The Anticoagulant Effect, Plasma Clearance and Metabolism of the Enantiomers of Warfarin in Man

1972 ◽  
Vol 43 (6) ◽  
pp. 15P-16P
Author(s):  
D. S. Hewick ◽  
J. McEwen
Keyword(s):  
Plasma Clearance ◽  
Anticoagulant Effect

scholarly journals Effect of furosemide on plasma clearance, anticoagulant effect and protein binding of warfarin in rats.

1982 ◽  
Vol 5 (10) ◽  
pp. 829-840 ◽  
Author(s):  
TARO OGISO ◽  
MASAHIRO IWAKI ◽  
YOSHIMASA KONISHI
Keyword(s):  
Protein Binding ◽  
Plasma Clearance ◽  
Anticoagulant Effect

scholarly journals Effect of digoxin on plasma clearance and anticoagulant effect of warfarin in rats.

1984 ◽  
Vol 7 (3) ◽  
pp. 186-194
Author(s):  
TARO OGISO ◽  
MASAHIRO IWAKI ◽  
YOSHIMASA KONISHI
Keyword(s):  
Plasma Clearance ◽  
Anticoagulant Effect

Catabolism of Human Fibrinogen Fragment D in Normal Subjects and Patients with Liver Cirrhosis

1980 ◽  
Vol 44 (03) ◽  
pp. 146-149 ◽  
Author(s):  
Nicole Ardaillou ◽  
Jeannine Yvart ◽  
Philippe Le Bras ◽  
Marie-José Larrieu
Keyword(s):  
Liver Cirrhosis ◽  
Clearance Rate ◽  
Plasma Clearance ◽  
Normal Subjects ◽  
Fractional Catabolic Rate ◽  
Human Fibrinogen ◽  
Plasma Pool ◽  
Catabolic Rate ◽  
Chloramine T

SummaryThe catabolism of human fragment D, (FgD), obtained by plasmin digestion of fibrinogen has been investigated in normal subjects and patients with liver cirrhosis and the results compared with those obtained for fibrinogen (Fg). Fg was labelled with I-125 and Fg D with I-131 using the chloramine T method. The plasma disappearance curves of both labelled proteins fitted a two exponential curve. In controls the plasma clearance rate of Fg D was greater than that of Fg as shown by the marked difference between the half-lives of these two tracers: 8,9 and 83,5 hours for Fg D and Fg respectively. The fractional catabolic rate of Fg D was 3.38 times the plasma pool per day. In nine patients with liver cirrhosis, catabolism of Fg was not modified. In contrast, catabolism of Fg D was significantly reduced with a half life of 13.0 hours and a low fractional catabolic rate. These results suggest the role of the liver in the catabolism of Fg D in man.

“In vitro” Neutralization with Oxalate Ion of the Anticoagulant Effect of Heparin

1961 ◽  
Vol 05 (02) ◽  
pp. 314-318 ◽  
Author(s):  
W. O Cruz ◽  
L Meis ◽  
C. P Dietrich
Keyword(s):  
Calcium Oxalate ◽  
Aluminium Hydroxide ◽  
Barium Sulfate ◽  
Anticoagulant Effect ◽  
Normal Plasma ◽  
Oxalate Ion

SummaryHeparinized blood or plasma coagulates if, after addition of oxalate, recalcification follows. Of the decalcifying agents only oxalate ion has been suitable for demonstrating this phenomenon. Oxalate seem to accomplish two different roles connected with this effect: a fundamental one, i. e., to sensitize a heparinlipoprotein complex to the action of an anti-heparin factor found in normal plasma or serum and a secondary one, related to its capacity to adsorb this antiheparin factor. The latter is removable by centrifugation. This anti-heparin oxalate factor, which is able to counteract the action of heparin after previous addition of oxalate, was found in sequestrened, Dowex 50 resin plasma or in serum, but is not active in citrated plasma. This factor was removed from plasma by adsorption with barium sulfate, aluminium hydroxide or calcium oxalate and was eluted from these adsorbants after incubation with saline.

Studies on Metabolism of Urokinase and Mechanism of Thrombolysis by Urokinase

1979 ◽  
Vol 42 (03) ◽  
pp. 885-894 ◽  
Author(s):  
Tatsuo Ueno ◽  
Norio Kobayashi ◽  
Tadashi Maekawa
Keyword(s):  
Molecular Weight ◽  
Plasma Clearance ◽  
Radioactive Material ◽  
Optimal Dosage ◽  
Plasma Clot ◽  
Optimal Dosage Regimen ◽  
Arterial Thrombus ◽  
Contact Experiment

SummaryPharmacokinetics of intravenously injected 125I-labeled urokinase (125I-UK) of a molecular weight of 33,000 daltons in normal rabbits and patients with various diseases were investigated. The plasma clearance of 125I-UK in rabbits was described by a biexponential curve within six hours with a half-life of 8 minutes, 2.3 hours, respectively. The radioactivity in the liver and kidneys 15 minutes after iv injection with 125I-UK was 9.6% and 14.0% of the radioactivity injected, respectively. Approximately 80% of the total radioactive material injected was excreted in the urine in 18 hours. No increase in activator activity in the urine was observed after a large amount of UK injection. Activity uptake of 125I-UK by experimentally induced arterial thrombus was little. Lysis of the stasis thrombus was produced by injecting 7.5 × 104 IU of UK in only one out of 8 rabbits. In vitro contact experiment revealed that transfer of 125I-UK to plasma clot is slow (24 hours for 10% of 125I-UK by plasma clot). In 4 patients plasma clearance of 125I-UK was essentially similar to that in rabbits. From the results obtained optimal dosage regimen of UK administration for complete thrombolysis in vivo was discussed.

scholarly journals The Insulin Receptor Mediates Insulin’s Early Plasma Clearance by Liver, Muscle, and Kidney

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Rick I. Meijer ◽  
Eugene J. Barrett
Keyword(s):  
Insulin Receptor ◽  
Plasma Clearance ◽  
Plasma Insulin ◽  
Insulin Clearance ◽  
Initial Plasma ◽  
Liver And Kidney ◽  
Pre Treatment ◽  
Initial Clearance

The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([125I]TyrA14)-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([125I]TyrA14)insulin concentration approximately 5-fold (p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle (p < 0.01), liver (p < 0.05), and kidney (p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance (p = 0.056) while increasing renal clearance by >50% (p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.

scholarly journals Catalytic activity and stereoselectivity of engineered phosphotriesterases towards structurally different nerve agents in vitro

2021 ◽  
Author(s):  
Anja Köhler ◽  
Benjamin Escher ◽  
Laura Job ◽  
Marianne Koller ◽  
Horst Thiermann ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Nerve Agents ◽  
Inhibition Assay ◽  
Ache Inhibition ◽  
Catalytic Activities ◽  
Chiral Lc ◽  
Hydrolysis Of ◽  
Medical Countermeasures

AbstractHighly toxic organophosphorus nerve agents, especially the extremely stable and persistent V-type agents such as VX, still pose a threat to the human population and require effective medical countermeasures. Engineered mutants of the Brevundimonas diminuta phosphotriesterase (BdPTE) exhibit enhanced catalytic activities and have demonstrated detoxification in animal models, however, substrate specificity and fast plasma clearance limit their medical applicability. To allow better assessment of their substrate profiles, we have thoroughly investigated the catalytic efficacies of five BdPTE mutants with 17 different nerve agents using an AChE inhibition assay. In addition, we studied one BdPTE version that was fused with structurally disordered PAS polypeptides to enable delayed plasma clearance and one bispecific BdPTE with broadened substrate spectrum composed of two functionally distinct subunits connected by a PAS linker. Measured kcat/KM values were as high as 6.5 and 1.5 × 108 M−1 min−1 with G- and V-agents, respectively. Furthermore, the stereoselective degradation of VX enantiomers by the PASylated BdPTE-4 and the bispecific BdPTE-7 were investigated by chiral LC–MS/MS, resulting in a several fold faster hydrolysis of the more toxic P(−) VX stereoisomer compared to P(+) VX. In conclusion, the newly developed enzymes BdPTE-4 and BdPTE-7 have shown high catalytic efficacy towards structurally different nerve agents and stereoselectivity towards the toxic P(−) VX enantiomer in vitro and offer promise for use as bioscavengers in vivo.

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