Searching for NF-κB-based treatments of ischemia reperfusion injury

Journal of Investigative Surgery

Volumn 22, Issue 4, 2009, Pages 301-315

  Latanich, Christopher A ^a,b   Toledo Pereyra, Luis H ^a  

^a MICHIGAN STATE UNIVERSITY   (United States)

^b MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

Ischemia reperfusion injury; NF B; Pharmacology; Preconditioning; Prevention; Reperfusion; Transplantation; Treatment

Indexed keywords

ADENOVIRUS VECTOR; BAY 65 1942; CYTOKINE RECEPTOR ANTAGONIST; DEHYDROXYMETHYLEPOXYQUINOMICIN; ERITORAN; ETANERCEPT; GLUCAN PHOSPHATE; I KAPPA B; IMD 0354; IMMUNOGLOBULIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; LACTACYSTIN; LACTACYSTIN BETA LACTONE; OLIGODEOXYNUCLEOTIDE DERIVATIVE; PHOSPHATE; PROTEASOME INHIBITOR; TOLL LIKE RECEPTOR; TRANSCRIPTION FACTOR REL; TUMOR NECROSIS FACTOR RECEPTOR; UNCLASSIFIED DRUG; HYPOXIA INDUCIBLE FACTOR 1; IMMUNOGLOBULIN G; OLIGODEOXYRIBONUCLEOTIDE; PROTEASOME; TNFR FC FUSION PROTEIN; TNFR-FC FUSION PROTEIN;

BRAIN INFARCTION; BRAIN INFARCTION SIZE; CELL PROTECTION; DRUG MECHANISM; DRUG TARGETING; GENE THERAPY; HEART INFARCTION SIZE; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INFLAMMATION; ISCHEMIA; ISCHEMIA REPERFUSION INJURY; ISCHEMIC PRECONDITIONING; KIDNEY ARTERY STENOSIS; NONHUMAN; PRIORITY JOURNAL; REPERFUSION INJURY; RESPIRATORY DISTRESS; REVIEW; SUPERIOR MESENTERIC ARTERY OBSTRUCTION; TRANSCRIPTION INITIATION; ANIMAL; DRUG ANTAGONISM; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; GENE THERAPY; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; I-KAPPA B PROTEINS; IMMUNOGLOBULIN G; ISCHEMIC PRECONDITIONING; NF-KAPPA B; OLIGODEOXYRIBONUCLEOTIDES; PROTEASOME ENDOPEPTIDASE COMPLEX; RECEPTORS, TUMOR NECROSIS FACTOR; REPERFUSION INJURY; TOLL-LIKE RECEPTORS;

EID: 73949137394     PISSN: 08941939     EISSN: 15210553     Source Type: Journal    
DOI: 10.1080/08941930903040155     Document Type: Review

References (114)

1. Kung HC, Hoyert DL, Xu JQ, et al. Deaths: Final Data for 2005. NationalVital Statistics Reports; vol.56, no.10. Hyattsville,MD: National Center for Health Statistics; 2008.
2. Sen R. Control of B lymphocyte apoptosis by the transcription factor NF-κB. Immunity. 2006;25:871-883.
3. Li Q, Verma IM. NF-κB regulation in the immune system. Nat Rev Immunol. 2002;2:725-734.
4. Cummins EP, Berra E, ComerfordKM, et al. Prolyl hydroxylase-1 negatively regulates IκBkinase-β, giving insight into hypoxiainduced NF?B activity. Proc Natl Acad Sci. 2006;103(48):18154-18159.
5. BelAiba RS, Bonello S, Zähringer C, et al. Hypoxia upregulates hypoxia-inducible factor-1α transcription by involving phosphatidylinositol 3-kinase and nuclear factor κB in pulmonary artery smooth muscle cells. Mol Biol Cell. 2007;18:4691-4697.
6. Uden P, Kenneth NS, Rocha S. Regulation of hypoxia-inducible factor-1α by NF-κB. Biochem J. 2008;412:477-484.
7. SemenzaGL. HIF-1,O2, and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell. 2001;107:1-3.
8. Walmsley SR, Print C, Farahi N, et al. Hypoxia-induced neutrophil survival ismediated by HIF-1α-dependent NF-κB activity. J Exp Med. 2005;201(1):105-115.
9. Rius J, Guma M, Schachtrup C, et al. NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α . Nature. 2008;435:807-811.
10. Cockman ME, Lancaster DE, Stolze IP, et al. Posttranslational hydroxylation of ankyrin repeats in IκB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH). Proc Natl Acad Sci. 2006;103(40):14767-14772.
11. Görlach A, Bonello S. The cross-talk between NF-κB and HIF-1: further evidence for a significant liaison. Biochem J. 2008;412:e17-e19.
12. Lawrence T, Gilroy DW, Colville-Nash PR, et al. Possible new role for NF-κB in the resolution of inflammation. Nat Med. 2001;7(12):1291-1297.
13. May MJ, Ghosh S. Rel/NF-κB and IκB proteins: an overview. Semin Cancer Biol. 1997;8:63-73.
14. Ghosh S, May MJ, Kopp EB. NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Ann Rev Immunol. 1998;16:225-260.
15. Bonizzi G, Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004;25(6):280-288.
16. Shimamoto A, Pohlman TH, Shomura S, et al. Toll-like receptor 4 mediates lung ischemia-reperfusion injury. Ann Thorac Surg. 2006;82:2017-2023.
17. Klune JR, Billiar TR, Tsung A. HMGB1 preconditioning: therapeutic application for a danger signal? J Leukocyte Biol. 2008;83:558-563.
18. Pahl HL.Activators and target genes ofRel/NF-κBtranscription factors. Oncogene. 1999;18:6853-6866.
19. Chariot A. 20 years of NF-κB. Biochem Pharmacol. 2006;72:1051-1053.
20. Karin M, Lin A. NF-κB at the crossroads of life and death. Nat Immunol. 2002;3(3):221-226.
21. Rami A, Bechmann I, Stehle JH. Exploiting endogenous antiapoptotic proteins for novel therapeutic strategies in cerebral ischemia. Prog Neurobiol. 2008;85(3):273-296.
22. Hatada EN, Krappmann D, Scheidereit C. NF-κB and the innate immune response. Curr Opin Immunol. 2000;12:52-58.
23. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu Rev Immunol. 2000;18:621-663.
24. Häcker H, Karin M. Is NF-κB2/p100 a direct activator of programmed cell death? Cancer Cell. 2002;2(6):431-433.
25. Xiao G, Harhaj EW, Sun SC. NF-κB-inducing kinase regulates the processing of NF-κB2 p100. Mol Cell. 2001;7:401-409.
26. Whiteside ST, Epinat JC, Rice NR, Isräel A. I kappa B epsilon, a novel member of the IκB family, controls RelA and cRel NF-κB activity. EMBO J. 1997;16(6):1413-1426.
27. Dejardin E, Droin NM, Delhase M, et al. The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways. Immunity. 2002;17(4):525-535.
28. Tergaonkar V, Perkins ND. p53 and NF-κB crosstalk: IKKα tips the balance. Mol Cell. 2007;26:158-159.
29. Tergaonkar V, Bottero V, IkawaM, et al. IκB kinase-independent IκBα degradation pathway; functional NF-κB activity and implications for cancer therapy. Mol Cell Biol. 2003;23(22):8070-8083.
30. KarinM. The IκB kinase (IKK) complex as a critical regulator of immune responses. Int Congr Ser. 2005;1285:97-103.
31. Chen L, FischleW,Verdin E, et al. Duration of nuclear NF-κBaction regulated by reversible acetylation. Science. 2001;293:1653-1657.
32. Sun SC. Deubiquitylation and regulation of the immune response. Nat Rev Immunol. 2008;8:501-511.
33. Ghosh S, Karin M. Missing pieces in the NF-κB puzzle. Cell. 2002;109:s81-s96.
34. BergheWV,NdlovuMN, Hoya-Arias R, et al.Keeping upNF-κB appearances: epigenetic control of immunity or inflammationtriggered epigenetics. Biochem Pharmacol. 2006;72:1114-1131.
35. Iida H, Schmeichel AM, Wang Y, et al. Orchestration of the inflammatory response in ischemia-reperfusion injury. J Peripher Nerv Syst. 2007;12:131-138.
36. Ryan KM, Ernst MK, Rice NR, et al. Role of NF-κB in p53-mediated programmed cell death. Nature. 2000;404:892-897.
37. Aggarwal BB. Apoptosis and nuclear factor-κB: a tale of association and dissociation. Biochem Pharmacol. 2000;60:1033-1039.
38. KarinM. The beginning of the end: IκB kinase (IKK) and NF-κB activation. J Biol Chem. 1999;274(39):27339-27342.
39. Thanos D, Maniatis T. NF-κB: a lesson in family values. Cell. 1995;80:529-532.
40. Thompson JE, Roderick JP, Erdjument-Bromage H, et al. IκB-β regulates the persistent response in a biphasic activation of NF-κB. Cell. 1995;80:573-582.
41. Malek S, Chen Y, Huxford T, et al. IκBα, but not IκBα, functions as a classical cytoplasmic inhibitor of NF-κB dimers bymasking both NF-κB nuclear localization sequences in resting cells. J Biol Chem. 2001;276(48):45225-45235.
42. Cheng JD, Ryseck RP, Attar RM, et al. Functional redundancy of the nuclear factor αB inhibitors IκBα and IκBα. J Exp Med. 1998;188(6):1055-1062.
43. Bonizzi G, Karin M. The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004;25(6)280-288.
44. Yamamoto Y, Gaynor RB. IκB kinases: key regulators of the NF-κB pathway. Trends Biochem Sci. 2004;29(2):72-79.
45. Rius J, Guma M, Schachtrup C, et al. NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α . Nature. 2008;453:807-811.
46. Shin T, Kuboki S, Lentsch AB. Roles of nuclear factor-κB in postischemic liver. Hepatol Res. 2008;38:429-440.
47. Gloire G, Legrand-Poels S, Piette J. NF-κB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol. 2006;72:1493-1505.
48. Balakumar P, Rohilla A, Sing M. Pre-conditioning and postconditioning to limit ischemia-reperfusion-induced myocardial injury: what could be the next footstep? Pharmacol Res. 2008;57:403-412.
49. Storz P, Döppler H, Toker A. Protein kinase Cδ selectively regulates protein kinase D-dependent activation of NF-κB in oxidative stress signalling. Mol Cell Biol. 2004;24(7):2614-2626.
50. Frangogiannis NG. Chemokines in ischemia and reperfusion. Thromb Haemos. 2007;97:738-747.
51. Teoh LKK, Grant R, Hulf JA, et al. The effect of preconditioning (ischemic and pharmacological) on myocardial necrosis following coronary artery bypass graft surgery. Cardiovasc Res. 2002;53:175-180.
52. Kutuk O, Basaga H. Aspirin inhibits TNFα-and IL-1-induced NF-κB activation and sensitizes HeLa cells to apoptosis. Cytokine. 2004;25:229-237.
53. Dirksen MT, Laarman GJ, Simoons ML, et al. Reperfusion injury in humans: a review of clinical trials on reperfusion injury inhibitory strategies. Cardiovasc Res. 2007;74:343-355.
54. Galagudza MM, Blokhin IO, Shmonin AA, et al. Reduction of myocardial ischemia-reperfusion injury with pre-and postconditioning: molecular mechanisms and therapeutic targets. Cardiovasc Haematol Disord Drug Targets. 2008;8:47-65.
55. Lindhardt TB, Gadsbøll N, Kelbæk H, et al. Pharmacological modulation of the ATP sensitive potassium channels during repeated coronary occlusions: no effect on myocardial ischaemia or function. Heart. 2004;90:425-430.
56. Leesar MA, Stoddard MF, Xuan YT, et al. Nonelectrocardiographic evidence that both ischemic preconditioning and adenosine preconditioning exist in humans. J Am Coll Cardiol. 2003;42(3):437-445.
57. Franco-Gou R, Roselĺo-Catafau J, Casillas-RamirezA, et al.How ischaemic preconditioning protects small liver grafts. J Pathol. 2006;208:62-73.
58. Ferencz A, Racz B, Gasz B, et al. Intestinal ischemic preconditioning in rats and NF-κB activation. Microsurgery. 2006;26(1):54-57. (Pubitemid 43244654)
59. Li XC, Ma YF, Wang XH. Role of NF-κB as effector of IPC in donor livers before liver transplantation in rats. Transplant Proc. 2006;38:1584-1587.
60. Morgan EN, Boyle EM, Wang Y, et al. An essential role for NF-κB in the cardioadaptive response to ischemia. Ann Thorac Surg. 1999;68:377-382.
61. Funaki H, Shimizu K, Harada S, et al. Essential role for nuclear factor αB in ischemic preconditioning for ischemia reperfusion injury of the mouse liver. Transplant. 2002;74(4):551-556.
62. Jiang SH, Liu CF, Zhang XL, et al. Renal protection by delayed\ischaemic preconditioning is associated with inhibition of the inflammatory response and NF-κB activation. Cell Biochem Funct. 2007;25:335-343.
63. Petrowsky H, McCormack L, Trujillo M, et al. A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection. Ann Surg. 2006;244(6):921-930.
64. Clavien PA, Yadav S, Sindram D, et al. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans. Ann Surg. 2000;232(2):155-162.
65. Clavien PA, Selzner M, Rüdiger HA, et al. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann Surg. 2003;238(6):843-852.
66. Cheung MMH, Kharbanda RK, Konstantinov IE, et al. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery. J Am Coll Cardiol. 2006;47(11):2277-2282.
67. Laskey WK, Beach D. Frequency and clinical significance of ischemic preconditioning during percutaneous coronary intervention. J Am Coll Cardiol. 2003;42(6):998-1003.
68. Hausenloy DJ, Mwamure PK, Venugopal V, et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 2007;370:575-579.
69. Bingyang JI, Liu M, Liu J, et al. Evaluation by cardiac troponin I: the effect of ischemic preconditioning as an adjunct to intermittent blood cardioplegia on coronary artery bypass grafting. Cardiac Surg. 2007;22:394-400.
70. Ali ZA, Callaghan CJ, Lim E, et al. Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair. Circulation. 2008;116(S1):I98-I105.
71. Konstantinov IE, Li J, Cheung MM, et al. Remote ischemic preconditioning of the recipient reduces myocardial ischemiareperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism. Transplantation. 2005;79:1691-1695.
72. Kharbanda RK,Mortensen UM, White PA, et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2002;106:281-2883.
73. Pasupathy S, Homer-Vanniasinkam S. Surgical implications of ischemic preconditioning. Arch Surg. 2005;140:405-409.
74. Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008;79(3):377-386.
75. Amador A, Grande L, Mart́i J, et al. Ischemic pre-conditioning in deceased donor liver transplantation: a prospective randomized clinical trial. Am J Transplant. 2007;7:2180-2189. (Pubitemid 47247061)
76. Ambros JT, Herrero-Fresneda I, Borau OG, et al. Ischemic preconditioning in solid organ transplantation: from experimental to clinics. Transpl Int. 2007;20:219-229.
77. Ji B, Liu M, Liu J, et al. Evaluation by cardiac troponin I: the effect of ischemic preconditioning as an adjunct to intermittent blood cardioplegia on coronary artery bypass grafting. J Cardiac Surg. 2007;22:394-400.
78. Gutíerrez SH, Kuri MR, Rojas del Castillo E. Cardiac role of the transcription factor NF-κB. Cardiovasc Haematol Disord Drug Targets. 2008;8:153-160.
79. Cha J,Wang Z,Ao L, et al. Cytokines link toll-like receptor 4 signaling to cardiac dysfunction after global myocardial ischemia. Ann Thorac Surg. 2008;85:1678-1685.
80. Boyd JH,Mathur S,Wang Y, et al. Toll-like receptor stimulation in cardiomyocytes decreases contractility and initiates an NF-κB dependent inflammatory response. Cardiovasc Res. 2006;72:384-393.
81. Shimamoto A, Chong AJ, Yada M, et al. Inhibition of tolllike receptor 4 with eritoran attenuates myocardial ischemiareperfusion injury. Circulation. 2006;114s:I270-I274.
82. Mullarkey M, Rose JR, Bristol J, et al. Inhibition of endotoxin response by E5564, a novel toll-like receptor 4-directed endotoxin antagonist. J Pharmacol Exp Ther. 2003;304(3):1093-1102.
83. Li C, Ha T, Kelley J, et al. Modulating toll-like receptormediated signalling by (1?3)-?-D-glucan rapidly induces cardioprotection. Cardiovasc Res. 2004;61:538-547.
84. Schulz R, Aker S, Belosjorow S, et al. TNFα in ischemia/ reperfusion injury and heart failure. Basic Res Cardiol. 2004;99:8-11.
85. Gu Q, Yang XP, Bonde P, et al. Inhibition of TNF-α reduces myocardial injury and proinflammatory pathways following ischemia-reperfusion in the dog. J Cardiovasc Pharmacol. 2006;48(6):320-328.
86. Yu X, Patterson E, Huang S, et al. Tumor necrosis factor α, rapid ventricular tachyarrhythmias, and infarct size in canine models of myocardial infarction. J Cardiovasc Pharmacol. 2005;45(2):153-159.
87. Esposito E, Mazzon E, Muìa C, et al. Splanchnic ischemia and reperfusion injury is reduced by genetic or pharmacological inhibition of TNF-α. J Leukoc Biol. 2007;81:1032-1043.
88. RusaiK,Huang H, SayedN, et al. Administration of interleukin-1 receptor antagonist ameliorates renal ischemia-reperfusion injury. Transpl Int. 2008;21:572-580.
89. Akuzawa S, Kazui T, Shi E, et al. Interleukin-1 receptor antagonist attenuates the severity of spinal cord ischemic injury in rabbits. J Vascular Surg. 2008;48(3):694-700.
90. Onai Y, Suzuki J, Kakuta T, et al. Inhibition of IκB phosphorylation in cardiomyocytes attenuates myocardial ischemia/ reperfusion injury. J Cardiovasc Res. 2004;63:51-59.
91. Moss NC, Stansfield WE, Willis MS, et al. IKKβ inhibition attenuates myocardial injury and dysfunction following acute ischemia-reperfusion injury. Am J Physiol. Heart Circ Physiol. 2007;293:2248-2253.
92. Oka S, Kamata H, Kamata K, et al. N-Acetylcysteine suppresses TNF-induced NF-κB activation through inhibition of IκB kinases. FEB S. 2000;472:196-202.
93. Tian XF, Zhang XS, Li YH, et al. Proteasome inhibition attenuates lung injury induced by intestinal ischemia reperfusion in rats. Life Sci. 2006;79:2069-2076.
94. Itoh M, Takaoka M, Shibata A, et al. Preventive effect of lactacystin, a selective proteasome inhibitor, on ischemic acute renal failure in rats. J Pharmacol Exp Therapeut. 2001;298(2):501-507.
95. Tian XF, Zhang XS, Li YH, et al. Proteasome inhibition attenuates lung injury induced by intestinal ischemia reperfusion in rats. Life Sci. 2006;79:2069-2076.
96. Yao JH, Li YH,Wang ZZ, et al. Proteasome inhibitor lactacystin ablates liver injury induced by intestinal ischaemia-reperfusion. Clin Exp Pharmacol Physiol. 2007;34:1102-1108.
97. Phillips JB, Williams AJ, Adams J, et al. Proteasome inhibitor PS519 reduces infarction and attenuates leukocyte infiltration in a rat model of focal cerebral ischemia. Stroke. 2000;31:1686-1693.
98. Zhang L, Zhang ZG, Zhang RL, et al. Postischemic (6-hr) treatment with recombinant human tissue plasminogen activator and proteasome inhibitor PS-519 reduces infarction in a rat model of embolic focal cerebral ischemia. Stroke. 2001;32:2926-2931.
99. Williams AJ, Berti R, Dave JR, et al. Delayed treatment of ischemia/ reperfusion brain injury: extended therapeutic window with the proteosome inhibitor MLN519. Stroke. 2004;35:1186-1191.
100. Ishiyama T, Dharmarajan S, Hayama M, et al. Inhibition of nuclear factor αB by IκB suppressor gene transfer ameliorates ischemia-reperfusion injury after experimental lung transplantation. J Thorac Cardiovasc Surg. 2005;130:194-201.
101. Kanaan SA, Kozower BD, Suda T, et al. Intratracheal adenovirus-mediated gene transfer is optimal in experimental lung transplantation. J Thorac Cardiovasc Surg. 2002;124:1130-1136.
102. Tagawa T, Kozower BD, Kanaan SA, et al. Tumor necrosis factor inhibitor gene transfer ameliorates lung graft ischemiareperfusion injury. J Thorac Cardiovasc Surg. 2003;126:1147-1154.
103. Suzuki T, Yamashita K, Jomen W, et al. The novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin, prevents local and remote organ injury following intestinal ischemia/reperfusion in rats. J Surg Res. 2008;149(1):69-75.
104. Ariga A, Namekawa JI, Matsumoto N, et al. Inhibition of tumor necrosis factor-induced nuclear translocation and activation of NF-κB by dehydroxymethylepoxyquinomicin. J Biol Chem. 2002;277(27):24625-24630.
105. Morishita R, Sugimoto T, Aoki M, et al. In vivo transfection of cis element "decoy" against nuclear factor-κB binding site prevents myocardial infarction. Nat Med. 1997;3(8):894-899.
106. Isner JM. Oligonucleotide therapeutics-novel cardiovascular targets. Nat Med. 1997;3(8):834-835.
107. Xu MQ, Shuai XR, Yan ML, et al. Nuclear factor-κB decoy oligodeoxynucleotides attenuates ischemia/reperfusion injury in rat liver graft. World J Gastroenterol. 2005;11(44):6960-6967.
108. Cao CC, Ding XQ, Ou ZL, et al. In vivo transfection of NF-κB decoy oligodeoxynucleotides attenuates renal ischemia/ reperfusion injury in rats. Kidney Int. 2004;65:834-845.
109. Banafsche R, Günther L, Nefflen JU, et al. NF-κB antisense oligonucleotides reduce leukocyte-endothelial interaction in hepatic ischemia-reperfusion. Transplant Proc. 2001;33:3726-3727.
110. Wang Y, Rangan GK, Tay YC, et al. Induction of monocyte chemoattractant protein-1 by albumin is mediated by nuclear factor αB in proximal tubule cells. J Am Soc Nephrol. 1999;10:1204-1213.
111. Qian JM, Zhang H, Wu XF, et al. Improvement of recipient survival after small size graft liver transplantation in rats with preischemic manipulation or administering antisense against nuclear factor-κB. Transpl Int. 2007;20:784-789.
112. Koopman PAR. Confidence intervals for the ratio of two binomial proportions. Biometrics. 1984;40:513-517.
113. Motulsky H. Intuitive Biostatistics, 1st ed. USA: Oxford University Press; 1995.
114. Price RM, Bonett DG. Distribution-free confidence intervals for difference and ratio of medians. J Stat Comput Sim. 2002;72(2):119-124.