Medicine of the Future in America

Category Archives: Interferon-alpha - Part 2

Interferon-alpha-induced changes in metallothionein expression: Patients

Twenty-one patients with chronic HCV infection who underwent liver biopsy both before and after IFN-alpha therapy were selected to participate in the present study. The second biopsy was performed approximately one year after the completion of IFN-alpha therapy. The diagnosis of chronic HCV infection was based on abnormal serum alanine aminotransferase levels for more than six months. The patients were positive for HCV antibody (second-generation test, ELISA) and HCV RNA (reverse transcription-polymerase chain reaction). The standard protocol for IFN-alpha therapy was as follows: 6 MU to 10 MU of IFN-alpha daily for the first two weeks then three times a week for 22 weeks. Continue reading

Interferon-alpha-induced changes in metallothionein expression (Part 3)

viral eliminationModern treatment regimens result in viral elimination in 60% of individuals. A variety of viral and host factors, such as HCV RNA titre, HCV genotype and the presence of cirrhosis, have been shown to affect the response to IFN-alpha therapy. MT was among the first genes to be identified as an IFN-alpha/beta-induced gene. A putative IFN-stimulated response element is present in the promoter region of MT genes. Recently, Carrera et al proposed the hepatic MT level as a biological factor associated both with the severity of HCV infection and with a better response to IFN therapy. Continue reading

Interferon-alpha-induced changes in metallothionein expression (Part 2)

On the other hand, low concentrations of hydrogen peroxide suppressed HCV RNA replication in hepatoma cells. Thus, the relationship between oxidative stress and HCV replication has yet to be determined. MT was originally discovered as a class of small and cysteine-rich proteins that participate in detoxification of heavy metals and in the absorption, storage and homeostasis of essential trace elements. Accumulated evidence indicates a significant role for MT in the maintenance of redox balance, scavenging free radicals, and in controlling the activity of zinc-containing enzymes. Continue reading

Interferon-alpha-induced changes in metallothionein expression (Part 1)

viral infectionsOxidative stress has been implicated in the pathogenesis of certain viral infections; in particular, hepatitis C virus (HCV), which can result in chronic hepatitis and subsequently lead to liver cirrhosis and hepatocellular carcinoma. The precise mechanisms underlying HCV-associated liver cell injury are not well known, but oxidative stress, imposed either directly by the virus or by the host-immune response, has been postulated as a potential mechanism of pathogenesis of HCV infection. A positive correlation between oxidative stress and histological disease pattern has been demonstrated in the livers of patients infected with HCV. Continue reading

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