Publications

Abstract Purpose: There is nowadays extensive experimental and computational investigation on the pathophysiology of atherosclerosis, searching correlations between its focal nature and local hemodynamic environment. The goal of this work is to present a methodology for patient-specific hemodynamics study of the carotid artery bifurcation based on the use of ultrasound (US) morphological and blood flow velocity patient data. Materials/methods: Subject-specific studies were performed for two patients, using a developed finite element code. Geometrical models were obtained from the acquisition of longitudinal and sequential cross-sectional ultrasound images and boundary conditions from Doppler velocity measurements at the common carotid artery. Results: There was a good agreement between ultrasound imaging data and computational simulated results. For a normal and a stenosed carotid bifurcation the velocity, wall shear stress (WSS) and WSS descriptors analysis illustrated the extremely complex hemodynamic behavior along the cardiac cycle. Different patterns were found, associated with morphology and hemodynamic patient-specific conditions. High values of time-averaged WSS (TAWSS) were found at stenosis site and for both patients TAWSS fields presented low values within areas of high oscillating shear index and relative residence time values, corresponding to recirculation zones. Conclusion: Simulated hemodynamic parameters were able to capture the disturbed flow conditions in a normal and a stenosed carotid artery bifurcation, which play an important role in the development of local atherosclerotic plaques. Computational simulations based on clinic US might help improving diagnostic and treatment management of carotid atherosclerosis.

Abstract A strategy based on water-in-oil emulsion for the dispersion of a sol-gel mixture into small droplets was employed with the view of the production of naproxen-imprinted micro- and nanospheres. The procedure, aiming at a surface imprinting process, comprised the synthesis of a naproxen-derived surfactant. The imprinting process occurred at the interface of the emulsions or microemulsions, by the migration of the NAP-surfactant head into the sol-gel drops to leave surficial imprints due mainly to ion-pair interaction with a cationic group contained within the growing sol-gel network. The surface imprinted microspheric particles exhibited a log-normal size distribution with geometric mean diameter of 3.1 mu m. Amesoporous texture was found from measurements of the specific surface area (206 m(2)/g) and pore diameter (D-P 2 nm). Evaluation of the microspheres as packed HPLC stationary phases resulted in the determination of the selectivity factor against ibuprofen (alpha=2.1), demonstrating the successful imprinting. Chromatographic efficiency, evaluated by the number of theoretical plates (222 plates cm(-3)), emerged as an outstanding feature among the set of all relatable formats produced before, an advantage intrinsic to the location of the imprinted sites on the surface. The material presented a capacity of 3.2 mu mol g(-1). Additionally, exploratory work conducted on their nanoscale counterparts resulted in the production of nanospheres in the size order of 10 nm providing good indications of a successful imprinting process.

Abstract Electrified double-layer (EDL) of ionic liquids electrode interfaces have been attracting considerable interest both from the fundamental and applied points of view. So far from the large set of ionic liquids synthetized only a very limited number has been electrochemically studied. As a consequence, the effect of complex shape and chemical properties of the ions and surface morphology on the structure and mechanism of formation of EDL is far from being understood. Binary mixtures of ionic liquids with a common cation (1-ethyl-3-methylimidazolium) paired with two different anions (bis(trifuoromethylsulfonyl) imide, [Tf N-2](-) and tris(pentafluoroethyl)trifluorophosphate, [FAP](-)) were prepared and their molecular mixing behavior was followed through the changes in their vibrational structure by Fourier transform infrared (ATR-FT-IR) spectroscopy. The interface at Hg and each of the binary mixture was followed by electrochemical impedance spectroscopy and drop time measurements. Differential capacitance and charge-potential curves were obtained and compared with those corresponding to the pure liquids. The data is interpreted as suggesting the coexistence at the interface of a mixture of two limiting structures each of which containing essentially one of the anions and sharing the common cation in a co-network.

Abstract This work describes the state of the art of electrochemical devices for the detection of an important class of neurotransmitters: the catecholamines. This class of biogenic amines includes dopamine, noradrenaline (also called norepinephrine) and adrenaline (also called epinephrine). Researchers have focused on the role of catecholamine molecules within the human body because they are involved in many important biological functions and are commonly associated with several diseases, such as Alzheimer's and Parkinson. Furthermore, the release of catecholamines as a consequence of induced stimulus is an important indicator of reward-related behaviors, such as food, drink, sex and drug addiction. Thus, the development of simple, fast and sensitive electroanalytical methodologies for the determination of catecholamines is currently needed in clinical and biomedical fields, as they have the potential to serve as clinically relevant biomarkers for specific disease states or to monitor treatment efficacy. Currently, three main strategies have used by researchers to detect catecholamine molecules, namely: the use electrochemical materials in combination with, for example, HPLC or FIA, the incorporation of new materials/layers on the sensor surfaces (Tables 1-7) and in vivo detection, manly by using FSCV at CFMEs (Section 10). The developed methodologies were able not only to accurately detect catecholamines at relevant concentration levels, but to do so in the presence of co-existing interferences in samples detected (ascorbate, for example). This review examines the progress made in electrochemical sensors for the selective detection of catecholamines in the last 15 years, with special focus on highly innovative features introduced by nanotechnology. As the literature in rather extensive, we try to simplify this work by summarizing and grouping electrochemical sensors according to the manner their substrates were chemically modified. We also discuss the current and future of electrochemical sensors for catecholamines in terms of the analytical performance of the devices and emerging applications.

Abstract One of the earliest synthetic antimalarial drugs, quinacrine, was recently reported as interesting for the treatment of acute myeloid leukemia. Inspired by this and similar findings, we evaluated a set of quinacrine analogues against gastric (MKN28), colon (Caco-2), and breast (MFC-7) cancer cell lines and one normal human fibroblast cell line (HFF-1). All the compounds, previously developed by us as dual-stage antimalarial leads, displayed antiproliferative activity, and one of the set stood out as selective toward the gastric cancer cell line, MKN-28. Interestingly, this compound was transported across an in vitro MKN-28 model cell line in low amounts, and approximately 80% was trapped inside those cells. Nuclear targeting of the same compound and its interactions with calf thymus DNA were assessed through combined fluorescence microscopy, spectroscopy, and calorimetry studies, which provided evidence for the compound's ability to reach the nucleus and to interact with DNA.

Abstract An immobilization scheme, via glycidyloxypropyl-trimethoxysilane sol-gel crosslinking, of chondroitin sulfate (CS) or fucoidan (Fd), inspired by the biological silicate bridge found in CS, is presented here. It revealed to constitute a simple and effective way of producing biopolymer-silicate composites without compromising the carboxylate- and sulfate- groups of the biopolymers, those which play a determinant role in the binding to metal cations. In the case of the Fd composite, the immobilization process resulted in the similar to 4-fold enhancement of the negatively charged sorption sites, probably due to unfolding effects induced by the synthesis conditions. Textural analysis of the composites showed a microporous, low surface area (6-12 m(2)/g), microstructure which did not prevent the observation of relevant sorption features for metal cations, especially for Pb(II) and Cd(II). Rate constants (1-14 g/mg min(-1)) and affinity constants (79-370L/mg) in the same order of magnitude of chitosan-based sorbents were determined, whereas capacities (2-24 mg/g) were smaller than the generality of those same sorbents. Globally, the sorption of metal cations by the Fd composite was superior to that by the CS composite. Furthermore, high stability of the sorbents and acceptable reproducibility of the synthesis was observed. Overall, the developed scheme of immobilization of CS and Fd appears capable of providing an effective way for integrating these biopolymers into metal cation-related applications such as biosorption, sensing or separation.

Abstract This work reports experimental vapour pressures at different temperatures of four halogenated acetophenones. The liquid phase vapour pressures of p-fluoro and p-chloro acetophenones were measured, respectively, across the temperatures ranges (255.1 to 310.2) K and (271.6 to 335.0) K, using a static method based on capacitance diaphragm manometers. This experimental technique was also used to measure the vapour pressures of both (crystalline and liquid) condensed phases of p-bromo-and p-iodoacetophenones, respectively, through the temperature intervals (295.3 to 378.4) K and (313.1 to 402.0) K. The temperatures and molar enthalpies and entropies of fusion of the four p-halogenated acetophenones were determined using differential scanning calorimetry. The standard molar enthalpies, entropies and Gibbs energies of sublimation and of vaporisation, at selected reference temperatures, were derived from the experimental results. The contributions of the acetyl group and of the constituent halogen atoms to these thermodynamic properties were also predicted through correlation equations.

Abstract Computational methods for Target Fishing (TF), also known as Target Prediction or Polypharmacology Prediction, can be used to discover new targets for small-molecule drugs. This may result in repositioning the drug in a new indication or improving our current understanding of its efficacy and side effects. While there is a substantial body of research on TF methods, there is still a need to improve their validation, which is often limited to a small part of the available targets and not easily interpretable by the user. Here we discuss how target-centric TF methods are inherently limited by the number of targets that can possibly predict (this number is by construction much larger in ligand-centric techniques). We also propose a new benchmark to validate TF methods, which is particularly suited to analyse how predictive performance varies with the query molecule. On average over approved drugs, we estimate that only five predicted targets will have to be tested to find two true targets with submicromolar potency (a strong variability in performance is however observed). In addition, we find that an approved drug has currently an average of eight known targets, which reinforces the notion that polypharmacology is a common and strong event. Furthermore, with the assistance of a control group of randomly-selected molecules, we show that the targets of approved drugs are generally harder to predict. © 2016 Peón, Dang and Ballester.

Abstract A sensitive electrochemical sensor was successfully developed based on a glassy carbon (GC) electrode modified by a combination of multi-walled carbon nanotubes (MWCNT) with beta-cyclodextrin (beta-CD) incorporated in a polyaniline film, and applied to detect and determine the fungicide pyrimethanil in pome fruit (apples). The beta-CD/MWCNT modified GC electrode displayed a detection limit of 1.04 mu M (0.21 mg/kg) which is below the maximum residue levels set for pyrimethanil in pome fruit and citrus fruit by EU regulations. The results indicate that the (beta-CD/MWCNT modified GC electrode exhibits efficient electrocatalytic oxidation of pyrimethanil with high reproducibility, repeatability and stability. Furthermore, the obtained results were in excellent agreement with those obtained using an established HPLC procedure.