Fractionation, chemical and toxicological characterization of tobacco smoke components

La fumée du tabac est un aérosol extrêmement complexe constitué de milliers de composés répartis entre la phase particulaire et la phase vapeur. Il a été démontré que les effets toxicologiques de cette fumée sont associés aux composés appartenant aux deux phases. Plusieurs composés biologiquement actifs ont été identifiés dans la fumée du tabac; cependant, il n’y a pas d’études démontrant la relation entre les réponses biologiques obtenues via les tests in vitro ou in vivo et les composés présents dans la fumée entière du tabac. Le but de la présente recherche est de développer des méthodes fiables et robustes de fractionnement de la fumée à l’aide de techniques de séparation analytique et de techniques de détection combinés à des essais in vitro toxicologiques. Une étude antérieure réalisée par nos collaborateurs a démontré que, suite à l’étude des produits de combustion de douze principaux composés du tabac, l’acide chlorogénique s’est avéré être le composé le plus cytotoxique selon les test in vitro du micronoyau. Ainsi, dans cette étude, une méthode par chromatographie préparative en phase liquide a été développée dans le but de fractionner les produits de combustion de l’acide chlorogénique. Les fractions des produits de combustion de l’acide chlorogénique ont ensuite été testées et les composés responsables de la toxicité de l’acide chlorogénique ont été identifiés. Le composé de la sous-fraction responsable en majeure partie de la cytoxicité a été identifié comme étant le catéchol, lequel fut confirmé par chromatographie en phase liquide/ spectrométrie de masse à temps de vol. Des études récentes ont démontré les effets toxicologiques de la fumée entière du tabac et l’implication spécifique de la phase vapeur. C’est pourquoi notre travail a ensuite été focalisé principalement à l’analyse de la fumée entière. La machine à fumer Borgwaldt RM20S® utilisée avec les chambres d’exposition cellulaire de British American Tobacco permettent l’étude in vitro de l’exposition de cellules à différentes concentrations de fumée entière du tabac. Les essais biologiques in vitro ont un degré élevé de variabilité, ainsi, il faut prendre en compte toutes les autres sources de variabilité pour évaluer avec précision la finalité toxicologique de ces essais; toutefois, la fiabilité de la génération de la fumée de la machine n’a jamais été évaluée jusqu’à maintenant. Nous avons donc déterminé la fiabilité de la génération et de la dilution (RSD entre 0,7 et 12 %) de la fumée en quantifiant la présence de deux gaz de référence (le CH4 par détection à ionisation de flamme et le CO par absorption infrarouge) et d’un composé de la phase particulaire, le solanesol (par chromatographie en phase liquide à haute performance). Ensuite, la relation entre la dose et la dilution des composés de la phase vapeur retrouvée dans la chambre d’exposition cellulaire a été caractérisée en utilisant une nouvelle technique d’extraction dite par HSSE (Headspace Stir Bar Sorptive Extraction) couplée à la chromatographie en phase liquide/ spectrométrie de masse. La répétabilité de la méthode a donné une valeur de RSD se situant entre 10 et 13 % pour cinq des composés de référence identifiés dans la phase vapeur de la fumée de cigarette. La réponse offrant la surface maximale d’aire sous la courbe a été obtenue en utilisant les conditions expérimentales suivantes : intervalle de temps d’exposition/ désorption de 10 0.5 min, température de désorption de 200°C pour 2 min et température de concentration cryogénique (cryofocussing) de -75°C. La précision de la dilution de la fumée est linéaire et est fonction de l’abondance des analytes ainsi que de la concentration (RSD de 6,2 à 17,2 %) avec des quantités de 6 à 450 ng pour les composés de référence. Ces résultats démontrent que la machine à fumer Borgwaldt RM20S® est un outil fiable pour générer et acheminer de façon répétitive et linéaire la fumée de cigarette aux cultures cellulaires in vitro. Notre approche consiste en l’élaboration d’une méthodologie permettant de travailler avec un composé unique du tabac, pouvant être appliqué à des échantillons plus complexes par la suite ; ex : la phase vapeur de la fumée de cigarette. La méthodologie ainsi développée peut potentiellement servir de méthode de standardisation pour l’évaluation d’instruments ou de l’identification de produits dans l’industrie de tabac.

Effect of the Concentration of Siliceous Materials Added to Tobacco Cigarettes on the Composition of the Smoke Generated during Smoking

Two as-synthesized meso- and macro-porous siliceous materials (MPSMs), i.e., Al-MCM-41 and SBA-15, were mixed with tobacco to study their effect on tobacco smoke chemistry. A reference cigarette, 3R4F, and a commercial cigarette, Fortuna, containing different percentages of MPSM were smoked in a smoking machine, and the mainstream smoke was analyzed. SBA-15 showed the highest reductions of nicotine; close to 90% when it was added at 8 mass %. The superb behavior of these materials may be related to their high particulate matter filtering efficiency in combination with their catalytic activity. The selectivity of these materials with respect to nicotine was also analyzed. Al-MCM-41 presents higher selectivity for condensed compounds than for gases, whereas SBA-15 presents similar ratios for both fractions. The highest selectivity was obtained for the liquid fraction when smoking 3R4F cigarettes mixed with Al-MCM-41.

Efeitos da exposição à fumaça de cigarro e/ou etanol durante a adolescência: alterações dos níveis de ansiedade e da atividade locomotora em camundongos durante o período de exposição e em período curto e longo de retirada

O consumo de tabaco está freqüentemente associado ao consumo de álcool e a maioria dos usuários inicia o uso e abuso destas drogas na adolescência. Como a ansiedade pode ser um fator de risco para a etiologia do uso e da retirada destas drogas, no presente estudo investigamos os efeitos da fumaça do cigarro e/ou exposição ao etanol durante a adolescência nos níveis de ansiedade ao final do período de exposição e em período curto e longo após retirada. Do 30 ao 45 dia de vida pós-natal (PN30-PN45), camundongos Suíços de ambos os sexos foram expostos a fumaça do cigarro gerada a partir da queima de cigarros para pesquisa contendo 1,7mg de nicotina 8 h/dia e/ou ao etanol (2g/kg, 25%, v/v) através de injeção intraperitoneal em dias alternados. Assim foram utilizados 4 grupos experimentais: 1) SMK+ETOH (exposição a fumaça de cigarro e injeção i.p. de etanol); 2) SMK (exposição a fumaça de cigarro e a salina i.p.); 3) ETOH (exposição a ar e injeção i.p. de etanol); 4) VEH (exposição a ar e injeção i.p. salina). Ao final do período de exposição (PN44-45) e durante a retirada de curta (PN49-50) e longa duração (PN74-75) utilizamos o Labirinto em Cruz Elevado (LCE) para avaliar os níveis de ansiedade e o Teste de Campo Aberto (CA) para avaliar os níveis de ansiedade e a atividade locomotora. Ao final do período de exposição, as fêmeas do grupo SMK apresentaram uma resposta ansiolítica no LCE. Esta resposta foi intensificada pela co-exposição ao etanol. A retirada de curto prazo da fumaça do cigarro provocou um efeito ansiogênico. Os machos do grupo ETOH apresentaram um efeito ansiogênico no LCE ao final do período de exposição, no entanto, este efeito não persistiu em um período curto de retirada. Embora nem os efeitos da fumaça de cigarro, nem os efeitos do etanol tenham persistido após um período longo de retirada, os animais do grupo SMK+ETOH apresentaram uma resposta ansiogênica no CA. Assim, nossos resultados sugerem que fêmeas adolescentes são mais susceptíveis aos efeitos ansiolíticos do fumo do tabaco. O efeito mais intenso no grupo SMK+ETOH sugere que as fêmeas co-usam estas drogas para chegar a níveis mais baixos de ansiedade. Além disso, um aumento da ansiedade após um período longo da retirada conjunta do cigarro e do etanol, pode facilitar as recaídas ao uso destas drogas.

Efeitos da exposiçao à fumaça de cigarro e a ingestão crônica de etanol sobre a mucosas da língua e da faringe: estudo histopatológico em ratos

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

How to construct a fish smoking kiln

As interest increases in fish production, fish farming is on the rise as more fish is produced in ponds, cages and tanks. However not all fish can be sold out and consumed at the same time, in addition to this, different consumers show different preference. Some individua Is tend to prefer smoked fish to fresh and fried fish. Apart from satisfying the different consumer preferences, fish smoking is important because it in creases the self life of fish, there by reducing post harvest losses. It also adds value to the fish and in this way the farmer can fetch more money from farmed products. Although the technology has been around for several years amongst the fishing communities, it is not well known amongst fish farmers. There is need to bring fish fanners on board to know how to construct the smoking kiln through the stapes out lined below.

Fusing data mining, machine learning and traditional statistics to detect biomarkers associated with depression

BACKGROUND: Atheoretical large-scale data mining techniques using machine learning algorithms have promise in the analysis of large epidemiological datasets. This study illustrates the use of a hybrid methodology for variable selection that took account of missing data and complex survey design to identify key biomarkers associated with depression from a large epidemiological study.

METHODS: The study used a three-step methodology amalgamating multiple imputation, a machine learning boosted regression algorithm and logistic regression, to identify key biomarkers associated with depression in the National Health and Nutrition Examination Study (2009-2010). Depression was measured using the Patient Health Questionnaire-9 and 67 biomarkers were analysed. Covariates in this study included gender, age, race, smoking, food security, Poverty Income Ratio, Body Mass Index, physical activity, alcohol use, medical conditions and medications. The final imputed weighted multiple logistic regression model included possible confounders and moderators.

RESULTS: After the creation of 20 imputation data sets from multiple chained regression sequences, machine learning boosted regression initially identified 21 biomarkers associated with depression. Using traditional logistic regression methods, including controlling for possible confounders and moderators, a final set of three biomarkers were selected. The final three biomarkers from the novel hybrid variable selection methodology were red cell distribution width (OR 1.15; 95% CI 1.01, 1.30), serum glucose (OR 1.01; 95% CI 1.00, 1.01) and total bilirubin (OR 0.12; 95% CI 0.05, 0.28). Significant interactions were found between total bilirubin with Mexican American/Hispanic group (p = 0.016), and current smokers (p<0.001).

CONCLUSION: The systematic use of a hybrid methodology for variable selection, fusing data mining techniques using a machine learning algorithm with traditional statistical modelling, accounted for missing data and complex survey sampling methodology and was demonstrated to be a useful tool for detecting three biomarkers associated with depression for future hypothesis generation: red cell distribution width, serum glucose and total bilirubin.

From partying to parenthood: young women's perceptions of cigarette smoking across life transitions

This study explored influences on adoption, maintenance and cessation of smoking among young women as they experienced life transitions: leaving home, gaining employment or attending college/university, marriage and parenthood. Standardized, open-ended telephone interviews were conducted with 80 women (including never smokers, continuing smokers, recent adopters and quitters) aged 24-29 years, recruited from participants in the Australian Longitudinal Study on Women's Health. The social context of smoking (socializing with other smokers, drinking alcohol and going to pubs and clubs) was perceived to be a predominant influence on smoking from the time young women left home until they settled into a committed relationship or started their own family. Stress was identified as an important factor as they experienced lifestyle changes. An increased sensitivity to the negative aspects of smoking after turning 21 was reported, and around the mid-20s the women became concerned about the addictive nature of cigarettes. Motherhood was seen to carry increased responsibilities to protect children from passive smoking and there was a perceived importance of positive role modelling to protect children from becoming smokers themselves. This study highlights the need for public health campaigns to address the social role that smoking plays in young women's lives, and the perceived use of cigarettes for stress relief. Life changes such as settling down with a partner and the contemplation of motherhood provide opportunities for targeted interventions to promote quitting.

Combination of Evolutionary Algorithms with Experimental Design, Traditional Optimization and Machine Learning

Evolutionary algorithms alone cannot solve optimization problems very efficiently since there are many random (not very rational) decisions in these algorithms. Combination of evolutionary algorithms and other techniques have been proven to be an efficient optimization methodology. In this talk, I will explain the basic ideas of our three algorithms along this line (1): Orthogonal genetic algorithm which treats crossover/mutation as an experimental design problem, (2) Multiobjective evolutionary algorithm based on decomposition (MOEA/D) which uses decomposition techniques from traditional mathematical programming in multiobjective optimization evolutionary algorithm, and (3) Regular model based multiobjective estimation of distribution algorithms (RM-MEDA) which uses the regular property and machine learning methods for improving multiobjective evolutionary algorithms.