Effect of adding fluoride to camellia sinensis against dentin erosion generated by non-bacterial acids / Efecto de la adición de flúor a la camellia sinensis frente a la erosión de dentina generada por ácidos no bacterianos

Introduction: Natural products are an option to be used in different conditions in the oral cavity, such as Camellia sinensis, which due to its different properties would be beneficial in the erosion of the dental surface. Objetive: Determinar el efecto del extracto de Camellia sinensis (C. sinensis) adicionado con flúor frente a la acción erosiva de ácidos no bacterianos en la superficie de la dentina humana. Materials and Methods: Quasi-experimental, prospective, longitudinal, and in vitro study, consisting of 50 samples of human dentin, which were classified into 5 study groups: distilled water, hydrochloric acid, 2% C. sinensis extract, sodium fluoride. 2% and 2% C. sinensis extract added with 2% sodium fluoride. The surface roughness of each sample was evaluated with the SRT6200 digital roughness meter, obtaining a total average roughness and the measurements were carried out in two moments. Results: It was observed that the 2% C. sinensis extract, the 2% sodium fluoride, and the C. sinensis extract added with 2% sodium fluoride, showed a variation in surface roughness between before and after, which was not significant (p<0.05) in all cases. It should be noted that the C. sinensis plus sodium fluoride group is the one that obtained the best variation in the mean surface roughness than the other groups studied. Conclusions: The 2% C. sinensis extract, 2% sodium fluoride, and the combination of both compounds demonstrated an inhibitory effect against the erosive action of hydrochloric acid (0.01 M) on the dentin surface, not presenting a statistically significant difference in the results.

Introducción: Los productos naturales son una opción para ser usados en diferentes afecciones en la cavidad bucal, como lo podría ser la Camellia sinensis, que por sus diferentes propiedades sería de beneficio en la erosión de la superficie dental. Objetivo: Determinar el efecto del extracto de Camellia sinensis (C. sinensis) adicionado con flúor frente a la acción erosiva de ácidos no bacterianos en la superficie de la dentina humana. Materiales y Métodos: Estudio cuasi experimental, prospectivo, longitudinal ein vitro, constituido por 50 muestras de dentina de dientes permanentes, que se clasificaron en 5 grupos de estudio: Agua destilada, ácido clorhídrico, extracto de C. sinensis a 2%, fluoruro de sodio al 2% y extracto de C. sinensisa 2% adicionado con fluoruro de sodio al 2%. Se evaluó la rugosidad superficial de cada muestra con el rugosímetro digital SRT6200, obteniéndose una rugosidad media total y se realizaron las mediciones en dos momentos. Resultado: Se observó que el extracto de C. sinensisal 2%, el fluoruro de sodio al 2% y el extracto de C. sinensis adicionado con fluoruro de sodio al 2%, presentaron una variación de la rugosidad superficial entre el antes y el después, no siendo esta significativa (p<0.05) en todos los casos. Cabe resaltar que el grupo C. sinensis más fluoruro de sodio, es el que obtuvo una mejor variación de la media de rugosidad superficial, que los otros grupos estudiados. Conclusión: El extracto de C. sinensisal 2%, el fluoruro de sodio al 2% y la combinación de ambos compuestos demostraron un efecto inhibitorio frente a la acción erosiva del ácido clorhídrico (0,01 M) en la superficie de dentina, no presentando una diferencia estadísticamente significativa en los resultados.

New Benzodihydrofuran Derivatives Alter the Amyloid ß Peptide Aggregation: Strategies To Develop New Anti-Alzheimer Drugs.

Alzheimer's disease is a neurodegenerative disorder that is the leading cause of dementia in elderly patients. Amyloid-ß peptide (1-42 oligomers) has been identified as a neurotoxic factor, triggering many neuropathologic events. In this study, 15 chalcones were synthesized employing the Claisen-Schmidt condensation reaction, starting from a compound derived from fomannoxine, a natural benzodihydrofuran whose neuroprotective activity has been proven and reported, and methyl aromatic ketones with diverse patterns of halogenated substitution. As a result, chalcones were obtained, with good to excellent reaction yields from 50 to 98%. Cytotoxicity of the compounds was assessed, and their cytoprotective effect against the toxicity associated with Aß was evaluated on PC-12 cells. Out of the 15 chalcones obtained, only the 4-bromo substituted was cytotoxic at most tested concentrations. Three synthesized chalcones showed a cytoprotective effect against Aß toxicity (over 37%). The 2,4,5-trifluoro substituted chalcone was the most promising series since it showed a cytoprotective impact with more than 60 ± 5% of recovery of cellular viability; however, 3-fluoro substituted compound also exhibited important values of recovery (50 ± 6%). The fluorine substitution pattern was shown to be more effective for cytoprotective activity. Specifically, substitution with fluorine in the 3,5-positions turned out to be particularly effective for cytoprotection. Furthermore, fluorinated compounds inhibited the aggregation rate of Aß, suggesting a dual effect that can be the starting point of new molecules with therapeutic potential.

Design, synthesis and biological evaluation of fluorinated selective estrogen receptor degraders (FSERDs) --- A promising strategy for advanced ER positive breast cancer.

Although endocrine therapies involving pharmaceuticals, such as tamoxifen and aromatase inhibitors, had initially demonstrated good responses in patients with estrogen receptor-positive (ER+) breast cancer, they often led to drug resistance. ER plays a vital role in the progression of metastatic diseases. Fulvestrant, a first generation selective estrogen receptor degrader (SERD), can effectively downregulate the ER protein and inhibit its downstream signaling pathways. However, as the drug needs to be intramuscularly injected, its widespread use is limited owing to poor patient compliance. Herein, we described a novel class of orally bioavailable fluorine-substituted SERDs that exhibit improved pharmacokinetic profiles. We substituted the hydroxyl group of clinical SERD candidate 6 with a fluorine atom to diminish phase II metabolism. The subsequent structure-activity relationship (SAR) investigation identified 22h and 27b, which can effectively degrade ER in a dose-dependent manner and exhibit considerable antiproliferative potency and efficacy in vitro and in vivo. The excellent pharmacokinetic profiles of 27b render it promising candidate of clinically useful oral SERD.

Evaluation of three different remineralizing agents on artificially demineralized enamel lesions: Using scanning electron microscopy-energy dispersive X-ray and magic-angle spinning nuclear magnetic resonance - An in vitro study.

Aim: Demineralization can be arrested or reversed when remineralization agents are applied to incipient carious or noncavitated carious lesions. A large number of therapeutic agents, including nonfluoridated products, have been developed to promote enamel remineralization. This study aims to evaluate the efficacy of different remineralizing agents on artificially demineralized enamel lesions. Materials and Methods: The present in vitro study was conducted on 75 sound premolars divided into three groups of normal, demineralized (n = 15 each), and remineralized teeth (n = 45). The remineralized teeth were further subdivided into three groups (n = 15) as remineralized with 2% sodium fluoride (NaF), 2% NaF, and Psoralea corylifolia (bakuchi) and white mineral trioxide aggregate. Specimens of each group were treated with the above-mentioned remineralizing agents and then subjected to Vickers hardness number (VHN), scanning electron microscopy-energy dispersive X-ray (SEM-EDX), and magic-angle spinning nuclear magnetic resonance (MAS-NMR) for further evaluation. Results: The test results showed significantly the highest VHN and the emission peak of elements under the EDX test, such as calcium, phosphorous, oxygen, and fluorine with remineralized with NaF + bakuchi. MAS-NMR spectra showed fluorine and phosphorous peak in a group with NaF + bakuchi indicative of the increase in remineralization. NaF + bakuchi showed effective results in VHN, SEM-EDX, and MAS-NMR with no antagonist interaction. Conclusion: Thus, P. Corylifolia presents an advantage in enhancing remineralization and inhibiting demineralization for early carious lesions and can be used as a herbal extract for effective reduction in pathogenic bacteria.

18F-FDG PET/CT for the Evaluation of Therapy Response in Hormone Receptor-Positive Bone-Dominant Metastatic Breast Cancer.

Fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT has shown promise for use in assessing treatment response in patients with bone-only or bone-dominant (BD) metastatic breast cancer (mBC). In this single-institution, prospective single-arm study of 23 women (median age, 59 years [range, 38-81 years]) with biopsy-proven estrogen receptor-positive bone-only or BD mBC about to begin new endocrine therapy between October 3, 2013, and August 3, 2018, the value of early 4-week 18F-FDG PET/CT in predicting progression-free survival (PFS) was evaluated. 18F-FDG PET/CT was performed at baseline, 4 weeks, and 12 weeks. Maximum standardized uptake value (SUVmax) and peak SUV (SUVpeak) were measured for up to five index lesions. The primary end point was PFS. Secondary end points were overall survival (OS) and time to skeletal-related events (tSREs). All end points were compared between responders (reduction of 30% or more in the sum of SUVmax for target lesions) and nonresponders at 4 weeks and 12 weeks. Percentage change from baseline in SUVmax at 4- and 12-week 18F-FDG PET/CT were highly correlated (r = 0.81). At the 4-week time point PET responders had numerically longer PFS (14.2 months vs 6.3 months; P = .53), OS (44.0 months vs 29.7 months; P = .47), and tSRE (27.4 months vs 25.2 months; P = .66) compared with nonresponders, suggesting the clinical utility of 4-week 18F-FDG PET/CT as an early predictor of treatment failure. Keywords: Breast Cancer, Metastatic Breast Cancer, Bone-Dominant Metastatic Breast Cancer, FDG PET/CT, Estrogen-Receptor Positive Metastatic Breast Cancer Supplemental material is available for this article. Clinical trial registration no. NCT04316117 © RSNA, 2022.

The current state of amyloidosis therapeutics and the potential role of fluorine in their treatment.

Amyloidosis, commonly known as amyloid-associated diseases, is characterized by improperly folded proteins accumulating in tissues and eventually causing organ damage, which is linked to several disorders ranging from neurodegenerative to peripheral diseases. It has an enormous societal and financial impact on the global health sector. Due to the complexity of protein misfolding and intertwined aggregation, there are no effective disease-modifying medications at present, and the condition is likely mis/non-diagnosed half of the time. Nonetheless, over the last two decades, substantial research into aggregation processes has revealed the possibilities of new intervention approaches. On the other hand, fluorine has been a rising star in therapeutic development for numerous neurodegenerative illnesses and other peripheral diseases. In this study, we revised and emphasized the possible significance of fluorine-modified therapeutic molecules and fluorine-modified nanoparticles (NPs) in the modulation of amyloidogenic proteins, including insulin, amyloid beta peptide (Aß), prion protein (PrP), transthyretin (TTR) and Huntingtin (htt).

Efficacy of Resin Infiltration and Fluoride Casein Phosphopeptide Amorphous Calcium Phosphate Varnish on Non-cavitated Active White Spot Lesions in Children: A Randomized Clinical Trial

Abstract Objective: To compare the efficacy of resin infiltration and fluoride casein phosphopeptide amorphous calcium phosphate varnish on non-cavitated active white spot lesions in 5-8 years old children. Material and Methods: 60 non-cavitated active white spot lesions in 60 patients with ICDAS II score 2 from both genders in the age range of 5 to 8 years were taken. Thirty lesions were treated by resin infiltration (Group 1) and 30 by Fluoride CPP-ACP varnish (Group 2). Resin infiltration was performed on the same day, while Fluoride CPP-ACP varnish was applied once a week for 4 weeks. The follow-up was done at 3, 6 months, and 12 months. Results: At 3, 6, and 12 months change in mean ICDAS II Score in group 1 was 1.5±0.5,1.13±0.73 and 0.9±0.88, respectively, while in group 2, it was observed to be 0.30±0.59, 0.4±0.89 and 0.06±0.82, respectively (p<0.001). Conclusion: Resin infiltration was more successful than Fluoride CCP-ACP varnish in active non-cavitated white spot lesions (AU).

Effect of Polishing Systems on Fluoride Release and Surface Roughness of Different Restorative Materials / El efecto de los sistemas de pulido en la liberación de flúor y rugosidad de diferentes materiales restauradores

ABSTRACT Secondary caries is an important factor in the replacement of the restorations, and it is thought that fluoride-releasing materials may prevent this problem. Furthermore, the fluoride release of the materials may be increased by polishing process. Available knowledge about the effect of polishing systems (PS) on the fluoride release of materials is limited. Therefore, this study was conducted to evaluate the effect of PS on the fluoride release of fluoride-containing materials. Restorative materials were divided into 6 groups: Fuji IX GP, Fuji II, Dyract XP, Beautifil II, Beautifil-Bulk, and Filtek Ultimate. Each group was also divided into four subgroups: Mylar strip, Sof-Lex Discs, Sof-Lex Diamond, and OneGloss. Fluoride release was determined using a fluoride ion-selective electrode. Surface roughness was evaluated with a profilometer. Two- way repeated measure and one-way ANOVA tests were used for statistical analysis. The initial rapid fluoride release was observed only in Fuji IX. The PS increased the fluoride release of Fuji IX and Fuji II and Dyract XP materials while reducing the fluoride release of resin-based materials. The highest surface roughness values were obtained with OneGloss. Further, a significant relationship between fluoride release and surface roughness was found. The polishing provides an increase in fluoride release, especially in glass-ionomer-based materials. This article revealed that there is a relationship between fluoride release and surface roughness. Proper PS must be chosen according to the material to provide the best clinical benefits in terms of fluoride release and surface roughness.

RESUMEN La caries secundaria es un factor importante para el reemplazo de restauraciones y se considera que los materiales que liberan flúor pueden prevenir este problema. Además, la liberación de fluoruro de estos materiales podría incrementarse mediante el proceso de pulido. El conocimiento disponible sobre el efecto de los sistemas de pulido (SP) en la liberación de fluoruro de los materiales es limitado. Por lo tanto, este estudio se realizó para evaluar el efecto de los SP sobre la liberación de fluoruro de materiales que contienen fluoruro. Los materiales de restauración se dividieron en 6 grupos: Fuji IX GP, Fuji II, Dyract XP, Beautifil II, Beautifil-Bulk y Filtek Ultimate. Cada grupo también se dividió en cuatro subgrupos: Banda Mylar, Discos Sof-Lex, Sof-Lex Diamond y OneGloss. La liberación de fluoruro se determinó usando un electrodo selectivo de iones fluoruro. La rugosidad de la superficie se evaluó con un perfilómetro. Se utilizaron medidas repetidas bidireccionales y pruebas ANOVA de una vía para el análisis estadístico. La liberación inicial rápida de fluoruro se observó solo en Fuji IX. El SP aumentó la liberación de fluoruro de los materiales Fuji IX y Fuji II y Dyract XP al tiempo que redujo la liberación de fluoruro de los materiales a base de resina. Los valores más altos de rugosidad de la superficie se obtuvieron con OneGloss. Además, se encontró una relación significativa entre la liberación de fluoruro y la rugosidad de la superficie. El pulido proporciona un aumento en la liberación de fluoruro, especialmente en materiales a base de ionómero de vidrio. Este artículo reveló que existe una relación entre la liberación de fluoruro y la rugosidad de la superficie. El SP adecuado debe elegirse de acuerdo con el material para proporcionar los mejores beneficios clínicos en términos de liberación de fluoruro y rugosidad de la superficie.

Estudo retrospectivo da efetividade de uma abordagem de tratamento não invasiva para inativação de lesões de cárie dentária não cavitadas em pacientes infantis / Effectiveness of a non-invasive treatment protocol for incipient enamel carious lesions in a child population: a retrospective study

Objetivo: Avaliar a efetividade de uma abordagem de tratamento não invasiva para a inativação de lesões não cavitadas de dentes decíduos e permanentes realizada na Clínica Infanto-Juvenil (CIJ) da Faculdade de Odontologia da Universidade Federal do Rio Grande do Sul (FO-UFRGS), identificando os fatores clínicos do paciente e associando-os ao sucesso clínico do tratamento. Métodos: Foram incluídos 55 prontuários de pacientes que receberam instruções de higiene bucal, controle de dieta e aplicações tópicas de flúor (ATF) na CIJ da FO-UFRGS entre 2016 e 2018. Foram coletados dados demográficos e clínicos referentes a avaliação da atividade de cárie dentária na consulta inicial e após o tratamento realizado: índice de placa visível (IPV), índice de sangramento gengival (ISG) e o número médio de dentes permanentes cariados, perdidos e restaurados (CPO-D) e/ou número médio de dentes decíduos cariados, extraídos ou com indicação de extração e restaurados (ceo-d). Na análise estatística foram utilizados os testes Qui-quadrado de Pearson, Exato de Fisher e Wilcoxon, nível de significância: p < 0,05. Resultados: Não houve diferença estatisticamente significativa quando se comparou as variáveis idade, sexo, IPV, ISG e ceo-d/CPO-D com o sucesso do tratamento. Houve diferença estatisticamente significativa comparando o IPV inicial com o final (p = 0,016) e número de lesões não cavitadas ativas inicial e final (p < 0,001), mas não houve diferença para o ISG inicial e final (p = 0,324). Conclusão: Baseado nos achados da redução do IPV e da redução no número de lesões não cavitadas ativas ao final do tratamento, sugere-se que a abordagem de tratamento não invasiva para inativação de lesões de cárie dentária não cavitadas aplicada na CIJ da FO-UFRGS é efetiva.

Aim: To evaluate the effectiveness of a non-invasive treatment on the arrest of non-cavitated caries lesions of primary and permanent teeth performed at the Pediatric Clinic (PC) at the Dental Teaching Hospital of the Federal University of Rio Grande do Sul (DT-UFRGS), identifying the patient's clinical factors and associating them with the clinical success of the treatment. Methods: This study included 55 patient's medical records who received oral hygiene instructions, diet control, and topical fluoride applications (TFA) at the PC of DT-UFRGS between 2016 and 2018. Demographic and clinical data regarding the evaluation of caries activity in the initial visit and after the performed treatment were collected: visible plaque index (VPI), gingival bleeding index (GBI), and DMF-T caries index (average number of decayed, missing, and restored permanent teeth), and/or dmf-t (average number of decayed, extracted or with recommendation for extraction, and restored deciduous teeth). Pearson's Chi-square, Fisher's Exact, and Wilcoxon tests were used for statistical analysis, significance level: p < 0.05. Results: No significant difference was observed when the variables of age, gender, VPI, CBI, DMF-T/dmf-t were compared with treatment success. A statistically significant difference was found when comparing the initial with the final VPI (p = 0.016), as well as the number of initial and final active non-cavitated carious lesions (p < 0.001), but no difference was identified for the initial and final GBI (p = 0.324). Conclusion: Based on the findings of VPI reduction and reduction in the number of active non-cavitated carious lesions upon completion of treatment, it is suggested that the non-invasive treatment for arrestment of non-cavitated carious lesions applied at the PC of DT-UFRGS is effective.

Estudo retrospectivo da efetividade de uma abordagem de tratamento não invasiva para inativação de lesões de cárie dentária não cavitadas em pacientes infantis / Effectiveness of a non-invasive treatment protocol for incipient enamel carious lesions in a child population: a retrospective study

Objetivo: Avaliar a efetividade de uma abordagem de tratamento não invasiva para a inativação de lesões não cavitadas de dentes decíduos e permanentes realizada na Clínica Infanto-Juvenil (CIJ) da Faculdade de Odontologia da Universidade Federal do Rio Grande do Sul (FO-UFRGS), identificando os fatores clínicos do paciente e associando-os ao sucesso clínico do tratamento. Métodos: Foram incluídos 55 prontuários de pacientes que receberam instruções de higiene bucal, controle de dieta e aplicações tópicas de flúor (ATF) na CIJ da FO-UFRGS entre 2016 e 2018. Foram coletados dados demográficos e clínicos referentes a avaliação da atividade de cárie dentária na consulta inicial e após o tratamento realizado: índice de placa visível (IPV), índice de sangramento gengival (ISG) e o número médio de dentes permanentes cariados, perdidos e restaurados (CPO-D) e/ou número médio de dentes decíduos cariados, extraídos ou com indicação de extração e restaurados (ceo-d). Na análise estatística foram utilizados os testes Qui-quadrado de Pearson, Exato de Fisher e Wilcoxon, nível de significância: p < 0,05. Resultados: Não houve diferença estatisticamente significativa quando se comparou as variáveis idade, sexo, IPV, ISG e ceo-d/CPO-D com o sucesso do tratamento. Houve diferença estatisticamente significativa comparando o IPV inicial com o final (p = 0,016) e número de lesões não cavitadas ativas inicial e final (p < 0,001), mas não houve diferença para o ISG inicial e final (p = 0,324). Conclusão:Baseado nos achados da redução do IPV e da redução no número de lesões não cavitadas ativas ao final do tratamento, sugere-se que a abordagem de tratamento não invasiva para inativação de lesões de cárie dentária não cavitadas aplicada na CIJ da FO-UFRGS é efetiva.

Aim: To evaluate the effectiveness of a non-invasive treatment on the arrest of non-cavitated caries lesions of primary and permanent teeth performed at the Pediatric Clinic (PC) at the Dental Teaching Hospital of the Federal University of Rio Grande do Sul (DT-UFRGS), identifying the patient's clinical factors and associating them with the clinical success of the treatment. Methods: This study included 55 patient's medical records who received oral hygiene instructions, diet control, and topical fluoride applications (TFA) at the PC of DT-UFRGS between 2016 and 2018. Demographic and clinical data regarding the evaluation of caries activity in the initial visit and after the performed treatment were collected: visible plaque index (VPI), gingival bleeding index (GBI), and DMF-T caries index (average number of decayed, missing, and restored permanent teeth), and/or dmf-t (average number of decayed, extracted or with recommendation for extraction, and restored deciduous teeth). Pearson's Chi-square, Fisher's Exact, and Wilcoxon tests were used for statistical analysis, significance level: p < 0.05. Results: No significant difference was observed when the variables of age, gender, VPI, CBI, DMF-T/dmf-t were compared with treatment success. A statistically significant difference was found when comparing the initial with the final VPI (p = 0.016), as well as the number of initial and final active non-cavitated carious lesions (p < 0.001), but no difference was identified for the initial and final GBI (p = 0.324). Conclusion: Based on the findings of VPI reduction and reduction in the number of active non-cavitated carious lesions upon completion of treatment, it is suggested that the non-invasive treatment for arrestment of non-cavitated carious lesions applied at the PC of DT-UFRGS is effective.

Targeted, Stimuli-Responsive, and Theranostic 19F Magnetic Resonance Imaging Probes.

Unlike conventional 1H magnetic resonance imaging (MRI), 19F MRI features unambiguous detection of fluorine spins due to negligible background signals. Therefore, it is considered a promising noninvasive and selective imaging method for the diagnosis of cancers and other diseases. For 19F MRI, fluorine-rich molecules such as perfluorocarbons (PFC) have been formulated into nanoemulsions and used as its tracer agent. Along with advancements in other types of nanoparticles as targeted theranostics and stimuli-triggered probes and combined with the advantages of 19F MRI, PFC nanoemulsions are being empowered with these additional functionalities and becoming a promising theranostic platform. In this Review, we provide an overview of fluorine-based materials for sensitive 19F MRI of biological and pathological conditions. In particular, we describe designs and applications of recently reported stimuli-responsive and theranostic 19F MRI probes. Finally, challenges and future perspectives regarding the further development of 19F MRI probes for their clinical applications are described.

Fluoride Release of Giomer and Resin Based Fissure Sealants / Liberación de flúor de sellantes de fosas y fisuras a base de resina y/o ionómero

ABSTRACT Fissure sealants are applied to teeth to prevent caries development. The presence of the fissure sealant creates a protective barrier, which prevents plaque accumulation to the pits and fissure. They have a significant role in preventing pit and fissure caries. The aim of this study was to evaluate the time-dependent fluoride ion release of giomer- and resin-based fissure sealants. Fissure sealants were divided into 4 groups: BeautiSealant (Shofu, Japan), Clinpro Sealant (3M ESPE, USA), Helioseal F (Ivoclar Vivadent, Liechtenstein), Fissurit F (Voco, Germany). Disk shaped samples were prepared for each sealant material tested, and they were transferred into polyethylene vials containing 5 ml of deionized water. Fluoride ion diffusion was determined on days 1,2,3,7,14,21, and 28 (n=7). The fluoride concentration in these samples was analyzed using a pre-calibrated spectrophotometer in parts per million (ppm). These experiments were performed in triplicates at room temperature. ANOVA and Tukey's HSD test were used for statistical analysis. BeautiSealant was released the highest amount of fluoride on day 1 (5.33 ppm), followed by a sudden decrease on the day 2 (2.17ppm). The burst effect was observed only in this group. Clinpro Sealant, Fissurit F and HelioSeal F groups presented fluoride release of 2.69, 2.94 and 2.91 ppm on the first day, respectively, without a significant difference (p>0.05). After the first week, a constant fluoride release level has been reached. The fluoride release for the three resin-based fissure sealants was slightly lower than that for the giomer-based. After the first week, materials exhibited no significant difference and reached a plateau. The usage of a high and prolonged fluoride-releasing fissure sealant material should be considered by clinicians, particularly in patients with caries risk.

RESUMEN Los sellantes de fosas y fisuras se utilizan con el objetivo de prevenir el desarrollo de caries. La presencia del sellante crea una barrera protectora, que evita la acumulación de placa en las fosas y fisuras. Tienen un papel importante en la prevención de la caries. El objetivo de este estudio fue evaluar la liberación de iones fluoruro de los sellantes de fosas y fisuras a base de Ionómeros y resinas. Los sellantes de fosas y fisuras se dividieron en 4 grupos: BeautiSealant (Shofu, Japón), Clinpro Sealant (3M ESPE, EE. UU.), Helioseal F (Ivoclar Vivadent, Liechtenstein), Fissurit F (Voco, Alemania). Se prepararon muestras en forma de disco para cada material, y se transfirieron a viales de polietileno que contenían 5 ml de agua desionizada. La difusión de iones fluoruro se determinó en los días 1,2,3,7,14,21 y 28 (n=7). La concentración de fluoruro en estas muestras se analizó utilizando un espectrofotómetro precalibrado en partes por millón (ppm). Estos experimentos se realizaron por triplicado a temperatura ambiente. ANOVA y la prueba de HSD de Tukey se utilizaron para el análisis estadístico. BeautiSealant liberó la mayor cantidad de fluoruro en el día 1 (5.33 ppm), seguido por una disminución repentina en el día 2 (2.17ppm). Los grupos Clinpro Sealant, Fissurit F y HelioSeal F presentaron una liberación de fluoruro de 2.69, 2.94 y 2.91 ppm el primer día, respectivamente, sin una diferencia significativa (p> 0.05). Posterior a la primera semana, fue alcanzado un nivel constante de liberación de fluoruro. La liberación de flúor para los tres sellantes de fosas y fisuras a base de resina fue ligeramente inferior a la de los Ionómeros. Después de la primera semana, los materiales no mostraron diferencias significativas. Los odontólogos deben considerar el uso de un material sellante de fosas y fisuras que promueva la liberación de flúor a lo largo del tiempo, especialmente en pacientes con riesgo de caries.

Identification and Analysis of the Fluoride Concentration in Toothpastes Intended for Children

Objective: To identify the commercially available toothpastes intended for children and their total soluble fluoride concentrations (TSF). Material and Methods: Twelve brands of toothpastes intended for children marketed in supermarkets and pharmacies were found and analyzed: Bitufo®; Colgate Smile®; Lilica Ripilica®; Even Baby®; Turma da Mônica Baby®; Loney Tunes®; Loney Tunes Baby®; Malvatrikds Baby®; Oral B Stages®; Sanifil Kids®; Tandy®; Tra-lálá Baby®. Duplicate samples of each toothpaste were weighed (+/- 90 to 110 mg) and diluted in 10 mL of distilled water under stirring. To evaluate soluble fluoride, duplicate aliquots of supernatant suspensions were evaluated on specific ion fluoride electrode calibrated with fluoride standard solutions and results expressed in ppm F according to established protocol. Results: According to information provided by manufacturers, 5 non-fluoridated toothpastes, 3 toothpastes with less than 1000 ppm F and 4 toothpastes with conventional fluoride concentration (1100 ppm F) were identified. After analysis of soluble fluoride of fluoridated toothpastes, only 02 presented TSF concentration equal to or greater than 1000 ppm F. The TSF concentration (mean ± SD) for all samples ranged from 8.2 ± 0.1 to 1065.9 ± 24.7 ppm F. Conclusion: Few toothpastes intended for children presented soluble fluoride concentrations capable of preventing dental caries. Additionally, regulatory measures need to be implemented for the marketing of toothpastes intended for children with at least 1000 ppm of soluble fluoride, especially in locations without other sources of fluoride (fluoridated water) for the population.

Design, synthesis, and evaluation of fluorine and Naphthyridine-Based half-sandwich organoiridium/ruthenium complexes with bioimaging and anticancer activity.

A range of fluorine and naphthyridine-based half-sandwich iridium (III) and ruthenium (II) complexes were synthesized. The iridium complexes possessed excellent antiproliferative properties, a substantial improvement over cisplatin, especially the best 1C containing the fluorine atom and 2C containing the naphthyridine. On the contrary, the ruthenium complexes displayed much less antiproliferative activity. Two X-ray crystal structures were determined. The cytotoxicity of the complexes can be changed flexible by regulating the metal center and the ancillary ligands. The best complex 1C was chose to study further on the mechanism of action. The chemical reactivity such as hydrolysis, reaction with nucleobases, glutathione and catalytic conversion of NADH to NAD+, were investigated. Complex 1C can react with 9-ethylguanine (9-EtG) and catalyze oxidation of NADH. In addition, the self-luminescence of the complex 1C was also successfully used in confocal microscopy images for elucidating the subcellular localization. Complex 1C specifically targeted to lysosomes in A549 cancer cells and caused lysosomal damages and promote cathepsin B released. Flow cytometry studies confirmed that the biological effects of this type of complexes induced apoptosis, especially late apoptosis. Our results suggested that changes in the mitochondria membrane potential were responsible for apoptosis. The chemistry and biological studies has showed that this class of metal complexes are worthy of further exploration for the design of novel anticancer drugs.

5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as a third-line chemotherapy treatment in metastatic gastric cancer, after failure of fluoropyrimidine, platinum, anthracycline, and taxane.

Studies on the effects of third-line chemotherapy (CT) in advanced gastric cancer (GC) patients are still scarce. The aim of this study was to evaluate the efficacy and safety of the modified 5-fluorouracil, leucovorin, and irinotecan (mFOLFIRI) regimen as a third-line CT in metastatic GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane. After failure of first- and second-line therapies, 42 patients received third-line FOLFIRI (180 mg/m² irinotecan and 400 mg/m² leucovorin administered concomitantly as a 90-minute intravenous (IV) infusion on day 1, followed by a 400 mg/m² 5-fluorouracil IV bolus then 2600 mg/m² continuous infusion over 46 hours), between January 2009 and December 2015. FOLFIRI was administered for a median of 6 cycles (range 4-12 cycles). Eight patients achieved partial response, while 13 patients showed stable disease, resulting in the overall response rate (ORR) of 19% and disease control rate (DCR) of 50%. The most frequent grade 3-4 hematological and non-hematological toxicities were neutropenia (14.2%) and diarrhea (7.1%). The median progression-free survival (PFS) and overall survival (OS) from the start of third-line CT were 3.8 months (95% confidence interval [CI], 3.0-4.5) and 6.8 months (95% CI, 5.6-7.9), respectively. According to the multivariate analysis, two factors were independently predictive of the poor OS: >2 regions of metastasis (relative risk [RR], 2.6; 95% CI, 1.3-5.4) and a high level of carcinoembryonic antigen [CEA] (RR, 3.4; 95% CI, 1.6-7.4). In conclusion, FOLFIRI was well tolerated as third-line CT and showed promising PFS and OS in advanced GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane.

The effects of fluorine substitution on the chemical properties and inhibitory capacity of Donepezil anti-Alzheimer drug; density functional theory and molecular docking calculations.

Drug fluorination has the potential to reproduce useful drugs with decreasing the side effect of them. Identifying the effect of this improvement on the chemical properties and biological interactions of drug symbolizes a meaningful progress in drug design. Here the fluorination of Donepezil as an anti-Alzheimer drug, including 7 fluorinated derivatives of it, was investigated computationally. In the first part of our calculations, the most important chemical properties of drug that affects the drug efficiency were investigated by applying the M06/6-31g (d, p) and M062X/6-31g (d, p) levels of theories. Findings showed that the fluorine substitution changed the drug stability as altered the solubility and molecular polarity. Furthermore, the intramolecular hydrogen bonding, charge distribution and electron delocalization of the drug were affected by this replacement. In the second section, the effect of fluorination on the drug⋯enzyme interactions was evaluated by using two effective methods Based on the molecular docking and density functional theory (DFT) calculations fluorine substitution influenced the Donepezil⋯Acetylcholinesterase interactions. Calculated binding energies by two computational methods displayed that the fluorine replacement changed the binding affinity of drug. Finally, the most significant non-bonded interactions between drugs and involved residues were investigated by bond length data analysis.

Impacto de um dentifrício contendo silicato de cálcio, fosfato e flúor no desgaste erosivo da dentina / Impact of a dentifrice containing calcium silicate, phosphate, and fluoride on erosive dentin wear

O presente estudo teve como objetivo avaliar in situ a eficácia da aplicação do dentifrício com adição de silicato de cálcio, fosfato e flúor na prevenção do desgaste erosivo, considerando os episódios de erosão e/ou abrasão da dentina. Utilizando um protocolo in situ, após a confecção dos blocos de dentina de dentes bovinos, foi realizada a dureza de superfície para seleção dos espécimes e a análise do perfil inicial. Por conseguinte, os espécimes foram distribuídos em dispositivos intrabucais utilizados pelos voluntários previamente selecionados, após o cálculo da amostra. Os grupos em estudo foram GI e GII aplicação de dentifrício com adição de silicato de cálcio, fosfato e flúor (REGENERATE Enamel Science), pH 9,60; controles positivos GIII e GIV - aplicação de dentifrício AmF-NaF-SnCl2 (Elmex® EROSION PROTECTION), pH 4,54; e controles negativos GV e GVI - aplicação de água; sendo que os grupos pares foram submetidos a erosão (ERO) e os ímpares a erosão mais abrasão (ERO+ABR). O estudo foi randomizado, cruzado e cego para o pesquisador, contendo três fases, de acordo com cada tratamento experimental, controle positivo e controle negativo. Em cada uma das fases in situ de cinco dias, 16 voluntários utilizaram dispositivos palatinos (quatro blocos: dois ERO e dois ERO+ABR), os quais 4x/dia eram imersos em ácido cítrico 0,5% por 2 minutos e 2x/dia o voluntário aplicava solução de dentifrício, concentração 1:3 (slurry) ou água, de acordo com cada tratamento, nos quatro espécimes após a primeira e terceira ciclagem. Em dois deles, a escovação era realizada com escova elétrica por 15 segundos por espécime, para simular episódios de abrasão, após a aplicação do slurry. A variável de resposta adotada foi a perfilometria. Os dados foram analisados por ANOVA a dois critérios e teste de Tukey (p<0,05). A perda de dentina foi semelhante para erosão e erosão associada à abrasão. O tratamento com dentifrício Elmex foi capaz de prevenir a perda em dentina de 23% para erosão e 26% para erosão associada à abrasão, sendo a perda de dentina estatisticamente menor, que o dentifrício Regenerate e o controle água, sendo que os dois últimos resultaram em desgaste estatisticamente semelhante. Conclui-se que o uso do dentifrício contendo silicato de cálcio, fosfato de sódio e flúor não foi capaz de diminuir a perda de dentina frente a desafios erosivos e abrasivos.(AU)

This study aimed to evaluate the effectiveness of in situ application of a dentifrice containing calcium silicate, phosphate, and fluoride on the prevention of erosive wear, considering the episodes of dentin erosion and/or abrasion. This was an in situ study. After the construction of the dentin blocks from bovine teeth, the surface hardness was performed to select the specimens followed by the initial profile analysis. Then, the specimens were placed in intraoral devices used by previously selected volunteers, after the sample size calculation. The study groups were: GI and GII application of dentifrice containing calcium silicate, phosphate, and fluoride (REGENERATE Enamel Science ) pH 9,60; positive controls GIII and GIV - application of AmF-NaF-SnCl2 dentifrice (Elmex® EROSION PROTECTION) pH 4,54; and negative controls GV and GVI - application of water. The even-numbered groups were subjected to erosion (ERO) and the odd-numbered groups to erosion and abrasion (ERO + ABR). This randomized, cross, and blinded study had three stages (one per type of treatment). In each of the 5-day in situ stages, 16 volunteers worn the palatal devices (4 blocks: 2 ERO and 2 ERO + APR), which were immersed into 0.5% citric acid, for 2 min, 4x/day. The volunteer applied either the dentifrice slurry (1:3 concentration) or water on the four specimens, 2x/day after the first and third cycling. On two specimens, toothbrushing was performed with electric toothbrush for 15 s per specimen, to simulate episodes of abrasion, after slurry application. The response variable adopted was the profilometry. Data were analyzed by two-way ANOVA and Tukey test (p<0.05). The dentin loss was similar both for erosion and erosion associated to abrasion. Treatment with Elmex dentifrice promoted a dentin loss of 23% for erosion and 26% for erosion associated with abrasion, with statistically smaller than that of the dentifrice Regenerate and the water control. The water control had a wear statistically similar to the dentifrice Regenerate. In conclusion, the use of a dentifrice containing calcium silicate, sodium phosphate, and fluoride was not able to decrease the dentin loss after erosive and abrasive challenges.(AU)

[Application study on regional infusion chemotherapy by celiac trunk during operation in advanced gastric cancer patients].

OBJECTIVE: To explore the feasibility, safety and efficacy of intraoperative regional infusion chemotherapy by celiac trunk in advanced gastric cancer patients. METHODS: One hundred and twenty-six patients with advanced gastric cancer(stageII(-III() were screened from database of Gastrointestinal Surgery Department of Taizhou People's Hospital between January 2008 and December 2010 who underwent R0 resection and D2 lymphadenectomy, received postoperative chemotherapy(XELOX or FOLFOX), and had complete follow-up data. They were divided into infusion chemotherapy group (65 cases) and control group (61 cases) according to regional infusion chemotherapy or not (fluorine 1 000 mg and cisplatin 60 mg). The side effects of chemotherapy, parameters related to the operation, long-term survival and relapse rate were compared between the two groups. RESULTS: The baseline data between the two groups were comparable(all P>0.05). Postoperative III( and IIII( adverse reaction of chemotherapy was not significantly different between the two groups (P>0.05). The time of postoperative intestinal function recovery [(67.9±14.8) hours vs. (68.9±15.0) hours, t=-0.380, P=0.705), volume of postoperative 1-week drainage [(66.1±17.1) ml vs.(61.9±18.2) ml, t=1.478, P=0.142], recent morbidity of complications[55.4%(36/65) vs. 49.2%(30/61), χ2=0.256, P=0.613], and the long-term morbidity of complications [16.9% (11/65) vs. 14.8% (9/61), χ2=0.111, P=0.739] were all not significantly different between the two groups. The 3-year survival rate and 3-year relapse-free survival rate in infusion chemotherapy group were significantly higher than those in control group(58.4% vs. 37.7%, χ2=5.382, P=0.020; 58.4% vs. 34.4%, χ2=6.636, P=0.010). CONCLUSION: Regional infusion chemotherapy by celiac trunk during operation for advanced gastric cancer patients is safe and feasible, and can reduce the risk of local recurrence and improve survival rate.

Tratamento de manchas brancas associadas ao tratamento ortodôntico / Treatment of white spots during orthodontic treatment

O aparecimento de mancha branca durante o tratamento ortodôntico é um problema clínico relevante. O objetivo deste trabalho foi destacar possíveis tratamentos da mancha branca durante e após o tratamento ortodôntico. Analisando a literatura encontrada tem-se que os principais tratamentos são: o controle do biofilme dental, microabrasão, aplicação de flúor (verniz, gel, dentifrício e enxaguatório), laser de argônio e fosfopeptídeo caseína-fosfato de cálcio amorfo (CPP-ACP). A condição dentária, principalmente o controle do biofilme dental, deve ser rigorosamente avaliada pelo ortodontista, para evitar o aparecimento das manchas brancas.

The white spot appearance during orthodontic treatment is an important clinical problem. The objective of this study was to highlight possible treatments of white spot during and after orthodontic treatment. The literature review has demonstrated that the main treatments are biofilm control, sandblasting fluoride application (varnish, gel, toothpaste and mouthwash), argon laser and amorphous calcium phosphate-casein phosphopeptide (CPP-ACP). The dental health, particularly the control of the biofi lm must be rigorously evaluated by the orthodontist to prevent the appearance of white spots.