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)

Previous studies using the isolated ex vivo perfused canine pancreatitis preparation showed that during a 4-hour perfusion pancreatitis (edema, weight gain, hyperamylasemia) can be induced by four different stimuli. The stimuli include the intra-arterial infusion of oleic acid (FFA), a 2-hour period of ischemia before perfusion (ISCH), partial obstruction of the pancreatic duct with secretin stimulation (POSS), and the intra-arterial infusion of cerulein at supramaximal doses (CER). In the present study, changes in high-energy phosphate metabolism, as determined by nuclear magnetic resonance spectroscopy, and changes in cellular structure, determined by light and electron microscopy, were documented for all four models of acute pancreatitis. The control preparations remained stable for the 4-hour perfusion period, with no decrease in adenosine triphosphate (ATP) levels. In the FFA preparations, ATP decreased to 36% of baseline levels during the 4-hour perfusion (p less than 0.001). In the ISCH preparations, ATP decreased to undetectable levels during the 2-hour period of ischemia, but recovered rapidly and remained at baseline levels during the perfusion. ATP levels remained stable in the remaining two models of pancreatitis (POSS, CER). Microscopy demonstrated that the initial injury was located chiefly in the capillaries (swollen endothelium, intravascular thrombi) in the FFA and ISCH preparations. In the POSS and CER preparations, capillary changes were minimal and the injury was located chiefly in the acinar cells (swollen endoplasmic reticulum, zymogen granule depletion, vacuolization). The POSS preparations also showed striking dilation of centroacinar lumens reflecting duct obstruction. In additional studies it was shown that the ATP decline in the FFA preparations could be significantly reduced by pretreatment with free radical scavengers. The morphologic changes could be reduced by free radical scavengers in the FFA and ISCH preparations. Any amelioration of morphologic injury in the POSS preparations was obscured by dilatation of centroacinar lumens in both treated and untreated groups. The morphologic changes in the CER preparations were reduced by treatment with a cholecystokinin inhibitor.
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PMID:Changes in high-energy phosphate metabolism and cell morphology in four models of acute experimental pancreatitis. 200 16

Because the severity of acute pancreatitis is difficult to assess in the early stage, analyses were made of the diagnostic specificity and sensitivity of computed tomography (CT), C-reactive protein (CRP), serum phospholipase A2 and other laboratory parameters. In a series of 88 patients with clinically suspected severe acute pancreatitis, statistically significant differences were found between mild and severe disease in regard to CRP (97.1 vs. 265.7 mg/l), contrast enhancement of the pancreas at CT (45.3 vs. 22.7 Hounsfield units) and phospholipase A2 activity (5.3 vs. 11.2 nmol FFA/ml min). No significant intergroup difference was found in number of prognostic signs (1.7 vs. 4.1) or in extrapancreatic scores at CT (4.4 vs. 6.4). The sensitivity/specificity of different methods in severe pancreatitis were as follows: Prognostic signs 77.5/75%, CRP (greater than 140 mg/l) 100/81%, phospholipase A2 (greater than 11 nmol FFA/ml min) 42/100%, extrapancreatic score at CT (greater than 4) 100/29%, and contrast enhancement of the pancreas (less than 30 HU) 66/100%. Amylase determination was nonspecific (2-4%). The outcome in acute pancreatitis was most accurately predictable with CT or CRP.
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PMID:Early assessment of acute pancreatitis. A comparative study of computed tomography and laboratory tests. 246 76

In order to study the changes of lipid metabolism in acute pancreatitis, the following experiments were performed in monogrel dogs. Bile-induced pancreatitis (severe type) and collagenase-induced pancreatitis (mild type) were prepared, and changes of FFA, TG, IRI and IRG were determined for one week. In addition, IVFTT and PHLA were determined at 24th hour, on the 3rd day and 7th day. A rise of FFA was observed during the first 24 hours, which was considered the lypolytic stage. On the 3rd day TG reached the maximal level, while K values in IVFTT and PHLA showed the lowest levels. The above results suggest that the elimination mechanism of TG was impaired on the 3rd day. Changes of FFA, TG, IRI and IRG showed marked differences between the two groups. Therefore it is thought that lipid metabolism in acute pancreatitis is regulated by balance of endogenous pancreatic hormones.
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PMID:[Lipid metabolism in experimental acute pancreatitis]. 329 13

The present study examines the value of C-reactive protein (CRP) determinations in the assessment of the severity of acute pancreatitis and the correlation of CRP with serum phospholipase A2 activity and the clinical status. Fifty three patients with acute pancreatitis were studied; 17 with haemorrhagic pancreatitis and 36 with a mild form of the disease. S-phospholipase A2 activity increased significantly (p less than 0.05) in patients with fatal pancreatitis but not in those with mild disease. Phospholipase A2 concentrations were below 10 nmol FFA/ml min in mild, while they rose to 20-40 nmol FFA/ml min in haemorrhagic pancreatitis. In fatal cases very high (up to 50-60 nmol FFA/ml min) serum phospholipase A2 concentrations were recorded. The increase in CRP was greater in the patients with severe pancreatitis. One day after admission mean CRP was 280 mg/l in patients with haemorrhagic and 45 mg/l in those with the mild pancreatitis (p less than 0.001). High CRP values also correlated with the prognostic signs indicative of severe pancreatitis. CRP and S-phospholipase A2 determinations are valuable in the early assessment of the severity of acute pancreatitis, but the CRP assay is much easier to include in hospital routine.
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PMID:C-reactive protein (CRP) and serum phospholipase A2 in the assessment of the severity of acute pancreatitis. 362 21

Oxygen-derived free radicals mediate an important step in the initiation of experimental acute pancreatitis in the ex vivo perfused canine pancreas model. In other organ systems, circulating leukocytes may serve as one source of oxygen-derived free radical production. The current experiments were designed to evaluate the role of circulating leukocytes in the generation of injury in this model. Four experimental groups of animals were studied: group I consisted of controls (n = 6); group II had white blood cell (WBC) depletion (n = 4) in which the recirculating whole blood perfusate was depleted of 98% of its circulating leukocytes; group III had oleic acid infusion (FFA) alone (n = 9), which induced pancreatitis; group IV had WBC depletion and FFA (n = 6), in which oleic acid was infused after depletion of the circulating leukocytes in the perfusate. During the 4-hour perfusion period, the pancreatic preparations were monitored hourly for the development of edema, weight gain, and release of alpha-amylase into the perfusate. Animals in groups I and group II manifested no gross edema, gained minimal weight, and did not manifest hyperamylasemia. Leukocyte depletion alone had no effect. In group IV animals marked edema, significant weight gain, and hyperamylasemia developed to the same extent as in group III animals. These results demonstrate that circulating leukocytes are not essential to the development of pancreatitis in this model and suggest that another source of oxygen-derived free radicals mediates this injury.
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PMID:The role of leukocytes in the production of oxygen-derived free radicals in acute experimental pancreatitis. 382 56

Oxygen-derived free radicals play an important role in the pathogenesis of experimental acute pancreatitis in the isolated perfused canine pancreas. We have previously found that pretreatment with allopurinol inhibits xanthine oxidase--apparently the primary source of free radical generation in this model--and prevents the initial development of pancreatitis. In these experiments, we evaluated whether allopurinol administered after the onset of pancreatitis would arrest the progression of the disease process. Edema formation, weight gain, and the release of amylase activity into the perfusate in the ex vivo perfused canine pancreas model were monitored during a 4-hour perfusion period. There were six experimental groups: Group I (control) received no treatment, group II (allopurinol alone) received only allopurinol (100 mg) at the start of perfusion, and groups III through VI were each given an infusion of 0.3 ml of oleic acid (FFA) over a 1-hour period to initiate acute pancreatitis. Group III (FFA alone) received no other treatment. In group IV (pretreatment with allopurinol), group V (concurrent treatment with allopurinol), and group VI (posttreatment with allopurinol), allopurinol (100 mg) was administered 1 hour before, concurrent with, or at the end of the FFA infusion, respectively. Pretreatment with allopurinol prevented edema formation, markedly attenuated weight gain, and the release of amylase caused by the FFA infusion. Administration of allopurinol concurrent with the FFA infusion provided only partial protection, whereas posttreatment with allopurinol failed to arrest the progression of the injury process. Therefore, the use of allopurinol to inhibit oxygen-derived free radical production from xanthine oxidase prevented the development of acute pancreatitis in this model; however, treatment with allopurinol after initiation of the disease process failed to arrest the progression of acute pancreatitis.
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PMID:Temporal efficacy of allopurinol during the induction of pancreatitis in the ex vivo perfused canine pancreas. 382 61

Acute pancreatitis may be initiated in the ex vivo, perfused canine pancreas preparation by a variety of stimuli. These include oleic acid infusion (FFA), partial duct obstruction with secretin stimulation (POSS), and a 2-hour period of ischemia (ISCH). In each model, pancreatitis is characterized by weight gain, edema, and hyperamylasemia. Oxygen-derived free radicals such as superoxide, hydrogen peroxide, and the hydroxyl radical are highly reactive toxic substances that are normally produced in small amounts during oxidative metabolism. Ordinarily, these substances are detoxified by endogenous intracellular enzymes called free radical scavengers (FRS), such as superoxide dismutase (SOD) and catalase (CAT). These studies were undertaken to evaluate the possible role of oxygen-derived free radicals in the initiation of acute pancreatitis in the isolated canine model. All preparations were perfused for 4 hours with autologous blood. Controls (N = 6): these glands remained normal in appearance, gained minimal weight (6 +/- 1 g), and serum amylase remained normal (less than 1000 u/dl). FFA pancreatitis, FFA alone (N = 6): these glands became edematous, gained weight (113.5 +/- 27.0 g), and developed hyperamylasemia (2087 +/- 387 u/dl). FFA + FRS (N = 6), SOD (50 mg) and CAT (50 mg) were added to the perfusate at time zero: these glands became only minimally edematous, gained less weight (31.8 +/- 10.1 g, p less than 0.05), and amylase remained normal (p less than 0.05). POSS pancreatitis, POSS alone (N = 8): these glands became edematous, gained weight (38.6 +/- 4.6 g), and developed marked hyperamylasemia (9522 +/- 3226 u/dl). POSS + FRS (N = 6): these glands did not develop edema, gained less weight (15.1 +/- 2.6 g, p less than 0.05), and serum amylase only increased to 1815 +/- 343 u/dl, (p less than 0.05). ISCH pancreatitis, ISCH alone (N = 6): these glands became edematous, gained weight (75.8 +/- 25 g), and developed hyperamylasemia (1679 +/- 439 u/dl). ISCH + FRS (N = 6): these glands did not develop edema, gained only 18.3 +/- 9.0 g (p less than 0.005), and serum amylase remained normal (p less than 0.05). These studies demonstrate that, in this canine preparation, acute pancreatitis is significantly ameliorated by oxygen-free radical scavengers. Since this was true whether the pancreatitis was produced by FFA infusion, POSS, or ischemia, it suggests that oxygen-derived free radicals may mediate a common essential step in the pathogenesis of all forms of pancreatitis.
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PMID:The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis. 620 83

Four models of acute pancreatitis have been previously developed that use the ex vivo perfused isolated canine pancreas preparation. The four models include the intraarterial infusion of oleic acid (FFA) that mimics hyperlipemic pancreatitis, partial obstruction of the pancreatic duct with secretin stimulation (POSS) that mimics gallstone pancreatitis, a 2-hour period of ischemia before perfusion (ISCH 2) that mimics shock pancreatitis, and the infusion of cerulein at supramaximal stimulatory doses (CER), which lacks an obvious clinical counterpart. In the FFA, POSS, and ISCH 2 pancreatitis, but not in the CER pancreatitis, toxic oxygen metabolites, generated by the enzyme xanthine oxidase (XO), have been shown to be important mediators in the early pathogenesis. Ordinarily XO primarily occurs as xanthine dehydrogenase (XD) but can be converted to XO, which is the form that generates toxic oxygen metabolites. This conversion of XD to XO may take place either reversibly by way of sulfhydryl group oxidation or irreversibly by means of proteolytic cleavage of XD. This study was undertaken to investigate the mechanism of conversion of XD to XO in the FFA-, POSS-, and ISCH 2-induced pancreatitis models. CER pancreatitis was studied for comparison. After 4 hours of perfusion, pancreatitis was manifest by edema, weight gain, and hyperamylasemia in all four models. Dithiothreitol, a sulfhydryl group protector, ameliorated the weight gain in the FFA (40 +/- 14 gm to 18 +/- 13 gm; p < 0.05), POSS (28 +/- 10 gm to 9 +/- 3 gm; p < 0.05), and ISCH 2 pancreatitis (30 +/- 13 gm to 15 +/- 3 gm; p < 0.05), and ameliorated the hyperamylasemia in the POSS pancreatitis (12,062 +/- 4304 units/dl to 5877 +/- 2659 units/dl; p < 0.05). The CER pancreatitis was not ameliorated with dithiothreitol. A serine protease inhibitor of low molecular weight, phenylmethylsulfonyl fluoride, ameliorated only the CER pancreatitis (weight gain from 28 +/- 10 gm to 17 +/- 10 gm, p < 0.05; amylase activity from 38,116 +/- 6491 units/dl to 23,372 +/- 11,654 units/dl, p < 0.05), and not the FFA, POSS, or ISCH 2 pancreatitis. We conclude that in the three models of pancreatitis (FFA, POSS, and ISCH 2) that are mediated by toxic oxygen metabolites, XD is converted to XO reversibly by way of sulfhydryl group oxidation rather than irreversibly by way of proteolysis. In the CER pancreatitis, where XO does not play a role in the pathogenesis, proteolytic enzymes may be important mediators in the injury.
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PMID:The mechanism of conversion of xanthine dehydrogenase to xanthine oxidase in acute pancreatitis in the canine isolated pancreas preparation. 841 95