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Sheng Yang,
Dapeng Zhang,
Youxuan Xu,
Xiaobing Wang,
Xin Liu,
Shan Wang, Jingzhu Wang,
Moutian Wu,
Zhenwen He,
Jian Zhao,
Hong Yuan
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ABSTRACT: Estrogens were prohibited in the food producing animals by European Union (96/22/EC directive) and added to the Report on Carcinogens in United States since 2002. Due to very low concentration in serum or urine (∼pg/mL), the method of control its abuse had not been fully developed. The endogenous estrogens were separated from urines of 18 adult men and women. The exogenous estrogens were chemical reference standards and over the counter preparations. Two patients of dysfunctional uterine bleeding (DUB) administered exogenous estradiol and the urines were collected for 72 hours. The urinary estrogens were separated by high-performance liquid chromatography (HPLC) and confirmed. The exogenous and exogenous estrogens were analyzed by gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) to determine the (13)C/(12)C ratio (δ(13)C ‰). The δ(13)C ‰ values of reference standard of E1, E2, and E3 were -29.36 ± 0.72, -27.98 ± 0.35, -27.62 ± 0.51, respectively. The δ(13)C ‰ values of the endogenous E1, E2, and E3 were -21.62 ± 1.07, -22.14 ± 0.98, and -21.88 ± 1.16, with P<0.01 (t-test). Two DUB patients' urinary estradiol δ(13)C ‰ values was depleted to -28.02 ± 0.33 after the administration. The progesterone, 17-hydroxyprogesterone, pregnanediol, as well as desogestrel and ethinylestradiol from contraceptives were also determined. Stable carbon isotope analysis can distinguish the endogenous and exogenous urinary estrogen in human.
Steroids 12/2012; · 2.83 Impact Factor
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ABSTRACT: Purpose: Menthol in cigarettes has been suggested to inhibit metabolism of nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The objective of this study was to investigate the glucuronide metabolite ratios (MR) for nicotine (NICGLUC/NIC), cotinine (COTGLUC/COT), trans 3'-hydroxy cotinine (3OHCOTGLUC/3OHCOT). 4-methylnitrosamino-1-(3-pyridyl)-1-butanol (NNAL - NNALGLUC/NNAL); and the ratio of trans 3'-hydroxy cotinine to cotinine (3OHCOT/COT) between adult menthol and non-menthol smokers (AS). Methods: The data was from the Total Exposure Study (TES), a stratified, multi-center, cross-sectional study that included 3,585 AS and 1,077 non-smokers. Daily urinary excretion of nicotine and five metabolites, NNAL and NNAL glucuronides, and serum cotinine were measured in the AS. The analysis included 1044 menthol (448 African-Americans, AA) and 2297 non-menthol (161 AA) AS. Results: Smoking mentholated cigarettes did not decrease any of the MR. Race was the most important significant main effect for all the MRs. AAs exhibited statistically significantly lower NICGLUC/NIC, COTGLUC/COT, NNALGLUC/NNAL and 3OHCOT/COT, but higher 3OHCOTGLUC/3OHCOT compared to Whites. Age, liver function, alcoholic beverages, etc., were some of the other significant effects for some MRs. Menthol was not a statistically significant effect, e.g. the adjusted mean NNALGLUC/NNAL between menthol and non-menthol AS was 2.93 vs. 2.80 (p>0.05, AA) and 3.38 vs. 3.35 (p>0.05, Whites). The models only explained 2.6-12.6% of the MR variability. Number of cigarettes was the most important factor affecting serum cotinine levels. Conclusions: Menthol does not inhibit the metabolism of nicotine or NNK. The daily exposure of related constituents is primarily influenced by number of cigarettes smoked per day.
Drug metabolism letters. 11/2012;
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ABSTRACT: Androstenedione (4-androstene-3,17-dione) is banned by the World Anti-Doping Agency (WADA) as an endogenous steroid. The official method to confirm androstenedione abuse is isotope ratio mass spectrometry (IRMS). According to the guidance published by WADA, atypical steroid profiles are required to trigger IRMS analysis. However, in some situations, steroid profile parameters are not effective enough to suspect the misuse of endogenous steroids. The aim of this study was to investigate the atypical steroid profile induced by androstenedione administration and the detection of androstenedione doping using IRMS. Ingestion of androstenedione resulted in changes in urinary steroid profile, including increased concentrations of androsterone (An), etiocholanolone (Etio), 5α-androstane-3α,17β-diol (5α-diol), and 5β-androstane-3α,17β-diol (5β-diol) in all of the subjects. Nevertheless, the testosterone/epitestosterone (T/E) ratio was elevated only in some of the subjects. The rapid increases in the concentrations of An and Etio, as well as in T/E ratio for some subjects could provide indicators for initiating IRMS analysis only for a short time period, 2-22h post-administration. However, IRMS could provide positive determinations for up to 55h post-administration. This study demonstrated that, 5β-diol concentration or Etio/An ratio could be utilized as useful indicators for initiating IRMS analysis during 2-36h post-administration. Lastly, Etio, with slower clearance, could be more effectively used than An for the confirmation of androstenedione doping using IRMS.
Steroids 09/2011; 76(14):1560-5. · 2.83 Impact Factor
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ABSTRACT: Nicotine and its 5 major metabolites (Nicotine equivalents, NE) may serve as a surrogate biomarker for smoke exposure.
To investigate the relationship between nicotine equivalents (NE) and biomarkers of exposure (BOE) to cigarette smoke.
Data from nine controlled studies in 916 adult smokers were used. BOEs to nicotine, NNK, pyrene, acrolein, benzene, 1,3-butadiene and CO were used.
Among all the factors investigated (NE, cigarette type, age, gender, BMI and study), NE was the most statistically significant factor for all biomarker relationships. Weak to moderate relationships (0.32 ≤ R(2) ≤ 0.65) were found between NE and the BOEs.
Based on the relationships with BOEs, NE may be considered as a surrogate biomarker of total cigarette smoke exposure.
Biomarkers 03/2011; 16(2):144-54. · 2.21 Impact Factor
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ABSTRACT: It has been reported that adult smokers (AS) may be considering smokeless tobacco products as an alternative to smoking. The objective of this study was to evaluate the change in exposure in AS using Marlboro snus (MSNUS) (a tobacco pouch product in test market in June 2007).
AS were randomized into the following groups--CS: subjects (n = 30) continue smoking their own brand; DU: subjects (n = 60) reduced their daily cigarette consumption by >or=50% and were allowed to use MSNUS; SN: subjects (n = 15) stopped smoking their cigarettes but were allowed to use MSNUS; NT: subjects (n = 15) were not allowed to use any tobacco products for the entire duration of the 8-day study. Biomarkers of smoke exposure (BOE) measured at baseline and postbaseline were 24-hr urinary excretion of metabolites of N-nitrosamines, nicotine (urine and plasma), aromatic amines, benzene, and polycyclic aromatic hydrocarbon; urine mutagenicity; and carboxyhemoglobin at various timepoints.
Statistically significant (p < .05) reductions in all the urinary BOE were observed in the DU group compared with the CS group. After correcting for the residual effect, a proportionate reduction (approximately 50%) in most of the biomarkers was observed. Even larger reductions, similar to the NT group, were observed in the SN group.
The proportionate reduction in exposure when reducing the number of cigarettes by 50% and using MSNUS, under the consumption patterns observed, suggest that the AS did not appear to alter their smoking behavior. The added exposure from MSNUS usage in this group was minimal. The AS sustained substantial reductions in exposure when using MSNUS exclusively.
Nicotine & Tobacco Research 12/2009; 12(2):105-16. · 2.58 Impact Factor
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ABSTRACT: Measurement of endothelial function using peripheral arterial tonometry (PAT) has been reported to be significantly correlated with coronary blood flow. Repetitive PAT measurements were performed in 22 healthy male subjects at test intervals of 1 hour (5 times within a day) and 0.5 hours (7 times within a day) to evaluate the variability of the reactive hyperemia index (RHI). A total of 10 subjects underwent additional repetitive PAT at 2 hour intervals (7 times within a day) for 3 consecutive days to evaluate the diurnal effects and day-to-day reproducibility. The RHI from each test was computed automatically based on a 15 minute recording of pulse wave amplitude changes of the fingers in response to reactive hyperemia induced by a 5 minute occlusion of the brachial artery. Intrasubject variability of RHI at different test intervals, defined as the coefficient of variation (CV) was 15.3% +/- 5.3%, 16.1%+/- 7.8%, and 22.6% +/- 3.9% for the tests at 0.5 hour, 1 hour, and 2 hour intervals, respectively. Reactive hyperemia indices measured at the same time points on each of the 3 days were not statistically significant. The interday reproducibility, presented as intraclass correlation coefficients (ICC) ranged from - 0.07 to 0.47. We conclude that repetitive PAT measurements have no carryover effect on RHI at 1 hour, and 2 hour intervals, and the RHI measured at 0.5 hour intervals is associated with a trend of increase. The interday reproducibility is relatively low and the intrasubject variability of RHI is similar to those observed in studies of flow-mediated dilation using brachial artery ultrasound scanning.
Clinical Cardiology 12/2009; 32(12):700-4. · 2.15 Impact Factor
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ABSTRACT: Cigarette smoke is a complex aerosol that includes a gas vapor phase and a particulate phase. Inclusion of activated carbon in the cigarette filter can reduce some of the gas-phase smoke constituents implicated as toxicologically relevant. The present study evaluated exposure to selected gas-phase constituents when adult smokers switched to prototype cigarettes with a highly activated carbon filter. Smokers (N = 160) in two separate studies were randomized to continue to smoke conventional cigarettes (either a 6-mg or 11-mg FTC tar product), to smoke test cigarettes containing carbon filters (comparable tar levels), or to stop smoking. After completing 8 days in controlled smoking conditions (short-term studies), smokers had the option to continue in 24-week long-term ambulatory studies with unrestricted smoking. Urinary excretion of mercapturic acid metabolites of 1,3-butadiene, acrolein, and benzene; nicotine and five of its metabolites, total NNAL, and 1-hydroxypyrene were measured at baseline in the conventional cigarette group, in all groups in the short-term studies, and every 4 weeks in the long-term studies. In the short-term studies, statistically significant reductions (>70%, p<.001) in gas-phase biomarker levels were observed in the test cigarette group for both tar level products compared with the conventional cigarette group. These reductions were similar to those observed in the stop-smoking groups. The reductions continued consistently (p<.001) throughout the long-term studies. Switching to test cigarettes minimally affected the particulate-phase biomarkers. Statistically significant and consistent reductions in selected gas vapor phase biomarkers were observed when smokers switched to activated carbon filter cigarettes.
Nicotine & Tobacco Research 01/2009; 10(12):1761-72. · 2.58 Impact Factor
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ABSTRACT: Rationale. To date no state-of-the-art clinical study has been conducted to address the question as to whether switching to lower tar cigarettes reduces exposure to smoke constituents in humans. Methods. Randomized, controlled, forced switching study in 225 adult smokers of full flavor Marlboro (MFF) cigarettes for 8 days with a 24-week follow-up. Subjects smoked MFF (a 15-mg Federal Trade Commission (FTC) tar cigarette) at baseline and were randomized to smoke 11-mg Marlboro Lights (ML) or 6-mg Marlboro Ultra Lights (MUL) cigarettes. Biomarkers of exposure to nicotine, 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene, CO, benzene, acrolein, and mutagenic substances were measured. Results. In the short-term phase, switching from MFF to ML showed statistically significant decreases in nicotine exposure (-13%) and non-significant increases in CO exposure (+6%), while switching from MFF to MUL showed statistically significant decreases in nicotine (-27%) and CO (-13%) exposure. Both nicotine and CO biomarkers trended similarly in the 24-week follow-up as in the short-term phase. The other biomarkers of cigarette smoke constituents followed the same trend as nicotine at the end of the 24-week follow-up. Conclusions. Switching smokers to lower FTC tar yield cigarettes, on average, reduces nicotine and other biomarkers considered surrogates of tar exposure.
Regulatory Toxicology and Pharmacology 06/2008; 51(3):295-305. · 2.43 Impact Factor
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ABSTRACT: The analytical data for identifying an unknown substance that was found in a nutrition supplement is presented. The unknown substance is purified using thin-layer chromatography and then measured using high-resolution mass spectrometry (HRMS) giving the exact mass from which the structure of the unknown substance was proposed. The procedure for synthesizing N-nitrosofenfluramine from fenfluramine is described. The extracted, synthesized, and standard N-nitrosofenfluramine are compared using HRMS, high-performance liquid chromatography (HPLC)-MS, HPLC-UV, Fourier transform IR spectroscopy, gas chromatography-MS, TLC, and NMR (1H NMR and 13C NMR). All analytical data obtained confirm that the unknown peak in the nutrition supplement is N-nitrosofenfluramine and that the synthetic procedure described can easily provide the N-nitrosofenfluramine reference substance for identification.
Journal of chromatographic science 02/2005; 43(1):7-10. · 0.88 Impact Factor
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ABSTRACT: There is limited information comparing biomarkers of exposure (BOE) to cigarette smoke in menthol (MS) and non-menthol cigarette smokers (NMS). Objective: To compare BOE to nicotine and carbon monoxide in MS and NMS. Methods: Cross-sectional, observational, ambulatory, multi-centre study in 3341 adult cigarette smokers. Nicotine equivalents (NE) in 24 h urine, NE/cigarette, COHb and serum cotinine were measured. Statistical analyses included analysis of variance and Wilcoxon test. Results: Analyses of variance revealed no statistically significant effects of mentholated cigarettes on NE/24 h, COHb, serum cotinine and NE/cigarette. On average MS smoked 15.0 and NMS 16.8 cigarettes/day. The unadjusted mean differences were as follows: MS had lower NE/24 h (5.4%) and COHb (3.2%), higher serum cotinine (3.0%) and NE/cigarette (5.7%) than NMS. African-Americans MS smoked 40% fewer cigarettes, showed lower NE/24 h (24%) and COHb (10%) and higher NE/cig (29%) and serum cotinine (8%) levels than their White counterparts. Conclusions: Smoking mentholated cigarettes does not increase daily exposure to smoke constituents as measured by NE and COHb. These findings are consistent with the majority of epidemiological studies indicating no difference in smoking related risks between MS and NMS.
Regulatory Toxicology and Pharmacology.
