Impact of pH-adjusted fluoride and stannous solutions on the protective properties on the pellicle layer in vitro and in situ.

This study evaluates the ideal pH for anti-erosion and anti-adherent efficacy of fluoride and stannous solutions (sodium fluoride (SF), amine fluoride (AF), sodium monofluorophosphate (SMFP), stannous fluoride (SnF2) with 500 ppm fluoride concentration each and stannous chloride (SnCl2, 1563 ppm stannous)). In vitro, solutions were tested at pH 4.5 and 5.5. The main in situ experiments were carried out at the pH of 4.5: For pellicle formation 6 volunteers wore bovine enamel slabs intraorally for 1 min, rinsed with 8 ml solution for 1 min and continued for up to 30 min/8 h. Physiological pellicle samples served as controls. After incubation in HCl (2.0, 2.3) for 2 min mineral release was determined photometrically. Bacterial counts on 8 h biofilms were determined by fluorescence microscopy (BacLight™ and DAPI with Concanavalin A). Modification of the pellicle ultrastructure was examined by TEM. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney-U tests with Bonferroni-correction (p < 0.05). SnF2 showed a significant erosion protection. AF, SnF2, and SnCl2 were most anti-adherent. SnF2 and SnCl2 caused a pronounced basal pellicle with stannous precipitates. Compared to other fluoride monosubstances, stannous ions offer greater protection against erosive acidic attacks. Stannous ions act as crucial co-factor in this process.

Film-Forming Polymers for Inhibition of Hydroxyapatite Dissolution: A Screening Study.

The aim of this study was to evaluate the effect of film-forming polymer solutions of different concentrations and pH values, either associated or not with sodium fluoride (F; 225 ppm F-), when applied during the initial stage of salivary pellicle formation, to prevent the dissolution of hydroxyapatite (HA), which was determined by the pH-stat method. Polyacrylic acid (PA), chitosan, sodium linear polyphosphate (LPP), polyvinyl methyl ether/maleic anhydride (PVM/MA), and propylene glycol alginate (PGA) were tested in three concentrations (lower, medium, and higher), two pH values (native or adjusted), and either associated or not with F. Distilled water, F, and stannous ion+fluoride (Sn/F; 225 ppm F- and 800 ppm Sn2+, as SnCl2) solutions were the controls, totalizing 63 groups. HA crystals were pretreated with human saliva for 1 min to allow pellicle formation, then immersed in the experimental solutions (1 min), and exposed to saliva for another 28 min. Subsequently, they were added to a 0.3% citric acid solution (pH = 3.8), connected to a pH-stat system that added aliquots of 28 µL 0.1 N HCl for a total reaction time of 5 min. Data were analyzed with one-way ANOVA and Tukey's tests (α = 0.05). For PA alone, the concentrations of 0.1% (native pH), 0.06%, and 0.08% (both pH adjusted) showed significantly lower HA dissolution than the negative control. PA concentrations of 0.1% and 0.08%, of both pH values, improved the effect of F against HA dissolution to a near-identical value as Sn/F. All solutions containing chitosan and LPP significantly reduced HA dissolution in comparison with the control. For chitosan, the concentration of 0.5% (in both pH values) improved the effect of F. LPP at 0.5% (native pH) and all associations of LPP with F outperformed the effect of F. Some PVM/MA solutions significantly reduced HA dissolution but PVM/MA could not improve the protection of F. PGA was incapable of reducing HA dissolution or improving F effect. It was concluded that chitosan, LPP, and some PA and PVM/MA solutions used alone were capable of reducing HA dissolution. Only PA, chitosan, and LPP were able to enhance fluoride protection, but for PA and chitosan, this was influenced by the polymer concentration.

In vivo assessment of the corrosion of nickel-titanium orthodontic archwires by using scanning electron microscopy and atomic force microscopy.

This study was undertaken to assess in vivo the corrosion in two commercial nickel-titanium (NiTi) orthodontic archwires removed from the oral cavity of patients using fluoride mouthwashes. Five volunteers took part in this study on the corrosion behavior of two brands of NiTi archwires (3M and AO (brand of archwire)) during use of two mouthwashes with neutral sodium fluoride 1.1%, one with acidulated fluoride 1.1%, and one with placebo and a control group. Each patient used one mouthwash in three different periods of time for 1 min a day for 30 days. The archwires were assessed with scanning electron microscopy and atomic force microscopy for qualitative and quantitative analysis. The values obtained with atomic force microscopy (AFM) were submitted to normality test, two-way analysis of variance, and Tukey's test at a significance level of 5%. The AFM images showed a gradual qualitative increase in the roughness of both types of wire between the treatments: control < placebo < neutral fluoride < acidulated fluoride. The arithmetic average of the roughness and root mean square of the roughness were similar. As for 3M archwires, only the acidulated fluoride group differed statistically from the others. As for AO archwires, the control and placebo groups did not differ from each other, but differed from the other fluoride treatments. The group using neutral fluoride also differed significantly from the acidulated fluoride group. 3M archwires were not affected by daily oral challenges. AO archwires were not affected by daily oral challenges either; their association with fluoride, either neutral or acidulated, increased their roughness.

18F-Sodium Fluoride PET: History, Technical Feasibility, Mechanism of Action, Normal Biodistribution, and Diagnostic Performance in Bone Metastasis Detection Compared with Other Imaging Modalities.

The skeleton is the third most common site for metastasis overall, after the lungs and liver. Accurate diagnosis of osseous metastasis is critical for initial staging, treatment planning, restaging, treatment monitoring, and survival prediction. Currently, 99mTc-methylene diphosphonate whole-body scanning is the cornerstone of imaging to detect osseous metastasis. Although 18F-sodium fluoride (18F-NaF) was one of the oldest medical tracers for this purpose, it was replaced by other tracers because of their better physical properties, until recently. Continued development of PET scanners has opened a new era for 18F-NaF, and given its higher sensitivity, there have been increasing applications in imaging. In this review, we will discuss the history, technical aspects, radiobiology, and biodistribution of this tracer. Finally, we compare the accuracy of 18F-NaF PET with other conventional imaging methods for detection of osseous metastasis.

Size-Dependent Photothermal Conversion and Photoluminescence of Theranostic NaNdF4 Nanoparticles under Excitation of Different-Wavelength Lasers.

The narrow absorption and emission bands, long fluorescence lifetime, and excellent stability of rare earth nanoparticles (referred to as RE NPs) make them very attractive for multimodal imaging and therapy of cancer. Their narrow absorption requires the careful selection of laser wavelength to achieve the best performance, particularly for RE NPs simultaneously having photothermal and photoluminescent properties (e.g., Nd-based nanoparticles), which has not been investigated. Herein, we prepared a series of different-sized NaNdF4 nanoparticles (referred to as NNF NPs) (i.e., 4.7, 5.9, 12.8, and 15.6 nm) from ultrasmall nanoclusters and investigated their in vitro and in vivo size-dependent photothermal conversion and photoluminescence under irradiation by a 793 nm laser and an 808 nm laser, respectively. We find that all nanoparticles exhibited the better photothermal conversion performance under the irradiation of the 808 nm laser than under the 793 nm laser, of which 12.8 nm NNF NPs showed the best performance, and the temperature of their solution can be quickly increased from 30 °C to around 60 °C within 10 min under the irradiation of the 808 nm laser with a power intensity of 0.75 W/cm2. When we used the 793 nm laser to excite these NNF NPs, we found that all nanoparticles exhibited the stronger photoluminescence in the second near-infrared window (NIR-II) than under the excitation by the 808 nm laser, of which 15.6 nm NNF NPs possessed the strongest NIR-II luminescence. We then modified 12.8 nm NNF NPs with phospholipid carboxyl PEG and functionalized with RGD for actively targeted imaging of cancer. The NaNdF4@PEG@RGD nanoparticles (referred to as NNF-P-R NPs) have good biocompatibility, stability, and excellent targeting capability. The in vivo result show that 12.8 nm NNF NPs exhibited better photothermal conversion performance under the irradiation of the 808 nm laser, and stronger NIR-II fluorescence under irradiation of the 793 nm laser, which are consistent with the in vitro result. This work demonstrates the significance of selection of the proper laser wavelength for maximally taking advantage of RE nanoparticles for the diagnosis and treatment of cancer.

Purification and characterization of latent polyphenol oxidase from truffles (Terfezia arenaria).

The polyphenol oxidase was extracted and purified from truffles (Terfezia arenaria) and it exhibited a molecular weight of 67 kDa. The truffle PPO was able to oxidize monophenolic, o-diphenolic and triphenolic substrates. Thus, the enzyme seems to be stable under wide range of pH and temperature. Best catalytic efficiency was observed for catechol as substrate (Kcat/km; 674.2 S-1 mM-1).The effect of detergents, chaotropic agents, metal ions and eleven different inhibitors on relative activity of Truffles PPO was also investigated. A latent form of enzyme was observed and its activity was stimulated using 4 mM of SDS. Likewise, the type of inhibition and the values of KI and IC50 were reported for L-cysteine, Sodium fluoride, sodium metabisulfite and kojic acid. Besides, the effect of four concentrations of kojic acid(0.05.,0.1.,0.2 and 0.3 mM) on thermal inactivation of PPO was performed in temperature range " 60-75° C". The use of Kojic acid increase the rate of inactivation process and disrupt enzymatic activity. Moreover, the combined effect of temperature and kojic acid prevent from enzymatic browning reaction and maintain high antioxidant activities including ABTS scavenging activity, FRAP, and total phenolic contents.

18 F-NaF PET/CT IMAGING IN FIBROUS DYSPLASIA OF BONE.

Fibrous dysplasia (FD) is a mosaic skeletal disorder resulting in fractures, deformity, and functional impairment. Clinical evaluation has been limited by a lack of surrogate endpoints capable of quantitating disease activity. The purpose of this study was to investigate the utility of 18 F-NaF PET/CT imaging in quantifying disease activity in patients with FD. Fifteen consecutively evaluated subjects underwent whole-body 18 F-NaF PET/CT scans, and FD burden was assessed by quantifying FD-related 18 F-NaF activity. 18 F-NaF PET/CT parameters obtained included (i) SUVmax (standardized uptake value [SUV] of the FD lesion with the highest uptake); (ii) SUVmean (average SUV of all 18 F-NaF-positive FD lesions); (iii) total volume of all 18 F-NaF-positive FD lesions (TV); and (iv) total FD lesion activity determined as the product of TV multiplied by SUVmean (TA = TV × SUVmean ) (TA). Skeletal outcomes, functional outcomes, and bone turnover markers were correlated with 18 F-NaF PET/CT parameters. TV and TA of extracranial FD lesions correlated strongly with skeletal outcomes including fractures and surgeries (p values ≤ 0.003). Subjects with impaired ambulation and scoliosis had significantly higher TV and TA values (P < 0.05), obtained from extracranial and spinal lesions, respectively. Craniofacial surgeries correlated with TV and TA of skull FD lesions (P < 0.001). Bone turnover markers, including alkaline phosphatase, N-telopeptides, and osteocalcin, were strongly correlated with TV and TA (P < 0.05) extracted from FD lesions in the entire skeleton. No associations were identified with SUVmax or SUVmean . Bone pain and age did not correlate with 18 F-NaF PET/CT parameters. FD burden evaluated by 18 F-NaF-PET/CT facilitates accurate assessment of FD activity, and correlates quantitatively with clinically-relevant skeletal outcomes. © 2019 American Society for Bone and Mineral Research.

Evolution of heterotopic bone in fibrodysplasia ossificans progressiva: An [18F]NaF PET/CT study.

Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede the formation of HO, resulting in immobilization of joints. Due to progression of the disease without signs of a flare-up, co-existence of a chronic progression of HO has been postulated, but conclusive evidence is lacking. Recently, it has been shown that [18F]NaF PET/CT is able to identify early ossifying disease activity during flare-ups. Therefore, the purpose of the present study was to assess whether [18F]NaF PET/CT might also be able to identify the possible presence of chronic progressive HO in FOP. A total of thirteen [18F]NaF PET/CT scans from five FOP patients were analysed. Scans were acquired over a period of 0.5 to 2 years. Volumes of HO and standardized uptake values (SUV) were obtained based on manual segmentation of CT images. SUVpeak values, defined as the average SUV value of a 1 mL sphere containing the hottest voxel pixels, were obtained. Two out of five patients experienced ≥1 active clinical flare-ups at the time of the [18F]NaF PET/CT scan. In addition, in four out of five patients, serial scans showed radiological progression of HO (3 to 8 cm3), as assessed by CT volume, in the absence of a clinical flare-up. This volumetric increase was present in 6/47 (12.8%) of identified HO structures and, in all cases, was accompanied by increased [18F]NaF uptake, with SUVpeak ranging from 8.4 to 17.9. In conclusion, HO may progress without signs of a flare-up. [18F]NaF PET/CT is able to identify these asymptomatic, but progressive HO lesions, thereby demonstrating the presence of chronic activity in FOP. Consequently, future drugs should not only target new HO formation, but also this chronic HO progression.

Biocompatible Glycine-Assisted Catalysis of the Sol-Gel Process: Development of Cell-Embedded Hydrogels.

The sol-gel process can be used for hydrogel cross-linking, thus opening an attractive route for the design of biocompatible hydrogels under soft conditions. The sol-gel process can be catalysed at basic or acidic pH values, under neutral conditions with the addition of a nucleophile. Therefore, working around pH 7 unlocks the possibility of direct cell embedment and the preparation of bioinks. We aimed to propose a generic method for sol-gel 3D bioprinting, and first screened different nucleophilic catalysts using bis-silylated polyethylene glycol (PEG) as a model hydrogel. A synergistic effect of glycine and NaF, used in low concentrations to avoid any toxicity, was observed. Biocompatibility of the approach was demonstrated by embedding primary mouse mesenchymal stem cells. The measure of viscosity as a function of time showed the impact of reaction parameters, such as temperature, complexity of the medium, pH and cell addition, on the kinetics of the sol-gel process, and allowed prediction of the gelation time.

Anti-Erosive Effect of Solutions Containing Sodium Fluoride, Stannous Chloride, and Selected Film-Forming Polymers.

The aim of this study was to evaluate the anti-erosive effect of solutions containing sodium fluoride (F: 225 ppm F-), stannous chloride (Sn: 800 ppm Sn2+), and some film-forming polymers (Gantrez: Poly [methylvinylether-alt-maleic anhydride]; PGA: propylene glycol alginate; Plasdone: poly[vinylpyrrolidone]; and CMC: carboxymethylcellulose). Solutions were tested in an erosion-remineralization cycling model, using enamel and dentin specimens (n = 10, for each substrate). Distilled water was the negative control. Cycling consisted of 120 min immersion in human saliva, 5 min in 0.3% citric acid solution, and 120 min of exposure to human saliva, 4×/day, for 5 days. Treatment with solutions (pH = 4.5) was carried out 2×/day, for 2 min. Surface loss (SL) was evaluated with optical profilometry. Zeta potential of hydroxyapatite crystals was determined after treatment with the solutions. Data were statistically analyzed (α = 0.05). For enamel, all polymers showed significantly lower SL (in µm) than the control (11.09 ± 0.94), except PGA (10.15 ± 1.25). PGA significantly improved the protective effect of F (4.24 ± 0.97 vs. 5.64 ± 1.60, respectively). None of the polymers increased the protection of F+Sn (5.13 ± 0.78). For dentin, only Gantrez (11.40 ± 0.97) significantly reduced SL when compared with the negative control (12.76 ± 0.75). No polymer was able to enhance the effect of F (6.28 ± 1.90) or F+Sn (7.21 ± 1.13). All fluoridated solutions demonstrated significantly lower SL values than the control for both substrates. Treatment of hydroxyapatite nanoparticles with all solutions resulted in more negative zeta potentials than those of the control, except Plasdone, PGA, and F+Sn+PGA, the latter two presenting the opposite effect. In conclusion, Gantrez, Plasdone, and CMC exhibited an anti-erosive effect on enamel. PGA increased the protection of F. For dentin, only Gantrez reduced erosion.

Effect of a resin-modified glass-ionomer with calcium on enamel demineralization inhibition: an in vitro study

Abstract We assessed the effect of a new coating material based on resin-modified glass-ionomer with calcium (Ca) in inhibiting the demineralization of underlying and adjacent areas surrounding caries-like lesions in enamel. The measures used were surface hardness (SH) and cross-sectional hardness (CSH). Thirty-six bovine enamel specimens (3 × 6 × 2 mm) were randomly allocated into three groups (n = 12): No treatment (NT); resin-modified glass-ionomer with Ca (Clinpro XT Varnish, 3M ESPE) (CL), and fluoride varnish (Duraphat, Colgate) (DU). The specimens were subjected to alternated immersions in demineralizing (6 h) and remineralizing solutions (18 h) for 7 days. SH measurements were conducted at standard distances of 150, 300, and 450 µm from the treatment area. CSH evaluated the mean hardness profile over the depth of the enamel surface and at standard distances from the materials. The energy-dispersive X-ray spectroscopy analysis was conducted to evaluate the demineralization bands created on the sublayer by % of calcium (Ca), phosphorus (P), and fluoride (F). Ca/P weight ratio was also calculated. Based on SH and CSH measurements, there was no difference between groups at the distances 150 µm (p = 0.882), 300 µm (p = 0.995), and 450 µm (p = 0.998). Up to 50 µm depth (at 150 µm from the treatment area), CL showed better performance than DU ( p< 0.05). NT presented higher loss of Ca and P than CL and DU (p < 0.05). There was no significant difference in the % of F ion among the three groups. The new coating material was similar to F varnish in attenuating enamel demineralization.

Fluoride release and uptake in enhanced bioactivity glass ionomer cement ("glass carbomer™") compared with conventional and resin-modified glass ionomer cements

Abstract Objectives To study the fluoride uptake and release properties of glass carbomer dental cements and compare them with those of conventional and resin-modified glass ionomers. Materials and Methods Three materials were used, as follows: glass carbomer (Glass Fill), conventional glass ionomer (Chemfil Rock) and resin-modified glass ionomer (Fuji II LC). For all materials, specimens (sets of six) were matured at room temperature for time intervals of 10 minutes, 1 hour and 6 weeks, then exposed to either deionized water or sodium fluoride solution (1000 ppm in fluoride) for 24 hours. Following this, all specimens were placed in deionized water for additional 24 hours and fluoride release was measured. Results Storage in water led to increase in mass in all cases due to water uptake, with uptake varying with maturing time and material type. Storage in aqueous NaF led to variable results. Glass carbomer showed mass losses at all maturing times, whereas the conventional glass ionomer gained mass for some maturing times, and the resin-modified glass ionomer gained mass for all maturing times. All materials released fluoride into deionized water, with glass carbomer showing the highest release. For both types of glass ionomer, uptake of fluoride led to enhanced fluoride release into deionized water. In contrast, uptake by glass carbomer did not lead to increased fluoride release, although it was substantially higher than the uptake by both types of glass ionomer. Conclusions Glass carbomer resembles glass ionomer cements in its fluoride uptake behavior but differs when considering that its fluoride uptake does not lead to increased fluoride release.

Comparison of 18F-NaF PET/CT and 18F-FDG PET/CT for Detection of Skull-Base Invasion and Osseous Metastases in Nasopharyngeal Carcinoma.

Our study aimed at comparing the diagnostic value of 18F-NaF positron emission tomography-computed tomography (PET/CT) and 18F-fluorodeoxyglucose (FDG) PET/CT for detection of skull-base invasion and osseous metastases in patients with nasopharyngeal carcinoma (NPC). Our study retrospectively analyzed 45 patients with pathologically proven NPC. They all underwent both 18F-NaF PET/CT and 18F-FDG PET/CT within a 7-day interval. Bone metastases were confirmed by follow-up using PET/CT, enhance-contrast computed tomography (CT), and magnetic resonance image (MRI). These two examinations were compared using per-patient-based analysis and per-lesion-based analysis. 18F-NaF PET/CT detected 27 patients with skull-base invasion, whereas 18F-FDG PET/CT detected 17 patients. 18F-NaF PET/CT and 18F-FDG PET/CT differed significantly in diagnosing skull-base invasion (p=0.02) and sensitivity (p=0.008). The sensitivity, specificity, and agreement rate of 18F-NaF PET/CT for detecting bone metastatic lesions were 98.3%, 65.7%, and 92.9%, respectively; these values were 42.9%, 97.1%, and 51.9%, respectively, for 18F-FDG PET/CT. 18F-NaF PET/CT and 18F-FDG PET/CT differed significantly in the number of osseous metastases detected (t=2.45, p=0.18) sensitivity (p < 0.0001) and specificity (p=0.003). In patients with nasopharyngeal carcinoma, 18F-NaF PET/CT assessed invasion of the skull base better and detected more osseous metastases than 18F-FDG PET/CT.

Fluorination Enhances the Osteogenic Capacity of Porcine Hydroxyapatite.

In a previous study, we successfully prepared fluorinated porcine hydroxyapatite (FPHA) by immersing porcine hydroxyapatite (PHA) in an aqueous solution of 0.25 M sodium fluoride (NaF) under thermal treatment, and the resulting FPHA showed better physicochemical and biological properties than PHA. The purpose of this study was to further investigate how fluorine incorporation influenced the biocompatibility and osteogenic capacity of PHA. The concentrations of Ca, P, F, and Mg ions in PHA and FPHA extracts were detected by inductively coupled plasma optical emission spectrometry. Rat bone marrow stromal cells (rBMSCs) were treated with PHA and FPHA extracts, and the effects of these extracts on cell proliferation and osteoblastic differentiation were evaluated via Cell Counting Kit-8 assay, alkaline phosphatase assay, and real time-quantitative polymerase chain reaction. For the in vivo assessment, PHA and FPHA were implanted into subcutaneous pockets (n = 6) and rat calvarial defects (diameter = 5 mm, n = 14) for 12 weeks to determine their biocompatibility and osteogenic capacity by using micro-computed tomography (CT) and histological analysis. FPHA extracts, which release higher concentrations of F and Mg ions, better promoted the osteoblastic differentiation of rBMSCs in vitro. The result of biocompatibility evaluation confirmed that the host response and chronic inflammation cells infiltration degree around PHA and FPHA granules were similar. Micro-CT and histological analysis showed newer mineralized bone formation in rats with FPHA-treated defects than in rats with PHA-treated defects. The results of in vitro and in vivo tests consistently indicate that fluorine incorporation effectively enhanced the osteogenic capacity of PHA.

TiF4 varnish protects the retention of brackets to enamel after in vitro mild erosive challenge

Abstract The effect of fluoride agents on the retention of orthodontic brackets to enamel under erosive challenge is little investigated. Objective: The aim of this study was to evaluate the effect of titanium tetrafluoride (TiF4) and sodium fluoride (NaF) agents on the shear bond strength of brackets to enamel and on the enamel microhardness around brackets under erosive challenge. Methods: Brackets were bonded to bovine incisors. Five groups were formed according to fluoride application (n=10): TiF4 varnish, TiF4 solution, NaF varnish, NaF solution and control (without application). The specimens were submitted to erosive challenge (90 s cola drink/2h artificial saliva, 4x per day for 7 days). Solutions were applied before each erosive cycle and varnishes were applied once. Vickers Microhardness (VHN) was obtained before and after all cycles of erosion and the percentage of microhardness loss was calculated. Shear bond strength, adhesive remnant index and polarized light microscopy were conducted after erosion. The data were analyzed by ANOVA, Tukey, Kruskal-Wallis and Mann-Whitney U tests (α=0.05). Results: The %VHN had no statistically significant differences among the experimental groups. However, considering the comparisons of all groups with the control group, TiF4 varnish showed the highest protection from enamel demineralization (effect size of 2.94, while the effect size for the other groups was >2.4). The TiF4 varnish group had significantly higher shear bond strength compared to other groups. There was no difference among groups for adhesive remnant index. Polarized light microscopy showed higher demineralization depth for the control group. Conclusions: Application of NaF and TiF4 agents during mild erosive challenge minimized the enamel mineral loss around brackets, however only the experimental TiF4 varnish was able to prevent the reduction of shear bond strength of brackets to enamel.

DNA-assisted upconversion nanoplatform for imaging-guided synergistic therapy and laser-switchable drug detoxification.

The side effects of chemotherapy bring significant physical and psychological suffering to patients. To solve this urgent medical problem, Yb3+ and Er3+ co-doped NaLuF4 upconversion nanoparticles (UCNPs) were constructed for upconversion luminescence (UCL)-labeled diagnosis under 980 nm laser irradiation. The UCNPs were then modified layer by layer with polypyrrole and a special programming DNA segment as photothermal conversion agents and controllable drug carriers, respectively. The nanoplatform was successfully used for imaging-guided synergistic therapy (photothermal therapy and chemotherapy) at a safe power density (300 mW cm-2), and DNA-assisted detoxification at lower temperature in cancer cells when the laser off. The synergistic therapy of the nanoplatform achieved a higher therapeutic index (∼85%) than chemotherapy only (∼44%) and photothermal therapy only (∼25%) in vitro. In vivo experiments also suggested that the nanoplatform had a higher therapeutic effect and lower side effects. The toxicity study was also evaluated, indicating the nanoplatform is low toxic to living system. This multifunctional upconversion nanoplatform provided an innovative method for imaging-guided photothermal-chemotherapy and laser-switchable drug detoxification.

Papel das proteases na erosão dentinária / The role of proteases on dental erosion

Na dentina, a matriz orgânica desmineralizada tem um papel protetor contra desafios erosivos subsequentes. Porém, essa camada pode ser degradada por proteases, como as metaloproteinases da matriz (MMPs) e cisteína catepsinas (CCs). Recentemente, o uso de inibidores de proteases da matriz surgiu como uma importante ferramenta preventiva contra a erosão dentinária. Entretanto, o(s) mecanismo(s) exato(s) pelo(s) qual(is) os inibidores de proteases podem prevenir a erosão dentinária, bem como os tipos de proteases mais envolvidas neste processo ainda não são completamente conhecidos. O projeto foi desenvolvido em 2 subprojetos, com os seguintes objetivos: A)Subprojeto 1:Avaliar o papel das proteases na progressão da erosão dentária; B)subprojeto 2: Testar o potencial inibitório do NaF em CCs dentinárias. Para cumprir esses objetivos, foram utilizadas dentina de terceiros molares humanos para a preparação dos espécimes. A)Subprojeto1:Blocos de dentina (4 X 4 x 2 mm) (n=119) foram obtidos de raízes. Os espécimes foram divididos em 7 grupos de acordo com o seu tratamento (E-64, inibidor especifico II de catepsinas B, clorexidina, galardina NaF, placebo) ou sem tratamento, géis foram aplicados uma única vez sobre a superfície e feito o desafio erosivo (90s, 4x por dia por 5 dias) e feita analise perfilométrica. Os espécimes foram incubadas em solução contendo colagenase de Clostridium histolyticum tipo VII por 96hrs e então feita uma segunda analise perfilometrica para se determinar a espessura da MOD. Dois espécimes foram separados para análise de microscopia eletrônica de varredura. B)Subprojeto 2: Palitos de dentina (6 mm X 2 mm X 1 mm) (n=60) foram cortados da porção médio coronária dos dentes e completamente desmineralizados por imersão em EDTA 0,5 M (pH7,4) por 30 dias e lavados em água deionizada sob constante agitação a 4ºC por 72 h. Os espécimes foram divididos em 6 grupos (E-64, NaF e controle negativo, pH 5,5 ou 7,2) e incubados em saliva artificial contendo seus respectivos inibidores por 24 h 7 dias e 21 dias; ao termino de cada período, os espécimes eram pesados para avaliar a perda de massa e analisada a presença de CTX. A)Subprojeto 1: a perda de tecido desmineralizado (m, média± SD) foi: CHX 8,4±1,7b, Gala 8,6±1,9b, IECB 9,6±1,4a, E64 9,9±1,3a, NaF 9,9±1,7a, P 10,9±2,2a, ST 11,0±1,5a. A perda de tecido mineralizado foi: CHX 15,4±2,2b, Gala 16,0±1,8b, IECB 17,6±2,4a, E64 17,6±2,0a, NaF 17,3±2,8a, P 19,1±2,1a, ST 18,9±2,4a. Os inibidores de MMP reduziu significativamente a perda de matriz orgânica e tecido mineralizado em comparação com os outros grupos (p<0,05). Não foi achada diferença significante entre a espessura da matriz orgânica desmineralizada remanescente (p=0,845). B)Subprojeto 2: Na perda de massa houve diferença significante em relação ao inibidor (F=20,047, p<0,0001) e tempo de incubação (F=222,462, p<0,0001) com significante interação entre esses critérios, nos período de menor tempo de incubação, a perda foi similar para todos os grupos testados, no período de maior tempo de incubação, o grupo contendo NaF demostrou os melhores resultados. Na analise de CTX, houve diferença significante em relação aos inibidores (F46,543, p<0,0001), pH (F=14,836, p<0,0004) e tempo de incubação (F=161,438, p<0,0001) com significante interação entre esses critérios, como ocorrido na perda de massa, não houve diferença estatística nos períodos de menor incubação. No período de maior tempo de incubação, mais uma vez o grupo NaF mostrou os melhores resultados. No valor acumulado de CTX, os grupos E64 e controle negativo tiveram os maiores valores de CTX acumulado, o grupo NaF, independente do pH mostrou redução significante em relação aos demais grupos. Após analise dos resultados dos dois subprojetos, podemos indicar que as MMPs são as proteases de maior importância na progressão da erosão dentinária, assim, sua inibição é de maior importância para a redução desta patologia. Mesmo as CCs não exercendo papel direto para a progressão da erosão, elas são efetivas na cascata da ativação de outras proteases, como as próprias MMPs. Com isso, sua inibição também pode ser importante para a redução indireta da progressão da erosão. Neste presente estudo, pudemos comprovar que o NaF tem potencial inibitório sobre as CCs dentinárias, assim, sugerindo um novo inbidor de CCs. Com os resultados deste estudo, podemos afirmar que as MMPs são as principais proteases na progressão da erosão dentinária e que o NaF tem potencial inibitório nas CCs dentinárias.(AU)

In the dentine, the demineralized organic matrix has a protector part against the following erosive challenges. Nevertheless, this layer can be degraded by proteases, like the matrix metalloproteinases (MMPS) and cystein cathepsins (CCs). Recently, the use of proteases of the matrix´s inhibitors, emerged as an important preventive tool against the dentinária erosion. However, the exact mechanisms from which the inhibitors of the proteases may prevent the dentin erosion, as much as the kinds of proteases more involved in this process are not completely known yet. Therefore, the general objective of this project was to investigate the part of the two main proteases of the matrix (MMPs and CCs) in the dental erosion. The project was developed in 2 subprojects, with the following objectives: A)Subproject 1: Evaluate the part of the proteases in the progression of the dental erosion; B)subproject 2: To test the NaF inhibitory potencial in the dentin CCs. To accomplish these objectives, human third molar dentin were used for the preparation of the specimens, obtained in the surgery and urgency clinics of FOB-USP (subproject 1) or granted by the University of Oulu (subproject 2). A) Subproject 1: Dentine blocks 4 X 4 X 2 mm) (n=119) were obtained from the roots of the obtained teeth. The specimens were divided in 7 groups according with their treatment. Gels containing inhibitors (E-64, specific cathepsin B inhibitor II, chlorhexidine, galardin NaF, placebo), or without treatment, were produced, applied only one time over the surface and made the erosive challenge (90s, 4x a day for 5 days) and made profilometric analysis. The specimens were incubated in a solution containing collagenase of Clostridium histolyticum type VII for 96 hours and then a second profilometric analysis was made to determine the thickness of the MOD. Two specimens were separated for the electronic microscopy scan analysis. B) Subproject 2: Dentine sticks (6 mm X 2 mm X 1 mm) (n=60) were cut from the medium coronary portion of the teeth and completely demineralized by immersion in EDTA 0,5 M (pH7,4) ifor 30 days and washed in deionized water under constant agitation in 4º C for 72 hours. The specimens were divided in 6 groups (divided by inhibitors: E-64, NaF and negative control, pH 5,5 or 7,2) and incubated in artificial saliva containing their respective inhibitors for 24 hours, 7 days and 21 days; by the end of each period, the specimens were weighted to evaluate the loss of mass and analised the presence of CTX. A)Subproject 1: the loss of demineralized tissue (m, média± SD) was : CHX 8,4±1,7b, Gala 8,6±1,9b, IECB 9,6±1,4a, E64 9,9±1,3a, NaF 9,9±1,7a, P 10,9±2,2a, ST 11,0±1,5a. The loss of demineralized tissue was: CHX 15,4±2,2b, Gala 16,0±1,8b, IECB 17,6±2,4a, E64 17,6±2,0a, NaF 17,3±2,8a, P 19,1±2,1a, ST 18,9±2,4a. The MMP inhibitors reduced significantly the loss of organic matrix and demineralized tissue in comparison with other groups (p<0,05). There was no significant difference found between the thickness of the remaining demineralized organic matrix.(p=0,845). B)Subproject: In the loss of mass, there was a significant difference in relation to the inhibitor (F=20,047, p<0,0001) and incubation time (F=222,462, p<0,0001) with significant interaction between these criteria, in the periods of lesser time of incubation, the loss was similar for all the tested groups, in the period of higher time of incubation, the group containing NaF demonstrated the best results. In the analysis of CTX, there was significant difference in relation the inhibitors (F46,543, p<0,0001), pH (F=14,836, p<0,0004) and time of incubation (F=161,438, p<0,0001)with significant interaction between these criteria, as occurred in the mass loss, there was no statistic difference in the period of lesser incubation. In the period of higher time of incubation, once again, the NaF group demonstrated the best results. The CTX accumulated value, the E64 groups and negative control had the greater accumulated values of CTX, the NaF group, regardlessof the pH, demonstrated significant reduction in relation to the other groups. After the analysisof the results of both subprojects, we can indicate that the MMPs are the proteases of greater importance in the progression of the dentin erosion, thus, its inhibition is of graeter importance for the reduction of this pathology. Even the CCs don´t playing the part directly for the progression of erosion, they are effective in the cascade of the activation of other proteases, like the MMPs themselves. In this manner, its inhibition can also be important for the indirect reduction of the progression of the erosion. In this present study, we can prove that the NaF has inhibiting potential over the dentin CCs, thus, suggesting a new inhibitor of CCs. With the results of this study, we can affirm that the MMPs are the main proteases in the progression of the dentin erosion and that the NaF has inhibiting potential in the dentin CCs.(AU)

The use of sodium trimetaphosphate for matrix metalloproteinase inhibition, remineralization and bonding to dentin / O uso de trimetafosfato de sódio sobre a inibição de metaloproteinases e na remineralização e adesão à dentina

The adhesive process to dentin substrate depends on the condition determined by the combined action of the mineral loss and the endogenous enzymes activity. Thus, considering a more complete therapeutic approach, sodium trimetaphosphate (STMP) may be a novel strategy that conciliates the remineralization potential to the promotion of dentin strengthening and its stability, possibly directing mineral nucleation and controlling the rate of biodegradation. In this study, the effect of STMP was evaluated in 2 studies. In study 1, different concentrations of STMP (0.5, 1.5, 3.5 and 5%) were investigated to assess their anti-proteolytic capacity on human purified MMPs-2 and -9 by zymography. Afterwards, only the concentrations (1.5, 3.5 and 5%) that showed total inhibition of both MMPs were used to evaluate their remineralizing capacity in dentin substrate submitted to artificial cariogenic challenge, through surface hardness (SH) and cross-sectional hardness (CSH). In study 2, based on the previous results, the capacity of the 1.5% STMP associated or not with NaF or Ca(OH)2 solutions in improving the dentin bond strength of a universal adhesive system was evaluated by the microtensile test . Thus, these studies suggest that 1.5% STMP is an effective inhibitor of collagen degradation mediated by purified human MMPs-2 and -9. In addition, demineralized and treated dentin with 1.5% STMP supplemented with Ca(OH)2 may induce remineralization. Thus, the use of STMP can be introduced as a new strategy that combines enzymatic inhibition and remineralization potential, reestablishing favorable conditions to affected dentin. These evidences support perspectives of therapies to restructure dentin and propose feasible and promising clinical strategies.(AU)

O processo adesivo ao substrato dentinário depende da condição determinada pela ação combinada da perda mineral e atividade de enzimas endógenas. Deste modo, considerando uma abordagem terapêutica mais completa, o trimetafosfato de sódio (STMP) pode ser uma estratégia inovadora que concilia o potencial remineralizador à promoção do fortalecimento da dentina e sua estabilidade, possivelmente direcionando a nucleação mineral e controlando a taxa de biodegradação. Neste trabalho, o efeito do STMP foi avaliado em 2 estudos. No estudo 1, diferentes concentrações de STMP (0,5; 1,5; 3,5 e 5%) foram investigadas para avaliar sua capacidade anti-proteolítica sobre as MMPs-2 e -9 purificadas humanas, por zimografia. Posteriormente, somente as concentrações (1,5; 3,5 e 5%) que apresentaram capacidade de inibição total de ambas MMPs foram utilizadas para avaliar sua capacidade remineralizadora em substrato dentinário submetido ao desafio cariogênico artificial, através da dureza de superfície (DS) e longitudinal (DL). No estudo 2, baseado nos resultados anteriores, foi avaliada a capacidade do STMP à 1,5% associado ou não a soluções de NaF ou Ca(OH)2 em melhorar a resistência de união à dentina de um sistema adesivo universal pelo teste de microtração. Desta forma, estes estudos sugerem que o STMP à 1,5% apresenta-se como um inibidor eficaz da degradação do colágeno mediada por MMPs-2 e -9 humanas purificadas. Além disso, a dentina humana desmineralizada e tratada com STMP à 1,5% suplementada com Ca(OH)2 pode induzir à remineralização. Assim, o uso de STMP pode ser introduzido como uma nova estratégia que combina inibição enzimática e potencial de remineralização, reestabelecendo condições favoráveis a partir de uma dentina afetada. Estas evidências sustentam perspectivas de terapias para reestruturar a dentina e propor estratégias clínicas factíveis e promissoras.(AU)

Evaluación de fluoruro residual en saliva después de la aplicación de barnices fluorados al 2.26 por ciento: estudio comparativo / An evaluation of the residual fluoride in saliva after applying 2.26 per cent fluoride varnishes: a comparative study

El objetivo de este estudio fue comparar la cantidad de fluoruro (F) residual en saliva después de la aplicación de barniz de fluoruro desodio al 5 por ciento y de barniz fluorado con fosfato tricálcico al 5 por ciento en niños de 2 a 5 años de edad. Se recolectó la saliva no estimulada de 24 niños que tenían acceso a sal fluorada diariamente y utilizaban dentífricos infantiles conteniendo 550 ppm F. La primera toma de muestrasalival fue colectada como basal y las siguientes fueron tomadas en diferentes intervalos de tiempo luego de realizar la aplicación del barnizfluorado (15; 30; 60 minutos y 24; 48; 72; 96; 168 horas). Un total de 216 muestras fueron obtenidas, siendo 96 muestras de barniz de Duraphat®, 96 muestras de barniz de ClinproTM WV y 24 muestras muestras basales. Los análisis de laboratorio fueron realizadosen el departamento de Bioquímica de la Facultad de Odontología de Baurú (FOB), Universidad de Sao Paulo. Un electrodo Orión 9409 y un microelectrodo acoplados a un potenciómetro Orion EA 940 se utilizaron para analizar las muestras previa difusión de las muestrascon el método de Taves. La concentración de iones de flúor mostró diferencias estadísticamente significativas entre ambos productos desde las 24 horas (p<0.001), esta característica se repite a las 48 (p=0.003); 96 (p<0.001) y 168 horas (p<0.001). Se utilizó el análisisestadístico de Shapiro Wilks y T de Student. Ambos barnices mostraron un incremento de fluoruro residual en saliva durante los 15; 30 y 60 minutos, sin embargo, posteriormente a estos tiempos, ambos muestran niveles no significativamente diferentes al basal.

The aim of this study was compared the amount of residual fluoride after application of sodium fluoride varnish 5% and application offluoride varnish with phosphate tricalcium 5% in children from 2 to 5 years old. Unstimulated saliva was collected of 24 children who hadaccess to fluoridate salt daily and used children´s tooth pastes containing 550ppm F. The first salivary sample was collected as a base lineand the following were taken at different intervals after making the application of fluoride varnish (15; 30; 60 minutes; 24; 48; 72; 96;168 hours).Children were grouped in two groups according of type of varnish containing fluoride going to be applied. A total of 216samples were obtained, 96 samples from Duraphat® and 96 samples from ClinproTM WV 3M ESPE. The lab analyzes wereconducted in the Department of Biochemistry at the Faculty of Dentistry, Bauru (FOB), University of Sao Paulo. An Orion 9409electrode and a microelectrode coupled to a potentiometer Orion EA 940 analyzed the samples prior dissemination of samples with themethod of work. The fluoride concentration was statistically significant after 24 (p<0.001); 48 (p=0.003); 96 (p<0.001) y 168 hours(p<0.001) for both products. We used Shapiro Wilks and T student test for statistical analysis. Both products showed an increased inresidual fluoride in saliva during the 15; 30 and 60 minutes, however, both showed not differences that baseline levels.