Dejan Godjevac

Relevance of the ability of fructose 1,6-bis(phosphate) to sequester ferrous but not ferric ions

The cytoprotective activity of F16BP has been documented in severe conditions such as convulsions, reperfusion injury, septic shock, diabetic complications, hypothermia-induced injury, UV-provoked skin damage and in other processes including apoptosis and excitotoxicity. F16BP shows very efficient cytoprotective activity in astroglial cells exposed to H(2)O(2)-provoked oxidative stress and during neuronal injury caused by hypoxic conditions. As most of the aforementioned processes involve iron activity-related conditions, we investigated the ferric and ferrous iron binding properties of F16BP under physiological conditions using (31)P NMR and EPR spectroscopy. Our results indicate that cytoprotective F16BP activity is predominantly based on ferrous iron sequestration. (31)P NMR spectroscopy of F16BP employing paramagnetic properties of iron clearly showed that F16BP forms stabile complexes with Fe(2+) which was verified by EPR of another divalent cation-Mn(2+). On the other hand, F16BP does not sequester ferric iron nor does it increase its redox activity as shown by (31)P NMR and EPR spin-trapping. Therefore, F16BP may be beneficial in neurodegenerative and other conditions that are characterised by ferric iron stores and deposits.

Influence of the chemical structure of poly(urea-urethane-siloxane)s on their morphological, surface and thermal properties

Segmented poly(urethane-urea-siloxane)s (PUUS) were synthesized using 4,4′-methylenediphenyl diisocyanate (MDI) and ethylene diamine (ED) as the hard segment components and hydroxypropyl-terminated poly(dimethylsiloxane) (PDMS) as the soft segment component, where the hard segment content ranged from 38 to 65 wt%. Segmented PUUSs were prepared by a two-step polymerization procedure in tetrahydrofuran/N-methylpyrrolidone (THF/NMP) mixture with a large proportion of polar solvent. The structure, composition and hard segment length were determined by 13C NMR and two-dimensional correlation spectroscopy. Thermal, mechanical, small-angle X-ray scattering and hydrogen bonding analyses indicated the formation of the microphase-separated copolymers with high tensile strength. Globular superstructures observed in the copolymer films by scanning electron microscopy (SEM) and atomic force microscopy (AFM) were probably arisen from the microstructural organization of the MDI-ED segments, depending on their content and length. The PUUS copolymers showed high water resistance and became more hydrophobic with increasing weight fraction of PDMS.

Comparative analysis of parthenolide content in Tanacetum larvatum, an endemic species of Montenegro, collected from three different locations

Plants from the genus Tanacetum L. (Asteraceae) have been used in traditional medicine from ancient times, of which Tanacetum parthenium (L.) Shultz-Bip. (feverfew) has been known as a remedy for the treatment of various diseases, including migraine, arthritis, fever, vertigo, menstrual disorders, stomach-ache, and psoriasis [1]. Additionally, T. vulgare L. (common tansy) and T. microphyllum DC. are useful in the treatment of various inflammatory disorders [2, 3]. Recent investigation of T. larvatum extract suggested the application of this species as an alternative or supplementary herbal remedy for the treatment of inflammatory diseases due to its anti-inflammatory and anti-ulcer activities [4]. The secondary metabolites that mediate these pharmacological effects are mainly biologically active sesquiterpene lactones, such as parthenolide and hydroxyachillin. Parthenolide, found in significant amounts in feverfew, has been indirectly linked to the anti-migraine action of feverfew preparations [5], as well as to anti-tumor and anti-inflammatory properties [6, 7]. The mode of parthenolide activity comprises the inhibition of prostaglandin production [8] and 5-hydroxytryptamine secretion [9] as mediators of inflammation. Besides, parthenolide was shown to suppress phorbol-induced mouse ear and carrageenan-induced rat paw edema, inhibiting the platelet activation [10, 11] and impairing the activity of the transcriptional factor NF-kB [12, 13]. Herrera et al. reported a strong intracellular antioxidant activity of this sesquiterpene lactone in hippocampal HT22 cells [14]. As Miglietta et al. showed that parthenolide exerted in vitro stimulatory activity on tubulin assembly, the tubulin/microtubule system may represent a novel molecular target to be utilized in developing new combinational anticancer strategies [15]. Recent investigation, confirmed its gastric anti-ulcer properties due to its ability to restore the reduction of sulfhydryl groups within the gastric mucosa and to increase mucosal PGE2 level [3, 16]. Feverfew from Serbia, as previously reported, does not contain parthenolide [17]. Because of the assumed importance of parthenolide content for pharmacological activities, supported by the studies already performed, we investigated the variation of parthenolide content in T. larvatum (Gris.) Kanitz. from Montenegro [18, 19], during a five-year period. Collected materials from three different locations were subjected to quantitative 1H NMR and HPLC analysis in order to get more insight whether the parthenolide content in the T. larvatum aerial parts is a stable property during five years period of investigation. We also measured the reduction of DPPH absorption by investigated T. larvatum extracts to indicate the capacity of the extracts to scavenge free radicals, independent of any enzymatic activity. Quantitative 1H NMR and HPLC analysis revealed the parthenolide content (Table 1) in the aerial parts of T. larvatum, collected during the phase of flowering at three natural habitats in Montenegro, Komovi Mountain (Sample a), Prokletije Mountain (Samples b), and Sinjajevina Mountain (Sample c), in the period of 2001–2005. Concerning that the amount of parthenolide might decrease during storage, the quantitative analysis was performed immediately after collection and drying of the plant material. The parthenolide level ranged from 0.40 to 1.93%, and the presented results were in accordance with reported data [20]. Although variations in the percentage were registered, the parthenolide content in all samples was comparable to that found in feverfew. Moreover, it is evident that the parthenolide amount varied during the investigated period, that in sample c being the most consistent.