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Results for “Calcium Pyrophosphate”

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PubMed1999

Crystal-induced inflammation and cartilage degradation.

In the past year, there have been advances in our understanding of the induction of cartilage damage by calcium-containing crystals. Mechanisms of deposition and the biologic effects of crystals have been further characterized, as has the interaction between crystals and leukocytes. Studies of the clinical diagnosis of crystal deposition diseases suggest that accuracy with microscopy needs to be enhanced. Normal values for serum NTPPPHase have been established and optimal diagnostic imaging strategies for calcium pyrophosphate deposition disease have been suggested. There are still no available drugs to inhibit deposition or effect reabsorption of calcium-containing crystals.

Calcinosis↗

PubMedDate not supplied

[Study of crystals in synovial exudations with simultaneous determination of adequate enzymes].

The paper presents the results of study of 28 synovial exudations in which the uricase method was used for uric acid determination with simultaneous pyrophosphatase and cathepsin C and D activity determination. The presence of crystals in these exudations was investigated as well. From the study follows that a higher uric acid level and higher pyrophosphatase activity coincide with the finding of urate and pyrophosphate crystals. The reported method of examination applies also to other identifications of microcrystals or crystalline split of urates or calcium pyrophosphate dihydrate in the exudation. The activity of cathepsin D permits to conclude on potential participation of peptides and/or polypeptides in the formation of crystals in the exudation.

Adolescent↗

PubMed1982

Pyrophosphate arthropathy: a clinical and radiological study of 105 cases.

105 consecutive patients who presented to a rheumatologist because of joint disease and who also had evidence of deposition of calcium pyrophosphate dihydrate (CPD) were studied clinically and radiologically. There were 76 women (mean age 73) and 29 men (mean age 62). Of only 18 patients below the age of 60 at presentation 12 were men. The majority of the younger male group suffered from acute attacks of synovitis, and had no clinical or radiological evidence of joint damage. In contrast the older female group had widespread destructive changes. Associated joint disease included generalised osteoarthritis (45), rheumatoid arthritis (8), joint hypermobility (13), previous knee surgery (8), and gout 92). Sixteen patients had received long-term steroid therapy. Severe destructive joint changes were seen in 16 patients. The radiological features in those with rheumatoid arthritis by ARA criteria were atypical. The relationship between CPD deposition and arthritis is discussed in the light of these findings.

Acute Disease↗

PubMed2000

Calcium and disease: molecular determinants of calcium crystal deposition diseases.

Deposition of basic calcium phosphate (hydroxyapatite, octacalcium phosphate and tricalcium phosphate) (BCP) and crystalline calcium pyrophosphate dihydrate (CPPD) is associated with a variety of aging-related pathologies, including osteoarthritis, cartilage degeneration and pseudogout. These diseases of calcium deposition serve as some of the best-studied examples of how calcium-regulated changes in gene expression can directly lead to pathogenic consequences. Tissue damage can result when crystals stimulate cells to release matrix-degrading molecules or secrete cytokines that stimulate the release of matrix-degrading molecules. Exposure of cultured cells to crystals induces expression of cellular proto-oncogenes such as c-fos, c-myc and c-jun, by a calcium-dependent mechanism, and this response can be blocked by a potential therapeutic compound, phosphocitrate. Activation of the c-fos and c-jun genes is directly involved in expression of metalloproteinases such as collagenase and stromelysin, suggesting that crystal-mediated activation of these genes is directly involved in pathogenesis. In this review recent advances in the molecular mechanisms responsible for crystal-mediated cell activation are discussed.

Animals↗

PubMed1988

Evidence that ecto-nucleoside-triphosphate pyrophosphatase serves in the generation of extracellular inorganic pyrophosphate in human bone and articular cartilage.

Extracellular inorganic pyrophosphate (PPi) is important in the regulation of mineralisation of bone, and in the pathogenesis of chondrocalcinosis, an arthritic disease in which calcium pyrophosphate dihydrate crystals form in articular cartilage. Nucleoside-triphosphate pyrophosphatase, which catalyses the formation of PPi, was previously observed at the surface of human articular chondrocytes in culture. A similar enzyme has been identified in osteoblast-like human bone cells in culture, and is active towards purine and pyrimidine nucleoside triphosphates. The enzyme has high affinity for ATP and is located on the cell surface, and thus could serve in the generation of extracellular PPi. Moreover, no other mechanism for the catabolism of small amounts of exogenous ATP is present in human bone cells. Further evidence for ecto-nucleoside-triphosphate pyrophosphatase serving in the generation of extracellular PPi in articular cartilage and bone was obtained by studying the ability of alternative substrates (which do not yield PPi) to inhibit generation of PPi from ATP. In both articular chondrocytes and bone cells, the enzyme exhibited an apparent preference for ATP over dinucleotide and phosphodiester substrates. Some potential inhibitors of the enzyme activity were also studied in both cell types. ADP moderately inhibited the activity but two bisphosphonate drugs were only slightly inhibitory.

Bone Matrix↗

PubMed1985

Inhibition of hydroxyapatite formation in collagen gels by chondroitin sulphate.

Crystal growth in native collagen gels has been used to determine the role of extracellular matrix macromolecules in biological calcification phenomena. In this system, type I collagen gels containing sodium phosphate and buffered at pH 7.4 are overlayed with a solution containing CaCl2. Crystals form in the collagen gel adjacent to the gel-solution interface. Conditions were determined which permit the growth of crystals of hydroxyapatite [Ca10(PO4)6(OH)2]. At a Ca/P molar ratio of 2:1, the minimum concentrations of calcium and phosphate necessary for precipitation of hydroxyapatite are 10 mM and 5 mM, respectively. Under these conditions, precipitation is initiated at 18-24h, and is maximal between 24h and 6 days. Addition of high concentrations of chondroitin 4-sulphate inhibits the formation of hydroxyapatite in collagen gels; initiation of precipitation is delayed, and the final (equilibrium) amount of precipitation is decreased. Inhibition of hydroxyapatite formation requires concentrations of chondroitin sulphate higher than those required to inhibit calcium pyrophosphate crystal formation.

Calcium↗

PubMed2006

Investigation of the role of ENPP1 and TNAP genes in chondrocalcinosis.

OBJECTIVES: Extracellular inorganic pyrophosphate (ePPi) inhibits certain forms of pathological mineralization while promoting others. Three molecules involved in ePPi regulation are important candidates for the development of calcium pyrophosphate dihydrate chondrocalcinosis (CPPD CC). These include ANKH, ectonucleotide pyrophosphatase (ENPP1) and TNAP. We have previously showed that genetic variation in ANKH is a cause of autosomal dominant familial CC and also some sporadic cases of CPPD CC. We now investigate the possible role of ENPP1 and TNAP in CPPD CC. METHODS: Exons, untranslated regions (UTR) and exon-intron boundaries of ENPP1 and TNAP were sequenced using ABI Big Dye chemistry on automated sequencers. Sixteen variants were identified (3 in ENPP1 and 13 in TNAP) and were subsequently genotyped in 128 sporadic Caucasian CPPD CC patients and 600 healthy controls using a combination of polymerase chain reaction/restriction fragment-length polymorphism analysis or using Taqman. Allele and genotype frequencies were compared between cases and controls using the chi(2) test. Linkage disequilibrium, haplotype and the single nucleotide polymorphism-specific analyses were also performed. This study had 80% power to detect an odds ratio of 2.2 or more at these loci. RESULTS: No difference was observed in the allele or genotype frequencies between patients and controls at either ENPP1 or TNAP. CONCLUSIONS: Polymorphisms of ENPP1 and TNAP are not major determinants of susceptibility to CC in the population studied. Further studies of the aetiology of sporadic CPPD CC are required to determine its causes.

Aged↗

PubMed2002

Animal models of pathologic calcification.

Recent progress in genetics and mouse genomics enables researchers to unveil the molecular basis for mouse phenotypes that express pathologic calcification in soft tissue and/or articular tissues. A newly identified multipass transmembrane protein, ANK, appears to function as an inorganic pyrophosphate (PPi) transporter or regulator of PPi transport. Abnormal extracellular PPi (ePPi) metabolism has been implicated in abnormal calcification, decreased concentrations predisposing to basic calcium phosphate (BCP) deposition, and increased concentrations promoting calcium pyrophosphate dihydrate (CPPD) crystal deposition in articular tissues. The chromosomal location of human ANK overlaps the locus identified in several kindreds affected with familial chondrocalcinosis. Deficient generation of ePPi by the ectoenzyme nucleoside triphosphate pyrophosphohydrolase also results in excessive ossification and ectopic deposition of BCP crystals in tiptoe-walking mice and PC-1 null mice. Recent studies reinforce the important regulatory role of ePPi in pathologic and physiologic calcification.

Animals↗

PubMed1993

Clinical utility of the alizarin red S stain on permanent preparations to detect calcium-containing compounds in synovial fluid.

The alizarin red S stain for permanent cytologic preparations is a valuable test that is complementary to compensated polarized light microscopic examination to detect calcium crystals. Alizarin red S has the greatest sensitivity for detection of calcium pyrophosphate crystals because crystals are stained regardless of how weakly or strongly birefringent they may be. Alizarin red S stain does not distinguish between amorphous types of calcium compounds; therefore, the different types of calcium compounds can be distinguished only when typical crystal morphologic features are present. Diagnostic importance can be attached to intracellular material that is stainable. In contrast, the diagnostic value of stainable, amorphous, extracellular material is unreliable because it is difficult to distinguish this extracellular material from contaminants frequently found in clinical specimens. Alizarin red S does not stain monosodium urate or corticosteroid crystals. Air-dried cytospin smears are helpful because they may frequently demonstrate more crystals than the wet-mount preparation. Furthermore, special stains can be performed subsequently on air-dried cytospin smears if necessary.

Anthraquinones↗

PubMed1980

Bone kinetics of calcium-45 and pyrophosphate labeled with technetium-96: an autoradiographic evaluation.

The uptake of calcium-45 and of pyrophosphate labeled with the long-lived technetium-96 isotope were compared by means of liquid-emulsion microautoradiograms of the epiphyseal plates of 10-week-old rabbits, at 30 min, and 3 and 48 hr after i.v. administration. For both tracers, thin sections confirm the significant role of the blood supply, especially shortly after injection. However, other more specific mechanisms lead to a mixing of the calcium in the mineral mass and to a linear deposition of technetium facing the osteoid surfaces. These findings suggest that the tropism of tin-reduced technetium pyrophosphate is not governed by the mineral pool but rather by exchanges inside a still poorly calcified organic matrix.

Animals↗

PubMed1997

Calcium carbonate apatite deposition in the cervical spine with associated vertebral destruction. Case report.

This 52-year-old woman developed crystal deposition disease involving the cervical vertebrae. She presented with symptomatic spinal cord compression secondary to extensive calcified lesions in the posterior elements of the cervical spine. Surgical decompression with posterior fusion was performed. Histological examination showed hardened deposits of calcium carbonate involving the soft tissue, and dissolution of the vertebral bone trabeculae. There was no inflammatory response to these deposits. One year postoperatively the patient developed severe pulmonary disease associated with the collagen-vascular disorder, scleroderma (calcinosis, Raynaud's phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia [CREST] syndrome). Calcium carbonate deposition disease represents an unusual clinical entity that is possibly associated with scleroderma or other collagen-vascular diseases, and it is distinct from ligamentum flavum calcification, calcium pyrophosphate deposition disease, and hydroxyapatite deposition disease.

Apatites↗

PubMed1998

A quantitative study of the sintering and mechanical properties of hydroxyapatite/phosphate glass composites.

Previous work has shown that small additions of a phosphate glass (CaO-P2O5) can significantly enhance the sinterability and strength of hydroxyapatite. However, there are no quantitative phase analyses available for these materials which would provide indicators of biocompatibility and resorbability. Similarly, there is little information available about the mechanical properties, especially with high glass additions. In this study, the effects of sintering hydroxyapatite with phosphate glass additions of 2.5, 5, 10, 25, and 50 wt.% are quantified. Each composition was sintered over a range of temperatures, and quantitative phase analysis was carried out using XRD. In addition, the microstructures were studied using RLOM and SEM, and mechanical properties (Vickers hardness, KIC, and MOR) measured. These results may be used to indicate which compositions and processing conditions may provide materials suitable for use in hard tissue replacement. Composites containing up to 10 wt.% glass additions formed dense HA/TCP composite materials possessing flexural strength and fracture toughness values up to 200% those of pure HA. The HA/TCP ratio was strongly dependent on the percentage glass addition. Higher glass additions resulted in composites containing beta-TCP together with large amounts of alpha- or beta-calcium pyrophosphate, and having similar mechanical strengths to pure HA.

Biocompatible Materials↗

PubMed2006

Effect of whitening dentifrices on the superficial roughness of esthetic restorative materials.

PURPOSE: The purpose of this study was to investigate the surface roughness (Ra) of different esthetic restorative materials following simulated toothbrushing using different whitening dentifrices. MATERIALS AND METHODS: Cylinders of Esthet-X (Dentsply Caulk, Milford, DE, USA), Durafil VS (Heraeus Kulzer, Wehrheim, Germany), and Vitremer (3M ESPE, St. Paul, MN, USA) were made using molds (4 mm in diameter for 2 mm in height). The superficial roughness was evaluated using a profilometer (Ra) with a cutoff length of 0.25 mm and a speed of 0.1 mm/s. The specimens (N=13) were submitted to 7,500 brushing cycles using five different toothpastes: (1) Crest Regular (control; Procter & Gamble): silica abrasive (C); (2) Crest Extra Whitening (Procter & Gamble, Cincinnati, OH, USA): bicarbonate+calcium pyrophosphate (CE); (3) Dental Care A & H (Arm & Hammer, Camilla, GA, USA): bicarbonate (DC); (4) Rembrandt Plus Whitening (Oral B Laboratories, Belmont, CA, USA): carbamide peroxide+alumina/silica (RP); and (5) experimental: hydrogen peroxide+calcium carbonate (EX). RESULTS: The data were analyzed by analysis of variance and Tukey's test (alpha=.05) for each restorative material, and the results [difference between final and initial roughness: Ra(F)-Ra(I) in microm] were as follows: Esthet-X: EX=0.15+0.07a; RP=0.29+0.16a; CE=0.96+0.33b; C=1.03+0.29b; DC=1.48+0.37b; Durafil VS: RP=0.09+0.07a; EX=0.55+0.23abc; C=0.96+0.26bc; CE=1.03+0.33cd; DC=1.09+0.37d; and Vitremer: EX=0.10+0.08a; RP=0.26+0.19a; CE=0.94+0.27b; DC=1.13+0.46bc; C=1.50+0.32c (different letters mean differences among groups). CONCLUSION: It was verified that the dentifrices containing carbamide or hydrogen peroxide along with alumina+silica and calcium carbonate, respectively (groups 4 and 5), produced minor changes in Ra when compared with the control group and with those dentifrices containing bicarbonate (groups 2 and 3). CLINICAL significance The results of this study indicate that whitening dentifrices evaluated containing silica or calcium carbonate were less abrasive when used on the resin-based esthetic restorative materials than those that contain sodium bicarbonate.

Aluminum Oxide↗

PubMed1976

The arthropathy of hemochromatosis.

Five cases of hemochromatosis arthropathy are presented and the distinctive radiological features of the disease are described. Although the condition is typically degenerative, showing subchondral cyst formation, sclerosis, and thinning of cartilage, its distribution is characteristic. Selective degenerative changes of the second and third metacarpophalangeal joints are striking, particularly in the hands, while abnormalities in the intercarpal joints are variable and the interphalangeal joints are spared. Chondrocalcinosis involving both fibrous and hyaline cartilage is frequently seen as well, particularly in the large joints. The calcification is due to deposition of calcium pyrophosphate crystals, perhaps resulting from iron inhibition of pyrophosphatase.

Adult↗

PubMed1975

Pyrophosphate arthropathy.

A scanning electron microscopic study of six cases of pyrophosphate arthropathy has been conducted. In the majority of cases the crystals were rectangular. In some cases giant crystals were present. In one case, the crystals were pyramidal. It is concluded that many geometrically different forms of calcium pyrophosphate crystal exist and that the scanning electron microscope is a useful tool in the differentiation of pyrophosphate arthropathy from other forms of crystal synovitis.

Cartilage, Articular↗

PubMed2005

Consequences and management of hyperphosphatemia in patients with renal insufficiency.

Consequences and management of hyperphosphatemia in patients with renal insufficiency. Progressive renal insufficiency leads to hyperphosphatemia, hypocalcemia, and secondary hyperparathyroidism. Bone demineralization in secondary hyperparathyroidism may induce fractures, while joint and subcutaneous precipitations of calcium pyrophosphate limit mobility, and may cause crippling. Strategies to preempt bone and joint destruction in chronic kidney disease and end-stage renal disease have focused on limiting dietary phosphorus, intra-gut binding of ingested phosphorous, enhancing calcium absorption, and limiting parathyroid hormone secretion. Deciding which regimen is most effective to meet these treatment objectives challenges nephrologists; they often uncover conflicting evidence about which abnormal metabolite should be the prime treatment objective. Especially vexing is the question of whether hypercalcemia is a cardiotoxic consequence of calcium-based phosphate binders.

Acetates↗

PubMed1977

Arthritis associated with apatite crystals.

Needle-shaped crystals of 75 to 250 A diameter have been identified by transmission electron microscopy in clumps within synovial fluid mononuclear cell vacuoles in a variety of joint diseases. These crystals, similar to those previously associated with calcific periarthritis, were seen in acute undiagnosed arthritis and in exacerbations of osteoarthritis where they may be inducing a synovitis similar to that seen with urate and pyrophosphate crystals in gout and pseudogout. By light microscopy purple staining cytoplasmic inclusions or extracellular globules can suggest the presence of clumps of these crystals. Apatite clumps can also occasionally appear as small birefringent chunks or rods and thus might mimic urate or calcium pyrophosphate. Ultrastructural appearance, electron probe analysis, and X-ray diffraction pattern were those of apatite. Experimental injection of hydroxyapatite crystals into dog knee joints produces inflammation supporting the potential role for these crystals in joint disease.

Acute Disease↗

PubMed1980

The arthropathy of maintenance intermittent peritoneal dialysis.

Among 61 patients undergoing maintenance peritoneal dialysis for an average of 20 months, 13 (21%) had a history of attacks of acute arthritis and 19 (31%) were found to have tender and often swollen joints. Deposits of calcium pyrophosphate dihydrate crystals in articular cartilage were identified in four patients and inflammation probably induced by hydroxyapatite crystals was noted in one. Periarticular calcification was observed in 12 patients and subperiosteal resorption of the phalanges in 20. The average calcium X phosphorus product was significantly higher (P < 0.025) in patients with a history of attacks of acute arthritis or with inflamed joints (58 +/- 12) than in those without (50 +/- 12). In the 19 patients whose treatment was changed to continuous ambulatory peritoneal dialysis there was a significant decrease (P < 0.025) in the calcium X phosphorus product but not in the proportion of patients with attacks of acute arthritis or with inflamed joints. The results indicate that articular complications are frequent among patients undergoing maintenance peritoneal dialysis and may be more common than with long-term hemodialysis.

Acute Disease↗