TY  - JOUR
A1  - Scheer, Nico
A1  - Kapelyukh, Yury
A1  - Rode, Anja
A1  - Buechel, Sandra
A1  - Wolf, C. Roland
T1  - Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines
JF  - Molecular Pharmacology
N2  - Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.
Y1  - 2012
U6  - https://doi.org/10.1124/mol.112.080036
SN  - 1521-0111
VL  - 82
IS  - 6
SP  - 1022
EP  - 1029
PB  - ASPET
CY  - Bethesda, Md.
ER  - 
TY  - CHAP
A1  - Nötzold, K.
A1  - Uphues, A.
A1  - Wegener, R.
A1  - Soter, S.
A1  - Fink, K.
A1  - Bragard, Michael
A1  - Griessel, R.
T1  - Inverter based test setup for LVRT verification of a full-scale 2 MW wind power converter
T2  - EPE Joint Wind Energy and T&D Chapters Seminar : 28th and 29th of June 2012, in the Utzon Centre, Aalborg, Denmark ; papers, posters, presentations. - Session 2: Grid connection, compliance
Y1  - 2012
PB  - EPE Association
CY  - Brussels
ER  - 
TY  - GEN
A1  - Frauenrath, Tobias
A1  - Fuchs, Katharina
A1  - Hezel, Fabian
A1  - Dieringer, Matthias A.
A1  - Rieger, Jan
A1  - Niendorf, Thoralf
T1  - Improved cardiac triggering by combining multiple physiological signals: a cardiac MR feasibility study at 7.0 T
T2  - 2012 ISMRM Annual Meeting Proceedings
N2  - In current clinical cardiovascular MR (CMR) practice cardiac motion is commonly dealt with using ECG based synchronization. However, ECG is corrupted by magneto-hydrodynamic (MHD) effects in magnetic fields. This leads to artifacts in the ECG trace and evokes severe T-wave elevations, which might be misinterpreted as R-waves resulting in erroneous triggering. At (ultra)high field strengths, the propensity of ECG recordings to MHD effects is further pronounced. Pulse oximetry (POX) being inherently sensitive to blood oxygenation provides an alternative approach for cardiac gating. However, due to the travel time of the blood the peak of maximum oxygenation and hence the trigger is delayed by approx. 300 ms with respect to the ECG's R-wave. Also the peak of maximum oxygenation shows a jitter of up to 65 ms. Alternative triggering approaches include acoustic cardiac triggering (ACT). In current clinical practice cardiac gating / triggering commonly relies on using single physiological signals only. Realizing this limitation this study proposes a combined triggering approach which exploits multiple physiological signals including ECG, POX or ACT to track cardiac activity. The feasibility of the coupled approach is examined for LV function assessment at 7.0 T. For this purpose, breath-held 2D-CINE imaging in conjunction with cardiac synchronization was performed paralleled by real time logging of physiological waveforms to track (mis)synchronization between the cardiac cycle and data acquisition. Combinations of the ECG, POX and ACT signals were evaluated and processed in real time to facilitate reliable trigger information.
Y1  - 2012
SN  - 1545-4428
N1  - ISMRM 20th Annual Meeting & Exhibition, 5-11 May 2012, Melbourne, Australia
ER  -