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  • Cdc7 kinase  (1)
  • Key words Anticoagulation – phenprocoumon – antidepressants – drug-drug interaction  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Zeitschrift für Herz-, Thorax- und Gefässchirurgie 13 (1999), S. 139-146 
    ISSN: 0930-9225
    Keywords: Schlüsselwörter Antikoagulantien – Phenprocoumon – Antidepressiva – Arzneimittelinteraktion ; Key words Anticoagulation – phenprocoumon – antidepressants – drug-drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A potential impact of tricyclic antidepressants on oral anticoagulation is controversial. Phenprocoumon – the most commonly used anticoagulant in Germany – is rarely considered in clinical trials. In the present study, a potential drug-drug interaction between phenprocoumon and tricyclics, causing an alteration in prothrombinemic effects, has been investigated. In eleven patients simultaneously receiving tricyclic antidepressants and phenprocoumon the course of Quick values and the phenprocoumon dosages were compared to a control group of eleven phenprocoumon treated patients not receiving tricyclics. Quick value deviations from the individually required therapeutic ranges 〉25%, as well as frequent changes in the phenprocoumon dosages were indicators of an inconstant oral anticoagulation and a possible interaction. The results showed unstable prothrombinemic effects throughout tricyclic antidepressant therapy. The average Quick value deviation amounted to 68.7% in the patients group and to 13.1% in the control group. Additionally, there was an average change in phenprocoumon dosage of 0.6 in the patients group and of 0.2 in the control group. Further controlled studies are certainly warranted to specifically answer the question of a clinically relevant drug-drug interaction.
    Notes: Zusammenfassung Eine mögliche Beeinflussung der Antikoagulanzientherapie durch trizyklische Antidepressiva wird bislang unterschiedlich bewertet. Vor allem das in Deutschland therapeutisch eingesetzte Antikoagulanz Phenprocoumon bleibt bei Untersuchungen nahezu unberücksichtigt. Die vorliegende retrospektive Studie wurde unter der Fragestellung einer potentiellen Arzneimittelinteraktion zwischen Phenprocoumon und Trizyklika durchgeführt. Bei 11 gleichzeitig mit Trizyklika und Phenprocoumon behandelten Patienten und 11 antikoagulierten Kontrollen ohne antidepressive Therapie erfolgte eine Gegenüberstellung von Quickwertverlauf und Phenprocoumondosis während und außerhalb trizyklischer Therapie. Quickwertabweichungen vom therapeutischen Bereich 〉25% und häufige Phenprocoumon-Dosiswechsel galten als Zeichen einer instabilen Antikoagulation und einer zugrundeliegenden Interaktion. Sowohl im intraindividuellen Patientenvergleich wie auch in der Gegenüberstellung von Patienten- und Kontrollkollektiv wurde eine instabile Phenprocoumonwirkung unter Trizyklikatherapie gezeigt. Die mittlere Quickwertabweichung [mQWA] betrug im Patientenkollektiv 68,7%, im Kontrollkollektiv 13,1%. Für das Patientenkollektiv wurde eine mittlere Dosiswechselzahl [mDWZ] von 0,6 errechnet. Im Kontrollkollektiv lag die mDWZ bei 0,2. Inwiefern unsere Beobachtungen als Indikator einer potentiellen Arzneimittelinteraktion gelten können, ist in diesem Rahmen nicht abschließend zu beurteilen. Zur endgültigen Abklärung der Fragestellung erscheint die Durchführung prospektiver Studien angezeigt.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1617-4623
    Keywords: Key words Mammalian Dbf4 ; Cdc7 kinase ; MCM2 ; Initiation of DNA replication ; Cell cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The kinase Dbf4p/Cdc7p is required for the G1/S phase transition during the cell cycle and plays a direct role in the activation of individual origins of replication in Saccharomyces cerevisiae. Here, we report the identification and characterization of mouse and human cDNAs whose products are related in sequence to Saccharomyces cerevisiae DBF4 cDNA. Both mammalian Dbf4 proteins contain a putative site for phosphorylation by CDK, PEST protease cleavage sites, nuclear localization signals and a short-looped zinc finger-like domain. Transcription of MmDBF4 is suppressed in mouse NIH3T3 fibroblasts made quiescent by serum starvation. Upon replenishment of the medium, transcript levels increase during progression through G1, peaking as cells enter S phase. MmDbf4p interacts physically with Cdc7p and Mcm2p in vivo. Using fluorescence in situ hybridization (FISH), the human DBF4 gene was localized to chromosome 7 (q21.3), whereas FISH mapped the murine counterpart to band A2 on chromosome 5. The results of chromosome mapping indicate that in both mouse and human the gene is present as a single copy. The structural conservation between Dbf4-related proteins suggests that these proteins play a key role in the regulation of DNA replication during the cell cycle in all eukaryotes.
    Type of Medium: Electronic Resource
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