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  • CYP2C9; cytochrome-P-450  (1)
  • GPI-Linked Proteins/genetics  (1)
  • 2015-2019  (1)
  • 1995-1999  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 49 (1996), S. 305-308 
    ISSN: 1432-1041
    Keywords: Key words Lornoxicam ; CYP2C9; cytochrome-P-450 ; drug metabolism ; NSAIDs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: The nature of the enzyme(s) catalysing the biotransformation of lornoxicam to one of its major metabolites, 5′-hydroxy-lornoxicam, has been investigated in human liver microsomes. The reaction kinetics were characterised, the affinity of lornoxicam for three major human drug metabolising cytochrome P-450 isozymes (CYP2C9, CYP2D6 and CYP3A4) was determined, and inhibition of the reaction by known substrates (diclofenac, ibuprofen, mefenamic acid, phenytoin, tolbutamide and warfarin) and the prototype inhibitor (sulphaphenazole) of CYP2C9 was investigated. Results: Lornoxicam 5′-hydroxylation displayed single enzyme Michaelis-Menten kinetics, with a KM of 3.6 μmol⋅l−1 and a Vmax of 2.6 nmol ⋅h−1 ⋅mg−1  microsomal protein. The apparent affinity of lornoxicam was high for CYP2C9, but negligible for CYP3A4 and CYP2D6. Inhibition of lornoxicam 5′-hydroxylation by CYP2C9 substrates and sulphaphenazole was comparable in all livers preparations, values predicted from their KM or Ki for CYP2C9 determined in separate studies assuming competitive inhibition. Sulphaphenazole competitively and completely inhibited lornoxicam 5′-hydroxylation (Ki = 0.31 μmol ⋅l−1) as well as lornoxicam clearance (Ki = 0.33 μmol ⋅l−1), partial metabolic clearance (fm) = 0.95). Conclusion: 5′-Hydroxylation appears to be the only cytochrome P-450 catalysed metabolic reaction of lornoxicam by human liver microsomes and this major in vivo biotransformation pathway is catalysed virtually exclusively by CYP2C9.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2016-03-05
    Description: During corticogenesis, excitatory neurons are born from progenitors located in the ventricular zone (VZ), from where they migrate to assemble into circuits. How neuronal identity is dynamically specified upon progenitor division is unknown. Here, we study this process using a high-temporal-resolution technology allowing fluorescent tagging of isochronic cohorts of newborn VZ cells. By combining this in vivo approach with single-cell transcriptomics in mice, we identify and functionally characterize neuron-specific primordial transcriptional programs as they dynamically unfold. Our results reveal early transcriptional waves that instruct the sequence and pace of neuronal differentiation events, guiding newborn neurons toward their final fate, and contribute to a road map for the reverse engineering of specific classes of cortical neurons from undifferentiated cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Telley, Ludovic -- Govindan, Subashika -- Prados, Julien -- Stevant, Isabelle -- Nef, Serge -- Dermitzakis, Emmanouil -- Dayer, Alexandre -- Jabaudon, Denis -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1443-6. doi: 10.1126/science.aad8361. Epub 2016 Mar 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Neurosciences, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Genetic Medicine and Development, University of Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Genetic Medicine and Development, University of Geneva, Switzerland. Biomedical Research Foundation Academy of Athens, Greece. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Saudi Arabia. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Basic Neurosciences, University of Geneva, Switzerland. Department of Psychiatry, Geneva University Hospital, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. ; Department of Basic Neurosciences, University of Geneva, Switzerland. Clinic of Neurology, Geneva University Hospital, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Switzerland. denis.jabaudon@unige.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26940868" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cerebral Ventricles/cytology/embryology ; DNA-Binding Proteins/genetics ; Female ; GPI-Linked Proteins/genetics ; Green Fluorescent Proteins/genetics ; Male ; Mice ; Neocortex/cytology/*embryology ; Nerve Tissue Proteins/genetics ; Neural Stem Cells/cytology ; Neurogenesis/*genetics ; Neurons/*cytology ; Neuropeptides/genetics ; SOXB1 Transcription Factors/genetics ; *Transcription, Genetic ; Transcriptome
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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