Search

Vojvodina is an area with long and rich cultural tradition. The first museum in Vojvodina was founded in the 19th Serbian century by Matica Srpska, from which the present Museum of Vojvodina emerged. City museums are located in all major cities in Vojvodina, and each of them houses valuable artifacts. Museum visitation is not at a high level and it is necessary to invest a lot of effort and innovation that museums become more interesting than surfing the Internet. One of the good ways that museums become appealing to visitors is the event 'Museum Night'. Museums contribute to tourism value of certain destinations, and owing to tourism, increase the number of visitors, gain popularity and fulfill their cultural and educational function. Vojvodina je prostor sa dugom i bogatom kulturnom tradicijom. Prvi muzej u Vojvodini osnovala je Matica srpska u 19. veku iz koga je nastao današnji Vojvođanski muzej. Gradski muzeji nalaze se u svim većim gradovima u Vojvodini, i svaki od njih poseduje vredne eksponate. Posećenost muzeja nije na zavidnom nivou i potrebno je uložiti dosta truda i inovacija da muzeji postanu zanimljiviji od 'surfovanja' Internetom. Jedan od dobrih načina da muzeji postanu interesantni za posetioce jeste i manifestacija 'Noć muzeja'. Muzeji doprinose turističkoj vrednosti pojedinih mesta, a zahvaljujući turizmu povećavaju broj svojih posetilaca, stiču popularnost i ispunjavaju svoju kulturno-obrazovnu funkciju.

Bor je bilo koji četinar roda Pinus koji pripada porodici Pinaceae. U Republici Srbiji nalaze se prirodne i veštačke šume crnog bora Pinus nigra Arnold. Kora bora se vekovima koristila u tradicionalnoj medicini, međutim tek u novije vreme su otkriveni i potvrđeni njeni pozitivni biološki efekti u medicini. Najpoznatiji komercijalni preparat kore bora je piknogenol, standardizovani ekstrakt kore francuskog primorskog bora Pinus pinaster Aiton, koji raste duţ obale jugozapadne Francuske. Pozitivni efekti koje ispoljava piknogenol, kao što su antioksidativno, hipoglikemijsko, hipolipidemijsko delovanje, zasnovani su na njegovom visokom sadržaju fenolnih jedinjenja. Danas, i pored saznanja da je kora bora bogata sekundarnim metabolitima ona najčešće završava kao nusproizvod drvne industrije. Ciljevi ovog rada bili su ispitivanje kvalitativnih i kvantitativnih karakteristika i biohemijskih aktivnosti ekstrakata kore crnog bora Pinus nigra sa Mokre gore i Tare, dobijenih različitim rastvaračima; upoređivanje glikemijskog i lipidnog delovanja ekstrakta kore bora Pinus nigra sa komercijalnim preparatom piknogenol; uticaj ekstrakta kore bora Pinus nigra i piknogenola na delovanje standardnih antidijabetika metformina i gliklazida; kao i uticaj na parametre oksidativnog stresa nakon izlaganja životinja toksičnoj dozi paracetamola. In vitro ispitivanja su uključivala analizu ekstrakata dobijenih različitim rastvaračima. Ukupni sadržaj fenola, tanina, flavonoida i proantocijanidna, kao i ispitivanje antioksidativne aktivnosti kroz pet različitih metoda, određivani su spektrofotometrijski. Vršena je analiza ekstrakata kore bora visokoefikasnom tečnom hromatografijom (HPLC). In vivo ispitivanje je rađeno na 156 albino laboratorijska pacova soja Wistar. Eksperimentalne ţivotinje su tokom 7 dana per os primale ekstrakt kore crnog bora poreklom sa Mokre gore 100 mg/kg, koji je pokazao najbolju aktivnost, piknogenol 50 mg/kg, metformin 100 mg/kg, gliklazid 10 mg/kg, kao i njihove kombinacije. Za ispitivanje uticaja primenjivanih supstanci na glikemiju ţivotinja korišćeni su test oralnog podnošenja glukoze i indukcija trajne hiperglikemije aloksanom. Od biohemijskih parametara u serumu je određivana koncentracija lipida, kao i parametric pokazatelji funkcije bubrega i jetre. Ex vivo ispitivanja uključivala su određivanje intenzitet lipidne peroksidacije i anktivnosti enzima antioksidativne zaštite u homogenatu jetre ispitivanih ţivotinja, nakon primene toksične doze paracetamola. HPLC analizom ekstrakata kore crnog bora utvrđeno je da ekstrakti poreklom sa Mokre gore i Tare u najvećoj meri sadrţe taksifolin, a zatim katehin, njegove derivate, kafenu kiselinu i epikatehin. PotvrĎen je visok antioksidativni kapacitet piknogenola, ali takođe i značajan antioksidativni kapacitet ekstrakata kore crnog bora, sa najboljim rezultatima kod ekstrakta poreklom sa Mokre gore. Sedmodnevni tretman ekstraktom kore bora 100 mg/kg, metforminom 100 mg/kg, gliklazidom 10 mg/kg i piknogenolom 50 mg/kg, kod ţivotinja sa aloksanski izazvanim dijabetesom, doveo je do sniženja glikemije u krvi. Uočeno je povećanje konentracije HDL holesterola i značajno sniženje serumskih triglicerida kod dijabetičnih i normoglikemičnih ţivotinja koje su primale piknogenol, ekstrakta kore bora, gliklazid i metformin u poređenju sa kontrolnom grupom ţivotinja. Zajednička primena ekstrakta kore bora i standardnih antidijabetika značajno je snizila vrednosti AST, ALP i direktni bilirubin u grupi dijabetičnih i normoglikemičnih ţivotinja u odnosu na kontrolnu grupu, čime se ukazuje na potencijalno hepatoprotektivno delovanje ekstrakta kore crnog bora. Oštećenje jetre izazvano toksičnom dozom paracetamola je potvrđeno ispitivanim parametrima, uključujući oksidativni status u homogenatu jetre i histološka ispitivanja. Rezultati našeg istraživanja su pokazali da piknogenol 50 mg/kg, kao i ekstrakt kore crnog bora 100 mg/kg značajno smanjuju nivo MDA u poređenju sa kontrolnom grupom i grupom koja je primala paracetamol. Na osnovu rezultata istraţivanja može se zaključiti da primena piknogenola i ekstrakta kore crnog bora: ublaţava poremećaj homeostaze glukoze, utiče povoljno na lipidni status, značajno potencira antihiperglikemijsko delovanje metformina i hipoglikemijski efekat gliklazida, sprečava poremećaj biohemijskih parametara pokazatelja funkcije jetre i bubrega u serumu ispitivanih životinja i ispoljava značajno in vitro antioksidativno delovanje i sprečava oštećenje jetre laboratorijskih životinja izazvano toksičnom dozom paracetamola., A pine is any conifer in the genus Pinus of the family Pinaceae. In the Republic of Serbia there are natural and artificial forests of black pine Pinus nigra Arnold. Pine bark has been used for centuries in traditional medicine, but only recently its positive biological effects has been revealed and confirmed in medicine. The most famous commercial pine bark product is Pycnogenol, a standardized extract of the French maritime pine bark (Pinus pinaster Aiton), which grows along the coast of southwestern France. The positive effects of Pycnogenol, such as antioxidant, hypoglycemic, hypolipidemic, are based on its high content of phenolic compounds. Nowdays, despite the knowledge that the pine bark is rich in secondary metabolites, it usually ends up as a by-product of the wood industry. The objectives of this dissertation were to investigate the qualitative and quantitative characteristics and biochemical activities of the black pine (Pinus nigra) extracts from Mokra gora and Tara, obtained by different solvents; comparison of glycemic and lipid action of Pinus nigra bark extract with commercial product Pycnogenol; the influence of black pine bark extract and Pycnogenol on the action of standard antidiabetics metformin and gliclazide; as well as the influence on the parameters of oxidative stress in animals exposed to the toxic dose of paracetamol. In vitro analyses included the analysis of extracts obtained with different solvents. The total phenolic, tannin, flavonoid and proanthocyanidin content, as well as the antioxidant activity tests, were determined spectrophotometrically. High-efficiency liquid chromatography (HPLC) was performed in order to determine black pine bark extract content. In vivo analyses was performed on 156 albino Wistar laboratory rats. Experimental animals received for 7 days per os: black pine bark extract obtained from Mokra gora 100 mg/kg, which showed the best activity; Pycnogenol 50 mg/kg; metformin 100 mg/kg; gliclazide 10 mg/kg; and their combinations. An oral glucose tolerance test and the aloxan-induced hyperglycaemia were used to examined the effects of the substances on experimental animals. Biochemical parameters, the lipids concentration and parameters of the kidney and liver function, were determined in animal serum. Ex vivo analyses included determination of lipid peroxidation activity and the activity of antioxidant protection enzymes in liver homogenates of the test animals, after administration of a toxic dose of paracetamol. HPLC analysis of black pine bark extracts obtained from Mokra gora and Tara showed the greatest content of taxifolin, then catechin, and its derivatives, caffeic acid and epicatechin. A high antioxidative capacity of Pycnogenol was confirmed, but also a significant antioxidant capacity of black pine bark extract, with the best results in the extract obtained from Mokra gora. Seven-day treatment in aloxan-induced diabetes animals with 100 mg/kg black pine bark extract, metformin 100 mg/kg, gliclazide 10 mg/kg and Pycnogenol 50 mg/kg led to a decrease of serum glycemic index. There was an increase in the HDL cholesterol concentration and a significant reduction in serum triglycerides in diabetic and normoglycemic animals which received Pycnogenol, black pine bark extract, gliclazide and metformin compared to the control group. Concomitant usage of the black pine bark extract and standard antidiabetics significantly reduced the levels of AST, ALP and direct bilirubin in the group of diabetic and normoglycemic animals compared to the control group, indicating the potential hepatoprotective action of the black pine bark extract. Damage to the liver caused by the toxic dose of paracetamol was confirmed by the liver homogenate oxidative status and histological examination. The results of our study have shown that Pycnogenol 50 mg/kg, as well as 100 mg/kg black pine bark extract significantly reduce the level of MDA in comparison with the control and the paracetamol treated group. Based on the results of the dissertation, it can be concluded that the use of Pycnogenol and black pine bark extract alleviate glucose homeostasis disorder; positively affects the lipid status; significantly increases the antihyperglycemic effect of metformin and the hypoglycemic effect of gliclazide; prevents impairment biochemical parameters of the liver and kidney function in the serum of the experimental animals; significantly exhibits in vitro antioxidant activity and prevents liver damage caused by toxic dose of paracetamol in experimental animals.

In states of intestinal dysbiosis, a perturbation of the normal microbiome composition, the intestinal epithelial barrier (IEB) permeability is increased as a result of the disruption of the epithelial tight junction protein network, in which occludin is mostly affected. The loss of IEB integrity promotes endotoxemia, that is, bacterial lipopolysaccharide (LPS) translocation from the intestinal lumen to the circulatory system. This condition induces an enhancement of pro-inflammatory cytokines, which leads to neuroinflammation through the gut-brain axis. Orexin-A (OX-A), a neuropeptide implicated in many physiological functions and produced mainly in the brain lateral hypothalamic area, is expressed also in several peripheral tissues. Orexin-producing neurons have been found in the myenteric plexus to project to orexin receptor 1 (OX-1R)-expressing enterocytes of the intestinal villi. In the present study we investigated the protective role of OX-A against LPS-induced increase of IEB permeability and microglia activation in both an in vivo and in vitro model of the gut-brain axis. By exploiting biochemical, immunocytochemical, immunohistochemical, and functional approaches, we demonstrate that OX-A preserves the IEB and occludin expression, thus preventing endotoxemia and subsequent neuroinflammation.

Uloga micela u razvoju farmaceutskih oblika zasniva se na njihovom potencijalu da kao transportni sistemi povećaju bioraspoloživost lekovite supstance i unaprede njen farmakokinetski profil. Micele mogu da modifikuju propustljivost biološkuh membrana, omoguće kontrolisano oslobađanje lekovite supstance iz farmaceutskog oblika, stabilizuju lekovitu supstancu, itd. Kombinovanje različitih surfaktanata kao gradivih jedinica omogućava konstruisanje micela sa poželjnim fizičko-hemijskim karakteristikama. Takođe, mešovite micele između čijih gradivnih jedinica postoje sinergističke interakcije se formiraju na nižim koncentracijama surfaktanata u poređenju sa monokomponentnim micelama. U doktorskoj disertaciji je ispitana termodinamička stabilnost binarnih mešovitih micela Brij S10 i Brij S20 surfaktanata sa polisorbatom 20, polisorbatom 60 i polisorbatom 80 kao kosurfaktantima. Analiziran je uticaj građe odabranih nejonskih surfaktanata na fizičko-hemijske parametre i stabilnost njihovih mešovitih micela. Vrednosti kritične micelarne koncentracije su dobijene spektrofluorimetrijskim merenjima. Da bi se analizirao uticaj temperature na termodinamičku stabilnost micela, merenja su vršena na sledećim temperaturama: 273.15 K, 283.15 K, 293.15 K, 303.15 K i 313.15 K. Rezultati su tumačeni sa aspekta teorije regularnih rastvora (regular solution theory – RST), uz primenu Porterove jednačine. Na osnovu rezultata istraživanja, predloženi su modeli monokomponentnih i binarnih mešovitih micela. Utvrđeno je da u svim analiziranim binarnim mešovitim sistemima postoji dodatna entropija. Može se doneti zaključak da pretpostavka RST o isključivo entalpijskoj prirodi dodatne Gibsove energije nije primenljiva na ispitivane binarne sisteme. Utvrđeno je da postojanje razlike u dužini hidrofobnih segmenata monomera dodatno stabilizuje mešovitu micelu. Sa porastom temperature, ovaj stabilizacioni efekat entropijskog porekla postaje izraženiji. Prisustvo dvostruke veze u ugljovodoničnom lancu polisorbata 80 doprinosi povećanoj rigidnosti njegovih molekula. Rezultat je smanjena termodinamička stabilnost mešovitih micela koje sadrže polisorbat 80 u poređenju sa mešovitim micelama koje sadrže njegov zasićeni homolog, polisorbat 60. Utvrđeno je da razlika u dužini polarnih segmenata monomera koji grade mešovitu micelu utiče na stepen hidratacije micele, a time i na njenu stabilnost., The role of the micelles in pharmaceutical formulation lies in their ability to, when used as drug delivery systems, increase the bioavailability of the drug and enhance its pharmacokinetic profile. Micelles may modify the permeability of biomembranes, enable controlled release from drug delivery systems, stabilize the drug, etc. By combining different surfactants as building units it is possible to engineer micelles with favorable physicochemical characteristics. Also, the mixed micelles between whose building units synergistic interactions exist are formed on lower concentrations of surfactants in comparison to single-component micelles. In the doctoral dissertation the thermodynamic stability of binary mixed micelles built of Brij S10 and Brij S20 with polysorbate 20, polysorbate 60 and polysorbate 80 as co-surfactants is examined. The influence of the structure of selected nonionic surfactants on physicochemical parameters and the stability of their mixed micelles is analyzed. Critical micelle concentration values were obtained by spectrofluorimetric measurements. In order to analyze the influence of the temperature on the micelles’ thermodynamic stability, measurements were conducted on following temperatures: 273.15 K, 283.15 K, 293.15 K, 303.15 K and 313.15 K. Obtained results were studied using regular solution theory (RST) and Porter’s equation. Based on the research results, models of both single-component and binary mixed micelles are introduced. It is deduced that in all analyzed binary mixed systems the excess entropy exists. A conclusion can be made that the assumption of RST regarding solely enthalpic nature of the excess Gibbs energy is not applicable to investigated binary systems. The difference in the length of the hydrophobic segments of monomers additionally stabilizes the mixed micelle. With the increase in the temperature, this stabilizing effect of the entropic nature is more noticeable. The existence of the double bond in polysorbate 80 hydrocarbon chain contributes to the increased rigidity of its molecules. As a result, the thermodynamic stability of the mixed micelles containing polysorbate 80 is lesser than the stability of the mixed micelles containing its saturated homologue, polysorbate 60. It is determined that the difference in length of polar segments of mixed micelle monomers affects the micelle hydration and therefore, its stability.

Razvoj savremenih sistema za ciljanu aplikaciju farmakološki aktivne supstance zasniva se na postojanju interakcija između funkcionalnih grupa makromolekula i površinski aktivne materije što omogućava kontrolisano oslobađanje, smanjenu toksičnost i bolji režim doziranja leka. Prisustvo tenzida, kako se jos površinski aktivne materije nazivaju, u niskim koncentracijima može značajno da izmeni konformaciju makromolekula i viskozitet sistema, i samim tim proširi mogućnosti primene modifikovanjem svojstava. Stoga je poznavanje fizičko-hemijskih osobina vodenih rastvora makromolekul-površinski aktivna materija neophodno radi dobijanja adekvatnog finalnog proizvoda unapređenih osobina uz primenu optimalnih koncentracija pomoćnih supstanci. U radu su prikazani rezultati ispitivanja uticaja natrijum lauril sulfata, predstavnika anjonskih tenzida, odnosno polioksietilen (20) sorbitan monooleata, kao široko korišćenog nejonskog tenzida na fizičko-hemijske osobine vodenih rastvora makromolekula karbomera 940 i ksantan gume. U cilju potpunog razumevanja ovih sistema, čiste komponente su prvo analizirane infracrvenom spektroskopijom primenom Fourierove tranformacije. Ponašanje karbomera 940 odnosno ksantan gume u prisustvu tenzida, ispitano je kombinacijom različitih tehnika (viskozimetrije, konduktometrije, tenziometrije, spektroskopije, spektrofluorimetrije, skenirajuće elektronske mikroskopije) koje pružaju uporedive rezultate. Određene vrednosti interakcionih parametara, potvrdjuju hipotezu o postojanju međudejstva između karbomera 940/ksantan gume i ispitivanih tenzida i ukazuju da povećanje koncentracije makromolekula u rastvoru uslovljava širenje opsega interakcije. Tenzidom indukovane promene konformacije ksantan gume odnosno karbomera 940 potvrđene su i na mikroskopskom nivou. Takođe, rezultati uticaja ispitivanih tenzida na osobine vodenih rastvora smeša karbomera 940 i ksantan gume dobijeni su istim tehnikama. Međudejstvom dva različita polimera bez dodatne sinteze na jeftin i brz način mogu se postići željene karakteristike sistema. Na osnovu eksperimentalnih rezultata definisani su matematički modeli primenom metodologije odzivnih površina i višestruke linearne regresije, čija je validnost statistički potvrđena te se mogu primeniti u optimizaciji i predviđanju fizičko-hemijskih osobina vodenih rastvora analiziranih binarnih sistema., The possible interactions between polymers and surfactants are of great interest in the development of drug delivery systems, where they improve therapeutic efficiency by the controlled release and reduced toxicity. The addition of even a small amount of surfactant could change the physico-chemical properties of polymer dispersions in terms of viscosity and stability of the system and, consequently, enlarge possibilities for their application. Therefore, understanding the physico-chemical properties of polymer-surfactant aqueous solutions are necessary in order to optimize the formulation of these compounds and consequently to get product with acceptable properties and desired effect. In this thesis the physico-chemical changes of carbomer 940 and xanthan gum influenced by different surfactants were investigated. Widely used anionic surfactant sodium dodecyl sulfate, and nonionic polyoxyethylene (20) sorbitan monooleate were used. In order to completely understand the mechanism of interaction the pure polymers and surfactants were tested by Fourier transform infrared spectrometer. The behaviour of carbomer 940 as well as xanthan gum in the presence of examined surfactants were analysed by the combination of different techniques such as viscometry, conductometry, tensiometry, spectrophotometry, fluorimetry and scanning electron microscopy. The obtained results confirmed the existence of interactions between carbomer 940 / xanthan gum and tested surfactants. Furthermore, the interaction parameters were determined and the polymer saturation points for both surfactants increased with the increase in carbomer 940 and xanthan gum content, respectively. Additionally, the surfactant induced microstructural changes of carbomer 940 as well as xanthan gum were confirmed. Moreover, the physico-chemical properties of the mixture of carbomer 940 and xanthan gum influenced by the addition of anionic and nonionic surfactant were examined by the same techniques. Without additional synthesis the desired characteristics of the system could be achieved by optimizing the interaction between two different polymers. The obtained results were analysed by response surface methodology and multiple linear regression analysis. The defined mathematical models could be used to optimize and predict physico-chemical properties of aqueous solutions of the tested binary systems.