Insulin-like growth factor-I prevents lethal acute liver failure induced by D-galactosamine and lipopolysaccharide in rats

The aim of this study was to evaluate the effect of insulin-like growth factor-I (IGF-I) on lethality and liver function in experimental acute liver failure. Intravenous co-administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) to rats induced high mortality and marked increases in aspartate aminotransferase, alanine aminotransferase and total bilirubin, associated with hypoglycemia. One-hour pre-treatment with IGF-I significantly prevented lethality and blood parameter changes in rats. Histological examination also showed that massive hepatocellular hemorrhagic necrosis and inflammatory cell infiltration around peri-central veins in the liver, as well as shrinkage of cytoplasm and nuclear condensation, were induced by GalN plus LPS injection, but these all were improved by pre-treatment with IGF-I. Overall, this study showed that IGF-I treatment resulted in effective prevention of lethal acute liver failure in rats induced by GalN plus LPS, suggesting a therapeutic potential for IGF-I in the prevention of acute liver failure.     

New method of catheter-port system implantation in hepatic arterial infusion chemotherapy

BACKGROUND: This report describes a novel method of implantation of the catheter-port system in hepatic arterial infusion chemotherapy, which is the inferior epigastric arterial approach. METHODS: Using this method, the length of incision is about 3 cm in lower abdomen. The inferior epigastric artery is exposed above the inguinal ligament. The half of the artery is cut, and a vascular sheath is inserted into the external iliac artery along a guide wire. A catheter is inserted into the hepatic artery through the vascular sheath. Coil occlusion of nontarget artery is performed by the technique of interventional radiology. Then the vascular sheath is removed and the catheter is fixed to the inferior epigastric artery. A port is connected to the catheter and placed above the incision in the lower abdomen. CONCLUSIONS: Using this method, the hip joint can be moved freely and port-related complications are few, which contributes to a good quality of life of patients during the therapy. The inferior epigastric arterial approach may give a benefit to those who are treated with hepatic arterial infusion chemotherapy.     

Comparison of hepatotoxicity and metabolism of butyltin compounds in the liver of mice,rats and guinea pigs

The hepatotoxicity of tributyltin chloride (TBTC) and dibutyltin dichloride (DBTC) was compared among mice, rats and guinea pigs in vivo. Further, the metabolism of these butyltin compounds in the liver was also investigated in these species. The oral administration of TBTC and DBTC to mice induced obvious liver injury, as demonstrated by both serodiagnosis and histopathological diagnosis. The concentrations of TBTC and DBTC that induced hepatotoxicity in mice at 24 h after oral administration were 180 and 60 micro mol/kg, respectively. In the case of rats, the liver injury induced by TBTC and DBTC was detected at 24 h by the serodiagnosis, but not by histopathological diagnosis. On the other hand, in guinea pigs, TBTC and DBTC administration did not produce any clear liver injury at 24 h, as evaluated by these two diagnostic methods. Thus, the following ranking was obtained with regard to increasing order of sensitivity to liver injury caused by TBTC and DBTC: mice, rats and guinea pigs. The total butyltin contents in the liver of mice were equivalent at 3 h and 24 h after the administration of TBTC or DBTC; however, the contents in the liver of rats and guinea pigs were relatively lower at 3 h and higher at 24 h than those of mice, although there were no differences between rats and guinea pigs in the total liver butyltin content. Concerning the liver metabolism of these butyltin compounds, the main form of butyltin compounds in these animals treated with TBTC was DBTC within 3 h after oral administration, while the main metabolites at 24 h were different in each species, indicating that the liver metabolism of TBTC might vary by animal type. When the animals were treated with DBTC orally, DBTC was hardly metabolized in the livers of these animals even at 24 h, and the liver levels of DBTC were two times greater in mice and guinea pigs than in rats at 3 h and were lower in mice at 24 h than in rats and guinea pigs. The analysis of cellular distributions of DBTC in the liver at 3 h after the administration showed that the levels of DBTC in the nuclear, microsomal and mitochondrial fractions of mice hepatocytes were relatively higher than in those of rats, which were greater than in those of guinea pigs. These results suggest differences in the sensitivity of mice, rats and guinea pigs to hepatotoxicity caused by butyltin compounds and demonstrate that the difference in the sensitivity of these animals to the hepatotoxicity induced by TBTC and DBTC may be partly due to differences in hepatic metabolism of TBTC and in the distribution of DBTC within cell organelles, respectively.     

Analysis of the p53 gene in parotid gland cancers: a relatively high frequency of mutations in low-grade mucoepidermoid carcinomas

Mutations and overexpression of the p53 gene and protein were analyzed in 40 cases with various types of parotid gland cancers. Mutations were found in 12 cases (30%), and low-grade mucoepidermoid carcinomas (43%) and highly malignant carcinomas including adenocarcinoma, salivary duct carcinoma, and undifferentiated carcinoma (56%) showed a relatively high frequency of mutations. Overexpression of the protein was observed in 11 cases (28%) and 4 of the 11 cases also had p53 mutations. These results suggest that mutations of the p53 gene have significance in certain types of parotid cancers irrespective of the aggressiveness of a tumor type.     

A case of intra-peritoneal recurrence of colon carcinoma that responded remarkably to combined therapy of low-dose leucovorin and 5-fluorouracil

We treated a patient with intra-peritoneal recurrent tumor from colon cancer who responded completely to chemotherapy of combined low-dose Leucovorin (LV) and 5-fluorouracil (5-FU). The patient was a 75-year-old man. He underwent resection of the transverse colon, sigmoid colon and distal stomach for colon and gastric cancers. Nine months after the operation, his CEA level increased to 39.5 ng/ml and a CT scan revealed an intra-peritoneal tumor measuring about 5 cm. He received chemotherapy of 30 mg/day of LV that was injected in a bolus and 500 mg/day of 5-FU that was given i.v. by continuous infusion for 10 days. At the end of 2 cycles of this regimen, CT scan demonstrated complete tumor remission and the patient's CEA level decreased to normal level. After an additional cycle of this regimen, he received modulated chemotherapy combined with l-Leucovorin and 5-FU as an outpatient. However, after 3 months of treatment, a recurrent tumor was detected in the same portion and the first regimen was re-started for 5 days. After 4 cycles of treatment the tumor disappeared completely from a CT scan. It is important to investigate effective regimens that do not reduce the quality of life of the patient. This clinical experience suggests that a low-dose LV/5-FU therapy may be beneficial to patients with recurrent colon cancer. Further investigation is necessary to establish an effective regimen that can be given for a long period without adverse effects on quality of life.     

Complications of the treatment of endoscopic biliary strictures developing after liver transplantation

Background

Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation (OLT). Endoscopic management by the conventional methods of biliary dilatation and/or stent placement has been successful, but sometimes severe complications occur, necessitating prolonged therapy. The aim of this study is to clarify the complications of the endoscopic approach for endoscopic dilatation and/or stent placement.

Method

Of 46 patients who underwent living-donor liver transplantation, 10 were diagnosed as having anatomic biliary strictures by endoscopic retrograde cholangiopancreatography (ERCP). Two patients developing biliary strictures after deceased-donor liver transplantation were also enrolled in the study. For the purpose of comparison, 302 patients with a total of 550 consecutive ERCP cases (including 115 patients with 250 malignant bile duct strictures) were recruited in this study. Success rate, number of endoscopy sessions, the median procedure time for ERCP, and incidence of complications including post-ERCP pancreatitis were compared in the OLT cases and other cases.

Results

The following results were obtained in the OLT cases, malignant stricture cases, and all cases, respectively: mean number of endoscopy sessions was 3.62, 2.17, and 1.94 (P?=?0.0216, P?P?=?0.0327, P?=?0.0093); and severe pancreatitis occurred in 2 cases of OLT. In a univariate analysis for post-ERCP pancreatitis, OLT was extracted as the only significant risk factor.

Conclusions

Endoscopic maneuvering for biliary dilatation and/or stent placement following OLT was associated with a higher risk of post-ERCP pancreatitis than the use of the same technique for the treatment of malignant biliary stricture. Endoscopic treatment after OLT was a significant risk factor for post-ERCP pancreatitis.     

Maturation of somatosensory evoked potentials upon posterior tibial nerve stimulation

Somatosensory evoked potentials produced in response to posterior tibial nerve stimulation were studied in 42 normal infants and children, ages 4 months to 16 years. The maturation of afferent conduction from the lower limb was evaluated for the peripheral nerve, spinal cord, and central nervous system. Although the maturation of conduction in the peripheral nerve (from the ankle to the popliteal fossa and from the popliteal fossa to L₃) was complete by 6 years of age, afferent conduction in the spinal cord (from L₃ to C₇) was not complete until 12 years of age or older. Spinal evoked potentials investigated in the thoracolumbar area revealed a phase-reversed potential located between the lower thoracic spine and upper lumbar spine in over 80% of patients. Reciprocal velocities for the major cortical positive potential P₁ (corresponding to P₃₇ in adults) and its onset, N₁, steadily decreased with age and leveled off at greater than 12 years of age and by 12 years of age, respectively. The propagation velocity from L₃ to the cerebral cortex also increased steadily with age, leveling off at greater than 12 years of age. Accordingly, the maturation of afferent conduction in the central nervous system was not complete until affer 12 years of age.     

Effect of physical training on the responses of serum adrenocorticotropic hormone during prolonged exhausting exercise

Summary The purpose of this study was to investigate the effects of physical training on the responses of serum adrenocorticotropic hormone (ACTH) and cortisol concentration during low-intensity prolonged exercise. Five subjects who had fasted for 12 h cycled at the same absolute intensity that elicited 50% of pre-training maximal oxygen uptake ( O_2max), either until exhaustion or for up to 3 h, before and after 7 weeks of vigorous physical training [mean daily energy consumption during training exercise, 531 kcal (2230 kJ)]. In the pre-training test, serum ACTH and cortisol concentrations did not increase during the early part of the exercise. Increases in concentrations of both hormones occurred in all subjects when blood glucose concentration decreased during the later phase of the exercise. The mean values and SEM of serum ACTH and cortisol concentrations at the end of the exercise were 356 ng · l^–1, SEM 79 and 438 g · l^–1, SEM 36, respectively. After the physical training, O_2max of the subjects improved significantly from the mean value of 50.2 ml · kg^–1 · min^–1, SEM 2.5 to 57.3 ml · kg^–1 · min^–1, SEM 2.0 (P < 0.05). In the post-training test, exercise time to exhaustion was prolonged in three subjects. Comparing the pre- and post training values observed after the same length of time that the subjects had exercised in the pre-training test, the post-training values of serum ACTH (44 ng · l^–1, SEM 3) and cortisol (167 g · l^–1, SEM 30) concentration were less than the pre-training value (P < 0.05). However, after the subjects stopped exercising in the post-training test, the serum ACTH (214 ng · l^–1, SEM 49) and cortisol (275 g · l^–1, SEM 50) concentrations were not significantly different from those measured after the subjects stopped exercising in the pre-training test (P > 0.10). In conclusion, high-intensity physical training reduced the responses of both hormones during prolonged exercise, propbably because of a delayed decrease of blood glucose concentration after physical training, while the level of the blood glucose concentration which induces ACTH and cortisol secretion did not change.     

Tacrolimus (FK506) limits accumulation of granulocytes and platelets and protects against brain damage after transient focal cerebral ischemia in rat

We investigated the neuroprotective effect of tacrolimus (FK506) on the ischemia-reperfusion injury caused by transient focal brain ischemia induced by middle cerebral artery (MCA) occlusion for 60 min in rats. Neuronal damage visualized as a decrease of MAP2 immunoreactivity was observed in the cerebral cortex at 9 h after MCA occlusion and further expanded at 24 h. Hypoxic areas visualized with an immunohistochemical reaction for 2-nitroimidazole, a hypoxia marker (hypoxyprobe-1), and accumulation of granulocytes and platelets were also observed at 9 h and 24 h after MCA occlusion. Tacrolimus (1 mg/kg, i.v.), administered immediately after MCA occlusion, attenuated cortical damage and decreased the hypoxyprobe-1 positive area, as well as the number of granulocytes and platelets at 24 h after MCA occlusion. Immunohistochemical analysis showed that tacrolimus reduced the number of blood vessels positively stained for ICAM-1, E-selectin and P-selection. These results suggested that tacrolimus limited attachment of granulocytes and platelets to blood vessels by inhibiting the expression of adhesion molecules and protected neuronal tissue from hypoxic insults.