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排序方式: 共有3278条查询结果,搜索用时 15 毫秒
1.
Hiroki Koshimichi Yoshiyuki Tsuda Toru Ishibashi Toshihiro Wajima 《Journal of pharmaceutical sciences》2019,108(5):1896-1904
Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships. Population pharmacokinetic analysis of the baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer. A 2-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing the clearance and distribution volume. A dose regimen based on the body weight (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race; however, the exposures were dependent on the body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups. In conclusion, the population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid. 相似文献
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S-100 is a calcium-binding, glial protein which has been shown to be involved in behavioral learning and memory tasks. Long-term potentiation (LTP) in the hippocampus is a long-lasting enhancement of synaptic efficacy evoked by repetitive afferent stimulation. When anti-S-100 serum is applied by pressure ejection onto the stratum radiatum of area CA1 of the hippocampal slice, the amplitude of the extracellularly recorded population spike is not affected. However, repetitive stimulation of the afferents during S-100 application failed to produce LTP. At a distant site in the same slice, LTP occurs normally. Preimmune normal rabbit serum had no effect on the development of LTP. It appears that S-100 protein is involved in the establishment of LTP. 相似文献
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目的 观察大鼠全脑不同剂量照射后1月内不同时间点血清中S-100B的变化,以探讨S-100OB在早期放射性脑损伤中的变化特征.方法 对大鼠予4 MeV电子线分别单次全脑照射2、10和30 Gv制备大鼠早期放射性脑损伤模型.采用酶联免疫吸附试验(ELISA)检测照射后1 h、6 h、12 h、24 h、3 d、1周、1个月血清中S-100B的浓度.结果 大鼠血清S-100B浓度在照射后6 h升高最明显,照射后12 h浓度下降,照后24 h再升高(除外2 Gy组为在照射后3 dR升高),随后下降直到最后观察时间点.结论 大鼠全脑照射后血清S-100B水平发生了变化,不同剂量组血清S-100B浓度有显著性差异,剂最越高,浓度越高.结果 提示S-100B可能会成为检测早期放射性脑损伤的重要血清指标. 相似文献
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A series of 237 appendices was studied immunohistochemically for neurogenous hyperplasia. This was observed in 195 cases. It was possible to trace a continuum from appendices with intact lumens, featuring intramucosal neurogenous hyperplasia often with co-existent submucosal and muscular nerve growth, to obliterated specimens whose axial portions were composed of varying proportions of nerve tangles and fibrous tissue. Predominantly fibrotic specimens were considered as end-stages of this process. Stromal, argyrophilic cells lying amidst the nerve elements were prominent in the early, non-obliterated cases; their number decreased in the obliterated nerve rich specimens and such cells became inapparent in the late fibrotic stage. Repeated minimal subclinical attacks of inflammation are thought to trigger this lesion. 相似文献
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Lorraine D. Buckberry Ian S. Blagbrough Barrie W. Bycroft P.Nicholas Shaw 《Toxicology letters》1992,60(3):241-246
The C-S lyase enzymes are responsible for the generation of mutagenic and cytotoxic metabolites via aberrant drug-metabolising pathways in mammalian tissues. We have examined human hepatic cytosolic, mitochondrial and microsomal fractions for evidence of C-S lyase activity. The cytosolic enzyme was purified using fast protein liquid chromatography over FFQ Sepharose, Mono P and Superose 12. An homogeneous protein (monitored by SDS-PAGE) was obtained following purification, and an 11-fold increase in C-S lyase specific activity was observed. The molecular weight of the enzyme was found to be 37 kDa in denaturing conditions, 82.3 kDa in non-denaturing conditions, and the C-S lyase activity was shown to co-purify with kynurenine aminotransferase activity when the transaminase activity of the enzyme was examined with kynurenine as the substrate. 相似文献
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新生儿脑病S-100蛋白监测与预后的研究进展 总被引:1,自引:0,他引:1
目的:通过监测新生儿缺氧缺血性脑病(HIE)患儿血清中S-100蛋白含量的动态变化,建立对HIE患儿的早期科学诊断及预后评估技术指标。并探讨S-100蛋白浓度变化与病情的严重程度及转归之间的关系。方法:采用酶联免疫吸附试验、双抗体夹心法检测,对120例HIE有症状组患儿(HIE轻度症状组40例,HIE中度症状组40例,HIE重度症状组40例)和40例新生儿窒息组患儿与40例对照组健康新生儿血清S-100蛋白含量进行检测,并进行动态观察。结果:①HIE有症状组不同时期血清S-100蛋白含量均显著高于对照组(P<0.01);②新生儿窒息组不同时期的血清S-100蛋白含量也明显高于对照组(P<0.01);③HIE有症状组血清S-100蛋白含量明显高于新生儿窒息组(P<0.05)。结论:HIE有症状组患儿病情越重,其血清S-100蛋白含量则越高,提示血清S-100蛋白可作为判断HIE病情程度的客观依据和早期诊断以及预后评估HIE的主要指标。 相似文献
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本文采用S-100蛋白为免疫学标记,对34例恶性肿瘤局部淋巴结内树突状细胞进行免疫组化定量研究。结果按S-100蛋白阳性细胞数目多少分为增多(7例)、减少(20例)及正常(7例)3组,统计学分析增多组均值(164.4个/mm^2)明显高于对照组(58.3个/mm^2);减少组均值(16.5个/mm^2)组显低于对照组;而正常组均值(69.8个/mm^2)与对照组无显著差异。 相似文献
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