|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1996 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥700,000 (Direct Cost : ¥700,000)
1) Clinical study
Indirect calorimetry was performed at resting and at 1 hour after infusion of branched-chain amino acid (BCAA) solution (83.6g total amino acids/L,Fischer's ratio 37.1,500ml for 2hr) in 12 patients with fulminant hepatitis (FH), 12 patients with severe type of acute hepatitis (AHS), and 8 healthy controls (HC). Energy expenditure (Kcal/day and a ratio standardized to the estimated basal metabolic rate ; EE/BMR) and oxidation volumes of carbohydrate, fat and protein (g/day) were measured. EE/BMR was significantly higher in patients with FH and in those with AHS than in HC.Infusion of BCAA significantly raised EE/BMR in moderately metabolic FH,in AHS and in HC,although it did not affect the index in hypermetabolic FH.Increases in the protein oxidation volume were brought by BCAA infusion in moderately metabolic FH,in AHS and in HC but not in hypermetabolic FH.In conclusion, BCAA can be utilized as an energy substrate in patients with AHS and in cases of FH with moderatel
y metabolic state. Precise analysis of energy metabolism is essential in advance, with a use of BCAA infusion in patients with AHF.
2) Experimental study
AHF was induced in male Donryu rats by giving lypopolysaccaride intravenously and D-galactosamine hydrochloride intraperitoneally. From 18 hours after injection, AHF and control rats were given one of the following five solutions intravenously for 6 hours : 1) saline, 2) 10% glucose, 3) standard 10% amino acid formula with total nitrogen content of 12.2g/L and BCAA/aromatic amino acid molar ratio of 37.05,4) BCAA-enriched solution with nitrogen content of 21.9g/L and the ratio of 148.2, or 5) an active placebo against BCAA-enriched solution with nitrogen content of 21.9g/L and the ratio of 37.05. In parallel, each group was given a continuous infusion of ^<14>C-leucine, protein turnover was analyzed according to the kinetic model. When compared with the control, rates of total protein turnover (total flux), oxidation and breakdown all increased significantly in AHF.Infusion of standard 10% amino acid formula, BCAA-enriched solution or the placebo in AHF increased total flux and oxidation significantly as compared with the effect of saline or 10% glucose. Although saline, 10% glucose, standard 10% amino acid formula, and the placebo had no effect on synthesis rate, it was increased significantly with BCAA-enriched solution. Breakdown was not suppressed with any solutions. These results suggest that rats with AHF are in a catebolic state and that any of the three amino acid solutions can be oxidized to provide energy in AHF.In addition, infusion of BCAA-enriched solution may have a specific protein-sparing effect by increasing the protein synthesis.
AHFラットでは対照群に比してLeuのbreakdownおよびoxidationはいずれも有意に亢進しており、蛋白異化亢進状態が存在した。このモデルに標準のF液(総窒素量12.2g/L, F比37.05)を投与すると、Leuのoxidationは有意に増加していることから、投与されたBCAAは代謝されているものと考えられた。さらにBCAAを豊富に含む輸液(総窒素量21.9g/L, F比148.2)およびactive placebo輸液(総窒素量21.9g/L, F比37.05)投与後の代謝動態についても検討すると、BCAAを豊富に含む輸液ではsynthesisの増加(protein-sparing effect)が観察された。しかしながら急性肝不全において亢進しているbreak downの抑制作用は、いずれの輸液においても認められなかった。 Less