RESUMO
Objectives: The effects of nicotine metabolism on the kidneys of healthy individuals have not been determined. The nicotine metabolite ratio (NMR) indicates the rate of nicotine metabolism and is linked to smoking behaviors and responses to tobacco treatments. We conducted this study in order to investigated the relationship between nicotine metabolite ratio (NMR) and kidney function. Methods: An analysis of cross-sectional data of adults was conducted using a population survey dataset (National Health and Nutrition Examination Survey Data 2013/2018 of the United States). A weighted multivariate regression analysis was conducted to estimate the correlation between NMR and kidney function. Furthermore, we apply fitting smooth curves to make the relationship between NMR and estimated glomerular filtration rate (eGFR) more visualized. Results: The research included a total of 16153 participants. Weighted multivariate regression analyses adjusted for possible variables showed a negative relationship between NMR and estimated glomerular filtration rate (eGFR).The ß (95%CI) of the regression equation between NMR and eGFR was -2.24 (-2.92, -1.55), the trend testing showed consistent results. NMR is positively correlated with urinary albumin creatinine ratio (uACR), but it is not statistically significant. A stratified analysis found a negative correlation between NMR and eGFR in all age, gender and diabetes subgroups, the results were not statistically significant among Mexican Americans and other races. Notably, each unit rise in NMR corresponded to a 4.54 ml/min·1.73m² lower eGFR in diabetic participants and a 6.04 ml/min·1.73m² lower eGFR in those aged 60 and above. Conclusions: Our study shows that nicotine metabolite ratio is negatively associated with kidney function among most adults. It will be necessary to conduct more well-designed prospective clinical trials in order to determine the exact causal interactions between NMR and kidney function. Specific mechanisms also need to be further explored in basic experiments.
Assuntos
Taxa de Filtração Glomerular , Rim , Nicotina , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Nicotina/metabolismo , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Rim/metabolismo , Idoso , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Introduction. Peri-implantitis is a plaque-associated disease that leads to implant loss and arises from bacterial biofilms on the surface of the implant. Smoking is a risk factor for peri-implantitis and impedes treatment effectiveness. Additionally, aryl hydrocarbon receptor (AHR), IL-6, and IL-22 levels are related to peri-implantitis.Aim. We aimed to investigate the effects of nicotine on inflammatory response, bacterial growth and biofilm formation.Hypothesis/Gap Statement. We hypothesized that nicotine promoted pathogenic bacterial growth and biofilm formation, thereby aggravating inflammation.Methodology. The expression of AHR, IL-6 and IL-22 was measured in peri-implant sulci fluid using quantitative PCR and Western blot analyses. The cementum was incubated with bacterial suspension including Porphyromonas gingivalis, Streptococcus sanguinis and Fusobacterium nucleatum and treated with 100, 200, 250 and 300 µg ml-1 nicotine, and then, the absorbance and number of colony-forming units were detected. Biofilm formation was evaluated using the tissue culture plate method and safranin O staining. Carbohydrates and proteins were measured by the phenol-sulfuric acid method and the bicinchoninic acid method, respectively.Results. The results indicated that smoking increased the levels of AHR, IL-6 and IL-22. Functionally, nicotine promoted the growth of P. gingivalis, S. sanguinis and F. nucleatum. Additionally, it promoted the biofilm formation of these bacteria and increased the contents of carbohydrates and proteins.Conclusion. Nicotine promoted bacterial growth and biofilm build-up, suggesting that smoking may aggravate the progression of peri-implantitis.
Assuntos
Biofilmes , Nicotina , Peri-Implantite , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Nicotina/farmacologia , Humanos , Peri-Implantite/microbiologia , Fusobacterium nucleatum/efeitos dos fármacos , Fusobacterium nucleatum/crescimento & desenvolvimento , Fusobacterium nucleatum/fisiologia , Porphyromonas gingivalis/efeitos dos fármacos , Porphyromonas gingivalis/crescimento & desenvolvimento , Masculino , Implantes Dentários/microbiologia , Feminino , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Interleucinas/metabolismo , Streptococcus sanguis/efeitos dos fármacos , Streptococcus sanguis/crescimento & desenvolvimento , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Fumar/efeitos adversosRESUMO
INTRODUCTION: To assess nicotine-containing products (NCPs; heated tobacco products and/or electronic cigarettes) use in relation to conventional smoking. METHODS: "LOST IN ITALY" ("LOckdown and Lifestyles IN ITALY") and "LOST IN TOSCANA" cross-sectional surveys estimated lifestyles changes before, during, and after the lockdown in a representative sample of the Italian population. A Poisson regression model was used to estimate prevalence ratios of NCP use according to socio-demographic, mental distress, and smoking variables. RESULTS: The prevalence of conventional cigarette smokers did not decrease, remaining stable at 23%. Exclusive conventional cigarette smokers decreased from 21% before the lockdown in 2020 to 15% in 2023 but dual users, representing the large majority of NCP users, increased by 4 times, and exclusive NCP users decreased from 7% in 2020 to 5% in 2023. CONCLUSIONS: NCPs are mostly accompanying instead of replacing conventional cigarettes. A targeted campaign should be developed in Italy to raise awareness on that.
Assuntos
COVID-19 , Humanos , Itália/epidemiologia , COVID-19/epidemiologia , Adulto , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Produtos do Tabaco , Pandemias , Adolescente , Nicotina , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Prevalência , Fumar/epidemiologia , SARS-CoV-2RESUMO
Background: Lung is the largest mucosal area of the human body and directly connected to the external environment, facing microbial exposure and environmental stimuli. Therefore, studying the internal microorganisms of the lung is crucial for a deeper understanding of the relationship between microorganisms and the occurrence and progression of lung cancer. Methods: Tumor and adjacent nontumor tissues were collected from 38 lung adenocarcinoma patients and used nanopore sequencing technology to sequence the 16s full-length sequence of bacteria, and combining bioinformatics methods to identify and quantitatively analyze microorganisms in tissues, as well as to enrich the metabolic pathways of microorganisms. Results: the microbial composition in lung adenocarcinoma tissues is highly similar to that in adjacent tissues, but the alpha diversity is significantly lower than that in adjacent tissues. The difference analysis results show that the bacterial communities of Streptococcaceae, Lactobacillaceae, and Neisseriales were significantly enriched in cancer tissues. The results of metabolic pathway analysis indicate that pathways related to cellular communication, transcription, and protein synthesis were significantly enriched in cancer tissue. In addition, clinical staging analysis of nicotine exposure and lung cancer found that Haemophilus, paralinfluenzae, Streptococcus gordonii were significantly enriched in the nicotine exposure group, while the microbiota of Cardiobactereae and Cardiobacterales were significantly enriched in stage II tumors. The microbiota significantly enriched in IA-II stages were Neisseriaeae, Enterobacteriales, and Cardiobacterales, respectively. Conclusion: Nanopore sequencing technology was performed on the full length 16s sequence, which preliminarily depicted the microbial changes and enrichment of microbial metabolic pathways in tumor and adjacent nontumor tissues. The relationship between nicotine exposure, tumor progression, and microorganisms was explored, providing a theoretical basis for the treatment of lung cancer through microbial targets.
Assuntos
Adenocarcinoma de Pulmão , Bactérias , Neoplasias Pulmonares , Microbiota , Sequenciamento por Nanoporos , Nicotina , Humanos , Adenocarcinoma de Pulmão/microbiologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Microbiota/genética , Nicotina/metabolismo , Masculino , Feminino , Neoplasias Pulmonares/microbiologia , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Sequenciamento por Nanoporos/métodos , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Idoso , RNA Ribossômico 16S/genética , Pulmão/microbiologia , Pulmão/patologia , Biologia Computacional/métodos , Redes e Vias Metabólicas/genéticaRESUMO
The neurohormone oxytocin (OT) has been proposed as a treatment for alcohol and nicotine use disorders. The aim of the present study was to examine whether intravenous (IV) OT decreases alcohol oral self-administration and consumption in nonhuman primates under a 6-h alcohol access procedure as well as alcohol and nicotine (IV) self-administration under 6-h concurrent access conditions. The subjects were five male baboons (Papio anubis) that self-administered oral alcohol (4% w/v) during 6-h sessions under a fixed ratio 3 (FR3) schedule per drink. Baseline levels of alcohol self-administration were established and then OT treatment was initiated. A single dose of OT (20, 40, 80, 120 IU, IV) or its vehicle (saline) was administered before and again in the middle of the 6-h drinking session for 5 consecutive days (total oxytocin dose of 40, 80, 160, 240 IU/day). After each 5-day treatment, baseline levels of alcohol self-administration were reestablished before the next 5-day OT treatment. In addition, the effect of OT on concurrent alcohol and IV nicotine self-administration was explored in 3 of the baboons where alcohol and nicotine were concurrently available during the 6-hr session each under an FR3 schedule for each drug. Establishment of baseline self-administration and 5-day OT treatments were completed as in the alcohol only study. There was a significant overall reduction in alcohol consumption with OT compared to placebo. On post-hoc analysis, after correcting for multiple comparisons, the 40 and 80 IU doses of OT significantly reduced alcohol consumption compared with vehicle, and consumption did not vary significantly within each 5-day treatment period. OT, qualitatively, also reduced the coadministration of both alcohol and nicotine in each baboon for at least one of the OT doses administered. These results underscore the therapeutic potential of oxytocin as a treatment of alcohol use disorder and possibly, co-use of nicotine.
Assuntos
Consumo de Bebidas Alcoólicas , Etanol , Nicotina , Ocitocina , Autoadministração , Animais , Ocitocina/administração & dosagem , Ocitocina/farmacologia , Masculino , Etanol/administração & dosagem , Nicotina/administração & dosagem , Papio , Relação Dose-Resposta a Droga , Papio anubisRESUMO
High doses of nicotine administered to rodents serve as a model for studying anxiety and test compounds' potential anxiolytic effects. At these doses, anxiety in rodents is accompanied by disruption of brain-derived neurotrophic factor (BDNF). The endocannabinoids and nicotine modulate several central nervous system processes via their specific receptors, impacting locomotion, anxiety, memory, nociception, and reward. Cannabidiol (CBD), an active ingredient of Cannabis sativa L., is devoid of psychoactive actions and has gained attention for its anxiolytic, antioxidant, and anti-inflammatory properties, among others. This work aims to examine the potential anxiety-reducing properties of CBD in a well-established experimental mouse model of anxiety-like behavior induced by high doses of nicotine on male C57BL/6 mice. In this context, the open-field behavioral test was specially conducted to assess CBD's effects on anxiety-like behavior and locomotion. Brain neuronal plasticity, modulated by BDNF, along with a diverse array of blood's metabolic markers, was examined as a means of evaluating systemic toxicity under various treatments. Finally, oxidative stress was evaluated through the measurement of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), while pro-inflammatory cytokine assessments were conducted to evaluate redox status and immune system function. Our research suggests that CBD shows potential in reducing anxiety-like behaviors induced by high doses of nicotine, by mitigating changes in BDNF protein levels in cerebral hemispheres and cerebellum. At the same time, CBD targets specific liver enzymes, maintains tissue's systemic toxicity (i.e., renal, kidney, and pancreatic), balances redox status (SOD, GSH, and MDA), and regulates the secretion of pro-inflammatory cytokines (TNF-alpha and IL-6).
Assuntos
Ansiedade , Fator Neurotrófico Derivado do Encéfalo , Canabidiol , Camundongos Endogâmicos C57BL , Nicotina , Estresse Oxidativo , Animais , Canabidiol/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Camundongos , Nicotina/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/induzido quimicamente , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Comportamento Animal/efeitos dos fármacosRESUMO
Oral nicotine pouches are the latest products in the tobacco industry. They are manufactured by large tobacco companies and entice tobacco or nicotine addicts, although the products are presented as a 'harmless choice.' Nevertheless, dentists and oral health specialists worry about oral mucosal changes due to product interactions with the oral mucosa. Unfortunately, there are no case reports of oral mucosal changes from nicotine pouches that are also investigated histopathologically. The aim of the present study was to visually and histopathologically investigate oral mucosal changes in nicotine pouch users. An online retrospective survey regarding medical and dental health, dietary habits, and tobacco consumption habits was conducted (n = 50). Respondents were selected for further intraoral and histopathological investigation based on the inclusion criteria. All five respondents had oral lesions that were histopathologically analyzed. Visually, the lesions varied in form and intensity, but all appeared white at the location where the pouches were placed. Histopathological analyses revealed parakeratosis with acanthotic epithelium, intraepithelial and connective tissue oedema, and chronic inflammatory infiltration with lymphocytes and macrophages. Participants received information about nicotine cessation and oral health recommendations. In conclusion, nicotine pouches significantly impacted oral mucosa with white lesions that revealed important changes at the cellular level.
Assuntos
Mucosa Bucal , Nicotina , Humanos , Mucosa Bucal/patologia , Mucosa Bucal/efeitos dos fármacos , Masculino , Estudos Retrospectivos , Feminino , Adulto , Pessoa de Meia-Idade , Nicotina/efeitos adversos , Doenças da Boca/induzido quimicamente , Doenças da Boca/patologia , Adulto Jovem , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversosRESUMO
This study investigates the application of an eNose (electrochemical sensory array) device as a rapid and cost-effective screening tool to detect increasingly prevalent counterfeit electronic cigarettes, and those to which potentially hazardous excipients such as vitamin E acetate (VEA) have been added, without the need to generate and test the aerosol such products are intended to emit. A portable, in-field screening tool would also allow government officials to swiftly identify adulterated electronic cigarette e-liquids containing illicit flavorings such as menthol. Our approach involved developing canonical discriminant analysis (CDA) models to differentiate formulation components, including e-liquid bases and nicotine, which the eNose accurately identified. Additionally, models were created using e-liquid bases adulterated with menthol and VEA. The eNose and CDA model correctly identified menthol-containing e-liquids in all instances but were only able to identify VEA in 66.6% of cases. To demonstrate the applicability of this model to a commercial product, a Virginia Tobacco JUUL product was adulterated with menthol and VEA. A CDA model was constructed and, when tested against the prediction set, it was able to identify samples adulterated with menthol 91.6% of the time and those containing VEA in 75% of attempts. To test the ability of this approach to distinguish commercial e-liquid brands, a model using six commercial products was generated and tested against randomized samples on the same day as model creation. The CDA model had a cross-validation of 91.7%. When randomized samples were presented to the model on different days, cross-validation fell to 41.7%, suggesting that interday variability was problematic. However, a subsequently developed support vector machine (SVM) identification algorithm was deployed, increasing the cross-validation to 84.7%. A prediction set was challenged against this model, yielding an accuracy of 94.4%. Altered Elf Bar and Hyde IQ formulations were used to simulate counterfeit products, and in all cases, the brand identification model did not classify these samples as their reference product. This study demonstrates the eNose's capability to distinguish between various odors emitted from e-liquids, highlighting its potential to identify counterfeit and adulterated products in the field without the need to generate and test the aerosol emitted from an electronic cigarette.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Técnicas Eletroquímicas/métodos , Nicotina/análise , Análise Discriminante , Aromatizantes/análise , Aromatizantes/química , Mentol/análise , Mentol/química , HumanosRESUMO
Importance: Synthetic nicotine is increasingly used in e-cigarette liquids along with flavors to appeal to youths. Regulatory loopholes have allowed tobacco manufacturers to use social media to target youths. Objective: To analyze the extent to which synthetic nicotine e-cigarette brands have implemented US Food and Drug Administration (FDA) health warning requirements and to evaluate the association between health warnings and user engagement on Instagram. Design, Setting, and Participants: In this cross-sectional study, posts from 25 brands were analyzed across a 14-month period (August 2021 to October 2022). A content analysis was paired with Warning Label Multi-Layer Image Identification, a computer vision algorithm designed to detect the presence of health warnings and whether the detected health warning complied with FDA guidelines by (1) appearing on the upper portion of the advertisement and (2) occupying at least 20% of the advertisement's area. Data analysis was performed from March to June 2024. Exposure: Synthetic nicotine e-cigarette advertisement on Instagram. Main Outcomes and Measures: The outcome variables were user engagement (number of likes and comments). Negative binomial regression analyses were used to evaluate the association between the presence and characteristics of health warnings and user engagement. Results: Of a total of 2071 posts, only 263 (13%) complied with both FDA health warning requirements. Among 924 posts with health warnings, 732 (79%) displayed warnings in the upper image portion, and 270 (29%) had a warning covering at least 20% of the pixel area. Posts with warnings received fewer comments than posts without warnings (mean [SD], 1.8 [2.5] vs 5.4 [11.7] comments; adjusted incident rate ratio [aIRR], 0.70; 95% CI, 0.57-0.86; P < .001). For posts containing warnings, a larger percentage of the warning label's pixel area was associated with fewer comments (aIRR, 0.96; 95% CI, 0.93-0.99; P = .003). Flavored posts with health warnings placed in the upper image portion received more likes than posts with warnings in the lower portion (mean [SD], 34.6 [35.2] vs 19.9 [19.2] likes; aIRR, 1.48; 95% CI, 1.07-2.06; P = .02). Conclusions and Relevance: In this cross-sectional study of synthetic nicotine brand Instagram accounts, 87% of sampled posts did not adhere to FDA health warning requirements in tobacco promotions. Enforcement of FDA compliant health warnings on social media may reduce youth engagement with tobacco marketing.
Assuntos
Publicidade , Sistemas Eletrônicos de Liberação de Nicotina , Rotulagem de Produtos , Mídias Sociais , Humanos , Estudos Transversais , Estados Unidos , Publicidade/métodos , Rotulagem de Produtos/métodos , Nicotina/efeitos adversos , United States Food and Drug AdministrationRESUMO
Early life adversity (ELA) is associated with earlier initiation and maintenance of tobacco smoking and with a greater risk of subsequent relapse. There is growing evidence that appetite hormones, including peptide YY (PYY), which modulates craving and satiety responses, play a role in stress and addiction processes. This study employed a quasi-experimental design to examine the association between ELA and circulating PYY stress responses in smokers and nonsmokers (N = 152, ages 19-73 years) to examine the effects of nicotine addiction. Smokers initiated a quit attempt as part of the study and were classified as either abstinent smokers or relapsed smokers based on their nicotine use during the follow-up period. PYY levels were measured at five timepoints during three lab sessions and compared between nonsmokers and the two smoking groups (abstainers, relapsers): while smokers were using nicotine ad libitum, 24 h after smokers initiated a quit attempt, and 4 weeks after smokers initiated a quit attempt. Multivariate analyses showed the main effects of time on PYY, which decreased over time within each session. The main effects of ELA during the first (ad libitum smoking) and second (24-h post-cessation for smokers) sessions indicated that experiencing ELA was associated with lower PYY. No systematic effect of nicotine addiction or relapse was observed in this study. These findings suggest that adults with higher ELA may experience lower PYY. Additional research is needed to further explore the role of PYY in stress and addiction processes.
Assuntos
Peptídeo YY , Recidiva , Estresse Psicológico , Tabagismo , Humanos , Peptídeo YY/sangue , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Tabagismo/psicologia , Tabagismo/sangue , Estresse Psicológico/psicologia , Estresse Psicológico/sangue , Idoso , Adulto Jovem , Abandono do Hábito de Fumar/psicologia , Experiências Adversas da Infância/psicologia , Nicotina/efeitos adversos , Fumar/psicologiaRESUMO
Sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, is characterized by brief (<2 minutes) seizures with abrupt onset and offset and stereotyped focal or generalized hypermotor events occurring predominantly (but not exclusively) from sleep. Clinically, SHE can be challenging to distinguish from psychogenic nonepileptic events or sleep disorders. Up to 30% of SHE cases are drug-resistant, and SHE represents about 10% of drug-resistant surgical epilepsy cases. Although most cases have an unknown etiology, there is a subset of individuals with pathogenic variants in the subunits of n-acetylcholine receptors (nAChR). Furthermore, some individuals with nAChR variants are responsive to nicotine. We report a case of a 23-year-old man with SHE, but no pathogenic variant on testing, whose seizures were exquisitely responsive to removal and application of a nicotine patch. This suggests an alternative mechanism of nicotine in the suppression of seizures in individuals with SHE.
Assuntos
Dispositivos para o Abandono do Uso de Tabaco , Humanos , Masculino , Adulto Jovem , Epilepsia do Lobo Frontal/tratamento farmacológico , Epilepsia do Lobo Frontal/diagnóstico , Nicotina , Eletroencefalografia , Agonistas NicotínicosRESUMO
Nicotine dependence is an important cause of excessive exposure to tobacco combustion compounds in most smokers. Nicotine replacement therapy is the main method to treat nicotine dependence, but it still has its shortcomings, such as the inability to mitigate withdrawal effects and limited applicability. It has been hypothesized that a combination of low-dose nicotine and caffeine could achieve the same psychological stimulation effect as a high dose of nicotine without causing nicotine withdrawal effects. To establish a model of nicotine dependence, male C57BL/6J mice were subcutaneously injected four times a day with nicotine (2 mg/kg) for 15 days and fed with water containing nicotine at the same time. They were randomly divided into four groups. After 24 h of withdrawal, different groups were injected with saline, nicotine (0.25 mg/kg or 0.1 mg/kg), or nicotine (0.1 mg/kg) and caffeine (20 mg/kg). Behavioral and physiological changes were evaluated by an assessment of physical signs, open field tests, elevated plus maze experiments, forced swimming tests, hot plate tests, and new-object-recognition tests. The changes in dopamine release in the prefrontal cortex (PFC) and ventral tegmental area (VTA) in the midbrain were analyzed using ELISA. The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ability and pain thresholds, reduce anxiety and depression, enhance memory and cognitive ability, and increase the level of dopamine release in the PFC and VTA. Thus, caffeine combined with nicotine has potential as a stable and effective treatment option to help humans with smoking cessation.
Assuntos
Cafeína , Camundongos Endogâmicos C57BL , Nicotina , Síndrome de Abstinência a Substâncias , Tabagismo , Animais , Cafeína/farmacologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Nicotina/farmacologia , Masculino , Camundongos , Tabagismo/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Dopamina/metabolismo , Ansiedade/tratamento farmacológico , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Modelos Animais de DoençasRESUMO
Importance: Prohibiting the sale of commonly preferred e-cigarette flavors (eg, fruity and sweet) to discourage use among youths poses a risk of diminishing efforts to decrease smoking in adults. Objective: To compare reductions in smoking achieved in adults with psychiatric conditions or lower educational level using very low nicotine content (VLNC) cigarettes alone, combined with e-cigarettes limited to tobacco flavor (TF), or combined with e-cigarettes in participant-preferred flavors. Design, Setting, and Participants: Three randomized clinical trials were conducted for 16 weeks from October 2020 through November 2023 at the University of Vermont, Brown University, and Johns Hopkins University. Participants were adults who smoked daily and were not planning to quit in the next 30 days. These participants were from 3 at-risk populations: those with affective disorders, exemplifying mental illness; those with opioid use disorder, exemplifying substance use disorders; and females of reproductive age with a high-school education or less, exemplifying lower educational level. Participants were randomly assigned to 1 of 4 experimental conditions: (1) normal nicotine content (NNC) cigarettes only; (2) VLNC cigarettes only; (3) VLNC cigarettes plus e-cigarettes with classic TF (hereafter, VLNC + TF); and (4) VLNC cigarettes plus e-cigarettes with preferred flavors (hereafter, VLNC + PF). Interventions: The NNC cigarettes contained 15.8 mg nicotine/g tobacco, the VLNC cigarettes contained 0.4 mg nicotine/g tobacco, the VLNC + TF had pods containing 5% nicotine by weight and only classic TF, and the VLNC + PF had pods containing 5% nicotine in 8 flavors (including fruity and sweet) from which participants selected 3 flavors. Main Outcomes and Measures: The primary outcome was mean total cigarettes smoked per day (CPD) during week 16. Tobacco-related biomarkers were assessed, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen. Results: A total of 326 participants (mean [SD] age, 40.09 [10.79] years; 243 females [74.5%]) from 3 randomized clinical trials were included. The VLNC cigarettes decreased total CPD, with least square (LS) means (SEMs) of 22.54 (1.59) in the NNC, 14.32 (1.32) in the VLNC, 11.76 (1.18) in the VLNC + TF, and 7.63 (0.90) in the VLNC + PF conditions. Each VLNC condition differed significantly from NNC, with an adjusted mean difference (AMD) of -8.21 (95% CI, -12.27 to -4.16; P < .001) in the VLNC, -10.78 (95% CI, -14.67 to -6.90; P < .001) in the VLNC + TF, and -14.91 (95% CI, -18.49 to -11.33; P < .001) in the VLNC + PF conditions. Participants in the VLNC + PF condition also decreased smoking below the VLNC and the VLNC + TF conditions (AMDs, -6.70 [95% CI, -9.84 to -3.55; P < .001] and -4.13 [95% CI, -7.05 to -1.21; P = .02]); the VLNC and VLNC + TF conditions did not differ significantly. Consistent with decreases in CPD, NNAL levels in the VLNC + PF condition were lower than in all other conditions, with AMDs (in pmol/mg creatinine) of -0.94 (95% CI, -1.41 to -0.47; P < .001) compared with the NNC condition, -0.47 (95% CI, -0.87 to -0.08; P = .03) compared with the VLNC condition, and -0.46 (95% CI, -0.83 to -0.10; P = .04) compared with the VLNC + TF condition. Conclusions and Relevance: These results provide further evidence that a reduced-nicotine standard for cigarettes has the potential to decrease smoking and tobacco-toxicant exposure in high-risk populations and that these effects may be enhanced when adults can access e-cigarettes in commonly preferred flavors. Trial Registration: ClinicalTrials.gov Identifiers: NCT04092387, NCT04090879, NCT04092101.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Feminino , Adulto , Masculino , Nicotina/administração & dosagem , Pessoa de Meia-Idade , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/psicologia , Produtos do Tabaco , AromatizantesRESUMO
PURPOSE: Epidemiological studies show that radon and cigarette smoke interact in inducing lung cancer, but the contribution of nicotine in response to alpha radiation emitted by radon is not well understood. MATERIALS AND METHODS: Bronchial epithelial BEAS-2B cells were either pre-treated with 2⯵M nicotine during 16â¯h, exposed to radiation, or the combination. DNA damage, cellular and chromosomal alterations, oxidative stress as well as inflammatory responses were assessed to investigate the role of nicotine in modulating responses. RESULTS: Less γH2AX foci were detected at 1â¯h after alpha radiation exposure (1-2â¯Gy) in the combination group versus alpha radiation alone, whereas nicotine alone had no effect. Comet assay showed less DNA breaks already just after combined exposure, supported by reduced p-ATM, p-DNA-PK, p-p53 and RAD51 at 1â¯h, compared to alpha radiation alone. Yet the frequency of translocations was higher in the combination group at 27â¯h after irradiation. Although nicotine did not alter G2 arrest at 24â¯h, it assisted in cell cycle progression at 48â¯h post radiation. A slightly faster recovery was indicated in the combination group based on cell viability kinetics and viable cell counts, and significantly using colony formation assay. Pan-histone acetyl transferase inhibition using PU139 blocked the reduction in p-p53 and γH2AX activation, suggesting a role for nicotine-induced histone acetylation in enabling rapid DNA repair. Nicotine had a modest effect on reactive oxygen species induction, but tended to increase alpha particle-induced pro-inflammatory IL-6 and IL-1ß (4â¯Gy). Interestingly, nicotine did not alter gamma radiation-induced γH2AX foci. CONCLUSIONS: This study provides evidence that nicotine modulates alpha-radiation response by causing a faster but more error-prone repair, as well as rapid recovery, which may allow expansion of cells with genomic instabilities. These results hold implications for estimating radiation risk among nicotine users.
Assuntos
Partículas alfa , Nicotina , Nicotina/química , Nicotina/toxicidade , DNA , Humanos , Células Epiteliais , Pulmão , Dano ao DNA , Neoplasias Pulmonares , Carcinógenos/química , Carcinógenos/toxicidade , Nitrosaminas/química , Nitrosaminas/toxicidadeRESUMO
Purpose: While previously investigating the mechanism by which atropine inhibits ocular growth, we observed that stimulation of nicotinic receptors can inhibit experimental myopia. This study expands on that preliminary finding and investigates the safety and efficacy of nicotinic stimulation in the inhibition of ocular growth. Methods: Nicotine's ability to inhibit form-deprivation myopia (FDM), following intravitreal injection (9 chicks per group) or topical application (6 chicks per group), was investigated over three doses. The ability of nicotine to inhibit lens-induced myopia (LIM) was also tested (in 12 chicks). For ocular safety, following 4 weeks of topical treatment with nicotine (n = 10), pupillary reflex, intraocular pressure, corneal curvature/thickness, lens thickness, retinal health (retinal thickness/cell apoptosis), as well as retinal function (electroretinogram recordings) were assessed. We also examined the effects of nicotine on non-ocular autonomic functions in both chicks (n = 5) and mice (n = 5). Results: Nicotine was observed to significantly inhibit the development of FDM in chicks when administered as an intravitreal injection (P < 0.05) or topical eye drops (P < 0.05), albeit not in a dose-dependent manner. Nicotine also inhibited LIM (P < 0.05) to a similar degree to that seen for FDM. Although ocular health was (for the most part) unaffected by nicotine, the highest topical dose induced a temporary reduction in cardiorespiratory output (P < 0.05). Conclusions: Nicotine, administered as an intravitreal injection or topical eye drop, significantly inhibits the development of experimental myopia. Although the anti-myopic effects observed presently are interesting, the well-reported side effects (expanded on presently) and addictive properties of nicotine would preclude its clinical use.
Assuntos
Galinhas , Modelos Animais de Doenças , Injeções Intravítreas , Miopia , Nicotina , Animais , Nicotina/administração & dosagem , Miopia/fisiopatologia , Miopia/tratamento farmacológico , Camundongos , Pressão Intraocular/efeitos dos fármacos , Agonistas Nicotínicos/administração & dosagem , Eletrorretinografia/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Relação Dose-Resposta a Droga , Masculino , Retina/efeitos dos fármacos , Refração Ocular/fisiologia , Soluções OftálmicasRESUMO
Spodoptera litura is a significant agricultural pest, and its glutathione S-transferase (GST) plays a crucial role in insecticide resistance. This study aimed to investigate the relationship between the SlGSTe11 gene of S. litura and resistance to cyantraniliprole and nicotine. Transcriptome analysis revealed that SlGSTe11 is highly expressed mainly in fat bodies, with a significant increase in SlGSTe11 gene expression under induction by cyantraniliprole and nicotine. The ectopic expression of the SlGSTe11 gene in transgenic fruit flies resulted in a 5.22-fold increase in the tolerance to cyantraniliprole. Moreover, compared to the UAS-SlGSTe11 line, the Act5C-UAS>SlGSTe11 line laid more eggs and had a lower mortality after nicotine exposure. RNAi-mediated inhibition of SlGSTe11 gene expression led to a significant increase in the mortality of S. litura under cyantraniliprole exposure. In vitro metabolism experiments demonstrated that the recombinant SlGSTe11 protein efficiently metabolizes cyantraniliprole. Molecular docking results indicated that SlGSTe11 has a strong affinity for both cyantraniliprole and nicotine. These findings suggest that SlGSTe11 is involved in the development of resistance to cyantraniliprole and nicotine in S. litura.
Assuntos
Corpo Adiposo , Glutationa Transferase , Proteínas de Insetos , Resistência a Inseticidas , Inseticidas , Nicotina , Pirazóis , Spodoptera , ortoaminobenzoatos , Animais , Spodoptera/genética , Spodoptera/efeitos dos fármacos , Spodoptera/metabolismo , Spodoptera/enzimologia , Spodoptera/crescimento & desenvolvimento , Inseticidas/farmacologia , Inseticidas/metabolismo , Inseticidas/química , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , ortoaminobenzoatos/metabolismo , ortoaminobenzoatos/farmacologia , Pirazóis/farmacologia , Nicotina/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Glutationa Transferase/química , Resistência a Inseticidas/genética , Corpo Adiposo/metabolismo , Corpo Adiposo/enzimologia , Corpo Adiposo/efeitos dos fármacos , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: Electronic cigarettes have gained popularity as a nicotine delivery system, which has been recommended by some as an aid to help people quit traditional smoking. The potential long-term effects of vaping on the cardiovascular system, as well as how their effects compare with those from standard cigarettes, are not well understood. The intrinsic frequency (IF) method is a systems approach for analysis of left ventricle and arterial function. Recent clinical studies have demonstrated the diagnostic and prognostic value of IF. Here, we aim to determine whether the novel IF metrics derived from carotid pressure waveforms can detect effects of nicotine (delivered by chronic exposure to electronic cigarette vapor or traditional cigarette smoke) on the cardiovascular system. METHODS AND RESULTS: One hundred seventeen healthy adult male and female rats were exposed to purified air (control), electronic cigarette vapor without nicotine, electronic cigarette vapor with nicotine, and traditional nicotine-rich cigarette smoke, after which hemodynamics were comprehensively evaluated. IF metrics were computed from invasive carotid pressure waveforms. Standard cigarettes significantly increased the first IF (indicating left ventricle contractile dysfunction). Electronic cigarettes with nicotine significantly reduced the second IF (indicating adverse effects on vascular function). No significant difference was seen in the IF metrics between controls and electronic cigarettes without nicotine. Exposure to electronic cigarettes with nicotine significantly increased the total IF variation (suggesting adverse effects on left ventricle-arterial coupling and its optimal state), when compared with electronic cigarettes without nicotine. CONCLUSIONS: Our IF results suggest that nicotine-containing electronic cigarettes adversely affect vascular function and left ventricle-arterial coupling, whereas standard cigarettes have an adverse effect on left ventricle function.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotina , Animais , Masculino , Nicotina/administração & dosagem , Nicotina/efeitos adversos , Nicotina/toxicidade , Feminino , Vaping/efeitos adversos , Vapor do Cigarro Eletrônico/efeitos adversos , Ratos , Função Ventricular Esquerda/efeitos dos fármacos , Ratos Sprague-Dawley , Agonistas Nicotínicos/administração & dosagem , Agonistas Nicotínicos/toxicidade , Agonistas Nicotínicos/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Produtos do Tabaco/efeitos adversosRESUMO
BACKGROUND: The Omnibus Budget Bill, known as H. R. 2471, passed through Congress on March 10, 2022, and was eventually signed by President Biden on March 15, 2022. This bill amended the Federal Food, Drug, and Cosmetic Act granting the Food and Drug Administration (FDA) regulatory authority over synthetic nicotine. OBJECTIVE: This study aims to examine the public perceptions of the Omnibus Bill that regulates synthetic nicotine products as tobacco products on Twitter (rebranded as X). METHODS: Through the X streaming application programming interface, we collected and identified 964 tweets related to the Omnibus Bill on synthetic nicotine between March 8, 2022, and April 13, 2022. The longitudinal trend was used to examine the discussions related to the bill over time. An inductive method was used for the content analysis of related tweets. By hand-coding 200 randomly selected tweets by 2 human coders respectively with high interrater reliability, the codebook was developed for relevance, major topics, and attitude to the bill, which was used to single-code the rest of the tweets. RESULTS: Between March 8, 2022, and April 13, 2022, we identified 964 tweets related to the Omnibus Bill regulating synthetic nicotine. Our longitudinal trend analysis showed a spike in the number of tweets related to the bill during the immediate period following the bill's introduction, with roughly half of the tweets identified being posted between March 8 and 11, 2022. A majority of the tweets (497/964, 51.56%) had a negative sentiment toward the bill, while a much smaller percentage of tweets (164/964, 17.01%) had a positive sentiment toward the bill. Around 31.43% (303/964) of all tweets were categorized as objective news or questions about the bill. The most popular topic for opposing the bill was users believing that this bill would lead users back to smoking (145/497, 29.18%), followed by negative implications for small vape businesses (122/497, 24.55%) and government or FDA mistrust (94/497, 18.91%). The most popular topic for supporting the bill was that this bill would take a dangerous tobacco product targeted at teens off the market (94/164, 57.32%). CONCLUSIONS: We observed a more negative sentiment toward the bill on X, largely due to users believing it would lead users back to smoking and negatively impact small vape businesses. This study provides insight into public perceptions and discussions of this bill on X and adds valuable information for future regulations on alternative nicotine products.
Assuntos
Nicotina , Opinião Pública , Mídias Sociais , United States Food and Drug Administration , Humanos , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudênciaRESUMO
BACKGROUND: The Australian National Perinatal Data Collection collates all live and stillbirths from States and Territories in Australia. In that database, maternal cigarette smoking is noted twice (smoking <20 weeks gestation; smoking >20 weeks gestation). Cannabis use and other forms of nicotine use, for example vaping and nicotine replacement therapy, are nor reported. The 2021 report shows the rate of smoking for Australian Indigenous mothers was 42% compared with 11% for Australian non-Indigenous mothers. Evidence shows that Indigenous babies exposed to maternal smoking have a higher rate of adverse outcomes compared to non-Indigenous babies exposed to maternal smoking (S1 File). OBJECTIVES: The reasons for the differences in health outcome between Indigenous and non-Indigenous pregnancies exposed to tobacco and nicotine is unknown but will be explored in this project through a number of activities. Firstly, the patterns of parental and household tobacco, nicotine and cannabis use and exposure will be mapped during pregnancy. Secondly, a range of biological samples will be collected to enable the first determination of Australian Indigenous people's nicotine and cannabis metabolism during pregnancy; this assessment will be informed by pharmacogenomic analysis. Thirdly, the pharmacokinetic and pharmacogenomic findings will be considered against maternal, placental, foetal and neonatal outcomes. Lastly, an assessment of population health literacy and risk perception related to tobacco, nicotine and cannabis products peri-pregnancy will be undertaken. METHODS: This is a community-driven, co-designed, prospective, mixed-method observational study with regional Queensland parents expecting an Australian Indigenous baby and their close house-hold contacts during the peri-gestational period. The research utilises a multi-pronged and multi-disciplinary approach to explore interlinked objectives. RESULTS: A sample of 80 mothers expecting an Australian Indigenous baby will be recruited. This sample size will allow estimation of at least 90% sensitivity and specificity for the screening tool which maps the patterns of tobacco and nicotine use and exposure versus urinary cotinine with 95% CI within ±7% of the point estimate. The sample size required for other aspects of the research is less (pharmacokinetic and genomic n = 50, and the placental aspects n = 40), however from all 80 mothers, all samples will be collected. CONCLUSIONS: Results will be reported using the STROBE guidelines for observational studies. FORWARD: We acknowledge the Traditional Custodians, the Butchulla people, of the lands and waters upon which this research is conducted. We acknowledge their continuing connections to country and pay our respects to Elders past, present and emerging. Notation: In this document, the terms Aboriginal and Torres Strait Islander and Indigenous are used interchangeably for Australia's First Nations People. No disrespect is intended, and we acknowledge the rich cultural diversity of the groups of peoples that are the Traditional Custodians of the land with which they identify and with whom they share a connection and ancestry.