Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.1 (chymotrypsin)
10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect on steatorrhoea of a pH-sensitive enteric-coated pancreatic preparation (Eurobiol 25,000) was compared with a conventional pancreatic enzyme preparation (Eurobiol) in six adult patients with exocrine pancreatic insufficiency. In addition, the fate of orally ingested pancreatic enzymes in the upper digestive tract was evaluated by measuring gastric and duodenal pH, amount of enzymes in the stomach, duodenal enzyme output, and fat absorption at the angle of Treitz for the 4 hours following a standard meal. When compared with placebo, Eurobiol and Eurobiol 25,000 reduced daily faecal fat excretion by 24% (not significant) and 43% (P less than 0.05), respectively. With the conventional preparation, enzyme output and fat absorption at the duodeno-jejunal flexure were significantly improved (P less than 0.05). Marked inter-individual differences in duodenal enzyme recovery (lipase 3% to 80%; chymotrypsin 26% to 100%) and, consequently, in the reduction of steatorrhoea (0% to 67%) were observed, with the gastric emptying rate emerging as a key determinant factor. With the enteric-coated preparation, enzyme output and fat absorption at the duodenojejunal flexure were not significantly improved. Discrepancy between the marked reduction of faecal fat excretion and the low duodenal enzyme recovery could indicate that enzyme delivery from microtablets occurs further down in the small bowel. Efficacy of enteric-coated preparations could be enhanced by adding unprotected enzymes, especially in patients with rapid gastric emptying.
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PMID:Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two pancreatic enzyme preparations. 177 47

This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal.
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PMID:Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. 185 88

In CF-patients physical development is an important prognostic factor. Therefore, maldigestion in consequence of an exocrine pancreatic insufficiency must be payed special attention to. Only the acid-protected microsphere pancreatin preparations should be used for enzyme substitution. In estimating of effectiveness both subjective (pains, tolerance) and particularly objective parameters (balance investigations, stool-weight and -frequency, physical development) should be considered. Referring to this the determination of fecal chymotrypsin-concentration is unsuitable. There are further possibilities for increasing the enzyme efficiency, which could soon become applicable.
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PMID:[Pancreatic enzyme substitution in patients with mucoviscidosis]. 218 24

Pancreatic calcifications are particularly frequent in patients with severe pancreatic insufficiency and long-lasting chronic pancreatitis. To clarify whether calcifications point to a more severe form of the disease, irrespective of its duration, we have retrospectively analyzed patients with chronic pancreatitis submitted to the secretin-cerulein test in our center over a six-year period. Out of 120 patients, calcifications were found in 55. Higher alcohol intake and longer duration of the disease were found in patients with calcifications, compared with patients without calcifications (p less than 0.001). In both groups, lipase and chymotrypsin were more severely impaired than bicarbonate; a greater reduction of pancreatic exocrine function was found in patients with calcifications, compared to those without (p less than 0.001, Mann-Whitney U-test). When the patients were classified according to the duration of the disease or the severity of exocrine function impairment, higher percentages of patients with calcifications were found in the classes with more advanced disease. A log-linear analysis showed that the prevalence of calcifications was associated with pancreatic function impairment, even within the same class of duration of the disease. It is likely that calcifications mark more severe forms of chronic pancreatitis, even in the early phases of the disease.
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PMID:Pancreatic calcifications in patients with chronic pancreatitis. A sign of long-lasting or severe disease? 223 Mar 61

In a double-blind, placebo-controlled, crossover trial, we investigated the effects of the prokinetic drug cisapride in patients with cystic fibrosis and chronic recurrent distal intestinal obstruction syndrome (DIOS). After a baseline period, 17 patients (12.9 to 34.9 years; 12 boys) received, in random order, cisapride (7.5 to 10 mg) and placebo three times daily by mouth, each for 6 months. Gastrointestinal symptoms (flatulence, abdominal pain, fullness, abdominal distension, nausea, anorexia, heartburn, diarrhea, vomiting and regurgitation) were scored three times monthly and physical examinations assessed. At baseline and at each 6-month period, assessment included food intake for 7 days, 3-day stool collection, pulmonary function tests, and abdominal radiographs. During cisapride therapy compared with placebo, there were significant reductions in flatulence (p less than 0.005), fullness, and nausea (p less than 0.05). Patients with the worst symptom scores benefited most from cisapride. With cisapride, 12 patients felt better and three worse (p less than 0.05); physicians judged 11 patients improved and two worse (p less than 0.05). No side effects were noted. There were no significant differences between cisapride and placebo periods in nutritional status, x-ray scores, pulmonary function, food intake (fat, protein, calories), stool size and consistency, and fecal losses of fat, bile acids, chymotrypsin, and calories. For acute episodes of DIOS, intestinal lavage was needed 6 times in 4 patients during treatment with cisapride, and 11 times in 6 patients receiving placebo. In comparison with unselected patients with cystic fibrosis and pancreatic insufficiency who were receiving enzyme supplements and who had no distal intestinal obstruction, fecal fat losses (percentage of intake) were almost twice as high in the study group with DIOS (31.2 +/- 20.6% vs 16.2 +/- 17.6%; p less than 0.01). We conclude that in the dosage used, long-term treatment with cisapride appears to improve chronic abdominal symptoms in patients with cystic fibrosis and DIOS, but fails to abolish the need for intestinal lavage. Cisapride treatment had no effect on digestion and nutritional status of cystic fibrosis patients with pancreatic insufficiency.
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PMID:Effects of cisapride in patients with cystic fibrosis and distal intestinal obstruction syndrome. 223 Dec 17

The diagnostic value of a new enzyme immunoassay for lipase (IRL) was evaluated in controls (n = 65), in acute pancreatitis (n = 11) and in extrapancreatic hyperamylasemia (n = 15) by comparing IRL with serum amylase (TA), pancreatic isoamylase (PA) and lipase (turbidimetrically: TL). IRL and immunoreactive trypsin (IRT) of 60 patients with alcoholic chronic calcified pancreatitis were also studied and correlated with duration of disease and degree of pancreatic insufficiency (based on fecal chymotrypsin test: FCT). IRL was constantly elevated in patients with acute pancreatitis. In extrapancreatic hyperamylasemia IRL was mainly normal, in contrast to PA, which was elevated in 7 patients with macroamylasemia. In 56.7% of all patients with chronic pancreatitis, IRL was pathologically low; in association with advanced insufficiency (FCT less than 20 micrograms/g) this figure was 74%, and after duration of disease of greater than or equal to 15 years 77%. For IRT comparable results were found in 79% and 77% respectively. This new lipase test thus seems to be useful for the diagnosis of acute pancreatitis, the differential diagnosis of extrapancreatic hyperamylasemia and the detection and monitoring of severe chronic pancreatitis.
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PMID:[Significance of immunoreactive lipase in the diagnosis of pancreatic diseases]. 241 82

Pancreatic insufficiency was induced in rats by a single injection of 50 microliter oleic acid into the pancreatic duct over a period of 3 min. Exocrine tissue was destroyed within 3-6 days, and after 6 weeks the remaining pancreas equaled 2.7% of the original organ. The rats showed retardation of body weight in spite of normal food intake. After 7 weeks the fecal weight increased by 23%, and the fecal chymotrypsin activity decreased by 90% compared to controls. At this time plasma cholecystokinin (CCK) concentrations were significantly elevated. The amylase content in the remaining pancreas was reduced by 99%, and trypsin content was reduced by 93%. Unstimulated protein discharge from the remnant pancreas in vitro was threefold higher compared to secretion from control tissue. Thus a simple, reproducible model for inducing persistent pancreatic insufficiency was developed. To compensate for the loss of exocrine tissue, the remaining acinar cells adapt by a CCK-mediated increase in protein secretion.
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PMID:Exocrine pancreatic function in oleic acid-induced pancreatic insufficiency in rats. 243 60

Oral pancreatic enzyme replacement therapy generally benefits patients with severe pancreatic deficiency. However, the fate of oral pancreatic supplements in the digestive lumen and their possible effects on circulating gut hormones are only partially known. The purpose of this article is to validate an experimental model that produces total pancreatic insufficiency in pigs, and to study the fate of orally administered Eurobiol, a whole pancreas lyophilized preparation, and its effects on circulating plasma levels of five digestive hormones. Pancreatic insufficiency was created by pancreatic duct ligation, and the duodenal, jejunal and ileal contents were sampled through cannulas before a normal meal and 0.5-24 h later. Blood samples were taken at the same times, and plasma neurotensin, pancreatic polypeptide, secretin, cholecystokinin (CCK), and gastrin were measured. In pigs with pancreatic insufficiency, Eurobiol, given during the meal, induced a significant increase in all enzyme activities in the duodenum and the jejunum, and in the levels of amylase, trypsin, and chymotrypsin in the ileum, relative to placebo. In the duodenum, the peak concentrations of enzyme activities were 19, 11, 17, and 29% (p less than 0.001) of the postprandial peak activities measured in control pigs with an intact pancreas for lipase, amylase, trypsin, and chymotrypsin, respectively. In the jejunum, the same activities were, respectively, 30, 11, 25, and 36% (p less than 0.01-0.001) of normal peaks. In pigs with pancreatic insufficiency, basal and integrated meal-stimulated neurotensin levels were increased; basal, peak, and integrated meal-stimulated pancreatic polypeptide and secretin levels were increased, whereas gastrin and CCK were not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Total pancreatic insufficiency in pigs: a model to study intestinal enzymes and plasma levels of digestive hormones after pancreatic supplementation by a whole pancreas preparation. 247 98

Random fecal chymotrypsin activity and fecal alpha 1-antitrypsin (FA-1-AT) concentrations were determined in 11 children with cystic fibrosis, 5 children with Crohn's disease, 9 children with chronic aspecific diarrhea, 85 children with acute gastroenteritis, and 54 control children. Cystic fibrosis patients showed only very low fecal chymotrypsin values that did not overlap with values obtained in patients with either acute or chronic diarrhea. When compared with our control group, a significant increase of FA-1-AT concentrations was found only in children with Crohn's disease. Normal values were found in all patients with either chronic aspecific diarrhea or cystic fibrosis, while 12 of 85 children with acute gastroenteritis showed FA-1-AT concentrations above the 95th percentile of control children. We conclude that diarrhea (either acute or chronic) does not significantly decrease the clinical usefulness of fecal chymotrypsin activity measurements in the diagnosis of pancreatic insufficiency, while acute (gastroenteritis) but not chronic (chronic aspecific diarrhea, cystic fibrosis) diarrhea can give rise to protein losing and FA-1-AT concentrations similar to those found in Crohn's disease.
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PMID:Usefulness of random fecal alpha 1-antitrypsin and chymotrypsin determinations in children. 278 61

A breath test for the detection of pancreatic insufficiency was developed and tested in rats. The test features the hydrophobic molecule cholesteryl-1-14C-octanoate, which liberates 14C-octanoic acid when hydrolyzed by carboxyl ester lipase (cholesterol esterase). The 14C-octanoate is absorbed passively and rapidly metabolized to 14CO2, which is excreted in expired air. The compound was administered as an emulsion of cholesteryl octanoate, triglyceride, and lecithin to rats with mild pancreatic insufficiency induced by injecting the pancreatic duct with zein. The animals had exocrine pancreatic hypofunction based on the enzyme content of pancreas at autopsy. Amylase was reduced by 97.1 +/- 1.4%, whereas chymotrypsin was reduced by 73 +/- 14%. The p-aminobenzoic acid test was abnormal at 1 wk (21.68 +/- 8.4%), but become normal at 3 months (72.08 +/- 5.8%) after zein injection. Despite this, the animals gained weight and absorbed fat normally. The 14CO2 excretion rate in the 110-min interval after feeding was significantly reduced to 60% of sham-operated animals. Peak 14CO2 collections 20 min after feeding were reduced by 75 +/- 11%. 14CO2 output was completely normalized by administration of pancreatin prior to the test meal. The results suggest that a sensitive, noninvasive method for detecting deficiency of pancreatic carboxyl ester lipase (cholesterol esterase) secretion in the rat has been developed.
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PMID:The cholesteryl octanoate breath test: a new procedure for detection of pancreatic insufficiency in the rat. 311 94


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