Effects of eye drops containing a mixture of 3% diquafosol sodium and tocopherol acetate (vitamin E) on the ocular surface of murine dry eye.

PURPOSE: To investigate the efficacy of topical application of 3% diquafosol sodium (DQS) and tocopherol (TCP) acetate mixtures in a mouse model of experimental dry eye (EDE). METHODS: After exposure to desiccating stress for 5 days, eye drops consisting of 3% DQS alone, 0.01% TCP alone, or 3% DQS and 0.005% or 0.01% TCP mixture were applied for the treatment of EDE. Tear volume, tear film break-up time (TBUT), corneal fluorescein staining scores (CFSS), and tear film lipid layer grades (TFLLG) were measured at 0, 5 and 10 days after treatment. The 2',7'-dichlorodihydrofluorescein diacetate assay (DCFDA) for reactive oxygen species (ROS) production, enzyme-linked immunosorbent assay (ELISA) for malondialdehyde (MDA), and flow cytometry for CD4 + interferon (IFN)-γ+ T cells were evaluated on the ocular surface at 10 days after treatment. In addition, levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and chemokine CC motif ligand 4 (CCL4) in the conjunctiva were measured using a multiplex immunobead assay, and conjunctival goblet cells were counted by periodic acid-Schiff staining at 10 days after treatment. RESULTS: Both the TCP mixture groups indicated a significant improvement in TBUT, ROS production, and MDA concentrations compared to those in the DQS alone group. Furthermore, the 0.01% TCP mixture group also showed higher tear film lipid layer grades and conjunctival goblet cell density and lower corneal fluorescein staining scores, number of CD4 + IFN-γ+ T cells, and levels of TNF-α, IL-1ß, and CCL4 than the DQS alone group (P < 0.05). CONCLUSIONS: Application of eye drops containing the mixture of DQS and TCP could stabilize the tear film lipid layer, improve TBUT and corneal epithelial damages, decrease ROS production, inflammatory molecules, and T cells, and increase conjunctival goblet cell density on the ocular surface. Topical DQS and TCP mixtures may have a greater therapeutic effect on clinical signs, oxidative damage, and inflammation of dry eye than DQS eye drops.

Can We Improve Stavudine's Safety Profile in Children? Pharmacokinetics of Intracellular Stavudine Triphosphate with Reduced Dosing.

Stavudine remains a useful replacement option for treatment for HIV+ children. WHO reduced the adult dose to 30 mg twice daily, which maintains efficacy and lowers mitochondrial toxicity. We explored intracellular stavudine triphosphate levels in children receiving a reduced dose of 0.5 to 0.75 mg/kg of body weight twice daily to investigate whether a similar dose optimization can safely be made. A population pharmacokinetic model was developed to describe the pharmacokinetics of intracellular stavudine triphosphate in 23 HIV+ children and 24 HIV+ adults who received stavudine at 0.5 mg/kg and 20 mg twice daily for 7 days, respectively. Simulations were employed to optimize the pediatric dosing regimen to match exposures in adults receiving the current WHO-recommended dose of 30 mg twice daily. A biphasic disposition model with first-order appearance and disappearance described the pharmacokinetics of stavudine triphosphate. The use of allometric scaling with fat-free mass characterized well the pharmacokinetics in both adults and children, and no other significant effect could be detected. Simulations of 30 mg twice daily in adults predicted median (interquartile range [IQR]) stavudine triphosphate minimum drug concentration (Cmin) and maximum drug concentration (Cmax) values of 13 (10 to 19) and 45 (38 to 53) fmol/106 cells, respectively. Targeting this exposure, simulations in HIV+ children were used to identify a suitable weight-band dosing approach (0.5 to 0.75 mg/kg), which was predicted to achieve median (IQR) Cmin and Cmax values of 13 (9 to 18) and 49 (40 to 58) fmol/106 cells, respectively. Weight-band dosing using a stavudine dose of 0.5 to 0.75 mg/kg is proposed, and it shows comparable exposures to adults receiving the current WHO-recommended dose of 30 mg twice daily. Our pharmacokinetic results suggest that the decreased stavudine dose in children >2 years would have a reduced toxic effect while retaining antiretroviral efficacy.

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.

The effects of 3% diquafosol sodium eye drop application on meibomian gland and ocular surface alterations in the Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice.

PURPOSE: The purpose of the study is to investigate the effect of 3% diquafosol sodium eye drops on meibomian gland and ocular surface alterations in the superoxide dismutase-1 (Sod1 -/- ) mice in comparison to the wild-type mouse. METHODS: Three percent diquafosol sodium eye drop was instilled to 20 eyes of 10 50-week-old male Sod1 -/- mice and 22 eyes of 11 C57BL/6 strain 50-week-old wild-type (WT) male mice six times a day for 2 weeks. Aqueous tear secretion quantity was measured with phenol red-impregnated cotton threads without anesthesia. Tear film stability and corneal epithelial damage were assessed by fluorescein and lissamine green staining. We also performed oil red O (ORO) lipid staining to evaluate the lipid changes in the meibomian glands. Meibomian gland specimens underwent hematoxylin and eosin staining to examine histopathological changes and meibomian gland acinar unit density after sacrifice. Immunohistochemistry staining was performed using cytokeratin 4, cytokeratin 13, and transglutaminase-1 antibodies. Quantitative real-time polymerase chain reaction for cytokeratin 4, cytokeratin 13, and transglutaminase-1 mRNA expression was also performed. RESULTS: The aqueous tear quantity, the mean tear film breakup time, and the number of lipid droplets significantly improved in the Sod1 -/- mice with treatment. The mean meibomian acinar unit density did not change in the Sod1 -/- mice and WT mice after treatment. Application of 3% diquafosol sodium eye drop significantly decreased the corneal fluorescein and lissamine green staining scores in the Sod1 -/- mice after 2 weeks. We showed a notable increase in cytokeratin 4, cytokeratin 13 immunohistochemistry staining, and cytokeratin 4, cytokeratin 13 mRNA expressions with a marked decrease in immunohistochemistry staining and significant decline in mRNA expression of transglutaminase-1 after 3% diquafosol sodium treatment. CONCLUSION: Topical application of 3% diquafosol sodium eye drop improved the number of lipid droplets, tear stability, and tear production which in turn appeared to have a favorable effect on the ocular surface epithelium. Three percent diquafosol sodium eye drop may be a potential treatment for age-related meibomian gland and dry eye disease based on the observations of the current study.

Therapeutic effects of 3% diquafosol ophthalmic solution in patients with short tear film break-up time-type dry eye disease.

BACKGROUND: To investigate therapeutic effects of topical diquafosol tetrasodium 3% ophthalmic solution in patients with short tear film break-up time (TFBUT)-type dry eye (DE). METHODS: The prospective study was performed in 70 eyes of 70 patients with short TFBUT-type DE. Diagnosis of short TFBUT-type DE was made based on the presence of DE symptoms, TFBUT value ≤5 s, corneoconjunctival staining score ≤ 2 (on a scale of 0 to 4), and Schirmer I value > 5 mm. Patients with systemic immunologic disorders or ocular graft-versus-host disease were excluded. Before and after instillation of 3% diquafosol ophthalmic solution six times per day for 4 weeks, subjective DE symptoms, TFBUT, corneoconjunctival staining score, and Schirmer I value were examined and compared. Also, demographic factors were compared between patients who showed improvement in each DE parameter by treatment and those who did not. RESULTS: Four-week treatment with 3% diquafosol ophthalmic solution significantly improved DE symptoms (p < 0.0001), increased TFBUT (p < 0.0001), and reduced corneoconjunctival staining scores (p < 0.0001). Schirmer I values were not changed by treatment. The age of patients who showed improvement in subjective DE symptoms after treatment was significantly lower than that of patients who did not (53.4 ± 27.5 vs. 63.3 ± 13.9 years, p = 0.012). Ocular side effects developed in 3 patients (4.3%), including conjunctival chemosis (n = 1) and persistent stinging sensation (n = 2). CONCLUSIONS: Diquafosol tetrasodium 3% ophthalmic solution is effective in improving subjective symptoms and tear film stability in short TFBUT-type DE patients. TRIAL REGISTRATION: The study was retrospectively registered on Clinical Research Information Service (CRiS), Republic of Korea. TRIAL REGISTRATION NUMBER: KCT0003134 . Date of registration: 2018-08-15.

Long-Term Topical Diquafosol Tetrasodium Treatment of Dry Eye Disease Caused by Chronic Graft-Versus-Host Disease: A Retrospective Study.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of long-term use of 3% diquafosol ophthalmic solution (DQS), an eye drop for mucin production and water secretion, for treating dry eye disease (DED) caused by chronic graft-versus-host disease (cGVHD). METHODS: We retrospectively evaluated the safety and efficacy of DQS in 10 patients with mild to moderate cGVHD-induced DED. The efficacy was assessed by (1) degree of symptoms, (2) Schirmer I test value, (3) tear film breakup time (TFBUT), and (4) fluorescein and rose bengal scores. RESULTS: The median duration of DQS treatment was 12.0 months (range 6-17 months). DQS was effective for relieving severe pain caused by cGVHD-related DED. Although the Schirmer I test value was enhanced only marginally, the long-term application of DQS significantly improved the corneal/conjunctival epitheliopathy and tear film stability: the fluorescein score improved from 5.9±0.6 to 1.3±1.1 points (P=1.771×10); rose bengal staining from 4.7±1.6 to 2.0±1.5 points (P=0.008); and TFBUT from 2.6±0.9 to 4.6±1.6 mm (P=0.009). Furthermore, the long-term DQS treatment caused no major adverse events. CONCLUSIONS: This study suggested that long-term DQS treatment is a safe and robust approach for alleviating cGVHD-related DED.

Preparation and characterisation of flame retardant encapsulated with functionalised silica-based shell.

Intumescent fire retardant (IFR) coatings are nowadays considered as the most effective flame retardant (FR) treatment. Nevertheless, the principal compound in an IFR system, ammonium polyphosphate (APP), is highly sensitive to moisture and IFR coating effectiveness decreases quickly. The main objective of this study is to encapsulate APP in a hybrid silica-based membrane by sol-gel process using alkoxysilane tetraethoxysilane (TEOS) and methyltriethoxysilane (MTES) precursor. The morphology and structure of APP and microencapsulated ammonium polyphosphate (MAPP) were assessed by scanning electron microscopy and Fourier transforms infrared spectroscopy (FTIR). X-ray photoelectron spectroscopy (XPS) results revealed that APP was well encapsulated inside the polysiloxane shells. The thermal degradation of APP and MAPP was evaluated by thermogravimetric analysis. At 800 °C, the MAPP had higher char residue (70.49 wt%) than APP (3.06 wt%). The hydrophobicity of MAPP increased significantly with the water contact angles up to 98°, in comparison to 20° for APP.

Effect of diquafosol tetrasodium 3% on the conjunctival surface and clinical findings after cataract surgery in patients with dry eye.

PURPOSE: To investigate the effects of diquafosol tetrasodium (DT) 3% on conjunctival impression cytologic findings in addition to clinical symptoms and signs after cataract surgery in patients with preexisting dry eye disease (DED). METHODS: Ninety-four eyes of 94 patients with DED who underwent uneventful cataract surgery were included. In total, 50 patients were treated with DT 3% (group A), while 44 patients were treated with sodium hyaluronate 0.1% (group B) postoperatively, along with topical antibiotics and steroids. Conjunctival impression cytology was performed at baseline and at 4 and 12 weeks after surgery. Visual acuity, ocular surface disease index (OSDI), tear film breakup time (TBUT), keratoepitheliopathy score, Schirmer's test, and tear clearance rate were measured at baseline and at 1, 4, and 12 weeks, and corneal aberration was analyzed at baseline and at 4 and 12 weeks. RESULTS: The grade of conjunctival squamous metaplasia was lower at 12 weeks, and goblet cell density was higher at 4 and 12 weeks in group A than in group B (P < 0.05). Compared with group B, group A showed significantly lower OSDI scores at 4 and 12 weeks, longer TBUT at 1, 4, and 12 weeks, lower keratoepitheliopathy scores at 1 and 12 weeks, and lower total root-mean-square score and spherical aberrations at 4 weeks after surgery (P < 0.05). CONCLUSIONS: DT 3% eye drops application after cataract surgery was effective in improving conjunctival epithelial morphology and goblet cell density as well as clinical findings in patients with DED.

Inorganic polyphosphate enhances radio-sensitivity in a human non-small cell lung cancer cell line, H1299.

Inorganic polyphosphate is a linear polymer containing tens to hundreds of orthophosphate residues linked by high-energy phosphoanhydride bonds. Polyphosphate has been recognized as a potent anti-metastasis reagent. However, the molecular mechanism underlying polyphosphate action on cancer cells is poorly understood. In this study, we investigated the involvement of polyphosphate in radio-sensitivity using a human non-small cell lung cancer cell line, H1299. We found that polyphosphate treatment decreases cellular adenosine triphosphate levels, suggesting a disruption of energy metabolism. We also found that the induction of DNA double-strand breaks was enhanced in polyphosphate-treated cells after X-ray irradiation and colony formation assay revealed that cell survival decreased compared with that of the control groups. These findings suggest that polyphosphate is a promising radio-sensitizer for cancer cells. Therefore, we hypothesized that polyphosphate treatment disrupts adenosine triphosphate-mediated energy transfer for cellular survival and DNA repair, thereby reducing the cellular capability to resist X-ray irradiation.

Effects of sodium tri- and hexameta-phosphate in vitro osteoblastic differentiation in Periodontal Ligament and Osteoblasts, and in vivo bone regeneration.

The present study was designed to assess the effects and underlying mechanism of two poly(P) compounds, sodium triphosphate (STP, Na5P3O10) and sodium hexametaphosphate (SHMP, Na15P13O40~Na20P18O40) on osteoblastic differentiation of human periodontal ligament cells (PDLCs) and osteoblasts in vitro, and bone formation in vivo. Differentiation was assessed by alkaline phosphatase (ALP) activity, mineralization, and mRNA expression for marker genes. To examine the osteogenic potential to regenerate bone, the critical-sized mouse calvarial defect model was utilized. Incubation of PDLCs and osteoblasts with STP and SHMP resulted in a dose- and time-dependent increase in growth, alkaline phosphatase (ALP) activity, mineralization and mRNA expression for marker genes. STP and SHMP increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), Akt, and mammalian target of rapamycin (mTOR), and mitogen-activated protein kinases (MAPK). Treatment with the mTOR inhibitor, rapamycin, attenuatted STP- and SHMP-induced osteoblastic differentiation. Micro-CT and histologic analysis showed that STP significantly increased new bone formation in calvarial defects, compared with SHMP and control group. Collectively, this is the first study to demonstrate that STP and SHMP promotes the osteoblastic differentiation in vitro, whereas STP only stimulated bone repair in vivo. Therefore, STP may be useful therapeutic approach for the regeneration of bone or periodontal tissue.

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.

Intraocular Scattering after Instillation of Diquafosol Ophthalmic Solution.

PURPOSE: To assess the changes in intraocular scattering before and after instillation of diquafosol ophthalmic solution in patients with short tear breakup time (TBUT) dry eye. METHODS: We prospectively examined 20 eyes of 20 short TBUT dry eye patients (study group) and age-matched 20 eyes of 20 healthy subjects (control group). Intraocular scattering was measured as the objective scattering index (OSI) at 0.5-second intervals over 10 seconds without blinking. Patients were instructed to start topical administration of 3% diquafosol ophthalmic solution six times daily for 4 weeks. RESULTS: The OSI significantly deteriorated after 7.0 seconds compared with the initial value of OSI after the blinking in the study group. The OSI was also significantly higher in the study group than in the control group at 4.5 to 10.0 seconds after the blinking (p < 0.05). We found significant improvements 2 weeks after treatment not only in TBUT (p < 0.001) but also in the mean OSI, the OSI change rate, and the slope of the linear regression line of the OSI within 10 seconds (p < 0.001, p = 0.003, and p = 0.002, respectively). We also found significant improvements 4 weeks after treatment in these variables. CONCLUSIONS: Intraocular scattering deteriorates significantly with time in patients with short TBUT dry eye. Diquafosol ophthalmic solution exhibits an improvement not only in TBUT but also in intraocular scattering, indicating that diquafosol is also effective for improving the optical quality of the eye.

Effectiveness of a Toothpaste with Low Fluoride Content Combined with Trimetaphosphate on Dental Biofilm and Enamel Demineralization in situ.

OBJECTIVE: The aim of the present study was to evaluate in situ whether a toothpaste with low fluoride associated with sodium trimetaphosphate (TMP) would provide similar effect to that of a 1,100 ppm F toothpaste. DESIGN: This crossover double-blind study consisted of 4 phases (14 days each), during which 10 volunteers wore oral appliances containing 4 enamel bovine blocks. The cariogenic challenge was performed by the application of a 20% sucrose solution (6×/day). The toothpaste treatments (2×/day) were: placebo, 500 ppm F, 500 ppm F plus 1% TMP, and 1,100 ppm F. At the end, enamel mineral loss and biofilm composition were analyzed. RESULTS: The toothpaste with 500 ppm F plus 1% TMP showed the lowest mineral loss (p < 0.05). Regarding the fluoride and calcium concentrations in the enamel and in the biofilm, there were no significant differences between 500 ppm F plus 1% TMP, and 1,100 ppm F toothpastes (p > 0.569), but they were significantly different when compared to toothpaste with 500 ppm F (p < 0.050). CONCLUSION: The addition of 1% TMP to a low-fluoride toothpaste reduces enamel demineralization in situ similar to a 1,100 ppm F toothpaste.

Prominent Decrease of Tear Meniscus Height With Contact Lens Wear and Efficacy of Eye Drop Instillation.

OBJECTIVE: To investigate the change in tear meniscus height (TMH) before and after wearing soft contact lenses (CLs) of different water contents (WCs) and the influence of eye drop instillation on TMH during CL wear. METHODS: Tear meniscus heights were measured using anterior segment optical coherence tomography in 20 normal subjects wearing a high-WC CL (WC, 69%) in 1 eye and a low-WC CL (WC, 24%) in the other. Tear meniscus height change after eye drop instillation with 3% diquafosol ophthalmic solution or saline with CL wear was evaluated at 5, 15, 30, and 60 min after instillation. RESULTS: A significant decrease in TMH was observed after lens insertions of both CLs. Tear meniscus height was significantly decreased with high-WC CL wear compared with that with low-WC CL wear. With high-WC CL wear, TMH increased significantly (P<0.001) at 5 min after the instillation of 3% diquafosol ophthalmic solution compared with the baseline values and then returned to the pre-instillation level. No significant TMH changes were found with the instillation of either eye drop (diquafosol or saline) with low-WC CL wear. CONCLUSIONS: Tear meniscus height decreased with CL wear, especially with high-WC CL wear. Significant increases in TMH were observed at 5 min after the instillation of diquafosol ophthalmic solution with high-WC CL wear. The increases in TMH after diquafosol instillation tended to be greater than those after saline instillation at least for 30 min with both high-WC and low-WC CLs.

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.

The effects of 3% diquafosol sodium application on the tear functions and ocular surface of the Cu,Zn-superoxide dismutase-1 (Sod1)-knockout mice.

PURPOSE: To investigate the role of a water and mucin secretagogue (3% diquafosol sodium eye drops) on the tear function and conjunctival ocular surface changes in Sod1(-/-) in comparison to the wild-type (WT) mice. METHODS: Fourteen eyes of 7 Sod1(-/-) male mice with C57BL/background and 14 eyes of 7 C57BL6 strain wild-type male mice were examined at 40 weeks in this study. All mice had application of 3% diquafosol ophthalmic solution six times a day for 2 weeks. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was performed before and after eye drop instillations. Aqueous tear quantity was measured with phenol red-impregnated cotton threads without anesthesia. Animals were sacrificed at 42 weeks after diquafosol treatment and the whole globe specimens were subjected to periodic acid Schiff staining. Goblet cell density was quantified by J Image software. Quantitative real-time PCR for conjunctival muc 5AC messenger RNA expression was also performed. RESULTS: Sod1(-/-) mice had significantly higher fluorescein staining scores compared to the WT mice before eye drop instillation. The mean tear film breakup time, Rose Bengal staining scores, and muc5 messenger RNA expression improved significantly with diquafosol treatment in both the WT and the knockout mice. The mean fluorescein staining score and aqueous tear quantity significantly improved in the Sod1(-/-) mice with treatment. A notable and consistent increase in goblet cells and decrease in inflammatory cell infiltrates could be confirmed in all specimens after 2 weeks of diquafosol eye drop application. CONCLUSIONS: Three percent diquafosol ophthalmic solution appears to be effective in the treatment of ocular surface disease in this age-related dry eye disease mouse model.

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.

Effects of a Long-Acting Diquafosol Ophthalmic Solution on the Ocular Surface, Tolerability, and Usability in Dry Eye Disease.

INTRODUCTION: This study aimed to investigate the tolerability of high-viscosity diquafosol tetrasodium (DQS) ophthalmic solution (DIQUAS LX; DQSLX) and examine its usability and effect on clinical findings in patients with dry eye disease (DED). METHODS: This interventional retrospective study included 66 eyes of 66 patients with DED who switched from conventional DQS to DQSLX ophthalmic solution. Tear function assessments (tear film breakup time [BUT], keratoconjunctival vital staining [VS] score), evaluations of DED symptom relief, and a four-item usability questionnaire ("comfort upon instillation," "irritation upon instillation," "eye mucus discharge," "convenience of instillation frequency") assessed using a visual analog scale from 0 (worst) to 10 (best) were administered 4 weeks after switching to DQSLX. Factors associated with drug tolerability were assessed using multiple regression analysis. RESULTS: The symptoms improved by 64.2% after switching to DQSLX. The BUT value, VS score, and the questionnaire items "comfort upon instillation" and "convenience of instillation frequency" were significantly improved after switching to DQSLX. DQSLX tolerability was reported as acceptable in 56 (84.8%) and unacceptable in 10 (15.2%) patients. Overall, DQSLX tolerability was significantly associated with "comfort upon instillation" and "convenience of instillation frequency" and tended to be associated with a VS score ≥ 1. DQSLX tolerability depended on symptom and VS score improvements and absence of excessive "eye mucus discharge" in patients with a VS score ≥ 1 (39 patients), but on "comfort upon instillation" and absence of excessive "eye mucus discharge" in patients with a VS score = 0 (27 patients). CONCLUSION: The high-viscosity DQSLX ophthalmic solution was generally considered acceptable in the study population. However, drug tolerability seemingly differed between patients with DED with and without epithelial damage. The former were affected by improvements in symptoms and clinical findings, whereas the latter were affected by comfort upon instillation. TRIAL REGISTRATION: University Hospital Medical Information Network identifier, UMIN000051390.

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.

In vitro evaluation of the effect of mouth rinse with trimetaphosphate on enamel demineralization.

OBJECTIVE: The aim of this study was to investigate the effectiveness of sodium trimetaphosphate (TMP) addition to mouth rinses to inhibit enamel demineralization. DESIGN: Bovine enamel blocks (n = 88) were selected by surface hardness and divided into eight treatment groups (n = 11 per group): placebo, 100 or 225 µg F/ml; the rinses with 100 µg F/ml had differing TMP concentrations (range 0-0.6%). The blocks were subjected to pH cycling for 5 days and treated twice a day with mouth rinses. After that, surface and cross-sectional hardness as well as fluoride in enamel were measured. RESULTS: The groups containing both 100 µg F/ml and 0.4% TMP inhibited demineralization most effectively (p < 0.001). This formulation yielded lower values of lesion areas than the formulations containing 100 or 225 µg F/ml but no TMP. The addition of 0.4% TMP increased the fluoride in enamel. CONCLUSION: It is possible to improve the effectiveness of a mouth rinse with 100 µg F/ml by addition of TMP, this being superior in inhibiting enamel demineralization compared with mouth rinses containing 225 µg F/ml.