Ochratoxin A exposure assessment of the inhabitants of Lisbon during winter 2007/2008 through bread and urine analysis

A survey on the occurrence of ochratoxin A (OTA) in 41 bread samples was carried out in the Portuguese capital, Lisbon. Maize (5) and wheat bread (36) and 43 representative urine samples from the Lisbon region were assayed for OTA levels using immunoaffinity column cleanup (IAC) and HPLC with fluorimetric detection (LC–FD). The percentage of OTA-positive samples was slightly higher for maize bread (80%) than wheat bread (70.8%), although, due to its higher consumption, the latter contributes more to OTA exposure, featuring a higher estimated daily intake (EDI). In the urine samples analyzed, both female and male residents displayed similarly high levels of OTA frequency and average contamination. In summary, OTA is a food contaminant of concern and may constitute a hazard for public health through consumption of cereal-based products.     

Fullerene C₆₀ as a multifunctional system for drug and gene delivery

The fullerene family, and especially C(60), has delighted the scientific community during the last 25 years with perspective applications in a wide variety of fields, including the biological and the biomedical domains. Several biomedical uses have been explored using water-soluble C(60)-derivatives. However, the employment of fullerenes for drug delivery is still at an early stage of development. The design and synthesis of multifunctionalized and multimodal C(60) systems able to cross the cell membranes and efficiently deliver active molecules is an attracting challenge that involves multidisciplinary strategies. Promising results have emerged in the last years, bringing fullerenes again to the front of interest. Herein, the state of the art of this emerging field is presented and illustrated with some of the most representative examples.     

Notch Signaling Regulation in Autoinflammatory Diseases

Notch pathway is a highly conserved intracellular signaling route that modulates a vast variety of cellular processes including proliferation, differentiation, migration, cell fate and death. Recently, the presence of a strict crosstalk between Notch signaling and inflammation has been described, although the precise molecular mechanisms underlying this interplay have not yet been fully unravelled. Disruptions in Notch cascade, due both to direct mutations and/or to an altered regulation in the core components of Notch signaling, might lead to hypo- or hyperactivation of Notch target genes and signaling molecules, ultimately contributing to the onset of autoinflammatory diseases. To date, alterations in Notch signaling have been reported as associated with three autoinflammatory disorders, therefore, suggesting a possible role of Notch in the pathogenesis of the following diseases: hidradenitis suppurativa (HS), Behçet disease (BD), and giant cell arteritis (GCA). In this review, we aim at better characterizing the interplay between Notch and autoinflammatory diseases, trying to identify the role of this signaling route in the context of these disorders.     

Robust estimators under semi‐parametric partly linear autoregression: Asymptotic behaviour and bandwidth selection

Abstract. In this article, under a semi‐parametric partly linear autoregression model, a family of robust estimators for the autoregression parameter and the autoregression function is studied. The proposed estimators are based on a three‐step procedure, in which robust regression estimators and robust smoothing techniques are combined. Asymptotic results on the autoregression estimators are derived. Besides combining robust procedures with M‐smoothers, predicted values for the series and detection residuals, which allow to detect anomalous data, are introduced. Robust cross‐validation methods to select the smoothing parameter are presented as an alternative to the classical ones, which are sensitive to outlying observations. A Monte Carlo study is conducted to compare the performance of the proposed criteria. Finally, the asymptotic distribution of the autoregression parameter estimator is stated uniformly over the smoothing parameter.     

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD⁺-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems.     

Synthesis and characterization of new injectable and degradable dextran-based hydrogels

Injectable and degradable hydrogels are very interesting networks for drug delivery and cell transplantation applications since they can be administered in the human body in a minimally invasive way. In most cases, the crosslinking reaction occurs by photopolymerisation or free radical polymerisation; however, the use of chemical initiators may promote cell death. In the current work, injectable and degradable dextran-based hydrogels were prepared without the use of initiators. Dextran, a natural glucose-containing polysaccharide, was oxidized with sodium periodate (dexOx) and the derivatives characterized by NMR and FTIR spectroscopy's as well as by colorimetric techniques. The oxidized derivatives were crosslinked with adipic acid dihydrazide (AAD), forming a gel within 2-4 min. The obtained hydrogels were characterized by their mechanical properties, swelling and degradation behavior under physiologic conditions. In addition, the hydrogel interior morphology as well as porous structure was evaluated by scanning electron microscopy (SEM) and mercury intrusion porosimetry (MIP). MIP analysis showed that dexOx hydrogels crosslinked with 10% of AAD were macroporous with pore sizes ranging from 0.32 to 0.08 μm. As expected, the average pore size increased during hydrogel degradation as confirmed by SEM and MIP studies.     

Small‐angle X‐ray scattering study of modified porous suspension–poly(vinyl chloride) particles

Small‐angle X‐ray scattering (SAXS) was applied to investigate the microstructure of unmodified and modified porous commercial suspension‐type poly(vinyl chloride) (PVC) particles. The modified PVC particles were prepared by an in situ stabilizer‐free polymerization/crosslinking of particles absorbed with a monomer/crosslinker/peroxide solution. The modifying polymers include styrene with or without divinyl benzene (DVB) as a crosslinker and methyl methacrylate (MMA) with or without ethylene glycol dimethacrylate (EGDMA) as a crosslinker. The SAXS method was used to highlight the effect of polystyrene (PS) on the microstructure of PVC particles and to evaluate the characteristic lengths, both in the PVC/PS and the PVC/XPS (PS crosslinked with 0 and 5% DVB, respectively) systems. A model is suggested, where during the synthesis modification process, swelling of PVC by styrene and styrene polymerization occur simultaneously. PVC swelling by styrene causes destruction of the PVC subprimary particles, whereas styrene polymerization leads to phase separation resulting from incompatibility of the polymers. It was further suggested that because of PVC swelling by styrene, structure of the subprimary particles is lost. Therefore the characteristic lengths of PVC/PS and PVC/XPS, as calculated from the SAXS measurements, were attributed to the size of the phase‐separated PS and XPS inclusions, respectively. The SAXS method also shows that PMMA and XPMMA do not influence the PVC microstructure. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 95: 1024–1031, 2005     

Catalyst pore plugging effects on hydrocracking reactions in an Ebullated bed reactor operation

This paper analyzes the deactivation effects of NiMo/Al₂O₃ catalyst during the operation in an Ebullated bed reactor for Heavy residue hydrocracking. The spent catalysts were characterized by chemical analysis, ¹³C NMR, ESM, DRX, and by using thermal programmed oxidation and diffusion studies in a shallow bed micro-reactor. The deactivations were performed in a 5 l continuously stirred tank reactor, while the spent catalysts were tested in a 0.05 l micro-reactor. The study focused on determining the properties of the external layer of the catalyst and on evaluating the internal coke and metal deposition. The results indicated that initial deactivation is mainly due to coke depositions, while its impact on mass transfer reaction control depends on temperature. In long-term deactivation, the metal deposition plays a more important role in blocking the internal micro- and meso-structures and in building up the external layer of the pellets.     

A potent integrin antagonist from a small library of cyclic RGD pentapeptide mimics including benzyl-substituted azabicycloalkane amino acids

A small library of cyclic RGD pentapeptide mimics, including benzyl-substituted azabicycloalkane amino acids, was synthesized with the aim of developing active and selective integrin antagonists. In vitro binding assays established one particular compound with affinity for both the alpha(v)beta(3) and the alpha(v)beta(5) integrins. The synthesis in solution and the in vitro screening of these RGD derivatives, as well as the determination of the conformational properties of the integrin ligands by spectroscopic and computational methods are described.