Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cobalamin (Cbl; vitamin B(12)) malabsorption in pancreatic insufficiency can be partially corrected by bicarbonate and completely corrected by pancreatic proteases but the mechanisms involved are unknown. Because saliva contains enough R-type Cbl-binding protein (R protein) to bind all of the dietary and biliary Cbl, it is possible that R protein acts as an inhibitor of Cbl absorption and that pancreatic proteases are required to alter R protein and prevent such inhibition. To test this hypothesis we studied the ability of R protein and intrinsic factor (IF) to compete for Cbl binding and ability of pancreatic proteases to alter this competition. Human salivary R protein bound Cbl with affinities that were 50- and 3-fold higher than those of human IF at pH 2 and 8, respectively. Cbl bound to IF was transferred to an equal amount of R protein with t((1/2))'s of 2 and 90 min at pH 2 and 8, respectively, and within several hours respective ratios of R protein-Cbl/IF-Cbl of 50 and 2 were observed. Cbl bound to R protein was not transferred to IF at either pH 2 or 8. Incubation of R protein with pancreatic proteases at pH 8 led to a 150-fold decrease in its affinity for Cbl. Incubation of R protein-Cbl with pancreatic proteases led to complete transfer of Cbl to IF within 10 min. Gel filtration studies with R protein-[(57)Co]Cbl and (125)I-R protein showed that pancreatic proteases partially degraded R protein. Pancreatic proteases differed in their ability to effect these changes with trypsin > chymotrypsin > elastase. Pancreatic proteases did not alter IF in any of the parameters mentioned above. Pepsin failed to alter either R protein or IF. THESE STUDIES SUGGEST THE FOLLOWING: (a) that Cbl is bound almost exclusively to R protein in the acid milieu of the stomach, rather than to IF as has been assumed previously; (b) that Cbl remains bound to R protein in the slightly alkaline environment of the intestine until pancreatic proteases partially degrade R protein and enable Cbl to become bound exclusively to IF; and (c) that the primary defect in Cbl absorption in pancreatic insufficiency is a lack of pancreatic proteases and a failure to alter R protein and effect the transfer of Cbl to IF. These studies also suggest that the partial correction of Cbl malabsorption observed with bicarbonate is due to neutralization of gastric HCl, since at slightly alkaline, pH IF can partially compete with R protein for the initial binding and retention of Cbl.
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PMID:Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency. 2 56

Crude preparations of hog gastric intrinsic factor or their own previously collected gastric juices administered with labeled vitamin B12 did not enhance vitamin B12 absorption in patients with vitamin B12 malabsorption secondary to pancreatic insufficiency. However, when these sources of gastric intrinsic factor were incubated with three times crystallized preparations of insolubilized bovine trypsin or chymotrypsin, the proteolytic enzymes were removed by centrifugation, and the preparations of gastric intrinsic factor were readministered to these patients, the absorption of vitamin B12 was markedly enhanced. Studies of hog gastric intrinsic factor before and after exposure to proteolytic enzymes failed to show any difference on Sephadex chromatography or polyacrylamide gel electrophoresis or on its affinity for vitamin B12 or the ileal receptor in guinea pigs. These investigations demonstrate that: (1) gastric intrinsic factor as secreted by subjects with pancreatic insufficiency or obtained from hog pyloric mucosal extracts is ineffective in promoting vitamin B12 absorption in patients with pancreatic insufficiency, (2) incubation of crude preparations of gastric intrinsic factor with insolubilized pancreatic proteases modified these preparations of gastric intrinsic factor in an as yet undefined manner, allowing them to enhance vitamin B12 absorption, and (3) in vitro studies using gut sacs or brush border preparations do not reflect the abnormality in vitamin B12 absorption associated with pancreatic dysfunction.
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PMID:Evidence that pancreatic proteases enhance vitamin B12 absorption by acting on curde preparations of hog gastric intrinsic factor and human gastric juice. 31 82

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.
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PMID:Agarose gel electrophoresis of duodenal juice in normal condition and in children with malabsorption. 43 37

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.
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PMID:Determination of faecal chymotrypsin concentration and 72-hour faecal chymotrypsin output in the detection of pancreatic steatorrhoea. 177 36

This study compares the diagnostic utility of fecal chymotrypsin (CT) output in timed stool collections and random stools using a new photometric enzyme assay. The CT output (mean +/- SD, U/24 h) was 1,487 +/- 1,980 in 127 children with normal fat absorption and negative sweat-chloride test (mean age 45 months), and 1,804 +/- 1,452 in 27 cases with fat malabsorption due to nonpancreatic disease (mean age 41 months). 66 cases of cystic fibrosis (CF) were examined (mean age 119 months). Stool output in 19 newly diagnosed patients before therapy was 85 +/- 94, in 42 patients receiving enzyme replacement therapy was 3,462 +/- 2,841, and in 5 patients with pancreatic sufficiency 1,754 +/- 1,482. Using nonparametric statistics, 120 U/24 h was defined as the lower limit of the 95-percentile for stool CT output. Only 5 of the 127 patients with normal fat absorption had output below that limit. None of the patients with nonpancreatic malabsorption and only 1 treated CF patient had lower values. Sixteen of the newly diagnosed CF patients had stool CT less than 120 U/24 h. The sensitivity of the test is therefore 84% and its specificity 97% at this decision threshold. However, no diagnostic advantage is gained from measuring CT output in timed stool collections as compared to random stools.
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PMID:Is chymotrypsin output a better diagnostic index than the measurement of chymotrypsin in random stool? 339 Nov 58

Simultaneous measurements of duodenal and faecal chymotrypsin were made in 30 children aged 3 weeks to 14 years. Apparent chymotrypsin secretion rates measured after stimulation with pancreozymin were compared with the mean faecal chymotrypsin concentration derived from three stool specimens collected at random within 72 hours of the intraduodenal test. In the 25 children who responded to pancreozymin stimulation the mean faecal chymotrypsin concentration was significantly positively correlated with the apparent chymotrypsin secretion rate. Correlation using single specimen stools collected at random was appreciably poorer. In the five children with undetectable or only traces of chymotrypsin in the duodenum after stimulation, the mean faecal chymotrypsin concentrations were only 3-10% of the lower limit of the reference interval. In a second group of 46 children with cystic fibrosis proved by sweat tests and clinical evidence of malabsorption, the chymotrypsin concentration measured in a single stool specimen collected at random was unequivocally subnormal in each case. Faecal chymotrypsin measurement is a rapid, simple, cheap, readily repeated, non-invasive test of high specificity and sensitivity. Faecal chymotrypsin should be measured before contemplating intraduodenal tests of pancreatic function.
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PMID:Faecal chymotrypsin: a reliable index of exocrine pancreatic function. 341 94

The fecal chymotrypsin (FC) levels in samples collected over 24 h were determined by a new commercial colorimetric method from Boehringer Mannheim in 82 children suffering from various pancreatic disorders. The patients were divided into 4 groups, in accordance with the following etiologies: cystic fibrosis of the pancreas (CFP), chronic severe hepatic disorders (CSH), primary malabsorption syndrome (PMS) and malnutrition due to nondigestive causes (M). The control group comprised 48 children of similar ages. The 24th FC levels as U/g (mean +/- SD) were: 34 +/- 6 in the control group, 2 +/- 2 in the CFP group, 15 +/- 6 in the M group, 19 +/- 9 in the CSH group and 43 +/- 13 in the PMS group. The differences between the CFP patients and all the other groups were statistically significant. These results indicate that the FC levels may be suitable as a diagnostic indication of CFP and capable of differentiating between this disorder and other causes of pancreatic insufficiency.
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PMID:Fecal chymotrypsin levels in children with pancreatic insufficiency. 358 67

As aflatoxin causes malabsorption and its toxicity is enhanced by a low protein diet, digestive enzymes formed in the pancreas apparently are influenced by aflatoxin. This hypothesis was investigated in a 2 X 2 factorial experiment. Six groups of 10 egg-type chickens per treatment were analyzed for the absence and presence of aflatoxin (0 and 4 micrograms/g diet) and for normal (12.75%) and low (10.00%) protein in soy-dextrose diets. The specific activities of pancreatic chymotrypsin, amylase, and lipase, but not trypsin, were increased significantly (P less than .01) by aflatoxin. Lowering dietary protein had no effect by itself except to increase amylase activity. Low protein and aflatoxin interacted to lessen but not prevent the effect of aflatoxin on chymotrypsin and amylase. Calculation of total pancreatic activities revealed that aflatoxin increased trypsin, chymotrypsin, amylase, and lipase to 107, 169, 113, and 119%, respectively, of control values on the low protein diet, whereas values were 99, 175, 115, and 115%, respectively, on the normal protein diet. Neither aflatoxin nor low protein altered significantly (P less than .05) the lipid content of fecal material. Thus, aflatoxicosis in egg-type chickens is characterized by a surplus of some digestive enzymes and by normal fecal lipids in contrast to the specific deficiency of amylase and lipase and steatorrhea reported earlier in meat-type chickens. Whereas malabsorption caused by aflatoxin in broilers can be accounted for in part by impaired digestion, this mechanism apparently does not occur in egg-type chickens.
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PMID:Enhanced production of pancreatic digestive enzymes during aflatoxicosis in egg-type chickens. 361 25

To establish the diagnosis of acute pancreatitis the estimation of amylase in serum and urine, lipase and radio-immunoreactive trypsin in the serum are useful. Lipase estimations are more helpful than measuring amylase values. Trypsin-RIA-tests are increasingly important adults. But in chronic pancreatitis and inborn secretory insufficiencies of the pancreas these methods are less helpful. PABA-test, pancreolauryl-test (PLT), and the estimation of chymotrypsin in faeces are screening procedures, although their results correlate well amongst each other. As compared to the chymotrypsin estimation in faeces PABA test and PLT allow for some semiquantitative estimation of the secretory function and dynamics of the gland. The influence of malabsorption, liver and kidney diseases on these parameters is not yet quite clarified. Besides screening they are undoubtedly of value for judging the course and therapy of cystic fibrosis, Shwachman-syndrome, iatrogenic lesions by cytostatics (immunosuppressives and corticosteroids). Quantitative estimations of fat in faces and the pancreozymin test are no longer of significance.
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PMID:[Examination of pancreatic function in children with special reference to the PABA-test (author's transl)]. 616 2

In many ways diagnosis of pancreatic disorders in children is difficult. Since pancreatic parameters are age-dependent, reliable laboratory parameters are not easily established. Children are less likely than adults to endure tolerance tests and invasive test methods should therefore be used only in special situations. Estimation of chymotrypsin in faeces seems to be an earlier indicator of pancreatic insufficiency than the PABA-peptide-test. A secretin-pancreozymin test can only be advised for first diagnosis after screening has repeatedly indicated pathological values and malabsorption has more or less been ruled out. A threefold rise in serum amylase values - matched for age - suggests pancreatitis and sonography should then be applied to obtain further clarification.
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PMID:[Diagnosis of pancreatic diseases in childhood (author's transl)]. 616 3


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