Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/13160
標題: 利用高效能液相層析結合奈米銅網版印刷電極分析尿石患者尿中有機酸譜之研究
Profiling of Urolithic Organic Acids by Liquid Chromatography using Copper Nanoparticle Plated Electrodes
作者: 楊竣惟
Yang, Chun-Wei
關鍵字: urine;尿液;creatinine;organic acids;urolith;nanoparticle-plated electrode;肌酸酐;有機酸;尿石;奈米顆粒電極
出版社: 獸醫學系暨研究所
引用: 1. 李瀛輝、陳明村、張心湜:尿路結石之流行病學。尿路結石。第一版。臺北:九州圖書文物有限公司。1-17,1991。 2. 李瀛輝、張心湜、陳明村、黃榮慶:台灣南部地區尿路結石流行病學之研究。中華泌尿醫誌 5: 1 - 7,1994。 3. 林芳樹、王旭翔、馬永漢、陳淳:宜蘭縣內尿路結石症之臨床統計分析。台灣醫誌 93: 142 - 147,1994。 4. Antonia G, Mercedes M. Measurement of nephrolithiasis urinary markers by capillary electrophoresis. J Chramatog B 755: 287 – 295, 2001. 5. Bakker E. Electrochemical Sensors. Anal Chem 76: 3285 – 3298, 2004. 6. Bartages JW, Kirk C, Lane IF. Update: management of calcium oxalate uroliths in dogs and cats. Vet Clin North Am Small Anim Pract 34: 969 – 987, 2004. 7. Bartages JW, Osborne CA, Lulich JP, Kirk C, Allen TA, Brown C. Methods for evaluating treatment of uroliths. Vet Clin North Am Small Anim Pract 29: 45 – 58, 1999. 8. Bartages JW, Osborne CA, Lulich JP, Kruger JM, Ulrich LK. Canine urate urolithiasis: etiopathogenesis, diagnosis, and management. Vet Clin North Am Small Anim Pract 29: 161 – 192, 1999. 9. Barbas C, Garcia A, Saavedra L, Muros M. Urinary analysis of nephrolithiasis markers. J of chrematogra 781: 433 – 455, 2002. 10. Beshensky AM, Wesson JA, Worscster EM, Sorokina EJ, Snyder CJ, Kleinman JG. Effects of urinary macromolecules on hydroxyapatite crystal formation. J Am Soc Nephrol 12: 2108 – 2116, 2001. 11. Borghi L, Schianchi T, Meschi T, Guerra A, Allegri F, Maggiore U, Novarini A. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med 346: 77 – 84, 2002 12. Coe FL, Kavalach AG. Hypercalciuria and hyperuricosuria in patients with calcium nephrolithiasis. N Engl J Med 291:1344 – 1350, 1974. 13. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med 328: 833 – 838, 1993. 14. Chalermpol L, Osborne CA. Association between dietary factors and calcium oxalate and magnesium ammonium phosphate urolithiasis in cats. J Am Vet Med Assoc 219: 1229 - 1237, 2001. 15. Charles Y, Pak C. Predictive of kidney stone composition in the detection of metabolic abnormalities. Am J Med 115:26-32, 2003. 16. Cheng TH, Hueith JL. Profiling clinically important metabolites in human urine by an electrochemical system containing disposable electrodes. Sens Actuators B Chem 26: 132 – 187, 2005. 17. Chow K, Dixon J, Gilpin S, Kavanagh JP, Rao PN. Citrate inhibits growth of residual fragments in an in vitro model of calcium oxalate renal stone. Kidney Int 65: 1724 – 1730, 2004. 18. Corre KSL, Valsami E, Hobbs P, Parsons SA. Impact of calcium on struvite crystal size and purity. J Crystal growth 283: 514 – 522, 2005. 19. Daniel A, Feeney, Ralph C. Imaging Canine Urocystoliths: Detection and Prediction of Mineral Content. Vet Clin North Am Small Anim Pract 29: 59 – 72, 1999. 20. Daudon M, Donsimoni R, Hennequin C. Sex and age related composition of 10,617 calculi analyzed by infrared spectroscopy. Urol Res 23: 319 - 326, 1995. 21. Daudon M, Hennequin C, Boujelben G, Lacour B. Serial crystalluria determination and risk of recurrence in calcium stone formers. Kidney Int 67: 1934 – 1943, 2005. 22. Doreen M, Houston A. Feline urethral plug and bladder uroliths: a review of 5484 submissions 1998-2003. Can Vet J 44: 974 – 977, 2003. 23. Drach GW, Boyce WH. Nephrocalcinosis as a source for renal stone nuclei. observations on humans and squirrel monkeys and on hyperparathyroidism in the squirrel monkey. J Urol 107: 897 – 904, 1972. 24. Erent H, Knoll M. Electrochemical characterization of uric acid and ascorbic acid at a platinum electrode. Analytica chimica acta 449: 129 – 134, 2001. 25. Felix G, Antonia CB. Simple classification of renal calculi closely related to their micromorphology and etiology. Clinica Chimica Acta 322: 29 – 36, 2002. 26. Feeney DA, Weichselbaum RC, Jessen CR, Osborne CA. Imaging canine urocystoliths: detection and prediction of mineral content. Vet Clin North Am Small Anim Pract 29: 59 – 72, 1999. 27. Flocks RH. Calcium and phosphorus excretion in the urine of patients with renal or ureteric calculi. J Am Med Assoc 113: 1466 – 1489, 1939. 28. Garcia A, Muros M, Barbas C. Measurement of nephrosis urinary markers by capillary electrophoresis. J chromatography B 755: 287 – 295, 2001. 29. Grases F, Bauza L. Biopathological crystallization: a general view about the mechanism of renal stone formation. Adv Colloid Interface Sci 74: 169 – 194, 1998. 30. Grases F, Bauza AC, Ramis M, Montesinos V, Conte A. Simple classification of renal calculi closely related to their micromorphology and etiology. Clinica Chimica Acta 322: 29 – 36, 2002. 31. Grases F, Llobera A. Experimental model to study sedimentary kidney stones. Pergamon 29: 105 – 111, 1998. 32. Grases F, Villacampa AI, Bauza AC, Sohnel O. Uric acid calculi: types, etiology and mechanisms of formation. Clinica Chimica Acta 302: 89 – 104, 2000. 33. Hesse A, Brandle E, Wilbert D, Kohrmann KU, Alken P. Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs 2000. European Urology 44: 709 – 713, 2003. 34. Houston DM, Moore AEP, Favrin MG, Hoff B. Feline urethral plugs and bladder uroiths: a review of 5484 submissions 1998 – 2003. Can Vet J 44: 974 – 977, 2003. 35. Hsu CT, Lyuu HJ, Conte ED, YangTH , JM Zen. Profiling clinically important metabolites in human urine by an electrochemical system containing disposable electrodes. 36. Ito H, Coe FL: Acidic peptide and polyribonucleotide crystal growth inhibitors in human urine. Am J Physiol 233: 455 – 463, 1977. 37. Jen JF, Hsiao SL, Liu KH. Simultaneous determination of uric acid and creatinine in urine by eco-friendly solvent- free high performance liquid chromatographic method. Talanta 58: 711 – 717, 2002. 38. Koul HK, Koul S. Oxalate: from crystal formation to crystal retention. J Am Soc Nephrol 14: 417 – 421, 1999. 39. Kreder KJ, Willams RD: Urologic laboratory examination. In: Tanagbo EA, McAninch JW. Smith''s General Urology, 15th ed., New York: McGraw-Hill, 54 – 79, 2000. 40. Krieger JN, Kronmal RA. Dietary and behavior risk factors for urolithiasis: potential implications for prevention. Am J Kidney Dis 28: 195 - 201, 1996. 41. Kruger JM, Osborne CA, Lulich JP. Canine calcium phosphate uroliths: etiopathogenesis, diadnosis, and management. Vet Clin North Am Small Anim Pract 29: 141 - 161, 1999. 42. Krzysztof S, Zygmunt M. Analysis of purines in urinary calculi by high performance liquid chromatography. Analyt Biochem 286: 224 - 230, 2000. 43. Laube N, Michael M, Hergarten S, Schmidt M, Hesse A. The alteration of urine composition due to stone material present in the urinary tract. Europen Urology 44: 595 – 599, 2003. 44. Lee YH, Huang WC, Tsai JY, Lu CM, Chen WC, Lee MH, Hsu HS, Huang JK, Chang LS. Epidemiological Studies on the Prevalence of Upper Urinary Calculi in Taiwan. Urologia 68 172-177, 2002. 45. Lekcharoensuk C, Osborne CA, Lulich JP, Pusoonthornthum R. Association between dietary factors and calcium oxalate and magnesium ammonium phosphate urolithiais in cats. JAVMA 219: 1228 -1236, 2001. 46. Lulich JP, Osborne CA, Lekcharoensuk C, Allen TA, Nakagawa Y. Canine calcium oxalate urolithiasis: case-based applications of therapeutic principles. Vet Clin North Am Small Anim Pract 29: 123-140, 1999. 47. Lulich JP, Osborne CA, Sanderson SL, Ulrich LK, Swanson LL. Voiding urohydropropulsion: lessons from 5 years of experience. Vet Clin North Am Small Anim Pract 29: 283 - 292, 1999. 48. Lulich JP, Osborne CA, Thumchai R, Nakagawa Y. Epidemiology of Canine calcium oxalate uroliths: Identifying Risk Factors. Vet Clin North Am Small Anim Pract 29: 113-122, 1999. 49. Mathoera RB, Kok DJ, Nijman JM. Bladder calculi in augmentation cystoplasty in children. Urology 56: 482 - 487, 2000. 50. Menon M, Parulkar BG, Drach GW. Urinary lithiasis. In: Walsh WC, Retik AB, Vaughan ED, Wein AJ. Etiology. diagnosis and medical management. Campbell''s Urology. 7th ed, Philadelphia: W. B. Saunders Company, 2661-2733, 1998. 51. Menon M, Koul H: Clinical review 32: Calcium oxalate nephrolithiasis. J Clin Endocrinol Metab 74: 703 - 707, 1992. 52. Moran ME, Abrahams HM, Burday DE, Greene TD. Utility of oral dissolution therapy in the management of referred patients with secondarily treated uric acid stones. Urology 59: 206 – 210, 2002. 53. Neil W, Gill MC Gout and other crystal – associated arthropathies. Baillieres Clin Rheumatol 14: 445 – 460, 2000. 54. Ogawa Y, Yonou H, Hokama S. Urinary saturation and risk factors for calcium oxalate stone disease based in spot and 24-hour urine specimens. Front Biosci 8: 167 - 176, 2003. 55. Osborne CA, Jacob F, Lulich JP, Hansen MJ, Swanson LL. Canine silica urolithiasis: risk factors, detection, treatment, and prevention. Vet Clin North Am Small Anim Pract 29: 213 – 230, 1999. 56. Osborne CA, Lulich JP. Risk and protective factors for urolithiasis: what do they mean? Vet Clin North Am Small Anim Pract 29: 39 – 44, 1999. 57. Osborne CA, Lulich JP, Polzin DJ, Sanderson SL, Koehler LA, Ulrich LK, Sudo SZ. Analysis of 77,000 canine uroliths: perspectives from the Minnesota urolith center. Vet Clin North Am Small Anim Pract 29: 17 – 38, 1999. 58. Osborne CA, Lulich JP, Polzin DJ. Canine retrograde urohydropropulsion: lessons from 25 years of experience. Vet Clin North Am Small Anim Pract 29: 267 – 282, 1999. 59. Osborne CA, Lulich JP, Polzin DJ, Swanson LL. Medical dissolution and prevention of canine struvite urolithiasis: twenty years of experience. Vet Clin North Am Small Anim Pract 29: 73 – 112, 1999. 60. Osborne CA, Lulich JP, Bartges JW, Ulrich LK, Steinam KU. Drug induced urolithiasis. Vet Clin North Am Small Anim Pract 29: 251 – 266, 1999. 61. Osborne CA, Morris ML, Wheeler RC. Medical dissolution and prevention of canine uroliths: seven steps from science to service. Vet Clin North Am Small Anim Pract 29: 1 – 16, 1999. 62. Osborne CA, Sanderson SL, Lulich JP, Bartges JW, Swanson LL. Canine cystine urolithiasis : cause, detection, treatment, and prevention. Vet Clin North Am Small Anim Pract 29: 193 – 212, 1999. 63. Pak CYC, Peterson RD, Koska J, Sakhaee K. Citrate and renal calculi. Mineral & Electrolyte Metabolism Urology 60: 789 – 794, 2002. 64. Pak CYC, Poindexter JR, Huet BA, Pearle MS. Predictive value of kidney stone composition in the detection of metabolic abnormalities. Am J Med 115: 26 – 32, 2003. 65. Pak CYC. Kidney stones. Lancet 351:1797-1801, 1998. 66. Pak CYC, Resnick MI. Medical therapy and new approaches to management of urolithiasis. Urol Clin North Am 27: 243-253, 2000. 67. Pak CYC. Medical Management of Urinary Stone Disease. Nephron Clinical Practice 98: 49 - 53, 2004 68. Pak CYC. Medical Prevention of Renal Stone Disease. Nephron Clinical Practice 81: 60 - 65, 1999. 69. Pareek G, Armenakas NA, Panagopoulos G, Bruno JJ, Fracchia JA. Extracorporeal shock wave lithotripsy success based on body mass index and houns field units. Urology 65: 33-36, 2005. 70. Pizzato AC, Barros EJG. Dietary calcium intake among patients with urinary calculi. Nutr Res 23: 1651 – 1660, 2003. 71. Peres LAB, Molina AS, Galles MHL. Metabolic investigation of patients with urolithiasis in a specific region. Int Braz J Urol 29: 217 – 220, 2003. 72. Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. J AM Diet Assoc 95: 791 – 797, 1995. 73. Robertson WG, Peacock M, Marshall RW, Marshall DH, Nordin BE : Saturation-inhibition index as a measure of the risk of calcium oxalate stone formation in the urinary tract. N Engl J Med 29: 249 - 252, 1976. 74. Robertson WG, Jones JS, Heaton MA, Stevenson AE, Markwell PJ. Predicting the crystallization potential of urine from cats and dogs with respect to calcium oxalate and magnesium ammonium phosphate. J Nutr 132: 1637 – 1641, 2002. 75. Robert WG. A risk factor model of stone-formation. Front Biosci 8: 130 - 1138, 2003. 76. Ross SJ, Osborne CA, Lulich JP, Polzin DJ, Swanson LL. Canine and feline nephrolithiasis: epidemiology, detection, and management. Vet Clin North Am Small Anim Pract 29: 231 – 250, 1999. 77. Rutchik SD, Spirnak JP, Resnick MI, Ramchandani P: Introduction to upper tract stone disease. In: Pollack HM, McClennan BL, Dyer R, Kenney PJ, eds., Clinical Urolography, 2nd ed, Philadelphia: W. B. Saunders Company, 2138 - 2147, 2000 78. Ryrne KM, Bynum K. Calcium oxalate stone in feline littermates. J Feline Med 2: 111 - 114, 2000. 79. Sanjad SA, Abbad AA, Sabban EA. Primary hyperoxaluria type I : an underestimate cause of nephrocalcinosis and chronic renal failure in Saudi Arabian children. Ann Saudi Med 19: 4 – 7, 1999. 80. Schwartz BF, Schenkman N, Nguyen R, Stoller ML. Gahat: a napalese cure for urolithiasis? Urology 56: 912 – 914, 2000. 81. Shmohigoshi M, Karube I. Development of uric acid and oxalic acid sensors using a biothemochip. Sensors and actuators 30: 17 – 21, 1996. 82. Smith MJ, Hunt LD, King JS Jr, Boyce WH. Uricemia and urolithiasis. J Urol 101:637 – 642, 1969. 83. Smith BHE, Stevenson AE, Markwell PJ. Urinary relative supersaturations of calcium oxalate and struvite in cats are influenced by diet. J Nutr 128: 2763 – 2764, 1998. 84. Soldatkin AP, Montoriol J, Sant W, Martelet. Creatinine sensitive biosensor based on ISFETs and creatinine deiminase immobilihed in BSA membrane. Talanta 58: 351 – 357, 2002. 85. Srinivasan S, Kalaiselvi P, Sakthivel R, Pragasam V, Muthu V, Varalakshmi. U ric acid: an abettor or protector in calcium oxalate urolithiasis? Biochemical study in stone formers. Clinica Chimica Acta 353: 45 – 51, 2005. 86. Sturgess CP, Hesford A. An investigation into the effects of storage on the diagnosis of crystalluria in cats. J Feline Med 3: 81-85, 2001. 87. Takashi Y, Paramjit S. Metabolic risk factors in patients with first-time and recurrent stone formations as determined by comprehensive metabolic evaluation. Urology 52: 750-755, 1998. 88. Tiselius HG, Ackermann D, Alken P, Buck C, Conort P, Gallucci. Guideline on urolithiasis. Eur Urol 40: 362 – 371, 2001. 89. Tiselius HG, Ackermann D, Hess B, Boeve E. Stone disease: diagnosis and medical management. Eur Urol 41: 1 – 11, 2002. 90. Tolley DA. Urolithiasis: update on stone management. EAU Update series 3: 1 – 2, 2005. 91. Tosukhowong P, Borvonpadungkitti S, Sriboonlue P. Urinary citrate excretion in patients with renal stone: roles of leucocyte ATP citrate lyase activity and potassium salts therapy. Clinica Chimica Acta 325: 71 – 78, 2002. 92. Vupputuri S, Soucie JM, Mcclellan W, Sandler DP. History of kidney stones as a possible risk factor for chronic kidney disease. Ann Epidemiol 14: 222 – 228, 2004. 93. Walton RC, Kavanagh JP, Heywood BR, Rao PN. The association of different urinary proteins with calcium oxalate hydromorphs. Evidence for non-specific interactions. Biochimica et Biophysica Acta 1723: 175 – 183, 2005. 94. Weichselbaum RC, Feeney DA, Jessen CR. An integrated epidemiologic and radiographic algorithm for canine urocystolith mineral type prediction. Vet Radiol Ultrasound 42: 311 – 319, 2001. 95. Whalley NA, Martins MC, Van Dyk RC, Meyers AM: Lithogenic risk factors in normal black volunteers, and black and white recurrent stone formers. BJU Int 84:243 – 248, 1999. 96. Whalley NA, Moraes MF, Shar TG, Pretorius SS, Meyers AM: Lithogenic risk factors in the urine of black and white subjects. BJU Int 82:785 – 790, 1998. 97. William GR, Julie SJ. Predicting the crystallization potential of urine from cats and dogs with respect to calcium oxalate and magnesium ammonium phosphate. J Nutr 132: 1637 – 1641, 2002. 98. Yagisawa T, Chandhoke PS, Fan J. Metabolic risk factors in patients with first time and recurrent stone formation as determined by comprehensive metabolic evaluation. Urology 52: 750 – 755, 1998. 99. Yuji K, Satoshi Y. Changes in urinary parameters after oral administration of potassium-sodium citrate and magnesium oxide to prevent urolithiasis. Urology 63: 7 – 12, 2004. 100. Zen JM, Chen PY, Kumar AS. Flow injection analysis of an ultratrace amount of arsenite using a Prussian blue – modified screen – printed electrode. Anal Chem 75: 6017 – 6022, 2003. 101. Zen JM, Chung HH, Yang HH, Chiu MH, Sue JW. Photoelectrocatalytic oxidation of α- phenols on copper – plated screen – printed electrodes. Anal Chem 75: 7020 – 7025, 2003.
摘要: 
尿石症 (或尿結石) 泛指泌尿道內任一部位結石的存在及其對身體,尤其是泌尿系統造成之病症。目前尚無可靠方法有效預測結石之發生,但尿中形成結石之主要有機酸成份濃度過高被認為是結石形成之重要前置因子。因此,尿中有機酸成分之偵測對預防結石形成及復發極具價值。吾等發展出一高效能液相層析搭配電化學之偵測方法,可在13分鐘內成功分離胱氨酸、肌酸酐、尿酸、草酸和檸檬酸,其偵測極限約為nM等級,且標準品在移動相之RSD值在2.5% (肌酸酐) 至6.2% (胱胺酸) 之間,在尿液之RSD值在4.0% (草酸) 至7.7% (檸檬酸) 之間。
本實驗共收集包括人 (98例),犬 (86例) 及貓 (29例) 在內之213個正常及尿石患者的尿液樣品以及29個結石樣品進行有機酸含量分析。結果發現,人類尿石症患者尿中之草酸、尿酸及檸檬酸皆高於正常人尿液及結石中有機酸之含量,犬及貓之結果與人類並不完全相同。結果中並未發現任何單一參考值可用以預測結石之存在。然而,尿中各主要有機酸之比值極具推測尿石存在的參考價值。若結合各有機酸成份在尿中之濃度及其比值,將可有效區別正常及尿石尿液,代表此結果對推測及預測結石存在,極具潛力。檸檬酸可能扮演一個減少結石形成及影響尿中其他有機酸濃度之重要角色。人類尿石患者尿中離子濃度顯著較正常人尿中為低,但犬尿石尿中離子濃度卻與正常犬尿無顯著差異。研究中發現人與犬貓間之尿中有機酸譜及離子濃度種別差異非常明顯,顯示不同種別間尿石形成之條件及環境並不完全相同。總而言之,此開發之快速電化學層析方法應可有效應用於監控尿石症之可能形成及復發。

A simple and rapid high performance liquid chromatography method with electrochemical detection using disposable copper-nanoparticle-plated electrodes for simultaneous determination of major urolithic organic acids and creatinine is developed. Normal and urolithic human and canine urine samples were collected for direct analysis of creatinine, cystine, uric acid, oxalic acid, and citric acid without sample cleanup and derivatization process. Urinary organic acids were separated in 11 minutes with an anion exchange column using 0.1 M phosphate buffer at pH 7.5 as mobile phase. Optimal amperometric detection was achieved at low potentialwith detection limits in the nM levels and linear dynamic ranges spanning 2 to 3 orders of magnitude. The variations were between 2.5% and 6.2% in phosphate buffer and between 4.0% and 7.7% in urine, respectively. The recovery in urine ranged from 99.5% for creatinine to 86.6% for oxalic acid. Important differences in urolithic organic acid levels and profiles were unveiled among normal and urolithic urines and the urolith. The simplicity and reproducibility of this method has made a routine urine analysis possible and can be of great clinical and diagnostic importance to the study of urolithiasis and abnormal states related to excess secretion of organic acids in human and animals.
URI: http://hdl.handle.net/11455/13160
其他識別: U0005-0607200619394300
Appears in Collections:獸醫學系所

Show full item record
 

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.