The three forms of neutrophil gelatinase B -monomer, homodimer and monomer/lipocalin complex -, were isolated from phorbolester stimulated neutrophil granulocytes by chromatography on gelatin-Sepharose and heparin-Ultrogel. On average, about 50% of the monomer/lipocalin complex was found to be complexed with TIMP-1. After activation with trypsin monomer, homodimer and monomer/lipocalin complex displayed a specific activity of about 2000 mU/mg towards the substrate N-(2,4)-dinitrophenyl-Pro-GlnGly-lle-Ala-Gly-Gln-D-Arg, whereas the monomer/ lipocalin/TIMP-1 complex could be activated to a specific activity of only 200 mU/mg. The ternary monomer/lipocalin/TIMP-1 complex behaves like the progelatinase A-TIMP-2 complex and the progelatinase B-TIMP-1 complex in that it is an inhibitor for active metalloproteinases (MMPs) and, after activation, a gelatinase with a pronouncedly reduced activity. When the monomer/lipocalin/TIMP-1 complex inhibits an MMP, a quaternary complex monomer/lipocalin/TIMP-1/MMP is generated which after activation shows a sixfold higher proteolytic activity than the active ternary complex.
Zusammenfassung: Der Einfluß von Chlordiazepoxid (Librium) auf die gerinnungshemmende Aktivität von Phenprocoumon (Marcumar) wurde an Ratten untersucht. Es ließ sich feststellen, daß das Psychopharmakon weder bei seiner alleinigen Verabreichung noch bei gemeinsamer Applikation mit Phenprocoumon einen Einfluß auf dessen gerinnungshemmende Aktivität, noch auf die normale Prothrombinzeit ausübt.Die Prothrombinzeit verkürzt sich jedoch trotz anhaltender Zufuhr von Phenprocoumon nach Absetzung von Chlordiazepoxid. Studies on the interactions of Phenprocoumon with Chlordiazepoxide in ratsSummary: The influence of ChJordiazepoxide (Librium) on the anticoagulating activity of Phenprocoumon (Marcumar) was investigated in rats. It was found that this psychotropic drug influences neither the anticoagulating activity nor the normal prothrombin-time when it is applied alone or together with Phenprocoumon. However, the prothrombin-time is shortened when Chlordiazepoxide is withdrawn and the feeding of Phenprocoumon is continued. Einleitung
Zusammenfassung: Die Konstruktion sowie die wichtigsten technischen Einzelheiten und die Handhabung eines neuen Elektrophorese-Gerätes 1 ) werden hier angegeben. Das Gerät ermöglicht in einfacher Weise die Durchführung der Durchfluß-Elektrophorese sowie fast sämtlicher Elektrophorese-Techniken in Flach-und Rundgelen. Die Anwendbarkeit dieser Apparatur wird anhand einiger Trennungen, die mit Hilfe der Durchfluß-Elektrophorese ausgeführt wurden, gezeigt. % Flow-through electrophoresis Summary: The construction, the main technical details and the handling of a new electrophoretic apparatus 1 ) are described. This System can be used for flow-through electrophoresis, äs well äs all slab or tube gel techniques. The suitability of the apparatus is demonstrated by the electrophoretic analysis of different samples by flow-through electrophoresis. Einführung
Die EiweiBbindung von Phenprocoumon an menschliches Serumalbumin wurde durch kontinuierliche Ultrafiltration in den Konzentrationsbereichen (cm,) 1-7.5 . 10" mol . 1-' (Fluoreszenzdetektion) und 1.82-19.66 . l p mol . 1-' (UV-Detektion) gemessen. Der freie Anteil a ist bis zu einer Gesamtkonzentration von 3.5 . 1@ mol . 1-' nahezu konstant und betragt 0.5 %. Auch die ubrigen Parameter (n, = 2.3; ng = 4.7; k , = 33. 10-'mol. 1-'; AGO = -7.94 kcal . mol-I) stimmen mit Werten aus anderen Methoden recht gut uberein. Der Vorteil der beschriebenen Mcthode liegt in ihrer Schnelligkeit und der durch die groBe Zahl von MeBwerten bedingten Sicherheit der Auswertung.
Studies on the interaction of Phenprocoumon with Diazepam and with NitrazepamSummary: The influence of Diazepam and Nitrazepam on the anticoagulating activity of Phenprocoumon was studied in rats. It was found that the repeated oral application of Diazepam or Nitrazepam during the treatment with Phenprocoumon did not change the adjusted prothrombin time. The prothrombin time was considerably shortened when the application of Diazepam or Nitfazepam was stopped although Phenprocoumon was still applied.Furthermore, the influence of Chlordiazepoxid, Diazepam and Nitrazepam on the normal prothrombin time was studied. It was found that the treatment with benzodiazepine derivatives had no influence upon the prothrombin time, not only during the treatment, but also after the treatment was stopped.
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