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1.
Environ Pollut ; 347: 123690, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38452837

RESUMO

As novel contaminants, short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) have been of great concern in the past several years. Shanghai was one of the provinces with the largest chlorinated paraffins (CPs) emission in China; nevertheless, there is currently little information on the human exposure to SCCPs and MCCPs, particularly MCCPs. In this study, 25 breast milk samples were collected in Shanghai from 2016 to 2017. The concentrations of SCCPs and MCCPs were determined using two-dimensional gas chromatography coupled with orbitrap high-resolution mass spectrometry (GC × GC-orbitrap-HRMS) to investigate their characteristics and assess the associated health risks for breast-fed infants. Compared with the previous studies in other areas, the current study presented the higher CPs concentrations, with median concentrations of SCCPs and MCCPs up to 771 and 125 ng/g lipid weight (lw), respectively. The exposure profiles of the CPs were characterized by C10 and Cl6-7 as the predominant congeners of SCCPs, while C14 and Cl7-9 were identified as the dominant groups of MCCPs. CP-42 and CP-52 were identified as potential sources of CPs found in breast milk samples collected in Shanghai. The concentrations of MCCPs exhibited a positive correlation (p value < 0.05) with the dietary consumption of meat and poultry. No significant positive correlations were observed for SCCPs and MCCPs with polychlorinated dibenzodioxins/furans (PCDD/Fs) congeners. A preliminary exposure assessment showed that SCCPs in breast milk potentially posed high risks to the breast-fed infants in Shanghai.


Assuntos
Hidrocarbonetos Clorados , Dibenzodioxinas Policloradas , Lactente , Feminino , Humanos , China , Leite Humano/química , Parafina/análise , Hidrocarbonetos Clorados/análise , Dibenzofuranos/análise , Monitoramento Ambiental/métodos , Dibenzodioxinas Policloradas/análise , Medição de Risco
2.
Clin Respir J ; 18(3): e13741, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38450981

RESUMO

Histiocytic sarcoma is an aggressive haematopoietic malignancy accounting for less than 1% of haematolymphoid neoplasms with a diagnosis based on morphology and immunophenotype of tissue biopsies with a very poor prognosis. Here, we report a 45-year-old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Tests demonstrated that TMB was 21 Muts/Mb PD-L1 expression was 90% positive, and the disease has been well-controlled over 3 years using immune checkpoint inhibitors (nivolumab and pembrolizumab). Bioinformatic pan-cancer analysis verified that there was the highest genetic alteration frequency of PD-L1 in which amplification accounted for the majority of sarcoma tumour samples. Following that, we found that the genetic alteration of PD-L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10-4 ), progress-free survival (PFS) (p = 4.90 × 10-2 ) and disease-specific survival (DSS) (p = 4.90 × 10-2 ). To our knowledge, this may be the first reported case with high PD-L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely.


Assuntos
Sarcoma Histiocítico , Neoplasias Pulmonares , Sarcoma , Masculino , Humanos , Pessoa de Meia-Idade , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/genética , Antígeno B7-H1/genética , Nivolumabe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Imunoterapia , Biologia Computacional
3.
Environ Sci Technol ; 58(10): 4737-4750, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38408453

RESUMO

Landfills are the final stage of urban wastes containing perfluoroalkyl and polyfluoroalkyl substances (PFASs). PFASs in the landfill leachate may contaminate the surrounding groundwater. As major environmental pollutants, emerging PFASs have raised global concern. Besides the widely reported legacy PFASs, the distribution and potential toxic effects of numerous emerging PFASs remain unclear, and unknown PFASs still need discovery and characterization. This study proposed a comprehensive method for PFAS screening in leachate samples using suspect and nontarget analysis. A total of 48 PFASs from 10 classes were identified; nine novel PFASs including eight chloroperfluoropolyether carboxylates (Cl-PFPECAs) and bistriflimide (HNTf2) were reported for the first time in the leachate, where Cl-PFPECA-3,1 and Cl-PFPECA-2,2 were first reported in environmental media. Optimized molecular docking models were established for prioritizing the PFASs with potential activity against peroxisome proliferator-activated receptor α and estrogen receptor α. Our results indicated that several emerging PFASs of N-methyl perfluoroalkyl sulfonamido acetic acids (N-MeFASAAs), n:3 fluorotelomer carboxylic acid (n:3 FTCA), and n:2 fluorotelomer sulfonate (n:2 FTSA) have potential health risks that cannot be ignored.


Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Simulação de Acoplamento Molecular , Fluorocarbonos/toxicidade , Fluorocarbonos/análise , Instalações de Eliminação de Resíduos , Alcanossulfonatos , Ácidos Carboxílicos/análise
4.
PeerJ Comput Sci ; 9: e1467, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547422

RESUMO

Semantic segmentation for extracting buildings and roads from uncrewed aerial vehicle (UAV) remote sensing images by deep learning becomes a more efficient and convenient method than traditional manual segmentation in surveying and mapping fields. In order to make the model lightweight and improve the model accuracy, a lightweight network using object attention (LOANet) for buildings and roads from UAV aerial remote sensing images is proposed. The proposed network adopts an encoder-decoder architecture in which a lightweight densely connected network (LDCNet) is developed as the encoder. In the decoder part, the dual multi-scale context modules which consist of the atrous spatial pyramid pooling module (ASPP) and the object attention module (OAM) are designed to capture more context information from feature maps of UAV remote sensing images. Between ASPP and OAM, a feature pyramid network (FPN) module is used to fuse multi-scale features extracted from ASPP. A private dataset of remote sensing images taken by UAV which contains 2431 training sets, 945 validation sets, and 475 test sets is constructed. The proposed basic model performs well on this dataset, with only 1.4M parameters and 5.48G floating point operations (FLOPs), achieving excellent mean Intersection-over-Union (mIoU). Further experiments on the publicly available LoveDA and CITY-OSM datasets have been conducted to further validate the effectiveness of the proposed basic and large model, and outstanding mIoU results have been achieved. All codes are available on https://github.com/GtLinyer/LOANet.

5.
Clin Lab ; 69(4)2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37057949

RESUMO

BACKGROUND: Hypercalcemia is a relatively common clinical problem. However, the differential diagnosis between hypercalcemia combined with hyperparathyroidism and a malignant tumor is difficult. METHODS: Appropriate laboratory tests, ultrasound and static imaging of the parathyroid, electronic gastroscopy, and histological examinations were used. RESULTS: The patient was found to have primary hyperparathyroidism due to hypercalcemia, with a parathyroid adenoma visible on color Doppler ultrasound and PET. The hypercalcemia was corrected after surgical resection. As the symptoms of nausea and vomiting did not improve, further investigations were undertaken, and gastric cancer was found on gastroscopy. CONCLUSIONS: Both primary hyperparathyroidism and gastric tumors may present with symptoms of nausea and vomiting. Clinically, multiple disease possibilities should be considered to explain a particular symptom.


Assuntos
Hipercalcemia , Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Neoplasias Gástricas , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/cirurgia , Vômito/etiologia , Náusea
6.
Chemosphere ; 313: 137587, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36535498

RESUMO

BACKGROUND: Prenatal perfluoroalkyl substances (PFAS) exposure has been reported to affect offspring neurodevelopment, while epidemiological evidences were limited and inconsistent. OBJECTIVES: We aimed to evaluate the associations between cord serum PFAS concentrations and neurodevelopment in toddlers from 1 to 3 years of age. METHODS: A total of 716 children from Sheyang Mini Birth Cohort Study (SMBCS) were included in this study. 12 PFAS concentrations were quantified in cord serum. Neurodevelopment was assessed using the Developmental Screen Test for Children Aged 0-6 Years at 1 year and the Gesell Developmental Schedules (GDS) at 2 and 3 years, respectively. Development quotient (DQ) z-score was standardized from DQ to eliminate the difference caused by two methods. We used generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) to explore the associations of single or mixture PFAS exposure with neurodevelopment measurements at each time point. Associations between PFAS exposure and longitudinal changes in DQ z-score were investigated through generalized estimating equation (GEE) and trajectory analysis. RESULTS: In general, prenatal PFAS concentrations showed negative associations with neurodevelopment measurements at specific age. When accounting for longitudinal changes from 1 to 3 years of age, PFOA was negatively associated with DQ z-score (ß = -0.212, 95% CI: -0.422, -0.003), the association was only found significant in boys after stratified by gender (ß = -0.327, 95% CI: -0.616, -0.038). Meanwhile, increased PFBS (OR = 2.159, 95% CI: 1.177, 3.959) and PFHpA (OR = 1.700, 95% CI: 1.016, 2.846) exposure was associated with elevated odds for the low-score trajectory group. The results of mixture of PFAS further confirmed above findings. CONCLUSIONS: Our findings suggested that prenatal PFAS exposure may be associated with adverse neurodevelopment effects in the first 3 years of life. Further studies are warranted to confirm our findings.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Masculino , Gravidez , Feminino , Humanos , Pré-Escolar , Lactente , Estudos de Coortes , Poluentes Ambientais/toxicidade , Teorema de Bayes , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Fluorocarbonos/toxicidade
7.
Environ Sci Technol ; 56(22): 15912-15919, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36301106

RESUMO

Human hair, as an emerging biological monitoring matrix, has begun to be used in various human exposure studies, but little research has been done on persistent organic pollutants (POPs), especially for the body burden of POPs in infants. In this study, 36 breast-fed infants in Shanghai were recruited for a study to determine their exposure to POPs, including 12 dioxin-like polychlorinated biphenyls (dl-PCBs), 6 indicator PCBs, and 8 polybrominated diphenyl ethers (PBDEs) in the inner layer (internal) and outer layer (external) of infant hair and human milk. The similarity or difference of the POP distribution pattern or concentration among these matrices was investigated, and only weak correlations (r < 0.4) were observed between the POP concentration in human milk and infant hair (internal or external). POPs in human milk have a different profile than those in infant hair, while they have stable concentration ratios (0.58-2.72), similar distribution patterns, fine Spearman's rank correlations, and tangled principal component analysis (PCA) plots in each POP family between external and internal hair samples. The result suggested that POPs in internal hair can be easily affected by those in external hair, but POPs in human milk seem to have little contribution to the POP profile in internal hair. Although infant hair cannot reflect the POPs from diet or from body burden, it can be an ideal biomatrix that estimates infant exposure to POPs from exogenous sources like house dust when considering the similar pattern of POPs and their proper accumulation period in hair.


Assuntos
Poluentes Ambientais , Bifenilos Policlorados , Lactente , Humanos , Bifenilos Policlorados/análise , Éteres Difenil Halogenados/análise , Leite Humano/química , Monitoramento Ambiental , China , Poluentes Ambientais/análise , Cabelo/química
8.
Food Chem ; 383: 132431, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35180605

RESUMO

Herbal teas have potential health benefits, but they also contain a variety of pesticides and pesticide transformation products (PTPs) that might brings health risks. Our study maps the pesticides and PTPs in two herbal teas (chrysanthemum and Lusterleaf Holly) from two main producing areas in China. Almost all 122 samples contain pesticides, with concentration ranging from 0.0005 to 10.305 mg/kg. Nearly 40% carbendazim and imidacloprid in chrysanthemum teas and λ-cyhalothrin in Lusterleaf Holly have higher concentration levels than the values permitted in EC Regulation No. 396/2005. Distinct distributions of pesticides were found in different teas and production areas. Eight PTPs were identified along with their parents, and were confirmed using a biosynthetic strategy. Acute, chronic and cumulative health risk assessments of pesticides revealed acceptable results. Our study uncovers the profile of pesticides in herbal teas, and provides new insight into discovering the potential environmental pollution and food contaminants.


Assuntos
Chrysanthemum , Resíduos de Praguicidas , Praguicidas , Chás de Ervas , China , Resíduos de Praguicidas/análise , Praguicidas/análise , Medição de Risco , Chás de Ervas/análise
9.
Chemosphere ; 271: 129447, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33476874

RESUMO

Computational QSAR models have gradually been preferred for retention time prediction in data mining of emerging environmental contaminants using liquid chromatography coupled with mass spectrometry. Generally, the model performance relies on the components such as machine learning algorithms, chemical features, and example data. In this study, we evaluated the performances of four algorithms on three feature sets, using 321 and 77 pesticides as the training and validation sets, respectively. The results were varied with different combinations of algorithms on distinct feature sets. Two strategies including enhancing the complexity of chemical features and enlarging the size of the training set were proved to improve the results. XGBoost, Random Forest, and lightGBM algorithms exhibited the best results when built on a large-scale chemical descriptors, while the Keras algorithm preferred fingerprints. These four models have comparable prediction accuracies that at least 90% of pesticides in validation set can be successfully predicted with ΔRT <1.0 min. Meanwhile, a blended prediction strategy using average results from four models presented a better result than any single model. This strategy was used for assisting identification of pesticides and pesticide transformation products in 120 strawberry samples from a national survey of food contamination. Twenty pesticides and twelve pesticide transformation products were tentatively identified, where all pesticides and two pesticide transformation products (bifenazate diazene and spirotetramat-enol) were confirmed by standard materials. The outcome of this study suggested that retention time prediction is a valuable approach in compound identification when integrated with in silico MS2 spectra and other MS identification strategies.


Assuntos
Praguicidas , Cromatografia Líquida , Contaminação de Alimentos/análise , Aprendizado de Máquina , Espectrometria de Massas , Praguicidas/análise
11.
Environ Pollut ; 268(Pt A): 115121, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33139099

RESUMO

Polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs), as the secondary environmental pollutants of the widely used brominated flame retardants (BFRs), possess the similar physicochemical and toxic properties as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). However, studies on human body exposure to them are extremely limited. In this study, forty human milk samples collected in Shanghai were measured for 13 PBDD/F congeners using gas chromatography-high resolution mass spectrometry (GC-HRMS), to investigate their exposure level and characteristics, potential source and corresponding health risks to breastfed infants. The results showed no PBDDs but three PBDF congeners including 2,3,7,8-TBDF, 1,2,3,4,6,7,8-HpBDF and OBDF (mean concentration (detection rates) are 3.2 pg/g (72.5%), 9.5 pg/g (100%) and 28 pg/g (67.5%), respectively) were detected. The average toxic equivalent quantity (TEQ, 0.42 pg/g lw) presented the highest concentration level compared to other regions reported. The contribution of PBDFs to the total TEQ of PBDD/Fs and PCDD/Fs is 6.8%. The correlation between PBDD/Fs and age or dietary habits was not observed, which normally existed in their chlorinated analogues-PCDD/Fs. Significant correlations were observed between PBDFs and highly brominated polybrominated diphenyl ethers (PBDEs) (especially for BDE 183 and BDE 209). The correlation between PCDD/Fs and PBDFs was not observed except 2,3,7,8-TBDF. The high PBDFs exposure in Shanghai may originate from the emission of PBDEs and/or non-PBDE BFRs in environment, according to the consistency of the environmental data previously reported. The average estimated dietary intakes (EDI) for breastfed infants is 2.0 pg TEQ/kg·bw/day (0.13-13 pg TEQ/kg·bw/day), within the range of the tolerable daily intake (TDI) for TCDD (1-4 pg TEQ/kg·bw/day) suggested by the World Health Organization (WHO). However, given the high toxicity of PBDD/Fs, the potential health risks of these pollutants for breastfed infants should be of concern.


Assuntos
Dioxinas , Retardadores de Chama , Dibenzodioxinas Policloradas , China , Dibenzofuranos/análise , Dibenzofuranos Policlorados , Dioxinas/análise , Retardadores de Chama/análise , Humanos , Leite Humano/química , Dibenzodioxinas Policloradas/análise , Medição de Risco
12.
Food Chem ; 320: 126576, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32200175

RESUMO

A rapid and high-throughput method using both GC-MS/MS and UPLC-Q-Orbitrap systems was applied for pesticide multi-residues analysis in food samples. Strategies based on QuEChERs extraction, intelligent data mining tools with in-house/online database, and in-silico fragment prediction system were introduced to screen and identify target/untargeted features. Full-scan combined with data-independent-acquisition modes was evaluated in real sample in an attempt to improve and facilitate the pesticide screening process, of which the results showed that FS-vDIA provided equal detection rate (100%) and far less false positive results than FS-AIF did. The proposed methodology was evaluated in analysis of pesticide multi-residues in several proficiency test samples provided by EURL, and exhibited a high detection rate (>90%) of various pesticide residues with satisfactory recoveries (70-130%) without reporting false positive results. The method was also applied in China's national surveys from 2016 to 2019, and results showed its high performance in pesticide analysis in different food matrices.


Assuntos
Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , Cromatografia Gasosa/métodos , Cromatografia Líquida de Alta Pressão/métodos , Simulação por Computador , Frutas/química , Espectrometria de Massas em Tandem/métodos , Verduras/química
13.
Wei Sheng Yan Jiu ; 47(6): 924-928, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30593321

RESUMO

OBJECTIVE: To investigate the pollution level of dioxin-like compounds in animal-derived foods from 10 cities of Shaanxi Province. METHODS: Collect four representative food samples( pork, beef, fish and eggs) to determine the concentrations of29 types of dioxin-like compounds by high-resolution gas chromatographs/high-resolution mass spectrometers( HRGC-HRMS). RESULTS: The result showed that the toxic equivalent quantity( TEQ) value of dioxin-like compounds in fish was 0. 085 pg TEQ/g, which was the biggest among the 4 food samples. The TEQ values for pork, beef and eggs were 0. 049, 0. 034 and 0. 040 pg TEQ/g, respectively. The TEQ values of dioxin-like compounds were higher in the fish meat of Ankang and the pork of Hanzhoung, but were lower than the max limit of commission regulation European Union. The total dietary intake of the above four foods was 2. 01 pg/( kg·BW·month), which was much lower than the provisional tolerable monthly intake( PTMI) of Joint FAO/WHO Expert Committee on Food Additives 70 pg/( kg·BW·month). CONCLUSION: The residents in the 10 cities of Shaanxi Province are at a low health risk caused by the intake of dioxin-like compounds.


Assuntos
Dioxinas , Ovos , Contaminação de Alimentos , Carne , Bifenilos Policlorados , Animais , Benzofuranos , Bovinos , China , Dioxinas/análise , Poluentes Ambientais , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas
14.
Anal Bioanal Chem ; 409(22): 5307-5317, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28741109

RESUMO

Commonly, analytical methods measuring brominated flame retardants (BFRs) of different chemical polarities in human serum are labor consuming and tedious. Our study used acidified diatomaceous earth as solid-phase extraction (SPE) adsorbent and defatting material to simultaneously determine the most abundant BFRs and their metabolites with different polarities in human serum samples. The analytes include three types of commercial BFRs, tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD) isomers, and polybrominated biphenyl ethers (PBDEs), and dominant hydroxylated BDE (OH-PBDE) and methoxylated BDE (MeO-PBDE) metabolites of PBDEs. The sample eluents were sequentially analyzed for PBDEs and MeO-BDEs on online gel permeation chromatography/gas chromatography-electron capture-negative ionization mass spectrometry (online GPC GC-ECNI-MS) and for TBBPA, HBCD, and OH-BDEs on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Method recoveries were 67-134% with a relative standard deviation (RSD) of less than 20%. Method detection limits (MDLs) were 0.30-4.20 pg/mL fresh weight (f.w.) for all analytes, except for BDE-209 of 16 pg/mL f.w. The methodology was also applied in a pilot study, which analyzed ten real samples from healthy donors in China, and the majority of target analytes were detected with a detection rate of more than 80%. To our knowledge, it is the first time for us in effectively determining BFRs of most types in one aliquot of human serum samples. This new analytical method is more specific, sensitive, accurate, and time saving for routine biomonitoring of these BFRs and for integrated assessment of health risk of BFR exposure.


Assuntos
Análise Química do Sangue/métodos , Retardadores de Chama/análise , Éteres Difenil Halogenados/sangue , Compostos de Bromo/análise , Éteres Difenil Halogenados/metabolismo , Humanos , Limite de Detecção , Controle de Qualidade , Extração em Fase Sólida , Fatores de Tempo
15.
Anal Bioanal Chem ; 408(18): 4897-906, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27178547

RESUMO

An improved method based on tandem solid phase extraction (SPE) cleanup and gas chromatography-high resolution mass spectrometry (GC-HRMS) has been validated for a rapid determination of dibenzo-p-dioxins/furans (PCDD/Fs), dioxin-like polychlorinated biphenyls (PCBs), marker polychlorinated biphenyls (M-PCBs), and polybrominated diphenyl ethers (PBDEs) using a large volume (50 mL) of human milk. This method was well validated for the measurement of these analytes in human milk from the general population with low limits of detection (LODs, 0.004-0.12 ng/g lipid), satisfactory accuracy (75-120 % of recoveries), and precision [less than 10 % of relative standard deviations (RSDs)]. To comprehensively evaluate the performance of this method, a good, presently validated and routinely used method based on an automated sample clean-up system (ASCS, based on the commercial acid multilayer silica, basic alumina, and carbon columns) was used in parallel for comparison. Compared with the ASCS method, this method presented comparable specificity. Additionally, this method, in contrast to ASCS method, highly reduced consumption of solvents (40 mL versus 500 mL), which results in much lower background in the procedural blank, reduced time, and enhanced sample pretreatment throughput. This method was also applied in a pilot study to measure a batch of human milk samples with satisfactory results. Graphical Abstract Characteristics of the application of tandem SPE cleanup for determination of PCDD/Fs, DL-PCBs,M-PCBs and PBDEs in human milk.


Assuntos
Poluentes Ambientais/análise , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Hidrocarbonetos Aromáticos/análise , Leite/química , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Humanos , Hidrocarbonetos Aromáticos/química , Bifenilos Policlorados , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Manejo de Espécimes/métodos
16.
Artigo em Inglês | MEDLINE | ID: mdl-27085014

RESUMO

Bromophenols (BrPs), as the metabolites of PBDEs, would be the potential exposure markers for human biomonitoring (HB) of PBDEs in urine. An analytical method using solid-phrase extraction (SPE) and gas chromatography coupled to tandem mass spectrometer (GC-MS/MS) was developed and validated for simultaneous determination of nineteen BrPs in human urine. The method detection limits (MDLs) were below 23pgmL(-1), with recovery ranged from 63% to 133% and inter-day repeatability ranged from 3% to 11% for the majority of target analytes. This method was applied in a pilot study and 2-Bromophenol (2-BrP), 4-Bromophenol (4-BrP), 2,4-Dibromophenol (2,4-DBP) and 2,4,6-Tribromophenol (2,4,6-TBP) as the predominant analytes were detected in human urine samples collected from the general population. Among the four detected analytes, 2-BrP and 4-BrP as the mono-brominated BrP congeners were firstly reported. To our knowledge, it is the first study covering all BrP congeners (from mono-brominated to penta-brominated, totally 19 congeners) in human urine. Therefore, this study is very useful for profiling urinary BrPs and discovering potential relationship between urinary BrPs and human internal exposure to PBDEs. The mechanism of fragmentation pathway of silanized BrPs was firstly illustrated in this study.


Assuntos
Biomarcadores/urina , Exposição Ambiental/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Éteres Difenil Halogenados/urina , Fenóis/urina , Espectrometria de Massas em Tandem/métodos , Biomarcadores/química , Éteres Difenil Halogenados/química , Humanos , Limite de Detecção , Modelos Lineares , Fenóis/química , Reprodutibilidade dos Testes
17.
J Chromatogr A ; 1445: 80-92, 2016 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-27063369

RESUMO

It is of great interest to develop strategic methods to enable chemicals' metabolites to be accurately and rapidly screened and identified. To screen and identify a category of metabolites with distinct isotopic distribution, this study proposed a generic strategy using in silico metabolite prediction plus accurate-mass-based isotopic pattern recognition (AMBIPR) and library identification on the data acquired via the data dependent MS/MS scan of LC-Q Exactive Orbitrap mass spectrometry. The proposed method was evaluated by the analysis of flurochloridone (FLC) metabolites in rat urine sample collected from toxicity tests. Different from the traditional isotopic pattern recognition (IPR) approach, AMBIPR here was performed based on the potential metabolites predicted via in silico metabolite prediction tools. Thus, the AMBIPR treated FLC data was only associated with FLC metabolites, consequently not only avoiding great efforts made to remove FLC-unrelated information and reveal FLC metabolites, but also increasing the percent of positive hits. Among the FLC metabolite peaks screened using AMBIPR, 87% of them (corresponding 97 metabolites and 49 biotransformation) were successfully identified via multiple MS identification techniques packaged in an established FLC's metabolites library based on Mass Frontier. Noteworthy, 34 metabolites (89%) were identified without distinct naturally isotopic distribution. The universal strategic approach based on background subtraction (BS) and mass defect filtering (MDF) was used to evaluate the AMBIPR and no more false positive and negative metabolites were detected. Furthermore, our results revealed that AMBIPR is very effective, inherently sensitive and accurate, and is easily automated for the rapidly screening and profiling chemicals related metabolites.


Assuntos
Cromatografia Líquida , Pirrolidinonas/química , Pirrolidinonas/urina , Espectrometria de Massas em Tandem , Urinálise/métodos , Animais , Biotransformação , Masculino , Pirrolidinonas/metabolismo , Ratos
18.
Can J Physiol Pharmacol ; 94(1): 28-34, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26394869

RESUMO

Rosiglitazone, which is mainly used in the treatment of diabetes mellitus, is also involved in the regulation of inflammation. The peroxisome proliferator-activated receptor (PPAR)-γ receptor subtype appears to play a pivotal role in the regulation of inflammation. However, the exact mechanism for the protective effects of rosiglitazone against inflammation such as liver injury remains unclear. The aim of this study was to investigate the effects of rosiglitazone on inflammation in the liver of rats treated with D-GaIN/LPS. Male Sprague-Dawley rats were injected with D-GaIN/LPS with or without pre-administration of rosiglitazone (3, 10, or 30 mg/kg, intraperitoneal injection). Our data showed that rosiglitazone significantly inhibited D-GaIN/LPS-induced hepatotoxicity in a dose-dependent manner, as indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Western blot analysis showed that rosiglitazone significantly decreased protein expression levels of COX-2 and production of pro-inflammatory markers, including TNF-α and IL-6, in D-GaIN/LPS-treated rat liver. The results indicated that the inhibition of D-GaIN/LPS-induced inflammation by rosiglitazone can be attributed, at least partially, to its capacity to regulate the the immunoregulatory transcription factor nuclear factor kappa B (NF-κB) signaling pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , NF-kappa B/metabolismo , Tiazolidinedionas/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Masculino , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Rosiglitazona , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
19.
Drug Dev Ind Pharm ; 42(2): 280-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26165244

RESUMO

OBJECTIVE: The main objective of this study was to develop and evaluate a W/O microemulsion formulation of troxerutin to improve its oral bioavailability. METHODS: The W/O microemulsion was optimized using a pseudo-ternary phase diagram and evaluated for physical properties. In vitro MDCK cell permeability studies were carried out to evaluate the permeability enhancement effect of microemulsion, and in vivo absorption of troxerutin microemulsion in the intestine was compared with that of solution after single-dose administration (56.7 mg/kg) in male Wistar rats. RESULTS: The optimal formulation consisted of lecithin, ethanol, isopropyl myristate and water (23.30/11.67/52.45/12.59 w/w) was physicochemical stable and the mean droplet size was about 50.20 nm. In vitro study, the troxerutin-loaded microemulsion showed higher intestinal membrane permeability across MDCK monolayer when compared with the control solution. The W/O microemulsion can significantly promote the intestinal absorption of troxerutin in rats in vivo, and the relative bioavailability of the microemulsion was about 205.55% compared to control solution. CONCLUSION: These results suggest that novel W/O microemulsion could be used as an effective formulation for improving the oral bioavailability of troxerutin.


Assuntos
Anticoagulantes/administração & dosagem , Sistemas de Liberação de Medicamentos , Hidroxietilrutosídeo/análogos & derivados , Administração Oral , Animais , Anticoagulantes/farmacocinética , Disponibilidade Biológica , Permeabilidade da Membrana Celular , Química Farmacêutica/métodos , Cães , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Emulsões , Hidroxietilrutosídeo/administração & dosagem , Hidroxietilrutosídeo/farmacocinética , Absorção Intestinal , Células Madin Darby de Rim Canino , Masculino , Tamanho da Partícula , Permeabilidade , Ratos , Ratos Wistar , Água/química
20.
Chemosphere ; 137: 14-24, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25966445

RESUMO

Human milk samples were collected from 150 mothers in 2011 and 2012 in Shanghai, China and analyzed for 17 polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and 12 dioxin-like polychlorinated biphenyls (DL-PCBs). The up-bound Toxic Equivalent Quantity (TEQ) ranged from 0.27 to 16.8 pg TEQ/g lipid (mean 5.4 pg TEQ/g lipid) for ∑PCDD/Fs and from 0.75 to 10.2 pg TEQ/g lipid (mean 2.9 pg TEQ/g lipid) for ∑DL-PCBs. TEQs in our study were lower than those in most countries worldwide, and displayed a notable uptrend, in contrast with those in China's national survey in 2007. TEQs in mother milks from urban areas were higher than those from rural areas, and an orderly distribution was found in four geographical regions: Eastern China>Central China≈Southwestern China>Northwestern China. Levels of analytes in Shanghai native mothers' milk ranked the first among those from all provinces and cities investigated. Migrant mothers to Shanghai from other inland provinces could potentially represent the population for exposure and risk assessment in their birth and grown-up places. Both the distribution and the uptrend were associated with release of these pollutants due to rapid industrialization and urbanization in China. Fine correlations were observed between TEQs and age of mothers, and weak correlations between TEQs and consumption of meat & meat products. Participants, who preferred both fresh water and marine fish to freshwater fish only, were prone to be exposed to higher level of PCBs. The estimated daily intake (EDI) doses for breastfed neonates entirely exceeded the tolerable intake dose by WHO.


Assuntos
Benzofuranos/análise , Monitoramento Ambiental/estatística & dados numéricos , Poluentes Ambientais/análise , Leite Humano/química , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análogos & derivados , Polímeros/análise , Adolescente , Adulto , Animais , Aleitamento Materno , China , Feminino , Peixes , Humanos , Recém-Nascido , Masculino , Mães , Dibenzodioxinas Policloradas/análise , Medição de Risco , Fatores de Tempo , Adulto Jovem
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