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Liver Tissue (liver + tissue)
Kinds of Liver Tissue Terms modified by Liver Tissue Selected AbstractsDetection of Helicobacter ganmani -Like 16S rDNA in Pediatric Liver TissueHELICOBACTER, Issue 5 2004Vasundhara Tolia ABSTRACT Background., To determine the presence of Helicobacter species in the liver biopsy specimens from children with various chronic liver diseases as data in adult literature suggests a possible role of these bacteria in their pathogenesis. Materials and methods., Paraffin sections of 61 liver biopsies of pediatric patients with miscellaneous diseases and autopsy liver tissue from 10 control subjects with no evidence of preexisting liver disease were examined for the presence of Helicobacter species by a genus-specific seminested polymerase chain reaction (PCR) assay. PCR,products of positive samples were further characterized by denaturing gradient gel electrophoresis (DGGE) and DNA-sequence analysis. Based on those results, a seminested PCR assay for H. ganmani was developed and applied to the samples. Results., On analysis, 40/61 patient samples were positive in the genus-specific Helicobacter PCR and 4/10 from the control group. The nucleotide sequences of 16S rDNA fragments were 99,100% similar to mainly Helicobacter sp. ,liver' and H. ganmani. PCR-products similar to H. canis and H. bilis were also found. The 16S rDNAs of control specimens showed similarity to Helicobacter sp. ,liver'. In the H. ganmani -specific PCR analysis 19 patients, but none of the controls, were positive. Conclusions., Amplified Helicobacter 16S rDNAs were related to Helicobacter sp. ,liver' or H. ganmani in liver biopsy specimens of pediatric patients. The possible significance of Helicobacter species in pediatric liver diseases needs to be evaluated further in prospective studies. [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] Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infectionJOURNAL OF MEDICAL VIROLOGY, Issue 2 2002P. Trimoulet Abstract Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads,<,10,000 copies/ml, CD4+ count,>,250/,l. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r,=,0.47; P,=,0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4+, HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r,=,0.52; P,=,0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P,=,0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P,=,0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration. J. Med. Virol. 67:143,151, 2002. © 2002 Wiley-Liss, Inc. [source] Lack of susceptibility of Chacma baboons (Papio ursinus orientalis) to hepatitis C virus infectionJOURNAL OF MEDICAL VIROLOGY, Issue 4 2002N.P. Sithebe Abstract The main reason to ascertain whether baboons are susceptible to infection with hepatitis C virus (HCV) is the need to replace chimpanzees, which are endangered, as an animal model for undertaking research into the biology and host,virus interactions of HCV, and for developing a vaccine against this virus. A second reason is that baboons are a possible source of xenografts for human liver transplantation. We inoculated serum containing HCV into four Chacma baboons and monitored them for 52 weeks for evidence of infection. Serum was tested for antibody to HCV, HCV RNA, and aminotransferase concentrations at 2-week intervals for 26 weeks and thereafter at 4-week intervals. Liver tissue was examined at 28 and 52 weeks for histopathological changes and viral RNA, and at 52 weeks for viral particles using electron microscopy. Reverse transcription-polymerase chain reaction assay was used to detect HCV RNA, and the results were confirmed by Southern hybridization. Serum aminotransferase concentrations remained within the normal range and liver histology was normal during the follow-up period. Passive transmission of anti-HCV to the baboons was observed during the first 4 weeks. HCV RNA was not detectable in any serum or liver sample and electron microscopy failed to reveal viral particles in liver tissue. In conclusion, we did not find Chacma baboons to be susceptible to infection with HCV, although we cannot deny that in an immunosuppressed liver transplant recipient, infection of a baboon xenograft might occur. Another animal model for HCV infection must be sought. J. Med. Virol. 66:468,471, 2002. © 2002 Wiley-Liss, Inc. [source] Intrahepatic expression of the hepatic stellate cell marker fibroblast activation protein correlates with the degree of fibrosis in hepatitis C virus infectionLIVER INTERNATIONAL, Issue 2 2002MT Levy Abstract: Background: Activated hepatic stellate cells (HSCs), recognised by their , smooth muscle actin immunoreactivity, are primarily responsible for liver fibrosis. However, the presence of , smooth muscle actin positive HSCs is not always associated with the development of liver fibrosis. Recently, other markers of human HSCs including the gelatinase fibroblast activation protein (FAP) and glial fibrillary acidic protein have been identified. Aims: We examined the relationship between the expression of these HSC markers and the severity of liver injury in patients with chronic hepatitis C virus infection. Methods: Liver tissue from 27 patients was examined using immunohistochemistry. Linear correlation analysis was used to compare staining scores with the stage and grade of liver injury. Results,Conclusions: FAP expression, seen at the tissue-remodelling interface, was strongly and significantly correlated with the severity of liver fibrosis. A weaker correlation was seen between glial fibrillary acidic protein expression and fibrosis stage. This contrasted with the absence of a relationship between , smooth muscle actin and the fibrotic score. A correlation was also observed between FAP expression and necroinflammatory score. In summary, FAP expression identifies a HSC subpopulation at the tissue-remodelling interface that is related to the severity of liver fibrosis. [source] Transthyretin-derived amyloid deposition on the gastric mucosa in domino recipients of familial amyloid polyneuropathy liverLIVER TRANSPLANTATION, Issue 2 2007Yo-ichi Takei Familial amyloid polyneuropathy (FAP) is a form of hereditary generalized amyloidosis. Liver tissue explanted from FAP patients has normal structure and function, except for the production of amyloidogenic variant transthyretin (TTR), and domino liver transplantation (DLT) using grafts from FAP patients was first performed in 1995. FAP symptoms usually develop in genetically determined individuals after the age of 20, but it is difficult to estimate when FAP symptoms will appear in domino recipients. Concerning this problem, histological findings showing amyloid deposition have recently been obtained in a few domino recipients of FAP livers. This study investigated the presence of de novo amyloid deposition in the gastroduodenal mucosa of domino recipients transplanted at our institution. Biopsy of gastroduodenal mucosa was carried out in 5 recipients of FAP livers and TTR-derived amyloid deposits were detected in 2 patients, both of whom had undergone DLT 47 months previously. In FAP liver recipients, de novo systemic amyloid deposition may begin much sooner than previously supposed. Therefore, careful follow-up of domino recipients of FAP livers is required. Liver Transpl, 2006. © 2006 AASLD. [source] FTY720 Attenuates Hepatic Ischemia-Reperfusion Injury in Normal and Cirrhotic LiversAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2005Kwan Man Hepatic ischemia-reperfusion injury is an inevitable consequence during liver surgery. The outcome is particularly poor in cirrhotic livers, which are more prone to hepatic ischemia-reperfusion injury. We aim to study whether FTY720 could attenuate hepatic ischemia-reperfusion injury both in normal and in cirrhotic livers. We applied a 70% liver-ischemia (60 min) model in rats with normal or cirrhotic livers. FTY720 was given 20 min before ischemia and 10 min before reperfusion (1 mg/kg, i.v.). Liver tissues and blood were sampled at 20 min, 60 min, 90 min, 6 h and 24 h after reperfusion for detection of MAPK-Egr-1, Akt pathways and caspase cascade. Hepatic ultrastructure and apoptosis were also compared. FTY720 significantly improved liver function in the rats with normal and cirrhotic livers. Akt pathway was activated at 6 and 24 h after reperfusion. FTY720 significantly down-regulated Egr-1, ET-1, iNOS and MIP-2 accompanied with up-regulation of A20, IL-10, HO-1 and Hsp70. MAPK (Raf-MEK-Erk) pathway was down-regulated. Hepatic ultrastructure was well maintained and fewer apoptotic liver cells were found in the FTY720 groups. In conclusion, FTY720 attenuates ischemia-reperfusion injury in both normal and cirrhotic livers by activation of cell survival Akt signaling and down-regulation of Egr-1 via Raf-MEK-Erk pathway. [source] Effects of varying dietary fatty acid profile on growth performance, fatty acid, body and tissue composition of juvenile pike perch (Sander lucioperca)AQUACULTURE NUTRITION, Issue 6 2005C. SCHULZ Abstract Pike perch (Sander lucioperca) has been identified as specie destined to diverse European inland aquaculture, but knowledge on the nutritional requirements is weak. Therefore, we investigated the effect of varying dietary fatty acid (FA) profile by partial replacement of fish oil (FO) with vegetable oils on growth, FA and body composition of juvenile pike perch. An extruded basal diet containing 59 g kg,1 crude lipids (FO) was added with 60 g kg,1 FO, 60 g kg,1 linseed oil (LO) or 60 g kg,1 soybean oil (SO). The resulting dietary FA composition differed mainly in the triglyceride fraction and was characterized by highest amounts of linolenic acid (18:3 n-3) in the LO diet and linoleic acid in the SO diet. Diet enriched with FO contained highest contents of highly unsaturated FA 20:5 n-3 (eicosapentaenic acid) and 22:6 n-3 (docosahexaenic acid). Pike perch were held in a recirculation system and each feeding group (in triplicate) was fed with experimental diets at a daily rate of 35 g kg,1 of biomass for 57 days by automatic feeders. Weight gain and specific growth rate of experimental feeding groups ranged between 18.47 and 19.58 g and 1.37,1.45% day,1 and was not affected by the dietary composition indicating that FO can be replaced by vegetable oils without negative impact on growth performance. In contrast to the whole body and muscle composition, liver tissue was affected by the varying diets. Liver tissues of fish fed diets enriched with vegetable oils showed significantly increased lipid contents of 162 (LO) and 147 (SO) g kg,1 and indicate decreased lipid utilization compared with fish fed FO diet (liver lipid content 112 g kg,1). Nevertheless, hepatosomatic index of pike perch was not influenced by dietary lipid composition. The FA profile of pike perch was generally determined by the dietary FAs. [source] Establishment of a chick embryo model for analyzing liver development and a search for candidate genesDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 6 2005Yuji Yokouchi The liver plays a crucial role in metabolism. There is considerable interest in how the liver develops, as such knowledge could prove of importance in regenerative medicine. However, our understanding of liver development remains somewhat limited. We have developed a model system using the chick embryo that is cost effective and is easy to manipulate experimentally. We performed four fundamental studies: (i) construction of an atlas of the developing chick liver; (ii) identification of differentiation marker genes in the developing chick embryo; (iii) development of germ-layer specific electroporation; and (iv) establishment of organ culture from the developing chick liver. Using this system, we have been able to demonstrate the functions of candidate genes within a shorter period and in a more cost-effective manner. In parallel with the establishment of this system, we examined the expression patterns of genes known to be required for organ development in the developing chick embryo in order to identify genes also involved in liver development. To date, we have found sixteen genes that are expressed in the developing chick liver (GELD, genes expressed in liver development). This knowledge will be fundamental to the establishment of the basic technology for engineering liver tissue in the future. [source] New supported liquid membrane-capillary electrophoresis in-line arrangement for direct selective analysis of complex samplesELECTROPHORESIS, Issue 15 2006Leonor Nozal Abstract An in-line coupling of a micro-membrane extraction unit, based on supported liquid membrane, with commercially available capillary electrophoresis equipment is described. A main characteristic of this micro-membrane device, made from a simple Eppendorf tube, is that it permits the application of voltage in the acceptor solution to be applied during the extraction process. This has been shown as an alternative to enhance sensitivity, as the analytical signal achieved by applying 10,kV for 20,min was similar to that obtained without the application of voltage and with extraction time of 60,min. In addition, the design has been made permitting both in-line hydrodynamic and electrokinetic sample introduction into the electrophoretic capillary. The analytical potential of the proposed system has been demonstrated by the direct determination of nitroimidazoles from pig liver tissue. The high efficiency of the proposed system allowed the extraction and the determination of the analytes to be performed from a simple tissue homogenate obtained in water. The precision of the analysis of spiked samples, expressed in terms of relative standard deviation, was better than 4.8%. [source] Histopathological alterations in the liver of the sharptooth catfish Clarias gariepinus from polluted aquatic systems in South AfricaENVIRONMENTAL TOXICOLOGY, Issue 2 2009M. J. Marchand Abstract There is a need for sensitive bio-monitoring tools in toxicant impact assessment to indicate the effect of toxicants on fish health in polluted aquatic ecosystems. Histopathological assessment of fish tissue allows for early warning signs of disease and detection of long-term injury in cells, tissues, or organs. The aim of this study was to assess the degree of histopathological alterations in the liver of C. gariepinus from two dams in an urban nature reserve, (Gauteng, South Africa). Two dams (Dam 1 and Dam 2) were chosen for their suspected levels of toxicants. Water and sediments were sampled for metal and potential endocrine disrupting chemical analysis. A quantitative and qualitative histology-based health assessment protocol was employed to determine the adverse health effects in fish. The analysis of blood constituents, fish necropsy, calculation of condition factors, and hepatosomatic indices were employed to support the findings of the qualitative and quantitative histological assessment of liver tissue. Assessment of the liver tissue revealed marked histopathological alterations including: structural alterations (hepatic cord disarray) affecting 27% of field specimens; plasma alterations (granular degeneration 98% and fatty degeneration 25%) of hepatocytes; an increase in melanomacrophage centers (32%); hepatocyte nuclear alterations (90%); and necrosis of liver tissue (14%). The quantitative histological assessment indicated that livers of fish collected from Dam 1 were more affected than the fish livers collected from Dam 2. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009. [source] Detection of nodularin in flounders and cod from the Baltic SeaENVIRONMENTAL TOXICOLOGY, Issue 2 2001Vesa Sipiä Abstract The brackish water cyanobacterium Nodularia spumigena regularly forms waterblooms in the Baltic Sea. Many N. spumigena strains can produce nodularin, a hepatotoxic penta-peptide, which has caused several animal poisonings in the Baltic Sea area. To improve our understanding of nodularin bioaccumulation in aquatic organisms this study measured nodularin in flounder and cod caught from the Baltic Sea. Flounders were collected from the western Gulf of Finland in July 1996, September 1997, and September 1998, and from the Gulf of Bothnia in August 1997 and September 1998. Flounders were also collected from the coastal areas of Sweden in the Baltic Proper during September 1998. Cod were caught from the southern Baltic Sea in August 1998. Livers and muscles of the 1997 fish were isolated, extracted, and analysed for nodularin using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) and protein phosphatase 1 (PP1) inhibition assay. Approximately 30,70 ng of nodularin/g dry weight (maximum value 140 ng/g) were found in the liver tissue samples by ELISA and PP1 inhibition. These concentrations were below the detection limit of HPLC. PP1 assay showed inhibition also in muscle samples, but this may due to other compounds present in the muscle extracts rather than NODLN or due to matrix interference. The recovery of nodularin from liver tissue with ELISA and PP1 assays was about 30%. Nodularin concentrations in samples are not corrected for recovery. Although the concentrations of nodularin found in this study are low further studies of nodularin are needed to assess possible bioaccumulation in brackish water food webs. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 121,126, 2001 [source] The effect of food rations on tissue-specific copper accumulation patterns of sublethal waterborne exposure in Cyprinus carpioENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2007Shodja Hashemi Abstract Common carp (Cyprinus carpio) were fed to two different food rations, 0.5% body weight (low ration [LR]) and 5% body weight (high ration [HR]), and were exposed to sublethal (1 ,M) copper levels for 28 d in softened Antwerp (Belgium) city tap water (Ca2+, 79.3 mg/L; Mg2+, 7.4 mg/L; Na+, 27.8 mg/L; pH 7.5,8.0). Copper accumulations in the liver, gills, kidney, anterior intestine, posterior intestine, and muscle were determined. Copper accumulation in the gills, liver, and kidney of LR fish was significantly higher than in HR fish. The only time copper uptake in HR fish was significantly higher than in LR fish was in the posterior intestine after two weeks of exposure. No difference was found between the two rations in the anterior intestine. Copper accumulation in the liver of both feeding treatments occurred in a time-dependent manner and did not reach steady state in any treatment. On the contrary, copper concentration in the gills reached a steady state for both HR and LR fish within the first week of exposure. No copper accumulation was found in muscle tissues of either treatment. Copper concentration dropped to control levels in all tissues, except liver tissue, two weeks after the exposure ended. Our studies indicated that copper uptake was influenced by the food ration in carp. The difference in copper accumulation probably is related to the amount of dietary NaCl and different rates of metallothionein synthesis. Low food availability provides less Na+ influx and leads to increased brachial uptake of Na+ and copper. In addition, it has been shown that starved animals show increased levels of metallothionein, possibly causing higher copper accumulation. [source] NF,B, cytokines, TLR 3 and 7 expression in human end-stage HCV and alcoholic liver diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2010Peter Stärkel Eur J Clin Invest 2010; 40 (7): 575,584 Abstract Background/aims, Conflicting observations exist concerning the role of nuclear factor kappa B (NF,B) in alcoholic liver disease (ALD) in animal models. To date no studies have examined this aspect in human liver tissue. We here assessed cytokines and toll-like receptors (TLRs) expressions in conjunction with NF,B activation in non-active end-stage human ALD compared with normal livers and hepatitis C virus (HCV) related end-stage disease. Methods, mRNA and protein expression were examined by quantitative PCR and Western blotting, DNA-binding by electrophoretic mobility shift assays and NF,B sub-cellular localization by immunofluorescent staining of livers. Results, NF,B mRNA and protein expression as well as strong DNA-binding were preserved in ALD but significantly down-regulated in HCV compared with normal livers. P50 immunofluorescence was found in hepatocytes and bile ducts in ALD and normal livers, whereas a shift was observed in p65 staining from non-parenchymal cells in normal livers to hepatocytes in ALD. NF,B responsive genes mRNA levels IkB, and interleukin 6 were significantly higher in ALD compared with HCV. Tumour necrosis factor alpha (TNF,), TLRs 3 and 7 mRNA were up-regulated in ALD and HCV compared with normal liver with TNF, and TLR7 being the highest in HCV. Strong induction of interferon beta was found in HCV but not in ALD or normal liver tissue. Conclusions, Persistent NF,B activation together with high pro-inflammatory cytokine expression and upregulation of TLR3 and TLR7 is associated with end-stage ALD in humans and could contribute to disease progression even in absence of alcohol intake. [source] Establishment of a mouse xenograft model for mycosis fungoidesEXPERIMENTAL DERMATOLOGY, Issue 7 2004Sonja Thaler Abstract:, Mycosis fungoides (MF) is the most frequent variant of cutaneous T-cell lymphomas (CTCLs). MF primarily involves the skin initially with patches and plaques. In later stages, cutaneous tumors develop and tumor cells may spread to lymph nodes and finally to visceral sites. Here, we describe an animal model for MF in immune-deficient nude mice, using the CTCL cell line MyLa. Subcutaneous transplantation of MyLa cells leads to the formation of cutaneous tumors in 80% of the mice (50/60 total). Spread of tumor cells to visceral sites was detected by immunohistochemistry and polymerase chain reaction (PCR)-based detection of specific T-cell receptor-, rearrangement. MyLa cells were found circulating in the blood, lymph nodes, and in blood vessels of heart, kidney, lung, and liver. In lung and liver tissue, tumor cells presented perivascular invasion, but no large secondary tumors developed. The nude mouse model described here will be a valuable test system for new therapeutic approaches for the treatment of MF and opens the unique opportunity to study the disease in vivo. [source] Interpreting temporal variation in omnivore foraging ecology via stable isotope modellingFUNCTIONAL ECOLOGY, Issue 4 2009Carolyn M. Kurle Summary 1The use of stable carbon (C) and nitrogen (N) isotopes (,15N and ,13C, respectively) to delineate trophic patterns in wild animals is common in ecology. Their utility as a tool for interpreting temporal change in diet due to seasonality, migration, climate change or species invasion depends upon an understanding of the rates at which stable isotopes incorporate from diet into animal tissues. To best determine the foraging habits of invasive rats on island ecosystems and to illuminate the interpretation of wild omnivore diets in general, I investigated isotope incorporation rates of C and N in fur, liver, kidney, muscle, serum and red blood cells (RBC) from captive rats raised on a diet with low ,15N and ,13C values and switched to a diet with higher ,15N and ,13C values. 2I used the reaction progress variable method (RPVM), a linear fitting procedure, to estimate whether a single or multiple compartment model best described isotope turnover in each tissue. Small sample Akaike Information criterion (AICc) model comparison analysis indicated that 1 compartment nonlinear models best described isotope incorporation rates for liver, RBC, muscle, and fur, whereas 2 compartment nonlinear models were best for serum and kidney. 3I compared isotope incorporation rates using the RPVM versus nonlinear models. There were no differences in estimated isotope retention times between the model types for serum and kidney (except for N turnover in kidney from females). Isotope incorporation took longer when estimated using the nonlinear models for RBC, muscle, and fur, but was shorter for liver tissue. 4There were no statistical differences between sexes in the isotope incorporation rates. I also found that N and C isotope incorporation rates were decoupled for liver, with C incorporating into liver tissue faster than N. 5The data demonstrate the utility of analysing isotope ratios of multiple tissues from a single animal when estimating temporal variation in mammalian foraging ecology. [source] Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in miceFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2009C. Girish Abstract Oxidative stress is implicated as a common pathologic mechanism contributing to the initiation and progression of hepatic damage in a variety of liver disorders. Present study attempts to evaluate the hepatoprotective activity of picroliv, curcumin and ellagic acid in comparison to silymarin using paracetamol (PCM) induced acute liver damage. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg) and was assessed by quantifying the serum enzyme activities, phenobarbitone induced sleeping time and histopathological analysis of liver tissues. The antioxidant parameters, malondialdehyde (MDA), reduced glutathione (GSH) and catalase of the liver tissue were also assessed. The herbal drugs were administered for 7 days by oral route at 50 and 100 mg/kg. PCM induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (alanine transaminase, aspartate transaminase and alkaline phosphatase) in serum and MDA level in liver. There was also a significant decrease in activity of GSH and catalase levels. The histopathological examination on toxic models revealed centrizonal necrosis and fatty changes. Pretreatment of mice with picroliv, curcumin and ellagic acid reversed these altered parameters towards normal values, which were compared with silymarin. The normalization of phenobarbitone induced sleeping time suggests the restoration of liver cytochrome P450 enzymes. This study supports the use of these active phytochemicals against toxic liver injury, which may act by preventing the lipid peroxidation and augmenting the antioxidant defense system or regeneration of hepatocytes. These active phytochemicals may be developed as drugs for the treatment of liver diseases. [source] Detection of Helicobacter ganmani -Like 16S rDNA in Pediatric Liver TissueHELICOBACTER, Issue 5 2004Vasundhara Tolia ABSTRACT Background., To determine the presence of Helicobacter species in the liver biopsy specimens from children with various chronic liver diseases as data in adult literature suggests a possible role of these bacteria in their pathogenesis. Materials and methods., Paraffin sections of 61 liver biopsies of pediatric patients with miscellaneous diseases and autopsy liver tissue from 10 control subjects with no evidence of preexisting liver disease were examined for the presence of Helicobacter species by a genus-specific seminested polymerase chain reaction (PCR) assay. PCR,products of positive samples were further characterized by denaturing gradient gel electrophoresis (DGGE) and DNA-sequence analysis. Based on those results, a seminested PCR assay for H. ganmani was developed and applied to the samples. Results., On analysis, 40/61 patient samples were positive in the genus-specific Helicobacter PCR and 4/10 from the control group. The nucleotide sequences of 16S rDNA fragments were 99,100% similar to mainly Helicobacter sp. ,liver' and H. ganmani. PCR-products similar to H. canis and H. bilis were also found. The 16S rDNAs of control specimens showed similarity to Helicobacter sp. ,liver'. In the H. ganmani -specific PCR analysis 19 patients, but none of the controls, were positive. Conclusions., Amplified Helicobacter 16S rDNAs were related to Helicobacter sp. ,liver' or H. ganmani in liver biopsy specimens of pediatric patients. The possible significance of Helicobacter species in pediatric liver diseases needs to be evaluated further in prospective studies. [source] The amazing universe of hepatic microstructure,HEPATOLOGY, Issue 2 2009Valeer J. Desmet An informal review is presented by the author of his 50 years of involvement in practice and research in hepatopathology. Some background for the author's attitude and meandering pathway into his professional career serves as introduction to a short discussion of the main topics of his interest and expertise. Histogenesis of liver cancer was the theme of early work for a Ph.D. thesis, the results of which were lost into oblivion due to local rules and circumstances, but were rescued three decades later. His conclusions about the cells of origin of liver cancer remain concordant with the newer concepts in the field after nearly half a century. Studies in the field of chronic hepatitis became a long saga, involving the first classification of this syndrome by "the Gnomes" in 1968, histochemical investigations of viral antigens, lymphocyte subsets and adhesion molecules, and a quarter century later, the creation of a new classification presently in use. Cholestasis was a broadening field in diagnostic entities and involved the study of liver lesions, comprising pathways of bile regurgitation (including reversed secretory polarity of hepatocytes) and so-called ductular reaction. The latter topic has a high importance for the various roles it plays in modulating liver tissue of chronic cholestasis into biliary cirrhosis, and as the territory of hepatic progenitor cells, crucial for liver regeneration in adverse conditions and in development of liver cancer. Study of the embryology of intrahepatic bile ducts helped to clarify the strange appearance of the ducts in "ductal plate configuration" in several conditions, including some forms of biliary atresia with poor prognosis and all varieties of fibrocystic bile duct diseases with "ductal plate malformation" as the basic morphologic lesion. (HEPATOLOGY 2009;50:333,344.) [source] In vitro proton magnetic resonance spectroscopy of liver tissue informs in vivo hepatic proton magnetic resonance spectroscopy studies,HEPATOLOGY, Issue 3 2008Jeremy F.L. Cobbold No abstract is available for this article. [source] Impaired liver regeneration and increased oval cell numbers following T cell,mediated hepatitis,HEPATOLOGY, Issue 1 2007Ian N. Hines The regeneration of liver tissue following transplantation is often complicated by inflammation and tissue damage induced by a number of factors, including ischemia and reperfusion injury and immune reactions to the donor tissue. The purpose of the current study is to characterize the effects of T cell,mediated hepatitis induced by concanavalin A (ConA) on the regenerative response in vivo. Liver regeneration following a partial (70%) hepatectomy (pHx) was associated with elevations in serum enzymes and the induction of key cell cycle proteins (cyclin D, cyclin E, and Stat3) and hepatocyte proliferation. The induction of T cell,mediated hepatitis 4 days before pHx increased serum enzymes 48 hours after pHx, reduced early cyclin D expression and Stat3 activation, and suppressed hepatocyte proliferation. This inhibition of proliferation was also associated with increased expression of p21, the activation of Smad2, the induction of transforming growth factor beta and interferon gamma expression, and reduced hepatic interleukin 6 production. Moreover, the ConA pretreatment increased the numbers of separate oval cell-like CD117+ cells and hematopoietic-like Sca-1+ cell populations 48 hours following pHx. The depletion of natural killer (NK) cells, an important component of the innate immune response, did not affect liver injury or ConA-induced impairment of hepatocyte proliferation but did increase the numbers of both CD117-positive and Sca-1,positive cell populations. Finally, splenocytes isolated from ConA-pretreated mice exerted cytotoxicity toward autologous bone marrow cells in an NK cell,dependent manner. Conclusion: T cell,mediated hepatitis alters early cytokine responses, reduces hepatocellular regeneration, and induces NK cell,sensitive oval cell and hematopoietic-like cell expansion following pHx. (HEPATOLOGY 2007;46:229,241.) [source] Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C,HEPATOLOGY, Issue 5 2006Masao Honda The clinical manifestations of chronic hepatitis B (CH-B) and chronic hepatitis C (CH-C) are different. We previously reported differences in the gene expression profiles of liver tissue infected with CH-B or CH-C; however, the signaling pathways underlying each condition have yet to be clarified. Using a newly constructed cDNA microarray consisting of 9614 clones selected from 256,550 tags of hepatic serial analysis of gene expression (SAGE) libraries, we compared the gene expression profiles of liver tissue from 24 CH-B patients with those of 23 CH-C patients. Laser capture microdissection was used to isolate hepatocytes from liver lobules and infiltrating lymphoid cells from the portal area, from 16 patients, for gene expression analysis. Furthermore, the comprehensive gene network was analyzed using SAGE libraries of CH-B and CH-C. Supervised and nonsupervised learning methods revealed that gene expression was correlated more with the infecting virus than any other clinical parameters such as histological stage and disease activity. Pro-apoptotic and DNA repair responses were predominant in CH-B with p53 and 14-3-3 interacting genes having an important role. In contrast, inflammatory and anti-apoptotic phenotypes were predominant in CH-C. These differences would evoke different oncogenic factors in CH-B and CH-C. In conclusion, we describe the different signaling pathways induced in the livers of patients with CH-B or CH-C. The results might be useful in guiding therapeutic strategies to prevent the development of hepatocellular carcinoma in cases of CH-B and CH-C. (HEPATOLOGY 2006;44:1122,1138.) [source] An inhibitor of cyclin-dependent kinase, stress-induced p21Waf-1/Cip-1, mediates hepatocyte mito-inhibition during the evolution of cirrhosis,HEPATOLOGY, Issue 6 2005John G. Lunz III During the evolution of cirrhosis, there is a relative decrease in volume percentage of hepatocytes and a relative increase in biliary epithelial cells and myofibroblasts. This is recognized histopathologically as a ductular reaction and leads to gradual distortion of the normal hepatic architecture. The final or decompensated stage of cirrhosis is characterized by a further decline in hepatocyte proliferation and loss of functional liver mass that manifests clinically as ascites, encephalopathy, and other signs of liver failure. In this report, we tested the hypothesis that p21-mediated hepatocyte mito-inhibition accelerates the evolution of cirrhosis using an established mouse model of decompensated biliary cirrhosis, p21-deficient mice, and liver tissue from humans awaiting liver replacement. Despite the same insult of long-term (12-week) bile duct ligation, mice prone to decompensation showed significantly more oxidative stress and hepatocyte nuclear p21 expression, which resulted in less hepatocyte proliferation, an exaggerated ductular reaction, and more advanced disease compared with compensation-prone controls. Mice deficient in p21 were better able than wild-type controls to compensate for long-term bile duct ligation because of significantly greater hepatocyte proliferation, which led to a larger liver mass and less architectural distortion. Mito-inhibitory hepatocyte nuclear p21 expression in humans awaiting liver replacement directly correlated with pathological disease stage and model of end-stage liver disease scoring. In conclusion, stress-induced upregulation of hepatocyte p21 inhibits hepatocyte proliferation during the evolution of cirrhosis. These findings have implications for understanding the evolution of cirrhosis and associated carcinogenesis. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005.) [source] Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injuryHEPATOLOGY, Issue 5 2004Heike Bantel Chronic hepatitis C virus (HCV) infection is characterized by inflammatory liver damage and is associated with a high risk of development of cirrhosis and hepatocellular carcinoma. Although histological examination of liver biopsies is currently the gold standard for the detection of early liver damage, there is a strong need for better noninvasive methods. We recently demonstrated that the proapoptotic activation of caspases is considerably enhanced in histological sections from HCV-infected liver tissue, suggesting an important role of apoptosis in liver damage. Here, we investigated whether caspase activation is detectable also in sera from patients with chronic HCV infection. Using a novel enzyme-linked immunosorbent assay that selectively recognizes a proteolytic neoepitope of the caspase substrate cytokeratin-18, we demonstrate that caspase activity is markedly increased in the sera of HCV patients. Interestingly, while 27% of patients with chronic HCV infection showed normal aminotransferase levels despite inflammatory and fibrotic liver damage, more than 50% of those patients exhibited already elevated serum caspase activity. Moreover, 30% of patients with normal aminotransferase but elevated caspase activity revealed higher stages of fibrosis. In conclusion, compared with conventional surrogate markers such as aminotransferases, detection of caspase activity in serum might be a more sensitive method of detecting early liver injury. Thus, measurement of caspase activity might provide a novel diagnostic tool, especially for patients with normal aminotransferases but otherwise undiagnosed histologically active hepatitis and progressive fibrosis. (HEPATOLOGY 2004;40:1078,1087.) [source] Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinomaHEPATOLOGY, Issue 6 2004Christoph Jüngst Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory liver disease. 8-oxo-2,-deoxyguanosine (8-oxo-dG), the major promutagenic DNA adduct caused by reactive oxygen species (ROS), leads to G:C , T:A transversions. These lesions can be enzymatically repaired mainly by human MutT homolog 1 (hMTH1), human 8-oxo-guanine DNA glycosylase (hOGG1) and human MutY homolog (hMYH). The aim of this study was to evaluate the extent of oxidative damage and its dependence on the cellular antioxidative capacity and the expression of specific DNA repair enzymes in tumor (tu) and corresponding adjacent nontumor (ntu) liver tissue of 23 patients with histologically confirmed hepatocellular carcinoma. 8-oxo-dG levels, as detected by high-pressure liquid chromatography with electrochemical detection, were significantly (P = .003) elevated in ntu tissue (median, 129 fmol/,g DNA) as compared to tu tissue (median, 52 fmol/,g DNA), and were closely associated with inflammatory infiltration. In ntu tissue, the hepatic iron concentration and malondialdehyde levels were significantly (P = .001) higher as compared to tu tissue. Glutathione content, glutathione peroxidase activity and manganese superoxide dismutase messenger RNA (mRNA) expression did not show statistical differences between ntu and tu tissue. Real-time reverse transcription polymerase chain reaction revealed in tu tissue significantly (P = .014) higher hMTH1 mRNA expression compared to ntu tissue. In contrast, hMYH mRNA expression was significantly (P < .05) higher in ntu tissue. No difference in hOGG1 mRNA expression was seen between tu and ntu. In conclusion, these data suggest that ROS generated by chronic inflammation contribute to human hepatocarcinogenesis. The role of DNA repair enzymes appears to be of reactive rather than causative manner. (HEPATOLOGY 2004;39:1663,1672.) [source] Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitisHEPATOLOGY, Issue 4 2003M.D., Mercedes Pérez-Carreras Ph.D. Mitochondrial dysfunction might play a central role in the pathogenesis of nonalcoholic steatohepatits (NASH). The aims of this study were to evaluate whether free fatty acid (FFA) transport into the mitochondria or the activity of mitochondria respiratory chain (MRC) complexes are impaired in NASH. In patients with NASH and control subjects, we measured free carnitine, short-chain acylcarnitine (SCAC) and long-chain acylcarnitine (LCAC) esters, carnitine palmitoyltransferase (CPT) activity, and MRC enzyme activity in liver tissue as well as serum concentration of tumor necrosis factor , (TNF-,), homeostatic metabolic assessment of insulin resistance (HOMAIR), and body mass index (BMI). In patients with NASH, the LCAC/free carnitine ratio was significantly increased and the SCAC/free carnitine ratio was decreased. In patients with NASH, the activity of the MRC complexes was decreased to 63% ± 20% (complex I), 58.5% ± 16.7% (complex II), 70.6% ± 10.3% (complex III), 62.5% ± 13% (complex IV), and 42.4% ± 9.1% (adenosine triphosphate synthase) of the corresponding control values. Activity of these complexes correlated significantly with serum TNF-, and HOMAIR. Serum TNF-, (36.3 ± 23.1 pg/mL), HOMAIR (4.5 ± 2.38), and BMI (29.9 ± 3.5 kg/m2) values were significantly increased in patients with NASH. In conclusion, activities of MRC complexes were decreased in liver tissue of patients with NASH. This dysfunction correlated with serum TNF-,, insulin resistance, and BMI values. (Hepatology 2003;38:999,1007). [source] Prevention of diet-induced fatty liver in experimental animals by the oral administration of a fatty acid bile acid conjugate (FABAC)HEPATOLOGY, Issue 2 2003Tuvia Gilat Fatty acid bile acid conjugates (FABACs) are a new family of synthetic molecules designed to solubilize biliary cholesterol. They were shown to prevent and dissolve cholesterol gallstones in inbred C57L/J mice fed a lithogenic, high-fat diet (HFD). In these mice, fatty liver was observed in the controls but not in the FABAC-treated ones. The present study was designed to study the effect of FABAC (arachidyl-amido-cholanoic acid) on diet-induced fatty liver in rats, hamsters, and mice. The fatty liver score (on a scale of 0-4 by light microscopy) was 4.0 in control hamsters and 0.3 in the FABAC-fed hamsters (P < .001). In mice it was 1.5 and 0.4, respectively (P < .01). The lipid/protein ratio in the liver was 1.3 ± 0.44 (mg lipid/mg protein) in control rats and 0.66 ± 0.04 in the FABAC group (P = .001) after 14 days. In hamsters it was 1.41 ± 0.27 and 1.11 ± 0.20, respectively (P = .03), after 21 days. In Imperial Charles River (ICR) mice the ratio was 0.34 ± 0.10 and 0.17 ± 0.07 (P = .03), respectively, after 24 days. Liver fat concentration, measured as mg lipid/g liver tissue, decreased similarly by FABAC feeding. The decrease in liver fat affected mainly the triglyceride levels. FABAC-fed animals gained weight similarly to the controls. Triglyceride absorption was unaffected by FABAC supplementation. In conclusion, oral FABAC therapy prevents/reduces the development of fatty liver in animals consuming a HFD. [source] Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinomaHEPATOLOGY, Issue 1 2003Makoto Chuma Hepatocellular carcinoma (HCC) associated with chronic liver disease evolves from precancerous lesions and early HCC to a progressed form. Nodule-in-nodule,type HCC (progressed HCC within early HCC) represents the transition from early to progressed HCC and, therefore, is useful in molecular genetic analysis of HCC progression during multistage carcinogenesis. We compared expression profiles among 7 early components and 7 progressed components of nodule-in-nodule,type HCCs and their corresponding noncancerous liver tissues with oligonucleotide array. Of the approximately 12,600 genes that were analyzed, a set of 95 genes provided a molecular signature that distinguished between early HCC components and their noncancerous liver tissues, and a set of 92 genes distinguished between progressed and early HCC components. Of these genes, the most abundantly up-regulated gene in early HCC components (P < .001) was heat-shock protein 70 (HSP70). Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed this finding. Further immunohistochemical examination of HSP70 revealed its significant overexpression in early HCC compared with precancerous lesions (P < .001) and in progressed HCC compared with early HCC (P < .001). In conclusion, molecular signatures were clearly different in noncancerous liver tissue as compared with the early and progressed components of nodule-in-nodule,type HCC. Moreover, HSP70 could be a sensitive marker for the differential diagnosis of early HCC from precancerous lesion or noncancerous liver, a difficult distinction for pathologists due to very well differentiated histology with little atypia in early HCC. [source] Defective regulation of cholangiocyte Cl,/HCO,3 and Na+/H+ exchanger activities in primary biliary cirrhosisHEPATOLOGY, Issue 6 2002Saida Melero Primary biliary cirrhosis (PBC) is a disorder of unknown origin with autoimmune features. Recently, impaired biliary secretion of bicarbonate has been shown in patients with PBC. Here we have investigated whether bile duct epithelial cells isolated from PBC patients exhibit defects in transepithelial bicarbonate transport by analyzing the activities of 2 ion exchangers, Cl,/HCO,3 anion exchanger 2 (AE2) and Na+/H+ exchanger (NHE) in isolated cholangiocytes. AE2 and NHE activities were studied in basal conditions and after stimulation with cyclic adenosine monophosphate (cAMP) and extracellular adenosine triphosphate (ATP), respectively. Cholangiocytes were grown from needle liver biopsies from 12 PBC patients, 8 normal controls, and 9 patients with other liver diseases. Also, intrahepatic cholangiocytes were cultured after immunomagnetic isolation from normal liver tissue (n = 6), and from recipients undergoing liver transplantation for end-stage PBC (n = 9) and other forms of liver disease (n = 8). In needle-biopsy cholangiocytes, basal AE2 activity was significantly decreased in PBC as compared with normal livers and disease controls. In addition, we observed that though cAMP increased AE2 activity in cholangiocytes from both normal and non-PBC livers, this effect was absent in PBC cholangiocytes. Similarly, though in cholangiocytes from normal and disease control livers extracellular ATP induced a marked enhancement of NHE activity, cholangiocytes from PBC patients failed to respond to purinergic stimulation. In conclusion, our findings provide functional evidence that PBC cholangiocytes exhibit a widespread failure in the regulation of carriers involved in transepithelial H+/HCO,3 transport, thus, providing a molecular basis for the impaired bicarbonate secretion in this cholestatic syndrome. [source] Expression of cystic fibrosis transmembrane conductance regulator in liver tissue from patients with cystic fibrosisHEPATOLOGY, Issue 2 2000Nils Kinnman M.D. The authors examined the expression of cystic fibrosis transmembrane conductance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression of CFTR, intercellular adhesion molecule-1 (ICAM-1) and liver cell-type markers in liver cryosections in 11 patients with CF-associated liver disease, and non-CF controls with (n = 17) and without (n = 3) liver disease. In CF patients prominent inflammatory infiltrates were not found, yet hepatic stellate cells were identified within fibrotic areas around bile ducts. Proliferating bile ducts displayed ICAM-1 immunoreactivity in 3 cases, but bile ducts were otherwise negative. In 2 patients homozygous for R764X and for 1112delT no CFTR immunoreactivity was detected. Bile-duct epithelial cells in patients carrying the ,F508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR, as determined with confocal laser scanning microscopy, in contrast to the distinct CFTR expression at the luminal surface seen in controls. No clear relationship between CFTR expression and fibrosis or inflammation was evidenced in CF patients. In conclusion, these findings are consistent with an impairment of ,F508 CFTR processing in intrahepatic biliary epithelium. ICAM-1 expression on bile-duct epithelial cells and inflammatory infiltrates were rare findings in CF liver tissue, indicating that immunological mechanisms are unlikely to be involved in initiation of CF-associated liver disease. [source] | ||||||||||||||||||||||||||||||||||||||||