Mutations in the hepatitis C virus polymerase that increase RNA binding can confer resistance to cyclosporine A

Zhe Liu, John M. Robida, Sreedhar Chinnaswamy, Guanghui Yi, Jason M. Robotham, Heather B. Nelson, Andre Irsigler, C. Cheng Kao, Hengli Tang – 23 June 2009 – Hepatitis C virus (HCV) infection leads to acute and chronic liver diseases, and new classes of anti‐HCV therapeutics are needed. Cyclosporine A (CsA) inhibits HCV replication and CsA derivatives that lack the immunosuppressive function are currently in clinical trials as candidate anti‐HCV drugs.

CCR2 promotes hepatic fibrosis in mice

Ekihiro Seki, Samuele de Minicis, Sayaka Inokuchi, Kojiro Taura, Katsumi Miyai, Nico van Rooijen, Robert F. Schwabe, David A. Brenner – 23 June 2009 – Chemokines and chemokine receptors contribute to the migration of hepatic stellate cells (HSCs) and Kupffer cells, two key cell types in fibrogenesis. Here, we investigate the role of CCR2, the receptor for monocyte chemoattractant protein (MCP)‐1, MCP‐2, and MCP‐3, in hepatic fibrosis. Hepatic CCR2, MCP‐1, MCP‐2, and MCP‐3 messenger RNA expression was increased after bile duct ligation (BDL).

Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis

Stephen H. Caldwell, Luiz Antonio R. de Freitas, Sang H. Park, Maria Lucia V. Moreno, Jan A. Redick, Christine A. Davis, Barbee J. Sisson, James T. Patrie, Helma Cotrim, Curtis K. Argo, Abdullah Al‐Osaimi – 28 May 2009 – Mitochondrial dysfunction is an important element in the pathogenesis of nonalcoholic steatohepatitis (NASH). Intramitochondrial crystals (IMCs) are a well‐documented morphological abnormality seen on transmission electron microscopy in this disease.

Side chain structure determines unique physiologic and therapeutic properties of norursodeoxycholic acid in Mdr2−/− mice

Emina Halilbasic, Romina Fiorotto, Peter Fickert, Hanns‐Ulrich Marschall, Tarek Moustafa, Carlo Spirli, Andrea Fuchsbichler, Judith Gumhold, Dagmar Silbert, Kurt Zatloukal, Cord Langner, Uday Maitra, Helmut Denk, Alan F. Hofmann, Mario Strazzabosco, Michael Trauner – 28 May 2009 – 24‐norursodeoxycholic acid (norUDCA), a side chain–modified ursodeoxycholic acid derivative, has dramatic therapeutic effects in experimental cholestasis and may be a promising agent for the treatment of cholestatic liver diseases.

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