OS CASOS “GOMES LUND” E “HERZOG” NA DITADURA MILITAR: dialógo entre cortes ou reforço da supremacia judicial interna?

A partir da ideia de um diálogo a ser exercido entre o âmbito interno e externo, especialmente entre o Supremo Tribunal Federal (STF) e a Corte Interamericana de Direitos Humanos (Corte IDH), em se tratando do Brasil, questiona-se: diante dos casos “Gomes Lund” e “Herzog”, versus Brasil, é possível afirmar a (in)existência de uma abertura ao diálogo jurisdicional por parte do STF, com relação à Corte IDH? Assim, utiliza-se o método hipotético-dedutivo e objetiva-se, num primeiro momento, abordar a lógica de funcionamento do Sistema Interamericano, para, então, apontar os aspectos essenciais referentes às teorias que sustentam diálogos jurisdicionais, e, por fim, analisar se há, ou não, uma abertura ao diálogo com a Corte IDH, por parte do STF, a partir dos casos “Gomes Lund” e “Herzog”. É possível afirmar, diante da análise realizada, que o STF vem reforçando uma supremacia judicial interna, não mostrando-se aberto ao diálogo jurisdicional, sustentado argumentativamente

Enhanced solar driven photocatalytic removal of antibiotics from aquaculture effluents by TiO2/carbon quantum dot composites

Aquaculture exploitation is associated with the consumption of antibiotics, such as sulfadiazine (SDZ), sulfamethoxazole (SMX) and trimethoprim (TMP), the latter two being also vastly used to treat bacterial infections in humans. Consequently, and given that aquaculture wastewater treatments are not actually designed for the removal of antibiotics, they are ubiquitous in aquaculture effluents, which sets the risk of bacterial resistance. To face the need for an efficient and sustainable treatment to remove these antibiotics from the referred effluents, carbon quantum dots (CQDs) were produced, incorporated into titanium dioxide (TiO2), and evaluated for solar driven photodegradation of SDZ, SMX and TMP. Eleven different materials were synthesized and tested for their photocatalytic activity in phosphate buffer solution (PBS) and synthetic sea salts (SSS), used as synthetic matrices to simulate fresh and brackish water, respectively. Upon selection of the most efficient photocatalyst for each antibiotic and matrix, kinetic results demonstrated that its use allowed for remarkable reductions of SDZ, SMX and TMP half-life times (t1/2) in both matrices (between 19 and 68 times). Therefore, the application of the here synthesized photocatalysts for the advanced treatment of aquaculture effluents is promising, allowing for a green solar driven removal of antibiotics.publishe

Targeting p53 for melanoma treatment: counteracting tumour proliferation, dissemination and therapeutic resistance

Melanoma is the deadliest form of skin cancer, primarily due to its high metastatic propensity and therapeutic resistance in advanced stages. The frequent inactivation of the p53 tumour suppressor protein in melanomagenesis may predict promising outcomes for p53 activators in melanoma therapy. Herein, we aimed to investigate the antitumor potential of the p53-activating agent SLMP53-2 against melanoma. Two- and three-dimensional cell cultures and xenograft mouse models were used to unveil the antitumor activity and the underlying molecular mechanism of SLMP53-2 in melanoma. SLMP53-2 inhibited the growth of human melanoma cells in a p53-dependent manner through induction of cell cycle arrest and apoptosis. Notably, SLMP53-2 induced p53 stabilization by disrupting the p53–MDM2 interaction, enhancing p53 transcriptional activity. It also promoted the expression of p53-regulated microRNAs (miRNAs), including miR-145 and miR-23a. Moreover, it displayed anti-invasive and antimigratory properties in melanoma cells by inhibiting the epithelial-to-mesenchymal transition (EMT), angiogenesis and extracellular lactate production. Importantly, SLMP53-2 did not induce resistance in melanoma cells. Additionally, it synergized with vemurafenib, dacarbazine and cisplatin, and resensitized vemurafenib-resistant cells. SLMP53-2 also exhibited antitumor activity in human melanoma xenograft mouse models by repressing cell proliferation and EMT while stimulating apoptosis. This work discloses the p53-activating agent SLMP53-2 which has promising therapeutic potential in advanced melanoma, either as a single agent or in combination therapy. By targeting p53, SLMP53-2 may counteract major features of melanoma aggressiveness.This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through LAQV/REQUIMTE (UID/QUI/50006/2020), iMed.ULisboa (UIDB/04138/2020), and PTDC/QUIQOR/29664/2017, PTDC/MEC-ONC/32018/2017. We thank FCT for the fellowships SFRH/BD/ 128673/2017 (J. Loureiro), 2020.04613.BD (J. Calheiros), PD/BD/143126/2019 (V. Barcherini)

Método analítico para a determinação de meloxicam em plasma humano por cromatografia líquida de alta eficiência (CLAE)

A simple, rapid and specific high-performance liquid cromatographic (HPLC) method was developed and validated to estimate meloxicam (COX-2 inhibitor) levels in human plasma. Piroxicam was used as internal standard. Reversed phase chromatography was conducted using a Synergi RP-MAX (150 x 4.6 mm) column at 30 ºC and a mobile phase of acetonitrile and 0.025 mol/L pH 4,5 phosphate buffer (40:60, v/v), at a flow rate of 1mL/min. Analytes were detected at 364 nm. Plasma samples were acidified with 1 mol/L hydrochloric acid and extracted with tert-butyl methyl ether, evaporated to dryness, reconstituted in 250 mL of mobile phase and injected in the column. The retention time of meloxicam and piroxicam were 3.35 and 4.19 minutes, respectively. This method showed to be linear in the range of 50 - 4500 ng/mL (R² = 0.9995), a LOQ of 50 ng/mL and accuracy of 114%. The analytical method showed suitable specificity, sensitivity, linearity, precision and accuracy, and can be used in bioequivalence or pharmacokinetics studies involving meloxicam.Desenvolveu-se e validou-se método analítico simples, rápido e específico para quantificação de meloxicam (inibidor da COX-2) em plasma humano através da cromatografia líquida de alta eficiência, para aplicação em estudos de bioequivalência. Piroxicam foi utilizado como padrão interno. Empregou-se cromatografia em fase reversa com coluna modelo Synergi RP-MAX (150 x 4,6 mm), à temperatura de 30 ºC e fase móvel constituída por mistura de acetonitrila e tampão fosfato 0,025 mol/L pH 4,5 (40:60, v/v), a um fluxo de 1,0 mL/min. Os analitos foram detectados por UV a 364 nm. As amostras de plasma foram acidificadas com ácido clorídrico 1 mol/L, extraídas utilizando-se éter terc-butil metílico e, após filtração e secagem, o resíduo foi reconstituído em 250 mL de fase móvel para injeção em CLAE. Os tempos de retenção para meloxicam (padrão) e piroxicam (padrão interno) foram 3,35 e 4,19 minutos, respectivamente. Este método apresentou linearidade na faixa de concentração entre 50-4000 ng/mL (R² = 0,9995), com limite de quantificação inferior de 50 ng/mL e exatidão de 114%. O método analítico desenvolvido neste trabalho demonstrou especificidade, linearidade, precisão e exatidão adequadas, permitindo sua aplicação em ensaios de bioequivalência