scholarly journals Vampire Bat Plasminogen Activator DSPA-Alpha-1 (Desmoteplase): A Thrombolytic Drug Optimized by Natural Selection

2001 ◽  
Vol 31 (3-6) ◽  
pp. 118-122 ◽  
Author(s):  
Wolf-Dieter Schleuning
Keyword(s):  
Natural Selection ◽  
Plasminogen Activator ◽  
Thrombolytic Drug ◽  
Vampire Bat

Vampire Bat Salivary Plasminogen Activator Evokes Minimal Bleeding Relative to Tissue-Type Plasminogen Activator as Assessed by a Rabbit Cuticle Bleeding Time Model

1995 ◽  
Vol 73 (03) ◽  
pp. 478-483 ◽  
Author(s):  
Michael J Mellott ◽  
Denise R Ramjit ◽  
Inez I Stabilito ◽  
Timothy R Hare ◽  
Edith T Senderak ◽  
...  
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Intravenous Administration ◽  
Bleeding Time ◽  
Bleeding Risk ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Plasma Factor ◽  
Vampire Bat

SummaryCuticle bleeding time (CBT) measurements in anesthetized rabbits were performed to assess the potential bleeding risks which may accompany the administration of tissue-type plasminogen activator (tPA) or vampire bat salivary plasminogen activator (BatPA). The dose of BatPA or tPA used in this study, 42 nmol/kg, was previously shown to be efficacious using a rabbit femoral artery thrombosis model (Gardell et al, Circulation 84:244, 1991). CBT was determined by severing the apex of the nail cuticle and monitoring the time to cessation of blood flow. CBT was minimally elevated (1.6-fold, p<NS) following bolus intravenous administration of BatPA; in contrast, bolus intravenous administration of tPA dramatically elevated CBT (6.2-fold, p<0.05). Rabbits treated with tPA, but not BatPA, displayed profound activation of systemic plasminogen and consequent degradation of Factor VIII and fibrinogen. Elevations in CBT after the administration of tPA were reversed by the replenishment of plasma Factor VIII activity to 40% of control, but were unaffected by complete replenishment of plasma fibrinogen. The results of this study suggest that the administration of BatPA, at a dose that promotes thrombolysis, may evoke a minimal bleeding risk, relative to an equi-efficacious dose of tPA. In addition, the tPA-provoked proteolytic consumption of Factor VIII may be a key contributor to the heightened bleeding risk.

Vampire Bat Salivary Plasminogen Activator Promotes Robust Lysis of Plasma Clots in a Plasma Milieu Without Causing Fluid Phase Plasminogen Activation

1992 ◽  
Vol 68 (02) ◽  
pp. 165-169 ◽  
Author(s):  
Timothy R Hare ◽  
Stephen J Gardell
Keyword(s):  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fluid Phase ◽  
Immunoblot Analysis ◽  
Tissue Type ◽  
Clot Lysis ◽  
Plasma Clot ◽  
Type Plasminogen Activator ◽  
Iodine 125 ◽  
Vampire Bat

SummaryVampire bat salivary plasminogen activator (BatPA), human tissue-type plasminogen activator (tPA) or streptokinase (SK) were incubated in human citrated plasma containing a plasma clot that was radiolabelled with iodine-125 fibrin(ogen). Complete clot dissolution by BatPA (30 nM) was associated with slight activation of “fluid phase” plasminogen; the plasma levels of functional fibrinogen and α2-antiplasmin decreased by only 8 and 19%, respectively. Addition of SK (3,600 IU/ml) to the clot-containing plasma caused complete clot lysis and massive activation of the “fluid phase” plasminogen, leading to >60 and 96% decreases of the functional levels of fibrinogen and α2-antiplasmin, respectively. Incubation of tPA (30 nM) in clot-containing plasma caused complete clot lysis as well as substantial activation of “fluid phase” plasminogen; the plasma levels of functional fibrinogen and α2-antiplasmin decreased by 45 and 79%, respectively. The profound degradation of fibrinogen in the SK and tPA but not BatPA-containing samples was confirmed by immunoblot analysis. Additional experiments showed that the presence of soluble clot lysate in plasma containing tPA enhanced the extent of fibrinogen degradation from 25% to >60%; the addition of soluble clot lysate to the plasma containing BatPA did not prompt further fibrinogen degradation. Finally, studies using exogenous α2-antiplasmin suggested that plasmin generated via tPA-mediated activation of “fluid phase” plasminogen does not play an important role in clot dissolution.

Study on the therapeutic and nursing effect of thrombus targeted thrombolysis mediated by recombinant plasminogen activator modified nanoparticles on stroke patients

2021 ◽  
Vol 11 (7) ◽  
pp. 1024-1030
Author(s):  
Li Zhang ◽  
Miao Xu ◽  
Min Zhu ◽  
Andong Liu ◽  
Fenghua Zhao
Keyword(s):  
Drug Therapy ◽  
Plasminogen Activator ◽  
Survival Rates ◽  
Clinical Applications ◽  
The Self ◽  
Therapeutic Effects ◽  
Stroke Patients ◽  
Traditional Treatment ◽  
Thrombolytic Drug ◽  
Tissue Plasminogen

Tissue plasminogen activator (rt-PA) is a thrombolytic drug used for the treatment of stroke. However, it has a short half-life and a high risk of complications of cerebral hemorrhage, which complicates its use in clinical applications. In this study, polyethylene glycol and polycaprolactone were used as nano-carriers in the development of new nano-drug-recombinant plasminogen activator modified nanoparticles (PEG-PCL@rt-PA) loaded with rt-PA. Following treatment, the patients received with either conventional nursing or continuous nursing. Compared with traditional treatment and nursing, the nanoparticles had stronger thrombolytic and therapeutic effects, significantly improved the self-care recovery rate of patients, and reduced the occurrence of complications. This new mode of PEG-PCL@rt-PA drug therapy combined with continuous nursing is expected to improve the recovery and survival rates of stroke patients.

scholarly journals Tenecteplase for the treatment of acute ischemic stroke: A review of completed and ongoing randomized controlled trials

2018 ◽  
Vol 13 (9) ◽  
pp. 885-892 ◽  
Author(s):  
Shelagh B Coutts ◽  
Eivind Berge ◽  
Bruce CV Campbell ◽  
Keith W Muir ◽  
Mark W Parsons
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Genetically Engineered ◽  
Bolus Administration ◽  
Thrombolytic Drug ◽  
Tissue Plasminogen ◽  
Activator Inhibitor ◽  
Stroke Trial

Alteplase has been the mainstay of thrombolytic treatment since the National Institutes of Neurological Disorders and Stroke trial was published in 1995. Over recent years, several trials have investigated alternative thrombolytic agents. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, allowing single intravenous bolus administration without infusion, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor compared to alteplase. Tenecteplase is established as the first-line intravenous thrombolytic drug for myocardial infarction, where it has been shown to achieve comparable reperfusion with reduced risk of systemic bleeding in comparison to alteplase. We review the literature on tenecteplase for the treatment of acute ischemic stroke, with a focus on the major completed and ongoing trials. Overall, tenecteplase shows promise for treatment of acute ischemic stroke, both in populations currently eligible for alteplase and also in groups not currently treated with thrombolysis.

scholarly journals Thrombolytic properties of Desmodus rotundus (vampire bat) salivary plasminogen activator in experimental pulmonary embolism in rats

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1213-1217
Author(s):  
W Witt ◽  
B Baldus ◽  
P Bringmann ◽  
L Cashion ◽  
P Donner ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Desmodus Rotundus ◽  
Type Plasminogen Activator ◽  
Blood Clots ◽  
Hemostatic Factors ◽  
The Difference ◽  
Vampire Bat

rDSPA alpha 1 (recombinant Desmodus salivary plasminogen activator alpha 1) is a recombinant protein corresponding to a natural plasminogen activator from the vampire bat Desmodus rotundus. The thrombolytic properties of rDSPA alpha 1 and tissue-type plasminogen activator (t-PA) were compared in a rat model of pulmonary embolism. Whole blood clots, produced in vitro and labeled with 125I-fibrinogen, were embolized into the lungs of anesthetized rats. Thrombolysis was calculated from the difference between initial clot radioactivity and that remaining in the lungs at 60 minutes. Blood was sampled for gamma counting, measurement of hemostatic factors, and plasminogen activator antigen levels. Thrombolysis at 3, 10, 30, and 100 nmol/kg intravenously (10% bolus, 90% over 60 minutes) amounted to 30% +/- 2%, 51% +/- 4%, 85% +/- 4%, 98% +/- 0% for rDSPA alpha 1 and 30% +/- 3%, 41% +/- 3%, 57% +/- 6%, 93% +/- 2% for t-PA (controls: 29% +/- 2%; mean +/- SEM, n greater than or equal to 6). t-PA at 100 nmol/kg significantly decreased fibrinogen, plasminogen, and alpha 2- antiplasmin levels by 33% +/- 7%, 38% +/- 8%, and 61% +/- 9%, whereas rDSPA alpha 1 at 100 nmol/kg only lowered alpha 2-antiplasmin significantly (by 29% +/- 6%). Compared with t-PA, rDSPA alpha 1 is the more potent and more clot selective (fibrin specific) thrombolytic agent. These results suggest that rDSPA alpha 1 may be safer and more efficacious than currently used thrombolytics.

Production of vampire bat plasminogen activator DSPA α1 in CHO and insect cells

1995 ◽  
Vol 39 (1) ◽  
pp. 75-83 ◽  
Author(s):  
T. Petri ◽  
G. Langer ◽  
P. Bringmann ◽  
L. Cashion ◽  
S. Shallow ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Insect Cells ◽  
Vampire Bat
Sign in / Sign up

Export Citation Format

Share Document