{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:47:48Z","timestamp":1779101268064,"version":"3.51.4"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":3843,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1994,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The use of zidovudine (AZT) for the treatment of acquired immunodeficiency syndrome (AIDS) induces a DNA\u2010depleting mitochondrial myopathy, which is histologically characterized by the presence of muscle fibers with \u201cragged\u2010red\u201d\u2013llike features, red\u2010rimmed or empty cracks, granular degeneration, and rods (AZT fibers). Because dysfunctioning muscle mitochondria may lead to defects of \u03b2\u2010oxidation of fatty acids, we examined the degree of neutral fat accumulation and muscle carnitine levels in the muscle biopsy specimens from 21 patients with AZT\u2010induced myopathic symptoms of varying severity. Six patients with no AZT fibers had normal endomyofibrillar lipid deposits and muscle carnitine levels; 7 patients with fewer than 5 AZT fibers per field had a mild (+) to moderate (++) increase in lipid droplets, and reduced muscle carnitine levels (3 patients); and 8 patients with more than 5 AZT fibers had severe muscle changes, a ++ to marked (+++) increase in lipid droplets, and reduced muscle carnitine levels (6 patients). Serial sections showed lipid globules often within \u201ccracks\u201d or vacuoles of the abnormal muscle fibers. We conclude that the muscle mitochondrial impairment caused by AZT results in (1) accumulation of lipid within the muscle fibers owing to poor utilization of long\u2010chain fatty acids, (2) reduction of muscle carnitine levels probably due to decreased carnitine uptake by the muscle, and (3) depletion of energy stores within the muscle fibers. The findings may have potential therapeutic implications in the treatment of AZT\u2010induced myopathic symptoms using oral carnitine supplementation.<\/jats:p>","DOI":"10.1002\/ana.410350418","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T16:00:17Z","timestamp":1104595217000},"page":"482-487","source":"Crossref","is-referenced-by-count":89,"title":["Zidovudine\u2010induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage"],"prefix":"10.1002","volume":"35","author":[{"given":"Marinos C.","family":"Dalakas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta E.","family":"Leon\u2010Monzon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isa","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl A.","family":"Jay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199004193221602"},{"key":"e_1_2_1_3_2","first-page":"645","article-title":"Inflammatory and toxic myopathies","volume":"5","author":"Dalakas MC","year":"1992","journal-title":"Curr Opin Neurol Neurosurg"},{"key":"e_1_2_1_4_2","volume-title":"Myology","author":"Dalakas MC","year":"1993"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410290607"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.8.1181"},{"key":"e_1_2_1_7_2","first-page":"145","article-title":"Prospective study of myopathy during prolonged low\u2010dose AZT: clinical correlates of AZT mitochondrial myopathy (AZT\u2010MM) and HIV\u2010associated inflammatory myopathy (HIV\u2010IM)","volume":"42","author":"Jay C","year":"1992","journal-title":"Neurology"},{"key":"e_1_2_1_8_2","doi-asserted-by":"crossref","first-page":"11934","DOI":"10.1016\/S0021-9258(18)80156-9","article-title":"Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti\u2010human immunodeficiency virus compound 2\u2032, 3\u2032\u2010dideoxycytidine","volume":"264","author":"Chen C\u2010H","year":"1989","journal-title":"J Biol Chem"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)91294-5"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(91)90112-3"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(91)90122-9"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02229156"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198412000-00021"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.30.8.795"},{"key":"e_1_2_1_15_2","volume-title":"Myology","author":"Engel AG","year":"1986"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111806"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410170602"},{"key":"e_1_2_1_18_2","first-page":"1663","volume-title":"Myology","author":"Engel AG","year":"1986"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00442676"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.410350418","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.410350418","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T14:37:31Z","timestamp":1698158251000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.410350418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,4]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1994,4]]}},"alternative-id":["10.1002\/ana.410350418"],"URL":"https:\/\/doi.org\/10.1002\/ana.410350418","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,4]]}}}