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Degradation and de novo formation of nine major glucose degradation products during storage of peritoneal dialysis fluids.

ABSTRACT: Reactive glucose degradation products (GDPs) are formed during heat sterilization of glucose-containing peritoneal dialysis fluids (PDFs) and may induce adverse clinical effects. Long periods of storage and/or transport of PDFs before use may lead to de novo formation or degradation of GDPs. Therefore, the present study quantified the GDP profiles of single- and double-chamber PDFs during storage. Glucosone, 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxyglucosone-3-ene (3,4-DGE), glyoxal, methylglyoxal (MGO), acetaldehyde, formaldehyde, and 5-hydroxymethylfurfural (5-HMF) were quantified by two validated UHPLC-DAD methods after derivatization with o-phenylenediamine (dicarbonyls) or 2,4-dinitrophenylhydrazine (monocarbonyls). The PDFs were stored at 50 °C for 0, 1, 2, 4, 13, and 26 weeks. The total GDP concentration of single-chamber PDFs did not change considerably during storage (496.6 ± 16.0 µM, 0 weeks; 519.1 ± 13.1 µM, 26 weeks), but individual GDPs were affected differently. 3-DG (- 82.6 µM) and 3-DGal (- 71.3 µM) were degraded, whereas 5-HMF (+ 161.7 µM), glyoxal (+ 32.2 µM), and formaldehyde (+ 12.4 µM) accumulated between 0 and 26 weeks. Acetaldehyde, glucosone, MGO, and 3,4-DGE showed time-dependent formation and degradation. The GDP concentrations in double-chamber fluids were generally lower and differently affected by storage. In conclusion, the changes of GDP concentrations during storage should be considered for the evaluation of clinical effects of PDFs.

SUBMITTER: Gensberger-Reigl S

PROVIDER: S-EPMC8917136 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Degradation and de novo formation of nine major glucose degradation products during storage of peritoneal dialysis fluids.

Gensberger-Reigl Sabrina S Weigel Ingrid I Stützer Joachim J Auditore Andrea A Nikolaus Tim T Pischetsrieder Monika M

Scientific reports 20220311 1

Reactive glucose degradation products (GDPs) are formed during heat sterilization of glucose-containing peritoneal dialysis fluids (PDFs) and may induce adverse clinical effects. Long periods of storage and/or transport of PDFs before use may lead to de novo formation or degradation of GDPs. Therefore, the present study quantified the GDP profiles of single- and double-chamber PDFs during storage. Glucosone, 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxyglucosone-3-ene (3,4-DG ...[more]

PMID: 35277529

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Project description:IntroductionPeritoneal dialysis fluids (PDF) differ with respect to osmotic and buffer compound, and pH and glucose degradation products (GDP) content. The impact on peritoneal membrane integrity is still insufficiently described. We assessed global genomic effects of PDF in primary human peritoneal mesothelial cells (PMC) by whole genome analyses, quantitative real-time polymerase chain reaction (RT-PCR) and functional measurements.MethodsPMC isolated from omentum of non-uremic patients were incubated with conventional single chamber PDF (CPDF), lactate- (LPDF), bicarbonate- (BPDF) and bicarbonate/lactate-buffered double-chamber PDF (BLPDF), icodextrin (IPDF) and amino acid PDF (APDF), diluted 1:1 with medium. Affymetrix GeneChip U133Plus2.0 (Affymetrix, CA, USA) and quantitative RT-PCR were applied; cell viability was assessed by proliferation assays.ResultsThe number of differentially expressed genes compared to medium was 464 with APDF, 208 with CPDF, 169 with IPDF, 71 with LPDF, 45 with BPDF and 42 with BLPDF. Out of these genes 74%, 73%, 79%, 72%, 47% and 57% were downregulated. Gene Ontology (GO) term annotations mainly revealed associations with cell cycle (p = 10(-35)), cell division, mitosis, and DNA replication. One hundred and eighteen out of 249 probe sets detecting genes involved in cell cycle/division were suppressed, with APDF-treated PMC being affected the most regarding absolute number and degree, followed by CPDF and IPDF. Bicarbonate-containing PDF and BLPDF-treated PMC were affected the least. Quantitative RT-PCR measurements confirmed microarray findings for key cell cycle genes (CDK1/CCNB1/CCNE2/AURKA/KIF11/KIF14). Suppression was lowest for BPDF and BLPDF, they upregulated CCNE2 and SMC4. All PDF upregulated 3 out of 4 assessed cell cycle repressors (p53/BAX/p21). Cell viability scores confirmed gene expression results, being 79% of medium for LPDF, 101% for BLPDF, 51% for CPDF and 23% for IPDF. Amino acid-containing PDF (84%) incubated cells were as viable as BPDF (86%).ConclusionIn conclusion, PD solutions substantially differ with regard to their gene regulating profile and impact on vital functions of PMC, i.e. on cells known to be essential for peritoneal membrane homeostasis.

Project description:We created a new version of the nine-species benchmark originally described by Tran et al. [Tran2017]. To do so, we downloaded the RAW files from the same nine PRIDE projects (PXD005025, PXD004948, PXD004325, PXD004565, PXD004536, PXD004947, PXD003868, PXD004467, PXD004424) and converted them to MGF format using ThermoRawFileParser v1.3.4. We also downloaded the corresponding nine Uniprot reference proteomes and constructed a Tide index for each one, using Crux version 4.1. For one species (Vigna mungo), no reference proteome is available, so we used the proteome of the closely related species Vigna radiata. We allowed for the following variable modifications: Met oxidation, Asn deamidation, Gln deamidation, N-term acetylation, N-term carbamylation, N-term NH3 loss, and the combination of N-term carbamylation and NH3 loss by using the tide-index options "--mods-spec 1M+15.994915, 1N+0.984016, 1Q+0.984016 --nterm-peptide-mods-spec 1X+42.010565, 1X+43.005814, 1X-17.026549, 1X+25.980265 --max-mods 3". Note that one of the nine experiments (Mus musculus) was performed using SILAC labeling, but we searched without SILAC modifications and hence include in the benchmark only PSMs from unlabeled peptides. Each index also contains a shuffled decoy peptide corresponding to each target peptide. Each MGF file was searched against the corresponding index using the precursor window size and fragment bin tolerance specified in the original study. We used XCorr scoring with Tailor calibration, and we allowed for 1 isotope error in the selection of candidate peptides. All search results were then analyzed jointly per species using the Crux implementation of Percolator, with default parameters. For the benchmark, we retained all PSMs with Percolator q value < 0.01. We identified 13 MGF files with fewer than 100 accepted PSMs, and we eliminated all of these PSMs from the benchmark. We then post-processed the PSMs to eliminate peptides that are shared between species. Among the 229,984 unique peptides, we identified 3797 (1.7%) that occur in more than one species. For each such peptide, we selected one of the associated species at random and then eliminated all PSMs containing that peptide in other species. The final benchmark dataset consists of 2.8 million PSMs drawn from 343 RAW files, exported as annotated MGF files. Note: the initial data submission contained annotated MGF files without considering the N-terminal modifications mentioned above. The update available in the `/MSV000090982/updates/2024-05-14_woutb_71950b89/peak/9speciesbenchmark` FTP directory contains the corrected MGF files that are directly compatible with Casanovo. [Tran2017] Tran, N. H., Zhang, X., Xin, L., Shan, B. & Li, M. De novo peptide sequencing by deep learning. Proceedings of the National Academy of Sciences of the United States of America 31, 8247-8252 (2017).

Project description:Infections are major complications in peritoneal dialysis (PD) with a multifactorial etiology that comprises patient, microbial and dialytic factors. This study aimed at investigating the contribution of microbial biofilms on PD catheters to recalcitrant infections and their interplay with PD related-factors. A prospective observational study was performed on 47 patients attending Centro Hospitalar of Porto and Vila Nova de Gaia/Espinho to whom the catheter was removed due to infectious (n = 16) and non-infectious causes (n = 31). Microbial density on the catheter was assessed by culture methods and the isolated microorganisms identified by matrix-assisted laser desorption/ionization time-of-flight intact cell mass spectrometry. The effect of conventional and three biocompatible PD solutions on 16 Coagulase Negative Staphylococci (CNS) and 10 Pseudomonas aeruginosa strains planktonic growth and biofilm formation was evaluated. Cultures were positive in 87.5% of the catheters removed due infectious and 90.3% removed due to non-infectious causes. However, microbial yields were higher on the cuffs of catheters removed due to infection vs. non-infection. Staphylococci (CNS and Staphylococcus aureus) and P. aeruginosa were the predominant species: 32% and 20% in the infection and 43.3% and 22.7% in the non-infection group, respectively. In general, PD solutions had a detrimental effect on planktonic CNS and P. aeruginosa strains growth. All strains formed biofilms in the presence of PD solutions. The solutions had a more detrimental effect on P. aeruginosa than CNS strains. No major differences were observed between conventional and biocompatible solutions, although in icodextrin solution biofilm biomass was lower than in bicarbonate/lactate solution. Overall, we show that microbial biofilm is universal in PD catheters with the subclinical menace of Staphylococci and P. aeruginosa. Cuffs colonization may significantly contribute to infection. PD solutions differentially impact microbial species. This knowledge is important for the development of infection diagnosis, treatment and preventive strategies.

Dataset Information

Degradation and de novo formation of nine major glucose degradation products during storage of peritoneal dialysis fluids.

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Degradation and de novo formation of nine major glucose degradation products during storage of peritoneal dialysis fluids.

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