Modeling dynamic states of the hypothalamic-pituitary-adrenal system and cortisol concentration

Hipotalamo-hipofizno-adrenalna (eng. hypothalamic-pituitary-adrenal, HPA) osa predstavlja složen neuroendokrini sistem koji učestvuje u održavanju optimalnog dinamičkog stanja živog sistema (homeostaze). Bilo da je u osnovnom (bazalnom) ili nekom pobuđenom stanju pod dejstvom stresa, takav složeni nelinearni sistem je uvek daleko od termodinamičke ravnoteže i poseduje povratnu spregu. Zato hormone koji ga čine nalazimo u različitim dinamičkim stanjima. U osnovnom stanju, tzv. bazalnoj fiziologiji, koncentracija hormona kortizola, krajnjeg produkta i glavnog efektornog hormona HPA sistema čoveka, ispoljava složenu oscilatornu evoluciju u vremenu, sa unutardnevnim (ultradijalnim) oscilacijama superponiranim na dnevne (cirkadijalne) oscilacije. Na osnovu sve većeg broja dokaza postalo je očigledno da je odgovarajuća oscilatorna dinamika HPA sistema nepohodan preduslov za normalno funkcionosanje i zdravlje organizma, s obzirom na to da su promene u dinamičkom ponašanju HPA sistema povezane sa mnogim metaboličkim i psihijatrijskim poremećajima. Stoga je potrebno sveobuhvatnije ispitivanje dinamičkih svojstava HPA ose, koje obuhvata ne samo eksperimentalne studije, već i modeliranje i predviđanje na bazi numeričkih simulacija. U tom cilju je u skorije vreme razvijen priličan broj matematičkih modela koji mogu da simuliraju različite dinamičke karakteristike HPA ose u njenim osnovnim kao i u patološkim stanjima. Modeliranje mehanizma procesa na bazi stehiometrijskih relacija između reakcionih vrsta, i osnovnih principa nelinerane dinamike se pokazalo kao koristan pristup u simuliranju različitih složenih dinamičkih stanja koji se javljaju u mnogim sistemima, uključujući oscilatorno ponašanje HPA sistema. Glavni cilj ove doktorske disertacije je modeliranje dinamičkih stanja HPA sistema čoveka i koncentracije kortizola kao reprezentativnog hormona za prikazivanje tih stanja, koja se mogu javiti pod različitim fiziološkim uslovima ili usled delovanja perturbatora HPA sistema, kao što su akutni i hronični stres. Taj cilj je postignut upotrebom stehiometrijskog modela aktivnosti HPA ose, formulisanog od strane Jelić i saradnika (2005) kao polazne osnove. U ovoj tezi, navedeni model je postepeno razvijan unapređivanjem i usklađivanjem njegovog mehanizma sa poznatim in vivo eksperimentalnim podacima. U toku istraživanja je pokazano da ovakvo modeliranje na bazi stehiometrijskih relacija između vrsta poseduje značajan potencijal za proučavanje kompleksnih nelinearnih reakcionih procesa koji se nalaze u stanjima udaljenim od termodinamičke ravnoteže, kao što su procesi koji se odigravaju u neuroendokrinom HPA sistemu...Hypothalamic-pituitary-adrenal (HPA) axis represents a complex neuroendocrine system involved in maintaining optimal dynamic state of the organism as a whole (i.e. the state of homeostasis). Whether being in its basal state or in some of the perturbed stress states, this highly nonlinear system always functions under conditions far away from the thermodynamic equilibrium, possessing various feedback mechanisms. Consequently, hormones comprising the HPA axis can be found in different dynamic states. Under basal conditions, i.e. basal physiology, concentration of a hormone cortisol, the end-product and chief effector of human HPA axis, displays complex oscillatory time-evolution, with ultradian oscillations being superimposed on circadian oscillations. It has become evident from a growing body of evidence that adequate oscillatory dynamics of HPA axis is a necessary prerequisite for its normal functioning and health, given that alterations of HPA axis dynamics are associated with many metabolic and psychiatric disorders. Thus, more exhaustive understanding of dynamic properties of HPA axis is required, accounting for not only experimental studies but also modeling and numerical simulation predictions. To this end, many mathematical models emulating different dynamical properties of HPA axis, in its regular as well as in pathological states, have been recently developed. Modeling the mechanism of a process by employing jointly stoichiometric relations between the reaction species and basic principles of nonlinear dynamics has proven to constitute a useful approach in emulating various forms of complex dynamic states occurring in a variety of systems, including the oscillatory behavior within the HPA axis. The main goal of this dissertation is the modeling of dynamical states of human HPA axis and concentration of cortisol, as a representative hormone for describing these HPA axis states, occurring under different physiological conditions or due to the impact of the HPA axis perturbators, such as acute and chronic stress. This goal was accomplished by utilizing a stoichiometric model of HPA axis activity proposed by Jelić et al. (2005) as a starting ground. In this dissertation, the above-mentioned model was gradually developed by upgrading and adjusting its mechanism with known in vivo experimental data. During the course of these investigations, it was shown how predictive modeling based on stoichiometric relations between the model’s species possessed a strong potential for studying complex nonlinear reaction processes operating in states far from thermodynamic equilibrium, such as those appearing within the neuroendocrine HPA system..

Influence of mechanical activation on microstructure and crystal structure of sintered MgO-TiO2 system

Mixtures of MgO-TiO2 were mechanically activated using high-energy planetary ball mill during 5, 10, 20, 40, 80 and 120 minutes. Sintering process was preformed in air at 1100°-1400°C for 2h. The decrease in powder's particle size was noticed as the time of mechanical activation increased and confirmed by particle size analyzer. XRD analyses were performed in order to acquire the information about phase composition. Different ratio mixtures of MgTiO3 and Mg2TiO4 are present within all sintered samples. The effect of tribophysical activation on microstructure was investigated by scanning electron microscopy. The differential thermal gravimetric analysis has been performed in order to investigate thermal behaviour of the mixtures.Smeše MgO-TiO2 su mehanički aktivirane u visoko-energetskom planetarnom mlinu tokom 5, 10, 20, 40, 80 i 120 minuta. Fazni sastav je određen rendgenskom difrakcijom. Sa porastom vremena mlevenja, primećeno je smanjenje veličine čestica praha. Takođe, ispitan je i efekat tribofizičke aktivacije na mikrostrukturu praha metodom skenirajuće elektronske mikroskopije. Radi ispitivanja termičkih svojstava praha, urađena je diferencijalna termijska analiza. Proces sinterovanja izveden je u vazduhu u temperaturnom opsegu od 1100°-1400°C tokom 2 sata. U svim sinterovanim uzorcima uočeno je prisustvo dve faze MgTiO3 i Mg2TiO4 ali njihov međusobni odnos koncentracija varira u odnosu na temperaturu sinterovanja

Reduction in Pathogenic Biofilms by the Photoactive Composite of Bacterial Cellulose and Nanochitosan Dots under Blue and Green Light

In this study, nanochitosan dots (ChiDs) were synthesized using gamma rays and encapsulated in bacterial cellulose (BC) polymer matrix for antibiofilm potential in photodynamic therapy. The composites were analyzed for structural changes using SEM, AFM, FTIR, XRD, EPR, and porosity measurements. Additionally, ChiD release was assessed. The results showed that the chemical composition remained unaltered, but ChiD agglomerates embedded in BC changed shape (1.5–2.5 µm). Bacterial cellulose fibers became deformed and interconnected, with increased surface roughness and porosity and decreased crystallinity. No singlet oxygen formation was observed, and the total amount of released ChiD was up to 16.10%. Antibiofilm activity was higher under green light, with reductions ranging from 48 to 57% under blue light and 78 to 85% under green light. Methicillin-resistant Staphylococcus aureus was the most sensitive strain. The new photoactive composite hydrogels show promising potential for combating biofilm-related infections

Diffraction pattern of the light on track in track detectors

U ovom radu razvijen je model i programski kod za formiranje difrackione slike svetlosti, koja prolazi kroz tragove u čvrstim trag detektorima. Prostiranje svetlostnog talasa, koji prolazi kroz trag, modelovan je na osnovu Hajgens-Frenolovog principa. Napisan je programski kod da se ispita promena difrackione slike svetlosti u zavisnosti od promene parametara traga. Cilj rada je da se na osnovu difrackione slike traga odrede parametri traga čestice u trag detektorima.The model and program code for creation of diffraction pattern of the light, when passes through track in solid state track detectors were developed in the paper. Wave-light was modelled according to Huygens-Fresnel principle. The program code was developed for correlation of diffraction pattern and track parameters. The developed model can be applied for analysis of tracks in track detectors.Зборник радова : XXIX симпозијум ДЗЗСЦГ : Сребрно језеро, 27-29. септембар 2017. годин

Diffraction pattern of the light on track in track detectors

U ovom radu razvijen je model i programski kod za formiranje difrackione slike svetlosti, koja prolazi kroz tragove u čvrstim trag detektorima. Prostiranje svetlostnog talasa, koji prolazi kroz trag, modelovan je na osnovu Hajgens-Frenolovog principa. Napisan je programski kod da se ispita promena difrackione slike svetlosti u zavisnosti od promene parametara traga. Cilj rada je da se na osnovu difrackione slike traga odrede parametri traga čestice u trag detektorima.The model and program code for creation of diffraction pattern of the light, when passes through track in solid state track detectors were developed in the paper. Wave-light was modelled according to Huygens-Fresnel principle. The program code was developed for correlation of diffraction pattern and track parameters. The developed model can be applied for analysis of tracks in track detectors.Зборник радова : XXIX симпозијум ДЗЗСЦГ : Сребрно језеро, 27-29. септембар 2017. годин

Characterization of glycidyl methacrylate based magnetic nanocomposites

Magnetic and non-magnetic macroporous crosslinked copolymers of glycidyl methacrylate and trimethylolpropane trimethacrylate were prepared by suspension copolymerization and functionalized with diethylenetriamine. The samples were characterized by mercury porosimetry, scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), Fourier transform infrared spectroscopy analysis (FTIR-ATR), thermogravimetric analysis (TGA), X-ray diffractometry (XRD), atomic force microscopy (AFM), transmission electron microscopy (TEM) and SQUID magnetometry. The FTIR-ATR analysis of synthesized magnetic nanocomposites confirmed the presence of magnetite and successful aminofunctionalization. Non-functionalized and amino-functionalized nanocomposites exhibited superparamagnetic behavior at 300 K, with a saturation magnetization of 5.0 emu/g and 2.9 emu/g, respectively. TEM analysis of the magnetic nanocomposite has shown that magnetic nanoparticles were homogeneously dispersed in the polymer matrix. It was demonstrated that incorporation of magnetic nanoparticles enhanced the thermal stability of the magnetic nanocomposite in comparison to the initial non-magnetic macroporous copolymer

Supplementary material for the article: Lončarević, B.; Lješević, M.; Marković, M.; Anđelković, I.; Gojgić-Cvijović, G.; Jakovljević, D.; Beškoski, V. Microbial Levan and Pullulan as Potential Protective Agents for Reducing Adverse Effects of Copper on Daphnia Magna and Vibrio Fischeri. Ecotoxicology and Environmental Safety 2019, 181, 187–193. https://doi.org/10.1016/j.ecoenv.2019.06.002

Supplementary material for: [https://www.sciencedirect.com/science/article/pii/S014765131930630X?via%3Dihub]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3158

Antibacterial potential of electrochemically exfoliated graphene sheets

Electrochemically exfoliated graphene is functionalized graphene with potential application in biomedicine. Two most relevant biological features of this material are its electrical conductivity and excellent water dispersibility. In this study we have tried to establish the correlation between graphene structure and its antibacterial properties. The exfoliation process was performed in a two electrode-highly oriented pyrolytic graphite electrochemical cell. Solution of ammonium persulfate was used as an electrolyte. Exfoliated graphene sheets were dispersed in aqueous media and characterized by atomic force microscopy, scanning electron microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, X photoelectron spectroscopy, X-ray diffraction, electron paramagnetic resonance, zeta potential, contact angle measurements and surface energy. Antibacterial assays have shown lack of the significant antibacterial activity. Major effect on bacteria was slight change of bacteria morphology. Membrane remained intact despite significant change of chemical content of membrane components.This is the peer reviewed version of the paper: Marković, Z. M., Matijašević, D. M., Pavlović, V. B., Jovanović, S. P., Holclajtner-Antunović, I. D., Špitalský, Z., Mičušik, M., Dramićanin, M. D., Milivojević, D. D., Nikšić, M. P., & Todorović Marković, B. M. (2017). Antibacterial potential of electrochemically exfoliated graphene sheets. Journal of Colloid and Interface Science, 500, 30–43. [https://doi.org/10.1016/j.jcis.2017.03.110][https://www.sciencedirect.com/science/article/abs/pii/S0021979717303776?via%3Dihub

Supplementary data for article: Kekez, B. D.; Gojgic-Cvijovic, G. D.; Jakovljevic, D. M.; Stefanovic Kojic, J. R.; Markovic, M. D.; Beskoski, V. P.; Vrvic, M. M. High Levan Production by Bacillus Licheniformis NS032 Using Ammonium Chloride as the Sole Nitrogen Source. Applied Biochemistry and Biotechnology 2015, 175 (6), 3068–3083. https://doi.org/10.1007/s12010-015-1475-8

Supplementary material for: [https://doi.org/10.1007/s12010-015-1475-8]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1670

The Effects of Microbial Polysaccharides on the Copper Accumulation in Daphnia magna

Copper is one of the leading metal pollutants in the water, which can cause adverse effects when present in high concentrations. The Daphnia magna is a model organism usually used for the determination of ecotoxicological effects of various compounds since it is highly sensitive to toxic compounds [1]. The aim of this work was to investigate the potential application of microbial extracellular polysaccharides (EPS), levan and pullulan, as agents for reducing the copper toxicity to D. magna. The protective effects of EPS were estimated based on the accumulation of copper in the D. magna cells. Levan is a branched fructane EPS [2] and the one used in this study was produced by Bacillus licheniformis NS032. Pullulan, a linear glucan EPS [3], was produced by Aureobasidium pullulans CH-1. The D. magna were exposed to 50 µg/dm3 of Cu (II) or a combination with 50 mg/dm3 and 100 mg/dm3 of levan or pullulan for 48h in the acute test. Additionally, the prolonged test was performed, where the daphnia were exposed to a 10 µg/dm3 of Cu (II) with or without 50 mg/ dm3 of levan or pullulan for 5 days. After the exposure period, the samples were digested and the accumulation of copper in D. magna was analysed using the iCAP Qc ICP-MS (Thermo Scientific, United Kingdom). The results showed that animals exposed to Cu (II) only, accumulated Cu (II) in a greater amount after the prolonged test compared to the acute one, despite the lower concentration. The treatment with EPS during the acute test increased the copper accumulation for both EPS concentrations tested, whereas during the prolonged exposure test, the Cu (II) accumulation was inhibited. Considering that protective effects of levan and pullulan were observed only with lower copper concentrations and 5 days of exposure, additional experiments are necessary to determine the mechanism of EPS action in order to confirm their possible use as protective agents