摘要:

AbstractTo study the effect of chronic alcohol consumption on hepatic levels of thyroid hormones, female Sprague‐Dawley rats (n = 24) were pair‐fed nutritionally adequate liquid diets containing either ethanol (36% of total calories) or isocaloric carbohydrates for 21 days. Compared to controls, chronic alcohol consumption failed to result in a significant change of hepatic thyroid hormone levels (thyroxine: 14.7 ± 1.81 ng per gm of liver wet weight vs. 15.0 ± 1.59; triiodothyronine: 2.60 ± 0.16 ng per gm of liver wet weight vs. 2.66 ± 0.18). Similar results were obtained when the hepatic levels of thyroid hormones were expressed per total liver, per gram of liver protein or per 100 gm of body weight. Moreover, prolonged alcohol ingestion led to a significant reduction of serum total thyroxine by 31.6% (p ± 0.001), free thyroxine by 38.9% (p ± 0.02), total triiodothyronine by 40.2% (p ± 0.001) and free triiodothyronine by 56.1% (p ± 0.001) when compared to their pair‐fed controls, whereas thyroid‐stimulating hormone levels remained virtually unchanged. These data, therefore, clearly show that chronic alcohol consumption is incapable of creating a hyperthyroid hepatic state in rats, and limit the rationale for antithyroid treatment in patients with alcoholi

ISSN:0270-9139    

DOI:10.1002/hep.1840030401

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY

摘要:

AbstractThe influence of intravenous infusion of branched‐chain amino acids (BCAAs) on brain function in patients with liver cirrhosis and acute hepatic encephalopathy was examined using a double‐blind, randomized study design. Five medical centers in France and Sweden participated, and 50 patients were studied. The patients received either BCAAs (40 gm per day) in 5% glucose or 5% glucose alone (placebo) for 5 days or until “wake up”. Nutritional support was provided with equal proportions of carbohydrate and fat. During BCAA adminstration, plasma concentrations of aromatic amino acids and methionine fell (20 to 40%, p<0.05 to 0.01), and the ratio of BCAAs to aromatic amino acid concentrations increased significantly. Clinical improvement was seen in 14 of 25 BCAA‐treated patients and in 12 of 25 patients receiving placebo (N.S.). EEG responses were similar in the two groups during treatment. In the BCAA group, 10 of 25 patients died in the course of the study, compared to 5 of 25 in the placebo group (N.S.); six patients died from encephalopathy in the BCAA group as compared to three among placebo‐treated patients. It is concluded that BCAA adminstration, in the dose and composition employed in the present study, reduces the concentrations of aromatic amino acids but neither improves cerebral function nor decreases mortality in patients with hepatic enc

ISSN:0270-9139    

DOI:10.1002/hep.1840030402

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY

摘要:

AbstractWe studied changes in hepatic membrane (Na+,K+)ATPase activity and membrane lipids induced by canrenoate, the water‐soluble congener of canrenone, the active metabolite of spironolactone. (Na+,K+)ATPase activity was decreased after canrenoate in a dose‐ and time‐dependent manner. Decreased activity was demonstrated at the lowest dose (91% of control after 5 μmoles per 100 gm body weight per day × 3 days); the maximum dose (30 μmoles per 100 gm body weight per day × 3 days) resulted in activity 38% of untreated control values. A 20 μmoles per 100 gm body weight per day dose decreased enzyme activity to 89 and 55% of control after 24 and 72 hr, respectively. The nonionic detergent Triton WR‐ 1339 partially reversed drug‐induced inhibition, suggesting that the enzyme changes may be related to altered membrane lipids.Membrane cholesterol increased 17% after 3 days of 30 μmoles canrenoate per 100 gm body weight per day; phospholipids decreased by 12%. The cholesterol to phospholipid molar ratio increased from 0.419 to 0.555. Membrane fluidity, as measured by the fluorescent probe 1,6‐ diphenyl‐ 1,3,5‐hexatriene decreased after treatment with 20 μmoles canrenoate per 100 gm body weight per day for 3 days.These results describe in vivo and in vitro inhibition of hepatic (Na+,K+)ATPase activity. Increased membrane cholesterol with decreased phospholipid alters membrane fluidity and may be partially responsible for the change in (

ISSN:0270-9139    

DOI:10.1002/hep.1840030403

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY

摘要:

AbstractAn unusual and impressive hyperbilirubinemia was induced in Chinese hamsters by administration of diethylstilbestrol (DES). This icterus was dose‐dependent and affected females more severely than males. However, a similar mortality was detected in both sexes. Another hamster, the Armenian hamster, was even more susceptible to the icteric and lethal effects of DES. The hamster model of DES‐induced icterus showed many clinical dissimilarities when compared to the human estrogen‐induced jaundice, simple cholestatic jaundice. Furthermore, hepatic pathology was distinctly different as canalicular cholestasis was absent although other degenerative and regenerative hepatocellular changes were present. Livers of Armenian hamsters were more severely affected than were livers from Chinese hamsters and contained Mallory bodies even within 1 week after DES treatment. A modest, nonlethal jaundice also was detected in European hamsters after DES injection, whereas Syrian hamsters were not affected even after larger doses. This unique sensitivity to DES, and the spectrum of sensitivity within these related hamsters (Armenian ± Chinese ± European vs. resistant Syrian) provide an interesting model for study of DES effect on hepatic f

ISSN:0270-9139    

DOI:10.1002/hep.1840030404

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY

摘要:

AbstractSinusoidal liver cells were isolated from the livers of 3‐, 12‐, 30‐, and 36‐month‐old female BN/ BiRij rats by enzymatic digestion. The Kupffer cells in the sinusoidal eel suspensions were purified by centrifugal elutriation and kept in maintenance culture for periods of up to about 3 weeks. The viability and yield of Kupffer cells per gram of body weight did not change with the age of the donor rat. The ultrastructural, cytochemical, and functional characteristics of Kupffer cells as observed in perfusion‐fixed liver were retained during several days of maintenance culture. The consistent observation of worm‐like structures in cultured Kupffer cells indicated the reformation of the specific fuzzy coat of the cells during culture. Endogenous peroxidatic and acid phosphatase activities were evident in cultured Kupffer cells and showed the same localization as observed in perfusion‐fixed liver. Kupffer cells in culture were able to endocytose colloidal carbon, latex particles (0.8m̈m), horseradish peroxidase, and endotoxin, indicating the reappearance of different types of specific membrane receptors. The ultrastructural appearance of Kupffer cells was not markedly influenced by the age of the donor rat. However, with increasing age, the lysosomes showed increasing amounts of electron dense lipid‐like material and iron in the form of ferritin. No qualitative age‐related changes in the enzymes tested or in the endocytic capacity of the Kupffer cells were observed. On the basis of these observations, maintenance cultures of purified Kupffer cells can be considered as a valuable model for studying Kupffer cell functions, also in relatio

ISSN:0270-9139    

DOI:10.1002/hep.1840030405

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY

摘要:

AbstractThe serum concentration of 7‐aminobutyric acid (GABA) has been found to be elevated by more than an order of magnitude in a rabbit model of acute hepatic failure. A potential mechanism for increased serum GABA levels in liver failure is decreased catabolism of GABA. To study this possibility, GABA‐transaminase activities were measured in nonneural tissues, and the kinetics of3H‐GABAin vivowere defined in both normal rabbits and rabbits with galactosamine‐induced acute liver failure. Liver failure was associated with 56 and 80% increases in the activities of GABA‐transaminase in liver and kidney, respectively. In the normal rabbit following the intravenous injection of3H‐GABA, total radioactivity in the serum decreased very rapidly initially and much more slowly after 3 to 4 min. Levels of labeled metabolites of3H‐GABA increased very rapidly in serum and reached a plateau after 5 to 10 min. The dependence of total serum radioactivity on time was similar for rabbits 10 hr after galactosamine injection, and control rabbits, with the exception that total serum radioactivity was higher during the first 3 min of the study in galactosamine‐treated rabbits. In rabbits in hepatic coma, total serum radioactivity was higher but radioactivity in metabolites was lower than in controls at corresponding times. Clearance of3H‐GABA from the circulation (i.e., the product of the initial volume of distribution and the fractional catabolic rate, milliliters per minute) was reduced by 26% in rabbits 10 hr after galactosamine injection and by 61% in rabbits in hepatic coma. The reduction in clearance of3H‐GABA was associated with a decrease in the initial volume of distribution but no appreciable change in the fractional catabolic rate of GABA. The magnitude of the decrease in clearance did not fully account for the increase in serum GABA concentrations observed during acute liver failure. These findings suggest that, in addition to impaired GABA metabolism, an increase in the delivery rate of GABA to the circulation occurs in acute hepatic failure. Possible mechanisms for the latter phenomenon include increases in synthesis of GABA from glutamate in the liver and/or kidney, synthesis of GABA by gut bacteria permeability of the intestin

ISSN:0270-9139    

DOI:10.1002/hep.1840030406

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY

摘要:

AbstractThe value of monitoring the serum activity of SGOT, as well as markers of hepatitis B virus and hepatitis A virus infections, in the patients and staff of two dialysis units has been assessed retrospectively. Sera were checked each month for SGOT and HBsAg on 406 patients and 170 staff members over a 4‐year period. Anti‐HBc, anti‐HBs, and anti‐hepatitis A antibodies were assayed on the stored sera. Only 30% of the patients had normal SGOT values (<65 units per ml) on all occasions. Most of the abnormal values were<100 units per ml and could not be explained. Viral hepatitis was a reasonable explanation for only half of those instances where the SGOT value was greater than 100 units per ml. Hepatitis A virus contributed nothing to the problem of dialysis‐associated liver disease. Testing for HBsAg alone missed approximately 40% of the hepatitis B events acquired in the unit. Only two of these episodes were of epidemiologic importance, however, because the rest were recognized only after there was serologic resolution of the infection. There was a high frequency of potentially “false positive” reactions with all the antibodies tested. It is not cost‐effective to monitor dialysis patients and staff regularly with anti‐HBc, anti‐HBs, or antibodies against hepatitis A. Initial screening with anti‐HBc and anti‐HBs on entry to the unit is of value but weak positive results must be interpreted with caution since approximately half of such results will

ISSN:0270-9139    

DOI:10.1002/hep.1840030407

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY

摘要:

AbstractTwenty‐four adult Beechey ground squirrels persistently infected with the hepatitis B virus‐related ground squirrel hepatitis virus (GSHV) remained infected with high levels of viral surface antigen (GSHsAg) and virion‐associated DNA polymerase activity in the blood for over 2 years in captivity. Unlike humans infected with hepatitis B virus, no GSHsAg‐bearing ground squirrels had surface antigen in the blood without DNA polymerase‐containing virions, and the levels of these did not change. Only a very mild hepatitis was observed histologically in some of the virus‐infected animals, with faint Shikata‐staining detectable in some. Other animals exhibited no histologic evidence of hepatitis. While the closely related woodchuck hepatitis virus has been associated with more severe chronic hepatitis and a high incidence of liver cancer in woodchucks, these were not found in GSHV‐infected ground squirrels when a similar number of animals were followed for a similar time of observation. Experimental infection of ground squirrels with no evidence of current or past GSHV infection resulted in three types of response: (i) self‐limited or transient GSHV‐positive infection; (ii) GSHV‐positive infection which became persistent, and (iii) primary anti‐GSHs and anti‐GSHc (antibody to the viral core antigen) responses without detectable GSHsAg or virion DNA polymerase activity in the blood. These responses are similar to those observed following experimental infection of man with HBV. GSHV produced none of the three responses when injected into a variety of laboratory animal species and a chimpanzee, causing only an antibody response to GSHsAg. No evidence of current or past infection was detected in a number of animal species from an area endemic for GSHV. The virus has only been found in one area of northern California, with a carrier rate in t

ISSN:0270-9139    

DOI:10.1002/hep.1840030408

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY

摘要:

AbstractBy routine screening for serologic markers of hepatitis A and B in patients with acute hepatitis, 30 chronic carriers of hepatitis B virus with serologic evidence of acute hepatitis A and two patients with simultaneous acute infection with hepatitis A virus and hepatitis B virus were detected.For evaluation of clinical data, two major risk groups were distinguished. Nine patients were drug addicts and 17 were children and young adults from Mediterranean countries or southeast Asia.During the acute phase of illness, serum bilirubin and SGPT levels did not differ from those in other patients with acute hepatitis A. In three patients for whom follow‐up sera were available, HBsAg concentration decreased during the acute stage of hepatitis

ISSN:0270-9139    

DOI:10.1002/hep.1840030409

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY

摘要:

AbstractThis study reports the findings of an electron microscopic search for so‐called non‐A, non‐B nuclear particles in liver biopsies from patients with mainly chronic or prolonged liver disease and from chimpanzees. In patients without hepatitis B virus or acute hepatitis A virus serological markers, non‐A, non‐B‐like nuclear particles were seen in hepatocytes in 28 of 31 cases of presumed non‐A, non‐B hepatitis, but also in 11 of 12 cases of liver disease not usually attributed to hepatitis viruses. They were also seen in 22 of 24 patients with HBsAg, in 3 of 3 patients with anti‐HBc and no HBsAg, in 1 of 2 patients with hepatitis A, in a case of cytomegalovirus hepatitis, and in 16 of 19 patients whose serology was not available or inconclusive. The particles were present in 1 of 8 untreated HBsAg‐negative chimpanzees and in 2 of 2 HBsAg‐positive chimpanzees. They appeared in 4 of 4 chimpanzees developing non‐A, non‐B hepatitis following exposure to various inocula. Three patterns of particle aggregates were distinguished, all of which had been shown by others in non‐A, non‐B hepatitis. Dense aggregates were predominant, while others have shown intermediate aggregates more often; reasons for this difference could be technical. No pattern was specific for any condition. Either non‐A, non‐B‐like nuclear particles, although associated with non‐A, non‐B hepatitis, are not specific for this condition, or non‐A, non‐B hepatitis viruses are extremel

ISSN:0270-9139    

DOI:10.1002/hep.1840030410

出版商:W.B. Saunders    

年代:1983

数据来源: WILEY