|
1. |
Hepatic Fibrosis After Long‐Term Administration of Ethanol and Moderate Vitamin A Supplementation in the Rat |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 1-11
Maria Anna Leo,
Charles S. Lieber,
Preview
|
PDF (1302KB)
|
|
摘要:
AbstractRats were fed up to 9 months diets supplemented with vitamin A in an amount that, by itself, had no apparent adverse effect on the liver. When associated with chronic ethanol administration, vitamin A supplementation strikingly exacerbated ethanol‐induced abnormalities: fat accumulation was increased and numerous giant mitochondria were observed. Furthermore, lesions appeared which ethanol alone does not produce in rats, namely necrosis, inflammation, and fibrosis. Vitamin A supplementation increased the number of fat storing cells (lipocytes) which positively correlated with vitamin A accumulation in the liver. However, when vitamin A supplementation was combined with ethanol administration, vitamin A levels in the liver and the number of fat storing cells decreased and numerous myofibroblasts appeared in association with abundant collagen fibers. There was also hepatic inflammation and necrosis, accompanied by a rise in serum glutamate dehydrogenase, SGOT, and SGPT and a decrease in retinol binding protein and vitamin A. We conclude that amounts of vitamin A, which by themselves appear harmless, may produce severe liver lesions when associated with chronic ethanol consumptio
ISSN:0270-9139
DOI:10.1002/hep.1840030101
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
2. |
Modulation by S‐Adenosyl‐L‐Methionine of Hepatic Na+, K+‐ATPase, Membrane Fluidity, and Bile Flow in Rats with Ethinyl Estradiol‐Induced Cholestasis |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 12-17
Urs A. Boelsterli,
Gopa Rakhit,
Tibor Balazs,
Preview
|
PDF (675KB)
|
|
摘要:
AbstractStructural and functional changes in the surface membranes of hepatocytes play a pivotal role in the induction and reversion of some forms of drug‐induced cholestasis. To elucidate the mechanism by which S‐adenosyl‐L‐methionine (SAMe) leads to a partial reversion of bile flow impairment caused by ethinyl estradiol (EE), female Sprague‐Dawley rats were given oral doses of EE (5 mg per kg per day, for 3 days) with and without simultaneous administration of SAMe (25 mg per kg, 3 times per day, for 3 days). Na+, K+‐ATPase activity and membrane microviscosity as measured by fluorescent polarization were assayed in isolated liver plasma membranes (LPMs). SAMe administration to normal and EE‐treated rats resulted in a marked increase in Na+, K+‐ATPase activity and LPM fluidity. EE alone did not cause any change in the physicochemical properties of the LPMs. Hepatic Mg2+‐ATPase and y‐glutamyl transpeptidase activities were not affected by SAMe alone but increased when SAMe was given together with EE. These data indicate that the interaction of in vivo administered SAMe with hepatocyte plasmalemma and its effect on lipid fluidity and enzymes of the LPMs showed a high specificity and an inverse relationship between Na+, K+‐ATPase activity and fluorescence polarization values. Furthermore, modulation of hepatic Na+, K+‐ATPase was associated with SAMe‐induced protection against bile flow impairment due to EE; however, it was not the causative factor for EE‐induced cholestasis under the experimental conditions. These findings suggest that changes in surface membrane structure and function might account in part for the reversal by SAMe of EE‐induced impairme
ISSN:0270-9139
DOI:10.1002/hep.1840030102
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
3. |
Biochemical Separation of Na+, K+‐ATPase from a “Purified” Light Density, “Canalicular”‐Enriched Plasma Membrane Fraction from Rat Liver |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 18-28
James L. Boyer,
Rose M. Allen,
Oi Cheng Ng,
Preview
|
PDF (1195KB)
|
|
摘要:
AbstractCytochemical studies suggest that Na+, K+‐ATPase is localized to sinusoidal and lateral portions of the hepatocyte plasma membrane whereas Mg++‐ATPase and alkaline phosphatase are luminal or canalicular membrane markers. To validate further these cytochemical findings, we have isolated from the nuclear pellet of rat liver homogenates a liver plasma membrane (LPM) fraction enriched in all three enzyme markers, as previously described (Biochimica et Biophysica Acta 1975; 401:59–52). Following tight Dounce homogenization, the vesiculated membrane preparation was further separated on a multiple‐step discontinuous sucrose density gradient (d 1.12 to 1.22). Na+, K+‐ATPase activity “dissociated” from Mg++‐ATPase activity, sedimenting at densities of 1.14 and greater. Further studies were carried out in two‐step discontinuous sucrose gradients (1.13 and d ± 1.13), and a light density fraction (d 1.13) was further characterized in calcium‐free media (since addition of calcium increased contamination with intracellular membranes). Electron microscopy demonstrated a homogeneous vesicular membrane population in contrast to the heavy density fraction (d ± 1.13) which contained membrane sheets and junction complexes as well as vesicles. The light density fraction was highly enriched in Mg++‐ATPase (42.1 x homogenate specific activity) and alkaline phosphatase (64.6 X homogenate), 3 to 4 times their activities in the original LPM. In contrast, Na+, K+‐ATPase activity in the light density fraction, diminished 16‐fold from values in the original unfractionated LPM. All but 15% of total Na+, K+‐ATPase activity in the original LPM could be accounted for in unwashed preparations. Neither cholesterol/phospholipid ratios nor an analysis of peptides on sodium dodecyl sulfate gel electrophoresis demonstrated differences in the composition of the light vs. heavy density subfractions, although there were relative increases in several peptide bands in the light density subtraction. These studies provide further supporting biochemical evidence for the concept that Na+, K+‐ATPase resides on different membrane domains than does Mg++‐ATPase and alkaline phosphatase and further characterizes a vesiculated membrane preparation highly enriched in puta
ISSN:0270-9139
DOI:10.1002/hep.1840030103
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
4. |
Decreased Albumin and Increased Fibrinogen Secretion by Single Hepatocytes from Rats with Acute Inflammatory Reaction |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 29-33
Dominique Bernuau,
Edith Rogier,
Gérard Feldmann,
Preview
|
PDF (691KB)
|
|
摘要:
AbstractDuring the acute inflammatory reaction (AIR), the plasma concentration of several plasma proteins, including fibrinogen, is increased as a result of enhanced production by the liver. Whether this increased production influences the production of the other plasma proteins at the single hepatocyte level is not known. Accordingly, we simultaneously measured albumin and fibrinogen secretion by single hepatocytes isolated from normal rats and from rats sacrificed 24 hr after a turpentine‐induced AIR, using an hemolytic plaque test. In normal rats, 74, 82, and 98% of the hepatocytes were detected as secreting albumin, after 1, 2, and 4 hr of incubation, respectively. Simultaneously, 0, 32, and 62% of the hepatocytes were detected as secreting fibrinogen at the same incubation times. For secretion of both proteins, a significant correlation was established between the diameter of a plaque‐forming hepatocyte and its hemolytic plaque. In rats with AIR, the formation of hemolytic plaques detecting albumin secretion was slowed down compared to normal rats, since only 0, 36, and 78% of the hepatocytes were forming hemolytic plaques after 1, 2, and 4 hr of incubation, respectively. Simultaneously, the formation of hemolytic plaques detecting fibrinogen secretion was increased compared to normal rats, since at the same incubation times, 52, 78, and 93% of the hepatocytes formed hemolytic plaques. A significant correlation between the diameter of a plaque‐forming hepatocyte and its hemolytic plaque was still maintained for both protein secretion.These results demonstrate that during the AIR enhanced fibrinogen production is the result of an increased secretion rate per cell, and decreased albumin secretion is the result of a lowered secretion rate per cell, generalized for all hepatocytes. These data strongly suggest that there is a reciprocal modulation of fibrinogen and albumin secretion at the single hepatocyte level during th
ISSN:0270-9139
DOI:10.1002/hep.1840030104
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
5. |
Effect of Chronic Ethanol Feeding on Hepatic Mitochondria in the Monkey |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 34-40
Samuel W. French,
Boris H. Ruebner,
Esteban Mezey,
Tsunenobu Tamura,
Charles H. Halsted,
Preview
|
PDF (874KB)
|
|
摘要:
AbstractThe effect of chronic ethanol feeding on hepatic mitochondrial morphology and histochemically measured succinic dehydrogenase activity was assessed. Five monkeys of the speciesMacaca radiatareceived a nutritionally adequate diet containing 50% of the calories as ethanol, while five others were pair‐fed the same diet except that ethanol was isocalorically substituted by carbohydrate. Liver morphology was assessed at 12 and 24 months and at sacrifice after 40 to 48 months of ethanol feeding. The ethanol‐fed animals developed mild to moderate fatty liver as did some of the controls. No necrosis or fibrosis developed. All ethanol‐fed animals developed centrilobolar mega‐mitochondria and centrilobular “shift” in histochemically assayed succinic dehydrogenase activity characteristic of animals fed ethanol for prolonged periods. These mitochondrial changes persisted throughout the 48‐month test period without progressive increase in severity or accompanying pathology. It is concluded that the morphologic and histochemically assessed mitochondrial changes do not necessarily represent a progressive destructive effe
ISSN:0270-9139
DOI:10.1002/hep.1840030105
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
6. |
Effect of Chronic Ethanol Feeding on Hepatic Collagen in the Monkey |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 41-44
Esteban Mezey,
James J. Potter,
Samuel W. French,
Tsunenobu Tamura,
Charles H. Halsted,
Preview
|
PDF (521KB)
|
|
摘要:
AbstractThe effect of chronic ethanol feeding was determined on parameters of hepatic collagen metabolism in the monkey. Four monkeys of the speciesMacaca radiatareceived a nutritionally adequate diet containing 50% of the calories as ethanol, while four others were pair‐fed a diet in which ethanol was isocalorically substituted by carbohydrate. Liver biopsies were obtained at 3, 12, and 24 months, and the animals were killed between 40 and 48 months after initiation of the diets. The ethanol‐fed animals developed various degrees of fatty infiltration, but no necrosis, inflammation, or fibrosis. The amount and distribution of collagen Types I, III, and IV demonstrated by immuno‐histochemical techniques was not altered after ethanol feeding. No changes were found in hepatic protein‐bound hydroxyproline or in collagen prolyl hydroxylase activity at the various time intervals. Liver free proline and the incorporation of labeled proline into protein‐bound hydroxyproline by liver slices were not altered after 40 to 48 months of ethanol feeding. This study shows that prolonged feeding of ethanol together with an adequate diet results in fatty infiltration but not deposition or alteration of hepatic collagen m
ISSN:0270-9139
DOI:10.1002/hep.1840030106
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
7. |
Effect of (+)‐Cyanidanol‐3 in Acute HAV, HBV, and Non‐A, Non‐B Viral Hepatitis |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 45-49
Marcello Piazza,
Vincenzo Guadagnino,
Ludovico Picciotto,
Renato De Mercato,
Antonio Chirianni,
Raffaele Orlando,
Gerard Golden,
Preview
|
PDF (496KB)
|
|
摘要:
AbstractA double‐blind trial was carried out on 124 randomized patients with acute viral hepatitis, of whom 58 were treated with (+)‐cyanidanol‐3 in a dose of 3 gm per day and 66 with placebo. The treatment was given for 50 days. At 5‐day intervals, SGPT, SGOT, and total serum bilirubin levels were tested. For the total group of patients, the levels of SGPT and SGOT activity were significantly lower in the cyanidanol group than in the control group from 30th to 50th day of treatment (with exception of SGOT at Day 35) (Student's t test: p between 0.01 and 0.05).In 35 patients with acute hepatitis caused by hepatitis A virus, 17 treated with cyanidanol and 18 controls, no significant differences for either SGPT and SGOT were observed. In 58 patients with acute hepatitis caused by hepatitis B virus, 27 treated with cyanidanol and 31 controls, a trend in favor of the cyanidanol group was observed after 30 days of treatment in SGPT activity, the difference being statistically significant after 45 days of treatment (p<0.05). There was also a trend in favor of the cyanidanol group for SGOT activity from the 30th to 45th day of treatment (p between 0.05 and 0.10). In 31 patients with acute hepatitis caused by hepatitis non‐A, non‐B virus, 14 treated and 17 controls, a significant difference between the groups, in favor of the cyanidanol group was observed for both SGPT and SGOT after 40 and 45 days of treatment (p<0.05). The effect of cyanidanol on the transaminases appeared to be a suppression of the “rebounds” occurring from Day 30 onward. There were no significant differences in the evolution of levels of total serum bilirubin.Among the patients with acute hepatitis caused by hepatitis B virus, 10 of the 27 patients treated with cyanidanol became HBsAg negative after 50 days of treatment compared to 16 of 31 in the control group. This difference is not statistically significant. Cyanidanol had no effect on carrier state. Since patients who show rebounds in levels of serum transaminase activity after apparent recovery from the initial phase usually undergo a more prolonged convalescence, it appears that treatment with (+)‐cyanidanol‐3 could be useful in shortening the total duration of their illness. It is essential that the investigations of the effects of drugs in viral hepatitis be performed on well‐defined etiological
ISSN:0270-9139
DOI:10.1002/hep.1840030107
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
8. |
Effect of Inhibitors of Prostaglandin Synthesis On Induced Diuresis in Cirrhosis |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 50-55
Daniel Mirouze,
Robert D. Zipser,
Telfer B. Reynolds,
Preview
|
PDF (613KB)
|
|
摘要:
AbstractThe effect of inhibitors of prostaglandin synthesis on diuretic action was examined in patients with ascites due to chronic liver disease and in normal subjects. In patients with ascites, natriuresis after 80 mg i.v. furosemide was reduced 82% by pretreatment with indomethacin. Creatinine clearance was reduced only 16%. These effects were likely due to inhibition of renal prostaglandin synthesis, since urinary prostaglandin E2 fell and there was also reduction in natriuresis with naproxen (52%). The effects were not specific for furosemide since spironolactone‐induced natriuresis was also reduced by indomethacin (82%), naproxen (52%), and aspirin (33%). In normal subjects, indomethacin reduced furosemide natriuresis by only 14% while creatinine clearance was not affected. The mechanisms of these, drug interactions are uncertain but probably involve renal hemodynamics which appear to be supported importantly by renal prostaglandins in patients with ascites due to liver diseas
ISSN:0270-9139
DOI:10.1002/hep.1840030108
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
9. |
Plasma Norepinephrine, Weak Neurotransmitters, and Renin Activity During Active Tilting in Liver Cirrhosis: Relationship with Cardiovascular Homeostasis and Renal Function |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 56-64
Mauro Bernardi,
Franco Trevisani,
Costanza Santini,
Giorgio Zoli,
Mario Baraldini,
Amedeo Ligabue,
Giovanni Gasbarrini,
Preview
|
PDF (1016KB)
|
|
摘要:
AbstractDerangements in cardiovascular homeostasis are well‐known features of liver failure. To evaluate the role of possible alterations in adrenergic and reninangiotensin systems in this context, tilting‐induced changes in plasma norepinephrine, octopamine, β‐phenylethanolamine, and plasma renin activity were related to modifications in blood pressure, heart rate, plasma volume, and renal function in 10 healthy controls and 20 patients with liver cirrhosis.After 2 hr of bed rest, the patients had higher norepinephrine (p<0.05), octopamine, β‐phenyl‐ethanolamine (p<0.001), plasma renin activity (0.1 ± p ± 0.05), heart rate (p<0.05), and lower mean arterial pressure (0.1 ± p ± 0.05). Renal function was characterized by reduced creatinine clearance and filtered sodium (p<0.001); tubular rejection fraction of sodium and sodium excretion were not significantly reduced. After the change in posture (observation period of 1 hr), tilting‐induced tachycardia was abolished in patients who also showed a significant drop in blood pressure after a transient initial increase at 10 min, whereas a steady state was observed in normal subjects. Norepinephrine and plasma renin activity increases were greater and more prolonged in cirrhotics than in controls; octopamine and β‐phenylethanolamine did not change in the latter and increased in the former, where they correlated with plasma norepinephrine in basal conditions and after tilting (r ± 0.49). Creatinine clearance, filtered sodium, and tubular rejection fraction of sodium underwent a greater decrease in cirrhotics. Although plasma volume reduction was more evident in cirrhotics, it remained steady after 10 min in both groups. In basal conditions and after tilting (60 min), plasma renin activity inversely correlated with arterial pressure (p<0.05) and creatinine clearance (p<0.01) in cirrhotic patients.In conclusion, the adrenergic system, although hyper stimulated, did not achieve an adequate cardiovascular response which could be due, at least in part, to hyperproduction of weak neurotransmitters. The renin‐angiotensin system played a compensatory role and its activation appears to be mainly dependent o
ISSN:0270-9139
DOI:10.1002/hep.1840030109
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
10. |
Hepatitis B Virus Status of Southern African Blacks with Hepatocellular Carcinoma: Comparison Between Rural and Urban Patients |
|
Hepatology,
Volume 3,
Issue 1,
1983,
Page 65-68
Michael C. Kew,
Elizabeth Rossouw,
John Hodkinson,
Alan Paterson,
Geoffrey M. Dusheiko,
J. Whitcutt Michael,
Preview
|
PDF (462KB)
|
|
摘要:
AbstractHepatocellular carcinoma (HCC) is less common and occurs at a much older age in urban than in rural southern African Blacks. These differences may reflect differences in the etiology of the tumor in the two populations. The purpose of this study was to compare the hepatitis B virus (HBV) status of 150 HCC patients who were born and had lived all their lives in a rural environment with 158 patients who were born and brought up in a rural setting but then became urbanized. HBsAg and all markers of present or past HBV infection [HBsAg(+) or anti‐HBc(+) or anti‐HBs] were significantly less common in the urban patients when the two groups were considered as a whole (p<0.001 and p<0.05, respectively). However, because the rural patients were considerably younger (mean age 34.7 years; 66% less than 40 years of age) than the urban patients [mean age 50.9 years (p<0.0005), 19.0% less than 40 years of age (p<0.001)], an age‐related analysis was performed. No significant difference in any HBV marker was found between rural and urban patients. The association between active HBV infection and HCC was similar in young patients, both rural and urban, and the prevalence of HBs antigenemia decreased in both groups with increasing age. We conclude that the differences in incidence and age of onset of HCC in rural and urban southern African Blacks cannot be attributable to differences in HBV s
ISSN:0270-9139
DOI:10.1002/hep.1840030110
出版商:W.B. Saunders
年代:1983
数据来源: WILEY
|
|