Platinum and ruthenium complexes as promising molecules in cancer therapy

Cancer is one of the most common fatal diseases in humans nowadays. About 20 million new cancer cases are expected in the next two decades worldwide. The development of new chemotherapeutic agents with improved properties is presently the main challenge in the medicinal chemistry. Cisplatin was introduced to oncology in 1978 as first chemotherapeutic agent regarding its specific interaction with DNA, leading to its damage and causing the cell death. Since the first application of cisplatin in cancer therapy, there has been a growing interest in new metal-based compounds, in particular platinum and ruthenium complexes, with better anticancer activity and less side-effects compared to cisplatin. Carboplatin and oxaliplatin have shown promising action against some types of cancer, which are resistant to cisplatin. With the aim to overcome cross-resistance to these Pt(II) drugs, bioavailable platinum complexes (satraplatin and picoplatin) firstly found application as orally administered drugs, as well as some combined therapies of Pt(II) drugs (cisplatin, picoplatin) with specific resistant modulators. In recent years, novel polymer and liposomal formulations of platinum drugs (prolindac, lipoplatin, lipoxal, aroplatin) have been designed with strategy to improve drug delivery to target cancer cells and reduce toxicity. Complexes based on ruthenium have great potential to become leading candidates for the medical use in anticancer therapy. Some of these compounds have shown good anticancer activity, both in vitro and in vivo and two of them (KP1019 and NAMI-A) have passed clinical trials and given promising results

The role of EPR spectroscopy in studies of the oxidative status of biological systems and the antioxidative properties of various compounds

In this era of intense study of free radicals and antioxidants, electron paramagnetic resonance (EPR) is arguably the best-suited technique for such research, particularly when considering biochemical and biological systems. No attempt was made to cover all the topics of EPR application but instead attention was restricted to two areas that are both novel and received less attention in previous reviews. In the first section, the application of EPR in assessing the oxidative status of various biological systems, using endogenous stabile paramagnetic species, such as the ascorbyl radical, semiquinone, melanin, and oxidized pigments, is addressed. The second section covers the use of EPR in the emerging field of antioxidant development, using EPR spin-trapping and spin-probing techniques. In both sections, in addition to giving an overview of the available literature, examples (mostly from the authors' recent work) are also presented in sufficient detail to illustrate how to explore the full potential of EPR. This review aims at encouraging biologists, chemists and pharmacologists interested in the redox metabolism of living systems, free radical chemistry or antioxidative properties of new drugs and natural products to take advantage of this technique for their investigations

O mogućnostima naučnog objašnjenja zasnovanog na metodološkom individualizmu u antropologiji

Rad se bavi primenom metodološkog individualizma u antropologiji. U radu se preispituju kritike metodološkog individualizma koje ističu da ovaj pristup nije odgovarajući za antropologiju zbog specifičnosti te discipline. Autori polaze od toga da postoje prednosti ovog epistemološkog okvira za razumevanje fenomena kojima se bavi antropologija. Ispitivanje mogućnosti naučnog objašnjenja u okviru metodološkog individualizma stavlja se u relaciju sa suprotstavljenim epistemološkim okvirom metodološkog holizma. Druga pretpostavka autora je da antropologija nije isključivo holistička nauka, jer istorija antropološke teorije pokazuje da ova nauka ima tradiciju metodološkog individualizma. Rad prikazuje ključna dostignuća antropologa koji su svoje istraživačke i teorijske nalaze definisali primenom metodološkog individualizma. Takođe se ispituju alternativni oblici naučnog objašnjenja koji slede metodološki individualizam, u radovima savremenih antropologa (Holi, Štuhlik), kao i autora iz drugih oblasti koji slede isti metodološki postupak (Budon), a čiji zaključci su relevantni za antropologiju. Zaključak rada je da metodološki individualizam ima značajno mesto u antropologiji i da postoje područja ove discipline koja mogu imati heurističku korist od epistemoloških pristupa koji slede principe metodološkog individualizma

EDUCATION AND INOVATION AS A DRIVER FOR RURAL DESTINATION DEVELOPMENT

In this paper, authors started from the hypothesis that innovations contribute to creativity and that children become more aware of in what way they can contribute to the development of rural areas. With children, play is important, and games that strengthen the imagination and encourage children to think for themselves are one of the best ways to encourage making future, strategic decisions. The challenge was to test the game “Tesla” on older school age children from 12 to 14 years old from rural areas. 138 children from five rural schools on Fruška Gora were examined. The results showed that children from rural areas, with the help of smart devices, played the game at the same level as children from any world metropolis. What’s more, through the game, the children showed awareness of the importance of the village, staying in the village and what is needed for the village to “live”

Applicability of neural networks in the estimation of brain iron content in the diagnosis of amyotrophic lateral sclerosis

Artificial Neural Networks, or simply ANN, are mathematical/computational model that are inspired by structure and functional aspects of biological neural networks. ANN, like man, learns by example. In the process of network training, network is supplied with set of data which represents examples of network’s proper behaviour. In the research we have done, neural network is created with the task to estimate the iron content in the brain of the Amyotrophic Lateral Sclerosis (ALS) patients. Network is created and trained using Neural Pattern Recognition Tool within the software package Matlab v7.10.0.499 (R2010a). Network is trained with set of data obtained from group of 50 ALS patients. Training set contains: (i) MRI signal of brain iron, (ii) EPR signal of hydroxyl radical from cerebrospinal fluid and (iii) score on ALS Functional Rating Scale (ALSFRS) for each patient individually. The results indicate that neural networks can be successfully used to predict the high content of iron in the brain, which in the perspective opens up the possibility of using this computer model as a standard tool in the diagnosis of ALS

Different models of automata with fuzzy states

In this paper we provide a general definition of automata with fuzzy stateswhich includes as its special cases automata used by Lin et al. [29], Liu and Qiu [30,31,42]and Xing et al. [56] in the study of fuzzy discrete event systems, as well as various typesof automata constructed in [14,15,18,32] for the purpose of the determinization of fuzzyautomata. We explain the relationships between these differentmodels of automata withfuzzy states and showthat every crisp-deterministic fuzzy automaton can be transformedinto a language-equivalent automaton with fuzzy states, and vice versa

Optimization of the preparation of novel polymer/clay nanocomposites

Recent advances in material technologies have resulted in the preparation of novel polymer/clay composites with improved thermal, mechanical, optoelectronic/ magnetic properties and increased biodegradability [1]. In this study, six samples of poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (PGME) nanocomposites with organically-modified montmorillonite clay Cloisite 30B® (C30B), were prepared via suspension copolymerization. In order to obtain nanocomposites with fine spherical beads of regular shape and satisfying thermal stability the optimization of the synthesis conditions was performed. Firstly, the influence of the poly(N-vinyl pyrrolidone) (PVP) quantity in the aqueous phase was varied (1, 3 and 5 wt.%) at a constant stirring rate of 250 rpm and constant clay content C30B (10 wt.%). In the second phase of the optimization of the preparation, samples with a constant composition of the composite reaction mixture (5 wt.% PVP and 10 wt.% C30B) at a stirring rate of 250, 325 and 400 rpm, were prepared. According to the obtained results, it was concluded that the optimal conditions for preparation of these composites are 5 wt.% of PVP and 400 rpm. The prepared nanocomposites were characterized with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) in air. The structure of the prepared nanocomposites was confirmed with FTIR spectroscopy. According to the obtained SEM microphotographs the fine spherical beads, with desired size and homogeneous morphology, were prepared. Furthermore, SEM analysis was also showed that clay nanoparticles are homogeneously dispersed both inside surface and cross-section area. The incorporation of C30B clay increased the thermal stability of the prepared polymer/clay nanocomposites in comparison to the pure PGME copolymer

Optimization of the preparation of novel polymer/clay nanocomposites

Recent advances in material technologies have resulted in the preparation of novel polymer/clay composites with improved thermal, mechanical, optoelectronic/ magnetic properties and increased biodegradability [1]. In this study, six samples of poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (PGME) nanocomposites with organically-modified montmorillonite clay Cloisite 30B® (C30B), were prepared via suspension copolymerization. In order to obtain nanocomposites with fine spherical beads of regular shape and satisfying thermal stability the optimization of the synthesis conditions was performed. Firstly, the influence of the poly(N-vinyl pyrrolidone) (PVP) quantity in the aqueous phase was varied (1, 3 and 5 wt.%) at a constant stirring rate of 250 rpm and constant clay content C30B (10 wt.%). In the second phase of the optimization of the preparation, samples with a constant composition of the composite reaction mixture (5 wt.% PVP and 10 wt.% C30B) at a stirring rate of 250, 325 and 400 rpm, were prepared. According to the obtained results, it was concluded that the optimal conditions for preparation of these composites are 5 wt.% of PVP and 400 rpm. The prepared nanocomposites were characterized with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) in air. The structure of the prepared nanocomposites was confirmed with FTIR spectroscopy. According to the obtained SEM microphotographs the fine spherical beads, with desired size and homogeneous morphology, were prepared. Furthermore, SEM analysis was also showed that clay nanoparticles are homogeneously dispersed both inside surface and cross-section area. The incorporation of C30B clay increased the thermal stability of the prepared polymer/clay nanocomposites in comparison to the pure PGME copolymer

Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler

The development of novel dry powders for dry powder inhalers (DPIs) requires the in vitro assessment of DPI aerodynamic performance. As a potential complementary method, in silico numerical simulations can provide additional information about the mechanisms that guide the particles and their behavior inside DPIs. The aim of this study was to apply computational fluid dynamics (CFDs) coupled with a discrete phase model (DPM) to describe the forces and particle trajectories inside the RS01® as a model DPI device. The methodology included standard fluid flow equations but also additional equations for the particle sticking mechanism, as well as particle behavior after contacting the DPI wall surface, including the particle detachment process. The results show that the coefficient of restitution between the particle and the impact surface does not have a high impact on the results, meaning that all tested combinations gave similar output efficiencies and particle behaviors. No sliding or rolling mechanisms were observed for the particle detachment process, meaning that simple bouncing off or deposition particle behavior is present inside DPIs. The developed methodology can serve as a basis for the additional understanding of the particles’ behavior inside DPIs, which is not possible using only in vitro experiments; this implies the possibility of increasing the efficiency of DPIs