title: Protective effect of a cephalosporin, Shiomarin, plus a new potent protease inhibitor, E3123, on rat taurocholate-induced pancreatitis.
abstract: The role of infectious factors in the pathogenesis of acute pancreatitis and the protective effect of combined therapy with a new potent synthetic protease inhibitor, E3123, and a new potent synthetic cephalosporin, Shiomarin were examined in rat acute pancreatitis. Sodium taurocholate injection into the pancreatico-biliary duct of rats caused severe pancreatitis with a high mortality rate, characterized by hyperamylasaemia, high amylase activity in ascitic fluid, hyperendotoxaemia and a high serum level of fibrin degradation products (FDP) and redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. Sodium taurocholate injection into the pancreatico-biliary duct also caused the bacterial growth in the pancreas. In rats with E3123 infusion almost all parameters were improved, including mortality rate, serum and ascitic fluid amylase levels, plasma endotoxin and serum FDP levels, and distribution of lysosomal enzyme. But combination therapy with E3123 and Shiomarin was significantly more protective than E3123 therapy alone. These results indicate that infection plays an important role in the development of severe pancreatitis and that combination therapy with a new synthetic protease inhibitor and a new potent antibiotic may be useful in the treatment of severe pancreatitis.
authors.affiliation: First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: T
authors.initials: T
authors.lastname: Manabe
authors.forename: K
authors.initials: K
authors.lastname: Imanishi
authors.forename: T
authors.initials: T
authors.lastname: Tobe
mesh_terms: D000208:Acute Disease; D000818:Animals; D004359:Drug Therapy, Combination; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009070:Moxalactam / Q000008:administration & dosage / Q000627:therapeutic use*; D010195:Pancreatitis / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013656:Taurocholic Acid
chemical_list: D006146:Guanidines; D015842:Serine Proteinase Inhibitors; C057059:4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate; D013656:Taurocholic Acid; D009070:Moxalactam