The proposed studies will explore the cell biology of several different experimental forms of acute pancreatitis, identify factors which favor the worsening of mild forms of pancreatitis, and test several potential therapies for acute pancreatitis. These studies will build upon and are the natural extension of many investigations already completed by our group which have suggested that intracellular activation of digestive enzyme zymogens by lysosomal hydrolases may be an important triggering event in pancreatitis. To accomplish the goals of these studies, a number of experimental model systems will be selectively employed. These include the diet-induced, secretagogue-induced, and opossum duct ligation models of acute pancreatitis. The effect of ligating the rat pancreatic duct and of obstructing flow in the rabbit pancreatic duct and of supramaximal in-vitro stimulation of rat pancreatic lobules will be studied. This will be a highly collaborative effort in which biochemical-cell physiological studies will be undertaken in Boston by the P.I. while morphological and fluorescence microscopy studies will be performed by a co-investigator in Milan. It can be expected that these studies will greatly expand our understanding of the cell biology of acute pancreatitis and suggest strategies by which this disease can be treated and/or prevented.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37DK031396-07
Application #
3483608
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1982-07-01
Project End
1993-11-30
Budget Start
1988-12-21
Budget End
1989-11-30
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
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Bhagat, Lakshmi; Singh, Vijay P; Song, Albert M et al. (2002) Thermal stress-induced HSP70 mediates protection against intrapancreatic trypsinogen activation and acute pancreatitis in rats. Gastroenterology 122:156-65
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