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研究生:張士偉
研究生(外文):Chang Shih Wei
論文名稱:冠脂妥改善糖尿病大白鼠動靜脈廔管之血管內皮功能及提升廔管血流
論文名稱(外文):Rosuvastatin Potentiates Vascular Function And Restores Blood Flow In The Arteriovenous Fistula Of Rats With Streptozotocin-Induced Diabetes.
指導教授:郭玫君郭玫君引用關係林真福
指導教授(外文):Kuo Mei ChunLam Chen Fuh
口試委員:陳玟雅阮俊能
口試委員(外文):Chen Wen YaRoan Jun Neng
口試日期:2014-07-21
學位類別:碩士
校院名稱:嘉南藥理大學
系所名稱:生物科技系
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2014
畢業學年度:103
語文別:英文
論文頁數:51
中文關鍵詞:動靜脈瘻管內皮細胞糖尿病內皮前驅細胞冠脂妥
外文關鍵詞:Arteriovenous(AV) fistulaEndothelial cellDiabetes mellitusEndothelial progenitor cellRosuvastatin(Statin)
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糖尿病患者的動靜脈瘻管內血流有顯著的下降。據過去研究,史他汀這類的降血脂藥物有著多效性,除了降血脂外尚具有促進血管內皮細胞功能以及降低發炎反應的效果。本研究探討關於糖尿病患動靜脈瘻管喪失功能的病理機制,並試驗冠脂妥對糖尿病鼠動的靜脈瘻管是否具有保護的作用。
在大鼠身上注射單劑鏈佐黴素誘發糖尿病,並將大鼠隨機分為兩組,分別接受口服安慰劑以及冠脂妥(15mg/kg/d)。在誘發糖尿病後一週以手術方式在大鼠之降主動脈及下腔靜脈間製造一動靜脈瘻管。口服藥物治療期共為兩週(術前及術後各一週)。治療結束後測定瘻管之動脈端的血流流速、測試血管的等長收縮(Isometric force analysis),檢視週邊血液中內皮前驅細胞(CD34+/KDR+, endothelial progenitor cells)數目及分析瘻管組織中促發炎因子的表現以及超氧陰離子生成。
在糖尿病鼠血液中,血管內皮前驅細胞數量減少。而冠脂妥治療後可顯著地增加血管內皮前驅細胞的數量。在冠脂妥治療組的糖尿病大鼠,其動靜脈瘻管隻血流量、流速、血管內皮層舒張功能皆有明顯的改善作用。此外,冠脂妥亦可降低糖尿病鼠瘻管組織中iNOS以及NADPH oxidase的蛋白表現以及減少超氧陰離子和促發炎因子(TNF-α, IL-1β, IL-6)的生成。
本研究證實了冠脂妥可藉由抑制瘻管組織中促發炎基因之表現,以及降低超氧陰離子生成,達到改善糖尿病鼠之動靜脈瘻管的血流。本研究的發現提供臨床上改善糖尿病患者動靜脈瘻管失效之治療依據,並以口服冠脂妥作為改善糖尿病患者動靜脈瘻管功能及延長其使用壽命的有效治療方針。

Blood flow in the arteriovenous (AV) fistula is significantly reduced in diabetic patients. Statins are known to mediate pleiotropic effects in vascular endothelium and attenuate inflammatory responses. This study investigates the pathogenesis of AV fistula failure in subjects with diabetes mellitus, and tests the vascular protective effect of rosuvastatin on the fistulous communication of diabetic rats.
Diabetes mellitus (DM) was induced in rats by a single injection of streptozotocin. Rats were then randomly assigned to receive placebo or rosuvastatin (15 mg/kg/d) in chow for 2 weeks. One week induction of diabetes, a fistula was created in descending aorta and the adjacent IVC (AC fistula). Blood flow in the aortic and venous segments of fistula was measured. Circulating CD34+/KDR+ endothelial progenitor cells (EPCs) were determined using the flow cytometry. Vascular function of AC fistula was assessed by isometric force testing. The expression of pro-inflammatory genes and generation of superoxide anions in the fistula were examined.
Number of EPCs was reduced in diabetic rats, and rosuvastatin significantly increased numbers of circulating EPC. Reduced blood flow and impaired endothelium-dependent relaxation in the AC fistula of animals with diabetes was significantly potentiated following treatment with rosuvastatin. Rosuvastatin also attenuated the expression of iNOS and NADPH oxidase, generation of superoxide anions and proinflammatory cytokines (TNF-, IL-1 and IL-6) in the fistula tissues isolated from diabetic rats.
We provide the first evidence demonstrating that rosovastatin improves blood flow and endothelial function of AC fistula in rats with diabetes mellitus by attenuating the activity of pro-inflammatory genes and generation of superoxide anions in the remodeled vasculature. These experimental findings serve as fundamental supportive evidences for conducting clinical testing of the protective effect of HMG-CoA reductase inhibitor (statins) in establishing a durable vascular access for hemodialysis in diabetic patients.

Contents
Chinese Abstract...........................................................................................Ⅰ
English Abstract...........................................................................................Ⅲ
Contents...................................................................................................V
Figures of contents........................................................................................VII
Table of of contents.......................................................................................IX
List of abbreviations......................................................................................X
Chapter 1 Introduction.....................................................................................1
1.1 Hyperglycemia impairs vascular endothelia function and blood flow in AV fistula....................2
1.2 Sheer stress and regulation of eNOS plays an important role in vascular function and modulation of vascular structure..................................................................................................3
1.3 Hyperglycemia down-regulates eNOS expression and activity, and enhance inflammatory reactions......3
1.4 Independent to its lipid-lowering effect, HMG-CoA reductase inhibitors have pleiotrophic effects potentiating vascular function, especially the protective effects on endothelial function...............................4
1.5 HMG-CoA reductase inhibitors mobilize circulating endothelial progenitor cells, which mediate endogenous repair mechanism of endothelium...................................................................................5
1.6 Hypothesis and objectives..........................................................................7
Chapter 2 Material and Methods.............................................................................9
2.1 Animal Models and Experiments........................................................................9
2.2 Induction of hyperglycemia in rats...................................................................9
2.3 Treatment protocol..................................................................................10
2.4 Hemodynamic measurements............................................................................10
2.5 Vasomotor function assessment.......................................................................11
2.6 Measurement of circulating endothelial progenitor cells and blood chemistry.........................11
2.7 Determinations of superoxide anions, cGMP and proinflmmatory gene expressions.......................12
2.8 Assays for proinflammatory cytokines................................................................12
2.9 Histological sections...............................................................................12
Chapter 3 Results.........................................................................................13
3.1 Blood biochemistry analysis and number of circulating EPCs............................................13
3.2 Hemodynamic measurements..............................................................................13
3.3 Vasomotor function assessments........................................................................14
3.4 Generation of superoxide anions and expression of proinflammatory genes...............................14
3.5 Histological examination..............................................................................15
Chapter 4 Discussion .....................................................................................16
Chapter 5 Conclusion......................................................................................24
Reference.................................................................................................25
Appendix..................................................................................................37
Figure 1. Biosynthesis of cholesterol through the mevalonate pathway......................................37
Figure 2. Pleiotropic protective effect statins on the biological function of endothelial nitric oxide synthase (eNOS) in the endothelial cells.....................................................................................38
Figure 3. Rat model of aortocaval fistula.................................................................39
Figure 4. Mobilization of endothelial progenitor cells (EPCs) in wild-type (control) and diabetic rats....40
Figure 5. The cardiac performance was assessed by left ventricular ejection fraction (LVEF) during ventricular contraction-relaxation cycles at M-mode...............................................................................41
Figure 6. Measurement of blood flow in the arterial site of AV fistula....................................42
Figure 7. Measurement of luminal diameter (A) and fistula blood flow (B) using a transcutaneous scanning Duplex ultrasound transducer................................................................................................43
Figure 8. Measurements of isometric force of aorta isolated from the AV fistula of rats with or without diabetes mellitus..................................................................................................44
Figure 9. Generation of superoxide anions in the blood vessel tissues of AV fistula.......................45
Figure 10. Tissue concentrations of cGMP in the arterial site of AV.......................................46
Figure 11. Western blot analysis of the expressions of proinflammatory genes in the AV fistula............47
Figure 12. Tissue concentrations of proinflammatory cytokines in the venous tissue of AV fistula..........48
Figure 13. Representative histological sections of arterial tissue of AV fistula..........................49
Table 1. Serum levels of glucose and lipid profiles in control and diabetic rats..........................50
Table 2. Pressure gradients and flow velocity measured at arteriovenous fistula...........................51



References
1. Yang WC, Hwang SJ, Chiang SS, Chen HF, Tsai ST. The impact of diabetes on economic costs in dialysis patients: experiences in Taiwan. Diabetes Research and Clinical Practice. 2001; 54: S47-S54.
2. Joseph S, Adler S: Vascular access problems in dialysis patients: pathogenesis and strategies for management. Heart Dis. 2001; 3: 242-7.
3. Allon M, Robbin ML. Increasing arteriovenous fistulas in hemodialysis patients: problems and solutions. Kidney Int. 2002; 62: 1109-24.
4. Windus DW. Permanent vascular access: a nephrologist's view. Am J Kdney Dis. Am J of Kidney Dis 1993; 21: 457-71.
5. Pichler G, Urlesberger B, Jirak P, et al. Reduced forearm blood flow in children and adolescents with type 1 diabetes. Diabetes Care 2004; 27: 1942-6.
6. Tonelli M, Hirsch DJ, Chan CT, et al. Factors associated with access blood flow in native vessel arteriovenous fistulae. Nephro Dial Transplant 2004; 19:2559-63.
7. Fitzgerald JT, Schanzer A, Chin AI, McVicar JP, Perez RV, Troppmann C. Outcomes of upper arm arteriovenous fistulas for maintenance hemodialysis access. Arch of Surg 2004; 139: 201-8
8. Lehoux S, Tedgui A. Cellular mechanics and gene expression in blood vessels. J Biomech. 2003; 36: 631-43.
9. Boo YC, Jo H. Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinase. Am J Phyiol Cell Physiol 2003; 285: 499-508.
10. Garcia-Cardena G, Fan R, Shah V, Sorrentino R, et al. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 1998; 392: 821-4.
11. Ortiz PA, Hong NJ, Garvin JL. Luminal flow induces eNOS activation and translocation in the rat thick ascending limb. II. Role of PI3-kinase and Hsp90. Am J Physiol 2004; 287: 281-288.
12. Goligorsky MS, Li H, Brodsky S, Chen J: Relationships between caveolae and eNOS: everything in proximity and the proximity of everything. Am J Physiol 2002; 283: 1-10.
13. Katusic ZS: Vascular endothelial dysfunction: does tetrahydrobiopterin play a role? Am J Physiol 2001; 281: 981-986.
14. Kobayashi T, Kamata K. Effect of chronic insulin treatment on NO production and endothelium-dependent relaxation in aortae from established STZ-induced diabetic rats. Atherosclerosis 2001; 155: 313-21
15. Du XL, Edelstein D, Dimmelar S, Ju Q, Sui C, Brownlee M. Hyperglycemia inhibits endothelial nitric oxided synthase activity by posttranslational modification at the Akt site. J Clin Investig 2001; 108: 1341-8.
16. Alp NJ, Mussa S, Khoo J, et al. Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression. J Clin Investig 2003; 112: 725-35.
17. Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109 (23 suppl 1): III50-III57.
18. Calabro P, Yeh ETH. The pleiotropic effects of statins. Curr Opinion Cardiol 2005; 20: 541-6.
19. Laws PE, Spark JI, Cowled PA, Fitridge RA. The role of statins in vascular disease. Eur J Vasc Endovasc Surg 2004; 27: 6-16.
20. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study. Lancet 1994; 344: 1383-9.
21. The Long-Term Intervention with Pravastatin In Ischemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravostatin in patients with coronary heart diesase and a broad range of initial cholesterol levels. N Engl J Med. 1998; 339: 1349-57
22. Egashira K, Hirooka Y, Kai H, et al. Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 1994; 89: 2519-24.
23. Dupuies J, Tardif JC, Cernacek P, Theroux P: Cholesterol reduction rapidly improves endothelial function after coronary syndromes. Circulation 1999; 99: 3227-33.
24. Laufs U, La Fata V, Plutzky J, Liao JK: Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998; 97: 1129-35.
25. Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI3 kinase/Akt pathway. J Clin Invest 2001; 108: 391-7.
26. Werner N, Priller J, Laufs U, et al. Bone marrow-derived progenitor cells modulate vascular reendothelialzation and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition. Arterioscler Thromb Vasc Biol. 2002; 22: 1567-72.
27. Walter DH, Rittig K, Bahlmann FH, et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation. 2002; 105: 3017-24.
28. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275: 964-7.
29. Rafii S, Lyden D: Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med. 2003; 9: 702-12.
30. Asahara T, Kawamoto A: Endothelial progenitor cells for postnatal vasculogenesis. Am J Phyiol Cell Physiol. 2004; 287: 572-9.
31. Llevadot J, Murasawa S, Kureishi Y, et al. HMG-CoA reductase inhibitor mobilizes bone-marrow drived endothelial progenitor cells. J Clin Invest 2001; 108: 399-405.
32. Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999; 5: 434-8.
33. Urbich C, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med. 2003; 9: 1370-6.
34. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling an dimproves cardiac function. Nat Med. 2001; 7: 430-6.
35. Kawamoto A, Gwon HC, Iwaguro H, et al. Therapeutic Potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation. 2001; 103: 634-7.
36. He T, Smith L, Harrington S, Nath K, Caplice NM, Katusic ZS: Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke. 2004; 35: 2378-84.
37. Kaushal S, Amiel GE, Guleserian KJ, et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med. 2000; 7: 1035-40.
38. Assmus B, Schachlinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation. 2002; 106: 3009-17.
39. Perin EC, Dohmann HFR, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for sever, chronic ischemic heart failure. Circulation. 2003; 107: 2294-302.
40. Stamm C, Westphal B, Kleine HD, et al.Autologous bone marrow transplantation for myocardial regeneration. Lancet. 2003; 361: 45-6.
41. Lam CF, Liu YC, Hsu JK, et al. Autologous transplantation of endothelial progenitor cells attenuates acute lung injury in rabbits. Anesthesiology. 2008; 108: 392-401.
42. Burnham EL. Circulating progenitors in lung injury: a novel therapy for acute respiratory distress syndrome? Anesthesiology. 2008; 108: 354-6.
43. He T, Peterson TE, Holmuhamedov EL, et al. Human endothelial progenitor cells tolerate oxidative stress due to intrinsically high expression of manganese superoxide dismutase. Arterioscler Thromb Vasc Biol. 2004; 24: 2021-7.
44. Dernbach E, Urbich C, Brandes RP, Hofmann WK, Zeiher AM, Dimmeler S: Antioxidative stress-associated genes in circulating progenitor cells: evidence for enhanced resistance against oxidative stress. Blood. 2004; 104: 3591-7.
45. Nath KA, Kanakiriya SK, Grande JP, Croatt AJ, Katusic ZS: Increased venous proinflammatory gene expression and intimal hyperplasia in an aortocaval fistula model in the rat. Am J Pathol.2003; 162: 2079-90.
46. Kirk JE, Wilkins MR: Renal effects of concurrent E-24.11 and ACE inhibition in the aorto-venocaval fistula rat. Br J Pharmacol. 1996; 119: 943-8.
47. Roan JN, Yeh CY, Chiu WC, et al. Functional dilatation and medial remodeling of the renal artery in response to chronic increased blood flow. Kidney Blood Press Res. 2011; 34: 447-56.
48. Blanco-Rivero J, de las Heras N, Martin-Fernandez B, Cachofeiro V, Lahera V, Balfagon G. Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats. Br J Pharmacol. 2011; 162: 271-85.
49. Corsini A, Bellosta S, Baetta R, Fumagalli R, Paoletti R, Bernini F. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther. 1999; 84: 413-28.
50. Roan JN, Tsai YC, Chen IW, Chang SW, Huang CC, Lam CF: Inhibition of cyclooxygenase-2 modulates phenotypic switching of vascular smooth muscle cells during increased aortic blood flow. Heart Vessels 2012; 27(3):307-15.
51. Varaprasathan GA, Araoz PA, Higgins CB, Reddy GP.Quantification of flow dynamics in congenital heart disease: applications of velocity-encoded cine MR imaging. Radiographics .2002; 22: 895-905.
52. Lam CF, Liu YC, Tseng FL, et al. High-dose morphine impairs vascular endothelial function by increased production of superoxide anions. Anesthesiology. 2007; 106: 532-7.
53. Lam CF, Chang PJ, Huang YS, et al. Prolonged use of high-dose morphine impairs angiogenesis and mobilization of endothelial progenitor cells in mice. Anesth Analg. 2008; 107: 686-92.
54. Schinstock CA, Albright RC, Williams AW, et al. Outcomes of arteriovenous fistula creation after the fistula first initiative. Clin J Am Soc Nephrol. 2011; 6: 1996-2002.
55. Monroy-Cuadros M, Yilmaz S, Salazar-Banuelos A, Doig C: Independent prediction factors for primary patency loss in arteriovenous grafts within six months. J Vasc Access. 2012;13:29-35.
56. Dixon BS, Beck GJ, Vazquez MA, et al. Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med. 2009; 360: 2191-201.
57. Righetti M, Ferrario G, Serbelloni P, Milani S, Tommasi A: Some old drugs improve late primary patency rate of native arteriovenous fistulas in hemodialysis patients. Ann Vasc Surg. 2009; 23: 491-7.
58. Pisoni R, Barker-Finkel J, Allo M: Statin therapy is not associated with improved vascular access outcomes. Clin J Am Soc Nephrol. 2010; 5: 1447-50.
59. Juncos JP, Grande JP, Kang L, et al. MCP-1 contributes to arteriovenous fistula failure. Am J Soc Nephrol. 2011; 22: 43-8.
60. Caplice NM, Wang S, Tracz M, et al. Neoangiogenesis and the presence of progenitor cells in the venous limb of an arteriovenous fistula in the rat. Am J Physiol Renal Physiol. 2007; 293: 470-475.
61. Tesfamariam B, Cohen RA: Free radicals mediate endothelial cell dysfunction caused by elevated glucose. Am J Physiol. 1992; 263: 321-326.
62. Brandes RP, Kreuzer J: Vascular NADPH oxidases: molecular mechanisms of activation. Cardiovasc Res. 2005; 65: 16-27.
63. Szabo C: Role of nitrosative stress in the pathogenesis of diabetic vascular dysfunction. Br J Pharmacol. 2009; 156: 713-27.
64. Deshmane SL, Kremlev S, Amini S, Sawaya BE: Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res. 2009; 29: 313-26.
65. Yang J, Park Y, Zhang H, et al. Role of MCP-1 in tumor necrosis factor-alpha-induced endothelial dysfunction in type 2 diabetic mice. Am J Physiol Heart Circ Physiol. 2009; 297: 1208-16.
66. Alexandraki K, Piperi C, Kalofoutis C, Signh J, Alaveras A, Kalofoutis A. Inflammatory process in type 2 diabetes: The role of cytokines. Ann NY Acad Sci. 2006; 84: 89-117.
67. Sironi L, Gianazza E, Gelosa P, et al. Rosuvastatin, but not simvastatin, provides end-organ protection in stroke-prone rats by antiinflammatory effect. Arterioscler Thromb Vasc Biol. 2005; 25: 598-603.
68. Erdos B, Snipes JA, Tulbert CD, Katakam P, Miller AW, Busija DW: Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production. Am J Physiol Heart Circ Physiol. 2006; 290: 1264-70.
69. Kim YO, Yang CW, Yoon SA, et al. Access blood flow as a predictor of early failures of native arteriovenous fistulas in hemodialysis patients. Am J Nephrol. 2001; 21: 221-5.
70. Asif A, Roy-Chaudhury P, Beathard GA: Early arteriovenous fistula failure: a logical proposal for when and how to intervene. Clin J Am Soc Nephrol. 2006; 1: 332-9.
71. Roan JN, Fang SY, Chang SW, et al: Rosuvastatin improves vascular function of arteriovenous fistula in a diabetic rat model. J Vasc Surg. 2012; 56: 1381-9.
72. Bui TD, Gordon IL, Parashar A, Vo D, Wilson SE: Resistance within hemodialysis shunts predicts patency. Vasc Endovascular Surg. 2006; 40: 295-302.
73. Weiss MF, Scivittaro V, Anderson JM: Oxidative stress and increased expression of growth factors in lesions of failed hemodialysis access. Am J Kidney Dis. 2001; 37: 970-80.
74. Fadini GP, Miorin M, Facco M, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005; 45: 1449-57.
75. Krankel N, Adams V, Linke A, et al. Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells. Arterioscler Thromb Vasc Biol. 2005; 25: 698-703.
76. Jaumdally RJ, Goon PK, Varma C, Blann AD, Lip GY: Effects of atorvastatin on circulating CD34+/CD133+/ CD45- progenitor cells and indices of angiogenesis (vascular endothelial growth factor and the angiopoietins 1 and 2) in atherosclerotic vascular disease and diabetes mellitus. J Intern Med. 2010; 267: 385-93.
77. Reinhard H, Jacobsen PK, Lajer M, et al. Multifactorial treatment increases endothelial progenitor cells in patients with type 2 diabetes. Diabetologia. 2010; 53: 2129-33.
78. Povsic TJ, Goldschmidt-Clermont PJ: Endothelial progenitor cells: markers of vascular reparative capacity. Ther Adv Cardiovasc Dis. 2008; 2: 199-213.



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