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Preclinical validation of a novel oral Edaravone formulation for treatment of frontotemporal dementia

Research Abstract

Oxidative stress is a key factor in the pathogenesis of several neurodegenerative disorders and is involved in the accumulation of amyloid beta plaques and Tau inclusions. Edaravone (EDR) is a free radical scavenger that is approved for motor neuron disease and acute ischemic stroke. EDR alleviates pathologies and cognitive impairment of AD via targeting multiple key pathways in transgenic mice. Herein, we aimed to study the effect of EDR on Tau pathology in P301L mice; an animal model of frontotemporal dementia (FTD), at two age time points representing the early and late stages of the disease. A novel EDR formulation was utilized in the study and the drug was delivered orally in drinking water for 3 months. Then, behavioral tests were conducted followed by animal sacrifice and brain dissection. Treatment with EDR improved the reference memory and accuracy in the probe trial as evaluated in Morris water maze, as well as novel object recognition and significantly alleviated motor deficits in these mice. EDR also reduced the levels of 4-hydroxy-2-nonenal and 3-nitrotyrosine adducts. In addition, immunohistochemistry showed that EDR reduced tau phosphorylation and neuroinflammation and partially rescued neurons against oxidative neurotoxicity. Moreover, EDR attenuated downstream pathologies involved in Tau hyperphosphorylation. These results suggest that EDR may be a potential therapeutic agent for the treatment of FTD.

Research Authors
Sally Kelliny, Jing Xiong, Larisa Bobrovskaya, Xin-Fu Zhou
Research Date
Research Journal
Neurotoxicity Research
Research Member
Research Publisher
Springer Nature
Research Rank
Q2
Research Website
https://doi.org/10.1007/s12640-021-00405-2
Research Year
2021

Preclinical study of the pharmacokinetics of p75ECD-Fc, a novel human recombinant protein for treatment of Alzheimer’s disease, in Sprague Dawley rats

Research Abstract

p75ECD-Fc is a recombinant human protein that has recently been developed as a novel therapy for Alzheimer’s disease. Current studies showed that it is able to alleviate Alzheimer’s disease pathologies in animal models of dementia. Thus, knowledge about the pharmacokinetic behavior and tissue distribution of this novel protein is crucial in order to better understand its pharmacodynamics and more importantly for its clinical development.

Research Authors
Sally Kelliny, Ho Y Lam, Ankit Parikh, Yan-Jiang Wang, Larisa Bobrovskaya, Richard Upton, Xin-Fu Zhou
Research Date
Research Department
Research Journal
Current drug metabolism
Research Member
Research Publisher
Bentham Science Publishers
Research Rank
Q2
Research Vol
21
Research Website
https://doi.org/10.2174/1389200221666200502015203
Research Year
2020

Towards understanding of different solid forms of formoterol fumarate: Combined computational and experimental approach

Research Abstract

In this study, specimens of Formetrol fumerate were investigated using IR and Raman vibrational spectroscopy as well as quantum chemical calculations. The structure of formetrol fumerate was optimised using density functional theory calculations and the geometry optimization has been carried out on three different solvate crystal forms; di-hydrate, di-ethanolate, and di-isopropanolate in addition to the anhydrate form with and without intramolecular hydrogen bonding. Molecular assignments are proposed on the basis of ab initioB3LYP DFT calculations with a 6–31 G∗ basis set and vibrational wavenumbers. Crystallographic investigation has been carried out to formetrol anions and protonated anions arising from crystal structures of the studied conformers and it was evidenced that the di-hydrate form has the highest energy probably due to the greater possibility of intramolecular hydrogen bonding. Infrared and Raman spectra were calculated from the optimised structures. Many modes in the calculated spectra were matched with the experimental spectra and a description of the modes was given. By analysis of the theoretical vibrational modes, it was proved that formetrol fumerate specimens are likely to be dihydrate form with and without intramolecular hydrogen bonding. Additionally, several spectral features and band intensities in the stretching and bending regions were explained. Quantum mechanical calculations allowed improved understanding of formetrol fumerate and its vibrational spectra as an important β2 antagonistic compound in various pharmaceutical formulations. The obtained data could provide useful information about its interactions with excipients and other components.

Research Authors
Ahmed FariedAbdel Hakiem, J.Kendrick, Hassan Refat H. Ali
Research Date
Research Journal
Vibrational Spectroscopy
Research Member
Research Publisher
Elsevier
Research Vol
110
Research Website
https://doi.org/10.1016/j.vibspec.2020.103132
Research Year
2020

Innovative computationally designed-spectrofluorimetric method for determination of modafinil in tablets and human plasma

Research Authors
Noha M. Hosny; Mohammed I. Gadallah; Rosa M. Gomila; Wesam S. Qayed
Research Date
Research Journal
Talanta
Research Publisher
Science-Direct
Research Rank
Q1
Research Vol
236 (122890)
Research Website
https://www.sciencedirect.com/science/article/abs/pii/S0039914021008110
Research Year
2021

Preparation and evaluation of spray dried rosuvastatin calcium-PVP microparticles for the improvement of serum lipid profile

Research Abstract

The poor physicochemical properties of rosuvastatin calcium (ROS) remains a challenge for dosage form development. In the present study, we explore the development of spray dried ROS loaded PVP microparticles to improve the release of ROS as well as the anti-hyperlipidemic efficacy. The ROS loaded PVP microparticles (F1–F3)were developed byspraydryingmethod witharangeofparticle size(1.26–1.67μm), PDI(0.138-0.267), PDE (78 ± 3.2 to 89 ± 4.1%), PDL and (14.8 ± 1.2 to 39.4 ± 3.3%). The ROS loaded microparticles (F3) was optimized based on preliminary characterization and further evaluated for DSC, FTIR, SEM, in vitro release studies and anti-hyperlipidemic activity. Overall, It was proved that spray dried PVP microparticles was efficient carrier to deliver rosuvastatin with improved serum lipid profile of hyperlipidemic rats.
 

Research Authors
Ramadan Al-Shdefat, Md Khalid Anwer,∗, Mohamed H. Fayed, Badar B. Alsulays, Hesham M. Tawfeek, Rehab F. Abdel-Rahman, Gamal A. Soliman
Research Date
Research Department
Research File
3.pdf (1.92 MB)
Research Journal
Journal of drug delivery science and technology
Research Publisher
Elsevier
Research Rank
Q2
Research Vol
55
Research Website
https://doi.org/10.1016/j.jddst.2019.101342
Research Year
2019

Loganin-type iridoids as chemotaxonomic markers in Glandularia gooddingii (Briq.) Solbrig‏

Research Abstract

 

Glandularia is one of the genera that has few published phytochemical studies and, for many years, it was considered to be within the genus Verbena. Verbena is known to be rich in iridoids, flavonoids, and phenylpropanoids. Three iridoid glucosides, 6β-hydroxyipolamiide, phlomiol, and pulchelloside I were isolated from the methanolic extract of the whole plant of Glandularia gooddingii (Briq.) Solbrig and elucidated by extensive analysis of the 1D- and 2D-NMR as well as by HR-ESI-QTOF mass spectra. Identification of these iridoids and determining their chemical nature supports the chemotaxonomic classification of the genus Glandularia and defines certain members belonging to it. This is the first report of the X-ray crystal structure of 6β-hydroxyipolamiide

Research Authors
, Mai A.M. Ahmed, Nesma M. Mohamed, Timothy J. Woodman Gabriele Kociok-KohnIan I.S. Blagbrough
Research Date
Research Journal
Phytochemistry Letters
Research Vol
44
Research Year
2021

Analgesic Effect of Morphine Added to Bupivacaine in Serratus Anterior Plane Block Following Modified Radical Mastectomy. Only a Local Effect? Randomized Clinical Trial

Research Abstract

Background

Serratus anterior plane (SAP) block, a novel regional anesthetic procedure, involves the anterolateral chest wall. Opioid receptors have been found on peripheral nerve terminals, so morphine may have a local action.

Objective

This work aimed at exploring the analgesic efficacy of morphine added to bupivacaine in SAPB in patients for whom modified radical mastectomy was conducted and whether it is a mere local effect.

Methods

Forty female patients were planned to have modified radical mastectomy participated in the study. Patients were randomly divided into two groups; Control group (C): received ultrasound-guided serratus anterior plane block with 20 mL of bupivacaine hydrochloride 0.25%; Morphine group (M): received the same in addition to 10 mg morphine sulfate. Intra-and post-operative blood samples were taken for the assessment of morphine serum levels. All patients were assessed for …

Research Authors
Fatma A El Sherif, Ahmad M Abd El-Rahman, Ahmed H Othman, Samia A Shouman, Mervat M Omran, Nivin A Hassan, Sahar B Hassan, Ebrahim Aboeleuon
Research Date
Research Department
Research Journal
Journal of pain research
Research Member
Research Publisher
Dove Press
Research Vol
13
Research Year
2020
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