The interaction of protamine with human blood plasma proteins

Zusammenfassung Es wurden Interaktionen von Protamin mit vorher in Agar-Gel elektrophoretisch getrennten plasmatischen Eiweisskörpern untersucht. Neben der schon früher bekannten Interaktion mit Fibrinogen wurden auch solche mit beiden Klassen der plasmatischen Lipoproteine gefunden.     

Radioimmunoassay of angiotensin II in rat plasma

Zusammenfassung Eine radioimmunologische Methode zur direkten Bestimmung von Angiotensin II aus 50 l arteriellem Rattenplasma wird beschrieben. Der Normalwert beträgt 86.8 pg/ml±24.8 S.D. (n=29). Nach kochsalzarmer Ernährung nahm die Angiotensin-II-Konzentration im Plasma stark zu, während sie nach DOCA und Salzgabe deutlich abfiel (p<0.001).

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Acknowledgment. We wish to thank Mr.H. Dick for his skilful technical assistance.     

In vitro amiodarone protein binding and its interaction with warfarin

Summary The binding of amiodarone to human plasma protein and to bovine serum, albumin was studied by three different methods, ultracentrifugation, equilibrium dialysis and fluorescence spectroscopy. The fraction of amiodarone bound to plasma protein amounted to 96.3%. The changes in the binding properties of 1-anilino-naphthalene-8-sulfonate for bovine serum albumin using warfarin and amiodarone as independent inhibitors were analyzed in terms of binding site specificity. The findings indicated that amiodarone and warfarin have two different binding sites on bovine serum albumin, so a noncompetitive inhibition mechanism was indicated. On the basis of our data we cannot exclude other mechanisms of interaction besides direct displacement of one drug by another; nevertheless, metabolite interference between amiodarone and coagulation cofactors may better explain the enhancement of warfarin's pharmacological action in association with amiodarone.This work was partially funded by the CNR (National Research Council, Rome, Italy), Program on Clinical Pharmacology and Rare Diseases. The authors would like to thanks Drs E. Marzi and E. riva for their help.     

In vitro amiodarone protein binding and its interaction with warfarin

The binding of amiodarone to human plasma protein and to bovine serum albumin was studied by three different methods, ultracentrifugation, equilibrium dialysis and fluorescence spectroscopy. The fraction of amiodarone bound to plasma protein amounted to 96.3%. The changes in the binding properties of 1-anilino-naphthalene-8-sulfonate for bovine serum albumin using warfarin and amiodarone as independent inhibitors were analyzed in terms of binding site specificity. The findings indicated that amiodarone and warfarin have two different binding sites on bovine serum albumin, so a noncompetitive inhibition mechanism was indicated. On the basis of our data we cannot exclude other mechanisms of interaction besides direct displacement of one drug by another; nevertheless, metabolite interference between amiodarone and coagulation cofactors may better explain the enhancement of warfarin's pharmacological action in association with amiodarone.     

Specific binding of 3H-progesterone to a plasma protein in the guinea pig fetus]

The presence of a protein that binds specifically and with high affinity to progesterone is found in the plasma of fetal guinea Pig. Progesterone and 5 alpha-dihydroxyprogesterone strongly compete for the 3H-progesterone-protein complex. 5 beta-dihydroxy progesterone, 20 beta-dihydroxyprogesterone, testosterone and synthetic progestagen, R-5020 (17,21-dimethyl-19-norpregna-4, 9-diene-3,20 dione), also compete but less intensely. 17-hydroxyprogesterone, aldosterone, cortisol, oestradiol and oestrone have no effect. The 3H-progesterone-protein, complex has an affinity of Kd = 8.8 +/- 3.5 x 10(-10) M and in sucrose density gradient the sedimentation coefficient is 4.6 S.     

Sex hormones as a factor controlling the blood plasma arylesterase activity in rats

Summary A rapid decrease in arylesterase activity was caused by the administration of estradiol to rats, followed by an increase to activity levels 100% higher than the starting levels. After this double response it required almost 40 days for the activity to return to normal levels. There was no remarkable effect by a long-term treatment with a preparation of prolonged estrogenic effect. The results presented further support previous findings that the arylesterase activity is under the control of steroid hormones.

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Zusammenfassung Zufuhr von Östradiol bedingte bei Ratten eine rasche Verminderung der Aktivität der Arylesterase, gefolgt von einer Aktivitätszunahme, die etwa 100% höher lag als die ursprünglichen Werte. Nach erfolgter doppelter Antwort dauerte es fast 40 Tage bevor die Enzymaktivität die normale Höhe wieder erreichte. Dadurch werden frühere Befunde bestätigt, wonach die Arylesteraseaktivität durch Steroidhormone reguliert wird.

     

Evidence for the nonhydrophobic interaction of aromatic,nitrogen-containing compounds with the coenzyme binding site of a NAD-linked D-lactate dehydrogenase

Summary Quantitative structure activity relationships suggest that the binding of quinoline and phenanthroline analogs to D-lactate dehydrogenase from the barnacle,Balanus nubilus Darwin, does not involve primarily hydrophobic effects. This phenomenon appears to exist also for other lactate dehydrogenases.We thank C. Hansch for advice regarding QSAR studies. Supported by U.S.P.H.S. (GM-22868-01) to GLL.     

Increased plasma fibrinogen and the release of a fibrinogen enhancing factor in tumour-bearing rats

Zusammenfassung Die Freisetzung eines die Fibrinogensynthese stimulierenden Faktors aus nekrotischem Gewebe in die Blutbahn ist für den Anstieg des Plasmafibrinogens bei experimentellen Rattentumoren verantwortlich.     

Effects of intracerebroventricular injections of angiotensin II on prolactin plasma levels in the Rhesus monkey

Summary Intracerebroventricular injections of angiotensin II (A II) induced a sharp and dose-dependent increase in plasma prolactin (PRL) levels in the awake Rhesus monkey. Our results suggest that in primates, A II may be involved in the mechanisms controlling PRL secretion.Acknowledgments. We thank Mrs. J. Arsaut and D. Verrier for excellent technical assistance. This work was supported by grants from INSERM (CRL No. 78.1.2656), DGRST (77.7.9654) and CNRS (ERA 493).     

An actin-destabilizing factor is present in human plasma

Summary Plasma and serum of humans or experimental animals contain a factor which destabilizes F-actin. The factor has no DNAse or thrombin activity and after incubation with F-actin does not modify the position of the actin band on a SDS polyacrylamide gel. Hence it probably depolymerizes F-actin.Acknowledgment. This work was supported by the Swiss National Science Foundation, grant No.3.692-0.76. We thank Drs M. Crippa and C.A. Bouvier for measuring the DNAse and thrombin activities. The technical help of Mrs M. Redard and A. De Almeida and the photographic work of Mr J.-C. Rumbeli and Mr E. Denkinger are gratefully acknowledged.     

Evidence for the nonhydrophobic interaction of aromatic, nitrogen-containing compounds with the coenzyme binding site of a NAD-linked D-lactate dehydrogenase.

Quantitative structure activity relationships suggest that the binding of quinoline and phenanthroline analogs to D-lactate dehydrogenase from the barnacle, Balanus nubilus Darwin, does not involve primarily hydrophobic effects. This phenomenon appears to exist also for other lactate dehydrogenases.     

An actin-destabilizing factor is present in human plasma.

Plasma and serum of humans or experimental animals contain a factor which destabilizes F-actin. The factor has no DNAse or thrombin activity and after incubation with F-actin does not modify the position of the actin band on a SDS polyacrylamide gel. Hence it probably depolymerizes F-actin.     

The interaction of warfarin with antacid constituents in the gut

Summary A study was made of the effect of 4 constituents of antacid preparations on the absorption of the coumarin derivate warfarin sodium using an in vitro experimental model. The constituents tested were activated dimethicone (a silicone) magnesium trisilicate, bismuth carbonate and the adsorbant, kaolin. Slight decreased intestinal absorption was shown by magnesium trisilicate (19%) and bismuth carbonate (7%), the other 2 components showing no effects.