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Molecular Biology in the Pediatric Intensive Care Unit

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References

  1. Vincent JL, Abraham E. The last 100 years of sepsis. Am J Respir Crit Care Med 2006;173(3):256–263.

    PubMed  Google Scholar 

  2. Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med 2003;167(5):695–701.

    PubMed  Google Scholar 

  3. Statler KD, Jenkins LW, Dixon CE, Clark RS, Marion DW, Kochanek P. The simple model versus the super model: translating experimental traumatic brain injury research to the bedside. J Neurotrauma 2001;18:1195–1206.

    PubMed  CAS  Google Scholar 

  4. Prins ML, Hovda DA. Developing experimental models to address traumatic brain injury in children. J Neurotrauma 2003;20:123–137.

    PubMed  Google Scholar 

  5. Kochanek P, Clark RSB, Ruppel RA, Adelson PD, Bell MJ, Whalen MJ, et al. Biochemical, cellular and molecular mechanisms in the evolution of secondary damage after severe TBI in infants and children. Lessons learned from the bedside. Pediatr Crit Care 2000;1:4–19.

    Google Scholar 

  6. Ito J, Marmarou A, Barzo P, Fatouros P, Corwin F. Characterization of edema by diffusion-weighted imaging in experimental traumatic brain injury. J Neurosurg 1996;84(1):97–103.

    PubMed  CAS  Google Scholar 

  7. Graham DI, Adams JH, Doyle D. Ischaemic brain damage in fatal non-missile head injuries. J Neurol Sci 1978;39(2–3):213–234.

    PubMed  CAS  Google Scholar 

  8. Bouma GJ, Muizelaar JP, Stringer WA, Choi SC, Fatouros P, Young HF. Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg 1992;77:360–368.

    PubMed  CAS  Google Scholar 

  9. Obrist WD, Langfitt TW, Jaggi JL, Cruz J, Gennarelli TA. Cerebral blood flow and metabolism in comatose patients with acute head injury. Relationship to intracranial hypertension. J Neurosurg 1984;61:241–253.

    PubMed  CAS  Google Scholar 

  10. Schroder ML, Muizelaar JP, Bullock MR, Salvant JB, Povlishock JT. Focal ischemia due to traumatic contusions documented by stable xenon–CT and ultrastructural studies. J Neurosurg 1995;82:966–971.

    PubMed  CAS  Google Scholar 

  11. Enriquez P, Bullock R. Molecular and cellular mechanisms in the pathophysiology of severe head injury. Curr Pharm Design 2004;10:2131–2143.

    CAS  Google Scholar 

  12. Bullock R, Zauner A, Woodward JJ, Myseros J, Choi SC, Ward JD. Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg 1998;89:507–518.

    PubMed  CAS  Google Scholar 

  13. Adelson PD, Dixon CE, Robichaud P, Kochanek P. Motor and cognitive functional deficits following diffuse traumatic brain injury in the immature rat. J Neurotrauma 1997;14:99–108.

    PubMed  CAS  Google Scholar 

  14. Thomale UW, Schaser K, Kroppenstedt SN, Unterberg AW, Stover JF. Cortical hypoperfusion precedes hyperperfusion following controlled cortical impact injury. Acta Neurochir Suppl 2002;81:229–231.

    PubMed  CAS  Google Scholar 

  15. Leker RR, Shohami E. Cerebral ischemia and trauma-different etiologies yet similar mechanisms: neuroprotective opportunities. Brain Res Brain Res Rev 2002;39:55–73.

    PubMed  Google Scholar 

  16. Cherian L, Hlatky R, Robertson CS. Nitric oxide in traumatic brain injury. Brain Pathol 2004;14(2):195–201.

    PubMed  CAS  Google Scholar 

  17. Andresen J, Shafi NI, Bryan RM. Endothelial influences on cerebrovascular tone. J Appl Physiol 2006;100:318–327.

    PubMed  CAS  Google Scholar 

  18. Hillered L, Vespa PM, Hovda DA. Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis. J Neurotrauma 2005;22:3–41.

    PubMed  Google Scholar 

  19. Cherian L, Goodman JC, Robertson CS. Brain nitric oxide changes after controlled cortical impact injury in rats. J Neurophysiol 2000;83:2171–2178.

    PubMed  CAS  Google Scholar 

  20. Ahn MJ, Sherwood ER, Prough DS, Lin CY, DeWitt DS. The effects of traumatic brain injury on cerebral blood flow and brain tissue nitric oxide levels and cytokine expression. J Neurotrauma 2004;21:1431–1442.

    PubMed  Google Scholar 

  21. Cherian L, Chacko G, Goodman C, Robertson CS. Neuroprotective effects of L-arginine administration after cortical impact injury in rats: dose–response and time window. J Pharmacol Exp Ther 2003;304:617–623.

    PubMed  CAS  Google Scholar 

  22. Cherian L, Robertson CS. L-arginine and free radical scavengers increase cerebral blood flow and brain tissue nitric oxide concentrations after controlled cortical impact injury in rats. J Neurotrauma 2003;20:77–85.

    PubMed  Google Scholar 

  23. Dewitt DS, Smith TG, Deyo DJ. L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion after fluid-percussion TBI. J Neurotrauma 1997;14:223–233.

    PubMed  CAS  Google Scholar 

  24. Mendez DR, Cherian L, Robertson CS. Laser Doppler flow and brain tissue PO2 after cortical impact injury complicated by secondary ischemia in rats treated with arginine. J Trauma 2004;57:244–250.

    PubMed  Google Scholar 

  25. Bayir H, Kagan VE, Tyurina YY, Tyurin V, Ruppel RA, Adelson PD. Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatr Res 2002;51:571–578.

    PubMed  Google Scholar 

  26. Bayir H, Kagan V, Borisenko GG, Tyurina YY, Janesko KL, Vagni VA, et al. Enhanced oxidative stress in iNOS-deficient mice after traumatic brain injury: support for a neuroprotective role of iNOS. J Cereb Blood Flow Metab 2005;25:673–684.

    PubMed  CAS  Google Scholar 

  27. Wada K, Chatzipanteli K, Kraydieh S, Busto R, Dietrich WD. Inducible nitric oxide synthase expression after traumatic brain injury and neuroprotection with aminoguanidine treatment in rats. Neurosurgery 1998;43(6):1427–1436.

    PubMed  CAS  Google Scholar 

  28. Orihara Y, Ikematsu K, Tsuda R, Nakasono I. Induction of nitric oxide synthase by traumatic brain injury. Forensic Sci Int 2001;123(2–3):142–149.

    PubMed  CAS  Google Scholar 

  29. Louin G, Marchand-Verreccia C, Palmier B, Plotkine M, Jafarian-Tehrani M. Selective inhibition of inducible nitric oxide synthase reduces neurological deficit but not cerebral edema following traumatic brain injury. Neuropharmacology 2006;50(2):182–190.

    PubMed  CAS  Google Scholar 

  30. Jafarian-Tehrni M, Louin G, Royo NC, Besson VC, Bohme GA, Plotkine M, et al. 1400W, a potent selective inducible NOS inhibitor, improves histopathological outcome following traumatic brain injury in rats. Nitric Oxide 2005;12:61–69.

    Google Scholar 

  31. Jones NC, Constantin D, Gibson CL, Prior MJ, Morris PG, Marsden CA, et al. A detrimental role for nitric oxide synthase-2 in the pathology resulting from acute cerebral injury. J Neuropathol Exp Neurol 2004;63:708–720.

    PubMed  CAS  Google Scholar 

  32. Sinz EH, P K, Dixon CE, Clark RS, Carcillo JA, Schiding JK, et al. Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice. J Clin Invest 1999;104:647–656.

    PubMed  CAS  Google Scholar 

  33. Clark RS, P K, Obrist WD, Wong HR, Billiar TR, Wisniewski SR, et al. Cerebrospinal fluid and plasma nitrite and nitrate con-centrations after head injury in humans. Crit Care Med 1996;24:1243–1251.

    PubMed  CAS  Google Scholar 

  34. Bayir H, Kochanek P, Liu SX, Arroyo A, Osipov A, Jiang J, et al. Increased S-nitrosothiols and S-nitrosoalbumin in cerebrospinal fluid after severe traumatic brain injury in infants and children: indirect association with intracranial pressure. J Cereb Blood Flow Metab 2003;23:51–61.

    PubMed  CAS  Google Scholar 

  35. Armstead WM. Endothelins and the role of endothelin antagonists in the management of posttraumatic vasospasm. Curr Pharm Design 2004;10:2185–2192.

    CAS  Google Scholar 

  36. Provencio JJ, Vora N. Subarachnoid hemorrhage and inflammation: bench to bedside and back. Semin Neurol 2005;25(4):435–444.

    PubMed  Google Scholar 

  37. Petrov T, Rafols JA. Acute alterations of endothelin-1 and iNOS expression and control of the brain microcirculation after head trauma. Neurol Res 2001;23:139–143.

    PubMed  CAS  Google Scholar 

  38. Kasemri T, Armstead WM. Endothelin impairs ATP-sensitive K+ channel function after brain injury. Am J Physiol 1997;273:H2639–H2647.

    Google Scholar 

  39. Zubkov A, Miao L, Zhang J. Signal transduction of ET-1 in contraction of cerebral arteries. J Cardiovasc Pharmacol 2004;44:24–26.

    Google Scholar 

  40. Barone FC, Ohlstein EH, Hunter AJ, Campbell CA, Hadingham SH, Parsons AA. Selective antagonism of endothelin A receptors improves outcome in both head trauma and focal stroke in rat. J Cardiovasc Pharmacol 2000;36:S357–S361.

    PubMed  CAS  Google Scholar 

  41. Armstead WM. Role of endothelin in pial artery vasoconstriction and altered responses to vasopressin following brain injury. J Neurosurg 1996;85:901–907.

    PubMed  CAS  Google Scholar 

  42. Armstead WM. Hypotension dilates pial arteries by KATP and KCa channel activation. Brain Res. 1999;815:158–164.

    Google Scholar 

  43. Steiner J, Rafols D, Park HK, Katar MS, Rafols JA, Petrov T. Attenuation of iNOS mRNA exacerbates hypoperfusion and upregulates endothelin-1 expression in hippocampus and cortex after brain trauma. Nitric Oxide 2004;10:162–169.

    PubMed  CAS  Google Scholar 

  44. Motte S, McEntee K, Naeije R. Endothelin receptor antagonists. Pharmacol Ther 2006;110(3):386–414.

    PubMed  CAS  Google Scholar 

  45. Ros J, Jones D, Pecinska N, Alessandri B, Boutelle M, Landolt H. Glutamate infusion coupled with hypoxia has a neuroprotective effect in the rat. J Neurosci Methods 2002;119:129–233.

    PubMed  CAS  Google Scholar 

  46. Ros J, Pecinska N, Alessandri B, Landolt H, Fillenz M. Lactate reduces glutamate-induced neurotoxicity in rat cortex. J Neurosci Res 2001;66:790–794.

    PubMed  CAS  Google Scholar 

  47. Choi DW. Ionic dependence of glutamate neurotoxicity. J Neurosci 1987;7(2):369–379.

    PubMed  CAS  Google Scholar 

  48. Morris GF, Bullock R, Marshall SB, Marmarou A, Maas A, Marshall LF. Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two phase III clinical trials. The Selfotel Investigators. J Neurosurg 1999;91(5):737–743.

    CAS  Google Scholar 

  49. Farin A, Marshall LF. Lessons from epidemiologic studies in clinical trials of traumatic brain injury. Acta Neurochir Suppl 2004;89:101–107.

    PubMed  CAS  Google Scholar 

  50. Muir KW. Glutamate-based therapeutic approaches: clinical trials with NMDA antagonists. Curr Opin Pharmacol 2006;6(1):53–60.

    PubMed  CAS  Google Scholar 

  51. Zipfel GJ, Babcock DJ, Lee JM, Choi DW. Neuronal apoptosis after CNS injury: the roles of glutamate and calcium. J Neurotrauma 2000;17(10):857–869.

    PubMed  CAS  Google Scholar 

  52. Hardingham GE, Fukunaga Y, Bading H. Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci 2002;5(5):405–414.

    PubMed  CAS  Google Scholar 

  53. Royo NC, Shimizu S, Schouten JW, Stover JF, McIntosh TK. Pharmacology of traumatic brain injury. Curr Opin 2003;3:27–32.

    CAS  Google Scholar 

  54. Maas AI, Steyerberg EW, Murray GD, Bullock R, Baethmann A, Marshall LF. Why have recent trials of neuroprotective agents in head injury failed to show convincing efficacy? A pragmatic analysis and theoretical considerations. Neurosurgery 1999;44:1286–1298.

    PubMed  Google Scholar 

  55. Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB. Clinical trials in head injury. J Neurotrauma 2002;19:503–557.

    PubMed  Google Scholar 

  56. Bayir H, Kochanek P, Clark RS. Traumatic brain injury in infants and children. Mechanisms of secondary damage and treatment in the intensive care unit. Crit Care Clin 2003;19:529–549.

    Google Scholar 

  57. Doppenberg EM, Choi SC, Bullock R. Clinical trials in traumatic brain injury: lessons for the future. J Neurosurg Anesthesiol 2004;16(1):87–94.

    PubMed  Google Scholar 

  58. Yurkewicz L, Weaver J, Bullock MR, Marshall LF. The effect of the selective NMDA receptor antagonist traxoprodil in the treatment of traumatic brain injury. J Neurotrauma 2005;22:1428–1443.

    PubMed  Google Scholar 

  59. Paschen W. Calcium neurotoxicity. J Neurochem 1999;72(6):2625–2626.

    PubMed  CAS  Google Scholar 

  60. Paschen W, Frandsen A. Endoplasmic reticulum dysfunction–a common denominator for cell injury in acute and degenerative diseases of the brain? J Neurochem 2001;79(4):719–725.

    PubMed  CAS  Google Scholar 

  61. Sattler R, Tymianski M. Molecular mechanisms of calcium-dependent excitotoxicity. J Mol Med 2000;78(1):3–13.

    PubMed  CAS  Google Scholar 

  62. Lee LL, Galo E, Lyeth BG, Muizelaar JP, Berman RF. Neuroprotection in the rat lateral fluid percussion model of traumatic brain injury by SNX-185, an N-type voltage-gated calcium channel blocker. Exp Neurol 2004;190(1):70–78.

    PubMed  CAS  Google Scholar 

  63. Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE. Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death? J Neurosci Res 2005;79:231–239.

    PubMed  CAS  Google Scholar 

  64. Verweij BH, Muizelaar JP, Vinas FC, Peterson PL, Xiong Y, Lee CP. Improvement in mitochondrial dysfunction as a new surrogate efficiency measure for preclinical trials: dose–response and time-window profiles for administration of the calcium channel blocker ziconotide in experimental brain injury. J Neurosurg 2000;93(5):829–834.

    PubMed  CAS  Google Scholar 

  65. Stover JF, Beyer TF, Unterberg AW. Riluzole reduces brain swelling and contusion volume in rats following controlled cortical impact injury. J Neurotrauma 2000;17(12):1171–1178.

    PubMed  CAS  Google Scholar 

  66. Lewen A, Matz P, Chan PH. Free radical pathways in CNS injury. J Neurotrauma 2000;17:871–890.

    PubMed  CAS  Google Scholar 

  67. Pellegrini-Giampietro DE, Cherici G, Alesiani M, Carla V, Moroni F. Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage. J Neurosci 1990;10:1035–1041.

    PubMed  CAS  Google Scholar 

  68. Dykens JA. Isolated cerebral and cerebellar mitochondria produce free radicals when exposed to elevated CA2+ and Na+: implications for neurodegeneration. J Neurochem 1994;63:584–591.

    PubMed  CAS  Google Scholar 

  69. Evans PH. Free radicals in brain metabolism and pathology. Br Med Bull 1993;49:577–587.

    PubMed  CAS  Google Scholar 

  70. Mohanakumar KP, Thomas B, Sharma SM, Muralikrishnan D, Chowdhury R, Chiueh C. Nitric oxide: an antioxidant and neuroprotector. Ann NY Acad Sci 2002;962:389–401.

    PubMed  CAS  Google Scholar 

  71. Lewen A, Fujimura M, Sugawara T, Matz P, Copin JC, Chan PH. Oxidative stress-dependent release of mitochondrial cytochrome c after traumatic brain injury. J Cereb Blood Flow Metab 2001;21:914–920.

    PubMed  CAS  Google Scholar 

  72. Keller JN, Mark RJ, Bruce AJ, Blanc E, Rothstein JD, Uchida K. 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience 1997;80:685–696.

    PubMed  CAS  Google Scholar 

  73. Marklund N, Clausen F, Lewander T, Hillered L. Monitoring of reactive oxygen species production after traumatic brain injury in rats with microdialysis and the 4-hydroxybenzoic acid trapping method. J Neurotrauma 2001;18(11):1217–1227.

    PubMed  CAS  Google Scholar 

  74. Reiter RJ. Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 1995;9:526–533.

    PubMed  CAS  Google Scholar 

  75. Maragos WF, Korde AS. Mitochondrial uncoupling as a potential therapeutic target in acute central nervous system injury. J Neurochem 2004;91:257–262.

    PubMed  CAS  Google Scholar 

  76. Hansson MJ, Persson T, Friberg H, Keep MF, Rees A, Wieloch T, et al. Powerful cyclosporin inhibition of calcium-induced permeability transition in brain mitochondria. Brain Res 2003;960:99–111.

    PubMed  CAS  Google Scholar 

  77. Ichas F, Mazat JP. From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state. Biochem Biophys Acta 1998;1366:33–50.

    PubMed  CAS  Google Scholar 

  78. Lifshitz J, Sullivan PG, Hovda DA, Wieloch T, McIntosh TK. Mitochondrial damage and dysfunction in traumatic brain injury. Mitochondrion 2004;4:705–713.

    PubMed  CAS  Google Scholar 

  79. Sullivan PG, Thompson M, Scheff SW. Continuous infusion of cyclosporin A postinjury significantly ameliorates cortical damage following traumatic brain injury. Exp Neurol 2000;161:631–637.

    PubMed  CAS  Google Scholar 

  80. Scheff SW, Sullivan PG. Cyclosporin A significantly ameliorates cortical damage following experimental traumatic brain injury in rodents. J Neurotrauma 1999;16:783–792.

    PubMed  CAS  Google Scholar 

  81. Arguad L, Gateau-Roesch O, Muntean D, Chalabreysse L, Loufouat J, Robert D, et al. Specific inhibition of the mitochondrial permeability transition prevents lethal reperfusion injury. J Mol Cell Cardiol 2004;38:367–374.

    Google Scholar 

  82. Singleton RH, Stone JR, Okonkwo DO, Pellicane AJ, Povlishock JT. The immunophilin ligand FK506 attenuates axonal injury in an impact-acceleration model of traumatic brain injury. J Neurotrauma 2001;18:607–614.

    PubMed  CAS  Google Scholar 

  83. Suehiro E, Singleton RH, Stone JR, Povlishock JT. The immunophilin ligand FK506 attenuates the axonal damage associated with rapid rewarming following posttraumatic hypothermia. Exp Neurol 2001;172:199–210.

    PubMed  CAS  Google Scholar 

  84. Price M, Lang MG, Frank AT, Goetting-Minesky MP, Patel SP, Silviera ML, et al. Seven cDNAs enriched following hippocampal lesion: possible roles in neuronal responses to injury. Brain Res Mol Brain Res 2003;117:58–67.

    PubMed  CAS  Google Scholar 

  85. Kurz JE, Hamm RJ, Singleton RH, Povlishock JT, Churt SB. A persistent change in subcellular distribution of calcineurin following fluid percussion injury in the rat. Brain Res 2005;1048:153–160.

    PubMed  CAS  Google Scholar 

  86. Kurz JE, Parsons JT, Rana A, Gibson CJ, Hamm RJ, Churn SB. A significant increase in both basal and maximal calcineurin activity following fluid percussion injury in the rat. J Neurotrauma 2005;22:476–490.

    PubMed  Google Scholar 

  87. Sullivan PG. Mitochondrial uncoupling as a therapeutic target following neuronal injury. J Bioenergeics Biomembranes 2004;36:353–356.

    CAS  Google Scholar 

  88. Korde AS, Pettigrew LC, Craddock SD, Maragos WF. The mitochondrial uncoupler 2,4-dinitrophenol attenuates tissue damage and improves mitochondrial homeostasis following transient focal cerebral ischemia. J Neurochem 2005;94(6):1676–1684.

    PubMed  CAS  Google Scholar 

  89. Mattiasson G, Shamloo M, Gido G, Mathi K, Tomasevic G, Yi S, et al. Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat Med 2003;9:1062–1068.

    PubMed  CAS  Google Scholar 

  90. Roshon MJ, Kline JA, Thornton LR, Watts JA. Cardiac UCP2 expression and myocardial oxidative metabolism during acute septic shock in the rat. Shock 2003;19(6):570–576.

    PubMed  CAS  Google Scholar 

  91. Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, et al. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab 2005;25:763–774.

    PubMed  CAS  Google Scholar 

  92. Wong J, Hoe MW, Zhiwei F, Ng I. Apoptosis and Traumatic Brain Injury. Neurocrit Care 2005;3:177–182.

    PubMed  CAS  Google Scholar 

  93. Zhang X, Chen Y, Jenkins LW, Kochanek P, Clark RS. Bench-to-bedside review: apoptosis/programmed cell death triggered by traumatic brain injury. Critical Care 2005;9:66–75.

    PubMed  CAS  Google Scholar 

  94. Clark RS, Kochanek P, Watkins SC. Caspase-3 mediated neuronal death after traumatic brain injury in rats. J Neurochem 2000;74:740–753.

    PubMed  CAS  Google Scholar 

  95. Yakovlev AG, Ota K, Wang G, Movsesyan V, Bao WL, Yoshihara K, et al. Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury. J Neurosci 2001;21(19):7439–7446.

    PubMed  CAS  Google Scholar 

  96. Besson VC, Zsengeller Z, Plotkine M, Szabo C, Marchand-Verrecchia C. Beneficial effects of PJ34 and INO-1001, two novel water-soluble poly(ADP-ribose) polymerase inhibitors, on the consequences of traumatic brain injury in rat. Brain Res 2005;1041:149–156.

    PubMed  CAS  Google Scholar 

  97. Hong SJ, Dawson TM, Dawson VL. Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling. Trends Pharmacol Sci 2004;25:259–264.

    PubMed  CAS  Google Scholar 

  98. Koh DW, Dawson TM, Dawson VL. Mediation of cell death by poly (ADP-ribose) polymerase-1. Pharmacol Res 2005;52:5–14.

    PubMed  CAS  Google Scholar 

  99. Li LY, Luo X, Wang X. Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 2001;412:95–99.

    PubMed  CAS  Google Scholar 

  100. Graham SH, Chen J, Clark RS. BcI-2 family gene products in cerebral ischemia and traumatic brain injury. J Neurotrauma 2000;17:831–841.

    PubMed  CAS  Google Scholar 

  101. Concha NO, Abdel-Meguid SS. Controlling apoptosis by inhibition of caspases. Curr Medicinal Chem 2002;9:713–726.

    CAS  Google Scholar 

  102. Clark RS, Kochanek PM, Schwartz MA, Schiding JK, Turner DS, Chen M, et al. Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats. Pediatr Res 1996;39:784–790.

    PubMed  CAS  Google Scholar 

  103. Ang BT, Yap E, Lim J, Tan WL, Ng PY, Ng I, et al. Poly(adenosine diphosphate-ribose) polymerase expression in human traumatic brain injury. J Neurosurg 2003;99(1):125–130.

    PubMed  CAS  Google Scholar 

  104. Lenzlinger PM, Marx A, Trentz O, Kossman T, Morganti-Kossman MC. Prolonged intrathecal release of soluble Fas following severe traumatic brain injury in humans. J Neuroimmunol 2002;122:167–174.

    PubMed  CAS  Google Scholar 

  105. Ng I, Yeo TT, Tang WY, Soong R, Ng PY, Smith DR. Apoptosis occurs after cerebral contusions in humans. Neurosurgery 2000;46(4):949–956.

    PubMed  CAS  Google Scholar 

  106. Williams S, Raghupathi R, MacKinnon MA, McIntosh TK, Saatman KE, Graham DI. In situ DNA fragmentation occurs in white matter up to 12 months after head injury in man. Acta Neuropathol (Berl) 2001;102(6):581–590.

    CAS  Google Scholar 

  107. Biegon A. Cannabinoids as neuroprotective agents in traumatic brain injury. Curr Pharm Design 2004;10:2177–2183.

    CAS  Google Scholar 

  108. Mechoulam R, Spatz M, Shohami E. Endocannabinoids and neuroprotection. Science 2002;129:1–6.

    Google Scholar 

  109. Panikashvill D, Simeonidou C, Ben-Shabat S, Hanus L, Breuer A, Mechoulam R, et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001;413:527–531.

    Google Scholar 

  110. Knoller N, Levi L, Shoshan I, Reichenthal E, Razon N, Rappaport ZH, et al. Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial. Crit Care Med 2002;30:548–554.

    PubMed  CAS  Google Scholar 

  111. Shohami E, Mechoulam R. Dexanabinol (HU-211): A nonpsychotropic cannabinoid with neuroprotective properties. Drug Dev Res 2000;50:211–215.

    CAS  Google Scholar 

  112. Ungerstedt U, Rostami E. Microdialysis in neurointensive care. Curr Pharm Design 2004;10:2145–2152.

    CAS  Google Scholar 

  113. Grate LL, Golden JA, Hoopes PJ, Hunter JV, Duhaime AC. Traumatic brain injury in piglets of different ages: techniques for lesion analysis using histology and magnetic resonance imaging. J Neurosci Methods 2003;123:201–206.

    PubMed  Google Scholar 

  114. Armstead WM. Age dependent NMDA contribution to impaired hypotensive cerebral hemodynamics following brain injury. Dev Brain Res 2002;139:19–28.

    CAS  Google Scholar 

  115. Smith SL, Andous PK, Gleason DG, Hall ED. Infant rat model of the shaken baby syndrome: preliminary characterization and evidence for the role of free radicals in cortical hemorrhaging and progressive neuronal degeneration. J Neurotrauma 1998;15:693–705.

    PubMed  CAS  Google Scholar 

  116. Robertson CL. Mitochondrial dysfunction contributes to cell death following traumatic brain injury in adult and immature animals. J Bioenergeics Biomembranes 2004;36:363–368.

    CAS  Google Scholar 

  117. Armstead WM, Kurth CD. Different cerebral hemodynamic responses following fluid percussion brain injury in the newborn and juvenile pig. J Neurotrauma 1994;11:487–497.

    PubMed  CAS  Google Scholar 

  118. Bittigau P, Sifringer M, Pohl D. Apoptotic neurodegeneration following trauma is markedly enhanced in the immature brain. Ann Neurol 1999;45:724–735.

    PubMed  CAS  Google Scholar 

  119. Prins ML, Hovda DA. Fluid percussion brain injury in the developing rat: effects of the maturation on Morris water maze acquisition. J Neurotrauma 1998;15:799–811.

    PubMed  CAS  Google Scholar 

  120. Dumitriu IE, Baruah P, Manfredi AA, Bianchi ME, Rovere-Querini P. HMGB1: guiding immunity from within. Trends Immunol 2005;26(7):381–387.

    PubMed  CAS  Google Scholar 

  121. Doughty L. Modulation of the immune response in critical illness/injury. In: Doughty LA, Linden P, eds. Immunology and Infectious Disease. Norwell, MA: Kluwer Academic Publishers; 2003:115–154.

    Google Scholar 

  122. Riedemann NC, Guo RF, Ward PA. Novel strategies for the treatment of sepsis. Nat Med 2003;9:517–524.

    PubMed  CAS  Google Scholar 

  123. Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003;101:3765–3777.

    PubMed  CAS  Google Scholar 

  124. Aird WC. Coagulation. Crit Care Med 2005;33:S485.

    PubMed  Google Scholar 

  125. Esmon CT. The interactions between inflammation and coagulation. Br J Haematol 2005;131:417–430.

    PubMed  CAS  Google Scholar 

  126. Opal SM, Esmon CT. Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis. Crit Care 2003;7:23–38.

    PubMed  Google Scholar 

  127. Han KH, Hong KH, Park JH, Ko J, Kang DH, Choi KJ, et al. C-reactive protein promotes monocyte chemoattractant protein-1–mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes. Circulation 2004;109:2566–2571.

    PubMed  CAS  Google Scholar 

  128. Han KH, Tangirala RK, Green SR. Chemokine receptor CCR2 expression and monocyte chemoattractant protein-1 mediated chemotaxis in human monocytes: a regulatory role for plasma low-density lipoprotein. Arterioscler Thromb Vasc Biol 1998;17:1983–1991.

    Google Scholar 

  129. Wolbink GJ, Bossink AW, Groeneveld AB, DeGroot MC, Thijs LG, Hack CE. Complement activation in patients with sepsis is in part mediated by C-reactive protein. J Infect Dis 1998;177:81–87.

    PubMed  CAS  Google Scholar 

  130. Singh U, Devaraj S, Jialal I. C-reactive protein decreases tissue plasminogen activator activity in human aortic endothelial cells: evidence that C-reactive protein is a procoagulant. Arterioscler Thromb Vasc Biol 2005;25:2216–2221.

    PubMed  CAS  Google Scholar 

  131. Nan B, Yang H, Yan S, Lin PH, Lumsden AB, Yao Q, et al. C-reactive protein decreases expression of thrombomodulin and endothelial protein C receptor in human endothelial cells. Surgery 2005;138:212–222.

    PubMed  Google Scholar 

  132. Bernardo A, Ball C, Nolasco L, Moake JF, Dpmg J. Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow. Blood 2004;104:100–106.

    PubMed  CAS  Google Scholar 

  133. Opal SM. Therapeutic rationale for antithrombin III in sepsis. Crit Care Med 2000;28:S34–S37.

    PubMed  CAS  Google Scholar 

  134. Voss R, Matthias FR, Borkowski G, Reitz D. Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit. Br J Haematol 1990;75(1):99–105.

    PubMed  CAS  Google Scholar 

  135. Zeerleder S, Schroeder V, Hack CE, Kohler HP, Wuillemin WA. TAFI and PAI-1 levels in human sepsis. Thromb Res 2006;118(2):205–212.

    PubMed  CAS  Google Scholar 

  136. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001;286(15):1869–1878.

    PubMed  CAS  Google Scholar 

  137. Conway EM. The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kB and mitogen-activated protein kinase pathways. J Exp Med 2002;196:565–577.

    PubMed  CAS  Google Scholar 

  138. Abeyama K, Stern DM, Ito Y, Kawahara KI, Yoshimoto Y, Tanaka M, et al. The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism. J Clinical Invest 2005;115:1267–1274.

    CAS  Google Scholar 

  139. Kearon C, Comp C, Douketis D, Royds R, Yamada K, Gent M. A dose–response study of a recombinant human soluble thrombomodulin (ART-123) for prevention of venous thromboembolism after unilateral total hip replacement. J Thromb Haemost 2003;Abstract 0C330.

    Google Scholar 

  140. Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989;264:4743–4746.

    PubMed  CAS  Google Scholar 

  141. Esmon CT. The protein C pathway. Chest 2003;124:26–32.

    Google Scholar 

  142. Macias WL, Yan SB, Williams MD, Um SL, Sandusky GE, Ballard DW, et al. New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated). Crit Care 2005;9:S38–S45.

    PubMed  Google Scholar 

  143. Faust SN, Levin M, Harrison OB, Goldin RD, Lockhart MS. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med 2001;345:408–416.

    PubMed  CAS  Google Scholar 

  144. Conway EM, Rosenberg RD. Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. Mol Cell Biol 1988;8:5588–5592.

    PubMed  CAS  Google Scholar 

  145. Takano S, Kimura S, Ohdama S, Aoki N. Plasma thrombomodulin in health and diseases. Blood 1990;76:2024–2029.

    PubMed  CAS  Google Scholar 

  146. Glaser CB, Morser J, Clarke JH, Blasko E, McLean K, Kuhn I, et al. Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity. A potential rapid mechanism for modulation of coagulation. J Clin Invest 1992;90(6):2565–2573.

    PubMed  CAS  Google Scholar 

  147. Bernard GR, Ely EW, Wright TJ, Fraiz J, Stasek JE, Russell JA, et al. Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis. Crit Care Med 2001;29:2051–2059.

    PubMed  CAS  Google Scholar 

  148. Macias WL, Khainaut JF, Yan SC, Helterbrand JD, Seger M, Johnson G, et al. Pharmacokinetic–pharmacodynamic analysis of drotrecogin alfa (activated) in patients with severe sepsis. Clin Pharmacol Ther 2002;72:391–402.

    PubMed  CAS  Google Scholar 

  149. Joyce DE, Gelbert L, Ciaccia A, DeHoff B, Grinnell BW. Gene expression profile of antithrombotic protein C defines new mechanisms modulating inflammation and apoptosis. J Biol Chem 2001;276:11199–11203.

    PubMed  CAS  Google Scholar 

  150. Sturn DH, Kaneider NC, Feistritzer C, Djanani A, Fukudome K, Wiedermann CJ. Expression and function of the endothelial protein C receptor in human neutrophils. Blood 2003;102:1499–1505.

    PubMed  CAS  Google Scholar 

  151. Feistritzer C, Lenta R, Riewald M. Protease-activated receptors-1 and -2 can mediate endothelial barrier protection: role in factor Xa signaling. J Thromb Haemost 2005;3:2798–2805.

    PubMed  CAS  Google Scholar 

  152. Riewald M, Ruf W. Science review: role of coagulation protease cascades in sepsis. Crit Care 2003;7:123–129.

    PubMed  Google Scholar 

  153. Bannerman DD, Tupper JC, Ricketts WA, Bennett CF, Winn RK, Harlan JM. A constitutive cytoprotective pathway protects endothelial cells from lipopolysaccharide-induced apoptosis. J Biol Chem 2001;276(18):14924–1432.

    PubMed  CAS  Google Scholar 

  154. Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriquez AL, et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003;290:238–247.

    PubMed  CAS  Google Scholar 

  155. Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005;353:1332–1341.

    PubMed  CAS  Google Scholar 

  156. Deans KJ, Haley M, Natanson C, Eichacker PQ, Minneci PC. Novel therapies for sepsis: a review. J Trauma 2005;58:867–874.

    PubMed  Google Scholar 

  157. Eichacker PQ, Parent C, Kalil A, Esposito C, Cui X, Banks SM, et al. Risk and the efficacy of antiinflammatory agents. Am J Respir Crit Care Med 2002;166:1197–1205.

    PubMed  Google Scholar 

  158. Wang H. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 2004;10:1216–1221.

    PubMed  CAS  Google Scholar 

  159. Yang H, Wang H, Czura CJ, Tracey KJ. The cytokine activity of HMGB1. J Leukocyte Biol 2005;78:1–8.

    PubMed  CAS  Google Scholar 

  160. Park JS, Gamboni-Robertson F, He Q, Svetkauskaite D, Kim JY, Strassheim D, et al. High mobility group box 1 protein (HMGB1) interacts with multiple toll like receptors. Am J Physiol Cell Physiol 2006:290(3):C917–C924.

    PubMed  CAS  Google Scholar 

  161. Andersson U, Erlandsson-Harris H, Yang H, Tracey KJ. HMGB1 as a DNA-binding cytokine. J Leukocyte Biol 2002;72:1084–1091.

    PubMed  CAS  Google Scholar 

  162. Fluza C. Inflammatory promoting activity of HMGB1 on human microvascular endothelial cells. Blood 2002;101:2652–2660.

    Google Scholar 

  163. Sappington PL. HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice. Gastroenterology 2002;123:790–802.

    PubMed  CAS  Google Scholar 

  164. Sunden-Cullberg J, Norrby-Teglund A, Rouhiainen A, Rauvala H, Herman G, Tracey KJ, et al. Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock. Crit Care Med 2005;34:564–573.

    Google Scholar 

  165. Li J. Structural basis for the proinflammatory cytokine activity of high mobility group box 1. Mol Med 2003;9:37–45.

    PubMed  CAS  Google Scholar 

  166. Ulloa L. Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc Natl Acad Sci USA 2002;99:12351–12356.

    PubMed  CAS  Google Scholar 

  167. Roger T, David J, Glauser MP, Calandra T. MF regulates innate immune responses through modulation of Toll-like receptor 4. Nature 2001;414:920–923.

    PubMed  CAS  Google Scholar 

  168. Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, et al. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 1993;365(6448):756–759.

    PubMed  CAS  Google Scholar 

  169. Calandra T, Bernhagen J, Metz CN, Spiegel LA, Macher M, Donnelly T, et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature 1995;365:756–759.

    Google Scholar 

  170. Leng L, Bucala R. Macrophage migration inhibitory factor. Crit Care Med 2005;33(12 Suppl):S475–S477.

    PubMed  Google Scholar 

  171. Mitchell RA, Liao H, Chesney J, Fingerle-Rowson G, Baugh J, David J, et al. Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innage immune response. Proc Natl Acad Sci USA 2002;99:345–350.

    PubMed  CAS  Google Scholar 

  172. Maxime V, Fitting C, Annane D, Cavaillon JM. Corticoids normalize leukocyte production of macrophage migration inhibitory factor in septic shock. J Infect Dis 2005;191:138–144.

    PubMed  CAS  Google Scholar 

  173. Carcillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA 1991;266:1242–1245.

    PubMed  CAS  Google Scholar 

  174. Han YY, Carcillo JA, Dragotta MA, Bills DM, Watson RS, Westerman ME, et al. Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics 2003;112:793–799.

    PubMed  Google Scholar 

  175. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Eng J Med 2001;345:1368–1377.

    CAS  Google Scholar 

  176. Spronk PE, Zandstra DF, Ince C. Bench-to-bedside review: sepsis is a disease of the microcirculation. Crit Care 2004;8:462–468.

    PubMed  Google Scholar 

  177. Sibbald WJ. Shockingly complex: the difficult road to introducing new ideas to critical care. Crit Care 2004;8:419–421.

    PubMed  Google Scholar 

  178. Hayes MA, Timmins AC, Yau EHS, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically patients. N Engl J Med 1994;330:1717–1722.

    PubMed  CAS  Google Scholar 

  179. Gattinoni L, Brazzi L, Pelosi P, Latini R, Tagnoni G, Pesenti A, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med. 1995;333:1025–1032.

    PubMed  CAS  Google Scholar 

  180. Crouser ED. Mitochondrial dysfunction in septic shock and multiple organ dysfunction syndrome. Mitochondrion 2004;4:729–741.

    PubMed  CAS  Google Scholar 

  181. Hayes MA, Timmins AC, Yau EH, Palazzo M, Watson D, Hinds CJ. Oxygen transport patterns in patients with sepsis syndrome or septic shock: influence of treatment and relationship to outcome. Crit Care Med 1997;25:926–936.

    PubMed  CAS  Google Scholar 

  182. Fink MP. Bench-to-bedside review: cytopathic hypoxia. Crit Care 2002;6:491–499.

    PubMed  Google Scholar 

  183. Hotchkiss RS, Song SK, Neil JJ, Chen RD, Manchester JK, Karl IE, et al. Sepsis does not impair tricarboxylic acid cycle in the heart. Am J Physiol 1991;260(1 Pt 1):C50–C57.

    PubMed  CAS  Google Scholar 

  184. Astiz M, Rackow EC, Weil MH, Schumer W. Early impairment of oxidative metabolism and energy production in severe sepsis. Circ Shock 1988;26(3):311–320.

    PubMed  CAS  Google Scholar 

  185. Rosser DM, Stidwill RP, Jacobson D, Singer M. Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis. J Appl Physiol 1995;79(6):1878–1882.

    PubMed  CAS  Google Scholar 

  186. Boekstegers P, Weidenhofer S, Pilz G, Werdan K. Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock. Infection 1991;19(5):317–323.

    PubMed  CAS  Google Scholar 

  187. Sair M, Etherington PJ, Peter Winlove C, Evans TW. Tissue oxygenation and perfusion in patients with systemic sepsis. Crit Care Med 2001;29(7):1343–1349.

    PubMed  CAS  Google Scholar 

  188. Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 2002;360:219–223.

    PubMed  CAS  Google Scholar 

  189. Fink MP. Cytopathic hypoxia: mitochondrial dysfunction as mechanism contribution to organ dysfunction in sepsis. Crit Care Clin 2001;17:219–237.

    PubMed  CAS  Google Scholar 

  190. Cuzzocrea S. Shock, inflammation and PARP. Pharmacol Res 2005;52:72–82.

    PubMed  CAS  Google Scholar 

  191. Vary TC, Siegel JH, Nakatani T, Sato T, Aoyama H. Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol 1986;250:E634–E640.

    PubMed  CAS  Google Scholar 

  192. von Haefen C, Wieder T, Gillissen B, Starck L, Graupner V, Dorken B, et al. Ceramide induces mitochondrial activation and apoptosis via a Bax-dependent pathway in human carcinoma cells. Oncogene 2002;21(25):4009–4019.

    Google Scholar 

  193. Kim BC, Kim HT, Mamura M, Ambudkar IS, Choi KS, Kim SJ. Tumor necrosis factor induces apoptosis in hepatoma cells by increasing C12+release from the endoplasmic reticulum and suppressing Bc1–2 expression. J Biol Chem 2002;277:31381–31389.

    PubMed  CAS  Google Scholar 

  194. Tsujimoto Y. Bcl-2 family of proteins: life-or-death switch in mitochondria. Biosci Rep 2002;22(1):47–58.

    PubMed  CAS  Google Scholar 

  195. Coopersmith CM, Stromberg PE, Dunne WM, Davis CG, Amiot DM, Buchman TG, et al. Inhibition of intestinal epithelial apoptosis and survival in a murine model of pneumonia-induced sepsis. JAMA 2002;287:1716–1721.

    PubMed  Google Scholar 

  196. Coopersmith CM, Chang KC, Swanson PE, Tinsley KW, Stromberg PE, Buchman TG, et al. Overexpression of Bc1–2 in the intestinal epithelium improves survival in septic mice. Crit Care Med 2002;30:195–201.

    PubMed  CAS  Google Scholar 

  197. Tavakoli H, Mela L. Alterations of mitochondrial metabolism and protein concentrations in subacute septicemia. Infect Immun 1982;38(2):536–541.

    PubMed  CAS  Google Scholar 

  198. Prins JB, Ledgerwood EC, Ameloot P, Vandenabeele P, Faraco PR, Bright NA, et al. Tumor necrosis factor–induced cytotoxicity is not related to rates of mitochondrial morphological abnormalities or autophagy-changes that can be mediated TNFR-I or TNFR-II. Biosci Rep 1998;18:329–340.

    PubMed  CAS  Google Scholar 

  199. Jezek P, Hlavata L. Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. International J Biochem Cell Biol 2005;37:2478–2503.

    CAS  Google Scholar 

  200. Kizaki T, Suzuki K, Hitomi Y, Taniguchi N, Saitoh D, Watanabe K, et al. Uncoupling protein 2 plays an important role in nitric oxide production of lipopolysaccharide-stimulated macrophages. Proc Natl Acad Sci USA 2002;99(14):9392–9397.

    PubMed  CAS  Google Scholar 

  201. Ryu JW, Hong KH, Maeng JH, Kim JB, Ko J, Park JY, et al. Overexpression of uncoupling protein 2 in THP1 monocytes inhibits b2, integrin-mediated firm adhesion and transendothelial migration. Arterioscler Thromb Vasc Biol 2004;24:864–870.

    PubMed  CAS  Google Scholar 

  202. Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol 2005;6:1191–1197.

    PubMed  CAS  Google Scholar 

  203. Serhan CN. Novel w—3–derived local mediators in anti-inflammation and resolution. Pharmacol Ther 2005;105:7–21.

    PubMed  CAS  Google Scholar 

  204. Nathan C. Points of control in inflammation. Nature 2002;420:846–852.

    PubMed  CAS  Google Scholar 

  205. Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2001;2:612–619.

    PubMed  CAS  Google Scholar 

  206. Godson C. Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol 2000;164:1663–1667.

    PubMed  CAS  Google Scholar 

  207. Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, et al. Molecular circuits of resolution: formation and actions of resolvins and protectins1. J Immunol 2005;174:4345–4355.

    PubMed  CAS  Google Scholar 

  208. Calder PC. n-3 fatty acids, inflammation, and immunity—relevance to postsurgical and critically ill patients. Lipids 2004;39(12):1147–1161.

    PubMed  CAS  Google Scholar 

  209. Mekontso-Dessap A, Brun-Buisson C. Statins: the next step in adjuvant therapy for sepsis? Intensive Care Med 2006;32:11–14.

    PubMed  Google Scholar 

  210. Schonbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors. Statins as antiinflammatory agents? Circulation 2004;109:II-18–II-26.

    Google Scholar 

  211. Krysiak R, Okopien B, Herman Z. Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes. Drugs 2003;63:1821–1854.

    PubMed  CAS  Google Scholar 

  212. Merx MW, Liehn EA, Graf J, van de Sandt A, Schaltenbrand M, Schrader J, et al. Statin treatment after onset of sepsis in a murine model improves survival. Circulation 2005;112(1):117–124.

    PubMed  CAS  Google Scholar 

  213. Steiner S, Speidl WS, Pleiner J, Seidinger D, Zorn G, Kaun C, et al. Simvastatin blunts endotoxin-induced tissue factor in vivo. Circulation 2005;111:1841–1846.

    PubMed  CAS  Google Scholar 

  214. Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, et al. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 2004;110:880–885.

    PubMed  CAS  Google Scholar 

  215. Kruger P, Fitzsimmons K, Cook D, Jones M, Nimmo G. Statin therapy is associated with fewer deaths in patients with bacteraemia. Intensive Care Med 2006;32:75–79.

    PubMed  Google Scholar 

  216. Liappis AP, Kan VL, Rochester CG, Simon GL. The effect of statins on mortality in patients with bacteremia. Clin Infect Dis 2001;33:1352–1357.

    PubMed  CAS  Google Scholar 

  217. Arcaroli J, Fessler MB, Abraham E. Genetic polymorphisms and sepsis. Shock 2005;24:300–312.

    PubMed  CAS  Google Scholar 

  218. Schroder NWJ, Schumann RR. Single nucleotide polymorphisms of toll-like receptors and susceptibility to infections disease. Lancet Infect Dis 2005;5:156–164.

    PubMed  Google Scholar 

  219. Wheeler DS, Wong HR. The impact of molecular biology on the practice of pediatric critical care medicine. Pediatr Crit Care Med 2001;2:299–310.

    PubMed  CAS  Google Scholar 

  220. Feezor RJ, Cheng A, Paddock HN, Baker HV, Moldawer LL. Functional genomics and gene expression profiling in sepsis: beyond class prediction. Clin Infect Dis 2005;41:S427–S435.

    PubMed  CAS  Google Scholar 

  221. Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, et al. A network-based analysis of systemic inflammation in humans. Nature 2005;437:1032–1037.

    PubMed  CAS  Google Scholar 

  222. Hoehn GT, Suffredini AF. Proteomics. Crit Care Med 2005;33(12 Suppl):S444–S448.

    PubMed  Google Scholar 

  223. Zemans RL, Matthay MA. Bench-to-bedside review: the role of the alveolar epithelium in the resolution of pulmonary edema in acute lung injury. Critical Care 2004;8:469–477.

    PubMed  Google Scholar 

  224. Matthay MA, Zimmerman GA. Acute lung injury and the acute respiratory distress syndrome. Am J Respir Cell Mol Biol 2005; 33:319–327.

    PubMed  CAS  Google Scholar 

  225. Minakata Y, Suzuki S, Grygorczyk C, Dagenais A, Berthiaume Y. Impact of β-adrenergic agonists on Na channel and Na/K ATPase expression in alveolar type II cells. Am J Physiol 1998;275:L414–L422.

    PubMed  CAS  Google Scholar 

  226. Saldias FJ, Comellas A, Ridge KM, Lecuona E, Sznajder JI. Isoproterenol improves ability of lung to clear edema in rats exposed to hyperoxia. J Appl Physiol 1999;87:30–35.

    PubMed  CAS  Google Scholar 

  227. Borjesson A, Norlin A, Wang X, Anderson R, Folkesson HG. TNF-alpha stimulates alveolar liquid clearance during intestinal ischemia-reperfusion in rats. Am J Physiol Lung Cell Mol Physiol 2000;278:L3–L12.

    PubMed  CAS  Google Scholar 

  228. Matthay MA, Folkesson HG, Clerici C. Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Res 2002;82:569–600.

    CAS  Google Scholar 

  229. Perkins GD, McAuley DF, Thickett DR, Gao F. The β-agonists lung injury trial (BALTI). A randomized placebo-controlled clinical trial. Am J Respir Crit Care Med 2006;173:281–287.

    CAS  Google Scholar 

  230. Perkins GD, McAuley DF, Richter A, Thickett DR, Gao F. Bench-to-bedside review: β2-Agonists and the acute respiratory distress syndrome. Crit Care 2004;8:25–32.

    PubMed  Google Scholar 

  231. Mutlu GM, Dumasius V, Burhop J, McShane PJ, Meng FJ, Welch L, et al. Upregulation of alveolar epithelial active Na+ transport is dependent on β2-adrenergic receptor signaling. Circ Res 2004;94:1091–1100.

    PubMed  CAS  Google Scholar 

  232. Sartori C, Allemann Y, Duplain H, Lepori M, Egli M, Lipp E, et al. Salmeterol for the prevention of high-altitude pulmonary edema. N Engl J Med 2002;346:1631–1636.

    PubMed  CAS  Google Scholar 

  233. Gobran LI, Rooney SA. Regulation of SP-B and SP-C secretion in rat type II cells in primary culture. Am J Physiol Lung Cell Mol Physiol 2001;281(6):L1413–L1419.

    PubMed  CAS  Google Scholar 

  234. Schultz MJ, Haitsma JJ, Zhang H, Slutsky AS. Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia—a review. Crit Care Med 2006;34:1–7.

    Google Scholar 

  235. Idell S. Coagulation, fibrinolysis, and fibrin deposition in acute lung injury. Crit Care Med 2003;31:S213–S220.

    PubMed  CAS  Google Scholar 

  236. Miller DL, Welty-Wolf K, Carraway MS. Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide. Am J Respir Cell Mol Biol 2002;26:650–658.

    PubMed  CAS  Google Scholar 

  237. Ware LB, Bastarache JA, Wang L. Coagulation and fibrinolysis in human acute lung injury—new therapeutic targets? Keio J Med 2005;54:142–149.

    PubMed  CAS  Google Scholar 

  238. Laterre PF, Wittebole X, Dhainaut JF. Anticoagulant therapy in acute lung injury. Crit Care Med 2003;31:S329–S336.

    PubMed  CAS  Google Scholar 

  239. Yasui H, Gabazza EC, Tamaki S. Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse. Am J Respir Crit Care Med 2001;163:1660–1668.

    PubMed  CAS  Google Scholar 

  240. VanderPoll T, Levi M, Nick JA, Abraham E. Activated protein C inhibits local coagulation after intrapulmonary delivery of endotoxin in humans. Am J Respir Crit Care Med 2005;171:1125–1128.

    Google Scholar 

  241. Idell S, Koenig KB, Fair DS. Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome. Am J Physiol 1991;261:L240–L248.

    PubMed  CAS  Google Scholar 

  242. Gunther M, Mosavi P, Heinemann S. Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. Am J Respir Crit Care Med 2000;161:454–462.

    PubMed  CAS  Google Scholar 

  243. Prabhakaran P, Ware LB, White KE. Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury. Am J Physiol Lung Cell Mol Physiol 2003;285:L20–L28.

    PubMed  CAS  Google Scholar 

  244. Schultz MJ, Millo J, Levi M. Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia. Thorax 2004;59:130–135.

    PubMed  CAS  Google Scholar 

  245. Jin Y, Choi AM. Cytoprotection of heme oxygenase-1/carbon monoxide in lung injury. Proc Am Thorac Soc 2005;2:232–235.

    PubMed  CAS  Google Scholar 

  246. Morse D, Choi AM. Heme oxygenase-1. From bench-to-bedside. Am J Respir Crit Care Med 2005;172:660–670.

    PubMed  Google Scholar 

  247. Kim HP, Wang X, Zhang J, Suh GY, Benjamin IJ, Ryter SW, et al. Heat shock protein-70 mediates the cytoprotective effect of carbon monoxide: involvement of P38b MAPK and heat shock factor-11. J Immunol 2005;175:2622–2629.

    PubMed  CAS  Google Scholar 

  248. Mazzola S, Forni M, Albertini M, Bacci ML, Zannoni A, Gentilini F, et al. Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs. FASEB J 2005;19(4):2045–2047.

    PubMed  CAS  Google Scholar 

  249. Fredenburgh LE, Baron RM, Carvajal IM, Mouded M, Macias AA, Ith B, et al. Absence of oxygenase-1 expression in the lung parenchyma exacerbates endotoxin-induced acute lung injury and decreases surfactant protein-B levels. Cell Mol Biol 2005;51:513–520.

    PubMed  CAS  Google Scholar 

  250. Dennery PA, Spitz DR, Yang G, Tatarov A, Lee CS, Shegog ML, et al. Oxygen toxicity and iron accumulation in the lungs of mice lacking heme oxygenase-2. J Clin Invest 1998;101:1001–1011.

    PubMed  CAS  Google Scholar 

  251. Dennery PA, Visner G, Weng YH, Nguyen X, Lu F, Zander D, et al. Resistance to hyperoxia with heme oxygenase-1 disruption: role of iron. Free Radic Biol Med 2003;34:124–133.

    PubMed  CAS  Google Scholar 

  252. Gopinathan V, Miller NJ, Milner AD, Rice-Evans CA. Bilirubin and ascorbate antioxidant activity in neonatal plasma. FEBS Lett 1994;349:197–200.

    PubMed  CAS  Google Scholar 

  253. Meyer J, Prien T, Aken HV, Bone HG, Waurick R, Theilmeier G, et al. Arterio-venous carboxyhemoglobin difference suggests carbon monoxide production by human lungs. Biochem Biophys Res Commun 1998;244:230–232.

    PubMed  CAS  Google Scholar 

  254. Motterlini R, Clark JE, Foresti R, Sarathchandra P, Mann BE, Green CJ. Carbon monoxide-releasing molecules. Characterization of biochemical and vascular activities. Circ Res 2002;90:e17–e24.

    PubMed  CAS  Google Scholar 

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© 2009 Springer-Verlag London

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Doughty, L.A. (2009). Molecular Biology in the Pediatric Intensive Care Unit. In: Wheeler, D., Wong, H., Shanley, T. (eds) Science and Practice of Pediatric Critical Care Medicine. Springer, London. https://doi.org/10.1007/978-1-84800-921-9_15

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  • DOI: https://doi.org/10.1007/978-1-84800-921-9_15

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