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Published in: Intensive Care Medicine 12/2011

01-12-2011 | Experimental

A metabolomic approach for diagnosis of experimental sepsis

Authors: José L. Izquierdo-García, Nicolás Nin, Jesús Ruíz-Cabello, Yeny Rojas, Marta de Paula, Sonia López-Cuenca, Luis Morales, Leticia Martínez-Caro, Pilar Fernández-Segoviano, Andrés Esteban, José A. Lorente

Published in: Intensive Care Medicine | Issue 12/2011

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Abstract

Background

The search for reliable diagnostic biomarkers of sepsis remains necessary. Assessment of global metabolic profiling using quantitative nuclear magnetic resonance (NMR)-based metabolomics offers an attractive modern methodology for fast and comprehensive determination of multiple circulating metabolites and for defining the metabolic phenotype of sepsis.

Objective

To develop a novel NMR-based metabolomic approach for diagnostic evaluation of sepsis.

Methods

Male Sprague–Dawley rats (weight 325–375 g) underwent cecal ligation and puncture (n = 14, septic group) or sham procedure (n = 14, control group) and 24 h later were euthanized. Lung tissue, bronchoalveolar lavage (BAL) fluid, and serum samples were obtained for 1H NMR and high-resolution magic-angle spinning analysis. Unsupervised principal components analysis was performed on the processed spectra, and a predictive model for diagnosis of sepsis was constructed using partial least-squares discriminant analysis.

Results

NMR-based metabolic profiling discriminated characteristics between control and septic rats. Characteristic metabolites changed markedly in septic rats as compared with control rats: alanine, creatine, phosphoethanolamine, and myoinositol concentrations increased in lung tissue; creatine increased and myoinositol decreased in BAL fluid; and alanine, creatine, phosphoethanolamine, and acetoacetate increased whereas formate decreased in serum. A predictive model for diagnosis of sepsis using these metabolites classified cases with sensitivity and specificity of 100%.

Conclusions

NMR metabolomic analysis is a potentially useful technique for diagnosis of sepsis. The concentrations of metabolites involved in energy metabolism and in the inflammatory response change in this model of sepsis.
Literature
1.
go back to reference Esteban A, Frutos-Vivar F, Ferguson ND, Peñuelas O, Lorente JA, Gordo F, Honrubia T, Algora A, Bustos A, García G, Rodríguez Diaz-Regañón I, Ruiz de Luna R (2007) Sepsis incidence and outcome: contrasting the intensive care unit with the hospital ward. Crit Care Med 35:1284–1289PubMedCrossRef Esteban A, Frutos-Vivar F, Ferguson ND, Peñuelas O, Lorente JA, Gordo F, Honrubia T, Algora A, Bustos A, García G, Rodríguez Diaz-Regañón I, Ruiz de Luna R (2007) Sepsis incidence and outcome: contrasting the intensive care unit with the hospital ward. Crit Care Med 35:1284–1289PubMedCrossRef
2.
go back to reference Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated cost of care. Crit Care Med 29:1303–1310PubMedCrossRef Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated cost of care. Crit Care Med 29:1303–1310PubMedCrossRef
3.
go back to reference Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, Mercier JC, Offenstadt G, Régnier B (1995) Incidence, risk factors, and outcome of severe sepsis study in intensive care units: a multicenter prospective study in intensive care units. JAMA 274:968–974PubMedCrossRef Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, Mercier JC, Offenstadt G, Régnier B (1995) Incidence, risk factors, and outcome of severe sepsis study in intensive care units: a multicenter prospective study in intensive care units. JAMA 274:968–974PubMedCrossRef
4.
go back to reference Nin N, Lorente JA, Ortiz-Leyba C, Valenzuela F, Baigorri F, López A, Sánchez M, Raurich JM, Ibáñez J (2005) Estudio multicéntrico sobre la asociación entre variables relacionadas con la resucitación y la mortalidad en la sepsis grave. Med Intensiva 29:212–218CrossRef Nin N, Lorente JA, Ortiz-Leyba C, Valenzuela F, Baigorri F, López A, Sánchez M, Raurich JM, Ibáñez J (2005) Estudio multicéntrico sobre la asociación entre variables relacionadas con la resucitación y la mortalidad en la sepsis grave. Med Intensiva 29:212–218CrossRef
5.
go back to reference Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2002. N Engl J Med 348:1546–1554PubMedCrossRef Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2002. N Engl J Med 348:1546–1554PubMedCrossRef
6.
go back to reference Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med 34:17–60PubMedCrossRef Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med 34:17–60PubMedCrossRef
7.
go back to reference Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J (2004) Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 39:206–217PubMedCrossRef Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J (2004) Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 39:206–217PubMedCrossRef
8.
go back to reference Hinkelbein J, Feldmann RE Jr, Schubert C, Peterka A, Schelshorn D, Maurer MH, Kalenka A (2009) Alterations in rat serum proteome and metabolome as putative disease markers in sepsis. J Trauma 66:1065–1075PubMedCrossRef Hinkelbein J, Feldmann RE Jr, Schubert C, Peterka A, Schelshorn D, Maurer MH, Kalenka A (2009) Alterations in rat serum proteome and metabolome as putative disease markers in sepsis. J Trauma 66:1065–1075PubMedCrossRef
9.
go back to reference Hinkelbein J, Kalenka A, Schubert C, Peterka A, Feldmann RE Jr (2010) Proteome and metabolome alterations in heart and liver indicate compromised energy production during sepsis. Prot Pept Lett 17:18–31CrossRef Hinkelbein J, Kalenka A, Schubert C, Peterka A, Feldmann RE Jr (2010) Proteome and metabolome alterations in heart and liver indicate compromised energy production during sepsis. Prot Pept Lett 17:18–31CrossRef
10.
go back to reference Hinkelbein J, Feldmann RE Jr, Peterka A, Schubert C, Schelshorn D, Maurer MH, Kalenka A (2007) Alterations in cerebral metabolomics and proteomic expression during sepsis. Curr Neurovasc Res 4:280–288PubMedCrossRef Hinkelbein J, Feldmann RE Jr, Peterka A, Schubert C, Schelshorn D, Maurer MH, Kalenka A (2007) Alterations in cerebral metabolomics and proteomic expression during sepsis. Curr Neurovasc Res 4:280–288PubMedCrossRef
11.
go back to reference Bales JR, Higham DP, Howe I, Nicholson JK, Sadler PJ (1984) Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem 30:426–432PubMed Bales JR, Higham DP, Howe I, Nicholson JK, Sadler PJ (1984) Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem 30:426–432PubMed
12.
go back to reference Gartland KP, Sanins SM, Nicholson JK, Sweatman BC, Beddell CR, Lindon JC (1990) Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data. NMR Biomed 3:166–172PubMedCrossRef Gartland KP, Sanins SM, Nicholson JK, Sweatman BC, Beddell CR, Lindon JC (1990) Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data. NMR Biomed 3:166–172PubMedCrossRef
13.
go back to reference Nicholson JK, Wilson ID (1989) High-resolution proton magnetic-resonance spectroscopy of biological-fluids. Prog Nucl Magn Reson Spectrosc 21:449–501CrossRef Nicholson JK, Wilson ID (1989) High-resolution proton magnetic-resonance spectroscopy of biological-fluids. Prog Nucl Magn Reson Spectrosc 21:449–501CrossRef
14.
go back to reference Lindon JC, Nicholson JK, Everett JR (1999) NMR spectroscopy of biofluids, annual reports on nmr spectroscopy, vol 38. Academic, San Diego, pp 1–88 Lindon JC, Nicholson JK, Everett JR (1999) NMR spectroscopy of biofluids, annual reports on nmr spectroscopy, vol 38. Academic, San Diego, pp 1–88
15.
go back to reference Bollard ME, Garrod S, Holmes E, Lincoln JC, Humpfer E, Spraul M, Nicholson JK (2000) High-resolution H-1 and H-1-C-13 magic angle spinning NMR spectroscopy of rat liver. Magn Reson Med 44:201–207PubMedCrossRef Bollard ME, Garrod S, Holmes E, Lincoln JC, Humpfer E, Spraul M, Nicholson JK (2000) High-resolution H-1 and H-1-C-13 magic angle spinning NMR spectroscopy of rat liver. Magn Reson Med 44:201–207PubMedCrossRef
16.
go back to reference Garrod S, Humpfer E, Spraul M, Connor SC, Polley S, Connelly J, Lindon JC, Nicholson JK, Holmes E (1999) High-resolution magic angle spinning H-1 NMR spectroscopic studies on intact rat renal cortex and medulla. Magn Reson Med 41:1108–1118PubMedCrossRef Garrod S, Humpfer E, Spraul M, Connor SC, Polley S, Connelly J, Lindon JC, Nicholson JK, Holmes E (1999) High-resolution magic angle spinning H-1 NMR spectroscopic studies on intact rat renal cortex and medulla. Magn Reson Med 41:1108–1118PubMedCrossRef
17.
go back to reference Cheng LL, Chang IW, Smith BL, Gonzalez RG (1998) Evaluating human breast ductal carcinomas with high-resolution magic-angle spinning proton magnetic resonance spectroscopy. J Magn Reson 135:194–202PubMedCrossRef Cheng LL, Chang IW, Smith BL, Gonzalez RG (1998) Evaluating human breast ductal carcinomas with high-resolution magic-angle spinning proton magnetic resonance spectroscopy. J Magn Reson 135:194–202PubMedCrossRef
18.
go back to reference Saude EJ, Lacy P, Musat-Marcu S, Mayes DC, Bagu J, Man SF, Sykes BD, Moqbel R (2004) NMR analysis of neutrophil activation in sputum samples from patients with cystic fibrosis. Magn Reson Med 52:807–814PubMedCrossRef Saude EJ, Lacy P, Musat-Marcu S, Mayes DC, Bagu J, Man SF, Sykes BD, Moqbel R (2004) NMR analysis of neutrophil activation in sputum samples from patients with cystic fibrosis. Magn Reson Med 52:807–814PubMedCrossRef
19.
go back to reference Saude EJ, Obiefuna IP, Somorjai RL, Ajamian F, Skappak C, Ahmad T, Dolenko BK, Sykes BD, Moqbel R, Adamko DJ (2009) Metabolomic biomarkers in a model of asthma exacerbation urine nuclear magnetic resonance. Am J Respir Crit Care Med 179:25–34PubMedCrossRef Saude EJ, Obiefuna IP, Somorjai RL, Ajamian F, Skappak C, Ahmad T, Dolenko BK, Sykes BD, Moqbel R, Adamko DJ (2009) Metabolomic biomarkers in a model of asthma exacerbation urine nuclear magnetic resonance. Am J Respir Crit Care Med 179:25–34PubMedCrossRef
20.
go back to reference Izquierdo-García J, del Puerto-Nevado L, Peces-Barba G, Pérez-Rial S, Heili S, Villa P, Castejón D, González-Mangado N, Ruiz-Cabello J (2009) A metabonomic approach to evaluate COPD in a model of cigarette smoke exposure in mice. Metabolomics. 1–10 Izquierdo-García J, del Puerto-Nevado L, Peces-Barba G, Pérez-Rial S, Heili S, Villa P, Castejón D, González-Mangado N, Ruiz-Cabello J (2009) A metabonomic approach to evaluate COPD in a model of cigarette smoke exposure in mice. Metabolomics. 1–10
21.
go back to reference Xu PB, Lin ZY, Meng HB, Yan SK, Yang Y, Liu XR, Li JB, Deng XM, Zhang WD (2008) A metabonomic approach to early prognostic evaluation of experimental sepsis. J Infect 56:474–481PubMedCrossRef Xu PB, Lin ZY, Meng HB, Yan SK, Yang Y, Liu XR, Li JB, Deng XM, Zhang WD (2008) A metabonomic approach to early prognostic evaluation of experimental sepsis. J Infect 56:474–481PubMedCrossRef
22.
go back to reference Lin ZY, Xu PB, Yan SK, Meng HB, Yang GJ, Dai WX, Liu XR, Li JB, Deng XM, Zhang WD (2009) A metabonomic approach to early prognostic evaluation of experimental sepsis by 1H NMR and pattern recognition. NMR Biomed 22:601–608PubMedCrossRef Lin ZY, Xu PB, Yan SK, Meng HB, Yang GJ, Dai WX, Liu XR, Li JB, Deng XM, Zhang WD (2009) A metabonomic approach to early prognostic evaluation of experimental sepsis by 1H NMR and pattern recognition. NMR Biomed 22:601–608PubMedCrossRef
23.
go back to reference Mao H, Wang H, Wang B, Liu X, Gao H, Xu M, Zhao H, Deng X, Lin D (2009) Systemic metabolic changes of traumatic critically ill patients revealed by an NMR-based metabonomic approach. J Proteome Res 8:5423–5430PubMedCrossRef Mao H, Wang H, Wang B, Liu X, Gao H, Xu M, Zhao H, Deng X, Lin D (2009) Systemic metabolic changes of traumatic critically ill patients revealed by an NMR-based metabonomic approach. J Proteome Res 8:5423–5430PubMedCrossRef
24.
go back to reference Singleton KD, Wischmeyer PE (2003) Distance of cecum ligated influences mortality, tumor necrosis factor-alpha and interleukin-6-expression following cecal ligation and puncture in the rat. Eur Surg Res 35:486–491PubMedCrossRef Singleton KD, Wischmeyer PE (2003) Distance of cecum ligated influences mortality, tumor necrosis factor-alpha and interleukin-6-expression following cecal ligation and puncture in the rat. Eur Surg Res 35:486–491PubMedCrossRef
25.
go back to reference Rittirsch D, Hoesel LM, Ward PA (2007) The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol 81:137–143PubMedCrossRef Rittirsch D, Hoesel LM, Ward PA (2007) The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol 81:137–143PubMedCrossRef
26.
go back to reference Broadhurst D, Kell D (2006) Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics 2:171–196CrossRef Broadhurst D, Kell D (2006) Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics 2:171–196CrossRef
27.
go back to reference Nin N, Lorente JA, Fernández-Segoviano P, De Paula M, Ferruelo A, Esteban A (2009) High-tidal volume ventilation aggravates sepsis-induced multiorgan dysfunction in a dexamethasone-inhibitable manner. Shock 31:429–434PubMedCrossRef Nin N, Lorente JA, Fernández-Segoviano P, De Paula M, Ferruelo A, Esteban A (2009) High-tidal volume ventilation aggravates sepsis-induced multiorgan dysfunction in a dexamethasone-inhibitable manner. Shock 31:429–434PubMedCrossRef
28.
go back to reference Xi Y, Rocke DM (2008) Baseline correction for NMR spectroscopic metabolomics data analysis. BMC Bioinformatics 9:324PubMedCrossRef Xi Y, Rocke DM (2008) Baseline correction for NMR spectroscopic metabolomics data analysis. BMC Bioinformatics 9:324PubMedCrossRef
29.
go back to reference Izquierdo-García JL, Rodríguez I, Kyriazis A, Villa P, Barreiro P, Desco M, Ruíz-Cabello J (2009) A novel R-package graphic user interface for the analysis of metabonomic profiles. BMC Bioinformatics 10:363PubMedCrossRef Izquierdo-García JL, Rodríguez I, Kyriazis A, Villa P, Barreiro P, Desco M, Ruíz-Cabello J (2009) A novel R-package graphic user interface for the analysis of metabonomic profiles. BMC Bioinformatics 10:363PubMedCrossRef
30.
go back to reference R: A Language and Environment for Statistical Computing (2010) The R foundation for statistical computing R: A Language and Environment for Statistical Computing (2010) The R foundation for statistical computing
31.
go back to reference Holmes E, Foxall PJD, Nicholson JK, Neild GH, Brown SM, Beddell CR, Sweatman BC, Rahr E, Lindon JC, Spraul M, Neidig P (1994) Automatic data reduction and pattern recognition methods for analysis of 1H nuclear magnetic resonance spectra of human urine from normal and pathological states. Anal Biochem 220:284–296PubMedCrossRef Holmes E, Foxall PJD, Nicholson JK, Neild GH, Brown SM, Beddell CR, Sweatman BC, Rahr E, Lindon JC, Spraul M, Neidig P (1994) Automatic data reduction and pattern recognition methods for analysis of 1H nuclear magnetic resonance spectra of human urine from normal and pathological states. Anal Biochem 220:284–296PubMedCrossRef
32.
go back to reference Hotelling H (1933) Analysis of a complex of statistical variables into principal components. J Educ Psychol 24:417–441CrossRef Hotelling H (1933) Analysis of a complex of statistical variables into principal components. J Educ Psychol 24:417–441CrossRef
33.
go back to reference Kramer R (1998) Chemometric techniques for quantitative analysis. Marcel Dekker, New YorkCrossRef Kramer R (1998) Chemometric techniques for quantitative analysis. Marcel Dekker, New YorkCrossRef
34.
go back to reference Ding B, Gentleman R (2005) Classification using generalized partial least squares. J Comput Graph Stat 14:280–298CrossRef Ding B, Gentleman R (2005) Classification using generalized partial least squares. J Comput Graph Stat 14:280–298CrossRef
35.
go back to reference Martínez-Bisbal MC, Martí-Bonmati L, Piquer J, Revert A, Ferrer P, Llacer JL, Piotto M, Assemat O, Celda B (2004) 1H and 13C HR-MAS spectroscopy of intact biopsy samples ex vivo and in vivo 1H MRS study of human high grade gliomas. NMR Biomed 17:191–205PubMedCrossRef Martínez-Bisbal MC, Martí-Bonmati L, Piquer J, Revert A, Ferrer P, Llacer JL, Piotto M, Assemat O, Celda B (2004) 1H and 13C HR-MAS spectroscopy of intact biopsy samples ex vivo and in vivo 1H MRS study of human high grade gliomas. NMR Biomed 17:191–205PubMedCrossRef
36.
go back to reference Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13:129–153PubMedCrossRef Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13:129–153PubMedCrossRef
37.
go back to reference Sitter B, Sonnewald U, Spraul M, Fjosne HE, Gribbestad IS (2002) High-resolution magic angle spinning MRS of breast cancer tissue. NMR Biomed 15:327–337PubMedCrossRef Sitter B, Sonnewald U, Spraul M, Fjosne HE, Gribbestad IS (2002) High-resolution magic angle spinning MRS of breast cancer tissue. NMR Biomed 15:327–337PubMedCrossRef
38.
go back to reference Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S, Mandal R, Sinelnikov I, Xia J, Jia L, Cruz JA, Lim E, Sobsey CA, Shrivastava S, Huang P, Liu P, Fang L, Peng J, Fradette R, Cheng D, Tzur D, Clements M, Lewis A, De Souza A, Zuniga A, Dawe M, Xiong Y, Clive D, Greiner R, Nazyrova A, Shaykhutdinov R, Li L, Vogel HJ, Forsythe I (2009) HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res 37:D603–D610PubMedCrossRef Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S, Mandal R, Sinelnikov I, Xia J, Jia L, Cruz JA, Lim E, Sobsey CA, Shrivastava S, Huang P, Liu P, Fang L, Peng J, Fradette R, Cheng D, Tzur D, Clements M, Lewis A, De Souza A, Zuniga A, Dawe M, Xiong Y, Clive D, Greiner R, Nazyrova A, Shaykhutdinov R, Li L, Vogel HJ, Forsythe I (2009) HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res 37:D603–D610PubMedCrossRef
39.
go back to reference Gore DC, Jahoor F, Hibbert J, DeMaria EJ (1995) Except for alanine, muscle protein catabolism is not influenced by alterations in glucose metabolism during sepsis. Arch Surg 130:1171–1176PubMed Gore DC, Jahoor F, Hibbert J, DeMaria EJ (1995) Except for alanine, muscle protein catabolism is not influenced by alterations in glucose metabolism during sepsis. Arch Surg 130:1171–1176PubMed
40.
go back to reference Bolton CF (1996) Sepsis and the systemic inflammatory response syndrome: neuromuscular manifestations. Crit Care Med 24:1408–1416PubMedCrossRef Bolton CF (1996) Sepsis and the systemic inflammatory response syndrome: neuromuscular manifestations. Crit Care Med 24:1408–1416PubMedCrossRef
41.
go back to reference Vulimiri SV, Misra M, Hamm JT, Mitchell M, Berger A (2009) Effects of mainstream cigarette smoke on the global metabolome of human lung epithelial cells. Chem Res Toxicol 22:492–503PubMedCrossRef Vulimiri SV, Misra M, Hamm JT, Mitchell M, Berger A (2009) Effects of mainstream cigarette smoke on the global metabolome of human lung epithelial cells. Chem Res Toxicol 22:492–503PubMedCrossRef
42.
go back to reference Mervyn S, Vincenzo De S, Domenico V, William J (2004) Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet 364:545–548CrossRef Mervyn S, Vincenzo De S, Domenico V, William J (2004) Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet 364:545–548CrossRef
43.
go back to reference McClay JL, Adkins DE, Isern NG, O’Connell TM, Wooten JB, Zedler BK, Dasika MS, Webb BT, Webb-Robertson BJ, Pounds JG, Murrelle EL, Leppert MF, van den Oord EJ (2010) 1H nuclear magnetic resonance metabolomics analysis identifies novel urinary biomarkers for lung function. J Proteome Res 6:3083–3090CrossRef McClay JL, Adkins DE, Isern NG, O’Connell TM, Wooten JB, Zedler BK, Dasika MS, Webb BT, Webb-Robertson BJ, Pounds JG, Murrelle EL, Leppert MF, van den Oord EJ (2010) 1H nuclear magnetic resonance metabolomics analysis identifies novel urinary biomarkers for lung function. J Proteome Res 6:3083–3090CrossRef
44.
go back to reference Sotoda Y, Negoro M, Wakabayashi I (2002) Involvement of decreased myo-inositol transport in lipopolysaccharide-induced depression of phosphoinositide hydrolysis in vascular smooth muscle. FEBS Lett 519:227–230PubMedCrossRef Sotoda Y, Negoro M, Wakabayashi I (2002) Involvement of decreased myo-inositol transport in lipopolysaccharide-induced depression of phosphoinositide hydrolysis in vascular smooth muscle. FEBS Lett 519:227–230PubMedCrossRef
Metadata
Title
A metabolomic approach for diagnosis of experimental sepsis
Authors
José L. Izquierdo-García
Nicolás Nin
Jesús Ruíz-Cabello
Yeny Rojas
Marta de Paula
Sonia López-Cuenca
Luis Morales
Leticia Martínez-Caro
Pilar Fernández-Segoviano
Andrés Esteban
José A. Lorente
Publication date
01-12-2011
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 12/2011
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-011-2359-1

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