Matrix metalloproteinase‐2 activation in human hepatic fibrosis regulation by cell‐matrix interactions

Anne‐Marie Préaux, Ariane Mallat, Jeanne Tran Van Nhieu, Marie‐Pia d'Ortho, Rosalind M. Hembry, Philippe Mavier – 30 December 2003 – Matrix metalloproteinase‐2 (MMP‐2) is involved in extracellular matrix remodeling. It is secreted as a proenzyme and activated by membrane type‐MMPs (MT‐MMP), such as MT1‐MMP. In liver fibrosis, MMP‐2 is highly expressed in myofibroblasts and may have a profibrogenic role. The mechanisms of its activation in the liver are still unclear.

Monocyte chemoattractant protein‐1 enhances expression of intercellular adhesion molecule‐1 following ischemia‐reperfusion of the liver in rats

Yasuo Yamaguchi, Fujio Matsumura, Motohiro Takeya, Osamu Ichiguchi, Jun‐Ichi Kuratsu, Tadashi Horiuchi, Eiji Akizuki, Teishi Matsuda, Kazutoshi Okabe, Hajime Ohshiro, Jian Liang, Katsutaka Mori, Shinwa Yamada, Kiyoshi Takahashi, Michio Ogawa – 30 December 2003 – Intercellular adhesion molecule‐1 (ICAM‐1) is important in neutrophil‐dependent injury. We investigated the effects of monocyte chemoattractant protein‐1 (MCP‐1) produced by Kupffer cells on ICAM‐1 expression after ischemia‐reperfusion in rat liver by occluding the portal vein for 30 minutes.

Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents

Jian Wu, Pei Liu, Jian‐Liang Zhu, Sivaramaiah Maddukuri, Mark A. Zern – 30 December 2003 – To improve liposome‐directed therapy of liver disease and gene delivery, it would be beneficial to selectively target hepatocytes. For this purpose, conventional liposomes (CL) were labeled with asialofetuin (AF), an asialoglycoprotein. The biodistribution of AF‐labeled liposomes (AF‐L) in mice and their incorporation into rat hepatocytes, and their potential use in acute liver injury, were investigated.

Hemodynamic effects of the somatostatin analog lanreotide in humans: Placebo‐controlled, cross‐over dose‐ranging echo‐doppler study

Christian Mottet, Cornel C. Sieber, André Nauer, Jürgen Drewe, Ronald Fried, Finn Larsen, Christoph Beglinger – 30 December 2003 – Because of their vasoactive effects, somatostatin and its analogs are increasingly used in the management of complications of chronic liver diseases such as variceal bleeding. Postprandial hyperemia augments splanchnic blood flow, subsequently increasing portal pressure. The aim of this study was to explore effects of the somatostatin analog, lanreotide, on food‐stimulated hemodynamic parameters in healthy human subjects.

The mouse equivalent of the human p53ser249 mutation p53ser246 enhances aflatoxin hepatocarcinogenesis in hepatitis B surface antigen transgenic and p53 heterozygous null mice

Nader Ghebranious, Stewart Sell – 30 December 2003 – The relative contribution to development of hepatocellular carcinoma of the mouse equivalent to the human p53ser249 mutation, found in human hepatocellular carcinoma associated with aflatoxin (AFB1) exposure, is compared with other major risk factors in a transgenic mouse model. Transgenic p53ser246 mice, expressing the mutant protein gene under the control of a truncated albumin promoter, were bred to mice lacking p53 (p53−/−) and to transgenic mice expressing hepatitis B surface antigen (HBsAg).

Quantification of the initial decline of serum hepatitis c virus RNA and response to interferon alfa

Stefan Zeuzem, Jung‐Hun Lee, Alexa Franke, Brigitte Rüster, Otto Prümmer, Günter Herrmann, W. Kurt Roth – 30 December 2003 – Although several virus‐ and host‐related predictive factors for the response to interferon alfa (IFN‐α) have been defined in patients with chronic hepatitis C, no pretreatment parameter can definitely predict the response to antiviral treatment. Assessment of the initial response by quantification of serum hepatitis C virus RNA before and 4 weeks after initiation of therapy may be a clinically applicable and reliable parameter to predict long‐term response.

Inhibition of establishment and growth of mouse liver metastases after treatment with interferon gamma and β‐1,3‐D‐glucan

Baldur Sveinbjørnsson, Christian Rushfeldt, Rolf Seljelid, Bård Smedsrød – 30 December 2003 – The purpose of this study was to investigate the combined antitumor effect of aminated β‐1,3‐d‐glucan (AG) and interferon‐gamma (IFN‐γ) in an experimental liver metastasis model. Liver metastases were established by inoculation of C‐26 colon carcinoma cells into the superior mesenteric vein of syngeneic mice. Treatment of mice started 24 hours after inoculation of tumor cells by daily intravenous injections of either AG, IFN‐γ, or a combination of both for a duration of 6 days.

Neurovisual impairment: A frequent complication of alpha‐interferon treatment in chronic viral hepatitis

Emanuel K. Manesis, Michael Moschos, Dimitrios Brouzas, John Kotsiras, Constantine Petrou, George Theodosiadis, Stephanos Hadziyannis – 30 December 2003 – Following our earlier observation of clinically evident optic tract neuropathy in patients receiving low‐dose interferon (IFN) therapy, we prospectively evaluated 53 consecutive patients treated for chronic hepatitis B or C with a median dose of 3 MU of IFN‐a2b thrice weekly.

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