TY  - THES
AU  - Ćuruvija, Ivana
PY  - 2022
UR  - https://eteze.bg.ac.rs/application/showtheses?thesesId=9053
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:29011/bdef:Content/download
UR  - https://plus.cobiss.net/cobiss/sr/sr/bib/62302985
UR  - https://nardus.mpn.gov.rs/handle/123456789/21381
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4838
AB  - Starenje se povezuje sa razvojem sistemskog, sterilnog hroničnog zapaljenja (engl.„inflammaging”). Malo je podataka o uticaju genetskih faktora i pola na sposobnost makrofaga(Mφ), kao ključnih ćelija urođenog imunskog odgovora, da tokom starenja “kontrolišu”rezoluciju akutnog zapaljenja i time razvoj hroničnog zapaljenja. Ciljevi ove disertacije su bilida se ispita 1) uticaj rane faze reproduktivnog starenja na fenotipske osobine (ekspresijamarkera povezanih sa aktivacijom i poreklom/funkcijom) i funkcijska svojstva (fagocitoza,sinteza inflamatornih medijatora) Mφ “mirne” i inflamirane (delovanjem tioglikolata)peritonealne duplje ženki Albino Oxford (AO) pacova, 2) značaj genetskih faktora zareproduktivnim starenjem uslovljene promene peritonealnih Mφ od značaja za uspešnurezoluciju akutnog zapaljenja i 3) uloga polnih steroida u nastanku ovih promena uporednomanalizom promena kod mužjaka i ženki AO pacova, njihovom analizom kod ženki AO pacovakojima su na kraju reproduktivnog perioda uklonjeni jajnici i ispitivanjem delovanjaestradiola na Mφ mladih i sredovečnih ženki AO pacova in vitro. Rezultati su pokazali da: 1) sesposobnost Mφ ženki AO pacova da “kontrolišu” rezoluciju akutnog zapaljenja menja većtokom rane faze reproduktivnog starenja, kao i da su ove promene sojno specifične (Mφsredovečnih ženki AO pacova koje “uspešnije” stare od ženki Dark Agouti pacova pokazujusvojstva koja se mogu povezati sa boljom “kontrolom” inflamacije); 2) su ove promene polnospecifične (Mφ sredovečnih ženki imaju svojstva koja ukazuju na veći kapacitet da“kontrolišu” inflamaciju od Mφ mužjaka istog uzrasta) i 3) u nastanku promena relevantnih zasposobnost Mφ ženki AO pacova da “kontrolišu” akutnu inflamaciju važnu ulogu imajupromene u delovanju i estradiola i progesterona. Dodatno, ispitavanja in vitro su ukazala da suza uzrasno zavisne promene u sposobnosti Mφ da “kontrolišu” inflamaciju pored promene ukoncentraciji estradiola važne i one u samim Mφ, koje menjaju njihov odgovor na delovanjeestradiola.
AB  - Aging is associated with the development of systemic, sterile chronic inflammation("inflammaging"). Little is known about the influence of genetic factors and sex on the abilityof macrophages (Mφ), as key innate immune cells, to "control" the resolution of acuteinflammation and thus the development of chronic inflammation during aging. The objectivesof this dissertation were to examine 1) the influence of the early phase of reproductive agingon phenotypic characteristics (expression of markers associated with activation andorigin/function) and functional characteristics (phagocytosis, synthesis of inflammatorymediators) of Mφ isolated from “naive” and inflamed (thioglycollate-induced) peritonealcavity of females Albino Oxford (AO) rats; 2) the significance of genetic factors forreproductive aging-related changes of peritoneal Mφ, especially those important forsuccessful resolution of acute inflammation and 3) the role of sex steroids in the occurrence ofthese changes by comparative analysis in males and females of AO rats, their analysis infemale AO rats whose ovaries were removed at the end of the reproductive period and byexamining in vitro effect of estradiol on Mφ from young and middle-aged female AO rats. Theresults showed that: 1) the ability of Mφ from AO females to “control” the resolution of acuteinflammation changes during the early phase of reproductive aging, and these changes arestrain-specific (Mφ from middle-aged AO females that “age more successful” than Dark Agoutifemales, show properties which may be associated with better "control" of inflammation); 2)these changes are sex-specific (Mφ from middle-aged females have a greater capacity to“control” inflammation than Mφ from males of the same age group) and 3) both estradiol andprogesterone play important roles in the ability of Mφ from AO females to “control” acuteinflammation. In vitro studies revealed that, in addition to changes in estradiol concentration,intrinsic changes in Mφ that regulate their response to estradiol action are important for age-dependent changes in Mφ ability to „control“ inflammation.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju
UR  - https://hdl.handle.net/21.15107/rcub_nardus_21381
ER  - 

@phdthesis{
author = "Ćuruvija, Ivana",
year = "2022",
abstract = "Starenje se povezuje sa razvojem sistemskog, sterilnog hroničnog zapaljenja (engl.„inflammaging”). Malo je podataka o uticaju genetskih faktora i pola na sposobnost makrofaga(Mφ), kao ključnih ćelija urođenog imunskog odgovora, da tokom starenja “kontrolišu”rezoluciju akutnog zapaljenja i time razvoj hroničnog zapaljenja. Ciljevi ove disertacije su bilida se ispita 1) uticaj rane faze reproduktivnog starenja na fenotipske osobine (ekspresijamarkera povezanih sa aktivacijom i poreklom/funkcijom) i funkcijska svojstva (fagocitoza,sinteza inflamatornih medijatora) Mφ “mirne” i inflamirane (delovanjem tioglikolata)peritonealne duplje ženki Albino Oxford (AO) pacova, 2) značaj genetskih faktora zareproduktivnim starenjem uslovljene promene peritonealnih Mφ od značaja za uspešnurezoluciju akutnog zapaljenja i 3) uloga polnih steroida u nastanku ovih promena uporednomanalizom promena kod mužjaka i ženki AO pacova, njihovom analizom kod ženki AO pacovakojima su na kraju reproduktivnog perioda uklonjeni jajnici i ispitivanjem delovanjaestradiola na Mφ mladih i sredovečnih ženki AO pacova in vitro. Rezultati su pokazali da: 1) sesposobnost Mφ ženki AO pacova da “kontrolišu” rezoluciju akutnog zapaljenja menja većtokom rane faze reproduktivnog starenja, kao i da su ove promene sojno specifične (Mφsredovečnih ženki AO pacova koje “uspešnije” stare od ženki Dark Agouti pacova pokazujusvojstva koja se mogu povezati sa boljom “kontrolom” inflamacije); 2) su ove promene polnospecifične (Mφ sredovečnih ženki imaju svojstva koja ukazuju na veći kapacitet da“kontrolišu” inflamaciju od Mφ mužjaka istog uzrasta) i 3) u nastanku promena relevantnih zasposobnost Mφ ženki AO pacova da “kontrolišu” akutnu inflamaciju važnu ulogu imajupromene u delovanju i estradiola i progesterona. Dodatno, ispitavanja in vitro su ukazala da suza uzrasno zavisne promene u sposobnosti Mφ da “kontrolišu” inflamaciju pored promene ukoncentraciji estradiola važne i one u samim Mφ, koje menjaju njihov odgovor na delovanjeestradiola., Aging is associated with the development of systemic, sterile chronic inflammation("inflammaging"). Little is known about the influence of genetic factors and sex on the abilityof macrophages (Mφ), as key innate immune cells, to "control" the resolution of acuteinflammation and thus the development of chronic inflammation during aging. The objectivesof this dissertation were to examine 1) the influence of the early phase of reproductive agingon phenotypic characteristics (expression of markers associated with activation andorigin/function) and functional characteristics (phagocytosis, synthesis of inflammatorymediators) of Mφ isolated from “naive” and inflamed (thioglycollate-induced) peritonealcavity of females Albino Oxford (AO) rats; 2) the significance of genetic factors forreproductive aging-related changes of peritoneal Mφ, especially those important forsuccessful resolution of acute inflammation and 3) the role of sex steroids in the occurrence ofthese changes by comparative analysis in males and females of AO rats, their analysis infemale AO rats whose ovaries were removed at the end of the reproductive period and byexamining in vitro effect of estradiol on Mφ from young and middle-aged female AO rats. Theresults showed that: 1) the ability of Mφ from AO females to “control” the resolution of acuteinflammation changes during the early phase of reproductive aging, and these changes arestrain-specific (Mφ from middle-aged AO females that “age more successful” than Dark Agoutifemales, show properties which may be associated with better "control" of inflammation); 2)these changes are sex-specific (Mφ from middle-aged females have a greater capacity to“control” inflammation than Mφ from males of the same age group) and 3) both estradiol andprogesterone play important roles in the ability of Mφ from AO females to “control” acuteinflammation. In vitro studies revealed that, in addition to changes in estradiol concentration,intrinsic changes in Mφ that regulate their response to estradiol action are important for age-dependent changes in Mφ ability to „control“ inflammation.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju",
url = "https://hdl.handle.net/21.15107/rcub_nardus_21381"
}

Ćuruvija, I.. (2022). Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_21381

Ćuruvija I. Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju. in Универзитет у Београду. 2022;.
https://hdl.handle.net/21.15107/rcub_nardus_21381 .

Ćuruvija, Ivana, "Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju" in Универзитет у Београду (2022),
https://hdl.handle.net/21.15107/rcub_nardus_21381 .

TY  - CONF
AU  - Prijić, Ivana
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5089
AB  - Претпоставља се да дисфункција симпатичког нервног система 
доприноси развоју мултипле склерозе и експерименталног аутоимунског 
енцефаломијелитиса (ЕАЕ). Имајући у виду важност микроглије за 
развој/резолуцију неуроинфламације, испитиван је имуномодулаторни 
потенцијал главног симпатичког медијатора норадреналина коришћењем 
пацовског модела ЕАЕ-а. Резултати су показали да третман пропранололом, 
неселективним блокатором β-адренергичких рецептора, у ефекторској 
фази ЕАЕ-а смањује тежину болести. Ово је корелирало са повећаном 
заступљеношћу микроглије која експримира CX3CR1, кључан молекул за 
њену имуномодулаторну/неуропротективну активност, и њеном појачаном 
експресијом Nrf2 гена, као и гена за хем оксигеназу-1, која се сматра 
ефекторским молекулом анти-инфламаторног CX3CR1/Nrf2 сигналног 
пута. Истраживања in vitro показала су да активација β-адренергичких 
рецептора доводи до нисходне регулације експресије Nrf2 и путем 
независним од CX3CR1. Сходно претходним резултатима, пропранолол 
је повећао фагоцитну способност микроглије, што је корелирало са 
повећањем површинске експресије анти-инфламаторних маркера CD163 
и CD83. Повећање експресије хем оксигеназе-1 праћено је порастом 
заступљености микроглије која синтетише IL-10, а смањењем удела оне 
која експримира проинфламаторне цитокине IL-1β и IL-23. Пропранолол 
је смањио и експресију MCP-1/CCL2 у кичменој мождини. Консекутивно, 
инфилтрација кичмене мождине мијелоидним ћелијама и CD4+ Т-ћелијама 
била је смањена код пацова третираних пропранололом. У складу са свим 
претходним, пропранолол је лимитирао и реактивацију/пролиферацију 
CD4+ Т-лимфоцита и њихову диференцијацију у изузетно патогене IL 17+IFN-γ+GM-CSF+ ћелије. Студија указује да норадреналин, делујући 
посредством β-адренергичких рецептора, подстиче неуроинфламацију 
у ЕАЕ-у тако што модулише експресију Nrf2 у ћелијама микроглије. 
Такође, она представља могућу полазну основу за будућа транслациона 
фармаколошка истраживања у циљу дизајнирања нових приступа у лечењу 
мултипле склерозе.
PB  - Српска академија наука и уметности
PB  - Друштво имунолога Србије
C3  - Научни скуп - Светски дан имунологије 2021, 29. април 2021. године, Београд
T1  - Блокада β-адренергичких рецептора појачава имунорегулаторна/имунопротективна својства микроглије: испитивање на моделу експерименталног аутоимунског енцефаломијелитиса
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5089
ER  - 

@conference{
author = "Prijić, Ivana and Pilipović, Ivan and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2021",
abstract = "Претпоставља се да дисфункција симпатичког нервног система 
доприноси развоју мултипле склерозе и експерименталног аутоимунског 
енцефаломијелитиса (ЕАЕ). Имајући у виду важност микроглије за 
развој/резолуцију неуроинфламације, испитиван је имуномодулаторни 
потенцијал главног симпатичког медијатора норадреналина коришћењем 
пацовског модела ЕАЕ-а. Резултати су показали да третман пропранололом, 
неселективним блокатором β-адренергичких рецептора, у ефекторској 
фази ЕАЕ-а смањује тежину болести. Ово је корелирало са повећаном 
заступљеношћу микроглије која експримира CX3CR1, кључан молекул за 
њену имуномодулаторну/неуропротективну активност, и њеном појачаном 
експресијом Nrf2 гена, као и гена за хем оксигеназу-1, која се сматра 
ефекторским молекулом анти-инфламаторног CX3CR1/Nrf2 сигналног 
пута. Истраживања in vitro показала су да активација β-адренергичких 
рецептора доводи до нисходне регулације експресије Nrf2 и путем 
независним од CX3CR1. Сходно претходним резултатима, пропранолол 
је повећао фагоцитну способност микроглије, што је корелирало са 
повећањем површинске експресије анти-инфламаторних маркера CD163 
и CD83. Повећање експресије хем оксигеназе-1 праћено је порастом 
заступљености микроглије која синтетише IL-10, а смањењем удела оне 
која експримира проинфламаторне цитокине IL-1β и IL-23. Пропранолол 
је смањио и експресију MCP-1/CCL2 у кичменој мождини. Консекутивно, 
инфилтрација кичмене мождине мијелоидним ћелијама и CD4+ Т-ћелијама 
била је смањена код пацова третираних пропранололом. У складу са свим 
претходним, пропранолол је лимитирао и реактивацију/пролиферацију 
CD4+ Т-лимфоцита и њихову диференцијацију у изузетно патогене IL 17+IFN-γ+GM-CSF+ ћелије. Студија указује да норадреналин, делујући 
посредством β-адренергичких рецептора, подстиче неуроинфламацију 
у ЕАЕ-у тако што модулише експресију Nrf2 у ћелијама микроглије. 
Такође, она представља могућу полазну основу за будућа транслациона 
фармаколошка истраживања у циљу дизајнирања нових приступа у лечењу 
мултипле склерозе.",
publisher = "Српска академија наука и уметности, Друштво имунолога Србије",
journal = "Научни скуп - Светски дан имунологије 2021, 29. април 2021. године, Београд",
title = "Блокада β-адренергичких рецептора појачава имунорегулаторна/имунопротективна својства микроглије: испитивање на моделу експерименталног аутоимунског енцефаломијелитиса",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5089"
}

Prijić, I., Pilipović, I., Stojić-Vukanić, Z.,& Leposavić, G.. (2021). Блокада β-адренергичких рецептора појачава имунорегулаторна/имунопротективна својства микроглије: испитивање на моделу експерименталног аутоимунског енцефаломијелитиса. in Научни скуп - Светски дан имунологије 2021, 29. април 2021. године, Београд
Српска академија наука и уметности..
https://hdl.handle.net/21.15107/rcub_farfar_5089

Prijić I, Pilipović I, Stojić-Vukanić Z, Leposavić G. Блокада β-адренергичких рецептора појачава имунорегулаторна/имунопротективна својства микроглије: испитивање на моделу експерименталног аутоимунског енцефаломијелитиса. in Научни скуп - Светски дан имунологије 2021, 29. април 2021. године, Београд. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_5089 .

Prijić, Ivana, Pilipović, Ivan, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Блокада β-адренергичких рецептора појачава имунорегулаторна/имунопротективна својства микроглије: испитивање на моделу експерименталног аутоимунског енцефаломијелитиса" in Научни скуп - Светски дан имунологије 2021, 29. април 2021. године, Београд (2021),
https://hdl.handle.net/21.15107/rcub_farfar_5089 .

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Bufan, Biljana
AU  - Stojanović, Marija
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3529
AB  - The study investigated influence of sex and age on splenic myeloid dendritic cells (DCs) from Dark Agouti rats. Freshly isolated DCs from young males exhibited less mature phenotype and greater endocytic capacity compared with those from age-matched females. Upon LPS stimulation in vitro they were less potent in stimulating allogeneic CD4+ cells in mixed leukocyte reaction (MLR), due to lower expression of MHC II, and greater NO and IL-10 production. In accordance with higher TGF-β production, young male rat DCs were less potent in stimulating IL-17 production in MLR than those from young females. Irrespective of sex, endocytic capacity and responsiveness of DCs to LPS stimulation in culture, judging by their allostimulatory capacity in MLR decreased with age, reflecting decline in MHC II surface density followed by their greater NO production; the effects more prominent in females. Additionally, compared with LPS-stimulated DCs from young rats, those from sex-matched aged rats were more potent in stimulating IL-10 production in MLR, whereas capacity of DCs from aged female and male rats to stimulate IL-17 production remained unaltered and decreased, respectively. This reflected age-related shift in IL-6/TGF-β production level ratio in LPS-stimulated DC cultures towards TGF-β, and sex-specific age-related remodeling CD4+ cell cytokine pathways. Additionally, compared with LPS-stimulated DCs from young rats, those cells from sex-matched aged rats were less potent in stimulating IFN-γ production in MLR, the effect particularly prominent in MLRs encompassing male rat DCs. The study showed that stimulatory and polarizing capacity of DCs depends on rat sex and age.
PB  - Springer Nature
T2  - Biogerontology
T1  - Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells
VL  - 21
IS  - 1
SP  - 83
EP  - 107
DO  - 10.1007/s10522-019-09845-y
ER  - 

@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Bufan, Biljana and Stojanović, Marija and Leposavić, Gordana",
year = "2020",
abstract = "The study investigated influence of sex and age on splenic myeloid dendritic cells (DCs) from Dark Agouti rats. Freshly isolated DCs from young males exhibited less mature phenotype and greater endocytic capacity compared with those from age-matched females. Upon LPS stimulation in vitro they were less potent in stimulating allogeneic CD4+ cells in mixed leukocyte reaction (MLR), due to lower expression of MHC II, and greater NO and IL-10 production. In accordance with higher TGF-β production, young male rat DCs were less potent in stimulating IL-17 production in MLR than those from young females. Irrespective of sex, endocytic capacity and responsiveness of DCs to LPS stimulation in culture, judging by their allostimulatory capacity in MLR decreased with age, reflecting decline in MHC II surface density followed by their greater NO production; the effects more prominent in females. Additionally, compared with LPS-stimulated DCs from young rats, those from sex-matched aged rats were more potent in stimulating IL-10 production in MLR, whereas capacity of DCs from aged female and male rats to stimulate IL-17 production remained unaltered and decreased, respectively. This reflected age-related shift in IL-6/TGF-β production level ratio in LPS-stimulated DC cultures towards TGF-β, and sex-specific age-related remodeling CD4+ cell cytokine pathways. Additionally, compared with LPS-stimulated DCs from young rats, those cells from sex-matched aged rats were less potent in stimulating IFN-γ production in MLR, the effect particularly prominent in MLRs encompassing male rat DCs. The study showed that stimulatory and polarizing capacity of DCs depends on rat sex and age.",
publisher = "Springer Nature",
journal = "Biogerontology",
title = "Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells",
volume = "21",
number = "1",
pages = "83-107",
doi = "10.1007/s10522-019-09845-y"
}

Stojić-Vukanić, Z., Pilipović, I., Bufan, B., Stojanović, M.,& Leposavić, G.. (2020). Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells. in Biogerontology
Springer Nature., 21(1), 83-107.
https://doi.org/10.1007/s10522-019-09845-y

Stojić-Vukanić Z, Pilipović I, Bufan B, Stojanović M, Leposavić G. Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells. in Biogerontology. 2020;21(1):83-107.
doi:10.1007/s10522-019-09845-y .

Stojić-Vukanić, Zorica, Pilipović, Ivan, Bufan, Biljana, Stojanović, Marija, Leposavić, Gordana, "Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells" in Biogerontology, 21, no. 1 (2020):83-107,
https://doi.org/10.1007/s10522-019-09845-y . .

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Prijić, Ivana
AU  - Jasnić, Nebojša
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3509
AB  - Sympathetic dysfunction is suggested to contribute to development of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) alike. Considering important role of microglia in development/resolution of neuroinflammation, contribution of noradrenaline, the key sympathetic end-point mediator, in modulation of microglial phenotypic and functional properties in rat EAE model was examined. The study showed that noradrenaline acting in neurocrine and autocrine/paracrine way might influence microglia during EAE. Propranolol treatment over the effector phase moderated EAE course. This was associated with the increased proportion of microglia expressing CX3CR1, the key molecule in their immunomodulatory/neuroprotective action, and upregulation of CX3CR1 downstream Nrf2 gene. This correlated with the increased heme oxygenase-1 (HO-1) expression and phagocytic capacity of microglia, and their phenotypic changes mirrored in increased proportion of CD163- and CD83-expressing cells. The enhanced HO-1 expression was linked with the decreased proportion of microglial cells expressing IL-1β and IL-23, and possibly IL-6, followed by increased proportion of IL- 10–expressing microglia, and downregulated MCP-1/CCL2 expression. Consistently, spinal cord infiltration with blood-borne myeloid and CD4+ T cells, as well as CD4+ T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17+ cells co-producing IFN-γ and GM-CSF were decreased in propranolol-treated rats compared with saline-injected controls. The in vitro investigations of the effects of noradrenaline on microglia showed that noradrenaline through β-adrenoceptor may influence Nrf2 expression also via CX3CR1-independent route. The study suggests β-adrenoceptor–mediated neuroinflammation-promoting role of noradrenaline in EAE via modulation of microglial Nrf2 expression, and thereby forms the basis for further translational pharmacological research to improve multiple sclerosis therapy.
PB  - Elsevier
T2  - Neurobiology of Disease
T1  - Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia
VL  - 134
DO  - 10.1016/j.nbd.2019.104665
ER  - 

@article{
author = "Pilipović, Ivan and Stojić-Vukanić, Zorica and Prijić, Ivana and Jasnić, Nebojša and Leposavić, Gordana",
year = "2020",
abstract = "Sympathetic dysfunction is suggested to contribute to development of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) alike. Considering important role of microglia in development/resolution of neuroinflammation, contribution of noradrenaline, the key sympathetic end-point mediator, in modulation of microglial phenotypic and functional properties in rat EAE model was examined. The study showed that noradrenaline acting in neurocrine and autocrine/paracrine way might influence microglia during EAE. Propranolol treatment over the effector phase moderated EAE course. This was associated with the increased proportion of microglia expressing CX3CR1, the key molecule in their immunomodulatory/neuroprotective action, and upregulation of CX3CR1 downstream Nrf2 gene. This correlated with the increased heme oxygenase-1 (HO-1) expression and phagocytic capacity of microglia, and their phenotypic changes mirrored in increased proportion of CD163- and CD83-expressing cells. The enhanced HO-1 expression was linked with the decreased proportion of microglial cells expressing IL-1β and IL-23, and possibly IL-6, followed by increased proportion of IL- 10–expressing microglia, and downregulated MCP-1/CCL2 expression. Consistently, spinal cord infiltration with blood-borne myeloid and CD4+ T cells, as well as CD4+ T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17+ cells co-producing IFN-γ and GM-CSF were decreased in propranolol-treated rats compared with saline-injected controls. The in vitro investigations of the effects of noradrenaline on microglia showed that noradrenaline through β-adrenoceptor may influence Nrf2 expression also via CX3CR1-independent route. The study suggests β-adrenoceptor–mediated neuroinflammation-promoting role of noradrenaline in EAE via modulation of microglial Nrf2 expression, and thereby forms the basis for further translational pharmacological research to improve multiple sclerosis therapy.",
publisher = "Elsevier",
journal = "Neurobiology of Disease",
title = "Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia",
volume = "134",
doi = "10.1016/j.nbd.2019.104665"
}

Pilipović, I., Stojić-Vukanić, Z., Prijić, I., Jasnić, N.,& Leposavić, G.. (2020). Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia. in Neurobiology of Disease
Elsevier., 134.
https://doi.org/10.1016/j.nbd.2019.104665

Pilipović I, Stojić-Vukanić Z, Prijić I, Jasnić N, Leposavić G. Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia. in Neurobiology of Disease. 2020;134.
doi:10.1016/j.nbd.2019.104665 .

Pilipović, Ivan, Stojić-Vukanić, Zorica, Prijić, Ivana, Jasnić, Nebojša, Leposavić, Gordana, "Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia" in Neurobiology of Disease, 134 (2020),
https://doi.org/10.1016/j.nbd.2019.104665 . .

TY  - JOUR
AU  - Pilipović, Iivan
AU  - Stojić-Vukanić, Zorica
AU  - Prijić, Ivana
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3503
AB  - The role of stress effector systems in the initiation and progression of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, has strongly been suggested. To corroborate this notion, alterations in activity of the sympathoadrenal and sympathoneural axes of sympathoadrenal system (a major communication pathway between the central nervous system and the immune system), mirrored in altered release of their end-point mediators (adrenaline and noradrenaline, respectively), are shown to precede (in MS) and/or occur during development of MS and EAE in response to immune cell activation (in early phase of disease) and disease-related damage of sympathoadrenal system neurons and their projections (in late phase of disease). To add to the complexity, innate immunity cells and T-lymphocytes synthesize noradrenaline that may be implicated in a local autocrine/paracrine self-amplifying feed-forward loop to enhance myeloid-cell synthesis of proinflammatory cytokines and inflammatory injury. Furthermore, experimental manipulations targeting noradrenaline/adrenaline action are shown to influence clinical outcome of EAE, in a disease phase-specific manner. This is partly related to the fact that virtually all types of cells involved in the instigation and progression of autoimmune inflammation and target tissue damage in EAE/MS express functional adrenoceptors. Although catecholamines exert majority of immunomodulatory effects through β2-adrenoceptor, a role for α-adrenoceptors in EAE pathogenesis has also been indicated. In this review, we summarize all aforementioned aspects of immunopathogenetic action of catecholamines in EAE/MS as possibly important for designing new strategies targeting their action to prevent/mitigate autoimmune neuroinflammation and tissue damage.
PB  - Frontiers Media S.A.
T2  - Frontiers in Endocrinology
T1  - Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
VL  - 10
DO  - 10.3389/fendo.2019.00921
ER  - 

@article{
author = "Pilipović, Iivan and Stojić-Vukanić, Zorica and Prijić, Ivana and Leposavić, Gordana",
year = "2020",
abstract = "The role of stress effector systems in the initiation and progression of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, has strongly been suggested. To corroborate this notion, alterations in activity of the sympathoadrenal and sympathoneural axes of sympathoadrenal system (a major communication pathway between the central nervous system and the immune system), mirrored in altered release of their end-point mediators (adrenaline and noradrenaline, respectively), are shown to precede (in MS) and/or occur during development of MS and EAE in response to immune cell activation (in early phase of disease) and disease-related damage of sympathoadrenal system neurons and their projections (in late phase of disease). To add to the complexity, innate immunity cells and T-lymphocytes synthesize noradrenaline that may be implicated in a local autocrine/paracrine self-amplifying feed-forward loop to enhance myeloid-cell synthesis of proinflammatory cytokines and inflammatory injury. Furthermore, experimental manipulations targeting noradrenaline/adrenaline action are shown to influence clinical outcome of EAE, in a disease phase-specific manner. This is partly related to the fact that virtually all types of cells involved in the instigation and progression of autoimmune inflammation and target tissue damage in EAE/MS express functional adrenoceptors. Although catecholamines exert majority of immunomodulatory effects through β2-adrenoceptor, a role for α-adrenoceptors in EAE pathogenesis has also been indicated. In this review, we summarize all aforementioned aspects of immunopathogenetic action of catecholamines in EAE/MS as possibly important for designing new strategies targeting their action to prevent/mitigate autoimmune neuroinflammation and tissue damage.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Endocrinology",
title = "Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis",
volume = "10",
doi = "10.3389/fendo.2019.00921"
}

Pilipović, I., Stojić-Vukanić, Z., Prijić, I.,& Leposavić, G.. (2020). Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. in Frontiers in Endocrinology
Frontiers Media S.A.., 10.
https://doi.org/10.3389/fendo.2019.00921

Pilipović I, Stojić-Vukanić Z, Prijić I, Leposavić G. Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. in Frontiers in Endocrinology. 2020;10.
doi:10.3389/fendo.2019.00921 .

Pilipović, Iivan, Stojić-Vukanić, Zorica, Prijić, Ivana, Leposavić, Gordana, "Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis" in Frontiers in Endocrinology, 10 (2020),
https://doi.org/10.3389/fendo.2019.00921 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3504
AB  - The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-γ/IL-4 production ratio was shifted towards IFN-γ. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research.
PB  - Springer Nature
T2  - Scientific Reports
T1  - Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis
VL  - 10
IS  - 1
DO  - 10.1038/s41598-020-58127-y
ER  - 

@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana",
year = "2020",
abstract = "The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-γ/IL-4 production ratio was shifted towards IFN-γ. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research.",
publisher = "Springer Nature",
journal = "Scientific Reports",
title = "Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis",
volume = "10",
number = "1",
doi = "10.1038/s41598-020-58127-y"
}

Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2020). Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis. in Scientific Reports
Springer Nature., 10(1).
https://doi.org/10.1038/s41598-020-58127-y

Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis. in Scientific Reports. 2020;10(1).
doi:10.1038/s41598-020-58127-y .

Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis" in Scientific Reports, 10, no. 1 (2020),
https://doi.org/10.1038/s41598-020-58127-y . .

TY  - JOUR
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3521
AB  - Considering variability in vaccine responsiveness across human populations, in respect to magnitude and quality, and importance of vaccines in the elderly, the influence of recipient genetic background on the kinetics of age-related changes in the serum IgG antibody responses to seasonal trivalent inactivated split-virus influenza bulk (TIV) was studied in BALB/c and C57BL/6 mice showing quantitative and qualitative differences in this responses in young adult ages. With ageing the total serum IgG response to influenza viruses declined, in a strain-specific manner, so the strain disparity observed in young adult mice (the greater magnitude of IgG response in BALB/c mice) disappeared in aged mice. However, the sexual dimorphisms in this response (more prominent in females of both strains) remained in aged ones. The strain-specific differences in age-related decline in the magnitude of IgG response to TIV correlated with the number of germinal centre (GC) B splenocytes. The age-related decline in GC B cell number was consistent with the decrease in the proliferation of B cells and CD4+ cells in splenocyte cultures upon restimulation with TIV. Additionally, the age-related decrease in the magnitude of IgG response correlated with the increase in follicular T regulatory (fTreg)/follicular T helper (fTh) and fTreg/GC B splenocyte ratios (reflecting decrease in fTh and GC B numbers without changes in fTreg number), and the frequency of CD4+ splenocytes producing IL-21, a key factor in balancing the B cell and fTreg cell activity. With ageing the avidity of virus influenza-specific antibody increased in females of both strains. Moreover, ageing affected IgG2a/IgG1 and IgG2c/IgG1 ratios (reflecting Th1/Th2 balance) in male BALB/c mice and female C57BL/6 mice, respectively. Consequently, differently from young mice exhibiting the similar ratios in male and female mice, in aged female mice of both strains IgG2a(c)/IgG1 ratios were shifted towards a less effective IgG1 response (stimulated by IL-4 cytokines) compared with males. The age-related alterations in IgG subclass profiles in both strains correlated with those in IFN-γ/IL-4 production level ratio in splenocyte cultures restimulated with TIV. These findings stimulate further research to formulate sex-specific strategies to improve efficacy of influenza vaccine in the elderly.
PB  - Elsevier
T2  - Experimental Gerontology
T1  - Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences
VL  - 133
DO  - 10.1016/j.exger.2020.110857
ER  - 

@article{
author = "Bufan, Biljana and Arsenović-Ranin, Nevena and Petrović, Raisa and Živković, Irena and Stoiljković, Vera and Leposavić, Gordana",
year = "2020",
abstract = "Considering variability in vaccine responsiveness across human populations, in respect to magnitude and quality, and importance of vaccines in the elderly, the influence of recipient genetic background on the kinetics of age-related changes in the serum IgG antibody responses to seasonal trivalent inactivated split-virus influenza bulk (TIV) was studied in BALB/c and C57BL/6 mice showing quantitative and qualitative differences in this responses in young adult ages. With ageing the total serum IgG response to influenza viruses declined, in a strain-specific manner, so the strain disparity observed in young adult mice (the greater magnitude of IgG response in BALB/c mice) disappeared in aged mice. However, the sexual dimorphisms in this response (more prominent in females of both strains) remained in aged ones. The strain-specific differences in age-related decline in the magnitude of IgG response to TIV correlated with the number of germinal centre (GC) B splenocytes. The age-related decline in GC B cell number was consistent with the decrease in the proliferation of B cells and CD4+ cells in splenocyte cultures upon restimulation with TIV. Additionally, the age-related decrease in the magnitude of IgG response correlated with the increase in follicular T regulatory (fTreg)/follicular T helper (fTh) and fTreg/GC B splenocyte ratios (reflecting decrease in fTh and GC B numbers without changes in fTreg number), and the frequency of CD4+ splenocytes producing IL-21, a key factor in balancing the B cell and fTreg cell activity. With ageing the avidity of virus influenza-specific antibody increased in females of both strains. Moreover, ageing affected IgG2a/IgG1 and IgG2c/IgG1 ratios (reflecting Th1/Th2 balance) in male BALB/c mice and female C57BL/6 mice, respectively. Consequently, differently from young mice exhibiting the similar ratios in male and female mice, in aged female mice of both strains IgG2a(c)/IgG1 ratios were shifted towards a less effective IgG1 response (stimulated by IL-4 cytokines) compared with males. The age-related alterations in IgG subclass profiles in both strains correlated with those in IFN-γ/IL-4 production level ratio in splenocyte cultures restimulated with TIV. These findings stimulate further research to formulate sex-specific strategies to improve efficacy of influenza vaccine in the elderly.",
publisher = "Elsevier",
journal = "Experimental Gerontology",
title = "Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences",
volume = "133",
doi = "10.1016/j.exger.2020.110857"
}

Bufan, B., Arsenović-Ranin, N., Petrović, R., Živković, I., Stoiljković, V.,& Leposavić, G.. (2020). Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences. in Experimental Gerontology
Elsevier., 133.
https://doi.org/10.1016/j.exger.2020.110857

Bufan B, Arsenović-Ranin N, Petrović R, Živković I, Stoiljković V, Leposavić G. Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences. in Experimental Gerontology. 2020;133.
doi:10.1016/j.exger.2020.110857 .

Bufan, Biljana, Arsenović-Ranin, Nevena, Petrović, Raisa, Živković, Irena, Stoiljković, Vera, Leposavić, Gordana, "Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences" in Experimental Gerontology, 133 (2020),
https://doi.org/10.1016/j.exger.2020.110857 . .

TY  - THES
AU  - Đuretić, Jasmina
PY  - 2019
UR  - http://nardus.mpn.gov.rs/handle/123456789/12127
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7258
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:21006/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=2048398178
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3687
AB  - Starenje utiče na incidenciju većine inflamatornih autoimunskih bolesti, što se povezuje sa starenjem imunskog sistema, tzv. imunološkim starenjem (engl. immunosenescence). Budući da je pokazano da postoje značajne individualne razlike u procesu starenja ispitivan je značaj genetskih faktora (sojnih razlika) za starenjem uslovljene promene u incidenciji inflamatornih autoimunskih bolesti kod pacova. Korišćen je model eksperimentalnog autoimunskog encefalomijelitisa (EAE) indukovanog inokulacijom homogenata singene kičmene moždine u kompletnom Frojndovom adjuvansu uz ko-administraciju inaktivisane Bordetella pertussis, koji mimikrira ranu inflamatornu fazu multiple skleroze, najčešće inflamatorne autoimunske bolesti centralnog nervnog sistema, čija incidencija pokazuje jasnu uzrasnu zavisnost (smanjuje se starenjem). U istraživanja su uključene adultne i stare ženke pacova Dark Agouti (DA) soja, koji pokazuju izrazitu osetljivost na indukciju EAE-a u adultnom uzrastu i pacova Albino Oxford (AO) soja, koji su u adultnom uzrastu relativno rezistentni na indukciju EAE-a. Cilj je bio i da se definišu ćelijski i molekularni mehanizmi, koji bi mogli da budu odgovorni za moguće sojno zavisne starenjem uzrokovane razlike u osetljivosti na indukciju ove bolesti.Rezultati dobijeni u okviru ove doktorske disertacije pokazali su da starenje smanjuje incidenciju EAE-a i težinu bolesti kod DA pacova, a da kod AO pacova dovodi do razvoja bolesti blagog protrahovanog toka, koja pokazuje značajnu incidenciju (62,5%). Razlike u kliničkom ispoljavanju bolesti kod ova dva soja pacova su se mogle povezati sa sojnim razlikama u mehanizmima koji su uključeni u kontrolu intenziteta primarnog (auto)imunskog odgovora u drenirajućim limfnim čvorovima, ali i migracije aktivisanih neuroantigen-specifičnih T pomoćničkih 17 (engl. T helper 17, Th17) ćelija, posebno zadržavanja u slezini (ekspresija CD44s molekula na površini Th ćelija i zastupljenost CD4+CD25+Foxp3+ regulatornih T-limfocita), kao ključnih za razvoj bolesti u ovom modelu, u ciljni organ (kičmenu moždinu) i autoimunskogodgovora i inflamacije u kičmenoj moždini...
AB  - Aging affects the incidence of most inflammatory autoimmune diseases, which is associated with the aging of the immune system, the so-called immunosenescence. Since it has been shown that there are significant individual differences in the aging process, the significance of genetic factors (strain differences) for age-related changes in the incidence of inflammatory autoimmune diseases in rats was investigated. The model of experimental autoimmune encephalomyelitis (EAE) induced by inoculation of the syngenic spinal cord homogenate in a complete Freund's adjuvant with co-administration of inactivated Bordetella pertussis was used. This model mimics the early inflammatory phase of multiple sclerosis, the most common inflammatory autoimmune disease of the central nervous system, whose incidence shows a clear age dependency (decreases with aging). Young adult and aged female rats of Dark Agouti (DA) strain, which show high susceptibility to EAE induction at an young adult age and rats of Albino Oxford (AO) strain, which are relatively resistant to EAE induction at an young adult age were used in this research. The aim of this doctoral dissertation was to define cellular and molecular mechanisms that could be responsible for presumed strain specificities in age-related changes in the disease induction and development.The results obtained in this doctoral dissertation showed that aging decreases the incidence of EAE and the disease severity in DA rats, while in AO rats it leads to development of mild clinical disease of prolonged duration, exhibiting a significant incidence (62.5%). Differences in the clinical manifestations of the disease in these two rat strains could be associated with strain differences in the mechanisms involved in controlling the intensity of the primary (auto) immune response in the draining lymph nodes, but also the migration of activated neuroantigen-specific T helper 17 (Th17) cells, in particular their retention in the spleen (Th cell surface expression of CD44s molecule and the frequency of CD4+CD25+Foxp3+ regulatory T lymphocytes), the key cells for the development of the disease in this model, to the target organ (spinal cord)and autoimmune response and inflammation in the spinal cord..
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Uticaj starenja na imunski odgovor i neuroinflamaciju: ispitivanja na modelu eksperimentalnog autoimunskog encefalomijelitisa
UR  - https://hdl.handle.net/21.15107/rcub_nardus_12127
ER  - 

@phdthesis{
author = "Đuretić, Jasmina",
year = "2019",
abstract = "Starenje utiče na incidenciju većine inflamatornih autoimunskih bolesti, što se povezuje sa starenjem imunskog sistema, tzv. imunološkim starenjem (engl. immunosenescence). Budući da je pokazano da postoje značajne individualne razlike u procesu starenja ispitivan je značaj genetskih faktora (sojnih razlika) za starenjem uslovljene promene u incidenciji inflamatornih autoimunskih bolesti kod pacova. Korišćen je model eksperimentalnog autoimunskog encefalomijelitisa (EAE) indukovanog inokulacijom homogenata singene kičmene moždine u kompletnom Frojndovom adjuvansu uz ko-administraciju inaktivisane Bordetella pertussis, koji mimikrira ranu inflamatornu fazu multiple skleroze, najčešće inflamatorne autoimunske bolesti centralnog nervnog sistema, čija incidencija pokazuje jasnu uzrasnu zavisnost (smanjuje se starenjem). U istraživanja su uključene adultne i stare ženke pacova Dark Agouti (DA) soja, koji pokazuju izrazitu osetljivost na indukciju EAE-a u adultnom uzrastu i pacova Albino Oxford (AO) soja, koji su u adultnom uzrastu relativno rezistentni na indukciju EAE-a. Cilj je bio i da se definišu ćelijski i molekularni mehanizmi, koji bi mogli da budu odgovorni za moguće sojno zavisne starenjem uzrokovane razlike u osetljivosti na indukciju ove bolesti.Rezultati dobijeni u okviru ove doktorske disertacije pokazali su da starenje smanjuje incidenciju EAE-a i težinu bolesti kod DA pacova, a da kod AO pacova dovodi do razvoja bolesti blagog protrahovanog toka, koja pokazuje značajnu incidenciju (62,5%). Razlike u kliničkom ispoljavanju bolesti kod ova dva soja pacova su se mogle povezati sa sojnim razlikama u mehanizmima koji su uključeni u kontrolu intenziteta primarnog (auto)imunskog odgovora u drenirajućim limfnim čvorovima, ali i migracije aktivisanih neuroantigen-specifičnih T pomoćničkih 17 (engl. T helper 17, Th17) ćelija, posebno zadržavanja u slezini (ekspresija CD44s molekula na površini Th ćelija i zastupljenost CD4+CD25+Foxp3+ regulatornih T-limfocita), kao ključnih za razvoj bolesti u ovom modelu, u ciljni organ (kičmenu moždinu) i autoimunskogodgovora i inflamacije u kičmenoj moždini..., Aging affects the incidence of most inflammatory autoimmune diseases, which is associated with the aging of the immune system, the so-called immunosenescence. Since it has been shown that there are significant individual differences in the aging process, the significance of genetic factors (strain differences) for age-related changes in the incidence of inflammatory autoimmune diseases in rats was investigated. The model of experimental autoimmune encephalomyelitis (EAE) induced by inoculation of the syngenic spinal cord homogenate in a complete Freund's adjuvant with co-administration of inactivated Bordetella pertussis was used. This model mimics the early inflammatory phase of multiple sclerosis, the most common inflammatory autoimmune disease of the central nervous system, whose incidence shows a clear age dependency (decreases with aging). Young adult and aged female rats of Dark Agouti (DA) strain, which show high susceptibility to EAE induction at an young adult age and rats of Albino Oxford (AO) strain, which are relatively resistant to EAE induction at an young adult age were used in this research. The aim of this doctoral dissertation was to define cellular and molecular mechanisms that could be responsible for presumed strain specificities in age-related changes in the disease induction and development.The results obtained in this doctoral dissertation showed that aging decreases the incidence of EAE and the disease severity in DA rats, while in AO rats it leads to development of mild clinical disease of prolonged duration, exhibiting a significant incidence (62.5%). Differences in the clinical manifestations of the disease in these two rat strains could be associated with strain differences in the mechanisms involved in controlling the intensity of the primary (auto) immune response in the draining lymph nodes, but also the migration of activated neuroantigen-specific T helper 17 (Th17) cells, in particular their retention in the spleen (Th cell surface expression of CD44s molecule and the frequency of CD4+CD25+Foxp3+ regulatory T lymphocytes), the key cells for the development of the disease in this model, to the target organ (spinal cord)and autoimmune response and inflammation in the spinal cord..",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Uticaj starenja na imunski odgovor i neuroinflamaciju: ispitivanja na modelu eksperimentalnog autoimunskog encefalomijelitisa",
url = "https://hdl.handle.net/21.15107/rcub_nardus_12127"
}

Đuretić, J.. (2019). Uticaj starenja na imunski odgovor i neuroinflamaciju: ispitivanja na modelu eksperimentalnog autoimunskog encefalomijelitisa. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_12127

Đuretić J. Uticaj starenja na imunski odgovor i neuroinflamaciju: ispitivanja na modelu eksperimentalnog autoimunskog encefalomijelitisa. in Универзитет у Београду. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_12127 .

Đuretić, Jasmina, "Uticaj starenja na imunski odgovor i neuroinflamaciju: ispitivanja na modelu eksperimentalnog autoimunskog encefalomijelitisa" in Универзитет у Београду (2019),
https://hdl.handle.net/21.15107/rcub_nardus_12127 .

TY  - JOUR
AU  - Đuretić, Jasmina
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3571
AB  - Natural killer (NK) cells, influencing dendritic cell (DC)-mediated CD4+ lymphocyte priming in draining lymph nodes (dLNs) and controlling spinal cord (SC) infiltration with encephalitogenic CD4+T lymphocytes, modulate EAE (multiple sclerosis model). This study examined their putative contribution to age-related differences in EAE development in Dark Agouti (DA) (exhibiting age-related decrease in EAE susceptibility) and Albino Oxford (AO) (becoming susceptible to EAE with aging) rats. Aging increased NK cell number in dLNs from rats of both strains. In AO rats, but not in DA ones, it also increased the numbers of IFN-γ-producing NK cells (important for DC activation) and activated/matured DCs, thereby increasing activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated CD25+Foxp3-CD4+ cell number. Aging in DA rats diminished activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated Foxp3-CD4+ cell number. However, MBP-stimulated CD4+ cell proliferation did not differ in dLN cell cultures from young and aged AO rats (as more favorable activated/matured DC/Foxp3-CD4+ cell ratio was abrogated by lower intrinsic CD4+ cell proliferative capacity and a greater regulatory CD25+Foxp3+CD4+ lymphocyte frequency), but was lower in those from aged compared with young DA rats. At SC level, aging shifted Foxp3-CD4+/cytotoxic CX3CR1+ NK cell ratio towards the former in AO rats, so it was less favorable in aged AO rats exhibiting prolonged neurological deficit compared with their DA counterparts. The study showed strain and age differences in number of IFN-γ-producing NK cells in EAE rat dLNs, and suggested that their pathogenetic relevance depends on frequency and/or activity of other cells involved in CD4+ T cell (auto)immune response.
PB  - Termedia Publishing House Ltd.
T2  - Central European Journal of Immunology
T1  - Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): Lessons from research on rats with distinct age and strain
VL  - 44
IS  - 4
SP  - 337
EP  - 356
DO  - 10.5114/ceji.2019.92777
ER  - 

@article{
author = "Đuretić, Jasmina and Pilipović, Ivan and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2019",
abstract = "Natural killer (NK) cells, influencing dendritic cell (DC)-mediated CD4+ lymphocyte priming in draining lymph nodes (dLNs) and controlling spinal cord (SC) infiltration with encephalitogenic CD4+T lymphocytes, modulate EAE (multiple sclerosis model). This study examined their putative contribution to age-related differences in EAE development in Dark Agouti (DA) (exhibiting age-related decrease in EAE susceptibility) and Albino Oxford (AO) (becoming susceptible to EAE with aging) rats. Aging increased NK cell number in dLNs from rats of both strains. In AO rats, but not in DA ones, it also increased the numbers of IFN-γ-producing NK cells (important for DC activation) and activated/matured DCs, thereby increasing activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated CD25+Foxp3-CD4+ cell number. Aging in DA rats diminished activated/matured DC/conventional Foxp3-CD4+ cell ratio and activated Foxp3-CD4+ cell number. However, MBP-stimulated CD4+ cell proliferation did not differ in dLN cell cultures from young and aged AO rats (as more favorable activated/matured DC/Foxp3-CD4+ cell ratio was abrogated by lower intrinsic CD4+ cell proliferative capacity and a greater regulatory CD25+Foxp3+CD4+ lymphocyte frequency), but was lower in those from aged compared with young DA rats. At SC level, aging shifted Foxp3-CD4+/cytotoxic CX3CR1+ NK cell ratio towards the former in AO rats, so it was less favorable in aged AO rats exhibiting prolonged neurological deficit compared with their DA counterparts. The study showed strain and age differences in number of IFN-γ-producing NK cells in EAE rat dLNs, and suggested that their pathogenetic relevance depends on frequency and/or activity of other cells involved in CD4+ T cell (auto)immune response.",
publisher = "Termedia Publishing House Ltd.",
journal = "Central European Journal of Immunology",
title = "Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): Lessons from research on rats with distinct age and strain",
volume = "44",
number = "4",
pages = "337-356",
doi = "10.5114/ceji.2019.92777"
}

Đuretić, J., Pilipović, I., Stojić-Vukanić, Z.,& Leposavić, G.. (2019). Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): Lessons from research on rats with distinct age and strain. in Central European Journal of Immunology
Termedia Publishing House Ltd.., 44(4), 337-356.
https://doi.org/10.5114/ceji.2019.92777

Đuretić J, Pilipović I, Stojić-Vukanić Z, Leposavić G. Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): Lessons from research on rats with distinct age and strain. in Central European Journal of Immunology. 2019;44(4):337-356.
doi:10.5114/ceji.2019.92777 .

Đuretić, Jasmina, Pilipović, Ivan, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Natural killer cells as participants in pathogenesis of rat experimental autoimmune encephalomyelitis (EAE): Lessons from research on rats with distinct age and strain" in Central European Journal of Immunology, 44, no. 4 (2019):337-356,
https://doi.org/10.5114/ceji.2019.92777 . .

TY  - CONF
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5087
AB  - Collagen-induced arthritis (CIA) is a well-established experimental model mimicking 
many immunopathogenic and clinical aspects of rheumatoid arthritis (RA), including 
sexual dimorphism in the clinical presentation. Our previous study showed that a more 
severe disease in female compared with male rats correlated with more robust Th17 
response reflecting sexual dimorphism in Th17/Treg axis plasticity. Given that 
autoantibodies play a significant role in the immunopathogenesis of RA and CIA, in 
the present study the germinal center (GC) reaction in the lymph nodes draining 
inflamed joints and adjacent tissue (dLNs) was examined for putative sexual 
dimorphism. Female rats mounted greater serum collagen II-specific IgG response than 
their male counterparts. This dimorphism correlated with the higher frequency of GC 
B cells in female compared with male dLNs. Consistently, the frequency of 
activated/proliferating Ki67+ cells among dLN B cells was higher in females than in 
males. This was associated with the shift in dLN T follicular regulatory (Tfr)/T 
follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of 
CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell 
frequency in females was consistent with the greater dLN expression of mRNA for IL 21/27, the key cytokines involved in Tfh cell generation and help to B cells. 
Additionally, in collagen II-stimulated female rat dLN cell cultures, IFN-γ/IL-4 ratio 
was shifted towards IFN-γ. Consistently, serum ratio between pathogenic IgG2a and 
protective IgG1 collagen II-specific antibodies was shifted towards the former in 
females. Thus, the study suggests that targeting T/B cell interactions should be 
considered in further translation research aimed to design sex-specific therapies for RA.
PB  - Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia
PB  - Immunological Society of Serbia
C3  - Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book
T1  - Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5087
ER  - 

@conference{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana",
year = "2019",
abstract = "Collagen-induced arthritis (CIA) is a well-established experimental model mimicking 
many immunopathogenic and clinical aspects of rheumatoid arthritis (RA), including 
sexual dimorphism in the clinical presentation. Our previous study showed that a more 
severe disease in female compared with male rats correlated with more robust Th17 
response reflecting sexual dimorphism in Th17/Treg axis plasticity. Given that 
autoantibodies play a significant role in the immunopathogenesis of RA and CIA, in 
the present study the germinal center (GC) reaction in the lymph nodes draining 
inflamed joints and adjacent tissue (dLNs) was examined for putative sexual 
dimorphism. Female rats mounted greater serum collagen II-specific IgG response than 
their male counterparts. This dimorphism correlated with the higher frequency of GC 
B cells in female compared with male dLNs. Consistently, the frequency of 
activated/proliferating Ki67+ cells among dLN B cells was higher in females than in 
males. This was associated with the shift in dLN T follicular regulatory (Tfr)/T 
follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of 
CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell 
frequency in females was consistent with the greater dLN expression of mRNA for IL 21/27, the key cytokines involved in Tfh cell generation and help to B cells. 
Additionally, in collagen II-stimulated female rat dLN cell cultures, IFN-γ/IL-4 ratio 
was shifted towards IFN-γ. Consistently, serum ratio between pathogenic IgG2a and 
protective IgG1 collagen II-specific antibodies was shifted towards the former in 
females. Thus, the study suggests that targeting T/B cell interactions should be 
considered in further translation research aimed to design sex-specific therapies for RA.",
publisher = "Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia, Immunological Society of Serbia",
journal = "Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book",
title = "Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5087"
}

Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2019). Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells. in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book
Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia..
https://hdl.handle.net/21.15107/rcub_farfar_5087

Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells. in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book. 2019;.
https://hdl.handle.net/21.15107/rcub_farfar_5087 .

Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells" in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book (2019),
https://hdl.handle.net/21.15107/rcub_farfar_5087 .

TY  - CONF
AU  - Pilipović, Ivan
AU  - Prijić, Ivana
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5085
AB  - Sympathetic dysfunction was proposed to participate in development of multiple sclerosis and 
its animal model, experimental autoimmune encephalomyelitis (EAE). This may be linked with 
findings indicating that noradrenaline, the key sympathetic end-point mediator, through β adrenoceptor exerts immunomodulatory action. Considering importance of the target tissue for 
the clinical outcome of EAE, the study investigated the effects of propranolol, a non-selective β adrenoceptor blocker, on the disease severity in Dark Agouti rats. Administration of propranolol 
over the effector phase of EAE substantially moderated neurological symptoms of the disease. 
This correlated with the increased proportion of spinal cord microglia expressing CX3CR1, the 
crucial neuroinflammation-limiting molecule, and upregulated expression of Nrf2, the key 
CX3CR1 downstream target gene. Additionally, in spinal cord of propranolol-administered rats 
the expression of heme-oxigenase 1, Nrf2 target gene, was upregulated. Consequently, microglia 
from propranolol-administered rats, exhibited increased proportion of IL-10–expressing cells, 
but decreased those of IL-1β– and IL-23–expressing ones. Propranolol also downregulated the 
IL-6 and MCP-1/CCL2 expression in spinal cord. Furthermore, propranolol affecting 
CXCR1/Nrf2 signaling pathway enhanced microglial phagocytic/endocytic capacity and surface 
expression of anti-inflammatory CD163/CD83 markers. Results from in vitro pharmacological 
study examining influence of noradrenaline/propranolol on functional properties of microglia 
showed that microglia synthesize noradrenaline, which, in turn, through β-adrenoceptor, 
downregulated their Nrf2 expression, in a CX3CR1-independent manner. In accordance with 
microglial shift towards a more anti-inflammatory profile, in spinal cord of propranolol administered rats was found: i) decreased infiltration with blood-borne myeloid and CD4+ T 
cells, and ii) reduced CD4+ T-cell reactivation/proliferation and differentiation into highly 
pathogenic IL-17+ cells co-producing IFN-γ and GM-CSF. The study suggests a 
neuroinflammation-promoting role for central noradrenaline in EAE, via β-adrenoceptor–
mediated modulation of microglial Nrf2 expression. Thus, it points out to a putative target for 
future translational pharmacological research to optimize multiple sclerosis therapy. Funding: 
MPNTR RS (grant number 175050)
PB  - Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia
PB  - Immunological Society of Serbia
C3  - Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8.  2019, Abstract book
T1  - Propranolol reduced severity of EAE by increasing the expression Nrf2 in microglia
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5085
ER  - 

@conference{
author = "Pilipović, Ivan and Prijić, Ivana and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2019",
abstract = "Sympathetic dysfunction was proposed to participate in development of multiple sclerosis and 
its animal model, experimental autoimmune encephalomyelitis (EAE). This may be linked with 
findings indicating that noradrenaline, the key sympathetic end-point mediator, through β adrenoceptor exerts immunomodulatory action. Considering importance of the target tissue for 
the clinical outcome of EAE, the study investigated the effects of propranolol, a non-selective β adrenoceptor blocker, on the disease severity in Dark Agouti rats. Administration of propranolol 
over the effector phase of EAE substantially moderated neurological symptoms of the disease. 
This correlated with the increased proportion of spinal cord microglia expressing CX3CR1, the 
crucial neuroinflammation-limiting molecule, and upregulated expression of Nrf2, the key 
CX3CR1 downstream target gene. Additionally, in spinal cord of propranolol-administered rats 
the expression of heme-oxigenase 1, Nrf2 target gene, was upregulated. Consequently, microglia 
from propranolol-administered rats, exhibited increased proportion of IL-10–expressing cells, 
but decreased those of IL-1β– and IL-23–expressing ones. Propranolol also downregulated the 
IL-6 and MCP-1/CCL2 expression in spinal cord. Furthermore, propranolol affecting 
CXCR1/Nrf2 signaling pathway enhanced microglial phagocytic/endocytic capacity and surface 
expression of anti-inflammatory CD163/CD83 markers. Results from in vitro pharmacological 
study examining influence of noradrenaline/propranolol on functional properties of microglia 
showed that microglia synthesize noradrenaline, which, in turn, through β-adrenoceptor, 
downregulated their Nrf2 expression, in a CX3CR1-independent manner. In accordance with 
microglial shift towards a more anti-inflammatory profile, in spinal cord of propranolol administered rats was found: i) decreased infiltration with blood-borne myeloid and CD4+ T 
cells, and ii) reduced CD4+ T-cell reactivation/proliferation and differentiation into highly 
pathogenic IL-17+ cells co-producing IFN-γ and GM-CSF. The study suggests a 
neuroinflammation-promoting role for central noradrenaline in EAE, via β-adrenoceptor–
mediated modulation of microglial Nrf2 expression. Thus, it points out to a putative target for 
future translational pharmacological research to optimize multiple sclerosis therapy. Funding: 
MPNTR RS (grant number 175050)",
publisher = "Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia, Immunological Society of Serbia",
journal = "Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8.  2019, Abstract book",
title = "Propranolol reduced severity of EAE by increasing the expression Nrf2 in microglia",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5085"
}

Pilipović, I., Prijić, I., Stojić-Vukanić, Z.,& Leposavić, G.. (2019). Propranolol reduced severity of EAE by increasing the expression Nrf2 in microglia. in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8.  2019, Abstract book
Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia..
https://hdl.handle.net/21.15107/rcub_farfar_5085

Pilipović I, Prijić I, Stojić-Vukanić Z, Leposavić G. Propranolol reduced severity of EAE by increasing the expression Nrf2 in microglia. in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8.  2019, Abstract book. 2019;.
https://hdl.handle.net/21.15107/rcub_farfar_5085 .

Pilipović, Ivan, Prijić, Ivana, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Propranolol reduced severity of EAE by increasing the expression Nrf2 in microglia" in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8.  2019, Abstract book (2019),
https://hdl.handle.net/21.15107/rcub_farfar_5085 .

TY  - JOUR
AU  - Vujnović, Ivana
AU  - Pilipović, Ivan
AU  - Jasnić, Nebojša
AU  - Petrović, Raisa
AU  - Blagojević, Veljko
AU  - Arsenović-Ranin, Nevena
AU  - Stojić-Vukanić, Zorica
AU  - Đorđević, Jelena
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3323
AB  - Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4 + T-cell (auto) immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (beta-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4 + T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of beta(2)-adrenoceptor-expressing CD4 + T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4 + lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1 beta and IL-23/p19 expression and IL-17 + CD4 + cell frequency, but enhanced IL-17 production only in male rat CD4 + lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, beta-adrenoceptor-mediated signalling may contribute to sex bias in rat IL-17-producing cell secretory capacity.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Cellular Immunology
T1  - Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?
VL  - 336
SP  - 48
EP  - 57
DO  - 10.1016/j.cellimm.2018.12.009
ER  - 

@article{
author = "Vujnović, Ivana and Pilipović, Ivan and Jasnić, Nebojša and Petrović, Raisa and Blagojević, Veljko and Arsenović-Ranin, Nevena and Stojić-Vukanić, Zorica and Đorđević, Jelena and Leposavić, Gordana",
year = "2019",
abstract = "Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4 + T-cell (auto) immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (beta-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4 + T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of beta(2)-adrenoceptor-expressing CD4 + T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4 + lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1 beta and IL-23/p19 expression and IL-17 + CD4 + cell frequency, but enhanced IL-17 production only in male rat CD4 + lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, beta-adrenoceptor-mediated signalling may contribute to sex bias in rat IL-17-producing cell secretory capacity.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Cellular Immunology",
title = "Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?",
volume = "336",
pages = "48-57",
doi = "10.1016/j.cellimm.2018.12.009"
}

Vujnović, I., Pilipović, I., Jasnić, N., Petrović, R., Blagojević, V., Arsenović-Ranin, N., Stojić-Vukanić, Z., Đorđević, J.,& Leposavić, G.. (2019). Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?. in Cellular Immunology
Academic Press Inc Elsevier Science, San Diego., 336, 48-57.
https://doi.org/10.1016/j.cellimm.2018.12.009

Vujnović I, Pilipović I, Jasnić N, Petrović R, Blagojević V, Arsenović-Ranin N, Stojić-Vukanić Z, Đorđević J, Leposavić G. Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?. in Cellular Immunology. 2019;336:48-57.
doi:10.1016/j.cellimm.2018.12.009 .

Vujnović, Ivana, Pilipović, Ivan, Jasnić, Nebojša, Petrović, Raisa, Blagojević, Veljko, Arsenović-Ranin, Nevena, Stojić-Vukanić, Zorica, Đorđević, Jelena, Leposavić, Gordana, "Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?" in Cellular Immunology, 336 (2019):48-57,
https://doi.org/10.1016/j.cellimm.2018.12.009 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3295
AB  - Collagen type II-induced arthritis (CIA) in Dark Agouti rats, a model of rheumatoid arthritis (RA), reproduces sexual dimorphism in the incidence and severity of the human disease. Th17 cells are central in the induction/propagation of autoimmune inflammation in CIA and RA. To assess mechanisms underlying this dimorphism in CIA rats, in lymph nodes draining inflamed joints and adjacent tissues (dLNs) from CIA rats of both sexes Th17/CD25 + Foxp3 + CD4 + T-regulatory cell (Treg) ratio, Th17 cell redifferentiation in functionally distinct subsets and Treg transdifferentiation into IL-17-producing cells (exTregs) were examined. In female rats (developing more severe CIA than their male counterparts) the higher frequency of all Th17 cells (reflecting partly their greater proliferation), followed by the higher frequency of highly pathogenic IFN-gamma/GM-CSF-co-producing cells, but lower frequency of less pathogenic/immunoregulatory IL-10-producing cells among them was found. Additionally, compared with male rats, in female rats the lower frequency of Tregs was observed. Moreover, Tregs from female rats exhibited diminished proliferative and suppressive capacity (judging by PD-1 expression) and enhanced conversion into IL-17-producing cells. Given that TGF-beta concentration was comparable in collagen-type II-stimulated dLN cell cultures from female and male rats, the shift in Th17/Treg ratio followed by augmented Th17 cell redifferentiation into IFN-gamma/GM-CSF-co-producing cells and Treg transdifferentiation into IL-17-producing cells in female rats was associated with increased concentration of IL-6 in female rat dLN cell cultures, and the higher frequency of IL-1 beta- and IL-23-producing cells among their dLN cells. The lower frequency of IL-10-producing B cells, presumably B regulatory cells (Bregs) could also contribute to the shift in Th17/Treg ratio in female rat compared with male rat dLNs. Consistently, the lower expression of IL-35 (the cytokine promoting Treg expansion directly and indirectly, by favoring Breg expansion and conversion into IL-10/IL-35-producing cells) in female rat dLN cells was detected. Thus, the study identified putative cellular and molecular substrates of the sexual dimorphism in the immunopathogenesis and clinical outcome of CIA and suggested mechanisms to be targeted in females to improve control of Th17 response, and consequently clinical outcome of CIA, and possibly RA.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Brain Behavior and Immunity
T1  - Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis
VL  - 76
SP  - 198
EP  - 214
DO  - 10.1016/j.bbi.2018.11.311
ER  - 

@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana",
year = "2019",
abstract = "Collagen type II-induced arthritis (CIA) in Dark Agouti rats, a model of rheumatoid arthritis (RA), reproduces sexual dimorphism in the incidence and severity of the human disease. Th17 cells are central in the induction/propagation of autoimmune inflammation in CIA and RA. To assess mechanisms underlying this dimorphism in CIA rats, in lymph nodes draining inflamed joints and adjacent tissues (dLNs) from CIA rats of both sexes Th17/CD25 + Foxp3 + CD4 + T-regulatory cell (Treg) ratio, Th17 cell redifferentiation in functionally distinct subsets and Treg transdifferentiation into IL-17-producing cells (exTregs) were examined. In female rats (developing more severe CIA than their male counterparts) the higher frequency of all Th17 cells (reflecting partly their greater proliferation), followed by the higher frequency of highly pathogenic IFN-gamma/GM-CSF-co-producing cells, but lower frequency of less pathogenic/immunoregulatory IL-10-producing cells among them was found. Additionally, compared with male rats, in female rats the lower frequency of Tregs was observed. Moreover, Tregs from female rats exhibited diminished proliferative and suppressive capacity (judging by PD-1 expression) and enhanced conversion into IL-17-producing cells. Given that TGF-beta concentration was comparable in collagen-type II-stimulated dLN cell cultures from female and male rats, the shift in Th17/Treg ratio followed by augmented Th17 cell redifferentiation into IFN-gamma/GM-CSF-co-producing cells and Treg transdifferentiation into IL-17-producing cells in female rats was associated with increased concentration of IL-6 in female rat dLN cell cultures, and the higher frequency of IL-1 beta- and IL-23-producing cells among their dLN cells. The lower frequency of IL-10-producing B cells, presumably B regulatory cells (Bregs) could also contribute to the shift in Th17/Treg ratio in female rat compared with male rat dLNs. Consistently, the lower expression of IL-35 (the cytokine promoting Treg expansion directly and indirectly, by favoring Breg expansion and conversion into IL-10/IL-35-producing cells) in female rat dLN cells was detected. Thus, the study identified putative cellular and molecular substrates of the sexual dimorphism in the immunopathogenesis and clinical outcome of CIA and suggested mechanisms to be targeted in females to improve control of Th17 response, and consequently clinical outcome of CIA, and possibly RA.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Brain Behavior and Immunity",
title = "Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis",
volume = "76",
pages = "198-214",
doi = "10.1016/j.bbi.2018.11.311"
}

Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2019). Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis. in Brain Behavior and Immunity
Academic Press Inc Elsevier Science, San Diego., 76, 198-214.
https://doi.org/10.1016/j.bbi.2018.11.311

Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis. in Brain Behavior and Immunity. 2019;76:198-214.
doi:10.1016/j.bbi.2018.11.311 .

Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sexual dimorphism in Th17/Treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis" in Brain Behavior and Immunity, 76 (2019):198-214,
https://doi.org/10.1016/j.bbi.2018.11.311 . .

TY  - JOUR
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Kotur-Stevuljević, Jelena
AU  - Petrović, Raisa
AU  - Sopta, Jelena
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3256
AB  - The study investigated mechanisms underlying sex differences in thymic involution in Dark Agouti rats. Adverse effects of aging on thymus were more pronounced in males than in females. Thymi from old males exhibited more prominent: (i) fibro-adipose degeneration which correlated with greater intensity of thymic oxidative stress and enhanced thymic TGF- and IL-6 expression and (ii) decline in thymopoiesis, as suggested by the number of the most mature CD4+CD8-/CD4-CD8+ single positive (SP) TCRhigh thymocytes. The greater accumulation of adipose tissue in old male thymus was linked with greater age-related increase in thymic expression of PPAR and STAT3, a transcription factor regulating the expression of PPAR downstream genes, in male than in female rats. In aged thymi of both sexes the early CD4-CD8- double negative (DN) stage of thymocyte development was affected, so relative accumulation of the least mature CD45RC+CD2- cells followed by decreased frequency of their DN and CD4+CD8+ double positive (DP) TCR- descendants was observed. Additionally, in old males, because of the increased thymic expression of Nur77, a nuclear receptor involved in negative selection, and decreased CD90 (a negative regulator of thymocyte selection threshold) MFI on DP TCRint thymocytes, less efficient positive/more efficient negative selection was found. Moreover, in male rats, thymocyte post-selection differentiation/maturation was skewed towards CD4-CD8+ SP TCRhigh cells compared with age-matched females, reflecting, at least partly, greater IL-15 expression in their thymi. The study indicated mechanisms underlying sex-based differences in age-related thymic changes and consequently necessity of sex-specific approaches in designing strategies to rejuvenate thymus.
PB  - Springer, New York
T2  - Biogerontology
T1  - Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation
VL  - 20
IS  - 4
SP  - 545
EP  - 569
DO  - 10.1007/s10522-019-09816-3
ER  - 

@article{
author = "Nacka-Aleksić, Mirjana and Pilipović, Ivan and Kotur-Stevuljević, Jelena and Petrović, Raisa and Sopta, Jelena and Leposavić, Gordana",
year = "2019",
abstract = "The study investigated mechanisms underlying sex differences in thymic involution in Dark Agouti rats. Adverse effects of aging on thymus were more pronounced in males than in females. Thymi from old males exhibited more prominent: (i) fibro-adipose degeneration which correlated with greater intensity of thymic oxidative stress and enhanced thymic TGF- and IL-6 expression and (ii) decline in thymopoiesis, as suggested by the number of the most mature CD4+CD8-/CD4-CD8+ single positive (SP) TCRhigh thymocytes. The greater accumulation of adipose tissue in old male thymus was linked with greater age-related increase in thymic expression of PPAR and STAT3, a transcription factor regulating the expression of PPAR downstream genes, in male than in female rats. In aged thymi of both sexes the early CD4-CD8- double negative (DN) stage of thymocyte development was affected, so relative accumulation of the least mature CD45RC+CD2- cells followed by decreased frequency of their DN and CD4+CD8+ double positive (DP) TCR- descendants was observed. Additionally, in old males, because of the increased thymic expression of Nur77, a nuclear receptor involved in negative selection, and decreased CD90 (a negative regulator of thymocyte selection threshold) MFI on DP TCRint thymocytes, less efficient positive/more efficient negative selection was found. Moreover, in male rats, thymocyte post-selection differentiation/maturation was skewed towards CD4-CD8+ SP TCRhigh cells compared with age-matched females, reflecting, at least partly, greater IL-15 expression in their thymi. The study indicated mechanisms underlying sex-based differences in age-related thymic changes and consequently necessity of sex-specific approaches in designing strategies to rejuvenate thymus.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation",
volume = "20",
number = "4",
pages = "545-569",
doi = "10.1007/s10522-019-09816-3"
}

Nacka-Aleksić, M., Pilipović, I., Kotur-Stevuljević, J., Petrović, R., Sopta, J.,& Leposavić, G.. (2019). Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation. in Biogerontology
Springer, New York., 20(4), 545-569.
https://doi.org/10.1007/s10522-019-09816-3

Nacka-Aleksić M, Pilipović I, Kotur-Stevuljević J, Petrović R, Sopta J, Leposavić G. Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation. in Biogerontology. 2019;20(4):545-569.
doi:10.1007/s10522-019-09816-3 .

Nacka-Aleksić, Mirjana, Pilipović, Ivan, Kotur-Stevuljević, Jelena, Petrović, Raisa, Sopta, Jelena, Leposavić, Gordana, "Sexual dimorphism in rat thymic involution: a correlation with thymic oxidative status and inflammation" in Biogerontology, 20, no. 4 (2019):545-569,
https://doi.org/10.1007/s10522-019-09816-3 . .

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3556
AB  - Vaccines are considered to be one of the greatest public health achievements of the last century. As a result of widespread vaccine use, the smallpox virus has been completely eradicated and the incidence of other diseases such as polio, measles, tetanus and diphtheria has been drastically reduced. Current licensed vaccines, predominantly composed of either live attenuated or killed pathogens, pathogen subunits, owe their success to their ability to elicit neutralizing antibodies against pathogens. On the other side, cell-mediated immunity, which plays a central role in elimination of intracellular pathogens (which in most cases leads to chronic infections) is much more difficult to obtain using current vaccines. Currently, numerous vector and nucleic acid (DNA and mRNA)-based prophylactic vaccines, capable of inducing substantial vaccine-specific T cell responses, are investigated in preclinical and clinical studies, with promising results. This review focuses the background of vector and nucleic acid-based vaccines, their strengths and weaknesses and safety issues.
AB  - Vakcine se smatraju jednim od najvećih javnozdravstvenih dostignuća prošlog veka. Zahvaljujući vakcinaciji u svetu su potpuno iskorenjene velike boginje, a incidencija drugih infektivnih bolesti, kao što su dečija paraliza, male boginje, tetanus i difterija, drastično je smanjena. Današnje licencirane vakcine, koje pretežno sadrže žive atenuisane ili mrtve patogene ili njihove delove, su uspešne zahvaljujući tome što stimulišu produkciju neutrališućih antitela. Sa druge strane, ove vakcine mnogo teže indukuju ćelijski-posredovanu imunost, koja je važna za eliminaciju intraćelijskih patogena (koji često dovode do hroničnih infekcija). Trenutno se u pretkliničkim i kliničkim studijama ispituju brojne profilaktičke vakcine zasnovane na vektorima i nukleinskim kiselinama (DNK i iRNK), sposobne da indukuju snažan odgovor T-ćelija na vakcinalni antigen, sa obećavajućim rezultatima. U ovom radu su date osnovne informacije o vakcinama sa vektorima i nukleinskim kiselinama, opisani su mehanizmi kojima one pokreću imunski odgovor, njihove dobre i loše strane, kao i problemi vezani za njihovu bezbednu primenu.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - New vaccines on the horizon
T1  - Perspektive u razvoju profilaktičkih vakcina
VL  - 69
IS  - 6
SP  - 385
EP  - 405
DO  - 10.5937/arhfarm1906385A
ER  - 

@article{
author = "Arsenović-Ranin, Nevena",
year = "2019",
abstract = "Vaccines are considered to be one of the greatest public health achievements of the last century. As a result of widespread vaccine use, the smallpox virus has been completely eradicated and the incidence of other diseases such as polio, measles, tetanus and diphtheria has been drastically reduced. Current licensed vaccines, predominantly composed of either live attenuated or killed pathogens, pathogen subunits, owe their success to their ability to elicit neutralizing antibodies against pathogens. On the other side, cell-mediated immunity, which plays a central role in elimination of intracellular pathogens (which in most cases leads to chronic infections) is much more difficult to obtain using current vaccines. Currently, numerous vector and nucleic acid (DNA and mRNA)-based prophylactic vaccines, capable of inducing substantial vaccine-specific T cell responses, are investigated in preclinical and clinical studies, with promising results. This review focuses the background of vector and nucleic acid-based vaccines, their strengths and weaknesses and safety issues., Vakcine se smatraju jednim od najvećih javnozdravstvenih dostignuća prošlog veka. Zahvaljujući vakcinaciji u svetu su potpuno iskorenjene velike boginje, a incidencija drugih infektivnih bolesti, kao što su dečija paraliza, male boginje, tetanus i difterija, drastično je smanjena. Današnje licencirane vakcine, koje pretežno sadrže žive atenuisane ili mrtve patogene ili njihove delove, su uspešne zahvaljujući tome što stimulišu produkciju neutrališućih antitela. Sa druge strane, ove vakcine mnogo teže indukuju ćelijski-posredovanu imunost, koja je važna za eliminaciju intraćelijskih patogena (koji često dovode do hroničnih infekcija). Trenutno se u pretkliničkim i kliničkim studijama ispituju brojne profilaktičke vakcine zasnovane na vektorima i nukleinskim kiselinama (DNK i iRNK), sposobne da indukuju snažan odgovor T-ćelija na vakcinalni antigen, sa obećavajućim rezultatima. U ovom radu su date osnovne informacije o vakcinama sa vektorima i nukleinskim kiselinama, opisani su mehanizmi kojima one pokreću imunski odgovor, njihove dobre i loše strane, kao i problemi vezani za njihovu bezbednu primenu.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "New vaccines on the horizon, Perspektive u razvoju profilaktičkih vakcina",
volume = "69",
number = "6",
pages = "385-405",
doi = "10.5937/arhfarm1906385A"
}

Arsenović-Ranin, N.. (2019). New vaccines on the horizon. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 69(6), 385-405.
https://doi.org/10.5937/arhfarm1906385A

Arsenović-Ranin N. New vaccines on the horizon. in Arhiv za farmaciju. 2019;69(6):385-405.
doi:10.5937/arhfarm1906385A .

Arsenović-Ranin, Nevena, "New vaccines on the horizon" in Arhiv za farmaciju, 69, no. 6 (2019):385-405,
https://doi.org/10.5937/arhfarm1906385A . .

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Bufan, Biljana
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3266
AB  - The study examined sex-specificities in age-related changes in BALB/c mice IgG antibody responses to immunisation with trivalent inactivated split-virus influenza bulk. Aging diminished the total serum IgG antibody responses to H1N1 and H3N2 and B influenza virus antigens in mice of both sexes, but they remained greater in aged females. This sex difference in aged mice correlated with the greater post-immunisation increase in the frequency of spleen germinal centre (GC) B cells and more favourable T follicular regulatory (Tfr)/GC B cell ratio, as Tfr cells are suggested to control antibody production through suppression of glycolysis. The greater post-immunisation GC B cell response in aged females compared with males correlated with the greater proliferation of B cells and CD4+ cells in splenocyte cultures from aged females restimulated with inactivated split-virus influenza from the bulk. To support the greater post-immunisation increase in the frequency GC B cell in aged females was more favourable Tfr/T follicular helper (Tfh) cell ratio. Additionally, compared with aged males, in age-matched females the greater avidity of serum IgG antibodies was found. However, in aged females IgG2a/IgG1 antibody ratio, reflecting spleen Th1/Th2 cytokine balance, was shifted towards IgG1 when compared with age-matched male mice. This shift was ascribed to a more prominent decline in the titres of functionally important IgG2a antibodies in females with aging. The study suggest that biological sex should be considered as a variable in designing strategies to manipulate with immune outcome of immunisation in aged animals, and possibly, at very long distance, humans.
PB  - Springer, New York
T2  - Biogerontology
T1  - Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences
VL  - 20
IS  - 4
SP  - 475
EP  - 496
DO  - 10.1007/s10522-019-09811-8
ER  - 

@article{
author = "Arsenović-Ranin, Nevena and Petrović, Raisa and Živković, Irena and Bufan, Biljana and Stoiljković, Vera and Leposavić, Gordana",
year = "2019",
abstract = "The study examined sex-specificities in age-related changes in BALB/c mice IgG antibody responses to immunisation with trivalent inactivated split-virus influenza bulk. Aging diminished the total serum IgG antibody responses to H1N1 and H3N2 and B influenza virus antigens in mice of both sexes, but they remained greater in aged females. This sex difference in aged mice correlated with the greater post-immunisation increase in the frequency of spleen germinal centre (GC) B cells and more favourable T follicular regulatory (Tfr)/GC B cell ratio, as Tfr cells are suggested to control antibody production through suppression of glycolysis. The greater post-immunisation GC B cell response in aged females compared with males correlated with the greater proliferation of B cells and CD4+ cells in splenocyte cultures from aged females restimulated with inactivated split-virus influenza from the bulk. To support the greater post-immunisation increase in the frequency GC B cell in aged females was more favourable Tfr/T follicular helper (Tfh) cell ratio. Additionally, compared with aged males, in age-matched females the greater avidity of serum IgG antibodies was found. However, in aged females IgG2a/IgG1 antibody ratio, reflecting spleen Th1/Th2 cytokine balance, was shifted towards IgG1 when compared with age-matched male mice. This shift was ascribed to a more prominent decline in the titres of functionally important IgG2a antibodies in females with aging. The study suggest that biological sex should be considered as a variable in designing strategies to manipulate with immune outcome of immunisation in aged animals, and possibly, at very long distance, humans.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences",
volume = "20",
number = "4",
pages = "475-496",
doi = "10.1007/s10522-019-09811-8"
}

Arsenović-Ranin, N., Petrović, R., Živković, I., Bufan, B., Stoiljković, V.,& Leposavić, G.. (2019). Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences. in Biogerontology
Springer, New York., 20(4), 475-496.
https://doi.org/10.1007/s10522-019-09811-8

Arsenović-Ranin N, Petrović R, Živković I, Bufan B, Stoiljković V, Leposavić G. Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences. in Biogerontology. 2019;20(4):475-496.
doi:10.1007/s10522-019-09811-8 .

Arsenović-Ranin, Nevena, Petrović, Raisa, Živković, Irena, Bufan, Biljana, Stoiljković, Vera, Leposavić, Gordana, "Influence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences" in Biogerontology, 20, no. 4 (2019):475-496,
https://doi.org/10.1007/s10522-019-09811-8 . .

TY  - JOUR
AU  - Bufan, Biljana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3562
AB  - Extended lifespan and increasing number of the elderly (>65 years) worldwide carries the challenges for the public health system, as this is the population particularly susceptible to infectious diseases. One way to prevent these diseases is vaccination. In order to improve the quality of life of the elderly, to reduce complications, hospitalizations and mortality, many European countries and the United States recommend the vaccination of the elderly with the influenza vaccine, vaccines against Streptococcus pneumoniae and Varicella-zoster virus (VZV), and booster vaccination against tetanus, pertussis and diphtheria. The reason for the greater susceptibility to infectious diseases, and lower efficacy of vaccines in the elderly, are age-associated changes of the immune system. In most European countries seasonal influenza vaccine is recommended for the individuals over 65 years of age. Its efficacy is lower in the elderly than in adults, so strategies are being developed to overcome these problems (including adjuvants in the formulation, increasing the antigen dose, changing the route of immunization, development of vector-based vaccines). Polysaccharide and conjugated vaccines are available against S. pneumoniae, but data regarding their efficacy are inconsistent. The VZV vaccine is an attenuated, live vaccine and has been shown to be effective in reducing the incidence of herpes zoster and post-herpetic neuralgia. Raising awareness of the importance of vaccination in the elderly and the development of vaccines tailored for this population is of great importance for the preservation of their health. © 2019, Pharmaceutical Association of Serbia.
AB  - Produženje  ljudskog  veka  i  povećanje  broja  starih  (stariji  od  65  godina)  na  svetskom nivou  nosi  sa  sobom  izazove  za  javno-zdravstveni  sistem  jer  se radi  o  populaciji  podložnoj infektivnim  bolestima.  Vakcinacija  je  jedan  od  načina  prevencije  ovih  bolesti.  U  cilju poboljšanja kvaliteta života, smanjenja komplikacija bolesti, hospitalizacija i mortaliteta starih, mnoge  evropske  države  i  Sjedinjene  Američke  Države,  kod  starih osoba,  preporučuju vakcinaciju protiv gripa, pneumokoka, varičela-zoster virusa (VZV), kao i „booster” vakcinacije protiv tetanusa, pertusisa  i difterije. Razlog veće podložnosti infektivnim bolestima i manjoj efikasnosti vakcina kod starih su starenjem uslovljene promene koje pogađaju imunski sistem, a koje utiču na njegovu funkciju. Sezonska vakcina protiv gripa se u većini evropskih zemalja preporučuje starijima od 65 godina. Budući da je njena efikasnost niža kod starih nego kod odraslih osoba, razvijaju se strategije koje bi prevazišle ovaj problem (uključivanje adjuvansa u formulaciju,  povećanje  doze,  promena  puta  unošenja  antigena,  razvoj  vektorskih  vakcina). Protiv  pneumokoka  su  dostupne  polisaharidna  i  konjugovana  vakcina,  a  podaci  o  njihovoj efikasnosti su nekonzistentni. Vakcina protiv VZVje atenuisana, živa vakcina i pokazala se efikasna u smanjenju incidencije herpes zostera i post-herpetične neuralgije.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Application of prophylactic vaccines in the elderly
T1  - Primena profilaktičkih vakcina kod starih
VL  - 69
IS  - 6
SP  - 469
EP  - 489
DO  - 10.5937/arhfarm1906469B
ER  - 

@article{
author = "Bufan, Biljana",
year = "2019",
abstract = "Extended lifespan and increasing number of the elderly (>65 years) worldwide carries the challenges for the public health system, as this is the population particularly susceptible to infectious diseases. One way to prevent these diseases is vaccination. In order to improve the quality of life of the elderly, to reduce complications, hospitalizations and mortality, many European countries and the United States recommend the vaccination of the elderly with the influenza vaccine, vaccines against Streptococcus pneumoniae and Varicella-zoster virus (VZV), and booster vaccination against tetanus, pertussis and diphtheria. The reason for the greater susceptibility to infectious diseases, and lower efficacy of vaccines in the elderly, are age-associated changes of the immune system. In most European countries seasonal influenza vaccine is recommended for the individuals over 65 years of age. Its efficacy is lower in the elderly than in adults, so strategies are being developed to overcome these problems (including adjuvants in the formulation, increasing the antigen dose, changing the route of immunization, development of vector-based vaccines). Polysaccharide and conjugated vaccines are available against S. pneumoniae, but data regarding their efficacy are inconsistent. The VZV vaccine is an attenuated, live vaccine and has been shown to be effective in reducing the incidence of herpes zoster and post-herpetic neuralgia. Raising awareness of the importance of vaccination in the elderly and the development of vaccines tailored for this population is of great importance for the preservation of their health. © 2019, Pharmaceutical Association of Serbia., Produženje  ljudskog  veka  i  povećanje  broja  starih  (stariji  od  65  godina)  na  svetskom nivou  nosi  sa  sobom  izazove  za  javno-zdravstveni  sistem  jer  se radi  o  populaciji  podložnoj infektivnim  bolestima.  Vakcinacija  je  jedan  od  načina  prevencije  ovih  bolesti.  U  cilju poboljšanja kvaliteta života, smanjenja komplikacija bolesti, hospitalizacija i mortaliteta starih, mnoge  evropske  države  i  Sjedinjene  Američke  Države,  kod  starih osoba,  preporučuju vakcinaciju protiv gripa, pneumokoka, varičela-zoster virusa (VZV), kao i „booster” vakcinacije protiv tetanusa, pertusisa  i difterije. Razlog veće podložnosti infektivnim bolestima i manjoj efikasnosti vakcina kod starih su starenjem uslovljene promene koje pogađaju imunski sistem, a koje utiču na njegovu funkciju. Sezonska vakcina protiv gripa se u većini evropskih zemalja preporučuje starijima od 65 godina. Budući da je njena efikasnost niža kod starih nego kod odraslih osoba, razvijaju se strategije koje bi prevazišle ovaj problem (uključivanje adjuvansa u formulaciju,  povećanje  doze,  promena  puta  unošenja  antigena,  razvoj  vektorskih  vakcina). Protiv  pneumokoka  su  dostupne  polisaharidna  i  konjugovana  vakcina,  a  podaci  o  njihovoj efikasnosti su nekonzistentni. Vakcina protiv VZVje atenuisana, živa vakcina i pokazala se efikasna u smanjenju incidencije herpes zostera i post-herpetične neuralgije.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Application of prophylactic vaccines in the elderly, Primena profilaktičkih vakcina kod starih",
volume = "69",
number = "6",
pages = "469-489",
doi = "10.5937/arhfarm1906469B"
}

Bufan, B.. (2019). Application of prophylactic vaccines in the elderly. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 69(6), 469-489.
https://doi.org/10.5937/arhfarm1906469B

Bufan B. Application of prophylactic vaccines in the elderly. in Arhiv za farmaciju. 2019;69(6):469-489.
doi:10.5937/arhfarm1906469B .

Bufan, Biljana, "Application of prophylactic vaccines in the elderly" in Arhiv za farmaciju, 69, no. 6 (2019):469-489,
https://doi.org/10.5937/arhfarm1906469B . .

TY  - JOUR
AU  - Nacka-Aleksić, Mirjana
AU  - Stojanović, Marija
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3221
AB  - An accumulating body of evidence suggests that development of autoimmune pathologies leads to thymic dysfunction and changes in peripheral T-cell compartment, which, in turn, perpetuate their pathogenesis. To test this hypothesis, thymocyte differentiation/maturation in rats susceptible (Dark Agouti, DA) and relatively resistant (Albino Oxford, AO) to experimental autoimmune encephalomyelitis (EAE) induction was examined. Irrespective of strain, immunization for EAE (i) increased the circulating levels of IL-6, a cytokine causally linked with thymic atrophy, and (ii) led to thymic atrophy reflecting partly enhanced thymocyte apoptosis associated with downregulated thymic IL-7 expression. Additionally, immunization diminished the expression of Thy-1, a negative regulator of TCR alpha beta-mediated signaling and activation thresholds, on CD4+CD8+ TCR alpha beta(lo/hi) thymocytes undergoing selection and thereby impaired thymocyte selection/survival. This diminished the generation of mature CD4+ and CD8+ single positive TCR alpha beta(hi) thymocytes and, consequently, CD4+ and CD8+ recent thymic emigrants. In immunized rats, thymic differentiation of natural regulatory CD4+Foxp3+CD25+ T cells (nTregs) was particularly affected reflecting a diminished expression of IL-7, IL-2 and IL-15. The decline in the overall thymic T-cell output and nTreg generation was more pronounced in DA than AO rats. Additionally, differently from immunized AO rats, in DA ones the frequency of CD28- cells secreting cytolytic enzymes within peripheral blood CD4+ T lymphocytes increased, as a consequence of thymic atrophy-related replicative stress (mirrored in CD4+ cell memory pool expansion and p16(INK4a) accumulation). The higher circulating level of TNF-alpha in DA compared with AO rats could also contribute to this difference. Consistently, higher frequency of cytolytic CD4+ granzyme B+ cells (associated with greater tissue damage) was found in spinal cord of immunized DA rats compared with their AO counterparts. In conclusion, the study indicated that strain differences in immunization-induced changes in thymopoiesis and peripheral CD4+CD28- T-cell generation could contribute to rat strain-specific clinical outcomes of immunization for EAE.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization
VL  - 13
IS  - 8
DO  - 10.1371/journal.pone.0201848
ER  - 

@article{
author = "Nacka-Aleksić, Mirjana and Stojanović, Marija and Pilipović, Ivan and Stojić-Vukanić, Zorica and Kosec, Duško and Leposavić, Gordana",
year = "2018",
abstract = "An accumulating body of evidence suggests that development of autoimmune pathologies leads to thymic dysfunction and changes in peripheral T-cell compartment, which, in turn, perpetuate their pathogenesis. To test this hypothesis, thymocyte differentiation/maturation in rats susceptible (Dark Agouti, DA) and relatively resistant (Albino Oxford, AO) to experimental autoimmune encephalomyelitis (EAE) induction was examined. Irrespective of strain, immunization for EAE (i) increased the circulating levels of IL-6, a cytokine causally linked with thymic atrophy, and (ii) led to thymic atrophy reflecting partly enhanced thymocyte apoptosis associated with downregulated thymic IL-7 expression. Additionally, immunization diminished the expression of Thy-1, a negative regulator of TCR alpha beta-mediated signaling and activation thresholds, on CD4+CD8+ TCR alpha beta(lo/hi) thymocytes undergoing selection and thereby impaired thymocyte selection/survival. This diminished the generation of mature CD4+ and CD8+ single positive TCR alpha beta(hi) thymocytes and, consequently, CD4+ and CD8+ recent thymic emigrants. In immunized rats, thymic differentiation of natural regulatory CD4+Foxp3+CD25+ T cells (nTregs) was particularly affected reflecting a diminished expression of IL-7, IL-2 and IL-15. The decline in the overall thymic T-cell output and nTreg generation was more pronounced in DA than AO rats. Additionally, differently from immunized AO rats, in DA ones the frequency of CD28- cells secreting cytolytic enzymes within peripheral blood CD4+ T lymphocytes increased, as a consequence of thymic atrophy-related replicative stress (mirrored in CD4+ cell memory pool expansion and p16(INK4a) accumulation). The higher circulating level of TNF-alpha in DA compared with AO rats could also contribute to this difference. Consistently, higher frequency of cytolytic CD4+ granzyme B+ cells (associated with greater tissue damage) was found in spinal cord of immunized DA rats compared with their AO counterparts. In conclusion, the study indicated that strain differences in immunization-induced changes in thymopoiesis and peripheral CD4+CD28- T-cell generation could contribute to rat strain-specific clinical outcomes of immunization for EAE.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization",
volume = "13",
number = "8",
doi = "10.1371/journal.pone.0201848"
}

Nacka-Aleksić, M., Stojanović, M., Pilipović, I., Stojić-Vukanić, Z., Kosec, D.,& Leposavić, G.. (2018). Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization. in PLoS One
Public Library Science, San Francisco., 13(8).
https://doi.org/10.1371/journal.pone.0201848

Nacka-Aleksić M, Stojanović M, Pilipović I, Stojić-Vukanić Z, Kosec D, Leposavić G. Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization. in PLoS One. 2018;13(8).
doi:10.1371/journal.pone.0201848 .

Nacka-Aleksić, Mirjana, Stojanović, Marija, Pilipović, Ivan, Stojić-Vukanić, Zorica, Kosec, Duško, Leposavić, Gordana, "Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization" in PLoS One, 13, no. 8 (2018),
https://doi.org/10.1371/journal.pone.0201848 . .

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Đikić, Jasmina
AU  - Vujnović, Ivana
AU  - Nacka-Aleksić, Mirjana
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3188
AB  - The study investigated strain specificities in age-related differences in CD8+ T cell-and microglial cell-mediated mechanisms implicated in induction/perpetuation and/or control of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in Albino Oxford (AO) and Dark Agouti (DA) rats exhibiting age-related changes in the susceptibility to EAE in the opposite direction (increase in relatively resistant AO rats vs decrease in DA rats). In the inductive phase of EAE, the greater number of fully differentiated effector CD8+ T lymphocytes was found in draining lymph nodes (dLNs) from aged rats of both strains than in strain-matched young rats, but this was particularly prominent in AO rats, which exhibited milder EAE of prolonged duration compared with their DA counterparts. Consistently, dLN IFN-gamma+ and IL-17+ CD8+ T cell counts were greater in aged AO than in DA rats. Additionally, the magnitudes of myelin basic protein (MBP)-induced rise in the frequency of IFN-gamma+ and IL-17+ CD8+ T cells (providing important help to neuroantigen-specific CD4+ T cells in EAE models characterized by clinically mild disease) were greater in dLN cell cultures from aged AO rats. Consistently, the magnitudes of MBP-induced rise in the frequency of both IFN-gamma+ and IL-17+ CD8+ T cells were greater in spinal cord mononuclear cell cultures from aged AO rats compared with their DA counterparts. Besides, with aging CD4+ CD25+ Foxp3+/CD8+ CD25+ Foxp3+ regulatory T cell ratio changed in spinal cord in the opposite direction. Consequently, in aged AO rats it was shifted towards CD8+ CD25+ Foxp3+ regulatory T cells (exhibiting lower suppressive capacity) when compared with DA rats. Moreover, the frequency of CX3CR1+ cells among microglia changed with aging and the disease development. In aged rats, in the effector phase of EAE it was lower in AO than in DA rats. This was accompanied by higher frequency of cells expressing IL-1 beta (whose down-regulation is central for CX3CR1-mediated neuroprotection), but lower that of phagocyting cells among microglia from aged AO compared their DA counterparts. The study indicates the control points linked with strain differences in age-related changes in EAE pathogenesis.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis
VL  - 101
SP  - 37
EP  - 53
DO  - 10.1016/j.exger.2017.11.002
ER  - 

@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Đikić, Jasmina and Vujnović, Ivana and Nacka-Aleksić, Mirjana and Bufan, Biljana and Arsenović-Ranin, Nevena and Kosec, Duško and Leposavić, Gordana",
year = "2018",
abstract = "The study investigated strain specificities in age-related differences in CD8+ T cell-and microglial cell-mediated mechanisms implicated in induction/perpetuation and/or control of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in Albino Oxford (AO) and Dark Agouti (DA) rats exhibiting age-related changes in the susceptibility to EAE in the opposite direction (increase in relatively resistant AO rats vs decrease in DA rats). In the inductive phase of EAE, the greater number of fully differentiated effector CD8+ T lymphocytes was found in draining lymph nodes (dLNs) from aged rats of both strains than in strain-matched young rats, but this was particularly prominent in AO rats, which exhibited milder EAE of prolonged duration compared with their DA counterparts. Consistently, dLN IFN-gamma+ and IL-17+ CD8+ T cell counts were greater in aged AO than in DA rats. Additionally, the magnitudes of myelin basic protein (MBP)-induced rise in the frequency of IFN-gamma+ and IL-17+ CD8+ T cells (providing important help to neuroantigen-specific CD4+ T cells in EAE models characterized by clinically mild disease) were greater in dLN cell cultures from aged AO rats. Consistently, the magnitudes of MBP-induced rise in the frequency of both IFN-gamma+ and IL-17+ CD8+ T cells were greater in spinal cord mononuclear cell cultures from aged AO rats compared with their DA counterparts. Besides, with aging CD4+ CD25+ Foxp3+/CD8+ CD25+ Foxp3+ regulatory T cell ratio changed in spinal cord in the opposite direction. Consequently, in aged AO rats it was shifted towards CD8+ CD25+ Foxp3+ regulatory T cells (exhibiting lower suppressive capacity) when compared with DA rats. Moreover, the frequency of CX3CR1+ cells among microglia changed with aging and the disease development. In aged rats, in the effector phase of EAE it was lower in AO than in DA rats. This was accompanied by higher frequency of cells expressing IL-1 beta (whose down-regulation is central for CX3CR1-mediated neuroprotection), but lower that of phagocyting cells among microglia from aged AO compared their DA counterparts. The study indicates the control points linked with strain differences in age-related changes in EAE pathogenesis.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis",
volume = "101",
pages = "37-53",
doi = "10.1016/j.exger.2017.11.002"
}

Stojić-Vukanić, Z., Pilipović, I., Đikić, J., Vujnović, I., Nacka-Aleksić, M., Bufan, B., Arsenović-Ranin, N., Kosec, D.,& Leposavić, G.. (2018). Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 101, 37-53.
https://doi.org/10.1016/j.exger.2017.11.002

Stojić-Vukanić Z, Pilipović I, Đikić J, Vujnović I, Nacka-Aleksić M, Bufan B, Arsenović-Ranin N, Kosec D, Leposavić G. Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis. in Experimental Gerontology. 2018;101:37-53.
doi:10.1016/j.exger.2017.11.002 .

Stojić-Vukanić, Zorica, Pilipović, Ivan, Đikić, Jasmina, Vujnović, Ivana, Nacka-Aleksić, Mirjana, Bufan, Biljana, Arsenović-Ranin, Nevena, Kosec, Duško, Leposavić, Gordana, "Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis" in Experimental Gerontology, 101 (2018):37-53,
https://doi.org/10.1016/j.exger.2017.11.002 . .

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Kotur-Stevuljević, Jelena
AU  - Nacka-Aleksić, Mirjana
AU  - Kosec, Duško
AU  - Vujnović, Ivana
AU  - Pilipović, Ivan
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3183
AB  - In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage.
PB  - Springer, New York
T2  - Molecular Neurobiology
T1  - Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action
VL  - 55
IS  - 5
SP  - 3755
EP  - 3774
DO  - 10.1007/s12035-017-0595-2
ER  - 

@article{
author = "Stojić-Vukanić, Zorica and Kotur-Stevuljević, Jelena and Nacka-Aleksić, Mirjana and Kosec, Duško and Vujnović, Ivana and Pilipović, Ivan and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2018",
abstract = "In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage.",
publisher = "Springer, New York",
journal = "Molecular Neurobiology",
title = "Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action",
volume = "55",
number = "5",
pages = "3755-3774",
doi = "10.1007/s12035-017-0595-2"
}

Stojić-Vukanić, Z., Kotur-Stevuljević, J., Nacka-Aleksić, M., Kosec, D., Vujnović, I., Pilipović, I., Dimitrijević, M.,& Leposavić, G.. (2018). Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action. in Molecular Neurobiology
Springer, New York., 55(5), 3755-3774.
https://doi.org/10.1007/s12035-017-0595-2

Stojić-Vukanić Z, Kotur-Stevuljević J, Nacka-Aleksić M, Kosec D, Vujnović I, Pilipović I, Dimitrijević M, Leposavić G. Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action. in Molecular Neurobiology. 2018;55(5):3755-3774.
doi:10.1007/s12035-017-0595-2 .

Stojić-Vukanić, Zorica, Kotur-Stevuljević, Jelena, Nacka-Aleksić, Mirjana, Kosec, Duško, Vujnović, Ivana, Pilipović, Ivan, Dimitrijević, Mirjana, Leposavić, Gordana, "Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action" in Molecular Neurobiology, 55, no. 5 (2018):3755-3774,
https://doi.org/10.1007/s12035-017-0595-2 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Lazarević-Macanović, Mirjana
AU  - Milovanović, Petar
AU  - Durić, Marija
AU  - Sopta, Jelena
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3220
AB  - Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-gamma + and IL-17 + IFN-gamma + T cells were found in female compared with male rat dLNs. However, the frequency of CD4 + CD25 + Foxp3 + T regulatory cells (Treg) did not differ between sexes. Thus, CD4 + Teff cells/Treg ratio, and IL-17 + T cells/Treg and IFN-gamma + T cells/Treg ratios were higher in female than in male rats, and among them was found lower frequency of PD-1+ cells. This suggested less efficient control of (auto)immune Th1/Th17 cell responses in female rat dLNs. On the contrary, the frequency of IL-4 + T cells was lower in female than in male rat dLNs. Consistently, the ratio of serum levels of collagen-specific IgG2a (IFN-gamma-dependent, with an important pathogenic role in CIA) and IgG1 (IL-4-dependent) was shifted towards IgG2a in female compared with male rats. As a whole, the study suggests that sexual dimorphism in the control of T cell activation/polarization could contribute to sex bias in the susceptibility to CIA. Moreover, the study advises the use of animals of both sexes in the preclinical testing of new drugs for rheumatoid arthritis.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Experimental and Molecular Pathology
T1  - Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease
VL  - 105
IS  - 1
SP  - 10
EP  - 22
DO  - 10.1016/j.yexmp.2018.05.007
ER  - 

@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Bufan, Biljana and Nacka-Aleksić, Mirjana and Lazarević-Macanović, Mirjana and Milovanović, Petar and Durić, Marija and Sopta, Jelena and Leposavić, Gordana",
year = "2018",
abstract = "Collagen-induced arthritis (CIA) is a frequently used animal model of rheumatoid arthritis, human autoimmune disease that exhibits clear sex bias in incidence and clinical course. Female Dark Agouti rats immunized for CIA showed also greater incidence and higher arthritic score than their male counterparts. The study investigated sex differences in mechanisms controlling the primary immune responses in draining lymph nodes (dLNs), as a factor contributing to this dimorphism. The higher frequencies of CD4 + CD25 + Foxp3- cells, presumably activated effector T (Teff) cells, and IL-17+, IFN-gamma + and IL-17 + IFN-gamma + T cells were found in female compared with male rat dLNs. However, the frequency of CD4 + CD25 + Foxp3 + T regulatory cells (Treg) did not differ between sexes. Thus, CD4 + Teff cells/Treg ratio, and IL-17 + T cells/Treg and IFN-gamma + T cells/Treg ratios were higher in female than in male rats, and among them was found lower frequency of PD-1+ cells. This suggested less efficient control of (auto)immune Th1/Th17 cell responses in female rat dLNs. On the contrary, the frequency of IL-4 + T cells was lower in female than in male rat dLNs. Consistently, the ratio of serum levels of collagen-specific IgG2a (IFN-gamma-dependent, with an important pathogenic role in CIA) and IgG1 (IL-4-dependent) was shifted towards IgG2a in female compared with male rats. As a whole, the study suggests that sexual dimorphism in the control of T cell activation/polarization could contribute to sex bias in the susceptibility to CIA. Moreover, the study advises the use of animals of both sexes in the preclinical testing of new drugs for rheumatoid arthritis.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Experimental and Molecular Pathology",
title = "Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease",
volume = "105",
number = "1",
pages = "10-22",
doi = "10.1016/j.yexmp.2018.05.007"
}

Dimitrijević, M., Arsenović-Ranin, N., Bufan, B., Nacka-Aleksić, M., Lazarević-Macanović, M., Milovanović, P., Durić, M., Sopta, J.,& Leposavić, G.. (2018). Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease. in Experimental and Molecular Pathology
Academic Press Inc Elsevier Science, San Diego., 105(1), 10-22.
https://doi.org/10.1016/j.yexmp.2018.05.007

Dimitrijević M, Arsenović-Ranin N, Bufan B, Nacka-Aleksić M, Lazarević-Macanović M, Milovanović P, Durić M, Sopta J, Leposavić G. Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease. in Experimental and Molecular Pathology. 2018;105(1):10-22.
doi:10.1016/j.yexmp.2018.05.007 .

Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Bufan, Biljana, Nacka-Aleksić, Mirjana, Lazarević-Macanović, Mirjana, Milovanović, Petar, Durić, Marija, Sopta, Jelena, Leposavić, Gordana, "Collagen-induced arthritis in Dark Agouti rats as a model for study of immunological sexual dimorphisms in the human disease" in Experimental and Molecular Pathology, 105, no. 1 (2018):10-22,
https://doi.org/10.1016/j.yexmp.2018.05.007 . .

TY  - JOUR
AU  - Petrović, Raisa
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Živković, Irena
AU  - Minić, Rajna
AU  - Radojević, Katarina
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3216
AB  - Aims: The study examined the influence of sex and mouse strain on germinal center (GC) reaction and antibody responses to seasonal split trivalent influenza vaccine (TIV). Main methods: C57BL/6 and BALB/c mice of both sexes were immunized with TIV and examined for specific antibody response by ELISA. Splenic T follicular regulatory (Tfr), T follicular helper (Tfh) and GC B cells are detected by flow cytometry. The proliferative response of splenocytes, and concentrations of IFN-gamma and IL-4 upon restimulation with vaccine antigens were examined by 7-AAD staining and ELISA, respectively. Key findings: BALB/c mice developed more robust IgG responses to vaccine type A antigens than their sexmatched C57BL/6 counterparts, while that to B antigen did not differ between strains. In both strains IgG responses against type A vaccine antigens were greater in females than in males. The greater IgG responses correlated with lower splenic Tfr/Tfh and Tfr/GC B cell ratios and greater vaccine antigen-specific proliferative responses of CD4+ and B cells in splenocyte cultures. In both mouse strains IgG2a(c)/IgG1 ratios were comparable between sexes, but lower in BALB/c than in C57BL/6 mice indicating a shift in Th1/Th2 balance towards Th2 response in BALB/c ones. Consistently, splenocytes from BALB/c mice produced more IL-4 and less IFN-gamma than those from C57BL/6 mice. Significance: The study indicated that magnitude of humoral response to influenza type A haemagglutinins depends on mouse strain and sex, and thereby set background for the vaccination strategies taking into account biological sex, and in a longterm perspective individual differences in immune reactivity.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Life Sciences
T1  - Mouse strain and sex as determinants of immune response to trivalent influenza vaccine
VL  - 207
SP  - 117
EP  - 126
DO  - 10.1016/j.lfs.2018.05.056
ER  - 

@article{
author = "Petrović, Raisa and Bufan, Biljana and Arsenović-Ranin, Nevena and Živković, Irena and Minić, Rajna and Radojević, Katarina and Leposavić, Gordana",
year = "2018",
abstract = "Aims: The study examined the influence of sex and mouse strain on germinal center (GC) reaction and antibody responses to seasonal split trivalent influenza vaccine (TIV). Main methods: C57BL/6 and BALB/c mice of both sexes were immunized with TIV and examined for specific antibody response by ELISA. Splenic T follicular regulatory (Tfr), T follicular helper (Tfh) and GC B cells are detected by flow cytometry. The proliferative response of splenocytes, and concentrations of IFN-gamma and IL-4 upon restimulation with vaccine antigens were examined by 7-AAD staining and ELISA, respectively. Key findings: BALB/c mice developed more robust IgG responses to vaccine type A antigens than their sexmatched C57BL/6 counterparts, while that to B antigen did not differ between strains. In both strains IgG responses against type A vaccine antigens were greater in females than in males. The greater IgG responses correlated with lower splenic Tfr/Tfh and Tfr/GC B cell ratios and greater vaccine antigen-specific proliferative responses of CD4+ and B cells in splenocyte cultures. In both mouse strains IgG2a(c)/IgG1 ratios were comparable between sexes, but lower in BALB/c than in C57BL/6 mice indicating a shift in Th1/Th2 balance towards Th2 response in BALB/c ones. Consistently, splenocytes from BALB/c mice produced more IL-4 and less IFN-gamma than those from C57BL/6 mice. Significance: The study indicated that magnitude of humoral response to influenza type A haemagglutinins depends on mouse strain and sex, and thereby set background for the vaccination strategies taking into account biological sex, and in a longterm perspective individual differences in immune reactivity.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Life Sciences",
title = "Mouse strain and sex as determinants of immune response to trivalent influenza vaccine",
volume = "207",
pages = "117-126",
doi = "10.1016/j.lfs.2018.05.056"
}

Petrović, R., Bufan, B., Arsenović-Ranin, N., Živković, I., Minić, R., Radojević, K.,& Leposavić, G.. (2018). Mouse strain and sex as determinants of immune response to trivalent influenza vaccine. in Life Sciences
Pergamon-Elsevier Science Ltd, Oxford., 207, 117-126.
https://doi.org/10.1016/j.lfs.2018.05.056

Petrović R, Bufan B, Arsenović-Ranin N, Živković I, Minić R, Radojević K, Leposavić G. Mouse strain and sex as determinants of immune response to trivalent influenza vaccine. in Life Sciences. 2018;207:117-126.
doi:10.1016/j.lfs.2018.05.056 .

Petrović, Raisa, Bufan, Biljana, Arsenović-Ranin, Nevena, Živković, Irena, Minić, Rajna, Radojević, Katarina, Leposavić, Gordana, "Mouse strain and sex as determinants of immune response to trivalent influenza vaccine" in Life Sciences, 207 (2018):117-126,
https://doi.org/10.1016/j.lfs.2018.05.056 . .

TY  - JOUR
AU  - Živković, Irena
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Petrusić, Vladimir
AU  - Minić, Rajna
AU  - Bufan, Biljana
AU  - Popović, Olga
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3160
AB  - The study explored influence of biological sex on development of humoral immune response to seasonal trivalent whole inactivated virus (WIV) and split virus (SV) influenza vaccines in outbred Swiss mouse model. To this end, mice of both sexes were immunized with WIV (WIV mice) and SV vaccines (SV mice) and examined for specific antibody response. Irrespective of sex, total IgG and neutralizing antibody responses to distinct virus strains were weaker in SV than in WIV mice. In WIV mice of both sexes, irrespective of strain specificity, IgG isotype response was dominated by IgG2a antibodies, while in SV mice nearly equal representation of IgG2a and IgG1 antibodies was found. The analyses of sex differences showed higher titers of H1N1-specific and both H1N1- and H3N2-specific total IgG and neutralizing antibodies in female WIV and SV mice, respectively. Additionally, sexual dimorphism in IgG subclass profile depended on vaccine type. Specifically, compared with males, in females WIV shifted IgG2a/IgG1 antibody ratio towards IgG2a isotype on the account of weaker IgG1 response, whereas in SV mice, irrespective of virus strain, IgG2a and IgG1 isotypes were equally represented in both sexes. These findings indicate the vaccine type-dependent sex bias in antibody response to inactivated influenza vaccines.
PB  - Academic Press Ltd- Elsevier Science Ltd, London
T2  - Biologicals
T1  - Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type
VL  - 52
SP  - 18
EP  - 24
DO  - 10.1016/j.biologicals.2018.01.007
ER  - 

@article{
author = "Živković, Irena and Petrović, Raisa and Arsenović-Ranin, Nevena and Petrusić, Vladimir and Minić, Rajna and Bufan, Biljana and Popović, Olga and Leposavić, Gordana",
year = "2018",
abstract = "The study explored influence of biological sex on development of humoral immune response to seasonal trivalent whole inactivated virus (WIV) and split virus (SV) influenza vaccines in outbred Swiss mouse model. To this end, mice of both sexes were immunized with WIV (WIV mice) and SV vaccines (SV mice) and examined for specific antibody response. Irrespective of sex, total IgG and neutralizing antibody responses to distinct virus strains were weaker in SV than in WIV mice. In WIV mice of both sexes, irrespective of strain specificity, IgG isotype response was dominated by IgG2a antibodies, while in SV mice nearly equal representation of IgG2a and IgG1 antibodies was found. The analyses of sex differences showed higher titers of H1N1-specific and both H1N1- and H3N2-specific total IgG and neutralizing antibodies in female WIV and SV mice, respectively. Additionally, sexual dimorphism in IgG subclass profile depended on vaccine type. Specifically, compared with males, in females WIV shifted IgG2a/IgG1 antibody ratio towards IgG2a isotype on the account of weaker IgG1 response, whereas in SV mice, irrespective of virus strain, IgG2a and IgG1 isotypes were equally represented in both sexes. These findings indicate the vaccine type-dependent sex bias in antibody response to inactivated influenza vaccines.",
publisher = "Academic Press Ltd- Elsevier Science Ltd, London",
journal = "Biologicals",
title = "Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type",
volume = "52",
pages = "18-24",
doi = "10.1016/j.biologicals.2018.01.007"
}

Živković, I., Petrović, R., Arsenović-Ranin, N., Petrusić, V., Minić, R., Bufan, B., Popović, O.,& Leposavić, G.. (2018). Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type. in Biologicals
Academic Press Ltd- Elsevier Science Ltd, London., 52, 18-24.
https://doi.org/10.1016/j.biologicals.2018.01.007

Živković I, Petrović R, Arsenović-Ranin N, Petrusić V, Minić R, Bufan B, Popović O, Leposavić G. Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type. in Biologicals. 2018;52:18-24.
doi:10.1016/j.biologicals.2018.01.007 .

Živković, Irena, Petrović, Raisa, Arsenović-Ranin, Nevena, Petrusić, Vladimir, Minić, Rajna, Bufan, Biljana, Popović, Olga, Leposavić, Gordana, "Sex bias in mouse humoral immune response to influenza vaccine depends on the vaccine type" in Biologicals, 52 (2018):18-24,
https://doi.org/10.1016/j.biologicals.2018.01.007 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pilipović, Ivan
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3193
AB  - The thymus is sexually differentiated organ providing microenvironment for T-cell precursor differentiation/maturation in the major histocompatibility complex-restricted self-tolerant T cells. With increasing age, the thymus undergoes involution leading to the decline in efficacy of thymopoiesis. Noradrenaline from thymic nerve fibers and "(nor) adrenergic" cells is involved in the regulation of thymopoiesis. In rodents, noradrenaline concentration in thymus and adrenoceptor (AR) expression on thymic cells depend on sex and age. These differences are suggested to be implicated in the development of sexual diergism and the age-related decline in thymopoiesis. The programming of both thymic sexual differentiation and its involution occurs during the critical early perinatal period and may be reprogrammed during peripubertal development. The thymic (re) programming is critically dependent on circulating levels of gonadal steroids. Although the underlying molecular mechanisms have not yet been elucidated fully, it is assumed that the gonadal steroid action during the critical perinatal/peripubertal developmental periods leads to long-lasting changes in the efficacy of thymopoiesis partly through (re) programming of "(nor) adrenergic" cell networks and AR expression on thymic cells.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Endocrinology
T1  - Intrinsic and Extrinsic Thymic Adrenergic Networks: Sex Steroid-Dependent Plasticity
VL  - 9
DO  - 10.3389/fendo.2018.00013
ER  - 

@article{
author = "Leposavić, Gordana and Pilipović, Ivan",
year = "2018",
abstract = "The thymus is sexually differentiated organ providing microenvironment for T-cell precursor differentiation/maturation in the major histocompatibility complex-restricted self-tolerant T cells. With increasing age, the thymus undergoes involution leading to the decline in efficacy of thymopoiesis. Noradrenaline from thymic nerve fibers and "(nor) adrenergic" cells is involved in the regulation of thymopoiesis. In rodents, noradrenaline concentration in thymus and adrenoceptor (AR) expression on thymic cells depend on sex and age. These differences are suggested to be implicated in the development of sexual diergism and the age-related decline in thymopoiesis. The programming of both thymic sexual differentiation and its involution occurs during the critical early perinatal period and may be reprogrammed during peripubertal development. The thymic (re) programming is critically dependent on circulating levels of gonadal steroids. Although the underlying molecular mechanisms have not yet been elucidated fully, it is assumed that the gonadal steroid action during the critical perinatal/peripubertal developmental periods leads to long-lasting changes in the efficacy of thymopoiesis partly through (re) programming of "(nor) adrenergic" cell networks and AR expression on thymic cells.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Endocrinology",
title = "Intrinsic and Extrinsic Thymic Adrenergic Networks: Sex Steroid-Dependent Plasticity",
volume = "9",
doi = "10.3389/fendo.2018.00013"
}

Leposavić, G.,& Pilipović, I.. (2018). Intrinsic and Extrinsic Thymic Adrenergic Networks: Sex Steroid-Dependent Plasticity. in Frontiers in Endocrinology
Frontiers Media Sa, Lausanne., 9.
https://doi.org/10.3389/fendo.2018.00013

Leposavić G, Pilipović I. Intrinsic and Extrinsic Thymic Adrenergic Networks: Sex Steroid-Dependent Plasticity. in Frontiers in Endocrinology. 2018;9.
doi:10.3389/fendo.2018.00013 .

Leposavić, Gordana, Pilipović, Ivan, "Intrinsic and Extrinsic Thymic Adrenergic Networks: Sex Steroid-Dependent Plasticity" in Frontiers in Endocrinology, 9 (2018),
https://doi.org/10.3389/fendo.2018.00013 . .

TY  - JOUR
AU  - Stanojević, Stanislava
AU  - Blagojević, Veljko
AU  - Curuvija, Ivana
AU  - Veljović, Katarina
AU  - Soković-Bajić, Svetlana
AU  - Kotur-Stevuljević, Jelena
AU  - Bogdanović, Andrija
AU  - Petrović, Raisa
AU  - Vujnović, Ivana
AU  - Kovačević-Jovanović, Vesna
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3091
AB  - The current study investigated a potential modulating effect of orally applied Lactobacillus rhamnosus 64 (LB64) during the early postnatal period (day of life: similar to 3-30), during young adult period (day of life: 31-70) or throughout experiment, on parameters of trinitrobenzenesulfonic acid (TNBS)-induced colitis in adult rats. Treatment with LB64 during early postnatal, but not during young adult period reduced clinical damage score, neutrophil and macrophage infiltration into colon, the level of cytokine and myeloperoxidase (MPO) activity, but had no influence on other parameters of oxidative damage. Early postnatal treatment with LB64 also increased the diversity of fecal Bifidobacteria and Eubacteria, and improved maturation of ileal villi in 30-days old rats. When LB64 is applied during a critical period early in life, it affects immune system functioning of adults, probably by interactions with the mucosal immune system of the gastrointestinal tract that provides immune system maturation and shapes the overall immune response.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Functional Foods
T1  - Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis
VL  - 48
SP  - 92
EP  - 105
DO  - 10.1016/j.jff.2018.07.014
ER  - 

@article{
author = "Stanojević, Stanislava and Blagojević, Veljko and Curuvija, Ivana and Veljović, Katarina and Soković-Bajić, Svetlana and Kotur-Stevuljević, Jelena and Bogdanović, Andrija and Petrović, Raisa and Vujnović, Ivana and Kovačević-Jovanović, Vesna",
year = "2018",
abstract = "The current study investigated a potential modulating effect of orally applied Lactobacillus rhamnosus 64 (LB64) during the early postnatal period (day of life: similar to 3-30), during young adult period (day of life: 31-70) or throughout experiment, on parameters of trinitrobenzenesulfonic acid (TNBS)-induced colitis in adult rats. Treatment with LB64 during early postnatal, but not during young adult period reduced clinical damage score, neutrophil and macrophage infiltration into colon, the level of cytokine and myeloperoxidase (MPO) activity, but had no influence on other parameters of oxidative damage. Early postnatal treatment with LB64 also increased the diversity of fecal Bifidobacteria and Eubacteria, and improved maturation of ileal villi in 30-days old rats. When LB64 is applied during a critical period early in life, it affects immune system functioning of adults, probably by interactions with the mucosal immune system of the gastrointestinal tract that provides immune system maturation and shapes the overall immune response.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Functional Foods",
title = "Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis",
volume = "48",
pages = "92-105",
doi = "10.1016/j.jff.2018.07.014"
}

Stanojević, S., Blagojević, V., Curuvija, I., Veljović, K., Soković-Bajić, S., Kotur-Stevuljević, J., Bogdanović, A., Petrović, R., Vujnović, I.,& Kovačević-Jovanović, V.. (2018). Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis. in Journal of Functional Foods
Elsevier Science BV, Amsterdam., 48, 92-105.
https://doi.org/10.1016/j.jff.2018.07.014

Stanojević S, Blagojević V, Curuvija I, Veljović K, Soković-Bajić S, Kotur-Stevuljević J, Bogdanović A, Petrović R, Vujnović I, Kovačević-Jovanović V. Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis. in Journal of Functional Foods. 2018;48:92-105.
doi:10.1016/j.jff.2018.07.014 .

Stanojević, Stanislava, Blagojević, Veljko, Curuvija, Ivana, Veljović, Katarina, Soković-Bajić, Svetlana, Kotur-Stevuljević, Jelena, Bogdanović, Andrija, Petrović, Raisa, Vujnović, Ivana, Kovačević-Jovanović, Vesna, "Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis" in Journal of Functional Foods, 48 (2018):92-105,
https://doi.org/10.1016/j.jff.2018.07.014 . .