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Future problems you can anticipate
Published in Nicola T Shaw, Computerization and Going Paperless in Canadian Primary Care, 2018
It is a fact of computerized EPR systems that however much training you have you will always need more. Just like other software applications many people never use more than 10% of the capability of an EPR system as they either don’t know how to or don’t know what is possible. The only way to make really effective use of your system is to really consider what you want from it (Part Two) and then to arrange a program of training for all the practice team that will allow you to meet your needs.
Electron spin resonance of skin
Published in Roger L. McMullen, Antioxidants and the Skin, 2018
Electron spin resonance (ESR), also known as electron paramagnetic resonance (EPR), is a unique research tool that can directly identify free radicals and measure their concentration. It is a technique based on fundamental quantum physics that has found widespread application in the analysis of skin. In most studies, skin biopsies or homogenates are used for analysis. However, in vivo data may be collected by making special adjustments during the operation of the ESR instrument. Regardless, far less work has been completed in vivo—probably due to limited sensitivity. ESR can directly detect endogenous long-lived (persistent) free radicals in skin, such as the ascorbate and melanin radicals. By monitoring their concentration, we can subject the sample, directly in the instrument, to treatments or stresses such as UV irradiation and monitor the formation or reduction of radical species. Moreover, ESR can provide information about the overall redox state of skin—for example, how many radicals are present. ESR can also furnish data regarding the degree of oxygenation of tissues (oximetry) and the biophysical properties of lipid membrane structures.1 In most cases, this type of data is generated using nitroxide probes (nitroxyl spin labels)—stable radicals that are not easily metabolized. Thus, they react with and incorporate themselves into the structure of radical biological species and serve as an indicator of the redox state of the tissue.
The Spin Trapping of Superoxide Radicals
Published in Robert A. Greenwald, CRC Handbook of Methods for Oxygen Radical Research, 2018
Paul J. Thornalley, Joe V. Bannister
EPR is considered to be the least ambiguous method for the detection of free radicals. However, even when concentrations of O2− exceed those normally required for detection (10−8M), no EPR spectrum is observed in aqueous solution under physiological conditions. This is due to the very short relaxation time of the O2− resonance (due to strong “spin orbital coupling”). A decrease in sample temperature may redress this effect, but this usually negates any physiologically significant kinetic and possibly structural aspects in the EPR spectrum. However, spin trapping allows the formation of stable free radical products, thereby allowing their detection. Superoxide radicals in the presence of nitrones form stable products known as spin adducts which are paramagnetic and have an EPR spectrum.
Factors affecting the dynamics and heterogeneity of the EPR effect: pathophysiological and pathoanatomic features, drug formulations and physicochemical factors
Published in Expert Opinion on Drug Delivery, 2022
Rayhanul Islam, Hiroshi Maeda, Jun Fang
Still, the development of anticancer nanomedicines for solid tumors continues to be challenging, and the clinical outcome is far from ideal because of a number of critical problems, such as those seen with, for instance, PK1, PK2, NK911, and Doxil®. First, to achieve tumor-selective drug delivery and then drug entry into tumor cells, one crucial issue concerns tumor blood flow, which is responsible for the heterogeneity of the EPR effect. The EPR effect occurs only in the presence of adequate blood flow. If blood flow is obstructed, drugs (nanomedicines) cannot reach tumor tissues. Many patients are now known to have elevated levels of thrombin formation and therefore obstructed blood flow. For example, the possibility of tumor blood vessel occlusion increased 5- to 6-fold in patients who had an earlier (2 months) diagnosis of cancer compared with matched controls without cancer [17,18]. Thus, when tumor blood vessel occlusion occurs in such patients, anticancer drugs cannot reach the tumors, and no successful therapeutic effect is possible. Overcoming the heterogeneity of the EPR effect and improving tumor blood flow are thus becoming key issues for achieving better therapeutic effects in clinical settings.
NiONPs-induced alteration in calcium signaling and mitochondrial function in pulmonary artery endothelial cells involves oxidative stress and TRPV4 channels disruption
Published in Nanotoxicology, 2022
Ophélie Germande, Magalie Baudrimont, Fabien Beaufils, Véronique Freund-Michel, Thomas Ducret, Jean-François Quignard, Marie-Hélène Errera, Sabrina Lacomme, Etienne Gontier, Stéphane Mornet, Megi Bejko, Bernard Muller, Roger Marthan, Christelle Guibert, Juliette Deweirdt, Isabelle Baudrimont
Superoxide anion production was measured using the spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH, Noxygen®) according to the manufacturer’s recommendations and as previously described (Deweirdt et al. 2017). EPR spin trapping is one of the specific techniques used to study free radical production such as the superoxide anion. However, the very short life span and the relatively low concentration of superoxide anion (O2˙ˉ) made the measurement difficult to develop. The CMH probe has the property of being soluble and makes it possible to measure intracellular O2˙ˉ (Dikalov et al. 2011; Konczol et al. 2012). Moreover, the CMH probe can be oxidized by O2˙ˉ to generate a stable nitroxide radical (CM•) easily detectable by EPR spectroscopy. After a 4 h-exposure to NiONPs, cells were incubated for 20 min with the spin-probe mix containing CMH (500 µM), diethyldithiocarbamate (5 µM), and deferoxamine (25 µM) in KHB solution. Then, HPAEC were scraped, homogenized, and frozen in a syringe in liquid nitrogen before EPR analysis. All the EPR spectra were recorded using the Spectrometer X Miniscope MS200 (Magnettech®, Germany). The EPR parameters have been previously described (Deweirdt et al. 2017). Following EPR spectra readings, protein quantities were measured by a Lowry test (Lowry reagent, Sigma Aldrich®), according to the manufacturer’s recommendations. The results were normalized to protein quantities and expressed as EPR signal amplitudes in arbitrary units (AU)/mg of protein.
Application of PLGA nano/microparticle delivery systems for immunomodulation and prevention of allotransplant rejection
Published in Expert Opinion on Drug Delivery, 2020
Sanaz Keshavarz Shahbaz, Farshad Foroughi, Ehsan Soltaninezhad, Tannaz Jamialahmadi, Peter E. Penson, Amirhossein Sahebkar
The burst release of the drugs from PLGA matrices due to rapid diffusion of protein adsorbed at the surface of the polymer and high mobility of drug molecule during the hydration of PLGA is another problem associated with PLGA based nanoparticle delivery. It has been demonstrated that the application of certain additives, including PEG 400 can resolve this problem by improving the stability of encapsulated drugs [107]. Additionally, the enhanced permeability and retention (EPR) effect is often misunderstood as one of the major drawbacks of this system. EPR is a heterogeneous phenomenon that differs from model to model, and from patient to patient. Active drug targeting to improve EPR is not very effective due to immunogenicity and protein adsorption following the introduction of targeting moieties [112]. PLGA-based nanoparticles are associated with weak drug loading, despite having high encapsulation efficiency. This results in increased costs of production and difficulties in scaling production [113,114].