Mentha spp. essential oils: toxicity to Alphitobius diaperinus, activity against poultry pathogenic bacteria, and Beauveria bassiana compatibility.

The botanical insecticide market is growing because of limitations placed on the use of certain synthetic chemical insecticides. In this sense, the lesser mealworm Alphitobius diaperius (Coleoptera: Tenebrionidae) is the main poultry pest. The insect causes weight loss and damage to the digestive system of poultry, and it is a vector and reservoir of pathogens. Consequently, this study explored the following hypotheses: (i) essential oils (EOs) derived from Mentha spp. are toxic to A. diaperius; (ii) these EOs are compatible with Beauveria bassiana, the natural enemy of the poultry pest, that parasite A. diaperinus; (iii) these EOs also exhibit activity against bacteria that are pathogenic to poultry. In topical applications and ingestion tests, EOs from Mentha arvensis, Mentha spicata, and Mentha piperita were toxic to A. diaperinus. Chromatographic analyses revealed that menthol is the predominant compound in M. arvensis and M. piperita, whereas carvone is the major compound in M. spicata. Both (-)- and (+)-menthol, along with (-)- and (+)-carvone, underwent testing with A. diaperinus. Nevertheless, their activity was not as potent as those of the EOs, suggesting a possible synergistic and/or additive effect. The EOs did not have any adverse effects on the conidial germination, vegetative growth, or conidia production per colony of the entomopathogenic fungus B. bassiana. Consequently, these EOs are compatible with this natural enemy. The EO extracted from M. spicata exhibited significant toxicity against Staphylococcus aureus (ATCC 25923), whereas the remaining EOs displayed moderate toxicity against this bacterium. The EOs derived from Mentha spp., as assessed in this study, hold promise for the development of botanical insecticides tailored for the control of A. diaperinus. These insecticides are selective in favor of the natural enemy B. bassiana and can also serve as effective sanitizers, thanks to their antibacterial properties.

Validação biológica de grânulos de vidro bioativas (compostos por biovidro 45S5): estudo in vitro e in vivo / Biological validation of bioactive glass granules (composed of 45S5 bioglass): in vitro and in vivo study

O tecido ósseo, embora tenha a capacidade de regeneração, é limitado em sua eficácia diante de defeitos críticos que impedem a regeneração natural. Dessa forma, materiais como a hidroxiapatita (HA) têm sido considerados promissores na engenharia de tecido ósseo. Contudo, apesar de sua ampla utilização, a hidroxiapatita apresenta desvantagens, como a taxa de reabsorção e remodelação lenta. Em contraste, o biovidro 45S5 se destaca por sua biocompatibilidade, propriedades bioativas e degradabilidade. Este estudo objetivou avaliar o comportamento biológico in vitro e in vivo de grânulos de vidro bioativas de biovidro 45S5 fabricadas pelo método de fusão. Os biovidros foram caracterizados por meio da difração de raios X (DRX), espectroscopia de infravermelho por transformação de Fourier (FTIR), calorimetria diferencial de varredura (DSC) e espectrometria de emissão óptica com plasmas indutivamente acoplados (ICP OES). Em seguida, foi realizado o estudo in vitro, utilizando células osteoblásticas isoladas de fêmures de ratos, que foram submetidas a análise da morfologia celular (MEV), viabilidade celular (MTT), conteúdo de proteína total (PT), atividade de fosfatase alcalina (ALP) e formação de nódulos de mineralização. No estudo in vivo, foram realizados defeitos ósseos críticos de 7 mm na tíbia de coelhos da raça New Zealand, que foram divididos em dois grupos (n=6) de acordo com o material de preenchimento: hidroxiapatita comercial (HA) e biovidro 45S5 (BG45S5). Após 2, 8 e 12 semanas, os animais foram eutanasiados e as peças ósseas foram submetidas as análises histológicas e histomorfométricas. Os dados foram submetidos ao teste de normalidade Shapiro-Wilk (p=0,05) e quando normais realizamos o teste t de student e quando não normais realizamos o teste de Mann-Whitney. Os resultados dos testes físico-químicos mostraram sucesso na produção do novo biomaterial. Nos testes in vitro, observou-se que o grupo BG45S5 não apresentou citotoxicidade e mostrou-se promissor com diferença estatisticamente significante em relação ao grupo hidroxiapatita comercial (p=0.0263). Nos testes de PT, ALP e nódulos de mineralização, os grupos não apresentaram diferença estatística entre eles (p<0,05). Contudo, o grupo BG45S5 mostrou-se promissor em relação aos outros grupos. Na análise histológica, ambos os grupos apresentaram neoformação óssea nos defeitos após 2, 8 e 12 semanas. Na histomorfometria, observou-se que os grupos BG45S5 e HA apresentaram maior área de neoformação óssea em 12 semanas. Houve diferença estatisticamente significante entre os grupos no tempo de 2 semanas, com maior neoformação para o grupo BG45S5. Apesar dos resultados promissores do grupo BG45S5, não houve diferença estatisticamente significativa entre os grupos (p<0,05) nos tempos de 8 e 12 semanas. Em resumo, os resultados evidenciaram o sucesso na produção do biomaterial sintético e o potencial do biomaterial BG45S5 como um material promissor para tratamento de defeitos ósseos críticos. (AU)

Bone tissue, despite its capacity of regeneration, is limited in its effectiveness when faced with critical defects that prevent natural regeneration. Therefore, materials such as hydroxyapatite (HA) have been considered promising in bone tissue engineering. However, despite its wide use, hydroxyapatite has disadvantages, such as slow resorption and remodeling rates. In contrast, 45S5 bioglass stands out for its biocompatibility, bioactive properties and degradability. This study aimed to evaluate the in vitro and in vivo biological behavior of bioactive 45S5 bioglass beads manufactured by the melt quenched method. The bioglasses were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and inductively coupled plasma optical emission spectrometry (ICP OES). Following this, an in vitro study was conducted using osteoblastic cells isolated from rat femurs, which were subjected to analysis of cell morphology (SEM), cell viability (MTT), total protein content (TP), alkaline phosphatase activity (ALP) and mineralization nodule formation. In the in vivo study, critical bone defects of 7 mm were created in the tibia of New Zealand rabbits, which were divided into two groups (n=6) according to the filling material: commercial hydroxyapatite (HA) and bioactive glass 45S5 (BG45S5). After 2, 8, and 12 weeks, the animals were euthanized and the bone pieces were subjected to histological and histomorphometric analyses. Data were subjected to the Shapiro-Wilk normality test (p=0.05), and when normal, we performed the Student's t-test, and when non-normal, we performed the Mann-Whitney test. The results of the physicochemical tests showed success in the production of the new biomaterial. In the in vitro tests, it was observed that the BG45S5 group did not present cytotoxicity and showed promise with a statistically significant difference compared to the commercial hydroxyapatite group (p=0.0263). In the TP, ALP and mineralization nodule tests, the groups showed no statistical difference between them (p<0.05). However, the BG45S5 group showed promise compared to the other groups. In the histological analysis, both groups showed new bone formation in the defects after 2, 8, and 12 weeks. In the histomorphometric analysis, it was observed that the BG45S5 and HA groups presented a larger area of new bone formation at 12 weeks. There was a statistically significant difference between the groups at 2 weeks, with greater new formation for the BG45S5 group. Despite the promising results of the BG45S5 group, there was no statistically significant difference between the groups (p<0.05) at 8 and 12 weeks. In summary, the results evidenced the successful production of the synthetic biomaterial and the potential of the BG45S5 bioglass as a promising material for treating critical bone defect.(AU)

Experimental pastes containing niobophosphate and 45S5 bioactive glasses for treatment of dentin hypersensitivity: dentin permeability and tubule obliteration.

OBJECTIVES: This study tested the ability of bioactive pastes containing niobophosphate and 45S5 glasses to reduce dentin permeability and to obliterate dentinal tubules, as a mean of reducing human dentin hypersensitivity. MATERIALS AND METHODS: Experimental pastes with concentrations of 10, 20, and 30 wt% of two bioactive glasses (45S5 or niobophosphate [NbG]) were formulated. A paste without bioactive glass (placebo) and a commercial paste (Nano P, FGM) were used as controls. Forty dentin disc specimens were obtained from caries-free extracted third human molars and divided in 8 groups (n = 5). Percentage of permeability (%Lp) was assessed in a dental permeability machine considering hydraulic conductance, immediately after pastes application and at day 7, day 14, and day 21. The precipitates formed on the surface of the dentin discs (and dentinal tubules) were analyzed by SEM/EDS and micro-Raman spectra. Data of dentin permeability (%) 2-way repeated-measures (ANOVA) and Holm-Sidak post-tests (α = 0.05). Dentinal tubule obliteration was visually (and elemental) evaluated and descriptively reported. RESULTS: The experimental bioactive glass pastes containing NbG and 45S5, regardless of the concentration, reduced dentin permeability in comparison with pastes without bioactive glasses (P < 0.05). The formulated placebo and commercial paste did not reduce permeability over time (P < 0.05). SEM/EDS and micro-Raman analyses showed that both type of bioactive pastes (NbG or 45S5-based) presented mineral precipitates obliterating the dentinal tubules at day 21. NbG seems to offer a better initial effect than 45S5, while at 21 days there is no difference between both glasses. CONCLUSION: Experimental bioactive pastes containing NbG and 45S5 (at concentrations of 10%, 20%, or 30%) have potential to reduce dentin permeability (over time) in comparison with pastes without bioactive glasses; and this occurs on behalf of obliteration of dentinal tubules by microparticle and precipitate formation. CLINICAL RELEVANCE: Bioactive pastes containing NbG and 45S5 may benefit patients presenting dentin hypersensitivity, because these pastes can start acting fast after application and maintain their action up to 21 days.

Synthesis and characterization of experimental endodontic sealers containing bioactive glasses particles of NbG or 45S5.

OBJECTIVE: This study evaluated the influence of adding bioactive glasses particles [Niobophosphate (NbG) or bioglass (45S5)] into endodontic cements in relation to physical, chemical and biological properties. METHODS: The following commercial cements were used as comparison: AH Plus (Dentsply), Endofill (Dentsply), MTA Fillapex (Angelus) and EndoSequence (BC Sealer, Brasseler). Setting time, radiopacity, flow rate, weight loss/variation, alkaline capacity (pH) at different time-intervals (24h/48h/7d/14d/28d), bioactivity (assessed under SEM/EDS, FTIR/ATR and XDR) and cell viability were measured. Data were analyzed by One-way ANOVA/Holm-Sidak post-test (α = 5%) (normal distribution) and Kruskal-Wallis/Students-Newman-Keuls post-test (α = 5%) (non-normal distribution). RESULTS: Bioactive endodontic experimental cements (containing NbG or 45S5) had high alkalinization capacity. The experimental cements presented high weight loss/variation (p < 0.001). 45S5 experimental cement did not present radiopacity (p < 0.001). AH Plus had the lowest cell cytotoxicity when compared to the other tested cements (p < 0.001). Regarding bioactivity, SEM/EDS analyses showed precipitates with high concentrations of Ca/P for 45S5 and NbG, as well as for MTA Fillapex and BC Sealer. AH plus and Endofill did not present bioactive precipitates. FTIR/ATR and XDR analyses found hydroxyapatite precursors for NbG, 45S5, MTA Fillapex and BC Sealer. SIGNIFICANCE: The incorporation of bioactive particles (NbG or 45S5) into endodontic cements had potential to neutralize acidic environments and induced formation of hydroxyapatite precursors. Clinically, these would produce a cement that is bactericidal and have the potential to improve tissue healing. The improved radiopacity and flowability would facilitate the visualization of the material in the radiograph and the filling of anatomical complexities during root canal obturation. As drawbacks, the excessive weight loss and post-setting cytotoxicity could result in clinical degradation of the cement and adjacent tissue irritation for the patient.

Enamel erosion control by strontium-containing TiO2- and/or MgO-doped phosphate bioactive glass.

OBJECTIVES: To evaluate the effect of strontium-containing titanium- and/or magnesium-doped phosphate bioactive glass on the control of dental erosion. MATERIALS AND METHODS: Fifty fragments of human enamel were divided into five groups: negative control, 45S5 bioglass, strontium-containing Ti-doped phosphate bioactive glass (PBG-Ti), strontium-containing Mg-doped phosphate bioactive glass (PBG-Mg), and strontium-containing Ti- and Mg-doped phosphate bioactive glass (PBG-TiMg). The specimens underwent cycles of erosive challenge twice daily for 5 days with 1 mL of citric acid for 2 min followed by 1 mL of the suspension with bioactive substances for 3 min. After the cycles, profilometry, roughness and microhardness testing, and scanning electron microscopy (SEM) were performed. The following statistical tests were used: one-way ANOVA (profile, roughness, and surface microhardness (%VMS) data variation), Tukey's HSD (%VMS), Games-Howell test (profilometry), Student's t test (roughness), and Pearson's correlation between the variables. RESULTS: The lower loss of enamel surface and lower %VMS was observed in the PBG-Mg and PBG-TiMg groups, and only the PBG-Mg group showed similar roughness between baseline and eroded areas (p > 0.05). On SEM micrographs, PBG-Ti and PBG-Mg groups showed lower apparent demineralization. CONCLUSION: All bioactive materials protected the enamel against erosion. However, strontium-containing phosphate bioactive glasses showed lower enamel loss, and the presence of Mg in these bioactive glasses provided a greater protective effect. CLINICAL RELEVANCE: Experimental strontium-containing phosphate bioactive glasses are effective in controlling enamel erosion. The results obtained in this study will guide the development of new dental products.

Incorporation of 45S5 bioglass via sol-gel in ß-TCP scaffolds: Bioactivity and antimicrobial activity evaluation.

In this work, ß-TCP (ß-tricalcium phosphate) bioresorbable scaffolds were prepared by the gel casting method. Then, they were impregnated with a 45S5 bioglass sol gel solution to improve biocompatibility and promote bioactivity and antimicrobial activity. The ß-TCP scaffolds had an apparent porosity of 72%, and after the incorporation of the bioglass, this porosity was maintained. The elements of the bioglass were incorporated into ß-TCP matrix and there was a partial transformation from the ß-TCP phase to the α-TCP (α-tricalcium phosphate) phase, besides the formation of bioactive calcium and sodium­calcium silicates. The scaffolds ß-TCP with 45S5 bioglass incorporated (ß-TCP/45S5) did not show a reduction in their values of mechanical strength and Weibull modulus, despite the partial transformation to the α-TCP phase. Bioactivity, cell viability, and antimicrobial activity improved significantly for the ß-TCP/45S5 scaffold comparing to the scaffold without the bioglass. The mineralization of carbonated hydroxyapatite was verified in Simulated Body Fluid (SBF). The cell viability, evaluated by the reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide - MTT in MG63 cells, increased by 178%, and ß-TCP/45S5 scaffold also enhanced cell activity and osteoblast differentiation observed by means of total protein contend and alkaline phosphatase activity, respectively. The formation of growth inhibition zones was also observed in the disk diffusion assay for three tested microorganisms: Staphylococcus aureus, Escherichia coli and Candida albicans. To conclude, the vacuum impregnation method in 45S5 bioglass sol gel solution was effective in penetrating all the interconnected macroporosity of the scaffolds and covering the surface of the struts, which improved their biological properties in vitro, bioactivity and antibacterial activity, without reducing mechanical strength and porosity values. Thus, the ß-TCP/45S5 scaffolds are shown as potential candidates for use in tissue engineering, mainly in bone tissue regeneration and recovery.

Biocerámicos: aspectos farmaco-tecnológicos y clínicos de uso odontológico / Bioceramics: pharmatechnological and clinical aspects of dental use

Se analizan aspectos fármaco-tecnológicos y clínicos de biocerámicos bioabsorbibles compuestos por biovidrios con capacidad osteogénica y microbicida, para ser utilizados como relleno bioactivo en el conducto radicular y como tratamiento terapéutico en el sitio de a lesión apicoperirradicular de origen endodóntico. Mediante un diagrama ternario se consideraron las diversas variables cuyos valores determinan las diferentes fases de los vidrios bioactivos, hasta alcanzar la formación de hidroxiapatita, cuando se someten a un medio biológico. Se analizaron composición y mecanismo de acción en la reparación posendodóntica, que parte de la integración del biomaterial al tejido duro sano, sin formación de fibrosis o proceso inflamatorio inmune (AU)

Pharmacotechnological and clinical aspects of bioabsorbable bioceramics composed of bioglasses with osteogenic and microbicidal capacity are analyzed, to be used as a bioactive filler in the root canal and as a therapeutic treatment at the site of an apicoperiradicular lesion of endodontic origin. By means of a ternary diagram, the various variables whose values determine the different phases of the bioactive glasses were considered, until reaching the formation of hydroxyapatite, when subjected to a biological medium. Composition and mechanism of action were analyzed in post-endodontic repair, which starts from the integration of the biomaterial into healthy hard tissue, without the formation of fibrosis or an immune inflammatory process (AU)

Bioglass-based scaffolds coated with silver nanoparticles: Synthesis, processing and antimicrobial activity.

Over the past few years, several tridimensional synthetic bone grafts, known as scaffolds, are being developed to overcome the autologous grafts limitations. Among the materials used on the production of scaffolds, the 45S5 bioglass stands out due to its capacity of bonding to hard and soft tissues. Silver nanoparticles are well-known for their antimicrobial properties and their incorporation on the scaffold may promote its antimicrobial response, avoiding microorganism proliferation on the materials surface. This study proposes a simple way to coat 45S5 bioglass-based scaffolds with silver nanoparticles. The scaffolds were obtained by the sponge replication technique and the silver nanoparticles were incorporated by soaking under ultrasonic stirring. The antimicrobial activity of the scaffolds was analyzed against three different microbial strains: S. aureus, P. aeruginosa, and C. albicans. Due to the heat treatment during the scaffold production, the bioglass crystalized mainly in a sodium calcium silicate phase, forming a glass-ceramic scaffold. The silver nanoparticles were coated in a well-distributed manner throughout the scaffold, while avoiding their aggregation. The coated scaffold inhibited the growth of all the analyzed microorganism. Therefore, the use of ultrasonic stirring to coat the bioglass scaffold with silver nanoparticles showed to be an efficient way to promote its antimicrobial response.

Methylation estimates the risk of precancer in HPV-infected women with discrepant results between cytology and HPV16/18 genotyping.

BACKGROUND: Vigilant management of women with high-risk human papillomavirus (hrHPV) is necessary in cancer screening programs. To this end, we evaluated the performance of S5 (targeting DNA methylation in HPV16, HPV18, HPV31, HPV33, and human gene EPB41L3) to predict cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in a sample of hrHPV-infected women referred to colposcopy in the FRIDA Study, a large screening trial in Mexico. A nested case-control sample with women referred to colposcopy either by atypical squamous cells of undetermined significance or higher (ASCUS+) in cytology and/or positive for HPV types 16 or 18 was tested by S5. Seventy-nine cases of CIN2+ were age-matched to 237 controls without a diagnosis of CIN2+ (

Bioactive glass (45S5)-based 3D scaffolds coated with magnesium and zinc-loaded hydroxyapatite nanoparticles for tissue engineering applications.

Bioactive glass (BG)-based scaffolds of 45S5 composition covered with hydroxyapatite nanoparticles loaded with Mg2+, Zn2+ and, both Mg2+ and Zn2+ ions, were developed and tested as materials for tissue engineering applications. The scaffolds were prepared by the foam replica technique and mono- and bi-metal loaded and unloaded hydroxyapatite nanoparticles (HA, Zn-HA, Mg-HA and Mg-Zn-HA) were obtained by an adaptation of the wet chemical deposition method. Coating of BG with these nanoparticles was performed by dip-coating to obtain HA-BG, Zn-HA-BG, Mg-HA-BG and Mg-Zn-HA-BG scaffolds. As predictor of the bone bonding ability of the produced scaffolds, in this study we investigated the formation of an apatite layer on the scaffold surfaces in the presence of simulated body fluid. The cytotoxicity and osteogenic properties of the materials in vitro was evaluated using human osteoblast-like MG-63 cell cultures. The mineralization assay following Kokubo's protocol indicated that bi-metal loaded Mg-Zn-HA-BG scaffolds exhibited higher/faster bioactivity than mono-metal loaded scaffolds while mineralization of HA-BG, Zn-HA-BG and Mg-HA-BG was similar to that of uncoated scaffolds. Moreover, an increase of proliferation of MG-63 cells after 48 h and 7 days was measured by BrdU assays for Mg-Zn-HA-BG scaffolds. In agreement with these results, SEM images confirmed increased interaction between these scaffolds and cells, in comparison to that observed for mono-metal-loaded HA-coated scaffolds. Altogether, the obtained results suggest that nanocrystalline Mg-Zn-HA coatings enhance the biological performance of standard scaffolds of 45S5 BG composition. Thus these novel ion doped HA coated scaffolds are attractive systems for bone tissue engineering.

Bioglass 45S5: Structural characterization of short range order and analysis of biocompatibility with adipose-derived mesenchymal stromal cells in vitro and in vivo.

Bioactive glasses have potential applications in the field of regenerative medicine due to their bioactivity that permits interaction with both hard and soft tissues. In the same way, mesenchymal stromal cells (MSCs) have been experimentally tested as part of engineered constructs considering their self-renewal and multipotent capacities. However, to design an association, it is crucial to investigate the physical properties of bioglass 45S5, as well as its biocompatibility. Therefore, we investigated the structural short range order of the stoichiometric 45S5, by obtaining its total structure factors (S(K)) and total pair distribution function G(r). The in vitro compatibility of human MSCs with 45S5 was verified by viability, morphometry and osteoinduction assays, F-actin staining and scanning electron (SEM) analysis. The compatibility outcome was verified through a subcutaneous implantation in a murine model by grafting the 45S5 as a scaffold for allogeneic MSCs. The cell-substrate modulation includes the maintenance of the MSC viability and osteoinduction potential after being exposed to the 45S5 extract. A low spreading during cell adhesion was detected. Both normal actin cytoskeleton organization and nuclei irregularities were observed, besides an increase of hydroxyapatite (HA) depositions around cells. Cells showed satisfactory compatibility patterns when growing over 45S5 for 7, 30 and 90 days. The implant did not show any apparent toxicity for organs, or strong immunogenic reactions, and it was accompanied by a dense capsule formation around the graft. Our results indicate that MSCs can grow in the long term on the 45S5 while maintaining their characteristics. This fact, together with a non-toxicity to animals means that the 45S5 can be implemented in pre-clinical trials aiming MSC's transplantation leading to further bone and tissue repair.

Effect of Root Repair Materials and Bioactive Glasses on Microhardness of Dentin.

INTRODUCTION: The use of bioactive glasses to re-establish or increase mechanical properties of the root dentin may be an interesting alternative. The aim of this study was to evaluate the effect of root repair materials and bioactive glasses on the microhardness of human root dentin. METHODS AND MATERIALS: Sixty-four sectioned palatal roots of human molars were prepared and two slices were obtained of the middle third of each root (one corresponding to the control group, without treatment, and the other to the experimental group). The pairs of slices were randomly divided into four groups (n=16). The root canal of experimental slices were filled with one of the following materials: mineral trioxide aggregate (Angelus MTA, Angelus, Londrina, Paraná, Brazil), EndoSequence Root Repair Material (ERRM, Brassler, Savannah, GA, USA), Bioglass (45S5) and an experimental niobophosphate glass (NbG). The specimens were stored in an oven at 37ºC, in an environment with 100% humidity for 60 days. The specimens were subjected to a microhardness test. Four indentations were made at a distance of 20 µm from the root canal lumen. For microhardness analysis, comparing the experimental groups and their respective controls, the Student's-t test was applied. For comparison of the percentage increase in microhardness between the groups, the data were statistically analyzed by using One-way ANOVA and Tukey's test. The level of significance was set at 0.05. RESULTS: All the materials significantly increased the dentin microhardness values (P<0.05). MTA showed a higher increase in microhardness (94.8±42.7%), similar to that of EndoSequence (62.3±39.9%). The 45S5 (46.5±30.0%) and NbG (53.8±31.3%) showed the lowest percentages of increase in microhardness, but were statistically similar to those of EndoSequence. CONCLUSION: All the materials tested were capable of increasing root dentin microhardness.

Functional roles of T3.37 and S5.46 in the activation mechanism of the dopamine D1 receptor.

The activation mechanism of dopamine receptors is unknown. The amino acids S5.42, S5.43, and S5.46 located in helix 5 appear to be crucial, but their specific roles in receptor activation have not been studied. We modeled the D1 dopamine receptor using the crystal structures of the D3 dopamine and ß2 adrenergic receptors. Molecular dynamics simulations show that the interaction of dopamine with the D1 receptor leads to the formation of a hydrogen-bond network with its catechol group and helices 3, 5, and 6, including water molecules. The para hydroxyl group of dopamine binds directly to S5.42 and N6.55, the latter also interacting with S5.43. Unexpectedly, S5.46 does not interact directly with the catechol; instead, it interacts through a water molecule with S5.42 and directly with T3.37. The formation of this hydrogen-bond network, part of which was previously observed in docking studies with dopamine agonists, triggers the opening of the E6.30-R3.60 ionic lock associated with the activation of GPCRs. These changes do not occur in the unbonded (apo) receptor or when it is in a complex with the antagonist 3-methoxy-5,6,7,8,9,14-hexahydrodibenz[d,g]azecine. Our results provide valuable insight into the T3.37-S5.46-water-S5.43-ligand interaction, which may be crucial to the activation of the D1 dopamine receptor and should be considered during the design of novel agonists. Graphical Abstract General representation of the relationship between the formation of the HBN and the opening of the R3.50-E6.30 ionic lock.

Evaluación de la Permeabilidad en Andamios Macroporosos de Bioglass 45S5 para Ingeniería de Tejidos / Permeability Evaluation of 45S5 Bioglass Macroporous Scaffolds for Bone Tissue Engenering

RESUMEN: Andamios macroporos de biovidro 45S5 han sido desarrollados como una alternativa para sustituir injertos de hueso tradicionales. Un factor crucial en el diseño de estos andamios es la permeabilidad ya que de esto dependerá su capacidad para remover desechos y suministrar nutrientes y oxígeno a las células. En este trabajo se llevó acabo la evaluación de la permeabilidad basados en la ley de Darcy de andamios macroporos de biovidrio 45S5 con porosidades en el rango de 69-74%. Los valores de permeabilidad obtenidos fueron de 4.19 × 10-10, 3.75 × 10-10 y 3.48 × 10-10 m 2 que estuvieron en el rango de los valores de permeabilidad del hueso trabecular.

ABSTRACT: Bioactive glass 45S5 foams were produced as an alternative to be used to fill and restore bone defects. A crucial design factor of foams is permeability, since it is related to their capability for waste removal and nutrients/oxygen supply to cells. In the present work a study was carried out to analyze the bioactive glass 45S5 foams permeability by Darcy's law. In the present work a study was carried out to analyze the bioactive glass 45S5 foams permeability by Darcy's law. The measure average permeability value on foams of 69-74 % porosity was 4.19 × 10-10, 3.75 × 10-10 y 3.48 × 10-10 m 2 , which are in the range of permeability values for trabecular bone.

Side chain flexibility and coupling between the S4-S5 linker and the TRP domain in thermo-sensitive TRP channels: Insights from protein modeling.

The transient receptor potential (TRP) superfamily is subdivided into several subfamilies on the basis of sequence similarity, which is highly heterogeneous but shows a molecular architecture that resembles the one present in members of the Kv channel superfamily. Because of this diversity, they produce a large variety of channels with different gating and permeability properties. Elucidation of these particular features necessarily requires comparative studies based on structural and functional data. The present study aims to compilate, analyze, and determine, in a coherent way, the relationship between intrinsic side-chain flexibility and the allosteric coupling in members of the TRPV, TRPM, and TRPC families. Based on the recently determined structures of TRPV1 and TRPV2, we have generated protein models for single subunits of TRPV5, TRPM8, and TRPC5 channels. With these models, we focused our attention on the apparently crucial role of the GP dipeptide at the center of the S4-S5 linker and discussed its role in the interaction with the TRP domain, specifically with the highly-conserved Trp during this coupling. Our analysis suggests an important role of the S4-S5L flexibility in the thermosensitivity, where heat-activated channels possess rigid S4-S5 linkers, whereas cold-activated channels have flexible ones. Finally, we also present evidence of the key interaction between the conserved Trp residue of the TRP box and of several residues in the S4-S5L, importantly the central Pro. Proteins 2017; 85:630-646. © 2016 Wiley Periodicals, Inc.

Ions Release and pH of Calcium Hydroxide-, Chlorhexidine- and Bioactive Glass-Based Endodontic Medicaments

Abstract This study evaluated pH and release of calcium, sodium and phosphate ions from different medications in human dentin. Fifty premolars were prepared and randomly divided into groups: (CHX) - 2% chlorhexidine gel; (CHX + CH) - CHX + calcium hydroxide PA; (CH) - CH + propylene glycol 600; (NPBG) - experimental niobium phosphate bioactive glass + distilled water; (BG) - bioactive glass (Bio-Gran) + distilled water. The specimens were immersed in deionized water and the pH variations were measured. The quantification of ions in the solutions was made by inductively coupled plasma - atomic emission spectroscopy (ICP/AES) at 10 min, 24 h, 7, 14, 21 and 30 days. The results were analyzed by ANOVA and Tukey`s test, with a significance level of 5%. CH had the highest level of calcium ions release at 30 days, while CHX and BG released more sodium ions. BG, NPBG and CHX released a higher amount of phosphate ions. The pH of CH was significantly higher compared with the other groups. CH favored the greatest increase of pH and calcium ions release. The bioactive glasses released more sodium and phosphate ions and presented an alkaline pH immediately and after 30 days.

Resumo Este estudo avaliou o pH e a liberação de íons cálcio, sódio e fosfato de diferentes medicamentos em dentina humana. Cinquenta pré-molares foram preparados e divididos aleatoriamente em grupos: (CHX) - clorexidina gel 2%; (CHX + CH) - CHX + hidróxido de cálcio PA; (CH) - CH + propilenoglicol 600; (NPBG) - vidro experimental nióbio fosfato bioativo + água destilada; (BG) - vidro bioativo (Bio-Gran) + água destilada. Os espécimes foram submersos em água deionizada e as variações de pH foram mensuradas. A quantificação dos íons nas soluções foi feita por espectrometria de emissão atômica com plasma indutivamente acoplado (ICP - AES) nos tempos de 10 min, 24 h, 7, 14, 21 e 30 dias. Os resultados foram analisados por ANOVA e teste Tukey, com um nível de significância de 5%. Verificou-se que CH a teve a maior liberação íons de cálcio ao final de 30 dias, enquanto CHX e BG liberaram mais íons de sódio. BG, NPBG e CHX apresentaram a maior liberação de íons fosfato. O pH de CH foi significativamente maior em comparação com os outros grupos testados. O grupo CH aumentou o pH e a liberação de íons cálcio. Os vidros bioativos obtiveram uma maior liberação de íons sódio e fosfato e apresentaram pH alcalino imediato e ao final de 30 dias.

Bioactive glass and connective tissue graft used to treat intrabony periodontal defects.

Different techniques and materials can be used to treat intrabony periodontal defects caused by periodontal diseases. This case report presents an intrabony periodontal defect with bioactive glass and connective tissue graft used as a barrier. Probing depth and clinical attachment gain were reduced at 6 and 12 months post-treatment.