Nonclinical evaluation of a Vitis vinifera extract towards a novel antiaging cosmetic ingredient.

BACKGROUND: Skin aging is regulated by multiple physiological processes, such as oxidative stress. Natural products have been considered as a promising source of antioxidant compounds. As a result, few innovative products on the market based on natural products tackle additional underlying mechanisms of skin aging. AIMS: The present work reports the nonclinical evaluation of a novel extract from the skin of V. vinifera fruits (codified as ACH37 extract), with the aim of supporting its use as an antiaging cosmetic ingredient candidate in clinical trials. METHODS: We employed enzymatic, phenotypic, and gene expression assays, both in vitro and ex vivo, to investigate the action of the ACH37 extract in different biological processes that could be related to skin aging mechanisms. RESULTS: The ACH37 extract was able to scavenge reactive oxygen species (DPPH, O2 - ), prevent inflammation (LPS- and UV-induced COX-2, IL-1ß, and IL-8 expression), modulate extracellular matrix remodeling (inhibiting elastase, MMP-1, MMP-3, and MMP-12, as well as associated expression), increase telomere length, telomerase activity, and reverse the UV-induced suppression of genes involved in skin protection. In addition, the ACH37 extract permeated human skin explants and presented antioxidant efficacy ex vivo. CONCLUSION: The results indicated that the ACH37 extract acts on multiple targets commonly related to skin aging, being a promising antiaging active ingredient candidate to be further investigated in clinical trials.

Análise do perfil de liberação do princípio ativo peróxido de hidrogênio por diferentes géis clareadores dentais / Analysis of the release profile of the active ingredient hydrogen peroxide by different tooth whitening gels

O objetivo desse estudo foi analisar o perfil de liberação do princípio ativo peróxido de hidrogênio por diferentes géis clareadores no decorrer do período de aplicação. Para tal diferentes géis clareadores à base de peróxido de hidrogênio para uso na técnica em consultório foram levados à câmara doadora de uma célula de difusão vertical (célula Franz). Foi empregado como meio de difusão uma membrana de éster de celulose com porosidade de 100-500 Daltons. A câmara receptora foi preenchida com água ultrapura. Os seguintes géis foram testados: Whiteness HP (FGM), Whiteness HP Blue (FGM), Whiteness HP Automix (FGM), Potenza Bianco (PHS do Brasil), Opalescence Boost (Ultradent), e Pola Office Plus (SDI); solução de peróxido 35% controle. O peróxido de hidrogênio liberado pelo gel se difundiu através da membrana e se misturou com a água na câmara receptora. Uma amostra de 40µl foi coletada da câmara receptora a cada 5 min, durante 45 minutos e foi reposto o mesmo volume de 40 µl em água ultrapura. A concentração de peróxido na amostra (mg/ml) foi determinada em triplicata a cada momento, utilizando um espectrofotômetro leitor de microplacas e reagente enzimático. A normalidade e homoscedasticidade dos dados foram avaliadas pelos testes de Shapiro-Wilk e Levene. Os dados de quantidade acumulada de peróxido foram submetidos ao teste de análise de variância ANOVA a 2 fatores (tipo de gel x tempo) e teste de Tukey. Para todas as análises foi adotado um nível de significância de 5%. Diferenças significativas foram observadas para os fatores agente clareador (p=0,0001) e tempo (p=0,0001), assim como para a interação entre eles (p=0,0001). Os resultados do teste de Tukey para o fator agente clareador quanto à quantidade cumulativa de peróxido foram: WHPB-14,04(6,60)a, WHP19,51(8,61)b, WHPA-23,20(10,48)c, POP-26,53(11,13)d, PB-28,29(10,99)de, OPB31,03(11,81)e, Controle 79,12(32,27)f. Para o fator tempo, em minutos, os resultados foram: 5 9,64(6,70)a, 10-17,42(11,60)b, 15-24,03(16,86)c, 20-29,50(20,44)d, 25-33,93(23,00)e, 30-38,41(25,83)f, 35-41,52(27,32)fg, 40-44,11(28,47)gh, 45- 46,50(29,72)h. Os resultados do teste ANOVA de medidas repetidas mostraram diferenças significativas (p=0,00) em relação a concentração inicial e final de peróxido para os fatores agente clareador, momento de leitura e para a interação entre eles. Agentes clareadores com maior concentração inicial de peróxido de hidrogênio apresentaram maior liberação cumulativa do ingrediente ativo; a liberação de peróxido de hidrogênio de diferentes géis clareadores ocorre de maneira gradual em relação ao tempo de aplicação, porém essa liberação não ocorre de maneira constante.(AU)

The aim of this study was to analyze the release profile of the active ingredient hydrogen peroxide by different bleaching gels over the course of the application period. For this purpose, different bleaching gels based on hydrogen peroxide for use in the in-office technique were taken to the donor chamber of a vertical diffusion cell (Franz cell). A cellulose ester membrane with a porosity of 100-500 Daltons was used as diffusion medium. The receiving chamber was filled with ultrapure water. The following gels were tested: Whiteness HP (FGM), Whiteness HP Blue (FGM), Whiteness HP Automix (FGM), Potenza Bianco (PHS do Brasil), Opalescence Boost (Ultradent), and Pola Office Plus (SDI); 35% peroxide control solution. The hydrogen peroxide released by the gel diffused through the membrane and mixed with the water in the receiving chamber. A 40µl sample was collected from the receiving chamber every 5 min for 45 minutes and the same volume of 40 µl was replaced in ultrapure water. The peroxide concentration in the sample (mg/ml) was determined in triplicate at each time point, using a microplate reader spectrophotometer and enzymatic reagent. Data normality and homoscedasticity were evaluated using the Shapiro-Wilk and Levene tests. Accumulated amount of peroxide data was submitted to 2-way ANOVA test of variance (type of gel x time) and Tukey's test. For all analyses, a significance level of 5% was adopted. Significant differences were observed for the factors bleaching agent (p=0.0001) and time (p=0.0001), as well as for the interaction between them (p=0.0001). The results of the Tukey test for the bleaching agent factor regarding the cumulative amount of peroxide were: WHPB-14.04(6.60)a, WHP-19.51(8.61)b, WHPA-23.20(10 ,48)c, POP-26.53(11.13)d, PB 28.29(10.99)de, OPB-31.03(11.81)e, Control-79.12(32.27) )f. For the time factor, in minutes, the results were: 5-9.64(6.70)a, 10-17.42(11.60)b, 15-24.03(16.86)c, 20- 29.50(20.44)d, 25-33.93(23.00)e, 30- 38.41(25.83)f, 35-41.52(27.32)fg, 40-44, 11(28.47)gh, 45-46.50(29.72)h. The results of the repeated measures ANOVA test showed significant differences (p=0.00) in relation to the initial and final peroxide concentration for the factors bleaching agent, reading time and the interaction between them. Bleaching agents with a higher initial concentration of hydrogen peroxide showed a greater cumulative release of the active ingredient; The release of hydrogen peroxide from different whitening gels occurs gradually in relation to the application time, but this release does not occur constantly. (AU)

Avaliação dos repelentes: efeitos na saúde humana / Evaluation of repellents: effects on human health / Evaluación de repelentes: efectos sobre la salud humana

Este artigo teve como objetivo avaliar os efeitos do uso de repelentes na população brasileira. Para alcançar o objetivo proposto, foram utilizadas as metodologias da revisão de literatura e a pesquisa documental junto à ANVISA referentes aos repelentes registrados e comercializados no Brasil. De acordo com a RDC nº 7 de 2015 da ANVISA, os repelentes são classificados como produtos de Grau 2, compostos por Produtos de Higiene Pessoal, Cosméticos e Perfumes. Nessa categoria, constatou-se a existência de 113 produtos registrados para comercialização no Brasil. Verificou-se que, apesar do aumento do consumo devido às doenças causadas por picada dos mosquitos Aedes aegypti, a maioria dos repelentes comercializados possuem como princípio ativo as substâncias DEET, Icaridina ou IR3535, não resultando em reações tóxicas relevantes para a população, visto que, essas substâncias são de baixa toxicidade ou atóxicas, como é o caso do IR3535. Faz-se necessário considerar que o uso desses produtos deve seguir rigorosamente as orientações dos fabricantes disponíveis nos rótulos das embalagens no que tange à aplicação, reaplicação, frequência e uso específico para crianças, gestantes e lactantes. No que se refere à eficácia, a Icaridina apresenta-se como mais eficaz que o IR3535 quando considerados os fatores tempo de proteção versus concentração do princípio ativo. Entretanto, a Icaridina, em alguns casos, pode apresentar moderada toxicidade, enquanto que, o IR3535 é atóxico. Observa-se ainda, que mesmo diante desse cenário, o DEET é o mais comercializado e amplamente estudado no país.

This article aimed to evaluate the effects of the use of repellents in the Brazilian population. To achieve the proposed objective, the methodologies of literature review and documentary research with ANVISA regarding repellents registered and marketed in Brazil were used. According to ANVISA's RDC No. 7 of 2015, repellents are classified as Grade 2 products, composed of Personal Hygiene Products, Cosmetics and Perfumes. In this category, it was found the existence of 113 products registered for commercialization in Brazil. It was found that, despite the increased consumption due to diseases caused by bites from Aedes aegypti mosquitoes, most repellents marketed have as active ingredients the substances DEET, Icaridin or IR3535, not resulting in toxic reactions relevant to the population, since these substances are of low toxicity or non- toxic, as is the case of IR3535. It is necessary to consider that the use of these products should strictly follow the manufacturers' guidelines available on the packaging labels regarding application, reapplication, frequency and specific use for children, pregnant and lactating women. With regard to efficacy, Icaridin is more effective than IR3535 when considering the factors protection time versus concentration of the active ingredient. However, Icaridin, in some cases, may present moderate toxicity, while IR3535 is non- toxic. It is also observed that, even in this scenario, DEET is the most marketed and widely studied in the country.

artículo tuvo como objetivo evaluar los efectos del uso de repelentes en la población brasileña. Para alcanzar el objetivo propuesto, se utilizaron las metodologías de revisión bibliográfica e investigación documental con ANVISA sobre repelentes registrados y comercializados en Brasil. De acuerdo con el CDR nº 7 de 2015 de ANVISA, los repelentes se clasifican como productos de Grado 2, compuesto por Productos de Higiene Personal, Cosméticos y Perfumes. En esta categoría, se constató la existencia de 113 productos registrados para comercialización en Brasil. Se constató que, a pesar del aumento del consumo debido a las enfermedades causadas por picaduras de mosquitos Aedes aegypti, la mayoría de los repelentes comercializados tienen como principios activos las sustancias DEET, Icaridina o IR3535, no resultando en reacciones tóxicas relevantes para la población, ya que estas sustancias son de baja toxicidad o no tóxicas, como es el caso del IR3535. Es necesario considerar que el uso de estos productos debe seguir estrictamente las directrices de los fabricantes disponibles en las etiquetas de los envases en cuanto a aplicación, reaplicación, frecuencia y uso específico para niños, mujeres embarazadas y lactantes. En cuanto a la eficacia, la Icaridina es más eficaz que el IR3535 si se consideran los factores tiempo de protección frente a concentración del principio activo. Sin embargo, la Icaridina, en algunos casos, puede presentar una toxicidad moderada, mientras que el IR3535 no es tóxico. También se observa que, incluso en este escenario, el DEET es el más comercializado y ampliamente estudiado en el país.

Effects of environmentally relevant concentrations of atrazine and glyphosate herbicides, isolated and in mixture, on two generation of the freshwater microcrustacean Daphnia magna.

The herbicides atrazine and glyphosate are used worldwide and their excessive usage results in the frequent presence of these pesticides in environmental compartments. We evaluated the effects of environmentally relevant concentrations of analytical standards and commercial formulations of atrazine (2 µg L-1) and glyphosate (65 µg L-1), isolated and in mixture (2 + 65 µg L-1) on the microcrustacean Daphnia magna. Through chronic exposure (21 days) of two generations, we observed effects on survival, reproductive capacity and responses of the antioxidant defense system (catalase) and biotransformation system (glutathione S-transferase). The survival of organisms was affected in the second generation (F1) with a mortality of 17% in the mixture of commercial formulations treatments. In the evaluation of the first generation (F0) we observed only effects on sexual maturation of organisms, while in the F1, changes were observed in all parameters evaluated. A statistical difference (p < 0.05) was also observed between the analytical standards and the commercial formulations for all parameters evaluated, indicating that other components present in the formulations can change the toxicity of products. We suggest that atrazine can modulate toxicity when mixed with glyphosate, as the standard analytical atrazine and mixture of analytical standards results were similar in most parameters. Given the difficulty in estimating effects of mixtures and considering that various stressors are found in the environment, our results support the need to carry out long-term studies and, above all, to verify what are the impacts across generations, so that the toxicity of products is not underestimated. Graphical abstract.

Evaluación del desempeño de los métodos analíticos aplicados en el diclofenaco sódico 100 mg retard de producción nacional / Evaluation of the performance of the analytical methods applied to Cuban-made 100mg retard sodium diclofenac

Introducción: el diclofenaco sódico es un derivado del ácido fenilácetico y pertenece al grupo de los antinflamatorios no esteroideos con propiedades antinflamatorios, analgésicas y antipiréticas pronunciadas. En la Farmacopea de los Estados Unidos (USP 36, 2013) aparece reportado los métodos analíticos para el control de calidad del diclofenaco sódico en el ingrediente farmacéutico activo y en las tabletas. Objetivos: evaluar el desempeño de los métodos analíticos que se emplean en el control de la calidad de cuantificación y los estudios de estabilidad del ingrediente farmacéutico activo; así como los ensayos de disolución de las tabletas de diclofenaco sódico 100 mg retard de producción nacional. Métodos: en la evaluación del desempeño del método analítico potenciométrico para la cuantificación del ingrediente farmacéutico activo se analizaron los parámetros de linealidad y de precisión (repetibilidad y precisión intermedia). Para el método cromatográfico aplicable a la cuantificación del ingrediente farmacéutico activo en el producto terminado se analizaron los parámetros de especificidad, precisión y exactitud. En el método espectrofotométrico empleado en el ensayo de disolución se tuvo en cuenta la especificidad, la precisión, la linealidad, la influencia del filtrado y la estabilidad de las soluciones analíticas. Resultados: la evaluación del desempeño realizada a los diferentes métodos analíticos, fueron satisfactorias, demostrando que son lineales, precisos y específicos en el rango de concentraciones estudiadas. Conclusiones: se demostró la confiabilidad de los métodos empleados en el control de la calidad y los estudios de estabilidad del ingrediente farmacéutico activo y de las tabletas de diclofenaco sódico 100 mg retard de producción nacional(AU)

Introduction: sodium dicloflenac is a phenylacetic acid derivate included in the non-steroidal anti-inflammatory group, with marked analgesic and antipyretic properties. The US Pharmacopeia (USP 36, 2013) reports the analytical methods for the quality control of sodium diclofenac in the active ingredient and in tablets. Objectives: to evaluate the performance of the analytical methods used in the quality control of quantitation and the stability studies of the active ingredient as well as the dissolution tests of the Cuban-made 100 mg retard sodium diclofenac. Methods: the evaluation of the performance of the potentiometric analytical method for quantitation of the active ingredient analyzed the parameters called linearity and precision (repeatability and intermediate precision). For the chromatographic method applicable to quantitation of the active ingredient in the finished product, parameters such as specificity, precision and accuracy were analyzed. The spectrophotometric method used in the dissolution test took into account specificity, precision, linearity, filtering effect and stability of the analytical solutions. Results: the evaluation of the performance of the different analytical methods was satisfactory and they proved to be linear, precise and specific in the range of studied concentrations. Conclusions: the reliability of the methods for the quality control and of the stability studies of the active ingredient and of Cuban-made 100 mg retard sodium diclofenac was demonstrated(AU)

Efficacy of essential oil of Piper aduncum against nymphs and adults of Diaphorina citri.

BACKGROUND: Insecticide application is the main way to control Diaphorina citri. However, it causes environmental contamination, has a negative impact on beneficial organisms and leads to psyllid resistance. The essential oil of Piper aduncum has low toxicity towards the environment and contains dillapiol, which has proven to be effective against several crop pests. Here, we studied its efficacy against nymphs and adults of D. citri under laboratory conditions. Oils with three concentrations of dillapiol (69.3, 79.9 and 85.4%) at 0.5, 0.75 and 1.0% dilutions plus 0.025% adjuvant were tested. RESULTS: All treatments caused 90-100% mortality in nymphs. Topical treatments with oil containing 79.9 and 85.4% dillapiol at 0.75% and 1% dilutions were effective (mortality ≥80%) in adults. However, the essential oil showed no residual activity against adults (mortality ≤30%). CONCLUSIONS: Dillapiol-rich oil is a promising compound for D. citri control. © 2015 Society of Chemical Industry.