Approaches, challenges, and experience in assessing free nicotine

Delivery of nicotine in the most desirable form is critical in maintaining people's use of tobacco products. Interpretation of results by tobacco industry scientists, studies that measure free-base nicotine directly in tobacco smoke, and the variability of free-base nicotine in smokeless tobacco products all indicate that the form of nicotine delivered to the tobacco user, in addition to the total amount, is an important factor in whether people continue to use the product following their initial exposure. The physiological impact of nicotine varies with the fraction that is in the free-base form and this leads to continued exposure to other toxic tobacco contents and emissions. In addition to evaluating the total nicotine delivered to the user, measuring the fraction of nicotine in the free-base form is critical in understanding and controlling the influence of nicotine on tobacco use.

Influência do tabagismo passivo associado ao exercício físico realizado por ratas durante prenhez e lactação, sobre o desenvolvimento dos filhotes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Bases neurofisiológicas da dependência do tabaco

A maioria dos estudos pré-clínicos e clínicos aponta a nicotina como o principal agente responsável pelo desenvolvimento da dependência ao tabaco. Muitos trabalhos têm demonstrado que as bases neurais da dependência à nicotina são semelhantes àquelas das outras drogas de abuso. A nicotina induz preferência condicionada por lugar e auto-administração e, portanto, atua como reforçador positivo, esse efeito parece ser mediado pelo sistema dopaminérgico mesolímbico. A nicotina também induz à sensibilização comportamental que é provavelmente resultante de alterações da expressão gênica do núcleo acumbens induzidas pela exposição prolongada a essa substância. A suspensão do uso de nicotina resulta em síndrome de abstinência. As evidências indicam que esses sinais e sintomas sejam mediados por receptores colinérgicos nicotínicos centrais e periféricos. Outros neurotransmissores, como por exemplo a serotonina e os peptídeos opióides, também podem estar envolvidos na mediação da dependência e síndrome de abstinência à nicotina. A revisão da literatura mostra a complexidade dos efeitos da nicotina no organismo. A integração entre as abordagens comportamental, neuroquímica e molecular possibilitará a compreensão dos mecanismos neurais da dependência ao tabaco e fornecerá as bases para o desenvolvimento racional de agentes terapêuticos que possam ser utilizados para o tratamento da dependência e síndrome de abstinência ao tabaco.

Genotoxicity of cigarette smoking in maternal and newborn lymphocytes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Remodelação cardíaca induzida pelo tabagismo (tabaquismo)

Previous studies accomplished by our group suggest that tobacco smoke exposure results in cardiac remodeling, with progressive ventricular dysfunction. However, the mechanisms involved in this process are not known. Therefore, our laboratory has been trying to identify the potentials responsible mechanisms for cardiac remodeling induced by tobacco. The blood pressure increase, the renin-angiotensin system and the oxidative stress can modulate this process. On the other hand, the activation of MMP-2 or MMP-9, as well as lipid peroxidation, don't seem to participate of the morphologic and functional alterations induced by tobacco smoke exposure.

Efectos de la administración de betabloqueante en la remodelación ventricular inducida por el tabaquismo en ratas

Background: The role of the adrenergic system on ventricular remodeling induced by cigarette smoking is unknown. Objective: To investigate the influence of propranolol on ventricular remodeling induced by exposure to tobacco smoke. Methods: Rats were divided into three groups: 1) C, n=10 - control group; 2) F, n=10 - animals exposed to tobacco smoke; 3) BB, n=10 - animals receiving propranolol and exposed to tobacco smoke (40 mg/kg/day). After 2 months, the animals underwent echocardiographic and morphometric analyses. One-way ANOVA (mean ± standard deviation) or the Kruskal-Wallis test (median and interquartile interval) was used. Results: Group BB showed a lower heart rate than group F (C = 358 ± 74 bpm, F = 374 ± 53 bpm, BB = 297± 30; P = 0.02). Group F showed greater end-diastolic diameters (C = 18.6 ± 3.4 mm/kg, F = 22.8 ± 1.8 mm/kg, BB = 21.7 ± 1.8 mm/kg; P = 0.003) and left ventricular (LV) end-systolic diameters (C = 8.6 ± 2.1 mm/kg, F = 11.3 ± 1.3 mm/kg, BB = 9.9 ± 1.2 mm/kg; P = 0.004), adjusted for body weight (BW) and a tendency towards a lower ejection fraction (C = 0.90 ± 0.03, F = 0.87 ± 0.03, BB =0.90 ± 0.02; P = 0.07) than group C. Group BB showed a tendency towards a lower LV/BW ratio than group F (C = 1.94 (1.87 - 1.97), F = 2.03 (1.9-2.1) mg/g, BB = 1.89 (1.86-1.94); P = 0.09). Conclusion: Administration of propranolol attenuated some of the variables of ventricular remodeling induced by the exposure to tobacco smoke in rats.

Cardiovascular remodeling induced by passive smoking

Coronary heart disease (CHD) is the most common cause of death in many developed countries. The major risk factors for CHD are smoking, high blood pressure, diabetes, high cholesterol levels, and lack of physical activity. Importantly, passive smoke also increases the risk for CHD. The mechanisms involved in the effects of passive smoke in CHD are complex and include endothelial dysfunction, lipoprotein modification, increased inflammation and platelet activation. Recently, several studies have shown that exposure to tobacco smoke can result in cardiac remodeling and compromised cardiac function. Potential mechanisms for these alterations are neurohumoral activation, oxidative stress, and MAPK activation. Although the vascular effects of cigarette smoke exposure are well known, the effects of tobacco smoking on the heart have received less attention. Therefore, this review will focus on the recent findings as to the effects of passive smoking in acute and chronic phases of vascular and cardiac remodeling. © 2009 Bentham Science Publishers Ltd.

Efeito da exposição à fumaça de cigarro durante a prenhez e a lactação de ratas e sua prole sobre parâmetros séricos e morfométricos

PURPOSE: to investigate the effect of cigarette smoke exposure on body and tissue weight gain, serum parameters and milk yield during pregnancy and lactation in rats, and the impact on offspring from birth toil young adulthood. METHODS: 40 Wistar pregnant rats were randomly divided into: CG - not exposed to cigarette smoke and sacrificed at the end of pregnancy; CL - not exposed to cigarette smoke and sacrificed at the end of lactation; FG - exposed to cigarette smoke and sacrificed at the end of pregnancy; FL - exposed to cigarette smoke and sacrificed at the end of lactation. The offspring were separated by gender and divided according to their mothers' groups. Tissue weight, body weight and serum parameters were evaluated in rats and offspring. Milk yield per pup was calculated. RESULTS: body weight was decreased in FL during lactation (CL=267.0±7.2; FL=235.5±7.2 g*, *p<0.05). Adipose tissue was not detected in the CL and FL groups, and was reduced in FG compared to CG (CG=3.3±0.3; FG=2.4±0.3 g*, *p<0.05). Rats exposed to cigarette smoke had higher blood glucose levels (CG=113±17, CL=86±16, FG=177±21*, FL=178±23 mg/dL*, *p<0.05 CG versus FG e CL versus FL), CL and FL groups presented lower HDL-cholesterol with no change in total cholesterol. Finally, rats exposed to cigarette smoke had lower milk yield compared to unexposed rats (CL=6.7±0.4, FL=5.4±0.3 g*, *p<0.05). In offspring from the FG and FL groups, there was a decrease of body weight from birth to young adulthood, with no changes in gastrocnemius, liver or heart weights in any group, and adipose tissue was no detected in female offspring. There was an increase in blood glucose in offspring of both sexes from rats exposed to cigarette smoke (males: Pcg=107±10.5, Pcl=115±8.6, Pfg=148±16.8*, Pfl=172±11.2**; females: Pcg=109±27.2, Pcl=104±9.7, Pfg=134±20.0*, Pfl=126±13.3**; p<0.05 *Pcg versus Pfg and **Pcl versus Pfl). CONCLUSIONS: exposure to cigarette smoke provokes impairment of morphometric and serum parameters during pregnancy and lactation both in mothers and offspring, which is maintained during young adulthood.

Cardiac remodeling induced by smoking: Concepts, relevance, and potential mechanisms

Cardiac or ventricular remodeling is characterized by molecular, cellular, and interstitial alterations that lead to changes in heart size, mass, geometry and function in response to a given insult. Currently, tobacco smoke exposure is recognized as one of these insults. Indeed, tobacco smoke exposure induces the enlargement of the left-sided cardiac chambers, myocardial hypertrophy, and ventricular dysfunction. Potential mechanisms for these alterations include hemodynamic and neurohormonal changes, oxidative stress, inflammation, nitric oxide bioavailability, matrix metalloproteinases and mitogen-activated protein kinase activation. This review will focus on the concepts, relevance, and potential mechanisms of cardiac remodeling induced by tobacco smoke. © 2012 Bentham Science Publishers.

Smoking is associated with remodeling of gap junction in the rat heart: Smoker's paradox explanation?

Background: In a previous study utilizing the rat model, exposure to tobacco smoke for 5 weeks increased survival after AMI, despite similar age and infarct size between the smokers and nonsmokers, and absence of reperfusion. Objective: Thus, this study aimed to analyze the effects of exposure to tobacco smoke on intensity, distribution or phosphorylation of connexin 43 in the rat heart. Methods: Wistar rats weighing 100 g were randomly allocated into 2 groups: 1) Control (n = 25); 2) Exposed to tobacco smoke (ETS), n = 23. After 5 weeks, left ventricular morphometric analysis, immunohisthochemistry and western blotting for connexin 43 (Cx43) were performed. Results: Collagen volume fraction, cross-sectional areas, and ventricular weight were not statistically different between control and ETS. ETS showed lower stain intensity of Cx43 at intercalated disks (Control: 2.32 ± 0.19; ETS: 1.73 ± 0.18; p = 0.04). The distribution of CX43 at intercalated disks did not differ between the groups (Control: 3.73 ± 0.12; ETS: 3.20 ± 0.17; p = 0.18). ETS rats showed higher levels of dephosphorylated form of Cx43 (Control: 0.45 ± 0.11; ETS: 0.90 ± 0.11; p = 0.03). On the other hand, total Cx43 did not differ between control and ETS groups (Control: 0.75 ± 0.19; ETS: 0.93 ± 0.27; p = 0.58). Conclusion: Exposure to tobacco smoke resulted in cardiac gap junction remodeling, characterized by alterations in the quantity and phosphorylation of the Cx43, in rats hearts. This finding could explain the smoker's paradox observed in some studies.

Influência da suplementação de vitamina D na dieta sobre remodelação cardíaca em ratos expostos à fumaça do cigarro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Função testicular de raos expostos à fumaça do cigarro e possível papel protetor do zinco: análises seminais, morfológicas e moleculares

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência da taurina na remodelação cardíaca induzida pela exposição à fumaça do cigarro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência da suplementação de ácido retinóico no processo de remodelação cardíaca induzida pela exposição à fumaça do cigarro em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)