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Evaluation of imipenem toxicity in cynomolgus macaques including assessment of biomarkers of renal damage

中国药理学与毒理学杂志 2013年第3期 492-493页

作者： YU Hong Sonya GALES ZHENG Wei-jun QIN Qiu-ping Dale THURMAN HU Li-ping QIAO Jun-wen REN Jin CHEN Ya-fei Russell BIALECKI lew kinter Nigel BARRASS Centre for Drug Safety Evaluation and Research Shanghai Institute of Materia Medica AstraZeneca R&D Alderley Park MacclesfieldUK Global Safety Assessment AstraZeneca R&D BostonMAUSA

OBJECTIVE To assess the nephrotoxicity of imipenem and to correlate the pathogenesis of lesions in the kidney with changes in urinary biomarkers of kidney *** Study #1,11 monkeys(2-3 /sex /group) were given vehicle or imipenem(180 mg·kg-1,iv infusion once daily for 7 d) and urine was collected on days xxxxx for biomarker *** Study #2,24 monkeys(3 /sex /group) were given of vehicle or imipenem(45,90 or 180 mg·kg-1,iv infusion once daily for 7 d).The following endpoints were assessed in both studies: clinical observations,body weight,food consumption,haematology,coagulation,blood chemistry,urine analysis,imipenem concentration /toxicokinetics (TK) and gross and microscopic *** Study #1: Imipenem causes minor body weight loss,increased urea and creatinine,and decreased phosphate in *** total protein and bilirubin were observed in the *** effects were progressive and most pronounced at days 7 and *** and relative kidney weights were increased in both *** histopathological findings were present in kidneys of the dosed monkeys,consisting of minimal to moderate tubular necrosis /degeneration /*** biomarkers(α-1 and β-2 microglobulin,clusterin,Tamm-Horsfall protein and vascular endothelial growth factor) increased progressively and significantly from day 2 onward and preceded notable changes in urinalysis or plasma chemistry on day 7 or 8,*** #2: There were similar findings to Study #1 in the 180 mg·kg-1 imipenem treatment *** total bilirubin and decreased of phosphate in plasma and an increase of urinary urobilinogen /ketones were observed in a dose related *** to imipenem 〔Cmax and AUC(0-3 h) 〕increased in proportion from 45-90 mg·kg-1 but more than in proportion from 90-180 mg·*** The no observed adverse effect level(NOAEL) for the imipenem induced kidney injury was identified as 90 mg·*** increases of five urinary biomark

关键词： imipenem toxicity biomarkers renal damage

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Evaluation of cisplatin-induced toxicity in cynomolgus macaques including assessment of potential biomarkers of renal toxicity

Evaluation of cisplatin-induced toxicity in cynomolgus macaq...

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2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

OBJECTIVE Cisplatin-induced nephrotoxicity has been characterized previously in animals and humans. Two studies were conducted in cynomolgus macaques to assess the nephrotoxicity of cisplatin and to correlate the pathogenesis of lesions in the kidneys with expression of a panel of potential urinary biomarkers of kidney *** In study #1,6 monkeys(1/sex/group) were given a single *** of cisplatin(1.25,2.5 and 5 mg·kg) and were terminated for necropsy on day 7 *** Study #2,36 monkeys(3/sex/group) were given a single iv infusion of vehicle or cisplatin(2.5 mg·kg) and then they were terminated for necropsy on days 2,5,10 or 21,respectively, post - *** following endpoints were assessed in both studies:clinical observations,body weight,food consumption, haematology,coagulation,blood chemistry,urine analysis,cisplatin concentration/toxicokinetics(TK) and gross and microscopic *** of biomarkers for drug-induced kidney injury(DIKI) was confined to Study #*** Study #1:A single intravenous administration of cisplatin induced occasional vomiting,decreased motor activity, reduced food consumption and minor body weight loss at the highest dose(5 mg·kg).Urea and creatinine were markedly increased,plasma electrolytes showed dose-related alterations and blood and proteins were found in the urine. The high dose animals had reduced urine *** weights were increased following 2.5 and 5 mg·kg and there were progressive renal histopathological *** to cisplatin[C and AUC(04))]increased slightly more than in proportion to the dose of cisplatin across the dose *** #2:One male dosed at 2.5 mg·kg cisplatin was prematurely terminated on day *** other animals survived to their scheduled *** evaluation demonstrated that kidney lesions progressed with *** chemistry results indicated that 7 out of 24 animals treated with cisplatin had moderately to markedly increased urea and

关键词： cisplatin renal toxicity biomarkers

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Evaluation of cisplatin-induced toxicity in cynomolgus macaques including assessment of potential biomarkers of renal toxicity

Evaluation of cisplatin-induced toxicity in cynomolgus macaq...

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作者： YU Hong Sonya GALES ZHENG Wei-jun QIN Qiu-ping Dale THURMAN QIAO Jun-wen REN Jin CHEN Ya-fei Russell BIALECKI lew kinter Nigel BARRASS Global Safety Assessment Centre for Drug Safety Evaduation and Research Shanghai Institute of Materia Medica AstraZeneca R&D Alderley Park

OBJECTIVE Cisplatin-induced nephrotoxicity has been characterized previously in animals and humans. Two studies were conducted in cynomolgus macaques to assess the nephrotoxicity of cisplatin and to correlate the pathogenesis of lesions in the kidneys with expression of a panel of potential urinary biomarkers of kidney *** In study #1,6 monkeys(1/sex/group) were given a single *** of cisplatin(1.25,2.5 and 5 mg·kg~(-1)) and were terminated for necropsy on day 7 *** Study #2,36 monkeys(3/sex/group) were given a single iv infusion of vehicle or cisplatin(2.5 mg·kg~(-1)) and then they were terminated for necropsy on days 2,5,10 or 21,respectively, *** following endpoints were assessed in both studies:clinical observations,body weight,food consumption, haematology,coagulation,blood chemistry,urine analysis,cisplatin concentration/toxicokinetics(TK) and gross and microscopic *** of biomarkers for drug-induced kidney injury(DIKI) was confined to Study #*** Study #1:A single intravenous administration of cisplatin induced occasional vomiting,decreased motor activity, reduced food consumption and minor body weight loss at the highest dose(5 mg·kg~(-1)).Urea and creatinine were markedly increased,plasma electrolytes showed dose-related alterations and blood and proteins were found in the urine. The high dose animals had reduced urine *** weights were increased following 2.5 and 5 mg·kg~(-1) and there were progressive renal histopathological *** to cisplatin〔C_(max) and AUC_((0-24))〕increased slightly more than in proportion to the dose of cisplatin across the dose *** #2:One male dosed at 2.5 mg·kg~(-1) cisplatin was prematurely terminated on day *** other animals survived to their scheduled *** evaluation demonstrated that kidney lesions progressed with *** chemistry results indicated that 7 out of 24 animals treated with cisplatin had moderatel

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Evaluation of cisplatin-induced toxicity in cynomolgus macaques including assessment of potential biomarkers of renal toxicity

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中国药理学与毒理学杂志 2013年第3期 466-466页

作者： YU Hong Sonya GALES ZHENG Wei-jun QIN Qiu-ping Dale THURMAN QIAO Jun-wen REN Jin CHEN Ya-fei Russell BIALECKI lew kinter Nigel BARRASS Centre for Drug Safety Evaduation and Research Shanghai Institute of Materia Medica AstraZeneca R&D Alderley Park MacclesfieldUK Global Safety Assessment AstraZeneca R&D BostonMAUSA

OBJECTIVE Cisplatin-induced nephrotoxicity has been characterized previously in animals and *** studies were conducted in cynomolgus macaques to assess the nephrotoxicity of cisplatin and to correlate the pathogenesis of lesions in the kidneys with expression of a panel of potential urinary biomarkers of kidney *** In study #1,6 monkeys(1 /sex /group) were given a single *** of cisplatin(1.25,2.5 and 5 mg·kg-1) and were terminated for necropsy on day 7 *** Study #2,36 monkeys(3 /sex /group) were given a single iv infusion of vehicle or cisplatin(2.5 mg·kg-1) and then they were terminated for necropsy on days 2,5,10 or 21,respectively,*** following endpoints were assessed in both studies: clinical observations,body weight,food consumption,haematology,coagulation,blood chemistry,urine analysis,cisplatin concentration /toxicokinetics(TK) and gross and microscopic *** of biomarkers for drug-induced kidney injury(DIKI) was confined to Study #*** Study #1: A single intravenous administration of cisplatin induced occasional vomiting,decreased motor activity,reduced food consumption and minor body weight loss at the highest dose(5 mg·kg-1).Urea and creatinine were markedly increased,plasma electrolytes showed dose-related alterations and blood and proteins were found in the *** high dose animals had reduced urine *** weights were increased following 2.5 and 5 mg·kg-1 and there were progressive renal histopathological *** to cisplatin〔Cmax and AUC(0-24) 〕increased slightly more than in proportion to the dose of cisplatin across the dose *** #2: One male dosed at 2.5 mg·kg-1 cisplatin was prematurely terminated on day *** other animals survived to their scheduled *** evaluation demonstrated that kidney lesions progressed with *** chemistry results indicated that 7 out of 24 animals treated with cisplatin had moderately to markedly inc

关键词： cisplatin renal toxicity biomarkers

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Evaluation of imipenem toxicity in cynomolgus macaques including assessment of biomarkers of renal damage

Evaluation of imipenem toxicity in cynomolgus macaques inclu...

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作者： YU Hong Sonya GALES ZHENG Wei-jun QIN Qiu-ping Dale THURMAN HU Li-ping QIAO Jun-wen REN Jin CHEN Ya-fei Russell BIALECKI lew kinter Nigel BARRASS Centre for Drug Safety Evaluation and Research Shanghai Institute of Materia Medica Global Safety Assessment AstraZeneca R&D Alderley Park

OBJECTIVE To assess the nephrotoxicity of imipenem and to correlate the pathogenesis of lesions in the kidney with changes in urinary biomarkers of kidney *** Study #1,11 monkeys(2 -3/sex/group) were given vehicle or imipenem(180 mg·kg~(-1),iv infusion once daily for 7 d) and urine was collected on days xxxxx for biomarker *** Study #2,24 monkeys(3/sex/group) were given of vehicle or imipenem(45,90 or 180 mg·kg~(-1),iv infusion once daily for 7 d).The following endpoints were assessed in both studies:clinical observations,body weight, food consumption,haematology,coagulation,blood chemistry,urine analysis,imipenem concentration/toxicokinetics (TK) and gross and microscopic *** Study #1:Imipenem causes minor body weight loss,increased urea and creatinine,and decreased phosphate in *** total protein and bilirubin were observed in the urine. These effects were progressive and most pronounced at days 7 and *** and relative kidney weights were increased in both *** histopathological findings were present in kidneys of the dosed monkeys,consisting of minimal to moderate tubular necrosis/degeneration/*** biomarkers(α-1 andβ-2 microglobulin,clusterin, Tamm-Horsfall protein and vascular endothelial growth factor) increased progressively and significantly from day 2 onward and preceded notable changes in urinalysis or plasma chemistry on day 7 or 8,*** #2:There were similar findings to Study #1 in the 180 mg·kg~(-1) imipenem treatment *** total bilirubin and decreased of phosphate in plasma and an increase of urinary urobilinogen/ketones were observed in a dose related *** to imipenem〔C_(max) and AUC_(0-3h)〕increased in proportion from 45 -90 mg·kg~(-1) but more than in proportion from 90-180 mg·kg~(-1). CONCLUSION The no observed adverse effect level(NOAEL) for the imipenem induced kidney injury was identified as 90 mg·kg~(-1).Early increases of five ur

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Evaluation of imipenem toxicity in cynomolgus macaques including assessment of biomarkers of renal damage

Evaluation of imipenem toxicity in cynomolgus macaques inclu...

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2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

OBJECTIVE To assess the nephrotoxicity of imipenem and to correlate the pathogenesis of lesions in the kidney with changes in urinary biomarkers of kidney *** Study #1,11 monkeys(2 -3/sex/group) were given vehicle or imipenem(180 mg·kg,iv infusion once daily for 7 d) and urine was collected on days xxxxx for biomarker *** Study #2,24 monkeys(3/sex/group) were given of vehicle or imipenem(45,90 or 180 mg·kg,iv infusion once daily for 7 d).The following endpoints were assessed in both studies:clinical observations,body weight, food consumption,haematology,coagulation,blood chemistry,urine analysis,imipenem concentration/toxicokinetics (TK) and gross and microscopic *** Study #1:Imipenem causes minor body weight loss,increased urea and creatinine,and decreased phosphate in *** total protein and bilirubin were observed in the urine. These effects were progressive and most pronounced at days 7 and *** and relative kidney weights were increased in both *** histopathological findings were present in kidneys of the dosed monkeys,consisting of minimal to moderate tubular necrosis/degeneration/*** biomarkers(α-1 andβ-2 microglobulin,clusterin, Tamm-Horsfall protein and vascular endothelial growth factor) increased progressively and significantly from day 2 onward and preceded notable changes in urinalysis or plasma chemistry on day 7 or 8,*** #2:There were similar findings to Study #1 in the 180 mg·kg imipenem treatment *** total bilirubin and decreased of phosphate in plasma and an increase of urinary urobilinogen/ketones were observed in a dose related *** to imipenem [C and AUC(0-3h))) increased in proportion from 45 -90 mg-kg but more than in proportion from 90-180 mg·kg. CONCLUSION The no observed adverse effect level(NOAEL) for the imipenem induced kidney injury was identified as 90 mg·*** increases of five urinary biomarkers of kidney toxicit

关键词： imipenem toxicity biomarkers renal damage

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Spin-based magnetic random-access memory for high-performance computing

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National Science Review 2024年第3期11卷 20-23页

作者： Kaiming Cai Tianli Jin Wen Siang lew School of Physics Huazhong University of Science and Technology Interuniversity Microelectronics Centre(IMEC) School of Physical and Mathematical Sciences Nanyang Technological University

Memory serves as a critical component in today's electronic systems for data storage and processing. In traditional computer architectures, the logic and memory units are physically separated, due to the performance gap in operational speed and capacity among memories, resulting in the fundamental limitation of the von Neumann computers.

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Synthesis and electrochemical properties of dual doped spinels LiNi_xAl_yMn_(2-x-y)O_4 via facile novel chelated sol–gel method as possible cathode material for lithium rechargeable batteries

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Journal of Energy Chemistry 2017年第1期26卷 101-114页

作者： R.Thirunakaran Gil Hwan lew Won-Sub Yoon CSIR-Central Electrochemical Research Institute Sungkyunkwan University Department of Energy Science

LiMnOand LiNiAlyMnO（x= 0.50;y = 0.05-0.50） powders have been synthesized via facile solgel method using Behenic acid as active cheiating *** synthesized samples are subjected to physical characterizations such as thermo gravimetric analysis（TG/DTA）,X-ray diffraction（XRD）,Fourier transform infrared spectroscopy（FT-IR）,field-emission scanning electron microscopy（FESEM）,transmission electron microscopy（TEM） and electrochemical studies viz.,galvanostatic cycling properties,electrochemical impedance spectroscopy（EIS） and differential capacity curves（dQ/dE）.Finger print XRD patterns of LiMnOand LiNiAlMnOfortify the high degree of crystallinity with better phase *** images of the undoped pristine spinel illustrate uniform spherical grains surface morphology with an average particle size of 0.5 μm while Ni doped particles depict the spherical grains growth（50nm） with ice-cube surface *** images of the spinel LiMnOshows the uniform spherical morphology with particle size of（100 nm） while low level of Al-doping spinel（LiNio.5Alo.05Mn1.45O4） displaying cloudy particles with agglomerated particles of（50nm）.The LiMnOsamples calcined at 850℃ deliver the discharge capacity of 130 mAh/g in the first cycle corresponds to 94%coiumbic efficiency with capacity fade of 1.5 mAh/g/cycle over the investigated 10 *** all four dopant compositions investigated,LiNiAlMnOdelivers the maximum discharge capacity of 126 mAh/g during the first cycle and shows the stable cycling performance with low capacity fade of 1 mAh/g/cycle（capacity retention of 92%） over the investigated 10 *** impedance studies of spinel LiMnOand LiNiAlMnOdepict the high and low real polarization of 1562 and 1100 Ω.

关键词： Multi-doping Sol–gel method Behenic acid Differential capacity Spinel cathode

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Designing architected materials for mechanical compression via simulation, deep learning, and experimentation

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npj Computational Materials 2023年第1期9卷 1534-1542页

作者： Andrew J.lew Kai Jin Markus J.Buehler Laboratory for Atomistic and Molecular Mechanics(LAMM) Massachusetts Institute of Technology77 Massachusetts Ave.CambridgeMA 02139USA Department of Chemistry Massachusetts Institute of Technology77 Massachusetts Ave.CambridgeMA 02139USA Center for Computational Science and Engineering Schwarzman College of ComputingMassachusetts Institute of Technology77 Massachusetts Ave.CambridgeMA 02139USA

Architected materials can achieve enhanced properties compared to their plain *** architecting serves as a powerful design lever to achieve targeted behavior without changing the base ***,the connection between architected structure and resultant properties remains an open field of great interest to many fields,from aerospace to civil to automotive ***,we focus on properties related to mechanical compression,and design hierarchical honeycomb structures to meet specific values of stiffness and compressive *** do so,we employ a combination of techniques in a singular workflow,starting with molecular dynamics simulation of the forward design problem,augmenting with data-driven artificial intelligence models to address the inverse design problem,and verifying the behavior of de novo structures with experimentation of additively manufactured *** thereby demonstrate an approach for architected design that is generalizable to multiple material properties and agnostic to the identity of the base material.

关键词： thereby additive starting

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A case of branch retinal artery obstruction complicated after anterior ischemic optic neuropathy

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International Journal of Ophthalmology(English edition) 2011年第4期4卷 447-448页

作者： Ungsoo Samuel Kim Hyoung-Seok Kim Young Ju lew Department of Ophthalmology Kim's Eye Hospital Konyang University College of Medicine

AIM: To report a case of branch retinal artery obstruction (BRAO) complicated after anterior ischemic optic neuropathy (AION). METHODS: A 42 year-old woman who complained of visual disturbance was performed ophthalmological examinations such as fundus photography, fluorescent angiography (FAG) and visual field test. RESULTS: At first visit, disc swelling was noted and arterial circulation was intact, however, 1 week after onset, the inferior branch retinal artery began to shrink and the flame hemorrhage intensified. Sixteen months later, the optic disc evidenced an atrophic change; additionally, a ghost vessel in the inferior branch retinal artery was found. CONCLUSION: We report a case of complications of BRAO arising after AION which caused the mechanical compression on the arterial circulation.

关键词： anterior ischemic optic neuropathy branch retinal artery obstruction complication fluorescent angiography

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