Magnetic resonance contrast agents from viral capsid shells: a comparison of exterior and interior cargo strategies

Two high-relaxivity nanoscale magnetic resonance contrast agents have been built using bacteriophage MS2 as a biomolecular scaffold. Protein capsid shells were functionalized on either the exterior or interior surface to display multiple copies of an aldehyde functional group. Subsequently, approximately 90 heteropodal bis(hydroxypyridonate)terephthalamide ligands were attached to these sites through oxime condensation reactions. Upon complexation with Gd3+, contrast agents with ionic relaxivities of up to 41.6 mM-1 s-1 (30 MHz, 25 degrees C) and total molecular relaxivities of up to 3900 mM-1 s-1 (30 MHz, 25 degrees C) were produced. Capsids sequestering the Gd-chelates on the interior surface (attached through tyrosine residues) not only provided higher relaxivities than their exterior functionalized counterparts (which relied on lysine modification) but also exhibited improved water solubility and capsid stability. The attachment functional cargo to the interior surface is envisioned to minimize its influences on biodistribution, yielding significant advantages for tissue targeting by additional groups attached to the capsid exterior.     

Solid lipid nanoparticles incorporating melatonin as new model for sustained oral and transdermal delivery systems

melatonin (MT) is a hormone produced by the pineal gland at night, involved in the regulation of circadian rhythms. For clinical purposes, exogenous MT administration should mimic the typical nocturnal endogenous MT levels, but its pharmacokinetics is not favourable due to short half-life of elimination. Aim of this study is to examine pharmacokinetics of MT incorporated in solid lipid nanoparticles (SLN), administered by oral and transdermal route. SLN peculiarity consists in the possibility of acting as a reservoir, permitting a constant and prolonged release of the drugs included. In 7 healthy subjects SLN incorporating MT 3 mg (MT-SLN-O) were orally administered at 8.30 a.m. MT 3 mg in standard formulation (MT-S) was then administered to the same subjects after one week at 8.30 a.m. as controls. In 10 healthy subjects SLN incorporating MT were administered transdermally (MT-SLN-TD) by the application of a patch at 8.30 a.m. for 24 hours. Compared to MT-S, Tmax after MT-SLN-O administration resulted delayed of about 20 minutes, while mean AUC and mean half life of elimination was significantly higher (respectively 169944.7 +/- 64954.4 pg/ml x hour vs. 85148.4 +/- 50642.6 pg/ml x hour, p = 0.018 and 93.1 +/- 37.1 min vs. 48.2 +/- 8.9 min, p = 0.009). MT absorption and elimination after MT-SLN-TD demonstrated to be slow (mean half life of absorption: 5.3 +/- 1.3 hours; mean half life of elimination: 24.6 +/- 12.0 hours), so MT plasma levels above 50 pg/ml were maintained for at least 24 hours. This study demonstrates a significant absorption of MT incorporated in SLN, with detectable plasma level achieved for several hours in particular after transdermal administration. As dosages and concentrations of drugs included in SLN can be varied, different plasma level profile could be obtained, so disclosing new possibilities for sustained delivery systems.     

CO oxidation on Pd/CeO2–ZrO2 catalysts

The promotive effects of cerium oxide on commercial three-way catalysts (TWCs) for purification of motor exhaust gases have been widely investigated in recent years. This work shows the cooperative effects of CeO₂–Pd on the kinetics of CO oxidation over Pd/CeO₂–ZrO₂. Under reducing-to-moderately oxidizing conditions, a zero-order O₂ pressure dependence is found which can be interpreted on the basis of a mechanism involving a reaction between CO adsorbed on Pd and surface oxygen from the support. The high oxygen-exchange capability of the CeO₂–ZrO₂ support, as determined from temperature-programmed reduction/oxygen uptake measurements is suggested as being responsible for such a catalytic behavior.     

Photooxidation in Water by New Hybrid Molecular Photocatalysts Integrating an Organic Sensitizer with a Polyoxometalate Core

Hybrid compounds consisting of an organic sensitizer and a polyoxometalate unit were synthesized following two strategies: a) the covalent functionalization of lacunary decatungstosilicate with organosilylfulleropyrrolidines; b) the charge interaction between cationic sensitizers and the polyoxoanions, yielding electrostatic aggregates. These hybrid complexes effect catalytic photooxygenation in water under heterogeneous conditions, 25 °C and O₂ (1 atm), using visible light irradiation (λ>375 nm). As representative target substrates, phenol (4 mM) is oxidized in 150 min with a COD loss up to 30% (TON up to 50), while L ‐methionine methyl ester (15 mM) undergoes selective photooxygenation to the corresponding sulfoxide in 90 min (TON up to 200). The photocatalyst stability has been evaluated on the basis of system recycling along three oxidation runs. The inhibition exerted by sodium azide, a typical ¹O₂ quencher, suggests the occurrence of a Type II photooxidation mechanism.     

Epigenetic Dysregulations in Merkel Cell Polyomavirus-Driven Merkel Cell Carcinoma

Merkel cell polyomavirus (MCPyV) is a small DNA virus with oncogenic potential. MCPyV is the causative agent of Merkel Cell Carcinoma (MCC), a rare but aggressive tumor of the skin. The role of epigenetic mechanisms, such as histone posttranslational modifications (HPTMs), DNA methylation, and microRNA (miRNA) regulation on MCPyV-driven MCC has recently been highlighted. In this review, we aim to describe and discuss the latest insights into HPTMs, DNA methylation, and miRNA regulation, as well as their regulative factors in the context of MCPyV-driven MCC, to provide an overview of current findings on how MCPyV is involved in the dysregulation of these epigenetic processes. The current state of the art is also described as far as potentially using epigenetic dysregulations and related factors as diagnostic and prognostic tools is concerned, in addition to targets for MCPyV-driven MCC therapy. Growing evidence suggests that the dysregulation of HPTMs, DNA methylation, and miRNA pathways plays a role in MCPyV-driven MCC etiopathogenesis, which, therefore, may potentially be clinically significant for this deadly tumor. A deeper understanding of these mechanisms and related factors may improve diagnosis, prognosis, and therapy for MCPyV-driven MCC.     

Design and development of a pneumatic anthropomorphic hand

This work deals with a pneumatically actuated hand composed of four fingers and an opposable thumb. Mechanisms to convert actuator motion into phalanx rotation were studied to make each finger as similar as possible to the human specimen. Force tactile sensors are disposed along the phalanxes to allow a closed‐loop force control, while the thumb position is sensorized by a potentiometer and hence position controlled. Each component is controlled by fuzzy logic. This solution allowed the existing strong nonlinearities to be easily managed. A fuzzy supervisor applies a grasping strategy whose target is an approximate identification of the shape and size of an object to grasp it most efficiently with the disposable fingers. ©2000 John Wiley & Sons, Inc.     

Using TRIO for designing a CORBA‐based application

We report on our experience in the Esprit OpenDREAMS project that targets the domain of Supervision and Control Systems (SCS). During this project we studied how a CORBA‐based application can be designed starting from a typical SCS requirement document by integrating a formal approach with some CORBA concepts. We present a case study that shows how an existing object‐oriented methodology based on the formal specification language TRIO can be tailored towards supporting CORBA‐based applications. The application taken into account is in the field of the Energy Management Systems, namely a diagnostic system for the steam condenser of a thermoelectric power plant. The paper describes how to obtain the architectural design of a CORBA‐based application starting from the formal specification of its requirements expressed in TRIO by means of a sequence of transformation steps. At the end of such sequence of steps a complete structure of the application classes, with their mutual relations and their IDL interfaces, is built. Finally, the paper discusses how TRIO can be used to validate the architectural choices made with respect to the application critical requirements. Copyright © 2000 John Wiley & Sons, Ltd.     

Equine Chorionic Gonadotropin as an Effective FSH Replacement for In Vitro Ovine Follicle and Oocyte Development

The use of assisted reproductive technologies (ART) still requires strategies through which to maximize individual fertility chances. In vitro folliculogenesis (ivF) may represent a valid option to convey the large source of immature oocytes in ART. Several efforts have been made to set up ivF cultural protocols in medium-sized mammals, starting with the identification of the most suitable gonadotropic stimulus. In this study, Equine Chorionic Gonadotropin (eCG) is proposed as an alternative to Follicle Stimulating Hormone (FSH) based on its long superovulation use, trans-species validation, long half-life, and low costs. The use of 3D ivF on single-ovine preantral (PA) follicles allowed us to compare the hormonal effects and to validate their influence under two different cultural conditions. The use of eCG helped to stimulate the in vitro growth of ovine PA follicles by maximizing its influence under FBS-free medium. Higher performance of follicular growth, antrum formation, steroidogenic activity and gap junction marker expression were recorded. In addition, eCG, promoted a positive effect on the germinal compartment, leading to a higher incidence of meiotic competent oocytes. These findings should help to widen the use of eCG to ivF as a valid and largely available hormonal support enabling a synchronized in vitro follicle and oocyte development.