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Massimo Primignani, Giovanni Barosi, Gaetano Bergamaschi, Umberto Gianelli, Federica Fabris, Raffaella Reati, Alessandra Dell'Era, Paolo Bucciarelli, Pier Mannuccio Mannucci – 26 February 2007

Protection against Fas‐induced liver apoptosis in transgenic mice expressing cyclooxygenase 2 in hepatocytes

Marta Casado, Belén Mollá, Rosa Roy, Amalia Fernández‐Martínez, Carme Cucarella, Rafael Mayoral, Lisardo Boscá, Paloma Martín‐Sanz – 26 February 2007 – Cyclooxygenase‐2 (COX‐2) is upregulated in many cancers, and the prostanoids synthesized increase proliferation, improve angiogenesis, and inhibit apoptosis in several tissues. To explore the function of COX‐2 in liver, transgenic (Tg) mice were generated containing a fusion gene (LIVhCOX‐2) consisting of human COX‐2 cDNA under the control of the human ApoE promoter.

The model for end‐stage liver disease (MELD)

Patrick S. Kamath, W. Ray Kim – 26 February 2007 – The Model for End‐stage Liver Disease (MELD) was initially created to predict survival in patients with complications of portal hypertension undergoing elective placement of transjugular intrahepatic portosystemic shunts. The MELD which uses only objective variables was validated subsequently as an accurate predictor of survival among different populations of patients with advanced liver disease. The major use of the MELD score has been in allocation of organs for liver transplantation.

The G‐protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells

Verena Keitel, Roland Reinehr, Petros Gatsios, Claudia Rupprecht, Boris Görg, Oliver Selbach, Dieter Häussinger, Ralf Kubitz – 26 February 2007 – Sinusoidal endothelial cells (SEC) constitute a permeable barrier between hepatocytes and blood. SEC are exposed to high concentrations of bile salts from the enterohepatic circulation. Whether SEC are responsive to bile salts is unknown. TGR5, a G‐protein–coupled bile acid receptor, which triggers cAMP formation, has been discovered recently in macrophages.

Novel aspects of PPARα‐mediated regulation of lipid and xenobiotic metabolism revealed through a nutrigenomic study

Pascal G. P. Martin, Hervé Guillou, Frédéric Lasserre, Sébastien Déjean, Annaig Lan, Jean‐Marc Pascussi, Magali SanCristobal, Philippe Legrand, Philippe Besse, Thierry Pineau – 26 February 2007 – Peroxisome proliferator‐activated receptor‐α (PPARα) is a major transcriptional regulator of lipid metabolism. It is activated by diverse chemicals such as fatty acids (FAs) and regulates the expression of numerous genes in organs displaying high FA catabolic rates, including the liver.

Prevention of hepatocyte allograft rejection in rats by transferring adenoviral early region 3 genes into donor cells

Elena V. Mashalova, Chandan Guha, Namita Roy‐Chowdhury, Laibin Liu, Ira J. Fox, Jayanta Roy‐Chowdhury, Marshall S. Horwitz – 26 February 2007 – Hepatocyte transplantation is being evaluated as an alternative to liver transplantation for metabolic support during liver failure and for definitive treatment of inherited liver diseases. However, as with liver transplantation, transplantation of allogeneic hepatocytes requires prolonged immunosuppression with its associated untoward effects.

Impairment of hepatic Stat‐3 activation and reduction of PPARα activity in fructose‐fed rats

Núria Roglans, Laia Vilà, Mireia Farré, Marta Alegret, Rosa María Sánchez, Manuel Vázquez‐Carrera, Juan Carlos Laguna – 26 February 2007 – Fructose makes up a significant proportion of energy intake in westernized diets; its increased consumption has paralleled the growing prevalence of obesity and metabolic syndrome over the past two decades. In the current study, we demonstrate that fructose administration (10% wt/vol) in the drinking water of rats reduces the trans‐activating and trans‐repressing activity of the hepatic peroxisome proliferator‐activated receptor α (PPARα).

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