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Visual function restoration with a highly sensitive and fast Channelrhodopsin in blind mice

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1389-1391页

作者： Fei Chen Xiaodong Duan Yao Yu Shang Yang Yuanyuan Chen Christine Egee georg nagel Kang Zhang Shiqiang gao Yin Shen Eye Center Wuhan University Renmin HospitalWuhanChina Department of Neurophysiology Institute of PhysiologyBiocenterUniversity of WuerzburgWuerzburgGermany Institute for Synaptic Physiology University Medical Center Hamburg EppendorfHamburgGermany Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and Technology and University HospitalMacaoChina Frontier Science Center for Immunology and Metabolism and Medical Research Institute at School of MedicineWuhan UniversityWuhanChina

Inherited and age-related retinal degenerative diseases cause progressive loss of photoreceptors,ultimately leading to *** is a promising strategy for restoring visual function through photosensitive proteins’ectopic expression in surviving retinal neurons.1 Very recently,the optogenetic method with a red-shifted Channelrhodopsin was clinically applied for partial recovery of visual function in a blind patient.2 However,major obstacles to achieving optimal optogenetic vision restoration are either the low light sensitivity or the slow kinetics of existing rhodopsin-based optogenetic tools,which can be improved by molecular engineering to enhance the efficacy of fast Channelrhodopsins(ChRs).

关键词： Visual visual function

The Effect of Delivery Method on the Pharmacokinetic Properties of Meloxicam in Pre-Weaned Dairy Calves with Diarrhea

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Open Journal of Veterinary Medicine 2020年第3期10卷 27-38页

作者： Daniel Shock Steven Roche Denis nagel Merle Olson ACER Consulting Guelph Canada Alberta Veterinary Labs/Solvet Inc. Calgary Canada

The non-steroidal anti-inflammatory drug meloxicam is commonly used as adjunct therapy for neonatal calf diarrhea to control pain and inflammation. The objective of this study was to compare the pharmacokinetics of meloxicam in diarrheic pre-ruminant dairy calves dosed either orally or subcutaneously. Twelve pre-ruminant male dairy calves with mild to moderate diarrhea were randomly assigned to receive one of four treatments (three per group): subcutaneous meloxicam (SM, 0.5 mg/kg body weight);an oral bolus meloxicam suspension (OM, 1 mg/kg body weight);an oral meloxicam suspension added to a feeding of oral electrolytes (EM, 1 mg/kg body weight);and an oral meloxicam suspension added to a feeding of milk replacer (MM, 1 mg/kg body weight). The predicted pharmacokinetic parameters for OM, MM, EM, and SM groups were: half-life (56.8 ± 21.7 vs. 136.0 ± 26.6 vs. 85.2 ± 21.7 vs. 36.3 ± 21.7 h), Cmax (4.3 ± 0.4 vs. 3.7 ± 0.4 vs. 3.9 ± 0.4 vs. 2.1 ± 0.4 μg/mL), Tmax (13.3 ± 4.0 vs. 10.7 ± 4.0 vs. 13.3 ± 4.0 vs. 2.7 ± 4.0 h), and AUC0-∞ (383.4 ± 126.8 vs. 877.8 ± 155.3 vs. 457.1 ± 126.8 vs. 126.4 ± 126.8 h * μg/mL). Oral meloxicam, especially MM, had extended elimination phases relative to SM. All meloxicam therapies provided effective therapeutic levels but all oral therapies (1 mg/kg) provided longer durations of activity than injectable meloxicam (0.5 mg/kg).

关键词： Meloxicam Dairy Calves Pharmacokinetics Diarrhea Anti-Inflammatory

Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model

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World Journal of Hepatology 2016年第8期8卷 401-410页

作者： Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L gerbes Simon Hohenester gerald U Denk Department of Medicine Ⅱ Liver Center Munich University of Munich Institute of Pathology University of Munich Department of Medicine Ⅰ Krankenhaus Barmherzige Brüder Research Unit for Experimental and Molecular Hepatology Division of Gastroenterology and Hepatology Department of Internal Medicine Hans Popper Laboratory of Molecular Hepatology Division of Gastroenterology and Hepatology Department of Internal Medicine Ⅲ Medical University of Vienna Transplant Center Munich of the University of Munich

AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse ***: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P genic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P gnificantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P gnificantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-te

关键词： Cholestasis Primary sclerosing cholangitis The ATP-binding cassette transporter b4 Liver fibrosis Interleukin-1

MRI双向反转恢复序列在心肌瘢痕钆增强成像中延迟血液信号减少的应用

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国际医学放射学杂志 2012年第5期 479-480页

作者： S.A.Peel g.Morton A.Chiribiri A.Schuster E.nagel R.M.Botnar 倪玲 Division of Imaging Sciences and Biomedical Engineering King's College LondonRayne Institute4th Floor Lambeth WingSt Thomas' HospitalWestminster Bridge RdSE1 7EH LondonEngland

摘要目的研究3.0TMRI上的标准反转恢复(IR)序列相比,双向IR预脉冲在心肌瘢痕钆延时增强检查中是否提高瘢痕-血液对比和专家的诊断信心及一致性。方法这项研究得到当地伦理委员会的批准,所有病人均签署了书面知情同意书。12例有心肌瘢痕... 详细信息

摘要目的研究3.0TMRI上的标准反转恢复(IR)序列相比,双向IR预脉冲在心肌瘢痕钆延时增强检查中是否提高瘢痕-血液对比和专家的诊断信心及一致性。方法这项研究得到当地伦理委员会的批准,所有病人均签署了书面知情同意书。12例有心肌瘢痕的男性病人[平均年龄(63±8)岁]在注射0.2mmol/kg钆布醇10、20和30min后分别使用标准的和双向IR序列进行MR成像。

关键词：反转恢复瘢痕 MRI 序列血液解剖学心肌

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政策研究百科全书

采用T1 mapping和T2 mapping早期识别系统性结节病累及心脏

1990年

作者： S.S.·那格尔(S.S. nagel)

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国际医学放射学杂志 2017年第6期 720-721页

作者： V.O.Puntmann A.Isted R.Hinojar L.Foote g.Carr-White E.nagel 刘莹 Department of Cardiology Guy ’s and St Thomas’ NHS Trust

摘要目的研究T1mapping和T2mapping的组织表征定量是否有助于提高识别系统性结节病病人累及心肌。材料与方法 53例经活检证实为全身结节病病人(21例男性;平

关键词：系统性结节病 T2 mapping T1 mapping

PET/MR一体机采用TOF BSREM重建技术以降低盆腔成像的68ga-PSMA-11使用剂量

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国际医学放射学杂志 2020年第4期 500-500页

作者： H.Svirydenka U.J.Muehlematter H.W.nagel g.Delso D.A.Ferraro K.Kudura 江伟 Department of Nuclear Medicine University Hospital Zurich

目的在PET/MR一体机中,PET采集时间的延长,既匹配了MRI扫描方案,又可籍此降低示踪剂的注射剂量以减少辐射。此外,应用新的、可商用的基于飞行时间

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3TMR扩散加权成像和MR引导下的活检术对于前列腺炎和前列腺癌的鉴别诊断

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国际医学放射学杂志 2013年第3期 277-277页

作者： K.N.A.nagel M.g.Schouten T.Hambrock g.J.S Litjens C.M.A.Hoeks B.ten Haken 冯锐 Department of Radiology Radboud University Nijmegen Medical Centre

目的以MR引导下的活检标本作为参考标准,判定MR表观扩散系数(ADC)对于前列腺炎及前列腺癌的鉴别诊断价值。材料与方法研究免除了机构审查委员会的批准和知情同意。对于连续130例病人在3T多参数MR影像中的肿瘤可疑区域(CSR)进行MR引导下... 详细信息

目的以MR引导下的活检标本作为参考标准,判定MR表观扩散系数(ADC)对于前列腺炎及前列腺癌的鉴别诊断价值。材料与方法研究免除了机构审查委员会的批准和知情同意。对于连续130例病人在3T多参数MR影像中的肿瘤可疑区域(CSR)进行MR引导下的活检。本项回顾性研究中,88例病人符合入组标准。在活检过程中,采用横断位扩散加权序列扫描并产生ADC图(重复时间/回波时间2000ms/67ms;层厚4mm;平面分辨率1.8mm×1.8mm;b值0、100、500和800s/mm2)。随后获取一张确认穿刺针存留于病灶内的影像并且投射到ADC图中。将活检部位对应的ADC值与活检标本的病理结果相对比。采用线性混合模型回归分析方法对不同病理组间的ADC值的差异进行检验。结果这项研究包括116个活检标本。正常前列腺组织、前列腺炎、低度恶性前列腺癌(gleason分级评分2或3)和高度恶性前列腺癌(gleason分级评分4或5)4组的ADC值的中位数分别为(1.22±0.21)×10-3mm2/s,(1.08±0.18)×10-3mm2/s,(0.88±0.15)×10-3mm2/s和(0.88±0.13)×10-3mm2/s。虽然前列腺炎活检标本的ADC中位数明显高于低度恶性和高度恶性前列腺癌(P<0.001),但不同组织类型之间仍有相当大的重叠。结论尽管ADC图结果的重叠性使得其在临床的应用中有局限性,但扩散加权成像作为一项无创性技术,仍可以显示发生在外周带和中央腺的前列腺炎和前列腺癌之间的信号差异。

关键词：前列腺癌活检标本 ADC 前列腺炎 MR 鉴别诊断加权成像

3.0 T磁场强度下水负荷前后人体肾23Na-MR成像的定量和定性研究

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国际医学放射学杂志 2011年第6期 584-584页

作者： S.Haneder S.Konstandin J.N.Morelli A.M.nagel F.g.Zoellner L.R.Schad 王焕军 Institute of Clinical Radiology and Nuclear Medicine University Medical Centre MannheimMedical Faculty MannheimHeidelberg UniversityTheodor-Kutzer-Ufer 1-368167 MannheimGermany

目的采用3TMRI定性和定量评估水负荷前后人肾皮髓质对23Na的浓聚情况。材料与方法 14名健康志愿者(24～34岁,平均年龄28岁)被纳入此项研究。本研究经学术审查委员会批准,研究时间自2009年7月—12月。23Na-MR成像采用可依密度进行放射状... 详细信息

目的采用3TMRI定性和定量评估水负荷前后人肾皮髓质对23Na的浓聚情况。材料与方法 14名健康志愿者(24～34岁,平均年龄28岁)被纳入此项研究。本研究经学术审查委员会批准,研究时间自2009年7月—12月。23Na-MR成像采用可依密度进行放射状调整的3D梯度回

关键词： MR 皮髓质 Na-MR