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)

Prolonged chronic inflammation and corticosteroid therapy increase the risk of osteoporosis in patients with Crohn's disease. It has been estimated that 30% of these patients, who take steroids for prolonged periods, will suffer a vertebral fracture. Patients with Crohn's disease are difficult to wean from corticosteroids and therefore are at risk of developing bone complications. The purpose of this cross-sectional study was to examine the relationship between cumulative steroid dose, duration of the disease and the development of osteopenia in patients with Crohn's disease. We studied 28 patients (17 men, 11 women) with Crohn's disease: eight had one or more bowel resections and all the women were premenopausal. Serum calcium, phosphate, total alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), 25(OH)Vitamin D(3) and 1,25 (OH)(2) Vitamin D(3) were measured by autoanalyser methods or radioimmunoassay. Bone mineral density (BMD) was studied using dual energy X-ray bone absorptiometry of the lumbar spine (L2-L4) and the femoral neck. Of these 28 patients, 27 received an average of 17.3 +/- 21.7 g (range 1 to 80) g of prednisone over a period of 4 to 216 months. Fourteen out of the 28 patients had mildly diminished bone density (z-score >-2.5 SD and < -1 SD) of the spine and 15/28 of the hip. We found a greater decrease in bone density (z-score < -2.5 SD) in 2 out of 28 patients at the spine and in 5 out of 28 at the femoral neck. Those in whom the duration of the disease was less than two years (12 patients) had significantly higher vertebral z-scores (-0.096 +/-0.91) than those who had the disease for over two years (-1.31 +/- 2.37), (p<0.05). We found no significant correlation between lumbar spine and femoral neck z-scores and cumulative steroid therapy. Six out of 28 patients (four women and two men), of mean age 47.2+/-11.7, had one vertebral fracture. The mean cumulative dose of steroids (prednisone or budesonide) in patients with vertebral fractures was higher but not significantly different from that in patients without fractures -20.1+/-18.2 versus 14.1+/-11.2 g of prednisone, respectively (p>0.05). No correlation was found between various serum hormones and other biochemical parameters of bone turnover or bone density. We conclude that a large proportion of patients with Crohn's disease have reduced bone mineral density (58% at the spine and 75% at the femoral neck). The pathogenesis of bone loss is probably multifactorial. Although steroid therapy might be an important contributory factor, we were unable to find a significant correlation between it and bone loss. On the contrary, we observed that the duration of the disease makes a significant contribution to bone loss.
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PMID:Negative impact of Crohn's disease on bone mineral mass. 1575 48

A case-control study was undertaken to understand the etiopathology of the bone deformities among young children in a fluoride-affected village of the Bihar State. Two villages were selected: one village with high fluoride in drinking water (7.9 +/- 4.15 ppm), and the other village with normal levels of fluoride (0.6 +/- 0.31 ppm) as the control village. The source of drinking water was bore wells in both the villages. Two hundred and forty subjects from 54 households (HHs) of the high-fluoride village (HFV) and 1443 subjects from 197 HHs of the control village were selected for the study. Dental mottling (DM) was observed in 50% and skeletal deformities of various forms were observed in 20% of the total population of HFV, whereas, in the control village, DM was 6% and skeletal deformities were absent. The prevalence of both, DM and skeletal deformities was high in the younger age group of 1.5 to 14 years. Genu valgum, genu varum, bowing of tibia, saber shin, and widening of the lower ends of long bones at the wrist were the typical skeletal deformities observed among affected children in the HFV. X-rays of the children with deformities revealed varying degrees of bending of bones and enlargement of epiphyseal ends of metaphyses with fraying of bone and ligamental calcification. A survey indicated significantly low calcium and high phosphorus intake among the population of the HFV as compared to that of the control village, possibly resulting from low intake of milk and high intake of potatoes, respectively. The mean urinary fluoride level was significantly higher in the children of the HPV, both with and without deformities, as compared to that of the control village. The mean serum 25 OHD3 (25 Hydroxy Vitamin D) and calcium levels were significantly lower and alkaline phosphatase activity was significantly higher among the children with deformities as compared to those without deformities from the HFV and the control village. Serum intact parathyroid hormone (IPTH) levels were high in children both with and without deformities in the HFV as compared to those in the control village. No significant differences were observed in the concentration of serum and urinary creatinine, and Cu, and Mg levels between the HFV and the control village. It can be concluded that some of the children from the HFV manifested severe bone deformities (rickets), which were confirmed by the existence of low serum calcium and vitamin D levels.
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PMID:Severe bone deformities in young children from vitamin D deficiency and fluorosis in Bihar-India. 1589 80

Studies performed in the Northern Hemisphere and in areas distant from the equator have demonstrated significant seasonal variation in 25-hydroxyvitamin D (25OHD) levels. Whether such variation occurs in a subtropical area such as Australasia is not clear. We performed a cross-sectional study of 1,606 healthy, postmenopausal women recruited over a 33-month period. The study had three goals: to determine the normal levels of 25OHD in healthy postmenopausal women living in Auckland, New Zealand; to determine whether seasonal variation of 25OHD occurs at this latitude; to assess the relationship between 25OHD, biochemical indices, anthropometric variables and bone mineral density (BMD). We found significant seasonal variation in 25OHD levels, with the change in monthly ultraviolet dose from summer to winter being followed 6-8 weeks later by a corresponding change in 25OHD levels. Vitamin D insufficiency (25OHD <50 nmol/l) was common. During summer, 28-58% of participants had suboptimal vitamin D status, while in winter, the frequency increased to 56-74%. 25OHD levels correlated with participants' age (r=-0.15), weight (r=-0.11), body mass index (r=-0.13), fat mass (r=-0.14), percentage body fat (r=-0.16), physical activity (r=0.10) and the month of blood sampling (all P<0.0001). Collectively, age, fat mass, physical activity, and month of sampling explained 21% of the variance in 25OHD. No significant relationships were noted between 25OHD and BMD at any site. Other variables that showed significant monthly variation were glucose (P=0.002), serum phosphate, alkaline phosphatase, and albumin (all P<0.0001). There was no monthly variation in BMD at the lumbar spine or proximal femur. In conclusion, there is significant seasonal variation in 25OHD levels, even in a subtropical climate. Furthermore, despite generous amounts of sunlight, considerable numbers of women have suboptimal vitamin D status, even in summer. Our findings support the suggestion that vitamin D supplementation should become standard practice in this population of women, particularly during winter.
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PMID:Determinants of vitamin D status in older women living in a subtropical climate. 1602 59

The Vitamin D binding protein (DBP) is a multifunctional plasma protein that can significantly enhance the chemotactic response to complement fragment C5a. The chemotactic cofactor function of DBP requires cell surface binding in order to mediate this process. The goal of this study was to investigate the effect of ligating DBP with its two primary physiological ligands, Vitamin D and G-actin, on both binding to neutrophils and the ability to enhance chemotaxis to C5a. There was no difference in neutrophil binding between of the holo (bound) forms versus the apo (unbound) form of radioiodinated DBP, indicating that the cell binding region of DBP is likely distinct from the Vitamin D sterol and G-actin binding sites. Likewise, G-actin, 25(OH)D3, and G-actin plus 25(OH)D3 bound to DBP did not alter its capacity to enhance chemotaxis toward C5a. However, the active form of Vitamin D (1,25(OH)2D3) completely eliminated the chemotactic cofactor function of DBP. Dose-response curves demonstrated that as little as 1pM 1,25(OH)2D3 significantly inhibited chemotaxis enhancement. Moreover, at physiological concentrations 1,25(OH)2D3 needs to be bound to DBP to mediate the inhibitory effect. Neutrophil chemotaxis to optimal concentrations of C5a, formyl peptide, CXCL8 or leukotriene B4 was not altered by 1,25(OH)2D3, indicating that the active vitamin does not have a global inhibitory effect on neutrophil chemotaxis. Finally, inhibition of cell surface alkaline phosphatase (AP) with sodium orthovanadate completely reversed the inhibitory effect of 1,25(OH)2D3. These results indicate that the cell binding and co-chemotactic functions of DBP are not altered when the protein binds G-actin and/or Vitamin D. Furthermore, the co-chemotactic signal from DBP can be eliminated or counteracted by 1,25(OH)2D3.
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PMID:Selective inhibition of the C5a chemotactic cofactor function of the vitamin D binding protein by 1,25(OH)2 vitamin D3. 1611 86

To determine the proportion of vitamin D insufficiency in 6- to 10-year-old preadolescent African-American children residing in Pittsburgh, Pennsylvania and to estimate their therapeutic response to vitamin D 400 IU/day for 1-month, an open-label pre- and post-comparison of vitamin D status following vitamin D 400 IU daily for 1 month during winter and early spring was conducted. Outcomes included serum calcium, phosphorus, albumin, 25 hydroxyvitamin D [25 (OH) D], 1, 25 dihydroxyvitamin D [1, 25 (OH) (2) D], parathyroid hormone (PTH), and markers of bone turnover (serum bone-specific alkaline phosphatase, osteocalcin, and urine n-telopeptide crosslinked collagen type 1 [NTX]). Dietary intake of vitamin D was assessed using a food frequency questionnaire. Forty-one of the 42 enrolled subjects (mean age: 8.9 +/- 1.2 yrs [SD]) were analyzed, and 20/41 (49%) were vitamin D insufficient. Vitamin D insufficient group had a suggestive trend of being older (9.2 +/- 1.0 years vs. 8.5 +/- 1.3 years, p = 0.06) and more pubertally advanced (Tanner II: 7/20 vs. Tanner II: 1/21, p = 0.02). Mean dietary intake of vitamin D was 277 ( 146 IU/day (n = 41). Adequate intake for vitamin D (200 IU/day) was not met in 16/41 (39%); however, the dietary intake of vitamin D was not significantly different between the vitamin D insufficient and vitamin D sufficient groups.
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PMID:Vitamin D insufficiency in preadolescent African-American children. 1621 Nov 92

Steroid treatment has several side effects, including the deterioration of the bone and mineral metabolism in children with nephrotic syndrome. This randomized prospective study was conducted to determine the effects and prophylactic role of calcium plus vitamin D treatment on bone and mineral metabolism in children receiving prednisolone treatment. 40 children (27 boys and 13 girls) with NS (18 new onset and 22 relapsing) were included in the study. Their mean age was 4.6+/-1.8 years. All patients received prednisolone treatment (2 mg/kg/day for 4 weeks followed by alternate days at the same dose for 4 weeks). The patients were randomized into treatment (vitamin D 400 IU plus calcium 1 g daily) and non-treatment groups. Bone mineral density, serum Ca, P, alkaline phosphatase and urinary Ca and P excretions were analyzed at the beginning and 2 months after the treatment. The XR36 Norland device was used for bone mineral density analysis. Bone mineral density was significantly decreased in both the treatment (0.54+/-0.15 to 0.51+/-0.1 g/cm(2), P =0.001) and non-treatment (0.52+/-0.18 to 0.45+/-0.16 g/cm(2), P <0.001) group. But the percentage of bone mineral density decrease was found to be significantly lower in the treatment group than in the non-treatment group (4.6+/-2.1% vs. 13.0+/-4.0%, respectively; P <0.001). Serum calcium and urinary calcium excretion increased in the treatment group (8.0+/-1.0 to 10.0+/-0.5 mg/dl and 1.1+/-0.5 to 3.2+/-1.0 mg/kg/day) and non-treatment group (8.1+/-0.8 to 10.0+/-0.6 mg/dl and 1.4+/-0.9 to 3.8+/-3.3 mg/kg/day) after prednisolone treatment (P <0.001). Steroid treatment decreases bone mineral density in children with nephrotic syndrome. Vitamin D plus calcium therapy at the current doses reduces but does not completely prevent bone loss, with no additional adverse effects.
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PMID:Prophylactic calcium and vitamin D treatments in steroid-treated children with nephrotic syndrome. 1638 19

The present cross-sectional study was designed to evaluate the vitamin D status in three groups of women in Bangladesh by using serum 25-hydroxyvitamin D (S-25-OHD), alkaline phosphatase (S-ALP), calcium (S-Ca) and phosphate (S-P). Sampling was undertaken at three locations in the city of Dhaka, Bangladesh. Representative subjects of three groups of women aged 18-60 years were studied. Study subjects included nonveiled young women = group A (N = 36, mean+/- SD age 22.3 +/- 1.9 years), veiled women =group B (N = 30, mean+/- SD age 47.7+/- 9.4 years) and nonveiled diabetic women = group C (N = 55, mean +/- SD age 50.2 +/- 5.9 years). The mean value of S-25-OHD was not significantly different in the groups. The distribution of S-25-OHD concentration in all groups was shifted overall toward the lower limit of the normal range. Vitamin D deficiency (serum 25-OHD level <25 nmol/l) was detected in 39% of young women (university students), 30% in veiled women and 38% in diabetic women, respectively. Vitamin D insufficiency defined as serum 25-OHD concentration <40 nmol/l was detected in 78% of group A, 83% in group B and 76% in group C, respectively. As indicated, prevalence of vitamin D insufficiency was a bit higher in group B compared with the other groups studied although it was not statistically significant (P > 0.05). In the present study, there were several independent predictors of serum 25-OHD, i.e. both increasing parity (r = 0.286; P < 0.005) and increasing time spent outdoors (r = 0.515; P < 0.001) were associated with significant increase in serum 25-OHD. A strongly significant inverse correlation between serum ALP and 25-OHD (r = -0.303;P<0.001) was observed. The results showed that women in Bangladesh, regardless of different age-groups, lifestyle and clothing, were at risk of developing hypovitaminosis D. The results emphasize the appropriate health message for vitamin D needs in Bangladeshi women, since vitamin D insufficiency significantly affects bone integrity.
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PMID:Hypovitaminosis D is common in both veiled and nonveiled Bangladeshi women. 1650 Aug 82

Vitamin D (Vit D) is an essential element for the regulation of serum calcium, phosphate, and alkaline phosphatase (Alk Ph). Because the Vit D serum level is not usually measured directly, Vit D deficiency is diagnosed indirectly by changes in serum calcium, phosphate, and Alk Ph leves. The current study assessed the status of these biochemical parameters in subjects with different degrees of Vit D deficiency. We selected 1,210 subjects, between 20 and 69 years old, randomly from the Tehran population. Subjects with diseases or medications that modified bone metabolism were excluded from the study. Serum 25(OH) D, calcium, phosphate, Alk Ph, and parathyroid hormone (PTH) levels were measured and the status of these biochemical parameters was compared in subjects with different degrees of Vit D deficiency. Vit D deficiency was diagnosed in 79.6% of the subjects. Different degrees of Vit D deficiency were classified as follows: group 1, severe; group 2, moderate; and group 3, mild. Serum PTH levels in the Vit D-deficient groups were significantly higher than that in group 4 (normal Vit D). Serum calcium and phosphate levels in groups 1 and 2 were significantly lower than those in groups 3 and 4. No significant difference was seen in serum Alk Ph in the groups with different degrees of Vit D deficiency. The sensivity for at least one biochemical variable (calcium, phosphorus, or Alk Ph) for the detection of severe, moderate, and mild Vit D deficiency was 24.2%, 13.8%, and 6%, respectively. When the serum 25(OH) D level was reduced to less than 25 nmol/l (groups 1 and 2), the effects of Vit D deficiency on calcium and phosphate levels were obvious. Therefore, the usual biochemical parameters (calcium, phosphate, Alk Ph) alone do not have sufficient sensitivity to detect mild deficiency of Vit D.
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PMID:The status of biochemical parameters in varying degrees of vitamin D deficiency. 1662 34

Vitamin D plays a major role in the regulation of mineral homeostasis and affects bone metabolism. So far, detailed knowledge on the vitamin D endocrine system in human bone cells is limited. Here we investigated the direct effects of 1alpha,25-(OH)2D3 on osteoblast differentiation and mineralization. Also, we studied the impact of 24-hydroxylation, generally considered as the first step in the degradation pathway of vitamin D, as well as the role of the nuclear and presumed membrane vitamin D receptor (VDR). For this we used a human osteoblast cell line (SV-HFO) that has the potency to differentiate during culture forming a mineralized extracellular matrix in a 3-week period. Transcriptional analyses demonstrated that both 1alpha,25-(OH)2D3 and the 24-hydroxylated metabolites 24R,25-(OH)2D3 and 1alpha,24R,25-(OH)3D3 induced gene transcription. All metabolites dose-dependently increased alkaline phosphatase (ALP) activity and osteocalcin (OC) production (protein and RNA), and directly enhanced mineralization. 1Alpha,24R,25-(OH)3D3 stimulated ALP activity and OC production most potently, while for mineralization it was equipotent to 1alpha,25-(OH)2D3. The nuclear VDR antagonist ZK159222 almost completely blocked the effects of all metabolites. Interestingly, 1beta,25-(OH)2D3, an inhibitor of membrane effects of 1alpha,25-(OH)2D3 in the intestine, induced gene transcription and increased ALP activity, OC expression and mineralization. In conclusion, not only 1alpha,25-(OH)2D3, but also the presumed 24-hydroxylated "degradation" products stimulate differentiation of human osteoblasts. 1Alpha,25-(OH)2D3 as well as the 24-hydroxylated metabolites directly enhance mineralization, with the nuclear VDR playing a central role. The intestinal antagonist 1beta,25-(OH)2D3 acts in bone as an agonist and directly stimulates mineralization in a nuclear VDR-dependent way.
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PMID:Evidence that both 1alpha,25-dihydroxyvitamin D3 and 24-hydroxylated D3 enhance human osteoblast differentiation and mineralization. 1674 65

Osteoblast maturation is partly controlled by the interaction of 1alpha,25(OH)(2)D(3) (D3), an active metabolite of Vitamin D, with other growth factors. The first reports describing the in vitro effect of D3 on human osteoblast differentiation performed experiments in the presence of serum. One potentially exciting candidate that might help explain the D3 responses observed for osteoblasts cultured with serum is lysophosphatidic acid (LPA). Drawn to the possibility that D3 and serum borne LPA might interact to induce osteoblast maturation we co-treated human cells with D3 and serum in the presence of Ki16425, an LPA receptor antagonist. Ki16425 inhibited osteoblast maturation as determined by markedly reduced alkaline phosphatase (ALP) expression. We subsequently found that LPA and D3 acted synergistically in generating mature osteoblasts and that this differentiation response could be inhibited using pertussis toxin, implying an important role of Galphai signal transduction. Furthermore, we found evidence for a dependency on both mitogen activated protein kinase kinase (MEK) and Rho associated coiled kinase (ROCK) for LPA and D3 stimulated maturation.
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PMID:Lysophosphatidic acid cooperates with 1alpha,25(OH)2D3 in stimulating human MG63 osteoblast maturation. 1684 86


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