Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-13T22:32:41.584Z Has data issue: false hasContentIssue false
  • English
  • Français

Impaired energy metabolism during neonatal sepsis: the effects of glutamine

Published online by Cambridge University Press:  05 March 2007

Simon Eaton
Simon Eaton*
Affiliation:
Surgery Unit and Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health (University College London), 30 Guilford Street, London WC1N1EHUK
*
Corresponding author: Dr S. Eaton, fax:+44 20 7404 6181, email s., [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Neonatal sepsis is an important cause of morbidity and mortality as a result of multiple organ system failure, particularly in neonates requiring total parenteral nutrition. Suitable therapies and support are needed both to prevent sepsis and to prevent multiple organ failure. After bacterial infection, pro-inflammatory cytokines trigger the antimicrobial activity of macrophages and neutrophils, resulting in production of reactive species such as H2O2, NO, superoxide and peroxynitrite. However, excess production can lead to host tissue damage. Incubation of either hepatocytes or heart mitochondria from neonatal rats with these reactive species, or with cytokines, leads to impairment of mitochondrial oxidative function, and in an animal model of neonatal sepsis similar results to the in vitro findings have been demonstrated. Recent in vivo studies, using indirect calorimetry of suckling rat pups, show that during endotoxaemia there is a profound hypometabolism, associated with hypothermia. Having determined that cellular oxidative function may be impaired during sepsis, it is of great importance to try to identify therapeutic measures. Much interest has been shown in glutamine, which may become essential during sepsis. It has been shown that hepatic glutamine is rapidly depleted during endotoxaemia. When hepatocytes from endotoxaemic rats were incubated with glutamine, there was a restoration of mitochondrial structure and metabolism. In vivo, intraperitoneal injection of glutamine into endotoxic suckling rats partially reversed hypometabolism, markedly reduced the incidence of hypothermia and improved clinical status. These results suggest that glutamine has a beneficial effect during sepsis in neonates.

Keywords

Neonatal sepsisEnergy metabolismGlutamineTherapeutic strategies
Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 62 , Issue 3 , August 2003 , pp. 745 - 751
Copyright
Copyright © The Nutrition Society 2003

References

Anderson, ME, Powrie, F, Puri, RN & Meister, A (1985) Glutathione monoethyl ester: preparation, uptake by tissues, and conversion to glutathione. Archives of Biochemistry and Biophysics 239, 538–548.CrossRefGoogle ScholarPubMed
Anderson, MR & Blumer, JL (1997) Advances in the therapy for sepsis in children. Pediatric Clinics of North America 44, 179–205.CrossRefGoogle ScholarPubMed
Andersson, S, Pitkanen, O & Hallman, M, (1992) Parenteral lipids and free-radicals in preterm infants. Archives of Disease in Childhood 67, 152.CrossRefGoogle ScholarPubMed
Ardawi, MS (1992) Hepatic glutamine metabolism in the septic rat. Clinical Science 82, 709–716.Google Scholar
Ardawi, MS & Newsholme, EA (1990) Glutamine, the immune system, and the intestine. Journal of Laboratory and Clinical Medicine 115, 654–655Google ScholarPubMed
Arndt, P & Abraham, E (2001) Immunological therapy of sepsis: experimental therapies. Intensive Care Medicine 27, S104–S115.CrossRefGoogle ScholarPubMed
Avanoglu, A, Ergun, O, Bakirtas, F & Erdener, A (1997) Characteristics of multisystem organ failure in neonates. European Journal of Pediatric Surgery 7, 263–266.CrossRefGoogle ScholarPubMed
Babu, R, Eaton, S, Drake, DP, Spitz, L & Pierro, A (2001) Glutamine and glutathione counteract the inhibitory effects of mediators of sepsis in neonatal hepatocytes. Journal of Pediatric Surgery 36, 282–286.CrossRefGoogle ScholarPubMed
Barreiro, E, Comtois, AS, Gea, J, Laubach, VE & Hussain, SNA (2002) Protein tyrosine nitration in the ventilatory muscles – Role of nitric oxide synthases. American Journal of Respiratory Cell and Molecular Biology 26, 438–446.CrossRefGoogle ScholarPubMed
Basu, R, Muller, DPR, Drury, JA, Cooke, RWI, Eaton, S & Pierro, A (2000) Intravenous medium-chain triacylglycerol administration is associated with increased free radical activity. Proceedings of the Nutrition Society 59 165A.Google Scholar
Basu, R, Muller, DPR, Eaton, S, Merryweather, I & Pierro, A (1999a) Lipid peroxidation can be reduced in infants on total parenteral nutrition by promoting fat utilisation. Journal of Pediatric Surgery 34, 255–259.CrossRefGoogle ScholarPubMed
Basu, R, Muller, DPR, Papp, E, Merryweather, I, Eaton, S, Klein, N & Pierro, A (1999b) Free radical formation in infants: the effect of critical illness, parenteral nutrition, and enteral feeding. Journal of Pediatric Surgery 34, 1091–1095.CrossRefGoogle ScholarPubMed
Beale, RJ, Bryg, DJ & Bihari, DJ (1999) Immunonutrition in the critically ill: A systematic review of clinical outcome. Critical Care Medicine 27, 2799–2805.CrossRefGoogle ScholarPubMed
Beckman, JS & Koppenol, WH (1996) Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and the ugly. American Journal of Physiology 40, C1424–C1437.CrossRefGoogle Scholar
Bernard, GR, Vincent, JL, Laterre, PF, LaRosa, SP, Dhainaut, JF, Lopez-Rodriguez, A, Steingrub, JS, Garber, GE, Helterbrand, JD, Ely, EW & Fisher, CJ Jr (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. New England Journal of Medicine 344, 699–709.CrossRefGoogle ScholarPubMed
Bolanos, JP, Heales, SJR, Peuchen, S, Barker, JE, Land, JM & Clark, JB (1996) Nitric oxide-mediated mitochondrial damage: A potential neuroprotective role for glutathione. Free Radical Biology and Medicine 21, 995–1001.CrossRefGoogle Scholar
Borutaite, V & Brown, GC (1996) Rapid reduction of nitric oxide by mitochondria, and reversible inhibition of mitochondrial respiration by nitric oxide. Biochemical Journal 315, 295–299.CrossRefGoogle ScholarPubMed
Brealey, D, Brand, M, Hargreaves, I, Heales, S, Land, J, Smolenski, R, Davies, NA, Cooper, CE & Singer, M (2002) Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360, 219–223.CrossRefGoogle ScholarPubMed
Briassoulis, G, Venkataraman, S & Thompson, AE (2000) Energy expenditure in critically ill children. Critical Care Medicine 28, 1166–1172.CrossRefGoogle ScholarPubMed
Chwals, WJ, Lally, KP, Woolley, MM, Mahour, GH (1988) Measured energy expenditure in critically ill infants and young children. Journal of Surgical Research 44, 467–472.CrossRefGoogle ScholarPubMed
Clementi, E, Brown, GC, Feelisch, M & Moncada, S (1998) Persistent inhibition of cell respiration by nitric oxide: Crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proceedings of the National Academy of Sciences USA 95, 7631–7636.CrossRefGoogle ScholarPubMed
Coss-Bu, JA, Klish, WJ, Walding, D, Stein, F, Smith, EO & Jefferson, LS (2001) Energy metabolism, nitrogen balance, and substrate utilization in critically ill children. American Journal of Clinical Nutrition 74, 664–669.CrossRefGoogle ScholarPubMed
Cuthbertson, DP (1945) Post-shock metabolic response. Lancet i, 433–437.Google Scholar
Cuzzocrea, S, Mazzon, E, Dugo, L, Caputi, AP, Aston, K, Riley, DP & Salvemini, D (2001) Protective effects of a new stable, highly active SOD mimetic, M40401 in splanchnic artery occlusion and reperfusion. British Journal of Pharmacology 132, 19–29.CrossRefGoogle ScholarPubMed
Cuzzocrea, S, Misko, TP, Costantino, G, Mazzon, E, Micali, A, Caputi, AP, MacArthur, H & Salvemini, D (2000) Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion. FASEB Journal 14, 1061–1072.CrossRefGoogle Scholar
Davis, CA, Nick, HS & Agarwal, A (2001) Manganese superoxide dismutase attenuates cisplatin-induced renal injury: Importance of superoxide. Journal of the American Society of Nephrology 12, 2683–2690.CrossRefGoogle ScholarPubMed
Deitch, EA (1992) Multiple organ failure – pathophysiology and potential future therapy. Annals of Surgery 216, 117–134.CrossRefGoogle ScholarPubMed
Donnell, SC, Lloyd, DA, Eaton, S & Pierro, A (2002) The metabolic response to intravenous medium-chain triglycerides in surgical infants. Journal of Pediatrics 141, 689–694.CrossRefGoogle Scholar
Eaton, S (2002) Control of mitochondrial β-oxidation flux. Progress in Lipid Research 41, 197–239.CrossRefGoogle ScholarPubMed
Eaton, S, Bartlett, K & Quant, PA (2001) Carnitine palmitoyl transferase I and the control of β-oxidation in heart mitochondria. Biochemical and Biophysical Research Communications 285, 537–539.CrossRefGoogle ScholarPubMed
Ewart, HS, Quian, D, Brosnan, JT, (1995) Activation of hepatic glutaminase in the endotoxin-treated rat. Journal of Surgical Research 59, 245–249.CrossRefGoogle ScholarPubMed
Fanaroff, AA, Korones, SB, Wright, LL, Verter, J, Poland, RL, Bauer, CR, Tyson, JE, Philips, JB, Edwards, W, Lucey, JF, Catz, CS, Shankaran, S & Oh, W, (1998) Incidence, presenting features risk factors and significance of late onset septicemia in very low birth weight infants. Pediatric Infectious Disease Journal 17, 593–598.CrossRefGoogle ScholarPubMed
Ford, HR & Rowe, MI (1998) Sepsis and related considerations. In Pediatric Surgery, 135–155 [O'Neill, JA Rowe, MI, Gorsfeld, JL]. St Louis, MO: Mosby-Year Book IncGoogle Scholar
Friedman, G, Silva, E & Vincent, JL (1998) Has the mortality of septic shock changed with time?. Critical Care Medicine 26, 2078–2086.CrossRefGoogle ScholarPubMed
Fukumoto, K, Eaton, S, Spitz, L & Pierro, A (2003a) Cardiac and renal mitochondria respond differently to mediators of sepsis in neonates. Journal of Surgical ResearchCrossRefGoogle Scholar
Fukumoto, K, Pierro, A, Spitz, L & Eaton, S (2002a) Differential effects of neonatal endotoxemia on heart and kidney carnitine palmitoyl transferase I. Journal of Pediatric Surgery 37, 723–726.CrossRefGoogle ScholarPubMed
Fukumoto, K, Pierro, A, Spitz, L & Eaton, S (2002b) Endotoxaemia increases muscle-carnitine palmitoyl transferase I tyrosine nitration. Journal of Molecular and Cellular Cardiology 34 A24.CrossRefGoogle Scholar
Fukumoto, K, Pierro, A, Spitz, L & Eaton, S (2003b) Neonatal endotoxaemia affects heart but not kidney bioenergetics. Journal of Pediatric Surgery 38, 690–693.CrossRefGoogle Scholar
Garrett-Cox, RG, Pierro, A, Spitz, L & Eaton, S (2003) Body temperature and heat production in suckling rat endotoxaemia: beneficial effects of glutamine. Journal of Pediatric Surgery 38, 37–43.CrossRefGoogle ScholarPubMed
Gellerich, FN, Trumbeckaite, S, Hertel, K, Zierz, S, MullerWerdan, U, Werdan, K, Redl, H & Schlag, G (1999) Impaired energy metabolism in hearts of septic baboons: Diminished activities of Complex I & Complex II of the mitochondrial respiratory chain. Shock 11, 336–341.CrossRefGoogle ScholarPubMed
Girard, J Ferré, P, Pégorier, J-P & Duee, PH (1992) Adaptations of glucose and fatty-acid metabolism during perinatal-period and suckling-weaning transition. Physiological Reviews 72, 507–562.CrossRefGoogle ScholarPubMed
Grattagliano, I, Vendemiale, G & Lauterburg, BH (1999) Reperfusion injury of the liver: role of mitochondria and protection by glutathione ester. Journal of Surgical Research 86, 2–8.CrossRefGoogle ScholarPubMed
Grimble, RF (2001) Nutritional modulation of immune function. Proceedings of the Nutrition Society 60, 389–397.CrossRefGoogle ScholarPubMed
Grinnell, BW Joyce, D (2001) Recombinant human activated protein C: a system modulator of vascular function for treatment of severe sepsis. Critical Care Medicine 29, S53–S60.CrossRefGoogle ScholarPubMed
Hammarqvist, F, Wernerman, J, Ali, R, von der Decken, A & Vinnars, E, (1989) Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance. Annals of Surgery 209, 455–461.CrossRefGoogle ScholarPubMed
Haussinger, D (1998) Hepatic glutamine transport and metabolism. Advances in Enzymology and Related Areas of Molecular Biology 72, 43–86.Google ScholarPubMed
Heyland, DK, Novak, F, Drover, JW, Jain, A, Su, XY & Suchner, U (2001) Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. Journal of the American Medical Association 286, 944–953.CrossRefGoogle ScholarPubMed
Jaksic, T, Shew, SB, Keshen, TH, Dzakovic, A & Jahoor, F (2001) Do critically ill surgical neonates have increased energy expenditure?. Journal of Pediatric Surgery 36, 63–67.CrossRefGoogle ScholarPubMed
Janero, DR & Hreniuk, D (1996) Suppression of TCA cycle activity in the cardiac muscle cell by hydroperoxide-induced oxidant stress. American Journal of Physiology 39, C1735–C1742.CrossRefGoogle Scholar
Jones, M, Pierro, A, Hammond, P & Lloyd, D (1993) The metabolic response to operative stress in infants. Journal of Pediatric Surgery 28, 1258–1263.CrossRefGoogle ScholarPubMed
Jones, M, Pierro, A, Hammond, P & Lloyd, D (1995) The effect of major operations on heart-rate, respiratory rate, physical-activity, temperature and respiratory gas-exchange in infants. European Journal of Pediatric Surgery 5, 9–12.CrossRefGoogle ScholarPubMed
Jones, MO, Pierro, A, Hashim, IA, Shenkin, A & Lloyd, DA (1994) Postoperative changes in resting energy-expenditure and interleukin-6 level in infants. British Journal of Surgery 81, 536–538.CrossRefGoogle ScholarPubMed
Kang, YH, Falk, MC, Bentley, TB & Lee, CH (1995) Distribution and role of lipopolysaccharide in the pathogenesis of acute renal proximal tubule injury. Shock 4, 441–449.Google ScholarPubMed
Kantrow, SP, Taylor, DE, Carraway, MS & Piantadosi, CA (1997) Oxidative metabolism in rat hepatocytes and mitochondria during sepsis. Archives of Biochemistry and Biophysics 345, 278–288.CrossRefGoogle ScholarPubMed
Karbowski, M, Kurono, C, Nishizawa, Y, Horie, Y, Soji, T & Wakabayashi, T (1997) Induction of megamitochondria by some chemicals inducing oxidative stress in primary cultured rat hepatocytes. Biochimica et Biophysica Acta 1349, 242–250.CrossRefGoogle ScholarPubMed
Kim, SC, Pierro, A, Zamparelli, M, Spitz, L & Eaton, S (2002) Fatty acid oxidation in neonatal hepatocytes: Effects of sepsis and glutamine. Nutrition 18, 298–300.CrossRefGoogle ScholarPubMed
Kooy, NW, Lewis, SJ Royall, JA, Ye, YZ, Kelly, DR & Beckman, JS (1997) Extensive tyrosine nitration in human myocardial inflammation: Evidence for the presence of peroxynitrite. Critical Care Medicine 25, 812–819.CrossRefGoogle ScholarPubMed
Lacey, JM, Crouch, JB, Benfell, K, Ringer, SA, Wilmore, CK, Maguire, D & Wilmore, DW (1996) The effects of glutamine-supplemented parenteral nutrition in premature infants. Journal of Parenteral and Enteral Nutrition 20, 74–80.CrossRefGoogle ScholarPubMed
Lacey, JM & Wilmore, DW (1990) Is glutamine a conditionally essential amino acid?. Nutrition Reviews 48, 297–309.CrossRefGoogle ScholarPubMed
Lanza-Jacoby, S, Sedkova, N, Phetteplace, H & Perrotti, D (1997) Sepsis-induced regulation of lipoprotein lipase expression in rat adipose tissue and soleus muscle. Journal of Lipid Research 38, 701–710.CrossRefGoogle ScholarPubMed
Liao, W, Rudling, M & Angelin, B (1996) Endotoxin suppresses rat hepatic low-density lipoprotein receptor expression. Biochemical Journal 313, 873–878.CrossRefGoogle ScholarPubMed
Lionetti, L, Iossa, S, Liverini, G & Brand, MD (1998) Changes in the hepatic mitochondrial respiratory system in the transition from weaning to adulthood in rats. Archives of Biochemistry and Biophysics 352, 240–246.CrossRefGoogle ScholarPubMed
McAndrew, HF, Lloyd, DA, Rintala, R & Van Saene, HK (1999) Intravenous glutamine or short-chain fatty acids reduce central venous catheter infection in a model of total parenteral nutrition. Journal of Pediatric Surgery 34, 281–285.CrossRefGoogle ScholarPubMed
Marcondes, S, Turko, IV & Murad, F (2001) Nitration of succinyl-CoA:3-oxoacid CoA-transferase in rats after endotoxin administration. Proceedings of the National Academy of Sciences USA 98, 7146–7151.CrossRefGoogle ScholarPubMed
Markley, MA, Pierro, A & Eaton, S (2002) Hepatocyte mitochondrial metabolism is inhibited in neonatal rat endotoxaemia: effects of glutamine. Clinical Science 102, 337–344.CrossRefGoogle ScholarPubMed
Mehr, SS, Sadowsky, JL, Doyle, LW & Carr, J (2002) Sepsis in neonatal intensive care in the late 1990s. Journal of Paediatrics And Child Health 38, 246–251.CrossRefGoogle ScholarPubMed
Memon, RA, Fuller, J, Moser, AH, Smith, PJ, Feingold, KR & Grunfeld, C (1998) In vivo regulation of acyl-CoA synthetase mRNA and activity by endotoxin and cytokines. American Journal of Physiology 38, E64–E72.Google Scholar
Messner, UK, Briner, VA & Pfeilschifter, J (1999) Tumor necrosis factor-alpha and lipopolysaccharide induce apoptotic cell death in bovine glomerular endothelial cells. Kidney International 55, 2322–2337.CrossRefGoogle Scholar
Mizock, BA (2001) Alterations in fuel metabolism in critical illness: hyperglycaemia. Best Practice and Research Clinical Endocrinology and Metabolism 15, 533–551.CrossRefGoogle ScholarPubMed
Moberly, JB, Logan, J, Borum, PR, Story, KO, Webb, LE, Jassal, SV, Mupas, L, Rodela, H, Alghamdi, GA, Moran, JE, Wolfson, M, Martis, L & Oreopoulos, DG (1998) Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine(R)). Journal of the American Society of Nephrology 9, 1093–1099.CrossRefGoogle Scholar
Monk, DN, Plank, LD, Franch-Arcas, G, Finn, PJ, Streat, SJ & Hill, GL (1996) Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt trauma. Annals of Surgery 223, 395–405.CrossRefGoogle ScholarPubMed
Morecroft, JA, Spitz, L, Hamilton, PA & Holmes, SJK (1994) Necrotizing enterocolitis – multisystem organ failure of the newborn. Acta Paediatrica 83, 21–23.CrossRefGoogle Scholar
New, KJ, Eaton, S, Elliott, KRF, Spitz, L & Quant, PA (2001) Effect of lipopolysaccharide and cytokines on oxidative metabolism in neonatal rat hepatocytes. Journal of Pediatric Surgery 36, 338–340.CrossRefGoogle ScholarPubMed
Nordenstrom, J, Carpentier, YA, Askanazi, J, Robin, AP, Elwyn, DH, Hensle, TW & Kinney, JM (1983) Free fatty-acid mobilization and oxidation during total parenteral-nutrition in trauma and infection. Annals of Surgery 198, 725–735.CrossRefGoogle ScholarPubMed
Nulton-Persson, AC & Szweda, LI (2001) Modulation of mitochondrial function by hydrogen peroxide. Journal of Biological Chemistry 276, 23357–23361.CrossRefGoogle ScholarPubMed
Okada, Y, Klein, NJ, Van Saene, HK, Webb, G, Holzel, H & Pierro, A (2000) Bactericidal activity against coagulase-negative staphylococci is impaired in infants receiving long-term parenteral nutrition. Annals of Surgery 231, 276–281.CrossRefGoogle ScholarPubMed
Phillips, R, Ott, L, Young, B & Walsh, J (1987) Nutritional support and measured energy expenditure of the child and adolescent with head injury. Journal of Neurosurgery 67, 846–851.CrossRefGoogle ScholarPubMed
Picard, F, Kapur, S, Perreault, M, Marette, A & Deshaies, Y (2001) Nitric oxide mediates endotoxin-induced hypertriglyceridemia through its action on skeletal muscle lipoprotein lipase. FASEB Journal 15, U5–U23.CrossRefGoogle ScholarPubMed
Pierro, A, Carnielli, V, Filler, RM, Smith, J & Heim, T (1989) Metabolism of intravenous fat emulsion in the surgical newborn. Journal of Pediatric Surgery 24, 95–92.CrossRefGoogle ScholarPubMed
Pierro, A, Van Saene, HKF, Donnell, SC, Hughes, J, Ewan, C, Nunn, AJ & Lloyd, DA (1996) Microbial translocation in neonates and infants receiving long-term parenteral-nutrition. Archives of Surgery 131, 176–179.CrossRefGoogle ScholarPubMed
Pierro, A, Van Saene, HKF, Jones, MO, Brown, D, Nunn, AJ & Lloyd, DA (1998) Clinical impact of abnormal gut flora in infants receiving parenteral nutrition. Annals of Surgery 227, 547–552.CrossRefGoogle ScholarPubMed
Pitkanen, O (1992) Peroxidation of lipid emulsions – a hazard for the premature-infant receiving parenteral-nutrition. Free Radical Biology and Medicine 13, 239–245.CrossRefGoogle ScholarPubMed
Pitkanen, O, Hallman, M & Andersson, S (1991) Generation of free-radicals in lipid emulsion used in parenteral-nutrition. Pediatric Research 29, 56–59.CrossRefGoogle ScholarPubMed
Plank, LD, Connolly, AB & Hill, GL (1998) Sequential changes in the metabolic response in severely septic patients during the first 23 days after the onset of peritonitis. Annals of Surgery 228, 146–158.CrossRefGoogle ScholarPubMed
Poon, BY, Goddard, CM, Leaf, CD, Russell, JA & Walley, KR (1998) L -2-oxothiazolidine-4-carboxylic acid prevents endotoxininduced cardiac dysfunction. American Journal of Respiratory and Critical Care Medicine 158, 1109–1113.CrossRefGoogle ScholarPubMed
Riobo, NA, Clementi, E, Melani, M, Boveris, A, Cadenas, E, Moncada, S & Poderoso, JJ (2001) Nitric oxide inhibits mitochondrial NADH: ubiquinone reductase activity through peroxynitrite formation. Biochemical Journal 359, 139–145.CrossRefGoogle ScholarPubMed
Robin, AP, Askanazi, J, Greenwood, MRC, Carpentier, YA, Gump, FE & Kinney, JM (1981) Lipoprotein-lipase activity in surgical patients – influence of trauma and infection. Surgery 90, 401–408.Google ScholarPubMed
Romeo, C, Eaton, S, Quant, PA, Spitz, L & Pierro, A (1999) Neonatal oxidative liver metabolism: Effects of hydrogen peroxide, a putative mediator of septic damage. Journal of Pediatric Surgery 34, 1107–1111.CrossRefGoogle ScholarPubMed
Romeo, C, Eaton, S, Spitz, L & Pierro, A (2000) Nitric oxide inhibits neonatal hepatocyte oxidative metabolism. Journal of Pediatric Surgery 35, 44–48.CrossRefGoogle ScholarPubMed
Salvemini, D, Riley, DP, Lennon, PJ, Wang, ZQ, Currie, MG, MacArthur, H & Misko, TP (1999) Protective effects of a superoxide dismutase mimetic and peroxynitrite decomposition catalysts in endotoxin-induced intestinal damage. British Journal of Pharmacology 127, 685–692.CrossRefGoogle ScholarPubMed
Salvemini, D, Wang, ZQ, Stern, MK, Currie, MG & Misko, TP (1998) Peroxynitrite decomposition catalysts: Therapeutics for peroxynitrite-mediated pathology. Proceedings of the National Academy of Sciences USA 95, 2659–2663.CrossRefGoogle ScholarPubMed
Samra, JS, Summers, LKM & Frayn, KN (1996) Sepsis and fat metabolism. British Journal of Surgery 83, 1186–1196.Google ScholarPubMed
Sen, CK (1997) Nutritional biochemistry of cellular glutathione. Journal of Nutritional Biochemistry 8, 660–672.CrossRefGoogle Scholar
Smith, SD, Tagge, EP, Hannakan, C & Rowe, MI (1991) Characterization of neonatal multisystem organ failure in the surgical newborn. Journal of Pediatric Surgery 26, 494–499.CrossRefGoogle ScholarPubMed
Souba, WW & Austgen, TR (2001) Interorgan glutamine flow following surgery and infection. Journal of Parenteral and Enteral Nutrition 14, 90S–93S.Google Scholar
Souba, WW, Klimberg, VS, Hautamaki, RD, Mendenhall, WH, Bova, FC, Howard, RJ, Bland, KI & Copeland, EM (1990) Oral glutamine reduces bacterial translocation following abdominal radiation. Journal of Surgical Research 48, 1–5.CrossRefGoogle ScholarPubMed
Stehle, P, Zander, J, Mertes, N, Albers, S, Puchstein, C, Lawin, P & Fürst, P (1989) Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet i, 231–233.CrossRefGoogle Scholar
Stoll, BJ, Holman, RC & Schuchat, A (1998) Decline in sepsis-associated neonatal and infant deaths in the United States, 1979 through 1994. Pediatrics 102, E181–E187.CrossRefGoogle ScholarPubMed
Tilden, SJ, Watkins, S, Tong, TK & Jeevanandam, M (1989) Measured energy-expenditure in pediatric intensive-care patients. American Journal of Diseases of Children 143, 490–492.Google ScholarPubMed
Trumbeckaite, S, Opalka, JR, Neuhof, C, Zierz, S & Gellerich, FN (2001) Different sensitivity of rabbit heart and skeletal muscle to endotoxin-induced impairment of mitochondrial function. European Journal of Biochemistry 268, 1422–1429.CrossRefGoogle ScholarPubMed
Turi, RA, Petros, A, Eaton, S, Fasoli, L, Powis, M, Basu, R & Pierro, A (2001) Energy metabolism of infants and children with systemic inflammatory response syndrome and sepsis. Annals of Surgery 233, 581–587.CrossRefGoogle ScholarPubMed
Valcarce, C, Navarrete, R, Encabo, P, Loeches, E, Satrustegui, J & Cuezva, J (1988) Postnatal-development of rat-liver mitochondrial functions – the roles of protein-synthesis and of adenine-nucleotides. Journal of Biological Chemistry 263, 7767–7775.CrossRefGoogle ScholarPubMed
Vejchapipat, P, Eaton, S, Fukumoto, K, Parkes, HG, Spitz, L & Pierro, A (2002) Hepatic glutamine metabolism during endotoxemia in neonatal rats. Nutrition 18, 293–297.CrossRefGoogle ScholarPubMed
Vlessis, AA, Goldman, RK & Trunkey, DD (1995) New concepts in the pathophysiology of oxygen-metabolism during sepsis. British Journal of Surgery 82, 870–876.CrossRefGoogle ScholarPubMed
White, MS, Shepherd, RW & McEniery, JA (2000) Energy expenditure in 100 ventilated, critically ill children: Improving the accuracy of predictive equations. Critical Care Medicine 28, 2307–2312.CrossRefGoogle ScholarPubMed
Wispe, JR, Bell, EF & Roberts, RJ (1985) Assessment of lipid peroxidation in newborn infants and rabbits by measurements of expired ethane and pentane: influence of parenteral lipid infusion. Pediatric Research 19, 374–379.CrossRefGoogle ScholarPubMed
Wolfe, RR (1997) Substrate utilization insulin resistance in sepsis/trauma. Baillieres Clinical Endocrinology And Metabolism 11, 645–657.CrossRefGoogle ScholarPubMed
Wolfe, RR & Martini, WZ (2000) Changes in intermediary metabolism in severe surgical illness. World Journal of Surgery 24, 639–647.CrossRefGoogle ScholarPubMed
Wolfe, RR, Shaw, JHF & Durkot, MJ (1985) Effect of sepsis on VLDL kinetics – responses in basal state and during glucose-infusion. American Journal of Physiology 248, E732–E740.Google ScholarPubMed