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Liver
Kinds of Liver Terms modified by Liver Selected AbstractsMIXTURES OF BEEF TRIPE, BEEF LIVER AND SOYBEANS APPLIED TO FOOD DEVELOPMENTJOURNAL OF FOOD PROCESSING AND PRESERVATION, Issue 3 2007L. MALVESTITI ABSTRACT A nutritive sausage-type product was developed with beef tripe, beef liver and soybeans as ingredients. A three-component mixture design was used to obtain seven different formulations (minimum of each main ingredient: 16.5%, maximum: 67.0%). Ingredients were ground, mixed and packed tightly with a polypropylene film to obtain a roll. Pieces were cooked in boiling water for 90 min. The composition of the obtained products varied within the following ranges: proteins 17.32,25.56 g/100 g, lipids 3.22,3.87 g/100 g, crude fiber 1.50,4.50 g/100 g, minerals 1.44,2.72 g/100 g. Total iron levels varied between 1.39 and 2.98 mg/100 g and calcium levels between 15.07 and 34.01 mg/100 g. Surface response analysis was applied to parameters obtained from texture profile analysis (hardness, adhesiveness, cohesiveness and elasticity). Products hardness increased when the soy content increased; on the contrary, formulations enriched in beef tripe were those of higher elasticity and cohesiveness. Color was mainly determined by the incorporation of liver. A nontrained panel was used to evaluate the acceptance of the different formulations. The most accepted one was that with equal proportions of the three main ingredients. Microbiological challenge testing showed that the thermal treatment was enough for assuring the product safeness even in samples with high initial microbial charge. [source] NG -NITRO- l -ARGININE METHYL ESTER POTENTIATES ANAPHYLACTIC VENOCONSTRICTION IN RAT PERFUSED LIVERSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2006Toshishige Shibamoto SUMMARY 1The effects of the nitric oxide (NO) synthase inhibitor NG -nitro- l -arginine methyl ester (l -NAME) on anaphylaxis-induced venoconstriction were examined in rat isolated livers perfused with blood-free solutions in order to clarify the role of NO in anaphylactic venoconstriction. 2Rats were sensitized with ovalbumin (1 mg) and, 2 weeks later, livers were excised and perfused portally in a recirculating manner at a constant flow with Krebs',Henseleit solution. The antigen (ovalbumin; 0.1 mg) was injected into the reservoir 10 min after pretreatment with l-NAME (100 mmol/L) or d -NAME (100 mmol/L) and changes in portal vein pressure (Ppv), hepatic vein pressure (Phv) and perfusate flow were monitored. In addition, concentrations of the stable metabolites of NO ( and ) were determined in the perfusate using an HPLC,Griess system. 3The antigen caused hepatic venoconstriction, as evidenced by an increase in Ppv from a mean (SEM) baseline value of 7.7 ± 0.1 cmH2O to a peak of 21.4 ± 1.1 cmH2O at 3 min in d -NAME-pretreated livers. Pretreatment with l-NAME augmented anaphylactic venoconstriction, as reflected by a higher Ppv (27.4 ± 0.8 cmH2O) after antigen than observed following d -NAME pretreatment. The addition of l -arginine, a precursor for the synthesis of NO, reversed the augmentation of anaphylactic venoconstricion by l -NAME. This suggests that hepatic anaphylaxis increased the production of NO, which consequently attenuated anaphylactic venoconstriction. However, perfusate NOx levels did not increase significantly after antigen in livers pretreated with either l -NAME or d -NAME. 4In conclusion, l -NAME potentiates rat anaphylactic hepatic venoconstriction, suggesting that NO contributes to the attenuation of the venoconstriction. However, this functional evidence was not accompanied by corresponding changes in perfusate NOx concentrations. [source] Oral toxicity of the cyanobacterial toxin cylindrospermopsin in male Swiss albino mice: Determination of no observed adverse effect level for deriving a drinking water guideline valueENVIRONMENTAL TOXICOLOGY, Issue 2 2003A. R. Humpage Abstract The cyanobacterial toxin cylindrospermopsin (CYN) is a frequent contaminant of freshwaters throughout the world, including those that are sources of drinking water. The first cases of human poisoning attributed to this toxin occurred from a treated drinking water supply in Queensland, Australia, in 1979. The toxin causes extensive damage to the liver, kidneys, spleen, heart, and other organs. It is known to be a potent protein synthesis inhibitor, but there is mounting evidence for genotoxicity and that it metabolizes to even more toxic forms. As part of a risk assessment process leading to a guideline for a safe drinking water level for this toxin, we performed a series of experiments to determine a no-observed-adverse-effect level (NOAEL) for this toxin. In the first trial male mice were exposed to CYN-containing cyanobacterial extract in their drinking water (0,657 ,g CYN kg,1 day,1) for 10 weeks. In the second trial mice received purified CYN by daily gavage (0,240 ,g CYN kg,1 day,1) for 11 weeks. Body and organ weights were recorded; urine, serum, and hematology analyses were performed; and histopathological examination of tissues was carried out. Body weights were significantly increased at low doses (30 and 60 ,g kg,1 day,1) and decreased at high doses (432 and 657 ,g kg,1 day,1). Liver and kidney weights were significantly increased at doses of 240 ,g kg,1 day,1 and 60 ,g kg,1 day,1, respectively. Serum bilirubin levels were significantly increased and bile acids significantly decreased at doses of 216 ,g kg day,1 and greater. Urine total protein was significantly decreased at doses above 60 ,g kg,1 day,1. The kidney appeared to be the more sensitive organ to this toxin. If it is assumed that increased organ weights and changes in functional capacity are responses to an underlying toxic effect, then the NOAEL based on this data is 30 ,g kg,1 day,1, which, with standard calculations and uncertainty factors, provides a proposed guideline safety value of 1 ,g/L in drinking water. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 94,103, 2003. [source] Tumor prevalence and biomarkers of exposure and response in brown bullhead (Ameiurus nebulosus) from the Anacostia River, Washington, DC and Tuckahoe River, Maryland, USAENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2004Alfred E. Pinkney Abstract We valuated liver and skin tumor prevalence and biomarkers of exposure and response in brown bullhead (Ameiurus nebulosus) from three locations in the Anacostia River (Washington, DC, USA), a Chesapeake Bay region of concern. The Tuckahoe River (Maryland, USA) served as a reference. Each river was sampled in fall 2000 and spring 2001. In the Anacostia, prevalence of liver tumors was 50 to 68%, and prevalence of skin tumors was 13 to 23% in large (,260 mm, age ,3 years) bullheads. Liver and skin tumor prevalence was 10 to 17% and 0%, respectively, in small (150,225 mm, age 1,2 years) bullheads. Tuckahoe bullhead liver tumor prevalence was 0 to 3% (large) and 0% (small); none had skin tumors. Biliary polynuclear aromatic hydrocarbon (PAH)-like fluorescent metabolites and liver DNA adduct concentrations were elevated in large and small Anacostia bullheads. Mean adduct concentrations were 16 to 28 times higher than those in Tuckahoe fish. Chromatograms revealed a diagonal radioactive zone, indicating polycyclic aromatic compound (PAC)-DNA adducts. The biomarker data and the 10 to 17% liver tumor prevalence at ages 1 to 2 suggest that these year classes are likely to have a high prevalence as they reach age 3 and older. This study provides the strongest evidence to date of the role of PAHs in tumor development in Anacostia bullheads. [source] Oral bioavailability and toxicokinetics of 3,3,,4,4,,5-pentachlorobiphenyl in northern leopard frogs, Rana pipiensENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2000Yue-wern Huang Abstract This study is the first report on oral bioavailability, whole-body elimination, and distribution of a specific polychlorinated biphenyl (PCB) congener on an amphibian species, northern leopard frogs. Each frog was orally dosed once with either 0.35 or 5.0 mg/kg PCB 126 (based on frog wet wt), including tracer 14C-PCB 126 (3,,4,,5,-phenyl-ring- 14C) by force feeding it a cricket injected with the PCB. We found no statistical difference (t = 0.917, df = 5, p = 0.401) in the average 48-h oral bioavailabilities of 0.35- and 5.0-mg/kg dosage groups, which were 84.6 ± 5.8% (mean ± SE, n = 4) and 90.9 ± 1.5% (n = 3), respectively. Statistical analysis indicated that time was the only independent variable affecting the retention of whole-body 14C content. Kinetics were apparently first order because elimination rate was independent of dose. Assuming a single pool and one elimination rate, the t1/2 value for whole-body elimination of PCB-derived 14C was 763 d. Liver, fat bodies (corpora adiposa), carcass (head, bone, cartilage materials, and residues of other tissues), skin, and muscle were the major organs for PCB 126 retention in both dosage groups. The concentrations of 14C residue in fat bodies were relatively constant throughout the experiment. However, total residues in fat bodies declined throughout the experiment in both dosage groups in correlation with declining masses of fat bodies. Gonad, kidney, stomach, intestine, and a tissue pool including esophagus, lung, spleen, heart, and cloacal materials each accumulated <1% of the initial total 14C residue. The egg follicles in 19 females contained 1 to 23% of the initial total 14C residue, with an average of 10.0 ± 9.2% (mean ± SE, n = 19). [source] Using regional exposure criteria and upstream reference data to characterize spatial and temporal exposures to chemical contaminants,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2000Susan M. Cormier Abstract Analyses of biomarkers in fish were used to evaluate exposures among locations and across time. Two types of references were used for comparison, an upstream reference sample remote from known point sources and regional exposure criteria derived from a baseline of fish from reference sites throughout Ohio, USA. Liver, bile, and blood were sampled from white suckers (Catostomus commersoni) and common carp (Cyprinus carpio) collected during 1993 and 1996 in the Ottawa River near Lima, Ohio. Levels of exposure were measured for petroleum by naphthalene-type metabolites, combustion by-products by benzo[a]pyrene-type metabolites, coplanar organic compounds by ethoxyresorufin- O -deethylase (EROD) activity, and urea by blood urea nitrogen (BUN) levels. The four biomarkers analyzed proved effective in determining differences between reference and polluted sampling sites, between geographically close (<0.5 km) sites, and between sampling years at sites common in both years. Calculated exposure criteria levels of the polycyclic aromatic hydrocarbon bile metabolites were found to be a conservative approximation of levels from a designated reference site and could thereby permit comparison of biomarker levels of fish from the Ottawa River to a regional reference level. Polycyclic aromatic hydrocarbon bile metabolite and EROD activity levels were more reflective of spatial patterns of contamination than BUN, although all biomarkers indicated differences overtime. Biomarkers from white suckers seemed to be more responsive in detecting changes in contaminant levels than the same biomarkers from common carp. Lower levels in 1996 of all biomarkers at many sites suggested lower exposures than in 1993 and could be indicative of some improvement over the period. [source] Book and Media ReviewsADDICTION BIOLOGY, Issue 4 2002Article first published online: 9 JUN 200 Book Reviewed in this article Diseases of the Liver and Biliary System, 11th edition SHEILA SHERLOCK & JAMES DOOLEY Medicine and Literature JOHN SALINSKY Neuropsychiatry: An Introductory Approach DAVID ARCINIEGAS & THOMAS BERESFORD [source] Development of an Improved Technique for the Perfusion of the Isolated Caudal Lobe of Sheep LiverEXPERIMENTAL PHYSIOLOGY, Issue 5 2000A. M. Ali The study was designed to develop an improved technique for perfusing the isolated caudal lobe of sheep liver. Twenty caudal lobes were perfused for 3-4 h, in a non-recirculating mode, with Krebs-Henseleit bicarbonate buffer. The perfusion system was designed to give a constant flow. The hepatic viability and functional normality of the perfused lobe were assessed by measuring the perfusion flow rate, pH, K+ efflux, O2 uptake, substrate uptake, gluconeogenesis from propionate and amino acids, and ureagenesis from ammonia and amino acids. Liver tissue was sampled for histological examination, as well as for the determination of liver glycogen and wet: dry weight ratio. The perfusion flow rate and pH were both stable throughout the perfusion. The potassium concentration in the effluent perfusate did not increase during the perfusion, suggesting that there was no loss of viability or hypoxia. The perfused lobe extracted more than 50% of the O2 supply. The rate of oxygen consumption was comparable to the rate reported in vivo. The initial glycogen content was reduced by about 40% after 4 h perfusion. The wet: dry weight ratio was 3.6, consistent with the absence of tissue oedema. Urea production was stimulated when NH4Cl (0.3 mM) was added to the medium but there was no significant increase in urea release when alanine (0.15 mM), glutamine (0.2 mM) or lysine (0.2 mM) was added. Urea production, however, increased by about 171% when a physiological mixture of amino acids was added. Propionate (0.5 mM), alanine and glutamine stimulated glucose production but not lysine or the complete amino acid mixture. Glutamine release was lower than that reported in the rat liver. Changing the direction of flow also revealed an apparent difference between livers from sheep and rats in their metabolism of ammonia. The improved technique offers a simple practical and inexpensive approach to many problems in ruminant physiology and nutritional biochemistry. [source] Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 Revised Version)HEPATOLOGY RESEARCH, Issue 7 2010Masatoshi Kudo The World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST) are inappropriate to assess the direct effects of treatment on the hepatocellular carcinoma (HCC) by locoreginal therapies such as radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted for HCC is needed urgently in the clinical practice as well as in the clinical trials of HCC treatment, such as molecular targeted therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2009 by Liver Cancer Study Group of Japan based on the 2004 version of RECICL, which was commonly used in Japan. Major revised points of the RECICL 2009 is to provide TE4a (Complete response with enough ablative margin) and TE4b (complete response without enough ablative margin) for local ablation therapy. Second revised point is that setting the timing at which the overall treatment effects are assessed. Third point is that emergence of new lesion in the liver is regarded as progressive disease, different from 2004 version. Finally, 3 tumor markers including alpha-fetoprotein (AFP) and AFP-L3 and des-gamma-carboxy protein (DCP) were also added for the overall treatment response. We hope this new treatment response criteria, RECICL, proposed by Liver Cancer Study Group of Japan will benefit the HCC treatment response evaluation in the setting of the daily clinical practice and clinical trials as well not only in Japan, but also internationally. [source] Liver and immune disorderHEPATOLOGY RESEARCH, Issue 2007Hiromi Ishibashi No abstract is available for this article. [source] Drug-eluting bead therapy in primary and metastatic disease of the liverHPB, Issue 7 2009Stewart Carter Abstract Background:, Drug-eluting bead transarterial chemoembolization (DEB-TACE) is a novel therapy for the treatment of hypervascuarized tumours. Through the intra-arterial delivery of microspheres, DEB-TACE allows for embolization as well as local release of chemotherapy in the treatment of hepatic malignancy, providing an alternative therapeutic option in unresectable tumours. Its role as an adjunct to surgical resection or radiofrequency ablation (RFA) is less clear. The purpose of this review is to summarize recent studies investigating DEB-TACE in order to better define safety, efficacy and outcomes associated with its use. Methods:, A systematic review of all published articles and trials identified nine clinical trials and 23 abstracts. These were reviewed for tumour histology, stage of treatment, delivery technique, outcome at follow-up, complications and mortality rates. Results:, Publications involved treatment of hepatocellular carcinoma (HCC), metastatic colorectal carcinoma (MCRC), metastatic neuroendocrine (MNE) disease and cholangiocarcinoma (CCA). Using Response Evaluation Criteria in Solid Tumours (RECIST) or European Association for the Study of the Liver (EASL) criteria, studies treating HCC reported complete response (CR) rates of 5% (5/101) at 1 month, 9% (8/91) at 4 months, 14% (19/138) at 6 months and 25% (2/8) at 10 months. Partial response (PR) was reported as 58% (76/131) at 1 month, 50% (67/119) at 4 months, 57% (62/108) at 6,7 months and 63% (5/8) at 10 months. Studies involving MCRC, CCA and MNE disease were less valuable in terms of response rate because there is a lack of comparative data. The most common procedure-associated complications included fever (46,72%), nausea and vomiting (42,47%), abdominal pain (44,80%) and liver abscess (2,3%). Rather than reporting individual symptoms, two studies reported rates of post-embolic syndrome (PES), consisting of fever, abdominal pain, and nausea and vomiting, at 82% (75/91). Six of eight studies reported length of hospital stay, which averaged 2.3 days per procedure. Mortality was reported as occurring in 10 of 456 (2%) procedures, or 10 of 214 (5%) patients. Conclusions:, Drug-eluting bead TACE is becoming more widely utilized in primary and liver-dominant metastatic disease of the liver. Outcomes of success must be expanded beyond response rates because these are not a reliable surrogate for progression-free survival or overall survival. Ongoing clinical trials will further clarify the optimal timing and strategy of this technology. [source] Interpreting three-dimensional structures from two-dimensional images: a web-based interactive 3D teaching model of surgical liver anatomyHPB, Issue 6 2009Jodi L. Crossingham Abstract Background:, Given the increasing number of indications for liver surgery and the growing complexity of operations, many trainees in surgical, imaging and related subspecialties require a good working knowledge of the complex intrahepatic anatomy. Computed tomography (CT), the most commonly used liver imaging modality, enhances our understanding of liver anatomy, but comprises a two-dimensional (2D) representation of a complex 3D organ. It is challenging for trainees to acquire the necessary skills for converting these 2D images into 3D mental reconstructions because learning opportunities are limited and internal hepatic anatomy is complicated, asymmetrical and variable. We have created a website that uses interactive 3D models of the liver to assist trainees in understanding the complex spatial anatomy of the liver and to help them create a 3D mental interpretation of this anatomy when viewing CT scans. Methods:, Computed tomography scans were imported into DICOM imaging software (OsiriXÔ) to obtain 3D surface renderings of the liver and its internal structures. Using these 3D renderings as a reference, 3D models of the liver surface and the intrahepatic structures, portal veins, hepatic veins, hepatic arteries and the biliary system were created using 3D modelling software (Cinema 4DÔ). Results:, Using current best practices for creating multimedia tools, a unique, freely available, online learning resource has been developed, entitled Visual Interactive Resource for Teaching, Understanding And Learning Liver Anatomy (VIRTUAL Liver) (http://pie.med.utoronto.ca/VLiver). This website uses interactive 3D models to provide trainees with a constructive resource for learning common liver anatomy and liver segmentation, and facilitates the development of the skills required to mentally reconstruct a 3D version of this anatomy from 2D CT scans. Discussion:, Although the intended audience for VIRTUAL Liver consists of residents in various medical and surgical specialties, the website will also be useful for other health care professionals (i.e. radiologists, nurses, hepatologists, radiation oncologists, family doctors) and educators because it provides a comprehensive resource for teaching liver anatomy. [source] Effect of Cadmium and Aluminum Intake on the Antioxidant Status and Lipid Peroxidation in Rat TissuesJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2001Shohda A. El-Maraghy Abstract This work aimed to study the relationship between the accumulation of cadmium (Cd) or aluminum (Al) in certain tissues and the levels of lipid peroxides as well as tissue antioxidants. To carry out such investigations, CdCl2 was given to rats in two dose levels; 0.5 or 2.0 mg/kg i.p for 1 day or daily repeated doses for 2 weeks. Al was given as AlCl3 either in a single dose of 100 mg/kg or daily repeated doses of 20 mg/kg for 2 and 4 weeks. The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation) and reduced glutathione (GSH) levels as well as the activities of glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-R), and glucose-6-phosphate dehydrogenase (G-6-PDH) enzymes. Liver and kidney functions were assessed by measuring serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities as well as serum urea and creatinine concentrations. Cd and Al concentrations in the studied tissues were also measured. Results indicated that tissue Cd was significantly increased after administration of either Cd doses. After a single dose of 0.5 or 2.0 mg/kg CdCl2, the increase in tissue Cd levels were accompanied by an increase in MDA and a decrease in GSH levels. On the other hand, after repeated administration of Cd, tissue Cd accumulation was accompanied by increased hepatic and renal GSH levels with decrease in MDA content and a decrease in GSH-PX activity in liver. Liver function was affected at all dose regimens, whereas kidney function was affected only after 2 weeks administration of the higher dose. In Al treated rats, Al concentration was shown to be increased in liver much more than in brain. This was accompanied by a slight decrease in hepatic GSH level after 2 weeks and a decrease in GSH-PX activity after 4 weeks. Liver function was affected only after repeated injection of Al for 2 or 4 weeks. In general, Al administration exhibited safer pattern than Cd. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:207,214, 2001 [source] Cholesterol-Sensing Receptors, Liver × Receptor , and ,, Have Novel and Distinct Roles in Osteoclast Differentiation and ActivationJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2006Kirsten M Robertson Abstract The liver × receptor (,,,) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXR,,/,, LXR,,/,, and LXR,,/,,,/, mice show that both LXR, and , are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. Introduction: The liver × receptors (,,,) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. Materials and Methods: pQCT was performed on both male and female LXR,,/,, LXR,,/,, LXR,,/,,,/,, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. Results: At the mRNA level, LXR, was more highly expressed than LXR, in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXR,,/, mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXR,,/, mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. Conclusions: Our findings show that both LXRs influence cellular function within the bone, with LXR, having an impact on osteoclast activity, primarily in cortical bone, whereas LXR, modulates trabecular bone turnover. [source] Determination and Confirmation of Chloramphenicol Residues in Swine Muscle and LiverJOURNAL OF FOOD SCIENCE, Issue 1 2002T.L. Li ABSTRACT: Average high-performance liquid chromatography (HPLC) recoveries of chloramphenicol (CAP) in swine muscle and liver ranged from 91.3 to 94.2% and 93.1 to 103.7%, respectively, with coefficients of variation ranging from 1.4 to 4.3% and 1.1 to 11.2% for each tissue sample. The method described was repeatable and reproducible in swine muscle and liver, with a limit of quantification of 15 ng/mL and a limit of detection estimated at 5 ng/mL. The limit of identification of CAP was 25 ng/mL, 5ng/mL, and 20 ng/mL for HPLC/PDA, GC/MS selected ion monitoring (SIM), and LC/MS analysis, respectively. [source] Minimal hepatic encephalopathy: Consensus statement of a working party of the Indian National Association for Study of the LiverJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2010Radha K Dhiman Abstract Hepatic encephalopathy (HE) is a major complication that develops in some form and at some stage in a majority of patients with liver cirrhosis. Overt HE occurs in approximately 30,45% of cirrhotic patients. Minimal HE (MHE), the mildest form of HE, is characterized by subtle motor and cognitive deficits and impairs health-related quality of life. The Indian National Association for Study of the Liver (INASL) set up a Working Party on MHE in 2008 with a mandate to develop consensus guidelines on various aspects of MHE relevant to clinical practice. Questions related to the definition of MHE, its prevalence, diagnosis, clinical characteristics, pathogenesis, natural history and treatment were addressed by the members of the Working Party. [source] In vivo magnetic resonance imaging of iron oxide,labeled, arterially-injected mesenchymal stem cells in kidneys of rats with acute ischemic kidney injury: Detection and monitoring at 3TJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2007Harald Ittrich MD Abstract Purpose To evaluate MRI for a qualitative and quantitative in vivo tracking of intraaortal injected iron oxide,labeled mesenchymal stem cells (MSC) into rats with acute kidney injury (AKI). Materials and Methods In vitro MRI and R2* measurement of nonlabeled and superparamagnetic iron oxide (SPIO)-labeled MSC (MSCSPIO) was performed in correlation to cellular iron content and cytological examination (Prussian blue, electron microscopy). In vivo MRI and R2* evaluation were performed before and after ischemic/reperfusion AKI (N = 14) and intraaortal injection of 1.5 × 106 MSCSPIO (N = 7), fetal calf serum (FCS) (medium, N = 6), and SPIO alone (N = 1) up to 14 days using a clinical 3T scanner. Signal to noise ratios (SNR), R2* of kidneys, liver, spleen, and bone marrow, renal function (creatinine [CREA], blood urea nitrogen [BUN]), and kidney volume were measured and tested for statistical significance (Student's t -test, P < 0.05) in comparison histology (hematoxylin and eosin [H&E], Prussian blue, periodic acid-Schiff [PAS], CD68). Results In vitro, MSCSPIO showed a reduction of SNR and T2* with R2* , number of MSCSPIO (R2 = 0.98). In vivo MSCSPIO administration resulted in a SNR decrease (35 ± 15%) and R2* increase (101 ± 18.3%) in renal cortex caused by MSCSPIO accumulation in contrast to control animals (P < 0.01). Liver, spleen, and bone marrow (MSCSPIO) showed a delayed SNR decline/R2* increase (P < 0.05) resulting from MSCSPIO migration. The increase of kidney volume and the decrease in renal function (P < 0.05) was reduced in MSC-treated animals. Conclusion Qualitative and quantitative in vivo cell-tracking and monitoring of organ distribution of intraaortal injected MSCSPIO in AKI is feasible in MRI at 3T. J. Magn. Reson. Imaging 2007;25:1179,1191. © 2007 Wiley-Liss, Inc. [source] Difference in susceptibilities of different cell lines to bilirubin damageJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1 2000K-C Ngai Objective: To investigate if there are differences in susceptibilities to bilirubin toxicity of different cell lines. Methodology: A modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method was adopted to study the cytotoxic effect of bilirubin on several commercially available cell lines including human glioblastoma (ATCC CRL 1690, T98G), human neuroblastoma (ATCC HTB-10, SK-N-MC), human liver (ATCC CCL 13, Chang Liver, HeLa markers) and a mouse fibroblast (ATCC CCL-1, NCTC Colon 929). Results: Cytotoxicity was observed when certain bilirubin:albumin molar ratios were exceeded in the medium of a cell line in culture. Different cells exhibited different susceptibilities to the cytotoxic effects of bilirubin; neuroblastoma and glioblastoma were most susceptible, fibroblasts were the least vulnerable. Conclusions: Our findings have confirmed the clinical impression that different cells sustain different degrees of cytotoxicities caused by bilirubin. [source] Differential Changes in MAP Kinases, Histone Modifications, and Liver Injury in Rats Acutely Treated With EthanolALCOHOLISM, Issue 9 2010Annayya R. Aroor Background:, Acute ethanol is known to affect cells and organs but the underlying molecular mechanisms are poorly explored. Recent developments highlight the potential importance of mitogen-activated protein kinases, MAPKs (i.e., ERK1/2, p38, and JNK1/2) signaling, and histone modifications (i.e., acetylation, methylation, and phosphorylation) in the actions of ethanol in hepatocytes. We have therefore investigated significance of these molecular steps in vivo using a model in which rats were acutely administered ethanol intraperitoneally (IP). Methods:, Ethanol was administered IP (3.5 gm/kg body weight) to 12-week-old male Sprague,Dawley rats. Liver was subsequently removed at 1 and 4 hours. Serum was used for alcohol and ALT assays. At the time of the removal of liver, small portions of each liver were formalin-fixed and stained with hematoxylin and eosin (H&E) and used for light microscopy. Western blot analysis was carried out with specific primary antibodies for various parameters. Results:, There were clear differences at 1 and 4 hours in blood ethanol, ALT, steatosis, and cleaved caspase 3. Apoptosis at 1 hour was followed by necrosis at 4 hours. Acute alcohol elicited a marked increase in the phosphorylation of ERK1/2 and moderate increases in the phosphorylation of p38 MAPK and JNK. Temporally different phosphorylation of histone H3 at ser-10 and ser-28 occurred and acetylation of histone H3 at lys 9 increased progressively. Conclusions:, There were distinct differences in the behavior of the activation of the 3 MAP kinases and histone modifications after acute short exposure of liver to ethanol in vivo. Although all 3 MAPKs were rapidly activated at 1 hour, the necrosis, occurring at 4 hours, correlated to sustained activation of ERK1/2. Transient activation of p38 is associated with rapid phosphorylation of histone H3, whereas prolonged activation of ERK1/2 is correlated to persistent histone H3 acetylation. [source] Uptake and Dispersion of Metformin in the Isolated Perfused Rat LiverJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2000CHEN-HSI CHOU Although metformin is a widely used oral antihyperglycaemic, the exact mechanisms of its cellular uptake and action remain obscure. In this study the hepatic extraction and disposition kinetics of metformin were investigated by use of an isolated in-situ rat liver preparation. The liver was perfused in single-pass mode with protein-free Krebs bicarbonate medium at a flow rate of 20mLmin,1. During constant infusion with 1 mgL,1 metformin hydrochloride the hepatic uptake of metformin approached equilibrium within 10 min. The steady-state availability, F, determined from the ratio of outflow concentration to input concentration, was 0.99±0.02 (mean±s.d., n=4). The outflow profile of metformin resulting from a bolus injection of 25 ,g into the portal vein, had a sharp peak then a slower declining terminal phase. The mean transit time (MTT; 49.5±14.5, n = 6) and normalized variance (CV2; 4.13±0.05) of the hepatic transit times of metformin were estimated by numerical integration from the statistical moments of the outflow data. The volume of distribution of metformin in the liver (1.58±0.28 mL (g liver),1) was estimated from its MTT. The volume of distribution is greater than the water space of liver, indicating that metformin enters the hepatic aqueous space and becomes distributed among cellular components. The magnitude of CV2 for metformin is greater than for the vascular marker sucrose, suggesting that distribution of metformin into hepatic tissue is not instantaneous. In conclusion, hepatic uptake of metformin is rate-limited by a permeability barrier. Although metformin is accumulated in the liver, the organ does not extract it. [source] Chronic Alcohol Consumption Disrupted Cholesterol Homeostasis in Rats: Down-Regulation of Low-Density Lipoprotein Receptor and Enhancement of Cholesterol Biosynthesis Pathway in the LiverALCOHOLISM, Issue 3 2010Zhigang Wang Background:, Chronic alcohol consumption causes alcoholic liver disease, which is associated, or initiated, with dysregulated lipid metabolism. Very recent evidence suggested that dysregulated cholesterol metabolism plays an important role in the pathogenesis of alcoholic fatty liver diseases, however, the effects of chronic alcohol exposure on cholesterol homeostasis have not been well studied and underlying mechanisms behind are still elusive. Methods:, Male Sprague,Dawley rats weighing 250 ± 5.5 g (mean ± SEM) divided into 2 groups (8 rats per group) and pair-fed with liquid diets containing (in percent of energy intake) 18% protein, 35% fat, 12% carbohydrate, and 35% either ethanol (ethanol diet) or an isocaloric maltose-dextrin mixture (control diet), according to Lieber and De Carli, for 4 weeks. Results:, Long-term excessive alcohol feeding to rats caused fatty liver and liver injury, which was associated with disrupted cholesterol homeostasis, characterized by increased hepatic cholesterol levels and hypercholesterolemia. Hepatic cholesterol increases were concomitant with constantly activated sterol regulatory element-binding protein-2 (SREBP-2) in the liver and increased expression of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, a rate-limiting enzyme for cholesterol de novo synthesis, indicating enhanced cholesterol biosynthesis. Alcohol-induced hypercholesterolemia was accompanied by decreased LDL receptor (LDLr) levels in the liver. Further investigations revealed that chronic alcohol exposure increased hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) contents to down-regulate LDLr via a post-translational mechanism. Moreover, alcohol feeding suppressed extracellular signal-regulated kinase (ERK) activation in the liver. In vitro studies showed that inhibition of ERK activation was associated with decreased LDLr expression in HepG2 cells. Conclusions:, Our study provides the first evidence that both increased PCSK9 expression and suppressed ERK activation in the liver contributes to alcohol-induced hypercholesterolemia in rats. [source] Molecular Mechanisms of Alcoholic Fatty LiverALCOHOLISM, Issue 2 2009Vishnudutt Purohit Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. Alcohol exposure may induce fatty liver by increasing NADH/NAD+ ratio, increasing sterol regulatory element-binding protein-1 (SREBP-1) activity, decreasing peroxisome proliferator-activated receptor-, (PPAR-,) activity, and increasing complement C3 hepatic levels. Alcohol may increase SREBP-1 activity by decreasing the activities of AMP-activated protein kinase and sirtuin-1. Tumor necrosis factor-, (TNF-,) produced in response to alcohol exposure may cause fatty liver by up-regulating SREBP-1 activity, whereas betaine and pioglitazone may attenuate fatty liver by down-regulating SREBP-1 activity. PPAR-, agonists have potentials to attenuate alcoholic fatty liver. Adiponectin and interleukin-6 may attenuate alcoholic fatty liver by up-regulating PPAR-, and insulin signaling pathways while down-regulating SREBP-1 activity and suppressing TNF-, production. Recent studies show that paracrine activation of hepatic cannabinoid receptor 1 by hepatic stellate cell-derived endocannabinoids also contributes to the development of alcoholic fatty liver. Furthermore, oxidative modifications and inactivation of the enzymes involved in the mitochondrial and/or peroxisomal ,-oxidation of fatty acids could contribute to fat accumulation in the liver. [source] Alcohol-Induced Disruption of Endocrine SignalingALCOHOLISM, Issue 8 2007Martin J. J. Ronis This article contains the proceedings of a symposium at the 2006 ISBRA Meeting in Sydney Australia, organized and cochaired by Martin J. Ronis and Thomas M. Badger. The presentations were (1) Effect of Long-Term Ethanol Consumption on Liver Injury and Repair, by Jack R. Wands; (2) Alcohol-Induced Insulin Resistance in Liver: Potential Roles in Regulation of ADH Expression, Ethanol Clearance, and Alcoholic Liver Disease, by Thomas M. Badger; (3) Chronic Gestational Exposure to Ethanol Causes Brain Insulin and Insulin-Like Growth Factor Resistance, by Suzanne M de la Monte; (4) Disruption of IGF-1 Signaling in Muscle: A Mechanism Underlying Alcoholic Myopathy, by Charles H. Lang; (5) The Role of Reduced Plasma Estradiol and Impaired Estrogen Signaling in Alcohol-Induced Bone Loss, by Martin J. Ronis; and (6) Short-Term Influence of Alcohol on Appetite-Regulating Hormones in Man, by Jan Calissendorff. [source] Aldehyde Dehydrogenase 2 Gene Targeting Mouse Lacking Enzyme Activity Shows High Acetaldehyde Level in Blood, Brain, and Liver after Ethanol GavagesALCOHOLISM, Issue 11 2005Toyohi Isse Abstract: Background: Previously, we created an aldehyde dehydrogenase 2 gene transgenic (Aldh2,/,) mouse as an aldehyde dehydrogenase (ALDH) 2 inactive human model and demonstrated low alcohol preference. In addition, after a free-choice drinking test, no difference in the acetaldehyde level was observed between the Aldh2,/, and wild type (Aldh2+/+) mice. The actual amounts of free-choice drinking were so low that it is uncertain whether these levels are pharmacologically and/or behaviorally relevant in either strain. To elucidate this uncertainty, we compared the ethanol and acetaldehyde concentration in the blood, brain, and liver between the Aldh2,/, and Aldh2+/+ mice after ethanol gavages at the same dose and time. Method: We measured differences in the ethanol and acetaldehyde levels between the Aldh2,/, and Aldh2+/+ mice by headspace gas chromatography-mass spectrometry (GC-MS) after ethanol gavages at the same dose and time. Results: Significantly higher blood acetaldehyde concentrations were found in the Aldh2,/, mice than in the Aldh2+/+ mice 1 hr after the administration of ethanol gavages at doses of 0.5, 1.0, 2.0, and 5.0 g/kg. The blood acetaldehyde concentrations in the two strains were 2.4 vs. 0.5, 17.8 vs. 1.9, 108.3 vs. 4.3, and 247.2 vs. 14.0 (,M), respectively. In contrast, no significant difference was observed in the blood ethanol concentrations between the Aldh2+/+ and Aldh2,/, mice. The aldehyde dehydrogenase 2 enzyme metabolized 94% of the acetaldehyde produced from the ethanol as calculated from the area under the curve (AUC) of acetaldehyde when ethanol was administered at a dose of 5.0 g/kg. Conclusions: These data indicate that mouse ALDH2 is a major enzyme for acetaldehyde metabolism, and the Aldh2,/, mice have significantly high acetaldehyde levels after ethanol gavages. [source] Development of Alcoholic Fatty Liver and Fibrosis in Rhesus Monkeys Fed a Low n-3 Fatty Acid DietALCOHOLISM, Issue 10 2004Robert J. Pawlosky Background: The amount and type of dietary fat seem to be important factors that modulate the development of alcohol-induced liver steatosis and fibrosis. Various alcohol-feeding studies in animals have been used to model some of the symptoms that occur in liver disease in humans. Methods: Rhesus monkeys (Macaca mulatta) were maintained on a diet that had a very low concentration of ,-linolenic acid and were given free access to an artificially sweetened 7% ethanol solution. Control and ethanol-consuming animals were maintained on a diet in which the linoleate content was adequate (1.4% of energy); however, ,-linoleate represented only 0.08% of energy. Liver specimens were obtained, and the fatty acid composition of the liver phospholipids, cholesterol esters, and triglycerides of the two groups were compared at 5 years and histopathology of tissue samples were compared at 3 and 5 years. Results: The mean consumption of ethanol for this group over a 5-year period was 2.4 g · kg,1· day,1. As a consequence of the ethanol-dietary treatment, there were significantly lower concentrations of several polyunsaturated fatty acids in the liver phospholipids of the alcohol-treated group, including arachidonic acid and most of the n-3 fatty acids and particularly docosahexaenoic acid, when compared with dietary controls. Liver specimens from animals in the ethanol group at 5 years showed a marked degree of steatosis, both focal and diffuse cellular necrosis, and an increase in the development of fibrosis compared with specimens obtained at 3 years and with those from dietary controls, in which there was no evidence of fibrotic lesions. Conclusion: These findings suggest that the advancement of ethanol-induced liver disease in rhesus monkeys may be modulated by the amount and type of dietary essential fatty acids and that a marginal intake of n-3 fatty acids may be a permissive factor in the development of liver disease in primates. [source] Optimum Dietary Level of L-ascorbic Acid for Japanese Eel, Anguilla japonicaJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 4 2005Toncaun Ren A feeding experiment was conducted to determine the optimum dietary level of ascorbic acid (AsA) for Japanese eel juveniles using L-ascorbic acid Ca based on growth, AsA content in tissues, hematology, and bactericidal activity of serum with Escherichia coli. Test diets with six levels of AsA (3, 10, 27,126, 645, and 3,135-mg/kg diet) as Ca ascorbate were fed to juvenile Japanese eels (11.0 ± 0.2 g) once a day for 8 wk. High survival rates (> 80%) were observed among all dietary treatment groups. The specific growth rates of the fish fed diets containing 3 and 10-mg AsA/kg were significantly (P < 0.05) lower than those of other groups. Liver and brain AsA contents of the fish fed diets containing 3, 10, and 27-mg AsA/kg were significantly (P < 0.05) lower than those of the fish fed diets containing 645 and 3,135-mg AsA/kg. Hemoglobin content tended to be higher in the fish fed diets containing 645 and 3,135-mg AsA/kg than those of the fish fed other diets. Hematocrit value and total serum protein content of the fish fed diets containing 645 and 3135 mg AsA/kg were significantly (P < 0.05) higher than those of the other groups. The fish fed diets containing more than 27-mg AsAlkg showed a higher bactericidal activity of serum than the fish fed the diets containing 3-mg and 10-mg AsA/kg. The optimum dietary level of AsA for the Japanese eel juveniles growth was estimated to be more than 27-mg AsA/kg. Furthermore, the inclusion of 645-mg AsA/kg or more also increased the hematocrit, hemoglobin, total serum protein value, and liver and brain vitamin C concentrations. [source] Review article: the diagnosis and management of alcoholic hepatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009S. M. COHEN Summary Background, Alcoholic hepatitis is a severe, cholestatic liver disease occurring in patients with alcohol abuse. Mortality is substantial; however, therapies may improve clinical outcomes. Aim, To provide an updated review of the epidemiology, diagnosis, staging and treatment of alcoholic hepatitis. Methods, A MEDLINE literature search was performed to identify pertinent articles. Relevant clinical abstracts were also reviewed. Results, Severe alcoholic hepatitis occurs in a small fraction of patients who abuse alcohol. The 28-day mortality ranges from 30% to 50% in most series. Diagnosis is generally based on clinical features, with a limited role for liver biopsy. Beneficial treatment options include alcohol abstinence and nutritional therapy. Despite variable results in clinical trials, corticosteroids and pentoxifylline appear to provide moderate survival benefit. Anti-tumour necrosis factor agents and antioxidants have not proven beneficial, and should be limited to clinical trials. Liver transplant is not a frequent option given the active or recent alcohol use. Conclusions, Severe alcoholic hepatitis is a clinically-diagnosed condition associated with significant mortality. Alcohol abstinence and nutritional therapy have been associated with improved clinical parameters and should be considered in all patients. Corticosteroid therapy and pentoxifylline therapy appear to show moderate survival benefit and should be considered as first-line therapeutic agents. [source] Liver test patterns in patients with acute calculous cholecystitis and/or choledocholithiasisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009M. S. PADDA Summary Background, Liver tests are utilized to determine the presence of biliary obstruction. Aim, To examine our hypothesis that liver tests aid in elucidating whether patients have simple calculous cholecystitis (ACC) or choledocholithiasis (CDL). Methods, We performed a retrospective study of patients admitted to two University of Texas Southwestern teaching hospitals with a clinical picture consistent with ,acute gallstone disease', i.e. cholecystitis ± choledocolithiasis. The presence of ACC and CDL was based on defined clinical criteria. Results, The cohort consisted of 154 patients meeting specific entry criteria, primarily with right upper quadrant pain; 62 ACC, 79 both ACC and CDL and 13 CDL alone. Approximately 30% of patients with ACC had abnormal alkaline phosphatase (ALP) and/or bilirubin level and approximately 50% had abnormal aminotransferase levels. Among patients with ACC/CDL, 77% had abnormal ALP, 60% had abnormal bilirubin and 90% had abnormal aminotransferase levels. By multivariate analysis, increasing common bile duct size and an abnormal ALP and alanine aminotransferase (ALT) were excellent predictors of having ACC with CDL. Conclusions, Liver test patterns can aid in elucidating CDL, including in ACC patients. Fundamentally, patients with CDL were more likely to have more abnormal liver tests, whether they had CDL only, or CDL and ACC. A dilated CBD, and abnormal ALP and ALT had modest sensitivity and high specificity for identification of patients with ACC and CDL. [source] Review article: multimodality treatment of liver metastases increases suitability for surgical treatmentALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2007K. P. DE JONG Summary Background Liver metastases of colorectal cancer occur frequently, but only 10,20% are eligible for liver surgery. Recent new developments changed the concepts of treating patients with colorectal liver metastases. Aim To describe the available modalities that can result in increasing resectability rate. Methods Potentials and drawbacks of portal vein embolization, radiofrequency ablation (RFA), trans-ablated tumour hepatectomy, neoadjuvant chemotherapy and the approach to patients with extrahepatic metastases are described. Results Portal vein embolization is a well-established technique to increase the volume of the future liver remnant. RFA should be applied if partial liver resection alone cannot make the liver tumour-free. Neoadjuvant chemotherapy in patients with unresectable liver metastases can result in secondary resectability rates of 15,40%. Hepatotoxicity can lead to a higher complication rate after partial liver resection. A limited number of extrahepatic tumour localizations should be resected as well. Conclusions A more aggressive approach to patients with colorectal liver metastases improves resectability rate and survival. Unfortunately, these new options have not been thoroughly evaluated in randomized controlled trials. For some of these modalities, the currently available results are so promising that it might be difficult to start such trials in the future. [source] Role of circulating neurotoxins in the pathogenesis of hepatic encephalopathy: potential for improvement following their removal by liver assist devicesLIVER INTERNATIONAL, Issue 2003Roger F. Butterworth Abstract Both acute and chronic liver failure result in impaired cerebral function known as hepatic encephalopathy (HE). Evidence suggests that HE is the consequence of the accumulation in brain of neurotoxic and/or neuroactive substance including ammonia, manganese, aromatic amino acids, mercaptans, phenols, short-chain fatty acids, bilirubin and a variety of neuroactive medications prescribed as sedatives to patients with liver failure. Brain ammonia concentrations may attain levels in excess of 2 mm, concentrations which are known to adversely affect both excitatory and inhibitory neurotransmission as well as brain energy metabolism. Manganese exerts toxic effects on dopaminergic neurones. Prevention and treatment of HE continues to rely heavily on the reduction of circulating ammonia either by reduction of gut production using lactulose or antibiotics or by increasing its metabolism using l -ornithine- l -aspartate. No specific therapies have so far been designed to reduce circulating concentrations of other toxins. Liver assist devices offer a potential new approach to the reduction of circulating neurotoxins generated in liver failure. In this regard, the Molecular Absorbents Recirculating System (MARS) appears to offer distinct advantages over hepatocyte-based systems. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||