Elevated iron levels have been associated with raised serum alanine transaminase (ALT) levels in hepatitis C virus (HCV)-infected humans. However, it is not clear if HCV infection causes increased iron accumulation by the liver or if the severity of HCV infection is actually worsenedby higher iron levels in the host. To better understand the relationship between iron and persistent HCV infections, we examined the effect of excess dietary iron on disease severity in HCV-infected chimpanzees. Iron was supplemented in the diets of four HCV-infected and two uninfected chimpanzees for 29 weeks to achieve iron loading. Iron loading was confirmed by increases in serum iron levels, percentages of transferrin saturation, ferritin levels, elevations in hepatic iron concentration (HIC), and by histological examination. The majority of HCV-infected chimpanzees had higher iron levels before iron feeding than the uninfected animals. Hepatitis C virus (HCV) infections are a significant health problem worldwide. HCV infections are particularly problematic as a result of the high rate of chronicity. Persistent infection has been estimated to occur in approximately 85% of HCV-infected individuals. 1-3 Individuals with persistent HCV infection may develop cirrhosis and hepatocellular carcinoma, usually after several decades. 1,3 The transmission of HCV is primarily associated with percutaneous routes 4 and is commonly associated with injection drug use. However, the route of transmission for many HCV infections is unclear, because risk factors are not always identified. Although recipients of blood transfusions were at risk for acquiring HCV in the past, obligatory anti-HCV screening of blood donors has significantly decreased this risk. Other routes of infection may include sexual and perinatal transmission. However, the significance of these routes is unclear, and the efficiency is very low compared with hepatitis B virus or human immunodeficiency virus.The pathogenesis of hepatitis C has been difficult to study because of the lack of small animal models and conventional tissue culture systems. These obstacles have hindered the development of vaccines and antiviral treatments. Current antiviral treatments are associated with unpleasant side effects and are ineffective in the majority of HCV-infected patients. 1 Treatments for chronic HCV infection include interferon alfa (IFN-␣) alone or in combination with ribavirin. The majority (80%-85%) of patients fail to normalize serum alanine transaminase (ALT) and lose HCV RNA in the serum at 6 months' posttreatment when treated with IFN-␣ alone. The combination of IFN-␣ and ribavirin is more promising, because 40% to 50% of individuals experience a sustained response. 1 Iron reduction therapy is under investigation as a potential approach to lessening the severity of HCV infections. Elevated serum iron, transferrin saturation, and ferritin levels are often observed in individuals with chronic HCV infection, and although few have severe hepatic iron overload, a high percentage of indivi...
Erythrocyte spectrin, isolated by aqueous extraction of erythrocyte ghosts, may be freed from contaminating membrane lipids and small amounts of other proteins by gel chromatography in 5 or 10 mM deoxycholate. The purified protein, in deoxycholate, is a mixture of monomers and dimers, both highly asymmetric molecules. The hydrodynamic properties of the dimer closely resemble those of muscle myosin, and spectrin and myosin also have similar circular dichroism spectra. The proportion of dimer to monomer in the purified protein varies from one preparation to another, an observation for which there is no simple explanation. In the absence of deoxycholate, spectrin associated beyond the dimer stage, possibly by loose end-to-end aggregation involving hydrophobic forces.
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