Synthetic resin acid derivatives selectively open the hKV 7.2/7.3 channel and prevent epileptic seizures.

OBJECTIVE: About one third of all patients with epilepsy have pharmacoresistant seizures. Thus there is a need for better pharmacological treatments. The human voltage-gated potassium (hKV ) channel hKV 7.2/7.3 is a validated antiseizure target for compounds that activate this channel. In a previous study we have shown that resin acid derivatives can activate the hKV 7.2/7.3 channel. In this study we investigated if these channel activators have the potential to be developed into a new type of antiseizure drug. Thus we examined their structure-activity relationships and the site of action on the hKV 7.2/7.3 channel, if they have unwanted cardiac and cardiovascular effects, and their potential antiseizure effect. METHODS: Ion channels were expressed in Xenopus oocytes or mammalian cell lines and explored with two-electrode voltage-clamp or automated patch-clamp techniques. Unwanted vascular side effects were investigated with isometric tension recordings. Antiseizure activity was studied in an electrophysiological zebrafish-larvae model. RESULTS: Fourteen resin acid derivatives were tested on hKV 7.2/7.3. The most efficient channel activators were halogenated and had a permanently negatively charged sulfonyl group. The compounds did not bind to the sites of other hKV 7.2/7.3 channel activators, retigabine, or ICA-069673. Instead, they interacted with the most extracellular gating charge of the S4 voltage-sensing helix, and the effects are consistent with an electrostatic mechanism. The compounds altered the voltage dependence of hKV 7.4, but in contrast to retigabine, there were no effects on the maximum conductance. Consistent with these data, the compounds had less smooth muscle-relaxing effect than retigabine. The compounds had almost no effect on the voltage dependence of hKV 11.1, hNaV 1.5, or hCaV 1.2, or on the amplitude of hKV 11.1. Finally, several resin acid derivatives had clear antiseizure effects in a zebrafish-larvae model. SIGNIFICANCE: The described resin acid derivatives hold promise for new antiseizure medications, with reduced risk for adverse effects compared with retigabine.

Calcium hydroxyapatite nanoparticles as a reinforcement filler in dental resin nanocomposite.

The current study focuses on the fabrication of calcium hydroxyapatite (Ca10(PO4)6(OH)2) (HA) in a nanorange having whiskers- and cubic-shaped uniform particle morphology. The synthesized HA particles hold a promising feature as reinforcement fillers in dental acrylic resin composite. They increase the efficacy of reinforcement by length and aspect ratio, uniformity, and monodispersity. Therefore, the acrylic resin was reinforced with the as-synthesized monodispersed HA filler particles (0.2-1 Wt%). The presence of filler particles in the composite had a noticeable effect on the tribological and mechanical properties of the dental material. The morphological effect of HA particles on these properties was also investigated, revealing that cubic-shaped particles showed better results than whiskers. The as-fabricated composite (0.4 Wt%) of the cubic-shaped filler particles showed maximum hardness and improved antiwear/antifriction properties. Particle loading played its part in determining the optimum condition, whereas particle size also influenced the reinforcement efficiency. The current study revealed that particle morphology, particle size, uniformity, etc., of HA fillers, greatly influenced the tribological and mechanical properties of the acrylic resin-based nanocomposite. Improvement in the tribological properties of HA particle-reinforced acrylic resin composites (HA-acrylic resin) followed the trend as AR < CmC < WC < CC.

Monitoring enamel caries on resin-treated occlusal surfaces using quantitative light-induced fluorescence: an in vitro study.

The aim of this study is to evaluate the ability of quantitative light-induced fluorescence (QLF) to monitor enamel caries lesions of different severity stages located on the occlusal surfaces of permanent teeth before and after treatment with resin infiltrant. Sixty extracted permanent teeth had one occlusal site selected and were categorized according to the International Caries Detection and Assessment System (ICDAS) criteria. The teeth were divided into three groups (n = 20): ICDAS 1, ICDAS 2, and ICDAS 3. The teeth were assessed by a trained examiner using QLF in two phases: (A) before and (B) after treatment with resin infiltrant. The caries lesions were evaluated using the following QLF parameters: area (mm2); ΔF, fluorescence loss (%); and ΔQ, fluorescence loss integrated over the lesion area (%*mm2). The resin infiltrant (Icon™) was applied on the occlusal surface following the manufacturer's recommendations. The teeth were then sectioned and prepared for polarized light microscopy analysis. The penetration of resin infiltrant was measured with ImageJ. The groups showed a statistically significant difference in all QLF parameters before and after caries infiltration, with the reduction of fluorescence values posttreatment (p < 0.05). Infiltrant penetration was observed in all groups, with a statistical difference between all groups (p < 0.05). The reduction in QLF parameters after resin infiltration suggests that QLF is able to monitor enamel caries lesions of different severity stages located on the occlusal surfaces of permanent teeth before and after treatment with resin infiltrant.

Cytokine expression in response to root repair agents.

AIM: To evaluate the expression of TNF-α, IL-6, IFN-γ, TGF-ß, IL-4, IL-10, RANKL, RANK and OPG on mouse calvarial bone treated with MTA, Geristore® and Emdogain® . METHODOLOGY: Bone wounds were made on the heads of C57BL/6 mice, breaking the periosteum and the cortical surface of the calvaria. Each repair agent was inserted into sectioned Eppendorf microtubes and placed on the bone wound, and soft tissues were sutured. At 14 and 21 days, animals were sacrificed and the treated region was dissected. The calvaria bone was removed, and RNA was extracted. mRNA expression of the aforementioned cytokines was assessed using real-time PCR. Data were analysed by nonparametric methods, including the Mann-Whitney and Kruskal-Wallis tests (P < 0.05). RESULTS: Following treatment with Emdogain® and MTA, mRNA expression of RANKL, RANK and OPG increased significantly (P < 0.05) between days 14 to 21. Geristore® did not alter the basal expression of these mediators during the same period of evaluation. Whilst treatment with Emdogain® did cause a significant increase in TNF-α mRNA expression between days 14 and 21 (P < 0.05), treatment with MTA did not alter the basal expression of this cytokine at either experimental time point. However, TNF-α mRNA expression was down-regulated significantly at day 21 (P < 0.05) when Geristore® was applied. A significant increase in the mRNA expression of IL-6, TGF-ß, IL-10, IL-4 and IFN-γ was observed with Emdogain® and MTA treatment between days 14 to 21, whereas Geristore® reduced significantly the expression of IL-6, TGF-ß and IL-4 (P < 0.05). CONCLUSION: The clinical indication of these repair agents depends on the root resorption diagnosis. Whilst MTA and Emdogain® induce a pro- and anti-inflammatory response early and late, respectively, Geristore® was not associated with an inflammatory reaction when compared with both repair agents.

The Setting Time of Polyether Impression Materials after Contact with Conventional and Experimental Gingival Margin Displacement Agents.

PURPOSE: The compatibility of chemical gingival margin displacement agents with polyether impression materials has not been determined. The aim of this study was to evaluate the setting time of polyether impression elastomers after contact with conventional and experimental gingival displacement agents. MATERIALS AND METHODS: The study compared the setting time of two polyether impression materials: medium body (Impregum Penta Soft) and light body (Impregum Garant L DuoSoft) after contact with 10 gingival displacement agents, including 5 conventional astringents (10%, 20%, and 25% aluminum chloride, 25% aluminum sulfate, and 15.5% ferric sulfate) and 5 experimental adrenergics (0.1% and 0.01% HCl-epinephrine, 0.05% HCl-tetrahydrozoline, 0.05% HCl-oxymetazoline, and 10% HCl-phenylephrine). As many as 120 specimens (60 light body and 60 medium body) were mixed with 20 µl of each of 10 gingival displacement agents, and the time to achieve maximum viscosity was measured with a viscometer. The setting times of these specimens were compared with the control group of 12 specimens, which were polymerized without contact with the displacement agents. The experiments were performed in two environments: 23°C and 37°C (± 0.1°C). Individual and average polymerization time compatibility indices (PTCI) were calculated. Data were analyzed by 2-way ANOVA (α = 0.05). RESULTS: The evaluated chemical displacement agents from both groups changed the setting time of light- and medium-body PE. The negative individual PTCI values achieved astringent (20% aluminum chloride) with two PE in both temperature environments. The average PTCI values of the experimental displacement agents at laboratory and intraoral temperatures were significantly higher than the conventional agents. CONCLUSIONS: The present findings suggest that experimental retraction agents can be recommended clinically as gingival margin displacement agents with minimal effects on the setting time of medium- and light-body polyether impression materials; however, direct contact of chemical displacement agents and polyether impression materials can be avoided.

THE IMPACT OF THE ACRYLIC MONOMER ON THE MORPHOLOGICAL STRUCTURE OF RAT LINGUAL MUCOSA.

The analysis of publications shows that diverse multiple factors can induce changes in taste sensitivity and the main irritants are the chemicals of different types. However, the study of the effect of the components of dental structural materials on the state of lingual mucosa, in particular, taste sensors, has not been fully elucidated to date. The purpose of the paper was the study of the effect of monomer of the "Ftoraks" base acrylic resin on the state of the rats' lingual mucosa within 2-4 weeks after its impact. The previous paper [5] presents the findings of the study on the impact of the monomer of the "Ftoraks" base acrylic resin on the state of the rats' lingual mucosa in the early period (1 to 7 days) and its subsequent regeneration. The studies have found that the greatest changes in the lingual mucosa occur on day 3 and 7 after the application of monomer, and are of erosive-inflammatory origin. Regeneration of the lingual epithelium is delayed. The studies confirm that the monomer of acrylic resin causes a number of pathological changes in the mucous membrane and muscles of the rat tongue, the nature of which varies depending on the duration of its impact. On day 14 in the lingual mucosa the destructive processes are significantly delayed, substituting for the sclerotic processes in the proper plate and atrophic processes, observed, first of all, in the papillae of the tongue. It is appropriate to assume that such changes in the papillae will lead to violation of the taste reception, first of all, in the areas of lateral surfaces of the body of the tongue and in the root area. At the same time, it should be noted that at the end of the experimental period (on day 28 of the contact of the monomer with the lingual mucosa), in the mucous membrane of the tongue, along with atrophic and sclerotic processes, the destructive changes and inflammatory reaction are evident. We hypothesize that this may indicate about partial recovery of taste sensitivity due to the decrease in the number of gustatory buds, taste papillae of different types and the increase in the period of their regeneration.

Effects of Self-Assembling Peptide P11-4, Fluorides, and Caries Infiltration on Artificial Enamel Caries Lesions in vitro.

The application of a self-assembling peptide on noncavitated caries lesions is supposed to be a feasible approach to facilitate remineralization and mask their unfavorable appearance. However, demineralizing conditions are common in the oral environment, so the aim of this pH-cycling study was to compare recommended and novel treatment methods regarding their ability to hamper demineralization and as a consequence mask artificial enamel caries lesions. Artificial caries lesions were prepared in bovine enamel and randomly allocated to 11 groups (n = 22). Treatments before pH-cycling were as follows: the application of a self-assembling peptide (Curodont™ Repair [C]), a low-viscosity resin (Icon® [I]), 2 fluoride solutions (10,000 ppm F-: Elmex fluid [E] and 43,350 ppm F-: Tiefenfluorid® [T]), and no intervention (N). During pH-cycling (28 days, 6 × 60 min demineralization/day) half of the specimens in each group were brushed (10 s; 2 ×/day) with either fluoride-free (named e.g., C0) or NaF (1,100 ppm F-; e.g., C1) dentifrice slurry. In another subgroup specimens were pH-cycled but not brushed (NNB). Differences in integrated mineral loss (ΔΔZ), lesion depth (ΔLD), and colorimetric values (ΔΔE) were calculated between values after pre-demineralization, surface treatment, and pH-cycling. Specimens of C0, C1, NNB, N0, N1, T0, and E0 showed significantly increased ΔZ and LD values after pH-cycling (p ≤ 0.003; paired t test). C0, C1, NNB, and N0 showed significantly higher changes in ΔΔZ than E1, I0, I1, and T1 (p < 0.001; ANOVA). Significantly reduced colorimetric values could only be observed for I1, I0, E1, and E0 after treatment and after pH-cycling (p ≤ 0.027; paired t test). In conclusion, under the conditions chosen only the application of a low-viscosity resin could mask caries lesions significantly, whereas self-assembling peptides could neither inhibit lesion progression nor mask the lesions considerably.

An investigation into the effect of a resin infiltrant on the micromechanical properties of hypomineralised enamel.

BACKGROUND: Resin infiltration may alter the mechanical properties of enamel hypomineralised lesions (HL); however, variable surface layer (SL) thickness may affect resin penetration. AIMS: To determine the thickness of the SL of HL and to investigate the effect of resin infiltration on the mechanical properties of HL. DESIGN: The thickness of the SL over HL was determined using polarised light microscopy. Etching time using 15% HCl gel to remove the SL of 52 samples was determined. Selected HL and control areas of 21 teeth were infiltrated with Icon® resin infiltrant, and cross-sectional Knoop microhardness (KHN) measurements were recorded before and after resin infiltration. RESULTS: Ninety-six point five per cent of HL had a detectable SL with mean thickness of 58 ± 29 µm. Application of HCl for 120 s produced a mean MIH erosion depth of 58 ± 12 µm. Eleven of 21 samples had evidence of infiltration using visual examination. The infiltrant penetrated some of the HL leading to an increase in KHN (111 ± 75 KHN) which, when compared to adjacent non-infiltrated HL (96 ± 52 KHN), was not statistically significantly different (P = 0.56). CONCLUSIONS: There was marked variation in the SL thickness of HL. Resin infiltration of HL did not increase microhardness significantly.

Effect of colestimide on the concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dizenzofurans, and polychlorinated biphenyls in blood of Yusho patients.

BACKGROUND: Oral colestimide was reported to lower the concentration of PCDDs, PCDFs, and PCB in the blood of humans. A pilot study showed that the arithmetic mean total TEQ concentrations of PCDDs, PCDFs, and PCBs in the blood of subjects after the trial decreased approximately 20 % compared to pre-trial levels, suggesting that colestimide could decrease human dioxin levels. We designed the current clinical trial study based on this information. In this study, we examined whether colestimide could reduce the individual congener concentrations of PCDDs, PCDFs, and PCBs in the blood of Yusho patients. METHODS: Out of the 36 Yusho patients who participated in the clinical trial, 26 patients self-administered colestimide 3 g/day orally for 6 months. The concentrations of PCDDs, PCDFs and PCBs in the blood of 26 Yusho patients before the trial were compared with those after the trial. RESULTS: The arithmetic mean total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the blood of the 26 Yusho patients before and after the clinical trial were 42-303 (mean: 130, median: 120) and 43-283 (mean: 132, median: 118) pg TEQ/g lipid, respectively. The sums of the concentrations of 58 PCB congeners measured in the blood of Yusho patients before and after the trial were 321-2643 (mean: 957, median: 872) and 286-2007 (mean: 975, median: 806) ng/g lipid, respectively, indicating that the concentrations of PCDDs, PCDFs, and PCBs after the trial were almost the same as those before the trial. Among congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs, most congeners of these compounds did not show a statistically significant decrease after the trial. CONCLUSION: Colestimide may not be beneficial in reducing the high blood levels of dioxin-like compounds in Yusho patients.

In vitro study of the antibacterial properties and impact strength of dental acrylic resins modified with a nanomaterial.

STATEMENT OF PROBLEM: The accumulation of bacteria on the surface of dental prostheses can lead to systemic disease. PURPOSE: The purpose of this in vitro study was to evaluate the growth of Staphylococcus aureus and Pseudomonas aeruginosa on the surface of autopolymerizing (AP) and heat-polymerizing (HP) acrylic resins incorporated with nanostructured silver vanadate (ß-AgVO3) and its impact strength. MATERIAL AND METHODS: For each resin, 216 circular specimens (9 × 2 mm) were prepared for microbiologic analysis and 60 rectangular specimens (65 × 10 × 3.3 mm) for mechanical analysis, according to the percentage of ß-AgVO3: 0%, control group; 0.5%; 1%; 2.5%; 5%; and 10%. After a biofilm had formed, the metabolic activity of the bacteria was measured using the XTT reduction assay (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) (n=8), and the number of viable cells was determined by counting colony forming units per milliliter (CFU/mL) (n=8). Confocal laser scanning microscopy (CLSM) was used to complement the analyses (n=2). The mechanical behavior was evaluated by impact strength assays (n=10). Data were analyzed by 2-way ANOVA, followed by the Tukey honestly significant difference (HSD) post hoc test (α=.05). RESULTS: The addition of 5% and 10% ß-AgVO3 significantly decreased the metabolic activity of P. aeruginosa for both resins (P<.05). The HP resin promoted a greater reduction in metabolic activity than the AP resin (P<.05). No difference was found in the metabolic activity of S. aureus according to the XTT (P>.05). The number of CFU/mL for S. aureus and P. aeruginosa decreased significantly when 5% and 10% ß-AgVO3 were added (P<.001). These concentrations significantly reduced the impact strength of the resins (P<.001) because the system was weakened by the presence of clusters of ß-AgVO3. CONCLUSION: The addition of ß-AgVO3 can provide acrylic resins with antibacterial activity but reduces their impact strength. More efficient addition methods should be investigated.

Three-dimensional finite element analysis of anterior two-unit cantilever resin-bonded fixed dental prostheses.

The aim of this study was to evaluate the influence of different framework materials on biomechanical behaviour of anterior two-unit cantilever resin-bonded fixed dental prostheses (RBFDPs). A three-dimensional finite element model of a two-unit cantilever RBFDP replacing a maxillary lateral incisor was created. Five framework materials were evaluated: direct fibre-reinforced composite (FRC-Z250), indirect fibre-reinforced composite (FRC-ES), gold alloy (M), glass ceramic (GC), and zirconia (ZI). Finite element analysis was performed and stress distribution was evaluated. A similar stress pattern, with stress concentrations in the connector area, was observed in RBFDPs for all materials. Maximal principal stress showed a decreasing order: ZI>M>GC>FRC-ES>FRC-Z250. The maximum displacement of RBFDPs was higher for FRC-Z250 and FRC-ES than for M, GC, and ZI. FE analysis depicted differences in location of the maximum stress at the luting cement interface between materials. For FRC-Z250 and FRC-ES, the maximum stress was located in the upper part of the proximal area of the retainer, whereas, for M, GC, and ZI, the maximum stress was located at the cervical outline of the retainer. The present study revealed differences in biomechanical behaviour between all RBFDPs. The general observation was that a RBFDP made of FRC provided a more favourable stress distribution.

Effect of different cleaning regimens on the adhesion of resin to saliva-contaminated ceramics.

PURPOSE: The aim of this study was to evaluate the influence of different cleaning regimens on the microshear bond strength (µSBS) of three different all-ceramic surfaces after saliva contamination. MATERIAL AND METHODS: Cubic ceramic specimens (3 × 3 × 3 mm(3) ) were prepared from three types of ceramics: zirconium dioxide (Z), leucite-reinforced glass ceramic (E), lithium disilicate glass ceramic (EX; n = 12/subgroup). A total of 144 composite resin cylinders (diameter: 1 mm, height: 3 mm) were prepared. Three human-saliva-contaminated surfaces of ceramic specimens were cleaned with either water spray (WS), with 0.5% sodium hypochlorite solution (HC), or with a cleaning paste (CP). Control surface (C) was not contaminated or cleaned. Composite cylinders were bonded to each surface with a resin luting cement. All specimens were stored at 37°C in deionized water until fracture testing. µSBS tests were performed in a universal testing machine (0.5 mm/min), and the results (MPa ± SD) were statistically analyzed (two-way ANOVA, Bonferroni a = 0.05). Fractured surfaces were analyzed to identify the failure types using an optical microscope at 50× magnification. Two representative specimens from all groups were examined with scanning electron microscopy. RESULTS: µSBS test results were significantly affected by the saliva cleaning regimens (p = 0.01) and the ceramic types (p = 0.03). The interaction terms between the ceramic type and saliva cleaning regimen were also significant (p < 0.05). There were no significant differences among the µSBS values (MPa ± SD) for the Z group (C = 17.5 ± 8.8; WS = 16.0 ± 4.9; HC = 17.6 ± 5.8; CP = 16.6 ± 7.5; p > 0.05). In the EX group, C resulted in significantly higher µSBS values (32.6 ± 7.4) than CP (17.4 ± 8.9), WS (15.6 ± 7.3), and HC (14.3 ± 4.5) (p < 0.05); however, C (20.4 ± 7.1) and HC (19.2 ± 7.5) showed higher µSBS values than CP (13.8 ± 4.8) and WS (10.9 ± 5.7) in the E group. Some cohesive failures within the luting resin were observed in the E and EX groups, whereas only adhesive failures were seen in zirconia groups for all surface treatments. CONCLUSIONS: Different ceramic surface cleaning regimens after saliva contamination of the zirconium dioxide revealed µSBS similar to the control group, whereas all surface cleaning regimens tested significantly decreased the bond strength values in the lithium disilicate glass ceramic. The leucite-reinforced glass-ceramic group benefited from 0.5% sodium hypochlorite solution cleaning with increased bond strengths. CLINICAL SIGNIFICANCE: Adhesive cementation of zirconia presents a clinically challenging protocol, and the cementation surface contamination of the zirconia restorations and the inadequate removal of the contaminants increase the risk of failure, as for all ceramic types. This study demonstrated that surface cleaning regimens should be applied according to different ceramic properties.

In vitro comparison of the cytotoxicity and water sorption of two different denture base systems.

PURPOSE: Denture base resins have the potential to cause cytotoxicity in vivo, and the mechanical properties of resins are affected by water sorption. There is a correlation between residual monomer and water sorption. Thus, the purpose of this study was to evaluate water sorption and cytotoxicity of light-activated urethane dimethacrylate (UDMA) denture base resin compared to a conventional heat-activated polymethyl methacrylate (PMMA) resin. MATERIALS AND METHODS: Two denture base resins, heat-activated PMMA (Meliodent) and light-activated UDMA (Eclipse), were used in this study. Cytotoxicity (5 × 1 mm(2) ) and water sorption (1 × 1 mm(2) ) specimens were made following the manufacturers' instructions (n = 10). Cytotoxicity tests of denture base resins were performed according to ISO10993-5:1999, and water sorption was evaluated according to ISO 1567:1997. ANOVA tests were employed for evaluating data (α = 0.05). RESULTS: There was no cytotoxic effect in either the PMMA or UDMA group. In addition, contrary to short-term water storage, a significantly lower water sorption value was shown for UDMA resins compared to PMMA resins in both 3- and 6-month storage periods (p = 0.043 and p = 0.002, respectively). CONCLUSION: The tested denture base materials adhered to the ISO standards for both cytotoxicity and water sorption. The cytotoxicity of the light-activated UDMA resin tested was statistically similar to that of the heat-activated PMMA resin; however, the UDMA resin exhibited decreased water sorption in long-term water storage.

[THE INFLUENCE OF MODERN ORTHOPEDIC CONSTRUCTIONS ON THE CONDITION OF PERIODONTAL TISSUES OF PATIENTS WITH GENERALIZED PERIODONTITIS].

Patients with generalized periodontitis studied the effect of the partial removable denture made from acrylic met and thermoplastic materials on the state of periodontal tissues. The results of clin- ical studies have shown a significant improvement in oral hygiene, positive change in activity indi- cators current generalized periodontitis: patients for whom orthopedic constructions are made of thermoplastic mass, reduce the depth of periodontl pockets, tooth mobility, bleeding and inflamma- tion of the interdental, papillae and the gingival margin.

Bile acid sequestrants: glucose-lowering mechanisms and efficacy in type 2 diabetes.

Bile acids are synthesized in the liver from cholesterol and have traditionally been recognized for their role in absorption of lipids and in cholesterol homeostasis. In recent years, however, bile acids have emerged as metabolic signaling molecules that are involved in the regulation of lipid and glucose metabolism, and possibly energy homeostasis, through activation of the bile acid receptors farnesoid X receptor (FXR) and TGR5. Bile acid sequestrants (BASs) constitute a class of drugs that bind bile acids in the intestine to form a nonabsorbable complex resulting in interruption of the enterohepatic circulation. This increases bile acid synthesis and consequently reduces serum low-density lipoprotein cholesterol. Also, BASs improve glycemic control in patients with type 2 diabetes. Despite a growing understanding of the impact of BASs on glucose metabolism, the mechanisms behind their glucose-lowering effect in patients with type 2 diabetes remain unclear. This article offers a review of the mechanisms behind the glucose-lowering effect of BASs, and the efficacy of BASs in the treatment of type 2 diabetes.

Biocompatibility and cytotoxicity of two novel low-shrinkage dental resin matrices.

BACKGROUND/PURPOSE: To reduce the polymerization shrinkage of dental composite resin, we used two different ratios of toluene 2,4-diisocyanate (TDI) or 1,6-hexamethylene diisocyanate (HDI) as functional side chains of bisphenol A-glycidyl methacrylate (bis-GMA) to synthesize two series of new dental resin matrices. This study evaluated the biocompatibility and cytotoxicity of these two series of new resin matrices. METHODS: Two series of new dental resin matrices with the ratios of TDI or HDI functional side chain to bis-GMA (defined as B group) being 1:4, 1:2, 1:1 and 3:2 (defined as T1/4, T1/2, T1, T3/2, and H1/4, H1/2, H1, H3/2 groups, respectively) were synthesized. Each resin sample was light cured and immersed in the culture medium for 24 hours to make the extract solution. Then, human gingival fibroblasts were cultured in different extract solutions for 72 hours. The cytotoxicities of different resins were evaluated by microtitertetrazolium (MTT) assay, the levels of cell-produced reactive oxygen species (ROS) induced by different extract solutions was measured. RESULTS: Resins of the T1/4 and B groups revealed significantly higher cytotoxicity than resins of other groups. However, resins of the T1 and T3/2 groups exhibited less cytotoxicity. In general, resins of the TDI-modified groups showed equal or less cytotoxicity and induced equal or lower levels of ROS than the corresponding resins of the HDI-modified and B groups. CONCLUSION: Our results showed that the TDI-modified resin matrices containing more functional side chains were less cytotoxic than the corresponding HDI-modified resin matrices. When the ratio of functional side chain to bis-GMA is increased, the stereo hindrance of resin structure is increased, more toxic resin monomers are trapped in the complicated resin structure, and thus the resin matrix reveals less cytotoxicity. The TDI-modified resin matrices exhibit higher stereo hindrance of resin structure and thus show less cytotoxicity than the corresponding HDI-modified resin matrices.

Use of in situ solid-phase adsorption in microbial natural product fermentation development.

It has been half a century since investigators first began experimenting with adding ion exchange resins during the fermentation of microbial natural products. With the development of nonionic polymeric adsorbents in the 1970s, the application of in situ product adsorption in bioprocessing has grown slowly, but steadily. To date, in situ product adsorption strategies have been used in biotransformations, plant cell culture, the production of biofuels, and selected bulk chemicals, such as butanol and lactic acid, as well as in more traditional natural product fermentation within the pharmaceutical industry. Apart from the operational gains in efficiency from the integration of fermentation and primary recovery, the addition of adsorbents during fermentation has repeatedly demonstrated the capacity to significantly increase titers by sequestering the product and preventing or mitigating degradation, feedback inhibition and/or cytotoxic effects. Adoption of in situ product adsorption has been particularly valuable in the early stages of natural product-based drug discovery programs, where quickly and cost-effectively generating multigram quantities of a lead compound can be challenging when using a wild-type strain and fermentation conditions that have not been optimized. While much of the literature involving in situ adsorption describes its application early in the drug development process, this does not imply that the potential for scale-up is limited. To date, commercial-scale processes utilizing in situ product adsorption have reached batch sizes of at least 30,000 l. Here we present examples where in situ product adsorption has been used to improve product titers or alter the ratios among biosynthetically related natural products, examine some of the relevant variables to consider, and discuss the mechanisms by which in situ adsorption may impact the biosynthesis of microbial natural products.

Hypoglycemic effects of colestimide on type 2 diabetic patients with obesity.

Recent studies have shown colestimide, a bile acid-binding resin, to also exert a glucose-lowering effect via amelioration of insulin resistance. To evaluate the effects of colestimide on glucose metabolism and to elucidate the underlying mechanism, we conducted a 6-month, open-label pilot study on 43 type 2 diabetic patients with obesity (BMI ≥ 25). The subjects were randomized to either treatment with colestimide 4g/day (T group, n=23) or continuation of their current therapy (C group, n=20). In the T group patients, mean HbA1c and fasting glucose improved markedly (from 7.71 ± 0.32% to 6.97 ± 0.20%; from 147.4 ± 7.3mg/dL to 127.0 ± 5.0mg/dL, respectively), while obesity-related parameters, i.e. body weight, waist circumference, and visceral fat and subcutaneous fat as determined by umbilical slice abdominal CT, showed no significant changes. Fractionation analyses of serum bile acids revealed significantly increased cholic acids (CA) and decreased chenodeoxycholic acids (CDCA) in the T group patients. However, no correlation was observed between these changes and ΔHbA1c. According to logistic regression analysis, baseline HbA1c was the only variable predicting the decrease of HbA1c (>0.5%) among sex, age, BMI, total cholesterol, ΔCA and ΔCDCA. The index of insulin resistance, i.e. HOMA-R, did not improve, and the index of ß cell function, i.e. HOMA-ß, actually increased significantly. These results suggests that, in obese patients with type 2 diabetes, the mechanism underlying improved glycemic control with colestimide treatment involves enhanced ß cell activity rather than improved insulin resistance.

The denitration pathway of p-nitrophenol in the hydrogen peroxide catalytic oxidation with an Fe(III)-resin catalyst.

The liquid-phase hydrogen peroxide catalytic oxidation of p-nitrophenol was performed with an Fe(III)-resin catalyst. The conversion and mineralization of p-nitrophenol was effectively achieved at mild reaction conditions with the Fe(III)-resin catalyst. It was found that the oxidant concentration, pH, and temperature dominated the degradation rate of p-nitrophenol. The denitration pathway of p-nitrophenol was proposed, in which the concentration of H(2)O(2) and temperature showed strong influence on the conversion of nitrite to nitrate. To study the factors influencing the denitration of p-nitrophenol, a comparable kinetic study was attempted to know the possible denitration pathway of p-nitrophenol. The results of this investigation indicated that denitration was the possible step occurring with the decomposition of p-nitrophenol.

Antibacterial effects of several current orthodontic materials against Streptococcus mutans.

The aim of this study was to examine the antibacterial effect of several current orthodontic materials against a certain oral bacterium. The antibacterial activities of six orthodontic composite resins (Transbond LR, Light Cure Retainer (LCR), Light Bond, System 1+, Kurasper F, Transbond XT adhesive), two orthodontic bonding materials (Transbond XT primer and System 1+ activator) and two glass ionomer cements (GIC) [Multicure Glass Ionomer and Ketac Cem GIC] were evaluated against Streptococcus mutans. The hard materials were put into the Teflon mould. The liquid materials were put on a paper disc. All materials were handled under aseptic conditions and placed on agar culture plates. All plates were incubated at 5% CO2 and 37 degrees C for 48 hours. The bacterial growth inhibition zones including the diameter of the sample were measured in millimetres. As a result of this study, the multicure GIC showed the highest antibacterial effectiveness, but no inhibition zones were noted for ketac cem GIC. The light bond adhesive of the Reliance orthodontic bonding system produced high antibacterial effect against S mutans, while the Reliance composite (LCR) did not show any antibacterial effect (p < 0.05). Both composite and primer of the transbond XT system demonstrated significant antibacterial effect against the test bacterium when compared to transbond LR (p < 0.05). Among the materials tested, kurasper F, Ormco system 1+ and system 1+ activator showed slight or no inhibitory effect against the test bacterium in this study In patients who have relatively high salivary levels of Streptococci mutans before treatment, the multicure GIC, the Reliance light bond adhesive, and transbond XT system which had high level antibacterial properties could be applied.