Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly active antiretroviral therapy (HAART) can induce a characteristic lipodystrophy syndrome of peripheral fat wasting and central adiposity. HIV-1 protease inhibitors are generally believed to be the causal agents, although the syndrome has also been observed with protease-inhibitor-sparing regimens. Here, we postulate that the mitochondrial toxicity of the nucleoside-analogue reverse-transcriptase inhibitors plays an essential part in the development of this lipodystrophy, similar to the role of mitochondrial defects in the development of multiple symmetrical lipomatosis.
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PMID:Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. 1074 10

Effective therapies are now available that can stop the progression of HIV infection and significantly delay the onset of AIDS. The "highly active antiretroviral therapy" (HAART) is a combination of potent antiretroviral drugs such as viral protease inhibitors or nucleoside-analogue reverse-transcriptase inhibitors, that has a variety of serious side effects, including lipodystrophy, a pathology characterized by accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia, insulin resistance as well as fat wasting in face and limbs. There is still an open debate that concerns the precise responsibility of HAART as well as metabolic pathways and mechanisms that are involved in the onset of lipodystrophy. The similarities with multiple symmetric lipomatosis (MSL), in which mitochondria impairment plays a crucial role, lead to the hypothesis that drug-induced damages to mitochondrial DNA are able to alter mitochondria functionality to an extent that is similar to what occurs in MSL. In addition, several evidences indicate that HAART is also linked to a deregulated production of tumour necrosis factor-alpha, which uses mitochondria as intracellular targets. In this paper, we review data concerning the role of mitochondria in the pathogenesis of lipodystrophy, and advance a unifying hypothesis involving either direct or indirect effects of the drugs employed during HAART.
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PMID:Mitochondria in the pathogenesis of lipodystrophy induced by anti-HIV antiretroviral drugs: actors or bystanders? 1174 23

This study summarizes the adverse effects of antiretroviral therapy (ART) agents against HIV on orofacial health and health care. Current antiretroviral agents fall mainly into three major classes: nucleoside reverse-transcriptase inhibitors (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) - now with the new classes of fusion inhibitors, entry inhibitors--CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. Many of the ART agents can have adverse orofacial effects, or can give rise to allergies or drug interactions--the optimum anti-HIV drug has yet to be found. There are few orofacial adverse effects that characterize a particular ART class, but erythema multiforme (EM), ulcers and xerostomia may be associated with reverse-transcriptase inhibitors (RTI); parotid lipomatosis, taste disturbance, xerostomia and perioral paraesthesia mainly related to PIs. Facial lipoatrophy is a common adverse effect of NRTIs; EM is more frequently associated with NNRTIs. Thus, although most of the more recent ART drugs and combinations of them show improved safety profiles, some may give rise to orofacial adverse effects, and may affect oral health care.
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PMID:Antiretroviral therapy: effects on orofacial health and health care. 2353 Aug 6