PLATSAK, a potent antithrombotic and fibrinolytic protein, inhibits arterial and venous thrombosis in a baboon model.
Identifieur interne : 003949 ( Main/Exploration ); précédent : 003948; suivant : 003950PLATSAK, a potent antithrombotic and fibrinolytic protein, inhibits arterial and venous thrombosis in a baboon model.
Auteurs : RBID : pubmed:10828483English descriptors
- KwdEn :
- Animals, Antithrombin III (drug effects), Antithrombin III (metabolism), Blood Platelets (drug effects), Blood Platelets (pathology), Blood Vessel Prosthesis, Diagnostic Imaging, Disease Models, Animal, Evaluation Studies as Topic, Fibrin Fibrinogen Degradation Products (drug effects), Fibrin Fibrinogen Degradation Products (metabolism), Fibrinolytic Agents (pharmacology), Gamma Cameras, Indium Radioisotopes (diagnostic use), Male, Papio, Partial Thromboplastin Time, Peptide Hydrolases (drug effects), Peptide Hydrolases (metabolism), Platelet Adhesiveness (drug effects), Platelet Count (drug effects), Recombinant Fusion Proteins (pharmacology), Thrombosis (drug therapy), Thrombosis (prevention & control), Time Factors.
- MESH :
- chemical , diagnostic use : Indium Radioisotopes.
- chemical , drug effects : Antithrombin III, Fibrin Fibrinogen Degradation Products, Peptide Hydrolases.
- chemical , metabolism : Antithrombin III, Fibrin Fibrinogen Degradation Products, Peptide Hydrolases.
- drug effects : Blood Platelets, Platelet Adhesiveness, Platelet Count.
- drug therapy : Thrombosis.
- pathology : Blood Platelets.
- chemical , pharmacology : Fibrinolytic Agents, Recombinant Fusion Proteins.
- prevention & control : Thrombosis.
- Animals, Blood Vessel Prosthesis, Diagnostic Imaging, Disease Models, Animal, Evaluation Studies as Topic, Gamma Cameras, Male, Papio, Partial Thromboplastin Time, Time Factors.
Abstract
Antiplatelet-antithrombin-staphylokinase (PLATSAK) is a chimeric protein that was recombinantly produced in Escherichia coli cells. The protein was designed to target haemostasis at three different levels. It consists of staphylokinase for activation of fibrinolyis, the Arg-Gly-Asp sequence for the prevention of platelet aggregation, and an antithrombotic peptide for the inhibition of thrombin. The in vivo activity of PLATSAK was evaluated by assessing its effect on platelet deposition in a baboon model of arterial and venous thrombosis. Dacron vascular graft segments and expansion chambers, inserted as extensions into permanent femoral arteriovenous shunts, were used to simulate arterial and venous thrombosis, respectively. PLATSAK (3.68 mg/kg) was administered as a bolus 10 minutes before placement of the thrombogenic devices. Platelet deposition onto the graft surface and in the expansion chamber was imaged in real time with a scintillation camera as the deposition of 111In-labeled platelets. After 2 hours, platelet deposition in the graft segments and expansion chambers was inhibited by 50% and 85%, respectively, when compared to control studies. The activated partial thromboplastin time was lengthened to greater than 120 seconds. Interestingly, the level of fibrinogen degradation products in plasma did not increase after administration of PLATSAK. These results demonstrate that PLATSAK effectively inhibited platelet deposition in both arterial- and venous-type thrombosis in an animal model.
PubMed: 10828483
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">PLATSAK, a potent antithrombotic and fibrinolytic protein, inhibits arterial and venous thrombosis in a baboon model.</title><author><name sortKey="Van Zyl, W B" uniqKey="Van Zyl W">W B van Zyl</name><affiliation wicri:level="1"><nlm:affiliation>Department of Haematology and Cell Biology, University of the Orange Free State, Bloemfontein, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Department of Haematology and Cell Biology, University of the Orange Free State, Bloemfontein</wicri:regionArea></affiliation></author><author><name sortKey="Pretorius, G H" uniqKey="Pretorius G">G H Pretorius</name></author><author><name sortKey="Lamprecht, S" uniqKey="Lamprecht S">S Lamprecht</name></author><author><name sortKey="Roodt, J P" uniqKey="Roodt J">J P Roodt</name></author><author><name sortKey="Kotze, H F" uniqKey="Kotze H">H F Kotzé</name></author></titleStmt><publicationStmt><date when="2000">2000</date><idno type="RBID">pubmed:10828483</idno><idno type="pmid">10828483</idno><idno type="wicri:Area/Main/Corpus">003C72</idno><idno type="wicri:Area/Main/Curation">003C72</idno><idno type="wicri:Area/Main/Exploration">003949</idno></publicationStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antithrombin III (drug effects)</term><term>Antithrombin III (metabolism)</term><term>Blood Platelets (drug effects)</term><term>Blood Platelets (pathology)</term><term>Blood Vessel Prosthesis</term><term>Diagnostic Imaging</term><term>Disease Models, Animal</term><term>Evaluation Studies as Topic</term><term>Fibrin Fibrinogen Degradation Products (drug effects)</term><term>Fibrin Fibrinogen Degradation Products (metabolism)</term><term>Fibrinolytic Agents (pharmacology)</term><term>Gamma Cameras</term><term>Indium Radioisotopes (diagnostic use)</term><term>Male</term><term>Papio</term><term>Partial Thromboplastin Time</term><term>Peptide Hydrolases (drug effects)</term><term>Peptide Hydrolases (metabolism)</term><term>Platelet Adhesiveness (drug effects)</term><term>Platelet Count (drug effects)</term><term>Recombinant Fusion Proteins (pharmacology)</term><term>Thrombosis (drug therapy)</term><term>Thrombosis (prevention & control)</term><term>Time Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Indium Radioisotopes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Antithrombin III</term><term>Fibrin Fibrinogen Degradation Products</term><term>Peptide Hydrolases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antithrombin III</term><term>Fibrin Fibrinogen Degradation Products</term><term>Peptide Hydrolases</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Blood Platelets</term><term>Platelet Adhesiveness</term><term>Platelet Count</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Thrombosis</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Blood Platelets</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Fibrinolytic Agents</term><term>Recombinant Fusion Proteins</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Thrombosis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blood Vessel Prosthesis</term><term>Diagnostic Imaging</term><term>Disease Models, Animal</term><term>Evaluation Studies as Topic</term><term>Gamma Cameras</term><term>Male</term><term>Papio</term><term>Partial Thromboplastin Time</term><term>Time Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Antiplatelet-antithrombin-staphylokinase (PLATSAK) is a chimeric protein that was recombinantly produced in Escherichia coli cells. The protein was designed to target haemostasis at three different levels. It consists of staphylokinase for activation of fibrinolyis, the Arg-Gly-Asp sequence for the prevention of platelet aggregation, and an antithrombotic peptide for the inhibition of thrombin. The in vivo activity of PLATSAK was evaluated by assessing its effect on platelet deposition in a baboon model of arterial and venous thrombosis. Dacron vascular graft segments and expansion chambers, inserted as extensions into permanent femoral arteriovenous shunts, were used to simulate arterial and venous thrombosis, respectively. PLATSAK (3.68 mg/kg) was administered as a bolus 10 minutes before placement of the thrombogenic devices. Platelet deposition onto the graft surface and in the expansion chamber was imaged in real time with a scintillation camera as the deposition of 111In-labeled platelets. After 2 hours, platelet deposition in the graft segments and expansion chambers was inhibited by 50% and 85%, respectively, when compared to control studies. The activated partial thromboplastin time was lengthened to greater than 120 seconds. Interestingly, the level of fibrinogen degradation products in plasma did not increase after administration of PLATSAK. These results demonstrate that PLATSAK effectively inhibited platelet deposition in both arterial- and venous-type thrombosis in an animal model.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">10828483</PMID><DateCreated><Year>2000</Year><Month>08</Month><Day>30</Day></DateCreated><DateCompleted><Year>2000</Year><Month>08</Month><Day>30</Day></DateCompleted><DateRevised><Year>2007</Year><Month>11</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0049-3848</ISSN><JournalIssue CitedMedium="Print"><Volume>98</Volume><Issue>5</Issue><PubDate><Year>2000</Year><Month>Jun</Month><Day>1</Day></PubDate></JournalIssue><Title>Thrombosis research</Title><ISOAbbreviation>Thromb. Res.</ISOAbbreviation></Journal><ArticleTitle>PLATSAK, a potent antithrombotic and fibrinolytic protein, inhibits arterial and venous thrombosis in a baboon model.</ArticleTitle><Pagination><MedlinePgn>435-43</MedlinePgn></Pagination><Abstract><AbstractText>Antiplatelet-antithrombin-staphylokinase (PLATSAK) is a chimeric protein that was recombinantly produced in Escherichia coli cells. The protein was designed to target haemostasis at three different levels. It consists of staphylokinase for activation of fibrinolyis, the Arg-Gly-Asp sequence for the prevention of platelet aggregation, and an antithrombotic peptide for the inhibition of thrombin. The in vivo activity of PLATSAK was evaluated by assessing its effect on platelet deposition in a baboon model of arterial and venous thrombosis. Dacron vascular graft segments and expansion chambers, inserted as extensions into permanent femoral arteriovenous shunts, were used to simulate arterial and venous thrombosis, respectively. PLATSAK (3.68 mg/kg) was administered as a bolus 10 minutes before placement of the thrombogenic devices. Platelet deposition onto the graft surface and in the expansion chamber was imaged in real time with a scintillation camera as the deposition of 111In-labeled platelets. After 2 hours, platelet deposition in the graft segments and expansion chambers was inhibited by 50% and 85%, respectively, when compared to control studies. The activated partial thromboplastin time was lengthened to greater than 120 seconds. Interestingly, the level of fibrinogen degradation products in plasma did not increase after administration of PLATSAK. These results demonstrate that PLATSAK effectively inhibited platelet deposition in both arterial- and venous-type thrombosis in an animal model.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>van Zyl</LastName><ForeName>W B</ForeName><Initials>WB</Initials><Affiliation>Department of Haematology and Cell Biology, University of the Orange Free State, Bloemfontein, South Africa.</Affiliation></Author><Author ValidYN="Y"><LastName>Pretorius</LastName><ForeName>G H</ForeName><Initials>GH</Initials></Author><Author ValidYN="Y"><LastName>Lamprecht</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Roodt</LastName><ForeName>J P</ForeName><Initials>JP</Initials></Author><Author ValidYN="Y"><LastName>Kotzé</LastName><ForeName>H F</ForeName><Initials>HF</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType><PublicationType>Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>UNITED STATES</Country><MedlineTA>Thromb Res</MedlineTA><NlmUniqueID>0326377</NlmUniqueID><ISSNLinking>0049-3848</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Fibrin Fibrinogen Degradation Products</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Fibrinolytic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Indium Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>PLATSAK protein, recombinant</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Recombinant Fusion Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>antithrombin III-protease complex</NameOfSubstance></Chemical><Chemical><RegistryNumber>9000-94-6</RegistryNumber><NameOfSubstance>Antithrombin III</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.-</RegistryNumber><NameOfSubstance>Peptide Hydrolases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Antithrombin III</DescriptorName><QualifierName MajorTopicYN="N">drug effects</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Blood Platelets</DescriptorName><QualifierName MajorTopicYN="N">drug effects</QualifierName><QualifierName MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Blood Vessel Prosthesis</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Diagnostic Imaging</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Evaluation Studies as Topic</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Fibrin Fibrinogen Degradation Products</DescriptorName><QualifierName MajorTopicYN="N">drug effects</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y">Fibrinolytic Agents</DescriptorName><QualifierName MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Gamma Cameras</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Indium Radioisotopes</DescriptorName><QualifierName MajorTopicYN="N">diagnostic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Papio</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Partial Thromboplastin Time</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Peptide Hydrolases</DescriptorName><QualifierName MajorTopicYN="N">drug effects</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Platelet Adhesiveness</DescriptorName><QualifierName MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Platelet Count</DescriptorName><QualifierName MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Recombinant Fusion Proteins</DescriptorName><QualifierName MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Thrombosis</DescriptorName><QualifierName MajorTopicYN="Y">drug therapy</QualifierName><QualifierName MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2000</Year><Month>6</Month><Day>1</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2000</Year><Month>9</Month><Day>2</Day><Hour>11</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2000</Year><Month>6</Month><Day>1</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10828483</ArticleId><ArticleId IdType="pii">S0049-3848(00)00204-8</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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