; Animals; Appetite Depressants; Conditioning, Operant; Dose-Response Relationship, Drug; Electronic Nicotine Delivery Systems; Feeding Behavior; Food Deprivation; Male; Nicotine; Rats; Rats, Sprague-Dawley; Nicotiana; Tobacco Products; Tobacco, Smokeless
PubMed: 29196096
DOI: 10.1016/j.pbb.2017.11.004 -
PloS One 2017Floral phytochemicals are ubiquitous in nature, and can function both as antimicrobials and as insecticides. Although many phytochemicals act as toxins and deterrents to...
BACKGROUND
Floral phytochemicals are ubiquitous in nature, and can function both as antimicrobials and as insecticides. Although many phytochemicals act as toxins and deterrents to consumers, the same chemicals may counteract disease and be preferred by infected individuals. The roles of nectar and pollen phytochemicals in pollinator ecology and conservation are complex, with evidence for both toxicity and medicinal effects against parasites. However, it remains unclear how consistent the effects of phytochemicals are across different parasite lineages and environmental conditions, and whether pollinators actively self-medicate with these compounds when infected.
APPROACH
Here, we test effects of the nectar alkaloid anabasine, found in Nicotiana, on infection intensity, dietary preference, and survival and performance of bumble bees (Bombus impatiens). We examined variation in the effects of anabasine on infection with different lineages of the intestinal parasite Crithidia under pollen-fed and pollen-starved conditions.
RESULTS
We found that anabasine did not reduce infection intensity in individual bees infected with any of four Crithidia lineages that were tested in parallel, nor did anabasine reduce infection intensity in microcolonies of queenless workers. In addition, neither anabasine nor its isomer, nicotine, was preferred by infected bees in choice experiments, and infected bees consumed less anabasine than did uninfected bees under no-choice conditions. Furthermore, anabasine exacerbated the negative effects of infection on bee survival and microcolony performance. Anabasine reduced infection in only one experiment, in which bees were deprived of pollen and post-pupal contact with nestmates. In this experiment, anabasine had antiparasitic effects in bees from only two of four colonies, and infected bees exhibited reduced-rather than increased-phytochemical consumption relative to uninfected bees.
CONCLUSIONS
Variation in the effect of anabasine on infection suggests potential modulation of tritrophic interactions by both host genotype and environmental variables. Overall, our results demonstrate that Bombus impatiens prefer diets without nicotine and anabasine, and suggest that the medicinal effects and toxicity of anabasine may be context dependent. Future research should identify the specific environmental and genotypic factors that determine whether nectar phytochemicals have medicinal or deleterious effects on pollinators.
Topics: Anabasine; Animals; Bees; Host-Parasite Interactions; Infections
PubMed: 28832668
DOI: 10.1371/journal.pone.0183729 -
PloS One 2017Oilseed rape (Brassica napus) is an important combinable break crop in the UK, which is largely protected from arthropod pests by insecticidal chemicals. Despite ongoing... (Comparative Study)
Comparative Study
Oilseed rape (Brassica napus) is an important combinable break crop in the UK, which is largely protected from arthropod pests by insecticidal chemicals. Despite ongoing debate regarding the use of neonicotinoids, the dominant seed treatment ingredients used for this crop, there is little publicly available data comparing the efficacy of insecticides in controlling key arthropod pests or comparing the impacts on non-target species and the wider environment. To provide an insight into these matters, a UK-wide expert survey targeting agronomists and entomologists was conducted from March to June 2015. Based on the opinions of 90 respondents, an average of 20% yield loss caused by the key arthropod pests was expected to have occurred in the absence of insecticide treatments. Relatively older chemical groups were perceived to have lower efficacy for target pests than newer ones, partly due to the development of insecticide resistance. Without neonicotinoid seed treatments, a lack of good control for cabbage stem flea beetle was perceived. Wide spectrum foliar insecticide sprays were perceived to have significantly greater negative impacts than seed treatments on users' health, natural enemies, pollinators, soil and water, and many foliar active ingredients have had potential risks for non-target arthropod species in UK oilseed rape fields for the past 25 years. Overall, 72% of respondents opposed the neonicotinoid restriction, while 10% supported it. Opposition and support of the restriction were largely based on concerns for pollinators and the wider environment, highlighting the uncertainty over the side effects of neonicotinoid use. More people from the government and research institutes leaned towards neutrality over the issue, compared to those directly involved in growing the crop. Neonicotinoid restriction was expected to result in greater effort and expenditure on pest control and lower production (0-1 t/ha less). Alternatives for future oilseed rape protection were then discussed.
Topics: Anabasine; Animals; Arthropods; Brassica napus; Crops, Agricultural; Humans; Insect Control; Insecticide Resistance; Insecticides; Pollination; Soil; United Kingdom; Water
PubMed: 28076392
DOI: 10.1371/journal.pone.0169475 -
Genetics Jan 2017Nicotinic acetylcholine receptors (nAChRs) are a highly conserved gene family that form pentameric receptors involved in fast excitatory synaptic neurotransmission. The...
Nicotinic acetylcholine receptors (nAChRs) are a highly conserved gene family that form pentameric receptors involved in fast excitatory synaptic neurotransmission. The specific roles individual nAChR subunits perform in Drosophila melanogaster and other insects are relatively uncharacterized. Of the 10 D. melanogaster nAChR subunits, only three have described roles in behavioral pathways; Dα3 and Dα4 in sleep, and Dα7 in the escape response. Other subunits have been associated with resistance to several classes of insecticides. In particular, our previous work has demonstrated that an allele of the Dα1 subunit is associated with resistance to neonicotinoid insecticides. We used ends-out gene targeting to create a knockout of the Dα1 gene to facilitate phenotypic analysis in a controlled genetic background. To our knowledge, this is the first report of a native function for any nAChR subunits known to be targeted by insecticides. Loss of Dα1 function was associated with changes in courtship, sleep, longevity, and insecticide resistance. While acetylcholine signaling had previously been linked with mating behavior and reproduction in D. melanogaster, no specific nAChR subunit had been directly implicated. The role of Dα1 in a number of behavioral phenotypes highlights the importance of understanding the biological roles of nAChRs and points to the fitness cost that may be associated with neonicotinoid resistance.
Topics: Acetylcholine; Anabasine; Animals; Drosophila Proteins; Drosophila melanogaster; Female; Gene Expression; Insecticide Resistance; Insecticides; Male; Receptors, Nicotinic
PubMed: 28049707
DOI: 10.1534/genetics.116.195750 -
International Journal For Parasitology.... Apr 2017Nematode parasites infect ∼2 billion people world-wide. Infections are treated and prevented by anthelmintic drugs, some of which act on nicotinic acetylcholine...
Nematode parasites infect ∼2 billion people world-wide. Infections are treated and prevented by anthelmintic drugs, some of which act on nicotinic acetylcholine receptors (nAChRs). There is an unmet need for novel therapeutic agents because of concerns about the development of resistance. We have selected Asu-ACR-16 from a significant nematode parasite genus, Ascaris suum, as a pharmaceutical target and nicotine as our basic moiety (EC 6.21 ± 0.56 μM, I 82.39 ± 2.52%) to facilitate the development of more effective anthelmintics. We expressed Asu-ACR-16 in Xenopus oocytes and used two-electrode voltage clamp electrophysiology to determine agonist concentration-current-response relationships and determine the potencies (ECs) of the agonists. Here, we describe the synthesis of a novel agonist, (S)-5-ethynyl-anabasine, and show that it is more potent (EC 0.14 ± 0.01 μM) than other nicotine alkaloids on Asu-ACR-16. Agonists acting on ACR-16 receptors have the potential to circumvent drug resistance to anthelmintics, like levamisole, that do not act on the ACR-16 receptors.
Topics: Anabasine; Animals; Ascaris suum; Drug Discovery; Levamisole; Nicotinic Agonists; Oocytes; Receptors, Nicotinic; Xenopus
PubMed: 28033523
DOI: 10.1016/j.ijpddr.2016.12.001 -
Scientific Reports Nov 2016Nectar and pollen contain diverse phytochemicals that can reduce disease in pollinators. However, prior studies showed variable effects of nectar chemicals on infection,...
Nectar and pollen contain diverse phytochemicals that can reduce disease in pollinators. However, prior studies showed variable effects of nectar chemicals on infection, which could reflect variable phytochemical resistance among parasite strains. Inter-strain variation in resistance could influence evolutionary interactions between plants, pollinators, and pollinator disease, but testing direct effects of phytochemicals on parasites requires elimination of variation between bees. Using cell cultures of the bumble bee parasite Crithidia bombi, we determined (1) growth-inhibiting effects of nine floral phytochemicals and (2) variation in phytochemical resistance among four parasite strains. C. bombi growth was unaffected by naturally occurring concentrations of the known antitrypanosomal phenolics gallic acid, caffeic acid, and chlorogenic acid. However, C. bombi growth was inhibited by anabasine, eugenol, and thymol. Strains varied >3-fold in phytochemical resistance, suggesting that selection for phytochemical resistance could drive parasite evolution. Inhibitory concentrations of thymol (4.53-22.2 ppm) were similar to concentrations in Thymus vulgaris nectar (mean 5.2 ppm). Exposure of C. bombi to naturally occurring levels of phytochemicals-either within bees or during parasite transmission via flowers-could influence infection in nature. Flowers that produce antiparasitic phytochemicals, including thymol, could potentially reduce infection in Bombus populations, thereby counteracting a possible contributor to pollinator decline.
Topics: Anabasine; Animals; Bees; Cells, Cultured; Crithidia; Eugenol; Host-Parasite Interactions; Phytochemicals; Thymol; Thymus Plant
PubMed: 27883009
DOI: 10.1038/srep37087