Methods Ethical approval and study design The present www.selleckchem.com/products/ganetespib-sta-9090.html study was approved by the University of Auckland Animal Ethics Committee. Twenty-eight male Wistar rats (6�C8 months old, 463 �� 2 g; mean �� SEM), fed a standard Harlan Teklad 2018 rodent diet (Madison, WI, USA) were randomised to four groups: Group 1 (n = 8), saline control; Group 2 (n = 6), caerulein-induced acute pancreatitis (CIP); Group 3 (n = 7) sham surgical controls (laparotomy only without induction of pancreatitis); and Group 4 (n = 7), taurocholate-induced acute pancreatitis (TIP, a laparotomy followed by intraductal infusion of taurocholate into the pancreas).18,19 All chemicals used in these experiments were supplied by Sigma Aldrich Pty Ltd (New South Wales, Australia), unless otherwise stated.

Caerulein-induced pancreatitis model Mild CIP was induced by four subcutaneous (s.c.) injections of 20 ��g/kg caerulein, a cholecystokinin analogue, in a total of 0.8 ml of 0.9% NaCl at hourly intervals.20,21 Analgesia was by buprenorphine (0.05 ��g/kg, s.c.; Temgesic ?, Reckitt and Coleman, Hull, England). Saline controls were treated with 0.9% NaCl (normal saline) s.c. only. Taurocholate-induced pancreatitis model Balanced general anaesthesia was induced and maintained by isoflurane (2�C5%; 2 l/min O2 via nasal cone) and buprenorphine (0.05 ��g/kg, s.c.). Body temperature was maintained between 36�C38��C by use of a warming plate. All animals received 5 ml of SC normal saline administered at the start of the experimental protocols, after which the common pancreatic duct was cannulated with a 24-G angiocath passed transduodenally through the Ampulla of Vater through a 1.

5-cm abdominal midline incision. The rostral part of the animal was raised 60�� to the horizontal for 5 min to allow the bile duct system to drain (~0.1 ml). During the last 2 min of this procedure, the common hepatic duct was occluded at the hilum (Biemer atraumatic vascular clip; Aesculap, Center Valley, PA, USA). Sodium taurocholate (4% w/v in 0.9% NaCl; 0.1 ml/100 g BW) was infused at 0.1 ml/min by a controlled infusion pump (Genie Precision Pump; Kent Scientific, Torrington, CT, USA). The Biemer clip and angiocath were removed upon completion of the infusion, and the common pancreatic duct was ligated to prevent reflux of taurocholate into the duodenum. The abdomen was then closed and the rat recovered on a warming plate. In the post-operative phase, all animals were individually housed, had access to food and tap water ad libitum for 6 h and were monitored as per a standard post-operative recovery protocol; thereafter, they were rapidly Drug_discovery anaesthetised under isoflurane.