M P Fink

Summary

Affiliation: University of Pittsburgh
Country: USA

Publications

  1. pmc Bench-to-bedside review: Amelioration of acute renal impairment using ethyl pyruvate
    Michael C Reade
    Austin Hospital University of Melbourne, Heidelberg, Melbourne, Victoria, Australia
    Crit Care 9:556-60. 2005
  2. pmc Equipment review: the success of early goal-directed therapy for septic shock prompts evaluation of current approaches for monitoring the adequacy of resuscitation
    Scott R Gunn
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Crit Care 9:349-59. 2005
  3. ncbi request reprint Hemigramicidin-TEMPO conjugates: novel mitochondria-targeted anti-oxidants
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States
    Biochem Pharmacol 74:801-9. 2007
  4. ncbi request reprint Ethyl pyruvate: a novel anti-inflammatory agent
    M P Fink
    Departments of Critical Care Medicine, Pharmacology and Surgery, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA
    J Intern Med 261:349-62. 2007
  5. ncbi request reprint Intestinal epithelial hyperpermeability: update on the pathogenesis of gut mucosal barrier dysfunction in critical illness
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15260, USA
    Curr Opin Crit Care 9:143-51. 2003
  6. ncbi request reprint Hemigramicidin-TEMPO conjugates: novel mitochondria-targeted antioxidants
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Crit Care Med 35:S461-7. 2007
  7. pmc Pathophysiology of intensive care unit-acquired anemia
    Mitchell P Fink
    Anesthesiology and Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA
    Crit Care 8:S9-10. 2004
  8. ncbi request reprint Research: advances in cell biology relevant to critical illness
    Mitchell P Fink
    Departments of Critical Care Medicine and Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Curr Opin Crit Care 10:279-91. 2004
  9. ncbi request reprint Ethyl pyruvate: a novel treatment for sepsis
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh Medical School, 616 Scaife Hall, 3550 Terrace Street, Pittsburgh PA 15261, USA
    Curr Drug Targets 8:515-8. 2007
  10. doi request reprint Animal models of sepsis and its complications
    Mitchell P Fink
    Logical Therapeutics Inc, Waltham, Massachusetts, USA
    Kidney Int 74:991-3. 2008

Collaborators

Detail Information

Publications77

  1. pmc Bench-to-bedside review: Amelioration of acute renal impairment using ethyl pyruvate
    Michael C Reade
    Austin Hospital University of Melbourne, Heidelberg, Melbourne, Victoria, Australia
    Crit Care 9:556-60. 2005
    ..Ethyl pyruvate is a widely used as a food additive and was shown to be safe in phase I clinical trials. We suggest ethyl pyruvate warrants further evaluation in the management of acute renal impairment...
  2. pmc Equipment review: the success of early goal-directed therapy for septic shock prompts evaluation of current approaches for monitoring the adequacy of resuscitation
    Scott R Gunn
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Crit Care 9:349-59. 2005
    ..This article includes a response to the journal's Health Technology Assessment questionnaire by the manufacturer of the SCVO2 catheter...
  3. ncbi request reprint Hemigramicidin-TEMPO conjugates: novel mitochondria-targeted anti-oxidants
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States
    Biochem Pharmacol 74:801-9. 2007
    ..quot; One of these hemigramicidin-TEMPO conjugates, XJB-5-131, has been shown to ameliorate intestinal mucosal injury and prolong survival in rats subjected to lethal hemorrhage...
  4. ncbi request reprint Ethyl pyruvate: a novel anti-inflammatory agent
    M P Fink
    Departments of Critical Care Medicine, Pharmacology and Surgery, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA
    J Intern Med 261:349-62. 2007
    ..EP has been tested in human volunteers and shown to be safe at clinically relevant doses. It remains to be determined whether EP can be used successfully to treat human diseases...
  5. ncbi request reprint Intestinal epithelial hyperpermeability: update on the pathogenesis of gut mucosal barrier dysfunction in critical illness
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15260, USA
    Curr Opin Crit Care 9:143-51. 2003
    ....
  6. ncbi request reprint Hemigramicidin-TEMPO conjugates: novel mitochondria-targeted antioxidants
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Crit Care Med 35:S461-7. 2007
    ..Compounds like XJB-5-131 warrant further evaluation for the treatment of hemorrhagic shock as well as other acute conditions associated with increased mitochondrial production of ROS...
  7. pmc Pathophysiology of intensive care unit-acquired anemia
    Mitchell P Fink
    Anesthesiology and Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA
    Crit Care 8:S9-10. 2004
    ..Administration of recombinant human erythropoietin may stimulate erythropoiesis, increase hematocrit levels and hemoglobin concentration, and reduce the need for RBC transfusions...
  8. ncbi request reprint Research: advances in cell biology relevant to critical illness
    Mitchell P Fink
    Departments of Critical Care Medicine and Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Curr Opin Crit Care 10:279-91. 2004
    ..Other areas of important progress include improvements in our understanding of how inflammation causes derangements in epithelial structure and function and impairs cellular utilization of oxygen...
  9. ncbi request reprint Ethyl pyruvate: a novel treatment for sepsis
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh Medical School, 616 Scaife Hall, 3550 Terrace Street, Pittsburgh PA 15261, USA
    Curr Drug Targets 8:515-8. 2007
    ..Ethyl pyruvate warrants evaluation as a therapeutic agent for the treatment of sepsis in humans...
  10. doi request reprint Animal models of sepsis and its complications
    Mitchell P Fink
    Logical Therapeutics Inc, Waltham, Massachusetts, USA
    Kidney Int 74:991-3. 2008
    ..Recent experimental findings support this view and suggest that models of acute infection in mice with pre-existing renal dysfunction may be useful in the development pathway for new therapeutic agents for sepsis...
  11. ncbi request reprint Epithelial barrier dysfunction: a unifying theme to explain the pathogenesis of multiple organ dysfunction at the cellular level
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 616 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Crit Care Clin 21:177-96. 2005
    ....
  12. ncbi request reprint Mechanisms of organ dysfunction in critical illness: report from a Round Table Conference held in Brussels
    M P Fink
    Department of Critical Care Medicine, University of Pittsburgh Medical School, 616 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Intensive Care Med 28:369-75. 2002
  13. ncbi request reprint Increased iNOS activity is essential for intestinal epithelial tight junction dysfunction in endotoxemic mice
    Xiaonan Han
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA
    Shock 21:261-70. 2004
    ..production leading to altered expression and localization of key TJ proteins...
  14. ncbi request reprint Ethyl pyruvate reduces liver injury in a murine model of extrahepatic cholestasis
    Runkuan Yang
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Shock 22:369-75. 2004
    ..Ethyl pyruvate warrants further evaluation as an adjunctive treatment to ameliorate liver injury from extrahepatic biliary obstruction...
  15. pmc Anti-HMGB1 neutralizing antibody ameliorates gut barrier dysfunction and improves survival after hemorrhagic shock
    Runkuan Yang
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, PA 15621, USA
    Mol Med 12:105-14. 2006
    ..These data support the notion that HMGB1 is a mediator of HS/R-induced gut barrier dysfunction and suggest that anti-HMGB1 antibodies warrant further evaluation as a therapeutic to ameliorate the morbidity of HS/R in trauma patients...
  16. ncbi request reprint Ethyl pyruvate ameliorates intestinal epithelial barrier dysfunction in endotoxemic mice and immunostimulated caco-2 enterocytic monolayers
    Penny L Sappington
    Department of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261, USA
    J Pharmacol Exp Ther 304:464-76. 2003
    ..These data support the view that EP ameliorates cytokine- and/or LPS-induced derangements in intestinal epithelial barrier function...
  17. ncbi request reprint IL-6 is essential for development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice
    Runkuan Yang
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA
    Am J Physiol Gastrointest Liver Physiol 285:G621-9. 2003
    ..Collectively, these data support the view that expression of IL-6 is essential for the development of gut barrier dysfunction after HS/R...
  18. ncbi request reprint Increased iNOS activity is essential for pulmonary epithelial tight junction dysfunction in endotoxemic mice
    Xiaonan Han
    Department of Critical Care Medicine, 616 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15261, USA
    Am J Physiol Lung Cell Mol Physiol 286:L259-67. 2004
    ..These results suggest that decreased expression and mistargeting of TJ proteins in lung after systemic inflammation may be NO dependent...
  19. ncbi request reprint Evidence that glutathione depletion is a mechanism responsible for the anti-inflammatory effects of ethyl pyruvate in cultured lipopolysaccharide-stimulated RAW 264.7 cells
    Mingchen Song
    Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh Pennsylvania, USA
    J Pharmacol Exp Ther 308:307-16. 2004
    ..Moreover, the findings presented here suggest that an unusual combination of biochemical effects (inhibition of lipid peroxidation and GSH depletion) might account for the anti-inflammatory effects of EP...
  20. ncbi request reprint HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice
    Penny L Sappington
    Department of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261, USA
    Gastroenterology 123:790-802. 2002
    ..The proinflammatory actions of HMGB1 have been localized to a region of the molecule called the B box...
  21. ncbi request reprint Increased iNOS activity is essential for hepatic epithelial tight junction dysfunction in endotoxemic mice
    Xiaonan Han
    Deptartment of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Am J Physiol Gastrointest Liver Physiol 286:G126-36. 2004
    ....
  22. pmc Ethyl pyruvate decreases HMGB1 release and ameliorates murine colitis
    SHAIVAL H DAVE
    Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    J Leukoc Biol 86:633-43. 2009
    ..Ethyl pyruvate and other strategies to inhibit HMGB1 release and function represent promising interventions in chronic inflammatory diseases...
  23. pmc Treatment with a novel hemigramicidin-TEMPO conjugate prolongs survival in a rat model of lethal hemorrhagic shock
    Carlos A Macias
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Ann Surg 245:305-14. 2007
    ..We sought to develop a therapeutic agent that would permit prolongation of survival in rats subjected to lethal hemorrhagic shock (HS), even in the absence of resuscitation with asanguinous fluids or blood...
  24. ncbi request reprint Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock
    Runkuan Yang
    Department of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261, USA
    Am J Physiol Gastrointest Liver Physiol 283:G212-21. 2002
    ..These data support the view that resuscitation with REPS modulates the inflammatory response and decreases hepatocellular and gut mucosal injury in mice subjected to HS/R...
  25. ncbi request reprint Toll-like receptor-4 signaling mediates hepatic injury and systemic inflammation in hemorrhagic shock
    Jose M Prince
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Am Coll Surg 202:407-17. 2006
    ..We sought to determine the role of lipolysaccharide through use of CD14-/- mice...
  26. ncbi request reprint Dose-dependent effects of ethyl pyruvate in mice subjected to mesenteric ischemia and reperfusion
    Takashi Uchiyama
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Intensive Care Med 29:2050-8. 2003
    ..Ethyl pyruvate also has been shown to inhibit the expression of various pro-inflammatory cytokines in several animal models of critical illness, but dose-response relationships have not been investigated...
  27. ncbi request reprint Ethyl pyruvate ameliorates acute alcohol-induced liver injury and inflammation in mice
    Runkuan Yang
    Department of Critical Care Medicine, Pathology, and Surgery, University of Pittsburgh School of Medicine, PA 15261, USA
    J Lab Clin Med 142:322-31. 2003
    ..These data support the view that treatment with REPS ameliorates the hepatic inflammatory response and decreases hepatocellular injury in mice subjected to acute alcohol intoxication...
  28. ncbi request reprint Exogenous IL-6 inhibits acute inflammatory responses and prevents ischemia/reperfusion injury after intestinal transplantation
    Kei Kimizuka
    Thomas E Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA
    Am J Transplant 4:482-94. 2004
    ..These results show that IL-6 is effective in protecting the intestine from cold I/R injury by maintaining graft blood flow and reducing pro-inflammatory cytokine up-regulation and neutrophil infiltration...
  29. ncbi request reprint NAD+ ameliorates inflammation-induced epithelial barrier dysfunction in cultured enterocytes and mouse ileal mucosa
    Xiaonan Han
    Department of Critical Care Medicine, School of Medicine, University of Pittsburgh, 3550 Terrace St, Pittsburgh, PA 15261
    J Pharmacol Exp Ther 307:443-9. 2003
    ..Thus, extracellular NAD+ seems to ameliorate inflammation-induced intestinal epithelial barrier dysfunction by inhibiting NF-kappaB activation and increased NO. production...
  30. ncbi request reprint The ethyl pyruvate analogues, diethyl oxaloproprionate, 2-acetamidoacrylate, and methyl-2-acetamidoacrylate, exhibit anti-inflammatory properties in vivo and/or in vitro
    Penny L Sappington
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 616 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Biochem Pharmacol 70:1579-92. 2005
    ..Moreover, our findings suggest that esters with these general characteristics, perhaps because of their greater lipophilicity or electrophilicity, are more potent anti-inflammatory agents than are the parent carboxylates...
  31. ncbi request reprint Proinflammatory cytokines cause NO*-dependent and -independent changes in expression and localization of tight junction proteins in intestinal epithelial cells
    Xiaonan Han
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Shock 19:229-37. 2003
    ....
  32. ncbi request reprint Effect of hemorrhagic shock on gut barrier function and expression of stress-related genes in normal and gnotobiotic mice
    Runkuan Yang
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA
    Am J Physiol Regul Integr Comp Physiol 283:R1263-74. 2002
    ....
  33. ncbi request reprint Ethacrynic acid inhibits multiple steps in the NF-kappaB signaling pathway
    Yusheng Han
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Shock 23:45-53. 2005
    ....
  34. pmc The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Exp Med 201:1135-43. 2005
    ..Together, these results demonstrate that HMGB1 is an early mediator of injury and inflammation in liver I/R and implicates TLR4 as one of the receptors that is involved in the process...
  35. ncbi request reprint The role of RAGE in the pathogenesis of intestinal barrier dysfunction after hemorrhagic shock
    Kathleen G Raman
    Univ of Pittsburgh School of Medicine, 616 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 291:G556-65. 2006
    ..Circulating IL-10 levels were higher in rage(-/-) compared with rage(+/+) mice. These results suggest that activation of RAGE-dependent signaling is a key factor leading to gut mucosal barrier dysfunction after HS/R...
  36. ncbi request reprint The role of initial trauma in the host's response to injury and hemorrhage: insights from a correlation of mathematical simulations and hepatic transcriptomic analysis
    Claudio E Lagoa
    Department of Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Shock 26:592-600. 2006
    ..Mathematical simulations and DNA microarrays, both systems biology tools, may provide valuable insight into the complex global physiological interactions that occur in response to trauma and hemorrhagic shock...
  37. ncbi request reprint Bile modulates intestinal epithelial barrier function via an extracellular signal related kinase 1/2 dependent mechanism
    Runkuan Yang
    Department of Critical Care Medicine, School of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Intensive Care Med 31:709-17. 2005
    ..Proper expression of the tight junction (TJ) proteins ZO-1 and occludin is important for normal gut barrier function. We tested whether bile modulates intestinal epithelial ZO-1 and occludin expression...
  38. ncbi request reprint The phase 2 enzyme inducers ethacrynic acid, DL-sulforaphane, and oltipraz inhibit lipopolysaccharide-induced high-mobility group box 1 secretion by RAW 264.7 cells
    Meaghan E Killeen
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 615 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15261, USA
    J Pharmacol Exp Ther 316:1070-9. 2006
    ..7 cells. These data suggest that phase 2 inducers may exert anti-inflammatory effects by inhibiting secretion of the cytokine-like nuclear protein HMGB1...
  39. pmc In silico and in vivo approach to elucidate the inflammatory complexity of CD14-deficient mice
    Jose M Prince
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Mol Med 12:88-96. 2006
    ....
  40. ncbi request reprint The acute inflammatory response in diverse shock states
    Carson C Chow
    Department of Mathematics, University of Pittsburgh, Pittsburgh, Pensylvania 15261, USA
    Shock 24:74-84. 2005
    ....
  41. ncbi request reprint Ethyl pyruvate ameliorates distant organ injury in a murine model of acute necrotizing pancreatitis
    Runkuan Yang
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Crit Care Med 32:1453-9. 2004
    ..Herein, we used a murine model of acute pancreatitis to compare the effects of treatment with either Ringer's lactate solution or ethyl pyruvate solution on several physiologic and biochemical variables related to disease severity...
  42. ncbi request reprint Liposomal NAD(+) prevents diminished O(2) consumption by immunostimulated Caco-2 cells
    Abrar U Khan
    Department of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261, USA
    Am J Physiol Lung Cell Mol Physiol 282:L1082-91. 2002
    ..These data are consistent with the view that enterocytes exposed to proinflammatory cytokines consume less O(2) due to NAD(+)/NADH depletion secondary to activation of PARP by ONOO(-) or other oxidants...
  43. ncbi request reprint HMGB1 is secreted by immunostimulated enterocytes and contributes to cytomix-induced hyperpermeability of Caco-2 monolayers
    Shiguang Liu
    Department of Critical Care Medicine, Univ of Pittsburgh School of Medicine, 616 Scaife Hall, 3550 Terrace St, PA 15261, USA
    Am J Physiol Cell Physiol 290:C990-9. 2006
    ..Collectively, these data support the view that HMGB1 is secreted by immunostimulated enterocytes. This process may exacerbate inflammation-induced epithelial hyperpermeability via an autocrine feedback loop...
  44. ncbi request reprint Survival in a rat model of lethal hemorrhagic shock is prolonged following resuscitation with a small volume of a solution containing a drag-reducing polymer derived from aloe vera
    Carlos A Macias
    Department of Critical Care Medicine and Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    Shock 22:151-6. 2004
    ..0 +/- 1.0 vs. 6,3+/- 1.0 mL/kg/min) and Vco2 (9.0 +/- 1.1 vs. 6.0 +/- 1.0 mL/kg/min) after resuscitation. We conclude that resuscitation with a small volume of DRP prolongs survival in rats with lethal hemorrhagic shock...
  45. ncbi request reprint Systemic inflammation and remote organ injury following trauma require HMGB1
    Ryan M Levy
    Dept of Surgery, F 1200 PUH, Univ of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA
    Am J Physiol Regul Integr Comp Physiol 293:R1538-44. 2007
    ..Collectively, these data demonstrate a critical role for a TLR4-HMGB1 pathway in the initiation of systemic inflammation and end-organ injury following isolated peripheral tissue injury...
  46. pmc Prolonged treatment with N-acetylcystine delays liver recovery from acetaminophen hepatotoxicity
    Runkuan Yang
    Department of Critical Care Medicine, University of Pittsburgh Medical School, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Crit Care 13:R55. 2009
    ..Therefore, we hypothesize that prolonged treatment with NAC impairs liver regeneration in ALI induced by APAP...
  47. doi request reprint Bile high-mobility group box 1 contributes to gut barrier dysfunction in experimental endotoxemia
    Runkuan Yang
    Dept of Critical Care Medicine, Univ of Pittsburgh Medical School, 1055 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15261, USA
    Am J Physiol Regul Integr Comp Physiol 297:R362-9. 2009
    ..The increase in permeability and bacterial translocation was reversible following removal of HMGB1 from the endotoxemic rat bile. These findings document that bile HMGB1 mediates gut barrier dysfunction in experimental endotoxemia...
  48. doi request reprint Ethyl pyruvate ameliorates liver injury secondary to severe acute pancreatitis
    Runkuan Yang
    Department of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261, USA
    J Surg Res 153:302-9. 2009
    ..This study aims to elucidate the underlying mechanism of EP solution ameliorating SAP-induced liver injury and provide a new therapeutic agent to treat liver injury...
  49. ncbi request reprint Structural requirements for optimized delivery, inhibition of oxidative stress, and antiapoptotic activity of targeted nitroxides
    Jianfei Jiang
    Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA
    J Pharmacol Exp Ther 320:1050-60. 2007
    ..These new insights into the structure-activity relationships of nitroxide-peptide and -peptide isostere conjugates are instrumental for development of new mechanism-based therapeutically effective agents...
  50. doi request reprint Targeting mitochondria
    Adam T Hoye
    Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Acc Chem Res 41:87-97. 2008
    ....
  51. ncbi request reprint In silico models of acute inflammation in animals
    Yoram Vodovotz
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Shock 26:235-44. 2006
    ..Mathematical modeling may provide insights into the complex dynamics of acute inflammation in a manner that can be tested in vivo using many fewer animals than has been possible previously...
  52. pmc Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance
    RAJESH K ANEJA
    Department of Critical Care Medicine and Pediatrics, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    J Leukoc Biol 84:1326-34. 2008
    ..Taken together, these results suggest that extracellular HMGB1 induces LPS tolerance, and the RAGE receptor is required for this induction...
  53. ncbi request reprint Role of reactive oxygen and nitrogen species in acute respiratory distress syndrome
    Mitchell P Fink
    Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15261, USA
    Curr Opin Crit Care 8:6-11. 2002
    ..The most extensively studied compound in this regard is N -acetylcysteine; unfortunately, clinical trials with this compound in patients with acute respiratory distress syndrome have yielded disappointing results...
  54. ncbi request reprint Reactive oxygen species as mediators of organ dysfunction caused by sepsis, acute respiratory distress syndrome, or hemorrhagic shock: potential benefits of resuscitation with Ringer's ethyl pyruvate solution
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
    Curr Opin Clin Nutr Metab Care 5:167-74. 2002
    ..Ethyl pyruvate, a simple derivative of pyruvic acid, has been shown to be efficacious in several animal models of critical illness, and warrants further evaluation in this regard...
  55. ncbi request reprint Ringer's ethyl pyruvate solution: a novel resuscitation fluid for the treatment of hemorrhagic shock and sepsis
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA
    J Trauma 54:S141-3. 2003
    ..REPS warrants further evaluation for the resuscitation of patients with hemorrhagic shock...
  56. ncbi request reprint Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments
    Marina V Kameneva
    McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh, 3025 East Carson Street, Pittsburgh, PA 15203, USA
    Biorheology 41:53-64. 2004
    ..Our findings suggest that the drag-reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders...
  57. ncbi request reprint Ethyl pyruvate: a novel anti-inflammatory agent
    Mitchell P Fink
    Department of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA
    Crit Care Med 31:S51-6. 2003
    ....
  58. pmc Bench-to-bedside review: Cytopathic hypoxia
    Mitchell P Fink
    Department of Critical Care Medicine, Watson Chair in Surgery, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA
    Crit Care 6:491-9. 2002
    ....
  59. ncbi request reprint Resuscitation with Ringer's ethyl pyruvate solution prolongs survival and modulates plasma cytokine and nitrite/nitrate concentrations in a rat model of lipopolysaccharide-induced shock
    Ramesh Venkataraman
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    Shock 18:507-12. 2002
    ..These data support the view that delayed treatment with REPS modulates the inflammatory response to LPS, and prolongs survival time in a lethal model of endotoxic shock...
  60. ncbi request reprint Ethyl pyruvate provides durable protection against inflammation-induced intestinal epithelial barrier dysfunction
    Penny L Sappington
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Shock 20:521-8. 2003
    ..We conclude that EP provides durable protection against some of the deleterious effects of LPS or pro-inflammatory cytokines...
  61. ncbi request reprint Ethyl pyruvate inhibits nuclear factor-kappaB-dependent signaling by directly targeting p65
    Yusheng Han
    Department of Critical Care Medicine, 615 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    J Pharmacol Exp Ther 312:1097-105. 2005
    ..We conclude that some of the beneficial anti-inflammatory effects of ethyl pyruvate may be due to modification of p65, thereby inhibiting signaling via the NF-kappaB pathway...
  62. ncbi request reprint Resuscitation from hemorrhagic shock with Ringer's ethyl pyruvate solution improves survival and ameliorates intestinal mucosal hyperpermeability in rats
    Zakaria S Tawadrous
    Department of Critical Care Medicine, University of Pittsburgh Medical School, Pennsylvania 15261, USA
    Shock 17:473-7. 2002
    ..Resuscitation with REPS, a stable and nontoxic antioxidant solution, improves survival and ameliorates ileal mucosal permeability in a rat model of severe hemorrhagic shock...
  63. ncbi request reprint Critical care medicine training and certification for emergency physicians
    David T Huang
    Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Ann Emerg Med 46:217-23. 2005
    ..We therefore propose that all accreditation bodies work cooperatively to create a route to critical care medicine certification for emergency physicians who complete a critical care fellowship...
  64. ncbi request reprint Cytopathic hypoxia. Is oxygen use impaired in sepsis as a result of an acquired intrinsic derangement in cellular respiration?
    Mitchell P Fink
    Critical Care Medicine Division, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA
    Crit Care Clin 18:165-75. 2002
    ..Instead, the focus should be on developing pharmacologic strategies (e.g., isoform-selective iNOS or PARP inhibitors) to restore normal mitochondrial function and cellular energetics...
  65. ncbi request reprint Cytopathic hypoxia. Mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis
    M P Fink
    Division of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA
    Crit Care Clin 17:219-37. 2001
    ..Instead, the focus should be on developing pharmacologic strategies to restore normal mitochondrial function and cellular energetics...
  66. ncbi request reprint Cytopathic hypoxia in sepsis: a true problem?
    M P Fink
    University of Pittsburgh Medical School, Division of Critical Care Medicine, Anesthesiology and Critical Care Medicine, 3550 Terrace Street, Room 616 Scaife Hall, Pittsburgh, PA 15261, USA
    Minerva Anestesiol 67:290-1. 2001
    ....
  67. ncbi request reprint Ringer's ethyl pyruvate solution: a novel resuscitation fluid
    M P Fink
    University of Pittsburgh Medical Center, Division of Critical Care Medicine, 3550 Terrace Street, Room 616 Scaife Hall, Pittsburgh, PA 15261, USA
    Minerva Anestesiol 67:190-2. 2001
    ..We call this solution Ringer's Ethyl Pyruvate Solution (REPS), and have shown in preliminary studies that treatment with REPS can improve outcome in a variety of animal models of critical illness...
  68. ncbi request reprint A single intraperitoneal dose of carbon monoxide-saturated ringer's lactate solution ameliorates postoperative ileus in mice
    Atsunori Nakao
    Thomas E Starzl Transplantation Institute, Pennsylvania, USA
    J Pharmacol Exp Ther 319:1265-75. 2006
    ....
  69. ncbi request reprint The role of hepatic type 1 plasminogen activator inhibitor (PAI-1) during murine hemorrhagic shock
    Claudio E Lagoa
    Department of Surgery, University of Pittsburgh, S411 B South BST, Pittsburgh, PA 15261, USA
    Hepatology 42:390-9. 2005
    ..In conclusion, PAI-1 protein is a negative effector of hepatic damage after HS-R through its influence on classic regulators of hepatic growth, as opposed to its role in fibrinolysis...
  70. ncbi request reprint Ex vivo application of carbon monoxide in University of Wisconsin solution to prevent intestinal cold ischemia/reperfusion injury
    A Nakao
    Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pennsylvania, USA
    Am J Transplant 6:2243-55. 2006
    ..The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury...
  71. ncbi request reprint Ethyl pyruvate: a novel treatment for sepsis and shock
    M P Fink
    Department of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, USA
    Minerva Anestesiol 70:365-71. 2004
    ..The pharmacological basis for the anti-inflammatory effects of EP remains to be explained. It is plausible that EP mediates suppression of NF-KB activation and secretion of NO and of pro-inflammatory cytokines...
  72. pmc Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation
    Luis Ulloa
    Laboratory of Biomedical Science, North Shore LIJ Research Institute, 350 Community Drive, Manhasset, NY 11030, USA
    Proc Natl Acad Sci U S A 99:12351-6. 2002
    ..EP now warrants further evaluation as an experimental "rescue" therapeutic for sepsis and other potentially fatal systemic inflammatory disorders...
  73. ncbi request reprint Cytokines induce HIF-1 DNA binding and the expression of HIF-1-dependent genes in cultured rat enterocytes
    Marion Scharte
    Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitatsklinikum Munster, Munster, Germany
    Am J Physiol Gastrointest Liver Physiol 284:G373-84. 2003
    ..Proinflammatory cytokines activate the HIF-1 pathway and increase expression of glycolytic genes in nontransformed rat intestinal epithelial cells, largely through an NO.-independent mechanism...
  74. ncbi request reprint Proinflammatory cytokines increase the rate of glycolysis and adenosine-5'-triphosphate turnover in cultured rat enterocytes
    Soren Berg
    Department of Cardiothoracic Anesthesia SB, Linkoping University, Linkoping, Sweden
    Crit Care Med 31:1203-12. 2003
    ..Accordingly, we sought to use an in vitro "reductionist" model of sepsis to test the hypothesis that proinflammatory cytokines modulate ATP turnover rate...
  75. pmc Structural basis for the proinflammatory cytokine activity of high mobility group box 1
    Jianhua Li
    Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute, 350 Community Drive, Manhasset, NY 11030, USA
    Mol Med 9:37-45. 2003
    ..These results indicate that a proinflammatory domain of HMGB1 maps to the highly conserved DNA-binding B box, making this primary sequence a suitable target in the design of therapeutics...
  76. ncbi request reprint Red blood cell physiology in critical illness
    Marion Scharte
    Klinik und Poliklinik für Anästhesiologie und operativ Intensivmedizin, Universitatsklinikum Munster, Muenster, Germany
    Crit Care Med 31:S651-7. 2003
    ..This review discusses these changes in red blood cell physiology, emphasizing the pathogenesis of anemia in intensive care unit patients...
  77. ncbi request reprint Ethyl pyruvate improves systemic and hepatosplanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia
    Balázs Hauser
    Sektion Anasthesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinikum, Ulm, Germany
    Crit Care Med 33:2034-42. 2005
    ..To investigate the systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of delayed treatment with ethyl pyruvate in a long-term porcine model of hyperdynamic endotoxemia...