Ovarian hormones do not mediate protection against pulmonary hypertension and right ventricular remodeling in female mice exposed to chronic, inhaled nicotine.

Electronic cigarette use has increased globally prompting calls for improved understanding of nicotine's cardiovascular health effects. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension and right ventricular (RV) remodeling in male mice, but not female mice, suggesting sex differences in nicotine-related pathology. Clinically, biological females develop pulmonary hypertension more often but have less severe disease than biological males, likely because of the cardiopulmonary protective effects of estrogen. Nicotine is also metabolized more rapidly in biological females because of differences in cytochrome-P450 activity, which are thought to be mediated by female sex hormones. These findings led us to hypothesize that female mice are protected against nicotine-induced pulmonary hypertension by an ovarian hormone-dependent mechanism. In this study, intact and ovariectomized (OVX) female mice were exposed to chronic, inhaled nicotine or room air for 12 h/day for 10-12 wk. We report no differences in serum cotinine levels between intact and OVX mice. In addition, we found no structural (RV or left ventricular dimensions and Fulton index) or functional (RV systolic pressure, pulmonary vascular resistance, cardiac output, ejection fraction, and fractional shortening) evidence of cardiopulmonary dysfunction in intact or OVX mice. We conclude that ovarian hormones do not mediate cardiopulmonary protection against nicotine-induced pulmonary hypertension. Due to profound sex differences in clinical pulmonary hypertension pathogenesis and nicotine metabolism, further studies are necessary to elucidate mechanisms underlying protection from nicotine-induced pathology in female mice.NEW & NOTEWORTHY The emergence of electronic cigarettes poses a threat to cardiovascular and pulmonary health, but the direct contribution of nicotine to these disease processes is largely unknown. Our laboratory has previously shown that chronic, inhaled nicotine induces pulmonary hypertension and right ventricular remodeling in male mice, but not female mice. This study using a bilateral ovariectomy model suggests that the cardiopulmonary protection observed in nicotine-exposed female mice may be independent of ovarian hormones.

Socio-environmental risks associated with the green tobacco sickness in farmers: a case-control study / Riesgos socioambientales asociados a la enfermedad del tabaco verde en agricultores: un estudio caso-control / Riscos socioambientais associados à doença da folha verde do tabaco em agricultores: um estudo caso-controle

ABSTRACT Objective: to determine the presence of socio-environmental risk factors for the development of Green Tobacco Sickness in workers who grow Burley tobacco. Method: matched case-control study. The data collection took place in two moments: from December 2016 to January 2017 and December 2017, when the Burley tobacco was collected, through a household survey with interview application and urine collection for urinary cotinine. Results: the socio-environmental risk factors that remained associated with the disease were: bundling tobacco (p=0.047) and wearing socks (p=0.011); with protective effect were found sticking tobacco seeding of the day (p=0.006) and number of tobacco harvested per day (p=0.021). Conclusion: the steps in the Burley tobacco work process increase the exposure and risk of developing the disease. By identifying these factors, it is possible to address interdisciplinary control and prevention measures.

RESUMEN Objetivo: determinar la presencia de factores de riesgo socioambientales para el desarrollo de la Enfermedad del Tabaco Verde en trabajadores que cultivan el tabaco Burley. Método: estudio del tipo caso-control pareado. La recolección de datos ocurrió en dos momentos: de diciembre de 2016 a enero de 2017 y diciembre de 2017, período en que ocurrió la recolección del tabaco Burley, por medio de encuesta domiciliaria con aplicación de entrevista y recolección de orina para el examen de cotinina urinaria. Resultados: los factores de riesgo socioambientales que permanecieron asociados a la enfermedad fueron aferrar tabaco (p=0,047) y usar medias (p=0,011); con efecto protector fueron encontrados espetar los pies de tabaco del día (p=0,006) y el número de pies de tabaco cosechados por día (p=0,021). Conclusión: las etapas del proceso de trabajo con tabaco Burley aumentan la exposición y el riesgo de desarrollar la enfermedad. Al identificar estos factores, es posible dirigir, de forma interdisciplinaria, medidas de control y prevención.

RESUMO Objetivo: determinar a presença de fatores de riscos socioambientais para o desenvolvimento da Doença da Folha Verde do Tabaco em trabalhadores que cultivam o tabaco Burley. Método: estudo do tipo caso-controle pareado. A coleta de dados ocorreu em dois momentos: de dezembro de 2016 a janeiro de 2017 e dezembro de 2017, período em que ocorreu a colheita do tabaco Burley, por meio de inquérito domiciliar com aplicação de entrevista e coleta de urina para exame de cotinina urinária. Resultados: os fatores de riscos socioambientais que permaneceram associados à doença foram enfeixar tabaco (p=0,047) e usar meias (p=0,011); com efeito protetor foram encontrados espetar pés de tabaco do dia (p=0,006) e número de pés de tabaco colhido por dia (p=0,021). Conclusão: as etapas do processo de trabalho com tabaco Burley aumentam a exposição e o risco de desenvolver a doença. Ao identificar esses fatores, é possível direcionar, de forma interdisciplinar, medidas de controle e prevenção.

Socio-environmental risks associated with the green tobacco sickness in farmers: a case-control study.

OBJECTIVE: to determine the presence of socio-environmental risk factors for the development of Green Tobacco Sickness in workers who grow Burley tobacco. METHOD: matched case-control study. The data collection took place in two moments: from December 2016 to January 2017 and December 2017, when the Burley tobacco was collected, through a household survey with interview application and urine collection for urinary cotinine. RESULTS: the socio-environmental risk factors that remained associated with the disease were: bundling tobacco (p=0.047) and wearing socks (p=0.011); with protective effect were found sticking tobacco seeding of the day (p=0.006) and number of tobacco harvested per day (p=0.021). CONCLUSION: the steps in the Burley tobacco work process increase the exposure and risk of developing the disease. By identifying these factors, it is possible to address interdisciplinary control and prevention measures.

Adrenal ßarrestin1 targeting for tobacco-associated cardiac dysfunction treatment: Aldosterone production as the mechanistic link.

Tobacco kills 6 million people annually and its global health costs are continuously rising. The main addictive component of every tobacco product is nicotine. Among the mechanisms by which nicotine, and its major metabolite, cotinine, contribute to heart disease is the renin-angiotensin-aldosterone system (RAAS) activation. This increases aldosterone production from the adrenals and circulating aldosterone levels. Aldosterone is a mineralocorticoid hormone with various direct harmful effects on the myocardium, including increased reactive oxygen species (ROS) generation, which contributes significantly to cardiac mitochondrial dysfunction and cardiac aging. Aldosterone is produced in the adrenocortical zona glomerulosa (AZG) cells in response to angiotensin II (AngII), activating its type 1 receptor (AT1R). The AT1R is a G protein-coupled receptor (GPCR) that leads to aldosterone biosynthesis and secretion, via signaling from both Gq/11 proteins and the GPCR adapter protein ßarrestin1, in AZG cells. Adrenal ßarrestin1 is essential for AngII-dependent adrenal aldosterone production, which aggravates heart disease. Since adrenal ßarrestin1 is essential for raising circulating aldosterone in the body and tobacco compounds are also known to elevate aldosterone levels in smokers, accelerating heart disease progression, our central hypothesis is that nicotine and cotinine increase aldosterone levels to induce cardiac injury by stimulating adrenal ßarrestin1. In the present review, we provide an overview of the current literature of the physiology and pharmacology of adrenal aldosterone production regulation, of the effects of tobacco on this process and, finally, of the effects of tobacco and aldosterone on cardiac structure and function, with a particular focus on cardiac mitochondrial function. We conclude our literature account with a brief experimental outline, as well as with some therapeutic perspectives of our pharmacological hypothesis, that is that adrenal ßarrestin1 is a novel molecular target for preventing tobacco-induced hyperaldosteronism, thereby also ameliorating tobacco-related heart disease development.

Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5.

Tobacco and alcohol are often co-abused. Nicotine can enhance alcoholic fatty liver, and CYP2A6 (CYP2A5 in mice), a major metabolism enzyme for nicotine, can be induced by alcohol. CYP2A5 knockout (cyp2a5-/-) mice and their littermates (cyp2a5+/+) were used to test whether CYP2A5 has an effect on nicotine-enhanced alcoholic fatty liver. The results showed that alcoholic fatty liver was enhanced by nicotine in cyp2a5+/+ mice but not in the cyp2a5-/- mice. Combination of ethanol and nicotine increased serum triglyceride in cyp2a5+/+ mice but not in the cyp2a5-/- mice. Cotinine, a major metabolite of nicotine, also enhanced alcoholic fatty liver, which was also observed in cyp2a5+/+ mice but not in the cyp2a5-/- mice. Nitrotyrosine and malondialdehyde (MDA), markers of oxidative/nitrosative stress, were induced by alcohol and were further increased by nicotine and cotinine in cyp2a5+/+ mice but not in the cyp2a5-/- mice. Reactive oxygen species (ROS) production during microsomal metabolism of nicotine and cotinine was increased in microsomes from cyp2a5+/+ mice but not in microsomes from cyp2a5-/- mice. These results suggest that nicotine enhances alcoholic fatty liver in a CYP2A5-dependent manner, which is related to ROS produced during the process of CYP2A5-dependent nicotine metabolism.

Association Between Chronic Exposure to Tobacco Smoke and Accumulation of Toxic Metals in Hair Among Pregnant Women.

Tobacco smoke contains various toxic heavy metals that individuals are exposed to when they smoke. Despite the presence of heavy metals in tobacco smoke, the relationship between smoking and the accumulation of toxic metals in pregnant women after long-term exposure remains under discussion. We examined the association between long-term exposure to tobacco smoke and the accumulation of toxic metals in the hair of female participants. Our study recruited 252 women from the Shanxi and Hebei provinces of Northern China; these participants were self-reported non-active smokers, and had previously delivered healthy babies without birth defects. Scalp hair was collected and analyzed for nicotine and cotinine and five potentially toxic metals (specifically, silver, chromium, cadmium, mercury, and lead). Our results showed significant positive correlations between cotinine and four metals, including silver (r = 0.369, p < 0.001), cadmium (r = 0.185, p < 0.01), mercury (r = 0.161, p < 0.05), and lead (r = 0.243, p < 0.001). Significant positive correlations were also found between nicotine and three metals-specifically silver (r = 0.331, p < 0.001), cadmium (r = 0.176, p < 0.01), and lead (r = 0.316, p < 0.001). A logistic regression model showed significant associations between cotinine and potentially toxic metals including mercury, silver, and lead (with or without adjusting for potential confounders). We thus conclude that long-term passive smoking could potentially increase the exposure level of toxic metals including lead, silver, and mercury in our study, which are especially harmful for pregnant women and their unborn fetus.

Smoking in Pregnancy and Fetal Growth: The Case for More Intensive Assessment.

INTRODUCTION: Many studies on prenatal tobacco exposure (PTE) effects have relied on single item retrospective measures of PTE. However, it is unclear how these single item measures may relate to more intensive maternal self-reports and to biological markers of maternal use and/or fetal exposure. It is also unclear whether these measures may be more valid predictors of fetal growth (gestational age, birthweight, head circumference, and birth length). METHODS: Data were obtained from 258 women during their pregnancy. PTE was assessed by four methods: a single item question, a calendar-based self-report measure from each trimester of pregnancy, maternal salivary cotinine assays, and nicotine and metabolites in infant meconium. We hypothesized that the more intensive measures and biological assays would account for additional variance in birth outcomes, above and beyond the single item measure. RESULTS: The single item self-report measure was not related to fetal growth. However, the more intensive calendar based self-report measure and the biological assays of PTE (ie, maternal salivary assays and infant meconium) were significant predictors of poor fetal growth, even with the single item measure in the model. CONCLUSIONS: The negative effects of PTE on important child outcomes may be greatly underestimated in the literature as many studies use single item self-report measures to ascertain PTE. Whereas more intensive self-report measures or biological assays may be cost prohibitive in large scale epidemiological studies, using a combination of measures when possible should be considered given their superiority both identifying prenatal smokers and predicting poor fetal growth. IMPLICATIONS: The present work underscores the importance of measurement issues when assessing associations between PTE and fetal growth. Results suggest that we may be greatly underestimating the negative effects of prenatal smoking on fetal growth and other important child outcomes if we rely solely on restricted single item self-report measures of prenatal smoking. Researchers should consider more intensive prospective self-report measures and biological assays as viable and superior alternatives to single item self-report measures.

The effects of passive tobacco smoking on the microcirculation of the abdominal wall in rats.

PURPOSE:: To analysis the effects of passive smoking on the microstructure of tissues of the abdominal wall regarding microcirculation, using histopathological study of the tobacco exposed rats. METHODS:: Twenty four male Wistar rats were divided in Control Group (CG = 8 animals) and Exposition Groups (EG = 16 animals). EG was exposed to cigarette smoke 4x/day for 120 days, while CG was preserved from exposure. Food, water and housing were similar for both groups. After 120 days, urine samples were collected before necropsy to analyze cotinine levels (ng/mL) in urine and blinded histopathological analysis of the abdominal wall performed to count arteries and veins in dermal and muscular fascia layer. RESULTS:: No difference in weight was observed between both groups (P>0.05). Cotinine concentration was significantly higher in EG (P<0.05). In dermal layer, the average of vessels per animal was 8.72 (IC95%: 8.31-9.13) for CG and 11,23 (IC95%: 10.09-12.38) for EG. In muscular fascia layer the average of vessels per animal was 17.97 (IC95%: 15.79-20.15) for CG, whereas the average for EG was of 14,85 (IC95%: 12.71-17.01) (P<0.05). CONCLUSION:: Exposition to passive smoking may cause increase in the number of vessels in dermal layer, with the opposite effects at the muscular fascia layer.

Racial Disparity in the Associations of Cotinine with Insulin Secretion: Data from the National Health and Nutrition Examination Survey, 2007-2012.

BACKGROUND: Although relationships between smoking/high cotinine and type 2 diabetes have consistently been observed, few studies have investigated the relationship between cotinine and underlying pathophysiological defects that characterize diabetes aetiology. This study aimed to test the associations between cotinine and measures of insulin resistance or insulin secretion. METHODS: This analysis included 5,751 non-diabetic adult American from the National Health and Nutrition Examination Survey (NHANES) from 2007-2012. Insulin function was represented with two indexes: insulin resistance index (HOMA-IR) and insulin secretion index (HOMA-B) estimated by homeostasis model assessment. We categorized cotinine levels into quartiles and estimated the odds of HOMA-IR in the 4th quartile and HOMA-B in the 1st quartile among cotinine categories using multiple logistic regression models. RESULTS: Cotinine concentration was not associated with the risk of high HOMA-IR. Association of cotinine with low HOMA-B existed and differed by race/ethnicity (P for interaction<0.05). High cotinine concentration (in the 4th quartile) was associated with an increased risk of low HOMA-B compared with low cotinine concentrations(1st -2nd quartiles) among white (odds ratio[OR], 1.51 [95% confidence interval[CI], 1.16-1.97]) or black participants (OR, 2.98 [95%CI, 1.90-4.69]) but not among Mexican (OR, 1.79 [95%CI, 0.90-3.53]) or other Hispanic(OR, 1.02 [95%CI, 0.56-1.86]) participants. Such associations remained significant even after further adjustment for HOMA-IR. CONCLUSIONS: High cotinine is associated with decreased insulin secretion function only in white and black non-diabetic U.S. adult population. Results evaluating cotinine in ethnically homogeneous populations may not be broadly generalizable to other racial/ethnic groups.

The effects of passive tobacco smoking on the microcirculation of the abdominal wall in rats

ABSTRACT PURPOSE: To analysis the effects of passive smoking on the microstructure of tissues of the abdominal wall regarding microcirculation, using histopathological study of the tobacco exposed rats. METHODS: Twenty four male Wistar rats were divided in Control Group (CG = 8 animals) and Exposition Groups (EG = 16 animals). EG was exposed to cigarette smoke 4x/day for 120 days, while CG was preserved from exposure. Food, water and housing were similar for both groups. After 120 days, urine samples were collected before necropsy to analyze cotinine levels (ng/mL) in urine and blinded histopathological analysis of the abdominal wall performed to count arteries and veins in dermal and muscular fascia layer. RESULTS: No difference in weight was observed between both groups (P>0.05). Cotinine concentration was significantly higher in EG (P<0.05). In dermal layer, the average of vessels per animal was 8.72 (IC95%: 8.31-9.13) for CG and 11,23 (IC95%: 10.09-12.38) for EG. In muscular fascia layer the average of vessels per animal was 17.97 (IC95%: 15.79-20.15) for CG, whereas the average for EG was of 14,85 (IC95%: 12.71-17.01) (P<0.05). CONCLUSION: Exposition to passive smoking may cause increase in the number of vessels in dermal layer, with the opposite effects at the muscular fascia layer.

Cigarette smoking and testosterone in men and women: A systematic review and meta-analysis of observational studies.

Recently Health Canada and the Food and Drug Administration warned about the cardiovascular risk of testosterone, making environmental drivers of testosterone potential prevention targets. Cotinine, a tobacco metabolite, inhibits testosterone breakdown. We assessed the association of smoking with testosterone in a systematic review and meta-analysis, searching PubMed and Web of Science through March 2015 using ("testosterone" or "androgen" or "sex hormone") and ("smoking" or "cigarette"). Two reviewers independently searched, selected, assessed quality and abstracted with differences resolved by consensus or reference to a third reviewer. The initial search yielded 2881 studies; 28 met the selection criteria. In 22 studies of 13,317 men, mean age 18-61years, smokers had higher mean testosterone than non-smokers (1.53nmol/L, 95% confidence interval (CI) 1.11 to 1.96) using a random effects model with inverse variance weighting. In 6 studies of 6089 women, mean age 28-62years, smoking was not clearly associated with testosterone (0.11nmol/L, 95% CI -0.08 to 0.30). Fixed effects models provided similar results, but suggested a positive association in women. Whether products which raise cotinine, such as e-cigarettes or nicotine replacement, also raise testosterone, should be investigated, to inform any regulatory action for e-cigarettes, which emit nicotine into the surrounding air, with relevance for both active and passive smokers.

Cytological evaluation of the nasal mucosa in neonates exposed to tobacco smoke during fetal life.

OBJECTIVES: The objective of this study is to assess the cytological picture of the nasal mucosa of neonates born to mothers who are active smokers, passive smokers and non-smokers. METHODS: A prospective study was conducted in a group of 86 neonates born between 23 and 41 weeks of gestation. The assignation of neonates to one of the three aforementioned groups was based on a questionnaire concerning exposure to tobacco smoke, and on the concentration of cotinine in maternal urine. A cytological examination was performed using exfoliative cytology with a semi-quantitative evaluation of the cells present in the specimens. Hematological summation equipment was used to assess the number of neutrophils, eosinophils, columnar, goblet, basal and squamous cells out of 500 cells counted. The number of specific cells was expressed as a percentage and a cytogram was created. RESULTS: The most common type of cytogram contained neutrophils, columnar cells, and squamous cells. No significant differences were observed between the subgroups. Similarly, there was no correlation between the median of each type of cell and the cotinine concentration in the mothers' urine. CONCLUSION: Active and passive smoking during pregnancy do not influence the cytological picture of the nasal mucosa of neonates.

The effect of nicotine and cotinine on human gingival fibroblasts attachment to root surfaces.

BACKGROUND: Different compounds of smoking (e.g., nicotine and cotinine) are risk factors for various diseases such as oral cancer and periodontal diseases. Some studies reported the negative effects of nicotine on cell proliferation and differentiation. The present in vitro study assessed the effects of nicotine and cotinine (long-acting metabolite of nicotine) on the attachment and viability of human gingival fibroblast (HGF) cells to tooth root surfaces. METHODS: A total of 70 teeth specimens were placed into 48-well culture plates and covered with HGF cell suspension, in complete Dulbecco's modified Eagle's medium culture medium containing 1 nM, 1 µm, 1 mM, and 5 mM of nicotine and cotinine concentrations. Cellular attachment and viability measured using an MTT assay and a scanning electron microscope were used for cell morphological evaluation. RESULTS: After 24 h, low (nanomolar and micromolar) and high concentrations (millimolar) of nicotine and cotinine caused a significant reduction in the initial cell adhesion in comparison with the control group, but no significant difference was observed between the nicotine and the cotinine groups (p<0.05). Dentally attached cells with low concentrations of nicotine and cotinine proliferated 48 h after exposure, the same as the control group. However, dentally attached cells with high concentrations of nicotine and cotinine (especially 5 mM) did not proliferate 24 h after exposure (p<0.05). CONCLUSIONS: Low concentrations of nicotine and cotinine caused a reduction in the initial cell adhesion. However, no significant adverse effects on the proliferation of attached cells were seen in the longer period. High concentrations of nicotine and cotinine have adverse effects on the cell adhesion and proliferation of HGF cells.

Neuroactive effects of cotinine on the hippocampus: behavioral and biochemical parameters.

The present work evaluated the effects of nicotine (NIC), cotinine (COT), mecamylamine (MEC), methyllycaconitine (MLA) and dihydro-beta-eritroidine (DHßE) on memory extinction and the following biochemical parameters of the hippocampus: lipid peroxidation (LPO), antioxidant capacity (AC) and the phosphorylation of Extracellular-Signal-Regulated Kinase (ERK 1/2). Young male rats that were implanted bilaterally with cannulae were submitted to memory extinction tests sessions, and their hippocampi were dissected for biochemical assays. The extinction of fear memory was significantly improved by both nicotine and its metabolite. Cotinine significantly increased LPO, while nicotine significantly decreased it. Antioxidant capacity was increased by all treatments. Our results showed that cotinine, unlike nicotine, may increase oxidative stress in the hippocampus, but this increase depends upon the dose used and happens without causing corresponding impairments in cognitive function. Cotinine also increased the phosphorylation of ERK 1/2 in a similar fashion as nicotine. Considering these results, it is plausible to wonder to what extent nicotine-attributed effects are really due to the actions of this alkaloid and whether they could be due instead to cotinine or to cotinine-nicotine interactions within the brain.

Tobacco-induced neuronal degeneration via cotinine in rats subjected to experimental spinal cord injury.

OBJECTIVES: Cigarette smoke contains over 4000 chemicals including well-characterized toxicants and carcinogens, among which is cotinine. Cotinine is the principal metabolite of nicotine that has adverse affects on the microcirculation via vasoconstriction, hypoxia and the wound-healing cascade. Its impact on spinal cord injury (SCI) has not been investigated yet. The aim of the present study is to investigate the cotinine effect on SCI. METHODS: 48 male Wistar rats were divided into six groups as follows: sham-control, sham-trauma, vehicle-control, vehicle-trauma, cotinine-control, and cotinine-trauma. Initially, a defined concentration of cotinine blood level was maintained by daily intraperitoneal injection of cotinine for 14 days in the cotinine groups. The concentration was similar to the cotinine dose in the blood level of heavy smokers. Only ethyl alcohol was injected in the vehicle groups during the same period. Then, SCI was performed by a Tator clip. The cotinine groups were compared with rats subjected to vehicle and sham groups by immunohistochemical biomarkers such as glial fibrillary acidic protein (GFAP) and 2,3-cyclic nucleotide 3-phosphodiesterase (CNP) expressions. Electron microscopic examination was also performed. RESULTS: GFAP-positive cells were noted to be localized around degenerated astrocytes. Marked vacuolization with perivascular and perineural edema was seen in the cotinin consumption groups. These findings showed the inhibition of regeneration after SCI. Similarly, vacuolization within myelin layers was noted in the cotinine groups, which was detected through reduced CNP expression. CONCLUSION: Cotinine, a main metabolite of nicotine, has harmful effects on SCI via GFAP and CNP expression. The findings of the present study support the hypothesis that tobacco causes neuronal degeneration via cotinine.

Fagerström tolerance questionnaire y heavy smoking index. ¿Cuál de los dos test es suficiente para determinar la dependencia en la clínica diaria? / The Fagerström tolerance questionnaire & the heavy smoking index. Which of them is necessary to assess the dependence in the clinical practice?

Objetivo. Conocer la correlación existente entre el Fagerström Tolerance Questionnaire (FTQ) y el Heavy Smoking Index (HSI) para la valoración de la dependencia de la nicotina en la práctica clínica habitual. Métodos. Estudio prospectivo realizado durante el año 2010 en una consulta hospitalaria y en una de atención primaria. Se incluyeron en el estudio 792 fumadores, 437 (55,18%) hombres y 355 (44,82%) mujeres con una edad media de 45,3 {13} y 38,6 {11,8} años, respectivamente. Para valorar la correlación existente entre ambos test se ha utilizado el coeficiente de correlación de Spearman. Resultados. El consumo medio de cigarrillos/día fue de 25,0 y la concentración media de CO de 19,14 ppm. El valor medio del FTNC fue de 7,12 y del HSI 4,39. Ambos test presentan una alta correlación con un coeficiente de Spearman de 0,82 (p=0,000), que es significativa en los grupos con alta y baja dependencia (p=0,000), pero no en el grupo con dependencia moderada (p=0,176). La correlación en función del género fue alta tanto para hombres (r=0,771) como para mujeres (r=0,881). La correlación por grupos de edad fue alta para los tres grupos etarios estudiados: <25 años (r=0,828), 25-49 años (r=0,813) y >50 años (r=0,796). Conclusiones. Existe una buena correlación global entre el Fagerström Tolerance Questionnaire (FTQ) y el Heavy Smoking Index (HSI), que no se modifica en función de variables como edad o género. Por niveles de dependencia, la correlación es buena en pacientes con dependencia alta o moderada y no significativa en el grupo con dependencia moderada (AU)

Objective. To know what is the correlation between Fagerström Tolerance Questionnaire (FTQ) and the Heavy Smoking Index (HSI) in order to examine nicotine dependence in current clinical practice. Methods. Prospective study made in 2010’s tobacco specific medical clinic and primary care. It includes 792 smokers, 437 (55,18%) men and 355 (44,82%) women, with a mean of years old 45,3 [13] and 38,6 [11,8] respectively. In order to assess the existent correlation between both tests we used Spearman’s Correlation Coefficient. Results. The average daily consumption of cigarettes was 25.5 and the mean concentration of CO was 19.14 ppm. The mean value of FTNC was 7.12 and HSI 4.39. Both tests present a high correlation, with a Spearman coefficient of 0.82 (p=0.000). The correlation is significant in high and low dependency groups (p=0.000), but not in the group with moderate dependency (p=0.176). Gender-wise, the correlation was high for men (r=0.771) and women (p=0.881). Regarding age groups, correlation was high for the three groups analyzed: <25 years (r=0.828), 25-49 years (r=0.813) and >50 years (r=0.796). Conclusions. There is a respectable global correlation between Fagerström Tolerance Questionnaire (FTQ) and the Heavy Smoking Index (HSI). This correlation does not vary in front of variables like age or gender. When considering dependency levels, the correlation is significant among high or low dependency and non-significant within the moderate dependency group (AU)

Relationships of cotinine and self-reported cigarette smoking with hemoglobin A1c in the U.S.: results from the National Health and Nutrition Examination Survey, 1999-2008.

OBJECTIVE: Whether nicotine leads to a persistent increase in blood glucose levels is not clear. Our objective was to assess the relationship between cotinine, a nicotine metabolite, and glycated hemoglobin (HbA(1c)), an index of recent glycemia. RESEARCH DESIGN AND METHODS: We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008. We limited our analysis to 17,287 adults without diabetes. We created three cotinine categories: <0.05 ng/mL, 0.05-2.99 ng/mL, and ≥3 ng/mL. RESULTS: Using self-report, 25% of the sample were current smokers, 24% were former smokers, and 51% were nonsmokers. Smokers had a higher mean HbA(1c) (5.36% ± 0.01 SE) compared with never smokers (5.31% ± 0.01) and former smokers (5.31% ± 0.01). In a similar manner, mean HbA(1c) was higher among participants with cotinine ≥3 ng/mL (5.35% ± 0.01) and participants with cotinine 0.05-2.99 ng/mL (5.34% ± 0.01) compared with participants with cotinine <0.05 ng/mL (5.29% ± 0.01). In multivariable-adjusted analysis, we found that both a cotinine ≥3 ng/mL and self-reported smoking were associated with higher HbA(1c) compared with a cotinine <0.05 ng/mL or not smoking. People with a cotinine level ≥3 ng/mL had a relative 5% increase in HbA(1c) compared with people with a cotinine level <0.05 ng/mL, and smokers had a relative 7% increase in HbA(1c) compared with never smokers. CONCLUSIONS: Our study suggests that cotinine is associated with increased HbA(1c) in a representative sample of the U.S. population without diabetes.

Exposição ocupacional e ambiental a agrotóxicos e nicotina na cultura de fumo do município de Arapiraca, AL / Occupational and Environmental Exposure to Pesticides and Nicotine in Tobacco Culture of the Municipality of Arapiraca / AL

No Brasil, o cultivo do tabaco é associado a graves problemas de saúde entre os agricultores, e que podem evoluir para um quadro de depressão e suicídio. A exposição de trabalhadores rurais a agrotóxicos em culturas de tabaco é, na maioria das vezes, tratada como um evento isolado, desconsiderando-se a exposição concomitante a outras substâncias, como a nicotina, presente nas folhas de tabaco. O presente trabalho tem como objetivo analisar as exposições ocupacionais e ambientais a agrotóxicos e nicotina na cultura de tabaco do município de Arapiraca, AL, com ênfase nos efeitos dessas exposições sobre a atividade da enzima acetilcolinesterase (AChE). A partir do conhecimento do processo de trabalho local, um grupo de 72 fumicultores do município foram avaliados com relação exposição a agrotóxicos organofosforados (OP) e carbamatos e à nicotina nos períodos de cultivo e entre-safra do tabaco. A exposição a agentes anticolinesterásicos foi avaliada através da análise da atividade da AChE eritrocitária, enquanto a exposição à nicotina foi avaliada através dos níveis plasmáticos de cotinina. Um grupo composto por 45 indivíduos foi utilizado como controle na comparação da atividade da AChE. Complementarmente, avaliou-se o efeito in vitro da exposição à nicotina e a OP sobre a atividade da AChE. A análise dos resultados mostrou que, nos testes in vitro, a nicotina somente inibiu a AChE em concentrações iguais ou superiores a 0,5mM. A nicotina não apresentou efeito aditivo nas inibições da AChE por etil paroxon in vitro. (...) Seis indivíduos não fumantes apresentaram valores de cotinina entre 50 e 200 ng/mL, caracterizando uma exposição ocupacional a nicotina. A análise dos resultados in vivo mostrou que os níveis de cotinina plasmático apresentado pelos agricultores não têm correlação com a atividade da AChE. Isto aponta para a possibilidade da não ocorrência de um efeito aditivo da exposição à nicotina e agrotóxicos sobre a atividade da AChE, fator que pode ser utilizado para um diagnóstico diferencial entre a exposição a agrotóxicos e à nicotina entre trabalhadores da cultura fumageira.

Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds.

Environmental exposures in-utero may alter the epigenome, thus impacting chromosomal stability and gene expression. We hypothesized that in utero exposures to maternal smoking and perfluoroalkyl compounds (PFCs) are associated with global DNA hypomethylation in umbilical cord serum. Our objective was to determine if global DNA methylation could be used as a biomarker of in utero exposures to maternal smoking and PFCs. Using an ELISA-based method, global DNA methylation was quantified in umbilical cord serum from 30 newborns with high (> 10 ng/ml, mean 123.8 ng/ml), low (range 1-10 ng/ml, mean 1.6 ng/ml) and very low (< 1 ng/ml, mean 0.06 ng/ml) cord serum cotinine levels. Y chromosome analysis was performed to rule out maternal DNA cross-contamination. Cord serum global DNA methylation showed an inverse dose response to serum cotinine levels (p< 0.001). Global DNA methylation levels in cord blood were the lowest among newborns with smoking mothers (mean=15.04%; 95% CI, 8.4, 21.7) when compared to babies of mothers who were second-hand smokers (21.1%; 95% CI, 16.6, 25.5) and non-smokers (mean=29.2%; 95% CI, 20.1, 38.1). Global DNA methylation was inversely correlated with serum PFOA (r= -0.72, p < 0.01) but not PFOS levels. Serum Y chromosome analyses did not detect maternal DNA cross-contamination. This study supports the use of global DNA methylation status as a biomarker of in utero exposure to cigarette smoke and PFCs.