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

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

AIDS-associated gastric secretory failure has been characterized by decreased secretion of acid, pepsin, and gastric juice volume. To determine whether decreased intrinsic factor secretion and vitamin B12 malabsorption occur in this entity, we performed prospective measurements of maximal acid output, intrinsic factor output, vitamin B12 absorption, serum vitamin B12, and holotranscobalamin II in 10 consecutive AIDS patients. Four of 10 patients had low maximal acid output, i.e., < or = 1.5 mEq/h (control = 12.8 +/- 9.0, range 2.5-25 mEq/h). Four patients had low intrinsic factor output, i.e., < or = 1.1 microgram/h (control = 8.2 +/- 6.9, range 3.1-19.4 micrograms/h). One patient with low intrinsic factor output had low serum vitamin B12 and a Schilling test consistent with pernicious anemia. A second patient with very low intrinsic factor output (0.16 micrograms/h) had low parts I and II Schilling tests; malabsorption most likely resulted from both low intrinsic factor secretion and ileal disease. One of three vitamin B12 malabsorbing patients, with normal serum vitamin B12, had low holotranscobalamin II, 25 pg/ml (control holotranscobalamin II = 76 +/- 44, range 44-152 pg/ml). Maximal acid output and intrinsic factor output did not correlate in AIDS (r = 0.36, p = 0.30) in contrast to the expected correlation in controls (r = 0.91, p = 0.03). We conclude that low intrinsic factor secretion is common in AIDS and contributes to vitamin B12 malabsorption. Decreased parietal cell secretion of intrinsic factor and acid may occur independently in human immunodeficiency virus-associated gastric secretory failure. Low holotranscobalamin II, an early manifestation of vitamin B12 malabsorption, results in decreased delivery to vitamin B12-dependent tissues prior to depletion of serum vitamin B12. Regular supplementation with vitamin B12 may therefore be warranted in patients with advanced HIV infection.
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PMID:Decreased intrinsic factor secretion in AIDS: relation to parietal cell acid secretory capacity and vitamin B12 malabsorption. 144 41

Three siblings presented in their second year of life with megaloblastic anemia that responded to parenteral cobalamin (Cbl). Schilling tests were less than 1%, correcting to 5 to 15% after addition of hog intrinsic factor (IF). Gastric acid analysis and gastric biopsies were normal by light and electron microscopy. Gastric juice contained less than 3 pmol/ml of Cbl-binding ability due to IF (normal, 10-34 pmol/ml) and less than 2 pmol/ml of IF when measured with a radioimmunoassay (RIA) using normal human IF-[57Co]Cbl and rabbit anti-human IF serum (normal, 17-66 pmol/ml). However, RIA employing rabbit anti-hog IF serum gave values of 4-13 pmol/ml of IF (normal, 11-33 pmol/ml). This material had an apparent molecular weight of 40,000 (normal IF = 70,000). The IF from gastric biopsies appeared normal in terms of Cbl-binding ability, ileal binding, molecular weight, and both RIAs. This IF differed from normal mucosal IF, in that it lost its Cbl-binding ability when incubated at 37 degrees C at acid pH or in the presence of pepsin or trypsin. This loss was retarded when [57Co]Cbl was bound to the IF before these incubations. The stabilizing effects of neutralization and Cbl were also demonstrated in vivo. Schilling tests for the siblings of 0.4, 0.5, and 1.0% increased to 2.7, 5.7, and 4.3% (P less than 0.05), respectively, when the Schilling tests were repeated with the addition of NaHCO3 and cobinamide (which allows Cbl to bind immediately to IF). We conclude that Cbl malabsorption in these children is due to an abnormal IF that is markedly susceptible to acid and proteolytic enzymes which cause a decrease in its molecular weight and Cbl-binding ability and a loss of antigenic determinants that are recognized by the anti-human IF serum.
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PMID:Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis. 390 80

The suppressive effects of cimetidine on acid, pepsin, and intrinsic factor secretion have been well documented; however, the effect of cimetidine on cobalamin absorption has not been assessed. The absorption of both unbound [57Co]cyanocobalamin and protein-bound [57Co]cyanocobalamin was evaluated in 12 patients with duodenal ulcer disease during and after discontinuation of cimetidine therapy. Cimetidine administration did not lead to malabsorption of unbound cobalamin but caused malabsorption of protein-bound cobalamin (0.22 +/- 0.08%, [mean +/- 1 SEM] versus 2.3 +/- 0.10% in control subjects, P less than 0.01). This malabsorption was reversible upon discontinuation of cimetidine. Patients on cimetidine therapy malabsorb protein-bound cobalamin and, during long-term treatment, are at risk for developing cobalamin deficiency. This malabsorption was reversible upon discontinuation of cimetidine. Patients on cimetidine therapy malabsorb protein-bound cobalamin and, during long-term treatment, are at risk for developing cobalamin deficiency. This malabsorption of protein-bound cobalamin is not detectable by the usual tests of cobalamin absorption which employ unbound cobalamin.
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PMID:Malabsorption of protein-bound cobalamin but not unbound cobalamin during cimetidine administration. 676 34

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

Food-cobalamin malabsorption is marked by the inability to release cobalamin from food, which therefore cannot be taken up by intrinsic factor for absorption. The defect is not detectable by classical clinical tests like the Schilling test which are all based on the absorption of free, crystalline cobalamin. Tests of food-cobalamin absorption have been devised, the most popular ones using cobalamin bound to eggs or to chicken serum. The disparity between the abnormal results of these tests and the normal results with the Schilling test defines the disorder of food-cobalamin malabsorption. Release of cobalamin from food requires acid and pepsin, and most food-cobalamin malabsorptive states can be traced to gastric defects. However, other mechanisms may also play a role. The malabsorption is limited to food cobalamin and any free cobalamin, presumably including recycled biliary cobalamin, will be absorbed normally, which may explain its frequently insidious nature. The effect on cobalamin status covers a broad spectrum. At one extreme, some individuals, perhaps in the earliest stages, have normal cobalamin status, while at the other extreme may be found deficiency every bit as severe as in the most florid case of pernicious anaemia. Most often, however, the deficiency is mild, frequently marked by only a low serum cobalamin level, mild evidence of metabolic insufficiency and, sometimes, minimal clinical sequelae. Moreover, in some cases the gastric defect progresses and intrinsic factor secretion is affected, thus transforming into classical pernicious anaemia; this is not inevitable, however, and probably occurs in only a minority of patients. The course of food-cobalamin malabsorption is therefore a varied one. Nevertheless, it may be the most common cause of subtle or mild cobalamin deficiency and it is also sometimes associated with severe deficiency. Its identification and treatment need to be considered more widely in the clinical setting.
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PMID:Malabsorption of food cobalamin. 853 65

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

In response to research findings that 10% to 30% of people aged 51 years and older may have protein-bound vitamin B-12 malabsorption, the National Academy of Sciences' Institute of Medicine recommends that these people consume a majority of the new Recommended Dietary Allowance (RDA) of 2.4 micrograms/day in its synthetic form rather than in its food form. Protein-bound vitamin B-12 malabsorption in older adults has been attributed to reduced pepsin activity and gastric acid secretion, which interfere with cleavage of vitamin B-12 from dietary protein before absorption. Unlike patients with pernicious anemia, most people with protein-bound vitamin B-12 malabsorption produce intrinsic factor and have the ability to absorb synthetic vitamin B-12 normally. Early diagnosis is necessary to prevent the untoward effects of vitamin B-12 deficiency. A thorough assessment of vitamin B-12 status entails measurement of multiple biochemical assessment indexes, including serum vitamin B-12, methylmalonic acid, and homocysteine concentrations. Dietitians and other health care professionals should be aware of the prevalence of vitamin B-12 deficiency in older adults and be familiar with sources of synthetic vitamin B-12 to facilitate implementation of the new RDA.
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PMID:Practitioners' guide to meeting the vitamin B-12 recommended dietary allowance for people aged 51 years and older. 1036 36

Yarrowia lipolytica lipase has been assumed to be a good candidate for the treatment of fat malabsorption in patients with pancreatic insufficiency. Nevertheless, no systematic studies on its stability under physiological conditions pertaining to the human GI (gastrointestinal) tract have been published. Stability of various Y. lipolytica lipase powder formulations at various physiological pH values as well as the effect of digestive proteases and bile salts on enzyme activity were investigated. Results were compared with those obtained from another competing fungal lipase sourced from Candida rugosa. Among the studied formulations, Y. lipolytica lipase stabilized with gum arabic and skimmed milk powder was the most promising powder formulation. Under acidic conditions (pH 3-5), this formulation showed higher stability than those observed with the other Y. lipolytica lipase formulations and C. rugosa lipase. In addition, in the presence of gum arabic and skimmed milk powder as additives, Y. lipolytica lipase exhibited markedly higher resistance to pepsin, trypsin and chymotrypsin actions. Resistance to proteolytic degradation by digestive proteases was also by far higher than that observed with C. rugosa lipase. Similar behaviour was, however, observed when these two fungal lipases were incubated with increased concentrations of bile salts. Residual lipase activity of both fungal lipases showed a slight decrease in NaTDC (sodium taurodeoxycholate) concentration above 4 mM. Consequently, Y. lipolytica lipase formulated with gum arabic and milk powder seemed to have great potential for use as a therapeutic tool for patients with pancreatic insufficiency.
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PMID:A highly stable Yarrowia lipolytica lipase formulation for the treatment of pancreatic exocrine insufficiency. 2095 63