Bound toxins protein

Contrary to carbon enterosorbents, Enterosgel does not possess an ability for selective removal of albumin-bound ligands regardless of their affinity with the protein carrier - weak (L-tryptophane), medium (sodium caprylate, deoxycholic acid), or strong (indole-3-carboxylic acid and unconjugated bilirubin). It means that if protein-bound toxins are removed by Enterosgel, this occurs simultaneously with adsorption of the carrier protein. 

Sarnatskaya V, Yushko L, Nikolaev A et al (2007) New approaches to the removal of protein-bound toxins from blood plasma of uremic patients. Artif Cells Blood Substit ImmobU Biotechnol 3 287-308... 

Deliganding Carbonic Adsorbents for Simultaneous Removal of Protein-Bound Toxins, Bacterial Toxins and Inflammatory Cytokines... 

Keywords Uremic toxins Protein bound toxins... 

One should also consider that protein-bound toxins, due to their hydrophobicity can easily pass through a lipoprotein cell membrane acting directly on intracellular structures. 

Artificial liver support systems aim at the extracorporeal removal of water soluble and protein-bound toxins (albumin being the preferential binding protein) associated with hepatic failure. Albumin contains reversible binding sites for substances such as fatty acids, hormones, enzymes, dyes, trace metals and drugs [26] and therefore helps elimination by kidneys of substances that are toxic in the unbound state. It should be noticed that the range of substances to be removed is broad and not completely identified. Clinical studies showed that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver. Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile adds, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be benefidal to the dinical course of a patient in liver failure. 

M.S.L. Tijink, M. Wester, G. Glorieux, K. Gerritsen, J. Sun, P.C. Swart, Z. Borneman, M. Wessling, R. Vanholder, J. A. Joles, D. Stamatiahs, Mixed matrix hollow fiber membranes for removal of protein-bound toxins from human plasma. Biomaterials, 34 (32), 7819-7828,... 

Vanholder et al. (2001) reported increases of protein-bound toxins in dialysis patients and their biological impact. Albumin is the principal protein present in blood and is a caniCT for a number of solutes that are poorly soluble in free solution. So-called albumin dialysis is a process in which blood is dialyzed against an albumin solution that itself undergoes purification by another method (such as adsorption). 

The results of microcolumn experiments presented in Fig. 29.9 prove that perfusion through HSGD purifies HSA from a mixture of uremic toxins, which have high, medium and low affinity with albumin (Table 29.1) [11]. The results show that even after 4 h of perfusion the concentration of all three protein-bound uremic toxins remains low, and their clearance is respectively high [10]. 

Sarnatskaya W, Lindup WE, Niwa T et al (2002) Effect of protein-bound uraemic toxins on the thermodynamic characteristics of human albumin. Biochem Pharmacol 63 1287-1296... 

Plasmapheresis This procedure is a further development of blood exchange (M.J. Lepore et at, 1967). The patient s plasma is separated by centrifugation or other appropriate techniques and discarded, so that the protein-bound and fat-soluble toxins circulating in the plasma are removed. This plasma volume is replaced by fresh plasma. At the same time, the separated corpuscular components of the patient s blood are reinfused. Serious complications may arise from the transmission of viral hepatitis and the occurrence of transfusion-related lung disorders (ARDS). Nevertheless, the method involved is simple and has been carried out successfully in individual cases (87, 91) even as plasma exchange with the administration of a high plasma volmne (1.3 1/hr over 8 hours). It has proved to be much more successful when the serum (ca. 31... 

Stange, X, Mitzner, S., Ramlow, W., Gliesche, T., Hickstein, H., Schmidt, R. A new procedure for the removal of protein bound drugs and toxins. ASAIO X. 1993 39 M621-M625... 

Garcia, A. Heinanen, M. Jimenez, L.M. Barbas, C. Direct measurement of homovaniUic, vaniUylmandehc and 5-hydroxyindole acetic acids in urine by capillary electrophoresis. J. Chromatogr., A 2000, 871, 341-350. Vanholder, R. de Smet, R. Lameire, N. Protein bound uremic solutes The forgotten toxins. Kidney Inter., Suppl. 2001, 78, S266-S270. 

However, other cells may respond differently to the toxin. In particular, platelets are able to resist the entry of pertussis toxin, either because they lack surface binding sites for the toxin B oligomer or because they are unable to internalize the bound toxin (Brass et al., 1990). PT-sensitive G proteins expressed in insect Sf9 cells (ovary cells from the insect Spodoptera frugiperda Sf9 cells are employed as an overexpression system for G proteins and other signal transduction components by infection with recombinant baculovirus) are also not modified by the toxin (Mulheron et al., 1994). 

Beside the most commonly used ion separation systems, such as the quadrupole mass analyser, the ion-trap mass analyser and the double-focusing and tri-sector mass analyser, a new system has encountered increasing interest. This system, the time-of-flight (TOP) mass analyser offers fast scanning opportunities coupled with the possibility of detecting ions with high m/z ratios. This provides a useful tool for rapid quality control of sensorial profiles as well as the detection and identification of toxins and proteins or protein-bound substances [42]. 

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