Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The work was to explore the feasibility of protein affinity purification using ligand isolated from phage library. Reteplase was used as the model protein and a humanized semi-synthetic single chain fragment variable phage library as the source of ligand. After four rounds of biopanning, reteplase-specific phage clones were greatly enriched. The scFv gene from the best phage clone was inserted to pET-29a and expressed in E. coli Rosseta. After purification by nickel-affinity and refolding, this scFv protein was proven to recognize reteplase specifically and sensitively in ELISA and dot-blotting. Its binding constant to reteplase was 1.84x10(-8) M, measured by surface plasmon resonance. After immobilized on Sepharose 4B, the scFv was used for the affinity purification of reteplase from milk. It was found that reteplase was highly purified from the starting material. In conclusion, it has been demonstrated that humanized scFv prepared with this approach could be used as a practical affinity ligand for efficient and cost-effective purification of reteplase, as well as other therapeutic proteins.
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PMID:Preparation and characterization of scFv for affinity purification of reteplase. 1650 53

We describe a case of sudden and severe pulseless electrical activity in a 30 year old woman which was managed successfully with reteplase and heparin one day following an anterior cruciate ligament repair. The presentation of a sudden collapse with ECG findings of S1Q3T3, early precordial lead ST depression and partial right bundle branch block were indicative of an acute pulmonary embolus. The cardiopulmonary collapse necessitated rapid treatment in the absence of confirmatory investigations. Reteplase (10 U stat followed by 10 U at 30 minutes) led to a dramatic improvement in the cardiovascular status of the patient. One day following the cardiac arrest the patient was extubated and responding normally. A spiral CT performed later confirmed multiple small embolic defects in the lower pulmonary arteries of both lower lung zones. This case highlights the utility of reteplase in the management of an acute pulmonary embolism and in an emergency, recent surgery is not necessarily a contraindication to its use.
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PMID:Life threatening massive pulmonary embolism treated with reteplase: a case report. 1659 9

There are no reliable data on plasmin or plasminogen activator (PA) activities in blood of patients receiving fibrinolytic treatment. This is due to continuing in vitro action of PA after blood withdrawal. These artefactual changes of PA or plasmin activities have been prevented by arginine stabilization of blood samples of myocardial infarction patients treated with plasminogen activators. Twelve patients with myocardial infarction were treated with reteplase 2 x 10,000,000 units in bolus application; one patient was treated with 100 mg t-PA in continuous infusion. Blood was immediately stabilized with EDTA and arginine. The plasma was analyzed with newly developed assays for plasmin and PA. Maximal plasmin activities in blood were obtained at 40 to 60 minutes reteplase treatment time (0.1-0.6 U/mL = approximately 0.05-0.3 micromol/L plasmin). The 50% clearance rate for plasmatic Pli was greater than 30 minutes. The plasmatic reteplase concentration peaked at approximately 2,000 U/mL after the first bolus infusion and at approximately 1,500-3,500 U/mL after the second bolus infusion. Reteplase was cleared to 50% within less than 30 minutes, also with great inter-individual variation. Arginine stabilization of blood allows reliable determinations of activities of plasmin and PA in blood of patients under fibrinolytic treatment: substantial plasmin activities occur in patients treated by reteplase. Therapeutic thrombolysis might be improved, imitating the physiologic cellular thrombolysis; i.e., polymorphonuclear phagocytes (PMN) that can be activated by singlet oxygen ((1)O(2)). PMN might be superior to PA in selective lysis of pathologic thrombi.
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PMID:Monitoring of plasmin and plasminogen activator activity in blood of patients under fibrinolytic treatment by reteplase. 1670 24

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based) rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.
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PMID:Reteplase: a review of its use in the management of thrombotic occlusive disorders. 1691 28

Tenecteplase, a mutant form of alteplase, possesses pharmacological properties that might favor its use for emergent fibrinolysis of acute pulmonary embolism. Contemporaneous search of the World's literature reveals 14 humans with acute pulmonary embolism treated with tenecteplase. Here, we summarize those cases and report the presentation features, dosing details and outcomes of eight additional patients with acute pulmonary embolism treated with tenecteplase in an academic emergency department. None of our eight patients had a significant hemorrhagic event after tenecteplase, and the outcomes of all eight appear to be acceptable. Taken together, we submit that the present case report and prior case reports are sufficient to comprise a phase I study of the safety and efficacy of tenecteplase to treat acute pulmonary embolism.
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PMID:Tenecteplase to treat pulmonary embolism in the emergency department. 1722 30

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based), rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other fibrin-specific thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.
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PMID:Spotlight on reteplase in thrombotic occlusive disorders. 1726 91

Favorable outcome by hyperacute rt-PA (recombinant tissue-type plasminogen activator) therapy was suggested firstly by randomized controlled trials (RCT) in Japan, and confirmed by the NINDS trial (1995) using alteplase within the initial 3 hours. A phase III clinical trial using open-labeled, single-dose alteplase was carried out in Japan (Japan Alteplase Clinical Trial, J-ACT). The study protocol was almost compatible to that of the NINDS study, except for several modifications including lower dose administration of alteplase (0.6 mg/kg) in the J-ACT than that in the NINDS study (0.9 mg/kg). The clinical backgrounds were almost similar, and frequencies of very favorable outcome at 3-months and symptomatic intracranial hemorrhage were comparable between the studies. The Japanese Government approved the use of intravenous alteplase therapy in October 11, 2005. The Japan Stroke Society published a guideline and gave more than 130 courses for appropriate alteplase therapy immediately after the approval. Clinical results of this therapy were excellent in the initial 21 cases of our hospital. New approaches will open the door to an exciting new era for stroke management. They include MR-based delayed thrombolysis up to 9 hours after stroke onset and ultrasound-enhanced systemic thrombolysis.
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PMID:[Thrombolytic therapy]. 1743 95

Thrombolytic therapy is the only approved therapy for acute ischemic stroke patients. As part of the European approval process, the Safe Implementation of Thrombolysis in Stroke - Monitoring Study (SITS-MOST) was demanded as a Phase IV study to evaluate the safety and efficacy of alteplase in a 3-h time-window. This article summarizes SITS-MOST and compares it with other Phase IV studies. Between 2002 and 2006, 6483 patients were included in 285 centers; median age was 68 years, median National Institutes of Health Stroke Scale (NIHSS) score was 12 and the median time-window was 140 min. The rate of symptomatic intracerebral hemorrhages, defined as parenchymal hemorrhage type 2 combined with a neurological deterioration of at least 4 points on NIHSS, was 1.7% within 24 h after treatment. Symptomatic hemorrhages as defined by the National Institute of Neurological and Communicative Disorders and Stroke criteria occurred in 7.3% of patients. The 3-month mortality was 11.3% and the rate of good clinical outcome (modified Rankin Score 0-2) was 55%. There were no major differences between experienced and inexperienced centers regarding safety or efficacy. The results of SITS-MOST are comparable with the results of the randomized placebo-controlled trials and other Phase IV studies such as standard treatment with Alteplase to Reverse Stroke and Canadian Alteplase for Stroke Effectiveness Study. They confirm that intravenous alteplase is safe and effective in routine clinical practice when used for acute stroke within 3 h of stroke onset, even in centers with little previous experience of thrombolytic therapy but only if the licensing approval criteria are strictly followed. These findings should encourage wider use of thrombolytic therapies for suitable stroke patients treated in stroke centers.
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PMID:Thrombolysis with alteplase for acute ischemic stroke: review of SITS-MOST and other Phase IV studies. 1761 Mar 85

We incorporated diffusion-weighted magnetic resonance imaging (MRI) (DWI) and perfusion-weighted MRI (PWI) to evaluate the efficacy of thrombolysis in experimental embolic stroke using a plasminogen activator, reteplase. Reteplase (rPA) is an unglycosylated plasminogen activator with enhanced fibrinolytic potency. Right internal carotid arteries of 34 rabbits were embolized using aged heterologous thrombi. Baseline DWI and PWI scans 0.5 hours after embolization confirmed successful embolization among 32. Intravenous treatment with rPA (n=11; 1 mg/kg bolus), recombinant tissue plasminogen activator (rt-PA) (n=11; 6 mg/kg bolus over 1 hour), or placebo (n=10) commenced 1 hour after stroke induction. MRIs were performed at 1.75, 3, and 5 hours after embolization. Six hours after embolization, brains were harvested and examined for hemorrhage. Posttreatment areas of diffusion abnormality and perfusion delay were graded using both a semiquantitative scale and percent areas expressed as a ratio of the baseline values. Improved perfusion was seen among the rt-PA, and rPA-treated groups compared with placebo, using a semiquantitative scale (P<.01 rt-PA v controls, P<.05, rPA v controls). DWI scans, however, were not improved with thrombolysis. Cerebral hemorrhage was not increased with thrombolytic treatment, although the incidence of wound site hemorrhage was higher with either rPA or rt-PA. One fatal systemic hemorrhage was observed in each of the thrombolytic-treated groups. Cerebral perfusion was equally improved with either rt-PA or rPA without causing excess cerebral hemorrhage. An advantage of rPA is single-bolus dosing rather than continuous infusion. Use of rPA for stroke treatment should be further explored.
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PMID:Thrombolysis with reteplase, an unglycosylated plasminogen activator variant, in experimental embolic stroke. 1789 78

Rapid reperfusion is the key treatment goal in patients with ST-segment elevation myocardial infarction (STEMI). The American College of Cardiology-American Heart Association (ACC-AHA) 2004 guidelines for the management of STEMI include recommendations for pharmacologic reperfusion with use of fibrinolytic agents. Fibrinolytic agents are the preferred pharmacologic class for the management of STEMI because of their ability to achieve reperfusion and to restore blood flow when administered within 12 hours of symptom onset. Four fibrinolytic agents are approved for the treatment of STEMI in the United States-streptokinase, alteplase, reteplase, and tenecteplase. Several clinical trials have demonstrated the beneficial effects of these therapies in reducing mortality rates in patients with suspected acute myocardial infarction. Alteplase is administered as an intravenous infusion. However, the relatively long half-lives of reteplase and tenecteplase enable bolus administration, which may be more convenient and less time consuming. Reteplase is administered as a double bolus, and dosing does not depend on the patient's weight; tenecteplase is administered as a single bolus, and dosing is weight based. Adherence to the ACC-AHA guidelines, as well as knowledge about the available fibrinolytic agents, is essential for physicians and pharmacists to make informed decisions regarding appropriate pharmacologic reperfusion strategies.
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PMID:Fibrinolytic agents for the management of ST-segment elevation myocardial infarction. 1796 64


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