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1.
Arch Toxicol ; 93(10): 2913-2926, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31511936

RESUMO

Occupational exposure limits (OELs) are derived for protection from health hazards, assuming that exposed subjects are healthy adult workers. Whether differences in susceptibility to sensory irritation effects from airborne chemicals have to be taken into account is currently under discussion. Thus, we chose atopics as a healthy but possibly susceptible subpopulation that can be identified with a clinical test. To investigate the influence of sex or atopy on sensitivity to airborne chemicals, 22 subjects were exposed for 4 h to ethyl acrylate at three concentrations: 0.05 ppm (odor threshold; sham), 5 ppm (constant), and varying exposure between 0 and 10 ppm. Odor intensity decreased and eye irritation ratings increased in a dose-dependent manner, reflecting the time course of the exposure scenarios. The reports of moderate-to-strong eye irritation were verified by significant increases in eye blink frequency. Our results show that women reported subjective eye irritation to an increasing degree. However, these sex-related differences in ratings could not be verified by objective assessment of eye blink frequency. Atopic subjects reported higher odor intensity than non-atopic subjects, but only during the sham (odorous but not irritating) exposure condition. Differences in ratings on annoyance, and eye or nose irritation were not found. Furthermore, the study revealed that atopic subjects might belong to a group of subjects with frequent eye blink activity. Although the relative increase in blink rates was more pronounced in non-atopic subjects, atopic subjects had significant higher blink rates at the end of the exposure to varying ethyl acrylate concentrations. Our results do not support that atopy enhances chemosensory effects if only the increase of blink rates and not the absolute height are considered as adverse effect. Nevertheless, the results indicate that individuals with frequent eye blink activity should be distinguished from those with normal eye blink activity while investigating blink rates as objective parameter of eye irritation.

2.
Am J Epidemiol ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31504103

RESUMO

To investigate lung cancer risk of welding fumes, hexavalent chromium (Cr(VI)), and nickel (Ni), we analyzed 3,418 male lung cancer cases and 3,488 controls from two German case-control studies (1988-1996). We developed a welding-process exposure-matrix from measurements of these agents, which was linked with welding histories from a job-specific questionnaire to calculate cumulative exposure variables. Logistic regression models were fitted to estimate odds ratios with confidence intervals (CI) conditional on study and adjusted for age, smoking, and working in other at-risk occupations. Additionally, we mutually adjusted for the other exposure variables under study. Overall, 800 cases and 645 controls ever worked as regular or occasional welder. Odds ratios between lung cancer and high exposure were 1.55 (95% CI: 1.17, 2.05; median, 1.8 mg/m3 years) for welding fumes, 1.85 (95% CI: 1.35, 2.54; median, 1.4 µg/m3 years) for Cr(VI), and 1.60 (95% CI: 1.21, 2.12; median, 9 µg/m3 years) for Ni. Risk estimates increased with increasing cumulative exposure to welding fumes and with increasing exposure duration to Cr(VI) and to Ni. Our results showed that welding fumes, Cr(VI), and Ni may contribute independently to the excess lung cancer risk associated with welding. However, quantitative exposure assessment remains challenging.

3.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514337

RESUMO

Here, we discovered TGFBI as a new urinary biomarker for muscle invasive and high-grade urothelial carcinoma (UC). After biomarker identification using antibody arrays, results were verified in urine samples from a study population consisting of 303 patients with UC, and 128 urological and 58 population controls. The analyses of possible modifying factors (age, sex, smoking status, urinary leukocytes and erythrocytes, and history of UC) were calculated by multiple logistic regression. Additionally, we performed knockdown experiments with TGFBI siRNA in bladder cancer cells and investigated the effects on proliferation and migration by wound closure assays and BrdU cell cycle analysis. TGFBI concentrations in urine are generally increased in patients with UC when compared to urological and population controls (1321.0 versus 701.3 and 475.6 pg/mg creatinine, respectively). However, significantly increased TGFBI was predominantly found in muscle invasive (14,411.7 pg/mg creatinine), high-grade (8190.7 pg/mg) and de novo UC (1856.7 pg/mg; all p < 0.0001). Knockdown experiments in vitro led to a significant decline of cell proliferation and migration. In summary, our results suggest a critical role of TGFBI in UC tumorigenesis and particularly in high-risk UC patients with poor prognosis and an elevated risk of progression on the molecular level.

4.
Int J Hyg Environ Health ; 222(8): 1084-1092, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31378638

RESUMO

DINCH (cyclohexane-1,2-dicarboxylic acid-diisononyl ester) is a phthalate plasticizer substitute introduced into the market in 2002. It is increasingly used especially in the production of toys, food contact materials and medical devices. In this measurement campaign on 24-h urine samples of young adults (20-29 years) from the German Environmental Specimen Bank (ESB) collected in 2010, 2011, 2013, 2015 and 2017 (in total 300 samples, 60 samples/year) we analyzed three specific, oxidized DINCH metabolites (OH-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester; cx-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(carboxy-isooctyl) ester, oxo-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester). We merged these data with earlier data of the ESB from the years 1999-2012 and are now able to report levels and time trends of internal DINCH exposure from 1999 to 2017. After first detections of the major oxidized DINCH metabolite OH-MINCH in 2006 (6.7%) detection rates rapidly increased to 43.3% in 2009, 80% in 2010 and 98.3% in 2011 and 2012. From the year 2013 on we could detect OH-MINCH in every urine sample analyzed. The median concentrations of OH-MINCH rapidly increased from 0.15 µg/L in 2010 to twice the concentration in 2011 (0.31 µg/L) with further increases in 2013 (0.37 µg/L), 2015 (0.59 µg/L) and 2017 (0.70 µg/L). Similar increases, albeit at lower detection rates and concentration levels, could be observed for cx-MINCH and oxo-MINCH. All metabolites strongly correlate with each other. For the ESB study population, DINCH exposures are still far below health based guidance values such as the German Human Biomonitoring Value (HBM-I; 4,500 µg/L for the sum of OH-MINCH and cx-MINCH) or the tolerable daily intake (TDI) of EFSA (1 mg/kg bw/d). The median daily DINCH intake (DI) calculated for 2017 was 0.23 µg/kg bw/d, thus 4,310-times lower than the TDI. The maximum DI calculated for one individual in 2012 (42.60 µg/kg bw/d) was a factor of more than 20 below the TDI. The ongoing increase in DINCH exposure needs to be closely monitored in the future, including populations with potentially higher exposures such as children. This close monitoring will enable timely exposure and risk reduction measures if exposures reached critical levels, or if new toxicological data lead to lower health based guidance values. DINCH belongs to the European Human Biomonitoring Initiative (HBM4EU) priority substances for which policy relevant questions still have to be answered.

5.
Lung ; 197(5): 641-649, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31267149

RESUMO

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM. METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016. RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively. CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

6.
PLoS One ; 14(7): e0219087, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31276523

RESUMO

BACKGROUND: We compared psychomotor vigilance in female shift workers of the Bergmannsheil University Hospital in Bochum, Germany (N = 74, 94% nurses) after day and night shifts. METHODS: Participants performed a 3-minute Psychomotor Vigilance Task (PVT) test bout at the end of two consecutive day and three consecutive night shifts, respectively. Psychomotor vigilance was analyzed with respect to mean reaction time, percentage of lapses and false starts, and throughput as an overall performance score, combining reaction time and error frequencies. We also determined the reaction time coefficient of variation (RTCV) to assess relative reaction time variability after day and night shifts. Further, we examined the influence of shift type (night vs. day) by mixed linear models with associated 95% confidence intervals (CI), adjusted for age, chronotype, study day, season, and the presence of obstructive sleep apnea (OSA). RESULTS: At the end of a night shift, reaction times were increased (ß = 7.64; 95% CI 0.94; 14.35) and the number of lapses higher compared to day shifts (exp(ß) = 1.55; 95% CI 1.16-2.08). By contrast, we did not observe differences in the number of false starts between day and night shifts. Throughput was reduced after night shifts (ß = -15.52; 95% CI -27.49; -3.46). Reaction times improved across consecutive day and night shifts, whereas the frequency of lapses decreased after the third night. RTCV remained unaffected by both, night shifts and consecutive shift blocks. DISCUSSION: Our results add to the growing body of literature demonstrating that night-shift work is associated with decreased psychomotor vigilance. As the analysis of RTCV suggests, performance deficits may selectively be driven by few slow reactions at the lower end of the reaction time distribution function. Comparing intra-individual PVT-performances over three consecutive night and two consecutive day shifts, we observed performance improvements after the third night shift. Although a training effect cannot be ruled out, this finding may suggest better adaptation to the night schedule if avoiding fast-changing shift schedules.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31346764

RESUMO

PURPOSE: Due to a potential exposure to several definite or probable carcinogens, the IARC classified manufacturing of art glass, glass containers, and pressed ware as probably carcinogenic to humans in 1993 (Group 2A). Purpose of this study was to update the evidence from recently published scientific reports. METHODS: We searched for peer-reviewed articles published between 1993 and 2018 and combined result in terms of a meta-analysis. Overall, we considered twelve articles for a meta-analytic approach published after 1992. RESULTS: From a meta-analysis we derived a standardized incidence ratio (mSIR) and a standardized mortality ratio (mSMR) for lung cancer in men of 1.25 (95% CI 0.97-1.59) and 1.41 (95% CI 1.11-1.77), respectively. The estimated odds ratio (mOR) from five case-control studies was 1.25 (95% CI 0.90-1.73). Associated with an employment in glass factories, the estimated mSMR for larynx cancer was 2.38 (95% CI 1.23-4.16) based on two cohort studies; the mOR from four case-control studies was 1.35 (95% CI 0.73-2.52). Reports on elevated cancer risks at other sites were not consistent. CONCLUSIONS: Only few studies assessed cancer risk solely in glass workers. Gained evidence from more recent reports supports the IARC rating from 1993. Our combined results add limited evidence to a moderately elevated risk for cancer of the airways.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31233945

RESUMO

Di(2-ethylhexyl) adipate (DEHA) is a plasticizer and phthalate substitute used in various consumer products. Relevant population exposures have to be assumed. In this study we describe the determination of three specific side chain-oxidized monoester metabolites of DEHA, mono-2-ethyl-5-hydroxyhexyl adipate (5OH-MEHA), mono-2-ethyl-5-oxohexyl adipate (5oxo-MEHA), and mono-5-carboxy-2-ethylpentyl adipate (5cx-MEPA) in human urine as potential biomarkers of DEHA exposure. After enzymatic hydrolysis, urine samples were analyzed by online turbulent flow chromatography for matrix depletion and analyte enrichment coupled to liquid chromatography-electrospray ionization-triple quadrupole-tandem mass spectrometry (online-SPE-LC-MS/MS). For quantification stable isotope dilution was applied with limits of quantification of 0.05 µg/L for 5cx-MEPA and 5OH-MEHA, and 0.1 µg/L for 5oxo-MEHA. Method accuracies (relative recoveries) were between 92 and 109%, and relative standard deviations <5%. We investigated the applicability of the method for internal DEHA exposure assessment in six volunteers who had consumed food wrapped in commercial PVC-cling film containing DEHA and in two small pilot populations without known DEHA exposure (44 pregnant Brazilian women and 32 German adults). In the cling film experiment, we could quantify all three metabolites in all post exposure urine samples, with 5cx-MEPA being most prominent (0.30-10.2 µg/L), followed by 5OH-MEHA (0.12-4.31 µg/L) and 5oxo-MEHA (0.12-2.84 µg/L). In the Brazilian and German samples we could detect DEHA exposures in 43 and 9% of all samples, again with 5cx-MEPA as the most prominent metabolite. Based on validation and pilot biomonitoring results, the method has proven appropriate for DEHA biomonitoring and will be applied in future metabolism and population studies.

9.
Mol Pharmacol ; 96(2): 138-147, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31189668

RESUMO

ATP-binding cassette (ABC) transporters such as ABCB1 (P-glycoprotein), ABCC1 (MRP1), and ABCG2 (BCRP) are well known for their role in rendering cancer cells resistant to chemotherapy. Additionally, recent research provided evidence that, along with other ABC transporters (ABCA1 and ABCA7), they might be cornerstones to tackle neurodegenerative diseases. Overcoming chemoresistance in cancer, understanding drug-drug interactions, and developing efficient and specific drugs that alter ABC transporter function are hindered by a lack of in vivo research models, which are fully predictive for humans. Hence, the humanization of ABC transporters in mice has become a major focus in pharmaceutical and neurodegenerative research. Here, we present a characterization of the first Abcc1 humanized mouse line. To preserve endogenous expression profiles, we chose to generate a knockin mouse model that leads to the expression of a chimeric protein that is fully human except for one amino acid. We found robust mRNA and protein expression within all major organs analyzed (brain, lung, spleen, and kidney). Furthermore, we demonstrate the functionality of the expressed human ABCC1 protein in brain and lungs using functional positron emission tomography imaging in vivo. Through the introduction of loxP sites, we additionally enabled this humanized mouse model for highly sophisticated studies involving cell type-specific transporter ablation. Based on our data, the presented mouse model appears to be a promising tool for the investigation of cell-specific ABCC1 function. It can provide a new basis for better translation of preclinical research.

10.
Am J Ind Med ; 62(8): 663-671, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31168929

RESUMO

BACKGROUND: Fractional exhaled nitric oxide (FeNO) before and after specific inhalation challenge has been postulated as an additional tool in the diagnosis of occupational asthma (OA), but little is known about serial FeNO measurements at home and at work. The aim of the present study was to assess the contribution of serial measurements of FeNO off and at work toward the diagnosis of OA. METHODS: Forty-one subjects with suspected (n = 35) or diagnosed (n = 6) OA performed FeNO measurements once daily during a 2-week holiday and a subsequent 2-week work period. A work-related increase in FeNO by 20 ppb (parts per billion) or more was considered positive. Subjects with negative or doubtful specific inhalation challenge but a FeNO increase of 20 ppb or more were evaluated individually by an overall expert rating taking into account all available information. RESULTS: Seven of 35 subjects (20%) with suspected and three of six subjects (50%) with diagnosed OA showed a work-related FeNO increase of 20 ppb or more. Six of the seven with suspected OA were reclassified as having an OA diagnosis by the overall expert rating which also considered these FeNO changes. CONCLUSIONS: Serial FeNO measurements off and at work provide complementary information in the diagnosis in about one-fifth of cases with suspected OA, especially if specific inhalation challenges are negative or cannot be performed.

11.
Arch Toxicol ; 93(8): 2185-2195, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222524

RESUMO

Up to date, information on the validity of human biomonitoring (HBM) parameters of naphthalene exposure is poor. This study was performed to reveal the relation between occupational exposure to naphthalene and biological exposure markers. Therefore, ten lowly and highly exposed workers from the abrasives industry were selected to characterise a broad exposure range. Naphthalene in air was determined by personal air monitoring during one shift. For biological monitoring, pre- and post-shift urine samples collected on 2 days of a working week were analysed for 1,2-dihydroxynaphthalene (1,2-DHN), 1- and 2-naphthol, 1- and 2-naphthylmercapturic acid (NMA). The naphthalene concentration in air was in the range of 0.5 to 11.6 mg/m3. The biomarkers in urine showed post-shift concentration in the range of 114-51,809 µg/L for 1,2-DHN, 0.8-666 µg/L for 1-NMA, 2-2698 µg/L for 1-naphthol and 4-1135 µg/L for 2-naphthol, respectively. 2-NMA was not detected. The urinary levels increased significantly from pre- to post-shift for all analysed parameters and an accumulation over the working week was observed. Significant positive correlations were observed between 1,2-DHN, 1-NMA, 1- and 2-naphthol in post-shift urine samples and personal exposure to naphthalene in the air. 1-NMA and 1,2-DHN, 1- and 2-naphthol have been demonstrated as suitable biomarkers for naphthalene exposure monitoring. Of the determined biomarkers, 1,2-DHN is by far the metabolite with the highest concentration in the urine samples.

12.
Int Arch Occup Environ Health ; 92(7): 1067-1076, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31144109

RESUMO

PURPOSE: Increases of fractional exhaled nitric oxide (FeNO), sputum eosinophils, and methacholine responsiveness have been described after specific inhalation challenges (SIC) with occupational allergens, but limited information is available about their comparative performance. It was the aim of the study to assess the diagnostic accuracy of these non-invasive tests before and after SIC for the diagnosis of occupational asthma (OA). METHODS: A total of 122 subjects with work-related shortness of breath were included. The 'gold standard' was defined as airway obstruction (pulmonary responders) and/or an increase of FeNO of at least 13 ppb after SIC. The results were compared with those obtained using the pulmonary responder status alone as 'gold standard'. RESULTS: If the pulmonary responder status and/or an increase of FeNO was used as 'gold standard' for SIC, 28 out of 39 positives (72%), but also 20 out of 83 negatives (24%) showed an increase of sputum eosinophils and/or bronchial hyperresponsiveness after SIC. If the pulmonary responder status alone was used as 'gold standard', an increase of FeNO with a sensitivity of 0.57 and a specificity of 0.82 showed a higher accuracy than increases of sputum eosinophils (0.52/0.75) or bronchial hyperresponsiveness (0.43/0.87). Individual case analyses suggest that a few cases of OA may be detected by increases of sputum eosinophils or bronchial hyperresponsiveness alone, but probably false-positive tests dominate. CONCLUSION: It is recommended to use both lung function and increase of FeNO as primary effect parameters of SIC. Changes of sputum eosinophils and bronchial hyperresponsiveness after SIC have a low additional diagnostic value, but may be useful in individual cases.

13.
Int J Cancer ; 145(6): 1701, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31081941
14.
Toxicol Lett ; 309: 35-41, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30953687

RESUMO

The UV filter 2-ethylhexyl salicylate (EHS) is used in sunscreens and other personal care products worldwide and has been found in a variety of environmental media. We aimed to provide human toxicokinetic data on EHS as a tool for risk assessment. For that purpose, we investigated metabolism and urinary metabolite excretion after a single oral EHS dose (57.4-75.5 µg/(kg body weight)) in three male volunteers. In a suspect screening, we tentatively identified seven EHS metabolites. Three EHS specific metabolites were quantitatively investigated: 2-ethyl-5-hydroxyhexyl 2-hydroxybenzoate (5OH-EHS), 2-ethyl-5-oxohexyl 2-hydroxybenzoate (5oxo-EHS), and 5-(((2-hydroxybenzoyl)oxy)methyl)heptanoic acid (5cx-EPS). These metabolites were excreted with urinary excretion fractions of 0.28% (range: 0.13-0.54%), 0.11% (0.06-0.20%), and 0.24% (0.14-0.41%), respectively. The elimination was fast: peak urinary concentrations were found 1.6-2.6 h after dose and ≥95% of the total amounts were excreted within 24 h. Elimination kinetics were biphasic, with mean elimination half-lives of 0.8 h (first phase) and 6.6 h (second phase) for 5OH-EHS, 0.8 h and 6.3 h for 5oxo-EHS, and 1.1 h and 5.9 h for 5cx-EPS. After dermal exposure (sunscreen application), we found a considerably delayed EHS elimination. Based on urinary metabolite levels we calculated EHS exposure levels for a small pilot population.


Assuntos
Salicilatos/metabolismo , Protetores Solares/metabolismo , Administração Oral , Adulto , Biomarcadores , Eliminação Cutânea , Exposição Ambiental , Humanos , Masculino , Medição de Risco , Pele/metabolismo
15.
Toxicol In Vitro ; 58: 215-223, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30928694

RESUMO

Biopersistent pro-inflammatory fibers are suspected human carcinogens. Cytotoxicity and transcription of pro- and anti-inflammatory mediators of different fibers were investigated in functional relationship to chemotaxis in vitro as a model for fiber-induced inflammation of the lung. We challenged NR8383 rat macrophages with multi-walled carbon nanotubes (MWCNT) and various asbestos fibers. The resulting cell supernatants were than studied using the Particle-induced Cell Migration Assay (PICMA) and cytotoxicity was determined using the LDH test. Expression of inflammatory mediators was analyzed with qPCR and verified by ELISA. Chrysotile A and the rigid, needle-shaped NM-401 caused the strongest cytotoxic effects and the largest number of migrated cells. In contrast, the MWCNT NM-400, NM-402, and NM403 were apparently non-cytotoxic but induced pronounced cell migration showing a very steep dose response. However, the strength of cell migration and cytotoxicity of the asbestos fibers were correlated. The expression profile of inflammatory mediators was comparable, although cytotoxicity of the MWCNT NM-401 and NM-403 differed strongly. Induction of the corresponding proteins was confirmed for CCL2, CCL3, CXCL1, CXCL3, IL1RA (IL1RN), CSF1, GDF15 and TNFa. Chrysotile A and NM-401 induced much stronger chemotaxis than the non-fibrous particles reported in our previous study. Cytotoxic and chemotactic effects correspond to the induction of inflammatory mediators.

16.
Int J Cancer ; 145(10): 2861-2872, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31008534

RESUMO

Urothelial cancer (UCa) is the most predominant cancer of the urinary tract and noninvasive diagnosis using hypermethylation signatures in urinary cells is promising. Here, we assess gender differences in a newly identified set of methylation biomarkers. UCa-associated hypermethylated sites were identified in urine of a male screening cohort (n = 24) applying Infinium-450K-methylation arrays and verified in two separate mixed-gender study groups (n = 617 in total) using mass spectrometry as an independent technique. Additionally, tissue samples (n = 56) of mixed-gender UCa and urological controls (UCt) were analyzed. The hypermethylation signature of UCa in urine was specific and sensitive across all stages and grades of UCa and independent on hematuria. Individual CpG sensitivities reached up to 81.3% at 95% specificity. Albeit similar methylation differences in tissue of both genders, differences were less pronounced in urine from women, most likely due to the frequent presence of squamous epithelial cells and leukocytes. Increased repression of methylation levels was observed at leukocyte counts ≥500/µl urine which was apparent in 30% of female and 7% of male UCa cases, further confirming the significance of the relative amounts of cancerous and noncancerous cells in urine. Our study shows that gender difference is a most relevant issue when evaluating the performance of urinary biomarkers in cancer diagnostics. In case of UCa, the clinical benefits of methylation signatures to male patients may outweigh those in females due to the general composition of women's urine. Accordingly, these markers offer a diagnostic option specifically in males to decrease the number of invasive cystoscopies.

17.
Biopreserv Biobank ; 17(4): 312-318, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30882231

RESUMO

Legal and ethical demands for more transparent and strict data protection measures to enhance research participant privacy have grown with an increasing number of human biobanks providing biomaterial collections long term for unspecified future research questions. The design of a data protection scheme that minimizes the risk of donor reidentification and promotes biomaterial and data use in research is a big challenge to all kinds of human biobanks. Yet, there is a lack of publications which address this basic building block of a biobank. In this study, we present the data protection concept of our project driven, stand-alone biobank, focusing on meeting two biomaterial and data management areas simultaneously: operation of primary research projects involved in sample collection and long-term provision of biomaterial for future research purposes. The concept is based on national and international laws and ethical demands. Since the presented measures are transparent and basic, they should encourage biobanks in defining their own data protection concept and be easily transferable to different legal requirements.

18.
Sci Total Environ ; 653: 1025-1033, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30759543

RESUMO

Light is the strongest zeitgeber currently known for the synchronization of the human circadian timing system. Especially shift workers are exposed to altered daily light profiles. Our objective is the characterization of differences in blue-light exposures between day and night shift taking into consideration modifying factors such as chronotype. We describe 24-hour blue-light profiles as measured with ambient light data loggers (LightWatcher) during up to three consecutive days with either day or night shifts in 100 female hospital staff including 511 observations. Linear mixed models were applied to analyze light profiles and to select time-windows for the analysis of associations between shift work, individual factors, and log mean light exposures as well as the duration of darkness per day. Blue-light profiles reflected different daily activities and were mainly influenced by work time. Except for evening (7-9 p.m.), all time windows showed large differences in blue-light exposures between day and night shifts. Night work reduced the duration of darkness per day by almost 4 h (ß^ = -3:48 hh:mm, 95% CI (-4:27; -3.09)). Late chronotypes had higher light exposures in the morning and evening compared to women with intermediate chronotype (e.g. morning ß^ = 0.50 log(mW/m2/nm), 95% CI (0.08; 0.93)). Women with children had slightly higher light exposures in the afternoon than women without children (ß^ = 0.48, 95% CI (-0.10; 1,06)). Time windows for the description of light should be chosen carefully with regard to timing of shifts. Our results are helpful for future studies to capture relevant light exposure differences and potential collinearities with individual factors. Improvement of well-being of shift workers with altered light profiles may therefore require consideration of both - light at the workplace and outside working hours.


Assuntos
Recursos Humanos em Hospital , Exposição à Radiação/análise , Jornada de Trabalho em Turnos , Adulto , Ritmo Circadiano , Feminino , Alemanha , Humanos , Modelos Lineares , Pessoa de Meia-Idade
19.
Arch Toxicol ; 93(4): 921-929, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30729276

RESUMO

The toxicokinetics of N-ethyl-2-pyrrolidone (NEP), an embryotoxic organic solvent, has been studied in Sprague-Dawley rats after oral exposure. NEP and its metabolites 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI) were measured in plasma of pregnant and non-pregnant rats, and fetuses after NEP administration by gavage for 14 consecutive days at 50 mg/kg/day, and in plasma of non-pregnant rats after a single NEP administration. Additionally, amniotic fluid and 24-h urine samples of the pregnant rats were analyzed for NEP metabolites. Furthermore, 24-h urine samples from a repeated dose 28-day oral toxicity study in female (non-pregnant) and male rats administered developmentally non-toxic (0, 5, and 50 mg/kg/day) or toxic (250 mg/kg/day) doses of NEP were analyzed. Median peak plasma concentrations in non-pregnant rats after a single dose and repeated doses were 551 and 611 (NEP), 182 and 158 (5-HNEP), and 63.8 and 108 µmol/L (2-HESI), respectively; whereas in pregnant rats and fetuses 653 and 619 (NEP), 80.5 and 91.7 (5-HNEP) and 77.3 and 45.7 µmol/L (2-HESI) were detected. Times to reach maximum plasma concentrations for NEP, 5-HNEP, and 2-HESI were 1, 4, and 8 h, respectively, and were comparable to N-methyl-2-pyrrolidone (NMP) and its corresponding metabolites. In pregnant rats, plasma elimination of NEP and metabolite formation/elimination was much slower compared to non-pregnant rats and efficient placental transfer of NEP was observed. Our data, overall, suggest differences in the toxicokinetics of chemicals between pregnant and non-pregnant rats which need to be addressed in risk assessment, specifically when assessing developmental toxicants such as NEP.

20.
J Epidemiol Community Health ; 73(6): 489-495, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30804047

RESUMO

BACKGROUND: Associations of socioeconomic status (SES) and smoking-related diseases depend on uniform validity of self-reported smoking habits in different SES groups. We investigated the influence of SES on validity of self-reported smoking status by means of urinary cotinine. METHODS: We determined total urinary cotinine in the baseline population of the Heinz Nixdorf Recall Study. Participants with cotinine>200 µg/L were potential current smokers. We defined upper and lower 20% of the gender-specific distribution of the International Socio-Economic Index (ISEI) as high and low SES, respectively, else as intermediate. We analysed the association of self-reported smoking status and cotinine by ISEI and additional SES measures, stratified by gender. In self-reported non-smokers, we estimated age-adjusted ORs with 95% CI to detect differences by SES in the validity of self-reported smoking status. RESULTS: In 2004 men and 1887 women, 78% and 80%, respectively, reported to be non-smokers. Median cotinine concentrations were 2 µg/L in non-smokers, and 3651 µg/L in male and 3127 µg/L in female smokers. Based on cotinine in non-smokers, 2.0 % of men (n = 32) and 1.8 % of women (n = 27) were potential smokers, with lower proportions in the subgroup of never-smokers (men: 0.7%, women: 0.5%). The validity of self-reported smoking status did not substantially differ by SES. Tendencies for increased underreporting were indicated for women with low ISEI (OR 1.35; 95% CI 0.54 to 3.39) and men in blue-collar jobs (OR 1.39; 95% CI 0.67 to 2.87). CONCLUSION: Validity of self-reported smoking status in this elderly German cohort was high and did not depend on SES.

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