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151.
Selenium has a protective role in caspase-3-dependent apoptosis induced by H2O2 in primary cultured pig thyrocytes 总被引:6,自引:0,他引:6
Demelash A Karlsson JO Nilsson M Björkman U 《European journal of endocrinology / European Federation of Endocrine Societies》2004,150(6):841-849
OBJECTIVE: Hydrogen peroxide (H2O2), necessary for thyroid hormonogenesis, is produced at the apical surface of the thyroid follicular epithelium. Excess H2O2 is potentially cytotoxic and may contribute to the development of hypothyroidism, e.g. in severe selenium deficiency. Yet it is unclear how H2O2 contributes to thyroid cell death. DESIGN AND METHODS: H2O2-induced apoptosis and necrosis were studied in primary cultured pig thyroid cells. Glutathione peroxidase (GPx) activity was altered by culture in low serum with or without selenite substitution. Apoptosis was evaluated by spectrofluorometric measurement of caspase-3-specific substrate cleavage, and by analysis of DNA fragmentation by agarose gel electrophoresis. Necrosis was detected by 51Cr release from prelabeled cells. RESULTS: Exogenous H2O2 dose-dependently (100-400 micromol/l) activated caspase-3 within 3-12 h, and DNA degradation was observed after 24 h. The potency of H2O2 to induce apoptosis was low compared with that of staurosporine, a strong proapoptotic agent. H2O2-treated cells with reduced GPx activity showed increased caspase-3 activation. Incubation of serum-starved cells with selenite (10-100 nmol/l) normalized the GPx activity and reduced the activation of caspase-3 by H2O2. High H2O2 concentrations (400-800 micromol/l) were required to obtain necrosis. The H2O2-induced necrosis was exaggerated by both low GPx activity and catalase inhibition. CONCLUSIONS: Cytotoxic effects of H2O2 on thyroid cells include caspase-3-dependent apoptosis that occurs at H2O2 concentrations insufficient to induce necrosis. Selenium deficiency aggravates the apoptotic response, probably due to impaired capacity of GPx to degrade H2O2. 相似文献
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Rody El Nawar Bertrand Lapergue Michel Piotin Benjamin Gory Raphael Blanc Arturo Consoli Georges Rodesch Mikael Mazighi Frederic Bourdain Maéva Kyheng Julien Labreuche Fernando Pico 《JACC: Cardiovascular Interventions》2019,12(4):385-391
Objectives
The aim of this study was to determine whether individual operator characteristics have an impact on reperfusion and procedural complication rates.Background
Mechanical thrombectomy (MT) is a Level IA treatment in acute ischemic stroke (AIS) patients. The operator’s effect has been found to be an independent predictor for clinical outcome and technical performance in interventional cardiology.Methods
From the ETIS (Endovascular Treatment in Ischemic Stroke) study, a prospective, multicenter, observational real-world MT registry, the authors included all AIS patients consecutively treated by MT between January 2012 and March 2017 in 3 high-volume comprehensive stroke centers by 19 operators. We assessed the effect of individual operator characteristics on successful reperfusion, defined as modified Thrombolysis In Cerebral Infarction 2b/3 at the end of MT, and procedural complications using multivariable hierarchical logistic regression models.Results
A total of 1,541 patients with anterior and posterior AIS were enrolled (mean age 67 years; median NIHSS 16). There was a significant operator effect on successful reperfusion, with an intraclass correlation coefficient of 0.036 (p = 0.046), but not on complications (intraclass correlation coefficient = 0). There was a dose–response relationship between annual operator volume and successful reperfusion rate (p = 0.003) with an adjusted odds ratio for successful reperfusion equal to 2.52 (95% confidence interval: 1.37 to 4.64) for patients treated by an operator with an annual volume ≥40 MT/year compared with those treated by an operator with <14 MT/year (first tertile). Nevertheless, this result did not translate to better clinical outcomes.Conclusions
Our data suggest that operator volume of MT/year has a positive impact on successful reperfusion in AIS patients, but not on clinical outcomes nor on complication rates. Further studies are warranted to investigate threshold procedure numbers associated with better outcomes. 相似文献154.
Katsiaryna S. Burts Tatiana V. Plisko Mikael Sjlin Goncalo Rodrigues Alexandr V. Bildyukevich Frank Lipnizki Mathias Ulbricht 《Materials》2022,15(1)
This study deals with the development of antifouling ultrafiltration membranes based on polysulfone (PSF) for wastewater treatment and the concentration and purification of hemicellulose and lignin in the pulp and paper industry. The efficient simple and reproducible technique of PSF membrane modification to increase antifouling performance by simultaneous addition of triblock copolymer polyethylene glycol-polypropylene glycol-polyethylene glycol (Synperonic F108, Mn =14 × 103 g mol−1) to the casting solution and addition of polyacrylic acid (PAA, Mn = 250 × 103 g mol−1) to the coagulation bath is proposed for the first time. The effect of the PAA concentration in the aqueous solution on the PSF/Synperonic F108 membrane structure, surface characteristics, performance, and antifouling stability was investigated. PAA concentrations were varied from 0.35 to 2.0 wt.%. Membrane composition, structure, and topology were investigated by Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and scanning electron microscopy (SEM). The addition of PAA into the coagulation bath was revealed to cause the formation of a thicker and denser selective layer with decreasing its pore size and porosity; according to the structural characterization, an interpolymer complex of the two additives was formed on the surface of the PSF membrane. Hydrophilicity of the membrane selective layer surface was shown to increase significantly. The selective layer surface charge was found to become more negative in comparison to the reference membrane. It was shown that PSF/Synperonic F108/PAA membranes are characterized by better antifouling performance in ultrafiltration of humic acid solution and thermomechanical pulp mill (ThMP) process water. Membrane modification with PAA results in higher ThMP process water flux, fouling recovery ratio, and hemicellulose and total lignin rejection compared to the reference PSF/Synperonic F108 membrane. This suggests the possibility of applying the developed membranes for hemicellulose concentration and purification. 相似文献
155.
Wenya Linda Bi Lakshmi Nayak David M Meredith Joseph Driver Ziming Du Samantha Hoffman Yvonne Li Eudocia Quant Lee Rameen Beroukhim Mikael Rinne Ricardo McFaline-Figueroa Ugonma Chukwueke Christine McCluskey Sarah Gaffey Andrew D Cherniack Jennifer Stefanik Lisa Doherty Christina Taubert Meghan Cifrino Deborah LaFrankie Thomas Graillon Patrick Y Wen Keith L Ligon Ossama Al-Mefty Raymond Y Huang Alona Muzikansky E Antonio Chiocca Sandro Santagata Ian F Dunn David A Reardon 《Neuro-oncology》2022,24(1):101
BackgroundProgrammed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy.MethodsTwenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor-infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale.ResultsEnrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected adverse events. Six-month progression-free survival (PFS-6) rate was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was >10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased posttreatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO.ConclusionNivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens. 相似文献
156.
Kee Thai Yeo Ju Lee Oei Daniele De Luca Georg M. Schmölzer Robert Guaran Pamela Palasanthiran Kishore Kumar Giuseppe Buonocore Jeanie Cheong Louise S. Owen Satoshi Kusuda Jennifer James Gina Lim Ankur Sharma Sabita Uthaya Christopher Gale Elizabeth Whittaker Cheryl Battersby Neena Modi Mikael Norman Lars Naver Eric Giannoni Yenge Diambomba Prakeshkumar S. Shah Luigi Gagliardi Michael Harrison Shakti Pillay Abdullah Alburaey Yuan Yuan Huayan Zhang 《Acta paediatrica (Oslo, Norway : 1992)》2020,109(11):2192-2207
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