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1.
J Thorac Dis ; 15(9): 5122-5133, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37868901

RESUMEN

Background: Acquired intrathoracic nonmalignant tracheoesophageal fistulas (TEFs) are rare and challenging surgical problems. They can constitute a life-threatening condition due to severe pulmonary complications and poor nutrition. Surgical treatment is effective for most patients undergoing operative repair. However, in recent studies, the difficult-to-ignore early complications of surgical treatment can be as high as 62.5%. Among them, esophageal stricture occurring in 42-54% of patients, anastomosis leakage occurs at a rate of 22.7-26%, and the mortality rate can be as high as 29.4%. Here, we introduce our innovative experience repairing acquired TEFs with a thoracoacromial artery perforator flap, in which provides a clear surgical field of view, reliable reconstruction, and no serious complications during the perioperative period and no mortality or complications were observed within 180 days after the operation. Case Description: Surgical repair with a thoracoacromial artery perforator flap through a midsternal incision approach was performed in 3 patients. During the procedure, a midsternal incision was made. After the thymus and anterior mediastinal fat were resected, and the left innominate vein was transected, the trachea and esophagus were mobilized. The trachea was incised and pulled to the cranial and caudal sides. Then, the thoracoacromial artery perforator flap was harvested and transferred into the superior mediastinum for esophageal reconstruction. Subsequently, the trachea was anastomosed end to end after debridement, and the left innominate vein was either anastomosed or not. Two patients developed esophageal anastomotic leakage postoperatively and healed well after nonsurgical treatment. No mortality or other complications were observed at 180 days after the operation. Conclusions: Repair of acquired TEFs using a thoracoacromial artery perforator flap through a midsternal incision approach is an effective, safe surgical treatment.

2.
Regul Toxicol Pharmacol ; 145: 105500, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37866700

RESUMEN

The toxic equivalency factors (TEFs) approach for dioxin-like chemicals (DLCs) is currently based on a qualitative assessment of a heterogeneous data set of relative estimates of potency (REPs) spanning several orders of magnitude with highly variable study quality and relevance. An effort was undertaken to develop a weighting framework to systematically evaluate and quantitatively integrate the quality and relevance for development of more robust TEFs. Six main-study characteristics were identified as most important in characterizing the quality and relevance of an individual REP for human health risk assessment: study type, study model, pharmacokinetics, REP derivation method, REP derivation quality, and endpoint. Subsequently, a computational approach for quantitatively integrating the weighting framework parameters was developed and applied to the REP2004 database. This was accomplished using a machine learning approach which infers a weighted TEF distribution for each congener. The resulting database, weighted for quality and relevance, provides REP distributions from >600 data sets (including in vivo and in vitro studies, a range of endpoints, etc.). This weighted database provides a flexible platform for systematically and objectively characterizing TEFs for use in risk assessment, as well as providing information to characterize uncertainty and variability. Collectively, this information provides risk managers with information for decision making.


Asunto(s)
Dioxinas , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Humanos , Dioxinas/toxicidad , Medición de Riesgo , Incertidumbre , Bases de Datos Factuales
3.
Environ Sci Pollut Res Int ; 29(50): 76378-76393, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35668257

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) are widespread toxic pollutants in the atmosphere and have attracted much attention for decades. In this study, we compared the health risks of PAHs based on different toxic equivalent factors (TEFs) in a heavily polluted area during heating and non-heating periods. We also pay attention to occupancy probability (OP) in different polluted areas. The results showed that there were big differences for calculations by different TEFs, and also by OP or not. Age groups except adults were all lower calculated by OP than not. The sensitivity analysis results on the incremental lifetime cancer risks (ILCR) for population groups by Monte Carlo simulation identified that the cancer slope factor extremely affected the health risk assessment in heating periods, followed by daily inhalation exposure levels. However, daily inhalation exposure levels have dominated the effect on the inhalation ILCR and then followed by the cancer slope factor in non-heating periods. The big differences by different calculations investigated that it is important to set up the correlations between the pollution level and health risks, especially for the longtime health assessment.


Asunto(s)
Contaminantes Atmosféricos , Neoplasias , Hidrocarburos Policíclicos Aromáticos , Adulto , Contaminantes Atmosféricos/análisis , China/epidemiología , Monitoreo del Ambiente , Humanos , Exposición por Inhalación/análisis , Neoplasias/inducido químicamente , Neoplasias/epidemiología , Material Particulado/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Probabilidad , Medición de Riesgo
4.
Regul Toxicol Pharmacol ; 101: 12-23, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30359698

RESUMEN

The application of toxic equivalency factors (TEFs) or toxic units to estimate toxic potencies for mixtures of chemicals which contribute to a biological effect through a common mechanism is one approach for filling data gaps. Toxic Equivalents (TEQ) have been used to express the toxicity of dioxin-like compounds (i.e., dioxins, furans, and dioxin-like polychlorinated biphenyls (PCBs)) in terms of the most toxic form of dioxin: 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). This study sought to integrate two data gap filling techniques, quantitative structure-activity relationships (QSARs) and TEFs, to predict neurotoxicity TEQs for PCBs. Simon et al. (2007) previously derived neurotoxic equivalent (NEQ) values for a dataset of 87 PCB congeners, of which 83 congeners had experimental data. These data were taken from a set of four different studies measuring different effects related to neurotoxicity, each of which tested overlapping subsets of the 83 PCB congeners. The goals of the current study were to: (i) evaluate an alternative neurotoxic equivalent factor (NEF) derivations from an expanded dataset, relative to those derived by Simon et al. and (ii) develop QSAR models to provide NEF estimates for the large number of untested PCB congeners. The models used multiple linear regression, support vector regression, k-nearest neighbor and random forest algorithms within a 5-fold cross validation scheme and position-specific chlorine substitution patterns on the biphenyl scaffold as descriptors. Alternative NEF values were derived but the resulting QSAR models had relatively low predictivity (RMSE ∼0.24). This was mostly driven by the large uncertainties in the underlying data and NEF values. The derived NEFs and the QSAR predicted NEFs to fill data gaps should be applied with caution.


Asunto(s)
Contaminantes Ambientales/toxicidad , Síndromes de Neurotoxicidad , Bifenilos Policlorados/toxicidad , Animales , Encéfalo/metabolismo , Calcio/metabolismo , Dopamina/metabolismo , Contaminantes Ambientales/química , Células PC12 , Bifenilos Policlorados/química , Proteína Quinasa C/metabolismo , Relación Estructura-Actividad Cuantitativa , Ratas , Medición de Riesgo , Canal Liberador de Calcio Receptor de Rianodina/metabolismo
5.
Toxicol Rep ; 4: 1-8, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28959619

RESUMEN

A risk assessment of basil-based pesto sauces containing methyleugenol and related alkenylbenzenes was performed based on their levels detected in a series of pesto sauces available on the Dutch market. The estimated daily intake (EDI) values of alkenylbenzenes as a result of consumption of the different pesto sauces amounted to 1.2-44.3 µg/kg bw for individual alkenylbenzenes, 14.3-43.5 µg/kg bw when adding up the alkenylbenzene levels assuming equal potency, and 17.3-62.9 µg/kg bw when expressed in methyleugenol equivalents using alkenylbenzenes defined toxic equivalency factors (TEF). The margin of exposure approach (MOE), used to evaluate the potential risks, resulted in MOE values that were generally lower than 10000 indicating a priority for risk management when assuming daily consumption. The levels of methyleugenol detected in the pesto sauces would allow consumption of 1.1-29.8, 7.5-208, 15.1-416.5, and 32.4-892.5 g of pesto sauce on a daily basis, once a week, once every two weeks, and once a month, respectively, to achieve MOE values above the 10000 limit indicating low priority for risk management. It is concluded that consumption of pesto sauces would only be of concern if consumed on a daily basis over longer periods of time.

6.
J Appl Toxicol ; 37(10): 1254-1264, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28556924

RESUMEN

A risk assessment of nutmeg-based plant food supplements (PFS) containing different alkenylbenzenes was performed based on the alkenylbenzene levels quantified in a series of PFS collected via the online market. The estimated daily intake (EDI) of the alkenylbenzenes amounted to 0.3 to 312 µg kg-1 body weight (bw) for individual alkenylbenzenes, to 1.5 to 631 µg kg-1 bw when adding up the alkenylbenzene levels assuming equal potency, and to 0.4 to 295 µg kg-1 bw when expressed in safrole equivalents using toxic equivalency factors (TEFs). The margin of exposure approach (MOE) was used to evaluate the potential risks. Independent of the method used for the intake estimate, the MOE values obtained were generally lower than 10000 indicating a priority for risk management. When taking into account that PFS may be used for shorter periods of time and using Haber's rule to correct for shorter than lifetime exposure it was shown that limiting exposure to only 1 or 2 weeks would result in MOE values that would be, with the presently determined levels of alkenylbenzenes and proposed uses of the PFS, of low priority for risk management (MOE > 10000). It is concluded that the results of the present paper reveal that nutmeg-based PFS consumption following recommendations for daily intake especially for longer periods of time raise a concern. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Benceno/toxicidad , Carcinógenos/toxicidad , Daño del ADN/efectos de los fármacos , Contaminación de Alimentos/análisis , Myristica/química , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Humanos , Medición de Riesgo
7.
Environ Toxicol Chem ; 35(1): 173-81, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26202062

RESUMEN

Dioxin-like compounds of varying toxicities are found in complex mixtures. The toxic equivalency factor (TEF) approach was developed based on the potency of a dioxin-like compound relative to the potency of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) to streamline risk assessment. One limitation of the TEF approach is uncertainty regarding differences in the relative potency of dioxin-like compounds among different species. Relative potencies among fishes are limited, relative to relative potencies among birds and mammals, and TEFs for fishes are based entirely on the model species, rainbow trout (Oncorhynchus mykiss). An in vitro liver explant assay was used to characterize species-specific responses with regard to up-regulation of CYP1A transcript after exposure to 6 dioxin-like compounds in rainbow trout, white sturgeon (Acipenser transmontanus), lake sturgeon (Acipenser fulvescens), and northern pike (Esox lucius). Differences in sensitivities were observed among species after exposure to dioxin-like compounds. The relative potencies developed from liver explants of rainbow trout were comparable to relative potencies developed from embryo toxicity assays. Differences in relative potencies between species with the least and greatest relative potencies were up to 40-fold. To compare relative potencies among species, concentrations of dioxin-like compounds in fish eggs in the Fraser River and in Lake Ontario were used to calculate toxic equivalency quotients (TEQs) determined from TEFs or TCDD equivalents determined from relative potencies. The TEQs underestimated TCDD equivalents for white sturgeon, lake sturgeon, and northern pike, indicating uncertainty in application of TEFs to diverse fishes.


Asunto(s)
Benzofuranos/toxicidad , Dioxinas/toxicidad , Peces , Bifenilos Policlorados/toxicidad , Contaminantes Químicos del Agua/toxicidad , Alternativas a las Pruebas en Animales , Animales , Citocromo P-450 CYP1A1/biosíntesis , Citocromo P-450 CYP1A1/genética , Esocidae , Técnicas In Vitro , Oncorhynchus mykiss , Medición de Riesgo , Ríos , Especificidad de la Especie
8.
Ecotoxicol Environ Saf ; 108: 120-8, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25050801

RESUMEN

A comprehensive investigation of the levels, distribution patterns, and sources of polycyclic aromatic hydrocarbons (PAHs) in agricultural soils of the coal production area surrounding Xinzhou, China, was conducted, and the potential human health risks associated with the levels observed were addressed. A total of 247 samples collected from agricultural soils from the area were analyzed for sixteen PAHs, including highly carcinogenic isomers. The PAH concentrations had a range of n.d. to 782ngg(-1), with a mean value of 202ngg(-1). The two-three ring PAHs were the dominant species, making up 60 percent of total PAHs. Compared with the pollution levels and carcinogenic potential risks reported in other studies, the soil PAH concentrations in the study area were in the low to intermediate range. A positive matrix factorization model indicates that coal/biomass combustion, coal and oil combustion, and coke ovens are the primary PAH sources, accounting for 33 percent, 26 percent, and 24 percent of total PAHs, respectively. The benzo[a]pyrene equivalent (BaPeq) concentrations had a range of n.d. to 476ngg(-1) for PAH7c, with a mean value of 34ngg(-1). The BaPeq concentrations of PAH7c accounted for more than 99 percent of the ∑PAH16, which suggests that seven PAHs were major carcinogenic contributors of ∑PAH16. According to the Canadian Soil Quality Guidelines, only six of the soil samples had concentrations above the safe BaPeq value of 600ngg(-1); the elevated concentrations observed at these sites can be attributed to coal combustion and industrial activities. Exposure to these soils through direct contact probably poses a significant risk to human health as a result of the carcinogenic effects of PAHs.


Asunto(s)
Carcinógenos/toxicidad , Neoplasias/inducido químicamente , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes del Suelo/análisis , Suelo/química , Agricultura , Carcinógenos/análisis , China , Carbón Mineral , Contaminación Ambiental/análisis , Humanos , Medición de Riesgo
9.
Atherosclerosis ; 230(1): 1-5, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23958244

RESUMEN

BACKGROUND: Background exposure to persistent organic pollutants (POPs) has emerged as a new risk factor for metabolic syndrome (MetS), while hyperuricemia is associated with MetS through unclear mechanisms. OBJECTIVE: We examined cross-sectional data for consistency with the hypothesis that POPs are a common underlying risk factor of both MetS and hyperuricemia. METHODS: We evaluated associations of POPs with hyperuricemia in subjects aged ≥20 years in the population-based National Health and Nutrition Examination Survey (NHANES) 2003-2004. Sample size was n = 1331 for organochlorine (OC) pesticides and n = 1299 for polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs). RESULTS: Among all subjects, the risk of hyperuricemia was higher for higher serum concentrations of OC pesticides, PCDDs, and dioxin-like PCBs. PCDFs and nondioxin-like PCBs did not show any clear trend. Adjusted odds ratios (ORs) for OC pesticides, PCDDs, and dioxin-like PCBs were 1.0, 2.4, 2.3, 3.0, and 2.5 (P trend = 0.05), 1.0, 1.6, 1.4, 2.1, and 2.5 (P trend = 0.01), and 1.0, 1.3, 1.4, 1.3, and 2.4 (P trend = 0.04). When we restricted the analyses to subjects without MetS, all these associations appeared to strengthen. CONCLUSION: This study is consistent with our hypothesis that the risk of hyperuricemia relates to background exposure to a mixture of POPs even among persons without MetS. There should be further research about whether avoiding exposure to POPs and otherwise decreasing body burden of POPs would be helpful to prevent or manage hyperuricemia or gout.


Asunto(s)
Contaminantes Ambientales/sangre , Hiperuricemia/sangre , Hiperuricemia/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Benzofuranos/sangre , Cloro/sangre , Estudios Transversales , Dibenzofuranos Policlorados , Dioxinas/sangre , Femenino , Humanos , Masculino , Síndrome Metabólico/sangre , Persona de Mediana Edad , Encuestas Nutricionales , Oportunidad Relativa , Compuestos Orgánicos/sangre , Plaguicidas/sangre , Bifenilos Policlorados/sangre , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/sangre , Factores de Riesgo , Estados Unidos , Adulto Joven
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