Gerasdorf Bei Wien, Austria
Gerasdorf Bei Wien, Austria
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Herzog R.,Medical University of Vienna | Herzog R.,Zytoprotec | Bender T.O.,Charité - Medical University of Berlin | Vychytil A.,Medical University of Vienna | And 4 more authors.
Journal of the American Society of Nephrology | Year: 2014

The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. Addition of alanyl-glutamine increased O-GlcNAcylation and partly counteracted its inhibition by DON, also leading to improved cell survival. Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD. © 2014 by the American Society of Nephrology.


Patent
Zytoprotec | Date: 2013-07-03

The present invention relates to a peritoneal dialysis fluid comprising a compound inhibiting glycogen synthase kinase (GSK)-3 activity, in particular (GSK)-3 activity, for use in the prevention of infectious and non-infectious peritoneal complications such as peritonitis, peritoneal membrane injury, damage and failure, barrier dysfunction and mesothelial cell detachment.


The present invention relates to a carbohydrate-based peritoneal dialysis fluid, containing a compound selected from the group consisting of glutamine, preferably L-glutamine; a dipeptide capable of releasing glutamine, L-glutamine in free form, preferably selected from the group consisting of glutaminyl-glycine, glycinyl-glutamine, glutaminyl-alanine, alanyl-glutamine; an oligopeptide consisting of two to seven glutamine, preferably L-glutamine residues; and mixtures thereof. The peritoneal dialysis fluids of the present invention are useful for inhibition of technical failure in a person undergoing peritoneal dialysis treatment.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.19M | Year: 2011

Peritoneal dialysis (PD) and haemodialysis (HD) are life-saving renal replacement therapies for more than 200,000 patients with chronic kidney disease in Europe, and this number increases annually. Although PD and HD have similar mortality rates, PD offers major advantages in terms of quality of life, costs, home-based treatment opportunities and early patient survival. Moreover, PD, rather than HD, offers opportunities for improvements. Nevertheless, only 10% of patients in Europe are treated with PD. Presently, PD research faces a significant shortage in workforce, probably through competition with other specialisations, the absence of a coherent training program and limited trans-European collaboration. The EuTRiPD consortium consists of eight research institutes, an SME and a large private company throughout eight of the EU Member States. Additionally, one multi-national company and three (inter)national organizations that promote education, scholarly excellence and public awareness will be associate partners. Each partner has internationally recognized expertise in PD, ranging from basic to bedside research and from raising awareness on kidney diseases to commercialisation of project results. By providing an inter-disciplinary and intersectoral long lasting training programme in PD research, EuTRiPD will address this need for researchers and clinicians in renal diseases. The scientific goal of EuTRiPD is to advance the current state of the art in PD by carrying out bench to bedside research, focused on the identification of biomarkers and interventions that promote survival and function of the peritoneal membrane. This will finally result in the clinical implementation of new therapeutic approaches. EuTRiPD will deliver twelve skilled ESRs with excellent career opportunities in nephrology and PD research. The unique set up of this training program will equip them with the skills to pursue a career in other disciplines and sectors should they choose to do so.


Patent
Zytoprotec | Date: 2012-12-19

The present invention relates to a peritoneal dialysis fluid comprising a compound inhibiting glycogen synthase kinase (GSK)-3 activity, in particular (GSK)-3 activity, for use in the prevention of infectious and non-infectious peritoneal complications such as peritonitis, peritoneal membrane injury, damage and failure, barrier dysfunction and mesothelial cell detachment.


Trademark
Zytoprotec | Date: 2010-07-06

Pharmaceutical products, namely, dialysis fluids.


Trademark
Zytoprotec | Date: 2010-07-06

Pharmaceutical products, namely, dialysis fluids.


Trademark
Zytoprotec | Date: 2010-07-06

Pharmaceutical products, namely, dialysis fluids.


Trademark
Zytoprotec | Date: 2010-07-06

Pharmaceutical products, namely, dialysis fluids.


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