Electrochemical oxidation of tamoxifen revisited

Tamoxifen is a selective estrogen receptor modulator that is used as an adjuvant and/or chemotherapeutic agent for the treatment of all stages of hormone-dependent breast cancer. Currently there is a deep interest in the study of tamoxifen biotransformation and identification of metabolites since they can significantly contribute to the overall pharmacological or adverse effects of the drug. Accordingly, the study of the electrochemical behavior of tamoxifen in aqueous solution is reported. To clarify the occurring oxidative process and to assess the influence of the functional groups on the oxidation mechanism, the voltammetric assessment was extended to the study of tamoxifen’s analogues (E)-tamoxifen and dihydrotamoxifen, and to its main phase I oxidative metabolite, N-desmethyl tamoxifen. The data found shows that the oxidative processes occurring in tamoxifen are essentially related with the two chemical moieties present in the molecule: the substituted aromatic nucleus and the tertiary amine group. Moreover, the results obtained suggest that the ethylenic linkage is not critical for tamoxifen’s oxidation although it could play an important role in the course of the oxidation process. These results could contribute to highlight some remaining questions regarding tamoxifen’s metabolic behavior and to the development of new analytical strategies, based on electrochemical approaches.

Wine and grape polyphenols — a chemical perspective

Phenolic compounds constitute a diverse group of secondary metabolites which are present in both grapes and wine. The phenolic content and composition of grape processed products (wine) are greatly influenced by the technological practice to which grapes are exposed. During the handling and maturation of the grapes several chemical changes may occur with the appearance of new compounds and/or disappearance of others, and consequent modification of the characteristic ratios of the total phenolic content as well as of their qualitative and quantitative profile. The non-volatile phenolic qualitative composition of grapes and wines, the biosynthetic relationships between these compounds, and the most relevant chemical changes occurring during processing and storage will be highlighted in this review.

Numerical and experimental analyses of biocomposites reinforced with natural fibres

n the last decades the biocomposites have been widely used in the construction, automobile and aerospace industries. Not only the interface transition zone (ITZ) but also the heterogeneity of natural fibres affects the mechanical behaviour of these composites. This work focuses on the numerical and experimental analyses of a polymeric composite fabricated with epoxy resin and unidirectional sisal and banana fibres. A three-dimensional model was set to analyze the composites using the elastic properties of the individual phases. In addition, a two-dimensional model was set taking into account the effective composite properties obtained by micromechanical models. A tensile testing was performed to validate the numerical analyses and evaluating the interface condition of the constitutive phases.

SPE-LC-FD Determination of Polycyclic Aromatic Hydrocarbon Monohydroxy Derivatives in Cephalopods

A new analytical methodology, based on liquid chromatography with fluorescence detection (LC-FD), after extraction, enzymatic hydrolysis, and solid-phase extraction (SPE) through Oasis HLB cartridges, was developed and validated for the simultaneous determination of three monohydroxy derivatives of polycyclic aromatic hydrocarbons (PAHs). The optimized analytical method is sensitive, accurate, and precise, with recoveries between 62 and 110% and limits of detection of 227, 9, and 45 ng/g for 1-hydroxynaphthalene, 2-hydroxyfluorene, and 1-hydroxypyrene, respectively. Their levels were estimated in different cephalopod matrices (edible tissues and hemolymph). The methodology was applied to samples of the major cephalopod species consumed worldwide. Of the 18 samples analyzed, 39% were contaminated with 1-hydroxynaphthalene, which was the only PAH metabolite detected. Its concentration ranged from 786 to 1145 ng/g. This highly sensitive and specific method allows the identification and quantitation of PAH metabolites in forthcoming food safety and environmental monitoring programs.

A penhora e os seus efeitos registais

Dissertação de Mestrado em Solicitadoria

Picocyanobacteria From a Clade Of Marine Cyanobium Revealed Bioactive Potential Against Microalgae, Bacteria, And Marine

The production of bioactive compounds either toxic or with pharmacological applications by cyanobacteria is well established. However, picoplanktonic forms within this group of organisms have rarely been studied in this context. In this study, the toxicological potential of picocyanobacteria from a clade of marine Cyanobium strains isolated from the Portuguese coast was examined using different biological models. First, strains were identified by applying morphological and molecular approaches and cultured under lab conditions. A crude extract and three fractions reflecting a preliminary segregation of lipophilic metabolites were tested for toxicity with the marine microalga Nannochloropsis sp., the bacteria Pseudomonas sp., the brine shrimp Artemia salina, and fertilized eggs of the sea urchin Paracentrotus lividus. No significant apparent adverse effects were noted against Artemia salina. However, significant adverse effects were found in all other assays, with an inhibition of Nannochloropsis sp. and Pseudomonas sp. growth and marked reduction in Paracentrotus lividus larvae length. The results obtained indicated that Cyanobium genus may serve as a potential source of interesting bioactive compounds and emphasize the importance of also studying smaller picoplanktonic fractions of marine cyanobacteria.

Cytotoxicity in L929 fibroblasts and inhibition of herpes simplex virus type 1 Kupka by estuarine cyanobacteria extracts

The cyanobacteria are known to be a rich source of metabolites with a variety of biological activities in different biological systems. In the present work, the bioactivity of aqueous and organic (methanolic and hexane) crude extracts of cyanobacteria isolated from estuarine ecosystems was studied using different bioassays. The assessment of DNA damage on the SOS gene repair region of mutant PQ37 strain of Escherichia coli was performed. Antiviral activity was evaluated against influenza virus, HRV-2, CVB3 and HSV-1 viruses using crystal violet dye uptake on HeLa, MDCK and GMK cell lines. Cytotoxicity evaluation was performed with L929 fibroblasts by MTT assay. Of a total of 18 cyanobacterial isolates studied, only the crude methanolic extract of LEGE 06078 proved to be genotoxic (IF > 1.5) in a dose-dependent manner and other four were putative candidates to induce DNA damage. Furthermore, the crude aqueous extract of LEGE 07085 showed anti- herpes type 1 activity (IC50 = 174.10 μg dry extract mL−1) while not presenting any cytotoxic activity against GMK cell lines. Of the 54 cyanobacterial extracts tested, only the crude methanolic and hexane ones showed impair on metabolic activity of L929 fibroblasts after long exposure (48–72 h). The inhibition of HSV-1 and the strong cytotoxicity against L929 cells observed emphasizes the importance of evaluating the impact of those estuarine cyanobacteria on aquatic ecosystem and on human health. The data also point out their potential application in HSV-1 treatment and pharmacological interest.

A new biomimetic sensor for detecting carnitine, a potential biomarker in ovarian cancer

1st ASPIC International Congress

Discrete fractional order system vibrations

A theory of free vibrations of discrete fractional order (FO) systems with a finite number of degrees of freedom (dof) is developed. A FO system with a finite number of dof is defined by means of three matrices: mass inertia, system rigidity and FO elements. By adopting a matrix formulation, a mathematical description of FO discrete system free vibrations is determined in the form of coupled fractional order differential equations (FODE). The corresponding solutions in analytical form, for the special case of the matrix of FO properties elements, are determined and expressed as a polynomial series along time. For the eigen characteristic numbers, the system eigen main coordinates and the independent eigen FO modes are determined. A generalized function of visoelastic creep FO dissipation of energy and generalized forces of system with no ideal visoelastic creep FO dissipation of energy for generalized coordinates are formulated. Extended Lagrange FODE of second kind, for FO system dynamics, are also introduced. Two examples of FO chain systems are analyzed and the corresponding eigen characteristic numbers determined. It is shown that the oscillatory phenomena of a FO mechanical chain have analogies to electrical FO circuits. A FO electrical resistor is introduced and its constitutive voltage–current is formulated. Also a function of thermal energy FO dissipation of a FO electrical relation is discussed.

Serpentine bacteria influence metal translocation and bioconcentration of Brassica juncea and Ricinus communis grown in multi-metal polluted soils

The aim of this study was to assess the effects of inoculation of rhizosphere or endophytic bacteria (Psychrobacter sp. SRS8 and Pseudomonas sp. A3R3, respectively) isolated from a serpentine environment on the plant growth and the translocation and accumulation of Ni, Zn, and Fe by Brassica juncea and Ricinus communis on a multi-metal polluted serpentine soil (SS). Field collected SS was diluted to 0, 25, 50, and 75% with pristine soil in order to obtain a range of heavy metal concentrations and used in microcosm experiments. Regardless of inoculation with bacteria, the biomass of both plant species decreased with increase of the proportion of SS. Inoculation of plants with bacteria significantly increased the plant biomass and the heavy metal accumulation compared with non-inoculated control in the presence of different proportion of SS, which was attributed to the production of plant growth promoting and/or metal mobilizing metabolites by bacteria. However, SRS8 showed a maximum increase in the biomass of the test plants grown even in the treatment of 75% SS. In turn, A3R3 showed maximum effects on the accumulation of heavy metals in both plants. Regardless of inoculation of bacteria and proportion of SS, both plant species exhibited low values of bioconcentration factor (<1) for Ni and Fe. The inoculation of both bacterial strains significantly increased the translocation factor (TF) of Ni while decreasing the TF of Zn in both plant species. Besides this contrasting effect, the TFs of all metals were <1, indicating that all studied bacteria–plant combinations are suitable for phytostabilization. This study demonstrates that the bacterial isolates A3R3 and SRS8 improved the growth of B. juncea and R. communis in SS soils and have a great potential to be used as inoculants in phytostabilization scenarios of multi-metal contaminated soils.

Elétrodo de pasta de carbono molecularmente impresso para deteção voltamétrica de Furazolidona

A furazolidona é uma substância ativa do medicamento Giarlam que contém um espetro anti-bacteriano relativamente amplo e que é frequentemente usado para tratar certas doenças bacterianas e protozoárias no homem. A maioria dos fármacos exige uma dosagem que garanta os níveis de segurança e eficácia de atuação. A necessidade de dosear os medicamentos e os seus metabólitos exige o desenvolvimento constante de métodos analíticos eficientes. Neste trabalho desenvolveu-se um novo sensor eletroquímico para a deteção da furazolidona, baseado num elétrodo de pasta de carbono modificado com um polímero molecularmente impresso. A procura de novos materiais que permitam uma melhor seletividade e sensibilidade aos sistemas de deteção é especialmente importante no desenvolvimento de métodos analíticos. Os polímeros molecularmente impressos enquadram-se nesse perfil e o seu uso tem vindo a ser cada vez mais frequente como ferramenta importante em química analítica. Assim, sintetizou-se um polímero com cavidades seletivas para a Furazolidona. Este polímero foi, misturado com grafite e perafina de modo a produzir uma pasta de carbono. Uma seringa de plástico foi usada como suporte da pasta de carbono. O comportamento eletroquímico do sensor foi avaliado e diversas condições de utilização foram estudadas e otimizadas. O sensor apresenta um comportamento linear entre a intensidade do pico e a concentração numa gama de concentrações entre 1 e 100 μM, um limite de deteção de 1 μM e uma precisão (repetibilidade) inferior a 7%. A aplicabilidade do sensor fabricado em amostras complexas foi avaliada pela deteção do fármaco em amostras de urina.

Effects of Environmental Organochlorine Pesticides on Human Breast Cancer: Putative Involvement on Invasive Cell Ability

Human exposure to persistent organic pollutants (POPs) is a certainty, even to long banned pesticides like o,p′-dichlorodiphenyltrichloroethane (o,p′-DDT), and its metabolites p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), and p,p′-dichlorodiphenyldichloroethane (p,p′-DDD). POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p′-DDT, p,p′-DDE, and p,p′-DDD (50–1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology.

Assessment of non-steroidal anti-inflammatory and analgesic pharmaceuticals in seawaters of North of Portugal: Occurrence and environmental risk

The occurrence of seven pharmaceuticals and two metabolites belonging to non-steroidal anti-inflammatory drugs and analgesics therapeutic classes was studied in seawaters. A total of 101 samples covering fourteen beaches and five cities were evaluated in order to assess the spatial distribution of pharmaceuticals among north Portuguese coast. Seawaters were selected in order to embrace different bathing water quality (excellent, good and sufficient). Acetaminophen, ketoprofen and the metabolite hydroxyibuprofen were detected in all the seawater samples at maximum concentrations of 584, 89.7 and 287 ng L− 1, respectively. Carboxyibuprofen had the highest seawater concentration (1227 ng L− 1). The temporal distribution of the selected pharmaceuticals during the bathing season showed that, in general, higher concentrations were detected in August and September. The environmental risk posed by the pharmaceuticals detected in seawaters towards different trophic levels (fish, daphnids and algae) was also assessed. Only diclofenac showed hazard quotients above one for fish, representing a potential risk for aquatic organisms. These results were observed in seawaters classified as excellent bathing water. Additional data is needed in order to support the identification and prioritization of risks posed by pharmaceuticals in marine environment.

Development of a SPE–UHPLC–MS/MS methodology for thedetermination of non-steroidal anti-inflammatory and analgesicpharmaceuticals in seawaterPaula

An analytical methodology for the simultaneous determination of seven pharmaceuticals and two metabolites belonging to the non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics therapeutic groups was developed based on off-line solid-phase extraction and ultra-high performance liquid chromatography coupled to tandem mass spectrometry (SPE–UHPLC–MS/MS). Extraction conditions were optimized taking into account parameters like sorbent material, sample volume and sample pH. Method detection limits (MDLs) ranging from 0.02 to 8.18 ng/L were obtained. This methodology was successfully applied to the determination of the selected pharmaceuticals in seawater samples of Atlantic Ocean in the Northern Portuguese coast. All the pharmaceuticals have been detected in the seawater samples, with pharmaceuticals like ibuprofen, acetaminophen, ketoprofen and the metabolite hydroxyibuprofen being the most frequently detected at concentrations that can reach some hundreds of ng/L.