Fluorosis dental en la primera infancia: estado del arte

La fluorosis dental se caracteriza por una hipomineralización de la estructura dental causada por ingesta excesiva de flúor sistémico. En la dentición decidua, su diagnóstico precoz es importante, dado que será un predictor para la aparición de lesiones en la dentición permanente. El objetivo de esta revisión fue describir la evidencia científica sobre la fluorosis dental en dentición decidua reportando su etiología y factores relacionados, prevalencia, diagnóstico y tratamiento. Se realizaron búsquedas electrónicas en las bases de datos Pub-Med/Medline, EbscoHost y ScienceDirect (noviembre/2020), utilizando las palabras clave "dental fluorosis", "deciduous teeth", "primary tooth", "primary teeth". El desarrollo de fluorosis dental en dentición decidua se relacionó con la ingesta de múltiples fuentes de flúor principalmente, agua potable, alimentos de la dieta, fórmulas infantiles, suplementos y uso de dentífricos fluorados en dosis inadecuadas. Algunos factores prenatales, como vivir en terrenos montañosos o de gran altitud y habitar en lugares cercanos a minas de combustión de carbón, también fueron asociados. La prevalencia de fluorosis dental reportada en los estudios varió entre 6,2 y 96,6 %, dependiendo principalmente de la concentración de flúor en agua potable. Para el diagnóstico de la fluorosis dental en la dentición decidua se deben considerar características como la localización, aspecto, extensión y color de la lesión, realizando diagnóstico diferencial con otro tipo de defectos en esmalte y dentina. Así mismo, el tratamiento de las lesiones dependerá de la severidad del defecto y condiciones individuales del paciente.

Dental fluorosis is characterized by a hypomineralization of the tooth structure caused by excessive intake of systemic fluoride. In the deciduous dentition, its early diagnosis is important since it will be a predictor for the appearance of lesions in the permanent dentition. The objective of this review was to describe the scientific evidence on dental fluorosis in deciduous dentition, reporting its etiology and related factors, prevalence, diagnosis and treatment. Electronic searches were conducted PubMed / Medline, EbscoHost and ScienceDirect (November / 2020) databases, using the keywords "dental fluorosis", "deciduous teeth", "primary tooth", "primary teeth". The development of Dental fluorosis in deciduous dentition was related to the intake of multiple sources of fluoride mainly; drinking water, diet foods, infant formulas, supplements and the use of luoridated toothpastes in inadequate doses. Some prenatal factors such as living in mountainous or high altitude terrain and living in places near coal-burning mines were also associated. The prevalence of dental fluorosis in early childhood reported in the studies varied between 6.2% and 96.6%, depending mainly on the concentration of fluoride in drinking water. For the diagnosis of dental fluorosis in the deciduous dentition, characteristics such as the location, appearance, extension and color of the lesion must be considered, making a differential diagnosis with other types of enamel and dentin defects. Evenly, the treatment of lesions will depend on the severity defects and individual patient conditions.

Glutathione S-transferase genetic polymorphisms and fluoride-induced reproductive toxicity in men with idiopathic infertility / 亚洲男科学杂志(英文版)

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.

Análisis curricular de la enseñanza aprendizaje del flúor en la disciplina Estomatología General

Introducción: La enseñanza-aprendizaje de los métodos de prevención y control de la caries dental en estomatología requiere de una formación académica que implique el conocimiento y desarrollo de habilidades del uso del flúor. Objetivo: Analizar la contribución de los programas de las asignaturas de la disciplina Estomatología General del plan de estudio E de la carrera Estomatología a la sistematización en la enseñanza-aprendizaje del flúor. Métodos: Se realizó una investigación cualitativa mediante revisión de documentos curriculares de la carrera y programas de las asignaturas de la disciplina Estomatología General del plan de estudio E. Se analizaron los temas, contenidos, objetivos y sistemas de habilidades, orientaciones metodológicas y estrategias curriculares de los programas y su relación con la enseñanza aprendizaje del flúor. Resultados: Las ocho asignaturas que contribuyen al aprendizaje del flúor abarcan todos los años de la carrera, más de la mitad abordan de manera directa este contenido, en tres sus vínculos son indirectos y no se aborda dentro de los contenidos o habilidades en el programa. El sistema de conocimientos y sistema de habilidades, seguido de los objetivos, resultó ser donde más se plantea la enseñanza del flúor. Solo dos asignaturas lo abordan en las orientaciones metodológicas. Conclusiones: La estructura del diseño curricular posibilita el enfoque en sistema de la enseñanza-aprendizaje del flúor, sin embargo, no existe una estrategia de la disciplina que garantice la sistematización del conocimiento de las acciones preventivas y curativas.

Introduction: The teaching-learning process of methods for the prevention and control of dental caries in dentistry requires academic training that involves knowledge and development of skills in the use of fluoride. Objective: To analyze the contribution of the programs of the subjects of General Dentistry discipline in the Plan E of Dentistry career to the systematic teaching and learning process of the use of fluoride. Methods: A qualitative research was carried out by revising curricular documents of the studies and programs of the subjects of General Dentistry discipline of Plan E. Themes, contents, objectives and systems of abilities, methodological orientations and curricular strategies of the programs were analyzed as well as their relationship with the teaching-learning process of the use of fluoride. Results: The eight subjects that contribute to the leaning of the use of fluoride cover all the academic years of the dental studies. More than half of the subjects directly considers this topic in their programs. Three of the subjects has indirect approach of the topic in question, and it is not taught in the content or abilities in the program. The teaching of the use of fluoride was emphasized in the knowledge system and system of abilities, followed by the objective. It was only covered in two subjects, in the methodological orientations. Conclusions: The structure of the curricular design makes possible the system approach of the teaching-learning process of the use of fluoride. Unfortunately, there is no a strategy of the discipline that guarantees systematization of the knowledge of preventive and healing actions.

Fluoride in Mozambique: retrospective study / Flúor em Moçambique: estudo retrospectivo

ABSTRACT Objective: The study aims to analyse the fluoride concentration in the water supply of the capital of each province of Mozambique, 2019 and compare with previous data 1978 and 2008. Methods: The water supply in cities of Mozambique were analysed in 1978, 2008 and 2019 and water from Tete's River in 1978 and 2019. The fluoride concentration of the water samples was determined in duplicate, using the ion-sensitive electrode (Orion 9609), coupled to a potentiometer (Procyon, model 720), adopting a significance level of 5%. Results: The average fluoride concentration found in the years 1978, 2008 and 2019 was 0.31, 0.33 and 0.14 mg F/L, respectively. The fluoride concentrations collected from household taps in 1978, 2008 and 2019 were: Cabo Delgado/Pemba (0.62, 0.28 and 0.07 mg F/L), Niassa/Lichinga (0.18, 0.98 and 0.07 mg F/L), Nampula/Nampula (0.18, 0.01 and 0.06 mg F/L), Zambézia/Quelimane (0.81, 0.37 and 0.15 mg F/L), Tete/Tete (1.00, 0.97 and 0 .46 mg F/L), Sofala/Beira (0.00, 0.01 and 0.10mg F/L), Manica/Chimoio (0.04, 0.01 and 0.07 mg F/L), Inhambane/Inhambane (0.00, 0.05 and 0.19 mg F/L), Gaza/Xai-Xai (0.01, 0.06 and 0.06 mg F/L) and Maputo (0.23, 0.36 and 0.23 mg F/L), respectively. In the waters of the Zambeze River was 5.5 mg F/L in 1978 and 0.12 mg F/L in 2019. There was no significant change between the fluoride concentrations in the water collected from the taps during the periods studied (p=0.83), however there was a significant difference in the water collected from the river (p<0.05). Conclusion: Tete' River showed a significant reduction in fluoride concentration, and in the piped water collected in all municipalities, the fluoride content was below optimum.

RESUMO Objetivo: O estudo visa analisar a concentração de flúor no abastecimento de água da capital de cada província de Moçambique, 2019 e comparar com dados anteriores de 1978 e 2008. Métodos: A água de abastecimento das cidades de Moçambique foi analisada em 1978, 2008 e 2019 e a água do Rio Tete em 1978 e 2019. A concentração de flúor das amostras de água foi determinada em duplicata, utilizando o eletrodo íon-sensível (Orion 9609), acoplado a um potenciômetro (Procyon, modelo 720), adotando-se nível de significância de 5%. Resultados: A concentração média de flúor encontrada nos anos de 1978, 2008 e 2019 foi de 0,31, 0,33 e 0,14 mg F/L, respectivamente. As concentrações de flúor recolhidas nas torneiras das casas em 1978, 2008 e 2019 foram: Cabo Delgado/Pemba (0,62, 0,28 e 0,07 mg F/L), Niassa/Lichinga (0,18, 0,98 e 0,07 mg F/L), Nampula/Nampula (0,18, 0,01 e 0,06 mg F/L), Zambézia /Quelimane (0,81, 0,37 e 0,15 mg F/L), Tete/Tete (1,00, 0,97 e 0,46 mg F/L), Sofala/Beira (0,00, 0,01 e 0,10 mg F/L), Manica/Chimoio (0,04, 0,01 e 0,07 mg F/L), Inhambane/Inhambane (0,00 , 0,05 e 0,19 mg F/L), Gaza/Xai-Xai (0,01, 0,06 e 0,06 mg F/L) e Maputo (0,23, 0,36 e 0,23 mg F/L), respectivamente. Nas águas do rio Zambeze foi de 5,5 mg F/L em 1978 e 0,12 mg F/L em 2019. Não houve alteração significativa entre as concentrações de flúor na água coletada das torneiras durante os períodos estudados (p=0,83), porém houve diferença significativa na água captada no Rio (p<0,05). Conclusão: O Rio Tete apresentou redução significativa na concentração de flúor, e na água das torneiras coletada em todas as cidades, o teor de flúor estava abaixo do ideal.

Automatic radiolabeling of the norepinephrine transporter targeted tracer 18F-mFBG and evaluation of 18F-mFBG PET/CT imaging in pheochromocytoma / 中华核医学与分子影像杂志

Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.

Research progress on isotope-exchange-based 18F-labeling methods / 中华核医学与分子影像杂志

The application of isotope exchange can realize radiolabeling in partially aqueous media, proceed under mild reaction conditions, and exclude complex purification procedure. It is suitable for one-step labeling of sensitive biomolecules with clinical application potential. This review systematically introduces the 18F/ 19F isotope exchange reactions based on carbon and those non-carbon-based reaction centers including silicon, boron, phosphorus, sulfur, gallium and iron. Discussions of the effects on isotope exchange radiochemical yields and molar activities by different reaction types, and labeling conditions and substitute groups on classic labeled substrate are held where possible, as well as recent applications in using these methodologies to develop PET probes.

Evaluation of the effect of linker on novel targeted PSMA PET probe / 中华核医学与分子影像杂志

Objective:To prepare a novel targeted prostate specific membrane antigen (PSMA) molecular probe Al 18F-PSMA-136, and evaluate the effects of the change in linker on the biological behavior and tumor targeting ability. Methods:Al 18F-PSMA-136 was prepared by replacing the phenyl of Al 18F-PSMA-137 with cyclohexyl in 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA). The inhibition abilities of PSMA of NOTA-PSMA-136 and NOTA-PSMA-137 were determined by N-acetylated-α-linked acidic dipeptidase (NAALADase) method. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio-high-performance liquid chromatography. The PSMA specificity and tumor targeting capability of the probes were investigated in 22Rv1 (PSMA positive-expressing) cells and mouse models. Independent-sample t test was used to analyze the data. Results:The Ki values of NOTA-PSMA-136 and NOTA-PSMA-137 were 3.41 and 0.30 nmol/L, respectively. The labeling yield of Al 18F-PSMA-136 was (30.1±8.4)% and the specific activity was (18.7±5.3) GBq/μmol. The radiochemical purities of the two probes were both greater than 95% and the stabilities in vitro were both good. Both probes showed PSMA-specific in 22Rv1 cells, but the uptake of Al 18F-PSMA-137 was significantly higher than that of Al 18F-PSMA-136 (1 h: (1.67±0.24) vs (1.00±0.01) percentage injected activity per 1×10 5 cells (%IA/1×10 5 cells): t=4.78, P=0.003; 2 h: (2.11±0.06) vs (1.03±0.06) %IA/1×10 5 cells; t=19.90, P<0.001). MicroPET/CT imaging showed that Al 18F-PSMA-136 and Al 18F-PSMA-137 had similar distribution in vivo, mainly concentrated in kidneys, intestine, gallbladder, bladder and tumor. However, the uptake of Al 18F-PSMA-137 in tumor was significantly higher than that of Al 18F-PSMA-136 (1 h: 1.78±0.10 vs 0.54±0.08; t=13.29, P<0.001; 2 h: 1.95±0.01 vs 0.52±0.11; t=18.53, P<0.001). Conclusion:Changes in the NOTA-conjugated linker can significantly affect the PSMA inhibition ability and tumor targeting, and the imaging effect of Al 18F-PSMA-137 with strong lipophilicity is superior.

Optimization of labeling methods for a novel prostate cancer PET probe Al 18F-PSMA-137 / 中华核医学与分子影像杂志

Objective:To investigate the effects of different labeling conditions on the yield of Al 18F-labeled 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA)-prostate specific membrane antigen (PSMA)-137, and to determine the experimental condition for obtaining Al 18F-PSMA-137 probe in high yield. Methods:The effects of different pH values, buffer systems (acetic acid-sodium acetate buffer system and potassium hydrogen phthalate (KHP) buffer system), AlCl 3-ligand ratios, ligand amounts, ethanol volumes and reaction temperatures on the labeling rate were investigated in detail. Results:The pH value of the reaction solution had a significant effect on the labeling rate, and the optimal range was 4.0-4.5. When the pH value was higher than 4.5, the labeling rate decreased significantly. Both the acetic acid-sodium acetate buffer system and the KHP buffer system could be used to label NOTA-PSMA-137 with Al 18F, and the KHP buffer system obtained higher labeling rate. The ratio of AlCl 3-ligand affected the labeling rate, and the highest labeling rate could be obtained when the ratio of AlCl 3-ligand was 0.54-0.62. When the ratio of AlCl 3-ligand was fixed, increasing the amount of ligand could improve the labeling yield. Adding hydrophilic organic solvent ethanol to the reaction system could significantly increase yield, with the highest labeling rate being achieved at a volume of 100 μl ethanol. The most suitable reaction temperature was 100 ℃, and when the temperature raised to 110 ℃, the labeling rate decreased significantly. The most suitable labeling conditions for NOTA-PSMA-137 were as following: 25 μl KHP buffer (0.50 mol/L, pH=4.0), 7.0 μl AlCl 3 solution (20 mmol/L), 200 μl Na 18F solution (74-80 MBq) and 230 μg ligand NOTA-PSMA-137 were mixed in a vial, then stood for 5 min and 100 μl ethanol was added, and all reagents were heated at 100 ℃ for 10 min. The yield of Al 18F-PSMA-137 under above conditions were 85.7%-88.5%. Conclusion:Optimization of labeling condition can improve the yield of Al 18F-PSMA-137 and the stability of the labeling.

Distribution characteristics and health risk assessment of elements in drinking water from endemic fluorosis areas with water improvement in Xi'an City / 中华地方病学杂志

Objective:To analyze the types and distribution characteristics of elements in drinking water from endemic fluorosis areas with water improvement in Xi'an City, understand the relationship between fluoride and various elements, and conduct health risk assessment on potential high-risk elements.Methods:From May to June 2017, one endemic fluorosis area with water improvement (Gaoling District, Huyi District, Lintong District) was selected according to the northeast, the southwest and the due east directions of Xi'an City as the survey area. Sixteen endemic fluorosis villages were selected from each endemic area, and 2 water samples were collected from each endemic village to detect fluoride and 12 elements such as chromium, manganese, ferrum, copper, zinc, arsenic, selenium, molybdenum, cadmium, antimony, barium, and lead. Hygienic evaluation was conducted according to national standards, and the potential high-risk elements (arsenic, molybdenum) were assessed for health risk through the health risk assessment model recommended by the National Environmental Protection Agency of the United States.Results:The water samples from the endemic fluorosis areas in Xi'an City mainly contained seven elements: barium, ferrum, molybdenum, arsenic, zinc, manganese, and chromium. The content of copper and selenium was relatively low, while the content of cadmium, antimony, and lead was extremely low. The fluoride content in water samples from Gaoling District and Lintong District was relatively high, and the fluorine, arsenic, molybdenum elements was pairwise positively correlated ( P < 0.05). The molybdenum element in water samples from Lintong District exceeded 9.38% (3/32). The fluoride in the water samples of Huyi District was relatively low, and the arsenic, molybdenum elements was positively correlated ( r = 0.84, P < 0.001), and the arsenic element exceeded the standard by 25.00% (8/32). The main health risk of drinking water in endemic fluorosis areas with water improvement in Xi'an City was arsenic exposure, with children at a higher risk than adults, and the areas of Huyi District, Lintong District, and Gaoling District declined, the risk of cancer (CR) of Gaoling District was < 10 -4 and hazard quotient (HQ) was < 1. However, in the areas of Huyi District and Lintong District (except HQ of adults), there was a higher risk (CR > 10 -4, HQ > 1). Children in one endemic fluorosis village in Lintong District had a higher non carcinogenic risk of molybdenum (HQ > 1). Conclusions:The drinking water in endemic fluorosis areas with water improvement in Xi'an City mainly contains 7 elements, especially arsenic and molybdenum, which need to be regularly monitored. Some areas have high health risks of arsenic in water, and monitoring, management, and related epidemiological investigations need to be strengthened. At the same time, it is necessary to actively monitor other toxic and harmful substances that may be introduced during the water improvement process to prevent the occurrence of secondary health problems.

Progress in the effect of fluorosis on skeletal muscle and its related molecular mechanisms / 中华地方病学杂志

Fluoride has dual health effects. Proper amount of fluoride plays an important role in bone development, prevention of dental caries and nervous system activity. Excessive fluoride causes chronic systemic diseases with dental fluorosis and skeletal fluorosis as the main symptoms. Fluorosis causes morphological and structural changes and function damage in skeletal muscle. Low concentration of fluoride induces muscle canal hypertrophy in skeletal muscle, while high concentration of fluoride leads to skeletal muscle atrophy by causing a series of signal pathway abnormalities. Abnormal changes in phosphatidylinositol-3-hydroxykinase/protein kinase B (PI3K/Akt) signal pathway, oxidative stress, and ubiquitin-proteasome pathway all play important roles in skeletal muscle injury caused by fluorosis. In this paper, the effect of fluoride on skeletal muscle and its related molecular mechanisms are reviewed.

Changes of serum CTX-1 and P1NP in patients with skeletal fluorosis in tea-drinking-borne endemic fluorosis area in Qinghai Province / 中华地方病学杂志

Objective:To observe the changes of serum C-terminal peptide of type Ⅰ collagen (CTX-1) and N-terminal lengthening peptide of type Ⅰ collagen (P1NP) in adult patients with skeletal fluorosis in the tea-drinking-borne endemic fluorosis area in Qinghai Province, and to find sensitive indicators for diagnosis of skeletal fluorosis.Methods:From April to August 2019, a case-control study was carried out in tea-drinking-borne endemic fluorosis area in Zhiduo County, Yushu Tibetan Autonomous Prefecture, and Gangcha County, Haibei Tibetan Autonomous Prefecture of Qinghai Province. According to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008), the clinical diagnosis and X-ray examination of skeletal fluorosis were carried out for permanent residents ≥25 years old and living for more than 10 years in the area, combined with face-to-face inquiry and investigation of past disease history, lifestyle and clinical manifestations. The patients with skeletal fluorosis and healthy people were selected as skeletal fluorosis group and control group, respectively. Randomized urine samples and fasting venous blood from the two groups were collected. The content of fluoride in urine was determined by ion selective electrode method, and the contents of CTX-1 and P1NP in serum were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 127 people in the disease area were investigated, including 63 cases in skeletal fluorosis group and 64 cases in control group. There was no statistically significant difference in age and sex ratio between the two groups ( t = 0.42, χ 2 = 0.07, P > 0.05). The X-ray examination results showed that the patients with skeletal fluorosis were mainly mild, accounting for 71.43% (45/63); X-ray changes were mainly ossification of interosseous membrane and tendon. The urinary fluoride in control group and skeletal fluorosis group was 1.62 (1.12, 1.95) and 3.22 (2.38, 4.89) mg/L, respectively, with statistically significant difference between the two groups ( Z = 7.07, P < 0.001). The difference of serum CTX-1 and P1NP contents between the two groups was statistically significant ( Z = 2.00, 4.89, P < 0.05). Conclusions:The levels of serum CTX-1 and P1NP in patients with skeletal fluorosis are higher than those in healthy people. Serum CTX-1 and P1NP may be used as sensitive indicators for diagnosis of skeletal fluorosis.

Effects of fluoride exposure on autophagy and AMPK/mTOR/ULK1 pathway in NG108-15 cells / 中华地方病学杂志

Objective:To investigate the effects of fluoride exposure on autophagy and the expression levels of adenosine monophosphate activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Unc-51-like kinase 1 (ULK1) in mouse neuroblastoma and rat glioma fusion cells (NG108-15 cells).Methods:NG108-15 cells were cultured in vitro and divided into control group (0 mg/L), low fluoride group (20 mg/L), medium fluoride group (40 mg/L) and high fluoride group (80 mg/L) according to the final concentration of sodium fluoride, and the cells were collected after 24 h of treatment for standby. NG108-15 cells autophagy was detected by immunofluorescence/immunocytochemistry (IF/ICC method, the autophagy positive control group was treated with chloroquine phosphate); the mRNA expression levels of AMPK, mTOR and ULK1 in each group were detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR); the protein expression levels of autophagy related protein microtubule-associated protein 1 light chain 3B (LC3B), AMPK, mTOR, ULK1, phosphorylation (p)-AMPK, p-mTOR, p-ULK1 in each group were detected by Western blotting. Results:No autophagosome was detected in the control group, and autophagosomes were detected in all the fluoride groups. The protein expression level of LC3B in the low, medium and high fluoride groups (1.80 ± 0.59, 2.16 ± 0.60, 2.30 ± 0.57) was significantly higher than that in the control group (1.00 ± 0.29, P < 0.05). The results of qRT-PCR showed that compared with the control group, the mRNA expression levels of AMPK in medium and high fluoride groups were higher (2.30 ± 0.57, 4.41 ± 1.05 vs 1.00 ± 0.01, P < 0.05); the mRNA expression levels of mTOR in the low, medium and high fluoride groups were lower (0.79 ± 0.04, 0.76 ± 0.09, 0.64 ± 0.10 vs 1.00 ± 0.01, P < 0.05), and the mRNA expression levels of ULK1 were higher (1.81 ± 0.39, 1.96 ± 0.35, 4.22 ± 1.03 vs 1.00 ± 0.01, P < 0.05). The results of Western blotting showed that compared with the control group, the protein expression levels of AMPK (1.21 ± 0.05, 1.20 ± 0.04, 1.30 ± 0.07 vs 1.00 ± 0.03), p-AMPK (1.12 ± 0.05, 1.20 ± 0.06, 1.49 ± 0.07 vs 1.00 ± 0.02), ULK1 (1.16 ± 0.05, 1.26 ± 0.05, 1.15 ± 0.05 vs 1.00 ± 0.04) and p-ULK1 (1.19 ± 0.04, 1.17 ± 0.02, 1.24 ± 0.05 vs 1.00 ± 0.05) in the low, medium and high fluoride groups were higher ( P < 0.05), and the protein expression levels of mTOR were lower (0.77 ± 0.03, 0.60 ± 0.03, 0.55 ± 0.04 vs 1.00 ± 0.04, P < 0.05); the protein expression levels of p-mTOR in the medium and high fluoride groups were lower (0.93 ± 0.05, 0.48 ± 0.02 vs 1.00 ± 0.02, P < 0.05). Conclusion:Fluoride exposure can induce autophagy in NG108-15 cells, and the expression of AMPK and ULK1 are up-regulated, while the expression of mTOR is down-regulated.

Expression of 5-methylcytosine and 5-hydroxymethylcytosine in bone tissue of rats with different types of skeletal fluorosis / 中华地方病学杂志

Objective:To learn about the levels of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in bone tissue of rats with different types of skeletal fluorosis and analyze their correlation.Methods:Thirty 4-week-old SPF grade healthy SD rats were selected. After adaptive feeding for 1 week, the rats were divided into control group (4 ml·kg -1·bw deionized water + standard maintenance diet), osteosclerosis group [20 mg·kg -1·bw sodium fluoride (NaF) + standard maintenance diet], and osteoporosis/osteomalacia group (20 mg·kg -1·bw NaF + low-calcium and low-protein partial diet) according to their body weight (100 - 120 g) by random number table method, with 10 rats in each group, half male and half female; gavaged 6 days each week and the experimental period was 5 months. At the end of the experiment, samples of rat heart blood and lower limb femur were collected. The contents of serum methyl donor S-adenosylmethionine (SAM) and its metabolite S-adenosylhomocysteine (SAH) in serum, and the levels of 5-mC and 5-hmC in bone tissue were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was used to determine the expression of DNA methyltransferase (DNMTs) and DNA hydroxymethylase (TETs) in bone tissue of rats. The correlation between serum SAM content, SAM/SAH ratio and bone tissue 5-mC level, and between the bone tissue 5-mC level and 5-hmC level was analyzed. Results:Serum SAM [11.03 (7.06, 18.63), 3.96 (2.32, 9.09), 3.91 (2.35, 4.46) nmol/L], SAH content [(4.69 ± 0.55), (5.41 ± 1.13), (13.90 ± 1.09) ng/L], SAM/SAH ratio [2.58 (1.54, 4.12), 0.62 (0.52, 1.69), 0.14 (0.13, 0.15)] and bone tissue 5-mC [103.39 (97.37, 109.35), 52.50 (50.19, 68.13), 55.03 (49.97, 59.57) ng/L], 5-hmC levels [(32.61 ± 8.84), (56.96 ± 8.48), (20.34 ± 6.22) ng/L] in the control group, osteosclerosis group and osteoporosis/osteomalacia group were compared, and the differences were statistically significant beween three groups ( H/ F = 12.81, 284.24, 21.85, 19.37, 55.23, P < 0.01). Compared with the control group, the content of SAM, the ratio of SAM/SAH, the level of 5-mC in the osteosclerosis group and osteoporosis/osteomalacia group, and the level of 5-hmC in the osteoporosis/osteomalacia group were lower ( P < 0.05), while the content of SAH in the osteoporosis/osteomalacia group and the level of 5-hmC in the osteosclerosis group were higher ( P < 0.05). Compared with the osteosclerosis group, the content of SAH in the osteoporosis/osteomalacia group was higher, while the ratio of SAM/SAH and the level of 5-hmC were lower ( P < 0.05). Western blot showed that there were statistically significant differences in the expression levels of DNMT1, DNMT3A, DNMT3B, TET1 and TET2 protein in bone tissue of rats in the control group, osteosclerosis group, and osteoporosis/osteomalacia group ( F = 285.45, 345.58, 239.83, 311.52, 318.24, P < 0.001). Among them, the expression levels of DNMT1, DNMT3A and DNMT3B protein in the osteosclerosis group and osteoporosis/osteomalacia group were lower than those in the control group, and the expression levels of DNMT1, DNMT3A and DNMT3B protein in the osteosclerosis/osteomalacia group were lower than those in the osteosclerosis group ( P < 0.05); the expression levels of TET1 and TET2 protein in osteosclerosis group were higher than those in the control group and osteoporosis/osteomalacia group, and the expression levels of TET1 and TET2 protein in the osteoporosis/osteomalacia group were lower than those in the control group ( P < 0.05). The results of Spearman rank correlation analysis showed that the content of SAM and the ratio of SAM/SAH in the control group, osteosclerosis group and osteoporosis/osteomalacia group were positively correlated with the level of 5-mC in bone tissue ( rs = 0.89, 0.92, 0.81, 0.73, 0.87, 0.73, P < 0.05). The levels of 5-mC and 5-hmC in bone tissue of rats in each group were negatively correlated ( rs = - 0.69, - 0.68, - 0.72, P < 0.05). Conclusions:The level of 5-mC in bone tissue of osteosclerotic fluorosis rats is low, and the level of 5-hmC is high, while those of osteoporosis/osteomalacia fluorosis rats are lower. The difference of 5-mC level in bone tissue of rats with different types of skeletal fluorosis is not significant, which may be related to the difference of 5-hmC level in bone tissue.

Analysis of external quality control assessment results of fluorine and arsenic in Qinghai Province in 2021 / 中华地方病学杂志

Objective:To learn about the detection quality and external quality control assessment of fluoride and arsenic in laboratories at all levels in Qinghai Province.Methods:The Z-score method was used to analyze and evaluate the evaluation results of 1 provincial, 8 municipal and 43 county level laboratories of disease prevention and control institutions participating in the external quality control assessment of water fluoride and brick tea fluoride in Qinghai Province in 2021, as well as 1 provincial, 1 municipal and 2 county level laboratories of disease prevention and control institutions participating in the external quality control assessment of water arsenic and urine arsenic. The feedback rate and qualification rate of external quality control of each assessment laboratory were calculated.Results:In 2021, the feedback rate of external quality control of water fluoride, brick tea fluoride, water arsenic and urine arsenic in provincial and municipal level laboratories of Qinghai Province were 100.00%; except that the qualified rate of water fluoride was 7/9, the qualified rate of external quality control of other projects was 100.00%. The feedback rate of external quality control of water fluoride, brick tea fluoride, water arsenic and urine arsenic in county level laboratories was 100.00%; except that the qualified rate of water fluoride was 86.05% (37/43), the qualified rate of external quality control of other projects was 100.00%. In the specific assessment results of the laboratory, the assessment results of water fluoride sample FS20210101 from 1 provincial, 1 municipal and 2 county level laboratories, and FS20210102 from 1 county level laboratory were suspicious; the assessment results of water fluoride sample FS20210101 from 3 county level laboratories were not satisfactory; the assessment results of fluoride and arsenic sample in other laboratories were satisfactory.Conclusions:The qualified rate of external quality control of fluoride and arsenic in laboratories at all levels in Qinghai Province is relatively high, but some county level laboratories are still dissatisfied with the assessment results of water fluoride. Therefore, it is necessary to strengthen the detection level of water fluoride in laboratories.

Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity, and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration (FDA). Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs' toxicities, but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common "click chemistry" labels. Taking the widely used non-steroidal anti-inflammatory drug acetaminophen (APAP) as an example, we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label. Cell toxicity studies indicated our analogue has similar activity to the parent drug. This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotin-SH probe for subsequent fluorine-thiol displacement reactions (FTDRs). This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting. Our preliminary validation results supported the interaction of APAP with the thioredoxin protein, which is an important redox protein for normal liver function. These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest, allowing for global profiling of interacting proteins. The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

Endemic dental fluorosis in children from a brazilian slave-descendent community: a cross-sectional study / Fluorose dentária endêmica em crianças de uma comunidade quilombola brasileira: um estudo transversal

Although fluoride (F) is required for the normal growth and development of several human organs and tissues, excessive exposure to it may be potentially toxic. Groundwater may present ranging levels of F; however, the appearance, taste, and smell are not altered. Thus, the present study aimed to evaluate dental fluorosis in children from a Brazilian slave-descendent community, as well as to assess F levels in the drinking water supplies available in that area. For that, 21 children aged from 6 to 14 years living in Rincão dos Martimianos were invited to participate. Thylstrup and Fejerskov index (a 0­9 scale) was used to assess dental fluorosis on permanent teeth. Furthermore, the F concentration of two water samples (from the artesian well and a tank) was determined by using a potentiometric method. All children presented dental fluorosis to some degree, ranging from score 2 to 9. About 81% of them had dental fluorosis scores equal to or over 5. Scores lower than 5 were observed only in children younger than 8 years; on the other hand, all children older than 8 years presented scores higher than 5. Moreover, artesian well water had an F concentration of 5 mg/L and tank water 0.8 mg/L. It is suggested that the F-rich groundwater supply was most probably responsible for dental fluorosis in that area. Brazilian slave-descendent communities, therefore, should receive constant attention from their local authorities in order to guarantee a proper water supply for consumption, as well as to provide public health education(AU)

Embora o flúor (F) seja necessário para o crescimento e desenvolvimento normal de vários órgãos e tecidos humanos, a exposição excessiva pode ser potencialmente tóxica. As águas subterrâneas podem apresentar níveis variados de F; no entanto, a aparência, o sabor e o cheiro não são alterados. Desta forma, o presente estudo teve como objetivo avaliar a fluorose dentária em crianças de uma comunidade brasileira descendente de escravos, bem como avaliar os níveis de F na água potável disponível nessa área. Para isso, 21 crianças de 6 a 14 anos residentes no Rincão dos Martimianos foram convidadas a participar da pesquisa. O índice de Thylstrup e Fejerskov (uma escala de 0 a 9) foi usado para avaliar a fluorose dentária em dentes permanentes. Além disso, a concentração de F de duas amostras de água (do poço artesiano e de um tanque) foi determinada pelo método potenciométrico. Todas as crianças apresentaram algum grau de fluorose dentária, variando de 2 a 9. Cerca de 81% delas apresentaram escores de fluorose dentária iguais ou superiores a 5. Escores inferiores a 5 foram observados apenas em crianças menores de 8 anos; por outro lado, todas as crianças maiores de 8 anos apresentaram escores superiores a 5. Além disso, a água do poço artesiano tinha concentração de F de 5 mg/L e a água do tanque 0,8 mg/L. Desta forma, acredita-se que a fonte de água subterrânea rica em F foi provavelmente responsável pela fluorose dentária na região avaliada. As comunidades quilombolas brasileiras, portanto, devem receber atenção constante de suas autoridades locais, a fim de garantir o abastecimento adequado de água para consumo, bem como proporcionar educação em saúde pública(AU)

Análise do teor de fluoretos nas águas de abastecimento público em um município da região metropolitana de Curitiba/PR: doze meses de heterocontrole / Analysis of fluoride content in the public water supply in a city of the metropolitan region of Curitiba/PR: twelve months of external control

Resumo Introdução A fluoretação das águas de abastecimento tem sido apontada em estudos nacionais e internacionais como a mais eficiente e equânime forma de acesso a fluoretos na prevenção da cárie dentária. Objetivo Relatar os resultados do heterocontrole nas águas de abastecimento público do município de Colombo/PR, no período de dezembro de 2013 a novembro de 2014. Método Foram coletadas amostras mensais em 15 Unidades Básicas de Saúde, em dias da semana aleatórios, no período de 12/2013 a 11/2014. As amostras foram analisadas pelo método eletrométrico na Faculdade de Odontologia da Universidade Federal Fluminense. Resultados Foram analisadas 180 amostras, que variaram de <0,001 a 1,480 mg/L (média 0,715±0,232 mg/L). De acordo com o critério estabelecido pelo Centro Colaborador do Ministério da Saúde em Vigilância da Saúde Bucal, 51,11% das amostras apresentavam níveis de fluoretos adequados, 13,34% concentrações de flúor acima do ideal, e 35,56% abaixo do ideal. Conclusão O heterocontrole representa uma das principais estratégias de vigilância em saúde bucal, e, dessa forma, deve ser implementado e efetuado em todas as regiões que utilizam água fluoretada, a fim de garantir a manutenção de níveis ótimos de fluoretos.

Abstract Background The fluoridation of water supply has been pointed out in national and international studies as the most efficient and equal way of accessing fluorides in the prevention of dental caries. Objective To report the results of heterocontrol in public water supply in the municipality of Colombo/PR, from December 2013 to November 2014. Method The samples were monthly collected in 15 Basic Health Units, on random days of the week, from 12/2013 to 11/2014. The samples were analyzed by the electrometric method at the Faculty of Dentistry of Fluminense Federal University. Results 180 samples were analyzed, ranging from <0.001 to 1.480 mg/L (mean 0.715 ± 0.232 mg/L). According to the criteria established by the Collaborating Center of the Ministry of Health in Oral Health Surveillance, 51.11% of the samples had adequate fluoride levels, 13.34% above ideal fluoride levels, and 35.56% below ideal levels. Conclusion Heterocontrol could represent one of the main strategies of oral health surveillance, and, therefore, it should be implemented and carried out in all regions that use fluoridated water, in order to guarantee the maintenance of optimal fluoride levels.

Geographical barriers to the use of toothpaste containing ≥1000 ppm fluoride in peruvian children / Barreras geográficas para el uso de pasta dental con fluoruro ≥1000 ppm en niños peruanos

Objective: The aim of this was to determine the geographical barriers for the use of equal or more than 1000 (≥1000) parts per million (ppm) of toothpaste with fluorine (F) in children aged 1 to 11 years in Peru in 2018. Material and Methods: This is a cross-sectional study, the database of Demographic and Family Health Survey (ENDES, for its Spanish acronym) of Peru in 2018 was used; the final sample was 25660 records of children between 1 and 11 years old. The variables evaluated were the use of ≥1000 ppm fluoride toothpaste, place of residence, natural region, area of residence, region, wealth index, access to dental service, whether information was received about oral hygiene, daily tooth brushing, age and sex. A descriptive, bivariate (Chi square) and multivariate (log-linear Poisson regression) analysis was performed. Results: An association was found between the use of toothpaste ≥1000 ppm F with place of residence: small city vs capital-large city with an adjusted prevalence ratio (RPa): 0.94; 95% confidence interval (95% IC): 0.90-0.98, town and country vs. capital-large city both with an RPa: 0.95; 95% CI: 0.91-0.99. With natural region: rest of the Coast vs Lima with RPa: 0.94; 95% CI: 0.91-0.98, Sierra vs Lima with RPa: 0.95; 95% CI: 0.92-0.99 and Jungle vs Lima with RPa: 0.94; 95% CI: 0.90-0.98). Conclusion: The place of residence and the natural region are geographic barriers to the use ≥1000 ppm fluoride toothpaste in children aged between 1 and 11 years in Peru in 2018.

Objetivo: El objetivo de este fue determinar las barreras geográficas para el uso de igual o más de 1000 (≥1000) partes por millón (ppm) de pasta dental con flúor (F) en niños de 1 a 11 años en Perú en 2018. Material y Métodos: Se trata de un estudio transversal, la base de datos de la Encuesta Demográfica y de Salud Familiar (ENDES) del Perú en 2018 fue usada con una muestra de 25 660 registros de niños entre 1 y 11 años. Las variables evaluadas fueron el uso de pasta dental ≥1000 ppm F, lugar de residencia, región natural, área de residencia, región, índice de riqueza, acceso al servicio odontológico, si se recibió información sobre higiene bucal, cepillado diario de dientes, edad y sexo. Se realizó un análisis descriptivo, bivariado (Chi cuadrado) y multivariado (regresión loglineal de Poisson). Resultados: Se encontró una asociación entre el uso de pasta dental ≥1000 ppm F con el lugar de residencia: ciudad pequeña vs ciudad capital-grande con una razón de prevalencia ajustada (RPa): 0,94; intervalo de confianza de 95% (IC 95%): 0,90-0,98, ciudad y campo vs. capital-grande ciudad ambos con un RPa: 0,95; IC 95%: 0,91-0,99. Con región natural: resto de la Costa vs Lima con RPa: 0,94; IC 95%: 0,91-0,98, Sierra vs Lima con RPa: 0,95; IC 95%: 0,92-0,99 y Selva vs Lima con RPa: 0,94; 95% % CI: 0,90-0,98. Conclusión: El lugar de residencia y la región natural son barreras geográficas para el uso de pasta dental fluorada ≥1000 ppm en niños de 1 a 11 años en Perú en 2018.

Evaluation of external quality control assessment results of fluoride in brick tea in Qinghai Provincial endemic fluorosis laboratories from 2014 to 2020 / 中华地方病学杂志

Objective:To analyze the external quality control assessment results of fluoride in brick tea in the provincial, city (prefecture) and county (city, district)-level endemic fluorosis laboratories in Qinghai Province, and to evaluate the testing capabilities of laboratories at all levels.Methods:The Z-score method was used to analyze and evaluate the results of provincial, city (prefecture) and county (city, district)-level laboratories that participated in the external quality control assessment of fluoride in brick tea in Qinghai Province from 2014 to 2020, and│Z│≤2 was qualified; 2 <│Z│ < 3 was basic qualified; │Z│≥3 was unqualified.Results:From the feedback, the feedback rate of external quality control of fluoride in brick tea in provincial and city (prefecture)-level laboratories in Qinghai Province from 2014 to 2020 was 100.00%; the feedback rate of county (city, district)-level laboratories from 2014 to 2018 was 100.00%, and there were no feedback units in 2019 and 2020. From the assessment of qualification, the qualification rate of provincial, city (prefecture)-level laboratories was 100.00% in all other years except one unit failed in 2017; the qualification rate of county (city, district)-level laboratories was 100.00% in 2014, 2015, 2016 and 2019, and there were 6 unqualified units in other years.Conclusions:From 2014 to 2020, some endemic fluorosis laboratories in Qinghai Province still fail to pass the external quality control assessment of fluoride in brick tea. In the future, it will be the focus of work to strengthen personnel training and improve the detection ability.

Research progress on the effects of fluoride on intestinal structure and defense function / 中华地方病学杂志

Fluorine is a non-metallic chemical element, which often exists in the form of fluoride in nature. Long-term excessive intake of fluoride will lead to chronic fluorosis. Fluoride is mainly absorbed through the digestive tract, so the intestinal tract is more vulnerable to fluoride damage. Excessive fluoride not only destroys intestinal structure and interferes with intestinal flora and micro-environment, but also induces intestinal toxicity through oxidative stress. This article reviews the effects of fluoride on intestinal structure and defense function, aiming to provide theoretical references and new ideas for the mechanism study of fluoride-induced intestinal damage.