Search

Hemorrhage arising from the coronary sinus is very rare and can be lethal. It has historically been treated surgically. The present patient had coronary sinus rupture secondary to esophageal cancer and an abscess in the pericardium. Due to her poor general status, this patient was contraindicated for surgery and underwent endovascular therapy. The hemorrhage was treated by stent graft deployment and the patient was temporarily discharged. Two months later, CT showed that the stent graft was occluded by thrombosis. The patient died without hemorrhage 2.5 months thereafter.

We examined how oxidative stress and cell damage develop in the liver of rats subjected to water-immersion stress (WIRS). In rats subjected to WIRS for 1.5, 3 or 6 h, serum alanine aminotransferase and aspartate aminotransferase activities increased time-dependently. In the liver tissue, vacuolization and apoptosis occurred at 1.5 h of WIRS and vacuolization further developed without further appearance of apoptosis at 3 h or 6 h. Serum lipid peroxide (LPO) and NOx (nitrite/nitrate) concentrations increased at 3 h of WIRS and these increases were enhanced at 6 h. In liver tissue, increases in LPO and NOx concentrations and myeloperoxidase activity and decreases in ascorbic acid and reduced glutathione concentrations and superoxide dismutase activity occurred at 3 h of WIRS and these changes were enhanced at 6 h, although vitamin E concentration and xanthine oxidase activity were unchanged. These results indicate that oxidative stress in the liver of rats with WIRS develops after the appearance of cell damage in the tissue, and suggests that oxidative stress is caused through disruption of the antioxidant defense system and increases in NO generation and neutrophil infiltration in the liver, which may contribute to the progression of cell damage in the tissue.

We examined whether xanthine oxidase (XO)-derived reactive oxygen species (ROS) contribute to the development of D-galactosamine (D-GaIN)-induced liver injury in rats. In rats treated with D-GaIN (500 mg/kg), liver injury appeared 6 h after treatment and developed until 24 h. Hepatic XO and myeloperoxidase activities increased 12 and 6 h, respectively, after D-GalN treatment and continued to increase until 24 h. D-GalN-treated rats had increased hepatic lipid peroxide (LPO) content and decreased hepatic reduced glutathione (GSH) and ascorbic acid contents and superoxide dismutase (SOD), catalase and Se-glutathione peroxidase (Se-GSHpx) activities at 24 h, but not 6 h, after treatment. Allopurinol (10, 25 or 50 mg/kg) administered at 6 h after D-GalN treatment attenuated not only the advanced liver injury and increased hepatic XO activity but also all other changes observed at 24 h after the treatment dose-dependently. These results suggest that XO-derived ROS contribute to the development of D-GaIN-induced liver injury in rats.

It is known that o-, m- and p-cresols exert a toxic effect on rat liver cells. However, there is little information on the mechanism for the hepatotoxicity of cresols. We, therefore, investigated the effects of o-, m-, and p-cresols on the bioenergetic system using isolated rat liver mitochondria. When o-, m- or p-cresol was added to liver mitochondria with glutamate or succinate at concentrations of 0.3 to 6.0 mumol/mg protein, each cresol isomer reduced the rate of state 3 respiration dose-dependently. Three cresol isomers at 6.0 mumol/mg protein each inhibited state 3 respiration in liver mitochondria with glutamate or succinate by about 60 or 20%, respectively. The three isomers affected NAD- and succinate-linked respirations in liver mitochondria, by which the respiratory control ratio was dose-dependently attenuated. The inhibitory effects of o-, m- and p-cresols on the NAD-linked respiration were stronger than those on the succinate-linked respiration. However, three cresol isomers had little effect on the P/O ratio in liver mitochondria with glutamate or succinate. Three cresol isomers at 15 mumol/mg protein each induced the swelling in the absence of Ca2+ in medium and accelerated the swelling of liver mitochondria in the presence of Ca2+ in medium. These results indicate that o-, m- and p-cresols inhibit liver mitochondrial respiration and induce or accelerate the swelling of liver mitochondria, and suggest that liver mitochondria may be one of the targets for the hepatotoxic actions of cresols.

The protective effects of betamipron (BP, N-benzoyl-beta-alanine) against nephrotoxicity induced by repeated cisplatin injections were examined. The ratio of the kidney weight to body weight and the lipid peroxide level after treatment with cisplatin plus BP tended to be larger and lower than those after treatment with cisplatin plus alkaline solution, respectively. The blood urea nitrogen, serum creatinine and glutathione levels in the animals treated with cisplatin plus BP differed significantly from those in the animals treated with cisplatin plus alkaline solution. Furthermore, the mechanism of the preventive effects of BP was analyzed for cisplatin-induced nephrotoxicity. The concentration of cisplatin in the renal cortex significantly decreased with concomitant BP. BP inhibited the uptake of cisplatin into the renal cortex in a competitive manner in the same way as an anionic transport inhibitor, probenecid. The treatment with BP appears to be useful for the renal toxicity induced by repeated cisplatin administration.

Prophylactic effects of N-benzoyl-beta-alanine (betamipron, BP), one of a series of N-acyl amino acids, were examined against cisplatin-induced nephrotoxicity. Male Wistar rats were injected i.p. with 6 mg/kg of cisplatin combined with an i.p. BP dose given at various times and various doses. Rats were sacrificed 5 days after cisplatin injection to weigh the kidney and liver, and to determine blood urea nitrogen (BUN) and serum creatinine (serum Cr) levels. Preliminary results suggest that treatment with BP is an effective means of protection against cisplatin-induced nephrotoxicity. Combination with BP reduced the weight loss following treatment with cisplatin. The ratios of the kidney and liver weights to the body weight in the animals treated with cisplatin followed later with BP are significantly different (p0.05) from those in the animals that received only cisplatin. The BUN and serum Cr levels in the animals treated with cisplatin followed from -1 to 4 hr, and from -4 to 4 hr later with 250 mg/kg BP dose and followed 1 hr later with from 250 to 1000 mg/kg, and from 250 to 2000 mg/kg BP doses differed significantly (p0.05) from those in the animals that received only cisplatin. Histological analysis of the kidneys confirmed the protective effect of BP.