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| 1 | Clopidogrel and proton pump inhibitors-where do we stand in 2012?显示文摘Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended. | Michael D Drepper Laurent Spahr Jean Louis Frossard | 2012 | World Journal of Gastroenterology2012，18，18： | 8 |
| 2 | Rapid generation of recombinant Pseudomonas putida secondary metabolite producers using yTREX显示文摘Microbial secondary metabolites represent a rich source of valuable compounds with a variety of applications in medicine or agriculture.Effective exploitation of this wealth of chemicals requires the functional expression of the respective biosynthetic genes in amenable heterologous hosts.We have previously established the TREX system which facilitates the transfer,integration and expression of biosynthetic gene clusters in various bacterial hosts.Here,we describe the yTREX system,a new tool adapted for one-step yeast recombinational cloning of gene clusters.We show that with yTREX,Pseudomonas putida secondary metabolite production strains can rapidly be constructed by random targeting of chromosomal promoters by Tn5 transposition.Feasibility of this approach was corroborated by prodigiosin production after yTREX cloning,transfer and expression of the respective biosynthesis genes from Serratia marcescens.Furthermore,the applicability of the system for effective pathway rerouting by gene cluster adaptation was demonstrated using the violacein biosynthesis gene cluster from Chromobacterium violaceum,producing pathway metabolites violacein,deoxyviolacein,prodeoxyviolacein,and deoxychromoviridans.Clones producing both prodigiosin and violaceins could be readily identified among clones obtained after random chromosomal integration by their strong color-phenotype.Finally,the addition of a promoter-less reporter gene enabled facile detection also of phenazine-producing clones after transfer of the respective phenazine-1-carboxylic acid biosynthesis genes from Pseudomonas aeruginosa.All compounds accumulated to substantial titers in the mg range.We thus corroborate here the suitability of P.putida for the biosynthesis of diverse natural products,and demonstrate that the yTREX system effectively enables the rapid generation of secondary metabolite producing bacteria by activation of heterologous gene clusters,applicable for natural compound discovery and combinatorial biosynthesis. | Andreas Domrose Robin Weihmann Stephan Thies Karl-Erich Jaeger Thomas Drepper Anita Loeschcke | 2017 | Synthetic and Systems Biotechnology2017，2，4： | 2 |
| 3 | PTEN depletion rescues axonal growth defect and improves survival in SMN-deficient motor neurons显示文摘 | Ning K Drepper C Valori CF | 2010 | Hum Mol Genet2010，16，： | 1 |
| 4 | Use of sequence information in associative learning in control subjects and cerebellar patients显示文摘 | Timmarm D Drepper J Calabrese S | | 0，，： | 1 |
| 5 | A calcium-gated lid and a large -roll sandwich are revealed by the crystal structure of extracellular lipase from Serratia marcescens显示文摘 | Meier R Drepper T Svensson V | 2007 | J Biol Chem2007，282，31： | 1 |
| 6 | Chance and chaos in population biology-models of recurrent epidemics raid food chain dynamics显示文摘 | Engbert R Drepper F R | 1994 | Chaos Solitons and Fractals1994，4，： | 1 |
| 7 | The Hfq-like protein NrfA of the phototrophic purple bacterium Rhodobacter capsulatus controls nitrogen fixation via regulation of nifA and anfA expression 显示文摘 | Drepper T Raabe K Giaourakis D | 2002 | FEMS Microbiology Letters2002，2，： | 1 |
| 8 | Technical note on VDS: A system for the endovascular electrolytical detachment of platinum coils at variable length 显示文摘 | Henkes H Drepper P Speder J | 2002 | Intervent Neuroradiol2002，8，2： | 1 |
| 9 | Reporter proteins for in vivo fluorescence without oxygen 显示文摘 | Drepper T Eggert T Cireolone F | 2007 | Nat Bioteehnol2007，25，4： | 1 |
| 10 | Effect of functional NMDA-antagonist flupirtine on automatic postural responses in Parkinson's disease显示文摘 | Putzki N Maschke M Drepper J | 2002 | J Neurol2002，249，7： | 1 |
| 11 | Novel biocatalysts for white biotechnology 显示文摘 | DREPPER T EGGERT T HUMMEL W | 2006 | Biotechnology Journal2006，1，78： | 1 |
| 12 | From model compounds to protein binding:syntheses,characterizations and fluorescence studies of 2+ complexes(bipy=2,2;-bipyridine;terpy=2,2':6'2'-terpyridine;L=imidazole,pyrazole and derivatives,cytochrome c)显示文摘 | YANG X J DREPPER F WU B | 2005 | Dalton Transactions2005，2，： | 1 |
| 13 | Chance and chaos in population biology models of recurrent epidemics and food chain dynamics显示文摘 | Engbert R Drepper F | 1994 | Chaos Solitons & Fractals1994，4，： | 1 |
| 14 | Isolation and enrichment of embryonic mouse motoneurons from the lumbar spinal cord of individual mouse embryos显示文摘 | WIESE S HERRMANN T DREPPER C | 2010 | Nat Protoc2010，5，1： | 1 |
| 15 | New blood derived protein products for food use 显示文摘 | Drepper G Drepper K Ludwig- Buseh H | 1981 | Proceedings European Meeting Meat Research Workers1981，27，11： | 1 |
| 16 | Overview of peritoneal dialysis显示文摘 | Laperrousaz S Drepper VJ | 2016 | Rev Med Suisse2016，12，507： | 1 |
| 17 | A calcium-gat- ed lid and a large 显示文摘 | MEIER R DREPPER T SVENSSON V | 2007 | Biological Chemsty2007，282，31： | 1 |
| 18 | Effect of functional NMDA-antagonist flupirtine on automatic postural responses in Parkinson's disease显示文摘 | Putzki N Maschke M Drepper J | 2002 | J Neurol2002，249，7： | 1 |
| 19 | Formation of acarbosephosphat e byacell-free extract from the acarbosrproducer Actinoplanes sp显示文摘 | Goeke K Drepper A Pape H | | 0，，7： | 1 |
| 20 | Use of sequence information in associative learning in control subjects and cerebel ar patients显示文摘 | Timmarn D Drepper J Calabrese S | | 0，，： | 1 |
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