Correlation of 18F-sodium fluoride uptake and radiodensity in extraosseous metastases of medullary thyroid carcinoma

ABSTRACT Objective: Although 18F-sodium fluoride (18F-NaF) uptake is frequently observed in extraosseous metastases of medullary thyroid carcinoma (MTC) with calcification, it can also occur in metastatic sites without visible calcium deposition, leading to the hypothesis that visually undetectable calcium accumulation may be responsible for this uptake. The aim of this study was to indirectly support this hypothesis by analyzing the correlation between the degree of 18F-NaF uptake and radiodensity in extraosseous MTC metastases, since calcium deposition can increase attenuation even when not visually detectable. Subjects and methods: Extraosseous metastatic lesions of 15 patients with MTC were evaluated using 18F-NaF positron-emission tomography (PET)/computed tomography (CT) and segmented by levels of standardized uptake value (SUV). The correlation between mean SUV and mean Hounsfield unit (HU) values was assessed for the entire group of segments and for two subgroups with different mean HU values. Results: Very high correlations were observed between mean SUV and mean HU values for both the entire group of segments and the subgroup with a mean HU value greater than 130 (p = 0.92 and p = 0.95, respectively; p < 0.01). High correlation (p = 0.71) was also observed in the subgroup with mean HU values ranging from 20 to 130 (p < 0.01). Conclusion: The findings of the present study suggest that there is an association between 18F-NaF uptake and calcium deposition in extraosseous metastases of MTC, supporting the hypothesis that visually undetectable calcium accumulation may be responsible for 18F-NaF uptake in regions without visible calcium deposition.

Comparative Fluoride Release in Commonly Used Topical Fluoride Agents – An In Vitro Study

Background: Fluoride, the pivot of preventive dentistry, continues to be the ideal agent for modern caries prevention philosophy. Differential release of fluoride has implications on cariostatic property of the commercially available materials and thus indicating the importance of fluoride release after the application. Therefore the objective of this study was to assess the difference in fluoride release from the commercially available NaF, SnF2 and APF as compared to controls at different time intervals. Methods: 40 caries free sound premolars were selected for the study and randomly divided into 4 groups (10 specimens each). Teeth specimens in each group were subjected to respective Fluoride treatment i.e. Group I (2% NaF), Group II (8% SnF2), Group III (1.23% APF) and Group IV (No Fluoride treatment). All specimens were immersed in deionized water and samples collected after 1 hour, 1 day and 1 week were subjected to Fluoride estimation. Results: At 1 hour time interval, highest amount of fluoride release ranging from 6.76 to 8.58 ppm was observed in Group II - SnF2 that was significantly higher than NaF and APF treated specimens. At 1-day time interval, Group II – SnF2 and Group III – APF showed a higher release of fluoride ranging from 0.81–0.93 and 0.61–0.79 ppm respectively. At 1-week time interval, the fluoride release almost reached baseline values in all the groups except in Group II – SnF2 that still maintained a high fluoride release ranging from 0.62–0.84 ppm. Conclusion: 8% SnF2 is expected to have greater anticaries potential than 2% NaF and 1.23% APF gel, due to its high fluoride releasing property for prolonged period of time.

Treatment Response Assessment of Skeletal Metastases in Prostate Cancer with ¹⁸F-NaF PET/CT / 대한핵의학회잡지

PURPOSE: To determine the utility of ¹⁸F-sodium fluoride positron emission tomography-computed tomography (¹⁸F-NaF PET/CT) in the imaging assessment of therapy response in men with osseous-only metastatic prostate cancer.METHODS: In this Institutional Review Board-approved single institution retrospective investigation, we evaluated 21 ¹⁸F-NaF PET/CTscans performed in 14 patients with osseous metastatic disease from prostate cancer and no evidence of locally recurrent or soft-tissue metastatic disease who received chemohormonal therapy. Imaging-based qualitative and semi-quantitative parameters were defined and compared with changes in serum PSA level.RESULTS: Qualitative and semi-quantitative image-based assessments demonstrated > 80% concordance with good correlation (SUV(max) κ = 0.71, SUVavg κ = 0.62, SUVsum κ = 0.62). Moderate correlation (κ = 0.43) was found between SUV(max) and PSA-based treatment response assessments. There was no statistically significant correlation between PSA-based disease progression and semi-quantitative parameters. Qualitative imaging assessment was moderately correlated (κ = 0.52) with PSA in distinguishing responders and non-responders.CONCLUSION: ¹⁸F-NaF PET/CT is complementary to biochemical monitoring in patients with bone-only metastases from prostate cancer which can be helpful in subsequent treatment management decisions.

Bone and Calcified Soft Tissue Metastases of Medullary Thyroid Carcinoma Better Characterized on ¹⁸F-Fluoride PET/CT than on ⁶⁸Ga-Dotatate PET/CT / 대한핵의학회잡지

Herein, we report a case of a 19-year-old man with multiple endocrine neoplasia type 2B (MEN2B) and medullary thyroid carcinoma (MTC) diagnosed when he was 12 years of age. The patient had previously undergone total thyroidectomy, cervical radiotherapy, and chemotherapy. He progressed with known bone, pulmonary, and lymph node metastases and was scanned with ¹⁸F-fluoride (¹⁸F-NaF) and ⁶⁸Ga-dotatate whole-body positron emission tomography/computed tomography (PET/CT) for metastatic disease monitoring.We found that the MTC bone metastases and soft tissue calcified metastases were better characterized on ¹⁸F-NaF PET/CT than on ⁶⁸Ga-dotatate PET/CT. This case illustrates that the ¹⁸F-NaF PET/CT could be helpful not only to the detection of bone metastases but also to the detection of calcified soft tissue metastases in patients with MTC.

Inguinal Herniation of Urinary Bladder on F-18 Sodium Fluoride (NaF) PET-CT / 대한핵의학회잡지

Inguinal herniation of urinary bladder is uncommon and usually an incidental finding in asymptomatic patients. In some of these patients, residual urine volume and consequently, urinary tracer activity can be higher in the herniated bladder than the native bladder, in which case interpretation can be challenging on conventional planar imaging.We describe an interesting case of physiological activity in a herniated bladder simulating a “tear-drop”. This case serves an important reminder that whilst F-18NaF PET-CT has a similar spectrum of urinary activity to conventional bone scintigraphy; morphological correlation on hybrid imaging is invaluable in ensuring the physiological nature of uptake.

Unusual Soft Tissue Uptake of F-18 Sodium Fluoride in Three Patients Undergoing F-18 NaF PET/CT Bone Scans for Prostate Cancer / 대한핵의학회잡지

Three males aged 71 to 80 years with known stage IV metastatic prostate cancer underwent F-18 sodium fluoride (NaF) PET/CT to assess osseous metastatic disease burden and stability. In addition to F-18 NaF avid known osseous metastases, each patient also exhibited increased F-18 NaF activity in soft tissues. The first patient exhibited multiple F-18 NaF avid enlarged retroperitoneal and pelvic lymph nodes on consecutive PET/CT scans. The second patient demonstrated an F-18 NaF avid thyroid nodule on consecutive PET/CT scans. The third patient exhibited increased F-18 NaF activity in a hepatic metastasis.

An in vitro study of re-mineralization of enamel with early caries in primary teeth treated by NaF-chitosan gel / 实用口腔医学杂志

Objective:To estimate the remineralization of enamel of primary teeth with early caries protreated by NaF-chitosan gel.Methods:Early stage caries was created on anterior primary teeth.The samples were divided into 4 groups randomly (n =6),and treated by NaF-chitosan gel,chitosan gel,duraphat and non-treatment(the control) respectively.Then all samples were underwent a 7days pH cycle.Then samples were tested with SEM and EDS.Data were analyzed with SPSS 19.Results:The SEM data showed that chitosan gel protected the enamel surface from being mined by erosion.NaF-chitosan gel group showed more mineral crystal formation on the enamel surface.The NaF-chitosan gel group showed more Ca remineralized on the enamel surface.Conclusion:NaF-chitosan gel can increase the remineraliztion of on the anterior primary teeth with early stage caries.

Effects of dentifrice containing 1,500 ppm F (NaF) on dental erosion / 대한구강보건학회지

OBJECTIVES: The purpose of this study was to evaluate the effect of a dentifrice containing 1,500 ppm F (NaF) and 2% bamboo salt on dental erosion caused by ingestion of acidic beverages. METHODS: Specimens of extracted bovine teeth enamel were embedded in a resin and polished. Experimental specimens were subjected to one of the six treatments (n=10 per treatment group): the experimental group consisted of 1,500 ppm F (NaF)+2% bamboo salt; 1,500 ppm F (NaF); 1,000 ppm F (NaF)+2% bamboo salt; 1,000 ppm F (NaF); free fluoride+2% bamboo salt; and free fluoride. The specimens were exposed to the experimental dentifrice, an acidic beverage, and artificial saliva. The treated specimens were analyzed using a Vickers surface hardness test and scanning electron microscopy (SEM). Surface hardness and SEM were compared before and after the chemical pH cycling sequences for 12 days. RESULTS: Group 1 (1,500 ppm F+2% bamboo salt) showed the highest surface hardness, followed by group 2 (1,500 ppm F), group 3 (1,000 ppm F+2% bamboo salt), group 4 (1,000 ppm F), group 5 (free fluoride+2% bamboo salt), and group 6 (free fluoride), in that order. Upon observing the surface by SEM, when bamboo salt was used and when the NaF concentration was higher, the enamel was denser and the surface was more highly remineralized. CONCLUSIONS: The use of a higher concentration of NaF and bamboo salt resulted in a higher preventive effect on tooth erosive potential. The addition of bamboo salt to dentifrice containing a high concentration of NaF can contribute to preventing dental erosion.

Receiver operating characteristic (ROC) curve for classification of18F-NaF uptake on PET/CT / Curva de característica de operação do receptor (ROC) para classificação da captação de 18F-NaF em PET/CT

Abstract Objective: To assess the cutoff values established by ROC curves to classify18F-NaF uptake as normal or malignant. Materials and Methods: PET/CT images were acquired 1 hour after administration of 185 MBq of18F-NaF. Volumes of interest (VOIs) were drawn on three regions of the skeleton as follows: proximal right humerus diaphysis (HD), proximal right femoral diaphysis (FD) and first vertebral body (VB1), in a total of 254 patients, totalling 762 VOIs. The uptake in the VOIs was classified as normal or malignant on the basis of the radiopharmaceutical distribution pattern and of the CT images. A total of 675 volumes were classified as normal and 52 were classified as malignant. Thirty-five VOIs classified as indeterminate or nonmalignant lesions were excluded from analysis. The standardized uptake value (SUV) measured on the VOIs were plotted on an ROC curve for each one of the three regions. The area under the ROC (AUC) as well as the best cutoff SUVs to classify the VOIs were calculated. The best cutoff values were established as the ones with higher result of the sum of sensitivity and specificity. Results: The AUCs were 0.933, 0.889 and 0.975 for UD, FD and VB1, respectively. The best SUV cutoffs were 9.0 (sensitivity: 73%; specificity: 99%), 8.4 (sensitivity: 79%; specificity: 94%) and 21.0 (sensitivity: 93%; specificity: 95%) for UD, FD and VB1, respectively. Conclusion: The best cutoff value varies according to bone region of analysis and it is not possible to establish one value for the whole body.

Resumo Objetivo: Acessar valores de corte estabelecidos pela curva ROC para classificar a captação de 18F-NaF como normal ou maligna. Materiais e Métodos: Imagens de PET/CT foram realizadas 1 hora após a administração de 185 MBq de18F-NaF e volumes de interesse (VOIs) foram desenhados em três regiões do esqueleto: diáfise umeral proximal direita (UD), diáfise femoral proximal direita (FD) e corpo da primeira vértebra lombar (VB1), em 254 pacientes, totalizando 762 VOIs. A captação nos VOIs foi classificada como normal ou maligna baseada no padrão de distribuição do radiofármaco e nas imagens de CT. Um total de 675 volumes foi classificado como normais e 52 como malignos. Trinta e cinco VOIs classificados como indeterminados ou lesões não malignas foram excluídos da análise. Os valores de captação (SUVs) medidos nos VOIs foram plotados em uma curva ROC para cada uma das três regiões. Foi calculada a área sob a curva (AUC), bem como os valores de SUV mais adequados para a classificação dos VOIs (maior resultado da soma da sensibilidade e especificidade). Resultados: As AUCs foram 0,933, 0,889 e 0,975 para UD, FD e VB1, respectivamente. Os valores de corte mais adequados de SUV foram 9,0 (sensibilidade: 73%; especificidade: 99%), 8,4 (sensibilidade: 79%; especificidade: 94%) e 21,0 (sensibilidade: 93%; especificidade: 95%)para UD, FD e VB1, respectivamente. Conclusão: O valor de corte de SUV mais adequado varia de acordo com a região óssea em análise e não é possível estabelecer um valor adequado para todo o esqueleto.

The role of low dose CT as part of the same 18F-NaF PET/CT in detecting bone metastases in lung cancer / 实用医学杂志

Objective Retrospectively evaluate low dose computed tomography (CT) as part of a combined 18F-NaF positron emission tomography (18F-NaFPET/CT) examination in lung cancer patients suspected of bone metastases. Methods 118 of 122 lesions with increased uptake of 18F-NaF were assessed. Characteristics of bone metastases on CT images were reviewed by radiologists. Results 27 of 47 metastases presented as sites of increased uptake with corresponding lytic or sclerotic changes on low dose CT. Other 20 show normal or non-specific appearing bone on CT. Most benign lesions (67 of 71,94%)have a benign appearance on low-dose CT. Conclusions Low dose CT images were useful in precisely diagnosing bone metastasis. Negative low dose CT appearance to the abnormal foci on PET may be a reliable sign of metastases.

Prevalence of exclusive lower extremity metastases at 18F-NaF PET/CT / Prevalência de metástases exclusivas em membros inferiores em exames de PET/TC com 18F-NaF

Abstract Objective: To evaluate the prevalence of exclusive lower extremity metastases, specifically in the femur and below the knee, observed at 18F-NaF PET/CT. Materials and Methods: One thousand consecutive PET/CT studies were retrospectively evaluated for the presence of exclusive uptake in lower extremities suggesting metastatic involvement. The presumptive diagnoses based on such uptakes were subsequently obtained by evaluation of other imaging studies. Results: No exclusive uptake suggestive of metastasis below the femur was observed in the present series. Exclusive uptake was observed in the proximal femur with a presumptive diagnosis of metastasis in two patients. Conclusion: The prevalence of exclusive metastasis below the femur is low and scanning from head to knees is appropriate in most cases. .

Resumo Objetivo: Avaliar a prevalência de metástases exclusivas em membros inferiores, subdivididas em lesões femorais e abaixo dos joelhos, em exames de PET/TC com 18F-NaF. Materiais e Métodos: Mil exames consecutivos foram retrospectivamente avaliados para a presença de captações exclusivas em membros inferiores sugestivas de comprometimento metastático. Os diagnósticos presuntivos dessas captações foram posteriormente obtidos pela avaliação de outros exames realizados. Resultados: Não foram observadas captações exclusivas sugestivas de metástases abaixo dos fêmures na nossa casuística. Foi observada captação exclusiva no terço superior do fêmur com diagnóstico de metástase em dois pacientes. Conclusão: A prevalência de metástase exclusiva abaixo dos fêmures é baixa e a realização do exame da cabeça até os joelhos é adequada na maioria dos casos. .

Comparison of standardized uptake values measured on 18F-NaF PET/CT scans using three different tube current intensities / Comparação dos valores de captação medidos nos estudos de 18F-NaF PET/CT utilizando três intensidades diferentes de corrente do tubo de tomografia computadorizada

Objective: To analyze standardized uptake values (SUVs) using three different tube current intensities for attenuation correction on 18FNaF PET/CT scans. Materials and Methods: A total of 254 18F-NaF PET/CT studies were analyzed using 10, 20 and 30 mAs. The SUVs were calculated in volumes of interest (VOIs) drawn on three skeletal regions, namely, right proximal humeral diaphysis (RH), right proximal femoral diaphysis (RF), and first lumbar vertebra (LV1) in a total of 712 VOIs. The analyses covered 675 regions classified as normal (236 RH, 232 RF, and 207 LV1). Results: Mean SUV for each skeletal region was 3.8, 5.4 and 14.4 for RH, RF, and LV1, respectively. As the studies were grouped according to mAs value, the mean SUV values were 3.8, 3.9 and 3.7 for 10, 20 and 30 mAs, respectively, in the RH region; 5.4, 5.5 and 5.4 for 10, 20 and 30 mAs, respectively, in the RF region; 13.8, 14.9 and 14.5 for 10, 20 and 30 mAs, respectively, in the LV1 region. Conclusion: The three tube current values yielded similar results for SUV calculation. .

Objetivo: Analisar os valores de captação (SUVs) utilizando três diferentes intensidades de mAs para realização de correção de atenuação na 18F-NaF PET/CT. Materiais e Métodos: Um total de 254 exames de 18F-NaF PET/CT foi estudado utilizando 10, 20 e 30 mAs. Os SUVs foram calculados utilizando volumes de interesse (VOIs) desenhados em três regiões do esqueleto: diáfise proximal do úmero direito (UD), diáfise proximal do fêmur direito (FD) e primeira vértebra lombar (VB1), totalizando 712 VOIs. Desse total, 675 regiões classificadas como normal foram analisadas (236, 232 e 207 na UD, FD e VB1, respectivamente). Resultados: A média dos SUVs para cada região óssea foi 3,8, 5,4 e 14,4 para UD, FD e VB1, respectivamente. Quando os exames foram agrupados pelo valor da corrente mAs, a média de valores de captação foi 3,8, 3,9 e 3,7 para 10, 20 e 30 mAs, respectivamente, na UD; 5,4, 5,5 e 5,4 para 10, 20 e 30 mAs, respectivamente, na FD; e 13,8, 14,9 e 14,5 para 10, 20 e 30 mAs, respectivamente, na VB1. Conclusão: As três correntes analizadas apresentaram resultados similares para o cálculo de SUV. .

NaF-induced Autophagy on SCC25 Human Tongue Squamous Cell Carcinoma Cells

Fluoride has been accepted as an important material for oral health and is widely used to prevent dental caries in dentistry. However, its safety is still questioned by some. Autophagy has been implicated in cancer cell survival and death, and may play an important role in oral cancer. This study was undertaken to examine whether sodium fluoride (NaF) modulates autophagy in SCC25 human tongue squamous cell carcinoma cells. NaF demonstrated anticancer activity via autophagic and apoptotic cell death. Autophagic vacuoles were detectable using observed to form by monodansylcadaverine (MDC) and acridine orange (AO). Analysis of NaF-treated SCC25 cells for the presence of biochemical markers revealed direct effects on the conversion of LC-3II, degradation of p62/SQSTM1, cleavage formation of ATG5 and Beclin-1, and caspase activation. NaF-induced cell death was suppressed by the autophagy inhibitor 3-methyladenine (3-MA). NaF-induced autophagy was confirmed as a pro-death signal in SCC25 cells. These results implicate NaF as a novel anticancer compound for oral cancer therapy.

Effect of mouthrinse with low pH on the surface microhardness of artificial carious enamel / 대한구강보건학회지

OBJECTIVES: The aim of the present study was to evaluate the effect of fluoride mouthrinse with low pH on the surface microhardness of artificial incipient carious enamel. METHODS: Firstly, the concentration of sodium fluoride and pH values were measured in commercially available mouthrinse. Secondly, DOCTOR Clean & Fresh(R) (Jang In Pharm, co., LTD. KOREA) with 0.02% sodium fluoride and pH value below pH 4.0 was selected as the experimental group, 0.02% sodium as the positive control group and distilled water as the negative control group. Enamel samples of n vine teeth (n=36) were divided into the three groups respectively and treated with the mouthrinse solutions for 3 and 20 minutes. The surface microhardness (Vickers hardness number, VHN) was measured with microhardness tester before and after the treatments. RESULTS: The average pH of DOCTOR Clean & Fresh(R) was 3.45+/-0.00, and it was acidic enough to cause tooth erosion. The difference of surface microhardness (DeltaVHN) before and after the 20 minute treatment was statistically significant among the groups: DOCTOR Clean & Fresh(R) (12.77+/-2.25 DeltaVHN), distilled water (0.24+/-0.75 DeltaVHN), 0.02% sodium fluoride solution (-0.62+/-1.62 DeltaVHN) (P<0.05). The DOCTOR Clean & Fresh(R) group with low pH showed greater changes on the surface microhardness of the carious enamel than those of other groups (P<0.05). CONCLUSIONS: It is suggested that the mouthrinse with low pH can reduce the surface microhardness of incipient carious enamel.

Mechanism Underlying NaF-induced Apoptosis and Cell Cycle Arrest on G361 Human Melanoma Cell Line / 체질인류학회지

Fluoride is widely used in dentistry to prevent dental caries, even though the safety of fluoride is a controversial issue. There are no known adverse effects of long-term fluoride ingestion for caries prevention, but an overdose can cause serious acute toxicity. Nevertheless it is accepted that fluoride is an important material for oral health. This study was undertaken to investigate the modulation of cell cycle-related proteins and apoptosis induction underlying mechanism by NaF treatment on G361 human melanoma cell line. The viability of G361 cells and the growth inhibition of G361 cells were assessed by MTT assay and clonogenic assay respectively. Hoechst staining, DNA electrophoresis and TUNEL staining were conducted to observe G361 cells undergoing apoptosis. G361 cells were treated with NaF, and Western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, MMP activity and proteasome activity were performed. NaF treatment in G361 cells resulted in a time- and does-dependent decrease of cell viability and a does-dependent inhibition of cell growth, and induced apoptotic cell death. And tested G361 cells showed several lines of apoptotic manifestation such as nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, the decrease of DNA contents, the release of cytochrome c into cytosol, the translocation of AIF and DFF40 (CAD) onto nuclei, a significant shift of Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-7, caspase-6, caspase-3, PARP, Lamin A/C and DFF45 (ICAD). Furthermore, NaF resulted in down-regulation of the G1 cell cycle-related proteins, and up-regulation of p53. Taken collectively, our present findings demonstrate that NaF strongly inhibits cell proliferation by modulating the expression of the G1 cell cycle-related proteins and induces apoptosis via proteasome, mitochondria and caspase cascades in G361 cells.

Mechanism Underlying NaF-Induced Apoptosis in Human Oral Squamous Cell Carcinoma

Few studies have evaluated the apoptosis-inducing efficacy of NaF on cancer cells in vitro but there has been no previous investigation of the apoptotic effects of NaF on human oral squamous cell carcinoma cells. In this study, we have investigated the mechanisms underlying the apoptotic response to NaF treatment in the YD9 human squamous cell carcinoma cell line. The viability of YD9 cells and their growth inhibition were assessed by MTT and clonogenic assays, respectively. Hoechst staining, DNA electrophoresis and TUNEL staining were conducted to detect apoptosis. YD9 cells were treated with NaF, and western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, and MMP and proteasome activity assays were performed sequentially. The NaF treatment resulted in a time- and dose-dependent decrease in YD9 cell viability, a dose-dependent inhibition of cell growth, and the induction of apoptotic cell death. The apoptotic response of these cells was manifested by nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, a significant shift of the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-3, PARP, Lamin A/C and DFF45 (ICAD). Furthermore, NaF treatment resulted in the downregulation of G1 cell cyclerelated proteins, and upregulation of p53 and the Cdk inhibitor p27KIP1. Taken collectively, our present findings demonstrate that NaF strongly inhibits YD9 cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via mitochondrial and caspase pathways.

Mechanism Underlying NaF-Induced Apoptosis in Human Oral Squamous Cell Carcinoma

Few studies have evaluated the apoptosis-inducing efficacy of NaF on cancer cells in vitro but there has been no previous investigation of the apoptotic effects of NaF on human oral squamous cell carcinoma cells. In this study, we have investigated the mechanisms underlying the apoptotic response to NaF treatment in the YD9 human squamous cell carcinoma cell line. The viability of YD9 cells and their growth inhibition were assessed by MTT and clonogenic assays, respectively. Hoechst staining, DNA electrophoresis and TUNEL staining were conducted to detect apoptosis. YD9 cells were treated with NaF, and western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, and MMP and proteasome activity assays were performed sequentially. The NaF treatment resulted in a time- and dose-dependent decrease in YD9 cell viability, a dose-dependent inhibition of cell growth, and the induction of apoptotic cell death. The apoptotic response of these cells was manifested by nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, a significant shift of the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-3, PARP, Lamin A/C and DFF45 (ICAD). Furthermore, NaF treatment resulted in the downregulation of G1 cell cyclerelated proteins, and upregulation of p53 and the Cdk inhibitor p27KIP1. Taken collectively, our present findings demonstrate that NaF strongly inhibits YD9 cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via mitochondrial and caspase pathways.

Protective effects of selenium on fluoride induced alterations in certain enzymes in brain of mice.

This study reports the protective effects of selenium on fluoride induced alterations in the activities of pro-oxidative (xanthine oxidase (XOD), lipid peroxidation (LPO) free radical scavenging, (catalase, superoxide dismutase (SOD), glutathione-s-transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione) and metabolic (glucose-6-phosphate dehydrogenase, alanine amino transferase (ALAT), aspartate aminotransferase (AAT), creatine phosphokinase (CPK), acid phosphatase (AP), alkaline phosphatase (ALP)] enzymes along with fluoride and selenium levels in brain of mice. Animals were divided into control, NaF treated group (20 mg kg-1 body wt.-1 intraperitonial) and Selenium+NaF treated group (sodium selenite, 5 mg of selenium / 0.2 ml distilled water kg-1 body wt.-1 day) and were maintained for 14 days on respective treatments. The decreased bodyweight (-11.35%) as well as organosomatic index (-15.1%) of brain in NaF group were recovered in treatment of selenium along with NaF. The increased accumulation of fluoride (32.1%) in brain observed in NaF treated group compared to control was diminished in selenium+NaF treated group. Selenium levels (3.03%) increased in selenium+NaF treated group in compared to decrement in NaF treatment. The SOD (-16.6%), Catalase (-21.5%), GST (-13.72%), GPX (-19.16%), GR (-44.97%) activities and Glutathione (-23%) content in NaF treated group were decreased significantly compared to controls, which were significantly (p<0.01) recovered in selenium+NaF group. Increased XOD (10.85%) and LPO (8.61%) levels observed in brain of NaF treated mice were reversed with selenium treatment. Glucose-6-phosphate dehydrogenase (-46.98%), ALAT (-10.44%), AAT (-10.21%), CPK (-27.98%) were decreased and alkaline phosphatase (10.6%), acid phosphatase (24.09%) increased in brain of mice after administration of NaF. All metabolic enzymes were significantly (p<0.01) reversed after administration of selenium to the NaF treated group. Thus, the adverse effects of NaF on oxidative and metabolic enzymes of brain were reversible with ameliorative action of selenium supplementation. As evident in this study, the antioxidative nature of selenium coupled with its reversal effect on metabolic enzymes in brain of mice treated with fluoride suggests its use as antidote agent against fluorosis.

Determinacion dll gasto energetico (ge) por el etodo factorial en patinadores Cubanos de velocidad / Determinatio of energetic waste by the factorial method in high velocity skiiers

Se estudiaron 4 varones y 5 hembras del equipo cubano de patinaje velocidad para estimar su estado nutricional, GE y establecer recomendaciones nutricionales. U n microciclo tipo de las etapas de preparación general (G) y especial (E) constituyó el marco de medición. El GE se determinó mediante método factorial. Se realizó estadística inferencial para considerar diferencias entre variables por sexo y etapas para p ≤ 0,05. Para calcular las recomendaciones nutricionales se estimó el NAF. Se observaron características morfológicas similares a las reportadas en patinadores colombianos, así como un IMC adecuado. El GE por entrenamiento fue significativamente diferente en las dos etapas y el GET fue superior en la de PG. Energéticamente, se observó tendencia a valores superiores en los hombres en todos los indicadores, excepto para las actividades discrecionales durante la etapa de PE y el NAF de ambas y las recomendaciones dependieron de la etapa de preparación de estos patinadores.

Four and five female and male speed roller skaters of Cuban team were studied for nutritional status and energy cost estimation even as energy recommendations. A microcycle type of general (G) and special (S) training phases was the frame for measuring. EC was determined by factorial method. Inferential statistics for estimating differences between variables by sex and phases of training was for p ≤ 0,05. In order to make energy recommendations a PAL was also estimated. Morphological characteristics were similar to those reported in Colombian roller skaters and BMI was adequate. Sport training energy cost was significantly different in both phases and TEC was higher in G. It was observed that male skaters showed a trend to have higher values for all variables with the exception of discretionary activities in S and PAL for both phases. Energy recommendations depended on training phase of speed roller skaters.

Involvement of Bcl-2 Family and Caspases Cascade in Sodium Fluoride-Induced Apoptosis of Human Gingival Fibroblasts

Sodium fluoride (NaF) has been shown to be cytotoxic and elicit inflammatory response in human. However, the cellular mechanisms underlying NaF-induced cytotoxicity in periodontal tissues have not yet been elucidated. This study is aimed to investigate the mechanisms of NaF-induced apoptosis in human gingival fibroblast (HGF). NaF decreased the cell viability of HGF in a dose- and time-dependent manner. NaF gave rise to apoptotic morphological changes including cell shrinkage, chromatin condensation, and DNA fragmentation. However, NaF did not affect the production of ROS. In addition, NaF augumented cytochrome c release from mitochondria into the cytosol, and enhanced caspase -9 and -3 activities., cleavage (85 kDa fragments) of poly (ADP-ribose) polymerase (PARP) and upregulation of voltage-dependent anion channel (VDAC) 1. These results demonstrated that NaF-induced apoptosis in HGF may be mediated with mitochondria. Furthermore, NaF elevated caspase-8 activity and upregulated Fas-ligand (Fas-L), suggesting involvement of death receptor mediated pathway in NaF-induced apoptosis. Expression of Bcl-2, an anti-apoptotic Bcl-2 family, was downregulated, whereas expression of Bax, a pro-apoptotic Bcl-2 family, was not affected in NaF-treated HGF. These results suggest that NaF induces apoptosis in HGF through both mitochondria- and death receptor-mediated pathway mediated by Bcl-2 family.