Heparins attenuated histone-mediated XXXX in vitro and improved the survival in a @entity35 model of histone-induced @entity881 .

@entity1 @entity8 @entity137 @entity295 @entity326 @entity20806 @entity6950 @entity5642 @entity881 @entity35
BACKGROUND: The beneficial effects of @entity6950 in the treatment of severe @entity295 , @entity326 , and @entity295 -associated disseminated @entity5642 (DIC) have recently been reported. However, the mechanisms underlying the therapeutic benefits of @entity6950 in these conditions have not yet been clearly elucidated. The purpose of this study was to confirm the effect of @entity6950 of neutralizing histone @entity137 . METHODS: @entity35 models of histone H3-induced @entity881 were administered in a low or high dose of unfractionated @entity6950 (UFH), low-molecular-weight @entity6950 (LMWH), or @entity20806 , and the therapeutic effects of each anticoagulant were examined. In another series, the survival of the histone H3-administered animals was evaluated. Furthermore, the effect of each of the aforementioned anticoagulants on cell death induced by histone H3 was examined in cultured vascular endothelial cells and leukocytes. RESULTS: Although UFH, LMWH, and @entity20806 significantly suppressed the histone-induced decrease of the WBC and platelet counts in the animal models of @entity881 , only UFH and LMWH attenuated @entity8 . In addition, the mortality was significantly reduced only by high-dose UFH and LMWH. The in vitro study revealed that both vascular endothelial cell death and leukocyte cell death were significantly attenuated by UFH and LMWH but not by @entity20806 . CONCLUSIONS: The histone-neutralizing effect of @entity6950 may contribute to the beneficial effects of heparins observed in the animal study. The results of the in vitro study further confirmed the above contention and suggested that @entity6950 binds to histones to attenuate the cytotoxic actions of the latter. Since @entity6950 has been demonstrated to protect animals from the organ damage induced by histones and consequently reduce the mortality, administration of @entity6950 could become a treatment of choice for @entity1 suffering from severe @entity295 .
