[Research progress of oral anticoagulants in patients with liver diseases].

Patients with liver disease are at an increased risk of both embolism and bleeding. The optimal anticoagulation strategy remains unclear when associated with venous thromboembolic disease. Moreover, currently approved oral anticoagulant drugs undergo metabolism and elimination in the liver with varying degrees of hepatic dysfunction. Thus, impaired liver function may lead to increased risk of bleeding, making anticoagulant therapy more intricate. This article summarizes the risk of bleeding and thrombosis in patients with liver disease, and the clinical research progress of oral anticoagulants in patients with liver disease to facilitate evidence for choosing oral anticoagulants therapy when required.

Accumulation of ofloxacin and tosufloxacin in fluoroquinolone-resistant E coli.

AIM: To make sure whether there is a difference in mechanism existed in the resistant E coli strains accumulated hydrophilic fluoroquinolone ofloxacin and hydrophobic fluoroquinoline tosufloxacin. METHODS: Fluoroquinolone accumulation in bacteria and effect of active efflux were measured by fluorescence method. Analysis of outer membrane proteins was made by SDS-PAGE. E coli strains included JF701 and JF703 that are OmpC- or OmpF-deficient mutants of E coli K-12 respectively, and the susceptible strain Ecs and its in-vitro selected resistant strains R2, R256, and clinical resistant isolates R5, R6. RESULTS: Ecs accumulated ofloxacin almost at the same concentration as JF701, but JF703 did about 1/2 of that lower than JF701. However, four resistant strains accumulated ofloxacin about 5 to 7-fold lower than those susceptible strains. On the other hand, there was no significant difference for the accumulation of tosufloxacin between fluoroquinolone-resistant and -susceptible strains. After addition of proton ionophore DNP for 5 min and 10 min, the accumulation of tosufloxacin slowly decreased in E coli strains, whereas the accumulation of ofloxacin was increased, especially in the resistant strains. A good relevance exists between the accumulation increment of ofloxacin and its MIC for each E coli strain after addition of DNP for 5 min and 10 min (r=0.9623 and 0.8006 respectively). Furthermore, both OmpF and OmpC in Ecs, OmpF-deficiency in R2, R256 and OmpC-deficiency in R5, R6 were observed. CONCLUSION: The accumulation of ofloxacin other than tosufloxacin could be reduced by OmpF-deficiency and active efflux, and the latter may be an important factor in the development of resistance to hydrophilic fluoroquinolone in E coli.

Secondary structure dependent on metal ions of copper,zinc superoxide dismutase investigated by Fourier transform IR spectroscopy.

Copper, zinc superoxide dismutase (Cu2Zn2-SOD) from bovine erythrocyte and its metal ion free derivatives, E2Zn2-SOD, Cu2E2-SOD, and E2E2-SOD (E: empty) were prepared and their secondary structures were investigated by Fourier transform ir spectroscopy. In 20 mM deuterated phosphate buffer (pD 7.5) solution at room temperature, the native Cu2Zn2-SOD contains about 34% beta-strand, 17% beta-turn, and 49% unordered structures, which is similar to the content determined by x-ray crystal structural analysis. The metal ion free derivatives decrease the component of beta-strand and increase the unordered structure component in trend. Especially in the cases of zinc-free derivatives, Cu2E2-SOD and E2E2-SOD, about 24% beta-strand, 20% beta-turn, and 57% unordered structures are obtained. The result indicates that the zinc ion plays an important role in determining the secondary structure of copper,zinc superoxide dismutase.