Document 0026
 DOCN  M9460026
 TI    Schwann cell mitochondrial alterations in peripheral nerves of rabbits
       treated with 2',3'-dideoxycytidine.
 DT    9404
 AU    Feldman D; Anderson TD; Department of Investigative Toxicology,
       Hoffmann-La Roche Inc.,; Nutley, NJ 07110.
 SO    Acta Neuropathol (Berl). 1994;87(1):71-80. Unique Identifier : AIDSLINE
       MED/94189276
 AB    2',3'-Dideoxycytidine (ddC) is a nucleoside analogue and
       reverse-transcriptase inhibitor that is approved for treatment of AIDS
       patients. A rabbit model of ddC neurotoxicity was developed to help
       understand the dose-limiting clinical neurotoxicity of ddC. Rabbits with
       a myelinopathy resulting from treatment with ddC exhibited mitochondrial
       alterations in Schwann cells of sciatic and tibial nerves and dorsal
       root ganglia. These changes were initially evident after 16 weeks of
       oral treatment with 35 mg/kg per day of ddC and were positively
       correlated with myelin pathology in individual animals. Cup-shaped
       mitochondria were frequently observed; when these mitochondria occurred
       in multiple concentric arrays or at various angles to one another,
       different profiles were formed depending on the plane of section. An
       increased number of mitochondrial cristae assumed a tubular
       configuration. It is suggested that the complex aggregations of
       mitochondria seen in this experiment are an adaptive response to altered
       mitochondrial function caused by treatment with ddC.
 DE    Acquired Immunodeficiency Syndrome/DRUG THERAPY  Animal  Ganglia,
       Spinal/DRUG EFFECTS/*PATHOLOGY/ULTRASTRUCTURE  Human  Microscopy,
       Electron  Mitochondria/DRUG EFFECTS/*PATHOLOGY/ULTRASTRUCTURE
       Neurotoxins/*TOXICITY  Rabbits  Reference Values  Schwann Cells/DRUG
       EFFECTS/*PATHOLOGY/ULTRASTRUCTURE  Sciatic Nerve/DRUG
       EFFECTS/*PATHOLOGY/ULTRASTRUCTURE  Tibial Nerve/DRUG
       EFFECTS/*PATHOLOGY/ULTRASTRUCTURE  Zalcitabine/*TOXICITY  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).