{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T15:18:16Z","timestamp":1760368696841},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,11]],"date-time":"2006-07-11T00:00:00Z","timestamp":1152576000000},"content-version":"vor","delay-in-days":4362,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[1994,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Blackfoot disease is a peripheral vascular disease causally related to the fluorescent humic acid found in the drinking water of endemic areas in Taiwan. We compared the effects of humic acid (HA) purified from the well water of Blackfoot disease endemic areas with the effects of commercial humic acid (Aldrich) as well as trivalent arsenic (As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>) on protein C activity, which plays an important role in regulation of blood coagulation and fibrinolysis. Humic acid, either purified from drinking water or obtained commercially, dose\u2010dependently inhibited both activated protein C activity and the activation of protein C induced by Protac, a snake venom\u2010derived protein C activator. In contrast to humic acid, arsenic oxide dose\u2010dependently enhanced both activated protein C activity and the Protac\u2010stimulated activation of protein C. In the presence of humic acid the enhancement effect of arsenic oxide was completely abolished, resulting in concentration\u2010dependent inhibition of protein C activity. Therefore, the results of this study indicate that humic acid is a potent protein C inhibitor even in the presence of arsenic, which enhances the protein C activity. Since protein C is a potent anticoagulant and profibrinolytic agent, acquired defects of protein C induced by humic acid might cause a thrombophilic or hypercoagulable state. Whether this is one of the possible mechanisms of humic acid\u2010induced thrombotic disorders in Blackfoot disease needs to be further characterized. \u00a9 1994 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.2830460403","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T13:42:43Z","timestamp":1172065363000},"page":"264-269","source":"Crossref","is-referenced-by-count":15,"title":["Plasma protein c activity is enhanced by arsenic but inhibited by fluorescent humic acid associated with blackfoot disease"],"prefix":"10.1002","volume":"46","author":[{"given":"Hsin\u2010Ling","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu\u2010Chin","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fung\u2010Jou","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Chong","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,11]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"25","article-title":"A pathological study on the blackfoot disease in Taiwan","volume":"14","author":"Yeh S","year":"1963","journal-title":"Rep Inst Pathol National Taiwan University"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.1984.tb01489.x"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.1990.tb01703.x"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a115439"},{"key":"e_1_2_1_6_2","first-page":"66","article-title":"Studies on fluorescent compounds in water of a well in Blackfoot disease endemic areas in Taiwan: Humic substances","volume":"87","author":"Lu FJ","year":"1988","journal-title":"J Formosan Med Assoc"},{"key":"e_1_2_1_7_2","first-page":"352","article-title":"Fluorescent compounds in drinking water of Blackfoot disease endemic areas: Animal experimental model","volume":"85","author":"Lu FJ","year":"1986","journal-title":"J Formosan Med Assoc"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91629-O"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/aoc.590040304"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(93)90011-C"},{"key":"e_1_2_1_11_2","first-page":"884","article-title":"The fluorescent compounds from drinking water and the vascular disorders of Blackfoot disease","volume":"523","author":"Chiu HC","year":"1991","journal-title":"FASEB"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0278-2391(88)90189-9"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198308113090604"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)90494-9"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac50047a044"},{"key":"e_1_2_1_16_2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0021-9258(17)33886-3","article-title":"A new vitamin K\u2010dependent protein","volume":"251","author":"Stenflo JA","year":"1976","journal-title":"J Biol Chern"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00645a029"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V59.5.1067.1067"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00544a001"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(73)90123-0"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110368"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111632"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110385"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V64.6.1297.1297"},{"key":"e_1_2_1_25_2","first-page":"314","article-title":"Studies of fluorescent compounds in drinking water of blackfoot disease endemic areas. 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