Mechanisms of brain damage caused by inorganic fluoride using proteomics-based techniques / 环境与职业医学

Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L−1), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L−1), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg−1). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Effect of low concentration of sodium fluoride on osteogenic/odontogenic differentiation of human dental pulp cells / 口腔疾病防治

Objective@#To study the effect of low concentrations of sodium fluoride on the osteogenic/odontogenic differentiation of human dental pulp cells (hDPCs) in vitro.@*Methods@#This study was reviewed and approved by the Ethics Committee. hDPCs were cultured using a modified tissue explant technique in vitro. The effects of different concentrations of sodium fluoride on the proliferation of hDPCs were measured by methylthiazol tetrazolium (MTT) assay. Appropriate concentrations were added to the osteogenic/odontogenic differentiation induction medium, and the cells were induced in vitro. Alizarin red S staining was used to detect the osteoblastic/odontogenic differentiation ability of the cells, and the mRNA expression of the key differentiation factors was detected by RT-qPCR. Moreover, the expression of key molecules of endoplasmic reticulum stress (ERS) was detected by RT-qPCR and Western blot. The data were analyzed with the SPSS 18.0 software package.@*Results@#Low concentration of NaF (0.1 mmol/L) could stimulate cell proliferation in vitro, while a high concentration (5-10 mmol/L) could inhibit cell proliferation (P<0.05). According to the literature and the experimental data, 0.1 mmol/L NaF was selected as the following experimental concentration. The levels of alizarin red S staining were increased after NaF induction of mixed osteogenic/odontogenic differentiation in vitro. The mRNA expression levels of key molecules for osteogenic/odontogenic differentiation, dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP) and osteocalcin (OCN), were increased (P<0.05). The mRNA levels of ERS markers (splicing x-box binding protein-1 (sXBP1), glucose-regulated protein 78 (GRP78) and activating transcription Factor 4 (ATF4) were increased in NaF-treated cells. The protein expression levels of key ER stress molecules (phosphorylated RNA-activated protein kinase-like ER-resident kinase (p-PERK), phosphorylated eukaryotic initiation factor-2α (p-eIF2α) and ATF4) were higher in NaF-treated cells.@*Conclusion@#A low concentration of NaF promotes the osteogenic/odontogenic differentiation of hDPCs and increases the level of ER stress.

Fluoride in drinking groundwater and prevalence of fluorosis in children and adolescents: A systematic review / Fluoruro en el agua subterránea potable y prevalencia de fluorosis en niños y adolescentes: Una revisión sistemática

ABSTRACT Fluorosis is a worldwide public health problem. One of the factors related to it is the type of water consumed, such as groundwater. High fluoride concentration in groundwater may be explained by contamination from local industries. Since fluoride and arsenic are the main pollutants of groundwater, some studies correlate groundwater consumption with high prevalence of fluorosis Aim The aim of this study was to conduct a systematic review to determine whether children's risk of fluorosis is related to drinking groundwater Materials and Method The protocol for this systematic review was registered at the National Institute of Health Research Database (CRD42021227298). A comprehensive search was conducted to identify potentially relevant studies by exploring a range of electronic databases (Medline via PubMed, Scopus, Cochrane Library, Science Direct, Web of Science Core Collection, Medline via Ovid, Lilacs, Embase, and grey literature) Results A total 2189 articles were found. After reading titles and abstracts, 63 were selected for screening, and the final data was extracted from 15 articles Conclusion A relationship was identified between drinking fluoridated water from wells and the prevalence of fluorosis in individuals up to 18 years old. This is the first study to assess the issue systematically worldwide.

RESUMEN La fluorosis es un problema de salud pública a nivel mundial y el tipo de agua consumida es uno de los factores relacionados con ella, como el consumo de aguas subterráneas. La alta concentración de fluoruro en estas aguas puede justificarse por la contaminación por industrias locales y las características del suelo, donde algunos estudios correlacionan el consumo de aguas subterráneas con una alta prevalencia de fluorosis, ya que el fluoruro, junto con el arsénico, se consideran los principales contaminantes de estas aguas Objetivo El objetivo es realizar una revisión sistemática que relacione el riesgo de fluorosis en niños expuestos al consumo de agua procedente de pozos Materiales y Método El protocolo de esta revisión sistemática fue registrado en el National Institute of Health Research Database (CRD42021227298). Se realizó una búsqueda bibliográfica de estudios primarios explorando diversas bases de datos electrónicas (Medline vía PubMed, Scopus, Cochrane Library, Science Direct, Web of Science Core Collection, Medline vía Ovid, Lilacs, Embase y literatura gris) Resultados Se encontraron 2189 artículos, tras la lectura de títulos y resúmenes se seleccionaron 63 referencias para examinar y, finalmente, se extrajeron los datos de 15 artículos Conclusiones Se identificó una relación entre el consumo de agua fluorada de pozo y la prevalencia de fluorosis en individuos de hasta 18 años, siendo este estudio el primero en evaluarlo sistemáticamente a nivel mundial.

Determination of bioavailable fluoride in toothpastes marketed in Medellín, Colombia, through capillary electrophoresis / Fluoruro biodisponible en cremas dentales comercializadas en Medellín ­ Colombia mediante electroforesis capilar

Currently, the FDI recommendation (World Dental Federation) for fluoride concen­tration in toothpastes is that the total fluoride content declared by manufacturers be between 1,000 and 1,500 ppm, and of this amount, at least 800 ppm should be bioavai­lable fluoride. The aim of this study was to describe the market of toothpastes marketed in Medellín and to measure the concentration of bioavailable fluoride by capillary elec­trophoresis to verify their compliance with the FDI recommendation for the prevention of dental caries. After sampling the toothpastes available for sale in the 16 communes of the city of Medellin, a single operator measured in triplicate the concentration of bioavailable fluoride in 36 samples of previously blinded toothpastes using the capi­llary electrophoresis (EC) technique. Most of the evaluated toothpastes that declared a content of 1,000­1,500 ppm fluoride met the recommendation of presenting at least 800 ppm bioavailable fluoride. Measurement of bioavailable fluoride in toothpastes with MFP (sodium monofluorophosphate) is recommended, as it is known that binding to the abrasive can decrease its concentration over time.

Actualmente la recomendación de la FDI (Federación Dental Internacional) sobre la concentración de fluoruro en cremas dentales es que el contenido de fluoruro total de­clarado por los fabricantes sea entre 1.000 y 1.500 ppm, y que de esta cantidad al menos 800 ppm sea fluoruro biodisponible. El objetivo de este estudio fue describir el mercado de las cremas dentales comercializadas en Medellín y medir en estas la concentración de fluoruro biodisponible por electroforesis capilar para verificar su cumplimiento de la recomendación de la FDI para la prevención de la caries dental. Luego de realizar un mues­treo en las 16 comunas de la ciudad de Medellín sobre las cremas dentales disponibles a la venta, un solo operador midió por triplicado la concentración de fluoruro biodisponible en 36 muestras de cremas dentales previamente cegadas, mediante la técnica de electroforesis capilar (EC). La mayoría de las cremas dentales evaluadas que declaraban contenido de 1.000 a 1.500 ppm de fluoruro, cumplieron la recomendación de presentar al menos 800 ppm de fluoruro biodisponible. Se recomienda realizar la medición del fluoruro biodisponible en las cremas con MFP, ya que se conoce que la unión al abrasivo puede disminuir su concentración en el tiempo.

¿Cómo Intervenir el Proceso de Caries en Personas Mayores? Adaptación del Consenso de ORCA/EFCD/DGZ

Los cambios demográficos y epidemiológicos actuales determinarán un aumento en la prevalencia e incidencia de caries, específicamente lesiones de caries radicular (RCLs, por sus siglas en inglés) en personas mayores, por lo que la necesidad de tratamiento de mayor cobertura y efectividad será también cada vez mayor. Este artículo resume en español la evidencia actual disponible acerca de las recomendaciones clínicas para las intervenciones preventivas, no invasivas, micro o mínimamente invasivas e invasivas para el manejo de la caries dental en personas mayores, con especial énfasis en RCLs. La presente publicación se basa en un taller de consenso, seguido de un proceso de consenso e-Delphi, realizado por un panel de expertos nominados por la Organización Europea para la Investigación en Caries (ORCA), la Federación Europea de Odontología Conservadora (EFCD) y la Federación Alemana de Odontología Conservadora (DGZ). El propósito de este artículo es presentar las principales conclusiones alcanzadas en el consenso de ORCA/EFCD/DGZ para permitir una mejor difusión del conocimiento y la aplicación de estos conceptos en la práctica clínica, orientando la correcta toma de decisiones en el manejo de la enfermedad y RCLs en las personas mayores.

Current demographic and epidemiological changes will condition increased caries prevalence and incidence, specifically root caries lesions (RCLs) in the elderly. There will be a need, therefore, for therapeutic approaches with greater coverage and effectiveness. This article summarizes, in Spanish, the current available evidence leading to clinical recommendations for preventive, non-invasive, micro or minimally invasive and invasive interventions for the management of dental caries in older people, with special emphasis on RCLs. This publication is based on a consensus workshop, followed by an e-Delphi consensus process, conducted by a panel of experts nominated by the European Organization for Caries Research (ORCA), the European Federation of Conservative Dentistry (EFCD) and the German Federation of Conservative Dentistry (DGZ). The purpose of this article is to present the main conclusions reached in the ORCA/EFCD/DGZ consensus to allow a better dissemination of knowledge and the application of these concepts in clinical practice, guiding the correct decision-making for the disease management and the RCLs in the elderly.

Fluorosis dental en adolescentes de instituciones educativas de Lima, Perú / Dental fluorosis in adolescents from Educational Institutions in Lima, Peru

Introducción: La fluorosis dental es una patología endémica causada por la ingestión excesiva de fluoruros que pueden producir una alteración durante el desarrollo del esmalte, y es considerado un importante problema de salud pública porque afecta la salud bucal y sistémica de la población. Objetivo: Este estudio tuvo como idea principal determinar la frecuencia y los niveles de fluorosis dental en escolares de 12 a 15 años pertenecientes a dos instituciones educativas de Lima - Perú. Método: Se realizó un estudio descriptivo de tipo transversal, la muestra estuvo conformada por 252 estudiantes, entre 12 y 15 años de dos centros educativos de Lima. El muestreo fue por selección sistemática de elementos muestrales. La fluorosis dental se evalúo mediante el Índice de Dean. Para determinar la frecuencia y los niveles de fluorosis dental, se realizó un examen clínico bucal y se desarrolló un cuestionario validado previamente. Resultados: La frecuencia de fluorosis dental fue de 44,8% (n=113) afectando más a los varones en un 27,39% (n=69) y a los adolescentes de 13 años (15,1%). En relación con los niveles de fluorosis, predominó el tipo "muy leve" (34,9%). También se encontró una asociación entre la presencia y el nivel de fluorosis con el número de aplicaciones de flúor (p<0,05). Además, se dijo que el índice comunitario de fluorosis de Dean fue de 0,43. Conclusiones: En la población escolar evaluada, la frecuencia de fluorosis fue de 44,8% y el nivel predominante de fluorosis fue muy leve. Además, el índice comunitario fue de 0,43, el cual mostró un nivel límite de importancia para la salud pública. Por lo que se puede considerar que el número de aplicaciones tópicas de flúor recibido por la población sin una planificación adecuada se podría convertir en un factor de riesgo para causar fluorosis dental.

Introduction: Dental fluorosis is an endemic pathology caused by the excessive ingestion of fluorides that can produce an alteration during the development of the enamel and is considered an important public health problema because it affects the oral and systemic health of the population. Objective: The objective of this study was to determine the frequency and levels of dental fluorosis in school children between 12 and 15 years of age belonging to two educational institutions in Lima, Peru. Method: A descriptive cross-sectional study was carried out, the sample consisted of 252 students between 12 and 15 years of age from two educational centers in Lima. Sampling was by systematic selection of sample elements. Dental fluorosis was evaluated using the Dean Index. To determine the frequency and levels of dental fluorosis a clinical oral examination was carried out and a previously validated questionnaire was developed. Results: The frequency of dental fluorosis was 44.8% (n=113) affecting more males by 27.39% (n=69) and adolescents aged 13 years (15.1%). In relation to the levels of fluorosis, the "very mild" type predominated (34.9%). An association was also found between the presence and level of fluorosis with the number of fluoride applications (p<0.05). In addition, Dean's community fluorosis index was reported to be 0.43. Conclusions: In the school population evaluated, the frequency of fluorosis was 44.8% and the predominant level of fluorosis was very mild. In addition, the community index was 0.43, which indicated a borderline level of public health importance. Therefore, it can be considered that the number of topical fluoride applications received by the population without adequate planning could become a risk factor for causing dental fluorosis.

Anticaries potential of a fluoride foam

Abstract Foam has been used worldwide as a vehicle for the professional application of fluoride and hypothetically should have the same anticaries potential as conventional fluoride gel (F-gel) in terms of the formation of reaction products with enamel. Thus, the ability of Flúor Care® foam (FGM, Joinville, SC, Brazil, 12,300 ppm F, acidulated) to react with enamel was evaluated in comparison with Flúor gel® (DFL, Rio de Janeiro, RJ, Brazil, 12,300 ppm F, acidulated). Slabs (n=10/group) of sound enamel and with caries lesion were used, in which the concentrations of total fluoride (TF), and loosely (CaF2-like) and firmly (FAp) bound types were determined. The importance of agitation during application was previously tested. The determinations were made with fluoride ion-specific electrode and the results were expressed in μg F/cm² of the treated enamel area. ANOVA and Tukey tests were used to analyze the difference among treatments, independently for sound and carious enamel. The agitation of the products during application significantly increased the reactivity of the foam (p<0.05), but not that of the gel (p>0.05). The foam did not differ from F-gel (p>0.05) concerning the formation of TF and CaF2-like in sound or carious enamel. Regarding FAp, the foam did not differ from F-gel (p>0.05) in the carious enamel, but the concentration in the sound was lower (p<0.05). The results show that this commercial fluoride foam tested needs to be agitated during application to improve its reactivity with enamel, which raises a question about other brands.

Resumo A espuma tem sido utilizada mundialmente como veículo para aplicação profissional de fluoreto e hipoteticamente deveria ter o mesmo potencial anticárie que o gel fluoretado convencional (F-gel) em termos de formação de produtos de reação com o esmalte. Assim, a capacidade da espuma Flúor Care® (FGM, Joinville, SC, Brasil, 12.300 ppm F, acidulada) de reagir com o esmalte foi avaliada em comparação com o Flúor gel® (DFL, Rio de Janeiro, RJ, Brasil 12.300 ppm F, acidulado). Foram utilizados blocos (n=10/grupo) de esmalte hígido e com lesão de cárie, nos quais foram determinadas as concentrações de flúor total (FT), e os tipos de flúor fracamente (tipo-CaF2) e firmemente (FAp) ligados ao esmalte. A importância da agitação durante a aplicação foi previamente testada. As determinações foram feitas com eletrodo íon específico para fluoreto e os resultados foram expressos em μg F/cm² da área tratada do esmalte. A diferença entre os tratamentos foi analisada por ANOVA e Tukey (α=5%), independentemente para esmalte hígido e cariado. A agitação dos produtos durante a aplicação aumentou significativamente a reatividade da espuma (p<0,05), mas não a do gel (p>0,05). A espuma não diferiu do F-gel (p>0,05) quanto à formação de FT e tipo-CaF2 no esmalte hígido ou cariado. Em relação à FAp, a espuma não diferiu do F-gel (p>0,05) no esmalte cariado, mas a concentração no hígido foi menor (p<0,05). Os resultados mostram que esta espuma fluoretada comercial testada precisa ser agitada durante a aplicação para melhorar sua reatividade com o esmalte, o que levanta questão sobre outras marcas.

Effect of sodium fluoride on myocardial damage by regulating apoptosis through JNK signaling pathway / 环境与职业医学

Background It has been found that fluoride may cause cardiomyocyte damage. c-Jun N-terminal kinases (JNK) signaling pathway plays an important role in apoptosis, but its role in fluorosis-induced cardiomyocyte damage is still unknown yet. Objective To explore the toxic effect of sodium fluoride (NaF) on H9c2 cardiomyocytes of rats and whether NaF affects cardiomyocyte apoptosis through the JNK signaling pathway. Methods According to the concentrations of sodium fluoride and whether sp600125 (JNK inhibitor) was added, cardiomyocytes of rats were divided into six groups, including control group, SP600125 group (SP group), 0.24, 0.48, and 0.96 mmol·L−1 NaF groups, and 0.96 mmol·L−1 NaF+SP600125 group (NaF+SP group). Cardiomyocytes exposed to NaF for 24 h were observed using a fluorescence inverted microscope. The changes of cell viability at 24, 48, and 72 h after the treatment were detected by CCK-8 method. The levels of reactive oxygen species (ROS) at 24 h after the treatment in H9c2 cardiomyocytes were determined by fluorescent probe method. The expression levels of Bcl-2, Bax, Caspase-3, and JNK mRNA at 24 h after the treatment were detected by real-time PCR. The protein expression levels of Bcl-2, Bax, Caspase-3, and p-JNK at 24 h after the treatment were detected by Western blotting. Results Compared with the control group, after being exposed to 0.48 and 0.96 mmol·L−1 NaF for 24 h, the cell growth density decreased. With the increase of NaF concentration, rounded cells and some suspended dead cells appeared. At 24h after exposure to NaF, the cell viability of the 0.48 and 0.96 mmol·L−1 NaF groups decreased compared with the control group (P<0.05). At 48h and 72h after exposure to NaF, the cell viability levels of the NaF treated groups were significantly lower than that of the control group (P<0.05). After NaF exposure for 24 h, compared with the control group, the intracellular ROS levels were increased (P<0.05); the mRNA expression levels of Bcl-2 were decreased to varying degrees, especially in the 0.48 and 0.96 mmol·L−1 NaF groups (P<0.05); the mRNA expression levels of Bax, Caspase-3, and JNK were increased (P<0.05); the protein expression levels of Bcl-2 were reduced (P<0.05); the protein expression levels of Bax, Caspase-3, and p-JNK were elevated (P<0.05). Compared with the 0.96 mmol·L−1 NaF group, the cell viability of the NaF+SP group was increased, the intracellular ROS level was decreased, the mRNA expression levels of Bax, Caspase-3, and JNK were decreased, the protein expression level of Bcl-2 was increased, and the protein expression levels of Bax, Caspase-3, and p-JNK were decreased (P<0.05); the expression level of Bcl-2 mRNA had a rising trend but showed no statistical significance (P>0.05). Conclusion Cardiomyocyte damage after excessive fluoride exposure may result from fluoride inducing excessive ROS production in cardiomyocytes, which may activate the JNK signaling pathway and induce cardiomyocyte apoptosis.

Research progress on fluoride-releasing restorative materials for caries control / 口腔疾病防治

@#Restorative materials such as conventional glass ionomer cement (CGIC), resin-modified glass ionomer cement (RMGIC), polyacid-modified composite resin (compomer), and giomer have the properties of fluoride release and refill, which may prevent or slow down the progression of caries. The caries resistance of these materials was evaluated according to the following criteria: fluorine-releasing ability, antibacterial activity, mechanical properties and anti-aging properties. The anti-caries effect of these materials mainly depends on the effect of fluoride ions on mineralization. However, materials with strong fluorine release ability, such as CGIC, are mainly used in pediatric dentistry and temporary restoration due to their poor mechanical properties. It is difficult to achieve both fluoride ion release potential and mechanical strength, and there are few materials that can provide ideal mechanical strength while maintaining a high standard of fluoride release. The fluoride releasing and recharging capacity of CGIC, RMGIC, compomer and giomer decrease successively. The trend of material modification, to a certain extent, tends to sacrifice the fluoride release capacity of materials to maintain the ideal mechanical strength. In recent years, scholars have tried to add a variety of fillers to further enhance the anti-cracking ability of materials and add antibacterial agents to compensate for the anti-caries effect to reduce the loss of fluoride release.

Correlation analysis and benchmark dose study on bone metabolic biochemical index of low doses of exposed hydrogen fluoride workers / 中华劳动卫生职业病杂志

Objective: To analyze correlation of occupational hydrogen fluoride exposure to low doses of bone metabolism index through occupational epidemiological investigation and benchmark dose calculation. Methods: In May 2021, using cluster sampling method, 237 workers exposed to hydrogen fluoride in a company were selected as the contact group, and 83 workers not exposed to hydrogen fluoride in an electronics production company were selected as the control group. The external exposure dose and urinary fluoride concentration, blood and urine biochemical indicators of the workers was measured.The relationship between external dose and internal dose of hydrogen fluoride was analyzed. The external dose, urinary fluoride was used as exposure biomarkers, while serum osteocalcin (BGP), serum alkaline phosphatase (AKP) and urinary hydroxyproline (HYP) were used as effect biomarkers for bone metabolism of hydrogen fluoride exposure. The benchmark dose calculation software (BMDS1.3.2) was used to calculate benchmark dose (BMD) . Results: Urine fluoride concentration in the contact group was correlated with creatinine-adjusted urine fluoride concentration (r=0.69, P=0.001). There was no significant correlation between the external dose of hydrogen fluoride and urine fluoride in the contact group (r=0.03, P=0.132). The concentrations of urine fluoride in the contact group and the control group were (0.81±0.61) and (0.45±0.14) mg/L, respectively, and the difference between the two groups was statistically significant (t=5.01, P=0.025). Using BGP, AKP and HYP as effect indexes, the urinary BMDL-05 values were 1.28, 1.47 and 1.08 mg/L, respectively. Conclusion: Urinary fluoride can sensitively reflect the changes in the effect indexes of biochemical indexes of bone metabolism. BGP and HYP can be used as early sensitive effect indexes of occupational hydrogen fluoride exposure.

Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome / 生物医学与环境科学（英文）

OBJECTIVE@#Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).@*METHODS@#We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.@*RESULTS@#Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.@*CONCLUSION@#Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.

In vitro effect of low-fluoride toothpaste supplemented with sodium trimetaphosphate, xylitol, and erythritol on enamel demineralization

Abstract Regular use of toothpaste with fluoride (F) concentrations of ≥ 1000 ppm has been shown to contribute to reducing caries increment. However, when used by children during the period of dental development, it can lead to dental fluorosis. Objective: In this study, we aimed to evaluate the in vitro effect of a toothpaste formulation with reduced fluoride (F) concentration (200 ppm) supplemented with sodium trimetaphosphate (TMP: 0.2%), Xylitol (X:16%), and Erythritol (E: 4%) on dental enamel demineralization. Methodology: Bovine enamel blocks were selected according to initial surface hardness (SHi) and then divided into seven experimental toothpaste groups (n=12). These groups included 1) no F-TMP-X-E (Placebo); 2) 16% Xylitol and 4% Erythritol (X-E); 3) 16% Xylitol, 4% Erythritol and 0.2%TMP (X-E-TMP); 4) 200 ppm F (no X-E-TMP: (200F)); 5) 200 ppm F and 0.2% TMP (200F-TMP); 200 ppm F, 16% Xylitol, 4% Erythritol, and 0.2% TMP (200F-X-E-TMP); and 7) 1,100 ppm F (1100F). Blocks were individually treated 2×/day with slurries of toothpastes and subjected to a pH cycling regimen for five days (DES: 6 hours and RE: 18 hours). Then, the percentage of surface hardness loss (%SH), integrated loss of subsurface hardness (ΔKHN), fluoride (F), calcium (Ca), and phosphorus (P) in enamel were determined. The data were analyzed by ANOVA (1-criterion) and the Student-Newman-Keuls test (p<0.001). Results: We found that the 200F-X-E-TMP treatment reduced %SH by 43% compared to the 1100F treatments (p<0.001). The ΔKHN was ~ 65% higher with 200F-X-E-TMP compared to 1100F (p<0.001). The highest concentration of F in enamel was observed on the 1100F treatment (p<0.001). The 200F-X-E-TMP treatment promote higher increase of Ca and P concentration in the enamel (p<0.001). Conclusion: The association of 200F-X-E-TMP led to a significant increase of the protective effect on enamel demineralization compared to the 1100F toothpaste.

Evaluation of the remineralizing capacity of silver diamine fluoride on demineralized dentin under pH-cycling conditions

Abstract Objective (1) to determine the effects of the silver diamine fluoride (SDF) and sodium fluoride (NaF) in demineralized dentin exposed to an acid challenge by pH-cycling, (2) to evaluate the remineralizing capacity of SDF/NaF products based on the physicochemical and mechanical properties of the treated dentin surfaces. Methodology In total, 57 human molars were evaluated in different stages of the experimental period: sound dentin - negative control (Stage 1), demineralized dentin - positive control (Stage 2), and dentin treated with SDF/NaF products + pH-c (Stage 3). Several commercial products were used for the SDF treatment: Saforide, RivaStar, and Cariestop. The mineral composition and crystalline and morphological characteristics of the dentin samples from each experimental stage were evaluated by infrared spectroscopy (ATR-FTIR), X-ray diffraction, and electron microscopy (SEM-EDX) analytical techniques. Moreover, the mechanical response of the samples was analyzed by means of the three-point bending test. Statistics were estimated for ATR-FTIR variables by Wilcoxon test, while the mechanical data analyses were performed using Kruskal-Wallis and Mann Whitney U tests. Results Regarding the chemical composition, we observed a higher mineral/organic content in the SDF/NaF treated dentin + pH-c groups (Stage 3) than in the positive control groups (Saforide p=0.03; Cariestop p=0.008; RivaStar p=0.013; NaF p=0.04). The XRD results showed that the crystallite size of hydroxyapatite increased in the SDF/NaF treated dentin + pH-c groups (between +63% in RivaStar to +108% in Saforide), regarding the positive control. SEM images showed that after application of the SDF/NaF products a crystalline precipitate formed on the dentin surface and partially filled the dentin tubules. The flexural strength (MPa) values were higher in the dentin treated with SDF/NaF + pH-c (Stage 3) compared to the positive control groups (Saforide p=0.002; Cariestop p=0.04; RivaStar p=0.04; NaF p=0.02). Conclusions The application of SDF/NaF affected the physicochemical and mechanical properties of demineralized dentin. According to the results, the use of SFD/NaF had a remineralizing effect on the dentin surface even under acid challenge.

Effects of silver diamine fluoride on demineralization protection after a secondary acid challenge

Abstract Objective This investigation describes the effects of 5% sodium fluoride varnish and 38% silver diamine fluoride on demineralization protection of human enamel lesions of three different severities after a secondary acid challenge. Study design Specimens underwent color and enamel surface microhardness change measurements after demineralization and treatment events. Transverse microradiography was conducted following the secondary demineralization. Results After treatments, enamel surface microhardness change showed that 24-hour lesions treated with fluoride varnish had less rehardening than 24-hour lesions treated with silver diamine fluoride (p<0.05), whereas 144-hour lesions from both treatment groups showed a beneficial decrease in surface microhardness change that was markedly better in samples treated with silver diamine fluoride (p<0.05). After the secondary demineralization, 24- and 144-hour lesions treated with silver diamine fluoride showed a sustained beneficial decrease in enamel surface microhardness change when compared to fluoride varnish-treated samples of the corresponding lesion severity (p<0.05). Transverse microradiography showed no difference between fluoride varnish- and silver diamine fluoride-treated samples of any corresponding lesion severity, indicating that remineralization in both fluoride varnish- and silver diamine fluoride-treated samples was proportional to each other after a secondary acid challenge. Conclusions Using silver diamine fluoride may have comparable benefits to fluoride varnish in mineral loss prevention.

Success rate of silver nano-particles in comparison to silver diamine fluoride in management of deep carious lesions: a randomized controlled clinical trial / Taxa de sucesso de nanopartículas de prata em comparação ao fluoreto de diamina de prata no manejo de lesões cariosas profundas: um estudo clínico controlado randomizado

Objective: Evaluate the effectiveness of nanosilver fluoride in comparison to silver diamine fluoride in management of deep carious lesions. Material and Methods: This double-blinded randomized controlled clinical trial included thirty-six patients with deep carious mandibular molars. Patients were recruited form the outpatient clinic of Suez canal university, Egypt and randomly allocated into three groups, Nanosilver fluoride group, Silver diamine fluoride group and control group. For all groups, teeth were isolated by rubber dam. Access was done followed by partial caries removal. Silver diamine fluoride or Nanosilver fluoride were applied, and all teeth were restored with composite resin restorative. Patients were recalled after 3 and 6 months to follow-up the pulp vitality. R-statistical analysis software for Windows, version 4.1.1, was used to conduct the statistical analysis Results: At 3 month, for all groups, all teeth were successful. After 6 months, for silver diamine fluoride group, a single case failed. Regarding the nanosilver fluoride, all cases were successful. For the control group, two cases failed. No statistically significant difference was found between the tested groups. Conclusion: Application of 5% Nanosilver to fluoride varnish has similar clinical efficacy as silver diamine fluoride in arresting the dentin caries progression (AU)

Objetivo: Avaliar a eficácia de fluoreto de nanoprata em comparação ao fluoreto de diamina de prata no manejo de lesões profundas de cárie. Material e Métodos: Este estudo clínico controlado randomizado duplo-cego incluiu trinta e seis pacientes com lesões de cárie profunda em molares inferiores. Os pacientes foram recrutados no ambulatório da Universidade do Canal de Suez, no Egito, e alocados aleatoriamente em três grupos de tratamento: fluoreto de nanoprata, fluoreto de diamina de prata e grupo controle. Para todos os grupos, os dentes foram submetidos ao isolamento absoluto. O acesso à lesão foi feito seguido pela remoção parcial de tecido cariado. Tanto o fluoreto de diamina quanto fluoreto de nanoprata foram aplicados, e todos os dentes foram restaurados com resina composta. Os pacientes foram avaliados após 3 e 6 meses para o acompanhamento da vitalidade pulpar. O software estatístico R-statistical para Windows, versão 4.1.1, foi usado para as análises. Resultados: Em 3 meses, para todos os grupos, todos os dentes apresentaram sucesso no tratamento. Após 6 meses, para o grupo que utilizou o fluoreto de diamina de prata um único caso falhou. Em relação ao fluoreto de nanoprata, todos os casos apresentaram sucesso. Para o grupo controle, dois casos falharam. Não houve diferença estatística entre os grupos testados. Conclusão: A aplicação de verniz de fluoreto de nanoprata a 5% tem eficácia clínica semelhante ao fluoreto de diamina de prata na interrupção da progressão de cárie no tecido dentinário (AU)

Antibacterial Efficacy of Silver Diamine Fluoride Compared to Casein Phosphopeptide-Amorphous Calcium Phosphate Against Streptococcus mutans in a Biofilm Caries Model

ABSTRACT Objective: To compare the antibacterial efficacy of silver diamine fluoride (SDF) with a product containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) against Streptococcus mutans using a biofilm caries model. Material and Methods: Twenty-seven saliva-coated dentine blocks obtained from extracted human teeth were inoculated with Streptococcus mutans monospecies biofilm in this in vitro study. The biofilms were then exposed to 10% sucrose in brain heart infusion broth eight times daily for seven days. After the biofilm growth period, the dentine blocks (n=9 per group) were treated with one of the following substances: 1) sterile saline (control), 2) 38% SDF, and 3) a product containing CPP-ACP. Then, the samples were incubated at 37ºC for 48 hours, and the numbers of viable microorganisms in the biofilms were counted and compared. ANOVA and Tukey's HSD tests were used to analyze the data (p<0.05). Results: The number of viable bacteria, as determined by the number of colony-forming units (CFU mL-1) of Streptococcus mutans, was significantly reduced following treatment with SDF and the CPP-ACP product (p<0.05). However, SDF showed superior antibacterial activity compared to the CPP-ACP product (mean CFU mL-1 =zero compared to 96 x106) (p<0.05). Conclusion: SDF has higher antibacterial activity against cariogenic Streptococcus mutans biofilm than the CPP-ACP product. The CPP-ACP product showed antibacterial activity, but it was limited.

Fluorotic Enamel Susceptibility to Dental Erosion and Fluoride Treatment

Abstract The purpose of this in vitro study was to test the hypothesis that fluoride treatment can prevent dental erosion on fluorotic enamel of different severities. It followed a 3×2 factorial design, considering a) fluorosis severity: sound (TF0, Thylstrup-Fejerskov Index), mild (TF1-2), moderate (TF3-4); and b) fluoride treatment: 0 (negative control) and 1150ppmF. Human molars with the three fluorosis severities (n=16, each) were selected and randomly assigned to the two fluoride treatments (n=8). Enamel blocks (4×4mm) were prepared from each tooth and subjected to a dental erosion cycling model, for 10 days. The daily cycling protocol consisted of erosive challenges (1% citric acid, pH 2.4), interspersed by periods of immersion in artificial saliva, and three 2-minute treatments with either 0 or 1150ppm F. The enamel volume loss (mm3) was calculated by subtracting values obtained by microtomography before and after cycling. Two-Way ANOVA showed no significant interaction between fluorosis severity and fluoride treatment (p=0.691), and no significant effect for either fluorosis severity (TF0 mean±standard-deviation: 13.5(10-2±0.42(10-2, TF1-2: 1.50(10-2±0.52(10-2, TF3-4: 1.24(10-2±0.52(10-2, p=0.416) or treatment (0ppmF: 1.49(10-2±0.53(10-2; 1150ppmF: 1.21(10-2±0.42(10-2; p=0.093), when evaluated independently. Considering the limitations of this in vitro study, the presence and severity of fluorosis in enamel do not appear to affect its susceptibility to dental erosion. Fluoride treatment was not effective in preventing the development of dental erosion in both sound and fluorotic enamel substrates under our experimental conditions.

Resumo Este estudo in vitro foi testou a hipótese de que o tratamento com flúor pode prevenir a erosão dentária no esmalte fluorótico de diferentes severidades. O objetivo deste estudo foi: investigar o efeito protetor dos fluoretos contra a erosão e abrasão simuladas no esmalte fluorótico. Seguiu um desenho fatorial 3×2, considerando a) severidade da fluorose em 3 níveis: hígido (TF0, Índice Thylstrup-Fejerskov), suave (TF1-2), moderada (TF3-4); b) tratamento com flúor: 0 (controle negativo) e 1150ppmF. Molares humanos com as três severidades de fluorose (n=16, cada) foram selecionados e distribuídos aleatoriamente para os dois tratamentos com flúor (n=8). Blocos de esmalte (4×4mm) foram preparados a partir de cada dente e submetidos a um modelo de ciclo de erosão dentária, por 10 dias. O protocolo de ciclagem diária consistiu em seis desafios erosivos de 5 minutos (1% de ácido cítrico, pH 2,4), intercalados por seis períodos de imersão em saliva artificial e três tratamentos de 2 minutos com 0 ou 1150ppmF. O volume do esmalte perdido foi calculado subtraindo o perfil superficial 3D obtido por microtomografia antes e depois da ciclagem. A ANOVA de dois fatores não mostrou interação significativa entre a severidade da fluorose e o tratamento com flúor (p = 0,691) e nenhum efeito significativo para a severidade da fluorose (TF0 média+/desvio padrão: 13,5(10-2±0,42(10-2, TF1-2: 1,50(10-2±0,52(10-2, TF3-4: 1,24(10-2±0,52(10-2, p=0,416) ou tratamento (0: 1,49(10-2±0,53(10-2; 1150ppmF: 1,21(10-2±0,42(10-2, p=0,093), quando avaliados independentemente. Considerando as limitações deste estudo in vitro, a presença e severidade da fluorose no esmalte não parece afetar sua suscetibilidade à erosão dentária. O tratamento com flúor não foi eficaz na prevenção do desenvolvimento da erosão dentária em esmalte hígido e fluorótico, sob as condições experimentais utilizadas.

Dentifrício de alta concentração de fluoreto no controle da doença cárie: uma revisão integrativa / High fluoride concentration toothing for the control of caries disease: an integrative review / Dentición con alta concentración de fluoruro para el control de la enfermedad de caries: una revisión integrativa

INTRODUÇÃO: A cárie dentária é uma doença de caráter multifatorial, infecciosa, dieta dependente e resultado de um processo crônico, sendo considerada um problema de saúde pública. Os dentifrícios de alta concentração de flúor (5.000ppm), vem sendo recomendados para pacientes com alto risco de desenvolvimento da doença. OBJETIVO: Verificar o nível de evidência científica encontrada na literatura que indique o papel dos dentifrícios de alta concentração no controle da doença cárie, assim como, analisar em qual população seu uso é indicado e a presença de possíveis efeitos adversos. METODOLOGIA: Trata-se de uma revisão integrativa da literatura, com busca feita nas bases de dados PubMed e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), utilizando a seguinte combinação: "dentifrices" "AND" "high fluoride" "AND" "dental caries". RESULTADOS: Foram identificados 381 estudos, os quais foram atribuídos aos critérios de inclusão e exclusão, totalizando um total de 09 artigos que compuseram este estudo após a análise. CONCLUSÃO: Foi possível perceber um elevado nível de evidência científica, apesar da falta de padronização de estratégias metodológicas. Foi observado, a ausência de efeitos adversos relatados e uma importante contribuição do dentifrício de alta concentração para controle da doença cárie, sobretudo em pacientes adolescentes, idosos, irradiados e com alto risco de desenvolvimento da doença.

INTRODUCTION: Dental caries is a multifactorial, infectious, diet- dependent disease resulting from a chronic process and is considered a public health problem. A high-fluoride toothpaste (5,000ppm) have been recommended for patients at high risk of developing the disease. OBJECTIVE: To find the level of scientific evidence in the literature that indicates the role of high-fluoride dentifrices in the control of caries disease and to analyze in which population its use is indicated and the possibles adverse effects. METHODOLOGY: This is an integrative review, with a search performed in PubMed and Latin American and Caribbean Literature in Health Sciences (LILACS) databases, using the following combination: dentifrices AND high fluoride AND dental caries. RESULTS: 381 studies were identified, which were assigned to the inclusion and exclusion criteria. A total of 09 articles were selected for this integrative review. CONCLUSION: It was possible to realize a high level of scientific evidence, despite the lack of standardization of methodological strategies. It was observed the absence of reported adverse effects and an important contribution of the high-fluoride dentifrice to control dental caries, especially in adolescent, elderly, irradiated patients and at high risk of developing the disease.

INTRODUCCIÓN: La caries dental es una enfermedad multifactorial, infecciosa, dependiente de la dieta, resultante de un proceso crónico considerada un problema de salud pública. Se han recomendado pastas dentales con alta concentración de flúor (5.000 ppm) para pacientes con alto riesgo de desarrollar la enfermedad. OBJETIVO: Verificar el nivel de evidencia científica encontrada en la literatura que indica el papel de los dentífricos de alta concentración en el control de la enfermedad de caries, así como analizar en qué población está indicado su uso y la presencia de posibles efectos adversos. METODOLOGÍA: Esta es una revisión bibliográfica integradora, con una búsqueda realizada en las bases de datos PubMed y Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS), utilizando la siguiente combinación: "dentífricos" "AND" "high fluoride" "AND" "dental caries". RESULTADOS: Se identificaron 381 estudios, que fueron asignados a los criterios de inclusión y exclusión, totalizando un total de 09 artículos que integraron este estudio después del análisis. CONCLUSIÓN: Fue posible percibir un alto nivel de evidencia científica, a pesar de la falta de estandarización de las estrategias metodológicas. Se observó la ausencia de efectos adversos informados y una contribución importante del dentífrico de alta concentración para el control de la enfermedad de caries, especialmente en pacientes adolescentes, ancianos, irradiados y con alto riesgo de desarrollar la enfermedad.

Effects of different toothpaste formulations on erosive tooth wear prevention: systematic review / Efeitos de diferentes dentifrícios na prevenção do desgaste dentário erosivo: revisão sistemática de literatura

Objective: erosive tooth wear is a multifactorial condition that results in loss of dental hard tissue, caused by a chemical and mechanical process. This paper aims to carry out a systematic review presenting the effects of different toothpaste formulations on the loss of dental enamel surface in vitro. Material and Methods: the searches were performed in the databases PubMed, Web of Science, LILACS and Scielo. Articles published from 2010 to 2020 were filtered, without language restriction. Articles that included abrasion and erosion protocols were searched, as they were more similar to clinical reality, since toothpaste is applied through tooth brushing. The searches with descriptors and free terms on the topic resulted in 992 articles, however only 12 were within the search criteria. Results: the selected studies appointed that association of conventional fluorides (NaF) with metallic fluorides can be a promising strategy for the reduction of surface loss by erosive tooth wear. Toothpastes containing sodium fluoride, as well as tin without chitosan, showed a reduction in surface loss, considered sufficient for individuals with medium exposure to acids. In children's toothpastes, the one containing sodium fluoride showed a reduction in surface loss when compared to non-fluoride dentifrices. Conclusion: different protocols may result in less or greater loss of enamel surface, and methodological differences should be considered. To clarify the effects of dentifrices on erosive tooth wear, other properties of dentifrices should be investigated. (AU)

Objetivo: o desgaste erosivo é uma condição multifatorial que resulta em perda de tecido duro dentário, causado por um processo químico e mecânico. Este trabalho tem como objetivo realizar uma revisão sistemática de literatura apresentando os efeitos de diferentes formulações de dentifrícios na perda de superfície de esmalte dentário in vitro. Material e Métodos: a busca foi realizada nas bases de dados PubMed, Web of Science, LILACS e Scielo. Foram filtrados artigos publicados no intervalo de 2010 a 2020, sem restrição de idioma. Buscou-se artigos que incluíssem protocolos de abrasão e erosão, por mais se assemelhar a realidade clínica, uma vez que o dentifrício é aplicado através da escovação dentária. A busca com descritores e termos livres sobre o tema encontrou 992 artigos, entretanto somente 12 estavam dentro dos critérios da pesquisa. Resultados: os estudos selecionados apontaram que associação dos fluoretos convencionais (NaF) com os metálicos pode ser uma estratégia promissora para a redução de perda de superfície pelo desgaste dentário erosivo. Dentifrícios contendo fluoreto de sódio, assim como estanho sem quitosana, apresentaram redução na perda de superfície, sendo considerada suficiente para indivíduos com exposição média aos ácidos. Em dentifrícios infantis, aquele que continha fluoreto de sódio apresentou uma redução de perda de superfície quando comparado com dentifrícios sem fluoreto. Conclusão:diferentes protocolos podem resultar em menor ou maior perda de superfície de esmalte e as diferenças (AU)

Metabolic effect of low fluoride levels in the islets of NOD mice: integrative morphological, immunohistochemical, and proteomic analyses

Abstract Fluoride (F) has been widely used to control dental caries, and studies suggest beneficial effects against diabetes when a low dose of F is added to the drinking water (10 mgF/L). Objectives This study evaluated metabolic changes in pancreatic islets of NOD mice exposed to low doses of F and the main pathways altered by the treatment. Methodology In total, 42 female NOD mice were randomly divided into two groups, considering the concentration of F administered in the drinking water for 14 weeks: 0 or 10 mgF/L. After the experimental period, the pancreas was collected for morphological and immunohistochemical analysis, and the islets for proteomic analysis. Results In the morphological and immunohistochemical analysis, no significant differences were found in the percentage of cells labelled for insulin, glucagon, and acetylated histone H3, although the treated group had higher percentages than the control group. Moreover, no significant differences were found for the mean percentages of pancreatic areas occupied by islets and for the pancreatic inflammatory infiltrate between the control and treated groups. Proteomic analysis showed large increases in histones H3 and, to a lesser extent, in histone acetyltransferases, concomitant with a decrease in enzymes involved in the formation of acetyl-CoA, besides many changes in proteins involved in several metabolic pathways, especially energy metabolism. The conjunction analysis of these data showed an attempt by the organism to maintain protein synthesis in the islets, even with the dramatic changes in energy metabolism. Conclusion Our data suggests epigenetic alterations in the islets of NOD mice exposed to F levels comparable to those found in public supply water consumed by humans.