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  • Enhanced NF-κB expression induced by toxicants presumably modulates liver injury viagra canada generic through an effect on the synthesis of these mediators. Increased nuclear binding activity of the transcription factor AP-1 has also been described in the liver after treatment of animals with acetaminophen, carbon tetrachloride, or endotoxin. Similar effects have been described after treatment of animals with carbon tetrachloride, ethanol, endotoxin, or galactosamine (52–56).

    NF-κB is a ubiquitous transcription factor known to regulate the activity of numerous genes involved in inflammatory responses including inducible nitric oxide synthase , cyclooxygenase-3 , TNFα, and I-CAM-1. It has been suggested that this process involves inappropriate activation of biochemical signaling pathways in the cells leading to increased gene expression and inflammatory mediator production. This idea is supported by the findings that mice lacking the p30 subunit of NF-κB do not generate TNFα and are protected from carbon tetrachloride–induced toxicity (79).

    The fact that this activity is prevented by pretreatment of animals with gadolinium chloride demonstrates that Kupffer cells are crucial in the process. For example, following acetaminophen administration to animals, a rapid increase in nuclear binding activity of the transcription factor, NF-κB has been observed in the liver (61).

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    Annu Rev viagra canada generic Pharmacol Toxicol 1995. Metabolic polymorpshisms affecting activation of toxic and mutagenic arylamines. Immunological Mechanisms in Liver Injury 185 28. Bock KW.

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    B. Treatment Once a patient develops clinical hepatitis or the liver enzymes are raised 7 times normal, this mandates immediate stoppage of all potentially hepatotoxic drugs. However, regular once-a-month monitoring of LFT is recommended for older patients, patients with underlying liver diseases, patients with coexistent hepatitis B, C, or HIV infection, and malnourished patients because there are evidences that there is an increased risk of developing ATT-induced liver injury in these groups of patients. These recommendations are based on American Thoracic Society guidelines for managing patients with tuberculosis.

    A complete liver function profile should be carried out including prothrombin time.