title: Targeted inhibition of pancreatic acinar cell calcineurin is a novel strategy to prevent post-ERCP pancreatitis.
abstract: OBJECTIVE
  There is a pressing need to develop effective preventative therapies for post-ERCP pancreatitis (PEP). We demonstrated that early PEP events are induced through the calcium-activated phosphatase calcineurin and that global calcineurin deletion abolishes PEP in mice. A crucial question is whether acinar cell calcineurin controls the initiation of PEPin vivo.
  
  
  METHODS
  We used a mouse model of PEP and examined the effects ofin vivoacinar cell-specific calcineurin deletion by either generating a conditional knockout line or infusing a novel AAV-Ela-iCre into the pancreatic duct of a calcineurin floxed line.
  
  
  RESULTS
  We found that PEP is dependent on acinar cell calcineurinin vivo, and this led us to determine that calcineurin inhibitors, infused within the radiocontrast, can largely prevent PEP.
  
  
  CONCLUSIONS
  These results provide impetus for launching clinical trials to test the efficacy of intraductal calcineurin inhibitors to prevent PEP.
authors.affiliation: Department of Pediatric GI, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Abrahim I
authors.initials: AI
authors.lastname: Orabi
authors.affiliation: Department of Pediatric GI, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Pediatric GI, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Tanveer A
authors.initials: TA
authors.lastname: Javed
authors.affiliation: Department of Pediatric GI, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Tianming
authors.initials: T
authors.lastname: Le
authors.affiliation: Department of Pediatric Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Ping
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Pediatric GI, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Sanker
authors.affiliation: Department of Pediatric Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: David
authors.initials: D
authors.lastname: Ricks
authors.affiliation: Department of Pediatric GI, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Kristy
authors.initials: K
authors.lastname: Boggs
authors.affiliation: Department of Pediatric GI, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: John F
authors.initials: JF
authors.lastname: Eisses
authors.affiliation: Magee-Womens Research Institute of the University of Pittsburgh Medical Center, Pittsburgh, PA, 15213.
authors.forename: Carlos
authors.initials: C
authors.lastname: Castro
authors.affiliation: Department of Pediatric Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pediatric Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasadan
authors.affiliation: Department of Pediatric Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Farzad
authors.initials: F
authors.lastname: Esni
authors.affiliation: Department of Pediatric Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: George K
authors.initials: GK
authors.lastname: Gittes
authors.affiliation: Department of Pediatric GI, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224.
authors.forename: Sohail Z
authors.initials: SZ
authors.lastname: Husain
keywords: Cyclosporine A; FK506; adeno-associated virus; calcineurin B1; intraductal delivery