Four patients treated with the herbal medicine syo-saiko-to (xiao-chai-hu-tang) exhibited acute drug-induced liver injury. The latent period was one and a half to three months. All of the patients showed a rise in aminotransferases after readministration or challenge test. The liver histology revealed centrilobular confluent necrosis or spotty necrosis, microvesicular fatty change, acidophilic degeneration, and a granuloma. Cholestasis was seen in two patients. The results of the [13C]aminopyrine breath test, performed in one patient, were low before the challenge test and even lower after the challenge. These findings suggest that the herbal medicine syo-saiko-to may induce acute injury or the hepatocellular pattern with variable cholestasis.
Proton nuclear magnetic resonance (1H-NMR) has been utilized for qualitative and quantitative measurement of the components of nonhomogeneous biological specimens, as it can analyze sensitively the chemical structure of organic compounds without pretreatment of the materials. Levels of lactate in serum and bile were measured by 1H-NMR in healthy volunteers and patients with non-malignant or malignant diseases of the liver and biliary tract, and the usefulness of such measurements for the diagnosis of hepatobiliary malignancies was determined. The mean (+/- SD) serum lactate levels were 0.52 +/- 0.33 mmol/l in five healthy volunteers, 1.38 +/- 1.59 mmol/l in 30 patients with non-malignant diseases and 2.95 +/- 2.00 mmol/l in 21 patients with malignant diseases, the differences among the three groups being significant. Biochemical enzymatic measurement of serum lactate levels revealed no such difference. In bile, the spectrum of lactate was observed in all of 16 patients with malignant diseases, but in none of two healthy volunteers and 12 patients with non-malignant diseases. The mean time required for the measurement was 36.77 min for serum and 6.40 min for bile. The measurement of lactate levels in serum and bile using 1H-NMR may be useful for the detection of hepatobiliary malignancies.
P0 glycoprotein in bovine peripheral nerve myelin was solubilized in 0.1% triethylamine and digested with trypsin. The tryptic peptides were separated into 12 peaks by high performance liquid chromatography (HPLC) using a nonionic macroreticular polystyrene resin, Hitachi 3013. In addition to the amino terminal and the carbohydrate-linked peptide, four fatty acid-linked peptides were obtained. The fatty acid-linked peptides contained 0.9 mol fatty acids per molecule. The relative molar ratio of palmitate, stearate and oleate linked to the peptide was 8, 3 and 2. The site of esterification of P0 protein appears to be close to the membrane, because the fatty acid-linked peptides included a highly hydrophobic domain. In spite of heterogeneity in the HPLC profiles, all the fatty acid-linked peptides showed similar characteristics in terms of both fatty acid and amino acid compositions. The significance of fatty acids linked to P0 protein is discussed.
The new-generation acetylcholinesterase inhibitor, donepezil, is useful in the treatment of mild-to-moderate Alzheimer’s disease. A 72-year-old male chronic hemodialysis patient was diagnosed as having moderate Alzheimer’s disease. We administered donepezil at 3 mg/day orally to the patient. After 1 month’s treatment, the patient improved to a controllable psychiatric condition and was discharged from the hospital. The 24-hour plasma concentration profile of donepezil following the 3-mg once-daily dose varied from 11.1 to 18.2 ng/ml. The through level of donepezil was reduced from 12.4 to 10.9 ng/ml over a 3-month period. We did not experience any episodes of drug toxicity or adverse effects in this chronic dialysis patient. Donepezil treatment might have a beneficial impact on patients with severe renal dysfunction.
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