Phosphate binders and management of hyperphosphataemia in end-stage renal disease.
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This study used Prevotella nigrescens to evaluate the sealing ability of Geristore, Super-EBA, and ProRoot when used as root-end filling materials. One hundred single-canal, extracted, human teeth were cleaned and shaped with Gates-Glidden burs and .04 Taper (ProFile Series 29) rotary instruments. The root-ends were resected, and a 3-mm deep root-end preparation was made with ultrasonic tips. After steam sterilization, the teeth were randomly divided into three groups of 30. Each group was root-end-filled with a different material. Five root-end cavities were left open and served as positive controls; another five root-end cavities filled with sticky wax and covered with two layers of nail polish acted as negative controls. The teeth were attached to presterilized snap-on plastic caps; the root-ends submerged into 12-ml vials of chopped meat carbohydrate broth and placed in an anaerobic chamber. Twice a week, a sterile micropipette was used to inoculate 0.1 ml of a broth culture of Prevotella nigrescens into the root canal of each tooth. Results after 47 days indicated there were no significant differences between the three root-end filling materials against penetration of Prevotella nigrescens.
The purpose of this study was to evaluate the potential of using mineral trioxide aggregate as a root canal filling material by comparing its apical sealing ability with that of laterally condensed gutta-percha with sealer and high-temperature thermoplasticized gutta-percha with sealer in extracted bovine teeth. Sixty bovine incisors with single canals were prepared in a standard manner using LightSpeed instruments, randomly divided into three groups of 20 teeth, and obturated. The sealing ability of each technique was assessed by immersion in 1% methylene blue dye for 3 days. The teeth were cleared, and the linear extent of dye penetration was measured with a stereomicroscope. Data were analyzed by the Kruskal-Wallis one-way ANOVA followed by Dunn's test. Canals filled with laterally condensed gutta-percha or thermoplasticized gutta-percha showed significantly less apical dye penetration than canals obturated with mineral trioxide aggregate (p < 0.001). There was no significant difference in leakage between the laterally condensed group and the thermoplasticized group. The results suggest that gutta-percha obturation may provide an apical seal that is superior to MTA.
The purpose of this study was to evaluate whether intracoronal delivery of an apical barrier of mineral trioxide aggregate (MTA) placed ultrasonically, non-ultrasonically, or ultrasonically with the addition of an intracanal composite resin provided a better seal against bacterial leakage. A second purpose was to determine whether intracanal composite resin or gutta-percha and sealer placed against an apical barrier of MTA provided greater resistance to root fracture. In a standardized in vitro open apex model, MTA was placed as an apical barrier at a thickness of 4 mm, with and without ultrasonic vibration. The barriers were challenged with bacteria exposure within a leakage model, and fracture resistance was assessed with increasing forces applied via an Instron machine. After 45 days, the addition of ultrasonics significantly improved the MTA seal, compared with the non-ultrasonics treatment (Kruskal Wallis nonparametric ANOVA with Dunn multiple comparison test p < 0.05). Bacterial leakage occurred in 6 (33%) of 18 in the non-ultrasonic MTA group, 2 (11%) of 18 in the ultrasonic MTA group, and 1 (6%) of 18 in the ultrasonic MTA-composite group. There were no significant differences at 90 days. A 4-mm thickness of MTA followed with an intracanal composite resin demonstrated a significantly greater resistance to root fracture than MTA followed with gutta-percha and sealer (one-way ANOVA with Newman-Keuls multiple comparison test, p < 0.01). The MTA-gutta-percha group was not significantly different than the MTA unrestored positive control.
The purpose of this study was to compare the retentive strength of zinc-phosphate cement, glass-ionomer cement, and mineral trioxide aggregate (MTA) cement in the retention of prefabricated posts. The root canals of 60 bovine incisors were prepared and obturated with warm gutta-percha. Post space was prepared, the smear layer removed, and posts were luted with zinc-phosphate cement, glass-ionomer cement, or MTA. The specimens were stored at 37 degrees C and 100% humidity for 2 weeks, and then subjected to increasing axial tensile forces by an Instron machine until bond failure occurred. Data were analyzed by a one-way ANOVA and a Tukey-Kramer multiple comparison test. The retentive strengths of zinc phosphate and glass-ionomer cements were statistically equivalent, and significantly greater than MTA (p < 0.001), which suggests that zinc phosphate or glass-ionomer cement may be superior to MTA when used as luting agents for posts in endodontically treated teeth.
The purposes of this investigation were 2-fold: to study the physical properties and sealing ability of Viscosity Enhanced Root Repair Material (VERRM); and, to compare them with Mineral Trioxide Aggregate (MTA). VERRM has a composition similar to mineral trioxide aggregate, with handling characteristics and consistency similar to commercially available materials such as IRM and Super EBA. The pH, setting times, solubility, radiopacity, dimensional change upon setting, and apical sealing ability of VERRM were evaluated and compared to that of ProRoot MTA (GMTA) and ProRoot MTA (Tooth Colored Formula) (WMTA). The results showed that VERRM had physical properties similar to WMTA. VERRM and WMTA showed significantly greater dye penetration than GMTA (p < 0.05) when used as a root-end filling material. There was no significant difference in depth of dye penetration between VERRM and WMTA. Further development of VERRM is indicated to produce a biocompatible root-end filling material with superior handling characteristics.
The secondary hyperparathyroidism that develops in rats with chronic renal insufficiency (CRI) can be totally prevented by activation of the parathyroid Ca(2+) receptor with a calcimimetic compound, when treatment is initiated before parathyroid cell hyperplasia and increased circulating parathyroid hormone levels develop. In clinical practice, however, secondary hyperparathyroidism is usually manifest by the time CRI is diagnosed. This study examined the effects of daily oral gavage or continuous subcutaneous infusion for 8 wk of the calcimimetic NPS R-568 on the progression of established mild or moderate-to-severe secondary hyperparathyroidism in rats with CRI induced by 5/6 nephrectomy. Both oral and infused NPS R-568 completely prevented further hyperplasia but did not reduce total parathyroid cell number below that present at the initiation of treatment. This prevention of cellular proliferation occurred despite increases in plasma phosphate and decreases in Ca(2+) and 1, 25-dihydroxyvitamin D levels, and supports the view that the Ca(2+) receptor is the dominant regulator of parathyroid cell hyperplasia in addition to parathyroid hormone secretion. The clinical implications of these findings suggest that controlling Ca(2+) receptor activity with calcimimetic compounds could be sufficient to manage secondary hyperparathyroidism in CRI.
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Fourteen new 4-aryl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives were synthesized and screened in vitro for their calcium antagonistic activities. The compounds were prepared by reacting 1,3-cyclo-hexanedione with appropriate aromatic aldehydes and thiourea under modified Biginelli reaction conditions. The structures of the compounds were proved by IR, 1H-NMR, mass spectroscopy and elemental analysis. The compounds synthesized exerted calcium antagonistic action on smooth musculature by inhibiting BaCl2-induced contractions of isolated rat ileum. It was found that compound 12l having 3-methoxyphenyl group at the 4th position was the most potent compound in this series (pEC50: 4.00 +/- 0.20). Rasemic compound 12l was resolved into its enantiomers by high performance liquid chromatography (HPLC) using a commercially available cellulose tris(p-methylbenzoate) chiral stationary phase, known as Chiralcel OJ. The enantiomeric ratio was validated and peak identification for each enantiomer was established according to their optical rotation sign.
Organic compounds that block calcium channel current (calcium antagonists) are important tools for the characterization of this channel. However, the practically irreversible nature of this block restricts the usefulness of this group of drugs. In this paper, we investigate the influence of light on calcium channel blockade by several organic compounds. Our results show that inhibition of calcium channel current by two dihydropyridine derivatives that contain an o-nitro moiety (nisoldipine and nifedipine) can be rapidly reversed by illumination. The energy range important to this reaction is for light wavelengths between 320 and 450 nm. Calcium channel inhibition by two other dihydropyridine derivatives (nicardipine and nitrendipine) as well as by D600, is not modulated by illumination. These results indicate that the photosensitivity of certain dihydropyridine calcium channel blockers make these compounds useful as reversible blockers of this channel.
Calcium entry blocking activities of adenosine and its potentiating drugs, dilazep, lidoflazine and dipyridamole, were studied in potassium (100 mM)-depolarized guinea pig taenia coli, and compared with nifedipine, verapamil and diltiazem. The potency ratio of calcium entry blocking effect of nifedipine, diltiazem, lidoflazine and dilazep to verapamil was 158.5, 1/1.1, 1/15.8 and 1/81.3, respectively. Dipyridamole and adenosine had negligible calcium entry blocking effects.
Barium ion, applied as BaCl2 to the cerebral surface, produces marked constriction of pial arterioles. The present data demonstrate that this constriction is inhibited by the calcium channel blockers verapamil and nimodipine. Verapamil in concentrations as low as 10)-7) M was effective in local administration. Verapamil in milligram per kilogram doses and nimodipine in microgram per kilogram doses were effective 30 min after intraperitoneal injection without producing dilation. The basis for the inhibitory action of the calcium channel blockers is not established by the data. However, in view of barium's known ability to depolarize membranes, it may be that the constriction which results is related to inward passage of ions and is facilitated by inward movements of calcium.
AIM: To develop a homogeneous high-throughput screening (HTS) assay based on scintillation proximity assay (SPA) technology for identification of novel alpha4beta2 nicotinic acetylcholine receptor (nAChR) modulators. METHODS: Membrane preparation of HEK293 cells expressing alpha4beta2 nAChR, [(3)H]cytisine and wheat germ agglutinin (WGA)-coupled microbeads were used to develop an HTS assay based on SPA technology. This method was validated against a conventional filter binding approach and applied to large-scale screening of a library containing 32 000 synthetic compounds. Intracellular calcium measurement was carried out to verify the bioactivities of the hits found by the SPA assay. RESULTS: IC(50) values of 2 reference compounds (epibatidine and RJR 2403) determined by SPA and filter binding methods were comparable and consistent with those reported elsewhere. A total of 54 compounds, showing more than 60% competitive inhibition on [(3)H]cytisine binding to alpha4beta2 nAChR, were identified initially following an HTS campaign. Secondary screening confirmed that 17 compounds with novel chemical structures possessed relatively high binding affinity to alpha4beta2 nAChR (K(i)<2 micromol/L). Eight compounds displayed antagonistic effects with >50% inhibition on ABT-594-induced calcium mobilization while none showed any agonist activity. CONCLUSIONS: This homogeneous binding assay is a highly efficient, amenable to automation and robust tool to screen potential alpha4beta2 nAChR modulators in an HTS setting. Its application may be expanded to other membrane receptors and ion channels.
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This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values > 400 pg mL(-1), calcium levels < or = 10.5 mg dL(-1) and calcium x phosphorus product values < or = 70 mg2 dL(-2) were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5-1.5 microg) were based on the severity of secondary HPT. The dose was increased every two weeks by 0.25 microg until there was at least a 30% decrease in PTH from baseline, or Ca > 11.0 mg dL(-1), or Ca x P > 75 mg2 dL(-2). Overall, 11/21 (52%) patients in the calcitriol group had two consecutive > or = 30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L(-1) in the calcitriol group and increased from 547 to 669 IU L(-1) in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 microg L(-1) in the calcitriol group and increased from 105.3 to 148.5 microg L(-1) in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium x phosphorus (Ca x P > 75 mg2 dL(-2)) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus > 6.5 mg dL(-1) occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels > 10.5 mg dL(-1) were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P<0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that i.v. calcitriol, at initial doses of 0.5-1.5 microg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca x P product.
The effect of diazoxide, verapamil and compound D600 on calcium and isoproterenol dose-response relationships was investigated in isolated rabbit atrial preparations. All three agents shifted calcium dose-force relationships parallel and to the right. D600 acted as a competitive antagonist of calcium, as a plot of log (x - 1) vs. -log B resulted in a straight line with a slope of approximately -1.0. Diazoxide, verapamil and D600 also antagonized isoproterenol but in a non-competitive manner. A reduction of calcium in the bathing fluid produced a qualitatively similar non-competitive antagonism of isoproterenol and markedly potentiated diazoxide antagonism of isoproterenol. We conclude that: (1) diazoxide has calcium antagonistic properties similar to the "calcium antagonists" verapamil and D600; (2) these agents act as competitive antagonists of calcium through a specific site that is beyond the beta-adrenergic receptor and in the series of events between the beta-adrenergic receptors and inotropic response in myocardial tissue.
N1E-115 mouse neuroblastoma cells were injected with the calcium indicator dye arsenazo III. Optical absorbance changes during voltage-clamp depolarization were used to examine the properties of the two calcium currents present in these cells. The rapidly inactivating calcium current (Moolenar and Spector, 1979b, Journal of Physiology, 292:307-323) inactivates by a voltage-dependent mechanism. The slowly inactivating calcium current is dominant in raising intracellular calcium during depolarizations to greater than -20 mV. Lowering the extracellular calcium concentration affects the two calcium currents unequally, with the slowly inactivating current being reduced more. Intracellular calcium falls very slowly (tau greater than 1 min) after a depolarization. The rapidly inactivating calcium current is responsible for a calcium action potential under physiological conditions. In contrast, it is unlikely that the slowly inactivating calcium current has an important electrical role. Rather, its function may be to add a further increment of calcium influx over and above the calcium influx through the rapidly inactivating calcium channels.
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