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1.
J Dent ; 139: 104744, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37852572

RESUMO

OBJECTIVE: To evaluate the effects of activated charcoal-based products used in two presentation forms (powder or toothpaste), compared to 10 % carbamide peroxide and conventional toothpaste on aesthetic perception and psychosocial impact before and after treatment. METHODS: Fifty-six participants were divided into 4 experimental groups (n = 14). Activated charcoal-based powder (PW); Activated charcoal-based dentifrice (AC); Conventional fluoride toothpaste (CD) and 10 % carbamide peroxide (CP). All products were used for 14 days. Psychosocial impact on dental esthetics (PIDAQ), oral health impact profile (OHIP- Esthetics) and orofacial esthetics scale (OES) questionnaires were applied before and after treatment. Descriptive and exploratory data analyses were performed and analyzed using linear mixed models for repeated measures over time considering significance level of α = 0.05. RESULTS: For PIDAQ, the CP group showed significant decrease in psychological impact, aesthetic perception domains and overall score, while in the PW group, there was only a significant decrease in the psychological impact domain. Decrease in OHIP was observed for the functional limitation domain scores for treatments with CP and PW, in the psychological discomfort domain, decrease was observed for all groups, while for the OES questionnaire, significant increase in the color domain was observed for the CP group. CONCLUSION: Activated charcoal-based products showed lower scores in all questionnaires when compared with carbamide peroxide; thus, charcoal-based products promoted lower impact on quality of life and aesthetic perception. CLINICAL RELEVANCE: In this randomized clinical trial, charcoal-based OTC products had inferior quality of life and aesthetic perception results compared to conventional carbamide peroxide bleaching.


Assuntos
Clareadores , Clareadores Dentários , Clareamento Dental , Humanos , Clareamento Dental/métodos , Peróxido de Carbamida , Carvão Vegetal/uso terapêutico , Clareadores Dentários/uso terapêutico , Estética Dentária , Qualidade de Vida/psicologia , Pós , Cremes Dentais , Percepção , Peróxido de Hidrogênio/uso terapêutico , Ureia/uso terapêutico , Peróxidos/uso terapêutico
2.
Oper Dent ; 48(6): 638-647, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37881145

RESUMO

BACKGROUND: Negative effects of bleaching on dentin have previously been reported in vitro. OBJECTIVE: The purpose of this study was to determine the effect of carbamide peroxide bleaching on dentin fatigue resistance using a clinically relevant in situ model. METHODS AND MATERIALS: Following research ethics board approval, 60 human teeth requiring extraction were collected. Sterilized human dentin specimens were cut (1.2x1.2x10 mm) and secured into customized bleaching trays to be used by study participants. Participants were randomly assigned to either bleach (10% carbamide peroxide, n=23) or control (gel without bleach, n=26) treatment groups. Treatment was applied to the bleaching trays and worn overnight by participants for 14 days. After treatment completion, dentin specimens were removed from the bleaching trays and subjected to fatigue testing (10 N, 3 mm/s, 2x105 cycles) while submerged in artificial saliva. Kaplan-Meier survival analysis was conducted to compare the number of cycles to failure during fatigue testing in both groups. A log rank test was run to determine if there were differences in the survival distribution between the two groups (α<0.05). RESULTS: The median number of cycles to failure was 352 ± 202 and 760 ± 644 for the bleach and control groups, respectively. The survival distributions for the two groups were significantly different (p=0.020). Dentin fatigue resistance was significantly lower in the bleach group compared to the control. CONCLUSIONS: Direct bleaching of human dentin using an at-home tray bleaching protocol in situ reduced dentin fatigue resistance. This has implications for tooth fracture risk and longevity.


Assuntos
Peróxidos , Clareamento Dental , Humanos , Peróxido de Carbamida/farmacologia , Peróxidos/uso terapêutico , Ureia , Dentina , Clareamento Dental/efeitos adversos , Clareamento Dental/métodos , Peróxido de Hidrogênio/farmacologia
3.
BMC Oral Health ; 23(1): 758, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833672

RESUMO

BACKGROUND: Nowadays bleaching procedures have gained popularity in orthodontic patients. Peroxide and Carbamide acids are the common agents which are used in in-office and at home bleaching techniques. Consequently, the Bonding adhesion to the enamel can be influenced by the orthodontic phase and the residual peroxide might interfere with the polymerization and the adhesion of the brackets. Frequent debonding of the brackets from teeth after the bleaching procedure could cause the lengthening of the therapy and promote irregularities on enamel surface derived from an additional bonding phase of the brackets. The aim of this systematic review is to appraise the influence regarding the effect of the bleaching procedure on the bond strength of orthodontic brackets. METHODS: An electronic database search was performed. Search terms included: bleaching, brackets, adhesion; data were extracted and summarized. Risk of bias was assessed using the Chocrane risk of bias tool, adapted for in vitro studies. RESULTS: A total of 8689 articles were screened and 11 studies met the inclusion criteria of this systematic review. 1000 teeth of human and bovine origin were analyzed for the shear bond strength (SBS) of stainless and ceramic brackets after the bleaching treatments. All the authors divided the groups in different subgroups with different bleaching agents and in different concentration. The SBS value allowed to demonstrate the necessity to delay the bonding of the brackets for two weeks after a bleaching treatment and its improvement when tooth mousse or antioxidants agents are used. CONCLUSIONS: The SBS values and the delay of the bonding procedure must be considered in dental practice and clinical strategies are necessary in order to avoid drawbacks which could cause the debonding of the brackets after bleaching due to the alterations of the dental substrate, thus interfering with the orthodontic treatments.


Assuntos
Colagem Dentária , Braquetes Ortodônticos , Clareamento Dental , Humanos , Animais , Bovinos , Clareamento Dental/efeitos adversos , Braquetes Ortodônticos/efeitos adversos , Colagem Dentária/métodos , Peróxidos/uso terapêutico , Peróxidos/química , Ureia/uso terapêutico , Ureia/química , Resistência ao Cisalhamento , Análise do Estresse Dentário , Teste de Materiais
4.
Radiat Res ; 200(5): 456-461, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37758035

RESUMO

Diffuse intrinsic pontine gliomas (DIPG) are an aggressive type of pediatric brain tumor with a very high mortality rate. Surgery has a limited role given the tumor's location. Palliative radiation therapy alleviates symptoms and prolongs survival, but median survival remains less than 1 year. There is no clear role for chemotherapy in DIPGs as trials adding chemotherapy to palliative radiation therapy have failed to improve survival compared to radiation alone. Thus, there is a critical need to identify tissue-specific radiosensitizers to improve clinical outcomes for patients with DIPGs. Pharmacologic (high dose) ascorbate (P-AscH-) is a promising anticancer therapy that sensitizes human tumors, including adult high-grade gliomas, to radiation by acting selectively as a generator of hydrogen peroxide (H2O2) in cancer cells. In this study we demonstrate that in contrast to adult glioma models, P-AscH- does not radiosensitize DIPG. DIPG cells were sensitive to bolus of H2O2 but have faster H2O2 removal rates than GBM models which are radiosensitized by P-AscH-. These data support the hypothesis that P-AscH- does not enhance DIPG radiosensitivity, likely due to a robust capacity to detoxify and remove hydroperoxides.


Assuntos
Antineoplásicos , Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Glioma , Criança , Adulto , Humanos , Glioma Pontino Intrínseco Difuso/tratamento farmacológico , Glioma Pontino Intrínseco Difuso/patologia , Neoplasias do Tronco Encefálico/radioterapia , Neoplasias do Tronco Encefálico/patologia , Peróxidos/uso terapêutico , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/uso terapêutico , Glioma/radioterapia , Glioma/patologia , Antineoplásicos/uso terapêutico
5.
Artigo em Inglês | MEDLINE | ID: mdl-37347995

RESUMO

This study aimed to clinically evaluate the effectiveness of two different at-home whitening protocols and to determine which is more effective: applying the whitening gel (16% carbamide peroxide) every 24 hours (Group A) or every 48 hours (Group B) for 2 weeks. Group C received a placebo gel (glycerin) without peroxide, which was applied every 24 hours for 2 weeks. The differences in terms of tooth sensitivity were also analyzed. A sample of 60 patients was divided into three groups of 20 patients. To compare the groups, color measurements were made using a spectrophotometer, and Student t test was used for independent samples. The confidence level was set at 95% (P ≤ .05). No statistically significant differences were found between Groups A and B (P > .05). The study concluded that 16% carbamide peroxide was equally effective when applied with either protocol and obtained the same results, but the 48-hour application protocol produced less sensitivity than the 24-hour application protocol.


Assuntos
Clareadores Dentários , Clareamento Dental , Humanos , Peróxido de Carbamida , Cor , Sensibilidade da Dentina/tratamento farmacológico , Peróxidos/uso terapêutico , Clareamento Dental/métodos , Clareadores Dentários/uso terapêutico
6.
Pediatr Dermatol ; 40(3): 452-459, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36949579

RESUMO

BACKGROUND/OBJECTIVES: Topical clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel (IDP-126) is the first fixed-dose triple-combination formulation in development for acne. This post hoc analysis investigated efficacy and safety of IDP-126 in children and adolescents with moderate-to-severe acne. METHODS: In a randomized, double-blind phase 2 study (NCT03170388), participants ≥9 years of age with moderate-to-severe acne were eligible for randomization (1:1:1:1:1) to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. This post hoc analysis of pediatric participants (n = 394) included children and adolescents up to 17 years of age. Assessments included treatment success, inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At Week 12, treatment success rates were significantly greater with IDP-126 (55.8%) than with vehicle (5.7%; p < .001) or any of the dyad combinations (range: 30.8%-33.9%; p < .01, all). Lesion reductions with IDP-126 were also significantly greater than with vehicle (inflammatory: 78.3% vs. 45.1%; noninflammatory: 70.0% vs. 37.6%; p < .001, both) and 9.2%-16.6% greater than with any of the dyad combinations. Increases (improvements) from baseline in Acne-QoL domain scores were generally greater with IDP-126 than in any other treatment group. The most common treatment-related TEAEs across treatment groups were application site pain and dryness. Most treatment-related TEAEs were of mild-to-moderate severity. CONCLUSION: IDP-126 gel-a novel fixed-dose, triple-combination topical formulation for acne-demonstrated superior efficacy to vehicle and three dyad component gels and was well tolerated in children and adolescents with moderate-to-severe acne.


Assuntos
Acne Vulgar , Fármacos Dermatológicos , Humanos , Criança , Adolescente , Recém-Nascido , Adapaleno/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Peróxido de Benzoíla/efeitos adversos , Qualidade de Vida , Peróxidos/uso terapêutico , Combinação de Medicamentos , Índice de Gravidade de Doença , Acne Vulgar/tratamento farmacológico , Clindamicina/efeitos adversos , Resultado do Tratamento , Géis/uso terapêutico , Método Duplo-Cego
7.
J Esthet Restor Dent ; 35(2): 423-430, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36398920

RESUMO

OBJECTIVE: Assess the effects of activated charcoal-based products on whitening and changes on dental enamel surface. MATERIAL AND METHODS: Fifty-two blocks of bovine dental enamel were randomly distributed in four groups (n = 13): brushing with activated charcoal-based powder (PW); brushing with activated charcoal-based dentifrice (AC); brushing with a conventional dentifrice containing 1450 ppm of fluoride (CD); and whitening with 10% carbamide peroxide (CP). Color, microhardness, and surface alteration were analyzed at baseline and after 14 days of treatment. Three samples per group were randomly selected and examined using scanning electron microscopy (SEM) to analyze the morphology. RESULTS: PW exhibited greater color change for the ΔE00 , ΔWID, Δb* and ΔL* parameters than other groups (p < 0.05). After treatment, microhardness decreased in AC and CP groups (p < 0.05). Also, PW and AC groups showed more surface alteration than CD and CP (p < 0.001). Changes in the morphology of dental enamel were observed by SEM in PW and AC groups. CONCLUSION: Activated charcoal-based products showed a lower whitening effect than 10% carbamide peroxide. These products also influenced dental enamel microhardness, resulting in greater surface alteration. CLINICAL SIGNIFICANCE: Activated charcoal-based products promoted minimum whitening effects with significant enamel surface alteration. The 10% carbamide peroxide was more effective for whitening and caused slight enamel surface alteration.


Assuntos
Dentifrícios , Clareamento Dental , Animais , Bovinos , Peróxido de Carbamida , Carvão Vegetal/farmacologia , Esmalte Dentário , Dentifrícios/farmacologia , Dentifrícios/uso terapêutico , Peróxidos/farmacologia , Peróxidos/uso terapêutico , Clareamento Dental/métodos , Ureia/farmacologia , Ureia/uso terapêutico
8.
Int J Esthet Dent ; 17(4): 448-467, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36426616

RESUMO

OBJECTIVE: The objective of the present study was to assess the progress and efficiency of at-home bleaching protocols with 10% carbamide peroxide using a new methodology based on dental photography. MATERIALS AND METHODS: A 4-week overnight at-home bleaching protocol using whitening trays and 10% carbamide peroxide was performed on 52 patients. The tooth color was analyzed using standardized photographs taken every week for 4 weeks and at 4 months posttreatment. The values of the color evolution (ΔE00), L*, a*, and b* were also measured and used to assess the evolution of the chroma, luminosity, and hue using the CIEDE2000 formula. The statistical analyses were conducted at a significance level of P < 0.05 by means of a repeated measures analysis of variance (ANOVA). RESULTS: The tooth color changed the most, and thus the highest ΔE00 was observed, after the first week of treatment. The color continued to change but to a lesser degree during the following weeks. After 4 weeks, the treatment proved to be very effective. Four months after the end of treatment, a color relapse was observed, though it was hardly perceptible to the human eye. The luminosity (L') changed significantly between the beginning and the end of treatment, affecting the maxilla to a greater extent. The chroma evolution showed a high variance and a low relapse for both jaws. The hue was not affected significantly during the treatment and the stabilization. CONCLUSIONS: Within the limitations of the present study, the authors were able to assess the progress and efficiency of at-home bleaching with 10% carbamide peroxide in terms of chroma, luminosity, and hue using a new methodology based on dental photography. CLINICAL SIGNIFICANCE: This new method is effective and enables a reliable analysis of the evolution of a dental bleaching treatment, turning dental photo-graphy into an even more powerful tool for analysis and communication. It can also be used as a proof-of-concept, paving the way for further research on objective monitoring and evaluation of dental treatments using dental photography.


Assuntos
Clareadores Dentários , Clareamento Dental , Humanos , Peróxido de Carbamida , Clareamento Dental/métodos , Peróxidos/uso terapêutico , Ureia/uso terapêutico , Cor
9.
Langmuir ; 38(40): 12307-12315, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36154182

RESUMO

Chemodynamic therapy (CDT) is a promising hydroxyl radical (•OH)-mediated tumor therapeutic method with desirable tumor specificity and minimal side effects. However, the efficiency of CDT is restricted by the pH condition, insufficient H2O2 level, and overexpressed reductive glutathione (GSH), making it challenging to solve these problems simultaneously to improve the efficacy of CDT. Herein, a kind of polyvinylpyrrolidone-stabilized, sorafenib-loaded copper peroxide (CuO2-PVP-SRF) nanoparticle (NPs) was designed and developed for enhanced CDT against tumor cells through the synergetic pH-independent Fenton-like, H2O2 self-supplying, and GSH depletion strategy. The prepared CuO2-PVP-SRF NPs can be uptaken by 4T1 cells to specifically release Cu2+, H2O2, and SRF under acidic conditions. The intracellular GSH can be depleted by SRF-induced system xc- dysfunction and Cu2+-participated redox reaction, causing the inactivation of GPX4 and generating Cu+. A great amount of •OH was produced in this reducing capacity-disrupted condition by the Cu+-mediated Fenton-like reaction, causing cell apoptosis and lipid hydroperoxide accumulation-induced ferroptosis. They display an excellent 4T1 cell killing outcome through the improved •OH production capacity. The CuO2-PVP-SRF NPs display elevated therapeutic efficiency of CDT and show good promise in further tumor treatment applications.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Cobre/farmacologia , Glutationa , Humanos , Peróxido de Hidrogênio , Radical Hidroxila , Peróxidos Lipídicos/farmacologia , Neoplasias/tratamento farmacológico , Oxirredução , Peróxidos/farmacologia , Peróxidos/uso terapêutico , Povidona , Sorafenibe/farmacologia , Microambiente Tumoral
10.
Med Sci Monit ; 28: e937051, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36110037

RESUMO

Myocardial injury and necrosis caused by hyperlipidemia have been investigated by several researchers. Their pathogenesis and molecular basis are different from those of the more common clinical ischemic myocardial injury. Hyperlipidemia leads to peroxide accumulation in the cardiomyocytes, causes lipid overload, decreases the antioxidant capacity of the body, and promotes the inflammatory response. Furthermore, hyperlipidemia causes changes in the structure and function of mitochondria in the cardiomyocytes, which results in their injury and necrosis. Many previous studies have shown that metabolic diseases (eg, obesity and diabetes) and chemical poisoning can lead to hyperlipidemic myocardial injury and necrosis. Moreover, it has been observed that this pathological process can be inhibited by many small molecular substances. In the clinic, myocardial damage can be prevented or reduced by lowering the levels of triglyceride and cholesterol. Myocardial damage can also be regulated via the molecular pathway of myocardial injury caused by hyperlipidemia so that the disease can be treated. The present article reviewed the recent findings reported on the mechanisms of myocardial damage due to hyperlipidemia.


Assuntos
Hiperlipidemias , Antioxidantes/uso terapêutico , Humanos , Hiperlipidemias/tratamento farmacológico , Lipídeos , Necrose , Peróxidos/uso terapêutico , Triglicerídeos
11.
Am J Dent ; 35(4): 191-196, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35986934

RESUMO

PURPOSE: To evaluate the influence of diet and exposure to red wine on the treatment velocity, clinical results, postoperative tooth sensitivity, and patient satisfaction after tooth bleaching. METHODS: 45 subjects undergoing home bleaching with 16% carbamide peroxide (CP) were randomly separated into three groups, depending on the restriction of colored food and the use of a red wine mouthwash. Shades of teeth 11 and 21 were assessed using a digital spectrophotometer (VITA Easy Shade) at T0 (before treatment), T7 (7 days after treatment), T15 (15 days after treatment), and T30 (30 days after treatment). The assessments were verified using the CIELab system (values of L*, a*, and b*) and the change in shade was calculated (ΔE, ΔL, Δa, and Δb). RESULTS: No statistically significant differences in ΔE, ΔL, Δa, and Δb were found between the groups. However, at T7, the group restricted from colored foods without red wine mouthwash had meaningful variations in L*, a*, and b*. Statistically, there was no difference in tooth sensitivity between the groups in the 7- and 15-day periods. Patients in the restricted colored foods without red wine mouthwash group were more satisfied after the end of treatment. CLINICAL SIGNIFICANCE: Tooth bleaching with 16% carbamide peroxide may be performed in subjects with colorant-rich diets without influencing the clinical outcome.


Assuntos
Sensibilidade da Dentina , Clareadores Dentários , Clareamento Dental , Vinho , Peróxido de Carbamida , Cor , Sensibilidade da Dentina/tratamento farmacológico , Sensibilidade da Dentina/prevenção & controle , Dieta , Humanos , Peróxido de Hidrogênio , Antissépticos Bucais , Peróxidos/uso terapêutico , Clareamento Dental/métodos , Clareadores Dentários/uso terapêutico , Ureia/uso terapêutico
12.
Oper Dent ; 47(3): E119-E130, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35649221

RESUMO

OBJECTIVE: This study investigated the influence of the viscosity and kind of thickener of 35% hydrogen peroxide bleaching gels on the tooth (color change, demineralization of enamel, and permeation) and on the gel [reactive oxygen species (ROS), pH, and peroxide concentration]. METHODS AND MATERIALS: Two hundred forty specimens were divided into groups of bleaching gels with different thickeners (CAR, carbomer; ASE, alkali swellable emulsion; MSA, modified sulfonic acid polymer; SSP, semisynthetic polysaccharide; PAC, particulate colloids) in three viscosities (low: 50,000 cP; medium: 250,000 cP; high: 1,000,000 cP). Color change (ΔEab), demineralization of enamel by Knoop microhardness (KHN) reduction analysis, and peroxide permeation (PP) were analyzed in the specimens, while pH, peroxide concentration (PC), and ROS were evaluated in the gels. Data were analyzed by two-way ANOVA (α=0.05). RESULTS: The higher viscosity gels reduced ΔEab, PP, enamel softening, and ROS in relation to the lower viscosity gels. However, the drop in pH and PC were higher in the more viscous gels. Gels with MSA produced higher ΔEab compared with SSP and ASE. The PP was higher for PAC, and smaller for SSP and CAR. The KHN reduction was higher for CAR and smaller for PAC. The higher pH reduction was seen for ASE and CAR, and the smaller for SSP. The PC reduction was higher for SSP and smaller for CAR. More ROS were observed for MSA and fewer for ASE. CONCLUSIONS: Increased gel viscosity was associated with reduced color change, permeation, demineralization of enamel, and ROS, and led to increased peroxide decomposition and pH alteration during the treatment. The kind of thickener significantly interfered with the treatment effects.


Assuntos
Clareadores Dentários , Clareamento Dental , Desmineralização do Dente , Géis , Dureza , Humanos , Peróxido de Hidrogênio/química , Peróxidos/uso terapêutico , Espécies Reativas de Oxigênio , Clareamento Dental/métodos , Clareadores Dentários/farmacologia , Clareadores Dentários/uso terapêutico , Viscosidade
13.
Am J Dent ; 35(1): 20-24, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35316588

RESUMO

PURPOSE: To evaluate the effectiveness of five whitening toothpastes applied three times a day for 4 weeks. METHODS: 25 human extracted teeth were selected. Two peroxide-based dental bleaching pastes (professionally delivered): Enawhite 2.0 (En), Whitekin (Wk); and three over the counter whitening toothpastes: Opalescence whitening toothpaste (Op), Colgate max White expert White (Cg) Premium activated charcoal (Cr) were used. Teeth were brushed for 4 weeks, three times a day. Color was measured with a spectrophotometer according to the CIELab system. ΔEab, W* and ΔE00 values were calculated at baseline, at the end of the treatment, and 1 week after the end of treatment. Data analysis was performed using a generalized estimating equations model, evaluating the effect of treatment, time and interaction (P< 0.05). RESULTS: ΔEab values ranged from 5.01 for En to 3.22 for Wk after the 4-week treatment period. One week after the end of treatment, ΔEab ranged from 5.91 for Cr to 3.62 for Op (P> 0.05 between groups). The closest to pure white (W* differences between baseline and after 1 week from the end of treatment) was for En and Wk. ΔE00 values after 4 weeks of treatment ranged from 3.23 for En to 1.79 for Wk. One week after the end of treatment, the ΔE00 ranges were between 3.31 for Cr to 2.03 for Op (P> 0.05 between groups). CLINICAL SIGNIFICANCE: All the evaluated whitening toothpastes improved dental color values higher than those perceptible and acceptable at the 50:50 threshold.


Assuntos
Clareamento Dental , Descoloração de Dente , Dente , Humanos , Peróxidos/uso terapêutico , Descoloração de Dente/tratamento farmacológico , Cremes Dentais/uso terapêutico
14.
ACS Appl Mater Interfaces ; 13(37): 44096-44107, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34499466

RESUMO

Mitochondria are the "power plant" of the cell, providing a constant source of energy, and are involved in a variety of intracellular signaling pathways. Among these pathways, Ca2+ homeostasis is closely related to the normal function of mitochondria. By destroying the Ca2+ steady state of mitochondria and disrupting their multiple cellular activities, tumor cell killing can be achieved. In addition, the presence of an intracellular oxidative stress state triggers the closure of cellular calcium channels, which leads to intracellular Ca2+ retention and enrichment. We designed a targeted and tumor microenvironment (TME)-responsive CaO2-based nanosystem that can selectively target cancer cells for pH-controlled degradation and drug release, alter cellular physiological mechanisms by disrupting Ca2+ homeostasis in an artificial manner, and introduce mitochondrial Ca2+ excess-mediated apoptosis. Meanwhile, the production of Ca(OH)2 will raise the pH of the microenvironment and subsequently promote the oxidation process of glutathione by H2O2 released from CaO2 degradation, achieving the goal of remodeling TME. Moreover, calcium overload of tumor cells and calcification of tissues can both inhibit tumor growth and act as a contrast agent for computed tomography imaging.


Assuntos
Antineoplásicos/uso terapêutico , Cálcio/metabolismo , Mitocôndrias/efeitos dos fármacos , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Peróxidos/uso terapêutico , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Ácido Hialurônico/química , Estruturas Metalorgânicas/química , Camundongos , Nanopartículas/química , Peróxidos/química , Povidona/química , Microambiente Tumoral/efeitos dos fármacos
15.
ACS Appl Mater Interfaces ; 13(38): 45335-45345, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34543000

RESUMO

Immunotherapy is currently an important adjuvant therapy for malignant tumors besides surgical treatment. However, the heterogeneity and low immunogenicity of the tumor are two main challenges of the immunotherapy. Here, we have constructed a nanoplatform (CP@mRBC-PpIX) to realize reversion of the tumor acidosis and hypoxia through alkali and oxygen generation triggered by tumor acidosis. By targeting tumor universal features other than endogenous biomarkers, it was found that CP@mRBC-PpIX could polarize tumor-associated macrophages to anti-tumor M1 phenotype macrophages to enhance tumor immune response. Furthermore, under regional light irradiation, the reactive oxygen species produced by photosensitizers located in CP@mRBC-PpIX could increase the immunogenicity of tumors, so that tumor changes from an immunosuppressive "cold tumor" to an immunogenic "hot tumor," thereby increasing the infiltration and response of T cells, further amplifying the effect of immunotherapy. This strategy circumvented the problem of tumor heterogeneity to realize a kind of broad-spectrum immunotherapy, which could effectively prevent tumor metastasis and recurrence.


Assuntos
Antineoplásicos/uso terapêutico , Membrana Eritrocítica/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Protoporfirinas/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Cobre/química , Cobre/uso terapêutico , Humanos , Imunidade/efeitos dos fármacos , Imunoterapia , Luz , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Neoplasias/metabolismo , Peróxidos/química , Peróxidos/uso terapêutico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/uso terapêutico , Protoporfirinas/química , Protoporfirinas/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T/efeitos dos fármacos
17.
Am J Trop Med Hyg ; 103(5): 1910-1917, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32815508

RESUMO

Liver transaminase elevations after treatment in malaria volunteer infection studies (VISs) have raised safety concerns. We investigated transaminase elevations from two human Plasmodium vivax VISs where subjects were treated with chloroquine (n = 24) or artefenomel (n = 8) and compared them with studies in Thailand (n = 41) and Malaysia (n = 76). In the VISs, alanine transaminase (ALT) increased to ≥ 2.5 × upper limit of normal (ULN) in 11/32 (34%) volunteers, peaking 5-8 days post-treatment. Transaminase elevations were asymptomatic, were not associated with elevated bilirubin, and resolved by day 42. The risk of an ALT ≥ 2.5 × ULN increased more than 4-fold (odds ratio [OR] 4.28; 95% CI: 1.26-14.59; P = 0.02) for every log10 increase in the parasite clearance burden (PCB), defined as the log-fold reduction in parasitemia 24 hours post-treatment. Although an elevated ALT ≥ 2.5 × ULN was more common after artefenomel than after chloroquine (5/8 [63%] versus 6/24 [25%]; OR 5.0; 95% CI: 0.91-27.47; P = 0.06), this risk disappeared when corrected for PCB. Peak ALT also correlated with peak C-reactive protein (R = 0.44; P = 0.012). Elevations in ALT (≥ 2.5 × ULN) were less common in malaria-endemic settings, occurring in 1/41 (2.5%) Thai patients treated with artefenomel, and in none of 76 Malaysians treated with chloroquine or artemisinin combination therapy. Post-treatment transaminase elevations are common in experimental P. vivax infection but do not appear to impact on participant safety. Although the mechanism of these changes remains uncertain, host inflammatory response to parasite clearance may be contributory.


Assuntos
Adamantano/análogos & derivados , Alanina Transaminase/sangue , Antimaláricos/uso terapêutico , Hepatopatias/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Peróxidos/uso terapêutico , Plasmodium vivax/isolamento & purificação , Adamantano/uso terapêutico , Adulto , Artemisininas/uso terapêutico , Cloroquina/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Hepatopatias/sangue , Hepatopatias/parasitologia , Testes de Função Hepática , Malária Vivax/sangue , Malária Vivax/parasitologia , Malásia , Masculino , Parasitemia/tratamento farmacológico , Tailândia , Adulto Jovem
18.
Mol Pharm ; 17(7): 2749-2759, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32574056

RESUMO

Recent studies have shown that the solubilization of two antimalarial drug candidates, artefenomel (OZ439) and ferroquine (FQ), designed to provide a single-dose combination therapy for uncomplicated malaria can be enhanced using milk as a lipid-based formulation. However, milk as an excipient faces significant quality and regulatory hurdles. We therefore have investigated infant formula as a potential alternative formulation approach. The significance of the lipid species present in a formula with different lipid compositions upon the solubilization of OZ439 and FQ during digestion has been investigated. Synchrotron small-angle X-ray scattering was used to measure the diffraction from a dispersed drug during digestion and thereby determine the extent of drug solubilization. High-performance liquid chromatography was used to quantify the amount of drug partitioned into the digested lipid phases. Our results show that both the lipid species and the amount of lipids administered were key determinants for the solubilization of OZ439, while the solubilization of FQ was independent of the lipid composition. Infant formulas could therefore be designed and used as milk substitutes to tailor the desired level of drug solubilization while circumventing the variability of components in naturally derived milk. The enhanced solubilization of OZ439 was achieved during the digestion of medium-chain triacylglycerols (MCT), indicating the potential applicability of MCT-fortified infant formula powder as a lipid-based formulation for the oral delivery of OZ439 and FQ.


Assuntos
Adamantano/análogos & derivados , Aminoquinolinas/uso terapêutico , Antimaláricos/uso terapêutico , Compostos Ferrosos/uso terapêutico , Fórmulas Infantis/química , Lipídeos/química , Malária/tratamento farmacológico , Metalocenos/uso terapêutico , Peróxidos/uso terapêutico , Adamantano/uso terapêutico , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Digestão , Excipientes/química , Ácidos Graxos/química , Humanos , Lactente , Espectrometria de Massas , Leite/química , Espalhamento a Baixo Ângulo , Solubilidade , Triglicerídeos/química
19.
Eur Arch Paediatr Dent ; 21(5): 565-571, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31784871

RESUMO

AIM: Understand EAPD members' practices of vital bleaching for children with dental anomalies. METHODS: An anonymous online survey sent via EAPD in January 2019, consisting of 13 questions with possible multiple answers and free text. RESULTS: 110 responses from 24 countries were obtained. The majority worked in hospitals/universities (n = 69, 63%) or private practices (n = 50, 46%) and were specialists (n = 62, 57%) or senior academics (n = 35, 32%). Most respondents (n = 74 68%) did not provide vital bleaching for children. 88 respondents (80%) belonged to EU: of these, 46 (52%) were not aware of bleaching regulations. For respondents who provided bleaching 26 (72%) undertook home bleaching, using 10% carbamide peroxide (n = 21, 58%), most commonly for 2 weeks (n = 14, 39%), following establishment of the permanent dentition (n = 21, 58%). Deciding factors included: extent (n = 27, 75%) and shade (n = 26, 72%) of discolouration and child being teased by peers (n = 23, 64%). Main reasons for not bleaching included: concerns with side effects (n = 41; 55%) and not agreeing with bleaching (n = 23, 31%). Dentists who did not bleach managed a range of conditions, most frequently molar-incisor hypomineralisation (n = 57; 77%). The majority provided composite restorations with removal of tooth structure (n = 50; 68%) with a number opting for no treatment (n = 27, 37%). CONCLUSION: This study shows wide variations in treatment of children's dental anomalies across Europe. Fears of adverse effects and personal beliefs seemed to be the main deterrents to bleaching in children. Clinicians who provided bleaching tended to opt for more conservative techniques and to take children's concerns into consideration.


Assuntos
Clareamento Dental , Criança , Combinação de Medicamentos , Europa (Continente) , Humanos , Peróxidos/uso terapêutico , Inquéritos e Questionários , Ureia
20.
Orthopedics ; 41(6): e756-e764, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30321442

RESUMO

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.].


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Procedimentos Ortopédicos , Peróxidos/uso terapêutico , Infecção da Ferida Cirúrgica/prevenção & controle , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/efeitos adversos , Humanos , Peróxidos/administração & dosagem , Peróxidos/efeitos adversos
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