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 order to assess the usefulness of intestinal biopsies as indicators of end-organ responsiveness to vitamin D in uremic patients, calcium binding activity and calcium binding protein (CaBP) content were measured in intestinal biopsies from 12 uremic patients (glomerular filtration rate less than 5.0 ml/min) and 12 adult controls. Values for both were found to vary with the site of biopsy, highest values being obtained in the duodenal bulb, with lower values distally. Values for activity correlated with values for CaBP content in both normals and uremics and no difference was observed between groups. Levels of calcium binding activity and content of CaBP did not correlate with serum immunoreactive parathormone levels, but were directly related to circulating 25-hydroxycholecalciferol (25-OHD) levels. The data show that intestinal CaBP is normal in activity, quantity, and affinity for calcium in malabsorbing uremic patients, and are consistent with the hypothesis that calcium malabsorption in uremia is unrelated to deficiency of intestinal calcium binding protein.
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PMID:Intestinal calcium binding protein in uremia. 11 81

The intestinal absorption of calcium is often depressed in patients with chronic renal insufficiency. Furthermore, the malabsorption of calcium and the osteodystrophy which occur in association with chronic renal disease are often "resistant" to vitamin D; the basis for this resistance remains uncertain however. Recent studies by others have emphasized the role of an abnormality in the metabolism of vitamin D in accounting for the alterations in the calcium absorption and the apparent vitamin D-resistance which accompany the uremic syndrome. The present studies with an experimentally uremic animal model demonstrate a defect in the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to the semistarvation associated with renal insufficiency and cannot be corrected by the administration of physiologic amounts of vitamin D(3): it is reversed by massive doses of the vitamin. Neither the metabolism of vitamin D(3) nor the levels of calcium binding protein activity in the duodenal mucosa are affected by renal insufficiency under the conditions employed in the present studies. The results of the present studies strongly suggest that in addition to the recently proposed mechanism involving an interference with the metabolism of vitamin D renal insufficiency also affects the cellular mechanisms for calcium transport in a manner which, while opposite in direction to that of vitamin D, is independent of a direct interaction with the vitamin or its metabolites.
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PMID:Effect of renal insufficiency on the active transport of calcium by the small intestine. 542 27

Only in the duodenum and in the colon calcium is absorbed by a cellular 1,25 alpha-Vitamin D3-dependent transport mechanism. Calcium absorption is highest in the proximal large intestine, about ten times higher than in the duodenum or in the descending colon. 1,25 alpha-Vitamin D3 stimulates calcium transport by genomic (slow effect: synthesis of cytosolic calcium binding protein CabP and basolateral Ca-ATPase) and non-genomic action (rapid effect: transcaltachyia, liponomic effect at the brush border membrane). CabP-dependent translocation across the cytosol is thought to be rate limiting step of cellular calcium transport. However, only about 50% of calcium absorption is cellular mediated but the same amount of calcium convectively is absorbed by transepithelial water flow across the paracellular pathway (solvent drag effect). 1,25 alpha-Vitamin D3 not only activates cellular calcium absorption but also increases paracellular permeability for calcium by an unknown mechanism. However, essential steps in the cascade from the interaction of 1,25 alpha-Vitamin D3 with the specific receptor over the regulation of the synthesis of calcium binding and transporting proteins to the induction of cellular calcium transport are not as yet clearly understood. The exact feedback mechanism of synchronized calcium transport across the distinct subcellular compartments seems also to be resolved. Cellular calcium transport is not found in the jejunum or in the ileum, what can be explained by the absence of specific 1,25 alpha-Vitamin D3-dependent carrier systems in these segments. On the other hand calcium is secreted across the jejunum and ileum by an anomalous solvent drag effect. Hence, intestinal calcium metabolism seems to underlie an eneteroenteral circuit: 1,25 alpha-Vitamin D3-controlled cellular calcium absorption across the duodenum is followed by paracellular calcium secretion across the jejunum and ileum. The carrier in the proximal colon which works at the optimal level already under normal nutritional condition could be of physiological importance for the reclamation of unabsorbed dietary calcium and for the reabsorption of calcium that is secreted across the distal small intestine. Under certain pathophysiological conditions, i.e. malabsorption in proximal segments or malnutrition, calcium in addition may be conserved by the 1,25 alpha-Vitamin D3-sensitive carrier in the descending colon.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[New findings on the mechanism and regulation of intestinal calcium transport]. 780 57

Vitamin D3 is synthesized in the skin during summer under the influence of ultraviolet light of the sun, or it is obtained from food, especially fatty fish. After hydroxylation in the liver into 25-hydroxyvitamin D (25(OH)D) and kidney into 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite can enter the cell, bind to the vitamin D-receptor and subsequently to a responsive gene such as that of calcium binding protein. After transcription and translation the protein is formed, e.g. osteocalcin or calcium binding protein. The calcium binding protein mediates calcium absorption from the gut. The production of 1,25(OH)2D is stimulated by parathyroid hormone (PTH) and decreased by calcium. Risk factors for vitamin D deficiency are premature birth, skin pigmentation, low sunshine exposure, obesity, malabsorption and advanced age. Risk groups are immigrants and the elderly. Vitamin D status is dependent upon sunshine exposure but within Europe, serum 25(OH)D levels are higher in Northern than in Southern European countries. Severe vitamin D deficiency causes rickets or osteomalacia, where the new bone, the osteoid, is not mineralized. Less severe vitamin D deficiency causes an increase of serum PTH leading to bone resorption, osteoporosis and fractures. A negative relationship exists between serum 25(OH)D and serum PTH. The threshold of serum 25(OH)D, where serum PTH starts to rise is about 75nmol/l according to most surveys. Vitamin D supplementation to vitamin D-deficient elderly suppresses serum PTH, increases bone mineral density and may decrease fracture incidence especially in nursing home residents. The effects of 1,25(OH)2D and the vitamin D receptor have been investigated in patients with genetic defects of vitamin D metabolism and in knock-out mouse models. These experiments have demonstrated that for active calcium absorption, longitudinal bone growth and the activity of osteoblasts and osteoclasts both 1,25(OH)2D and the vitamin D receptor are essential. On the other side, bone mineralization can occur by high ambient calcium concentration, so by high doses of oral calcium or calcium infusion. The active metabolite 1,25(OH)2D has its effects through the vitamin D receptor leading to gene expression, e.g. the calcium binding protein or osteocalcin or through a plasma membrane receptor and second messengers such as cyclic AMP. The latter responses are very rapid and include the effects on the pancreas, vascular smooth muscle and monocytes. Muscle cells contain vitamin D receptor and several studies have demonstrated that serum 25(OH)D is related to physical performance. The active metabolite 1,25(OH)2D has an antiproliferative effect and downregulates inflammatory markers. Extrarenal synthesis of 1,25(OH)2D occurs under the influence of cytokines and is important for the paracrine regulation of cell differentiation and function. This may explain that vitamin D deficiency can play a role in the pathogenesis of auto-immune diseases such as multiple sclerosis and diabetes type 1, and cancer. In conclusion, the active metabolite 1,25(OH)2D has pleiotropic effects through the vitamin D receptor and vitamin D responsive elements of many genes and on the other side rapid non-genomic effects through a membrane receptor and second messengers. Active calcium absorption from the gut depends on adequate formation of 1,25(OH)2D and an intact vitamin D receptor. Bone mineralization mainly depends on ambient calcium concentration. Vitamin D metabolites may play a role in the prevention of auto-immune disease and cancer.
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PMID:Vitamin D physiology. 1656 71