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1.
Environ Sci Technol ; 58(4): 2089-2101, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38231021

RESUMO

North American river otters (Lontra canadensis) are top predators in riverine ecosystems and are vulnerable to per- and polyfluoroalkyl substance (PFAS) exposure. Little is known about the magnitude of exposure and tissue distribution of PFAS in river otters. We measured 45 PFAS in various tissues of 42 river otters collected from several watersheds in the state of West Virginia, USA. The median concentrations of ∑All (sum concentration of 45 PFAS) varied among tissues in the following decreasing order: liver (931 ng/g wet weight) > bile > pancreas > lung > kidney > blood > brain > muscle. Perfluoroalkylsulfonates (PFSAs) were the predominant compounds accounting for 58-75% of the total concentrations, followed by perfluoroalkyl carboxylates (PFCAs; 21-35%). 8:2 fluorotelomer sulfonate (8:2 FTS), 10:2 FTS, and 6:2 chlorinated polyfluoroalkyl ether sulfonate were frequently found in the liver (50-90%) and bile (96-100%), whereas hexafluoropropylene oxide dimer acid (HFPO-DA) was rarely found. The hepatic concentrations of ∑All in river otters collected downstream of a fluoropolymer production facility located along the Ohio River were 2-fold higher than those in other watersheds. The median whole body burden of ∑All was calculated to be 1580 µg. PFOS and perfluorooctanoic acid (PFOA) concentrations in whole blood of some river otters exceeded the human toxicity reference values, which warrant further studies.


Assuntos
Fluorocarbonos , Lontras , Poluentes Químicos da Água , Animais , Humanos , West Virginia , Ecossistema , Fluorocarbonos/análise , Fígado , Poluentes Químicos da Água/análise
2.
Environ Sci Technol ; 57(15): 6129-6138, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37010350

RESUMO

1,3-Diphenylguanidine (DPG), 1,3-di-o-tolylguanidine (DTG), and 1,2,3-triphenylguanidine (TPG) are synthetic chemicals widely used in rubber and other polymers. Nevertheless, limited information is available on their occurrence in indoor dust. We measured these chemicals in 332 dust samples collected from 11 countries. DPG, DTG, and TPG were found in 100%, 62%, and 76% of the house dust samples, at median concentrations of 140, 2.3, and 0.9 ng/g, respectively. The sum concentrations of DPG and its analogues varied among the countries in the following decreasing order: Japan (median: 1300 ng/g) > Greece (940) > South Korea (560) > Saudi Arabia (440) > the United States (250) > Kuwait (160) > Romania (140) > Vietnam (120) > Colombia (100) > Pakistan (33) > India (26). DPG accounted for ≥87% of the sum concentrations of the three compounds in all countries. DPG, DTG, and TPG exhibited significant correlations (r: 0.35-0.73; p < 0.001). Elevated concentrations of DPG were found in dust from certain microenvironments (e.g., offices and cars). Human exposure to DPG through dust ingestion were in the ranges 0.07-4.40, 0.09-5.20, 0.03-1.70, 0.02-1.04, and 0.01-0.87 ng/kg body weight (BW)/day for infants, toddlers, children, teenagers, and adults, respectively.


Assuntos
Poluição do Ar em Ambientes Fechados , Exposição Ambiental , Adulto , Lactente , Adolescente , Humanos , Estados Unidos , Exposição Ambiental/análise , Poeira/análise
3.
Environ Sci Technol ; 57(24): 8883-8889, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37288988

RESUMO

1,3-Diphenylguanidine (DPG), 1,3-di-o-tolylguanidine (DTG), and 1,2,3-triphenylguanidine (TPG) are rubber additives widely present in the indoor environment. Nevertheless, little is known about their human exposure. We developed a method for the quantification of DPG, DTG, and TPG in human urine, using high-performance liquid chromatography-tandem mass spectrometry. The quantitative analysis of target analytes at parts-per-trillion levels in urine was optimized using hydrophilic-lipophilic balanced solid-phase extraction and isotopic dilution. The method limits of detection and quantification were in the range of 0.002-0.02 and 0.005-0.05 ng/mL, respectively. The recoveries of all analytes in human urine fortified at 1, 5, 10, and 20 ng/mL concentrations were in the range of 75.3-111%, with standard deviations of 0.7-4%. The repeated measurement of similarly fortified human urine yielded intra-day and inter-day variations of 0.47-3.90 and 0.66-3.76%, respectively. The validated method was applied in the measurement of DPG, DTG, and TPG in real human urine samples, which revealed the occurrence of DPG in children's urine samples (n = 15) with a detection frequency of 73% and at a median concentration of 0.05 ng/mL. DPG was found in 20% of adults' urine samples (n = 20).


Assuntos
Guanidinas , Espectrometria de Massas em Tandem , Criança , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Extração em Fase Sólida
4.
Environ Sci Technol ; 56(17): 12473-12482, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35951380

RESUMO

Benzophenone (BP)-type ultraviolet (UV) filters are estrogenic chemicals used extensively in sunscreen products, leading to concerns over human exposure. To assess exposure to BP derivatives in sunscreens, we tested 14 BP UV filters in 50 products representing 44 brands marketed in the United States in 2021, finding BP, 2-hydroxy-4-methoxybenzophenone (BP-3 or oxybenzone), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), 2-hydroxy-4-methoxy-4'-methylbenzophenone (BP-10), 2,3,4-trihydroxybenzophenone (2,3,4-OH-BP), and 4-methylbenzophenone (4-Me-BP) in ≥70% of the samples. The geometric mean (GM) concentration of the sum of these BPs (∑14BPs) in the 50 products was 6600 ng/g. BP-3 was the predominant BP in oxybenzone-containing products (accounting for >99% of the total concentration), with a concentration 5-6 orders of magnitude higher than that in "oxybenzone-free" products (GM: 35 600 000 vs 113 ng/g). BP was present in >90% of products analyzed, including those labeled "oxybenzone-free" (GM: 2100 ng/g). BP concentrations were ∼100-fold higher in octocrylene-containing vs "octocrylene-free" products (GM: 15900 vs 151 ng/g). Dermal exposure doses of BP-3 from oxybenzone-containing products (GM: 4140 000 ng/kg body weight (BW)/day) and of BP in some (24%) octocrylene-containing products (GM: 12 200 ng/kg BW/day) were above reference values (2 000 000 and 30 000 ng/kg BW/day for BP-3 and BP, respectively). This study provides evidence that BP and BP-3 concentrations in sunscreen products vary widely and may be noteworthy even in products labeled oxybenzone- or octocrylene-free, making dermal exposure a continuing concern.


Assuntos
Benzofenonas , Protetores Solares , Humanos , Estados Unidos
5.
J Environ Manage ; 324: 116301, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36179468

RESUMO

Red mud (RM), a kind of iron-rich industrial waste produced in the alumina production process, can be utilized as a potential iron-based material for the removal of refractory organic pollutants from wastewater in advanced oxidation processes (AOPs). In this work, high-iron RM (rich in iron) was activated in a ball mill and applied as an effective activator of peroxymonosulfate (PMS) for tetracycline hydrochloride (TC-HCl) degradation. Compared with that of unmilled RM (69.7%), the TC-HCl decomposition ratios of ball-milled RM (BM-RM) (72.2%-92.0%) were all improved in the presence of PMS. Systematic characterization suggested that ball milling could optimize the physicochemical properties of RM, such as increased surface area, increased oxygen vacancies, enhanced electrical conductivity, and increased exposure of Fe(II) sites, all of which could effectively improve RM for PMS activation to degrade TC-HCl. The quenching experiments and electron paramagnetic resonance technique revealed that 1O2 and SO4·- contributed dominantly to the TC-HCl degradation. Ultra performance liquid chromatography mass spectrometry analysis combined with density functional theory calculation revealed that the degradation pathways of TC-HCl were driven by hydroxylation, N-demethylation and dehydration in BM-RM/PMS system. Based on quantitative structure-activity relationship prediction using the Toxicity Estimation Software Tool software, the toxicity of almost all intermediates was significantly reduced. An obvious inhibition effect on TC-HCl was occurred in the presence of Cl-, whereas the presences of NO3- and SO42- had little effect. However, HCO3- improved TC-HCl removal efficiency. BM-RM had a wide working pH range (pH = 3-11) and showed good stability and reusability in use. Overall, this work not only offers a simple and promising approach to improve the catalytic activity of RM, but also opens new insights into the ball-milled RM as an effective PMS activator for wastewater treatment.


Assuntos
Peróxidos , Tetraciclina , Peróxidos/química , Catálise , Ferro/química
6.
J Autoimmun ; 122: 102666, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34144327

RESUMO

BACKGROUND: BALB/c mice which received long-term immunizations of adenovirus (Ad) expressing thyrotropin receptor A-subunits (TSHR) developed stable Graves' disease (GD). TSHR-derived cyclic peptide 19 (P19) was identified as effective therapy in this model. METHODS: In Ad-TSHR mice, we investigated shorter disease intervals up to 4 months for histological alterations of the orbits, fine tuning of anti-TSHR antibodies (Ab) and free thyroxine (fT4) hormone levels by using novel detection methods in an independent laboratory. Therapy (0.3 mg/kg P19 or vehicle) was given intravenously after the fourth Ad-TSHR immunization (week 11) and continued until week 19. RESULTS: Thyrotropin binding inhibitory immunoglobulins (TBII, bridge immunoassay), blocking (TBAb) and stimulating (TSAb) TSHR-Ab (both cell-based bioassays) and serum levels of fT4 were significantly elevated at week 11 in Ad-TSHR-immunized mice versus none in control mice. For the first time, TSAb, TBAb, and thyroperoxidase-Ab were detected in 17 of 19, 12/19 and 6/19 Ad-TSHR immunized mice, respectively at week 21. Also, for the first time, this study showed that P19 treatment markedly reduced serum TBII (p < 0.0001), serum fT4 (p = 0.02), and acidic mucins and collagen content in the orbital tissue of Ad-TSHR-immunized mice. CONCLUSION: P19 significantly improved thyroid function, confirming previous results in an independent second laboratory. A relevant shift of anti-TSHR antibody subpopulations in response to P19 therapy may help explain its immunological effects. Moreover, P19 exerted a beneficial effect on mucine and collagen content of orbital tissue. Hence, P19 offers a potential novel therapeutic approach for GD and associated orbitopathy.


Assuntos
Doença de Graves/tratamento farmacológico , Oftalmopatia de Graves/tratamento farmacológico , Peptídeos Cíclicos/farmacologia , Animais , Colágeno/análise , Modelos Animais de Doenças , Feminino , Doença de Graves/sangue , Doença de Graves/imunologia , Doença de Graves/fisiopatologia , Oftalmopatia de Graves/imunologia , Oftalmopatia de Graves/patologia , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Imunoglobulinas Estimuladoras da Glândula Tireoide/imunologia , Camundongos , Mucinas/análise , Órbita/efeitos dos fármacos , Órbita/patologia , Peptídeos Cíclicos/genética , Peptídeos Cíclicos/uso terapêutico , Receptores da Tireotropina/administração & dosagem , Receptores da Tireotropina/genética , Receptores da Tireotropina/imunologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/imunologia , Glândula Tireoide/fisiopatologia
7.
Zhonghua Nan Ke Xue ; 27(11): 1006-1010, 2021 Nov.
Artigo em Zh | MEDLINE | ID: mdl-37422873

RESUMO

Objective: To investigate the effect of the application of scrotal midline raphe flaps in surgical repair of hypospadias with penile skin defects. METHODS: We retrospectively analyzed the clinical data on 20 cases of hypospadias with penile skin defects from January 2017 to July 2019. The patients ranged in age from 3 to 12 (mean 6.5) years, with a history of 0-4 (mean 2.4) times of penile surgery. The urethral orifice was located in the midshaft of the penis or perineum, without urethral fistula or narrowing of the outer urethral orifice. We performed ubularized incised plate (TIP) repair of the penile skin defects with scrotal midline raphe flaps and followed up the patients for 7-30 (mean 18.4) months postoperatively. RESULTS: The flaps survived well without necrosis in all the cases, and 18 (90%) of the cases were cured in the first stage. Two of the patients developed urethral fistula after removal of the catheter, which was successfully repaired at 6 months after the first operation. All the patients achieved smooth urination with no urethral stricture. The urinary flow rate was 5-9 (mean 6.5) ml/s at 6 months postoperatively. All were satisfied with the appearance of the penis and scrotum. CONCLUSIONS: The scrotal midline raphe flap, with rich blood supply and good ductility, is suitable for repair of penile skin defects. And TIP repair with the scrotal midline raphe flap, with the advantages of simple operation, few complications and good appearance of the penis and scrotum, is worthy of clinical application.

8.
Environ Sci Technol ; 54(2): 1111-1119, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31867966

RESUMO

Epidemiological studies have indicated the thyroid-disrupting effects of persistent organic pollutants (POPs). However, the association of low-exposure POPs with thyroid hormones (THs) remains unclear. Here, we aim to assess the association of low exposure of POPs, including polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polybrominated dibenzo-p-dioxins and furans, with THs [total L-thyroxine (TT4), total 3,3',5-triiodo-L-thyronine (TT3), and total 3,3',5'-triiodo-L-thyronine (TrT3)] measured in human breast milk. Ninety-nine breast milk samples were collected from the LUPE cohort (2015-2016, Bavaria, Germany). Fourteen PBDEs, 17 PCBs, and 5 PCDD/Fs had quantification rates of >80%. Nonmonotonic associations were observed. In adjusted single-pollutant models, (1) TT4 was inversely associated with BDE-99, -154, and -196; (2) TT3 was inversely associated with BDE-47, -99, -100, -197, -203, -207, and OCDD; and (3) TrT3 was inversely associated with BDE-47, -99, -183, and -203. Multipollutant analysis using principal component analysis and hierarchical clustering revealed inverse associations of PBDEs (BDE-28, -47, -99, -100, -154, -183, and -197) with TT4 and TrT3. These results indicate that POPs at low levels might be related to reduced THs. This study shows that human breast milk might be an appropriate specimen to evaluate the thyroid disruption of POPs.


Assuntos
Poluentes Ambientais , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Animais , Dibenzofuranos , Feminino , Alemanha , Éteres Difenil Halogenados , Homeostase , Humanos , Leite Humano , Hormônios Tireóideos
9.
Public Health Nutr ; 22(6): 1048-1055, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30587262

RESUMO

OBJECTIVE: To explore the direct and indirect associations of dietary patterns with hypertension using structural equation modelling (SEM). DESIGN: Factor analysis with varimax rotation was used to classify different dietary patterns and SEM was employed to investigate the associations of dietary patterns with hypertension. Total cholesterol to HDL-cholesterol (TC:HDL-C) ratio and LDL-cholesterol to HDL-cholesterol (LDL-C:HDL-C) ratio were used as observed indicator variables of the lipid latent variable. Waist circumference, body fat percentage and BMI, which were associated with hypertension, were used as observed indicator variables of the obesity latent variable. SETTING: International Chronic Disease Cohort (ICDC) that began in 2005 with the purpose of describing the frequency and determinants of chronic diseases in Jilin Province, China. PARTICIPANTS: A total of 1492 adults (40-79 years) were enrolled in the baseline study from August 2010 to August 2011. RESULTS: Hypertension prevalence in our study population was 34·9 %. It was found that the wine pattern, condiment pattern, obesity latent variable, lipid latent variable, glucose, age and family history of hypertension were factors that had an association with hypertension via SEM, and the corresponding coefficients were 0·056, 0·011, 0·230, 0·281, 0·098, 0·232 and 0·116, respectively. CONCLUSIONS: The wine pattern and lipid latent variable had positive direct associations with hypertension. The condiment pattern had a positive indirect association with hypertension via the obesity latent variable. The vegetables pattern, modern pattern and snack pattern were not associated with hypertension.

10.
Water Sci Technol ; 2017(2): 473-480, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29851400

RESUMO

In this study, using bentonite-supported Fe(II)/phosphotungstic acid composite (HPW-Fe-Organicbent) prepared by mechanochemical synthesis as heterogeneous catalyst, the photo-Fenton degradation of ethyl xanthate under visible light irradiation was studied in detail. The results showed that the degradation of ethyl xanthate was mainly impacted by H2O2 dosage, catalyst dosage and reaction time. HPW-Fe-Organicbent catalyst had a wide applicable range of pH and kept a high catalytic activity even at high pH in the photo-Fenton degradation of ethyl xanthate. It was found that the degradation of ethyl xanthate in the photo-Fenton process catalyzed by HPW-Fe-Organicbent mainly resulted from the hydroxyl radicals. HPW-Fe-Organicbent had an excellent stability in use, and retained almost all of its catalytic activity for four recycling times. Moreover, the kinetics study showed the degradation of ethyl xanthate, with the initial concentration below 50 mg/L, was well fitted by the pseudo-first-order rate model.


Assuntos
Bentonita/análise , Compostos Ferrosos/análise , Peróxido de Hidrogênio/química , Ácido Fosfotúngstico/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Cinética , Luz , Fotólise
11.
Circulation ; 133(21): 2018-29, 2016 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-27048765

RESUMO

BACKGROUND: Evidence that vena cava filters (VCFs) are beneficial is limited. METHODS AND RESULTS: We retrospectively analyzed all noncancer patients admitted to nonfederal California hospitals for acute venous thromboembolism from 2005 to 2010. Analysis was stratified by the presence/absence of a contraindication to anticoagulation (active bleeding, major surgery). Outcomes were death within 30 or 90 days of admission and the 1-year incidence of recurrent venous thromboembolism manifested as pulmonary embolism or deep vein thrombosis. Propensity score methods were used to account for observed systematic differences in baseline characteristics between patients treated and those not treated with a VCF. Among 80 697 patients with no contraindication to anticoagulation, VCF use (n=7762, 9.6%) did not significantly reduce the 30-day risk of death (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.98-1.28). Among 3017 patients with active bleeding, VCF use (n=1095, 36.3%) reduced the 30-day risk of death by 32% (HR, 0.68; 95% CI, 0.52-0.88) and the 90-day risk by 27% (HR, 0.73; 95% CI, 0.59-0.90). VCF use (n=489, 33.8%) did not reduce mortality among 1445 patients who underwent major surgery (HR, 1.1; 95% CI, 0.71-1.77). In all subgroups, filter use did not reduce the risk of subsequent pulmonary embolism. However, the risk of subsequent deep vein thrombosis increased by 50% among VCF patients with no contraindication (HR, 1.53; 95% CI, 1.34-1.74) and by 135% among VCF patients with active bleeding (HR, 2.35; 95% CI, 1.56-3.52). CONCLUSIONS: VCF use significantly reduced the short-term risk of death only among patients with acute venous thromboembolism who had a contraindication to anticoagulation because of active bleeding. These results support the findings of a randomized clinical trial and current guidelines that recommend VCF use only in patients who cannot receive anticoagulation treatment.


Assuntos
Neoplasias , Vigilância da População , Filtros de Veia Cava/estatística & dados numéricos , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/terapia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Retrospectivos , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico
12.
J Cardiothorac Vasc Anesth ; 31(3): 853-862, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28302346

RESUMO

OBJECTIVES: This study assessed the effect of 2 types of hydroxyethyl starches (HES) on renal integrity and blood transfusion in cardiac surgery patients. DESIGN: Retrospective investigation. SETTING: Patients from a single tertiary medical center. PARTICIPANTS: Inclusion criteria included coronary artery bypass graft (CABG) and/or valve surgery that included cardiopulmonary bypass with aortic cross-clamping. INTERVENTIONS: Intraoperative HES and blood product administration. MEASUREMENTS AND MAIN RESULTS: The study comprised 1,265 patients who met inclusion criteria. Of these patients, 70% received HES, and of these, 47% received<1,000 mL and 53% received≥1,000 mL. There was no difference in the development of acute kidney injury between the 2 groups. A parsimonious propensity model for colloids showed that combined CABG and valve surgery were less likely to be associated with HES administration than was CABG alone (OR 0.68, confidence interval [CI] 0.46-0.97; p = 0.04). Intra-aortic balloon pump use was less likely to be associated with HES administration (OR 0.57, CI 0.38-0.86; p = 0.007). Patients with chronic kidney disease, stages 3 to 5, were less likely to receive HES, with an OR of 0.56 (CI 0.38-0.84; p = 0.004); 0.51 (CI 0.20-1.33; p = 0.170); and 0.23 (CI 0.12-0.44; p<0.0001), respectively, for each stage. No difference was noted in red blood cell transfusion. However, fresh frozen plasma, cryoprecipitate, and platelet transfusions were significantly higher with larger volumes of HES, with an OR of 2.03 (CI 1.64-2.52; p<0.001); 1.60 (CI 1.30-1.97; p<0.000); and 1.62 (CI 1.21-2.15; p = 0.006), respectively. No differences in surgical mortality were found between the colloid and noncolloid groups. CONCLUSIONS: This study showed no association of postoperative acute kidney injury and red blood cell transfusion between the colloid and noncolloid groups. Although the complication rate was higher with HES administration, there was no difference in surgery mortality between the 2 groups.


Assuntos
Injúria Renal Aguda/terapia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transfusão de Eritrócitos/tendências , Derivados de Hidroxietil Amido/administração & dosagem , Cuidados Intraoperatórios/tendências , Complicações Pós-Operatórias/terapia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Idoso , Coloides/administração & dosagem , Transfusão de Eritrócitos/métodos , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Masculino , Pessoa de Meia-Idade , Substitutos do Plasma/administração & dosagem , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
13.
J Membr Biol ; 249(1-2): 119-28, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26501871

RESUMO

Endothelin-1 (ET-1), a member of endothelins family, binds to ETA receptor (ETAR) and ETB receptor to exert its role in multiple cellular processes. Although ET-1 and its receptors has been reported to be overexpressed in many cancers, and overexpression of ET-1 is able to trigger hepatocarcinogenesis in zebrafish, the functions of ET-1 and its receptors in hepatocellular carcinoma (HCC) cell migration and invasion remain unclear. In the present study, we found that ETAR was greatly expressed in HCC cells and HCC tissues. ETAR expression as well as ET-1 expression was associated with vascular invasion and tumor stage in HCC. Activation of ETAR by ET-1 dose-dependently promoted cell migration and invasion of HCC cells, while silencing of ETAR by siRNA or blocking of ETAR by specific inhibitor resulted in significant reduction in ET-1-mediated migration and invasion. Furthermore, ET-1 induced activation of ERK1/2 and AKT and increased MMP-3 production via ETAR. In addition, using inhibitors of ERK1/2 and AKT, we found that ERK1/2 and AKT pathways were both involved in ETAR-mediated migration, invasion, and MMP-3 production. Taken together, our findings suggest that activation of ETAR by ET-1 promotes HCC cell migration and invasion via activating ERK1/2 and AKT signaling pathways and upregulating MMP-3 expression. Thus, ETAR may play an important role in the progress of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Endotelina-1/metabolismo , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Endotelina/metabolismo , Transdução de Sinais , Adulto , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Endotelina-1/genética , Feminino , Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Metaloproteinase 3 da Matriz/biossíntese , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Isoformas de Proteínas , Receptores de Endotelina/genética , Carga Tumoral
14.
Med Sci Monit ; 22: 855-62, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26978735

RESUMO

BACKGROUND: Previous studies showed the aberrant expression of microRNA-182 (miR-182) in glioma tissue. However, the exact role of circulating miR-182 in glioma remains unclear. Here, we confirmed the expression of plasma circulating miR-182 in glioma patients, and further explored its potential diagnostic and prognostic value. MATERIAL/METHODS: Real-time quantitative PCR (RT-PCR) was used to measure circulating cell-free miR-182 from 112 glioma patients and 54 healthy controls. RESULTS: Our findings showed that the level of circulating miR-182 in glioma patients was higher than that in healthy controls (P<0.001), which was significantly associated with KPS score (P=0.025) and WHO grade (P<0.001). The area under the receiver operating characteristic (ROC) curve (AUC) was 0.778. The optimal cut-off value was 1.56, and the sensitivity and specificity were 58.5% and 85.2%, respectively. Interestingly, a high predictive value of circulating miR-182 was observed in high-grade glioma (AUC=0.815). However, the AUC was lower in low-grade glioma (AUC=0.621). Kaplan-Meier analysis demonstrated that the cumulative 5-year overall survival rate in the high miR-182 group was significantly lower than that in the low miR-182 group in both overall survival (OS) (P=0.003) and disease-free survival (DFS) (P=0.006). Moreover, multivariate Cox analysis revealed that circulating miR-182 was an independent prognostic indicator for OS (P=0.034) and DFS (P=0.013). CONCLUSIONS: These results suggest that circulating miR-182 may be a potential noninvasive biomarker for the diagnosis and prognosis of human glioma.


Assuntos
Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/genética , Glioma/sangue , Glioma/genética , MicroRNAs/sangue , MicroRNAs/genética , Neoplasias Encefálicas/diagnóstico , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC
15.
Med Sci Monit ; 22: 3486-3492, 2016 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-27684457

RESUMO

BACKGROUND MGMT methylation status can influence the therapeutic effect and prognosis of glioblastoma (GBM). There are conflicting results from studies evaluating the efficacy of bevacizumab (BV) when it is combined with temozolomide (TMZ) and radiotherapy (RT) in patients diagnosed with GBM with different MGMT methylation status. MATERIAL AND METHODS Data were extracted from publications in PubMed, Embase, and The Cochrane Library, with the last search performed March 23, 2016. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained. RESULTS Data from 3 clinical trials for a total of 1443 subjects were used for this meta-analysis. MGMT methylated and unmethylated patients showed improved PFS in the BV group (pooled HRs, 0.769, 95% CIs 0.604-0.978, P=0.032; 0.675, 95%CIs 0.466-0.979, P=0.038). For patients with either type of GBM, BV did not improve the OS based on the pooled HRs 1.132 (95% CIs 0.876-1.462; P=0.345) for methylated and 1.018 (95% CIs 0.879-1.179; P=0.345) for unmethylated. CONCLUSIONS Bevacizumab combined with temozolomide-radiotherapy correlated with improved PFS for treatment of patients with different MGMT methylation status of newly diagnosed GBM. There was insufficient evidence to determine the synergistic effects of combining BV with TMZ and RT on improving survival in patients with different MGMT methylation status.

16.
J Cardiothorac Vasc Anesth ; 30(6): 1502-1508, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27435836

RESUMO

OBJECTIVE: The goal of this retrospective study was to investigate the effects of perioperative use of dexmedetomidine (Dex) on outcomes for older patients undergoing cardiac surgery. DESIGN: Retrospective investigation. SETTING: Patients from a single tertiary medical center. PARTICIPANTS: A total of 505 patients (≥65 years old) who underwent coronary artery bypass graft (CABG) or valve surgery. CABG and/or valve surgery plus other procedures were divided into 2 groups: 283 received intravenous Dex infusion (Dex group) and 222 did not (Non-Dex group). INTERVENTIONS: Perioperative Dex intravenous infusion (0.24 to 0.6 µg/kg/h) initiated after cardiopulmonary bypass and continued for<24 hours postoperatively in the ICU. MEASUREMENTS AND MAIN RESULTS: Data were risk adjusted, propensity score weighted, and multivariate logistic regression was used. The primary outcome was mortality. Secondary outcomes included postoperative stroke, coma, myocardial infarction, heart block, cardiac arrest, delirium, renal failure, and sepsis. Perioperative Dex infusion significantly decreased in-hospital mortality (0.90% v 2.83%; adjusted odds ratio (OR), 0.099; 95% confidence interval (CI), 0.030-0.324; p = 0.004) and operative mortality (1.35% v 3.18%; adjusted OR, 0.251; 95% CI, 0.077-0.813; p = 0.021). Perioperative Dex treatment also reduced the risk of stroke (0.90% v 1.77%; adjusted OR, 0.15; 95% CI, 0.038-0.590; p = 0.007), and delirium (7.21% v 10.95%; adjusted OR, 0.35; 95% CI, 0.212-0.578; p < 0.0001). CONCLUSIONS: Results from this study (ClinicalTrials.gov identifier: NCT01683448) suggested perioperative use of dexmedetomidine was associated with decreases in in-hospital and operative mortality in elderly patients following cardiac surgery. It also reduced incidences of postoperative stroke and delirium in elderly patients.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/métodos , Dexmedetomidina/uso terapêutico , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Delírio/etiologia , Delírio/prevenção & controle , Dexmedetomidina/administração & dosagem , Feminino , Valvas Cardíacas/cirurgia , Mortalidade Hospitalar , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
17.
J Cardiothorac Vasc Anesth ; 30(5): 1308-16, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27461794

RESUMO

OBJECTIVES: Body mass index (BMI) commonly is used in obesity classification as a surrogate measure, and obesity is associated with a cluster of risk factors for cardiovascular disease. The aim of this study was to investigate the impact of BMI on short-term outcomes after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: University teaching hospital, 2 centers. PARTICIPANTS: The study comprised 4,740 patients who underwent cardiac surgery at 2 hospitals-from July 1, 2001, to June 30, 2013, in 1 hospital and from September 1, 2003, to August 31, 2014, in a second hospital. INTERVENTIONS: No changes to standard practice were required. MEASUREMENTS AND MAIN RESULTS: Patients were assigned into 6 BMI groups as follows: underweight (BMI<18.5 kg/m(2)), normal weight (≥18.5 to<25 kg/m(2)), overweight (≥25 to<30 kg/m(2)), class I obese (≥30 to<35 kg/m(2)), class II obese (≥35 to<40 kg/m(2)), and class III obese (BMI≥40 kg/m(2)). Short-term major postoperative complications (postoperative stroke, cardiac arrest, new atrial fibrillation/flutter, permanent rhythm device insertion, deep sternal infection, sepsis, prolonged ventilation, pneumonia, renal dialysis, renal failure, intensive care unit readmission, total intensive care unit hours, and readmission in 30 days, and mortalities (in-hospital mortality, 30-day mortality, surgical mortality) were compared among various BMI groups after cardiac surgery. Age, sex, surgery type, family history of coronary artery disease, diabetes, hypertension, heart failure, and lipid-lowering medication were the risk factors for early outcomes. Multiple logistic regression analysis indicated that the underweight and class III obese BMI groups demonstrated significant, adverse differences in some short-term outcomes, including deep sternal infection, prolonged ventilation, new atrial fibrillation/flutter, and renal failure. However, being in the overweight or class I obese group demonstrated a positive effect on discharge and surgical mortality. CONCLUSIONS: The results of this study demonstrated that extreme obesity and underweight were significantly associated with early major adverse clinical outcomes. However, there was an "obese paradox" in short-term mortality after cardiac surgery.


Assuntos
Índice de Massa Corporal , Procedimentos Cirúrgicos Cardíacos , Obesidade/complicações , Complicações Pós-Operatórias , Magreza/complicações , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
J Arthroplasty ; 31(3): 590-5, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26525486

RESUMO

BACKGROUND: This study describes and tests a risk adjustment model developed for the California Joint Replacement Registry to report predictors of complication rates. METHODS: Complication rates were analyzed for 9960 patients enrolled in the California Joint Replacement Registry at 22 medical centers. Multivariable logistic risk models were created to analyze risks of postoperative complications. RESULTS: Age and American Society of Anesthesiologists class were the strongest predictors of complication rates (P < .0001). Congestive heart failure and peripheral vascular disease were also statistically significant predictors of complications. Three hospitals were found to have statistically significantly worse than expected complication rates, and one was found to have a better than expected complication rate after case mix risk adjustment. CONCLUSION: Adequate risk adjustment is a key element in objective comparison of surgeons, hospitals, and devices using total joint arthroplasty registry data.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Complicações Pós-Operatórias , Risco Ajustado , Idoso , Artroplastia de Quadril/estatística & dados numéricos , Artroplastia do Joelho/estatística & dados numéricos , California , Bases de Dados Factuais , Feminino , Insuficiência Cardíaca/complicações , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doenças Vasculares Periféricas/complicações , Sistema de Registros , Estudos Retrospectivos
19.
Ann Surg ; 261(1): 207-12, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24743611

RESUMO

BACKGROUND: Effects of aspirin on patients with chronic kidney disease (CKD) remains unclear. This study aimed to examine the effect of preoperative aspirin use on postoperative renal function and 30-day mortality in patients with CKD undergoing cardiac surgery. METHODS: A retrospective cohort study was performed on consecutive patients (n = 5175) receiving cardiac surgery in 2 tertiary hospitals. Of all patients, 3585 met the inclusion criteria and underwent the analysis to determine the association of preoperative aspirin with incidence of acute kidney injury (AKI) and death based on estimated glomerular filtration rate (eGFR). RESULTS: Of 3585 patients, 31.5% had CKD (eGFR < 60 mL/min/1.73 m2) at baseline and 27.6% had AKI postoperatively. The baseline eGFR had a nonlinear relationship with the incidence and stages of AKI. As eGFR decreased to 15 to 30 from more than or equal to 90 mL/min/1.73 m2, AKI and 30-day mortality increased to 50.5% from 23.5% and to 11.9% from 2.6%, respectively (P < 0.001). However, preoperative aspirin use was associated with a significant decrease in postoperative AKI and 30-day mortality in patients with CKD undergoing cardiac surgery, in particular, the survival benefit associated with aspirin was greater in patients with CKD (vs normal kidney function): 30-day mortality was reduced by 23.3%, 58.2%, or 70.0% for patients with baseline eGFR more than or equal to 90, 30 to 59, or 15 to 30 mL/min/1.73 m2, respectively (P trend < 0.001). CONCLUSIONS: For patients with CKD undergoing cardiac surgery, preoperative aspirin therapy was associated with renal protection and mortality decline. The magnitude of the survival benefit was greater in patients with CKD than normal kidney function.


Assuntos
Injúria Renal Aguda/prevenção & controle , Aspirina/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Mortalidade Hospitalar , Inibidores da Agregação Plaquetária/uso terapêutico , Cuidados Pré-Operatórios , Insuficiência Renal Crônica/complicações , Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos Cardíacos/mortalidade , Taxa de Filtração Glomerular , Humanos , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
J Nutr ; 145(6): 1249-55, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25878208

RESUMO

BACKGROUND: Few prospective studies have examined the preventive role of fruit and vegetable intakes against cancer in Asian populations. OBJECTIVE: This prospective study evaluated the associations between total fruit intake, total vegetable intake, and total fruit and vegetable intake and total cancer incidence and mortality. METHODS: This prospective cohort study included 14,198 men 40-59 y of age enrolled in the Seoul Male Cohort Study from 1991 to 1993. Fruit and vegetable intakes were assessed by a validated food-frequency questionnaire. We used Cox proportional hazard regression models to compute RR ratios and 95% CIs. RESULTS: During the follow-up period from 1993 to 2008, 1343 men were diagnosed with cancer, and 507 died of cancer. Total vegetable intake was linearly associated with cancer incidence but was nonlinearly associated with cancer mortality; by comparing ≥ 500 g/d with <100 g/d of total vegetable intake, the multivariable-adjusted RR for total cancer incidence was 0.72 (95% CI: 0.58, 0.90; P-trend: 0.02; P-nonlinearity: 0.06). For total cancer mortality, the multivariable-adjusted RRs comparing 100 to <200 g/d, 200 to <300 g/d, 300 to <500 g/d, and ≥ 500 g/d with <100 g/d of total vegetable intake were 0.68 (95% CI: 0.53, 0.88), 0.75 (95% CI: 0.57, 0.98), 0.72 (95% CI: 0.54, 0.95), and 0.67 (95% CI: 0.47, 0.95), respectively (P-trend: 0.09; P-nonlinearity: 0.01). No associations were found between total fruit intake and total cancer incidence and mortality; ≥ 300 g/d vs. <50 g/d, RR: 1.04 (95% CI: 0.87, 1.25; P-trend = 0.56) for incidence and RR: 0.89 (95% CI: 0.66, 1.21; P-trend = 0.71) for mortality. CONCLUSIONS: Our findings suggest that total vegetable intake is linearly associated with cancer incidence but nonlinearly associated with total cancer mortality in middle-aged Korean men. However, total fruit intake is not associated with total cancer incidence or mortality.


Assuntos
Povo Asiático , Neoplasias/epidemiologia , Neoplasias/mortalidade , Verduras , Adulto , Frutas , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Modelos de Riscos Proporcionais , Estudos Prospectivos , República da Coreia , Fatores de Risco , Inquéritos e Questionários
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