RESUMO
This study aimed to assess whether perinatal exposure to propiconazole (PRO), glyphosate (GLY) or their mixture (PROGLY) alters key endocrine pathways and the development of the male rat mammary gland. To this end, pregnant rats were orally exposed to vehicle, PRO, GLY, or a mixture of PRO and GLY from gestation day 9 until weaning. Male offspring were euthanized on postnatal day (PND) 21 and PND60. On PND21, GLY-exposed rats showed reduced mammary epithelial cell proliferation, whereas PRO-exposed ones showed increased ductal p-Erk1/2 expression without histomorphological alterations. On PND60, GLY-exposed rats showed reduced mammary gland area and estrogen receptor alpha expression and increased aromatase expression, whereas PRO-exposed ones showed enhanced lobuloalveolar development and increased lobular hyperplasia. However, PROGLY did not modify any of the endpoints evaluated. In summary, PRO and GLY modified the expression of key molecules and the development of the male mammary gland individually but not together.
Assuntos
Efeitos Tardios da Exposição Pré-Natal , Triazóis , Gravidez , Feminino , Ratos , Animais , Masculino , Humanos , Triazóis/toxicidade , Glicina/toxicidade , Glicina/metabolismo , Hiperplasia/metabolismo , Glândulas Mamárias Animais , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , GlifosatoRESUMO
Higher-order data generation implies some automation challenges, which are mainly related to the hidden programming languages and electronic details of the equipment. When techniques and/or equipment hyphenation are the key to obtaining higher-order data, the required simultaneous control of them demands funds for new hardware, software, and licenses, in addition to very skilled operators. In this work, we present Design of Inputs-Outputs with Sikuli (DIOS), a free and open-source code program that provides a general framework for the design of automated experimental procedures without prior knowledge of programming or electronics. Basically, instruments and devices are considered as nodes in a network, and every node is associated both with physical and virtual inputs and outputs. Virtual components, such as graphical user interfaces (GUIs) of equipment, are handled by means of image recognition tools provided by Sikuli scripting language, while handling of their physical counterparts is achieved using an adapted open-source three-dimensional (3D) printer. Two previously reported experiments of our research group, related to fluorescence matrices derived from kinetics and high-performance liquid chromatography, were adapted to be carried out in a more automated fashion. Satisfactory results, in terms of analytical performance, were obtained. Similarly, advantages derived from open-source tools assistance could be appreciated, mainly in terms of lesser intervention of operators and cost savings.
RESUMO
A study regarding the acquisition and analytical utilization of four-way data acquired by monitoring excitation-emission fluorescence matrices at different elution time points in a fast HPLC procedure is presented. The data were modeled with three well-known algorithms: PARAFAC, U-PLS/RTL and MCR-ALS, the latter conveniently adapted to model third-order data. The second-order advantage was exploited when analyzing samples containing uncalibrated components. The best results were furnished with the algorithm U-PLS/RTL. This fact is indicative of both no peak time shifts occurrence among samples and high colinearity among spectra. Besides, this latent-variable structured algorithm is capable of better handle the need of achieving high sensitivity for the analysis of one of the analytes. In addition, a significant enhancement in both predictions and analytical figures of merit was observed for carbendazim, thiabendazole, fuberidazole, carbofuran, carbaryl and 1-naphtol, when going from second- to third-order data. LODs obtained were ranged between 0.02 and 2.4µgL(-1).
Assuntos
Sucos de Frutas e Vegetais , Calibragem , Carbaril , Cromatografia Líquida de Alta Pressão , Praguicidas , Espectrometria de FluorescênciaRESUMO
Methotrexate (MTX) is an antineoplastic drug, and due to its high toxicity, the therapeutic drug monitoring is strictly conducted in the clinical practice. The chemometric optimization and validation of a high performance liquid chromatography (HPLC) method using core-shell particles is presented for the determination of MTX in plasma during therapeutic monitoring. Experimental design and response surface methodology (RSM) were applied for the optimization of the chromatographic system and the analyte extraction step. A Poroshell 120 EC-C18 (3.0 mm×75 mm, 2.7 µm) column was used to obtain a fast and efficient separation in a complete run time of 4 min. The optimum conditions for the chromatographic system resulted in a mobile phase consisting of acetic acid/sodium acetate buffer solution (85.0 mM, pH=4.00) and 11.2% of acetonitrile at a flow rate of 0.4 mL/min. Selectivity, linearity, accuracy and precision were demonstrated in a range of 0.10-6.0 µM of MTX. The application of the optimized method required only 150 µL of patient plasma and a low consumption of solvent to provide rapid results.
RESUMO
An efficient generic static headspace gas chromatography (HSGC) method was developed, optimized and validated for the routine determination of several residual solvents (RS) in drug substance, using a strategy with two sets of calibration. Dimethylsulfoxide (DMSO) was selected as the sample diluent and internal standards were used to minimize signal variations due to the preparative step. A gas chromatograph from Agilent Model 6890 equipped with flame ionization detector (FID) and a DB-624 (30 m×0.53 mm i.d., 3.00 µm film thickness) column was used. The inlet split ratio was 5:1. The influencing factors in the chromatographic separation of the analytes were determined through a fractional factorial experimental design. Significant variables: the initial temperature (IT), the final temperature (FT) of the oven and the carrier gas flow rate (F) were optimized using a central composite design. Response transformation and desirability function were applied to find out the optimal combination of the chromatographic variables to achieve an adequate resolution of the analytes and short analysis time. These conditions were 30 °C for IT, 158 °C for FT and 1.90 mL/min for F. The method was proven to be accurate, linear in a wide range and very sensitive for the analyzed solvents through a comprehensive validation according to the ICH guidelines.