Chemical and Immunological Characterization of Oxidative Nonenzymatic Protein Modifications in Dialysis Fluids

2003 ◽  
Vol 23 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Maria Cristina Ruiz ◽  
Manuel Portero–Otín ◽  
Reinald Pamplona ◽  
Jesús R. Requena ◽  
Joan Prat ◽  
...  

← Background Glucose degradation products (GDP) in dialysis fluids may induce nonenzymatic protein modifications, the chemical nature and biological properties of which should be better defined. ← Aims To characterize nonenzymatic protein modifications present in glucose-based peritoneal dialysis fluids (PDF) and to evaluate the relationship between concentrations of GDP and the derived nonenzymatic modifications, and the potential of PDF for generating these modifications in vitro. ← Methods The presence, distribution, and content of several nonenzymatic protein modifications in PDF were evaluated by immunological methods, by HPLC, and by gas chromatography-mass spectrometry (GC/MS). Peritoneal dialysis fluid-induced oxidative stress in cells was evaluated by flow cytometry. The potential of PDF for generating oxidative and glycoxidative modifications was examined by immunological and cross-linking analyses. ← Results The albumin present in PDF is modified by carboxymethyllysine (CML). GC/MS analyses of PDF proteins confirmed the presence of CML and demonstrated the occurrence of carboxyethyllysine, malondialdehyde lysine, and oxidation-derived semialdehydes. Furthermore, their concentrations in PDF proteins were significantly higher than those in plasma proteins (in all cases, p < 0.02). The concentration of pyrraline, a non-oxidative advanced glycation end-product, increased with dwell time up to 6 hours ( p < 0.03). The PDF induced cellular free-radical production, which was partially inhibited by the Maillard reaction inhibitor aminoguanidine ( p < 0.001). The potential to generate oxidative and glycoxidative modifications demonstrated an inverse relationship with dwell time ( p < 0.05). The PDF was able to induce collagen cross-linking in a close relationship with GDP concentration. ← Conclusions ( 1 ) PDF contains non-oxidative and several oxidative nonenzymatic protein modifications in higher concentrations than plasma. ( 2 ) Peritoneal dialysis fluid induces oxidative stress in vitro, which can be partially inhibited by aminoguanidine. ( 3 ) These properties are directly related to GDP concentration. ( 4 ) Peritoneal dialysis fluid is able to generate glycoxidative and oxidative damage to proteins in vitro in a dwell-time dependent fashion.

1993 ◽  
Vol 3 (8) ◽  
pp. 1508-1515
Author(s):  
T Liberek ◽  
N Topley ◽  
A Jörres ◽  
G A Coles ◽  
G M Gahl ◽  
...  

Solutions were formulated to examine, independently, the roles of osmolality and glucose in the reduction of viability and inhibition of phagocyte function by dextrose-containing peritoneal dialysis fluids. The exposure of neutrophils (polymorphonuclear leukocytes) to test fluids containing > or = 2.7% (wt/vol) glucose resulted in significant cytotoxicity as assessed by the release of lactate dehydrogenase above control values (7.12 +/- 2.65%). At the highest concentration of glucose (4.5%), lactate dehydrogenase release was 15.83 +/- 0.49% (P < 0.05). These effects were directly related to the presence of D-glucose in the test fluids. In contrast, phagocytosis and the release of leukotriene B4 from PMN stimulated with serum-treated zymosan were significantly inhibited in an osmolality-, but not glucose-, dependent manner. The inhibition of tumor necrosis factor alpha and interleukin-6 release from mononuclear leukocytes was inhibited by a combination of osmolality and monosaccharide concentration. Under the same conditions, PMN respiratory burst activation remained unaffected irrespective of glucose concentration or fluid osmolality. These data indicate that, in addition to the low pH of peritoneal dialysis fluid and its high lactate concentration, its glucose content (either directly or as a consequence of the resulting hyperosmolality of the fluid) inhibits cell functional parameters. These findings suggest clinically significant inhibition of host defense mechanisms because, in high-glucose dialysis fluids, osmolality does not reach physiologic values, even during extended intraperitoneal dwell periods.


2007 ◽  
Vol 51 (12) ◽  
pp. 4521-4524 ◽  
Author(s):  
Frances L. Clouse ◽  
Laurie B. Hovde ◽  
John C. Rotschafer

ABSTRACT This study compared the ability of telavancin to the ability of cefazolin and vancomycin to eliminate staphylococci from peritoneal dialysis fluid by using a static in vitro model to simulate the conditions of peritoneal dialysis. The results showed that telavancin exhibited statistically significantly better kill (P < 0.05) against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus.


1983 ◽  
Vol 3 (3) ◽  
pp. 128-129 ◽  
Author(s):  
Carol Loeppky ◽  
Eugene Tarka ◽  
E. Dale Everett

Often dialysis -associated peritonitis is treated before the results of cultures are known with a cephalosporin and an aminoglycoside in combination. Because there may be antagonism between the individual drugs in such combinations, we have investigated this possibility through the use of timed, killing curves in dialysate effluent. We tested various cephalosporins and aminoglycosides alone and in combination at concentrations usually instilled into the peritoneum and determined their activity against one strain each of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The results of these in-vitro studies show no evidence of antagonism but rather suggest an additive effect as evidenced by more rapid killing.


Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1678
Author(s):  
Rebecca Herzog ◽  
Maria Bartosova ◽  
Silvia Tarantino ◽  
Anja Wagner ◽  
Markus Unterwurzacher ◽  
...  

Long-term clinical outcome of peritoneal dialysis (PD) depends on adequate removal of small solutes and water. The peritoneal endothelium represents the key barrier and peritoneal transport dysfunction is associated with vascular changes. Alanyl-glutamine (AlaGln) has been shown to counteract PD-induced deteriorations but the effect on vascular changes has not yet been elucidated. Using multiplexed proteomic and bioinformatic analyses we investigated the molecular mechanisms of vascular pathology in-vitro (primary human umbilical vein endothelial cells, HUVEC) and ex-vivo (arterioles of patients undergoing PD) following exposure to PD-fluid. An overlap of 1813 proteins (40%) of over 3100 proteins was identified in both sample types. PD-fluid treatment significantly altered 378 in endothelial cells and 192 in arterioles. The HUVEC proteome resembles the arteriolar proteome with expected sample specific differences of mainly immune system processes only present in arterioles and extracellular region proteins primarily found in HUVEC. AlaGln-addition to PD-fluid revealed 359 differentially abundant proteins and restored the molecular process landscape altered by PD fluid. This study provides evidence on validity and inherent limitations of studying endothelial pathomechanisms in-vitro compared to vascular ex-vivo findings. AlaGln could reduce PD-associated vasculopathy by reducing endothelial cellular damage, restoring perturbed abundances of pathologically important proteins and enriching protective processes.


2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 365-367 ◽  
Author(s):  
Andrzej Breborowicz ◽  
Malgorzata Pawlaczyk–Kuzlan ◽  
Krzysztof Pawlaczyk ◽  
Ewa Baum ◽  
Paul Tam ◽  
...  

Background Glucose is still used as an osmotic solute in peritoneal dialysis fluids, despite evidence of its local (peritoneal) and systemic toxicities. However a constant search is underway for a new, more biocompatible osmotic solute for peritoneal dialysis fluids. Objective The present study evaluated N-acetylglucosamine (NAG) in a concentration of 220 mmol/ L as an alternative to glucose for the osmotic solute in peritoneal dialysis fluid, during chronic peritoneal dialysis in rats. Methods For 8 weeks, male Wistar rats were infused with glucose-based or NAG-based dialysis fluid. Intraperitoneal inflammation and peritoneal permeability and morphology were evaluated in all rats during the study. Results Repeated intraperitoneal infusion of the NAG-based dialysis fluid resulted in a weaker intra-abdominal inflammatory reaction as compared with the reaction in rats infused with glucose-based dialysis solution. At the end of the study, the concentration of hyaluronan in the peritoneal interstitium obtained from NAG-treated rats was higher than that found in the interstitium taken from animals exposed to dialysis fluid containing glucose. Also, peritoneal permeability to total protein was lower in NAG-treated rats. Conclusion As an alternative to glucose, NAG used for the osmotic solute in peritoneal dialysis solution decreases the intraperitoneal inflammatory reaction induced by the process of peritoneal dialysis and, indirectly (owing to the increased hyaluronan content in the peritoneal interstitium), diminishes peritoneal permeability to protein.


2016 ◽  
Vol 36 (4) ◽  
pp. 367-373 ◽  
Author(s):  
Sarah E. Herlihy ◽  
Hannah E. Starke ◽  
Melisa Lopez-Anton ◽  
Nehemiah Cox ◽  
Katayoon Keyhanian ◽  
...  

Long-term peritoneal dialysis (PD) often results in the development of peritoneal fibrosis. In many other fibrosing diseases, monocytes enter the fibrotic lesion and differentiate into fibroblast-like cells called fibrocytes. We find that peritoneal tissue from short-term PD patients contains few fibrocytes, while fibrocytes are readily observed in the peritoneal membrane of long-term PD patients. The PD fluid Dianeal (Baxter Healthcare Corporation, Deerfield, IL, USA) contains dextrose, a number of electrolytes including sodium chloride, and sodium lactate. We find that PD fluid potentiates human fibrocyte differentiation in vitro and implicates sodium lactate in this potentiation. The plasma protein serum amyloid P (SAP) inhibits fibrocyte differentiation. Peritoneal dialysis fluid and sodium chloride decrease the ability of human SAP to inhibit human fibrocyte differentiation in vitro. Together, these results suggest that PD fluid contributes to the development of peritoneal fibrosis by potentiating fibrocyte differentiation.


2003 ◽  
Vol 64 ◽  
pp. S94-S99 ◽  
Author(s):  
Line Skoufos ◽  
Nicholas Topley ◽  
Laurinda Cooker ◽  
Anne Dawnay ◽  
David J. Millar ◽  
...  

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