Diversos estudos relatam os efeitos da exposição à nicotina nos períodos pré e pós-natal, contudo, pouco se sabe a respeito dos efeitos da fumaça do cigarro na cascata de eventos que caracteriza o desenvolvimento do sistema nervoso central (SNC). Neste contexto, o objetivo deste trabalho foi esclarecer se a exposição à fumaça do cigarro no início do período pós-natal induz prejuízo ao desenvolvimento do SNC na infância, e as possíveis consequências na adolescência e na fase adulta. Camundongos BALB/c foram expostos a uma mistura de fumaça central e lateral do cigarro referência 3R4F (Universidade de Kentucky, EUA), desde o 3° dia de vida pós-natal (P) até P14 por duas horas diárias. Nossos resultados indicam que a exposição à fumaça do cigarro no início do período pós-natal induz prejuízo ao processo de aprendizado e memória e aumento na ansiedade em todas as idades avaliadas, além de induzir diminuição da atividade locomotora na infância e na adolescência. Ainda, observamos diminuição dos níveis de BDNF e das proteínas sinápticas sinapsina e sinaptofisina no hipocampo, cerebelo, córtex pré-frontal e estriado. A fumaça do cigarro também induz diminuição na porcentagem de fibras mielinizadas no nervo óptico e aumento da proteína básica de mielina (PBM) no cerebelo na infância, além de diminuição da PBM no telencéfalo e tronco encefálico na adolescência e no cerebelo na fase adulta. Nossos resultados sugerem que a exposição à fumaça do cigarro no início do período pós-natal causa prejuízo ao desenvolvimento do SNC, sendo que não há reversão dos efeitos observados no aprendizado e memória ou mesmo nos níveis de proteína pré-sináptica na adolescência e na fase adulta. / Several studies show the effects of nicotine exposure during pre- and postnatal period. However, little is known about the effects of environmental tobacco smoke (ETS) in the cascade of events that characterizes the brain development. Thus, the aim of this study was to evaluate the effects of ETS in early brain development. BALB/c mice were exposed to a mixture of mainstream and sidestream of tobacco smoke of reference cigarettes 3R4F (University of Kentucky, EUA) from the 3rd (P3) to the 14th (P14) day of life, during 2h/day. Our results showed that ETS induced impairment in learning and memory and increased anxiety in all the ages evaluated. In addition, there was a decrease in locomotor activity during childhood and adolescence. ETS also induced impairment in synaptic transmission, by a decrease in synapsin, synaptophysin and BDNF in hippocampus, cerebellum and prefrontal cortex as compared to the control group. The percentage of myelinated fibers in the optic nerve in childhood and in myelin basic protein (MBP) in the telencephalon and brainstem were lower in adolescents mice exposed to ETS when compared to the control group. In cerebellum, there was an increase in MBP in infants and a decrease in adults compared to the control group. Taken all together, our results suggest that the exposure to ETS in the early postnatal period induces impairment to the brain development. It is noteworthy that the effects on learning and memory or even in the presynaptic protein levels were not reversed in adolescence and adulthood.

Tobacco smoke particulate matter (PM) is a complex mixture of condensed organic compounds, with about 5 to 10% water. Its general properties are similar in some respects to that of atmospheric organic aerosol PM and thus provides a useful surrogate when studying atmospheric PM. Due to its ability to undergo acid-base chemistry, nicotine is of particular interest in the tobacco smoke system. The gas/particle partitioning of nicotine depends on the protonation state of nicotine in the particles, so the distribution of nicotine between these phases provides a means of understanding the acid-base balance in the tobacco smoke system. The goal of this work is to develop an acid-base balance for mainstream tobacco smoke that accounts for the extent of protonation of nicotine. Samples of extracted smoke particulate matter from seven brands of cigarettes were analyzed by ion chromatography (IC) and titration by both acid (HCl) and base (lithium phenoxide) for comparison with nicotine data collected by colleagues. IC analysis was used to quantify tracers of known acidic and basic species in tobacco smoke. Anion tracers for acids included: glycolate, acetate, formate, lactate, chloride, nitrite, sulfate, and nitrate. The cation tracers for base were ammonium, sodium, and potassium. The tobacco smoke extracts were also analyzed after acidification by the HCl titrant for changes in ammonia and organic acid concentrations to determine whether "bound" forms of these compounds were present in the PM. The titration data provided total concentrations of weak acid and bases in the samples. This titration data was compared with the concentrations of the tracers for weak acids and bases (along with the quantification of total nicotine by colleagues) to determine whether the IC analyses were accounting for all of the important species. The results of this comparison show that these analyses missed relevant species in the tobacco smoke system. As tobacco smoke PM is a complex organic mixture, the ability of acid species to protonate nicotine will be different than in aqueous media. The acidic species of interest were assumed to be either strong or weak, with the strong species assumed to be fully ionized after protonation of nicotine. Some portion of the weak acid species could then protonate any available nicotine. An electroneutrality equation (ENE) was developed for the tobacco smoke PM and populated using the IC data and the nicotine data obtained by colleagues. Using this ENE, the extent ionization of the weak acids species (α1A) and the net reaction constant for the protonation of nicotine by these weak acids (K*) was estimated. However, interpretation of the results were complicated by the underrepresentation of the pertinent weak acid species in our IC analyses. This study concluded that further work is needed to identify the missing weak acid and base species to obtain a better representation of the acid-base balance in tobacco smoke PM and to understand the ability of these weak acid species to protonate nicotine.

Polycyclic aromatic hydrocarbons (PAHs) are environmental and occupational carcinogens that are produced by the incomplete combustion of organic material, such as from the burning of tobacco, coal, and petroleum products. In addition to causing cancer, exposure to PAHs is hypothesized to contribute to atherosclerosis and to lead to increased incidence rates of cardiovascular disease in populations. Considering the number of deaths attributable to tobacco smoke exposure, ambient air pollution, and occupational hazards, PAHs may be a significant contributor to the prevalence of cardiovascular disease in human populations. However, a clear exposure-response relationship between PAHs and measures of cardiovascular disease has not been demonstrated. While PAH exposure has been shown to be associated with indicators of cardiovascular disease in research animals, this relationship has not been studied comprehensively in human populations. Using data from the continuous National Health and Nutrition Examination Surveys (NHANES) 1999 - 2004 of a representative sample of the entire US civilian population, this study investigated predictors of total body burden of PAHs and associations between urinary metabolites of PAHs and biomarkers of cardiovascular disease in 4,492 study participants aged 20 years and older. Using various analytic approaches, this research project identified tobacco smoke exposure as a significant predictor of urinary levels of low molecular weight PAHs but not as a predictor of urinary levels of high molecular weight PAHs in a large population of individuals without known occupational exposure to PAHs. Worker occupational category was not associated with urinary levels of any PAH metabolites. The results of this study also indicate a possible association between exposure to PAHs and the development of cardiovascular disease in humans. Levels of multiple metabolites of specific PAHs, naphthalene, fluorene, and phenanthrene were significantly associated with increases in total cholesterol, triglycerides, WBC count, and C-reactive protein levels. Additionally, this study examined the utility of factor analysis for data reduction of 23 urinary PAH metabolites to two latent factors representing low and high molecular weight PAHs to streamline investigations of the associations of PAH exposures with various health outcomes. Results of this study suggest mechanisms by which PAH exposure contributes to the burden of cardiovascular disease on human populations and the methods by which human body burden on PAHs can be measured.

Adverse health effects in children caused by environmental tobacco smoke (ETS) are well known. Children are primarily exposed by their parents’ smoking in their homes. A comprehensive evidence base shows that parental smoking during pregnancy and ETS exposure in early childhood are associated with an increased risk for a range of adverse health problems. Child Health Care nurses, who meet nearly all families in Sweden with children aged 0-6 years, have thus an important role in tobacco preventive work in order to support parents in their ambitions to protect their children from ETS exposure. The overall aim of this thesis was to develop, test and evaluate a new model for tobacco preventive work in Child Health Care (CHC) with special focus on areas with a high prevalence of parental smoking. In a first step CHC nurses’ and parents’ views on tobacco preventive work were analysed in two studies based on questionnaires. The intervention was performed during the second step, based on the results from nurses’ and parents’ experience of the tobacco preventive work in CHC, and with methods from Quality Improvement. An “intervention bundle” was developed which included evidence based methods for prevention of ETS exposure, and four learning sessions for the nurses. The instrument “Smoking in Children’s Environment Test” (SiCET) included in the bundle was evaluated with focus group interviews with the CHC nurses who participated in the intervention. Two urine samples were analysed to measure cotinine levels in children which provide an estimate for ETS exposure. Parents’ answers from the SiCET questionnaire, measurements of cotinine, and data from the nurses’ log-books were used in the evaluation of the effects of the intervention. In areas with a high prevalence of parental smoking 22 nurses recruited 86 families of whom 72 took part for the entire one-year period of the intervention. The results showed that parents wanted to have information on the harmful effects tobacco smoke have on their children and how they can protect their children from ETS exposure. The nurses saw tobacco preventive work as important but they experienced difficulties to reach certain groups such as fathers, foreign-born parents, and those who are socio-economically disadvantaged. The SiCET instrument provided a basis for dialogue with parents. The main results from the intervention showed that ten parents (11%) quit smoking, thirty-two families (44%) decreased their cigarette consumption in the home, and fewer children were exposed to tobacco smoke. Consequently, more children showed levels of urinary cotinine less than 6 ng/ml (base-line n=43, follow up n=54; p=0.05). The total number of outdoor smokers did not change. Seven of the nurses (30%) had successful results in their areas with a decrease of smokers in families with a child of 8 months, from 20% in 2009 to 12% in 2011. The corresponding figures for the whole county as well as the country did not decrease during the same period. The sustainability of the intervention has to be followed and thus measures should be followed prospectively over time. The SiCET instrument was found useful and might be applicable in other arenas where children’s ETS exposure is discussed. The development of an instant cotinine test using dipsticks would make it possible to give parents immediate feedback on the effectiveness of taken protective actions. This could work as a pedagogic resource in the dialogue with parents.

! BACKGROUND: Exposure to Environmental Tobacco Smoke (ETS) is elevating blood levels of inflammatory mediators and chemoattractants which seem to play an important role in the development of several diseases (e.g. Chronic Obstructive Pulmonary Disease). First evidences showed that men and women might differ in their proneness for these diseases. The aim of this study was to investigate whether there are effects of ETS during pregnancy on inflammatory cytokines in cord blood and in mother’s blood and if there are any differences between male and female newborns. METHODS: Within the LiNA (Lifestyle and environmental factors and their influence on Newborn Allergy Risk) study, whole blood samples of 460 mother-child pairs were analyzed for the concentrations of IL-6, IL-8, IL-10, IL-12, IL-4, IL-5, INF-gamma, TNF-alpha and MCP-1 using cytrometic bead asseys. The association between ETS exposure and cytokines was calculated using the Mann-Whitney-U-test and adjusted with a multiple regression model for parental atopy, parental education status and cat ownership. The exposure assessment is based on questionnaire data on smoking behaviour of the parents and measurement of indoor benzene concentration. RESULTS: Female newborn, being exposed in utero to 10 cigarettes a day or more, had significantly higher blood concentrations of IL-8, IL-6 and MCP-1 whereas there have been no elevations in male newborn being exposed to the same amount of cigarettes. Furthermore a significantly decreased amount of INF-gamma was found in cord blood of male newborns but not in female newborns. General increasing levels of TNF-alpha in cord blood where found for daily smoke exposure without relating it to the exact number of cigarettes. CONCLUSION: The data of this study refer to gender-specific differences in the susceptibility to ETS exposure. The induction of inflammatory signals in cord blood in response to cigarette smoke exposure is stronger in female than in male newborn. / Die vorliegende Arbeit ist Teil einer umweltepidemiologischen Kohortenstudie (LiNA), in der der Einfluss von Umwelt- und Lebensbedingungen auf die Entwicklung von Immunsystem und Allergien bei Neugeborenen unter Einbezug der vorgeburtlichen Zeit untersucht wird. In welchem Maße sich eine Rauchbelastung während der Schwangerschaft auf die Zytokinmuster der Neugeborenen im Nabelschnurblut auswirkt und inwiefern dies mit dem Zytokinmuster der Mutter korreliert, sollte das Ziel dieser Dissertation sein. Dafür wurden Daten von insgesamt 629 Mutter-Kind-Paaren erhoben, Zytokin- und Chemokinbestimmungen, sowie die des Gesamt-IgE aus den Blutproben der 34. SSW und denen der Nabelschnur vorgenommen. Interessanterweise konnten geschlechterspezifische Unterschiede im Zytokinspektrum der Neugeborenen gefunden werden. Bei den weiblichen Neugeborenen zeigte sich eine deutliche Erhöhung proinflammatorischer Marker, wenn deren Mütter dem Rauch von mehr als 10 Zigaretten pro Tag ausgesetzt waren. Dieser Anstieg war weder im Blut der männlichen Neugeborenen noch im Blut der Schwangeren in der 34. SSW zu beobachten. Zusätzlich konnte beobachtet werden, dass auch einzig die männlichen Neugeborenen stark negativ mit ihrer IFN-gamma-Produktion auf die passive Rauchbelastung reagieren. Die mit dieser Arbeit ermittelten Daten, dass das Immunsystem beim Neugeborenen geschlechterspezifisch unterschiedlich auf Tabakrauch zu reagieren scheint, sind erstmals in der Literatur zu finden. Die Erforschung des Immunsystems und dessen Beteiligung an zahlreichen Erkrankungen, besonders den chronisch Inflammatorischen, ist durchaus relevant im medizinischen Alltag. Diese Arbeit trägt einen weiteren Baustein dazu bei und gibt Anstoß für weitere Studien.

Smoking and environmental tobacco smoke (ETS) exposure are major risk factors for cardiovascular disease (CVD), although the exact components and pathophysiological mechanisms responsible for this association remain unclear. Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are ubiquitous environmental contaminants that form during organic material combustion and are thus found in cigarette smoke, vehicle exhaust particles, and air pollution. We hypothesize that PAHs are key agents responsible for mediating the cigarette smoke effects in the cardiovascular system, including increased oxidative stress, inflammation, and arterial stiffness.<p> Arterial stiffness is a powerful, independent predictor of cardiovascular risk and is regulated, in part, by vasoactive mediators derived from the endothelium. The first objective of this project was to determine whether pulse wave dP/dt collected from radiotelemetry-implanted rats is a reliable indicator of changes in arterial stiffness following administration of vasoactive drugs or acute ETS exposure. Anaesthetized rats were administered a single dose of saline (vehicle control), acetylcholine, norepinephrine, and N(G)-nitro-L-arginine methyl ester (L-NAME) via the tail vein, allowing a washout period between injections. Acetylcholine decreased and norepinephrine increased dP/dt compared to saline vehicle. Injection of the nitric oxide (NO) synthase inhibitor L-NAME decreased plasma nitrate/nitrite (NOx), but transiently increased dP/dt. For the ETS experiment, rats were exposed for one hour to sham, low dose ETS, or high dose ETS. Exposure to ETS did not significantly alter dP/dt or plasma endothelin-1 (ET-1) levels, but increased plasma NOx levels at the high ETS exposure and increased plasma nitrotyrosine levels in both ETS groups. In conclusion, acute changes in NO production via acetylcholine or L-NAME alter the arterial pulse wave dP/dt consistently with the predicted changes in arterial stiffness. Although acute ETS appears to biologically inactivate NO, a concomitant increase in NO production at the high ETS exposure may explain why ETS did not acutely alter dP/dt.<p> The second objective of this project was to compare the effects of subchronic ETS and BaP exposure on circadian blood pressure patterns, arterial stiffness, and possible sources of oxidative stress in radiotelemetry-implanted rats. Pulse wave dP/dt was used as an indicator of arterial stiffness, and was compared to both structural (wall thickness) and functional (NO production and bioactivity, ET-1 levels) features of the arterial wall. In addition, histology of lung, heart, and liver were examined as well as pulmonary and hepatic detoxifying enzyme activity (cytochrome P450 specifically CYP1A1). Daily ETS exposure for 28 days altered the circadian pattern of heart rate and blood pressure in rats, with a loss in the normal dipping pattern of blood pressure during sleep. Subchronic ETS exposure also increased dP/dt in the absence of any structural modifications in the arterial wall. Although NO production and ET-1 levels were not altered by ETS, there was increased biological inactivation of NO via peroxynitrite production (as indicated by increased plasma nitrotyrosine levels). Thus, vascular stiffness and failure of blood pressure to dip precede structural changes in rats exposed to ETS for 28 days. Exposure to ETS also caused increased number of lung neutrophils as well as increased CYP1A1 activity in lung microsomes.<p> Since ETS-induced increases in arterial stiffness occurred as early as day 7, radiotelemetry-implanted rats were exposed daily to intranasal BaP for 7 days. Similar to ETS, BaP exposure altered circadian blood pressure patterns and reduced blood pressure dipping during sleep. Thus, in support of part of our hypothesis, the PAH component of cigarette smoke may be responsible for the ETS-induced increase in blood pressure and the loss of dipping pattern during sleep. Increased neutrophil recruitment was observed in the lungs of both ETS- and BaP-exposed rats, suggesting that lung inflammatory reactions may be involved in the disruption of circadian blood pressure rhythms. Unlike ETS however, BaP exposure did not significantly alter pulse wave dP/dt, endothelial function, or lung CYP1A1 activity. Thus, contrary to our hypothesis, the reduction in NO bioactivity and increased arterial stiffness caused by ETS cannot be explained by BaP at the dose and length of the exposure in the current study. Production of reactive metabolites in the lung following ETS exposure may be responsible, at least in part, for the increases in oxidative stress in the vasculature, leading to reduced NO bioactivity and increased arterial stiffness. Oxidative stress caused by BaP exposure may have been insufficient to reduce NO bioactivity in the peripheral vasculature. Therefore arterial stiffness was not increased and factors other than NO may be responsible for the increase in blood pressure observed with ETS and BaP exposure.

Introduction: Despite the known consequences of cigarette smoking, almost 20% of adults in the United States smoke. Smoking has been shown to harm nearly every organ of the body. Its detrimental effects have been seen not only in smokers themselves but also in those exposed to secondhand smoke (SHS) at work and in other public places. Methodology: The purpose of this thesis was to examine compliance with the signage requirement of the Georgia Smokefree Air Act (GSAA) of 2005 among 99 hospitality venues located in Atlanta. Photographs of bars and restaurant entrances were taken and raters then classified each venue as compliant or non-compliant with smoking status signage requirements of the GSAA. Additionally, air samples were collected using Sidepak equipment from 59 venues in order to estimate the PM2.5 levels, which is a recognized measure of air quality. With Spearman’s rho correlation coefficient (r), analyses were run to determine correlations between signage compliance, number of cigarettes being smoked, and smoking permitted with air quality (PM2.5). Analyses were conducted using the Statistical Package for Social Sciences (SPSS) version 19. Results: Of the 99 venues assessed, only 21 (21.2 %) complied with the signage requirements of the GSAA. Venues that do adhere to signage requirements and indicate no smoking on their signs and at the same time via telephone stated that smoking is prohibited had the lowest PM2.5 levels =15.03. On the contrary, those venues that display signs permitting smoking and via telephone indicated smoking is allowed had the highest PM2.5 levels =230.31. It was determined that there is a strong positive correlation between PM2.5 and “number of cigarettes” (r=.611, n=59, p<.001) as well as moderate correlation between PM2.5 and “smoking permitted” as indicated from phone calls (r=.464, n=59, p<.001). However, analysis showed a weak correlation between PM2.5 and “signage compliance” in accordance with GSAA (r=.107, n=59, p>.001). Conclusions: Enforcement of GSAA must be enhanced in order to better protect workers and patrons of Atlanta’s bars and restaurants from harmful exposure to SHS. Findings from this study support that prohibiting smoking in bars and restaurants and having signs stating that smoking is prohibited would improve air quality and protect workers by eliminating their exposure to SHS while working.

Smoking and environmental tobacco smoke (ETS) exposure are major risk factors for cardiovascular disease (CVD), although the exact components and pathophysiological mechanisms responsible for this association remain unclear. Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are ubiquitous environmental contaminants that form during organic material combustion and are thus found in cigarette smoke, vehicle exhaust particles, and air pollution. We hypothesize that PAHs are key agents responsible for mediating the cigarette smoke effects in the cardiovascular system, including increased oxidative stress, inflammation, and arterial stiffness.<p> Arterial stiffness is a powerful, independent predictor of cardiovascular risk and is regulated, in part, by vasoactive mediators derived from the endothelium. The first objective of this project was to determine whether pulse wave dP/dt collected from radiotelemetry-implanted rats is a reliable indicator of changes in arterial stiffness following administration of vasoactive drugs or acute ETS exposure. Anaesthetized rats were administered a single dose of saline (vehicle control), acetylcholine, norepinephrine, and N(G)-nitro-L-arginine methyl ester (L-NAME) via the tail vein, allowing a washout period between injections. Acetylcholine decreased and norepinephrine increased dP/dt compared to saline vehicle. Injection of the nitric oxide (NO) synthase inhibitor L-NAME decreased plasma nitrate/nitrite (NOx), but transiently increased dP/dt. For the ETS experiment, rats were exposed for one hour to sham, low dose ETS, or high dose ETS. Exposure to ETS did not significantly alter dP/dt or plasma endothelin-1 (ET-1) levels, but increased plasma NOx levels at the high ETS exposure and increased plasma nitrotyrosine levels in both ETS groups. In conclusion, acute changes in NO production via acetylcholine or L-NAME alter the arterial pulse wave dP/dt consistently with the predicted changes in arterial stiffness. Although acute ETS appears to biologically inactivate NO, a concomitant increase in NO production at the high ETS exposure may explain why ETS did not acutely alter dP/dt.<p> The second objective of this project was to compare the effects of subchronic ETS and BaP exposure on circadian blood pressure patterns, arterial stiffness, and possible sources of oxidative stress in radiotelemetry-implanted rats. Pulse wave dP/dt was used as an indicator of arterial stiffness, and was compared to both structural (wall thickness) and functional (NO production and bioactivity, ET-1 levels) features of the arterial wall. In addition, histology of lung, heart, and liver were examined as well as pulmonary and hepatic detoxifying enzyme activity (cytochrome P450 specifically CYP1A1). Daily ETS exposure for 28 days altered the circadian pattern of heart rate and blood pressure in rats, with a loss in the normal dipping pattern of blood pressure during sleep. Subchronic ETS exposure also increased dP/dt in the absence of any structural modifications in the arterial wall. Although NO production and ET-1 levels were not altered by ETS, there was increased biological inactivation of NO via peroxynitrite production (as indicated by increased plasma nitrotyrosine levels). Thus, vascular stiffness and failure of blood pressure to dip precede structural changes in rats exposed to ETS for 28 days. Exposure to ETS also caused increased number of lung neutrophils as well as increased CYP1A1 activity in lung microsomes.<p> Since ETS-induced increases in arterial stiffness occurred as early as day 7, radiotelemetry-implanted rats were exposed daily to intranasal BaP for 7 days. Similar to ETS, BaP exposure altered circadian blood pressure patterns and reduced blood pressure dipping during sleep. Thus, in support of part of our hypothesis, the PAH component of cigarette smoke may be responsible for the ETS-induced increase in blood pressure and the loss of dipping pattern during sleep. Increased neutrophil recruitment was observed in the lungs of both ETS- and BaP-exposed rats, suggesting that lung inflammatory reactions may be involved in the disruption of circadian blood pressure rhythms. Unlike ETS however, BaP exposure did not significantly alter pulse wave dP/dt, endothelial function, or lung CYP1A1 activity. Thus, contrary to our hypothesis, the reduction in NO bioactivity and increased arterial stiffness caused by ETS cannot be explained by BaP at the dose and length of the exposure in the current study. Production of reactive metabolites in the lung following ETS exposure may be responsible, at least in part, for the increases in oxidative stress in the vasculature, leading to reduced NO bioactivity and increased arterial stiffness. Oxidative stress caused by BaP exposure may have been insufficient to reduce NO bioactivity in the peripheral vasculature. Therefore arterial stiffness was not increased and factors other than NO may be responsible for the increase in blood pressure observed with ETS and BaP exposure.

Thesis--University of Oklahoma. / Bibliography: leaves 137-141.

Thesis (M.P.H.)--University of Adelaide, Dept. of Public Health, 2001. / Bibliography: leaves 92-98.