Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

R. tomentosus is a vegetal species closely related to the culinary rosemary (R. officinalis), a plant reported to contain antihepatotoxic agents. A dried ethanol extract of the aerial parts of Rosmarinus tomentosus (Lamiaceae) and its major fraction separated by column chromatography (fraction F19) were evaluated for antihepatotoxic activity in rats with acute liver damage induced by a single oral dose of thioacetamide. Silymarin was used as a reference antihepatotoxic substance. Pre-treatment with R. tomentosus ethanol extract, fraction F19 or silymarin significantly reduced the impact of thioacetamide toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma-glutamyl transpeptidase activities compared with thioacetamide-treated animals (group T). Pre-treatment with R. tomentosus ethanol extract significantly reduced the impact of thioacetamide damage on alkaline phosphatase and gamma-glutamyl transpeptidase activities compared with group T. Silymarin administration significantly reduced alkaline phosphatase and gamma-glutamyl transpeptidase activities compared with group T. Fraction F19 administration reduced only alkaline phosphatase activity compared with group T. According to these data, R. tomentosus extract shows promising antihepatotoxic activity, suggesting the need to isolate the chemical principles responsible for this activity and to study this activity in a model of thioacetamide-induced cirrhosis.
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PMID:Antihepatotoxic activity of Rosmarinus tomentosus in a model of acute hepatic damage induced by thioacetamide. 1105 42

Possible molecular mechanisms underlying changes in catalytical properties of alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH) were studied at toxic hepatitis. The development of toxic hepatitis is accompanied by significant changes in the activity of ADH and LDH assayed in subcellular fractions and kinetic characteristics of these enzymes. This can result in an increase cellular level of acetylaldehyde and lactate which promotes the development of liver cirrhosis.
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PMID:[Molecular mechanisms of metabolic adaptation in pathological changed liver during toxic hepatitis ]. 1155 17

Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid in patients with decompensated cirrhosis. The modifier 'spontaneous' distinguishes this from surgical peritonitis. The infecting organisms are usually enteric gram-negatives which have translocated from the bowel. Symptoms of infection occur in most patients with SBP, including fever, abdominal pain, mental status changes, and ileus. A high index of suspicion should exist for SBP in patients with cirrhosis and ascites. Diagnostic abdominal paracentesis can be undertaken with minimal risk and should be performed in all patients admitted to the hospital, during times of worsening clinical appearance, or when gastrointestinal bleeding occurs. The ascitic fluid polymorphonuclear cell count is the most sensitive test in evaluating for infection. Cultures of the ascitic fluid are helpful in identifying the organism and are best performed by bedside injection of blood culture bottles. Ascites total protein, lactate dehydrogenase, and glucose levels can assist in distinguishing SBP from secondary peritonitis. Empirical therapy is recommended after paracentesis if suspicion for infection exists. Cefotaxime is the best-studied antibiotic for this purpose and has excellent penetration into ascites with no nephrotoxicity. Prophylaxis should be limited to high-risk settings. Mortality rates in SBP have declined dramatically, largely due to earlier detection and improved therapy.
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PMID:Spontaneous bacterial peritonitis. 1592 Mar 24

We report here on a case of non-Hodgkin's lymphoma in which liver involvement was the predominant clinical manifestation. A healthy 44-year-old man presented with upper abdominal pain, hepatosplenomegaly, thrombocytopenia, elevated AST, ALT and bilirubin, and marked elevation of lactate dehydrogenase and alkaline phosphatase. The abdominal CT scan showed only diffuse hepatosplenomegaly and uneven contrast enhancement of the spleen without any definite mass of the liver and spleen. US-guided aspiration biopsy of liver and the histologic examination confirmed a diagnosis of non-Hodgkin's lymphoma, the diffuse large B cell type. Bone marrow biopsy showed the infiltration of malignant lymphoma cells. PET-CT showed an increased FDG uptake of the liver, spleen and long bones. The patient was treated with combination regimen of cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy. Even in the absence of a mass lesion or lymphadenopathy, primary hepatic or hepatosplenic lymphoma should be considered in differential diagnosis of hepatitis or liver cirrhosis, especially for patients with diffuse hepatosplenomegaly and markedly elevated LDH.
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PMID:[A case of primary hepatic lymphoma mimicking hepatitis]. 1617 55

Macrophage activating syndrome (MAS) is a rare hematological disorder associated with uncontrolled systemic T-cell activation. Persistent fever, fatigue and hepatosplenomegaly are frequent clinical manifestations, whereas hyperferritinemia, elevated serum lactate dehydrogenase levels and cytopenia are key criteria for the diagnosis of MAS. The nature of liver pathology in MAS has been partially elucidated but destructive biliary lesions have been rarely described. This report illustrates four cases of MAS developing marked cholestasis, leading to one case of biliary cirrhosis necessitating liver transplantation. Histologically, liver involvement was characterized in all cases by acute lobular hepatitis, marked hepatocyte apoptosis and small bile duct injury similar to the vanishing bile duct syndrome. Immuno-histological studies showed that the inflammatory changes and bile duct lesions were dominated by the presence of activated macrophages and T-cells, in particular CD8+ lymphocytes, and in part NK-cells. These findings suggest that in MAS, various T-cell triggers such as infection, autoimmune disease and malignancy might result in the release of cytokines, which in turn activate macrophages to trigger a systemic acute phase response and local tissue damage. This communication suggests that a macrophage, T- and NK-cell network is operational in the pathogenesis of the cholangiocyte, hepatocyte and sinus endothelial cell damage in MAS.
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PMID:Macrophage activating syndrome is associated with lobular hepatitis and severe bile duct injury with cholestasis. 1661 13

Thrombotic microangiopathy (TMA) after liver transplantation is thought to be a rare event. We report a case of TMA after living donor liver transplantation for hepatitis C virus-related cirrhosis. The patient was initially placed on a tacrolimus-based immunosuppressive regimen, and received combined ribavirin and interferon treatment as pre-emptive therapy for hepatitis C virus. His post-transplantation course was complicated by cytomegalovirus (CMV) antigenemia, and intra-abdominal hemorrhage after percutaneous liver biopsy, necessitating laparotomy. On postoperative day (POD) 53, we noted a marked thrombocytopenia with a sudden rise in lactate dehydrogenase. Blood smear indicated prominent fractionated erythrocytes. Treatment included immediate conversion from tacrolimus to cyclosporine (CsA) and successive plasma exchange (PE), despite which the TMA progressed. CsA was discontinued 32 days after initiating the PE, and the TMA progression seemed to cease. However, the patient's condition deteriorated and he died of multiple organ failure on POD 119. We report this case to stress that careful management of calcineurin inhibitor administration is critical in TMA.
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PMID:Late mortality from thrombotic microangiopathy after liver transplantation: report of a case. 1738 72

1. Liver fibrosis is the compensatory state of cirrhosis. In the long asymptomatic period, it is imperative to select a proper dosing regimen for drugs that are applicable to hepatic fibrosis. Otherwise, progressive deterioration to uncompensated cirrhosis may occur. The present study explored the characteristics of drug metabolism in fibrotic liver. 2. A rat precision-cut fibrotic liver slice (PCFLS) technique was established and the metabolism of verapamil was studied employing this technique. A rat hepatic fibrosis model was successfully induced integrating complex factors that included a high-fat diet, alcohol and CCl4. The PCFLS were incubated under different conditions and lactate dehydrogenase leakage, glutathione S-transferase activity and 3[4,5-dimethythiazole-2-yl]-2,5-diphenyltetrazolium bromide reduction were used as indices to assess PCFLS viability. Activities of phase I and phase II metabolizing enzymes were monitored following treatment with cytochrome P450 (CYP) inducers. Normal and fibrotic liver slices were incubated individually with 10 micromol/L verapamil. The concentration of verapamil in the medium was determined by high-performance liquid chromatography and intrinsic clearance (Cl(int)) was calculated on the basis of the concentration-time curve. 3. The results showed that the PCFLS viability remained steady throughout the 6 h of culture when the thickness of slices was 300 microm and pH of the medium was 7.0; CYP inducers (phenobarbital and ethanol) enhanced CYP2E1, CYP3A1/2 and uridine diphosphate-glucuronate transferase (UDPGT) activities, respectively, in a time-dependent manner. The Cl(int) (microL/min per mg) values differed significantly between normal (9.7 +/- 1.8) and fibrotic (5.6 +/- 1.4) liver slices (P < 0.01). 4. These results suggested that the PCFLS could remain viable for 2-6 h under appropriate conditions. The stability and inducibility of drug-metabolizing enzymes of PCFLS were also demonstrated. Furthermore, the metabolic rate of verapamil in PCFLS was decreased. These findings add further support to the use of PCFLS as a tool to study drug metabolism and to guide clinical medication.
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PMID:Establishment of rat precision-cut fibrotic liver slice technique and its application in verapamil metabolism. 1743 8

Previous experiments showed that treatment of mice and rats with thioacetamide (TAA) induced liver cell damage, fibrosis and/or cirrhosis, associated with increased oxidative stress and activation of hepatic stellate cells. Some experiments suggest that CYP2E1 may be involved in the metabolic activation of TAA. However, there is no direct evidence on the role of CYP2E1 in TAA-mediated hepatotoxicity. To clarify this, TAA-induced hepatotoxicity was investigated using Cyp2e1-null mice. Male wild-type and Cyp2e1-null mice were treated with TAA (200 mg/kg of body weight, single, i.p.) at 6 weeks of age, and hepatotoxicity examined 24 and 48 h after TAA treatment. Relative liver weights of Cyp2e1-null mice were significantly different at 24 h compared to wild-type mice (p<0.01). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in Cyp2e1-null mice were significantly different at both time points compared to wild-type mice (p<0.01). Histopathological examination showed Cyp2e1-null mice represented no hepatototoxic lesions, in clear contrast to severe centriobular necrosis, inflammation and hemorrhage at both time points in wild-type mice. Marked lipid peroxidation was also only limited to wild-type mice (p<0.01). Similarly, TNF-alpha, IL-6 and glutathione peroxidase mRNA expression in Cyp2e1-null mice did not significantly differ from the control levels, contrasting with the marked alteration in wild-type mice (p<0.01). Western blot analysis further revealed no increase in iNOS expression in Cyp2e1-null mice. These results reveal that CYP2E1 mediates TAA-induced hepatotoxicity in wild-type mice as a result of increased oxidative stress.
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PMID:Role of CYP2E1 in thioacetamide-induced mouse hepatotoxicity. 1837 80

The aim of this study was to elucidate the antioxidant properties of fucoidan extracts (FE) against CCl(4)-induced oxidative stress by monitoring the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Female, Sparague-Dowley rats were administered with FE (100 mg/kg daily) for 14 days and CCl(4) on the 15'th day, 12 h before they were sacrificed. The levels of GOT, GPT, ALP and LDH in serum of rats, as well as the levels of MDA, SOD, CAT and GPx in total liver homogenate were analyzed. CCl(4)-treatment was found to increase the levels of GOT, GPT, ALP, LDH and MDA, as well as decrease levels of SOD, CAT and GPx significantly. The pre-treatment of rats with FE, however, suppressed the increment of levels of GOT, GPT, ALP, LDH and MDA, as well as recovered the levels of SOD, CAT and GPx in CCl(4)-treated rats. Moreover there was a significant decrease in incidences of necrosis and cirrhosis in the liver tissue of FE-treated rats. These results implied that FE possessed antioxidant properties against CCl(4)-induced oxidative stress.
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PMID:The effects of fucoidan extracts on CCl(4)-induced liver injury. 1848 Oct 19

Hepatocellular carcinoma (HCC) is a major cause of death in Asian countries. The false-negative rate with serum alpha-fetaprotein level alone can reach 40% for early stage HCC patients. Due to the lack of sensitive and specific tumor markers for early diagnosis, it is impossible for HCC patients to receive effective therapy. However, tumor antigens can be recognized by immune cells and be rejected in immune responses. In order to identify antigens which may be used as new markers and immunotherapy targets for HCC, a cDNA expression library derived from an HCC sample was constructed, which was screened with mixed autologous and allogenic serum of HCC patients. Seventeen different HCC antigens were obtained, which are classified as tumor-associated antigens. A panel of allogenic sera from patients with chronic hepatitis, liver cirrhosis, HCC and other tumor entities and sera from health volunteers, was used for frequency analysis of antibody responses. Four of 17 antigens, including eukaryotic translation initiation factor 3, subunit I, lactate dehydrogenase 1, A chain, replication factor C2, 40 kDa and mitochondrial carrier triple repeat 1, reacted predominantly with sera from patients with HCC (31.8, 45.5, 27.3 and 50.0% respectively). Patients (81.8%) with HCC had the antibody against at least one of these four antigens, which indicates that disease-specific humoral response against these antigens was induced in HCC patients and the corresponding antibodies may be used as tumor markers for HCC.
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PMID:Identification of tumor-associated antigens in human hepatocellular carcinoma by autoantibodies. 1881 43


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