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)

In juvenile X-linked hypophosphatemic (Hyp) mice, whole body calcium balances are significantly lower than in genetically normal mice. This is associated with low duodenal vitamin D-dependent calcium-binding protein and a failure of skeletal mineralization. To seek more specific evidence of an intestinal defect in these mice, absorption of 45Ca was measured in isolated duodenal segments in vivo in mice from 2-13 weeks of age. The duodenum was isolated by sutures and 45Ca was injected into the lumen in 150 mM NaCl and 2 mM CaCl2 at pH = 7.2. Absorption was measured by the amount of isotope remaining in the lumen and by the plasma isotope level. Hemizygous Hyp male and heterozygous Hyp female mice absorbed significantly less 45Ca at 4 and 7 weeks of age than genetically normal mice while Hyp mice at 2, 10, and 13 weeks of age were not significantly affected. At 4 and 7 weeks of age, the Hyp mice also had significantly reduced plasma radioactivity midway through the collection period as well as at the end of the period. To explore a possible mechanism for this malabsorption, 1,25(OH)2-vitamin D receptors were measured in cytosol prepared from 4-week-old normal and Hyp duodenum. There were non-significant differences between the normal and Hyp mice in both binding affinity, Kd, and the number of receptors, nmax. In conclusion, juvenile Hyp mice at 4 and 7 weeks of ages malabsorbed calcium from their duodenum. Hyp mice younger than this period were not affected nor were adult Hyp mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced absorption of 45calcium from isolated duodenal segments in vivo in juvenile but not adult X-linked hypophosphatemic mice. 300 89

Intracellular Ca++ is known to influence Na+ flux in luminal membranes. Abnormally elevated Ca++ levels in some cells is believed to be the primary pathophysiologic defect in cystic fibrosis (CF). This in turn is thought to alter Na+ transport which accounts for certain clinical manifestations of this disease. Two Na+-dependent intestinal transport mechanisms have been reported to be suppressed or missing in CF. To examine whether alterations in cell Ca++ may account for these findings, studies were performed to examine the influence of Ca++ on Na+-solute co-transport across intestinal luminal membranes. Purified brush border membrane vesicles prepared from rat small bowel were preincubated in either Ca++-free buffer or buffer containing 2.5 mM CaCl2. Ca++ loaded vesicles showed marked inhibition of Na+ co-transport of taurocholic acid, taurochenodeoxycholic acid, glucose and valine when compared to controls. The uptake of Na+ was also significantly reduced by intravesicular Ca++. These data demonstrate that intravesicular Ca++ inhibits Na+-coupled solute transport as well as Na+ influx across intestinal brush border membranes. These data suggest that intracellular Ca++ may suppress Na+-dependent solute absorption in the intestine. Results presented here further support the theory that elevated intracellular Ca++ may account for intestinal malabsorption and other altered transport phenomena reported in CF.
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PMID:Inhibition of Na+-coupled solute transport by calcium in brush border membrane vesicles. 648 64

X-linked hypophosphatemia, a common metabolic bone disease in humans and mice (the Hyp and Gy mutations), is characterized by decreased plasma phosphate, decreased renal tubular reabsorption of phosphate, rickets, and osteomalacia. The question of whether intestinal malabsorption of calcium contributes to the bone disease is controversial. Intestinal absorption of 45Ca was studied in three different mouse colonies: Gy on B6C3H background, Hyp on B6C3H background, and Hyp on C57BL/6J background, all at 4 weeks of age. The duodenum was isolated by sutures, and 45Ca in a 150 mM NaCl and 2 mM CaCl2 solution at pH 7.2 was injected into the lumen. Absorption was measured by the amount of 45Ca remaining in the lumen and by the plasma isotope level. The Gy and Hyp mice of both sexes significantly malabsorbed 45Ca at 4 weeks of age compared to normal littermates. Following the 4 week study, intestinal absorption was measured at 2, 7-8, and 12 weeks of age in normal and Gy mice on the B6C3H background. At 2 and 7-8 weeks of age, the Gy males significantly malabsorbed 45Ca compared to their normal littermates. Serum 1,25-dihydroxyvitamin D was not significantly altered in Gy males at 4 weeks of age. This suggests the possibility of resistance of the intestine to stimulation. Malabsorption of calcium in young Gy and Hyp mice may exacerbate the low mineralization in their rachitic bone disease.
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PMID:Intestinal malabsorption of 45calcium in young Gy mice, a second model for X-linked hypophosphatemia. 826 20