Localization of 99mTc-labeled pyrophosphate and calcium in mycoardial infarcts after temporary coronary occlusion in dogs.
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Animals↗
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Results for “Calcium Pyrophosphate”
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Crystal-induced neutrophil activation. I. Initiation and modulation of calcium mobilization and superoxide production by microcrystals.
The effects of monosodium urate and calcium pyrophosphate dihydrate crystals on the levels of cytoplasmic free calcium and on the oxidative burst in normal human blood neutrophils were examined. The pattern of sensitivity to granulocyte-macrophage colony-stimulating factor, colchicine, cytochalasin B, pertussis toxin, diglyceride kinase, and protein kinase C inhibitors differentiated the mechanism(s) of neutrophil activation by the crystals from that involved in the responses to soluble chemotactic factors and indicated that individual crystals can use several activation pathways.
Alkaloids↗
Stimulation of inorganic pyrophosphate elaboration by cultured cartilage and chondrocytes.
Inorganic pyrophosphate elaboration by articular cartilage may favor calcium pyrophosphate dihydrate crystal deposition. Frequently crystal deposits form in persons affected with metabolic diseases. The cartilage organ culture system was used to model these metabolic conditions while measuring the influence on extracellular pyrophosphate elaboration. Alterations of ambient pH, thyroid stimulating hormone levels, and parathyroid hormone levels did not change pyrophosphate accumulation in the media. However, subphysiologic ambient calcium concentrations (25, 100, 500 microM) increased pyrophosphate accumulation about chondrocytes 3- to 10-fold. Low calcium also induced release of [14C]adenine-labeled nucleotides from chondrocytes, potential substrates for generation of extracellular pyrophosphate by ectoenzymes. Exposing cartilage to 10% fetal bovine serum also enhanced by 50% the egress of inorganic pyrophosphate from the tissue.
Animals↗
The role of calcium deposition in the ligamentum flavum causing a cauda equina syndrome and lumbar radiculopathy.
Our report concerns five patients who underwent lumbar decompressive surgery for cauda equina syndrome and radiculopathy secondary to degenerative stenosis associated with calcium deposition in the ligamentum flavum. The resected ligamentum flavum showed diffuse to massive calcium crystal deposition with a histologically marked degeneration in the elastic fibres. Energy dispensive radiographic microanalysis confirmed the crystal to be calcium pyrophosphate dihydrate in all patients, hydroxyapatite mixed in three and calcium orthophosphate mixed in one. The deposition appeared to be a change that is associated with the degenerative process in the ligament and, in some cases having marked deposition in a localised event, it causes or aggravates the neurological symptoms.
Aged↗
Acute pseudogout following parathyroidectomy.
Four patients developed acute arthritis following parathyroidectomy over a 3 year period in two general surgical practices. The diagnosis of pseudogout was made by clinical presentation, radiologic findings and demonstration of synovial fluid crystals exhibiting weakly positive birefringence. Rapid resolution of clinical arthritis followed joint aspiration and administration of anti-inflammatory agents in all four patients. Patients with hypercalcemia have a high incidence of calcium pyrophosphate dihydrate crystal deposition into joints. Rapid drops in serum calcium levels can cause shedding of these crystals into synovial fluid which may precipitate acute attacks of pseudogout. Because the relative hypocalcemia following parathyroidectomy provides a good stimulus for crystal shedding, it follows that hypercalcemic patients undergoing parathyroidectomy should experience a high incidence of acute pseudogout. Although this entity has been described before, its occurrence is not widely recognized in clinical practice. It is proposed that these four cases observed over a 3 year period indicate that pseudogout following parathyroidectomy occurs more commonly than previously recognized.
Calcium Pyrophosphate↗
Acute non-specific inflammation and modification of macrophage and lymphocyte functions.
The acute inflammatory response is a common phenomenon experienced by the physician in a wide variety of clinical situations. One of the major problems facing the investigator in this field of research who wishes to look at the cellular and humoral responses involved, is that in most of the animal models previously used, the inflammatory reaction has been provoked in subcutaneous tissues. Thus, a quantitative assessment of leucocyte emigration and mediator production in the inflamed area is technically difficult without resorting to complicated and artificial methods. Inflammation provoked in the pleural cavity provides a useful tool in the study of these problems since the collection of cells and analysis of humoral factors in exudates is easily accomplished. Among the irritants that may be used, we focused our interest on calcium pyrophosphate (CaPP) crystals, a non-diffusible, non-antigenic and endotoxin-free irritant, because their deposition is implicated in pseudogout and chondrocalcinosis in man (MacCarty, 1973). Calcium pyrophosphate-induced pleurisy is typified by an acute reaction, dominated by polymorphonuclear leucocytes, reaching its maximal intensity at about 5 h and disappearing within 48 h (Willoughby et al., 1975). It was found to be independent of the complement system. Examination of the known mediators of inflammation revealed no significant participation of either histamine or 5-hydroxytryptamine. There was an early rise in PGE2 followed by a greater rise in PGF2 alpha as the reaction diminished (Capasso et al., 1975). More recently, we have demonstrated the presence of a small quantity of thromboxane and a large quantity of prostacyclin during the first 2 hours of this inflammatory process. It was also shown that this type of acute inflammation was accompanied by the very rapid liberation of acute phase proteins both locally, in the exudate, and systemically in the serum (Tissot et al., 1983). Some of these events were also examined during the pleural reaction to other types of irritants (Capasso et al., 1975) and gave similar results (Tissot et al., 1983).
Animals↗
Calcium crystal deposition diseases: update on pathogenesis and manifestations.
Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate crystals are the most common types of pathologic calcium-containing crystals. Although these crystals long have been associated with a variety of rheumatic syndromes, recent evidence implicates BCP crystals in the pathogenesis of breast cancer and atherosclerosis. Although understanding of molecular mechanisms involved in generating these pathologic effects has been advanced significantly in recent years, they still are understood incompletely. Such advances are essential to the ongoing search for effective therapies for crystal-associated diseases.
Calcium Phosphates↗
Temporomandibular joint osteoarthritis and crystal deposition diseases: a study of crystals in synovial fluid lavages in osteoarthritic temporomandibular joints.
To study the presence of crystals in synovial fluid lavages of osteoarthritic temporomandibular joints (TMJs), in order to evaluate the possible role of these crystals in the osteoarthritic (OA) process, synovial fluid lavage samples of the upper joint compartment from 44 TMJs were obtained prior to arthroscopy. The OA group consisted of 32 TMJs. The control group consisted of 12 TMJs that had been diagnosed with other nonosteoarthritic conditions. The lavage samples were analysed as wet preparations, unstained and stained, with ordinary light, polarized light and compensated polarized light for the presence of crystals and white blood cells. One sample was prepared for subsequent electron microscopic (EM) examination. Synovial fluid lavage analysis of osteoarthritic TMJs did not show any monosodium urate monohydrate or calcium pyrophosphate dihydrate crystals. However, in three lavages, particles which possibly contained calcium were identified with alizarin red S staining. White blood cells were occasionally seen. Synovial fluid analysis of the lavages of the control TMJs did not reveal any crystals. EM examination of synovial fluid lavage from an osteoarthritic TMJ failed to clearly show crystal formation. Concurrence of TMJ crystal deposition and OA appears less prominent than in other synovial joints. We conclude that crystals probably do not play an important role in TMJ OA.
Adult↗
Modulation of chondrocyte production of extracellular inorganic pyrophosphate.
PURPOSE OF REVIEW: Extracellular inorganic pyrophosphate (ePPi) both inhibits and promotes different forms of pathologic mineralization. Basic calcium phosphate (BCP) deposition results from depressed levels of ePPi while excess levels of ePPi leads to calcium pyrophosphate dihydrate crystal deposition (CPPD) disease. These crystals are also often identified in patients with osteoarthritis, the most prevalent form of arthritis causing significant morbidity. RECENT STUDIES: The two primary hypotheses for generation of ePPi, export of inorganic pyrophosphate through the multipass transmembrane protein ANK and generation of ePPi by ectoenzyme activity, continue to be supported and better understood through animal models and study of families with CPPD deposition disease. SUMMARY: As the pathophysiology of crystal formation in both articular cartilage and synovial fluid is better understood, the opportunity for prevention and treatment of pathologic mineralization increases. In particular, a more complex understanding of the ank gene, ectoenzyme PC-1, and the transglutaminase enzyme family may eventually translate into therapeutic application for both BCP deposition and CPPD deposition disease.
Calcium Phosphates↗
A comparison of the effect of transforming growth factor beta 1 on pyrophosphate elaboration from various articular tissues.
OBJECTIVE: The purpose of this study was to determine the effect of transforming growth factor beta 1 (TGF beta 1) on inorganic pyrophosphate (PPi) elaboration from articular tissues to better understand the pathophysiology of calcium pyrophosphate dihydrate (CPPD) crystal deposition in the joint. METHODS: PPi was measured in the media of adult porcine articular tissue in organ culture and monolayer cultures. RESULTS: TGF beta 1 strongly stimulated PPi elaboration by porcine fibrocartilage and hyaline cartilage. It modestly increased PPi elaboration by ligament, and had no effect on PPi elaborated by synovium. Of all cell types tested in cell culture, only chondrocytes responded to TGF beta 1 by significantly increasing PPi elaboration. CONCLUSION: TGF beta 1 stimulates PPi elaboration from hyaline cartilage, fibrocartilage, and ligament, indicating that there is in situ CPPD crystal formation in these tissues. The ability of tissues to respond to TGF beta 1 by increasing PPi elaboration correlates with the prevalence of CPPD crystal deposition found clinically. The unique response of chondrocyte monolayers to TGF beta 1 reinforces the key role of the chondrocyte in PPi elaboration in the joint. These findings support an etiologic role for responsiveness to TGF beta 1 in CPPD disease.
Animals↗
Interactions of calcium and magnesium with the mitochondrial inorganic pyrophosphatase from Saccharomyces cerevisiae.
The activity of the mitochondrial inorganic pyrophosphatase from Saccharomyces cerevisiae was measured in the presence of increasing concentrations of magnesium and calcium. Calcium pyrophosphate (dissociation constant Kd = 1.9 microM) inhibited pyrophosphatase by competition with magnesium pyrophosphate (Kd = 50 microM). The small movements of calcium detected in mitochondria from yeast may be physiologically significant for the control of inorganic pyrophosphatase activity and the concentration of pyrophosphate in the matrix of yeast mitochondria.
Calcium↗
Imaging features of crystal-induced arthropathy.
Crystal-induced arthropathies constitute a spectrum of inflammatory arthritides that is induced by cellular reaction to crystal deposition in and around joints. A variety of microcrystals may be deposited and can induce an inflammatory response. The three most common types of crystal-induced arthropathy are gout, calcium pyrophosphate dihydrate deposition disease, and calcium hydroxyapatite deposition disease. Each has a characteristic clinical presentation, crystal type that may be aspirated from affected tissues, and radiographic appearance. Each of these entities may occur as a primary abnormality or secondary to an underlying disorder. Sometimes these diseases may coexist in the same joint or individual. Imaging frequently plays a crucial role in the diagnosis of crystal-induced arthropathies and may help to monitor disease progression and treatment response.
Arthrography↗
Calcium phosphate particle induction of metalloproteinase and mitogenesis: effect of particle sizes.
Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals [hydroxyapatite (HA), octacalcium phosphate, tricalcium phosphate] are common in osteoarthritis knee effusions, and are often associated with low-grade synovial proliferation and inflammation. Calcium-containing crystals including HA, are known to have a number of biologic effects on culture cells such induction of mitogenesis, stimulation of Prostaglandin E2 (PGE2) production via the phospholipase A2/cyclo-oxygenase pathway, activation of phospholipase C and inositol phospholipid hydrolysis, induction of metalloproteinase synthesis and induction of proto-oncogenes (c-fos and c-myc). While endocytosis of HA particles is prerequisite of the mitogenic effect of calcium-containing crystals in fibroblasts, it is not known whether endocytosis is required for crystal-induced metalloproteinase synthesis. In the present series of experiments, we examine the effect of three different sizes (106, 46, and 17 microns mean diameters) well-characterized spherical HA particles on the induction of mitogenesis and metalloproteinase synthesis on human fibroblasts. We showed that endocytosis is required for HA particles to induce synthesis of metalloproteinases.
Biocompatible Materials↗
[Crystal-associated destructive arthropathy of the shoulder].
Crystal-associated destructive arthropathy of the shoulder is most commonly observed in elderly women. Functional impairment and social impact define its importance especially in this group. Clinical features include pain at rest and on use, large cool effusion and instability. Radiographs show attrition of bone and cartilage with a paucity of reparative changes. Synovial fluids are viscous, with low cell counts, and stain positively for the presence of apatite-containing particles and often also for calcium-pyrophosphate crystals.
Aged↗
Synovial fluid pyrophosphate and nucleoside triphosphate pyrophosphatase: comparison between normal and diseased and between inflamed and non-inflamed joints.
Deposition of intra-articular calcium pyrophosphate is associated with both aging and arthropathy; increased concentrations of free pyrophosphate (PPi) may contribute to such deposition. Free pyrophosphate and nucleoside triphosphate pyrophosphatase (NTPase) were estimated in synovial fluids from 50 subjects with normal knees and from 44 patients with rheumatoid arthritis, 61 with pyrophosphate arthropathy, and 59 with osteoarthritis. For arthropathic knees clinically assessed inflammation was classified as active or inactive using a summated score of six clinical features. The order of PPi (mumol/l) and NTPase (mumol PPi/30 min/mg protein) was pyrophosphate arthropathy greater than osteoarthritis greater than rheumatoid arthritis (median PPi, NTPase respectively: for pyrophosphate arthropathy 15.9, 0.45; for osteoarthritis 9.3, 0.25; for rheumatoid arthritis 4.4, 0.18), with significant differences between all groups. In pyrophosphate arthropathy both PPi (mumol/l) and NTPase (mumol PPi/30 min/mg protein) were higher than normal (15.9, 0.45 v 8.6, 0.2 respectively), but findings in osteoarthritis did not differ from normal. The inflammatory state of the knee had a distinct but variable effect on synovial fluid findings in rheumatoid arthritis and pyrophosphate arthropathy, but not in osteoarthritis. There was no correlation of either PPi or NTPase with age, or between PPi and NTPase in any group. This study provides in vivo data for synovial fluid PPi and NTPase. It suggests that factors other than PPi need to be considered in a study of crystal associated arthropathy. Clinical inflammation, as well as diagnosis, is important in synovial fluid studies.
Adult↗
Pathological studies on calcification of the intervertebral discs.
Calcified deposits in the intervertebral discs of 35 cadavers microradiographically appeared as linear of flake-like densities composed of calcium pyrophosphate dihydrate (CPPD) crystals and as multiple punctates possibly composed of dicalcium phosphate dihydrate (DCPD) crystals. Calcium deposits were found in 57% of the cadavers by microradiography and 63% by light microscopy, without known metabolic or familial history related to articular chondrocalcinosis. By scanning electron microscopy, CPPD crystals were mainly rod-like, rectangular and cuboid and were about 4 to 10 mu in length while DCPD crystals were prismatic and about 20 to 60 microns in length.
Adolescent↗
[The synovial membrane in articular chondrocalcinosis. Clinico-pathological data].
The study of 25 samples of synovial membrane taken from 118 subjects with articular chondrocalcinosis makes it possible to identify three histological aspects : the complete forms showing a crystalline deposit of calcium pyrophosphate of variable volume and alterations of an inflammatory or degenerative type ; incomplete forms showing no calcium deposit, but in which one can observe two sorts of modifications : forms of chondroid metamorphism or inflammatory stigmatas causing an indeterminate chronic synovitis ; finally, forms of superficial fibrosis of the chorion are sometimes encountered. In all, the synovial membrane in articular chodrocalcinosis is often little different from an arthrosic or senile one. However, the presence of crystalline deposits rich in calcium and phosphorous and varying in size can, in the face of certain articular manifestations of uncertain cause, point to the existence of an articular chondrocalcinosis.
Calcium Pyrophosphate↗
Pseudogout associated with meniscal cysts - report of two patients.
Two patients with pseudogout developed large meniscal cysts at the knee. In the first case the diagnosis of meniscal cyst was confirmed surically. In the second case, the cyst resolved following thorough aspiration. Polarized microscopy of repeated aspirated from cyst in this case as well as of fluids from the knees of both patients consistently showed positively birefringent rhomboid crystals. X-ray diffraction of fluids from the knee of the second patient identified the crystals as calcium pyrophosphate dihydrate.
Aged↗