Hepatitis: Yagi K

Yagi K, Kojima M, Oyagi S, Ikeda E, Hirose M, Isoda K, Kawase M, Kondoh M, Ohgushi H. · Graduate School of Pharmaceutical Sciences, Osaka University, Suita City, Japan. · Yakugaku Zasshi. · Pubmed #18176050 links to  free full text

Abstract: Stem cell-based therapy has received attention as a possible alternative to organ transplantation, owing to the ability of stem cells to repopulate and differentiate at the engrafted site. We transplanted bone marrow-derived mesenchymal stem cells (BMSCs) into liver-injured rats to test the therapeutic effect. Rat bone marrow cells were cultured in the presence of hepatocyte growth factor (HGF). RT-PCR and immunocytochemical analysis indicated that the BMSCs expressed the albumin mRNA and the production of protein after cultivation with HGF for 2 weeks. The BMSCs appeared to differentiate into hepatocyte-like cells in response to the culture with HGF. After labeling with a fluorescent marker, the BMSCs were transplanted into CCl(4)-injured rats by injection through the caudal vein. The liver was excised and blood samples were collected 4 weeks later. Engraftment of the transplanted BMSCs was seen with significant fluorescence in the injured liver. Transplantation of the BMSCs into liver-injured rats restored their serum albumin level and suppressed transaminase activity and liver fibrosis. Therefore, BMSCs were shown to have a therapeutic effect on liver injury. Recently, we have been trying to use mesenchymal stem cells isolated from dental papilla of discarded human wisdom teeth. Autologous transplantation of mesenchymal stem cells from bone marrow and dental papilla could be ethically and functionally promising for stem cell-based therapy.

Mugishima H, Matsunaga T, Yagi K, Asami K, Mimaya J, Suita S, Kishimoto T, Sawada T, Tsuchida Y, Kaneko M. · Study Group of Japan for Treatment of Advanced Neuroblastoma, Gunma. · J Pediatr Hematol Oncol. · Pubmed #11990713 No free full text.

Abstract: PURPOSE: To determine the dose-limiting toxicity, maximum tolerated dose, and potential efficacy of irinotecan in children with refractory malignant solid tumors. PATIENTS AND METHODS: In the present phase I clinical trial, 28 patients received irinotecan 50 to 200 mg/m2 per day by intravenous 2-hour infusion over the course of 3 days, repeated once after an interval of 25 days. Fifty-one treatment courses were administered to these patients. RESULTS: Dose-limiting toxicities were observed at the dose of 200 mg/m2 per day for 3 days. Diarrhea and hematopoietic toxicities were the dose-limiting factors, and the former required support with intravenous fluid administration. The occurrence of vomiting was variable. Decreases in clinical tumor marker levels were observed in the majority of patients who received two cycles of irinotecan 80 mg/m2 per day to 200 mg/m2 per day over the course of 3 days, and partial response was attained in four patients who received irinotecan in two cycles of 140 mg/m2 per day to 200 mg/m2 per day over the course of 3 days. Pharmacokinetic studies showed that the plasma concentration of irinotecan and its active metabolite SN-38 ranged from 93 to 2,820 ng/mL and 5.2 to 34.8 ng/mL, respectively, during 3-day infusions of irinotecan 200 mg/m2 per day. The mean clearance of irinotecan was 14.54 L/h per m2 (range 8.45-20.83 L/h per m2). CONCLUSION: The maximum tolerated dose was determined to be a dose of irinotecan between 160 mg/m2 per day and 180 mg/m2 per day administered over the course of 3 consecutive days on an inpatient basis, repeated once after 25 days off, and our results indicate that irinotecan is a promising anticancer agent that is worthy of phase II trials in pediatric solid tumors.

Isoda K, Kagaya N, Akamatsu S, Hayashi S, Tamesada M, Watanabe A, Kobayashi M, Tagawa Y, Kondoh M, Kawase M, Yagi K. · Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan. · Biol Pharm Bull. · Pubmed #18239293 links to  free full text

Abstract: Vitamin B(12) contains a cobalt complex and accumulates at high levels in the liver. Vitamin B(12) was examined for its hepatoprotective effect on dimethylnitrosamine-induced liver injury in mice. Vitamin B(12) decreased the blood levels of aspartate aminotransferase and alanine aminotransferase, and clearly inhibited the overaccumulation of collagen fibrils. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the liver showed that the gene expression of alpha-smooth muscle actin and heat-shock protein 47, which are markers of fibrosis, were suppressed by vitamin B(12) administration. Our findings indicate that vitamin B(12) could be an effective hepatoprotective agent.

Zenda T, Murase Y, Yoshida I, Muramoto H, Okada T, Yagi K. · Department of Internal Medicine, Kanazawa Social Insurance Hospital, Japan. · Eur J Gastroenterol Hepatol. · Pubmed #12702914 No free full text.

Abstract: A 68-year-old female with mild diabetes mellitus was admitted because of acute liver dysfunction due to autoimmune hepatitis. While 40 mg/day of prednisolone improved hepatic dysfunction dramatically, her diabetic milieu deteriorated seriously. The induced hyperglycaemia could not be controlled sufficiently, despite a high dose of insulin (> 110 units/day), suggesting the existence of insulin insensitivity and hyperinsulinaemia. Soon after introduction of insulin therapy, she developed severe anasarca, including marked peripheral oedema, ascites and pleural effusion. Anasarca eventually subsided within 4 weeks with the use of a diuretic agent. We conjectured that the side effects of insulin, such as anti-natriuresis and increased vascular permeability, might be pronounced in the presence of the hepatic dysfunction that accompanies insulin insensitivity, hyperinsulinaemia and hypoalbuminaemia.

Ueki Y, Isozaki E, Miyazaki Y, Koide R, Shimizu T, Yagi K, Hirai S. · Department of Neurology, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan. · Acta Neurol Scand. · Pubmed #12100372 No free full text.

Abstract: We report two patients with chronic acquired hepatocerebral degeneration (CAHD) who showed neurological and radiological improvement after the administration of branched-chain amino acids (BAA). The first patient with chronic hepatitis C presented with progressive parkinsonism for 7 months, whereas the second patient with liver cirrhosis presented with progressive ataxia for 15 months. T1-weighted magnetic resonance imaging (MRI) showed symmetric high intensity signals in the lenticular nuclei in both patients. In the first patient, single photon emission computed tomography (SPECT) disclosed a marked decrease in cerebral blood flow in the parieto-occipital regions. In the second patient, T2-weighted MRI demonstrated symmetric high intensity signals in the deep cerebral and cerebellar white matter. After the administration of BAA, their neurological signs and radiological abnormalities markedly improved in both patients. CAHD might be a reversible and treatable disorder where aromatic amino acids are deeply involved in its pathogenesis.