Iron overload is associated with hepatic oxidative damage to DNA in nonalcoholic steatohepatitis.

Several lines of evidence have suggested that oxidative stress plays an important role for the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, by using immunohistochemical staining of liver biopsy samples, we measured hepatic 7,8-dihydro-8-oxo-2' deoxyguanosine (8-oxodG), a DNA base-modified product generated by hydroxyl radicals, of 38 NASH patients and compared with 24 simple steatosis and 10 healthy subjects. Relation of hepatic 8-oxodG with clinical, biochemical, and histologic variables and changes after iron reduction therapy (phlebotomy plus iron-restricted diet) were also examined.

Ultrastructural demonstration of hepatitis B virus production in a mouse model produced by hydrodynamic transfection.

A mouse model of hepatitis B virus (HBV) infection produced by hydrodynamic injection of HBV DNA has been recently established. However, the ultrastructural demonstration of HBV particles in this mouse model has not as yet been reported. In our study, plasmid DNA containing wild-type HBV DNA was rapidly injected into 8-week-old female SCID mice via the tail vein.

Hepcidin expression in the liver: relatively low level in patients with chronic hepatitis C.

Patients with chronic hepatitis C frequently have serum and hepatic iron overload, but the mechanism is unknown. Recently identified hepcidin, exclusively synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. This study was conducted to determine the hepatic hepcidin expression levels in patients with various liver diseases.

Unidentified virus-like particles are detected in plasmas with elevated ALT levels: are they significant of etiological agent(s) of non-B, non-C hepatitis?

GB virus C (GBV-C) and hepatitis G virus (HGV) have been proposed as new viruses etiologically implicated in non-B, non-C hepatitis, but the morphology of these particular virus particles is still unknown, and most cases of non-A to E hepatitis do not relate to their infections. We tried to visualize virus-like particles (VLPs) in plasma samples from hepatitis B surface antigen- and antibody to hepatitis C virus (HCV)-negative blood donors with elevated alanine aminotransferase (ALT), and examined the association of the virus-like particles and the genomes of parenterally transmissible GBV-C/HGV. Twenty-three plasma samples, 13 with elevated ALT levels and 10 with normal ALT values, from blood donors without infections of hepatitis B virus (HBV) and HCV, were subjected to a 20%-60% sucrose density gradient centrifugation, and virus-like particles were observed by electron microscopy.

Increased lipid peroxidation in patients with non-alcoholic fatty liver disease and chronic hepatitis C as measured by the plasma level of 8-isoprostane.

Background: Oxidative stress plays an important role in the pathogenesis of chronic liver diseases. The plasma level of 8-isoprostane, a product of lipid peroxidation, is a marker of oxidative stress in vivo. The aim of the present study was to clarify whether the degree of lipid peroxidation, as measured by the plasma level of 8-isoprostane, influences the progression of chronic liver diseases and hepatocarcinogenesis.

siRNA-resistance in treated HCV replicon cells is correlated with the development of specific HCV mutations.

RNA interference (RNAi) has been extremely effective against hepatitis C viral (HCV) gene expression in short-term cell culture. Our aim was to determine whether long-term RNAi might result in HCV-resistant mutants. Huh7 HCV subgenomic replicon cells were transfected with short interfering RNAs (siRNAs).

The ultrastructural morphology of native hepatitis B virus.

Cell lines (2.2.15 cells) capable of supporting the replication of hepatitis B virus (HBV) DNA and intact viral particles have been established by HBV DNA transfection into HepG2 cells.

Morphological identification of hepatitis C virus E1 and E2 envelope glycoproteins on the virion surface using immunogold electron microscopy.

It is known that hepatitis C virus (HCV) particles are spherical, 55-65 nm particles with fine surface projections of about 6 nm in length and with a 30-35 nm inner core. We have reported that free HCV particles labeled with gold particles specific to the HCV E1 glycoprotein are located in 1.14-1.

Lactoferrin inhibits lipid peroxidation in patients with chronic hepatitis C.

Lactoferrin is a milk protein with inhibitory effect on lipid peroxidation induced by oxidative stress. Oxidative stress plays an important role in the pathogenesis of chronic hepatitis C (CHC). The aim of this study was to evaluate the effect of bovine lactoferrin (bLF) monotherapy on lipid peroxidation, hepatic inflammation and iron metabolism in patients with CHC.

Morphology of hepatitis C and hepatitis B virus particles as detected by immunogold electron microscopy.

We performed indirect immunogold electron microscopy (EM) for immunological identification and characterization of hepatitis C virus (HCV). To clarify the morphology of HCV, an indirect immunogold EM of two plasma samples from patients with high HCV RNA titers was carried out using antibodies specific for the putative HCV envelope protein (E) 1. Spherical virus particles 55-65 nm in diameter with delicate spike projections were detected in the 1.

Circulating level of large splice variants of tenascin-C is a marker of piecemeal necrosis activity in patients with chronic hepatitis C.

Background: It has been reported that histological activity index and piecemeal necrosis are good factors to evaluate the prognosis in patients with chronic hepatitis C (CHC). Thus, there is a need for simple and noninvasive means to assess disease activity and piecemeal necrosis in patients with CHC. In this study, we measured the serum concentrations of large splice variants of tenascin-C (cTN-C) in patients with CHC, and examined their correlation with the degree of inflammatory activity and fibrosis as evaluated in liver biopsy specimens.

Accumulation of 8-nitroguanine in the liver of patients with chronic hepatitis C.

Background/aims: Nucleic acid damage by reactive nitrogen and oxygen species may contribute to inflammation-related carcinogenesis. To investigate the extent of nucleic acid damage in hepatitis C virus infection and its change after interferon treatment, we measured 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the liver of patients with chronic hepatitis C (CHC) before and after interferon therapy.

Methods: Hepatic accumulation of 8-nitroguanine and 8-OHdG was immunohistochemically evaluated in 20 CHC patients and 7 control patients with non-alcoholic fatty liver.

[Present and future situations of support systems for the treatment of alcohol dependence].

In 1996, Mie Association for the Study of Alcohol-related Diseases (MASAD) started, which was consisted of 21 hospitals and have been conducted by managers constituted of doctors, nurses, and medical social workers with following backgrounds. Before the opening, there were a small number of physicians who recognized necessity for cooperative medical care of alcohol dependence, whereas the ratio of alcoholics to inpatients of general hospitals was 17.8%.

Different hepatitis C virus dynamics of free-virions and immune-complexes after initiation of interferon-alpha in patients with chronic hepatitis C.

Background/aims: To elucidate the mechanisms of action of interferon (IFN) against hepatitis C virus (HCV), we studied the serum HCV dynamics of free-virions (FV) and immune-complexes (IC) in patients treated with IFN.

Methods: FV and IC were separated by immunoprecipitation using anti-human immunoglobulin and quantified serially using real-time detection-polymerase chain reaction.

Results: Initially [1st phase (0-24 h)], the FV decreased more rapidly compared to IC [exponential decay slope (EDS)=1.

Twice-a-day versus once-a-day interferon-beta therapy in chronic hepatitis C.

Background/aims: The intravenous administration of interferon-beta may be effective for the treatment of chronic hepatitis C, as is intramuscular interferon-beta. We compared the efficacy and safety of twice-a-day versus once-a-day of natural interferon-beta for the initial treatment of patients with chronic hepatitis C.

Methodology: Forty-nine patients with chronic hepatitis C, with less than 5 Meq/mL serum hepatitis C virus-RNA, were randomly assigned into one of the two treatment groups A and B and treated with natural interferon-beta following two different protocols.

Nonimmune complexed HCV RNA titer in serum as a predictor of interferon response in patients with chronic hepatitis C.

Objective: Hepatitis C virus (HCV) has been reported to exist in the circulation of patients in various forms such as free virions, immune complexes, and nucleocapsids. To clarify the clinical significance of serum HCV titers according to the forms of virus particles, we evaluated the immune complexed (IC) and nonimmune complexed (NIC) HCV RNA titers in 77 chronic hepatitis patients treated with interferon (IFN).

Methods: IC and NIC forms in pretreatment serum were separated by immunoprecipitation using antihuman immunoglobulin antibody, and quantified by reverse transcription polymerase chain reaction.

Dietary iron restriction improves aminotransferase levels in chronic hepatitis C patients.

Background/aims: It is generally accepted that iron overload plays an important role in the pathogenesis of liver cell injury in chronic hepatitis C. The present study was undertaken to evaluate whether low-iron diet improves liver function tests in patients with chronic hepatitis C.

Methodology: Seventeen patients with chronic hepatitis C (13 men and 4 women, 54 +/- 14 years old) that did not respond to, or were unsuitable for interferon therapy, were enrolled in this study.

Early diagnosis of hepatocellular carcinoma using a sensitive assay for serum des-gamma-carboxy prothrombin: a prospective study.

Background/aims: Measurement of des-gamma-carboxy prothrombin by conventional methods is of limited use for the early detection of hepatocellular carcinoma for its low sensitivity. The aim of the present study was to investigate the usefulness of measuring des-gamma-carboxy prothrombin by a highly sensitive assay for the early diagnosis of hepatocellular carcinoma in patients with chronic liver disease and for the detection of recurrence after treatment of hepatocellular carcinoma.

Methodology: Des-gamma-carboxy prothrombin levels by a sensitive assay and alpha-fetoprotein levels were sequentially measured in 188 patients with type B or C chronic liver disease and in 63 patients with hepatocellular carcinoma.

Asymmetric Electroreduction of Ketone and Aldehyde Derivatives to the Corresponding Alcohols Using Alcohol Dehydrogenase as an Electrocatalyst.

Asymmetric electroreduction of ketone and aldehyde derivatives was examined for two electrochemical reduction systems using alcohol dehydrogenase (ADH) as an electrocatalyst. The reaction system A is concerned with reduction of substrates catalyzed by ADH coupled with regeneration of cofactors by another enzyme with assistance of methyl viologen as an electron mediator, and the reaction system B is concerned with the use of ADH as the sole enzyme which catalyzes both reduction of substrates and regeneration of cofactors. In the latter case, a redox couple of phenethyl alcohol/acetophenone is used as an electron mediator to induce the reaction.