RESUMEN
ABSTRACT: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.
Asunto(s)
Anticoagulantes , Coagulación Sanguínea , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Factor XIIa , Factor XIa , Animales , Factor XIa/antagonistas & inhibidores , Factor XIa/metabolismo , Anticoagulantes/farmacología , Coagulación Sanguínea/efectos de los fármacos , Masculino , Factor XIIa/antagonistas & inhibidores , Factor XIIa/metabolismo , Trombosis de las Arterias Carótidas/prevención & control , Trombosis de las Arterias Carótidas/inducido químicamente , Trombosis de las Arterias Carótidas/tratamiento farmacológico , Ratones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Hemorragia/inducido químicamente , Ratones Endogámicos C57BL , Tiempo de Tromboplastina ParcialRESUMEN
Coherent beam combining (CBC) of two femtosecond third-harmonic (TH) generators is proposed and demonstrated. By applying phase modulation to one of the fundamental laser pulses, the feedback loop effectively eliminates both phase and pointing errors between the two TH femtosecond laser beams. The system delivers 345-nm femtosecond laser pulses with 22-W average power at 1-MHz repetition rate. The average combining efficiency is 91.5% over approximately 1â h of testing. The beam quality of the combined ultraviolet (UV) laser beam is near-diffraction-limited with M2 factors of M X2=1.36, M Y2=1.24, which are similar to those of the individual channels. This scheme exhibits promising potential for increasing high-beam-quality UV laser power.