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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism that explains the association between corticoids and acute pancreatitis is unknown. Our hypothesis was that chronic glucocorticoid treatment could adversely affect the course of hemorrhagic pancreatitis by acting through cholecystokinin (CCK) receptors. Acute necrotizing pancreatitis was induced by feeding young female mice a choline-deficient, ethionine-supplemented (CDE) diet for 60 hours. Treatment with hydrocortisone (10 mg/kg/day) was begun 1 week before pancreatitis. At the onset of the CDE diet, a group of hydrocortisone-treated mice were also given the CCK receptor antagonist CR-1409 (5 mg/kg three times a day). Control mice received injections of saline solution. A follow-up of 336 hours was conducted for survival analysis. Hydrocortisone given alone did not produce pancreatitis. Hydrocortisone, however, did increase the pancreatic necrosis caused by the CDE diet (from 40% to 70%) and significantly reduce survival (from 40% to 9%). CR-1409 completely abolished the adverse effects of hydrocortisone on pancreatitis. We measured amylase release by dispersed pancreatic acini from mice chronically treated with hydrocortisone in response to CCK-8. Treatment with hydrocortisone increased both the sensitivity and the responsiveness of the pancreas to CCK-8. We conclude that glucocorticoids alone may not induce acute pancreatitis, but they can increase the risk of a more severe form of pancreatitis developing. The glucocorticoid effect appears to be attributable to a CCK receptor-mediated sensitization of the pancreas to endogenous CCK. Thus, CCK-receptor blockade may improve survival in necrotizing pancreatitis associated with chronic glucocorticoid treatments.
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PMID:Involvement of cholecystokinin receptors in the adverse effect of glucocorticoids on diet-induced necrotizing pancreatitis. 247 63

Rats infused with a supramaximally stimulating dose of the cholecystokinin (CCK) analog caerulein develop acute edematous pancreatitis. Using CCK-JMV-180, a recently developed CCK analog that acts as an agonist at high-affinity CCK receptors but antagonizes the effect of CCK at low-affinity receptors, we have determined that caerulein induces pancreatitis by interacting with low-affinity CCK receptors. Those low-affinity receptors mediate CCK-induced inhibition of digestive enzyme secretion from the pancreas. Our observations, therefore, suggest that this form of experimental pancreatitis results from the inhibition of pancreatic digestive enzyme secretion.
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PMID:Experimental pancreatitis is mediated by low-affinity cholecystokinin receptors that inhibit digestive enzyme secretion. 247 32

Supramaximal doses of cholecystokinin induce in vitro submaximal biological responses, desensitization and residual stimulation. In vivo, supramaximal inhibition and oedematous pancreatitis have been reported. The aim of this study was to analyze the in vivo response of the pancreatic secretion of the rat to a wide range of doses of CCK8 and analogs prepared by alterations of the Met(28)-Gly(29) bond, a modification that may lead to potent agonists. We used Boc-[Nle28-Nle31]-CCK(26-33) (1) and derivatives of (1) with the 28-29 peptide bond replaced by CH2-NH (2), CO-CH2 (3), CH2-CH2 (4), NH-CO (5). On infusions, the ED50's (pmol/kg.min) for protein output were 4 for CCK8 and (1), 11 for (3), 40 for (2) and (4), and 860 for (5). The relative order of the in vivo potencies was near to the one determined in vitro on isolated rat acini. On bolus injections, the maximal response was observed with 300 pmol/kg of CCK8, and peaked 10-15 min after the injection. With higher doses of CCK8, the secretory peak was smaller, and was delayed relative to the moment of the injection. Supramaximal doses of CCK analogs induced the same pattern of response; however, the peak injection delay was in some cases smaller than after CCK8. Determination of the plasma CCK levels indicated that the time of peak effect after supramaximal doses of CCK8 was delayed relative to the time of effective maximal plasma CCK levels. This suggests a slow dissociation of CCK8 from one of its pancreatic binding sites in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:External pancreatic secretion in the rat: supramaximal inhibition induced by the cholecystokinin octapeptide [CCK(26-33)] and analogs altered on the 28-29 bond. 248 47

Autotransplants of pancreas in 8 dogs, with exocrine drainage into the urinary bladder, were stimulated in vivo with cholecystokinin-pancreozymin (CCK-PZ). Transplant biopsies, when compared with 6 normal pancreases, showed normal acinar structure by light and electron microscopy 13-18 months after initial surgery; 2 transplants with sutures unintentionally transecting ducts were fibrosed and had duct obstruction. After in vivo stimulation, the normal-appearing transplants produced a 7-fold increase in urinary amylase, and quantitative electron microscopy showed a 50% reduction in mature zymogen granules; there were no intracellular organelle abnormalities prior or subsequent to stimulation. Fibrosed transplants produced lesser urinary amylase both prior to and after stimulation. In vitro stimulation of grafts with normal structure increased amylase secretion from 1.5-2.1-fold. In vitro dose-response showed a maximum at 10(-9)M cholecystokinin-octopeptide (CCK-OP) in transplant and control. The in vivo stimulation is more responsive and may be useful for clinical monitoring of graft survival. In vivo stimulation occurred after induced urinary tract infection; because no pancreatitis ensued, a regimen of trophic stimulation by CCK-PZ was not contraindicated. The bladder tolerated exocrine drainage with no significant change, and bladder infection did not adversely affect the transplant. The islets appeared normal in the transplants by light and qualitative electron microscopic observation; fasting blood glucose and insulin values were normal during the 12-18-month follow-up. Bladder drainage of segmental grafts of pancreas provides a preparation with intact acinar-islet relationships; the present observations suggest that this may permit longer islet survival in the absence of acinar destruction and subsequent fibrosis.
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PMID:Acinar structure and function in canine pancreatic autografts with duct drainage into the urinary bladder. 258 38

Parenteral administration of amino acids has been utilized for the nutritional support of patients with a variety of gastrointestinal disorders including protracted pancreatitis and pancreatic fistulae. However, the effect of parenteral amino acid administration alone on human pancreatic secretion has not been studied. We have studied the short-term effect of parenteral administration of amino acids on pancreatic exocrine secretion in seven healthy men. A double-lumen tube was placed in the duodenum and polyethylene glycol was perfused into the proximal duodenum at the rate of 10 ml/min. A second double-lumen tube was placed in the stomach and bromsulfthalein was perfused into the cardia. Samples of duodenal contents were aspirated and gastric contents recovered during one hour of intravenous saline infusion followed by two hours of an amino acid mixture infusion. Hourly outputs of protein and pancreatic enzymes were determined, correcting for duodenogastric reflux based on concentrations of both markers in the samples. Despite an average increase of 72% in the plasma concentration of the infused amino acids, the outputs of protein, trypsin and amylase did not change significantly during amino acid infusion; the output of lipase decreased significantly during amino acid infusion. Two subjects were given intravenous secretin and cholecystokinin following amino acids; this resulted in increased outputs of protein, trypsin, and amylase in both. We conclude that the parenteral administration of amino acids to healthy young men does not stimulate pancreatic enzyme secretion as measured by the method using duodenal marker perfusion at the rate of 10 ml/min.
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PMID:Effect of parenteral amino acids on human pancreatic exocrine secretion. 258 45

The aim of this study was to examine histologic and biochemical alterations in experimental acute interstitial pancreatitis (AIP) induced by serial repeated supramaximal cholecystokinin-octapeptide (CCK-OP) stimulation in rats. High doses of CCK-OP (60 micrograms/kg body wt) were administered subcutaneously (sc) six times at hourly intervals for 1 d (Group I) or for 3, 5, or 7 d (Group II). Rats were killed after 1, 3, 5, 7, and 10 d in both groups and also after 13, 20, and 27 d in Group II. During the course of the AIP, the morphological alterations were more pronounced in the repeatedly treated rats, but their appearance and disappearance essentially occurred in parallel in the two groups. Increased mitotic activity of the centroacinar and acinar cells were observed in d 5 and rose further even in Group II. The pancreatic weight and the protein and DNA contents reached a minimum on d 5 in both groups. The lowest enzyme activities did not occur in parallel. Thereafter, functional regeneration occurred despite continuing CCK-OP overstimulation in Group II. The toxicity of repeated CCK-OP hyperstimulation, thus, was limited: after its fifth administration, it failed to further aggravate the acute pancreatic damage or prevent the regeneration. This might be explained by a decreased CCK-OP sensitivity of the preexisting acinar cells, and/or increased CCK-OP tolerance of newly-formed ones.
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PMID:Course and regression of acute interstitial pancreatitis induced in rats by repeated serial subcutaneous cholecystokinin-octapeptide injections. 260 83

Calcium homeostasis and exocrine pancreas interact on several levels under both physiologic and pathophysiologic conditions. (1) Calcium ions are important intracellular mediators of cholinergic and hormonal stimulation of the pancreatic acinar cell, and thus play a central role in the stimulus-secretion coupling of ecbolic pancreatic function. (2) The calcium concentration in pancreatic juice is lower than in the interstitial fluid: pancreatic juice calcium is composed of two fractions, one of which is secreted together with enzyme proteins and the other diffuses along paracellular pathways dependent on serum calcium. Disturbed calcium secretion in pancreatic juice can be observed even following slight pancreatic alteration; conversely, disturbed calcium secretion may be of importance in the pathogenesis of chronic calcifying pancreatitis. (3) Hypocalcemia is an important symptom of acute pancreatitis whose pathogenesis has not been fully elucidated. (4) On the other hand, pancreatitis complicates chronic and acute hypercalcemic syndromes though the pathogenic mechanisms is uncertain. Experimental chronic hypercalcemia in animal models causes characteristic pancreatic secretory changes and disturbs the diffusion barrier for calcium. Experimental acute hypercalcemia causes stimulation of pancreatic enzyme secretion and cholecystokinin release. In addition, extracellular calcium has a direct stimulatory effect on pancreatic acinar cells in vitro.
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PMID:[Calcium homeostasis and exocrine pancreas: physiological ans pathological interrelations]. 268 7

Repeated subcutaneous injections of cholecystokinin-octapeptide has brought about an acute interstitial pancreatitis in rats. The aim of the experiment was the study of histological and biochemical alterations with special regard to regeneration phenomena. The treatment was carried out for 1 (group 1), 3,5 and 7 (group 2) days. Morphological alterations were more pronounced in group 2 than in group 1, but the pathological process was principally similar in both groups. Lowest values of pancreatic weight, protein and DNA content were attained in both groups at day 5. After this, protein and DNA started to increase. Hyperstimulation with CCK-OP on day 5 did not increase the degree of pancreas damage, nor did it prevent morphological and functional regeneration. The reason of this may be the decreased CCK-OP sensitivity of pancreatic acinar cells and/or the increased CCK-OP tolerance of newly formed acinar cells.
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PMID:[Morphologic and biochemical changes in acute experimental interstitial pancreatitis]. 274 67

The effects of a potent cholecystokinin (CCK) receptor antagonist, L-364,718, on two forms of experimental acute pancreatitis in mice were evaluated. The antagonist prevented the hyperamylasemia, pancreatic edema, and acinar cell vacuolization that followed administration of a supramaximally stimulating dose of the cholecystokinin analogue cerulein. In contrast, the same dose of L-364,718 (1 mg/kg/6 h) and an even higher dose (10 mg/kg/6 h) failed to prevent the hyperamylasemia, acinar cell necrosis, and mortality that followed administration of a choline-deficient ethionine-supplemented diet. These observations are at variance with those previously reported to follow administration of the relatively weak cholecystokinin antagonist proglumide (Niederau C et al. J Clin Invest 1986;78:1056-63). The observations reported in this communication suggest that cholecystokinin does not play an important role in diet-induced pancreatitis and that CCK receptor antagonists are unlikely to be of benefit in the treatment of clinical acute pancreatitis.
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PMID:Failure of a potent cholecystokinin antagonist to protect against diet-induced pancreatitis in mice. 281 32

The onset, course, and regression of the biochemical and structural alterations associated with pancreatitis induced by various doses of caerulein were studied in the mouse. In addition, the protective effect of secretin was compared with that of the cholecystokinin-receptor antagonists proglumide and benzotript. Subcutaneous or intraperitoneal injections of caerulein induced increases in serum amylase concentration and pancreatic weight and histologic evidence of acute pancreatitis, all effects being dose-related. Cytoplasmic vacuoles were the earliest histologic alterations. As the pancreatitis progressed these vacuoles increased to an enormous size. Interstitial inflammation and acinar cell necrosis were prominent after 6 h, reached a maximum after 12 h, and mostly disappeared after 4 days. During the course of pancreatitis approximately 40% of the acinar cells showed signs of severe degeneration or necrosis at the most effective doses of caerulein. Electron microscopy showed both intact and degenerating granules inside the vacuoles. Signs of basolateral exocytosis of zymogen granules were not observed. During the regression of pancreatitis, focal atrophy was a remarkable histologic finding. Repetitive initiation of pancreatitis (six courses of caerulein injections over 5 wk) produced marked focal atrophy and early fibrosis. High doses of proglumide or benzotript markedly ameliorated both the biochemical and structural alterations induced by caerulein. Secretin, even at very high doses, had only minor protective effects. This study presents a model of acute necrotizing pancreatitis in which the severity of the induced pancreatitis ranges dose-dependently from mild interstitial inflammation to severe necrosis. The ultrastructural alterations described herein support the hypothesis that the trigger mechanism of acute pancreatitis appears to be a primary intracellular event rather than an interstitial event that secondarily damages the acinar cells.
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PMID:Caerulein-induced acute necrotizing pancreatitis in mice: protective effects of proglumide, benzotript, and secretin. 298 80


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