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

The redistribution of cathepsin B, a lysosomal enzyme, from the lysosomal pellet to the zymogen pellet in the subcellular fractionation, the colocalization of cathepsin B with digestive enzyme, and increased cellular, lysosomal, and mitochondrial fragility within acinar cells have been found during the early stages of caerulein-induced acute pancreatitis in rats. In the present study, the authors investigated the protective effects of prostaglandin E1 and E2, a combined therapy of these prostaglandins, and a new, synthetic, low molecular weight protease inhibitor, ONO3307, on the exocrine pancreas in this noninvasive model of experimental pancreatitis in vivo and in vitro. Prostaglandin E2, but not E1, prevented hyperamylasemia, congestion of amylase and trypsinogen in the acinar cells, redistribution of cathepsin B, and amylase and lactate dehydrogenase discharge from the dispersed acini. It also prevented cathepsin B leakage from the lysosomes and malate dehydrogenase leakage from the mitochondria in an almost dose-dependent manner, particularly at the dose of 100 micrograms/kg/hr continuous infusion. Furthermore, the combined therapy of prostaglandin E2 with ONO3307 strongly inhibited all the parameters tested in this study. This combination therapy seems to be the most effective against secretagogue-induced pancreatic injuries. These results indicate that cellular and subcellular organellar fragility seem to be closely involved in the pathogenesis of acute pancreatitis. Prostaglandin E2 seems to have important cytoprotective effects on the biologic membranes, such as a stabilizer of lysosomal or mitochondrial membranes. In addition, these findings also suggest the crucial roles of some unknown proteases in the etiology of acute pancreatitis, and indicate the clinical effectiveness of prostaglandins and this type of low molecular weight protease inhibitor for acute pancreatitis.
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PMID:Cytoprotective effects of prostaglandins and a new potent protease inhibitor in acute pancreatitis. 128 94

Acute necrotising pancreatitis in rats was induced by injecting 5% sodium taurocholate into the pancreatic duct. Prostaglandin E2 (100 micrograms/kg subcutaneously twice) decreased the mortality rate from 100% to 60% (NS). When treatment with prostaglandin E2 was combined with simultaneous administration of either dazmegrel (UK 38,485, 50 mg/kg bodyweight) or Sibelium (Flunarizine R 14,950, 0.2 mg/kg body weight) a significant decrease in the mortality rate (p less than 0.05) was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and prevents the formation of thromboxane A2. Flunarizine (a calcium entry blocker) decreases thromboxane A2 formation and also inhibits the effects of raised thromboxane A2 concentrations. As plasma thromboxane B2 (the stable metabolite of thromboxane A2) concentrations increase and the plasma prostaglandin E2 concentrations decrease in acute necrotising pancreatitis in rats, the results of the present study indicate that these prostaglandins play a role in the pathophysiology of the disease. It is suggested that restoration of the balance in prostanoid concentrations will have a beneficial effect on the course of acute necrotising pancreatitis.
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PMID:Significance of prostaglandin E2 in acute necrotising pancreatitis in rats. 273 61

Evidence suggests that changes in prostaglandins and disseminated intravascular coagulation accompany pancreatitis. Both may induce changes in platelet function. We wished to determine if experimentally induced pancreatitis in the dog was associated with altered platelet number and function, and whether there were concomitant changes in prostaglandins. Evidence for disseminated intravascular coagulation in the dogs with pancreatitis were red blood cell fragmentation, increased platelet turnover indicated by macro-platelets and the transient presence of fibrin degradation products in urine. There were no significant changes in platelet count. The platelets from dogs with pancreatitis showed a functional defect characterized by significantly decreased aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. Release of adenosine triphosphate from platelets was reduced in collagen-stimulated aggregation. There were no changes in the plasma concentrations of thromboxane B2, 6-Keto-PGF1a, and PGE2. This defect may have been due to the generation of fibrin degradation products and platelet "exhaustion".
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PMID:Platelet function in experimentally induced pancreatitis in the dog. 308 2

CR 1409, a glutaramic acid derivative with competitive cholecystokinin-antagonistic activity, was administered IP and evaluated in comparison with proglumide (the model CCK-receptor antagonist), gabexate (protease inhibitor) and PGE2 (cytoprotective) on two different models of experimental pancreatitis. Acute pancreatitis was induced in mice by six IP injections of 50 micrograms/kg caerulein at hourly intervals. The drugs were administered 30 minutes before each caerulein administration. Blood samples and pancreata were collected 3 hours after the last caerulein injection. In the second experiment, pancreatitis was induced in rats by injecting 0.3 ml 6% sodium taurocholate interstitially into the pancreas. The drugs were administered twice, 30 minutes before and 3 hours after taurocholate. The animals were killed 6 hours after laparotomy and blood samples and pancreata were collected. CR 1409 exhibited on both pancreatitis models a protective effect in a dose range of 0.3-10 mg/kg. Proglumide exhibited a protective activity at higher doses (200-400 mg/kg). Gabexate and PGE2 were effective only in pancreatitis induced by taurocholate in a dose range of 30-60 mg/kg and 60-130 micrograms/kg respectively. These results, showing a high protective effect of CR 1409 on different models of acute pancreatitis, suggest an important role of CCK in the pathogenesis of pancreatitis.
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PMID:Protective effect of CR 1409 (cholecystokinin antagonist) on experimental pancreatitis in rats and mice. 310 90

In an investigation of the pathogenesis of acute necrotizing pancreatitis (ANP) the plasma levels of TXB2, 6-keto-PGF1 alpha, and PGE2 were measured in rats. After induction of ANP by injection of 5% sodium taurocholate into the pancreatic duct, a marked increase in TXB2 levels and a slight increase in 6-keto-PGF 1 alpha levels were found. PGE2 levels decreased. Mortality was 100% within 30 h. Pretreatment with chloroquine, a phospholipase A2 inhibitor, led to a inhibition of TXB2 production, whereas 6-keto-PGF1 alpha and PGE2 levels showed a surprising slight elevation in the first 6 h. Pretreatment with chloroquine decreased mortality by 30%. Pretreatment with FPL 55712, a leukotriene synthesis blocker, caused an increase in TXB2 and PGE2 levels, whereas the formation of 6-keto-PGF1 alpha remained unaltered. Two out of nine animals survived after pretreatment with FPL 55712. The results of the present study indicate that arachidonate end products are involved in ANP. The significance of the high TXB2 levels, decreased PGE2 levels, and only slightly elevated 6-keto-PGF1 alpha levels during ANP requires further investigation. The thromboxane A2 to prostacyclin ratio may be important.
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PMID:Prostanoid imbalance in experimental acute necrotizing pancreatitis in rats. 316 72

Acute pancreatitis can be induced experimentally in rats by the retrograde pancreatic duct injection of deoxycholic acid. In order to evaluate if prostaglandins have a protective or therapeutic role, pancreatitis was induced with 0.03, 0.1, or 0.2 ml of 3% deoxycholic acid. Then, 16,16 dimethyl prostaglandin E2 or prostaglandin I2 were infused i.v. for 30 min before the deoxycholic acid injection or for 1 or 24 h beginning 30 min or 1 h after the injection. Deoxycholic acid, 0.1 and 0.2 ml, produced an 80-100% mortality at 24 h after the induction of pancreatitis, and prostaglandin administration had no appreciable effect. Induction of pancreatitis with 0.03 ml deoxycholic acid was associated with a 15% mortality at 24 h, and both prostaglandins significantly increased the mortality. In the experimental model of pancreatitis tested, the administration of exogenous PGI2 and 16,16 dimethyl PGE2 significantly worsened the outcome.
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PMID:Prostaglandin E2 and I2 treatment of acute experimental pancreatitis in rats. 355 Jul 89

In a model of acute pancreatitis which requires that pancreatic enzymes leak from a permeable duct, we studied the role of intravenous enterokinase (195,000 daltons) in pancreatic enzyme activation. Anesthetized cats were given intravenous 16,16-dimethyl prostaglandin E2 to increase pancreatic blood flow and microvascular permeability. In some animals the permeability of the pancreatic duct was increased by perfusion of the duct with glycodeoxycholic acid (7.5 mM). Endogenous enzyme secretion was stimulated by IV CCK and secretin. Some cats also received enterokinase intravenously. Those animals that received PGE2, glycodeoxycholate, and enterokinase all developed pancreatitis. When any of these agents were not given the pancreases appeared normal. These findings were consistent with the hypothesis that intravenous enterokinase leaked from small pancreatic blood vessels into the pancreatic parenchyma and/or ducts where activation of pancreatic enzymes occurred. The development of pancreatitis appeared to require an increase in both microvascular and ductal permeability.
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PMID:Pancreatic duct and microvascular permeability to macromolecules. The relation to acute pancreatitis. 385 17

Pharmacological attempts to alter the course of experimental pancreatitis in the opossum were made using synthetic 16, 16-dimethyl prostaglandin E2 (16, 16-dm PGE2). Anatomically, the opossum has an elongated ampulla resulting in a supraduodenal pancreatic duct-common bile duct junction allowing for bile reflux pancreatitis to be produced by ligating the distal common bile duct. Preliminary evaluation demonstrated that at 72 hours common bile duct ligation distal to the pancreatic duct orifice produced pancreatitis comparable in severity to that produced by a Pfeffer loop. When the oppossum distal common bile duct was ligated, serum amylase concentrations progressively increased from control values of 182 +/- 43 to 742 +/- 62 Somogyi units/dl at 5 hours. Administration of 0.2 microgram-kg-1-min-1 16, 16-dm PGE2 significantly decreased the hyperamylasemia associated with bile reflux pancreatitis and, in addition, decreased the pancreatic gland weights when compared to control values. Subsequent evaluation of the administration of 75 micrograms-kg-1 16, 16-dm PGE2 every 12 hours for 72 hours to opossums with distal common bile duct ligation demonstrated no significant differences in serum amylase concentrations when compared to control values. Histologic evaluation of the pancreas glands at 72 hours demonstrated increased glandular integrity when the pancreas glands from the opossums receiving 16,16-dm PGE2 were compared to the glands subjected to distal common bile duct ligation alone. This report identifies several favorable characteristics in the course of experimental pancreatitis associated with the administration of a synthesis PGE analog at the onset of the inflammatory process.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of 16, 16-dimethyl prostaglandin E2 on experimental bile reflux pancreatitis in the opossum. 608 98

Prostaglandins have been reported to exert a protective effect against short-term experimental pancreatic injury. We evaluated the protective effect of PGE2 using a model designed to maintain pancreatitis over a period of 5-10 days. Acute pancreatitis was induced by daily intraperitoneal injections of DL-ethionine in rats maintained on a protein-free diet. Test periods of 10 and 5 days (parts I and II, respectively) were employed. In parts I and II, PGE2 0.1 microgram/g body wt was given subcutaneously 30 min before ethionine. In part II, a second daily dose of PGE2 0.1 microgram/g body wt was given 7 h after ethionine. PGE2 did not protect against the weight loss, decrease in food consumption, alteration in serum amylase, pancreatic necrosis, or mortality induced by ethionine. This study indicates that the protective effect of PGE2 observed in short-term experimental pancreatitis is not reproducible in a model in which pancreatitis is maintained for 5 and 10 day periods.
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PMID:The effect of prostaglandin E2 on ethionine-induced pancreatitis in the rat. 616 85

Prostaglandin E2 (PGE2) is known to have a cytoprotective effect on the gastric mucosa exposed to a variety of noxious agents. A cytoprotective effect on the pancreas in acute pancreatitis has been postulated, but available evidence is contradictory. Acute experimental pancreatitis was induced in 170 male Wistar rats by retrograde injection of 0.6 ml of 5% Na-taurocholate into the pancreatic duct. PGE2 (0.1 microgram/g rat) was given intraductally, intraperitoneally or subcutaneously before and after induction of pancreatitis. PGE2 had no effect on survival rate, enzyme levels in serum and ascites, or on morphologic damage to the pancreas.
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PMID:Does PGE2 have a beneficial effect on acute experimental pancreatitis in the rat? 657 98


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