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Titolo:
Activated protein C prevents multiple organ injury following extensive hepatectomy in cirrhotic rats
Autore:
Yoshikawa, A; Kaido, T; Seto, S; Katsuura, Y; Imamura, M;
Indirizzi:
Kyoto Univ, Grad Sch Med, Dept Surg & Surg Basic Sci, Sakyo Ku, Kyoto 6068507, Japan Kyoto Univ Kyoto Japan 6068507 Basic Sci, Sakyo Ku, Kyoto 6068507, Japan Teijin Ltd, Pharmaceut Dev Res Labs, Tokyo, Japan Teijin Ltd Tokyo Japan eijin Ltd, Pharmaceut Dev Res Labs, Tokyo, Japan
Titolo Testata:
JOURNAL OF HEPATOLOGY
fascicolo: 6, volume: 33, anno: 2000,
pagine: 953 - 960
SICI:
0168-8278(200012)33:6<953:APCPMO>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
MASSIVE HEPATIC-NECROSIS; HUMAN ENDOTHELIAL-CELLS; DOWN-REGULATION; TISSUE FACTOR; THROMBOMODULIN; THROMBIN; ANTICOAGULANT; COAGULATION; LIVER; PRETREATMENT;
Keywords:
activated protein C; cirrhosis; extensive hepatectomy; ICAM-1; multiple organ injury; tumor necrosis factor-alpha;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Kaido, T Kyoto Univ, Grad Sch Med, Dept Surg & Surg Basic Sci, Sakyo Ku, 54 Shogoin, Kyoto 6068507, Japan Kyoto Univ 54 Shogoin Kyoto Japan 6068507 , Kyoto 6068507, Japan
Citazione:
A. Yoshikawa et al., "Activated protein C prevents multiple organ injury following extensive hepatectomy in cirrhotic rats", J HEPATOL, 33(6), 2000, pp. 953-960

Abstract

Background/Aims: Extended hepatectomy for cirrhotic liver in patients withhepatocellular carcinoma often triggers posthepatectomy liver failure. It has been shown that the microcirculatory disturbance caused by microthrombus formation and sinusoidal endothelial cellular injury is one of the causesof posthepatectomy liver dysfunction, We therefore investigated the effectof activated protein C (APC), a potent antithrombotic serine protease withanti-inflammatory effects, on posthepatectomy liver dysfunction and multiple organ injury in, cirrhotic rats. Methods/Results: Dimethylnitrosamine-induced cirrhotic rats underwent 70% hepatectomy and received lipopolysaccharide (200 mug/kg) 48 h later to prepare a lethal posthepatectomy acute liver failure model. APC (1500 U/kg), given intravenously 15 min before and 1 h after endotoxin challenge, attenuated liver dysfunction and decreased serum tumor necrosis factor-alpha concentration, APC significantly improved the survival rate of rats at 12 h afterendotoxin challenge. Histological examination revealed that APC treatment inhibited not only intrasinusoidal fibrin deposition and massive hepatocellular necrosis but also pulmonary injury and glomerular fibrin deposition. Immunohistochemically, expression,of intercellular adhesion molecule-1 on sinusoidal cells and renal glomeruli was decreased in the APC-treated animals. Conclusions: APC administration prevented acute liver dysfunction and attenuated multiple organ injury following extended hepatectomy in cirrhotic rats, possibly via anticoagulant and anti-inflammatory effects.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 17:41:09