Neurophysiological Predictors of Response to Medication in Parkinson's Disease

Background: Although dopaminergic medication has been the foundation of Parkinson's disease (PD) therapy for decades, sensitive and specific therapeutic response biomarkers that allow for better treatment optimization are lacking. Objective: We tested whether the features of Transcranial Magnetic Stimulation-based neurophysiological measures taken off-medication are associated with dopaminergic medication-induced clinical effects. Method: Motor cortex excitability [short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), and input-output (IO) curve], and plasticity [paired associative stimulation (PAS) protocol] neurophysiological measures were examined in 23 PD patients off-medication. Clinical features were quantified by the motor section of the Unified Parkinson's Disease Scale (total score and lateralized total, bradykinesia, and rigidity sub-scores), and the differences between measures off-medication and on-medication (following the usual morning dose), were determined. Total daily dopaminergic medication dose (expressed as levodopa equivalent daily dose-LEDD), was also determined. Results: SICI significantly correlated with changes in lateralized UPDRS motor and bradykinesia sub-scores, suggesting that patients with stronger basal intracortical inhibition benefit more from dopaminergic treatment than patients with weaker intracortical inhibition. Also, ICF significantly negatively correlated with LEDD, suggesting that patients with stronger intracortical facilitation require less dopaminergic medication to achieve optimal therapeutic benefit. Both associations were independent of disease severity and duration. Conclusions: The results suggest variability of (patho) physiological phenotypes related to intracortical inhibitory and facilitatory mechanisms determining clinical response to dopaminergic medication in PD. Measures of intracortical excitability may help predict patients' response to dopaminergic therapy, thus potentially providing a background for developing personalized therapy in PD

Supplementary data for the article: Filipović, N. R.; Marković, I.; Mitić, D.; Polović, N.; Milčić, M.; Dulović, M.; Jovanović, M.; Savić, M.; Nikšić, M.; Andelković, K.; et al. A Comparative Study of In Vitro Cytotoxic, Antioxidant, and Antimicrobial Activity of Pt(II), Zn(II), Cu(II), and Co(III) Complexes with N-Heteroaromatic Schiff Base (E)-2-[N’-(1-Pyridin-2-Yl-Ethylidene)Hydrazino]Acetate. Journal of Biochemical and Molecular Toxicology 2014, 28 (3), 99–110. https://doi.org/10.1002/jbt.21541

Supplementary material for: [https://doi.org/10.1002/jbt.21541]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1509

Supplementary data for article: Božić, A. R.; Filipović, N. R.; Verbić, T.; Milčić, M. K.; Todorović, T.; Cvijetić, I.; Klisurić, O.; Radišić, M.; Marinković, A. A Detailed Experimental and Computational Study of Monocarbohydrazones. Arabian Journal of Chemistry 2020. https://doi.org/10.1016/j.arabjc.2017.08.010

Supplementary material for: [https://www.sciencedirect.com/science/article/pii/S1878535217301661?via%3Dihub]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/318

Supplementary data for the article: Filipović, N. R.; Marković, I.; Mitić, D.; Polović, N.; Milčić, M.; Dulović, M.; Jovanović, M.; Savić, M.; Nikšić, M.; Andelković, K.; et al. A Comparative Study of In Vitro Cytotoxic, Antioxidant, and Antimicrobial Activity of Pt(II), Zn(II), Cu(II), and Co(III) Complexes with N-Heteroaromatic Schiff Base (E)-2-[N’-(1-Pyridin-2-Yl-Ethylidene)Hydrazino]Acetate. Journal of Biochemical and Molecular Toxicology 2014, 28 (3), 99–110. https://doi.org/10.1002/jbt.21541

Supplementary material for: [https://doi.org/10.1002/jbt.21541]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1509

Supplementary material for the article: Wedmann, R.; Onderka, C.; Wei, S.; Szijártó, I. A.; Miljkovic, J. L.; Mitrovic, A.; Lange, M.; Savitsky, S.; Yadav, P. K.; Torregrossa, R.; et al. Improved Tag-Switch Method Reveals That Thioredoxin Acts as Depersulfidase and Controls the Intracellular Levels of Protein Persulfidation. Chemical Science 2016, 7 (5), 3414–3426. https://doi.org/10.1039/c5sc04818d

Supplementary material for: [https://doi.org/10.1039/c5sc04818d]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1925

Supplementary data for article: Snijder, P. M.; Baratashvili, M.; Grzeschik, N. A.; Leuvenink, H. G. D.; Kuijpers, L.; Huitema, S.; Schaap, O.; Giepmans, B. N. G.; Kuipers, J.; Miljkovic, J. L.; et al. Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3. Molecular Medicine 2015, 21, 758–768. https://doi.org/10.2119/molmed.2015.00221

Supplementary material for: [https://doi.org/10.2119/molmed.2015.00221]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2255

Supplementary data for article: Snijder, P. M.; Baratashvili, M.; Grzeschik, N. A.; Leuvenink, H. G. D.; Kuijpers, L.; Huitema, S.; Schaap, O.; Giepmans, B. N. G.; Kuipers, J.; Miljkovic, J. L.; et al. Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3. Molecular Medicine 2015, 21, 758–768. https://doi.org/10.2119/molmed.2015.00221

Supplementary material for: [https://doi.org/10.2119/molmed.2015.00221]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2255

Consequences of MnSOD interactions with nitric oxide: Nitric oxide dismutation and the generation of peroxynitrite and hydrogen peroxide

The present study demonstrates that manganese superoxide dismutase (MnSOD) Escherichia coli, binds nitric oxide (NO) and stimulates its decay under both anaerobic and aerobic conditions. The results indicate that previously observed MnSOD-catalyzed NO disproportionation (dismutation) into nitrosonium (NO + ) and nitroxyl (NO - ) species under anaerobic conditions is also operative in the presence of molecular oxygen. Upon sustained aerobic exposure to NO, MnSOD-derived NO - species initiate the formation of peroxynitrite (ONOO - ) leading to enzyme tyrosine nitration, oxidation and (partial) inactivation. The results suggest that both ONOO - decomposition and ONOO - -dependent tyrosine residue nitration and oxidation are enhanced by metal centre-mediated catalysis. We show that the generation of ONOO - is accompanied by the formation of substantial amounts of H 2 O 2 . MnSOD is a critical mitochondrial antioxidant enzyme, which has been found to undergo tyrosine nitration and inactivation in various pathologies associated with the overproduction of NO. The results of the present study can account for the molecular specificity of MnSOD nitration in vivo. The interaction of NO with MnSOD may represent a novel mechanism by which MnSOD protects the cell from deleterious effects associated with overproduction of NO

Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus)

The aim of this study was to identify palatable additives which have a significant protective action against soft tissue changes in the oral cavity caused by Swedish smokeless tobacco (snus), and that satisfy existing legal requirements. Although the cancer risk from snus is extremely low, long term use may result in highly undesirable keratotic lesions and associated epithelial abnormalities in the oral cavity. The rat forestomach, which is vulnerable to the irritative action of non-genotoxic compounds like butylated hydroxyanisole, propionic acid as well as snus, was chosen as an experimental model. Studied toxicological endpoints included histopathology and cellular proliferation based on DNA incorporation of bromodeoxyuridine. After 6 weeks exposure, blueberries (bilberries) and an extract from the common milk thistle were found to exert a highly significant inhibition of cell proliferation induced by snus in the rat forestomach epithelium, indicating a potential protection with respect soft tissue changes in the human oral cavity. (C) 2016 Elsevier Inc. All rights reserved

Significant biophysical and genetic properties of maize inbred lines and hybrids with erect top leaves

This study confirms the hypothesis that there are elite maize inbred lines and hybrids with erect top leaves, which have a dominant property of an efficient photosynthetic and fluorescent model that is successfully used in modern breeding programmes and the production hybrid seed and commercial maize. This statement is supported by the displayed results on the erect top leaves, the dynamics of grain dry-down during the maturation period and photosynthetic and florescence parameters: the temperature dependence of the delayed chlorophyll fluorescence intensity, the Arrhenius criterion for the determination of critical temperatures (phase transition temperatures) and the activation energies. The presented results show that properties of observed maize inbreds and their hybrids are based on the nature of conformational and functional changes that occur in their thylakoid membranes and other chemical tissues structures of grain and intact leaves, as well as, on positive effects in maize breeding. Moreover, other relevant significant breeding and seed production properties (commercial maize quality over grain structure, physical and chemical parameters) of maize inbred lines and their hybrids were analyzed in the present study