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排序方式: 共有328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
2.
Kohji Matsushita Kazuo Kitagawa Tomohiro Matsuyama Toshiho Ohtsuki Akihiko Taguchi Kenji Mandai Takuma Mabuchi Yoshiki Yagita Takehiko Yanagihara Masayasu Matsumoto 《Brain research》1996,743(1-2)
The divalent cation zinc has been reported to possess several physiological properties such as blocking apoptotic cell death through an inhibitory effect on Ca2+-Mg2+ endonuclease activity, or modulating the neurotoxicity via glutamate receptor subtypes. In the present study, we investigated the effect of peripherally injected zinc on delayed neuronal death seen in the hippocampus after transient global ischemia, in order to elucidate a possible beneficial role on zinc in ischemic neuronal cell death. Forty-five adult Mongolian gerbils of both sexes underwent transient bilateral clipping of the common carotid arteries for 3 min. In the pretreated animals, ZnCl2 (20 mg/kg) was injected subcutaneously once, 1 h before ischemia (superacute group; n=6) or twice at 24 and 48 h before ischemia (subacute group; n=14). Histological survey was carried out 3 days later by in situ DNA fragmentation method and 4 days later by hematoxylin-eosin staining by semiquantatively counting dead neurons in the CA1 sector. Subacute zinc pre-administration significantly reduced the nuclear damage and subsequent neuronal death; however, superacutely pre-administered zinc did not protect hippocampal neurons against ischemia but it did not aggravate the effect of ischemia, either. The present study suggested that transfer of exogenous zinc into the intracellular space is required for neuroprotection, presumably via the anti-endonuclease activity. 相似文献
3.
产青霉素酶淋病奈瑟球菌耐药质粒的提取与酶切分析 总被引:1,自引:1,他引:0
目的 了解产青霉素酶淋病奈瑟球菌(PPNG)在本地区的分布状况及其耐药质粒的限制性核酸内切酶长度多态性分析。方法 用碘量法筛选PPNG株,碱变性法进行质粒抽提,回收7.4kb及5.4kb质粒进行酶切分析。结果 68株临床分离株筛选出PPNG菌3株,经限制性核酸内切酶长度多态性分析,PPNG菌7、4kb及5.4kb质粒含有BamHⅠ的双酶切位点,7.4kb质粒含有PstⅠ及HindⅡ单酶切位点。结论 PPNG菌株的筛选及耐药质粒的酶切分析为追踪耐药菌株的流行趋势提供了流行病学信息。 相似文献
4.
卡那霉素链霉菌温和性噬菌体SKJ1DNA上有2个AvaI和SmaI酶切位点,8个SalI位点,7个EcoRI位点及12个BamHI位点,经酶切后用1%琼脂糖凝胶电泳测定SKJ1DNA大小为60.7kb。用单酶切,双酶切及片段酶切分析,得到SKJ1DNA的AvaI、SmaI、EcoRI、SalI酶切图谱及BamI1的部分酶切图谱,证明AvaI和SmaI在SKJ1DNA上具有相同酶切位点,并经过酶切结 相似文献
5.
流行性乙型脑炎病毒结构蛋白编码基因的重组构建 总被引:1,自引:1,他引:0
目的:建立流行性乙型脑炎病毒(JEV)C、prME,E等结构蛋白编码基因克隆.方法:病毒感染C6/36细胞,RT-PCR法依次获取该病毒结构蛋白基因并进行DNA测序分析,PCR克隆法将PCR产物分别构建于真核表达载体pcDNA 3.1的BamHI与EcoRI酶切位点并依次命名为pJC、pJME与pJE,通过DNA测序、电泳以及限制性内切酶分析加以鉴定.结果:JEV C、prME与E基因片段分别为380、2001以及1 500bp,各基因测序结果与发表的JEV JaGAr-01株相对应序列相一致,从重组质粒释出的插入子分别与各基因大小相符合.结论:pJC、pJME与pJE重组质粒分别含有C、prME与E蛋白编码基因. 相似文献
6.
Restriction endonuclease analysis of varicella-zoster vaccine virus and wild-type DNAs 总被引:9,自引:0,他引:9
The DNA from several clinical isolates of varicella-zoster virus (VZV) were compared with the DNA from the vaccine strain VZV using three restriction endonucleases: BamHI, BgII, and HpaI. When electrophoresed through an agarose gel, the vaccine DNA digestion pattern was significantly different from the digestion patterns of the wild-type DNAs. Variations in the digestion pattern of the separate clinical isolates were also observed. 相似文献
7.
DNA cloned from the ayw subtype of hepatitis B virus 总被引:4,自引:0,他引:4
DNA from the ayw subtype of hepatitis B virus (HBV) was ligated into the EcorI site of DNA from plasmid pBR322 and propagated in E coli chi 776. A plasmid with a 3200 base pair insert (pHBV-1) was isolated and the cloned HBV DNA was mapped with restriction endonucleases. Differences were found in restriction endonuclease cleavage sites for DNAs from HBV of subtype ayw and adr. 相似文献
8.
DNA from Molluscum contagiosum virus (MCV) isolates was analysed by restriction endonuclease digestion, identifying three virus subtypes. The structural features of MCV DNA are typical of poxviral DNA. Physical maps of cleavage sites for BamHI, CIaI, and HindIII were constructed for single isolates of each subtype. These differ extensively, indicating the independence of the three subtypes. However, they are closely related, as determined by molecular hybridisation and nucleotide sequence analysis, and their genomes are essentially colinear. There is marked geographical variation in the relative incidence of MCV I and II, whilst MCV III is uniformly rare. 相似文献
9.
Restriction fragment differences between the genomes of the Oka varicella vaccine virus and American wild-type varicella-zoster virus 总被引:5,自引:0,他引:5
The Oka vaccine strains of varicella-zoster virus (VZV) have a significantly different BgII DNA restriction pattern from that of American wild-type isolates of VZV. This difference consists primarily of an additional BgII site, which lies within the BamHI "D" fragment. In conjunction with a study of the efficacy of an experimental Merck/Oka VZV vaccine, the area of the genome from which the most marked restriction pattern alteration arises was studied more closely to determine if there are other significant differences between the Oka strains and American wild-type strains. BamHI "D" fragments from the DNA of the Oka parent strain (the progenitor of the vaccine strain), the RIT/Oka vaccine strain (a derivative of the Oka parent strain), the Merck/Oka vaccine strain, and the EF strain (an American wild type), were submitted to extensive endonuclease digestion studies to ascertain if additional unique restriction sites are present in the Oka parent or vaccine strains. The extra BgII restriction site characteristic of the Merck/Oka vaccine strain is also present in the DNA of the parent virus as well as its derivatives and was therefore not produced by the "attenuation" process. No other novel sites were found in the Oka parent or Oka-derived strains in this section of the genome. The Merck/Oka vaccine strain of VZV, despite its Japanese origin, is therefore quite similar to circulating American varicella-zoster virus strains. Varicella-zoster virus DNA, at least in the area of the BamHI D fragment, also appears to be remarkably stable from strain to strain. 相似文献
10.
Uehara S Tamura M Nata M Ji G Yaegashi N Okamura K Yajima A 《Journal of human genetics》2000,45(3):119-126