Kazuo Tajiri

Role of lipid peroxidation in acetaminophen-induced hepatotoxicity: comparison with carbon tetrachloride.

The effect of acetaminophen on lipid peroxidation in vivo and in vitro was studied in rat liver and the data were compared with those with carbon tetrachloride. Carbon tetrachloride increased diene conjugates in vivo and thiobarbituric acid reactive substance production in vitro in the liver microsomal incubation. These changes were further enhanced by ethanol that has previously been shown to increase carbon tetrachloride-induced hepatotoxicity. On the other hand, acetaminophen did not increase diene conjugates in vivo and inhibited thiobarbituric acid reactive substance production in vitro. These effects were minimally affected by ethanol which has previously been shown to inhibit acetaminophen-induced hepatotoxicity. Thus, lipid peroxidation may play a minimal role in acetaminophen-induced hepatotoxicity in contrast with carbon tetrachloride-induced hepatotoxicity.

Choledochocele with obstructive jaundice: A case report and a review of the Japanese literature

A case of a 57-year-old farmer with a rare type of choledochal cyst (choledochocele; Alonso-Lejs type III) is described. The patient was admitted because of obstructive jaundice and acute biliary infection. Abdominal computed tomography scan showed a cystic lesion in the head of the pancreas, and endoscopic retrograde cholangiopancreatography disclosed cystic dilatation of the terminal portion of the common bile duct. It was suspected that the choledochocele could swell and compress the common bile duct, causing obstructive jaundice and acute cholangitis; therefore, it was surgically resected. We also reviewed 61 cases of choledochocele reported in Japan; the findings were similar to those reported in the English literature.

Increased renal susceptibility to gentamicin in the rat with obstructive jaundice : role of lipid peroxidation

To study whether renal susceptibility to nephrotoxic stimuli is increased in obstructive jaundice, the effect of gentamicin on the renal function in bile duct-ligated rats was investigated. Gentamicin (50 mg/kg/day, subcutaneously) or saline was given to bile duct-ligated rats or sham-operated rats for six days. Mortality in the bile duct-ligated group that received gentamicin was 64% whereas that in the other groups was 0%. In the bile duct-ligated group, although serum creatinine and blood urea nitrogen were minimally affected, focal granulovacuolar degeneration in the proximal tubule was observed, which was accompanied by an increase in renal malondialdehyde. Gentamicin significantly increased serum creatinine and blood urea nitrogen levels and caused marked degeneration in the proximal tubule in the bile duct-ligated group, which was accompanied by a further increase in renal malondialdehyde, while these changes were not observed in the sham group. The kidney in obstructive jaundice appears to be susceptible to gentamicin. Enhanced production of oxygen radicals may be responsible for this effect.

Ischemic hepatitis in cirrhosis : Clinical features and prognostic implications

To characterize liver dysfunction in patients with cirrhosis after variceal bleeding, we analyzed 50 cirrhotic patients who had bleeding esophageal varices with or without shock. Increases in serum total bilirubin levels by 1.5 times were observed within 24 h in 11 of 12 patients with shock who died > 4 days after hemorrhage but in only one of eight patients with shock who survived (p < 0.01). Increases in serum aspartate aminotransferase and alanine aminotransferase by 2.5 times were observed in six patients in the former group but in none of the latter (p < 0.05). In postmortem livers, hepatocellular degeneration with minimal inflammatory cell infiltration was observed. Ischemic hepatitis is frequently noted in cirrhotic patients with ruptured esophageal varices. Patients with increases in the serum level of total bilirubin and/or aminotransferases within 24 h from onset of hemorrhage should be carefully treated even if hemorrhage is controlled.

Clinical Significance of Arterial Ketone Body Ratio in Chronic Liver Disease

Background: Arterial ketone body ratio (acetoacetate/3-hydroxybutyrate, AKBR) has been reported to be a useful tool for the estimation of liver functional reserve, but a more recent report has cast doubt on the clinical significance of this redox theory. Furthermore, the effect of a diminution of liver functional reserve on AKBR has not been documented in chronic liver disease. Methods: AKBR was measured in normal control subjects (n = 10), heavy alcohol drinkers (n = 19), patients with chronic hepatitis (n = 18) and patients with liver cirrhosis (n = 25). Results: Though AKBR was lower in heavy alcohol drinkers (1.66 ± 0.82) than in the other noncirrhotic groups (1.97 ± 0.93 in normal control subjects, 2.25 ± 1.11 in patients with chronic hepatitis), this discrepancy did not reach a level of significance. AKBR in patients with liver cirrhosis (1.18 ± 0.52) was significantly lower than that in normal controls (p < 0.01). AKBR in Child’s class A, Child’s class B, and Child’s class C was 1.20 ± 0.60, 1.07 ± 0.56, and 1.27 ± 0.45, respectively, and there were no significant differences among them. Conclusion: AKBR may be parallel to liver mitochondrial redox potential and hepatic functional reserve to some extent, but it does not appear to be an accurate parameter for their estimation.

Choledochal cyst with adenocarcinoma in the cystically dilated intrahepatic bile duct.

Abstract. A rare case of choledochal cyst complicated by papillary adenocarcinoma in the cystically dilated intrahepatic bile duct is reported. The tumor was located in the neck of the cystic lesion, and imaging modalities failed to show communication between the cystic lesion and the bile ducts.

Effects of caffeine on paracetamol activation in rat and mouse liver microsomes

1. The effects of caffeine on the NADPH-dependent production of paracetamol-glutathione conjugate were studied in rat and mouse liver microsomes. 2. In the presence of caffeine, glutathione conjugate production in rat microsomes was enhanced, whereas that in mouse microsomes was not affected significantly, showing an apparent species difference. 3. The data partly explain the species difference in the effects of caffeine on paracetamol hepatotoxicity.

Prompt treatment with peroral N-acetylcysteine for acute yellow phosphorus-induced liver injury: A rescued case report.

致死量をこえる黄リンを服用し, 肝機能障害とビタミンK不応性の凝固障害をきたしながら, N-acetylcysteine (以下NAC) の早期経口投与により救命しえた1例を経験した. 症例は56歳, 女性. 自殺目的にて“猫イラズ”1/2本以上 (黄リン800mg相当以上) をジュースに溶解し服用約2時間後, 嘔吐を主訴に受診した. 服薬状況より致死的と判断し, 同意を得たうえで服用9時間30分後にNACを胃管より投与した. 投与量は急性アセトアミノフェン中毒に準じた. 凝固因子はビタミンK投与にかかわらず, 第4病日にはPT43%, トロンボテスト18%まで低下した. GPTは第5病日に 191IU/lとピークに達したが, 黄疸は認めなかった. 回復期の肝生検では, 肝細胞内のリポフスチンの増加やクッパー細胞の腫大等を認め, 電顕上はrERの減少を認めた. 抗酸化剤のNACには内因性NOの産生・活性化作用が知られており, 黄リンによる急性肝不全を軽減しうる可能性が示唆された.

Ofloxacin prevents spontaneous bacterial peritonitis recurrence in HCV-antibody positive cirrhosis. A case report.

症例は66歳,男性.1982年に食道静脈瘤破裂で当科に入院し,内視鏡的硬化術を施行.その後もC型肝硬変に伴う肝性脳症や腹水のため入退院を繰り返していた.1992年3月と5月に特発性細菌性腹膜炎(SBP)にて入院.1回紹は腹水細菌培養陰性でCZXとDKBにて軽快した.2回目は黄色ブドウ球菌陽性でcefotaximeで軽快せずIMP/CSにて軽快した.同年6月にSBPが再発し入院.腹水中の好中球12,000/μlで細菌培養は陰性だった.IMP/CS長期投与にて7月末には軽快したが,8月初めに再発した.PIPCとCAZの投与で同年9月中旬には軽快した.以後再発を防ぐ目的でofloxacinの長期投与を開始したところ,1年9カ月後の今日までSBPの再発はみられていない.C型肝硬変に伴う再発性のSBPに対するofloxacinの有用性が示唆された.