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PubMed1992

In-111 labeled leukocyte imaging in a case of pseudogout.

In-111 labeled leukocyte scintigraphy was performed on a 90-year-old woman who had a fever and left lower extremity pain for 3 days. Leukocyte images demonstrated abnormal activity in the left knee and ankle. Aspiration of the left knee joint yielded cloudy yellow fluid with a leukocyte count of 30,000 per mm3 (75% polymorphonuclear leukocytes, 1% lymphocytes, and 24% monocytes). Cultures of the aspirate were reported as no growth. Microscopic examination of the aspirate revealed the presence of rod-shaped crystals of calcium pyrophosphate dihydrate, confirming the diagnosis of calcium pyrophosphate deposition disease, also known as pseudogout. The acute arthritis of pseudogout stimulates an intense leukocyte response; therefore, labeled leukocyte images performed on patients suspected of having this condition must be interpreted cautiously because scintigraphically it may not be possible to distinguish pseudogout from septic arthritis.

Aged↗
PubMed1993

Crystal-induced neutrophil activation. III. Inflammatory microcrystals induce a distinct pattern of tyrosine phosphorylation in human neutrophils.

The activation of human neutrophils by monosodium urate and calcium pyrophosphate dihydrate crystals is believed to play a critical role in the pathogenesis of arthritides such as acute gout and pseudogout, respectively. In this study, we investigated the potential involvement of tyrosine phosphorylation in microcrystal-mediated activation of human neutrophils. Immunoblot analysis with antiphosphotyrosine antibodies demonstrated that triclinic monosodium urate and calcium pyrophosphate dihydrate crystals stimulated a time- and concentration-dependent tyrosine phosphorylation of at least five proteins (pp130, 118, 80, 70, and 60). While phosphoprotein (pp) 118 and pp70 were the major phosphorylated substrates, pp70 was the dominant one in reactivity with antiphosphotyrosine antibodies. When the temporal patterns, as well as the levels of tyrosine phosphorylation for both types of crystals were compared, monosodium urate crystals were found to be more potent activators than calcium pyrophosphate dihydrate crystals. The tyrosine phosphorylation patterns induced by microcrystals differed from those stimulated by other soluble (FMLP, C5a, or leukotriene B4) or particulate (unopsonized latex beads or zymosan) agonists which stimulated preferentially the tyrosine phosphorylation of pp118. The ratio of the intensities of pp118 and pp70 were specific of the stimulation with microcrystals when compared to those observed with the other soluble or particulate agonists. Colchicine, a drug used specifically in the treatment of gout and pseudogout, inhibited microcrystal-induced tyrosine phosphorylation, while beta- and gamma-lumicolchicine were without effect. On the other hand, colchicine failed to inhibit FMLP-induced tyrosine phosphorylation. Furthermore, while colchicine inhibited the activation of the NADPH oxidase by microcrystals, it, on the other hand, enhanced the production of superoxide anions by FMLP. Taken together, these results (a) demonstrate that tyrosine phosphorylation is involved in the mechanism of activation of human neutrophils induced by microcrystals; and (b) suggest, on the basis of the characteristics of the observed patterns of tyrosine phosphorylation, that this response may be specific to the microcrystals and relevant to their phlogistic properties.

Adult↗
PubMed1989

Calcium, lanthanum, pyrophosphate, and hydroxyapatite: a comparative study in fibroblast mitogenicity.

Calcium-containing crystals and elevated levels of calcium chloride (CaCl2) and lanthanum chloride (LaCl3) have been previously reported to enhance the proliferative activity of cultured fibroblasts. We have investigated the relative mitogenicity of these agents, whether they function via precipitation on the cell surface and whether they interact with one another. Confluent cultures of newborn foreskin fibroblasts provided with fresh medium containing 10% fetal bovine serum (FBS) in the presence of hydroxyapatite (HA), pyrophosphate (PPi), LaCl3 (La), or additional CaCl2 (Ca) were all stimulated more than control cultures provided with fresh medium and 10% FBS alone as assessed by cell counts 5 days later. Increases in cell yield above the original confluent cell density were 316% for La, 271% for Ca, 189% for HA, 131% for PPi, and 45% for controls. Addition of fresh medium containing 10% FBS and epidermal growth factor or fresh medium containing 20% FBS as additional points of reference yielded increases of 204 and 107%, respectively, over original confluent density. Stimulation induced by La or Ca was significantly greater (P less than 0.001) than the stimulation induced by each of the other treatments. The same treatments added to confluent cultures without a change of medium also renewed mitotic activity, with La and Ca again the most mitogenic and approximately doubling the pretreatment cell yields. Cultures incubated in an inverted position to avoid cell contact with precipitates in the medium were also stimulated by La and Ca, but not by HA and PPi. When added to confluent cultures simultaneously supplemented with optimal additional Ca, La decreased Day 5 cell yields in a dose-dependent manner at low concentrations (0.03-0.2 mM) but increased cell yields over those obtained with 0.2 mM LaCl3 again in a dose-dependent manner at higher concentrations. Thus, while HA and PPi act via precipitation on the cell surface, the more mitogenic agents La and Ca function in solution and appear to stimulate cell division by different nonadditive mechanisms. These findings suggest multiple mechanisms of membrane participation in mitogen responsiveness and in density-dependent inhibition of growth.

Calcium Chloride↗
PubMed1996

Tumoral calcinosis in the upper cervical spine: a case report.

STUDY DESIGN: An elderly women with tumoral calcinosis between the C1 posterior arch and the C2 lamina is reported. OBJECTIVES: To describe a rare occurrence of tumoral calcinosis in the spine and discuss its pathomechanism. SUMMARY OF BACKGROUND DATA: Tumoral calcinosis is a rare condition occurring predominantly in the juxtaarticular regions of the extremities. Involvement of the spine has been reported in only one case in the lumbar spine. The calcium phosphate crystals that have been identified are those of hydroxyapatite. METHODS: The calcified material was removed, and its crystalline phase was analyzed. RESULTS: Neck pain was relieved by removal of the calcified material. Scanning electron microscopy and energy-dispersive x-ray microanalysis revealed that the material consisted of crystals of calcium pyrophosphate dihydrate. CONCLUSIONS: Tumoral calcinosis should be included among the clinical presentations of calcium pyrophosphate dihydrate crystal deposition disease.

Aged↗
PubMed1999

Crystal deposition and osteoarthritis.

Calcium-containing crystals are commonly found in osteoarthritic (OA) joints. Although most often found in advanced OA, some calcium pyrophosphate dihydrate and apatite can be present in early stages. These crystals could be factors in pathogenesis of OA and even more likely in the progression of disease. Calcium pyrophosphate dihydrate apatites and other calcium phosphates can be mitogenic, can stimulate the release of metalloproteases, and might have mechanical abrasive effects.

Aged↗
PubMed2006

Role of the progressive ankylosis gene in cartilage mineralization.

PURPOSE OF REVIEW: Among the myriad of players in the calcification of cartilage, ANK is a relatively new entrant. It is a multipass transmembrane protein that regulates the transport of inorganic pyrophosphate between the cell and the extracellular space. Mutations in ANK result in two distinct calcification disorders: craniometaphyseal dysplasia and familial calcium pyrophosphate dihydrate deposition disease. The purpose of this review is to highlight recent work on the role of ANK in physiological and pathological calcification of articular and growth plate cartilage. RECENT FINDINGS: New information on the function of ANK suggests that the protein is part of a constellation of critical components that interact to regulate the elaboration of inorganic pyrophosphate. In addition to ANK, these components include alkaline phosphatase, the ectoenzyme PC-1, and osteopontin. ANK expression is also regulated by a variety of growth factors and cytokines that may further affect the transport of inorganic pyrophosphate and may be particularly relevant to the increased levels of expression of ANK in cartilage from chondrocalcinosis and osteoarthritis patients. SUMMARY: Additional studies will be required to understand the contribution of ANK in shaping the fine balance of components necessary for crystal deposition in degenerating articular cartilage. Furthermore, the precise role of inherited mutations in ANK on the elaboration of inorganic pyrophosphate, and the ultimate deposition of either basic calcium phosphate or calcium pyrophosphate dihydrate crystals, remains unclear.

Calcinosis↗
PubMed2004

Pseudogout of the transverse atlantal ligament: an unusual cause of cervical myelopathy.

BACKGROUND: Calcium pyrophosphate dihydrate deposition in the cervical spine is infrequently symptomatic. This is especially true at the craniocervical junction and upper cervical spine. CASE REPORT: A 70-year-old previously healthy woman presented with a progressive cervical myelopathy of four months duration. RESULTS: Examination revealed sensorimotor findings consistent with an upper cervical myelopathy. Radiological studies (plain radiographs, computed tomography, and magnetic resonance imaging) revealed C1-2 instability, and a well-defined extradural 3 cm x 1 cm retro-odontoid mass causing spinal cord compression. Transoral resection of the mass was performed followed by posterior C1-2 stabilization. Histological examination of the mass confirmed calcium pyrophosphate dihydrate deposition. Follow-up examination showed marked clinical and radiological improvement. CONCLUSION: Although uncommon, calcium pyrophosphate dihydrate deposition disease should be considered in the differential diagnosis of extradural mass lesions in the region of the odontoid.

Aged↗
PubMed1981

Release of pyrophosphate by normal mammalian articular hyaline and fibrocartilage in organ culture.

Calcium pyrophosphate dihydrate crystals are found most frequently in fibrocartilaginous tissue and to a lesser extent in hyaline articular cartilage. Previous investigators found that pyrophosphate (PPi) was released into the medium by immature rabbit hyaline cartilage and osteoarthritic human cartilage in organ culture but not by normal human or mature rabbit cartilage. By employing a sensitive fluorometric assay for PPi and correcting for hydrolysis of PPi during the incubations, we detected PPi release by all normal mammalian cartilage studied. PPi release per mg wet weight of lapine and canine cartilage was paralleled by uronic acid production. Meniscal fibrocartilage, the most common site of calcium pyrophosphate deposits, also elaborate PPi.

Animals↗
PubMed2001

Familial calcium crystal diseases: what have we learned?

The spectrum of heterotopic calcification or ossification is expanding because of the reports of several kindreds with calcium pyrophosphate deposition disease, apatite deposition disease, and others with less common syndromes associated with extracellular matrix calcification, such as fibrodysplasia ossificans progressiva and related syndromes. Genomic DNA studies in both humans and mice provide a shortcut to understanding the genetic basis of promotion and prevention of ECM calcification. Mutation in the COL2A1 gene has been identified in one family with spondyloepiphyseal dysplasia and calcium pyrophosphate and apatite crystalline deposits. In another kindred with precocious osteoarthritis without spondyloepiphyseal dysplasia, the phenotype was linked to markers of chromosome 8. In four other kindreds, the phenotypes were linked to an area of chromosome 5p. Two genes located in this region, which are expressed in articular cartilage, are being investigated as possible calcium pyrophosphate deposition disease genes. The results of linkage studies in three kindreds with articular/periarticular ADD with the COL2A1 gene were noninformative. Two different mouse mutations, the ank/ank and the ttw/ttw mice, are associated with intra-articular and ligament apatite deposits caused by a decrease in extracellular pyrophosphate concentrations, mimicking human arthritis caused by apatite deposition disease. Mutations in the matrix GLA protein, both in mice and in humans, are also associated with vascular and articular calcification. These mouse mutations provide cutting-edge information in the investigation of the mechanisms of apatite deposition in humans.

Calcinosis↗
PubMed1999

Transduction mechanisms of porcine chondrocyte inorganic pyrophosphate elaboration.

OBJECTIVE: To investigate cellular signaling mechanisms that influence chondrocyte production of inorganic pyrophosphate (PPi), which promotes calcium pyrophosphate dihydrate (CPPD) crystal deposition. METHODS: Articular chondrocyte and cartilage cultures were stimulated with protein kinase C (PKC) activator and adenyl cyclase activator. Generation of extracellular PPi was measured. RESULTS: Adenyl cyclase activation resulted in diminished pyrophosphate generation. PKC activation stimulated pyrophosphate elaboration. CONCLUSION: Two signaling pathways, cAMP and PKC, modulate generation of extracellular pyrophosphate by cartilage and chondrocytes. They are novel targets for potentially diminishing extracellular pyrophosphate elaboration that leads to CPPD crystal deposition.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2005

Fractal analysis of acceleration signals from patients with CPPD, rheumatoid arthritis, and spondyloarthroparthy of the finger joint.

Arthritis is one of the leading causes of disability and affects a major segment of the population. Consequently, accurate diagnosis of arthritis is important. Arthritis due to calcium pyrophosphate deposition disease (CPPD), rheumatoid arthritis, and spondyloarthropathy, induce complex changes in the cartilage and the articular surface. The fractal dimension provides a measure of the complexity of a signal. Recently, we have developed non-invasive acceleration measurements to characterize the arthritic patients. The question remains if the fractal dimension of the acceleration signal is different for different arthritis conditions. The purpose of this study was to distinguish between different types of arthritis of the finger joint using the fractal dimension of the acceleration signal obtained from the finger joint of the arthritic patients. Acceleration signals were obtained from the finger joint of arthritis patients with rheumatoid arthritis, spondyloarthropathy, and calcium pyrophosphate deposition disease of the finger joint. ANOVA results showed that there were significant differences between the fractal dimension of acceleration signals from patients having calcium pyrophosphate deposition disease and rheumatoid arthritis and spondyloarthropathy. Fractal dimension of acceleration signals, in concert with other clinical symptoms, can be used to classify different types of arthritis.

Arthritis, Rheumatoid↗
PubMed1984

Study of the evolution of acute phase reactants and of thromboxane and prostacyclin during calcium pyrophosphate-induced pleurisy in the rat.

By using a clearly defined model of acute inflammation in rats, CaPP-induced pleurisy, we compared the evolution of four APR levels (Hp, HpX, alpha 2M, SAP) at a local and peripheral site. At the same time we studied thromboxane and prostacyclin concentrations in pleural exudate. The levels of APR have shown a progressive increase up to 24 h. For alpha 2M, Hp, HpX the increase in serum concentration was more rapid than in exudate, whereas the evolution of SAP level was parallel in the intra and extra-vascular compartments. On the other hand the levels of albumin and transferrin which are not APR remained constant in serum and also in exudate from 6 h to 24 h. Thromboxane and prostacyclin levels reached a peak during the first two hours of the inflammatory reaction followed by a rapid decreased. These prostanoids may be considered as early and transient mediators of acute inflammation, whereas the acute phase proteins studied have a more prolonged role in the inflammatory reaction.

Acute-Phase Proteins↗
PubMed2005

Inflammation and tissue damage in crystal deposition diseases.

PURPOSE OF REVIEW: The crystal-induced arthropathies are characterized by self-limiting episodes of acute inflammation and chronic tissue damage. This review summarizes recent advances in the understanding of the cellular responses to monosodium urate, calcium pyrophosphate dihydrate and basic calcium phosphate crystals. RECENT FINDINGS: Factors such as the myeloid related proteins, endothelin-1 and the complement membrane attack complex have been recently identified as mediators of acute crystal-induced inflammation. In addition, signalling pathways involved in both acute inflammation and tissue damage in crystal arthropathies have been further clarified. The potential of macrophage-derived transforming growth factor beta1 to play a key role in the resolution phase of acute gout has also been demonstrated. SUMMARY: Recent work has provided new insights into the regulation of both acute and chronic articular responses to inflammatory microcrystals. Further analysis of these responses may identify potential therapeutic targets for management of the crystal-induced arthropathies.

Calcium Phosphates↗
PubMed1997

Carpal tunnel syndrome induced by two types of calcium deposition.

Two rare cases of carpal tunnel syndrome caused by calcification in the carpal tunnel are reported. One case involved a tumorous calcification consisting of basic calcium phosphate, and the other involved a diffuse calcification consisting of a mixture of calcium pyrophosphate dihydrate and basic calcium phosphate. These cases suggest that the shape of carpal tunnel calcifications is influenced by the nature of calcifying substance itself, i.e., whether it is heterogenous or homogenous.

Aged↗
PubMedDate not supplied

[Synovial fluid crystal identification by electron microscopy].

BACKGROUND: In clinical practice crystal identification in synovial fluid is made by polarized light microscopy and with some specific stainings. Nevertheless, sometimes we are unable to identify crystals by these means, either because they are too small or because they are widespread on the fluid. AIMS: To compare the identification of crystals in synovial fluid from patients with non-infectious monoarthritis but no history of local trauma or articular disease, using polarized light and electronic microscopy. METHODS: We analized synovial fluid samples from patients with non-infectious monoarthritis and no history of local trauma or articular disease. First we used a polarized light microscope and alizarin red staining. Later we used conventional transmission electron microscopy and energy dispersive spectroscopy, in order to identify and characterize crystals. RESULTS: Fourty-five samples from 23 synovial fluids were analyzed. Under polarized light microscopy we identified crystals on 11 samples: 3 with calcium pyrophosphate crystals, 6 with calcium basic phosphate crystals and 2 with sodium monourate crystals. On the remaining 12 samples we were unable to identify crystals. Samples were then analyzed by conventional transmission electron microscopy and energy dispersive spectroscopy confirming the presence of the previously identified crystals. On the remainig 12 samples we were able to identify calcium basic phosphate crystals. DISCUSSION: Microcrystals seem to be an universal finding in synovial fluid of patients with osteoarthritis. The prevention of their deposition in joints might contribute to stop joint damage in this disease.

Arthritis↗
PubMed1985

Pseudogout of the wrist presenting as acute median nerve compression.

Two cases are reported of acute median nerve compression due to calcium pyrophosphate deposition in the wrist, masquerading as a septic condition. There have been recent reports in the literature of the effects of calcium pyrophosphate in joints of the upper limb (Resnick 1983 and Hensley, 1983) These conditions are uncommon and the presentation and initial symptomatology of our case led in the first patient to misdiagnosis and an unnecessary operation, which was avoided in the second case.

Adult↗
PubMed1993

Four calcium phosphate ceramics as bone substitutes for non-weight-bearing.

Calcium phosphate ceramics, beta-calcium pyrophosphate (Ca2P2O7), beta-tricalcium phosphate (Ca3(PO4)2), hydroxyapatite (Ca10(PO4)6(OH)2) and tetracalcium phosphate (Ca4(PO4)2O), were prepared. The calcium:phosphorus ratios and microporosities were 1 (31.6%), 1.5 (1.6%), 1.66 (1%) and 2 (34.6%) respectively. Samples (15 mm x 10 mm x 2 mm), abraded with No. 2000 alumina powder, were implanted into the tibial metaphysis of mature male rabbits. Failure load, when an implant detached from the bone or the bone itself broke, was measured. At 10 wk after implantation, the failure loads in beta-calcium pyrophosphate, beta-tricalcium phosphate, hydroxyapatite and tetracalcium phosphate were 31.65 +/- 9.90 N, 72.81 +/- 19.01 N, 49.49 +/- 17.25 N and 43.22 +/- 14.99 N respectively. At 25 wk after implantation, the values were 47.04 +/- 14.90 N, 71.34 +/- 19.50 N, 69.09 +/- 16.17 N and 62.03 +/- 18.62 N respectively. Histologically, bone bonding behaviour of calcium phosphate ceramics did not vary with the calcium:phosphorus ratio, as observed by contact microradiogram, Giemsa surface staining and scanning electron micrograph-electron probe micro analysis. There was no intervening soft tissue at the interface of bone and ceramics. Hydroxyapatite or tricalcium phosphate are used as bone substitutes. However, their mechanical strength is insufficient for weight-bearing and they are used as bone filler. This study showed that the apparent insignificance of strict calcium:phosphorus ratio with respect to the biological results greatly simplifies processing of calcium phosphate ceramics for clinical application. In clinical application, calcium phosphate ceramics with different Ca:P can be used as bone fillers for bone defects or bone cavities under non-weight-bearing conditions.

Animals↗