Novel Targets for Platelet Inhibition

Author(s):  
Kathleen Freson ◽  
Chris Van Geet
2016 ◽  
Vol 64 (S 01) ◽  
Author(s):  
A. Böning ◽  
P. Grieshaber ◽  
S. Glass ◽  
P. Roth ◽  
B. Niemann ◽  
...  

1969 ◽  
Vol 22 (02) ◽  
pp. 304-315 ◽  
Author(s):  
E. W Salzman ◽  
T. P Ashford ◽  
D. A Chambers ◽  
Lena L. Neri

SummaryAfter incubation of platelet-rich plasma with labelled adenosine or ADP, platelet incorporation of radioactivity was assessed. Platelets were rapidly separated for counting by filtration through cellulose acetate Millipore. Inulin-H3 served as a plasma marker, and triple isotope techniques permitted simultaneous assessment of the behavior of the adenine and phosphate moieties of ADP without washing of platelets. In other experiments, electron microscopic radioautography was employed to trace the label after platelet incorporation.The results were consistent with previous reports that ADP is dephosphorylated in plasma and is incorporated by platelets only as a dephosphorylated residue, probably adenosine. The label crossed the platelet membrane and entered the platelet, where it was distributed in platelet granules and the agranular cell sap. Concentration within granules occurred to a minor degree.The results support the hypothesis that platelet aggregation by ADP occurs without a persistent bond of ADP to the platelet. Inhibition of aggregation by adenosine probably depends on a metabolic or transport process rather than on competition between adenosine and ADP for platelet binding sites.


1999 ◽  
Vol 19 (03) ◽  
pp. 128-133 ◽  
Author(s):  
B.E. Lewis ◽  
W. P. Jeske ◽  
F. Leya ◽  
Diane Wallis ◽  
M. Bakhos ◽  
...  

SummaryDespite the use of potent anticoagulants such as r-hirudin and argatroban, the morbidity and mortality in heparin-induced thrombocytopenia (HIT) patients remains unacceptable. Data from our in vitro investigations show that thrombin inhibitors do not block platelet activation induced by heparin antibodies and heparin but that GPIIb/IIIa receptor inhibitors do block this process. We have treated four HIT positive patients with a combined therapy of thrombin inhibitor and GPIIb/IIIa receptor inhibitor when treatment with thrombin inhibitor alone failed to alleviate acute thrombosis. Combination therapies included r-hirudin (Refludan®) with tirofiban (Aggrastat®) and argatroban (Novastan®) with abciximab (ReoPro®). A reduced dose of the thrombin inhibitor was used with the standard dose of the anti-platelet drug. In all cases, there was no overt bleeding which required intervention, and all patients exhibited clinical improvement or full recovery. These case studies suggest that treatment of active thrombosis in HIT patients with adjunct GPIIb/IIIa receptor inhibitor therapy may be more effective than thrombin inhibitor treatment alone.


2006 ◽  
Vol 114 (08) ◽  
Author(s):  
M Labeur ◽  
M Paez-Pereda ◽  
M Theodoropoulou ◽  
J Stalla ◽  
B Woelfel ◽  
...  
Keyword(s):  

2010 ◽  
Vol 13 (6) ◽  
pp. E405-E408 ◽  
Author(s):  
David Zimrin ◽  
Johannes Bonatti ◽  
Mark R. Vesely ◽  
Eric J. Lehr

2007 ◽  
Vol 148 (15) ◽  
pp. 697-702 ◽  
Author(s):  
Marianna Murányi ◽  
Zsombor Lacza

It is now known that astrocytes are not merely supporting cells but they also play an important role in neuronal funcions. Astrocytes tightly ensheat neuronal synapses and regulate the excitation of neurons by uptaking neurotransmitters; reglulate the cerebral blood flow, cerebral fluid volume and extracellular concentrations of ions. They also supply fuel in the form of lactate and provide free radical scavangers such as glutathione for active neurons. These facts indicate that impaired function of astrocytes may lead to neuronal dysfunction. After brain injury (stroke, trauma or tumors) astrocytes are swollen and release active molecules such as glutamate or free radicals resulting in neuronal dysfunction. Thus, investigation of the molecular mechanisms of astrocyte function may reveal novel targets for the development of therapeutic tools in neuronal diseases.


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