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1.
J Agric Food Chem ; 67(41): 11536-11541, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31589045

RESUMO

Limited reports on the use of nanobodies (Nbs) in fluorescence polarization immunoassay (FPIA) aroused us to explore if the small size of Nbs is a drawback for the development of sensitive FPIA to small molecular compounds, particularly since FPIA is a technology strongly dependent on molecular weight. In the present work, three different molecular weight Nbs against 3-phenoxybenzoic acid (3-PBA), an exposure biomarker of pyrethroid insecticides, including bare Nbs (15 kDa), Nbs-Avidin (Nbs-AV, 60 kDa), and Nbs-Alkaline phosphatase (Nbs-AP, 130 kDa) were specifically generated to cover distinct regions on the polarization and molecular weight relationship curve for a fluorescein tracer. In competitive FPIA, similar half-maximal inhibitory concentrations (IC50) of 3-PBA of 16.4, 12.2, and 14.8 ng mL-1 were obtained for Nbs, Nbs-AV, and Nbs-AP, respectively, indicating that the size of Nbs in the range tested had no significant effect on the sensitivity of the resulting competitive FPIA. An IC50 of 20.2 ng mL-1 for an anti-3-PBA polyconal antibody based FPIA further demonstrated the performance of Nbs, which was comparable to that of traditional antibodies in FPIA. Spike-recovery studies showed good and reproducible recovery of 3-PBA in urine samples, demonstrating the applicability of Nb-based FPIA. Overall, our results show that Nb-based FPIA achieves sensitivity levels of FPIA based on conventional antibodies and further indicate that Nb absolutely meets the sensitivity requirement of FPIA.


Assuntos
Benzoatos/urina , Imunoensaio de Fluorescência por Polarização/métodos , Inseticidas/toxicidade , Piretrinas/toxicidade , Anticorpos de Domínio Único/química , Biomarcadores/urina , Exposição Ambiental/análise , Imunoensaio de Fluorescência por Polarização/instrumentação , Humanos , Inseticidas/análise , Piretrinas/análise , Sensibilidade e Especificidade
2.
Se Pu ; 37(8): 815-823, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642251

RESUMO

Phthalates (PAEs) are a class of endocrine-disrupting chemicals. In recent years, the harmful effects of PAEs on human health, in particular their toxicity toward the reproductive system and development, have received significant attention because of their increasing production and usage. PAEs are ubiquitous in the environment and food products, resulting in unavoidable and long-term exposure in humans. Therefore, exposure and risk assessments of PAEs in humans are necessary. Screening and quantification of phthalate metabolites in urine is an important method for evaluating PAEs exposure, and establishing accurate analytical methods for this purpose has become a high priority. Phthalate monoesters and secondary metabolites are the most commonly targeted biomarkers of exposure to short-and long-chain PAEs, respectively. The combination of off-line or on-line solid phase extraction (SPE) with high performance liquid chromatography-tandem mass spectrometry has become the preferred method for the determination of phthalate metabolites. This paper reviews the analytical methods available for the detection of urinary phthalate metabolites and discusses the advantages, limitations, and challenges presented by each method in practical applications.


Assuntos
Biomarcadores/urina , Ácidos Ftálicos/urina , Exposição Ambiental , Humanos , Extração em Fase Sólida , Espectrometria de Massas em Tandem
3.
Rev Lat Am Enfermagem ; 27: e3194, 2019 Oct 14.
Artigo em Português, Inglês, Espanhol | MEDLINE | ID: mdl-31618387

RESUMO

OBJECTIVE: using the urinary cotinine biomarker to verify the occurrence of green tobacco sickness in workers who cultivate Burley tobacco. METHOD: paired case-control study, based on smoking status and on the 1:4 ratio, with participation of 20 case workers and 91 controls. Data collection included household surveys and urine collection for cotinine examination. Student's T-Test, the Mann-Whitney test, Pearson's chi-square or Fisher's exact tests were used. RESULTS: of the 23 suspected cases, 20 showed elevated levels of cotinine, signs and symptoms of headache, skin irritation, nausea, sickness and general malaise, especially in the morning. Most had worked with tobacco that was wet from the morning dew and when the weather was warm. CONCLUSION: there are signs suggestive of green tobacco sickness in Burley tobacco workers. The action of health professionals is necessary for the development of health promotion and preventive actions addressing work-related illness.


Assuntos
Doenças dos Trabalhadores Agrícolas/diagnóstico , Cotinina/urina , Exposição Ocupacional/análise , Adulto , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/urina , Biomarcadores/urina , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Cefaleia/induzido quimicamente , Humanos , Indicadores e Reagentes/análise , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Nicotina/envenenamento , Exposição Ocupacional/efeitos adversos , Equipamento de Proteção Individual , Inquéritos e Questionários , Tabaco/envenenamento
4.
Medicine (Baltimore) ; 98(37): e17143, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517857

RESUMO

The aim of this study was to investigate the alterations of urinary microRNA (miRNA) expression and explore its clinical significance in patients with chronic hepatitis B (CHB).The expression levels of urinary miRNA were detected by miRNA microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 106 CHB and 40 healthy controls (Ctrl) subjects. The correlation between the levels of miRNA expression and clinical characteristics were analyzed. Receiver-operator characteristic (ROC) curves were generated to determine the specificity and sensitivity of each individual miRNA. MiRNAs expression were further measured by PCR from exosomes, which were isolated from urine samples. LX2 cells were transfected with miRNA inhibitor and accumulation of cytoplasmic lipid droplets was analyzed by Oil Red O staining.miRNA expression profile analysis showed that 22 miRNAs were upregulated and 55 miRNAs were downregulated in CHB patients compared with Ctrl subjects (fold-change>1.5 and P < .05). miR-92b-3p, miR-770-5p, miR-5196-5p, and miR-7855-5p were significantly higher (P < .0001) in CHB subjects than in Ctrl subjects. ROC curve analysis showed that these four miRNAs were sensitive and specific enough to distinguish CHB and Ctrl subjects. The levels of miR-92b-3p expression were negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and APOA-1. Moreover, in vitro experiments indicated that inhibition of miR-92b-3p increased lipid droplet formation in LX2 cells.Aberrant expression of miRNAs has been observed in urine of CHB patients. Our findings may provide novel insights into the pathogenesis of CHB and may assist in the diagnosis of patients with CHB.


Assuntos
Hepatite B Crônica/urina , MicroRNAs/urina , Adulto , Biomarcadores/urina , Linhagem Celular , Exossomos/metabolismo , Feminino , Expressão Gênica , Humanos , Gotículas Lipídicas/metabolismo , Masculino , Sensibilidade e Especificidade
5.
Toxicol Lett ; 316: 20-26, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31465813

RESUMO

Health-care personnel handling antineoplastic drugs could be at risk for adverse health effects. We aimed to evaluate genotoxic and cytotoxic effects of antineoplastic drug exposure of personnel preparing and administering such drugs in three Oncology Hospitals in Italy enrolling 42 exposed subjects and 53 controls. Furthermore, we aimed to study the possible influence of XRCC1 and hOGG1 DNA repair genes polymorphisms on genotoxicity induced on buccal cells. We performed workplace and personal monitoring of some drugs and used exposure diary informations to characterize the exposure. Urinary 5-FU metabolite (α-fluoro-ß-alanine) was measured. Buccal Micronucleus Cytome (BMCyt) assay was used to evaluate DNA damage and other cellular anomalies. GEM and 5-FU contamination was found in 68% and 42% of wipe/swab samples respectively. GEM deposition was found on workers' pads while no α-fluoro-ß-alanine was found. BMCyt-assay showed higher genotoxicity and cytotoxicity on nurses administering antineoplastics than on preparators and controls. Among micronucleus (MN) positive (with MN frequency higher than 1.5‰) exposed subjects, the percentage of those carrying XRCC1 mut/het genotype was higher than in MN positive-controls. Using the sensitive BMCyt assay, we demonstrated that handling antineoplastics still represents a potential occupational health risk for workers that should be better trained/informed regarding such risks.


Assuntos
Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Monitoramento Ambiental/métodos , Fluoruracila/efeitos adversos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Mucosa Bucal/efeitos dos fármacos , Recursos Humanos de Enfermagem no Hospital , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Enfermagem Oncológica , Adulto , Antineoplásicos/urina , Biomarcadores/urina , Estudos de Casos e Controles , DNA Glicosilases/genética , Desoxicitidina/efeitos adversos , Desoxicitidina/urina , Feminino , Fluoruracila/urina , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Exposição Ocupacional/prevenção & controle , Polimorfismo Genético , Medição de Risco , Fatores de Risco , Urinálise , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética
6.
Adv Exp Med Biol ; 1165: 607-623, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399987

RESUMO

Renal fibrosis is the common pathological pathway of progressive CKD. The commonly used biomarkers in clinical practice are not optimal to detect injury or predict prognosis. Therefore, it is crucial to develop novel biomarkers to allow prompt intervention. Urine serves as a valuable resource of biomarker discovery for kidney diseases. Owing to the rapid development of omics platforms and bioinformatics, research on novel urinary biomarkers for renal fibrosis has proliferated in recent years. In this chapter, we discuss the current status and provide basic knowledge in this field. We present novel promising biomarkers including tubular injury markers, proteins related to activated inflammation/fibrosis pathways, CKD273, transcriptomic biomarkers, as well as metabolomic biomarkers. Furthermore, considering the complex nature of the pathogenesis of renal fibrosis, we also highlight the combination of biomarkers to further improve the diagnostic and prognostic performance.


Assuntos
Biomarcadores/urina , Nefropatias/urina , Rim/patologia , Fibrose , Humanos
7.
Int J Sport Nutr Exerc Metab ; 29(5): 461-465, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31444314

RESUMO

The urinary excretion of hydroxyproline (Hyp), abundant in collagen protein, may serve as a biomarker of habitual collagen intake, assisting with investigations of current interest in the role of dietary collagen intake in supporting the synthesis of collagenous body tissues. This study investigated the time course of urinary Hyp excretion in "free-living," healthy, active males following the ingestion of a standardized bolus (20 g) of collagenous (gelatin and a hydrolyzed collagen powder) and dairy (calcium caseinate and hydrolyzed casein) proteins. The excretion of Hyp was assessed over a 24-hr period, separated into three collection periods: 0-6, 6-12, and 12-24 hr. Hyp was elevated for 0-6 hr after the consumption of collagen-containing supplements (gelatin 31.3 ± 8.8 mmol/mol and hydrolyzed collagen 33.7 ± 22.0 mmol/mol vs. baseline: gelatin 2.4 ± 1.7 mmol/mol and hydrolyzed collagen 2.8 ± 1.5 mmol/mol; p < .05), but not for the dairy protein supplements (calcium caseinate 3.4 ± 1.7 mmol/mol and hydrolyzed casein 4.0 ± 3.7 mmol/mol; p > .05). Therefore, urinary Hyp reflects an acute intake of collagenous protein, but is not suitable as a biomarker for quantifying habitual collagen intake, provided through regular dietary practices in "free-living," healthy, active males.


Assuntos
Colágeno/administração & dosagem , Hidroxiprolina/urina , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto , Biomarcadores/urina , Caseínas , Estudos Cross-Over , Suplementos Nutricionais , Ingestão de Alimentos , Humanos , Masculino
8.
Medicine (Baltimore) ; 98(33): e16848, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415412

RESUMO

BACKGROUND: The aim of this study was to investigate the expression of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in expressed prostatic secretions (EPSs) of patients with chronic prostatitis (CP) and the expression of prostatic exosomal protein (PSEP) in urine, and to evaluate its correlation with the condition. METHODS: Urine samples from 310 patients with CP (101 National Institutes of Health [NIH] II, 112 NIH IIIa, and 97 NIH IIIb, classified according to the US National Institutes of Health) and 110 control group subjects were collected. The samples were tested for PSEP by enzyme-linked immunosorbent assay (ELISA). At the same time, EPSs in 60 patients from 310 patients with CP and 20 control group subjects were collected. The levels of IL-10 and TNF-α in the collected samples that EPS were determined by double antibody sandwich ELISA. SPSS 23.0 statistical software was used for statistical analysis of the measured data. RESULTS: The level of PSEP in patients with CP was significantly higher than that in the control group (P < .001). The levels of TNF-α and IL-10 in the EPS of patients with NIH II and NIH IIIa CP were higher than those of the patients with NIH IIIb and the control group (P < .001). There was a positive correlation between PSEP and IL-10 and TNF-α, while TNF-α and IL-10 were also positively correlated. CONCLUSION: PSEP, TNF-α, and IL-10 may serve as a basis for the classification diagnosis of CP. Their combination can provide more accurate diagnostic information for clinical CP typing.


Assuntos
Exossomos/metabolismo , Interleucina-10/urina , Próstata/metabolismo , Prostatite/urina , Fator de Necrose Tumoral alfa/urina , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Pessoa de Meia-Idade , Prostatite/diagnóstico , Curva ROC , Adulto Jovem
9.
Environ Pollut ; 254(Pt A): 112921, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31394349

RESUMO

The associations between bisphenol analogues (BPs) exposure and oxidative damage was explored in this 3-year longitudinal study of 275 school children in East China. Nine BPs in first morning urine samples were measured to assess BPs exposure, and 8-hydroxydeoxyguanosine (8-OHdG) and 8-oxo-7,8-dihydroguanosine (8-OHG) were measured as biomarkers of oxidative DNA and RNA damage. Linear mixed model (LMM) was used for repeated measures analysis. School children were mainly exposed to BPA, BPS, BPF, and BPAF (detection frequencies: 97.9%, 42.2%, 13.3%, and 12.8%) with median concentrations of 1.55, 0.355, 0.236 and 0.238 µg g-1Cre, respectively. An interquartile range (IQR) increase in urinary BPA was significantly associated with 12.9% (95% CI: 6.1%, 19.6%) increase in 8-OHdG and 19.4% (95% CI: 11.7%, 27.1%) increase in 8-OHG, and for total of BPs (the sum of BPA, BPS, BPF, and BPAF), they were 17.4% (95% CI: 8.9%, 26.0%) for 8-OHdG and 25.9% (95% CI: 16.1%, 35.7%) for 8-OHG, respectively. BPS was positively associated with 8-OHG, but not with 8-OHdG. The study found positive associations of urinary levels of BPA and total BPs with 8-OHdG and 8-OHG and indicated that BPs exposure might cause oxidative RNA damage.


Assuntos
Compostos Benzidrílicos/urina , Dano ao DNA , Desoxiguanosina/análogos & derivados , Exposição Ambiental/análise , Poluentes Ambientais/urina , Fenóis/urina , Compostos Benzidrílicos/toxicidade , Biomarcadores/urina , Criança , China , DNA , Desoxiguanosina/urina , Poluentes Ambientais/toxicidade , Humanos , Estudos Longitudinais , Oxirredução , Estresse Oxidativo , Fenóis/toxicidade , RNA , Projetos de Pesquisa
10.
Chemosphere ; 235: 481-491, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31272008

RESUMO

Chlorinated alkyl and non-chlorinated aryl organophosphate flame retardants (OPFRs) and some brominated flame retardants (FR) were introduced as replacements for polybrominated diphenyl ethers (PBDEs) after PBDEs phase-out in 2004 and 2013. Organophosphorous (OP) insecticides are mainly used in agricultural settings since the Food Quality Protection Act of 1996 phased-out most residential uses of OP insecticides in the United States. Urinary metabolites of FRs and OPs are known exposure biomarkers to FRs and OP insecticides, respectively. For large population-based studies, concurrent quantification of these metabolites using a small urine volume is desirable, but until now was not possible. We developed an analytical approach to quantify in 0.2 mL urine 10 FRs and six OP insecticide metabolites: diphenyl phosphate, bis(1,3-dichloro-2-propyl) phosphate, bis(1-chloro-2-propyl) phosphate, bis(2-chloroethyl) phosphate, dicresyl phosphates, dibutyl phosphate, dibenzyl phosphate, 2,3,4,5-tetrabromobenzoic acid, 2-((isopropyl)phenyl)phenyl phosphate, 4-((tert-butyl)phenyl)phenyl phosphate, dimethyl phosphate, diethyl phosphate, dimethyl thiophosphate, dimethyl dithiophosphate, diethyl thiophosphate, and diethyl dithiophosphate. The method relies on enzymatic deconjugation, automated off-line solid phase extraction, high-performance liquid chromatography, and isotope dilution tandem mass spectrometry. Detection limits ranged from 0.05 to 0.5 ng mL-1, accuracy from 89 to 118%, and imprecision was <10%. . This method is the first to quantify simultaneously trace levels of 16 biomarkers of FRs and OP insecticides in only four drops of urine. We confirmed the method suitability for use in large epidemiological studies to assess background and occupational exposures to these classes of environmental pollutants by analyzing 303 samples collected from the general population and a group of firefighters. FR metabolite and DAPs concentrations in the general population group were lower than in the firefighters group, and within the ranges reported in the U.S. general population and other non-occupationally exposed populations.


Assuntos
Biomarcadores/urina , Exposição Ambiental/análise , Monitoramento Ambiental , Poluentes Ambientais/urina , Retardadores de Chama/toxicidade , Inseticidas/toxicidade , Organofosfatos/toxicidade , Plastificantes/toxicidade , Cromatografia Líquida de Alta Pressão/métodos , Poluentes Ambientais/análise , Retardadores de Chama/análise , Retardadores de Chama/metabolismo , Éteres Difenil Halogenados/análise , Halogenação , Humanos , Inseticidas/análise , Inseticidas/urina , Limite de Detecção , Espectrometria de Massas , Exposição Ocupacional/análise , Organofosfatos/metabolismo , Organofosfatos/urina , Fosfatos , Plastificantes/análise , Plastificantes/metabolismo , Extração em Fase Sólida
11.
Toxicol Lett ; 313: 169-177, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284021

RESUMO

Acute kidney injury (AKI) is a heterogeneous clinical syndrome with diverse outcomes. The recovery from AKI has prognostic importance. Little research has been done in order to find biomarkers that can predict recovery from AKI. Cav-2 is one of the main constituents of caveolae and is expressed in kidney. This study analyzed the time course of Cav-2 urinary excretion and renal expression in rats treated with cisplatin. Male Wistar rats were injected with cisplatin (5 mg/kg b.w., i.p.), and the studies were performed after 2, 4 and 14 days. Cav-2 abundance was evaluated in urine, in renal homogenates and in apical membranes by Western blotting. Cav-2 in urine was increased only 14 days after treatment, in the recovery phase of cisplatin-induced AKI. These results show that Cav-2 in urine could be useful as a biomarker of renal recovery, but not as an early biomarker of cisplatin-induced AKI. Cav-2 expression in total renal homogenates was not modified with treatment, but a down-regulation of Cav-2 in apical membranes was observed in treated animals. We hypothesize that Cav-2 internalizes into renal cells from their apical membrane in response to cisplatin, and regulates in this manner different signaling proteins involved in the physiopathology of renal damage.


Assuntos
Lesão Renal Aguda/urina , Caveolina 2/urina , Cisplatino , Rim/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/fisiopatologia , Animais , Biomarcadores/urina , Modelos Animais de Doenças , Rim/fisiopatologia , Masculino , Ratos Wistar , Recuperação de Função Fisiológica , Eliminação Renal , Fatores de Tempo
12.
Medicine (Baltimore) ; 98(28): e16278, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305409

RESUMO

To assess the effect of changing the sodium to potassium (Na/K) ratio on blood pressure at 4 years of follow-up.The measurements were carried out under identical conditions in two study periods (2008-2010 and 2012-2014). Urinary excretion of sodium and potassium (mmol/L) over 12 nocturnal hours was used to calculate the Na/K ratio and categorized by quintile. The 24-hour sodium and potassium intake was estimated using a validated equation. The mean BP was calculated from 3 measurements after 5 minutes of rest. Of the 15,105 participants at baseline, 14,014 completed the first follow-up. Participants without validated urine collection (n = 5,041), using antihypertensive medication (n = 3,860) at either time points or reporting bariatric surgery during follow-up (n = 45) were excluded. The differences between follow-up and baseline values were calculated for BP and the Na/K ratio. Analyses were stratified by sex and adjusted for confounding variables.Sodium intake did not change from baseline, but potassium intake increased by approximately 150 mg in both sexes (P < .001), with a consequent reduction of the Na/K ratio. The highest quintile of change in the Na/K ratio was associated with greater variation in BP. When adjusted for covariates, it is possible to observe an increase in SBP in women from the third quintile of the Na/K ratio, in men this increase was observed from the fourth quintile. However, for DBP this increase is observed from the third quintile in both men and women.Increase in SBP was observed in women from the third quintile of the Na/K ratio, in men this increase is observed from the fourth quintile. However, for DBP this increase is observed from the third quintile in both men and women. The Na/K ratio demonstrated a greater association in BP.


Assuntos
Pressão Sanguínea , Potássio/urina , Sódio/urina , Adulto , Idoso , Biomarcadores/urina , Pressão Sanguínea/fisiologia , Brasil , Dieta , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
13.
Int J Occup Environ Med ; 10(3): 124-136, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31325295

RESUMO

BACKGROUND: Coke oven workers are exposed to polycyclic aromatic hydrocarbons (PAHs) with possible genotoxicity and carcinogenicity. Metabolizing enzymes genes and DNA repair genes are suspected to be correlated with the level of DNA damage. They may contribute to variable individual sensitivity to DNA damage induced by PAHs exposure at workplace. OBJECTIVE: To investigate the relationship between biomarkers of PAHs: 1-hydroxypyrene (1-OHP), DNA adducts, and 8-hydroxy-2-deoxyguanosine (8-OHdG) in coke oven workers, and to assess the role of cytochrome P2E1 (CYP2E1) gene expression and DNA repairing gene (XRCC1) polymorphism in detecting workers at risk. METHODS: 85 exposed workers and 85 unexposed controls were enrolled into this study. Urinary 1-OHP, 8-OHdG, and BPDE-DNA adduct were measured. CYP2E1 gene expression and genotyping of XRCC1 399 Arg/Gln were evaluated by real-time PCR. RESULTS: The median urinary 1-OHP levels (6.3 µmol/mol creatinine), urinary 8-OHdG (7.9 ng/mg creatinine), DNA adducts (6.7 ng/µg DNA) in the exposed group were significantly higher than those in the unexposed group. Carriers of the variant allele (Gln) of XRCC1 had the highest levels of 1-OHP, DNA adducts and 8-OHdG, and the lowest level of CYP2E1 gene expression. In exposed workers, significant positive correlations were found between 1-OHP level and each of the work duration, 8-OHdG, and DNA adducts levels. There was a significant negative correlation between 1-OHP level and CYP2E1 gene expression. Work duration and CYP2E1 gene expression were predictors of DNA adducts level; 1-OHP level and work duration were predictors of urinary 8-OHdG level. CONCLUSION: Workers with higher exposure to PAH were more prone to oxidative DNA damage and cancer development. DNA adducts level reflects the balance between their production by CYP2E1 and elimination by XRCC1 gene.


Assuntos
Citocromo P-450 CYP2E1/genética , Adutos de DNA/genética , Desoxiguanosina/análogos & derivados , Monitoramento Ambiental/métodos , Exposição Ocupacional/análise , Pirenos/urina , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Adulto , Biomarcadores/urina , Coque , Citocromo P-450 CYP2E1/biossíntese , Adutos de DNA/urina , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/genética , Desoxiguanosina/urina , Egito , Humanos , Masculino , Pessoa de Meia-Idade , Hidrocarbonetos Policíclicos Aromáticos/urina , Polimorfismo Genético , Medição de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/biossíntese , Adulto Jovem
14.
Toxicol Lett ; 314: 133-141, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31325633

RESUMO

Hexavalent chromium (Cr(VI)) compounds are classified as carcinogenic to humans. Whereas chromium measurements in urine and plasma attest to the last few hours of total chromium exposure (all oxidation states of chromium), chromium in red blood cells (RBC) is attributable specifically to Cr(VI) exposure over the last few days. Before recommending Cr in RBC (CrIE) as a biological indicator of Cr(VI) exposure, in vivo studies must be undertaken to assess its reliability. The present study examines the kinetics of Cr(VI) in rat after a single intravenous dose of ammonium dichromate. Chromium levels were measured in plasma, red blood cells and urine. The decay of the chromium concentration in plasma is one-phase-like (with half-life time of 0.55 day) but still measurable two days post injection. The excretion of urinary chromium peaks between five and six hours after injection and shows large variations. Intra-erythrocyte chromium (CrIE) was very constant up to a minimum of 2 days and half-life time was estimated to 13.3 days. Finally, Cr(III) does not interfere with Cr(VI) incorporation in RBC. On the basis of our results, we conclude that, unlike urinary chromium, chromium levels in RBC are indicative of the amount of dichromate (Cr(VI)) in blood.


Assuntos
Carcinógenos Ambientais/administração & dosagem , Carcinógenos Ambientais/metabolismo , Cromo/administração & dosagem , Cromo/sangue , Eritrócitos/metabolismo , Administração Intravenosa , Animais , Biomarcadores/sangue , Biomarcadores/urina , Carga Corporal (Radioterapia) , Carcinógenos Ambientais/farmacocinética , Carcinógenos Ambientais/toxicidade , Cromo/farmacocinética , Cromo/toxicidade , Masculino , Modelos Biológicos , Oxirredução , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Especificidade da Espécie , Toxicocinética
15.
Chem Biol Interact ; 311: 108760, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31348916

RESUMO

1-Chloro-2-hydroxy-3-butene (CHB) is a possible metabolite of 1,3-butadiene, a carcinogenic air pollutant. To demonstrate its formation in vivo, it is desirable to develop a practical biomarker and the corresponding analysis method. CHB can undergo alcohol dehydrogenase- and cytochromes P450 enzymes (P450)-mediated oxidation to yield 1-chloro-3-buten-2-one (CBO), which readily forms glutathione conjugates. We hypothesized that CBO-derived mercapturic acids, which are the expected biotransformed products of CBO-glutathione conjugates, could be used as CHB biomarkers. Thus, in the present study, we investigated the in vivo biotransformation of CHB into CBO-derived mercapturic acids. Because the reaction of CBO with N-acetyl-l-cysteine yields two products, 1,4-bis(N-acetyl-S-cysteinyl)-2-butanone (NC1) and 1-chloro-4-(N-acetyl-S-cysteinyl)-2-butanone (NC2), we first developed an isotope dilution LC/ESI--MS-MS method to quantitate urinary NC1 and NC2, and then determined their concentrations in urine of C57BL/6 mice and Sprague-Dawley rats administered CHB. Since no NC2 was detected in samples, the LC/ESI--MS-MS method was optimized specifically for NC1. NC1 was enriched through solid phase extraction with the recovery being 75-82%. The limits of detection and quantitation were 6.8 and 34 fmol/0.1 mL for mouse urine, and 4.5 and 7.1 fmol/0.1 mL for rat urine, respectively. In urine of animals before CHB administration, no NC1 was detected; in mice administered CHB at 10 and 30 mg/kg, and rats at 5 and 15 mg/kg, NC1 was detected and its concentrations in urine from animals given higher doses were 3-6 fold higher than those given lower doses. Moreover, the NC1 concentrations in urine during 0-8 h were 4-6 fold and 10-11 fold higher than those during 8-24 h for mice and rats, respectively. The results demonstrated that CHB could be in vivo biotransformed into NC1, which could be used as a practical CHB biomarker.


Assuntos
Biomarcadores/urina , Butadienos/metabolismo , Butanóis/metabolismo , Espectrometria de Massas em Tandem , Acetilcisteína/química , Poluentes Atmosféricos/química , Animais , Butadienos/química , Butanóis/química , Cromatografia Líquida de Alta Pressão , Marcação por Isótopo , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley
16.
BMC Neurol ; 19(1): 154, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286894

RESUMO

BACKGROUND: Alzheimer's disease has become a public health crisis globally due to its increasing incidence. The purpose of this study was to establish an early warning model using artificial neural network (ANN) for early diagnosis of AD and to explore early sensitive markers for AD. METHODS: A population based nested case-control study design was used. 89 new AD cases with good compliance who were willing to provide urine and blood specimen were selected from the cohort of 2482 community-dwelling elderly aged 60 years and over from 2013 to 2016. For each case, two controls living nearby were identified. Biomarkers for AD in urine and blood, neuropsychological functions and epidemiological parameters were included to analyze potential risk factors of AD. Compared with logistic regression, k-Nearest Neighbor (kNN) and support vector machine (SVM) model, back-propagation neural network of three-layer topology structures was applied to develop the early warning model. The performance of all models were measured by sensitivity, specificity, accuracy, positive prognostic value (PPV), negative prognostic value (NPV), the area under curve (AUC), and were validated using bootstrap resampling. RESULTS: The average age of AD group was about 5 years older than the non-AD controls (P < 0.001). Patients with AD included a significantly larger proportion of subjects with family history of dementia, compared with non-AD group. After adjusting for age and gender, the concentrations of urinary AD7c-NTP and aluminum in blood were significantly higher in AD group than non-AD group (2.01 ± 1.06 vs 1.03 ± 0.43, 1.74 ± 0.62 vs 1.24 ± 0.41 respectively), but the concentration of Selenium in AD group (2.26 ± 0.59) was significantly lower than that in non-AD group (2.61 ± 1.07). All the models were established using 18 variables that were significantly different between AD patients and controls as independent variables. The ANN model outperformed the other classifiers. The AUC for this ANN was 0.897 and the model obtained the accuracy of 92.13%, the sensitivity of 87.28% and the specificity of 94.74% on the average. CONCLUSIONS: Increased risk of AD may be associated with higher age among senior citizens in urban communities. Urinary AD7c-NTP is clinically valuable for the early diagnosis. The established ANN model obtained a high accuracy and diagnostic efficiency, which could be a low-cost practicable tool for the screening and diagnosis of AD for citizens.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/sangue , Proteínas do Tecido Nervoso/urina , Redes Neurais (Computação) , Fragmentos de Peptídeos/sangue , Oligoelementos/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Área Sob a Curva , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Humanos , Masculino , Sensibilidade e Especificidade
17.
BMC Vet Res ; 15(1): 189, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174528

RESUMO

BACKGROUND: Perinatal mortality may vary between herds, but the cost of deaths are always higher than value of the calf. When diagnosing the cause of a calf's death it is important to determine when it occurred, before or after calving. Metabolomics is widely used to identify many human diseases, but quite rarely applied in veterinary science. The aim of this study was to compare the metabolic profiles of calves with different times of death and those of calves born alive. Into the study, twenty one healthy controls (singleton, normal assisted calving, born alive) and 75 stillborn (SB) calves (with a gestation length of ≥260 days, SB, or dead within 6 h of birth) were enrolled. Plasma and urine from SB and control calves were investigated by proton nuclear magnetic resonance based metabolomic methods. SB calves were divided into four PMI groups. One PMI group included calves that died after calving and the other groups - three comprised in utero deaths, based on pathophysiological changes (lung inflation, autolysis in internal organs, hemoglobin imbibition in the pleura and aortic arch). Partial Least Squares - Discriminant Analysis models based on plasma metabolites were calculated, reflecting assumed data clustering. RESULTS: Twenty six metabolites in plasma and 29 in urine changed significantly with PMI according to one way analysis of variance. Half the metabolites in plasma and the majority in urine increased with PMI. Six metabolites increased simultaneously in plasma and urine: acetate, sn-glycero-3-phosphocholine (GPC), leucine, valine, creatine, and alanine. CONCLUSIONS: Post-mortem changes in calves were associated with molecular variations in blood plasma and urine, showing the greatest differences for the group in which the post-mortem pathological changes were the most advanced. The results of the study show that evaluation of calf plasma or urine may be used as a diagnostic method for the determination of the PMI. Moreover, the metabolites, which unambiguously increased or decreased, can be used as potential biomarkers of PMI.


Assuntos
Bovinos/sangue , Bovinos/urina , Metaboloma , Natimorto/veterinária , Animais , Animais Recém-Nascidos/sangue , Animais Recém-Nascidos/urina , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Masculino , Gravidez , Resultado da Gravidez/veterinária , Espectroscopia de Prótons por Ressonância Magnética/métodos , Fatores de Tempo
18.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(5): 585-589, 2019 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-31177743

RESUMO

Objective: The urine concentrations of phthalate metabolites were used to estimate the cumulative risk assessment in preschool children in Ma'anshan of Anhui province. Methods: Based on the China-Anhui Birth Cohort, the demographic information and urine samples of 3 743 children were collected in Ma'anshan from April 2014 to April 2015. The concentrations of 7 metabolites' [monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl- 5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)] of 5 phthalates [dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), and di (2-ethylhexyl) phthalate (DEHP)] in the urine samples of the children were measured by solid-phase extration-triple quadrupole high performance liquid chromatography-tandem mass spectrometry-isotope method. In addition, the estimated daily intakes (EDIs) of 5 phthalates were calculated according to the metabolites' concentrations. Cumulative risk assessment was performed using hazard quotient (HQ) and hazard index (HI) methods. Results: The M (Q(R)) of seven metabolite concentrations were 29.58 (18.69-48.26), 26.65 (13.44-56.09), 256.86 (150.99-438.51), 0.12 (0.04-0.32), 6.27 (3.71-11.13), 17.94 (11.94-28.42) and 24.80 (16.05-40.32) µg/g creatinine, respectively. For the EDIs of 5 phthalates, DBP ranked first, followed by DEHP, DMP, DEP and BBzP with the M (Q(R)) of 7.54 (4.41-12.85), 3.35 (2.20-5.42), 0.75 (0.47-1.24), 0.71 (0.36-1.52) and 0.003 (0.001-0.009) µg/(kg·d), respectively. The HQ and HI varied with age, gender and sampling season, the differences were significant (P<0.05). Conclusions: These results indicated that risk of cumulative exposure to phthalates was high in preschool children aged 3-6 years in Ma'anshan. Age, gender and sampling season were influencing factors.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/urina , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/urina , Medição de Risco/métodos , Biomarcadores/urina , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino , Ácidos Ftálicos/efeitos adversos , Estações do Ano
19.
Chemosphere ; 234: 640-647, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31234081

RESUMO

Occupational exposure to metals can have an adverse effect on the cardiovascular system. However, epidemiological studies of the associations of metals expose with hypertension among occupationally exposed workers were limited. The aim of this study was to investigate the potential association between urinary metal levels and the risk of hypertension among molybdenum miners and iron and steel foundry workers. The cross-sectional study had 395 participants. Urinary metal levels were determined by inductively coupled plasma mass spectrometry. Log-binomial regression model and two-piece-wise regression model were applied to assess the dose-response relationship between metal exposure and hypertension. We observed that increased prevalence ratios for hypertension among the quartile of urinary concentrations of molybdenum, arsenic and lead were positive (all P for trend <0.05). Compared with the lowest quartiles, participants in the highest quartiles of molybdenum, arsenic and lead had a 2.58-fold, 4.30-fold and 4.85-fold increased probability of having hypertension, respectively. In the threshold effect analyses, we found the relationship was nonlinear between urinary molybdenum, cobalt, cadmium, arsenic and lead concentrations and the prevalence of hypertension. In addition, Pb, Mo, As and Co may have joint effect, and a strong positive correlation with the prevalence of hypertension. Conversely, the association between the joint effect of Cd, Pb and Mo versus the prevalence of hypertension is not significant. We provide reference levels of molybdenum, cobalt, cadmium, arsenic and lead that can be used to assess the effects of occupational metal exposure on hypertension.


Assuntos
Arsênico/urina , Cádmio/urina , Cobalto/urina , Hipertensão/urina , Chumbo/urina , Molibdênio/urina , Exposição Ocupacional/análise , Adulto , Biomarcadores/urina , Estudos Transversais , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino
20.
Anim Sci J ; 90(8): 1090-1095, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199550

RESUMO

Blood and urine were compared to clarify which is a better sample for estimating the concentration of radioactive cesium in muscles of live cattle. The most probable concentration of 137 Cs in muscles was 21.0 times that in blood, and the error of this estimation was 28%. The concentration of 137 Cs in blood was estimated accurately using urine samples. The estimation error did not increase so much (33%), even when the concentration of 137 Cs in muscles was estimated using urine samples. On the other hand, the maximum volume of blood that can be collected with one syringe is 50 ml, whereas it is easy to collect 1,000 ml of urine. It took at least 360 min to confirm that a cow meets the legal standard by inspecting 50 ml of blood. However, with 1,000 ml of urine, a 20 min measurement time was sufficient for this purpose. This difference in the required measurement time is critically important for practical use. In addition, urine can be collected by farmers themselves, whereas the blood collection requires a veterinarian. Therefore, urine is a more convenient and practical sample for estimating the contamination level of live cattle with radioactive cesium.


Assuntos
Bovinos/sangue , Bovinos/urina , Radioisótopos de Césio/sangue , Radioisótopos de Césio/urina , Exposição à Radiação/efeitos adversos , Exposição à Radiação/análise , Animais , Biomarcadores/sangue , Biomarcadores/urina , Radioisótopos de Césio/efeitos adversos , Acidente Nuclear de Fukushima
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