Expression of Xenobiotic Metabolizing Enzymes in Different Lung Compartments of Smokers and Nonsmokers

BACKGROUND: Cytochrome P450 monooxygenases (CYP) play an important role in the defense against inhaled toxicants, and expression of CYP enzymes may differ among various lung cells and tissue compartments. METHODS: We studied the effects of tobacco smoke in volunteers and investigated gene expression of 19 CYPs and 3 flavin-containing monooxygenases, as well as isoforms of gluthathione S-transferases (GST) and uridine diphosphate glucuronosyltransferases (UGT) and the microsomal epoxide hydrolase (EPHX1) in bronchoalveolar lavage cells and bronchial biopsies derived from smokers (n = 8) and nonsmokers (n = 10). We also investigated gene expression of nuclear transcription factors known to be involved in the regulation of xenobiotic metabolism enzymes. RESULTS: Gene expression of CYP1A1, CYP1B1, CYP2S1, GSTP1, and EPHX1 was induced in bronchoalveolar lavage cells of smokers, whereas expression of CYP2B6/7, CYP3A5, and UGT2A1 was repressed. In bronchial biopsies of smokers, CYP1A1, CYP1B1, CYP2C9, GSTP1, and GSTA2 were induced, but CYP2J2 and EPHX1 were repressed. Induction of CYP1A1 and CYP1B1 transcript abundance resulted in increased activity of the coded enzyme. Finally, expression of the liver X receptor and the glucocorticoid receptor was significantly up-regulated in bronchoalveolar lavage cells of smokers. CONCLUSIONS: We found gene expression of pulmonary xenobiotic metabolizing enzymes and certain key transcription factors to be regulated in bronchoalveolar lavage cells and bronchial biopsies of smokers. The observed changes demonstrate tissue specificity in xenobiotic metabolism, with likely implications for the metabolic activation of procarcinogens to ultimate carcinogens of tobacco smoke

Flexural strengthening of RC continuous slab strips using NSM CFRP laminates

To assess the effectiveness of the near surface mounted (NSM) technique, in terms of load carrying and moment redistribution capacities, for the flexural strengthening of continuous reinforced concrete (RC) slabs, an experimental program was carried out. The experimental program is composed of three series of three slab strips of two equal span length, in order to verify the possibility of increasing the negative (at the intermediate support region) resisting bending moment in 25% and 50% and maintaining moment redistribution levels of 15%, 30% and 45%. Though the flexural resistance of the NSM strengthened sections has exceeded the target values, the moment redistribution was relatively low, and the increase of the load carrying capacity of the strengthened slabs did not exceed 25%. This experimental program is analyzed to highlight the possibilities of NSM technique for statically indeterminate RC slabs in terms of flexural strengthening effectiveness, moment redistribution and ductility performance. Using a FEM-based computer program, which predictive performance was appraised using the obtained experimental results, a high effective NSM flexural strengthening strategy is proposed, capable of enhancing the slab’s load carrying capacity and maintaining high levels of ductility.The study reported in this paper forms a part of the research program "CUTINEMO - Carbon fiber laminates applied according to the near surface mounted technique to increase the flexural resistance to negative moments of continuous reinforced concrete structures" supported by FCT, PTDC/ECM/73099/2006. The authors wish to acknowledge the support also provided by the S&P, Casais and Artecanter Companies. The first Author acknowledges the financial support of National Council for Scientific and Technological Development (CNPq) - Brazil, Ph.D. Grant no. 200953/2007-9. The second Author wishes to acknowledge the support provided by FCT, by means of the SFRH/BSAB/818/2008 and SFRH/BSAB/913/2009 sabbatical grants