{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:10:27Z","timestamp":1790943027698,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,4,11]],"date-time":"2003-04-11T00:00:00Z","timestamp":1050019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2003,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The extent to which dense and irreversible sickle cells (ISCs) contribute to vaso\u2010occlusive episodes in sickle cell disease remains unclear.\n                    <jats:italic>N<\/jats:italic>\n                    \u2010Acetylcysteine (NAC) inhibits dense cell and ISC formation in sickle erythrocytes in vitro and restores glutathione levels toward normal. A phase II double\u2010blind randomized clinical trial was completed to determine the efficacy of NAC in decreasing dense cell and ISC formation, and vaso\u2010occlusive episodes in sickle cell disease. Twenty\u2010one subjects with a history of at least two vaso\u2010occlusive episodes per year and 6% dense cells were enrolled. Four treatment groups were analyzed; NAC at a dose of 2,400 mg per day decreased the percent dense cells from 20.1 \u00b1 2.9 to 12.6 \u00b1 2.1 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05) and increased red cell glutathione levels from 292.8 \u00b1 74.5 to 576.7 \u00b1 155.1 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). In addition, we observed a decrease in vaso\u2010occlusive episodes from 0.03 to 0.006 episodes per person\u2010days and a decreased in relative risk to\n                    <jats:italic>R<\/jats:italic>\n                    = 0.39. Although NAC did not significantly decrease the number of ISCs, there was a downward trend at all doses tested. In summary, NAC inhibited dense cell formation, restored glutathione levels toward normal, and decreased vaso\u2010occlusive episodes at a well\u2010tolerated dose of 2,400 mg per day. To determine the long\u2010term efficacy and safety of NAC, a multicenter phase III clinical trial is required. Am. J. Hematol. 73:26\u201332, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/ajh.10321","type":"journal-article","created":{"date-parts":[[2003,4,14]],"date-time":"2003-04-14T06:02:38Z","timestamp":1050300158000},"page":"26-32","source":"Crossref","is-referenced-by-count":98,"title":["Effects of\n                    <i>N<\/i>\n                    \u2010acetylcysteine on dense cell formation in sickle cell disease"],"prefix":"10.1002","volume":"73","author":[{"given":"Betty 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