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Liver Pathology (liver + pathology)
Selected AbstractsGastrointestinal and Liver PathologyHISTOPATHOLOGY, Issue 1 2006A K Dube No abstract is available for this article. [source] Decreased Proteasome Activity Is Associated With Increased Severity of Liver Pathology and Oxidative Stress in Experimental Alcoholic Liver DiseaseALCOHOLISM, Issue 8 2004Terrence M. Donohue Jr Background: Because of its role in degrading the bulk of intracellular proteins and eliminating damaged proteins, the proteasome is important in maintaining cell viability. Previously, we showed a 35,40% decrease in proteasome peptidase activity when ethanol was administered to rats by intragastric infusion. We hypothesized that this reduction was caused by ethanol-elicited oxidative stress, the degree of which varies depending on the method of ethanol administration. This study examined the relationship of proteasome activity and content with ethanol-induced oxidative stress and the degree of liver injury. Methods: Rats were given ethanol or isocaloric dextrose-containing liquid diets by intragastric infusion for 1 month. The diets contained medium-chain triglycerides (MCT), palm oil (PO), corn oil (CO), or fish oil (FO) as the principal source of fat. Results: Rats given ethanol and MCT exhibited no significant liver pathology, whereas cumulative pathology scores in ethanol-fed rats given PO, CO, or FO were 2.5, 5.4 and 7.0, respectively, indicating that ethanol and FO caused the greatest liver damage. The severity of liver pathology in the last three groups of animals correlated with levels of lipid peroxides and serum 8-isoprostanes. Alpha smooth muscle actin, an indicator of stellate cell activation, was increased relative to controls in the livers of all ethanol-fed rats except FO-fed animals, in which both control and ethanol-fed rats had similar levels of this protein. In livers of CO and FO ethanol-fed rats, proteasome chymotrypsin-like activity was decreased by 55,60%, but there was no quantitative alteration in 20S proteasome subunit content. In contrast, ethanol affected neither proteasome activity nor its content in MCT- and PO-treated animals. Conclusions: Our findings indicate that the severity of liver injury and ethanol-induced oxidative stress is associated with a reduction in proteasome catalysis. [source] Liver pathology in compound heterozygous patients for hemochromatosis mutationsLIVER INTERNATIONAL, Issue 4 2002Maximilian Schöniger-Hekele Abstract: Background: While hepatic pathology of homozygous carriers of the C282Y mutation of the HFE haemochromatosis gene is well defined, the impact of the C282Y/H63D compound heterozygous carrier state is unknown. Aims: To evaluate the range of hepatic pathology in C282Y/H63D compound heterozygous patients. Patients: 25 C282Y/H63D compound heterozygous patients with and without known underlying liver disease underwent liver biopsies for evaluation or abnormal liver tests. Eleven cadaveric liver donors with HFE wild type served as controls. Methods: Mutations in the HFE gene were detected by polyacrylamide gel electrophoresis (PAGE) separation of digested polymerase chain reaction (PCR)-amplificates. The extent of light microscopic changes of liver architecture were studied on haematoxylin, eosin (H. E.) stains. In addition, the extent and the distribution of iron deposition was graded on Prussian blue-stained sections and hepatic iron was quantified by atom absorption spectroscopy. Serum ferritin concentration and the transferrin saturation index were measured using routine laboratory methods. Results: Patients without underlying liver disease (n = 15): Hepatic inflammation was seen in only 8% but fibrosis was found in 36% of compound heterozygous patients. Eighty six percent of those patients had stainable iron predominantly found in Rappaport's zone 1 and 2, but all had a liver iron-index < 1.9. Transferrin saturation was found elevated in 36% of compound heterozygous patients. Patients with liver fibrosis showed significantly higher ferritin levels than patients without liver fibrosis (1110 ng/mL versus 307 ng/mL, p < 0.05). Patients with underlying disease (n = 10): In compound heterozygous patients, 77% had hepatic inflammation and 88% fibrosis. Stainable iron (44%) was less frequently found than in patients without underlying liver disease. Hepatic iron-index in patients with underlying liver disease was always below 1.17; transferrin saturation was elevated in only 22% of the compound heterozygous patients. Histologic hepatic iron-index was significantly lower in patients with underlying disease (median 0.047) as compared to patients without underlying liver disease (median 0.274, P < 0.05). Conclusions: The underlying liver disease determines the extent of hepatic pathology seen in livers of compound heterozygous patients. However, considerable histologic fibrosis can also be found in compound heterozygous patients without underlying liver disease. [source] Further studies on the hepatoprotective effects of Anoectochilus formosanus,PHYTOTHERAPY RESEARCH, Issue 3 2008Hsun-Lang Fang Abstract The purpose of this study was to investigate the hepatoprotective effects of Anoectochilus formosanus effective fraction (AFEF) on chronic liver damage induced by carbon tetrachloride (CCl4) in mice. CCl4 (5%; 0.1 mL/10 g body weight) was given twice a week for 9 weeks, and mice received AFEF throughout the whole experimental period. Plasma GPT, hepatic levels of hydroxyproline and malondialdehyde were significantly lower in mice treated with AFEF compared with those treated with CCl4 only. Liver pathology in the AFEF-treated mice was also improved. RT-PCR analysis showed that AFEF treatment increased the expression of methionine adenosyltransferase 1A and decreased the expression of collagen(,1)(I) and transforming growth factor-,1. These results clearly demonstrated that AFEF reduced the hepatic damage induced by CCl4 in mice. Copyright © 2007 John Wiley & Sons, Ltd. [source] Alteration in regulation of inflammatory response to influenza a virus and endotoxin in suckling rat pups: a potential relationship to sudden infant death syndromeFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2004Jane Blood-Siegfried Abstract Data increasingly implicate a possible role of immune and inflammatory responses to infection in sudden infant death syndrome (SIDS). We have previously described a dual challenge model that results in pathology, organ damage, vascular collapse and unexplained death similar to that seen in SIDS. In this study, we examined changes in inflammatory cytokine mRNA in the lung and liver and regulation of pathways associated with nitric oxide production. Our data suggest that priming of the immune system by mild viral infection disturbs normal inflammatory response to endotoxin. This results in an increased nitric oxide synthase production, most likely the cause of liver pathology and clotting abnormalities. [source] Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver diseaseHEPATOLOGY, Issue 4 2004Feng Hong Fatty liver, formerly associated predominantly with excessive alcohol intake, is now also recognized as a complication of obesity and an important precursor state to more severe forms of liver pathology including ischemia/reperfusion injury. No standard protocol for treating fatty liver exists at this time. We therefore examined the effects of 10 days of interleukin 6 (IL-6) injection in 3 murine models of fatty liver: leptin deficient ob/ob mice, ethanol-fed mice, and mice fed a high-fat diet. In all 3 models, IL-6 injection decreased steatosis and normalized serum aminotransferase. The beneficial effects of IL-6 treatment in vivo resulted in part from an increase in mitochondrial , oxidation of fatty acid and an increase in hepatic export of triglyceride and cholesterol. However, administration of IL-6 to isolated cultured steatotic hepatocytes failed to decrease lipid contents, suggesting that the beneficial effects of IL-6 in vivo do not result from its effects on hepatocytes alone. IL-6 treatment increased hepatic peroxisome proliferator-activated receptor (PPAR) , and decreased liver and serum tumor necrosis factor (TNF) ,. Finally, 10 days of treatment with IL-6 prevented the susceptibility of fatty livers to warm ischemia/reperfusion injury. In conclusion, long-term IL-6 administration ameliorates fatty livers and protects against warm ischemia/reperfusion fatty liver injury, suggesting the therapeutic potential of IL-6 in treating human fatty liver disease. Supplementary material for this article can be found on the Hepatology website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2004;40:933,941.) [source] Novel approaches to assessing renal function in cirrhotic liver diseaseHEPATOLOGY RESEARCH, Issue 9 2007Andrew J. Portal Renal dysfunction is common in patients with end-stage liver disease. Etiological factors include conditions as diverse as acute tubular necrosis, immunoglobulin A nephropathy and hepatorenal syndrome. Current standard tests of renal function, such as measurement of serum urea and creatinine levels, are inaccurate as the synthesis of these markers is affected by the native liver pathology. This article reviews novel markers of renal function and their potential use in patients with liver disease. [source] Altered aquaporin 9 expression and localization in human hepatocellular carcinomaHPB, Issue 1 2009Srikanth Padma Abstract Background:, In addition to the biochemical components secreted in bile, aquaporin (AQP) water channels exist in hepatocyte membranes to form conduits for water movement between the sinusoid and the bile canaliculus. The aim of the current study was to analyse AQP 9 expression and localization in human hepatocellular carcinoma (HCC) and non-tumourigenic liver (NTL) tissue from patients undergoing hepatic resection. Methods:, Archived tissue from 17 patients was sectioned and analysis performed using an antibody raised against AQP 9. Slides were blind-scored to determine AQP 9 distribution within HCC and NTL tissue. Results:, Aquaporin 9 was predominantly expressed in the membranes of hepatocytes and demonstrated zonal distribution relative to hepatic sinusoid structure in normal liver. In HCC arising in the absence of cirrhosis AQP 9 remained membrane-localized with zonal distribution in the majority of NTL. By contrast, AQP 9 expression was significantly decreased in the HCC mass vs. pair-matched NTL. In HCC in the presence of cirrhosis, NTL was characterized by extensive AQP 9 staining in the membrane in the absence of zonal distribution and AQP 9 staining in NTL was significantly greater than that observed in the tumour mass. Conclusions:, These data demonstrate that human HCC is characterized by altered AQP 9 expression and AQP 9 localization in the NTL mass is dependent on underlying liver pathology. Given the central role of AQPs in normal liver function and the potential role of AQPs during transformation and progression, these data may prove valuable in future diagnostic and/or therapeutic strategies. [source] Does chloroquine therapy of porphyria cutanea tarda influence liver pathology?INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2009U Wollina MD Background, Porphyria cutanea tarda (PCT) is regularly associated with changes in liver tissue. On the other hand, systematic investigations are lacking on whether there is a correlation between the severity of liver damage and chloroquine treatment. Patients and methods, During a 20-year period, liver biopsies were obtained in 89 patients with PCT confirmed by biochemical analysis of urine and feces and low-dose chloroquine therapy. Seventeen patients with alcohol-induced liver disease were excluded. In 8 of 63 patients, only a single biopsy was available. Classification of liver damage was performed according to the Riedel score. Electron microscopy was available from 24 patients. In a second group of patients, the HFE status was investigated and Berlin blue stains of liver biopsies were performed. Results, There was no correlation between the duration of cutaneous symptoms and liver pathology. After 12 months chloroquine treatment, 45 patients (81%) disclosed an improvement of liver pathology, nine (16%) had no change, and a worsening was observed in one patient (3%). All patients achieved a complete clinical and biochemical remission. In 13 of 16 patients with a relapse, there was again a deterioration of liver damage. Patients with HFE mutations had a significant higher risk (P < 0.05) for hepatic siderosis. Conclusions, The severity of liver damage was not correlated with the disease duration. Chloroquine treatment resulted in PCT remission (clinical and biochemical) and in 81% to an improvement of liver morphology. [source] Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2010Marion Levast Abstract The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real-time PCR techniques are available commercially and can detect more reliably low HBV DNA levels. The aim of this study was to determine the prevalence of occult hepatitis B virus infection using the COBAS Taqman assay (Roche Diagnostics, Meylan, France) in the serum and liver of HBsAg negative patients with chronic hepatitis C and to evaluate its clinical consequences on liver pathology and its impact on the response to treatment with peg-IFN, and Ribavirin. HBV DNA detection was assessed retrospectively on 140 sera and 113 liver biopsies of HCV positive/HBsAg negative patients before treatment. A 4.4% (5/113) prevalence of occult hepatitis B was recorded in liver samples and in none of the sera. Anti-HBc was not detected in one, three of whom were sustained virological responders to treatment, one was relapsed responder and one was non-responder. Furthermore, in this cohort composed of 12% anti-HBs negative/anti-HBc positive and 20% anti-HBs positive/anti-HBc positive patients, anti-HBc was not associated with pre-therapeutic viral load, ALT serum levels, and histological activity or fibrosis. Using a commercial real-time PCR assay, we observed a low prevalence of occult B hepatitis. This, just as anti-HBC status, had no clinical impact in a large cohort of hepatitis C patients. It therefore does not appear useful to screen for occult hepatitis B in these patients with this test before beginning HCV treatment. J. Med. Virol. 82: 000,000, 2010. © 2010 Wiley-Liss, Inc. J. Med. Virol. 82: 747,754, 2010. © 2010 Wiley-Liss, Inc. [source] Diagnosis and management of paediatric hepatitis C virus infectionJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 3 2002AM Kesson Abstract: Hepatitis C virus (HCV) infection in children is uncommon and there are few guidelines indicating optimal management. It is estimated that 125,250 children are infected vertically with HCV in Australia each year and very few of these children are diagnosed and followed medically. Without accurate diagnosis and follow up, these children cannot be offered optimal care, and are at risk of presenting in adult life with significant liver pathology and long-term sequelae. [source] Emerging Role of Epigenetics in the Actions of AlcoholALCOHOLISM, Issue 9 2008Shivendra D. Shukla This review deals with the recent developments on the epigenetic effects of ethanol. A large body of data have come from studies in liver and in neuronal systems and involve post-translational modifications in histones and methylations in DNA. Ethanol causes site selective acetylation, methylation, and phosphorylation in histone. With respect to methylations the methyl group donating system involving S-adenosyl methionine appears to play a central role. There is contrasting effect of acetylation versus methylation on the same site of histone, as it relates to the transcriptional activation. Epigenetic memory also appears to correlate with liver pathology and Mallory body formation. Experimental evidence supports transcriptional regulation of genes in the CNS by DNA methylations. These studies are contributing towards a better understanding of a novel epigenetic regulation of gene expression in the context of alcohol. The critical steps and the enzymes (e.g., histone acetyltransferase, histone deacetylase, DNA methyltransferase) responsible for the epigenetic modifications are prime targets for intense investigation. The emerging data are also beginning to offer novel insight towards defining the molecular actions of ethanol and may contribute to potential therapeutic targets at the nucleosomal level. These epigenetic studies have opened up a new avenue of investigation in the alcohol field. [source] Decreased Proteasome Activity Is Associated With Increased Severity of Liver Pathology and Oxidative Stress in Experimental Alcoholic Liver DiseaseALCOHOLISM, Issue 8 2004Terrence M. Donohue Jr Background: Because of its role in degrading the bulk of intracellular proteins and eliminating damaged proteins, the proteasome is important in maintaining cell viability. Previously, we showed a 35,40% decrease in proteasome peptidase activity when ethanol was administered to rats by intragastric infusion. We hypothesized that this reduction was caused by ethanol-elicited oxidative stress, the degree of which varies depending on the method of ethanol administration. This study examined the relationship of proteasome activity and content with ethanol-induced oxidative stress and the degree of liver injury. Methods: Rats were given ethanol or isocaloric dextrose-containing liquid diets by intragastric infusion for 1 month. The diets contained medium-chain triglycerides (MCT), palm oil (PO), corn oil (CO), or fish oil (FO) as the principal source of fat. Results: Rats given ethanol and MCT exhibited no significant liver pathology, whereas cumulative pathology scores in ethanol-fed rats given PO, CO, or FO were 2.5, 5.4 and 7.0, respectively, indicating that ethanol and FO caused the greatest liver damage. The severity of liver pathology in the last three groups of animals correlated with levels of lipid peroxides and serum 8-isoprostanes. Alpha smooth muscle actin, an indicator of stellate cell activation, was increased relative to controls in the livers of all ethanol-fed rats except FO-fed animals, in which both control and ethanol-fed rats had similar levels of this protein. In livers of CO and FO ethanol-fed rats, proteasome chymotrypsin-like activity was decreased by 55,60%, but there was no quantitative alteration in 20S proteasome subunit content. In contrast, ethanol affected neither proteasome activity nor its content in MCT- and PO-treated animals. Conclusions: Our findings indicate that the severity of liver injury and ethanol-induced oxidative stress is associated with a reduction in proteasome catalysis. [source] Disease Stage Characterization of Hepatorenal Fibrocystic Pathology in the PCK Rat Model of ARPKDTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2010Stephen B. Mason Abstract The rat Pck gene is orthologous to the human PKHD1 gene responsible for autosomal recessive polycystic kidney disease (ARPKD). Both renal and hepatic fibrocystic pathology occur in ARPKD. Affected humans have a variable rate of progression, from morbidly affected infants to those surviving into adulthood. This study evaluated the PCK rat, a model of slowly progressive ARPKD. This model originated in Japan and was rederived to be offered commercially by Charles River Laboratories (Wilmington, MA). Previous studies have described the basic aspects of PCK pathology from privately held colonies. This study provides a comprehensive characterization of rats from those commercially available. Rats were bred, maintained on a 12:12 hr light/dark cycle, fed (7002 Teklad), and water provided ad libitum. Male and female rats were evaluated from 4 through 35 weeks of age with histology and serum chemistry. As the hepatorenal fibrocystic disease progressed beyond 18 weeks, the renal pathology (kidney weight, total cyst volume) and renal dysfunction (BUN and serum creatinine) tended to be more severe in males, whereas liver pathology (liver weight as % of body weight and hepatic fibrocystic volume) tended to be more severe in females. Hyperlipidemia was evident in both genders after 18 weeks. Bile secretion was increased in PCK rats compared with age-matched Sprague Dawley rats. The PCK is an increasingly used orthologous rodent model of human ARPKD. This characterization study of hepatorenal fibrocystic pathology in PCK rats should help researchers select stages of pathology to study and/or monitor disease progression during their longitudinal studies. Anat Rec 293:1279,1288, 2010. © 2010 Wiley-Liss, Inc. [source] Efficacy against Fasciola hepatica and the pharmacokinetics of triclabendazole administered by oral and topical routesAUSTRALIAN VETERINARY JOURNAL, Issue 5 2009PJ Martin Objective To determine the efficacy of triclabendazole (TCBZ) against 28-day-old, early immature liver fluke in cattle and its pharmacokinetics following administration by the oral or topical (pour-on) route. Procedures Cattle (n = 18) were infected with 500 TCBZ-susceptible liver fluke metacercariae and randomly allocated to three groups. At 28 days after infection, the groups were: (1) untreated controls; (2) treated with oral TCBZ at 12 mg/kg in combination with oxfendazole and selenium (TOS); (3) treated with pour-on TCBZ at 30 mg/kg in combination with abamectin (TA). Blood samples were taken immediately prior to treatment and serially after treatment to assess the plasma profile of TCBZ metabolites. Ten weeks after treatment all animals were slaughtered and total liver fluke counts, fluke egg counts and liver pathology were assessed. Results Both the TOS and TA treatments resulted in significant reductions of 28-day-old liver fluke, as assessed by fluke counts and fluke egg counts at slaughter, and the reductions following TOS treatment were significantly greater than those following TA treatment. The blood profile of TCBZ metabolites in TOS-treated animals showed a significantly greater area under the plasma concentration time curve and a higher maximum observed concentration than those treated with TA. There was significantly less liver pathology in TOS-treated animals than in the TA-treated animals. Conclusion TCBZ administered orally at 12 mg/kg resulted in greater efficacy against 28-day-old, early immature liver fluke than was achieved by topical administration at 30 mg/kg. Plasma metabolites of TCBZ were higher and liver pathology was less in TOS-treated animals than in TA-treated animals. [source] | |||||||||||||