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PubMed1981

Familial pyrophosphate arthropathy. Occurrence and Crystal Identification.

Hereditary pyrophosphate arthropathy has been observed in three Swedish families and in a few other caucasian populations. The inheritance is most probably autosomal dominant with a variable penetrance. The most severe cases have been found in homozygotes among isolates of immigrants in Slovakia and Chile. Studies on genetic and etio-pathogenetic factors in hereditary pyrophosphate arthropathy, and the utilization of new diagnostic techniques for crystal identification, are important approaches towards a further understanding of the disease.

Adult↗

PubMed1981

Measurement of soluble pyrophosphate in plasma and synovial fluid of patients with various rheumatic diseases.

Soluble pyrophosphate was measured in the plasma and synovial fluid of various groups of patients and in the plasma of two control groups. The two control groups consisted of 13 healthy subjects and 19 patients suffering from benign lumbar back pain. The other group of patients had rheumatoid arthritis (RA) (14 plasma and 19 synovial fluid examinations), osteoarthrosis (OA) (19 plasma and 26 synovial fluids) and articular chondrocalcinosis (ACC) (27 plasma and 43 synovial fluids). The level of soluble pyrophosphate in the plasma was 3.5 mumol/l in healthy subjects, 4.0 mumol/l in patients with lumbar back pain, 4.1 mumol/l in individuals having OA and 3.5 mumol/l in the group suffering from RA as well as for those with ACC. The differences between these values are not significant statistically. In the synovial fluid the values were 4.6 mumol/l for the group with RA, 12.7 mumol/l for those with OA and 34.2 mumol/l in the group having ACC. If a normal distribution of these values is assumed and the average values and standard deviations recalculated for each group after elimination of cases more than 3 standard deviations above the mean, then we obtain 9.8 mumol/l for the group with OA and 23.8 mumol/l for those with ACC. The difference between the group with RA and that with OA is highly significant (p greater than 0.0001). Even more significant is the difference between the group with RA and ACC (p less than 0.0005). The difference between the OA and the ACC is also highly significant (p less than 0.001). On the basis of these observations various mechanisms leading to the pyrophosphage crystal deposition disease are discussed.

Arthritis↗

PubMed1980

Determination of the vitality of the femoral head with 99mTc-Sn-pyrophosphate scintigraphy.

A series of 14 patients who for various reasons were scheduled for total hip replacement were investigated. 99mTc-Sn-pyrophosphate scintigraphy and tetracycline labelling of the bone structure was performed prior to surgery, and subsequently the femoral heads were submitted to histological evaluation on decalcified as well as non-decalcified slides. The evaluation of the scintigraphs was performed by a specialist in nuclear medicine and the histological slides were evaluated by a pathologist, in both cases without reference to the radiological findings or the clinical history. The scintigraphic evaluations of the vitality of the femoral head were in all cases verified by the histological examination, whereas the radiological findings in three cases failed to demonstrate that a femoral head necrosis actually was present. From this study it can be concluded that 99mTc-Sn-pyrophosphate scintigraphy is an excellent method of assessing bone vitality in the femoral head.

Adult↗

PubMed1981

Pyrophosphate arthritis with local amyloid deposition.

Pyrophosphate and capsular chondromatosis were demonstrated histologically in 15 cases, 14 of which also exhibited local deposition of amyloid. A systematic examination of the joint capsule in 57 consecutive hip replacement operations for osteoarthritis revealed these changes in 6 of the cases (10.5 per cent). Microscopic examination which was done if intraarticular calcifications were grossly visible at operation, showed the same changes in 8 knees, 4 with osteoarthritis and 4 with meniscal disease. The changes were also seen in the menisci. Only one patient was suffering from chronic, polyarticular pyrophosphate arthritis. In the other cases neither change had been expected a priori, and the patients had no signs of systemic articular disease or amyloidosis. Most of them were elderly, but in good health.

Adult↗

PubMed1991

Interaction of pyrophosphate ion with di-, tri- and tetra-amines in aqueous solution: a potentiometric and calorimetric study.

Successive macroscopic pKa values have been determined potentiometrically for the conjugate acids of spermidine (4-azaoctane-1,8-diamine), spermine (4,9-diazadodecane-1,12-diamine) and some acylic diamines at various ionic strengths in the absence and presence of tetrasodium pyrophosphate. The stability of the amine/pyrophosphate adducts have been estimated on the basis of effects of the pyrophosphate ion on the apparent acidity constants of the amines. Stoichiometry and thermodynamics of adduct formation have been elucidated from microcalorimetric measurements.

Amines↗

PubMed1999

Purine biosynthesis de novo in bovine retina: purification and characterization of amidophosphoribosyl transferase and phosphoribosyl pyrophosphate synthetase.

The ability of bovine retina to synthesize purines de novo is shown for the first time. Amidophosphoribosyl transferase (EC 2.4.2.14), the enzyme controlling the rate of the process, and phosphoribosyl pyrophosphate synthetase (EC 2.7.6.1), the enzyme regulating the intracellular contents of phosphoribosyl pyrophosphate (PRPP), were purified and characterized. The molecular masses of the enzyme subunits are similar to those of the purified enzyme from the liver. The molecular masses of amidophosphoribosyl transferase, PRPP synthetase catalytic subunit, and two PRPP synthetase-associated proteins are 50, 34, 39, and 41 kD, respectively. The apparent Km values of the enzymes and coenzymes are similar to those of the purified enzymes from the liver. For amidophosphoribosyl transferase, the apparent Km for Gln and PRPP are 0.75 +/- 0.05 and 0.66 +/- 0.09 mM, respectively (the corresponding Vmax values are 59 +/- 3 and 136 +/- 12 nmoles PPi/min per mg protein). For PRPP synthetase, the apparent Km for ribose-5-phosphate and ATP are 37.9 +/- 0.5 and 53 +/- 7 microM, respectively (the corresponding Vmax values are 61 +/- 4 and 52 +/- 3 nmoles PRPP/min per mg protein). The sensitivity of the retinal PRPP synthetase to inhibition by ADP and AMP was significantly lower than that of the enzyme from the liver.

Amidophosphoribosyltransferase↗

PubMed1999

Importance of geranylgeranyl pyrophosphate for mesangial cell DNA synthesis.

BACKGROUND: Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are isoprenoid products of the intracellular mevalonate pathway used for prenylation of several low molecular weight G proteins, including Ras. It is likely that platelet-derived growth factor (PDGF) stimulation of mesangial cell proliferation requires prenylated, low molecular weight G proteins. The purpose of this study was to investigate the dependence of platelet-derived growth factor-stimulated mesangial cell DNA synthesis and cell membrane Ras incorporation on FPP and GGPP. METHODS: Quiescent human mesangial cells were exposed to PDGF (25 ng/ml) to stimulate DNA synthesis. Some cells were also treated with the HMG-CoA reductase inhibitor lovastatin (2.5 to 10.0 microM), which inhibits isoprenoid synthesis, in the presence or absence of exogenous FPP or GGPP. DNA synthesis was assessed by thymidine incorporation, and Western blot analysis was used to measure total cell membrane Ras. RESULTS: Stimulation of mesangial cells with PDGF did not increase total cell membrane Ras. Lovastatin reduced cell membrane Ras, and this was prevented by simultaneous exposure of mesangial cells to exogenous FPP (2.5 to 10.0 microM) or GGPP (1 to 5 microM). Lovastatin also reduced PDGF-stimulated mesangial cell DNA synthesis by 90%, and this was completely prevented by simultaneous exposure of cells to exogenous GGPP (1 microM), but not to FPP. CONCLUSIONS: The results of this study suggest that both FPP and GGPP can provide for mesangial cell membrane Ras localization and that PDGF-stimulated mesangial cell DNA synthesis requires the isoprenoid GGPP.

Blotting, Western↗

PubMed2000

Geranylgeranyl-pyrophosphate, an isoprenoid of mevalonate cascade, is a critical compound for rat primary cultured cortical neurons to protect the cell death induced by 3-hydroxy-3-methylglutaryl-CoA reductase inhibition.

We investigated the role of the intrinsic mevalonate cascade in the neuronal cell death (NCD) induced by the inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in rat primary cortical neurons cultured from the brains of 17-d-old fetal SD rats. HMG-CoA reductase inhibitors induced NCD [HMG-CoA reductase inhibitor-induced NCD (H-NCD)] in time- and dose-dependent manners. The apoptotic characteristics were revealed by the formation of the DNA ladder and by the electron microscopical observation. During the progression of H-NCD, p53 was induced followed by the expression of Bax. Although the mevalonate completely inhibited H-NCD, the cholesterol did not. Thus, we examined two major metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP) and farnesyl-pyrophosphate (FPP), using a novel liposome system for uptake into the cells. GGPP, not FPP, prohibited H-NCD with inhibition of the induction of p53 and Bax. The inhibition of HMG-CoA reductase decreased the amount of membrane-associated Rho small GTPase families, but not Ras small GTPase, and GGPP restored the blockage by HMG-CoA reductase inhibitor in the translocation or redistribution of Rho small GTPase families to membrane. These data indicated that (1) the inhibition of the intrinsic mevalonate cascade induces the apoptotic NCD with the induction of p53 followed by that of Bax, (2) the inhibition of HMG-CoA reductase concomitantly causes blockage of the translocation or redistribution of Rho small GTPase families, not Ras small GTPase, to membrane, and (3) GGPP, not FPP, is one of the essential metabolites in the mevalonate cascade for protecting neurons from H-NCD.

Animals↗

PubMed2003

A six-week study to evaluate the anti-calculus efficacy of a chewing gum containing pyrophosphate and tripolyphosphate.

OBJECTIVE: A six-week, double-blind, cross-over clinical study was conducted to compare the effect of a new chewing gum containing pyrophosphate (1%) and tripolyphosphate (1%), versus a control chewing gum on supragingival calculus deposits. METHODOLOGY: Twenty-eight adult subjects (mean age 34 +/- 8 years) who entered the study were given a full oral prophylaxis and were assigned to chew two pieces of gum, four times a day for five minutes. The gum, either a test chewing gum or placebo chewing gum, was randomly assigned and the subjects were directed to chew their assigned gum for six weeks. All participants also received a 12-week supply of a sodium fluoride (0.32%) dentifrice (Colgate). They were then scored for calculus deposits using the modified Volpe-Manhold Calculus Index (VMI) by the same two examiners. At the end of the first six weeks, the subjects received a second oral prophylaxis and used the alternate chewing gum for a second six-week period of time. The subjects were again scored for calculus deposits and the study was completed. RESULTS: The results demonstrated a mean VMI of 3.65 +/- 2.82 for the test group, and a mean of 4.24 +/- 3.25 for the placebo group. This difference was significant with paired sample t-test (p < 0.001). CONCLUSION: These results indicated that chewing gum containing pyrophosphate and tripolyphosphate reduced supragingival calculus formation by 13.9%, compared to the placebo chewing gum.

Adult↗

PubMed2003

Calcium pyrophosphate dihydrate crystal deposition disease in cervical radiculomyelopathy.

One patient had cervical spinal canal stenosis with radiculomyelopathy due to deposition of calcium pyrophosphate dihydrate within the ligamentum flavum. The MRI of cervical spine showed a calcified nodule over C5-6 level ligamentum flavum with obvious cord compression. After posterior decompressive laminectomy with removal of the calcified nodule, the symptom and sign relieved remarkedly and the pathology showed calcium pyrophosphate dihydrate deposition within the ligamentum flavum. We presented this case and reviewed the literature to acknowledge so-call "pseudogout syndrome."

Aged↗

PubMed2004

[Jaccoud arthropathy and pyrophosphate arthropathy: a rare association].

Jaccoud's arthropathy (JA) is a chronic deformity affecting hands and feet, which are voluntarily correctable by the patients. JA was usually reported in association with rheumatic fever and systemic lupus erythematosus. We describe an exceptional association between a pyrophosphate arthropathy and JA of the hands. It is a 48-year-old woman, having a 13 years history of polyarthritis involving shoulders, elbows, hips and knees, and 4 years after, a progressive unlar deviation of the fingers of the hands. Calcium pyrophosphate dihydrate crystals were identified in the synovial knee biopsy. Hands x-rays as RMI don't identify erosions and confirmed the JA.

Arthritis↗

PubMed1975

Technetium-99m-pyrophosphate kinetics and imaging in metabolic bone disease.

A study was undertaken to investigate the behavior of 99mTc-Sn-pyrophosphate complex in metabolic bone disease. Of clinical importance was the generalized increased periarticular bone accumulation of the radiopharmaceutical in osteomalacia and in combined osteomalacia and osteitis fibrosa as found in patients with chronic renal failure. The pattern in primary hyperparathyroidism was variable. There was no correlation between the initial rates of accumulation of the radiophosphate complex or its bone to soft-tissue uptake ratio at 5 hr when compared with the degree of osteomalacia and osteitis fibrosa. It is postulated that the 99mTc-Sn-pyrophosphate complex has greater affinity for immature collagen than the crystal surface.

Adenocarcinoma↗

PubMedDate not supplied

[Study of the mutagenic properties of oligonucleotides containing and internucleotide pyrophosphate bond using a mutation system based on phage M13].

Mutagenic properties of oligonucleotides with pyrophosphate internucleotide bond was studied. It was shown that the pyrophosphate bond in the oligo structure does not induce mutations but promotes a more efficient induction of marker deletions predetermined by the nucleotide sequence as compared to the native oligonucleotide. Marker deletion induction proceeds according to the repair mechanism as homozygotes dominate in the mutant generation.

Amino Acid Sequence↗

PubMed1975

Time-dependent image quality using 99mTc-pyrophosphate.

Technetium-99m-labeled pyrophosphate has proved to be a useful skeletal-imaging agent. In this study, specific areas of the skeleton were imaged at times ranging from 1/2 to 6 1/2 hr after injection of 99mTc-pyrophosphate. Count ratios between abnormal and normal bone with respect to adjacent soft tissue were obtained for selected regions of interest on computer-stored scintillation camera images. The results show that image quality improves most rapidly from 1/2 to 2 hr, but further modest gain in quality does occur on views recorded between 2 and 6 hr. All lesions detected on the later images were also observed on the early ones and the ratios of uptake between abnormal and normal bone from computer-processed scintillation camera images did not change appreciably with time after the 1/2-hr images. Our results confirm the clinical impression that overall image quality is better on views obtained at least 3 hr after injection. Further delays in imaging beyond 3-4 hr after injection probably will not result in any appreciable gain in diagnostic accuracy.

Bone Neoplasms↗

PubMed1975

Calcium pyrophosphate dihydrate deposition disease without chondrocalcinosis.

The pseudogout syndrome is usually associated with radiographic evidence of articular cartilage calcification. Eight patients who had joints containing calcium pyrophosphate dihydrate crystals were studied. Extensive radiographic evaluation was obtained in seven patients and a limited evaluation in the other. None had evidence of chondrocalcinosis. Six had distinctive radiographic abnormalities of the wrists consisting of radiocarpal joint space narrowing and sclerosis, and subchondral cystic degeneration of the carpal bones. We conclude that calcium pyrophosphate dihydrate deposition disease and pseudogout can occur without radiographic evidence of chondrocalcinosis and that the diagnosis can be suggested by characteristic radiographic abnormalities of the wrists.

Adult↗

PubMed1976

Increased localization of 99mTc-pyrophosphate in a bone island: case report.

A positive 99mTc-pyrophosphate bone scan is reported in a proven case of large compact bone island. Pyrophosphate uptake in this case is presumed to be due to either large size or growth of the bone island. A radionuclide bone scan does not always differentiate bone islands from metastatic or inflammatory sclerotic bone lesions.

Adult↗

PubMedDate not supplied

[Inorganic pyrophosphate synthesis by the mitochondria of the yeast-like fungus Endomyces magnusii coupled with the work of the respiratory chain].

The synthesis of inorganic pyrophosphate by the mitochondria of Endomyces magnusii was found to be coupled with respiration. The mitochondria of E. magnusii can utilize the energy of the phosphoanhydride bond of inorganic pyrophosphate for the synthesis of ATP. The study with inhibitors suggests the participation of inorganic pyrophosphatase and ATPase in this process.

Adenosine Diphosphate↗

PubMed1976

Chemistry of 99mTc tracers. II. In vitro conversion of tagged HEDP and pyrophosphate (bone-seekers) into gluconate (renal agent). Effects of Ca and Fe (ii) on in vivo distribution.

Sodium gluconate transforms the bone-seekers 99mTc-HEDP and 99mTc-pyrophosphate into the renal agent 99mTc-gluconate. In these in vitro processes, pyrophosphate is displaced faster than HEDP, while the HEDP reaction is accelerated by calcium ions. The in vivo distributions of these bone and kidney agents are altered by the prior local injection of calcium or iron(II). These transformation and translocation phenomena are explained in terms of the mechanistic behavior of Tc(IV) complexes.

Animals↗