[Prognostic judgment of fulminant hepatitis by measurement of hepatosplenic volume ratio by computed tomography].

The liver and spleen volume ratio (S/L ratio) was estimated with X-ray computed tomography and evaluated by comparison with the prognosis in 10 patients with fulminant hepatitis. S/L ratio of control group (n = 10) was 0.122 +/- 0.026 (mean +/- SD), that of the alive group with fulminant hepatitis (n = 5) was 0.112 +/- 0.021, and that of the dead group (n = 5) was 0.308 +/- 0.136. There is a significant difference between S/L ratio of control group and that of the dead group with fulminant hepatitis. The rise of S/L ratio on the patients with fulminant hepatitis reflects the liver atrophy or splenomegaly and the prognosis was poor. The prognosis of the patients with fulminant hepatitis, whose S/L ratio indicated the near value of control group, was good. The measurement of S/L ratio by computed tomography was considered to be useful to evaluate the prognosis of fulminant hepatitis.

Lipopolysaccharide-mediated hepatic glutathione depletion and progressive mitochondrial damage in mice: protective effect of glutathione monoethyl ester.

Overproduction of reactive oxygen intermediates (ROI) may have an important role in the pathophysiology of lipopolysaccharide-mediated liver-injury. This study examined the role of cytosolic and mitochondrial glutathione in protecting hepatocytes from oxidative stress during exposure to lipopolysaccharide. In addition, the possible participation of changes of inner mitochondrial membrane permeability in lipopolysaccharide-induced hepatotoxicity was investigated. The changes of hepatic glutathione content following lipopolysaccharide challenge (2 mg/kg) were measured in mice by reverse-phase high-performance liquid chromatography. Glutathione depletion and a glutathione-rich state were produced by intraperitoneal administration of a specific inhibitor of gamma-glutamyl cysteine synthetase, buthionine sulfoximine (3 mmol/kg), and by administration of glutathione monoethyl ester (10 mmol/kg), respectively. Intracellular ROI generation and the mitochondrial membrane potential were quantified by flow cytometry. Changes of inner mitochondrial membrane permeability in hepatocytes were assessed by radioactive sucrose entrapment. There was increased production of ROI along with depletion of cellular and mitochondrial glutathione in the liver after lipopolysaccharide administration. There was also a change of inner mitochondrial membrane permeability in hepatocytes, with the loss of coupled functions. Buthionine sulfoximine decreased the hepatic antioxidant capacity, worsened mitochondrial function, and reduced the survival rate of the mice. In contrast, glutathione monoethyl ester improved all of these parameters. Glutathione may have an important role in cellular defenses against lipopolysaccharide-induced liver damage in mice, and excessive oxidative stress may precipitate the mitochondrial membrane permeability transition in hepatocytes and lead to cell death.

Assessing the eligibility for liver transplantation of patients with fulminant hepatitis.

The spleen to liver volume (S/L) ratio of 13 patients with fulminant hepatitis was determined using X-ray computed tomography (CT), and the correlation between S/L ratio and prognosis was evaluated. The S/L ratio of 6 patients who died was greater than 0.16, whereas that of the remaining 7 patients who survived was less than 0.15. These findings suggest that determining the S/L ratio using CT may be useful for assessing the eligibility of patients with fulminant hepatitis for liver transplantation.

Hyperammonemia reduces water immersion--restraint stress gastric ulcers in rats.

1. The influence of hyperammonemia (produced by the continuous intraperitoneal infusion of ammonium acetate for 6 days) on stress-induced gastric ulcer formation was investigated in conscious rats. 2. Continuous ammonium acetate infusion significantly reduced stress-induced gastric ulceration concomitant with an increase in gastric blood flow, as determined using radioactive microspheres. The serum levels of L-arginine as well as nitrite and nitrate (oxidative byproducts of nitric oxide) were increased by ammonium acetate infusion. 3. Prior administration of N omega-nitro-L-arginine methyl ester, a competitive nitric oxide synthase inhibitor, substantially attenuated the increase in gastric blood flow caused by ammonium acetate infusion and diminished the protective effect on gastric ulceration. 4. These findings suggest that the synthesis of endogenous nitric oxide from L-arginine is accelerated by continuous ammonium acetate infusion when the urea cycle remains intact and has a substantial cytoprotective effect on the stomach, probably through maintaining the gastric mucosal microcirculation.

Hypoxia alters the energy metabolism and aggregation of washed human platelets.

Washed human platelets were incubated under hypoxic and normoxic conditions to investigate the influence of oxygen deprivation on energy metabolism and aggregation. The maximum aggregation rate, oxygen consumption, lactate production, and adenine nucleotide content were measured. Hypoxic incubation decreased the oxygen burst and maximum aggregation induced by thrombin, and accelerated anaerobic glycolysis. ATP and ADP levels were preserved, but the hypoxanthine level increased in the incubation medium and the platelet AMP level and adenylate energy charge decreased compared with normoxic incubation. Thus, anaerobic glycolysis failed to compensate for impaired oxidative phosphorylation during hypoxic incubation, suggesting that oxidative energy is essential for full platelet function.

Activation of neutrophil function by recombinant human granulocyte colony-stimulating factor improves the survival of rats with peritonitis.

We examined the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and cefmetazole sodium on survival, neutrophil count, and neutrophil function in rats with peritonitis produced by cecal ligation and puncture. Rats with peritonitis received either rhG-CSF (50 or 100 micrograms/kg) with or without cefmetazole (50 mg/kg) for 3 days, cefmetazole alone, or no treatment and were evaluated as controls. The mortality rate of all treated rats was significantly lower than that of the untreated rats. The survival rate was 57.1% for the rats given both rhG-CSF and cefmetazole, but there was no significant improvement of survival as compared with cefmetazole therapy alone. Treatment with rhG-CSF at 100 micrograms/kg caused the circulating neutrophil count to increase significantly. The phagocytic activity for latex beads and neutrophil H2O2 production showed a greater enhancement by phorbol myristate acetate (PMA) in the untreated rats, thus indicating that neutrophils from treated rats were more activated. These findings show that rhG-CSF can improve survival and neutrophil function in rats with peritonitis, while combined therapy with cefmetazole was also found to be beneficial.

DNA damage induced by tumour necrosis factor-alpha in L929 cells is mediated by mitochondrial oxygen radical formation.

Treatment of L929 cells with tumour necrosis factor-alpha (TNF-alpha) plus actinomycin D induced DNA damage (indicated by the appearance of a sub-G1 peak due to extracellular leakage of low molecular weight DNA following DNA fragmentation) before significant cell lysis occurred. The DNA damage occurred in parallel with a decrease of the intracellular total glutathione content and an increase of intracellular reactive oxygen intermediates (ROI), as indicated by increased dihydrorhodamine 123 oxidation. Because the inhibition of mitochondrial respiration suppressed the increase of dihydrorhodamine 123 oxidation and DNA damage as well as the decrease in the total glutathione content, it was suggested that increased mitochondrial formation of ROI was responsible for DNA damage after TNF treatment. Deferoxamine (a ferric iron chelator) and dithiothreitol (a sulfhydryl reagent) both prevented DNA damage and cell killing, indicate that hydroxyl radicals generated from O2- and H2O2 produced by the mitochondria in a process catalysed by iron contributed to DNA damage and that this pathway may be involved in TNF-alpha-induced cytotoxicity. An inhibitor of poly(ADP)-ribose polymerase (3-aminobenzamide), worsened DNA damage, but was protective against cell lysis, suggesting that DNA repair subsequent to injury was more important than DNA damage per se in development of TNF-alpha cytotoxicity.

Malignant hemangioendothelioma of the small intestine: report of a case.

A case of malignant hemangioendothelioma (MH) of the small intestine in a 27-year-old woman is reported herein. The patient developed acute abdominal symptoms during investigations for anemia, weight loss, anorexia, and recurrent gastrointestinal bleeding. An emergency laparotomy revealed perforation of a jejunal tumor. The results of a histopathological study of the resected small bowel segment were interpreted as MH with lymph node involvement. Following this case report, a review of the relevant literature on small intestinal MH is presented.

A solitary fibrous tumor in the perianal region with a 13-year follow-up: report of a case.

A case of a solitary fibrous tumor (SFT) of the perianal region in a 62-year-old man is reported herein. The patient had undergone an abdominoperineal excision of the rectum for an anorectal tumor 13 years previously, and had been referred to our hospital for a perineal mass. Computerized tomography and angiography revealed a markedly hypervascular tumor measuring 11 x 8 cm in size in the pelvic cavity. After preoperative radiotherapy (total 58 Gy) and the embolization of the feeding arteries, he underwent an en bloc excision of the tumor. Microscopically, the tumor was composed of spindle shaped cells with a "patternless" arrangement in a collagenous background. There was immunohistochemical evidence that these cells were strongly positive for CD34, thus suggesting the tumor to be SFT. The previously resected anorectal tumor showed similar histological and immunohistochemical findings. The patient's recovery was uneventful.