Alteration of oxidative phosphorylation in uremia.
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Biomedical subjects
Publications and source records attributed to S Koshikawa.
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Dialytic efficiency and biocompatibility of a new modified cellulose membrane (NMC) were examined in vitro and clinically. NMC was obtained by grafting polyethylene-glycol (PEG) chains to the membrane surface of ordinary cellulose (OC), and it was expected that the random movement of PEG chains would prevent blood cells and large plasma proteins from coming into contact with the membrane surface, resulting in improving the biocompatibility and thrombogenicity of the membrane. Surface characteristics of NMC were rendered anionic and hydrophilic, however, the activations of complement and platelet systems were clearly suppressed in NMC. Minimum heparin requirement for hemodialysis was significantly lower with NMC than with OC dialyzer. No significant difference in solute and water removal was observed between the two dialyzers. These results indicate that NMC can provide increased biocompatibility and antithrombogenic effect while retaining the essential dialysis efficiency of OC.
To clarify the roles of endothelin (ET: vasoconstrictor) and platelet activating factor (PAF: vasodilator) in hemodialysis (HD), intradialytic changes in those substances were compared by a crossover study between HD with regenerated cellulose (RC) and polymethylmethacrylate (PMMA) membranes using currently developed radioimmunoassay methods. Hemodialysis patients demonstrated higher plasma ET values than normal controls, and hypertensive HD cases showed the highest levels. Although ET decreased significantly during the initial stage of HD with both membranes, the decreasing rates were greater in the group with intradialytic hypotension than those in the normotensive group. Plasma PAF did not differ among normal controls, hypertensive HD, and normotensive HD patients. Platelet activating factor tended to increase during HD in both hypotensive and normotensive groups; however, the increasing rates were greater in HD with RC than those with PMMA. These results indicate that the decrease in ET may partially contribute to the initiation of HD induced hypotension. Because PAF is an intracellular mediator, and there is an intradialytic increase in PAF with RC membrane, PAF should be regarded as one of the indices of membrane biocompatibility.
The effects of recombinant human erythropoietin (rHuEPO) on endothelial vasoactive substances were evaluated in 19 regular hemodialysis patients. Blood cell counts, plasma endothelin (ET), alpha-human atrial natriuretic peptide (ANP), platelet activating factor (PAF), 6-keto-prostaglandin F1 alpha (PGF1 alpha), and 11-dehydro-thromboxane B2 (TXB2) were evaluated before rHuEPO treatment; at 4, 8, and 12 weeks during treatment; and 5 weeks after the end of treatment. PAF and TXB2 remained unchanged during the study period, PGF1 alpha and ET significantly increased, and ANP decreased along with an improvement in the anemia. Since endothelial vasoactive substances changed significantly during rHuEPO therapy, the correction of anemia with rHuEPO may affect endothelium.
The biocompatibility and thrombogenicity of polyethylene-glycol (PEG)-grafted cellulose hemodialysis (HD) membranes (PEGC) were investigated in cross-over HD of five HD patients with ordinary cellulose (OC). The PEGC significantly suppressed transient leukocyte and thrombocytopenia, and release of C3a, beta-thromboglobulin and platelet factor 4, in corresponding with the quantity of grafted PEG. HD with PEGC resulted in lower granulocyte elastase production, protein and blood cells adsorption on the membrane surface than those with OC. Minimum heparin in HD with PEGC was three times lower than that with OC, with the thrombin-antithrombin III complex elevation lower than that in HD with OC. The results indicate that the grafted PEG effectively suppresses blood and membrane interaction, thus improving biocompatibility and reducing thrombogenicity in clinical HD.
The regional anticoagulating effects of FUT-175 (protease inhibitor), and regional or low dose heparinization (RH or LH) were examined comparatively by randomized controlled protocol on 157 hemodialysis (HD) patients with hemorrhagic complications. Increases in bleeding because of HD were milder in FUT as compared with RH and LH, and the bleeding time after needle removal was significantly shorter in FUT than that in heparin. During HD, the prolongation of celite activated coagulation time (CCT) of the intracorporeal blood was significantly milder in FUT than in heparin and that of blood passing through the dialyzer was increased in FUT compared with LH. FUT showed no prolongation of CCT after HD. These results indicate that FUT is a more useful and safer anticoagulant for HD patients with hemorrhagic complications than any regional anticoagulating method using heparin (RH or LH).
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We have developed a new cellulose membrane in which the active hydroxyl and carboxyl groups of the original cellulose fibers are masked with cationic synthetic polymers. The membrane was shown by in vitro and clinical tests to affect the activation of the complement system very little, and it retains the high dialysis efficiency, good tolerance to steam autoclave sterilization, and economical production cost characteristics of the original cellulose membrane. It thus appears that the new cellulose provides the optimum combination of qualities needed in a hemodialysis membrane.