Source:http://linkedlifedata.com/resource/pubmed/id/15678117
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-1-28
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pubmed:abstractText |
The binding of platelet glycoprotein (GP) IIb/IIIa to fibrinogen is the final common pathway in platelet aggregation, a process known to play a key role in the pathogenesis of ischemic brain damage. We compared the effects of FK419, a novel nonpeptide GPIIb/IIIa antagonist, with recombinant tissue plasminogen activator (rt-PA) on middle cerebral artery (MCA) patency and ischemic brain damage in a thrombotic stroke model in squirrel monkeys. FK419 not only inhibited in vitro platelet aggregation (IC50: 88 nmol/L), but also showed disaggregatory activity to aggregated platelet (EC50: 286 nmol/L). FK419 dose-dependently reduced the time to first reperfusion and total occlusion time of MCA blood flow when administered immediately after the termination of photoirradiation. FK419 reduced cerebral infarction and ameliorated neurologic deficits with similar dose-dependency. Although rt-PA reduced the time to first reperfusion, total occlusion time, and cerebral infarction, it did not significantly ameliorate neurologic deficits and induced petechial intracerebral hemorrhages. These results indicate: (1) FK419 restored cerebral blood flow after thrombotic occlusion of MCA, (2) FK419 reduced ischemic brain injury by its thrombolytic actions in a non-human primate stroke model, and (3) FK419 has superior antithrombotic efficacy and is safer than rt-PA.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/((S)-2-acetylamino-3-((R)-(1-(3-(pip...,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrinolytic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Aggregation Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Glycoprotein GPIIb-IIIa...,
http://linkedlifedata.com/resource/pubmed/chemical/Propionic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Plasminogen Activator
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0271-678X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
108-18
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15678117-Animals,
pubmed-meshheading:15678117-Blood Platelets,
pubmed-meshheading:15678117-Brain,
pubmed-meshheading:15678117-Brain Ischemia,
pubmed-meshheading:15678117-Cerebral Hemorrhage,
pubmed-meshheading:15678117-Cerebrovascular Circulation,
pubmed-meshheading:15678117-Dose-Response Relationship, Drug,
pubmed-meshheading:15678117-Fibrinolytic Agents,
pubmed-meshheading:15678117-Infarction, Middle Cerebral Artery,
pubmed-meshheading:15678117-Male,
pubmed-meshheading:15678117-Microcirculation,
pubmed-meshheading:15678117-Middle Cerebral Artery,
pubmed-meshheading:15678117-Piperidines,
pubmed-meshheading:15678117-Platelet Aggregation,
pubmed-meshheading:15678117-Platelet Aggregation Inhibitors,
pubmed-meshheading:15678117-Platelet Glycoprotein GPIIb-IIIa Complex,
pubmed-meshheading:15678117-Propionic Acids,
pubmed-meshheading:15678117-Recovery of Function,
pubmed-meshheading:15678117-Reperfusion Injury,
pubmed-meshheading:15678117-Saimiri,
pubmed-meshheading:15678117-Tissue Plasminogen Activator
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pubmed:year |
2005
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pubmed:articleTitle |
FK419, a nonpeptide platelet glycoprotein IIb/IIIa antagonist, ameliorates brain infarction associated with thrombotic focal cerebral ischemia in monkeys: comparison with tissue plasminogen activator.
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pubmed:affiliation |
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co, Ltd, Kashima, Osaka, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study
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