RESUMO
INTRODUCTION: Pregnant women exposed chronically to opioids smoked more cigarettes per day (CPD) and had a higher nicotine metabolite ratio (NMR), 3-hydroxycotinine/cotinine, a biomarker of nicotine metabolism and clearance, than those not receiving opioids. We examined CPD and NMR in a group of pregnant smokers, a quarter of whom were receiving opioid agonist therapy (OAT). AIMS AND METHODS: Pregnant smokers recruited to participate in a placebo-controlled trial of bupropion for smoking cessation provided a blood sample for measurement of NMR. RESULTS: Half (52.4%) of the 124 women with NMR data were African American. OAT-treated women (n = 34, 27.4%; 27 receiving methadone and 7 buprenorphine) were more likely to be white (79% vs. 30%, p < .001) and to have a lower mean PHQ-9 total score (2.91 [SD = 2.83] vs. 4.83 [SD = 3.82], p = .007). OAT-treated women reported smoking more CPD (9.50 [SD = 5.26] vs. 7.20 [SD = 3.65], p = .005) and had higher NMR (0.78 [SD = 0.36] vs. 0.56 [SD = 0.25], p = .001) than the non-OAT-treated group. In a linear regression analysis adjusting for race, depression severity, and CPD, NMR was greater in the OAT group (p = .025), among whom the daily methadone-equivalent dosage correlated with NMR (Spearman's ρ = 0.49, p = .003). CONCLUSIONS: Consistent with the findings of Oncken et al. (2019), we found that OAT smokers smoked more and had higher NMR than non-OAT smokers. As higher NMR is associated with a reduced likelihood of smoking cessation, the effects on NMR of both pregnancy and OAT could contribute to a lower smoking cessation rate in pregnant smokers receiving chronic opioid therapy. IMPLICATIONS: We replicated the finding that the NMR is significantly greater among pregnant smokers receiving OAT than those not receiving this treatment for opioid use disorder. Furthermore, we found that the dosage of the OAT was significantly associated with the NMR level. These findings may contribute to a poorer response to smoking cessation treatment in pregnant women treated with OAT, particularly those receiving high-dose therapy, and raise the question of whether novel approaches are needed to treat smoking in this subgroup of pregnant smokers.
Assuntos
Cotinina , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Fumar/tratamento farmacológico , Analgésicos Opioides/agonistas , Bupropiona/uso terapêutico , Cotinina/análogos & derivados , Cotinina/sangue , Cotinina/metabolismo , Feminino , Humanos , Metadona/uso terapêutico , Nicotina/sangue , Nicotina/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Gravidez , Complicações na Gravidez/metabolismo , Abandono do Hábito de FumarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera (Less.) DC is a perennial subshrub, popularly known as "carqueja," that belongs to the Asteraceae family. Ethnobotanical studies indicate that this species is used for the treatment of diabetes and digestive and liver diseases. However, studies that sought to validate its popular use were conducted using ethanolic extracts of the plant, which does not reflect the ethnomedicinal use of this species in humans. AIM OF THE STUDY: Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the liver that can progress to cirrhosis and hepatocellular carcinoma. Because of the severity of this disease, less toxic and more effective therapeutic agents need to be developed. B. trimera may be a promising therapeutic alternative, but its activity against multiple risk factors for liver disease (e.g., smoking, dyslipidemia, and diabetes mellitus) has not been studied. The present study investigated the effects of an ethnomedicinal form of a B. trimera preparation in a rat model of NAFLD that is associated with multiple risk factors. MATERIAL AND METHODS: Phytochemical analysis of the ethanolic soluble fraction of B. trimera extract was performed using ultra-performance liquid chromatography coupled to high-resolution mass spectrometry. Streptozotocin was used to induce diabetes in male Wistar rats. The rats received a 0.5% cholesterol-enriched diet and were exposed to cigarette smoke (9 cigarettes/day, 5 days/week, for 4 weeks). In the last 2 weeks, the animals were orally treated with vehicle (negative control group), B. trimera extract (30, 100, and 300 mg/kg), or insulin + simvastatin. One group of rats that was not exposed to these risk factors was also evaluated. Blood was collected for glucose, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) analysis. The liver and feces were collected for lipid quantification. The liver was additionally processed for histopathological analysis. RESULTS: The model successfully induced NAFLD and increased levels of glucose, AST, and ALT in the negative control group. Treatment with the B. trimera extract (30 and 100 mg/kg) and insulin + simvastatin decreased hepatic and fecal lipids. In contrast to insulin + simvastatin treatment, all three doses of B. trimera effectively reduced AST and ALT levels. CONCLUSION: B. trimera may be promising as a hepatoprotective agent against hepatic lesions that are caused by multiple risk factors.
Assuntos
Baccharis , Diabetes Mellitus Experimental/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Fumar/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Colesterol/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Dislipidemias/complicações , Dislipidemias/metabolismo , Dislipidemias/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos Wistar , Fatores de Risco , Fumar/metabolismo , Fumar/patologia , Triglicerídeos/metabolismoRESUMO
BACKGROUND: The identification of variants in genes involved in nicotine metabolism may have implications for the pharmacological therapy of smoking. In the scenario of precision medicine, the aim of this study was to evaluate a possible association of cytochrome P450 2A6 and 2B6 polymorphisms with varenicline pharmacotherapy. METHODS: The present study included 167 patients treated with varenicline in monotherapy who were from a cohort study of 1049 patients (treated with smoking cessation drugs: nicotine replacement therapy, bupropion, varenicline, or combinations of same). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. The CYP2A6 rs1801272 and rs28399433 and CYP2B6 rs8109525 polymorphisms were genotyped by real-time PCR using the TaqMan® platform. RESULTS: Patients with AG or GG genotypes for CYP2B6 rs8109525 had a higher success rate of smoking cessation with varenicline (51.2%) compared with carriers of the AA genotypes (33.3%, P = 0.03, n = 167). The AG or GG genotypes were also associated with a higher odds ratio of success, even in a multivariate analysis adjusting for potential confounders (OR = 2.01; 95%CI = 1.01 to 4.00; P = 0.047). CONCLUSION: CYP2B6 rs8109525 was associated with a higher success rate of smoking cessation with varenicline treatment. This finding may be useful in pharmacogenomic strategies for smoking cessation therapy.
Assuntos
Citocromo P-450 CYP2B6/genética , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Abandono do Hábito de Fumar/estatística & dados numéricos , Fumar/tratamento farmacológico , Vareniclina/uso terapêutico , Adulto , Citocromo P-450 CYP2A6/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fumar/genética , Resultado do TratamentoAssuntos
Humanos , Terapia Comportamental , Abandono do Hábito de Fumar/métodos , Aconselhamento/métodos , Prevenção do Hábito de Fumar , Psicoterapia de Grupo , Grupos de Autoajuda , Literatura de Revisão como Assunto , Fumar/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Metanálise como Assunto , Abandono do Hábito de Fumar/estatística & dados numéricos , Dispositivos para o Abandono do Uso de Tabaco , Revisões Sistemáticas como AssuntoRESUMO
Chronic obstructive pulmonary disease (COPD) is an incurable and progressive disease. Emphysema is the principal manifestation of COPD, and the main cause of this condition is cigarette smoke (CS). Natural products have shown antioxidant and anti-inflammatory properties that can prevent acute lung inflammation and emphysema, but there are few reports in the literature regarding therapeutic approaches to emphysema. We hypothesized that supplementation with natural extracts would repair lung damage in emphysema caused by CS exposure. Mice were exposed to 60days of CS and then treated or not with three different natural extracts (mate tea, grape and propolis) orally for additional 60days. Histological analysis revealed significant improvements in lung histoarchitecture, with recovery of alveolar spaces in all groups treated with natural extracts. Propolis was also able to recovery alveolar septa and elastic fibers. Propolis also increased MMP-2 and decreased MMP-12 expression, favoring the process of tissue repair. Additionally, propolis recruited leukocytes, including macrophages, without ROS release. These findings led us to investigate the profile of these macrophages, and we showed that propolis could promote macrophage alternative activation, thus increasing the number of arginase-positive cells and IL-10 levels and favoring an anti-inflammatory microenvironment. We further investigated the participation of Nrf2 in lung repair, but no Nrf2 translocation to the nucleus was observed in lung cells. Proteins and enzymes related to Nrf2 were not altered, other than NQO1, which seemed to be activated by propolis in a Nrf2-independent manner. Finally, propolis downregulated IGF1 expression. In conclusion, propolis promoted lung repair in a mouse emphysema model via macrophage polarization from M1 to M2 in parallel to the downregulation of IGF1 expression in a Nrf2-independent manner.
Assuntos
Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Própole/farmacologia , Enfisema Pulmonar/tratamento farmacológico , Fumar/tratamento farmacológico , Animais , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patologia , Fumar/metabolismoRESUMO
Resumen La hospitalización es una oportunidad valiosa para el abandono del tabaquismo, desaprovechada en Chile. La necesidad de hospitalizarse está determinada por enfermedades muchas veces causadas por el consumo de tabaco, este escenario permite al paciente valorar no solo las consecuencias de esta adicción, si no también, la importancia de suspender el consumo. Es esperable que durante la hospitalización aparezca el síndrome de abstinencia de nicotina, cuyo reconocimiento y manejo es fundamental para evitar complicaciones habituales: ansiedad o delirium. Por todo lo anterior, resulta necesario el adecuado enfrentamiento del tabaquismo en el paciente hospitalizado, lo que es reconocido por organismos acreditadores internacionales como Joint Commission. Un metanálisis Cochrane 2012 concluyó que los dos pilares fundamentales de las intervenciones efectivas fueron el carácter multimodal (consejería y tratamiento farmacológico), y el seguimiento ambulatorio por más de un mes posterior al alta. Los elementos centrales de una consejería breve pueden resumirse en el ABC, siendo A: averiguar sobre el consumo de tabaco; B: dar un consejo breve indicando la importancia de dejar de fumar, y C: Ofrecer apoyo para la cesación a los pacientes que se muestren motivados. Si bien las intervenciones mencionadas involucran contar con recursos para apoyo farmacológico, no pareciera haber excusas para seguir sin implementar en los hospitales chilenos intervenciones sencillas como documentar el estado tabáquico de cada paciente y ofrecer consejería breve.
Hospitalization is a valuable opportunity for smoking cessation. In Chile this opportunity is wasted. The need to hospitalize is determined by diseases often caused by smoking, this scenario allows the patient to assess not only the consequences of this addiction, but also the importance of stopping tobacco consumption. During hospitalization, the nicotine withdrawal syndrome appears, whose recognition and management is essential to avoid habitual complications: anxiety or delirium. For all of the above mentioned reasons, it is necessary the adequate confrontation of smoking in the hospitalized patient, which is recognized by international accreditation bodies as Joint Commission. A Cochrane metaanalysis 2012 concluded that the two pillars of effective interventions were the multimodal character (counseling and pharmacological treatment), and ambulatory follow-up for more than one month after discharge. The central elements of a brief counseling can be summarized in ABC, where A: ask about smoking; B: give brief advice stating the importance of quitting, and C: provide support for cessation for motivated patients. Although the above-mentioned interventions involve resources for pharmacological support, there seems to be no excuse for implementing simple interventions in Chilean hospitals, such as documenting the smoking status of each patient and offering brief counseling.
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Síndrome de Abstinência a Substâncias , Fumar/tratamento farmacológico , Abandono do Hábito de Fumar/estatística & dados numéricos , Agonistas Nicotínicos/uso terapêutico , Pacientes Internados , Fumar/epidemiologia , Chile/epidemiologia , Prevalência , Resultado do Tratamento , Abandono do Hábito de Fumar/métodos , Hospitalização/estatística & dados numéricosRESUMO
BACKGROUND: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. AIM: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. PATIENTS AND METHODS: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. RESULTS: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). CONCLUSIONS: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.
Assuntos
Agonistas Nicotínicos/uso terapêutico , Avaliação de Programas e Projetos de Saúde , Abandono do Hábito de Fumar/métodos , Fumar/tratamento farmacológico , Vareniclina/uso terapêutico , Adulto , Idade de Início , Idoso , Escolaridade , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/normas , Fumar/efeitos adversos , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Resultado do TratamentoRESUMO
Background: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. Aim: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. Patients and Methods: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. Results: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). Conclusions: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Avaliação de Programas e Projetos de Saúde , Fumar/tratamento farmacológico , Abandono do Hábito de Fumar/métodos , Agonistas Nicotínicos/uso terapêutico , Vareniclina/uso terapêutico , Fumar/efeitos adversos , Fumar/psicologia , Métodos Epidemiológicos , Resultado do Tratamento , Abandono do Hábito de Fumar/psicologia , Idade de Início , Escolaridade , Programas Nacionais de Saúde/normasRESUMO
Our aim was to investigate the effects of four different statins on acute lung inflammation induced by cigarette smoke (CS). C57BL/6 male mice were divided into a control group (sham-smoked) and mice exposed to CS from 12 cigarettes/day for 5 days. Mice exposed to CS were grouped and treated with vehicle (i.p.), atorvastatin (10 mg/kg), pravastatin (10 mg/kg), rosuvastatin (5 mg/kg), or simvastatin (20 mg/kg). Treatment with statins differentially improved the pulmonary response when compared to the CS group. Atorvastatin and pravastatin demonstrated slightly effects on inflammation and oxidative stress. Rosuvastatin demonstrated the best anti-inflammatory effect, whereas simvastatin demonstrated the best antioxidant response.