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)

Under conditions of physiological loading at feeding, histologically and radio-autographically (35S-methionine), granuloformation and protein metabolism have been studied in exocrinic pancreocytes in mature white rats under abundant injection of hydrocortisone (6 daily injections, 1 mg per 100 g of body mass). The procedure stimulates formation of zymogen granules, but intensity of the excretion remains unchanged. This results in overfilling the cell with the secretory product, considered as the base of the alterative changes, that in their turn could stimulate the development of the steroid pancreatitis.
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PMID:[Synthesis and discharge of secretions in the pancreas of the white rat in the presence of excessive hydrocortisone]. 395 4

We measured amino acid concentrations in plasma and skeletal muscle of three groups of patients with acute hemorrhagic pancreatitis: (a) patients without secondary organ lesions, (b) patients also suffering from kidney damage, and (c) patients in whom the pancreatitis was accompanied by sepsis and multiple organ failure. In all three groups, especially the third group, the amino acid concentrations in both plasma and muscle were below normal. Glutamine was only 14% of normal in muscle tissue of the third group. Onset of renal insufficiency was indicated by increasing values for 3-methylhistidine and cystathionine; multiple organ failure, by increased concentrations of methionine and phenylalanine in plasma. The low amino acid concentrations of patients with acute pancreatitis can be explained as a combined effect of semistarvation and hypercatabolism. Changes in the plasma concentrations of amino acids did not reflect necessarily the concentrations in muscle tissue.
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PMID:Amino acid concentrations in plasma and skeletal muscle of patients with acute hemorrhagic necrotizing pancreatitis. 401 35

Calcium antagonists may limit experimental tissue injury by membrane stabilization. We studied the effects of verapamil on pancreatic ultrastructure and zymogen extraction during diet-induced acute pancreatitis. Acute pancreatitis was induced in female Swiss-Webster mice by feeding a choline- and methionine-deficient diet (CD) supplemented with 1% ethionine (CDE). Varying doses of verapamil in normal saline were infused continuously at a rate of 0.5 microliter/hr for 96 hr through subcutaneously implanted osmotic pumps. The pancreata were examined blindly by light microscopy and by electron microscopy. Zymogen extracted from pancreatic tissue was measured and expressed per gram of protein. Mean histological scores, calculated according to a formula that incorporates the extent of necrosis, inflammation, acidophilia, and edema, were 14.1 +/- 4, 10.3 +/- 2, 9.9 +/- 4, 5.9 +/- 7, 12.5 +/- 4, and 12.7 +/- 4 for CDE-fed animals receiving 0, 0.14, 0.28, 0.56, 0.84, and 1.12 microM verapamil daily, respectively. Animals fed normal diet or CD had scores of 0 +/- 0. Histological scores were significantly lower in animals treated with 0.56 microns verapamil compared to animals who received no verapamil (p < 0.05) and was associated with reduced dissolution of the zymogen granule membrane on EM. Mean extracted trypsinogen and chymotrypsinogen content were reduced in the CD- and CDE-fed mice. The reduction in mean trypsinogen content reached statistical significance in CDE-fed mice treated with verapamil 0.56 microM daily. Mean chymotrypsinogen content was also significantly reduced CD-mice and in mice treated with 0.56 microns and 0.84 microM of verapamil daily. Increasing doses of verapamil protect against diet-induced pancreatitis in mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dose-dependent effect of continuous subcutaneous verapamil infusion on experimental acute pancreatitis in mice. 758 13

Chronic ethanol ingestion is a primary factor in the development of pancreatitis in humans. Alterations in both enzyme secretion and protein synthesis have been implicated as causative factors. We determined the effect of chronic ethanol feeding on the content and synthesis rates of digestive enzymes in dispersed acini from rats that were pair-fed isocaloric diets with or without ethanol for 3-6 months. Total protein content and synthesis were unchanged. The relative synthetic rates of individual digestive enzymes were analyzed using scanning laser densitometry of 1-D sodium dodecylsulfate (SDS) gels. The content of all measurable digestive enzymes except amylase increased in acini from ethanol-fed rats. Relative synthetic rates were examined in pancreatic acini labeled in vitro with [35S]methionine. Liquid scintillation counting of radiolabeled digestive enzymes extracted from gel slices revealed that amylase synthesis in ethanol-fed rats decreased 2.8-fold compared with controls whereas the synthetic rates of proelastase 1 and 2, chymotrypsinogen, and trypsinogen increased by 1.5-, 1.4-, 1.8-, and 1.6-fold, respectively. Total cellular RNA was extracted from control and ethanol-fed rats and subjected to Northern and dot blot analysis. Amylase mRNA decreased in ethanol-fed rats whereas chymotrypsinogen and trypsinogen mRNA content increased, indicating that the effect of ethanol on expression of these genes was regulated at a step prior to translation. Elastase mRNA content was not altered, suggesting that the increased synthesis of proelastase may be regulated posttranscriptionally.
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PMID:Effect of chronic ethanol feeding on digestive enzyme synthesis and mRNA content in rat pancreas. 789 55

The removal of amino acids during continuous renal replacement therapies induces clinical problems. Previous studies on animals have shown nephroprotective (glycine, alanine) or negative effects (lysine) on renal function in occurrence of acute renal failure. Disturbed metabolism in acute renal failure needs adequate parenteral nutrition. On the other hand, experience with continuous renal replacement therapies of metabolic crises in inborn errors of metabolism indicate a good control of disturbed amino acid metabolism. The aim of our study was to find amino acids, that might play an important role in the pathogenesis, prognosis and detection of acute renal failure and severe illness, so far only estimated by lactic acid. Thirty-three probes (serum and hemofiltrate) were taken from patients, suffering with acute renal failure caused by septic shock, severe pancreatitis and hepatorenal syndrome, one hour after the beginning of extracorporal circulation, the conditions of treatment were standardized. The material was deproteinized and studied by the amino acid analyzer LBK 4251 Apha Plus (Pharmacia, Stockholm, Sweden), while the lactic acid concentration was determined in a standard laboratory. Proline, glycine, alanine, methionine and histidine showed a close relationship to the lactic acid levels, but these amino acids were an essential part of parenteral nutrition. A statistical relationship was also established in (amino acids with amide groups) asparagine, glutamine, citrulline, cystathionine and phosphoethanolamine. The mean values of most of the amino acids were higher than normal, but standard deviations were increased. The presence of these amino acids in hemofiltrate and the good sieving coefficients could mean that the better prognosis of critically ill patients in continuous renal replacement therapies may also be due to continuous control of amino acid levels (especially with amide groups).
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PMID:Which amino-acids do serum and hemofiltrate of critically ill patients with acute renal failure contain? 925 6

The traditional ductal model for the development of chronic pancreatitis leaves many questions unanswered and it has not facilitated management. An alternate philosophy centres on the acinar cell as the site of mounting oxidant stress, usually as a result of steady exposure to xenobiotics that induce cytochrome P450 mono-oxygenases while depleting glutathione: ductal changes are regarded as secondary, disease-compounding manifestations of the oxidant environment. Within this framework each burst of oxidant stress jeopardises exocytosis, to trigger an attack of pancreatitis by interfering with the methionine-to-glutathione transsulphuration pathway, which interacts closely with ascorbate and selenium. The resulting diversion of free radical oxidation products into the pancreatic interstitium causes mast cells to degranulate, thereby provoking inflammation, the activation of nociceptive axon reflexes, and profibrotic interactions.
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PMID:A framework for the aetiogenesis of chronic pancreatitis. 983 31

The Manchester 'oxidant stress' hypothesis for the development of pancreatitis accommodates published information on both chronic pancreatitis and acute pancreatitis. Oxidant stress, mainly from reactive xenobiotic metabolites, is perceived as the pivotal pre-morbid problem in chronic pancreatitis and, by depleting glutathione, targets the exocytosis mechanism of the pancreatic acinar cell. Inhalation exposure to petrochemical products is identified as an independent risk factor in patients at Manchester Royal Infirmary, where some 50% of patients referred have non-alcoholic disease. This paper describes the development of antioxidant therapy, using supplements of methionine, vitamin C and selenium, and its validation in a placebo-controlled trial, followed by a retrospective cross-sectional study in 94 consecutive patients for an average of 30 months. Antioxidant therapy emerges as a safe and effective medical alternative to surgery for painful chronic pancreatitis.
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PMID:Chronic pancreatitis at Manchester, UK. Focus on antioxidant therapy. 983 34

Mice deficient in either or both mouse alpha2-macroglobulin (MAM) and murinoglobulin-1 (MUG1) were generated and proved phenotypically normal under standard conditions. Acute pancreatitis was induced with a diet deficient in choline and methionine, supplemented with ethionine. The mortality was less than 25% in wild-type mice, as opposed to at least 56% in knockout mice, and was highest (70%) in MAM-/- mice, with earliest onset at 2 days. Plasma amylase and lipase levels were increased, but pancreatic tissue appeared histologically variable in individual mice. The clinical symptoms were most severe in MAM-/- mice and, surprisingly, were not aggravated in the double knockout mice, suggesting that the lack of proteinase inhibition capacity was not the major problem. Therefore, we analyzed the expression of 21 different cytokines and polypeptide factors in the pancreas of all experimental groups of mice. Interleukin-1-receptor antagonist mRNA was consistently induced by the diet in the pancreas of MAM-/- mice, and transforming growth factor-beta, tumor necrosis factor-alpha, tumor necrosis factor-beta, beta-lymphotoxin, and interferon-gamma mRNA levels were also increased. The data demonstrate the important role of alpha2-macroglobulin (A2M) in acute pancreatitis as both a proteinase inhibitor and a cytokine carrier. Mice deficient in MAM and/or MUG thus offer new experimental models for defining in vivo the role of the macroglobulins in pancreatitis and in other normal and pathological processes.
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PMID:alpha2-macroglobulin- and murinoglobulin-1- deficient mice. A mouse model for acute pancreatitis. 1048 56

Pancreatic oedema occurs early in the development of acute pancreatitis, and the overall extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is released from sensory nerves, binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process termed neurogenic inflammation. We sought to determine the importance of neurogenic mechanisms in acute pancreatitis. Pancreatic plasma extravasation was measured using the intravascular tracers Evans blue and Monastral blue after administration of specific NK1-R agonists/antagonists in rats and NK1-R(+/+)/(-/-) mice. The effects of NK1-R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein-induced pancreatitis were characterized. In rats, both SP and the NK1-R selective agonist [Sar(9) Met(O(2))(11)]SP stimulated pancreatic plasma extravasation, and this response was blocked by the NK1-R antagonist CP 96,345. Selective agonists of the NK-2 or NK-3 receptors had no effect. In rats, cerulein stimulated pancreatic plasma extravasation and serum amylase. These responses were blocked by the NK1-R antagonist CP 96,345. In wildtype mice, SP induced plasma extravasation while SP had no effect in NK1-R knockout mice. In NK1-R knockout mice, the effects of cerulein on pancreatic plasma extravasation and hyperamylasemia were reduced by 60%, and pancreatic MPO by 75%, as compared to wildtype animals. Neurogenic mechanisms of inflammation are important in the development of inflammatory oedema in acute interstitial pancreatitis.
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PMID:Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice. 1082 77

Whole-blood free amino acids were measured in a control group made up of eight healthy women fasted for 12 h and also in eight patients with acute pancreatitis, five patients with acute cholecystitis and seven patients with acute appendicitis. Blood was withdrawn immediately on admission to hospital and again 3 d later following a controlled peripheral parenteral nutrition diet; this is with the exception of the appendicitis group. l-Cystathionine and l-methionine concentrations were significantly higher in pancreatitis and appendicitis patients when compared with controls. In the pancreatitis and cholecystitis patients, l-serine concentration was also significantly higher when compared with controls. The l-homocysteine concentration was significantly higher only in the appendicitis group when compared with the control group. l-Cystine concentration was unchanged in all the patients studied when compared with control subjects. The l-methionine : l-cystine ratio was significantly higher and the l-glutamine : l-cystine ratio was significantly lower in all the patients when compared with controls. The blood S-amino acid pattern reflects an impairment in liver transsulfuration pathway during acute abdominal processes. This work supports the idea that the l-methionine : l-cystine and l-glutamine : l-cystine ratios can be taken as good markers to evaluate the S-amino acid metabolism and suggests the importance of using N-acetylcysteine as a required nutrient in these situations.
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PMID:Blood sulfur-amino acid concentration reflects an impairment of liver transsulfuration pathway in patients with acute abdominal inflammatory processes. 1124 85


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