ABSTRACT
Bile salts in the intestinal lumen act to inhibit the release of cholecystokinin (CCK). Recent studies have shown that CCK may play a permissive role in the development of acute pancreatitis. In this study, the amount of luminal bile salts in female Swiss Webster mice was either decreased by feeding 4% (wt/wt) cholestyramine or increased by feeding 0.5% sodium taurocholate for 1 wk. Plasma levels of CCK were stimulated by cholestyramine and inhibited by taurocholate. Then, acute pancreatitis was induced either by caerulein injections, or by feeding a choline-deficient, ethionine-supplemented (CDE) diet. Feeding of cholestyramine significantly decreased survival from 25% to 0% in the CDE pancreatitis, and increased the magnitude of elevation of serum amylase levels and the extent of pancreatic necrosis in both models of pancreatitis; CCK-receptor blockade with CR-1409 completely abolished the adverse effects of cholestyramine. In contrast, feeding of taurocholate significantly increased survival to 100% and decreased the elevation of serum amylase and pancreatic necrosis; CCK-8 antagonized these actions of taurocholate. Luminal bile salts appear to provide a physiologic protection against necrotizing pancreatitis, at least in part, both by inhibiting the release of CCK and by promoting resistance of the pancreas to CCK excessive stimulation in vivo.
Subject(s)
Bile Acids and Salts/physiology , Pancreatitis/drug therapy , Acute Disease , Amylases/blood , Animals , Ceruletide/pharmacology , Cholecystokinin/blood , Cholestyramine Resin/administration & dosage , Choline Deficiency/physiopathology , Feedback , Female , Mice , Pancreatitis/pathology , Taurocholic Acid/administration & dosageABSTRACT
Some cholesterol gallstones contain darkly pigmented centers or peripheral concentric pigmented bands. We examined the cross-sectional surface of three cholesterol gallstones which contained both central and peripheral pigmented areas with electron-probe microanalysis (EPM) and energy dispersive x-ray microanalysis (EDXA) to determine the elemental composition of the pigmented regions. Linear EPM across the cross-sectional surface of the stones demonstrated that most of the pigmented regions of all three stones had high Ca and P signals; the non-pigmented intervening areas had markedly lower or no detectable Ca and P signals. In two of the three stones, high O signals coincided with the high Ca and P signals suggesting that both calcium bilirubinate and calcium phosphate were present in these pigmented areas. EDXA of the central and peripheral pigmented areas of each stone confirmed the presence of a high Ca signal. Our results demonstrate that in some cholesterol gallstones there is cyclic deposition of calcium bilirubinate and other calcium salts.
Subject(s)
Bile Acids and Salts/analysis , Calcium/metabolism , Cholelithiasis/etiology , Cholesterol/physiology , Calcium/analysis , Cholelithiasis/metabolism , Cholelithiasis/physiopathology , Copper/analysis , Electron Probe Microanalysis , Humans , Oxygen/analysis , Phosphorus/analysisABSTRACT
Sixty patients with mild to moderate upper-gastrointestinal bleeding were admitted to a prospective, controlled study of diagnosis and management, and were randomized to endoscopy or upper-gastrointestinal (UGI) barium series as the initial study. Definitive localization of the source of bleeding was made initially in 69% of the endoscopy group and 21% of the UGI group (P less than 0.0005). Of 54 patients undergoing both studies, endoscopy was definitive in 67% and UGI series in 22%. Thus, endoscopy also made more diagnoses when used as the second study (P less than .01). The use of endoscopy as the initial procedure led to significantly more rapid diagnosis than with UGI series. However, there were no significant differences between the two groups in clinical outcome. Endoscopy is the initial diagnostic procedure of choice in patients with mild to moderate upper-gastrointestinal bleeding because it enables detection of superficial bleeding lesions and has significantly increased the speed of diagnosis.