alpha-chymotrypsin and Celiac-Disease

We sought to determine whether prolyl endopeptidase (PEP) treatment of food gluten would obviate the intestinal dysfunction produced by small amounts of dietary gluten supplement in patients with celiac sprue.. Twenty asymptomatic patients with histologically proven celiac sprue completed a randomized, double-blind, cross-over study involving two 14-day stages. Each patient consumed a low dose of a gluten supplement daily (5 g; equivalent to 1 slice of bread) in 1 stage and gluten pretreated with PEP in the other stage. Patients completed a daily symptom questionnaire and a D-xylose urine excretion and a 72-hour quantitative fecal fat were monitored before and after each stage.. Despite clinical remission at baseline, 40% of patients had at least 1 abnormal celiac antibody, 20% had an abnormal urine xylose, and 63% had an abnormal fecal fat test result. There was no difference in symptoms as a function of the type of gluten consumed. In response to gluten not treated with PEP, an appreciable proportion of patients developed malabsorption of fat (7 of 17, 41%) or xylose (8 of 14, 57%). When the gluten was pretreated with PEP, fat malabsorption was avoided in 5 of 7 and xylose malabsorption in 4 of 8 of these same patients.. A significant proportion of asymptomatic patients with celiac sprue have abnormal celiac antibodies and fat or carbohydrate malabsorption. Pretreatment of gluten with PEP avoided the development of fat or carbohydrate malabsorption in the majority of those patients who developed fat or carbohydrate malabsorption after a 2-week gluten challenge.

Topics: Adult; Aged; Celiac Disease; Chymotrypsin; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Female; Gastrointestinal Agents; Glutens; Humans; Male; Middle Aged; Pepsin A; Prolyl Oligopeptidases; Serine Endopeptidases; Trypsin

Nutrient malabsorption is a negative prognostic factor in acquired immunodeficiency syndrome and recent studies have shown that pancreatic insufficiency is a codetermining factor of malabsorption.. To evaluate the effectiveness of open-label oral pancreatic enzyme supplementation therapy in acquired immunodeficiency syndrome patients with fat malabsorption.. Twenty-four consecutive patients with human immunodeficiency virus infection and fat malabsorption were recruited (11 males, 13 females; median age, 9.1 years). Faecal fat loss was evaluated by steatocrit assay at entry to the study (T-0), after 2 weeks (T-1) without pancreatic enzyme treatment and after a further 2 weeks (T-2) of treatment with pancreatic extracts (Creon 10 000 at a dose of 1000 units of lipase per gram of ingested dietary fat). Faecal elastase-1 and chymotrypsin were assayed at entry.. Six patients (25%) had abnormally low elastase-1 and/or chymotrypsin faecal concentration. In all patients, steatocrit values were elevated at both T-0 and T-1. Five patients proved intolerant to pancreatic enzyme treatment because of the onset of abdominal pain, and therapy was discontinued. In the 19 patients who concluded the study, steatocrit values during pancreatic enzyme treatment (T-2) were significantly lower than at entry (P < 0.0001). At T-2, in eight of 19 patients, steatocrit values were within the normal limit and the frequency of cases cured or improved on pancreatic enzyme therapy (at T-2) was significantly higher than that observed during the previous study period without enzyme treatment (T-1) (P < 0.01). A positive significant correlation was found between steatocrit values at entry and the Centers for Disease Control class (P < 0.0005); also, the decrease in steatocrit values during pancreatic enzyme therapy (difference between steatocrit value at T-2 and steatocrit value at T-0) positively correlated with the Centers for Disease Control class (P < 0.05).. This pilot, open-label study showed that pancreatic enzyme supplementation therapy is highly effective in reducing faecal fat loss in human immunodeficiency virus-infected patients with nutrient malabsorption. Further double-blind studies must be undertaken to verify these results and, if they are confirmed, pancreatic enzymes can be added to our weapons in the fight against human immunodeficiency virus-associated nutrient malabsorption.

Topics: Adolescent; Celiac Disease; Child; Child, Preschool; Chymotrypsin; Exocrine Pancreatic Insufficiency; Fats; Feces; Female; HIV Infections; Humans; Infant; Intestinal Absorption; Male; Pancreatic Elastase; Pancreatic Function Tests; Pancrelipase; Treatment Outcome

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.

Topics: Adult; Bile Acids and Salts; Celiac Disease; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Gastric Emptying; Humans; Lipase; Male; Middle Aged; Pancreatic Extracts; Tablets, Enteric-Coated

Topics: Adult; Aged; Celiac Disease; Cholecystokinin; Chymotrypsin; Clinical Trials as Topic; Colonic Diseases, Functional; Feces; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Diseases; Secretin

Bile acids deactivate certain enzymes, such as prolyl endopeptidases (PEPs), which are investigated as candidates for protease-based therapy for celiac sprue. Deactivation by bile acids presents a problem for therapeutic enzymes targetted to function in the upper intestine. However, enzyme deactivation by bile acids is not a general phenomenon. Trypsin and chymotrypsin are not deactivated by bile acids. In fact, these pancreatic enzymes are more efficient at cleaving large dietary substrates in the presence of bile acids. We targeted the origin of the apparently different effect of bile acids on prolyl endopeptidases and pancreatic enzymes by examining the effect of bile acids on the kinetics of cleavage of small substrates, and by determining the effect of bile acids on the thermodynamic stabilities of these enzymes. Physiological amounts (5 mM) of cholic acid decrease the thermodynamic stability of Flavobacterium meningosepticum PEP from 18.5 ± 2 kcal/mol to 10.5 ± 1 kcal/mol, while thermostability of trypsin and chymotrypsin is unchanged. Trypsin and chymotrypsin activation by bile and PEP deactivation can both be explained in terms of a common mechanism: bile acid-mediated protein destabilization. Bile acids, usually considered non-denaturing surfactants, in this case act as a destabilizing agent on PEP thus deactivating the enzyme. However, this level of global thermodynamic destabilization does not account for a more than 50% decrease in enzyme activity, suggesting that bile acids most likely modulate enzyme activity through specific local interactions.

Topics: Alphaproteobacteria; Bacterial Proteins; Bile Acids and Salts; Biocatalysis; Celiac Disease; Chryseobacterium; Chymotrypsin; Enzyme Activation; Enzyme Stability; Humans; Kinetics; Pancreas; Prolyl Oligopeptidases; Serine Endopeptidases; Trypsin

Exocrine pancreatic function in patients with cystic fibrosis (CF) can be evaluated by direct and indirect tests. In pediatric patients, indirect tests are preferred because of their less invasive character, especially in CF patients with respiratory disease. Fecal tests are noninvasive and have been shown to have a high sensitivity and specificity. However, there is no comparative study in CF patients. Therefore, the aim of the present study was to compare the sensitivity and the specificity of the fecal elastase-1 (E1) test with the fecal chymotrypsin (ChT) test in a large cohort of CF patients and healthy subjects (HS).. One hundred twenty-three CF patients and 105 HS were evaluated. In all subjects, E1 concentration and ChT activity were measured. In the CF group, fecal fat excretion was also determined. The sensitivity and specificity of the fecal E1 test and ChT test were compared.. With a cutoff level of 3 U/g, ChT specificity in HS was similar to that of E1, but E1 sensitivity in CF patients was significantly higher (90.2% vs 81.3%). With a cutoff level of 6 U/g, ChT and E1 sensitivity in CF patients was identical, but E1 specificity in HS was again significantly higher (98.1% vs 90.5%). In all CF patients with severe steatorrhea (>15 g/d), E1 concentrations were abnormal and ChT activity was lower than 3 U/g. In contrast, in pancreatic-sufficient patients and patients with mild steatorrhea (< or =15 g/d), the E1 sensitivity was significantly higher compared with ChT (69.2% vs 41.0%).. The fecal E1 test is superior to fecal ChT determination in the assessment of CF pancreatic involvement in pancreatic-sufficient patients and those patients with mild steatorrhea.

Topics: Adolescent; Adult; Celiac Disease; Child; Child, Preschool; Chymotrypsin; Clinical Enzyme Tests; Colorimetry; Cystic Fibrosis; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Infant; Male; Pancreas; Pancreatic Elastase; Pancreatic Function Tests; Sensitivity and Specificity

Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T cell responses to ingested wheat gliadins. Initial studies used gliadin that had been subjected to non-enzymatic deamidation during pepsin/trypsin digestion to enrich for the gliadin-specific T cells in small intestinal celiac biopsies. These T cells recognized synthetic gliadin peptides only after their deamidation in vitro by purified tissue transglutaminase (tTG). However, as these studies used a deamidated antigen for re-stimulation prior to testing for antigen specificity, this raised the possibility that T cells specific for native epitopes had not been expanded in vitro and had thus been overlooked. To address this possibility and to look for more direct evidence that endogenous tTG mediates deamidation of gluten in the celiac lesions, we have here used a minimally deamidated chymotrypsin-digest of gliadin to challenge biopsies and then investigated the specificity of the T cell lines derived from them. Interestingly, these T cell lines only barely responded to the chymotrypsin-digested gliadins, but efficiently recognized the in vitro tTG-treated variants of the same gliadins. Moreover, the addition of a tTG-inhibitor during the gliadin challenge often resulted in T cell lines with abolished or reduced responses to deamidated gliadin. These data demonstrate that DQ2-restricted T cells within adult celiac lesions predominantly recognize deamidated gliadin epitopes that are formed in situ by endogenous tTG.

Topics: Amides; Antigen-Presenting Cells; Biopsy; Celiac Disease; Cells, Cultured; Chymotrypsin; Cystamine; Epitopes, T-Lymphocyte; Gliadin; Humans; Intestines; Lymphocyte Activation; T-Lymphocytes; Transglutaminases

Treatment of human exocrine pancreatic insufficiency is suboptimal. This study assessed the effects of bacterial lipase, porcine lipase, and diets on carbohydrate, fat, and protein absorption in pancreatic-insufficient dogs.. Dogs were given bacterial or porcine lipase and 3 diets: a 48% carbohydrate, 27% fat, and 25% protein standard diet; a high-carbohydrate, low-fat, and low-protein diet; or a low-carbohydrate, high-fat, and high-protein diet (66%/18%/16% and 21%/43%/36% calories).. With the standard diet, coefficient of fat absorption increased dose-dependently with both lipases (P < 0.05), but more fat was absorbed with porcine lipase (P < 0.05); 600, 000 IU of bacterial lipase (240 mg) and 300,000 IU of porcine lipase (18 g) nearly abolished steatorrhea. With 300,000 IU of bacterial lipase or 135,000 IU of porcine lipase, fat absorption was greater with the high-fat and -protein diet (P < 0.05 vs. low-fat and -protein diet). There were no interactions among carbohydrate, fat, and protein absorption.. Correcting steatorrhea requires 75 times more porcine than bacterial lipase (18 vs. 240 mg). High-fat and high-protein diets optimize fat absorption with both enzymes. High-fat diets with bacterial or porcine lipase should be evaluated in humans with pancreatic steatorrhea.

Topics: Animals; Bacteria; Bacterial Proteins; Celiac Disease; Chymotrypsin; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Dogs; Dose-Response Relationship, Drug; Exocrine Pancreatic Insufficiency; Intestinal Absorption; Lipase; Swine; Trypsin

The aim of this study was to determine the prevalence of steatorrhea in patients with Graves' disease and to assess its significance and correlation with changes in body mass index (BMI), coefficient of fat absorption (COFA), and pancreatic exocrine function in these patients.. Daily dietary fat intake, 24 h fecal fat, COFA, fecal chymotrypsin activity (as an index of pancreatic exocrine function), and total T3, T4, and TSH levels were assessed in 28 patients with active Graves' disease. In 24 patients, reassessment was done after attaining a euthyroid state with carbimazole therapy.. In the thyrotoxic state, 13 of 28 patients had steatorrhea, whereas 15 had normal (<6 g/day) fat excretion (11.4 +/- 6.7 g vs 2.9 +/- 0.8 g, p = 0.0007). Daily fat intake, basal BMI, and serum T3 and T4 levels were similar in the steatorrheic and nonsteatorrheic groups. The mean COFA of the steatorrheic group was significantly lower than that of nonsteatorrheic group (91.6% +/- 4.8% vs 97.7% +/- 0.9%, respectively; p = 0.0006). In the steatorrheic group, fat excretion and COFA normalized after attainment of euthyroidism (changes in fat excretion and COFA = 7.3% +/- 6.3 g/day and 7.7% +/- 5.4%, respectively). Fecal chymotrypsin levels were similar in the steatorrheic and nonsteatorrheic thyrotoxics and in 16 healthy control subjects. The levels did not show any significant changes following attainment of euthyroid status.. Steatorrhea associated with a decrease in COFA can occur in a reversible manner in 46% of patients with Graves' disease. However, steatorrhea in these patients is not linked with weight loss or with pancreatic exocrine dysfunction.

Topics: Absorption; Adult; Antithyroid Agents; Body Mass Index; Carbimazole; Case-Control Studies; Celiac Disease; Chymotrypsin; Dietary Fats; Feces; Female; Follow-Up Studies; Graves Disease; Humans; Lipids; Male; Pancreas; Prevalence; Thyrotoxicosis; Thyrotropin; Thyroxine; Triiodothyronine; Weight Loss

Nutrient malabsorption frequently occurs in HIV infected children, but very few studies have investigated exocrine pancreatic digestive capacity in these cases.. To investigate pancreatic function in HIV infected children and to determine whether faecal fat loss, a prominent feature of intestinal dysfunction, is associated with pancreatic dysfunction.. Forty seven children with HIV infection without apparent pancreatic disease and 45 sex and age matched healthy controls.. Pancreatic function was evaluated by measuring elastase 1 concentration and chymotrypsin activity in stools by ELISA and colorimetric methods, respectively. Intestinal function was evaluated by measuring fat and protein loss by the steatocrit method and by faecal alpha1 antitrypsin concentration.. 14 (30%) had abnormal pancreatic function tests: seven had isolated elastase activity deficiency, three isolated chymotrypsin deficiency, and four pancreatic deficiencies in both enzymes. Patient enzyme values were significantly lower than those of controls. Low faecal pancreatic enzymes were not associated with symptoms. Twelve children had steatorrhoea and four had increased alpha1 antitrypsin. Steatorrhoea was significantly associated with reduced faecal pancreatic enzymes. There was a significant negative correlation between elastase 1 concentration and steatocrit. Children with pathological faecal elastase 1 or chymotrypsin values did not differ from the other HIV infected children with respect to nutritional and immunological status, stage of HIV disease, presence of opportunistic infections, or drug administration.. Abnormal pancreatic function tests are a frequent feature of paediatric HIV infection; this condition is associated with steatorrhoea, which probably contributes to the disease.

Topics: Adolescent; Case-Control Studies; Celiac Disease; Child; Child, Preschool; Chymotrypsin; Dietary Fats; Enzyme-Linked Immunosorbent Assay; Feces; Female; HIV Infections; Humans; Infant; Intestinal Absorption; Malabsorption Syndromes; Male; Pancreatic Diseases; Pancreatic Elastase; Prospective Studies

Clinical significance and duration of insufficient release of pancreatic enzymes in childhood celiac disease have not been clarified. The aim of this study was to evaluate the role that pancreatic impairment plays in growth recovery and the duration of this impairment.. Forty-six patients with celiac disease who had a median age of 2.5 years were enrolled. Fecal chymotrypsin level was determined at diagnosis and then every 15 days after the beginning of a gluten-free diet in all patients.. At diagnosis, 17 of 46 patients with celiac disease had subnormal fecal chymotrypsin values. During the gluten-free diet, a progressive reduction in the percentage of patients with subnormal fecal chymotrypsin values was observed: 12 of 46 patients after 30 days and 2 of 46 patients after 60 days. Weight increase after 2 months of gluten-free diet was significantly greater in patients with normal fecal chymotrypsin values at diagnosis than in patients with subnormal values, and a positive correlation was found between fecal chymotrypsin at diagnosis and weight increase (r = 0.56).. A small percentage of patients with celiac disease still had subnormal chymotrypsin concentrations after 60 days of gluten-free diet. Fecal chymotrypsin is a predictive index of weight recovery in the first months after diagnosis of celiac disease; it could be used to select patients for enzyme supplementation therapy.

Topics: Body Weight; Celiac Disease; Child; Child, Preschool; Chymotrypsin; Diet; Female; Glutens; Humans; Infant; Male; Pancreas

In 96 consecutive patients who underwent a 72-h faecal fat determination because of suspected nutrient malassimilation (maldigestion and/or malabsorption) faecal chymotrypsin (F-Chym) was estimated with a commercial photometric test (Monotest Chymotrypsin), comparing F-Chym concentrations in the first 24-h stool with the total 72-h F-Chym output. In the first 24-h faeces, the F-Chym concentration, calculated as a mean of three random samples, did not significantly differ from a single value obtained after homogenization. In known pancreatic disease, a F-Chym concentration less than 3.0 U/g wet faeces distinguished well between steatorrhoic patients (n = 12) and nonsteatorrhoic (n = 13) (positive predictive value (PV), 91%; negative PV, 86%) but was less suitable as a screening test for pancreatic steatorrhoea in the unselected patient group (positive PV, 61%; negative PV, 98%). Although the estimation of 72-h F-Chym output could differentiate between various subgroups of patients to a certain extent, the positive PV for discovery of pancreatic steatorrhoea in a single patient was low. Four patients had excessively high F-Chym output and increased bile acid excretion after ileal resection (n = 3) and radiation ileitis (n = 1), respectively, possibly indicating the removal of an inhibitory mechanism of pancreatic and biliary secretion in these conditions.

Topics: Adult; Celiac Disease; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Intestinal Diseases; Male; Middle Aged; Postgastrectomy Syndromes; Predictive Value of Tests; Sensitivity and Specificity; Weight Loss

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.

Topics: Adolescent; Celiac Disease; Ceruletide; Child; Child, Preschool; Chymotrypsin; Duodenum; Exocrine Pancreatic Insufficiency; Feces; Female; Glutens; Humans; Infant; Intestinal Mucosa; Male; Pancreas; Secretin

Histological material was studied in five unselected cases of intestinal large-cell non-Hodgkin's lymphoma, occurring in patients either with previously diagnosed coeliac disease, or with atrophic mucosa at the time of diagnosis. The morphological diagnosis in each case was centroblastic lymphoma: these tumours were composed of large cells with pale nuclei and prominent nucleoli. No phagocytosis was evident, but some cells showed considerable pleomorphism. Polykaryotic giant cells were infrequent. Immunohistochemical staining for lysozyme, alpha-1-anti-trypsin and alpha-1-anti-chymotrypsin failed to demonstrate any of these proteins in the tumour cells, although they were identified in accompanying reactive macrophages. There is thus no evidence for a histiocytic nature in these five cases. The tumours were immunoglobulin-negative. Again, polyclonal immunoglobulin could be demonstrated in reactive (plasma) cells in and near the tumour. The relevance of these immunological markers is discussed. We suggest that these tumours, and possibly some of those reported in a similar situation by other investigators, are in fact lymphocytic in origin. They are probably examples of centroblastic lymphoma, although T-cell lymphoma, rare in the gastrointestinal tract, cannot be ruled out by our immunohistological studies.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Celiac Disease; Cell Nucleolus; Cell Nucleus; Chymotrypsin; Histocytochemistry; Humans; Intestinal Neoplasms; Lymphocytes; Lymphoma; Macrophages; Male; Middle Aged; Muramidase; Plasma Cells

The coeliac active peptide B 3142, which has been isolated from a peptic-tryptic digest of gliadin and which consists of 53 amino-acid sequences, was partially hydrolyzed with alpha-chymotrypsin. The two fragment peptides CT-1 (positions 1-22 of B 3142) and CT-2 (positions 23-53) were separated by high-performance liquid chromatography on octadecyl silica gel and purified by gel filtration on Biogel P2. The examination in the organ-culture test including 18 coeliac patients on normal diet and 7 control persons have shown that the toxicity is preserved after the chymotryptic treatment and that the peptides B 3142, CT-1 and CT-2 do not significantly differ from one another according to their coeliac-specific effect.

Topics: Amino Acid Sequence; Celiac Disease; Chromatography, Gel; Chromatography, High Pressure Liquid; Chymotrypsin; Gliadin; Humans; Hydrolysis; Organ Culture Techniques; Peptide Fragments; Peptides; Plant Proteins

In 93 patients with known exocrine pancreatic function (secretin-pancreozymin test), NMR spectrometry and chloroform-methanol extraction of quantitatively collected, homogenized and lyophilized stools provided significantly correlated results with respect to stool fat concentration (r = 0.872) and total stool fat excretion/day (r = 0.983). In 83% of 24 patients with total stool fat excretion/day of more than 15 g (chloroform-methanol extraction), the indication for enzyme replacement was also established by stool fat concentrations of more than 35% determined by NMR spectrometry, irrespective of whether stool fat was measured in total stools or in 3 consecutive unhomogenized samples. In the remaining (17%) patients total stool fat excretion/day was only slightly elevated (16-21 g). Interestingly, in only 58% of patients actually needing enzyme replacement, did the secretin-pancreozymin test reveal a reduction of stimulated enzyme secretion to below 15% of the lower normal limit. The results indicate that NMR spectrometry of lyophilized samples of 3 consecutive unhomogenized stools is suitable for stool fat quantitation and for establishing the indication for enzyme replacement in chronic pancreatitis.

Topics: Amylases; Celiac Disease; Cholecystokinin; Chymotrypsin; Dietary Fats; Feces; Humans; Magnetic Resonance Spectroscopy; Pancreas; Pancreatitis; Secretin; Trypsin

The present study has been designed to work out the factors regulating the fasting serum levels of trypsin-like immunoreactivity in chronic pancreatitis. One hundred patients with chronic pancreatitis have been included and studied during a painless phase of the disease. No relationships have been observed between serum trypsin-like immunoreactivity and the presence of pancreatic calcifications. Serum immunoreactive trypsin levels showed a gradual decline parallel to the progressive impairment of bicarbonate and enzyme (trypsin and chymotrypsin) outputs in duodenal aspirates during pancreatic secretory studies. Therefore, serum trypsin-like immunoreactivity levels are thought to reflect the functional capacity of the exocrine pancreas. Reduced levels of trypsin-like immunoreactivity were detected in almost all patients with diabetes and steatorrhea. However, the finding of low levels also in a minority of chronic pancreatitis patients with normal endoscopic retrograde cholangiopancreatography or pancreatic secretory tests points to other factors which, in addition to the atrophy of the pancreatic parenchyma, may influence the circulating levels of trypsin-like immunoreactivity in chronic pancreatitis.

Topics: Antigens; Celiac Disease; Cholangiopancreatography, Endoscopic Retrograde; Chronic Disease; Chymotrypsin; Diabetes Complications; Humans; Pancreatitis; Trypsin

The diagnostic value of the fecal chymotrypsin test (FCT) was reevaluated with regard to (a) proved pancreatic hypofunction of different severity (183 pancreozymin-secretin tests); (b) the final clinical diagnosis, and (c) fecal fat excretion (208 patients with chronic pancreatitis; CP). Progressive pancreatic disease (cancer, CP) was mainly associated with moderate or severe pancreatic hypofunction (119/138; 86.2%) and a low incidence of false-normal FCT values (14/138; 10.1%). Miscellaneous disorders (mainly reversible pancreatic hypofunction) were mainly associated with slight pancreatic hypofunction and a high incidence of false-normal FCT values (17/45; 37.8%). Pancreatic steatorrhea (greater than 10 g/day) was found only in patients with markedly depressed FCT values. Progressive deterioration of pancreatic function was demonstrated by repeated FCT in CP (n = 220).

Topics: Celiac Disease; Cholecystokinin; Chronic Disease; Chymotrypsin; Exocrine Pancreatic Insufficiency; False Negative Reactions; Feces; Humans; Lipids; Pancreatic Function Tests; Pancreatitis; Secretin

Agarose gel electrophoresis (at pH 8.6) was used for qualitative determination of pancreatic enzymes in duodenal juice. The various enzymes were identified by staining techniques with specific chromogenic substrates, by quantitative determination of enzymes in eluates of gel slices, and by immunoelectrophoresis. The various protein bands corresponded to the following enzymes (from the anode to the cathode): chymotrypsin, trypsin, carboxypeptidase A, chymotrypsin, amylase (around the slit), lipase, elastase, and trypsin. The method was applied to a study of exocrine pancreatic function in 10 adults and 83 children suspected of having malabsorption. The duodenal juice, also analyzed for trypsin and amylase content, was collected in fasting condition and after a test meal of water. In patients with normal pancreatic function, all the enzyme bands were present and easy to recognize. In 87 patients carboxypeptidase A was present as two bands in 68 (80%), anodal trypsin as two bands in 39 (45%), and cathodal trypsin as two bands in 85 (97%). Electrophoresis of duodenal juice gave as much information from the fasting sample as after the test meal. Six children with pancreatic insufficiency (cystic fibrosis and Shwachmar's syndrome) had no or only faintly stained enzyme bands and a strongly stained albumin-containing band most anodally. The method is simple, rapid, and useful in routine work. The combination of this qualitative test with a quantitative one (e.g. trypsin determination) provides good information about exocrine pancreatic function.

Topics: Adolescent; Adult; Amylases; Carboxypeptidases; Celiac Disease; Child; Child, Preschool; Chymotrypsin; Duodenum; Electrophoresis; Electrophoresis, Agar Gel; Female; Food Hypersensitivity; Giardiasis; Humans; Immunoelectrophoresis; Infant; Malabsorption Syndromes; Male; Pancreatic Diseases; Pancreatic Elastase; Pancreatic Juice; Trypsin

The secretion of bicarbonate, lipase, and chymotrypsin into the duodenum in response to exogenous stimulation with secretin, 1 CU/kg-h, plus caerulein, 100 ng/kg-h, was investigated in 12 patients, on an average, 20.7 months after total gastrectomy and in 14 control subjects. The secretion of bicarbonate and lipase was significantly lower in patients than in controls. The reduction in outputs compared with the control values was 47.9%, 38.7%, and 24.2% respectively for bicarbonate, lipase, and chymotrypsin. Eight of the 12 patients (67%) had steatorrhoea. No significant correlation was found between this parameter and lipase output. It is concluded that the exocrine pancreatic function is impaired in the majority of patients subjected to total gastrectomy. The impairment, which particularly affects bicarbonate and lipase, is generally mild to moderate.

Topics: Adult; Aged; Bicarbonates; Celiac Disease; Chymotrypsin; Female; Gastrectomy; Humans; Lipase; Male; Middle Aged; Pancreas; Pancreatic Juice; Secretin; Secretory Rate

Topics: Adult; Amylases; Celiac Disease; Chymotrypsin; Digestion; Enzyme Therapy; Feces; Female; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Lipase; Male; Middle Aged; Pancreatin; Trypsin

I assayed 16 commercially available pancreatic extracts (representing capsules, tablets and enteric-coated tablets) for enzyme activities and the relation between the in vitro activities and in vivo potency evaluated in man. Lipase activity ranged from 10 to 3600 units per unit, with 11 preparations containing less than 600 units per unit. The preparations with the highest lipase activities were llozyme, 3600, Kuzyme HP, 2330, Festal, 2073, Cotazym, 2014, and Viokase, 1636 units. Lipase activity in vitro correlated with potency in vivo for tablets and capsules, with tablets and capsules being effective in reducing steatorrhea by 56.1 +/- 9 per cent and 48.6 +/- 10 per cent (mean +/- S.E.M.) respectively, P less than 0.001. Enteric-coated tablets were less effective (20 +/- 13 per cent reduction, P greater than 0.02). The longer the gastric pH remained greater than or equal to 4 (r = 0.915, P less than 0.01) and the higher the average duodenal pH (r = 0.966, P less than 0.01), the more marked the reduction in steatorrhea.

Topics: Administration, Oral; Biological Availability; Capsules; Celiac Disease; Chronic Disease; Chymotrypsin; Duodenum; Feces; Female; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Lipase; Male; Nitrogen; Pancreas; Pancreatic Diseases; Pancreatic Extracts; Pancreatic Juice; Tablets; Tablets, Enteric-Coated

Topics: Celiac Disease; Cholecystokinin; Chymotrypsin; Clinical Enzyme Tests; Fats; Feces; Humans; Lipid Metabolism; Lipids; Lymphatic System; Secretin; Vitamin A

Jos, J., Lenoir, G., de Ritis, G. & Rey, J. In vitro pathogenetic studies of coeliac disease. Effects of protein digests on coeliac intestinal biopsy specimens maintained in culture for 48 hours. Scand. J. Gastroent. 1975, 10, 121-128. Intestinal biopsies from controls and from children with treated or untreated coeliac disease were cultured for 48 hours in the presence or absence of various peptic-tryptic (P.T.) or peptic-tryptic-chymotryptic (P.T.C.) digests of gliadin and casein, using a modified organ culture method. In flat biopsy specimens obtained from children with active coeliac disease and maintained in culture in the presence of P.T. or P.T.C. digests of gliadin, whether autoclaved or not, a cytotoxic effect was obvious; but this effect was in part unspecific, since P.T. digests of casein were also slightly noxious in such experimental conditions. Biopsies from controls or from children with coeliac disease in remission were not affected by the presence in culture medium of casein or gliadin digests, whereas coeliac biopsies, also obtained from patients in remission but after gluten challenge, were specifically injured during culture with gliadin peptides. On the other hand, a thorough P.T.C. hydrolysis of gliadin abolished all its in vitro noxious effects, suggesting that its toxicity is related to a relatively large peptide.

Topics: Biopsy; Caseins; Celiac Disease; Child; Chymotrypsin; Culture Media; Culture Techniques; Duodenum; Epithelial Cells; Epithelium; Gastrointestinal Agents; Glutens; Humans; Intestinal Mucosa; Jejunum; Microscopy, Electron; Pepsin A; Plant Proteins; Time Factors; Trypsin

Topics: Adolescent; Adult; Body Height; Body Weight; Carboxypeptidases; Carotenoids; Celiac Disease; Child; Chymotrypsin; Cystic Fibrosis; Dietary Fats; Feces; Growth; Humans; Intestinal Secretions; Lipase; Lipids; Malabsorption Syndromes; Nitrogen; Nutritional Physiological Phenomena; Pancreatin; Prognosis; Trypsin; Xylose

Topics: Celiac Disease; Cholesterol; Chromium; Chymotrypsin; Expert Testimony; Feces; Follow-Up Studies; Humans; Intestinal Diseases; Lipoproteins; Male; Middle Aged; Occupational Diseases; Pancreas; Pancreatic Diseases; Trypsin

Topics: Body Weight; Celiac Disease; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Duodenum; Feces; Humans; Infant; Intestinal Diseases; Liver Diseases; Pancreas; Pancreatic Diseases; Time Factors

The material comprises 25 patients with gluten-induced enteropathy and 16 patients with various intestinal disorders. The intestinal contents were aspirated in four subsequent periods of 20 minutes each after ingestion of a standard meal. The volume, pH, and the concentration of alpha-amylase, trypsin, chymotrypsin, and lipase were determined in the collections. Only minor deviations from normal pH-levels were observed. In both groups of patients, the secretion of lipase, and to a minor degree that of amylase, were more markedly reduced than the secretion of the proteolytic enzymes. With the exception of the values of trypsin, concentrations of enzymes were seen to be below the lowest normal value in approximately one-third of the patients throughout the period of digestion. It is concluded that the pancreatic function was genuinely reduced in several patients with enterogenous malabsorption. It may be explained as an unspecific effect of the malabsorption.

Topics: alpha-Amylases; Celiac Disease; Chymotrypsin; Digestion; Duodenum; Enzymes; Female; Humans; Hydrogen-Ion Concentration; Intestinal Diseases; Lipase; Male; Pancreas; Trypsin

Topics: Celiac Disease; Chronic Disease; Chymotrypsin; Diagnosis, Differential; Feces; Glucose Tolerance Test; Humans; Internal Medicine; Pancreatic Diseases; Pancreatitis; Radiography

Topics: Adult; Celiac Disease; Chymotrypsin; Diagnosis, Differential; Feces; Humans; Pancreatitis; Trypsin