(2015) Acquired coagulant factor VIII deficiency induced by Bacillus anthracis lethal toxin in mice, Virulence, 6:5, 466-475, DOI: 10.1080/21505594.2015 Keywords: Anthrax, coagulation factor VIII, hemorrhage, lethal toxinMice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. Moreover, LT treatment in mice induced liver damage. In this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. The hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to LT. In agreement with our hypothesis, LT induces cytotoxicity against hepatic cells in vitro. In addition, suppressed expression of coagulation factor VIII (FVIII) in the liver is associated with a prolonged plasma clotting time in LT-treated mice, suggesting a suppressive role of LT in coagulation. Accordingly, we further hypothesized that a loss-of-function approach involving treatments of an anticoagulant should exacerbate LT-induced abnormalities, whereas a gain-offunction approach involving injections of recombinant FVIII to complement the coagulation deficiency should ameliorate the pathogenesis. As expected, a sublethal dose of LT caused mortality in the mice that were non-lethally pretreated with an anticoagulant (warfarin). By contrast, treatments of recombinant FVIII reduced the mortality from a lethal dose of LT in mice. Our results indicated that LT-induced deficiency of FVIII is involved in LT-mediated pathogenesis. Using recombinant FVIII to correct the coagulant defect may enable developing a new strategy to treat anthrax.
Pb(Zr,Ti)O3 films with PbTiO3 interlayers between the film and Pt/Ti/SiO2/Si(100) substrate were fabricated by using a sol–gel spin-on process. Effects of the PbTiO3 interlayer on the phase formation and electrical properties were investigated. A thin PbTiO3 interlayer of about 0.05 µ m is required to effectively enhance the perovskite formation of the Pb(Zr,Ti)O3 films, while a thicker PbTiO3 interlayer limits the perovskite formation. The glass-to-pyrochlore transformation is not significantly influenced by the PbTiO3 interlayer. Doping of La into the PbTiO3 interlayer elevates the perovskite formation temperature. The characteristics related to morphotropic phase boundary of the films are significantly weakened by the PbTiO3 interlayer. The fatigue behavior of the films is generally improved by the PbTiO3 interlayer. It is suggested that atomic diffusion between the Pb(Zr,Ti)O3 film and PbTiO3 interlayer influences the observed electrical properties.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.