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

Chondrocalcinosis is known to be common in hyperparathyroidism. In order to discover the effect of parathyroidectomy on chondrocalcinosis and to investigate this association further, we studied two groups of patients. In one group were 41 postparathyroidectomy patients, and in the other 100 admissions to the acute geriatric unit. The total incidence of chondrocalcinosis in the parathyroidectomy group was 32%, and in the elderly control group 11%. There was little or no osteoarthrosis in these patients. It was found that chondrocalcinosis occurred in the normal population from the age of 75 and in the hyperparathyroid group from the age of 45. In both groups the incidence rose steadily with age. In the hyperparathyroid group alone, preoperative serum calcium levels were no different in those without chondrocalcinosis, suggesting that hypercalcaemia alone is not a sufficient stimulus for chondrocalcinosis. Those with chondrocalcinosis had higher mean preoperative alkaline phosphatase levels, nearly twice as much radiological bone disease, and were older. Parathyroidectomy had no effect on attacks of pseudogout or on preexisting cartilage calcification. A connection with high levels of circulating parathyroid hormone is suggested, and a link with physical age-related changes in cartilage postulated.
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PMID:Chondrocalcinosis in primary hyperparathyroidism. Influence of age, metabolic bone disease, and parathyroidectomy. 85 41

Osteoarthritis or 'Joint Failure' is a multi-factorial disease with a final common pathway of cartilage degeneration and bone eburnation. The association of arthritic disease and joint degeneration with the deposition of sodium urate crystals in gout and calcium pyrophosphate crystals in pseudogout (chondrocalcinosis) is clinically well established. Electron microscopy coupled with electron probe analysis has revealed the presence of various other calcium phosphate crystals in joint tissues and fluids. We have found three new morphological types of apatite crystals in human articular cartilage which are too small to be detected by X-rays of human joints or even by light microscopy of joint tissues. Two morphologically distinct types of apatite crystals in articular cartilage are associated with extracellular matrix vesicles formed from the cell processes of chondrocytes. 'Cuboid' crystals, which are found in the pericellular regions near the surface zone of articular cartilage, appear to be a variant of apatite and may even be 'Whitlockite' because there are traces of magnesium present. There are increased numbers of these microscopic 'cuboid' crystals (Type II) and Mineral Nodules (Type I) in arthritic cartilage and this is coupled with increased numbers of matrix vesicles and alkaline phosphatase activity. Clusters of fine needle-shaped apatite crystals (Type III) found on the surface of articular cartilage are not associated with matrix vesicles. Thus some forms of osteoarthritis are closely associated with apatite type crystal deposition and may imply abnormal mineral formation in articular cartilage as a pathogenic mechanism.
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PMID:Apatite-type crystal deposition in arthritic cartilage. 409 1

A case of pseudogout associated with low values of magnesium and alkaline phosphatase activity in the synovial fluid is presented. The low magnesium concentration is believed to cause the low alkaline phosphatase activity, since adding magnesium in vitro raised the activity to normal. The reason for the low magnesium concentration in the synovial fluid remains unclear.
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PMID:Pseudogout with low values of magnesium and low alkaline phosphatase activity in synovial fluid. 664 23

Chronic crystal-associated arthropathies such as gout and pseudogout can lead to local bone destruction. Because osteoblasts, which orchestrate bone remodeling via soluble factors and cell-to-cell interactions, have been described in contact with microcrystals, particularly in uratic foci of gout, we hypothesized that microcrystals of monosodium urate monohydrate (MSUM) and of calcium pyrophosphate dihydrate (CPPD) could alter osteoblastic functions. MSUM and CPPD adhered to human osteoblastic cells (hOB) in vitro and were partly phagocytized as shown by scanning electron microscopy. MSUM and CPPD dose-dependently stimulated the production of PGE(2) in hOB as assessed by enzyme immunoassay, a response that was synergistically enhanced in the presence of IL-1. The mechanism of this synergism was, at least in part, at the level of the expression of cyclooxygenase-2 as evaluated by immunoblot analysis. MSUM and CPPD also stimulated the expression of IL-6 and IL-8 and reduced the 1,25-dihydroxyvitamin D(3)-induced activity of alkaline phosphatase and osteocalcin in hOB (with no synergism with IL-1). MSUM- or CPPD-stimulated expression of IL-6 in hOB pretreated with the selective cyclooxygenase-2 inhibitor NS-398 was increased, unlike that induced by IL-1 alone which was partially reduced. MSUM-, CPPD- or IL-1-induced expression of IL-8 was unchanged by pretreating hOB with NS-398. These results suggest that inflammatory microcrystals alter the normal phenotype of hOB, redirecting them toward reduced bone formation and amplified osteoblast-mediated bone resorption, abnormalities that could play a role in the bone destruction associated with chronic crystal-induced arthritis.
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PMID:Inflammatory microcrystals alter the functional phenotype of human osteoblast-like cells in vitro: synergism with IL-1 to overexpress cyclooxygenase-2. 1199 89

To evaluate renal osteodystrophy (ROD), bone biopsies were performed in 57 patients with end-stage renal failure (ESRF) on dialysis, 46 on hemodialysis (HD) and 11 on peritoneal dialysis (PD). There were 29 males (mean age of 42 years) and 28 females (mean age of 39 years). Relevant presenting clinical features were pruritus in 46 cases, bone pains in 32, acute pseudogout in three, bone deformities in two, conjunctiva! calcification in two, cutaneous calcification in two, and corneal calcification in one. The mean value of predialysis blood investigations were as follows: urea 33.9 mmol/L, creatinine 913 umol/L, bicarbonate 18 mmol/L, calcium 2.36 mmol/L, albumin 40 g/L, phosphorus 1.69 mmol/L, alkaline phosphatase 178 U/L, parathyroid hormone 543 pmol/L, magnesium 1.06 mmol/L and aluminum 1.81 mmol/L. Skeletal survey showed no changes in 24 patients (42%), hyperparathyroid cystic changes of bones in seven, osteoporosis as the predominant features in seven, mixed picture of ROD in 12, subperiosteal resorption of the metacarpals in two, osteosclerosis (Rugger Jersey Spine) in two and osteomalacia in two patients. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). All patients had low BMD (both LS and FN). Bone biopsy (BBX) revealed mixed picture in 30 cases, predominantly secondary hyperparathyroid changes in 10, mild hyperparathyroid changes in five, predominant osteoporosis in three, osteomalacia in four, aplastic (adynamic) bone in four, and aluminum deposition in one. All of the patients who showed evidence of bone involvement on BBX had abnormal BMD suggesting that BMD is a good non-invasive screening test for ROD but indiscriminative for the type of bone disease. BBX still remains the diagnostic tool to differentiate and classify different types of bone disease.
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PMID:Spectrum of renal osteodystrophy in dialysis patients at a tertiary hospital, riyadh, saudi arabia. 1840 87

Hypophosphatasia (HPP) is the inborn error of metabolism that features low serum alkaline phosphatase (ALP) activity caused by loss-of-function mutation(s) within the gene for the tissue nonspecific isoenzyme of ALP (TNSALP). In HPP, extracellular accumulation of inorganic pyrophosphate (PPi), a TNSALP substrate and inhibitor of mineralization, leads frequently to premature tooth loss and often to rickets or osteomalacia. In affected adults, the excess PPi sometimes also causes calcium pyrophosphate dihydrate (CPPD) deposition, PPi arthropathy, or pseudogout, or seemingly paradoxical deposition of hydroxyapatite crystals in ligaments or around joints when the condition is called calcific periarthritis (CP). We report three middle-aged sisters with CP as the only clinical manifestation of HPP. Each presented during early adult life with recurrent episodes of pain principally around the shoulders, elbows, wrists, hips, or Achilles tendon. Otherwise, they were in good health, including no history of unusual dental disease, fractures, or pseudofractures. Calcific deposits were identified in symptomatic areas principally by ultrasonographic assessment but also confirmed radiographically. All three sisters had low serum levels of total and bone-specific ALP, hyperphosphatemia, and increased serum concentrations of the TNSALP substrate pyridoxal 5'-phosphate together characteristic of HPP. Mutation analysis revealed that each carried a single unique 18-bp duplication within TNSALP (c.188_205dup18, p.Gly63_Thr68dup) as did two of their healthy sons and their mother, who was without signs of CPPD deposition or CP but had knee osteoarthritis. We find that CP can be the only complication of HPP in adults. Thus, multiple juxta-articular deposits of hydroxyapatite causing CP may be a useful sign of HPP, especially when the CP is familial.
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PMID:Calcific periarthritis as the only clinical manifestation of hypophosphatasia in middle-aged sisters. 2412 10