Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three-dimensional magnetic resonance cholangiopancreatography is currently the most exciting new imaging technique for chronic pancreatitis. Endoscopy-assisted duodenal intubation during the secretin-cholecystokinin test reduces intubation time in difficult cases. The NBT-para-amino benzoic acid test has been refined to enhance its discriminant power. The cholesteryl-[C13]octanoate breath test and the faecal elastase test are newer highly sensitive and specific tubeless tests. Pain in chronic pancreatitis continues to be a vexing therapeutic issue. Enzyme treatment continues despite criticism. Neurotensin is the new suspected mediator of the feedback mechanism, which is downregulated by enzyme therapy. Steroid ganglion block is an exciting therapeutic tool for pain relief. Endoscopic pancreatic sphincterotomy, Dormia basketing and pancreatic stenting in conjunction with extracorporeal shock wave lithotripsy should be performed early in chronic pancreatitis to prevent parenchymal atrophy with ensuing exocrine and endocrine pancreatic dysfunction. The modified Puestow's procedure preserves endocrine and exocrine pancreatic functions besides relieving pain. Closed loop insulin infusion allows superior management of pancreatic diabetes following near total pancreatectomy. The standardised incidence rate of pancreatic cancer is 16.5 in patients with alcoholic chronic pancreatitis and 100 for tropical chronic pancreatitis. Aggressive treatment protocols combining neo-adjuvant chemoradiation and intra-operative radiation with surgery are being used to improve the prognosis in this dismal complication of chronic pancreatitis.
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PMID:Chronic pancreatitis: diagnosis and treatment. 875 8

The effect of oral administration of protease inhibitor (camostat) on pancreatic morphology and exocrine function (conscious rat model) was investigated using WBN/Kob rats with spontaneous chronic pancreatitis. In nontreated WBN/Kob rats (2-12 months of age), pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis appeared at 3 months and advanced with each month. Pancreatic secretion was markedly impaired at all ages. In WBN/Kob rats fed diets containing camostat (from 2-3 or 4-5 months of age), the pancreas was hypertrophic and did not show any histological appearances compatible with chronic pancreatitis, and moreover, exocrine function was thoroughly restored with increased plasma cholecystokinin concentrations. Oral administration of protease inhibitor has both preventive and therapeutic effects on pancreatic lesions and dysfunction in an animal model of chronic pancreatitis, probably via endogenous cholecystokinin release.
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PMID:Effect of oral administration of protease inhibitor on pancreatic exocrine function in WBN/Kob rats with chronic pancreatitis. 878 37

Tiscornia and Dreiling (Physiopathogenic Hypothesis of Alcoholic Pancreatitis: Supranormal Ecbolic Stimulation of the "Pancreon" Units Secondary to the Loss of the Negative Component of Pancreas Innervation. Pancreas 1987;2:604-612.) proposed that hypertonicity of intrapancreatic cholinergic neurons provoked by chronic alcoholism may contribute to the pathogenesis of chronic pancreatitis (CP). In the present study, the validity of this hypothesis was investigated in humans by studying the effects of atropine, cisapride, and ethanol on the meal-stimulated secretion of pancreatic polypeptide (PP) and cholecystokinin (CCK) in healthy volunteers, heavy drinkers, and CP patients. In healthy volunteers, the early phase PP response (0-40 min) to a test meal was completely blocked by atropine, whereas it was augmented by cisapride, an enhancer of acetylcholine release from cholinergic nerves. The early phase PP response to a test meal was inhibited by ethanol in healthy volunteers, whereas, in heavy drinkers, the response was augmented and the inhibition by ethanol was abrogated. In CP patients, ethanol tended to enhance the early phase PP response. Ethanol did not affect the early phase CCK response to a test meal in any group, but it significantly enhanced the late phase CCK response (40-120 min) in CP patients. These results suggest that: (i) oral ethanol may inhibit the postprandial activation of the cholinergic neural pathway to the pancreas in healthy subjects, (ii) in heavy drinkers, postprandial cholinergic tone may be augmented and become resistant to the inhibition by ethanol, and (iii) the ethanol-induced increase in the postprandial CCK response in CP patients may play some role in the pathophysiology of this disease.
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PMID:Effects of ethanol on meal-stimulated secretion of pancreatic polypeptide and cholecystokinin: comparison of healthy volunteers, heavy drinkers, and patients with chronic pancreatitis. 880 34

Exocrine pancreas from different species behaves differently in response to the presence of intact or digested nutrients in the duodenum. A failure of cholecystokinin (CCK) release after a meal has been shown among patients with exocrine pancreatic insufficiency. This abnormality could be restored by the administration of pancreatic extracts, suggesting that digested rather than intact nutrients are responsible for the release of CCK and subsequently gallbladder contraction in humans. The aim of this study was to determine the specific role of different lipidic stimuli in humans. Seven male patients (mean age, 52 years) with pancreatic insufficiency secondary to chronic pancreatitis were selected. Pancreatic insufficiency was considered severe in five of them (lipase output, < 1,000 IU/min) and moderate in another two (lipase output, > 1,000 and < 2,300 IU/min). Plasma CCK (by bioassay), gallbladder contraction (by ultrasound), and enzyme output (chymotrypsin) in response to duodenal administration of either oleic acid as free fatty acids or 20% Intralipid as triglycerides were measured in each patient with at least a 48-h interval between each test. In all these patients with pancreatic insufficiency, duodenal perfusion of free fatty acids generated a more pronounced (91 +/- 11 vs. 49 +/- 21 pM) and faster (15 vs. 30 min) (p < 0.05) CCK release than triglycerides. Furthermore, gallbladder contraction was more efficient when free fatty acids instead of triglycerides were administered in the duodenum (86 +/- 5 vs. 69 +/- 4%) at 10 min (p < 0.05) and (73 +/- 8 vs. 51 +/- 5%) at 15 min (p < 0.03). Among patients with measurable residual pancreatic function, enzyme outputs were shown to be higher during free fatty acid than triglyceride perfusion. In humans, free fatty acids rather than triglycerides, when present in the duodenum, stimulate CCK release and gallbladder contraction. In patients with moderate pancreatic insufficiency this phenomenon may increase residual enzymatic secretion. These results allow us to encourage the development of enzymatic preparations as acid-resistant lipases that cause a fast release of free fatty acids in the duodenum.
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PMID:Intraduodenal free fatty acids rather than triglycerides are responsible for the release of CCK in humans. 898 11

Oral administration of a protease inhibitor (camostat) induces pancreatic hypersecretion via hormonal and neural systems in humans. Camostat may also affect gallbladder motility via these systems. The aim of this study was to evaluate the effect of camostat on gallbladder function. Gallbladder emptying in response to caerulein administration and to egg yolk ingestion was examined ultrasonographically in 15 patients with mild chronic pancreatitis before and after 6 months of camostat treatment, and in 10 control subjects. The plasma cholecystokinin concentration after yolk ingestion was measured by radioimmunoassay. Fasting gallbladder volume and contractile function, whether stimulated by caerulein or yolk, did not differ between pancreatitis patients before camostat treatment and controls. Plasma cholecystokinin levels, basal and yolk-stimulated, did not differ between nontreated pancreatitis patients and control subjects. Fasting volume had decreased significantly by 1, 3, and 6 months of camostat treatment, while contractile function was not affected. Camostat did not influence plasma cholecystokinin levels. Oral administration of a protease inhibitor appears to decrease fasting gallbladder volume via a mechanism other than cholecystokinin release.
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PMID:Effect of oral protease inhibitor administration on gallbladder motility in patients with mild chronic pancreatitis. 921 53

Cholecystokinin (CCK) response to a test meal should be increased in patients with pancreatic insufficiency, as trypsin is absent from the duodenum. If pancreatic enzymes are added, a restoration of the inhibitory feedback should result in lower levels of CCK. Ten patients with chronic pancreatitis and steatorrhea were studied. CCK basal and postprandial levels were evaluated the day before and 45 and 90 days after treatment with oral pancreatin. Twelve healthy volunteers were included as reference group. CCK basal levels did not vary. CCK response to a test meal was increased in patients before treatment and diminished when oral enzymes were maintained for months even after three days of therapy withdrawal. We conclude that long-term therapy with oral enzymes induces changes in CCK response that do not regress after three days of treatment suspension.
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PMID:Postprandial cholecystokinin response in patients with chronic pancreatitis in treatment with oral substitutive pancreatic enzymes. 953 52

The efficacy of medications to treat pancreatic diseases, even when proven effective by experimental studies, are difficult to prove by controlled clinical trials. In the treatment of acute pancreatitis, prophylactic antibiotics, somatostatin, protease inhibitors, and cholecystokinin (CCK)-receptor antagonists are advocated for use in the early stages of acute pancreatitis, but the data are insufficient to mandate prophylaxis use or recommend their use as a standard of care. In the treatment of chronic pancreatitis, digestive enzymes, oral active protease inhibitors, CCK-receptor antagonists, or somatostatin are administered for pain relief. Extracorporeal shock-wave lithotripsy and oral dissolution therapy with trimethadione are used to treat pancreatic stones. The goals of treatment of acute pancreatitis should be to ameliorate the severity of pancreatic inflammation or to prevent its complications. Although several treatments seem to be promising from the studies reviewed, these medications require prospective comparison with the standard procedures and long-term evaluation.
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PMID:Pharmaceutical development for treating pancreatic diseases. 954 90

We compared pancreatic exocrine secretion in 5-month-old WBN/Kob rats, a model of chronic pancreatitis, with that in Wistar rats of the same age in a conscious state. Basal pancreatic secretion and pancreatic wet weight in WBN/Kob rats were lower than the values for Wistar rats. There was no difference in plasma cholecystokinin (CCK) concentration between the two types of rats. When CCK-8 was intravenously administered, the stimulation of pancreatic protein secretion in WBN/Kob rats was weaker than that in Wistar rats. When bile and pancreatic juice were diverted from the duodenum, the resulting increase in the plasma CCK concentration was similar in both types of rats, but stimulation of the volume and protein output of pancreatic juice in WBN/Kob rats was weaker than that in Wistar rats. In addition, WBN/Kob rats exhibited little increase in pancreatic wet weight because of this diversion. When secretin was intravenously administered, the stimulation of fluid secretion in WBN/ Kob rats was also weaker than that in Wistar rats. The binding of CCK-8 to pancreatic membrane fractions in WBN/Kob rats was much weaker than that in Wistar rats. Histological findings in WBN/Kob rat pancreas showed proliferation of fibrous tissue and atrophy of acinar cells. In conclusion, pancreatic exocrine secretion in response to the gastrointestinal hormones, CCK and secretin, was lower in WBN/Kob rats than in Wistar rats. These findings suggest that the hyposecretion of pancreas in WBN/Kob rats is hyporeaction of pancreatic membrane to gastrointestinal hormones.
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PMID:Reduced reactivity of pancreatic exocrine secretion in response to gastrointestinal hormone in WBN/Kob rats. 960 57

Release of GP2, a glycosyl phosphatidylinositol-linked protein on the apical plasma membrane of the pancreatic acinar cell, is associated with activation of endocytosis. Released GP2 is also an integral component of intraductal plugs in patients with alcohol-induced chronic pancreatitis. Our purpose was to determine the effect of ethanol on exocytosis and endocytosis and its association with release of membrane-bound GP2. Rats were fed Lieber-DeCarli diets with and without ethanol for 2 weeks. Endocytosis was then assessed in acini by measuring horseradish peroxidase (HRP) uptake, GP2 release by Western blotting, and exocytosis by measuring amylase release. In ethanol-fed rats, HRP uptake was inhibited by 90% compared to that in control rats. In contrast, no significant difference in cholecystokinin-stimulated amylase secretion was found. In vitro, ethanol inhibited HRP uptake in a dose-dependent manner, with 50% inhibition at 50 mM ethanol. Despite the inhibition of endocytosis, GP2 release increased linearly over 60 min and was significantly higher from acini incubated with ethanol compared to controls. These data indicate that ethanol selectively inhibits endocytosis in pancreatic acinar cells. The release of GP2 into the pancreatic duct was no longer coupled to endocytosis in animals fed ethanol.
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PMID:Chronic ethanol administration selectively impairs endocytosis in the rat exocrine pancreas. 970 Sep 42

The effect of FK480, a cholecystokinin-A (CCK-A) selective receptor antagonist, on spontaneously developed chronic pancreatitis was examined in WBN/Kob rats. Animals at age 18 weeks (18w-Control) already had the histologic appearance of chronic pancreatitis as indicated by inflammatory cell infiltration and fibrotic degeneration with interstitial edema. Rats treated with vehicle from 18 to 26 weeks of age (26w-Control) showed further development of pancreatitis as characterized by more extensive appearance of inflammatory cell infiltration and fibrotic changes, with the pancreatic weight significantly decreased. Serum amylase levels of 26w-Control animals were slightly decreased compared with those of 18w-Control animals, although the difference was not statistically significant. When rats were treated orally with 1, 10, and 100 microg/kg FK480 from 18 to 26 weeks of age, the decrease in serum amylase levels recovered dose dependently compared with 26w-Control, and the level in animals treated with 100 microg/kg FK480 was almost the same as that in 18w-Control rats. Histologic examinations revealed that the appearance of the pancreas of animals treated with FK480 was slightly improved with respect to inflammatory cell infiltration and edematous changes at the highest dose examined, although the difference was not statistically significant. Although blockade of the CCK-A receptor could be considered to exacerbate chronic pancreatitis due to possible inhibition of the trophic action of CCK, our results suggest that CCK-A receptor antagonists may not be detrimental to chronic pancreatitis.
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PMID:Effect of FK480, a CCK-A receptor antagonist, on spontaneously developed chronic pancreatitis in WBN/Kob rats. 978 45


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