bluuebunny/crossref_metadata_2025_split huggingface dataset:
23-Methyl-3α, 7β-dihydroxy-5β-cholan-24-oic acid: Dose-response study of biliary secretion in rat
Authors: Roda Aldo , Aldini Rita , Grigolo Brunella , Simoni Patrizia , Roda Enrico , Pellicciari Roberto , Lenzi Pier Luigi , Natalini Benedetto 
Published: March 2007

A side chain derivative of ursodeoxycholic acid, 23-methylursodeoxycholic acid, was synthesized and the effect of i.v. infusion of the acid at different doses (0.75, 1.5, 3.0 and 6.0 μmoles per min per kg body weight over 1 hr) on bile flow, on its hepatic biotransformations and on biliary lipid secretion has been studied in bile fistula rats. The results were compared with those of ursodeoxycholic and cholic acid administered under similar conditions. 23-Methylursodeoxycholic acid is poorly secreted into bile and poorly taurine and glycine conjugated, at all infusion doses.
Ursodeoxycholic acid is quantitatively recovered at low doses and recovered less at high infusion rates. Cholic acid is almost entirely recovered at all infusion doses. Ursodeoxycholic acid conjugation pattern is dependent on the dose, and glucuronidation and sulfation operate at high doses. Cholic acid is taurine conjugated at low doses; at high doses, large amounts of unconjugated bile acids are observed. Methylursodeoxycholic acid presents a delayed secretion and hypercholeresis. Ursodeoxycholic acid presents similar results at high infusion rates, possibly by reaching a high intrahepatic concentration of free form. The octanol/water partition coefficients of ursodeoxycholic acid and 23-methylur-sodeoxycholic acid are similar and higher than that of cholic acid. A chole-hepatic shunting of 23-methylursodeoxycholic acid may explain both the low recovery in bile and hypercholeresis and is consistent with its hydrophobicity. The high water solubility and hydrophilicity of cholic acid, on the contrary, makes possible its high recovery in bile. The effect on biliary lipid secretion is unpredictable and affected by the dose and, in consequence, by the conjugation pattern of the bile acid. The detergency of the intrahepatic pool of the secreted bile acid and the physicochemical state of the native bile may be the driving force determinant for cholesterol and phospholipid biliary secretion.
Evoked potential abnormalities in children with chronic cholestasis
Authors: Cynamon Harry A. , Norcross Karyl , Isenberg Nevin J. 
Published: March 2007

To assess the effect of chronic cholestasis and vitamin E deficiency on nervous system function, we did multimodality evoked potential testing of 17 children (mean age = 47 months) who had chronic liver disease. Evoked potential testing was repeated periodically in 11 patients 1 to 33 months after the initial study.
Eight children had abnormal delays of the P100 peak of the visual evoked potential, and these children each had significantly higher total serum bile acid levels than did children who had normal visual evoked potentials (p = 0.002). Bilateral brainstem auditory evoked potential abnormalities consistent with conductive hearing losses were initially present in six patients. However, persistent conductive losses were found in four patients, all of whom had arteriohepatic dysplasia. Four children had mildly abnormal somatosensory evoked potentials that were due solely to a mild peripheral neuropathy. Biochemical measures of vitamin E status were not consistently associated with either normal or abnormal visual, brainstem auditory or somatosensory evoked potentials or a combination of evoked potential abnormalities, and an abnormality of one evoked potential type was not associated with an abnormality of any other. A similar lack of relationship between evoked potential results and plasma vitamin A measurement was noted. Following marked improvement in or resolution of cholestasis in four patients, the visual evoked potential became normal, but other evoked potentials did not change. Visual evoked potential improvement was greatest in two patients who underwent orthotopic liver transplantation.
This is the first report that demonstrates frequent, potentially reversible visual system abnormalities that are associated with cholestasis and cannot be attributed solely to vitamin E and/or A deficiency. Bilateral brainstem auditory evoked potential abnormalities consistent with conductive hearing losses were repeatedly present only in patients with arteriohepatic dysplasia and may represent another extrahepatic feature of this syndrome; we are not aware of any previous report of this association. Evoked potential studies provide a sensitive means with which to monitor neurological function and give objective, quantitative assessments necessary for comparing patients, and they may prove useful in understanding the pathophysiology of nervous system disorders associated with chronic cholestasis.
Ethanol-induced increase in cytosolic estrogen receptors in human male liver: A possible explanation for biochemical feminization in chronic liver disease due to alcohol
Authors: Villa Erica , Baldini Grazia M. , Rossini Gian Paolo , Pasquinelli Claudio , Melegari Margherita , Cariani Elisabetta , Tata Cristina , Bellentani Stefano , Ferrari Alberto , Manenti Federico 
Published: March 2007

The hepatic cytosolic estrogen receptor content was measured in liver samples from patients with normal livers and from patients with nonalcoholic cirrhosis, alcoholic cirrhosis and alcoholic hepatitis. The estrogen receptor content of normal liver was 5.2 ± 3.5 fmoles per mg of cytosolic protein. Levels which were not significantly different from this were found in the samples from patients with nonalcoholic cirrhosis (2.1 ± 2.0 fmoles per mg of cytosolic protein).
The cytosolic estrogen receptor content in the livers of patients with alcoholic cirrhosis who were abstaining was 4.2 ± 3.6 fmoles per mg of cytosolic protein, but it increased to 10.4 ± 4.9 fmoles per mg of protein in the livers of patients with alcoholic cirrhosis who were drinking, to 17.3 ± 8.7 fmoles per mg of protein in the livers of patients with alcoholic hepatitis with cirrhosis and to 22.7 ± 15.7 fmoles per mg of protein in the livers of patients with alcoholic hepatitis without cirrhosis.
Alcohol abuse appeared, therefore, to induce an increase in the estrogen receptor content of human liver, especially in patients who were drinking and had histological evidence of acute liver damage (alcoholic hepatitis).
The increase in hepatic estrogen receptor which we have observed may be involved in the molecular mechanisms underlying the feminization of the liver in alcoholic males.
Acyclovir in chronic hepatitis B virus infection
Authors: Dusheiko Geoffrey M. 
Published: March 2007

In a previous study a partial inhibition of viral replication was observed in HBeAg-positive patients after acyclovir (ACV) treatment.
To assess those results and to evaluate different treatment regimens, a randomized controlled trial with ACV given at 45 mg/kg/day by continuous infusion (in 5 patients) or by intermittent 8-hourly infusion (in 6 patients) for 28 days versus placebo has been performed in 20 patients affected by chronic hepatitis positive for both HBsAg and HBeAg for at least 6 months.
Patients were stratified for sex, presence of cirrhosis and homosexual activity.
Modest inhibition of serum DNA polymerase activity was observed after intermittent ACV treatment but not with the continuous infusion. After a 8-12 months follow-up, 2 of 10 of the ACV-treated patients and 3 of the controls had become HBe-Ag-negative, with 1 and 2 seroconversions to anti-HBe in the treated and placebo group respectively. No adverse effects were observed in ACV-treated patients after continuous infusion, but 2 of 6 patients who received intermittent therapy had to stop treatment, because of abdominal colics and elevation of the serum creatinine.
Our data confirm that ACV partially inhibits viral replication in HBeAg-positive patients but without significantly affecting the rate of seroconversion to anti-HBe.
Histological remission is recognized to follow loss of viral replication in chronic hepatitis B virus infection. The aim of antiviral therapies has been to accelerate seroconversion from HBeAg to anti-HBe, but so far none has been shown to be of significant advantage in adequate, controlled trials and toxicity has been common.
A randomized controlled trial of acyclovir, 45 mg/kg/day by continuous intravenous infusion for 28 days versus no therapy has been completed in 30 patients positive for HBsAg and HBeAg for a minimum of 6 months. Patients were stratified for sex, histology and homosexual activity.
Twenty-eight days therapy was associated with only a modest reduction in serum markers of viral replication. At 12-months DNAp was lost in 5/15 treated and 2/11 of the untreated group, while of the latter, 2 patients initially negative became positive. Seroconversion from HBeAg to anti-HBe had occurred in 4 of 15 treated and 1 of 15 untreated patients (95% confidence limits 12% and 51%) and was associated with histological improvement.
Acyclovir had only a weak effect on viral replication and did not significantly accelerate the rate of seroconversion to anti-HBe.
Hepatic innervation in hepatic regeneration
Authors: Cruise Jennifer L. 
Published: March 2007

The autonomic nervous system in rats has been assessed by means of indirect immunofluorescence using monospecific antibodies to neuron-specific enolase, neurofilaments, glial fibrillary acidic protein and S-100 protein [10 days after partial (70%) hepatectomy]. Different groups of rats were studied:
All rats of groups A and D showed normal liver/body weight ratios after 10 days in contrast to groups B and C where liver weights were 50-60% of the preresection weight. In group A the regeneration process was histologically normal and associated with a remarkable increase of autonomic innervation patterns in the portal triad. In contrast, livers of animals in groups B and C showed under the light microscope features of hepatocyte degeneration associated with a decreased autonomic innervation compared to the controls. The changes are identical in groups B and C, and are therefore irrespective of the type of blood deprivation (arterial or portal).
These results support the importance of dual blood supply for an optimal regenerative response in liver remnants after liver resection. We suggest that the autonomic nerve supply of the portal triad plays at least an important permissive role in liver regeneration.
Dynamics of hepatic connective tissue matrix constituents during murine schistosoma mansoni infection
Authors: Meneza Safaa El , Olds Richard G. , Kresina Thomas F. , Mahmoud Adel A. F. 
Published: March 2007

Hepatic fibrosis is the major clinical sequela of infection with the helminth Schistosoma mansoni. However, little is known regarding its dynamics and regulation in schistosomiasis. The present study presents the dynamics of deposition and resorption of two major extracellular matrix components of fibrosis, glycosaminoglycans and collagens, during the course of experimental S. mansoni infection. Early in infection (6 weeks), glycosaminoglycan biosynthesis was markedly elevated, as was collagen biosynthesis. This led to significant accumulations of these two molecules at a glycosaminoglycan/collagen ratio similar to that observed in livers of un-infected mice (uronic acid/hydroxyproline ratio of 1.10 at 6 weeks compared to normal value of 1.25). During maximal hepatic fibrosis (12 to 18 weeks), both collagen and glycosaminoglycan biosynthesis continued to increase but the extracellular matrix shifted to a lower glycosaminoglycan/collagen ratio of 0.42, suggesting enhanced glycosaminoglycan breakdown. In addition, during this acute stage of infection, Type I collagen was the predominant isotype synthesized, whereas total collagenolytic activity degrading Type I collagen was maximal.
During chronic infection, a decrease in the content of both hepatic glycosaminoglycans and collagens were noted, with a glycosaminoglycan/collagen ratio of 0.63. Decreased glycosaminoglycan content paralleled diminished biosynthetic rates. On the other hand, an over 50% reduction in collagen content (from 18 to 24 weeks) appeared not to result from diminished biosynthesis but from a switch in the predominant collagen isotype synthesized (from Type I to Type III), matched by an enhanced constitutive collagenolytic activity directed toward this type of collagen. These differences in the extracellular matrix separate schistosomal-induced hepatic fibrosis from most other types of fibrotic liver disease and may explain differences in the clinical manifestations observed during different stages of infection.
Long-term hemodynamic effects of ketanserin, a 5-hydroxytryptamine blocker, in portal hypertensive patients
Authors: Vorobioff Julio , Garcia-Tsao Guadalupe , Groszmann Roberto , Aceves Guillermo , Picabea Eduardo , Villavicencio Roberto , Hernandez-Ortiz Jorge 
Published: March 2007

Ketanserin, a 5-hydroxytryptamine-2 receptor blocker, has been shown to decrease portal pressure in recent acute hemodynamic studies that have been performed both in experimental animals and portal hypertensive patients. The present study was designed to investigate the effects of chronic oral administration of ketanserin in portal hypertensive patients with cirrhosis. The mean baseline hepatic venous pressure gradient in the 13 patients with alcoholic cirrhosis who completed the study was 15.7 ± 2.7 mmHg. It decreased significantly to 13.3 ± 2.0 mmHg (p < 0.001) after ketanserin was administered at a mean dose of 51 mg per day for a mean period of 32 days. This 14.6% reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure (from 22.2 ± 4.0 to 20.1 ± 3.6 mmHg) and was accompanied by significant decreases in cardiac index (18.8%) and in mean arterial pressure (8.1%). However, changes in cardiac index or in mean arterial pressure were not predictive of modifications in the hepatic venous pressure gradient. Eight of 16 patients entered in the study developed side effects, the most significant being a reversible portosystemic encephalopathy, which occurred in three patients who had poor liver function.
This study confirms evidence in favor of a role for 5-hydroxytryptamine in portal hypertension and adds a new group of agents for the chronic treatment of portal hypertensive patients.
Although the long-term oral administration of ketanserin reduces the mean portal pressure in patients with alcoholic cirrhosis and portal hypertension, the high incidence of side effects may limit its value, especially in patients who have a poor liver function.
Morphological and histological features of resected hepatocellular carcinoma in cirrhotic patients in the west
Authors: Kemeny François , Vadrot Jacqueline , Wu Andrew , Smadja Claude , Meakins Jonathan L. , Franco Dominique 
Published: March 2007

The pathological findings of 26 consecutive resections for hepatocellular carcinomas developing in cirrhotic patients were analyzed morphologically with a special interest in the presence of a capsule, vascular extension and satellite nodules. Tumor sizes varied from 2 to 11 cm. There were 20 expanding (76.9%) and six infiltrating tumors. Infiltrating tumors were significantly larger than expanding tumors (p<0.01). Histologically, the most common subgroups were the trabeculated pattern (65.4%) and the Edmonson-Steiner Type II (53.9%). Of the 20 expanding tumors, only six had direct spread in the liver parenchyma adjacent to the tumor (p<0.02). There was a significant relationship between the presence of a tumor extension in the distal portal branches and the presence of satellite nodules around the tumor (p<0.01). Survival at 6 months was significantly lower in patients with infiltrating (16.7%) than in those with expanding tumors (75%), (p<0.05).
The present results indicate that pathological features of hepatocellular carcinomas in cirrhotic patients in Western countries are similar to those encountered in the East: (a) tumors are frequently encapsulated; (b) the propensity for the tumor to spread is closely related to the presence of a tumor capsule. This study suggests that a thorough preoperative search for the capsule should be made whenever resection of a hepatocellular carcinoma in a cirrhotic patient is contemplated.
Controlled clinical trial of injection sclerotherapy for active variceal bleeding
Authors: Westaby David , Hayes Peter C. , Gimson Alexander E. S. , Polson Rex J. , Williams Roger 
Published: March 2007

In a prospective, randomized clinical trial, immediate injection sclerotherapy was compared with treatment by a combined infusion of vasopressin (0.4 unit per min) and nitroglycerin (40 to 400 μg per min) in 50 consecutive patients with 64 episodes of endoscopy-proven active variceal hemorrhage. Control of bleeding was assessed over a 12-hr period following entry into the trial. Patients in the vasopressin + nitroglycerin group were then treated by sclerotherapy, as were those in the sclerotherapy group who continued to bleed.
At 12 hr, bleeding was controlled in 29 (88%) of the 33 episodes treated by sclerotherapy compared with 20 (65%) of 3 episodes treated by vasopressin + nitroglycerin (p<0.05). Recurrence of variceal bleeding occurred at the same frequency (31%). Although admission mortality was less in those initially treated by sclerotherapy compared to those managed by vasopressin + nitroglycerin, this did not reach statistical significance (27 and 39%, respectively, p>0.20). Sclerotherapy carried out as the first treatment of the active variceal hemorrhage proved both safe and effective, even in the presence of major hemorrhage, and as compared to combined vasopressin and nitroglycerin it proved superior.
Nodular regenerative hyperplasia of the liver following bone marrow transplantation†
Authors: Snover Dale C. , Weisdorf Sally , Bloomer Joseph , McGlave Philip , Weisdorf Daniel 
Published: March 2007

Liver disease in the early period following bone marrow transplantation may be due to a number of causes, including pretransplant cytoreduction with chemotherapy and irradiation. Although the relationship of veno-occlusive disease to these agents has been well established, another process, nodular regenerative hyperplasia, may also occur.
In this retrospective study, we evaluated the incidence and clinical signs of these two processes as defined by histological criteria. In 103 patients studied, nine (8.8%) had venoocclusive disease and 23 (22.5%) had nodular regenerative hyperplasia. Venoocclusive disease was significantly associated with transplantation for malignancy other than acute or chronic leukemia and use of busulfan as a cytoreductive agent and occurred in younger patients. Nodular regenerative hyperplasia did not differ from the general transplant population in terms of underlying disease, cytoreductive regimen, graft vs. host disease prophylaxis or age. Both venoocclusive disease and nodular regenerative hyperplasia were associated with ascites. Venoocclusive disease had a poor prognosis, with eight of nine cases dying of or with venoocclusive disease, whereas no case of nodular regenerative hyperplasia died of liver disease and only 5 of 23 died with nodular regenerative hyperplasia. Using retrospective data, five of 11 patients fulfilling clinical criteria for the diagnosis of venoocclusive disease actually had nodular regenerative hyperplasia, as did all of nine patients fulfilling the criteria for “possible” venoocclusive disease.
These results indicate that nodular regenerative hyperplasia is a process which occurs commonly following bone marrow transplantation and which may be clinically misdiagnosed as venoocclusive disease.
Does hypophosphatemia play a role in acute liver failure?
Authors: Knochel James P. 
Published: March 2007

This is the first record of hypophosphataemia in acute liver failure induced by paracetamol; it occurred in most of the patients and was severe (<0.3 mmol/l) in more than one third. At this level hypophosphataemia produces impaired oxygen transport and tissue hypoxia, abnormal leucocyte function, depressed platelet numbers and function, generalised muscle weakness, and disorder of the central nervous system; these are frequent complications of acute liver failure. The similarity of the effects of liver failure and hypophosphataemia on the central nervous system (irritability, muscle weakness, dysarthria, confusion, and coma) suggests that phosphate depletion may be important in hepatic encephalopathy, and a progressive defect of phosphate metabolism in brain tissue of patients with chronic liver disease was shown recently by nuclear magnetic resonance spectroscopy.
The cause of hypophosphataemia in acute liver failure remains unclear. None of the recognised causes of moderate (0.3-0.7 mmol/l) hypophosphataemia correlated with the phosphate concentrations in our patients. The reduced maximum tubular reabsorption of phosphate in two patients suggests an increased loss of renal phosphate, perhaps due to a direct effect of paracetamol, although the correlation between plasma phosphate and creatinine concentrations suggests that renal failure may protect against hypophosphataemia. Because of the serious clinical implications of phosphate imbalance in acute liver failure the homoeostatic mechanisms of bone and renal phosphate reabsorption in this condition need to be studied urgently. Plasma phosphate concentrations should be monitored carefully during infusion of glucose in patients with liver failure.
Modulation of hepatic ferrochelatase activity by dietary manipulation of mitochondrial phospholipid fatty acyl groups†
Authors: Kools Ann M. , Straka James G. , Hill Hazel D. , Whitmer Dorothy I. , Holman Ralph T. , Bloomer Joseph R. 
Published: March 2007

Ferrochelatase is an enzyme bound to the inner mitochondrial membrane, which is important in heme biosynthesis. Activity of purified ferrochelatase is affected by the presence of certain fatty acids. In the present study, we examined whether the activity of ferrochelatase is altered by dietary manipulation of the composition of mitochondrial membrane phospholipid fatty acylgroups.
Rats were fed diets containing triolein, safflower or menhaden oil as 5% (w/w) of the diet. After 3 weeks, the animals were killed and liver mitochondria were isolated. Phospholipid fatty acid composition and ferrochelatase activity were assayed in the isolated mitochondria. Marked differences were seen. The proportion of oleic acid was highest in the triolein oil-fed group, that of linoleic and arachidonic acid was highest in the safflower oil-fed group and the proportion of eicosapentaenoic acid was highest in the menhaden oil-fed group. Ferrochelatase activity was greatest in the triolein oilfed group and lowest in the menhaden oil-fed group regardless of whether the mitochondria were intact, sonicated or sonicated and treated with Tween 20. Mixing of mitochondria from menhaden oil-fed rats with triolein oil resulted in a significant increase in ferrochelatase activity. Membrane fluidity and activities of the mitochondrial membrane enzymes succinic dehydrogenase and cytochrome oxidase did not differ among the groups.
We conclude that dietary manipulation of mitochondrial membrane phospholipid fatty acyl group composition can directly modulate hepatic ferrochelatase activity. This has potential application in the treatment of protoporphyria, the genetic disorder in which ferrochelatase activity is deficient.