bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparison of Liver Ultrastructure in Salicylate Intoxication and Reye’s Syndrome
Authors: Partin Jacqueline S. , Daugherty Cynthia C. , Mcadams James A. , Partin John C. , Schubert William K. 
Published: August 2008

All childhood liver biopsy specimens from The Cincinnati Children’s Hospital Research Foundation which had been prepared for light and electron microscopy were reviewed to identify biopsies from children with salicylate intoxication. Only two cases of primary salicylate intoxication were identified. The histopathology and ultrastructural pathology were compared to that in two cases of Reye’s syndrome which were selected because they had been treated with salicylates and had comparable serum salicylate concentrations at the time of liver biopsy.
Liver biopsy specimens from the cases of salicylate intoxication were nearly normal by light microscopy. Lipid accumulation was minimal, and the content of glycogen and succinic acid dehydrogenase activity was normal. Mitochondria and peroxisomes appeared normal. Light and electron microscopy of liver specimens from the two cases of Reye’s syndrome revealed swollen hepatocytes with microvesicular fat and central nuclei. Glycogen content and succinic acid dehydrogenase activity were diminished. All hepatocyte mitochondria were enlarged, pleomorphic, and had an expanded matrix and no mitochondrial dense bodies. The histopathology and ultrastructural pathology of liver biopsy specimens in salicylate intoxication were different from those in Reye’s syndrome. In children in whom the diagnosis of Reye’s syndrome is obscure, liver biopsy with electron microscopic examination is necessary for definitive diagnosis.
Disposition and Metabolism of Metronidazole in Patients with Liver Failure
Authors: Farrell Geoffrey , Baird-Lambert Judith , Cvejic Mara , Buchanan Neil 
Published: August 2008

A pharmacokinetic study of metronidazole disposition was performed in 10 patients with severe liver disease, the majority of whom also had impaired renal function. Following a single intravenous dose, systemic clearance of metronidazole was decreased by 66% in patients compared with healthy controls (p < 0.001). The apparent volume of distribution for metronidazole was also decreased in patients (by 21%), but the greater effect on clearance resulted in the elimination half-life being prolonged 152%. Total urinary excretion of unaltered metronidazole was not reduced in patients compared with controls, and systemic clearance of metronidazole did not correlate with creatinine clearance.Hepatic production of hydroxymetronidazole [l-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroim-idazole], the major oxidative metabolite of metronidazole, was significantly lowered in patients with liver failure. Peak plasma levels of this metabolite were lower, the time taken to achieve peak levels was longer and the area under the plasma concentration ± time curve (AUC0-25h) was reduced in patients compared to controls (p < 0.05). Similarly, urinary recovery of hydroxymetronidazole was lower in patients with liver disease while excretion of the other major oxy-metabolite, 1-acetic acid-2-methyl-5-nitroimidazole, appeared reduced to an even greater extent. Thus, while the presence of renal function impairment in a patient with cirrhosis indicates that metronidazole elimination is likely to be abnormal, the principal mechanism for delayed elimination is impaired hepatic drug metabolism rather than reduced renal clearance of metronidazole and its major metabolites.
Serum α-L-Fucosidase: A New Marker for the Diagnosis of Primary Hepatic Carcinoma?
Authors: Deugnier Yves , David Véronique , Brissot Pierre , Mabo Philippe , Delamaire Damien , Messner Michel , Bourel Michel , Legall Jean-Yves 
Published: August 2008

α-L-fucosidase, a lysosomal enzyme which catabolizes fucoproteins, was studied in sera from 30 controls, 32 patients with primary hepatic carcinomas, 24 patients with secondary metastatic liver carcinomas and 36 patients with cirrhosis.
Serum α-L-fucosidase was increased in primary hepatic carcinomas (145.5 ± 12 nkat per liter) with a high statistical significance versus controls (51.4 ± 4.5 - p & 10−7), secondary metastatic liver carcinomas (58.9 ± 6.4 - p < 10−5) and cirrhotics (71.3 ± 6 - p < 10−5). A level exceeding 110 was a useful marker for the diagnosis of primary hepatic carcinoma with 75% sensitivity and 90% specificity.
Urea Synthesis After Protein Feeding Reflects Hepatic Mass in Rats† ‡
Authors: Brewer Thomas G. , Berry William R. , Harmon John W. , Walker Strothers H. , Dunn Michael A. 
Published: August 2008

Urea synthesis is an exclusive biosynthetic function of the liver. Since the exact relationship between urea synthesis in vivo and functional liver mass remains unclear, we established an animal model using oral protein loading and measurement of resultant urea synthesis in rats. We studied rats subjected to sham operation, 40% hepatectomy, 66% hepatectomy, portacaval shunt and CC14-induced cirrhosis. Urea synthesis was calculated as the sum of urinary urea excretion and accumulation of urea in body water during the 6-hr period after oral administration of a casein protein load equivalent to 20 gm per kg body weight.
Peak urea synthesis rate in the sham-operated group of rats was 142 ± 11 μmoles per hr per gm wet liver weight (mean ± 1 S.D.), 473 ± 34 μmoles per hr per gm liver protein and 80 ± 5 μmoles per hr per mg liver DNA. This rate closely matched those of the other groups for each type of liver mass measurement. Marked reduction (p < 0.01) of urea synthesis on a DNA basis was noted only in the CCl4-cirrhotic livers, related to the significantly higher (p < 0.01) DNA content of the cirrhotic livers. Similarly, increased (p < 0.05) liver protein content of the sham-operated rats when compared with the other groups was reflected in slightly lower urea synthesis rates expressed on the basis of liver protein (p < 0.05) when compared to that of all other groups. The slopes of the trend lines which define the relationship of urea synthesis rates in each group to total liver mass (liver weight, protein content and DNA content) were not significantly different.
We conclude that urea synthesis rates after oral administration of a protein load reflect liver mass in terms of wet weight, liver protein content and liver DNA content. This relationship remains valid in the presence of changes in liver parenchymal mass, portacaval shunting and CC14-cirrhosis.
UDP-Glucuronyltransferase-Catalyzed Deconjugation of Bilirubin Monoglucuronide
Authors: Cuypers Theo H.M. , Haar El Terlen M. , Jansen Peter L. M. 
Published: August 2008

Bilirubin monoglucuronide is rapidly deconjugated when incubated with UDP and rat liver microsomal preparations at pH 5.1. The following evidence was found that this reaction is catalyzed by UDP-glucuronyltransferase: (i) unconjugated bilirubin and UDP-glucuronic acid were identified as the reaction products; (ii) Gunn rat microsomal preparations lack bilirubin UDP-glucuronyltransferase deficiency and do not catalyze the deconjugation reaction, and (iii) neither saccharo-1,4-lactone, a β-glucuronidase inhibitor, nor butylated hydroxy toluene, an inhibitor of spontaneous isomerisation, affect the rate of the deconjugation reaction. Deconjugation appears to be the reverse of UDP-glucuronyltransferase-catalyzed glucuronidation.
The conditions for the reverse reaction differ in the following aspects from those of the forward reaction: (i) nucleotide triphosphates stimulate the reverse reaction probably allosterically; (ii) UDP-N-acetylglucosamine stimulates the forward reaction but has no effect on the reverse reaction; (iii) the optimal pH for the reverse reaction is pH 5.1 and for the forward reaction is pH 7.8, and (iv) Mg++ ion is not required for the reverse reaction but stimulates the forward reaction. Detergents stimulate both reactions. Stimulation of the reverse reaction by nucleotide triphosphates and detergents is mutually independent and additive which suggests different mechanisms of action.
Deconjugation reactions may become important during parenchymatous liver disease when, as a result of anaerobic glycolysis, intracellular pH decreases. Elevated levels of unconjugated bilirubin in the serum of patients with parenchymatous liver disease may be a sign of sick liver cells rather than decreased UDP-glucuronyltransferase activity.
The Comparative Effect of Administration of Substances Via the Hepatic Artery or Portal Vein on Hepatic Arterial Resistance, Liver Blood Volume and Hepatic Extraction in Cats
Authors: Lautt Wayne W. , Legare Dallas J. , Daniels Timothy R. 
Published: August 2008

Compounds reaching the liver do so via either the hepatic artery or the portal vein. This paper reports on the effectiveness of administration of compounds into these alternate routes for their effects on the hepatic parenchymal cells, the hepatic arterial resistance vessels (blood flow) and hepatic capacitance (blood volume responses). All tests were done on cats under pentobarbital anesthesia. Perfusion of the parenchymal cell mass was assessed by comparing the hepatic elimination of indocyanine green (ICG) administered via the two vascular routes. The ICG uptake was assessed by measuring relative areas under the hepatic venous outflow curve obtained following bolus injections of ICG into the artery and portal vein. In a separate series, using different methods, the hepatic venous levels reached early (2 min) and later (5 min) during a constant infusion were compared during administration via the two routes and found to be equal. Parenchymal cell functions (ICG extraction, bile salt stimulation of bile flow) indicate that blood from the artery and portal vein supplies the hepatic parenchymal cells equally well. This suggests a well-mixed blood supply prior to exposure of either blood stream to parenchymal cells. Substances being processed by the liver are thus equally well handled if reaching the liver via either the arterial or portal blood stream. This has significance in validating the use of some isolated liver perfusion methods that perfuse only via the portal vein.
Access of vasoactive compounds in the two blood streams to hepatic arterial resistance vessels was assessed using electromagnetic flow probes. The infusion of adenosine and angiotensin produced dilation and constriction respectively of the hepatic artery with the effect being about 3 times as large at a given dose when infused via the artery. The data show that vasoactive substances in the portal blood can affect the hepatic arterial blood flow by “transvascular” route and that portal blood has quite a high access to hepatic arterial resistance vessels. It does indicate, however, that the arterial resistance sites are not being perfused with mixed portal and arterial blood.
The hepatic blood volume changes in responses to intraportal and intraarterial infusions of angiotensin and noradrenaline were measured using an in vivo plethysmograph assembled around the intact liver. Constriction of hepatic blood volume was equal with administration via the two routes indicating that the capacitance vessels are perfused by well-mixed blood and are, therefore, likely to consist mostly of sinusoidal and postsinusoidal vessels with presinusoidal roles being minor or absent.
Hepatitis B Markers in United States Drug Addicts with Special Emphasis on the Delta Hepatitis Virus
Authors: Ponzetto Antonio , Seeff Leonard B. , Buskell-Bales Zelma , Ishak Kamal G. , Hoofnagle Jay H. , Zimmerman Hyman J. , Purcell Robert H. , Gerin John L. 
Published: August 2008

Hepatitis B virus and hepatitis delta virus co-infection in drug addicts has been well described in Europe, the latter agent appearing to have been introduced there in the mid-1970’s. Currently, similar data are scanty among United States addicts. We therefore reevaluated 99 drug addicts from three different geographic locations in the United States who had participated in a Veterans Administration Cooperative Study between 1972 and 1975. Almost all were asymptomatic, and all had been subjected to liver biopsy because of prolonged aminotransferase abnormalities. Stored sera were tested for antibody to hepatitis delta antigen (anti-HD) by radioimmunoassay and available liver biopsies examined for hepatitis delta antigen (HDAg) by immunofluorescence.
Overall, 19.2% were HBsAg positive, 9.1% HBeAg positive, 90% anti-HBc positive and 10.1%, positive for anti-HD. Anti-HD was identified in 42.1% of addicts who were HBsAg positive and in 3.3% who were anti-HBs positive. No correlation was found between HBeAg and anti-HD, but anti-HD was present significantly more frequently in those with chronic active hepatitis than in those with chronic persistent hepatitis. We conclude that hepatitis delta virus infection is common in HBsAg-positive drug addicts in the United States dating back to at least 1972 and probably earlier.
Liver Orcein Stain and Viral DNA in Duck Hepatitis B Virus Infection in Chinese Ducks and Experimentally Infected Japanese Ducklings
Authors: Mori Junko , Omata Masao , Yokosuka Osamu , Imazeki Fumio , Ito Yoshimi , Uchiumi Katsuo , Matsuyama Yasuhisa , Weifa Ye , Okuda Kunio 
Published: August 2008

Liver sections were stained with orcein, and duck hepatitis B virus was identified in sera and livers by the hybridization technique in 106 ducks (44 Chinese ducks, 15 Japanese ducks and 47 Japanese ducklings). Orcein-positive hepatocytes were found in 18 of 38 (47%) duck hepatitis B virus DNA seropositive ducks, and only in 3 of 68 (4%) seronegative ducks. The three ducks were all from a heavily infected flock in southern China.
Serial analyses of viral DNA by Southern blot and spot hybridizations in experimentally infected Japanese ducklings revealed a dissociation or a time gap between the amount of viral DNA in serum and the emergence of orcein positive hepatocytes. Orcein-positive hepatocytes were generally associated with prolonged presence of viral infection for at least 4 to 6 months. These findings support the clinical hypothesis that the presence of orcein-positive hepatocytes indicates persistent rather than acute infection.
Since orcein-positive hepatocytes have been seen in infection with hepatitis B, woodchuck hepatitis, ground squirrel and duck hepatitis B viruses, accumulation of orcein-positive material in liver cells may be one of the common properties these viruses share. This stain may be utilized for screening new hepatitis B virus-like viruses.
Effects of Propranolol on Azygos Venous Blood Flow and Hepatic and Systemic Hemodynamics in Cirrhosis
Authors: Bosch Jaime , Masti Ricardo , Kravetz David , Bruix Jordi , Gaya Joan , Rigau Joaquin , Rodes Joan 
Published: August 2008

The effects of propranolol on blood flow through gastroesophageal collaterals and on systemic and hepatic hemodynamies were investigated in 23 cirrhotic patients with portal hypertension. Gastroesophageal collateral blood flow was evaluated by the measurement of azygos venous blood flow by continuous thermal dilution. Azygos venous blood flow was markedly increased in these patients (544 ± 48 ml per min, as compared with 132 ± 18 ml per min in subjects without portal hypertension (p < 0.001).
Propranolol at doses achieving effective β-blockage (83 ± 5 mg) (mean ± S.E.M.) markedly reduced azygos venous blood flow (to 354 ± 34 ml per min, p < 0.001). Reduction of azygos venous blood flow (-34.2 ± 3.6%) was significantly greater (p < 0.01) than reductions in cardiac output (-22.6 ± 1.9%), hepatic venous pressure gradient (-11.5 ± 2.4%) and hepatic blood flow (-13.4 ± 7.4%). The hemodynamic effects of propranolol were not related to plasma norepinephrine levels.
Reduction of gastroesophageal collateral blood flow may be the mechanism by which oral propranolol therapy reduces the risk of repeated episodes of variceal bleeding in cirrhotic patients with portal hypertension.
Ethanol and arachidonic acid synergize to activate Kupffer cells and modulate the fibrogenic response via tumor necrosis factor α, reduced glutathione, and transforming growth factor β–dependent mechanisms
Authors: Cubero Francisco Javier , Nieto Natalia 
Published: August 2008

Abstract

Because of the contribution of ethanol and polyunsaturated fatty acids (PUFAs) to alcoholic liver disease, we investigated whether chronic ethanol administration and arachidonic acid (AA) could synergistically mediate Kupffer cell (KC) activation and modulate the stellate cell (HSC) fibrogenic response. Results: (1) the effects of ethanol and AA on KC and HSC were as follows: Cell proliferation, lipid peroxidation, H2O2, O2·−, nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase activity, and tumor necrosis factor alpha (TNF-α) were higher in KCethanol than in KCcontrol, and were enhanced by AA; HSCethanol proliferated faster, increased collagen, and showed higher GSH than HSCcontrol, with modest effects by AA. (2) AA effects on the control co-culture: We previously reported the ability of KC to induce a pro-fibrogenic response in HSC via reactive oxygen species (ROS)-dependent mechanisms; we now show that AA further increases cell proliferation and collagen in the control co-culture. The latter was prevented by vitamin E (an antioxidant) and by diphenyleneiodonium (a NADPH oxidase inhibitor). (3) Ethanol effects on the co-cultures: Co-culture with KCcontrol or KCethanol induced HSCcontrol and HSCethanol proliferation; however, the pro-fibrogenic response in HSCethanol was suppressed because of up-regulation of TNF-α and GSH, which was prevented by a TNF-α neutralizing antibody (Ab) and by l-buthionine-sulfoximine, a GSH-depleting agent. (4) Ethanol plus AA effects on the co-cultures: AA lowered TNF-α in the HSCcontrol co-cultures, allowing for enhanced collagen deposition; furthermore, AA restored the pro-fibrogenic response in the HSCethanol co-cultures by counteracting the up-regulation of TNF-α and GSH with a significant increase in GSSG and in pro-fibrogenic transforming growth factor beta (TGF-β).

Conclusion:

These results unveil synergism between ethanol and AA to the mechanism whereby KC mediate ECM remodeling and suggest that even if chronic ethanol consumption sensitizes HSC to up-regulate anti-fibrogenic signals, their effects are blunted by a second “hit” such as AA. (Hepatology 2008;48:2027-2039.)
Narrative change in psychotherapy: differences between good and bad outcome cases in cognitive, narrative, and prescriptive therapies
Authors: Moreira Paulo , Beutler Larry E. , Gonçalves Óscar F. 
Published: August 2008

AbstractThis study aimed to clarify the relationship between changes in the patients' narratives and therapeutic outcomes. Two patients were selected from three psychotherapeutic models (cognitive, narrative, and prescriptive therapies), one with good therapeutic outcome and the other with bad therapeutic outcome. Sessions from the initial, middle, and final phases for each patient were evaluated in terms of narrative structural coherence, process complexity, and content diversity. Differences between patients' total narrative production were found at the end of the therapeutic process. Good outcome cases presented a higher statistically significant total narrative change than poor outcome cases. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64:1–14, 2008.
Prolonged exposure to palmitate impairs fatty acid oxidation despite activation of AMP‐activated protein kinase in skeletal muscle cells
Authors: Pimenta A.S. , Gaidhu M.P. , Habib S. , So M. , Fediuc S. , Mirpourian M. , Musheev M. , Curi R. , Ceddia R.B. 
Published: August 2008

AbstractThe aim of this study was to investigate the chronic effects of palmitate on fatty acid (FA) oxidation, AMPK/ACC phosphorylation/activation, intracellular lipid accumulation, and the molecular mechanisms involved in these processes in skeletal muscle cells. Exposure of L6 myotubes for 8 h to 200, 400, 600, and 800 µM of palmitate did not affect cell viability but significantly reduced FA oxidation by ∼26.5%, ∼43.5%, ∼50%, and ∼47%, respectively. Interestingly, this occurred despite significant increases in AMPK (∼2.5‐fold) and ACC (∼3‐fold) phosphorylation and in malonyl‐CoA decarboxylase activity (∼38–60%). Low concentrations of palmitate (50–100 µM) caused an increase (∼30%) in CPT‐1 activity. However, as the concentration of palmitate increased, CPT‐1 activity decreased by ∼32% after exposure for 8 h to 800 µM of palmitate. Although FA uptake was reduced (∼35%) in cells exposed to increasing palmitate concentrations, intracellular lipid accumulation increased in a dose‐dependent manner, reaching values ∼2.3‐, ∼3‐, and 4‐fold higher than control in muscle cells exposed to 400, 600, and 800 µM palmitate, respectively. Interestingly, myotubes exposed to 400 µM of palmitate for 1 h increased basal glucose uptake and glycogen synthesis by ∼40%. However, as time of incubation in the presence of palmitate progressed from 1 to 8 h, these increases were abolished and a time‐dependent inhibition of insulin‐stimulated glucose uptake (∼65%) and glycogen synthesis (∼30%) was observed in myotubes. These findings may help explain the dysfunctional adaptations that occur in glucose and FA metabolism in skeletal muscle under conditions of chronically elevated circulating levels of non‐esterified FAs, such as in obesity and Type 2 Diabetes. J. Cell. Physiol. 217: 478–485, 2008. © 2008 Wiley‐Liss, Inc.
AVPR2 variants and mutations in nephrogenic diabetes insipidus: Review and missense mutation significance
Authors: Spanakis Elias , Milord Edrice , Gragnoli Claudia 
Published: August 2008

AbstractAlmost 90% of nephrogenic diabetes insipidus (NDI) is due to mutations in the arginine‐vasopressin receptor 2 gene (AVPR2). We retrospectively examined all the published mutations/variants in AVPR2. We planned to perform a comprehensive review of all the AVPR2 mutations/variants and to test whether any amino acid change causing a missense mutation is significantly more or less common than others. We performed a Medline search and collected detailed information regarding all AVPR2 mutations and variants. We performed a frequency comparison between mutated and wild‐type amino acids and codons. We predicted the mutation effect or reported it based on published in vitro studies. We also reported the ethnicity of each mutation/variant carrier. In summary, we identified 211 AVPR2 mutations which cause NDI in 326 families and 21 variants which do not cause NDI in 71 NDI families. We described 15 different types of mutations including missense, frameshift, inframe deletion, deletion, insertion, nonsense, duplication, splicing and combined mutations. The missense mutations represent the 55.83% of all the NDI published families. Arginine and tyrosine are significantly (P = 4.07E−08 and P = 3.27E−04, respectively) the AVPR2 most commonly mutated amino acids. Alanine and glutamate are significantly (P = 0.009 and P = 0.019, respectively) the least mutated AVPR2 amino acids. The spectrum of mutations varies from rare gene variants or polymorphisms not causing NDI to rare mutations causing NDI, among which arginine and tyrosine are the most common missense. The AVPR2 mutations are spread world‐wide. Our study may serve as an updated review, comprehensive of all AVPR2 variants and specific gene locations. J. Cell. Physiol. 217: 605–617, 2008. © 2008 Wiley‐Liss, Inc.