摘要:

AbstractThe uptake of radiocopper by HepG2 cells is a saturable, temperature‐dependent and cellular energy‐independent process with a Vmaxof 7.1 ± 0.2 pmoles min−1mg protein−1andan estimated Kmof 3.3 ± 0.5μM. The rate of copper uptake is reduced at an equimolar concentrationof albumin and is unaffected by zinc at a 10‐fold molar excess. Approximately 70% of the newly incorporated radiocopper binds to membranes and organelles, while 30% is recovered in the cytosol. The soluble fraction can be resolved intotwo copper‐binding protein peaks. Incubation of HepG2 with nonisotopic copper results in displacement of radiocopper associated with the proteins contained in the lower molecular weight peak. Exposure of the cells to cycloheximide inhibits the incorporation of the isotope into

ISSN:0270-9139    

DOI:10.1002/hep.1840060112

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractAlthough primary hepatoma is not very frequent in alcoholics, the incidence of hepatoma in cases of hepatitis B infection combined with heavy alcohol drinking is high. In the present study, the effects of chronic alcohol administration onthe development of chemicalinduced hepatic cancer in rats were analyzed. In 70% hepatectomized Wistar strain male rats, asingle dose (1 mg per 100 gm body weight) of diethylnitrosamine was injected intraperitoneally. Eight weeks after the injection, 20% alcohol‐10% sucrose solution (diethylnitrosamine‐alcohol group), 0.1% sodium phenobarbital solution (diethylnitrosamine‐phenobarbital group), 10% sucrose solution (diethylnitrosamine‐sucrose group) or tap water (diethylnitrosamine‐alone group) was given as drinking water for 32 weeks. The numbers of visible nodules per liver were significantly greater in the diethylnitrosamine‐alcohol and diethylnitrosamine‐phenobarbital groups compared to the diethylnitrosaminealone and diethylnitrosamine‐sucrose groups. The numbers of enzyme‐altered foci which were positive to γ‐glutamyl transpeptidase staining per square centimeter of liver section were also greater in the diethylnitrosamine‐alcohol and diethylnitrosamine‐phenobarbital groups than in the diethylnitrosamine‐alone and diethylnitrosamine‐sucrose groups, although the numbers of nodules and enzyme‐altered foci were significantly larger in the diethylnitrosamine‐phenobarbital group than in the diethylnitrosamine‐alcohol group. The enzyme‐altered foci areas calculated by γ‐glutamyl transpeptidase staining were significantly larger in the diethylnitrosamine‐alcohol and diethylnitrosamine‐phenobarbital groups than in the diethylnitrosamine‐alone and diethylnitrosamine‐sucrose groups. Histologically, visible nodules observed in diethylnitrosamine‐phenobarbital and diethylnitrosamine‐alcohol groups showed characteristic features of neoplastic nodules. These results indicate that alcohol has a promoter action on the development of c

ISSN:0270-9139    

DOI:10.1002/hep.1840060113

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractAcute fulminant hepatitis was induced in 55 healthy adult male rabbits with the potent hepatotoxin galactosamine hydrochloride (3.75 mmoles per kg i.v.). Control rabbits (n = 27) were divided into three groups: Group I (n = 10) underwent sham surgery for placement of an indwelling central venous catheter; Group II (n = 9) received 5% dextrose and water via an indwelling central venous catheter, and Group III (n = 8) received daily intramuscular injections of 0.9% sodium chloride. Treated rabbits (n = 28) also consisted of three groups: Group IV (n = 9) received 12‐hr intravenous infusions of insulin (0.029 units per kg per hr) and glucagon (2.86 μg per kg per hr) daily; Group V (n = 10) received a continuous infusion of parenteral amino acids (Travasol), and Group VI (n = 9) received daily intramuscular methylprednisolone (0.69 mg per kg). In each case, treatment was initiated 16 hr following galactosamine injection. Serum aminotransferase activity was determined on Days 0, 1, 4 and 10 of the 10‐day study. Liver histology was obtained immediately after death and graded under code on a scale of 1 to 4 for severity of hepatitis. Rabbits surviving 10 days were sacrificed on Day 10 for histologic examination.The extent of galactosamine‐induced hepatic injury was similar in all six groups as manifest by peak mean SGPT(range: 2,662 to 3,568 IU per liter), SGOT (range: 4,435 to 5,625 IU per liter) levels and hepatic histologic findings. The overall survival rate in controls was 6/27 (22%); in insulin/glucagon‐treated animals 2/9 (22%), and in the amino acid‐treated group 2/10 (20%). The corticosteroid‐treated group, however, had significantly improved survival: 6/9 (67%, p0.05). In conclusion, the results of this study indicate that in this animal model of acute fulminant hepatitis and withthese doses, insulin/glucagon infusions and parenteral amino acids have no beneficial effect, while high dose corticosteroids significantly enhance survival. On the basis of these results, a reappraisal of the use of high dose corticosteroidsin the treatment of nonviral forms of acute fulminant heptitis in humans would appea

ISSN:0270-9139    

DOI:10.1002/hep.1840060114

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractIn a study of severe, decompensated liver failure, we tried to find a correlation between hemorrhage and parameters ofhemostasis and fibrinolysis. Three groups of patients were studied: alcoholic cirrhosis; nonalcoholic cirrhosis, and acute liver failure without known prior liver disease. The two cirrhotic groups did not differ significantly from each other in coagulation or in fibrinolytic parameters, although liver function was more impaired in nonalcoholic cirrhosis. The levels of clotting factors, antithrombin III, prekallikrein, plasminogen and α2−antiplasmin were significantly lower in the third group. Mean values of fibrinolytic activity (fibrin plate method) were slightly reduced as compared to normal in all three groups. Tissue plasminogen activator‐related antigen tended to be elevated especially in alcoholic cirrhosis. The free fast‐acting plasminogen activator inhibitor showed extremely high and extremely low levels in some patients among all three groups.Nonvariceal, capillary‐type bleeding, including mucosal bleeding, hematomas and bleeding from puncture sites correlated with low thrombotest and normotest levels (p<0.01), low fibrinogen concentration (p<0.05) and with a high quotient of fibrinolytic activity (square root of lysis area) and normotest (p<0.001). The ratio between fibrinformation and dissolution appears to be an important parameter of hemorrhagic tendency in liver disease. Variceal bleeding appeared not to be related to impairment of hemostasis or fibr

ISSN:0270-9139    

DOI:10.1002/hep.1840060115

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractHepatic blood flow and estimated hepatic oxygen consumption were studied in rats treated chronically with ethanol by organ‐reflectance spectrophotometry and the hydrogen clearance method.In the withdrawal state from ethanol, the concentration of hemoglobin in the hepatic tissue (ΔEr569—650), the estimated hepatic oxygen consumption (estimated VO2) and the regional liver blood flow decreased significantly in rats treated chronically with ethanol in comparison with their controls. On the other hand, there was no significant difference in the estimated oxygen saturation of the hepatic blood hemoglobin (estimated SO2) between both groups. That is, an increase in oxygen extraction, which was exhibited by a decrease in the estimated SO2, did not occur in rats treated chronically with ethanol in spite of a decrease in blood supply.Thus, in the withdrawal state from ethanol, both oxygen delivery to the liver and oxygen utilization in the liver weredisturbed at the stage of alcoholic fatty l

ISSN:0270-9139    

DOI:10.1002/hep.1840060116

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractPropranolol has been reported to reduce portal and wedged hepatic vein pressures in man and may be useful for the prevention of variceal bleeding. However, its mechanism of action remains unclear. We have examined the effect of propranolol on the systemic and hepatic circulations in dogs with chronic bile duct ligation and secondary biliary cirrhosis. Underanesthesia, eight dogs received four increasing doses of propranolol as an i.v. bolus followed by continuous infusion. Systemic and hepatic hemodynamic parameters were measured in basal conditions and after a 30 min infusion for each dose. Portal vein and hepatic artery blood flows were measured with electromagnetic flow meters. All dogs had portal hypertension(portal venous pressure 15.3 ± 0.8 mm Hg), a hyperdynamic circulation and severe liver disease resulting in a marked decrease of propranolol systemic clearance (8.75 ml per min per kg) and extraction (40%). The first dose of propranolol induced a decrease in heart rate (–27%) and in cardiac index(–21%), and an increase in systemic vascular resistance (+20%). With increasing doses, the systemic vascular resistance decreased with an increase in the cardiac index. Propranolol was not associated with significant modifications of hepatic hemodynamics: portal, wedged and free hepatic venous pressures and hepatic artery blood flow were stable, and portal blood flow decreased slightly at very high propranolol levels. In seven dogs studied without dissection of the hepatic vessels, there was a small decrease in portal pressure, but not in wedged and free hepatic venous pressures with increasing doses of propranolol. Thus, in dogs with intrahepatic portal hypertension, propranolol has significant effects on systemic hemodynamics, but only minimal effects on the hepatic circula

ISSN:0270-9139    

DOI:10.1002/hep.1840060117

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe portal venous‐esophageal luminal pressure gradient may be more important than the absolute portal venous pressure in explaining hemorrhages caused by esophageal varices. A continuous recording of portal venous pressure and the esophageal luminal pressure enabled the authors to study the gradient between these pressures in 12 cirrhotic patients with varices of different size and under different circumstances, in particular inspiration, expiration, coughing and a Valsalva maneuver.A significant increase of portal venous pressure occurred during inspiration (+15%), coughing (+77%) and Valsalva maneuver (+157%). The value of portal venous‐esophageal luminal pressure gradient increased during inspiration (+38%), coughing (+90%) and Valsalva maneuver (+69%) while it decreased during expiration (

ISSN:0270-9139    

DOI:10.1002/hep.1840060118

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe present study was designed to investigate the effect of propranolol on portal pressure of patients with alcoholic cirrhosis and portal hypertension and to correlate these effects with clinical and laboratory parameters. The mean baseline hepatic venous pressure gradient in the 50 patients studied was of 18.2 ± 4.1 mm Hg. It decreased significantly2 hr after the oral administration of 40 mg of propranolol to 15.7 ± 4.2 mm Hg (a mean reduction of 13.4 ± 17%). This reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure. There was no correlation between the decrease in hepatic venous pressure gradient and the decrease in heart rate. When results were analyzed individually, only 15 (30%) showed a large decrease in hepatic venous pressure gradient (>20%), 15 (30%) showed a moderate decrease (10 to 19%), and in 20 patients (40%) there was no reduction or an increase in hepatic venous pressure gradient. Comparison of “responders” (those that reduced hepatic venous pressure gradient>10%) and “nonresponders” (hepatic venous pressure gradient reduction<10%) showed no significant differences in baseline laboratory and hemodynamic parameters, in the severity of the liver disease, in theheart rate and blood pressure response to propranolol, nor in the propranolol plasma levels achieved 2 hr after propranolol administration. Propranolol plasma levels correlated with the reduction in heart rate but not with the reduction in hepatic venous pressure gradient. Of 14 nonresponders to 40 mg of propranolol who received additional doses, six showed a reduction inhepatic venous pressure gradient.We conclude that, although propranolol reduces the mean portal pressure in patients with alcoholic cirrhosis and portal hypertension, this response is not uniform. Twenty percent of cirrhotic patients do not show any reduction in portal pressure even after maximal doses of propranolol. There is no clear explanation for this variable response; pharmacologic and/or hemodynamic factors may be involved. Neither the heart rate response to propranolol nor the propranolol plasma concentrations were found to be useful in assessing the portal pressure response to p

ISSN:0270-9139    

DOI:10.1002/hep.1840060119

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractIsosorbide dinitrate, a long‐acting vasodilator, has been tested in human portal hypertension with conflictingresults. In order to determine some of the factors that could affect the individual response to this drug, we infused isosorbide dinitrate at a low dose (10 to 25 μg per kg per min) and a high dose (100 μg per kg per min) to rats with portal vein stenosis. Under pentobarbital anesthesia, portal pressure was measured with an ileocolic vein catheter while cardiac output and regional blood flows were measured with the microsphere technique. At a dose that decreased arterial pressure by approximately 10%, cardiac output remained unchanged while portal vein inflow decreased significantly; portal pressure was not reduced (10.7 ± 0.2 vs. 10.0 ± 0.3 mm Hg), indicating a rise in portal vascular resistance. At a high dose of isosorbide dinitrate, arterial pressure and cardiac output fell markedly; portal pressure decreased only modestly (11.3 ± 0.3 vs. 9.8 ± 0.6 mm Hg, p<0.05), but portal flow was unchanged, indicating a reduction in portal vascular resistance. In addition, portal hypertensive rats received a constant i.v. infusion ofN‐acetyl‐cysteine the combination of the latter and isosorbide dinitrate markedly potentiated the effects on arterial pressure. Thus, the dose of the drug and the presence of cysteine‐containing compounds appear to modulate the hemodynamic response to isosorbide dinitrate. Clinical testing with this drug should be undertaken with consideration of

ISSN:0270-9139    

DOI:10.1002/hep.1840060120

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe effect of terlipressin (N‐α‐triglycyl‐8‐lysinevasopressin) in bleeding esophageal varices was evaluated in a prospective placebo‐controlled study. Fifty bleeding episodes from esophagealvarices in 34 patients were randomized. Standard therapy with transfusions, fluid and electrolyte correction, and lactulose was performed in both groups. Balloon tamponade was used in 20 bleeding episodes in the terlipressin group and in 19 bleeding episodes in the control group.In the terlipressin group, hemorrhage was controlled in all bleeding episodes (25/25) whereas in the placebo group, only 20 of 25 bleeding episodes could be stopped within 36 hr (p<0.05). Sclerotherapy was performed in five bleeding episodes in the terlipressin group and in seven bleeding episodes in the placebo group. Treatment failures, including patients who required sclerotherapy, occurred in five bleedings in the terlipressin group and in 12 in the control group (p<0.05). The hospital mortality rate was 12% (3/25) in the terlipressin group and 32% (8/25) in the control group. Patients in the terlipressin group required fewer transfusions, the balloon needed to be inflated for a shorter time and theduration of bleeding was shorter than in the control group. However, these differences were not significant.These data do not allow conclusions concerning monotherapy with terlipressin, but they indicate that the addition of terlipressin to standard therapy may increase the control rate in acute variceal

ISSN:0270-9139    

DOI:10.1002/hep.1840060121

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY