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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

Pepsin had no effect on the vitamin B12 binder in human saliva (R-binder), while trypsin was found to reduce the apparent molecular weight of the R-binder and to release vitamin B12 from the R-B12complex of human saliva and human gastric juice (HGJ). Trypsin had no effect on the molecular weight and biological activity of intrinsic factor (IF) in HGJ, as demonstrated by gel filtration on Sephadex G-150 and the uptake of IF-B12 by guinea pig intestinal brush borders. An extract of purified guinea pig intestinal lysosomes was also without effect on the molecular weight and the biological activity of IF but was found to release vitamin B12 from the R-B12 complex. The results support the observation that the external pancreatic secretion corrects malabsorption of vitamin B12 by an effect on the non-IF protein in the intestinal juice. Moreover, the results indicate that lysosomal enzymes are not involved in the intestinal absorption of vitamin B12.
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PMID:The effect of proteolytic enzymes on the vitamin B12-binding proteins of human gastric juice and saliva. 12

Food-cobalamin absorption depends on the initial release of cobalamin from its binders in food. Therefore, the characterization of patients' gastric juices and their behavior in this process was undertaken. Pentagastrin-stimulated gastric juice specimens from three patients with severe food-cobalamin malabsorption, six patients with mild malabsorption, and five patients with normal absorption were tested for pH, pepsin, intrinsic factor content, and an in vitro method that quantitates transfer of cobalamin from egg yolk to gastric R binder. Transfer of cobalamin correlated best with in vivo egg yolk-cobalamin absorption test results in the 14 patients (r = 0.731, P < 0.005). Transfer also correlated inversely with gastric juice pH (r = -0.619, P < 0.02). Basal gastric juice specimens, with their higher pH, from the same subjects failed to promote cobalamin transfer until their pH was lowered to 1.0-1.3. Pepsin levels did not correlate with in vitro transfer or with absorption in vivo; nevertheless, raising the low pepsin concentration of one stimulated gastric juice improved transfer, while inhibiting pepsin activity with pepstatin A inhibited transfer. Mixing experiments with selected stimulated gastric juices demonstrated that poor in vitro transfer, which in a few cases seemed unrelated to pH or pepsin levels, was not due to any inhibitory activity of such gastric juices. These studies confirm that gastric acid and pepsin play a central role in releasing food-bound cobalamin and transferring it to R binder, but suggest that other, still unidentified gastric defects occasionally contribute to impaired transfer; the latter defects are not inhibitory in nature but seem to involve the absence of a permissive activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro studies of gastric juice in patients with food-cobalamin malabsorption. 799 73

In vitro experiments were conducted to characterize the activity and the stability of lipase from animal (crude porcine, CPL; lyophilized porcine, LPL), fungal (Rhizopus arrhizus, RAL; Aspergillus niger, ANL), and bacterial (two Pseudomonas spp., PL1, PL2; and Chromobacterium viscosum, CVL) sources when exposed to conditions associated with the glandular stomach. Activity was measured at pH 3 to 8, 40 C and then monitored in response to temperature (40 C), time of exposure (0 and 30 min), pH (3 and 7), and pepsin level (5, 50, and 500 U/mL). All lipases except ANL and CVL had maximum activity at pH 7 to 8. The optimal pH for ANL and CVL were 5 and 6 to 8, respectively. Exposure of lipases to 40 C and pH 7 for 30 min reduced the activity of all lipases except ANL. In contrast, 40 C increased ANL activity 2.5-fold. Although activity of all lipases was reduced by exposure to pH 3, it was nearly eliminated for CPL and LPL. Pepsin concentration had only minor effects on lipase activity and then only at high concentration. The results demonstrate that bacterial lipases (PL1, PL2, and CVL) and ANL are more stable under conditions that approximate the glandular stomach and may explain why dietary porcine lipase has been ineffective in preventing fat malabsorption in previous in vivo studies.
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PMID:Stability of porcine and microbial lipases to conditions that approximate the proventriculus of young birds. 983 41

A number of clinical conditions are caused by disorders affecting the mucosal lining of the gastrointestinal tract. Some patients suffer from a loss of mucosal surface area due to congenital defects or due to surgical resections ("short bowel syndrome"). Other patients have inborn or acquired defects of certain mucosal functions (e.g., glucose-galactose malabsorption, bile acid malabsorption). Many patients with these mucosal disorders could be more effectively treated if healthy mucosa were available in larger quantities as a replacement or functional supplement. We therefore developed methods to transplant mucosal stem cells from one part of the intestine to another and to make bioengineered intestinal mucosa. We generated an animal model of bile acid malabsorption using rats that underwent resection of the distal 25% of their small intestine (ileum). This resulted in significant losses of bile acids with the fecal excretions in these animals. We subsequently harvested ileal stem cell clusters from neonatal donors, removed the mucosa from a segment of proximal intestine (jejunum), and implanted the stem cell clusters into the debrided segment of jejunum. After four weeks, the animals had developed a functional "neomucosa." We inserted the "neo-ileal" segment into continuity as a substitute ileum. Postoperative measurements of fecal bile acid excretion showed that we were able to reverse the malabsorption syndrome in this model. This was the first reported neo-mucosa-based treatment of a malabsorption syndrome in vivo. We subsequently studied different biodegradable PGA and PLLA scaffoldings to generate bioengineered intestinal mucosa. We implanted these materials into omentum of rats and were able to identify a PGA/PLLA hybrid material on which engraftment rates of 36% of the available surface area could be achieved. Most recently, we developed a novel technique that permits direct observation of cell-biomaterial interactions after implantation into omentum or intestine in vivo. This method will help to optimize engraftment conditions for stem cell clusters on biomaterials.
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PMID:To make a new intestinal mucosa. 1660 91