Showing papers by "Vesna Vasić published in 2015"

Myeloperoxidase Inhibitors as Potential Drugs.

Abstract: Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily. This enzyme is physiologically expressed in circulating neutrophils, monocytes and some tissue macrophages including microglia. MPO plays an essential role in the antimicrobial and antiviral system of humans. The microbicidal activity of MPO exists due to its capability to oxidize halide and pseudohalide ions (CI(-), Br(-), I(-) and SCN(-)) by H2O2, thereby producing respective hypohalous acids (HOX). During the phagocytosis of pathogens, azurophilic granules release their content together with MPO into phagolysosomes. On the other hand, MPO can be discharged outside the phagocytes. Due to this, tissue damage during inflammation is greatly promoted by MPO-derived oxidants. Regarding its activity, MPO is a key factor in a great number of conditions within the group of cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, kidney diseases and immune-mediated diseases. Therefore, MPO and its downstream inflammatory pathways might be attractive targets for both prognostic and therapeutic intervention in the prophylaxis of all mentioned illnesses. Nowadays, structure and reaction mechanism of MPO are known, which enable rational strategy in the development of specific MPO inhibitors that still preserve MPO activity during host defense from bacteria, but hinder pathophysiologically persistent activation of MPO. Various methods for MPO activity inhibition and unfavorable effects of MPO-derived oxidants remodeling will be discussed. Emphasis will be put on various known inhibitors, as well as on newly investigated natural products, which can also inhibit MPO activity.

Spectrophotometric observations of thiacyanine dye J-aggregation on citrate capped silver nanoparticles

Abstract: Abstract The J-aggregation of anionic cyanine dye, 5,5’ – disulfopropyl-3,3’ – dichloro - thiacyanine sodium salt (TC) in the presence of 2x10-3 M KCl and citrate capped silver nanoparticles (AgNPs, diameter ~10nm) was investigated. The influence of added salt (KCl), as well as AgNPs and TC concentration on the intensity of the absorption bands with the maxima at 464 and 481 nm, characteristic of the J-aggregation of the dye in solution and on AgNPs surface, respectively, was studied. The spectrophotometric and fluorescence spectra confirmed that AgNPs induced the decomposition of J-aggregates formed in solution on the account of their formation on NPs surface. The obtained results enabled the evaluation of number of TC molecules per AgNPs participating in J-aggregate formation. The experimental results yielded about 320 molecules of TC per AgNPs in at least three layers in a slanted orientation.

Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum / Povreda Mozga Menja Ektonukleotidazne Aktivnosti I Nivo Adeninskih Nukleotida U Serumu Pacova

Abstract: Background Cortical stab injury (CSI) induces changes in the activity, expression and cellular distribution of specific ectonucleotidases at the injury site. Also, several experimentally induced neuropathologies are associated with changes in soluble ectonucleotidase activities in the plasma and serum, whilst various insults to the brain alter purine compounds levels in cerebrospinal fluid, but also in serum, indicating that insults to the brain may induce alterations in nucleotides release and rate of their hydrolysis in the vascular system. Since adenine nucleotides and adenosine regulate diverse cellular functions in the vascular system, including vascular tone, platelet aggregation and inflammatory responses of lymphocytes and macrophages, alterations of ectonucleotidase activities in the vascular system may be relevant for the clinical outcome of the primary insult. Methods We explored ectonucleotidase activities using specific enzyme assays and determined adenine nucleotides concentrations by the UPLC method in the rat serum after cortical stab injury. Results At 4-h post-injury, ATP and AMP hydrolysis increased by about 60% and 40%, respectively, while phosphodiesterase activity remained unchanged. Also, at 4-h post-injury a marked decrease in ATP concentration and more than 2-fold increase in AMP concentration were recorded. Conclusions CSI induces rapid up-regulation of nucleotide catabolizing soluble ectonucleotidases in rat serum, which leads to the observed shift in serum nucleotide levels. The results obtained imply that ectonucleotidases and adenine nucleotides participate in the communication between the brain and the vascular system in physiological and pathological conditions and thereby may be involved in the development of various human neuropathologies.