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 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

Effects of prostaglandin E (PGE) on acute pancreatitis have been controversial. This study shows the effects of PGE1 oligomer, MR-356, on trypsin-taurocholate-induced acute pancreatitis in rats. Divided intraperitoneal doses of 0.6 mg/rat were administered, which increased 24 h survival rates when the oligomer was given both at 1 h before and after (group A) and immediately and 3 h after (group B) induction of pancreatitis. In group A MR-356 significantly improved the survival rates at 18 h (94 vs 61%, P < 0.05) and 24 h (68 vs 33%, P < 0.05) when compared with controls. MR-356 improved the survival rates dose-dependently up to 0.6 mg/rat when given by the same protocol of group A. In group B MR-356 also improved the survival rate (72 vs 39%, P < 0.05) only at 24 h, while other parameters failed to improve. The present results suggest that the PGE1 oligomer may play a beneficial role in bile-induced pancreatitis, probably through its proposed effects of stabilization of lysosomal membranes, maintenance of microcirculation and inhibition of protease in the pancreas.
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PMID:Protective effects of a prostaglandin E1 oligomer on taurocholate-induced rat pancreatitis. 148 88

This study was performed to assess the effects of misoprostol, a synthetic prostaglandin E1 analog, on cerulein-induced pancreatitis. Per group of 10 each, male Wistar rats received either cerulein (2.5 micrograms/kg/h subcutaneously), cerulein and misoprostol (500 micrograms/kg intraperitoneally at 0 and 4 h), or saline. Rats were killed 6 h after the first injection. Misoprostol treatment significantly reduced interstitial edema and acinar cell lesions induced by hyperstimulation. Pancreatic amylase and chymotrypsin contents were increased by cerulein and returned towards control levels in the misoprostol-treated group. The lysosomal volume density and the pancreatic beta-D-glucuronidase activity were significantly increased after hyperstimulation. The two parameters were significantly reduced by misoprostol. A protective effect of misoprostol against lesions induced by cerulein hyperstimulation would be a consequence of a lysosomal stabilizating effect.
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PMID:Protective effect of misoprostol, a synthetic prostaglandin E1 analog, on cerulein-induced acute pancreatitis in rats. 169 Apr 20

This study was performed to assess the effects of misoprostol (M), a synthetic prostaglandin E1 analog, on experimental pancreatitis in rat. Pancreatitis was induced by ligation of the main pancreatic duct of 3-month-old male Wistar rats. Pancreatic lesions were observed at 6, 12, 24, 48, and 96 h after pancreatic duct ligation (PDL). A time of 48 h was chosen to evaluate M treatment. M was injected intraperitoneally (500 micrograms/kg every 4 h) between time 0 and 48 h after PDL. Stereological analysis was performed on light and electron microscopy. Total pancreatic amylase and chymotrypsin concentrations were determined. Four groups of five rats were studied: sham operated (SO), M without PDL (PG), duct ligation without M (DL), and duct ligation with M (DLPG). Edema, dedifferentiation of pancreatic acinar cells, and heterogeneous distribution of zymogen granule diameters observed after PDL were significantly decreased by M in the DLPG group. Enzyme concentrations were also decreased by M in the DLPG group. Enzyme concentrations were also decreased by M both in normal (PG) and duct ligated rats (DL). M has protective effects against pancreatic lesions induced by PDL. In this model, the protective effect of M may be due to a blockade of the autodigestive secretions of the pancreatic acinar cells.
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PMID:Protective effect of misoprostol, a synthetic prostaglandin E1 analog, on experimental pancreatitis induced by pancreatic duct ligation in rat. 247 2

Prostaglandin E1 (PGE1) was tested for cytoprotective activity against the development of experimental acute pancreatitis in the rat induced by the closed duodenal loop technique. Sham-operated, untreated and PGE1-treated pancreatic rats were investigated. All rats received an initial bolus of 3 ml 5% dextrose in normal saline (D5NS) via jugular catheter 30 min prior to surgery, and a continuous subcutaneous infusion of 35 ml D5NS over 24 h. Each treated rat received 10 micrograms/kg PGE1 in the initial bolus and a maintenance dosage of 10 micrograms/kg/h via the infusate. Serum amylase rose significantly in all pancreatic rats with no significant difference between treated and untreated. Pancreatic edema was more pronounced in PGE1-treated than in untreated rats. The ischemic and autolytic damage to acinar cells and vascular endothelial cells typical of untreated pancreatitis was delayed by PGE1. Mortality rates were unaffected by PGE1.
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PMID:Prostaglandin E1 treatment in experimental acute pancreatitis in the rat. 620 76

Alcohol has at least two actions on essential fatty acid (EFA) and Prostaglandin (PG) metabolism. It enhances the conversion of dihomogammalinolenic acid (DGLA) to PGE1 but it blocks the activity of the delta-6-desaturase, an enzyme necessary for replenishment of DGLA stores from dietary precursors. The acute effect of ethanol is therefore an increased production of PGE1 but chronic consumption will lead to depletion of DGLA and PGE1. Withdrawal from alcohol will lead to a precipitous fall in PGE1. PGE1 is known to have profound effects on the nervous system and behaviour. Patients with mania produce more PGE1 than normal while those with depression make less. Alcoholics may drink to maintain a normal PGE1 level, something which will require more and more ethanol as DGLA is depleted. In both animals and humans PGE1 or its precursor, gamma-linolenic acid (GLA) have been shown to attenuate the acute withdrawal syndrome. PGE1 injections prevent the development of fatty liver in alcohol-treated animals. Defective EFA and PGE1 metabolism are known to lead to increased fibrosis, reproductive failure, cardiomyopathy, cardiovascular disorders, gastritis and pancreatitis and could therefore be the basis for these disorders in alcoholics. A PGE1 deficiency could also be responsible for the fetal alcohol syndrome. Three other agents are known to produce constellations of fetal defects very similar to those found in the alcohol syndrome. These other factors are dihphenylhydantoin, lithium, and a deficiency of zinc. These three factors and excessive alcohol consumption all lead to PGE1 deficiency by different routes. If this concept is correct, the key to the management of alcoholism and its medical complications lies in the provision of GLA or DGLA, fatty acids which by-pass the alcohol blocked step and which are unfortunately unlikely to be present in any normal diet. Unlike many concepts of alcoholism and alcohol damage, the EFA/PGE1 idea is very readily testable and already has considerable experimental support.
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PMID:A biochemical basis for alcoholism and alcohol-induced damage including the fetal alcohol syndrome and cirrhosis: interference with essential fatty acid and prostaglandin metabolism. 625 73

Changes in endogenous pancreas production of prostaglandins D2, F2 alpha, E2, and E1 in early stages of acute necrotizing pancreatitis induced by intraductal administration of 3.5% sodium taurocholate have been determined by radioimmunoassay of chromatographically purified tissue extracts. For this purpose 18 male Wistar rats were randomized in three groups: control, pancreatitis, and pancreatitis plus indomethacin. Pancreas tissue samples were obtained 5 min after pancreatitis induction. In the pancreatitis-induced group, prostaglandins D2, F2 alpha, and E2 show significantly increased tissue levels relative to the controls whereas prostaglandin E1 remains unmodified. These results suggest a role for series 2 prostaglandins in the earlier stages of pancreatitis.
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PMID:Prostaglandin D2, F2 alpha, E2, and E1 in early phase of experimental acute necrohemorrhagic pancreatitis in rats. 750 66

Infusion of a supramaximally stimulating dose of the pancreatic secretagogue caerulein (10 micrograms.kg-1.h-1) for 4 h induces interstitial edematous acute pancreatitis in rats. This model of acute pancreatitis is associated with evidence of acute lung injury, including sequestered neutrophils within the pulmonary microvasculature, increased microvascular permeability, and interstitial pulmonary edema. Infusion of prostaglandin E1 (PGE1; 50 ng.kg-1.min-1) along with caerulein does not alter the severity of secretagogue-induced pancreatitis, but it does reduce the severity of pancreatitis-associated acute lung injury. The rise in lung weight, lung water content, and pulmonary microvascular permeability and the sequestration of neutrophils within the pulmonary microvasculature that accompany secretagogue-induced pancreatitis are all reduced by infusion of PGE1. Infusion of PGE1 does not interfere with polymorphonuclear neutrophil sequestration in the pancreas or reduce the enhanced expression of CD11b/c receptors on circulating neutrophils. Our observations indicate that PGE1 reduces the severity of pancreatitis-associated acute lung injury by preventing neutrophil sequestration within the lung. We speculate that PGE1 interferes with neutrophil sequestration by dilating pulmonary vasculature, increasing pulmonary flow rate, and reducing neutrophil-endothelial cell interaction and attachment.
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PMID:Protective effects of prostaglandin E1 on acute lung injury of caerulein-induced acute pancreatitis in rats. 903 72

The pathophysiology of acute pancreatitis accompanied by chronic liver injury, and the therapeutic efficacy of prostaglandin (PG)E1 were studied experimentally in rats. Chronic liver injury was produced by subcutaneous administration of CCl4. Acute pancreatitis was induced by the closed duodenal loop (CDL) method, immediately after which PGE1 (60 ng/kg/min) was infused intravenously via the jugular vein. Serum levels of amylase, alpha2-macroglobulin-trypsin complex (alpha2M-TRY), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were determined before and at 3 and 6 h after the onset of acute pancreatitis. Rats without administration of CCl4 served as controls. Serum amylase levels were lower in the liver injury (LI) group than in the normal liver (NL) group at 3 and 6 h. PGE1 had no effect on amylase levels in either group. Serum alpha2M-TRY levels were similar in the two groups at 3 h, but significantly higher in LI than in NL at 6 h. PGE1 tended to decrease alpha2M-TRY levels only in LI. Serum CRP levels were significantly more elevated in LI than in NL at 0, 3, and 6 h. PGE1 decreased CRP levels only in LI. Serum TNF-alpha concentrations were higher in LI, especially at 6 h. PGE1 reduced TNF-alpha levels in LI. Pancreatitis severity scores were significantly higher in LI. PGE1 significantly decreased the severity scores only in LI. Fat necrosis scores were significantly lower in LI. Histologically, interstitial edema was much more prominent in NL than in LI, whereas interstitial hemorrhage was more severe in LI at 3 and 6 h. PGE1 lessened the hemorrhage in LI. The extent of both vacuolization and necrosis of acinar cells was similar for both groups and tended to be improved by PGE1. It is concluded that acute pancreatitis becomes much more serious in the presence of chronic liver injury, and that PGE1 can ameliorate the exacerbated lesions, probably by improvements in blood flow through the pancreatic tissue.
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PMID:Exacerbation of acute pancreatitis in the presence of chronic liver injury in rats, with special reference to therapeutic efficacy of prostaglandin E1. 1043 68

A 56-year-old female, who had been suffering from heart failure and diabetes mellitus, underwent posterior instrumentation in the prone position and anterior interbody fusion in the right lateral decubitus position for pyogenic spondylitis between the fourth and fifth lumbar spine under general and epidural anesthesia. We induced hypotensive anesthesia by using continuous infusion of dopamine, prostaglandin E1 and nitroglycerin in order to prevent heart failure and reduce the blood loss. After the operation, the patient complained of upper abdominal pain, nausea and vomiting. We found high levels of serum amylase and other pancreatic enzymes. The massive gas of small intestine was pooled in abdominal X-P, and the pancreatic head was slightly swollen in abdominal CT and US. Therefore we came to the diagnosis of postoperative acute pancreatitis. We administered a single bolus intravenous infusion of ulinastatine and continuous venous infusion of gabexate mesilate. As the serum amylase level gradually decreased, the patient improved. We suspect that postoperative pancreatitis was due to invasive anesthetic and surgical stress on the patient who had had pancreatitis in the preoperative period.
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PMID:[A case of acute pancreatitis that occurred after an operation of the lumbar spine]. 1088 49


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