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PubMed1976

Formation of crystalline deposits by several genera of the family Enterobacteriaceae.

Several species of bacteria from the family Enterobacteriaceae formed crystalline materials containing calcium when grown in a defined culture medium. Enterobacter aerogenes, Proteus vulgaris, Citrobacter freundii, and C. intermedius produced calcium pyrophosphate crystals. Edwardsiella tarda and Escherichia coli formed calcite III crystals, whereas Proteus mirabilis, Klebsiella pneumoniae, Providencia stuartii, and Serratia marcescens produced hydroxyapatite crystals. Several of these bacteria have been isolated from the kidneys of patients with kidney stones, indicating that microorganisms may be involved in the enucleation process of kidney stone formation.

Calcium Carbonate↗

PubMed1995

Transmission electron microscopy observations at the interface of bone and four types of calcium phosphate ceramics with different calcium/phosphorus molar ratios.

Four kinds of 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 molar ratios were 1, 1.5, 1.66 and 2, respectively. Particles (150-300 microns) of these ceramics were packed into holes (diameter 2.5 mm) made in the tibial metaphysis of mature male rats. At 2 weeks, 4 weeks, 8 weeks and 6 months after the operation, undecalcified specimens were prepared. Transmission electron microscopy showed that the bone-bonding behaviour of calcium phosphate ceramics at the interface with bone did not vary with the calcium/phosphate molar ratio. Amorphous substances or needle-like microcrystals were observed on the surface of the ceramics at 2 weeks after implantation. The ceramics showed direct continuity with small crystallites of bone tissue at 4 weeks, 8 weeks and 6 months after implantation. The ceramics appeared to be getting smaller with time. Collagen fibres were not observed at the bone/ceramic interface. Neither chemical bonding nor mechanical bonding by interlocking between bone and ceramics was described by morphological observation using transmission electron microscopy.

Animals↗

PubMed2001

Calcium crystal-induced inflammation.

Recent studies have added to our knowledge regarding the mechanisms of calcium crystal deposition. Calcium pyrophosphate dihydrate (CPPD) crystal deposition is associated with elevated levels of PPi in joints. Cyclic compression of cartilage transiently elevated ATP levels in culture media. Extracellular ATP may be hydrolyzed by nucleoside triphosphate pyrophosphohydrolase (NTPPPH), yielding an elevated PPi concentration. CPPD crystal deposition increases with age. Nitric oxide may alter cartilage matrix by interfering with chondrocyte mitochondrial function and ATP production. Transglutaminase in adult, but not young, porcine articular chondrocytes was able to activate latent transforming growth factor beta, a potent stimulus to PPi production. Basic calcium phosphate crystals are more likely to form in a milieu of reduced PPi concentration. The ank gene mutation results in higher intracellular PPi concentration and lower extracellular concentration. The ANK protein is thought to be a transmembrane protein necessary for transport of PPi out of cells. A mutation that results in reduced synthesis of NTPPPH PC-1 caused infantile wrist and ankle periarticular calcification and vascular calcification.

Animals↗

PubMed1990

Development and evaluation of a method for preservation of synovial fluid wet preparations for quality control testing of crystal identification.

We describe a technique for embedding drops of fresh synovial fluid in mounting resin to prepare test slides that retain crystal morphology for at least 2 weeks. Hospital and private rheumatologists were solicited nationwide to test themselves and their staff with 5 unknown specimens. Eighty-nine percent identified monosodium urate (MSU) crystals from a tophus but only 71% identified smaller and less frequent MSU. Seventy-five percent correctly identified calcium pyrophosphate dehydrate and 42% detected steroid crystals. Apatite crystal clumps included as control slides with no birefringent material were suspected by only 7%. This or another method which simulates actual practice by also testing the equipment and handling of the microscope is proposed as an important component of quality control testing programs for synovianalysis.

Birefringence↗

PubMed1975

Inorganic pyrophosphate pool size and turnover rate in arthritic joints.

Recent studies have shown elevated inorganic pyrophosphate (PPi) levels in most knee joint fluid supernates from patients with pseudogout (PG) or osteoarthritis (OA) and more modestly elevated levels in some supernates from patients with gout or rheumatoid arthritis (RA) relative to PPi levels found in the venous blood plasma of normal or arthritic subjects. We measured the intraarticular PPi pool and its rate of turnover to better understand the significance of the joint fluid-plasma PPi gradient. Preliminary studies in rabbits showed that (32-P)PPi passed from joint space to blood and vice versa without detectable hydrolysis. Incubation of natural or synthetic calcium pyrophosphate dihydrate (CPPD) microcrystals with synovial fluid in vitro in the presence of (32P)PPi tracer showed no change in PPi specific activity in the supernate over a 19-h period so that exchange of PPi in solution with that in CPPD microcrystals could be ignored. Clearance rates of (32P)PPi and of (33P)Pi, as determined by serially sampling the catheterized knee joints of volunteers with various types of arthritis over a 3-h period, were nearly identical. The (32P)PPi/(32P)Pi was determined in each sample. A mixture of a large excess of cold PPi did not influence the clearance rate of either nuclide. The quantity of PPi turned over per hous was calculated from the pool size as determined by isotope dilution and the turnover rate. The residual joint fluid nuclide was shown to be (32P)PPi. The PPi pool was generally smaller and the rate of turnover was greater in clinically inflamed joints. The mean plus or minus SEM pool size (mu-moles) and turnover rate (percent/hour) in PG knees was 0.23 plus or minus 0.07 and 117 plus or minus 11.9, hydrolysis rate (%/h) to Pi was 27.7 plus or minus 13.2; in OA knees: 0.45 plus or minus 0.26 and 72 plus or minus 9.2, hydrolysis 6.9 plus or minus 0.9; in gouty knees: 0.8 plus or minus 0.41 and 50 plus or minus 11.6, hydrolysis 9.8 plus or minus 2.8; and in RA knees: 0.14 plus or minus 0.14 and 114 plus or minus 35.8, hydrolysis 236 plus or minus 116. PPi turnover (mumoles/hour) correlated with the degree of OA change present in the joint as graded by radiologic criteria irrespective of the clinical diagnosis. Mean PPi turnover in joints with advanced OA was greater than in those with mild or moderate changes (P smaller than 0.001), but the mild and moderate groups showed no significant difference. We conclude that synovial PPi turnover and elevated PPi fluid concentrations are not specific for PG patients, and that these factors alone cannot be the only determinants of CPPD crystal deposition.

Adult↗

PubMed1983

Thrombin and ionophore A23187-induced dense granule secretion in storage pool deficient platelets: evidence for impaired nucleotide storage as the primary dense granule defect.

The secretion of the dense granule constituents ATP, ADP, calcium, pyrophosphate (PPi), and orthophosphate (Pi), and the release of magnesium induced by thrombin and the divalent cation ionophore A23187 have been quantitated directly in gel-filtered platelets from patients with storage pool deficiency (SPD). Both the contents and the maximal amounts of the dense granule constituents secretable by thrombin were decreased in all the patients studied, while the nonsecretable, retained amounts of these substances were identical in SPD and normal platelets. In response to both thrombin and A23187, the amounts of secretable ATP and ADP were strongly correlated in the platelets of individual patients; in contrast, secretable calcium showed no correlation with the nucleotides, and significant amounts of calcium were secreted in the total absence of nucleotide secretion in the platelets of several patients. The contents of magnesium were normal in all patients, and approximately 12% of platelet magnesium was liberated by thrombin in both SPD and normal platelets. A23187 induced the release of up to 70% of the magnesium content of normal platelets, but released significantly less (46%) magnesium from SPD platelets. Platelet aggregation induced by A23187 in platelet-rich plasma was also markedly decreased in SPD platelets. The correlations among secretable dense granule constituents suggest the presence in SPD platelets of abnormal dense granule structures that sequester calcium and other constituents but little or no adenine nucleotides, and are thus consistent with a hypothesis that impaired nucleotide transport and/or storage may be the primary dense granule defect in this disorder. In addition, these results demonstrate that certain responses to A23187 are impaired in SPD platelets.

Adenine Nucleotides↗

PubMed2002

Oxalate crystal deposition disease.

In addition to monosodium urate, calcium pyrophosphate dihydrate, and apatite crystals, oxalate crystals are less often found in synovial fluids in association with acute or chronic arthritis. Oxalate crystal deposition disease is seen in patients with primary hyperoxaluria types 1 and 2 (PH1 and 2) and in patients with end-stage renal disease managed with long-term dialysis. Oxalate crystal deposits are found mainly in kidneys, bone, skin, and vessels, and less often inside the joints. Musculoskeletal and systemic manifestations of oxalate crystal deposition disease may be confused with those observed with the other most common types of crystal deposition diseases. Clinical and radiographic features include calcium oxalate osteopathy, acute and chronic arthropathy with chondrocalcinosis, synovial calcification, and miliary skin calcium oxalate deposits and vascular calcifications that affect mainly the hands and feet. Systemic life-threatening cardiovascular, neurologic, and hematologic manifestations are rare. Genomic DNA studies have identified those genetic defects of PH1 and PH2 that allow a precise early diagnosis. Kidney transplantation has poor outcome as a result of graft oxalosis. Combined liver and kidney transplantation is the treatment of choice in patients with PH1 and advanced renal failure. Pre-emptive isolated liver transplantation is the preferred treatment in patients who develop the disease during infancy with progressive manifestations of oxalosis. These novel findings in the understanding of the molecular and enzymatic aspects of primary hyperoxalurias have provided a more rational basis for the management and prevention of oxalate crystal deposition disease. This information may lead to a better understanding and effective management of other common calcium-containing crystal deposition diseases.

Humans↗

PubMed2004

Advanced bioceramic composite for bone tissue engineering: design principles and structure-bioactivity relationship.

The synthesis of a new resorbable porous bioactive silica-calcium phosphate composite (SCPC) that can be used as a tissue-engineering scaffold for bone regeneration is described. The effects of chemical composition and thermal treatment on crystallization and the mechanism of phase transformation in SCPC were evaluated. In the silica-rich samples, beta-rhenanite (beta-NaCaPO(4)) and alpha-cristobalite (SiO(2)) were the dominant phases after treatment at 800 degrees C. On the other hand, in the calcium phosphate-rich samples, calcium pyrophosphate (Ca(2)P(2)O(7)) was formed in addition to beta-rhenanite and alpha-cristobalaite. X-ray diffraction analyses showed a shift in the 2 theta value of the main peak(s) of all phases indicating the formation of solid solutions. Phase transformation reactions were accompanied by a loss of water molecules that contributed to the formation of pores in the size range 10-300 microm. All SCPC samples adsorbed a significantly higher quantity of serum protein than bioactive glass (p < 0.0001). In addition, the silica-rich SCPC adsorbed a significantly higher amount of serum protein than the calcium phosphate-rich samples (p < 0.003). While the crystallization of amorphous silica into L-quartz significantly inhibited serum protein adsorption, the transformation of L-quartz into alpha-cristobalite solid solution (ss) significantly enhanced protein adsorption. On the other hand, in conjunction with the transformation of brushite (CaHPO(4)) into pyro- and tri-calcium phosphates, there was a significant decrease in protein adsorption. However, as pyro- and tri-calcium phosphates transformed into beta-rhenanite, by thermal treatment, protein adsorption increased markedly. Critical-size bone defects grafted with silica-rich SCPC were filled with new bone and contained minimal residues of the graft material. Bone defects grafted with bioactive glass enhanced new bone formation, however, with very limited resorption. The enhanced resorption of SCPC in vivo correlates well with the higher rate of silica dissolution from SCPC than bioactive glass. The facilitated Si dissolution was associated with rapid bone regeneration in defects grafted with SCPC. The enhanced bioactivity properties of the SCPC are due to its chemical composition, modified crystalline structure, and high porosity. The new SCPC may be used for a wide variety of applications in the field of bone reconstruction including tissue-engineering scaffolds for cell and drug delivery.

Animals↗

PubMed1996

Comparison of matrix vesicles derived from normal and osteoarthritic human articular cartilage.

Articular cartilage matrix vesicles (MVs) from normal human adult articular cartilage were examined for protein and enzyme content and biomineralizing capacity for comparison to MVs derived from human osteoarthritic (OA) cartilage. Femoral condylar and tibial plateau cartilage from each of 9 healthy donors ages 17-37 y was enzymatically digested and serially ultracentrifuged to pellet MV's at 3 x 10(6) g-min. MV protein content, nucleoside triphosphate pyrophospho hydrolase (NTPPPH) specific activity (SA) and capacity for 45Ca precipitation were determined. MV precipitated mineral was examined using Fourier transform infrared spectroscopy (FTIR). Normal human cartilage yields 50% less MV protein/g cartilage than OA cartilage (p < .01). Normal human articular MVs possess 30-70x higher NTPPPH SA than cell-free digest. Mean NTPPPH SAs of MVs derived from normal human cartilage are 3x higher than that of OA MVs (p < .05) and normal MV NTPPPH SA appears to decrease with age (p < .01). Normal human MVs support significantly higher calcium precipitation/mg MV protein in both ATP-dependent (p < .01) and -independent (p = .05) systems. The FTIR spectrum of MV mineral generated in the presence of ATP strongly resembles the standard spectrum for calcium pyrophosphate dihydrate (CPPD). The FTIR spectrum of MV mineral generated without ATP resembles that of carbonate-substituted apatite (AP). The fact that isolated MVs from normal cartilage generate pathologically relevant crystal phases in vitro implies that matrix integrity and substrate availability may be crucial factors in the control of pathologic biomineralization.

Adolescent↗

PubMed2006

Performance of hand radiographs in predicting the diagnosis in patients with early arthritis.

OBJECTIVE: To evaluate the ability of baseline hand radiographs to predict the diagnosis 2 years later in a cohort of patients with early arthritis. METHODS: A total of 258 patients with arthritis onset within the previous year were evaluated. At baseline, all patients underwent a standardized evaluation including laboratory tests and radiographs. Hand radiographs were read by a blinded observer who used a standardized procedure for detecting features of crystal deposition diseases and rheumatoid arthritis (RA). After 30 +/- 11.3 months, the final diagnosis was established by a panel of rheumatologists. All radiographs were evaluated. RESULTS: Significant associations were found between radiographic features and a clinical diagnosis of RA, calcium pyrophosphate dihydrate (CPPD) arthritis, and hydroxyapatite arthritis. No radiographic abnormalities suggesting psoriatic arthritis or gout were seen. The sensitivities of hand radiographs for diagnosing CPPD or hydroxyapatite arthritis ranged from 80% to 100%. Baseline hand radiographs suggested the final diagnosis in 31/258 patients, including 21 (22.5%) of the 93 patients with RA, 10 of the 11 (91%) patients with CPPD or hydroxyapatite deposition disease, and none of the patients with other disorders. Sensitivity was 29%, specificity 86.5%, positive predictive value 61%, and negative predictive value 63%. CONCLUSION: In our cohort of patients with recent arthritis, the overall performance of hand radiographs in predicting a diagnosis 2 years later was modest. However, they had an excellent diagnostic value for calcium deposition diseases.

Arthritis, Rheumatoid↗

PubMed1997

Molecular cloning and expression of a porcine chondrocyte nucleotide pyrophosphohydrolase.

The porcine 127-kDa nucleotide pyrophosphohydrolase (NTPPHase) had been previously purified from the conditioned culture media of porcine articular cartilage. Protein sequencing of an internal 61-kDa proteolytic fragment of NTPPHase (61-kDa NTPPHase) determined the 26 N-terminal amino acids. This sequence was used to amplify a DNA fragment, which was used as a probe to clone the gene encoding the 61-kDa NTPPHase from a porcine chondrocyte cDNA library. DNA sequence analysis showed the cDNA insert to be 2509 bp, corresponding to a predicted open reading frame (ORF) encoding 599 amino acids. The 26 N-terminal amino acids of the 61-kDa NTPPHase were located within the ORF immediately downstream of a putative protease recognition region, RRKRR. This is consistent with this cDNA insert representing an internal proteolytic fragment of the full length 127-kDa NTPPHase. BLAST and FASTA analysis confirmed that the deduced amino acid sequence of 61-kDa NTPPHase was unique and did not possess a high degree of homology to sequence in the non-redundant protein and nucleotide databases. Proteins that possess limited homology (< 17%) with the 61-kDa NTTPPHase include several prokaryotic and eukaryotic ATP pyrophosphate-lyases (adenylate cyclase). Northern blot analysis of porcine chondrocyte RNA showed that the DNA encoding the 61-kDa NTPPHase hybridized to a single 4.0-kb RNA transcript. This DNA probe also hybridized to a single species of human chondrocyte RNA. Expression of a 61-kDa protein was detected by coupled in-vitro transcription/translation. Western blot analysis of this in-vitro transcription/translation reaction detected a 61-kDa protein, using an antibody raised against the peptide sequence that was originally used to clone the 61-kDa NTPPHase. These data indicate the successful in-vitro cloning and expression of the porcine chondrocyte 61-kDa NTPPHase. Future studies that utilize the gene encoding the 61-kDa NTPPHase may allow the characterization of the role of NTPPHase in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease.

Amino Acid Sequence↗

PubMedDate not supplied

Pseudogout in ochronosis. Report of a case.

Calcium pyrophosphate dihydrate crystals were identified in synovial fluid white blood cells during an episode of acute arthritis in a patient with ochronosis and chondrocalcinosis. Review of the histories and radiographs of 5 other patients with ochronosis demonstrated two additional instances of chondrocalcinosis. Both of these patients had episodes of arthritis consistent with pseudogout. This suggests that pseudogout, which has been found in increased incidence in some metabolic diseases, may also be more common in ochronosis.

Arthroplasty↗

PubMed1996

Association between synovial fluid levels of inorganic pyrophosphate and short term radiographic outcome of knee osteoarthritis.

OBJECTIVE: To test the hypothesis that high concentrations of extracellular inorganic pyrophosphate (PPi), which associate with increased cell synthesis and turnover in cartilage, may act as a marker for structural outcome in knee osteoarthritis (OA). METHOD: One hundred and thirty five consecutive patients referred to hospital with knee OA (59 men, 76 women; mean age 71 years, range 41-88) were followed prospectively for a median of 2.5 years (interquartile range 1.75-3.0). Synovial fluid (SF) aspirated at presentation (202 OA knees: 68 bilateral, 66 unilateral) was assessed for PPi content by radiometric assay. Knee radiographs at presentation and at final review were assessed for change in global (Kellgren) and individual features (narrowing, osteophyte, sclerosis, cyst, attrition) of OA. RESULTS: The median SF PPi level was 10.5 mumol (range 0.07-72.4). At baseline, high PPi was significantly associated with presence of calcium pyrophosphate crystals, chondrocalcinosis, and bone attrition. Radiographic change was observed in 164 knees. High PPi levels were negatively associated with change in Kellgren and Lawrence grade, further narrowing, and increase in osteophyte, but positively associated with development of attrition. In the 68 patients from whom bilateral data were obtained, there was correlation between right and left knees for PPi levels, all baseline radiographic scores, and changes in radiographic features. Multiple logistic regression analysis for PPi as a continuous variable (age, gender, and patient number included in model) showed a negative correlation with change in global Kellgren and Lawrence grade (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95 to 0.99) and a positive correlation with attrition (OR 1.04, 95% CI 1.02 to 1.07). CONCLUSION: High SF levels of PPi are associated with favourable radiographic outcome in terms of progressive change in Kellgren grade. Such elevated PPi levels, however, may inhibit new bone formation and remodelling in knee OA.

Adult↗

PubMed1977

Stimulation of sugar uptake and thymidine incorporation in mouse 3T3 cells by calcium phosphate and other extracellular particles.

Evidence is presented that the marked stimulation of sugar uptake and thymidine incorporation by addition of extra Ca2+ to stationary phase mouse 3T3 cells in culture is phosphate dependent and due to the action of the calcium phosphate precipitate formed in the medium. The cells are similarly stimulated by a variety of particulate materials, including calcium pyrophosphate, barium sulfate, kaolin, and polystrene beads. The precipitate effects on sugar uptake are of the same magnitude as those seen with certain hormones (insulin, epidermal growth factor) or with fresh 10% calf serum. The effect of barium sulfate on thymidine incorporation is also of the same magnitude as seen with these hormones, but much less than half that found with fresh calf serum. The stimulation by barium sulfate or hormones of thymidine incorporation is not phosphate dependent.

Barium Sulfate↗

PubMed1983

Activation of the alternative pathway of complement by monosodium urate monohydrate crystals and other inflammatory particles.

Activation of serum C3 by monosodium urate monohydrate (MSU) crystals and other particles was determined by immunofixation following electrophoretic separation of C3 and its activation products. Densitometry allowed quantitation of results. MSU, hydroxyapatite, brushite, and calcium pyrophosphate dihydrate crystals split C3 under conditions which demonstrate activation via the alternative pathway (AP). Quantitatively similar results were obtained in immunoglobulin deficient serum. Activation was crystal specific and was reduced by heating, grinding, sonication, and aging of crystals. Other inflammatory particles (e.g., blackthorn) activated C3 via the AP: noninflammatory particles (e.g., diamond) caused insignificant activation. It is suggested that particle-induced activation of the alternative pathway of complement may be important in the initiation of crystal-induced synovitis.

Agammaglobulinemia↗

PubMed1993

Inhibition of tyrosine phosphorylation by wortmannin in human neutrophils. Dissociation from its inhibitory effects on phospholipase D.

BACKGROUND: Recent studies have indicated that the regulation of the activation of human neutrophils depends on tyrosine phosphorylation and on phospholipase D. Furthermore, a tentative causal relationship between these two signalling pathways has been indirectly implied derived through the use of inhibitors of tyrosine kinases. The fungal metabolite, wortmannin is at present the only compound known to inhibit the receptor-mediated activation of phospholipase D in human neutrophils. Its mechanism of action is presently unknown. EXPERIMENTAL DESIGN: The ability of peripheral blood neutrophils to respond to various agonists with an increase in activity of phospholipase D and an enhancement of tyrosine phosphorylation in the absence or presence of wortmannin was monitored. RESULTS: Wortmannin was found to inhibit the stimulation of tyrosine phosphorylation by fMet-Leu-Phe, and by the inflammatory microcrystals monosodium urate and calcium pyrophosphate dihydrate. This effect of wortmannin was not secondary to inhibition of phospholipase D as U73122, a previously described phospholipase C inhibitor, was also found to inhibit phospholipase D without affecting tyrosine phosphorylation. CONCLUSIONS: The results make it likely that one of the earliest sites of action of wortmannin in human neutrophils is at the level of tyrosine phosphorylation which then exerts a modulatory influence on the activation of phospholipase D.

Androstadienes↗

PubMed1991

Prevalence of chondrocalcinosis in patients with primary hyperparathyroidism in Japan.

One hundred and thirty-two consecutive patients with primary hyperparathyroidism were studied preoperatively for the presence of chondrocalcinosis, the roentgenographic marker of calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, by obtaining radiographs of knees, wrists and pelvis. Chondrocalcinosis was found in 8 patients (6.1%), each of whom was over 50 years of age. In 72 of the patients over 50 years of age, the prevalence of chondrocalcinosis in the hyperparathyroid patients (11.1%) was greater than that found in 72 control patients (2.8%) with thyroid nodular disease who were exactly matched for age and sex, but the difference was not significant. The prevalence of chondrocalcinosis in the hyperparathyroid patients sharply increased with age. In the group in their 50's it was 4.4%, rising to 15.8% in patients in their 60's and reaching 37.5% for those over 70 years of age. Patients with chondrocalcinosis were significantly older than those without this finding (p < 0.005). Those with chondrocalcinosis also had significantly higher preoperative serum calcium levels than those without it (p < 0.05). While chondrocalcinosis was detected by taking joint radiographs in all patients with primary hyperparathyroidism, acute arthritis (pseudogout attack) occurred in only 2 of the 132 patients (1.5%) after parathyroidectomy, but this represents 25% (2 of 8) of those who had chondrocalcinosis. An attack of pseudogout may therefore be one of the most common postoperative complications of parathyroid surgery in the elderly. Considering the low incidence of pseudogout attack following parathyroidectomy, preoperative radiological studies of the knee joints are sufficient to screen for chondrocalcinosis and are recommended for patients over 60 years old in Japan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1966

Crystal-induced inflammation in canine joints. I. An experimental model with quantification of the host response.

Injection of sodium urate or calcium pyrophosphate crystals into the stifle joints of anesthetized dogs almost invariably induced an acute exudative response. This response was quantified by serial measurements of intra-articular pressure, pH and leukocyte concentration. Pressure rose progressively and reflected intra-articular volume increase. The hydrogen ion concentration increased as the reaction progressed and correlated in a given exudate with the leukocyte concentration. Analysis of sequential physiologic and biochemical changes occurring in this model of crystal-induced inflammation may provide insight into the mechanisms of acute gouty arthritis in man.

Animals↗