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At least 1,153 records · Page 64Linked to original sources
PubMed2000

The inhibition of spontaneous and tumor necrosis factor-alpha induced neutrophil apoptosis by crystals of calcium pyrophosphate dihydrate and monosodium urate monohydrate.

OBJECTIVE: Spontaneous neutrophil apoptosis may be inhibited by various proinflammatory stimuli. which may result in prolonged lifetimes and responses of these phagocytic cells with the potential for extended inflammation. We investigated the effect of short term incubation of opsonized crystals of monosodium urate monohydrate (MSUM) or calcium pyrophosphate dihydrate (CPPD) on both spontaneous and tumor necrosis factor-alpha (TNF-alpha) induced neutrophil apoptosis. METHODS: Peripheral neutrophils were incubated with plasma opsonized crystals of CPPD or MSUM in the presence or absence of TNF-alpha for 4 h at 37 degrees C. Apoptosis was determined using 3 separate assays: (1) an agarose DNA fragmentation assay, (2) a cytoplasmic histone associated DNA fragmentation assay, and (3) a caspase 3 fluorometric assay. RESULTS: All 3 assays showed similar results. Both MSUM and CPPD crystals inhibited spontaneous apoptosis in neutrophils. TNF-alpha induced high levels of apoptosis in neutrophils. However, co-incubation of the cells with TNF-alpha and crystals resulted in the inhibition of apoptosis to levels below those of control cells. Pretreatment of neutrophils with the protein synthesis inhibitor cycloheximide prevented the inhibition of apoptosis by crystals. CONCLUSION: These data support the concept of crystal induced inhibition of neutrophil apoptosis as part of the pathophysiology of the diseases collectively known as crystal induced arthritis.

Apoptosis↗
PubMed2001

Inhibitory effect of low density lipoprotein on the inflammation-inducing activity of calcium pyrophosphate dihydrate crystals.

OBJECTIVE: It has been proposed that low density lipoprotein (LDL) plays a role in the self-limiting nature of pseudogout inflammation. We investigated changes of LDL concentration in rat air pouch fluid during periods of acute and subsiding inflammation to evaluate whether LDL contributes to inhibiting inflammation of pseudogout. We examined whether LDL binds to calcium pyrophosphate dihydrate (CPPD) crystals as a possible mechanism for reduction of inflammation. METHODS: In this in vivo study, 5 mg suspensions of CPPD crystals and saline were injected into the rat air pouch. Fluid samples were taken from rat air pouch at 0, 3, 6, 12, 24, and 48 h after injection. White blood cells in the samples were counted; the remaining fluid was centrifuged and concentrations of beta-glucuronidase and PGE2 in the supernatant were measured as inflammatory markers. LDL in the supernatant was immunochemically identified by Western blotting, then pellets containing crystals were examined by the same technique. RESULTS: LDL was identified in the air pouch 3 h after CPPD crystal injection, and its concentration increased and reached a peak level after 24 h. Inflammatory markers reached maximal level from 6 to 12 h, then decreased after 24 h. In the pellets containing crystals, LDL could not be identified in every specimen. CONCLUSION: LDL in the rat air pouch increased during the inflammatory course induced by CPPD crystal and the inflammation subsided as the LDL increased. Since some reports indicate LDL was related to reduction of crystal induced inflammation such as gout or pseudogout, we concluded that LDL could contribute to the resolution of acute pseudogout arthritis in vivo with or without binding to CPPD crystals.

Animals↗
PubMed2001

[Improvement of 99mTc-pyrophosphate scintigraphy in detection of acute myocardial infarction: combined with 99mTc-tetrofosmin].

BACKGROUND: 201Tl and 99mTc-pyrophosphate (PYP) dual scintigraphy is daily used in the detection of acute myocardial infarction (AMI). However, 201Tl is not available on emergent situation. We proposed a new method for detection of AMI combined 99mTc-PYP with 99mTc-tetrofosmin (TF). METHODS: 99mTc-PYP (740 MBq) was administered to 25 patients with AMI, and 3.5 hours later, planar imaging (PYP planar) and SPECT were performed (PYP-SPECT). Immediately after cessation of PYP-SPECT, 99mTc-TF (370-740 MBq) was injected and 5 minutes later SPECT was performed in the same position (TF-SPECT). PYP-SPECT and TF-SPECT were reconstructed in the same geometric status to permit superimpose of PYP-SPECT and TF-SPECT images. Two experts and 2 beginners of nuclear medicine physician interpreted the images in three ways; PYP planar image only, PYP-SPECT, and PYP-SPECT with TF-SPECT. RESULTS: PYP-SPECT combined with TF-SPECT shows 100% detectability of the AMI lesions, which is significantly higher than other two methods in both experts and beginners. CONCLUSION: PYP-SPECT combined with TF-SPECT is a powerful method for detection of AMI.

Aged↗
PubMed2002

Cartilage intermediate layer protein expression in calcium pyrophosphate dihydrate crystal deposition disease.

OBJECTIVE: To elucidate the mechanisms of calcium pyrophosphate dihydrate crystal deposition disease (CPPDCD) in the meniscus, synovium, labrum, tendon, ligament, and soft tissue, we studied the expression of cartilage intermediate layer protein (CILP). METHODS: Histological sections and clinical data from 33 patients who fulfilled the criteria of Ryan and McCarty for CPPD were reviewed. Formalin fixed and paraffin embedded tissue sections of 33 patients with CPPDCD were stained with hematoxylin and eosin (H&E) and alizarin red S. Immunostaining was performed using affinity purified polyclonal antibody to synthetic peptide corresponding to the N-terminal sequence of the 61 kDa domain of porcine CILP. RESULTS: The age of patients ranged from 49 to 89 years (median 73). The knee was the commonest site. Radiologically, almost all lesions exhibited fine, radiopaque, linear deposits in the meniscus, articular cartilage, and synovium or joint capsule. Histopathologically, all cases showed deposits of birefringent monoclinic or triclinic crystals, which were visualized by polarized light microscopy with a red analyzer filter. In alizarin red S staining, more numerous crystals were observed than in H&E staining. Crystal deposition was usually associated with adjacent variable amounts of hypertrophic and/or metaplastic chondrocytes in each type of tissue. Variable intensity of CILP immunostaining was found in deposits of each lesion. Hypertrophic/metaplastic chondrocytes in and around CPPD deposits were also positive for CILP. Small cartilaginous islands remote from the CPPD deposits exhibited a weak positivity for CILP. In addition, weakly positive chondrocytes were noted in a transitional zone between cartilaginous islands with and without the deposits. In addition to cytoplasmic immunoreactivity, immunostaining for CILP was observed in the pericellular fibrous matrix. CONCLUSION: Hypertrophic or metaplastic chondrocytes characteristic of CPPDCD may be directly involved in the formation of CPPD crystals. Our study suggests that increased CILP expression was closely associated with CPPDCD, and might play a role in promoting CPPD crystal formation.

Aged↗
PubMed2002

Evaluation of the effect of mitomycin-C on the bioavailability of technetium-99m-labelled sodium pyrophosphate in mice.

We have reported that drugs alter the biodistribution of radiopharmaceuticals used in diagnostic imaging in nuclear medicine. Knowledge of such altered biodistribution is important in making diagnostic from scintigraphy. Mitomycin-C is used as component of many chemotherapeutic regimens to treat different tumors. The biological activities of mitomycin-C can be explained by its ability to inhibit deoxyribonucleic acid synthesis. Since patients on chemotherapeutic treatment can be submitted to nuclear medicine procedures, we studied the mitomycin-C effect on the bioavailability of the technetium-99m-labelled sodium pyrophosphate (9mTc-PYP) using an animal model. Mitomycin (0.45 mg) was administered by ocular plexus way Balb/c mice. One hour after the last dose, 99mTc-PYP (7.4 MBq) was administered and after 0.5 hr the animals (n = 15) were rapidly sacrificed. The organs were isolated, the radioactivity counted in a well counter and the percentage of radioactivity (%ATI) calculated. The results have shown that in the treated animals the %ATI has been decreased in spleen, thymus, heart and brain and increased in lung, liver and bone. The effect of this chemotherapeutic drug on the 99mTc-PYP biodistribution was statistically significant (Wilcoxon test, p < 0.05) and it could be explained by the metabolization or therapeutic action of mitomycin-C.

Animals↗
PubMed2003

The utility of alizarin red s staining in calcium pyrophosphate dihydrate crystal deposition disease.

OBJECTIVE: To determine the most suitable staining method for preservation and detection of calcium pyrophosphate dihydrate (CPPD) crystals in histological sections of patients with CPPD crystal deposition disease. METHODS: Paraffin sections of CPPD crystal-bearing tissues of 31 patients were stained with hematoxylin and eosin (H&E) and Alizarin red S (ARS). For H&E, the sections were treated with Mayer's hematoxylin (pH 2.3) for 5 min and with eosin alcohol (pH 4.1) for 1 min. For ARS, 1% ARS dissolved in distilled water was adjusted to pH 6.4 by adding 0.1% ammonia solution drop by drop while stirring. As controls, unstained sections were soaked in 1% citric acid monohydrate solution (CAMS, pH 2.3) for 5 or 10 min. The histological preparations were examined under a compensated polarized light using a first-order red compensator. We counted the number of weakly positive birefringent CPPD crystals in 3 high power fields (HPF, 0.272 mm2). RESULTS: CPPD crystals were seen clearly in most specimens stained with ARS, but were markedly reduced in tissue sections stained with H&E or CAMS. The number of CPPD crystals detected in sections stained by ARS (1723 +/- 683 per 3 HPF, mean +/- standard deviation) was significantly higher compared with H&E, CAMS (5 min), and CAMS (10 min) (401 +/- 374, 1022 +/- 616, and 494 +/- 636 per 3 HPF, respectively; p < 0.001, each). CONCLUSION: Standard H&E staining reduces the number of visible CPPD crystals, probably due to the strong acidity of both hematoxylin and eosin solutions, whereas the ARS stain seems to preserve a large number of CPPD crystals. The utility of ARS staining may improve the identification of CPPD crystals and contribute to a correct diagnosis of CPPD crystal deposition.

Aged↗
PubMed1992

[Acute myocardial infarction: comparison of results of Tl-201, Tc-99m pyrophosphate and In-111 antimyosin Fab imagings].

To evaluate the extent and characteristics of infarct areas, we performed indium-111 monoclonal antimyosin Fab (InAM), thallium-201 (TL) and Tc-99m pyrophosphate (PYP) imagings in 17 patients with acute myocardial infarction, and tried to find out the mechanism that causes difference of these imagings. In each study, the extent scores as an index of the infarct area were obtained by single photon emission computed tomography (SPECT), and comparisons were made between the results obtained. The overlap between InAM and TL imagings obtained by SPECT was evaluated. Location, severity, extent and patterns of accumulation were compared between InAM and PYP with both planar image and SPECT. The extent scores of InAM correlated well with those of TL (r = 0.73, p < 0.01). However, the overlap of both methods was recognized in 8 of 17 patients, in whom wall thickness of the infarct area as obtained by echocardiography was well preserved. The left ventricular regional asynergy was mild in 6 of these 8 patients. Coronary angiography showed poor or no collateral circulation in these cases. Although there were generally close correlations of the extent scores between InAM and PYP, discrepancy was noted in 2 cases for location; 2 for severity, 5 for extent, and 3 for patterns of accumulation. These differences may be attributed to the timings of imaging, coronary reperfusion and different mechanisms of accumulation. In conclusion, the extent of acute myocardial infarction obtained by InAM correlates well with those obtained by TL and PYP, with some exceptions.

Adult↗
PubMed1992

Comparison of the acute inflammation induced by calcium pyrophosphate dihydrate, apatite and mixed crystals in the rat air pouch model of a synovial space.

Pure monoclinic or triclinic calcium pyrophosphate dihydrate (CPPD) crystals, apatite crystals or mixtures of these crystals were injected into the synovial-like space created by the rat air pouch to compare the acute inflammation induced by these crystals. Fluids were withdrawn 6 h after injection and examined for leukocyte counts, protease, prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) levels. CPPD crystals (especially monoclinic CPPD) induced higher numbers of leukocytes, and more protease, PGE2 and TNF than apatite. CPPD seemed to play a predominant role in the acute inflammation induced by mixed crystals.

Animals↗
PubMedDate not supplied

Calcium pyrophosphate deposition disease: description in defleshed skeletons.

The osseous appearance, skeletal distribution, and distinguishing features of calcium pyrophosphate deposition disease (CPPD) were delineated in a population of 2906 contemporary defleshed skeletons. The limitations of routine x-ray and clinical examination were transcended in this study of defleshed bones. The nature of the disease was clearly identified and preconceived notions (based on the "shades of black and white" of the conventional x-ray technique) were examined on the basis of the actual osseous impact. Epidemiologic assessment of this disease allowed it to be distinguished from rheumatoid and other erosive forms of arthritis. Analysis of the "pseudo-rheumatoid" subgroup of CPPD provided clear criteria for distinguishing the disease from rheumatoid arthritis. Characterization of the nature and epidemiology of osseous alterations in a contemporary skeletal population permitted the development of a standard for recognition of CPPD in skeletal populations and for clarification of the nature of associated pseudo-erosions.

Arthritis↗
PubMed2004

Suicidal dephosphorylation of thiamine pyrophosphate coupled with pyruvate dehydrogenase complex.

Earlier it was noted that purified pyruvate dehydrogenase complex (PDC) produced by "Sigma" usually contains almost saturating amounts of thiamine pyrophosphate (ThPP). In this communication we present the observation that the endogenous ThPP coupled to PDC is dephosphorylated while staying at -10 degrees C, because in the enzyme preparation thiamine monophosphate and un-phosphorylated thiamine appear (HPLC determination). Under the same conditions exogenous ThPP is not dephosphorylated despite contact with the PDC preparation. This may suggest that interactions of some active groups of the enzyme with molecules of endogenous ThPP leads to break-up of the phosphoesters bonds, and destruction of the coenzyme. Decrease of PDC activity during storage is not in proportion with the degree of ThPP dephosphorylation. However the observed instability of PDC activity may be a consequence of the spontaneous process of its coenzyme autodestruction.

Animals↗
PubMed1991

[Right ventricular infarction following acute inferior myocardial infarction confirmed by dual isotope single photon emission computed tomography (SPECT) of [99mTc] pyrophosphate and [201Tl] chloride].

A 56-year-old man, complaining of severe substernal chest pain, was admitted. In this patient, right ventricular infarction following by acute inferior myocardial infarction was suggested by serial enzymes, electrocardiogram, echocardiogram, and hemodynamic data, but it was not confirmed. A dual isotope SPECT with 99mTc-pyrophosphate and 201Tl-Cl was performed and color-coded tomograms were obtained. It showed a characteristic image of right ventricular infarction, especially in the short axis view right ventricular infarction looked like shape of a tongue which protruded from left ventricle. We concluded that though the diagnosis of right ventricular infarction is difficult, a dual isotope SPECT is a useful method because it shows a characteristic image.

Diphosphates↗
PubMed1990

Regulation of 5-phosphoribosyl 1-pyrophosphate and of hypoxanthine uptake and release in human erythrocytes by oxypurine cycling.

Uptake and release of purines by red blood cells has been shown to be markedly sensitive to changes in pH, inorganic phosphate (Pi), and oxygen concentration (Berman, P., Black, D., Human, L., and Harley, E. (1988) J. Clin. Invest. 82, 980-986). The mechanism of this regulation has been further studied. We have shown that incubation of red cells in medium containing xanthine oxidase rapidly and completely depletes intracellular hypoxanthine and causes accumulation of 5-phosphoribosyl 1-pyrophosphate (PRPP) at physiological Pi concentrations. Hypoxanthine release from intracellular IMP is strictly dependent on PRPP depletion, induced by either alkalinizing the cells or by adding excess adenine. Xanthine oxidase abolishes this dependence. Oxygen depletion enhances adenine uptake and prevents hypoxanthine release. The results suggest that hypoxanthine release is governed by PRPP-dependent recycling of hypoxanthine to IMP. We propose that PRPP accumulation in red cells is regulated by a substrate cycle, comprising hypoxanthine, IMP, and inosine. Cycle flux is controlled by Pi inhibition and 2,3-bisphosphoglycerate activation of purine-5'-nucleotidase, which converts IMP to inosine. Oxypurine cycling may account for the sensitive control of purine uptake and release by changes in pH and oxygen tension that occur physiologically.

Biological Transport↗
PubMed1990

Induction of millimolar amounts of 5-phosphoribosyl-1-pyrophosphate in human erythrocytes by incubation in inosine-pyruvate-phosphate medium. A 31P-NMR study.

Incubation of human erythrocytes in inosine (10 mM), pyruvate (10 mM), phosphate (50 mM) and NaCl (75 mM) (IPP-medium)1 at pH 6.6 leads to a ca. 1000 fold increase in the concentration of 5-phosphoribosyl-1-pyrophosphate (PRPP) as identified and measured by 31P-NMR spectroscopy. PRPP accumulation is pH-dependent with a maximum at extracellular pH 6.60 and the maximum value of 1.3-1.6 mmol/l RBC is reached within one hour at 37 degrees C. PRPP accumulated despite high concentrations of 2,3-diphosphoglycerate (2,3-DPG), an inhibitor of PRPP-synthetase. The concentration of PRPP attained correlated with the intracellular concentration of inorganic phosphate (P1). Substitution of either adenosine or adenosine plus inosine for inosine in the medium (APP or A+IPP media) did not lead to NMR detectable accumulation of PRPP, despite the same high concentrations of intracellular P1. The lack of accumulation of PRPP in adenosine containing media may be related to the higher concentrations of nucleoside diphosphates induced in these media. These results show that neither 2,3-DPG nor PRPP itself inhibit the synthesis of PRPP in the human erythrocyte under these circumstances.

Erythrocytes↗
PubMed1977

Protein binding to monosodium urate monohydrate, calcium pyrophosphate dihydrate, and silicon dioxide crystals. I. Physical characteristics.

The protein adsorptive properties of monosodium urate monohydrate (MSU), silica (Si), and calcium pyrophosphate dihydrate crystals were studied by qualitative and quantitative techniques. Immunoglobulin G (IgG) was adsorbed preferentially by MSU crystals from normal human serum and demonstrated high-affinity binding isotherms when compared with several isolated proteins in solution. The physical characteristics of this reaction suggest principally an ionic mechanism, since adsorption was enhanced by decreasing pH or ionic strength. Weaker physical forces also were suggested by studies showing enhanced adsorption at lower temperatures. The following order of affinity for Si or MSU crystals was found when equal concentrations of proteins were compared: Cohn fraction II greater than lysozyme greater than beta lactoglobulin greater than bovine serum albumin greater than ovalbumin. IgG adsorption to the crystals studied may explain certain features of their biological activity. It is suggested that this phenomenon blocks the membranolytic properties of crystals and stimulates their phagocytosis through interaction with Fc receptors on the surface of the phagocytic cells.

Adsorption↗
PubMed1991

Histochemical localization of calcium with potassium pyroantimonate in the articular tissues in calcium pyrophosphate dihydrate crystal deposition disease.

The ultrastructural localization of calcium in the articular cartilage, meniscus, and synovium of patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease was examined by using potassium pyroantimonate. Focal areas with deposition of CPPD crystals in each tissue showed electron-dense precipitates of the antimony-calcium complex: (1) in the cytoplasm of hypertrophic chondrocytes around CPPD crystals, especially on the margins of intracellular lipid droplets or within electron-dense amorphous material or both; and (2) on the margins of lipid droplets and within electron-dense amorphous material in the degenerated matrix surrounding the hypertrophic chondrocytes. The slender rodlike structures consisting of electron-dense precipitates of the antimony-calcium complex, suggestive of the precursor to rodlike CPPD crystals, were also observed in the degenerated matrix. These findings suggest that the hypertrophic chondrocytes may contribute to the formation of CPPD crystals by intracellular accumulation of calcium and subsequent release of high concentration of calcium into their surrounding matrix.

Aged↗
PubMed1992

Coffin-Lowry syndrome associated with calcium pyrophosphate crystal deposition in the ligamenta flava.

Clinical and ultrastructural study of four cases of Coffin-Lowry syndrome (CLS), a heritable disorder with peculiar facies, stooped posture, vertebral changes, and mental retardation, is reported. Three of the four cases had myelopathy caused by calcification of the ligamenta flava in early adulthood. These patients demonstrated that CLS is a calcium pyrophosphate dihydrate crystal deposition disease, and it is postulated that a metabolic abnormality in collagen and in proteoglycans are responsible for some aspects of CLS.

Adolescent↗
PubMedDate not supplied

[A modified method for phosphoribosyl pyrophosphate synthesis].

A modified method for synthesis of phosphoribosyl pyrophosphate (PRPP) from ribose-5-phosphate and ATP in presence of ribose phosphate pyrophosphokinase (RPPPK) was developed. RPPPK was isolated from extracts of acetone powder of rabbit liver tissue, using alcohol fractionation of proteins. The protein fraction, containing RPPPK, was isolated at 35% saturation with 96% ethyl alcohol. The identification of the synthesized preparation of PRPP was carried out in enzymatic reaction with adenine- and inosine phosphoribosyl transferases, using labelled adenine and guanine. The obtained product of reaction (AMP and GMP) were precipitated with lantane chloride.

Animals↗