The antioxidant and non-antioxidant contributions of vitamin E in vitamin E blended ultra-high molecular weight polyethylene for total knee replacement.

Vitamin E (VE) blended ultra-high molecular weight polyethylene (UHMWPE) has been developed in Japan as a material for use in total knee replacement (TKR). Various results have demonstrated that VE blended UHMWPE reduces the incidence of delamination failure and lowers the amount of wear produced during knee simulator testing. It was also found that wear particles from VE blended UHMWPE elicited a reduced biological response compared to conventional UHMWPE. A great deal of research concerning vitamin E (VE) stabilized ultrahigh molecular weight polyethylene (UHMWPE) has focused on VE's effects as an antioxidant and its ability to prevent the oxidative degradation of UHMWPE chains. However, other chemical and mechanical changes have been observed in VE blended UHMWPE that are unrelated to the oxidative protection that VE provides. This paper provides a general review of VE blended UHMWPE, with a particular focus on the non-antioxidant effects of VE. The potential application of VE blended UHMWPE in total hip replacement (THR), along with the differences in loading conditions between the knee and the hip are also discussed.

Osthole prevents anti-Fas antibody-induced hepatitis in mice by affecting the caspase-3-mediated apoptotic pathway.

Fas (Apo-1/CD95) ligand, which is a type II membrane protein, is a major inducer of apoptosis. Osthole is a coumarin derivative present in medicinal plants. The effect of osthole on hepatitis induced by anti-Fas antibody in mice was studied. Pretreatment of mice with osthole (10, 50, and 100 mg/kg, i.p.) prevented the elevation of plasma alanine aminotransferase (ALT) caused by anti-Fas antibody (175 microg/kg, i.v.). Administration of osthole to mice even at a dose of 10 mg/kg significantly inhibited of anti-Fas antibody-induced elevation of plasma ALT. Capase-3 is a cysteine protease, and treatment of mice with anti-Fas antibody caused an elevation of caspase-3 activity at 3.5 and 6 hr. Pretreatment of mice with osthole (100 mg/kg, i.p.) inhibited the elevation of caspase-3 activity caused by anti-Fas antibody. However, the addition of osthole (up to 10(-4)M) to a liver cytosol fraction isolated from mice treated with anti-Fas antibody did not inhibit caspase-3 activity in vitro. Thus, treatment of mice with osthole inhibited caspase-3 activity by an effect upstream of caspase-3 activation. The livers of mice treated with anti-Fas antibody contained apoptotic and dead cells; osthole attenuated the development of this apoptosis and cell death. The present results show that osthole prevented anti-Fas antibody-induced hepatitis by inhibiting the Fas-mediated apoptotic pathway.