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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the mechanism by which pancreatic extract (PE) corrects the malabsorption of vitamin B12 in chronic pancreatic insufficiency (CPI), the following hypotheses were investigated: Firstly, PE might stimulate the absorption of vitamin B12 by changing the intestinal pH, secondly PE might stimulate the intestinal uptake of unbound vitamin B12, thirdly PE might abolish the inhibitory effect of vitamin B12 binders on the intestinal uptake of vitamin B12 bound to intrinsic factor (IF). PE had no effect on the pH in the small intestine and did not stimulate the uptake of unbound 57CoB12 by perfused rat intestinal segments. Preincubation of 57CoB12-IF with a non-IF B12-binder from human saliva (R-binder) reduced the uptake of 57CoB12 from 18.5 pg per cm intestine +/- 3.4 S.E.M. to 7.8 +/- 1.6 (p less than 0.02). PE abolished this inhibitory effect (p less than 0.05). The results indicate that PE corrects the malabsorption of vitamin B12 in CPI by an effect on non-IF B12- binders.
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PMID:Pancreatic extract and the intestinal uptake of vitamin B12. III. Stimulatory effect in the presence of a non-intrinsic factor vitamin B12 binder. 1 12

To assess the fate and efficacy of orally ingested enzymes in pancreatic insufficiency, we administered pancreatin to six patients by two schedules--eight tablets with a standard meal or two tablets hourly--and in six normal controls, quantified duodenal enzyme activity and related inactiviation of ingested enzymes to gastric and duodenal pH; in the six patients we measured malabsorption by fecal balance studies. Postprandially, gastric pH was similar in health and pancreatic insufficiency, and below 4 after 40 minutes. Duodenal pH in pancreatic insufficiency declined to approximately 4 beyond 100 minutes--lower than in health (P less than 0.05). Approximately 22 per cent and 8 per cent of trypsin and lipase activity ingested with either schedule was delivered to the ligament of Treitz. Prandial was as effective as hourly administration in decreasing steatorrhea and perhaps more effective in abolishing azotorrhea, and since it is also more convenient, we recommend it.
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PMID:Fate of orally ingested enzymes in pancreatic insufficiency. Comparison of two dosage schedules. 1 13

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

Phosphorylcholine and homocysteine have an important choleretic action and also potentiate exocrine pancreatic secretion by way of stimulation and a more effective preparation of the substrate against attack by lipolytic enzymes. The protection offered by pancreatic enzymes in the correction of the digestive insufficiency in the endoluminal stage is also known. An analysis was therefore made of the action of an association of phosphorylcholine homocysteine and digestive enzymes in cases of exocrine pancreatic insufficiency and primary or secondary malabsorption. This action was evaluated on the basis of the reduction of elimination of steatorrhoea. For this purpose, faecal lipids were determined with the method proposed by van de Kramer et al. The most significant results were obtained in cases where digestive insufficiency was most marked, where correction of the pancreatic enzyme deficiency and improved biliary function were particularly required.
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PMID:[Therapeutic effect of a pharmacologic combination of choleretics and digestive enzymes in exocrine pancreatic insufficiency]. 4 15

The concentration in serum of cathodal trypsinogen has been studied in certain clinical and experimental situations. The concentration correlated with pancreatic amylase activity. Low levels were found in patients with malabsorption due to exocrine pancreatic insufficiency. The concentration rose after endoscopic retrograde cholangiopancreatographic examinations (ERCP). After ERCP, however, no trypsin was detected complexed with protease inhibitors, as is generally found in acute pancreatitis. The trypsinogen concentration in serum also rose in renal failure indicating a renal elimination route for the endogenous trypsinogen.
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PMID:Studies on the turnover of endogenous cathodal trypsinogen in man. 10 10

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

The failure of standard oral pancreatic enzyme replacement therapy to correct malabsorption in patients with advanced pancreatic insufficiency is likely due to acid-peptic inactivation of ingested enzymes. Theoretically, the use of cimetidine, an H2-receptor antagonist, in conjunction with oral enzymes, would permit greater transgastric passage of ingested enzymes with resulting improvement in intraluminal lipolysis. To test this hypothesis, we studied the effects of orally administered cimetidine in two groups of patients by utilizing a previously validated double-marker perfusion technique. Cimetidine, in varying doses, had no effect on postprandial exocrine pancreatic function in 16 duodenal ulcer patients without pancreatic disease. In six patients with pancreatic insufficiency, cimetidine produced a pronounced decrease in the output of gastric acid and secretory volume, resulting in reduction of postprandial acidity and intragastric volume. These actions of cimetidine should retard or prevent inactivation of ingested enzymes and also increase their intragastric concentration, with resulting enhancement of luminal duodenal enzyme activity. Supplemental cimetidine may thus be useful in the medical management of patients who fail to respond to routine pancreatic extract therapy alone.
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PMID:Rationale for the use of cimetidine in pancreatic insufficiency. 34 Aug 5

Human bile incubated with vitamin B12 bound to intrinsic factor in human gastric juice will effectively dissociate this complex, and the vitamin will transfer to non-intrinsic factor unsaturated binding protein(s) contained in bile. Preincubation of the bile with pancreatic enzymes, particularly trypsin, and pepsin, decreases this effect of bile on the intrinsic factor--vitamin B12 complex by digesting the unsaturated binder(s) in the bile. These studies help explain why there is malabsorption of tracer amounts of vitamin B12 in some patients with pancreatic insufficiency, and why this abnormality is correctable by the administration of pancreatic extract.
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PMID:Dissociation of the intrinsic factor--vitamin B12 complex by bile: contributing factor to B12 malabsorption in pancreatic insufficiency. 38 77

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

Malabsorption of bile acids is known to occur in patients with pancreatic insufficiency particularly when due to cystic fibrosis. Abnormal biliary secretion or intraluminal acidic precipitation of bile acids could contribute to the steatorrhea of pancreatic insufficiency. To measure bile acid outputs and duodenal concentrations of bile salts and lipids simultaneously, we performed intestinal intubation and perfusion studies during feeding of a solid test meal in 6 healthy controls and 8 adult patients with advanced acquired exocrine pancreatic insufficiency. The effects of various treatment regimens were also investigated. Postprandial bile acid secretion was similar in all treatment groups. However, significant (P less than 0.05) reductions in micellar concentrations of bile acids and fatty acids were observed in untreated pancreatic insufficiency. These abnormalities were directly related to pH-induced precipitation of bile acids and were corrected only by the addition of cimetidine to standard pancreatin therapy. Thus, in pancreatic insufficiency, treatment with pancreatin plus cimetidine enhances fat digestion and absorption by reducing both acid-peptic inactivation of lipase and acidic precipitation of bile acids.
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PMID:Reduced intraluminal bile acid concentrations and fat maldigestion in pancreatic insufficiency: correction by treatment. 44 41


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