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Selective inhibition of cyclooxygenase (COX)-2 enzyme is an important achievement when looking for potent anti-inflammatory agents, with fewer gastrointestinal side effects. In this work, a new series of cinnamic acid derivatives, namely hexylamides, have been designed, synthesized and evaluated in human blood for their inhibitory activity of COX-1 and COX-2 enzymes. From this, new structure-activity relationships were built, showing that phenolic hydroxyl groups are essential for both COX-1 and COX-2 inhibition. Furthermore, the presence of bulky hydrophobic di-tert-butyl groups in the phenyl ring strongly contributes for selective COX-2 inhibition. In addition, a correlation with the theoretical log P has been carried out, showing that lipophilicity is particularly important for COX-2 inhibition. Further, a plasma protein binding (PPB) prediction has been performed revealing that PPB seems to have no influence in the activity of the studied compounds. From the whole study, effective selective inhibitors of COX-2 were found, namely compound 9 (IC 50  = 3.0 ± 0.3 μM), 10 (IC 50  = 2.4 ± 0.6 μM) and 23 (IC 50  = 1.09 ± 0.09 μM). Those can be considered starting point hit compounds for further optimization as potential non-steroidal anti-inflammatory drugs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fuel and lubricating oil leaks produce an oily wastewater that creates an environmental problem for industries. Dissolved air flotation (DAF) has been successfully employed for the separation of oily contaminants. Collectors constitute an auxiliary tool in the DAF process that enhances the separation efficiency by facilitating the adhesion of the contaminant particles. The use of biosurfactants as collectors is a promising technology in flotation processes, as these biomolecules are biodegradable and non-toxic. In the present study, a biosurfactant was produced from the bacteria Pseudomonas aeruginosa UCP 0992 cultivated in 0.5% corn steep liquor and 4.0% vegetable oil residue in a bioreactor at 225 rpm for 120 h, resulting in a surface tension of 26.5 mN/m and a yield of 26 g/L. The biosurfactant demonstrated stability when exposed to different temperatures, heating times, pH values and salt and was characterised as a glycolipid with a critical micelle concentration of 600 mg/L. A central composite rotatable design was used to evaluate the effect of the crude biosurfactant added to a laboratory DAF prototype on the removal efficiency of motor oil. The isolated and formulated forms of the biosurfactant were also tested in the prototype after the optimisation of the operational conditions. The results demonstrated that all forms of the biosurfactant increased the oil separation efficiency of the DAF process by 65 to 95%. In conclusion, the use of biosurfactants is a promising alternative as an auxiliary tool in flotation processes for the treatment of oily waters generated by industrial activities.

C-6α and C-7α androstanes were studied to disclose which position among them is more convenient to functionalize to reach superior aromatase inhibition. In the first series, the study of C-6 versus C-7 methyl derivatives led to the very active compound 9 with IC 50 of 0.06 μM and K i = 0.025 μM (competitive inhibition). In the second series, the study of C-6 versus C-7 allyl derivatives led to the best aromatase inhibitor 13 of this work with IC 50 of 0.055 μM and K i = 0.0225 μM (irreversible inhibition). Beyond these findings, it was concluded that position C-6α is better to functionalize than C-7α, except when there is a C-4 substituent simultaneously. In addition, the methyl group was the best substituent, followed by the allyl group and next by the hydroxyl group. To rationalize the structure-activity relationship of the best inhibitor 13, molecular modeling studies were carried out.

The need to remediate areas contaminated by petroleum products has led to the development of novel technologies for treating such contaminants in a non-conventional manner, that is, without the use of chemical or physical methods. Biosurfactants are amphipathic biomolecules produced by microorganisms that can be used in bioremediation processes in environments contaminated by petroleum products due to their excellent tensioactive properties. The aim of the present study was to produce a biosurfactant from Pseudomonas aeruginosa UCP 0992 cultivated in 0.5% corn steep liquor and 4.0% vegetable oil residue in a 1.2-L bioreactor employing a central composite rotatable design to optimize the cultivation conditions for maximum yield. The best results were achieved with aeration rate of 1.0 vvm and 3.0% inoculum at 225 rpm for 120 h, resulting in a surface tension of 26.5 mN/m and a biosurfactant yield of 26 g/L. Kinetic and static assays were then performed with the biosurfactant for the removal of motor oil adsorbed to sand, with removal rates around 90% and 80%, respectively, after 24 h. Oil degradation experiments with the bacterium and the combination of the bacterium and biosurfactant were also conducted to simulate the bioremediation process in sand and seawater samples (duration: 75 and 30 days, respectively). In both cases, oil degradation rates were higher than 90% in the presence of the biosurfactant and the producing species, indicating the potential of the biomolecule as an adjuvant in petroleum decontamination processes in the marine environment., (Copyright © 2018. Published by Elsevier B.V.)

The aim of the present study was to investigate the separation of oil from water using a bench-scale DAF prototype with the addition of biosurfactants isolated from Pseudomonas cepacia CCT6659 and Bacillus cereus UCP1615. The best operating conditions for the DAF prototype were determined using a central composite rotatable design. The results demonstrated that the biosurfactants from P. cepacia and B. cereus increased the oil separation efficiency from 53.74% (using only microbubbles) to 94.11 and 80.01%, respectively. The prediction models for both DAF-biosurfactant systems were validated, showing an increase in the efficiency of the DAF process from 53.74% to 98.55 and 70.87% using the formulated biosurfactants from P. cepacia and B. cereus, respectively. The biosurfactant from P. cepacia was selected as the more promising product and used for the treatment of oily effluent from a thermoelectric plant, achieving removal rates ranging between 75.74 (isolated biosurfactant) and 95.70% (formulated biosurfactant), respectively.

The multiplicity of new therapies for breast cancer presents a challenge for treatment selection. We describe a 17-gene digital signature of breast circulating tumor cell (CTC)-derived transcripts enriched from blood, enabling high-sensitivity early monitoring of response. In a prospective cohort of localized breast cancer, an elevated CTC score after three cycles of neoadjuvant therapy is associated with residual disease at surgery ( P = 0.047). In a second prospective cohort with metastatic breast cancer, baseline CTC score correlates with overall survival ( P = 0.02), as does persistent CTC signal after 4 weeks of treatment ( P = 0.01). In the subset with estrogen receptor (ER)-positive disease, failure to suppress ER signaling within CTCs after 3 weeks of endocrine therapy predicts early progression ( P = 0.008). Drug-refractory ER signaling within CTCs overlaps partially with presence of ESR1 mutations, pointing to diverse mechanisms of acquired endocrine drug resistance. Thus, CTC-derived digital RNA signatures enable noninvasive pharmacodynamic measurements to inform therapy in breast cancer. Significance: Digital analysis of RNA from CTCs interrogates treatment responses of both localized and metastatic breast cancer. Quantifying CTC-derived ER signaling during treatment identifies patients failing to respond to ER suppression despite having functional ESR1. Thus, noninvasive scoring of CTC-RNA signatures may help guide therapeutic choices in localized and advanced breast cancer. Cancer Discov; 8(10); 1286-99. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1195 ., (©2018 American Association for Cancer Research.)

Aim: Considering the epidemiology of leishmaniasis, the emergence of resistant parasites to the approved drugs, and severe clinical manifestations, the development of novel leishmanicidal molecules has become of considerable importance., Results: In this work, three commercially available and 19 synthesized quinoline derivatives were evaluated against promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. In addition, structural parameters and molecular electrostatic potentials were obtained by theoretical calculations, allowing statistical (principal component analyses and hierarchical cluster analyses) and comparative (molecular electrostatic potentials vs leishmanicidal activities) studies, respectively., Conclusion: Principal component analyses and hierarchical cluster analyses suggested volume and polar surface area as possible structural descriptors for the leishmanicidal activity. Furthermore, a comparison between molecular electrostatic potentials and leishmanicidal activities afforded a reasonable structure-activity relationship.

Background: Topotecan (TPT) is a water-soluble derivate of camptothecin, which undergoes ring-opening hydrolysis in neutral solutions, leading to stability loss and poor cellular uptake. Lipid nanoencapsulation can improve TPT stability, and polymer-lipid hybrid nanoparticles (PLN) are interesting alternatives to improve TPT nanoencapsulation., Objective: This study seeks to prepare complexes between the cationic TPT and the negatively charged dextran sulfate (DS) with a view of improving drug loading, chemical stability and release control., Methods: The optimum ionic molar ratio in DS-TPT complexation was determined, and the selected complex was characterized by FTIR and solid-state 13C NMR. TPT solubility in the free and complexed forms was also assayed. TPT-PLN was then obtained via a microemulsion technique, and particle size, zeta potential, encapsulation efficiency, drug loading and drug recovery were determined. Additionally, the TPT stability and in vitro release were determined from PLN and compared with free TPT, TPT-DS complex and TPT encapsulated in nanostructured lipid carriers (NLC) of similar composition., Results: TPT-DS complexation was confirmed by FTIR and NMR. TPT solubility in the complex was drastically decreased when compared to free TPT. TPT-PLN had high encapsulation efficiency (97%) and drug loading capacity (5.5%). Additionally, TPT-PLN showed a mean diameter, polidispersivity index e zeta potential of 140 nm, 0.2 and -22 mV, respectively. The TPT chemical stability and release from PLN were observed to be superior when compared to NLC., Conclusion: PLN has shown to be a more effective nanosystem for TPT nanoencapsulation because TPT loading, stability and release were superior when compared to TPT-NLC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The majority of breast cancer cases are estrogen receptor positive (ER + ). Although, third-generation aromatase inhibitors (AIs) are used as first-line treatment in post-menopausal women, they cause endocrine resistance and bone loss, which limits their success. Therefore, there is a demand to discover new potent molecules, with less toxicity that can circumvent these drawbacks. Our group has previously demonstrated that new 7α-substituted steroidal molecules, 7α-(2ξ,3ξ-epoxypropyl)androsta-1,4-diene-3,17-dione (3), 7α-allylandrost-4-ene-3,17-dione (6), 7α-allylandrost-4-en-17-one (9), 7α-allyl-3-oxoandrosta-1,4-dien-17β-ol (10) and 7α-allylandrosta-1,4-diene-3,17-dione (12) are potent AIs in placental microsomes. In this work, it was investigated their anti-aromatase activity and in vitro effects in sensitive and resistant breast cancer cells. All the steroids efficiently inhibit aromatase in breast cancer cells, allowing to establish new structure-activity relationships for this class of compounds. Moreover, the new AIs can inhibit breast cancer cell growth, by causing cell cycle arrest and apoptosis. The effects of AIs 3 and 12 on sensitive cells were dependent on aromatase inhibition and androgen receptor (AR), while for AI 9 and AI 10 were AR- and ER-dependent, respectively. In addition, it was shown that all the AIs can sensitize resistant cancer cells being their behavior similar to the sensitive cells. In summary, this study contributes to the understanding of the structural modifications in steroidal scaffold that are translated into better aromatase inhibition and anti-tumor properties, providing important information for the rational design/synthesis of more effective AIs. In addition, allowed the discovery of new potent 7α-substituted androstane molecules to inhibit tumor growth and prevent endocrine resistance., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: To evaluate, using a novel micro-CT approach, the solubility and dimensional changes of an MTA-based sealer inside the root canal system after a solubility challenge. The MTA-based material (MTA Fillapex) was compared to a gold standard epoxy-based endodontic sealer (AH Plus)., Methodology: Ten human mandibular premolars with a single canal were divided randomly into two groups (n = 5) according to the sealer used. The canals were instrumented using the Reciproc System (VDW) with a R40 file and filled with R40 gutta-percha cones and one of the sealers. The filled canals were immediately scanned in a micro-CT, and after that, the teeth were immersed in 20 mL phosphate-buffered saline (PBS) at 37 °C for 7 days, when they were removed and rescanned. Final image stacks were registered against the initial stacks and the numerical difference between the initial and final volume of the filling material was obtained. Calculations were performed to identify dimensional changes of the filling material. All image stacks were 3D rendered to disclose areas of dislocation of the filling material inside or outside the root canal. The Shapiro-Wilk's test revealed that data were normally distributed; thus, the Student's t-test was used to detect statistically significant changes, assuming a 5% α-error., Results: No significant changes were seen for the percentage volume of material lost after the solubility challenge for both AH Plus and MTA Fillapex groups (1.44% and 1.16%, respectively). A significant difference was, however, found for the volume of filling material which revealed dimensional changes after the solubility test (6.68% for MTA Fillapex and 1.09% for AH Plus). In fact, observation of 3D models disclosed that MTA Fillapex was associated with material extrusion through the foramen in all but one sample. In AH Plus filled samples, no material extrusion was detected., Conclusions: Although the solubility of both sealers was similar using this novel micro-CT approach, MTA Fillapex was associated with significant dimensional changes related to material extrusion through the apex after PBS storage compared to AH Plus., (© 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Introduction: The aim of the present study was to evaluate the percentage frequency of dentinal micro-cracks observed after root canal preparation with TRUShape and Self-Adjusting File (SAF) systems by means of micro-computed tomography imaging analysis. A conventional full-sequence rotary system (BioRace) and a single-file reciprocation system (Reciproc) were used as reference techniques for comparison because of their known assertive cutting efficiency., Methods: Forty anatomically matched mandibular incisors were selected, scanned at a resolution of 14.25 μm, and assigned to 4 experimental groups (n = 10), according to the preparation protocol: TRUShape, SAF, BioRace, and Reciproc systems. After the experimental procedures, the specimens were scanned again, and the registered preoperative and postoperative cross-section images of the roots (n = 70,030) were screened to identify the presence of dentinal micro-cracks., Results: Overall, dentinal defects were observed in 28,790 cross-section images (41.11%). In the TRUShape, SAF, BioRace, and Reciproc groups, dentinal micro-cracks were visualized in 56.47% (n = 9842), 42.38% (n = 7450), 32.90% (n = 5826), and 32.77% (n = 5672) of the slices, respectively. All dentinal defects observed in the postoperative data sets were already present in the corresponding preoperative images., Conclusions: None of the preparation systems induced the formation of new dentinal micro-cracks., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of the present study was to evaluate the influence of Blue thermal treatment on the bending resistance and cyclic fatigue of conventional M-Wire Reciproc files (VDW, Munich, Germany). The roughness pattern and the microhardness of the files were also assessed., Methods: Flexibility of standard Reciproc R25 files and the corresponding Blue prototypes was determined by 45° bending tests according to the ISO 3630-1 specification. Instruments were also subjected to cyclic fatigue resistance, measuring the time to fracture in an artificial stainless steel canal with a 60° angle and a 5-mm radius of curvature. The fracture surface of all fragments was examined with a scanning electron microscope. The roughness of the working parts was quantified by using a profilometer, and the microhardness test was performed using the Vickers hardness tester. Results were statistically analyzed using the Student t test with a level of significance set at P < .05., Results: Reciproc Blue instruments presented a significantly longer cyclic fatigue life and significantly lower bending resistance than the original Reciproc instrument (P < .05). Regarding the roughness pattern, there was no significant difference between Reciproc Blue and the original Reciproc instruments (P > .05), whereas Reciproc Blue revealed significantly lower microhardness than the original Reciproc instrument (P < .05)., Conclusions: Reciproc Blue nickel-titanium showed improved all-around performance when compared with conventional M-Wire superelastic nickel-titanium, demonstrating improved flexibility and fatigue resistance, and reduced microhardness while maintaining similar characteristics of the surface., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

In this work, the potential of ouricuri (Syagrus coronata) fiber as a novel biosorbent to remove methylene blue (MB) from aqueous solutions was investigated. The fiber was prepared and characterized according to the fundamental features for adsorption. A 2 3 experimental design was used to evaluate the effects of adsorbent dosage (M), fiber diameter (D) and agitation (A) on the adsorption capacity. In the more adequate conditions, kinetic and equilibrium studies were performed. The experimental design results showed that M = 10 g L -1 ), D = 0.595 mm and A = 200 rpm were the more adequate conditions for MB adsorption. Based on the kinetic study, it was found that the adsorption process was fast, being the equilibrium was attained at about 5 min, with 90% of color removal. The isotherm was properly represented by the Sips model, and the maximum adsorption capacity was 31.7 mg g -1 . In brief, it was demonstrated that ouricuri fiber is an alternative biosorbent to remove MB from aqueous media, taking into account the process efficiency and economic viewpoint.

The ever-increasing demand for natural products and biotechnology derived from bees and ultra-modernization of various analytical devices has facilitated the rational and planned development of biotechnology products with a focus on human health to treat chronic and neglected diseases. The aim of the present study was to prepare and characterize polymeric nanoparticles loaded with Brazilian red propolis extract and evaluate the cytotoxic activity of "multiple-constituent extract in co-delivery system" for antileishmanial therapies. The polymeric nanoparticles loaded with red propolis extract were prepared with a combination of poly-ε-caprolactone and pluronic using nanoprecipitation method and characterized by different analytical techniques, antioxidant and leishmanicidal assay. The red propolis nanoparticles in aqueous medium presented particle size (200-280 nm) in nanometric scale and zeta analysis (-20 to -26 mV) revealed stability of the nanoparticles without aggregation phenomenon during 1 month. After freeze-drying method using cryoprotectant (sodium starch glycolate), it was possible to observe particles with smooth and spherical shape and apparent size of 200 to 400 nm. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and thermal analysis revealed the encapsulation of the flavonoids from the red propolis extract into the polymeric matrix. Ultra performance liquid chromatography coupled with diode array detector (UPLC-DAD) identified the flavonoids liquiritigenin, pinobanksin, isoliquiritigenin, formononetin and biochanin A in ethanolic extract of propolis (EEP) and nanoparticles of red propolis extract (NRPE). The efficiency of encapsulation was determinate, and median values (75.0 %) were calculated using UPLC-DAD. 2,2-Diphenyl-1-picryhydrazyl method showed antioxidant activity to EEP and red propolis nanoparticles. Compared to negative control, EEP and NRPE exhibited leishmanicidal activity with an IC50 value of ≅38.0 μg/mL and 31.3 μg/mL, 47.2 μg/mL, 154.2μg/mL and 193.2 μg/mL for NRPE A1, NRPE A2, NRPE A3 and NRPE A4, respectively. Nanoparticles loaded with red propolis extract in co-delivery system and EEP presented cytotoxic activity on Leishmania (V.) braziliensis. Red propolis extract loaded in nanoparticles has shown to be potential candidates as intermediate products for preparation of various pharmaceutical dosage forms containing red propolis extract in the therapy against negligible diseases such as leishmaniasis. Graphical Abstract Some biochemical mechanisms of cellular debridement of Leishmania (V.) braziliensis species by the flavonoids of red propolis extract (EEP) or NRPE loaded with red propolis extract.

Introduction: This study evaluated the bending resistance and cyclic fatigue life of a new single-file reciprocating instrument (Unicone; Medin, Nové Město na Moravě, Czech Republic). Reciproc (VDW, Munich, Germany) and WaveOne (Dentsply Maillefer) instruments were used as references for comparison., Methods: Flexibility was determined by 45° bending tests using a universal testing machine. The cyclic fatigue test was performed using a custom-made device. For this test, an artificial canal with a 60° angle and a 5-mm radius of curvature was used. Scanning electron microscopic analysis was performed to determine the mode of fracture and possible deformations at the helical shaft. Statistical analysis for the bending resistance test was performed using parametric methods (ie, 1-way analysis of variance). Post hoc pair-wise comparisons were performed using the Tukey test for multiple comparisons (P < .05). Weibull analysis was used to calculate the mean life, beta, and eta parameters., Results: Reciproc presented significantly lower bending resistance than the other tested systems (P < .05), whereas no differences were observed between WaveOne and Unicone (P > .05). When mean life was compared among the brands, Reciproc lasted longer than WaveOne with a probability of 99.9%, longer than Unicone in the "RECIPROC ALL" mode with a probability of 99.9%, and longer than Unicone in the "WAVEONE ALL" mode with a probability of 99.9% (all statistically significant). Moreover, WaveOne lasted longer than Unicone in the "RECIPROC ALL" mode with a probability of 98.5% and longer than Unicone in the "WAVEONE ALL" mode with a probability of 99.8% (all statistically significant). Finally, Unicone in the "RECIPROC ALL" mode lasted longer than Unicone in the "WAVEONE ALL" mode with a probability of 95.3% (statistically significant)., Conclusions: The new reciprocating instrument Unicone showed lower cyclic fatigue resistance compared with Reciproc R25 and WaveOne Primary files., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The current study aimed to evaluate the bending resistance and the cyclic fatigue life of a new heat-treated reciprocating instrument (ProDesign R). Untreated ProDesign R, Reciproc R25, and WaveOne Primary instruments were used as reference instruments for comparison. The bending resistance was performed in ten instruments of each system by using a universal testing machine and a proper apparatus. The cyclic fatigue resistance was tested measuring the number of cycles to failure in an artificial stainless steel canal. Scanning electron microscopy analysis was performed to determine the mode of fracture and possible deformations at the helical shaft. Statistical analysis was performed by using parametric methods; one-way analysis of variance plus post hoc pair-wise Tukey test for multiple comparisons (p < 0.05). Untreated ProDesign R presented significantly higher bending resistance than the other tested systems (p < 0.05). No differences were observed between ProDesign R and Reciproc files regarding the bending resistance (p > 0.05). Moreover, ProDesign R revealed a significantly longer cyclic fatigue life (p < 0.05). In contrast, Untreated ProDesign R and WaveOne instruments presented significantly lower cyclic fatigue life than Reciproc (p < 0.05). The new heat-treated reciprocating instrument ProDesign R have higher cyclic fatigue resistance than Untreated ProDesign R, Reciproc, and WaveOne instruments. ProDesign R and Reciproc were significantly more flexible than Untreated ProDesign R and WaveOne files. SCANNING 38:837-841, 2016. © 2016 Wiley Periodicals, Inc., (© Wiley Periodicals, Inc.)

Introduction: The present study aimed to rank the bond strength to root dentin of a new injectable pozzolan-based root canal sealer, EndoSeal MTA, as compared with MTA Fillapex and AH Plus., Methods: Eighteen dentinal slices (1 ± 0.1 mm) were obtained from the middle third of 6 maxillary incisors previously selected. Three canal-like holes with 0.8 mm diameter were drilled perpendicularly on the axial surface of each slice. Then, a standardized irrigation was applied for all holes that were subsequently filled with 1 of 3 test root canal sealers. After that, slices were stored in contact with phosphate-buffered saline solution (pH 7.2) for 7 days at 37°C before the push-out assay. Friedman test and Wilcoxon signed rank test with a Bonferroni correction were used to rank the results. Significance boundary was set at α = 5%., Results: Friedman test confirmed a significant dissimilarity in push-out ranks among the tested cements (P < .01). Wilcoxon signed rank test demonstrated AH Plus had significant superior resistance to dislodgment compared with Endo Seal (P < .01) or MTA Fillapex (P < .01), whereas MTA Fillapex presented the lowest push-out values as compared with Endo Seal (P < .01) or AH Plus (P < .01)., Conclusions: EndoSeal presents satisfactory bond strength performance for application in endodontic therapy compared with MTA Fillapex, and although it displays a new alternative of injectable bio-tight root canal sealer, it is not able to improve adhesion compared with AH Plus., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

This study aimed to evaluate the cause-effect relationship between canal preparation with ProTaper Universal (PTU) system and dentinal defects formation using micro-computed tomography (micro-CT) analysis. Forty mesial canals of mandibular molars with a type II Vertucci's canal configuration were scanned at an isotropic resolution of 14.16 µm. The sample was assigned to an experimental (n = 30) and a control (n = 10) groups, and the mesial canals were prepared with PTU system up to F2 instrument. The specimens from the experimental group were scanned and the cross-section images of the mesial roots, before and after preparation, were screened to identify the presence of dentinal defects. In the control group, the specimens were sectioned perpendicularly to the long axis of the root into 1-mm-thick slices (n = 80) and examined under optical microscope. Once a dentinal defect was detected, the slice was scanned through micro-CT. In the experimental group, dentinal micro-cracks were observed in 4,828 slices (24.04%). In all cross-section images, dentinal defects identified in the postoperative images were already present in the corresponding preoperative image. In the control group, 13 out of 80 slices (16.25%) had at least one dentinal defect visualized under stereomicroscopy, which was identified after a further micro-CT scanning. Micro-CT showed reliability as similar as optical microscopy in detecting dentinal defects, adding the possibility of tracking the dentinal tissue, before and after canal preparation, and providing a clear visualization of micro-cracks. Root canal preparation with PTU system did not induce the formation of new dentinal defects.

Introduction: Glide path preparation has been recommended as a mandatory clinical step to ensure the safe usage of nickel-titanium (NiTi) rotary instruments. This study aimed to evaluate the effectiveness and fracture rate of 4 pathfinding NiTi rotary instruments in mechanically negotiating moderately curved molar canals., Methods: Moderately curved maxillary (n = 120) and mandibular (n = 120) molars were randomly distributed into 4 experimental groups (n = 60, 30 maxillary and 30 mandibular molars) according to the instrument used for glide path preparation: ScoutRace 10/.02 (FKG Dentaire, La Chaux-de-Fonds, Switzerland) (800 rpm and 1-Ncm torque), ProDesign 25/.01 (Easy Equipamentos Odontológicos, Belo Horizonte, MG, Brazil) (350 rpm and 1-Ncm torque), Mtwo 10/.04 (VDW, Munich, Germany) (280 rpm and 1.2 Ncm torque), or ProGlider 16/.02 (Dentsply Maillefer, Ballaigues, Switzerland) (300 rpm and 5-Ncm torque). The instrument fracture rate and the absolute and percentage frequencies of molars in which the pathfinding instruments reached the full working length in all root canals according to tooth and canal types were recorded and statistically compared using the Pearson's chi-square test (α = 5%)., Results: The highest and lowest frequency of reached the full working length canals were observed in the ScoutRace (68.3%) and ProDesign (38.3%) groups (P < .05), respectively, whereas the Mtwo (58.3%) and ProGlider (51.6%) groups showed intermediate results (P > .05). The ProGlider group showed the highest percentage frequency of instrument separation (11.6%) followed by the Mtwo (8.3%), ScoutRace (3.3%), and ProDesign (3.3%) groups (P < .05)., Conclusions: ScoutRace performed more efficiently and with less instrument breakage than the other systems. ProDesign was the least efficient, and ProGlider exhibited the highest rate of instrument breakage among the systems tested., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The aim of the present study was to evaluate the cytotoxic effects of five endodontic sealers (AH Plus, Endomethasone N, EndoSequence BC, MTA Fillapex and Pulp Canal Sealer EWT) using a three-dimensional (3D) cell culture model. A conventional bi-dimensional (2D) cell culture model was used as reference technique for comparison. Balb/c 3T3 fibroblasts were cultured in conventional bi-dimensional cell culture and in rat-tail collagen type I three-dimensional cell culture models. Then, both cell cultures were incubated with elutes of freshly mixed endodontic sealers for 24 h. Cell viability was measured by the methyl-thiazol-diphenyltetrazolium assay (MTT). Data were statistically analyzed using ANOVA and the Tukey test at a significance level of p<0.05. All tested sealers exhibited cytotoxic effects; however, cytotoxic effect was culture model- and sealer-dependent. Sealers showed higher cytotoxicity in 2D than in 3D cell culture model (p<0.05). In both conditions, EndoSequence BC showed the lowest cytotoxicity (p<0.05). MTA Fillapex was much more cytotoxic than the other tested endodontic sealers (p<0.05), with the exception of AH Plus in the 2D cell culture model (p>0.05). Endomethasone N and Pulp Canal Sealer EWT showed lower cytotoxic effects than AH Plus in 2D cell culture model (p<0.05); however no statistical differences was observed among these sealers in 3D cell culture model. It may be concluded that cytotoxicity was higher in 2D cell culture compared to 3D cell culture. EndoSequence BC sealer exhibited the highest cytocompatibility and MTA Fillapex the lowest cytocompatibility.

Colon cancer is one of the most incident cancers in the Western World. While both genetic and epigenetic factors may contribute to the development of colon cancer, it is known that chronic inflammation associated to excessive production of reactive oxygen and nitrogen species by phagocytes may ultimately initiate the multistep process of colon cancer development. Phenolic compounds, which reveal antioxidant and antiproliferative activities in colon cancer cells, can be a good approach to surpass this problem. In this work, hydroxycinnamic amides and the respective acid precursors were tested in vitro for their capacity to modulate human neutrophils' oxidative burst and simultaneously to inhibit growth of colon cancer cells. A phenolic amide derivative, caffeic acid hexylamide (CAHA) (4) was found to be the most active compound in both assays, inhibiting human neutrophils' oxidative burst, restraining the inflammatory process, inhibiting growth of colon cancer cells and triggering mitochondrial dysfunction that leads cancer cells to apoptosis. Altogether, these achievements can contribute to the understanding of the relationship between antioxidant and anticancer activities and based on the structure-activity relationships (SAR) established can be the starting point to find more effective phenolic compounds as anticancer agents., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: To evaluate and compare the push-out bond strength of MTA Fillapex (Angelus, Londrina, Brazil) and iRoot SP (Innovative BioCeramix Inc., Vancouver, Canada) to the dentine walls of root canals. AH Plus (Dentsply DeTrey, Konstaz, Germany) and MTA (Angelus, Londrina, Brazil) were used as reference materials., Methodology: Sixty extracted human single-rooted teeth were selected. After standardized canal preparation and irrigation, the canals were dried with paper points and filled with one of four sealers: AH Plus, iRoot SP, MTA and MTA Fillapex. Roots were sectioned, and push-out tests were performed. The values of bond strength were analysed using the Kruskal-Wallis test. Mann-Whitney with Bonferroni correction was used to isolate the differences. The alpha-type error was set at 0.05 for the analyses., Results: All specimens had measurable adhesion to root dentine and no premature failure occurred. There were significant differences amongst materials (P = 0.000). MTA-filled specimens had higher push-out bond strength values (P = 0.000). AH Plus had significantly higher bond strength than both Fillapex and iRoot SP (P = 0.000). Both Fillapex and iRoot SP had the lowest push-out bond strength amongst all experimental groups (P = 0.000). No difference occurred between the two calcium silicate-based root canal sealers (P = 0.265)., Conclusion: The adhesion to root dentine associated with newer calcium silicate-based sealers was compromised even when well-monitored laboratory conditions were used., (© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Aim: To evaluate the amount of apically extruded debris produced by ProTaper Universal (PTU), ProTaper Next (PTN), WaveOne (WO) and Reciproc (R) systems after large apical preparations., Methodology: Sixty mandibular premolars with a single canal were selected and randomly assigned into 4 groups (n = 15) according to the system used for root canal preparation: PTU, PTN, WO and R groups. Canal preparations were performed up to size 40 in each group. Distilled water was used as an irrigant, and the apically extruded debris from each tooth was collected in pre-weighted glass vials and dried. The average weight of debris was assessed using a microbalance, and the data were analysed statistically using one-way analysis of variance and the post hoc Tukey multiple comparison test (α = 0.05)., Results: The PTU system was associated with significantly more debris than the other systems (P < 0.05). No significant differences were found between PTN, WO and R systems (P > 0.05)., Conclusions: All systems were associated with apical debris extrusion when canals were prepared to a large apical size. The PTU system was associated with more debris extrusion., (© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Many studies have focused on the search for a restorative material with good sealing properties and biocompatibility for treatment of teeth with open apices and necrotic pulps, which can result from periradicular disease and root resorption. Mineral trioxide aggregate (MTA) has exhibited promising clinical results in retrograde fillings and pulpotomies as well as for treatment of root perforations, root resorptions, incomplete root formations, and pulpal necrosis. This case report describes the management of a progressive apical root resorption in a previously traumatized tooth that had been endodontically treated. Five years of clinical and radiographic follow-up demonstrated the clinical efficacy of MTA in limiting the inflammatory resorptive process and promoting apexification and regeneration of periradicular tissue.

The aim of the present study was to verify the long-term cytotoxic effects of the MTA Fillapex and to compare them with AH Plus. Dissolution rate and pH were also evaluated. Human osteoblast cells were incubated with elutes of fresh specimens from AH Plus and MTA Fillapex, and with elutes of the same specimens for 4 successive weeks. Elute's pH was evaluated at each time point. A multiparametric cell viability assay was performed. For dissolution rate, ISO methodology was used. The results were analyzed by one-way analysis of variance, complemented with the Tukey post-test (p<0.05). No significant difference was found among the materials when fresh mixed (p>0.05). After 1 week, AH Plus became non-cytotoxic on all three evaluated parameters. Conversely, MTA Fillapex remained severely and mildly cytotoxic over the entire experimental period (p<0.05). The dissolution rate of AH Plus was significantly lower than MTA Fillapex at all time points (p>0.05). The pH of AH Plus was significantly lower than MTA Fillapex at the second and third week (p<0.05). In the other tested time points no statistical difference was observed. In conclusion, MTA Fillapex remained cytotoxic after 4 weeks and its cytotoxicity may be related to the high dissolution rate of this material.

In this work, new potent steroidal aromatase inhibitors both in microsomes and in breast cancer cells have been found. The synthesis of the 3,4-(ethylenedioxy)androsta-3,5-dien-17-one (12), a new steroid containing a heterocycle dioxene fused in the A-ring, led to the discovery of a new reaction for which a mechanism is proposed. New structure-activity relationships were established. Some 5β-steroids, such as compound 4β,5β-epoxyandrostan-17-one (9), showed aromatase inhibitory activity, because they adopt a similar A-ring conformation as those of androstenedione, the natural substrate of aromatase. Moreover, new chemical features to increase planarity were disclosed, specifically the 3α,4α-cyclopropane ring, as in 3α,4α-methylen-5α-androstan-17-one (5) (IC50=0.11μM), and the Δ(9-11) double bond in the C-ring, as in androsta-4,9(11)-diene-3,17-dione (13) (IC50=0.25μM). In addition, induced-fit docking (IFD) simulations and site of metabolism (SoM) predictions helped to explain the recognition of new potent steroidal aromatase inhibitors within the enzyme. These insights can be valuable tools for the understanding of the molecular recognition process by the aromatase and for the future design of new steroidal inhibitors., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This study was designed to investigate the resistance to dislodgment provided by MTA HP, a new high-plasticity calcium silicate-based cement. Biodentine and White MTA Angelus were used as reference materials for comparison. Three discs 1 ± 0.1 mm thick were obtained from the middle third of the roots of 5 maxillary canines. Three 0.8-mm-wide holes were drilled on the axial surface of each root disc. Standardized irrigation was performed. Then the holes were dried with paper points and filled with one of the three tested cements. The filled dental slices were immersed in a phosphate-buffered saline (PBS) solution (pH 7.2) for 7 days before the push-out assessment. The Kruskal-Wallis test was applied to assess the effect of each endodontic cement on the push-out bond strength. Mann-Whitney with Bonferroni correction was used to isolate the differences. The alpha-type error was set at 0.05. All specimens had measurable push-out values and no premature failure occurred. There were significant differences among the materials (p <0.05). The Biodentine specimens had the highest push-out bond strength values (p < 0.05). MTA HP had significantly higher bond strength than White MTA (p < 0.05). MTA HP showed better push-out bond strength than its predecessor, White MTA; however, Biodentine had higher dislodgment resistance than both MTA formulations.

Aim: To evaluate the cytotoxic effects of Biodentine, using a three-dimensional (3D) cell culture associated with an in situ root-end filling experimental model. White mineral trioxide aggregate (MTA) and zinc oxide cement were used as reference for comparison. IL-1α and TNF-α cytokine production were also evaluated., Methodology: The root canals of 24 human maxillary incisor teeth were prepared using a single-file reciprocating technique. After root filling, a 3-mm root-end resection was performed and 3 mm of gutta-percha was removed from the canal. The teeth were randomly distributed to receive one of the following root-end filling materials: Biodentine, white MTA or zinc oxide cement (positive control group). In the negative control group, the root canal was not retro-filled. The cytocompatibility of the materials was evaluated using the methyl-thiazol-diphenyl-tetrazolium (MTT) assay in an in situ root-end filling experimental model. Balb/c 3T3 fibroblasts, cultured in rat tail collagen type I 3D scaffold, were exposed to the root apex for 24 h, and cell viability was measured by means of reduction MTT salt. IL-1α and TNF-α production were analysed using enzyme-linked immunosorbent assay. One-way analysis of variance was performed and, when the F-ratios were significant, data were compared by Duncan's multiple-range test. The alpha-type error was set at 0.05., Results: Biodentine and MTA groups had similar cell activity to the negative control group (P > 0.05), indicating low cytotoxicity for both materials. The stronger cytotoxicity effect was identified on the zinc oxide cement (P < 0.05). Zinc oxide cement caused a significant up-regulation in IL-1α and TNF-α (P < 0.05). No significant differences amongst MTA, Biodentine and the negative control group were observed for TNF-α (P > 0.05); however, both MTA and Biodentine were associated with overproduction of IL-1α when compared to the control group (P < 0.05)., Conclusions: Biodentine and MTA had similar cytocompatibility in a 3D cell culture model associated with an in situ root-end filling model. The methodology could be used as an alternative to assess the cytocompatibility of endodontic cements because it is more closely related to the in vivo situation., (© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Aim: To evaluate the potential for electromagnetic interference (EMI) of electronic apex locators (EALs) and a gutta-percha heating device (HD) in patients with implantable cardiac pacemakers (ICPs) or cardioverter-defibrillators (ICDs)., Methodology: Two types of EALs (Romiapex A-15 and Novapex) and a HD (Touch'n Heat) were tested in patients followed in an outpatient clinic for cardiac arrhythmias. The heart rhythm was monitored on a computer screen during all experimental phases. After baseline data collection, the patient held each appliance (turned on) for 30 s, simulating their clinical use. If background noise was detected on the cardiac monitor, the sensitivity of the ICP/ICD was lowered by the cardiologist to evaluate the intensity of the detected EMI., Results: Twelve patients were evaluated (5 female and 7 male), and in nine instances, background noise in their cardiac devices related to the use of the endodontic devices was detected (6 patients). After lowering the sensitivity of the cardiac implants, three patients had more severe EMI in six instances, including pauses in ICP function. The presence of a symptomatic or asymptomatic pause was related to the patient's underlying heart rhythm. The HD device produced background noise more often compared to EALs. These were associated with more severe types of EMI., Conclusion: The EALs and gutta-percha HD were capable of causing background noise detection or pauses in cardiac implants in vivo. The use of electronic dental devices nearby patients with cardiac implants should be carefully considered in clinical practice., (© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Aim: Line pairs are the unit for measurement of resolution and are related to the spatial quality of the system. Thus, the objective of this study was to evaluate the influence of number of line pairs in digital intra-oral radiography on the detection accuracy of horizontal root fractures., Materials and Methods: Sixty-four extracted single-root human teeth were used. Thirty-two had horizontal root fractures created and were mounted in dry human mandibles. The teeth were radiographed with two digital receptors: the Digora Optime (14.3 lp mm-1) and the Digora Toto (26.3 lp mm-1). Images were viewed under standardized conditions by 3 calibrated examiners using the respective dedicated software (Digora for Windows 2.6(®) and Scanora(®) ). Digora Toto(®) images were also evaluated through the Digora for Windows 2.6(®) software. The results were statistically analyzed based on the area under the ROC curve for each examiner., Results: Pairing Digora Toto(®) with Scanora(®) allowed for greater accuracy in horizontal root fractures diagnosis, while images acquired with that same system seem to lose accuracy when visualized with Digora for Windows 2.6(®) . Pairing Digora Optime(®) with Digora for Windows 2.6(®) resulted in the lowest accuracy for horizontal root fractures diagnosis., Conclusions: The higher number of line pairs and the consequent higher image resolution provided by the Digora Toto(®) system and its dedicated software seem to enhance the accuracy of horizontal root fractures diagnostic imaging., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Lower urinary tract dysfunction (LUTD) are voiding dysfunctions without anatomical or neurological defects. The diagnosis is primarily clinical, with symptoms standardized by the International Children's Continence Society. Few studies relate quality of life of patients with cognitive and school performance., Objective: To evaluate milestones of bladder control, daily problems, quality of life (QoL), cognitive function and school performance of children with LUTD., Methods: Case series of patients followed in the Pediatric Nephrology tertiary hospital with assessment of QoL (Pediatric Quality of Life Inventory - PedsQoL version 4), School Performance Test (TDE) and Raven Progressive Matrices test., Results: Girls of lower social class were (90.9%) of eligible children. The mean age was 9.1 ± 4.8 years old. The most common symptoms were urge incontinence (81%), holding maneuvers (77.3%) and enuresis (59.1%) associated with the elimination disorder syndrome (63.6%). Caregivers considered volunteers urinary losses and/ or symptoms, and fought and/or beat the child. Children had been subjected to embarrassing situations such as warnings of teachers, they hid symptoms and/or the dirty clothes. Mean score of QoL was 71.0 ± 12.6 with the lowest mean score on the school dimension. In TDE 55% had lower performance and in Raven Matrices 60% were intellectually in the medium level. It was observed lower QoL scores in the medium and lower level of TDE and average intellectual capacity/below average in Raven matrices., Conclusion: LUTD may negatively affect family and social relationships, school performance and QoL of children with the dysfunction.

β-defensins are components of host defense, with antimicrobial and pleiotropic immuno-modulatory properties. Research over the last 15 years has demonstrated abundant expression of a variety of β-defensins in the postnatal epididymis of different species. A gradient of region- and cell-specific expression of these proteins is observed in the epithelium of the postnatal epididymis. Their secretion into the luminal fluid and binding to spermatozoa as they travel along the epididymis has suggested their involvement in reproduction-specific tasks. Therefore, continuous attention has been given to various β-defensins for their role in sperm function and fertility. Although β-defensins are largely dependent on androgens, the underlying mechanisms regulating their expression and function in the epididymis are not well understood. Recent investigation has pointed out to a new and interesting scenario where β-defensins emerge with a different expression pattern in the Wolffian duct, the embryonic precursor of the epididymis, as opposed to the adult epididymis, thereby redefining the concept concerning the multifunctional roles of β-defensins in the developing epididymis. In this review, we summarize some current views of β-defensins in the epididymis highlighting our most recent data and speculations on their role in the developing epididymis during the prenatal-to-postnatal transition, bringing attention to the many unanswered questions in this research area that may contribute to a better understanding of epididymal biology and male fertility.

Objectives: The purpose of this study was to assess the ability of ProTaper Gold (PTG, Dentsply Maillefer) in maintaining the original profile of root canal anatomy. For that, ProTaper Universal (PTU, Dentsply Maillefer) was used as reference techniques for comparison., Materials and Methods: Twenty simulated curved canals manufactured in clear resin blocks were randomly assigned to 2 groups (n = 10) according to the system used for canal instrumentation: PTU and PTG groups, upto F2 files (25/0.08). Color stereomicroscopic images from each block were taken exactly at the same position before and after instrumentation. All image processing and data analysis were performed with an open source program (FIJI). Evaluation of canal transportation was obtained for two independent canal regions: straight and curved levels. Student's t test was used with a cut-off for significance set at α = 5%., Results: Instrumentation systems significantly influenced canal transportation (p < 0.0001). A significant interaction between instrumentation system and root canal level (p < 0.0001) was found. PTU and PTG systems produced similar canal transportation at the straight part, while PTG system resulted in lower canal transportation than PTU system at the curved part. Canal transportation was higher at the curved canal portion (p < 0.0001)., Conclusions: PTG system produced overall less canal transportation in the curved portion when compared to PTU system.

We evaluated the cytotoxic effects of the debris apically extruded during root canal retreatment on primary human osteoblast (HOb) cells in vitro. TNF-α and IL-1β levels were also measured. We examined three different techniques: conventional hand-files, and Mtwo and Reciproc retreatments. Filled mandibular incisors were prepared for a cytotoxicity assay in an experimental root model. The material was divided into three groups according to the technique used. Ten teeth were used as control. HOb cells were exposed to the extruded content and cytotoxicity was evaluated using the MTT test (assessing cell metabolic activity). TNF-α and IL-1β production was also analyzed using enzyme-linked immunosorbent assay. Then, all the teeth were radiographed and the residual filling material was quantified. Data were subjected to analysis of variance (ANOVA) and Tukey's test (P < 0.05). The conventional hand-file technique was significantly more cytotoxic than the other methods (P < 0.05). Reciproc was less cytotoxic than Mtwo retreatment (P < 0.05). All endodontic retreatment techniques led to a significant upregulation of IL-1β levels (P < 0.05). However, only the conventional hand-file technique caused a significant increase in TNF-α levels (P < 0.05). Root-filling removal did not affect the levels of these proteins (P > 0.05). The Reciproc system required less time than the other two methods to remove the root-filling materials (P < 0.01). The endodontic retreatment with Reciproc was the least cytotoxic and the least time-consuming method of gutta-percha and sealer removal. (J Oral Sci 58, 211-217, 2016).

The aim of the present study was to prospectively assess the frequency of teeth in which the Reciproc instruments were able to reach the full working length (WL). This case series study enrolled 277 consecutive teeth requiring primary endodontic treatment performed with the Reciproc system (VDW) without a previous glide path by 3 experienced endodontists. Instruments R25, R40 or R50 were selected, respectively, for narrow, medium and large canals, according to the preoperative radiographs, as per manufacturer recommendation. Canals were instrumented and classified as reaching the full WL (RFWL) and not reaching the full WL (NRFWL), according to the ability of the Reciproc instrument to reach without a glide path the full electronically determined WL. Finally, canals were filled using a single matched cone technique. Pearson's squared-chi test compared the frequency distributions of canals classified as RFWL and NRFWL. From a total pool of 673 root canals, Reciproc instruments reached the FWL in 96.28% of cases and 3 fractures occurred. For narrow canals the percentage of RFWL was 95.37% with 3 fractures. For medium and large canals, the R40 or R50 instruments reached the FWL in 98.51% and 97.62% of the cases respectively, with no fracture. Enlarging of root canals using the Reciproc instruments up to the FWL without a glide path is successful in a great percentage of cases. This case series suggests the possibility of using a single instrument to enlarge the root canal space of teeth by a simpler approach without an a prioriglide path procedure.

Purpose: To investigate the resistance to dislodgment produced by Biodentine (Septodont) and White-MTA (Angelus) after immersion in phosphate-buffered saline (PBS) for different durations., Materials and Methods: Dentin disks 1 ± 0.1 mm thick were obtained from the middle third of the roots of 6 human maxillary canines. On the coronal surface of each dentin disk, four 0.8-mm-diameter holes were drilled. Then the slices were halved using a low-speed saw diamond disk, and the two holes in each half were filled with one of the two tested materials. Each filled half was immersed in PBS solution (pH 7.2) either for 7 days (short term) or 60 days (long term) at 37°C. The push-out test was performed after both time periods. A general linear model (GLM) for repeated measures ANOVA was used to verify the effect of the material and duration of contact with PBS on the push-out strength. The material was considered as the within-subject contrast and the contact duration as the between-subjects effect (p < 0.05)., Results: Repeated measures GLM indicated a significant impact of material and time on the push-out strength of the samples (p = 0.000 and p = 0.033, respectively). Biodentine significantly improved the push-out strength compared to MTA at both times (p = 0.000). The lack of significance in the interaction between material and time indicates that PBS immersion positively influenced the push-out values of both tested materials., Conclusion: Long-term PBS immersion positively influenced the resistance to dislodgement from dentin of all cements tested. The Biodentine cement provided greater resistance to push-out force than did the MTA.

The purpose of this study was to assess the ability of an off-centered rectangular design system [ProTaper Next (PTN)] to maintain the original profile of the root canal anatomy. To this end, ProTaper Universal (PTU), Reciproc (R) and WaveOne (WO) systems were used as reference techniques for comparison. Forty clear resin blocks with simulated curved root canals were randomly assigned to 4 groups (n = 10) according to the instrumentation system used: PTN, PTU, R and WO. Color stereomicroscopic images of each block were taken before and after instrumentation. All image processing and data analysis were performed with an open source program (Fiji v.1.47n). Evaluation of canal transportation was obtained for two independent regions: straight and curved portions. Univariate analysis of variance and Tukey's Honestly Significant Difference test were performed, and a cut-off for significance was set at α = 5%. Instrumentation systems significantly influenced canal transportation (p = 0.000). Overall, R induced significantly lower canal transportation compared with WO, PTN and PTU (p = 0.000). The curved portion displayed superior canal transportation compared to the straight one (p = 0.000). The significance of the difference among instrumentation systems varied according to the canal level evaluated (p = 0.000). In its straight portion, R and WO exhibited significantly lower transportation than PTN; whereas in the curved portion, R produced the lowest deviation. PTU exhibited the highest canal transportation at both levels. It can be concluded that PTN produced less canal transportation than PTU and WO; however, R exhibited better centering ability than PTN.

Objective: Several studies demonstrate variability of root canal morphology of anterior teeth. This in-vivo study was designed to analyze and characterize root canal morphology of maxillary and mandibular anterior teeth using three-dimensional imaging., Method and Materials: Patients who required CBCT radiographic examinations as part of their routine examination, diagnosis, and treatment planning were enrolled on the study. A total of 1,200 healthy, untreated, fully developed maxillary and mandibular incisors and canines were included. The following observations were recorded: (i) number of roots and their morphology; (ii) number of canals per root; and (iii) primary variations in the morphology of the root canal systems., Results: Root canal morphology of maxillary teeth was consistent with a single canal extending from the pulp chamber to the apex in 98% of the cases. In contrast, in mandibular central and lateral incisors, the presence of a single canal represented 64.5% and 60.5% respectively. The second most common morphology was the presence of one canal leaving the pulp chamber, which divided into two within the root, and then merged to exit as one canal in 18% and 25.5% respectively. The presence of one canal leaving the pulp chamber and dividing short of the apex into two separate and distinct canals with separate apical foramina (variant 5) was recorded in 14.5% and 12% respectively., Conclusion: There was a low incidence of anatomical variation in maxillary anterior teeth. In contrast, mandibular anterior teeth presented with a high prevalence of two canals, especially central and lateral incisors. The reported data may help clinicians understand the variations in root canal morphology of anterior teeth in order to overcome problems associated with shaping and cleaning procedures.

The aim of this study was to quantitatively evaluate the amount of apically extruded debris by single-file reciprocating instruments with different working lengths and apical preparation sizes. Eighty human single-rooted mandibular incisors were used and conventional access cavities were prepared. Then, the specimens were divided into four groups (n=20), according to root canal instrumentation: Reciproc size 25, .08 taper and Reciproc size 40, .06 taper instruments were used at the foramen; Reciproc size 25, .08 taper and Reciproc size 40, .06 taper instruments were used 1 mm short of the foramen. Distilled water was used as an irrigant and the apically extruded debris were collected in pre-weighted glass vials and dried afterwards. The mean weight of debris was weighed with a microbalance and statistically analyzed using one-way analysis of variance and the post hoc Tukey multiple comparison test (p<0.05). The results showed that all experimental groups were associated with debris extrusion. No significant difference was found in the amount of apically extruded debris among all experimental groups (p>0.05). The present study demonstrated that the working length and the apical preparation size did not have a significant effect on debris extrusion when performing single-file reciprocating instrumentation.

The aim of this study was to analyze the antimicrobial activity and substantivity of Uncaria tomentosa Willd DC (cat's claw, CC) in root dentin contaminated with Enterococcus faecalis. Forty-eight human premolars were contaminated with E. faecalis (ATCC 29212) and randomly divided into four groups according to the irrigant used during chemomechanical preparation (CMP): CC group: 2% CC gel; CHX group: 2% chlorhexidine digluconate gel (CHX); NaOCl group: 5.25% sodium hypochlorite (NaOCl); and SS group: sterile saline (SS). Microbiological samples were collected before (S1) and after (S2) CMP and after 7 days (S3). Colony-forming units (CFU/mL) at the different sampling times and comparisons among the groups were statistically analyzed by Wilcoxon and Kruskal-Wallis tests (p < 0.05). Significant bacterial reduction was achieved in all groups after CMP (p < 0.05). Results show no significant difference between S3 and S2 (p > 0.05) in the CC and CHX groups. Bacterial load was higher in S3 than in S2 samples (p < 0.05) in the NaOCl and SS groups. Our results suggest antibacterial effect of 2% CC gel against E. faecalis in infected dentin, in addition to antibacterial substantivity of 2% CC and 2% CHX up to 7 days.

Aim: The present study evaluated the influence of the working length and foraminal enlargement on the sealing ability and anatomy of the apical region of the root., Materials and Methods: Fifty-five roots were divided into three groups: G1, instrumentation 1 mm short of the major foramen; G2, instrumentation in the limit of the apical foramen; and G3, instrumentation 1 mm beyond the foramen. All groups were prepared using nickel-titanium rotary files and obturated with AH Plus and Gutta-percha. Photomicrographs were taken using a scanning electron microscopy (SEM) before instrumentation, after instrumentation with each file, and after root canal filling. Moreover, bacterial microleakage with Enterococcus faecalis was performed., Results: The results were analyzed using Mann-Whitney, Friedman, Kruskal-Wallis and Kaplan-Meier tests at a significance level of 5%. The cemental canal was uninstrumented in G1. No statistical differences regarding foramen deviation was observed when compared G2 and G3 (P > 0.05). SEM analysis showed that G2 and G3 resulted in good apical foramen obturation. Microleakage showed no statistically significant differences between all of the groups tested., Conclusions: Under the conditions of this study, it can be concluded that foramen enlargement resulted in more apical deviation; however, no differences in bacterial microleakage was observed among the experimental groups.

Developing a non-hormonal male contraceptive requires identifying and characterizing an appropriate target and demonstrating its essential role in reproduction. Here we review the development of male contraceptive targets and the current therapeutic agents under consideration. In addition, the development of EPPIN as a target for contraception is reviewed. EPPIN is a well characterized surface protein on human spermatozoa that has an essential function in primate reproduction. EPPIN is discussed as an example of target development, testing in non-human primates, and the search for small organic compounds that mimic contraceptive antibodies; binding EPPIN and blocking sperm motility. Although many hurdles remain before the success of a non-hormonal male contraceptive, continued persistence should yield a marketable product., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To compare the cytotoxicity, gelatinolytic activity, and protein levels (MMP-2 and MMP-9) produced by 3T3 fibroblasts cells after stimulation with GuttaFlow 2 and AH Plus., Methods: 3T3 fibroblasts were incubated with elutes of GuttaFlow 2 and AH Plus for 24 h. The cytotoxicity of tested materials was determined using the MTT and the LDH assay. Supernatants of cell cultures incubated with sealers were collected to determine the levels of MMP-2 and MMP-9 gelatinolytic activity by gelatin zymography. Cell lysates were used to determine MMP-2 and MMP-9 protein levels by Western Blot. Data were analyzed using ANOVA and Tukey test (P&lt;0.05)., Results: AH Plus showed significantly less cell viability (mitochondrial activity of cells) than GuttaFlow 2 (P&lt;0.01). Moreover, GuttaFlow 2 was noncytotoxic, showing no statistically significant difference in LDH leakage levels compared to the control group (P&gt;0.05). Specific characterization of MMPs demonstrated that GuttaFlow 2 seemed not to affect MMP-2 levels compared with the control group, while AH Plus had elevated gelatinolytic activity and protein levels of MMP-2 as confirmed by quantitative measurements. No detectable gelatinolytic activity or protein levels of MMP-9 (92 kDa) was observed in any tested group., Conclusions: GuttaFlow 2 did not showed cytotoxic effects and did not induce MMP-2 or MMP-9 expression.

Aim: To investigate endotoxin levels from primary endodontic infections before and after chemomechanical preparation (CMP) and to determine their antigenicity against 3T3 fibroblasts through gelatinolytic activity of matrix metalloproteinases (MMPs)., Methodology: Twenty-four root canals with primary endodontic infection and apical periodontitis were selected. Samples were collected using paper points before (S1) and after chemomechanical preparation (CMP) (S2). The limulus amebocyte lysate assay was used for endotoxin measurement. Fibroblasts were stimulated with root canal contents for 24 h. Supernatants of cell cultures stimulated with root canal contents were collected after 24 h to determine the levels of MMP-2 and MMP-9 gelatinolytic activity using the zymography technique. Friedman and Wilcoxon tests were used to compare the amount of endotoxin before (S1) and after CMP (S2) (P < 0.05). Data obtained from gelatinolytic activity were analysed using anova and Tukey's tests (P < 0.05)., Results: Endotoxin was recovered in 100% of the samples. There was a significant reduction in endotoxin levels after CMP (P < 0.05). A correlation was found between the levels of endotoxins and MMP-2 expression (P < 0.05). Root canal contents of initial samples (S1) induced significantly greater MMP-2 expression by fibroblasts when compared to S2 and the nonstimulated group (P < 0.05). No gelatinolytic activity of MMP-9 was observed in S1, S2 and control group., Conclusions: Root canal contents from primary endodontic infections had gelatinolytic activity for MMP-2. Moreover, CMP was effective in reducing endotoxin levels and their antigenicity against fibroblasts on gelatinolytic activity., (© 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

The aim of the present study was to compare the porosity characteristics of AH Plus Jet(tm) syringe-mix and the conventional hand-mixed AH Plus root canal sealers by three-dimensional quantitative high-resolution micro-computed tomography (micro-CT). Seven test specimens were prepared from each tested sealer by a single operator following the manufacturer's instructions and poured into pre-lubricated plastic split-ring moulds. Set sealer test specimens were scanned using a micro-CT device and the shadow images were reconstructed into cross-sectional slices. The evaluated parameters were (i) total pore count, (ii) total pore volume and mean pore volume, (iii) total porosity (% of pore volume in relation to total sealer volume) and (iv) mean pore distance to the sealer lateral external surface. In both groups, most pores were localized within the external sealer perimeter (0.05 mm from the external surface). Hand-mixed AH Plus specimens showed statistically significant higher mean total pore count, total pore volume and total porosity (p=0.001) than the syringe-mixed specimens. However, mean pore sizes in AH Plus syringe-mixed specimens were significantly higher (p=0.046) than the AH Plus hand-mixed counterparts. Hand-mixed AH Plus was associated with higher total mean pore count, volume and total porosity compared to syringe mixed AH Plus.

The aim of this study was to compare the percentage of non-instrumented area of root canals prepared with different enlargements using single-file reciprocating systems (Reciproc and WaveOne) and a conventional multi-file rotary (BioRaCe) system by micro-computed tomographic analysis. Thirty mesial roots of mandibular molars with moderate curvature (10° to 20°) presenting a type II Vertucci canal configuration and similar internal volume were chosen and scanned at an isotropic resolution of 14.16 µm. The sample was assigned to 3 groups (n=10) according to the system used for root canal preparation: Reciproc, WaveOne, and BioRaCe groups. Second and third scans were taken after the canals were prepared with instruments sizes 25 and 40, respectively. The recorded images of the surface area voxels of the canals, before and after preparation were examined from the furcation level to the apex to quantify the non-instrumented surface. Statistical data were compared using GLM for repeated-measures with a significance level set at 5%. Instrumentation systems did not influence the percentage of untouched root canal surfaces (p=0.690) whilst a significant reduction in the percentage of static voxels was observed after the enlargement of the root canal (p=0.010) in all groups (p=0.507). None of the systems was able to prepare the entire surface area of the mesial root canal of mandibular molars. The increased final apical size resulted in a significant positive effect on the shaping ability of the tested systems.