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1.
BMC Public Health ; 21(1): 1786, 2021 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-34600513

RESUMO

BACKGROUND: Much of what is known about COVID-19 risk factors comes from patients with serious symptoms who test positive. While risk factors for hospitalization or death include chronic conditions and smoking; less is known about how health status or nicotine consumption is associated with risk of SARS-CoV-2 infection among individuals who do not present clinically. METHODS: Two community-based population samples (including individuals randomly and nonrandomly selected for statewide testing, n = 8214) underwent SARS-CoV-2 testing in nonclinical settings. Each participant was tested for current (viral PCR) and past (antibody) infection in either April or June of 2020. Before testing, participants provided demographic information and self-reported health status and nicotine and tobacco behaviors (smoking, chewing, vaping/e-cigarettes). Using descriptive statistics and a bivariate logistic regression model, we examined the association between health status and use of tobacco or nicotine with SARS-CoV-2 positivity on either PCR or antibody tests. RESULTS: Compared to people with self-identified "excellent" or very good health status, those reporting "good" or "fair" health status had a higher risk of past or current infections. Positive smoking status was inversely associated with SARS-CoV-2 infection. Chewing tobacco was associated with infection and the use of vaping/e-cigarettes was not associated with infection. CONCLUSIONS: In a statewide, community-based population drawn for SARS-CoV-2 testing, we find that overall health status was associated with infection rates. Unlike in studies of COVID-19 patients, smoking status was inversely associated with SARS-CoV-2 positivity. More research is needed to further understand the nature of this relationship.


Assuntos
COVID-19 , Sistemas Eletrônicos de Liberação de Nicotina , Teste para COVID-19 , Nível de Saúde , Humanos , Nicotina/efeitos adversos , SARS-CoV-2
2.
BMJ Open ; 11(9): e045724, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493505

RESUMO

OBJECTIVES: To provide a consensus from a panel of international experts about electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP). DESIGN: Cross-sectional survey. METHODS: A Delphi survey was conducted among international experts in tobacco control and smoking cessation. The first part addressed statements or recommendations about ENDS, the second about HTP, both divided into four categories: regulation, sale, use and general issues. SETTING: Experts from 15 countries. PARTICIPANTS: Individuals with clinical, public health or research expertise in tobacco control and/or smoking cessation. RESULTS: 268 experts were contacted, 92 (34%) completed the first, 55/92 (60%) the second round. Consensus for ENDS: components of e-liquids, an upper limit of nicotine concentration should be defined; a warning on the lack of evidence in long-term safety and addiction potential should be stated; ENDS should not be regulated as consumer products but either as a new category of nicotine delivery or tobacco products; ENDS should not be sold in general stores but in specialised shops, shops selling tobacco or in pharmacies with restriction on sale to minors; administration of illegal drugs is likely with ENDS. Consensus for HTP: HTP have the same addictive potential as cigarettes; they should be regulated as a tobacco product with similar warning messages as cigarettes; their advertisement should not be allowed. ENDS and HTP use should not be allowed in indoor public places; a specific tax should be implemented for ENDS, taxes on HTP should not be lower than those for cigarettes; use of cigarettes is more likely with both ENDS and HTP (dual use) than quitting smoking. CONCLUSIONS: Experts in tobacco control and/or smoking cessation recommend differential regulation for ENDS and HTP. The results of this survey may be useful for health authorities, decision makers and researchers of the tobacco use and cessation field.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Consenso , Estudos Transversais , Humanos , Nicotina
3.
Int J Mol Sci ; 22(16)2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34445737

RESUMO

Cholinergic neurotransmission is a key signal pathway in the peripheral nervous system and in several branches of the central nervous system. Despite the fact that it has been studied extensively for a long period of time, some aspects of its regulation still have not yet been established. One is the relationship between the nicotine-induced autoregulation of acetylcholine (ACh) release with changes in the concentration of presynaptic calcium levels. The mouse neuromuscular junction of m. Levator Auris Longus was chosen as the model of the cholinergic synapse. ACh release was assessed by electrophysiological methods. Changes in calcium transients were recorded using a calcium-sensitive dye. Nicotine hydrogen tartrate salt application (10 µM) decreased the amount of evoked ACh release, while the calcium transient increased in the motor nerve terminal. Both of these effects of nicotine were abolished by the neuronal ACh receptor antagonist dihydro-beta-erythroidine and Cav1 blockers, verapamil, and nitrendipine. These data allow us to suggest that neuronal nicotinic ACh receptor activation decreases the number of ACh quanta released by boosting calcium influx through Cav1 channels.


Assuntos
Acetilcolina/metabolismo , Canais de Cálcio Tipo L/metabolismo , Cálcio/metabolismo , Neurônios Motores/metabolismo , Junção Neuromuscular/metabolismo , Animais , Eletrodiagnóstico , Feminino , Técnicas In Vitro , Masculino , Camundongos Endogâmicos BALB C , Nicotina , Canais de Potássio Cálcio-Ativados/metabolismo
4.
Transl Psychiatry ; 11(1): 441, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429396

RESUMO

The majority of smokers relapse even after successfully quitting because of the craving to smoking after unexpectedly re-exposed to smoking-related cues. This conditioned craving is mediated by reward memories that are frequently experienced and stubbornly resistant to treatment. Reconsolidation theory posits that well-consolidated memories are destabilized after retrieval, and this process renders memories labile and vulnerable to amnestic intervention. This study tests the retrieval reconsolidation procedure to decrease nicotine craving among people who smoke. In this study, 52 male smokers received a single dose of propranolol (n = 27) or placebo (n = 25) before the reactivation of nicotine-associated memories to impair the reconsolidation process. Craving for smoking and neural activity in response to smoking-related cues served as primary outcomes. Functional magnetic resonance imaging was performed during the memory reconsolidation process. The disruption of reconsolidation by propranolol decreased craving for smoking. Reactivity of the postcentral gyrus in response to smoking-related cues also decreased in the propranolol group after the reconsolidation manipulation. Functional connectivity between the hippocampus and striatum was higher during memory reconsolidation in the propranolol group. Furthermore, the increase in coupling between the hippocampus and striatum positively correlated with the decrease in craving after the reconsolidation manipulation in the propranolol group. Propranolol administration before memory reactivation disrupted the reconsolidation of smoking-related memories in smokers by mediating brain regions that are involved in memory and reward processing. These findings demonstrate the noradrenergic regulation of memory reconsolidation in humans and suggest that adjunct propranolol administration can facilitate the treatment of nicotine dependence. The present study was pre-registered at ClinicalTrials.gov (registration no. ChiCTR1900024412).


Assuntos
Propranolol , Tabagismo , Sinais (Psicologia) , Humanos , Masculino , Memória , Nicotina , Fumantes , Tabagismo/tratamento farmacológico
5.
Molecules ; 26(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34443380

RESUMO

The popular tobacco and e-cigarette chemical flavorant (-)-menthol acts as a nonselective, noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs), and contributes to multiple physiological effects that exacerbates nicotine addiction-related behavior. Menthol is classically known as a TRPM8 agonist; therefore, some have postulated that TRPM8 antagonists may be potential candidates for novel nicotine cessation pharmacotherapies. Here, we examine a novel class of TRPM8 antagonists for their ability to alter nicotine reward-related behavior in a mouse model of conditioned place preference. We found that these novel ligands enhanced nicotine reward-related behavior in a mouse model of conditioned place preference. To gain an understanding of the potential mechanism, we examined these ligands on mouse α4ß2 nAChRs transiently transfected into neuroblastoma-2a cells. Using calcium flux assays, we determined that these ligands act as positive modulators (PMs) on α4ß2 nAChRs. Due to α4ß2 nAChRs' important role in nicotine dependence, as well as various neurological disorders including Parkinson's disease, the identification of these ligands as α4ß2 nAChR PMs is an important finding, and they may serve as novel molecular tools for future nAChR-related investigations.


Assuntos
Comportamento Animal/efeitos dos fármacos , Nicotina/farmacologia , Receptores Nicotínicos/metabolismo , Recompensa , Animais , Cálcio/metabolismo , Feminino , Masculino , Camundongos Endogâmicos C57BL , Fatores de Tempo
7.
Accid Anal Prev ; 160: 106341, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34392006

RESUMO

OBJECTIVE: While alcohol, marijuana, and nicotine are the most commonly used substances, there is limited research on the between- and within-person associations of their use and driving under the influence (DUI) and riding with an impaired driver (RWID). The current study utilized a burst design to assess how use and co-use of these substances is associated with DUI and RWID. METHODS: College student drinkers with past-year marijuana and/or nicotine use (N = 367) were assessed on two consecutive weekends for three semesters. Logistic regression compared students who only reported drinking to student drinkers who used marijuana, nicotine, or all three substances on likelihood to DUI and RWID. Multilevel logistic models assessed the associations of varied combinations of substances with the daily likelihood of DUI and RWID. RESULTS: Compared to students who only used alcohol, students who also reported marijuana use were more likely to DUI (OR = 5.44), and students who reported use of alcohol, nicotine and marijuana more likely to DUI (OR = 10.33) and RWID (OR = 10.22). Compared to occasions when only alcohol was used, DUI was more likely on marijuana only occasions (OR = 9.08), and RWID was more likely on alcohol and marijuana occasions (OR = 3.86). However, confidence intervals were wide for effects. DISCUSSION: Students reporting use of all 3 substances had higher overall risk of DUI and RWID indicating prevention efforts for DUI and RWID should include all substances. Implications for prevention and intervention strategies at the individual and environmental level are discussed.


Assuntos
Condução de Veículo , Cannabis , Dirigir sob a Influência , Acidentes de Trânsito , Consumo de Bebidas Alcoólicas/epidemiologia , Humanos , Nicotina , Estudantes
8.
Artigo em Inglês | MEDLINE | ID: mdl-34360221

RESUMO

Nicotine vaping products (NVPs) have evolved rapidly, and some vapers have difficulty reporting about their NVP. NVP knowledge may be important for providing accurate survey data, understanding the potential risks of NVP use, and assessing legal and regulated products. This paper examines current vapers who responded "don't know" (DK) regarding their NVP features. Data are from adult daily/weekly vapers in Waves Two (2018, n = 4192) and Three (2020, n = 3894) of the ITC Four Country Smoking and Vaping Survey. Analyses assessed DK responses for NVP features (e.g., type/appearance, nicotine) and consumption. A DK index score was computed based on the percent of all features with DK responses, which was tested for associations with demographics, smoking/vaping status, NVP features, purchase location, and knowledge of NVP relative risks. NVP description and appearance were easily identified, but DK was more common for features such as nicotine content (7.3-9.2%) and tank/cartridge volume capacity (26.6-30.0%). DK responses often differed by vaping/smoking status, NVP type/appearance, purchase location, and country. Vapers who are younger, use box-shaped NVPs, purchase online, and exclusive daily vapers were associated with lower DK index scores. Higher DK index scores were associated with poorer knowledge of relative health risks of NVP use. The diversity of the NVP market and wide variation in how products are used makes it challenging to capture information from users about device features, such as nicotine content and capacity, in population surveys.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Vaping , Adulto , Humanos , Nicotina , Fumantes , Fumar
9.
Science ; 373(6556)2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34385370

RESUMO

The neurotransmitter acetylcholine (ACh) acts in part through a family of nicotinic ACh receptors (nAChRs), which mediate diverse physiological processes including muscle contraction, neurotransmission, and sensory transduction. Pharmacologically, nAChRs are responsible for tobacco addiction and are targeted by medicines for hypertension and dementia. Nicotinic AChRs were the first ion channels to be isolated. Recent studies have identified molecules that control nAChR biogenesis, trafficking, and function. These nAChR accessories include protein and chemical chaperones as well as auxiliary subunits. Whereas some factors act on many nAChRs, others are receptor specific. Discovery of these regulatory mechanisms is transforming nAChR research in cells and tissues ranging from central neurons to spinal ganglia to cochlear hair cells. Nicotinic AChR-specific accessories also enable drug discovery on high-confidence targets for psychiatric, neurological, and auditory disorders.


Assuntos
Chaperonas Moleculares/metabolismo , Neurônios/metabolismo , Proteínas/metabolismo , Receptores Nicotínicos/metabolismo , Animais , Membrana Celular/metabolismo , Descoberta de Drogas , Retículo Endoplasmático/metabolismo , Humanos , Ligantes , Músculo Esquelético/metabolismo , Neurofarmacologia , Nicotina/metabolismo , Subunidades Proteicas/metabolismo , Receptores Nicotínicos/química
10.
Neuron ; 109(16): 2505-2507, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34411537

RESUMO

In this issue of Neuron, Nguyen and colleagues (Nguyen et al., 2021) investigate nicotine's effects on diverse midbrain dopamine neurons. Their findings provide new understanding of the functional role of ventral tegmental area (VTA) dopamine neurons and reveal topographically distinct, pathway-specific, and opposite dopaminergic responses to nicotine that likely mediate reward and anxiety, respectively.


Assuntos
Dopamina , Nicotina , Ansiedade , Neurônios Dopaminérgicos , Nicotina/farmacologia , Recompensa , Área Tegmentar Ventral
11.
Medicina (Kaunas) ; 57(8)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34440946

RESUMO

Recent studies have explored improvements in smoking prevention and cessation to reduce smoking prevalence, however, in Europe, only Finland has already set a date to become nicotine free. Studies reporting on central, eastern and southern Europe have mostly focused on combustible cigarettes up to now. In young people, correlations were found between traditional smoking, the "vaping" of e-cigarettes, experimentation with alcohol intoxication, and the use of illicit drugs. Prevention and cessation should include strategies against active and passive exposures to new nicotine products. This is a prerequisite for a successful public health policy and a future end-game against the business interests of the tobacco industry and its allies.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Produtos do Tabaco , Adolescente , Humanos , Nicotina , Tabaco
12.
Artigo em Inglês | MEDLINE | ID: mdl-34444601

RESUMO

Background: To gauge the public health impact of new nicotine products, information is needed on use among different populations. Aims were to assess in adults who smoked, vaped, did both or had recently stopped: (1) awareness, ever and current use of heated tobacco products (HTPs) and nicotine pouches (NP), (2) characteristics associated with ever use, (3) reasons for use of and satisfaction with HTPs, (4) characteristics associated with interest in use of HTPs. Methods: Online survey in the UK in 2019, n = 3883. (1) Proportion aware, ever and current (≥monthly) use; (2) ever use regressed onto socio-demographics and smoking/vaping; (3) frequency of reasons for HTP use and satisfaction; (4) interest in trying HTPs regressed onto socio-demographics and smoking/vaping status. Results: Awareness was 34.8% for HTP and 15.9% for NP; current use was 3.2% and 2.7%. Being <45 years, higher education, living in London and currently both smoking and vaping were associated with ever having used the products. Curiosity was the most common reason for HTP use (79.8%) and 72.0% of ever HTP users found them at least as satisfying as smoking. Among those not currently using HTPs, 48.5% expressed any interest-lower among those aged over 65 and higher among those smoking and vaping. Conclusions: In this sample of adults with a history of nicotine use, very few currently used heated tobacco products or nicotine pouches. Satisfaction with and interest in HTPs were substantial. The low level of use is unlikely to substantially reduce the public health impact of smoking.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Adulto , Idoso , Humanos , Nicotina , Fumar , Reino Unido/epidemiologia
13.
Drug Alcohol Depend ; 226: 108870, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34216863

RESUMO

BACKGROUND: Establishing preclinical models of the development of nicotine withdrawal following acute nicotine exposure could inform tobacco addiction-related research, treatment, and policy. To this end, this lab has previously reported that rats exhibit withdrawal-like elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) following acute nicotine exposure. The goal of this study was to provide further pharmacological characterization of ICSS as a measure of spontaneous and antagonist-precipitated withdrawal from acute nicotine. METHODS AND RESULTS: Rats exhibited a small increase in ICSS thresholds over time following a single nicotine injection (1.0 mg/kg, s.c.), suggesting a modest spontaneous withdrawal effect (Experiment 1). In Experiment 2, the antidepressant bupropion (5.0 mg/kg, i.p.), which is used to treat tobacco addiction and attenuates nicotine withdrawal in both humans and rodents, blocked elevations in ICSS thresholds induced by a single injection of nicotine (0.5 mg/kg, s.c.) followed ≈ 2 h later by the non-selective, non-competitive nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (3.0 mg/kg, s.c.). In Experiment 3a, s.c. administration of the competitive, relatively selective α4ß2 nAChR antagonist dihydro-beta-erythroidine (DHßE) (5.6 mg/kg, but not 3.0 mg/kg) following each of 5 daily injections of nicotine (0.5 mg/kg, s.c.) elevated ICSS thresholds. Mecamylamine (3.0 mg/kg, s.c.) also elevated ICSS thresholds when administered following all 5 daily nicotine injections (0.5 mg/kg, s.c., Experiment 3b). CONCLUSIONS: These findings provide further characterization of elevations in ICSS thresholds as a measure of withdrawal from acute nicotine exposure. Further use of these models may be useful for understanding the early development of nicotine withdrawal.


Assuntos
Nicotina , Síndrome de Abstinência a Substâncias , Animais , Mecamilamina/farmacologia , Antagonistas Nicotínicos/farmacologia , Ratos , Autoestimulação , Síndrome de Abstinência a Substâncias/tratamento farmacológico
14.
Molecules ; 26(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34299660

RESUMO

Arthrobacter nicotinovorans decomposes nicotine through the pyridine pathway. 6-hydroxypseudooxynicotine 2-oxidoreductase (also named ketone dehydrogenase, Kdh) is an important enzyme in nicotine degradation pathway of A. nicotinovorans, and is responsible for the second hydroxylation of nicotine. Kdh belongs to the molybdenum hydroxylase family, and catalyzes the oxidation of 6-hydroxy-pseudooxynicotine (6-HPON) to 2,6-dihydroxy-pseudooxynicotine (2,6-DHPON). We determined the crystal structure of the Kdh holoenzyme from A. nicotinovorans, with its three subunits KdhL, KdhM, and KdhS, and their associated cofactors molybdopterin cytosine dinucleotide (MCD), two iron-sulfur clusters (Fe2S2), and flavin adenine dinucleotide (FAD), respectively. In addition, we obtained a structural model of the substrate 6-HPON-bound Kdh through molecular docking, and performed molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations to unveil the catalytic mechanism of Kdh. The residues Glu345, Try551, and Glu748 of KdhL were found to participate in substrate binding, and Phe269 and Arg383 of KdhL were found to contribute to stabilize the MCD conformation. Furthermore, site-directed mutagenesis and enzymatic activity assays were performed to support our structural and computational results, which also revealed a trend of increasing catalytic efficiency with the increase in the buffer pH. Lastly, our electrochemical results demonstrated electron transfer among the various cofactors of Kdh. Therefore, our work provides a comprehensive structural, mechanistic, and functional study on the molybdenum hydroxylase Kdh in the nicotine degradation pathway of A. nicotinovorans.


Assuntos
Proteínas de Bactérias/química , Micrococcaceae/enzimologia , Oxigenases de Função Mista/química , Simulação de Acoplamento Molecular , Molibdênio/química , Nicotina/química , Proteínas de Bactérias/genética , Clonagem Molecular , Nucleotídeos de Citosina/química , Nucleotídeos de Citosina/genética , Micrococcaceae/genética , Oxigenases de Função Mista/genética , Molibdênio/metabolismo , Nicotina/metabolismo , Pterinas/química , Relação Estrutura-Atividade
15.
Exp Clin Psychopharmacol ; 29(3): 279-287, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34264738

RESUMO

The U.S. Food and Drug Administration has the authority to regulate characteristics of electronic nicotine delivery systems (ENDS). Prior research indicates that regulation of certain characteristics of these products may have an effect on their appeal and use. Policies that affect appeal and use of ENDS are relevant to attempts to reduce use among young people-including young adults-but are also relevant to adults who use these products as harm reduction tools. Using a novel concurrent choice task, we evaluated the relative reinforcement of JUUL brand ENDS products that varied in flavor (n = 8) and nicotine (n = 8) among samples of young adults who use JUUL. Findings suggest that restricting JUUL flavor to tobacco-only results in decreased appeal, while reducing the nicotine content of JUUL pods to 3%-from the conventional 5%-does not have an effect on product appeal. Findings also validate a novel methodology for delivering fixed doses of ENDS vapor within the context of a task that assesses the relative reinforcement of ENDS products with varying characteristics. This methodology can be applied to assessing the relative reinforcing effects of a wide variety of tobacco products with varied characteristics. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Comportamento do Consumidor/estatística & dados numéricos , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Aromatizantes/administração & dosagem , Nicotina/administração & dosagem , Reforço Psicológico , Adolescente , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
16.
Addict Behav ; 122: 107051, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34303118

RESUMO

INTRODUCTION: When considering the clinical efficacy of e-cigarettes for smoking cessation, non-pharmacologic influences, such as conditioned reinforcers (e.g. sensorimotor stimuli), must be considered in addition to nicotine. The present study parsed the influences of nicotine delivery and sensorimotor stimuli (i.e, similarity to smoking) on cravings and other immediate outcomes of e-cigarette use. METHOD: Participants (N = 127 dual users) completed an experimental ad-lib vaping session in one of 4 conditions: Drug (open label nicotine vs non-nicotine e-cigarettes) crossed with delivery apparatus (normal e-cigarette vs altered sensorimotor apparatus). It was hypothesized that participants who were deprived of the usual vaping stimuli would report less craving reduction via vaping. Nicotine was hypothesized to enhance physiological outcomes. RESULTS: Moderate effects emerged for nicotine, whereas smaller effects were observed for the sensorimotor manipulation upon both cravings to smoke and cravings to vape. Contrary to the hypothesis, participants who vaped using the altered sensorimotor apparatus reported greater craving reduction compared to those who used normal e-cigarettes. Nicotine delivery also had moderate effects on psychological reward. Main effects were not moderated by gender, withdrawal, or dependence. CONCLUSIONS: Findings support the role of nicotine in reducing cravings via vaping. They also suggest that sensorimotor similarities to smoking may be less important among experienced vapers or dual users. Indeed, in this sample, the altered sensorimotor apparatus may have reduced craving via distraction or other mechanisms.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotina , Vaping , Fissura , Humanos , Nicotina/efeitos adversos
17.
Plant Mol Biol ; 107(1-2): 21-36, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34302568

RESUMO

KEY MESSAGE: NtARF6 overexpression represses nicotine biosynthesis in tobacco. Transcriptome analysis suggests that NtARF6 acts as a regulatory hub that connect different phytohormone signaling pathways to antagonize the jasmonic acid-induced nicotine biosynthesis. Plant specialized metabolic pathways are regulated by a plethora of molecular regulators that form complex networks. In Nicotiana tabacum, nicotine biosynthesis is regulated by transcriptional activators, such as NtMYC2 and the NIC2-locus ERFs. However, the underlying molecular mechanism of the regulatory feedback is largely unknown. Previous research has shown that NbARF1, a nicotine synthesis repressor, reduces nicotine accumulation in N. benthamiana. In this study, we demonstrated that overexpression of NtARF6, an ortholog of NbARF1, was able to reduce pyridine alkaloid accumulation in tobacco. We found that NtARF6 could not directly repress the transcriptional activities of the key nicotine pathway structural gene promoters. Transcriptomic analysis suggested that this NtARF6-induced deactivation of alkaloid biosynthesis might be achieved by the antagonistic effect between jasmonic acid (JA) and other plant hormone signaling pathways, such as ethylene (ETH), salicylic acid (SA), abscisic acid (ABA). The repression of JA biosynthesis is accompanied by the induction of ETH, ABA, and SA signaling and pathogenic infection defensive responses, resulting in counteracting JA-induced metabolic reprogramming and decreasing the expression of nicotine biosynthetic genes in vivo. This study provides transcriptomic evidence for the regulatory mechanism of the NtARF6-mediated repression of alkaloid biosynthesis and indicates that this ARF transcription factor might act as a regulatory hub to connect different hormone signaling pathways in tobacco.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Nicotina/biossíntese , Proteínas de Plantas/genética , Tabaco/genética , Alcaloides/metabolismo , Sequência de Aminoácidos , Vias Biossintéticas/genética , Análise por Conglomerados , Ontologia Genética , Genes Reguladores , Genoma de Planta , Especificidade de Órgãos/genética , Filogenia , Células Vegetais/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Ligação Proteica , Saccharomyces cerevisiae/metabolismo , Frações Subcelulares/metabolismo , Transcriptoma/genética
18.
Rev Mal Respir ; 38(7): 706-720, 2021 Sep.
Artigo em Francês | MEDLINE | ID: mdl-34215484

RESUMO

INTRODUCTION: The effectiveness of the three validated smoking cessation medications, nicotine replacement therapy, varenicline and bupropion, may be insufficient, in hard-core smokers. OBJECTIVES: This systematic review investigates the efficacy of combinations of different medications in smoking abstinence and their tolerability. RESULTS: Three randomized controlled trials (RCTs) compared the combined medications with varenicline and nicotine patches vs. varenicline; two found an increase in abstinence rates with the combined medications. In one study, the beneficial effect was only observed in heavy smokers. The four RCTs comparing the combined medications with varenicline and bupropion (vs. varenicline) demonstrated an increase in abstinence rates with the combined medications, most often in heavy smokers who are very dependent on tobacco. The results of the three RCTs comparing the combined medications with bupropion and nicotine replacement therapy vs. varenicline were discordant. Three studies included other molecules (mecamylamine, selegiline, sertraline, buspirone). Combined medications were well tolerated. CONCLUSION: Combination treatments can achieve higher smoking abstinence rates than monotherapies, especially in smokers who have failed to quit (Hard-core smokers). Treatment with a combination of varenicline and nicotine replacement therapy is a therapeutic option in smoking cessation.


Assuntos
Abandono do Hábito de Fumar , Bupropiona/uso terapêutico , Humanos , Nicotina , Fumar , Vareniclina/uso terapêutico
19.
eNeuro ; 8(4)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193508

RESUMO

Developmental nicotine exposure (DNE), alters brainstem neurons that control breathing, including hypoglossal motor neurons (XIIMNs), which innervate the tongue. Here, we tested the hypothesis that chronic, episodic DNE (eDNE), which mimics nicotine replacement therapies such as e-cigarettes or nicotine gum, alters the function of nicotinic acetylcholine receptors (nAChRs), XIIMN intrinsic properties, and tongue muscle function in vivo similar to what we have observed with a chronic, sustained exposure model. We delivered nicotine to pregnant Sprague Dawley rats through drinking water and studied pups of either sex in two age groups: postnatal day (P)1-P5 and P10-P12, which encompasses a critical period in brain development. At P1-P5, eDNE was associated with delayed recovery of nAChRs from desensitization; however, there were no changes in the magnitude of desensitization, XIIMN intrinsic properties, or tongue muscle function in vivo. By P10-P12, eDNE XIIMNs had lower peak firing frequencies in response to depolarizing current injection, larger delayed rectifier potassium currents, and continued to exhibit delayed nAChR recovery. Moreover, this age group exhibited a blunted and delayed tongue muscle response to nasal occlusion in vivo, indicating that changes to XIIMN intrinsic properties is an important mechanism behind this effect, as it is not produced by altered nAChR function alone. Together, these results show that eDNE alters XIIMNs and tongue muscle function during a critical period in brain development and that the specific effects of chronic nicotine exposure may be pattern dependent.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Efeitos Tardios da Exposição Pré-Natal , Receptores Nicotínicos , Abandono do Hábito de Fumar , Animais , Animais Recém-Nascidos , Feminino , Nervo Hipoglosso , Neurônios Motores , Nicotina , Gravidez , Ratos , Ratos Sprague-Dawley , Dispositivos para o Abandono do Uso de Tabaco
20.
Molecules ; 26(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299637

RESUMO

This study intends to valorize by-products of the industrial processing of tobacco to obtain nicotine and phenolics as value-added compounds. Three influential parameters of the microwave-assisted extraction-MAE (temperature, treatment time, and solvent/solid ratio) were studied for the optimization of the extraction protocol for tobacco leaves and three types of waste-scrap, dust, and midrib, respectively. Nicotine was the dominant bioactive compound in all extracts, ranging from 1.512 to 5.480% in leaves, 1.886 to 3.709% in scrap, 2.628 to 4.840% dust, and 0.867 to 1.783% in midrib extracts. Five phenolic compounds were identified and quantified, predominated by chlorogenic acid and rutin. Additionally, total phenol content and antioxidant activity were determined using spectrophotometric assays. Optimization was performed in two aspects: to obtain a maximum extraction yield with minimum nicotine content and to obtain a maximum extraction yield with maximum nicotine content. These findings demonstrate that tobacco waste is a valuable source of bioactive compounds and MAE can be a promising alternative technique to obtain extracts rich in targeted bioactive compounds, especially nicotine.


Assuntos
Antioxidantes , Nicotina , Fenóis , Extratos Vegetais/química , Folhas de Planta/química , Tabaco/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Temperatura Alta , Micro-Ondas , Nicotina/química , Nicotina/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Resíduos Sólidos
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