Gallbladder disease is an important human condition causing significant pain and suffering. While stone formation is an evident contributor to the process, the human gallbladder is prone to develop inflammation. The human gallbladder commonly becomes inflamed and requires removal in the absence of gallstones. Previous research has demonstrated the potential of delineating the chemical mechanisms resulting in cholecystitis. Prostaglandin F2Alpha is present in bile in concentrations 10 times those found in plasma. Nanogram quantities of prostaglandin E and F are present in animal and human gallbladder tissue. Recent evidence demonstrates specific increases in prostaglandin E content as human gallbladder inflammation increases. Prostaglandin synthetase inhibition can alter prostaglandin formation in animal and human gallbladders and decrease experimental inflammation. The research is directed at further delineating the biochemical basis of cholecystitis and providing methods of treating the pain of cholecystitis and of preventing and controlling the inflammatory process. Progressive characterization of the prostaglandin content in animal and human gallbladders with and without inflammation appears to be essential. High performance liquid chromatography techniques have the ability to identify specific prostaglandins in bile, gallbladder muscle, and gallbladder mucosa. Similarly, current therapeutic use of inhibition of prostaglandin synthetase, and the cyclooxygenase system to treat cholecystitis pain may increase the activity of the lipoxygenase system and enhance rather than decrease inflammation. We are compelled to ascertain the role of the leukotrienes in cholecystitis. Gallbladder stones and inflammation evoke severe pain responses. The proposed research will utilize algesics to study the pharmacology of the pain response in gallbladder tissue with the potential of extrapolation of this information to enhance analgesia in biliary tract pain. The susceptibility of the gallbladder to become inflammed may be related to deficiencies in anti-inflammatory substances in bile or biliary tissue. The research is directed at evaluating the kinin system in bile and gallbladder tissue. Pathologic inflammation develops with activation of the kinin system and accentuated responses may be due to increased kinin activity or lack of inhibitory kinase activity. The proposed research will ascertain the role the kinin system plays in cholecystitis. The control of inflammation and pain in cholecystitis may eventuate from a better understanding of the biochemical mechanisms producing these processes.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Surgery and Bioengineering Study Section (SB)
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Saint Louis University
Schools of Medicine
Saint Louis
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