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| 1 | Acute-on-Chronic Liver Failure Is a Distinct Syndrome That Develops in Patients With Acute Decompensation of Cirrhosis显示文摘 | Richard Moreau Rajiv Jalan Pere Gines Marco Pavesi Paolo Angeli Juan Cordoba Francois Durand Thierry Gustot Faouzi Saliba Marco Domenicali Alexander Gerbes Julia Wendon Carlo Alessandria Wim Laleman Stefan Zeuzem Jonel Trebicka Mauro Bernardi Vicente Arro | 2013 | Gastroenterology2013，，7： | 12 |
| 2 | Stimulation of p38 MAPK by hormal preconditioning with atrial natriuretic peptide显示文摘AIM:Stress-activated signaling pathways responsible for hepatic ischemia reperfusion injury and their modulation by protective interventions are widely unknown.Preconditioning of rat livers with Atrial Natriuretic Peptide(ANP)attenuates ischemia reperfusion injury(Gerbes et al.Hepatology1998,18:1309-1317),SinANP has recently been shown to be a regulator of the p38MAPKpathway in endothelial cells(Kiemer et al.CircRes2002,90:874-881).aim of this thudy was to investigate activities of MAPK during ischemia and reperfusion and effects of ANP on MAPK.METHODS:Rat livers were perfused with KH-buffer in the presence or absence of ANP for 20min,kept in cold UWsloution for 24h,and reperfused forupto120min,Activities of p38MAPKand JNKwas determined by in vitro phosphorylation assays using MBP and c-jun as substrates.After SDS/PAGE electrophoresis,gels were quantified by phosphorimaging.RESULTS:Activity of p38MAPKin control organs decreased in the course of ischemia and reperfusion by85%,whereas ANPincreased p38 activity by up to 30-fold.JNKactivation of control livers increased in the course of ischemia and reperfusion by up to three-fold.This increase in JNK activrity was slightly elevated in ANP preconditioned organs.CONCLUSION:This work represents a systematic investigation of MAPK activation during liver ischemia and reperfusion.Employing ANP,for the first time a pharmacological approach to modulate these central signal transduction molecules is presented. | Alexandra K. Kiemer Stefanie Kulhanek-Heinze Tobias Gerwig Alexander L. Gerbes Angelika M. Vollmar | 2002 | World Journal of Gastroenterology2002，8，4： | 7 |
| 3 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 4 | PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptide in rat liver transplantation显示文摘AIM:To investigate the in vivo effect of atrial natriureticpeptide(ANP)and its signaling pathway during ortho-topic rat liver transplantation.METHODS:Rats were infused with NaCl,ANP(5 μg/kg),wortmannin(WM,16 μg/kg),or a combination ofboth for 20 min.Livers were stored in UW solution(4°C)for 24 h,transplanted and reperfused.Apoptosis wasexamined by caspase-3 activity and TUNEL staining.Phosphorylation of Akt and Bad was visualized by West-ern blotting and phospho-Akt-localization by confocalmicroscopy.RESULTS:ANP-pretreatment decreased caspase-3activity and TUNEL-positive cells after cold ischemia,indicating antiapoptotic effects of ANP in vivo.The an-tiapoptotic signaling of ANP was most likely caused byphosphorylation of Akt and Bad,since pretreatment withPI 3-kinase inhibitor WM abrogated the ANP-inducedreduction of caspase-3 activity.Interestingly,analysis ofliver tissue by confocal microscopy showed translocationof phosphorylated Akt to the plasma membrane of hepa-tocytes evoked by ANP.CONCLUSION:ANP activates the PI-3-kinase pathwayin the liver in vivo leading to phosphorylation of Bad, an event triggering antiapoptotic signaling cascade inischemic liver. | Uwe Grutzner Melanie Keller Michael Bach Alexandra K Kiemer Herbert Meissner Manfred Bilzer Stefan Zahler Alexander L Gerbes Angelika M Vollmar | 2006 | World Journal of Gastroenterology2006，12，7： | 3 |
| 5 | Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis显示文摘 | V Arroyo P Gines AL Gerbes FJ Dudley P Gentilini G Laffi TB Reynolds H Ring-Larsen J Scholmerich | 1996 | Hepatology1996，，1： | 3 |
| 6 | Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis显示文摘 | V Arroyo P Gines AL Gerbes FJ Dudley P Gentilini G Laffi TB Reynolds H Ring-Larsen J Scholmerich | 1996 | Hepatology1996，，1： | 2 |
| 7 | Definition and diagnostic criteriaof refractory ascites and hepatorenal syndrome in cirrhosis显示文摘 | ARROYO V GINES P GERBES A L | 1996 | Hepatology1996，23，： | 1 |
| 8 | Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis显示文摘 | Arroyo V Gines P Gerbes AL | 1996 | Hepatology1996，23，1： | 1 |
| 9 | Ascitic fluid analysis for the differentation of malignancy-related and nonmalignant ascites 显示文摘 | Gerbes AL Jungst D Xie YN | 1991 | Cancer1991，68，8： | 1 |
| 10 | Evaluation of serum Cystatin C concentration as a marker of renal function in patients with cirrhosis of the liver显示文摘 | Gerbes AL Gulberg V Bilzer M | | 0，，： | 1 |
| 11 | An updated paradigm for scale development incorporating unidimensionality and its assessment 显示文摘 | Gerbing D W Anderson J C | 1988 | Journal of Marketing Research1988，25，2： | 1 |
| 12 | Structural Equation Modelling in Practice:A Review and Recommended Two-step Approach显示文摘 | GERBING D W | 1988 | Psychological Bulletin1988，103，3： | 1 |
| 13 | Structural Equation Modeling in Practice:A Review and Recommended Two - Step Approach 显示文摘 | Anderson James C David W Gerbing | 1988 | Psychology Bulletin1988，103，3： | 1 |
| 14 | Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis显示文摘 | Salerno F Gerbes A Gines P | 2007 | Gut2007，56，9： | 1 |
| 15 | Glutathione protects the rat liver against reperfusion injury after hypothermic preservation显示文摘 | Bilzer M Paumgartner G Gerbes A L | 1999 | Gastroenterol1999，117，： | 1 |
| 16 | Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosls显示文摘 | Arroyo V Gines P Gerbes A | 1996 | Hepatology1996，23，： | 1 |
| 17 | Definition and diagnostic criteria of retractory ascites and hepatorenal syndrome in cirrhosis显示文摘 | Arroyo V Ginès P Gerbes AL | | 0，，01： | 1 |
| 18 | Structural Equation Modeling in Practice:A Review and Recommended Two-step Approach显示文摘 | Anderson J C Gerbing D W | 1988 | Psychological Bulletin1988，103，： | 1 |
| 19 | Structural Equation Modeling in Practice: A Review and Recommended Two-step Approach 显示文摘 | Anderson J C Gerbing D W | 1988 | Psychological Bulletion1988，103，3： | 1 |
| 20 | Transcription of brain natriuretic peptide and atrial natriuretic peptide gene in human tissues显示文摘 | Gerbes AL Dagnino L Nguyen T | 1994 | J Clin Endocrinol Metab1994，78，： | 1 |
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