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|Title:||Dermatan Sulfate: A New Concept in Antithrombotic Therapy|
|Authors:||Ryn-McKenna, Van Joanne|
|Department:||Physiology and Pharmacology|
|Abstract:||<p>This study was undertaken to explore the hypothesis<br />that dermatan sulfate, which catalyses thrombin inhibition by<br />heparin cofactor II, prevents thrombosis more effectively than<br />heparin, which catalyses thrombin inhibition by antithrombin<br />III. The rationale for this hypothesis is based upon three<br />general observations. First, higher doses of heparin are<br />required for the treatment of thrombus growth than are<br />required for the prevention of thrombus formation. Second,<br />thrombin bound to fibrin or to vessel wall components in vitro<br />is resistant to inhibition by heparin/antithrombin III.<br />Third, preliminary evidence indicates that the catalysis of<br />thrombin inhibition by antithrombin III-independent inhibitors<br />may be more effective than heparin/antithrombin III. The<br />results of this present study support the above hypothesis and<br />demonstrated that dermatan sulfate, a glycosaminoglycan which<br />catalyses thrombin inhibition by heparin cofactor II,<br />inhibited i) thrombus formation, ii) thrombus growth, and iii)<br />acted synergistically with tPA to enhance thrombolysis, more<br />effectively than heparin. These effects were achieved with minimal detrimental side-effects. These results indicate that<br />dermatan sulfate is an effective antithrombotic agent and<br />support the conclusion that the catalysis of thrombin<br />inhibition by dermatan sulfate/heparin cofactor II provides<br />a more effective pathway for preventing thrombus formation and<br />thrombus growth than the catalysis of thrombin inhibition by<br />heparin/antithrombin III.</p>|
|Appears in Collections:||Open Access Dissertations and Theses|
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