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Comparative intraoral tolerance of sodium hexametaphosphate and pyrophosphate antitartar dentifrices.

A randomized, controlled clinical trial was conducted to assess the relative acute oral tolerance of a novel, dual-phase, tartar control dentifrice containing 7.0% sodium hexametaphosphate (5% hexametaphosphate anion). In this 4-day study, 159 healthy adult volunteers were randomly assigned to the experimental sodium hexametaphosphate dentifrice or a marketed, single-phase, antitartar dentifrice control containing 5.0% ionic pyrophosphate. A detailed oral soft tissue examination and interview were conducted each day by blinded evaluators to elicit clinical signs and symptoms associated with ad libitum use of the assigned dentifrice. A total of 24 subjects (15% of the study population) had new symptoms/signs after baseline. By treatment, 9% of subjects in the sodium hexametaphosphate group had new findings, compared to 21% of subjects in the pyrophosphate group, and these groups differed statistically (p < 0.03, two-sided) with respect to occurrence. In addition, onset, severity, duration and clinical presentation were generally milder in the sodium hexametaphosphate group compared to the pyrophosphate control. Only one subject (in the pyrophosphate group) discontinued treatment early due to oral intolerance. In this study, the 7.0% sodium hexametaphosphate dentifrice was well-tolerated, with significantly fewer symptoms and superior overall tolerance compared to the marketed antitartar dentifrice control.

Adult↗

Kinetics of 99mTc-labeled pyrophosphate and polyphosphate in man.

Thekinetic of 99mTc-labeled pyrophosphate were compared with those of polyphosphate in ten patients in a combined study. Both agents cleared from the blood in a biexpoential fashion. The clearance half-time of Exponent I was the same for both and was shorter than the clearance half-time of Exponent ii. Urinary excretion of both agents was the same during the first hour but during the next 3 hr Tc-pyrophosphate cleared at a slightly more rapid rate, resulting in lower blood background radioactivity. Both agents were bound loosely to plasma proteins, mainly to globulin fractions. The sensitivity of lesion detection was similar for both. Excellent bone images were obtained with both agents. The images with Tc-pyrophosphatewere consistently superior owing to the low blood background and they took less time to accumulate an identical number of counts from identical regions. With the amount of 99mTc-complex used, no hyocalcemia or tetany was noted, nor was there any significant effect on 1-hr serum levels of inorganic phosphours and alkaline phosphatase. Four hours after injection, 9.5% of the dose of Tc-pyrophosphate was circulating in blood, 31.7% was excreted in urine, and the remaining 58.8% was taken up by bone and other tissues. The corresponding values with Tc-polyphosphate were 12.5% in blood, 29.0% in urine, and 58.5% in bone and other tissues. Among the soft tissues, the genitourinary system is most consistently visualized. It is concluded that both Tc-pyroposphate and Tc-polyphosphate are excellent skeletal-imaging agents and that Tc-pyrophosphate appears slightly superior to Tc-polyphosphate.

Blood Proteins↗

[Bone scintigraphy with 99mTc-pyrophosphate: pharmokinetics of the substance and clinical experiences with the scintigraphy].

Kinetics and clinical studies of bone scintiscanning with 99mTc-pyrophosphate in 92 patients with certified diagnosis allowed the following conclusions: 1. After i.v. injection 99mTc-pyrophosphate is distributed in 3 compartments, from which it is cleared with biological half-lives of 32.7 minutes, 5.1 hours and 22.54 hours respectively. The relative size of these compartments is 1 : 3 : 6. After application of the substance, an initially high renal excretion with a consecutive exponential drop can be observed. The optimal period for scintigraphic studies seems therefore to be from 3-6 hrs, as at this time there is still an adequate activity in bone structures, while the low background activity yields a good contrast on scintiscans. 2. The clinical results of bone scintigraphy with 99mTc-pyrophosphate with 88.6% correct diagnoses can be considered as "very good". This feature can partly be attributed to an improved correlation of radiographic and scintigraphic images by the use of a specially designed, combined radiographic-photoscanning detector system. 3. Preliminary results concerning the quantitative uptake of 99mTc-pyrophosphate in fractures of the extremities suggest, that the quantitative analyses of the registered data can provide valuable prognostic information in traumatic, inflammatory and neoplastic bone lesions.

Bone Diseases↗

Calcium pyrophosphate. Histological characterization of crystals in pseudogout.

Deposits taken from an acetabulum and the head of a femur and known to contain crystals of calcium pyrophosphate were examined by selected histological methods for calcium after the application of a variety of solvents. Treatment with 10% ferric chloride removed all calcium salts tested, except a birefringent crystalline component in the pyrophosphate deposits. This corresponds to the previous optical and morphological descriptions of calcium pyrophosphate as found in synovial fluids. Calcium pyrophosphate stains consistently only by the fluorescent morin method.

Acetabulum↗

Fluoride uptake from NaF/pyrophosphate anticalculus dentifrices in vitro: effect of pyrophosphate dose.

Fluoride uptake from anticalculus dentifrices containing combinations of sodium fluoride and variable doses of soluble pyrophosphate has been evaluated in an in vitro fluoride uptake model. Artificial carious lesions were treated for 30 minutes in 25% w/w saliva slurries of dentifrices. Fluoride uptake into the partially demineralized enamel was assessed by microdrill biopsy. Results show equivalent fluoride uptake for dentifrices containing 0.243% sodium fluoride in combination with 0, 4.0 and 5.0% soluble pyrophosphate. These results, coupled with analytical measures of available fluoride, suggest no negative effects of pyrophosphate on fluoride availability or access to artificial carious lesions for soluble pyrophosphate concentrations up to 5.0% in a conventional (1,100 ppm fluoride) sodium fluoride dentifrice system.

Dentifrices↗

[Demonstration of a pyrophosphate-fructose 6-phosphate 1-phosphotransferase in the latex from Hevea brasiliensis].

A pyrophosphate: fructose-6-phosphate 1-phosphotransferase activity (EC 2.7.1.90) has been characterized in cytosol from Hevea brasiliensis latex. It is Mg+ dependent enzyme, and the cation has an optimal effect between 2.5 to 3 mM for a concentration of 1 mM of pyrophosphate and 10 mM of fructose-6-phosphate. It is activated by catalytic content of fructose-2,6-diphosphate. Its potential activity is higher than 40% of that of ATP dependent phosphofructokinase (EC 2.7.1.11). Its optimum pH is between 7.5-7.6; then, the enzyme affinity is 0.3 mM for pyrophosphate and 3.5 mM for fructose-6-phosphate. It is suggested that the transferase plays a role in the pyrophosphate metabolism and the increasing of the energetic efficiency of glycolysis and so takes a significant part in the biochemical mechanisms involved in the latex yield.

Cytosol↗

Incorporation of N-acetyl-D-glucosamine from UDP-N-acetyl-D-glucosamine by isolated membranes of Bacillus subtilis. Identification of undecaprenyl poly(N-acetylglucosaminyl pyrophosphate).

Membrane isolated from Bacillus subtilis strain 168 incorporated GlcNAc from UDP-GlcNAc directly onto undecaprenyl phosphate via transphosphorylation and subsequent transglucosylations. Chain lengths of 6, 4, and 1 units of GlcNAc were found. Approximately 80% of the isotope incorporated was extracted into chloroform:methanol (2:1 v/v), and could be distinguished from the undecaprenyl disaccharide cell wall intermediate by a different elution pattern on DEAE-cellulose (acetate form). The GlcNAc-lipid(s) were eluted from a similar column in chloroform:methanol:water (10:10:3, v/v) with 6 mM NH4COOH indicating a pyrophosphate linkage between the lipid and the GlcNAc. The GlcNAc-lipid(s) were not degraded by conditions which completely deacylated [32P]glyceryl phospholipids, but were rapidly hydrolyzed by mild acid treatment (0.005 N HCl, 90 degrees) with the release of oligosaccharide phosphate (typical of sugars linked to undecaprenyl pyrophosphate). Catalytic hydrogenation of the GlcNAc-lipid(s) resulted in the release of water-soluble sugar phosphate. Under these same conditions, undecaprenyl pyrophosphate and undecaprenyl disaccharide cell wall intermediate were similarly effected while [32P]glyceryl phospholipids remained intact. The formation of GlcNAc-lipid(s) in vitro was inhibited if membranes were prepared from cells previously treated with bacitracin. Thus, the GlcNAc-lipid(s) has the properties of undecaprenyl poly(N-acetylglucosaminyl pyrophosphate) and may represent a new synthetic role of the polyisoprenyl lipid in B. subtilis.

Bacillus subtilis↗

Urinary pyrophosphate in normal subjects and in stone formers.

The urinary excretion of inorganic pyrophosphate was determined in nine normal subjects and also in eight patients with recurrent calcium-containing renal stones during varied levels of phosphate intake. The excretion of pyrophosphate and orthophosphate is virtually the same in the two groups at all levels of phosphate intake. It appears unlikely that a consistently reduced urinary excretion of pyrophosphate is a factor in the formation of urinary calculi. Pyrophosphate excretion rose and calcium excretion fell with increasing phosphate intake; this might be expected to have a beneficial effect in patients with recurrent calcium stones.

Adult↗

Accumulation of technetium-99m stannous pyrophosphate in contused myocardium.

The uptake of technetium-99m stannous pyrophosphate in contused myocardium was measured as a function of time from the insult. The free wall of the dog's left ventricle was surgically exposed and struck with a spring-loaded paddle. Pyrophosphate was injected intravenously from 1 1/2 to 47 1/2 hr after the injury. After 1/2 hr of incubation the hearts were removed and the Tc-99m content of contused and noncontused myocardium was measured. Pyrophosphate was concentrated in contused myocardium at all of the time periods tested. Contused-to-normal ratios for pyrophosphate uptake ranged from 8.1 (8 hr) to 41.9 (48 hr).

Animals↗

Accumulation of pyrophosphate correlates with the increased level of nucleoside triphosphates in Escherichia coli.

We measured the concentration of nucleoside triphosphates and inorganic pyrophosphate in Escherichia coli in conditions where nucleotide synthesis or nucleic acid synthesis was inhibited. The inhibitors that brought about an accumulation of some of the four ribonucleoside triphosphates also increased the pyrophosphate level. In a pyrimidine auxotrophic strain uracil starvation led to simultaneous accumulation of ATP and pyrophosphate, and they both rapidly returned to normal level when starvation was relieved. These results indicate the possible involvement of pyrophosphate in the reactions leading to the accumulation of nucleoside triphosphates.

Adenosine Triphosphate↗

Enzymatic activities associated with avian and murine retroviral DNA polymerases. Catalysis of and active site involvement in pyrophosphate exchange and pyrophosphorolysis reactions.

Reverse transcriptase isolated from avian myeloblastosis virus (AMV) and Rauscher murine leukemia virus (RLV) were examined for their ability to catalyze polymerization, ribonuclease H, pyrophosphate exchange, and pyrophosphorolysis reactions. A detailed characterization and a study of requirements for the expression of pyrophosphate exchange and pyrophosphorolysis reactions indicated that a variety of RNA and DNA template-primers supported these catalytic reactions. Furthermore, hydrogen bonding of template to primer was essential, although RNA:RNA template-primers, e.g. poly(rA) . (rU)9 or 70 S RNA . tRNA complex, were not utilized for these reactions. AMV enzyme required Mg2+, and RLV enzyme Mn2+, as the preferred divalent metal ion for the expression of these activities. Response of various catalytic reactions to site-specific inhibitors revealed that polymerization and pyrophosphate exchange reactions were susceptible to reagents that affected either the substrate or the template binding site, intrinsic zinc, or sulfhydryl groups. RNase H and pyrophosphorolysis activities, on the other hand, exhibited susceptibility only to the template site-specific reagent. We, therefore, conclude that RNase H and pyrophosphorolysis reactions are catalyzed through the template binding site while polymerization and pyrophosphate exchange reactions require additional participation of the substrate binding site, as well as that of intrinsic zinc and the presence of reactive sulfhydryl groups.

Avian Leukosis Virus↗

[The technetium-99-m-pyrophosphate scintigram in the assessment of the size of acute myocardial infarction: comparison with CK-(MB) curves mortality (author's transl)].

While the technetium-99m-pyrophosphate scintigram enables diagnostic proof of acute myocardial infarction, its use in the evaluation of the extent of infarction has not been clearly established. This study, in 30 patients with acute myocardial infarction was, thus, undertaken to assess the relationship between the findings of the technetium-99m-pyrophosphate scintigram, with respect to infarct area and uptake pattern, the infarct size, as determined from the total CK an CK-MB curves, and the mortality. The scintigraphically determined infarct areas ranged between 1.7 and 29.3 cm2; the 20.2 plus or minus 6.0 cm2 average for anterior wall infarction (n=18, range 7.4 to 29.3 cm2) was significantly greater (p smaller than 0.005) than the 8.3 plus or minus 5.3 cm2 average for inferior infarction (n=12, range 1.7 to 15.8 cm2). Correlation coefficients between the scintigraphically and enzymatically determined infarct sizes for the entire patient population ranged from 0.71 to 0.80. Anterior infarctions correlated more closely (0.66 to 0.84) than inferior infarctions (0.46 to 0.66). The technetium-99m-pyrophosphate uptake pattern was focal in 20 patients and ring-shaped (doughnut) in ten. Infarcts with focal uptake patterns were significantly smaller than those displaying a doughnut pattern (12.2 plus or minus 6.4 vs. 24 plus or minus 4.0 cm2, p smaller than 0.005). The infarct weight calculated from the CK-MC curve with application of individually determined disappearance rate for those infarcts displaying a focal uptake pattern was 34 plus or minus 29 grams while that associated with a doughnut uptake pattern was significantly greater at 86 plus or minus 25 grams (p smaller than 0.005). During the 18 -month observation period there were six deaths; the average scintigraphic infarct area of 22.8 plus or minus 3.6 cm2 in those who died was significantly greater (p smaller than 0.005) than that of the 13.8 plus or minus 8.2 cm2 of the survivors. Of the non-survivors, five had a doughnut uptake pattern and one displayed focal uptake. In the 24 survivors, a focal uptake pattern was found in 19 and a doughnut pattern in five. Conversely, 19 of the 20 patients with a focal uptake pattern survived while only five of the ten patients with a doughnut pattern were alive after 18 months. Thus, comparison with the enzymatically determined infarct weight as well as the mortality indicate that the technetium-99m-pyrophosphate scintigram yields clinically relevant data with regard to infarct size. Since no patient with an infarct area of less than 17 cm2 died within the 18-month observation period, designation of scintigraphically determined infarct size as small (smaller than 17 cm2) and large (larger than 17 cm2) was enabled. The corresponding cut-off point between large and small infarctions as determined enzymatically has been designated at 65 grams. Accordingly, agreement was found in 70% (14 of 20 patients) with scintigraphically small infarcts and in 80% (8 of 10 patients) with scintigraphically large infarcts...

Acute Disease↗

Enzymic measurement of urinary pyrophosphate with a centrifugal analyzer.

We describe a simple, rapid, and fully automated technique for measuring urinary pyrophosphates with a centrifugal analyzer (the ENI GEMSAEC). This technique depends on the enzymic magnesium-dependent reaction with UDPG pyrophosphorylase (UTP: alpha-D-glucose-1-phosphate uridylyl transferase, EC 2.7.7.9) and spectrophotometry of the NADPH formed in a combined system of phosphorylation and reduction. Many samples of urine can be analyzed quickly without pretreatment, with high sensitivity (1.3 mA/mumol of substrate) and good reproducibility. The mean within-run coefficient of variation for a 50 mumol/L pyrophosphate solution was 1.4%. We determined the optimum enzyme and magnesium concentrations necessary for use in a 4-min reaction. Because there is no inhibitory effect of chloride and phosphate ions, pyrophosphate can be measured directly in urine, without prior extraction. With this technique, the mean value (and SD) for urinary pyrophosphate excretion by 30 healthy subjects was 39.3 (SD 17.2) mumol/24 h.

Autoanalysis↗

[Synthesis of pyrophosphate by rat liver cytoplasmic and mitochondrial pyrophosphatases].

The kinetics of pyrophosphate synthesis catalyzed by rat liver cytosolic and mitochondrial pyrophosphatase in the presence of Mg2+ as cofactor has been studied. According to the kinetic model, this reaction proceeds through two parallel pathways: pathway I utilizing two magnesium phosphate molecules and pathway II utilizing both magnesium phosphate and free phosphate. Pyrophosphate formation is greatly facilitated in the active sites of the enzymes ([E.PPi]/[E.2Pi] = 0.11-0.24). Both enzymes are characterized by high efficiency in pyrophosphate synthesis in solution: the catalytic constants for the cytosolic and mitochondrial pyrophosphatases are 14 and 9.3 s-1, respectively (9 and 16% relative to those for PPi hydrolysis). The results obtained demonstrate that enzyme-catalyzed synthesis of pyrophosphate can proceed at a high rate in the absence of any external energy input, such as that provided by the proton-motive force in membrane systems.

Animals↗

Pyrophosphate arthropathy in two Swedish families.

A clinical and radiographic survey of 110 members of 2 families with hereditary pyrophosphate arthropathy was performed. The mode of inheritance was autosomal, dominant with a variable penetrance. Twenty-two percent of the family members had joint involvement related to pyrophosphate arthropathy, 47% of those over 50 years of age had experienced acute attacks of arthritis and/or had joint calcifications. The majority of individuals with both arthritis and joint calcifications suffered from chronic pain that resulted in early retirement. A high frequency of back pain was observed, but no ankylosis or deformity. Surgery was performed for parathyroid hyperplasia on the propositus in 1 family, and several members of her family suffered from symptoms that suggested a disturbance of calcium phosphate metabolism. There were several differences between our patients and 50 cases of sporadic pyrophosphate arthropathy from the same area of Sweden. Familial cases had an earlier onset, a greater number of involved joints, and peripheral joint involvement more often. Back pain was more frequent, and calcifications of intervertebral discs were found only in the hereditary cases.

Adult↗

Preparation and characterization of RF magnetron sputtered calcium pyrophosphate coatings.

CaP ceramic has been widely used as coating on metals in orthopedics and oral dentistry. Variations in CaP composition can lead to different dissolution/precipitation behavior and may also affect the bone response. In the present study calcium pyrophosphate and hydroxylapatite coatings were successfully prepared by RF magnetron sputtering deposition. The phase composition, morphological properties, and the dissolution in SBF were characterized by using XRD, FTIR, EDS, SEM, and spectrophotometry. The results showed that all the sputtered coatings were amorphous and changed into a crystal structure after IR-radiation. The temperature for the crystallization of the amorphous coatings is lower for the hydroxylapatite coating (550 degrees C), compared to the calcium pyrophosphate coating (650 degrees C). All sputtered amorphous coatings were instable in SBF and dissolved partially within 4 wks of incubation. The heat-treated coatings appeared to be stable after incubation. These results showed that magnetron sputtering of calcium pyrophosphate coating is a promising method for forming a biocompatible ceramic coating.

Calcium Pyrophosphate↗

Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model.

111In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r = 0.88) but was poorly correlated with labelled antibody uptake (r = 0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin.

Animals↗

The effect of parathyroid hormone on technetium-99m pyrophosphate distribution in rats.

Sprague-Dawley rats were treated with varying quantities of parathyroid hormone for 1--3 days, then sacrificed at periods ranging from 1--6 h after administration of 99mTc-pyrophosphate. Very little increase in bone accumulation of tracer occurred with this treatment. A small, but obvious decrease occurred in the blood levels of 99mTc-pyrophosphate and a smaller and less consistent decrease was affected in the muscle levels of the radiopharmaceutical. The overall result was an improvement in the bone/blood and bone/muscle ratios. It is suggested that the basis of the "supernormal" bone scan of hyperparathyroidism is achieved by this mechanism and that the increased bone uptake of other ions in response to parathyroid hormone is not shared by 99mTc-pyrophosphate.

Animals↗