Action of Gold Sodium Thiomalate on Experimental Thrombosis In Vivo

In order to study the effect of gold compounds on the action of thrombin in vivo, experiments were performed to measure platelet survival and the weight of thrombus formation in experimental models of intra-aortic thrombosis by two indwelling aortic catheter methods. We have called these the long an...

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Veröffentlicht in:Journal of pharmaceutical sciences 1991-02, Vol.80 (2), p.113-118
Hauptverfasser: Kean, W.F., Lock, C.J.L., Somers, D., Rischke, J., Nablo, L., Kassam, Yasmin B., Hogan, M.G., Buchanan, W.W., Howard-Lock, H.E.
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container_end_page 118
container_issue 2
container_start_page 113
container_title Journal of pharmaceutical sciences
container_volume 80
creator Kean, W.F.
Lock, C.J.L.
Somers, D.
Rischke, J.
Nablo, L.
Kassam, Yasmin B.
Hogan, M.G.
Buchanan, W.W.
Howard-Lock, H.E.
description In order to study the effect of gold compounds on the action of thrombin in vivo, experiments were performed to measure platelet survival and the weight of thrombus formation in experimental models of intra-aortic thrombosis by two indwelling aortic catheter methods. We have called these the long and short catheter methods. Platelet survival was reduced in all gold-treated and control animals which had indwelling aortic catheters. In the long catheter model, New Zealand White male rabbits were treated with one of the following: gold sodium thiomalate, sterile water, gold thioglucose, gold sodium thiosulfate, disodium thiomalate. Gold sodium thiomalate-treated rabbits had a reduced weight of experimentally induced intra-aortic thrombi compared with animals treated with sterile water or equimolar concentrations of gold thioglucose, gold sodium thiosulfate, or disodium thiomalate. This reduction in thrombus weight in the animals treated with gold sodium thiomalate was not reflected by changes in platelet survival or fibrinolysis. The serum gold levels achieved in these in vivo experiments was in the range of 5.0 × 10-5 to 1.0 × 10-4 M. These values are comparable to levels which can be achieved in human subjects immediately after a gold injection. In the short catheter model, New Zealand White male rabbits were treated with either gold sodium thiomalate, gold thioglucose, disodium thiomalate, or auranofin. Controls were given either water or 0.05% chlorocresol. Water-treated and gold sodium thiomalate-treated animals were also given 51Cr-labeled platelets and 125I-fibrinogen before insertion of the catheter. Gold sodium thiomalate-treated animals had a significant reduction in mean thrombus weight compared with those treated with water, gold thioglucose, disodium thiomalate, auranofin, or chlorocresol. Gold sodium thiomalate-treated animals had a reduced amount of 125I-fibrin accumulation on the vessel wall and thrombus compared with the water-treated group, but no significant reduction in 51Cr-labeled platelet accumulation. The results indicate that pretreatment with gold sodium thiomalate reduces the weight of thrombus in this experimental model of continuous vessel wall injury. The reduction in thrombus weight recorded in these studies was not related to any effect of fibrinolysis or platelet survival.
doi_str_mv 10.1002/jps.2600800205
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We have called these the long and short catheter methods. Platelet survival was reduced in all gold-treated and control animals which had indwelling aortic catheters. In the long catheter model, New Zealand White male rabbits were treated with one of the following: gold sodium thiomalate, sterile water, gold thioglucose, gold sodium thiosulfate, disodium thiomalate. Gold sodium thiomalate-treated rabbits had a reduced weight of experimentally induced intra-aortic thrombi compared with animals treated with sterile water or equimolar concentrations of gold thioglucose, gold sodium thiosulfate, or disodium thiomalate. This reduction in thrombus weight in the animals treated with gold sodium thiomalate was not reflected by changes in platelet survival or fibrinolysis. The serum gold levels achieved in these in vivo experiments was in the range of 5.0 × 10-5 to 1.0 × 10-4 M. These values are comparable to levels which can be achieved in human subjects immediately after a gold injection. In the short catheter model, New Zealand White male rabbits were treated with either gold sodium thiomalate, gold thioglucose, disodium thiomalate, or auranofin. Controls were given either water or 0.05% chlorocresol. Water-treated and gold sodium thiomalate-treated animals were also given 51Cr-labeled platelets and 125I-fibrinogen before insertion of the catheter. Gold sodium thiomalate-treated animals had a significant reduction in mean thrombus weight compared with those treated with water, gold thioglucose, disodium thiomalate, auranofin, or chlorocresol. Gold sodium thiomalate-treated animals had a reduced amount of 125I-fibrin accumulation on the vessel wall and thrombus compared with the water-treated group, but no significant reduction in 51Cr-labeled platelet accumulation. The results indicate that pretreatment with gold sodium thiomalate reduces the weight of thrombus in this experimental model of continuous vessel wall injury. 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Drug treatments ; Platelet Count - drug effects ; Rabbits ; Thrombosis - blood ; Thrombosis - drug therapy</subject><ispartof>Journal of pharmaceutical sciences, 1991-02, Vol.80 (2), p.113-118</ispartof><rights>1991 American Pharmacists Association</rights><rights>Copyright © 1991 Wiley‐Liss, Inc., A Wiley Company</rights><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3725-b0341df24d6470ae9bb55623695822a2a7f25eff1afe6bc2c038103fc11168c43</citedby><cites>FETCH-LOGICAL-c3725-b0341df24d6470ae9bb55623695822a2a7f25eff1afe6bc2c038103fc11168c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjps.2600800205$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjps.2600800205$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=19603640$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1904936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kean, W.F.</creatorcontrib><creatorcontrib>Lock, C.J.L.</creatorcontrib><creatorcontrib>Somers, D.</creatorcontrib><creatorcontrib>Rischke, J.</creatorcontrib><creatorcontrib>Nablo, L.</creatorcontrib><creatorcontrib>Kassam, Yasmin B.</creatorcontrib><creatorcontrib>Hogan, M.G.</creatorcontrib><creatorcontrib>Buchanan, W.W.</creatorcontrib><creatorcontrib>Howard-Lock, H.E.</creatorcontrib><title>Action of Gold Sodium Thiomalate on Experimental Thrombosis In Vivo</title><title>Journal of pharmaceutical sciences</title><addtitle>J. Pharm. Sci</addtitle><description>In order to study the effect of gold compounds on the action of thrombin in vivo, experiments were performed to measure platelet survival and the weight of thrombus formation in experimental models of intra-aortic thrombosis by two indwelling aortic catheter methods. We have called these the long and short catheter methods. Platelet survival was reduced in all gold-treated and control animals which had indwelling aortic catheters. In the long catheter model, New Zealand White male rabbits were treated with one of the following: gold sodium thiomalate, sterile water, gold thioglucose, gold sodium thiosulfate, disodium thiomalate. Gold sodium thiomalate-treated rabbits had a reduced weight of experimentally induced intra-aortic thrombi compared with animals treated with sterile water or equimolar concentrations of gold thioglucose, gold sodium thiosulfate, or disodium thiomalate. This reduction in thrombus weight in the animals treated with gold sodium thiomalate was not reflected by changes in platelet survival or fibrinolysis. The serum gold levels achieved in these in vivo experiments was in the range of 5.0 × 10-5 to 1.0 × 10-4 M. These values are comparable to levels which can be achieved in human subjects immediately after a gold injection. In the short catheter model, New Zealand White male rabbits were treated with either gold sodium thiomalate, gold thioglucose, disodium thiomalate, or auranofin. Controls were given either water or 0.05% chlorocresol. Water-treated and gold sodium thiomalate-treated animals were also given 51Cr-labeled platelets and 125I-fibrinogen before insertion of the catheter. Gold sodium thiomalate-treated animals had a significant reduction in mean thrombus weight compared with those treated with water, gold thioglucose, disodium thiomalate, auranofin, or chlorocresol. Gold sodium thiomalate-treated animals had a reduced amount of 125I-fibrin accumulation on the vessel wall and thrombus compared with the water-treated group, but no significant reduction in 51Cr-labeled platelet accumulation. The results indicate that pretreatment with gold sodium thiomalate reduces the weight of thrombus in this experimental model of continuous vessel wall injury. The reduction in thrombus weight recorded in these studies was not related to any effect of fibrinolysis or platelet survival.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Catheterization - methods</subject><subject>Disease Models, Animal</subject><subject>Fibrinolysis - drug effects</subject><subject>Gold - blood</subject><subject>Gold Sodium Thiomalate - blood</subject><subject>Gold Sodium Thiomalate - therapeutic use</subject><subject>Hemoglobins - drug effects</subject><subject>Leukocyte Count - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microscopy, Electron</subject><subject>Pharmacology. Drug treatments</subject><subject>Platelet Count - drug effects</subject><subject>Rabbits</subject><subject>Thrombosis - blood</subject><subject>Thrombosis - drug therapy</subject><issn>0022-3549</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFP3DAQhS1URLeUK7dKubS3LGM7dpIj2sICWlEkaHu0HGcsTJN4sbMU_j1GWUF7qHoaed73ZsaPkEMKcwrAju7Wcc4kQJUeIHbIjAoGuQRaviOz1GM5F0X9nnyI8Q4AJAixR_ZoDUXN5Ywsjs3o_JB5my1912bXvnWbPru5db7XnR4xS-LJ4xqD63EYdZek4PvGRxez8yH74R78R7JrdRfxYFv3yffTk5vFWb76tjxfHK9yw0sm8gZ4QVvLilYWJWism0YIybisRcWYZrq0TKC1VFuUjWEGeEWBW0MplZUp-D75Ms1dB3-_wTiq3kWDXacH9JuoKpBUlqJO4HwCTfAxBrRqnc7X4UlRUC-pqZSaekstGT5tJ2-aHts3fIop6Z-3uo5Gdzbowbj4ByaBywISV0_cb9fh03-2qour679uyCeviyM-vnp1-KVkyUuhfl4u1dXqjBZf4VS97KomHlPkDw6DisbhYLB1Ac2oWu_-9d1nYtOlmA</recordid><startdate>199102</startdate><enddate>199102</enddate><creator>Kean, W.F.</creator><creator>Lock, C.J.L.</creator><creator>Somers, D.</creator><creator>Rischke, J.</creator><creator>Nablo, L.</creator><creator>Kassam, Yasmin B.</creator><creator>Hogan, M.G.</creator><creator>Buchanan, W.W.</creator><creator>Howard-Lock, H.E.</creator><general>Elsevier Inc</general><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>American Pharmaceutical Association</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>199102</creationdate><title>Action of Gold Sodium Thiomalate on Experimental Thrombosis In Vivo</title><author>Kean, W.F. ; Lock, C.J.L. ; Somers, D. ; Rischke, J. ; Nablo, L. ; Kassam, Yasmin B. ; Hogan, M.G. ; Buchanan, W.W. ; Howard-Lock, H.E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3725-b0341df24d6470ae9bb55623695822a2a7f25eff1afe6bc2c038103fc11168c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood. 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Pharm. Sci</addtitle><date>1991-02</date><risdate>1991</risdate><volume>80</volume><issue>2</issue><spage>113</spage><epage>118</epage><pages>113-118</pages><issn>0022-3549</issn><eissn>1520-6017</eissn><coden>JPMSAE</coden><abstract>In order to study the effect of gold compounds on the action of thrombin in vivo, experiments were performed to measure platelet survival and the weight of thrombus formation in experimental models of intra-aortic thrombosis by two indwelling aortic catheter methods. We have called these the long and short catheter methods. Platelet survival was reduced in all gold-treated and control animals which had indwelling aortic catheters. In the long catheter model, New Zealand White male rabbits were treated with one of the following: gold sodium thiomalate, sterile water, gold thioglucose, gold sodium thiosulfate, disodium thiomalate. Gold sodium thiomalate-treated rabbits had a reduced weight of experimentally induced intra-aortic thrombi compared with animals treated with sterile water or equimolar concentrations of gold thioglucose, gold sodium thiosulfate, or disodium thiomalate. This reduction in thrombus weight in the animals treated with gold sodium thiomalate was not reflected by changes in platelet survival or fibrinolysis. The serum gold levels achieved in these in vivo experiments was in the range of 5.0 × 10-5 to 1.0 × 10-4 M. These values are comparable to levels which can be achieved in human subjects immediately after a gold injection. In the short catheter model, New Zealand White male rabbits were treated with either gold sodium thiomalate, gold thioglucose, disodium thiomalate, or auranofin. Controls were given either water or 0.05% chlorocresol. Water-treated and gold sodium thiomalate-treated animals were also given 51Cr-labeled platelets and 125I-fibrinogen before insertion of the catheter. Gold sodium thiomalate-treated animals had a significant reduction in mean thrombus weight compared with those treated with water, gold thioglucose, disodium thiomalate, auranofin, or chlorocresol. Gold sodium thiomalate-treated animals had a reduced amount of 125I-fibrin accumulation on the vessel wall and thrombus compared with the water-treated group, but no significant reduction in 51Cr-labeled platelet accumulation. The results indicate that pretreatment with gold sodium thiomalate reduces the weight of thrombus in this experimental model of continuous vessel wall injury. The reduction in thrombus weight recorded in these studies was not related to any effect of fibrinolysis or platelet survival.</abstract><cop>Washington</cop><pub>Elsevier Inc</pub><pmid>1904936</pmid><doi>10.1002/jps.2600800205</doi><tpages>6</tpages></addata></record>
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subjects Animals
Biological and medical sciences
Blood. Blood coagulation. Reticuloendothelial system
Catheterization - methods
Disease Models, Animal
Fibrinolysis - drug effects
Gold - blood
Gold Sodium Thiomalate - blood
Gold Sodium Thiomalate - therapeutic use
Hemoglobins - drug effects
Leukocyte Count - drug effects
Male
Medical sciences
Microscopy, Electron
Pharmacology. Drug treatments
Platelet Count - drug effects
Rabbits
Thrombosis - blood
Thrombosis - drug therapy
title Action of Gold Sodium Thiomalate on Experimental Thrombosis In Vivo
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