Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fialuridine (FIAU, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil) is toxic to liver, heart, muscle, and nerve in clinical trials for chronic viral hepatitis (CH). Mitochondrial toxicity was hypothesized. To address pathophysiologic mechanisms, we examined mitochondrial changes in FIAU-treated woodchucks (WC) with CH from woodchuck hepatitis virus infection. WC (with and without CH from woodchuck hepatitis virus infection) were treated with FIAU (1.5 mg/kg/day) for 12 weeks. WC were killed. Liver, heart, skeletal muscle, and kidney samples underwent DNA extraction and were analyzed ultrastructurally (transmission electron microscopy). Myocardium, skeletal muscles, and liver samples were analyzed histologically. Abundance of hepatic, myocardial, muscle, and kidney mtDNA decreased in FIAU-treated WC, but the magnitude varied. mtDNA decreased 55% in heart, 65% in kidney, 74% in liver, and 87% in muscle (p < 0.02 for each tissue: FIAU-treated versus FIAU-untreated). Cellular damage was characterized ultrastructurally by mitochondrial enlargement, cristae dissolution, and lipid droplets. Lipid droplets found in the heart, diaphragm, biceps, and liver were sufficient to identify FIAU-treated WC (p < 0.05 each). Widespread mitochondrial damage to many tissues resulted from chronic FIAU treatment and occurred irrespective of CH. It manifested with mtDNA depletion, intracytoplasmic lipid droplets, and destroyed mitochondrial cristae. Defective mtDNA replication with mtDNA depletion seems central to the subcellular pathophysiology of altered energy metabolism and multiorgan failure in FIAU toxicity.
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PMID:Depletion of mitochondrial DNA, destruction of mitochondria, and accumulation of lipid droplets result from fialuridine treatment in woodchucks (Marmota monax). 901 Apr 51

The importance of vaccination against viral hepatitis, the virus's relationship to HIV, and each type of identified virus are explained. Additional information covers how each of the five types of hepatitis is transmitted. Particular attention is given to dual infection with HIV and hepatitis B, and ways hepatitis B can be treated and prevented. A side bar accompanying the article discusses the ultimate failure of Eli Lilly's drug Fialuridine as a treatment for hepatitis B.
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PMID:A, B, C, D, E...any school child can tell you not to mess with viral hepatitis. 1136 61