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)

Two "in vivo" models of inflammation have been used to investigate the role of phospholipases A2 (PLA2) in inflammation. These models are casein-induced peritonitis in the rat and zymosan-induced peritonitis in the mouse. The extracellular PLA2 activities from peritoneal lavage fluid in these two models are similar: they are calcium dependent and have broad neutral pH optima. However, the relationship between extracellular PLA2 activity and cell influx in these models are not identical. In zymosan peritonitis, PLA2 activity preceded peak cell influx, reaching a maximum within 15 min after zymosan injection, while cell influx peaked by 8 hr. In casein-induced peritonitis, the PLA2 activity peaked at 24 hr, while cell influx continued through 48 hr. The origins of the PLA2 activities in both models remain unclear; one potential source is the plasma. Understanding the role of extracellular PLA2 activity in "in vivo" models, and investigating specific inhibitors in these models may aid in our understanding of the role of extracellular PLA2 in diseases such as rheumatoid arthritis, endotoxin shock and pancreatitis.
 ...
PMID:Extracellular phospholipase A2 activity in two in vivo models of inflammation. 212 42

The increasing application of ultrasonography in biliary tract disease had led to more frequent recognition of an old disorder--"biliary sludge." Sludge is detected on ultrasound as low-amplitude echoes without acoustic shadowing. It layers in the most dependent part of the gallbladder and shifts with positioning. Particulate matter in bile, such as cholesterol monohydrate crystals, has been shown to be echogenic. Agglomeration of these crystals in biles with high mucus content accounts for the layering and the characteristic appearance of the movement of sludge with alteration in patient position. Within the gallbladder, the stability of the vesicular form of cholesterol and protein-lipid interactions are important determinants of cholesterol precipitation. In mixed and pigment gallstones, the equilibrium between ionized and unionized calcium and the hydrolysis of conjugated bilirubin are also important factors. Although the risk factors contributing to the formation of gallbladder sludge have not been critically examined, it is now known that in some instances sludge can produce biliary pain and can be associated with acalculous cholecystitis, recurrent pancreatitis and, ultimately, the formation of gallstones. A better appreciation of the pathogenesis of sludge formation can help in the understanding of the genesis of gallstones and also perhaps in understanding other documented but poorly understood biliary and pancreatic disorders.
 ...
PMID:Pathogenesis of biliary sludge. 221 Jun 50

The effectiveness of continuous arterial infusion of protease inhibitor on acute experimental pancreatitis was investigated. Acute hemorrhagic pancreatitis was induced by closed duodenal loop obstruction using mongrel dogs. The obstruction was released at 16 hr, and dogs were divided into three groups; Group I: non-treated control, Group II: nafamostat mesilate (FUT-175) was admitted intravenously (5 micrograms/kg/min), Group III: FUT-175 was admitted via celiac artery. At 24 hr, the concentration of FUT-175 in the pancreatic tissues in group II and III were 905 and 4453 ng/g, respectively. The trypsin like activities in the pancreatic tissues in group I, II and III were 2.1, 1.4 and 0.7 nmol/min/mg protein, and the extent of necrosis of pancreatic parenchyma in each group were 49.5, 25.6 and 12.4%, respectively. Serum calcium, amylase and lipase levels were significantly improved in group III. These results suggest that continuous arterial infusion of protease inhibitor markedly decreases the extent of pancreatic necrosis in severe acute pancreatitis.
 ...
PMID:[Effect of continuous arterial infusion of protease inhibitor on experimental acute pancreatitis induced by closed duodenal loop obstruction]. 221 68

The nonhydrolyzable guanyl nucleotide GTP gamma S stimulated phosphoinositidase C activity in two preparations obtained from mouse pancreatic acini labeled with myo[2-3H]inositol: a cell-free membrane fraction and intact electropermeabilized acini. This action was dose-dependent, was shared by other nonhydrolyzable guanyl nucleotides such as GMP-phencyclidine hydrochloride and GMP-PMP, as well as by fluoride, and was calcium-independent. Contrarily, no effect was observed even at doses of GTP gamma S as high as 10 microM when the same protocol was repeated on identical acinar preparations from mice fed a choline-deficient, ethionine-supplemented diet. This regimen is known to uncouple secretagogue-receptor occupancy from inositol 1,4,5-trisphosphate generation in pancreatic acinar cells and lead to necrotizing hemorrhagic pancreatitis. These data lead us to conclude that the ethionine-induced inactivation of guanyl nucleotide-dependent pancreatic phosphoinositidase C in pancreatic acinar cells is not the result of either a decrease in GTP level or a decrease in GTP availability. These findings further confirm previous work from this laboratory, which has shown that the biochemical lesion induced by this diet occurs after the agonist-receptor binding step. The diet-induced lesion could be either at the level of the G-protein that couples the enzyme with the receptor or at the level of the phospholipase itself.
 ...
PMID:Effects of a choline-deficient ethionine-supplemented diet on phospholipase C activity in mouse pancreatic acinar cell membranes and in electropermeabilized mouse pancreatic acini. 233 59

To determine the role of magnesium deficiency in the pathogenesis of hypocalcemia in acute pancreatitis, we measured magnesium levels in serum and in peripheral blood mononuclear cells in 29 patients with acute pancreatitis, 14 of whom had hypocalcemia and 15 of whom had normal calcium levels. Only six patients had overt hypomagnesemia (serum magnesium less than 0.70 mmol per liter [1.7 mg per dl]). The mean serum magnesium concentration in hypocalcemic patients was not significantly lower than in normocalcemic patients, but the mononuclear cell magnesium content in hypocalcemic patients with pancreatitis was significantly lower than in normocalcemic patients with pancreatitis (P less than .01). The serum magnesium level did not correlate with that of serum calcium or the mononuclear cell magnesium content, but the latter did significantly correlate with the serum calcium concentration (r = .81, P less than .001). Most patients with hypocalcemia had a low intracellular magnesium content. Three normomagnesemic, hypocalcemic patients with alcoholic pancreatitis also underwent low-dose parenteral magnesium tolerance testing and showed increased retention of the magnesium load. We conclude that patients with acute pancreatitis and hypocalcemia commonly have magnesium deficiency despite normal serum magnesium concentrations. Magnesium deficiency may play a significant role in the pathogenesis of hypocalcemia in patients with acute pancreatitis.
 ...
PMID:Low intracellular magnesium in patients with acute pancreatitis and hypocalcemia. 240 29

Serum calcium changes in severe pancreatitis were studied in 23 dogs. Twelve dogs underwent duodenotomy and served as controls. Pancreatitis was induced in the other 11 by autologous bile injection (1 ml/kg) into the pancreatic duct. Serum amylase, total calcium, ionized calcium, albumin, magnesium, chloride, phosphorous, parathyroid hormone (PTH), and calcitonin were measured at 0, 1/2, 1, 3, 6, 24, 48, and 72 hours after duodenotomy or bile injection. Serum amylase levels became significantly elevated in all dogs with pancreatitis at 30 minutes (p less than 0.01) and remained so throughout the entire experiment. Total calcium levels dropped significantly 30 minutes after pancreatitis was induced from 10.0 +/- 0.3 mg/dl compared with 8.8 +/- 0.4 mg/dl in control dogs (p less than 0.05) and remained statistically lower for as long as 1 hour. Ionized calcium levels were significantly lower than were those of control dogs at 1/2, 1, 3, and 6 hours (p less than 0.05). Serum magnesium and chloride levels showed no significant changes between both groups. The only significant difference in phosphorus values was at 6 hours when they were higher in dogs with pancreatitis than in controls (6.2 +/- 0.3 mg/dl versus 4.8 +/- 0.4 mg/dl; p less than 0.05). Serum albumin levels remained unchanged throughout the study except for 48 hours when they were significantly lower in animals with pancreatitis (p less than 0.02). PTH levels were significantly greater in dogs with pancreatitis than in controls at 1, 3, 6, and 24 hours (p less than 0.05). There was no significant difference in calcitonin levels between both groups. Ionized calcium is a more reliable indicator of calcium fluxes in acute experimental pancreatitis since it remains depressed longer than total serum calcium. The time course of PTH elevation indicates a reaction to hypocalcemia, and failure of PTH secretion is not the cause of hypocalcemia in pancreatitis. This study does not support elevation of calcitonin as a cause of hypocalcemia in acute pancreatitis.
 ...
PMID:Serum calcium metabolism in acute experimental pancreatitis. 241 69

Elevated values of pancreatic-type amylase activity in serum were found in 59% of patients with liver cirrhosis not complicated with renal failure, in 67% of patients with chronic renal failure not complicated with hepatopathy and in 95% of patients with chronic renal failure complicated with hepatopathy. In all the three groups, a significant positive correlation was found between the pancreatic-type amylase and intestinal isoenzyme of serum alkaline phosphatase which is an asialoglycoprotein. However, in pancreatitis a prevalence of an increase in pancreatic-type amylase with respect to intestinal alkaline phosphatase was found. A multivariate analysis showed that in chronic renal failure not complicated with hepatopathy, and in chronic renal failure complicated with chronic liver disease, the changes in calcium homeostasis and also the liver disorder, respectively, contribute significantly to the above-normal values for pancreatic-type amylase.
 ...
PMID:Role of secondary hyperparathyroidism and liver function in hyperamylasemia in chronic renal failure. 241 93

Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet rapidly develop acute hemorrhagic pancreatitis. We have observed that pancreatic acini prepared from these mice are unable to secrete amylase in response to addition of the cholinergic agonist carbachol, although they retain the ability to secrete amylase in response to the Ca2+ ionophore A23187. The CDE diet does not alter the binding characteristics (Kd or the maximal number of binding sites) for muscarinic cholinergic receptors as tested using the antagonist [3H]N-methylscopolamine nor the competition for this binding by carbachol. Addition of carbachol to acini prepared from mice fed the CDE diet does not result in as marked an increase in cytosolic free Ca2+ levels as that noted in control samples (evaluated using quin2 fluorescence). These observations indicate that the CDE diet interferes with stimulus-secretion coupling in mouse pancreatic acini at a step subsequent to hormone-receptor binding and prior to Ca2+ release. This conclusion is confirmed by our finding that the hormone-stimulated generation of [3H]inositol phosphates (inositol trisphosphate, inositol bisphosphate, and inositol monophosphate) from acini labeled with [3H]myoinositol is markedly reduced in acini prepared from mice fed the CDE diet. This reduction is not due to a decrease in phosphatidylinositol-4,5-bisphosphate. This communication represents the first report of a system in which a blockade of inositol phosphate generation can be related to a physiologic defect and pathologic lesion.
 ...
PMID:Diminished agonist-stimulated inositol trisphosphate generation blocks stimulus-secretion coupling in mouse pancreatic acini during diet-induced experimental pancreatitis. 242 12

Pancreatitis was induced in the opossum by occluding the common bile duct above or below the entrance of the pancreatic duct. The common channel theory was tested by evaluating the effect of preligation of the pancreatic duct to prevent the reflux of bile after ligation of the distal common duct. The severity of the disease was determined by histologic grading of the degree of pancreatic tissue necrosis. Serum amylase, lipase, and calcium were determined. Concomitant obstruction of the biliary and pancreatic ducts produced severe necrotizing pancreatitis whether or not bile reflux was present. Pancreatic ductal obstruction alone was associated with acinar atrophy and mild interstitial pancreatitis. Biliary obstruction alone above the entrance of the pancreatic duct resulted in marked hyperemia of the gland but without histologic evidence of pancreatic inflammation. A positive bacterial culture of the pancreas was obtained in only four of 36 opossums in a distribution to suggest random contamination. There was an inverse correlation between calcium levels and the degree of tissue necrosis. This study demonstrates that biliary obstruction rather than bile reflux into the pancreas is a requisite for the pathogenesis of severe biliary pancreatitis in this model.
 ...
PMID:The role of biliary obstruction in the pathogenesis of acute pancreatitis in the opossum. 242 9

The incidence and possible etiologic factors of acute pancreatitis and hyperamylasemia were statistically evaluated in renal transplant recipients. Two hundred twenty-four patients were randomized in a prospective trial of cyclosporine and antilymphoblast azathioprine immunosuppressive regimens. They had a median follow-up of 20 months. Pancreatitis developed in 8 patients and hyperamyl asemia developed in 20 patients. There were no statistical relationships between the incidences of pancreatitis and hyperamylasemia and the immunosuppressive drugs or viral infections. However, pancreatitis developed in 11 percent of the transplant patients with repeatedly elevated serum calcium levels (37 patients, p less than 0.01) and hyperamylasemia developed in 19 percent (p less than 0.025). Other etiologic factors, such as gallstones, alcoholism, and corticosteroids, played a minor role in this patient population. These results suggest that hypercalcemia is a major etiologic factor for pancreatitis in renal transplant recipients.
 ...
PMID:Hypercalcemia associated with pancreatitis and hyperamylasemia in renal transplant recipients. Data from the Minnesota randomized trial of cyclosporine versus antilymphoblast azathioprine. 244 14


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