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排序方式: 共有399条查询结果,搜索用时 15 毫秒
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Kristini K Miles Stephan T Stern Philip C Smith Fay K Kessler Shazia Ali Joseph K Ritter 《Drug metabolism and disposition》2005,33(10):1513-1520
Mycophenolic acid (MPA; 1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzylfuranyl)-4-methyl-4-hexenoate), the active metabolite of the immunosuppressant prodrug, mycophenolate mofetil, undergoes glucuronidation to its 7-O-glucuronide as a primary route of metabolism. Because differences in glucuronidation may influence the efficacy and/or toxicity of MPA, we investigated the MPA UDP-glucuronosyltransferase (UGT) activities of human liver microsomes (HLMs) and rat liver microsomes with the goal of identifying UGTs responsible for MPA catalysis. HLMs (n = 23) exhibited higher average MPA glucuronidation rates (14.7 versus 6.0 nmol/mg/min, respectively, p < 0.001) and higher apparent affinity for MPA (K(m) = 0.082 mM versus 0.20 mM, p < 0.001) compared with rat liver microsomes. MPA UGT activities were reduced >80% in liver microsomes from Gunn rats. To identify the active enzymes, human and rat UGT1A enzymes were screened for MPA-glucuronidating activity. UGT1A9 was the only human liver-expressed UGT1A enzyme with significant activity and exhibited both high affinity (K(m) = 0.077 mM) and high activity (V(max) = 28 nmol x min(-1) x mg(-1)). Spearman correlation analyses revealed a stronger relationship between HLM MPA UGT activities and 1A9-like content (r(2) = 0.79) relative to 1A1 (r(2) = 0.20), 1A4-like (r(2) = 0.22), and 1A6 (r(2) = 0.41) protein. A different profile was observed for rat with three active liver-expressed UGT1A enzymes: 1A1 (medium affinity/capacity), 1A6 (low affinity/medium capacity), and 1A7 (high affinity/capacity). Our data suggest that UGT1A enzymes are the major contributors to hepatic MPA metabolism in both species, but 1A9 is dominant in human, whereas 1A1 and 1A7 are likely the principal mediators in control rat liver. This information should be useful for interpretation of MPA pharmacokinetic and toxicity data in clinical and animal studies. 相似文献
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Muhammad Irfan Irshad Ahmad Shazia Shukrullah Humaira Hussain Muhammad Atif Stanislaw Legutko Jana Petru Michal Hatala Muhammad Yasin Naz Saifur Rahman 《Materials》2022,15(13)
The development of cost-effective co-catalysts of high photocatalytic activity and recyclability is still a challenge in the energy transformation domain. In this study, 0D/2D Schottky heterojunctions, consisting of 0D ZnO and 2D Ti3C2, were successfully synthesized by the electrostatic self-assembling of ZnO nanoparticles on Ti3C2 nanosheets. In constructing these heterojunctions, Ti3C2 nanosheets acted as a co-catalyst for enhancing the transfer of excitons and their separation to support the photocatalytic response of ZnO. The as-prepared ZnO/Ti3C2 composites demonstrate an abbreviated charge transit channel, a huge interfacial contact area and the interfacial electrons’ transport potential. The extended optical response and large reactive area of the ZnO/Ti3C2 composite promoted the formation of excitons and reactive sites on the photocatalyst’s surface. The ZnO/Ti3C2 Schottky heterojunction showed significantly high photocatalytic activity for hydrogen production from a water–ethanol solution under the light illumination in the visible region. The hydrogen evolution overoptimized the ZnO/Ti3C2 composition with 30 wt.% of Ti3C2, which was eight times higher than the pristine ZnO. These findings can be helpful in developing 0D/2D heterojunction systems for photocatalytic applications by utilizing Ti3C2 as a low-cost co-catalyst. 相似文献
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Gadolinium for hysterosalpingography 总被引:1,自引:0,他引:1
OBJECTIVE: To evaluate the use of gadolinium as an alternative to iodinated contrast medium for hysterosalpingography in patients with an increased risk for iodinated contrast hypersensitivity. STUDY DESIGN: Between March 2003 and March 2006, 3,616 hysterosalpingography examinations were performed. Hysterosalpingography was routinely performed using water-soluble, nonionic, iodinated contrast medium. Hysterosalpingography was performed with gadolinium in patients at risk for contrast hypersensitivity. We retrospectively reviewed the diagnostic quality, safety and clinical outcome in patients who underwent gadolinium hysterosalpingography. RESULTS: Hysterosalpingograms of diagnostic quality were successfully performed without adverse reactions in 11 patients. The density of gadolinium contrast opacification was diminished as compared with a conventional hysterosalpingogram with iodinated contrast. Two of the 8 patients who were not on oral contraceptives and had patent fallopian tubes became pregnant within 6 months of the hysterosalpingogram procedure. CONCLUSION: Gadolinium hysterosalpingography is of diagnostic value and is a safe alternative to iodinated contrast medium for hysterosalpingography in patients at increased risk for iodinated contrast hypersensitivity. 相似文献
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David Lowe Shazia Shabir John Buckels Paolo Muiesan Geoffrey Hayden Andrew Holt Ahmed Hamsho Kassi Skordilis Graham Lipkin Richard Borrows David Briggs 《Transplant immunology》2014,30(1):30-33
This case report confirms the utility of simultaneous liver transplantation in allowing successful kidney transplantation in the face of preformed, high levels of DSA, which would under normal circumstances be associated with hyperacute rejection and kidney graft failure. Antibody characterisation in terms of epitope specificity is more accurate and informative than antibodies described as “antigen-specific” and we suggest a method for identifying and tracking these antibodies; i.e. follow the epitope reaction not the antigen reactions. We consider that this will give a better insight into the behaviour and pathogenicity of HLA-specific sera. In the case presented here this approach has revealed some novel features of the post transplant antibody response in a sensitised recipient. These illustrate three phenomena which challenge current dogmas; an early resynthesis of DSA does not necessarily cause AMR, high levels of DSA can spontaneously modulate, and measurement of antibodies in terms of antigen specificity can give misleading results. 相似文献
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Lydia Lacerda Joy McCarthy Shazia F. K. Mungly Edward G. Lynn Michael N. Sack Lionel H. Opie Sandrine Lecour 《Basic research in cardiology》2010,105(6):751-762
Our novel proposal is that TNFα exerts a direct effect on mitochondrial respiratory function in the heart, independently of
its cell surface receptors. TNFα-induced cardioprotection is known to involve reactive oxygen species (ROS) and sphingolipids.
We therefore further propose that this direct mitochondrial effect is mediated via ROS and sphingolipids. The protective concentration
of TNFα (0.5 ng/ml) was added to isolated heart mitochondria from black 6 × 129 mice (WT) and double TNF receptor knockout
mice (TNFR1&2−/−). Respiratory parameters and inner mitochondrial membrane potential were analyzed in the presence/absence of two antioxidants,
N-acetyl-l-cysteine or N-tert-butyl-α-(2-sulfophenyl)nitrone or two antagonists of the sphingolipid pathway, N-oleoylethanolamine (NOE) or imipramine. In WT, TNFα reduced State 3 respiration from 279.3 ± 3 to 119.3 ± 2 (nmol O2/mg protein/min), increased proton leak from 15.7 ± 0.6% (control) to 36.6 ± 4.4%, and decreased membrane potential by 20.5 ± 3.1%
compared to control groups. In TNFR1&2−/− mice, TNFα reduced State 3 respiration from 205.2 ± 4 to 75.7 ± 1 (p < 0.05 vs. respective control). In WT mice, both antioxidants added with TNFα restored State 3 respiration to 269.2 ± 2 and
257.6 ± 2, respectively. Imipramine and NOE also restored State 3 respiration to 248.4 ± 2 and 249.0 ± 2, respectively (p < 0.01 vs. TNFα alone). Similarly, both antioxidant and inhibitors of the sphingolipid pathway restored the proton leak to
pre-TNF values. TNFα-treated mitochondria or isolated cardiac muscle fibers showed an increase in respiration after anoxia–reoxygenation,
but this effect was lost in the presence of an antioxidant or NOE. Similar data were obtained in TNFR1&2−/− mice. TNFα exerts a protective effect on respiratory function in isolated mitochondria subjected to an anoxia–reoxygenation
insult. This effect appears to be independent of its cell surface receptors, but is likely to be mediated by ROS and sphingolipids. 相似文献