The efficacy and safety of clopidogrel resinate as a novel polymeric salt form of clopidogrel.

A novel polymeric salt of clopidogrel, clopidogrel resinate, was prepared as a anticoagulant drug. To prove the feasibility as a new active substance, clopidogrel resinate was evaluated for its efficacy and safety. In accelerated stability tests, the clopidogrel resinate tablet (Pregrel) showed less brown discoloration and fewer impurities than the clopidogrel bisulfate tablets under open and closed conditions. In toxicity tests, no deaths occurred after a single dose of up to 2000 mg/kg/day and 13-week repeated doses of up to 625 mg/kg/day in rats without abnormal symptoms compared to clopidogrel bisulfate. When clopidogrel resinate was treated onto Caco-2 cell monolayers, clopidogrel, but not the resin, permeated across the cells with a hight permeation coefficient (Papp) of 13.5 +/- 1.13 x 10(-6) cm/sec. Clopidogrel resinate and clopidogrel bisulfate showed similar pharmacokinetics following oral administration to beagle dogs. A single oral administration of clopidogrel resinate dose-dependently inhibited ADP-induced ex vivo aggregation up to 30 mg/kg in rats. In conclusion, clopidogrel resinate was proved to be an efficient and safe polymeric salt as a candidate for a new clopidogrel salt.

Proteases of a Bacillus subtilis clinical isolate facilitate swarming and siderophore-mediated iron uptake via proteolytic cleavage of transferrin.

We isolated a highly serine protease-producing Bacillus subtilis strain (PRY) from a clinical sample and identified it through biochemical testing and ribosomal DNA sequencing. The PRY strain exhibited a robust swarming behavior and was able to digest human transferrin efficiently, concomitantly with the production of catechol-siderophore in the exponential growth phase. The growth of PRY was in proportion to increased iron availability resulting from transferrin destruction. These results suggest that proteases of the B. subtilis PRY strain may play a significant role in the pathogenesis of human infections by facilitating siderophore-mediated iron uptake from transferrin and swarming motility.

Production of catechol-siderophore and utilization of transferrin-bound iron in Bacillus cereus.

In the present study we attempted to ascertain whether Bacillus cereus was able to produce catechol-siderophore(s), and whether it was able to utilize transferrin-bound iron. The growth of B. cereus was stimulated in proportion to the iron-saturation level of the transferrin, and catechol-siderophores were produced in inverse proportion to this level. B. cereus was proved to uptake iron from partially iron-saturated transferrin or holotransferrin, without destroying the transferrin by its proteases. The catechol-siderophores from B. cereus were able to sustain and augment its growth on the transferrin-bound iron. These results indicate that B. cereus has the ability to produce catechol-siderophores, and to utilize transferrin-bound iron as an iron source for growth, via the siderophore-mediated iron-uptake system.