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)

Previous studies from this laboratory demonstrated that secondary hyperparathyroidism in dogs with chronic renal disease may occur, at least in part, as a consequence of the need for progressive adaptation in renal phosphorus (P) excretion that occurs as glomerular filtration rate falls. However, the studies were of relatively short duration. Moreover, no information emerged regarding a potential role of calcium malabsorption in the pathogenesis of secondary hyperparathyroidism. The short duration of the protocol did not lend itself to the study of the effect of P control or the administration of vitamin D in the pathogenesis of renal osteodystrophy. In the present studies, 14 dogs with experimental chronic renal disease were studied serially for a period of 2 yr. Each animal was studied first with two normal kidneys on an intake of P of 1,200 mg/day. Then, renal insufficiency was produced by 5/6 nephrectomy. The dogs then were divided into three groups. In group I, 1,200 mg/day P intake was administered for the full 2 yr. In group II, P intake was reduced from the initial 1,200 mg/day, in proportion to the measured fall in glomerular filtration rate, in an effort to obviate the renal adaptation in P excretion. In group III, "proportional reduction" of P intake also was employed; but in addition, 20 mug of 25(OH)D(3) were administered orally three times a week. In group I, parathyroid hormone (PTH) levels rose throughout the 2-yr period reaching a final concentration of 557+/-70 U (normal 10-60). In group II, values for PTH remained normal throughout the 1st yr, increased modestly between the 12th and the 18th mo, but then did not rise after the 18th mo. In group III, no elevation of PTH levels was observed at any time; however, these animals were hypercalcemic. Histomorphologic analyses of the ribs of these dogs were performed serially throughout the 2-yr period. A linear relationship was obtained between the osteoclastic resorption surface and the concentration of circulating immunoreactive PTH. The osteoid volume was greater in group I animals when compared to those in group II. None of the morphologic abnormalities associated with renal osteodystrophy were observed in the animals in the third group.
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PMID:Phosphate control and 25-hydroxycholecalciferol administration in preventing experimental renal osteodystrophy in the dog. 87 95

The action of 1 alpha-hydroxycholecalciferol (oxydevit) was estimated in 204 patients with renal osteodystrophy, osteoporosis of varying etiology, osteomalacia because of malabsorption, congenital rickets-like diseases. The drug was shown to be highly effective in the treatment of secondary hyperparathyroidism in uremia, steroidal and senile osteoporosis. The treatment involved replacement therapy.
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PMID:[Experience in treating metabolic osteopathies with 1 alpha-hydroxyvitamin D3 (oksidevit)]. 181 42

There are two sources of vitamin D available to man: The more important source is the cholecalciferol (vitamin D3), which is produced photochemically in the skin from the provitamin, 7-dehydrocholesterol; vitamin D ingested with food is of secondary importance, but assumes a critical role when an individual is deprived of solar exposure. Vitamin D therefore is not strictly a vitamin. A deficiency of vitamin D ultimately results in osteomalacia in adults and rickets in children, and provision of sunlight or small oral doses of the vitamin can cure this bone condition. There are, however, many less common conditions in which small doses of the vitamin are ineffective, whereas larger doses of vitamin D can achieve healing of the bone disease. These conditions are collectively called vitamin D-resistant diseases and include hypoparathyroidism, genetic and acquired hypophosphataemic osteomalacias, renal osteodystrophy, vitamin D-dependent rickets, and the osteomalacia associated with liver disease and intestinal malabsorption. Unfortunately, large doses of vitamin D continue to be prescribed for a wide variety of diseases in which there is little scientific evidence of their efficacy. The benefits and dangers of high doses of vitamin D are discussed and the problems arising from inappropriate or poorly supervised treatment with vitamin D presented. The serum concentration of the active metabolite of vitamin D, 1,25 dihydroxyvitamin D is increased in certain disease states, and the pathophysiology of some these diseases are presented. The exciting developments in tumour differentiation and the role of high doses of 1,25 dihydroxyvitamin D for the control of leukaemia and other blood and skin diseases are discussed.
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PMID:High-dose vitamin D therapy: indications, benefits and hazards. 250 9

The mechanisms of vitamin D deficiency already described are triggered off by a variety of causes. Confinement indoors leads to defective photosynthesis and dietary restrictions to insufficient intake. Malabsorption results from digestive tract diseases: mainly adult coeliac disease, but also sequelae of gastrectomy, exocrine pancreatic insufficiency, chronic biliary obstruction and all other causes of steatorrhoea. Practically, osteomalacia of digestive origin usually results from multifactorial hypovitaminosis D. The same applies to primary or nutritional biliary cirrhosis, which frequently entails low vitamin D blood levels despite subnormal 25-hydroxylation. Osteomalacia is also found in renal osteodystrophy, where it is partly due to inhibition of 1,25-hydroxylase and subsequent deficiency of 1,25-dihydrocholecalciferol, though other, non vitaminic substances may also be involved. Two misleading forms of the disease must be borne in mind: one with renal tubular lsions, the other associated with functional pseudo-hypoparathyroidism. The aetiology of most cases of osteomalacia due to vitamin D deficiency can be elucidated by a few simple tests.
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PMID:[Osteomalacia due to vitamin D deficiency. Part two: Aetiology (author's transl)]. 742 86

1. The best way to prevent early growth failure in children with renal disease is by the use of specified nutrition and appropriate buffer, activated vitamin D, and calcium-containing phosphate binders as needed. With prenatal diagnosis of anatomically abnormal kidneys available, this type of early intervention may be much more feasible in the 1990s. 2. Supplemental sodium and water in children with polyuria and intravascular volume depletion may prevent growth failure. Cow milk is detrimental in this group of individuals because of high solute and protein load, often causing intravascular volume depletion, hyperphosphatemia, and acidosis. 3. Children with acquired glomerular disease may need sodium restriction and, if treated with steroids, a diet low in saturated fat. 4. Children with nephrotic syndrome and severe edema should be evaluated for malabsorption and subsequent malnutrition. Protein intake should be supplemented only at the RDA and to replace ongoing losses. Long-term sodium restriction is appropriate. Hyperlipidemia should be monitored: if nephrosis is chronic, a low saturated fat diet should be instituted. Angiotensin-converting enzyme inhibitors can decrease urinary protein loss and may ameliorate hyperlipidemia. Children resistant to therapy can have very high morbidity. 5. Children with <50 % of normal creatinine clearance should have PTH measured and activated vitamin D therapy should be started if PTH is elevated more than two to three times normal. Thereafter careful monitoring of calcium, phosphorus, and PTH is crucial to prevent renal osteodystrophy, low turnover bone disease, and hypercalcemia with hypercalciuria and nephrocalcinosis. 6. Children with tubular defects with severe polyuria also may benefit from low-solute, high-volume feedings. 7. All physicians caring for children with renal disease should have pediatric nephrology consultation available. Prevention of growth failure is much more cost effective than pharmacologic therapy. Before initiating growth hormone treatment for growth retardation, assiduous treatment of co-existing renal osteodystrophy and provision of optimal nutritional intake should be accomplished.
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PMID:Nutritional management of the child with mild to moderate chronic renal failure. 876 44

In 1981, Chugai Pharmaceutical succeeded in marketing alfacalcidol, a prodrug of calcitriol, as a therapeutic agent for renal osteodystrophy. In 1983, Chugai succeeded in extending the application of alfacalcidol to the treatment of osteoporosis as well. Clinicians in Japan have accepted alfacalcidol as a remedy for osteoporosis. However, the use of calcitriol and its analogs for the treatment of osteoporosis is still controversial. Some misunderstandings exist internationally about the efficacy of the active form of vitamin D for the treatment of osteoporosis. It is important to emphasize that patients with osteoporosis have intestinal calcium malabsorption and dysfunction in renal activation of vitamin D. When massive doses of parent vitamin D were administered to OVX rats, bone mass increased, but surprisingly, many porotic area were observed in the cortical bone. On the other hand, administration of alfacalcidol increased physiological bone without porotic observation. It is necessary to give the active form of vitamin D, D-hormone, with an RDA-equivalent supply of calcium. Alfacalcidol forms physiological strong bones that are hardly fractured by regulating calcium and bone metabolism. We proposed a new vitamin D analog, 2beta (3-hydroxypropoxy)calcitriol [ED-71] as a therapeutic drug for osteoporosis, which is more potent than calcitriol. ED-71 is now being investigated in phase 2 clinical studies in Japan. ED-71 will appear as more improved drugs for osteoporosis until 2010.
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PMID:Rationale for active vitamin D and analogs in the treatment of osteoporosis. 1252 May 40