TY  - THES
AU  - Kulaš, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4973
AB  - Kadmijum je jedan od najtoksičnijih teških metala kojem je opšta populacija izložena najvećim delom preko zagađene hrane. Iako je poznato da se kadmijum unet u organizam oralnim putem deponuje u plućima, retki su podaci o imunskom odgovoru u plućima na ovaj metal. Imunomodulatorni efekat kadmijuma koji u organizam dospeva oralnim putem (30 dana u vodi za piće) je ispitan u fiziološkim uslovima merenjem promena u ćelijskim i molekulskim mehanizmima imunskog odgovora na neletalne doze metala (5 i 50 mg/l) kod pacova i u patofiziološkim uslovima infekcije izazvane oportunističkom gljivom Aspergillus fumigatus. Ispitana je i uloga aril-ugljovodoničnog receptora (AhR) u imunotoksičnosti kadmijuma. U fiziološkim uslovima, prisustvo kadmijuma u plućima je izazvalo oksidativni stres, inflamaciju i oštećenje tkiva. Kadmijum je ispoljio diferencijalne efekte na aktivnosti leukocita pluća (nepromenjena produkcija reaktivnih oblika kiseonika i azota, inhibicija IL-1β i TNF, stimulacija MPO i IFN-γ) pri čemu su efekti kadmijuma na produkciju citokina posredovani aktivacijom AhR. U patofiziološkim uslovima infekcije izazvane gljivom A. fumigatus, kadmijum je doveo do efikasnijeg uklanjanja gljive iz tkiva (direktno je suprimirao rast gljive, povećao broj peharastih ćelija i produkciju mukusa i doveo do intenzivnije diferencijacije T-ćelija u pravcu Th17 T-ćelija u regionalnim limfnim čvorovima i njihove veće aktivnosti u tkivu pluća). Intenzivniji odgovor na gljivu kod jedinki koje su pile kadmijum je uzrokovao veće oštećenje tkiva pluća. Proinflamatorno mikrookruženje u plućima koje uspostavlja kadmijum, čini ovaj teški metal faktorom rizika za razvoj hronične inflamacije niskog stepena u plućima što bi moglo da utiče na osetljivost organizma u različitim patofiziološkim uslovima.
AB  - Cadmium is one of the most toxic heavy metals to which the general population is exposed mostly through contaminated food. Although cadmium taken orally is known to be deposited in the lungs, there is little evidence of an immune response in the lungs to this metal. The immunomodulatory effect of cadmium reaching the body orally (30 days in drinking water) was examined under physiological conditions by measuring changes in cellular and molecular mechanisms of the immune response to non-lethal metal doses (5 and 50 mg/l) in rats and pathophysiological conditions of infection caused by opportunistic fungus Aspergillus fumigatus. The role of the aryl hydrocarbon receptor (AhR) in cadmium immunotoxicity was also investigated. Under physiological conditions, the presence of cadmium in the lungs caused oxidative stress, inflammation, and tissue damage. Cadmium exhibited differential effects on lung leukocyte activity (unchanged production of reactive oxygen species and nitrogen, inhibition of IL-1β and TNF, stimulation of MPO and IFN-γ) with cadmium effects on cytokine production mediated by AhR activation. In the pathophysiological conditions of infection caused by A. fumigatus, cadmium led to more efficient removal of fungus from tissues (directly suppressing fungal growth, increasing goblet cell count and mucus production, and leding to more intense T-cell differentiation towards Th17 T-cells in regional lymph nodes and their greater activity in lung tissue). A more intense response to the fungus in individuals who drank cadmium caused greater damage to lung tissue. The proinflammatory microenvironment in the lungs established by cadmium makes this heavy metal a risk factor for the development of low-grade chronic inflammation in the lungs, which could affect the sensitivity of the organism in various pathophysiological conditions.
PB  - Belgrade: Faculty of Biology, University of Belgrade
T2  - Faculty of Biology, University of Belgrade
T1  - Efekat oralne primene kadmijum-hlorida na imunski odgovor u plućima pacova u fiziološkim i patofiziološkim uslovima infekcije izazvane oportunističkom gljivom Аspergillus fumigatus
T1  - Effects of oral cadmium-chloride intake on immune response in the lungs of rats in physiological and pathophysiological conditions of infection with opportunistic fungus Aspergillus fumigatus
SP  - 1
EP  - 69
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4973
ER  - 

@phdthesis{
author = "Kulaš, Jelena",
year = "2022",
abstract = "Kadmijum je jedan od najtoksičnijih teških metala kojem je opšta populacija izložena najvećim delom preko zagađene hrane. Iako je poznato da se kadmijum unet u organizam oralnim putem deponuje u plućima, retki su podaci o imunskom odgovoru u plućima na ovaj metal. Imunomodulatorni efekat kadmijuma koji u organizam dospeva oralnim putem (30 dana u vodi za piće) je ispitan u fiziološkim uslovima merenjem promena u ćelijskim i molekulskim mehanizmima imunskog odgovora na neletalne doze metala (5 i 50 mg/l) kod pacova i u patofiziološkim uslovima infekcije izazvane oportunističkom gljivom Aspergillus fumigatus. Ispitana je i uloga aril-ugljovodoničnog receptora (AhR) u imunotoksičnosti kadmijuma. U fiziološkim uslovima, prisustvo kadmijuma u plućima je izazvalo oksidativni stres, inflamaciju i oštećenje tkiva. Kadmijum je ispoljio diferencijalne efekte na aktivnosti leukocita pluća (nepromenjena produkcija reaktivnih oblika kiseonika i azota, inhibicija IL-1β i TNF, stimulacija MPO i IFN-γ) pri čemu su efekti kadmijuma na produkciju citokina posredovani aktivacijom AhR. U patofiziološkim uslovima infekcije izazvane gljivom A. fumigatus, kadmijum je doveo do efikasnijeg uklanjanja gljive iz tkiva (direktno je suprimirao rast gljive, povećao broj peharastih ćelija i produkciju mukusa i doveo do intenzivnije diferencijacije T-ćelija u pravcu Th17 T-ćelija u regionalnim limfnim čvorovima i njihove veće aktivnosti u tkivu pluća). Intenzivniji odgovor na gljivu kod jedinki koje su pile kadmijum je uzrokovao veće oštećenje tkiva pluća. Proinflamatorno mikrookruženje u plućima koje uspostavlja kadmijum, čini ovaj teški metal faktorom rizika za razvoj hronične inflamacije niskog stepena u plućima što bi moglo da utiče na osetljivost organizma u različitim patofiziološkim uslovima., Cadmium is one of the most toxic heavy metals to which the general population is exposed mostly through contaminated food. Although cadmium taken orally is known to be deposited in the lungs, there is little evidence of an immune response in the lungs to this metal. The immunomodulatory effect of cadmium reaching the body orally (30 days in drinking water) was examined under physiological conditions by measuring changes in cellular and molecular mechanisms of the immune response to non-lethal metal doses (5 and 50 mg/l) in rats and pathophysiological conditions of infection caused by opportunistic fungus Aspergillus fumigatus. The role of the aryl hydrocarbon receptor (AhR) in cadmium immunotoxicity was also investigated. Under physiological conditions, the presence of cadmium in the lungs caused oxidative stress, inflammation, and tissue damage. Cadmium exhibited differential effects on lung leukocyte activity (unchanged production of reactive oxygen species and nitrogen, inhibition of IL-1β and TNF, stimulation of MPO and IFN-γ) with cadmium effects on cytokine production mediated by AhR activation. In the pathophysiological conditions of infection caused by A. fumigatus, cadmium led to more efficient removal of fungus from tissues (directly suppressing fungal growth, increasing goblet cell count and mucus production, and leding to more intense T-cell differentiation towards Th17 T-cells in regional lymph nodes and their greater activity in lung tissue). A more intense response to the fungus in individuals who drank cadmium caused greater damage to lung tissue. The proinflammatory microenvironment in the lungs established by cadmium makes this heavy metal a risk factor for the development of low-grade chronic inflammation in the lungs, which could affect the sensitivity of the organism in various pathophysiological conditions.",
publisher = "Belgrade: Faculty of Biology, University of Belgrade",
journal = "Faculty of Biology, University of Belgrade",
title = "Efekat oralne primene kadmijum-hlorida na imunski odgovor u plućima pacova u fiziološkim i patofiziološkim uslovima infekcije izazvane oportunističkom gljivom Аspergillus fumigatus, Effects of oral cadmium-chloride intake on immune response in the lungs of rats in physiological and pathophysiological conditions of infection with opportunistic fungus Aspergillus fumigatus",
pages = "1-69",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4973"
}

Kulaš, J.. (2022). Efekat oralne primene kadmijum-hlorida na imunski odgovor u plućima pacova u fiziološkim i patofiziološkim uslovima infekcije izazvane oportunističkom gljivom Аspergillus fumigatus. in Faculty of Biology, University of Belgrade
Belgrade: Faculty of Biology, University of Belgrade., 1-69.
https://hdl.handle.net/21.15107/rcub_ibiss_4973

Kulaš J. Efekat oralne primene kadmijum-hlorida na imunski odgovor u plućima pacova u fiziološkim i patofiziološkim uslovima infekcije izazvane oportunističkom gljivom Аspergillus fumigatus. in Faculty of Biology, University of Belgrade. 2022;:1-69.
https://hdl.handle.net/21.15107/rcub_ibiss_4973 .

Kulaš, Jelena, "Efekat oralne primene kadmijum-hlorida na imunski odgovor u plućima pacova u fiziološkim i patofiziološkim uslovima infekcije izazvane oportunističkom gljivom Аspergillus fumigatus" in Faculty of Biology, University of Belgrade (2022):1-69,
https://hdl.handle.net/21.15107/rcub_ibiss_4973 .

TY  - JOUR
AU  - Tucović, Dina
AU  - Mirkov, Ivana
AU  - Kulaš, Jelena
AU  - Zeljković, Milica
AU  - Popović, Dušanka
AU  - Zolotarevski, Lidija
AU  - Đuđjić, Slađana
AU  - Mutić, Jelena
AU  - Kataranovski, Milena
AU  - Popov Aleksandrov, Aleksandra
PY  - 2020
UR  - internal-pdf://Tucovic et al. - 2020 - Dermatotoxicity of oral cadmium is strain-dependent and related to differences in skin stress response and infla.pdf
UR  - http://www.ncbi.nlm.nih.gov/pubmed/31924569
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3594
AB  - Adverse effects of non-occupational exposure to cadmium (Cd) are increasingly acknowledged. Since our previous study has showed that orally acquired Cd affects skin, the contribution of genetic background to dermatotoxicity of oral cadmium was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), which differed in response to chemicals. While similar accumulation of Cd in the skin of both strains was noted, the skin response to the metal differed. DA rat individuals mounted antioxidant enzyme defense in the skin already at lower Cd dose, in contrast to AO rats which reacted to higher metal dose solely (and less pronounced), implying higher susceptibility of DA strain to Cd dermatotoxicity. Epidermal cells from both strains developed stress response, but higher intensity of antioxidant response in AO rats implied this strain`s better ability to defend against Cd insult. Cd induced epidermal cells' proinflammatory cytokine response only in DA rats. Increased IL-10 seems responsible for the lack of response in AO rats. Differences in the pattern of skin/epidermal cell responsiveness to cadmium give a new insight into repercussion of genetic variability to dermatotoxicity of orally acquired cadmium, bearing relevance for variations in the link between dietary cadmium and inflammation-based skin pathologies.
T2  - Environmental Toxicology and Pharmacology
T1  - Dermatotoxicity of oral cadmium is strain-dependent and related to differences in skin stress response and inflammatory/immune activity.
VL  - 75
DO  - 10.1016/j.etap.2020.103326
SP  - 103326
ER  - 

@article{
author = "Tucović, Dina and Mirkov, Ivana and Kulaš, Jelena and Zeljković, Milica and Popović, Dušanka and Zolotarevski, Lidija and Đuđjić, Slađana and Mutić, Jelena and Kataranovski, Milena and Popov Aleksandrov, Aleksandra",
year = "2020",
abstract = "Adverse effects of non-occupational exposure to cadmium (Cd) are increasingly acknowledged. Since our previous study has showed that orally acquired Cd affects skin, the contribution of genetic background to dermatotoxicity of oral cadmium was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), which differed in response to chemicals. While similar accumulation of Cd in the skin of both strains was noted, the skin response to the metal differed. DA rat individuals mounted antioxidant enzyme defense in the skin already at lower Cd dose, in contrast to AO rats which reacted to higher metal dose solely (and less pronounced), implying higher susceptibility of DA strain to Cd dermatotoxicity. Epidermal cells from both strains developed stress response, but higher intensity of antioxidant response in AO rats implied this strain`s better ability to defend against Cd insult. Cd induced epidermal cells' proinflammatory cytokine response only in DA rats. Increased IL-10 seems responsible for the lack of response in AO rats. Differences in the pattern of skin/epidermal cell responsiveness to cadmium give a new insight into repercussion of genetic variability to dermatotoxicity of orally acquired cadmium, bearing relevance for variations in the link between dietary cadmium and inflammation-based skin pathologies.",
journal = "Environmental Toxicology and Pharmacology",
title = "Dermatotoxicity of oral cadmium is strain-dependent and related to differences in skin stress response and inflammatory/immune activity.",
volume = "75",
doi = "10.1016/j.etap.2020.103326",
pages = "103326"
}

Tucović, D., Mirkov, I., Kulaš, J., Zeljković, M., Popović, D., Zolotarevski, L., Đuđjić, S., Mutić, J., Kataranovski, M.,& Popov Aleksandrov, A.. (2020). Dermatotoxicity of oral cadmium is strain-dependent and related to differences in skin stress response and inflammatory/immune activity.. in Environmental Toxicology and Pharmacology, 75, 103326.
https://doi.org/10.1016/j.etap.2020.103326

Tucović D, Mirkov I, Kulaš J, Zeljković M, Popović D, Zolotarevski L, Đuđjić S, Mutić J, Kataranovski M, Popov Aleksandrov A. Dermatotoxicity of oral cadmium is strain-dependent and related to differences in skin stress response and inflammatory/immune activity.. in Environmental Toxicology and Pharmacology. 2020;75:103326.
doi:10.1016/j.etap.2020.103326 .

Tucović, Dina, Mirkov, Ivana, Kulaš, Jelena, Zeljković, Milica, Popović, Dušanka, Zolotarevski, Lidija, Đuđjić, Slađana, Mutić, Jelena, Kataranovski, Milena, Popov Aleksandrov, Aleksandra, "Dermatotoxicity of oral cadmium is strain-dependent and related to differences in skin stress response and inflammatory/immune activity." in Environmental Toxicology and Pharmacology, 75 (2020):103326,
https://doi.org/10.1016/j.etap.2020.103326 . .

TY  - JOUR
AU  - Mirković, Nemanja
AU  - Kulaš, Jelena
AU  - Miloradović, Zorana
AU  - Miljković, Marija
AU  - Tucović, Dina
AU  - Miocionović, Jelena
AU  - Jovčić, Branko
AU  - Mirkov, Ivana
AU  - Kojić, Milan
PY  - 2020
UR  - internal-pdf://Mirkovic et al. - 2020 - Lactolisterin BU-producer Lactococcus lactis subsp. lactis BGBU1-4 Bio-control of Listeria monocytogenes and St.pdf
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3593
AB  - In last two decades, there has been a strong trend in the application of lactic acid bacteria as adjunctive cultures to control growth of spoilage and pathogenic bacteria in food. One of the most important properties that contribute to the application of these bacteria is the production of antimicrobial molecules. Lactococcus lactis subsp. lactis BGBU1-4, isolated from traditional brined cheese, produces thermostable bacteriocin named lactolisterin BU, with broad spectrum of activity against spoilage bacteria and foodborne pathogens. In this study, effect of strain BGBU1-4, as adjunct culture, on the numbers of Listeria monocytogenes ATCC19111 and Staphylococcus aureus LMM322 in artificially contaminated Quark-type, soft acid coagulated cheese, was examined. In addition, we analyzed influence of BGBU1-4 on chemical and sensory properties of the cheese, as well as immunological response of Albino oxford rats fed with Quark-type of cheese made using BGBU1-4 as adjunct culture. Results of this study revealed antibacterial potential of strain BGBU1-4 against L. monocytogenes ATCC19111 and S. aureus LMM322 in Quark-type cheese during 21 days of storage at 4 °C. Also, it was noticed the ability of BGBU1-4 to control the spontaneously grown yeasts and molds. Chemical composition and pH values of cheese containing BGBU1-4 were unchanged in comparison to control. The sensory quality scores showed that there was difference between cheese with and without adjunct culture in terms of flavor and oral texture, while for the odor and appearance no differences between two cheese variants were scored. Results of the immunological response of Albino rats fed with Quark-type cheese containing BGBU1-4 indicate absence of systematic inflammation. However, increased pro-inflammatory cytokines content (IL-1β, IL-6, IL-17) in intestine of rats fed with cheese containing BGBU1-4, concomitantly with unchanged anti-inflammatory cytokines suggests disruption of gut homeostasis and inflammation in this tissue. The changes caused by BGBU1-4 are reversible, system returns into homeostasis seven days after cessation of feeding with cheese containing BGBU1-4.
T2  - Food Control
T1  - Lactolisterin BU-producer Lactococcus lactis subsp. lactis BGBU1-4: Bio-control of Listeria monocytogenes and Staphylocococcus aureus in fresh soft cheese and effect on immunological response of rats
VL  - 111
DO  - 10.1016/j.foodcont.2019.107076
SP  - 107076
ER  - 

@article{
author = "Mirković, Nemanja and Kulaš, Jelena and Miloradović, Zorana and Miljković, Marija and Tucović, Dina and Miocionović, Jelena and Jovčić, Branko and Mirkov, Ivana and Kojić, Milan",
year = "2020",
abstract = "In last two decades, there has been a strong trend in the application of lactic acid bacteria as adjunctive cultures to control growth of spoilage and pathogenic bacteria in food. One of the most important properties that contribute to the application of these bacteria is the production of antimicrobial molecules. Lactococcus lactis subsp. lactis BGBU1-4, isolated from traditional brined cheese, produces thermostable bacteriocin named lactolisterin BU, with broad spectrum of activity against spoilage bacteria and foodborne pathogens. In this study, effect of strain BGBU1-4, as adjunct culture, on the numbers of Listeria monocytogenes ATCC19111 and Staphylococcus aureus LMM322 in artificially contaminated Quark-type, soft acid coagulated cheese, was examined. In addition, we analyzed influence of BGBU1-4 on chemical and sensory properties of the cheese, as well as immunological response of Albino oxford rats fed with Quark-type of cheese made using BGBU1-4 as adjunct culture. Results of this study revealed antibacterial potential of strain BGBU1-4 against L. monocytogenes ATCC19111 and S. aureus LMM322 in Quark-type cheese during 21 days of storage at 4 °C. Also, it was noticed the ability of BGBU1-4 to control the spontaneously grown yeasts and molds. Chemical composition and pH values of cheese containing BGBU1-4 were unchanged in comparison to control. The sensory quality scores showed that there was difference between cheese with and without adjunct culture in terms of flavor and oral texture, while for the odor and appearance no differences between two cheese variants were scored. Results of the immunological response of Albino rats fed with Quark-type cheese containing BGBU1-4 indicate absence of systematic inflammation. However, increased pro-inflammatory cytokines content (IL-1β, IL-6, IL-17) in intestine of rats fed with cheese containing BGBU1-4, concomitantly with unchanged anti-inflammatory cytokines suggests disruption of gut homeostasis and inflammation in this tissue. The changes caused by BGBU1-4 are reversible, system returns into homeostasis seven days after cessation of feeding with cheese containing BGBU1-4.",
journal = "Food Control",
title = "Lactolisterin BU-producer Lactococcus lactis subsp. lactis BGBU1-4: Bio-control of Listeria monocytogenes and Staphylocococcus aureus in fresh soft cheese and effect on immunological response of rats",
volume = "111",
doi = "10.1016/j.foodcont.2019.107076",
pages = "107076"
}

Mirković, N., Kulaš, J., Miloradović, Z., Miljković, M., Tucović, D., Miocionović, J., Jovčić, B., Mirkov, I.,& Kojić, M.. (2020). Lactolisterin BU-producer Lactococcus lactis subsp. lactis BGBU1-4: Bio-control of Listeria monocytogenes and Staphylocococcus aureus in fresh soft cheese and effect on immunological response of rats. in Food Control, 111, 107076.
https://doi.org/10.1016/j.foodcont.2019.107076

Mirković N, Kulaš J, Miloradović Z, Miljković M, Tucović D, Miocionović J, Jovčić B, Mirkov I, Kojić M. Lactolisterin BU-producer Lactococcus lactis subsp. lactis BGBU1-4: Bio-control of Listeria monocytogenes and Staphylocococcus aureus in fresh soft cheese and effect on immunological response of rats. in Food Control. 2020;111:107076.
doi:10.1016/j.foodcont.2019.107076 .

Mirković, Nemanja, Kulaš, Jelena, Miloradović, Zorana, Miljković, Marija, Tucović, Dina, Miocionović, Jelena, Jovčić, Branko, Mirkov, Ivana, Kojić, Milan, "Lactolisterin BU-producer Lactococcus lactis subsp. lactis BGBU1-4: Bio-control of Listeria monocytogenes and Staphylocococcus aureus in fresh soft cheese and effect on immunological response of rats" in Food Control, 111 (2020):107076,
https://doi.org/10.1016/j.foodcont.2019.107076 . .

TY  - THES
AU  - Tucović, Dina
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3708
AB  - Štetni uticaji sredinske izloženosti kadmijumu (Cd), koji se odražavaju na različite organe, sve se više prepoznaju. Iako je poznato da topikalna primena Cd može uticati na vijabilnost ćelija kože, gotovo da nema podataka o efektu Cd na homeostatske procese ovog tkiva, uključujući efekte na imunski sistem kože, naročito nakon oralnog unosa. Efekti produženog izlaganja (30 dana) sredinski bitnim dozama Cd (5 i 50 ppm), ispitani su kod Dark Agouti (DA) i Albino Oxford (AO) pacova, koji se razlikuju u imunskom odgovoru na različite stimuluse. Pored efekta Cd na oksidativnu i imunsku/inflamatornu aktivnost kože, ispitana je reaktivnost kože na dodatni stimulus, dinitrohlorobenzen (DNCB) u reakciji kontaktne preosetljivosti. Uprkos sličnom deponovanju Cd u koži/ćelijama kože, kod DA soja već na 5ppm Cd zapaženo je oštećenje tkiva i veći intenzitet/različit obrazac oksidativnog i imunskog odgovora, ukazujući na veću osetljivost ovog soja na dermatotoksične efekte Cd. Iako su EĆ oba soja razvile stres odgovor na prisustvo Cd, intezivniji antioksidativni odgovor (povećanje GSH, viša ekspresija gena za MT-1 i -2, proteina za Nrf2, kao i ekspresije gena AHR puta) uz prisustvo apoptoze samo kod AO soja, ukazuje na bolju sposobnost zaštite ovog soja od štetnog efekta Cd. Proinflamatorni odgovor zapažen je samo kod EĆ DA soja (povećanje IL-1β, TNF i IL-6), a povećanje IL-10 kao potencijalnog mehanizma zaštite kod AO soja. Ipak, nakon topikalne primene DNCB razvija se inflamatorni odgovor kod oba soja, sugerišući da se kod AO pacova probijaju zaštitni mehanizmi koji su se održavali nakon primene samog Cd (makar na 50 ppm Cd). Ova studija može biti korisna prilikom ispitivanja veze oralnog unosa Cd i različite osetljivosti kože na razvoj zapaljenskih reakcija i patoloških stanja.
AB  - Harmful effects of environmental Cd exposure, which affect different organs, are being increasingly recognized. Although it is known that topical Cd administration may affect skin cell viability, there is a paucity of data concerning Cd effect on the homeostatic processes of this tissue, including effects on the skin's immune system, especially after oral intake. The effects of prolonged exposure (30 days) to the two environmentally relevant Cd doses (5 and 50 ppm) were examined in Dark Agouti (DA) and Albino Oxford (AO) rats, which differ in the immune responses to different stimuli. In addition to the Cd effects on the oxidative and immune/inflammatory skin activity, the reactivity of skin after additional dinitrochlorobenzene (DNCB) stimulus during contact hypersensitivity reaction (CHS), was examined. Despite similar Cd deposition in skin/skin cells, tissue damage and a higher intensity/different pattern of oxidative and immune responses were observed in DA strain already at 5 ppm Cd, indicating a higher sensitivity of this strain to the dermatotoxic Cd effects. Although epidermal cells (ECs) of both strains developed stress response to the Cd presence, a more intensive antioxidative response (an increase of GSH, a higher level of gene expression for MT-1 and MT-2, proteins for Nrf2, as well as the genes of AHR pathway) with the presence of apoptosis only in AO strain, indicates a better protection capability of this strain from deleterious Cd effect. The proinflammatory response was observed only in the ECs of DA strain (an increase in IL-1β, TNF and IL-6), as well as IL-10 increase in AO strain as a potential protection mechanism. Nevertheless, after topical administration of DNCB, an inflammatory response develops in both strains, indicating the breakthrough of protective mechanisms that persisted in AO rats after oral Cd intake (at least at 50 ppm Cd). This study may be useful for examining the relationship between oral Cd intake and different skin sensitivity to the development of inflammatory responses and pathological conditions.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Efekti oralnog unosa kadmijuma na imunski sistem kože pacova
T1  - Effects of oral cadmium intake in skin reactivity in rats
SP  - 1
EP  - 137
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3708
ER  - 

@phdthesis{
author = "Tucović, Dina",
year = "2020",
abstract = "Štetni uticaji sredinske izloženosti kadmijumu (Cd), koji se odražavaju na različite organe, sve se više prepoznaju. Iako je poznato da topikalna primena Cd može uticati na vijabilnost ćelija kože, gotovo da nema podataka o efektu Cd na homeostatske procese ovog tkiva, uključujući efekte na imunski sistem kože, naročito nakon oralnog unosa. Efekti produženog izlaganja (30 dana) sredinski bitnim dozama Cd (5 i 50 ppm), ispitani su kod Dark Agouti (DA) i Albino Oxford (AO) pacova, koji se razlikuju u imunskom odgovoru na različite stimuluse. Pored efekta Cd na oksidativnu i imunsku/inflamatornu aktivnost kože, ispitana je reaktivnost kože na dodatni stimulus, dinitrohlorobenzen (DNCB) u reakciji kontaktne preosetljivosti. Uprkos sličnom deponovanju Cd u koži/ćelijama kože, kod DA soja već na 5ppm Cd zapaženo je oštećenje tkiva i veći intenzitet/različit obrazac oksidativnog i imunskog odgovora, ukazujući na veću osetljivost ovog soja na dermatotoksične efekte Cd. Iako su EĆ oba soja razvile stres odgovor na prisustvo Cd, intezivniji antioksidativni odgovor (povećanje GSH, viša ekspresija gena za MT-1 i -2, proteina za Nrf2, kao i ekspresije gena AHR puta) uz prisustvo apoptoze samo kod AO soja, ukazuje na bolju sposobnost zaštite ovog soja od štetnog efekta Cd. Proinflamatorni odgovor zapažen je samo kod EĆ DA soja (povećanje IL-1β, TNF i IL-6), a povećanje IL-10 kao potencijalnog mehanizma zaštite kod AO soja. Ipak, nakon topikalne primene DNCB razvija se inflamatorni odgovor kod oba soja, sugerišući da se kod AO pacova probijaju zaštitni mehanizmi koji su se održavali nakon primene samog Cd (makar na 50 ppm Cd). Ova studija može biti korisna prilikom ispitivanja veze oralnog unosa Cd i različite osetljivosti kože na razvoj zapaljenskih reakcija i patoloških stanja., Harmful effects of environmental Cd exposure, which affect different organs, are being increasingly recognized. Although it is known that topical Cd administration may affect skin cell viability, there is a paucity of data concerning Cd effect on the homeostatic processes of this tissue, including effects on the skin's immune system, especially after oral intake. The effects of prolonged exposure (30 days) to the two environmentally relevant Cd doses (5 and 50 ppm) were examined in Dark Agouti (DA) and Albino Oxford (AO) rats, which differ in the immune responses to different stimuli. In addition to the Cd effects on the oxidative and immune/inflammatory skin activity, the reactivity of skin after additional dinitrochlorobenzene (DNCB) stimulus during contact hypersensitivity reaction (CHS), was examined. Despite similar Cd deposition in skin/skin cells, tissue damage and a higher intensity/different pattern of oxidative and immune responses were observed in DA strain already at 5 ppm Cd, indicating a higher sensitivity of this strain to the dermatotoxic Cd effects. Although epidermal cells (ECs) of both strains developed stress response to the Cd presence, a more intensive antioxidative response (an increase of GSH, a higher level of gene expression for MT-1 and MT-2, proteins for Nrf2, as well as the genes of AHR pathway) with the presence of apoptosis only in AO strain, indicates a better protection capability of this strain from deleterious Cd effect. The proinflammatory response was observed only in the ECs of DA strain (an increase in IL-1β, TNF and IL-6), as well as IL-10 increase in AO strain as a potential protection mechanism. Nevertheless, after topical administration of DNCB, an inflammatory response develops in both strains, indicating the breakthrough of protective mechanisms that persisted in AO rats after oral Cd intake (at least at 50 ppm Cd). This study may be useful for examining the relationship between oral Cd intake and different skin sensitivity to the development of inflammatory responses and pathological conditions.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Efekti oralnog unosa kadmijuma na imunski sistem kože pacova, Effects of oral cadmium intake in skin reactivity in rats",
pages = "1-137",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3708"
}

Tucović, D.. (2020). Efekti oralnog unosa kadmijuma na imunski sistem kože pacova. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-137.
https://hdl.handle.net/21.15107/rcub_ibiss_3708

Tucović D. Efekti oralnog unosa kadmijuma na imunski sistem kože pacova. in University of Belgrade, Faculty of Biology. 2020;:1-137.
https://hdl.handle.net/21.15107/rcub_ibiss_3708 .

Tucović, Dina, "Efekti oralnog unosa kadmijuma na imunski sistem kože pacova" in University of Belgrade, Faculty of Biology (2020):1-137,
https://hdl.handle.net/21.15107/rcub_ibiss_3708 .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Lazović, B.
AU  - Glamočlija, Jasmina
AU  - Kataranovski, Milena
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S1156523318301239?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3247
AB  - Aspergillosis represents a spectrum of fungal diseases which are caused by fungi of the genus Aspergillus. Animal models have been developed and used to address immune-based mechanisms of defense against these fungi. Invertebrate models enabled mass screening of virulence attributes of Aspergillus species as well as mechanisms of acquired resistance to antifungal agents. This review represents a concise view of cellular and humoral participants in an immune response to Aspergillus gained mostly from rodent models of aspergillosis. The survey of immune defense mechanisms was given, including the role of innate immune cells (macrophages, neutrophils, monocytes, eosinophils, innate-like lymphocytes) and receptors in antifungal response, the significance of dendritic cells in activation of specific adaptive T cell-mediated immune responses and the regulatory mechanisms of excessive response. Insight into innate immune defense mechanisms gained using non-vertebrate models of infections with Aspergillus sp. was given as well. The contribution of animal models to the current knowledge of immune mechanisms of resistance or susceptibility to these fungi was stressed and the significance of data gained from these models in forming the basis for the design of therapeutic strategies in prevention and/or treatment of aspergillosis was pointed out.
T2  - Journal de Mycologie Médicale
T1  - Usefulness of animal models of aspergillosis in studying immunity against Aspergillus infections.
IS  - 1
VL  - 29
DO  - 10.1016/j.mycmed.2019.01.006
SP  - 84
EP  - 96
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Lazović, B. and Glamočlija, Jasmina and Kataranovski, Milena",
year = "2019",
abstract = "Aspergillosis represents a spectrum of fungal diseases which are caused by fungi of the genus Aspergillus. Animal models have been developed and used to address immune-based mechanisms of defense against these fungi. Invertebrate models enabled mass screening of virulence attributes of Aspergillus species as well as mechanisms of acquired resistance to antifungal agents. This review represents a concise view of cellular and humoral participants in an immune response to Aspergillus gained mostly from rodent models of aspergillosis. The survey of immune defense mechanisms was given, including the role of innate immune cells (macrophages, neutrophils, monocytes, eosinophils, innate-like lymphocytes) and receptors in antifungal response, the significance of dendritic cells in activation of specific adaptive T cell-mediated immune responses and the regulatory mechanisms of excessive response. Insight into innate immune defense mechanisms gained using non-vertebrate models of infections with Aspergillus sp. was given as well. The contribution of animal models to the current knowledge of immune mechanisms of resistance or susceptibility to these fungi was stressed and the significance of data gained from these models in forming the basis for the design of therapeutic strategies in prevention and/or treatment of aspergillosis was pointed out.",
journal = "Journal de Mycologie Médicale",
title = "Usefulness of animal models of aspergillosis in studying immunity against Aspergillus infections.",
number = "1",
volume = "29",
doi = "10.1016/j.mycmed.2019.01.006",
pages = "84-96"
}

Mirkov, I., Popov Aleksandrov, A., Lazović, B., Glamočlija, J.,& Kataranovski, M.. (2019). Usefulness of animal models of aspergillosis in studying immunity against Aspergillus infections.. in Journal de Mycologie Médicale, 29(1), 84-96.
https://doi.org/10.1016/j.mycmed.2019.01.006

Mirkov I, Popov Aleksandrov A, Lazović B, Glamočlija J, Kataranovski M. Usefulness of animal models of aspergillosis in studying immunity against Aspergillus infections.. in Journal de Mycologie Médicale. 2019;29(1):84-96.
doi:10.1016/j.mycmed.2019.01.006 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Lazović, B., Glamočlija, Jasmina, Kataranovski, Milena, "Usefulness of animal models of aspergillosis in studying immunity against Aspergillus infections." in Journal de Mycologie Médicale, 29, no. 1 (2019):84-96,
https://doi.org/10.1016/j.mycmed.2019.01.006 . .

TY  - CONF
AU  - Popović, Dušanka
AU  - Popov Aleksandrov, Aleksandra
AU  - Tucović, Dina
AU  - Kulaš, Jelena
AU  - Zeljković, Milica
AU  - Terzić-Vidojević, Amarela
AU  - Lukić, Jovana
AU  - Golić, Nataša
AU  - Mirkov, Ivana
AU  - Tolinački, Maja
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4793
AB  - The gut microbiome is very important for hosts’ proper essential functions, as microbiota influence both near and distant organs and disruption at any level of this complex relation can be underlying cause for many diseases. Both intestinal bacterial population and their metabolic products are involved in immune system development, activity and maintenance of immune homeostasis. Previous findings revealed differences in immune reactivity in Albino Oxford (AO) and Dark Agouti (DA) rat strains in various diseases models (such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, contact hypersensitivity reaction, pulmonary aspergillosis etc.), and in response to xenobiotics such as cadmium, warfarin, etc.
The aim of present study was to investigate microbial composition of gut (duodenum, jejunum, coecum and colon) and lungs of AO and DA rats using DGGE method. Although similar number of bacterial species were noted in both tissue and lumen of duodenum, bacterial composition differ between these two strains (solely 76.2% and 44.4% species were common in both strains tissue and lumen, respectively), while greater variability was noted in DA rats. Similar results were noted in jejunum. In contrast to duodenum and jejunum, higher number of bacterial species were detected in coecum (content) and colon (tissue and content) of AO rats. Around 50% of detected bacteria were present in both gut segments of both strains. Analysis of DGGE bands obtained from lung tissue revealed similar number of bacteria in both strains, but solely 54.5% were common. Further investigations will be directed to identification of bacterial species and try to connect observed differences in microbial composition with different immune reactivity in AO and DA rats.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches : abstract book
T1  - Variability of gut and lung microbiota in rat strains known to differ in reactivity to immune stimuly
SP  - 28
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4793
ER  - 

@conference{
author = "Popović, Dušanka and Popov Aleksandrov, Aleksandra and Tucović, Dina and Kulaš, Jelena and Zeljković, Milica and Terzić-Vidojević, Amarela and Lukić, Jovana and Golić, Nataša and Mirkov, Ivana and Tolinački, Maja",
year = "2019",
abstract = "The gut microbiome is very important for hosts’ proper essential functions, as microbiota influence both near and distant organs and disruption at any level of this complex relation can be underlying cause for many diseases. Both intestinal bacterial population and their metabolic products are involved in immune system development, activity and maintenance of immune homeostasis. Previous findings revealed differences in immune reactivity in Albino Oxford (AO) and Dark Agouti (DA) rat strains in various diseases models (such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, contact hypersensitivity reaction, pulmonary aspergillosis etc.), and in response to xenobiotics such as cadmium, warfarin, etc.
The aim of present study was to investigate microbial composition of gut (duodenum, jejunum, coecum and colon) and lungs of AO and DA rats using DGGE method. Although similar number of bacterial species were noted in both tissue and lumen of duodenum, bacterial composition differ between these two strains (solely 76.2% and 44.4% species were common in both strains tissue and lumen, respectively), while greater variability was noted in DA rats. Similar results were noted in jejunum. In contrast to duodenum and jejunum, higher number of bacterial species were detected in coecum (content) and colon (tissue and content) of AO rats. Around 50% of detected bacteria were present in both gut segments of both strains. Analysis of DGGE bands obtained from lung tissue revealed similar number of bacteria in both strains, but solely 54.5% were common. Further investigations will be directed to identification of bacterial species and try to connect observed differences in microbial composition with different immune reactivity in AO and DA rats.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches : abstract book",
title = "Variability of gut and lung microbiota in rat strains known to differ in reactivity to immune stimuly",
pages = "28",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4793"
}

Popović, D., Popov Aleksandrov, A., Tucović, D., Kulaš, J., Zeljković, M., Terzić-Vidojević, A., Lukić, J., Golić, N., Mirkov, I.,& Tolinački, M.. (2019). Variability of gut and lung microbiota in rat strains known to differ in reactivity to immune stimuly. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book
Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade., 28.
https://hdl.handle.net/21.15107/rcub_ibiss_4793

Popović D, Popov Aleksandrov A, Tucović D, Kulaš J, Zeljković M, Terzić-Vidojević A, Lukić J, Golić N, Mirkov I, Tolinački M. Variability of gut and lung microbiota in rat strains known to differ in reactivity to immune stimuly. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book. 2019;:28.
https://hdl.handle.net/21.15107/rcub_ibiss_4793 .

Popović, Dušanka, Popov Aleksandrov, Aleksandra, Tucović, Dina, Kulaš, Jelena, Zeljković, Milica, Terzić-Vidojević, Amarela, Lukić, Jovana, Golić, Nataša, Mirkov, Ivana, Tolinački, Maja, "Variability of gut and lung microbiota in rat strains known to differ in reactivity to immune stimuly" in Immunology at the Confluence of Multidisciplinary Approaches : abstract book (2019):28,
https://hdl.handle.net/21.15107/rcub_ibiss_4793 .

TY  - CONF
AU  - Kulaš, Jelena
AU  - Tucović, Dina
AU  - Zeljković, Milica
AU  - Popović, Dušanka
AU  - Popov Aleksandrov, Aleksandra
AU  - Kataranovski, Milena
AU  - Mirkov, Ivana
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4794
AB  - Cadmium (Cd) is a heavy metal widely spread in the environment and significant water and food contaminant. This metal exerts toxic effects in various tissues thus representing great threat to human health, and our previous study showed that oral consumption of Cd (in water for 30 days) increased the metal deposition and exerted immunomodulatory effects in lung leukocytes. Although the most studied mechanisms of Cd toxicity include oxidative stress and inflammation, recent studies have indicated that this metal can activate aryl hydrocarbon receptor (AHR) and exert effects on AHR-regulated genes (i.e. CYPs). AHR represents a link between environmental toxicants and immune response as high receptor expression is noted in immune cells and barrier tissues, thus the aim of presented study was to investigate if activation of AhR by Cd is associated with metals’ immunomodulatory effects. Treatment of lung leukocytes with Cd in vitro (non-toxic doses) caused an increase in mRNA levels for AHR, CYP1B1 and CYP1A1, but co-treatment with metal and AHR antagonist CH223191 indicated that higher Cd doses (5 and 10 μM) can activate CYPs directly while a lower dose (1 μM) exerted effects on CYPs expression through activation of AHR. Low Cd dose induced increased production of IL-6 and decreased TNF and IL-1β by lung leukocytes, compared to controls. Gene expression data revealed unchanged mRNA for IL-6, decreased TNF, but increased IL-1β. Lower IL-1β protein level despite increased mRNA, was a consequence of decreased mRNA for NLRP3, a component of inflammasome that is involved in processing of pro-IL-1β in IL-1β. All noted effects were abolished in the presence of CH223191. Data obtained indicate that immunomodulatory effects of low Cd dose are mediated through AHR activation.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches : abstract book
T1  - Environmentally relevant exposure to cadmium and health risks: involvement of aryl hydrocarbon receptor
SP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4794
ER  - 

@conference{
author = "Kulaš, Jelena and Tucović, Dina and Zeljković, Milica and Popović, Dušanka and Popov Aleksandrov, Aleksandra and Kataranovski, Milena and Mirkov, Ivana",
year = "2019",
abstract = "Cadmium (Cd) is a heavy metal widely spread in the environment and significant water and food contaminant. This metal exerts toxic effects in various tissues thus representing great threat to human health, and our previous study showed that oral consumption of Cd (in water for 30 days) increased the metal deposition and exerted immunomodulatory effects in lung leukocytes. Although the most studied mechanisms of Cd toxicity include oxidative stress and inflammation, recent studies have indicated that this metal can activate aryl hydrocarbon receptor (AHR) and exert effects on AHR-regulated genes (i.e. CYPs). AHR represents a link between environmental toxicants and immune response as high receptor expression is noted in immune cells and barrier tissues, thus the aim of presented study was to investigate if activation of AhR by Cd is associated with metals’ immunomodulatory effects. Treatment of lung leukocytes with Cd in vitro (non-toxic doses) caused an increase in mRNA levels for AHR, CYP1B1 and CYP1A1, but co-treatment with metal and AHR antagonist CH223191 indicated that higher Cd doses (5 and 10 μM) can activate CYPs directly while a lower dose (1 μM) exerted effects on CYPs expression through activation of AHR. Low Cd dose induced increased production of IL-6 and decreased TNF and IL-1β by lung leukocytes, compared to controls. Gene expression data revealed unchanged mRNA for IL-6, decreased TNF, but increased IL-1β. Lower IL-1β protein level despite increased mRNA, was a consequence of decreased mRNA for NLRP3, a component of inflammasome that is involved in processing of pro-IL-1β in IL-1β. All noted effects were abolished in the presence of CH223191. Data obtained indicate that immunomodulatory effects of low Cd dose are mediated through AHR activation.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches : abstract book",
title = "Environmentally relevant exposure to cadmium and health risks: involvement of aryl hydrocarbon receptor",
pages = "80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4794"
}

Kulaš, J., Tucović, D., Zeljković, M., Popović, D., Popov Aleksandrov, A., Kataranovski, M.,& Mirkov, I.. (2019). Environmentally relevant exposure to cadmium and health risks: involvement of aryl hydrocarbon receptor. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 80.
https://hdl.handle.net/21.15107/rcub_ibiss_4794

Kulaš J, Tucović D, Zeljković M, Popović D, Popov Aleksandrov A, Kataranovski M, Mirkov I. Environmentally relevant exposure to cadmium and health risks: involvement of aryl hydrocarbon receptor. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book. 2019;:80.
https://hdl.handle.net/21.15107/rcub_ibiss_4794 .

Kulaš, Jelena, Tucović, Dina, Zeljković, Milica, Popović, Dušanka, Popov Aleksandrov, Aleksandra, Kataranovski, Milena, Mirkov, Ivana, "Environmentally relevant exposure to cadmium and health risks: involvement of aryl hydrocarbon receptor" in Immunology at the Confluence of Multidisciplinary Approaches : abstract book (2019):80,
https://hdl.handle.net/21.15107/rcub_ibiss_4794 .

TY  - CONF
AU  - Tucović, Dina
AU  - Mirkov, Ivana
AU  - Kulaš, Jelena
AU  - Zeljković, Milica
AU  - Popović, Dušanka
AU  - Zolotarevski, Lidija
AU  - Đurđić, Slađana
AU  - Mutić, Jelena
AU  - Kataranovski, Milena
AU  - Popov Aleksandrov, Aleksandra
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4795
AB  - Adverse effects of non-occupational exposure to cadmium (Cd) are increasingly
acknowledged. Using a rat model of oral Cd exposure in drinking water we have shown
that skin is a target for this metal. Due to contribution of individual variability to the
intensity of cadmium toxicity, dermatotoxicity of two environmentally relevant Cd
doses (5 and 50 ppm) was examined in individuals of two rat strains, Albino Oxford
(AO) and Dark Agouti (DA), which differ in response to chemicals. A dose-dependent
accumulation of Cd in the skin/epidermal cells was noted in both strains, and although
there were no strain differences in the Cd accumulation, the degree of skin response to
the metal differed. Signs of skin damage were evident in both strains, but response to
injury was more pronounced in DA. Individuals of DA rats responded by an increase
in the levels of antioxidant defense enzymes in the skin already at lower dose, in
contrast to AO (which reacted to higher dose solely), implying higher sensitivity of DA
strain to Cd-induced toxicity. Epidermal cells from both strains developed stress
response, however increased GSH, and higher metallothionein/MT-1 and MT-2
mRNA, Nrf2 protein, apoptosis, Ahr and Cyp genes in AO, depicting this strain`s
ability to better defend against Cd insult. Epidermal cells` IL-1β, TNF and IL-6
response was induced by Cd in DA, while pro-inflammatory cytokine production was
unchanged in AO (though increased following stimulation with S. epidermidis), with
increased IL-10 as a possible underlying mechanism. T cells from non-exposed rats
produce more IFN-γ and IL-17 in co-culture with epidermal cell from Cd–exposed DA
rats what strengthens the view that this strain is more prone to metal’s dermatotoxicity.
These data give a new insight into repercussion of genetic variability to toxicity of
cadmium acquired by the skin via gut, bearing relevance for variations in the link
between dietary cadmium and inflammation-based skin pathologies.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches : abstract book
T1  - Environmentally relevant exposure to cadmium and health risks: skin as target organ
SP  - 79
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4795
ER  - 

@conference{
author = "Tucović, Dina and Mirkov, Ivana and Kulaš, Jelena and Zeljković, Milica and Popović, Dušanka and Zolotarevski, Lidija and Đurđić, Slađana and Mutić, Jelena and Kataranovski, Milena and Popov Aleksandrov, Aleksandra",
year = "2019",
abstract = "Adverse effects of non-occupational exposure to cadmium (Cd) are increasingly
acknowledged. Using a rat model of oral Cd exposure in drinking water we have shown
that skin is a target for this metal. Due to contribution of individual variability to the
intensity of cadmium toxicity, dermatotoxicity of two environmentally relevant Cd
doses (5 and 50 ppm) was examined in individuals of two rat strains, Albino Oxford
(AO) and Dark Agouti (DA), which differ in response to chemicals. A dose-dependent
accumulation of Cd in the skin/epidermal cells was noted in both strains, and although
there were no strain differences in the Cd accumulation, the degree of skin response to
the metal differed. Signs of skin damage were evident in both strains, but response to
injury was more pronounced in DA. Individuals of DA rats responded by an increase
in the levels of antioxidant defense enzymes in the skin already at lower dose, in
contrast to AO (which reacted to higher dose solely), implying higher sensitivity of DA
strain to Cd-induced toxicity. Epidermal cells from both strains developed stress
response, however increased GSH, and higher metallothionein/MT-1 and MT-2
mRNA, Nrf2 protein, apoptosis, Ahr and Cyp genes in AO, depicting this strain`s
ability to better defend against Cd insult. Epidermal cells` IL-1β, TNF and IL-6
response was induced by Cd in DA, while pro-inflammatory cytokine production was
unchanged in AO (though increased following stimulation with S. epidermidis), with
increased IL-10 as a possible underlying mechanism. T cells from non-exposed rats
produce more IFN-γ and IL-17 in co-culture with epidermal cell from Cd–exposed DA
rats what strengthens the view that this strain is more prone to metal’s dermatotoxicity.
These data give a new insight into repercussion of genetic variability to toxicity of
cadmium acquired by the skin via gut, bearing relevance for variations in the link
between dietary cadmium and inflammation-based skin pathologies.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches : abstract book",
title = "Environmentally relevant exposure to cadmium and health risks: skin as target organ",
pages = "79",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4795"
}

Tucović, D., Mirkov, I., Kulaš, J., Zeljković, M., Popović, D., Zolotarevski, L., Đurđić, S., Mutić, J., Kataranovski, M.,& Popov Aleksandrov, A.. (2019). Environmentally relevant exposure to cadmium and health risks: skin as target organ. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 79.
https://hdl.handle.net/21.15107/rcub_ibiss_4795

Tucović D, Mirkov I, Kulaš J, Zeljković M, Popović D, Zolotarevski L, Đurđić S, Mutić J, Kataranovski M, Popov Aleksandrov A. Environmentally relevant exposure to cadmium and health risks: skin as target organ. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book. 2019;:79.
https://hdl.handle.net/21.15107/rcub_ibiss_4795 .

Tucović, Dina, Mirkov, Ivana, Kulaš, Jelena, Zeljković, Milica, Popović, Dušanka, Zolotarevski, Lidija, Đurđić, Slađana, Mutić, Jelena, Kataranovski, Milena, Popov Aleksandrov, Aleksandra, "Environmentally relevant exposure to cadmium and health risks: skin as target organ" in Immunology at the Confluence of Multidisciplinary Approaches : abstract book (2019):79,
https://hdl.handle.net/21.15107/rcub_ibiss_4795 .

TY  - CONF
AU  - Marković, Milan
AU  - Marković, Katarina
AU  - Mirkov, Ivana
AU  - Tucović, Dina
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Popov Aleksandrov, Aleksandra
PY  - 2019
UR  - https://www.isos.rs/congress2019-abstract-book
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3580
UR  - https://radar.ibiss.bg.ac.rs/handle/handle/123456789/3558
AB  - Cadmium (Cd) is one of the most cytotoxic agents and environmental contaminants, which can cause serial health problems in various organs such as liver, kidney, testis, bone, nervous tissue and immune system. Furthermore, Cd is classified as a human and animal carcinogen agent. Despite the fact that Cd accumulates in the skin, there is a lack of evidence about its involvement in skin cancer biology. Skin cancer is one of the most common cancers worldwide, with melanoma as the most lethal type. Based on that, we set up the study to examine the effect of cadmium on the B16 melanoma cell line, measuring viability by MTT and crystal violet (CV) tests, proliferation rate (CFSE), ROS production (DHR), migration (scratch test) and adhesion on matrigel. The results showed that non-cytotoxic doses of cadmium (ranging from 0,3-2,5µM) increased viability, proliferation, and migration of B16 cells, while at the same time slightly promoted ROS production. Otherwise, pronounced oxidative stress induced by higher doses (ranging from 5-20µM) led to cell death. Summary, these results showed that low doses of cadmium could upregulate B16 melanoma cell line growth and migration probably through moderate ROS/RNS generation and thus their ability to modulate relevant signaling pathways involved in cancer progression. Considering that, underlying mechanisms of Cd impact on melanoma cell lines proliferation, migration and invasiveness needs to be clarified in vitro, as well as its relevance for in vivo system.
PB  - Belgrade: University of Belgrade Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia
PB  - Belgrade: Immunological Society of Serbia
C3  - Saksida T, Stanisavljević S, Miljković Đ, editors. Immunology at the Confluence of Multidisciplinary Approaches : abstract book; 2019 Dec 6-8; Belgrade, Serbia
T1  - Effect of non-cytotoxic doses of cadmium on the B16 melanoma cell line
SP  - 123
EP  - 123
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3580
ER  - 

@conference{
author = "Marković, Milan and Marković, Katarina and Mirkov, Ivana and Tucović, Dina and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Popov Aleksandrov, Aleksandra",
year = "2019",
abstract = "Cadmium (Cd) is one of the most cytotoxic agents and environmental contaminants, which can cause serial health problems in various organs such as liver, kidney, testis, bone, nervous tissue and immune system. Furthermore, Cd is classified as a human and animal carcinogen agent. Despite the fact that Cd accumulates in the skin, there is a lack of evidence about its involvement in skin cancer biology. Skin cancer is one of the most common cancers worldwide, with melanoma as the most lethal type. Based on that, we set up the study to examine the effect of cadmium on the B16 melanoma cell line, measuring viability by MTT and crystal violet (CV) tests, proliferation rate (CFSE), ROS production (DHR), migration (scratch test) and adhesion on matrigel. The results showed that non-cytotoxic doses of cadmium (ranging from 0,3-2,5µM) increased viability, proliferation, and migration of B16 cells, while at the same time slightly promoted ROS production. Otherwise, pronounced oxidative stress induced by higher doses (ranging from 5-20µM) led to cell death. Summary, these results showed that low doses of cadmium could upregulate B16 melanoma cell line growth and migration probably through moderate ROS/RNS generation and thus their ability to modulate relevant signaling pathways involved in cancer progression. Considering that, underlying mechanisms of Cd impact on melanoma cell lines proliferation, migration and invasiveness needs to be clarified in vitro, as well as its relevance for in vivo system.",
publisher = "Belgrade: University of Belgrade Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia, Belgrade: Immunological Society of Serbia",
journal = "Saksida T, Stanisavljević S, Miljković Đ, editors. Immunology at the Confluence of Multidisciplinary Approaches : abstract book; 2019 Dec 6-8; Belgrade, Serbia",
title = "Effect of non-cytotoxic doses of cadmium on the B16 melanoma cell line",
pages = "123-123",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3580"
}

Marković, M., Marković, K., Mirkov, I., Tucović, D., Mijatović, S., Maksimović-Ivanić, D.,& Popov Aleksandrov, A.. (2019). Effect of non-cytotoxic doses of cadmium on the B16 melanoma cell line. in Saksida T, Stanisavljević S, Miljković Đ, editors. Immunology at the Confluence of Multidisciplinary Approaches : abstract book; 2019 Dec 6-8; Belgrade, Serbia
Belgrade: University of Belgrade Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia., 123-123.
https://hdl.handle.net/21.15107/rcub_ibiss_3580

Marković M, Marković K, Mirkov I, Tucović D, Mijatović S, Maksimović-Ivanić D, Popov Aleksandrov A. Effect of non-cytotoxic doses of cadmium on the B16 melanoma cell line. in Saksida T, Stanisavljević S, Miljković Đ, editors. Immunology at the Confluence of Multidisciplinary Approaches : abstract book; 2019 Dec 6-8; Belgrade, Serbia. 2019;:123-123.
https://hdl.handle.net/21.15107/rcub_ibiss_3580 .

Marković, Milan, Marković, Katarina, Mirkov, Ivana, Tucović, Dina, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Popov Aleksandrov, Aleksandra, "Effect of non-cytotoxic doses of cadmium on the B16 melanoma cell line" in Saksida T, Stanisavljević S, Miljković Đ, editors. Immunology at the Confluence of Multidisciplinary Approaches : abstract book; 2019 Dec 6-8; Belgrade, Serbia (2019):123-123,
https://hdl.handle.net/21.15107/rcub_ibiss_3580 .

TY  - JOUR
AU  - Kulaš, Jelena
AU  - Mirkov, Ivana
AU  - Tucović, Dina
AU  - Zolotarevski, Lidija
AU  - Glamočlija, Jasmina
AU  - Veljović, Katarina
AU  - Tolinački, Maja
AU  - Golić, Nataša
AU  - Kataranovski, Milena
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0171298518301001?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3165
AB  - Microbiota inhabiting mucosal tissues is involved in maintenance of their immune homeostasis. Growing body of evidence indicate that dysbiosis in gut influence immune responses at distal sites including lungs. There are also reports concerning gut involvement with pulmonary injury/inflammation in settings of respiratory viral and bacterial infections. The impact of infections with other microorganisms on gut homeostasis is not explored. In this study, the rat model of sublethal pulmonary infection with Aspergillus fumigatus was used to investigate the effect of fungal respiratory infection on gut immune-mediated homeostasis. Signs of intestinal damage, intestinal and gut-draining lymphoid tissue cytokine responses and gut bacterial microbiota diversity were examined. Intestinal injury, inflammatory cell infiltration, as well as increased levels of intestinal interferon-γ (IFN-γ) and interleukin-17 (IL-17) (as opposed to unchanged levels of anti-inflammatory cytokine IL-10) during the two-week period depict intestinal inflammation in rats with pulmonary A. fumigatus infection. It could not be ascribed to the fungus as it was not detected in the intestine of infected rats. Increased production of pro-inflammatory cytokines by major gut-draining mesenteric lymph nodes point to these lymphoid organs as places of generation of cytokine-producing cells. No changes in spleen or systemic cytokine responses was observed, showing lack of the effects of pulmonary A. fumigatus infection outside mucosal immune system. Drop of intestinal bacterial microbiota diversity (disappearance of several bacterial bands) was noted early in infection with normalization starting from day seven. From day three, appearance of new bacterial bands (unique to infected individuals, not present in controls) was seen, and some of them are pathogens. Alterations in intestinal bacterial community might have affected intestinal immune tolerance contributing to inflammation. Disruption of gut homeostasis during pulmonary infection might render gastrointestinal tract more susceptible to variety of physiological and pathological stimuli. Data which showed for the first time gut involvement with pulmonary infection with A. fumigatus provide the baseline for future studies of the impact of fungal lung infections to gut homeostasis, particularly in individuals susceptible to these infections.
T2  - Immunobiology
T2  - Immunobiology
T1  - Pulmonary Aspergillus fumigatus infection in rats affects gastrointestinal homeostasis.
IS  - 1
VL  - 224
DO  - 10.1016/j.imbio.2018.10.001
SP  - 116
EP  - 123
ER  - 

@article{
author = "Kulaš, Jelena and Mirkov, Ivana and Tucović, Dina and Zolotarevski, Lidija and Glamočlija, Jasmina and Veljović, Katarina and Tolinački, Maja and Golić, Nataša and Kataranovski, Milena",
year = "2019",
abstract = "Microbiota inhabiting mucosal tissues is involved in maintenance of their immune homeostasis. Growing body of evidence indicate that dysbiosis in gut influence immune responses at distal sites including lungs. There are also reports concerning gut involvement with pulmonary injury/inflammation in settings of respiratory viral and bacterial infections. The impact of infections with other microorganisms on gut homeostasis is not explored. In this study, the rat model of sublethal pulmonary infection with Aspergillus fumigatus was used to investigate the effect of fungal respiratory infection on gut immune-mediated homeostasis. Signs of intestinal damage, intestinal and gut-draining lymphoid tissue cytokine responses and gut bacterial microbiota diversity were examined. Intestinal injury, inflammatory cell infiltration, as well as increased levels of intestinal interferon-γ (IFN-γ) and interleukin-17 (IL-17) (as opposed to unchanged levels of anti-inflammatory cytokine IL-10) during the two-week period depict intestinal inflammation in rats with pulmonary A. fumigatus infection. It could not be ascribed to the fungus as it was not detected in the intestine of infected rats. Increased production of pro-inflammatory cytokines by major gut-draining mesenteric lymph nodes point to these lymphoid organs as places of generation of cytokine-producing cells. No changes in spleen or systemic cytokine responses was observed, showing lack of the effects of pulmonary A. fumigatus infection outside mucosal immune system. Drop of intestinal bacterial microbiota diversity (disappearance of several bacterial bands) was noted early in infection with normalization starting from day seven. From day three, appearance of new bacterial bands (unique to infected individuals, not present in controls) was seen, and some of them are pathogens. Alterations in intestinal bacterial community might have affected intestinal immune tolerance contributing to inflammation. Disruption of gut homeostasis during pulmonary infection might render gastrointestinal tract more susceptible to variety of physiological and pathological stimuli. Data which showed for the first time gut involvement with pulmonary infection with A. fumigatus provide the baseline for future studies of the impact of fungal lung infections to gut homeostasis, particularly in individuals susceptible to these infections.",
journal = "Immunobiology, Immunobiology",
title = "Pulmonary Aspergillus fumigatus infection in rats affects gastrointestinal homeostasis.",
number = "1",
volume = "224",
doi = "10.1016/j.imbio.2018.10.001",
pages = "116-123"
}

Kulaš, J., Mirkov, I., Tucović, D., Zolotarevski, L., Glamočlija, J., Veljović, K., Tolinački, M., Golić, N.,& Kataranovski, M.. (2019). Pulmonary Aspergillus fumigatus infection in rats affects gastrointestinal homeostasis.. in Immunobiology, 224(1), 116-123.
https://doi.org/10.1016/j.imbio.2018.10.001

Kulaš J, Mirkov I, Tucović D, Zolotarevski L, Glamočlija J, Veljović K, Tolinački M, Golić N, Kataranovski M. Pulmonary Aspergillus fumigatus infection in rats affects gastrointestinal homeostasis.. in Immunobiology. 2019;224(1):116-123.
doi:10.1016/j.imbio.2018.10.001 .

Kulaš, Jelena, Mirkov, Ivana, Tucović, Dina, Zolotarevski, Lidija, Glamočlija, Jasmina, Veljović, Katarina, Tolinački, Maja, Golić, Nataša, Kataranovski, Milena, "Pulmonary Aspergillus fumigatus infection in rats affects gastrointestinal homeostasis." in Immunobiology, 224, no. 1 (2019):116-123,
https://doi.org/10.1016/j.imbio.2018.10.001 . .

TY  - JOUR
AU  - Kulaš, Jelena
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Popov Aleksandrov, Aleksandra
AU  - Ukropina, Mirela
AU  - Cakić Milošević, Maja
AU  - Mutić, Jelena
AU  - Kataranovski, Milena
AU  - Mirkov, Ivana
PY  - 2019
UR  - http://www.besjournal.com/en/article/doi/10.3967/bes2019.068
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3470
AB  - OBJECTIVE The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. METHODS Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1β, IL-6, IL-10, and IL-17] were investigated. RESULTS Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. CONCLUSION The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.
PB  - Biomedical and Environmental Sciences
T2  - Biomedical and Environmental Sciences
T1  - Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.
IS  - 7
VL  - 32
DO  - 10.3967/bes2019.068
SP  - 508
EP  - 519
ER  - 

@article{
author = "Kulaš, Jelena and Ninkov, Marina and Tucović, Dina and Popov Aleksandrov, Aleksandra and Ukropina, Mirela and Cakić Milošević, Maja and Mutić, Jelena and Kataranovski, Milena and Mirkov, Ivana",
year = "2019",
abstract = "OBJECTIVE The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. METHODS Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1β, IL-6, IL-10, and IL-17] were investigated. RESULTS Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. CONCLUSION The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.",
publisher = "Biomedical and Environmental Sciences",
journal = "Biomedical and Environmental Sciences",
title = "Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.",
number = "7",
volume = "32",
doi = "10.3967/bes2019.068",
pages = "508-519"
}

Kulaš, J., Ninkov, M., Tucović, D., Popov Aleksandrov, A., Ukropina, M., Cakić Milošević, M., Mutić, J., Kataranovski, M.,& Mirkov, I.. (2019). Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.. in Biomedical and Environmental Sciences
Biomedical and Environmental Sciences., 32(7), 508-519.
https://doi.org/10.3967/bes2019.068

Kulaš J, Ninkov M, Tucović D, Popov Aleksandrov A, Ukropina M, Cakić Milošević M, Mutić J, Kataranovski M, Mirkov I. Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.. in Biomedical and Environmental Sciences. 2019;32(7):508-519.
doi:10.3967/bes2019.068 .

Kulaš, Jelena, Ninkov, Marina, Tucović, Dina, Popov Aleksandrov, Aleksandra, Ukropina, Mirela, Cakić Milošević, Maja, Mutić, Jelena, Kataranovski, Milena, Mirkov, Ivana, "Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats." in Biomedical and Environmental Sciences, 32, no. 7 (2019):508-519,
https://doi.org/10.3967/bes2019.068 . .

TY  - CONF
AU  - Mileusnić, Dina
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Kulaš, Jelena
AU  - Vukojević, Vesna
AU  - Đurđić, Slađana
AU  - Mutić, Jelena
AU  - Kataranovski, Milena
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4855
AB  - Epidemiological studies indicate a possible link between cadmium (Cd) ingested through food and various pathologies / diseases. There is no such data when it comes to skin, although the deposition of this metal in hair is used as a biomarker of human exposure. Only one study has shown the effect of orally administered Cd on wound healing, but the effects on other homeostatic skin activities, including immune, have not been investigated. In order to investigate the potential immunomodulatory effect of this heavy metal on the skin, DA strain rats were exposed to subchronic (30 days) oral intake of cadmium (in drinking water, 5 mg / l and 50 mg / l).Cd was deposited in this tissue and led to oxidative stress, judging by the increase in antioxidant enzymes (SOD and CAT), structural changes in the skin, as well as the presence / activation of innate immune cells. Higher concentrations of deposited Cd in the epidermis compared to the dermis resulted in a stress response at the epidermal cell (EC) level, manifested by increased mRNA expression for metallothioneins (MT-1 and MT-2) and decreased GSH after a higher dose of CdThis metal also led to the manifestation of signs of inflammation, judging by the increased expression of mRNA for iNOS and IL-1β and the production of NO and IL-1β, at a lower dose, and mRNA and IL-6 and TNF protein product at a higher dose. On the other hand, Cd led to increased production of the regulatory cytokine IL-10 (at higher doses). Increased IL-17 production was observed in EC cultures isolated from the skin of rats exposed to 50 mg / l, while the amount of cytokine produced further increased in EC co-culture with lymph node lymphocytes after ConA stimulation (both doses).Cd present in the skin also increased the ability of the EC to respond to the application of the contact allergen DNCB, judging by the increase in IL-6 and TNF (at both doses), while IL-1β remained unchanged. The presented results show a generally proinflammatory effect of Cd on epidermal cells and indicate the potential of orally ingested Cd to modulate immune responses in the skin.
PB  - Belgrade: Immunological Society of Serbia
C3  - Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia
T1  - Oral cadmium intake affect skin immune ractivity
T1  - Oralni unos kadmijuma utiče na imunsku reaktivnost kože
SP  - 24
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4855
ER  - 

@conference{
author = "Mileusnić, Dina and Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Ninkov, Marina and Kulaš, Jelena and Vukojević, Vesna and Đurđić, Slađana and Mutić, Jelena and Kataranovski, Milena",
year = "2018",
abstract = "Epidemiological studies indicate a possible link between cadmium (Cd) ingested through food and various pathologies / diseases. There is no such data when it comes to skin, although the deposition of this metal in hair is used as a biomarker of human exposure. Only one study has shown the effect of orally administered Cd on wound healing, but the effects on other homeostatic skin activities, including immune, have not been investigated. In order to investigate the potential immunomodulatory effect of this heavy metal on the skin, DA strain rats were exposed to subchronic (30 days) oral intake of cadmium (in drinking water, 5 mg / l and 50 mg / l).Cd was deposited in this tissue and led to oxidative stress, judging by the increase in antioxidant enzymes (SOD and CAT), structural changes in the skin, as well as the presence / activation of innate immune cells. Higher concentrations of deposited Cd in the epidermis compared to the dermis resulted in a stress response at the epidermal cell (EC) level, manifested by increased mRNA expression for metallothioneins (MT-1 and MT-2) and decreased GSH after a higher dose of CdThis metal also led to the manifestation of signs of inflammation, judging by the increased expression of mRNA for iNOS and IL-1β and the production of NO and IL-1β, at a lower dose, and mRNA and IL-6 and TNF protein product at a higher dose. On the other hand, Cd led to increased production of the regulatory cytokine IL-10 (at higher doses). Increased IL-17 production was observed in EC cultures isolated from the skin of rats exposed to 50 mg / l, while the amount of cytokine produced further increased in EC co-culture with lymph node lymphocytes after ConA stimulation (both doses).Cd present in the skin also increased the ability of the EC to respond to the application of the contact allergen DNCB, judging by the increase in IL-6 and TNF (at both doses), while IL-1β remained unchanged. The presented results show a generally proinflammatory effect of Cd on epidermal cells and indicate the potential of orally ingested Cd to modulate immune responses in the skin.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia",
title = "Oral cadmium intake affect skin immune ractivity, Oralni unos kadmijuma utiče na imunsku reaktivnost kože",
pages = "24",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4855"
}

Mileusnić, D., Popov Aleksandrov, A., Mirkov, I., Ninkov, M., Kulaš, J., Vukojević, V., Đurđić, S., Mutić, J.,& Kataranovski, M.. (2018). Oral cadmium intake affect skin immune ractivity. in Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia
Belgrade: Immunological Society of Serbia., 24.
https://hdl.handle.net/21.15107/rcub_ibiss_4855

Mileusnić D, Popov Aleksandrov A, Mirkov I, Ninkov M, Kulaš J, Vukojević V, Đurđić S, Mutić J, Kataranovski M. Oral cadmium intake affect skin immune ractivity. in Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia. 2018;:24.
https://hdl.handle.net/21.15107/rcub_ibiss_4855 .

Mileusnić, Dina, Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Ninkov, Marina, Kulaš, Jelena, Vukojević, Vesna, Đurđić, Slađana, Mutić, Jelena, Kataranovski, Milena, "Oral cadmium intake affect skin immune ractivity" in Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia (2018):24,
https://hdl.handle.net/21.15107/rcub_ibiss_4855 .

TY  - JOUR
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Demenesku, Jelena
AU  - Subota, Vesna
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S027869151830019X?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2999
AB  - Warfarin is the world's most widely used anticoagulant drug. Its anticoagulant activity is based on the inhibition of the vitamin K-dependent (VKD) step in the complete synthesis of a number of blood coagulation factors that are required for normal blood coagulation. Warfarin also affects synthesis of VKD proteins not related to haemostasis including those involved in bone growth and vascular calcification. Antithrombotic activity of warfarin is considered responsible for some aspects of its anti-tumour activity of warfarin. Some aspects of activities against tumours seem not to be related to haemostasis and included effects of warfarin on non-haemostatic VKD proteins as well as those not related to VKD proteins. Inflammatory/immunomodulatory effects of warfarin indicate much broader potential of action of this drug both in physiological and pathological processes. This review provides an overview of the published data dealing with the effects of warfarin on biological processes other than haemostasis.
PB  - Pergamon
T2  - Food and Chemical Toxicology
T1  - Effects of warfarin on biological processes other than haemostasis: A review.
VL  - 113
DO  - 10.1016/j.fct.2018.01.019
SP  - 19
EP  - 32
ER  - 

@article{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Ninkov, Marina and Tucović, Dina and Demenesku, Jelena and Subota, Vesna and Kataranovski, Dragan and Kataranovski, Milena",
year = "2018",
abstract = "Warfarin is the world's most widely used anticoagulant drug. Its anticoagulant activity is based on the inhibition of the vitamin K-dependent (VKD) step in the complete synthesis of a number of blood coagulation factors that are required for normal blood coagulation. Warfarin also affects synthesis of VKD proteins not related to haemostasis including those involved in bone growth and vascular calcification. Antithrombotic activity of warfarin is considered responsible for some aspects of its anti-tumour activity of warfarin. Some aspects of activities against tumours seem not to be related to haemostasis and included effects of warfarin on non-haemostatic VKD proteins as well as those not related to VKD proteins. Inflammatory/immunomodulatory effects of warfarin indicate much broader potential of action of this drug both in physiological and pathological processes. This review provides an overview of the published data dealing with the effects of warfarin on biological processes other than haemostasis.",
publisher = "Pergamon",
journal = "Food and Chemical Toxicology",
title = "Effects of warfarin on biological processes other than haemostasis: A review.",
volume = "113",
doi = "10.1016/j.fct.2018.01.019",
pages = "19-32"
}

Popov Aleksandrov, A., Mirkov, I., Ninkov, M., Tucović, D., Demenesku, J., Subota, V., Kataranovski, D.,& Kataranovski, M.. (2018). Effects of warfarin on biological processes other than haemostasis: A review.. in Food and Chemical Toxicology
Pergamon., 113, 19-32.
https://doi.org/10.1016/j.fct.2018.01.019

Popov Aleksandrov A, Mirkov I, Ninkov M, Tucović D, Demenesku J, Subota V, Kataranovski D, Kataranovski M. Effects of warfarin on biological processes other than haemostasis: A review.. in Food and Chemical Toxicology. 2018;113:19-32.
doi:10.1016/j.fct.2018.01.019 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Ninkov, Marina, Tucović, Dina, Demenesku, Jelena, Subota, Vesna, Kataranovski, Dragan, Kataranovski, Milena, "Effects of warfarin on biological processes other than haemostasis: A review." in Food and Chemical Toxicology, 113 (2018):19-32,
https://doi.org/10.1016/j.fct.2018.01.019 . .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Subota, Vesna
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2018
UR  - http://doi.wiley.com/10.1111/1749-4877.12296
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29168613
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3021
AB  - Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage.
T2  - Integrative Zoology
T1  - Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.
IS  - 2
VL  - 13
DO  - 10.1111/1749-4877.12296
SP  - 180
EP  - 193
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Subota, Vesna and Kataranovski, Dragan and Kataranovski, Milena",
year = "2018",
abstract = "Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage.",
journal = "Integrative Zoology",
title = "Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.",
number = "2",
volume = "13",
doi = "10.1111/1749-4877.12296",
pages = "180-193"
}

Mirkov, I., Popov Aleksandrov, A., Subota, V., Kataranovski, D.,& Kataranovski, M.. (2018). Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.. in Integrative Zoology, 13(2), 180-193.
https://doi.org/10.1111/1749-4877.12296

Mirkov I, Popov Aleksandrov A, Subota V, Kataranovski D, Kataranovski M. Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.. in Integrative Zoology. 2018;13(2):180-193.
doi:10.1111/1749-4877.12296 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Subota, Vesna, Kataranovski, Dragan, Kataranovski, Milena, "Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation." in Integrative Zoology, 13, no. 2 (2018):180-193,
https://doi.org/10.1111/1749-4877.12296 . .

TY  - JOUR
AU  - Tucović, Dina
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Kulaš, Jelena
AU  - Zolotarevski, Lidija
AU  - Vukojević, Vesna
AU  - Mutić, Jelena
AU  - Tatalović, Nikola
AU  - Kataranovski, Milena
PY  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S0147651318307231?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3126
AB  - Skin can acquire cadmium (Cd) by oral route, but there is paucity of data concerning cutaneous effects of this metal. Cd acquired by oral route can affect skin wound healing, but the effect of Cd on other activities involved in skin homeostasis, including skin immunity, are not explored. Using the rat model of 30-day oral administration of Cd (5 ppm and 50 ppm) in drinking water, basic aspects of immune-relevant activity of epidermal cells were examined. Dose-dependent Cd deposition in the the skin was observed (0.035 ± 0.02 µg/g and 0.127 ± 0.04 µg/g at 5 ppm and 50 ppm, respectively, compared to 0.012 ± 0.009 µg/g at 0 ppm of Cd). This resulted in skin inflammation (oxidative stress at both Cd doses and dose-dependent structural changes in the skin and the presence/activation of innate immunity cells). At low Cd dose inflammatory response (nitric oxide and IL-1β) was observed. Other inflammatory cytokines (IL-6 and TNF) response occurred at 50 ppm, which was increased further following skin sensitization with contact allergen dinitro-chlorobenzene (DNCB). Epidermal cells exposed to both Cd doses enhanced concanavalin A (ConA)-stimulated lymphocyte production of IL-17. This study showed for the first time the effect of the metal which gained access to the skin via gut on immune reactivity of epidermal cells. Presented data might be relevant for the link between dietary Cd and the risk of skin pathologies.
T2  - Ecotoxicology and Environmental Safety
T1  - Oral cadmium exposure affects skin immune reactivity in rats.
VL  - 164
DO  - 10.1016/j.ecoenv.2018.07.117
SP  - 12
EP  - 20
ER  - 

@article{
author = "Tucović, Dina and Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Ninkov, Marina and Kulaš, Jelena and Zolotarevski, Lidija and Vukojević, Vesna and Mutić, Jelena and Tatalović, Nikola and Kataranovski, Milena",
year = "2018",
abstract = "Skin can acquire cadmium (Cd) by oral route, but there is paucity of data concerning cutaneous effects of this metal. Cd acquired by oral route can affect skin wound healing, but the effect of Cd on other activities involved in skin homeostasis, including skin immunity, are not explored. Using the rat model of 30-day oral administration of Cd (5 ppm and 50 ppm) in drinking water, basic aspects of immune-relevant activity of epidermal cells were examined. Dose-dependent Cd deposition in the the skin was observed (0.035 ± 0.02 µg/g and 0.127 ± 0.04 µg/g at 5 ppm and 50 ppm, respectively, compared to 0.012 ± 0.009 µg/g at 0 ppm of Cd). This resulted in skin inflammation (oxidative stress at both Cd doses and dose-dependent structural changes in the skin and the presence/activation of innate immunity cells). At low Cd dose inflammatory response (nitric oxide and IL-1β) was observed. Other inflammatory cytokines (IL-6 and TNF) response occurred at 50 ppm, which was increased further following skin sensitization with contact allergen dinitro-chlorobenzene (DNCB). Epidermal cells exposed to both Cd doses enhanced concanavalin A (ConA)-stimulated lymphocyte production of IL-17. This study showed for the first time the effect of the metal which gained access to the skin via gut on immune reactivity of epidermal cells. Presented data might be relevant for the link between dietary Cd and the risk of skin pathologies.",
journal = "Ecotoxicology and Environmental Safety",
title = "Oral cadmium exposure affects skin immune reactivity in rats.",
volume = "164",
doi = "10.1016/j.ecoenv.2018.07.117",
pages = "12-20"
}

Tucović, D., Popov Aleksandrov, A., Mirkov, I., Ninkov, M., Kulaš, J., Zolotarevski, L., Vukojević, V., Mutić, J., Tatalović, N.,& Kataranovski, M.. (2018). Oral cadmium exposure affects skin immune reactivity in rats.. in Ecotoxicology and Environmental Safety, 164, 12-20.
https://doi.org/10.1016/j.ecoenv.2018.07.117

Tucović D, Popov Aleksandrov A, Mirkov I, Ninkov M, Kulaš J, Zolotarevski L, Vukojević V, Mutić J, Tatalović N, Kataranovski M. Oral cadmium exposure affects skin immune reactivity in rats.. in Ecotoxicology and Environmental Safety. 2018;164:12-20.
doi:10.1016/j.ecoenv.2018.07.117 .

Tucović, Dina, Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Ninkov, Marina, Kulaš, Jelena, Zolotarevski, Lidija, Vukojević, Vesna, Mutić, Jelena, Tatalović, Nikola, Kataranovski, Milena, "Oral cadmium exposure affects skin immune reactivity in rats." in Ecotoxicology and Environmental Safety, 164 (2018):12-20,
https://doi.org/10.1016/j.ecoenv.2018.07.117 . .

TY  - JOUR
AU  - Janićijević, Željko
AU  - Ninkov, Marina
AU  - Kataranovski, Milena
AU  - Radovanović, Filip
PY  - 2018
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/mabi.201800322
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3219
AB  - Poly(DL-lactide-co-ε-caprolactone)/poly(acrylic acid) implantable composite reservoirs for cationic drugs are synthesized by sequentially applying photoirradiation and liquid phase inversion. The chemical composition and microstructure of reservoirs are characterized with Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) and scanning electron microscopy (SEM), respectively. Drug loading and release properties are investigated using methylene blue as the drug model. Biocompatibility of reservoirs is examined through a series of in vitro tests and an in vivo experiment of subcutaneous implantation in Dark Agouti rats. Reservoirs show good ion-exchange capacity, high water content, and fast reversible swelling with retained geometry. Results of drug loading and release reveal excellent loading efficiency and diffusion-controlled release during 2 weeks. Biocompatibility tests in vitro demonstrate the lack of implant proinflammatory potential and hindered adhesion of L929 cells on the implant surface. Implants exhibit low acute toxicity and elicit a normal acute foreign body reaction that reaches the early stages of fibrous capsule formation after 7 days.
T2  - Macromolecular Bioscience
T1  - Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs.
DO  - 10.1002/mabi.201800322
ER  - 

@article{
author = "Janićijević, Željko and Ninkov, Marina and Kataranovski, Milena and Radovanović, Filip",
year = "2018",
abstract = "Poly(DL-lactide-co-ε-caprolactone)/poly(acrylic acid) implantable composite reservoirs for cationic drugs are synthesized by sequentially applying photoirradiation and liquid phase inversion. The chemical composition and microstructure of reservoirs are characterized with Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) and scanning electron microscopy (SEM), respectively. Drug loading and release properties are investigated using methylene blue as the drug model. Biocompatibility of reservoirs is examined through a series of in vitro tests and an in vivo experiment of subcutaneous implantation in Dark Agouti rats. Reservoirs show good ion-exchange capacity, high water content, and fast reversible swelling with retained geometry. Results of drug loading and release reveal excellent loading efficiency and diffusion-controlled release during 2 weeks. Biocompatibility tests in vitro demonstrate the lack of implant proinflammatory potential and hindered adhesion of L929 cells on the implant surface. Implants exhibit low acute toxicity and elicit a normal acute foreign body reaction that reaches the early stages of fibrous capsule formation after 7 days.",
journal = "Macromolecular Bioscience",
title = "Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs.",
doi = "10.1002/mabi.201800322"
}

Janićijević, Ž., Ninkov, M., Kataranovski, M.,& Radovanović, F.. (2018). Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs.. in Macromolecular Bioscience.
https://doi.org/10.1002/mabi.201800322

Janićijević Ž, Ninkov M, Kataranovski M, Radovanović F. Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs.. in Macromolecular Bioscience. 2018;.
doi:10.1002/mabi.201800322 .

Janićijević, Željko, Ninkov, Marina, Kataranovski, Milena, Radovanović, Filip, "Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs." in Macromolecular Bioscience (2018),
https://doi.org/10.1002/mabi.201800322 . .

TY  - CONF
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Kulaš, Jelena
AU  - Jovčić, Jelena
AU  - Stefanović, Jana
AU  - Glamočlija, Jasmina
AU  - Veljović, Katarina
AU  - Kataranovski, Milena
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4856
AB  - Our previous studies have shown poorer activity / absence of cellular immune response in AO compared to DA rats. Given the scarcity of data on innate immunity reactions in these two strains, the aim of this study was to obtain initial data on this type of immune activity. Using a model of subcutaneously implanted polyvinyl sponges, the basic aspects of neutrophil leukocyte activity important for the response to A. fumigatus were examined.Although a higher number of neutrophil leukocytes of AO rats migrate to fungal-free sponges (group K), the yield of cells from fungal sponges (group A) is the same in both strains, while CD11b cell expression is lower in both AO groups compared to DA rats. . Despite the higher oxidative activity of cells from group AO compared to DA, NBT reduction is the same (spontaneous) or lower (after stimulation with PMA) in group A compared to K in AO, and the production of myeloperoxidase (MPO) and NO is lower .In DA rats, the presence of the fungus leads to an increase in the activity of A cells in relation to group K. Molecular identification of the bacterial composition of the lung microbiota under conditions of infection with A. fumigatus established the presence of Staphylococcus epidermidis and Veillonella cavie only in AO, and Streptococcus salivarius and Propionibacterium acne only in DA rats. The presence of different doses of S. epidermidis (SE) in the sponge with A led to inhibition of MPO production in both strains. Soybean differences were observed depending on the dose of SE and / or the test activity. The lowest dose leads to inhibition of NBT reduction in AO, but stimulation in DA, while higher doses of SE stimulate the response in both strains.The low concentration of the bacterium has no effect on the production of NO in AO, but higher doses stimulate it, in contrast to the inhibition in DA at all doses of SE. The presented results indicate the existence of strain differences in the innate-immune response of rats, as well as that they may depend on the type of activity examined.
PB  - Belgrade: Immunological Society of Serbia
C3  - Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia
T1  - Influence of strain on the innate-immune reactions in rats
T1  - Uticaj soja na urođeno-imunske reakcije pacova
SP  - 18
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4856
ER  - 

@conference{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Mileusnić, Dina and Kulaš, Jelena and Jovčić, Jelena and Stefanović, Jana and Glamočlija, Jasmina and Veljović, Katarina and Kataranovski, Milena",
year = "2017",
abstract = "Our previous studies have shown poorer activity / absence of cellular immune response in AO compared to DA rats. Given the scarcity of data on innate immunity reactions in these two strains, the aim of this study was to obtain initial data on this type of immune activity. Using a model of subcutaneously implanted polyvinyl sponges, the basic aspects of neutrophil leukocyte activity important for the response to A. fumigatus were examined.Although a higher number of neutrophil leukocytes of AO rats migrate to fungal-free sponges (group K), the yield of cells from fungal sponges (group A) is the same in both strains, while CD11b cell expression is lower in both AO groups compared to DA rats. . Despite the higher oxidative activity of cells from group AO compared to DA, NBT reduction is the same (spontaneous) or lower (after stimulation with PMA) in group A compared to K in AO, and the production of myeloperoxidase (MPO) and NO is lower .In DA rats, the presence of the fungus leads to an increase in the activity of A cells in relation to group K. Molecular identification of the bacterial composition of the lung microbiota under conditions of infection with A. fumigatus established the presence of Staphylococcus epidermidis and Veillonella cavie only in AO, and Streptococcus salivarius and Propionibacterium acne only in DA rats. The presence of different doses of S. epidermidis (SE) in the sponge with A led to inhibition of MPO production in both strains. Soybean differences were observed depending on the dose of SE and / or the test activity. The lowest dose leads to inhibition of NBT reduction in AO, but stimulation in DA, while higher doses of SE stimulate the response in both strains.The low concentration of the bacterium has no effect on the production of NO in AO, but higher doses stimulate it, in contrast to the inhibition in DA at all doses of SE. The presented results indicate the existence of strain differences in the innate-immune response of rats, as well as that they may depend on the type of activity examined.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia",
title = "Influence of strain on the innate-immune reactions in rats, Uticaj soja na urođeno-imunske reakcije pacova",
pages = "18",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4856"
}

Mirkov, I., Popov Aleksandrov, A., Ninkov, M., Mileusnić, D., Kulaš, J., Jovčić, J., Stefanović, J., Glamočlija, J., Veljović, K.,& Kataranovski, M.. (2017). Influence of strain on the innate-immune reactions in rats. in Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia
Belgrade: Immunological Society of Serbia., 18.
https://hdl.handle.net/21.15107/rcub_ibiss_4856

Mirkov I, Popov Aleksandrov A, Ninkov M, Mileusnić D, Kulaš J, Jovčić J, Stefanović J, Glamočlija J, Veljović K, Kataranovski M. Influence of strain on the innate-immune reactions in rats. in Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia. 2017;:18.
https://hdl.handle.net/21.15107/rcub_ibiss_4856 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Mileusnić, Dina, Kulaš, Jelena, Jovčić, Jelena, Stefanović, Jana, Glamočlija, Jasmina, Veljović, Katarina, Kataranovski, Milena, "Influence of strain on the innate-immune reactions in rats" in Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia (2017):18,
https://hdl.handle.net/21.15107/rcub_ibiss_4856 .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2017
UR  - https://www.tandfonline.com/doi/full/10.1080/15569527.2016.1275664
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2555
AB  - Purpose: Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined. Materials and methods: Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation. Results: Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48+ cells) at days 1 and 3 post implantation and CD11b+ cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged. Conclusions: Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on inflammatory response to sponge implants might affect the course and/or duration of this reaction.
T2  - Cutaneous and Ocular Toxicology
T1  - Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats
DO  - 10.1080/15569527.2016.1275664
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Ninkov, Marina and Tucović, Dina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2017",
abstract = "Purpose: Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined. Materials and methods: Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation. Results: Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48+ cells) at days 1 and 3 post implantation and CD11b+ cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged. Conclusions: Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on inflammatory response to sponge implants might affect the course and/or duration of this reaction.",
journal = "Cutaneous and Ocular Toxicology",
title = "Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats",
doi = "10.1080/15569527.2016.1275664"
}

Mirkov, I., Popov Aleksandrov, A., Demenesku, J., Ninkov, M., Tucović, D., Kataranovski, D.,& Kataranovski, M.. (2017). Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats. in Cutaneous and Ocular Toxicology.
https://doi.org/10.1080/15569527.2016.1275664

Mirkov I, Popov Aleksandrov A, Demenesku J, Ninkov M, Tucović D, Kataranovski D, Kataranovski M. Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats. in Cutaneous and Ocular Toxicology. 2017;.
doi:10.1080/15569527.2016.1275664 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Ninkov, Marina, Tucović, Dina, Kataranovski, Dragan, Kataranovski, Milena, "Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats" in Cutaneous and Ocular Toxicology (2017),
https://doi.org/10.1080/15569527.2016.1275664 . .

TY  - JOUR
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Zolotarevski, Lidija
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2017
UR  - https://www.sciencedirect.com/science/article/pii/S1382668917301746?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3540
AB  - Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity.
T2  - Environmental Toxicology and Pharmacology
T1  - Oral warfarin intake affects skin inflammatory cytokine responses in rats.
VL  - 54
DO  - 10.1016/j.etap.2017.06.027
SP  - 93
EP  - 98
ER  - 

@article{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Zolotarevski, Lidija and Ninkov, Marina and Tucović, Dina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2017",
abstract = "Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity.",
journal = "Environmental Toxicology and Pharmacology",
title = "Oral warfarin intake affects skin inflammatory cytokine responses in rats.",
volume = "54",
doi = "10.1016/j.etap.2017.06.027",
pages = "93-98"
}

Popov Aleksandrov, A., Mirkov, I., Zolotarevski, L., Ninkov, M., Tucović, D., Kataranovski, D.,& Kataranovski, M.. (2017). Oral warfarin intake affects skin inflammatory cytokine responses in rats.. in Environmental Toxicology and Pharmacology, 54, 93-98.
https://doi.org/10.1016/j.etap.2017.06.027

Popov Aleksandrov A, Mirkov I, Zolotarevski L, Ninkov M, Tucović D, Kataranovski D, Kataranovski M. Oral warfarin intake affects skin inflammatory cytokine responses in rats.. in Environmental Toxicology and Pharmacology. 2017;54:93-98.
doi:10.1016/j.etap.2017.06.027 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Zolotarevski, Lidija, Ninkov, Marina, Tucović, Dina, Kataranovski, Dragan, Kataranovski, Milena, "Oral warfarin intake affects skin inflammatory cytokine responses in rats." in Environmental Toxicology and Pharmacology, 54 (2017):93-98,
https://doi.org/10.1016/j.etap.2017.06.027 . .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Demenesku, Jelena
AU  - Zolotarevski, Lidija
AU  - Subota, Vesna
AU  - Stefik, Debora
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4813
AB  - Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is amongadverse effects of therapy in humans. Having in mind genetic variations in the effectiveness ofWF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinaltoxicity of oral warfarin in rats were examined in this study. High WF dose (3.5 mg/l) led tomortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher valuesof prothrombin time were noted at low WF dose (0.35 mg/l) in the former strain. Leukocyteinfiltration in intestine noted at this dose in both strains was associated with oxidative injury andmore pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cellproliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats,represent different strategies to protect vulnerable intestine from harmful immune responses.
PB  - Amsterdam, Holland:Elsevier B.V.
T2  - Environmental Toxicology and Pharmacology
T1  - Strain differences in intestinal toxicity of warfarin in rats
VL  - 48
DO  - 10.1016/j.etap.2016.10.019
SP  - 175
EP  - 182
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Mileusnić, Dina and Demenesku, Jelena and Zolotarevski, Lidija and Subota, Vesna and Stefik, Debora and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is amongadverse effects of therapy in humans. Having in mind genetic variations in the effectiveness ofWF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinaltoxicity of oral warfarin in rats were examined in this study. High WF dose (3.5 mg/l) led tomortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher valuesof prothrombin time were noted at low WF dose (0.35 mg/l) in the former strain. Leukocyteinfiltration in intestine noted at this dose in both strains was associated with oxidative injury andmore pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cellproliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats,represent different strategies to protect vulnerable intestine from harmful immune responses.",
publisher = "Amsterdam, Holland:Elsevier B.V.",
journal = "Environmental Toxicology and Pharmacology",
title = "Strain differences in intestinal toxicity of warfarin in rats",
volume = "48",
doi = "10.1016/j.etap.2016.10.019",
pages = "175-182"
}

Mirkov, I., Popov Aleksandrov, A., Ninkov, M., Mileusnić, D., Demenesku, J., Zolotarevski, L., Subota, V., Stefik, D., Kataranovski, D.,& Kataranovski, M.. (2016). Strain differences in intestinal toxicity of warfarin in rats. in Environmental Toxicology and Pharmacology
Amsterdam, Holland:Elsevier B.V.., 48, 175-182.
https://doi.org/10.1016/j.etap.2016.10.019

Mirkov I, Popov Aleksandrov A, Ninkov M, Mileusnić D, Demenesku J, Zolotarevski L, Subota V, Stefik D, Kataranovski D, Kataranovski M. Strain differences in intestinal toxicity of warfarin in rats. in Environmental Toxicology and Pharmacology. 2016;48:175-182.
doi:10.1016/j.etap.2016.10.019 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Mileusnić, Dina, Demenesku, Jelena, Zolotarevski, Lidija, Subota, Vesna, Stefik, Debora, Kataranovski, Dragan, Kataranovski, Milena, "Strain differences in intestinal toxicity of warfarin in rats" in Environmental Toxicology and Pharmacology, 48 (2016):175-182,
https://doi.org/10.1016/j.etap.2016.10.019 . .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Demenesku, Jelena
AU  - Zolotarevski, Lidija
AU  - Subota, Vesna
AU  - Stefik, Debora
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4812
AB  - Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is among
adverse effects of therapy in humans. Having in mind genetic variations in the effectiveness of
WF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinal
toxicity of oral warfarin in rats were examined in this study. High WF dose (3.5 mg/l) led to
mortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher values
of prothrombin time were noted at low WF dose (0.35 mg/l) in the former strain. Leukocyte
infiltration in intestine noted at this dose in both strains was associated with oxidative injury and
more pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cell
proliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats,
represent different strategies to protect vulnerable intestine from harmful immune responses.
PB  - Amsterdam, Holland:Elsevier B.V.
T2  - Environmental Toxicology and Pharmacology
T1  - Strain differences in intestinal toxicity of warfarin in rats
VL  - 48
DO  - 10.1016/j.etap.2016.10.019
SP  - 175
EP  - 182
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Mileusnić, Dina and Demenesku, Jelena and Zolotarevski, Lidija and Subota, Vesna and Stefik, Debora and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is among
adverse effects of therapy in humans. Having in mind genetic variations in the effectiveness of
WF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinal
toxicity of oral warfarin in rats were examined in this study. High WF dose (3.5 mg/l) led to
mortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher values
of prothrombin time were noted at low WF dose (0.35 mg/l) in the former strain. Leukocyte
infiltration in intestine noted at this dose in both strains was associated with oxidative injury and
more pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cell
proliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats,
represent different strategies to protect vulnerable intestine from harmful immune responses.",
publisher = "Amsterdam, Holland:Elsevier B.V.",
journal = "Environmental Toxicology and Pharmacology",
title = "Strain differences in intestinal toxicity of warfarin in rats",
volume = "48",
doi = "10.1016/j.etap.2016.10.019",
pages = "175-182"
}

Mirkov, I., Popov Aleksandrov, A., Ninkov, M., Mileusnić, D., Demenesku, J., Zolotarevski, L., Subota, V., Stefik, D., Kataranovski, D.,& Kataranovski, M.. (2016). Strain differences in intestinal toxicity of warfarin in rats. in Environmental Toxicology and Pharmacology
Amsterdam, Holland:Elsevier B.V.., 48, 175-182.
https://doi.org/10.1016/j.etap.2016.10.019

Mirkov I, Popov Aleksandrov A, Ninkov M, Mileusnić D, Demenesku J, Zolotarevski L, Subota V, Stefik D, Kataranovski D, Kataranovski M. Strain differences in intestinal toxicity of warfarin in rats. in Environmental Toxicology and Pharmacology. 2016;48:175-182.
doi:10.1016/j.etap.2016.10.019 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Mileusnić, Dina, Demenesku, Jelena, Zolotarevski, Lidija, Subota, Vesna, Stefik, Debora, Kataranovski, Dragan, Kataranovski, Milena, "Strain differences in intestinal toxicity of warfarin in rats" in Environmental Toxicology and Pharmacology, 48 (2016):175-182,
https://doi.org/10.1016/j.etap.2016.10.019 . .

TY  - JOUR
AU  - Subota, Vesna
AU  - Mirkov, Ivana
AU  - Demenesku, Jelena
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4814
AB  - Occupational/accidental exposure data have showed hemorrhage as a result of transdermal exposure to
warfarin, however, other effects are not known. In the present study, the impact of epicutaneous application of 10 g or 100 g of warfarin (three times, once a day) on peripheral blood polymorphonuclear
(PMN) and mononuclear cells (PBMC) was examined in rats. Both doses resulted in prolongation of prothrombin time and changes in hematologic parameters. Increases in PMN intracellular myeloperoxidase
(MPO) activity were seen at higher warfarin dose and both doses resulted in higher percentages of granular CD11b+ cells. In contrast, a decrease in PMN TNF and IL-6 production (ELISA) and gene expression
(RT-PCR) was observed. Epicutaneous application of warfarin resulted in decreased numbers of PBMC,
higher numbers of mononuclear CD11b+ cells, but without effect on PMBC cytokine production. The data
obtained showed differential effects of transdermal exposure to warfarin depending on leukocyte type
and activity.
PB  - Amsterdam : Elsevier
T2  - Environmental Toxicology and Pharmacology
T1  - Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats
VL  - 41
DO  - 10.1016/j.etap.2015.12.006
SP  - 232
EP  - 240
ER  - 

@article{
author = "Subota, Vesna and Mirkov, Ivana and Demenesku, Jelena and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Mileusnić, Dina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Occupational/accidental exposure data have showed hemorrhage as a result of transdermal exposure to
warfarin, however, other effects are not known. In the present study, the impact of epicutaneous application of 10 g or 100 g of warfarin (three times, once a day) on peripheral blood polymorphonuclear
(PMN) and mononuclear cells (PBMC) was examined in rats. Both doses resulted in prolongation of prothrombin time and changes in hematologic parameters. Increases in PMN intracellular myeloperoxidase
(MPO) activity were seen at higher warfarin dose and both doses resulted in higher percentages of granular CD11b+ cells. In contrast, a decrease in PMN TNF and IL-6 production (ELISA) and gene expression
(RT-PCR) was observed. Epicutaneous application of warfarin resulted in decreased numbers of PBMC,
higher numbers of mononuclear CD11b+ cells, but without effect on PMBC cytokine production. The data
obtained showed differential effects of transdermal exposure to warfarin depending on leukocyte type
and activity.",
publisher = "Amsterdam : Elsevier",
journal = "Environmental Toxicology and Pharmacology",
title = "Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats",
volume = "41",
doi = "10.1016/j.etap.2015.12.006",
pages = "232-240"
}

Subota, V., Mirkov, I., Demenesku, J., Popov Aleksandrov, A., Ninkov, M., Mileusnić, D., Kataranovski, D.,& Kataranovski, M.. (2016). Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats. in Environmental Toxicology and Pharmacology
Amsterdam : Elsevier., 41, 232-240.
https://doi.org/10.1016/j.etap.2015.12.006

Subota V, Mirkov I, Demenesku J, Popov Aleksandrov A, Ninkov M, Mileusnić D, Kataranovski D, Kataranovski M. Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats. in Environmental Toxicology and Pharmacology. 2016;41:232-240.
doi:10.1016/j.etap.2015.12.006 .

Subota, Vesna, Mirkov, Ivana, Demenesku, Jelena, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Mileusnić, Dina, Kataranovski, Dragan, Kataranovski, Milena, "Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats" in Environmental Toxicology and Pharmacology, 41 (2016):232-240,
https://doi.org/10.1016/j.etap.2015.12.006 . .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Zolotarevski, Lidija
AU  - Subota, Vesna
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4815
AB  - Though warfarin is extensively used in the prevention and treatment of thromboembolic
processes in humans, adverse effects of warfarin therapy have been recognized. Intestinal
hemorrhage is one of the hazards of anticoagulant therapy, but the mechanisms of warfarin
toxicity are virtually unknown. In this work, the effects of 30 days oral warfarin (0.35 mg/l and
3.5 mg/l) intake on rat’s gut were examined. Both doses resulted in prolongation of prothrombin
time. Systemic effects of higher warfarin dose (increases in plasma AST, proteinuria, hematuria,
changes in peripheral blood hematological parameters) were seen. Warfarin intake resulted in
histologically evident tissue damage, leukocyte infiltration and intestinal inflammation [increases
in myeloperoxidase activity, malondialdehyde content, superoxide dismutase and catalase
activity, proinflammatory cytokine (IFN-γ, IL-17) concentrations in intestinal homogenates]. In
contrast, suppression of gut-draining mesenteric lymph node (MLN) cell activity [proliferation
responsiveness, production of IFN-γ and IL-17 to T lymphocyte mitogen Concanavalin A
stimulation] was noted. Inhibition of regulatory cytokine IL-10 production by MLN cells,
suggests commitment of MLN to the suppression of all inflammatory activities and creation of
the microenvironment which is non-permissive for induction of potentially harmful immune
response. These novel findings indicate the need of staying alert for (adverse) effects of warfarin
therapy.
PB  - Amsterdam : Elsevier
T2  - Food and Chemical Toxicology
T1  - Intestinal toxicity of oral warfarin intake in rats
VL  - 94
DO  - 10.1016/j.fct.2016.05.007
SP  - 11
EP  - 18
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Ninkov, Marina and Mileusnić, Dina and Zolotarevski, Lidija and Subota, Vesna and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Though warfarin is extensively used in the prevention and treatment of thromboembolic
processes in humans, adverse effects of warfarin therapy have been recognized. Intestinal
hemorrhage is one of the hazards of anticoagulant therapy, but the mechanisms of warfarin
toxicity are virtually unknown. In this work, the effects of 30 days oral warfarin (0.35 mg/l and
3.5 mg/l) intake on rat’s gut were examined. Both doses resulted in prolongation of prothrombin
time. Systemic effects of higher warfarin dose (increases in plasma AST, proteinuria, hematuria,
changes in peripheral blood hematological parameters) were seen. Warfarin intake resulted in
histologically evident tissue damage, leukocyte infiltration and intestinal inflammation [increases
in myeloperoxidase activity, malondialdehyde content, superoxide dismutase and catalase
activity, proinflammatory cytokine (IFN-γ, IL-17) concentrations in intestinal homogenates]. In
contrast, suppression of gut-draining mesenteric lymph node (MLN) cell activity [proliferation
responsiveness, production of IFN-γ and IL-17 to T lymphocyte mitogen Concanavalin A
stimulation] was noted. Inhibition of regulatory cytokine IL-10 production by MLN cells,
suggests commitment of MLN to the suppression of all inflammatory activities and creation of
the microenvironment which is non-permissive for induction of potentially harmful immune
response. These novel findings indicate the need of staying alert for (adverse) effects of warfarin
therapy.",
publisher = "Amsterdam : Elsevier",
journal = "Food and Chemical Toxicology",
title = "Intestinal toxicity of oral warfarin intake in rats",
volume = "94",
doi = "10.1016/j.fct.2016.05.007",
pages = "11-18"
}

Mirkov, I., Popov Aleksandrov, A., Demenesku, J., Ninkov, M., Mileusnić, D., Zolotarevski, L., Subota, V., Kataranovski, D.,& Kataranovski, M.. (2016). Intestinal toxicity of oral warfarin intake in rats. in Food and Chemical Toxicology
Amsterdam : Elsevier., 94, 11-18.
https://doi.org/10.1016/j.fct.2016.05.007

Mirkov I, Popov Aleksandrov A, Demenesku J, Ninkov M, Mileusnić D, Zolotarevski L, Subota V, Kataranovski D, Kataranovski M. Intestinal toxicity of oral warfarin intake in rats. in Food and Chemical Toxicology. 2016;94:11-18.
doi:10.1016/j.fct.2016.05.007 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Ninkov, Marina, Mileusnić, Dina, Zolotarevski, Lidija, Subota, Vesna, Kataranovski, Dragan, Kataranovski, Milena, "Intestinal toxicity of oral warfarin intake in rats" in Food and Chemical Toxicology, 94 (2016):11-18,
https://doi.org/10.1016/j.fct.2016.05.007 . .

TY  - CONF
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Demenesku, Jelena
AU  - Brceski, Ilija
AU  - Tolinacki, Maja
AU  - Jovanovic, Sofija
AU  - Mileusnić, Dina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4854
AB  - Our previous research showed a higher reactivity of DA (compared to AO rats) to antigens that cause skin and lung inflammatory reactions. In order to examine the effect of strains on the immune responses of other regions, the effect of oral (in drinking water, 30 days) intake of cadmium, a known food and water contaminant, on the intestinal immune response of AO and DA rats was analyzed. Despite similar amounts of cadmium deposited in the intestines of both strains, the reduction in Lactobacillus (important for maintaining immune homeostasis in the intestine) and tissue damage (histologically and according to the marker of tissue necrosis, HMGB-1) was more pronounced in DA rats.Changes, including the activity of antioxidant defense enzymes (superoxide dismutase and catalase), increased concentrations of IFN-γ and IL-17, and no changes in IL-10, which were detected in intestinal homogenates only in DA strains, indicate a more intense intestinal inflammatory reaction. compared to AO strain. The same concentrations of cadmium detected in the main draining (mesenteric) lymph nodes (MLC) led to the induction of mRNA for metal-binding redox proteins (metallothioneins, MT) only in DA rats. The presence of a proinflammatory cytokine response (protein products and mRNA) of MLC cells, detected predominantly in DA strains, indicates a more pronounced induction of cells that produce these cytokines.Increased cell proliferation and oxidative activity of MLC cells, as well as the number of CD68 +, NKG2D + and CD11b + cells only in DA rats, with a differential change in IL-10 (decrease in DA, increase in AO) emphasizes the inflammatory character of MLC rat microenvironment of this strain. The absence of similar changes in the spleen (at the same tissue load of cadmium as MLC) indicates the influence of damaged intestinal tissue on the activity of regional lymph nodes, and the more intense response of MLC DA soy reflects greater efforts to prevent systemic immune response to changes in intestinal homeostasis.
PB  - Belgrade: Immunological Society of Serbia
C3  - VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata
T1  - Differential strain impact on immune reactivity: insights from regional immune responses in rats
T1  - Diferencijalni uticaj soja na imunsku reaktivnost: uvid iz regionalnih imunskih odgovora kod pacova
SP  - 10
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4854
ER  - 

@conference{
author = "Ninkov, Marina and Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Demenesku, Jelena and Brceski, Ilija and Tolinacki, Maja and Jovanovic, Sofija and Mileusnić, Dina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Our previous research showed a higher reactivity of DA (compared to AO rats) to antigens that cause skin and lung inflammatory reactions. In order to examine the effect of strains on the immune responses of other regions, the effect of oral (in drinking water, 30 days) intake of cadmium, a known food and water contaminant, on the intestinal immune response of AO and DA rats was analyzed. Despite similar amounts of cadmium deposited in the intestines of both strains, the reduction in Lactobacillus (important for maintaining immune homeostasis in the intestine) and tissue damage (histologically and according to the marker of tissue necrosis, HMGB-1) was more pronounced in DA rats.Changes, including the activity of antioxidant defense enzymes (superoxide dismutase and catalase), increased concentrations of IFN-γ and IL-17, and no changes in IL-10, which were detected in intestinal homogenates only in DA strains, indicate a more intense intestinal inflammatory reaction. compared to AO strain. The same concentrations of cadmium detected in the main draining (mesenteric) lymph nodes (MLC) led to the induction of mRNA for metal-binding redox proteins (metallothioneins, MT) only in DA rats. The presence of a proinflammatory cytokine response (protein products and mRNA) of MLC cells, detected predominantly in DA strains, indicates a more pronounced induction of cells that produce these cytokines.Increased cell proliferation and oxidative activity of MLC cells, as well as the number of CD68 +, NKG2D + and CD11b + cells only in DA rats, with a differential change in IL-10 (decrease in DA, increase in AO) emphasizes the inflammatory character of MLC rat microenvironment of this strain. The absence of similar changes in the spleen (at the same tissue load of cadmium as MLC) indicates the influence of damaged intestinal tissue on the activity of regional lymph nodes, and the more intense response of MLC DA soy reflects greater efforts to prevent systemic immune response to changes in intestinal homeostasis.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata",
title = "Differential strain impact on immune reactivity: insights from regional immune responses in rats, Diferencijalni uticaj soja na imunsku reaktivnost: uvid iz regionalnih imunskih odgovora kod pacova",
pages = "10",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4854"
}

Ninkov, M., Popov Aleksandrov, A., Mirkov, I., Demenesku, J., Brceski, I., Tolinacki, M., Jovanovic, S., Mileusnić, D., Kataranovski, D.,& Kataranovski, M.. (2016). Differential strain impact on immune reactivity: insights from regional immune responses in rats. in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata
Belgrade: Immunological Society of Serbia., 10.
https://hdl.handle.net/21.15107/rcub_ibiss_4854

Ninkov M, Popov Aleksandrov A, Mirkov I, Demenesku J, Brceski I, Tolinacki M, Jovanovic S, Mileusnić D, Kataranovski D, Kataranovski M. Differential strain impact on immune reactivity: insights from regional immune responses in rats. in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata. 2016;:10.
https://hdl.handle.net/21.15107/rcub_ibiss_4854 .

Ninkov, Marina, Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Demenesku, Jelena, Brceski, Ilija, Tolinacki, Maja, Jovanovic, Sofija, Mileusnić, Dina, Kataranovski, Dragan, Kataranovski, Milena, "Differential strain impact on immune reactivity: insights from regional immune responses in rats" in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata (2016):10,
https://hdl.handle.net/21.15107/rcub_ibiss_4854 .

TY  - CONF
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Zolotarevski, Lidija
AU  - Subota, Vesna
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4853
AB  - Warfarin is an anticoagulant that is widely used in the prevention and treatment of thromboembolic disorders in humans. Numerous side effects of oral therapy with this agent are known, which has led to the recommendation for transdermal administration of this agent. This study examined the effect of oral warfarin consumption (0.35 mg / l and 3.5 mg / l in drinking water, 30 days) on the intestinal immune system in rats, as well as the systemic effect (on peripheral blood leukocytes) of epicutaneous administration of this agent. µg or 100 µg, once a day, for three days).The anticoagulant effect, determined on the basis of the increase in prothrombin time, was observed after oral consumption of both doses, as well as after epicutaneous application. Orally administered warfarin leads to histologically evident damage to intestinal tissue and inflammation (cellular infiltration, myeloperoxidase activity, malodialdehyde content and superoxide dismutase and catalase activities), as well as increased concentrations of proinflammatory cytokines (IFN-γ, IL-17) in intestinal homogenate.In mesenteric lymph nodes, however, suppression of the immune response has been observed (decreased ability of cells to proliferate and produce IFN-γ and IL-17 in response to cannavalin A stimulation). Decreased production of IL-10 by mesenteric lymph node cells indicates the formation of a microenvironment that does not allow the activation of a potentially harmful immune response in this tissue. Epicutaneous administration of a higher dose of warfarin leads to an increase in the number of neutrophilic leukocytes and intracellular myeloperoxidase activity, as well as an increase in granular CD11b + cells. In contrast to this increase, a decrease in TNF and IL-6 production as well as mRNA levels for these cytokines was observed.After administration of a higher dose of warfarin, there is a decrease in the number of mononuclear cells with an increase in the presence of CD11b + in this population, but without an effect on cytokine production, indicating the differential effects of transdermal administration of warfarin. Taken together, the results indicate the need to monitor the (adverse) effects of warfarin therapy.
PB  - Belgrade: Immunological Society of Serbia
C3  - VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata
T1  - Immunomodulating effect of oral and transdermal varfarine therapy
T1  - Imunomodulatorni efekti oralne i transdermalne terapije varfarinom
SP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4853
ER  - 

@conference{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Ninkov, Marina and Mileusnić, Dina and Zolotarevski, Lidija and Subota, Vesna and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Warfarin is an anticoagulant that is widely used in the prevention and treatment of thromboembolic disorders in humans. Numerous side effects of oral therapy with this agent are known, which has led to the recommendation for transdermal administration of this agent. This study examined the effect of oral warfarin consumption (0.35 mg / l and 3.5 mg / l in drinking water, 30 days) on the intestinal immune system in rats, as well as the systemic effect (on peripheral blood leukocytes) of epicutaneous administration of this agent. µg or 100 µg, once a day, for three days).The anticoagulant effect, determined on the basis of the increase in prothrombin time, was observed after oral consumption of both doses, as well as after epicutaneous application. Orally administered warfarin leads to histologically evident damage to intestinal tissue and inflammation (cellular infiltration, myeloperoxidase activity, malodialdehyde content and superoxide dismutase and catalase activities), as well as increased concentrations of proinflammatory cytokines (IFN-γ, IL-17) in intestinal homogenate.In mesenteric lymph nodes, however, suppression of the immune response has been observed (decreased ability of cells to proliferate and produce IFN-γ and IL-17 in response to cannavalin A stimulation). Decreased production of IL-10 by mesenteric lymph node cells indicates the formation of a microenvironment that does not allow the activation of a potentially harmful immune response in this tissue. Epicutaneous administration of a higher dose of warfarin leads to an increase in the number of neutrophilic leukocytes and intracellular myeloperoxidase activity, as well as an increase in granular CD11b + cells. In contrast to this increase, a decrease in TNF and IL-6 production as well as mRNA levels for these cytokines was observed.After administration of a higher dose of warfarin, there is a decrease in the number of mononuclear cells with an increase in the presence of CD11b + in this population, but without an effect on cytokine production, indicating the differential effects of transdermal administration of warfarin. Taken together, the results indicate the need to monitor the (adverse) effects of warfarin therapy.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata",
title = "Immunomodulating effect of oral and transdermal varfarine therapy, Imunomodulatorni efekti oralne i transdermalne terapije varfarinom",
pages = "33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4853"
}

Mirkov, I., Popov Aleksandrov, A., Demenesku, J., Ninkov, M., Mileusnić, D., Zolotarevski, L., Subota, V., Kataranovski, D.,& Kataranovski, M.. (2016). Immunomodulating effect of oral and transdermal varfarine therapy. in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata
Belgrade: Immunological Society of Serbia., 33.
https://hdl.handle.net/21.15107/rcub_ibiss_4853

Mirkov I, Popov Aleksandrov A, Demenesku J, Ninkov M, Mileusnić D, Zolotarevski L, Subota V, Kataranovski D, Kataranovski M. Immunomodulating effect of oral and transdermal varfarine therapy. in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata. 2016;:33.
https://hdl.handle.net/21.15107/rcub_ibiss_4853 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Ninkov, Marina, Mileusnić, Dina, Zolotarevski, Lidija, Subota, Vesna, Kataranovski, Dragan, Kataranovski, Milena, "Immunomodulating effect of oral and transdermal varfarine therapy" in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata (2016):33,
https://hdl.handle.net/21.15107/rcub_ibiss_4853 .