Abstract The aim was to evaluate the effect of 2% grape seed extract (GSE) containing phosphoric acid (PhA) on the bond strength to enamel and dentin. The control group was 37% PhA. The following three PhA formulations with 2% GSE and 20% ethanol were obtained: GSE5 = 5% PhA; GSE10 = 10% PhA; and GSE20 = 20% PhA. The enamel and dentin surfaces of molars were etched with the acid solutions, followed by Scotchbond Multi-Purpose adhesive and composite resin application. The tensile bond strength (TBS) test evaluated the bond to enamel after 24 h, and the microtensile bond strength (μTBS) test evaluated the bond to dentin after 24 h and 12-month water storage. Etched enamel and dentin were observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM), respectively. The TBS data were submitted to one-way ANOVA, while µTBS data were submitted to two-way ANOVA and Tukey’s test (α = 0.05). The TBS (MPa) to enamel did not significantly differ among the control (48.1 ± 15.7), GSE5 (46.1 ± 9.6), GSE10 (49.8 ± 13.6) and GSE20 (44.1 ± 11.9) groups (p = 0.537). The µTBS (MPa) to dentin of the control (28.4 ± 14.4) and GSE20 (24.1 ± 8.1) groups were significantly higher than those of the GSE5 (16.8 ± 7.4) and GSE10 (17.5 ± 6.6) groups at 24 h (p < 0.006). After 12-month storage, only GSE5 (21.0 ± 7.8) and GSE10 (17.6 ± 8.0) did not show significantly decreased μTBS (p > 0.145). SEM micrographs showed a shallower enamel etching pattern for GSE5. AFM images showed the formation of collagenous globular structures for GSE5 and GSE10. The different acid solutions did not influence the TBS to enamel, and the µTBS to dentin was stable over time when dentin was etched with GSE5 and GSE10.

O gene CYP2C19 apresenta polimorfismo genético, com impacto importante na farmacocinética de diversos fármacos de importância clínica. O objetivo deste estudo foi avaliar a correlação entre genótipo e fenótipo de CYP2C19 em um grupo de 38 voluntários brasileiros, avaliando a capacidade de predição do fenótipo a partir de testes de genotipagem. Para a fenotipagem, utilizou-se omeprazol (OME) como fármaco-sonda para CYP2C19, empregando sua razão metabólica de hidroxilação como indicador fenotípico. Amostras de sangue foram coletadas antes e três horas após a administração oral de 20mg do fármaco. As concentrações plasmáticas de OME e seu metabólito foram determinadas por cromatografia líquida de alta eficiência. A genotipagem de CYP2C19 foi realizada através de ensaio baseado na reação em cadeia da polimerase em tempo real, identificando os alelos *1 (completamente funcional),*2 e *3 (nulos). Pela fenotipagem foi possível estimar a presença de 3 metabolizadores lentos, 34 rápidos e 1 ultra-rápido; enquanto pela genotipagem foi determinada a presença de 4 metabolizadores lentos, 23 rápidos e 11 intermediários. Os grupos de voluntários classificados de acordo com o número de alelos ativos apresentaram diferenças significativas entre as razões metabólicas de hidroxilação de omeprazol. Entretanto, indivíduos com o mesmo genótipo apresentaram fenótipos diferentes. Desta forma, a fenotipagem apresenta-se como alternativa mais promissora para a individualização das doses de fármacos substratos de CYP2C19.

The CYP2C19 gene presents polymorphism affecting the pharmacokinetics of several drugs of clinical importance. The purpose of this study was to investigate the correlation between CYP2C19 genotype and metabolic phenotype in a group of 38 Brazilian volunteers, evaluating the phenotype prediction capacity of the genotyping procedure. For CYP2C19 phenotyping, omeprazole was used as the probe drug, using the hydroxylation metabolic ratio as the phenotypic indicator. Venous blood samples were drawn before and three hours after an oral administration of 20 mg omeprazole. The plasma concentrations of omeprazole and hydroxy-omeprazole were determined by high performance liquid chromatography. The genotyping assay was carried out using a Real-Time-PCR-based assay, identifying the alleles *1 (completely functional), *2, *3 and *4 (null). The phenotyping procedure estimated the presence of 4 poor, 34 extensive and 1 ultra-extensive metabolizer. The genotyping identified 4 poor, 23 extensive and 11 intensive metabolizers. The groups of volunteers classified according to the number of active alleles of CYP2C19 had significant differences in the metabolic ratios of omeprazole hydroxylation. However, volunteers exhibiting the same number of active alleles presented different phenotypes. Therefore, the phenotyping of CYP2C19 is a more promising alternative to dose individualization of CYP2C19 substrate drugs.

Foi desenvolvido e validado um método simples e rápido, empregando CLAE-DAD, para a determinação simultânea de amitriptilina, nortriptilina, E-10-hidroxiamitriptilina, Z-10-hidroxiamitriptilina, E-10-hidroxinortriptilina, Z-10-hidroxinortriptilina e desmetilnortriptilina em amostras de plasma humano. O método utiliza extração líquido-líquido em duas etapas e separação isocrática em fase reversa. A precisão apresentou D.P.R. % menor que 12.1% e a precisão esteve na faixa entre 93,1 e 102,5%. O limite de detecção foi 5 ng mL-1 para todos os analitos. Foram avaliadas razões metabólicas de desmetilação da amitriptilina em indivíduos genotipados para CYP2C19, com nítidas diferenças entre os valores obtidos nos voluntários com zero ou dois alelos ativos. O método é adequado para o monitoramento terapêutico de pacientes em terapia com amitriptilina, permitindo também a indicação da atividade de CYP2C19.

A simple and sensitive HPLC-DAD method for the simultaneous determination of amitriptyline, nortriptyline, E-10-hydroxyamitriptyline, Z-10-hydroxyamitriptyline, E-10-hydroxynortriptyline, Z-10-hydroxynortriptyline and desmethylnortriptyline in human plasma samples was developed and validated. The method employs a two step liquid-liquid extraction and a reversed phase separation with isocratic elution. Precision assays showed R.S.D % lower than 12.1% and accuracy was in the range of 93.1 to 102.5%. Lowest Limit of detection was 5 ng mL-1 for all analytes. Metabolic ratios of amitriptyline demethylation were evaluated in individuals genotyped for CYP2C19, with clear differences between volunteers with zero or two active alleles. The method is suitable for therapeutic drug monitoring of patients under amitriptyline treatment, also allowing the indication of CYP2C19 activity.

Foram desenvolvidas as emulsões NI (não-iônica) e CL (cristal líquido) e avaliados os parâmetros reológicos, assim como o efeito hidratante das emulsões NI e CL em mulheres, com faixa etária de 20 ± 2 anos e da emulsão NI em mulheres com faixa etária de 70 ± 7 anos. Os resultados demonstraram adequada estabilidade das emulsões e comportamento pseudoplástico, além de tixotropia aparente. Para a emulsão NI, foi alcançado o melhor perfil reológico com menor ponto de fluidez (13,57 ± 3,19 Pa) e maior espalhabilidade (4,99 ± 0,54 mm²/g). Não houve diferença significativa de hidratação dos produtos em mulheres com faixa etária de 20 ± 2 anos da emulsão NI e CL (16,0 ± 5,1%, 14,2 ± 5,5%). No entanto, a hidratação do grupo de mulheres com faixa etária de 70 ± 7 anos foi de 13,1 ± 5,6% para a emulsão NI. Esse resultado demonstra hidratação significativamente menor nesse grupo, quando comparada ao grupo com menor faixa etária. Dessa forma, foi comprovada para esse estudo a importância da avaliação reológica como fator de seleção entre formulações cosméticas semelhantes. Além disso, observou-se a relevância da seleção etária para a avaliação da hidratação cutânea de cosméticos.

NI (nonionic) and LC (liquid crystal) emulsions were developed, and their rheological parameters were evaluated. Also, the hydrating effect of NI and LC emulsions was tested among women with 20 ± 2 years, as well as NI emulsions among women with 70 ± 7 years of age. The results showed that the emulsions were stable and they had a pseudoplastic behavior and apparent thixotropy. The data revealed the best rheological profile of the NI emulsion with the lowest pour point (13.57 ± 3.19 Pa) and the highest spreadability (4.99 ± 0.54 mm²/g). There was no significant difference in hydration between NI and LC emulsions (16.0 ± 5.1%; 14.2 ± 5.5%) among younger women. However, hydration among elderly women was of 13.1 ± 5.6% for NI emulsion, revealing that it was significantly lower in this group when compared to the younger one. These data revealed the importance of rheological evaluation as a factor of choice among similar cosmetic formulations. Age bracket selection also proved to be very important in the assessment of skin hydration by cosmetic products.

In spite of the availability of large databases of chromatographic data on several standardized systems, one major task in systematic toxicological analysis remains, namely how to handle the experimental data and retrieve data from the large available databases in a meaningful and productive way. To achieve this purpose, our group proposed an Internet-based tool using previously published STA databases, which interlaboratorial reproducibility tests have already evaluated. The developed software has the capability to calculate corrected chromatographic parameters, after the input of data obtained with standard mixtures of calibrators, and search the databases, currently incorporating TLC, color reactions, GC and HPLC data. At the end of the process, a list with candidate substances and their similarity indexes is presented.