This report focuses on change over time in tobacco use among adolescents in countries included in the Eastern Mediterranean Region (EMR) of the World Health Organization. The Global Youth Tobacco Survey (GYTS) was conducted in each site at least twice between 1999 and 2007. Results indicate that for students aged 13-15 years tobacco use is a major public health problem. Increase in the use of water pipe, the likely initiation of smoking by never smokers, and a potential increase in tobacco use among young girls was found in most of the EMR sites. The results from the GYTS can be used by all of the EMR countries involved to set their tobacco control programme and policy agenda
Home smoking bans significantly reduce secondhand smoke exposure among children, but parents may offer discordant reports on whether there is a home smoking ban. The purpose of this study was to examine national trends in (a) parental discordance/concordance in the reporting of home smoking bans and (b) correlates of discordant/concordant reports among two-parent households with underage children from 1995 to 2007. Data from the 1995/1996, 1998/1999, 2001/2002, 2003, and 2006/2007 Tobacco Use Supplement of the U.S. Current Population Survey were used to estimate prevalence rates and multinomial logistic regression models of discordant/concordant parental smoking ban reports by survey period. Overall, the percentage of households in which the 2 parents gave discordant reports on a complete home smoking ban decreased significantly from 12.7% to 2.8% from 1995 to 2007 (p < .001). Compared with households where both parents reported a complete smoking ban, discordant reports were more likely to be obtained from households with current smokers (p < .01) across survey periods. Compared with households where both parents reported the lack of a complete home smoking ban, discordant reports were more likely among households with college graduates, no current smokers, and parents with Hispanic ethnicity (p < .05). Parental concordance on the existence of a home smoking ban increased from 1995 to 2007. This suggests estimates of home smoking bans based on just one parent may be more reliable now than they were in the past. Interventions to improve the adoption and enforcement of home smoking bans should target households with current smoker parents.
Abstract Raloxifene is a 2nd-generation selective estrogen receptor modulator used for the prevention and treatment of osteoporosis and the prevention of breast cancer in postmenopausal women. Raloxifene is extensively metabolized by glucuronidation to form raloxifene-6-glucuronide (ral-6-Gluc) and raloxifene-4’-glucuronide (ral-4’-Gluc). The goal of the present study was to determine whether functional polymorphisms in active UGTs could play a role in altered raloxifene glucuronidation in vivo. Using homogenates from HEK293 UGT-overexpressing cell lines, raloxifene was shown to be glucuronidated primarily by the hepatic UGTs 1A1 and 1A9 and the extra-hepatic UGTs 1A8 and 1A10; no detectable raloxifene glucuronidation activity was found for UGT2B enzymes. Functional UGT1A1 transcriptional promoter genotypes were significantly (ptrend=0.005) associated with ral-6-Gluc formation in human liver microsomes, and, consistent with the decreased raloxifene glucuronidation activities observed in vitro with cell line over-expressing UGT1A8 variants, the UGT1A8*2 variant was significantly (p=0.023) correlated with total raloxifene glucuronide formation in human jejunum homogenates. While ral-4’-Gluc exhibited 1/100th the anti-estrogenic activity of raloxifene itself as measured by binding to the estrogen receptor, raloxifene glucuronides comprised ∼99% of the circulating raloxifene dose in raloxifene-treated subjects, with ral-4’-Gluc comprising ∼70% of raloxifene glucuronides. Plasma ral-6-Gluc (ptrend=0.0025), ral-4’-Gluc (ptrend=0.001), and total raloxifene glucuronides (ptrend=0.001) were increased in raloxifene-treated subjects who were predicted slow metabolizers [UGT1A8 (*1/*3)] vs intermediate metabolizers [UGT1A8 (*1/*1) or UGT1A8 (*1/*2)] vs fast metabolizers [UGT1A8 (*2/*2). These data suggest that raloxifene metabolism may be dependent on UGT1A8 genotype and that UGT1A8 genotype may play an important role in overall response to raloxifene. Citation Format: Dongxiao Sun, Nathan R. Jones, Manni Andrea, Philip Lazarus. Characterization of raloxifene glucuronidation and the role of UGT genotypes on raloxifene metabolite profiles in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2203. doi:10.1158/1538-7445.AM2013-2203
Raloxifene is a second-generation selective estrogen receptor modulator used for the prevention and treatment of osteoporosis and the prevention of breast cancer in postmenopausal women. Raloxifene is extensively metabolized by glucuronidation to form raloxifene-6-glucuronide (ral-6-Gluc) and raloxifene-4'-glucuronide (ral-4'-Gluc). The goal of the present study was to determine whether functional polymorphisms in active UGTs could play a role in altered raloxifene glucuronidation in vivo. Using homogenates from HEK293 UGT-overexpressing cell lines, raloxifene was shown to be glucuronidated primarily by the hepatic UGTs 1A1 and 1A9 and the extra-hepatic UGTs 1A8 and 1A10; no detectable raloxifene glucuronidation activity was found for UGT2B enzymes. Functional UGT1A1 transcriptional promoter genotypes were significantly (Ptrend = 0.005) associated with ral-6-Gluc formation in human liver microsomes, and, consistent with the decreased raloxifene glucuronidation activities observed in vitro with cell lines overexpressing UGT1A8 variants, the UGT1A8*2 variant was significantly (P = 0.023) correlated with total raloxifene glucuronide formation in human jejunum homogenates. While ral-4'-Gluc exhibited 1:100th the anti-estrogenic activity of raloxifene itself as measured by binding to the estrogen receptor, raloxifene glucuronides comprised about 99% of the circulating raloxifene dose in raloxifene-treated subjects, with ral-4'-Gluc comprising ~70% of raloxifene glucuronides. Plasma ral-6-Gluc (Ptrend = 0.0025), ral-4'-Gluc (Ptrend = 0.001), and total raloxifene glucuronides (Ptrend = 0.001) were increased in raloxifene-treated subjects who were predicted slow metabolizers [UGT1A8 (*1/*3)] versus intermediate metabolizers [UGT1A8 (*1/*1) or UGT1A8 (*1/*2)] versus fast metabolizers [UGT1A8 (*2/*2). These data suggest that raloxifene metabolism may be dependent on UGT1A8 genotype and that UGT1A8 genotype may play an important role in overall response to raloxifene.
The sourcing lifetimes, microstructural stability, and diffusion performance of a new solid planar phosphorus source for silicon doping were investigated in the temperature range 900°–1100°C. The source wafers were highly porous ceramic wafers containing as the "active" component in an inert refractory binder matrix. The microstructural stability and thermogravimetric analysis (TGA) results indicated the structural integrity and sourcing ability of this material at temperatures of at least 1050°C. Theoretical lifetimes of 260 and 3400 hr at 1100° and 900°C, respectively, have been predicted from the TGA results. Experimental data relating sheet resistance, junction depth, and diffusion coefficient for silicon wafers doped using these source wafers are presented. Special material handling procedures are also described.
The UDP-glucuronosyltransferase (UGT) 2B subfamily of enzymes plays an important role in the metabolism of numerous endogenous and exogenous compounds, including various carcinogens present in tobacco smoke. The goal of the present study was to examine the levels of expression of individual UGT2B genes in various tissues that are targets for tobacco carcinogenesis. Using MT-ATP6 as the experimentally validated housekeeping gene, the highest extrahepatic expression of UGT2B genes was observed in human tonsil, with UGT2B expression levels similar to that observed in human liver. UGT2B17 exhibited high relative expression in most tissues examined, including lung, most tissues of the aerodigestive tract, and pancreas. UGT2B7 expression was highest in pancreas but low or undetectable in most other tissues examined. UGT2B10 expression was high in both tonsil and tongue. There was wide variability between individuals in the magnitude of expression in each tissue site, and there were strong correlations between UGT2B expression levels in different individuals within many of the tissue sites, suggesting coordinated regulation of UGT2B gene expression in extrahepatic tissues. In the liver, UGTs 2B4, 2B7, 2B10, and 2B15 were significantly correlated with each other (all r2 > 0.70, P < 0.0001). In all examined tissues of the aerodigestive tract, UGTs 2B10, 2B11, and 2B17 exhibited a strong correlation with each other (all r2 > 0.75, P < 0.05). UGTs 2B7 and 2B10 exhibited a strong inverse correlation in the pancreas (r2 = –0.95, P < 0.01). These data suggest that specific UGT2B enzymes important in tobacco carcinogen metabolism are expressed and coordinately regulated in various target sites for tobacco-related cancers.
We examined national trends in smoke-free home rules among U.S. veterans and nonveterans.We used data from the 2001-2002 and 2010-2011 Tobacco Use Supplement to the Current Population Survey to estimate and compare the existence of smoke-free home rules among veterans and nonveterans for each survey period.The prevalence of a complete smoke-free home rule among veterans increased from 64.0% to 79.7% between 2001 and 2011 (P < .01) but was consistently lower than were rates estimated for nonveterans (67.6% and 84.4%, respectively). Disparities between the 2 groups increased significantly over time (P < .05).Despite the general increase in the adoption of smoke-free home rules, veterans lag behind the rest of the U.S. population. Interventions promoting the adoption of complete smoke-free home rules are necessary to protect veterans and their families and to reduce disparities.
