@article{ErmolaevNivokovMelnikovaetal.2018, author = {Ermolaev, A.P. and Nivokov, I.A. and Melnikova, L.I. and Kotliar, Konstantin}, title = {Сравнительная характеристика химического состава витреального содержимого кадаверных глаз и глаз с рефрактерной терминальной глаукомой}, series = {Vestnik oftalmologii}, volume = {5}, journal = {Vestnik oftalmologii}, number = {2}, publisher = {Media Sfera}, address = {Moskau}, doi = {10.17116/oftalma2018134051195}, pages = {195 -- 201}, year = {2018}, abstract = {Purpose — to compare the chemical elemental composition of vitreous cavity content taken from cadaveric eyes compared to samples taken from the eyes with terminal stage refractory glaucoma with decompensated intraocular pressure (IOP). Material and methods. The vitreous contents of the eyes from 2 groups were studied. The 1st group included 15 cadaveric eyes; the 2nd group included 15 eyes with refractory glaucoma in the terminal stage of the disease with decompensated IOP in patients with hypertension pain. The vitreal content samples were taken in the course of antiglaucoma surgery aimed at preserving the eye as an organ and involving employment of drainage in the vitreous cavity. The study of virtual contents was carried out on energy dispersive spectrometer Oxford X-Max 50 integrated into scanning electron microscope Zeiss EVO LS10. Results. Increased concentrations of Kalium and Phosphorus were detected in the vitreous content of cadaveric eyes compared with the vitreal content from the eyes with terminal glaucoma with decompensated IOP taken in vivo (K — 0.172/0.093; P — 0.045/0.025 mmol/L). In the vitreous cavity in the eyes with end-stage glaucoma with decompensated IOP, the concentration of Nitrogen was higher in comparison with human cadaver eyes (2.030/1.424 mmol/L). Conclusion. The increased concentrations of Kalium and Phosphorus in the vitreous content of cadaveric eyes is associated with postmortem autolytic processes and with the release of intracellular content in the destruction of cell membranes. The increased Nitrogen concentration in the vitreal contents of the eyes with terminal stage glaucoma with decompensated IOP may be associated with the presence of osmotically active nitrogen-containing compounds in the eyes with increased IOP.}, language = {ru} } @article{Olbertz2018, author = {Olbertz, Klaus}, title = {{\"U}berwachung von Arbeitnehmern als Ausdruck von Compliance - Grunds{\"a}tze sowie Zul{\"a}ssigkeit und Grenzen einzelner Maßnahmen}, series = {NWB - Steuer- und Wirtschaftsrecht}, journal = {NWB - Steuer- und Wirtschaftsrecht}, number = {21}, publisher = {NWB-Verl.}, address = {Herne}, issn = {1860-9449}, pages = {1547 -- 1555}, year = {2018}, language = {de} } @article{Thomas2018, author = {Thomas, Axel}, title = {Zielerreichungen der Technologie- und Gr{\"u}nderzentren aus Sicht der kommunalen Finanzwirtschaft - dargestellt am Beispiel der Aachener Region}, series = {Der Gemeindehaushalt}, volume = {119}, journal = {Der Gemeindehaushalt}, number = {7}, publisher = {Kohlhammer}, address = {Stuttgart}, issn = {0340-3645}, pages = {149 -- 155}, year = {2018}, language = {de} } @article{HueningHeuermannWache2018, author = {H{\"u}ning, Felix and Heuermann, Holger and Wache, Franz-Josef}, title = {Wireless CAN without WLAN or Bluetooth}, series = {CAN Newsletter}, journal = {CAN Newsletter}, number = {December 2018}, pages = {44 -- 46}, year = {2018}, abstract = {In two developed concepts, dual-mode radio enables CAN participants to be integrated wirelessly into a CAN network. Constructed from a few components, a protocol-free, real-time transmission and thus transparent integration into CAN is provided.}, language = {en} } @article{HueningHeuermannWache2018, author = {H{\"u}ning, Felix and Heuermann, Holger and Wache, Franz-Josef}, title = {Wireless CAN}, series = {Etz: Elektrotechnik \& Automation}, volume = {139}, journal = {Etz: Elektrotechnik \& Automation}, number = {10}, publisher = {VDE-Verlag}, address = {Wuppertal}, issn = {0170-1711}, pages = {22 -- 26}, year = {2018}, abstract = {In modernen elektronischen und mechatronischen Systemen, z. B. im industriellen oder automobil Bereich, kommunizieren eingebettete Steuerger{\"a}te und Sensoren vielfach {\"u}ber Bussysteme wie CAN oder LIN. Die Kommunikation findet in der Regel drahtgebunden statt, so dass der Kabelbaum f{\"u}r die Kommunikation sehr groß werden kann. Daher ist es naheliegend, Leitungen und dazugeh{\"o}rige Stecker, z. B. f{\"u}r nicht-sicherheitskritische Komfortsysteme, einzusparen und diese durch gerichtete Funkstrecken f{\"u}r kurze Entfernungen zu ersetzen. Somit k{\"o}nnten Komponenten wie ECUs oder Sensoren kabel- und steckerlos in ein Bussystem integriert werden. Zudem ist eine einfache galvanische und mechanische Trennung zu erreichen. Funk{\"u}bertragung wird bei diesen Bussystemen derzeit nicht eingesetzt, da insbesondere die Echtzeitf{\"a}higkeit und die Robustheit der vorhandenen Funksysteme nicht den Anforderungen der Anwendungen entspricht. Zudem sind bestehende Funksysteme wie WLAN oder Bluetooth im Vergleich zur konventionellen Verkabelung teuer und es besteht hierbei die M{\"o}glichkeit, dass sie ausspioniert werden k{\"o}nnen und so sensible Daten entwendet werden k{\"o}nnen. In dieser Arbeit wird eine alternative Realisierung zu den bestehenden Funksystemen vorgestellt, die aus wenigen Komponenten aufzubauen ist. Es ist eine protokolllose, echtzeitf{\"a}hige {\"U}bertragung m{\"o}glich und somit die transparente Integration in ein Bussystem wie CAN.}, language = {de} } @article{JungMuellerStaat2018, author = {Jung, Alexander and M{\"u}ller, Wolfram and Staat, Manfred}, title = {Wind and fairness in ski jumping: A computer modelling analysis}, series = {Journal of Biomechanics}, journal = {Journal of Biomechanics}, number = {75}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0021-9290}, doi = {10.1016/j.jbiomech.2018.05.001}, pages = {147 -- 153}, year = {2018}, abstract = {Wind is closely associated with the discussion of fairness in ski jumping. To counter-act its influence on the jump length, the International Ski Federation (FIS) has introduced a wind compensation approach. We applied three differently accurate computer models of the flight phase with wind (M1, M2, and M3) to study the jump length effects of various wind scenarios. The previously used model M1 is accurate for wind blowing in direction of the flight path, but inaccuracies are to be expected for wind directions deviating from the tangent to the flight path. M2 considers the change of airflow direction, but it does not consider the associated change in the angle of attack of the skis which additionally modifies drag and lift area time functions. M3 predicts the length effect for all wind directions within the plane of the flight trajectory without any mathematical simplification. Prediction errors of M3 are determined only by the quality of the input data: wind velocity, drag and lift area functions, take-off velocity, and weight. For comparing the three models, drag and lift area functions of an optimized reference jump were used. Results obtained with M2, which is much easier to handle than M3, did not deviate noticeably when compared to predictions of the reference model M3. Therefore, we suggest to use M2 in future applications. A comparison of M2 predictions with the FIS wind compensation system showed substantial discrepancies, for instance: in the first flight phase, tailwind can increase jump length, and headwind can decrease it; this is opposite of what had been anticipated before and is not considered in the current wind compensation system in ski jumping.}, language = {en} } @article{Kurz2018, author = {Kurz, Melanie}, title = {Was heißt: Verantwortung im Design? Historische Positionen}, series = {Boxhorn: das Magazin aus dem Fachbereich Gestaltung der FH Aachen}, journal = {Boxhorn: das Magazin aus dem Fachbereich Gestaltung der FH Aachen}, number = {34}, address = {Aachen}, pages = {26 -- 33}, year = {2018}, language = {de} } @article{SchirraBissonnetteBramesfeld2018, author = {Schirra, Julian and Bissonnette, William and Bramesfeld, G{\"o}tz}, title = {Wake-model effects on induced drag prediction of staggered boxwings}, series = {Aerospace}, volume = {5}, journal = {Aerospace}, number = {1}, issn = {2226-4310}, doi = {10.3390/aerospace5010014}, year = {2018}, language = {en} } @article{KlockeRichertSube2018, author = {Klocke, Martina and Richert, Vera and Sube, Maike}, title = {Vier Jahre „Guter Studienstart im Ingenieurbereich": Entwicklung und Perspektiven des „Nullten Semesters" in Aachen}, series = {Zeitschrift f{\"u}r Beratung und Studium}, volume = {13}, journal = {Zeitschrift f{\"u}r Beratung und Studium}, number = {1}, publisher = {Universit{\"a}tsverlag Webler}, address = {Bielefeld}, issn = {1860-3068}, pages = {17 -- 22}, year = {2018}, abstract = {Bereits 2015 wurde in der Zeitschrift „Qualit{\"a}t in der Wissenschaft" (QiW) {\"u}ber das Kooperationsprojekt „Guter Studienstart im Ingenieurbereich", das Orientierungssemester von RWTH und FH Aachen, berichtet. In diesem Artikel legen wir den Schwerpunkt auf die Entwicklung des Projekts in den Jahren 2015 bis 2018 und geben eine R{\"u}ckschau sowie einen Ausblick auf die Entwicklungsperspektiven nach dem offiziellen Projektende.}, language = {de} } @article{ValeroBung2018, author = {Valero, Daniel and Bung, Daniel B.}, title = {Vectrino profiler spatial filtering for shear flows based on the mean velocity gradient equation}, series = {Journal of Hydraulic Engineering}, volume = {144}, journal = {Journal of Hydraulic Engineering}, number = {7}, publisher = {ASCE}, address = {Reston, Va.}, issn = {0733-9429}, doi = {10.1061/(ASCE)HY.1943-7900.0001485}, year = {2018}, abstract = {A new methodology is proposed to spatially filter acoustic Doppler velocimetry data from a Vectrino profiler based on the differential mean velocity equation. Lower and upper bounds are formulated in terms of physically based flow constraints. Practical implementation is discussed, and its application is tested against data gathered from an open-channel flow over a stepped macroroughness surface. The method has proven to detect outliers occurring all over the distance range sampled by the Vectrino profiler and has shown to remain applicable out of the region of validity of the velocity gradient equation. Finally, a statistical analysis suggests that physically obtained bounds are asymptotically representative.}, language = {en} } @article{ConzenAlbannaWeissetal.2018, author = {Conzen, Catharina and Albanna, Walid and Weiss, Miriam and K{\"u}rten, David and Vilser, Walthard and Kotliar, Konstantin and Z{\"a}ske, Charlotte and Clusmann, Hans and Schubert, Gerrit Alexander}, title = {Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes}, series = {Translational Stroke Research}, journal = {Translational Stroke Research}, number = {9}, publisher = {Springer Nature}, address = {Cham}, issn = {1868-601X}, doi = {10.1007/s12975-017-0585-8}, pages = {284 -- 293}, year = {2018}, abstract = {Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5-14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels—central retinal arteriolar and venular equivalent—was significantly reduced in the acute phase (p < 0.001) with gradual improvement in group B (p < 0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p < 0.001) and reduced area under the curve (p < 0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p < 0.05). Venous NVC was significantly delayed after SAH compared to group C (A p < 0.001; B p < 0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.}, language = {en} } @article{KotliarLanzl2018, author = {Kotliar, Konstantin and Lanzl, Ines}, title = {Vaskul{\"a}re Biomarker der retinalen Gef{\"a}βanalyse}, series = {Klinische Monatsbl{\"a}tter fur Augenheilkunde}, volume = {235}, journal = {Klinische Monatsbl{\"a}tter fur Augenheilkunde}, number = {12}, publisher = {Thieme}, address = {Stuttgart}, issn = {0023-2165}, doi = {10.1055/a-0774-7987}, pages = {1352 -- 1359}, year = {2018}, abstract = {Mit modernen nicht invasiven bildgebenden Verfahren lassen sich anhand der Fundusfotografie bzw. der optischen Verfilmung Aspekte der funktionellen und strukturellen retinalen Gef{\"a}ßver{\"a}nderungen objektiv untersuchen. Der Zustand und das Verhalten retinaler Gef{\"a}ße beeinflussen im pr{\"a}-, post- und kapillaren Bereich den Blutfluss und str{\"o}mungsbedingte Stoffwechselverh{\"a}ltnisse passiv und aktiv {\"u}ber den Gef{\"a}ßdurchmesser. Retinale Gef{\"a}ße gleichen von Aufbau und Funktion den zerebralen Gef{\"a}ßen und spiegeln den Zustand der Mikrozirkulation wider. Mithilfe von aus den Gef{\"a}ßweiten berechneten Biomarkern soll eine Aussage {\"u}ber die Prognose von systemischen vaskul{\"a}r bedingten Erkrankungen getroffen werden. Die statische retinale Gef{\"a}ßanalyse befasst sich mit der Untersuchung des Zustandes der pr{\"a}- und postkapillaren Gef{\"a}ßdurchmesser der retinalen Mikrozirkulation anhand einer optischen Fundusaufnahme. Bei der dynamischen retinalen Gef{\"a}ßanalyse wird der L{\"a}ngsschnitt eines retinalen Gef{\"a}ßes nicht invasiv funktionell und strukturell {\"u}ber einen Zeitraum vor, w{\"a}hrend und nach einer spezifischen vaskul{\"a}ren Stimulation untersucht. Die genaue Methodologie der Auswertung und die Bezeichnung der Parameter variieren bei unterschiedlichen Ans{\"a}tzen. Mittels retinaler Gef{\"a}ßanalyse wurden bislang mehrere klinische Querschnitts- und Interventionsstudien in der Augenheilkunde und anderen Fachgebieten, inkl. Kardiologie, Neurologie, Neurochirurgie, Nephrologie, Gyn{\"a}kologie, Sportmedizin, Diabetologie, Hypertensiologie usw. durchgef{\"u}hrt. Mit der statischen retinalen Gef{\"a}ßanalyse steht eine kosteng{\"u}nstige, reproduzierbare, nicht invasive Screeningtechnik zur Verf{\"u}gung, um eine prognostische Aussage {\"u}ber die Gef{\"a}ßgesundheit eines individuellen Patienten zu treffen. Die dynamische retinale Gef{\"a}ßanalyse besitzt ein weiteres diagnostisches Anwendungsspektrum als die statische, da sie das Verhalten retinaler Gef{\"a}ße zeitkontinuierlich untersucht. Die Evaluation vaskul{\"a}rer Erkrankungen sowie zerebro- bzw. kardiovaskul{\"a}rer Morbidit{\"a}t und Mortalit{\"a}t mittels mehrerer methodologischer Modalit{\"a}ten retinaler Gef{\"a}ßanalyse mit ihren jeweiligen quantitativen Biomarkern bietet eine zukunftstr{\"a}chtige diagnostische Perspektive. Die interdisziplin{\"a}re klinische Anwendung dieser vaskul{\"a}ren Biomarker gewinnt zunehmend an Bedeutung, sowohl in der Augenheilkunde als auch in anderen Fachgebieten.}, language = {de} } @article{RoethPielenWolffetal.2018, author = {R{\"o}th, Thilo and Pielen, Michael and Wolff, Klaus and L{\"u}diger, Thomas}, title = {Urbane Fahrzeugkonzepte f{\"u}r die Shared Mobility}, series = {Automobiltechnische Zeitschrift - ATZ}, volume = {120}, journal = {Automobiltechnische Zeitschrift - ATZ}, number = {1}, publisher = {Springer Vieweg}, address = {Wiesbaden}, issn = {0001-2785}, doi = {10.1007/s35148-017-0176-8}, pages = {18 -- 23}, year = {2018}, abstract = {Urbane Mobilit{\"a}tskonzepte der Zukunft erfordern neue Unternehmensformen, idealerweise aus Old Economy und New Economy, sowie eine enge Anbindung an die gesellschaftsrelevante Zukunftsforschung. F{\"u}r neue Fahrzeugkonzepte des Carsharing bedeutet dies, dass alle kostenverursachenden Faktoren erfasst und analysiert werden m{\"u}ssen. Die FH Aachen, share2drive und FEV geben einen Ausblick auf die zuk{\"u}nftige Fahrzeugklasse der Personal Public Vehicles als „Rolling Device".}, language = {de} } @article{KeutmannStaatLaack2018, author = {Keutmann, Sabine and Staat, Manfred and Laack, Walter van}, title = {Untersuchung der thermischen Auswirkung von therapeutischem Ultraschall}, volume = {7}, number = {10}, publisher = {Deutscher {\"A}rzte-Verl.}, address = {K{\"o}ln}, issn = {2193-5793}, pages = {518 -- 522}, year = {2018}, abstract = {Zusammenfassung: In der Orthop{\"a}die z{\"a}hlt der therapeutische Ultraschall als Mittel zur Pr{\"a}vention und Therapiebegleitung. Er hat mechanische, thermische und physiko-chemische Auswirkungen auf den menschlichen K{\"o}rper. Um mehr Erkenntnisse {\"u}ber die thermischen Auswirkungen zu erlangen, wurden Versuche an einem Hydrogel-Phantom und an Probanden durchgef{\"u}hrt. Dabei entstand eine signifikante Erw{\"a}rmung des Gewebes, welche beim Probandenversuch an der Oberfl{\"a}che und beim Hydrogelversuch in der Tiefe gemessen wurde. Summary: In orthopaedics, therapeutic ultrasound is a tool of prevention and therapy support. It has mechanical, thermal and physico-chemical effects on the human body. Tests with a hydrogel phantom and with human probands have been performed in order to obtain more knowledge about their thermal effects. Both tests measured temperature increases in cell tissue, on the surface with the human proband test and in depth with the hydrogel phantom test.}, language = {de} } @article{Golland2018, author = {Golland, Alexander}, title = {Umsetzung der Datenschutz-Grundverordnung - Neue Herausforderungen f{\"u}r Unternehmen}, series = {NWB Rechnungswesen - BBK}, journal = {NWB Rechnungswesen - BBK}, number = {1}, isbn = {0340-9848}, pages = {35 -- 39}, year = {2018}, abstract = {Nach einem intensiven politischen Diskurs wurde im vergangenen Jahr die Datenschutz-Grundverordnung (DSGVO) verabschiedet. Die DSGVO ersetzt zum 25.5.2018 die bislang geltende, aus dem Jahre 1995 stammende Datenschutz-Richtlinie 95/46/EG. Die Novellierung des Datenschutzrechts bringt zahlreiche neue Anforderungen mit sich. Unternehmen sind daher gezwungen, sich auf die {\"A}nderungen einzustellen, ihre datenschutzrelevanten Prozesse im Hinblick auf die neuen Anforderungen zu {\"u}berpr{\"u}fen und bis zum Mai 2018 an der DSGVO auszurichten. Der Beitrag gibt einen kurzen {\"U}berblick {\"u}ber die zentralen Aspekte der Datenschutzreform und die damit einhergehenden Herausforderungen f{\"u}r Unternehmen.}, language = {de} } @article{BergSchleserDelidovichetal.2018, author = {Berg, Alexander-Karl and Schleser, Markus and Delidovich, Artem and Houben, Alexander}, title = {Ultraschallunterst{\"u}tzter Schmelzklebstoffauftrag}, series = {adh{\"a}sion KLEBEN \& DICHTEN}, volume = {Volume 62}, journal = {adh{\"a}sion KLEBEN \& DICHTEN}, number = {Issue 12}, publisher = {Springer}, doi = {10.1007/s35145-018-0089-z}, pages = {32 -- 37}, year = {2018}, language = {de} } @article{Wollert2018, author = {Wollert, J{\"o}rg}, title = {TSN - Schluss mit dem Feldbuskrieg?}, series = {Design \& Elektronik}, journal = {Design \& Elektronik}, number = {3}, publisher = {WEKA-Fachmedien}, address = {M{\"u}nchen}, issn = {0933-8667}, pages = {26 -- 31}, year = {2018}, language = {de} } @article{RoehlenPilasDahmenetal.2018, author = {R{\"o}hlen, Desiree and Pilas, Johanna and Dahmen, Markus and Keusgen, Michael and Selmer, Thorsten and Sch{\"o}ning, Michael Josef}, title = {Toward a Hybrid Biosensor System for Analysis of Organic and Volatile Fatty Acids in Fermentation Processes}, series = {Frontiers in Chemistry}, journal = {Frontiers in Chemistry}, number = {6}, publisher = {Frontiers}, address = {Lausanne}, doi = {10.3389/fchem.2018.00284}, pages = {Artikel 284}, year = {2018}, abstract = {Monitoring of organic acids (OA) and volatile fatty acids (VFA) is crucial for the control of anaerobic digestion. In case of unstable process conditions, an accumulation of these intermediates occurs. In the present work, two different enzyme-based biosensor arrays are combined and presented for facile electrochemical determination of several process-relevant analytes. Each biosensor utilizes a platinum sensor chip (14 × 14 mm²) with five individual working electrodes. The OA biosensor enables simultaneous measurement of ethanol, formate, d- and l-lactate, based on a bi-enzymatic detection principle. The second VFA biosensor provides an amperometric platform for quantification of acetate and propionate, mediated by oxidation of hydrogen peroxide. The cross-sensitivity of both biosensors toward potential interferents, typically present in fermentation samples, was investigated. The potential for practical application in complex media was successfully demonstrated in spiked sludge samples collected from three different biogas plants. Thereby, the results obtained by both of the biosensors were in good agreement to the applied reference measurements by photometry and gas chromatography, respectively. The proposed hybrid biosensor system was also used for long-term monitoring of a lab-scale biogas reactor (0.01 m³) for a period of 2 months. In combination with typically monitored parameters, such as gas quality, pH and FOS/TAC (volatile organic acids/total anorganic carbonate), the amperometric measurements of OA and VFA concentration could enhance the understanding of ongoing fermentation processes.}, language = {en} } @article{JildehOberlaenderKirchneretal.2018, author = {Jildeh, Zaid B. and Oberl{\"a}nder, Jan and Kirchner, Patrick and Wagner, Patrick H. and Sch{\"o}ning, Michael Josef}, title = {Thermocatalytic Behavior of Manganese (IV) Oxide as Nanoporous Material on the Dissociation of a Gas Mixture Containing Hydrogen Peroxide}, series = {Nanomaterials}, volume = {8}, journal = {Nanomaterials}, number = {4}, publisher = {MDPI}, address = {Basel}, issn = {2079-4991}, doi = {10.3390/nano8040262}, pages = {Artikel 262}, year = {2018}, abstract = {In this article, we present an overview on the thermocatalytic reaction of hydrogen peroxide (H₂O₂) gas on a manganese (IV) oxide (MnO₂) catalytic structure. The principle of operation and manufacturing techniques are introduced for a calorimetric H₂O₂ gas sensor based on porous MnO₂. Results from surface analyses by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) of the catalytic material provide indication of the H₂O₂ dissociation reaction schemes. The correlation between theory and the experiments is documented in numerical models of the catalytic reaction. The aim of the numerical models is to provide further information on the reaction kinetics and performance enhancement of the porous MnO₂ catalyst.}, language = {en} } @article{WilsonDickieSchreiteretal.2018, author = {Wilson, C. E. and Dickie, A. P. and Schreiter, K. and Wehr, R. and Wilson, E. M. and Bial, J. and Scheer, Nico and Wilson, I. D. and Riley, R. J.}, title = {The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice}, series = {Archives of Toxicology}, volume = {92}, journal = {Archives of Toxicology}, number = {6}, publisher = {Springer}, issn = {1432-0738}, doi = {10.1007/s00204-018-2212-1}, pages = {1953 -- 1967}, year = {2018}, abstract = {The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.}, language = {en} }