Contribution of Toll‐like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration

Ekihiro Seki, Hiroko Tsutsui, Yuji Iimuro, Tetsuji Naka, Gakuhei Son, Shizuo Akira, Tadamitsu Kishimoto, Kenji Nakanishi, Jiro Fujimoto – 22 February 2005 – Toll‐like receptors (TLRs) act as innate immune signal sensors and play central roles in host defense. Myeloid differentiation factor (MyD) 88 is a common adaptor molecule required for signaling mediated by TLRs. When the receptors are activated, cells bearing TLRs produce various proinflammatory cytokines in a MyD88‐dependent manner.

The human liver clears both asymmetric and symmetric dimethylarginine

Michiel P.C. Siroen, Joost R. M. van der Sijp, Tom Teerlink, Cors van Schaik, Robert J. Nijveldt, Paul A. M. van Leeuwen – 22 February 2005 – Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) inhibit production of nitric oxide. The concentration of both dimethylarginines is regulated by urinary excretion, although ADMA, but not SDMA, is also subject to degradation by dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver but also present in the kidney. The exact roles of the human liver and kidney in the metabolism of dimethylarginines are currently unknown.

Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests

Armando Tripodi, Francesco Salerno, Veena Chantarangkul, Marigrazia Clerici, Massimo Cazzaniga, Massimo Primignani, Pier Mannuccio Mannucci – 22 February 2005 – The role played by coagulation defects in the occurrence of bleeding in cirrhosis is still unclear. This is partly due to the lack of tests that truly reflect the balance of procoagulant and anticoagulant factors in vivo.

Pantoprazole reduces the size of postbanding ulcers after variceal band ligation: A randomized, controlled trial

Nicholas J. Shaheen, Eugene Stuart, Sarah M. Schmitz, Kate L. Mitchell, Michael W. Fried, Steven Zacks, Mark W. Russo, Joseph Galanko, Roshan Shrestha – 22 February 2005 – Elective esophageal variceal ligation (EVL) is performed to decrease the risk of variceal hemorrhage. Side effects of EVL include hemorrhage, chest pain, dysphagia, and odynophagia. Because gastric acid may exacerbate postbanding ulcers and delay healing, proton pump inhibition may decrease side effects associated with EVL.

Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: A multicenter trial

Joaquin de la Peña, Enric Brullet, Eloy Sanchez‐Hernández, Monserrat Rivero, Mercedes Vergara, Jose Luis Martin‐Lorente, Covadonga Garcia Suárez – 22 February 2005 – β‐Blockers and endoscopic variceal ligation (EVL) have proven to be valuable methods in the prevention of variceal rebleeding. The aim of this study was to compare the efficacy of EVL combined with nadolol versus EVL alone as secondary prophylaxis for variceal bleeding. Patients admitted for acute variceal bleeding were treated during emergency endoscopy with EVL or sclerotherapy and received somatostatin for 5 days.

Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts

Kumiko Isse, Kenichi Harada, Yoh Zen, Takashi Kamihira, Shinji Shimoda, Mine Harada, Yasuni Nakanuma – 22 February 2005 – Fractalkine is a chemokine with both chemoattractant and cell‐adhesive functions, and in the intestine it is involved with its receptor CX3CR1 in the chemoattraction and recruitment of intraepithelial lymphocytes. We examined the pathophysiological roles of fractalkine and CX3CR1 in normal and diseased bile ducts.

No relevant effect of ursodeoxycholic acid on cytochrome P450 3A metabolism in primary biliary cirrhosis

Karin Dilger, Annette Denk, Malte H. J. Heeg, Ulrich Beuers – 22 February 2005 – Induction of cytochrome P450 3A (CYP3A) has been suggested as a mechanism of action of ursodeoxycholic acid (UDCA) in cholestasis. CYP3A is of key importance in human drug metabolism, being involved in presystemic extraction of more than 50% of all drugs currently available and of various endogenous compounds. Therefore, we compared the induction potential of UDCA with that of the prototypical inducer rifampicin in a human model study with the CYP3A substrates budesonide and cortisol.

TNFα‐mediated extracellular matrix remodeling is required for multiple division cycles in rat hepatocytes

Anne‐Laure Sérandour, Pascal Loyer, Delphine Garnier, Brice Courselaud, Nathalie Théret, Denise Glaise, Christiane Guguen‐Guillouzo, Anne Corlu – 22 February 2005 – During liver regeneration, hepatocytes proliferate under the control of both proinflammatory cytokines such as tumor necrosis factor α (TNFα) and growth factors, in parallel to extracellular matrix remodeling. This study investigated mechanisms by which mitogen and extracellular matrix signals are linked for inducing proliferation of differentiated hepatocytes.

Plasmacytoid dendritic cells in acute and chronic hepatitis C virus infection

Axel Ulsenheimer, J. Tilman Gerlach, Maria‐Christina Jung, Norbert Gruener, Martin Wächtler, Markus Backmund, Teresa Santantonio, Winfried Schraut, Malte H. J. Heeg, Carl A. Schirren, Reinhart Zachoval, Gerd R. Pape, Helmut M. Diepolder – 22 February 2005 – Chronic evolution of acute hepatitis C (aHC) occurs in more than 80% of patients but can frequently be prevented by early treatment with interferon (IFN)‐α. Plasmacytoid dendritic cells (pDCs) are the major endogenous IFN‐α producers, but their role in aHC is unknown.

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