摘要:

AbstractAn attempt was made to transfer a stimulator substance from the perfusate of partially hepatectomized perfused livers to the portal stump of portacaval‐shunted pig recipients. Blood was either cross‐circulated with recipients during perfusion or was given by exchange tranfusion after 4 hr perfusion. There was an increase in thymidine kinase activity and mitotic indices in biopsies from portacaval‐shunted recipients whether perfusions were performed 2 or 4 days after partial hepatectomy. Blood perfused through intact livers did not enhance the regenerative response of portacaval‐shunted pigs; in fact it appeared to suppress the normal small response. Approximately 10% of the portacaval‐shunted recipients died acutely when perfusate was infused into the portal stump. This did not occur if saline or unperfused blood was used suggesting that some toxic substance accumulated during liver perfusion. In end‐stage fulminant hepatic failure, use of blood perfused through a partially hepatectomized animal liver may provide the regenerative stimulus which often appears to

ISSN:0270-9139    

DOI:10.1002/hep.1840010402

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe rates of muscle protein breakdown, as estimated by the urinary excretion of 3‐methylhistidine, were assessed in 30 cirrhotics and 15 controls on a strictly controlled diet. 3‐Methylhistidine excretion was increased in cirrhotics irrespective of the etiology of the disease, and correlated with basal glucagon levels and with the insulin/glucagon ratio. In nine cirrhotics and nine age‐ and sexmatched controls, similar correlations were found between 3‐methylhistidine and the areas under 24‐hr glucagon or insulin/glucagon curves. A larger amount of 3‐methylhistidine was excreted during the nighttime than during the daytime, when glucagon secretion was suppressed and the insulin/glucagon ratio was increased. It is concluded that muscle protein catabolism is increased in cirrhotics, possibly as a result of hyperglucagonemia or the reduced insulin/glucagon ratio. These data agree with the clinical observation of a progressive reduction in lean body mass which becomes evident in an advanced stage of

ISSN:0270-9139    

DOI:10.1002/hep.1840010403

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractStudies were undertaken in 32 patients with hepatitis B‐negative or ‐positive chronic active hepatitis or chronic persistent hepatitis to define the relationship between immunoregulatory activity and the HLA‐B8 and B12 phenotypes. Suppressor T‐cell activity measured by a concanavalin A‐induced suppressor system using allogeneic responder cells was dependent on which individual was selected as a source of responder cells. No differences were noted using isogeneic cells as responders. Suppressor T‐cell activity measured by the effect of a noninduced suppressor cell on a mixed leukocyte culture was not different from controls. Increased prostaglandin‐producing suppressor cell activity was found in patients with hepatitis B‐negative (p<0.005) and hepatitis B‐positive (p<0.05) chronic active hepatitis. When results of the suppressor activities were compared among patients with chronic hepatitis dependent on the presence of HLA‐B8, B12, or neither of these phenotypes, no significant differences were present. These results provide further evidence of altered immunoregulatory function in patients with chronic active hepatitis, which may reflect increased suppression by a population of prostaglandin‐producing suppressor cells. The results do not, however, suggest that a gene coding for altered immune regulation is li

ISSN:0270-9139    

DOI:10.1002/hep.1840010404

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe infusion of a closely related derivative of bilirubin, its dimethyl diester (DME), into jaundiced (jj) Gunn rats was associated with biliary excretion of mono‐and diglucuronides of bilirubin.In vitroincubation of DME with liver microsomes fromjjrats demonstrated sequential demethylation and glucuronidation of DME. Liver microsomes from a patient with the Crigler‐Najjar syndrome were unable to form glucuronides of bilirubinin vitrounless DME was used as substrate. The results suggest that the deficiency in Gunn rats and in the Crigler‐Najjar syndrome may be due to a structural defect in the microsomal matrix which contains glucuronyl transferase. This interpretation envisions a microenvironment of the transferase enzyme which is either impermeable to bilirubin or induces conformational changes which interfere with glucuronid

ISSN:0270-9139    

DOI:10.1002/hep.1840010405

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractLigandin was quantitated by radioimmunoassay in serum and, when possible, in tumors from patients with primary hepatocellular carcinoma, massive hepatic metastasis or nonhepatic primary neoplasms, and in rats and athymic (nu/nu) mice bearing transplantable ligandin‐containing or nonligandin‐containing rat hepatocellular carcinomas.Following transplantation of a ligandin‐containing rat hepatocellular carcinoma in rats or athymic (nu/nu) mice, mean serum ligandin concentrations progressively increased and, within 4 months, exceeded normal serum ligandin concentrations by 10‐fold.In 11 of 15 HBsAg negative patients with primary hepatocellular carcinoma, serum ligandin concentrations ranged from 82 to 551 (mean: 298) ng per ml; the mean ligandin concentration in the hepatic neoplasm was 32% of the ligandin concentration in normal liver. In 19 of 22 patients with extensive hepatic metastasis and in each of 20 patients with primary carcinomas without hepatic metastasis, serum ligandin concentrations were normal (7.0 ± 4.0 ng

ISSN:0270-9139    

DOI:10.1002/hep.1840010406

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe kinetics of plasma clearance of indocyanine green and bromosulfophthalein were studied in 49 consecutive patients with chronic unconjugated hyperbilirubinemia. Forty‐four patients had Gilbert's syndrome whereas five patients had impaired hepatic uptake of indocyanine green and virtually normal hepatic bromosulfophthalein uptake. There was no difference in bilirubin metabolism between the two groups. A family study of the patients with impaired indocyanine green uptake revealed that the defect appears to be transmitted as an autosomal dominant trait associated with inheritance of impaired bilirubin metabolism. These patients manifest a novel disorder of organic anion transport which, like Gilbert's syndrome, is also characterized by chronic mild unconjugated hyperbilirubinemi

ISSN:0270-9139    

DOI:10.1002/hep.1840010407

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe plasma clearance of an i.v. bolus of chenodeoxycholic acid (10 μm per kg) was determined in rabbits with graded degrees of hepatocellular necrosis produced by i.p. injection of carbon tetrachloride. Plasma chenodeoxycholic acid levels were determined by radioimmunoassay, and the volume fraction of necrosis was quantitated by a computerized (Quantimet 720) system. Impaired plasma clearance was observed only when necrosis was extensive, and the volume fraction of necrosis>34%. In contrast, measurement of fasting plasma chenodeoxycholic acid concentration was more sensitive, and elevated levels were associated with a mean volume fraction of necrosis of 12.5%. This study reinforces the conclusion based on clinical studies that measurement of fasting bile acid concentration is a more sensitive discriminant of hepatic dysfunction than is measurement of the plasma clearance of an i.v. bolus of bile acid

ISSN:0270-9139    

DOI:10.1002/hep.1840010408

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe pharmacokinetic disposition of lorazepam was investigated in sham‐operated anesthetized dogs, dogs with hepatic devascularization, and dogs with total splanchnic devascularization following i.v. administration of 0.3 mg per kg of the drug. In sham‐operated dogs, lorazepam distribution was extensive (100 ± 15.2 liters) and clearance approximated expected liver blood flow (971 ± 91 ml per min). Lorazepam glucuronide levels in plasma rose rapidly in the first hour and reached a plateau by 5 hr. Urinary recovery of the conjugate in 5 hr was 45% of administered dose. Hepatic devascularization resulted in 39% reduction in distribution volume, and 89% reduction in clearance; however, there was still 105 ± 88 ml per min of extrahepatic lorazepam clearance. Five‐hour urinary recovery of conjugate decreased by 80%. Total splanchnic devascularization resulted in 37% further reduction in extrahepatic clearance, almost complete inhibition of urinary recovery of conjugate, and further reduction in the volume of distribution. It is concluded that the liver is the major site for lorazepam metabolism in dogs; however, appreciable extrahepatic metabolism occurs, partly in nonhepatic components of the splanchnic organs which act as a reservoir during drug dist

ISSN:0270-9139    

DOI:10.1002/hep.1840010409

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe effects of chronic ethanol consumption and variations in dietary protein content on microsomal drug metabolism were studied in rats pair‐fed liquid diets containing 10, 20, or 30% dietary protein with or without ethanol.In vivodrug metabolism was measured by aminopyrine breath tests and aminopyrine blood elimination kinetics.In vitrodrug metabolism was assessed by measuring aminopyrineN‐demethylase activity in the hepatic microsomal fraction. The rate of elimination of aminopyrinein vivowas increased in all ethanol‐fed animals (p<0.05) regardless of the protein content of the diet. Animals receiving 10 or 20% protein diets with ethanol showed a 36% increase in drug elimination over pair‐fed controls as compared to a 17% increase in drug elimination over controls in animals receiving 30% protein diets. Microsomal aminopyrineN‐demethylase activities were similar in ethanol‐fed animals and pair‐fed controls. Cytochrome P‐450 content was increased in all ethanol‐fed animals (p<0.05) but the increase was not dependent on dietary protein content. These results indicate that the effect of chronic ethanol feeding in enhancing drug metabolismin vivois influenced by the dietar

ISSN:0270-9139    

DOI:10.1002/hep.1840010410

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractValproic acid (VPA) is an anticonvulsant agent which produced marked choleresis in the rat. Bile flow rate increased from 50 to 60 μl per min per kg to 120 to 145 μl per min per kg immediately after i.v. injection of VPA (37.5 to 150 mg per kg; 2 ml per kg) in male Sprague‐Dawley rats. The duration of maximal bile flow was dose‐dependent and increased from 30 min (37.5 mg VPA per kg) to approximately 2 hr (150 mg VPA per kg). Choleresis diluted the biliary concentrations of bile acids, Cl−, cholesterol, and phospholipids. VPA did not change the bile/plasma ratio for erythritol suggesting that the increased bile flow is of canalicular origin. VPA did not influence the excretion of bile acids or their osmotic activity, whereas bile salt‐independent flow doubled in rats treated with 150 mg VPA per kg. The bile/plasma, bile/liver, and liver/plasma concentration ratios for VPA were 11.7, 1.6, and 7.3, respectively. Approximately 90% of VPA appearing in bile was biotransformed, primarily as a glucuronide. Bile flow correlated with VPA excretion; 16 μl of bile was produced per μmole VPA which suggests that choleresis is primarily due to the osmotic activity of VPA metabolites in bile. VPA enhanced the excretion of inorganic ions which may also contribute to choleresis. Biliary excretion of phenol‐3,6‐dibromophthalein disulfonate and ouabain was unaffected. Thus, VPA is an effective choleretic which stimulates bile salt‐independent flow of canalicular origin largely as a consequence of the osmotic properties of VPA c

ISSN:0270-9139    

DOI:10.1002/hep.1840010411

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY