Dynamics of model polycyclic aromatic hydrocarbon compound-epoxy composites: A dielectric study

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Rui Ding, Sabrina W. Torres, Jamie Messman, Daniel E. Bowen, Nicola Bowler
A model polycyclic aromatic hydrocarbon (PAH) compound, anthracene, was incorporated into a thermosetting epoxy matrix as a reinforcing moiety via physical dispersion and/or chemical modification. In order to understand the "additive effect" of glass transition temperature (Tg) observed with the variation of free anthracene (AN) and bonded 2-aminoanthracene (2-AM) loading, the relaxation dynamics were investigated by broadband dielectric spectroscopy. Within the measurement range of 0.01 Hz–1 MHz and −60 to 130 °C, three relaxation processes, namely normal mode (n-mode) relaxation, α relaxation, and β relaxation, were observed for all epoxy composites with bonded and/or unbound anthracene. After eliminating the strong effect of ionic conduction by using the logarithmic derivative approximation ε''∝∂ε'∂lnω, derived from the Kramers-Kronig relations, the n-mode relaxation occurring at low frequencies above Tg for the rigid epoxy system is revealed. The Arrhenius diagram showing the temperature dependence of each relaxation process for the PAH-epoxy composites was obtained after parametric fitting using the Havriliak-Negami (HN) function in the frequency domain. The segmental α relaxation was more strongly impacted than the long-range n-mode relaxation by the different reinforcing approaches. The correlation of Tg -scaled fragility to molecular structures reveals the different mechanisms for the retardation effects on cooperative segmental and chain relaxation time. The localized β relaxation below Tg was not seemingly affected by the incorporation of bound and/or unbound anthracenes as indicated by the characteristic relaxation time and the activation energy.

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Microfluidics for producing poly (lactic-co-glycolic acid)-based pharmaceutical nanoparticles

Publication date: Available online 24 December 2017
Source:Advanced Drug Delivery Reviews
Author(s): Xuanyu Li, Xingyu Jiang
Microfluidic chips allow the rapid production of a library of nanoparticles (NPs) with distinct properties by changing the precursors and the flow rates, significantly decreasing the time for screening optimal formulation as carriers for drug delivery compared to conventional methods. The batch-to-batch reproducibility which is essential for clinical translation is achieved by precisely controlling the precursors and the flow rate, regardless of operators. Poly (lactic-co-glycolic acid) (PLGA) is the most widely used Food and Drug Administration (FDA)-approved biodegradable polymers. Researchers often combine PLGA with lipids or amphiphilic molecules to assemble into a core/shell structure to exploit the potential of PLGA-based NPs as powerful carriers for cancer-related drug delivery. In this review, we discuss the advantages associated with microfluidic chips for producing PLGA-based functional nanocomplexes for drug delivery. These laboratory-based methods can readily scale up to provide sufficient amount of PLGA-based NPs in microfluidic chips for clinical studies and industrial-scale production.

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Rescue plan for Achilles: Therapeutics steering the fate and functions of stem cells in tendon wound healing

Publication date: Available online 24 December 2017
Source:Advanced Drug Delivery Reviews
Author(s): Magdalena Schneider, Peter Angele, Tero A.H. Järvinen, Denitsa Docheva
Due to the increasing age of our society and a rise in engagement of young people in extreme and/or competitive sports, both tendinopathies and tendon ruptures present a clinical and financial challenge. Tendon has limited natural healing capacity and often responds poorly to treatments, hence it requires prolonged rehabilitation in most cases. Till today, none of the therapeutic options has provided successful long-term solutions, meaning that repaired tendons do not recover their complete strength and functionality. Our understanding of tendon biology and healing increases only slowly and the development of new treatment options is insufficient.In this review, following discussion on tendon structure, healing and the clinical relevance of tendon injury, we aim to elucidate the role of stem cells in tendon healing and discuss new possibilities to enhance stem cell treatment of injured tendon. To date, studies mainly apply stem cells, often in combination with scaffolds or growth factors, to surgically created tendon defects. Deeper understanding of how stem cells and vasculature in the healing tendon react to growth factors, common drugs used to treat injured tendons and promising cellular boosters could help to develop new and more efficient ways to manage tendon injuries.

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Abnormal cortical brain integration of somatosensory afferents in ALS

Publication date: Available online 24 December 2017
Source:Clinical Neurophysiology
Author(s): Sina Sangari, Alain Giron, Guillaume Marrelec, Pierre-François Pradat, Véronique Marchand-Pauvert
ObjectivesInfraclinical sensory alterations have been reported at early stages of amyotrophic lateral sclerosis (ALS). While previous studies mainly focused on early somatosensory evoked potentials (SEPs), late SEPs, which reflect on cortical pathways involved in cognitive-motor functions, are relatively underinvestigated. Early and late SEPs were compared to assess their alterations in ALS.MethodsMedian and ulnar nerves were electrically stimulated at the wrist, at 9 times the perceptual threshold, in 21 ALS patients without clinical evidence of sensory deficits, and 21 age- and gender-matched controls. SEPs were recorded at the Erb point using surface electrodes and using a needle inserted in the scalp, in front of the primary somatosensory area (with reference electrode on the ear lobe).ResultsCompared to controls, ALS patients showed comparable peripheral (N9) and early cortical component (N20, P25, N30) reductions, while the late cortical components (N60, P100) were more depressed than the early ones.ConclusionsThe peripheral sensory alteration likely contributed to late SEP depression to a lesser extent than that of early SEPs.SignificanceLate SEPs may provide new insights on abnormal cortical excitability affecting brain areas involved in cognitive-motor functions.



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Editorial Board

Publication date: February 2018
Source:Archives of Oral Biology, Volume 86





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Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains

Publication date: Available online 24 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Anna Maria Monforte, Laura De Luca, Maria Rosa Buemi, Fatima E. Agharbaoui, Christophe Pannecouque, Stefania Ferro
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are recommended components of preferred combination antiretroviral therapies used for the treatment of human immunodeficiency virus (HIV) infection. These regimens are extremely effective in suppressing virus replication. Recently, our research group identified some N1-aryl-2-arylthioacetamido-benzimidazoles as a novel class of NNRTIs. In this research work we report the design, the synthesis and the structure-activity relationship studies of new compounds (20-34) in which some structural modifications have been introduced in order to investigate their effects on reverse trascriptase (RT) inhibition and to better define the features needed to increase the antiviral activity. Most of the new compounds proved to be highly effective in inhibiting both RT enzyme at nanomolar concentrations and HIV-1 replication in MT4 cells with minimal cytotoxicity. Among them, the most promising N1-aryl-2-arylthioacetamido-benzimidazoles and N1-aryl-2-aryloxyacetamido-benzimidazoles were also tested toward a panel of single- and double-mutants strain responsible for resistance to NNRTIs, showing in vitro antiviral activity toward single mutants L100I, K103N, Y181C, Y188L and E138K. The best results were observed for derivatives 29 and 33 active also against the double mutants F227L and V106A.. Computational approaches were applied in order to rationalize the potency of the new synthesized inhibitors.

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Benzimidazole design, synthesis, and docking to build selective carbonic anhydrase VA inhibitors

Publication date: Available online 24 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Edita Čapkauskaitė, Audrius Zakšauskas, Virginijus Ruibys, Vaida Linkuvienė, Vaida Paketurytė, Marius Gedgaudas, Visvaldas Kairys, Daumantas Matulis
The similarity of human carbonic anhydrase (CA) active sites makes it difficult to design selective inhibitors for one or several CA isoforms that are drug targets. Here we synthesize a series of compounds that are based on 5-[2-(benzimidazol-1-yl)acetyl]-2-chloro-benzenesulfonamide (1a) which demonstrated picomolar binding affinity and significant selectivity for CA isoform five A (VA), and explain the structural influence of inhibitor functional groups to the binding affinity and selectivity. A series of chloro-substituted benzenesulfonamides bearing a heterocyclic tail, together with molecular docking, was used to build inhibitors that explore substituent influence on the binding affinity to the CA VA isoform.

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