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1.
Principles of fluoride toxicity and the cellular response: a review.
Johnston, NR, Strobel, SA
Archives of toxicology. 2020;(4):1051-1069
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Abstract
Fluoride is ubiquitously present throughout the world. It is released from minerals, magmatic gas, and industrial processing, and travels in the atmosphere and water. Exposure to low concentrations of fluoride increases overall oral health. Consequently, many countries add fluoride to their public water supply at 0.7-1.5 ppm. Exposure to high concentrations of fluoride, such as in a laboratory setting often exceeding 100 ppm, results in a wide array of toxicity phenotypes. This includes oxidative stress, organelle damage, and apoptosis in single cells, and skeletal and soft tissue damage in multicellular organisms. The mechanism of fluoride toxicity can be broadly attributed to four mechanisms: inhibition of proteins, organelle disruption, altered pH, and electrolyte imbalance. Recently, there has been renewed concern in the public sector as to whether fluoride is safe at the current exposure levels. In this review, we will focus on the impact of fluoride at the chemical, cellular, and multisystem level, as well as how organisms defend against fluoride. We also address public concerns about fluoride toxicity, including whether fluoride has a significant effect on neurodegeneration, diabetes, and the endocrine system.
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Scenario, perspectives and mechanism of arsenic and fluoride Co-occurrence in the groundwater: A review.
Kumar, M, Goswami, R, Patel, AK, Srivastava, M, Das, N
Chemosphere. 2020;:126126
Abstract
Arsenic (As) and fluoride (F-) are the two most conspicuous contaminants, in terms of distribution and menace, in aquifers around the world. While the majority of studies focus on the individual accounts of their hydro-geochemistry, the current work is an effort to bring together the past and contemporary works on As and F- co-occurrence. Co-occurrence in the context of As and F- is a broad umbrella term and necessarily does not imply a positive correlation between the two contaminants. In arid oxidized aquifers, healthy relationships between As and F- is reported owing desorption based release from the positively charged (hydr)oxides of metals like iron (Fe) under alkaline pH. In many instances, multiple pathways of release led to little or no correlation between the two, yet there were high concentrations of both at the same time. The key influencer of the strength of the co-occurrence is seasonality, environment, and climatic conditions. Besides, the existing primary ion and dissolved organic matter also affect the release and enrichment of As-F- in the aquifer system. Anthropogenic forcing in the form of mining, irrigation return flow, extraction, recharge, and agrochemicals remains the most significant contributing factor in the co-occurrence. The epidemiological indicate that the interface of these two interacting elements concerning public health is considerably complicated and can be affected by some uncertain factors. The existing explanations of interactions between As-F are indecisive, especially their antagonistic interactions that need further investigation. "Multi-contamination perspectives of groundwater" is an essential consideration for the overarching question of freshwater sustainability.
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A randomised oral fluoride retention study comparing intra-oral kinetics of fluoride-containing dentifrices before and after dietary acid exposure.
Burnett, G, Nehme, M, Parkinson, C, Karwal, R, Badrock, T, Thomas, GV, Hall, P
Archives of oral biology. 2020;:104891
Abstract
OBJECTIVE This exploratory, randomised, single-blind, crossover, study evaluated fluoride and calcium ion concentrations and pH following use of one of two 1450 ppm fluoride (NaF), 5% w/w KNO3 dentifrices: (1) test dentifrice (with cocamidopropyl betaine) with an orange juice (OJ) rinse; (2) test dentifrice with a deionized (DI) water rinse or (3) comparator dentifrice (with sodium lauryl sulphate and tetrasodium pyrophosphate) with an OJ rinse. DESIGN Eighteen participants used their assigned dentifrice, rinsed with DI water, then expectorate was collected. Sixty min post-brushing, participants rinsed with OJ or DI water then expectorate was collected. Saliva samples were collected pre-brushing and at 1, 5, 10, 15, 30 and 60 min post-brushing and following the 60 min OJ/DI water rinse. The pH of samples was taken. RESULTS Significant differences (p < 0.05) were found in salivary fluoride ion concentrations between test and comparator dentifrices at 30 and 60 min and following the 60 min OJ rinse, favouring the former. Significant differences were also found between test and comparator dentifrices for salivary calcium ion concentration at 1, 5 and 10 min (p < 0.0001), favouring the former, and between test or comparator + OJ rinse and test + water rinse (p < 0.005), favouring the latter. No pH differences were shown prior to OJ/water rinse. Products were generally well-tolerated. CONCLUSIONS Results confirmed that acid-labile fluoride is released from the oral cavity following a dietary acid challenge and showed that formulation excipients may impact on retention of such.
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Oral biofilm uptake of mineral ions released from experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) filler.
Kato, K, Tamura, K, Shimazaki, Y
Archives of oral biology. 2020;:104777
Abstract
OBJECTIVE To clarify the fluoride/mineral kinetics in an oral biofilm following concurrent application of fluoride and other mineral ions released from experimental toothpaste containing S-PRG filler using depth-specific analysis. STUDY DESIGN Twenty subjects wore in situ plaque-generating devices, comprised of a pair of enamel slabs, and a biofilm was allowed to form. The devices were removed after three days, immersed in the toothpaste filtrate containing Al, B, Sr and F ions for 1 min, and then reinserted at the same location. After 30 min, the devices were removed and samples were obtained by sectioning into outer, middle and inner biofilm layers (300-μm thick). Samples treated with filtrate containing F without S-PRG filler extract served as the control. Fluoride and the three other mineral ions extracted from 4-μm sections were quantified using a fluoride electrode and ICP-AES, respectively. The results were corrected for biomass volume, estimated by the area measurement of stained 2-μm sections. RESULTS The mean uptake ratios (S-PRG/control, ng/mm3) of Al, B, Sr and F were 186.6/53.7, 58.4/25.0, 456.9/125.7 and 43.6/12.0, respectively, in the outer layer, indicating that the mineral ions could easily diffuse into the biofilm. F concentrations in the outer biofilm treated using filtrate with S-PRG filler extract were significantly higher than those in controls, although both biofilms were exposed to filtrates containing the same level of F. CONCLUSIONS The results suggest that toothpaste containing S-PRG filler promotes fluoride retention in oral biofilms via the uptake of other mineral ions.
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Use of Fluoride as a Marker Solute to Quantify the Current Effective Delivered Dose in Continuous Renal Replacement Therapy: An "in vitro" Study.
Villa, G, Bocciero, V, Neri, M, Pomarè Montin, D, Angeli, E, Di Filippo, A, Falsini, S, Adembri, C, De Gaudio, AR, Romagnoli, S
Blood purification. 2020;(6):685-691
Abstract
BACKGROUND The current effective delivered dose is a quality indicator for continuous renal replacement therapy. Its periodic assessment might enable physicians to deliver personalised treatments. Yet, its quantification as by extracorporeal urea clearance (Cl) is cumbersome and thus often neglected in routine practice. The aim of this in vitro study is to demonstrate the non-inferior effectiveness of assessing the current effective delivered dose using a simpler, cheaper and faster approach based on measurement of fluoride rather than urea extracorporeal Cl. METHODS We compared urea and fluoride removal in 3 post-dilution continuous veno-venous haemofiltration (CVVH) and 3 continuous veno-venous haemodialysis (CVVHD) in vitro experimental models. Experiments ran for 180 min, using 3 L of human blood, heparin anticoagulation and a machine dose of 30 mL/kg/h. Urea and fluoride were measured in the inflow, outflow and effluent lines to compare sieving coefficients (SC), saturation coefficients (SA) and transmembrane Cls. RESULTS In CVVH, the median SC values were 1.06 (1.02-1.07) and 1.02 (1.01-1.04) for fluoride and urea, respectively (discrepancy of 4.3%), while transmembrane convective Cls were 31.28 (30.01-31.31) mL/kg/h and 30.30 (29-31.85) mL/kg/h (discrepancy of 3.13%), respectively. In CVVHD, the median SA values were 1.01 (0.96-1.02) and 1 (0.95-1.01) for fluoride and urea, respectively (discrepancy of 1.6%), while transmembrane dialytic Cls were 30.26 (29.52-31.32) mL/kg/h and 31.16 (30-31.75) mL/kg/h (discrepancy of -2.97%), respectively. CONCLUSION Fluoride transmembrane removal was close to that observed with urea, in terms of SC, SA and transmembrane Cl. Fluoride seems as much accurate as urea in assessing the current effective delivered dose during both CVVH and CVVHD and might therefore be adopted for dose measurement. Besides accuracy, fluoride bedside assessment could present many advantages over urea, particularly in terms of availability, costs, time requirement and rapidity of assessment.
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Influence of Hydroxyapatite Coating for the Prevention of Bone Mineral Density Loss and Bone Metabolism after Total Hip Arthroplasty: Assessment Using 18F-Fluoride Positron Emission Tomography and Dual-Energy X-Ray Absorptiometry by Randomized Controlled Trial.
Tezuka, T, Kobayashi, N, Hyonmin, C, Oba, M, Miyamae, Y, Morita, A, Inaba, Y
BioMed research international. 2020;:4154290
Abstract
BACKGROUND Hydroxyapatite- (HA-) coated implants tend to achieve good osteoinductivity and stable clinical results; however, the influence of the coating on the prevention of bone mineral density (BMD) loss around the implant is unclear. The purpose of this randomized controlled trial was to evaluate the effectiveness of HA-coated implants for preventing BMD loss and to determine the status of bone remodeling after total hip arthroplasty (THA), making comparisons with non-HA-coated implants. METHODS A total of 52 patients who underwent primary THA were randomly allocated to HA and non-HA groups. BMD was measured by dual-energy X-ray absorptiometry (DEXA) at 1 week postoperation to form a baseline measurement, and then 24 weeks and 48 weeks after surgery. The relative change in BMD was evaluated for regions of interest (ROIs) based on the Gruen zone classifications. 18F-fluoride positron emission tomography (PET) was performed at 24 weeks postsurgery, and the maximum standardized uptake values (SUVmax) were evaluated in the proximal (HA-coated) and distal (non-HA-coated) areas in both groups. RESULTS There were significant differences in BMD loss in ROIs 3 and 6 (p = 0.03), while no significant difference was observed in ROI 7 at either 24 or 48 weeks postsurgery. There was no significant correlation between PET uptake and BMD (24 or 48 weeks) in either group. CONCLUSION The influence of a HA coating in terms of BMD preservation is limited. No significant correlation was found between BMD and SUVmax measured by PET, either with or without the use of a HA coating.
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Zinc-Calcium-Fluoride Bioglass-Based Innovative Multifunctional Dental Adhesive with Thick Adhesive Resin Film Thickness.
Yao, C, Ahmed, MH, Li, X, Nedeljkovic, I, Vandooren, J, Mercelis, B, Zhang, F, Van Landuyt, KL, Huang, C, Van Meerbeek, B
ACS applied materials & interfaces. 2020;(27):30120-30135
Abstract
Apart from producing high bond strength to tooth enamel and dentin, a dental adhesive with biotherapeutic potential is clinically desirable, aiming to further improve tooth restoration longevity. In this laboratory study, an experimental two-step universal adhesive, referred to as Exp_2UA, applicable in both the etch-and-rinse (E&R) and self-etch (SE) modes and combining a primer, containing 10-methacryloyloxydecyldihydrogen phosphate as a functional monomer with chemical binding potential to hydroxyapatite, with a bioglass-containing hydrophobic adhesive resin, was multifactorially investigated. In addition to primary property assessment, including measurement of bond strength, water sorption, solubility, and polymerization efficiency, the resultant adhesive-dentin interface was characterized by transmission electron microscopy (TEM), the filler composition was analyzed by energy-dispersive X-ray spectroscopy, and the bioactive potential of the adhesive was estimated by measuring the long-term ion release and assessing its antienzymatic and antibacterial potential. Four representative commercial adhesives were used as reference/controls. Application in both the E&R and SE modes resulted in a durable bonding performance to dentin, as evidenced by favorable 1 year aged bond strength data and a tight interfacial ultrastructure that, as examined by TEM, remained ultramorphologically unaltered upon 1 year of water storage aging. TEM revealed a 20 μm thick hydrophobic adhesive layer with a homogeneous bioglass filler distribution. Adequate polymerization conversion resulted in extremely low water sorption and solubility. In situ zymography revealed reduced endogenous proteolytic activity, while Streptococcus mutans biofilm formation was inhibited. In conclusion, the three-/two-step E&R/SE Exp_2UA combines the high bonding potential and bond degradation resistance with long-term ion release, rendering the adhesive antienzymatic and antibacterial potential.
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Developmental fluoride neurotoxicity: an updated review.
Grandjean, P
Environmental health : a global access science source. 2019;(1):110
Abstract
BACKGROUND After the discovery of fluoride as a caries-preventing agent in the mid-twentieth century, fluoridation of community water has become a widespread intervention, sometimes hailed as a mainstay of modern public health. However, this practice results in elevated fluoride intake and has become controversial for two reasons. First, topical fluoride application in the oral cavity appears to be a more direct and appropriate means of preventing caries. Second, systemic fluoride uptake is suspected of causing adverse effects, in particular neurotoxicity during early development. The latter is supported by experimental neurotoxicity findings and toxicokinetic evidence of fluoride passing into the brain. METHOD An integrated literature review was conducted on fluoride exposure and intellectual disability, with a main focus on studies on children published subsequent to a meta-analysis from 2012. RESULTS Fourteen recent cross-sectional studies from endemic areas with naturally high fluoride concentrations in groundwater supported the previous findings of cognitive deficits in children with elevated fluoride exposures. Three recent prospective studies from Mexico and Canada with individual exposure data showed that early-life exposures were negatively associated with children's performance on cognitive tests. Neurotoxicity appeared to be dose-dependent, and tentative benchmark dose calculations suggest that safe exposures are likely to be below currently accepted or recommended fluoride concentrations in drinking water. CONCLUSION The recent epidemiological results support the notion that elevated fluoride intake during early development can result in IQ deficits that may be considerable. Recognition of neurotoxic risks is necessary when determining the safety of fluoride-contaminated drinking water and fluoride uses for preventive dentistry purposes.
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Does Measurement of First-Order and Heterogeneity Parameters Improve Response Assessment of Bone Metastases in Breast Cancer Compared to SUVmax in [18F]fluoride and [18F]FDG PET?
Azad, GK, Cousin, F, Siddique, M, Taylor, B, Goh, V, Cook, GJR
Molecular imaging and biology. 2019;(4):781-789
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Abstract
PURPOSE To establish whether first-order statistical features from [18F]fluoride and 2-deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) demonstrate incremental value in skeletal metastasis response assessment compared with maximum standardised uptake value (SUVmax). PROCEDURES Sixteen patients starting endocrine treatment for de novo or progressive breast cancer bone metastases were prospectively recruited to undergo [18F]fluoride and [18F]FDG PET/CT scans before and 8 weeks after treatment. Percentage changes in SUV parameters, metabolic tumour volume (MTV), total lesion metabolism (TLM), standard deviation (SD), entropy, uniformity and absolute changes in kurtosis and skewness, from the same ≤ 5 index lesions, were measured. Clinical response to 24 weeks, assessed by two experienced oncologists blinded to PET/CT imaging findings, was used as a reference standard and associations were made between parameters and progression free and overall survival. RESULTS [18F]fluoride PET/CT: In four patients (20 lesions) with progressive disease (PD), TLM and kurtosis predicted PD better than SUVmax on a patient basis (4, 4 and 3 out of 4, respectively) and TLM, entropy, uniformity and skewness on a lesion basis (18, 16, 16, 18 and 15 out of 20, respectively). Kurtosis was independently associated with PFS (p = 0.033) and OS (p = 0.008) on Kaplan-Meier analysis. [18F]FDG PET No parameter provided incremental value over SUVmax in predicting PD or non-PD. TLM was significantly associated with OS (p = 0.041) and skewness with PFS (p = 0.005). Interlesional heterogeneity of response was seen in 11/16 and 8/16 patients on [18F]fluoride and [18F]FDG PET/CT, respectively. CONCLUSION With [18F]fluoride PET/CT, some first-order features, including those that take into account lesion volume but also some heterogeneity parameters, provide incremental value over SUVmax in predicting clinical response and survival in breast cancer patients with bone metastases treated with endocrine therapy. With [18F]FDG PET/CT, no first-order parameters were more accurate than SUVmax although TLM and skewness were associated with OS and PFS, respectively. Intra-patient heterogeneity of response occurs commonly between metastases with both tracers and most parameters.
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Metabolic Profile of Supragingival Plaque Exposed to Arginine and Fluoride.
Nascimento, MM, Alvarez, AJ, Huang, X, Browngardt, C, Jenkins, R, Sinhoreti, MC, Ribeiro, APD, Dilbone, DA, Richards, VP, Garrett, TJ, et al
Journal of dental research. 2019;(11):1245-1252
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Abstract
Caries lesions develop when acid production from bacterial metabolism of dietary carbohydrates outweighs the various mechanisms that promote pH homeostasis, including bacterial alkali production. Therapies that provide arginine as a substrate for alkali production in supragingival oral biofilms have strong anticaries potential. The objective of this study was to investigate the metabolic profile of site-specific supragingival plaque in response to the use of arginine (Arg: 1.5% arginine, fluoride-free) or fluoride (F: 1,100 ppm F/NaF) toothpastes. Eighty-three adults of different caries status were recruited and assigned to treatment with Arg or F for 12 wk. Caries lesions were diagnosed using International Caries Detection and Assessment System II, and plaque samples were collected from caries-free and carious tooth surfaces. Taxonomic profiles were obtained by HOMINGS (Human Oral Microbe Identification using Next Generation Sequencing), and plaque metabolism was assessed by the levels of arginine catabolism via the arginine deiminase pathway (ADS), acidogenicity, and global metabolomics. Principal component analysis (PCA), partial least squares-discriminant analysis, analysis of variance, and random forest tests were used to distinguish metabolic profiles. Of the 509 active lesions diagnosed at baseline, 70 (14%) were inactive after 12 wk. Generalized linear model showed that enamel lesions were significantly more likely to become inactive compared to dentin lesions (P < 0.0001), but no difference was found when treatment with Arg was compared to F (P = 0.46). Arg significantly increased plaque ADS activity (P = 0.031) and plaque pH values after incubation with glucose (P = 0.001). F reduced plaque lactate production from endogenous sources (P = 0.02). PCA revealed differences between the metabolic profiles of plaque treated with Arg or F. Arg significantly affected the concentrations of 16 metabolites, including phenethylamine, agmatine, and glucosamine-6-phosphate (P < 0.05), while F affected the concentrations of 9 metabolites, including phenethylamine, N-methyl-glutamate, and agmatine (P < 0.05). The anticaries mechanisms of action of arginine and fluoride are distinct. Arginine metabolism promotes biofilm pH homeostasis, whereas fluoride is thought to enhance resistance of tooth minerals to low pH and reduce acid production by supragingival oral biofilms.