Bond strength and solubility of a novel polydimethylsiloxane-gutta-percha calcium silicate-containing root canal sealer.

BACKGROUND: Endodontic sealers are essential for sealing gutta-percha to the dentin walls. They help to ensure that the canal remains free of microorganisms which might lead to infection. In order to perform their intended function, the sealers should properly adhere to the dentin walls and remain insoluble when set in the canal. OBJECTIVES: The purpose of this study was to evaluate the bond strength and solubility of a novel polydimethylsiloxane-gutta-percha calcium silicate-containing root canal sealer (GuttaFlow® bioseal) and compare it with the zinc oxide and eugenol sealer (Zical®). MATERIAL AND METHODS: The endodontic sealers used in this study were GuttaFlow bioseal and Zical. The bond strength was assessed using push-out bond strength test in 3 root segments: coronal, middle and apical. The solubility was tested according to the American National Standards Institute / American Dental Association (ANSI/ADA) specification No. 57 at 3 different time intervals: 1, 7 and 14 days. RESULTS: The push-out bond strength in all root segments was significantly higher in Zical compared to GuttaFlow bioseal. The solubility was significantly higher on day 1 and 7 in Zical compared to GuttaFlow bioseal, and on day 14, the difference between them was not significant. CONCLUSIONS: Within the limitations of this study, the endodontic sealer GuttaFlow bioseal showed low bond strength values compared to Zical. The solubility of the set GuttaFlow bioseal and Zical were both within the recommended ANSI/ADA levels.

Strontium released bi-lineage scaffolds with immunomodulatory properties induce a pro-regenerative environment for osteochondral regeneration.

The different lineage-specific biological properties of articular cartilage and subchondral bone present a great challenge in the construction of bi-lineage scaffolds for simultaneous osteochondral regeneration. To overcome this challenge, strontium incorporated calcium silicate (Sr-CS) ceramic was prepared for bi-lineage formation of scaffolds in this study. The positive result of Sr-CS in the regeneration of osteochondral defects was first proven by its improved effect on the osteogenesis and chondrogenesis induction of mesenchymal stem cells (MSCs). After that, scaffold-mediated macrophage polarization between classically activated inflammatory macrophages (termed M1Ф) and alternatively activated inflammatory macrophages (termed M2Ф) was assayed to investigate whether the incorporation of Sr into calcium silicate could alter host-to-scaffold immune response. Furthermore, the interactions between Sr-CS pretreated macrophages and MSCs differentiation were performed to prove the enhancement effect of suppressed inflammatory response on osteogenesis and chondrogenesis. In vivo transplantation showed that the Sr-CS scaffolds distinctly improved the regeneration of cartilage and subchondral bone, as compared to the calcium silicate scaffolds. On the one hand, the mechanism attributes to enhancement of strontium on the osteogenic and chondrogenic differentiation of MSCs. On the other hand, the reason can partially be attributed to suppressed synovial inflammatory response, which has improved effects on enhancement of osteogenesis and chondrogenesis. These findings suggest that monophasic Sr-CS scaffolds with a bi-lineage conducive property and an inflammatory response regulatory property represents a viable strategy for simultaneous regeneration of osteochondral defects.

Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635).

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain-of-function mutations of the calcium-sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1. Five adults with ADH1 due to four distinct CAR mutations received escalating doses of the calcilytic compound NPSP795 (SHP635) on 3 consecutive days. Pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed. Parallel in vitro testing with subject CaR mutations assessed the effects of NPSP795 on cytoplasmic calcium concentrations (Ca2+i ), and ERK and p38MAPK phosphorylation. These effects were correlated with clinical responses to administration of NPSP795. NPSP795 increased plasma PTH levels in a concentration-dependent manner up to 129% above baseline (p = 0.013) at the highest exposure levels. Fractional excretion of calcium (FECa) trended down but not significantly so. Blood ionized calcium levels remained stable during NPSP795 infusion despite fasting, no calcitriol supplementation, and little calcium supplementation. NPSP795 was generally safe and well-tolerated. There was significant variability in response clinically across genotypes. In vitro, all mutant CaRs were half-maximally activated (EC50 ) at lower concentrations of extracellular calcium (Ca2+o ) compared to wild-type (WT) CaR; NPSP795 exposure increased the EC50 for all CaR activity readouts. However, the in vitro responses to NPSP795 did not correlate with any clinical parameters. NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose-dependent manner, and thus, serves as proof-of-concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype or the response to calcilytics, suggesting that other parameters impact the response to the drug. © 2019 American Society for Bone and Mineral Research.

Addition of phosphates and chlorhexidine to resin-modified MTA materials.

To evaluate the properties of experimental mineral trioxide aggregate (MTA) resin-modified materials for root-end filling procedures, varying their compositions regarding the addition of hydroxiapatite (HA) or dicalcium phosphate dihydrate, with or without chlorhexidine digluconate. White MTA (Angelus, Londrina, Brazil) was used as a reference material. Degree of conversion (DC) was evaluated by Fourier transformed infrared (FTIr) spectroscopy (n = 5). Flowability (n = 3) and radiopacity (n = 3) were evaluated following ISO 6876:2001 methods. For splitting tensile strength analysis, cylindrical samples (n = 10) were subjected to compressive load using a universal testing machine (Instron Corporation, Norwood, MA). Water sorption and solubility tests were performed according to ISO 4049:2009 methods. Calcium ion release and pH analysis (n = 10) were evaluated using a pH meter (Orion, Watsonville, CA). Cytotoxicity (n = 8) of materials extracts was evaluated as cell viability percentage. Statistical analysis was performed using Kolmogorov-Smirnov for normal distribution and data was subjected to one-way ANOVA and Tukey test (α = 0.05). Addition of chlorhexidine digluconate reduced DC mean values for experimental materials (<50%). White MTA demonstrated lower flowability (5.3 mm) and higher radiopacity (9.8 mm Al), splitting tensile strength (9.1 MPa), solubility (8.2 µg/mm3 ), calcium ion release (~26.5 ppm), cytotoxicity (55.2%), and pH mean values (10.8), when compared to experimental materials. All groups demonstrated a decrease in calcium release (<85%) and pH (<13%). Formulation containing HA demonstrated similar pH values after 28 days when compared to white MTA. Evaluated experimental resin-modified MTA based materials without chlorhexidine digluconate showed satisfactory results for all physico-chemical properties tested and cytotoxicity. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2195-2201, 2019.

Effect of ultrasonic activation on dentinal tubule penetration of calcium silicate-based cements.

This study investigated the dentinal tubule penetration of mineral trioxide aggregate (MTA), NeoMTA Plus and Biodentine placed by either manual condensation or ultrasonic activation in simulated open apex model. Standardized divergent open apex models were created using palatal roots of 60 human maxillary molars and divided into six groups according to the used cements and activation methods (n = 10): MTA-manual condensation, MTA-ultrasonic activation, NeoMTA Plus-manual condensation, NeoMTA Plus-ultrasonic activation, Biodentine-manual condensation, Biodentine-ultrasonic activation. For the measurement of penetration, the cements were mixed with 0.1% Rhodamin B and 6-mm apical portions of each root canal were obturated in an orthograde direction. The roots were embedded into acrylic blocks, and 1-mm-thick sections were obtained at 3 mm from the apex. Specimens were mounted onto glass slides and scanned under a confocal laser scanning microscope (CLSM) and stereomicroscope. Dentinal tubule penetration areas, depth and percentage were measured using LSM and ImageJ software. The data were analyzed using two-way analysis of variance (anova) with Bonferroni correction (α = 0.05). No correlation was found between stereomicroscope and CLSM analyses (p > .05). CLSM analysis showed no significant differences between MTA, NeoMTA Plus, and Biodentine groups when manual condensation was used (p > .05). Ultrasonic activation did not increase the tubular penetration of MTA, NeoMTA Plus or Biodentine as compared to manual condensation of each material (p > .05). MTA, NeoMTA Plus and Biodentine showed similar tubular penetration when manual condensation was used. Ultrasonic activation of these cements had no effect on tubular penetration of each material as compared to the manual condensation counterparts.

Self-production of oxygen system CaO2 /MnO2 @PDA-MB for the photodynamic therapy research and switch-control tumor cell imaging.

Photodynamic therapy (PDT) holds promise in biochemical study and tumor treatment. A novel multifunctional nanosystem CaO2 /MnO2 @polydopamine (PDA)-methylene blue (MB) nanosheet (CMP-MB) was designed. CaO2 nanoparticles were encapsulated by MnO2 nanosheet, and then PDA was coated on the surface of CaO2 /MnO2 nanosheets, which could adsorb photosensitizer MB through hydrophobic interaction or π-π stacking. In this nanosystem, CaO2 /MnO2 had the ability of self-production of oxygen, which solved the problem of tumor hypoxia largely. Moreover, it is worth mentioning that the fluorescence of MB was suppressed by MnO2 , while its emission was triggered in the simulated tumor microenvironment. Therefore, CMP-MB nanosheet could be used to switch-control cell imaging potentially. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide testing and Live/Dead assay confirmed CMP-MB nanosheet had fewer side effects without illumination while it destroyed Hela cell with the illumination of light. Vitro cell experiment demonstrated CMP-MB nanosheet could achieve tumor microenvironment responsive imaging and inhibit tumor cell growth under illumination effectively. Therefore, the system has great potential for PDT application and switch-control tumor cell imaging. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2544-2552, 2018.

Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes.

Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH2-MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function. NH2-MSNs, SUCC-MSNs and PEG-MSNs were well tolerated, 50 µg/ml PEI-MSNs induced 100% lethality 48 hours post fertilization (hpf). Dechoroniated embryos were more sensitive and 10 µg/ml PEI-MSNs reduced viability to 5% at 96hpf. Sensitivity to PEG- and SUCC-, but not NH2-MSNs, was also enhanced. Typically cardiovascular toxicity was evident prior to lethality. Confocal microscopy revealed that PEI-MSNs penetrated into the embryos whereas PEG-, NH2- and SUCC-MSNs remained aggregated on the skin surface. Direct exposure of inner organs by microinjecting NH2-MSNs and PEI-MSNs demonstrated that the particles displayed similar toxicity indicating that functionalization affects the toxicity profile by influencing penetrance through biological barriers. The data emphasize the need for careful analyses of toxicity mechanisms in relevant models and constitute an important knowledge step towards the development of safer and sustainable nanotherapies.

Evaluation of calcium (Ca2+) and hydroxide (OH-) ion diffusion rates of indirect pulp capping materials.

INTRODUCTION: The aim of this study was to evaluate and compare the calcium (Ca2+) and hydroxide (OH-) ion release of 4 artificially produced pulp capping materials (MTA, Biodentin, TheraCal LC, Calsimol) used for indirect pulp capping treatment. METHODS: In total, 70 freshly extracted human third molar teeth were used for the study. Cavities of extracted teeth were prepared by round burs. The remaining dentin thickness (1 ± 0.3 mm) tissue was measured by a micrometer and cone beam computerized tomography. Indirect pulp capping was performed in the cavities using Calcimol, MTA, TheraCal LC and Biodentin. The leached Ca2+ were measured using optical emission spectrometry and the release of OH- ions using a pH meter. The measurements were performed after 24 hours, 7 days and 28 days in saline solution. Statistical analysis was performed using 1-way and 2-way analysis of variance (ANOVA) tests (p<0.05). RESULTS: Ca2+ ions were detected in treated saline solution during the experimental period for all materials. All the measurements of Biodentin and Theracal LC levels for Ca2+ ions were higher than those of the other materials (p<0.05). For all materials, Ca2+-ion release increased during the first 7 days followed by a linear decrease during the subsequent study periods. The Biodentine group showed the highest OH- ion rates compared to the other materials in the 24-hour examination period, while the scores gradually decreased during the subsequent measurement periods (p<0.05). CONCLUSIONS: Tricalcium silicate materials such as Biodentine and TheraCal LC used in this study may be preferable for indirect pulp capping because of their stimulation of hard tissue formation and ion-releasing ability.

An Unusual Complication With the Administration of a Volatile Anesthetic Agent for Status Asthmaticus in the Pediatric Intensive Care Unit: Case Report and Review of the Literature.

In severe cases of status asthmaticus, when conventional therapies fail, volatile anesthetic agents remain a therapeutic option. When delivered outside of the operating room setting, specialized delivery techniques are needed to ensure the safe and effective use of volatile anesthetic agents. We present a 16-year-old adolescent with status asthmaticus who required the therapeutic administration of the volatile anesthetic agent, sevoflurane, in the pediatric intensive care unit (PICU). Although initially effective in reducing bronchospasm, progressive hypercarbia developed due to defective functioning of the carbon dioxide absorber of the anesthesia machine. This failure occurred as the soda lime compartment filled with water accumulated from circuit humidification and continuous albuterol therapy. The role of volatile anesthetic agents in the treatment of status asthmaticus in the PICU is discussed, options for delivery outside of the operating room presented, and potential problems with delivery reviewed.

Effect of different mixing methods on the bacterial microleakage of calcium-enriched mixture cement.

BACKGROUND: Calcium-enriched mixture (CEM) cement is used in the field of endodontics. It is similar to mineral trioxide aggregate in its main ingredients. The present study investigated the effect of different mixing methods on the bacterial microleakage of CEM cement. METHODS: A total of 55 human single-rooted human permanent teeth were decoronated so that 14-mm-long samples were obtained and obturated with AH26 sealer and gutta-percha using lateral condensation technique. Three millimeters of the root end were cut off and randomly divided into 3 groups of 15 each (3 mixing methods of amalgamator, ultrasonic and conventional) and 2 negative and positive control groups (each containing 5 samples). BHI (brain-heart infusion agar) suspension containing Enterococcus faecalis was used for bacterial leakage assessment. Statistical analysis was carried out using descriptive statistics, Kaplan-Meier survival analysis with censored data and log rank test. Statistical significance was set at P<0.05. RESULTS: The survival means for conventional, amalgamator and ultrasonic methods were 62.13±12.44, 68.87±12.79 and 77.53±12.52 days, respectively. The log rank test showed no significant differences between the groups. CONCLUSIONS: Based on the results of the present study it can be concluded that different mixing methods had no significant effect on the bacterial microleakage of CEM cement.

Combination of simvastatin, calcium silicate/gypsum, and gelatin and bone regeneration in rabbit calvarial defects.

The present study was performed to determine whether simvastatin improves bone regeneration when combined with calcium silicate/gypsum and gelatin (CS-GEL). The surface morphology was determined using field-emission scanning electron microscopy (FSEM). Degradation in vitro was evaluated by monitoring the weight change of the composites soaked in phosphate buffered saline (PBS). Drug release was evaluated using high-performance liquid chromatography (HPLC). Cytotoxicity testing was performed to assess the biocompatibility of composites. Four 5 mm-diameter bone defects were created in rabbit calvaria. Three sites were filled with CS-GEL, 0.5 mg simvastatin-loaded CS-GEL (SIM-0.5) and 1.0 mg simvastatin-loaded CS-GEL (SIM-1.0), respectively, and the fourth was left empty as the control group. Micro-computed tomography (micro-CT) and histological analysis were carried out at 4 and 12 weeks postoperatively. The composites all exhibited three-dimensional structures and showed the residue with nearly 80% after 4 weeks of immersion. Drug release was explosive on the first day and then the release rate remained stable. The composites did not induce any cytotoxicity. The results in vivo demonstrated that the new bone formation and the expressions of BMP-2, OC and type I collagen were improved in the simvastatin-loaded CS-GEL group. It was concluded that the simvastatin-loaded CS-GEL may improve bone regeneration.

Dentinal Tubule Penetration of Tricalcium Silicate Sealers.

INTRODUCTION: The treatments for which mineral trioxide aggregate (MTA)-based materials can be used in dentistry are expanding. Smaller particle size and easier handling properties have allowed the advent of tricalcium silicate sealers including EndoSequence BC Sealer (Brasseler USA, Savannah, GA), QuickSet2 (Avalon Biomed, Bradenton, FL), NeoMTA Plus (Avalon Biomed), and MTA Fillapex (Angelus, Londrina, Brazil). The objective of this study was to measure the tubule penetration with these sealers using continuous wave (CW) and single-cone (SC) obturation techniques. METHODS: Eighty single-rooted teeth were randomly divided into 8 groups of 10 and obturated with 1 of the previously mentioned sealers mixed with trace amounts of rhodamine using either the CW or SC technique. Teeth were sectioned at 1 mm and 5 mm from the apex and examined under a confocal laser microscope. The percentage of sealer penetration and the maximum sealer penetration were measured. RESULTS: The tricalcium silicate sealers penetrated tubules as deep as 2000 µm (2 mm). The percentage of sealer penetration was much higher 5 mm from the apex, with many specimens having 100% penetration for both SC and warm vertical techniques. MTA Fillapex, a resin-based sealer with less than 20% MTA particles, had significantly greater tubule penetration with a warm vertical technique versus the SC technique at the 1-mm level. CONCLUSIONS: Within the limitations of this study, the CW and SC techniques produced similar tubule penetration at both the 1-mm and the 5-mm level with the tricalcium silicate sealers BC Sealer, QuickSet2, and NeoMTA Plus.

Mesoporous persistent nanophosphors for in vivo optical bioimaging and drug-delivery.

Based upon the ambitious idea that one single particle could serve multiple purposes at the same time, the combination and simultaneous use of imaging and therapeutics has lately arisen as one of the most promising prospects among nanotechnologies directed toward biomedical applications. Intended for both therapeutics and diagnostics in vivo, highly complex nanostructures were specifically designed to simultaneously act as optical imaging probes and delivery vehicles. Yet, such multifunctional photonic nanoplatforms usually exploit fluorescence phenomena which require constant excitation light through biological tissues and thus significantly reduce the detection sensitivity due to the autofluorescence from living animals. In order to overcome this critical issue, the present article introduces a novel multifunctional agent based on persistent luminescence mesoporous nanoparticles. Being composed of a hybrid chromium-doped zinc gallate core/mesoporous silica shell architecture, we show that this nanotechnology can be used as an efficient doxorubicin-delivery vehicle presenting a higher cytotoxicity toward U87MG cells than its unloaded counterpart in vitro. In addition, we demonstrate that a persistent luminescence signal from these doxorubicin-loaded mesoporous nanophosphors opens a new way to highly sensitive detection in vivo, giving access to the real-time biodistribution of the carrier without any autofluorescence from the animal tissues. This new persistent luminescence-based hybrid nanotechnology can be easily applied to the delivery of any therapeutic agent, thus constituting a versatile and sensitive optical nanotool dedicated to both therapeutic and diagnostic applications in vivo.

Effects of a chewing gum containing phosphoryl oligosaccharides of calcium (POs-Ca) and fluoride on remineralization and crystallization of enamel subsurface lesions in situ.

OBJECTIVES: Manufacturers are adding fluoride (F) to calcium-containing chewing gums to further promote enamel remineralization. The aim of this study was to assess the effect of a chewing gum containing phosphoryl oligosaccharides of calcium (POs-Ca) and fluoride on remineralization of enamel subsurface lesions, in a double-blind, randomized controlled in situ trial. METHODS: Thirty-six volunteer subjects wore removable buccal appliances with three different insets of bovine enamel with subsurface demineralized lesions. For 14 days the subjects chewed one of the three chewing gums (placebo, POs-Ca, POs-Ca+F), three times a day. After each treatment period, the insets were removed from the appliance, embedded, sectioned, polished and then subjected to laboratory tests; mineral level was determined by transverse microradiography (TMR; n=36), and hydroxyapatite (HAp) crystallites were assessed by synchrotron radiation wide-angle X-ray diffraction (WAXRD; n=13). Data were analysed by t-test or Wilcoxon rank-sum test with Bonferroni corrections at 0.05 significance level. RESULTS: Chewing POs-Ca and POs-Ca+F gums resulted in 21.9±10.6 and 26.3±9.4 (mean±SD) percentage mineral recovery, which was significantly higher than that of placebo gum (15.0±11.4) (p<0.05). Chewing POs-Ca+F gum resulted in 24.9±5.4 (mean±SD) percentage HAp crystallites recovery, which was significantly higher compared to POs-Ca (16.0±4.1%) or placebo (11.1±4.8%) gums (p<0.05). CONCLUSIONS: Addition of POs-Ca to the chewing gum resulted in significant remineralization of enamel subsurface lesions. Although POs-Ca+F gum was not superior in TMR recovery rate when compared with POs-Ca gum, WAXRD results highlighted the importance of fluoride ion bioavailability in the formation of HAp crystallites in enamel subsurface lesions in situ (NCT01377493).

Effects of intracanal mineral trioxide aggregate and calcium hydroxide during four weeks on pH changes in simulated root surface resorption defects: an in vitro study using matched pairs of human teeth.

INTRODUCTION: Diffusion of hydroxyl ions from intracanal calcium hydroxide (CH) through dentin is used to arrest external inflammatory root resorption. However, long-term and short-term CH placement has been associated with an increased risk of root fracture. Intracanal mineral trioxide aggregate (MTA) might provide an alternative to CH as a source of hydroxyl ions. This in vitro study compared the effects of intracanal MTA and CH on hydroxyl ion diffusion through dentin by measuring pH changes over time in simulated root surface resorption defects prepared in matched pairs of teeth; the null hypothesis tested was that there is no difference. METHODS: Root surface cavities were prepared 5 mm from the apex in extracted human permanent anterior teeth (21 matched pairs) and 7 additional teeth (controls). Root canals were instrumented to size 50/.04 and filled with either tooth-colored MTA (ProRoot) or CH (UltraCal XS); control teeth were filled with saline. The pH in root surface cavities was measured at 3 hours, 24 hours, 1 week, 2 weeks, 3 weeks, and 4 weeks. RESULTS: In controls, pH readings did not differ significantly during the 4 weeks (P > .05, repeated-measures analysis of variance [ANOVA]). For the experimental intragroup effects, significant pH changes occurred over time in the MTA group (P = .005, repeated-measures ANOVA) and the CH group (P < .0001). For the experimental intergroup effects, the overall mean pH was higher in the MTA group (8.66; standard error [SE], 0.07) compared with the CH group (8.46; SE, 0.07) (P = .014, paired t test). At 4 weeks pH was higher in the MTA group (8.30; SE, 0.16) compared with the CH group (7.90; SE, 0.11) (P = .011); at all other time points intergroup differences were insignificant. The null hypothesis was rejected. CONCLUSIONS: Intracanal MTA and CH groups differed in their overall effect on pH measured in simulated root surface resorption defects. At 4 weeks intracanal placement of MTA compared with CH resulted in a small but significantly higher pH.

Free acid gel form of ß-hydroxy-ß-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt.

The leucine metabolite, ß-hydroxy-ß-methylbutyrate (HMB), is a nutritional supplement that increases lean muscle and strength with exercise and in disease states. HMB is presently available as the Ca salt (CaHMB). The present study was designed to examine whether HMB in free acid gel form will improve HMB availability to tissues. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (sem 11), 38 (sem 4) and 38 (sem 1) min (P < 0·0001) for CaHMB, FASW and FASL, respectively. The peak concentrations were 131 (sem 6), 249 (sem 14) and 239 (sem 14) µmol/l (P < 0·0001) for CaHMB, FASW and FASL, respectively. The areas under the curve were almost double for FASW and FASL (P < 0·0001). Daily urinary HMB excretion was not significantly increased resulting in more HMB retained (P < 0·003) with FASW and FASL. Half-lives were 3·17 (sem 0·22), 2·50 (sem 0·13) and 2·51 (sem 0·14) h for CaHMB, FASW and FASL, respectively (P < 0·004). Free acid gel resulted in quicker and greater plasma concentrations (+185%) and improved clearance (+25%) of HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease.

Evaluation of composts and liming materials in the phytostabilization of a mine soil using perennial ryegrass.

A microcosm experiment was carried out to evaluate the effects of municipal solid waste compost (MSWC) or garden waste compost (GWC), and liming materials in the rehabilitation of a soil affected by mining activities, and to study the use of perennial ryegrass (Lolium perenne L.) for phystostabilization. The performance of the amendments was assessed by soil chemical parameters, total and bioavailable metals (Cu, Pb and Zn), soil enzymatic activities, and plant relative growth and mineral composition. In general, both composts corrected soil acidity and increased the total organic matter content of the soil, although with a better performance in the case of MSWC, especially when considering total N and available P and K levels in the amended soil. The application of both composts and liming materials led to a decrease in the mobile fractions of Cu, Pb and Zn, but mobilisable fractions of Cu and Zn increased with MSWC application. Plant biomass increased more than three times in the presence of 50 Mg MSWC ha(-1) and with the combined use of 25 or 50 Mg MSWC ha(-1) and CaO, but no significant differences were observed when GWC was applied. Plant tissue analysis showed that the treatments did not significantly reduce Cu, Pb and Zn uptake by the plant. Dehydrogenase, and the enzymes related to the N-cycle, urease and protease, had increased activities with increasing MSWC application rate. Conversely, the enzymatic activities of both enzymes related to the C-cycle, cellulase and beta-glucosidase, were only positively affected by GWC application, a compost obtained from raw materials rich in C. Principal component analyses evidenced this clear separation between the effect of MSWC on soil enzymes related to the N-cycle and of GWC on soil enzymes related to the C-cycle. This study indicates that MSWC (50 Mg ha(-1), limed or unlimed) can be used successfully in the remediation of a highly acidic metal-contaminated soil, allowing the establishment of perennial ryegrass.

Calcium ion diffusion from mineral trioxide aggregate through simulated root resorption defects.

The purpose of this study was to investigate the diffusion of calcium ions (Ca+2) through exposed dentinal tubules following intracanal application of mineral trioxide aggregate (MTA). Fifty-two single-rooted teeth were instrumented using 2.5% sodium hypochlorite for irrigation between each file size. Thereafter, standardized defects were created on the root surfaces so as to mimic external root resorption. The root canals and external defects received a final irrigation of 17% ethylenediaminetetraacetic acid and distilled water. MTA powder was then mixed with saline and placed into the canals. All root surfaces except the cavities were sealed with two coats of varnish. Teeth with unfilled canals (n = 26) served as controls. The teeth were immersed in saline after which the release of Ca+2 from the defects into the saline was measured at 1, 3, 7, 14, and 28 days. The results showed diffusion of Ca+2 through the defects in the dentin in MTA-filled roots with a significant increase in concentration within time.

Fluoride concentrations in dental plaque and saliva after the use of a fluoride dentifrice preceded by a calcium lactate rinse.

Plaque fluoride concentrations ([F]) are directly related to plaque calcium concentrations [Ca]. Attempts to increase plaque F uptake from dentifrices or rinses have used methods designed to increase plaque [Ca] but with inconsistent results. This double-blind, double-crossover study tested the effect of a 150 mM calcium lactate rinse used prior to brushing with placebo or fluoridated dentifrices (1030 p.p.m. as NaF) on plaque and salivary [F] and [Ca]. Sixteen children (8-10 yr of age) were randomly assigned to four different groups according to the four treatments (placebo dentifrice or fluoridated dentifrice preceded by calcium lactate or deionized water prerinses). Plaque and saliva were collected 1 and 12 h after brushing on day 7 after starting to use the dentifrices. F was determined using the electrode and Ca was determined using atomic absorption spectrometry. Plaque and salivary [Ca] were not significantly increased after use of the calcium lactate prerinse, except for plaque [Ca] 1 h after the use of the placebo dentifrice. A significant increase in salivary [F] was associated with the calcium lactate prerinse only at 1 h after the use of the fluoridated dentifrice. The the calcium lactate prerinse did not significantly affect plaque [F] under any condition.

A novel calcium silicate based microspheres of repaglinide: in vivo investigations.

The objective of the present investigation was to evaluate gastro-retentive performance and pharmacokinetic parameters of optimized floating microspheres (RgFMCS4) consisting of (i) calcium silicate (CS) as porous carrier; (ii) repaglinide (Rg), an oral hypoglycemic agent; and (iii) Eudragit S (ES) as polymer. The optimized formulation demonstrated favorable in-vitro-floating and drug release characteristics. The gastro-retentive behavior of this optimized formulation was compared with non-floating microspheres (RgNFM) prepared from the identical polymer. Stability test of (99m)Tc-labeled formulations were carried out using appropriate standard buffer solutions of pH 2.0, 6.8 and 7.4. The organ distribution study was performed in albino rats in order to measure labeling efficiency of the formulation with (99m)Tc. The gamma scintigraphy of the formulations was carried out in albino rabbits to monitor the transit of RgFMCS4 and RgNFM in the gastrointestinal (GI) tract. Prolonged gastric residence time (GRT) of over 6 h was achieved in all animals for calcium silicate based floating microspheres of Rg. Rg loaded optimized formulation was orally administered to albino rabbits and blood samples were used to determine pharmacokinetic parameters of Rg from floating microspheres, which were compared with pharmacokinetic parameters of the marketed tablet formulation. The relative bioavailability of Rg loaded floating microspheres was found to be increased about 3.17 times in comparison to that of the marketed tablet. The enhanced bioavailability and eliminated half-lives of Rg formulation observed in the present study are attributed to the floating nature of the designed formulations.