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      Significance of Platelet-Derived Microparticles and Activated Platelets in Diabetic Nephropathy

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          Abstract

          We measured levels of platelet-derived microparticles (PMP), which have coagulative activity and are produced by platelet activation or physical stimulation, and CD62P/CD63-positive platelets in patients with diabetes mellitus to determine their clinical significance and effects on complications of diabetes including diabetic nephropathy. We also compared these levels before and after administration of the antiplatelet drug cilostazol. Plasma PMP and CD62P/CD63-positive platelet levels were significantly higher in patients with diabetes mellitus than normal controls. CD62P-positive platelet levels were significantly higher in patients with nephropathy than in patients without complications. After administration of cilostazol, PMP and CD62P/CD63-positive platelet levels were significantly decreased. The increases in platelet activity and its related procoagulant activity appear to account in part for the hypercoagulability observed in diabetes mellitus. Our findings suggest that activated platelets might play a role in the development of diabetic nephropathy. Furthermore, antiplatelet therapy with cilostazol for diabetic patients may be useful as antithrombin therapy including antiplatelet therapy, since it suppresses the production of intrinsic coagulants produced by platelet activation.

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          Most cited references 6

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          Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus.

           S Nomura (1995)
          We investigated the association between low-density lipoprotein (LDL), triglycerides, and platelet activation in 18 patients with hypertension age 41-64 years and 18 with diabetes mellitus aged 43-70 years. Platelet P-selectin positivity and the microparticle level (indicators of activation) were both significantly higher in the diabetics than in healthy controls (P-selectin: 28.0% +/- 7.5% vs. 7.3% +/- 4.2%, P < 0.001; microparticles: 1900 +/- 966 vs. 526 +/- 158/10(4) platelets, P < 0.01). In contrast, there was no significant increase of either parameter in the patients with hypertension. Plasma microparticle levels were also significantly greater in the diabetics with high LDL levels than in those with low LDL levels (2375 +/- 949 vs. 1519 +/- 796/10(4) platelets, P < 0.05), and in those with high rather than low triglyceride levels (2188 +/- 845 vs. 1492 +/- 783/10(4) platelets, P < 0.05). However, platelet positivity for P-selectin was not significantly different between these two subgroups. Microparticle and P-selectin levels both showed no significant difference between the hypertensive patients with high and low LDL or triglyceride levels. These results suggest that platelet-derived microparticles may participate in the development or progression of atherosclerosis in patients with diabetes mellitus.
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            Novel structurally distinct family of leucocyte surface glycoproteins including CD9, CD37, CD53 and CD63.

             C Vlcek,  V Horejsí (1991)
            Several of the recently described leucocyte surface (glyco)-proteins with significant amino acid sequence similarity (human CD9, CD37, CD53, CD63, TAPA-1, CO-029 and R2 and several homologues of other species) are distinguished by the polypeptide chain apparently four times crossing the membrane. Although the biological role of none of these molecules is known, their structure, associations with other membrane components and the effects of specific monoclonal antibodies suggest that they may constitute a family of ion channels or other transport molecules.
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              Soluble P-Selectin Is Released from Activated Platelets in vivo during Hemodialysis

              During hemodialysis, platelets are activated across a dialyzer. Soluble P-selectin (sP-selectin) is a form of P-selectin which is a glycoprotein relocated from secretory granules to the surfaces of platelets and endothelial cells after these cells have been physiologically activated. To investigate whether sP-selectin is useful as a marker of platelet activation during hemodialysis, we measured the plasma concentration of sP-selectin by enzyme-linked immunosorbent assay in 6 patients hemodialyzed in our institute using regenerated cellulose (RC) membranes and thereafter polysulfone membranes. Concomitantly, we also measured the plasma concentration of platelet factor 4 and β-thromboglobulin which are released from α-granules of activated platelets. During hemodialysis with RC membranes, the β-thromboglobulin level was significantly increased 15 min (p < 0.05) and the sP-selectin level 15 (p < 0.05) and 180 min (p < 0.05) after initiation of dialysis on the venous side as compared with the arterial side of the hemodialyzer. During hemodialysis with polysulfone membranes, no significant variation in plasma β-thromboglobulin and sP-selectin levels was detected. The platelet factor 4 level increased more significantly across a dialyzer 180 min after initiation of dialysis with RC than with polysulfone membranes (p < 0.01). The changes in plasma platelet factor 4 and β-thromboglobulin levels demonstrated that platelets are more activated during hemodialysis with RC than with polysulfone membranes. The changes in plasma sP-selectin levels during hemodialysis with RC confirm that the release of P-selectin purely from activated platelets was detected by enzyme-linked immunosorbent assay. sP-selectin may be a marker of platelet activation during hemodialysis.
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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                1999
                March 1999
                26 February 1999
                : 81
                : 3
                : 271-277
                Affiliations
                aSecond Department of Internal Medicine, and bFirst Department of Internal Medicine, Kansai Medical University, Osaka, Japan
                Article
                45292 Nephron 1999;81:271–277
                10.1159/000045292
                10050080
                © 1999 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, Tables: 2, References: 50, Pages: 7
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/45292
                Categories
                Original Paper

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