Although antiviral agents have been adopted for the management of chronic hepatitis B, they have only limited efficacy because of the underlying impaired immune status. Propagermanium, a hydrophilic polymer of 3-oxygermyl propionate, has been reported to have potent immune modulatory activity associated with antiinflammatory and antineoplastic properties. For example, propagermanium augments lymphocyte functions in CD4 and CD8 cells, and in natural killer (NK) cells, and induces the production of several cytokines. A controlled pilot study of 16-week treatment with propagermanium for chronic hepatitis B (of moderate and mild grades on hepatic histology) revealed a sustained clearance of hepatitis B e (HBe) antigen and a favorable biochemical response at week 16 of treatment and at week 48 post-treatment. An open study also supported the clearance of hepatitis B virus from the blood and the possible improvement of histologic grading in the liver. There were few adverse events. A postmarketing survey, however, revealed the occurrence of moderate to severe liver damage after the treatment in about 4% of patients. Despite the exact nature of the liver damage being unclear, a putative cause is the swift removal of virus-infected hepatocytes by an immune reaction through the treatment. A subtle balance between host and viral conditions is the factor which most determines hepatitis B virus persistence. The rationale for a nonspecific immune modulator for the treatment of chronic hepatitis B will be the restoration of cellular immune responsiveness to viral infection. Although the cellular immunity for hepatitis B virus prior to the treatment should be studied, adequate observation of hepatic functions and viral markers in the recipients is clinically useful to predict liver failure during the treatment. In summary, the propagermanium regimen offers a potent and safe approach that is cost-effective for appropriate chronic hepatitis B patients with reserve hepatic capacity, and will provide new perspectives for immune therapy in chronic hepatitis B.

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The conversion of gamma-glutamylcysteinylethyl ester (gamma-GCE) to glutathione in a reduced form (GSH) was examined using isolated rat hepatocytes pretreated with diethylmaleate, a GSH-depletor. Incubation of hepatocytes with 0.1 and 5.0 mM gamma-GCE (gamma-GCE-hepatocytes) over a 30-min period resulted in time-dependent increases in intracellular GSH and nonprotein-SH (NP-SH) concentrations. Hepatocytes incubated with 5.0 mM but not 0.1 mM GSH over a period of 30 min showed a time-dependent increase in intracellular GSH concentration. In the gamma-GCE-hepatocytes pretreated with bis-(p-nitrophenyl)phosphate (BNPP), a non-specific esterase inhibitor, an enhancement of intracellular GSH concentration was markedly reduced. gamma-GCE concentration in the gamma-GCE-hepatocytes with BNPP pretreatment was significantly higher than that in the cells without BNPP pretreatment, although there was no difference in the total amount of intracellular NP-SH, i.e., gamma-GCE, GSH, gamma-glutamylcysteine, cysteine ethyl ester, and cysteine between both gamma-GCE-hepatocytes. The present results indicate that gamma-GCE is transported into liver cells more easily than GSH itself, resulting in its conversion to GSH via esterase and glutathione synthetase within the cells.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease guidelines recommended a forced expiratory volume at one second per forced vital capacity as a standard diagnostic criterion of chronic obstructive pulmonary disease (COPD). A few reports on the risk factors of COPD have used the standard diagnostic criteria. In our study, the effects of age and smoking on COPD in Japan under the standard diagnosis criteria were evaluated. METHODS: Subjects were 11,460 participants aged 25-74 years during health check-ups including spirometry at the Toyota Community Medical Center in Japan. Logistic regression analyses with or without COPD as a dependent variable and age as an independent variable were conducted among non-smokers. The ratio of the observed number of COPD cases in former and current smokers to the number expected for non-smokers with the same distribution of age (O/E) was calculated. RESULTS: The proportion of males incurring COPD significantly increased with age, and the O/E for former and current male smokers was significantly higher than one, i.e., O/E (95% confidence interval) for current smokers with a Brinkman Index of <400, 400-799, and 800+ were 3.10 (2.00-4.81), 2.78 (2.05-3.73), and 4.76 (3.65-6.19), respectively. Among females, the O/E for current smokers with a Brinkman Index of <400, and 400-799 were significantly higher than one. CONCLUSION: Age and smoking were shown to constitute strong risk factors for COPD under the standard diagnostic criteria.

Abstract:We herein report the case of a 31-year-old Japanese woman who developed adult-onset clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and presented with consciousness disorder and olfactory disturbance secondary to influenza A infection. The patient's neurological symptoms and the lesion in the splenium resolved within 14 days without therapy. Magnetic resonance images and the clinical course were consistent with a diagnosis of MERS; however, mental changes following the influenza infection always present a diagnostic dilemma for physicians. We considered various diagnoses, including viral encephalitis, medication-related encephalopathy, and MERS. A comprehensive assessment may be required to diagnose MERS, since it may mimic other neurological diseases, such as viral encephalitis and medicationrelated encephalopathy.Key words: mild encephalitis/encephalopathy with a reversible splenial lesion, influenza, olfactory disorder