Synergistic inhibition of hepadnaviral replication by lamivudine in combination with penciclovir in vitro

D Colledge, S Locarnini, T Shaw – 30 December 2003 – Lamivudine ([‐]‐β‐L‐2′,3′‐dideoxy‐3′‐thiacytidine [3TC]) and penciclovir (9‐[2‐hydroxy‐1‐(hydroxymethyl)ethoxymethyl]guanine [PCV]) are potent inhibitors of hepatitis B virus (HBV) replication. Both drugs have entered phase III clinical trials for treatment of chronic HBV infection. 3TC and PCV are deoxycytidine and deoxyguanosine analogs, respectively, and their modes of action and how they interact are matters of both theoretical and practical interest.

Nitric oxide formation lowers norepinephrine‐induced intrahepatic resistance without major effects on the metabolism in the perfused rat liver

H Weidenbach, A K Nussler, Z Shu, G Adler, K Beckh – 30 December 2003 – Nitric oxide (NO) and norepinephrine are potent vasoactive agents that are involved in the control of portal blood flow. We have studied NO and norepinephrine in a non‐recirculated rat liver perfusion to analyze their influence on portal flow and hepatic metabolism. Animals were either pretreated with endotoxin (4 hours; 10 mg/kg intraperitoneally) to activate the inducible NO synthase (NOS2), or used without pretreatment for the constitutive NO synthase (NOS3).

Intestinal absorption and enterohepatic cycling of biliary iron originating from plasma non‐transferrin‐bound iron in rats

P Brissot, U Bolder, C D Schteingart, J Arnaud, A F Hofmann – 30 December 2003 – In iron overload, non‐transferrin‐bound iron (NTBI) is found in plasma and is rapidly removed by hepatocytes. Some of this NTBI is excreted into bile. Biliary excretion of NTBI, in the form of an iron‐ deferiprone chelate, is greatly increased by deferiprone, an iron chelator. The aim of this study was to test whether biliary iron as such or as an iron‐deferiprone chelate (both originating from plasma NTBI) is absorbed from the intestine and re‐secreted into bile.

Prevalence of hereditary hemochromatosis in a Massachusetts corporation: Is Celtic origin a risk factor?

B N Smith, W Kantrowitz, N D Grace, M S Greenberg, T J Patton, R Ookubo, K Sorger, J G Semeraro, J R Doyle, A G Cooper, B R Kamat, L M Maregni, W M Rand – 30 December 2003 – The prevalence of homozygous hereditary hemochromatosis (HHC) is estimated at 1:250 in Caucasian adults. Little is known about ethnic subpopulations that might be at increased risk for this disease. HLA data have suggested a Celtic origin for HHC. Screening for HHC was offered to all employees of the Massachusetts Polaroid Corporation.

Effect of taurohyodeoxycholic acid on biliary lipid secretion in humans

P Loria, M Bozzoli, M Concari, M E Guicciardi, F Carubbi, M Bertolotti, D Piani, A Nistri, M Angelico, M Romani, N Carulli – 30 December 2003 – This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6α‐hydroxylated bile acid with hydrophilic properties, on bile lipid secretion. Four cholecystectomized patients who had gallstones and an interrupted enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h for 3 hours.

Hepatitis G virus co‐infection in liver transplantation recipients with chronic hepatitis C and nonviral chronic liver disease

M W Fried, Y E Khudyakov, G A Smallwood, M Cong, B Nichols, E Diaz, P Siefert, K Gutekunst, R D Gordon, T D Boyer, H A Fields – 30 December 2003 – Hepatitis G virus (HGV) is a newly described RNA virus that is parenterally transmitted and has been found frequently in patients with chronic hepatitis C infection.

Association of seropositivity for hepatitis viruses and aplastic anemia in Thailand

S Issaragrisil, D Kaufman, A Thongput, K Chansung, T Thamprasit, A Piankijagum, T Anderson, S Shapiro, P Leaverton, N S Young – 30 December 2003 – Aplastic anemia is more common in the Orient than in western countries, with an incidence in Thailand that is 2‐ to 3‐fold higher than in Europe. Aplastic anemia after hepatitis is a well characterized clinical entity, and clinical hepatitis is also prevalent in the Far East. We performed a prospective case‐control study to determine risk factors for aplastic anemia in Bangkok and two rural regions during 1989 to 1994.

Hrp12, a novel heat‐responsive, tissue‐specific, phosphorylated protein isolated from mouse liver

S J Samuel, S P Tzung, S A Cohen – 30 December 2003 – Previous studies from this laboratory identified a 28‐kd nonreducible protein, liver‐derived immunoinhibitory factor (LDIF) from the mouse liver. Isolation of this protein resulted in the co‐purification of another unique protein called heat responsive protein 12 kd (Hrp12). In contrast to LDIF, Hrp12 was totally reducible to a protein of 12 kd suggesting a dimer.

Reperfusion after liver transplantation in rats differentially activates the mitogen‐activated protein kinases

C A Bradham, R F Stachlewitz, W Gao, T Qian, S Jayadev, G Jenkins, Y Hannun, J J Lemasters, R G Thurman, D A Brenner – 30 December 2003 – The injury resulting from cold ischemia and warm reperfusion during liver transplantation is a major clinical problem that limits graft success. Kupffer cell activation plays a pivotal role in reperfusion injury, and Kupffer cell products, including free radicals and tumor necrosis factor α (TNF‐α), are implicated as damaging agents.

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