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1.
J Ethnopharmacol ; 300: 115752, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36174807

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Peganum harmala L. is a traditional medicinal plant used for centuries in folk medicine. It has a wide array of therapeutic attributes, which include hypoglycemic, sedative, anti-inflammatory, and antioxidant properties. The fruit decoction of this plant was claimed by Avicenna as traditional therapy for urolithiasis. Also, P. harmala seed showed a clinical reduction in kidney stone number and size in patients with urolithiasis. AIM OF THE STUDY: In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major ß-carboline alkaloids of P. harmala were investigated. MATERIALS AND METHODS: Extraction, isolation, and characterization of the major alkaloids were performed using different chromatographic and spectral techniques. The in vivo anti-urolithiatic action was evaluated using ethylene glycol (EG)-induced urolithiasis in rats by studying their mitigating effects on the antioxidant machinery, serum toxicity markers (i.e. nitrogenous waste, such as blood urea nitrogen, uric acid, urea, and creatinine), minerals (such as Ca, Mg, P, and oxalate), kidney injury marker 1 (KIM-1), and urinary markers (i.e. urine pH and urine output). RESULTS: Two major alkaloids, harmine (P1) and harmalacidine HCl (P2), were isolated and in vivo evaluated alongside the different extracts. The results showed that P. harmala and its constituents/fractions significantly reduced oxidative stress at 50 mg/kg body weight, p.o., as demonstrated by increased levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT) in kidney homogenate as compared to the EG-treated group. Likewise, the total extract, pet. ether fraction, n-butanol fraction, and P1, P2 alleviated malondialdehyde (MDA) as compared to the EG-treated group. Serum toxicity markers like blood urea nitrogen (BUN), creatinine, uric acid, urea, kidney injury molecule-1 (Kim-1), calcium, magnesium, phosphate, and oxalate levels were decreased by total extract, pet. ether fraction, n-butanol fraction, P1, and P2 as compared to the EG-treated group. Inflammatory markers like NFκ-B and TNF-α were also downregulated in the kidney homogenate of treatment groups as compared to the EG-treated group. Moreover, urine output and urine pH were significantly increased in treatment groups as compared to the EG-treated group deciphering anti-urolithiatic property of P. harmala. Histopathological assessment by different staining patterns also supported the previous findings and indicated that treatment with P. harmala caused a gradual recovery in damaged glomeruli, medulla, interstitial spaces and tubules, and brown calculi materials as compared to the EG-treated group. CONCLUSION: The current research represents scientific evidence on the use of P. harmala and its major alkaloids as an effective therapy in the prevention and management of urolithiasis.


Assuntos
Alcaloides , Cálculos Renais , Peganum , Urolitíase , 1-Butanol , Alcaloides/farmacologia , Animais , Antioxidantes , Cálcio , Oxalato de Cálcio/urina , Catalase , Creatinina , Éteres , Etilenoglicol/uso terapêutico , Etilenoglicol/toxicidade , Glutationa , Glutationa Peroxidase , Glutationa Redutase , Harmina , Hipnóticos e Sedativos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Cálculos Renais/tratamento farmacológico , Magnésio , Malondialdeído , Peganum/química , Fosfatos , Extratos Vegetais , Ratos , Fator de Necrose Tumoral alfa , Ureia , Ácido Úrico , Urolitíase/induzido quimicamente , Urolitíase/tratamento farmacológico , Urolitíase/patologia
2.
Talanta ; 251: 123816, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35963014

RESUMO

Benzodiazepines exhibit central nervous system depressive activity as well as sedative, hypnotic, and anticonvulsant properties, which enable to use them as medical treatment in anxiety, epilepsy, insomnia and alcohol withdrawal syndrome. However, from 2000s illegal benzodiazepine derivatives have started to emerge on illicit drug market as new psychoactive substances (NPSs) monitored in many countries. Analysis of both pharmaceutical drugs and NPSs from benzodiazepines group could be challenging, as usually very low concentrations need to be determined. Thus, an ultra-sensitive UHPLC-QqQ-MS/MS method was developed for simultaneous determination of 54 benzodiazepines (pharmaceutical drugs, NPS and their metabolites) and 3 z-drugs with one metabolite in biological fluid samples. The lower limit of quantification for most substances was 50 pg/mL, whereas for 17 substances as low as 10 pg/mL was achieved. Together with reduced sample volume to 100 µL it makes the developed method suitable for a sensitive multidrug toxicological analysis. Presented method was applied in routine toxicological practice as well as for the determination of benzodiazepines, z-drugs and their metabolites in 25 authentic biological fluids (blood, urine, vitreous humor and bile), both antemortem and postmortem. 19 different compounds, including benzodiazepines, their metabolites and z-drugs were determined. Antemortem blood concentrations were within 0.2-114.5 ng/mL, whereas concentrations in antemortem urine samples were 0.03-102.6 ng/mL. In postmortem specimens, concentrations ranged within 0.2-473.2 ng/mL, 0.5-94.1 ng/mL, 1.3-208.8 ng/mL and 41.5-42.0 ng/mL in blood, vitreous humor, urine and bile, respectively. The developed method is suitable for a forensic toxicology analysis, as well as clinical toxicology which is evidenced by the positive results of international proficiency tests.


Assuntos
Alcoolismo , Drogas Ilícitas , Síndrome de Abstinência a Substâncias , Anticonvulsivantes , Benzodiazepinas , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Hipnóticos e Sedativos , Drogas Ilícitas/urina , Espectrometria de Massas em Tandem/métodos
3.
J Proteomics ; 270: 104735, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36174949

RESUMO

Canine babesiosis is a tick-borne disease caused by Babesia canis, with acute kidney injury as one of the common complications. In the study 8 healthy control dogs and 22 dogs with naturally occurring babesiosis were enrolled, with the aim to analyse differences in serum and urinary proteomes between healthy dogs and dogs with different degree of renal dysfunction in babesiosis using a label-based high-throughput quantitative proteomic approach. In serum, 58 proteins were found differentially abundant between healthy controls and groups of dogs with different degrees of renal dysfunction in babesiosis, while in urine there were 259 differentially abundant proteins. In addition, altered biological pathways were detected in the diseased dogs using bioinformatics tools and validation of several candidate biomarkers was performed. SIGNIFICANCE: The main aim of this comprehensive study was to perform analyses of serum and urinary proteomes of dogs with renal dysfunction in babesiosis compared to healthy dogs using, for the first time, a high-throughput proteomic method and functional enrichment analyses. Serum and urine samples of the same dogs were investigated in order to gain a more complete picture of pathologic changes taking place in renal dysfunction in babesiosis. We highlighted two putative biomarkers validated herein which could be of importance for early diagnosis of renal dysfunction in canine babesiosis, as they are easily accessible from urine and their concentration rises before the appearance of azotaemia: urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary liver-type fatty acid-binding protein (L-FABP).


Assuntos
Babesiose , Doenças do Cão , Nefropatias , Cães , Animais , Babesiose/complicações , Babesiose/diagnóstico , Proteômica , Proteoma , Doenças do Cão/diagnóstico , Biomarcadores , Nefropatias/diagnóstico , Nefropatias/urina , Nefropatias/veterinária
4.
J Proteomics ; 270: 104737, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36174950

RESUMO

The exploration of nucleoside changes in human biofluids has profound potential for cancer diagnosis. Herein, we developed a rapid methodology to quantify 17 nucleosides by UHPLC-MS/MS. Five pairs of isomers were successfully separated within 8 min. The ME was mostly eliminated by sample dilution folds of 1000 for urine and 40 for CCS. The optimized method was firstly applied to screen potential nucleoside biomarkers in CCS by comprising bladder cancer cell lines (5637 and T24) and normal human bladder cell line SV-HUC-1 together with student's t-test and OPLS-DA. Nucleosides with significant differences in the supernatant of urine samples were also uncovered comparing BCa with the non-tumor group, as well as a comparison of BCa recurrence group with the non-recurrence group. By intersecting the differential nucleosides in CCS and urine supernatant, and then further confirmed using validation sets, the combination of m3C and m1A with AUC of 0.775 was considered as a potential biomarker for bladder cancer diagnosis. A panel of m3C, m1A, m1G, and m22G was defined as potential biomarkers for bladder cancer prognosis with an AUC of 0.819. Above all, this method provided a new perspective for diagnosis and recurrence monitoring of bladder cancer. SIGNIFICANCE: The exploration of nucleoside changes in body fluids has profound potential for the diagnosis and elucidation of the pathogenesis of cancer. In this study, we developed a rapid methodology for the simultaneous quantitative determination of 17 nucleosides in the supernatant of cells and urine samples using UHPLC-MS/MS to discover and validate bladder cancer related excreted nucleoside biomarkers. The results of this paper provide a new strategy for diagnosis and postoperative recurrence monitoring of bladder cancer and provide theoretical support for the exploration of its pathogenesis.


Assuntos
Líquidos Corporais , Neoplasias da Bexiga Urinária , Humanos , Espectrometria de Massas em Tandem/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/metabolismo , Nucleosídeos/urina , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Biomarcadores Tumorais , Líquidos Corporais/metabolismo , Técnicas de Cultura de Células
5.
Chemosphere ; 311(Pt 1): 136991, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36306967

RESUMO

Humans are simultaneously exposed to phenols and phthalates (PAEs). However, the mixture effect of phenols and PAEs on the body size of twins is lacking. From 2016 to 2018, we recruited 228 pregnant twins and collected up to three urine samples. A total of 8 PAE metabolites and 7 phenols were detected in urine by liquid chromatography-tandem mass spectrometry. Chemical individual and mixture effects were estimated. Multivariable linear regression results presented the percentage change in twins' growth differences at one month old with maternal PAE and phenol exposure. These chemicals were positively associated with weight differences during the entire trimester. Moreover, the quantile g-computed model showed that increased urinary concentrations of all chemicals by one quartile were associated with a 22.85% (95%CI: 11.21-35.72%), 22.60% (95%CI: 12.31-33.83%), and 24.05% (95%CI: 13.11-36.05%) larger weight difference within twins in each trimester, respectively. Increasing all PAE metabolites and phenols by one quantile across the entire trimester, weight differences increased by 26.61% (95% CI: 15.79%, 38.44%), and height differences increased by 15.84% (95%CI: 3.92%, 29.13%). Co-exposure to PAEs and phenols may primarily play a role in twins' growth.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Gravidez , Feminino , Humanos , Lactente , Fenóis/urina , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Tamanho Corporal
6.
Chemosphere ; 311(Pt 1): 137039, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36342026

RESUMO

Limited information is available on the links between heavy metals' exposure and coronary heart disease (CHD). We aim to establish an efficient and explainable machine learning (ML) model that associates heavy metals' exposure with CHD identification. Our datasets for investigating the associations between heavy metals and CHD were sourced from the US National Health and Nutrition Examination Survey (US NHANES, 2003-2018). Five ML models were established to identify CHD by heavy metals' exposure. Further, 11 discrimination characteristics were used to test the strength of the models. The optimally performing model was selected for identification. Finally, the SHapley Additive exPlanations (SHAP) tool was used for interpreting the features to visualize the selected model's decision-making capacity. In total, 12,554 participants were eligible for this study. The best performing random forest classifier (RF) based on 13 heavy metals to identify CHD was chosen (AUC: 0.827; 95%CI: 0.777-0.877; accuracy: 95.9%). SHAP values indicated that cesium (1.62), thallium (1.17), antimony (1.63), dimethylarsonic acid (0.91), barium (0.76), arsenous acid (0.79), total arsenic (0.01) in urine, and lead (3.58) and cadmium (4.66) in blood positively contributed to the model, while cobalt (-0.15), cadmium (-2.93), and uranium (-0.13) in urine negatively contributed to the model. The RF model was efficient, accurate, and robust in identifying an association between heavy metals' exposure and CHD among US NHANES 2003-2018 participants. Cesium, thallium, antimony, dimethylarsonic acid, barium, arsenous acid, and total arsenic in urine, and lead and cadmium in blood show positive relationships with CHD, while cobalt, cadmium, and uranium in urine show negative relationships with CHD.


Assuntos
Arsênio , Doença das Coronárias , Poluentes Ambientais , Metais Pesados , Urânio , Adulto , Humanos , Inquéritos Nutricionais , Cádmio/urina , Antimônio , Exposição Ambiental/análise , Bário , Tálio , Cobalto/urina , Césio , Doença das Coronárias/epidemiologia , Aprendizado de Máquina
7.
Sci Total Environ ; 856(Pt 1): 159050, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36174683

RESUMO

BACKGROUND: Evidence from in vitro and rodent studies suggests that organophosphate esters (OPEs) may disrupt sex steroid hormone homeostasis, but no human studies, to date, have examined the effects of in utero exposure to OPEs on offspring reproductive development. OBJECTIVE: Anogenital distance (AGD) is a sensitive biomarker of fetal hormonal milieu and has been used to assess reproductive toxicity. We evaluated the longitudinal effects of prenatal exposure to OPEs on the AGD of offspring from birth to 4 years. METHODS: Based on Shanghai-Minhang Birth Cohort Study, pregnant women provided urine samples at a gestational age of 12-16 weeks, which were analyzed for eight OPE metabolites. AGD was measured in offspring at birth and 0.5, 1, and 4 years of age. We used generalized estimating equations (GEE) and Bayesian kernel machine regression (BKMR) models to estimate the associations of prenatal exposure to individual OPE metabolites and OPE mixtures with AGD stratified by sex. RESULTS: A total of 733 mother-infant pairs were analyzed. Prenatal exposure to diphenyl phosphate and bis-(2-ethylhexyl) phosphate was associated with decreased AGD in boys in GEE models. Bis-(1-chloro-2-propyl) phosphate (BCIPP) showed a similar but marginally significant effect. Prenatal exposure to most OPE metabolites was associated with decreased AGD in girls, with the most profound association observed for bis (2-butoxyethyl) phosphate (BBOEP) and alkyl-OPEs. The OPE mixture was also inversely associated with AGD in both sexes. The single-exposure effects of BKMR models were largely consistent with those observed in the GEE models. In addition, alkyl-OPEs, particularly BBOEP, contributed the most to the decreased AGD in girls, while BCIPP contributed the most to the decreased AGD in boys. CONCLUSIONS: This study provides the first human evidence that prenatal exposure to OPEs is associated with decreased AGD in offspring. The magnitude of these effects may vary depending on the structure of OPEs.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Masculino , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos de Coortes , Teorema de Bayes , China , Organofosfatos/toxicidade , Organofosfatos/urina , Fosfatos
8.
Sci Total Environ ; 857(Pt 2): 159449, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36244474

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) pose significant health risks. However, no nationwide cohort has been established to consistently record biomonitoring data on PAH exposure in the Chinese population. Biomonitoring data from 56 published studies were combined in this study to develop a profile of urinary PAH metabolites among Chinese population in the 2010s. The stacked column charts described the composition profiles of hydroxylated PAHs (OH-PAHs) in general, special, and occupational populations. Hydroxynaphthalene (OH-Nap) and hydroxyfluorene (OH-Flu) accounted for more than half of the urinary OH-PAH in general and special populations. The urine of the occupational populations contained a significant amount of hydroxyphenanthrene (OH-Phe) and 1-hydroxypyrene (1-OHPyr). Furthermore, this study analyzed the distribution profiles of non-occupationally exposed populations, such as spatial distribution, age distribution, and trends over time. The population of the Southern region had higher urinary OH-PAH concentrations than the population of the Northern region. Adults (45-55 years old) had the highest level of internal PAH exposure. Between 2010 and 2018, the overall trend of urinary OH-PAHs in Chinese general populations decreased. The cumulative distribution function (CDF) revealed that 1-OHNap and 1-OHPyr were better at distinguishing internal PAH exposure among different populations. The sum of OH-Flu and OH-Phe in urine can be used to assess the impact of indoor and outdoor environments on human exposure to PAHs. Our findings suggest that more emphasis should be placed on collecting biomonitoring data for adults of all ages (particularly in the Northern region) and vulnerable populations. In conclusion, this study advocates for the establishment of a nationwide cohort study of Chinese populations as soon as possible in the future to evaluate the Chinese population's exposure to environmental contaminants.


Assuntos
Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Monitoramento Biológico , China , Biomarcadores/urina
9.
Sci Total Environ ; 855: 158788, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36116648

RESUMO

BACKGROUND/AIMS: Phthalates and their replacements are endocrine/metabolic disruptors that may impact gestational weight gain (GWG) - a pregnancy health indicator. We investigated overall and fetal sex-specific associations of individual and cumulative phthalate/replacement biomarkers with GWG. METHODS: Illinois women (n = 299) self-reported their weight pre-pregnancy and at their final obstetric appointment before delivery (median 38 weeks). We calculated pre-pregnancy body mass index and gestational age-specific GWG z-scores (GWGz). We quantified 19 phthalate/replacement metabolites (representing 10 parent compounds) in pools of up-to-five first-morning urine samples, collected approximately monthly between 8 and 40 weeks gestation. We used linear regression, quantile-based g-computation (QGComp), and weighted quantile sum regression (WQSR) to evaluate associations of ten biomarkers (individual metabolites or parent molar-sums) individually or as mixtures (in interquartile range intervals) with GWGz. We evaluated associations in all women and stratified by fetal sex. RESULTS: Individually, sums of metabolites of di(2-ethylhexyl) phthalate (Æ©DEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (Æ©DiNCH), and di(2-ethylhexyl) terephthalate (Æ©DEHTP) had consistent inverse associations with GWGz, and some associations were fetal sex-specific. When evaluating phthalates/replacements as a mixture, QGComp identified Æ©DEHP, Æ©DEHTP, and mono-(3-carboxypropyl) phthalate, along with sum of di(isononyl) phthalate metabolites (Æ©DiNP) and monobenzyl phthalate as notable contributors to lower and higher GWGz, respectively, resulting in a marginal inverse joint association in all women (ß: -0.29; 95% CI: -0.70, 0.12). In women carrying females, Æ©DEHP contributed to the marginal inverse joint association (ß: -0.54; 95% CI: -1.09, 0.03). However, there was no overall association in women carrying males (ß: 0.00; 95% CI: -0.60, 0.59), which was explained by approximately equal negative (driven by Æ©DEHTP) and positive (driven by Æ©DiNP) partial associations. WQSR analyses consistently replicated these QGComp findings. CONCLUSIONS: Biomarkers of phthalates/replacements were fetal sex-specifically associated with GWGz. Because Æ©DEHTP contributed substantively to mixture associations, additional studies in pregnant women may be needed around this plasticizer replacement.


Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Ganho de Peso na Gestação , Ácidos Ftálicos , Humanos , Masculino , Feminino , Gravidez , Exposição Ambiental/análise , Ácidos Ftálicos/urina , Plastificantes/análise , Disruptores Endócrinos/urina , Biomarcadores/urina , Poluentes Ambientais/análise
10.
Sci Total Environ ; 855: 158852, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36122707

RESUMO

BACKGROUND: Few studies have investigated the adverse effects of preconception phthalate (PAE) exposure on birth weight in couples receiving assisted reproductive technology (ART) compared to naturally conceived newborns. OBJECTIVES: We examined the association between parental preconception/prenatal urinary phthalate exposure and low birth weight (LBW) risk in couples who conceived using ART or naturally. METHODS: From the Jiangsu Birth Cohort Study (China), we recruited 544 couples who conceived after infertility treatment and 940 couples who conceived naturally and gave birth to a singleton infant between November 2014 and December 2019. Seventeen metabolites of phthalate and three metabolites of phthalate alternatives were analyzed in parental spot urine samples. Clinical data were collected from medical records. We used generalized linear models, elastic net regression, Bayesian kernel machine regression, and quantile-based g-computation to examine the individual and joint effects of parental phthalate exposure on birth weight and LBW risk ratios (RR). RESULTS: The relationship between parental phthalate exposure and birth weight was consistent between ART and natural conception. Maternal exposure to mono-ethyl phthalate and mono-carboxyisooctyl phthalate was associated with an increased risk of LBW in ART-conceived infants (RR = 1.27; 95 % confidence interval (CI): 1.03, 1.56; and RR = 1.31; 95 % CI: 1.03, 1.67, respectively). In contrast, in the spontaneously conceived infants, higher paternal prenatal concentrations of mono-benzyl phthalate and mono-carboxyisononyl phthalate were associated with a 40 % and 53 % increase in LBW risk, respectively. Exposure to PAE mixtures was associated with LBW in ART-conceived infants, with the effects primarily driven by di-ethyl phthalate, benzylbutyl phthalate, and di-isononyl phthalate metabolites. Sex-specific LBW was observed, with females appearing to be more susceptible than males. CONCLUSIONS: Maternal preconception and paternal prenatal exposure to phthalates were associated with increased risk of LBW in infants. Compared with natural conception, ART-conceived fetuses were more sensitive to PAE mixtures, which requires further attention.


Assuntos
Coorte de Nascimento , Ácidos Ftálicos , Humanos , Recém-Nascido , Gravidez , Masculino , Lactente , Feminino , Peso ao Nascer , Estudos Prospectivos , Estudos de Coortes , Teorema de Bayes , Ácidos Ftálicos/urina , Recém-Nascido de Baixo Peso , Técnicas de Reprodução Assistida
11.
Sci Total Environ ; 855: 158843, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36122716

RESUMO

Pentachlorophenol (PCP) is ubiquitous and moderately persistent in the environment, and it is an identified human carcinogen. Previous animal experiments indicate that toxic mechanisms of PCP include oxidative stress. However, no epidemiological study has reported the association between PCP exposure and oxidative stress; such association in pregnant women, a vulnerable population, is of particular interest. This study aimed to characterize PCP concentrations in 2304 urine samples from 768 pregnant women, explore its determinants, and evaluate the associations between PCP exposure and three oxidative stress biomarkers across three trimesters. The median concentrations of PCP (100% detected) in the first, second, and third trimester were 0.61, 0.59, and 0.48 ng/mL, respectively, with a significant decrease trend. The intraclass correlation coefficient of specific gravity (SG)-adjusted PCP was 0.26, indicating high variability for PCP across the three trimesters. PCP concentrations were significantly higher in older, pre-pregnancy overweight, multiparous, high-income, and employed women during pregnancy. Urinary PCP was markedly lower in samples collected during spring compared to other seasons. Linear mixed effect models for repeated measures revealed that ln-transformed SG-adjusted PCP was significantly associated with increased 8-hydroxy-2'-deoxyguanosine (8-OHdG; percent change [%Δ] caused by each interquartile range increase of PCP: 46.2, 95% confidence interval [CI]: 40.2, 52.5) and 8-hydroxyguanosine (8-OHG;%Δ [95% CI]: 44.8 [40.1, 49.8]), but the positive association with 4-hydroxy2-nonenal-mercapturic acid (HNE-MA) was not significant. PCP was also positively associated with increased 8-OHdG and 8-OHG in each trimester using general linear models, and its associations with HNE-MA were only significant at T1 (%Δ [95% CI]: 19.1 [1.05, 40.3]) and T2 (%Δ [95% CI]: 12.6 [0.32, 26.3]). Our findings provide valuable information about PCP exposure characteristics during pregnancy and the potential effects of PCP exposure on oxidative stress in pregnant women.


Assuntos
Pentaclorofenol , Humanos , Animais , Feminino , Gravidez , Idoso , Pentaclorofenol/toxicidade , Estudos Longitudinais , Gestantes , Biomarcadores/urina , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , China
12.
Environ Res ; 216(Pt 3): 114685, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341787

RESUMO

Obesity is a major threat to health, but the etiology of obesity is incompletely understood. Phthalates, synthetic chemicals ubiquitous in the environment, are suspected to have obesogenic effects, but the relationship of phthalates and obesity in humans remains uncertain. We examined whether phthalate exposure was associated with body fat gain in midlife women. We analyzed data from 1369 women in the Study of Women's Health Across the Nation Multi-Pollutant Study. Eleven phthalate metabolites measured in spot urine samples at baseline (1999/2000) were standardized with covariate-adjusted creatinine. Body weight (BW), fat mass (FM) from dual-energy X-ray absorptiometry (DXA), and body fat percentage (BF%) from DXA were measured near-annually until 2016/2017. For each metabolite, linear mixed effects models with time and log2(metabolite) interactions were examined, adjusting for demographic, lifestyle, and menopause-related factors. Analyses were conducted overall and stratified by baseline obesity status. As sensitivity analyses, all analyses were repeated using a second set of metabolites measured in 2002/2003. Higher levels of all metabolites except mono-carboxy-isononyl phthalate were associated with faster increases in BF%. Per doubling of metabolite concentrations, differences in five-year BF% change ranged from 0.03 percentage point (ppt) (95% confidence interval (CI): -0.03, 0.09) for mono-isobutyl phthalate to 0.09 ppt (95% CI: 0.02, 0.16) for mono(3-carboxypropyl) phthalate. Results were similar for FM change, but associations with BW change were mostly null. In stratified analyses by baseline obesity status, positive associations were strongest in women who were normal/underweight at baseline. When metabolites from 2002/2003 were used as exposures, most associations were attenuated and not statistically significant, but they remained positive for normal/underweight women. In conclusion, phthalate metabolites were associated with more rapid body fat gain in midlife women, but our results need confirmation given attenuation of estimates in the sensitivity analyses.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Feminino , Humanos , Poluentes Ambientais/urina , Magreza , Exposição Ambiental/análise , Ácidos Ftálicos/urina , Obesidade/induzido quimicamente , Obesidade/epidemiologia , Tecido Adiposo/metabolismo , Saúde da Mulher
13.
Environ Res ; 216(Pt 3): 114727, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36356671

RESUMO

BACKGROUND: Phthalates are endocrine-disrupting chemicals linked to a higher risk of numerous chronic health outcomes. Diet is a primary source of exposure, but prior studies exploring associations between dietary patterns and phthalate exposure are limited. OBJECTIVES: We evaluated the associations between dietary patterns and urinary phthalate biomarkers among a subset of postmenopausal women participating in the Women's Health Initiative (WHI). METHODS: We included WHI participants selected for a nested case-control study of phthalates and breast cancer (N = 1240). Dietary intake was measured via self-administered food frequency questionnaires at baseline and year-3. We used these data to calculate scores for alignment with the Dietary Approach to Stop Hypertension (DASH), alternative Mediterranean (aMed), and Dietary Inflammatory Index (DII) diets. We measured 13 phthalate metabolites and creatinine in 2-3 urine samples per participant collected over 3-years when all participants were cancer-free. We fit multivariable generalized estimating equation models to estimate the cross-sectional associations. RESULTS: DASH and aMed dietary scores were inversely associated with the sum of di(2-Ethylhexyl) phthalate (-6.48%, 95% CI -9.84, -3.00; -5.23%, 95% CI -8.73, -1.60) and DII score was positively associated (9.00%, 95% CI 5.04, 13.11). DASH and aMed scores were also inversely associated with mono benzyl phthalate and mono-3-carboxypropyl phthalate. DII scores were positively associated with mono benzyl phthalate and the sum of di-n-butyl phthalate. DISCUSSION: Higher dietary alignment with DASH and aMed dietary patterns were significantly associated with lower concentrations of certain phthalate biomarkers, while an inflammatory diet pattern was associated with higher phthalate biomarker concentrations. These findings suggest that dietary patterns high in fruits, vegetables, and low-fat foods and low in processed foods may be useful in avoiding exposure to phthalates.


Assuntos
Pós-Menopausa , Saúde da Mulher , Humanos , Feminino , Estudos de Casos e Controles , Estudos Transversais , Biomarcadores/urina
14.
Environ Res ; 216(Pt 1): 114474, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36202243

RESUMO

BACKGROUND: Phenolic compounds with potential adverse health effects are gradually being replaced. Little is known about the potential health risks of BPA, BP3, and TCS exposure in children and adolescents aged 6-19 years in the United States. OBJECTIVES: To determine trends and rates of change in hazard indices (HI) for three phenolics in U.S. children and adolescents for BPA, BP3, TCS, and to assess changes in gender, race/ethnicity, age, and potential health risks. METHODS: Metabolic biomonitoring data from field-collected urine samples from the National Health and Nutrition Examination Survey (NHANES) were utilized. Daily intake of three phenols (bisphenol A, benzophenone-3, and triclosan) between 2005 and 2016 in children and adolescents were obtained. Cumulative risk indicators, including hazard quotient (HQ), hazard index (HI), and maximum cumulative ratio (MCR), were used for the health risk assessment of the three phenols. RESULTS: During this period, the change in LSGM HI was -2.9% per cycle [95% Cl: (-3.7%, -2.2%)], and the percentage of participants with HI > 0.1 decreased from 15.6% to 10.5%. Children (6-11 years) had higher mean HI values than adolescents (12-19 years), while female had higher LSGM HI values than male. MCR values were generally low and negatively correlated with HI. However, the average value of MCR increased from 1.722 to 2.107 during this period. CONCLUSION: Exposure to phenolics among U.S. children and adolescents has changed in recent decades. However, gaps in data limit the interpretation of trends but legislative activity and advocacy campaigns by nongovernmental organizations may play a role in changing trends. Moreover, there are growing concerns about the potential health risks associated with exposure to multiple phenols in children and adolescents.


Assuntos
Poluentes Ambientais , Triclosan , Criança , Adolescente , Masculino , Feminino , Humanos , Estados Unidos , Triclosan/toxicidade , Triclosan/urina , Inquéritos Nutricionais , Poluentes Ambientais/toxicidade , Poluentes Ambientais/urina , Exposição Ambiental , Compostos Benzidrílicos/toxicidade , Compostos Benzidrílicos/urina , Fenóis/toxicidade , Fenóis/urina
15.
Environ Res ; 216(Pt 1): 114490, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36220444

RESUMO

BACKGROUND: Passive exposure to the aerosols of electronic cigarettes (e-cigarettes) has been little studied. We assessed this exposure in late pregnancy in a woman and her 3-year-old child, exposed through e-cigarette use by another household member. METHODS: This prospective longitudinal case study involved a family unit consisting of an e-cigarette user, a pregnant woman who delivered an infant during the study, and the couple's older 3-year-old son. At 31, 36, and 40 weeks of the pregnancy, we measured biomarkers (nicotine metabolites, tobacco-specific nitrosamines, propanediols, glycerol, and metals) in the urine and hair of all three participants and in the saliva of the adults, in cord blood at delivery, and in the breast milk at the postpartum period. RESULTS: Samples from the e-cigarette user showed quantifiable concentrations of all analytes assessed (maximum urinary cotinine concentration, 4.9 ng/mL). Among samples taken from the mother, nicotine and its metabolites were found mainly in urine and also in saliva and hair, but not in cord blood. During the postpartum period, we found cotinine concentrations of 2.2 ng/mL in the mother's urine and 0.22 ng/mL in breast milk; 1,2-propanediol was generally detected in urine and saliva, but not in cord blood or breast milk. The maximum urinary cotinine concentration in the 3-year-old child was 2.6 ng/mL and propanediols also were detected in his urine. Nitrosamines were not detected in samples taken from the mother or the 3-year-old. Metals found in the refill liquid were detected at low levels in both the mother and the 3-year-old. CONCLUSIONS: We detected low but not negligible concentrations of e-cigarette-related analytes (including cord blood and breast milk) in an exposed pregnant non-user and in a 3-year-old child also living in the home. Passive exposure to e-cigarette aerosols cannot be disregarded and should be assessed in larger observational studies.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nitrosaminas , Poluição por Fumaça de Tabaco , Humanos , Adulto , Feminino , Gravidez , Pré-Escolar , Cotinina/urina , Nicotina/análise , Estudos Prospectivos , Poluição por Fumaça de Tabaco/análise , Aerossóis , Biomarcadores/urina , Metais , Propilenoglicóis
16.
Sci Total Environ ; 857(Pt 1): 159322, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36220473

RESUMO

BACKGROUND: Few studies have examined whether gestational exposure to organophosphate esters (OPEs), widely used chemicals with potential endocrine-disrupting potency and developmental toxicity, is associated with impaired infant growth. METHODS: We analyzed data from 329 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006, Cincinnati, Ohio, USA). We quantified concentrations of four OPE metabolites in maternal urine collected at 16 and 26 weeks of gestation, and at delivery. We calculated z-scores using 2006 World Health Organization (WHO) child growth standards for the 4-week anthropometric measures (weight, length, and head circumference), the ponderal index, and weekly growth rates. We used multiple informant models to examine window-specific associations between individual OPE metabolites and anthropometric outcomes. We further modeled OPEs as a mixture for window-specific associations with 4-week anthropometric outcomes using mean field variational Bayesian inference procedure for lagged kernel machine regression (MFVB-LKMR). We stratified the models by infant sex. RESULTS: Diphenyl phosphate (DPHP) in mothers at 16 weeks, and bis(2-chloroethyl) phosphate (BCEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) at delivery were positively associated with z-scores of weight, length, and head circumference in all infants at 4 weeks of age. After stratifying by infant sex, positive associations were only observed in males for DPHP at 16 weeks and BCEP at delivery and in females for BDCIPP at delivery. Negative associations not present in all infants were observed in males for di-n-butyl phosphate (DNBP) at 26 weeks of gestation with weight z-score and DPHP at delivery with head circumference z-score. Results were generally similar using MFVB-LKMR models with more conservative 95 % credible intervals. We did not identify consistent associations of gestational OPE metabolite concentrations with the ponderal index and weekly growth rates. CONCLUSION: In this cohort, exposure to OPEs during gestation was associated with altered infant anthropometry at 4 weeks after birth.


Assuntos
Ésteres , Retardadores de Chama , Criança , Lactente , Masculino , Feminino , Humanos , Teorema de Bayes , Ésteres/urina , Organofosfatos/metabolismo , Antropometria , Fosfatos , Retardadores de Chama/metabolismo
17.
Environ Res ; 216(Pt 1): 114320, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36100102

RESUMO

Passive smoking is a preventable and significant cause of many serious health problems, with children being particularly at risk. In the fifth German Environmental Survey (GerES V), conducted from 2014 to 2017, information reflecting the extent of passive smoke exposure in children and adolescents was collected by interview-based questionnaires and human biomonitoring (HBM) analyses of cotinine in urine from 2260 participants, aged 3-17 years. Based on these population-representative data, we describe current passive smoke exposure stratified by different subgroups and identify specific exposure determinants using multivariate logistic regression. The questionnaire data revealed that 42% of children and adolescents lived with at least one smoker in the household. Quantifiable concentrations of cotinine could be detected in 56% of the participants. The overall median concentration of cotinine was 0.2 µg/L, with children and adolescents of low socioeconomic status found to be a group particularly affected by passive smoke with higher cotinine concentrations (median = 1.2 µg/L). In the multiple analysis, the most significant predictor of cotinine levels derived from the questionnaire was passive smoking at home (odds ratio (OR) 13.07 [95CI: 4.65, 36.70]). However, parental smoking and passive smoking among friends and relatives could also be identified as independent factors influencing elevated cotinine levels. The comparison between the previous cycle GerES IV (2003-2006) on 3-14-year-olds and GerES V shows that tobacco smoke exposure of children decreased significantly. This decrease is likely an effect of extensive non-smoker protection laws being enforced 2007-2008 on federal and state level. This is reflected by a halving of urinary cotinine concentrations. Nevertheless, our results indicate that passive smoke is still a relevant source of harmful pollutants for many children and adolescents in Germany, and thus support the need for further efforts to reduce passive smoke exposure, especially in the private environment.


Assuntos
Cotinina , Poluição por Fumaça de Tabaco , Criança , Humanos , Adolescente , Cotinina/urina , Poluição por Fumaça de Tabaco/análise , Monitoramento Biológico , Alemanha , Inquéritos e Questionários , Fumar , Exposição Ambiental
18.
Environ Res ; 216(Pt 2): 114576, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36252832

RESUMO

Midlife in women is an understudied time for environmental chemical exposures and menopausal outcomes. Recent cross-sectional research links phthalates with hot flashes, but little is known regarding such associations over time. Our objective was to estimate longitudinal associations between repeated measures of urinary phthalate metabolite concentrations and hot flash outcomes in midlife women. Using data from the Midlife Women's Health Study (MWHS), a prospective longitudinal study, we fit generalized linear mixed-effects models (GLMMs) and Cox proportional hazards regression models to repeated measures over a 4-year period. Recruitment occurred in Baltimore and surrounding counties, Maryland, USA between 2006 and 2015. Participants were premenopausal/perimenopausal women (n = 744) aged 45-54 years, who were not pregnant, not taking menopausal symptom medication or oral contraceptives, did not have hysterectomy/oophorectomy, and irrespective of hot flash experience. Baseline mean (SD) age was 48.4 (2.45), and 65% were premenopausal. Main outcome measures included adjusted odds ratios (ORs) for 4 self-reported hot flash outcomes (ever experienced, past 30 days experience, weekly/daily, and moderate/severe), and hazard ratios (HRs) for incident hot flashes. We observed mostly increased odds of certain hot flash outcomes with higher concentrations of metabolites of di (2-ethylhexyl) phthalate (DEHP), monoisobutyl phthalate (MiBP), and a molar summary measure of plasticizer phthalate metabolites (DEHP metabolites, mono-(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP)). Some associations between exposures and outcomes indicated decreased odds. In conclusion, phthalate metabolites were associated with certain hot flash outcomes in midlife women. Midlife may be a sensitive period for higher phthalate metabolite concentrations with respect to menopausal symptoms.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Feminino , Humanos , Gravidez , Fogachos/epidemiologia , Poluentes Ambientais/urina , Estudos Prospectivos , Estudos Transversais , Estudos Longitudinais , Ácidos Ftálicos/urina , Exposição Ambiental , Saúde da Mulher
19.
Environ Res ; 216(Pt 2): 114638, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306878

RESUMO

Starting in 2002, regulations and legislative amendments in Germany focused on the non-smoker protection with several measures to reduce exposure to secondhand tobacco smoke (SHS). The present work aimed to evaluate the relationship between polycyclic aromatic hydrocarbons (PAHs) and SHS exposure and to determine to which extent enforced non-smoking regulations and smoking bans affected the exposure of the non-smoking population in Germany since their implementation in the early 2000s until today. For this purpose, cotinine and selected monohydroxylated PAHs (OH-PAHs) were analyzed by means of (UP)LC-MS/MS in 510 24-h-urine samples of the Environmental Specimen Bank collected over a time span of 24 years from 1995 to 2019. Median urinary cotinine levels were found to steadily and significantly decline by 82% from 1995 to 2019. A significant decrease of urinary 3-hydroxybenzo[a]pyrene (19%), 1-OH-pyrene (39%), 1-naphthol (66%), 1- (17%), 2- (25%), and 3-OH-phenanthrene (22%) was also observed throughout the same time span. The decline in urinary levels of cotinine and several OH-PAHs can most likely be attributed to smoking bans and regulations limiting SHS and PAH exposure. This study therefore emphasizes the relevance of human biomonitoring to investigate the exposure of humans to chemicals of concern, assess the effectiveness of regulatory measures, and help policies to enforce provisions to protect public health.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluição por Fumaça de Tabaco , Humanos , Hidrocarbonetos Policíclicos Aromáticos/urina , Cotinina/urina , Poluição por Fumaça de Tabaco/análise , Cromatografia Líquida , Monitoramento Ambiental , Espectrometria de Massas em Tandem , Pirenos , Alemanha , Biomarcadores/urina
20.
BMC Vet Res ; 18(1): 389, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333744

RESUMO

BACKGROUND: In humans, kidney injury molecule-1 (KIM-1) is a biomarker of acute kidney injury that can be quantified in urine. Preliminary investigation in cats with experimentally induced acute kidney injury showed that KIM-1 urine concentration correlated with kidney injury histopathology scores. A lateral flow assay (LFA) has recently become available for patient-side feline KIM-1 measurement. In vitro parameters of the assay have not yet been determined. The objectives of this study were to determine detection of KIM-1 in urine stored at different temperatures over time, to establish the linear range of the LFA, and to assess the intra-assay repeatability of measurements.  RESULTS: Ten urine samples with a range of KIM-1 concentrations were stored at room temperature (22o C), 4o C or -20o C, and tested with the LFA on days 0, 1, 2, 3, 7, 14, and 30. The concentration of KIM-1 in samples was not significantly different from the day 0 value, except one sample that had been stored for 30 days at room temperature yielded a significantly higher value. The assay results had a correlation coefficient of 0.922. The mean coefficient of variation for all samples was 15.7%. The slope of the curve of expected versus measured values in samples diluted two-fold nine times was 0.908, and results were linear over all dilutions. CONCLUSIONS: The LFA for feline KIM-1 yields consistent results from stored urine samples. These characteristics will allow for KIM-1 to be measured retrospectively if immediate testing is not feasible. Within assay precision was high, and linearity over 9 logs of dilution suggests suitability for a range of subclinical and clinical kidney injuries.


Assuntos
Injúria Renal Aguda , Doenças do Gato , Gatos , Animais , Humanos , Temperatura , Estudos Retrospectivos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/veterinária , Injúria Renal Aguda/urina , Rim , Biomarcadores/urina
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