Application of Spin Labels for Research of Vanadyl Acetylacetonate Concentration in Model Bilayer Membranes by EPR Spectroscopy

The compounds and complexes of vanadium are used to treat diabetes and cancer. Research on the effectiveness and mechanism of action of new derivatives of vanadium, and their toxicity is currently very intense. The research shows that the vanadium(IV) acetylacetonate complex [VO(acac)2] shows a synergism with insulin in treating diabetes, high pharmacological activity and low toxicity. In order to improve the effectiveness of drugs and minimize their toxicity, the active compounds are often closed in the liposome membranes. The objective of the work was preparation of bilayer liposomes from egg yolk phosphatidylcholine (EYPC), closing the complex VO(acac)2 in these membranes and estimating the concentration of vanadium complex after incorporation into liposomes membranes. Due to the paramagnetic properties of vanadium(IV) the concentration of this metal complex can be determined directly by EPR. Entering the spin label CTPO in the water phase into the studied arrangement allows for the indirect measurement of the concentration of complex, on the basis of changes of the EPR spectrum of the spin label caused by the presence of the vanadium(IV) complex. In the work the dependence of the α parameter based on the analysis of CTPO EPR spectra on the concentration of VO(acac)2 was determined. To demonstrate the presence of the complex in the membrane directly by measuring the EPR sulfate(IV) sodium was used in order to remove the EPR signal of vanadium(IV) from the water phase. The presence of vanadium(IV) in the membrane was also demonstrated indirectly using a spin label 12-SASL. Based on the results of EPR spectroscopy the concentration of the complex in the membrane was determined together with the partition coefficient of VO(acac)2 between the membrane and outer water environment of the membrane

The Effect of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Hereditary Spastic Paraplegia

Background. Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited disorders affecting predominantly the motor cortex and pyramidal tract, which results in slowly progressing gait disorders, as well as spasticity and weakness of lower extremities. Repetitive transcranial magnetic stimulation (rTMS) has been previously investigated as a therapeutic tool for similar motor deficits in a number of neurologic conditions. The aim of this randomized, controlled trial was to investigate the therapeutic potential of rTMS in various forms of HSP, including pure and complicated forms, as well as adrenomyeloneuropathy. Methods. We recruited 15 patients (five women and 10 men; mean age 43.7±10.6 years) with the mentioned forms of HSP. The intervention included five sessions of bilateral 10 Hz rTMS over primary motor areas of the muscles of lower extremities and five sessions of similar sham stimulation. Results. One patient dropped out due to seizure, and 14 patients completed the study protocol. After real stimulation, the strength of the proximal and distal muscles of lower extremities increased, and the spasticity of the proximal muscles decreased. Change in spasticity was still present during follow-up assessment. No effect was observed regarding gait velocity. No changes were seen after sham stimulation. A post hoc analysis revealed an inverse relation between motor threshold and the change of the strength after active rTMS. Conclusions. rTMS may have potential in improving weakness and spasticity of lower extremities in HSP, especially of proximal muscles whose motor areas are located more superficially. This trial is registered with Clinicaltrials.gov NCT03627416