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Pseudoseptic inflammatory knee effusion caused by phagocytosis of sickled erythrocytes after fracture into the knee joint.

A 57-year-old black man with sickle cell disease was admitted to the hospital because of a painful crisis. After a fall with a fracture into the right knee joint, he developed an acutely painful, swollen knee. Synovial fluid from the right knee showed leukocyte counts of up to 154,000/mm3 and was negative for urate and calcium pyrophosphate dihydrate crystals. Gram stains and cultures were negative. Some sickled red cells were seen by light microscopy; electron microscopy revealed crystal-like arrays of sickled hemoglobin tactoids in erythrocytes which were enfolded and phagocytized by the cells of the synovial fluid. We suggest that this phagocytosis of sickled red cells is the likely cause for the otherwise unexplained inflammation.

Arthritis↗

Transglutaminase activity in aging articular chondrocytes and articular cartilage vesicles.

OBJECTIVE: Transglutaminases (TGases) (E.C. 2.3.2.13) catalyze a posttranslational modification of proteins and are associated with biomineralization in growth plate cartilage. Type II TGase participates in the activation of latent transforming growth factor beta (TGFbeta), a crucial factor for both normal cartilage mineralization and the pathologic mineralization that results in calcium pyrophosphate dihydrate (CPPD) crystal formation in aging articular cartilage. To explore a possible association between TGase levels and CPPD crystal formation in mature articular cartilage, TGase activity in articular chondrocytes from old and young pigs and in the articular cartilage vesicle (ACV) fraction of porcine articular cartilage was examined. In addition, the effects of TGase inhibitors on the production of inorganic pyrophosphate (PPi), a process necessary for CPPD crystallogenesis, were determined. METHODS: TGase activity was measured with a radiometric assay in cultured articular chondrocytes from the knee joints of old (3-5 years old) and young (2-6 weeks old) pigs and in the ACVs. PPi levels were measured in chondrocyte-conditioned media in the presence of TGase inhibitors or control compounds. RESULTS: Levels of TGase activity in the cytosolic fraction of old chondrocytes were 7-fold higher than those in identically cultured young chondrocytes. The mean +/- SD activity level in the membrane fraction of lysed chondrocytes was 6.0 +/- 0.6 units/mg protein in old articular chondrocytes and was undetectable in young chondrocytes. In ACVs, the mean +/- SD TGase activity level was 1.23 +/- 0.1 units/mg protein. Type II TGase protein was present in chondrocyte cytosol and in ACVs. TGase activity was increased by TGFbeta to 120% of control values (P < 0.01), and decreased by insulin-like growth factor 1 to 80% of control values (P < 0.01). TGase inhibitors blocked media accumulation of PPi, an essential precursor of CPPD crystal formation, and a sensitive marker of TGFbeta effect. CONCLUSION: These data suggest a potential link between TGase activity and processes of pathologic biomineralization that result in CPPD crystal formation in aging articular cartilage.

Aging↗

On the feasibility of phosphate glass and hydroxyapatite engineered coating on titanium.

In this report, bioactive calcium phosphate (CaP) coatings were produced on titanium (Ti) by using phosphate-based glass (P-glass) and hydroxyapatite (HA), and their feasibility for hard tissue applications was addressed in vitro. P-glass and HA composite slurries were coated on Ti under mild heat treatment conditions to form a porous thick layer, and then the micropores were filled in with an HA sol-gel precursor to produce a dense layer. The resultant coating product was composed of HA and calcium phosphate glass ceramics, such as tricalcium phosphate (TCP) and calcium pyrophosphate (CPP). The coating layer had a thickness of approximately 30-40 microm and adhered to the Ti substrate tightly. The adhesion strength of the coating layer on Ti was as high as 30-33 MPa. The human osteoblastic cells cultured on the coatings produced by the combined method attached and proliferated favorably. Moreover, the cells on the coatings expressed significantly higher alkaline phosphatase activity than those on pure Ti, suggesting the stimulation of the osteoblastic activity on the coatings. On the basis of these observations, the engineered CaP coating layer is considered to be potentially applicable as a hard tissue-coating system on Ti-based implants.

Durapatite↗

Mitogenic activity of hydroxyapatite: requirement for somatomedin C.

Synovial hyperplasia is a feature of the chronic synovitis associated with basic calcium phosphate crystals [hydroxyapatite (HA), octacalcium phosphate, tricalcium phosphate] and calcium pyrophosphate. Each of these crystals stimulated mitosis of cultured human skin fibroblasts or canine synovial fibroblasts in a concentration-dependent fashion. We examined the effect of pure somatomedin C (Sm-C) on HA crystal induced mitogenesis. Confluent cultures of human fibroblasts were rendered quiescent by incubation in the presence of 1% platelet-poor-Sm-C free plasma (PPSCFP) for 24 hours. HA crystals stimulated thymidine incorporation 2.3-fold over control value. Addition of Sm-C significantly augmented the effect of HA crystals (P less than 0.01). Nearly identical effects were observed in the presence of 100 micrograms/ml HA crystals or 15 ng/ml PDGF. Monoclonal antibodies against Sm-C had little effect on the basal 3H thymidine uptake by control cells incubated in 1% PPSCFP but blocked over 50% of the HA crystal or PDGF-induced 3H thymidine incorporation both in the presence or absence of Sm-C. The incomplete blocking suggested either the presence of other "progression" factors, such as insulin-like growth factor II in the conditioned media or the possibility that HA or PDGF in high enough dosage enabled cells to escape their dependence on Sm-C for DNA synthesis.

Cells, Cultured↗

Agonist-specific tyrosine phosphorylation of Cbl in human neutrophils.

The effects of soluble and particulate agonists on the tyrosine phosphorylation levels of the proto-oncogene Cbl in human neutrophils were examined. Experimental conditions allowing the maintenance of Cbl as well as of its tyrosine phosphorylation status were first established. Their use allowed us to observe that Cbl was tyrosine phosphorylated in response to some (FcgammaRII ligation, opsonized bacteria and zymosan, granulocyte-macrophage colony-stimulating factor, monosodium urate, and calcium pyrophosphate microcrystals), but not all (fMet-Leu-Phe, interleukin-8) neutrophil agonists. Cbl was also shown to account for a varying proportion of the 120-kDa phosphoprotein(s) observed in response to the above stimuli. These data establish that Cbl is present in human neutrophils and that its level of tyrosine phosphorylation is modulated by some of these cells' agonists, and in particular by phagocytic particles. Furthermore, the signaling pathways activated by chemotactic factors and the other neutrophil stimuli tested in this investigation diverge at or downstream from the tyrosine phosphorylation of Cbl.

Chemotactic Factors↗

The relation of cyclic AMP levels to phagocytosis and enzyme release in acute inflammation in vivo.

The effect of altering endogenous leucocyte cyclic AMP levels on phagocytosis and lysosomal enzyme release was studied in vivo. Acute pleural exudates were produced in rats using either calcium pyrophosphate dihydrate crystals or rat serum. Despite marked increases in leucocyte cyclic AMP concentration produced by injection of dibutyryl cyclic AMP and theophylline, there was no reduction in crystal phagocytosis or in enzyme discharge.

Acid Phosphatase↗

Case report 772. Stress fracture of the hip secondary to renal osteodystrophy and erosion of ischium due to amyloid deposition.

We have reported the case history of a 72-year-old woman who was on hemodialysis for 15 years. Her course was marked by many of the musculoskeletal complications of ESRD including CTS, stromal amyloid deposition of synovium, amyloid cystic degeneration of bone, and inflammation of the synovium due to the deposition of calcium oxalate and calcium pyrophosphate microcrystals. She also had evidence of metabolic bone disease: moderate osteoporosis related to secondary hyperparathyroidism and osteomalacia related to aluminum deposition at the mineralization front. The pathological and radiological findings associated with her bone disease are described.

Aged↗

Computed tomography with multiplanar reformation and three-dimensional image reconstruction in the preoperative evaluation of adult hip disease.

Computed tomography (CT) with multiplanar reformation and three-dimensional (3D) image reconstruction was used pre-operatively to outline the bony morphological changes and femoral-acetabular relationships in 25 adult patients suffering from hip disease. Diagnoses included ischaemic necrosis of the femoral head, osteoarthritis, rheumatoid arthritis, calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, previous trauma and chronic dislocation. Polyethylene models of the femora and acetabula were constructed from three-dimensional contouring of CT data and compared with resected specimens in patients subjected to subsequent total hip arthroplasty. Information provided by this imaging technique was useful in both selecting and guiding the most appropriate surgical procedure and it was found that models depicted the actual bony contours with reasonable accuracy. CT combined with multiplanar reformation and 3D analysis may be the optimal pre-operative means of assessment of the diseased adult hip.

Acetabulum↗

Acute popliteal artery occlusion after total knee arthroplasty.

We describe the case of a 71-year-old man with calcium pyrophosphate dihydrate crystal deposition disease who developed acute popliteal artery occlusion immediately after total knee arthroplasty. Reperfusion was achieved thanks to the early diagnosis and thrombolytic therapy with urokinase. Arterial occlusion occurring after total knee arthroplasty is a rare but serious complication. Detailed preoperative evaluation of the peripheral arterial circulation and an early diagnosis seem to be important.

Acute Disease↗

Differential in vivo effects of indomethacin, ibuprofen, and flurbiprofen on oxygen-dependent killing activities of neutrophils elicited by acute nonimmune inflammation in the rat.

The effects of oral administration of various doses of indomethacin, ibuprofen, and flurbiprofen were studied in acute nonimmune pleurisy induced by calcium pyrophosphate crystals (CaPP) in the rat. Drug effects on pleurisy development, as measured by the pleural fluid volume, the number of emigrating leukocytes, and the in vitro oxygen uptake and hydrogen peroxide production of elicited polymorphonuclear neutrophils (PMNs) were investigated. Indomethacin (1.5, 3, and 6 mg/kg) induced a dose-dependent reduction of both exudate volume and number of emigrating leukocytes which reached approximately 50% of control values. A similar inhibition of these two inflammation parameters was observed for the three doses of ibuprofen (6, 18, and 54 mg/kg) and flurbiprofen (0.5, 1.5, and 4.5 mg/kg). The ability of elicited neutrophils to consume oxygen upon stimulation by serum-treated zymosan particles (STZ) was not altered in PMNs derived from animals treated with indomethacin or flurbiprofen, whereas a 35% decrease was induced by ibuprofen. Ibuprofen, but not indomethacin or flurbiprofen, also impaired STZ-induced PMN production of hydrogen peroxide. Furthermore, this inhibition was inversely related to ibuprofen doses. These data indicate that, in addition to their common properties to reduce leukocyte emigration at inflammatory sites, certain NSAIDs such as ibuprofen, but not flurbiprofen or indomethacin, impair particle-induced oxygen-dependent killing activities of elicited PMNs.

Animals↗

Pseudogout in a young patient.

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is conventionally classified into cases that are hereditary, idiopathic (sporadic) or associated with other disorders. In the idiopathic form, the disease usually occurs in middle-aged or elderly patients. An earlier age of disease onset is observed in the hereditary form and the form associated with other disorders. Therefore, the occurrence of CPPD crystal deposition disease in a young patient merits thorough investigation for an underlying cause such as haemochromatosis, hyperparathyroidism, Wilson's disease, hypophosphatasia or hypomagnesaemia and requires a family study to investigate a possible hereditary cause. We report a case of a young female patient who presented with pseudogout at the age of 24 years; no associated diseases or familial occurrence were found despite a follow-up of more than 12 years.

Adult↗

In vitro and in vivo effects of piroxicam on rat polymorphonuclear responsiveness after induction of two acute non-specific inflammatory reactions.

The effect of piroxicam on rat polymorphonuclear leucocytes (PMN) has been studied in vitro and in vivo after the induction of two acute, non specific inflammatory reactions (pleurisies induced by calcium pyrophosphate crystals (CaPP) or isologous serum). An inhibition of chemotaxis by piroxicam has been demonstrated by two techniques, the filter and agarose assays in vivo and in vitro. An inhibition of random cell migration has been observed only at the higher drug concentration using agarose assay with CaPP-elicited cells. Piroxicam also inhibited superoxide anion generation and O2 consumption of CaPP- and serum-elicited cells. These findings suggest that piroxicam may have a direct effect on PMN responses and that this activity could, at least in part, contribute to its anti-inflammatory properties.

Acute Disease↗

Antrafenine: anti-inflammatory activity with respect to oedema and leucocyte infiltration in the rat.

Antrafenine effectively suppressed carrageenan paw oedema in the rat (ED 40 = 24 mg/kg p.o) in the dose range of 10-40 mg/kg p.o, approximating that of phenylbutazone. Antrafenine was superior to phenylbutazone with respect to inhibition of exudate volume and total leucocyte infiltration in carrageenan and calcium pyrophosphate dihydrate crystal pleurisies. The effect of antrafenine on leucocytes was most striking, significant suppression being observed at each dose tested (10, 20, 40 mg/kg p.o), whereas phenylbutazone showed significant activity only at the relatively elevated dose of 40 mg/kg p.o. These observations suggest that antrafenine merits further investigation with respect to its anti-inflammatory effects.

Animals↗

Anti-inflammatory models in animals.

The pleural cavity of rats and guinea-pigs has been utilized to study the inflammatory response to immediate hypersensitivity, delayed hypersensitivity, calcium pyrophosphate and carrageenan. The mediators will be described and their possible interaction with cyclic AMP. Finally the effect of some anti-inflammatory agents on these models will be discussed.

Animals↗

Pharmacological mediators of various immunological and non-immunological inflammatory reactions produced in the pleural cavity.

Intrapleural exudates have been produced in rats and guinea-pigs using calcium pyrophosphate, cell mediated immunity, reversed passive Arthus reaction and carrageenan. The intracellular concentration of various pharmacological mediators has been measured at different times during the evolution of these inflammatory responses. These have been correlated with volume of exudate and cellular migration. The significance of these findings has been discussed and the possible application to the search for new anti-inflammatory agents and their use in diagnostic procedures.

Animals↗

Studies on cell motility in inflammation. I. The chemotactic activity of experimental, immunological and non-immunological, inflammatory exudates.

The accumulation of leucocytes at the site of inflammation may be brought about by chemotaxis or proliferation in the extravascular tissues. The present paper focuses on the chemotactic properties of different types of experimental inflammatory pleural exudates, using a modified Boyden chamber. The time-course of carrageenan-induced exudate chemotactic activity for polymorphs was maximal at 4 h, thereafter diminishing towards 24 and 48 h. Chemotactic activity for mononuclear cells remained unchanged throughout the 4--48 h time-course. Heating the exudates to 56 degrees C for 1 h partially reduced chemotactic activity. These results correlate well with the migration of polymorph and mononuclear cells into the pleural cavity during carrageenan-induced pleurisy. The potency of polymorph and mononuclear cell chemotactic activity of different exudates was of the following order: carrageenan greater than calcium pyrophosphate greater than reverse passive Arthus greater than dextran. The results are discussed in order to elucidate the differences between the underlying mechanisms responsible for leucocyte accumulation in different types of inflammatory reaction.

Animals↗