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)

Indomethacin given orally or intramuscularly before or shortly after induction of acute sodium-taurocholate or olive-oil-induced pancreatitis in rats reduced the lethality. Neither the enzyme content of serum, ascites, and pancreatic tissue nor the damage to the organ itself were changed under the influence of indomethacin. Thus a modification of systemic effects of acute pancreatitis may be responsible for the beneficial effect of indomethacin.
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PMID:Indomethacin treatment of acute experimental pancreatitis in the rat. 70 58

We created acute pancreatitis in cats by instilling ethanol (20 ml of a 40% solution) into the stomach and then perfusing activated pancreatic enzymes through the main pancreatic duct. Edematous pancreatitis developed within 24 h as the enzymes leaked out of the duct into the surrounding pancreatic parenchyma. We tested the effects of a number of agents on the amelioration of the severity of the pancreatic inflammation. Cimetidine (an H2 receptor blocker) and Benadryl (an H1 receptor blocker) given in combination decreased the incidence of pancreatic hemorrhage but not the overall degree of inflammation. Indomethacin (a cyclooxygenase inhibitor) had a similar effect. Terbutaline (a beta-agonist) given alone decreased the overall degree of inflammation, including the incidence of hemorrhage. All of the drugs given together were no more effective than terbutaline alone. The combination was effective even when given up to 12 h after the onset of pancreatitis.
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PMID:Treatment of acute alcoholic pancreatitis in cats. 223 68

Acute edematous pancreatitis was produced in rats by subcutaneous administration of caerulein. Pancreas weight, pancreas histology and plasma amylase were used as endpoints to quantitate the severity of the syndrome. A caerulein dose of 10 micrograms/kg.hour produced the most severe pancreatitis, whereas at 5 micrograms/kg.hour the values were half-maximal. The pancreatic lesions were characterized by edema, formation of cytoplasmic vacuoles, leukocytic infiltration, necrosis, and with time (12-hour caerulein infusion) dilated acini. Cholecystokinin octapeptide also produced pancreatitis when given at ten times the dose required for caerulein (50 micrograms/kg.hour instead of 5 micrograms/kg.hour). Carbachol did not induce pancreatitis. Two prostaglandins, 16,16-dimethyl prostaglandin E2 injected subcutaneously and prostaglandin E2 infused subcutaneously, dose dependently prevented caerulein-induced pancreatitis (pancreatic edema, leukocytic infiltration, and necrosis) and reduced the number and size of intracellular vacuoles. The ED50 were 15 to 25 micrograms/kg for 16,16-dimethyl prostaglandin E2 and 90 micrograms/kg.hour for prostaglandin E2. Neither prostaglandin, given at doses inhibiting the development of pancreatitis, prevented the retardation of gastric emptying caused by caerulein, a finding suggesting that the prostaglandins may act specifically on the effect of caerulein on the pancreas but not on caerulein receptors in gastric smooth muscle. Indomethacin, an inhibitor of prostaglandin synthesis, and methscopolamine bromide, an anticholinergic agent, had no effect on caerulein-induced pancreatitis. We concluded that prostaglandins of the E type prevent the development of caerulein-induced pancreatitis. The mechanism by which prostaglandins protect the pancreas may involve stabilization of lysosomes within the acinar cells and inhibition of intracellular activation of pancreatic digestive enzymes.
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PMID:Prevention by prostaglandins of caerulein-induced pancreatitis in rats. 246 59

The effects of indomethacin administration on hemodynamics were investigated in canine acute hemorrhagic pancreatitis (AHP). Thirteen mongrel dogs were randomly divided into a fluid treatment group, an indomethacin prophylaxis group (IMP), and an indomethacin therapy (IM) group. Indomethacin (5 mg/kg) was administered as a bolus dosage 30 min before the induction of AHP in the IMP group. In the IM group, indomethacin was also given as a bolus (5 mg/kg) in 5 min starting 30 min after the induction of AHP. AHP was induced with a mixture of trypsin and sodium taurocholate infused into the pancreatic duct. Hemodynamics were monitored during the 4.5 h of surveillance time. Heart rate did not change significantly between the groups. Indomethacin prophylaxis maintained mean arterial pressure at a significantly higher level (P less than 0.05) and prevented the initial fall in blood pressure when compared to the fluid treatment or IM group. Indomethacin increased cardiac output (P less than 0.05) in the IM group, but did not differ significantly in the IMP group in comparison with the fluid treatment group. In conclusion, the inhibition of the initial fall in blood pressure by indomethacin in AHP suggests prostaglandins to play a role in hemodynamic changes and pancreatic shock to be "septic" as evaluated by hemodynamic changes.
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PMID:Indomethacin in canine acute hemorrhagic pancreatitis. 335 85

The possible role of thromboxane A2 (TXA2) in acute necrotizing pancreatitis (ANP) was investigated in rats. After ANP was induced by injecting sodium taurocholate (5% w/v) into the pancreatic duct, the thromboxane B2 (TXB2) levels in plasma increased significantly. The effects of indomethacin, a general blocker of prostaglandin synthesis, on survival time and on plasma TXB2 levels were compared with those of dazoxiben, a more specific blocker of TXA2 synthesis, and Flunarizine, a calcium entry blocker known to inhibit the effects of TXA2. In a test group without any treatment, all animals died within 30 h of ANP induction. Although TXB2 levels were lowered by the administration of indomethacin, dazoxiben, and Flunarizine, survival times were not significantly altered. Indomethacin pretreatment had no beneficial effect, whereas 30% and 40% of the animals survived for 36 h after treatment with Flunarizine and dazoxiben, respectively. The results of the present study indicate that inhibition of TXA2 synthesis alone does not dramatically alter survival time. However, a potential role for other arachidonate metabolites in ANP cannot be ruled out by this study.
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PMID:Raised plasma thromboxane B2 levels in experimental acute necrotizing pancreatitis in rats. The effects of flunarizine, dazoxiben, and indomethacin. 336 91

Phospholipase-A2 has been suggested as having a role in the pathophysiology of acute pancreatitis. The inhibition of phospholipase-A2 was studied in vitro using 17 pharmacological agents in the search for a specific therapy for acute pancreatitis. The inhibitory effect was tested using an isotopic assay system with 2-palmitoyl-(1-14C)-labelled dipalmitoyl phosphatidylcholine as a substrate and 10 microliters of serum from patients with acute necrotizing pancreatitis as an enzyme source. Among all agents tested, anti-inflammatory drugs inhibited enzyme activity most significantly: indomethacin (9.0 x 10(-3) mol l-1) decreased the phospholipase-A2 activity to one- tenth. The weak inhibitory effect could also be demonstrated using a lower concentration of 2 x 10(-5) mol l-1, which can be achieved after intravenous administration of 50 mg of this drug. The other drugs inhibited the enzyme activity at concentrations higher than those achieved after intravenous injections in clinical use. Diclofenac (3.1 x 10(-2) mol l-1) reduced the phospholipase-A2 activity by 93%, ketoprofen (2.0 x 10(-2) mol l-1) or chlorpromazine (1.4 x 10(-2) mol l-1) by 90%, tobramycin (1.7 x 10(-2) mol l-1) by 84%, doxycycline (9.0 x 10(-3) mol l-1) by 61%, dexamethasone (1.7 x 10(-3) mol l-1) by 62%, methylprednisolone (3.8 x 10(-2) mol l-1) by 50%, and pindolol (1.0 x 10(-4) mol l-1) by 59%. A weak inhibition of phospholipase-A2 activity was demonstrated by betamethasone, bupivacaine, digoxin, hydrocortisone, lidocaine, metoprolol, propranolol, and vancomycin. Indomethacin proved the most potent of the tested agents in inhibiting phospholipase-A2 activity in serum from patients with acute pancreatitis and should be further studied in vivo.
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PMID:Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. 927 65