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The idea of modern cremation was much more than a notion of a more hygienic, ecological and aesthetically acceptable method for the disposal of human remains. From its inception at the end of the 1...

Korišćenjem istorijskopravnog i aksiološkog metoda autor u radu razmatra i kritički ocjenjuje genezu prava zadržavanja, kao specifičnog in- stituta građanskog prava, počev od nastanka u rimskom pravu, preko srednjovi- jekovne regulative u pojedinim evropskokontinentalnim zakonodavstvima, do konačne kodifikacije u građanskim zakonicima. Predmet razmatranja u radu su klјučni segmenti ovog instituta u nekadašnjoj domaćoj regulativi, kao i u pojed- inim evropskim regulativama, sa fokusom na nekadašnjem austrijskom i francus- kom rješenju. Cilј rada je formulisanje odgovora na pitanja: koji su modeli regulati- va prava zadržavanja postojali kroz vrijeme, kako su i zašto evoluirali; kakav je bio odnos različitih zakonodavaca prema ovom institutu; i otkrivanje ratia njegovog sve šireg priznavanja. Autor ocjenjuje da je geneza evropske retencije kroz vri- jeme - put od njene izričite zabrane, preko kazuističkog priznavanja na nivou izuz-etka, pa do formulisanja opšteg pravila o retenciji građanskog i trgovačkog prava, te da ona u savremenoj fizionomiji oličava ne samo sredstvo pritiska na neured- nog dužnika, već i efikasno sredstvo namirenja, a u ulozi instrumenta zaštite pov- jerenja u pravni promet, pravičnosti (equitas) i ekvivalencije uzajamnih davanja u dužničko-povjerilačkim odnosima.

The author discusses different segments of the institute of euthanasia ("murder out of mercy"), especially the question of the justification of its legalization. The subject of the analysis are the solutions of certain European regulations that have completely or partially decriminalized euthanasia, and then the domestic one, in which there is a collision of the norms of criminal and medical law. According to the positive serbian criminal law, euthanasia is a criminal offense and a privileged form of murder, while the Law on Patients' Rights indirectly allows the so-called passive euthanasia, which is not the optimal solution, which introduces legal uncertainty. Тhe Preliminary Draft of the Civil Code of Serbia, which embodies the proposal for the future civil law of Serbia, proposes the decriminalization of euthanasia, which is a solution that needs to be commented on. The aim of the paper is a comparative analysis of domestic and foreign solutions of this controversial institute - through its concept, types (active and passive euthanasia) and critical analysis of the reasons for and against its introduction into the domestic law. The author evaluates the proposal of the Preliminary Draft as progress, with the idea that euthanasia, despite all the controversies that accompany it, represents the ultimate expression of a personal right to self-determination (subjective civil right sui generis), in both modalities, without distinction.

Fatty acid nitroalkenes (NO2-FA) are endogenously-generated products of the reaction of metabolic and inflammatory-derived nitrogen dioxide (.NO2) with unsaturated fatty acids. These species mediate signaling actions and induce adaptive responses in preclinical models of inflammatory and metabolic diseases. The nitroalkene substituent possesses an electrophilic nature, resulting in rapid and reversible reactions with biological nucleophiles such as cysteine, thus supporting post-translational modifications (PTM) of proteins having susceptible nucleophilic centers. These reactions contribute to enzyme regulation, modulation of inflammation and cell proliferation and the regulation of gene expression responses. Herein, focus is placed on the reduction-oxidation (redox) characteristics and stability of specific NO2-FA regioisomers having biological and clinical relevance; nitro-oleic acid (NO2-OA), bis-allylic nitro-linoleic acid (NO2-LA) and the conjugated diene-containing nitro-conjugated linoleic acid (NO2-cLA). Cyclic and alternating-current voltammetry and chronopotentiometry were used to the study of reduction potentials of these NO2-FA. R–NO2 reduction was observed around −0.8 V (vs. Ag/AgCl/3 M KCl) and is related to relative NO2-FA electrophilicity. This reduction process could be utilized for the evaluation of NO2-FA stability in aqueous milieu, shown herein to be pH dependent. In addition, electron paramagnetic resonance (EPR) spectroscopy was used to define the stability of the nitroalkene moiety under aqueous conditions, specifically under conditions where nitric oxide (.NO) release could be detected. The experimental data were supported by density functional theory calculations using 6–311++G (d,p) basis set and B3LYP functional. Based on experimental and computational approaches, the relative electrophilicities of these NO2-FA are NO2-cLA >> NO2-LA > NO2-OA. Micellarization and vesiculation largely define these biophysical characteristics in aqueous, nucleophile-free conditions. At concentrations below the critical micellar concentration (CMC), monomeric NO2-FA predominate, while at greater concentrations a micellar phase consisting of self-assembled lipid structures predominates. The CMC, determined by dynamic light scattering in 0.1 M phosphate buffer (pH 7.4) at 25 °C, was 6.9 (NO2-LA) 10.6 (NO2-OA) and 42.3 μM (NO2-cLA), respectively. In aggregate, this study provides new insight into the biophysical properties of NO2-FA that are important for better understanding the cell signaling and pharmacological potential of this class of mediators., Highlights • Nitro-fatty acids (NO2-FA) are electrophilic mediators of redox-regulated signaling reactions. • The relative electrophilicity of 18 carbon chain length NO2-FA is NO2-cLA » NO2-LA > NO2-OA. • Critical micellar concentrations at pH 7.4 were 10.6, 6.9 and 42.3 μM for NO2-OA, NO2-LA and NO2-cLA, respectively. • Nitrogen dioxide (.NO2) rapidly reacts with unsaturated FA and yields more stable bioactive NO2-FA byproducts.

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by cognitive decline and total brain atrophy. Despite the substantial scientific effort, the pathological mechanisms underlying neurodegeneration in AD are currently unknown. In most studies, amyloid β peptide has been considered the key pathological change in AD. However, numerous Aβ-targeting treatments have failed in clinical trials. This implies the need to shift the research focus from Aβ to other pathological features of the disease. Objective: The aim of this study was to examine the interplay between mitochondrial dysfunction, oxidative stress and blood-brain barrier (BBB) disruption in AD pathology, using a novel approach that involves the application of electron paramagnetic resonance (EPR) spectroscopy. Methods: In vivo and ex vivo EPR spectroscopy using two spin probes (aminoxyl radicals) exhibiting different cell-membrane and BBB permeability were employed to assess BBB integrity and brain tissue redox status in the 5xFAD mouse model of AD. In vivo spin probe reduction decay was analyzed using a two-compartment pharmacokinetic model. Furthermore, 15 K EPR spectroscopy was employed to investigate the brain metal content. Results: This study has revealed an altered brain redox state, BBB breakdown, as well as ROS-mediated damage to mitochondrial iron-sulfur clusters, and up-regulation of MnSOD in the 5xFAD model. Conclusion: The EPR spin probes were shown to be excellent in vivo reporters of the 5xFAD neuronal tissue redox state, as well as the BBB integrity, indicating the importance of in vivo EPR spectroscopy application in preclinical studies of neurodegenerative diseases.

Gaucher disease (GD) is a lysosomal storage disorder, caused by an impaired function of β-glucocerebrosidase, which results in accumulation of glucocerebroside in cells, and altered membrane ordering. Using electron paramagnetic resonance spin labeling, a statistically significant difference in the order parameter between the peripheral blood mononuclear cell membranes of GD patients and healthy controls was observed. Moreover, the results show that the introduction of the enzyme replacement therapy leads to the restoration of the physiological membrane fluidity. Accordingly, this simple method could serve as a preliminary test for GD diagnosis and therapy efficiency.

Albumin is the most abundant plasma protein and as such has been the subject of many studies using a variety of techniques. One of them, capable of monitoring the conformational changes and the binding capacity of proteins, is electron paramagnetic resonance spectroscopy (EPR) spin labeling. To date, albumin has been investigated using a number of different spin labels, mostly spin-labeled fatty acids (SLFAs). However, albumin can bind up to seven equivalents of fatty acids, making it difficult to determine which parts of the molecule undergo conformational changes. To obtain information from a specific site on a protein, spin labels that bind to free cysteine residues may be used. In this work, the applicability of such a label, 3-maleimido proxyl (5-MSL), was evaluated for monitoring conformational changes of bovine serum albumin (BSA) at different temperatures and pH values. Also, the effect of ethanol, reactive oxygen species (hydrogen peroxide and superoxide radical), and the binding of ligands specific for albumin, namely fatty acids, and several drugs were evaluated. The results indicate that the labeling of albumin at its free cysteine residue (Cys-34) using 5-MSL may successfully be used for the detection of conformational changes, even in the case of the subtle alterations induced by ligand binding.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the motor pathways of the central nervous system. Although a number of pathophysiological mechanisms have been described in the disease, post mortem and animal model studies indicate blood-brain barrier (BBB) disruption and elevated production of reactive oxygen species as major contributors to disease pathology. In this study, the BBB permeability and the brain tissue redox status of the SOD1 G93A ALS rat model in the presymptomatic (preALS) and symptomatic (ALS) stages of the disease were investigated by in vivo EPR spectroscopy using three aminoxyl radicals with different cell membrane and BBB permeabilities, Tempol, 3-carbamoyl proxyl (3CP), and 3-carboxy proxyl (3CxP). Additionally, the redox status of the two brain regions previously implicated in disease pathology, brainstem and hippocampus, was investigated by spectrophotometric biochemical assays. The EPR results indicated that among the three spin probes, 3CP is the most suitable for reporting the intracellular redox status changes, as Tempol was reduced in vivo within minutes (t 1/2 =2.0±0.5 min), thus preventing reliable kinetic modeling, whereas 3CxP reduction kinetics gave divergent conclusions, most probably due to its membrane impermeability. It was observed that the reduction kinetics of 3CP in vivo, in the head of preALS and ALS SOD1 G93A rats was altered compared to the controls. Pharmacokinetic modeling of 3CP reduction in vivo, revealed elevated tissue distribution and tissue reduction rate constants indicating an altered brain tissue redox status, and possibly BBB disruption in these animals. The preALS and ALS brain tissue homogenates also showed increased nitrilation, superoxide production, lipid peroxidation and manganese superoxide dismutase activity, and a decreased copper-zinc superoxide dismutase activity. The present study highlights in vivo EPR spectroscopy as a reliable tool for the investigation of changes in BBB permeability and for the unprecedented in vivo monitoring of the brain tissue redox status, as early markers of ALS.

Los murales en los templos cristianos ortodoxos siempre han tenido el siguiente objetivo: visualizar el orden litúrgico y completar la experiencia religiosa del tiempo yespacio sagrados. Fuera de los templos y oficios religiosos, los creyentes podían mantenerel contacto con estas historias santificadas y sus santos, a través del uso de los iconos quehan sido una parte inseparable de la vida cristiana siempre después del período de laiconoclasia. En la época comunista, los grandes éxitos del arte del cristianismo ortodoxose observaban fuera del contexto religioso estricto. El cambio de actitud hacia las artesvisuales influyó en su comercialización que, en gran medida, descuidó los dogmas originarios en los que este tipo de arte estaba basado. Un hecho interesante es que la propiaIglesia Ortodoxa Serbia contribuyó de manera importante a este proceso comercializandoproductos de arte ortodoxo.Este trabajo se centrará entorno a un caso específico –el caso del Ángel Blanco– un fresco mundialmente famoso, del monasterio Mileševa (sudoeste de Serbia). En las últimasdécadas esta composición ha pasado por serias “reinterpretaciones” en las que su temaprincipal –mostrar la tumba de Cristo vacía después de Su resurrección– ha sido marginalizado por haber destacado la figura del ángel blanco, a través de la reproducción sólode una parte de la composición.Este caso presenta un testimonio de varios niveles de los actuales procesos sociales y culturales en Serbia: da testimonio acerca de un largo proceso transicional que frecuentementesuponía invenciones y falsificaciones de las tradiciones nacionales y religiosas, testifica,asimismo, sobre las formas especiales de la llamada nueva religiosidad, que es consideradoa la vez tanto un fenómeno local como global, y por último, pero no menos importante,testifica sobre la secularización de las prácticas y fe ortodoxas.

Nitro-fatty acids modulate inflammatory and metabolic stress responses, thus displaying potential as new drug candidates. Herein, we evaluate the redox behavior of nitro-oleic acid (NO2-OA) and its ability to bind to the fatty acid transporter human serum albumin (HSA). The nitro group of NO2-OA underwent electrochemical reduction at −0.75 V at pH 7.4 in an aqueous milieu. Based on observations of the R–NO2 reduction process, the stability and reactivity of NO2-OA was measured in comparison to oleic acid (OA) as the negative control. These electrochemically-based results were reinforced by computational quantum mechanical modeling. DFT calculations indicated that both the C9-NO2 and C10-NO2 positional isomers of NO2-OA occurred in two conformers with different internal angles (69° and 110°) between the methyl- and carboxylate termini. Both NO2-OA positional isomers have LUMO energies of around −0.7 eV, affirming the electrophilic properties of fatty acid nitroalkenes. In addition, the binding of NO2-OA and OA with HSA revealed a molar ratio of ~7:1 [NO2-OA]:[HSA]. These binding experiments were performed using both an electrocatalytic approach and electron paramagnetic resonance (EPR) spectroscopy using 16-doxyl stearic acid. Using a Fe(DTCS)2 spin-trap, EPR studies also showed that the release of the nitro moiety of NO2-OA resulted in the formation of nitric oxide radical. Finally, the interaction of NO2-OA with HSA was monitored via Tyr and Trp residue electro-oxidation. The results indicate that not only non-covalent binding but also NO2-OA-HSA adduction mechanisms should be taken into consideration. This study of the redox properties of NO2-OA is applicable to the characterization of other electrophilic mediators of biological and pharmacological relevance. Keywords: Electrophiles, Nitrated fatty acids, Oleic acid, NO, Proteins, Serum albumin binding

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed., Graphical abstract fx1, Highlights • RONS are chemical mediators and a communication tool. • RONS and disturbed redox balance play a role in a broad range of diseases and aging. • Bacteria and toxins are important stimulators of cellular RONS formation. • Drugs should preserve beneficial redox signaling and inhibit detrimental RONS sources. • Redox drugs may target the origin, identity, location and time of RONS formation.

Anhydrobiosis is an adaptive strategy that allows withstanding almost complete body water loss. It has been developed independently by many organisms belonging to different evolutionary lines, including tardigrades. The loss of water during anhydrobiotic processes leads to oxidative stress. To date, the metabolism of free radicals in tardigrades remained unclear. We present a method for in vivo monitoring of free radical production in tardigrades, based on electron paramagnetic resonance and spin-trap DEPMPO, which provides simultaneous identification of various spin adducts (i.e., different types of free radicals). The spin trap can be easily absorbed in animals, and tardigrades stay alive during the measurements and during 24-h monitoring after the treatment. The results show that hydrated specimens of the tardigrade Paramacrobiotus richtersi produce the pure superoxide anion radical ((•)O2(-)). This is an unexpected result, as all previously examined animals and plants produce both superoxide anion radical and hydroxyl radical ((•)OH) or exclusively hydroxyl radical.

Powerful and dynamic changes are present in all spheres of society, both at national and at the global level. Those changes are very difficult to monitor due to intensive frequency of change. The changes are also present in trade. This work analyzed changes that are coming from the global environment, that intensely affect the development of modern trade. The question is whether modern trade can handle strikes coming from the global development. Large industries, commercial and financial organizations and national economies increasingly connect and turn into mutually conditional and interdependent. Greater trade integration is evident, in every year increased trade results in a higher share of exports and imports in GDP. This work also emphasizes on business performances of trade in Serbia. Results of research show that business performances of trade are still weak, though recently improved marginally. Developments in the field of trade and the change of perception of trade itself drastically improved. Despite of some improvements of business performances, modern trading and market structure relatively slowly develops and it is certain that Serbian trade still largely lagging behind comparing the trade of the European Union.

Cytochrome c (cyt c) is one of the most studied conjugated proteins due to its electron-transfer properties and ability to regulate the processes involved in homeostasis or apoptosis. Here we report an electrochemical strategy for investigating the electroactivity of cyt c and its analogs with a disrupted heme moiety, i.e. apocytochrome c (acyt c) and porphyrin cytochrome c (pcyt c). The electrochemical data are supplemented with low-temperature and spin-probe electron paramagnetic resonance (EPR) spectroscopy. The main contribution of this report is a complex evaluation of cyt c reduction and oxidation at the level of surface-localized amino acid residues and the heme moiety in a single electrochemical scan. The electrochemical pattern of cyt c is substantially different to both analogs acyt c and pcyt c, which could be applicable in further studies on the redox properties and structural stability of cytochromes and other hemeproteins.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the motor pathways of the central nervous system. Although a number of pathophysiological mechanisms have been described in the disease, post mortem and animal model studies indicate blood-brain barrier (BBB) disruption and elevated production of reactive oxygen species as major contributors to disease pathology. In this study, the BBB permeability and the brain tissue redox status of the SOD1

The binding of spin-labeled fatty acids (SLFAs) to the human serum albumin (HSA) examined by electron paramagnetic resonance (EPR) spectroscopy was studied to evaluate the potential of the HSA/SLFA/EPR technique as a biomarking tool for cancer. A comparative study was performed on two spin labels with nitroxide groups attached at opposite ends of the fatty acid (FA) chain, 5-doxyl stearic (5-DS) and 16-doxyl stearic (16-DS) acid. The effects of incubation time, different [SLFA]/[HSA] molar ratios, ethanol, and temperature showed that the position of the nitroxide group produces certain differences in binding between the two SLFAs. Spectra for different [SLFA]/[HSA] molar ratios were decomposed into two spectral components, which correspond to the weakly and strongly bound SLFAs. The reduction of SLFA with ascorbate showed the existence of a two component process, fast and slow, confirming the decomposition results. Warfarin has no effect on the binding of the two SLFAs, whereas ibuprofen significantly decreases the binding of 5-DS and has no effect on 16-DS. Together, the results of this study indicate that both SLFAs, 5-DS and 16-DS, should be used for the study of HSA conformational changes in blood induced by various medical conditions.

The issue of the work is an analysis of characteristics of land debt, known as non-accessory real right securing claims in German and Swiss law. Using the method of comparative analysis of the characteristics of this property right, author determines the similarities and differences of land debt in relation to similar types of rights, in particular in relation to a mortgage, as most similar security right, from the group of liens. Since the Draft Code of ownership and other property real rights in Serbia in 2006. proposed the introduction of real debt in Serbian law, the author of the paper examines the advantages and disadvantages of this concept in order to evaluate this assessment.. As an essential difference to the lien, the author defines the non-accessory character of land debt and multifunctional purpose. The author advocates the introduction of institute of land debt in future Serbian law, as the original non-accessory real security right (sui generis) that represents functional addittion to accessory mortgage.

Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine. (C) 2015 Elsevier Ireland Ltd. All rights reserved. Ministry of Education, Science and Technology of the Republic of Serbia {[}III45012, III41031, III41005, III45005-4]

Aim To elucidate whether Raman spectroscopy aided by extensive spectral database and neural network analysis can be a fast and confident biomarking tool for the diagnosis of various types of cancer. Methods Study included 27 patients with 11 different malignant tumors. Using Raman microscopy (RM) a total of 540 Raman spectra were recorded from histology specimens of both tumors and surrounding healthy tissues. Spectra were analyzed using the principal component analysis (PCA) and results, along with histopathology data, were used to train the neural network (NN) learning algorithm. Independent sets of spectra were used to test the accuracy of PCA/NN tissue classification. Results The confident tumor identification for the purpose of medical diagnosis has to be performed by taking into account the whole spectral shape, and not only particular spectral bands. The use of PCA/NN analysis showed overall sensitivity of 96% with 4% false negative tumor classification. The specificity of distinguishing tumor types was 80%. These results are comparable to previously published data where tumors of only one tissue type were examined and can be regarded satisfactorily for a relatively small database of Raman spectra used here. Conclusion In vitro RM combined with PCA/NN is an almost fully automated method for histopathology at the level of macromolecules. Supported by an extensive tumor spectra database, it could become a customary histological analysis tool for fast and reliable diagnosis of different types of cancer in clinical settings.