bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of capillarization in hepatic failure: Studies in carbon tetrachloride-induced cirrhosis
Authors: Martinez-Hernandez Antonio , Martinez Jose 
Published: March 2007

During the cirrhotic process, the hepatic microvascular phenotype is transformed from sinusoids (discontinuous capillaries) into continuous capillaries. This transformation has been termed capillarization. Many hepatic functions depend on the rapid, bidirectional exchange of macromolecules between plasma and hepatocytes. To determine whether capillarization contributes to hepatic failure in cirrhosis, we decided to study the plasma clearance (125I) and hepatocyte uptake (electron microscopy) of three tracers in normal and cirrhotic rats. The tracers chosen were a hemeundecapeptide with peroxidatic activity (fluidphase pinocytosis), asialofetuin (receptor-mediated endocytosis of a medium size protein) and ferritin (receptor-mediated endocytosis of a large size protein). The results demonstrate a decreased hepatocyte uptake of hemeundecapeptide; a significant delay in plasma clearance of asialofetuin; and a minor delay in plasma clearance of ferritin, but a striking trapping of ferritin in the cirrhotic capillary basement membrane. The delayed plasma clearance in cirrhosis cannot be ascribed to a decreased number of surface receptors because, in isolated hepatocytes, the number of molecules bound per cell was equivalent in normal and cirrhotic livers.
These findings support the concept of capillarization with the formation of continuous diffusion and filtration barriers between plasma and hepatocytes, representing a significant hindrance to the bidirectional macromolecular exchange normally taking place between these two compartments. Furthermore, at least in the case of ferritin, the capiliary basement membrane of cirrhotic livers seems to be the major filtration barrier. This hindrance to hepatocyte uptake, and presumably also to secretion, may be the cause (or at least a major determinant) of the hepatic failure characteristic of cirrhosis. (Hepatology 1991;14: 864-874).
Long-term clinical and histopathological follow-up of chronic posttransfusion hepatitis
Authors: di Bisceglie Adrian M. , Goodman Zachary D. , Ishak Kamal G. , Hoofnagle Jay H. , Melpolder Jacqueline J. , Alter Harvey J. 
Published: March 2007

We have evaluated the clinical and histopathological outcomes of patients who contracted chronic non A, non B hepatitis as a result of transfusions administered during heart surgery at the National Institutes of Health. Posttransfusion hepatitis developed in 65 of 1,070 (6.1%) patients and became chronic in 45 (69%) of those cases. Antibody to hepatitis C virus was detectable in 53 patients (82%) with posttransfusion non A, non B hepatitis. Thirty-three patients with chronic non A, non B hepatitis agreed to liver biopsy (group 1). In addition, six other patients with chronic posttransfusion non A, non B hepatitis were evaluated (group 2). These 39 patients were followed between 1 and 24 yr (mean = 9.7 yr). Cirrhosis developed in 8 patients (20%) between 1.5 and 16 yr after blood transfusion. Of the 33 patients in group 1, 11 (33%) died during follow-up. In two cases (6%), this was related to liver failure. At this writing, two additional patients (6%) have decompensated cirrhosis and one (3%) has debilitating fatigue. Twenty of 33 patients (61%) with histological evidence of chronic active hepatitis or cirrhosis are asymptomatic and have no clinical evidence of liver disease.
Thus chronic non A, non B posttransfusion hepatitis appeared to be due to hepatitis C virus infection in most cases. It was associated with the development of cirrhosis in approximately 20% of cases and end-stage liver disease in 12% of patients followed prospectively. Most patients with histological evidence of cirrhosis or chronic active hepatitis, however, had minimal clinical evidence of liver disease within the time frame of this study. (Hepatology 1991;14:969-974.)
Growth of normal human hepatocytes in primary culture: Effect of hormones and growth factors on DNA synthesis
Authors: Ismail Tariq , Howl John , Wheatley Mark , McMaster Paul , Neuberger James M. , Strain Alastair J. 
Published: March 2007

Although the ability of hormones and growth factors to stimulate DNA synthesis in rat hepatocytes has been investigated extensively, no such study of human hepatocytes has been reported. Here we describe a series of experiments to identify those factors that regulate human hepatocyte DNA synthesis in vitro and which therefore may play a role in the control of human liver regeneration.
Human hepatocytes were isolated from normal liver tissue obtained after graft reduction for transplantation into pediatric recipients. Cells were maintained in culture for up to 5 days, and DNA synthesis was determined. Hydroxyurea reduced [3H]thymidine incorporation into DNA by 95%, indicating replicative DNA synthesis. As previously found with rat hepatocytes, epidermal growth factor and transforming growth factor-α stimulated DNA synthesis at low nanomolar concentrations; transforming growth factor-α was slightly more potent. Although the overall rate of thymidine incorporation was lower than that for rodent cells, human hepatocytes were sensitive to lower concentrations of these growth factors, and the degree of stimulation was similar. Conversely, transforming growth factor-β inhibited DNA synthesis at low picomolar levels. By contrast (unlike rat hepatocytes), arginine-vasopressin failed to initiate or potentiate DNA synthesis in human cells.
These data indicate that normal human hepatocytes can respond to low concentrations of growth promoters or inhibitors, previously shown to have activity on rat hepatocytes. These factors may then play a role in control of human liver growth. However, important species differences are apparent, highlighting the limitations of extrapolating from animal studies to humans. (Hepatology 1991;14:1076-1082.)
Efficacy and safety of ursodeoxycholic acid for dissolution of gallstone fragments: Comparison with the combination of ursodeoxycholic acid and chenodeoxycholic acid
Authors: Sackmann Michael , Pauletzki Juergen , Aydemir Uelker , Holl Joseph , Sauerbruch Tilman , Hasford Joerg , Paumgartner Gustav 
Published: March 2007

A prospective, double-blind, randomized, single-center study was conducted to compare ursodeoxycholic acid alone with the combination of ursodeoxycholic acid and chenodeoxycholic acid for dissolution therapy of gallstone fragments after shock wave lithotripsy. Patients with single radiolucent gallstones up to 30 mm in diameter or up to three stones of similar total volume received either 750 mg ursodeoxycholic acid alone (group A, n = 138) or the combination of 500 mg ursodeoxycholic acid and 500 mg chenodeoxycholic acid (group B, n = 144) in a single bedtime dose. The bile acids were administered from 2 wk before electrohydraulic lithotripsy until 3 mo beyond complete disappearance of all fragments. Patient’s characteristics, stones (group A, 82% single stones, maximum diameter 19 ± 5 mm, mean ± S.D.; group B, 82% single stones, 18 ± 5 mm), lithotripsy treatment and follow-up period were not different between the two groups.
Between the two groups, no statistically significant difference was found in the time required for complete clearance of the fragments (group A, median time = 15 mo; group B, median time = 13 mo; p = 0.7). At 12 mo after lithotripsy, the probability of complete clearance was 46% ± 5% in group A and 49% ± 5% in group B. Diarrhea occurred significantly more often in group B than in group A (p < 0.001) and was the main reason for withdrawal of randomized medication. Severe adverse effects of the bile acids were not observed.
It is concluded that monotherapy with ursodeoxycholic acid is as efficient as the combination of ursodeoxycholic acid and chenodeoxycholic acid for fragment dissolution after lithotripsy. Therapy with ursodeoxycholic acid alone causes diarrhea less frequently and has to be withdrawn less often than the combination of ursodeoxycholic and chenodeoxycholic acid. (Hepatology 1991;14:1136-1141.)
Effects of ritanserin, a selective and specific S2-serotonergic antagonist, on portal pressure and splanchnic hemodynamics in portal hypertensive rats
Authors: Nevens Frederik , Pizcueta Pilar M. , Fernández Mercedes , Bosch Jaime , Rodés Joan 
Published: March 2007

Serotonergic mechanisms have recently been implicated in the pathogenesis of portal hypertension; this suggests that blockade of serotonin S2 receptors may be a new approach for the pharmacological therapy of portal hypertension.
This study was aimed at investigating the effects of ritanserin, a selective S2-serotonergic antagonist, in portal-hypertensive rats whose condition was due to partial portal vein ligation. The animals were randomized under double-blind conditions into two groups: the first received ritanserin (0.7 mg/kg body wt, intravenously), and the second received the same volume of placebo (isotonic saline solution). The hemodynamic studies were performed using radiolabeled microspheres 60 min after drug administration.
Ritanserin administration significantly reduced portal pressure (from 11.8 ± 0.8 mm Hg to 9.4 ± 0.6 mm Hg; p < 0.05). This was associated with lower portocollateral resistance (1.8 ± 0.2 mm Hg/ml/min 100 gm in the ritanserin group vs. 2.3 ± 0.2 mm Hg/ml/min 100 gm in rats receiving placebo; not significant), but we saw no changes in portal-vein inflow (5.5 ± 0.7 ml/min 100 gm vs. 5.4 ± 0.5 ml/min 100 gm), mean arterial pressure (95.9 ± 3.5 mm Hg vs. 94.0 ± 4.0 mm Hg) and cardiac index (31.9 ± 3.5 ml/min 100 gm vs. 28.5 ± 2.6 ml/min 100 gm). Hepatic arterial and kidney blood flows were not modified by ritanserin.
In summary, our results demonstrate that ritanserin infusion decreases portal pressure without causing systemic hemodynamic changes. This effect is probably due to a decrease in portocollateral resistance in portal-hypertensive rats.
These results provide further for a role of serotonin in the pathogenesis of portal hypertension. (Hepatology 1991;14:1174-1178.)
Demonstration of hepatitis B virus DNA by polymerase chain reaction in the serum and the liver after spontaneous or therapeutically induced HBeAg to anti-HBe or HBsAg to Anti-HBs seroconversion in patients with chronic hepatitis B
Authors: Loriot Marie-Anne , Marcellin Patrick , Bismuth Eric , Martinot-Peignoux Michèle , Boyer Nathalie , Degott Claude , Erlinger Serge , Benhamou Jean-Pierre 
Published: March 2007

The objective was to determine the proportion of patients with chronic hepatitis B in whom hepatitis B virus DNA is demonstrated by polymerase chain reaction after HBeAg to anti-HBe or HBsAg to anti-HBs spontaneous or therapeutically induced seroconversion.
Polymerase chain reaction was performed on serum 6 and 12 mo after HBeAg to anti-HBe seroconversion in 12 patients and 2, 6 and 12 mo after HBsAg to anti-HBs seroconversion in 13 patients. Polymerase chain reaction was performed on liver tissue after HBeAg to anti-HBe seroconversion in five patients and after HBsAg to anti-HBs seroconversion in one patient.
Serum HBV DNA was demonstrated by polymerase chain reaction in 83% of patients 6 or 12 mo after HBeAg to anti-HBe seroconversion and in 58%, 31% and 15% of patients at 2, 6 and 12 mo, respectively, after HEsAg to anti-HBs seroconversion. Liver HBV DNA was demonstrated by polymerase chain reaction in all patients tested.
Our results show that (a) a reduced level of hepatitis B virus replication persists in most of the patients after HBeAg to anti-HBe seroconversion and might be predictive of reactivation, and (b) in contrast, hepatitis B virus replication progressively disappears in most of the patients after HBsAg to anti-HBs seroconversion. (Hepatology 1992;15:32-36).
Viability and primary culture of rat hepatocytes after hypothermic preservation: The superiority of the leibovitz medium over the university of wisconsin solution for cold storage
Authors: Poullain Marie-gwenaëlle , Fautrel Alain , Guyomard Claire , Chesne Christophe , Grislain Luc , Guillouzo André 
Published: March 2007

Hepatocytes isolated from adult rat livers were hypothermically preserved for 24 or 48 hr before being plated under conventional culture conditions. They were stored either in the Leibovitz medium, a cell culture medium with and without polyethylene glycol (PEG), a compound known to suppress ischemia-induced cell swelling, or in the University of Wisconsin solution, the most effective solution for cold organ preservation. After 24 or 48 hr of storage at 4.5° C in Leibovitz medium, cell viability and adherence efficiency to plastic dish, were only slightly reduced, whereas University of Wisconsin hepatocytes had a decreased viability and (especially after 48-hr storage) lost their adhesion ability; they did not survive in vitro. The metabolic competence of hepatocytes maintained in Leibovitz medium was retained over the 3 days of culture, as shown by low extracellular levels of the membrane-bound and cytosolic hepatic enzymes, as well as by intracellular glutathione content, albumin secretion rate and several phase I and phase II drug metabolic reactions very close to those found with fresh hepatocytes maintained under similar culture conditions. Addition of polyethylene glycol to the Leibovitz medium resulted in slightly higher viability and function of hepatocytes after cold storage.
These results clearly demonstrate that viability of a transplanted liver does not correlate with long-term in vitro viability of isolated hepatocytes after hypothermic preservation in University of Wisconsin solution. They also suggest that nutritional and energy substrates as found in the Leibovitz medium are probably required to define a suitable solution for cold preservation of isolated parenchymal cells. The findings with Leibovitz medium favor the conclusion that hypothermically preserved hepatocytes could be used for various metabolic studies and for the treatment of liver insufficiency. (Hepatology 1992;15:97-106).
S -adenosylmethionine protects against acetaminophen hepatotoxicity in two mouse models
Authors: Bray Gary P. , Tredger Michael J. , Williams Roger 
Published: March 2007

Because S-adenosylmethionine promotes synthesis of hepatic glutathione in chronic liver disease and is well tolerated in man, we investigated its use as an antidote to acetaminophen hepatotoxicity in two mouse models.
In C57B16 mice, deaths were abolished by S-adenosylmethionine given within 1 hr of 3.3 mmol/kg body wt acetaminophen (0 of 32 vs. 13 of 49, p < 0.005) and reduced if given 2 to 5 hours after acetaminophen administration (4 of 42 vs. 13 of 49, p < 0.01). Mixed disulfate/tosylate salt of S-adenosylmethionine abolished mortality in C3H mice given 2 mmol/kg body wt acetaminophen (0 of 24 vs. 4 of 18; p < 0.05). In both mouse models, S-adenosylmethionine reduced depletion of plasma (median = 20.8 μmol/L vs. 14.6 μmol/L) and liver glutathione (198% vs. 100%; p < 0.05), liver damage and release of AST after acetaminophen administration. Pretreatment with buthionine sulfoximine, which inhibits glutathione synthesis, abolished the beneficial effect of S-adenosylmethionine on survival and plasma glutathione level.

S-adenosylmethionine reduces acetaminophen hepatotoxicity by metabolism of the active moiety to glutathione. This benefit may last as long as 5 hr after acetaminophen ingestion. (Hepatology 1992;15:297-301).
Prophylactic β-blocker therapy: Clinical implications of an aggregate analysis
Authors: Gumucio Jorge J. , Imperiale Thomas F. , McCullough Arthur J. 
Published: March 2007

Background.
The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported.

Methods.
In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo.

Results.
After two years, the mean (± SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 ± 3 percent in the beta-adrenergic-antagonist treatment group and 65 ± 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 ± 2 percent in the treatment group and 82 ± 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 ± 3 percent in the treatment group and 68 ± 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 ± 3 percent in the treatment group and 53 ± 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P < 0.001) and death (P < 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P < 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices.

Conclusions.
Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity.
Pulmonary dysfunction in advanced liver disease
Authors: Kim Sucha 
Published: March 2007

PURPOSE: Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation.
PATIENTS AND METHODS: We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations.
Metabolic and hemodynamic responses of bivascularly perfused rat liver to nerve stimulation, noradrenaline, acetylcholine and glucagon in thioacetamide-induced micronodular cirrhosis
Authors: Zimmermann Thomas , Gardemann Andreas , Machnik Georg , Dargel Rolf , Jungermann Kurt 
Published: March 2007

Thioacetamide-induced rat cirrhosis was characterized by single-cell necroses, fibrosis, nodular parenchyma, decrease in parenchymal volume density and an increase in liver weight per body weight so that the total amount of parenchyma was not altered. The glycogen content was normal, and signs of decompensation were not found.
Isolated livers were single-pass perfused by way of both the hepatic artery and the portal vein. In the normal livers stimulation of the nerve plexuses around the hepatic artery or portal vein (7.5 Hz; 2 msec) and infusions of noradrenaline (1 μmol/L) by way of either vessel and of acetylcholine (10 μmoI/L) by way of the artery only increased glucose output, reduced both portal and arterial flow and increased the intravascular pressures. Glucagon (0.5 nmol/L) augmented glucose release and had no hemodynamic effects. In chronically thioacetamide-injured livers all stimuli caused smaller metabolic alterations per gram of liver weight and decreased portal flow more and arterial flow less with stronger enhancements of intravascular pressures than in the controls.
The lowered metabolic responsiveness per gram of cirrhotic liver was largely compensated by the increase in liver weight. Thus despite massive histological alterations and pronounced increases in stimulation-dependent resistances-predominantly in the portal system-cirrhotic rat livers responded in their glucose metabolism to nervous and hormonal stimuli in almost the same manner as normal livers. (Hepatology 1992;15:464-470).
Inhibition by noradrenaline and adrenaline of the increase in glucose and lactate output and decrease in flow after sympathetic nerve stimulation in perfused rat liver: Possible involvement of protein kinase C
Authors: Miura Hisayuki , Gardemann Andreas , Rosa Josip , Jungermann Kurt 
Published: March 2007

In perfused rat liver stimulation of the hepatic nerve plexuses increased via α1-receptors glucose and lactate output decreased flow and caused an overflow of noradrenaline into the hepatic vein. Infusion of noradrenaline and adrenaline also elicited similar metabolic and hemodynamic alterations via α1-receptors, whereas infusion of isoproterenol via β2-receptors enhanced glucose output and slightly reduced lactate release without affecting flow. The influence of circulating catecholamines on the nerve stimulationdependent changes was investigated.
Noradrenaline (100 nmol/L) or adrenaline (40 nmol/L) but not isoproterenol (1 μmol/L), which themselves caused about half-maximal alterations, strongly inhibited the nerve stimulation-induced increase in glucose and lactate output and decrease in flow but had no effect on noradrenaline overflow.
The protein kinase C activator (4β)phorbol 12-myristate, 13-acetate (100 nmol/L) but not its analog (4α)phorbol 12,13-didecanoate (100 nmol/L) strongly inhibited the metabolic and hemodynamic changes caused by nerve stimulation or noradrenaline infusion. The protein kinase C inhibitor H7 (20 μmol/L) partially prevented the inhibition of the nerve actions by noradrenaline.
The results lead us to conclude that noradrenaline and adrenaline inhibited the metabolic and hemodynamic nerve actions by means of a mechanism involving protein kinase C rather than presynaptic α-receptors or β-receptors. The catecholamines apparently increased via α1-receptors inositol 1,4,5-trisphosphate, which in turn enhanced cytosolic Ca2+ and thus altered metabolism and in part hemodynamics, and diacylglycerol, which in turn activated protein kinase C and thus feedback inhibited the signal chain from α1-receptors via G proteins to phospholipase C. (Hepatology 1992;15:477-484).
A Randomized Controlled Trial of Lymphoblastoid Interferon–α in Patients With Chronic Hepatitis B Lacking Hbeag
Authors: Fattovich Giovanna , Farci Patrizia , Rugge Massimo , Brollo Lucio , Mandas Antonella , Pontisso Patrizia , Giustina Giuliano , Lai Eliana M. , Belussi Fabio , Busatto Graziella , Balestrieri Angelo , Ruol Arturo , Alberti Alfredo 
Published: March 2007

Ongoing hepatitis B virus replication in the presence of antibody to HBeAg can be observed in patients with active liver disease. These forms of chronic hepatitis B have been described as having a poor prognosis. We have conducted a randomized controlled trial to assess the efficacy of lymphoblastoid interferon–α in 60 patients with antibody to HBeAg and hepatitis B virus DNA-positive chronic hepatitis. Patients received 5 million U/m2 interferon three times a week for 6 mo, or no treatment. Final evaluation 18 mo after randomization showed hepatitis B virus DNA negativity and ALT normalization in 53% of treated patients and in 17% of controls (p < 0.01). The probability of sustained hepatitis B virus DNA loss was significantly higher in treated patients than in controls (p < 0.005). Blinded histological assessment revealed improvement in 50% of treated patients compared with 33% of controls. Pretreatment hepatitis B virus DNA and aminotransferase levels and histological appearance were not predictive of response.
The results of this trial indicated that marked reduction of viral replication in serum and remission of liver damage can be obtained with lymphoblastoid interferon in about 50% of patients with HBeAg antibody- and HBV DNA-positive chronic hepatitis. This rate of response is higher than that reported previously. (Hepatology 1992;15:584-589).