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)

Hemorrhagic pancreatitis was induced in cats by perfusing pancreatic enzymes through a pancreatic duct after the administration of intragastric ethanol. Dimethyl prostaglandin E2 was administered concurrently. In the first study, dopamine's antiinflammatory effect on the pancreas was determined in the presence of haloperidol, propranolol, or both. Next, dopamine's effects on blood flow in the normal and inflamed pancreas were compared using a hydrogen gas-clearance technique. In the final study, the effect of dopamine on fluorescein isothiocyanate-labeled dextran leakage from the pancreatic duct to portal venous blood was investigated. It was found that blockade of either dopamine or beta-adrenergic receptors reduced, and blockade of both receptors completely eliminated, the antiinflammatory effect. Dopamine had no effect on pancreatic blood flow in normal cats. In pancreatitis, although dopamine transiently reduced blood flow, after an hour flow had returned to normal. Dopamine reversed the leakage of fluorescein isothiocyanate-labeled dextran from the pancreatic duct caused by ethanol and by ethanol and prostaglandin E2. It was concluded that dopamine ameliorated pancreatitis by reducing pancreatic ductal and/or microvascular permeability rather than by altering pancreatic blood flow. The antiinflammatory effect was mediated by both dopamine and beta-adrenergic receptors.
 ...
PMID:The antiinflammatory effect of dopamine in alcoholic hemorrhagic pancreatitis in cats. Studies on the receptors and mechanisms of action. 165 48

The present work reviews the evidence for an involvement of free radicals in the pathophysiology of chronic pancreatitis and the potential of treatment with antioxidant and scavenger substances. Preliminary results indicate that exposure of isolated pancreatic acinar cells to a reaction mixture containing hypoxanthine, xanthine oxidase, and chelated iron causes cell damage and death probably due to generation of superoxide anion and hydrogen peroxide. It still needs to be analyzed which scavengers and antioxidants are able to ameliorate the damage due to oxidant stress in cell models. Such knowledge from cellular studies might help to plan therapeutical trials to evaluate potentially effective antioxidants and scavengers in the experimental animal and in patients with pancreatitis. As yet there are no published studies about the role of free radicals in animal models of chronic pancreatitis. This fact is probably due to the shortcomings of the animal models available. Recent studies presented evidence that activation of oxygen-derived free radicals occurs in patients with chronic pancreatitis. There is also some evidence that the dietary intake of antioxidants may be reduced in patients with chronic pancreatitis. It was suggested that such reduction of antioxidant defenses in the face of an increased demand due to heightened induction of P450 activities may facilitate lipid peroxidation. However, as yet, there is no direct evidence that a reduction of dietary antioxidants with a simultaneous increase in P450 activity is the primary mechanism which initiates chronic pancreatitis without contribution of other factors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Involvement of free radicals in the pathophysiology of chronic pancreatitis: potential of treatment with antioxidant and scavenger substances. 179 74

Acute edematous and necrotic pancreatitis have been induced in dogs with retrogradely intraductal injections of 5% hydrogen peroxide solution and sunflower-oil. The process of disease could be followed daily by a zipper sutured into the abdominal wound. In this manner the temporal changes of markers of oxygen-derived free radicals (concentrations of malondialdehyde and reduced glutathione of the excised pancreas tissue and abdominal exudate, as well as the superoxide dismutase content of the tissue) could be controlled. Light microscopic analysis was also done. In edematous pancreatitis reversible membrane lesions, in the necrotic form the irreversible damage of membranes and cells could be seen. The results obtained suggest the role of oxygen-derived free radicals in experimental acute pancreatitis.
 ...
PMID:Oxygen-derived free radical reactions in experimental acute pancreatitis of the dog. 209 70

Bentiromide test (BT) has been recently approved in the United States for screening patients with chronic pancreatitis for exocrine insufficiency. A few reports have suggested that the rice flour breath hydrogen test (RFBHT)--i.e., breath hydrogen analysis after rice flour ingestion--may also be useful in diagnosing exocrine pancreatic insufficiency. We conducted this study to compare the diagnostic value of these two tests in chronic alcoholic (n = 14) and nutritional or tropical (n = 6) pancreatitis. False-positive results were not noted with either of these two tests in 12 healthy volunteers. BT was positive in 28.6% of patients with chronic alcoholic pancreatitis and in 16.7% of patients with tropical pancreatitis. In comparison, RFBHT was almost twice as sensitive as BT in detecting insufficiency in patients with alcoholic pancreatitis (50 vs. 28.6%) and four times as sensitive in patients with tropical pancreatitis (66.7 vs. 16.7%). Only one patient in our study had a positive BT but a negative RFBHT. We recommend RFBHT as a simple, safe, and inexpensive test in screening patients for exocrine pancreatic insufficiency.
 ...
PMID:Comparison of bentiromide test and rice flour breath hydrogen test in the detection of exocrine pancreatic insufficiency. 349 92

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.
 ...
PMID:The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis. 620 83

A woman ingested 400 ml of leather tanning solution containing 48 g of basic chromium sulphate (CrOHSO4). This substance forms hydrogen ions and trivalent chromium when it reacts with tissue proteins. The patient died of cardiogenic shock, complicated by pancreatitis and gut mucosal necrosis and haemorrhage. There are no reported cases of toxicity due to oral ingestion of trivalent chromium. Toxicity of hexavalent and trivalent chromium is discussed and suggestions made for management of future cases.
 ...
PMID:Death by tanning--a case of fatal basic chromium sulphate poisoning. 820 Oct 96

The hydrogen clearance technique (HCT) was employed for measurements of local pancreatic blood flow (PBF) in dogs, opossums, and rats under normal conditions and in opossums during biliary pancreatitis. Local PBF (ml/min/100 g) in dogs was 57.6 +/- 10.4, in opossums 60.6 +/- 9.5, and in rats 144.7 +/- 23.4, under resting conditions. Regional distribution of local PBF in dogs showed no statistical differences. Technical aspects of the HCT were described in detail. Under physiological conditions parenchymal trauma following electrode implantation was negligible in nearly all cases. More than 95% of registered clearance curves were monoexponential and showed excellent reproducibility of PBF values in repeated measurements (percentage deviation < or = 6.7). Five days after initiating biliary pancreatitis by common channel ligation in opossums local PBF was 72.1 +/- 14.7 after implantation of new electrodes. Chronically implanted electrodes, however, recorded only 39.7 +/- 15.8, due to massive fibro-proliferative alterations around the implanted electrode tips. We therefore conclude that the HCT as described is a useful tool for measuring local PBF in acute experimental settings only. Biliary pancreatitis in our model causes no significant alterations of PBF after 5 days.
 ...
PMID:Use of the hydrogen clearance technique for measurements of pancreatic blood flow. 841 90

In order to understand the mechanism of acute renal failure frequently observed in severe acute pancreatitis, renal microcirculation and renal hemodynamics were investigated during experimental acute pancreatitis in dogs induced by autologous bile and trypsin mixture into the pancreatic duct. Renal tissue blood flow (hydrogen gas clearance method), renal arterial blood flow, and cardiac output (transonic blood flow meter) were each measured for 5 h after induction of pancreatitis. The effect on renal hemodynamics of a new synthesized protease inhibitor--E-3123; 4-(2-succinimidoethylthio)phenyl-4-quanidinobenzoate methane sulfonate--intravenously infused at the rate of 3 mg/kg/h was also investigated. The mean blood pressure and pulse pressure decreased after induction of pancreatitis. Renal microcirculation and renal artery blood flow decreased during the experiment. However, in dogs with treated by E-3123, renal microcirculation was preserved during the first hour of the experiment and decreased gradually afterward, but it was significantly higher than that of the dogs without E-3123 during 3-5 h. The mean blood pressure and pulse pressure were preserved nearly at preoperative levels during the experimental period. We concluded that renal microcirculation decreased concomitantly with a deterioration of acute pancreatitis, and that the new pancreatic protease inhibitor E-3123 may have some beneficial effect to improve renal hemodynamics in the early period of acute pancreatitis.
 ...
PMID:Renal microcirculation in experimental acute pancreatitis of dogs. 844 33

Transforming growth factor-beta1 (TGF-beta1) is a multifunctional polypeptide that is related to the progression of chronic pancreatitis. However, the mechanism of beta-cell damage by TGF-beta1 is unknown. Treatment with TGF-beta1 enhanced internucleosomal DNA cleavage caused by exogenous hydrogen peroxide in a hamster pancreatic beta-cell line (HIT). TGF-beta1 also induced protein oxidation, assessed by measuring carbonyl groups in proteins, and was involved in reactions that lead to lipid peroxidation. This eventually destructs membrane lipids and forms malondialdehyde. We have investigated its effects on two major antioxidative enzymes, catalase and glutathione peroxidase (GPx). TGF-beta1 suppressed mRNA expression as well as reduced the activities of catalase and GPx. The decrease in the catalase and GPx activities in TGF-beta1-treated cells resulted in an increase in intracellular peroxides as judged by flow cytometric analysis using a peroxide-sensitive dye, 2',7'-dichlorofluorescin diacetate. These data suggest that the augmented production of reactive oxygen species by TGF-beta1 through suppression of antioxidative enzymes may cause cellular damage and consequent apoptosis and induce pancreatitis or diabetes.
 ...
PMID:TGF-beta1 triggers oxidative modifications and enhances apoptosis in HIT cells through accumulation of reactive oxygen species by suppression of catalase and glutathione peroxidase. 903 40

Polyamines are required for optimal growth and function of cells. Regulation of their cellular homeostasis is therefore tightly controlled. The key regulatory enzyme for polyamine catabolism is the spermidine/spermine N(1)-acetyltransferase (SSAT). Depletion of cellular polyamines has been associated with inhibition of growth and programmed cell death. To investigate the physiological function SSAT, we generated a transgenic rat line overexpressing the SSAT gene under the control of the inducible mouse metallothionein I promoter. Administration of zinc resulted in a marked induction of pancreatic SSAT, overaccumulation of putrescine, and appearance of N(1)-acetylspermidine with extensive depletion of spermidine and spermine in transgenic animals. The activation of pancreatic polyamine catabolism resulted in acute pancreatitis. In nontransgenic animals, an equal dose of zinc did not affect pancreatic polyamine pools, nor did it induce pancreatitis. Acetylated polyamines, products of the SSAT-catalyzed reaction, are metabolized further by the polyamine oxidase (PAO) generating hydrogen peroxide, which might cause or contribute to the pancreatic inflammatory process. Administration of specific PAO inhibitor, MDL72527 [N(1),N(2)-bis(2,3-butadienyl)-1,4-butanediamine], however, did not affect the histological score of the pancreatitis. Induction of SSAT by the polyamine analogue N(1),N(11)-diethylnorspermine reduced pancreatic polyamines levels only moderately and without signs of organ inflammation. In contrast, the combination of N(1), N(11)-diethylnorspermine with MDL72527 dramatically activated SSAT, causing profound depletion of pancreatic polyamines and acute pancreatitis. These results demonstrate that acute induction of SSAT leads to pancreatic inflammation, suggesting that sufficient pools of higher polyamine levels are essential to maintain pancreatic integrity. This inflammatory process is independent of the production of hydrogen peroxide by PAO.
 ...
PMID:Activation of polyamine catabolism in transgenic rats induces acute pancreatitis. 1088 May 65


1 2 3 Next >>