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

---

Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of vitamin D deficiency was evaluated in a population of elderly institutionalized subjects in seven long-term geriatric care facilities in France (Amiens, Francheville, Ivry, Lille, Montpellier, Oissel and Villejuif). Residents whose functional capability was relatively good were entered into the study. There were 126 patients (99 females and 27 males) with a mean age +/- SD of 84 +/- 6.6 years. All subjects had been institutionalized for over six months and were capable of walking at least as far as the dining room. None had received vitamin D or other compounds known to affect the metabolism of phosphorus and calcium within six months before the study. Vitamin D status was evaluated by determining serum 25 hydroxyvitamin D (25 OH D) levels using a radiocompetition assay after extraction and chromatographic separation. Mean serum 25 OH D was 3.17 +/- 2.52 ng/ml (median 2.5). Eighty-five per cent of subjects had serum 25 OH D values of less than 5 ng/ml and 98% had values under 10 ng/ml, which is the cutoff usually taken to define vitamin D deficiency. Mean serum levels of intact parathyroid hormone were increased approximately two-fold as compared with values in healthy adults (70 +/- 39 pg/ml versus 33 +/- 12 pg/ml). Biochemical markers for bone formation (alkaline phosphatase, osteocalcin) and bone resorption (TRAP, hydroxyproline, pyridinoline) were all increased, with mean values 1.4-fold to 3.4-fold those seen in healthy adults. Serum 25 OH D levels were negatively correlated with serum intact parathyroid hormone levels (r = 0.41; p < 0.0001). Serum intact parathyroid hormone levels were positively correlated with alkaline phosphatase activity (r = 0.30; p < 0.001) and serum osteocalcin levels (r = 0.36; p < 0.0001) and negatively correlated with corrected serum calcium levels (r = -0.20; p < 0.02). Conclusion. Our data demonstrate that severe vitamin D deficiency is present in virtually all elderly institutionalized subjects and is accompanied with secondary hyperparathyroidism responsible for increases in markers of bone remodeling. Routine vitamin D supplementation is warranted in elderly institutionalized subjects.
...
PMID:Prevalence and biological consequences of vitamin D deficiency in elderly institutionalized subjects. 857 30

To examine the relation of the vitamin D status and the remaining estrogen activity with bone turnover and bone mineral density (BMD) in elderly women, BMD was measured at both hips using dual-energy X-ray absorptiometry and at the distal radius using single photon absorptiometry, in 330 healthy women aged 70 and over. Vitamin D metabolites, sex hormone binding globulin (SHBG), PTH(1-84), osteocalcin, alkaline phosphatase, and hydroxyproline and calcium excretion in 2 h fasting urine were measured. Multiple linear regression was used to adjust for potential confounders. In 65% of the women, serum 25(OH)D was below 30 nmol/l. Only values below a threshold for 25(OH)D were negatively related to serum PTH(1-84) (p = 0.02, threshold at 25 nmol/l) and to osteocalcin levels (p = 0.04, threshold at 30 nmol/l). BMD of the femoral neck and trochanter was positively related to serum 25(OH)D (left neck p = 0.001) with thresholds at 30 nmol/l whereas the distal radius was not (p = 0.32). Serum PTH was negatively related to BMD at all measurement sites (all p < 0.001). Serum SHBG, an inverse measure of estrogen activity, was positively related to osteocalcin levels (p = 0.004) and the urinary hydroxyproline/creatinine ratio (p = 0.002) and negatively related to the BMD of the trochanter (left trochanter p = 0.02) and the distal radius (p = 0.001). We conclude that in elderly women, serum 25(OH)D levels below 30 nmol/l are associated with secondary hyperparathyroidism and increased bone turnover. SHBG is positively related to bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women. 858 20

Matrix vesicles are extracellular organelles produced by cells that mineralize their matrix. They contain enzymes that are associated with calcification and are regulated by vitamin D metabolites in a cell maturation-dependent manner. Matrix vesicles also contain metalloproteinases that degrade proteoglycans, macromolecules known to inhibit calcification in vitro, as well as plasminogen activator, a proteinase postulated to play a role in activation of latent TGF-beta. In the present study, we examined whether matrix vesicle metalloproteinase and plasminogen activator are regulated by 1, 25(OH)2D3 and 24,25(OH)2D3. Matrix vesicles and plasma membranes were isolated from fourth passage cultures of resting zone chondrocytes that had been incubated with 10(-10)-10(-7) M24, 25(OH)2D3 or growth zone chondrocytes incubated with 10(-11)-10(-8) M 1,25(OH)2D3, and their alkaline phosphatase, active and total neutral metalloproteinase, and plasminogen activator activities determined. 24,25(OH)2D3 increased alkaline phosphatase by 35-60%, decreased active and total metalloproteinase by 75%, and increased plasminogen activator by fivefold in matrix vesicles from resting zone chondrocyte cultures. No effect of vitamin D treatment was observed in plasma membranes isolated from these cultures. In contrast, 1,25(OH)2D3 increased alkaline phosphatase by 35-60%, but increased active and total metalloproteinase three- to fivefold and decreased plasminogen activator by as much as 75% in matrix vesicles isolated from growth zone chondrocyte cultures. Vitamin D treatment had no effect on plasma membrane alkaline phosphatase or metalloproteinase, but decreased plasminogen activator activity. The results demonstrate that neutral metalloproteinase and plasminogen activator activity in matrix vesicles are regulated by vitamin D metabolites in a cell maturation-specific manner. In addition, they support the hypothesis that 1,25(OH)2D3 regulation of matrix vesicle function facilitates calcification by increasing alkaline phosphatase and phospholipase A2 specific activities as well as metalloproteinases which degrade proteoglycans.
...
PMID:Vitamin D metabolites regulate matrix vesicle metalloproteinase content in a cell maturation-dependent manner. 868 79

Vitamin D deficiency reduces insulin secretion and still occurs in East London Asians in whom the prevalence of diabetes mellitus is at least four times that of Caucasians. Vitamin D status was assessed in 44 of 65 non-diabetic subjects 'at risk' of diabetes (spot blood glucose level >6.0 mmol/l <2 h post cibum, or>4.6 mmol/l >2 h post cibum on two separate occasions) and in 15 of 60 age and sex-matched 'low-risk' control subjects who attended for oral glucose tolerance test (OGTT) after screening of 877 omnivorous subjects not known to have diabetes. It was found that 95% of at-risk and 80% of low-risk subjects were vitamin D deficient (serum 25-hydroxy-vitamin D <11 ng/ml). Diabetes was present in 16, impaired glucose tolerance in 12 and normoglycaemia in 19 at-risk subjects, imparied glucose tolerance in 2, and normoglycaemia in 13 low-risk subjects. Correlation of 30-min OGTT blood glucose, specific insulin and C-peptide levels with 25-hydroxy-vitamin D concentrations in 44 at-risk subjects were -0.31 (p=0.04), 0.59 (p=0.0001) and 0.44 (p=0.006). In 15 'not-at-risk' subjects 30-min OGTT specific insulin and C-peptide levels correlated with 25-hydroxy-vitamin D, r=0.39 (p=0.04) and 0.16 (p=0.43), respectively. Serum alkaline phosphatase concentration was higher in at-risk than not-at-risk subjects (59.6 vs 46.5 IU/l, p=0.012); corrected calcium concentrations were comparable (2.38 vs 2.39 mmol/l, p=0.7). Following treatment with 100,000 IU vitamin D by i.m. injection, specific insulin, C-peptide [30 min on OGTT] and 25-hydroxy-vitamin D concentrations had risen 8-12 weeks later [mean +/- DS] from 57 +/- 62 to 96.2 +/- 82.4 mU/l [p=0.0017], 1.0 +/- 0.4 to 1.7 +/- 0.8 pmol/ml [p=0.001] and 3.6 +/- 1.8 to 13.5 +/- 7.4 ng/ml [p=0.0001], (but not to low-risk group values of 179 +/- mU/l, 2.7 +/- 1.14 pmol/ml and 8.16 +/- 6.4 ng/ml), respectively. Both total serum alkaline phosphatase and corrected calcium concentrations rose following vitamin D treatment in the at-risk subjects by 11.1 +/- 8.22 (from 44 to 55 IU/l) and 0.15 +/- 0.18, (2.43 to 2.57 mmol/l), respectively (p=0.004). Abnormal glucose tolerance was unchanged by vitamin D treatment. The value of early and sustained repletion with vitamin D in diabetes prophylaxis should be examined in communities where vitamin D depletion is common.
...
PMID:Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. 869 Jan 78

Fat soluble vitamins (except vitamin K) are protein bounded with subsequent storage in the body. It is generally accepted that plasma level of vitamin A is increased in majority of patients with chronic renal insufficiency (CRI) including those on continuous ambulatory peritoneal dialysis (CAPD). Thus, there is no need to supplement this vitamin in CRI patients (pts). Plasma level of vitamin E in CRI pts may be elevated, normal or decreased. It seems to be justified to supplement this vitamin, in spite of its normal plasma level, in case platelet aggregation is increased. Both in dialyzed and nondialyzed CRI pts a normal serum level of vitamin K has been observed. Decreased or extremely low serum level of vitamin D following the gradual loss of renal tissue is to be observed in CRI pts. This deficit is regarded as the main factor leading to the decrease in serum level of calcium, the secondary hyperparathyroidism and bone changes. Treatment with 1.25(OH)2D3 (calcitriol) proved to be most successful in alleviation of symptoms resulting from the deficit of vitamin D3 in the body. Intravenous "pulsating" administration of calcitriol results in rapid normalization of serum PTH level. Treatment with 25(OH)D3 (calcidiol) given orally 3 times a week ("pulsating" method) revealed also fairly good results in this respect. During treatment with vitamin D3 hypercalcemia tends to develop, serum alkaline phosphatase normalizes, elevated PTH serum level decreases. Vitamin D metabolites are less active than 1.25(OH)2D3 being less hypercalcemic.
...
PMID:[Vitamin disturbances in chronic renal insufficiency. II. Fat soluble vitamins]. 871 Nov 72

X-linked hypophosphatemia is a metabolic bone disease occurring in both humans and mice. In mice, two different mutations (Hyp and Gy), occurring at separate but closely linked loci, have been proposed as models for this disease. Varying reports of the Vitamin D status of these two mutants has led us to reexamine the influence of diet on circulating calcitrophic hormones and mineral metabolism in both mutants. Hyp and Gy mice were raised on the B6C3H background, and both normal females and heterozygous mutant females were studied at 10 weeks of age. Animals were fed one of three diets at random: high (1.5% Ca and 1.0% P); medium (0.6% Ca and 0.6% P); or low (0.0% Ca and 0.6% P). After 3 days, serum and urine samples were collected. In comparison to mutant mice fed the high diet, both Hyp and Gy mice fed the low diet had decreased serum calcium levels, and further elevations in both serum alkaline phosphatase and serum parathyroid hormone (PTH). Serum 1,25-dihydroxyvitamin D levels were elevated by both the medium and low diets in all groups of mice over values obtained with the high diet. Mutant mice were significantly higher in serum PTH on all diets compared to normal mice fed the same diet. Mutant mice were not elevated in serum 1,25-dihydroxyvitamin D over normal mice when fed the high diet. However, both Hyp and Gy mice fed the medium and low diets were elevated in serum 1,25-dihydroxyvitamin D over normal mice. Serum PTH levels were correlated to serum 1,25-dihydroxyvitamin D levels with Hyp and Gy mice lying on the same line (r = 0.86; p < 0.0001). In summary, when Hyp and Gy mice are studied on the same genetic background and fed the same diet, similar responses are seen in PTH levels and 1,25-dihydroxyvitamin D levels. Both mutants should be useful in elucidating the pathophysiology of this poorly understood human disease.
...
PMID:Effects of altered diet on serum levels of 1,25-dihydroxyvitamin D and parathyroid hormone in X-linked hypophosphatemic (Hyp and Gy) mice. 871 33

The effects of GH substitution on skeletal mass, bone turnover, and calcium metabolism were investigated in 29 patients with GH deficiency who were randomized to sc injections with GH (2 IU/m2 day) or placebo for 12 months. During GH treatment, serum insulin-like growth factor I increased 263 +/- 98% (P < 0.001). Serum osteocalcin, bone a alkaline phosphatase, and procollagen type I C-terminal propeptide increased by 376 +/- 78% (P < 0.005), 128 +/- 17% (P < 0.005), and 100 +/- 17% (P < 0.005), respectively. Serum type I collagen telopeptide and urinary levels of pyridinoline, deoxypyridinoline, and hydroxyproline rose by 158 +/- 39% (P < 0.005), 170 +/- 48% (P < 0.005), 156 +/- 78% (P < 0.005), and 161 +/- 50% (P < 0.005), respectively. Serum ionized calcium rose by 1.7 +/- 0.6% (P < 0.05), whereas serum PTH decreased insignificantly. Vitamin D metabolites remained unaltered. Urinary calcium/creatinine increased and phosphate/creatinine decreased transiently, returning to baseline values at 9 months. When measured by dual energy x-ray absorptiometry, whole body bone mineral density (BMD) and (BMD) of the radius decreased 2.4 +/- 0.6% (P < 0.05) and 3.5 +/- 1.0% (P < 0.005), respectively, whereas no significant changes were observed in BMD of the femur or spine. Our results indicate that long term GH treatment activates bone remodeling in patients with GH deficiency. The observed slight decrease in BMD may be explained by expansion of the remodeling space and reduced mean age of bone tissue. IT remains unclear whether long term treatment with GH will lead to an increase in bone mass and improved skeletal biomechanical competence.
...
PMID:Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study. 878 96

The efficacy of subtotal parathyroidectomy (n = 11), total parathyroidectomy+autotransplantation (n = 13) and total parathyroidectomy alone (n = 24) were compared in a series of renal patients with hyperparathyroidism. The principal indication for surgery was severe bone disease but other indications were uncontrolled hypercalcaemia, soft tissue calcification and grossly elevated parathyroid hormone (PTH) levels. The clinical success rates at 24 months follow-up for subtotal, total plus autograft, and total parathyroidectomy were 100, 89 and 97% respectively. Similar improvements in radiological changes and alkaline phosphatase levels were seen in all three groups. Recurrent hyperparathyroidism was recorded in three (27%) members of the subtotal parathyroidectomy group and two (16%) of the patients undergoing total parathyroidectomy and autotransplantation. Two patients required re-exploration of their forearm parathyroid autograft. No patients undergoing total parathyroidectomy only suffered persistent or recurrent hypercalcaemia. Vitamin D analogue requirements rates in patients undergoing subtotal, total plus autotransplant, and total parathyroidectomy at 24 months were 44, 70 and 81% respectively. An important finding is the demonstration of residual parathyroid function in 14/16 patients (87.5%) undergoing total parathyroidectomy without autotransplantation and followed-up for 2 years.
...
PMID:Parathyroidectomy in chronic renal failure: comparison of three operative strategies. 962 48

: There is a decline in serum 25 hydroxyvitamin D (25OHD), 1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption with advancing age, which may lead to secondary hyperparathyroidism and bone loss. Studies show a relationship between serum 25OHD and bone density in older men and women, with an inverse correlation between bone density and parathyroid hormone (PTH). Vitamin D supplementation in this age group improves calcium absorption, suppresses PTH, and decreases bone loss. Vitamin D many also reduce the incidence of hip and other nonvertebral fractures, particularly in the frail elderly who are likely to have vitamin D deficiency. Patients with established vertebral osteoporosis have lower calcium absorption than age-matched control subjects, possibly due to reduced serum 1,25(OH)2D or to relative resistance to the action of vitamin D on the bowel. Malabsorption of calcium in women with vertebral crush fractures does not usually respond to treatment with physiological doses of vitamin D, but can be corrected by pharmacological doses of vitamin D or by low doses of calcitriol or alfacalcidol. In a recent randomized, controlled study in 46 elderly women with radiological evidence of vertebral osteoporosis, alfacalcidol 0.25 micro;g twice daily improved calcium absorption, decreased serum PTH, and reduced alkaline phosphatase, whereas vitamin D2 500-1000 IU daily had no effect over the 6-month study period. Studies of the effect of the vitamin D metabolites in the management of elderly women with established vertebral osteoporosis have yielded conflicting results, but suggest that alfacalcidol and calcitriol may decrease spinal bone loss and reduce the incidence of vertebral fractures. Although vitamin D supplementation decreases bone loss and fracture risk in the frail elderly, vitamin D metabolites may prove more useful in the treatment of elderly women with vertebral osteoporosis.
...
PMID:Is there a differential response to alfacalcidol and vitamin D in the treatment of osteoporosis? 903 Apr 91

Vitamin D metabolites can prevent estrogen depletion-induced bone loss in ovariectomized (OVX) rats. In this study, we investigated the bone-sparing effects of oral 1alpha,24R,25-trihydroxyvitamin D3 (1,24,25(OH)3D3) in a wide dose range in aged OVX rats. Fifty-three female Fischer-344 rats (6 months old, 170 g BW) were either ovariectomized or sham-operated (SHAM). Eight rats served as baseline controls. Groups of OVX rats (n = 7-8 each) received vehicle alone or graded oral doses of 1,24,25(OH)3D3 (0.05, 0.1, 0.2, and 0.3 microg/kg BW/day), starting five days after surgery. Urine and blood samples were collected one, two, three, and four months after surgery. Serum samples were analyzed for total calcium and alkaline phosphatase. Calcium, hydroxyproline, and collagen crosslinks (HPLC) were determined in urine. After fluorochrome double labeling, the rats were sacrificed four months postsurgery and the first lumbar vertebrae and the proximal tibiae were processed undecalcified for bone histomorphometry. Ovariectomy induced a 28% and a 69% reduction in vertebral and tibial cancellous bone area, respectively. Osteopenia in OVX rats was associated with increased histomorphometric and biochemical indices of bone turnover. The administration of 1,24,25(OH)3D3 to OVX rats dose-dependently increased vertebral and tibial cancellous bone mass, serum calcium, and urinary calcium excretion, and reduced histomorphometric and biochemical indices of bone resorption. 1,24,25(OH)3D3 at doses of 0. 2 and 0.3 microg/kg/day produced strong anabolic effects, especially on vertebral cancellous bone in OVX rats, and increased mineral apposition rate and wall width of completed remodeling units relative to vehicle-treated OVX rats. Even at high doses, 1,24, 25(OH)3D3 did not impair bone mineralization. We conclude that oral administration of 1,24,25(OH)3D3 can effectively prevent estrogen depletion-induced cancellous bone osteopenia in the aged OVX rat model. The therapeutic window for 1,24,25(OH)3D3 in OVX rats, however, is also narrow, comparable to that for calcitriol.
...
PMID:Prophylactic effects of 1,24,25-trihydroxyvitamin D3 on ovariectomy-induced cancellous bone loss in the rat. 911 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---