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)

Impaired bone metabolism following urinary diversion through intestinal segments has always been a controversial subject of unclear clinical relevance. Whereas the perpetuated pathophysiological considerations seem conclusive in theory, the role of acidosis and malabsorption is less clear in animal experimentation and, even more so, in the clinical reality of modern continent diversion. In hardly any of the available contemporary case series was overt derangement of the acid-base balance, rickets or osteomalacia encountered. No consistent changes in osteotropic serum parameters could be found with normal calcium and phosphate in all patients. The assumption that colonic reservoirs have a higher risk of developing metabolic bone disease could not be confirmed by clinical data. As early correction of base excess is easy and probably a common policy in patients with intestinal urinary reservoirs, it will be virtually impossible to further study the natural history of bone metabolism after urinary diversion. While there is no need for a bone specific follow-up in asymptomatic adults with a normal acid-base balance, particular attention should be paid to children and to all patients with impaired renal function.
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PMID:Bladder, bowel and bones--skeletal changes after intestinal urinary diversion. 1531 38

In order to examine the etiology of refractory rickets, we evaluated the case records of patients presenting between 1990 and 2002. Subjects with impaired renal functions were excluded. Of 131 patients, 25.9 % each had hypophosphatemic rickets and distal renal tubular acidosis (RTA), 19.6 %vitamin D dependent rickets (VDDR), 11.3 % proximal RTA, 9.1 % liver disease and 6.1 % malabsorption. A significant proportion of patients with VDDR and proximal RTA showed deformities in the first year of life, whereas those with distal RTA and hypophosphatemic rickets presented later. Patients with hypophosphatemic rickets had predominant involvement of lower limbs; hypercalciuria was found in 4. Distal RTA was associated with marked rickets and normal levels of alkaline phosphatase. Hypophosphatemia and low tubular reabsorption of phosphate, though characteristic of hypophosphatemic rickets, was also seen in patients with VDDR (19.2%) and distal RTA (17.6 %). Our findings suggest that application and interpretation of appropriate investigations are useful in determining the cause of non-azotemic refractory rickets allowing initiation of specific therapy.
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PMID:Non-azotemic refractory rickets in Indian children. 1569 54

A nearly 5 year-old boy presented with proximal muscle weakness, reduced muscle bulk, a positive Gower sign and Trendelenburg gait. He was known to have cholestatic liver disease. Investigations revealed markedly low serum total calcium, elevated alkaline phosphatase, very low serum 25-hydroxyvitamin D, and radiographs consistent with active rickets despite the ongoing administration of a water-soluble preparation of vitamin D. Only i.v. calcitriol acutely corrected the hypocalcemia, despite trying several oral preparations, suggesting that malabsorption secondary to chronic liver disease was the cause of his rickets. Intramuscular calciferol quickly corrected his muscle weakness and X-ray findings. Myopathy secondary to vitamin D deficiency is an uncommon diagnosis in children. Intermittent calciferol is an inexpensive and practical treatment for vitamin D deficiency, especially if associated with malabsorption.
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PMID:Treatment of malabsorption vitamin D deficiency myopathy with intramuscular vitamin D. 1612 49

Vitamin D signaling is dependent on the availability and turnover of the active Vitamin D receptor (VDR) ligand 1,25-dihydroxycholecalciferol and on the efficiency of VDR transactivation. Activating and inactivating secosteroid metabolizing p450 enzymes, e.g. 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase, are responsible for ligand availability on the basis of substrate production in the skin and of nutritional intake of precursors. Net availability of active hormone depends on the delivery of substrate and the balance of activating and inactivating enzymes. 1Alpha-hydroxylase is the critical activating enzyme. It is expressed in the kidney for systemic supply and in target tissues for local secosteroid activation. It is upregulated in the kidney by low calcium intake and parathyroid hormone, downregulated by phosphatonins and proinflammatory signal transduction. Transactivation of VDR depends on the correct molecule structure, effective nuclear translocation and the presence of the unliganded heterodimer partner retinoid X-receptor (RXR) and other nuclear cofactors. Rapid Vitamin D-dependent membrane associated effects and consecutive second messenger activation exert an own pattern of gene regulation. A membrane receptor for these effects is hypothesized but not yet identified. Rickets is the long known clinical syndrome of impaired Vitamin D signaling due to Vitamin D3 deficiency. It can be caused by inherited defects of the cascade, nutritional deficits, lack of sunlight exposure, malabsorption and underlying diseases like chronic inflammation. It has been shown during the last decades that many modifiers of Vitamin D signaling are targets of disease in terms of inherited and acquired syndromes and that Vitamin D signaling is modulated at multiple levels and is more complex than mere mechanistic ligand/receptor/DNA interaction.
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PMID:Vitamin D signaling is modulated on multiple levels in health and disease. 1640 53

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

Rickets develops when growing bones fail to mineralize. In most cases, the diagnosis is established with a thorough history and physical examination and confirmed by laboratory evaluation. Nutritional rickets can be caused by inadequate intake of nutrients (vitamin D in particular); however, it is not uncommon in dark-skinned children who have limited sun exposure and in infants who are breastfed exclusively. Vitamin D-dependent rickets, type I results from abnormalities in the gene coding for 25(OH)D3-1-alpha-hydroxylase, and type II results from defective vitamin D receptors. The vitamin D-resistant types are familial hypophosphatemic rickets and hereditary hypophosphatemic rickets with hypercalciuria. Other causes of rickets include renal disease, medications, and malabsorption syndromes. Nutritional rickets is treated by replacing the deficient nutrient. Mothers who breastfeed exclusively need to be informed of the recommendation to give their infants vitamin D supplements beginning in the first two months of life to prevent nutritional rickets. Vitamin D-dependent rickets, type I is treated with vitamin D; management of type II is more challenging. Familial hypophosphatemic rickets is treated with phosphorus and vitamin D, whereas hereditary hypophosphatemic rickets with hypercalciuria is treated with phosphorus alone. Families with inherited rickets may seek genetic counseling. The aim of early diagnosis and treatment is to resolve biochemical derangements and prevent complications such as severe deformities that may require surgical intervention.
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PMID:Rickets: not a disease of the past. 1732 6

Serum immunoglobulin behaviour in some infantile diseases of immunological interest has been studied. No differences in Ig class values were observed in cases of rickets. Intestinal malabsorption was accompanied by increased IgA values, whereas other writers have reported steady or even decreased values in this disease. IgG and IgM increases are observed in virus hepatitis. In line with the majority of the literature reports, decreased IgM values were observed in mongolism.
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PMID:[Serum immunoglobulin values in some diseases of infancy]. 1734 4

Following a previous note dealing with rickets, intestinal malabsorption, virus hepatitis and mongolism, the present paper deals with serum immunoglobulin behaviour in thymomegaly, nephrosis and response to TAB vaccination. Thymomegaly was accompanied by increases in all three Ig classes, followed by normalisation of values shortly after steroid treatment. in nephrotic proteinuria, determination of glomerular selectivity via the evaluation of IgG and transferrin clearance was of assistance with respect to prognosis and therapy. Artificial antigen stimulation of healthy and mongoloid subjects with TAB vaccine was not followed by differences in Ig class behaviour; similar stimulation of full-term and immature neonates, however, showed a rapid and frank increase in immature IgM values with respect to the non-stimulated immature subject of equal age and weight.
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PMID:[Serum immunoglobulin patterns in some diseases of infancy]. 1734 5

Along with other organs like prostate, bones and kidney, skin is capable of vitamin D synthesis. Primarily keratinocytes but also macrophages and fibroblasts synthesize active vitamin D from cholesterol precursors by photochemical activation. The synthesized vitamin D functions by binding to nuclear vitamin D receptors. Vitamin D deficiency usually manifests as rickets in childhood although it is today only relevant in diseases characterized by malabsorption due to today's recommended vitamin D prophylaxis. Excessive doses of vitamin D are the usual cause of increased levels. The most common therapeutic target of Vitamin D is psoriasis. Here, topical preparations are usually employed; their anti-proliferative and cell differentiation-promoting action is mediated via binding to cutaneous vitamin D receptors.
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PMID:[Vitamin D and the skin]. 1868 85

Rickets and fractures have been reported in captive polar bears. Taurine (TAU) is key for the conjugation of ursodeoxycholic acid (UDCA), a bile acid unique to bears. Since TAU-conjugated UDCA optimizes fat and fat-soluble vitamin absorption, we asked if TAU deficiency could cause vitamin D malabsorption and lead to metabolic bone disease in captive polar bears. We measured TAU levels in plasma (P) and whole blood (WB) from captive and free-ranging cubs and adults, and vitamin D3 and TAU concentrations in milk samples from lactating sows. Plasma and WB TAU levels were significantly higher in cubs vs captive and free-ranging adult bears. Vitamin D in polar bear milk was 649.2 +/- 569.2 IU/L, similar to that found in formula. The amount of TAU in polar bear milk is 3166.4 +/- 771 nmol/ml, 26-fold higher than in formula. Levels of vitamin D in bear milk and formula as well as in plasma do not indicate classical nutritional vitamin D deficiency. Higher dietary intake of TAU by free-ranging cubs may influence bile acid conjugation and improve vitamin D absorption.
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PMID:Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity? 1923 63


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