Steven M. Kerfoot, Charlotte D'Mello, Henry Nguyen, Maureen N. Ajuebor, Paul Kubes, Tai Le, Mark G. Swain – 22 December 2005 – Signaling occurs between the liver and brain in cholestatic liver disease, giving rise to sickness behaviors such as fatigue. However, the signaling pathways involved are poorly defined. Circulating inflammatory mediator levels are increased in cholestasis, leading to speculation that they may be capable of activating circulating immune cells that subsequently could gain access to the brain.

Pengfei Gong, Arthur I. Cederbaum – 22 December 2005 – Induction of CYP2E1 by ethanol is one pathway through which ethanol generates oxidative stress. Nrf2 is a transcription factor that regulates important antioxidant and phase II detoxification genes. Nrf2 induction by CYP2E1 and its importance in the adaptive response to increased oxidative stress caused by CYP2E1 was studied. Increases in Nrf2 protein and mRNA were observed in livers or hepatocytes of chronic alcohol‐fed mice or rats and of pyrazole‐treated rats or mice, conditions known to elevate CYP2E1.

Xiaokun Ding, Neeraj K. Saxena, Songbai Lin, Narita Gupta, Frank A. Anania – 22 December 2005 – Nonalcoholic fatty liver disease (NAFLD) represents a burgeoning problem in hepatology, and is associated with insulin resistance. Exendin‐4 is a peptide agonist of the glucagon‐like peptide (GLP) receptor that promotes insulin secretion. The aim of this study was to determine whether administration of Exendin‐4 would reverse hepatic steatosis in ob/ob mice. Ob/ob mice, or their lean littermates, were treated with Exendin‐4 [10 μg/kg or 20 μg/kg] for 60 days.

Dennis M. Jensen – 22 December 2005

Calogero Cammà, Savino Bruno, Vito Di Marco, Danilo Di Bona, Mariagrazia Rumi, Maria Vinci, Chiara Rebucci, Agostino Cividini, Giuseppe Pizzolanti, Ernesto Minola, Mario U. Mondelli, Massimo Colombo, Giovanbattista Pinzello, Antonio Craxfì – 22 December 2005 – Conflicting data exist regarding the relationship between hepatitis C virus genotype 1 and hepatic steatosis as well as the latter's role in the progression of fibrosis and treatment response.

Juan Turnes, Manuel Hernández‐Guerra, Juan G. Abraldes, Pau Bellot, Rafael Oliva, Juan Carlos García‐Pagán, Jaime Bosch – 22 December 2005 – The beta‐2‐adrenergic receptor (β2‐‐AR) has several single‐nucleotide polymorphisms. These influence the functional response to adrenergic stimulation; genotypes homozygous for Gly16‐Glu27 or Gly16‐Gln27 alleles (Gly16‐Glu/Gln27 haplotypes) are associated with enhanced response, whereas genotypes homozygous for Arg16‐Gln27 alleles (Arg16‐Gln27) show a decreased response.

Ying Huang, Xinyi Cynthia Chen, Madhavi Konduri, Nadejda Fomina, Jin Lu, Ling Jin, Alexander Kolykhalov, Seng‐Lai Tan – 22 December 2005 – Interferon‐gamma (IFN‐γ) exerts potent antiviral activity in the hepatitis C virus (HCV) replicon systems. However, the mechanisms underlying the direct antiviral effect have not been determined. We found that the type II transcriptional response to IFN‐γ could be suppressed by inhibition of MEK1/2 kinase activity by MEK1/2 inhibitor U0126 in the hepatoma cell line Huh‐7.

Walid S. Kamoun, Amel Karaa, Nicole Kresge, Sandra M. Merkel, Katarzyna Korneszczuk, Mark G. Clemens – 22 December 2005 – During endotoxemia, liver microcirculation disruption is characterized by a hypersensitivity to the constrictor effects of endothelin 1 (ET‐1). The shift of ET‐1–mediated effects toward vasoconstriction may result from depressed ET‐1–mediated vasodilation through decreased ET‐1–induced nitric oxide (NO) production.

Susanne Keiding, Michael Sørensen, Dirk Bender, Ole Lajord Munk, Peter Ott, Hendrik Vilstrup – 22 December 2005 – Animal studies and results from 13N‐ammonia positron emission tomography (PET) in patients with cirrhosis and minimal hepatic encephalopathy suggest that a disturbed brain ammonia metabolism plays a pivotal role in the pathogenesis of hepatic encephalopathy (HE).

Eva Martínez‐Bauer, Javier Crespo, Manuel Romero‐Gómez, Ricardo Moreno‐Otero, Ricard Solá, Nancy Tesei, Fernando Pons, Xavier Forns, José M. Sánchez‐Tapias – 22 December 2005 – Early prediction of response to therapy in genotype 1 chronic hepatitis C is difficult. Two predictive models, a pretreatment scoring model (PreT‐SM) and a fourth week of therapy scoring model (4w‐SM) were constructed in a cohort of 104 patients from a single center (estimation cohort) and validated in a cohort of 141 patients from four independent centers (validation cohort).