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Nelly Mauras - One of the best experts on this subject based on the ideXlab platform.
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Acute changes in blood glucose do not alter blood glutathione Synthesis in adolescents with poorly controlled type 1 diabetes mellitus
Metabolism, 2012Co-Authors: Dominique Darmaun, Susan Welch, Shiela Smith, Shawn Sweeten, Nelly MaurasAbstract:Depletion of blood glutathione (GSH), a key antioxidant, is associated with type 1 diabetes mellitus (T1D) and contributes to the pathophysiology of diabetes complications. The aim of the current study was to determine whether acute normalization of blood glucose would restore GSH kinetics in adolescents with poorly controlled T1D. Ten 16.9 +/- 1.5-year-old (SE) adolescents who had had T1D for 8.5 +/- 1.9 years and were free of complications but were in poor control (hemoglobin A(1c), 9.2% +/- 0.5%) received two 5-hour intravenous infusions of L-[3,3-H-2(2)]cysteine in the postabsorptive state on 2 sepaRate days after blood glucose had been maintained overnight at 246 +/- 24 mg/dL (hyperglycemia) or 118 +/- 23 mg/dL (euglycemia) using intravenous insulin infusion. Blood GSH Fractional Synthesis Rates were determined by mass spectrometry from H-2(2)-cysteine incorporation into GSH. Neither blood GSH (551 +/- 169 vs 541 +/- 232 mu mol/L, P = .629) nor GSH Fractional Synthesis Rate (84% +/- 30% vs 82% +/- 33% d(-1), P = .965) was altered by the short-term change in glycemic control. This finding suggests that, in adolescents with poorly controlled T1D, either (a) blood glucose per se does not regulate GSH metabolism or (b) GSH may only respond to sustained, more chronic changes in blood glucose level. (C) 2012 Elsevier Inc. All rights reserved.
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Acute changes in blood glucose do not alter blood glutathione Synthesis in adolescents with poorly controlled type 1 diabetes mellitus
Metabolism: clinical and experimental, 2011Co-Authors: Dominique Darmaun, Susan Welch, Shawn Sweeten, Shiela D. Smith, Nelly MaurasAbstract:Abstract Depletion of blood glutathione (GSH), a key antioxidant, is associated with type 1 diabetes mellitus (T1D) and contributes to the pathophysiology of diabetes complications. The aim of the current study was to determine whether acute normalization of blood glucose would restore GSH kinetics in adolescents with poorly controlled T1D. Ten 16.9 ± 1.5-year-old (SE) adolescents who had had T1D for 8.5 ± 1.9 years and were free of complications but were in poor control (hemoglobin A1c, 9.2% ± 0.5%) received two 5-hour intravenous infusions of L-[3,3-2H2]cysteine in the postabsorptive state on 2 sepaRate days after blood glucose had been maintained overnight at 246 ± 24 mg/dL (hyperglycemia) or 118 ± 23 mg/dL (euglycemia) using intravenous insulin infusion. Blood GSH Fractional Synthesis Rates were determined by mass spectrometry from 2H2-cysteine incorporation into GSH. Neither blood GSH (551 ± 169 vs 541 ± 232 μmol/L, P = .629) nor GSH Fractional Synthesis Rate (84% ± 30% vs 82% ± 33% d−1, P = .965) was altered by the short-term change in glycemic control. This finding suggests that, in adolescents with poorly controlled T1D, either (a) blood glucose per se does not regulate GSH metabolism or (b) GSH may only respond to sustained, more chronic changes in blood glucose level.
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response of Fractional Synthesis Rate fsr of fibrinogen concentration of d dimer and fibrinolytic balance to physical activity based intervention in obese children
Journal of Thrombosis and Haemostasis, 2008Co-Authors: Prabhakaran Balagopal, Shawn Sweeten, Nelly Mauras, Donald George, Karl J Mann, Hossein N. Yarandi, Douglas E. VaughanAbstract:To cite this article: Balagopal P, George D, Sweeten S, Mann KJ, Yarandi H, Mauras N, Vaughan DE. Response of Fractional Synthesis Rate (FSR) of fibrinogen, concentration of D-dimer and fibrinolytic balance to physical activity-based intervention in obese children. J Thromb Haemost 2008; 6: 1296‐303. Summary. Background: Physical activity-induced reduction in obesity-related hyperfibrinogenemia in children has been reported. The underlying mechanisms remain elusive. Further, the effect of such interventions on fibrinolysis in children is scarce. Objectives: To investigate in obese children, before and after a physical activity-based intervention: (i) the mechanistic role of Fractional Synthesis Rate (FSR) of fibrinogen in the reduction of hyperfibrinogenemia; and (ii) the changes in fibrinolytic factors. Methods: Subjects included 21 (age > 14 95%tile for age and sex and six lean, BMI <85%tile). After baseline measurements of FSR of fibrinogen, and concentrations of fibrinogen, D-dimer, PAI-1 and t-PA in all children, studies were repeated after a 3-month randomized controlled physical activity-based lifestyle intervention in obese children only. Results: FSR of fibrinogen was higher (P = 0.002) in the obese (vs. lean) group, which was reduced (P = 0.001) after intervention. This almost completely accounted for the reduction in obesity-related hyperfibrinogenemia. High levels of D-dimer decreased (P = 0.001) after intervention, whereas fibrinolysis was not enhanced. Conclusions: The direct reduction in the FSR of fibrinogen and the remarkable correlation between the magnitudes of reduction in fibrinogen FSR and concentration signify a mechanistic role for FSR in the regulation of physical activity-induced reversal of hyperfibrinogenemia in obese children. The congruent reductions in the FSR of fibrinogen and the concentrations of fibrinogen and D-dimer in response to intervention despite depressed fibrinolysis suggest an overall improvement in the hypercoagulable state in obese children with physical activity-based lifestyle intervention.
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Response of Fractional Synthesis Rate (FSR) of fibrinogen, concentration of D-dimer and fibrinolytic balance to physical activity-based intervention in obese children
Journal of thrombosis and haemostasis : JTH, 2008Co-Authors: Prabhakaran Balagopal, Shawn Sweeten, Nelly Mauras, Donald George, Karl J Mann, Hossein N. Yarandi, Douglas E. VaughanAbstract:To cite this article: Balagopal P, George D, Sweeten S, Mann KJ, Yarandi H, Mauras N, Vaughan DE. Response of Fractional Synthesis Rate (FSR) of fibrinogen, concentration of D-dimer and fibrinolytic balance to physical activity-based intervention in obese children. J Thromb Haemost 2008; 6: 1296‐303. Summary. Background: Physical activity-induced reduction in obesity-related hyperfibrinogenemia in children has been reported. The underlying mechanisms remain elusive. Further, the effect of such interventions on fibrinolysis in children is scarce. Objectives: To investigate in obese children, before and after a physical activity-based intervention: (i) the mechanistic role of Fractional Synthesis Rate (FSR) of fibrinogen in the reduction of hyperfibrinogenemia; and (ii) the changes in fibrinolytic factors. Methods: Subjects included 21 (age > 14 95%tile for age and sex and six lean, BMI
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Evidence for AcceleRated Rates of Glutathione Utilization and Glutathione Depletion in Adolescents With Poorly Controlled Type 1 Diabetes
Diabetes, 2004Co-Authors: Dominique Darmaun, Susan Welch, Shawn Sweeten, Shiela D. Smith, Brenda K. Sager, Nelly MaurasAbstract:Depletion of glutathione, an important antioxidant present in red cells, has been reported in type 1 diabetes, but the mechanism of this depletion has not been fully characterized. Glutathione depletion can occur through decreased Synthesis, increased utilization, or a combination of both. To address this issue, 5-h infusions of l-[3,3-2H2]cysteine were performed in 16 diabetic adolescents divided into a well-controlled and a poorly controlled group and in eight healthy nondiabetic teenagers as control subjects (HbA1c 6.3 ± 0.2, 10.5 ± 0.6, and 4.8 ± 0.1%, respectively). Glutathione Fractional Synthesis Rate was determined from 2H2-cysteine incorporation into blood glutathione. We observed that 1 ) erythrocyte cysteine concentration was 41% lower in poorly controlled patients compared with well-controlled patients ( P = 0.009); 2 ) erythrocyte glutathione concentration was ∼29% and ∼36% lower in well-controlled and poorly controlled patients compared with healthy volunteers; and 3 ) the Fractional Synthesis Rate of glutathione, although similar in well-controlled and healthy subjects (83 ± 14 vs. 82 ± 11% per day), was substantially higher in the poorly controlled group (141 ± 23% per day, P = 0.038). These findings suggest that in diabetic adolescents, poor control is associated with a significant depletion of blood glutathione and cysteine, due to increased Rates of glutathione utilization. This weakened antioxidant defense may play a role in the pathogenesis of diabetes complications.
Dominique Darmaun - One of the best experts on this subject based on the ideXlab platform.
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Acute changes in blood glucose do not alter blood glutathione Synthesis in adolescents with poorly controlled type 1 diabetes mellitus
Metabolism, 2012Co-Authors: Dominique Darmaun, Susan Welch, Shiela Smith, Shawn Sweeten, Nelly MaurasAbstract:Depletion of blood glutathione (GSH), a key antioxidant, is associated with type 1 diabetes mellitus (T1D) and contributes to the pathophysiology of diabetes complications. The aim of the current study was to determine whether acute normalization of blood glucose would restore GSH kinetics in adolescents with poorly controlled T1D. Ten 16.9 +/- 1.5-year-old (SE) adolescents who had had T1D for 8.5 +/- 1.9 years and were free of complications but were in poor control (hemoglobin A(1c), 9.2% +/- 0.5%) received two 5-hour intravenous infusions of L-[3,3-H-2(2)]cysteine in the postabsorptive state on 2 sepaRate days after blood glucose had been maintained overnight at 246 +/- 24 mg/dL (hyperglycemia) or 118 +/- 23 mg/dL (euglycemia) using intravenous insulin infusion. Blood GSH Fractional Synthesis Rates were determined by mass spectrometry from H-2(2)-cysteine incorporation into GSH. Neither blood GSH (551 +/- 169 vs 541 +/- 232 mu mol/L, P = .629) nor GSH Fractional Synthesis Rate (84% +/- 30% vs 82% +/- 33% d(-1), P = .965) was altered by the short-term change in glycemic control. This finding suggests that, in adolescents with poorly controlled T1D, either (a) blood glucose per se does not regulate GSH metabolism or (b) GSH may only respond to sustained, more chronic changes in blood glucose level. (C) 2012 Elsevier Inc. All rights reserved.
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Acute changes in blood glucose do not alter blood glutathione Synthesis in adolescents with poorly controlled type 1 diabetes mellitus
Metabolism: clinical and experimental, 2011Co-Authors: Dominique Darmaun, Susan Welch, Shawn Sweeten, Shiela D. Smith, Nelly MaurasAbstract:Abstract Depletion of blood glutathione (GSH), a key antioxidant, is associated with type 1 diabetes mellitus (T1D) and contributes to the pathophysiology of diabetes complications. The aim of the current study was to determine whether acute normalization of blood glucose would restore GSH kinetics in adolescents with poorly controlled T1D. Ten 16.9 ± 1.5-year-old (SE) adolescents who had had T1D for 8.5 ± 1.9 years and were free of complications but were in poor control (hemoglobin A1c, 9.2% ± 0.5%) received two 5-hour intravenous infusions of L-[3,3-2H2]cysteine in the postabsorptive state on 2 sepaRate days after blood glucose had been maintained overnight at 246 ± 24 mg/dL (hyperglycemia) or 118 ± 23 mg/dL (euglycemia) using intravenous insulin infusion. Blood GSH Fractional Synthesis Rates were determined by mass spectrometry from 2H2-cysteine incorporation into GSH. Neither blood GSH (551 ± 169 vs 541 ± 232 μmol/L, P = .629) nor GSH Fractional Synthesis Rate (84% ± 30% vs 82% ± 33% d−1, P = .965) was altered by the short-term change in glycemic control. This finding suggests that, in adolescents with poorly controlled T1D, either (a) blood glucose per se does not regulate GSH metabolism or (b) GSH may only respond to sustained, more chronic changes in blood glucose level.
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Simultaneous determination of glutathione and cysteine concentrations and 2H enrichments in microvolumes of neonatal blood using gas chromatography - mass spectrometry
Analytical and Bioanalytical Chemistry, 2008Co-Authors: Alice Kuster, Shawn Sweeten, Illa Téa, Jean-christophe Rozé, Richard J. Robins, Dominique DarmaunAbstract:A method is described whereby the concentrations and 2H isotope enrichment of glutathione (GSH) and cysteine can be simultaneously determined in a single gas chromatography–mass spectrometry run following derivatization as their N,S-ethoxycarbonyl methyl esters. Improvements of the derivatization protocol and the use of a short gas chromatography column combined with single-ion monitoring allow for rapid quantification of these parameters with acceptable precision and reproducibility (coefficient of variation less than 5%). The method makes possible their quantitative measurement in very small volumes (50 μL) of human umbilical cord blood, and is thus suitable for determining the cysteine and GSH concentrations and 2H isotope enrichments in blood samples from neonates or in other conditions in which sample size is restricted. It is shown that the Fractional Synthesis Rate of human umbilical erythrocyte lysates in vitro is several-fold greater than that measured in vivo.
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Determination of C-13 isotopic enrichment of glutathione and glycine by gas chromatography/combustion/isotope ratio mass spectrometry after formation of the N- or N,S-ethoxycarbonyl methyl ester derivatives
Rapid Communications in Mass Spectrometry, 2007Co-Authors: Illa Téa, Dominique Darmaun, Alice Kuster, V. Ferchaud-roucher, R.j. RobinsAbstract:The depletion of glutathione (GSH) reported in very-low-birth-weight infants is implicated in several pathologies, especially if deficiency occurs during foetal development. The cause of this depletion is suggested to be modification of GSH turnover. To probe the role of GSH, a reliable non-invasive method adapted to very-low-birth-weight infants is required. In this paper, we report the preparation of the N,S-ethoxycarbonyl methyl ester derivatives of GSH and glycine and their application to the measurement of C-13/C-12 ratios at natural abundance in erythrocyte samples by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). The technique allowed the determination of C-13/C-12 ratios at natural abundance with a precision < 3% and within-day and between-day variabilities both < 4%. The method is able to determine accuRately low C-13-enrichments in GSH (0.00241 to 0.00753 Atom Percent Excess) in erythrocyte extracts following incubation with C-13-glycine at low specific enrichment (approx. 1.5 atom %). Excellent agreement was obtained between the calculated GSH Fractional Synthesis Rate (FSR) in human adult blood (approx. 300% day(-1)) using the low-enrichment C-13-glycine/GC/C/IRMS protocol and that using highly enriched C-13-glycine (99 atom %)/GC/MS with the same derivative. The GC/C/IRMS method was shown to be suitable to measure the in vitro GSH FSR (200-660% day(-1)) in human venous and arterial blood from the umbilical cord. This approach provides a good tool for studying the turnover of GSH in vitro in infants, allowing both the use of minimal amounts of tracer and negligible perturbation of endogenous precursor pools
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Evidence for AcceleRated Rates of Glutathione Utilization and Glutathione Depletion in Adolescents With Poorly Controlled Type 1 Diabetes
Diabetes, 2004Co-Authors: Dominique Darmaun, Susan Welch, Shawn Sweeten, Shiela D. Smith, Brenda K. Sager, Nelly MaurasAbstract:Depletion of glutathione, an important antioxidant present in red cells, has been reported in type 1 diabetes, but the mechanism of this depletion has not been fully characterized. Glutathione depletion can occur through decreased Synthesis, increased utilization, or a combination of both. To address this issue, 5-h infusions of l-[3,3-2H2]cysteine were performed in 16 diabetic adolescents divided into a well-controlled and a poorly controlled group and in eight healthy nondiabetic teenagers as control subjects (HbA1c 6.3 ± 0.2, 10.5 ± 0.6, and 4.8 ± 0.1%, respectively). Glutathione Fractional Synthesis Rate was determined from 2H2-cysteine incorporation into blood glutathione. We observed that 1 ) erythrocyte cysteine concentration was 41% lower in poorly controlled patients compared with well-controlled patients ( P = 0.009); 2 ) erythrocyte glutathione concentration was ∼29% and ∼36% lower in well-controlled and poorly controlled patients compared with healthy volunteers; and 3 ) the Fractional Synthesis Rate of glutathione, although similar in well-controlled and healthy subjects (83 ± 14 vs. 82 ± 11% per day), was substantially higher in the poorly controlled group (141 ± 23% per day, P = 0.038). These findings suggest that in diabetic adolescents, poor control is associated with a significant depletion of blood glutathione and cysteine, due to increased Rates of glutathione utilization. This weakened antioxidant defense may play a role in the pathogenesis of diabetes complications.
Gerrit Van Hall - One of the best experts on this subject based on the ideXlab platform.
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determination of human muscle protein Fractional Synthesis Rate an evaluation of different mass spectrometry techniques and considerations for tracer choice
Journal of Mass Spectrometry, 2014Co-Authors: Andreas Bornø, Carl J. Hulston, Gerrit Van HallAbstract:In the present study, different MS methods for the determination of human muscle protein Fractional Synthesis Rate (FSR) using [ring-13C6]phenylalanine as a tracer were evaluated. Because the turnover Rate of human skeletal muscle is slow, only minute quantities of the stable isotopically labeled amino acid will be incorpoRated within the few hours of a typical laboratory experiment. GC combustion isotope ratio MS (GC-C-IRMS) has thus far been considered the ‘gold’ standard for the precise measurements of these low enrichment levels. However, advances in liquid chromatography-tandem MS (LC-MS/MS) and GC-tandem MS (GC-MS/MS) have made these techniques an option for human muscle FSR measurements. Human muscle biopsies were freeze dried, cleaned, and hydrolyzed, and the amino acids derivatized using either N-acetyl-n-propyl, phenylisothiocyanate, or N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) for GC-C-IRMS, LC-MS/MS, and GC-MS/MS analysis, respectively. A second derivative, heptafluorobutyric acid (HFBA), was also used for GC-MS/MS analysis as an alternative for MTBSTFA. The machine reproducibility or the coefficients of variation for delta tracer-tracee-ratio measurements (delta tracer-tracee-ratio values around 0.0002) were 2.6%, 4.1%, and 10.9% for GC-C-IRMS, LC-MS/MS, and GC-MS/MS (MTBSTFA), respectively. FSR determined with LC-MS/MS compared well with GC-C-IRMS and so did the GC-MS/MS when using the HFBA derivative (linear fit Y = 1.08 ± 0.10, X + 0.0049 ± 0.0061, r = 0.89 ± 0.01, P < 0.0001). In conclusion, (1) IRMS still offers the most precise measurement of human muscle FSR, (2) LC-MS/MS comes quite close and is a good alternative when tissue quantities are too small for GC-C-IRMS, and (3) If GC-MS/MS is to be used, then the HFBA derivative should be used instead of MTBSTFA, which gave unacceptably high variability. Copyright © 2014 John Wiley & Sons, Ltd.
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Determination of human muscle protein Fractional Synthesis Rate: an evaluation of different mass spectrometry techniques and considerations for tracer choice.
Journal of mass spectrometry : JMS, 2014Co-Authors: Andreas Bornø, Carl J. Hulston, Gerrit Van HallAbstract:In the present study, different MS methods for the determination of human muscle protein Fractional Synthesis Rate (FSR) using [ring-13C6]phenylalanine as a tracer were evaluated. Because the turnover Rate of human skeletal muscle is slow, only minute quantities of the stable isotopically labeled amino acid will be incorpoRated within the few hours of a typical laboratory experiment. GC combustion isotope ratio MS (GC-C-IRMS) has thus far been considered the ‘gold’ standard for the precise measurements of these low enrichment levels. However, advances in liquid chromatography-tandem MS (LC-MS/MS) and GC-tandem MS (GC-MS/MS) have made these techniques an option for human muscle FSR measurements. Human muscle biopsies were freeze dried, cleaned, and hydrolyzed, and the amino acids derivatized using either N-acetyl-n-propyl, phenylisothiocyanate, or N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) for GC-C-IRMS, LC-MS/MS, and GC-MS/MS analysis, respectively. A second derivative, heptafluorobutyric acid (HFBA), was also used for GC-MS/MS analysis as an alternative for MTBSTFA. The machine reproducibility or the coefficients of variation for delta tracer-tracee-ratio measurements (delta tracer-tracee-ratio values around 0.0002) were 2.6%, 4.1%, and 10.9% for GC-C-IRMS, LC-MS/MS, and GC-MS/MS (MTBSTFA), respectively. FSR determined with LC-MS/MS compared well with GC-C-IRMS and so did the GC-MS/MS when using the HFBA derivative (linear fit Y = 1.08 ± 0.10, X + 0.0049 ± 0.0061, r = 0.89 ± 0.01, P
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Contraction intensity and feeding affect collagen and myofibrillar protein Synthesis Rates differently in human skeletal muscle.
American journal of physiology. Endocrinology and metabolism, 2009Co-Authors: Lars Holm, Gerrit Van Hall, Adam J. Rose, Benjamin F. Miller, Simon Doessing, Erik A. Richter, Michael KjaerAbstract:Exercise stimulates muscle protein Fractional Synthesis Rate (FSR), but the importance of contractile intensity and whether it interplays with feeding is not understood. This was investigated follo...
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High triacylglycerol turnover Rate in human skeletal muscle.
The Journal of physiology, 2004Co-Authors: Massimo Sacchetti, Bengt Saltin, David B Olsen, Gerrit Van HallAbstract:In the present study we investigated the relationship between plasma fatty acids (FA) and intramuscular triacylglycerol (IMTAG) kinetics of healthy volunteers. With this aim [U-(13)C]-palmitate was infused for 10 h and FA kinetics determined across the leg. In addition, the Rate of FA incorporation into IMTAG in vastus lateralis muscle was determined during two consecutive 4-h periods (2-6 h and 6-10 h). Fifty to sixty per cent of the FA taken up from the circulation were esterified into IMTAG, whereas 32 and 42% were oxidized between 2-6 and 6-10 h, respectively. IMTAG Fractional Synthesis Rate was 3.4 +/- 0.8% h(-1) and did not change between the two 4- h periods, despite an increase in arterial FA concentration (34%, P < 0.01). IMTAG concentration was also unchanged, implying that the IMTAG Fractional Synthesis Rate was balanced by an equal Rate of breakdown. FA oxidation increased over time, which could be due to the observed decline in plasma insulin concentration (-74%, P < 0.01). In conclusion, a substantial fraction of the fatty acids entering skeletal muscle in post-absorptive healthy individuals is esterified into IMTAG, due to its high turnover Rate (29 h pool(-1)). An increase in FA level, as a consequence of short-term fasting, does not seem to increase IMTAG Synthesis Rate and pool size.
Shawn Sweeten - One of the best experts on this subject based on the ideXlab platform.
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Acute changes in blood glucose do not alter blood glutathione Synthesis in adolescents with poorly controlled type 1 diabetes mellitus
Metabolism, 2012Co-Authors: Dominique Darmaun, Susan Welch, Shiela Smith, Shawn Sweeten, Nelly MaurasAbstract:Depletion of blood glutathione (GSH), a key antioxidant, is associated with type 1 diabetes mellitus (T1D) and contributes to the pathophysiology of diabetes complications. The aim of the current study was to determine whether acute normalization of blood glucose would restore GSH kinetics in adolescents with poorly controlled T1D. Ten 16.9 +/- 1.5-year-old (SE) adolescents who had had T1D for 8.5 +/- 1.9 years and were free of complications but were in poor control (hemoglobin A(1c), 9.2% +/- 0.5%) received two 5-hour intravenous infusions of L-[3,3-H-2(2)]cysteine in the postabsorptive state on 2 sepaRate days after blood glucose had been maintained overnight at 246 +/- 24 mg/dL (hyperglycemia) or 118 +/- 23 mg/dL (euglycemia) using intravenous insulin infusion. Blood GSH Fractional Synthesis Rates were determined by mass spectrometry from H-2(2)-cysteine incorporation into GSH. Neither blood GSH (551 +/- 169 vs 541 +/- 232 mu mol/L, P = .629) nor GSH Fractional Synthesis Rate (84% +/- 30% vs 82% +/- 33% d(-1), P = .965) was altered by the short-term change in glycemic control. This finding suggests that, in adolescents with poorly controlled T1D, either (a) blood glucose per se does not regulate GSH metabolism or (b) GSH may only respond to sustained, more chronic changes in blood glucose level. (C) 2012 Elsevier Inc. All rights reserved.
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Acute changes in blood glucose do not alter blood glutathione Synthesis in adolescents with poorly controlled type 1 diabetes mellitus
Metabolism: clinical and experimental, 2011Co-Authors: Dominique Darmaun, Susan Welch, Shawn Sweeten, Shiela D. Smith, Nelly MaurasAbstract:Abstract Depletion of blood glutathione (GSH), a key antioxidant, is associated with type 1 diabetes mellitus (T1D) and contributes to the pathophysiology of diabetes complications. The aim of the current study was to determine whether acute normalization of blood glucose would restore GSH kinetics in adolescents with poorly controlled T1D. Ten 16.9 ± 1.5-year-old (SE) adolescents who had had T1D for 8.5 ± 1.9 years and were free of complications but were in poor control (hemoglobin A1c, 9.2% ± 0.5%) received two 5-hour intravenous infusions of L-[3,3-2H2]cysteine in the postabsorptive state on 2 sepaRate days after blood glucose had been maintained overnight at 246 ± 24 mg/dL (hyperglycemia) or 118 ± 23 mg/dL (euglycemia) using intravenous insulin infusion. Blood GSH Fractional Synthesis Rates were determined by mass spectrometry from 2H2-cysteine incorporation into GSH. Neither blood GSH (551 ± 169 vs 541 ± 232 μmol/L, P = .629) nor GSH Fractional Synthesis Rate (84% ± 30% vs 82% ± 33% d−1, P = .965) was altered by the short-term change in glycemic control. This finding suggests that, in adolescents with poorly controlled T1D, either (a) blood glucose per se does not regulate GSH metabolism or (b) GSH may only respond to sustained, more chronic changes in blood glucose level.
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response of Fractional Synthesis Rate fsr of fibrinogen concentration of d dimer and fibrinolytic balance to physical activity based intervention in obese children
Journal of Thrombosis and Haemostasis, 2008Co-Authors: Prabhakaran Balagopal, Shawn Sweeten, Nelly Mauras, Donald George, Karl J Mann, Hossein N. Yarandi, Douglas E. VaughanAbstract:To cite this article: Balagopal P, George D, Sweeten S, Mann KJ, Yarandi H, Mauras N, Vaughan DE. Response of Fractional Synthesis Rate (FSR) of fibrinogen, concentration of D-dimer and fibrinolytic balance to physical activity-based intervention in obese children. J Thromb Haemost 2008; 6: 1296‐303. Summary. Background: Physical activity-induced reduction in obesity-related hyperfibrinogenemia in children has been reported. The underlying mechanisms remain elusive. Further, the effect of such interventions on fibrinolysis in children is scarce. Objectives: To investigate in obese children, before and after a physical activity-based intervention: (i) the mechanistic role of Fractional Synthesis Rate (FSR) of fibrinogen in the reduction of hyperfibrinogenemia; and (ii) the changes in fibrinolytic factors. Methods: Subjects included 21 (age > 14 95%tile for age and sex and six lean, BMI <85%tile). After baseline measurements of FSR of fibrinogen, and concentrations of fibrinogen, D-dimer, PAI-1 and t-PA in all children, studies were repeated after a 3-month randomized controlled physical activity-based lifestyle intervention in obese children only. Results: FSR of fibrinogen was higher (P = 0.002) in the obese (vs. lean) group, which was reduced (P = 0.001) after intervention. This almost completely accounted for the reduction in obesity-related hyperfibrinogenemia. High levels of D-dimer decreased (P = 0.001) after intervention, whereas fibrinolysis was not enhanced. Conclusions: The direct reduction in the FSR of fibrinogen and the remarkable correlation between the magnitudes of reduction in fibrinogen FSR and concentration signify a mechanistic role for FSR in the regulation of physical activity-induced reversal of hyperfibrinogenemia in obese children. The congruent reductions in the FSR of fibrinogen and the concentrations of fibrinogen and D-dimer in response to intervention despite depressed fibrinolysis suggest an overall improvement in the hypercoagulable state in obese children with physical activity-based lifestyle intervention.
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Response of Fractional Synthesis Rate (FSR) of fibrinogen, concentration of D-dimer and fibrinolytic balance to physical activity-based intervention in obese children
Journal of thrombosis and haemostasis : JTH, 2008Co-Authors: Prabhakaran Balagopal, Shawn Sweeten, Nelly Mauras, Donald George, Karl J Mann, Hossein N. Yarandi, Douglas E. VaughanAbstract:To cite this article: Balagopal P, George D, Sweeten S, Mann KJ, Yarandi H, Mauras N, Vaughan DE. Response of Fractional Synthesis Rate (FSR) of fibrinogen, concentration of D-dimer and fibrinolytic balance to physical activity-based intervention in obese children. J Thromb Haemost 2008; 6: 1296‐303. Summary. Background: Physical activity-induced reduction in obesity-related hyperfibrinogenemia in children has been reported. The underlying mechanisms remain elusive. Further, the effect of such interventions on fibrinolysis in children is scarce. Objectives: To investigate in obese children, before and after a physical activity-based intervention: (i) the mechanistic role of Fractional Synthesis Rate (FSR) of fibrinogen in the reduction of hyperfibrinogenemia; and (ii) the changes in fibrinolytic factors. Methods: Subjects included 21 (age > 14 95%tile for age and sex and six lean, BMI
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Simultaneous determination of glutathione and cysteine concentrations and 2H enrichments in microvolumes of neonatal blood using gas chromatography - mass spectrometry
Analytical and Bioanalytical Chemistry, 2008Co-Authors: Alice Kuster, Shawn Sweeten, Illa Téa, Jean-christophe Rozé, Richard J. Robins, Dominique DarmaunAbstract:A method is described whereby the concentrations and 2H isotope enrichment of glutathione (GSH) and cysteine can be simultaneously determined in a single gas chromatography–mass spectrometry run following derivatization as their N,S-ethoxycarbonyl methyl esters. Improvements of the derivatization protocol and the use of a short gas chromatography column combined with single-ion monitoring allow for rapid quantification of these parameters with acceptable precision and reproducibility (coefficient of variation less than 5%). The method makes possible their quantitative measurement in very small volumes (50 μL) of human umbilical cord blood, and is thus suitable for determining the cysteine and GSH concentrations and 2H isotope enrichments in blood samples from neonates or in other conditions in which sample size is restricted. It is shown that the Fractional Synthesis Rate of human umbilical erythrocyte lysates in vitro is several-fold greater than that measured in vivo.
Peter J. Garlick - One of the best experts on this subject based on the ideXlab platform.
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Growth hormone does not affect albumin Synthesis in the critically ill
Intensive Care Medicine, 2001Co-Authors: Hans Barle, Pia Essén, Margaret A. Mcnurlan, Peter J. Garlick, Lena Gamrin, Jan WernermanAbstract:Objective : To study the effect of growth hormone (GH) on albumin Synthesis in critically ill patients. Design : Prospective randomized controlled study. Setting : Two intensive care units, university hospital and county hospital, respectively. Patients : Twenty-two critically ill patients in the intensive care unit. Interventions : Albumin Synthesis was measured twice in each patient, with a 5-day interval. The patients in the control group ( n =11) received standard intensive care unit (ICU) treatment between measurements, whereas those in the GH group ( n =11) also received 0.3 U/kg daily of human recombinant GH. Measurements and results : Albumin Synthesis was measured by labeling with L -[^2H_5]phenylalanine. In the control group, the Fractional Synthesis Rate (FSR) of albumin was 16.3±4.1%/day (mean and SD) in the first measurement and 15.7±4.2%/day 5 days later (NS), whereas in the GH group the corresponding values were 17.0±4.7%/day and 16.7±5.5%/day (NS). The calculated absolute Synthesis Rates of albumin, based on FSR and intravascular albumin mass, also showed no effect of GH. Conclusion : Albumin Synthesis Rates were consistently higher in the two groups of critically ill patients than previously reported values in healthy subjects. However, GH treatment for 5 days neither stimulated nor inhibited albumin Synthesis Rates in these critically ill patients.
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Inhibition of liver protein Synthesis during laparoscopic surgery.
The American journal of physiology, 1999Co-Authors: H. Barle, Björn Nyberg, Stig Ramel, Pia Essén, Margaret A. Mcnurlan, Jan Wernerman, Peter J. GarlickAbstract:Previous studies have indicated that laparoscopic surgery is associated with a decline in liver protein Synthesis. In this study, the Fractional Synthesis Rate (FSR) of total liver protein and albu...
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The Synthesis Rates of total liver protein and plasma albumin determined simultaneously in vivo in humans
Hepatology (Baltimore Md.), 1997Co-Authors: H. Barle, Margaret A. Mcnurlan, B. Nyberg, P. Essén, K. Andersson, J. Wernerman, Peter J. GarlickAbstract:Abstract Although the metabolism of liver-derived plasma proteins such as albumin has been extensively studied, human hepatic protein Synthesis as a whole has not been well characterized, because a reproducible model for obtaining human liver tissue has not been available. In this study, the Fractional Synthesis Rates of total liver protein and albumin in vivo were determined simultaneously in nine subjects undergoing elective laparoscopic cholecystectomy. L -[ 2 H 5 ]phenylalanine (45 mg/kg body wt) was administered for 10 minutes intravenously. Blood samples were collected at regular intervals for 90 minutes and a liver biopsy specimen was taken at 35 +/- 7 minutes. The enrichments of plasma free phenylalanine, plasma albumin, and total liver protein were measured with gas chromatography mass spectrometry (GC-MS). The Fractional Synthesis Rate (FSR) of total liver protein was 24.7 +/- 3.1 %/d (mean +/- SD), and that of albumin was 5.9 +/-1.2%/d. The amount of albumin synthesized per day (absolute Synthesis Rate, ASR) was 109 +/- 21 mg/kg body wt. No correlation between FSR of total liver protein and ASR of albumin was found. It is concluded that the technique of obtaining liver tissue specimens during laparoscopic surgery may serve as a human in vivo model to study total liver protein Synthesis. The Fractional Synthesis Rate of total liver proteins (stationary and exported), equals approximately 25% of the liver protein content daily. Within the range of values of this study, the absolute Synthesis Rate of albumin was not correlated to the Fractional Synthesis Rate of total liver protein. (Hepatology 1997 Jan;25(1):154-8)
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The effects of short-term parenteral nutrition on human liver protein and amino acid metabolism during laparoscopic surgery.
JPEN. Journal of parenteral and enteral nutrition, 1997Co-Authors: H. Barle, Björn Nyberg, Pia Essén, Margaret A. Mcnurlan, Jan Wernerman, K. Andersson, Peter J. GarlickAbstract:Background: This study was undertaken to elucidate the specific effects of short-term artificial nutrition on human liver protein metabolism. Methods: Thirty patients undergoing elective laparoscopic cholecystectomy were studied: a control group (n = 16) and a group that received total parenteral nutrition (TPN; n = 14). The nutrition consisted of a balanced IV solution of nutrients (17.5 nonprotein kcal/kg body wt, 50% fat, 50% carbohydRates, and 0.1 gN/kg) that was discontinued when the investigation was finished, after a total infusion time of 8.6 ± 1.0 hours. A liver biopsy specimen was taken as soon as possible after surgery was started, for the determination of the free hepatic amino acid concentrations. In 16 of the patients, L-[ 2H5]phenylalanine was given by IV to determine the Fractional Synthesis Rate of total liver protein in a second liver biopsy specimen taken approximately 30 minutes later. Results: The Fractional Synthesis Rate of total liver protein was 15.2% ± 4.7%/d in the TPN group (n ...
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Albumin but not fibrinogen Synthesis correlates with galactose elimination capacity in patients with cirrhosis of the liver
Hepatology (Baltimore Md.), 1996Co-Authors: P E Ballmer, Margaret A. Mcnurlan, J Reichen, A B Sterchi, S.e. Anderson, Peter J. GarlickAbstract:Abstract Albumin and fibrinogen Synthesis Rates were measured in 15 subjects with different clinical stages of postviral cirrhosis and compared with galactose elimination capacity and aminopyrin breath test. Forty-three mg per kg body weight [ 2 H 5 ring]phenylalanine with an isotopic enrichment of 10 atom% were intravenously injected. [ 2 H 5 ring]phenylalanine enrichments in the plasma-free phenylalanine and the albumin and fibrinogen isolates were measured by gas chromatography-mass spectrometry. Fractional Synthesis Rates of albumin were normal in Child A cirrhosis (7.6 ± 2.2%d), but were lower in both Child B (3.5 ± 0.8%d) and C (4.5 ± 2.8%d). Absolute Rates of albumin Synthesis were (103 ± 30 mg/kg/d) in the child A group and substantially lower in the Child B (50 ± 3 mg/kg/d) and C (36 ± 20 mg/kg/d) group. The average Fractional Synthesis Rate of fibrinogen was 16.7 ± 7.5%d and the absolute Synthesis Rate 11.6 ± 6.4 mg/kg/d. The values of the galactose elimination capacity and the aminopyrin breath test were below the normal range in all patients, gradually decreasing with an increase in the severity of the clinical stage of cirrhosis. Albumin Synthesis Rates significantly correlated with the Child scores, the galactose elimination capacity, and the aminopyrin breath test, whereas fibrinogen Synthesis Rates showed no such correlations. (Hepatology 1996 Jul;24(1):53-9)
