N-(Anilinoethyl)amide Melatonergic Ligands with Improved Water Solubility and Metabolic Stability

The MT₂-selective melatonin receptor ligand UCM765 (N-(2-((3-methoxyphenyl)(phenyl)amino)ethyl)acetamide), showed interesting sleep inducing, analgesic and anxiolytic properties in rodents, but suffers from low water solubility and modest metabolic stability. To overcome these limitations, different strategies were investigated, including modification of metabolically liable sites, introduction of hydrophilic substituents and design of more basic derivatives. Thermodynamic solubility, microsomal stability and lipophilicity of new compounds were experimentally evaluated, together with their MT₁ and MT₂ binding affinities. Introduction of a m-hydroxymethyl substituent on the phenyl ring of UCM765 and replacement of the replacement of the N,N-diphenyl-amino scaffold with a N-methyl-N-phenyl-amino one led to highly soluble compounds with good microsomal stability and receptor binding affinity. Docking studies into the receptor crystal structure provided a rationale for their binding affinity. Pharmacokinetic characterization in rats highlighted higher plasma concentrations for the N-methyl-N-phenyl-amino derivative, consistent with its improved microsomal stability and makes this compound worthy of consideration for further pharmacological investigation.     

Enthalpy- versus Entropy-Driven Molecular Recognition in the Era of Biologics

Our laboratory has recently identified two nanobodies (small antibodies produced by camelids)—Nb1 and Nb6—that bind efficiently to epithelial growth factor (EGF) and inhibit its ability to activate its receptor (EGFR). Because of the relevance of the EGF/EGFR axis as a target in oncology, these new nanobodies have promising therapeutic potential. This article, however, is focused on another feature of these nanobodies: their distinct thermodynamic signatures. Nb1 binds to EGF through an entropy-driven mechanism whereas Nb6 binds to this factor under enthalpic control. We discuss the advantages and disadvantages of each mechanism in the contexts of traditional medical chemistry (small-molecule drugs) and also of biological drugs. In this latter case, the implications in terms of selectivity are far from being clearly established and further experimental data are required. Their monomeric natures, high stability, and ease of recombinant production make nanobodies ideally suited for thermodynamic studies. Moreover, nanobodies, thanks to their simpler structures in comparison with conventional antibodies, might provide better understanding of the structural basis of the thermodynamic parameters of antigen recognition.     

Influence of amalgam fillings on Hg levels and total antioxidant activity in plasma of healthy donors

In order to evaluate the influence of specific factors on mercury (P-Hg) levels and antioxidant power (P-FRAP) in human plasma, 26 healthy donors were examined by a dentist, their plasma analyzed for Hg by atomic absorption spectrometry and for total antioxidant activity by FRAP method. Hg plasma concentration was found to be correlated with the number of amalgam fillings, suggesting that Hg released from fillings is a source of Hg in non-occupational exposed subjects. P-FRAP correlated negatively with P-Hg suggesting a pro-oxidant role of the Hg released from amalgam fillings. Though age by itself was not significantly correlated with P-FRAP, when considered together with P-Hg in multivariate analysis, it was found to be a major related cofactor. Multivariate analysis showed no influence of fish consumption or cigarette smoking on P-FRAP.     

Pectins from Aloe Vera: Extraction and production of gels for regenerative medicine

Extraction, purification, and gel preparation of Aloe Vera pectin and the evaluation of the biocompatibility of the pectin gels were studied, considering as end use as implantable materials for regenerative medicine. A. Vera was chosen as source of pectin, as this pectin was described to possess high molecular weight and a low degree of esterification. As the properties of pectins are strictly dependent upon the extraction methods in combination with the natural source, the extraction method was modified in order to optimize the yield of the final product, its purity, the duration of the process and the selection of non‐toxic chemical reagents. Changing the experimental conditions resulted in four different extraction processes and products with different physical and chemical characteristics. The optimal extraction resulted to be the process: with enzimatic deactivation by microwave and the use of sodium citrate as chelating agent the molecular weight of the pectin extracted was estimated to be 118 kDa and the 2.93% esterification degree. Cytocompatibility of pectin gels, prepared by ionotropic gelation, showing an improved cell adhesion if compared to commercial pectin. The results suggest that the extracted A. Vera pectins possess interesting properties to be exploited for the production of mechanically stable gels by ionotropic gelation and high rhamnose content matrices for application in regenerative medicine. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39760.     

A new spontaneous pupillary oscillation-based verification system

A novel pupillary-based verification system is introduced, along with the early identity authentication results and analysis, based on the spatio-temporal features computed from the spontaneous pupillary oscillations. The authors demonstrate that this biometric trait has the capability to provide enough discriminative information to authenticate the identity of a subject. A new methodology to compute the spatio-temporal biometric template recordings of the pupil area changes, in a video-oculography sequence under constant luminance level, is also introduced in this paper. According to the authors’ knowledge, there is no evidence that other attempts were made, addressing this methodology to distinguish individuals based on the spatio-temporal representations, computed from the normal dilation-contraction behavior of the pupil. In this work, liveness will be detected by using the information obtained from the spontaneous pupillary oscillation mechanism. Preliminary experiments were conducted by using a particular own collected database, resulting in a (Equal Error Rate) in the order of 0.2338%.     

Enzyme activity during germination of different cereals: A review

The germination process increases enzymatic activity. However, this does not occur in the same way in all cereals. It depends on the type of enzyme, the cereal, and the conditions of germination. During germination, most enzymes are localized in the aleurone layer and the scutellum. Some of them, such as xylanases, proteases, and β-glucanases, are also localized in the endosperm while β-glucanases and lipases have been identified in the embryo. The maximum activity of the enzymes in most cereals start from day 4 of germination. Germination allows the hydrolysis of macromolecules and compounds like β-glucans and phytic acid. In cereals, starch is the component that presents the most morphological changes. Germination mobilizes and increases the activity of some enzymes. Temperature, steeping time, and variety are determining factors in the activation time. At higher temperatures, the enzymatic activation is generally faster; however, there are some exceptions. The use of germination could be a promising resource for modifying grain properties and increase enzymatic activity; also, this process is simple and economical.