The prevalence of metabolic syndromes has increased dramatically in both Western and Asian countries, and nonalcoholic fatty liver disease (NAFLD) has recently emerged as a major health issue. Excess fructose intake is a progressive factor in the pathophysiology of NAFLD. In this study, we aimed to analyze the effects of fructose on hepatocytes during lipotoxicity. The effects of fructose were assessed in mice fed a high-fat diet with/without sucrose (HFDS/HFD) and in HepG2 cells. Mice fed HFDS showed advanced liver fibrosis as compared with mice fed HFD or normal chow. Hemoxygenase-1 expression was significantly increased in the livers of HFDS-fed mice. In MTT assays, oleate induced cell death in HepG2 cells treated with fructose-supplemented Dulbecco’s modified Eagle’s medium (DMEM). Although oleate did not cleave Caspase 3, oleate increased necrotic cell death in HepG2 cells cultured in fructose-supplemented DMEM. Oleate in fructose-supplemented DMEM significantly increased the number of reactive oxygen species (ROS)-positive hepatocytes. N-acetyl cysteine ameliorated oleate-induced ROS production and cell death. Although unsaturated fatty acids are less lipotoxic fatty acids, excess fructose can promote unsaturated fatty acid toxicity via ROS production.

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Immune thrombocytopenia (ITP) is characterized by increased platelet destruction and reduced platelet production, mediated by antiplatelet autoantibodies. Owing to the absence of definitive tests, diagnosis of ITP mainly involves exclusion of other thrombocytopenic disorders. Accumulating evidence has implicated enhanced autophagy in thrombopoiesis and ITP. However, it remains unknown whether platelet autophagy is enhanced in patients with ITP and has diagnostic potential. To determine this, we measured the proportion of autophagosome-rich platelets (ARPs%) in patients with thrombocytopenia, including ITP. We examined 34 patients with ITP and 52 patients with other types of thrombocytopenic disorders. To detect and quantify autophagosomes within platelets, we used flow cytometry with a cationic fluorescence dye, Cyto-ID, which specifically labels autophagic compartments. Among thrombocytopenic patients, ARPs% was significantly elevated only in ITP patients (p ‹ 0.01) and was found to be significantly correlated with the proportion of reticulated platelets (RPs%) (r = 0.58) and mean platelet volume (r = 0.55). ARPs% showed a greater sensitivity but reduced specificity (88.2% and 71.2%, respectively) compared with those of RPs% (85.3% and 90.4%, respectively). These data suggest that enhanced autophagy of platelets is a characteristic finding in patients with ITP and shows diagnostic potential in thrombocytopenia.

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In this study, we aimed to clarify the outcome a change of treatment due to diagnosis change to bipolar disorder (BD) in patients who had been treated for major depressive disorder (MDD). A mirror image study was conducted in 66 BD patients who had been treated for MDD for more than one year. Setting the date of changing diagnosis as a mirror date, the number of mood episodes observed within 12 months before and after the mirror date, history of hospitalization, and history of suicide attempt were compared in these patients. The subjects were divided into the improved group (n=36) and non-improved group (n=30), and intergroup comparisons were made on patients’ attributes, items associated with mood disorders, and drugs prescribed for 6 and 12 months before and after the mirror date. The number of mood episodes after changing the diagnosis to BD as well as the percentage of patients with a history of suicide attempt decreased significantly. According to the results of a multivariate analysis, family history of psychiatric disorders was a related factor in the improved group. It is important to identify BD patients who have been treated for MDD and to adequately treat them.

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