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Branched chain amino acids (BCAAs) have been shown to affect gene expression, protein metabolism, apoptosis and regeneration of hepatocytes, and insulin resistance. They have also been shown to inhibit the proliferation of liver cancer cells in vitro, and are essential for lymphocyte proliferation and dendritic cell maturation. In patients with advanced chronic liver disease, BCAA concentrations are low, whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high, conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients. Based on these basic observations, patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines, with positive effects.

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The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILI based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILI, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILI involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.

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The tunneling conductance is calculated as a function of the gate voltage in wide temperature range for the single quantum dot systems with Coulomb interaction. We assume that two orbitals are active for the tunneling process. We show that the Kondo temperature for each orbital channel can be largely different. The tunneling through the Kondo resonance almost fully develops in the region T < ∼ 0.1T * K ∼ 0.2T * K , where T * K is the lowest Kondo temperature when the gate voltage is varied. At high temperatures the conductance changes to the usual Coulomb oscillations type. In the intermediate temperature region, the degree of the coherency of each orbital channel is different, so strange behaviors of the conductance can appear. For example, the conductance once increases and then decreases with temperature decreasing when it is suppressed at T = 0 by the interference cancellation between different channels. The interaction effects in the quantum dot systems lead the sensitivities of the conductance to the temperature and to the gate voltage. KEYWORDS: quantum dot, tunneling, Kondo effect, Coulomb oscillations §1. IntroductionCoulomb oscillations behavior in quantum dot systems is well known as one of the typical phenomena due to the Coulomb repulsion between electrons in the dot. But it is one aspect of the electron-electron interaction effects. Local spin moment is induced by the Coulomb repulsion in the dot sometime. It will fluctuate by exchanging spin moment with leads and thus cause the strong inelastic scattering. But the local spin disappears in the lowest temperature due to the spin singlet formation between leads and the dot. These effects have been investigated as the Kondo effect for the magnetic impurity systems in many years, 1) and for the quantum dot systems recently. 2,

Hepatitis C virus (HCV) is recognized as a major causative agent of parenterally transmittable non-A, non-B hepatitis. 1 HCV infection often persists for a long time and leads to chronic liver diseases; at least half of the HCV cases develop into chronic hepatitis, and 10% to 20% of cases develop into cirrhosis. 2 The high HCV mutation rate readily generates variants that contribute to establishing the persistent infection. 3

The liver experiences various changes with aging that could affect clinical characteristics and outcomes in patients with liver diseases. Both liver volume and blood flow decrease significantly with age. These changes and decreased cytochrome P450 activity can affect drug metabolism, increasing susceptibility to drug-induced liver injury. Immune responses against pathogens or neoplastic cells are lower in the elderly, although these individuals may be predisposed to autoimmunity through impairment of dendritic cell maturation and reduction of regulatory T cells. These changes in immune functions could alter the pathogenesis of viral hepatitis and autoimmune liver diseases, as well as the development of hepatocellular carcinoma. Moreover, elderly patients have significantly decreased reserve functions of various organs, reducing their tolerability to treatments for liver diseases. Collectively, aged patients show various changes of the liver and other organs that could affect the clinical characteristics and management of liver diseases in these patients.