Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report investigates the pathomechanism of acute renal failure caused by toxic acute tubular necrosis after treatment with the antiretroviral agent adefovir. A 38-year-old white homosexual man with human immunodeficiency virus infection and no history of opportunistic infections was maintained on highly active antiretroviral therapy (HAART), including hydroxyurea, stavudine, indinavir, ritonavir, and adefovir dipivoxil. Histologic examination of the renal biopsy showed severe acute tubular degenerative changes primarily affecting the proximal tubules. On ultrastructural examination, proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Functional histochemical stains for mitochondrial enzymes revealed focal tubular deficiency of cytochrome C oxidase (COX), a respiratory chain enzyme partially encoded by mitochondrial DNA (mtDNA), with preservation of succinate dehydrogenase, a respiratory chain enzyme entirely encoded by nuclear DNA (nDNA). Immunoreactivity for COX subunit I (encoded by mtDNA) was weak to undetectable in most tubular epithelial cells, although immunoreactivities for COX subunit IV and iron sulfur subunit of respiratory complex III (both encoded by nDNA) were well preserved in all renal tubular cells. Single-renal tubule polymerase chain reaction revealed marked reduction of mtDNA in COX-immunodeficient renal tubules. We conclude that adefovir-induced nephrotoxicity is mediated by depletion of mtDNA from proximal tubular cells through inhibition of mtDNA replication. This novel form of nephrotoxicity may serve as a prototype for other forms of renal toxicity caused by reverse transcriptase inhibitors.
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PMID:Adefovir nephrotoxicity: possible role of mitochondrial DNA depletion. 1209 87

Patients with HIV (human immunodeficiency virus) experience multiple signs and symptoms that accompany the progress of HIV-related diseases. HIV-related symptoms are associated with side effects and HAART (highly active antiretroviral therapy) complications. The purposes of this study were to estimate the frequency and intensity of HIV-related signs and symptoms in patients with HIV infection and to explore relationships between HIV-related symptoms and the HAART regimen. Data on a total of 172 HIV-positive patients enrolled in an HIV case management program were analyzed for this study. Participants experienced an average of 9.73+/-7.27 symptoms, with fatigue, dry mouth and weakness the most frequently reported. Average mean symptom intensity among participants was 13.24+/-11.48. Insomnia, depression and disorientation were the most severe symptoms. No differences were recorded between HIV-related symptoms and disease progression. Fatigue intensity showed significant differences between NRTI (nucleoside reverse transcriptase inhibitors), +NNRTI (non-nucleoside reverse transcriptase inhibitors) and NRTI+PI (protease inhibitors) based regimens (p=.03). In addition, cluster symptoms of confusion/distress among participants without HAART had a significantly higher mean intensity than those with HAART (t=2.0, df=1, p=.04). Our study indicated that symptom management for fatigue and early detection of psychological distress is needed to improve quality of life for people living with HIV/AIDS.
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PMID:[HIV-related symptoms in patients with HIV infection enrolled in an HIV case management program in Taiwan]. 1922 99