The Effect of Enzymatically Polymerised Polyphenols on CD4 Binding and Cytokine Production in Murine Splenocytes

High-molecular weight polymerised polyphenols have been shown to exhibit anti-influenza virus, anti-HIV, and anti-cancer activities. The purpose of this study was to evaluate the immunomodulating activities of enzymatically polymerised polyphenols, and to clarify the underlying mechanisms of their effects. The cytokine-inducing activity of the enzymatically polymerised polyphenols derived from caffeic acid (CA), ferulic acid (FA), and p-coumaric acid (CoA) was investigated using murine splenocytes. Polymerised polyphenols, but not non-polymerised polyphenols, induced cytokine synthesis in murine splenocytes. Polymerised polyphenols induced several cytokines in murine splenocytes, with interferon-γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) being the most prominent. The underlying mechanisms of the effects of the polymerised polyphenols were then studied using neutralising antibodies and fluorescent-activated cell sorting (FACS) analysis. Our results show that polymerised polyphenols increased IFN-γ and GM-CSF production in splenocytes. In addition, the anti-CD4 neutralised monoclonal antibody (mAb) inhibited polymerised polyphenol-induced IFN-γ and GM-CSF secretion. Moreover, polymerised polyphenols bound directly to a recombinant CD4 protein, and FACS analysis confirmed that interaction occurs between polymerised polyphenols and CD4 molecules expressed on the cell surface. In this study, we clearly demonstrated that enzymatic polymerisation confers immunoactivating potential to phenylpropanoic acids, and CD4 plays a key role in their cytokine-inducing activity

Accelerated stem cell labeling with ferucarbotran and protamine

To develop and characterize a clinically applicable, fast and efficient method for stem cell labeling with ferucarbotran and protamine for depiction with clinical MRI. The hydrodynamic diameter, zeta potential and relaxivities of ferucarbotran and varying concentrations of protamine were measured. Once the optimized ratio was found, human mesenchymal stem cells (MSCs) were labeled at varying incubation times (1–24 h). Viability was assessed via Trypan blue exclusion testing. 150,000 labeled cells in Ficoll solution were imaged with T1-, T2- and T2*-weighted sequences at 3 T, and relaxation rates were calculated. Varying the concentrations of protamine allows for easy modification of the physicochemical properties. Simple incubation with ferucarbotran alone resulted in efficient labeling after 24 h of incubation while assisted labeling with protamine resulted in similar results after only 1 h. Cell viability remained unaffected. R2 and R2* relaxation rates were drastically increased. Electron microscopy confirmed intracellular iron oxide uptake in lysosomes. Relaxation times correlated with results from ICP-AES. Our results show internalization of ferucarbotran can be accelerated in MSCs with protamine, an approved heparin antagonist and potentially clinically applicable uptake-enhancing agent

Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives

[EN] We introduce a simulation framework for the transport of high and low energy electrons in xenon-based optical time projection chambers (OTPCs). The simulation relies on elementary cross sections (electron-atom and electron-molecule) and incorporates, in order to compute the gas scintillation, the reaction/quenching rates (atom-atom and atom-molecule) of the first 41 excited states of xenon and the relevant associated excimers, together with their radiative cascade. The results compare positively with observations made in pure xenon and its mixtures with CO2 and CF4 in a range of pressures from 0.1 to 10 bar. This work sheds some light on the elementary processes responsible for the primary and secondary xenon-scintillation mechanisms in the presence of additives, that are of interest to the OTPC technology.DGD is supported by the Ramon y Cajal program (Spain) under contract number RYC-2015-18820. The authors want to acknowledge the RD51 collaboration for encouragement and support during the elaboration of this work, and in particular discussions with F. Resnati, A. Milov, V. Peskov, M. Suzuki and A. F. Borghesani. The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the Ministerio de Economia y Competitividad of Spain under grants FIS2014-53371-C04 and the Severo Ochoa Program SEV-2014-0398; the GVA of Spain under grant PROM-ETEO/2016/120; the Portuguese FCT and FEDER through the program COMPETE, project PTDC/FIS-NUC/2525/2014 and UID/FIS/04559/2013; the U.S. Department of Energy under contracts number DE-AC02-07CH11359 (Fermi National Accelerator Laboratory) and DE-FG02-13ER42020 (Texas A& and the University of Texas at Arlington.Azevedo, C.; Gonzalez-Diaz, D.; Biagi, SF.; Oliveira, CAB.; Henriques, CAO.; Escada, J.; Monrabal, F.... (2018). Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives. Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment. 877:157-172. https://doi.org/10.1016/j.nima.2017.08.049S15717287

Mirror therapy: A potential intervention for pain management.

The consequences of chronic pain and associated disabilities to the patient and to the health care system are well known. Medication is often the first treatment of choice for chronic pain, although side effects and high costs restrict long-term use. Inexpensive, safe and easy to self-administer non-pharmacological therapies, such as mirror therapy, are recommended as adjuncts to pain treatment. The purpose of this review is to describe the principles of use of mirror therapy so it can be incorporated into a health care delivery. The physiological rationale of mirror therapy for the management of pain and the evidence of clinical efficacy based on recent systematic reviews are also discussed. Mirror therapy, whereby a mirror is placed in a position so that the patient can view a reflection of a body part, has been used to treat phantom limb pain, complex regional pain syndrome, neuropathy and low back pain. Research evidence suggests that a course of treatment (four weeks) of mirror therapy may reduce chronic pain. Contraindications and side effects are few. The mechanism of action of mirror therapy remains uncertain, with reintegration of motor and sensory systems, restored body image and control over fear-avoidance likely to influence outcome. The evidence for clinical efficacy of mirror therapy is encouraging, but not yet definitive. Nevertheless, mirror therapy is inexpensive, safe and easy for the patient to self-administer

The role of molecular state and orientation in harpooning reactions: N2O on Cs/Pt(111)

Brandt M, Greber T, Bowering N, Heinzmann U. The role of molecular state and orientation in harpooning reactions: N2O on Cs/Pt(111). PHYSICAL REVIEW LETTERS. 1998;81(11):2376-2379.The interaction of a beam of state selected and oriented N2O molecules with 1 ML of Cs on Pt(lll) is studied by means of exoelectron emission. While the immediate emission is absent for the impact of ground-state molecules it is present when the molecules are in the first excited n(2) = 1 vibrational bending mode. The observed orientational anisotropy agrees with a theory that includes the molecular orientation. The results can be explained in a picture where N2O approaches the surface with the O end and where-after harpooning-an exoelectron is emitted

SPECTRAL DIAGNOSIS OF A LASER-PRODUCED XUV SOURCE USING A DIGITAL CAMERA SYSTEM WITH PINHOLE TRANSMISSION GRATING

BOWERING N, DOHRING T, GARNER U, Heinzmann U. SPECTRAL DIAGNOSIS OF A LASER-PRODUCED XUV SOURCE USING A DIGITAL CAMERA SYSTEM WITH PINHOLE TRANSMISSION GRATING. In: Laser and Particle Beams. LASER AND PARTICLE BEAMS. Vol 9. CAMBRIDGE UNIV PRESS; 1991: 593-601.For spectral diagnosis, a repetitive laser-produced soft-X-ray source was examined in the range 2-40 nm using a spectrometer containing a pinhole transmission grating, an image converter, and a CCD camera. Via digital recording the detection system provides fast on-line data accumulation with spectral and spatial resolution. With this detector the performance of the light source was studied with respect to spectral emission characteristics, long-term stability, and reproducibility by recording spectra for different solid targets and liquid lead