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      Effect of Hemodialysis on Acid Leukocyte-Type Ribonuclease, Alkaline Ribonuclease and Polymorphonuclear Elastase Serum Levels in Patients with End-Stage Renal Disease

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          Abstract

          Background: Low-molecular-weight proteins (LMWPs) are substances of molecular weights 10–35 kDa, which accumulate in plasma of patients with end-stage renal disease (ESRD) due to the abolishment of plasma renal filtration. LMWPs are considered as a separate group of uremic toxins. Aim: The influence of hemodialysis (HD) on the release of some LMWPs from leukocytes was assessed by comparing levels of serum pancreatic-type alkaline RNase and leukocyte-type acid RNase as well aspolymorphonuclear (PMN) elastase. Methods: The mentioned proteins were assayed in 58 ESRD patients on HD prior and after the dialysis session and compared with the results obtained from 36 healthy subjects. The levels of elastase and acid and alkaline RNase were correlated with HD parameters, residual diuresis, predialysis concentrations of serum creatinine, urea and albumin as well as pre- and postdialysis granulocyte count. Results: Changes in PMN elastase produced by the dialysis session positively correlate with changes in acid RNase levels (r = 0.3650; p = 0.0061), while there is no such correlation for alkaline RNase. There is a negative correlation between pre- and postdialysis differences in levels of acid and alkaline RNases (r = –0.3542; p = 0.008), indicating that HD induces liberation of a factor suppressing alkaline RNase. Levels of acid and alkaline RNase negatively correlate with residual diuresis, indicating its significance in control of LMWP accumulation (r = –0.3970; p = 0.0025; r = –0.2596; p = 0.0533, respectively). Conclusions: Dialysis treatment causes an increase in both acid leukocyte-type and alkaline pancreatic-type RNase activity in plasma. Dialysis-related increases in acid RNase activity correlate with the respective changes in PMN elastase, which suggests that leukocyte activation during dialysis contributes to an increase in plasma LMWPs.

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          The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing.

          Neutrophil functions in haemodialysis (HD) patients are altered by uraemia and by HD procedure. We investigated details of the neutrophil dysfunction as its nature and origin is not well understood. This is reflected by conflicting results about neutrophil phagocytosis activity and by scarce data on the neutrophil killing capability in HD patients. Using a flow-cytometric test system we have measured simultaneously phagocytosis and the production of reactive oxygen species (ROS) of neutrophils and in parallel antimicrobial killing of yeast by neutrophils. 117 whole-blood samples of healthy controls and 50 pre- and 50 post-dialysis samples of HD patients, half of them with diabetes mellitus (DM), have been evaluated. We have constructed a model to account for the dependence on the stimulus-to-cell ratio and obtain means for phagocytosis and killing at different incubation times. (i) HD patients have significantly lower neutrophil killing (20%) than healthy controls. (ii) Dialysis improves the killing capability by 10-15%, after dialysis the killing activity remains significantly (10%) below that of the controls. (iii) The percentage of neutrophils, which exhibit phagocytosis and produce ROS, does not differ significantly between HD patients and healthy controls. (iv) Age has no significant influence on phagocytosis and killing. The neutrophil killing capability is reduced in HD patients while the amount of neutrophils that phagocyte and produce ROS remains unchanged. Functional impairment of uraemic neutrophils is therefore mainly a result of their reduced capability to kill microorganisms intracellularly.
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            Spontaneous leukocyte activation and oxygen-free radical generation in end-stage renal disease.

            Oxidative stress and inflammation are common features and major mediators of atherosclerosis in end-stage renal disease (ESRD). Available evidence for oxidative stress in ESRD is indirect and based on accumulation of byproducts of interactions of reactive oxygen species (ROS) with various molecules. Inflammation is a major cause of oxidative stress. To explore the direct link between oxidative stress and inflammation in ESRD, we studied leukocyte integrin expression and ROS production in 18 ESRD patients and 18 controls. ESRD patients showed elevated plasma malondialdehyde (MDA) and increased superoxide and hydrogen peroxide (H(2)O(2)) production by granulocytes and monocytes before dialysis. Hemodialysis resulted in a further rise in plasma MDA and H(2)O(2) production by granulocytes and monocytes. Surface expression of Mac-1 (CD11b and CD18) on granulocytes and monocytes was significantly increased (denoting cell activation) in ESRD patients. Granularity of granulocytes was significantly reduced before dialysis and declined further after dialysis. The magnitude of ROS production by granulocytes and monocytes was directly related with CD11b expression as well as plasma ferritin and parathyroid hormone levels and was inversely related to protein catabolic rate. Thus, this study provides direct evidence of spontaneous leukocyte activation and increased ROS generation (hence the link between oxidative stress and inflammation) in ESRD patients.
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              A 37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome.

              Recent studies have revealed abnormalities in the ribonuclease L pathway in peripheral blood mononuclear cells of patients with the chronic fatigue syndrome. We conducted a blinded study to detect possible differences in the distribution of 2-5A binding proteins in the cells of patients with chronic fatigue syndrome and controls. We studied 57 patients with chronic fatigue syndrome and 53 control subjects (28 healthy subjects and 25 patients with depression or fibromyalgia). A radioactive probe was used to label 2-5A binding proteins in unfractionated peripheral blood mononuclear cell extracts and to compare their distribution in the three groups. A 37 kDa 2-5A binding polypeptide was found in 50 (88%) of the 57 patients with chronic fatigue syndrome compared with 15 (28%) of the 53 controls (P 0.05, compared with 3 (11%) of the 28 healthy subjects and none of the patients with fibromyalgia or depression. The presence of a 37 kDa 2-5A binding protein in extracts of peripheral blood mononuclear cells may distinguish patients with chronic fatigue syndrome from healthy subjects and those suffering from other diseases.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2009
                August 2009
                16 June 2009
                : 112
                : 4
                : c248-c254
                Affiliations
                Departments of aClinical Biochemistry and bNephrology, Collegium Medicum, Jagiellonian University Krakow, Krakow, Poland
                Article
                224791 Nephron Clin Pract 2009;112:c248–c254
                10.1159/000224791
                19546584
                f868c4c2-7329-4a6c-823b-efe8f1d0bd25
                © 2009 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.

                History
                : 06 May 2008
                : 04 December 2008
                Page count
                Figures: 3, Tables: 3, References: 29, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Alkaline ribonuclease,Hemodialysis,PMN elastase,Acid ribonuclease,End-stage renal disease,Residual diuresis,Low-molecular-weight proteins

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