The removal of protein-bound substances of pathogenetic relevance from blood is of therapeutic interest for drug intoxications, renal and liver failure, and metabolic disorders. Current methods using ...adsorbents are effective but often not specific enough. This work presents an alternative method that enables the dialyzability of albumin-bound toxins from plasma by the use of a high-flux dialyzer (F 60 Fresenius) and an albumin solution circulating on the dialysate side to increase selectively the affinity for albumin-bound toxins. This method resulted in effective removal of unconjugated bilirubin, drugs with a high protein-binding ratio (sulfobromophthalein, theophylline), and a protein-bound toxin (phenol). The additional removal of PBS could extend the applicability of dialysis, for example, to drug intoxications and liver failure or could improve the elimination of protein-bound uremic toxins in chronic renal failure.
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.
The involvement of selenium (Se) in immune response has been increasingly recognized, cell-mediated immunity being principally affected by Se deficiency. Blood Se levels in chronic uraemic patients ...are frequently lower than in controls, and in these patients cellular immunity in generally impaired.
The present study was designed to assess the effects of Se supplementation over 6 consecutive months on immune parameters in haemodialysis (HD) patients from Rostock (Germany) and Chieti (Italy). In both cities, five patients were supplemented with Se (500 micrograms thrice weekly for 3 months, then 200 micrograms thrice weekly for the next 3 months), whereas another five patients received placebo. All Se determinations were performed in a single laboratory.
In both cities, basic plasma Se levels were significantly lower in patients than in their corresponding normal controls. After beginning Se supplementation, plasma Se concentration promptly normalized and levelled off in the normal range throughout the study. Se administration was well tolerated by all patients, and no side-effects attributable to Se toxicity were observed. Although no major change in immunocompetent cells (white blood count, total lymphocyte count, lymphocyte subpopulations) was observed during Se therapy, an improvement in T-cell response to phytohaemoagglutinin (as evaluated in Rostock patients) and a significant progressive increase in delayed-type hypersensitivity (as evaluated in Chieti patients) was observed in supplemented patients. After 6 months of Se therapy, the increase in delayed-type hypersensitivity of supplemented patients proved to be significantly higher when compared to both presupplementation values and to the results found in non-supplemented patients. Three months after suspension of Se supplementation, plasma Se levels and delayed hypersensitivity significantly decreased in Chieti patients, with both parameters returning similar to presupplementation values.
In accordance with previous studies done in non-uraemic subjects, our investigation demonstrates for the first time the immunostimulatory properties of Se in HD patients. Though several problems on Se metabolism in uraemia remain unresolved, in our opinion moderate and safe Se supplementation can be beneficial in chronic uraemic patients.
The neutralization of bacterial endotoxins (ET) is still an unsolved problem in therapeutic medicine. The efficacy of anti-endotoxin antibodies or receptor antagonists and other substances ...interfering with the endotoxin-induced pathomechanisms is dependent on an intact cellular degradation system of the host. However, the phagocytosis function of that system seems to be impaired regularly in patients with intense or long-lasting endotoxemia or septic shock and in patients undergoing hemodialysis. Extracorporeal adsorption of ET might well be an effective support in the anti-ET therapy by lowering the amount of circulating ET and thus relieving the defense system of the body. In this work a new ET-adsorbent based on macroporous cellulosic beads with immobilized polyethylenimine (PEI) was tested for its ET-removal capacity in vitro. A test solution with 100 ng/ml ET from Escherichia coli 055:B5 was recirculated in a system containing the adsorbent beads. Polymyxin B immobilized to the same carrier was used for comparison. PEI as well as polymyxin B showed complete removal of ET from plasma and water as was measured by the Limulus Amebocyte Lysate (LAL) test (Chromogenix). The biocompatibility of the PEI absorber was superior to that of polymyxin B. The results indicate that the PEI absorber is of high efficacy and possibly of interest for the treatment of endotoxemia.
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.
During the past decades, many technological improvements have been made in the construction of extracorporeal liver support systems. Among these achievements, membranes of artificial capillary ...system, used as substrates of hepatocyte growth, aroused our interest in their application for the construction of bioreactors. The present paper studied the comparison of hepatocyte growth and function on six different membranes. Four of them are cellulose based membranes, Cuprophan, Hemophan, Cellulose acetate, and Bioflux; two are synthetic polymer SPAN and Polysulphone. Human hepatoma cell line SMMC-7721, with moderately differentiated hepatocyte-specific functions, was inoculated into the hollow fiber cartridges. These cells were allowed to attach and to grow over these membranes. It was found that there existed differences in hepatocyte immobilization and growth among these membranes. They influenced the growth and functions of hepatoma cells in vitro to some extent. These results show that membrane is an important factor in the construction of capillary membrane bioreactors for artificial liver support.
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