Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients

Lyons, Jeremy; Rauh-Pfeiffer, Astrid A. M.; Ming-Yu, Yong; Lu, Xiaoming; Zurakowski, David; Curley, Martha A. Q.; Collier, Sharon; Duggan, Christopher; Nurko, Samuel; Thompson, John; Ajami, Alfred M.; Borgonha, Sudhir; Young, Vernon R.; Castillo, Leticia

doi:10.1097/00003246-200104000-00036

Cited by 119 publications

(89 citation statements)

References 37 publications

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“…From 12 h onwards a mixture of stable isotope-labelled AA was infused into all animals as described previously (18) . Briefly, 1 g [U- 13 C]whole algal hydrolysate prepared from Celtone-C (Martek Biosciences Corporation), plus 100 mg L-[5-13 C]methyl methionine 100 mg, 120 mg L-[1-13 C]cysteine and 150 mg L- [2][3][4][5][6][7][8][9][10][11][12][13][14][15] N]glutamine (all sourced from Cambridge Isotope Laboratories), was dissolved in 100 ml of buffered physiological saline (pH 7·4) containing 50 000 IU of heparin and infused at 10 g/h. Methionine, cysteine and glutamine were added, as these AA are lost during the acid hydrolysis preparation of the whole algal powder.…”

Section: Main Studymentioning

confidence: 99%

Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs

et al. 2015

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Some effects of parasitism, endotoxaemia or sepsis can be mitigated by provision of extra protein. Supplemented protein may encompass a metabolic requirement for specific amino acids (AA). The current study investigates a method to identify and quantify the amounts of AA required during inflammation induced by an endotoxin challenge. One of each pair of six twin sheep was infused in the jugular vein for 20 h with either saline (control) or lipopolysaccharide (LPS, 2 ng/kg body weight per min) from Escherichia coli. Between 12 and 20 h a mixture of stable isotope-labelled AA was infused to measure irreversible loss rates. From 16 to 20 h all sheep were supplemented with a mixture of unlabelled AA infused intravenously. Blood samples were taken before the start of infusions, and then continuously over intervals between 14 and 20 h. At 20 h the sheep were euthanised, and liver and kidney samples were taken for measurement of serine-threonine dehydratase (SDH) activity. LPS infusion decreased plasma concentrations of most AA (P < 0·05; P < 0·10 for leucine and tryptophan), except for phenylalanine (which increased P = 0·022) and tyrosine. On the basis of the incremental response to the supplemental AA, arginine, aspartate, cysteine, glutamate, lysine (tendency only), glycine, methionine, proline, serine and threonine were important in the metabolic response to the endotoxaemia. The AA infusion between 16 and 20 h restored the plasma concentrations in the LPS-treated sheep for the majority of AA, except for glutamine, isoleucine, methionine, serine and valine. LPS treatment increased (P < 0·02) SDH activity in both liver and kidney. The approach allows quantification of key AA required during challenge situations.Key words: Endotoxin lipopolysaccharide: Amino acids: Irreversible loss rate: Serine-threonine dehydratase: SheepThe protein and amino acid (AA) demands of animals for normal physiological states (e.g. growth, pregnancy and lactation) are now well characterised, especially for pigs and poultry (1) and with progress made in ruminants (2) . These requirements are altered, however, in response to injury, infection and parasitic challenge. In many cases, impact of these challenges can be ameliorated and the rate of recovery improved by provision of additional protein in the diet (3)(4)(5)(6) . Often, however, the amount of protein required is not known, with consequences for both animal performance and farm economics.More importantly, protein per se may not be required, but instead the metabolic responses to the challenge may increase the demand for specific AA. For example, practical and theoretical arguments have been presented for additional arginine in cardiovascular and pulmonary disorders (7)(8)(9)(10) , for cysteine (11) , leucine (12) and threonine (13) in sepsis, for glutamine in endotoxaemia (10) , and for phenylalanine to support acutephase protein synthesis (14) . In other situations, combinations of AA have been proposed (10,15,16) . Obviously different stages of injury, infection or recover...

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Section: Main Studymentioning

confidence: 99%

Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs

et al. 2015

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“…However, we also demonstrate that increases in maternal oxidative stress with the onset of labor are significantly greater in women who will go on to have subsequent intrapartum fever develop. Although previous publications have reported on the association between increased oxidative stress and the severity of febrile illness, [21][22][23] to our knowledge this is the first report of increases in oxidative stress preceding clinical febrile morbidity. Our data cannot be used to determine whether the observed increases in oxidative stress are causative or occur in association with other factors that predispose to maternal fever.…”

Section: Commentmentioning

confidence: 55%

78: Maternal and fetal oxidative stress and intrapartum term fever

Goetzl¹,

Yefim²,

Roedner³

et al. 2009

American Journal of Obstetrics and Gynecology

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OBJECTIVE-The association between maternal chorioamnionitis and fetal oxidative stress has not been well established.STUDY DESIGN-A nested case control study was performed within a prospective cohort of term nulliparous women: 20 cases (intrapartum fever of >100.4°F) and 20 afebrile controls. Oxidative stress was assessed using ThioGlo-1 (TG-1; Calbiochem, San Diego, CA) fluorescent sulfhydryl detection. Median levels (± interquartile range) of protein-thiol sulfhydryls were compared.RESULTS-In early labor, maternal oxidative stress (lower protein sulfhydryls) was significantly higher in those women who subsequently had intrapartum fever develop (79.87 ± 22.88 vs 127.73 ± 43.79 counts/second per μg protein; P < .001). In contrast, cord serum sulfhydryls were not different between groups (75.77 ± 14.00 vs 75.04 ± 17.83 counts/second per μg protein; P = .99) CONCLUSION-Our data suggest that the term human fetus is protected from maternal oxidative stress associated with intrapartum fever. However, maternal oxidative status in early labor is associated with subsequent intrapartum fever. Optimal fetal neuroprotection will require a more precise knowledge of pathogenic mechanisms.Keywords fetal neuroprotection; fever; inflammation; intrapartum fever; oxidative stress Fetal exposure to chorioamnionitis (hyperthermia and inflammation) at term has long been accepted as a potent risk factor for neonatal encephalopathy and cerebral palsy. Chorioamnionitis accounts for between 11% and 22% of cases of cerebral palsy in near-term and term infants, and carries an odds ratio of 9.3 for otherwise unexplained cerebral palsy. 1,2 The current diagnosis of chorioamnionitis is largely based on maternal fever; fundal tenderness cannot be used after epidural analgesia and purulent vaginal discharge is a subjective finding. Maternal oral temperature is the best indicator of intrauterine temperature Presented orally at the 30th Annual Meeting, Society for Maternal-Fetal Medicine, Chicago, IL, Feb. 1-6, 2010. The racing flag logo above indicates that this article was rushed to press for the benefit of the scientific community.Reprints not available from the authors. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript but underestimates it by an average of 0.8°C. 3 In turn, fetal core temperature is approximately 0.75°C higher than fetal skin/intrauterine temperature. 4 Therefore, the widely used definition of intrapartum fever (38.0°C) is generally associated with fetal brain temperatures of 39.5°C or higher.Term infants have a low risk of neonatal encephalopathy of approximately 0.12%. 5 The observed risk of encephalopathy with fetal exposure to maternal fever alone is 1.13% and the risk with fetal exposure to acidosis (cord pH <7.05) alone is 1.58%. However, the combination of maternal fever and neonatal acidosis results in a substantial increase in the risk of neonatal encephalopathy to 12.5%, independent of neonatal sepsis. 5 This observation has led to the hypothesis that maternal fever ...

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“…However, the GSSG/GSH index (the reciprocal of thiol index) has been shown to be higher in whole blood of pediatric patients with septic shock [17]. It is possible that the expected higher ROS production in sepsis results in GSH consumption, but a lower GSH synthesis has also been observed during pediatric sepsis [5]. In our results, the lower concentration of GSH did not correlate with higher GSHPx activity; hence, this finding is probably secondary to non-enzymatic GSH consumption.…”

Section: Discussionmentioning

confidence: 99%

“…Available evidence in the adult population supports a major role of ROS production in the development of the systemic response occurring in sepsis and septic shock as well as its contribution to the progression toward MODS [3,4]. There are few studies regarding the occurrence of oxidative stress in pediatric sepsis after the neonatal period, which show conflicting results [5][6][7]. Overall, the behavior of oxidative stress biomarkers in pediatric sepsis pathophysiology and the role of oxidative stress as a potential therapeutic target have not been properly addressed.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress biomarkers in pediatric sepsis: a prospective observational pilot study

et al. 2016

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Objectives: Oxidative stress is known to participate in the progression of sepsis. Definite data regarding the behavior of oxidative stress biomarkers in pediatric sepsis is still lacking. This study hypothesized that oxidative stress occurs in pediatric sepsis and that the magnitude of the redox derangement is associated with worse clinical progression. Methods: Forty-two previously healthy pediatric patients with sepsis and a group of control subjects were included. Oxidative stress and inflammatory activity biomarkers were determined in blood samples. Patients were prospectively followed until their discharge or death. Results: Patients with non-severe and severe sepsis showed higher levels of plasmatic antioxidant capacity, lower erythrocyte thiol index, lower superoxide dismutase and catalase activities, higher glutathione peroxidase activity, and higher plasmatic F 2 -isoprostanes concentration than controls. Patients with severe sepsis had higher NF-kappaB activation than those with non-severe sepsis. Although we observed changes in some biomarkers in patients with worse clinical evolution, the explored biomarkers did not correlate with clinical estimators of outcome. Discussion: Oxidative stress occurs in pediatric sepsis, resulting in oxidative damage. The explored biomarkers are not useful as outcome predictors in the studied population. The behavior of these biomarkers still needs to be addressed in broader groups of pediatric patients with sepsis.

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Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients

Cited by 119 publications

References 37 publications

Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs

Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs

78: Maternal and fetal oxidative stress and intrapartum term fever

Oxidative stress biomarkers in pediatric sepsis: a prospective observational pilot study

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