Acute Disease ; Antigens, CD ; blood ; Antigens, Differentiation, Myelomonocytic ; blood ; Hepatitis, Viral, Human ; classification ; pathology ; therapy ; Humans ; Liver Failure, Acute ; etiology ; pathology ; therapy ; Liver Transplantation ; Liver, Artificial ; Prognosis ; Receptors, Cell Surface ; blood ; Troponin I ; blood

Acute-On-Chronic Liver Failure ; blood ; pathology ; Case-Control Studies ; Cytochrome Reductases ; metabolism ; Humans ; Prospective Studies ; alpha-Fetoproteins ; metabolism

Alanine Transaminase ; blood ; Animals ; Bilirubin ; blood ; Disease Models, Animal ; Endotoxemia ; etiology ; Endotoxins ; blood ; Gastrointestinal Hormones ; blood ; Gastrointestinal Motility ; physiology ; Intestine, Small ; physiopathology ; Liver ; pathology ; Liver Failure, Acute ; blood ; etiology ; physiopathology ; Liver Function Tests ; Rats ; Thioacetamide ; administration & dosage

OBJECTIVETo study the role of tumor necrosis factor-alpha (TNFalpha) on enterocyte apoptosis in the experimental model of fulminant hepatic failure (FHF).

METHODSLiver damage was induced by lipopolysaccharide (LPS)/TNFalpha in D-galactosamine (GalN) sensitized BALB/c mice. Serum TNFalpha levels were determined by enzyme-linked immunosorbent assays (ELISA). The intestinal tissues were studied micro- and ultra-microscopically at 2 h, 6 h, 9 h, 12 h and 24 h time points in mice with fulminant hepatic failure. Enterocyte apoptosis was determined by TUNEL method. The TNFR I expression in the intestinal tissue was tested by immunohistochemistry.

RESULTS(1) Gut mucosa was morphologically normal at every time point in all groups, but typical apoptotic cells could be seen in the experimental groups under the electron microscope. Apoptosis rate of gut mucosal epithelial cells was significantly increased at 6 h (large intestine: 6.47e(-3)+/-2.91e(-4); small intestine: 6.64e(-3)+/-3.78e(-4)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 h (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)), and peaked at 12 h in mice with FHF. (2) TNFalpha induced apoptosis of enterocytes in mice with FHF. Anti-TNFalpha inhibited this effect. (3) The integrated OD (IOD) levels of TNFalpha receptor I protein expressed differently in the intestine of mice with GalN/LPS and GalN/ TNFalpha-induced FHF at 9 h after GalN/LPS and GalN/ TNFalpha administration, in comparison with those of the control groups. IOD level of TNFRI changed significantly at 6 h (large intestine: 2.82e(+4)+/-4.60e(+3); small intestine: 1.14e(+4)+/-2.13e(+3)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)) hours after GalN/LPS and GalN/ TNFa administration. The expression of TNFR1 protein was significantly higher at 9 and 12 h after GalN/LPS and GalN/TNFa administration than other time points. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis.

CONCLUSIONTNFa can induce enterocyte apoptosis in mice with FHF. Anti- TNFalpha IgG can inhibit this role. Excessive TNFRI expression of enterocyte in fulminant hepatic failure can be induced by TNFa, which suggests that TNFalpha can induce apoptosis of enterocyte by up-regulation of TNFRI protein expression.

Animals ; Apoptosis ; physiology ; Enterocytes ; pathology ; Galactosamine ; Lipopolysaccharides ; Liver Failure, Acute ; chemically induced ; pathology ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; blood

Animals ; Biotransformation ; Cell Line, Tumor ; Cell Proliferation ; Culture Media ; Diazepam ; pharmacokinetics ; Fibroblasts ; metabolism ; pathology ; Hepatitis, Chronic ; blood ; complications ; Humans ; Liver Failure, Acute ; blood ; etiology ; Liver Neoplasms ; metabolism ; pathology ; Plasma

OBJECTIVE: To study the effect of alprostadil lipid microballoons (lipo PGE1) on the function and morphous of livers from brain-dead rats. METHODS: Twenty-four SD rats were randomly assigned into 4 groups: a control group(Group C),a brain-dead group (Group B) and 2 lipo PGE1 protection groups (Group L1 and Group L2). Brain-dead models were established in Group B,L1 and L2.There was no inflation of Fogarty balloon in Group C, while other operations were the same as Group B. Lipo PGE1 [20 ng/(kg.min) and 40 ng/(kg.min)] was injected via the femoral vein in Group L1 and Group L2 immediately after the establishment of the brain-dead model. The serum levels of alanine aminotransferase (ALT), aspartate amino transferase (AST), endothelin (ET)-1, and tumor necrosis factor (TNF)-α were detected by radioimmunological analyzer. Liver tissues were observed by HE staining 6 h after the brain death. RESULTS: At the time of brain death, the level of ALT, AST, ET-1, and TNF-α in Group B, L1 and L2 was significantly different compared with that in Group C. That in Group L1 and L2 was significantly lower than in Group B(P<0.05). There was no significant difference between Group L1 and L2(P>0.05). CONCLUSION Brain death can cause damage to the liver of rats. Lipo PGE1 can relieve the injury of brain death donors.The protective mechanism of Lipo PGE1 is to decrease the release of serum inflammatory mediators.
Alprostadil ; pharmacology ; Animals ; Brain Death ; blood ; pathology ; physiopathology ; Endothelin-1 ; blood ; Female ; Liver Failure, Acute ; blood ; etiology ; prevention & control ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood

Critical Illness ; DNA, Viral ; blood ; genetics ; Genotype ; Hepatitis B Surface Antigens ; blood ; genetics ; Hepatitis B virus ; classification ; genetics ; physiology ; Hepatitis B, Chronic ; pathology ; virology ; Humans ; Liver Failure, Acute ; pathology ; virology ; Mutation ; Promoter Regions, Genetic ; genetics ; Virus Replication

AIMTo study the therapeutic effects of N,N'-diacetyl-L-cystine (DiNAC) on immunological liver failure.

METHODSSerum ALT, AST and T cell subsets in peripheral blood of the experimental animals during the trial period were analyzed by an automatic serum analyzer and a flow cytometer, respectively. The sectioned liver specimens were examined under a light microscope. And 24 h after the injection of Gal/LPS, the survival rate of rats was calculated.

RESULTSDiNAC (50, 200, 800 mg x kg(-1), i.p.) suppressed the elevation of serum levels of ALT and AST, markedly enhanced proliferation and differentiation of T cell subsets (CD4+, CD8+ and Th1, Th2), and improved all the histopathological features. In mice of fulminant hepatic failure (FHF), the survival time significantly prolonged and the survival rate increased 24 h after i.p. DiNAC. These effects were obviously dose-dependent.

CONCLUSIONDiNAC on mice with FHF has an inhibitory action which is related to immune mechanism.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; CD4 Antigens ; metabolism ; CD8 Antigens ; metabolism ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cystine ; analogs & derivatives ; pharmacology ; Liver ; pathology ; Liver Failure, Acute ; blood ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes ; pathology

OBJECTIVETo investigate the expression and role of augmenter of liver regeneration (ALR) in hepatic failure.

METHODSALR polyclonal antibody was prepared and purified. Serum ALR in patients with hepatic failure, chronic hepatitis B and healthy persons were quantified by ELISA, ALR mRNA in hepatic tissues were quantified by real-time PCR.

RESULTSDifferent serum ALR levels foreshowed different outcomes for hepatic failure patients: The liver function was restored in 6 patients with higher ALR level [(1613.5+/-369.6) pmol/ml], and the liver function was deteriorated in 12 patients with lower ALR level [(462.3+/-235.8) pmol/ml]. ALR level in patients with chronic hepatitis B [(969.2+/-332.5) pmol/ml] was similar to that in healthy persons [(806.9+/-240.8) pmol/ml]. ALR mRNA level in hepatic failure patients receiving OLT (103.45 copies/microl) was lower than that in chronic hepatitis B patients (104.37 copies/microl) and healthy persons (104.31 copies/microl), ALR mRNA level in chronic hepatitis B and healthy persons was similar.

CONCLUSIONThese findings suggest serum ALR level reflected ALR mRNA level in liver and is helpful in estimating the survival time of patients with hepatic failure.

Animals ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Expression ; Hepatitis B, Chronic ; blood ; metabolism ; pathology ; Hepatocytes ; metabolism ; Humans ; Liver ; metabolism ; pathology ; Liver Failure, Acute ; blood ; metabolism ; pathology ; Liver Regeneration ; Mice ; Mice, Inbred BALB C ; Polymerase Chain Reaction ; methods ; Prognosis ; Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Recombinant Proteins ; genetics ; metabolism

The objective of this study was to develop an experimental animal model of fulminant hepatic failure to test the efficacy of the bioartificial liver system. The portal vein and the hepatic artery were clamped intermittently and then the hepatic artery was ligated (ligation group, n=5). Pigs whose hepatic arteries were not ligated after clamping were assigned to the non-ligation group (n=5). The biochemical changes in blood, histologic alterations of the liver and neurologic examination for pigs were checked up. All animals died within 17 hr in the ligation group. On the other hand, all animals survived more than 7 days in the non-ligation group. In the ligation group, the levels of ammonia, lactic acid and creatinine showed a progressively increasing pattern. Prothrombin time was also prolonged gradually. Cytoplasmic condensation and nuclear pyknosis of hepatocytes were detected histologically at autopsy. Neurologic findings such as decreased pain sensation, tachypnea and no light reflex of pupils were observed. The findings shown in the ligation group are similar to the clinical features of fulminant hepatic failure in human and this animal model is reproducible. Therefore, this can be a suitable animal model to evaluate the efficacy of the bioartificial liver system for treating fulminant hepatic failure.
Acidosis/etiology/prevention & control ; Ammonia/blood ; Animals ; Aspartate Aminotransferases/blood ; Bilirubin/blood ; Blood Glucose/metabolism ; Blood Urea Nitrogen ; Comparative Study ; Creatinine/blood ; *Disease Models, Animal ; Female ; Hepatic Artery/surgery ; Lactic Acid/blood ; Ligation/adverse effects ; Liver Failure, Acute/blood/*pathology ; Portal Vein/surgery ; Potassium/blood ; Prothrombin Time ; Research Support, Non-U.S. Gov't ; Sodium Bicarbonate/pharmacology ; Swine