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)

Abciximab-grafted ultrasound sensitive microbubbles were developed for the diagnosis of stroke. The antibody fragment abciximab, which binds to the GP IIb/IIIa and alpha v beta 3 receptors expressed by activated platelets, was chosen because most ischemic strokes are due to arterial thrombi that are mainly composed of platelets. The abciximab antibody fragment was activated by reduction of the disulfide bond for grafting on the microbubbles. The suspension was freeze-dried after the grafting was performed directly on the formed microbubbles. Quantification of the amounts of abciximab present on the surface of the microbubbles was assessed semi-quantitatively by flow cytometry, and quantitatively using radio-labeled abciximab. A protocol for human and rat platelets deposition and fixation was implemented and the expression of the GP IIb/IIIa receptor was validated by immunostaining. The abciximab-grafted microbubbles showed high static and dynamic binding to fixed platelets. Detection by ultrasonography of microbubbles bound on white and red clots gave higher signals compared to Sono Vue microbubbles.
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PMID:Grafting of abciximab to a microbubble-based ultrasound contrast agent for targeting to platelets expressing GP IIb/IIIa - characterization and in vitro testing. 1788 99

Acute ischemic stroke (AIS) is a common cause of morbidity and mortality worldwide. Thrombolytic therapy with tissue plasminogen activator, the only approved treatment for AIS, is received by less than 2% of patients. Moreover, there is a slight increase in hemorrhagic complications with thrombolysis. Therefore, there is a need for newer therapeutic modalities in AIS, which could be used in window periods beyond 3-6 h after stroke onset with fewer hemorrhagic complications. Glycoprotein IIb/IIIa inhibitors (GPI), after their initial success in patients with acute coronary syndromes, promised much in patients with AIS over the past decade or so. However, their exact role in patients with AIS, including the window periods and type of strokes, and the risk of symptomatic or asymptomatic hemorrhage are unclear at the moment. The current review focuses on the literature concerning the use of GPI in AIS and looks at the available evidence regarding their use. Abciximab thought to be safe and effective in initial case series and early trials, has not been shown to improve outcomes in AIS, and is associated with higher rates of hemorrhage. Tirofiban appears to be safe and effective in initial trials and there is a need to conduct further trials to establish its role in AIS.
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PMID:Platelet glycoprotein IIb/IIIa inhibitors in acute ischemic stroke. 1912 33

The Penumbra Stroke System (PSS) was cleared for use in patients with ischemic stroke by the FDA in January 2008. We describe our experience of using this new system in acute large vessel occlusive disease following thrombolysis. Fifteen consecutive patients (mean age 60 years) suffering from acute ischemic stroke were treated with the PSS after intravenous or intra-arterial standard treatment with tissue plasminogen activator (n = 14) or ReoPro (n = 1). All patients presented with TIMI 3 before use of the PSS. Carotid stenting (n = 3) and intracranial balloon angioplasty or stenting (n = 2) were performed if indicated. Neurological evaluation was performed using the NIHSS score and the mRS score. Initial median NIHSS score in 12 patients with occlusions in the anterior circulation was 15; three patients with basilar artery occlusion presented with coma. Median symptom to procedure start time was 151 min. In the anterior circulation, 9 of the 12 target vessels were recanalised successfully (TIMI 2 and 3). The rate of patients with independent clinical outcome (mRS </= 2) was 42%. One patient died 5 days after unsuccessful treatment, one after 28 days and one after 85 days owing to heart attack. Basilar artery occlusions could be recanalised in all cases to TIMI 3. The clinical result after 90 days was mRS 4 in two cases and mRS 5 in one case. Symptomatic haemorrhage did not occur. The PSS can safely be used for recanalisation in patients with acute ischemic stroke due to large vessel occlusion, who have already received thrombolysis treatment. The recanalisation rate was 80%. Symptomatic haemorrhage did not occur. Randomized trials may demonstrate that endovascular mechanical thrombectomy improves patient outcome.
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PMID:Penumbra Stroke System as an "add-on" for the treatment of large vessel occlusive disease following thrombolysis: first results. 1935 Feb 48

About 80% of strokes are ischaemic. Approximately 12% of patients die within 3 months following stroke, and another 20% are institutionalised or become highly dependent. In early 2013, what is the harm-benefit balance of antithrombotic treatments used in the acute phase of ischaemic stroke? To answer this question, we reviewed the available data using the standard Prescrire methodology. Clinical trials of aspirin in the acute phase of ischaemic stroke consist mainly of two randomised trials including a total of 40 541 patients. After 1 to 6 months, 13 deaths or sequelae resulting in dependence are prevented when 1000 patients are treated with aspirin during the acute phase. Aspirin increases the risk of symptomatic intracranial haemorrhage when it is introduced less than 24 hours after treatment with alteplase. Abciximab, an injectable antiplatelet agent, showed no tangible clinical benefit in 5 randomised placebo-controlled trials in a total of 1275 patients. Clopidogrel and prasugrel, two other antiplatelet agents, have not been evaluated in this setting. However, in case of allergy to aspirin, clopidogrel is a useful alternative in other situations associated with a risk of arterial ischaemia. In a randomised trial including 458 patients, cilostazol and aspirin were similarly effective after 3 months of follow-up, but cilostazol caused cardiac arrhythmias. Ticlopidine has too many adverse effects to consider it a useful drug. Anticoagulant therapy during the acute phase of stroke has an unfavourable harm-benefit balance, including in patients with stroke secondary to cardiac embolism. Low-molecular-weight heparin reduces the risk of pulmonary embolism but has no impact on overall mortality. The aim of thrombolysis is to unclog the affected artery. Intravenous alteplase administration is the best-assessed thrombolytic method. Twelve randomised trials have compared intravenous thrombolysis with alteplase versus no thrombolytic therapy in 7012 patients. Among patients treated within 3 hours after stroke onset, 41% survived without sequelae after alteplase administration, versus 32% in the absence of thrombolysis; alteplase had no statistically significant impact on mortality at the end of follow-up. Efficacy appeared to be similar in patients over 80 years old.The harm-benefit balance may also be favourable when thrombolysis is started more than 3 hours after stroke onset, but when it is initiated more than 4.5 hours after stroke onset, it increases mortality. Four randomised trials showed that intra-arterial thrombolysis with urokinase or pro-urokinase had a beneficial effect, versus no thrombolysis, in a total of 356 patients. In a randomised trial including 362 patients, intra-arterial thrombolysis did not have a better harm-benefit balance than intravenous thrombolysis. Among the various physical and mechanical methods used to remove or dissolve clots, the best-evaluated is ultrasound plus intravenous alteplase thrombolysis; initial results with this procedure warrant further clinical trials. Rapid intervention and patient selection are both crucial in optimising the harm-benefit balance of intravenous alteplase thrombolysis. This treatment should only be used when management begins within the first hours following stroke symptom onset, and when there are no risk factors for bleeding, especially intracranial bleeding. For other patients, aspirin is the only antithrombotic drug known to reduce, albeit only slightly, the risk of death and sequelae following ischaemic stroke.
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PMID:Antithrombotic drugs and ischaemic stroke. 2442 42

Neurointerventional surgery offers the potential to deliver remarkable intravascular therapies for various neurovascular diseases and stroke. This approach, however, carries a risk of complications that need to be kept to a minimum. Thromboembolism is one of the most consequential complications of neurointerventional surgery in the treatment of intracranial aneurysms. Both antiplatelet and anticoagulant therapies have shown to reduce the risk of thromboembolism in this setting. In this paper, we review the role of antiplatelet therapy in the endovascular management of intracranial aneurysms. For unruptured aneurysms, the use of antiplatelet agents to pre-medicate patients before and during the procedure appears safe and effective in reducing the thrombotic risk. Abciximab has not been extensively studied, but seems to be safe as a salvage maneuver in the case of thrombus formation even in ruptured aneurysms (when the dome is relatively secure) with low rates of intraprocedure and procedure hemorrhagic complications. Further innovation and research are needed to further reduce thromboembolic risks of aneurysm coiling.
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PMID:The role of antiplatelet therapy in aneurysm coiling. 2461 39


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