Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By increasing local cerebral blood flow to ischemic brain tissue in a timely fashion, impending cerebral infarction can be reversed. Aggressive, early intervention is the key to overall neurological improvement of stroke patients. Ancrod, a purified protein fraction of venom from the Malayan pit viper, has been shown to produce rapid and effective defibrinogenation in humans. A current clinical trial with ancrod in patients with acute or progressing nonhemorrhagic ischemic stroke requires an onset to treatment time of no more than 6 hours. Ancillary hospital personnel, physicians and nurses all play important roles in expediting study treatment. Nurses must assess ancrod study patients for potential bleeding problems. Community awareness and education about the warning signs of impending stroke are factors important to insuring early intervention and improving neurological outcome of stroke victims.
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PMID:Experimental ancrod (Arvin) for acute ischemic stroke: nursing implications. 183 48

Clot lysis is desirable in patients with thrombi in arteries and arterioles by a safe rapidly-acting thrombolytic agent. Ancrod cleaves fibrinogen; the resulting circulating ancrod-fibrin stimulates fibrinolysis. Ancrod action and effect were studied in 20 patients with acute developing stroke in a double-blind, placebo-controlled study. Patients were randomly assigned to one of two treatment groups, and received either normal saline or ancrod 0.5 mu/kg in normal saline administered as a constant-rate intravenous infusion over 6 hours. Subsequent doses of ancrod (or saline placebo) were determined daily thereafter for a total treatment period of 7 days. Neither bleeding nor re-thrombosis occurred within the 90 day follow-up period. That ancrod acted rapidly was shown by a significant decrease in functional plasminogen activator inhibitor (PA-I) within 60 minutes, and by significant elevations of fibrin(ogen) degradation products (FDP) and D-dimer within 3 and 4 hours. The biological effect of fibrinolysis in ancrod infused patients was demonstrated by a greater improvement in stroke score when compared to those infused with saline.
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PMID:Ancrod causes rapid thrombolysis in patients with acute stroke. 218 30

Ancrod has been used in Europe for over 15 years for peripheral vascular disease, deep vein thrombosis, and central retinal venous thrombosis, and in patients at risk for thromboembolism. In a double-blind, randomized, placebo-controlled study at University Hospitals in Cincinnati, 20 acute cerebral infarction patients received a series of IV infusions of ancrod (ten) or placebo (ten) for seven days. Early fibrinolysis with a small decrease in fibrinogen was observed, and d-dimers were elevated at four hours, indicating early clot lysis. At three months, patients with moderate to severe strokes (less than 40 on the Scandinavian Stroke Scale) in the ancrod group showed average improvement by a factor of 3 over the placebo group. No bleeding, abnormal laboratory results, or deaths occurred, but ancrod was discontinued in one patient who had seizures. As a result of this study, a double-blind multicenter international clinical trial to further assess the safety and effectiveness of ancrod is being planned.
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PMID:Use of ancrod in acute or progressing ischemic cerebral infarction. 305 31

The venoms from 3 snakes have been shown to induce defibrinogenation: ancrod from the venom of Calloselasma rhodostoma (formerly known as Agkistrodon rhodostoma), batroxobin from the venom of Bothrops atrox moojeni, and crotalase from the venom of Crotalus adamanteus. The purified fractions of ancrod, batroxobin, and crotalase possess coagulant, proteolytic and esterolytic properties, although their primary mechanism of action is a proteolytic effect on circulating fibrinogen. Ancrod cleaves only the A-fibrinopeptides, but not the B-fibrinopeptides, from fibrinogen; this contrasts with thrombin, batroxobin and crotalase, which cleave both fibrinopeptides A and B. Within minutes of administration of ancrod or batroxobin, there is a significant reduction in plasma fibrinogen levels, and these remain exceedingly low with repeated administration (once or twice daily). The rapid fall in plasma fibrinogen levels is accompanied by a slightly delayed but marked rise in the level of fibrinogen-fibrin degradation products. Plasminogen levels are decreased and blood viscosity is reduced, but formed elements in the circulating blood remain unaltered. Ancrod and batroxobin have been investigated in patients with stroke, deep-vein thrombosis, myocardial infarction, peripheral arterial thrombosis, priapism, and sickle-cell crisis; crotalase has not been administered to humans. However, results have been difficult to interpret, and additional well designed trials are needed to better define the optimum role of ancrod and batroxobin in the management of these conditions. Overall, treatment is well tolerated and serious adverse events are infrequent. In the coagulation laboratory, ancrod, batroxobin and crotalase may be used as reagents to perform coagulation studies on specimens of blood that contain heparin. These venom fractions can be substituted for thrombin in performing the thrombin time and in removing fibrinogen from plasma for accurate determination of fibrinogen-fibrin degradation products.
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PMID:Defibrinogenating enzymes. 936 Aug 49

Ancrod converts fibrinogen into soluble fibrin products, resulting in a decrease in plasma fibrinogen and blood viscosity, and also induces the release of endogenous tissue-type plasminogen activator from the vessel wall. These activities suggest that treating patients with acute ischaemic stroke with ancrod might result in improved cerebral blood flow and patient outcome. Two large randomised placebo-controlled studies have evaluated treatment with ancrod in patients with acute ischaemic stroke. In the first, patients were treated within 6 hours of symptom onset: this was not successful in quickly lowering fibrinogen levels to the target range (0.7 to 1.0 g/L) and the results were inconclusive. However, a post hoc analysis suggested that treatment with ancrod was effective in patients whose fibrinogen level was reduced to less than 1.3 g/L within 6 hours of starting treatment. A second larger study is still in progress, but preliminary results in patients treated within 3 hours of onset of ischaemic stroke are available and indicate that the target fibrinogen level of less than 1 g/L within 6 hours of instituting treatment is being achieved in most patients.
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PMID:Ancrod in the treatment of acute ischaemic stroke. 936 Aug 57

The therapeutic window for efficient post-treatment of focal cerebral ischaemia with the fibrinogen lowering agent ancrod was studied by magnetic resonance imaging (MRI) in spontaneously hypertensive rats (SHR). Ancrod or vehicle solution (0.9% NaCl) were i.v. infused (0.12 IU/kg per min) via implanted mini pumps starting 0.5, 1.5, 3 or 6 h after permanent proximal middle cerebral artery occlusion and lasting until brain mapping by multislice T2-weighted magnetic resonance imaging in vivo 24 h after middle cerebral artery occlusion. Plasma fibrinogen concentrations were measured before middle cerebral artery occlusion, before pump implantation and after magnetic resonance imaging. Total brain lesion volumes as determined by magnetic resonance imaging 24 h after middle cerebral artery occlusion were 131 +/- 36 (188 +/- 28)*, 151 +/- 39 (194 +/- 39)*, 147 +/- 44 (207 +/- 33)* and 209 +/- 60 (214 +/- 42) mm3 in rats with 0.5, 1.5, 3 and 6 h, respectively, delay of ancrod treatment (means +/- S.D., 8-11 animals/group, corresponding control groups in parentheses, *P < 0.05). Continuous i.v. ancrod infusions reduced plasma fibrinogen levels significantly (P < 0.05) in all ancrod-treated groups as compared to vehicle-treated controls until the end of the experiments 24 h after middle cerebral artery occlusion. In conclusion, significant cerebroprotection was achieved even when the onset of ancrod therapy for lowering of the plasma fibrinogen level was delayed for up to 3 h. To the best of our knowledge no drug efficacy has been reported so far with a therapeutic window of 3 h after permanent middle cerebral artery occlusion in spontaneously hypertensive rats suggesting that ancrod may provide an efficient therapy of acute human stroke.
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PMID:MRI study on delayed ancrod therapy of focal cerebral ischaemia in rats. 938 48

The development of promising acute stroke treatments is the fruit of the growing appreciation for the complex biochemical processes within neuronal tissue that commence immediately after the onset of ischemia. These biochemical cascades can be modified either by direct pharmacologic mitigation or by rapid restoration of perfusion and oxygenation. With both interventions, the ischemic tissue can remain viable and regain neurologic function rather than progress to infarction. Today the two major pharmacologic approaches to stroke therapy are neuroprotectants and thrombolytics. Neuroprotectants enable neuronal tissues to tolerate periods of minimal perfusion better, whereas thrombolytics facilitate reperfusion by disrupting the fresh thrombus. Important classes of neuroprotectants include calcium channel antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists, benzothiazoles, and free radical scavengers. Pro-urokinase is a potentially important investigational thrombolytic. Ancrod, a defibrinogenating agent, is also currently being evaluated in acute stroke.
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PMID:The stroke pharmacopeia: promising experimental therapies. 961 94

Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of acute ischemic stroke. Treatment with ancrod leads to fibrinogen depletion. The present study investigated the mechanisms leading to the reduction of plasma fibrinogen concentration. Twelve healthy volunteers received an intravenous infusion of 0.17 U/kg body weight of ancrod for 6 hours. Blood samples were drawn and analyzed before and at various time points until 72 hours after start of infusion. Ancrod releases fibrinopeptide A from fibrinogen, leading to the formation of desAA-fibrin monomer. In addition, a considerable proportion of desA-profibrin is formed. Production of desA-profibrin is highest at low concentrations of ancrod, whereas desA-profibrin is rapidly converted to desAA-fibrin at higher concentrations of ancrod. Both desA-profibrin and desAA-fibrin monomers form fibrin complexes. A certain proportion of complexes carries exposed fibrin polymerization sites E(A), indicating that the terminal component of the protofibril is a desAA-fibrin monomer unit. Soluble fibrin complexes potentiate tissue-type plasminogen activator-induced plasminogen activation. Significant amounts of plasmin are formed when soluble fibrin in plasma reaches a threshold concentration, leading to the proteolytic degradation of fibrinogen and fibrin. In the present setting, high concentrations of soluble fibrin are detected after 1 hour of ancrod infusion, whereas a rise in fibrinogen and fibrin degradation products, and plasmin-alpha(2)-plasmin inhibitor complex levels is first detected after 2 hours of ancrod infusion. Ancrod treatment also results in the appearance of cross-inked fibrin degradation product D-dimer in plasma. (Blood. 2000;96:2793-2802)
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PMID:Analysis of fibrin formation and proteolysis during intravenous administration of ancrod. 1102 13

Both anticoagulants and antiplatelet agents have been advocated, used and studied for the treatment of acute ischemic stroke. Randomized trials of unfractionated heparin, low-molecular-weight heparin and heparinoids have failed to show an overall benefit to these agents largely because the benefits in reducing thromboembolic events are offset by the increased risk of bleeding complications. The International Stroke Trial, the Trial of ORG 10172 Acute Stroke Treatment and studies of fraxaripine all failed to show an overall benefit to anticoagulation in the patients studied. Aspirin has been shown to offer a modest benefit when studied in patients treated within 48 h of stroke onset. Ancrod is an antithrombotic agent that acts by reducing circulating fibrinogen levels. Patients treated within 3 h of stroke symptom onset had a better functional outcome at 90 days compared to placebo-treated patients with both the benefits and the risk of intracerebral bleeding related to the fibrinogen lowering achieved. Abciximab is a blocker of the platelet GPIIb/IIIa receptor. A dose finding safety study suggests that in doses up to that typically given in patients with acute coronary occlusion syndromes, there is no increased risk of symptomatic intracerebral bleeding and suggestions of potential benefits on neurological outcome.
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PMID:Antithrombotic therapy in the acute phase: new approaches. 1124

Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of ischemic stroke. The therapeutic effect is ascribed to a lowering of plasma fibrinogen. Thirty-two healthy volunteers received subcutaneous ancrod at doses of 1.0, 1.5 and 2.0 IU/kg body weight or placebo. Blood samples were drawn before the injection and at various time points until 96 h after the injection. Ancrod leads to the formation of desAA-fibrin, which serves as cofactor in tissue plasminogen activator activity (tPA)-induced plasminogen activation. Unchanged concentrations of prothrombin fragment F1.2 and thrombin-antithrombin complex (TAT) indicate that fibrin formation occurs independent of thrombin. Plasmin generation is independent of an increase in tPA activity or changes in plasminogen activator inhibitor-1 (PAI-1) concentration in plasma. Subcutaneous injection of ancrod leads to a generalized fibrino(geno)lytic response caused solely by providing tPA with soluble fibrin as its cofactor in plasminogen activation. Maximal plasmin activity is present 12 h after subcutaneous injection.
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PMID:Plasminogen activation without changes in tPA and PAI-1 in response to subcutaneous administration of ancrod. 1175 54


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