Biomedical subjects

Y Shibayama

Publications and source records attributed to Y Shibayama.

At least 73 records · Page 4Linked to original sources

PubMed1992

Haemodynamic alterations and their morphological basis in biliary obstruction.

The relationship between the haemodynamic alterations and morphological changes in the liver caused by biliary obstruction was investigated in rats after ligation of the common bile duct. In these rats, the portal vein pressure was markedly elevated, and the differences in blood pressure between the portal vein and the terminal portal venule and between the terminal portal venule and the terminal hepatic venule were greater than in the sham-operated rat. The livers showed narrowing of the most peripheral branches of the portal vein due to compression by proliferated bile ductules and sinusoidal stenosis due to enlarged liver cells, but there was no perceptible change in the hepatic vein branches. These data suggest that hepatic circulatory disturbance in biliary obstruction is caused by deformation of the peripheral portal vein branches and sinusoidal stenosis.

Animals↗

PubMed1991

Recovery from hepatic necrosis following acute portal vein embolism with special reference to reconstruction of occluded vessels.

We examined the morphological and haemodynamic changes in the livers of rats following acute obstruction of portal vein branches by the injection of agar into the portal vein. Histological and angiographic examinations of the liver were performed after measurements of portal vein pressure in vivo and portal vascular resistance by an isolated liver perfusion method. Portal vein embolism induced hepatic necrosis in the centrilobular and midzonal areas, which was rapidly resorbed and replaced by regenerated liver cells leaving no trace. This recovery from hepatic necrosis was closely related to recanalization of obstructed portal vein branches, which led to falls in both the elevated portal vein pressure and the increased portal vascular resistance following embolization.

Acute Disease↗

PubMed1991

Focal veno-occlusive lesions following metastasis of cancer in the liver with special reference to obstruction of lymphatics in hepatic veins.

Focal veno-occlusive lesions and congestion of the liver are found frequently at autopsy in patients with metastatic carcinoma in the liver. In 6 cases, intimal proliferation of loose connective tissue with dilatation of lymphatic capillaries was seen continuously from the terminal hepatic venule to the hepatic vein, and cancer cells were found only in lymphatic capillaries in the wall of the hepatic vein. In 7 cases, cancer cells infiltrated directly into the adventitia of the sublobular vein and intimal proliferation of loose connective tissue with or without formation of recent thrombi was observed. A main causative factor of hepatic veno-occlusive disease is thought to be leakage of plasma due to endothelial injury to the terminal hepatic venule and sublobular vein. Lymphatic obstruction, in addition to a direct reaction to invasion of cancer cells to the vessel wall, may also cause veno-occlusive lesions due to stasis and leakage of lymph fluid into the intima of the terminal hepatic venule, sublobular vein and hepatic vein.

Adult↗

PubMed1991

Mechanism of liver injury following ischemia.

To clarify whether ischemic liver injury is due to ischemia itself or reperfusion, histopathological and functional changes in the liver were examined before and after liver ischemia in rats with porto-systemic collateral channels. Effects of oxygen-derived free radical scavengers or an inhibitor of platelet aggregation on development of ischemic liver injury were also examined. Liver ischemia was produced by ligation of the portal vein and hepatic artery at liver hilum for 1 hr. The primary lesion of ischemic liver injury was cloudy swelling of liver cells in the periportal and midzonal regions; it developed during ischemia. The cloudy swelling of liver cells induced uneven distribution of sinusoidal blood flow after reperfusion, and consequently individual liver cell necrosis and focal hepatocellular necrosis in the midzonal regions developed later. Elevation of cytoplasmic enzyme activities in the serum after reperfusion was due to leakage across the damaged plasma membrane of liver cells. The treatment with superoxide dismutase, catalase, or heparin had not altered the liver injury that was attributed to ischemia, biochemically and histologically. These results suggest that ischemic liver injury is due to liver cell damage developed during ischemia, and that the ischemic liver injury is not alleviated or prevented by superoxide dismutase, catalase, or heparin.

Alanine Transaminase↗

PubMed1991

The pathogenesis of hyaline globules in liver cells after partial hepatectomy in rats.

To clarify the pathogenesis of hyaline globules in liver cells after partial hepatectomy, the present study was undertaken in rats. When partial hepatectomy was performed by the surgical procedure of Higgins and Anderson, the inferior vena cava pressure was raised, and many hyaline globules, which are very similar to those caused by condensation of the contents of vacuoles in liver cells after temporary pressure elevation of the inferior vena cava, were induced in liver cells. On the other hand, when the median lobe and the left lateral lobe were removed carefully one at a time to avoid operative narrowing of the inferior vena cava, the inferior vena cava pressure was not elevated, and only very few hyaline globules were formed. This suggests that hyaline globules in liver cells following partial hepatectomy in rats may be caused by elevation of inferior vena cava pressure due to narrowing of the inferior vena cava by surgical procedure.

Animals↗

PubMed1991

Endotoxin hepatotoxicity augmented by ethanol.

To determine whether alcohol increases endotoxin hepatotoxicity, we administered ethanol (4.8 g/kg body wt in 4 ml of water) to rats through a gastric tube, then immediately injected endotoxin (2, 2.5, or 3 mg/kg body wt). In the rats pretreated with ethanol, the injection of 2 mg/kg body wt of endotoxin induced a slight rise of serum transaminase. However, when 2.5 mg/kg body wt of endotoxin was given, there were no significant histopathological or biochemical differences between the rats pretreated with ethanol and those pretreated with water. Moreover, there was no significant difference in mortality rates between the rats pretreated with ethanol and the controls when 3 mg/kg body wt (LD50) of endotoxin was injected. These results suggest that acute administration of alcohol enhances endotoxin hepatotoxicity when the dose of endotoxin is small, but that the effect of alcohol is masked when larger doses of endotoxin are given.

Animals↗

PubMed1991

Relation of the reticuloendothelial function to endotoxin hepatotoxicity.

The present study was undertaken in rats to clarify whether endotoxin hepatotoxicity can be modified by phagocytic activity of the reticuloendothelial system. Pretreatment with cortisone acetate, diethylstilbestrol, methyl palmitate, triolein or gadolinium chloride markedly improved the mortality rate from endotoxemia and prevented the development of focal random coagulative hepatocellular necrosis and the elevation of serum transaminase activities due to endotoxemia. Cortisone acetate, methyl palmitate and gadolinium chloride are the well-known depressors of reticuloendothelial phagocytic activity: Diethylstilbestrol and triolein are the stimulators. This suggests that phagocytic activity of the reticuloendothelial system does not relate to not only the mortality rate but also the degree of hepatic injury following endotoxemia.

Animals↗

PubMed1991

Possible role of tumor necrosis factor and interleukin-1 in the development of diabetic nephropathy.

The possibility that tumor necrosis factor (TNF) and interleukin-1 (IL-1) could participate in the development of diabetic nephropathy was evaluated in streptozocin (STZ)-treated diabetic rats. Diabetic rats were divided into two groups: aminoguanidine treated group (25 mg/kg body wt, daily i.p. injection; DM-AG group) and untreated group (DM group). Non-diabetic age-matched rats were also divided into two groups with the same manner and used as controls. After twelve weeks of treatment, glomerular basement membranes (GBM) were isolated from rats of each experimental group. When thioglycollate-elicited peritoneal macrophages (M phi) from normal rats were incubated with these GBM materials, GBM from DM group induced significantly greater levels of TNF and IL-1 production than did GBM from other three groups with at doses of 2.5 to 10 mg. The TNF and IL-1 production by stimulation of GBM from the DM-AG group were similar to those from each control group. Aminoguanidine treatment significantly decreased the accumulation of advanced glycation end-products (AGEs) in GBM of diabetic rats. These findings suggest that AGE-proteins may be involved in the production of TNF and IL-1 from M phi. AGE-induced cytokines may be implicated in the development of diabetic nephropathy.

Albuminuria↗

PubMed1991

The role of pericentral fibrosis in experimental portal hypertension in rats.

To clarify the relation of pericentral fibrosis to portal hypertension, measurements of portal vascular resistance in vitro and blood pressures of several key points in hepatic vascular pathways in vivo were undertaken in rats given dimethylnitrosamine. Administration of dimethylnitrosamine induced tortuosity and narrowing of the peripheral branches of the hepatic vein due to pericentral fibrosis. No significant change was produced in the sinusoids and the portal vein branches. The portal vascular resistance was increased and the portal vein pressure was elevated markedly. The blood pressure gradient was steep in the intrahepatic vein, but not in the intrahepatic portal vein or the sinusoids, as compared to control. These data suggest that deformation of the peripheral branches of the hepatic vein due to pericentral fibrosis causes a marked increase in vascular resistance in the intrahepatic hepatic vein, i.e. postsinusoidal portal hypertension.

Animals↗

PubMed1990

Factors producing bile infarction and bile duct proliferation in biliary obstruction.

To clarify the factors producing bile infarction and bile duct proliferation in obstructive jaundice, the incidence of the hepatic lesions and the serum levels of the bile constituents were examined in three rat models. (1) Ligation of the common bile duct induced bile infarction, bile duct proliferation, retention of bile in the liver, and elevation of the serum levels of total bilirubin and total bile acids. (2) The rats treated by choledochotomy had bile in the abdominal cavity, but there was no retention of bile in the liver. The degree of development of bile infarction was similar to that of the common bile duct ligation group, but bile duct proliferation was not found: the serum levels of total bilirubin and total bile acids were elevated. (3) In the rats subjected to partial bile duct ligation, bile infarction and bile duct proliferation were seen only in the lobes with ligation of the hepatic ducts: only slight or no elevation of the serum levels of total bilirubin and total bile acids was found. These data suggest that bile infarction is caused by the toxic action of bile constituents other than bilirubin and bile acids, absorbed into the blood from the obstructed biliary system, and that bile duct proliferation is due to mechanical factors following bile retention or direct actions of retained bile in the liver.

Alanine Transaminase↗

PubMed1990

The relation of endotoxaemia to the cause of death and fatal hepatic damage following obstruction of the portal vein.

The present study was undertaken in rats with portosystemic collaterals to clarify whether portal vein occlusion induces fatal hepatic damage and whether endotoxaemia relates to development of lethal hepatic failure following portal vein obstruction. Sudden portal vein occlusion caused severe hepatic necrosis and hepatic dysfunction. However, the mortality rate was only 14 per cent, and the hepatic damage recovered 1 week later. Administration of endotoxin immediately after portal vein ligation induced a high mortality rate (86 per cent): the cause of death was thought to be systemic circulatory failure. Endotoxin administration 1 week after portal vein ligation caused marked hepatic dysfunction and hepatic necrosis, but no deaths occurred. These experimental data suggest that hepatic damage following sudden portal vein occlusion is temporary and not fatal provided that portosystemic shunts form adequately. However, it is lethal when complicated by endotoxaemia. Severe hepatic damage and death in chronic portal vein occlusion with portosystemic collaterals cannot be attributed solely to portal vein occlusion, and other factors such as endotoxaemia may play an important role in their development.

Animals↗

PubMed1990

Role of endotoxaemia in the development of hepatic failure following hepatic artery occlusion.

The present study was undertaken to examine whether endotoxemia relates to the development of hepatic failure following surgical ligation or embolization of the hepatic artery. A small amount of endotoxin was given immediately or 1 week after hepatic artery ligation in rats, and liver function tests and morphological examination of the liver were performed at 24 h after the administration. Hepatic artery ligation alone or endotoxin administration alone did not induce functional and morphological alteration of the liver. However, when endotoxin was given immediately after hepatic artery ligation, there was an increase in serum transaminase activity and focal hepatocellular necrosis developed. On the other hand, when endotoxin was given 1 week after hepatic artery ligation, the hepatic injury was not induced because of the development of hepatic arterial collaterals. These data suggest that endotoxaemia may be a cause of hepatic failure following hepatic artery occlusion, and that the risk may persist until the establishment of hepatic arterial collaterals.

Animals↗

PubMed1990

Role of sinusoidal pressure in the development of vacuolation in liver cells.

Vacuolation of liver cells, which is often seen in patients with right-sided heart failure, is sometimes confused with fatty change, but the contents are components of blood. This study was undertaken using an isolated rat liver perfusion model to clarify the pathogenesis of vacuolation of liver cells. It has been demonstrated that (1) hypoxia alone cannot cause vacuolation; (2) elevation of the sinusoidal pressure leads to vacuoles in liver cells, irrespective of the oxygen content of the perfusate; and (3) the number and size of vacuoles are proportional to the height of the sinusoidal pressure, but not to the oxygen content of the perfusate. The reason why vacuolation generally appears in the pericentral area in patients with right-sided heart failure may be that the sinusoidal pressure in this area rises in parallel with the inferior vena cava pressure.

Animals↗

PubMed1990

The fate of vacuolation in liver cells with special reference to hyaline globules.

This study was undertaken in rats to clarify the mechanisms and time necessary for recovery from vacuolation in liver cells. Vacuoles were produced by congestion of the liver due to constriction of the inferior vena cava just below the diaphragm, and changes in vacuoles were examined quantitatively and qualitatively until 24 h after release of the constriction. Vacuoles in liver cells decreased in number by half within 5 min after recovery from congestion. The remaining vacuoles metamorphosed to hyaline globules by condensation of the contents. The number of hyaline globules increased with a peak occurring at 3-6 h after recovery from congestion, although the number of vacuoles decreased gradually. Only a few small vacuoles and hyaline globules were found in liver cells in pericentral areas at 24 h after recovery from congestion. These data indicate that vacuoles may be discharged promptly from the liver cell cytoplasm after recovery from congestion, and the remaining vacuoles may metamorphose to hyaline globules by condensation of the contents and finally fade into the cytoplasm.

Animals↗

PubMed1990

The relation of periportal fibrosis to portal hypertension.

To clarify the relation of periportal fibrosis to portal hypertension, the present study was undertaken in rats given lithocholate. Portal vascular resistance measured by an isolated liver perfusion method increased with the length of lithocholate administration. In vivo portal vein pressure elevation was closely correlated to the increase in portal vascular resistance. The blood pressure difference between the portal vein and the terminal portal venule increased compared to control rats. The blood pressure differences between the terminal portal venule and the terminal hepatic venule, and between the terminal hepatic venule and the inferior vena cava, were almost the same as those in control rats. Lithocholate administration induced narrowing and meandering of the portal vein branches due to periportal fibrosis with proliferation of bile ductules. There was no perceptible change in the sinusoids and the hepatic vein branches. These data suggest that periportal fibrosis causes deformation of the peripheral branches of the portal vein and leads to presinusoidal portal hypertension.

Administration, Oral↗

PubMed1989

Endotoxaemia and hepatic injury in obstructive jaundice.

To examine whether endotoxaemia contributes to the development of bile infarction and whether obstructive jaundice enhances endotoxin hepatotoxicity, the present study was undertaken in rats. The development of bile infarction and the elevation of serum transaminase activities in rats following ligation of the common bile duct were not prevented by administration of polymyxin B, neomycin, or lactulose, which have anti-endotoxin properties. Moreover, the morphological and functional changes in obstructive jaundice were not enhanced by administration of endotoxin. These data indicate that endotoxaemia does not contribute to the development of bile infarction. On the other hand, the administration of a small dose of endotoxin to rats with biliary obstruction--a dose which does not induce abnormalities of liver function tests or any morphological changes in the liver in non-jaundiced rats--led to focal hepatocellular coagulative necrosis and elevation of serum transaminase levels. These data indicate that endotoxin-induced hepatic injury is potentiated in obstructive jaundice.

Animals↗

PubMed1989

Prevention of hepatotoxic responses to chemicals by glycyrrhizin in rats.

To clarify whether glycyrrhizin, the aqueous extract of licorice root and a drug for treatment of chronic active hepatitis, prevents the development of hepatic injury induced by carbon tetrachloride, allyl formate, and endotoxin, the present study was undertaken in rats. The treatment with glycyrrhizin 20 hr before carbon tetrachloride administration protected the development of the pericentral hepatocellular necrosis. Glycyrrhizin treatment 2 hr prior to the administration of allyl formate also inhibited the development of the periportal hepatocellular necrosis. However, glycyrrhizin did not protect the development of endotoxin-induced focal and random hepatocellular necrosis. These experimental results suggest that glycyrrhizin has no protective effect on hepatic injury following sinusoidal circulatory disturbance as seen in the case of endotoxin and that glycyrrhizin can protect against hepatotoxicity induced by the direct action on the hepatocytes due to hepatotoxins, such as carbon tetrachloride and allyl formate.

Alanine Transaminase↗

PubMed1989

Simple method for determination of A1c-type glycated hemoglobin(s) in rats using high performance liquid chromatography.

We have developed a new chromatographic method for the determination of rat glycated hemoglobins by cation exchange high-performance liquid chromatography. The hemoglobins were eluted by a two-step gradient, and the total assay time, including re-equilibration of the column, was 27 min. Two A1c type and one pre-A1c type rat glycated hemoglobins were separated and measured. The change in major HbA1c of rats, in which diabetes was induced by streptozotocin and which were subsequently treated with insulin, was monitored. In diabetic rats (n = 10, average blood glucose greater than 300 mg/dL), major HbA1c rose to 3.39 +/- 0.06% compared with controls (n = 10, 1.20 +/- 0.03%) during 5 wk. Insulin treatment decreased the HbA1c from 3.48 +/- 0.16% to 2.74 +/- 0.15% (p less than 0.01) in 6 wk. This method was also effective for the determination of mouse HbA1c.

Animals↗