PubMed · 4250170
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A A Sharp. 1970. Thrombolysis.. https://doi.org/10.1159/000387618
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A synthetic K vitamin analogue, 2-(2-mercaptothenol)-3-methyl-1,4-naphthoquinone or Cpd 5, was previously found to be a potent inhibitor of cell growth [Nishikawa et al., (1995) J. Biol. Chem. 270, 28304-28310]. The mechanisms of cell growth were hypothesized to include the inactivation of cellular protein tyrosine phosphatases, especially the Cdc25 family [Tamura et al. (2000) Cancer Res. 60, 1317-1325]. In this study, we synthesized PD 49, a new biotin containing Cpd 5 derivative, to search for evidence of direct interaction of these arylating analogues with Cdc25A, Cdc25B, and Cdc25C phosphatases. PD 49 was shown to directly bind to GST-Cdc25A, GST-Cdc25B, their catalytic fragments, and GST-Cdc25C. The binding could be competed with excess glutathione or Cpd 5, and a cysteine-to-serine mutation of the catalytic cysteine abolished binding. This was consistent with an involvement in binding of cysteine in the catalytic domain. This interaction between PD 49 and Cdc25 also occurred in lysates of treated cells. PD 49 also bound to protein phosphatases other than Cdc25. We found that the new analogue also inhibited Hep3B human hepatoma cell growth. This growth inhibition involved ERK1/2 phosphorylation and was inhibited by a MEK antagonist. The results demonstrate a direct interaction and binding between this growth-inhibiting K vitamin derivative with both purified as well as with cellular Cdc25A, Cdc25B, and Cdc25C.
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INTRODUCTION: Transfusion with homologous blood is not without costs for the recipient: An increased risk of postoperative infections must be anticipated, and the risk of transfusion-transmitted viral infections is of growing concern. This has increased the interest for methods which can reduce the need for intraoperative blood transfusion. The goal of this study was to determine if acute normovolemic hemodilution combined with fibrinolytic inhibition and the use of cell saver can reduce the need for homologous blood transfusion in total hip arthroplasty compared to the cellsaver technique alone. MATERIAL AND METHODS: 145 patients undergoing total hip arthroplasty in spinal anesthesia were included in the study. They were all operated by the same surgeon. In group A (N = 64) only the cell saver was used, whereas in group B (N = 81) it was combined with acute normovolemic hemodilution and use of the fibrinolytic inhibitor tranexamic acid. RESULTS: The total blood loss and the need for homologous blood transfusion were significantly smaller in group B than in group A. DISCUSSION: Although the cell saving technique is effective in total hip arthroplasty, this study demonstrates that a further reduction of blood loss and homologous blood transfusion can be achieved by combining the method with acute normovolemic hemodilution and pharmacological inhibition of fibrinolysis.