EMG Map for Designing the Electrode Shape for Functional Electrical Therapy of Upper Extremities

Achieving the functional grasp by electrical stimulation using surface electrodes is a demanding task. The innervations of muscles come via ulnar, radial and median nerves. The anatomy of nerve branches connecting various muscles in the forearm differs significantly between individuals. We hypothesize that the anatomical differences between the paretic and nonparetic arms are minimal. Based on this assumption we developed a method where the differences of muscle activities (EMG) between the healthy and paretic arms recorded by the 24-contact electrode within an array define the target zones to be stimulated on the affected forearm. We used special electrode where magnetic contacts allow simple change of the stimulation pads. The examiner positions the magnetic contact on the pads where the EMG differences are maximal. The stimulator delivers asynchronous stimulation to the selected pads. We proved that the method is working in stroke patients by measuring joint angles and the grasping force. © 2019, Springer Nature Switzerland AG.Biosystems and Biorobotics, Vol. 21This is the peer-reviewed version of the following article: Popović-Maneski, L., Topalović, I., 2019. EMG Map for Designing the Electrode Shape for Functional Electrical Therapy of Upper Extremities, in: Masia, L., Micera, S., Akay, M., Pons, J.L. (Eds.), Converging Clinical and Engineering Research on Neurorehabilitation III, Biosystems & Biorobotics. Springer International Publishing, pp. 1003–1007, http://dx.doi.org/10.1007/978-3-030-01845-0_20

The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization

This study shows the potential of a thermally induced human serum albumin (HSA) hydrogel to serve as a drug depot for sustained release of a highly cytotoxic modified paullone ligand bearing a TEMPO free radical (HL). The binding of HL to HSA was studied by electron paramagnetic resonance (EPR) spectroscopy and imaging. The EPR protocol was also implemented for the study of matrix degradation, and ligand diffusion rate, in two additional spin-labeled hydrogels, containing 5-doxylstearate and 3-carbamoyl-proxyl. The results showed that the hydrogel is an efficient HL reservoir as it retained 60% of the ligand during 11 days of dialysis in physiological saline. Furthermore, upon incubation with Colo 205 human colon adenocarcinoma cells for 3 days, the HL/HSA hydrogel did not exhibit cytotoxic activity, demonstrating that it is also an efficient ligand depot in the presence of living cells. It was observed that the percentage of HL release is independent of its initial concentration in the hydrogel, suggesting that HSA possesses a specific binding site for the ligand, most likely Sudlow site 2, as predicted by molecular docking. The intrinsic property of albumin to bind and transport various substances, including hydrophobic drugs, may be fine-tuned by appropriate physical/chemical hydrogel preparation procedures, providing optimal drug delivery

Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition

Three new thiosemicarbazones (TSCs) HL1–HL3 as triapine analogues bearing a redox-active phenolic moiety at the terminal nitrogen atom were prepared. Reactions of HL1–HL3 with CuCl2·2H2O in anoxic methanol afforded three copper(II) complexes, namely, Cu(HL1)Cl2 (1), [Cu(L2)Cl] (2′), and Cu(HL3)Cl2 (3), in good yields. Solution speciation studies revealed that the metal-free ligands are stable as HL1–HL3 at pH 7.4, while being air-sensitive in the basic pH range. In dimethyl sulfoxide they exist as a mixture of E and Z isomers. A mechanism of the E/Z isomerization with an inversion at the nitrogen atom of the Schiff base imine bond is proposed. The monocationic complexes [Cu(L1–3)]+ are the most abundant species in aqueous solutions at pH 7.4. Electrochemical and spectroelectrochemical studies of 1, 2′, and 3 confirmed their redox activity in both the cathodic and the anodic region of potentials. The one-electron reduction was identified as metal-centered by electron paramagnetic resonance spectroelectrochemistry. An electrochemical oxidation pointed out the ligand-centered oxidation, while chemical oxidations of HL1 and HL2 as well as 1 and 2′ afforded several two-electron and four-electron oxidation products, which were isolated and comprehensively characterized. Complexes 1 and 2′ showed an antiproliferative activity in Colo205 and Colo320 cancer cell lines with half-maximal inhibitory concentration values in the low micromolar concentration range, while 3 with the most closely related ligand to triapine displayed the best selectivity for cancer cells versus normal fibroblast cells (MRC-5). HL1 and 1 in the presence of 1,4-dithiothreitol are as potent inhibitors of mR2 ribonucleotide reductase as triapine