Introduction to Oxidative (Eu)stress in Exercise Physiology
James N. Cobley, Gareth W. Davison in Oxidative Eustress in Exercise Physiology, 2022
The discovery that free radicals (i.e., molecules capable of existing independently, and containing one or more unpaired electrons) exist in living biological organisms occurred in 1954 when Commoner and colleagues (Commoner et al., 1954) first used electron paramagnetic resonance (EPR) spectroscopy to detect free radicals in growing seeds. Around this time, Gerschman et al. (1954) proposed that free radicals damage cells, and second, when mice are exposed to hyperoxia, the biological injury that ensues is likely related to increased free radical production. Following the publication of this work in the mid-1950s, a series of seminal studies confirmed the biological importance (Powers et al., 2016). For example, the work of Chance and Williams (1956) demonstrated that respiring mitochondria can generate hydrogen peroxide, which can diffuse in cells. Then, McCord and Fridovich (1969) discovered the metalloenzyme superoxide dismutase (SOD), showing in the process that superoxide radicals are spontaneously degraded to hydrogen peroxide. The milestone discovery of SOD not only provided much of the basis of our current understanding of antioxidant defence systems, but it is also credited with providing the first convincing evidence that biological reactive oxygen species (ROS) exist and that they are likely salient regulators of cell biology (Powers et al., 2016).
Narcotic Analgesics And Antagonists
S.J. Mulé, Henry Brill in Chemical and Biological Aspects of Drug Dependence, 2019
Unfortunately, this conformational resemblance is based on an axially oriented phenyl group. The x-ray structure determination of dl-alphaprodine hydrochloride, a related compound, proved that the phenyl group existed in an equatorial conformation in the solid state (see Formula 20) in alphaprodine and, by analogy, in pethidine itself. However, it is now fairly well accepted that both a macromolecule which contains the receptor site, and a small drug molecule can interact and influence the conformation of the other. Whether such interaction can induce inversion through the boat form of pethidine’s piperi-dine ring to a conformation of the pethidine molecule which might satisfy the unknown morphine receptor is, again, speculation. It would be helpful if information could be obtained about the macromolecule, or macromolecular system, with which analgesics interact to produce their biological effect. At least a rational start could then be made towards the determination of actual binding sites using, perhaps, the contemporary methods of electron paramagnetic resonance spectroscopy,32 nuclear magnetic resonance spectroscopy,33,34 and fluorescent antibody techniques.35,36
Physicochemical Principles of MR Contrast Agents
Michel M. J. Modo, Jeff W. M. Bulte in Molecular and Cellular MR Imaging, 2007
There are no inner-sphere water molecules in iron particles, and relaxation of water arises from the water molecules diffusing near the particle. However, the mechanism of outer-sphere relaxation is different than described above. One feature is that the crystals have a net magnetization, and as the external field is increased, this magnetization is increased (this is true as well for Gd, but the effect is much smaller). The modulation of this net magnetization can cause proton relaxation (so-called Curie spin relaxation). The theories describing the field dependence of iron oxide relaxivity have been reported.33 Solvent relaxation induced by iron oxide systems is complex. Bulte et al.34,35 used a combination of variable field T2 measurements (T2 relaxometry), electron paramagnetic resonance (EPR), and magnetization measurements to fully characterize one such USPIO, MION-46L. To fully explain their experimental findings, they proposed the existence of three different magnetic phases for this USPIO: a superparamagnetic core, an antiferromagnetic ferritin-like phase of incompletely converted iron oxyhydroxide, and a paramagnetic surface effect of ferric ions.
Application of EPR spectroscopy to examine free radicals evolution during storage of the thermally sterilized Ungentum ophthalmicum
Published in Pharmaceutical Development and Technology, 2018
Electron paramagnetic resonance (EPR) spectroscopy is the method to examine paramagnetic molecules or chemical structures with unpaired electrons, especially free radicals1,2. Diamagnetic units may be tested by EPR after introducing by spin-labels1. EPR is applied in the characterization of free radicals ophthalmology3–7. Free radicals, as the active molecules, modify and damage eye structures4–7. High amounts of o-semiquinone free radicals existed in melanin in the epithelial melanosomes4. Light irradiation produced free radicals in the human retinal lipofuscin5. Drugs applied on eye should not contain free radicals, which were responsible for toxic effects2,8–10. It was presented by us that free radicals were formed during thermal sterilization of drugs11–13 and pharmaceutical bases14–16.
Drug stability testing and formulation strategies
Published in Pharmaceutical Development and Technology, 2018
Guidelines for stability testing on drug substances or products are provided by the International Conference on Harmonization (ICH) as Q1A (R2) guidelines and recently World Health Organization (WHO) as TRS1010 Annex 10. The analytical methods should be reliable and ‘stability-indicating’ to demonstrate the stability of a drug substance or product under the influence of a variety of environmental factors. Whilst the use of high performance liquid chromatography is predominant for stability testing, a range of other techniques are needed for drug analysis and to understand the various mechanisms of degradation. This Special Edition of PDT features the use of electron paramagnetic resonance spectroscopy, which can provide insight into free radical formation and their effect on drug stability in pharmaceutical dosage forms.
Current trends in PLGA based long-acting injectable products: The industry perspective
Published in Expert Opinion on Drug Delivery, 2022
Omkara Swami Muddineti, Abdelwahab Omri
This review provides a comprehensive overview of PLGA-based LAI as per the pharmaceutical industry perspective. Attention is needed to focus on analytical methods, physicochemical, and characterization to recognize appropriate CQAs that need to be matched during generic product development. Using advanced modeling parameters, further research should be focused on formulation and critical process parameters to set appropriate control strategies for successful scale-up, commercialization, and in vivo product performance. Hence, in vitro characterization has to be investigated thoroughly to predict in vivo performance, which helps in bioequivalence studies. To develop relevant in vitro predictive models for ISF implants, reliable technologies should be explored for understanding critical parameters such as phase separation, implant formation, degradation, drug release, etc. Different techniques such as electron paramagnetic resonance spectroscopy, ultrasound imaging techniques, UV-visible imaging, fluorescence imaging, diffusion-weighted magnetic resonance imaging, etc., helps in the understanding of the parameters mentioned.
Related Knowledge Centers
- Absorption
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