Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Diaphyseal bone from normal Sprague-Dawley rats was delipidated in chloroform-methanol and demineralized in 0.6 N HCl at 4 degrees C. The bones were then implanted for 7-28 days into rats made rachitic by a low-phosphate, vitamin D-deficient diet (VDP-) for 3 weeks. Bones from VDP- and normal rats were also implanted into normal hosts. When normal rats were used as the host environment, a consistent sequence of cartilage induction and bone formation was observed. Demineralized rachitic bone (RB) implanted into normal host rats resulted in cartilage and bone induction similar to that seen for normal bone (NB) implants. Transmission electron microscopy of RB in normal hosts revealed morphologically normal chondrocytes and cartilage matrix with normal mineralization. In contrast, implantation of NB in VDP- hosts resulted in delayed chondrogenesis and lack of calcification. Furthermore, similar results were observed when RB was implanted into VDP- hosts. Treatment of VDP- hosts with either 1 alpha-hydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 did not accelerate the sequential appearance of precartilage or cartilage. However, 24,25-(OH)2D3 administered alone or in combination with 1 alpha-OHD3 significantly increased the amount of calcified cartilage observed at 2 weeks postimplantation compared to implants from either untreated VDP-hosts or those treated only with 1 alpha-OHD3. New bone formation was observed at 4 weeks postimplantation in all vitamin D-treated groups as determined by von Kossa staining or direct electron microscope examination. There was no apparent difference in the quantitative or qualitative bone formed within the various vitamin D-treated groups. Serum calcium and phosphorus levels were lower and alkaline phosphatase levels were higher in VDP- hosts compared with normal animals or those treated with vitamin D metabolites. The results of this study show a reduction in the capacity of progenitor cells in VDP- rat hosts to respond to osteoinductive factor(s). This impaired response appears to be corrected by vitamin D metabolites.
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PMID:Enhancement of osteoinduction by vitamin D metabolites in rachitic host rats. 144 1

The disparity in fracture incidence and bone mass in women of European (white) and African (black) ancestry is of unknown etiology. To determine if racial differences in bone mass reflected racial differences in the mechanisms of bone turnover underlying bone mineral loss, we measured serum osteocalcin, serum alkaline phosphatase, fasting urinary calcium and hydroxyproline excretion, 24 h urinary excretion of calcium and sodium, and dietary intakes of calcium and vitamin D in 263 healthy pre-, peri-, and postmenopausal white and black women. In addition, radial and spinal bone density were measured cross-sectionally for comparison with biochemical measures of bone turnover. The biochemical parameters thought to reflect bone resorption (fasting urinary calcium and hydroxyproline excretions) were lower in black than in white women throughout the age and menopausal stages studied. The parameters thought to reflect bone formation (alkaline phosphatase and osteocalcin), were similar in the two racial groups among the premenopausal women, but osteocalcin was significantly lower among the peri- and postmenopausal blacks. Cross sectionally measured radial bone density increased with age in premenopausal black women, but it did not change with age in the white premenopausal subjects, a statistically significant difference. In peri- and postmenopausal women radial density declined significantly with years after menopause in both racial groups, but the rate of decline was significantly slower in the black women. Lumbar bone density in premenopausal white and black women did not change with age. After menopause lumbar bone density declined significantly and similarly in both racial groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Racial differences in pre- and postmenopausal bone homeostasis: association with bone density. 145 86

Thirty-five preterm (< 1500 g) infants were fed preterm human milk (PHM) supplemented with either powdered fortifier (PF) or liquid supplement (LS). Bone mineral content (BMC) of the distal third radius was measured by photon absorptiometry. Biochemical indices of nutritional and bone status were obtained every 2 weeks. The initial BMC for both feeding regimens were similar. BMC did not change over the study period for infants fed LS. Infants fed PF had BMC values greater than LS infants at weeks 2 and 4 of study. Only infants fed PF had BMC values that demonstrated a consistent increase. Serum total protein and phosphorus values were greater for PF infants at week 4 than LS infants. Weight, length, occipital-frontal circumference (OFC) gains, serum albumin, alkaline phosphatase, calcium, and vitamin D levels were similar in both groups. We conclude that products used to "enrich" PHM are adequate to meet the growth needs of the preterm infant. However, we found that infants fed the powdered fortified preterm human milk had higher bone mineralization than those fed the liquid supplemented human milk.
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PMID:Evaluation of liquid or powdered fortification of human milk on growth and bone mineralization status of preterm infants. 146 16

It is said that maintenance hemodialysis patients are already suffering from secondary hyperparathyroidism (2HPT) from early stage of chronic renal failure. The treatment of 2HPT in this stage is very important for preventing renal osteodystrophy (ROD). But many long-term dialysis patients are still afflicted with ROD although vitamin D have been used for treatment. In this study, an oral administration of 1-25 (OH)2 D3 (4 micrograms) with pulse therapy twice a week at the day before hemodialysis was started for 12 weeks. The concentration of 1-25 (OH)2D3, total calcium (Ca), ionized calcium (Ca++), alkaline phosphatase (ALP) and parathyroid hormone (PHT) in serum were measured not only before and after every 2 hours of administration a day, but also for 12 weeks after that. The peak of serum 1-25 (OH)2D3 could be sufficiently elevated after 8 hours, and the slight peak of Ca++ could be seen after 8 hours as well. But the level of total calcium could not increased. Although the level of only HS-PTH has not increased after 24 hours, a significant reduction in serum level of C-PTH, intact-PTH and HS-PTH could be recognized after 12 weeks finally. This pulse therapy was effective in reducing the serum level of PTH in this early stage from beginning hemodialysis. But, it needs further studies for the standard treatment.
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PMID:[The oral 1-25 dihydroxyvitamin D3 pulse therapy in hemodialysis patients for the early treatment of secondary hyperparathyroidism]. 147 20

Postgastrectomy bone disease was a term devised to describe the metabolic disorders of bone which may follow a gastrectomy operation. Although the use of this operation has declined drastically in recent years, this metabolic bone disorder is still with us and may escape and confuse the unwary. These disorders may take the form of osteomalacia, osteoporosis in excess of normal ageing, or a combination of both. For screening purposes, regular estimations of plasma alkaline phosphatase levels identify patients who may be developing osteomalacia which can then be treated with calcium and vitamin D supplements. Numerically, osteoporosis in excess of ageing is a bigger problem and its prevention and treatment is at present unsatisfactory. Screening procedures for osteoporosis are reviewed, including the more recent methods of bone mineral density assessment. Osteopenia or demineralization occurs in both osteomalacia and osteoporosis therefore osteomalacia must be excluded before attributing any loss to osteoporosis. The present situation with regards to the prevention and treatment of osteoporosis is also reviewed.
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PMID:A review of postgastrectomy bone disease. 148 91

Unilateral nephrectomy causes a decrease in provision of vitamin D dihydro derivatives in pregnant rats, which correlated with the development of hypocalcemia and hypophosphatemia as well as with an increased content of parathyroid hormone. Fetuses of these females contained less amount of mineral components and active metabolites of vitamin D. Neonates, being born by these females with the nephrectomy, had vitamin D deficiency, which was manifested as a decrease in content of active vitamin D metabolites and minerals as well as an increase in activity of alkaline phosphatase and in the content of parathyroid hormone.
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PMID:[The effect of unilateral nephrectomy on vitamin D metabolism in pregnant rats]. 149 97

Acromegaly is characterized by growth hormone (GH) hypersecretion and insulin-like growth factor-I (IGF-I) excess, both of which stimulate osteoblast proliferation. At diagnosis, GH excess has usually been present for years. Furthermore, impaired gonadotropin secretion with hypogonadism is frequent. To date, studies of changes in bone mineral density (BMD) in acromegaly have been limited and the available data inconsistent. To investigate the effects of GH excess on proximal femur and lumbar spine BMD, a case series of 25 patients with acromegaly (8 eugonadal, 17 hypogonadal) documented by high plasma GH and IGF-I concentrations was studied. BMD was measured using dual-photon absorptiometry, hormonal and biochemical measurements, which included GH, IGF-I, serum calcium, phosphate, alkaline phosphatase, 1,25 dihydroxy vitamin D and urinary calcium and hydroxyproline excretion. Seven patients were re-studied after IGF-I was suppressed for six months by the somatostatin analog 201-995 (five patients) or pituitary adenomectomy (two patients). BMD was normal in 22 patients and was decreased at one site each in one eugonadal and two hypogonadal patients. BMD was similar between the eugonadal and hypogonadal groups at all sites. Urinary hydroxyproline excretion was equally increased in both groups. There was no correlation between any of the hormonal or biochemical parameters and the age, sex, race and body mass index matched Z-scores of BMD at any site. Following normalization of IGF-I for 6 mo in seven patients, there was no significant change of BMD. We conclude that proximal femoral and lumbar spine BMD is normal in most patients with active acromegaly, including those who are hypogonad. Successful treatment of acromegaly does not result in major short-term changes in BMD.
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PMID:Bone mineral density of the axial skeleton in acromegaly. 151 33

Serum osteocalcin (Gla) and skeletal alkaline phosphatase (SAP) concentration both reflect osteoblast activity in the dynamic process of bone formation. To assess the relation in premature infants between change in bone mineral content (BMC) and both Gla and SAP serum concentration, we longitudinally measured BMC via photon absorptiometry and serum Gla and SAP concentration from birth to 16 wk in 20 very low birth weight infants. Serum total calcium, phosphorus, parathyroid hormone, and vitamin D metabolite concentrations were also monitored. All serum values were measured in the 20 mothers at delivery. Cord blood Gla concentrations were significantly (p less than 0.03) greater than maternal levels, and by 1 wk had significantly (p less than 0.001) increased from birth values. Total calcium, parathyroid hormone, phosphorus, and vitamin D concentrations remained in the normal range throughout the study. The increase in serum Gla concentrations, birth to 1 wk, were significantly correlated with the simultaneous increase in 1,25-dihydroxyvitamin D concentrations. The correlation between the change in BMC, however, over the first 4 mo of life and both Gla and SAP serum concentrations failed to reach statistical significance. Finally, a significant (p less than 0.003) negative correlation was measured between serum Gla and SAP concentrations at wk 4, and, although not significant, a consistently negative correlation was measured from 1-16 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Osteocalcin, skeletal alkaline phosphatase, and bone mineral content in very low birth weight infants: a longitudinal assessment. 154 49

A group of 16 infants, 2 weeks to 11 months old, with malignant osteopetrosis were investigated to examine their vitamin D metabolism and parathyroid function. Bone biopsies from 6 children were studied by light microscopic histomorphometry and by electron microscopy. Considerable heterogeneity existed among the patients with respect to the parameters reflecting mineral metabolism and with respect to the histological manifestations of the disease. The most constant findings were as follows. Immunoreactive parathyroid hormone (iPTH) was elevated in all children, except in 1 patient who had tubular acidosis, and plasma calcium was low or normal, suggesting skeletal resistance to PTH. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] was not constantly elevated and appeared to depend on plasma phosphorus, as both parameters were negatively correlated (r = 0.704, p less than 0.01). Osteoblast activity, as evaluated by circulating alkaline phosphatase and osteocalcin and osteoblast number, measured for 6 children by bone histology, were not increased, despite hyperparathyroidism, suggesting PTH resistance or defective osteoblasts. Osteoclasts could be detected in 5 of the 6 children who had a biopsy. Osteoclast number (5.7-13.3% of bone surface) was normal or mildly increased, and marrow spaces were relatively well developed in 4 patients, whereas 1 child had markedly increased osteoclast number (28.3% of bone surface) and reduced marrow cavities. These 5 children received transplants, and engraftment occurred in all, except in the "hyperosteoclastic" patient. Further studies are necessary to establish the prognostic significance of this histologic feature.
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PMID:Mineral metabolism in infants with malignant osteopetrosis: heterogeneity in plasma 1,25-dihydroxyvitamin D levels and bone histology. 154 52

The synthesis of osteocalcin or bone gla protein by osteoblasts is markedly stimulated by 1,25-(OH)2D, a key hormone in the regulation of bone mineralization. The circulating levels of osteocalcin have been shown to reflect both the osteoid matrix production and the formation rate of mineralized bone in several metabolic bone diseases (osteoporosis, thyrotoxicosis, primary hyperparathyroidism) in which both mechanisms are tightly coupled because of the absence of mineralization defect. In this study, we measured in 12 patients (7 women, 5 men, 56 +/- 15 yr old) with untreated osteomalacia serum osteocalcin and vitamin D metabolites (25OHD and 1,25-(OH)2D). The results were correlated with biochemical and histomorphometric assessment of bone remodeling. Osteomalacia was due to vitamin D deficiency (5 cases), to vitamin D malabsorption (6 cases), and to hypophosphataemia in 1 case. When compared to control values, serum osteocalcin was increased in patients with osteomalacia (7.4 +/- 4 vs. 3.7 +/- 1.3 ng/mL; P less than 0.001) and was positively correlated with serum alkaline phosphatase (r = 0.65; P = 0.03) and negatively with 25 OHD (r = -0.61; P = 0.04). Serum osteocalcin was not correlated with 1,25-(OH)2D [r = -0.45; not significant (NS)] even after exclusion of the patient with hypophosphataemia. Serum osteocalcin was positively correlated with the osteoid volume and osteoid perimeter (r = 0.71 and 0.69 respectively; P less than 0.01) but not with any of the tetracycline-based parameter of bone mineralization at the tissue level (r ranging from -0.41 to +0.42, NS). Serum 25 OHD, but not 1,25-(OH)2D, was positively correlated with the mineralization rate (r = 0.59; P less than 0.05 and r = 0.54; NS). We conclude that in patients with osteomalacia, a condition which is characterized by an increased osteoid accumulation due to a decreased mineralization rate, the increased level of serum osteocalcin reflects the increased osteoid synthesis but not the mineralization defect. In this disease, serum osteocalcin is inversely correlated to the severity of vitamin D deficiency reflected by serum 25 OHD, but not to the serum levels of 1,25-(OH)2D.
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PMID:Serum osteocalcin is increased in patients with osteomalacia: correlations with biochemical and histomorphometric findings. 156 62


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