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)

In 27 patients on periodic haemodialysis, serum levels of alkaline phosphatase (ALP), osteocalcin (BGP), intact parathyroid hormone (PTHi) and its two fragments, terminal COOH (PTH-Cter) and middle molecule (PTH-MM), and procollagen type 1 carboxy-terminal extension peptide (P1CP) were measured. The same patients underwent radiography of the skull and of the hands, ultrasonography of the parathyroids and scintigraphy of the skeleton with 99mTc-MDP. The study was completed by the measurement of aluminium (Al) in the blood and the deferoxamine test (DFO). Two groups of patients emerged, one (group A, n = 14) with PTHi greatly increased (201.07 +/- 109.72 pg/mL) and the other (group B, n = 13) with values within the normal range (32.69 +/- 17.06 pg/mL) (p < 0.001). In group A, ALP, BGP and particularly P1CP were increased with a statistically significant difference compared to group B. Specific radiographic alterations were found in 12 patients of group A; 7 patients also had hypertrophy of the parathyroids. There was no difference in the scintigraphic alterations of the skeleton between the two groups. The authors conclude that it is the association of the high values of PTHi with those of the markers of bone metabolism, the normal level of Al, the negativity of the DFO test and the radiological alterations which together allow the diagnosis of renal osteodystrophy with hyperparathyroidism.
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PMID:Renal osteodystrophy with hyperparathyroidism: the diagnostic value of intact parathormone, alkaline phosphatase, osteocalcin and procollagen. 786 45

Serum intact PTH [1-84] levels were evaluated as a potential non-invasive method for the diagnosis of renal osteodystrophy in children treated with CAPD/CCPD. Sixty-eight bone biopsy samples were obtained from 55 patients, aged 13 +/- 5 (X +/- SD) years, undergoing CAPD/CCPD for 29 +/- 13 months; osteitis fibrosa was present in 34 cases, mild lesions of secondary hyperparathyroidism in six, 15 had adynamic lesions, and 13 were classified as normal histology. Serum calcium levels were higher in patients with adynamic bone or normal bone histology than in those with secondary hyperparathyroidism, whereas serum phosphorus, alkaline phosphatase and PTH levels were greater in patients with osteitis fibrosa. The combination of a serum PTH level > 200 pg/ml and a serum calcium value < 10 mg/dl was 85% sensitive and 100% specific for identifying patients with high-turnover lesions of bone. Serum PTH values < 200 pg/ml were 100% sensitive but only 79% specific for patients with adynamic bone; specificity increased to 92%, however, using the combined criteria of a PTH level < 150 pg/ml and a serum calcium level > 10 mg/dl. Higher serum calcium levels and serum PTH values within or below the normal range characterize patients with the adynamic lesion of renal osteodystrophy. Serum PTH levels of approximately 200 pg/ml are useful for distinguishing patients with low-turnover lesions of renal osteodystrophy from those with secondary hyperparathyroidism.
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PMID:Biochemical markers of renal osteodystrophy in pediatric patients undergoing CAPD/CCPD. 812 16

During the course of chronic renal failure (CRF) in man, renal osteodystrophy (osteitis fibrosa and/or osteomalacia) gradually develops. The present study aimed to establish a similar type of CRF leading to renal osteodystrophy in rats. During progressive CRF development over 225 days after 5/6 nephrectomy, the following serum variables were measured: creatinine, immunoreactive parathyroid hormone (iPTH), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), a25-hydroxyvitamin D3, (25(OH)D3), alkaline phosphatase, albumin, phosphate, urea nitrogen, total calcium, and other blood electrolytes. Subsequent to sacrifice, mechanical properties of the rat femur, bone histomorphometry (osteoid and eroded surfaces) and bone contents of calcium, phosphate and hydroxyproline were also examined. Serum creatinine in rats with CRF gradually escalated by some 70%, while circulating 1,25(OH)2D3 was reduced beneath detection level. Total plasma calcium and phosphate concentrations were, however, almost unchanged indicating that PTH-induced bone remodeling due to moderate hyperparathyroidism sustained calcium homeostasis. Alkaline phosphatase levels were reduced by some 50%, which reflects chronically impeded bone formation. Bone histomorphometry assessment revealed substantial elevation of resorption with moderate accompanying fibrosis in about 70% of afflicted animals. Bone calcium, phosphate and hydroxypyrroline contents remained unaltered. However, hydroxyproline/calcium ratio was marginally reduced. These results, together with altered mechanical bending stress characteristics and diminished diaphysis cross section area, confirm development of mixed bone lesions in the uremic animals. Our results are compatible with the early development of CRF in man. The established rat model is therefore useful in elucidating the precipitation and early treatment of renal osteodystrophy in humans.
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PMID:Surgically induced uremia in rats. I: Effect on bone strength and metabolism. 814 13

The mechanism of crystal deposition in joints varies with the chemical nature of the crystal. Crystallisation of monosodium urate, characteristic of gout, requires a neutral pH and supersatured tissues, which is the basis for the clinical definition of the upper limit of normal blood uric acid level. The appearance of crystals also is dependent on time since crystallisation of monosodium urate is very slow. Inhibitory or promoting factors could intervene and explain rare cases of gout without hyperuricemia or the rapid crystallisation which seems to characterise some types of drug-induced gout. Crystal deposits of calcium pyrophosphate dihydrate form mainly in the cartilage where they seem favoured by ageing or by trauma, which could deplete cartilage of crystallisation inhibitors, notably proteoglycans. High pyrophosphate levels within cartilage also play an important role. The appearance of these pyrophosphates in the interstitial cartilagenous medium would be in large part due to the activity of an ectoenzyme, nucleoside triphosphate pyrophosphatase; increased activity of this ectoenzyme could be responsible for some chondrocalcinosis. Chronic hypercalcaemia can also be involved in the pathogenesis of cartilage deposition of calcium pyrophosphate dihydrate by raising the calcium-pyrophosphate product, or by decreasing the activity of alkaline phosphatase, an enzyme responsible for breakdown of extracellular pyrophosphates. The pathophysiology of calcium phosphate deposits is poorly understood. For some authors, these deposits occur within matrix vesicles, but for others, within collagen fibres. Increase in the calcium-phosphate product can also be a cause, for example, during renal osteodystrophy or vitamin D intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mechanism of crystal deposition in the joints]. 817 67

We analyzed transiliac bone biopsy specimens from 30 end-stage renal failure patients, taken at the time of admission for CAPD training. Results were compared with values of iPTH, bone alkaline phosphatase, 1,25-dihydroxyvitamin D3, skeletal survey, quantitative computed tomography (QCT) and single photon absorptiometry (SPA) bone density measurements. Osteitis fibrosa was the most common histological diagnosis, present in 15 of the 30 patients (50%), with eight classified as "severe" and seven as "mild." Eight patients (27%) had adynamic bone lesion, four mixed renal osteodystrophy (13%), and two (7%) osteomalacia. The mean age of the adynamic group was higher than the osteitis fibrosa group (41 +/- 12.1 vs. 56 +/- 10.2 years; P < 0.01), and than the mixed group (39 +/- 7.5 vs. 56 +/- 10.2 years; P < 0.02). Levels of iPTH enabled discrimination between groups, but not between individual patients, and values correlated with bone alkaline phosphatase (r = 0.62; P < 0.001). Erosion of the terminal phalanges was seen on the plain X-rays of 7 of 15 patients with mild or severe OF, and in three patients with another diagnosis. The majority of patients (> 90%) had bone density measurements within the normal range. No significant correlation existed between QCT or SPA scores and any of the histomorphometric parameters, or iPTH. We conclude that iPTH is the most helpful non-invasive investigation in this group of patients. Plain X-ray of the hands is the most useful radiological investigation, but single measurements of bone density are not diagnostic.
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PMID:Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease. 826 37

Hydroxyproline (HYP) is an amino acid which is highly specific for bone collagen. Measurement of HYP provides an index of bone resorption, although the usefulness in this respect of the serum free HYP, which is the easiest HYP fraction to determine, has not yet been established. In the present study, the serum free HYP was measured using the method of Dabev et al., and the data were compared against other parameters of renal osteodystrophy (ROD). In comparison with values for the normal control group (n = 10), the serum free HYP was significantly elevated in the patient group with conservatively treated end-stage renal failure (n = 14) and in the patient group on chronic hemodialysis (n = 107), with the latter group showing the highest value. Also, in the group with radiographic evidence of bone resorption, the free HYP exhibited a significant elevation. Significant positive correlations were noted between the free HYP and both the parathyroid hormone (PTH) and alkaline phosphatase (Al-P) levels. When the subjects undergoing bone biopsy were divided according to their histological findings into an increased osteoid group and an increased osteoid + resorption group, the latter displayed a significantly higher free HYP value. In addition, the free HYP values were low in the group administered 1 alpha-OH-D3 and showing only slight bone resorption. These results suggest that since the free HYP closely reflects accelerated bone resorption in ROD and is easier to measure than non-protein-bound HYP, it can serve as a clinically useful index of ROD.
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PMID:Reevaluation of the usefulness of serum free hydroxyproline as a parameter for assessing renal osteodystrophy. 833

In order to know the pattern of renal osteodystrophy in haemodialysis patients in Saudi Arabia we conducted a multicentre study involving 209 patients. The mean age of the patients was 39.4 +/- 14 (18-70) years, 128 were males and 81 females. All patients were on acetate dialysate and their mean duration on dialysis was 3.5 +/- 1.5 years. The major symptom was bone and joint pain (25.8%). The mean serum calcium was 2.1 +/- 0.26 mmol/l, phosphorus 2.0 +/- 0.36 mmol/l, alkaline phosphatase 19.7 +/- 14.6 u/l and parathyroid hormone level was 8.9 +/- 3.9 mg/ml. The mean serum aluminium (AL) level was 25.4 +/- 17.7 micrograms/l, while that of 1,25 vitamin D3 was 8.1 +/- 4.2 ng/l and of fluoride was 92.2 +/- 31.4 micrograms/l. The major radiological finding was osteosclerosis (70%). Dual-photon absorptiometry (DPA) showed low bone mineral density (LBM) in 65% of the patients. Forty-one patients had bone biopsies with AL staining of the biopsies. Of this group, 92% had changes of hyperparathyroidism and 66% of them were pure hyperparathyroidism. Sixty percent of them had variable degrees of AL intoxication. The radiological skeletal survey of those patients could detect abnormalities in only 46% while 70% of them had abnormal bone mineral density (BMD). In conclusion, osteosclerosis is the commonest radiological finding in our dialysis patients while secondary hyperparathyroidism is the main histopathological diagnosis in bone biopsy, even in patients with normal skeletal survey. AL intoxication is a significant problem in our population. DPA is more sensitive in detecting bone abnormalities than X-radiography.
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PMID:Pattern of renal osteodystrophy in haemodialysis patients in Saudi Arabia. 839 43

Procollagen-I carboxylterminal extension peptide (PICP) was determined in the serum and dialysate of 26 continuous ambulatory peritoneal dialysis (CAPD) patients and in the serum of 11 healthy controls. PICP serum levels were significantly higher in CAPD patients than in healthy controls (p < 0.001). There was no correlation between serum PICP levels and those of calcium, phosphorus, magnesium, alkaline phosphatase, osteocalcin, and intact parathyroid hormone (iPTH). Serum and dialysate levels of osteocalcin and iPTH showed a significant correlation (p < 0.001). The dialysate-to-serum PICP ratio in 21 patients was lower than 1.0. In the remaining 5 patients, however, the above ratio was higher than 1.0. We conclude that in CAPD patients serum PICP levels do not correlate with biochemical parameters of renal osteodystrophy. A dialysate-to-serum PICP ratio above 1.0 could implicate an increased local peritoneal fibroblastic activity and could be a useful marker of peritoneal fibrosis in CAPD.
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PMID:Procollagen type-I in the serum and dialysate of continuous ambulatory peritoneal dialysis patients. 839 46

We evaluated the bone metabolic activity in patients with renal osteodystrophy using positron emission tomography and [18F]fluoride ion. Eight patients had secondary hyperparathyroidism (HPT), and three had low-turnover bone disease. Eleven normal subjects were also studied, and three of the eight HPT patients were reevaluated after therapy. A rate constant (K) describing the net transport of [18F] fluoride ion into a bound compartment in bone was calculated using both a three-compartment model and Patlak graphical analysis. Values of K were compared with biochemical data and with histomorphometric indices. The results indicate that K is significantly higher (P < 0.01) in HPT patients than in normal subjects and patients with low-turnover bone disease. Values of K correlated with serum alkaline phosphatase (r = 0.81) and PTH (r = 0.93) levels and with histomorphometric indices of bone formation rate (r = 0.84, P < 0.01) and eroded perimeter (r = 0.77, P < 0.05). Values of K decreased by 40 and 30%, respectively, in two patients who underwent parathyroidectomy and medical therapy. Positron emission tomography studies of bone using [18F]fluoride ion can differentiate low turnover from high turnover lesions of renal osteodystrophy and provide quantitative estimates of bone cell activity that correlate with histomorphometric data.
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PMID:Bone metabolic activity measured with positron emission tomography and [18F]fluoride ion in renal osteodystrophy: correlation with bone histomorphometry. 840 70

A 6-month protocol of oral pulse calcitriol was used in nine uraemic children (2-14 years old) on dialysis who presented with renal osteodystrophy. Calcitriol was administered twice a week, 4 micrograms per dose for patients over 30 kg and 3 micrograms for patients less than 30 kg. Plasma levels of parathyroid hormone, calcium, phosphorus and alkaline phosphatase were carefully controlled during the study. Parathyroid hormone levels decreased by 68% and 56% by the 2nd and 6th months of treatment in seven patients, while they remained unchanged in two patients with focal segmental glomerulosclerosis and massive proteinuria. Eight hypercalcaemic episodes from 77 determinations were observed, all of them recovered after 1 week of vitamin D withdrawal. We conclude that oral calcitriol pulse therapy is a good alternative for renal osteodystrophy in uraemic children. Careful monitoring of plasma parathyroid hormone and calcium is needed during follow-up when using this approach in paediatric patients.
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PMID:Calcitriol oral pulse therapy in children with renal osteodystrophy. 858 20


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