bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endotoxin levels measured by a chromogenic assay in portal, hepatic and peripheral venous blood in patients with cirrhosis
Authors: Lumsden Alan B. , Henderson Michael J. , Kutner Michael H. 
Published: March 2007

Endotoxin concentrations were measured in the portal, hepatic and peripheral venous blood of two groups of patients with cirrhosis using a limulus-based chromogenic assay. The high sensitivity of chromogenic detection allowed measurement of endotoxin as low as 10 to 15 pg per ml, an order of magnitude greater than previously possible by gelation studies. Group 1 consisted of 56 patients with cirrhosis undergoing angiographic evaluation. In this group, there was wide variability in hepatic venous concentration [ 73 ± 110 pg per ml (mean ± S.D.)] and peripheral venous concentration [31 ± 58 pg per ml]. However, paired t test showed peripheral venous concentration was significantly (p < 0.001) lower than hepatic venous concentration. Neither hepatic or peripheral venous endotoxin levels correlated significantly with a variety of clinical, biochemical or radiological parameters. Group 2 consisted of 21 patients with cirrhosis undergoing shunt surgery. Endotoxin levels again showed a wide range, with portal venous concentration (142 ± 167 pg per ml) and simultaneous peripheral venous concentration (82 ± 150 pg per ml). Paired t test in this group showed a significant (p < 0.001) portal to peripheral venous gradient.
This study showed the feasibility of measuring endotoxin in plasma to low concentrations by a chromogenic assay technique. It supports the concept of relatively high levels of endotoxin in the portal circulation. In the presence of liver disease, systemic endotoxemia occurs, which is augmented by stressful situations.
Reduction by prostacyclin of acetaminophen-induced liver toxicity in the mouse
Authors: Guarner Francisco , Boughton-Smith Nigel K. , Blackwell Geoffrey J. , Moncada Salvador 
Published: March 2007

The effect of prostacyclin on acetaminophen-induced liver injury has been investigated in the mouse. Two structurally unrelated thromboxane synthetase inhibitors, OKY 1581 and benzyl imidazole, were also examined in order to investigate the role of the prostacyclin-thromboxane balance in the development of hepatic lesions.
Whereas prostacyclin or OKY 1581 given shortly after acetaminophen prevented mortality and reduced liver necrosis, as assessed by serum ALT activity and histology, benzyl imidazole was only effective if given prior to acetaminophen.
Acetaminophen overdose resulted in an enhanced prostaglandin and thromboxane generation by liver homogenates. While OKY 1581 inhibited thromboxane production by the liver homogenates, prostacylcin synthesis was increased. Pretreatment with the cyclooxygenase inhibitor indomethacin blocked both the increase in prostacyclin generation and the protective effect of OKY 1581. Benzyl imidazole inhibited the synthesis of thromboxane but did not enhance prostacyclin production. In addition, the protective effect of benzyl imidazole was unaltered by indomethacin pretreatment. Furthermore, whereas benzyl imidazole interfered with hepatic drug metabolism, as assessed by prolongation of the pentobarbitone sleeping time, prostacylcin and OKY 1581 were without activity.
Prostacyclin treatment can prevent acetaminophen-induced liver necrosis in mice. Enhanced prostacyclin synthesis by the selective thromboxane synthetase inhibitor OKY 1581 also exerts a protective role in this model.
Diabetes-Induced cholestasis in the rat: Possible role of hyperglycemia and hypoinsulinemia
Authors: Garcia-Marin Jose Juan , Villanueva Gloria R. , Esteller Alejandro 
Published: March 2007

In one of our earlier studies, an impaired biliary function in diabetes was suggested. We studied bile formation in rats with streptozotocin-induced diabetes (60 mg per kg body weight). Diabetic rats showed hyperglycemia and hypoinsulinemia, but no significant changes in hematocrit, plasma protein concentration or plasma osmolality. Bile flow was significantly (p < 0.05) reduced (-23%) as compared with control animals, despite a higher (p < 0.05) bile acid secretion rate (+56%).
The biliary responses to three choleretic compounds (taurocholate, ursodeoxycholate and insulin), acting in a very different way upon bile formation, were not impaired in diabetes. The study of the relationship between bile acid output and bile flow, after infusion of taurocholate at different doses (0.25 to 1.5 μmoles per min per 100 gm body weight) showed that diabetesinduced cholestasis in the rat is mainly related to a decreased bile acid-independent fraction of the bile flow.
We tested the possible role of hyperglycemia and hypoinsulinemia as cholestatic factors in diabetes. Glucose infusion [300 mM, 150 μ per min (Group G)] induced a significant (p < 0.05) reduction in bile flow (−0.33 μl per min per gm liver) as compared to the basal period. After acute pancreatectomy (P) or mannoheptulose treatment [0.14 mmole per 100 gm body weight (Group M)], similar cholestatic effects were observed (−0.29 and −0.27 μl per min per gm liver, respectively). However, plasma glucose and insulin concentrations were higher (p < 0.01) in Group G than in P or M.
Glucose infusion to acutely pancreatectomized (PG) or mannoheptulose-treated (MG) rats induced a similar and marked cholestasis (−0.46 and −0.51 μl per min per gm liver, respectively; both p < 0.001). The plasma insulin concentration was not different among the P, M, PG and MG. Nevertheless, a lower (p < 0.05) bile flow was observed in PG and MG, as compared to P and M, respectively. Plasma glucose concentrations were higher (p < 0.001) in PG and MG as compared to P and M.
Bile acid output and plasma osmolality were not significantly different in controls, P, M, PG and MG.
In summary, our results indicate that diabetes induces cholestasis in the rat. They suggest that the decrease in bile formation is not due to general damage to the hepatic secretory system but rather to the presence of additive cholestatic factors, such as hyperglycemia and hypoinsulinemia, which specifically reduce the bile acid-independent fraction of bile flow.
Prospective study of asymptomatic hbsag carrier children infected in the perinatal period: Clinical and liver histologic studies
Authors: Chang Mei-Hwei , Hwang Lu-Yu , Hsu Hey-Chi , Lee Chin-Yun , Beasley Palmer R. 
Published: March 2007

Liver histologic findings were studied in 18 children who were 4 to 9 years old, and who had been HBsAg carriers since having been infected by their mothers in the perinatal period. All were born to HBeAg-HBsAg carrier mothers; the children were followed periodically from birth. Throughout their entire course, none developed symptoms or signs suggestive of liver disease.
All of the 18 children showed mild but definite liver histologic changes: 15 had nonspecific histologic changes, and three had chronic persistent hepatitis. In 13 of 18 children, follow-up aminotransferase activities were abnormal, but none exceeded 100 KU. At the time of biopsy, ALTs on four children were above the upper limit of normal. All children were HBeAg-positive in early infancy, but five lost this antigen and developed antibody during follow-up. The histologic findings in HBeAg-positive children did not differ from those in children with antibody. Perinatal hepatitis B virus infection has been thought to play an important role in chronic liver disease, including hepatocellular carcinoma. This study indicates that some pathologic changes following perinatal infection begin very early.
Selenium deficiency in search of a disease
Authors: Burk Raymond F. 
Published: March 2007

Serum selenium concentrations were found to be significantly lower in women with intrahepatic cholestasis of pregnancy than in women with normal pregnancies during the last trimester of pregnancy and post partum. The activity of the seleno-enzyme glutathione peroxidase had a significant positive correlation with selenium concentration and it was also significantly lower in women with the disease.
These findings suggest that selenium deficiency and reduced glutathione peroxidase activity are associated with the aetiopathogenesis of intrahepatic cholestasis of pregnancy.
Ectopic soft tissue calcium deposition following liver transplantation
Authors: Munoz Santiago J. , Nagelberg Steven B. , Green Paul J. , Angstadt John D. , Yang Shuin L. , Jarrell Bruce E. , Maddrey Willis C. 
Published: March 2007

We observed ectopic soft tissue calcification affecting seven patients following orthotopic liver transplantation. The cause of such calcification is unknown, but potential pathogenetic factors include hyperparathyroidism, calcium administered during and following surgery, renal failure, acid-base changes and citrate in fresh frozen plasma. To investigate some of the mechanisms underlying ectopic calcification following liver transplantation, we determined preoperative levels of ionized serum calcium, phosphate, magnesium, parathyroid hormone (midmolecule assay) and 1,25-(OH)2 vitamin D in 20 patients who underwent 24 liver transplants. In addition, these parameters were measured weekly in 15 patients during the first month after liver transplantation.
Preoperatively, 5 of the 20 patients had elevated serum levels of parathyroid hormone, and 9 others had low levels of 1,25-(OH)2 vitamin D. After liver transplantation, ectopic calcification was found in seven patients (47%). The organs affected in order of frequency were lungs, liver graft, colon, vascular walls, kidneys, adrenal glands and gastric mucosa. One patient with ectopic calcification of both lungs had markedly restricted pulmonary function as well as radiologic evidence of osteopenia and pathologic fractures of three vertebrae. Postoperatively, increased parathyroid hormone levels were found in all patients who developed soft tissue calcification. Parathyroid hormone levels peaked during the second week after transplantation and were higher at all times compared to subjects without calcification. Five of the seven patients with ectopic calcification had associated renal failure. Individuals who developed calcification had received significantly more fresh frozen plasma, red blood cells and elemental calcium postoperatively, but showed no difference in serum levels of calcium, magnesium, vitamin D, total plasma CO2 or phosphate levels when compared to patients without calcification.
We conclude that multiorgan ectopic soft tissue calcification may complicate the postoperative course following liver transplantation. In one patient, calcifications were associated with respiratory insufficiency and bone fractures. Renal failure, secondary hyperparathyroidism and large amounts of transfused blood-derived products appear to be major factors associated with ectopic calcification. We speculate that renal failure and the citrate contained in massive fresh frozen plasma transfusions lead to transient hypocalcemia, which in turn stimulates parathyroid hormone secretion and secondary hyperparathyroidism. Under these conditions, local tissue injury and concomitant administration of exogenous calcium may result in soft tissue calcium deposition.
Interaction of woodchuck hepatitis virus surface antigen with hepatocyte plasma membrane in woodchuck chronic hepatitis
Authors: Michalak Tomasz I. , Churchill Norma D. 
Published: March 2007

The extent of association between woodchuck hepatitis virus surface antigen and host hepatocyte plasma membrane in chronic hepatitis was studied. Purified membranes containing the antigen were treated with various agents which perturb plasma membrane constituents to elute woodchuck hepatitis virus surface antigen. The products from disrupted membranes were analyzed by sedimentation in sucrose gradients and tested to identify the antigen reactivity.
The results indicated that membrane-bound wood-cauck hepatitis virus surface antigen was partially released by 4M potassium chloride, potassium thiocyanate and guanidine, 6M urea or 0.1 N sodium hydroxide (pH 13.5), but not in the presence of low concentrations of these reagents or by 10% 2-mercaptoethanol and 1% sodium dodecyl sulfate. No more than 15% of the total membrane-associated woodchuck hepatitis virus surface antigen was eluted by 0.1 N NaOH, which was found to be the most effective eluent among tested agents at the antigen removal. The remaining woodchuck hepatitis virus surface antigen was resistant to further extraction with sodium hydroxide, as expected for an integral membrane protein. Treatment of the infected membranes with 1% Triton X-100 or 50 mM deoxy-cholic acid, that solubilize the membrane lipid bilayer releasing most of the integral membrane proteins, resulted in the sedimentation of almost all detectable woodchuck hepatitis virus surface antigen reactivity with the detergent-insoluble membrane residues, suggesting a firm interaction of the antigen with the plasma membrane matrix. Partition of the membrane peripheral and integral proteins in 1% Triton X-114 into hy-drophilic and hydrophobic protein fractions, respectively, provided additional evidence that most of the detectable woodchuck hepatitis virus surface antigen reactivity within the infected membranes was associated with their integral proteins.
The results demonstrate that woodchuck hepatitis virus surface antigen found in hepatocyte plasma membrane behaves as a peripheral and an integral membrane protein. It was shown that most of the woodchuck hepatitis virus surface antigen behaving as an integral membrane protein interacts extremely extensively with the membrane. This unexpectedly strong membrane binding of woodchuck hepatitis virus surface antigen may be irreversible in naturally occurring conditions and could be eliminated only by lysis of infected hepatocyte membranes. Viral envelope material firmly associated with hepatocyte plasma membrane may constitute an important element of a complex mechanism leading to persistence of the virus infection that could also be responsible for preservation of hepatocytes with integrated viral genome.
Ventricular function in cirrhosis and portasystemic shunt: A two-dimensional echocardiographic study
Authors: Keller Helmut , Bezjak Vera , Stegaru Beatrice , Buss Jan , Holm Eggert , Heene Dieter L. 
Published: March 2007

Cardiovascular alterations such as increased heart rate, high cardiac output, reduced systemic vascular resistance, and in most of the cases, increased contractility parameters have been recognized in patients with advanced liver disease.
Some investigators define a cirrhotic cardiomyopathy as a hyperdynamic failure of the heart. Consequently, in patients with cirrhosis, the risk of developing further circulatory deterioration may be increased in situations which stress the cardiovascular system. After opening a portocaval shunt, it is expected that a large amount of blood will be distributed from the splanchnic to the pulmonary circulation and put a strain on the heart.
This two-dimensional echocardiographic study was made in 30 patients with cirrhosis and in 20 patients who were chronically treated (range: 16 to 156 months) with portasystemic shunt for prevention of hemorrhage from esophageal variceal bleeding. Patients with portasystemic shunts revealed a change in hemodynamic pattern. There was a significant increase in the left ventricular end-diastolic volume index and also a slight increase in the left ventricular end-systolic index. Cardiac output remained high despite a significant decrease in heart rate due to an elevated left ventricular stroke volume index.
The parameters of systolic ventricular performance were normal.
In contrast to the acute opening of the portacaval shunt, the chronic shunt volume put no strain of clinical significance on the heart.
Regulation of bile acid synthesis. II. Effect of bile acid feeding on enzymes regulating hepatic cholesterol and bile acid synthesis in the rat
Authors: Heuman Douglas M. , Vlahcevic Reno Z. , Bailey Marsha L. , Hylemon Phillip B. 
Published: March 2007

Bile acid synthesis is believed to be regulated by bile salts returning to the liver via the portal vein and suppressing cholesterol 7α-hydroxylase, the rate-limiting enzyme in the bile acid biosynthesis pathway. In order to characterize the relative effectiveness of bile salts in regulating bile acid synthesis, seven different bile acids were administered (1% w/w in chow) to rats over a 14-day period. Biliary bile salt composition was determined from bile samples obtained prior to killing; in all cases, the fed bile acid became the predominant bile salt in bile. The specific activities of microsomal cholesterol 7α-hydroxylase, HMG-CoA reductase and acylcoenzyme A:cholesterol acyltransferase were determined after killing.
Hydrophilic bile salts (ursocholic, hyocholic, ursodeoxycholic and hyodeoxycholic) did not inhibit HMG-CoA reductase or cholesterol 7α-hydroxylase activities. By contrast, more hydrophobic bile salts (cholic, chenodeoxycholic and deoxycholic) inhibited the activities of these two enzymes in order of increasing hydrophobicity. Neither hydrophobic nor hydrophilic bile salts inhibited acylcoenzyme A:cholesterol acyltransferase activity. No consistent effect of bile acid feeding on total microsomal cholesterol was observed.
Based on the results of these studies, we propose that the hydrophilic-hydrophobic balance of the bile acid pool may play an important role in the regulation of bile acid synthesis. We postulate that the activities of cholesterol 7α-hydroxylase and HMG-CoA reductase may be regulated by hydrophobic bile acid-induced changes in the lipid composition and physicochemical properties (fluidity) of the microsomal membranes to which both of these rate-limiting enzymes are attached. Alternatively, hydrophobic bile salts by increasing biliary cholesterol secretion and suppressing HMG-CoA reductase activity may reduce the availability of cholesterol substrate for bile acid synthesis.
Serum vitamin A deficiency and increased intrahepatic expression of cytokeratin antigen in alcoholic liver disease
Authors: Ray Mukunda B. , Mendenhall Charles L. , French Samuel W. , Gartside Peter S. 
Published: March 2007

The clinical and histologic significance of cytokeratin antigen expression in various intrahepatic locations was assessed in 57 patients with alcoholic liver disease as part of a large Veterans Administration Cooperative Study of Alcoholic Hepatitis. Cytokeratin antigen was demonstrated in fixed, paraffin-embedded liver tissue by an avidin-biotin peroxidase method using a mixture of two different monoclonal antibodies, AE1 (acidic; 48, 50 and 56.5 kD) and AE3 (basic; 52, 56, 58 and 65 to 67 kD). In contrast to the normal liver, in which only bile duct epithelium was positive, this antibody mixture stained both bile ducts and hepatocytes in pathologic livers.
Serum levels of vitamin A showed a significant inverse correlation with the amount of cytokeratin antigen (scale: 0 to 3) in hepatocytes without Mallory bodies (p = 0.001), in Mallory body-containing hepatocytes (p < 0.0001) and in bile ducts (p = 0.0074). Increased amount of cytokeratin antigen in each of these locations, in turn, correlated directly with the histologic severity of the liver disease. Histologic severity (fibrosis, parenchymal degeneration/necrosis, hepatocyte regeneration and inflammation) was significantly higher in patients when either Mallory bodies (p < 0.0001) or cytokeratin antigen (p = 0.0021) was present in hepatocytes. Demonstration of cytokeratin antigen in hepatocytes which contained Mallory bodies correlated positively (p = 0.03) with clinical severity of the liver disease as determined by high serum bilirubin and prolonged prothrombin time (Maddrey’s discriminant function). This study suggests that (i) vitamin A deficiency may be a triggering factor in aggregation of cytokeratin filaments, and (ii) the degree of aggregation of cytokeratin may determine the histologic severity and thereby the prognosis of patients with alcoholic liver disease.
Inhibition of the mitochondrial oxidation of fatty acids by tetracycline in mice and in man: Possible role in microvesicular steatosis induced by this antibiotic
Authors: Fréneaux Eric , Labbe Gilles , Letteron Philippe , Dinh The Le , Degott Claude , Genève Jean , Larrey Dominique , Pessayre Dominique 
Published: March 2007

Intravenous administration of high doses of tetracycline may produce severe microvesicular steatosis of the liver in man. A similar disease is observed after ingestion of drugs which inhibit hepatic mitochondrial fatty acid β-oxidation and in subjects with various inborn defects in this metabolic pathway. We therefore determined the effects of tetracycline on the mitochondrial oxidation of fatty acids in mice and in man.

In vitro, addition of tetracycline 0.25, 0.5, 1 or 2 mM inhibited by 15, 38, 56 and 65%, respectively, the formation of β-oxidation products during incubation of palmitic acid with mouse liver mitochondria and the various cofactors necessary for β-oxidation. Inhibition was reversible. Inhibition appeared even greater with human liver mitochondria.
Tricarboxylic acid cycle activity, assessed by the in vitro formation of [14C]CO2 from [1-14C]acetylcoenzyme A by mouse liver mitochondria, was inhibited by 25, 32 and 43%, respectively, in the presence of 0.5, 1 or 2 mM of tetracycline.

In vivo, administration of tetracycline, 0.25 or 1 mmole per kg, inhibited by 53 and 84%, respectively, the exhalation of [14C]CO2 during the first 3 hours following the administration of a tracer dose of [U-14C] palmitic acid. Administration of tetracycline, 0.0625, 0.25 or 1 mmole per kg, 6 hr before the measurement, increased hepatic triglycerides by 100, 170 and 250%, respectively. After 1 mmole per kg, accumulation of hepatic triglycerides was maximum at 24 hr, reaching 9-fold the control value; liver histology showed microvesicular steatosis at 6 and 24 hr.
We conclude that tetracycline inhibits the mitochondrial oxidation of fatty acids in mice and in man. This effect may contribute to the development and severity of microvesicular steatosis observed after high doses of this antibiotic in man.