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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats infused with a supramaximally stimulating dose of the cholecystokinin-pancreozymin analogue caerulein develop acute interstitial pancreatitis (M. Lampel and H.F. Kern. Virchows Arch. A 373: 97-117, 1977). We have studied the early (30-180 min) morphological changes in pancreatic acinar cells induced by infusing caerulein (2.5 micrograms X kg-1 X h-1). The techniques of thin-section electron microscopy, freeze fracture, and enzyme and immunocytochemistry were employed. Shortly (30 min) after the onset of caerulein infusion, large vacuoles appeared in the Golgi area. After longer periods of infusion, these vacuoles further enlarged (probably by fusion with other such vacuoles as well as autophagic vacuoles) and became more widely distributed in the cytoplasm. These large vacuoles were found to be acid phosphatase positive and to be labeled by antibodies directed against digestive zymogens as well as the lysosomal enzyme cathepsin D. These observations indicate that the large vacuoles contain both digestive zymogens and lysosomal hydrolases. During caerulein infusion, morphological evidence of exocytosis at the luminal plasmalemma was reduced or absent, and evidence of basolateral exocytosis was not noted. These studies suggest that secretagogue hyperstimulation with caerulein interferes with the processes involved in condensing vacuole maturation, which normally lead to the separation of digestive zymogens and lysosomal hydrolases. As a result, both types of enzymes remain within the same compartment. This may lead to the intracellular activation of digestive enzymes by lysosomal hydrolases and be an important step in the development of acute pancreatitis.
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PMID:Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: early morphological changes during development of experimental pancreatitis. 672 Aug 95

To investigate the relationship between the duodenal outputs of calcium and diseases of the pancreas, we measured calcium secretion into the duodenum (during saline perfusion and after stimulation with an intravenous infusion of cholecystokinin (CCK) or secretin) in healthy controls, patients with chronic alcoholic or idiopathic pancreatitis, and patients with pancreatic cancer. The effects of acute and chronic hypercalcaemia and previous cholecystectomy were also studied. Our results indicate a characteristic increase in duodenal calcium outputs in response to CCK in chronic pancreatitis which is unaffected by the level of serum calcium, aetiology of the pancreatitis, previous cholecystectomy, and the presence or absence of radiological pancreatic calcifications. Although unproven, indirect observations support a pancreatic source for the increased calcium secretion. As we measured the outputs of calcium into the duodenum, previously described increases in calcium concentration are not merely a reflection of reduced volume secretion in chronic pancreatitis. Duodenal calcium outputs were significantly reduced in patients with cancer of the pancreas.
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PMID:Duodenal calcium outputs in health and pancreatic disease. 742 25

Stimulation of the exocrine pancreas with cholecystokinin analogues leads to a variety of intraacinar processes, many coupled to energy consumption. It was hypothesized that extensive ATP depletion could play a role in the pathophysiology of acute pancreatitis, especially in the hyperstimulation (cerulein) model. Mice received seven intraperitoneal injections of cerulein at hourly intervals, at doses ranging from physiological (0.1 micrograms/kg) to pharmacological (50 micrograms/kg). A single dose of cerulein induced a 28-33% decrease in ATP, whereas a complete course of injections led to a nadir as low as 45% of the control value. The overall pattern of ATP tissue content during the observed time course was surprisingly similar in all four groups and statistically not different at any time point. Until 12 h, ATP levels in all groups remained below the control value. In contrast, serum amylase and light microscopy reflected a degree of pancreatitis in a close dose-response pattern to the administered cerulein dose. These findings suggest that ATP depletion--although probably facilitating acinar damage--does not seem to play a causal or primary role in the pathophysiology of acute pancreatitis.
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PMID:Energy metabolism in mouse pancreas in response to different dosages of a CCK analogue. 747 70

We studied the effect on the rat pancreas of a choline-deficient diet supplemented with ethionine administered over different time periods. The study was carried out in several groups of male Wistar rats weighing 300 gm and fed for 60, 104, 195, 250, and 336 hours with a choline-deficient diet supplemented with ethionine (CDE). Analysis of pure exocrine pancreatic secretion in animals fed the CDE for 60 hours revealed a decrease in total protein, amylase, and trypsin as compared with animals fed a standard diet. After cholecystokinin stimulation, a gradual decrease in secretion was observed as the duration of the CDE was increased, such that after 336 hours no response to cholecystokinin was found, indicating the lack of pancreatic functionality. Analysis of pancreas preparations by light microscopy showed the existence of infiltration, edema, and hemorrhagic foci after 60 hours of CDE administration. As the duration of the treatment increased, pancreatic morphology deteriorated, with the appearance of vacuolization and foci of necrosis at 195 hours. This deterioration became more pronounced after 250 to 336 hours, progressing to a considerable degree of hemorrhage and necrosis of the acinar tissue. These results clearly confirm the existence of acute necrotizing and hemorrhagic pancreatitis in rats fed a CDE for 250 to 336 hours.
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PMID:Acute necrotizing pancreatitis induced by a CDE diet in the rat: a morphologic and functional study. 751 92

1. We have assessed the role of platelet-activating factor in caerulein-induced acute pancreatitis (four subcutaneous injections of caerulein at a dose of 20 micrograms/kg) by measuring platelet-activating factor levels in portal blood, pancreatic tissue and peritoneal exudate in rats with and without pancreatitis. 2. We have also observed the effect of the platelet-activating factor antagonist, BN-52021, on the hyperamylasaemia and exocrine pancreatic secretion impairment associated with pancreatitis. 3. In rats with pancreatitis the basal pancreatic flow rate was increased (1.63 +/- 0.41 versus 0.25 +/- 0.03 microliters/min). Total protein output was similar in both untreated (5.98 +/- 1.93 micrograms/min) and caerulein-injected (6.5 +/- 2.0 micrograms/min) animals. Amylase output was lower in rats with pancreatitis (19.6 +/- 4.8 mu-units/min) than in controls (39.4 +/- 16.6 mu-units/min). 4. Caerulein-treated animals had significantly higher serum amylase levels than untreated animals. BN-52021 significantly reduced the caerulein-induced hyperamylasaemia. 5. Portal blood platelet-activating factor levels increased in rats with pancreatitis and in rats infused with cholecystokinin. Rats injected with caerulein and BN-52021 had portal blood levels of platelet-activating factor that were lower than those with pancreatitis. 6. Morphological derangements associated with pancreatitis (inflammatory infiltration and cell vacuolization) were also markedly reduced in BN-52021-treated animals. 7. The results of this study suggest that platelet-activating factor is involved in the development of caerulein-induced acute pancreatitis in rats.
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PMID:Platelet-activating factor mediates pancreatic function derangement in caerulein-induced pancreatitis in rats. 752 Mar 81

Hyperamylasemia of pancreatic origin has been noted in patients with severe head injury without abdominal trauma or evidence of pancreatitis. Thirty-eight patients with intracranial bleeding of various types were evaluated for elevated pancreatic amylase and lipase enzymes without associated pancreatitis. Twenty-five patients had elevated serum lipase; 17 of 25 also had elevated amylase without pancreatitis. Most lipase elevations occurred earlier than those of amylase. Six clinical variables--mannitol, ceftriaxone, nimodipine, steroids, Glasgow Coma Score, and total parenteral and enteral hyperalimentation--were evaluated to determine relationship to the enzyme elevations. A significant relationship exists between patients not treated with steroids and elevated lipase and amylase enzyme activities. Multivariate analysis revealed a significant interaction between lipase elevation and decreasing Glasgow Coma Score, indicative of increasing severity of intracranial bleeding. Proposed causes of enzyme elevations in intracranial bleeding include vagal stimulation, altered modulation of the central control of pancreatic enzyme release, and release of cholecystokinin from the brain. Physician awareness of the association of intracranial bleeding with the elevation of amylase and lipase without pancreatitis can save the patient needless cost and manipulation.
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PMID:Significance of elevated pancreatic enzymes in intracranial bleeding. 752 51

Creation of a closed duodenal loop produced edematous acute pancreatitis within 6 h and hemorrhagic acute pancreatitis within 12 h in male Sprague-Dawley rats. The pancreatitis thus established tended to improve after releasing the loop. We investigated the effect of a new cholecystokinin receptor antagonist, KSG 504, on the healing process in edematous and hemorrhagic acute pancreatitis after releasing the loop. Serum amylase and lipase levels in the control group decreased gradually after releasing the loop, but the reductions were not significant. In both the group treated with KSG 504 intravenously and the group treated subcutaneously, serum amylase and lipase levels decreased markedly upon release of the loop in edematous acute pancreatitis. Furthermore, the histologic changes in edematous acute pancreatitis improved more rapidly than in the control group. However, no such biochemical or histologic evidence of improvement was observed in hemorrhagic acute pancreatitis. The new cholecystokinin receptor antagonist, KSG 504, displayed a therapeutic effect in edematous acute pancreatitis but not in hemorrhagic acute pancreatitis. These findings suggest that endogenous cholecystokinin release induced by the closed duodenal loop may have a contributory role in the development of edematous acute pancreatitis but not of hemorrhagic acute pancreatitis.
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PMID:Effect of a new cholecystokinin receptor antagonist (KSG 504) on the early stage of the healing process in acute pancreatitis induced in rats by the closed duodenal loop technique. 752 65

Previous studies have suggested that the metabolism of methyl groups is an important factor in the function of the exocrine pancreas. Ethionine, an inhibitor of cellular methylation reactions, produces hemorrhagic pancreatitis when administered to mice fed a choline-deficient diet. Glycine N-methyltransferase, an enzyme which regulates the ratio of S-adenosylmethionine to S-adenosylhomocysteine, is particularly abundant in the exocrine pancreas. Since de novo synthesis of methyl groups requires the participation of folate coenzymes, we investigated the effect of folate deficiency on pancreatic exocrine function. Rats were fed an amino acid-defined folate-deficient diet or the same diet supplemented with folate ad libitum. A third group received the folate supplemented diet pair-fed to the deficient group. After 3 and 5 wk, pancreatic amylase secretion was measured in perfused duodenal segments of anesthetized animals before and after cholecystokinin injection. Pancreatic secretion was significantly reduced in the deficient group compared with the pair-fed control group after 5 wk. These results indicate that severe folate deficiency impairs pancreatic exocrine function.
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PMID:Folate deficiency inhibits pancreatic amylase secretion in rats. 752 61

In necrotizing pancreatitis a high interleukin-6 (IL-6) serum level has been proposed as a prognostic criterium. However, literature does not report any information about the role of IL-6 in the function of pancreatic acinar cells. Cholecystokinin, gastrin binding, amylase release and intracellular calcium measurement were performed on a rat pancreatoma cell line, AR4-2J, which has been recognized as a useful tool for studies on the long-term regulation of pancreatic acinar cells. The addition of IL-6 (400 pM) for 48hrs to the AR4-2J cells induced no change in the binding affinities but there was a 2 fold increase in the binding capacity of cholecytokinin (CCKA R) and gastrin (CCKB R) receptors. Although IL-6 treatment did not change directly the secretory capacity and did not activate the intracellular calcium mobilization of AR4-2J, it indirectly increased the sensitivity of the cells to the stimulation of amylase release and the intracellular calcium mobilization by cholecystokinin and gastrin. It is most likely this effect was due to the IL-6-induced increase in the numbers of CCKA R and CCKB R. Therefore this report suggests that the cytokine IL-6 acts on the CCK regulation of pancreatic enzyme secretion.
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PMID:Interleukin-6 regulation of CCK/gastrin receptors and amylase secretion in a rat pancreatic acinar cell line (AR4-2J). 753 49

Recent studies have demonstrated that cholecystokinin (CCK) receptor antagonists not only reduce the severity of pancreatitis but also inhibit pancreatic regeneration after pancreatitis. This study was undertaken, therefore, to examine the effects of the CCK receptor antagonist loxiglumide on the exocrine pancreas when given after an episode of acute pancreatitis that was induced in rats by a 4-h subcutaneous infusion of 20 micrograms/kg body weight/h cerulein. Biochemical changes and secretory function in response to 100 ng/kg body weight cerulein were determined after a 6-day treatment with saline, loxiglumide (50 mg/kg body weight), or CCK-8 (2.5 micrograms/kg body weight), which was given three times a day starting 24 h after the induction of acute pancreatitis. In the saline-treated rats, pancreatic enzyme contents and pancreatic juice and protein output were significantly low, whereas the pancreatic weight and protein and DNA contents were comparable to those of the controls without pancreatitis. Loxiglumide treatment, although significantly decreasing protein output, had no influence on pancreatic weight, protein and DNA contents, or pancreatic juice flow but increased the amylase and lipase contents compared to those of the saline-treated postpancreatitic rats. CCK-8 treatment also had no influence on pancreatic weight or protein and DNA contents but significantly increased the pancreatic enzyme contents and pancreatic juice and protein output compared to those of the saline-treated postpancreatitic rats. These results suggest that loxiglumide does not significantly inhibit the recovery of exocrine function but appears to accelerate the increase in pancreatic amylase and lipase contents even when given after an attack of acute pancreatitis.
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PMID:Effect of the cholecystokinin receptor antagonist loxiglumide on pancreatic exocrine function in rats after acute pancreatitis. 754 70


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