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The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling Alistair james Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran Charlotte Gray-Hammerton Claudia Orbegozo Rubio Edgars Suna jordan Mathias j.rgen brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher joseph Schofield Timothy Walsh Department of Biology&Ineos Oxford Institute for Antimicrobial Research University of OxfordOxford OX13REUK Chemistry Research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian Institute of Organic Synthesis Riga LV-1006Latvia Department of Medical Microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis Research Center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with InC58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： Carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance

Local immunotherapy with interleuk in-2 delivered from biodegradable p olymer microspheres combined with interstitial chemotherapy:a novel treatme nt for experimental malignant glioma

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癌症 2003年第7期22卷 752-752页

作者： Rhines LD DiMeco F Lawson HC Tyler BM Hanes j Olivi A brem H

OBjECTIVE:Local delivery of carmustine(BCNU)from biodegradable polymers prolon gs survival against experimental brain ***,paracrine administration of inte rleukin-2(IL-2)has been shown to elicit a potent antitumor immune response and to improve survival in animal brain tumor *** r eport the use of a novel polymeric mic rosphere delivery vehicle to release *** demonstr ate both in vitro release of cytokine from the microspheres and histological evidence of the inflammatory response elicited by I L-2released from the microspheres i n the rat *** microspheres a re used to deliver IL-2,and biodegradable polymer wafers are used to deliver BCNU,directly at the site of an intracranially implanted glioma in the *** two agents administered locally show a s ynergistic ***:Fischer 344rats challenged intracranially with 9L gliosarcoma received an intracranial implant of either empty microspheres or microspheres containing IL-2(IL-2MS ).Five days later,animals in each group were randomized to receiv e polymer implants loaded with 0,3.8,or 10%BCNU at the tumor ***:Animals that received the combination of IL-2MS a nd 3.8%BCNU polymer(median survival,28.5d )or IL-2MS and 10%BCNU polymer(median survival,45.5d )showed significantly improved surv ival compared with animals that rece ived monotherapy with IL-2microsph eres(median survival,24d ),3.8%BCNU polymer(median survival,24d ),or 10%BCNU polymer(median survival,32.5d ).Control animals had a median survival of *** combination of either 3.8or 10%BCNU polymer with IL-2MS resulted in 7and 25%long-term survivors,***:By showing synergy of IL-2and BCNU in an animal glioma model and using a reproducible synthetic delivery sy stem for each agent (i.e.,one that did not rely on genetic ally engineered cells or viruses),we hope that the combination of local immunotherapy and chemotherapy can take an important step closer to clinical applic ation in patients with

关键词：实验性神经胶质瘤 IL-2 腔内化疗

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基因转移在动物育种中的研究与应用

内蒙古畜牧科学 1992年第1期13卷 36-40,F003页

作者： Gottfried brem 李善如

目前,人工授精和胚胎移植已被成功地、广泛地应用于动物育种中,同时人们还在胚胎移植领域开展了胎胚显微手术、胚胎体外生产以及近几年发展极为迅速的基因转移技术。与其他育种方法和育种技术不同,基因转移首次通过单个基因的转移进行... 详细信息

目前,人工授精和胚胎移植已被成功地、广泛地应用于动物育种中,同时人们还在胚胎移植领域开展了胎胚显微手术、胚胎体外生产以及近几年发展极为迅速的基因转移技术。与其他育种方法和育种技术不同,基因转移首次通过单个基因的转移进行育种。基因转移就是把在体外重组的基因导入到动物基因组型内。所转移的基因是在体外由结构基因和调节物(操纵子)重组而成的转录单位。已被整合到动物基因组型内的基因被称为转基因,获得这种转基因的动物被称为转基因动物。如果这种转基因被后代所继承,那么就可发展成为转基因系。

关键词：基因转移动物育种

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转基因家畜

国外畜牧学（草食家畜） 1992年第4期 1-6页

作者： G.brem H-G.Wagner 张富春张居农马纪

1980年,首次报道了用DNA显微注射法成功地获得转基因鼠的实验(Gordon等,1980),从此建立了单一离体基因转移的方法。利用70年代发展起来的分子生物学技术,对有利育种的基因可以进行分离、测序以及同调控结构重组,并在体内和体外检测其表... 详细信息

1980年,首次报道了用DNA显微注射法成功地获得转基因鼠的实验(Gordon等,1980),从此建立了单一离体基因转移的方法。利用70年代发展起来的分子生物学技术,对有利育种的基因可以进行分离、测序以及同调控结构重组,并在体内和体外检测其表达能力。虽然这一基础方法在动物育种领域刚刚起步,但未来前景广阔。本文综述了已建立的基因转移技术和家畜基因转移现状。基因转移技术基因转移是指将体外重组基因结构导入动物体的技术。

关键词：家畜基因转移

心脏MRI评估优秀铁人三项运动员心脏房室功能和结构适应能力

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国际医学放射学杂志 2010年第6期 571-572页

作者： M.Scharf M.H.brem M.Wilhelm U.j.Schoepf M.Uder M.M.Lell 何珍 Departments of Radiology University of Erlangen NurembergMaximiliansplatz 191054 ErlangenGermany

目的使用MRI评估运动员心脏形态和机能的适应性,并且与休养对照组进行比较。材料与方法本研究经机构审查委员会同意,所有参与者均签署知情同意书。26名男

关键词： MRI 心脏形态右室左室铁人三项心脏运动员体育工作者功能

Local immunotherapy with interleukin - 2 delivered from biodegradable polymer microspheres combined with interstitial chemotherapy: a novel treatment for experimental malignant glioma.

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中国神经肿瘤杂志 2003年第2期1卷 81-81页

作者： Rhines LD DiMeco F Lawson HC Tyler BM Hanes j Olivi A brem H Department of Neurosurgery University of Texas M. D.Anderson Cancer CenterHoustonTexas.

OBjECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain ***,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent antitumor immune response and to improve survival in animal brain tumor *** report the use of anovel polymeric microsphere delivery vehicle to release *** demonstrate both in vitro release of cytokinefrom the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from themicrospheres in the rat *** microspheres are used to deliver IL-2,and biodegradable polymer wafers

关键词： BCNU Local immunotherapy with interleukin from delivered from biodegradable polymer microspheres combined with interstitial chemotherapy a novel treatment for experimental malignant glioma for with

移植耐受诱导细胞在肾移植受者免疫干预中的临床应用

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中华移植杂志（电子版） 2009年第1期3卷 59-59页

作者：何强 Hutchinson jA Riquelme P brem-Exner BG

德国研究者在前期研究基础上通过体外培养和免疫干预一类巨噬细胞获取移植耐受诱导细胞(transplant acceptance-inducing cells,TAICs)并在前期动物实验中证实应用TAICs可以在一定程度上特异性减轻排斥反应,使移植受者可以安全地减少传... 详细信息

德国研究者在前期研究基础上通过体外培养和免疫干预一类巨噬细胞获取移植耐受诱导细胞(transplant acceptance-inducing cells,TAICs)并在前期动物实验中证实应用TAICs可以在一定程度上特异性减轻排斥反应,使移植受者可以安全地减少传统免疫抑制剂的用量.

关键词：肾移植受者类巨噬细胞临床应用免疫干预耐受诱导制备方法 cells 免疫抑制剂

评价乳腺三维自动超声检查对提高致密型乳腺组织中乳腺癌检出率的价值:SomoInsight研究

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国际医学放射学杂志 2015年第3期 266-266页

作者： R.F.brem L.Tabár S.W.Duffy M.F.Inciardi j.A.Guingrich B.E.Hashimoto 李心海 Breast Imaging and Interventional Center George Washington University Medical Center2150 Pennsylvania Ave NWWashington DC 20037

目的明确与单独乳腺钼靶摄影检查比较联合应用乳腺三维自动超声和乳腺钼靶摄影检查对提高无症状致密型乳腺乳腺癌检出率的价值。方法本研究获得伦理委员

关键词：致密型乳腺乳腺癌检出癌检出率乳腺肿瘤 SomoInsight 乳腺钼靶摄影超声检查

采用3TMRI与DSA对一侧颅内硬脑膜动静脉瘘进行评估与临床治疗方案的制定:对时间分辨对比剂动态成像(TRICKS)与对比增强MR血管成像的详细分析

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国际医学放射学杂志 2017年第1期 110-110页

作者： L.Ertl H.Brückmann M.Kunz M.Patzig C.brem R.Forbrig 柴超 Department of Neuroradiology Institute of Clinical Radiology Ludwig-Maximilians-University Grosshadern Campus

摘要目的目前诊断一侧颅内硬脑膜动静脉瘘(LDAVF)的金标准是数字减影血管造影(DSA)。然而,MRI是评估这类疾病的一种无创性的工具。本研究的目的是将

关键词：硬脑膜动静脉瘘 MRI 治疗方案 DSA TRICKS 对比增强颅内血管成像 MR 对比剂时间分辨