Olprinone attenuates excessive shear stress through up‐regulation of endothelial nitric oxide synthase in a rat excessive hepatectomy model

Kenya Yamanaka, Etsuro Hatano, Masato Narita, Koji Kitamura, Atsuko Yanagida, Hiroyuki Asechi, Hiromitsu Nagata, Kojiro Taura, Takashi Nitta, Shinji Uemoto – 21 September 2010 – After extended hepatectomy, excessive shear stress in the remnant liver causes postoperative liver failure. Olprinone (OLP), a selective phosphodiesterase inhibitor, has been reported to improve microcirculation and attenuate inflammation. The aim of this study was to investigate the effects of OLP on shear stress in rats with an excessive hepatectomy (EHx) model.

Human T cell microparticles circulate in blood of hepatitis patients and induce fibrolytic activation of hepatic stellate cells

Miroslaw Kornek, Yury Popov, Towia A. Libermann, Nezam H. Afdhal, Detlef Schuppan – 20 September 2010 – Microparticles (MPs) are small cell membrane vesicles that are released from cells during apoptosis or activation. Although circulating platelet MPs have been studied in some detail, the existence and functional role of T cell MPs remain elusive. We show that blood from patients with active hepatitis C (alanine aminotransferase [ALT] level >100 IU/mL) contains elevated numbers of T cell MPs compared with patients with mild hepatitis C (ALT <40 IU/mL) and healthy controls.

Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis

Wing‐Kin Syn, Steve S. Choi, Evaggelia Liaskou, Gamze F. Karaca, Kolade M. Agboola, Ye Htun Oo, Zhiyong Mi, Thiago A. Pereira, Marzena Zdanowicz, Padmini Malladi, Yuping Chen, Cynthia Moylan, Youngmi Jung, Syamal D. Bhattacharya, Vanessa Teaberry, Alessia Omenetti, Manal F. Abdelmalek, Cynthia D. Guy, David H. Adams, Paul C. Kuo, Gregory A. Michelotti, Peter F. Whitington, Anna Mae Diehl – 20 September 2010 – Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Recently, we showed that NASH‐related cirrhosis is associated with Hedgehog (Hh) pathway activation.

Lupeol targets liver tumor‐initiating cells through phosphatase and tensin homolog modulation

Terence Kin Wah Lee, Antonia Castilho, Vincent Chi Ho Cheung, Kwan Ho Tang, Stephanie Ma, Irene Oi Lin Ng – 20 September 2010 – Liver tumor‐initiating cells (T‐ICs) are capable of self‐renewal and tumor initiation and are more chemoresistant to chemotherapeutic drugs. The current therapeutic strategies for targeting stem cell self‐renewal pathways therefore represent rational approaches for cancer prevention and treatment.

Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis

Herbert Tilg, Alexander R. Moschen – 20 September 2010 – Whereas in most cases a fatty liver remains free of inflammation, 10%‐20% of patients who have fatty liver develop inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Inflammation may precede steatosis in certain instances. Therefore, NASH could reflect a disease where inflammation is followed by steatosis. In contrast, NASH subsequent to simple steatosis may be the consequence of a failure of antilipotoxic protection.

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Marco Antonio Montes‐Cano, José Raúl García‐Lozano, Cristina Abad‐Molina, Manuel Romero‐Gómez, Natalia Barroso, José Aguilar‐Reina, Antonio Núñez‐Roldán, María Francisca González‐Escribano – 17 September 2010

Ribavirin potentiates interferon action by augmenting interferon‐stimulated gene induction in hepatitis C virus cell culture models

Emmanuel Thomas, Jordan J. Feld, Qisheng Li, Zongyi Hu, Michael W. Fried, T. Jake Liang – 14 September 2010 – The combination of pegylated interferon (PEG‐IFN) and ribavirin is the standard treatment for chronic hepatitis C. Our recent clinical study suggests that ribavirin augments the induction of interferon‐stimulated genes (ISGs) in patients treated for hepatitis C virus (HCV) infection. In order to further characterize the mechanisms of action of ribavirin, we examined the effect of ribavirin treatment on ISG induction in cell culture.

Organic anion–transporting polypeptide 1b2 (Oatp1b2) is important for the hepatic uptake of unconjugated bile acids: Studies in Oatp1b2‐null mice

Iván L. Csanaky, Hong Lu, Youcai Zhang, Kenichiro Ogura, Supratim Choudhuri, Curtis D. Klaassen – 14 September 2010 – The organic anion–transporting polypeptide 1b family (Oatp1b2 in rodents and OATP1B1/1B3 in humans) is liver‐specific and transports various chemicals into the liver. However, the role of the Oatp1b family in the hepatic uptake of bile acids (BAs) into the liver is unknown. Therefore, in Oatp1b2‐null mice, the concentrations of BAs in plasma, liver, and bile were compared with wild‐type (WT) mice.

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