Early vs late initiation of sodium glycerophosphate: Impact on hypophosphatemia in preterm infants <32 weeks.

BACKGROUND & AIMS: Early electrolyte and mineral imbalances have emerged as a conspicuous problem in very preterm babies since the revision of nutrition guidelines and the eventual implementation of early aggressive parenteral nutrition (PN). We opted to carry out a study with the introduction of phosphorus as sodium glycerophosphate in PN from the first day onward to reveal the impact on serum phosphorus and calcium levels following the surge in the incidence of hypercalcemia and hypophosphatemia. METHODS: In this single-center, prospective, observational cohort study, inborn babies <32 gestational weeks and <1500 g between August 2017 and July 2018 were enrolled consecutively. Infants born in the first 6-month of this period were initiated PN (Early phosphorus group) containing phosphorus (1 mmol P as sodium glycerophosphate/100 ml PN) immediately after birth, and in the latter six-months, mineral-free standard PN (Control group) was commenced up until 48 h of life. Parenteral nutritional prescriptions of both groups were similar in terms of macro and micronutrient intakes except for early phosphorus, calcium, and sodium. Serum mineral and electrolyte levels were measured on Days 1-3-7 and compared between the groups. The primary outcome was the presence of hypophosphatemia in the first week of life. The secondary outcome was hypercalcemia, preterm morbidity, and mortality. RESULTS: A total of 261 infants were included in this study. There were 130 babies in Early phosphorus group and 131 in control group. Gestational ages (28.79 ± 2.1 vs 28.46 ± 2.2 weeks, respectively) and birth weights (1138 ± 273 vs 1090 ± 274 g, respectively) were similar in the groups. Mean serum phosphorus levels were higher on all days in Early phosphorus group (p < 0.001). Early phosphorus group had a lower incidence of hypophosphatemia on days 1-3 and 7 (p < 0.001). The percentage of hypercalcemic infants was significantly lower in Early phosphorus group on day 3 (p < 0.001). No difference was noted in terms of hypernatremia in the groups. CONCLUSIONS: Adding phosphorus to PN in the first hours of life reduced the frequency of hypophosphatemia and hypercalcemia without any surge in hypernatremia or morbidity. Nutrition guidelines need to be revised accordingly in terms of early mineral/electrolyte supplementation.

Efficacy and safety of a thermosensitive hydrogel for endoscopic submucosal dissection: An in vivo swine study.

Injectable thermo-sensitive chitosan hydrogels have recently been developed for the use of submucosal fluids in endoscopic submucosal dissections (ESD). This study aimed to investigate the efficacy and safety of chitosan hydrogels during ESD. Submucosal fluids were administered as follows: 0.9% normal saline (NS), 0.4% hyaluronic acid (HA) and chitosan/ß-glycerophosphate (CS/GP) hydrogel. Each solution was administered twice into the stomach and colon of a pig, with a total of 72 ESD procedures performed on 12 pigs. The injected volume and procedure-related parameters were recorded and analyzed. ESDs that created ulcers after 7 days were histologically compared. All ESD specimens were resected en bloc. The total injected volumes during ESD of the stomach (NS, 16.09±3.27 vs. HA, 11.17±2.32 vs. CS/GP, 9.44±2.33; p<0.001) and colon (NS, 9.17±1.80 vs. HA, 6.67±1.50 vs. CS/GP, 6.75±1.57; p = 0.001) were significantly different. Hydrogel showed significant differences from normal saline in terms of fluid power (mm2/vol; NS, 35.70±9.00 vs. CS/GP 57.48±20.77; p = 0.001) and consumption rate (vol/min; NS, 2.59±0.86 vs. CS/GP, 1.62±0.65; p = 0.013) in the stomach. Histological examination revealed preserved muscularis propria, although the chitosan hydrogel resulted in a partial inflammatory response, with a hypertrophied submucosal layer. Chitosan hydrogel was found to be superior to normal saline, with an efficacy similar to that of hyaluronic acid. Nonetheless, long-term histological changes should be evaluated before clinical implementation.

An intelligent vancomycin release system for preventing surgical site infections of bone tissues.

Preventing surgical site infections (SSIs) of implants has drawn significant attention in both basic and clinical research. Implants with convenient preparation methods and intelligent drug release capabilities are highly needed to resist bacterial infection. Herein, we designed an intelligent drug-release system, which can be instantly incorporated with implants during the surgical process. The drug-release system involves ß-glycerophosphate (ß-GP) and chitosan (CS) as a thermosensitive hydrogel for instant construction onto implants and hyaluronic acid (HA) as a trigger to release vancomycin hydrochloride (VH) on demand. Tertiary calcium phosphate (TCP) scaffolds (implants) are vacuum-adsorbed in a solution of the intelligent vancomycin-release system (VH-HA-CS/ß-GP), followed by heating for 40 min at 80 °C to form VH-HA-CS/ß-GP@TCP. The drug-release hydrogel intelligently releases vancomycin depending on the concentration of hyaluronidase, which is secreted by Staphylococcus aureus (S. aureus) in infection sites. Furthermore, VH-HA-CS/ß-GP@TCP showed effective antibacterial properties in vitro and in vivo. The VH-HA-CS/ß-GP drug-release system can be conveniently prepared during surgery for intelligently preventing SSIs in bone tissue.

An Injectable Nanocomposite Hydrogel for Potential Application of Vascularization and Tissue Repair.

In this contribution, an injectable hydrogel was developed with chitosan, gelatin, ß-glycerphosphate and Arg-Gly-Asp (RGD) peptide: this hydrogel is liquid in room temperature and rapidly gels at 37 °C; RGD peptide promises better growth microenvironment for various cells, especially endothelial cells (EC), smooth muscle cells (SMC) and mesenchymal stem cells (MSC). Both stromal cell-derived factor-1 (SDF-1) nanoparticle and vascular endothelial growth factor (VEGF) nanoparticles were loaded in the injectable hydrogel to simulate the natural nanoparticles in the extracellular matrix (ECM) to promote angiogenesis. In vitro EC/SMC and MSC/SMC co-culture experiment indicated that the nanocomposite hydrogel accelerated constructing embryonic form of blood vessels, and chick embryo chorioallantoic membrane model demonstrated its ability of improving cells migration and blood vessel regeneration. We injected this nanocomposite hydrogel into rat myocardial infarction (MI) model and the results indicated that the rats heart function recovered better compared control group. We hope this injectable nanocomposite hydrogel may possess wider application in tissue engineering.

Investigation on solution-to-gel characteristic of thermosensitive and mucoadhesive biopolymers for the development of moxifloxacin-loaded sustained release periodontal in situ gels.

The objectives of present research were to develop and characterize thermosensitive and mucoadhesive polymer-based sustained release moxifloxacin in situ gels for the treatment of periodontal diseases. Poloxamer- and chitosan-based in situ gels are in liquid form at room temperature and transform into gel once administered into periodontal pocket due to raise in temperature to 37 °C. Besides solution-to-gel characteristic of polymers, their mucoadhesive nature aids the gel to adhere to mucosa in periodontal pocket for prolonged time and releases the drug in sustained manner. These formulations were prepared using cold method and evaluated for pH, solution-gel temperature, syringeability and viscosity. In vitro drug release studies were conducted using dialysis membrane at 37 °C and 50 rpm. Antimicrobial studies carried out against Aggregatibacter actinomycetemcomitans (A.A.) and Streptococcus mutans (S. Mutans) using agar cup-plate method. The prepared formulations were clear and pH was at 7.01-7.40. The viscosity of formulations was found to be satisfactory. Among the all, formulations comprising of 21% poloxamer 407 and 2% poloxamer 188 (P5) and in combination with 0.5% HPMC (P6) as well as 2% chitosan and 70% ß-glycerophosphate (C6) demonstrated an ideal gelation temperature (33-37 °C) and sustained the drug release for 8 h. Formulations P6 and C6 showed promising antimicrobial efficacy with zone of inhibition of 27 mm for A.A. and 55 mm for S. Mutans. The developed sustained release in situ gel formulations could enhance patient's compliance by reducing the dosing frequency and also act as an alternative treatment to curb periodontitis.

Avoidance of Overt Precipitation and Patient Harm Following Errant Y-Site Administration of Calcium Chloride and Parenteral Nutrition Compounded With Sodium Glycerophosphate.

Calcium phosphate precipitates present 1 of many challenges associated with parenteral nutrition (PN) compounding. Extensive research has led to the establishment of solubility curves to guide practitioners in the prescription and preparation of stable PN. Concurrent dosing of intravenous products via y-site administration with PN can alter the chemical balance of the solution and modify solubility. Medications containing calcium or phosphate should not be administered in the same line as PN, due to the high potential for precipitation. Herein a case is reported from a pediatric cardiac intensive care unit where a physician ordered the administration of calcium chloride. The bedside nurse added the calcium chloride intermittent infusion as a y-site administration with the patient's PN. The patient's PN had been compounded with sodium glycerophosphate, temporarily available in the United States during a sodium phosphate shortage. The patient did not experience any observable adverse effects from the y-site administration with PN. Following this event, the scenario was replicated to investigate any precipitation risk associated with the y-site administration. Additionally, a separate PN solution containing sodium phosphate rather than glycerophosphate was compounded and used in a laboratory setting to demonstrate the potential for harm had the patient's PN been compounded with an inorganic phosphate source. This replication of the error demonstrates the additional safety gained in relation to precipitation risk when PN solutions are compounded with sodium glycerophosphate in place of sodium phosphate.

The miR-182/SORT1 axis regulates vascular smooth muscle cell calcification in vitro and in vivo.

Arterial calcification is a common feature of cardiovascular disease. Sortilin is involved in the development of atherosclerosis, but the specific mechanism is unclear. In this study, we established calcification models in vivo and in vitro by using vitamin D3 and ß-glycerophosphate, respectively. In vivo, the expression of SORT1 was up-regulated and the expression of miR-182 was down-regulated in calcified arterial tissues. Meanwhile there was a negative correlation between SORT1 expression and miR-182 levels. In vitro, downregulating SORT1 expression using shRNA inhibited ß-glycerophosphoric induced vascular smooth muscle cells (VSMCs) calcification. Moreover, reduced sortilin levels followed transfection of miR-182 mimics, whereas there was a significant increase in sortilin levels after transfection of miR-182 inhibitors. A luciferase reporter assay confirmed that SORT1 is the direct target of miR-182. Our study suggests that SORT1 plays a vital role in the development of arterial calcification and is regulated by miR-182.

Alendronate-loaded, biodegradable smart hydrogel: a promising injectable depot formulation for osteoporosis.

Alendronate (ALN) is a BCS III bone resorption inhibitor, with very poor oral bioavailability. Our approach is to develop a minimally invasive thermogelling system for prolonged local delivery of ALN. For this, different chitosan-based thermogels were developed and characterised in terms of gelation time, injectability, pH, viscosity and thermoreversibility. Chitosan/ß-glycerophosphate (CS/ßGP) hydrogel pursued temperature-dependent, thermoreversible gelation behaviour and was thus selected for drug loading. Increasing ALN concentration resulted in hydrogels with lower porosity and higher density. FTIR and DSC proved interaction between ALN, CS with ßGP. CS/ßGP hydrogel ensured controlled ALN release over 45-65 days depending on initial ALN loading. Freeze drying improved the shelf-life stability with minor impact on thermogelling character. In vivo injection of plain and ALN-loaded hydrogel in rats rapidly gelled 15 min post-injection. Based on histological examination, ALN-loaded thermogel showed less inflammatory response, faster proliferation and maturation of granulation tissue relative to plain thermogel. Hydrogels excised 21-days post-injection proved the biocompatibility and biodegradability of the system. The presented chitosan-based thermogel has significant positive attributes for site-specific, time-controlled, intra-articular delivery of ALN.

Growth and Bone Mineralization of Very Preterm Infants at Term Corrected Age in Relation to Different Nutritional Intakes in the Early Postnatal Period.

Preterm infants often have a reduced bone mineral content (BMC) with increased risk of metabolic bone disease. After birth it is difficult to supply calcium (Ca) and phosphorus (P) comparable to the high fetal accretion rate. It is not known whether high supplementation of minerals in the early postnatal period improves growth and bone mineralization. The aim of this study was to evaluate growth and bone mineralization at term corrected age (TCA) in very and extremely preterm infants who received different enteral Ca and P intakes during the first 10 days of life. Infants (n = 109) with birth weights below 1500 g were randomly assigned to one of three groups that differed in the nutritional protocols delivered until day 10: Group A, mother's own milk (MOM) and donor milk (unfortified); Group B, MOM (unfortified) and preterm formula; Group C, MOM (start fortification >50 mL/day) and preterm formula. Due to the earlier commencement of fortification, Group C received higher intakes of calcium and phosphorus and protein (p < 0.001) until day 10. At TCA weight, length, BMC and bone mineral density (BMD), measured by dual-X-ray absorptiometry, were not different between the groups. Nutritional intake of P was positively associated with length (ß; (95% confidence interval (CI): 0.20 (0.001; 0.393); p-value = 0.048), whereas Ca intake was negatively associated with BMC (-1.94 (-2.78; -1.09); p-value < 0.001). A small interaction between Ca and P intake was only found for BMD (0.003 (0.00002; 0.00006); p-value = 0.036). The volume of human milk per kg provided during the first 10 days was positively associated with BMC (ß; (95% CI): 0.013 (0.002; 0.023); p < 0.017). Higher intakes of Ca and P during the first 10 days, as provided in this study, did not improve bone mineralization at term corrected age.

Can babies oral wipes with fluoride and/or calcium glycerophosphate prevent cariogenic demineralization? An in-vitro study.

BACKGROUND: The difficulties in reaching a good level of oral hygiene in young babies can be partly overcome with the use of baby oral wipes, which have been shown to effectively remove plaque from deciduous teeth. The presence of fluoride and calcium in these wipes could also prevent further demineralization of the teeth, as well as promote remineralization. The aim of this study is, therefore, was to analyze the preventive effect of OW containing F and CaGP on cariogenic demineralization in vitro. METHODS: For this, seventy enamel samples were treated with OW soaked in solutions containing different F concentrations (250 ppm; 500 ppm and 1500 ppm) with or not with 0.13% CaGP and distilled water for the control group. The samples were submitted to an 8-day cariogenic pH cycling. The experimental solutions were applied twice per cycle, by immersing a dry inert oral tissue into 4 mL of the solution and rubbing it over the enamel surface. Enamel microhardness was measured initially and after the experimental cycles. Environmental scanning electron microscope was taken to visualize and quantify elements on the enamel surface. RESULTS: No significant difference was observed (P=0.694), but when the groups containing CaGP were compared to the negative control solution, a significant difference was found. CONCLUSIONS: The presence of 0.13% CaGP and fluoride in concentrations greater than 500 ppm were able to provide protection of dental enamel against demineralization.

Does Adding Intravenous Phosphorus to Parenteral Nutrition Has Any Effects on Calcium and Phosphorus Metabolism and Bone Mineral Content in Preterm Neonates?

The use of parenteral nutritional supplementation of phosphorus may lead to exhibit higher plasma phosphate concentrations and less radiological features in premature neonates susceptible to osteopenia. The present study aimed to assess the beneficial effects of adding intravenous phosphorus to total parenteral nutrition (TPN) on calcium and phosphorus metabolism in preterm neonates by measuring bone mineral content. This open-labeled randomized clinical trial was conducted on premature neonates who were hospitalized at NICU. The neonates were randomly assigned to two groups received TPN with intravenous sodium glycerophosphate or Glycophos (1.5 mmol/kg/day) or TPN without sodium glycerophosphate. At the end of the four weeks of treatment, the presence of osteopenia was examined using DEXA Scan. After completing treatment protocols, the group received TPN with intravenous Glycophos had significantly lower serum alkaline phosphatase (360±60 versus 762±71, P<0.001), as well as higher serum calcium to creatinine ratio (1.6±0.3 versus 0.44±0.13, P<0.001) compared to the control group received TPN without Glycophos. Those who received TPN with intravenous Glycophos experienced more increase in bone mineral density than those in control group (0.13±0.01 versus 0.10±0.02, P<0.001). There was no significant difference in serum calcium and serum vitamin D between the case and control groups. Adding intravenous sodium glycerophosphate to TPN in premature neonates can compensate the lack of bone mineral content and help to prevent osteopenia.

The impact of phosphate-balanced crystalloid infusion on acid-base homeostasis (PALANCE study): study protocol for a randomized controlled trial.

BACKGROUND: This study aims to investigate the effects of a modified, balanced crystalloid including phosphate in a perioperative setting in order to maintain a stable electrolyte and acid-base homeostasis in the patient. METHODS/DESIGN: This is a single-centre, open-label, randomized controlled trial involving two parallel groups of female patients comparing a perioperative infusion regime with sodium glycerophosphate and Jonosteril® (treatment group) or Jonosteril® (comparator) alone. The primary endpoint is to maintain a stable concentration of weak acids [A-] according to the Stewart approach of acid-base balance. Secondary endpoints are measurement of serum phosphate levels, other acid-base parameters such as the strong ion difference (SID), the onset and severity of postoperative nausea and vomiting (PONV), electrolyte levels and their excretion in the urine, monitoring of renal function and glycocalyx components, haemodynamics, amounts of catecholamines and other vasopressors used and the safety of the infusion regime. DISCUSSION: Perioperative fluid replacement with the use of currently available crystalloid preparations still fail to maintain a stable acid-base balance and experts agree that common balanced solutions are still not ideal. This study aims to investigate the effectivity and safety of a new crystalloid solution by adding sodium glycerophosphate to a standardized crystalloid preparation in order to maintain a balanced perioperative acid-base homeostasis. TRIAL REGISTRATION: EudraCT number 201002422520 . Registered on 30 November 2010.

A novel bioactive osteogenesis scaffold delivers ascorbic acid, ß-glycerophosphate, and dexamethasone in vivo to promote bone regeneration.

Ascorbic acid, ß-glycerophosphate, and dexamethasone have been used in osteogenesis differentiation medium for in vitro cell culture, nothing is known for delivering these three bioactive compounds in vivo. In this study, we synthesized a novel bioactive scaffold by combining these three compounds with a lysine diisocyanate-based polyurethane. These bioactive compounds were released from the scaffold during the degradation process. The cell culture showed that the sponge-like structure in the scaffold was critical in providing a large surface area to support cell growth and all degradation products of the polymer were non-toxic. This bioactive scaffold enhanced the bone regeneration as evidenced by increasing the expression of three bone-related genes including collagen type I, Runx-2 and osteocalcin in rabbit bone marrow stem cells (BMSCs) in vitro and in vivo. The osteogenesis differentiation of BMSCs cultured in this bioactive scaffold was similar to that in osteogenesis differentiation medium and more extensive in this bioactive scaffold compared to the scaffold without these three bioactive compounds. These results indicated that the scaffold containing three bioactive compounds was a good osteogenesis differentiation promoter to enhance the osteogenesis differentiation and new bone formation in vivo.

A methylcellulose and collagen based temperature responsive hydrogel promotes encapsulated stem cell viability and proliferation in vitro.

With the number of stem cell-based therapies emerging on the increase, the need for novel and efficient delivery technologies to enable therapies to remain in damaged tissue and exert their therapeutic benefit for extended periods, has become a key requirement for their translation. Hydrogels, and in particular, thermoresponsive hydrogels, have the potential to act as such delivery systems. Thermoresponsive hydrogels, which are polymer solutions that transform into a gel upon a temperature increase, have a number of applications in the biomedical field due to their tendency to maintain a liquid state at room temperature, thereby enabling minimally invasive administration and a subsequent ability to form a robust gel upon heating to physiological temperature. However, various hurdles must be overcome to increase the clinical translation of hydrogels as a stem cell delivery system, with barriers including their low tensile strength and their inadequate support of cell viability and attachment. In order to address these issues, a methylcellulose based hydrogel was formulated in combination with collagen and beta glycerophosphate, and key development issues such as injectability and sterilisation processes were examined. The polymer solution underwent thermogelation at ~36 °C as determined by rheological analysis, and when gelled, was sufficiently robust to resist significant disintegration in the presence of phosphate buffered saline (PBS) while concomitantly allowing for diffusion of methylene blue dye solution into the gel. We demonstrate that human mesenchymal stem cells (hMSCs) encapsulated within the gel remained viable and showed raised levels of dsDNA at increasing time points, an indication of cell proliferation. Mechanical testing showed the "injectability", i.e. force required for delivery of the polymer solution through devices such as a syringe, needle or catheter. Sterilisation of the freeze-dried polymer wafer via gamma irradiation showed no adverse effects on the formed hydrogel characteristics. Taken together, these results indicate the potential of this gel as a clinically translatable delivery system for stem cells and therapeutic molecules in vivo.

Preparation and evaluation of chitosan-based nanogels/gels for oral delivery of myricetin.

A novel nanogel/gel based on chitosan (CS) for the oral delivery of myricetin (Myr) was developed and evaluated comprehensively. The particle size of the obtained Myr-loaded CS/ß-glycerol phosphate (ß-GP) nanogels was in the range of 100-300nm. The rheological tests showed that the sol-gel transition happened when the nanogels were exposed to physiological temperatures, and 3D network structures of the gelatinized nanogels (gels) were confirmed by Scanning Electron Microscopy. Myr was released from CS/ß-GP nanogel/gel in acidic buffers via a Fickian mechanism, and this release was simultaneously accompanied by swelling and erosion. Moreover, the nanogel/gel exhibited no cytotoxicity by MTT assay, and the oral bioavailability of Myr in rats was improved with an accelerated absorption rate after Myr was loaded into CS/ß-GP nanogel/gel. In summary, all of the above showed that CS/ß-GP nanogel/gel was an excellent system for orally delivering Myr.

Effects of Gingko biloba extract (EGb 761) on vascular smooth muscle cell calcification induced by ß-glycerophosphate.

OBJECTIVE: To investigate the effects of Gingko biloba extract (EGb 761) on calcification induced by ß-glycerophosphate in rat aortic vascular smooth muscle cells. METHODS: Rat aortic vascular smooth muscle cells were cultured with various concentrations of EGb 761 and ß-glycerophosphate for 7 days. Calcium content in the cells, alkaline phosphatase activity, cell protein content, NF-κB activation, and reactive oxygen species production were assayed, respectively. RESULTS: The calcium depositions of vascular smooth muscle cells of the ß-glycerophosphate group were significantly higher than those of the control group (p < 0.01), and were inhibited by EGb 761 in a concentration-dependent manner (p < 0.05). Data showed ß-glycerophosphate induced the enhanced expression of alkaline phosphatase, up-regulated the NF-κB activity and increased reactive oxygen species production of vascular smooth muscle cells while these decreased when administrated with EGb 761(p < 0.05). CONCLUSIONS: EGb 761 significantly reduced deposition of calcium induced by ß-glycerophosphate in rat aortic vascular smooth muscle cells. It not only reduced the deposition of calcium, but also inhibited osteogenic transdifferentiation, which may be associated with decreasing expression of alkaline phosphatase, down-regulating the NF-κB activity, and reducing reactive oxygen species production of vascular smooth muscle cells, and may have the potential to serve as a role for vascular calcification in clinical situations.

Topical combined application of dexamethasone, vitamin C, and ß-sodium glycerophosphate for healing the extraction socket in rabbits.

An osteogenic inducer (OI) consisting of dexamethasone, vitamin C, and ß-sodium glycerophosphate has the capacity to induce bone formation in vitro. The aim of this study was to assess the efficacy of the application of this OI on extraction socket healing. The bilateral first mandibular premolars were extracted from 75 New Zealand rabbits. Gelatin sponges carrying OI were implanted into the sockets. Sockets undergoing implantation of gelatin sponges alone were also evaluated, as well as non-implantation sockets. Specimens from each group were evaluated radiographically, histologically, and histomorphometrically using haematoxylin-eosin staining. Results showed earlier new bone formation and higher bone quality and quantity in the OI group compared to the other groups, and the differences were significant at 2, 4, 8, and 12 weeks postoperative. The OI significantly reduced the absorption of alveolar bone in terms of height; however, changes in the width were not significantly different between the three groups (P>0.05). The OI was shown to have a positive effect on healing of the tooth extraction sockets, was inexpensive, and was convenient to use during the operational procedure; therefore this could represent a promising implant material for human clinical application.

Injectable thermosensitive chitosan/glycerophosphate-based hydrogels for tissue engineering and drug delivery applications: a review.

Recently, great attention has been paid to in situ gel-forming chitosan/glycerophosphate (CS/Gp) formulation due to its high biocompatibility with incorporated cells and medical agents, biodegradability and sharp thermosensitive gelation. CS/Gp is in liquid state at room temperature and after minimally invasive administration into the desired tissue, it forms a solid-like gel as a response to temperature increase. The overview of various recently patented strategies on injectable delivery systems indicates the significance of this formulation in biomedical applications. This thermosensitive hydrogel has a great potential as scaffold material in tissue engineering, due to its good biocompatibility, minimal immune reaction, high antibacterial nature, good adhesion to cells and the ability to be molded in various geometries. Moreover, CS/Gp hydrogel has been utilized as a smart drug delivery system to increase patient compliance by maintaining the drug level in the therapeutic window for a long time while avoiding the need for frequent injections of the therapeutic agent. This review paper highlights the recent patents and investigations on different formulations of CS/Gp hydrogels as tissue engineering scaffolds and carriers for therapeutic agents. Additionally, the dominant mechanism of sol-gel transition in those systems as well as their physicochemical properties and biocompatibility are discussed in detail.

In situ evaluation of low-fluoride toothpastes associated to calcium glycerophosphate on enamel remineralization.

OBJECTIVES: This study aimed to evaluate the effect of low-fluoride toothpastes with calcium glycerophosphate (CaGP) on enamel remineralization in situ. METHODS: Volunteers (n=10) wore palatal devices holding four bovine enamel blocks. The treatments involved 5 experimental phases of 3 days each according to the following toothpastes: placebo, 500 ppm F (500 NaF), 500 ppm F with 0.25% CaGP (500 NaF CaGP), 500 ppm F with 0.25% CaGP (500 MFP CaGP) and 1100 ppm F (1100; positive control). After this experimental period, the fluoride, calcium, and phosphorus ion concentrations from enamel were determined. Surface and cross-sectional hardness were also performed. Data were analysed by 1-way ANOVA, Student-Newman-Keuls' test and by Pearson's correlation. RESULTS: The addition of 0.25% CaGP improved the remineralization potential of low-fluoride toothpastes and the NaF as source of fluoride yielded the best results (p<0.001) as evidenced by the hardness analysis. The 1100 ppm F toothpaste provided higher presence of fluoride in the enamel after remineralization (p<0.001). The addition of CaGP to the NaF and MFP toothpastes led to similar calcium concentration in the enamel as the observed with the positive control (p=0.054). CONCLUSIONS: Toothpastes with 500 ppm F (NaF or MFP) and CaGP showed similar remineralization potential than 1100 ppm F toothpaste. CLINICAL SIGNIFICANCE: Toothpastes containing 500 ppm F associated to CaGP, with both fluoride source (NaF or MFP), showed a potential of remineralization similar to commercial toothpaste. Although there is a need for confirmation in the clinical setting, these results point to an alternative for improving the risk-benefit relationship between fluorosis and dental caries in small children.

Cyclic phosphatidic acid inhibits alkyl-glycerophosphate-induced downregulation of histone deacetylase 2 expression and suppresses the inflammatory response in human coronary artery endothelial cells.

Activation of the endothelium by alkyl-glycerophosphate (AGP) has been implicated in the development of atherosclerosis. Our previous study suggested that cyclic phosphatidic acid (cPA) inhibits arterial wall remodeling in a rat model in vivo. However, the mechanisms through which specific target genes are regulated during this process remain unclear. Here, we examined whether cPA inhibited AGP-induced expression of class I histone deacetylases (HDACs, namely HDAC1, HDAC2, HDAC3, and HDAC8), which may affect subsequent transcriptional activity of target genes. Our experimental results showed that human coronary artery endothelial cells (HCAECs) expressed high levels of HDAC2 and low levels HDAC1, HDAC3, and HDAC8. Moreover, AGP treatment induced downregulation of HDAC2 expression in HCAECs. However, cotreatment with cPA inhibited this downregulation of HDAC2 expression. Interestingly, treatment with AGP increased the expression and secretion of endogenous interleukin (IL)-6 and IL-8; however, this effect was inhibited when HCAECs were cotreated with cPA or the synthetic peroxisome proliferator-activator receptor gamma (PPARγ) antagonist T0070907. Thus, our data suggested that cPA may have beneficial effects in inflammation-related cardiovascular disease by controlling HDAC2 regulation.