Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats.

Doxorubicin is an effective drug for cancer treatment; however, cardiotoxicity limits its use. Cardiotoxicity pathophysiology is multifactorial. GLP-1 analogues have been shown to reduce oxidative stress and inflammation. In this study, we evaluated the effect of pretreatment with liraglutide on doxorubicin-induced acute cardiotoxicity. A total of 60 male Wistar rats were allocated into four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). L and DL received subcutaneous injection of liraglutide 0.6 mg/kg daily, while C and D received saline for 2 weeks. Afterwards, D and DL received a single intraperitoneal injection of doxorubicin 20 mg/kg; C and L received an injection of saline. Forty-eight hours after doxorubicin administration, the rats were subjected to echocardiogram, isolated heart functional study, and euthanasia. Liraglutide-treated rats ingested significantly less food and gained less body weight than animals that did not receive the drug. Rats lost weight after doxorubicin injection. At echocardiogram and isolated heart study, doxorubicin-treated rats had systolic and diastolic function impairment. Myocardial catalase activity was statistically higher in doxorubicin-treated rats. Myocardial protein expression of tumor necrosis factor alpha (TNF-α), phosphorylated nuclear factor-κB (p-NFκB), troponin T, and B-cell lymphoma 2 (Bcl-2) was significantly lower, and the total NFκB/p-NFκB ratio and TLR-4 higher in doxorubicin-treated rats. Myocardial expression of OPA-1, MFN-2, DRP-1, and topoisomerase 2ß did not differ between groups (p > 0.05). In conclusion, doxorubicin-induced cardiotoxicity is accompanied by decreased Bcl-2 and phosphorylated NFκB and increased catalase activity and TLR-4 expression. Liraglutide failed to improve acute doxorubicin-induced cardiotoxicity in rats.

Microshear bond strength of resin cement to glass-ceramics after intaglio surface staining.

STATEMENT OF PROBLEM: Applying stains to the intaglio surface of computer-aided design and computer-aided manufacturing (CAD-CAM) monolithic ceramic restorations has been proposed as an option to help mask darkened substrates. However, little is known about the effects of this procedure on the adhesion between the resin cement and the ceramic. PURPOSE: The purpose of this in vitro study was to evaluate the effect of intaglio surface staining on the microshear bond strength between 2 CAD-CAM ceramics and a resin cement. MATERIAL AND METHODS: Lithium disilicate (Gmax) and leucite-reinforced (Gpress) ceramic blocks were sectioned, crystalized when indicated, and polished. They received either none, 1, or 2 layers of ceramic stains and a glaze liquid mixture followed by a firing cycle. The surfaces of groups Gmax0, Gmax1, and Gmax2 were etched with 9% hydrofluoric acid etching (HF) for 20 seconds, and those of groups Gpress0 and Gpress1 were etched for 60 seconds. After rinsing and drying, a ceramic primer was applied and air-dried. Resin cement rods (n=24 per group) were built from a silicone mold. Specimens were stored in distilled water for 24 hours before microshear bond testing. Failure mode was observed under a digital microscope. Data were analyzed by using the Kruskal-Wallis and Mann-Whitney nonparametric tests (α=.05). RESULTS: Intaglio staining negatively affected the microshear bond strength for both ceramics. A significant difference was observed between Gmax1 (3.5 ±1.73 MPa) and Gmax2 (3.7 ±2.1 MPa) when compared with Gmax0 (14.2 ±4.4 MPa) and also between GPress0 (25.7 ±5.1 MPa) and Gpress1 (1.8 ±2.7 MPa). No difference was observed between 1 and 2 stain layers for Gmax. Most failures were adhesive for Gmax0, mixed for Gpress, and cohesive within the stain layer for experimental groups. CONCLUSIONS: Intaglio surface staining with a stain and glaze mixture caused a significant reduction in bond strength between resin cement and both ceramics tested.

Silver diamine fluoride and cleaning methods effects on dentin bond strength.

PURPOSE: To assess the effect of silver diamine fluoride (SDF) application on bond strength of current adhesive systems to caries-affected dentin and cleaning procedures to overcome SDF's influence on adhesion to dentin. METHODS: 64 human third molars were randomly divided in eight groups for microshear bond strength testing (MBS). Samples of sound and artificial caries-affected human dentin were treated or not with 38% SDF and restored with an etch-and-rinse or a self-etch bonding system. For the cleaning part, water, aluminum oxide, and pumice paste were used after SDF application to determine whether SDF affected the bond strength to dentin. Fracture mode was evaluated under scanning electron microscope. Data were statistically analyzed by ANOVA. RESULTS: SDF application resulted in the lowest MBS for the self-etching adhesive system on caries-affected dentin (P< 0.05). Cleaning with pumice slurry maintained the MBS in SDF groups when compared to the control groups (not treated with SDF). Fracture evaluation showed more adhesive failures on adhesive systems groups. EDX analysis showed no silver particles when pumice paste was used for cleaning. CLINICAL SIGNIFICANCE: Self-etch adhesive systems do not seem appropriate for bonding SDF-treated dentin restorations. Cleaning SDF-treated dentin with pumice paste reduced the negative effect of SDF on resin-dentin bond strength. Etch-and-rinse adhesive systems seemed not be affected by 38% SDF.

The effect of silver diamine fluoride and cleaning methods on bond strength of glass-ionomer cements to caries-affected dentin.

PURPOSE: To evaluate the effect of silver diamine fluoride (SDF) application on the microshear bond strength (MBS) of glass-ionomer cements (GIC) to caries-affected dentin (Part 1) and dentin cleaning methods to reduce SDF's potential effect on MBS (Part 2). METHODS: For Part 1, 56 extracted human teeth were randomly divided into eight groups with GIC, 38% SDF application and dentin substrate. Samples of artificial caries-affected human dentin were treated or not with 38% SDF and restored with conventional or resin-modified GIC. The same procedures were performed in sound dentin tested for MBS test after 24 hours. In Part 2, different dentin cleaning agents (water, aluminum oxide, and pumice slurry) were tested after SDF application. The procedure was performed on the group that presented the worst values for MBS in Part 1. Fracture mode was evaluated under scanning electron microscope. Data were statistically analyzed by ANOVA. RESULTS: MBS was affected by the presence of caries and the type of material, with the conventional GIC the most affected (P< 0.05). Pumice slurry was superior in comparison to the other agents in cleaning SDF-treated dentin. Fracture evaluation showed more mixed failures in all the groups. CLINICAL SIGNIFICANCE: Clinicians should have caution when selecting the glass-ionomer cement (GIC) for restorations in silver diamine fluoride (SDF)-treated dentin. The mechanical properties of conventional GIC restorations were more affected than resin-modified GICs. Pumice slurry was the most effective cleaning method to minimize the negative effect of SDF on dentin.

Marginal and internal fit of CAD-CAM composite resin and ceramic crowns before and after internal adjustment.

STATEMENT OF PROBLEM: With the development of computer-aided design and computer-aided manufacturing (CAD-CAM) technology, dentists may determine internal spacing by using the CAD-CAM software program and make internal adjustments during the clinical evaluation appointment. How these factors affect marginal adaptation is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the marginal and internal adaptation of CAD-CAM ceramic and composite resin crowns with different internal spacings before and after internal adjustment by using microcomputed tomography. MATERIAL AND METHODS: Eight third molars were prepared for a complete crown, and 32 crowns were milled at chairside from composite resin and ceramic materials with different internal spacing (30 µm and 80 µm). After an initial microcomputed tomography scan, the same crowns were adjusted and scanned again. Axial space, occlusal space (OS), marginal discrepancy, and absolute marginal discrepancy were evaluated in both analyses. The need for internal adjustment was determined by an experienced clinician by using a silicone film. The number of internal adjustments was also recorded. The data were analyzed by using a 3-way ANOVA (material, internal spacing, and internal adjustment) and the Bonferroni correction (α=.05). RESULTS: For axial space, only the material factor was significantly different (P<.001), with the ceramic having the lowest value. For OS, both internal spacing and adjustments presented a statistical difference among groups with the lowest OS values obtained for 80-µm spacing after adjustment. For marginal discrepancy and absolute marginal discrepancy, the adjustment factor also had a significant effect, and the adjustment resulted in smaller measures for both variables. The 30-µm spacing required more adjustments than the 80-µm spacing (P<.05). CONCLUSIONS: Both the internal adaptation and marginal adaptation were influenced by the internal adjustment, resulting in improved values for both. Although no differences were observed between the 30-µm and 80-µm spacings after internal adjustment for marginal adaptation, the 30-µm spacing required twice as many adjustments, resulting in longer clinical sessions.

Marginal and internal fit of CAD-CAM-fabricated composite resin and ceramic crowns scanned by 2 intraoral cameras.

STATEMENT OF PROBLEM: The precision of fit of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) complete crowns is affected by digital impression and restorative material. PURPOSE: The purpose of this in vitro study was to evaluate by microcomputed tomography (µCT) the marginal and internal adaptation of composite resin and ceramic complete crowns fabricated with 2 different intraoral cameras and 2 restorative materials. MATERIAL AND METHODS: Ten extracted human third molars received crown preparations. For each prepared molar, 2 digital impressions were made with different intraoral cameras of the CEREC system, Bluecam and Omnicam. Four groups were formed: LB (Lava Ultimate+Bluecam), EB (Emax+Bluecam), LO (Lava Ultimate+Omnicam), and EO (Emax+Omnicam). Before measuring the precision of fit, all crowns were stabilized with a silicone material. Each unit (crown + prepared tooth) was imaged with µCT, and marginal and internal discrepancies were analyzed. For the 2D analysis, 120 measurements were made of each crown for marginal adaptation, 20 for marginal discrepancy (MD), and 20 for absolute marginal discrepancy (AMD); and for internal adaptation, 40 for axial space (AS) and 40 for occlusal space (OS). After reconstructing the 3D images, the average internal space (AIS) was calculated by dividing the total volume of the internal space by the contact surface. Data were analyzed with 2-way ANOVA and quantile regression. RESULTS: Regarding marginal adaptation, no significant differences were observed among groups. For internal adaptation measured in the 2D evaluation, a significant difference was observed between LO and EO for the AS variable (Mann-Whitney test; P<.008). In assessment of AIS by the 3D reconstruction, LB presented significantly lower values than the other groups (Tukey post hoc test; P<.05). Bluecam presented lower values of AIS than Omnicam, and composite resin crowns showed less discrepancy than did ceramic crowns. CONCLUSIONS: The marginal adaptations assessed in all groups showed values within the clinically accepted range. Moreover, the composite resin blocks associated with the Bluecam intraoral camera demonstrated the best results for AIS compared with those of the other groups.

Periradicular repair after single- and two-visit root canal treatments using ultrasonic irrigant activation and calcium hydroxide dressing of teeth with apical periodontitis: study protocol for randomized controlled trials.

BACKGROUND: In certain clinical situations, root canal treatment in teeth with apical periodontitis is performed in multiple visits, with the use of intracanal dressing between visits, aiming to reduce microorganisms and their by-products of the root canal system prior to filling. However, in recent years, discussions have been growing about the real need for the use of intracanal dressing in these cases. The use of ultrasonic activation of the auxiliary chemical substance has increased the potential for decontamination promoted during the chemomechanical preparation of the root canal. Thus, this study is designed to explore whether the use of intracanal dressing between visits during endodontic treatment favors periradicular repair in teeth with apical periodontitis. METHODS: This is a randomized, prospective, double-blinded, controlled clinical trial designed to evaluate 3 distinct clinical approaches used during endodontic therapy: group 1-root canal treatment in a single visit (RCT-SV); group 2-root canal treatment in two visits with intracanal dressing (RCT-TVWD); and group 3-root canal treatment in two visits without intracanal dressing (RCT-TVWOD). A total of 150 adult patients aged 18 to 60, with at least one tooth diagnosed with asymptomatic apical periodontitis and periradicular lesion (confirmed with a cone beam computed tomography (CBCT)), will be randomized and will undergo one of the types of clinical approaches during endodontic therapy. Patients' postoperative pain levels will also be recorded in periods of 24, 48, and 72 h and 7 days. Subsequently, clinical findings and long-term follow-up evaluations, with periradicular repair, will be performed at 6 and 12 months by intraoral periapical radiograph (IOPAR) and CBCT at the 24-month follow-up. DISCUSSION: This study will evaluate the periradicular repair of mandibular molar teeth with apical periodontitis, providing information about the efficacy, benefits, and safety of performing the endodontic treatment in a single and two visits, with and without the use of calcium hydroxide dressing. All endodontic therapy procedures will be performed under a dental operating microscope and using ultrasonic activation of auxiliary chemical substances. These results may contribute to changes in the clinical approaches adopted during endodontic therapy of teeth with apical periodontitis and reveal the potential of complementary approaches that aim to enhance the decontamination of the root canal system during the preparation stage. TRIAL REGISTRATION: ClinicalTrials.gov NCT05256667. Registered on 24 February 2022.

Anti-Inflammatory Effects of Vitamin E in Response to Candida albicans.

Oral mucositis, inflammation, and ulceration that occur in the oral cavity can manifest in significant pain. A formulation was designed to investigate the potential of vitamin E to ameliorate inflammation resulting from Candida albicans in cell-based systems. Human gingival fibroblasts and THP1 cells were stimulated with heat killed C. albicans and Porphyromonas gingivalis LPS (agonists). Unstimulated cells were included as controls. Cells were also simultaneously treated with a novel denture adhesive formulation that contains vitamin E (antagonist). The experimental conditions included cells exposed to the experimental formulation or the vehicle for 2 h for mRNA extraction and analysis, and cells left for 24 h under those experimental conditions for analysis of protein expression by ELISA. ssAffymetrix expression microarray pathway analyses demonstrated that the tested formulation exhibited a statistically significant (p < 0.05) inhibition of the following key inflammatory pathways: TLR 6, IL-1 signaling (IRAK, A20), NF-kappaB, IL-6 signaling (gp130, JK2 and GRB2), TNF signaling (TNF receptor) and Arachidonic acid metabolism (PLA2). Quantitative PCR array analysis confirmed the downregulation of key inflammatory genes when cells under adhesive treatment were challenged with heat killed C. albicans. PGE2 secretion was inhibited by the tested formulation only on THP1 cells after 24 h stimulation with C. albicans. These results suggest that the active formulation containing vitamin E acetate can modulate inflammatory responses, through anti-inflammatory actions as indicated by in vitro experimental conditions.

Caries assessment spectrum treatment: the severity score.

OBJECTIVES: To appraise the feasibility of the caries assessment spectrum and treatment (CAST) severity score according to the formula (F) recommended in the CAST manual. METHODS: Data from an epidemiological survey of 680 schoolchildren (mean age ± standard deviation: 7.45 ± 0.91 years), living in a low-income area in Brasília, were used. The CAST instrument was used for assessing enamel carious lesions (CAST code = 3), dentine carious lesions (CAST codes = 4-7) and tooth loss from caries (CAST code = 8). RESULTS: The prevalence of carious lesions including enamel and dentine in both deciduous and permanent dentitions was 49.41% and 69.12%, respectively. Calculating the CAST severity score per child using F was unsatisfactory because of the undiscriminating weight given for each CAST code. Modification of weights according to the accepted levels of disease severity for individual CAST codes resulted in a new formula (F1), in which the weight given to cavitated dentine lesions was quadrupled in relation to that given to enamel carious lesions; this was different from F, in which the weight given to such lesions was twofold. F1 was able to categorise satisfactorily the study children into one of three levels of dental caries severity: mild (34.1%); moderate (29.5%); or severe (36.4%). CONCLUSION: According to the outcomes of the present appraisal, it was concluded that the numerical score provided by the CAST severity scores allows an overview of the severity of caries disease and the classification of individuals into mild, moderate or severe levels of dental caries when the new formula (F1) is used.

Methods to evaluate and strategies to improve the biocompatibility of dental materials and operative techniques.

OBJECTIVE: The general aim of this article is to describe the state-of-the-art of biocompatibility testing for dental materials, and present new strategies for improving operative dentistry techniques and the biocompatibility of dental materials as they relate to their interaction with the dentin-pulp complex. METHODS: The literature was reviewed focusing on articles related to biocompatibilty testing, the dentin-pulp complex and new strategies and materials for operative dentistry. For this purpose, the PubMed database as well as 118 articles published in English from 1939 to 2014 were searched. Data concerning types of biological tests and standardization of in vitro and in vivo protocols employed to evaluate the cytotoxicity and biocompatibility of dental materials were also searched from the US Food and Drug Administration (FDA), International Standards Organization (ISO) and American National Standards Institute (ANSI). RESULTS: While there is an ongoing search for feasible strategies in the molecular approach to direct the repair or regeneration of structures that form the oral tissues, it is necessary for professionals to master the clinical therapies available at present. In turn, these techniques must be applied based on knowledge of the morphological and physiological characteristics of the tissues involved, as well as the physical, mechanical and biologic properties of the biomaterials recommended for each specific situation. Thus, particularly within modern esthetic restorative dentistry, the use of minimally invasive operative techniques associated with the use of dental materials with excellent properties and scientifically proved by means of clinical and laboratory studies must be a routine for dentists. This professional and responsible attitude will certainly result in greater possibility of achieving clinical success, benefiting patients and dentists themselves. SIGNIFICANCE: This article provides a general and critical view of the relations that permeate the interaction between dental materials and the dentin-pulp complex, and establish real possibilities and strategies that favor biocompatibility of the present and new products used in Dentistry, which will certainly benefit clinicians and their patients.

Pulp response after application of two resin modified glass ionomer cements (RMGICs) in deep cavities of prepared human teeth.

OBJECTIVES: This study evaluated the human pulp response to the application of two RMGICs in deep cavities in vivo. METHODS: The cavity floor prepared on the buccal surface of 34 premolars was lined with VBP (VBP), Vitrebond (VB) or Dycal® (DY), and restored with composite resin. Additional teeth were used as an intact control group. After 7 or 30-60 days, the teeth were extracted and processed for histological evaluation. The following histological events were scored: inflammatory response, tissue disorganization, reactionary dentin formation and presence of bacteria. RESULTS: At 7 days, VBP and VB elicited a mild inflammatory pulpal response in about 70% of specimens and in 1 specimen for DY. Only 1 specimen of each RMGICs exhibited moderate tissue disorganization. Bacteria and reactionary dentin formation were not found. At 30-60 days, about 20% of specimens lined with RMGICs showed a persistent mild inflammatory pulp response while no inflammatory reaction was observed for DY. Moderate tissue disorganization occurred with both materials. Bacteria were found only in 1 VBP specimen. The mean remaining dentin thickness (RDT) in specimens lined with VBP, VB or DY ranged from 342.3 to 436.1µm, and no statistically significant differences in RDT were found among materials or periods (two-way ANOVA, p>0.05). Comparison of the two RMGICs tested for the histological events at each period showed statistically similar results (Kruskal-Wallis, p>0.05). SIGNIFICANCE: The use of the new Vitrebond formulation (VBP) in deep cavities in vivo caused mild initial pulp damage, which decreased with time, indicating acceptable biocompatibility.

Investigation of the photodynamic effects of curcumin against Candida albicans.

This study describes the association of curcumin with light emitting diode (LED) for the inactivation of Candida albicans. Suspensions of Candida were treated with nine curcumin concentrations and exposed to LED at different fluences. The protocol that showed the best outcomes for Candida inactivation was selected to evaluate the effect of the preirradiation time (PIT) on photodynamic therapy (PDT) effectiveness, the uptake of curcumin by C. albicans cells and the possible involvement of singlet oxygen in the photodynamic action. Curcumin-mediated PDT was also assessed against biofilms. In addition to the microbiological experiments, similar protocols were tested on a macrophage cell line and the effect was evaluated by Methyltetrazolium assay (MTT) and SEM analysis. The optical properties of curcumin were investigated as a function of illumination fluence. When compared with the control group, a statistically significant reduction in C. albicans viability was observed after PDT (P < 0.05), for both planktonic and biofilm cultures. Photodynamic effect was greatly increased with the presence of curcumin in the surrounding media and the PIT of 20 min improved PDT effectiveness against biofilms. Although PDT was phototoxic to macrophages, the therapy was more effective in inactivating the yeast cell than the defense cell. The spectral changes showed a high photobleaching rate of curcumin.