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    Severe lactic acidosis has been mainly reported with zidovudine (AZT), followed by stavudine (d5T), didanosine (ddI), and lamivudine (2TC) (43). Fialuridine Clinical trials testing the efficacy of fialuridine in patients with chronic hepatitis B were abruptly interrupted after several patients developed microvesicular steatosis and unmanageable lactic acidosis, sometimes with pancreatitis, neuropathy, or myopathy (44). Clinical manifestations of acquired mitochondrial cytopathies are extremely polymorphic.

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    Preclinical and clinical studies suggest a relationship between high anxiety-like states and greater alcohol intake , and as such, decreased CREB phosphorylation in the central nucleus of the amygdala may be responsible for increased anxietylike responses in alcohol-dependent animals, and thus increased drinking in dependent animals possibly through actions on the NPY system, which is a CREB target gene. Alcohol also has been shown to increase protein kinase activity in the nucleus accumbens after 12 weeks of chronic exposure but not after 1 or 5 weeks.

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