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Biomedical subjects

J Vienken

Publications and source records attributed to J Vienken.

At least 37 records · Page 2Linked to original sources
PubMed1997

Ex vivo complement protein adsorption on positively and negatively charged cellulose dialyser membranes.

An ex vivo test system was used to measure complement protein C3 and factor B adsorption onto small dialyser modules made from regenerated and modified cellulosic hollow fibre membranes in which positive diethylaminoethyl (DEAE) or negative carboxymethyl (CM) groups were introduced into the cellulose matrix. The extracorporeal system, which included test-dialysers and the dialysis environment, allowed the use of labelled proteins without contaminating the blood donors which were connected in an open-loop fashion to the extracorporeal test system. The modules were removed at selected time points from the extracorporeal system for radioactivity counting. The results were used to evaluate the mechanisms involved in complement reactions to foreign surfaces. The system therefore allowed the analysis of complement protein adsorption occurring in the dialyser modules and its relationship to the complement generation rate in the extracorporeal system to be evaluated. It was possible to demonstrate that significant complement C3 and factor B adsorption occurred in the test modules made of cellulosic membranes. Complement adsorption as a function of the pH and the release reaction of the adsorbed C3 and factor B after membrane blood perfusion were therefore found to be variable according to the cellulosic membrane type and the presence of positive or negative charged groups within the cellulose matrix. The data obtained from the ex vivo model therefore provided additional evidence on the discussion of the mechanisms involved in the increased complement activation by regenerated cellulose and in its attenuation by DEAE- or CM-modified cellulose.

Journal Article↗
PubMed1996

Determination of contact phase activation by the measurement of the activity of supernatant and membrane surface-adsorbed factor XII (FXII): its relevance as a useful parameter for the in vitro assessment of haemodialysis membranes.

We investigated hemodialysis membrane biocompatibility with respect to contact phase activation by determination of FXII-like activity (FXIIA) on the membrane surface and in the supernatant phase, during plasma contact with various hemodialysis membranes using an in vitro incubation test cell. The results were compared to the influence of these membranes on the activation of purified FXII. A time course for the generation of activated FXII using purified FXII solution at physiologic concentrations on two similar negatively charged polymers was performed. The membranes assessed were regenerated cellulose (Cuprophan; Akzo Faser AG, Germany), modified cellulosic (Hemophan; Akzo Faser AG), acrylonitrile-sodium methallyl copolymer-based membrane AN69S (Hospal, France), and SPAN, a new polyacrylonitrile-based copolymer (akzo Nobel AG). The plasma FXIIA at the membranes surface was significantly different between the membranes, while the supernatant phase FXIIA exhibited no significant differences. In contrast, activation of purified FXII in a plasma-free system with respect to supernatant activity indicated significant differences between the materials. A similar finding for the membrane-bound factor XIIA was also observed when purified factor XII was used. The membrane-bound FXIIA values observed in the plasma system containing heparin were significantly greater than in citrated plasma. This demonstrated the strong influence of heparin and the interaction of other plasma components to the membrane surface on the activation of contact phase of coagulation.

Adsorption↗
PubMed1996

Dilemma of membrane biocompatibility and reuse.

Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation, leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.

Anaphylaxis↗
PubMed1996

Comparison of hollow fibre membranes for hepatocyte immobilisation in bioreactors.

Various hollow fibre membranes of polyamide, cellulose and polypropylene were investigated as potential substrata for hepatocyte immobilisation in bioreactors for hybrid liver support systems. Membranes were subjected to a cytocompatibility test in which the attachment and morphology of primary hepatocytes were evaluated. The effect of coating with collagen and fibronectin was also studied. Adequate cell immobilisation was possible on polypropylene and polyamide membranes even without coating. The flattening process of the cells was dependent on the material and the coating. The incorporation of porous polypropylene hollow fibres in hybrid liver cell bioreactors and their specific permeability properties could also offer means for cell oxygenation, metabolite distribution and immuno-isolation purposes.

Animals↗
PubMed1995

In vitro contact phase activation with haemodialysis membranes: role of pharmaceutical agents.

Contact phase activation was investigated in vitro using flat sheet type of haemodialysis membranes, Cuprophan (Akzo, Faser, Germany) and AN69S (Hospal, France), and a negatively charged polyamide Ultipor NR 14225 membrane as a control. The investigation focussed on the determination of factor XII-like activity (FXIIA) as an indicator of contact phase activation in the supernatant phase and at the membrane surface after plasma-membrane contact using an incubation test cell. The findings were compared with the observations from a plasma-free system utilizing purified unactivated factor XII. The plasma FXIIA bound to the membrane surface was significantly different between the membranes, while the supernatant phase FXIIA exhibited no significant differences. In contrast, the plasma-free system exhibited significant differences in the supernatant FXIIA and membrane-bound FXIIA for all the materials used and the magnitude of the activity was significantly greater for negatively charged materials. This finding demonstrated the strong influence of the interaction of other plasma constituents on the membrane surface and as such the binding and subsequent activation of factor XII may be altered possibly due to competitive binding and steric hindrance. On the addition of anticoagulants such as heparin, low-molecular-weight heparin, citrate and hirudin, no significant differences were observed in plasma supernatant phase FXIIA. However, each anticoagulant appears to have a distinct influence on the magnitude of plasma membrane-bound FXIIA. On the addition of aprotinin (a kallikrein inhibitor), no significant differences were observed in the plasma supernatant FXIIA. In contrast, aprotinin appears to significantly reduce membrane-bound FXIIA on Cuprophan and polyamide NR, but significantly increase the magnitude of the membrane-bound FXIIA on AN69S.

Anticoagulants↗
PubMed1995

Biocompatibility of membranes used in the treatment of renal failure.

Haemodialysis membranes with a wide range of solute and hydraulic permeabilities are used clinically. Such membranes are manufactured from either cellulose or synthetic co-polymers and their biocompatibility is commonly characterized by the complement activation and white cell changes observed during their use. The cellobiosic unit may be modified by the partial or total replacement of the hydroxyl groups by diethylaminoethyl (Hemophan), acetate (cellulose acetate), triacetate (cellulose triacetate) or 2,5-acetate (Diaphan). We have undertaken a prospective study in which such renal membranes have been studied in terms of the complement activation and neutropenia produced with the aim of investigating the relationship between modification of the cellobiosic unit and the magnitude of neutropenia and complement activation, and the extent to which membrane base material influences these parameters, by comparing the changes observed in modified cellulose membranes with that for a synthetic membrane (polysulphone). Our findings show that, while the degree of substitution varies between < 1% and total substitution, there is no correlation between the numbers of hydroxyl groups replaced and alteration of complement activation and neutropenia. However, by modification of the cellobiosic unit it is possible to produce a membrane whose biocompatibility is similar to that of a membrane manufactured from a synthetic co-polymer such as polysulphone.

Biocompatible Materials↗
PubMed1995

Membranes for dialysis.

Today, more than 30 different polymers or polymer blends are used as materials for dialysis membranes. They can be categorized following the scheme of a family tree of haemodialysis membranes. The trunk represents membranes from regenerated cellulose, major branches show either synthetically modified cellulose membranes or membranes manufactured from synthetic polymers. As the latter are standardly hydrophobic, small branches elucidate the technique on how these materials have been rendered partially or completely hydrophilic. Complications may arise, when comparing membranes only following their polymer names, such as polysulfone, polyacrylonitrile or polyamide. Due to varying polymer compositions, membranes with the same polymer names may differ in their haemocompatibility, flux properties and adsorption characteristics. Adsorption of proteins like beta 2-microglobulin, fibrinogen and coagulation factors, complement proteins, or hormones like parathormon and erythropoietin are differently adsorbed by dialysis membranes and thus adsorption contributes to the removal characteristics. Of central interest for membrane development and application is the question of how these membranes can be sterilized, as a series of patient adverse reactions has been attributed to the dialyser sterilization procedures. Apart from the cellulosic membranes Cuprophan and Hemophan, the majority of membranes cannot be sterilized by steam, as these materials degrade when exposed to above their class-point temperature. Finally, future aspects of modern membrane development should not neglect the needs of patient populations with specific blood properties, such as diabetics.

Animals↗
PubMed1995

Considerations on developmental aspects of biocompatible dialysis membranes.

Modern strategies in developing new polymers for dialysis membranes aim to improve their blood compatibility. To achieve such a goal, two approaches have been successfully applied: existing cellulosic polymers were modified, either by introducing functional groups through ester or ether bonds, by mixing synthetic polymers with bulk additives, or by using copolymerization techniques. As a detailed example, the first synthetically modified cellulose membrane, Hemophan, was prepared by substituting some hydrogen atoms in the cellulosic glucose unit by diethyl-amino-ethyl groups with the modification having a considerable impact on the membrane's hemocompatibility. It is further known that the hemocompatibility of hydrophobic synthetic membranes is improved by rendering these materials partially hydrophilic. We tested the hypothesis, whether the hemocompatibility of a material, which is hydrophilic per se, such as unmodified cellulose, is changed after the introduction of hydrophobic substituents. For this purpose, the number and nature of substituents have been systematically varied in order to alter surface properties, and these variations have been subsequently related to blood compatibility parameters. As expected, thrombin generation as well as complement- and cell-activation depend on the number and nature of the substituents whereby some of the substituents show a very narrow optimum if their hemocompatibility is related to the degree of substitution. Changes in hemocompatibility can be followed by physical methods, such as surface angle analyses and zeta potential determinations. Data show that alterations in the lipophilic/hydrophilic balance on the polymer surface may explain substituent-related changes in polymer hemocompatibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗
PubMed1994

Membranes for dialysis.

In the submitted review the authors give an account of contemporary problems of membranes for dialysis available at present. Although the authors mention also cellulose based membranes (membranes made from unmodified regenerated cellulose, synthetic modified cellulose membranes produced by chemical transformation of cellobiose), the main attention is paid to polymer membranes--typical synthetic polymers, i.e. polysulphone (PSu), polyacrinon nitrate (PAN), polyamide (PA), ethyl vinyl alcohol polymers (EVAL), polyester mixtures formed by polyacrylonitrile and polyether sulphone (PEPA). The authors describe their adsorption capacity, possibility of sterilization and specific problems of interaction with different drugs. In the conclusion the authors outline demands on the development of modern membranes and their problems in future.

Humans↗
PubMed1994

Bacteria- and endotoxin-free dialysis fluid for use in chronic hemodialysis.

As the quality of water in the dialysis fluid varies considerably, dialysis fluid is contaminated with a high percentage of bacteria and endotoxins. The bacterial populations contained in the dialysis fluid are as heterogeneous as the chemical structure of the endotoxins that result. The latter can pass through the dialysis membrane whereby high-flux membranes permit a larger number of retransportable molecules than low-flux membranes. A central aim toward a future, safe dialysis process should, therefore, be the production of a dialysate that is free of bacteria and endotoxins. As we were able to demonstrate in various examinations, this goal is most likely to be achieved with the aid of sterile filtration using hollow fiber modules of polyamid. To avoid disinfection of the polyamid membrane, as this would only reach bacteria but not endotoxins, the filter was changed after at most 10 h. The achieved dialysis fluid was free of bacteria and endotoxins. We were also able to show that the release of interleukin-1 was reduced. In addition, side-effects, such as a drop in blood pressure, headaches, muscular cramps, and nausea, were reduced.

Bacteria↗
PubMed1994

Cellulose-ester as membrane materials for hemodialysis.

The majority of dialysis membranes are fabricated from regenerated unmodified cellulose. This standard type of cellulosic membrane is frequently under attack because of its alleged lack of biocompatibility. Recent developments, however, have proven that a chemical modification of the reactive surface groups of regenerated cellulose, the hydroxyl-groups, limits the complement-activating potential of these materials and thus improves its blood-compatibility. We extended the idea of modifying cellulose for improved blood-compatibility to a series of different cellulose esters. Special focus was directed towards the question whether a variation of the type of substituent and degree of substitution could influence the blood-compatibility pattern of these materials: the analysis of blood-compatibility profiles showed a direct dependency on the type of substituent and the degree of substitution (DS). As an example, it was found that the DS, necessary for a complete reduction of complement activation, decreases with increasing chain lengths of aliphatic substituents. Optimal degrees of substitution are characteristic of the type of substituents and enable us to tailor materials specifically for optimized blood compatibility.

Biocompatible Materials↗
PubMed1993

Membranes and polymer structures--biocompatibility aspects with respect to production limits.

Plasmapheresis can be performed by centrifugation and by use of membrane technology. With the latter technique we receive a plasma which is absolutely free from platelets. This is why membranes are gaining market shares in this particular field of medical application. Today plasmapheresis membranes are mostly fabricated from synthetic polymers, such as polypropylene (e.g. PLASMAPHAN), polysulfone, polyacrylonitrile, polymethylmethacrylate, polyvinylalcohol and others, the only exception being cellulose acetate. Parameters determining the biocompatibility of plasmapheresis membranes are generation of complement C3a or C5a, hemolysis and possible thrombus formation. These parameters depend on various properties of the membrane polymer: e.g. the nature of the molecular end/side-groups, the distribution of electrical charges on the polymer surface and the different chemical structures and conformation of the polymer. In addition, membrane properties like pore distribution and geometry or the flow characteristics of a particular device-design may trigger cell activation or influence biocompatibility through the adsorption of various plasmacomponents. Most of the polymers which are used today for manufacturing plasmapheresis membranes have not been developed for this purpose. They were originally selected to be used as textile fibers. Further, no present membrane polymer has been specifically developed to achieve high biocompatibility. The membrane profile was designed in such a way that pheresis properties were met rather than optimizing biochemical blood/polymer interactions. One reason for this decision may be that the market volume of plasmapheresis technology is too small in order to justify specific and high-cost developments of polymers for this purpose. Polymer selection to achieve excellent biocompatibility profiles is determined by polymer-availability, costs, membrane-forming processes and environmental aspects related to possible pollution during the manufacturing process. The production of PLASMAPHAN by the unique Accurel-process combines several of these parameters. The main membrane production processes and especially the Accurel-process are described here. The influence of polymer-surface properties, membrane structure and module-design on the biocompatibility of plasmapheresis treatments are discussed and explained by appropriate examples.

Biocompatible Materials↗
PubMed1993

Side effects of hybrid liver support therapy: TNF-alpha liberation in pigs, associated with extracorporeal bioreactors.

During acute liver failure, hybrid liver support therapy could serve as a bridge to liver transplantation. In this desired temporary use, immune competent cell responses, such as the production of cytokines, might be of limiting relevance. We have investigated the Tumor Necrosis Factor-alpha (TNF) liberation in two models using pigs, connected with an extracorporeal bioreactor with homologous hepatocytes: TNF liberation was measured in arterial plasma during a 4 day perfusion time in untreated animals, model (i), and during short term perfusion of hepatectomized pigs in model (ii). Animals four days after catheter implantation in model (i) had TNF values of < 5 pg/ml. After connecting the system without hepatocytes, TNF rose to 9.7 +/- 2 within 120 min and rose further to 32.6 +/- 6 pg/ml within 4 hours after filling the system with the homologous hepatocytes. After 24 hours of continuous perfusion and during four days of perfusion, the TNF levels were lowered to baseline levels. In model (ii), TNF rose to 220 +/- 130 pg/ml within 180 min and decreased to 110 +/- 10 pg/ml within six hours, whereas controls without hepatocytes showed mean levels with a maximum of 120 +/- 20 pg/ml. In both models, there was no correlation between TNF levels and clinical abnormalities such as fever or shock symptoms. There is evidence for an activation of blood cells during experimental extracorporeal hybrid support. No typical side effects were, however, observed. Thus, TNF mediated extracorporeal cell activation does not appear to limit the application of homologous hybrid liver support therapy.

Animals↗