Stanozolol-Induced Changes in Fibrinolysis and Coagulation in Healthy Adults

1984 ◽  
Vol 51 (02) ◽  
pp. 157-164 ◽  
Author(s):  
C Kluft ◽  
F E Preston ◽  
R G Malia ◽  
R M Bertina ◽  
G Wijngaards ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Protein C ◽  
Plasma Lipids ◽  
Therapeutic Potential ◽  
Healthy Adults ◽  
Tissue Type ◽  
Coagulation System ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Type Plasminogen Activator

SummaryThe effects of orally-administered stanozolol, 5 mg b. d. on fibrinolysis, coagulation and on various haematological and biochemical parameters have been studied in 16 healthy adults, 8 males and 8 females. Statistically significant enhancement of extrinsic (tissue-type) plasminogen activator activity was detected in all subjects studied. This was associated with significant increases in plasma plasminogen and a concomitant reduction in histidine-rich glycoprotein. There were no changes in plasma urokinase activity. Changes in the coagulation system included significant reduction in plasma fibrinogen and elevation of protein C and anti thrombin III. Changes in plasma lipids included significant reduction of HDL cholesterol associated with an increase in LDL triglycerides. No change occurred in total cholesterol. There were no major differences between the sexes, nor were there serious side effects.The effects of stanozolol on extrinsic (tissue-type) plasminogen activator activity, “free” plasminogen, protein C and antithrombin III, argue strongly in favour of its therapeutic potential.

Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: The role of the anhepatic period

Hepatology ◽  
1992 ◽  
Vol 16 (2) ◽  
pp. 404-408 ◽  
Author(s):  
C. Minke Bakker ◽  
Herold J. Metselaar ◽  
Theo N. Groenland ◽  
Maria J. Gomes ◽  
Eduard A. R. Knot ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Type Plasminogen Activator ◽  
Anhepatic Period

Influence of 1-Desamino-8-d-Vasopressin on Endogenous Fibrinolysis, Haemodynamics and Liver Blood Flow in Healthy Subjects

1994 ◽  
Vol 86 (5) ◽  
pp. 497-503 ◽  
Author(s):  
J. Burggraaf ◽  
H. C. Schoemaker ◽  
J. M. Kroon ◽  
L. Huisman ◽  
C. Kluft ◽  
...  
Keyword(s):  
Blood Flow ◽  
Confidence Interval ◽  
Indocyanine Green ◽  
Plasminogen Activator ◽  
Liver Blood Flow ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Type Plasminogen Activator ◽  
Fibrinolytic Parameters

1. Endogenous fibrinolytic capacity increases after administration of 1-desamino-8-d-vasopressin. This increase is commonly attributed to an increase in release of tissue-type plasminogen activator from the endothelium. However, the possibility that 1-desamino-8-d-vasopressin influences liver blood flow, which is a major determinant of tissue-type plasminogen activator clearance, cannot be ruled out. 2. The influence of 1-desamino-8-d-vasopressin on haemodynamics, liver blood flow and fibrinolytic parameters was investigated in a randomized double-blind cross-over study in nine healthy male subjects (age 20–26 years). 3. 1-Desamino-8-d-vasopressin exerted significant haemodynamic effects: mean arterial pressure decreased maximally 12 (95% confidence interval 8–15) mmHg and heart rate increased maximally 21 (95% confidence interval 15–27) beats/min. 4. Endogenous fibrinolytic parameters increased after administration of 1-desamino-8-d-vasopressin. Both tissue-type plasminogen activator antigen and tissue-type plasminogen activator activity were elevated and showed the maximal response shortly after drug administration was completed. 5. 1-Desamino-8-d-vasopressin increased portal venous blood flow as measured with echo-Doppler. The maximal increase in mean blood flow of 55 (95% confidence interval 19–92)% was observed at the end of the 1-desamino-8-d-vasopressin infusion and coincided with the maximal changes in systemic haemodynamics and fibrinolytic parameters. The increase in portal blood flow was not reflected in significant changes in Indocyanine Green clearance. It appears that the Indocyanine Green method is relatively insensitive to increases in liver blood flow. 6. The observed increase in fibrinolytic activity due to tissue-type plasminogen activator activity after 1-desamino-8-d-vasopressin administration may be due to an increased release of tissue-type plasminogen activator from the endothelium and is not caused by changes in clearance.

scholarly journals Tissue-Type Plasminogen Activator and Tenecteplase-Mediated Increase in Blood Brain Barrier Permeability Involves Cell Intrinsic Complement

2020 ◽  
Vol 11 ◽  
Author(s):  
Charithani B. Keragala ◽  
Trent M. Woodruff ◽  
Zikou Liu ◽  
Be'eri Niego ◽  
Heidi Ho ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Receptor Activation ◽  
Tissue Type ◽  
C5a Receptor ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Bbb Permeability

Background: Tissue-type plasminogen activator (t-PA) has been the mainstay of therapeutic thrombolysis for patients with acute ischaemic stroke (AIS). However, t-PA can cause devastating intracerebral hemorrhage. t-PA can also influence the CNS in part by modulation of BBB permeability. Complement activation also occurs after AIS and has also been reported to increase BBB permeability. The complement components, C3 and C5, can also be activated by t-PA via plasmin formation and cell intrinsic complement may be involved in this process. Tenecteplase (TNK-tPA) is a t-PA variant with a longer plasma half-life, yet the ability of TNK-tPA to modulate the BBB and complement is less clear.Aim: To evaluate the effect of C5 and C5a-receptor 1 (C5aR1) inhibitors on t-PA- and TNK-tPA-mediated opening of the BBB.Methods: We used an in vitro model of the BBB where human brain endothelial cells and human astrocytes were co-cultured on the opposite sides of a porous membrane assembled in transwell inserts. The luminal (endothelial) compartment was stimulated with t-PA or TNK-tPA together with plasminogen, in the presence of PMX205 (a non-competitive C5aR1 antagonist), Avacopan (a competitive C5aR1 antagonist) or Eculizumab (a humanized monoclonal inhibitor of human C5). BBB permeability was assessed 5 and 24 h later. Immunofluorescence was also used to detect changes in C5 and C5aR1 expression in endothelial cells and astrocytes.Results: PMX205, but not Avacopan or Eculizumab, blocked t-PA-mediated increase in BBB permeability at both the 5 and 24 h time points. PMX205 also blocked TNK-tPA-mediated increase in BBB permeability. Immunofluorescence analysis revealed intracellular staining of C5 in both cell types. C5aR1 expression was also detected on the cell surfaces and also located intracellularly in both cell types.Conclusion: t-PA and TNK-tPA-mediated increase in BBB permeability involves C5aR1 receptor activation from cell-derived C5a. Selective inhibitors of C5aR1 may have therapeutic potential in AIS.

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