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      Effect of Polymyxin B-Immobilized Fiber on Blood Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Levels in Acute Respiratory Distress Syndrome Patients

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          Abstract

          Background/Aims: Metalloproteinase (MMP)-9 plays a role in the pathogenesis of acute respiratory distress syndrome (ARDS). Polymyxin B-immobilized fiber (PMX-F) treatment improves circulatory disturbance and oxygenation in ARDS patients. We aimed to assess whether PMX-F treatment alters the blood MMP-9 and tissue inhibitor of MMP (TIMP)-1 levels in ARDS patients. Methods: Twelve ARDS patients who received PMX-F treatment and 20 healthy control volunteers were included in this study. PMX-F was carried out twice at a rate of 100 ml/min for 2 h with a time interval of 24 h. Blood MMP-9 and TIMP-1 levels were measured before and after PMX-F treatment. We monitored blood pressure and the PaO<sub>2</sub>/FiO<sub>2</sub> (PF) ratio before and after PMX-F treatment. Results: The mortality of ARDS patients after PMX-F treatment was 16.7%. Chest X-ray abnormalities were ameliorated in surviving patients after PMX-F treatment. Systolic and diastolic blood pressure increased significantly after PMX-F treatment (p < 0.01). The PF ratio also increased significantly after PMX-F treatment (p < 0.01). Blood MMP-9 and TIMP-1 levels in ARDS patients (126.4 ± 36.4 and 326.5 ± 52.5 ng/ml) were significantly higher than in controls (34.5 ± 12.5 and 160.5 ± 24.5 ng/ml; p < 0.01). PMX-F treatment reduced these levels significantly (the first treatment: MMP-9 85.4 ± 28.6 ng/ml, p < 0.05, TIMP-1 265.8 ± 36.6 ng/ml, p < 0.05; the second treatment: MMP-9 56.5 ± 18.8 ng/ml, p < 0.01, TIMP-1 220.6 ± 30.5 ng/ml, p < 0.01). Conclusion: These data suggest that MMP-9 and TIMP-1 may play a role in the pathogenesis of ARDS and that PMX-F treatment ameliorated increased MMP-9 and TIMP-1 levels in ARDS patients.

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          Most cited references 12

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          Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber.

           T Tani,  H. Aoki,  M Kodama (1994)
          Despite the use of potent antibiotics and intensive supportive care, mortality remains high among septic shock patients, especially those with endotoxemia. To remove endotoxin directly from the blood, a material consisting of polymyxin B that is immobilized on fibers (PMX-F) and that can selectively detoxify endotoxin was developed. In a preliminary clinical study, 16 patients with septic multiple organ failure were treated with direct hemoperfusion using a PMX-F column. This therapy significantly decreased the endotoxin level from 76 pg/mL to 21 pg/mL after 2 hours of direct hemoperfusion. The hyperdynamic state of the cardiac index, which is a characteristic of endotoxic shock, returned to normal levels after treatment. In septic shock patients with a systolic pressure of less than 100 mm Hg, the systolic arterial pressure increased significantly from the pretreatment level. The alleviation of fever caused by this therapy continued until the day after treatment. Of the 16 patients who underwent this therapy, 9 were alive 2 weeks after this therapy and 7 patients were discharged from the hospital alive. Hemoperfusion with PMX may be an effective treatment for sepsis and septic shock.
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            Correlation between plasma endotoxin, plasma cytokines, and plasminogen activator inhibitor-1 activities in septic patients.

             N Koga,  T Okahisa,  M Kodama (2001)
            The objective of this study was to evaluate the relation between the clinical and plasma parameters and the changes in plasma endotoxin activity with 2 hours of endotoxin-adsorbing therapy using polymyxin B (PMX). A total of 88 consecutive patients were admitted for PMX treatment of severe sepsis or septic organ failure. Standard supportive care was continued without alteration during PMX treatment. Endotoxin, tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-10, and plasminogen activator inhibitor-1 (PAI-1) activities and clinical parameters were measured before, immediately after, and the day after PMX treatment. The mean APACHE II and III scores were 24.2 +/- 1.0 and 85.8 +/- 3.0, respectively. The 2-week survival rate was 51.1%. In survivors, TNFalpha, IL-6, IL-10, and PAI-1 activities were significantly decreased during the 2-hour PMX treatment, the following day, or both times. There was no significant change in the parameters, except for TNFalpha, after PMX in nonsurvivors. In the subgroup whose plasma endotoxin decreased more than 30%, IL-6, TNFalpha, and PAI-1 significantly decreased after 2 hours of PMX or the following day (or both), but all four parameters in nonsurvivors showed no significant change. Hence PMX adsorbed plasma endotoxins and contributed to reductions in plasma proinflammatory cytokine levels and to improved clinical parameters during the 2-hour treatment. Changes in these parameters correlated with changes in plasma endotoxin activity in survivors whose plasma endotoxin levels were adequately reduced.
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              Modulation of plasma metalloproteinase-9 concentrations and peripheral blood monocyte mRNA levels in patients with septic shock: effect of fiber-immobilized polymyxin B treatment.

              The authors measured plasma metalloproteinase (MMP)-9 and corresponding monocyte mRNA in 20 patients with septic shock. Plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels were significantly higher in the 10 nonsurviving patients with septic shock than in 10 surviving patients and 25 normal controls. Hemoperfusion using polymyxin B immobilized on fibers (PMX-F), a reportedly effective treatment for septic shock, was studied for effects on MMP-9 in the patients. Increases in plasma MMP-9 concentrations and corresponding monocyte mRNA levels were attenuated significantly by PMX-F treatment in both nonsurviving and surviving patients. These data suggest that plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels may be useful prognostic markers in septic shock, and that PMX-F treatment affects MMP-9.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2004
                May 2004
                09 July 2004
                : 22
                : 3
                : 256-260
                Affiliations
                aDepartment of Medicine, Shinmatsudo Central General Hospital, Chiba; bArtificial Organs Department, Toray Medical Co., Ltd., Tokyo; cDepartment of Pathology, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, and dDepartment of Medicine, Koto Hospital, Tokyo, Japan
                Article
                78494 Blood Purif 2004;22:256–260
                10.1159/000078494
                15148453
                © 2004 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
                Tables: 5, References: 31, Pages: 5
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/78494
                Categories
                Original Paper

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