Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of aluminum exposure on bone formation employing the demineralized bone matrix (DBM) induced bone development model were studied using 4-week-old Sprague-Dawley rats injected with a saline (control) or an aluminum chloride (experimental) solution. After 2 weeks of aluminum treatment, 20-mg portions of rat DBM were implanted subcutaneously on each side in the thoracic region of the control and experimental rats. Animals were killed 7, 12, or 21 days after implantation of the DBM and the developing plaques removed. No morphological, histochemical, or biochemical differences were apparent between plaques from day 7 control and experimental rats. Plaques from day 12 control and experimental rats exhibited cartilage formation and alkaline phosphatase activity localized in osteochondrogenic cells, chondrocytes, osteoblasts, and extracellular matrix. Unlike the plaques from control rats that contained many osteoblastic mineralizing fronts, the plaques from the 12-day experimental group had a preponderance of cartilaginous tissue, no evidence of mineralization, increased levels of alkaline phosphatase activity, and a reduced calcium content. Plaques developing for 21 days in control animals demonstrated extensive new bone formation and bone marrow development, while those in the experimental rats demonstrated unmineralized osteoid-like matrix with poorly developed bone marrow. Alkaline phosphatase activity of the plaques continued to remain high on day 21 for the control and experimental groups. Calcium levels were significantly reduced in the experimental group. These biochemical changes correlated with histochemical reductions in bone calcification.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of short-term aluminum exposure on demineralized bone matrix induced bone formation. 129 Apr 3

Extraskeletal pseudotumoral calcifications generally develop in uremic patients with a high calcium x phosphorus (Ca x P) product and severe secondary hyperparathyroidism. In the present case report we describe a chronic hemodialysis patient presenting with a massive calcification of the left shoulder region, severe aluminum (Al) intoxication and moderate hyperparathyroidism. Her initial serum Ca x P product was only slightly elevated: 5.01 mmol2/l2. Under deferoxamine treatment during the subsequent 4 months, Al overload decreased. On the other hand, parathyroid overfunction worsened, as reflected by an increase of the serum immunoreactive parathyroid hormone [1-84] level from initially 690 to 1052 pg/ml (normal, 15-60 pg/ml) and an increase of alkaline phosphatase activity, and plasma calcitriol increased from undetectable to a low-normal value. Predialysis serum total Ca levels decreased rapidly from 2.9 to 2.5 mM but serum P concentrations remained elevated: 1.6-2.5 mM. Unexpectedly, the extent of the periarticular calcification diminished considerably during the same time period. The present observation shows that in a subset of uremic patients with Al overload, pseudotumoral calcifications may regress during Al chelation therapy despite progression of hyperparathyroidism. Since Al may predispose collagen to develop dystrophic or metastatic calcification, it is suggested that this process is reversible by correcting Al intoxication.
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PMID:Decrease of tumor-like calcification in uremia despite aggravation of secondary hyperparathyroidism: a case report. 139 70

Uremic patients may develop extraskeletal calcifications. Among the latter, periarticular tumoral calcifications (TC) represent massive, multiloculated calcium-phosphate deposits. The aim of this report was to analyze a series of 10 cases of TC in hemodialysis patients who were admitted at the Necker Hospital between 1974 and 1988. They were all male. An increased plasma calcium x phosphorus product was observed in 8 of the 10 patients. Plasma calcium level was increased in only 2 patients. In contrast, hyperphosphatemia was a constant feature in all the patients, as was the absence of an increase in plasma alkaline phosphatase activity. Using the bone histomorphometry technique, osteitis fibrosa of mild degree was observed in 2 patients, of moderate degree in 2 and of severe degree in 2 others. Evidence of aluminum (Al) overload was found in the 8 patients in whom it was searched based on bone histomorphometry, bone histochemistry, bone Al content and increased serum Al levels either in the basal state or after a deferoxamine test. In addition, Al overload was strongly suspected in the 2 remaining patients because of prolonged exposure to Al-contaminated dialysate. Various treatment strategies, including parathyroidectomy (PTx), were undertaken that remained unsuccessful in modifying the course of TC to a significant extent. Remarkably, TC occurred for the first time after PTx in 1 patient and worsened after PTx in 2 others. In conclusion, overt secondary hyperparathyroidism appears not to be an essential prerequisite for TC development in hemodialysis patients, and PTx must not be performed in such patients on the sole basis of the presence of TC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumoral calcifications in hemodialysis patients: possible role of aluminum intoxication. 156 77

Parathyroid hormone (PTH), osteocalcin and alkaline phosphatase (AP) were investigated before and after parathyroidectomy in 12 patients receiving hemodialysis. Early post-parathyroidectomy, PTH decreased (p less than 0.001), AP increased (p less than 0.05), but osteocalcin remained unchanged. At 3 months, osteocalcin and AP declined. A negative correlation was observed between aluminum staining and post-parathyroidectomy osteocalcin. In conclusion, early post-parathyroidectomy, osteocalcin and AP reflect persistent osteoblastic activity, which declined after 3 months. In patients receiving hemodialysis both variables may represent different aspects of osteoblastic activity and osteocalcin allows mixed uremic osteodystrophy after parathyroidectomy.
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PMID:Evolution of osteocalcin, alkaline phosphatase and parathyroid hormone after parathyroidectomy in patients receiving chronic maintenance hemodialysis. 157 55

Due to toxic side effects of aluminum-containing agents for treatment of uremic hypophosphatemia, much interest has been focused upon aluminum-free phosphate binder alternatives. From results of experimental studies with calcium acetate, this salt has been suggested as a possible effective and safe phosphate binder. In the present study, calcium acetate was used during a mean of 11 months for serum phosphate control in 30 uremic patients previously treated with aluminum and/or calcium carbonate. Satisfactory control of serum phosphate was achieved during the study (mean phosphate concentration +/- SE: 2.15 +/- 0.12 mmol/l compared to prestudy 2.23 +/- 0.19 mmol/l). Mean serum concentrations of calcium, alkaline phosphatase and parathyroid hormone did not change significantly during the study. Serum aluminum decreased significantly (p less than 0.01). Moderate hypercalcemia was observed in 6 patients. Calcium acetate treatment was withdrawn in 2 patients due to gastrointestinal discomfort. It is concluded that calcium acetate seems to be an effective phosphate binder alternative with relatively few side effects.
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PMID:Calcium acetate used as phosphate binding treatment in uremic hyperphosphatemia. 168 Apr 30

The epidemiology of amyotrophic lateral sclerosis (ALS) in the Western Pacific indicates that low concentrations of calcium (Ca) and magnesium (Mg) and high levels of aluminum (Al) in soil and water in these foci are etiologically important. To determine the biochemical derangements and metal deposition induced by chronic dietary deficiencies of Ca, we maintained experimental animals on several regimens. Male Wistar rats, weighing 100g, were fed either a standard diet, low Ca diet, low Ca-Mg diet, or low Ca-Mg diet with high Al for 90 days. Ca, Mg and Al content was determined in central nervous system (CNS) tissues and bone using inductively coupled plasma emission spectrometry (ICP). In separate studies, five male Japanese macaques (Macaca fuscata), weighing 3.5 to 5 kg, were fed alternately with diets, normal in Ca, low in Ca, low in Mg, low in Ca-Mg, or low in Ca-Mg with added Al for four-week periods. Serum Ca, Mg, Al, parathyroid hormone (PTH), bone Gla-protein (BGP) and alkaline phosphatase (ALP) were measured after feeding each dietary regimen. Ca and Mg levels in lumbar vertebrae and femur were significantly reduced and bone Al levels were significantly increased in rats fed diets deficient in Ca alone or diets low in Ca-Mg with or without added Al. Al content in bones was also higher in rats fed the Ca deficient diets. In monkeys fed the low Ca-Mg diet with added Al, reduced levels of serum Ca and Mg, serum PTH, BGP, and ALP were apparent. Our data support the conjecture that deranged bone mineralization induced by chronic dietary deficiency of Ca accelerates mobilization of Ca and Mg from bone and deposition in brain.
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PMID:Evaluation of magnesium, calcium and aluminum metabolism in rats and monkeys maintained on calcium-deficient diets. 174 43

The authors reviewed the clinical usefulness of routine comprehensive skeletal surveys in monitoring renal osteodystrophy in 66 patients on chronic maintenance hemodialysis. Only fourteen (22%) of the 66 patients had roentgenographic evidence of hyperparathyroid bone disease. There were no significant differences in serum calcium, phosphate, or aluminum levels between patients with and without evidence of phalangeal subperiosteal bone resorption in the hands. However, serum levels of parathyroid hormone (PTH) (both intact and mid-molecule) and alkaline phosphatase values were significantly higher in the group with subperiosteal bone resorption (p less than 0.01 and p less than 0.02, respectively). Serum intact PTH correlated with alkaline phosphatase better than the mid-molecule assay. Neither intact nor mid-molecule PTH values correlated with serum calcium, phosphate, or aluminum. Hand roentgenograms were most sensitive in detecting early changes of hyperparathyroidism; symphysis pubis was the next best. Other skeletal roentgenographic findings were less revealing, and in a subset of 20 patients, roentgenograms correlated poorly with bone histology. During this study the authors found an 8% prevalence of vertebral compression fractures; all in postmenopausal white women.
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PMID:Skeletal surveys in renal osteodystrophy. 176 1

The present review summarizes the characteristics of renal bone disease in pediatric patients treated with maintenance peritoneal dialysis. Fifty-eight patients underwent iliac crest bone biopsy after double tetracycline labeling, measurements of aluminum in bone and various serum biochemical determinations including serum PTH, alkaline phosphatase, calcium, phosphorus and aluminum. Evidence of osteitis fibrosa was present in 45% of patients and mild lesions of secondary hyperparathyroidism were found in an additional 25%. Thus, secondary hyperparathyroidism remains the predominant bone lesion despite the use of oral calcitriol. Evidence of aluminum accumulation was substantially less prevalent, findings not surprising due to the widespread use of calcium carbonate as the main phosphate binder agent. However, aplastic bone lesion without aluminum staining was present in the majority of patients with low-turnover lesions of the bone without osteomalacic findings. The long-term evolution of such lesions remains to be evaluated. The potential value of alternative modes of calcitriol administration for the control of secondary hyperparathyroidism is discussed as well as the differences in the bioavailability of sterol according to the different routes for calcitriol administration.
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PMID:Renal bone disease in pediatric patients receiving treatment with maintenance peritoneal dialysis. 177 95

Micromolar concentrations of aluminum sulfate consistently stimulated [3H]thymidine incorporation into DNA and increased cellular alkaline phosphatase activity (an osteoblastic differentiation marker) in osteoblast-line cells of chicken and human. The stimulations were highly reproducible, and were biphasic and dose-dependent with the maximal stimulatory dose varied from experiment to experiment. The mitogenic doses of aluminum ion also stimulated collagen synthesis in cultured human osteosarcoma TE-85 cells, suggesting that aluminum ion might stimulate bone formation in vitro. The effects of mitogenic doses of aluminum ion on basal osteocalcin secretion by normal human osteoblasts could not be determined since there was little, if any, basal secretion of osteocalcin by these cells. 1,25 Dihydroxyvitamin D3 significantly stimulated the secretion of osteocalcin and the specific activity of cellular alkaline phosphatase in the human osteoblasts. Although mitogenic concentrations of aluminum ion potentiated the 1,25 dihydroxyvitamin D3-dependent stimulation of osteocalcin secretion, they significantly inhibited the hormone-mediated activation of cellular alkaline phosphatase activity. Mitogenic concentrations of aluminum ion did not stimulate cAMP production in human osteosarcoma TE 85 cells, indicating that the mechanism of aluminum ion does not involve cAMP. The mitogenic activity of aluminum ion is different from that of fluoride because (a) unlike fluoride, its mitogenic activity was unaffected by culture medium changes; (b) unlike fluoride, its mitogenic activity was nonspecific for bone cells; and (c) aluminum ion interacted with fluoride on the stimulation of the proliferation of osteoblastic-line cells, and did not share the same rate-limiting step(s) as that of fluoride. PTH interacted with and potentiated the bone cell mitogenic activity of aluminum ion, and thereby is consistent with the possibility that the in vivo osteogenic actions of aluminum ion might depend on PTH. In summary, low concentrations of aluminum ion could act directly on osteoblasts to stimulate their proliferation and differentiation by a mechanism that is different from fluoride.
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PMID:Aluminum stimulates the proliferation and differentiation of osteoblasts in vitro by a mechanism that is different from fluoride. 192 12

The case of a 75-year-old woman with severe osteomalacia secondary to ingestion of large amounts of an aluminum-containing antacid is reported. Biochemical analysis revealed signs of phosphate malabsorption and increased levels of bone markers (S-alkaline phosphatase and U-hydroxyproline). A 99mTc-bone scan revealed multiple areas of increased uptake. The patient was normocalcaemic, with normal serum levels of intact parathyroid hormone and 25-hydroxyvitamin D. Serum 1,25-dihydroxyvitamin D was high normal. A transiliac bone biopsy from the patient showed severe osteomalacia. Symptoms, biochemical parameters, bone scan and bone morphology were all normalized 1 year after stoppage of antacid ingestion and treatment with vitamin D2. calcium phosphate and sodium fluoride because of severe osteopeni. The characteristics of this condition and the role of phosphate depletion and aluminum in the pathogenesis of bone lesions are discussed.
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PMID:Antacid-induced osteomalacia: a case report with a histomorphometric analysis. 200 45


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