Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa.

OBJECTIVE: The objective of this study was to determine the effect of polyphosphate on intestinal bacterial collagenase production and anastomotic leak in mice undergoing colon surgery. BACKGROUND: We have previously shown that anastomotic leak can be caused by intestinal pathogens that produce collagenase. Because bacteria harbor sensory systems to detect the extracellular concentration of phosphate which controls their virulence, we tested whether local phosphate administration in the form of polyphosphate could attenuate pathogen virulence and prevent leak without affecting bacterial growth. METHODS: Groups of mice underwent a colorectal anastomosis which was then exposed to collagenolytic strains of either Serratia marcescens or Pseudomonas aeruginosa via enema. Mice were then randomly assigned to drink water or water supplemented with a 6-mer of polyphosphate (PPi-6). All mice were sacrificed on postoperative day 10 and anastomoses assessed for leakage, the presence of collagenolytic bacteria, and anastomotic PPi-6 concentration. RESULTS: PPi-6 markedly attenuated collagenase and biofilm production, and also swimming and swarming motility in both S. marcescens and P. aeruginosa while supporting their normal growth. Mice drinking PPi-6 demonstrated increased levels of PPi-6 and decreased colonization of S. marcescens and P. aeruginosa, and collagenase activity at anastomotic tissues. PPi-6 prevented anastomotic abscess formation and leak in mice after anastomotic exposure to S. marcescens and P. aeruginosa. CONCLUSIONS: Polyphosphate administration may be an alternative approach to prevent anastomotic leak induced by collagenolytic bacteria with the advantage of preserving the intestinal microbiome and its colonization resistance.

Anti-plaque and antimicrobial efficiency of different oral rinses in a 3-day plaque accumulation model.

The idea of incorporating a mouthrinse with normal tooth brushing could be a useful adjunct to oral hygiene. Despite the principle nature of the toothpaste vehicle, most alcohol-based chemical plaque-control agents have been evaluated and later formulated in the mouthrinse vehicle. The current study was aimed to investigate the persistence of antimicrobial action and plaque inhibitory properties of a new alcohol-free mouthrinse when compared with positive control, chlorhexidine 0.12% and placebo control, physiologic saline solution mouthrinses. The evaluation of the antimicrobial activity was performed by saliva samples collected during the 3 days of usage. The results of this study indicate that this new oral rinse has an equivalent plaque inhibitory action to chlorhexidine, and the plaque inhibitory action of the rinse appears to be derived from a persistence of antimicrobial action in the mouth. Furthermore, no side effects were reported during the study, and the additional benefit of no alcohol presence in the rinse solution.

Effect of toothpaste with nano-sized trimetaphosphate on dental caries: In situ study.

OBJECTIVES: This in situ study was to evaluate the remineralizing effect of a fluoride toothpaste supplemented with nano-sized sodium trimetaphosphate (TMP). METHODS: This blind and cross-over study was performed in 4 phases of 3 days each. Twelve subjects used palatal appliances containing four bovine enamel blocks with artificial caries lesions. Volunteers were randomly assigned into the following treatment groups: Placebo (without F and TMP); 1100 ppm F (1100), 1100 supplemented with 3% micrometric TMP (1100 TMP) and with nano-sized TMP (1100 TMPnano). Volunteers were instructed to brush their natural teeth with the palatal appliances in the mouth during 1min (3 times/day), so that blocks were treated with natural slurries of toothpastes. After each phase, the percentage of surface hardness recovery (%SHR), integrated mineral recovery (IMR) and integrated differential mineral area profile (ΔIMR) in enamel lesions were calculated. F in enamel was also determined. Data were analyzed by ANOVA and Student-Newman-Keuls test. RESULTS: Enamel surface became 20% harder when treated with 1100 TMPnano in comparison with 1100 (p<0.001). 1100 TMPnano showed remineralizing capacity (IMR; ΔIMR) 66% higher when compared with 1100 TMP (p<0.001). Enamel F uptake in the 1100 TMPnano group was 2-fold higher when compared to its counterpart without TMP (p<0.001). CONCLUSION: The addition of 3% TMPnano to a conventional toothpaste was able to promote an additional remineralizing effect of artificial caries lesions. CLINICAL SIGNIFICANCE: Toothpaste containing 1100 ppm F associated with TMPnano showed a potential of higher remineralization to 1100 ppm F and 1100 ppm F micrometric TMP.

In situ remineralizing effect of fluoride varnishes containing sodium trimetaphosphate.

OBJECTIVE: This study analyzed the effects of a fluoride (F) varnish supplemented with sodium trimetaphosphate (TMP) on the remineralization of caries-like lesions in situ. MATERIALS AND METHODS: Twelve subjects used palatal devices with demineralized enamel discs for 3 days, following a double-blind, crossover protocol. Test groups included placebo (no F or TMP), 5% NaF and 5% NaF/5% TMP varnishes. The percentage of surface hardness recovery (%SHR) and cross-sectional hardness (ΔKHN) were determined. RESULTS: Significant differences were observed among all varnishes regarding %SHR and ΔKHN. The highest %SHR and the lowest ΔKHN were seen for the 5% NaF/5% TMP varnish, followed by 5% NaF and placebo. CONCLUSION: The remineralizing effect of a 5% NaF varnish is significantly enhanced when associated with TMP. CLINICAL RELEVANCE: The reduction in the subsurface lesion area of enamel treated with the TMP-containing varnish implies that cavities would take longer to develop or might not develop at all depending on individual factors, resulting in lower net caries increments at individual and population levels.

Efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye: a systematic review of randomized clinical trials.

PURPOSE: To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye. METHODS: Randomized clinical trials (RCTs) from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were identified to evaluate the efficacy and safety of topical administration of diquafosol to patients with dry eyes. Data evaluation was based on endpoints including Schirmer test, tear film break-up time, ocular surface staining score, subjective symptom score, and adverse events. RESULTS: A total of 8 RCTs involving 1516 patients were selected based on the prespecified criteria. Significant improvement of Schirmer test values and tear film break-up time were reported in 40% (2 of 5) and 80% (4 of 5) studies, respectively. Ocular surface staining scores significantly decreased in 100% (fluorescein corneal staining, 6 of 6; Rose Bengal corneal and conjunctival staining, 4 of 4) RCTs. Symptoms significantly improved in 75% (6 of 8) RCTs in patients with dry eyes. No severe adverse events were reported with the concentration of diquafosol from 0.5% to 5%. Heterogeneity in study design prevented meta-analysis from statistical integration and summarization. CONCLUSIONS: Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.

Effect of fluoride gels supplemented with sodium trimetaphosphate in reducing demineralization.

OBJECTIVES: The objective of this study was to evaluate the in vitro effect of low-fluoride (F) gels supplemented with sodium trimetaphosphate (TMP) on enamel demineralization. MATERIALS AND METHODS: Bovine enamel blocks (n = 160) were selected based on surface hardness (SH) and divided into eight treatment groups (n = 20 per group): no F or TMP (placebo), 3 % TMP (3 %TMP), 5 % TMP (5 %TMP), 4,500 µg F/g (4,500), 4,500 µg F/g + 3 % TMP (4,500 3 %TMP), 4,500 µg F/g + 5 % TMP (4,500 5 %TMP), 9,000 µg F/g (9,000), and 12,300 µg F/g (acid gel). Blocks were subjected to demineralization/remineralization cycling for 5 days. Subsequently, surface hardness (SH1) and integrated loss of subsurface hardness (ΔKHN) were assessed, and the concentrations of loosely bound (CaF2-like) and firmly bound (FA-like) formed and retained F were determined. RESULTS: The 4,500 5 %TMP and acid gel groups showed similar results and had the lowest mineral loss (SH1 and ∆KHN). The acid gel group had the highest concentration of CaF2-like F, but the formation and retention of FA-like F was greater in the 4,500 5 %TMP group than in the acid gel group (p < 0.05). CONCLUSION: It is possible to inhibit enamel demineralization with low-F gels supplementing these gels with 5 % TMP. CLINICAL RELEVANCE: The low-F gel containing TMP can be regarded as a safer alternative for clinical use from a toxicological point of view since it contains half of the amount of a conventional formulation while promoting similar anticaries effect.

Effect of sodium trimetaphosphate on hydroxyapatite solubility: an in vitro study.

This study evaluated the effect of different concentrations of sodium trimetaphosphate (TMP) with and without fluoride (F) on the concentration of calcium (Ca), phosphorus (P) and F in hydroxyapatite (HA). Synthetic HA powder (0.15 g) was suspended (n=6) in solutions (75 mL) of TMP at 0%, 0.1%, 0.2%, 0.4%, 0.6%, 0.8%, 1.0%, 2.0%, 4.0%, 6.0%, 8.0% and 10% concentrations in the presence and absence of 100 ppm F and subjected to a pH-cycling process. The precipitates were filtrated, dried at 70° C for 24 h and ground onto a fine powder. The concentrations of F (KOH (CaF2) and HCl (FA) soluble), Ca (Arsenazo III), and P (molybdate method) in HA were determined. The Ca P, and Ca/P ratio data were subjected to Tukey's test and the F data were subjected to Student-Newman-Keuls test (p<0.05). The addition of TMP to the samples reduced F deposition to 98% (p<0.001). The groups containing 100 ppm F and 0.4% or 0.6% TMP exhibited a higher Ca concentration than the group containing only 100 ppm F (p<0.05). Furthermore, the HA treated with 0.2% and 0.4% TMP and 100 ppm F showed a higher Ca/P ratio than the other groups (p<0.001). In conclusion, TMP at 0.2%, 0.4% and 0.6% concentrations combined with F seemed to be able to precipitate HA with low solubility. However, especially at high concentrations, TMP interferes with F deposition on HA.

In situ evaluation of a low fluoride concentration gel with sodium trimetaphosphate in enamel remineralization.

PURPOSE: To evaluate the capability of gels with low fluoride (F) concentration and supplemented with sodium trimetaphosphate (TMP) to promote in situ enamel remineralization. METHODS: Bovine enamel blocks were selected on the basis of their surface hardness after demineralization, and divided into five groups: gel without F or TMP (placebo); gel with 4,500 ppm F (4,500); gel with 4,500 ppm F + 5% TMP (4,500 5% TMP); gel with 9,000 ppm F (9,000) and gel with 12,300 ppm F (12,300). The study design was blind and cross-over: 12 subjects used palatal devices with four demineralized enamel blocks for 3 days, after topical fluoride application (TFA). Two blocks were removed immediately for analysis of the loosely bound fluoride (CaF2) and firmly bound fluoride (F) after TFA in enamel. In the remaining blocks, the percentage of surface hardness recovery (% SH), cross-sectional hardness (deltaKHN) and CaF2 and F were determined after remineralization. The results were subjected to ANOVA and Bonferroni tests (P < 0.05). RESULTS: The groups 4,500 5% TMP, 9,000, and 12,300 showed the best results with regard to % SH (P < 0.05). Lower deltaKHN values were observed in the 4,500 5% TMP and 12,300 gel groups (P < 0.05). Higher concentrations of CaF2 and F were observed in the 12,300 group, followed by the 4,500 5% TMP and 9,000 groups (P > 0.05). It was concluded that it is possible to promote enamel remineralization using gels with low fluoride concentration supplemented with TMP.

Effect of Sodium Trimetaphosphate on Hydroxyapatite Solubility: An In Vitro Study

This study evaluated the effect of different concentrations of sodium trimetaphosphate (TMP) with and without fluoride (F) on the concentration of calcium (Ca), phosphorus (P) and F in hydroxyapatite (HA). Synthetic HA powder (0.15 g) was suspended (n=6) in solutions (75 mL) of TMP at 0%, 0.1%, 0.2%, 0.4%, 0.6%, 0.8%, 1.0%, 2.0%, 4.0%, 6.0%, 8.0% and 10% concentrations in the presence and absence of 100 ppm F and subjected to a pH-cycling process. The precipitates were filtrated, dried at 70° C for 24 h and ground onto a fine powder. The concentrations of F (KOH (CaF2) and HCl (FA) soluble), Ca (Arsenazo III), and P (molybdate method) in HA were determined. The Ca P, and Ca/P ratio data were subjected to Tukey's test and the F data were subjected to Student-Newman-Keuls test (p<0.05). The addition of TMP to the samples reduced F deposition to 98% (p<0.001). The groups containing 100 ppm F and 0.4% or 0.6% TMP exhibited a higher Ca concentration than the group containing only 100 ppm F (p<0.05). Furthermore, the HA treated with 0.2% and 0.4% TMP and 100 ppm F showed a higher Ca/P ratio than the other groups (p<0.001). In conclusion, TMP at 0.2%, 0.4% and 0.6% concentrations combined with F seemed to be able to precipitate HA with low solubility. However, especially at high concentrations, TMP interferes with F deposition on HA.

Este estudo avaliou o efeito de diferentes concentrações de trimetafosfato de sódio (TMP) com e sem fluoreto (F) nas concentrações de cálcio (Ca), fósforo (P) e F na hidroxiapatita (HA). Pó de HA sintético (0,15 g) foi suspenso (n=6) em soluções (75 mL) de TMP com concentrações de 0%, 0,1%, 0,2%, 0,4%, 0,6%, 0,8%, 1,0%, 2,0%, 4,0%, 6,0%, 8,0% e 10% na presença ou na ausência de 100 ppm F e foram submetidas ao processo de ciclagem de pH. O precipitado foi filtrado seco a 70°C por 24 h e triturado em um pó fino. As concentrações de F (solúvel em KOH: CaF2, e em HCl: FA), Ca (Arsenazo III) e P (método do molibdato) foram determinadas na HA. Os dados de Ca, P e de proporção Ca/P foram submetidos ao teste de Tukey e os dados de F ao teste Student-Newman-Keuls (p<0,05). A adição de TMP reduziu a deposição de F em 98% (p<0,001). Os grupos contendo 100 ppm F e TMP 0,4% e 0,6% apresentaram maiores concentrações de Ca do que o grupo contendo somente 100 ppm F (p<0,05). Além disso, a HA tratada com 0,2% e 0,4% de TMP e 100 ppm F apresentou maiores proporções Ca/P em relação aos demais grupos (p<0,001). Em conclusão, TMP nas concentrações de 0,2%, 0,4% e 0,6% quando associado ao F é capaz de precipitar uma HA com menor solubilidade. Entretanto, especialmente em altas concentrações, TMP interfere com a deposição de F na HA.

Mono- and polyphosphates have similar effects on calcium and phosphorus metabolism in healthy young women.

PURPOSE: Phosphate (Pi) salts, often mono- (MP) or polyphosphates (PP), are commonly used as additives in the food industry. Previous studies have shown that the effects of MP and PP on calcium (Ca) and phosphorus (P) metabolism may differ. The aim of this study was to determine whether the effects of MP and PP salts differ on markers of Ca and P metabolism in young women. METHODS: Fourteen healthy women 19-31 years of age were randomized into three controlled 24-h study sessions, each subject serving as her own control. During each session, the subjects received three doses of MP, PP or a placebo with meals in randomized order. Both Pi salts provided 1,500 mg P/d, and the diet during each session was identical. Markers of Ca and P metabolism were followed six times over 24 h. RESULTS: During both MP and PP sessions, we found an increase in serum phosphate (S-Pi, p = 0.0001), urinary phosphate (U-Pi, p = 0.0001) and serum parathyroid hormone (S-PTH, p = 0.048 MP, p = 0.012 PP) relative to the control session. PP decreased U-Ca more than did MP (p = 0.014). CONCLUSIONS: The results suggest that PP binds Ca in the intestine more than does MP. Based on the S-Pi, U-Pi and S-PTH results, both Pi salts are absorbed with equal efficiency. In the long run, increased S-PTH, caused by either an MP or PP salt, could have negative effects on bone metabolism.

Evaluation of different fluoride concentrations supplemented with trimetaphosphate on enamel de- and remineralization in vitro.

Trimetaphosphate (TMP) effects on demineralized bovine enamel were studied after 15 days of pH cycling. Treatments included 30 wt% (weight percent) dilutions of 0, 500, 1,500 or 3,000 µg F/g aqueous NaF solutions with or without 3% TMP. Treated specimens were assessed by transverse microradiography. With the exception of the 3,000 µg F/g case, 3% TMP addition provided significant additional overall remineralization compared with F alone. Mineral content profiles differed significantly between corresponding F and F + TMP groups. Fluoride alone resulted in more remineralization in the original demineralized zone, whereas F + TMP caused less demineralization in the underlying, originally sound enamel.

Effect on dental stain occurrence by chewing gum containing sodium tripolyphosphate--a double-blind six-week trial.

OBJECTIVE: A six-week controlled double-blind clinical study was conducted to assess and to measure the efficacy of a sugar-free chewing gum containing sodium tripolyphosphate (1%) on dental stain occurrence versus a placebo sugar-free chewing gum. METHODS: One-hundred and eleven subjects who had a Lobene Modified Index for stain extent score between 0.33 and 1.5 in their frontal teeth joined this study. Each subject entered in the test or the control group using a random table which allowed for an equal distribution of smokers and habitual tea users. Participants agreed to chew two gums (two grams each) three times per day, after meals, for ten minutes over six weeks. All received the same dentifrice containing only fluoride as the active agent. After six weeks, participants were scored for dental stain with the Lobene Modified Index. Data were scored by the same blinded operator for all measurements. Comparisons between the groups with respect to baseline scores were performed using an unpaired t-test, and inside the groups with a paired t-test (alpha = 0.05). RESULTS: One-hundred and eight subjects completed the trial; three left, but none reported problems linked to sodium tripolyphosphate. The mean difference for stain extent index after the six-week trial was 0.04 (+/- 0.08) in the control group, and -0.05 (+/- 0.08) in the test group (p < 0.001). A statistically significant reduction was also reported for intensity and composite indexes. The initial mean for stain extent index in the test group was 0.8 (+/- 0.34), and at six weeks was 0.74 (+/- 0.33; p < 0.001). The initial mean for extent index in the control group was 0.78 (+/- 0.3), and at six weeks was 0.81 (+/- 0.32; p < 0.005). CONCLUSION: This trial showed a reduction in dental stain by a chewing gum containing sodium tripolyphosphate after six weeks.

In vitro evaluation of dentifrice with low fluoride content supplemented with trimetaphosphate.

One way to reduce dental fluorosis is by reducing the fluoride (F) concentration in dentifrice, but low-F dentifrice should be as effective as a standard dentifrice. This study evaluated in vitro whether the supplementation with sodium trimetaphosphate (TMP) of a dentifrice with low F content (500 microg/g) would provide a similar effect to that of a standard dentifrice. Bovine enamel blocks were submitted to a pH cycling regime incorporating daily exposures to a slurry of dentifrice: a low-F dentifrice with or without 0.1-3.0% TMP; an F-free, phosphate-free dentifrice (negative control), or a dentifrice with 1,100 microg/g F (positive control). The addition of TMP to dentifrice with or without F was associated with higher surface hardness and decreased loss of integrated subsurface hardness after pH cycling. The combination of 1% TMP and 500 microg F/g had a greater effect than the positive control dentifrice. It is concluded that the addition of TMP to the 500-microg F/g dentifrice allowed a similar or larger effect as compared with a standard dentifrice in this in vitro model.

Comparison of various phosphate salts as the dietary phosphorus source on nephrocalcinosis and kidney function in rats.

The effects of various phosphate salts as the dietary phosphorus sources on the development of nephrocalcinosis and kidney function were examined in rats fed diets containing monophosphate salts (sodium dihydrogenphosphate, NaH2PO4, or potassium dihydrogenphosphate, KH2PO4) or polyphosphate salts (sodium tripolyphosphate, Na5P3O10, or potassium tripolyphosphate, K5P3O10), at levels representing normal phosphorus (normal phosphorus diet) or high phosphorus (high phosphorus diet) contents for 21 d. High phosphorus diet-feeding increased the kidney calcium and phosphorus concentrations. Kidney calcium and phosphorus concentrations were higher in rats fed the high phosphorus diet containing Na5P3O10 or K5P3O10 than in rats fed the high phosphorus diet containing NaH2PO4 or KH2PO4. Nephrocalcinosis was observed in all rats fed a high phosphorus diet, and the degree of nephrocalcinosis was more severe in rats fed Na5P3O10 or K5P3O10 than in rats fed NaH2PO4 or KH2PO4. In rats fed the high phosphorus diet, creatinine clearance was higher in rats fed Na5P3O10 or K5P3O10 than in rats fed NaH2PO4 or KH2PO4. In rats fed Na5P3O10 or K5P3O10, urinary albumin excretion and N-acetyl-beta-D-glucosaminidase (NAG) activity in the urine were increased in rats fed the high phosphorus diet. These were higher in rats fed the high phosphorus diet containing Na5P3O10 than in rats fed the high phosphorus diet containing NaH2PO4 or KH2PO4. This study observed that the development of nephrocalcinosis and kidney function in rats fed the high phosphorus diet was influenced by the difference in monophosphate or polyphosphate salts provided as the dietary phosphorus source, while the effects of sodium and potassium salts were not evident. We suggest that the development of nephrocalcinosis and kidney function in rats fed a high phosphorus diet was altered depending on the form of phosphate salts provided as the dietary source of phosphorus. Additionally, the development of nephrocalcinosis and diminished kidney function in rats fed the high phosphorus diet was more severe for polyphosphate salts as compared to monophosphate salts.