Effects of F‐180, a new selective vasoconstrictor peptide, compared with terlipressin and vasopressin on systemic and splanchnic hemodynamics in a rat model of portal hypertension

Cristina Bernadich, Juan‐Carlos Bandi, Per Melin, Jaime Bosch – 30 December 2003 – The present study is aimed at characterizing the portal, splanchnic, and systemic circulatory effects of F‐180, a new long‐acting analog of vasopressin (VP) with selective effect on the vascular (V1 ) receptor, both in normal rats and in portal‐hypertensive animals. In preliminary vasopressor tests, F‐180 was 18 times more potent than terlipressin (TP) (164 ± 10 IU × mmol−1 vs. 9.2 ± 1.2 IU × mmol−1) and four times less potent than arginine VP (614 ± 25 IU × mmol−1).

Lack of C/EBPα gene expression results in increased DNA synthesis and an increased frequency of immortalization of freshly isolated mice hepatocytes

Humberto E. Soriano, Dong C. Kang, Milton J. Finegold, M. John Hicks, Nai‐Dy Wang, Wilbur Harrison, Gretchen J. Darlington – 30 December 2003 – The CCAAT/enhancer binding protein α (C/EBPα) binds to specific promoter sequences and directs transcription of many genes expressed in the liver. Overexpression of C/EBPα in established cell lines inhibits cell proliferation. Primary hepatocytes from newborn C/EBPα(−/−) mice and normal littermates were used to determine whether the absence of C/EBPα increased proliferation and/or transformation of these cells in vitro.

The portal lobule in rat liver fibrosis: A re‐evaluation of the liver unit

Ekapot Bhunchet, Kenjiro Wake – 30 December 2003 – We re‐evaluated three schemes of liver organization: the classic lobule, the portal lobule, and Rappaport's liver acinus. The lobular angioarchitecture of normal rat liver and the three‐dimensional structure of pseudolubules found in rat livers with fibrosis induced by swine serum were compared with the classic lobule of the pig. Normal and fibrotic rat livers and pig livers were perfused, injected with either India ink or 0.75% OsO4 through the portal and/or hepatic vein, and immersionfixed.

Kupffer cell depletion partially prevents hepatic heme oxygenase 1 messenger RNA accumulation in systemic inflammation in mice: Role of interleukin 1β

Milena Rizzardini, Massimo Zappone, Pia Villa, Paola Gnocchi, Marina Sironi, Luisa Diomede, Cristina Meazza, Mario Monshouwer, Lavinia Cantoni – 30 December 2003 – The heme oxygenase 1 (HO‐1) gene is rapidly activated in the liver after lipopolysaccharide (LPS) treatment. Ninety minutes after LPS treatment (0.1 mg/kg, intraperitoneally) hepatic HO‐1 messenger RNA (mRNA) of mice was 40 times the control value.

Role of nitric oxide in acetaminophen‐induced hepatotoxicity in the rat

Carol R. Gardner, Diane E. Heck, Chung S. Yang, Paul E. Thomas, Xu‐Jie Zhang, George L. DeGeorge, Jeffrey D. Laskin, Debra L. Laskin – 30 December 2003 – Acetaminophen is a mild analgesic and antipyretic agent known to cause centrilobular hepatic necrosis at toxic doses. Although this may be due to a direct interaction of reactive acetaminophen metabolites with hepatocyte proteins, recent studies have suggested that cytotoxic mediators produced by parenchymal and nonparenchymal cells also contribute to the pathophysiological process.

Intracellular distribution of the Wilson's disease gene product (atpase7b) after in vitro and in vivo exogenous expression in hepatocytes from the LEC rat, an animal model of Wilson's disease

Koji Nagano, Kimitoshi Nakamura, Ken‐Ich Urakami, Kazuhiro Umeyama, Hideki Uchiyama, Kazunori Koiwai, Shinzaburo Hattori, Tetsuro Yamamoto, Ichiro Matsuda, Fumio Endo – 30 December 2003 – In patients with Wilson's disease, both copper incorporation into ceruloplasmin and excretion of this metal into bile are impaired. These conditions are caused by a genetic defect in the Wilson's disease gene (ATP7B).

Hemopexin from four species inhibits the association of heme with cultured hepatoma cells or primary rat hepatocytes exhibiting a small number of species specific hemopexin receptors

Shigeru Taketani, Stephan Immenschuh, Sien Go, Peter R. Sinclair, Richard J. Stockert, H. Heng Liem, Ursula Muller Eberhard – 30 December 2003 – Hemopexin (Hx) binds heme with a very high affinity (Kd<0.1 pmol/L). It has been implicated as a major vehicle for the transport of heme into liver cells, involving a receptor‐mediated recycling mechanism.

Use and outcome of liver transplantation in acetaminophen‐induced acute liver failure

William Bernal, Julia Wendon, Mohamed Rela, Nigel Heaton, Roger Williams – 30 December 2003 – Once defined clinical criteria are fulfilled in acetaminophen‐induced hepatotoxicity, prognosis without orthotopic liver transplantation (OLT) may be very poor. In the present study, we examined the application and outcome of OLT in 548 patients admitted to a single center between 1990 and 1996. Four hundred twenty‐four (77%) of the patients studied did not fulfill transplantation criteria, and 396 of these (93%) survived.

Combination therapy with thymosin α1 and interferon for the treatment of chronic hepatitis C infection: A randomized, placebo‐controlled double‐blind trial

Kenneth E. Sherman, Maria Sjogren, Robin L. Creager, Melissa A. Damiano, Stephen Freeman, Scot Lewey, Dirk Davis, Spencer Root, Frederick L. Weber, Kamal G. Ishak, Zachary D. Goodman – 30 December 2003 – Hepatitis C is a major cause of liver disease leading to cirrhosis. Although interferon (IFN) is the only approved therapy, treatment is characterized by low response rates and dose‐limiting side effects.

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