N6-methoxy-2-alkynyladenosine derivatives as highly potent and selective ligands at the human A3 adenosine receptor

A new series of N6-methoxy-2-(ar)alkynyladenosine derivatives has been synthesized and tested at the human recombinant adenosine receptors. Binding studies demonstrated that the new compounds possess high affinity and selectivity for the A3 subtype. Among them, compounds bearing an N-methylcarboxamido substituent in the 4'-position showed the highest A3 affinity and selectivity. In particular, the N6-methoxy-2-p-acetylphenylethynylMECA (40; Ki A3 = 2.5 nM, A3 selectivity versus A1 = 21 500 and A2A = 4200) results in one of the most potent and selective agonists at the human A3 adenosine receptor reported so far. Furthermore, functional assay, performed with selected new compounds, revealed that the presence of an alkylcarboxamido group in the 4'-position seems to be essential to obtain full agonists at the A3 subtype. Finally, results of molecular docking analysis were in agreement with binding and functional data and could explain the high affinity and potency of the new compounds.     

Emotional eating in anorexia nervosa and bulimia nervosa

ObjectivesThe relationship between emotional states and eating behaviors is complex, and emotional eating has been identified as a possible factor triggering binge eating in bulimia nervosa (BN) and binge eating disorder. Few studies considered emotional eating in patients with anorexia nervosa.MethodsThe present study evaluated the clinical correlates of emotional eating in 251 eating-disordered (EDs) subjects (70 AN restricting type, 71 AN binge eating/purging type, 110 BN purging type) and in a group of 89 healthy control subjects. Subjects were assessed by means of a clinical interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and several self-reported questionnaires, including the Emotional Eating Scale (EES).ResultsNo significant differences were found between the 3 EDs groups in terms of EES total score, and all patients with ED showed higher EES scores compared with control subjects. Emotional eating was associated with subjective binge eating in AN binge eating/purging type and with objective binge eating in patients with BN. Among patients with AN restricting type, emotional eating was associated with restraint, but this association was lost when controlling for fear of loss of control over eating, which was the principal determinant of restraint.ConclusionEmotional eating and fear of loss of control over eating are significantly associated with specific eating attitudes and behaviors, according to the different diagnoses. Emotional eating is a relevant psychopathologic dimension that deserves a careful investigation in both anorectic and bulimic patients.     

Age-related influence on thiol, disulfide, and protein-mixed disulfide levels in human plasma

In this study, plasma levels of both low-molecular-mass sulfhydryls/disulfides and mixed disulfides with proteins in 41 healthy humans aged 21-92 years were measured, with the aim of assessing whether there is a shift of the thiol/disulfide balance during aging and verifying some of the possible effects of the thiol imbalance. Our data suggest that aging is strictly correlated to a decrease in plasma glutathione and cysteinylglycine with the concomitant increase of most oxidized forms of thiols and a parallel increase in total cysteine and total homocysteine, probably due to an augmented efflux of these amino acids from various organs. The occurrence of two distinct regulatory systems for plasmatic pools of glutathione/cysteinylglycine on the one hand and cysteine/homocysteine on the other hand is hypothesized.     

Virtual planning for autonomous inspection of electromechanical products

High quality electromechanical products require sophisticated and costly diagnostic tools to ensure the absence of defects in the final artefacts. The main requirements for reliability tests are flexibility, sensor sharing and early defect detection. The aim is the substitution of the current practice based on manual checking of few samples with standardized and repeatable quality control carried out by autonomous mobile platforms. Virtual planning of the inspection tasks, the simulation of the navigation in a poorly structured environment as well as the interaction with the product, are crucial aspects which have been faced through a dedicated system framework. The paper proposes a solution composed of a software for the virtual planning and simulation of inspection tasks, hardware setup composed of an autonomous platform with sensors and actuators, and a service oriented software infrastructure for navigation and perception. Consistent paths to be followed by the robot are elaborated in a graphical environment on the basis of inspected product locations and measuring tasks. The system has been implemented for household appliance inspection in reliability laboratories where life tests are carried out under real operation conditions. The results in terms of inspection mission planning capabilities and localization performances are presented.     

Effects of MMP inhibitors incorporated within dental adhesives

Matrix metalloproteinase (MMP) inhibition has been shown to reduce adhesive bond degradation when applied as a pre-conditioner, adding to clinical steps in the placement of adhesives, but their incorporation within dental adhesives has not been fully explored. This study examined the effect of including 2 MMP inhibitors (BB94 and GM6001) within the primers of 3 commercially available adhesives. Fluorometric assay and zymography showed that adhesives with MMP inhibitors had high affinity toward both synthetic fluorogenic FRET peptides (95%) and dentin powder substrates, respectively. The immediate microtensile bond strength was enhanced for 2 types of adhesives following the addition of both inhibitors. However, no changes were detected between the control and the inhibitor groups following 3-month storage. The modified two-step etch-and-rinse and single-step systems showed less Rhodamine B penetration to the "hybrid layer" and to the "adhesive", respectively. The incorporation of BB94 and GM6001 within the primers resulted in the inhibition of dentin MMPs with improved initial bond strength and enhanced sealing ability.     

Effects of different photo-polymerization protocols on resin-dentine μTBS, mechanical properties and cross-link density of a nano-filled resin composite

Objectives

To evaluate the effects of four different light-curing protocols on the microtensile bond strength (μTBS), ultimate tensile strength (UTS), Knoop micro-hardness (KH) and cross-link density (CLD) of a nano-filled resin composite.

Methods

Filtek Supreme XT (3M-ESPE) was used for the entire experiments following four light-curing approaches: ST, standard irradiance; HI, high irradiance; PD, pulse delay; SS, soft start. The specimens were submitted to different storage periods (24 h or 6 months), cut into match-sticks and subsequently submitted to μTBS testing. Hourglass specimens were also prepared for UTS and KH. Cylindrical specimens were prepared for the CLD evaluation after absolute ethanol challenge. The results were statistically analyzed with a two-way ANOVA and Tukey's test (α = 0.05).

Results

For UTS and KH, continuous irradiance (PD and SS) induced statistically higher results (p < 0.05) both after 24 h and 6 months of water storage compared to ST and HI groups. However, a drop in UTS and KH was obtained after 6 months in all groups. The μTBS was not affected by the different light-curing approaches and, no statistical differences (p > 0.05) were observed between 24 h and 6 months storage. The CLD evaluation showed a statistical drop in KH after 24 h of ethanol storage for PD and SS (step-curing protocols) compared to those attained in continuous mode (ST and HI).

Conclusion

The soft-start mode may improve the UTS and KH of nano-filled resin composites without compromising the resin–dentine μTBS. However, both the step-curing protocols may reduce the cross-link density of the composite polymeric network.

Clinical significance

High irradiances photo-polymerization may be adequate for direct aesthetic restorations such as veneers and onlays. Meanwhile, the soft start protocol would seem more appropriate for the photo-polymerization of high c-factors class I and II restorations.