A comparative study of two mouthrinses on plaque and gingivitis in school children in the age group of 13-16 years in Bangalore city.

J Indian Soc Pedod Prev Dent. 2007 Jul-Sep;25(3):126-9

Authors: Jayaprakash K, Veeresha KL, Hiremath SS

Research and clinical evidence indicate that most forms of plaque associated periodontal disease start as inflammatory lesions of the gingiva which if left untreated, may progress and eventually involve and compromise the entire periodontal attachment apparatus of the affected teeth. A study was conducted to assess the effect of a mouthrinse containing chlorhexidine and sodium fluoride on plaque accumulation and gingivitis in comparison with a chlorhexidine mouthrinse alone in a group of school children aged 13-16 years in Bangalore city. This combination along with the well established effect of fluoride in the prevention of caries presents an important contribution to dental public health. The results suggest that the chlorhexidine-sodium fluoride mouthrinse potentially possesses a significant effect on inhibition of plaque accumulation and gingivitis. This combination along with the well-established effect of fluoride in the prevention of caries, presents an important contribution to dental public health.

PMID: 17951928 [PubMed - in process]

Study of changes in phosphate, calcium and fluoride ions in plaque and saliva after the administration of a fluoride mouth rinse.

J Indian Soc Pedod Prev Dent. 2007 Jul-Sep;25(3):122-5

Authors: Poureslami HR, Torkzadeh M, Sefadini MR

In this study, the effects of 0.2% sodium fluoride mouthwash solution on calcium, phosphate and fluoride ion contents of saliva and microbial plaque was assessed. Fourteen volunteer students (7-12 years of age) of a boarding educational centre in Kerman City (Iran) were selected and under defined conditions, their saliva and plaque samples were collected. The concentrations of fluoride, calcium and phosphate ions of the samples were determined, and after 14 days, under the same conditions, the students were asked to rinse their mouth with 0.2% sodium fluoride mouthwash solution. The second set of saliva and plaque samples were collected and the concentrations of the ions were determined. Data was analyzed using paired t-test and the results were presented as tables. P < 0.05 was considered as statistically significant. After using 0.2% sodium fluoride mouthwash solution, a significant increase was observed in the F 2 ion concentration both plaque ( P P < 0.000) of all the studied subjects, while the concentration of phosphate decreased in both saliva and plaque; however, this decrease was significant only in plaque ( P < 0.01). The calcium ion concentration decreased in both plaque and saliva; however, in none of them, the decrease was significant ( P> 0.09 and P> 0.2, respectively).

PMID: 17951927 [PubMed - in process]

Salmeterol and cytokines modulate inositol-phosphate signalling in human airway smooth muscle cells via regulation at the receptor locus.

Respir Res. 2007;8:68

Authors: Smith N, Browning CA, Duroudier N, Stewart C, Peel S, Swan C, Hall IP, Sayers I

BACKGROUND: Airway hyper-responsiveness (AHR) is a key feature of asthma and a causal relationship between airway inflammation and AHR has been identified. The aim of the current study was to clarify the effect of proinflammatory cytokines and asthma medication on primary human airway smooth muscle (ASM) inositol phosphate (IPx) signalling and define the regulatory loci involved. METHODS: Primary Human ASM cells were isolated from explants of trachealis muscle from individuals with no history of respiratory disease. The effect of cytokine or asthma medication on histamine or bradykinin induced IPx signalling was assessed by [3H] inositol incorporation. Quantitative Real Time PCR was used to measure mRNA levels of receptors and downstream signalling components. Transcriptional mechanisms were explored using a combination of 5'Rapid Amplification of cDNA Ends (5'RACE) and promoter-reporter techniques. RESULTS: Treatment of Human ASM cells with IL-13, IFN gamma or salmeterol for 24 hours lead to a modest augmentation of histamine induced IPx responses (144.3 +/- 9.3, 126.4 +/- 7.5 and 117.7 +/- 5.2%, p < 0.05). Similarly, TNFalpha, IFN gamma or salmeterol treatment augmented bradykinin induced IPx responses (127.4 +/- 8.3, 128.0 +/- 8.4 and 111.7 +/- 5.0%, P < 0.05). No treatment significantly influenced sodium fluoride induced IPx responses suggesting regulation occurs at the receptor locus. Analyses of mRNA expression of components of the IPx pathway i.e. H1 Histamine Receptor (HRH1), B2 Bradykinin Receptor (BDKRB2), G alpha q/11 and PLC-beta1 identified that a significant induction of receptor mRNA (>2 fold) was a feature of these responses explaining the cytokine and spasmogen specificity. The HRH1 and BDKRB2 promoter regions were mapped in ASM and promoter-reporter analyses identified that salmeterol can induce HRH1 (>2 fold) and BDKRB2 (2-5 fold) transcription. The effect of cytokines on HRH1 and BDKRB2 promoter-reporter expression suggested a more complex regulation of mRNA expression involving additional loci to the core promoter. CONCLUSION: Our results indicate that the spasmogen specific receptor locus may be a key site of regulation determining the magnitude of spasmogen mediated ASM IPx responses during airway inflammation or following asthma medication. These data provide further insight into the molecular basis of AHR and extend our understanding of potentially detrimental effects associated with existing therapies used in the treatment of asthma.

PMID: 17903241 [PubMed - in process]

Endothelium-dependent and -independent hepatic artery vasodilatation is not impaired in a canine model of liver ischemia-reperfusion injury.

Braz J Med Biol Res. 2007 Jun;40(6):857-65

Authors: Miranda LC, Viaro F, Ceneviva R, Evora PR

We investigated whether hepatic artery endothelium may be the earliest site of injury consequent to liver ischemia and reperfusion. Twenty-four heartworm-free mongrel dogs of either sex exposed to liver ischemia/reperfusion in vivo were randomized into four experimental groups (N = 6): a) control, sham-operated dogs, b) dogs subjected to 60 min of ischemia, c) dogs subjected to 30 min of ischemia and 60 min of reperfusion, and d) animals subjected to 45 min of ischemia and 120 min of reperfusion. The nitric oxide endothelium-dependent relaxation of hepatic artery rings contracted with prostaglandin F2a and exposed to increasing concentrations of acetylcholine, calcium ionophore A23187, sodium fluoride, phospholipase-C, poly-L-arginine, isoproterenol, and sodium nitroprusside was evaluated in organ-chamber experiments. Lipid peroxidation was estimated by malondialdehyde activity in liver tissue samples and by blood lactic dehydrogenase (LDH), serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) activities. No changes were observed in hepatic artery relaxation for any agonist tested. The group subjected to 45 min of ischemia and 120 min of reperfusion presented marked increases of serum aminotransferases (ALT = 2989 +/- 1056 U/L and AST = 1268 +/- 371 U/L; P < 0.01), LDH = 2887 +/- 1213 IU/L; P < 0.01) and malondialdehyde in liver samples (0.360 +/- 0.020 nmol/mgPT; P < 0.05). Under the experimental conditions utilized, no abnormal changes in hepatic arterial vasoreactivity were observed: endothelium-dependent and independent hepatic artery vasodilation were not impaired in this canine model of ischemia/reperfusion injury. In contrast to other vital organs and in the ischemia/reperfusion injury environment, dysfunction of the main artery endothelium is not the first site of reperfusion injury.

PMID: 17581686 [PubMed - in process]

Strong acute toxicity, severe hepatic damage, renal injury and abnormal serum electrolytes after intravenous administration of cadmium fluoride in rats.

J Occup Health. 2007 May;49(3):235-41

Authors: Adachi K, Dote T, Dote E, Mitsui G, Kono K

Cadmium fluoride (CdF) is commonly used as an insulator for ulta high speed mass telecommunications equipment, and there is a considerable risk that industrial workers will inhale CdF particles. Despite the possibility that acute exposure can cause harmful systemic effects, there are no studies to date that address the health consequences of acute CdF exposure. This study therefore aimed to determine the acute lethal dose of CdF and its effects on various target organs, including the liver and kidney. We also determined the effect of CdF on serum electrolytes and acid-base balance. The effective lethal dose was determined and dose-response study was conducted after intravenous administration of CdF in rats. The 24 h LD(50) of CdF was determined to be 3.29 mg/kg. The dose-response study used doses of 1.34, 2.67, 4.01 mg/kg CdF. Saline or sodium fluoride solution were used for controles. Severe hepatocellular injury was induced at doses greater than 2.67 mg/kg, as demonstrated by AST and ALT activities greater than 1,500 IU/l in rats injected with a dose of 4.01 mg/kg. Acute renal failure was induced at doses greater than 2.67 mg/kg. Decreased serum Ca, increased serum K and metabolic acidosis were induced at a dose of 4.01 mg/kg. Decreased serum Ca was caused by exposure to ionized F. CdF has the strongest lethal and hepatic toxicity among all Cd containing compounds.

PMID: 17575404 [PubMed - indexed for MEDLINE]

A 43 kD protein isolated from the herb Cajanus indicus L attenuates sodium fluoride-induced hepatic and renal disorders in vivo.

J Biochem Mol Biol. 2007 May 31;40(3):382-95

Authors: Manna P, Sinha M, Sil PC

The herb, Cajanus indicus L, is well known for its hepatoprotective action. A 43 kD protein has been isolated, purified and partially sequenced from the leaves of this herb. A number of in vivo and in vitro studies carried out in our laboratory suggest that this protein might be a major component responsible for the hepatoprotective action of the herb. Our successive studies have been designed to evaluate the potential efficacy of this protein in protecting the hepatic as well as renal tissues from the sodium fluoride (NaF) induced oxidative stress. The experimental groups of mice were exposed to NaF at a dose of 600 ppm through drinking water for one week. This exposure significantly altered the activities of the antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and the cellular metabolites such as reduced glutathione (GSH), oxidized glutathione (GSSG), total thiols, lipid peroxidation end products in liver and kidney compared to the normal mice. Intraperitoneal administration of the protein at a dose of 2 mg/kg body weight for seven days followed by NaF treatment (600 ppm for next seven days) normalized the activities of the hepato-renal antioxidant enzymes, the level of cellular metabolites and lipid peroxidation end products. Post treatment with the protein for four days showed that it could help recovering the damages after NaF administration. Time-course study suggests that the protein could stimulate the recovery of both the organs faster than natural process. Effects of a known antioxidant, vitamin E, and a non-relevant protein, bovine serum albumin (BSA) have been included in the study to validate the experimental data. Combining all, result suggests that NaF could induce severe oxidative stress both in the liver and kidney tissues in mice and the protein possessed the ability to attenuate that hepato-renal toxic effect of NaF probably via its antioxidant activity.

PMID: 17562290 [PubMed - indexed for MEDLINE]

Analysis of mitotic phosphorylation of borealin.

BMC Cell Biol. 2007;8:5

Authors: Kaur H, Stiff AC, Date DA, Taylor WR

BACKGROUND: The main role of the chromosomal passenger complex is to ensure that Aurora B kinase is properly localized and activated before and during mitosis. Borealin, a member of the chromosomal passenger complex, shows increased expression during G2/M phases and is involved in targeting the complex to the centromere and the spindle midzone, where it ensures proper chromosome segregation and cytokinesis. Borealin has a consensus CDK1 phosphorylation site, threonine 106 and can be phosphorylated by Aurora B Kinase at serine 165 in vitro. RESULTS: Here, we show that Borealin is phosphorylated during mitosis in human cells. Dephosphorylation of Borealin occurs as cells exit mitosis. The phosphorylated form of Borealin is found in an INCENP-containing complex in mitosis. INCENP-containing complexes from cells in S phase are enriched in the phosphorylated form suggesting that phosphorylation may encourage entry of Borealin into the chromosomal passenger complex. Although Aurora B Kinase is found in complexes that contain Borealin, it is not required for the mitotic phosphorylation of Borealin. Mutation of T106 or S165 of Borealin to alanine does not alter the electrophoretic mobility shift of Borealin. Experiments with cyclohexamide and the phosphatase inhibitor sodium fluoride suggest that Borealin is phosphorylated by a protein kinase that can be active in interphase and mitosis and that the phosphorylation may be regulated by a short-lived phosphatase that is active in interphase but not mitosis. CONCLUSION: Borealin is phosphorylated during mitosis. Neither residue S165, T106 nor phosphorylation of Borealin by Aurora B Kinase is required to generate the mitotic, shifted form of Borealin. Suppression of phosphorylation during interphase is ensured by a labile protein, possibly a cell cycle regulated phosphatase.

PMID: 17241471 [PubMed - indexed for MEDLINE]

Effects of systemic fluoride and in vitro fluoride treatment on enamel crystals.

J Dent Res. 2006 Nov;85(11):1042-5

Authors: Chen H, Czajka-Jakubowska A, Spencer NJ, Mansfield JF, Robinson C, Clarkson BH

Systemically administered fluoride at a concentration of 75 ppm increases the surface roughness of developing enamel crystals in rats, which may be significant in advancing our understanding of the biological mechanism of fluorosis. Thus, the aim of this study was to investigate whether the increased surface roughness may be a result of surface restructuring by the direct action of fluoride at the crystal surface. We examined the fluoride dose-dependent roughening of enamel crystal surfaces in vivo, in the rat, and whether this roughening could be mimicked by the in vitro treatment of rat enamel crystals with neutral pH fluoride solutions. Our results showed that enamel crystal surface roughness increased after treatment with increasing fluoride ion concentrations, whether applied in vitro or administered systemically. This suggests a mechanism, alongside others, for the increased surface roughness of crystals in fluorotic enamel.

PMID: 17062747 [PubMed - indexed for MEDLINE]

Deposition of fluoride on enamel surfaces released from varnishes is limited to vicinity of fluoridation site.

Clin Oral Investig. 2007 Mar;11(1):83-8

Authors: Attin T, Lennon AM, Yakin M, Becker K, Buchalla W, Attin R, Wiegand A

The aim of the in-situ study was to determine fluoride uptake in non-fluoridated, demineralized enamel after application of fluoride varnishes on enamel samples located at various distances from the non-fluoridated samples. All enamel samples used were demineralized with acidic hydroxyethylcellulose before the experiment. Intra-oral appliances were worn by ten volunteers in three series: (1, Mirafluorid, 0.15% F; 2, Duraphat, 2.3% F and 3, unfluoridated controls) of 6 days each. Each two enamel samples were prepared from 30 bovine incisors. One sample was used for the determination of baseline fluoride content (BFC); the other was treated according to the respective series and fixed in the intra-oral appliance for 6 days. Additionally, from 120 incisors, each four enamel samples were prepared (one for BFC). Three samples (a-c) were placed into each appliance at different sites: (a) directly neighboured to the fluoridated specimen (=next), (b) at 1-cm distance (=1 cm) and (c) in the opposite buccal aspect of the appliance (=opposite). At these sites, new unfluoridated samples were placed at days 1, 3 and 5, which were left in place for 1 day. The volunteers brushed their teeth and the samples with fluoridated toothpaste twice per day. Both the KOH-soluble and structurally bound fluoride were determined in all samples to determine fluoride uptake and were statistically analyzed. One day, after fluoridation with Duraphat, KOH-soluble fluoride uptake in specimen a (=next) was significantly higher compared to the corresponding samples of both the control and Mirafluorid series, which in turn were not significantly different from each other. At all other sites and time points, fluoride uptake in the enamel samples were not different from controls for both fluoride varnishes. Within the first day after application, intra-oral-fluoride release from the tested fluoride varnish Duraphat leads to KOH-soluble fluoride uptake only in enamel samples located in close vicinity to the fluoridation site.

PMID: 17043869 [PubMed - indexed for MEDLINE]

Ca, Pi, and F in the fluid of biofilm formed under sucrose.

J Dent Res. 2006 Sep;85(9):834-8

Authors: Tenuta LM, Del Bel Cury AA, Bortolin MC, Vogel GL, Cury JA

Calcium (Ca), inorganic phosphorus (P(i)), and fluoride (F) concentrations are low in the whole plaque biofilm formed under exposure to sucrose. It was hypothesized that this would be reflected in the biofilm fluid, where these low values should greatly influence the de/remineralization process. Dental biofilms were formed in situ over enamel blocks mounted in palatal appliances and exposed 8 times/day to distilled water, glucose+fructose, or sucrose solutions for 14 days. While Ca, P(i), and F concentrations in the whole biofilms were significantly lower in the glucose+fructose and sucrose groups, no effect on biofilm fluid was observed, even after a cariogenic challenge. An increase in whole biofilm mineral ions was observed 24 hrs after the carbohydrate treatments were suspended, but this effect was also not observed in the fluid. These results suggest that there is a homeostatic mechanism that maintains biofilm fluid mineral ion concentration, regardless of its total concentration in the whole biofilm.

PMID: 16931867 [PubMed - indexed for MEDLINE]

Remineralization of enamel caries can decrease optical reflectivity.

J Dent Res. 2006 Sep;85(9):804-8

Authors: Jones RS, Fried D

The remineralization of enamel caries can lead to distinct optical changes within a lesion. We hypothesized that the restoration of mineral volume would result in a measurable decrease in the depth-resolved reflectivity of polarized light from the lesion. To test this hypothesis, we measured optical changes in artificial caries undergoing remineralization as a function of depth, using Polarization-sensitive Optical Coherence Tomography (PS-OCT). Lesions were imaged non-destructively before and after exposure to a remineralization regimen. After imaging, microradiographs of histological thin sections indicated that the significant reflectivity reduction measured by PS-OCT accurately represented the increase in mineral content within a larger repaired surface zone. Mineral volume changes arising from remineralization can be measured on the basis of the optical reflectivity of the lesion.

PMID: 16931861 [PubMed - indexed for MEDLINE]

Lack of DNA damage induced by fluoride on mouse lymphoma and human fibroblast cells by single cell gel (comet) assay.

Braz Dent J. 2006;17(2):91-4

Authors: Ribeiro DA, Alves de Lima PL, Marques ME, Salvadori DM

Fluoride has widely been used in Dentistry because it is a specific and effective caries prophylactic agent. However, excess fluoride may represent a hazard to human health, especially by causing injury on genetic apparatus. Genotoxicity tests constitute an important part of cancer research for risk assessment of potential carcinogens. In this study, the potential DNA damage associated with exposure to fluoride was assessed by the single cell gel (comet) assay in vitro. Mouse lymphoma and human fibroblast cells were exposed to sodium fluoride (NaF) at final concentration ranging from 7 to 100 microg/mL for 3 h at 37 degrees C. The results pointed out that NaF in all tested concentrations did not contribute to DNA damage as depicted by the mean tail moment and tail intensity for both cellular types assessed. These findings are clinically important because they represent a valuable contribution for evaluation of the potential health risk associated with exposure to agents usually used in dental practice.

PMID: 16924333 [PubMed - indexed for MEDLINE]

Efficacy of a herbal toothpaste on patients with established gingivitis--a randomized controlled trial.

Braz Oral Res. 2006 Apr-Jun;20(2):172-7

Authors: Ozaki F, Pannuti CM, Imbronito AV, Pessotti W, Saraiva L, de Freitas NM, Ferrari G, Cabral VN

The aim of this randomised, double blind controlled trial was to verify the efficacy of a herbal dentifrice on the reduction of plaque and gingivitis. Forty eight volunteers with established gingivitis were randomly assigned to either a test group (herbal dentifrice) or positive control group (dentifrice with triclosan and fluoride). The dentifrices were distributed in plain white tubes by an independent pharmacy, which revealed the contents of each tube only after the experimental period. Plaque and gingivitis assessments were carried out on baseline and after 28 days of product use. All examinations were conducted by the same calibrated investigator. Subjects were instructed to brush their teeth three times daily using their assigned dentifrice for 28 days. There was a significant reduction in plaque levels in both the test and control groups. However, there was no significant difference between the groups. A significant reduction in gingivitis was observed in both groups, although there was no significant difference between them. No adverse reactions were reported. The authors concluded that both dentifrices were effective in reducing plaque and gingivitis in subjects with established gingivitis.

PMID: 16878213 [PubMed - indexed for MEDLINE]

Penetration of fluids into periodontal pockets using a powered toothbrush/irrigator device.

J Contemp Dent Pract. 2006 Jul 1;7(3):30-9

Authors: Brackett MG, Drisko CL, Thompson AL, Waller JL, Marshall DL, Schuster GS

This study was a single-blind, randomized, controlled clinical trial. The researchers evaluated a powered brush/irrigating device (HydraBrush Oral Health System; OHS) for its safety and ability to deliver a solution to the bottom of 5-6 mm pockets, compared to rinsing alone with a solution following brushing with a powered toothbrush (Sonicare Elite 7800; SE). An evaluation technique to measure the quantity and quality of solution able to enter the pocket was also introduced in this project. METHODS: Subjects were randomized in one of two-groups: brush plus simultaneous irrigation (OHS) versus brush plus rinsing (SE). Subjects used their devices at home for two weeks. At the measurement visit, subjects used the OHS to irrigate and brush simultaneously for 1 minute (30 seconds per each side of the mouth) with a 0.01% erythrosine disclosing solution in 10 oz of distilled water. Control subjects brushed for 2 minutes with a SE followed by a 1 minute rinse with an identical disclosing solution. A blinded evaluator collected six samples of approximately of 1 microL of sucular fluid from six 5-6 mm evaluation sites. This was accomplished by inserting a microcapillary tip with a 20 microL micropipette in the sulcus. Two-group repeated measures ANOVA was used to examine differences in two measures of the disclosing solution between OHS and SE subjects; the spectrometer reading of the disclosing solutions, and by visual inspection of the samples (positive/negative) to determine the presence or absence of solution in the samples. Subjects' diaries were collected. Bleeding and discomfort during the evaluation period was reported. RESULTS: Visually, OHS had a significantly greater proportion of solution taken from the base of 5-6 mm sites than the SE (p=0.0001). However, there was no statistical difference between the two groups (p=.1359) in the spectrophotometer readings. CONCLUSION: The experimental device is more efficient in delivering a solution to the base of 5-6 mm pockets than rinsing following use of a control powered toothbrush. Both devices have demonstrated they are safe and well accepted by patients. The technique developed provides a useful method for quantitative and qualitative studies of solutions from the base of periodontal pockets.

PMID: 16820805 [PubMed - indexed for MEDLINE]

A 24-hour dental plaque prevention study with a stannous fluoride dentifrice containing hexametaphosphate.

J Contemp Dent Pract. 2006 Jul 1;7(3):1-11

Authors: White DJ, Kozak KM, Gibb R, Dunavent J, Klukowska M, Sagel PA

Recently, a novel antibacterial fluoride dentifrice containing stannous fluoride and sodium hexametaphosphate (CrestPRO-HEALTH) was introduced. A digital plaque image analysis (DPIA) technique was used to quantify in situ plaque formation in a population carrying out a phased intervention protocol that included: (1) an initial treatment regimen including toothbrushing with standard sodium fluoride dentifrice in conventional bid brushing, (2) a second treatment regimen where a modified hygiene regimen was applied using standard sodium fluoride dentifrice including a period of 24 hours of non-brushing, and (3) a third treatment regimen where the 24-hour non-brushing regimen was continued using the antimicrobial stannous fluoride/sodium hexametaphosphate dentifrice. The quantitative evaluation of plaque formation was assessed in morning measurements following either standard evening hygiene (treatment period 1) or 24 hours since brushing (treatment periods 2 and 3). Post-brushing plaque measurements were also taken in each treatment regimen. Sixteen subjects completed all three treatment regimens with no side effects or oral complaints. Morning plaque coverage in treatment period 1 was 13.3%. Plaque coverage significantly increased in treatment period 2 when pre-bedtime brushing was discontinued, with 24-hour growth covering 18.4% of the dentition. Intervention of the antimicrobial stannous fluoride/hexametaphosphate dentifrice in treatment period 3 provided significant inhibition of plaque regrowth over 24 hours (15.2% coverage, a 17% reduction vs. sodium fluoride dentifrice control). These results support the strong retention and lasting antimicrobial efficacy of high stabilized stannous fluoride/sodium hexametaphosphate dentifrices.

PMID: 16820802 [PubMed - indexed for MEDLINE]

Treating cervical dentin hypersensitivity with fluoride varnish: a randomized clinical study.

J Am Dent Assoc. 2006 Jul;137(7):1013-20; quiz 1029

Authors: Ritter AV, de L Dias W, Miguez P, Caplan DJ, Swift EJ

BACKGROUND: This subject-blind randomized clinical trial tested the efficacy of a new 5 percent sodium fluoride varnish (AllSolutions Fluoride Varnish, Dentsply Professional, York, Pa.) for treatment of cervical dentin hypersensitivity. The authors also compared the test varnish with a control fluoride varnish (Duraphat, Colgate Oral Pharmaceuticals, New York City). METHODS: The study involved application of the test or control varnish to 19 subjects (59 teeth) with tooth sensitivity. The authors applied each product once to each tooth, following manufacturers' instructions. They used a visual analog scale (VAS) to assess subjects' responses to compressed air and ice stimuli at six weeks before baseline, at baseline and at two, eight and 24 weeks after treatment. RESULTS: Mean VAS scores for teeth receiving the test varnish dropped from 34.9 (air) and 68.0 (ice) at baseline to 26.3 (air) and 54.7 (ice) at two weeks after treatment. Mean scores at 24 weeks were 20.6 (air) and 34.8 (ice), representing statistically significant differences from baseline values. For the control varnish, mean VAS scores dropped from 36.9 (air) and 64.2 (ice) at baseline to 32.9 (air) and 47.2 (ice) at two weeks, and to 20.8 (air) and 40.3 (ice) at 24 weeks. The authors analyzed the data for statistical significance, accounting for clustering of teeth within subjects. CONCLUSION AND CLINICAL IMPLICATIONS: The test varnish was effective in reducing cervical dentin hypersensitivity. However, the efficacy was not significantly different from that of the control varnish.

PMID: 16803829 [PubMed - indexed for MEDLINE]

In situ mineral loss inhibition by CO2 laser and fluoride.

J Dent Res. 2006 Jul;85(7):617-21

Authors: Rodrigues LK, Nobre Dos Santos M, Featherstone JD

Laser and fluoride treatments have been shown to inhibit enamel demineralization in the laboratory. However, the intra-oral effects of this association have not been tested. This study assessed in situ the effect of a Transversely Excited Atmospheric CO2 laser (lambda = 9.6 mum) and the use of pressure fluoridated dentifrice on enamel demineralization. During two 14-day phases, 17 volunteers wore palatal appliances containing human enamel slabs assigned to treatment groups, as follows: (1) non-fluoride dentifrice, (2) CO2 laser irradiation plus non-fluoride dentifrice, (3) fluoride dentifrice, and (4) CO2 laser irradiation plus fluoride dentifrice. A 20% sucrose solution was dripped onto the slabs 8 times per day. The specimens treated with laser and/or fluoridated dentifrice presented a significantly lower mineral loss when compared with those from the non-fluoride dentifrice group. The results suggested that CO2 laser treatment of enamel inhibits demineralization in the human mouth, being more effective when associated with fluoride.

PMID: 16798861 [PubMed - indexed for MEDLINE]

Effect of fluoride toothpastes on enamel demineralization.

BMC Oral Health. 2006;6:8

Authors: Arnold WH, Dorow A, Langenhorst S, Gintner Z, B&#xE1;nóczy J, Gaengler P

BACKGROUND: It was the aim of this study to investigate the effect of four different toothpastes with differing fluoride compounds on enamel remineralization. METHODS: A 3 x 3 mm window on the enamel surface of 90 human premolars was demineralized in a hydroxyethylcellulose solution at pH 4.8. The teeth were divided into 6 groups and the lower half of the window was covered with varnish serving as control. The teeth were immersed in a toothpaste slurry containing: placebo tooth paste (group 1); remineralization solution (group 2); Elmex Anticaries (group 3); Elmex Sensitive (group 4); Blend-a-med Complete (group 5) and Colgate GRF (group 6). Ten teeth of each group were used for the determination of the F- content in the superficial enamel layer and acid solubility of enamel expressed in soluble phosphorus. Of 6 teeth of each group serial sections were cut and investigated with polarization light microscopy (PLM) and quantitative energy dispersive X-ray analysis (EDX). RESULTS: The PLM results showed an increased remineralization of the lesion body in the Elmex Anticaries, Elmex Sensitive and Colgate GRF group but not in the Blend-a-med group. A statistically significant higher Ca content was found in the Elmex Anticaries group. The fluoride content in the superficial enamel layer was significantly increased in both Elmex groups and the Blend-a-med group. Phosphorus solubility was significantly decreased in both Elmex groups and the Blend-a-med group. CONCLUSION: It can be concluded that amine fluoride compounds in toothpastes result in a clearly marked remineralization of caries like enamel lesions followed by sodium fluoride and sodium monofluorophosphate formulations.

PMID: 16776820 [PubMed]

Efficacy and safety of a novel stabilized stannous fluoride and sodium hexametaphosphate dentifrice for dentinal hypersensitivity.

J Contemp Dent Pract. 2006 May 1;7(2):1-8

Authors: Schiff T, He T, Sagel L, Baker R

PURPOSE: Dentinal hypersensitivity is a common complaint among dental patients. Recently, a novel 0.454% stabilized stannous fluoride dentifrice containing sodium hexametaphosphate (SHMP) was introduced that offers a desensitizing benefit. This trial was conducted to assess the desensitizing efficacy of this new dentifrice relative to a sodium fluoride control dentifrice. METHODS AND MATERIAL: This was a double-blind, parallel-group, randomized clinical trial conducted according to the American Dental Association (ADA) Guidelines for the Acceptance of Products for the Treatment of Dentinal Hypersensitivity. Ninety subjects who met the entrance criteria were stratified based on age, gender, and baseline sensitivity scores and randomly assigned to either the stabilized stannous fluoride + SHMP dentifrice (Crest Pro-Health) or the sodium fluoride control dentifrice. Subjects were instructed to brush twice daily for eight weeks. Efficacy assessments were made, including tactile (Yeaple probe) and thermal (Schiff Air Index) sensitivity, and an oral soft tissue examination was conducted at baseline, week four, and week eight. RESULTS: The mean sensitivity score based on the Schiff Air Index for the stannous fluoride + SHMP group was statistically significantly lower than that of the control group, at both weeks four and eight (P < .0001). At week eight, the stannous fluoride + SHMP dentifrice group had an adjusted mean 44% lower than that of the control group. The mean tactile sensitivity score for the stannous fluoride + SHMP group was statistically significantly higher, indicating a reduction in sensitivity, than that of the control group, at both weeks four and eight (P < .0001). At week eight, the stannous fluoride + SHMP dentifrice group had a mean desensitizing improvement of 71% greater than the control. CONCLUSION: The stabilized stannous fluoride + SHMP dentifrice provided statistically significant reductions in dentinal hypersensitivity at four and eight weeks compared to the sodium fluoride control dentifrice.

PMID: 16685289 [PubMed - indexed for MEDLINE]

The combined occluding effects of fluoride-containing dentin desensitizer and Nd-Yag laser irradiation on human dentinal tubules: an in vitro study.

Kaohsiung J Med Sci. 2006 Jan;22(1):24-9

Authors: Hsu PJ, Chen JH, Chuang FH, Roan RT

The purpose of the present study was to evaluate the combined occluding effects of fluoride-containing dentin desensitizer and neodymium:yttrium aluminum garnet (Nd-YAG) laser irradiation on human dentinal tubules. All six of the groups of dentin samples (A-F) included in this study received applications of fluoride-containing dentin desensitizer. Groups B, D, and F also received Nd-YAG laser irradiation. Groups A and B served as controls, to allow observations of the occluding effects on the dentinal tubules before and after Nd-YAG laser irradiation. Groups C and D were treated with 0.5 M vitamin C solution, whereas groups E and F underwent brushing with an electric toothbrush. Scanning electron microscopy (SEM) revealed that the fluoridated dentinal tubule-occluding agent (FDTOA) formed a fine crystalline deposit on the dentin surface. After soaking in 0.5 M vitamin C solution for 3 hours, the crystalline deposit of the FDTOA was completely dissolved. Furthermore, brushing of the teeth 3,600 times removed most of the occluding agent. When the application of FDTOA was combined with Nd-YAG laser irradiation, the dentin melted and then recrystallized. The occluding agent was thus 'burned into' the dentinal tubules, and could neither be dissolved by vitamin C solution nor removed by brushing. Therefore, we concluded that the FDTOA combined with Nd-YAG laser irradiation burns the occluding agent into the dentinal tubules, thereby resisting the effects of an acidic diet and brushing, and increasing the duration of the desensitizing effect.

PMID: 16570565 [PubMed - indexed for MEDLINE]

Characterization of the Highly Autolytic Lactococcus lactis subsp. cremoris Strains CO and 2250.

Appl Environ Microbiol. 1997 Oct;63(10):3757-3763

Authors: Riepe HR, Pillidge CJ, Gopal PK, McKay LL

Two highly autolytic Lactococcus lactis subsp. cremoris strains (CO and 2250) were selected and analyzed for their autolytic properties. Both strains showed maximum lysis when grown in M17 broth containing a limiting concentration of glucose (0.4 to 0.5%) as the carbohydrate source. Lysis did not vary greatly with pH or temperature but was reduced when strains were grown on lactose or galactose. Growth in M17 containing excess glucose (1%) prevented autolysis, although rapid lysis of L. lactis subsp. cremoris CO did occur in the presence of 1% glucose if sodium fluoride (an inhibitor of glycolysis) was added to the medium. Maximum cell lysis in a buffer system was observed early in the stationary phase, and for CO, two pH optima were observed for log-phase and stationary-phase cells (6.5 and 8.5, respectively). Autolysins were extracted from the cell wall fraction of each strain by using either 4% sodium dodecyl sulfate (SDS), 6 M guanidine hydrochloride, or 4 M lithium chloride, and their activities were analyzed by renaturing SDS-polyacrylamide gel electrophoresis on gels containing Micrococcus luteus or L. lactis subsp. cremoris CO cells as the substrate. More than one lytic band was observed on each substrate, with the major band having an apparent molecular mass of 48 kDa for CO. Each lytic band was present throughout growth and lysis. These results suggest that at least two different autolytic enzymes are present in the autolytic L. lactis subsp. cremoris strains. The presence of the lactococcal cell wall hydrolase gene, acmA (G. Buist, J. Kok, K. J. Leenhouts, M. Dabrowska, G. Venema, and A. J. Haandrikman, J. Bacteriol. 177:1554-1563, 1995), in strains 2250 and CO was confirmed by Southern hybridization. Analysis of an acmA deletion mutant of 2250 confirmed that the gene was involved in cell separation and had a role in cell lysis.

PMID: 16535702 [PubMed - as supplied by publisher]

DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes.

World J Gastroenterol. 2006 Feb 21;12(7):1144-8

Authors: He LF, Chen JG

AIM: To study the effect of fluoride on oxidative stress, DNA damage and apoptosis as well as cell cycle of rat oral mucosal cells and hepatocytes. METHODS: Ten male SD rats weighing 80-120 g were randomly divided into control group and fluoride group, 5 animals each group. The animals in fluoride group had free access to deionized water containing 150 mg/L sodium fluoride (NaF). The animals in control group were given distilled water. Four weeks later, the animals were killed. Reactive oxygen species (ROS) in oral mucosa and liver were measured by Fenton reaction, lipid peroxidation product, malondialdehyde (MDA), was detected by thiobarbituric acid (TBA) reaction, reduced glutathione (GSH) was assayed by dithionitrobenzoic acid (DTNB) reaction. DNA damage in oral mucosal cells and hepatocytes was determined by single cell gel (SCG) electrophoresis or comet assay. Apoptosis and cell cycle in oral mucosal cells and hepatocytes were detected by flow cytometry. RESULTS: The contents of ROS and MDA in oral mucosa and liver tissue of fluoride group were significantly higher than those of control group (P < 0.01), but the level of GSH was markedly decreased (P < 0.01). The contents of ROS, MDA and GSH were (134.73 +/- 12.63) U/mg protein, (1.48 +/- 0.13) mmol/mg protein and (76.38 +/- 6.71) mmol/mg protein in oral mucosa respectively, and (143.45 +/- 11.76) U/mg protein, (1.44 +/- 0.12) mmol/mg protein and (78.83 +/- 7.72) mmol/mg protein in liver tissue respectively. The DNA damage rate in fluoride group was 50.20% in oral mucosal cells and 44.80% in hepatocytes, higher than those in the control group (P < 0.01). The apoptosis rate in oral mucosal cells was (13.63 +/- 1.81) % in fluoride group, and (12.76 +/- 1.67)% in hepatocytes, higher than those in control group. Excess fluoride could differently lower the number of oral mucosal cells and hepatocytes at G0/G1 and S G2/M phases (P < 0.05). CONCLUSION: Excess fluoride can induce oxidative stress and DNA damage and lead to apoptosis and cell cycle change in rat oral mucosal cells and hepatocytes.

PMID: 16534862 [PubMed - indexed for MEDLINE]

Transient decrease of light-harvesting complex II phosphorylation level by hypoosmotic shock in dark-adapted Dunaliella salina.

Acta Biochim Biophys Sin (Shanghai). 2006 Feb;38(2):104-9

Authors: Liu XD, Hu FH, Shen YG

This study investigated the regulation of major light harvesting chlorophyll a/b protein (LHCII) phosphorylation by hypoosmotic shock in dark-adapted Dunaliella salina cells. When the external NaCl concentration decreased in darkness, D. salina LHCII phosphorylation levels transiently dropped within 20 min and then restored gradually to basal levels. The transient decrease in LHCII phosphorylation levels was insensitive to NaF, a phosphatase inhibitor. Inhibition of intracellular ATP production by addition of an uncoupler or an ATP synthase inhibitor increased LHCII phosphorylation levels in D. salina cells exposed to hypoosmotic shock. Taken together, these results indicate that hypoosmotic shock inhibits the LHCII phosphorylation process. The related mechanism and physiological significance are discussed.

PMID: 16474901 [PubMed - indexed for MEDLINE]

Fluoride varnish efficacy in preventing early childhood caries.

J Dent Res. 2006 Feb;85(2):172-6

Authors: Weintraub JA, Ramos-Gomez F, Jue B, Shain S, Hoover CI, Featherstone JD, Gansky SA

To determine the efficacy of fluoride varnish (5% NaF, Duraphat, Colgate) added to caregiver counseling to prevent early childhood caries, we conducted a two-year randomized, dental-examiner-masked clinical trial. Initially, 376 caries-free children, from low-income Chinese or Hispanic San Francisco families, were enrolled (mean age +/- standard deviation, 1.8 +/- 0.6 yrs). All families received counseling, and children were randomized to the following groups: no fluoride varnish, fluoride varnish once/year, or fluoride varnish twice/year. An unexpected protocol deviation resulted in some children receiving less active fluoride varnish than assigned. Intent-to-treat analyses showed a fluoride varnish protective effect in caries incidence, p < 0.01. Analyzing the number of actual, active fluoride varnish applications received resulted in a dose-response effect, p < 0.01. Caries incidence was higher for 'counseling only' vs. 'counseling + fluoride varnish assigned once/year' (OR = 2.20, 95% CI 1.19-4.08) and 'twice/year' (OR = 3.77, 95% CI 1.88-7.58). No related adverse events were reported. Fluoride varnish added to caregiver counseling is efficacious in reducing early childhood caries incidence.

PMID: 16434737 [PubMed - indexed for MEDLINE]

Galvanic corrosion between orthodontic wires and brackets in fluoride mouthwashes.

Eur J Orthod. 2006 Jun;28(3):298-304

Authors: Schiff N, Boinet M, Morgon L, Lissac M, Dalard F, Grosgogeat B

The aim of this investigation was to determine the influence of fluoride in certain mouthwashes on the risk of corrosion through galvanic coupling of orthodontic wires and brackets. Two titanium alloy wires, nickel-titanium (NiTi) and copper-nickel-titanium (CuNiTi), and the three most commonly used brackets, titanium (Ti), iron-chromium-nickel (FeCrNi) and cobalt-chromium (CoCr), were tested in a reference solution of Fusayama-Meyer artificial saliva and in two commercially available fluoride (250 ppm) mouthwashes, Elmex and Meridol. Corrosion resistance was assessed by inductively coupled plasma-atomic emission spectrometry (ICP-MS), analysis of released metal ions, and a scanning electron microscope (SEM) study of the metal surfaces after immersion of different wire-bracket pairs in the test solutions. The study was completed by an electrochemical analysis. Meridol mouthwash, which contains stannous fluoride, was the solution in which the NiTi wires coupled with the different brackets showed the highest corrosion risk, while in Elmex mouthwash, which contains sodium fluoride, the CuNiTi wires presented the highest corrosion risk. Such corrosion has two consequences: deterioration in mechanical performance of the wire-bracket system, which would negatively affect the final aesthetic result, and the risk of local allergic reactions caused by released Ni ions. The results suggest that mouthwashes should be prescribed according to the orthodontic materials used. A new type of mouthwash for use during orthodontic therapy could be an interesting development in this field.

PMID: 16428255 [PubMed - indexed for MEDLINE]

Mechanism of fluoride-induced MAP kinase activation in pulmonary artery endothelial cells.

Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1139-45

Authors: Bogatcheva NV, Wang P, Birukova AA, Verin AD, Garcia JG

In this study, we demonstrate that challenge of endothelial cells (EC) with NaF, a recognized G protein activator and protein phosphatase inhibitor, leads to a significant Erk activation, with increased phosphorylation of the well-known Erk substrate caldesmon. Inhibition of the Erk MAPK, MEK, by U0126 produces a marked decrease in NaF-induced caldesmon phosphorylation. NaF transiently increases the activity of the MEK kinase known as Raf-1 (approximately 3- to 4-fold increase over basal level), followed by a sustained Raf-1 inhibition (approximately 3- to 4-fold decrease). Selective Raf-1 inhibitors (ZM-336372 and Raf-1 inhibitor 1) significantly attenuate NaF-induced Erk and caldesmon phosphorylation. Because we have previously shown that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) participates in Erk activation in thrombin-challenged cells, we next explored if CaMKII is involved in NaF-induced EC responses. We found that in NaF-treated EC, CaMKII activity increases in a time-dependent manner with maximal activity at 10 min (approximately 4-fold increase over a basal level). Pretreatment with KN93, a specific CaMKII inhibitor, attenuates NaF-induced barrier dysfunction and Erk phosphorylation. The Rho inhibitor C3 exotoxin completely abolishes NaF-induced CaMKII activation. Collectively, these data suggest that sequential activation of Raf-1, MEK, and Erk is modulated by Rho-dependent CaMKII activation and represents important NaF-induced signaling response. Caldesmon phosphorylation occurring by an Erk-dependent mechanism in NaF-treated pulmonary EC may represent a link between NaF stimulation and contractile responses of endothelium.

PMID: 16414982 [PubMed - indexed for MEDLINE]

Phosphorylation of serine 526 is required for MEKK3 activity, and association with 14-3-3 blocks dephosphorylation.

J Biol Chem. 2006 Mar 10;281(10):6236-45

Authors: Fritz A, Brayer KJ, McCormick N, Adams DG, Wadzinski BE, Vaillancourt RR

MAPK/ERK kinase kinase 3 (MEKK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that functions upstream of the MAP kinases and IkappaB kinase. Phosphorylation is believed to be a critical component for MEKK3-dependent signal transduction, but little is known about the phosphorylation sites of this MAP3K. To address this question, point mutations were introduced in the activation loop (T-loop), substituting alanine for serine or threonine, and the mutants were transfected into HEK293 Epstein-Barr virus nuclear antigen cells. MEKK3-dependent activation of an NF-kappaB reporter gene as well as ERK, JNK, and p38 MAP kinases correlated with a requirement for serine at position 526. Constitutively active mutants of MEKK3, consisting of S526D and S526E, were capable of activating a NF-kappaB luciferase reporter gene as well as ERK and MEK, suggesting that a negative charge at Ser526 was necessary for MEKK3 activity and implicating Ser526 as a phosphorylation site. An antibody was developed that specifically recognized phospho-Ser526 of MEKK3 but did not recognize the S526A point mutant. The catalytically inactive (K391M) mutant of MEKK3 was not phosphorylated at Ser526, indicating that phosphorylation of Ser526 occurs via autophosphorylation. Endogenous MEKK3 was phosphorylated on Ser526 in response to osmotic stress. In addition, phosphorylation of Ser526 was required for MKK6 phosphorylation in vitro, whereas dephosphorylation of Ser526 was mediated by protein phosphatase 2A and sensitive to okadaic acid and sodium fluoride. Finally, the association between MEKK3 and 14-3-3 was dependent on Ser526 and prevented dephosphorylation of Ser526. In summary, Ser526 of MEKK3 is an autophosphorylation site within the T-loop that is regulated by PP2A and 14-3-3 proteins.

PMID: 16407301 [PubMed - indexed for MEDLINE]

Blood lead concentrations in children and method of water fluoridation in the United States, 1988-1994.

Environ Health Perspect. 2006 Jan;114(1):130-4

Authors: Macek MD, Matte TD, Sinks T, Malvitz DM

Some have hypothesized that community water containing sodium silicofluoride and hydrofluosilicic acid may increase blood lead (PbB) concentrations in children by leaching of lead from water conduits and by increasing absorption of lead from water. Our analysis aimed to evaluate the relation between water fluoridation method and PbB concentrations in children. We used PbB concentration data (n=9,477) from the Third National Health and Nutrition Examination Survey (1988-1994) for children 1-16 years of age, merged with water fluoridation data from the 1992 Fluoridation Census. The main outcome measure was geometric mean PbB concentration, and covariates included age, sex, race/ethnicity, poverty status, urbanicity, and length of time living in residence. Geometric mean PbB concentrations for each water fluoridation method were 2.40 microg/dL (sodium silicofluoride), 2.34 microg/dL (hydrofluosilicic acid), 1.78 microg/dL (sodium fluoride), 2.24 microg/dL (natural fluoride and no fluoride), and 2.14 microg/dL (unknown/mixed status). In multiple linear and logistic regression, there was a statistical interaction between water fluoridation method and year in which dwelling was built. Controlling for covariates, water fluoridation method was significant only in the models that included dwellings built before 1946 and dwellings of unknown age. Across stratum-specific models for dwellings of known age, neither hydrofluosilicic acid nor sodium silicofluoride were associated with higher geometric mean PbB concentrations or prevalence values. Given these findings, our analyses, though not definitive, do not support concerns that silicofluorides in community water systems cause higher PbB concentrations in children. Current evidence does not provide a basis for changing water fluoridation practices, which have a clear public health benefit.

PMID: 16393670 [PubMed - indexed for MEDLINE]

Early biofilm formation and the effects of antimicrobial agents on orthodontic bonding materials in a parallel plate flow chamber.

Eur J Orthod. 2006 Feb;28(1):1-7

Authors: Chin MY, Busscher HJ, Evans R, Noar J, Pratten J

Decalcification is a commonly recognized complication of orthodontic treatment with fixed appliances. A technology, based on a parallel plate flow chamber, was developed to investigate early biofilm formation of a strain of Streptococcus sanguis on the surface of four orthodontic bonding materials: glass ionomer cement (Ketac Cem), resin-modified glass ionomer cement (Fuji Ortho LC), chemically-cured composite resin (Concise) and light-cured composite resin (Transbond XT). S. sanguis was used as it is one of the primary colonizers of dental hard surfaces. Artificial saliva was supplied as a source of nutrients for the biofilms. The effects of two commercially available mouthrinses (i.e. a fluoride containing rinse and chlorhexidine) were evaluated. Initial colonization of the bacterium was assessed after 6 hours of growth by the percentage surface coverage (PSC) of the biofilm on the disc surfaces. There were statistically significant differences in bacterial accumulation between different bonding materials (P < 0.05), Concise being the least colonized and Transbond XT being the most colonized by S. sanguis biofilms. All materials pre-treated with 0.05 per cent sodium fluoride mouthrinse showed more than 50 per cent reduction in biofilm formation. The 0.2 per cent chlorhexidine gluconate mouthrinse caused significant reduction of biofilm formation on all materials except Ketac Cem. This in vitro study showed that the use of a chemically-cured composite resin (Concise) reduced early S. sanguis biofilm formation. Also, fluoride had a greater effect in reducing the PSC by S. sanguis biofilms than chlorhexidine. Rinsing with 0.05 per cent sodium fluoride prior to placement of orthodontic appliances is effective in reducing early biofilm formation.

PMID: 16373451 [PubMed - indexed for MEDLINE]

Response of osteoblastic cells to titanium submitted to three different surface treatments.

Braz Oral Res. 2005 Jul-Sep;19(3):203-8

Authors: Santiago AS, Santos EA, Sader MS, Santiago MF, Soares Gde A

In the complex process of bone formation at the implant-tissue interface, surface properties are relevant factors modulating osteoblastic function. In this study, commercially pure titanium (cp Ti) samples were prepared with different surface characteristics using chemical attack with a sulfuric acid/hydrochloric acid based solution (treatment A); chemical attack plus anodic oxidation using phosphoric acid (treatment B); and chemical attack plus thermal oxidation followed by immersion in a sodium fluoride solution (treatment C). The samples were characterized by scanning electron microscopy (SEM), contact profilometry and contact angle. The biological performance of the prepared surfaces was evaluated using mice osteoblastic cell cultures for up to 21 days. Cells seeded on the different titanium samples showed similar behavior during cell attachment and spreading. However, cellular proliferation and differentiation were higher for samples submitted to treatments A and C (p < or = 0.05; n = 3), which were less rough and showed surface free energy with smaller polar components.

PMID: 16308609 [PubMed - indexed for MEDLINE]

Sealant and fluoride varnish in caries: a randomized trial.

J Dent Res. 2005 Dec;84(12):1138-43

Authors: Bravo M, Montero J, Bravo JJ, Baca P, Llodra JC

Little is known about the effect of discontinuation of sealant or fluoride varnish. The purpose of this study was to compare sealant with fluoride varnish in the prevention of occlusal caries in permanent first molars of children over a nine-year period: 4 yrs for program evaluation plus 5 yrs of discontinuation. A clinical trial was conducted on three groups of six- to eight-year-old schoolchildren: a control group (n = 45); a group (n = 37) in which sealant was applied and reapplied up to 36 mos; and a group (n = 38) in which fluoride varnish was applied and re-applied up to 42 mos. Percent caries reduction was studied in these initially healthy molars with complete occlusal eruption: 129 (control), 113 (sealant), and 129 (varnish) molars met inclusion criteria. Of these, 76.7%, 26.6%, and 55.8% had developed occlusal caries at 9 yrs, which implies caries reductions of 65.4% (SE = 8.5%) for sealants vs. control and 27.3% (SE = 10.2%) for varnish vs. control. Furthermore, the varnish program was not effective during the discontinuation period.

PMID: 16304443 [PubMed - indexed for MEDLINE]

A prospective, randomized clinical study on the effects of an amine fluoride/stannous fluoride toothpaste/mouthrinse on plaque, gingivitis and initial caries lesion development in orthodontic patients.

Eur J Orthod. 2006 Feb;28(1):8-12

Authors: &#xD8;gaard B, Alm AA, Larsson E, Adolfsson U

The aim of this study was to examine the effect of combined use of a toothpaste/mouthrinse containing amine fluoride/stannous fluoride (AmF/SnF2; meridol) on the development of white spot lesions, plaque, and gingivitis on maxillary anterior teeth in orthodontic patients. A prospective, randomized, double-blind study with 115 orthodontic patients (42 males and 73 females, average age 14.4 years, drop outs 18) was designed. Group A (50) brushed twice daily with an AmF/SnF2 toothpaste (1400 ppm F) and rinsed every evening with an AmF/SnF2 solution (250 ppm F). Group B (47) brushed twice daily with a sodium fluoride (NaF) toothpaste (1400 ppm F) and rinsed every evening with a NaF solution (250 ppm F). Visible plaque index (VPI), gingival bleeding index (GBI) and white spot lesion index (WSL) were recorded on the six maxillary anterior teeth at bonding and after debonding, and evaluated with t tests. In group A no significant differences between bonding and debonding were recorded for WSL (1.02 +/- 0.08 versus 1.05 +/- 0.13, P = 0.14), VPI (0.10 +/- 0.21 versus 0.12 +/- 0.21, P = 0.66) or GBI (0.13 +/- 0.21 versus 0.16 +/- 0.22, P = 0.47), whereas statistically significant differences were found in group B between bonding and debonding for WSL (1.00 +/- 0.02 versus 1.08 +/- 0.17, P = 0.01), VPI (0.06 +/- 0.13 versus 0.17 +/- 0.25, P = 0.01) and GBI (0.06 +/- 0.12 versus 0.16 +/- 0.21, P = 0.01). The increase in lesions on the upper anterior teeth was 4.3 per cent in group A and 7.2 per cent in group B. It was concluded that the combined use of an AmF/SnF2 toothpaste/mouthrinse had a slightly more inhibitory effect on white spot lesion development, plaque and gingivitis on maxillary anterior teeth during fixed orthodontic treatment compared with NaF.

PMID: 16230329 [PubMed - indexed for MEDLINE]

Possible link between glycolysis and apoptosis induced by sodium fluoride.

J Dent Res. 2005 Oct;84(10):919-23

Authors: Otsuki S, Morshed SR, Chowdhury SA, Takayama F, Satoh T, Hashimoto K, Sugiyama K, Amano O, Yasui T, Yokote Y, Akahane K, Sakagami H

Fluoride has been used to prevent caries in the dentition, but the possible underlying mechanisms of cytotoxicity induction by this compound are still unclear. Since fluoride is known as an inhibitor of glycolytic enzymes, we investigated the possible connection between NaF-induced apoptosis and glycolysis in human promyelocytic leukemia HL-60 cells. NaF-induced apoptotic cell death is characterized by caspase activation, internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, and production of apoptotic bodies. Higher activation of caspases-3 and -9, as compared with that of caspase-8, suggested the involvement of an extrinsic pathway. Utilization of glucose was nearly halted by NaF, whereas that of glutamine was rather enhanced. NaF enhanced the expression of Bad protein, but not that of Bcl-2 and Bax proteins, and reduced HIF-1alpha mRNA expression. Analysis of these data suggests a possible link between glycolysis and apoptosis.

PMID: 16183791 [PubMed - indexed for MEDLINE]

Use of vitamin C in delayed tooth replantation.

Braz Dent J. 2005;16(1):17-22

Authors: Panzarini SR, Perri de Carvalho AC, Poi WR, Sonoda CK

This study evaluated microscopically the effects of root surface treatment with three different solutions in delayed rat teeth replantation. Central incisors from 30 rats (Rattus norvegicus, albinus Wistar) were extracted and left on a bench for 6 h. The pulps were extirpated and root canals were irrigated with 1% sodium hypochlorite. After endodontic treatment, the root surfaces of all teeth were submitted to a 10-min treatment with 1% sodium hypochlorite, changed every 5 min. The teeth were then rinsed with saline for 10 min and assigned to 3 groups with ten specimens each. Groups I, II and III were treated, respectively, with 2% acidulated-phosphate sodium fluoride, vitamin C solution and effervescent vitamin C (2 g, Redoxon. After root surface treatment, the teeth were filled with calcium hydroxide and replanted. The animals were sacrificed after 10 and 60 days. Group I (fluoride) presented the largest areas of replacement resorption and ankylosis. Comparing both vitamin C groups, Group III (effervescent vitamin C) yielded better results, showing more areas of ankylosis and replacement resorption than areas of inflammatory resorption.

PMID: 16113928 [PubMed - indexed for MEDLINE]

Bayesian analysis of clustered interval-censored data.

J Dent Res. 2005 Sep;84(9):817-21

Authors: Wong MC, Lam KF, Lo EC

The recording of multiple interval-censored failure times is common in dental research. Modeling multilevel data has been a difficult task. This paper aims to use the Bayesian approach to analyze a set of multilevel clustered interval-censored data from a clinical study to investigate the effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting active dentin caries in Chinese pre-school children. The time to arrest dentin caries on a surface was measured. A three-level random-effects Weibull regression model was used. Analysis was performed with WinBUGS. Results revealed a strong positive correlation (0.596) among the caries lesions' arrest times on different surfaces from the same child. The software WinBUGS made the above complicated estimation simple. In conclusion, the annual application of silver diamine fluoride on caries lesions, and caries removal before the application, were found to shorten the arrest time.

PMID: 16109990 [PubMed - indexed for MEDLINE]

Effects of prolonged ambient storage of sodium fluoride/heparin specimens on plasma homocysteine.

Clin Chem. 2005 Aug;51(8):1564-5

Authors: Scheidhauer R, Guessregen B, Hohl A, Arndt T

PMID: 16040865 [PubMed - indexed for MEDLINE]

Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation.

J Biol Chem. 2005 Jun 17;280(24):23194-202

Authors: Kubota K, Lee DH, Tsuchiya M, Young CS, Everett ET, Martinez-Mier EA, Snead ML, Nguyen L, Urano F, Bartlett JD

The mechanism of how fluoride causes fluorosis remains unknown. Exposure to fluoride can inhibit protein synthesis, and this may also occur by agents that cause endoplasmic reticulum (ER) stress. When translated proteins fail to fold properly or become misfolded, ER stress response genes are induced that together comprise the unfolded protein response. Because ameloblasts are responsible for dental enamel formation, we used an ameloblast-derived cell line (LS8) to characterize specific responses to fluoride treatment. LS8 cells were growth-inhibited by as little as 1.9-3.8 ppm fluoride, whereas higher doses induced ER stress and caspase-mediated DNA fragmentation. Growth arrest and DNA damage-inducible proteins (GADD153/CHOP, GADD45alpha), binding protein (BiP/glucose-responsive protein 78 (GRP78), the non-secreted form of carbonic anhydrase VI (CA-VI), and active X-box-binding protein-1 (Xbp-1) were all induced significantly after exposure to 38 ppm fluoride. Unexpectedly, DNA fragmentation increased when GADD153 expression was inhibited by short interfering RNA treatment but remained unaffected by transient GADD153 overexpression. Analysis of control and GADD153(-/-) embryonic fibroblasts demonstrated that caspase-3 mediated the increased DNA fragmentation observed in the GADD153 null cells. We also demonstrate that mouse incisor ameloblasts are sensitive to the toxic effects of high dose fluoride in drinking water. Activated Ire1 initiates an ER stress response pathway, and mouse ameloblasts were shown to express activated Ire1. Ire1 levels appeared induced by fluoride treatment, indicating that ER stress may play a role in dental fluorosis. Low dose fluoride, such as that present in fluoridated drinking water, did not induce ER stress.

PMID: 15849362 [PubMed - indexed for MEDLINE]

Penetration of fluoride into natural plaque biofilms.

J Dent Res. 2005 May;84(5):451-5

Authors: Watson PS, Pontefract HA, Devine DA, Shore RC, Nattress BR, Kirkham J, Robinson C

Caries occurs at inaccessible stagnation sites where plaque removal is difficult. Here, the penetration through plaque of protective components, such as fluoride, is likely to be crucial in caries inhibition. We hypothesized that topically applied fluoride would readily penetrate such plaque deposits. In this study, plaque biofilms generated in vivo on natural enamel surfaces were exposed to NaF (1000 ppm F-) for 30 or 120 sec (equivalent to toothbrushing) or for 30 min. Biofilms were then sectioned throughout their depth, and the fluoride content of each section was determined with the use of a fluoride electrode. Exposure to NaF for 30 or 120 sec increased plaque fluoride concentrations near the saliva interface, while concentrations near the enamel surface remained low. Fluoride penetration increased with duration of NaF exposure. Removal of exogenous fluoride resulted in fluoride loss and redistribution. Penetration of fluoride into plaque biofilms during brief topical exposure is restricted, which may limit anti-caries efficacy.

PMID: 15840782 [PubMed - indexed for MEDLINE]

Professionally applied fluoride gel in low-caries 10.5-year-olds.

J Dent Res. 2005 May;84(5):418-21

Authors: Truin GJ, van 't Hof MA

The question has been raised whether low-caries children regularly using fluoride toothpaste will benefit from the professional application of additional fluoride gel. To investigate the caries-reducing effect of semi-annually-applied neutral 1% sodium fluoride gel, we carried out a double-blind randomized controlled clinical trial (n = 594) in a child population, initially aged 9.5-11.5 years, with baseline caries experience of D3MFS = 0 (decayed, missing, and filled tooth surfaces of permanent teeth). The mean number of tooth surfaces saved from caries development by fluoride gel application after 4 years was 0.2 D3MFS (SE = 0.17). The preventive fraction (PF) showed a mean relative effect of professionally applied fluoride gel of 18%. The cariostatic effect of the fluoride gel on pits and fissures would have been influenced by the sealant strategy in the study. Professionally applied fluoride gel showed no statistically significant effect on mean D3MFS score in low-caries 9.5- to 11.5-year-olds.

PMID: 15840776 [PubMed - indexed for MEDLINE]

Fluoride varnish application.

J Am Dent Assoc. 2005 Mar;136(3):283-4; author reply 284

Authors: Smith DM

PMID: 15819341 [PubMed - indexed for MEDLINE]

PrpZ, a Salmonella enterica serovar Typhi serine/threonine protein phosphatase 2C with dual substrate specificity.

Microbiology. 2005 Apr;151(Pt 4):1159-67

Authors: Lai SM, Le Moual H

Genes encoding eukaryotic-type protein kinases and phosphatases are present in many bacterial genomes. An ORF encoding a polypeptide with homology to protein phosphatases 2C (PP2Cs) was identified in the genomes of Salmonella enterica serovar Typhi strains CT18 and Ty2. This protein, termed PrpZ, is the first PP2C to be identified in enterobacteria. Analysis of the amino acid sequence revealed two distinct domains: the N-terminal segment containing motifs of the catalytic domain of PP2Cs and the C-terminal segment with unknown function. PrpZ was expressed in Escherichia coli as a histidine-tagged fusion protein (PrpZ(His)) and the purified protein was analysed for its ability to dephosphorylate various substrates. Using p-nitrophenyl phosphate as a substrate, optimal PrpZ(His) activity was observed at pH 9.5, with a strong preference for Mn(2+) over Mg(2+). Activity of PrpZ(His) was inhibited by EDTA, sodium fluoride, sodium phosphate and sodium pyrophosphate but unaffected by okadaic acid, indicating that PrpZ is a PP2C. Using synthetic phosphopeptides as substrates, PrpZ(His) could hydrolyse phosphorylated serine, threonine or tyrosine residues, with the highest catalytic efficiency (k(cat)/K(m)) for the threonine phosphopeptide. With phosphorylated myelin basic protein (MBP) as the substrate, Mn(2+) was only twofold more efficient than Mg(2+) in stimulating PrpZ(His) activity at pH 8.0. The ability of PrpZ(His) to remove the phosphoryl group from phosphotyrosine residues was confirmed by measuring the release of inorganic phosphate from phospho-Tyr MBP. Together, these data indicate that PrpZ has all the features of a PP2C with dual substrate specificity in vitro.

PMID: 15817783 [PubMed - indexed for MEDLINE]

Comparison of short-term in vitro fluoride release and recharge from four different types of pit-and-fissure sealants.

Bull Tokyo Dent Coll. 2004 Aug;45(3):173-9

Authors: Koga H, Kameyama A, Matsukubo T, Hirai Y, Takaesu Y

OBJECTIVE: The purpose of this in vitro study was to assess the effects of four commercial fluoride-containing pit-and-fissure sealants on caries prevention. MATERIALS AND METHODS: Four sealants containing fluoride, Fuji III, Fuji III LC (GC Co., Tokyo), Teethmate F-1 (Kuraray Medical Co., Osaka) and Helioseal F (Vivadent Co., Liechtenstein) were used to investigate fluoride release and recharge. Disk-shaped specimens prepared from each material were immersed in distilled water at a temperature of 37 degrees C. After seven days, acidulated phosphate fluoride solution (APF) was applied to each specimen, and it was then again immersed in distilled water for 14 days. We then determined how much fluoride had been released into the immersing water. Fuji III LC was used with APF solution to investigate the fluoride uptake. RESULTS: Fuji III had the highest fluoride release, and Fuji III LC had the highest fluoride recharge. Helioseal F and Teethmate F-1 had almost no fluoride recharge. Fuji III LC/APF had a higher fluoride uptake to enamel than Fuji III LC. CONCLUSIONS: These results suggest that GIC-sealants in the oral cavity can serve as a fluoride reservoir and contribute to retaining a low fluoride level in oral fluids, thereby preventing caries.

PMID: 15779460 [PubMed - indexed for MEDLINE]

The effect of a bi-annual professional application of APF foam on dental caries increment in primary teeth: 24-month clinical trial.

J Dent Res. 2005 Mar;84(3):265-8

Authors: Jiang H, Bian Z, Tai BJ, Du MQ, Peng B

The purpose of this study was to evaluate the effect of a bi-annual professional application of acidulated phosphate fluoride (APF) foam on caries increment in the primary dentition over a two-year period in the People's Republic of China. In a double-blind, cluster-randomized, placebo-controlled trial, 392 children aged 3-4 years from 15 classes were randomly assigned to two groups on a school class basis. The experimental group (8 classes) received a bi-annual APF foam application, and the control group (7 classes) received the placebo. The mean increment of dmfs in the experimental group was 24.2% lower than that in the control group (p < 0.05). The significant caries reduction was observed on approximal surfaces in the experimental group compared with the control group (p < 0.01), but there were no differences on occlusal surfaces (p > 0.05). A bi-annual professional application of APF foam was effective in reducing the increment of dental caries in the primary teeth.

PMID: 15723868 [PubMed - indexed for MEDLINE]

Fluoride release from varnishes in two in vitro protocols.

J Am Dent Assoc. 2004 Dec;135(12):1696-9

Authors: Castillo JL, Milgrom P

BACKGROUND: The authors conducted a study to evaluate fluoride released from fluoride varnishes that had been applied with two different protocols. Fluoride release information for these two approaches may allow clinicians to vary application intervals to better meet the needs of their patients. METHODS: The authors painted enamel slabs from exfoliated primary molar teeth either in a single application (five samples) or three times within a single week (five samples) with fluoride varnish (Duraphat, Colgate-Palmolive, New York). The samples were immersed in buffered calcium phosphate solution (pH 6) to simulate the oral environment; the amount of fluoride released was measured during a span of six months. RESULTS: The total release of fluoride was significantly higher in the three-application regimen (34.9 micromoles) than in the single application (23.7 micromol). The rate of release was slower using the three-application regimen. Thus, applying fluoride-release varnish three times in a single week produced greater and longer release of fluoride than did one application. CLINICAL IMPLICATIONS: Massed application of fluoride varnish during a single period during the year may be as effective as spaced single applications. This method can be a good alternative to delivering fluoride varnish to high-caries-risk patients who are mobile or difficult to recall.

PMID: 15646602 [PubMed - indexed for MEDLINE]

Indomethacin enhances shuttling of aquaporin-2 despite decreased abundance in rat kidney.

J Am Soc Nephrol. 2004 Dec;15(12):2998-3005

Authors: Kim SW, Kim JW, Choi KC, Ma SK, Oh Y, Jung JY, Kim J, Lee J

The effect of nonsteroidal antiinflammatory drugs on the regulation of aquaporin-2 (AQP2) water channels in the kidney was determined. Male Sprague-Dawley rats were injected with indomethacin (5 mg/kg twice a day intraperitoneally) for 2 d. The control group was injected with vehicle. The expression of AQP2 proteins was determined in the kidney by immunoblotting and immunohistochemistry. The expression of G(salpha) and type VI adenylyl cyclase was determined by immunoblotting. The activity of adenylyl cyclase complexes was determined by stimulated accumulation of cAMP. Immunoblotting revealed that indomethacin markedly decreased the expression of AQP2. Accordingly, however, the ratio of AQP2 expression in the membrane fraction versus that in the cytoplasmic fraction was increased. The urinary excretion of AQP2 proteins also increased. Immunohistochemistry demonstrated almost exclusive apical labeling of AQP2 with scanty cytoplasmic localization along the collecting duct. The expression of G(salpha) and adenylyl cyclase VI proteins was decreased. The generation of cAMP provoked by arginine vasopressin, sodium fluoride, or forskolin was blunted. These results suggest that indomethacin increases the shuttling of AQP2 while it decreases its abundance in the collecting duct.

PMID: 15579502 [PubMed - indexed for MEDLINE]

Prostaglandin E2--mediated relaxation of the ductus arteriosus: effects of gestational age on g protein-coupled receptor expression, signaling, and vasomotor control.

Circulation. 2004 Oct 19;110(16):2326-32

Authors: Waleh N, Kajino H, Marrache AM, Ginzinger D, Roman C, Seidner SR, Moss TJ, Fouron JC, Vazquez-Tello A, Chemtob S, Clyman RI

BACKGROUND: In the preterm newborn, a patent ductus arteriosus is in large part a result of the increased sensitivity of the immature ductus to prostaglandin E2 (PGE2). PGE2 acts through 3 G protein-coupled receptors (EP2, EP3, and EP4) that activate both adenyl cyclase and K(ATP) channels. We explored these pathways to identify the mechanisms responsible for the increased sensitivity of the immature ductus to PGE2. METHODS AND RESULTS: We measured EP receptor content (mRNA and protein), receptor binding, cAMP production, and isometric tension in rings of ductus taken from immature (65% gestation) and mature (95% gestation) sheep and baboon fetuses. Ductus relaxation and cAMP generation were augmented in response to selective EP receptor agonists in the immature ductus. 8-Br-cAMP, a stable cAMP analogue, produced greater relaxation in the immature ductus. In the presence of a selective protein kinase A inhibitor, Rp-8-CPT cAMPS, the developmental differences in sensitivity to PGE2 could no longer be demonstrated. EP2, EP3, and EP4 receptor densities were higher in immature ductus, despite similar receptor mRNA and protein contents at the 2 gestational ages. In contrast, forskolin and NaF, direct activators of adenyl cyclase and Gs, respectively, elicited comparable increases in cAMP in both age groups. KATP channel inhibition also had similar effects on PGE2-induced relaxation in both age groups. CONCLUSIONS: Two mechanisms explain the increased sensitivity of the immature ductus to PGE2: (1) increased cAMP production because of increased binding of PGE2 to the individual EP receptors and (2) increased potency of cAMP on protein kinase A-regulated pathways.

PMID: 15477420 [PubMed - indexed for MEDLINE]

Protective effect of N-acetylcysteine against oxygen radical-mediated coronary artery injury.

Braz J Med Biol Res. 2004 Aug;37(8):1215-24

Authors: Rodrigues AJ, Evora PR, Schaff HV

The present study investigated the protective effect of N-acetylcysteine (NAC) against oxygen radical-mediated coronary artery injury. Vascular contraction and relaxation were determined in canine coronary arteries immersed in Kreb's solution (95% O2-5% CO2), incubated or not with NAC (10 mM), and exposed to free radicals (FR) generated by xanthine oxidase (100 mU/ml) plus xanthine (0.1 mM). Rings not exposed to FR or NAC were used as controls. The arteries were contracted with 2.5 microM prostaglandin F2alpha. Subsequently, concentration-response curves for acetylcholine, calcium ionophore and sodium fluoride were obtained in the presence of 20 microM indomethacin. Concentration-response curves for bradykinin, calcium ionophore, sodium nitroprusside, and pinacidil were obtained in the presence of indomethacin plus Nomega-nitro-L-arginine (0.2 mM). The oxidative stress reduced the vascular contraction of arteries not exposed to NAC (3.93 +/- 3.42 g), compared to control (8.56 +/- 3.16 g) and to NAC group (9.07 +/- 4.0 g). Additionally, in arteries not exposed to NAC the endothelium-dependent nitric oxide (NO)-dependent relaxation promoted by acetylcholine (1 nM to 10 microM) was also reduced (maximal relaxation of 52.1 +/- 43.2%), compared to control (100%) and NAC group (97.0 +/- 4.3%), as well as the NO/cyclooxygenase-independent receptor-dependent relaxation provoked by bradykinin (1 nM to 10 microM; maximal relaxation of 20.0 +/- 21.2%), compared to control (100%) and NAC group (70.8 +/- 20.0%). The endothelium-independent relaxation elicited by sodium nitroprusside (1 nM to 1 microM) and pinacidil (1 nM to 10 microM) was not affected. In conclusion, the vascular dysfunction caused by the oxidative stress, expressed as reduction of the endothelium-dependent relaxation and of the vascular smooth muscle contraction, was prevented by NAC.

PMID: 15273823 [PubMed - indexed for MEDLINE]

Ghrelin degradation by serum and tissue homogenates: identification of the cleavage sites.

Endocrinology. 2004 Nov;145(11):4997-5005

Authors: De Vriese C, Gregoire F, Lema-Kisoka R, Waelbroeck M, Robberecht P, Delporte C

The endogenous ligand for the GH secretagogue receptor is ghrelin, a peptide recently purified from the stomach. Ghrelin is n-octanoylated on the Ser(3) residue, and this modification is essential for its interaction with the receptor. The degradation of ghrelin by rat and human serum, purified commercial enzymes, and tissues homogenates was analyzed by combining HPLC and mass spectrometry. In serum, ghrelin was desoctanoylated, without proteolysis. The desoctanoylation was significantly reduced by phenylmethylsulfonyl fluoride, a serine proteases and esterases inhibitor. In rat serum, the carboxylesterase inhibitor bis-p-nitrophenyl-phosphate totally inhibited ghrelin desoctanoylation, and a correlation was found between ghrelin desoctanoylation and carboxylesterase activity. Moreover, purified carboxylesterase degraded ghrelin. Thus, carboxylesterase could be responsible for ghrelin desoctanoylation in that species. In human serum, ghrelin desoctanoylation was partially inhibited by eserine salicylate and sodium fluoride, two butyrylcholinesterase inhibitors, but not by bis-p-nitrophenyl-phosphate and EDTA. Purified butyrylcholinesterase was able to degrade ghrelin, and there was a correlation between the butyrylcholinesterase and ghrelin desoctanoylation activities in human sera. This suggested that several esterases, including butyrylcholinesterase, contributed to ghrelin desoctanoylation in human serum. In contact with tissues homogenates, ghrelin was degraded by both desoctanoylation and N-terminal proteolysis. We identified five cleavage sites in ghrelin between residues -Ser(2)-(acyl)Ser(3)- (stomach and liver), -(acyl?)Ser(3)-Phe(4)- (stomach, liver, and kidney), -Phe(4)-Leu(5)- (stomach and kidney), -Leu(5)-Ser(6)- and -Pro(7)-Glu(8)- (kidney). In all cases, the resulting fragments were biologically inactive.

PMID: 15256494 [PubMed - indexed for MEDLINE]

Extended follow-up of cancer incidence in fluoride-exposed workers.

J Natl Cancer Inst. 2004 May 19;96(10):802-3

Authors: Grandjean P, Olsen JH

PMID: 15150310 [PubMed - indexed for MEDLINE]

Bi-directional regulation of Ser-985 phosphorylation of c-met via protein kinase C and protein phosphatase 2A involves c-Met activation and cellular responsiveness to hepatocyte growth factor.

J Biol Chem. 2004 Jun 18;279(25):26445-52

Authors: Hashigasako A, Machide M, Nakamura T, Matsumoto K, Nakamura T

Previous studies indicated that treatment of cells with 12-O-tetradecanoylphorbol-13-acetate induced phosphorylation of Ser-985 at the juxtamembrane of c-Met, the receptor tyrosine kinase for hepatocyte growth factor (HGF), and this was associated with decreased tyrosine phosphorylation of c-Met. However, the regulatory mechanisms and the biological significance of the Ser-985 phosphorylation in c-Met remain unknown. When A549 human lung cancer cells were exposed to oxidative stress with H(2)O(2), H(2)O(2) treatment induced phosphorylation of Ser-985, but this was abrogated by an inhibitor for protein kinase C (PKC). Likewise, treatment of cells with NaF (an inhibitor of protein phosphatases) allowed for phosphorylation of Ser-985, and a protein phosphatase responsible for dephosphorylation of Ser-985 was identified to be protein phosphatase 2A (PP2A). The effects of PKC inhibitors revealed that PKCdelta and -epsilon were responsible for the Ser-985 phosphorylation of c-Met, and pull-down analysis indicated that associations of PKCdelta and -epsilon with c-Met may be involved in the regulation of Ser-985 phosphorylation of c-Met. Instead, PP2A was constitutively associated with c-Met, whereas its activity to dephosphorylate Ser-985 of c-Met was decreased when cells were exposed to H(2)O(2). Addition of HGF to A549 cells in culture induced c-Met tyrosine phosphorylation, the result being mitogenic response and cell scattering. In contrast, in the presence of H(2)O(2) stress, HGF-dependent tyrosine phosphorylation of c-Met was largely suppressed with a reciprocal relationship to Ser-985 phosphorylation, and this event was associated with abrogation of cellular responsiveness to HGF. These results indicate that Ser-985 phosphorylation of c-Met is bi-directionally regulated through PKC and PP2A, and the Ser-985 phosphorylation status may provide a unique mechanism that confers cellular responsiveness/unresponsivenss to HGF, depending on extracellular conditions.

PMID: 15075332 [PubMed - indexed for MEDLINE]