Juvenile visceral steatosis (jvs) mice, isolated from the C3H-H-2 degrees strain, exibit a systemic carnitine deficiency (SCD) phenotype and develop fatty liver, hyperammonemia and hypoglycemia. This phenotype is caused by a missense mutation (Leu352Arg) of a sodium-dependent carnitine/organic cation transporter, Octn2 (Slc22a5). The jvs mouse could be a useful model for pharmacokinetics and drug metabolism studies concerning Octn2 substrate drugs. In the present study, the effects of the SCD phenotype on the cytochrome P450 (P450 or CYP) dependent activities of four endobiotic and seven xenobiotic oxidations catalyzed by liver and kidney microsomes from jvs mice were investigated. The jvs-type mutation was genotyped by PCR-RFLP. The contents of total P450 and NADPH-P450 reductase were similar in the the liver microsomes from male or female mice of the wild-type and those heterozygous or homozygous for the jvs-type mutation. The 6beta-hydroxylation activities of testosterone and progesterone (marker for Cyp3a) based on the protein contents were 1.2- to 2.0-fold higher in liver microsomes from jvs/jvs-type mice compared to jvs/wt- or wt/wt-type mice. Coumarin 7-hydroxylation activities (marker for Cyp2a) were decreased to 0.7-fold in the male jvs/jvs-type mice. The activities of lauric acid 12-hydroxylation (a marker for Cyp4a) and aniline p-hydroxylation (a marker for Cyp2e1) in liver microsomes were increased 1.4- to 1.9-fold in female jvs/jvs-type mice. Genotoxic activation of 2-aminofluorene (a marker for Cyp4b1) by male and female mouse kidney microsomes were not affected by the SCD phenotype. These results demonstrated that the SCD phenotype affected the P450-dependent catalytic activities in liver microsomes. The jvs mouse could provide valuable information in drug interaction and drug metabolism studies of OCTN2 substrate drugs and new compounds in development.
1.Introduction The searches for positive electrode materials with high capacity for Li-ion secondary batteries have been extensively investigated. Recently, it has been reported that anion redox, oxygen plays a redox reaction in Li-excessive positive materials such as Li2MnO3[1] or Li3NbO4[2], lead to high capacity. We have focused on α-LiAlO2 which is expected to have layered rock-salt structure in order to examine the possibility for oxide ions in lithium metal oxides to participate in the electrochemical reaction. Although no transition metals are included in this compound, the electrochemical activity as a positive electrode has been predicted by ab-initio calculation[3]. However, the experimental property itself is not well understood due to the difficulties of the synthesis. The objective of our study is to obtain a single α phase with high crystallinity and to reveal the electrochemical properties of the samples. 2.Experimental We adopted sol-gel method to obtain single α phase. LiNO3 and Al(NO3)3·9H2O were used for the starting materials. They were dissolved in an ethanol solution with vinylpyrrolidone(VP) or polyvinylpyrrolidone(PVP)(K = 30, 90) ( K denotes a characteristic viscosity involving molecular weight ) and without anything for comparison. After stirring the solution at room temperature for 24 h, it was dried at 368 K for 96 h until the solution transformed gel-like state. Then, it was calcinationed at 773 K for 12 h and heated at 973 or 1023K for 12 h. The powder X-ray diffraction measurement by CuKα radiation was performed to identify the crystalline phase. Structural refinements were carried out by Rietveld analysis using the RIETAN-FP program. Ionic conductivity was calculated from impedance spectroscopy performed at an applied voltage of 10 mV in the frequency range from 1 MHz to 100 mHz. Electrochemical testing was carried out with samples / 1M LiPF6 in EC : DMC(1:1) / Li or samples / Li10GeP2S12 / In-Li. The respective positive electrode was composed of the following materials; specimen : acetylene black : PTFE = 80:15:5 (wt.%) or specimen : acetylene black : NMP = 86 : 7 : 7. The current densities were 4.5 μA / cm2 or 1.6 μA / cm2 in the range of 2.5-4.8 V and 1.4-.6.0V. 3.Results The solid phase method and the sol-gel method using VP or without anything produced a large quantify of γ phase. The single α phase was obtained by the sol-gel method using PVP (K = 30, 90). Although PVP is decomposed during calcination, we clarified that the presence and molecular chain length of PVP have a great influence on generating α single phase. By the Rietveld analysis, it was confirmed that the crystal structure of the obtained α phase is layered rock-salt structure, same as LiCoO2. At the same time, we confirmed the occupancy of each site. We researched about electrochemical properties of obtained samples. The calculated ionic conductivity is about 10-7Scm-1 at room temperature, which is much higher than the reported value, 10-21Scm-1[4]. However, the activity of the sample was as low as 10 mAhg-1 in the charge-discharge measurement using the electrolyte. This is because that α-LiAlO2 has a large bandgap and expected reaction voltage is high over 5V. Therefore, we attempted measurement at high voltage above 5V using a solid electrolyte. Then, the charge capacity improved to about 35mAhg-1. From the above results, it was difficult to obtain a large capacity by itself. So, we investigated the coexistence effect of α-LiAlO2 with other active materials. When mixed with LiCoO2, the charge capacity was larger than the capacity depending on the LiCoO2 content. A plateau was seen around 4.6V, similar to what has been confirmed in other reported systems of oxygen reactions. The electrochemical activity of α-LiAlO2 may induced by composite with LiCoO2. 4.References [1] M. Oishi, et al., J. Mater. Chem. A, 4(2016)9293–9302. [2] N. Yabuuchi, et al., PNAS., 112(2015)7650. [3] G. Ceder, et al., Nature., 392(1998)694-696. [4] Jian Gao, et al., Solid State Ionics., 286(2016)122-134.
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