A cost-effectiveness analysis of fluoride varnish application in preventing Root caries in elderly persons: a Markov simulation study.

BACKGROUND: Root caries are prevalent issues that affect dental health, particularly among elderly individuals with exposed root surfaces. Fluoride therapy has shown effectiveness in preventing root caries, but limited studies have addressed its cost-effectiveness in elderly persons population. This study aimed to evaluate the cost-effectiveness of a fluoride treatment program for preventing root caries in elderly persons within the context of Chinese public healthcare. METHODS: A Markov simulation model was adopted for the cost-effectiveness analysis in a hypothetical scenario from a healthcare system perspective. A 60-year-old subject with 23 teeth was simulated for 20 years. A 5% sodium fluoride varnish treatment was compared with no preventive intervention in terms of effectiveness and cost. Tooth years free of root caries were set as the effect. Transition probabilities were estimated from the data of a community-based cohort and published studies, and costs were based on documents published by the government. The incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. Univariate and probabilistic sensitivity analyses were performed to evaluate the influence of data uncertainty. RESULTS: Fluoride treatment was more effective (with a difference of 10.20 root caries-free tooth years) but also more costly (with a difference of ¥1636.22). The ICER was ¥160.35 per root caries-free tooth year gained. One-way sensitivity analysis showed that the risk ratio of root caries in the fluoride treatment group influenced the result most. In the probabilistic sensitivity analysis, fluoride treatment was cost-effective in 70.5% of the simulated cases. CONCLUSIONS: Regular 5% sodium fluoride varnish application was cost-effective for preventing root caries in the elderly persons in most scenarios with the consideration of data uncertainty, but to a limited extent. Improved public dental health awareness may reduce the incremental cost and make the intervention more cost-effective. Overall, the study shed light on the economic viability and impact of such preventive interventions, providing a scientific basis for dental care policies and healthcare resource allocation.

Biphasic Functions of Sodium Fluoride (NaF) in Soft and in Hard Periodontal Tissues.

Sodium fluoride (NaF) is widely used in clinical dentistry. However, the administration of high or low concentrations of NaF has various functions in different tissues. Understanding the mechanisms of the different effects of NaF will help to optimize its use in clinical applications. Studies of NaF and epithelial cells, osteoblasts, osteoclasts, and periodontal cells have suggested the significant roles of fluoride treatment. In this review, we summarize recent studies on the biphasic functions of NaF that are related to both soft and hard periodontal tissues, multiple diseases, and clinical dentistry.

A Phase 1 Trial to Evaluate the Relationship Between Fluoride Intake and Urinary Fluoride Excretion in Healthy Participants.

Chronic overexposure to fluoride can have deleterious effects in the musculoskeletal system. Some fluorine-containing therapeutics, such as voriconazole, release fluoride through metabolism. Therefore, drug-related fluoride exposure should be assessed for novel therapeutics suspected of releasing fluoride through metabolism. Two trials were conducted to identify the optimal method of assessing drug-related fluoride exposure. In trial 1, designed to assess reproducibility of fluoride pharmacokinetics in urine and plasma, 14 participants were administered a fluoride-restricted diet and once-daily doses of sodium fluoride (2.2 mg [1 mg of fluoride] on days 1 and 2; and 13.2 mg of sodium fluoride [6 mg of fluoride] on days 3 and 4). In trial 2, designed to confirm the selected method for fluoride detection, 12 participants were administered a fluoride-restricted diet and randomized to receive voriconazole (400 mg twice, 12 hours apart, on day 1 [131 mg/d of fluoride maximum], then 3 doses of 200 mg every 12 hours [65.3 mg/d of fluoride maximum]) or placebo. Plasma fluoride concentrations and urinary fluoride excretion were assessed in each trial. Assessment of plasma fluoride concentrations in trial 1 was limited by 301 of 854 samples (35.2%) below the lower limit of quantitation. Urine fluoride excretion was readily measured and demonstrated a decrease from baseline during the fluoride-restricted diet phase, as well as dose-proportional increases with fluoride administration. In trial 2, increases in urine fluoride were successfully observed in participants administered voriconazole. In conclusion, fluoride exposure was optimally assessed by urinary fluoride excretion in conjunction with strict dietary fluoride restrictions, as measurements were consistent and reproducible.

Estimation of patient effective doses in PET/CT- 18F-Sodium Fluoride examinations.

The positron emitters (18F-Sodium Fluoride (NaF)) and X-rays used in Positron emission tomography (PET) combined with computed tomography (PET/CT) imaging have a high radiation dose, which results in a high patient dose. The present research intends to determine the radiation dose and risks associated with PET/CT- 18F-Sodium fluoride examinations in patients. The 18F-NaF PET/CT was used to investigate the doses of 86 patients. Patient exposure parameters and ImPACT software were used to calculate mean effective doses. The administered activity of 185 MBq (5.0 mCi) per procedure has a mean and range based on the patient's BMI (BMI). The range of patient effective doses per procedure was found to be 4-10 mSv, with a radiation risk of 1 × 10-5 per procedure. Patient doses are determined by the patient's size, scanner type, imaging protocol, and reconstruction method. For further dose reduction, proper justification and radiation dose optimization is required.

Effects of brief sodium fluoride treatments on the growth of early and mature cariogenic biofilms.

Although fluoride has been widely used as a preventive agent for dental caries, the effects of fluoride on the activities of biofilms in different stages of cariogenic biofilm formation are less studied. This study was designed to investigate the antibiofilm activity of sodium fluoride during the early and mature stages of Streptococcus mutans (S. mutans) biofilm formation. S. mutans biofilms were formed on saliva-coated hydroxyapatite disks. In the early (0-46 h) and mature (46-94 h) biofilm stages, the biofilms were treated with different concentrations of fluoride (250, 500, 1000, 2000 ppm; 5 times in total, 1 min/treatment). Acidogenicity, dry weight, colony-forming units (CFUs), water-soluble/insoluble extracellular polysaccharides (EPSs), and intracellular polysaccharides were analysed, and confocal laser scanning microscopy images were obtained of the two stages of biofilms to determine antibiofilm activities of fluoride at varying concentrations during the formation of early and mature biofilms. In the early stages of cariogenic biofilm formation, test groups with all fluoride concentrations significantly inhibited the growth of S. mutans biofilms. The antibiofilm and anti-EPS formation activities of the brief fluoride treatments increased with a concentration-dependent pattern. At the mature biofilm stage, only the 2000 ppm fluoride treatment group significantly inhibited biofilm accumulation, activity, and intracellular/extracellular polysaccharide content compared with those of the control and other fluoride treatment groups. The antimicrobial effect of fluoride treatment on the growth of S. mutans biofilms was linked with the stage of cariogenic biofilm formation. The inhibition of S. mutans biofilm growth by fluoride treatment was easier in the early formation stage than in the mature stage. Fluoride treatment in the early stage of cariogenic biofilm formation may be an effective approach to controlling cariogenic biofilm development and preventing dental caries.

The potential risks of chronic fluoride exposure on nephrotoxic via altering glucolipid metabolism and activating autophagy and apoptosis in ducks.

Fluoride is one of the most widely distributed elements in nature, while some fluorine-containing compounds are toxic to several vertebrates at certain levels. The current study was performed to evaluate the nephrotoxic effects of fluoride exposure in ducks. The results showed that the renal index was decreased in NaF group, and fluoride exposure significantly decreased the levels of serum Albumin, Glucose, Total cholesterol, Urea, protein and Triglycerides, confirming that NaF exhibited adverse effects on the kidney. The overall structure of renal cells showed damage with the signs of nuclelytic, vacuolar degeneration, atrophy, renal cystic cavity widening after fluoride induction. Renal vascular growth was impaired as the expression of VEGF and HIF-1α decreased (p > 0.05). More importantly, autophagy and apoptosis levels of CYT C, LC3, p62, Beclin, M-TOR, Bax and Caspase-3 were increased (p < 0.05) in the NaF treated group. Interestingly, our results showed that Phosphatidylethanolamine (PE) and Phosphatidylcholine (PC) activated the M-TOR autophagy pathway. Meanwhile, the PE acted on Atg5/ LC3 autophagy factor, followed by the auto-phagosome generation and activation of cell autophagy. These results indicate that NaF exposure to duck induced nephron-toxicity by activating autophagy, apoptosis and glucolipid metabolism pathways, which suggest that fluorine exposure poses a risk of poisoning.

Efficacy of bisphosphonates in detection of early enamel caries using NIR fluorescence imaging and inhibition of caries progression.

NIR fluorescence imaging using bisphosphonate-Indocyanine green has been indicated for early interproximal caries detection. This study assessed diagnostic accuracy of caries detection by NIR fluorescence imaging with OsteoSense 750® (OS750) in vitro and ex vivo, and to analyze the therapeutic efficacy of a bisphosphonate (Etidronate) in inhibiting enamel caries progression in vitro. Methods: Four experiments were conducted using extracted human teeth; 1) to calculate the infiltration rate of OS750 into interproximal white spot lesions using fluorescence microscope, 2) to assess diagnostic accuracy of interproximal natural white spot lesions using desktop NIR fluorescence imaging device in vitro setting, 3) to assess diagnostic accuracy of artificially created deeper enamel carious lesion (0.5 mm~1.0 mm) using NIR fluorescence image through the head-mount display in ex vivo setting, 4) to compare the progression on the enamel caries lesions treated by Etidronate, NaF and distilled-water. Diagnostic accuracy was analyzed using sensitivity, specificity and receiver operating curves (ROC). The caries progression was calculated with micro-CT and was statistically analyzed using a two-way ANOVA and the Tukey HDS post-hoc test. Results: 1) The infiltration rate of OS750 was 101.83% ± 8.66 (Min: 90.10%, Max: 133.94%). 2) The average of sensitivity and specificity in vitro setting experiments were 86.7% ± 4.4% and 70% ± 11%, respectively. The average of area under the ROC curves (AUC) was 0.883 ± 0.059 indicating excellent performance. 3) The mean sensitivity and specificity in ex vivo setting was 82.97% ± 15% and 76.78% ± 13.27% respectively. 4) The carious lesion volume treated by Etidronate was significantly smaller at post treatment-1 (p<0.05) and treatment-2 (p<0.01) than the control. There was no significant difference in lesion volume in the Etidronate and NaF group at the time point of post treatment-1. Conclusion: This study suggests that bisphosphonates contribute to both early diagnosis of enamel caries and inhibition of caries progression.

[18F]-sodium fluoride autoradiography imaging of nephrocalcinosis in donor kidneys and explanted kidney allografts.

Nephrocalcinosis is present in up to 43% of kidney allograft biopsies at one-year after transplantation and is associated with inferior graft function and poor graft survival. We studied [18F]-sodium fluoride ([18F]-NaF) imaging of microcalcifications in donor kidneys (n = 7) and explanted kidney allografts (n = 13). Three µm paraffin-embedded serial sections were used for histological evaluation of calcification (Alizarin Red; Von Kossa staining) and ex-vivo [18F]-NaF autoradiography. The images were fused to evaluate if microcalcification areas corresponded with [18F]-NaF uptake areas. Based on histological analyses, tubulointerstitial and glomerular microcalcifications were present in 19/20 and 7/20 samples, respectively. Using autoradiography, [18F]-NaF uptake was found in 19/20 samples, with significantly more tracer activity in kidney allograft compared to deceased donor kidney samples (p = 0.019). Alizarin Red staining of active microcalcifications demonstrated good correlation (Spearman's rho of 0.81, p < 0.001) and Von Kossa staining of consolidated calcifications demonstrated significant but weak correlation (0.62, p = 0.003) with [18F]-NaF activity. This correlation between ex-vivo [18F]-NaF uptake and histology-proven microcalcifications, is the first step towards an imaging method to identify microcalcifications in active nephrocalcinosis. This may lead to better understanding of the etiology of microcalcifications and its impact on kidney transplant function.

Renal adaptive response to exposure to low doses of uranyl nitrate and sodium fluoride in mice.

BACKGROUND: Despite their differences in physicochemical properties, both uranium (U) and fluoride (F) are nephrotoxicants at high doses but their adverse effects at low doses are still the subject of debate. METHODS: This study aims to improve the knowledge of the biological mechanisms involved through an adaptive response model of C57BL/6 J mice chronically exposed to low priming doses of U (0, 10, 20 and 40 mg/L) or F (0, 15, 30 and 50 mg/L) and then challenged with acute exposure of 5 mg/kg U or 7.5 mg/kg NaF. RESULTS: We showed that an adaptive response occurred with priming exposures to 20 mg/L U and 50 mg/L F, with decreased levels of the biomarkers KIM-1 and CLU compared to those in animals that received the challenge dose only (positive control). The adaptive mechanisms involved a decrease in caspase 3/7 activities in animals exposed to 20 mg/L U and a decrease in in situ VCAM expression in mice exposed to 50 mg/L F. However, autophagy and the UPR were induced independently of priming exposure to U or F and could not be identified as adaptive mechanisms to U or F. CONCLUSION: Taken together, these results allow us to identify renal adaptive responses to U and F at doses of 20 and 50 mg/L, probably through decrease apoptosis and inflammatory cell recruitment.

18F-Sodium Fluoride Positron Emission Tomography Activity Predicts the Development of New Coronary Artery Calcifications.

OBJECTIVE: The coronary calcium score (CCS) predicts cardiovascular disease risk in individuals with diabetes, and rate of progression of CCS is an additional and incremental marker of risk. 18F-sodium fluoride positron emission tomography (18F-NaF PET) detects early and active calcifications within the vasculature. We aimed to ascertain the relationship between 18F-NaF PET activity and CCS progression in patients with diabetes. Approach and Results: We identified individuals between 50 and 80 years with diabetes and no history of clinical coronary artery disease. Those with a CCS ≥10 were invited to undergo 18F-NaF PET scanning and then repeat CCS >2 years later. 18F-NaF PET and CCS analysis were performed on a per-coronary and a per-patient level. We compared the proportion of CCS progressors in 18F-NaF PET-positive versus 18F-NaF PET-negative coronary arteries. Forty-one participants with 163 coronary arteries underwent follow-up CCS 2.8±0.5 years later. 18F-NaF PET-positive coronary arteries (n=52) were more likely to be CCS progressors, compared with negative coronary arteries (n=111; 86.5% versus 52.3%, P<0.001). Adjusting for baseline CCS, 18F-NaF PET-positive disease was an independent predictor of subsequent CCS progression (odds ratio, 2.92 [95% CI, 1.32-6.45], P=0.008). All subjects (100%, 15/15) with ≥2 18F-NaF-positive coronary arteries progressed in CCS. CONCLUSIONS: In subjects with diabetes, 18F-NaF PET positivity at baseline, independently predicted the progression of calcifications within the coronary arteries 2.8 years later. These findings suggest 18F-NaF PET may be a promising technique for earlier identification of patients at higher risk of cardiovascular events.

Degeneración valvular en pacientes con bioprótesis aórtica porcina evaluada mediante PET con 18Ffluoruro de sodio / Valve degeneration in patients with aortic porcine bioprosthesis evaluated through 18Fsodium fluoride PET / Degeneração valvular em pacientes com bioprótese aórtica suína avaliada mediante PET com fluoreto18F

Introducción: la degeneración valvular protésica es un problema clínico; los métodos de imagen convencionales permiten diagnosticarla en las últimas etapas. La tomografía por emisión de positrones (PET) con 18Ffluoruro puede detectar de manera precoz la degeneración subclínica. Objetivo: correlacionar parámetros de deterioro estructural protésico por PET con parámetros hemodinámicos ecocardiográficos al año de la sustitución valvular aórtica (SVA) por bioprótesis porcina. Métodos: estudio prospectivo ad hoc de un ensayo clínico. Se reclutaron pacientes sometidos a SVA por bioprótesis porcina en dos centros nacionales entre el 01/01/2019 y el 13/02/2020. Se realizaron controles clínicos y ecocardiográficos. Se seleccionaron aleatoriamente 19 sujetos a los que se les realizó PET 18Ffluoruro de sodio con angiotomografía al año de la SVA. Se midió la captación del trazador en la válvula (SUVavV) y aurícula derecha (SUVavA), calculando el índice SUVavV/SUVavA, que se comparó con los gradientes ecocardiográficos medio y máximo al año, mediante análisis de correlación de Spearman. Resultados: de 140 sujetos sometidos a SVA se realizó PET a 19, a los 16,3 meses (15,9-16,9) luego de la SVA. La mediana del índice SUVavV/SUVavA fue de 1,17 (1,11-1,27). Se encontró una correlación negativa moderada entre la captación de 18Ffluoruro y el gradiente medio (coeficiente de correlación -0,516, p = 0,028) y máximo (coeficiente -0,589, p = 0,010) al año. Conclusiones: en el seguimiento de los pacientes en los que se le realizó una sustitución valvular aórtica con bioprótesis, encontramos valores bajos de captación en el PET y gradientes ecocardiográficos normales con una correlación negativa moderada entre estos hallazgos

Introduction: prosthetic valve degeneration is a relevant clinical disorder; conventional imaging methods allow diagnosis in the later stages. 18Ffluoride positron emission tomography (PET) can detect subclinical degeneration earlier. Objective: correlate parameters of prosthetic structural deterioration by PET with echocardiographic hemodynamic parameters one year after aortic valve replacement (AVR) by porcine bioprosthesis. Methods: prospective ad hoc study of a clinical trial. Patients undergoing AVR by porcine bioprosthesis were recruited in two national centers between 01/01/2019 and 02/13/2020. Clinical and echocardiographic controls were carried out. 19 subjects were randomly selected and underwent 18Fsodium fluoride PET with CT angiography one year after AVR. Tracer uptake in the valve (SUVavV) and right atrium (SUVavA) was measured, creating the SUVavV/SUVavA index, which was compared with the mean and maximum gradients at one year, using Spearman's correlation analysis. Results: of a total of 140 subjects, PET was performed on 19 at 16.3 months (15.9-16.9) after the AVR. The median SUVavV/SUVavA ratio was 1.17 (1.11-1.27). A moderate negative correlation was found between. 18Ffluoride uptake and the mean gradient (correlation coefficient -0.516, p = 0.028) and maximum (coefficient of -0.589, p = 0.010) at one year. Conclusions: we found low uptake values in PET, echocardiographic gradients in normal range and no positive correlation between both parameters. It is the first national report with these imaging techniques

Introdução: a degeneração da válvula protética é um problema clínico; os métodos convencionais de imagem permitem o diagnóstico nas fases posteriores. A tomografia por emissão de pósitrons (PET) com fluoreto18F pode detectar a degeneração subclínica precocemente. Objetivo: correlacionar parâmetros de deterioração estrutural protética por PET com parâmetros hemodinâmicos ecocardiográficos após um ano da troca valvar aórtica (SVA) por bioprótese suína. Métodos: estudo ad hoc prospectivo de um ensaio clínico. Pacientes submetidos a SVA por bioprótese suína foram recrutados em dois centros nacionais entre 01/01/2019 e 13/02/2020. Foram realizados controles clínicos e ecocardiográficos. 19 indivíduos foram selecionados aleatoriamente que foram submetidos a PET com fluoreto de sódio 18F com angiotomografia um ano após AVS. A captação do traçador na válvula (SUVavV) e átrio direito (SUVavA) foi medida, criando o índice SUVavV/SUVavA, que foi comparado com os gradientes médio e máximo em um ano, usando a análise de correlação de Spearman. Resultados: de um total de 140 indivíduos submetidos a SVA, PET foi realizado em 19, em 16,3 meses (15,9-16,9) após a SVA. A proporção média de SUVavV/SUVavA foi de 1,17 (1,11-1,27). Uma correlação negativa moderada foi encontrada entre a captação de fluoreto18F e o gradiente médio (coeficiente de correlação -0,516, p = 0,028) e máximo (coeficiente de -0,589, p = 0,010) em um ano. Conclusões: encontramos valores baixos de captação na PET, gradientes ecocardiográficos dentro da normalidade, sem correlação positiva entre os dois parâmetros. É o primeiro trabalho nacional com essas técnicas de imagem

Remineralising Dentine Caries Using Sodium Fluoride with Silver Nanoparticles: An In Vitro Study.

OBJECTIVE: To investigate the remineralizing and staining effects of sodium fluoride (NaF) solution with polyethylene glycol-coated silver nanoparticles (PEG-AgNPs) on artificial dentine caries. MATERIALS AND METHODS: Demineralized human dentine blocks were allocated to three groups. The blocks in group 1 underwent a topical application of a 12% silver diamine fluoride (SDF, 14,150 ppm fluoride) solution. The blocks in group 2 received a topical application of a 2.5% NaF (11,310 ppm fluoride) with PEG-AgNPs (400 ppm silver). The blocks in group 3 received deionized water. All blocks were subjected to pH cycling for 8 days. The surface morphology and cross-sectional features were investigated using scanning electron microscopy (SEM). The color parameters, crystal characteristics, lesion depth, and collagen degradation of the blocks were assessed using digital spectrophotometry, X-ray diffraction (XRD), micro-computed tomography, and spectrophotometry with a hydroxyproline assay, respectively. RESULTS: The SEM showed that dentine collagen was exposed in group 3 but not in groups 1 and 2. The mean lesion depths in groups 1 to 3 were 118±7 µm, 121±14 µm, and 339±20 µm, respectively (groups1,2<3; p<0.001). The data indicated that fluoridated PEG-AgNPs introduced no significant color effect on dentine, but SDF caused distinct discoloration. The XRD indicated that silver chloride was formed in group 1, and fluorapatite was detected in groups 1 and 2. The concentration of hydroxyproline liberated from collagen was significantly less in groups 1 and 2 than in group 3. CONCLUSION: The use of NaF solution with PEG-AgNPs can remineralize artificial dentine caries and inhibit collagen degradation without causing significant tooth staining.

18F-Sodium Fluoride (18F-NaF) for Imaging Microcalcification Activity in the Cardiovascular System.

Accumulating preclinical and clinical evidence suggests that calcification is one of the body's primary responses to injury and a key pathological feature of cardiovascular disease. Calcification activity can now be imaged using 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) in combination with either computed tomography or magnetic resonance. These techniques allow visualization of calcification activity and, therefore, provide different information to the established macroscopic calcium imaged with computed tomography. Indeed, 18F-NaF PET has been used to investigate a wide range of valvular conditions, including aortic stenosis, mitral annular calcification, and bioprosthetic valve disease, as well as vascular conditions, including abdominal aortic aneurysm disease, coronary, and carotid atherosclerosis, peripheral vascular disease, and erectile dysfunction. In this brief review, we will focus on how 18F-NaF PET has improved our pathophysiological understanding of cardiovascular calcification and how it can be used as a marker of vascular calcification, providing a useful tool that can be utilized in clinical trials investigating the prediction of both disease progression and clinical events. Finally, we will discuss how 18F-NaF might be employed clinically to improve patient assessment and to guide decision-making.

Aortic valve microcalcification and cardiovascular risk: an exploratory study using sodium fluoride in high cardiovascular risk patients.

18F-sodium fluoride (18F-NaF) has been used to access aortic stenosis in clinical research setting. It is known that its uptake is related with microcalcification. The purpose of this study was to assess the relationship between 18F-NaF uptake by the aortic valve and cardiovascular risk. Twenty-five patients with risk factors for cardiovascular disease, without known cardiovascular disease or aortic stenosis underwent PET-CT with 18F-NaF. Cardiovascular risk was assessed through the ASCVD (Atherosclerotic Cardiovascular Disease) risk calculator. Aortic valve 18F-NaF (AoVCUL) uptake was evaluated through the corrected uptake per lesion (CUL = max SUV - mean blood-pool SUV). Calcium score was obtained through cardiac CT. The patients present a mean age of 63.90 ± 8.60 years and 56% males. The mean ASCVD was of 28.76 ± 18.96 (M 25, IQR 38.50). The mean aortic valve calcium score (AoVCaSc) was of 53.24 ± 164.38 (M 6; IQR 29.75) and the AoVCUL was of 0.50 ± 0.10 (M 0.52, IQR 0.15). The patients were classified according to the ASCVD: patients with a risk greater or equal than the 50th percentile of the ASCVD risk and patients with a risk lower than the 50th percentile. The AoVCUL was evaluated in both groups: AoVCUL = 0.56 ± 0.10 vs 0.42 ± 0.15, p = 0.02; AoVCaSc was of 0 in 11 patients (44%) and those with an ASCVD greater or equal than the 50th percentile had a mean AoVCaSc of 8.00 ± 13.80, and those with an ASCVD risk lower than the 50th percentile had a mean AoVCaSc of 95.00 ± 223.45; p = 0.09. In this study microcalcification, evaluated through 18F-NaF on PET-CT, was related with cardiovascular risk. Although the score of calcium seems to be higher in higher cardiovascular risk patients, no significant difference was found between groups.

La exposición prenatal a fluoruro induce cambios en la porción coronal de la cripta ósea y altera la erupción dental en crías lactantes / Prenatal fluoride exposure induces changes in the coronal portion of bony crypt and alters dental eruption in suckling rats

La erupción dental es un proceso estrictamente regulado y programado espacial y temporalmente. El objetivo del trabajo fue estudiar el efecto de la exposición prenatal a fluoruro de sodio (NaF) sobre los eventos morfológicos y celulares que ocurren en el hueso supracoronal del primer molar de crías de rata durante la etapa preeruptiva. Se emplearon crías (n=6-8 por grupo) provenientes de madres que bebieron crónicamente agua con diferentes concentraciones de F- en forma de NaF durante la gestación y lactancia: control y NaF (50 mg/L). En cortes histológicos de la mandíbula de crías de 3 y 10 días se analizaron parámetros de histomorfometría estática en la zona supracoronal de la canastilla ósea a la altura del primer molar inferior: volumen óseo trabecular [BV/TV (%)], número de osteoclastos por milímetro (N.Oc/mm) y las variables indirectas: número de trabéculas [Tb.N (1/mm)], espesor [Tb.Th (µm)] y separación trabecular [Tb.Sp (µm)]. En crías de 15 días se midió el grado de erupción [TED (µm)] del primer molar inferior. Los resultados se analizaron con el test "t" de Student considerando diferencias significativas a p<0,05. El análisis histomorfométrico demostró un incremento en el BV/TV (%) del hueso supracoronal (p<0,01) asociado con disminución del N.Oc/mm (p<0,01) en crías de 3 y 10 días expuestas prenatalmente al F-. El grado de erupción dental fue menor en animales expuestos prenatalmente al F- en comparación con los controles (p<0,01). En conclusión, los resultados observados en la mandíbula de crías expuestas durante la etapa prenatal y posnatal temprana al F- sugieren un efecto disruptivo sobre la actividad resortiva necesaria para formación del canal eruptivo. (AU)

Tooth eruption is a tightly regulated and spatially and temporally programmed process. The aim of this study was to examine the effect of prenatal NaF exposure on the morphological and cellular events that occur in the supracoronal area of bony crypt of the first rat molar during the preeruptive stage. Offspring from two groups of rats were used (6-8 per group): Control and 50 mg/L NaF. The treatment was performed during pregnancy and lactation. Suckling pups were euthanized at 3-, 10- and 15-days-old by cervical dislocation. Mandibles were removed and histologically processed to obtain buccolingual sections stained with H&E. In sections of first mandibular molar of 3- and 10-days-old pups, the following static histomorphometric parameters were evaluated: trabecular bone volume [BV/TV (%)] and number of osteoclasts (N.Oc/mm). Also, indirect parameters were obtained: trabecular number [Tb.N (1/mm)], trabecular thickness [Tb.Th (µm)], and trabecular separation [Tb.Sp (µm)]. The degree of tooth eruption [TED (µm)] was determined. Results are expressed as mean ± SE and analyzed by Student t-test. Histomorphometric analysis showed an increase in the BV/TV (%) of the bone crypt of 3- and 10- days-old pups exposed to NaF (p <0.01); this increase was associated with a decrease in the N.Oc/mm (p <0.01). TED of mandibular first molar was lower in prenatal NaF exposed group than in control group (p<0.01). In conclusion, the increased BV/TV and the lower N.Oc observed in the bone crypt of 3- and 10- days-old pups from mothers treated with NaF suggested a disruptive effect triggered by F- on the formation events of the eruptive pathway in the offspring. (AU)

Comparison of 18F-sodium fluoride PET/CT, 18F-fluorocholine PET/CT and diffusion-weighted MRI for the detection of bone metastases in recurrent prostate cancer: a cost-effectiveness analysis in France.

BACKGROUND: The diagnostic performance of 18F-sodium fluoride positron emission tomography/computed tomography (PET/CT) (NaF), 18F-fluorocholine PET/CT (FCH) and diffusion-weighted whole-body magnetic resonance imaging (DW-MRI) in detecting bone metastases in prostate cancer (PCa) patients with first biochemical recurrence (BCR) has already been published, but their cost-effectiveness in this indication have never been compared. METHODS: We performed trial-based and model-based economic evaluations. In the trial, PCa patients with first BCR after previous definitive treatment were prospectively included. Imaging readings were performed both on-site by local specialists and centrally by experts. The economic evaluation extrapolated the diagnostic performances of the imaging techniques using a combination of a decision tree and Markov model based on the natural history of PCa. The health states were non-metastatic and metastatic BCR, non-metastatic and metastatic castration-resistant prostate cancer and death. The state-transition probabilities and utilities associated with each health state were derived from the literature. Real costs were extracted from the National Cost Study of hospital costs and the social health insurance cost schedule. RESULTS: There was no significant difference in diagnostic performance among the 3 imaging modalities in detecting bone metastases. FCH was the most cost-effective imaging modality above a threshold incremental cost-effectiveness ratio of 3000€/QALY when imaging was interpreted by local specialists and 9000€/QALY when imaging was interpreted by experts. CONCLUSIONS: FCH had a better incremental effect on QALY, independent of imaging reading and should be preferred for detecting bone metastases in patients with biochemical recurrence of prostate cancer. TRIAL REGISTRATION: NCT01501630. Registered 29 December 2011.

Vascular Positron Emission Tomography and Restenosis in Symptomatic Peripheral Arterial Disease: A Prospective Clinical Study.

OBJECTIVES: This study determined whether in vivo positron emission tomography (PET) of arterial inflammation (18F-fluorodeoxyglucose [18F-FDG]) or microcalcification (18F-sodium fluoride [18F-NaF]) could predict restenosis following PTA. BACKGROUND: Restenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty. METHODS: In this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent 18F-FDG and 18F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months. RESULTS: Forty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation (18F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p < 0.001) and microcalcification (18F-NaF TBR 2.61 [IQR: 2.50 to 2.77] vs. 1.69 [IQR: 1.54 to 1.77]; p < 0.001) were higher in patients who developed restenosis. The predictive value of both 18F-FDG (cut-off TBRmax value of 1.98) and 18F-NaF (cut-off TBRmax value of 2.11) uptake demonstrated excellent discrimination in predicting 1-year restenosis (Kaplan Meier estimator, log-rank p < 0.001). CONCLUSIONS: Baseline and persistent femoral arterial inflammation and micro-calcification are associated with restenosis following lower limb PTA. For the first time, we describe a method of identifying complex metabolically active plaques and patients at risk of restenosis that has the potential to select patients for intervention and to serve as a biomarker to test novel interventions to prevent restenosis.

Sodium Fluoride and Fluoride Contaminated Ground Water Induced Altered Reproductive Performances in Male Rats.

Present study was undertaken to investigate the toxic effect of sodium fluoride (NaF)- and fluoride (F)-contaminated ground water on reproductive performances of male rats. Healthy adult male rats were categorised into three groups, first group of rats were served as control, whereas second group of rats were orally intubated with NaF (10 mg/kgbw/1 ml/rat) and third group of rats were allowed to drink F-contaminated ground water (5 mg/L) through drinking water bottles for 52 days. Exposure of NaF- and F-contaminated ground water caused significant decline in sperm motility, serum concentration of testosterone, and increase in sperm abnormality compared with controls. Further, significant histological alterations characterized with shrunken seminiferous tubules and degeneration of different stages of spermatogonial cells were observed in rats treated with NaF- and F-contaminated ground water. After the confirmation of toxic effect of F, these NaF- and F-contaminated ground water-treated male rats were allowed to mate with proven fertile untreated female rats to study the reproductive performances of male rats. There was a decline in parturition index, fertility index of male and female, gestation index and number of pups delivered in NaF-treated male rats compared with controls. However, gestation index and number of pups delivered were declined in F-contaminated ground water-treated male rats compared with controls. These results clearly indicate that F exposure affected the reproductive performances of male rats. The present study further revealed the fact that F-induced decline in testosterone levels, reduced sperm motility, and loss of spermatogonial cells affected the reproductive performances of male rats.

Fluoride Compromises Testicular Redox Sensor, Gap Junction Protein, and Metabolic Status: Amelioration by Melatonin.

The excess fluoride intake has been shown to adversely affect male reproductive health. The aim of the present study was to investigate the key mechanism underlying fluoride-induced testicular dysfunction and the role of melatonin as a modulator of testicular metabolic, oxidative, and inflammatory load. The present results indicated that sodium fluoride (NaF) exposure to adult male golden hamsters severely impairs reproductive physiology as evident from markedly reduced sperm count/viability, testosterone level, androgen receptor (AR), testicular glucose transporter (GLUT-1), gap junction (connexin-43), and survival (Bcl-2) protein expression. NaF exposure markedly increased testicular oxidative load, inflammatory (NF-kB/COX-2), and apoptotic (caspase-3) protein expression. However, melatonin treatment remarkably restored testicular function as evident by normal histoarchitecture, increased sperm count/viability, enhanced antioxidant enzyme activities (SOD and Catalase), and decreased lipid peroxidation (LPO) level. In addition, melatonin treatment upregulated testicular Nrf-2/HO-I, SIRT-1/ FOXO-1, and downregulated NF-kB/COX-2 expression. Further, melatonin ameliorated NaF-induced testicular metabolic stress by modulating testicular GLUT-1expression, glucose level, and LDH activity. Furthermore, melatonin treatment enhanced testicular PCNA, Bcl-2, connexin-43, and reduced caspase-3 expression. In conclusion, we propose the molecular mechanism of fluoride-induced testicular damages and ameliorative action(s) of melatonin.

Fluoride-Induced Alteration in the Diversity and Composition of Bacterial Microbiota in Mice Colon.

Fluoride, as an environmental toxin, causes damage to intestinal mucosa. It may promote pathogen infection by increasing the intestinal mucosa permeability. In this study, the colonic fecal samples from the control group (C group, 0 mg/L NaF for 60 days) and the fluoride group (F group, 100 mg/L NaF for 60 days) were subjected to high-throughput 16S rRNA sequencing to verify the effects of fluoride on the colonic flora of animals. Results revealed a total of 253 operative taxonomical units (OTUs) in two groups, and 22 unique OTUs occurred in the F group. Fluoride increased the microbiota diversity and species richness of the colon. Concretely, the abundance of the Tenericutes was increased at the level of the phyla in the F group. In addition, in the F group, significant differences at the genus level were observed in Faecalibaculum, Alloprevotella, [Eubacterium]_xylanophilum_group, Prevotellaceae_UCG-001, and Ruminiclostridium_9, compared to the C group. Among them, except for the reduction in Faecalibaculum, the other four bacteria were increased in the F group. In summary, the intestinal microbial composition of mice was reconstituted by the presence of fluoride, and the significantly changing bacteria may partly account for the pathogenesis of fluoride-induced intestinal dysfunction.