Background Thrombocytopenia, a common side effect of Arg-Gly-Asp-mimetic antiplatelet drugs, is associated with drug-dependent antibodies (DDAbs) that recognize conformation-altered integrin α β . Objective To explore the correlation between α β binding epitopes and induction of DDAb binding to conformation-altered α β , we examined whether two purified disintegrins, TMV-2 and TMV-7, with distinct binding motifs have different effects on induction of α β conformational change and platelet aggregation in the presence of AP2, an IgG inhibitory mAb raised against α β . Methods We investigated the possible mechanisms of intrinsic platelet activation of TMV-2 and TMV-7 in the presence of AP2 by examining the signal cascade, tail bleeding time and immune thrombocytopenia in Fc receptor γ-chain IIa (FcγRIIa) transgenic mice. Results TMV-7 has a binding motif that recognizes the α β-propeller domain of α β , unlike that of TMV-2. TMV-7 neither primed the platelets to bind ligand, nor caused a conformational change of α β as identified with the ligand-induced binding site mAb AP5. In contrast to eptifibatide and TMV-2, cotreatment of TMV-7 with AP2 did not induce FcγRIIa-mediated platelet aggregation and the downstream activation cascade. Both TMV-2 and TMV-7 efficaciously prevented occlusive thrombosis in vivo. Notably, both eptifibatide and TMV-2 caused severe thrombocytopenia mediated by FcγRIIa, prolonged tail bleeding time in vivo, and repressed human whole blood coagulation indexes, whereas TMV-7 did not impair hemostatic capacity. Conclusions TMV-7 shows antiplatelet and antithrombotic activities resulting from a mechanism different from that of all other tested α β antagonists, and may offer advantages as a therapeutic agent with a better safety profile.
The transmissive and reflective gamma curve incongruence is a serious issue for single gap TRLCD. ACC (Advanced Capacitor Coupling) technology has been developed to make the reflective gamma curve similar to the transmissive gamma curve. The threshold voltage and slop of reflective gamma curve are well controlled. The cross‐talk issue due to electrical coupling of data line is also solved by a new electrical shielding structure. An improved array process is used to reduce manufacturing cost and increase array throughput. with ACC Tech., the TRLCD can have both simple structure and good transflective optical performances.
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