Transport of small anionic and neutral solutes through chitosan membranes: Dependence on cross-linking and chelation of divalent cations

Chitosan membranes were prepared by solvent casting and cross-linked with glutaraldehyde at several ratios under homogeneous conditions. The cross-linking degree, varying from 0 to 20%, is defined as the ratio between the total aldehyde groups and the amine groups of chitosan. Permeability experiments were conducted using a side-by-side diffusion cell to determine the flux of small molecules of similar size but with different chemical moieties, either ionized (benzoic acid, salicylic acid, and phthalic acid) or neutral (2-phenylethanol) at physiological pH. The permeability of the different model molecules revealed to be dependent on the affinity of those structurally similar molecules to chitosan. The permeability of the salicylate anion was significantly enhanced by the presence of metal cations commonly present in biological fluids, such as calcium and magnesium, but remained unchanged for the neutral 2-phenylethanol. This effect could be explained by the chelation of metal cations on the amine groups of chitosan, which increased the partition coefficient. The cross-linking degree was also correlated with the permeability and partition coefficient. The change in the permeation properties of chitosan to anionic solutes in the presence of these metallic cations is an important result and should be taken into consideration when trying to make in vitro predictions of the drug release from chitosan-based controlled release systems

The impact of polyphenols on chondrocyte growth and survival: a preliminary report

Background: Imbalances in the functional binding of fibroblast growth factors (FGFs) to their receptors (FGFRs) have consequences for cell proliferation and differentiation that in chondrocytes may lead to degraded cartilage. The toxic, proinflammatory, and oxidative response of cytokines and FGFs can be mitigated by dietary polyphenols. Objective: We explored the possible effects of polyphenols in the management of osteoarticular diseases using a model based on the transduction of a mutated human FGFR3 (G380R) in murine chondrocytes. This mutation is present in most cases of skeletal dysplasia and is responsible for the overexpression of FGFR3 that, in the presence of its ligand, FGF9, results in toxic effects leading to altered cellular growth. Design: Different combinations of dietary polyphenols derived from plant extracts were assayed in FGFR3 (G380R) mutated murine chondrocytes, exploring cell survival, chloride efflux, extracellular matrix (ECM) generation, and grade of activation of mitogen-activated protein kinases. Results: Bioactive compounds from Hibiscus sabdariffa reversed the toxic effects of FGF9 and restored normal growth, suggesting a probable translation to clinical requests in humans. Indeed, these compounds activated the intracellular chloride efflux, increased ECM generation, and stimulated cell proliferation. The inhibition of mitogen-activated protein kinase phosphorylation was interpreted as the main mechanism governing these beneficial effects. Conclusions: These findings support the rationale behind the encouragement of the development of drugs that repress the overexpression of FGFRs and suggest the dietary incorporation of supplementary nutrients in the management of degraded cartilage.The authors are grateful for the constant support provided by the Hospital Universitari de Sant Joan and the Universitat Rovira i Virgili. Salvador Fernández-Arroyo is the recipient of a Sara Borrell grant (CD12/00672) from the Instituto de Salud Carlos III, Madrid, Spain. The authors also thank the Andalusian Regional Government Council of Innovation and Science for the Excellence Project P11-CTS-7625 and Generalitat Valenciana for the project PROMETEO/2012/007. This work was also supported by projects of the Fundación Areces and the Fundación MAGAR

Kinematics and Age of Syn-Intrusive Detachment Faulting in the Southern Alps: Evidence for Early Permian Crustal Extension and Implications for the Pangea A Versus B Controversy

Permian basin formation and magmatism in the Southern Alps of Italy have been interpreted as expressions of a WSW‐ENE‐trending, dextral megashear zone transforming Early Permian Pangea B into Late Permian Pangea A between ~285 and 265 Ma. In an alternative model, basin formation and magmatism resulted from N‐S crustal extension. To characterize Permian tectonics, we studied the Grassi Detachment Fault, a low‐angle extensional fault in the central Southern Alps. The footwall forms a metamorphic core complex affected by upward‐increasing, top‐to‐the‐southeast mylonitization. Two granitoid intrusions occur in the core complex, the synmylonitic Val Biandino Quartz Diorite and the postmylonitic Valle San Biagio Granite. U‐Pb zircon dating yielded crystallization ages of 289.1 ± 4.5 Ma for the former and 286.8 ± 4.9 Ma for the latter. Consequently, detachment‐related mylonitic shearing took place during the Early Permian and ended at ~288 Ma, but kinematically coherent brittle faulting continued. Considering 30° anticlockwise rotation of the Southern Alps since Early Permian, the extension direction of the Grassi Detachment Fault was originally ~N‐S. Even though a dextral continental wrench system has long been regarded as a viable model at regional scale, the local kinematic evidence is inconsistent with this and, rather, supports N‐S extensional tectonics. Based on a compilation of >200 U‐Pb zircon ages, we discuss the evolution and tectonic framework of Late Carboniferous to Permian magmatism in the Alps

Modelling residuals dependence in dynamic life tables: A geostatistical approach

The problem of modelling dynamic mortality tables is considered. In this context, the influence of age on data graduation needs to be properly assessed through a dynamic model, as mortality progresses over the years. After detrending the raw data, the residuals dependence structure is analysed, by considering them as a realisation of a homogeneous Gaussian random field defined on . This setting allows for the implementation of geostatistical techniques for the estimation of the dependence and further interpolation in the domain of interest. In particular, a complex form of interaction between age and time is considered, by taking into account a zonally anisotropic component embedded into a nonseparable covariance structure. The estimated structure is then used for prediction of mortality rates, and goodness-of-fit testing is performed through some cross-validation techniques. Comments on validity and interpretation of the results are given.