Tumor necrosis factor α regulates nitric oxide synthase expression in portal hypertensive gastric mucosa of rats

Masayuki Ohta, Andrzej S. Tarnawski, Rabiha Itani, Rama Pai, Morimasa Tomikawa, Keizo Sugimachi, I. James Sarfeh – 30 December 2003 – Anti–tumor necrosis factor α (TNF‐α) treatment decreases nitric oxide (NO) synthesis and ameliorates the hyperdynamic circulation in portal hypertensive rats. We have recently demonstrated that nitric oxide synthase isoform 3 (NOS3) is overexpressed in portal hypertensive gastric mucosa and that resultant NO overproduction probably is responsible for the increased susceptibility of the mucosa to damage.

Role of cyclic guanosine monophosphate and K+ channels as mediators of the mesenteric vascular hyporesponsiveness in portal hypertensive rats

Noemí M. Atucha, M. Clara Ortíz, Lourdes A. Fortepiani, Francisco M. Ruiz, Concepción Martínez, Joaquín García‐Estañ – 30 December 2003 – The mechanisms mediating the hyporesponsiveness to vasoconstrictors in portal hypertension are not completely established. In the present study, we evaluated the role of cyclic guanosine monophosphate (cGMP) and potassium channels as contributors to the pressor hyporesponsiveness to methoxamine (MTX) of the mesenteric vascular bed of portal vein‐ligated (PVL) hypertensive rats.

Expression of the thrombin receptor in human liver: Up‐regulation during acute and chronic injury

Fabio Marra, Raffaella DeFranco, Cecilia Grappone, Stefano Milani, Massimo Pinzani, Giulia Pellegrini, Giacomo Laffi, Paolo Gentilini – 30 December 2003 – Thrombin is generated during tissue damage in several organs, including the liver, and participates in the process of tissue repair through proteolytic activation of a specific thrombin receptor(TR).The aim of this study was to investigate TR expression in human liver by immunohistochemistry and in situ hybridization. In normal liver, immunostaining for TR was present in the endothelial lining of the hepatic sinusoids.

Transferrin and transferrin receptor gene expression and iron uptake in hepatocellular carcinoma in the rat

Rosa Maria Pascale, Maria Rosaria De Miglio, Maria Rosaria Muroni, Maria Maddalena Simile, Lucia Daino, Maria Antonietta Seddaiu, Stefano Pusceddu, Leonardo Gaspa, Diego Calvisi, Giacomo Manenti, Francesco Feo – 30 December 2003 – Iron plays an important role in cell growth and metabolism. In preneoplastic liver nodules, a rise in the number of transferrin receptors (Tf‐R) is associated with decreased endocytosis of the Fe2‐Tf/Tf‐R complex. Because nodules are precursors of hepatocellular carcinoma (HCC), the question arises whether changes in iron uptake by nodules persist in HCC.

Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis

Martin D. Weltman, Geoffrey C. Farrell, Pauline Hall, Magnus Ingelman‐Sundberg, Christopher Liddle – 30 December 2003 – Nonalcoholic steatohepatitis (NASH) has multiple etiologic associations, but the pathogenesis is poorly understood. Cytochrome P450 (CYP) 2E1 is induced in the liver of patients who drink alcohol to excess and is important in the pathogenesis of alcoholic liver disease (ALD). We have previously shown that hepatic CYP2E1 is also increased in a rat dietary model of steatohepatitis.

Q‐T interval prolongation in cirrhosis: Prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors

Mauro Bernardi, Salvatore Calandra, Alessandra Colantoni, Franco Trevisani, Maria L. Raimondo, Giuseppe Sica, Filippo Schepis, Marina Mandini, Patrizia Simoni, Manuela Contin, Giovanni Raimondo – 30 December 2003 – Prolonged Q‐T interval predicts severe arrhythmias and sudden death, and has been shown to occur in alcoholic liver disease and cirrhotic patients who are candidates for liver transplantation.

Therapy of hepatitis C: Interferon alfa‐2a trials

W M Lee – 30 December 2003 – Interferon alfa‐2a resembles other recombinant α interferons in structure and pharmacology. Studies delineating its efficacy suggest that after 6 to 12 months of therapy, sustained biochemical responses occur in 4% to 49% of patients, providing adequate doses (> or = 3 million units three times weekly) are used. Overall, a dose‐response curve is evident in regard to biochemical responses, decrease in histological scores for inflammation, and virological responses (percent negative serum hepatitis C virus [HCV] RNA) after treatment.

Management of hepatitis C: A national survey of gastroenterologists and hepatologists

J E Everhart, M Stolar, J H Hoofnagle – 30 December 2003 – A survey on the management of hepatitis C virus (HCV) infection was conducted by the American Digestive Health Foundation among United States physicians who are most familiar with the disease. The two‐page survey was completed by 57% of a random sample of 2,500 members of the American Gastroenterological Association and the American Association for the Study of Liver Diseases. Analysis was limited to the 1,249 responses from physicians who spent at least 1 day per week in patient care.

Epidemiology of hepatitis C

M J Alter – 30 December 2003 – In the United States, the annual number of newly acquired acute hepatitis C virus (HCV) infections has declined from an estimated 180,000 in the mid 1980s to an estimated 28,000 in 1995. Approximately 25% to 30% of these infections are clinically apparent cases that are sufficiently symptomatic to gain medical attention. Deaths from fulminant hepatitis C are rare.

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