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      Efficient Adsorption of Tumor Necrosis Factor with an in vitro Set-Up of the Microspheres-Based Detoxification System

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          Abstract

          Background: The Microsperes-Based Detoxification System (MDS) represents a flexible therapeutic option for various diseases, depending on the specificity of the adsorbents applied. A potential application of the MDS is the supportive therapy of sepsis. Methods: Microadsorbents for tumor necrosis factor (TNF) were prepared by immobilization of anti-TNF antibodies on cellulose (1–10 µm) and applied in an experimental set-up using a pool of human plasma (1 liter) spiked with TNF (800 pg/ml) and its soluble receptors (1,000 pg/ml each). Removal of TNF was compared using a plasma filter and the albumin-permeable filter Albuflow. Results: Addition of 4 (2) g of adsorbent to the filtrate circuit reduced TNF concentrations in the pool by 80% (64%). Removal rates did not differ significantly for the different filters. TNF adsorption was not influenced by the presence of excess TNF receptors. Conclusions: Concentrations of mediators can be efficiently modulated with the MDS using small quantities of specific adsorbents.

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          Most cited references 13

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          The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games.

          The members of the tumour necrosis factor (TNF)/tumour necrosis factor receptor (TNFR) superfamily are critically involved in the maintenance of homeostasis of the immune system. The biological functions of this system encompass beneficial and protective effects in inflammation and host defence as well as a crucial role in organogenesis. At the same time, members of this superfamily are responsible for host damaging effects in sepsis, cachexia, and autoimmune diseases. This review summarizes recent progress in the immunobiology of the TNF/TNFR superfamily focusing on results obtained from animal studies using gene targeted mice. The different modes of signalling pathways affecting cell proliferation, survival, differentiation, apoptosis, and immune organ development as well as host defence are reviewed. Molecular and cellular mechanisms that demonstrate a therapeutic potential by targeting individual receptors or ligands for the treatment of chronic inflammatory or autoimmune diseases are discussed.
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            Taming TNF: strategies to restrain this proinflammatory cytokine.

            Recent studies have demonstrated the essential role of tumor necrosis factor alpha (TNF-alpha) in rheumatoid arthritis and Crohn's disease. This article discusses agents known to suppress the formation or activity of TNF-alpha, and summarizes clinical studies using anti-TNF-alpha antibodies.
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              Extracorporeal Therapies in Non-Renal Disease: Treatment of Sepsis and the Peak Concentration Hypothesis

              In the setting of intensive care, patients with acute renal failure often present a clinical picture of the systemic inflammatory response syndrome (SIRS). SIRS can be caused by bacterial stimuli or by non-microbiological stimuli that induce a significant inflammatory response. When this response is exaggerated, the patient experiences multiple organ system failure and a condition of sepsis also defined as a systemic malignant inflammation. This is mostly characterized by an invasion of cytokines and other pro-inflammatory mediators into the systemic circulation where major biological effects take place, including vasopermeabilization, hypotension and shock. At the same time, the monocyte of the septic patient seems to be hyporesponsive to inflammatory stimuli to a certain extent. In this condition, the patient faces a situation of hyperinflammation but at the same time of immunodepression expressing a clinical entity defined as counter anti-inflammatory response syndrome. The general picture of the clinical disorder is therefore better characterized by an immunodysregulation than by a simple pro- or anti-inflammatory disorder. Due to the short half-life of cytokines and other mediators spilled over into the circulation, it is extremely difficult to approach the problem at the right moment with the right pharmacological agent. For these reasons, the peak concentration hypothesis suggests that continuous renal replacement therapies, due to their continuity and unspecific capacity of removal, might be beneficial in cutting the peaks of the concentrations of both pro- and anti-inflammatory mediators, restoring a situation of immunohomeostasis. Thus the patient may benefit from a lesser degree of immunodysregulation and he/she may restore a close-to-normal capacity of response to exogenous stimuli.
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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
                2007
                March 2007
                05 January 2007
                : 25
                : 2
                : 169-174
                Affiliations
                Center for Biomedical Technology, Danube University Krems, Krems, Austria
                Article
                98434 Blood Purif 2007;25:169–174
                10.1159/000098434
                17202809
                © 2007 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: 4, Tables: 1, References: 21, Pages: 6
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/98434
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Blood Purification, Tumor necrosis factor, Sepsis, Adsorption

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