Takahiro Obata

Characteristic change in serum amino acid levels in different types of hepatic encephalopathy

SummarySerum amino acid patterns in patients with different types of hepatic encephalopathy were investigated. Marked elevations in most of serum amino acids observed in untreated patients with acute type of fulminant hepatitis were not remarkable in the patients who have already treated; particularly branched chain amino acids (BCAA), phenylalanine and tyrosine were much lower in the latter group. However, elevation of serum methionine levels and lower ratio of BCAA/(phenylalanine + tyrosine) were similarly observed in both groups. In encephalopathic patients with decompensated cirrhosis, many amino acids such as phenylalanine, tyrosine and methionine were elevated with a slight depressed levels of serum BCAA. Highly significant decrease in serum BCAA levels and no elevation of phenylalanine and methionine with a minimal increase of typosine were observed in patients with chronic type of hepatic encephalopathy; other amino acids except for glutamine and arginine were much lower as compared to those in decompensated cirrhotics and even to the control values.

Intrahepatic cholestasis and hyperbilirubinemia in ethynyl estradiol and chlorpromazine-treated rats

SummaryIntrahepatic cholestasis associated with hyperbilirubinemia was induced by the simultaneous administration of ethynyl estradiol (EE) and chlorpromazine hydrochloride (CPZ) for 7 days to female Sprague-Dawley rats. Increases in direct serum bilirubin levels and alkaline phosphatase activities were observed concomitantly with diminished bile flow and bile acid excretion. However, the bilirubin output in the bile remained unchanged. [14C]Erythritol clearance decreased in parallel with the diminished bile flow, while [14C]sucrose biliary clearance increased, suggesting that the decrease in bile flow was of canalicular origin and also due to increased permeability in the biliary tract. There was a prominent decrease in the bile acid-independent flow, and the bile acid-dependent flow also decreased concomitantly with the diminished bile acid excretion. Slight increases in cytochrome P-450 and anilin hydroxylase activities in liver microsomes were observed, and bilirubin UDP-glucuronyl transferase activity increased significantly. Indirect bilirubin clearances determined by a bilirubin load test were markedly reduced in the icteric rats. The bilirubin load test also suggested that bilirubin flowed back into the circulating blood and that gluculonidation of bilirubin mono-gluculonide (BMG) to bilirubin diglucuronide (BDG) was impaired. Light microscopic examinations of the liver revealed marked proliferation of the bile ductules and numerous vacuoles in the hepatocytes. Dilatation of the bile canaliculi with diminished microvilli was also detected by scanning electron microscopy.

Effects of intraduodenal feeding of a branched-chain amino acid-rich solution on ammonia-induced encephalopathy in liver-injured rats

SummaryA preventive effect of intraduodenal prefeeding of a branched-chain amino acid (BCAA)-rich solution on ammonia-induced encephalopathy was investigated with carbon tetrachloride (CCl4)-injured rats with the elevated levels of blood ammonia. Five out of six cirrhotic rats, to which an electrolyte solution alone was preinfused for 24 hours, fell into coma following ammonia acetate injection and two comatose rats died. However, no cirrhotic rats preinfused with a BCAA-rich solution died and only two out of the six showed coma with complete recovery. The similar preventive effect could not be observed in rats with acute liver injury.

Brain tyrosine hydroxylase activity and calculated amount of brain dopa synthesized in carbon tetrachlorideintoxicated rats

SummaryTyrosine hydroxylase activity in the corpus striatum was measured in a large dose of carbon tetrachloride (CCl4)-intoxicated rats in order to confirm whether brain catecholamine contents decrease in acute hepatic failure or not. Theoretical amounts of dopa synthesized in the brain of the treated animals were calculated according to an equation of enzyme kinetics. Tyrosine hydroxylase activities in CCl4-injured rats were similar to those in control rats, and calculated amounts of brain dopa in liver-injured rats were rather higher as compared to those in untreated animals.

Serum alpha-fetoprotein levels following cessation of alcohol in medical and psychiatric subjects with long-term excess drinking.

Serum alpha-fetoprotein (AFP) concentrations were serially determined during the period following cessation of alcohol on thirty-five medical and psychiatric patients with histories of long-term excess drinking. In all except two cirrhotics with posttransfusion hepatitis and hepatocellular carcinoma, all AFP determinations for more than 2 months following abstinencewere negative(