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研究生:葉怡柔
研究生(外文):Yeh I-Rou
論文名稱:葛根之代謝動力學及其對環孢靈、地高辛動力學之影響
論文名稱(外文):Metabolic Pharmacokinetics of Puerariae Radix and Its Effects on the Pharmacokinetics of Cyclosporine and Digoxin
指導教授:李珮端李珮端引用關係徐素蘭徐素蘭引用關係
指導教授(外文):Chao P. D. L.Hsiu S. L.
學位類別:碩士
校院名稱:中國醫藥學院
系所名稱:中國藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
中文關鍵詞:葛根動力學高效液相層析交互作用環孢靈葛根素大豆大豆元
外文關鍵詞:Puerariae RadixPharmacokineticsHPLCdrug-drug interactioncyclosporinepuerarindaidzindaidzein
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摘 要
葛根 (Puerariae Radix) 含豐富異黃酮成分,包括葛根素(puerarin)、大豆(daidzin)、大豆元(daidzein)等,具有優越藥理活性。本研究探討人與大白鼠口服葛根水煎劑或濃縮散劑後之代謝動力學及葛根對環孢靈及地高辛動力學之影響。
利用高效液相層析法,以梯度沖提,同時分析葛根水煎劑及濃縮散劑中葛根素、大豆及大豆元之含量。分析九種飲片之水煎劑及八種濃縮散劑之結果顯示,葛根水煎劑中,每公克飲片含葛根素、大豆和大豆元,分別為4.0 ± 0.7、0.8 ± 0.1及0.2 ± 0.05 mg,每公克濃縮散劑中之含量則為9.8 ± 0.7、1.4 ± 0.1 及0.4 ± 0.03 mg。
大白鼠口服葛根濃縮散劑,以心臟穿刺採血,血藥濃度之定量,係以-glucuronidase及sulfatase 分別水解後,利用高效液相層析法定量daidzein。結果顯示, daidzein結合態代謝物中以sulfates為主,而glucuronides較少。
十位受試者口服相等異黃酮含量之水煎劑及濃縮散劑後,36小時內分段收集尿液,經 -glucuronidase及sulfatase 分別水解後,利用高效液相層析法定量daidzein,計算尿中daidzein glucuronides及sulfates之累積排出量及其佔口服劑量之百分比。結果顯示,口服濃縮散劑後尿中daidzein glucuronides及daidzein sulfates之排出量,比水煎劑顯著減少了58.1 % 及51.4 %。
近年來中西藥併服情況日益普遍,對於治療窗狹窄之環孢靈及地高辛尤其值得關注。本實驗以大白鼠為模型,探討葛根對環孢靈及地高辛動力學之影響。環孢靈與地高辛之血中濃度,係以螢光偏極免疫法定量。研究結果顯示,大白鼠併服葛根散劑時,對靜注之地高辛血藥面積影響不大。大白鼠併服葛根水煎劑時,血液中環孢靈之血藥面積及血峰濃度顯著降低了62.8 %及62.2 %,而併服濃縮散劑時,顯著降低了74.9 % 及80.3 %,葛根明顯降低環孢靈之口服生可用率。因此,為確保療效及用藥安全,應避免併服環孢靈與葛根。
YI-ROU YEH
Graduate Institute of Chinese Pharmaceutical Science, China Medical College, Taichung, Taiwan, ROC.
ABSTRACT
Puerarin, daidzin and daidzein are bioactive isoflavone constituents of Puerariae Radix. This study aimed to investigate the metabolic pharmacokinetics of these isoflavones after oral administrations of traditional decoction and commercial extract of Puerariae Radix in rats and humans and to measure the effects on the pharmacokinetics of cyclosporine and digoxin.
Nine crude drugs and eight brands of commercial extracts of Puerariae Radix were purchased from the market and their contents of puerarin, daidzin and daidzein were determined by gradient HPLC. The contents of puerarin, daidzin and daidzein in traditional decoctions of each gram Puerariae Radix were 4.0 ± 0.7 mg, 0.8 ± 0.1 mg and 0.2 ± 0.05 mg, whereas those in each gram commercial extracts were 9.8 ± 0.7 mg, 1.4 ± 0.1 mg and 0.4 ± 0.03 mg, respectively.
Rats were given commercial extract of Puerariae Radix. Blood samples were withdrawn via cardiopuncture and assayed by HPLC method after enzymatic hydrolysis withβ-glucuronidsae and sulfatase, respectively. Daidzein sulfates were found predominantly in the bloodstream, whereas daidzein glucuronides presented in less amount.
Ten healthy male volunteers ingested traditional decoction and commercial extract which contain equivalent amount of isoflavones in a crossover design. The absorption was measured by urinary recoveries of daidzein glucuronides and sulfates within 36 h. The concentration of daidzein in urine was determined by HPLC after enzymatic hydrolysis with β-glucuronidsae and sulfatase, respectively. The cumulated urinary recoveries (% of dose) of daidzein glucuronides and sulfates after dosing commercial extract were significantly lower than those after dosing traditional decoction by 58.1 % and 51.4 %, respectively.In recent years, there has been a growing attention paid to interactions between herbs and pharmaceuticals, especially drugs with narrow therapeutic index. This study investigated the effects of Puerariae Radix on the pharmacokinetics of cyclosporine and digoxin. The blood concentrations of cyclosporine and digoxin were determined by FPIA method. No significant effect on pharmacokinetics of digoxin was found. The AUC0-t and Cmax of cyclosporine were significantly decreased by 62.8 % and 62.2 %, respectively, after coadministration with traditional decoction of Puerariae Radix and by 74.9 % and 80.3 %, respectively, after coadministration with its commercial extract. We suggested that for the sake of efficacy, the coadministration of Puerariae Radix with cyclosporine should be avoided.
附圖目錄………………………………………………………III
附表目錄………………………………………………………VII
中文摘要………………………………………………………XII
英文摘要………………………………………………………XIV
第一章 緒言…………………………………………………1
第二章 總論…………………………………………………4
第一節 葛根之本草學考察………………………………4
第二節 葛根之化學成分…………………………………8
第三節 葛根素、大豆與大豆元之結構與理化性質12
第四節 葛根之藥理活性考察……………………………15
第五節 葛根之動力學考察………………………………20
第六節 環孢靈(Cyclosporine)之特性………………22
第七節 地高辛(Digoxin)之特性 ……………………24
第三章 實驗部份……………………………………………26
第一節 實驗材料…………………………………………26
一、實驗試藥………………………………………………26
二、儀器設備………………………………………………28
三、實驗動物………………………………………………29
四、溶液製備………………………………………………29
第二節 實驗方法…………………………………………32
一、 葛根水煎劑及濃縮散劑中puerarin、daidzin 與
daidzein之HPLC定量分析…………………………32
二、大白鼠口服葛根濃縮散劑之動力學…………………37
三、葛根水煎劑與濃縮散劑於人體吸收之比較…………43
四、葛根水煎劑與濃縮散劑於大白鼠體內對環孢靈動
力學之影響………………………………………………47
五、葛根濃縮散劑於大白鼠體內對地高辛動力學之影響…50
六、葛根水煎劑對P-glycoprotein功能之影響……………52
第四章 結果與討論……………………………………………54
一、 葛根水煎劑及濃縮散劑中puerarin、daidzin 與
daidzein 之HPLC定量分析……………………………54
二、大白鼠口服葛根濃縮散劑之動力學……………………57
三、葛根水煎劑與葛根濃縮散劑於人體吸收之比較 ………61
四、葛根水煎劑與濃縮散劑於大白鼠體內對環孢靈、地高辛
動力學之影響………………………………………………65
參考文獻…………………………………………………………113
附錄………………………………………………………………124
參考文獻
1. Xu X, Duncan AM, Merz BE, Kurzer MS. Effect of soy isoflavone on estrogen and phytoestrogen metabolism in premenopausal woman. Cancer Epidemiol Biomakers Prev. 1998;7:pp. 1101-8.
2. Adlercreutz H. Western diet and Western diseases:some hormonal and biochemical mechanisms and association. Scand J Clin Lab Invest Suppl. 1990 ; 201 : pp. 3-23.
3. Adlercreutz H, Honjo H, Higashi A, Fotsis T, Hamalainen E, Hasegawa T, Okada H. Urinary excretion of ligans and isoflavonoid phytoestrogen in Japanese men and women consuming a traditional Japanese diet. Am J Clin Nutr. 1991 ; 54 : pp. 1093-100.
4. Potter SM, Baum JA, Teng HY, Stillman RJ, Erdman JW. Soy protein and isoflavones : their effect on blood lipid and bone density in postmenopausal women. Am J Clin Nutr. 1998 ; 68 : pp. 1375S-9S.
5. Setchell KD, Cassidy A. Dietary isoflavones : biological effects and relevance to human heath. J Nutr. 1999;129:pp. 758-67.
6. Barnes S, Sfakianos J, Coward L, Kirk M. Soy isoflavonoids and cancer prevention : Underlying biochemical and pharmacological issues. Adv Exp Med Biol. 1996;401:pp. 87-100.
7. 中華本草,上海科學技術出版社,西安 1995;4 : pp. 610-9。
8. 中國醫學科學院藥物研究所,中草藥現代研究 第一卷,北京醫科 大學中國協和醫科大學聯合出版社,北京 1995;pp. 260-7。
9. 郭建平、孫其榮、周全:葛根藥理作用研究進展,中草藥,1995 ; 3:pp. 163-5。
10. Fan LL, Sun LH, Li J, Yue XH, Yu HX, Wang SY. The protective effects of puerarin against myocardial reperfusion injury study on cardiac function (J). Chin Med J. 1992;105 : pp. 11-7.
11. Yue HW, Hu XQ. Pharmacologic value of radix Puerariae and puerarine on cardiovascular system. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1996;16 : pp. 382-4.
12. 曾貴雲、周遠鵬:葛根的藥理研究,中華醫學雜誌,1974;54 : pp. 265-70。
13. Lu XR, Gao E, Xu LZ, Li HZ, Kang B, Chen WN, Chen SM, Chai XS. Puerarin beta-adrenergic receptor blocking effect. Chin Med J. 1987;100 : pp. 25-8.
14. 段重高、徐理納、李宏偉:葛根素對金黃鼠腦循環的影響,中華醫學雜誌,1991;71 : pp. 516-7。
15. 李桂明:葛根素注射液治療腦梗塞45例療效觀察,新中醫,1998;30:pp. 36-7。
16. 黃兆宏、金之瑾、何耕興:葛根素對牛動脈內皮的作用,老年學雜誌,1992;12 : pp. 350-1。
17. Yin ZZ, Zeng GY. Pharmacology of puerarin (V). Effects of puerarin on platelet aggregation and release of 5-HT from platelets. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1981;Suppl 1: pp. 44-7.
18. Shen ZF, Xie MZ. Hypoglycemic effect of the combined use of puerarin and aspirin in mice. Yao Xue Xue Bao. 1985 ; 20 : pp. 863-5.
19. van der Schouw YT, de Kleijn MJ, Peeters PH, Grobbee DE. Phyto oestrogens and cardiovascular disease risk. Nutr Metab Cardiovasc Dis. 2000 ; 10 : pp. 154-67.
20. 孫世錫:幾種中藥解熱作用之藥理研究,中華醫學雜誌,1956;42 : pp. 964-8。
21. 簿廷相:葛根的解痙作用,遼寧中醫雜志,1981;7:pp. 27。
22. 王紅、許哲、劉干中:葛根及川芎對動物學習記憶的影響,中日友好醫院學報,1995;9 : pp. 191-4。
23. Messina MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk : a review of the in vitro and in vivo data. Nutr Cancer. 1994 ; 21 : pp. 113-31.
24. Han R. Highlight on the studies of anticancer drugs derived from plants in China. Stem Cells. 1994 ; 12 : pp. 53-63.
25. Jing Y, Nakaya K, Han R. Differentiation of promyelocytic leukemia cells HL-60 induced by daidzein in vitro and in vivo. Anticancer Res. 1993 ; 13 : pp. 1049-54.
26. 杜德極、冉長青、石小楓:葛根對腫瘤壞死因子產生及巨噬細胞功能的影響,中藥藥理與臨床,1995;11:pp. 16-9。
27. Zhang R, Li Y, Wang W. Enhancement of immune function in mice fed high dose of soy daidzein. Mut and Cancer. 1997;29:pp. 24.
28. Arora A, Nair MG, Strasburg GM. Antioxidant activities of isoflavones and their biological metabolites in a liposomal system.
Arch Biochem Biophys. 1998 ; 356 : pp. 133-41.
29. Jha HC, von Recklinghuasen G, Zilliken f. Inhibition of in vitro microsomal lipid peroxidation by isoflavonoids. Biochem Pharmaco 1985;34:pp. 1367-9.
30. 霍美玲、項永生:葛根解救溴氰菊酯中毒的研究,山東醫藥,1987;27 : pp. 27.
31. Keung WM, Vallee BL. Kudzu root : an ancient Chinese source of modern antidipsotropic agents. Phytochemistry. 1998 ; 47 : pp. 499-506.
32. Keung WM, Vallee BL. Daidzin : a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase. Proc Natl Acad Sci. 1993;90 : pp. 1247-51.
33. Keung WM, Vallee BL. Daidzin and its antidipsotropic analogs inhibit serotonin and dopamine metabolism in isolated mitochondria. Proc Natl Acad Sci USA. 1998;95 : pp. 2198-203.
34. Keung WM. Biochemical studies of a new class of alcohol dehydrogenase inhibitors from Radix puerariae. Alcohol Clin Exp Res. 1993;17 : pp. 1254-60 .
35. Xie CI, Lin RC, Antony V, Lumeng L, Li TK, Mai K, Liu C, Wang QD, Zhao ZH, Wang GF. Daidzin an antioxidant isoflavonoid, decreases blood alcohol levels and shortens sleep time induced by ethanol intoxication. Alcohol Clin Exp Res. 1994 ; 18 : pp. 1443-7.
36. Lin RC, Guthrie S, Xie CY, Mai K, Lee DY, Lumeng L, Li TK. Isoflavonoid compounds extracted from pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism. Alcohol Clin Exp Res. 1996;20 : pp. 659-63.
37. Keung WM, Lazo O, Kunze L, Vallee BL. Potentiation of the bioavailability of daidzin by an extract of Radix puerariae. Proc Natl Acad Sci USA. 1996;93 : pp. 4284-8.
38. Shutt DA, Cox RI. Steroid and phyto-ostrogen binding to sheep uterine receptors in vitro. J Endocr. 1972;52:pp. 299-310.
39. Tang BY, Adams NR. Effect of equol on oestrogen receptors and on systhesis of DNA and protein in the immature rat uterus. J Endocr. 1980 ; 85 : pp. 291-7.
40. Xuan B, Zhou YH, Yang RL, Li N, Min ZD, Chiou GC. Improvement of ocular blood flow and retinal functions with puerarin analogs. J Ocul Pharmacol Ther. 1999;15 : pp. 207-16.
41. 陸曙、張寄南:中藥對心血管相關受體影響的研究現狀〔J〕,中國中西醫結合雜志,1998;18 : pp. 699。
42. Okamura N, Miki H, Orii H, Masaoka Y, Yamashita S, Kobayashi H, Yagi A. Simultaneous high-performance liquid chromatographic determination of puerarin, daidzin, paeoniflorin, liquiritin, cinnamic acid, cinnamaldehyde and glycyrrhizin in Kampo medicines. J. Pharm. Biomed. Anal. 1999 ; 19 : pp. 603-12.
43. Cao X, Tian Y, Zhang T, Li X, Ito Y. Separation and purification of isoflavones from Pueraria lobata by high-speed counter-current chromatography. J chromatogr A. 1999;855 : pp. 709-13.
44. 宋洪杰、曾明、胡晉紅、王大業、張澤明:葛屬植物中三種異黃酮成分分析,藥物分析雜誌,2000 ; 20 : pp 223-6.
45. Yasuda T, Kano Y, Saito K, Ohsawa K. Urinary and biliary metabolites of puerarin in rats. Biol Pharm Bull. 1995;18 : pp. 300-3.
46. Yasuda T, Kano Y, Saito K, Ohsawa K. Urinary and biliary metabolites of daidzin and daidzein in rats. Biol Pharm Bull. 1994;17 : pp. 1369-74.
47. Xu X, Harris KS, Wang HJ, Murphy PA, Hendrich S. Bioavailability of soybean isoflavone depends upon gut microflora in women. J Nutr. 1995 ; 125 : pp. 2307-15.
48. Adlercreutz H, Markkanen H, Watanabe S. Plasma concetration of phytoestrgen in Japanese men. Lancet 1993 ; 342 : pp. 1209-10.
49. Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G. Acute heart transplant rejection due to Saint John’s wort. Lancet. 2000;355 : pp. 548-9.
50. Johne A, Brockmoller J, Bauer S, Maurer A, Langheinrich M, Roots I. Pharnacokinetic interaction of digoxin with an herbal extract from St. John’s wort (Hypericum perforatum). Clin Pharmacol Ther. 1999;66 : pp. 338-45.
51. Hebert MF. Contributions of hepatic and intestinal metabolism and P-glycoprotein to cyclosporine and tacrolimus oral drug delivery. Advan Drug Delivery Rev. 1997;27 : pp. 201-214.
52. de Lannoy IA, Silverman M. The MDR1 gene product, P-glycoprotein, mediates the transport of the cardiac glycoside, digoxin. Biochem Biophys Res Commun. 1992;189:pp. 551-7.
53. Hodek P, Trefil P, Stiborová M. Flavonids-potent and versatile biologically active compounds interacting with cytochromes p450. Chem Biol Interac. 2002;139:pp. 1-21.
54. Di PA, Conseil G, Perez-Victoria JM, Dayan G, Baubichon-Cortaya H, Trompiera D, Steinfels E, Jault JM, de WH, Maitrejean M, Comte G, Boumendjel A, Mariotte AM, Dumontet C, McIntosh DB, Goffeau A, Castanys S, Gamarro F, Barron D. Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters. Cell Mol Life Sci. 2002 ; 59 : pp. 307-22.
55. Ikegawa T, Ohtani H, Koyabu N, Juichi M, Iwase Y, Ito C, Furukawa H, Naito M, Tsuruo T, Sawada Y. Inhibition of P-glycoprotein by flavonoid derivatives in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells. Cancer Lett. 2002 ; 177 : 89-93.
56. Castro AF, Altenberg GA. Inhibition of drug transport by genistein in multidrug-resistant cells expressing P-glycoprotein. Biochem Pharmacol. 1997 ; 53 : pp. 89-93.
57. Evans AM. Influence of dietary components on the gastrointestinal metabolism and transport of drugs. Ther Drug Monit. 2000 ; 22 : pp. 131-6.
58. Guerra MC, Speroni E, Broccoli M, Cangini M, Pasini P, Minghett A, Crespi-Perellino N, Mirasoli M, Cantelli-Forti G, Paolini M. Comparison between Chinese medical herb Pueraria Lobata crude extract and its main isoflavone puerarin Antioxidant properties and effects on rat liver CYP-catalysed drug metabolism. Life Sci. 2000 ; 67: pp. 2997-3006.
59. 謝文全:神農本草經 (古今功能輯注本),中國藥學研究所,台中1995;pp. 7。
60. 曾明、張澤明、鄭水慶、蘇中武:中藥葛根的本草學研究,中藥材,2000;23:pp. 46-8。
61. 那琦、謝文全:重輯名醫別錄,中國藥學研究所,台中1977;pp. 71-2。
62. 陶弘景:本草經集注 (輯校本) ,人民衛生出版社,北京 1994;pp. 271-2。
63. 孟譔、張鼎:食療本草,人民衛生出版社,北京 1984;pp. 6。
64. 唐慎微:重修政和經史証類備用本草,南天書局有限公司,台北 1976;pp. 196-7。
65. 李時珍:圖解本草綱目,文光圖書公司,台北 1970;pp. 740-2。
66. 岡西為人:重輯新修本草,國立中國醫藥研究所,台北 1964;pp. 200-1。
67. 那琦、謝文全、林麗玲:重輯本草拾遺,華夏文獻資料出版社,台中1988 ; pp. 84。
68. 謝文全、林豐定:重輯開寶重定本草,中國藥學研究所,台中 1998; pp. 106。
69. 劉文泰、王道純:本草品彙精要,南天書局有限公司,台北 1983;pp. 296。
70. 中華人民共和國藥典,化學工業出版社,北京 2000;pp. 273-4。
71. 季宇彬主編:中藥有效成分藥理與應用,黑龍江科學技術出版社,哈爾濱 1994;pp. 360-4。
72. The merck index 第十二版,pp. 475。
73. Kim DH, Yu KU, Bae EA, Han MJ. Metabolism of puerarin and daidzin by human intestinal bacteria and their relation to in vitro cytotoxicity. Bio Pharm Bull. 1998;21 : pp. 628-30.
74. Dennis J, Cada. Drug Facts and Comparisons, USA. 1999;pp. 3777-87。
75. Gerald K, McEvoy. AHFS Drug Information, USA. 2000;pp. 3374-89。
76. Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T. Human p-glycoprotein transports cyclosporin A and FK506. J Biol Chem. 1993;268:pp. 6077-80.
77. Barone GW, Gurley BJ, Ketel BL, Lightfoot ML, Abul-Ezz SR. Drug interaction between St. John''s wort and cyclosporine. Ann Pharmacother. 2000 ; 34 : pp. 1013-6.
78. Yee GC, McGurine TR. Pharmacokinetic drug interactions with cyclosporine. Clin Pharmacokinet. 1990 ; 19 : pp. 319-32, pp. 400-15.
79. Kane GC, Lipsky JJ. Drug-grapefruit juice interactions. Mayo Clin Proc. 2000 ; 75 : pp. 933-42.
80. Gerald K, McEvoy. AHFS Drug Information, U.S.A. 2000;pp. 1430-40.
81. Dennis J, Cada. Drug Facts and comparisons, U.S.A. 1999;pp. 747-56.
82. Cavet ME, West M, Simmons NL. Transport and epithelial secretion of the cardiac glycoside, digoxin, by human intestinal epithelial (Caco-2) cells. Br J Pharmacol. 1996;118:pp. 1389-96.
83. Fugh-Berman A. Herb-drug interactions. Lancet. 2000 ; 355 : pp.134-8.
84. Verschraagen M, Koks CH, Schellens JH, Beijnen JH. P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil. Pharmacol Res. 1999;40:pp. 301-6.
85. Fromm MF. P-glycoprotein : a defence mechanism limiting oral bioavailability and CNS accumulation of drugs. Int J Clin Pharm Ther. 2000;38:pp. 69-74.
86. Su SF, Huang JD. Inhibition of the intestinal digoxin absorption and exsorption by quinidine. Drug Metab Dispos. 1996;24:pp. 142-7.
87. Salphati L, Benet LZ. Effects of ketoconazole on digoxin absorption and disposition in rat. Pharmacology. 1998;56 : pp. 308-13.
88. Greiner B, Eichelbaum M, Fritz P, Kreichgauer HP, von Richter O, Zundler J, Kroemer HK. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest. 1999;104:pp. 147-53.
89. Cimino CO, Shelnutt SR, Ronis MJ, Badger TM. An LC-MS method to determine concentration of isoflavones and their sulfates and glucuronides conjugates in urine. Clinca Chimica Acta. 1999 ; 287 : pp. 69-82.
90. Thomas BF, Zeisel SH, Busby MG, Hill JM, Mitchell RA, Scheffler NM, Brown SS, Bloeden LT, Dix KJ, Jeffcoat AR. Quantitative analysis of the principle soy isoflavones genistein, daidzein and glycitein, and their primary conjugated metabolites in human plasma and urine using reversed-phase high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Biomed Sci Appl. 2001 ; 760 : pp. 191-205.
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