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)

Acute pancreatitis was experimentally produced in dogs to study the effect of the disease on glucose tolerance. The k value (glucose disappearance coefficient measured in percentage decrease of glucose/min) calculated from the high-dose intravenous glucose-tolerance test was used to evaluate the glucose tolerance of each dog. Thirty dogs were allotted to 3 groups of 10 dogs each as follows: group I--nonsurgical control dogs; group II--surgical control dogs; and group III--pancreatitis-affected dogs. To increase their susceptibility to diabetes, 50% partial pancreatectomies and ductal catheterizations were performed on group II and III dogs. Saline solution was infused into the ductal systems of group II dogs, and staphylococcal alphatoxin was infused into the ductal systems of group III dogs to produce pancreatitis. The results indicated that (1) high-dose intravenous glucose-tolerance test was an effective tool for determining decreased glucose tolerance in dogs; (2) glucose tolerance of group III dogs was markedly decreased compared with that of group I and II dogs; (3) staphylococcal alpha-toxin produced signs of moderately severe pancreatitis; and (4) 50% partial pancreatectomy and saline solution infusion produced clinical and clinicopathologic signs of mild pancreatitis. To determine if a simplified k value (calculated using 2 or 3 blood samples) could closely approximate the standard k value (calculated using 6 blood samples), simplified k values were derived from the 5- and 60-minute blood sample values. These values closely approximated the standard k values, indicating the simplified value may be used in the clinical situation. The standard k value, however, is preferred for investigative work.
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PMID:Effect of staphylococcal alpha-toxin pancreatitis on glucose tolerance in the dog. 94 22

Three hundred sixty Sprague-Dawley rats were allocated into four groups, according to different content of a 24-h i.v. infusion performed 1 h after intrabiliary injection of enterokinase/sodium taurocholate to induce acute pancreatitis (AP): (1) Saline; (2) 5 micrograms/kg/h nafamostat mesilate (FUT-175); (3) 10 micrograms/kg/h FUT-175; and (4) 25 micrograms/kg/h FUT-175. Peritoneal fluid was removed and exchanged with 1 mL 3.33 M fluorescein-isothiocyanate-conjugated (FITC) dextrans of 4000-40,000 Dalton. Serial blood samples were withdrawn and examined for FITC-dextrans, phospholipase A2 (PLA2), blood gases, amylase, and lipase. As compared to control (55%), FUT-175 brought about a lower (5 micrograms/kg/h: 25%) or no mortality (10 and 25 micrograms/kg/h), and a milder histological and biochemical evidence of AP. Untreated animals with PLA2 values over two times the standard deviation showed a respiratory distress. Further, unlike group 1, FUT-175 doses as low as 5 micrograms/kg prevented the increase in peritoneal permeability to small-size molecules (up to 20,000 Dalton). In a second experiment under the same drug protocol, 1000 U/mL of PLA2 and 2 mL of pancreatitis ascites were instilled ip. Peritoneal permeability to FITC-dextrans up to 30,000 Dalton and to PLA2 significantly increased in the saline group and in the 5 micrograms/kg FUT-175 group. However, 10 micrograms/kg and 25 micrograms/kg FUT-175 doses prevented such phenomenon. In conclusion, FUT-175 proves to be a potent antiprotease molecule with a biochemical activity also against PLA2 in vivo and prevents significant transperitoneal-blood access of pancreatic enzymes.
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PMID:Nafamostat mesilate on the course of acute pancreatitis. Protective effect on peritoneal permeability and relation with supervening pulmonary distress. 752 62

We investigated the concentration of immunoreactive pancreatic phospholipase A2 (pan-PLA2) and the catalytic activity of phospholipase A2 (CA-PLA2) in plasma, peritoneal fluid, and pancreas of rats in which acute hemorrhagic pancreatitis was induced by an intraductal injection of sodium taurocholate. The contribution of pancreas to the CA-PLA2 in plasma was studied by removing pancreatic PLA2 by absorbing plasma samples with a polyclonal antibody raised in a rabbit against rat pancreatic PLA2. Sodium taurocholate injected into the pancreatic duct produced hemorrhagic pancreatitis with necrosis and inflammatory cell invasion within 8 hr. Saline injection caused edematous pancreatitis, but sham operation did not alter pancreatic morphology from normal. The concentration of pan-PLA2 increased rapidly in plasma in all animals, but significantly more in sodium taurocholate-injected animals than in saline-injected or sham-operated animals. The level of CA-PLA2 in plasma increased in sodium taurocholate-injected animals only. There was no correlation between pan-PLA2 and CA-PLA2 values in plasma in sodium taurocholate-injected animals. The CA-PLA2 was marginally increased in pancreatic tissue of sodium taurocholate-injected animals compared to that of saline-injected and sham-operated animals at 8 hr. Treatment by the anti-pan-PLA2 antibody effectively removed pan-PLA2 from plasma and peritoneal fluid samples in sodium taurocholate-injected animals. The level of CA-PLA2 in plasma was similar before and after antibody treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phospholipase A2 in sodium taurocholate-induced experimental hemorrhagic pancreatitis in the rat. 763 43

To investigate the debated role of intracellular trypsinogen activation and its relation to lysosomal enzyme redistribution in the pathogenesis of acute pancreatitis, rats were infused with the cholecystokinin analog caerulein at 5 micrograms.kg-1.h-1 for intervals up to 3 h, and the changes were contrasted with those in animals receiving saline or 0.25 microgram.kg-1.h-1 caerulein. Saline or 0.25 microgram.kg-1.h-1 caerulein did not induce significant changes. In contrast, 5 micrograms.kg-1.h-1 caerulein caused significant hyperamylasemia and pancreatic edema within 30 min. Pancreatic content of trypsinogen activation peptide (TAP) increased continuously (significant within 15 min). TAP generation was predominantly located in the zymogen fraction during the first hour but expanded to other intracellular compartments thereafter. Cathepsin B activity in the zymogen compartment increased continuously throughout the experiments and correlated significantly with TAP generation in the same compartment. Total trypsinogen content increased to 143% with marked interstitial trypsinogen accumulation after 3 h. Supramaximal caerulein stimulation causes trypsinogen activation by 15 min that originates in the zymogen compartment and is associated with increasing cathepsin B activity in this subcellular compartment. However, a much larger pool of trypsinogen survives and accumulates in the extracellular space and may become critical in the evolution of necrotizing pancreatitis.
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PMID:Subcellular kinetics of early trypsinogen activation in acute rodent pancreatitis. 945 75

The pathological activation of zymogens within the pancreatic acinar cell plays a role in acute pancreatitis. To identify the processing site where activation occurs, antibodies to the trypsinogen activation peptide (TAP) were used in immunofluorescence studies using frozen sections from rat pancreas. Saline controls or animals receiving caerulein in amounts producing physiological levels of pancreatic stimulation demonstrated little or no TAP immunoreactivity. However, after caerulein hyperstimulation (5 micrograms. kg-1. h-1) for 30 min and the induction of pancreatitis, TAP immunoreactivity appeared in a vesicular, supranuclear compartment that demonstrated no overlap with zymogen granules. The number of vesicles and their size increased with time. After 60 min of hyperstimulation with caerulein, most of the TAP reactivity was localized within vacuoles >/=1 micrometer that demonstrated immunoreactivity for the granule membrane protein GRAMP-92, a marker for lysosomes and recycling endosomes. Pretreatment with the protease inhibitor FUT-175 blocked the appearance of TAP after hyperstimulation. These studies provide evidence that caerulein hyperstimulation stimulates trypsinogen processing to trypsin in distinct acinar cell compartments in a time-dependent manner.
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PMID:Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis. 981 30

Transcription factor nuclear factor-kappaB (NF-kappaB) is activated in cerulein pancreatitis and mediates cytokine expression. The role of transcription factor activation in other models of pancreatitis has not been established. Here we report upregulation of NF-kappaB and inflammatory molecules, and their correlation with local pancreatic injury, in a model of severe pancreatitis. Rats received intraductal infusion of taurocholate or saline, and the pancreatic head and tail were analyzed separately. NF-kappaB and activator protein-1 (AP-1) activation were assessed by gel shift assay, and mRNA expression of interleukin-6, tumor necrosis factor-alpha, KC, monocyte chemoattractant protein-1, and inducible nitric oxide synthase was assessed by semiquantitative RT-PCR. Morphological damage and trypsin activation were much greater in the pancreatic head than tail, in parallel with a stronger activation of NF-kappaB and cytokine mRNA. Saline infusion mildly affected these parameters. AP-1 was strongly activated in both pancreatic segments after either taurocholate or saline infusion. NF-kappaB inhibition with N-acetylcysteine ameliorated the local inflammatory response. Correlation between localized NF-kappaB activation, cytokine upregulation, and tissue damage suggests a key role for NF-kappaB in the development of the inflammatory response of acute pancreatitis.
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PMID:Localized pancreatic NF-kappaB activation and inflammatory response in taurocholate-induced pancreatitis. 1135 13