Entry and integration of transplanted hepatocytes in rat liver plates occur by disruption of hepatic sinusoidal endothelium

Sanjeev Gupta, Pankaj Rajvanshi, Rana Sokhi, Sanjeev Slehria, Ana Yam, Andrew Kerr, Phyllis M. Novikoff – 30 December 2003 – To establish the process by which transplanted cells integrate into the liver parenchyma, we used dipeptidyl peptidase IV‐deficient F344 rats as hosts. On intrasplenic injection, transplanted hepatocytes immediately entered liver sinusoids, along with attenuation of portal vein radicles on angiography. However, a large fraction of transplanted cells (>70%) was rapidly cleared from portal spaces by phagocyte/macrophage responses.

Monocyte chemotactic protein‐1 as a chemoattractant for human hepatic stellate cells

Fabio Marra, Roberto G. Romanelli, Carlo Giannini, Paola Failli, Sabrina Pastacaldi, Maria Cristina Arrighi, Massimo Pinzani, Giacomo Laffi, Paolo Montalto, Paolo Gentilini – 30 December 2003 – Following liver injury, hepatic stellate cells (HSC) undergo proliferation and migrate into damaged areas in response to chemotactic factors. HSC have been shown to regulate leukocyte trafficking by secreting monocyte chemotactic protein‐1 (MCP‐1), a chemokine that recruits monocytes and lymphocytes. In this study, we explored whether MCP‐1 exerts biological actions on HSC.

The protective role of adenosine in inducing nitric oxide synthesis in rat liver ischemia preconditioning is mediated by activation of adenosine A2 receptors

Carmen Peralta, Georgina Hotter, Daniel Closa, Neus Prats, Carme Xaus, Emilio Gelpí, Joan Roselló‐Catafau – 30 December 2003 – This study aims to determine if the protective role of adenosine in liver ischemic preconditioning is mediated by the activation of adenosine receptors and to ascertain which of these receptors is implicated in the process. Administration of adenosine A1 and A2 receptor antagonists to preconditioned animals indicates that hepatic preconditioning is mediated by the activation of adenosine A2 receptors.

Hematopoietic support and cytokine expression of murine‐stable hepatocyte cell lines (MMH)

Alessandro Aiuti, Carla Cicchini, Silvia Bernardini, Giorgio Fedele, Laura Amicone, Antonio Fantoni, Marco Tripodi – 30 December 2003 – It was recently reported that transgenic expression in the liver of truncated human Met renders hepatocytes constitutively resistant to apoptosis and reproducibly permits their immortalization. The derived stable cell lines (MMH from Met murine hepatocyte) are highly differentiated and nontransformed. In this report, the capacity of MMHs to support in vitro hematopoiesis is characterized.

Activation of rat hepatic stellate cells in culture is associated with increased sensitivity to endothelin 1

Roland M. Reinehr, Ralf Kubitz, Thorsten Peters‐Regehr, Johannes G. Bode, Dieter Häussinger – 30 December 2003 – The effect of endothelin (ET) 1 on intracellular Ca2+ transients in cultured rat hepatic stellate cells (HSCs) during transformation was studied by use of single‐cell fluorescence. Regardless of the duration of HSC culture, ET‐1 caused a BQ‐123–sensitive but IRL‐1038–insensitive elevation of [Ca2+]i, indicating the involvement of ETA but not ETB receptors.

Enhanced release of nitric oxide in response to changes in flow and shear stress in the superior mesenteric arteries of portal hypertensive rats

Naoki Hori, Reiner Wiest, Roberto J. Groszmann – 30 December 2003 – Increased nitric oxide (NO) release has been implicated in the pathogenesis of the hyperdynamic circulation in portal hypertension. NOS 3 (eNOS) causes NO release from the endothelium in response to physical stimuli, such as increased blood flow and shear stress. We evaluated the functional activity of the endothelium in the superior mesenteric arterial bed of portal hypertensive rats through direct measurement of NO metabolites (NOx) during changes in flow and shear stress.

Blunted thrombopoietin response to interferon alfa–induced thrombocytopenia during treatment for hepatitis C

Markus Peck‐Radosavljevic, Martina Wichlas, Johann Pidlich, Paul Sims, Gloria Meng, Johannes Zacherl, Shaily Garg, Christian Datz, Alfred Gangl, Peter Ferenci – 30 December 2003 – Thrombocytopenia is common in advanced‐stage liver disease and is partly caused by inadequate thrombopoietin (TPO) production in the failing liver. Treatment of chronic hepatitis C with interferon alfa (IFN‐α) often induces thrombocytopenia, sometimes even leading to discontinuation of treatment.

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