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Purpose: The purpose of this study was to assess, in vitro, the color stability and bleaching response of three bulk-fill composite resins-Activa™, Tetric®-N-Ceram Bulk-Fill, and Filtek™ One Bulk-Fill???and one conventional composite resin, Filtek™ Z250, after immersion in commonly consumed carbonated beverages and subsequent home bleaching with 15 percent carbamide peroxide. Methods: Ninety-six samples (two- and four-mm thick) of the materials were immersed in malt drink, energy drink, cola, or distilled water for one day, one week, and two months. After two months, samples underwent home bleaching with 15 percent carbamide peroxide gel. Spectrophotometric analysis measured color and whiteness changes pre-immersion, post-immersion, and post-bleaching. Statistical significance was determined using factorial mixed analysis of variance (ANOVA), three-way ANOVA, and Bonferroni post hoc tests (P<0.05). Results: All tested composite resins exhibited unacceptable discoloration (color change greater than 3.3) after two months in carbonated beverages. Filtek™ One Bulk-Fill and Filtek™ Z250 displayed the most significant discoloration, particularly when immersed in the malt drink (P<0.05). In contrast, Activa™ samples reached unacceptable discoloration within just one week in malt and cola drinks. Home bleaching yielded limited whiteness recovery, with Activa™ presenting acceptable whiteness post-bleaching after staining with cola and energy drinks. Conclusions: This study highlights the aesthetic risks of prolonged carbonated beverage consumption and the limitations of the assessed home bleaching technique using 15 percent carbamide peroxide. Enhanced dental education on the dietary effects of some beverages on restorative materials is indicated by these findings.

Objective. The causes of internal posteruptive discoloration of teeth are bleeding, necroses, infections, and endodontic filling materials. The aim of this study was to establish the results of bleaching endodontically treated teeth using walking bleach, in-office, and combined techniques, using 30% carbamide peroxide and 35% hydrogen peroxide, as well as the effect of etiological factors, and the time elapsed after endodontic treatment on the success of bleaching. Materials and Methods. The research involved 30 endodontically treated teeth in healthy patients. Retroalveolar X-rays were taken to check the quality of root canal obturation. Endodontic treatment and obturation were carried out on the discolored non-vital teeth without any previous endodontic treatment. Before bleaching, two millimeters of the filling were removed from the root canal and the very entry into the canal was protected with glass ionomer cement. The teeth were divided into three groups, depending on the bleaching technique: walking bleach technique (10 patients), in-office technique (10 patients), and combined technique (10 patients). The teeth were bleached with 30% carbamide peroxide and 35% hydrogen peroxide. The bleaching procedure was repeated in all the patients three times. The color of all teeth was determined based on the Vita Classic guide before and after bleaching. The Χ2 square and Kruskal−Wallis tests were used to identify differences in teeth bleaching results. Results. A statistically significant difference (p < 0.05) was established between bleaching success and the time elapsed after endodontic treatment. There were no statistically significant differences observed between the bleaching success and etiological factors, bleaching techniques, or bleaching agents. Conclusions. The effectiveness of non-vital tooth bleaching is affected by the time elapsed after endodontic treatment.

Background: Hyperglycaemia is known to result in oxidative stress tissue injury and dysfunction. Interestingly, studies have reported hepatic and renal oxidative stress injury during prediabetes; however, any injury to the myocardium during prediabetes has not been investigated. Hence this study aims to assess changes in the myocardial tissue in an HFHC diet-induced model of prediabetes., Methods: Male Sprague Dawley rats were randomly grouped into non-prediabetes and prediabetes (n = 6 in each group) and consumed a standard rat chow or fed a high-fat-high-carbohydrate diet respectively for a 20-week prediabetes induction period. Post induction, prediabetes was confirmed using the ADA criteria. Aldose reductase, NADH oxidase 1, superoxide dismutase, glutathione peroxide, cardiac troponins were analysed in cardiac tissue homogenate using specific ELISA kits. Lipid peroxidation was estimated by determining the concentration of malondialdehyde in the heart tissue homogenate according to the previously described protocol. Myocardial tissue sections were stained with H&E stain and analysed using Leica microsystem. All data were expressed as means ± SEM. Statistical comparisons were performed with Graph Pad instat Software using the Student's two-sided t-test. Pearson correlation coefficient was calculated to assess the association. Value of p < 0.05 was considered statistically significant., Results: The prediabetes group showed a markedly high oxidative stress as indicated by significantly increased NADH oxidase 1 and malondialdehyde while superoxide dismutase and glutathione peroxide were decreased compared to non-prediabetes group. There was no statistical difference between cardiac troponin I and T in the non-prediabetes and prediabetes groups. Cardiac troponins had a weak positive association with glycated haemoglobin., Conclusion: The findings of this study demonstrate that prediabetes is associated with myocardial injury through oxidative stress. Future studies are to investigate cardiac contractile function and include more cardiac biomarkers., (© 2022. The Author(s).)

Purpose: The aim of this trial was to evaluate bleaching effectiveness, tooth sensitivity and gingival irritation of whitening patients with 10% versus 37% carbamide peroxide (CP)., Methods: Eighty patients were selected by inclusion and exclusion criteria and randomly allocated into two groups (n = 40): 37% CP and 10% CP. In both groups, patients performed whitening for 3 weeks, 4 h/day for 10% group and 30 min/day for 37% group. Color was evaluated with Vita Classical, Vita Bleachedguide 3D Master and Spectrophotometer Easyshade, at baseline, weekly and 30 days after treatment. Absolute risk and intensity of tooth sensitivity (TS) and gingival irritation (GI) were assessed with numeric rating scale (NRS) and a visual analog scale (VAS). Color changes were compared with t-test for independent samples. TS and GI were evaluated with Fisher's exact tests. Mann-Whitney test was used for NRS, and t-tests for VAS (α = 0.05)., Results: The 37% CP group showed faster whitening than 10% group at 1-3 weeks. However, 1 month after conclusion, both groups showed equivalent bleaching (p = 0.06). Regarding sensitivity and gingival irritation, 10% and 37% groups met no significant differences (p > 0.05)., Conclusion: The use of 37% CP 30 min/day showed equivalent results to 10% 4 h/day., Clinical Significance: The use of 37% carbamide peroxide 30 min/day may decrease the time of tray use in at-home protocol for whitening because it presents equivalent results to 10% carbamide peroxide 4 h/day., (© 2020 Wiley Periodicals LLC.)

Purpose: The aim of this study was to determine whether carbamide peroxide is effective in bleaching vital permanent teeth in children., Methods: A literature search was conducted using all keywords relevant to the research subject. The outcome measures were identified as colour change, tooth sensitivity, oral irritation and patient satisfaction. The certainty of evidence for each outcome was assessed using the current GRADE guidelines., Results: Of 115 potentially relevant articles, 112 were excluded, as they did not exclusively involve children, intervention involved additional treatment such as microabrasion or restorative work, or case studies. Patient satisfaction was not assessed in the three articles so no analysis could be made with regards to this outcome. The GRADE assessment showed that all of the three articles demonstrated very low certainty of evidence for the other assessed outcomes. The overall findings from the studies suggest that a 10% carbamide peroxide overnight tray system is effective at bleaching vital permanent teeth in children and associated tooth sensitivity and oral irritation are found to be in a similar range compared to those reported in adult studies. However, due to the very low certainty of the evidence, it is not possible to draw these conclusions., Conclusion: Better quality randomised controlled trials are needed to investigate the indication, short and long term effectiveness and side effects of carbamide teeth in vital permanent teeth in children., (© 2021. European Academy of Paediatric Dentistry.)

Objectives: To provide a narrative review on vital dental whitening chemistry, toxicity and safety, vital dental whitening techniques, whitening systems, potential side effects of whitening and cyclic whitening using products with a range of concentrations and pH values. In addition, new developments and recommendations in the field of vital dental whitening will be presented to help clinicians understand the whitening process, its advantages, limitations, and the impact of whitening concentration and pH on enamel providing guidance in tailoring whitening treatments., Data: Data were gathered using the following keywords: dental whitening, roughness, hardness, sensitivity, hydrogen peroxide, whitening pH, whitening concentration, whitening chemistry, colour, and toxicity., Sources: An electronic search was performed using PubMed and Scopus databases. Bibliographic material from papers reviewed was then used to find other relevant publications., Conclusions: The effectiveness of vital dental whitening depends on many factors, such as the concentration/pH of the whitening agent, application duration, chemical additives, and re-mineralising agents used. Developing new whitening products and technologies such as nano-additives and alternative carrier systems is showing promising results, and might prove efficient in maximising whitening benefits by accelerating the whitening reaction and/or minimising expected reversible/irreversible enamel structural damage., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Malaria volunteer infection studies (VISs) accelerate new drug and vaccine development. In the induced blood-stage malaria (IBSM) model, volunteers are inoculated with erythrocytes infected with Plasmodium falciparum . Observations of elevated liver enzymes in the IBSM model with new chemical entities (NCEs) promoted an analysis of available data. Data were reviewed from eight IBSM studies of seven different NCEs, plus two studies with the registered antimalarial piperaquine conducted between June 2013 and January 2017 at QIMR Berghofer, Brisbane, Australia. Alanine aminotransferase (ALT) was elevated (> 2.5 times the upper limit of normal [×ULN]) in 20/114 (17.5%) participants. Of these, 8.9% (10/114) had moderate increases (> 2.5-5 × ULN), noted in seven studies of six different NCEs ± piperaquine or piperaquine alone, and 8.9% (10/114) had severe elevations (> 5 × ULN), occurring in six studies of six different NCEs ± piperaquine. Aspartate aminotransferase (AST) was elevated (> 2.5 × ULN) in 11.4% (13/114) of participants, across six of the 10 studies. Bilirubin was > 2 × ULN in one participant. Published data from other VIS models, using sporozoite inoculation by systemic administration or mosquito feeding, also showed moderate/severe liver enzyme elevations. In conclusion, liver enzyme elevations in IBSM studies are most likely multifactorial and could be caused by the model conditions, that is, malaria infection/parasite density and/or effective parasite clearance, or by participant-specific risk factors, acetaminophen administration, or direct hepatotoxicity of the test drug. We make recommendations that may mitigate the risk of liver enzyme elevations in future VISs and propose measures to assist their interpretation, should they occur.

There is strong evidence that oxidant molecules from various sources contaminate solutions of parenteral nutrition following interactions between the mixture of nutrients and some of the environmental conditions encountered in clinical practice. The continuous infusion of these organic and nonorganic peroxides provided us with a unique opportunity to study in cells, in vascular and animal models, the mechanisms involved in the deleterious reactions of oxidation in premature infants. Potential clinical impacts of peroxides infused with TPN include: a redox imbalance, vasoactive responses, thrombosis of intravenous catheters, TPN-related hepatobiliary complications, bronchopulmonary dysplasia and mortality. This is a narrative review of published data., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Hydroperoxides of limonene and linalool are potent sensitizers., Objectives: To investigate the prevalence of contact allergy to both hydroperoxides of limonene and hydroperoxides of linalool, to report clinical relevance, and to investigate patient demographics., Methods: A total of 821 patients (35.6% male, mean age 42.4 years ± 17.8 years) were consecutively patch tested with our departmental baseline series and our fragrance series, including hydroperoxides of limonene 0.3% pet. and hydroperoxides of linalool 1.0% pet. The clinical relevance was assessed for all positive reactions., Results: Positive patch test reactions to hydroperoxides of limonene and to hydroperoxides of linalool were observed in 77 patients (9.4%, 95% confidence interval [CI]: 7.4%-11.4%) and in 96 patients (11.7%, 95%CI: 9.5%-13.9%), respectively; 38 of these patients (4.6%, 95%CI: 3.2%-6.0%) reacted to both. Most reactions were considered to be possibly or probably clinically relevant (66.3% and 68.8%, respectively), and a small proportion were deemed to be of certain clinical relevance (18.2% and 19.8%, respectively)., Conclusion: As compared with previous studies, high numbers of positive reactions to both hydroperoxides of limonene and hydroperoxides of linalool were observed, the majority of which were clinically relevant, supporting their inclusion in the European baseline series., (© 2018 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Parenteral nutrition (PN) is associated with bronchopulmonary dysplasia in premature infants. In animals, PN leads to alveolar loss following stimulation of apoptosis by oxidative stress (oxidized redox potential). Peroxides and aldehydes generated in PN can induce hypo-alveolarization. The implication of peroxides, which is reduced by light protection, is demonstrated. The implication of aldehydes from omega-6 fatty acids oxidation is expected. The hypothesis is that composition and light exposure of PN influences bronchopulmonary dysplasia development. Since SMOFLipid (SMOF) contains a lower amount of omega-6 fatty acids than Intralipid (IL), the aim was to compare, the impacts of PN compounded with SMOF or IL, photo-protected or not, on alveolar development., Materials and Methods: Three-day-old Guinea pigs received PN, photo-protected or not, made with SMOF or IL through a jugular vein catheter. After 4 days, lungs were sampled for determinations of redox potential of glutathione, apoptosis (caspase-3, caspase-8, and caspase-9) and alveolarization index (histology: number of intercepts/mm)., Results: Compared with IL, SMOF induces a greater oxidation of redox potential (-200 ± 1 versus [vs] -205 ± 1 mV), apoptosis (caspase-3: 0.27 ± 0.04 vs 0.16 ± 0.02; caspase-9: 0.47 ± 0.03 vs 0.30 ± 0.03), and a lower alveolarization index (27.2 ± 0.8 vs 30.0 ± 0.9). Photo-protection prevented activation of caspase-9 and was statistically without effect on redox potential, caspase-3, and alveolarization index., Conclusion: In our model, SMOF is pro-oxidant and induces hypo-alveolarization following exaggerated apoptosis. These results highlight the need for further studies before introducing SMOFLipid in standard neonatal care., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Peroxide is a strong oxidizing agent and disinfectant frequently used in orthopedic surgery. The authors conducted a systematic literature review of peroxide in orthopedic surgery, evaluating use, complications, efficacy, and appropriate concentrations. One hundred seventy-five reports were identified, with 24 being eligible for analysis. Orthopedic surgeons used peroxide for irrigation and bacterial reduction in various procedures. Complications included cytotoxicity, allergic reactions, suture damage, and inflammation. Use of the standard concentration of 3% peroxide and standard time in situ are without evidence. Laboratory studies suggest that diluted concentrations retain the benefit of bacterial decolonization without increasing the risk for complications. [Orthopedics. 2018; 41(6):e756-e764.]., (Copyright 2018, SLACK Incorporated.)

Background Exposure to mercury (Hg) and the ingestion of peroxidized edible oil represent a health risk. This study evaluated the effects of peroxidized coconut oil (CO) on the liver and kidney of rats treated with Hg. Methods Male albino Wistar rats were administered HgCl2 and CO separately or as a combination for 21 days. The concentrations of glutathione (GSH) and malondialdehyde (MDA), as well as the activities of superoxide dismutase (SOD) and catalase (CAT), which were used as markers of oxidative stress were measured in the liver and kidney homogenates. The activities of gamma glutamyl transferase (γ-GT), lactate dehydrogenase (LDH) as well as the levels of bilirubin and creatinine (CREA) as markers of liver and kidney functions were analyzed in the serum. Results The level of MDA in the kidney and liver homogenates was significantly increased in the HgCl2, CO, and CO+HgCl2 groups when compared to control values (p<0.05). Liver SOD activity and GSH level were increased and CAT activity was decreased, whereas kidney GSH level and SOD activity were decreased and CAT activity was increased in the CO and CO+HgCl2 groups when compared to control values (p<0.05). The increase in CREA and bilirubin levels as well as γ-GT and LDH activities observed in the CO+HgCl2 group when compared to the control values (p<0.05) were associated with pathological changes in both tissues, and were considered to be due to oxidative stress. Conclusions In summary, peroxidized CO and Hg alone or in combination induces oxidative damage in the liver and kidney of rats.

Polyacrylic acid (PAA)-modified titanium peroxide nanoparticles (PAA-TiO x NPs) are promising radiosensitizers. PAA-TiO x NPs were synthesized from commercial TiO 2 nanoparticles that were modified with PAA and functionalized by H 2 O 2 treatment. To realize practical clinical uses for PAA-TiO x NPs, their tissue distribution and acute toxicity were evaluated using healthy mice and mice bearing tumors derived from xenografted MIAPaCa-2 human pancreatic cancer cells. Healthy mice were injected with PAA-TiO x NPs at 25 mg/kg body weight via the tail vein, and tumor-bearing mice were injected either into the tumor locally or via the tail vein. The concentration of PAA-TiO x NPs in major organs was determined over time using inductively coupled-plasma atomic emission spectrometry. After 1 h, 12% of the PAA-TiO x NP dose had accumulated in the tumor, and 2.8% of the dose remained after 1 week. Such high accumulation could be associated with enhanced permeability and retention effects of the tumor, as PAA-TiO x NPs are composed of inorganic particles and polymers, without tumor-targeting molecules. The liver accumulated the largest proportion of the injected nanoparticles, up to 42% in tumor-bearing mice. Blood biochemical parameters were also investigated after intravenous injection of PAA-TiO x NPs in healthy mice. PAA-TiO x NPs invoked a slight change in various liver-related biochemical parameters, but no liver injury was observed over the practical dose range. In the future, PAA-TiO x NPs should be modified to prevent accumulation in the liver and minimize risk to patients., (Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Objective: This randomized clinical trial evaluated the effect of 35% hydrogen peroxide in comparison with 37% carbamide peroxide in a nonvital bleaching technique of "walking bleaching" (four sessions of treatment) on periodontal markers: nuclear factor kappa B-ligand (RANK-L-process of root resorption marker) and interleukin 1β (IL-1β-inflammatory response marker)., Methods and Materials: Fifty volunteers presenting with discoloration of nonvital teeth and endodontic treatment in good condition participated. Fifty teeth were randomly divided into two study groups according to bleaching gel: HP = 35% hydrogen peroxide (n=25) and 37% carbamide peroxide (n=25). Nonvital bleaching was performed with a walking bleaching technique consisting of four sessions of bleach application. Gingival crevicular fluid samples were taken in order to quantify the RANK-L and IL-1β levels by enzyme-linked immunosorbent assay. Samples were obtained from six periodontal sites for each bleached tooth: three vestibular and three palatine (mesial, middle, and distal) at seven time periods: baseline, after each of the four sessions of nonvital bleaching, at one week, and at one month after nonvital bleaching. Tooth color variations were analyzed in each session by VITA Bleachedguide 3D-MASTER (ΔSGU)., Results: Significant increments in the RANK-L and IL-1β levels were detected in each evaluated time compared with baseline ( p<0.05); however, no differences were detected between hydrogen peroxide and carbamide peroxide on increments of the biomarkers studied. The change of color was effective for both nonvital bleaching therapies ( p<0.05)., Conclusions: Nonvital bleaching induced a significant increment in the RANK-L and IL-1β levels in periodontal tissues around bleached, nonvital teeth.

Objective The objective of this study was to evaluate dental sensitivity using visual analogue scale, a Computerized Visual Analogue Scale (CoVAS) and a neurosensory analyzer (TSA II) during at-home bleaching with 10% carbamide peroxide, with and without potassium oxalate. Materials and Methods Power Bleaching 10% containing potassium oxalate was used on one maxillary hemi-arch of the 25 volunteers, and Opalescence 10% was used on the opposite hemi-arch. Bleaching agents were used daily for 3 weeks. Analysis was performed before treatment, 24 hours later, 7, 14, and 21 days after the start of the treatment, and 7 days after its conclusion. The spontaneous tooth sensitivity was evaluated using the visual analogue scale and the sensitivity caused by a continuous 0°C stimulus was analyzed using CoVAS. The cold sensation threshold was also analyzed using the TSA II. The temperatures obtained were statistically analyzed using ANOVA and Tukey's test (α=5%). Results The data obtained with the other methods were also analyzed. 24 hours, 7 and 14 days before the beginning of the treatment, over 20% of the teeth presented spontaneous sensitivity, the normal condition was restored after the end of the treatment. Regarding the cold sensation temperatures, both products sensitized the teeth (p<0.05) and no differences were detected between the products in each period (p>0.05). In addition, when they were compared using CoVAS, Power Bleaching caused the highest levels of sensitivity in all study periods, with the exception of the 14th day of treatment. Conclusion We concluded that the bleaching treatment sensitized the teeth and the product with potassium oxalate was not able to modulate tooth sensitivity.

Objectives A single-blinded, randomized, parallel clinical trial evaluated the use of 37% carbamide peroxide (CP) on bleaching effectiveness and tooth sensitivity reported by patients undergoing in-office tooth bleaching, in comparison with the results of using 35% hydrogen peroxide. Material and Methods Forty patients were allocated to receive two sessions of in-office tooth bleaching using either 35% hydrogen peroxide (HP) or 37% CP. Each patient's sensitivity level was evaluated during and up to 24 h after bleaching. The effectiveness of the bleaching procedures was evaluated with a spectrophotometer one week after each session and 30 days after the last session. The impact of tooth bleaching on the patients' perceptions regarding smile changes, in addition to the bleaching procedures and their results, were also recorded. Absolute and relative sensitivity risks were calculated. Data on sensitivity level were analyzed using the Mann-Whitney or T-test, and data from the color evaluation were subjected to 2-way repeated measures ANOVA. Results The use of CP reduced the risk and level of tooth sensitivity to values close to zero, whereas the difference between the bleaching agents disappeared after 24 h. An increased bleaching effect was observed for HP, mainly due to an improved reduction of redness and yellowness. Participants perceived improved tooth bleaching for HP and reduced sensitivity for CP, but no differences regarding the comfort of the techniques were noted. Conclusions In our study, 37% CP resulted in reduced tooth sensitivity but decreased the tooth bleaching effectiveness. However, both bleaching agents resulted in high levels of patient satisfaction.

Invasive multiple cervical root resorptions after vital tooth bleaching is a rare condition. The aim of this article is to present a case of multiple external cervical root resorptions (ECRR) after a misguided home whitening treatment. A 34 year old male patient presented with slight sensitivity and mobility in several teeth. Despite the manufacturer's recommendations, the patient used a 22% carbamide peroxide-based tooth bleaching gel at home for 4 days consecutively, at night, on the upper and lower arches. Clinical examination revealed gingival swelling, probing depths ranging 5-7 mm on the buccal and proximal surfaces, and grade 2 mobility of the teeth affected by ECRR. Radiographs revealed presence of ECRR in several teeth during initial examination, and development of multiple new lesions 6 months later. The teeth were subsequently extracted. Histological analysis showed multiple dentine lacunae and areas of dentine reparation. The careful use of these products can prevent sequelae such as those reported in this clinical case. As the vital bleaching has a variable success rate, patients should be informed through a consent form of the benefits and risks of tooth bleaching treatment., (© 2017 Australian Dental Association.)

Objectives: To investigate the effectiveness of two home bleaching modalities on whitening of tetracycline-stained teeth (TST)., Methods: A randomized controlled trial on the bleaching effect of 15% carbamide peroxide gel loaded in tray and 6.5% hydrogen peroxide strip in subjects with TST was performed. Eligible subjects were judged independently by two assessors, and randomly assigned into the tray or the strip group. Lightness (L*), redness (a*) and yellowness (b*) were measured with colorimeter at baseline, one, two and three months. Any adverse reaction associated with bleaching were also recorded. Overall colour changes (ΔE) were analysed by one-sample and independent t-test/Wilcoxon test at significance level α=0.05., Result: Twelve and fourteen participants were allocated to the tray and the strip group respectively. Both groups experienced noticeable and significant L*a*b* improvement at the end of the trial in comparison to the baseline (p<0.05). Significant improvement was observed in the first month for the tray group (p<0.05) and in the first two months for the strip group (p<0.05). While greater lightness improvement was observed in the tray group over the strip group in the first month (p=0.02), the reverse was noticed in the second month (p=0.01). There was no difference between two groups at the end of this trial (p<0.05) and no significant adverse reactions were observed., Conclusion: Over a three-month period, 6.0% hydrogen peroxide strip performed equally well as the 15% carbamide peroxide tray delivery system in TST., Clinical Significance: Home bleaching systems produce noticeable tooth whitening effect in subjects with tetracycline-stained teeth., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Administration of artemisinin-based combination therapy (ACT) to infant and young children can be challenging. A formulation with accurate dose and ease of administration will improve adherence and compliance in children. The fixed-dose combination dispersible tablet of arterolane maleate (AM) 37.5 mg and piperaquine phosphate (PQP) 187.5 mg can make dosing convenient in children., Methods: This multicenter (India and Africa), comparative, parallel-group trial enrolled 859 patients aged 6 months to 12 years with Plasmodium falciparum malaria. Patients were randomized in a ratio of 2:1 to AM-PQP (571 patients) once daily and artemether-lumefantrine (AL) (288 patients) twice daily for 3 days and followed for 42 days., Results: The cure rate (ie, polymerase chain reaction-corrected adequate clinical and parasitological response) in the per-protocol population at day 28 was 100.0% and 98.5% (difference, 1.48% [95% confidence interval {CI}, .04%-2.91%]) in the AM-PQP and AL arms, respectively, and 96.0% and 95.8% (difference, 0.14% [95% CI, -2.68% to 2.95%]) in the intention-to-treat (ITT) population. The cure rate was comparable at day 42 in the ITT population (AM-PQP, 94.4% vs AL, 93.1%). The median parasite clearance time was 24 hours in both the arms. The median fever clearance time was 6 hours in AM-PQP and 12 hours in the AL arm. Both the treatments were found to be safe and well tolerated. Overall, safety profile of both the treatments was similar., Conclusions: The efficacy and safety of fixed-dose combination of AM and PQP was comparable to AL for the treatment of uncomplicated P. falciparum malaria in pediatric patients., Clinical Trials Registration: CTRI/2014/07/004764., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Linalool and D-limonene are common fragrance ingredients that readily oxidize on exposure to air. The resulting hydroperoxides of linalool and D-limonene have been shown to have high frequencies of positive patch test reactions in several European and international studies., Objective: The aim of the study was to investigate the prevalence of contact allergy to the hydroperoxides of linalool and D-limonene in a US population., Methods: In this retrospective study, 103 patients with suspected fragrance allergy were patch tested to linalool 10% petrolatum (pet), hydroperoxides of linalool 1% pet, D-limonene 10% pet, and/or the hydroperoxides of D-limonene 0.3% pet between July 9, 2014, and October 25, 2016., Conclusions: In this study, the frequency of positive patch test reactions to the hydroperoxides of linalool is 20% (19/96), and the frequency of positive reactions to the hydroperoxides of D-limonene is 8% (7/90). These high frequencies suggest that patch testing to the hydroperoxides of linalool and limonene should be performed in all patients with suspected fragrance allergy.

Background: Ascorbylperoxide (AscOOH) is a hydrogen peroxide-dependent by-product of ascorbic acid that contaminates parenteral nutrition. In a guinea pig model, it caused oxidized redox potential, increased apoptosis, and decreased alveolarization. AscOOH detoxification is carried out by glutathione peroxidase (GPX). We hypothesize that extremely preterm infants have limited capacity for AscOOH detoxification. Our objective was to determine if there is an association between an early level of urinary AscOOH and later development of bronchopulmonary dysplasia (BPD) or death., Materials and Methods: This prospective cohort study included 51 infants at <29 weeks of gestation. Baseline clinical characteristics and clinical outcomes data were collected. Urine samples were collected on days 3, 5, and 7 of life for urinary AscOOH. Blood samples on day 7 were collected for total plasma glutathione, GPX, and glutathione reductase. χ 2 , Student's t test, Spearman correlation ( r), linear regression (adjusted r 2 ), and repeated-measure analysis of variance were used as appropriate. P < .05 was considered significant., Results: Urinary AscOOH increased over time ( P = .001) and was higher in infants who later developed BPD or died ( P = .037). Compared with adults and full-term infants, total plasma glutathione concentration was low (median, 1.02 µmol/L; 25th-75th percentiles, 0.49-1.76 µmol/L), whereas GPX and glutathione reductase activities were sufficient (3.98 ± 1.25 and 0.36 ± 0.01 nmol/min/mg of protein, respectively)., Conclusion: Extremely preterm infants have low glutathione levels, which limit their capacity to detoxify AscOOH. Higher first-week urinary AscOOH levels are associated with an increased incidence of BPD or death.

Background: At-home bleaching is a technique characterized by the use of carbamide peroxide or hydrogen peroxide as a tooth-whitening agent. However, no data exist regarding systemic safety of this technique. The aim of this study was to investigate the effect of at-home bleaching on serum redox homeostasis., Methods: Twenty-nine healthy volunteers who requested tooth-whitening participated in this study. Specified bleaching trays were fabricated for the maxilla and mandible arches. Each participant was given two syringes containing 9% hydrogen peroxide gel to use for 30 min/night for 14 nights consecutively. To evaluate the redox status, the serum concentrations of malondialdehyde (MDA), total antioxidant capacity (TAC) and pro-oxidant-antioxidant balance (PAB) were measured. Blood samples were obtained in the morning prior to initiation of study and the morning after expiration of the bleaching period. The collected data were analyzed using Student's t-test with 95% confidence interval., Results: Twenty-three subjects completed the study. MDA, PAB and TAC were significantly increased after the bleaching period (P = 0.001, 0.001 and 0.002, respectively)., Conclusions: At-home bleaching revealed the potential to disturb oxidant-antioxidant balance and induce oxidative stress. Its clinical relevance is unfavourable and potential side-effects of at-home bleaching should be considered., (© 2016 Australian Dental Association.)

The use of self-medication, which includes dietary supplements and over-the-counter drugs, is still on the rise, while safety issues are not well addressed yet. This especially holds for combinations. For example, iron supplements and magnesium peroxide both produce adverse effects via the formation of reactive oxygen species (ROS). This prompted us to investigate the effect of the combination of three different iron supplements with magnesium peroxide on ROS formation. Hydroxyl radical formation by the three iron supplements either combined with magnesium peroxide or alone was determined by performing a deoxyribose assay. Free iron content of iron supplements was determined using ferrozine assay. To determine hydrogen peroxide formation by magnesium peroxide, a ferrous thiocyanate assay was performed. Finally, electron spin resonance spectroscopy (ESR) was performed to confirm the formation of hydroxyl radicals. Our results show that magnesium peroxide induces the formation of hydrogen peroxide. All three iron supplements induced the formation of the extremely reactive hydroxyl radical, although the amount of radicals formed by the different supplements differed. It was shown that combining iron supplements with magnesium peroxide increases radical formation. The formation of hydroxyl radicals after the combination was confirmed with ESR. All three iron supplements contained labile iron and induced the formation of hydroxyl radicals. Additionally, magnesium peroxide in water yields hydrogen peroxide, which is converted into hydroxyl radicals by iron. Hence, iron supplements and magnesium peroxide is a hazardous combination and exemplifies that more attention should be given to combinations of products used in self-medication., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

In this article, contact allergy to, and the chemical composition of, tea tree oil (TTO) are reviewed. This essential oil is a popular remedy for many skin diseases, and may be used as neat oil or be present in cosmetics, topical pharmaceuticals and household products. Of all essential oils, TTO has caused most (published) allergic reactions since the first cases were reported in 1991. In routine testing, prevalences of positive patch test reactions have ranged from 0.1% to 3.5%. Nearly 100 allergic patients have been described in case reports and case series. The major constituents of commercial TTO are terpinen-4-ol, γ-terpinene, 1,8-cineole, α-terpinene, α-terpineol, p-cymene, and α-pinene. Fresh TTO is a weak to moderate sensitizer, but oxidation increases its allergenic potency. The major sensitizers appear to be ascaridole, terpinolene, α-terpinene, 1,2,4-trihydroxymenthane, α-phellandrene, and limonene. The clinical picture of allergic contact dermatitis caused by TTO depends on the products used. Most reactions are caused by the application of pure oil; cosmetics are the culprits in a minority of cases. Patch testing may be performed with 5% oxidized TTO. Co-reactivity to turpentine oil is frequent, and there is an overrepresentation of reactions to fragrance mix I, Myroxylon pereirae, colophonium, and other essential oils., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Statement of Problem: The influence of different compositions of desensitizing agents in whitening gels should be evaluated., Purpose: The purpose of this clinical trial was to compare the effectiveness of 4 carbamide peroxide (CP)-based bleaching gels containing desensitizing agents regarding the degree of bleaching, tooth sensitivity, degree of participant satisfaction, and gingival irritation., Material and Methods: The maxillary arch of the 50 participants was bleached using a split mouth, home-bleaching technique. The participants were divided into 2 groups: G1, 10% CP (Opalescence PF; Ultradent Products, Inc) (right) and 10% CP (Power Bleaching 10%; BM4) (left); and G2, 15% CP (Opalescence PF) (right) and 16% CP (Power Bleaching 16%) (left). Each gel was used in a 2-hour daily regimen for 45 days. The shade of the 6 maxillary anterior teeth was recorded with a shade guide and spectrophotometer at baseline, and after 15, 30, 45, and 180 days of treatment. Statistical differences were analyzed with ANOVA for repeated measures followed by the Bonferroni and Student t tests (α=.05). Tooth sensitivity was evaluated with a visual analog scale (rated on a 0 to 10 scale). Participant satisfaction was evaluated by using participant reports of their personal satisfaction or dissatisfaction with the shade. Gingival irritation was evaluated using the Löe index scores., Results: Color change was found to be statistically significant for all treatment periods evaluated, both by the objective and the subjective analyses, regardless of the composition and the concentration of the bleaching agent (P<.001). After 45 days, all participants were satisfied with the shade obtained. No clinically diagnosed gingival irritation was noted. Neither of the 10% CP products caused sensitivity during treatment, and 16% CP containing 3% potassium oxalate showed lower sensitivity than 15% CP containing potassium nitrate., Conclusion: The association of 3% potassium oxalate with fluoride was effective in reducing tooth sensitivity during and after bleaching, particularly with the 16% CP product, and did not compromise the effectiveness of treatment., (Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria., Methods: Patients aged 13-65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days., Results: In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100% (140/140) in the FDC of arterolane maleate and PQP group, and 99.3% (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9% (154/159) in the FDC of arterolane maleate and PQP group and 98.7 % (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 % in both the groups (95% CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4% in the FDC of arterolane maleate and PQP group and 85.4% in the chloroquine group. Most of the adverse events were mild to moderate in intensity. The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting (5.0 vs 5.1%), headache (1.3 vs 3.2%) and prolonged QT (1.9 vs 3.2%). No deaths were reported. The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h., Conclusions: The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28. Both the groups showed similar safety profile. Trial Registration Clinical Trial Registry India: CTRI/2011/11/002129.

Objectives: The study aims to compare the efficacy and safety of over-the-counter whitestrips with the American Dental Association (ADA)-recommended home-whitening using the 10 % carbamide peroxide gel., Materials and Methods: Randomized controlled trials (RCTs) comparing the clinical efficacy and safety of the whitestrips with the 10 % carbamide peroxide (10 % CP) gel applied on tray for tooth whitening in adults were searched at PubMed and Cochrane Central Register of Controlled Trials databases and selected up to October 2014. Efficacy of the whitening techniques was assessed through ∆E, ∆L, and ∆b parameters, while side effects were analyzed as dichotomous variables. Data was extracted independently by two reviewers. Metanalysis was performed using random- and fixed-effect models (RevMan 5.3)., Results: Eight studies were included in the metanalysis. The metanalysis revealed no significant difference between the intervention groups for tooth-whitening efficacy measured as ΔE (mean difference [MD]-0.53; 95 % CI [-1.72;0.66]; Z = 0.88; p = 0.38) and ΔL (MD-0.22; 95 % CI [-0.81;0.36]; z = 0.75; p = 0.45); reduction of yellowing was higher with the whitestrips (MD-0.47; 95 % CI [-0.89; -0.06]; Z = 2.25; p = 0.02). Tooth sensitivity (risk ratio [RR] 1.17; 95 % CI [0.81-1.69]; Z = 0.81; p = 0.42) and gingival sensitivity (RR 0.76; 95 % CI [0.53-1.10]; Z = 1.44; p = 0.15) were similar, regardless of the whitening method used. The observed gingival irritation was higher when the 10 % CP gel was applied on tray (RR 0.43; 95 % CI [0.20-0.93]; Z = 2.14; p = 0.03). The quality of evidence generated was rated very low for all outcomes., Conclusions: There is no sound evidence to support the use of the whitening strips in detriment of the ADA-recommended technique based on the 10 % carbamide peroxide gel applied on tray., Clinical Relevance: To the moment, there is no sound evidence in dental literature to suggest that the ADA-recommended whitening technique based on 10 % carbamide peroxide gel could be substituted by the whitening strips. The existing studies, with their limitations, revealed similar tooth whitening and tooth and gingival sensitivity for both whitening techniques.

Tooth bleaching (whitening) is one of the most common and inexpensive method for treating discolouration of teeth. Dental aesthetics, especially tooth colour, is of great importance to majority of the people; and discolouration of even a single tooth can negatively influence the quality of life. Therefore, a review of the literature was carried out (limited to aesthetic tooth-bleaching) to provide a broad overview of the efficacy and adverse effects of various tooth whitening products on soft and hard oral tissues.

Background: The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years., Methods: Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph., Results: A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study., Conclusion: The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and safety results observed in children warrants further studies on FDC of arterolane maleate and PQP dispersible tablets., Trial Registration: Clinical Trial Registry India: CTRI/2009/091/000531.

Aims: The aim was to investigate the QT effect of a single dose combination regimen of piperaquine phosphate (PQP) and a novel aromatic trioxolane, OZ439, for malaria treatment., Methods: Exposure-response (ER) analysis was performed on data from a placebo-controlled, single dose, study with OZ439 and PQP. Fifty-nine healthy subjects aged 18 to 55 years received OZ439 alone or placebo in a first period, followed by OZ439 plus PQP or matching placebos in period 2. OZ439 and PQP doses ranged from 100-800 mg and 160-1440 mg, respectively. Twelve-lead ECG tracings and PK samples were collected serially pre- and post-dosing., Results: A significant relation between plasma concentrations and placebo-corrected change from baseline QTc F (ΔΔQTc F) was demonstrated for piperaquine, but not for OZ439, with a mean slope of 0.047 ms per ng ml(-1) (90% CI 0.038, 0.057). Using an ER model that accounts for plasma concentrations of both piperaquine and OZ439, a largest mean QTc F effect of 14 ms (90% CI 10, 18 ms) and 18 ms (90% CI 14, 22 ms) was predicted at expected plasma concentrations of a single dose 800 mg OZ439 combined with PQP 960 mg (188 ng ml(-1) ) and 1440 mg (281 ng ml(-1) ), respectively, administered in the fasted state., Conclusions: Piperaquine prolongs the QTc interval in a concentration-dependent way. A single dose regimen combining 800 mg OZ439 with 960 mg or 1440 mg PQP is expected to result in lower peak piperaquine plasma concentrations compared with available 3 day PQP-artemisinin combinations and can therefore be predicted to cause less QTc prolongation., (© 2015 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)

The monoterpene ascaridole, a fairly stable endoperoxide found in essential oils such as tea tree oil can provoke allergic contact dermatitis which has been evidenced under patch test conditions. However, concomitantly we observed irritative skin reactions that demand further data underlining the sensitization potential of ascaridole. Here, we studied the effects of ascaridole on dendritic cell (DC) activation and protein reactivity, 2 key steps of chemical-induced skin sensitization. Treatment of human monocyte-derived DC with ascaridole found support for full DC maturation, a capability of sensitizers but not irritants. It induced significant upregulation of the expression of the costimulatory molecules CD86, CD80, CD40, and the adhesion molecule CD54 in a time-dependent manner. Maturation was accompanied by release of proinflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, and IL-8. Similar to other chemical skin sensitizers including hydroperoxides, we observed a certain reactivity of ascaridole toward cysteine- but not lysine-containing peptides. During recent years, evidence accumulated for a radical mechanism as trigger for protein reactivity of peroxides. Treatment of the fairly stable endoperoxide ascaridole with iron as radical inducer ("activated ascaridole") resulted in cysteine peptide reactivity exceeding by far that of ascaridole itself. Furthermore, activated ascaridole showed increased potential for induction of the Nrf2 target gene heme oxygenase 1 and upregulation of CD86 and CD54 on THP-1 cells, an established DC surrogate. These results indicate that radical formation could be involved in the steps leading to skin sensitization induced by the endoperoxide ascaridole., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The purpose of this overview was to review the available literature to determine if there was any evidence that the application of 10% and 15% carbamide peroxide in tooth whitening procedures resulted in tooth (dentine) sensitivity. The conclusions from the review would indicate that tooth whitening with either 10% or 15% carbamide peroxide is an effective and safe treatment when under a dental professionals' supervision. Reported side-effects were considered mild to moderate in nature and were transient in duration. Reported incidences of dentine sensitivity range from 15-65% of patients using 10% carbamide peroxide.

Aim: This study aimed to compare the effect of extended margin and conventional bleaching trays on tooth bleaching and tooth sensitivity. METHOD AND METHODS: Twenty subjects (18-56 years) were investigated in a split arch design clinical study that was conducted in a general dental practice. Each subject received a custom made bleaching tray and 10% carbamide peroxide gel. The bleaching trays had the borders extended 5 mm beyond the gingival margins on the right side and finished just at the gingival margin on the left side. Shade change and tooth sensitivity were the primary outcomes studied and analysed in this study. The shade of the six upper and lower anterior teeth was assessed using a value-ordered shade guide before, one week and two weeks after treatment. Sensitivity was self-assessed using a visual analogue scale (VAS) at the end of the first and second weeks of the study., Results: At the end of week two, the mean shade change was 5.01 (± 3.37) and 5.10 (± 3.36) for teeth covered by extended and non-extended tray design, respectively. The mean VAS sensitivity scores for teeth covered by extended and non-extended tray design were 0.96 (± 1.39) and 0.66 (± 0.96), respectively. There was no significant statistical difference between the two designs at any assessment point with regard to shade change and sensitivity (p >0.05)., Conclusions: It can be concluded that an extended tray design confers no superior effect in terms of the whitening outcome achieved or in reducing levels of sensitivity. Thus, both tray designs can be used depending on a dentist's personal preference.

Dental bleaching has become one of the most frequently requested esthetic treatments in dental offices. Despite the high clinical success observed with this procedure, some adverse effects have been reported, including a potential for developing premalignant lesions, root resorption and tooth sensitivity, especially when misused. The aim of this study was to evaluate the genotoxic response using a micronucleus (MN) assay, after the application of two concentrations of carbamide peroxide. Thirty-seven patients were divided into two groups and randomly received either a 10% carbamide peroxide (CP) (19) or a 16% carbamide peroxide (18) concentration for 21 days in individual dental trays. Gingival margin cells were collected immediately before the first use (baseline), and then 15 and 45 days after baseline. The cells were placed on a histological slide, stained by the Feulgen technique, and evaluated by an experienced blinded examiner. One thousand cells per slide were counted, and the MN rate was determined. The two groups were analyzed by the Wilcoxon rank-sum test and the Kruskal-Wallis equality-of-populations rank test. A slight increase in MN was observed for both groups, in comparison with the baseline, at 15 days. However, no difference was observed between the two groups (10% and 16%), at either 15 or 45 days (p = 0.90). When bleaching is not prolonged or not performed very frequently, bleaching agents containing carbamide peroxide alone will not cause mutagenic stress on gingival epithelial cells.

Arterolane (RBx11160, OZ277) maleate is a rapidly acting synthetic trioxolane anti-malarial. This randomized, placebo controlled study was a phase I study to evaluate the clinical safety and tolerability as well as pharmacokinetics (PKs) of arterolane maleate including food effect. Eight single rising oral doses of arterolane (25, 50, 100, 150, 200, 300, 400, 600 mg), food effect under fed and fasting conditions at 100 mg dose and four multiple oral dose regimens (25, 50, 100, 200 mg) were administered once daily for 7 days in 64 healthy young males (Caucasian). A randomized, placebo-controlled study was also conducted in healthy elderly males and females (Caucasian) to investigate PKs, safety and tolerability of single oral dose (100 mg) of arterolane. All doses were well tolerated after oral administration. The initial peak of arterolane was apparent at 2-3 hours post-dose followed by a secondary peak at approximately 5 hours post-dose. Thereafter, plasma arterolane concentration declined with a geometric mean t1/2 of approximately 2-4 hours. The PKs of arterolane appeared to be time-invariant after repeated once-daily dosing. The incidence of adverse events was similar for placebo and active treatments. Arterolane had similar PKs and tolerability in elderly and younger subjects and between elderly males and females., (© 2013, The American College of Clinical Pharmacology.)

The purpose of this study was to analyze the influence of 10% sodium ascorbate (SA) on the hybrid layer, resin tag length, and bond strength to dentin after bleaching. Six groups were tested: G C, control; G SA, sodium ascorbate (SA) + restoration; G CP, bleaching with carbamide peroxide (CP) + restoration; G CP+SA, bleaching with CP + SA+ restoration; G HP, bleaching with 35% hydrogen peroxide (HP) + restoration; and G HP+SA, HP + SA + restoration. After dental bleaching, the dentin was exposed and the antioxidant solution was applied to groups G SA, G CP+SA, and G HP+SA, before bonding procedures. The teeth were sectioned in the mesiodistal direction. One section was decalcified, and the specimens were embedded in paraffin and sectioned in the longitudinal direction with a thickness of 6 μm. Fifteen slices of each specimen were selected according to a systematic sample of slices with an interval proportional to the total number of slices obtained for each tooth. The specimens were stained using the Brown & Brenn method, and an optic microscope was used to analyze the hybrid layer thickness and resin tag length. The remaining tooth segment was sectioned into stick-shaped specimens and used for microtensile bond strength testing (0.5 mm/min). Statistical analysis was performed using two-way analysis of variance and Fisher test. The results for hybrid layer + tag formation (in micrometers) were G C, 13.27 Aa; G SA, 11.85 Ba; G CP, 6.84 Bb; G CP+SA, 9.02 Ab; G HP, 7.28 Bb; and G HP+SA, 9.22 Ab; bond strength results (in MPa) were G C, 49.5 Aa; G SA, 51.7 Aa; G CP, 37.16 Bb; G CP+SA, 47.69 Aa; G HP, 32.39 Ab; and G HP+SA, 39.67 Ab. Tooth bleaching with CP or HP impairs the formation of the hybrid layer and resin tags and reduces the microtensile bond strength. Statistically, the use of SA significantly increases the hybrid layer thickness and resin tag length. The microtensile bond strength values for carbamide peroxide increased, but the microtensile bond strength for hydrogen peroxide was not affected.

Objective: This randomized clinical trial evaluated the efficacy and safety of four gels of differing concentrations used for at-home vital bleaching., Materials and Methods: Ninety-six volunteers participated in the study and were divided into four groups of 24 individuals. A gel of differing concentration was used for each group: 10% and 15% carbamide peroxide and 7.5% and 9.5% hydrogen peroxide. The patients used the whitening agent in a tray without reservoirs for one hour per day for two weeks. The measurement of the change in tooth color was made by two observers in the maxillary right central incisor and with a colorimeter in both upper central incisors and canines, using the CIE L*a*b* and CIE L*C*h* values. Sensitivity was evaluated by the participants on a scale with values as follows: 0 = absent, 1 = minor, 2 = moderate, 3 = considerable, 4 = severe., Results: At the baseline, the observers noted darker colors than the colorimeter (p<0.01), and there were differences between incisors and canines in all the CIE L*a*b* and CIE L*C*h* values (p<0.001). In all of the groups and for all of the CIE L*a*b* and CIE L*C*h* parameters, there were color changes in the assessments made in the four maxillary teeth after treatment (p<0.001). There were no differences in ΔL* and ΔE* between the groups. The number of patients who experienced sensitivity and the intensity of the sensitivity were not significant., Conclusions: There were no differences in the degree of whitening among the different products. With all of the products there was an increase in L*, a decrease in chromatic intensity (C*), and an increase in the value (tone) or hue (h*).

The aim of this study was to compare the effect of a 16% carbamide peroxide (CP) gel and a 10% CP gel on mineralized enamel content and morphology. Enamel blocks from bovine incisors were subjected to a 14-day treatment (8 h/day) with 10% or 16% CP gels. Knoop microhardness was evaluated before bleaching and at 1, 7 or 14 days after this treatment (50 g/15 s). Mineral content (energy-dispersive x-ray spectroscopy), surface roughness and topography (atomic force microscopy) were evaluated at the 14-day period. Data were analyzed statistically by two-way ANOVA and Tukey's test (α=0.05). Significant microhardness reduction was observed at the 7 th and 14 th days for 10% CP gel, and for all bleaching times for 16% CP gel (p<0.05). At the 14-day period, a significant decrease in Ca and P content, increase on surface roughness (p<0.05) as well as on picks and valleys distance were observed when both bleaching gels were used. These enamel alterations were more intense for 16% CP gel. It was concluded that both CP-based gels promoted loss of mineral structure from enamel, resulting in a rough and porous surface. However, 16% CP gel caused the most intense adverse effects on enamel.

The objective of this study was to evaluate the antioxidant effect of green tea on microtensile bond strength (μTBS) to bleached enamel. Forty-two human third molars were randomly divided into six experimental groups (n = 7 each group): group 1, no treatment; group 2, bleaching (10% carbamide peroxide); group 3, bleaching + 10% sodium ascorbate gel (SA); group 4, bleaching + 10% green tea gel (GT); group 5, SA; and group 6, GT. In groups 2, 3, and 4, bleach was applied onto the enamel surface for 6 h, every day for 14 d. In groups 3 and 5, SA was applied for 1 h; and in groups 4 and 6, GT was applied for 1 h. Immediately after treatment, the specimens were bonded with Adper Single Bond 2 and Filtek Z350 XT. The μTBS of the specimens was tested using a universal testing machine. Fracture mode analysis of the bonded enamel surface was performed using scanning electron microscopy. The mean μTBS values for each group were: group 1, 33.2 ± 5.8 MPa; group 2, 22.6 ± 5.5 MPa; group 3, 30.0 ± 5.2 MPa; group 4, 31.6 ± 3.8 MPa; group 5, 29.1 ± 4.2 MPa; and group 6, 32.2 ± 4.5 MPa. All groups had a higher percentage of mixed failures. In conclusion, green tea can be used as an alternative antioxidant on bleached enamel before bonding procedures., (© 2013 Eur J Oral Sci.)

In-office tooth whitening using hydrogen peroxide (H₂O₂) has been practised in dentistry without significant safety concerns for more than a century. While few disputes exist regarding the efficacy of peroxide-based at-home whitening since its first introduction in 1989, its safety has been the cause of controversy and concern. This article reviews and discusses safety issues of tooth whitening using peroxide-based materials, including biological properties and toxicology of H₂O₂, use of chlorine dioxide, safety studies on tooth whitening, and clinical considerations of its use. Data accumulated during the last two decades demonstrate that, when used properly, peroxide-based tooth whitening is safe and effective. The most commonly seen side effects are tooth sensitivity and gingival irritation, which are usually mild to moderate and transient. So far there is no evidence of significant health risks associated with tooth whitening; however, potential adverse effects can occur with inappropriate application, abuse, or the use of inappropriate whitening products. With the knowledge on peroxide-based whitening materials and the recognition of potential adverse effects associated with the procedure, dental professionals are able to formulate an effective and safe tooth whitening regimen for individual patients to achieve maximal benefits while minimising potential risks.

Objective: The aim of this laboratory study was to investigate the effect of three commercial bleaching agents and Tooth Mousse(™) containing 10% w/w casein phosphopeptide-amorphous calcium phosphate on the hardness of tooth enamel., Methods: Sixteen human enamel specimens were exposed to one of three commercial bleaching agents with or without subsequent exposure to Tooth Mousse(™) . Nanoindentation was used to measure the hardness and reduced modulus before and after treatments., Results: When bleaching materials were applied for a short period of time following the manufacturers' instructions, there was an increase in enamel hardness and reduced modulus for some bleaching groups, with no statistically significant difference from the baseline values. After extended bleaching periods a statistically significant decrease in enamel hardness and reduced modulus was found and after applying Tooth Mousse(™) post-bleaching, the hardness and reduced modulus returned to close to baseline values., Conclusion: The application of bleaching agents for an extended period of time significantly decreases enamel hardness and the reduced modulus. The application of Tooth Mousse(™) after bleaching was able to reestablish the baseline enamel hardness and reduced modulus, decreasing the adverse effects of bleaching enamel., (© 2012 Wiley Publishing Asia Pty Ltd.)

Background: Tooth bleaching (whitening) is a conservative and cost effective treatment of discoloured teeth., Objectives: The purpose of this study was to evaluate the clinical efficacy and safety of 16% and 35% carbamide peroxide as in-office bleaching agents., Methods: Thirty adult subjects who desired to whiten their discoloured teeth were enrolled in the study. Carbamide bleaching agents, in concentrations of 16% and 35%, were used to whiten their teeth employing the spilt-arch technique/half-mouth design using vacuum formed half-arch matrix seated over the maxillary teeth for a one-hour session per week for two weeks. Outcome was monitored with Vita shade guide and photographs., Results: Twenty females and ten males, ages 18-43 years, with mean age 27.83 years, participated in the study. Tooth whitening was obtained in all subjects. Shade tab movement of 2-4 shades and 4-6 shades was recorded at first sessions then 3-5 and 5-9 shades at second sessions for 16% and 35% concentrations of carbamide peroxide respectively. The bleaching outcome was significantly better with the 35% concentration of carbamide peroxide while transient tooth sensitivity was observed in both concentrations ofthe bleaching agents., Conclusion: Carbamide peroxide in 16% and 35% concentration are effective and safe for bleaching discoloured vital teeth, however, 35% concentration gave significantly more lightening effect without additional side effects compared to 16% concentration.

Aims: To assess the safety and pharmacokinetics of a new synthetic ozonide antimalarial, OZ439, in a first-in-man, double-blind study in healthy volunteers., Methods: OZ439 was administered as single oral daily doses of a capsule formulation (50-1200 mg) or an oral dispersion (400-1600 mg, fed and fasted states) and for up to 3 days as an oral dispersion (200-800 mg day(-1)). Plasma concentrations of OZ439 and its metabolites were measured by LC-MS., Results: The pharmacokinetic (PK) profile of OZ439 was characterized by a t(max) of around 3 h, followed by a multiphasic profile with a terminal half-life of 25-30 h. The PK parameters were approximately dose proportional for each group and profiles of the metabolites followed a similar pattern to that of the parent compound. Following dosing for 3 days, accumulation was less than two-fold but steady-state was not achieved. In the presence of food, no effect was observed on the t(1/2) of OZ439 while the exposure was increased by 3 to 4.5-fold. Exposure was higher and inter-subject variability was reduced when OZ439 was administered as an oral dispersion compared with a capsule. The urinary clearance of OZ439 and its metabolites was found to be negligible and OZ439 did not induce CYP3A4. The antimalarial activity profiles of a subset of serum samples suggested that the major antimalarial activity originated from OZ439 rather than from any of the metabolites., Conclusion: The safety and pharmacokinetic profile of OZ439 merits progression to phase 2a proof of concept studies in the target population of acute uncomplicated malaria., (© 2012 Medicines for Malaria Venture (MMV). British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)

This in vitro study assessed the amount of mercury (Hg) released from a silver amalgam alloy following the application of different 10% carbamide peroxide bleaching agents. A total of 30 specimens (2 mm thick x 4 mm in diameter) were stored in deionized water at 37°C for 7 days. Next, the control group (n = 10) remained in the deionized water for 15 days, while the remaining samples were exposed to 1 of 2 bleaching agents (n = 10) for 8 hours daily (total exposure = 120 hours); for the remaining 16 hours, specimens in the test groups were stored in deionized water at 37°C under relative humidity. After this period, the quantity of Hg in the deionized water was assessed (using atomic absorption spectrophotometry) and compared to the amount of Hg at baseline. The results indicate that exposing amalgam alloys to bleaching agents released greater amounts of Hg compared to exposing samples to deionized [corrected] water.

The aim was to investigate the effects of three types (A, B and C) of stoned and dehydrated olive pomaces (OPs), differing in olive cultivar, on productive performance and meat quality of growing rabbits. The inclusion of OPs (5%) negatively affected the performance of rabbits as it reduced the feed intake, growth rate, carcass weight and dressing out percentage (P<0.05). Compared with the control, the meat of OP rabbits had a greater amount of monounsaturated and a lower amount of polyunsaturated fatty acids (P<0.05), independent of the type of OP used. Oxidative processes in the meat of OPA and OPB were higher (P<0.05), whereas OPC showed the same levels as the control group. This was due to the higher total polyphenol concentration and to the concomitant lower peroxide value of OPC. These results recommend the use of OP in rabbit diet with caution, taking into account the quality of the by-product in terms of oxidative status., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The aim of this study was to compare the effectiveness of and tooth sensitivity to 10% and 20% carbamide peroxide (CP) home-use bleaching agents and 35% and 38% hydrogen peroxide (HP) in-office bleaching agents, all of which contain desensitizing agents, in a clinical trial. Four agents were evaluated: 10% CP and 20% CP (Opalescence PF 10% and Opalescence PF 20%, Ultradent, both with 0.5% potassium nitrate and 0.11% fluoride ions), 38% HP (Opalescence Boost PF, Ultradent, with 3% potassium nitrate and 1.1% fluoride ions), and 35% HP (Pola Office, SDI, with potassium nitrate). The initial screening procedure included 100 volunteers, aged 18 to 42, with no previous sensitivity or bleaching treatment and with any tooth shade. Volunteers were randomly assigned among the technique/bleaching agent groups. A run-in period was performed 1 week before the beginning of the bleaching treatment. For the home-use bleaching technique, each volunteer was instructed to dispense gel (10% CP or 20% CP) into the trays and then insert them into his or her mouth for at least two hours per night for three weeks. For the in-office bleaching technique, the bleaching agents (38% HP or 35% HP) were prepared and used following the manufacturer's instructions, with three applications performed in each session. Three sessions were carried out with an interval of seven days between each session. The participants were evaluated before, at one week, two weeks, and three weeks after the beginning of the bleaching treatment, and again one and two weeks after the bleaching treatment ended. A shade guide (Vita Classical, Vita) was used by a blinded examiner to perform shade evaluations before bleaching and two weeks after the end of bleaching. At the time of the shade evaluations, tooth sensitivity was also recorded by asking the volunteers to classify the sensitivity during bleaching treatment as absent, mild, moderate, or severe. The present study found that 13.8% of the volunteers withdrew from the study due to tooth sensitivity, and 43.2% of the participants experienced some type of sensitivity during bleaching treatment. The χ(2) test showed that there was a significant prevalence of tooth sensitivity during bleaching treatment using the home-use 20% CP agent, with 71.4% of volunteers reporting any level of tooth sensitivity (p=0.0032). A low prevalence of tooth sensitivity was observed for volunteers who used the in-office 38% HP agent (15.0%). The Wilcoxon test (p<0.05) showed that all of the bleaching treatments were effective in bleaching teeth and that there were no differences between the final color shade results among the treatments (Kruskal-Wallis, p<0.05). This study showed that 43.2% of all the volunteers experienced mild or moderate tooth sensitivity during the treatment with bleaching agents. A higher prevalence of tooth sensitivity was observed for 71.4% of the volunteers who used the 20% CP home-use bleaching agent, which may be ascribed to the peroxide concentration and/or the time/length the agent was in contact with the dental structures.