Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was performed to compare an usual method of induction of acute experimental pancreatitis with a simplified, easier and faster induction through a subcutaneous and intravenous injection of cerulein, with good reproducibility as compared to the literature. Four groups were studied. In the group I, continuous three hour intravenous injection of 15 micrograms/Kg of cerulein, was given. Group II was a control group with saline infusion. Group III received a subcutaneous injection of 20 micrograms/Kg and an intravenous injection of 20 micrograms/Kg of cerulein one hour later. Group IV was the control group with saline. The results of biochemical measurements, such as tecidual trypsinogen, chimotrypsinogen, proelastase, cathepsin and serum amylase, showed no difference between the two methods. Histologic study revealed edematous pancreatitis in group I and III, with moderate acinar necrose in group III. These results suggest that the proposed simplified method induces enough acute and edematous pancreatitis to allow studies in physiopathology and therapeutics.
 ...
PMID:[Simplified model of induction of experimental acute pancreatitis with a supra-maximal dose of cerulein]. 753 38

Trypsinogen activation peptide (TAP) concentration and alpha 2-macroglobulin-trypsin complex (alpha 2M-T) activity were measured in two experimental models of acute pancreatitis in rats to evaluate the significance of activation of trypsinogen in acute pancreatitis. TAP concentration and alpha 2M-T activity in serum rose significantly in trypsin-taurocholate-induced hemorrhagic acute pancreatitis, while in cerulein-induced edematous acute pancreatitis they did not rise in spite of a similar increase in immunoreactive trypsin. When rats in trypsin-taurocholate-induced pancreatitis were treated by protease inhibitor (FUT-175; nafamostat mesilate; FUT group), alpha 2M-T activity in serum was significantly lower than that in nontreated controls (mean +/- SEM, 20.8 +/- 1.43 U/L in the FUT group vs 79.1 +/- 24.5 in controls; p < 0.01). The survival rate at 24 h was significantly improved in the FUT group compared with the controls (70 vs 43%; p < 0.05). The increase in TAP concentration in the FUT group was similar to that in controls. The TAP concentration in pancreatic tissue at 24 h was significantly (p < 0.01) lower in the survival group (7.8 +/- 0.8 ng/ml) than in the lethal group (25.9 +/- 3.7 ng/ml). Activation of trypsinogen and its subsequent enzyme activity play an important role in the evolution of severe acute pancreatitis.
 ...
PMID:Activation of trypsinogen in experimental models of acute pancreatitis in rats. 754 73

Cholecystokinin (CCK) receptor antagonists have been reported on have an inhibitory effect on acute experimental pancreatitis, but their long-term administration is also reported to block pancreatic regeneration. We examined whether the short-term administration of KSG-504 (KSG), a synthetic CCK-A receptor antagonist, inhibited the regeneration of pancreatic acinar cells after ethionine-induced acute pancreatitis in rats. KSG (50 mg/kg), given 12 times by subcutaneous injection at 6-h intervals, prevented the reduction of protein, amylase, and trypsinogen levels, and the DNA content of the pancreas and facilitated the recovery of these values. Ornithine decarboxylase activity in pancreatic tissue and a 5-bromo-2'-deoxyuridine labeling study indicated that DNA synthesis was accelerated in rats treated with KSG. These findings suggest that the short-term administration of KSG inhibits the development of ethionine-induced acute pancreatitis and facilitates the regeneration of acinar cells.
 ...
PMID:Effects of short-term administration of the CCK receptor antagonist, KSG-504, on regeneration of pancreatic acinar cells in acute pancreatitis in rats. 755 Aug 60

To study the early pathogenesis of acute edematous pancreatitis in dogs, we examined the relationship of pancreatic hyperstimulation with cholecystokinin-8 (10 micrograms/kg/hr intravenously for 6 hr) to alterations in circulating pancreatic enzymes and pancreatic morphology with special reference to trypsinogen activation. Cholecystokinin-8 infusion was associated with increases in plasma amylase, lipase, trypsin-like immunoreactivity, and plasma and urine trypsinogen activation peptide. Pancreatic parenchymal swelling and interlobular and subcapsular fluid accumulations were detected ultrasonographically within 2 hr of cholecystokinin-8. Circulating trypsin-like immunoreactivity and trypsinogen activation peptide in urine reached a peak at 2 and 4 hr, respectively, then declined despite progressive increases in circulating amylase and lipase and intrapancreatic fluid. No significant changes were observed in dogs receiving a saline infusion. This study illustrates that cholecystokinin-8 induces edematous pancreatitis in dogs that is associated with a short-lived burst of trypsinogen activation.
 ...
PMID:Cholecystokinin-8 induces edematous pancreatitis in dogs associated with short burst of trypsinogen activation. 758 82

Extraintestinal trypsinogen activation peptides (TAP) have been shown to correlate with severity of acute pancreatitis in humans as well as in various animal models. Ischemia superimposed on experimental pancreatitis, however, increases acinar cell injury without increasing TAP in plasma. We speculated that TAP generated in the pancreas might not reach the circulation in necrotizing pancreatitis due to decreased pancreatic perfusion. To test the hypothesis that generation of TAP in plasma is related to pancreatic perfusion and that plasma TAP may therefore underestimate acinar cell injury in necrotizing disease, we correlated TAP in pancreatic tissue and body fluids with capillary pancreatic blood flow in necrotizing and edematous pancreatitis. The ratio between necrosis and TAP in tissue was similar in both models; the ratio between TAP in plasma and tissue, however, was significantly lower in necrotizing pancreatitis, indicating that a certain amount of TAP generated in the pancreas did not reach the circulation. Decreased pancreatic perfusion found in necrotizing pancreatitis was consistent with this finding. Our data suggest that TAP in tissue is most reliable to indicate severity of acute pancreatitis, whereas plasma TAP may underestimate pancreatic injury in necrotizing disease due to decreased pancreatic perfusion.
 ...
PMID:Effect of microcirculatory perfusion on distribution of trypsinogen activation peptides in acute experimental pancreatitis. 758 86

Calcium antagonists may limit experimental tissue injury by membrane stabilization. We studied the effects of verapamil on pancreatic ultrastructure and zymogen extraction during diet-induced acute pancreatitis. Acute pancreatitis was induced in female Swiss-Webster mice by feeding a choline- and methionine-deficient diet (CD) supplemented with 1% ethionine (CDE). Varying doses of verapamil in normal saline were infused continuously at a rate of 0.5 microliter/hr for 96 hr through subcutaneously implanted osmotic pumps. The pancreata were examined blindly by light microscopy and by electron microscopy. Zymogen extracted from pancreatic tissue was measured and expressed per gram of protein. Mean histological scores, calculated according to a formula that incorporates the extent of necrosis, inflammation, acidophilia, and edema, were 14.1 +/- 4, 10.3 +/- 2, 9.9 +/- 4, 5.9 +/- 7, 12.5 +/- 4, and 12.7 +/- 4 for CDE-fed animals receiving 0, 0.14, 0.28, 0.56, 0.84, and 1.12 microM verapamil daily, respectively. Animals fed normal diet or CD had scores of 0 +/- 0. Histological scores were significantly lower in animals treated with 0.56 microns verapamil compared to animals who received no verapamil (p < 0.05) and was associated with reduced dissolution of the zymogen granule membrane on EM. Mean extracted trypsinogen and chymotrypsinogen content were reduced in the CD- and CDE-fed mice. The reduction in mean trypsinogen content reached statistical significance in CDE-fed mice treated with verapamil 0.56 microM daily. Mean chymotrypsinogen content was also significantly reduced CD-mice and in mice treated with 0.56 microns and 0.84 microM of verapamil daily. Increasing doses of verapamil protect against diet-induced pancreatitis in mice.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Dose-dependent effect of continuous subcutaneous verapamil infusion on experimental acute pancreatitis in mice. 758 13

Acinar necrosis in patients with acute pancreatitis can be due to enzymatic injury, ischemia, or both. We hypothesized that novel therapy aimed at an improvement of pancreatic microcirculation early in the course of pancreatitis may reduce the lethality and acinar damage. Forty-six dextran-resistant rats received controlled intraductal infusion of glycodeoxycholic acid (10 mmol/L), followed by intravenous cerulein (5 micrograms/kg/h) for 6 hours. Beginning 30 minutes after the induction of pancreatitis, all animals were resuscitated with Ringer's lactate (RL) (8 mL/kg/h intravenously for 9 hours). In addition, they were given intra-aortic bolus infusions (2 mL/kg at 30, 60, 90, and 150 minutes) of either RL, sodium chloride (NaCl) (7.5%) and dextran 60,000 (10%) (HHS-60), NaCl (7.5%) and dextran 500,000 (10%) (HHS-500), or NaCl (0.9%) and dextran 500,000 (10%) (DEX-500). Despite high-volume fluid resuscitation in the groups that received RL and HHS-60, 70% of the animals in each of these groups died within 24 hours. In contrast, the mortality rates in the groups of animals that received HHS-500 and DEX-500 were dramatically reduced to 0% and 10%, respectively (p = 0.005, p = 0.02). Histopathologic scores for acinar necrosis were significantly lower in the group of animals that received DEX-500 (p < 0.009) compared with those that received RL and HHS-60. Finally, total amounts of trypsinogen activation peptides in ascites were significantly lower in the animals that received HHS-500 (p < 0.004) and DEX-500 (p < 0.02) compared with those that received RL and HHS-60. Rapid bolus infusion of hyperoncotic ultrahigh molecular weight dextran solution with or without hypertonic saline but not RL or hypertonic-hyperoncotic saline-dextran significantly reduced pathologic trypsinogen activation, prevented acinar necrosis, and improved survival in acute experimental pancreatitis. We speculate that a sustained improvement of pancreatic microcirculation by ultrahigh molecular weight dextran is the mechanism of action.
 ...
PMID:Hyperoncotic ultrahigh molecular weight dextran solutions reduce trypsinogen activation, prevent acinar necrosis, and lower mortality in rodent pancreatitis. 767 89

Recent investigations have suggested that digestive zymogens may become activated within the acinar cell during acute pancreatitis. While the molecular events responsible for intracellular zymogen activation remain unknown, several potential enzymatic pathways require an acidic pH to optimally proceed. We therefore proposed that manipulation of subcellular pH might alter the course of experimental pancreatitis. Chloroquine, a weak base that raises the pH of acidic subcellular compartments, was administered to young female mice in which pancreatitis was induced by a choline-deficient, ethionine-supplemented (CDE) diet. Control animals were maintained on regular laboratory chow. Examination of isolated pancreatic acini using acridine orange cytofluorescence demonstrated expansion of acidic subcellular compartments in animals fed the CDE diet. These compartments were effectively neutralized in animals receiving chloroquine. Animals receiving continuous infusions of high-dose chloroquine demonstrated a significant (p < 0.05) decrease in free pancreatic tryptic activity as well as improved survival. These changes were also associated with decreased trypsinogen content in animals treated with high-dose chloroquine, suggesting an additional potential effect of chloroquine on zymogen synthesis and accumulation. One explanation of these findings is that a low-pH compartment may be important in the pathogenesis of diet-induced pancreatitis.
 ...
PMID:Influence of chloroquine on diet-induced pancreatitis. 767 27

The effects of single and repeated short-term (4 hr) obstruction of pancreaticobiliary duct (PBDO), with or without exocrine stimulation (intraductal hypertension) by cerulein infusion (0.2 micrograms/kg.hr), on the exocrine pancreas were evaluated in the rat. Single blockage of pancreaticobiliary duct for 4 hr caused a significant rise in serum amylase levels, pancreatic water content, and redistribution of lysosomal enzyme, cathepsin B from the lysosomal fraction to the zymogen fraction, which was considered to mean the colocalization of lysosomal enzymes with pancreatic digestive enzymes in the same subcellular compartment in acinar cells. In addition, the accelerated lysosomal and mitochondrial fragility was observed in the single pancreaticobiliary-duct-obstructed animals. Moreover, the repeated PBDO for 4 hr (2 hr in each obstruction and 1 hr of free flowing of pancreaticobiliary juice between two obstructions) caused more marked changes in almost the all parameters, and the repeated PBDO with intraductal hypertension caused an activation of trypsinogen in the pancreas, making more marked changes in almost the all parameters than the repeated PBDO only group. These results indicate that the present model of repeated PBDO with exocrine stimulation seems to be a pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries induced by PBDO, particularly by repeated PBDO with exocrine stimulation, probably via activation of trypsinogen to trypsin by lysosomal enzyme, cathepsin B.
 ...
PMID:A possible mechanism for gallstone pancreatitis: repeated short-term pancreaticobiliary duct obstruction with exocrine stimulation in rats. 767 5

The redistribution of cathepsin B, a representative lysosomal enzyme, from the lysosomal pellet to the zymogen pellet in subcellular fractions and the colocalization of cathepsin B with digestive enzymes within acinar cells have been found during the early stage of caerulein-induced acute pancreatitis in the rat. This study investigated the protective effects of prostaglandins E1 and E2 on the exocrine pancreas in this experimental pancreatitis. Prostaglandin E2, but not E1, prevented the redistribution of cathepsin B along with the hyperamylasemia, and the increase in amylase and trypsinogen in the acinar cells in almost a dose-dependent manner, particularly at a dose of 100 micrograms/kg.hr of continuous infusion. These results suggest that subcellular organelle fragility is closely related to the pathogenesis of acute pancreatitis, and that prostaglandin E2 has an important cytoprotective effect on biological membranes as a stabilizer of lysosomal membrane.
 ...
PMID:Effect of prostaglandin E on the redistribution of lysosomal enzymes in caerulein-induced pancreatitis. 768 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>