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Bruschi M.,Renal Childs Foundation | Bruschi M.,Nephrology and Dialysis Unit | Candiano G.,Nephrology and Dialysis Unit | Santucci L.,Renal Childs Foundation | And 7 more authors.
Nephrology Dialysis Transplantation | Year: 2011

Background. We compared the proteome profile of peritoneal effluents obtained with icodextrin (Ico) or glucose (Glu) in paediatric patients and defined the oxido-redox status of proteins.Methods. Sixteen patients underwent two 14-h daytime dwells performed on subsequent days with 7.5% Ico and 3.86% Glu solutions. Protein composition was analysed by two-dimensional electrophoresis and mass spectrometry; oxidized products were evaluated by cyanine labelling.Results. Peritoneal transport kinetics of β2-microglobulin and cystatin C was linear for both solutions, but was significantly higher with Ico than with Glu, suggesting a better efficiency for these molecules. There was a linear correlation between total protein removal during Ico and Glu dialysis in the same patient, suggesting that it is a function of peritoneal membrane characteristics. The ratio between proteins removed by Ico and by Glu solutions was higher at low removal rate. Image gel analysis revealed 1064 and 774 spots, respectively, in Ico and Glu solutions; 524 were common, and 314 were higher in Ico than Glu effluents. Analysis of protein oxido-redox status showed a greater amount of oxidized albumin in Ico dialysate that was correlated with lower serum levels.Conclusions. Our results indicate a better efficiency of Ico in removing small proteins. Removal of big proteins and their oxidized isoforms reflects potentially opposite effects. The long-term clinical consequences of removing also potentially important molecules are to be defined. © 2010 The Author.


Sano M.,University of Shiga Prefecture | Ferchaud-Roucher V.,Mass Spectrometry Core Facility | Kaeffer B.,University of Nantes | Poupeau G.,University of Nantes | And 2 more authors.
Amino Acids | Year: 2015

l-Tryptophan (l-Trp) is a precursor for serotonin (5-HT) and nicotinamide adenine dinucleotide (NAD) synthesis. Both 5-HT and NAD may impact energy metabolism during gestation given that recent studies have demonstrated that increased 5-HT production is crucial for increasing maternal insulin secretion, and that sirtuin, an NAD+-dependent protein deacetylase, regulates endocrine signaling. Infants born with intrauterine growth restriction (IUGR) are at a higher risk of metabolic disease once they reach adulthood. IUGR is associated with altered maternal–fetal amino acid transfer. Whether IUGR affects l-Trp metabolism in mother and fetus has not been fully elucidated. Recently, we developed an analytical method using stable isotope-labeled l-Trp to explore the metabolism of l-Trp and its main metabolites, l-kynurenine (l-Kyn), 5-HT and quinolinic acid (QA). In this study, dams submitted to dietary protein restriction throughout gestation received intravenous infusions of stable isotope-labeled 15N2-l-Trp to determine whether l-Trp metabolism is affected by IUGR. Samples were obtained from maternal, fetal and umbilical vein plasma, as well as the amniotic fluid (AF), placenta and liver of the mother and the fetus after isotope infusion. We observed evidence for active l-Trp transfer from mother to fetus, as well as de novo synthesis of 5-HT in the fetus. Plasma 5-HT was decreased in undernourished mothers. In IUGR fetuses, maternal–fetal l-Trp transfer remained unaffected, but conversion to QA was impaired, implying that NAD production also decreased. Whether such alterations in tryptophan metabolism during gestation have adverse consequences and contribute to the increased risk of metabolic disease in IUGR remains to be explored. © 2015 Springer-Verlag Wien


Kuster A.,University of Nantes | Kuster A.,Nantes University Hospital Center | Tea I.,University of Nantes | Ferchaud-Roucher V.,Mass Spectrometry Core Facility | And 9 more authors.
PLoS ONE | Year: 2011

Background: Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants. Objective: Our aim was to determine: 1) whether GSH depletion is present at the time of birth; and 2) whether it is associated with insufficient availability of cysteine (cys), the limiting GSH precursor, or a decreased capacity to synthesize GSH. Methodology: Sixteen mothers delivering very low birth weight infants (VLBW), and 16 mothers delivering healthy, full term neonates were enrolled. Immediately after birth, erythrocytes from umbilical vein, umbilical artery, and maternal blood were obtained to assess GSH [GSH] and cysteine [cys] concentrations, and the GSH synthesis rate was determined from the incorporation of labeled cysteine into GSH in isolated erythrocytes ex vivo, measured using gas chromatography mass spectrometry. Principal Findings: Compared with mothers delivering at full term, mothers delivering prematurely had markedly lower erythrocyte [GSH] and [cys] and these were significantly depressed in VLBW infants, compared with term neonates. A strong correlation was found between maternal and fetal GSH and cysteine levels. The capacity to synthesize GSH was as high in VLBW as in term infants. Conclusion: The current data demonstrate that: 1) GSH depletion is present at the time of birth in VLBW infants; 2) As VLBW neonates possess a fully active capacity to synthesize glutathione, the depletion may arise from inadequate cysteine availability, potentially due to maternal depletion. Further studies would be needed to determine whether maternal-fetal cysteine transfer is decreased in preterm infants, and, if so, whether cysteine supplementation of mothers at risk of delivering prematurely would strengthen antioxidant defense in preterm neonates. © 2011 Küster et al.


PubMed | University of Nantes, Mass Spectrometry Core Facility and University of Shiga Prefecture
Type: Journal Article | Journal: Amino acids | Year: 2016

L-Tryptophan (L-Trp) is a precursor for serotonin (5-HT) and nicotinamide adenine dinucleotide (NAD) synthesis. Both 5-HT and NAD may impact energy metabolism during gestation given that recent studies have demonstrated that increased 5-HT production is crucial for increasing maternal insulin secretion, and that sirtuin, an NAD(+)-dependent protein deacetylase, regulates endocrine signaling. Infants born with intrauterine growth restriction (IUGR) are at a higher risk of metabolic disease once they reach adulthood. IUGR is associated with altered maternal-fetal amino acid transfer. Whether IUGR affects L-Trp metabolism in mother and fetus has not been fully elucidated. Recently, we developed an analytical method using stable isotope-labeled L-Trp to explore the metabolism of L-Trp and its main metabolites, L-kynurenine (L-Kyn), 5-HT and quinolinic acid (QA). In this study, dams submitted to dietary protein restriction throughout gestation received intravenous infusions of stable isotope-labeled (15)N2-L-Trp to determine whether L-Trp metabolism is affected by IUGR. Samples were obtained from maternal, fetal and umbilical vein plasma, as well as the amniotic fluid (AF), placenta and liver of the mother and the fetus after isotope infusion. We observed evidence for active L-Trp transfer from mother to fetus, as well as de novo synthesis of 5-HT in the fetus. Plasma 5-HT was decreased in undernourished mothers. In IUGR fetuses, maternal-fetal L-Trp transfer remained unaffected, but conversion to QA was impaired, implying that NAD production also decreased. Whether such alterations in tryptophan metabolism during gestation have adverse consequences and contribute to the increased risk of metabolic disease in IUGR remains to be explored.

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