O Papel bidirecional da nicotina na tarefa Go/No-go: um ensaio clínico piloto / The bidirectional role of nicotine in a Go/No-go task: a pilot clinical trial / El papel bidireccional de la nicotina en la tarea Go/no-go: un ensayo clínico piloto

Estudos mostram que o tabagismo é responsável por afetar algumas funções cognitivas. No entanto, a nicotina é apenas um dos componentes existentes no cigarro e existem evidências de que pode servir como agente neuroprotetivo e causar melhoras em algumas funções cognitivas. O objetivo desta pesquisa foi investigar como a nicotina interage com algumas funções cognitivas. Um ensaio clínico piloto com administração de gomas de nicotina contendo 2-mg ou 4-mg, ou gomas placebo contendo a mesma textura, sabor e aparência, foi realizado. Quarenta e dois participantes participaram da pesquisa e os resultados indicaram que a relação entre nicotina e o desempenho na tarefa Go/No-Go podem ser bidirecionais. Os resultados indicaram que participantes do grupo que utilizaram 4-mg de nicotina apresentaram menor desempenho, enquanto os participantes que fizeram uso de 2-mg de nicotina tiveram melhor desempenho do que os demais. Esta pesquisa tem aplicações biopsicossociais e podem ajudar na compreensão da relação entre tabagismo e nicotina, além de contribuir para estratégias que possam ajudar no abandono do cigarro ou na melhora de condições que afetem a cognição (AU).

Past findings in the literature indicated that smoking could affect given cognitive functions. However, nicotine is only one of the components in cigarettes and there is evidence that it may act as a neuroprotective agent and improve some cognitive functions. The purpose of this research was to investigate how nicotine interacts with certain cognitive functions. We conducted a pilot clinical trial using nicotine gum containing 2-mg or 4-mg, or placebo gum with the same texture, flavor, and appearance. Forty-two healthy nonsmokers were enrolled in this research. Our findings indicated that the relationship between nicotine and performance on the Go/No-Go task might be opposite. The results showed that participants in the 4-mg group performed worse, while participants who used 2-mg of nicotine performed better than the others. This research supports biopsychosocial applications and can help interpret the relationship between smoking and nicotine, and contribute to strategies that may support smoking cessation, or improve conditions that affect cognition (AU).

Estudios demuestran que el tabaquismo es responsable de afectar a algunas funciones cognitivas. Sin embargo, la nicotina es solo uno de los componentes de los cigarrillos, y existen evidencias de que la nicotina puede actuar como un agente neuroprotector y mejorar algunas funciones cognitivas. El objetivo de este estudio fue investigar cómo la nicotina interactúa con algunas funciones cognitivas. Se realizó un ensayo clínico piloto con la administración de chicles de nicotina de 2 mg o 4 mg, o chicles de placebo con la misma textura, sabor y apariencia. Cuarenta y dos participantes participaron en la investigación y los resultados indicaron que la relación entre la nicotina y el rendimiento en la tarea Go/No-go puede ser bidireccional. Los resultados indicaron que los participantes del grupo de 4 mg obtuvieron un menor rendimiento en las variables del Go/No-Go, mientras que los participantes que utilizaron 2 mg de nicotina obtuvieron un mejor rendimiento que los demás. Esta investigación respalda las aplicaciones biopsicosociales y puede ayudar a interpretar la relación entre el tabaquismo y la nicotina, además de contribuir a las estrategias que pueden ayudar a dejar de fumar o mejorar las condiciones que afectan la cognición (AU).

Avaliação da influência da Coenzima Q10 sobre o processo de reparo periimplantar de implantes instalados em tíbias de ratos expostos ou não à nicotina / Evaluation of the influence of Coenzyme Q10 on the periimplant repair processo of implants installed in the tíbias of rats exposed or not to nicotine

O propósito do presente estudo foi avaliar a influência da Coenzima Q10 (CoQ10) no reparo periimplantar em implantes instalados em tíbias de ratos modificados sistemicamente ou não pela nicotina. Oitenta ratos machos (Wistar), foram divididos em quatro grupos (n=20). No dia 0 os animais receberam um implante (4 x 2,2mm ­ SLA) na metáfise proximal das tíbias direita e esquerda. Nos 30 dias que antecedem o procedimento cirúrgico e nos 28 que o sucedem, os animais receberam duas injeções subcutâneas diárias de 3mg/kg de hemissulfato de nicotina ou solução salina na região dorsal, com 12 horas de intervalo entre elas. Logo após à cirurgia, o protocolo se constituiu na administração via gavagem gástrica de 1 ml de glicerina vegetal, ou suplementação diária com 120 mg de CoQ10, ambos até o final do experimento. SS (SHAM): o protocolo de aplicação utilizado foi o de solução salina subcutânea, e os animais receberam gavagem gástrica diária de 1 ml de glicerina vegetal. SS-CoQ10: o protocolo de aplicação utilizado foi o de solução salina subcutânea e, como suplementação, receberam 120 mg de Coenzima Q10 via gavagem gástrica. NIC: o protocolo de aplicação utilizado foi o de nicotina, e os animais receberam gavagem gástrica diária de 1 ml de glicerina vegetal. NIC-CoQ10: o protocolo de aplicação utilizado foi o de nicotina e, como suplementação, os animais receberam 120 mg de CoQ10 via gavagem gástrica. As eutanásias foram aos 7 e 28 dias pós-operatórios. As peças coletadas foram processadas com desmineralização para as análises histológica, histométrica (PTON) e imunoistoquímica para detecção de BMP/2, OCN e TRAP; e sem desmineralização para análise da área do contato direto osso/implante (BIC). Após análise de normalidade e homocedasticidade, os dados foram submetidos aos testes mais adequados com significância de 5% (p≤0,05). Com relação ao contato osso implante, o grupo SS, SS-Q10 e NIC- Q10, apresentaram maior BIC em todos os períodos experimentais quando comparado com o grupo NIC. Os grupos SS, SS-Q10 e NIC-Q10 apresentaram também maior PTON em todos os períodos experimentais quando comparado com o grupo NIC. A análise histológica dos tecidos periimplantares mostrou que o grupo NIC-Q10 apresentou características histológicas que se mostraram similares ao grupo controle, no entanto, com maior quantidade de tecido ósseo periimplantar e menor quantidade de tecido conjuntivo. Nos padrões de marcação imunoistoquímica, quando comparado ao grupo SS, o grupo NIC-Q10 apresentou menor imunomarcação para e OCN, menor marcação para TRAP e não houve diferenças quanto a marcação de BMP2. Dentro dos limites do presente estudo, pode-se concluir que a Coenzima Q10 exerceu uma influência positiva na remodelação óssea periimplantar em implantes osseointegrados(AU)

The purpose of the presente study was to evaluate the influence of Coenzyme Q10 (CoQ10) on periimplant repair in implants installed in the tíbia of rats modificated sistemically or not by nicotine. Eighty male rats (Wistar) were divided into four groups(n=20). On day 0 the animals received na implant (4x2,2mm-SLA) in the proximal metaphasys of the right and left tíbias. In the 30 days preceding the surgical procedure and the 28 days following it, the animals received two daily subcutaneous injections of 3 mg/kg of nicotine hemissulfate or saline solution in the dorsal region, with a 12-hour interval between them. Soon after surgery, the protocol consisted of the administration via gastric gavage of 1ml of vegetable glycerin, or daily supplementation with 120 mg of CoQ10, both until the endo f of the experiment. SS (SHAM): the application protocol used was subcutaneous saline solution, and the animals received daily gastric gavage of 1 ml of vegetal glycerin. SS-CoQ10: the application protocol used was subcutaneous saline solution and, as a supplement, they received 120 mg of Coenzyme Q10 via gastric gavage. NIC: the application protocol used was nicotine, and the animals received daily gastric gavage of 1 ml of vegetable glycerin. NIC-CoQ10: the application protocol used was nicotine and, as a supplement, the animals received 120 mg of CoQ10 via gastric gavage. Euthanasias were performed at 7 and 28 days after surgery. The colleted pieces were processed with desmineralization for histological analysis, área of neofomad bone tissue, histomorfometric analysis (PTON) and immunohistochemistry for the detection of BMP2, OCN and TRAP; and without desmineralization for direct bone/implant contat (BIC) analysis. Regarding bonéimplant contact, the SS, SS-Q10 and NIC-Q10 groups showed higher BIC in all experimental periods When compared to the NIC group. The histological analysis of the periimplant tissues showed that the NIC-Q10 group presented histological characteristics that were similar to the control group, however, with a greater amount of periimplant bone tissue and less connective tissue. In immunohistochemical staining patterns, when compared to the SS group, the NICQ10 group showed lower immunostaining for and OCN, lower staining for TRAP and there were no diferences regarding BMP2 staining. Within the limits of the presente study, it can be concluded that Coenzyme Q10 exerted a positive influence on periimplant bone remodeling in osseointegrated implants(AU)

Evaluation of Lung Volume and Effect of Vital Staining as Motivation to Quit Tobacco among Nicotine Dependents of Kanpur, India

Abstract Objective: To quantify and compare respiratory functions and further screen the oral mucosa of tobacco and non-tobacco users. Material and Methods: First control group, non-tobacco users (n=55); Second group, smokers' group (n=168) who currently smoked cigarettes; Third group smokeless/chewing type, tobacco group (n=81); Fourth group, both smokeless and smoking type tobacco users (n=46). Fagerstrom Test for Nicotine Dependences (FTND) and Fagerström Test for Nicotine Dependence-Smokeless Tobacco (FTND-ST) instruments were used to assess nicotine dependence. Subsequently, spirometry and Toluidine Blue (TB) vital staining were performed. Chi-squared and one-way analysis of variance (ANOVA) were used for statistical analysis. Results: Fagerstrom test resulted in 48.8% of subjects with low dependency, followed by an increase in nicotine dependency from low to moderate (29.2%), moderate (15.6%), and highly dependent (6.4%) groups. All respiratory function tests and oral screening confirmed significant changes amongst tobacco and non-tobacco users. The forced vital capacity of non-smoker group was significantly different from other tobacco users' group (p<0.05). Conclusion: Early effects of tobacco use can lead to complications with the respiratory system and oral cavity. Such data can be used to delineate the harm of tobacco and should be used to urge individuals to evade the utilization of tobacco (AU).

Impacts of nicotine metabolite rate and acupuncture frequency on smoking cessation: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the efficacy of different acupuncture frequencies in tobacco-dependent patients and explore the impact of nicotine metabolite rate (NMR) on smoking cessation in the intervention with acupuncture.@*METHODS@#A total of 120 cases of tobacco-dependent patients were randomly divided into a high-frequency group (60 cases, 12 cases dropped off) and a low-frequency group (60 cases, 6 cases dropped off). In the two groups, smoking cessation counseling was provided prior to acupuncture. Acupuncture was applied to Baihui (GV 20), Lieque (LU 7), Zusanli (ST 36), etc. Additionally, electric stimulation was added at Lieque (LU 7) and Zusanli (ST 36), with continuous wave, 15 Hz in frequency. The duration of treatment was 8 weeks in either group. In the high-frequency group, the treatment was given 5 times weekly from week 1 to week 4, and was 3 times weekly from week 5 to week 8. In the low-frequency group, the treatment was given 3 times weekly from week 1 to week 4, and was twice a week from week 5 to week 8. The immediate withdrawal rate, persistent withdrawal rate, the score of Fagerstrőm test for nicotine dependence (FTND) before and after treatment, as well as the score of Minnesota nicotine withdrawal scale (MNWS) in 1 and 8 weeks of treatment were compared among the patients with high and low NMR between the two groups separately. The Logistic regression analysis was used to screen the influencing factors of smoking cessation in the intervention with acupuncture.@*RESULTS@#After treatment, there was no statistical significance of the differences in the immediate withdrawal rate (35.4% [17/48] vs 29.6% [16/54]) and the persistent withdrawal rate (33.3% [16/48] vs 25.9% [14/54]) between the high-frequency group and the low-frequency group (P>0.05). The difference in withdrawal rate had no statistical significance between high and low NMR patients (P>0.05). FTND scores after treatment were lower than those before treatment (P<0.01) and MNWS scores were lower than those in 1 week of treatment (P<0.01) in the two groups. However, the differences had no statistical significance between the two groups and between the patients with high NMR and low NMR (P>0.05). Age, education level and NMR were the influencing factors of smoking cessation in the intervention with acupuncture (P<0.05).@*CONCLUSION@#Acupuncture with different frequencies has no obvious impact on the efficacy in tobacco-dependent patients. The lower nicotine metabolite rate in individuals, the better efficacy of acupuncture. The smokers with high nicotine metabolite rate may obtain a better effect of cessation in the high-frequency intervention with acupuncture.

Intercambio desde los cigarrillos convencionales a los sistemas electrónicos de administración de nicotina: revisión sistemática rápida con metaanálisis y aspectos económicos / Switching from cigarettes to electronic nicotine delivery system: rapid systematic review and meta-analysis and economic aspects

RESUMEN Objetivos. Evaluar cómo y en qué medida se produce un intercambio desde los cigarrillos convencionales (CC) a los sistemas electrónicos de administración de nicotina (SEAN). Materiales y métodos. Se realizó una revisión sistemática hasta agosto de 2019. El desenlace primario fue la proporción de un intercambio completo o parcial de CC a los SEAN y sus aspectos económicos. Los desenlaces secundarios como medidas de resultado fueron la probabilidad de intercambio y la tendencia en el intercambio por países. Resultados. Se encontraron 3628 referencias y se incluyeron 49 estudios con datos epidemiológicos y económicos. Los estudios económicos sobre la elasticidad cruzada de precios mostraron que los CC son parcialmente intercambiables por SEAN. La mayoría de los estudios reportaron que la prevalencia del consumo de cigarrillos electrónicos se incrementó con el tiempo. Tres estudios reportaron una reducción significativa de los CC consumidos por día entre fumadores duales (convencionales más SEAN) en comparación con los consumidores de CC. El odds ratio ajustado y combinado de dejar los CC entre consumidores de SEAN en comparación con quienes nunca consumieron o lo hicieron en el pasado fue de 1,19 (IC95%: 1,09-1,30; heterogeneidad 0%). Los estudios longitudinales mostraron una creciente prevalencia del uso de cigarrillos electrónicos, principalmente en adolescentes. Se encontró una relación negativa entre el consumo y aumento de precio de CC y electrónicos. Conclusión. La probabilidad de dejar de fumar CC entre consumidores habituales de SEAN se incrementó respecto a los consumidores que nunca o que solían consumir SEAN. Estudios económicos reportaron que los cigarrillos electrónicos son parcialmente intercambiables por los CC.

ABSTRACT Objectives. To assess how and in what extent the electronic nicotine delivery systems (ENDS) use substituted the consumption of traditional combustible cigarettes (c-cigarettes, c-cig). Materials and Methods. We performed a systematic review of the literature up to August 2019 in scientific databases. Primary outcomes were proportion of complete or partial substitution of conventional to electronic cigarettes and related economic aspects. Secondary outcomes were odds ratio of substitution and country-wise time trends. Results. We retrieved 3,628 references and included 49 studies, providing economic and epidemiological data. Economic studies of cross-price elasticity showed that combustible cigarettes are partially substitutable for electronic cigarettes. Most studies reported that electronic cigarettes consumption prevalence increased over time. Three studies reported a significant reduction of combustible cigarettes consumed per day among dual users (combustible- plus electronic- cigarettes users) versus combustible-cigarettes users. The pooled adjusted odds ratio of quitting combustible cigarettes among electronic cigarettes users versus never or past electronic cigarettes (e-cigarettes, e-cig) users was 1.19 (95% confidence interval 1.09 to 1.30; heterogeneity score 0%). Longitudinal studies showed globally a growing prevalence of electronic cigarettes use, mainly in adolescents. A negative relationship between consumption and price increase of electronic and combustible cigarettes was found. Conclusion. The chance of quitting smoking combustible cigarettes among current electronic nicotine delivery systems users was increased with respect to never- or past- electronic nicotine delivery systems users. Economic studies reported that electronic cigarette is partially substitutable for combustible cigarettes.

La administración de nicotina aguda retarda la extinción en automoldeamiento pavloviano: un estudio preliminar / Acute nicotine administration retards extinction from pavlovian autoshaping: A preliminary study

Resumen Introducción y objetivo: Los procesos de aprendizaje y motivación han sido centrales para la comprensión de los mecanismos que subyacen al tabaquismo. En particular, existe evidencia creciente sobre la importancia de valores motivacionales de incentivo para entender el inicio y mantenimiento del tabaquismo. El objetivo general de este experimento fue evaluar el papel de la nicotina aguda sobre el valor de incentivo de una recompensa natural, (comida) asociada con un estímulo ambiental, (palanca experimental). Método: Se utilizaron ratas Wistar. Se administró nicotina (0.4 mg/kg) de manera aguda en momentos específicos del entrenamiento, utilizando un procedimiento de diez sesiones de adquisición y cuatro sesiones extinción en una tarea pavloviana de automoldeamiento. El diseño experimental incluyó tres grupos, el grupo control de solución salina y grupos de nicotina durante la adquisición y la extinción. Resultados: Se encontró que la administración aguda de nicotina, de manera específica y en comparación con los otros dos grupos experimentales, resultó en un efecto de retardo durante la fase de extinción, y que una administración similar de nicotina no resultó en efectos observables durante el desempeño comportamental en adquisición. Conclusiones: Estos resultados apoyan el papel de la nicotina como fortalecedora del valor de incentivo de las claves ambientales durante la extinción para una tarea de automoldeamiento.

Abstract Introduction and goal: Learning and motivational processes have been central for a modern understanding of tobacco addiction. There is evidence that supports the importance of incentive motivational processes for the maintenance of tobacco addiction. The main goal of the present experiment was to evaluate the effects of acute nicotine on the incentive value of a natural reward, (food) paired with an environmental cue (pressing lever). Method: Wistar rats were used. Accute nicotine (0.4 mg/kg) was administered on key sessions, using a pavlovian autoshaping procedure involving ten acquisition and four extinction sessions. The experimental design included three groups, a saline administration control group and groups with specific nicotine administration during either acquisition or extinction. Results: We found that acute administration of nicotine, in contrast with saline only or previous nicotine administration during acquisition, had an enhancing effect on responding for the environmental cue during autoshaping extinction, but we did not find evidence that acute nicotine affected acquisition performance. Conclusion: Our results are consistent with a role of nicotine enhancing the incentive value of stimuli during extinction from a pavlovian autoshaping task.

Grau de dependência à nicotina de pacientes atendidos para tratamento do tabagismo em universidade pública / Nicotine dependence degree of patients treated for smoking addiction at a public university / Grado de dependencia a la nicotina de pacientes tratados por fumar en una universidad pública

OBJETIVO: identificar o grau de dependência à nicotina e dados sociodemográficos segundo o gênero dos pacientes atendidos pelo projeto de extensão Educando e Tratando o Tabagismo promovido por uma universidade pública. MÉTODO: estudo transversal, com dados provenientes de 361 prontuários de pacientes que participantes do projeto no período de 2014 a 2018. Realizou-se o teste de Fagerström, por meio do qual classificou-se os pacientes com grau de dependência: muito baixo, baixo, médio, elevado e muito elevado de acordo com a soma dos pontos obtidos nas questões aplicadas. RESULTADOS: a predominância no grau de dependência a nicotina foi observada no sexo feminino com maiores percentuais de classificação para dependência elevada e muito elevada, 33,5% e 25,3% respectivamente. Entre os homens verificou-se grau de dependência elevado 28,1% e baixo 21,9%. Contatou-se que o grau de dependência química a nicotina esteve associada a dependência física (valor-p=0,002) e psicológica (valor-p=0,003). CONCLUSÃO: a evidência de maior frequência de indivíduos com alto grau de dependência química à nicotina demonstra a importância da associação de terapias medicamentosas com abordagens cognitivas comportamentais por meio de intervenções de enfermagem, relacionadas ao controle e cessação do tabagismo por meio da educação em saúde.

OBJECTIVE: to identify the nicotine dependence degree and sociodemographic data according to the gender of the patients assisted by the Educating and Treating Smoking extension project promoted by a public university. METHOD: a cross-sectional study, with data from 361 medical records of patients participating in the project from 2014 to 2018. The Fagerström test was performed, through which patients with a degree of dependence were classified as follows: very low, low, medium, high, and very high, according to the sum of the points obtained in the applied questions. RESULTS: predominance in the nicotine dependence degree was observed in women with higher percentages of classification for high and very high dependence, 33.5% and 25.3% respectively. Among men, a high degree of dependence was found to be 28.1% and low, 21.9%. It was found that the degree of chemical dependence on nicotine was associated with physical (p-value = 0.002) and psychological (p-value = 0.003) dependence. CONCLUSION: the evidence for a higher frequency of individuals with a high chemical dependence degree for nicotine demonstrates the importance of combining drug therapies with cognitive behavioral approaches through Nursing interventions, related to controlling and quitting the smoking addiction through health education.

OBJETIVO: identificar el grado de dependencia a la nicotina y los datos sociodemográficos según el género de los pacientes atendidos por el proyecto de extensión Educar y tratar el tabaquismo promovido por una universidad pública. MÉTODO: estudio transversal, con datos de 361 registros médicos de pacientes que participaron en el proyecto de 2014 a 2018. Se realizó la prueba de Fagerström, a través de la cual se clasificaron los pacientes con un grado de dependencia: muy bajo, bajo, medio, alto y muy alto de acuerdo con la suma de los puntos obtenidos en las preguntas aplicadas. RESULTADOS: el predominio en el grado de dependencia a la nicotina se observó en mujeres con porcentajes más altos de clasificación de dependencia alta y muy alta, 33.5% y 25.3% respectivamente. Entre los hombres, se encontró un alto grado de dependencia del 28,1% y bajo del 21,9%. Se encontró que el grado de dependencia química de la nicotina se asoció con el físico (valor p = 0.002) y psicológico (valor p = 0.003). CONCLUSIÓN: la evidencia de una mayor frecuencia de individuos con un alto grado de dependencia química de la nicotina demuestra la importancia de combinar las terapias farmacológicas con enfoques cognitivos conductuales a través de intervenciones de enfermería, relacionadas con el control del tabaquismo y la cesación a través de la educación sanitaria.

Cigarro Eletrônico: Mocinho ou vilão? / Cigarrillo Electrónico: ¿Bueno o malo? / Electronic Cigarette: Good guy or bad guy?

RESUMEN Objetivo: Discutir los efectos sobre la salud causados por el uso de cigarrillos electrónicos. Material y métodos: Para ello, se realizó una búsqueda en la base de datos PubMed/Medline de artículos completos publicados en los últimos 10 años. Se utilizaron un total de 21 artículos, según los criterios de inclusión establecidos, con mayor prevalencia de estudios transversales. Resultados: Se encontró que los cigarrillos electrónicos pueden incluso ayudar en el cese del tabaquismo convencional, sin embargo, sus usuarios no están exentos de sufrir complicaciones de salud sistémicas. Estos contienen sustancias tóxicas y no deben considerarse completamente seguros e inofensivos. Conclusiones: se necesitan más estudios para determinar las implicaciones para la salud a largo plazo del uso de este deben considerarse completamente seguros e inofensivos.

SUMMARY Objective: to discuss the health effects caused by the use of electronic cigarettes. Material and Methods : A search was performed in the PubMed/Medline database of complete articles published in the last 10 years. A total of 21 articles were used, according to the established inclusion criteria, with a higher prevalence of cross-sectional studies. Results: It was verified that electronic cigarettes may even help in the cessation of conventional smoking, however, their users are not exempt from suffering systemic health complications. They present toxic substances and should not be considered totally safe and harmless. Conclusions : Further studies are still needed to determine the implications of the use of this electronic device on the health of its users in the long term.

Central neural mechanism of increased pain sensitivity induced by nicotine abstinence / 生理学报

Nicotine is the main addictive component in cigarettes that motivates dependence on tobacco use for smokers and makes it difficult to quit through regulating a variety of neurotransmitter release and receptor activations in the brain. Even though nicotine has an analgesic effect, clinical studies demonstrated that nicotine abstinence reduces pain threshold and increases pain sensitivity in smoking individuals. The demand for opioid analgesics in nicotine abstinent patients undergoing surgery has greatly increased, which results in many side effects, such as nausea, vomiting, and respiratory depression, etc. In addition, these side effects would hinder patients' physical and psychological recovery. Therefore, identifying the neural mechanism of the increase of pain sensitivity induced by nicotine abstinence and deriving a way to cope with the increased demand for postoperative analgesics would have enormous basic and clinical implications. In this review, we first discussed different experimental pain stimuli (e.g., cold, heat, and mechanical pain)-induced pain sensitivity changes after a period of nicotine dependence/abstinence from both animal and human studies. Then, we summarized the effects of the brain neurotransmitter release (e.g., serotonin, norepinephrine, endogenous opioids, dopamine, and γ-aminobutyric acid) and their corresponding receptor activation changes after nicotine abstinence on pain sensitivity. Finally, we discussed the limits in recent studies. We proposed that more attention should be paid to human studies, especially studies among chronic pain patients, and functional magnetic resonance imaging might be a useful tool to reveal the mechanisms of abstinence-induced pain sensitivity changes. Besides, considering the influence of duration of nicotine dependence/abstinence and gender on pain sensitivity, we proposed that the effects of nicotine abstinence and individual differences (e.g., duration of abstinence from smoking, chronic/acute abstinence, and gender) on abstinence-induced pain sensitivity should be fully considered in formulating pain treatment protocols. In summary, this paper could deepen our understanding of nicotine abstinence-induced pain sensitivity changes and its underlying neural mechanism, and could also provide effective scientific theories to guide clinical pain diagnosis and treatment, which has important clinical significance.

Efeito da exposição a produtos fumígenos sobre a expressão de metalotioneínas durante a artrite experimental e sobre linfócitos T / Effect of exposure to tobacco-related products on metallothionein expression in the experimental arthritis and on T lymphocytes functions

Produtos liberados pela queima do cigarro convencional (CC) estão relacionados com a progressão clínica da artrite reumatoide (AR). Produtos fumígenos não combustíveis surgiram com a premissa de apresentarem menor toxicidade que o CC, dentre os quais está o tabaco aquecido (heat-not-burn tobacco; HNBT). Neste projeto investigamos os efeitos do HNBT sobre eventos envolvidos na AR, focando na sintomatologia, expressão de metalotioneínas (MTs), e na biologia de linfócitos T CD4+ primários e da linhagem Jurkat. Exposições in vivo ao ar, CC ou HNBT foram realizadas 2 vezes ao dia, 1 hora cada (12 CC ou 24 HNBT/hora), nos dias 14-21 da indução da artrite induzida por antígeno (AIA) em camundongos C57Bl/6. Foram realizadas análises dos parâmetros clínico da doenças, histopatologia e imunohistoquímica; quantificação de nicotina e cotinina séricas por cromatografia líquida acoplada a espectrometria de massas (MS). Os efeitos das exposições in vitro sobre linfócitos T foram mensurados por citometria de fluxo e ELISA. A concentração de metais emitidas pelo CC ou HNBT durante as exposições foram mensurados por MS com plasma acoplado. Camundongos expostos ao CC apresentaram intensa inflamação pulmonar, expressões acentuadas de MTs hepáticas e pulmonares e exacerbação dos parâmetros de AIA quando comparados ao grupo expostos ao HNBT. Animais expostos ao CC ou ao HNBT apresentaram redução na celularidade de órgãos linfoides. Somente a exposição in vitro ao CC causou estresse oxidativo e secreção de citocinas inflamatórias, ativação do receptor de hidrocarbonetos arila (AhR) e polarização de células Th17. Diferentemente, exposição ao CC ou ao HNBT provocaram redução da secreção de IL-2 e proliferação de células Jurkat. A exposição de células Jurkat à nicotina mimetizou os efeitos inibitórios da exposição ao HNBT sobre a secreção de IL-2 e proliferação de linfócitos T. O CC liberou maiores concentrações de metais nas câmaras de exposição. Associados, nossos resultados mostram que embora exposições ao HNBT não exacerbem parâmetros inflamatórios de AIA e nem em funções linfócitos T, ambos produtos prejudicam a celularidade de órgãos linfoides e a proliferação e secreção de IL-2 por linfócitos T

Products released by burning conventional cigarettes (CC) are related to the worsening of rheumatoid arthritis (RA). Non-combustible smoking products appeared with the premise of presenting less toxicity than the CC, among which is the heated tobacco (heat-not-burn tobacco; HNBT). Here, we investigate the effects of HNBT on events involved in RA, focusing on symptoms, expression of metallothioneins (MTs), and on the biology of primary CD4+ T lymphocytes and the Jurkat T cell lineage. In vivo exposures to air, CC or HNBT were performed twice a day, 1 hour each (12 CC or 24 HNBT / hour), on days 14-21 of the induction of antigen-induced arthritis (AIA) in C57Bl / 6 mice. Analyzes of the clinical parameters of the AIA, histopathology, and immunohistochemistry were performed; quantification of nicotine and cotinine by liquid chromatography coupled to mass spectrometry (MS). The in vitro effects of exposures on T lymphocytes were measured by flow cytometry and ELISA. The concentration of metals released by the CC or HNBT during the exposures was measured by MS with coupled plasma. Mice exposed to CC showed intense pulmonary inflammation, marked expressions of hepatic and pulmonary MTs, and exacerbation of AIA parameters when compared to the group exposed to HNBT. Animals exposed to CC or HNBT showed a reduction in the cellularity of lymphoid organs. Only in vitro exposure to CC caused oxidative stress and secretion of inflammatory cytokines, activation of the aryl hydrocarbon receptor (AhR), and polarization of Th17 cells. However, exposure to CC or HNBT led to reduced secretion of IL-2 and proliferation of Jurkat cells. The exposure of Jurkat T cells to nicotine mimicked the inhibitory effects of exposure to HNBT on IL-2 secretion and T lymphocyte proliferation. The CC released higher concentrations of metals in the exposure chambers. In association, our results show that although exposures to HNBT do not exacerbate inflammatory parameters of AIA or T lymphocyte functions, both products impair lymphoid organ cell function and the proliferation and secretion of IL-2 by T lymphocytes

Nicotine promotes the development of oral leukoplakia via regulating peroxiredoxin 1 and its binding proteins

Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.

Dependência do tabaco e nível de monóxido de carbono em trabalhadores terceirizados / Dependencia del tabaco y nivel de monóxido de carbono enempleados tercerizados / Tobacco dependence and carbon monoxide level in outsourced workers

RESUMO Objetivo: analisar a dependência física do tabaco e o nível de monóxido de carbono no ar exalado (status tabágico) em trabalhadores terceirizados de uma universidade pública. Método: estudo descritivo-analítico, transversal, quantitativo, desenvolvido com 316 trabalhadores terceirizados de uma universidade pública. Os dados foram coletados por meio do instrumento de caracterização dos participantes, do Fagerström Test for Nicotine Dependence e do aparelho monoxímetro. Resultados: dos 316 trabalhadores terceirizados, apenas 41 relataram o uso de tabaco ou derivados e 39% destes possuíam grau de dependência física do tabaco elevado/muito elevado. A maioria (90,2%) deles possuía status tabágico considerados fumantes. As variáveis dependência física do tabaco e nível de monóxido de carbono no ar exalado apresentaram associação estatística (p=0,038). Conclusão: alguns trabalhadores possuíam dependência física ao tabaco; por isso, torna-se importante a criação e adoção de políticas públicas que atendam a este tipo de população, assim como, a presença de um enfermeiro nas empresas, com vistas para a promoção da saúde dos trabalhadores.

RESUMEN Objetivo: analizar la dependencia física del tabaco yel nivel de monóxido de carbono en el aire exhalado (status de tabaquismo) enempleados tercerizados de una universidad pública. Método: estudio descriptivo-analítico, transversal, cuantitativo, desarrollado con 316 empleados tercerizados de una universidad pública. Los datos fueronrecolectados por medio del instrumento de caracterización de los participantes, delFagerström Test forNicotineDependencey delmonitor de monóxido de carbono. Resultados: de los 316 empleados tercerizados, solo 41 relataron el uso de tabaco o derivados yel 39% de estos poseía grado de dependencia física del tabaco elevado/muy elevado. La mayor partede ellos (90,2%) poseía statusde tabaquismo considerados fumadores. Las variables dependencia física del tabaco y nivel de monóxido de carbono en el aire exhalado presentaron asociación estadística (p=0,038). Conclusión: algunos empleados poseían dependencia física al tabaco; por ello, es importante la creacióny adopción de políticas públicas que respondan a este tipo de población, así como la presencia de un enfermero en las empresas, a fin de promover la salud de los empleados.

ABSTRACT Objective: to analyze the physical dependence to tobacco and carbon monoxide levels in the exhaled air (smoking status) in outsourced workers at a public university. Method: descriptive-analytical, cross-sectional, quantitative study developed with 316 outsourced workers from a public university. Data were collected using an instrument for characterization of the participants, the Fagerström Test for Nicotine Dependence, and measurements with a monoximeter. Results: of the 316 outsourced workers, only 41 reported the use of tobacco or tobacco products and 39% of them had a high/very high degree of physical dependence to tobacco. The majority (90.2%) had smoking status considered of smokers. The variables physical dependence to tobacco and level of carbon monoxide in exhaled air showed a statistical association (p= 0.038). Conclusion: some workers had physical dependence to tobacco; therefore, the creation and adoption of public policies aimed at this type of population and the presence of nurses in companies are important to promote the health of workers.

Advances in Immunotherapy for Drug Addiction / 中国医学科学院学报

Drug addiction is a major worldwide medical and social problem.Cocaine,nicotine,methamphetamine,heroin and other psychoactive substances,with small molecular weight,can easily cross the blood-brain barrier and eventually lead to addiction and other serious neuropsychological damage.There is no effective cure for addiction currently.The drug-antibody complex formed on the basis of active or passive immunotherapy could not cross the blood-brain barrier,which reduces the concentration of the free active drug and prevents its distribution in the brain,thereby weakening the drug addiction-related reward effects.It provides a promising way for the treatment of drug addiction.This article reviews the progress of immunotherapy against psychoactive substances such as cocaine,nicotine,methamphetamine and heroin in the past 50 years from the aspects of active immunity,passive immunity,drug metabolism-related enzymes,adjuvants and so on.The goal is to provide some ideas for the development of agents for the treatment of psychoactive substance addiction.

N-acetylcysteine as an adjunctive treatment for smoking cessation: a randomized clinical trial

Objective: This randomized controlled trial examined the efficacy and safety of N-acetylcysteine as an adjunctive treatment for smoking cessation. Methods: Heavy smokers were recruited from smoking cessation treatment for this 12- week randomized controlled trial. Eligible tobacco use disorder outpatients (n=34) were randomized to N-acetylcysteine or placebo plus first-line treatment. Abstinence was verified by exhaled carbon monoxide (COexh). The assessment scales included the Fagerström Test for Nicotine Dependence, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Minnesota Nicotine Withdrawal Scale, and the Medication Adherence Rating Scale. We also assessed anthropometrics, blood pressure, lipid profile, and soluble tumor necrosis factor receptor (sTNF-R) levels 1 and 2. Results: First-line treatment for smoking cessation plus adjunctive N-acetylcysteine or placebo significantly reduced COexh (p < 0.01). In the N-acetylcysteine group, no significant changes were found in nicotine withdrawal symptoms, depressive and anxiety symptoms, anthropometric measures, blood pressure, or glucose compared to placebo. However, there was a significant reduction in sTNF-R2 levels between baseline and week 12 in the N-acetylcysteine group. Conclusions: These findings highlight the need to associate N-acetylcysteine with first-line treatment for smoking cessation, since combined treatment may affect inflammation and metabolism components. Clinical trial registration: NCT02420418

In-vitro model of scardovia wiggsiae biofilm formation and effect of nicotine

Abstract Recently, Scardovia wiggsiae has been reported to be strongly associated with caries formation. This study aimed to establish an in vitro model of S. wiggsiae biofilm and to investigate the effect of nicotine on S. wiggsiae colony-forming units (CFUs) growth. S. wiggsiae biofilm was grown overnight using brain-heart infusion (BHI) broth supplemented with 5 g of yeast extract/L (BHI-YE). The overnight culture was used as an inoculum to grow S. wiggsiae biofilm on standardized enamel and dentin samples. Samples were incubated with different nicotine concentrations (0, 0.5, 1, 2, 4, 8, 16 and 32 mg/mL) for 3 days. The dissociated biofilms were diluted, spiral plated on blood agar plates, and incubated for 24 h. CFUs/mL were quantified using an automated colony counter. A two-way ANOVA was used to compare the effect of different nicotine concentrations on S. wiggsiae CFUs. This study demonstrated that S. wiggsiae biofilm could be initiated and formed in vitro. Increased CFUs was observed through 0.5-4 mg/mL and 0.5-8 mg/mL of nicotine using enamel and dentin substrates, respectively. 16 and 32 mg/mL of nicotine were determined as the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), respectively. S. wiggsiae formed greater biofilm on enamel than dentin specimens in response to the nicotine stimulus. This study demonstrated the negative effect of smoking on increasing S. wiggsiae biofilm. Establishing S. wiggsiae biofilm in vitro may allow researchers in the future to have a better understanding of caries pathogenesis and bacterial interaction.

Resumo Recentemente, foi relatado que Scardovia wiggsiae está fortemente associado à formação de cáries. Este estudo teve como objetivo estabelecer um modelo in vitro de biofilme de S. wiggsiae e investigar o efeito da nicotina no crescimento de unidades formadoras de colônias (UFC) de S. wiggsiae. O biofilme de S. wiggsiae foi cultivado durante a noite usando caldo de infusão de cérebro-coração (BHI) suplementado com 5 g de extrato de levedura / L (BHI-YE). A cultura noturna foi usada como um inóculo para cultivar biofilme de S. wiggsiae em amostras padronizadas de esmalte e dentina. As amostras foram incubadas com diferentes concentrações de nicotina (0, 0,5, 1, 2, 4, 8, 16 e 32 mg/mL) por 3 dias. Os biofilmes dissociados foram diluídos, semeados em espiral em placas de ágar sangue e incubados por 24 h. UFC/mL foram quantificados usando um contador de colônias automatizado. Uma ANOVA de duas vias foi usada para comparar o efeito de diferentes concentrações de nicotina em UFCs de S. wiggsiae. Este estudo demonstrou que o biofilme de S. wiggsiae pode ser iniciado e formado in vitro. UFCs aumentadas foram observadas com 0,5-4 mg/mL e 0,5-8 mg/mL de nicotina usando substratos de esmalte e dentina, respectivamente. A concentração inibitória mínima (CIM) e a concentração bactericida mínima (CBM) de nicotina foram determinadas, respectivamente, como 16 e 32 mg/mL. S. wiggsiae formou maior biofilme no esmalte do que espécimes de dentina em resposta ao estímulo de nicotina. Este estudo demonstrou o efeito negativo do tabagismo no aumento do biofilme de S. wiggsiae. O estabelecimento do biofilme de S. wiggsiae in vitro pode permitir que os pesquisadores no futuro tenham uma melhor compreensão da patogênese da cárie e da interação bacteriana.

Efecto del Cigarrillo Electrónico sobre los Espermatozoides Humanos: Aproximación in vitro / Effect of Electronic Cigarette on Human Sperm: in vitro Approximation

Introducción Los cigarrillos electrónicos (E-Cig) aparecieron en el mercado hace 15 años como una alternativa para combatir el consumo de tabaco, un problema de salud pública, sin embargo, su efecto sobre la salud reproductiva no ha sido completamente evaluado. El objetivo del presente estudio, fue evaluar los efectos de los E-Cig sobre los espermatozoides humanos in vitro. Métodos Un dispositivo para incubar en contacto directo a los espermatozoides con el vapor a partir de dos esencias diferentes (TNT y Sugar Drizzle), el humo del cigarrillo o aire como control negativo fue construido. Adicionalmente, usando el mismo dispositivo, se elaboró el extracto a partir del aire, de las dos esencias con el E-Cig y con el cigarrillo Piel Roja sin filtro en medio para incubar en contacto indirecto con los espermatozoides. Resultados Se observó disminución de la movilidad con el E-Cig en más del 38% en el tiempo y una disminución de la viabilidad en más del 18% que se mantenían con el tiempo mientras que con el cigarrillo convencional afectaba la movilidad y la viabilidad en casi el 100%. Finalmente se encontró que se afecta más la movilidad de los espermatozoides con la esencia de Sugar Drizzle que contaba con menos concentración de nicotina que con la esencia de TNT. Conclusiones En conclusión, tanto el cigarrillo convencional como el E-Cig afectan los parámetros seminales (movilidad y viabilidad), y se postula que el uso del E-Cig, aunque es menos citotóxico y afecta menos que el cigarrillo convencional, también puede generar a largo plazo problemas de infertilidad.

Introduction Electronic cigarettes (E-Cig) appeared in the market 15 years ago as an alternative to combat tobacco use, a public health problem, however, its effect on reproductive health has not been fully evaluated. The objective of the present study was to evaluate the effects of E-Cig on human sperm in vitro. Methods A device to incubate sperm in direct contact with steam from two different scents (TNT and Sugar Drizzle), cigarette smoke or air as a negative control was built. Additionally, using the same device, extracts were elaborated from the air, from the two essences with the E-Cig and with the Red Skin cigarette without a filter in the medium to incubate in indirect contact with sperm cells. Results Decreased motility with E-Cig was observed in more than 38% over time and a decrease in viability in more than 18% that was maintained over time while with the conventional cigarette affected motility and viability in almost 100%. Finally, we found that sperm motility of the sperm is more affected with the essence of Sugar Drizzle that had less nicotine concentration than with TNT essence. Conclusions In conclusion, both the conventional cigarette and the E-Cig affect the seminal parameters (motility and viability) and it is postulated that the use of the E-Cig, although it is less cytotoxic and affects less than the conventional cigarette can also generate long-term infertility problems