Differences In Urinary Concentrations Research Articles

Comparison of urine heavy metals in exclusive menthol and non-menthol cigarette users by race/ethnicity: The 2015-2016 National Health and Nutrition Examination Survey Special Sample.

The objective of this study was to investigate the differences in urine concentrations of heavy metals (uranium, cadmium, and lead) between exclusive menthol and non-menthol cigarette smokers across three racial/ethnic groups using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 Special Sample. Data from NHANES 2015-2016 Special Sample were analyzed to assess the association between menthol smoking and heavy metal biomarkers in urine across three racial/ethnic groups (N=351), including Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic/Other (HISPO). Multivariable linear regression models were used to estimate adjusted geometric means (GMs) and ratio of GMs (menthol/non-menthol smokers) (RGMs) for urine biomarkers of heavy metals between menthol and non-menthol smokers by race/ethnicity. Among the 351 eligible participants, 34.4% (n=121) were NHW, 33.6% (n=118) were NHB, and 32.0% (n=112) were HISPO exclusive cigarette smokers. The analysis revealed significantly higher concentrations of urine uranium in NHB menthol smokers compared to NHB non-menthol smokers (RGMs=1.3; 95% CI: 1.0-1.6; p=0.04). NHW menthol smokers appeared to have higher levels of urine uranium than non-menthol smokers, but the difference was not statistically significant (9.0 vs 6.3; RGMs=1.4; 95% CI: 1.0-2.2; p=0.08). There were no significant differences in urine metals (cadmium and lead) by menthol status among NHW, NHB, or HISPO cigarette smokers (p>0.05). The research findings regarding the higher levels of urine uranium among Non-Hispanic Black (NHB) menthol cigarette smokers raise questions about the claims suggesting that additives in cigarettes do not contribute to increased toxicity.

An assessment of exposure to several classes of pesticides in pet dogs and cats from New York, United States

Exposure of pet dogs and cats to pesticides used in and around homes (e.g., lawns and gardens) is a significant health concern. Furthermore, some pesticides are directly used on dogs and cats for flea, lice, and tick control. Despite this, little is known regarding the extent of pesticide exposure in pets. In this study, we determined the concentrations of 30 biomarkers of pesticide exposure in urine collected from dogs and cats in New York State, USA: 6 dialkylphosphate (DAP) metabolites of organophosphates (OPs); 14 neonicotinoids (neonics); 3 specific metabolites of OPs; 5 pyrethroids (PYRs); and 2 phenoxy acids (PAs). The sum median concentrations of these 30 pesticide biomarkers (ΣPesticides) in dog and cat urine were 35.2 and 38.1 ng/mL, respectively. Neonics were the most prevalent in dogs (accounting for 43% of the total concentrations), followed by DAPs (17%), PYRs (16%), OPs (13%), and PAs (∼10%). In cat urine, neonics alone accounted for 83% of the total concentrations. Elevated concentrations of imidacloprid were found in the urine of certain dogs (max: 115 ng/mL) and cats (max: 1090 ng/mL). Some pesticides showed gender- and sampling location- related differences in urinary concentrations. We calculated daily exposure doses of pesticides from the measured urinary concentrations through a reverse dosimetry approach. The estimated daily intakes (DIs) of chlorpyrifos, diazinon, and cypermethrin were above the chronic reference doses (cRfDs) in 22, 76, and 5%, respectively, of dogs. The DIs of chlorpyrifos, parathion, diazinon, and imidacloprid were above the cRfDs in 33, 14, 100, and 29%, respectively, of cats. This study thus provides evidence that pet dogs and cats are exposed to certain pesticides at levels that warrant immediate attention.

Occupational differences in personal care product use and urinary concentration of endocrine disrupting chemicals by gender.

In most societies, women and men systematically differ in consumption of cosmetics and household products, which are interlinked with gendered norms and occupational segregation. We investigated the differences in personal care product (PCP) use and exposure to endocrine disrupting chemicals (EDCs) based on occupation and gender. We utilized data from the first to third Korean National Environmental Health Survey analyzing 9218 participants aged 20-59 years engaged in their current occupation for ≥3 months. Frequent PCP use (≥once/week) and exposure to EDCs were analyzed by gender and occupation. We used least-square geometric means (LSGMs) of urinary concentrations of the five EDCs adjusted for covariates. Manual occupation was most common in men and no paid occupation was most frequent in women. In general, clerical, service, and sales workers showed the highest prevalence of frequent use of hair and body products. Women used body and makeup products more frequently than men. For all five EDCs, similarly, women showed higher urinary levels in all occupation groups. When stratified by gender, the differences in urinary concentration of EDCs across occupation groups were not observed in men. Among women, clerical, service, and sales workers showed higher bisphenol A (BPA) and mono-n-butyl phthalate (MnBP) levels than manual workers. Differentials in exposure to EDCs by occupation groups were not evident for men. Given the higher urinary concentration of EDCs in women compared to men, interventions to reduce the exposure to EDCs would need to focus on women, especially in clerical, service, and sales occupations.

Comparison of urine fibrinogen and interleukin-6 concentrations between healthy dogs and dogs with risk factors for enterococcal bacteriuria.

To compare urine concentrations of fibrinogen (uFIB) and interleukin-6 (uIL-6) between dogs with risk factors for enterococcal bacteriuria and healthy dogs. Banked urine samples with negative aerobic culture results from 8 dogs with urolithiasis, 9 dogs with anatomic abnormalities of the lower portion of the urinary tract (LUT), 10 dogs with LUT neoplasia, and 21 healthy control dogs. Urine creatinine concentration (uCrea) was determined by an automated biochemical analyzer, and uFIB and uIL-6 were determined by dog-specific ELISAs. The uFIB:uCrea and uIL-6:uCrea ratios were calculated for each sample to normalize intersample differences in urine concentration and were compared among the 4 experimental groups. Median uFIB:uCrea ratios for dogs with urolithiasis (0.72; interquartile [25th to 75 percentile] range [IQR], 0.46 to 3.48) and LUT neoplasia (6.16; IQR, 3.89 to 12.75), but not for dogs with LUT anatomic abnormalities (0.48; IQR, 0.27 to 0.69), were significantly greater than that for control dogs (0.17; IQR, 0.07 to 0.39). Median uIL-6: uCrea ratios for dogs with urolithiasis (0.48; IQR, 0.18 to 1.61), LUT anatomic abnormalities (0.25; IQR, 0.17 to 0.33), and LUT neoplasia (0.25; IQR, 0.12 to 1.01) were significantly greater than that for control dogs (0.08; IQR, 0.06 to 0.11). The uFIB and uIL-6 in dogs with risk factors for enterococcal bacteriuria were generally greater than corresponding values in control dogs. Further investigation is necessary to determine the role of fibrinogen in enterococcal colonization of the urinary tract of dogs.

Association between urinary polycyclic aromatic hydrocarbons and hypertension in the Korean population: data from the Second Korean National Environmental Health Survey (2012\u20132014)

Polycyclic aromatic hydrocarbons (PAHs) are environmental and occupational pollutants derived from incomplete combustion of organic materials, including wood and fossil fuels. Epidemiological studies have evaluated the association between PAH exposure and hypertension or cardiovascular disease in the general population, but the evidence is limited. In this study, we evaluated the association between urinary PAH metabolites and hypertension in the Korean adult population. A total of 6478 adults who participated in the Second Korean National Environmental Health Survey (2012–2014) were included. The differences in urinary concentrations of four PAH metabolites, including 1-hydroxypyrene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 2-naphthol, were compared according to hypertension status using a general linear model. Adjusted odds ratios (aORs) for hypertension were calculated according to the quartile groups of urinary PAH metabolites after adjusting for age, sex, body mass index (BMI), smoking, and alcohol consumption in multiple logistic regression analyses. The estimated mean concentrations of urinary 1-hydroxyphenanthrene were significantly higher in the hypertension group than in the non-hypertension group. In 1-hydroxyphenanthrene, the OR for hypertension was significantly higher in the third and fourth quartile groups than in the first quartile group (third: OR 1.707, 95% CI 1.203–2.423, fourth: OR 1.604, 95% CI 1.158–2.223). No significant associations were detected for the other metabolites. Our results suggest an association between exposure to PAHs and hypertension in a Korean adult population. Further studies are required to evaluate the effects of low-dose long-term exposure to PAHs on hypertension and cardiovascular disease.

Occurrence of parabens and their metabolites in the paired urine and blood samples from Chinese university students: Implications on human exposure

Parabens, a group of p-hydroxybenzoic acid esters, are extensively used in cosmetics, personal care products, pharmaceuticals, and foodstuff. In the present study, the total forms (free plus conjugated) of four parent parabens, such as methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), and four metabolites, namely methyl protocatechuate (OH–MeP), ethyl protocatechuate (OH–EtP), p-hydroxy benzoic acid (4-HB), and 3,4-dihydroxy benzoic acid (3,4-DHB), were detected in paired urine and blood samples collected from 196 Chinese university students. The median urinary and blood parabens and their metabolites concentrations ranged from 0.24 to 167 ng/mL and from <0.02 to 2.88 ng/mL, respectively. MeP was the predominant parent parabens, accounting for 68% and 52% of urine and blood samples, respectively. Furthermore, 4-HB predominantly contributed to the parabens and their metabolites in urine (54%) and blood (41%). Significant positive correlations were observed between the urinary levels and blood levels. Moreover, relatively high levels of parabens and their metabolites were detected in urine samples. Our results imply that urinary concentrations are good predictors of human exposure to parabens and metabolites. Gender-related difference in urinary concentrations of parabens and their metabolites were found. The median urinary levels of the tested compounds in females were significantly higher than those in males (Mann Whitney U test, p < 0.05 or 0.01). The estimated daily intakes (EDIs) of MeP, EtP, and PrP were also evaluated. The median values of EDIMeP, EDIEtP, and EDIPrP for all of the university students were estimated to be 25.9, 1.61, and 3.82 μg/kg bw/day, respectively. The median values (μg/kg bw/day) of EDIMeP, EDIEtP, and EDIPrP were higher in females (53.7, 8.65, and 5.22) than in males (8.41, 0.85, and 2.57). This study is the first study to report the occurrence of parabens and their metabolites in paired urine and blood samples in China.

Mothers and children are related, even in exposure to chemicals present in common consumer products

BackgroundPhthalates, bisphenol A (BPA) and triclosan (TCS) are detectable in the vast majority of people. Most humans are continuously exposed to these chemicals due to their presence in food or in everyday consumer products. The measurement of these compounds in family members may help to explore the impact of major lifestyle factors on exposure. Mothers and (young) children are especially interesting to study, as they mostly share considerable parts of daily life together. Materials and methodsPhthalate metabolites, bisphenol A (BPA) and triclosan (TCS) were measured in first morning void urine, collected in mother-child pairs (n = 129) on the same day. The mothers (27-45y) and their children (6-11y) were recruited in the Brussels agglomeration and rural areas of Belgium in the context of the European COPHES-DEMOCOPHES human biomonitoring project. Face-to-face questionnaires gathered information on major exposure sources and lifestyle factors. Exposure determinants were assessed by multiple linear regression analysis. ResultsThe investigated compounds were detectable in nearly all mothers (92.8–100%) and all children (95.2–100%). The range (P90 vs. P10) of differences in urinary concentrations within each age group was for most compounds around 10–20 fold, and was very high for TCS up to 35 and 350-fold in children and mothers respectively. Some participants exceeded the tolerable daily intake guidelines as far as they were available from the European Food Safety Authority (EFSA). Overall, for BPA, the urinary concentrations were similar among both age groups. Most urinary phthalate metabolites were higher in children compared to the mothers, except for monoethyl phthalate (MEP). TCS levels were generally higher in the mothers. Despite the difference in mothers' and children's urinary concentrations, the creatinine-corrected levels were correlated for all biomarkers (Spearman rank r = 0.32 to 0.66, p < 0.001). Furthermore, for phthalates, similar home and lifestyle factors were associated with the urinary concentrations in both age groups: home renovation during last two years or redecoration during the last year for di-ethyl phthalate (DEP); PVC in home for di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP) and butyl benzyl phthalate (BBzP), and personal care products use for DiBP and DnBP. Based on questionnaire information on general food type consumption patterns, the exposure variability could not be explained. However, comparing the phthalate intake from the current study with earlier assessed Belgian food intake calculations for both ages, food in general was estimated to be the major intake source for di-ethyl hexyl phthalate (DEHP), with diminishing importance for BBzP, DiBP and DnBP. ConclusionOur results confirm, that children and their mothers, sharing diets and home environments, also share exposure in common consumer products related chemicals. By collecting morning urine levels on the same day, and using basic questionnaires, suspected exposure routes could be unraveled.

Early Life Exposure to Phthalates in CHILD: A Multi-City Canadian Birth Cohort

Phthalates, used as plasticizers and solvents, are ubiquitous in the environment. Phthalate exposure has been associated with adverse health effects including childhood asthma and allergic disease. Few studies have examined exposure to phthalates during early life particularly in infancy, a critical window for development. The Canadian Healthy Infant Longitudinal Development (CHILD) Study, a population-based birth cohort, has examined multiple environmental exposures during early life. The goal of this study was to characterize exposure to phthalates during infancy and early childhood in representative participants in the CHILD Study.Pregnant mothers were enrolled 2009-2012 across 4 cities and 1 rural area in Canada. Urine samples were collected at 3, 12 and 36 months of age and, in the first 1,578 children, analyzed for eight phthalate metabolites. Questionnaires were administered at each time point documenting the home environment and maternal and infant behaviours. Geometric mean (GM) metabolite concentrations were calculated at each age. Trends with age and factors that may influence urinary phthalate concentrations were examined using mixed models. Variability between all three measurements were assessed using intraclass correlation coefficients (ICC).Results indicated widespread exposure to phthalates. The highest urinary concentration was for the metabolite MBP at all time points (GM: 15-32 ng/mL). Concentrations of all phthalate metabolites significantly increased with age from 3 to 36 months. Low ICCs were observed for all metabolites (0 to 0.2), suggesting a high degree of variability between measurements from the same child at different ages. There were differences in urinary concentrations of MEP, MBP, MBzP, MCPP depending on study site and urinary MBzP concentrations decreased with mother's age. These data, which will be explored in detail in this presentation, describe widespread exposure to phthalates across a representative sample of the CHILD Study.

Distribution and predictors of urinary concentrations of phthalate metabolites and phenols among pregnant women in the Healthy Start Study

BackgroundPhthalates and phenols are suspected endocrine disrupting chemicals that may adversely impact fetal outcomes following in utero exposure. Understanding predictors of exposure to phthalates and phenols during the prenatal period is important. MethodsWe measured urinary concentrations of 15 phthalate metabolites and 11 phenols in 446 pregnant women enrolled in the Healthy Start pre-birth cohort. Creatinine-adjusted geometric means (GM) for each urinary biomarker were compared across categories of potential sociodemographic and dietary predictors. To assess the independent relationship between each significant food group predictor and biomarker we used multivariable models, adjusted for sociodemographic predictors. ResultsThe phthalate metabolites with the highest concentrations were monoethyl phthalate (GM: 41.1µg/g creatinine) and monocarboxyisooctyl phthalate (GM: 20.5µg/g creatinine). Benzophenone-3 (GM: 124.6µg/g creatinine) and methyl paraben (GM: 119.9µg/g creatinine) were the phenols with the highest concentrations. Concentrations of the metabolites of di-n-butyl phthalate and di(2-ethylhexyl) phthalate were significantly higher in younger, unmarried or unemployed mothers, those who were overweight or obese, those with lower educational attainment, or those of minority race/ethnicity (p-values < 0.05). Metabolites of di-n-butyl phthalate concentrations were 18% lower in those who consumed milk ≥ 7 times per week (95% CI: 30–4%). Benzophenone-3 and triclosan concentrations were significantly higher in older, married, or employed mothers, those with normal body mass index, higher educational attainment, higher household income, or who were non-Hispanic white (p-values < 0.05). Benzophenone-3 concentrations were 62% higher in those who consumed seafood ≥ 5 times per month (95% CI: 16–127%). ConclusionsWe observed differences in urinary concentrations of phthalates and phenol biomarkers by sociodemographic predictors in an ethnically diverse cohort of pregnant women. These results and future analyses from this prospective cohort will help inform targeted interventions to reduce exposure to these potential endocrine disrupting chemicals during pregnancy.

Sex and site differences in urinary excretion of conjugated pyrene metabolites in the West African Shorthorn cattle.

Industrialization, economic and population growth rates in Ghana have increased the release of contaminants including polycyclic aromatic hydrocarbons (PAHs) into the environment through which humans and animals are exposed. Cattle is reported to be exposed to high levels of PAHs through feed and inhalation. Once exposed, PAHs are metabolized and excreted in urine, feces or bile. In a previous study, cattle in Ghana was reported to excrete high levels of 1-hydroxypyrene (1-OHPyr) due to high exposure to the parent compound, pyrene. 1-OHPyr is further metabolized to glucuronide and sulfate conjugates. Thus, the aim of this study was to investigate the sex and site differences in urinary excretion of conjugated pyrene metabolites using cattle urine collected from rural and urban sites of the Ashanti region, Ghana. From the results, geometric mean concentration adjusted by specific gravity indicated that 1-OHPyreneGlucuronide (PyG) was the most abundant conjugate followed by PyrenediolSulfate (M3). The sum of conjugated pyrene metabolites and sum of both conjugated and deconjugated pyrene metabolites correlated significantly with PyG, PydiolSulfate (M2) and PydiolSulfate (M3). The study revealed no significant difference in urinary excretion of conjugated pyrene metabolites between rural and urban sites. This indicated that similar to urban sites, cattle in rural sites were exposed to high levels of pyrene. There was no significant difference in urinary concentrations of conjugated pyrene metabolites between sexes.

PD65-05 URINE EXPRESSION OF TIMP1, SERPINB1, AND SEMENOGELIN 2 MAY DIFFERENTIATE MEN WITH LOW-RISK OR NO EVIDENCE OF PROSTATE CANCER FROM MEN WITH HIGH-RISK OR METASTATIC DISEASE

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2017PD65-05 URINE EXPRESSION OF TIMP1, SERPINB1, AND SEMENOGELIN 2 MAY DIFFERENTIATE MEN WITH LOW-RISK OR NO EVIDENCE OF PROSTATE CANCER FROM MEN WITH HIGH-RISK OR METASTATIC DISEASE Sarah Prophet, Adam Feldman, Mary Fergus, and Bruce Zetter Sarah ProphetSarah Prophet More articles by this author , Adam FeldmanAdam Feldman More articles by this author , Mary FergusMary Fergus More articles by this author , and Bruce ZetterBruce Zetter More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2955AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES While serum PSA and other available diagnostic biomarkers can provide valuable guidance for assessing the risk of prostate cancer (PCa), limitations in accuracy persist. Novel biomarkers with improved performance characteristics are needed. Using mass spectrometry-based proteomics, we have identified three urinary proteins with significantly different expression patterns across PCa stages. This study evaluates the expression of these potential biomarkers in urine. METHODS Urinary protein concentrations of three proteins, TIMP1, serpinB1, and semenogelin 2, were assessed via Western blot and ELISA for 160 total urine samples. Each patient group (control, Gleason 6 PCa, Gleason ≥8 PCa, and metastatic PCa) had 40 samples. Urine protein was isolated using Amicon Ultra-15 Centrifugal Filter Units for Western blotting. ELISAs were performed using untreated raw urine samples. Immunohistochemistry (IHC) was performed on prostate tissue sections for all three proteins of interest. RESULTS TIMP1 levels were statistically higher in control and Gleason 6 PCa urine samples than for Gleason ≥8 and metastatic disease (2.19 ± 1.7 vs. 1.23 ± 1.13 ng/mL; p = 0.002). Expression of serpinB1 was significantly higher in men with Gleason 6 PCa than those with high-grade Gleason ≥8 PCa (0.71 ± 0.49 vs. 0.23 ± 0.33 ng/mL; p = 0.003). Metastatic PCa had significantly higher semenogelin2 concentrations in urine than healthy men (155.68 ± 74.3 vs. 81.55 ± 55.6 pg/mL; p = 0.02), and expression levels seem to rise with disease progression. IHC staining of tissue sections corroborated these findings. CONCLUSIONS Our results indicate differences in urinary concentrations of TIMP1, serpinB1, and semenogelin 2 across PCa stages. These novel biomarkers allowed distinction between men without prostate cancer or low-risk disease and those with high-risk or metastatic disease. These proteins represent potentially valuable non-invasive prostate cancer biomarkers and warrant further investigation. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1268 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Sarah Prophet More articles by this author Adam Feldman More articles by this author Mary Fergus More articles by this author Bruce Zetter More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Life without plastic: A family experiment and biomonitoring study

Exposure to bisphenol-A (BPA) and phthalates has been associated with negative health outcomes in animal and human studies, and human bio-monitoring studies demonstrate widespread exposure in the US and Europe. Out of concern for the environment and health, individuals may attempt to modify their environment, diet, and consumer choices to avoid such exposures, but these natural experiments are rarely if ever quantitatively evaluated.The aim of the study was to evaluate the difference in urinary concentrations of BPA and phthalate metabolites following an exposure reduction intervention among an Austrian family of five.Urine samples were taken shortly after the family had removed all plastic kitchenware, toys, and bathroom products, and started a concerted effort to eat less food packaged in plastic. Two-months later, urine samples were collected at a follow-up visit, and concentrations of BPA and phthalate metabolites were compared.Shortly after removal of plastic urinary concentrations of BPA were below limit of quantification in all samples. Phthalate concentrations were low, however, 10 of 14 investigated metabolites could be found above limit of quantification. After the two-month intervention, phthalate urinary concentrations had declined in some but not all family members. In the mother most phthalate metabolites increased.The low levels might be partly due to the environmentally conscious lifestyle of the family and partly due to the fact that body levels had dropped already because of the delay of four days between finishing removal and first measurement. Further two months avoidance of dietary exposure and exposure to environmental plastics reduced urinary concentrations for all but one metabolite in the oldest son only, but decreased somewhat in all family members except the mother.

Urinary Metabolites of Polycyclic Aromatic Hydrocarbons and the Association with Lipid Peroxidation: A Biomarker-Based Study between Los Angeles and Beijing.

Air pollution is among the top threats to human health in China. As air toxicants, polycyclic aromatic hydrocarbons (PAHs) could bring significant risks to population; however, the exposure to PAHs in China and its health impact are not fully understood. In 2012, a summer exchange program allowed 10 students to travel from Los Angeles to Beijing and stay there for 10 weeks. Based on the program, this study investigated the difference in urinary concentration of 12 hydroxylated-PAHs (Σ12OH-PAHs) and malondialdehyde (MDA) between the two cities. The median concentration of Σ12OH-PAHs in Beijing (14.1 μg g(-1) creatinine) was significantly higher than that in Los Angeles (5.78 μg g(-1) creatinine), indicating a higher exposure in Beijing. The ratios of homogeneous OH-PAHs (e.g., 1-/2-OH-NAP) changed significantly between the two cities (p < 0.01), which might suggest a potential alteration in metabolism subsequent to exposure. A significant association between Σ12OH-PAHs and MDA (p < 0.01) was observed, with the association varying between the two cities. This study suggests that exposure to PAHs might be linked to metabolism alteration and calls for future studies to investigate the role this possible alteration played in the health effects of PAHs exposure.

Effects of Paraoxonase 1 gene polymorphisms on organophosphate insecticide metabolism in Japanese pest control workers.

Paraoxonase 1 (PON1) in serum detoxifies organophosphate (OP) insecticides by hydrolysis. The present cross-sectional study aimed to clarify the relationship between PON1 single nucleotide polymorphisms (SNPs) and enzyme activities or OP metabolite concentrations in urine of workers occupationally exposed to low-level OPs. Among 283 workers in 10 pest control companies located in central Japan who underwent checkups, 230 subjects (male 199, female 31, average age 38.9 ± 11.1 years old) participated in the study. Q192R and L55M polymorphisms were determined by TaqMan assay. PON1 activity was measured using fenitrothion (FNT) oxon, chlorpyrifos-methyl (CPM) oxon, chlorpyrifos (CP) oxon, and phenyl acetate as substrates. Urinary OP metabolite concentrations were measured with gas chromatography-mass spectrometry. The maximum differences in enzyme activities between individuals were 64.6-, 6.3-, 7.7-, and 2.0-fold for FNT oxonase, CPM oxonase, CP oxonase, and arylesterase (ARE), respectively. The activities of CPM oxonase and ARE in workers having the RR genotype were 53.5% and 18.2% lower than in those with the QQ genotype, respectively. CP oxonase activity was 15.0% lower in those having the M allele (LM + MM compared with LL). Urinary metabolite concentrations were not associated with PON1 polymorphisms, but negative associations were observed between the concentrations and activities of FNT oxonase and ARE. While PON1 SNPs can explain differences in catalytic activities toward some OPs, differences in urinary concentrations of OP metabolites are not attributable to PON1 SNPs but instead are attributable to its serum activities. Its serum activities might be more sensitive biomarkers for estimation of individual susceptibility to OP toxicities.

Levels of Phthalate Metabolites in Urine of Pregnant Women and Risk of Clinical Pregnancy Loss.

Toxicological studies have shown that phthalate esters (PAEs), a class of widely used and environmentally prevalent chemicals, can increase the abortion rate in animals, but epidemiological evidence is scarce. This study aimed to explore the relationship between the urinary concentration of phthalate metabolites and the risk of clinical pregnancy loss. A total of 132 women who underwent clinical pregnancy loss (cases) and 172 healthy pregnant women (controls) were recruited from Beijing, China. Eight phthalate metabolites in urine were determined by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono(2-ethlyhexyl) phthalate (MEHP), were detected in at least 95% of the urine samples, with the highest median concentration of 51.0 μg/g of creatinine for MnBP of all participants. The differences in urinary concentrations of phthalate metabolites between cases and controls were evaluated using the Mann-Whitney U test. The concentrations of MEP (median of 18.7 μg/g of creatinine), MiBP (23.3 μg/g of creatinine), and MnBP (58.2 μg/g of creatinine) detected in the cases were significantly higher than those (15.7 μg/g of creatinine for MEP, 19.4 μg/g of creatinine for MiBP, and 43.9 μg/g of creatinine for MnBP) in the controls (p < 0.05). Increasing risks of clinical pregnancy loss were observed from the first to fourth quartiles of the MEP, MiBP, and MnBP concentrations (p < 0.05 for trend). We concluded that exposure to MEP, MiBP, and MnBP was associated with an increased risk of clinical pregnancy loss.

Sex differences in the relation between 24h urine volume and osmolality (LB710)

Twenty‐four hour (24h) urinary hydration biomarkers have value in assessing hydration and disease risk. Specifically, highly concentrated urine and low urine volume increase relative risk for lithiasis and chronic kidney disease, respectively, and thus maintaining a high volume of dilute urine has been suggested as a simple preventive measure. Although there is a strong inverse relationship between 24h urine osmolality (UOsm) and volume (UVol), sex differences in urine concentration have been reported. This suggests the possibility of sex differences in the UOsm:UVol relationship which have not been fully explored. Our aim was to assess sex differences in the relationship between UOsm and UVol, and to determine whether body mass may explain any observed differences. METHODS: 24h urine samples from 238 healthy American and French adults (50% men; age 28±6 y; BMI 22.9 ± 2.6 kg∙m‐2) were analyzed for UOsm and UVol. Sex differences in the UVol:UOsm relationship were evaluated with linear regression. RESULTS: UOsm was higher in men at any given UVol (whole model R2=0.67; βwomen mean±SE; ‐127±11 mOsm∙kg‐1; p&lt;.0001); however, the change in UOsm for a given change in UVol was not different between sexes. Adjusting for body mass reduced the UOsm gap between men and women (βwomen; ‐95±13 mOsm∙kg‐1), yet sex remained as a significant predictor of UOsm and the fit of the model was unchanged (whole model R2=0.68; p&lt;.0001). Although the distributions of both UOsm and UVol show a slight positive skew; neither log‐ nor root‐ transformations substantially improved the fit of the model, nor the UOsm gap between men and women. CONCLUSIONS: At similar UVol, men have higher UOsm than women. Though differences in body mass explain part of this sex gap, other factors likely play a role in the differential relationship of UVol:UOsm in men and women.

(115) Interpretation of urine drug testing results in patients using transdermal buprenorphine preparations for the treatment of chronic non-cancer pain

The use of buprenorphine for the management of chronic pain has risen rapidly since the FDA approved a transdermal formulation of this opioid in 2010. Consensus guidelines for the use of chronic opioid therapy highlight the importance of routine monitoring for patience compliance using periodic urine drug screens. The validity of the urine buprenorphine detection assay, currently in widespread use, was established for monitoring patient compliance in patients receiving sublingual formulations (e.g. subutex, suboxone) in the outpatient addiction treatment setting. However, transdermal dosing is an order of magnitude lower (mcg range) than sublingual (mg range). This retrospective analysis of tandem LC-MS urine samples from a single reference laboratory compares the results from two different buprenorphine treatment cohorts: transdermal pain treatment and sublingual detoxification. Samples from the group (n=54) undergoing pain treatment with the transdermal formulation showed urine concentrations of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine glucuronide significantly lower than the range of those treated with sublingual preparations (often below the 5mcg/ml limit of detection). The analyte that differed the most between the two patient groups was norbuprenorphine, detected in only 16.2% of transdermal patients with an overall median concentration of < 3 ng/mL, versus 100% of sublingual patients with a median concentration of 88 ng/mL. Buprenorphine-glucuronide demonstrated the highest positive rate of detection at 97.3% in samples from the transdermal group with at least one positive detectable analyte. This study demonstrates that urine parent drug and metabolite profiles are markedly different for the distinct patient populations using sublingual and transdermal buprenorphine formulations. Failure to recognize the difference in urine concentrations may lead to a misinterpretation of noncompliance. Assays with high sensitivity for buprenorphine glucuronide will likely have greater relevance in the pain treatment setting. The use of buprenorphine for the management of chronic pain has risen rapidly since the FDA approved a transdermal formulation of this opioid in 2010. Consensus guidelines for the use of chronic opioid therapy highlight the importance of routine monitoring for patience compliance using periodic urine drug screens. The validity of the urine buprenorphine detection assay, currently in widespread use, was established for monitoring patient compliance in patients receiving sublingual formulations (e.g. subutex, suboxone) in the outpatient addiction treatment setting. However, transdermal dosing is an order of magnitude lower (mcg range) than sublingual (mg range). This retrospective analysis of tandem LC-MS urine samples from a single reference laboratory compares the results from two different buprenorphine treatment cohorts: transdermal pain treatment and sublingual detoxification. Samples from the group (n=54) undergoing pain treatment with the transdermal formulation showed urine concentrations of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine glucuronide significantly lower than the range of those treated with sublingual preparations (often below the 5mcg/ml limit of detection). The analyte that differed the most between the two patient groups was norbuprenorphine, detected in only 16.2% of transdermal patients with an overall median concentration of < 3 ng/mL, versus 100% of sublingual patients with a median concentration of 88 ng/mL. Buprenorphine-glucuronide demonstrated the highest positive rate of detection at 97.3% in samples from the transdermal group with at least one positive detectable analyte. This study demonstrates that urine parent drug and metabolite profiles are markedly different for the distinct patient populations using sublingual and transdermal buprenorphine formulations. Failure to recognize the difference in urine concentrations may lead to a misinterpretation of noncompliance. Assays with high sensitivity for buprenorphine glucuronide will likely have greater relevance in the pain treatment setting.

Combination of Injection Volume Calibration by Creatinine and MS Signals’ Normalization to Overcome Urine Variability in LC-MS-Based Metabolomics Studies

It is essential to choose one preprocessing method for liquid chromatography-mass spectrometry (LC-MS)-based metabolomics studies of urine samples in order to overcome their variability. However, the commonly used normalization methods do not substantially reduce the high variabilities arising from differences in urine concentration, especially for signal saturation (abundant metabolites exceed the dynamic range of the instrumentation) or missing values. Herein, a simple preacquisition strategy based on differential injection volumes calibrated by creatinine (to reduce the concentration differences between the samples), combined with normalization to "total useful MS signals" or "all MS signals", is proposed to overcome urine variabilities. This strategy was first systematically compared with other popular normalization methods by application to serially diluted urine samples. Then, the method has been verified using rat urine samples of pre- and postinoculation of Walker 256 carcinoma cells. The results showed that the calibration of injection volumes based on creatinine values could effectively eliminate intragroup differences caused by variations in the concentrations of urinary metabolites, thus giving better parallelism and clustering effects. In addition, peak area normalization could further eliminate intraclass differences. Therefore, the strategy of combining peak area normalization with calibration of injection volumes of urine samples based on their creatinine values is effective for solving problems associated with urinary metabolomics.

Metabonomic investigations of age- and batch-related variations in female NMRI mice using proton nuclear magnetic resonance spectroscopy

The NMRI outbred mouse model is widely used for studying metabolic disease, toxicity, and infection, yet information regarding baseline metabolism of this murine strain is relatively sparse. Using different batches of female NMRI mice, we assessed the stability of the metabolic phenotype with increasing age and weight, and determined the influence of acclimatization on the metabolic profile of biofluids (urine, plasma, and faecal water). Differences in urinary concentrations of 3-ureidopropionate, 2-oxoisocaproate, trimethylamine, and glycine were detected between three batches of 9-week-old female NMRI mice using proton nuclear magnetic resonance ((1)H NMR) spectroscopy coupled with multivariate statistical analysis. An acclimatization period of 2 weeks was imposed after the mice entered the laboratory environment. Strong differences in the faecal metabolome pre- and post-acclimatization were found (reduction in amino acid concentrations), whilst the urine metabolome showed increased levels of trimethylamine-N-oxide, phenylacetyl glycine, and hippurate with decreased excretion of formate and betaine post-acclimatization. Temporal variation in the metabolite profiles over a 16-week study stabilized around 7-week-old animals. The results from this study strongly argue for inclusion of an acclimatization period prior to starting an investigative procedure, and suggest that the metabolic phenotypes of female NMRI mice are more stable at around 7 weeks of age. We have also identified a set of metabolites that are more susceptible to variation in concentration. This information can serve as a benchmark in order to establish confidence in systematic variation attributable to pathology or therapeutic intervention above the background metabolic variation in the NMRI mouse.

The Use of Biomarkers for Assessing HAART-Associated Renal Toxicity in HIV-Infected Patients

Renal toxicity has become an important issue in HIV-infected patients receiving highly active antiretroviral therapy (HAART). Several biomarkers are available for monitoring renal function, although no consensus exists on how best to apply these tools in HIV infection. The best biomarker is the glomerular filtration rate (GFR), and several creatinine-based estimates equations of GFR are widely used in HIV infection, with clinical advantages for the equation developed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Although serum cystatin C has been proposed as a more sensitive marker of renal dysfunction in HIV infection, it may be affected by ongoing inflammation. Tubular dysfunction can be simple or complex, depending on whether the tubular transport of one or more substances is affected. Multiple renal tubular dysfunction or Fanconi syndrome is characterized by alterations in the reabsorption of glucose, amino acids, phosphate and often also bicarbonate. Therefore, Fanconi syndrome would be the tip of the iceberg, and the most unusual and severe manifestation. In the last years, several low molecular weight proteins as markers of tubular alteration, including retinol-binding protein, b2-microglobulin, and neutrophil gelatinase associated lipocalin have become available. Different studies have shown differences in urine concentrations of these proteins in patients receiving tenofovir, but again, no consistent data have shown their clinical usefulness in predicting the clinical consequences of tubular alteration. Thus, we review findings from recent studies performed in this area to describe the performance of new biomarkers for renal damage in HIV-infected patients.