TY  - CONF
AU  - Panić, Marko
AU  - Prijić, Ivana
AU  - Simić, Mihajlo
AU  - Lukić, Ivana
AU  - Petrušić, Marija
AU  - Živković, Irena
AU  - Kojić, Milan
PY  - 2024
UR  - http://intor.torlakinstitut.com/handle/123456789/876
AB  - Tetanus toxin, a highly potent neurotoxin produced by Clostridium tetani, is the primary agent responsible for causing tetanus. This serious, potentially fatal disease can be effectively prevented through vaccination. Thanks to successful vaccination campaigns, tetanus has become exceedingly rare in both developed and most developing countries. However, the widespread presence of C. tetani spores in the environment means that tetanus cannot be completely eradicated, underscoring the ongoing need for vaccination. Traditionally, tetanus vaccines are produced by cultivating C. tetani, extracting a crude form of the tetanus toxin, and then chemically inactivating it for use in immunization. This method has proven clinically effective and is in widespread use. A challenge with this approach, however, is that the vaccine contains hundreds of various C. tetani proteins, with the active component making up only a variable and small fraction of the overall vaccine mass. To improve the current tetanus vaccine, there is potential in the recombinant production of a genetically inactivated tetanus vaccine. Prior studies have demonstrated the feasibility of engineering the full-length tetanus toxin in E. coli, and our current work builds on this foundation. We have successfully cloned the complete tetanus toxin open reading frame into the pMAL expression vector. This step was followed by the creation of a genetically inactivated protein, achieved through standard site-directed mutagenesis which altered 8 critical amino acid residues. These mutations have been confirmed via sequencing, ensuring that the toxin is genetically inactivated and thus does not require chemical inactivation for vaccine production. Our present focus is on optimizing the expression of this protein in E. coli. Following this, we intend to conduct thorough assessments of the biochemical and immunological properties of the recombinant tetanus toxin. This research represents a promising avenue towards enhancing the efficacy and specificity of tetanus vaccines, potentially improving global health outcomes.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
T1  - Exploring E. coli-based expression of genetically inactivated tetanus toxin for vaccine development
EP  - 113
SP  - 113
UR  - https://hdl.handle.net/21.15107/rcub_intor_876
ER  - 

@conference{
author = "Panić, Marko and Prijić, Ivana and Simić, Mihajlo and Lukić, Ivana and Petrušić, Marija and Živković, Irena and Kojić, Milan",
year = "2024",
abstract = "Tetanus toxin, a highly potent neurotoxin produced by Clostridium tetani, is the primary agent responsible for causing tetanus. This serious, potentially fatal disease can be effectively prevented through vaccination. Thanks to successful vaccination campaigns, tetanus has become exceedingly rare in both developed and most developing countries. However, the widespread presence of C. tetani spores in the environment means that tetanus cannot be completely eradicated, underscoring the ongoing need for vaccination. Traditionally, tetanus vaccines are produced by cultivating C. tetani, extracting a crude form of the tetanus toxin, and then chemically inactivating it for use in immunization. This method has proven clinically effective and is in widespread use. A challenge with this approach, however, is that the vaccine contains hundreds of various C. tetani proteins, with the active component making up only a variable and small fraction of the overall vaccine mass. To improve the current tetanus vaccine, there is potential in the recombinant production of a genetically inactivated tetanus vaccine. Prior studies have demonstrated the feasibility of engineering the full-length tetanus toxin in E. coli, and our current work builds on this foundation. We have successfully cloned the complete tetanus toxin open reading frame into the pMAL expression vector. This step was followed by the creation of a genetically inactivated protein, achieved through standard site-directed mutagenesis which altered 8 critical amino acid residues. These mutations have been confirmed via sequencing, ensuring that the toxin is genetically inactivated and thus does not require chemical inactivation for vaccine production. Our present focus is on optimizing the expression of this protein in E. coli. Following this, we intend to conduct thorough assessments of the biochemical and immunological properties of the recombinant tetanus toxin. This research represents a promising avenue towards enhancing the efficacy and specificity of tetanus vaccines, potentially improving global health outcomes.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april",
title = "Exploring E. coli-based expression of genetically inactivated tetanus toxin for vaccine development",
pages = "113-113",
url = "https://hdl.handle.net/21.15107/rcub_intor_876"
}

Panić, M., Prijić, I., Simić, M., Lukić, I., Petrušić, M., Živković, I.,& Kojić, M.. (2024). Exploring E. coli-based expression of genetically inactivated tetanus toxin for vaccine development. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
Serbian Society for Microbiology., 113-113.
https://hdl.handle.net/21.15107/rcub_intor_876

Panić M, Prijić I, Simić M, Lukić I, Petrušić M, Živković I, Kojić M. Exploring E. coli-based expression of genetically inactivated tetanus toxin for vaccine development. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april. 2024;:113-113.
https://hdl.handle.net/21.15107/rcub_intor_876 .

Panić, Marko, Prijić, Ivana, Simić, Mihajlo, Lukić, Ivana, Petrušić, Marija, Živković, Irena, Kojić, Milan, "Exploring E. coli-based expression of genetically inactivated tetanus toxin for vaccine development" in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april (2024):113-113,
https://hdl.handle.net/21.15107/rcub_intor_876 .

TY  - CONF
AU  - Minić, Rajna
AU  - Đorđević, Brižita
AU  - Michaličkova, Danica
AU  - Živković, Irena
AU  - Živančević Simonović, Snežana
AU  - Ilić, Vesna
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1407
UR  - http://intor.torlakinstitut.com/handle/123456789/862
AB  - U ovom izlaganju biće predstavljeni naši dosadašnji rezultati na temu antimikrobnih antitela kod profesionalnih sportista, odraslih osoba koje se ne bave profesionalno sportom; promene nivoa antibakterijskih antitela pri starenju; poređenje specifičnosti serumskih i salivarnih IgA antitela kod mladih odraslih osoba, kao i nivoi ukupnih i antibakterijskih antitela u Covid-19 virusnoj infekciji i u sepsi. Nivoi i titri antimikrobnih antitela različitih klasa i potklasa određivani su ELISA testom iz uzoraka seruma, plazme ili salive. Ispitivano je vezivanje za izolovane antigene mikroorganizama (lipopolisaharid, peptidoglikan i zimozan) i za cele mikroorganizme, različitih vrsta i sojeva. Vezivanje prečišćenog salivarnog IgA za mikroorganizme praćeno je i protočnom citometrijom. Od rezultata izdvajamo da izlaganje fizičkom naporu visokog intenziteta dovodi do promena na nivou antibakterijskih antitela, i to u pravcu sveobuhvatnijeg prepoznavanja lipopolisaharida1. Suplementacija profesionalnih sportista određenim probioticima dovodi do održanja nivoa ukupnih salivarnih i serumskih IgA antitela, kao i IgG antitela specifičnih prema Enterococcus faecalis, koja su u ovoj populaciji pokazala sezonsku varijaciju. Pri starenju dolazi do smanjenja nivoa antipneumokoknih antitela i to zavisno od pola, pa su stariji mukarci naročito pogođeni ovim smanjenjem3. Salivarna IgA antitela razlikuju se po specifičnosti od serumskih IgA antitela i pružaju nespecifičnu zaštitu. Poređenje pacijenata sa sepsom, hospitalizovanih Covid-19 pacijenta i starosnih kontrola pokazalo je brojne razlike u nivoima kako ukupnih, tako i antibakterijskih antitela. Nivoi antibakterijskih antitela kod pacijentata koji nisu preživeli bili su niži nego kod onih koji su preživeli, što potvrđuje značaj ovih anititela za preživljavanje sepse.
PB  - Beograd: Srpska akademija nauka i umetnosti, Odeljenje medicinskih nauka SANU, Odbor za imunologiju i alergologiju i Društvo imunologa Srbije
C3  - Naučni skup Svetski dan imunologije, 27. april 2023. godine Svečana sala SANU - Knjiga sažetaka
T1  - Antimikrobna antitela u fiziološkim i patološkim stanjima
UR  - https://hdl.handle.net/21.15107/rcub_intor_862
ER  - 

@conference{
author = "Minić, Rajna and Đorđević, Brižita and Michaličkova, Danica and Živković, Irena and Živančević Simonović, Snežana and Ilić, Vesna",
year = "2023",
abstract = "U ovom izlaganju biće predstavljeni naši dosadašnji rezultati na temu antimikrobnih antitela kod profesionalnih sportista, odraslih osoba koje se ne bave profesionalno sportom; promene nivoa antibakterijskih antitela pri starenju; poređenje specifičnosti serumskih i salivarnih IgA antitela kod mladih odraslih osoba, kao i nivoi ukupnih i antibakterijskih antitela u Covid-19 virusnoj infekciji i u sepsi. Nivoi i titri antimikrobnih antitela različitih klasa i potklasa određivani su ELISA testom iz uzoraka seruma, plazme ili salive. Ispitivano je vezivanje za izolovane antigene mikroorganizama (lipopolisaharid, peptidoglikan i zimozan) i za cele mikroorganizme, različitih vrsta i sojeva. Vezivanje prečišćenog salivarnog IgA za mikroorganizme praćeno je i protočnom citometrijom. Od rezultata izdvajamo da izlaganje fizičkom naporu visokog intenziteta dovodi do promena na nivou antibakterijskih antitela, i to u pravcu sveobuhvatnijeg prepoznavanja lipopolisaharida1. Suplementacija profesionalnih sportista određenim probioticima dovodi do održanja nivoa ukupnih salivarnih i serumskih IgA antitela, kao i IgG antitela specifičnih prema Enterococcus faecalis, koja su u ovoj populaciji pokazala sezonsku varijaciju. Pri starenju dolazi do smanjenja nivoa antipneumokoknih antitela i to zavisno od pola, pa su stariji mukarci naročito pogođeni ovim smanjenjem3. Salivarna IgA antitela razlikuju se po specifičnosti od serumskih IgA antitela i pružaju nespecifičnu zaštitu. Poređenje pacijenata sa sepsom, hospitalizovanih Covid-19 pacijenta i starosnih kontrola pokazalo je brojne razlike u nivoima kako ukupnih, tako i antibakterijskih antitela. Nivoi antibakterijskih antitela kod pacijentata koji nisu preživeli bili su niži nego kod onih koji su preživeli, što potvrđuje značaj ovih anititela za preživljavanje sepse.",
publisher = "Beograd: Srpska akademija nauka i umetnosti, Odeljenje medicinskih nauka SANU, Odbor za imunologiju i alergologiju i Društvo imunologa Srbije",
journal = "Naučni skup Svetski dan imunologije, 27. april 2023. godine Svečana sala SANU - Knjiga sažetaka",
title = "Antimikrobna antitela u fiziološkim i patološkim stanjima",
url = "https://hdl.handle.net/21.15107/rcub_intor_862"
}

Minić, R., Đorđević, B., Michaličkova, D., Živković, I., Živančević Simonović, S.,& Ilić, V.. (2023). Antimikrobna antitela u fiziološkim i patološkim stanjima. in Naučni skup Svetski dan imunologije, 27. april 2023. godine Svečana sala SANU - Knjiga sažetaka
Beograd: Srpska akademija nauka i umetnosti, Odeljenje medicinskih nauka SANU, Odbor za imunologiju i alergologiju i Društvo imunologa Srbije..
https://hdl.handle.net/21.15107/rcub_intor_862

Minić R, Đorđević B, Michaličkova D, Živković I, Živančević Simonović S, Ilić V. Antimikrobna antitela u fiziološkim i patološkim stanjima. in Naučni skup Svetski dan imunologije, 27. april 2023. godine Svečana sala SANU - Knjiga sažetaka. 2023;.
https://hdl.handle.net/21.15107/rcub_intor_862 .

Minić, Rajna, Đorđević, Brižita, Michaličkova, Danica, Živković, Irena, Živančević Simonović, Snežana, Ilić, Vesna, "Antimikrobna antitela u fiziološkim i patološkim stanjima" in Naučni skup Svetski dan imunologije, 27. april 2023. godine Svečana sala SANU - Knjiga sažetaka (2023),
https://hdl.handle.net/21.15107/rcub_intor_862 .

TY  - CONF
AU  - Ivanović, Saša
AU  - Ćupić, Vitomir
AU  - Živković, Irena
AU  - Milovanović, Vladimir
AU  - Ćupić Miladinović, Dejana
AU  - Borozan, Sunčica
PY  - 2023
UR  - http://intor.torlakinstitut.com/handle/123456789/845
AB  - Poskok (Vipera ammodytes) predstavlja najzastupljeniju zmiju otrovnicu u Srbiji i na Balkanu, kako po brojnosti tako i po arealu rasprostranjenosti. U poređenju sa venomima ostalih otrovnica iz familije Viperidae na Balkanu, toksičnost venoma poskoka je najveća. Neurotoksičnost sirovog venoma poskoka smo ispitivali u in vitro uslovima na osnovu kontrakcija preparata dijafragme izazvanih poljnom električnom stimulacijom i aktivnosti enzima: acetilholinesteraze (AChE) i ukupnih ATP-aza u dijafragmi.Formirano je 5 grupa pacova (n=5): kontrola (dijafragma bez venoma), dijafragma sa venomom, dijafragma sa smešom venom/antivenom („Viekvin“, Torlak, Srbija) u odnosima 1:2, 1:10 i 1:20 (m/m). Kontrakcije dijafragme su opale na 50% kontrolnih kontrakcija: pod uticajem venoma za 62,00±2,31minuta, a sa smešom venom/antivenom 1:2 za 78,50±7,51 minuta, 1:10 za 150,00±17,32 minuta, 1:20 za 307,50±2,89 minuta. Statistička razlika (p0,05) pod dejstvom venoma. Venom inhibira aktivnost ukupnih ATP-aza dijafragme za 51,81% u odnosu na kontrolu. Venom poskoka ne deluje na AChE i nikotinske receptore u neuro-mišićnoj sinapsi dijafragme, već narušava energetski metabolizam mitohondrija.
AB  - Vipera ammodytes is the most common venomous snake in Serbia and the Balkans, both in terms of numbers and area of distribution. Compared to the venoms of other poisonous snakes from the family Viperidae in the Balkans, the toxicity of the V. ammodytes venom is the highest. We investigated the neurotoxicity of crude venom in vitro using contractions of the diaphragm preparation induced by electric field stimulation and enzyme activity: acetylcholinesterase (AChE) and total ATPases in the diaphragm. Five groups of rats were formed (n=5): control (diaphragm without venom), diaphragmwith venom, diaphragm with mixture of venom/antivenom ("Viekvin", Torlak, Serbia) in the ratio 1:2, 1:10 and 1:20 (m/m). Diaphragmatic contractions decreased to 50% of control contractions: under the influence of venom for 62.00±2.31 minutes, and with venom/antivenom mixture 1:2 for 78.50±7.51 minutes, 1:10 for 150.00±17.32 minutes, 1:20 for 307.50±2.89 minutes. A statistical difference (p 0.05) under the influence of the venom. Venom inhibits the total ATPases activity of the diaphragm by 51.81% compared with control.The venom of V. ammodytes does not act on AChE and nicotinic receptors in the neuromuscular synapse of the diaphragm, but interferes with mitochondrial energy metabolism.
PB  - Belgrade : Serbian Society of Toxicology
C3  - 13th International Congress of the Serbian Society of Toxicology and 1st TOXSEE Regional Conference, belgrade, 10 - 12 May, 2023
T1  - Neurotoksično dejstvo venoma Vipera ammodytes na modelu izolovane dijafragme pacova
T1  - Neurotoxic effect of Vipera ammodytes venom on the rat isolated diaphragm model
EP  - 108
SP  - 107
UR  - https://hdl.handle.net/21.15107/rcub_intor_845
ER  - 

@conference{
author = "Ivanović, Saša and Ćupić, Vitomir and Živković, Irena and Milovanović, Vladimir and Ćupić Miladinović, Dejana and Borozan, Sunčica",
year = "2023",
abstract = "Poskok (Vipera ammodytes) predstavlja najzastupljeniju zmiju otrovnicu u Srbiji i na Balkanu, kako po brojnosti tako i po arealu rasprostranjenosti. U poređenju sa venomima ostalih otrovnica iz familije Viperidae na Balkanu, toksičnost venoma poskoka je najveća. Neurotoksičnost sirovog venoma poskoka smo ispitivali u in vitro uslovima na osnovu kontrakcija preparata dijafragme izazvanih poljnom električnom stimulacijom i aktivnosti enzima: acetilholinesteraze (AChE) i ukupnih ATP-aza u dijafragmi.Formirano je 5 grupa pacova (n=5): kontrola (dijafragma bez venoma), dijafragma sa venomom, dijafragma sa smešom venom/antivenom („Viekvin“, Torlak, Srbija) u odnosima 1:2, 1:10 i 1:20 (m/m). Kontrakcije dijafragme su opale na 50% kontrolnih kontrakcija: pod uticajem venoma za 62,00±2,31minuta, a sa smešom venom/antivenom 1:2 za 78,50±7,51 minuta, 1:10 za 150,00±17,32 minuta, 1:20 za 307,50±2,89 minuta. Statistička razlika (p0,05) pod dejstvom venoma. Venom inhibira aktivnost ukupnih ATP-aza dijafragme za 51,81% u odnosu na kontrolu. Venom poskoka ne deluje na AChE i nikotinske receptore u neuro-mišićnoj sinapsi dijafragme, već narušava energetski metabolizam mitohondrija., Vipera ammodytes is the most common venomous snake in Serbia and the Balkans, both in terms of numbers and area of distribution. Compared to the venoms of other poisonous snakes from the family Viperidae in the Balkans, the toxicity of the V. ammodytes venom is the highest. We investigated the neurotoxicity of crude venom in vitro using contractions of the diaphragm preparation induced by electric field stimulation and enzyme activity: acetylcholinesterase (AChE) and total ATPases in the diaphragm. Five groups of rats were formed (n=5): control (diaphragm without venom), diaphragmwith venom, diaphragm with mixture of venom/antivenom ("Viekvin", Torlak, Serbia) in the ratio 1:2, 1:10 and 1:20 (m/m). Diaphragmatic contractions decreased to 50% of control contractions: under the influence of venom for 62.00±2.31 minutes, and with venom/antivenom mixture 1:2 for 78.50±7.51 minutes, 1:10 for 150.00±17.32 minutes, 1:20 for 307.50±2.89 minutes. A statistical difference (p 0.05) under the influence of the venom. Venom inhibits the total ATPases activity of the diaphragm by 51.81% compared with control.The venom of V. ammodytes does not act on AChE and nicotinic receptors in the neuromuscular synapse of the diaphragm, but interferes with mitochondrial energy metabolism.",
publisher = "Belgrade : Serbian Society of Toxicology",
journal = "13th International Congress of the Serbian Society of Toxicology and 1st TOXSEE Regional Conference, belgrade, 10 - 12 May, 2023",
title = "Neurotoksično dejstvo venoma Vipera ammodytes na modelu izolovane dijafragme pacova, Neurotoxic effect of Vipera ammodytes venom on the rat isolated diaphragm model",
pages = "108-107",
url = "https://hdl.handle.net/21.15107/rcub_intor_845"
}

Ivanović, S., Ćupić, V., Živković, I., Milovanović, V., Ćupić Miladinović, D.,& Borozan, S.. (2023). Neurotoksično dejstvo venoma Vipera ammodytes na modelu izolovane dijafragme pacova. in 13th International Congress of the Serbian Society of Toxicology and 1st TOXSEE Regional Conference, belgrade, 10 - 12 May, 2023
Belgrade : Serbian Society of Toxicology., 107-108.
https://hdl.handle.net/21.15107/rcub_intor_845

Ivanović S, Ćupić V, Živković I, Milovanović V, Ćupić Miladinović D, Borozan S. Neurotoksično dejstvo venoma Vipera ammodytes na modelu izolovane dijafragme pacova. in 13th International Congress of the Serbian Society of Toxicology and 1st TOXSEE Regional Conference, belgrade, 10 - 12 May, 2023. 2023;:107-108.
https://hdl.handle.net/21.15107/rcub_intor_845 .

Ivanović, Saša, Ćupić, Vitomir, Živković, Irena, Milovanović, Vladimir, Ćupić Miladinović, Dejana, Borozan, Sunčica, "Neurotoksično dejstvo venoma Vipera ammodytes na modelu izolovane dijafragme pacova" in 13th International Congress of the Serbian Society of Toxicology and 1st TOXSEE Regional Conference, belgrade, 10 - 12 May, 2023 (2023):107-108,
https://hdl.handle.net/21.15107/rcub_intor_845 .

TY  - JOUR
AU  - Ivanović, Saša R.
AU  - Borozan, Nevena
AU  - Ćupić Miladinović, Dejana
AU  - Živković, Irena
AU  - Borozan, Sunčica
PY  - 2023
UR  - http://intor.torlakinstitut.com/handle/123456789/658
AB  - Diazinon is an organophosphate pesticide (OP) that has significant potential for accidental and intentional poisoning of wildlife, domestic animals and humans. The aim of the study is to investigate the correlation between cholinesterase activity and oxidative stress parameters in liver and diaphragm by continuous monitoring as a function of time during prolonged use of diazinon. Wistar rats were treated orally with diazinon (55 mg/kg/day): 7, 14, 21 and 28 days. At the end of each period, blood, liver and diaphragm were collected to examine cholinesterase activity and enzymatic/non-enzymatic oxidative stress parameters: superoxide dismutase 1 (SOD1), catalase (CAT), thiobarbituric acid substances (TBARS), protein carbonyl groups. In all four time periods, there was a significant change in acetylcholinesterase (AChE) in erythrocytes and butyrylcholinesterase (BuChE) in blood plasma, CAT in liver and diaphragm and SOD1 in diaphragm. Parameters significantly altered during the cholinergic crisis included: cholinesterases and TBARS in liver and diaphragm and partially SOD1 in liver. Protein carbonyl groups in liver and diaphragm were significantly altered outside the cholinergic crisis. In the liver, there was a very strong negative correlation between BuChE and TBARS in all four time periods and BuChE and CAT on day 7. In the diaphragm, a very strong negative correlation was found between AChE and TBARS at days 7 and 14, and a very strong positive correlation between AChE and SOD1 at days 14, 21 and 28. A better understanding of the relationship between cholinergic overstimulation and oxidative stress may help to better assess health status in prolonged OPs intoxication.
PB  - Elsevier
T2  - Toxicology and Applied Pharmacology
T1  - The relationship between the cholinergic mechanism of toxicity and oxidative stress in rats during subacute diazinon poisoning
SP  - 116598
VL  - 473
DO  - 10.1016/j.taap.2023.116598
ER  - 

@article{
author = "Ivanović, Saša R. and Borozan, Nevena and Ćupić Miladinović, Dejana and Živković, Irena and Borozan, Sunčica",
year = "2023",
abstract = "Diazinon is an organophosphate pesticide (OP) that has significant potential for accidental and intentional poisoning of wildlife, domestic animals and humans. The aim of the study is to investigate the correlation between cholinesterase activity and oxidative stress parameters in liver and diaphragm by continuous monitoring as a function of time during prolonged use of diazinon. Wistar rats were treated orally with diazinon (55 mg/kg/day): 7, 14, 21 and 28 days. At the end of each period, blood, liver and diaphragm were collected to examine cholinesterase activity and enzymatic/non-enzymatic oxidative stress parameters: superoxide dismutase 1 (SOD1), catalase (CAT), thiobarbituric acid substances (TBARS), protein carbonyl groups. In all four time periods, there was a significant change in acetylcholinesterase (AChE) in erythrocytes and butyrylcholinesterase (BuChE) in blood plasma, CAT in liver and diaphragm and SOD1 in diaphragm. Parameters significantly altered during the cholinergic crisis included: cholinesterases and TBARS in liver and diaphragm and partially SOD1 in liver. Protein carbonyl groups in liver and diaphragm were significantly altered outside the cholinergic crisis. In the liver, there was a very strong negative correlation between BuChE and TBARS in all four time periods and BuChE and CAT on day 7. In the diaphragm, a very strong negative correlation was found between AChE and TBARS at days 7 and 14, and a very strong positive correlation between AChE and SOD1 at days 14, 21 and 28. A better understanding of the relationship between cholinergic overstimulation and oxidative stress may help to better assess health status in prolonged OPs intoxication.",
publisher = "Elsevier",
journal = "Toxicology and Applied Pharmacology",
title = "The relationship between the cholinergic mechanism of toxicity and oxidative stress in rats during subacute diazinon poisoning",
pages = "116598",
volume = "473",
doi = "10.1016/j.taap.2023.116598"
}

Ivanović, S. R., Borozan, N., Ćupić Miladinović, D., Živković, I.,& Borozan, S.. (2023). The relationship between the cholinergic mechanism of toxicity and oxidative stress in rats during subacute diazinon poisoning. in Toxicology and Applied Pharmacology
Elsevier., 473, 116598.
https://doi.org/10.1016/j.taap.2023.116598

Ivanović SR, Borozan N, Ćupić Miladinović D, Živković I, Borozan S. The relationship between the cholinergic mechanism of toxicity and oxidative stress in rats during subacute diazinon poisoning. in Toxicology and Applied Pharmacology. 2023;473:116598.
doi:10.1016/j.taap.2023.116598 .

Ivanović, Saša R., Borozan, Nevena, Ćupić Miladinović, Dejana, Živković, Irena, Borozan, Sunčica, "The relationship between the cholinergic mechanism of toxicity and oxidative stress in rats during subacute diazinon poisoning" in Toxicology and Applied Pharmacology, 473 (2023):116598,
https://doi.org/10.1016/j.taap.2023.116598 . .

TY  - JOUR
AU  - Dragačević, Luka
AU  - Lopandić, Zorana
AU  - Gavrović-Jankulović, Marija
AU  - Živković, Irena
AU  - Blagojević, Veljko
AU  - Polović, Natalija
AU  - Minić, Rajna
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/621
AB  - The surface of microorganisms is covered with carbohydrates, which makes them unique, self-sustaining glycan probes. Lectins are able to bind to these probes, and this interaction can be exploited for selecting microorganisms or novel lectins. To examine lectin-microorganism interactions, we have previously developed an enzyme-linked lectin sorbent assay (ELLSA) with whole bacterial cells. To further test the validity of this methodology, here we compare it with flow cytometry. For this purpose, we used biotinylated recombinantly produced lectin from Musa acuminata (BanLec), this lectin’s recombinantly produced chimera with green fluorescent protein (BanLec-eGFP) and a lectin from Ricinus communis (RCA120), both biotinylated and FITC labeled. Parallel testing showed equivalent results for the two methods, in terms of the presence or absence of binding, with signal intensity yielding high Pearson correlation coefficient of 0.8 for BanLec and 0.95 for RCA120. The ELLSA method demonstrated multiple advantages, such as reliability and convenience for high-throughput analysis; it also required less lectin and yielded more consistent results. As such, ELLSA proved to be a useful tool for profiling microbial glycan structures or testing novel lectins.
PB  - Springer
T2  - Applied Biochemistry and Biotechnology
T1  - Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans
EP  - 2060
SP  - 2047
VL  - 194
DO  - 10.1007/s12010-021-03772-w
ER  - 

@article{
author = "Dragačević, Luka and Lopandić, Zorana and Gavrović-Jankulović, Marija and Živković, Irena and Blagojević, Veljko and Polović, Natalija and Minić, Rajna",
year = "2022",
abstract = "The surface of microorganisms is covered with carbohydrates, which makes them unique, self-sustaining glycan probes. Lectins are able to bind to these probes, and this interaction can be exploited for selecting microorganisms or novel lectins. To examine lectin-microorganism interactions, we have previously developed an enzyme-linked lectin sorbent assay (ELLSA) with whole bacterial cells. To further test the validity of this methodology, here we compare it with flow cytometry. For this purpose, we used biotinylated recombinantly produced lectin from Musa acuminata (BanLec), this lectin’s recombinantly produced chimera with green fluorescent protein (BanLec-eGFP) and a lectin from Ricinus communis (RCA120), both biotinylated and FITC labeled. Parallel testing showed equivalent results for the two methods, in terms of the presence or absence of binding, with signal intensity yielding high Pearson correlation coefficient of 0.8 for BanLec and 0.95 for RCA120. The ELLSA method demonstrated multiple advantages, such as reliability and convenience for high-throughput analysis; it also required less lectin and yielded more consistent results. As such, ELLSA proved to be a useful tool for profiling microbial glycan structures or testing novel lectins.",
publisher = "Springer",
journal = "Applied Biochemistry and Biotechnology",
title = "Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans",
pages = "2060-2047",
volume = "194",
doi = "10.1007/s12010-021-03772-w"
}

Dragačević, L., Lopandić, Z., Gavrović-Jankulović, M., Živković, I., Blagojević, V., Polović, N.,& Minić, R.. (2022). Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans. in Applied Biochemistry and Biotechnology
Springer., 194, 2047-2060.
https://doi.org/10.1007/s12010-021-03772-w

Dragačević L, Lopandić Z, Gavrović-Jankulović M, Živković I, Blagojević V, Polović N, Minić R. Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans. in Applied Biochemistry and Biotechnology. 2022;194:2047-2060.
doi:10.1007/s12010-021-03772-w .

Dragačević, Luka, Lopandić, Zorana, Gavrović-Jankulović, Marija, Živković, Irena, Blagojević, Veljko, Polović, Natalija, Minić, Rajna, "Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans" in Applied Biochemistry and Biotechnology, 194 (2022):2047-2060,
https://doi.org/10.1007/s12010-021-03772-w . .

TY  - DATA
AU  - Dragačević, Luka
AU  - Lopandić, Zorana
AU  - Gavrović-Jankulović, Marija
AU  - Živković, Irena
AU  - Blagojević, Veljko
AU  - Polović, Natalija
AU  - Minić, Rajna
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/642
AB  - SDS-PAGE showing: Lane 1 – purified banana lectin – BanLec; Lane 2 – chimera of banana lectin and enhanced green fluorescent protein BanLec-eGFP; Lane 3 – MW – molecular weight markers; Table 1. Repeatability of flow cytometric detection of different quantities of BL-eGFP binding to C. albicans; Table 2. Repeatability of ELLSA detection of different quantities of BanLec-B binding to C. albicans; Table 3. Repeatability of flow cytometric detection of different quantities of RCA120-FITC binding to L. casei DG; Table 4. Repeatability of ELLSA detection of different quantities of RCA120-B binding to L. casei DG; Table 5. Reproducibility of BanLec-B binding to 21 different microorganisms. Experiments were done in three different laboratories, with preparing new plates each time; Fig. 1 Determining linearity of ELLSA method, by measuring binding between C.albicans and different quantity of BanLec-B; Fig. 2 Determining linearity of flow cytometry, by measuring binding between C.albicans and different quantity of BanLec-eGFP; Fig. 3 Determining linearity of ELLSA method, by measuring binding between L.casei DG and different quantity of RCA120; Fig. 4 Determining linearity of flow cytometry, by measuring binding between L.casei DG and different quantity of RCA120.
PB  - Springer
T2  - Applied Biochemistry and Biotechnology
T1  - Supplementary information for the article: Dragačević, L.; Lopandić, Z.; Gavrović-Jankulović, M.; Živković, I.; Blagojević, V.; Polović, N.; Minić, R. Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans. Applied Biochemistry and Biotechnology 2022, 194, 2047–2060. https://doi.org/10.1007/s12010-021-03772-w.
EP  - 2060
SP  - 2047
VL  - 194
UR  - https://hdl.handle.net/21.15107/rcub_intor_642
ER  - 

@misc{
author = "Dragačević, Luka and Lopandić, Zorana and Gavrović-Jankulović, Marija and Živković, Irena and Blagojević, Veljko and Polović, Natalija and Minić, Rajna",
year = "2022",
abstract = "SDS-PAGE showing: Lane 1 – purified banana lectin – BanLec; Lane 2 – chimera of banana lectin and enhanced green fluorescent protein BanLec-eGFP; Lane 3 – MW – molecular weight markers; Table 1. Repeatability of flow cytometric detection of different quantities of BL-eGFP binding to C. albicans; Table 2. Repeatability of ELLSA detection of different quantities of BanLec-B binding to C. albicans; Table 3. Repeatability of flow cytometric detection of different quantities of RCA120-FITC binding to L. casei DG; Table 4. Repeatability of ELLSA detection of different quantities of RCA120-B binding to L. casei DG; Table 5. Reproducibility of BanLec-B binding to 21 different microorganisms. Experiments were done in three different laboratories, with preparing new plates each time; Fig. 1 Determining linearity of ELLSA method, by measuring binding between C.albicans and different quantity of BanLec-B; Fig. 2 Determining linearity of flow cytometry, by measuring binding between C.albicans and different quantity of BanLec-eGFP; Fig. 3 Determining linearity of ELLSA method, by measuring binding between L.casei DG and different quantity of RCA120; Fig. 4 Determining linearity of flow cytometry, by measuring binding between L.casei DG and different quantity of RCA120.",
publisher = "Springer",
journal = "Applied Biochemistry and Biotechnology",
title = "Supplementary information for the article: Dragačević, L.; Lopandić, Z.; Gavrović-Jankulović, M.; Živković, I.; Blagojević, V.; Polović, N.; Minić, R. Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans. Applied Biochemistry and Biotechnology 2022, 194, 2047–2060. https://doi.org/10.1007/s12010-021-03772-w.",
pages = "2060-2047",
volume = "194",
url = "https://hdl.handle.net/21.15107/rcub_intor_642"
}

Dragačević, L., Lopandić, Z., Gavrović-Jankulović, M., Živković, I., Blagojević, V., Polović, N.,& Minić, R.. (2022). Supplementary information for the article: Dragačević, L.; Lopandić, Z.; Gavrović-Jankulović, M.; Živković, I.; Blagojević, V.; Polović, N.; Minić, R. Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans. Applied Biochemistry and Biotechnology 2022, 194, 2047–2060. https://doi.org/10.1007/s12010-021-03772-w.. in Applied Biochemistry and Biotechnology
Springer., 194, 2047-2060.
https://hdl.handle.net/21.15107/rcub_intor_642

Dragačević L, Lopandić Z, Gavrović-Jankulović M, Živković I, Blagojević V, Polović N, Minić R. Supplementary information for the article: Dragačević, L.; Lopandić, Z.; Gavrović-Jankulović, M.; Živković, I.; Blagojević, V.; Polović, N.; Minić, R. Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans. Applied Biochemistry and Biotechnology 2022, 194, 2047–2060. https://doi.org/10.1007/s12010-021-03772-w.. in Applied Biochemistry and Biotechnology. 2022;194:2047-2060.
https://hdl.handle.net/21.15107/rcub_intor_642 .

Dragačević, Luka, Lopandić, Zorana, Gavrović-Jankulović, Marija, Živković, Irena, Blagojević, Veljko, Polović, Natalija, Minić, Rajna, "Supplementary information for the article: Dragačević, L.; Lopandić, Z.; Gavrović-Jankulović, M.; Živković, I.; Blagojević, V.; Polović, N.; Minić, R. Comparison of Enzyme-Linked Lectin Sorbent Assay and Flow Cytometry for Profiling Microbial Glycans. Applied Biochemistry and Biotechnology 2022, 194, 2047–2060. https://doi.org/10.1007/s12010-021-03772-w." in Applied Biochemistry and Biotechnology, 194 (2022):2047-2060,
https://hdl.handle.net/21.15107/rcub_intor_642 .

TY  - JOUR
AU  - Knežević, Sanja
AU  - Kosanović, Dejana
AU  - Dragačević, Luka
AU  - Živković, Irena
AU  - Ilić, Vesna
AU  - Hajduković, Ljiljana
AU  - Savić, Olivera
AU  - Minić, Rajna
PY  - 2022
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1255
UR  - http://intor.torlakinstitut.com/handle/123456789/650
AB  - S. pneumoniae is an important human pathogen which has a polysaccharide capsule with virulent properties. This work aims to estimate the titres of S. pneumoniae specific IgG and IgA isotypes, with respect to age and sex. An in-house whole bacterial cell ELISA was used for the determination of relative levels and endpoint titres of IgG subclasses and IgA1 subclass specific for S. pneumoniae serogroup 1, and to quantify specific IgG1 and IgG2 levels. Significantly lower anti-pneumococcus IgG1 titres were found in older individuals, which was more pronounced in men. Lower IgG2 titres were detected in men over 50 years of age, in comparison to women under 50 years of age. The levels of IgG3 and IgG4 did not differ between different sex and age groups. Lower IgA1 levels were detected in male individuals in both age groups in comparison to females under 50 years of age. The levels of IgG1 showed a moderate correlation with IgG4 in younger individuals of both sexes (r = 0.61 in men and 0.63 in women) which was not noted in the older age group. We highlight the deficiency in humoral immunity in older people, especially male and suggest immunization of this population with pneumococcal vaccines.
PB  - Elsevier
T2  - Comparative Immunology, Microbiology and Infectious Diseases
T1  - Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1
SP  - 101834
VL  - 87
DO  - 10.1016/j.cimid.2022.101834
ER  - 

@article{
author = "Knežević, Sanja and Kosanović, Dejana and Dragačević, Luka and Živković, Irena and Ilić, Vesna and Hajduković, Ljiljana and Savić, Olivera and Minić, Rajna",
year = "2022",
abstract = "S. pneumoniae is an important human pathogen which has a polysaccharide capsule with virulent properties. This work aims to estimate the titres of S. pneumoniae specific IgG and IgA isotypes, with respect to age and sex. An in-house whole bacterial cell ELISA was used for the determination of relative levels and endpoint titres of IgG subclasses and IgA1 subclass specific for S. pneumoniae serogroup 1, and to quantify specific IgG1 and IgG2 levels. Significantly lower anti-pneumococcus IgG1 titres were found in older individuals, which was more pronounced in men. Lower IgG2 titres were detected in men over 50 years of age, in comparison to women under 50 years of age. The levels of IgG3 and IgG4 did not differ between different sex and age groups. Lower IgA1 levels were detected in male individuals in both age groups in comparison to females under 50 years of age. The levels of IgG1 showed a moderate correlation with IgG4 in younger individuals of both sexes (r = 0.61 in men and 0.63 in women) which was not noted in the older age group. We highlight the deficiency in humoral immunity in older people, especially male and suggest immunization of this population with pneumococcal vaccines.",
publisher = "Elsevier",
journal = "Comparative Immunology, Microbiology and Infectious Diseases",
title = "Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1",
pages = "101834",
volume = "87",
doi = "10.1016/j.cimid.2022.101834"
}

Knežević, S., Kosanović, D., Dragačević, L., Živković, I., Ilić, V., Hajduković, L., Savić, O.,& Minić, R.. (2022). Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1. in Comparative Immunology, Microbiology and Infectious Diseases
Elsevier., 87, 101834.
https://doi.org/10.1016/j.cimid.2022.101834

Knežević S, Kosanović D, Dragačević L, Živković I, Ilić V, Hajduković L, Savić O, Minić R. Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1. in Comparative Immunology, Microbiology and Infectious Diseases. 2022;87:101834.
doi:10.1016/j.cimid.2022.101834 .

Knežević, Sanja, Kosanović, Dejana, Dragačević, Luka, Živković, Irena, Ilić, Vesna, Hajduković, Ljiljana, Savić, Olivera, Minić, Rajna, "Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1" in Comparative Immunology, Microbiology and Infectious Diseases, 87 (2022):101834,
https://doi.org/10.1016/j.cimid.2022.101834 . .

TY  - JOUR
AU  - Knežević, Sanja
AU  - Kosanović, Dejana
AU  - Dragačević, Luka
AU  - Živković, Irena
AU  - Ilić, Vesna
AU  - Hajduković, Ljiljana
AU  - Savić, Olivera
AU  - Minić, Rajna
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/651
AB  - S. pneumoniae is an important human pathogen which has a polysaccharide capsule with virulent properties. This work aims to estimate the titres of S. pneumoniae specific IgG and IgA isotypes, with respect to age and sex. An in-house whole bacterial cell ELISA was used for the determination of relative levels and endpoint titres of IgG subclasses and IgA1 subclass specific for S. pneumoniae serogroup 1, and to quantify specific IgG1 and IgG2 levels. Significantly lower anti-pneumococcus IgG1 titres were found in older individuals, which was more pronounced in men. Lower IgG2 titres were detected in men over 50 years of age, in comparison to women under 50 years of age. The levels of IgG3 and IgG4 did not differ between different sex and age groups. Lower IgA1 levels were detected in male individuals in both age groups in comparison to females under 50 years of age. The levels of IgG1 showed a moderate correlation with IgG4 in younger individuals of both sexes (r = 0.61 in men and 0.63 in women) which was not noted in the older age group. We highlight the deficiency in humoral immunity in older people, especially male and suggest immunization of this population with pneumococcal vaccines.
PB  - Elsevier
T2  - Comparative Immunology, Microbiology and Infectious Diseases
T1  - Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1
SP  - 101834
VL  - 87
DO  - 10.1016/j.cimid.2022.101834
ER  - 

@article{
author = "Knežević, Sanja and Kosanović, Dejana and Dragačević, Luka and Živković, Irena and Ilić, Vesna and Hajduković, Ljiljana and Savić, Olivera and Minić, Rajna",
year = "2022",
abstract = "S. pneumoniae is an important human pathogen which has a polysaccharide capsule with virulent properties. This work aims to estimate the titres of S. pneumoniae specific IgG and IgA isotypes, with respect to age and sex. An in-house whole bacterial cell ELISA was used for the determination of relative levels and endpoint titres of IgG subclasses and IgA1 subclass specific for S. pneumoniae serogroup 1, and to quantify specific IgG1 and IgG2 levels. Significantly lower anti-pneumococcus IgG1 titres were found in older individuals, which was more pronounced in men. Lower IgG2 titres were detected in men over 50 years of age, in comparison to women under 50 years of age. The levels of IgG3 and IgG4 did not differ between different sex and age groups. Lower IgA1 levels were detected in male individuals in both age groups in comparison to females under 50 years of age. The levels of IgG1 showed a moderate correlation with IgG4 in younger individuals of both sexes (r = 0.61 in men and 0.63 in women) which was not noted in the older age group. We highlight the deficiency in humoral immunity in older people, especially male and suggest immunization of this population with pneumococcal vaccines.",
publisher = "Elsevier",
journal = "Comparative Immunology, Microbiology and Infectious Diseases",
title = "Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1",
pages = "101834",
volume = "87",
doi = "10.1016/j.cimid.2022.101834"
}

Knežević, S., Kosanović, D., Dragačević, L., Živković, I., Ilić, V., Hajduković, L., Savić, O.,& Minić, R.. (2022). Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1. in Comparative Immunology, Microbiology and Infectious Diseases
Elsevier., 87, 101834.
https://doi.org/10.1016/j.cimid.2022.101834

Knežević S, Kosanović D, Dragačević L, Živković I, Ilić V, Hajduković L, Savić O, Minić R. Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1. in Comparative Immunology, Microbiology and Infectious Diseases. 2022;87:101834.
doi:10.1016/j.cimid.2022.101834 .

Knežević, Sanja, Kosanović, Dejana, Dragačević, Luka, Živković, Irena, Ilić, Vesna, Hajduković, Ljiljana, Savić, Olivera, Minić, Rajna, "Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1" in Comparative Immunology, Microbiology and Infectious Diseases, 87 (2022):101834,
https://doi.org/10.1016/j.cimid.2022.101834 . .

TY  - JOUR
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Živković, Irena
AU  - Petrović, Raisa
AU  - Leposavić, Gordana
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/620
AB  - Aims: Given that deprivation of noradrenaline acting on lymphocytes through β-adrenoceptor influences antibody response, the effects of propranolol treatment beginning two days before immunization with quadrivalent inactivated influenza vaccine (QIV) on IgG response and underlying cellular molecular mechanism in mice were investigated.

Main methods: Twenty-one days post-immunization the total QIV antigen-specific IgG titer and IgG subclass titers in sera were determined using ELISA. Additionally, the total counts of germinal centre (GC) B cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in draining lymph nodes (dLNs) and spleens, in vitro proliferation of interacting B cells and Th cells and IL-21 synthesis in Th cells in response to QIV antigens and/or mitogen were attested using flow cytometry analysis. In QIV antigen-stimulated dLN cell and splenocyte cultures were also measured concentrations of INF-γ and IL-4, cytokines upregulating IgG2a and IgG1 synthesis, respectively.

Key findings: Propranolol decreased the total QIV antigen-specific IgG titer. This correlated with lower GC B cell count and the shift in Tfr/Tfh cell and Tfr/GC B cell ratio towards Tfr in propranolol-treated mice compared with controls. Consistently, QIV antigen-stimulated proliferation of B cells and Th cells from propranolol-treated mice in vitro was impaired. This correlated with the lower frequency of QIV antigen-specific IL-21-producing cells among Th cells. Additionally, in propranolol-treated mice, in accordance with the changes in INF-γ/IL-4 ratio in dLN cell/splenocyte cultures, serum IgG2a/IgG1 ratio was shifted towards IgG1 reflecting decreased IgG2a response.

Significance: The study indicates that chronic propranolol treatment may impair response to QIV.
PB  - Elsevier
T2  - Life Sciences
T1  - B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor
SP  - 120617
VL  - 301
DO  - 10.1016/j.lfs.2022.120617
ER  - 

@article{
author = "Bufan, Biljana and Arsenović-Ranin, Nevena and Živković, Irena and Petrović, Raisa and Leposavić, Gordana",
year = "2022",
abstract = "Aims: Given that deprivation of noradrenaline acting on lymphocytes through β-adrenoceptor influences antibody response, the effects of propranolol treatment beginning two days before immunization with quadrivalent inactivated influenza vaccine (QIV) on IgG response and underlying cellular molecular mechanism in mice were investigated.

Main methods: Twenty-one days post-immunization the total QIV antigen-specific IgG titer and IgG subclass titers in sera were determined using ELISA. Additionally, the total counts of germinal centre (GC) B cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in draining lymph nodes (dLNs) and spleens, in vitro proliferation of interacting B cells and Th cells and IL-21 synthesis in Th cells in response to QIV antigens and/or mitogen were attested using flow cytometry analysis. In QIV antigen-stimulated dLN cell and splenocyte cultures were also measured concentrations of INF-γ and IL-4, cytokines upregulating IgG2a and IgG1 synthesis, respectively.

Key findings: Propranolol decreased the total QIV antigen-specific IgG titer. This correlated with lower GC B cell count and the shift in Tfr/Tfh cell and Tfr/GC B cell ratio towards Tfr in propranolol-treated mice compared with controls. Consistently, QIV antigen-stimulated proliferation of B cells and Th cells from propranolol-treated mice in vitro was impaired. This correlated with the lower frequency of QIV antigen-specific IL-21-producing cells among Th cells. Additionally, in propranolol-treated mice, in accordance with the changes in INF-γ/IL-4 ratio in dLN cell/splenocyte cultures, serum IgG2a/IgG1 ratio was shifted towards IgG1 reflecting decreased IgG2a response.

Significance: The study indicates that chronic propranolol treatment may impair response to QIV.",
publisher = "Elsevier",
journal = "Life Sciences",
title = "B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor",
pages = "120617",
volume = "301",
doi = "10.1016/j.lfs.2022.120617"
}

Bufan, B., Arsenović-Ranin, N., Živković, I., Petrović, R.,& Leposavić, G.. (2022). B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor. in Life Sciences
Elsevier., 301, 120617.
https://doi.org/10.1016/j.lfs.2022.120617

Bufan B, Arsenović-Ranin N, Živković I, Petrović R, Leposavić G. B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor. in Life Sciences. 2022;301:120617.
doi:10.1016/j.lfs.2022.120617 .

Bufan, Biljana, Arsenović-Ranin, Nevena, Živković, Irena, Petrović, Raisa, Leposavić, Gordana, "B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor" in Life Sciences, 301 (2022):120617,
https://doi.org/10.1016/j.lfs.2022.120617 . .

TY  - JOUR
AU  - Milovanović, Vladimir
AU  - Minić, Rajna
AU  - Vakić, J.
AU  - Ivanović, S.
AU  - Cupić, V.
AU  - Borozan, S.
AU  - Nešić, A.
AU  - Živković, Irena
PY  - 2021
UR  - http://intor.torlakinstitut.com/handle/123456789/572
AB  - The MTT assay is routinely used to detect the activity of living cells. While working with Vipera ammodytes venom we detected the reduction of MTT without the presence of cells, in a concentration-dependent manner. By combining non-reducing PAGE, L-amino acid oxidase (LAAO) assays, and standard MTT assays, we established and confirmed that venom MTT reduction is catalyzed by only one enzyme, the LAAO. Even though it was previously known that the dimeric and tetrameric forms of LAAO are active, we conclude that the enzyme is also active in the monomeric form. Our results have led to the definition of a new MTT assay in a microtiter plate for in vitro testing of svLAAO activity i.e. from the venom of the V. ammodytes snake. Potentially, this method can be used for testing hemorrhagic venoms of other snakes as well as the LAAO neutralization capability of appropriate antivenoms.
PB  - Elsevier Ltd
T2  - Toxicon
T1  - MTT based L-aminoacid oxidase activity test for determination of antivenom potency against Vipera ammodytes envenomation
EP  - 65
SP  - 57
VL  - 192
DO  - 10.1016/j.toxicon.2021.01.012
ER  - 

@article{
author = "Milovanović, Vladimir and Minić, Rajna and Vakić, J. and Ivanović, S. and Cupić, V. and Borozan, S. and Nešić, A. and Živković, Irena",
year = "2021",
abstract = "The MTT assay is routinely used to detect the activity of living cells. While working with Vipera ammodytes venom we detected the reduction of MTT without the presence of cells, in a concentration-dependent manner. By combining non-reducing PAGE, L-amino acid oxidase (LAAO) assays, and standard MTT assays, we established and confirmed that venom MTT reduction is catalyzed by only one enzyme, the LAAO. Even though it was previously known that the dimeric and tetrameric forms of LAAO are active, we conclude that the enzyme is also active in the monomeric form. Our results have led to the definition of a new MTT assay in a microtiter plate for in vitro testing of svLAAO activity i.e. from the venom of the V. ammodytes snake. Potentially, this method can be used for testing hemorrhagic venoms of other snakes as well as the LAAO neutralization capability of appropriate antivenoms.",
publisher = "Elsevier Ltd",
journal = "Toxicon",
title = "MTT based L-aminoacid oxidase activity test for determination of antivenom potency against Vipera ammodytes envenomation",
pages = "65-57",
volume = "192",
doi = "10.1016/j.toxicon.2021.01.012"
}

Milovanović, V., Minić, R., Vakić, J., Ivanović, S., Cupić, V., Borozan, S., Nešić, A.,& Živković, I.. (2021). MTT based L-aminoacid oxidase activity test for determination of antivenom potency against Vipera ammodytes envenomation. in Toxicon
Elsevier Ltd., 192, 57-65.
https://doi.org/10.1016/j.toxicon.2021.01.012

Milovanović V, Minić R, Vakić J, Ivanović S, Cupić V, Borozan S, Nešić A, Živković I. MTT based L-aminoacid oxidase activity test for determination of antivenom potency against Vipera ammodytes envenomation. in Toxicon. 2021;192:57-65.
doi:10.1016/j.toxicon.2021.01.012 .

Milovanović, Vladimir, Minić, Rajna, Vakić, J., Ivanović, S., Cupić, V., Borozan, S., Nešić, A., Živković, Irena, "MTT based L-aminoacid oxidase activity test for determination of antivenom potency against Vipera ammodytes envenomation" in Toxicon, 192 (2021):57-65,
https://doi.org/10.1016/j.toxicon.2021.01.012 . .

TY  - JOUR
AU  - Mihaljević, Olgica
AU  - Živančević-Simonović, Snežana
AU  - Lučić-Tomić, Aleksandra
AU  - Živković, Irena
AU  - Minić, Rajna
AU  - Mijatović-Teodorović, Ljiljana
AU  - Jovanović, Zorica
AU  - Anđelković, Marija
AU  - Stanojević-Pirković, Marijana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/558
AB  - Background: The aim of this study was to compare serum sclerostin concentrations in patients with thyroid dysfunction with euthyroid control subjects and to assess the relationship between sclerostin and markers of bone metabolism (osteocalcin and beta-cross-laps). Methods: The study included 30 patients with thyroid dysfunction (hypothyroidism, hyperthyroidism and subclinical hyperthyroidism) and ten euthyroid controls. Free thyroxine (FT4) was measured by radioimmunoassay, while thyroid stimulating hormone (TSH) concentration was determined immunoradiometrically. We used an ELISA kit to determine the sclerostin level. The electrochemiluminescence method was applied for measuring the bone markers. Results: Sclerostin levels were significantly lower in hypothyroid patients (p=0.009) and significantly elevated in hyperthyroid patients (p=0.008) compared to control values. Hyperthyroid patients also had higher sclerostin than patients with subclinical hyperthyroidism (p=0.013). Sclerostin concentrations were negatively correlated with TSH levels (r=-0.746, p lt 0.001), but positively with FT4 (r=0.696, p  lt  0.001). Moreover, sclerostin was positively associated with osteocalcin (r=0.605, p=0.005) and beta-cross-laps levels (r=0.573, p=0.008) in all thyroid patients. Conclusions: Serum sclerostin is significantly affected in subjects with thyroid dysfunction. Both sclerostin and thyroid status affect bone homeostasis, which is reflected through the significant correlations with osteocalcin and beta-cross-laps.
AB  - Uvod: Cilj ove studije bio je da uporedimo serumske koncentracije sklerostina kod pacijenata sa disfunkcijom štitaste žlezde u odnosu na eutiroidne kontrolne ispitanike, i da procenimo odnos između sklerostina i markera koštanog metabolizma (osteokalcina i beta-cross-lapsa) u istoj populaciji. Metode: Studijom je obuhvaćeno 30 pacijenata sa disfunkcijom štitaste žlezde (hipotireozom, hipertireozom i supkliničkom hipertireozom) i 10 eutiroidnih kontrola. Slobodni tiroksin (FT4) meren je radioimunološkom metodom, dok je koncentracija tireostimulišućeg hormona (TSH) određivana imunoradiometrijski. Za merenje nivoa sklerostina koristili smo ELISA-test. Metoda elektrohemiluminiscencije primenjena je za merenje koncentracije koštanih markera. Rezultati: Nivo sklerostina bio je značajno niži kod bolesnika sa hipotireozom (p = 0,009) odnosno značajno viši kod bolesnika sa hipertireozom (p = 0,008) u poređenju sa vrednostima kod eutiroidnih kontrolnih ispitanika. Pacijenti sa hipertireozom su takođe imali statistički značajno viši nivo sklerostina u odnosu na bolesnike sa supkliničkom hipertireozom (p = 0,013). Pokazana je negativna korelacija koncentracije sklerostina i TSH (r = -0,746, p  lt  0,001), odnosno pozitivna korelacija sa FT4 (r = 0,696, p  lt  0,001) kod pacijenata sa tireoidnom disfunkcijom. Štaviše, sklerostin pozitivno korelira sa koncentracijom osteokalcina (r = 0,605, p = 0,005) i beta-cross-lapsa (r = 0,573, p = 0,008) kod ovih pacijenata. Zaključak: Serumski nivoi sklerostina izmenjeni su kod osoba sa disfunkcijom štitaste žlezde. Sklerostin zajedno sa tireoidnim statusom utiče na koštani metabolizam, što se ogleda u njegovoj značajnoj korelaciji sa osteokalcinom i beta-cross-lapsom.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - The association of circulating sclerostin level with markers of bone metabolism in patients with thyroid dysfunction
T1  - Veza cirkulišućeg nivoa sklerostina sa markerima metabolizma kostiju kod pacijenata sa poremećajem rada štitaste žlezde
EP  - 443
IS  - 4
SP  - 436
VL  - 39
DO  - 10.5937/jomb0-24943
ER  - 

@article{
author = "Mihaljević, Olgica and Živančević-Simonović, Snežana and Lučić-Tomić, Aleksandra and Živković, Irena and Minić, Rajna and Mijatović-Teodorović, Ljiljana and Jovanović, Zorica and Anđelković, Marija and Stanojević-Pirković, Marijana",
year = "2020",
abstract = "Background: The aim of this study was to compare serum sclerostin concentrations in patients with thyroid dysfunction with euthyroid control subjects and to assess the relationship between sclerostin and markers of bone metabolism (osteocalcin and beta-cross-laps). Methods: The study included 30 patients with thyroid dysfunction (hypothyroidism, hyperthyroidism and subclinical hyperthyroidism) and ten euthyroid controls. Free thyroxine (FT4) was measured by radioimmunoassay, while thyroid stimulating hormone (TSH) concentration was determined immunoradiometrically. We used an ELISA kit to determine the sclerostin level. The electrochemiluminescence method was applied for measuring the bone markers. Results: Sclerostin levels were significantly lower in hypothyroid patients (p=0.009) and significantly elevated in hyperthyroid patients (p=0.008) compared to control values. Hyperthyroid patients also had higher sclerostin than patients with subclinical hyperthyroidism (p=0.013). Sclerostin concentrations were negatively correlated with TSH levels (r=-0.746, p lt 0.001), but positively with FT4 (r=0.696, p  lt  0.001). Moreover, sclerostin was positively associated with osteocalcin (r=0.605, p=0.005) and beta-cross-laps levels (r=0.573, p=0.008) in all thyroid patients. Conclusions: Serum sclerostin is significantly affected in subjects with thyroid dysfunction. Both sclerostin and thyroid status affect bone homeostasis, which is reflected through the significant correlations with osteocalcin and beta-cross-laps., Uvod: Cilj ove studije bio je da uporedimo serumske koncentracije sklerostina kod pacijenata sa disfunkcijom štitaste žlezde u odnosu na eutiroidne kontrolne ispitanike, i da procenimo odnos između sklerostina i markera koštanog metabolizma (osteokalcina i beta-cross-lapsa) u istoj populaciji. Metode: Studijom je obuhvaćeno 30 pacijenata sa disfunkcijom štitaste žlezde (hipotireozom, hipertireozom i supkliničkom hipertireozom) i 10 eutiroidnih kontrola. Slobodni tiroksin (FT4) meren je radioimunološkom metodom, dok je koncentracija tireostimulišućeg hormona (TSH) određivana imunoradiometrijski. Za merenje nivoa sklerostina koristili smo ELISA-test. Metoda elektrohemiluminiscencije primenjena je za merenje koncentracije koštanih markera. Rezultati: Nivo sklerostina bio je značajno niži kod bolesnika sa hipotireozom (p = 0,009) odnosno značajno viši kod bolesnika sa hipertireozom (p = 0,008) u poređenju sa vrednostima kod eutiroidnih kontrolnih ispitanika. Pacijenti sa hipertireozom su takođe imali statistički značajno viši nivo sklerostina u odnosu na bolesnike sa supkliničkom hipertireozom (p = 0,013). Pokazana je negativna korelacija koncentracije sklerostina i TSH (r = -0,746, p  lt  0,001), odnosno pozitivna korelacija sa FT4 (r = 0,696, p  lt  0,001) kod pacijenata sa tireoidnom disfunkcijom. Štaviše, sklerostin pozitivno korelira sa koncentracijom osteokalcina (r = 0,605, p = 0,005) i beta-cross-lapsa (r = 0,573, p = 0,008) kod ovih pacijenata. Zaključak: Serumski nivoi sklerostina izmenjeni su kod osoba sa disfunkcijom štitaste žlezde. Sklerostin zajedno sa tireoidnim statusom utiče na koštani metabolizam, što se ogleda u njegovoj značajnoj korelaciji sa osteokalcinom i beta-cross-lapsom.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "The association of circulating sclerostin level with markers of bone metabolism in patients with thyroid dysfunction, Veza cirkulišućeg nivoa sklerostina sa markerima metabolizma kostiju kod pacijenata sa poremećajem rada štitaste žlezde",
pages = "443-436",
number = "4",
volume = "39",
doi = "10.5937/jomb0-24943"
}

Mihaljević, O., Živančević-Simonović, S., Lučić-Tomić, A., Živković, I., Minić, R., Mijatović-Teodorović, L., Jovanović, Z., Anđelković, M.,& Stanojević-Pirković, M.. (2020). The association of circulating sclerostin level with markers of bone metabolism in patients with thyroid dysfunction. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 39(4), 436-443.
https://doi.org/10.5937/jomb0-24943

Mihaljević O, Živančević-Simonović S, Lučić-Tomić A, Živković I, Minić R, Mijatović-Teodorović L, Jovanović Z, Anđelković M, Stanojević-Pirković M. The association of circulating sclerostin level with markers of bone metabolism in patients with thyroid dysfunction. in Journal of Medical Biochemistry. 2020;39(4):436-443.
doi:10.5937/jomb0-24943 .

Mihaljević, Olgica, Živančević-Simonović, Snežana, Lučić-Tomić, Aleksandra, Živković, Irena, Minić, Rajna, Mijatović-Teodorović, Ljiljana, Jovanović, Zorica, Anđelković, Marija, Stanojević-Pirković, Marijana, "The association of circulating sclerostin level with markers of bone metabolism in patients with thyroid dysfunction" in Journal of Medical Biochemistry, 39, no. 4 (2020):436-443,
https://doi.org/10.5937/jomb0-24943 . .

TY  - CHAP
AU  - Živković, Irena
AU  - Minić, Rajna
AU  - Dimitrijević, Ljiljana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/549
AB  - Immunoglobulins, either natural or induced, represent powerful means for eliminating microbial threats. For decades, vaccines have been used which function by inducing antibodies for the successful elimination of microbes, preventing disease and mortality. Polyclonal immunoglobulin products from human plasma were used for the first time to treat immune deficiency during the 1950s. Nowadays, the administration of immunoglobulin, either intravenous or subcutaneous, is the cornerstone of the treatment of primary immunodeficiency affecting the humoral immune system. The therapy can help people with weakened or underdeveloped immune system fight off infections. This is also the treatment of choice for certain autoimmune and neurological diseases. The polyclonal antibody preparation consists of both natural antibodies and antigen-induced antibodies and reflects the history of antigen experience of the donor population. Natural antibodies are germline-encoded, polyspecific, low-affinity antibodies that also have a regulatory role in maintaining the immune system homeostasis. Antibody preparations, enriched for certain desired specificities, or hyperimmune human globulins are used for prophylaxis and treatment of infectious diseases with a high mortality rate. It was shown that lymphocytes from survivors of viral infections, without available vaccines, could be used for protective monoclonal antibodies production. This chapter provides insight into the current knowledge of the usage of antibody preparations, efficacy and mechanism of action, with respect to specific diseases, including the treatment of infectious diseases and future prospects.
PB  - Bentham Science Publishers
T2  - Frontiers in Clinical Drug Research - Anti Infectives
T1  - Antimicrobial immunoglobulin prophylaxis and therapy
EP  - 205
IS  - 1
SP  - 165
VL  - 6
DO  - 10.2174/9789811425745120060007
ER  - 

@inbook{
author = "Živković, Irena and Minić, Rajna and Dimitrijević, Ljiljana",
year = "2020",
abstract = "Immunoglobulins, either natural or induced, represent powerful means for eliminating microbial threats. For decades, vaccines have been used which function by inducing antibodies for the successful elimination of microbes, preventing disease and mortality. Polyclonal immunoglobulin products from human plasma were used for the first time to treat immune deficiency during the 1950s. Nowadays, the administration of immunoglobulin, either intravenous or subcutaneous, is the cornerstone of the treatment of primary immunodeficiency affecting the humoral immune system. The therapy can help people with weakened or underdeveloped immune system fight off infections. This is also the treatment of choice for certain autoimmune and neurological diseases. The polyclonal antibody preparation consists of both natural antibodies and antigen-induced antibodies and reflects the history of antigen experience of the donor population. Natural antibodies are germline-encoded, polyspecific, low-affinity antibodies that also have a regulatory role in maintaining the immune system homeostasis. Antibody preparations, enriched for certain desired specificities, or hyperimmune human globulins are used for prophylaxis and treatment of infectious diseases with a high mortality rate. It was shown that lymphocytes from survivors of viral infections, without available vaccines, could be used for protective monoclonal antibodies production. This chapter provides insight into the current knowledge of the usage of antibody preparations, efficacy and mechanism of action, with respect to specific diseases, including the treatment of infectious diseases and future prospects.",
publisher = "Bentham Science Publishers",
journal = "Frontiers in Clinical Drug Research - Anti Infectives",
booktitle = "Antimicrobial immunoglobulin prophylaxis and therapy",
pages = "205-165",
number = "1",
volume = "6",
doi = "10.2174/9789811425745120060007"
}

Živković, I., Minić, R.,& Dimitrijević, L.. (2020). Antimicrobial immunoglobulin prophylaxis and therapy. in Frontiers in Clinical Drug Research - Anti Infectives
Bentham Science Publishers., 6(1), 165-205.
https://doi.org/10.2174/9789811425745120060007

Živković I, Minić R, Dimitrijević L. Antimicrobial immunoglobulin prophylaxis and therapy. in Frontiers in Clinical Drug Research - Anti Infectives. 2020;6(1):165-205.
doi:10.2174/9789811425745120060007 .

Živković, Irena, Minić, Rajna, Dimitrijević, Ljiljana, "Antimicrobial immunoglobulin prophylaxis and therapy" in Frontiers in Clinical Drug Research - Anti Infectives, 6, no. 1 (2020):165-205,
https://doi.org/10.2174/9789811425745120060007 . .

TY  - CHAP
AU  - Živković, Irena
AU  - Minić, Rajna
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/548
AB  - The enzyme-linked immunosorbent assay (ELISA) is a commonly used analytical immunochemistry assay based on the specific bond between the antigen and the antibody. The application of this test has significantly changed the practice of medical laboratories in which it is used for detection and quantification of molecules such as hormones, peptides, antibodies, and proteins. Various technical variants of this test can detect antigen (native or foreign) or antibody, determine the intensity of the immune response whether pathological or not; the type of induced immune response as well as the innate immunity potential; and much more. These capabilities, as well as the high sensitivity and robustness of the test and a small price, make it possible to quickly and reliably diagnose diseases in most laboratories. Besides, ELISA is a test that is also used in veterinary medicine, toxicology, allergology, food industry, etc. Despite the fact that it has existed for almost 50 years, different ELISA tests with different technical solutions are still being developed, which improves and expands the application of the this exceptional test. The aim of this chapter is to empower the rider to optimize, standardize and validate an enzyme linked immunosorbent assay.
PB  - IntechOpen
T2  - ELISA Test-Perspectives and Applications
T1  - Optimization, Validation and Standardization of ELISA
DO  - 10.5772/intechopen.94338
ER  - 

@inbook{
author = "Živković, Irena and Minić, Rajna",
year = "2020",
abstract = "The enzyme-linked immunosorbent assay (ELISA) is a commonly used analytical immunochemistry assay based on the specific bond between the antigen and the antibody. The application of this test has significantly changed the practice of medical laboratories in which it is used for detection and quantification of molecules such as hormones, peptides, antibodies, and proteins. Various technical variants of this test can detect antigen (native or foreign) or antibody, determine the intensity of the immune response whether pathological or not; the type of induced immune response as well as the innate immunity potential; and much more. These capabilities, as well as the high sensitivity and robustness of the test and a small price, make it possible to quickly and reliably diagnose diseases in most laboratories. Besides, ELISA is a test that is also used in veterinary medicine, toxicology, allergology, food industry, etc. Despite the fact that it has existed for almost 50 years, different ELISA tests with different technical solutions are still being developed, which improves and expands the application of the this exceptional test. The aim of this chapter is to empower the rider to optimize, standardize and validate an enzyme linked immunosorbent assay.",
publisher = "IntechOpen",
journal = "ELISA Test-Perspectives and Applications",
booktitle = "Optimization, Validation and Standardization of ELISA",
doi = "10.5772/intechopen.94338"
}

Živković, I.,& Minić, R.. (2020). Optimization, Validation and Standardization of ELISA. in ELISA Test-Perspectives and Applications
IntechOpen..
https://doi.org/10.5772/intechopen.94338

Živković I, Minić R. Optimization, Validation and Standardization of ELISA. in ELISA Test-Perspectives and Applications. 2020;.
doi:10.5772/intechopen.94338 .

Živković, Irena, Minić, Rajna, "Optimization, Validation and Standardization of ELISA" in ELISA Test-Perspectives and Applications (2020),
https://doi.org/10.5772/intechopen.94338 . .

TY  - JOUR
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/556
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 agerelated 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 Thl/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-gamma/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  - Pergamon-Elsevier Science Ltd, Oxford
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 agerelated 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 Thl/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-gamma/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 = "Pergamon-Elsevier Science Ltd, Oxford",
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
Pergamon-Elsevier Science Ltd, Oxford., 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  - CONF
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
AU  - Živković, Irena
AU  - Prijić, Ivana
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/692
AB  - Efficacy of the immune response to vaccine depends on genetic background, sex and
age of the recipient. However, mechanisms underlying this phenomenon have not been
elucidated, yet. The study investigated influence of sex and age on serum IgG response
to seasonal trivalent inactivated split influenza vaccine (TIV) in BALB/c and C57BL/6
mice, and mechanisms underlying this response. Total serum IgG responses to
influenza virus type A strains declined with aging, in a strain-specific manner.
Consequently, strain differences (greater IgG responses in BALB/c mice) observed in
young mice (three-month-old) were abrogated in old (eighteen-month-old) ones.
However, irrespective of strain and age, females developed stronger influenza type Aspecific IgG responses than males. Despite age-related decrease in influenza B-specific
serum IgG response, it was comparable between old BALB/c and C57BL/6 mice. The
strain/sex-specific differences in age-related changes in the magnitudes of IgG
responses to TIV correlated with those in number of germinal centre (GC) B
splenocytes. These differences were related to those in B splenocyte and CD4+
splenocyte proliferation in culture upon restimulation with influenza viruses from TIV.
The magnitudes of IgG responses also correlated to T follicular regulatory (Tfr)/T
follicular helper and Tfr/GC B splenocyte ratios across all groups of mice. Aging,
irrespective of influenza virus-specificity, affected serum IgG2a(c)/IgG1 ratios
(reflecting IFN-γ/IL-4 production level ratio) in male BALB/c and female C57BL/6
mice, respectively. Thus, although in young mice of both strains these ratios were
comparable between sexes, in old females they were shifted towards IgG1 when
compared with age-matched males. Consistently, the IFN-γ/IL-4 production level ratios
in splenocyte cultures stimulated with influenza viruses from old females of both strains
were shifted towards IL-4 compared with that in age-matched male cultures. The study
stimulates further research to formulate sex-specific strategies to improve efficacy of
influenza vaccine in elderly.
PB  - Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia
C3  - Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th
T1  - Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine
UR  - https://hdl.handle.net/21.15107/rcub_intor_692
ER  - 

@conference{
author = "Petrović, Raisa and Arsenović-Ranin, Nevena and Bufan, Biljana and Živković, Irena and Prijić, Ivana and Stoiljković, Vera and Leposavić, Gordana",
year = "2019",
abstract = "Efficacy of the immune response to vaccine depends on genetic background, sex and
age of the recipient. However, mechanisms underlying this phenomenon have not been
elucidated, yet. The study investigated influence of sex and age on serum IgG response
to seasonal trivalent inactivated split influenza vaccine (TIV) in BALB/c and C57BL/6
mice, and mechanisms underlying this response. Total serum IgG responses to
influenza virus type A strains declined with aging, in a strain-specific manner.
Consequently, strain differences (greater IgG responses in BALB/c mice) observed in
young mice (three-month-old) were abrogated in old (eighteen-month-old) ones.
However, irrespective of strain and age, females developed stronger influenza type Aspecific IgG responses than males. Despite age-related decrease in influenza B-specific
serum IgG response, it was comparable between old BALB/c and C57BL/6 mice. The
strain/sex-specific differences in age-related changes in the magnitudes of IgG
responses to TIV correlated with those in number of germinal centre (GC) B
splenocytes. These differences were related to those in B splenocyte and CD4+
splenocyte proliferation in culture upon restimulation with influenza viruses from TIV.
The magnitudes of IgG responses also correlated to T follicular regulatory (Tfr)/T
follicular helper and Tfr/GC B splenocyte ratios across all groups of mice. Aging,
irrespective of influenza virus-specificity, affected serum IgG2a(c)/IgG1 ratios
(reflecting IFN-γ/IL-4 production level ratio) in male BALB/c and female C57BL/6
mice, respectively. Thus, although in young mice of both strains these ratios were
comparable between sexes, in old females they were shifted towards IgG1 when
compared with age-matched males. Consistently, the IFN-γ/IL-4 production level ratios
in splenocyte cultures stimulated with influenza viruses from old females of both strains
were shifted towards IL-4 compared with that in age-matched male cultures. The study
stimulates further research to formulate sex-specific strategies to improve efficacy of
influenza vaccine in elderly.",
publisher = "Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia",
journal = "Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th",
title = "Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine",
url = "https://hdl.handle.net/21.15107/rcub_intor_692"
}

Petrović, R., Arsenović-Ranin, N., Bufan, B., Živković, I., Prijić, I., Stoiljković, V.,& Leposavić, G.. (2019). Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine. in Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th
Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia..
https://hdl.handle.net/21.15107/rcub_intor_692

Petrović R, Arsenović-Ranin N, Bufan B, Živković I, Prijić I, Stoiljković V, Leposavić G. Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine. in Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th. 2019;.
https://hdl.handle.net/21.15107/rcub_intor_692 .

Petrović, Raisa, Arsenović-Ranin, Nevena, Bufan, Biljana, Živković, Irena, Prijić, Ivana, Stoiljković, Vera, Leposavić, Gordana, "Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine" in Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th (2019),
https://hdl.handle.net/21.15107/rcub_intor_692 .

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Bufan, Biljana
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/534
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
EP  - 496
IS  - 4
SP  - 475
VL  - 20
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",
pages = "496-475",
number = "4",
volume = "20",
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  - Milovanović, Vladimir
AU  - Dimitrijević, Ljiljana
AU  - Petrušić, Vladimir
AU  - Kadrić, Jasminka
AU  - Minić, Rajna
AU  - Živković, Irena
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/500
AB  - During time, both professionals and general public became aware of the importance of animal welfare. This term not only covers endangered wild animal species, animals used in food industry, pets and experimental animals, but also animals used in production of biologics. The implementation of the 3R concept (Replacement, Reduction and Refinement) is especially important in this type of production. In this article, we describe for the first time the low dose, low volume and multi-site immunization protocol, as well as appropriate ELISA we developed for production of European anti-viper (V. ammodytes, long horned) antivenom in horses, which can help to significantly improve the welfare of the used animals.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria - Beograd
T1  - Application of the 3r concept in the production of European antiviperinum on horses - multisite, low volumes immunization protocol and Elisa
EP  - 419
IS  - 4
SP  - 401
VL  - 68
DO  - 10.2478/acve-2018-0033
ER  - 

@article{
author = "Milovanović, Vladimir and Dimitrijević, Ljiljana and Petrušić, Vladimir and Kadrić, Jasminka and Minić, Rajna and Živković, Irena",
year = "2018",
abstract = "During time, both professionals and general public became aware of the importance of animal welfare. This term not only covers endangered wild animal species, animals used in food industry, pets and experimental animals, but also animals used in production of biologics. The implementation of the 3R concept (Replacement, Reduction and Refinement) is especially important in this type of production. In this article, we describe for the first time the low dose, low volume and multi-site immunization protocol, as well as appropriate ELISA we developed for production of European anti-viper (V. ammodytes, long horned) antivenom in horses, which can help to significantly improve the welfare of the used animals.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria - Beograd",
title = "Application of the 3r concept in the production of European antiviperinum on horses - multisite, low volumes immunization protocol and Elisa",
pages = "419-401",
number = "4",
volume = "68",
doi = "10.2478/acve-2018-0033"
}

Milovanović, V., Dimitrijević, L., Petrušić, V., Kadrić, J., Minić, R.,& Živković, I.. (2018). Application of the 3r concept in the production of European antiviperinum on horses - multisite, low volumes immunization protocol and Elisa. in Acta veterinaria - Beograd
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 68(4), 401-419.
https://doi.org/10.2478/acve-2018-0033

Milovanović V, Dimitrijević L, Petrušić V, Kadrić J, Minić R, Živković I. Application of the 3r concept in the production of European antiviperinum on horses - multisite, low volumes immunization protocol and Elisa. in Acta veterinaria - Beograd. 2018;68(4):401-419.
doi:10.2478/acve-2018-0033 .

Milovanović, Vladimir, Dimitrijević, Ljiljana, Petrušić, Vladimir, Kadrić, Jasminka, Minić, Rajna, Živković, Irena, "Application of the 3r concept in the production of European antiviperinum on horses - multisite, low volumes immunization protocol and Elisa" in Acta veterinaria - Beograd, 68, no. 4 (2018):401-419,
https://doi.org/10.2478/acve-2018-0033 . .

TY  - JOUR
AU  - Minić, Rajna
AU  - Papić, Zlatko
AU  - Đorđević, Brižita
AU  - Michalickova, Danica
AU  - Ilić, Vesna
AU  - Mathiesen, Geir
AU  - Živković, Irena
AU  - Pantić, Visnja
AU  - Dimitrijević, Ljiljana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/508
AB  - The goal of this work was to elucidate similarities between microorganisms from the perspective of the humoral immune system reactivity in professional athletes. The reactivity of serum IgG of 14 young, individuals was analyzed to 23 selected microorganisms as antigens by use of the in house ELISA. Serum IgM and IgA reactivity was also analyzed and a control group of sex and age matched individuals was used for comparison. The obtained absorbance levels were used as a string of values to correlate the reactivity to different microorganisms. IgM was found to be the most cross reactive antibody class, Pearson's r = 0.7 +/- 0.92, for very distant bacterial species such as Lactobacillus and E. coli. High correlation in IgG levels was found for Gammaproteobacteria and LPS (from E. coli) (r = 0.77 for LPS vs. P. aeruginosa to r = 0.98 for LPS vs. E. coli), whereas this correlation was lower in the control group (r = 0.49 for LPS vs. P. aeruginosa to r = 0.66 for LPS vs. E. coli). The correlation was also analyzed between total IgG and IgG subclasses specific for the same microorganism, and IgG2 was identified as the main subclass recognising different microorganisms, as well as recognising LPS. Upon correlation of IgG with IgA for the same microorganism absence of or negative correlation was found between bacteria-specific IgA and IgG in case of Lactobacillus and Staphylococcusgeni, whereas correlation was absent or positive for Candida albicans, Enterococcusfaecalis, Streptococcus species tested in professional athletes. Opposite results were obtained for the control group. Outlined here is a simple experimental procedure and data analysis which yields functional significance and which can be used for determining the similarities between microorganisms from the aspect of the humoral immune system, for determining the main IgG subclass involved in an immune response as well as for the analysis of different target populations.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Profiling of microorganism-binding serum antibody specificities in professional athletes
IS  - 9
VL  - 13
DO  - 10.1371/journal.pone.0203665
ER  - 

@article{
author = "Minić, Rajna and Papić, Zlatko and Đorđević, Brižita and Michalickova, Danica and Ilić, Vesna and Mathiesen, Geir and Živković, Irena and Pantić, Visnja and Dimitrijević, Ljiljana",
year = "2018",
abstract = "The goal of this work was to elucidate similarities between microorganisms from the perspective of the humoral immune system reactivity in professional athletes. The reactivity of serum IgG of 14 young, individuals was analyzed to 23 selected microorganisms as antigens by use of the in house ELISA. Serum IgM and IgA reactivity was also analyzed and a control group of sex and age matched individuals was used for comparison. The obtained absorbance levels were used as a string of values to correlate the reactivity to different microorganisms. IgM was found to be the most cross reactive antibody class, Pearson's r = 0.7 +/- 0.92, for very distant bacterial species such as Lactobacillus and E. coli. High correlation in IgG levels was found for Gammaproteobacteria and LPS (from E. coli) (r = 0.77 for LPS vs. P. aeruginosa to r = 0.98 for LPS vs. E. coli), whereas this correlation was lower in the control group (r = 0.49 for LPS vs. P. aeruginosa to r = 0.66 for LPS vs. E. coli). The correlation was also analyzed between total IgG and IgG subclasses specific for the same microorganism, and IgG2 was identified as the main subclass recognising different microorganisms, as well as recognising LPS. Upon correlation of IgG with IgA for the same microorganism absence of or negative correlation was found between bacteria-specific IgA and IgG in case of Lactobacillus and Staphylococcusgeni, whereas correlation was absent or positive for Candida albicans, Enterococcusfaecalis, Streptococcus species tested in professional athletes. Opposite results were obtained for the control group. Outlined here is a simple experimental procedure and data analysis which yields functional significance and which can be used for determining the similarities between microorganisms from the aspect of the humoral immune system, for determining the main IgG subclass involved in an immune response as well as for the analysis of different target populations.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Profiling of microorganism-binding serum antibody specificities in professional athletes",
number = "9",
volume = "13",
doi = "10.1371/journal.pone.0203665"
}

Minić, R., Papić, Z., Đorđević, B., Michalickova, D., Ilić, V., Mathiesen, G., Živković, I., Pantić, V.,& Dimitrijević, L.. (2018). Profiling of microorganism-binding serum antibody specificities in professional athletes. in PLoS One
Public Library Science, San Francisco., 13(9).
https://doi.org/10.1371/journal.pone.0203665

Minić R, Papić Z, Đorđević B, Michalickova D, Ilić V, Mathiesen G, Živković I, Pantić V, Dimitrijević L. Profiling of microorganism-binding serum antibody specificities in professional athletes. in PLoS One. 2018;13(9).
doi:10.1371/journal.pone.0203665 .

Minić, Rajna, Papić, Zlatko, Đorđević, Brižita, Michalickova, Danica, Ilić, Vesna, Mathiesen, Geir, Živković, Irena, Pantić, Visnja, Dimitrijević, Ljiljana, "Profiling of microorganism-binding serum antibody specificities in professional athletes" in PLoS One, 13, no. 9 (2018),
https://doi.org/10.1371/journal.pone.0203665 . .

TY  - CONF
AU  - Minić, Rajna
AU  - Papić, Zlatko
AU  - Đorđević, Brižita
AU  - Michalickova, Danica
AU  - Ilić, Vesna
AU  - Mathiesen, Geir
AU  - Živković, Irena
AU  - Dimitrijević, Ljiljana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/507
PB  - Lippincott Williams & Wilkins, Philadelphia
C3  - Journal of Clinical Gastroenterology
T1  - Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes
EP  - S99
SP  - S99
VL  - 52
UR  - https://hdl.handle.net/21.15107/rcub_intor_507
ER  - 

@conference{
author = "Minić, Rajna and Papić, Zlatko and Đorđević, Brižita and Michalickova, Danica and Ilić, Vesna and Mathiesen, Geir and Živković, Irena and Dimitrijević, Ljiljana",
year = "2018",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Journal of Clinical Gastroenterology",
title = "Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes",
pages = "S99-S99",
volume = "52",
url = "https://hdl.handle.net/21.15107/rcub_intor_507"
}

Minić, R., Papić, Z., Đorđević, B., Michalickova, D., Ilić, V., Mathiesen, G., Živković, I.,& Dimitrijević, L.. (2018). Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes. in Journal of Clinical Gastroenterology
Lippincott Williams & Wilkins, Philadelphia., 52, S99-S99.
https://hdl.handle.net/21.15107/rcub_intor_507

Minić R, Papić Z, Đorđević B, Michalickova D, Ilić V, Mathiesen G, Živković I, Dimitrijević L. Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes. in Journal of Clinical Gastroenterology. 2018;52:S99-S99.
https://hdl.handle.net/21.15107/rcub_intor_507 .

Minić, Rajna, Papić, Zlatko, Đorđević, Brižita, Michalickova, Danica, Ilić, Vesna, Mathiesen, Geir, Živković, Irena, Dimitrijević, Ljiljana, "Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes" in Journal of Clinical Gastroenterology, 52 (2018):S99-S99,
https://hdl.handle.net/21.15107/rcub_intor_507 .

TY  - JOUR
AU  - Mrkić, Ivan
AU  - Minić, Rajna
AU  - Popović, Dragan M.
AU  - Živković, Irena
AU  - Gavrović-Jankulović, Marija
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2887
UR  - http://intor.torlakinstitut.com/handle/123456789/646
AB  - Aim To investigate the immunomodulatory potential of a chimera composed of the receptor-binding domain of hemagglutinin 1 (H1s) from Influenza virus and Der p 2 (D2) allergen for allergen-specific immunotherapy of house-dust mite allergy (HDM). Main methods: H1sD2 chimera and D2 allergen were produced by genetic engineering in E. coli. Recombinant antigens were extracted from inclusion bodies by urea, then refolded and purified by immobilized-metal affinity chromatography (IMAC). Purity was verified by 2D-PAGE and secondary structures were assessed by CD spectroscopy. IgE reactivity of H1sD2 and D2 was tested in western blot with sera from 8 persons with clinical history of HDM allergy. Immunogenicity of H1sD2 and D2 were analyzed in Balb/c mice. Cytokine profile was analyzed by ELISA after stimulation of mouse spleen cells with H1sD2 and D2. Leukocyte population abundance of cells isolated from spleen and lymph node was assessed by flow cytometry. Key findings: Purified recombinant proteins H1sD2 (42 kDa) and D2 (15 kDa) revealed well defined secondary structures, and preserved IgE reactive epitopes. Analysis of supernatants of mouse spleen cells after stimulation with H1sD2 and D2, revealed a qualitatively different cytokine profile from H1sD2 immunized mouse cells (increase in IL10). CD8+ cells were decreased in the lymph node of D2 immunized mice, whereas H1sD2 immunization led to an increase of CD8+ cells in both the lymph node and the spleen. Significance: H1sD2 chimera attenuates Der p 2-inherent Th2 response and directs the immune response toward Th1 and Treg phenotype.
PB  - Elsevier
T2  - Life Sciences
T1  - Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy
EP  - 165
SP  - 158
VL  - 213
DO  - 10.1016/j.lfs.2018.10.036
ER  - 

@article{
author = "Mrkić, Ivan and Minić, Rajna and Popović, Dragan M. and Živković, Irena and Gavrović-Jankulović, Marija",
year = "2018",
abstract = "Aim To investigate the immunomodulatory potential of a chimera composed of the receptor-binding domain of hemagglutinin 1 (H1s) from Influenza virus and Der p 2 (D2) allergen for allergen-specific immunotherapy of house-dust mite allergy (HDM). Main methods: H1sD2 chimera and D2 allergen were produced by genetic engineering in E. coli. Recombinant antigens were extracted from inclusion bodies by urea, then refolded and purified by immobilized-metal affinity chromatography (IMAC). Purity was verified by 2D-PAGE and secondary structures were assessed by CD spectroscopy. IgE reactivity of H1sD2 and D2 was tested in western blot with sera from 8 persons with clinical history of HDM allergy. Immunogenicity of H1sD2 and D2 were analyzed in Balb/c mice. Cytokine profile was analyzed by ELISA after stimulation of mouse spleen cells with H1sD2 and D2. Leukocyte population abundance of cells isolated from spleen and lymph node was assessed by flow cytometry. Key findings: Purified recombinant proteins H1sD2 (42 kDa) and D2 (15 kDa) revealed well defined secondary structures, and preserved IgE reactive epitopes. Analysis of supernatants of mouse spleen cells after stimulation with H1sD2 and D2, revealed a qualitatively different cytokine profile from H1sD2 immunized mouse cells (increase in IL10). CD8+ cells were decreased in the lymph node of D2 immunized mice, whereas H1sD2 immunization led to an increase of CD8+ cells in both the lymph node and the spleen. Significance: H1sD2 chimera attenuates Der p 2-inherent Th2 response and directs the immune response toward Th1 and Treg phenotype.",
publisher = "Elsevier",
journal = "Life Sciences",
title = "Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy",
pages = "165-158",
volume = "213",
doi = "10.1016/j.lfs.2018.10.036"
}

Mrkić, I., Minić, R., Popović, D. M., Živković, I.,& Gavrović-Jankulović, M.. (2018). Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy. in Life Sciences
Elsevier., 213, 158-165.
https://doi.org/10.1016/j.lfs.2018.10.036

Mrkić I, Minić R, Popović DM, Živković I, Gavrović-Jankulović M. Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy. in Life Sciences. 2018;213:158-165.
doi:10.1016/j.lfs.2018.10.036 .

Mrkić, Ivan, Minić, Rajna, Popović, Dragan M., Živković, Irena, Gavrović-Jankulović, Marija, "Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy" in Life Sciences, 213 (2018):158-165,
https://doi.org/10.1016/j.lfs.2018.10.036 . .

TY  - JOUR
AU  - Živković, Irena
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Petrušić, Vladimir
AU  - Minić, Rajna
AU  - Bufan, Biljana
AU  - Popović, Olga
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/522
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
EP  - 24
SP  - 18
VL  - 52
DO  - 10.1016/j.biologicals.2018.01.007
ER  - 

@article{
author = "Živković, Irena and Petrović, Raisa and Arsenović-Ranin, Nevena and Petrušić, 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",
pages = "24-18",
volume = "52",
doi = "10.1016/j.biologicals.2018.01.007"
}

Živković, I., Petrović, R., Arsenović-Ranin, N., Petrušić, 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, Petrušić 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, Petrušić, 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  - Mrkić, Ivan
AU  - Minić, Rajna
AU  - Popović, Dragan
AU  - Živković, Irena
AU  - Gavrović-Jankulović, Marija
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/515
AB  - Aim To investigate the immunomodulatory potential of a chimera composed of the receptor-binding domain of hemagglutinin 1 (H1s) from Influenza virus and Der p 2 (D2) allergen for allergen-specific immunotherapy of house-dust mite allergy (HDM). Main methods: H1sD2 chimera and D2 allergen were produced by genetic engineering in E. coli. Recombinant antigens were extracted from inclusion bodies by urea, then refolded and purified by immobilized-metal affinity chromatography (IMAC). Purity was verified by 2D-PAGE and secondary structures were assessed by CD spectroscopy. IgE reactivity of H1sD2 and D2 was tested in western blot with sera from 8 persons with clinical history of HDM allergy. Immunogenicity of H1sD2 and D2 were analyzed in Balb/c mice. Cytokine profile was analyzed by ELISA after stimulation of mouse spleen cells with H1sD2 and D2. Leukocyte population abundance of cells isolated from spleen and lymph node was assessed by flow cytometry. Key findings: Purified recombinant proteins H1sD2 (42 kDa) and D2 (15 kDa) revealed well defined secondary structures, and preserved IgE reactive epitopes. Analysis of supernatants of mouse spleen cells after stimulation with H1sD2 and D2, revealed a qualitatively different cytokine profile from H1sD2 immunized mouse cells (increase in IL10). CD8+ cells were decreased in the lymph node of D2 immunized mice, whereas H1sD2 immunization led to an increase of CD8+ cells in both the lymph node and the spleen. Significance: H1sD2 chimera attenuates Der p 2-inherent Th2 response and directs the immune response toward Th1 and Treg phenotype.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Life Sciences
T1  - Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy
EP  - 165
SP  - 158
VL  - 213
DO  - 10.1016/j.lfs.2018.10.036
ER  - 

@article{
author = "Mrkić, Ivan and Minić, Rajna and Popović, Dragan and Živković, Irena and Gavrović-Jankulović, Marija",
year = "2018",
abstract = "Aim To investigate the immunomodulatory potential of a chimera composed of the receptor-binding domain of hemagglutinin 1 (H1s) from Influenza virus and Der p 2 (D2) allergen for allergen-specific immunotherapy of house-dust mite allergy (HDM). Main methods: H1sD2 chimera and D2 allergen were produced by genetic engineering in E. coli. Recombinant antigens were extracted from inclusion bodies by urea, then refolded and purified by immobilized-metal affinity chromatography (IMAC). Purity was verified by 2D-PAGE and secondary structures were assessed by CD spectroscopy. IgE reactivity of H1sD2 and D2 was tested in western blot with sera from 8 persons with clinical history of HDM allergy. Immunogenicity of H1sD2 and D2 were analyzed in Balb/c mice. Cytokine profile was analyzed by ELISA after stimulation of mouse spleen cells with H1sD2 and D2. Leukocyte population abundance of cells isolated from spleen and lymph node was assessed by flow cytometry. Key findings: Purified recombinant proteins H1sD2 (42 kDa) and D2 (15 kDa) revealed well defined secondary structures, and preserved IgE reactive epitopes. Analysis of supernatants of mouse spleen cells after stimulation with H1sD2 and D2, revealed a qualitatively different cytokine profile from H1sD2 immunized mouse cells (increase in IL10). CD8+ cells were decreased in the lymph node of D2 immunized mice, whereas H1sD2 immunization led to an increase of CD8+ cells in both the lymph node and the spleen. Significance: H1sD2 chimera attenuates Der p 2-inherent Th2 response and directs the immune response toward Th1 and Treg phenotype.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Life Sciences",
title = "Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy",
pages = "165-158",
volume = "213",
doi = "10.1016/j.lfs.2018.10.036"
}

Mrkić, I., Minić, R., Popović, D., Živković, I.,& Gavrović-Jankulović, M.. (2018). Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy. in Life Sciences
Pergamon-Elsevier Science Ltd, Oxford., 213, 158-165.
https://doi.org/10.1016/j.lfs.2018.10.036

Mrkić I, Minić R, Popović D, Živković I, Gavrović-Jankulović M. Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy. in Life Sciences. 2018;213:158-165.
doi:10.1016/j.lfs.2018.10.036 .

Mrkić, Ivan, Minić, Rajna, Popović, Dragan, Živković, Irena, Gavrović-Jankulović, Marija, "Newly designed hemagglutinin-Der p 2 chimera is a potential candidate for allergen specific immunotherapy" in Life Sciences, 213 (2018):158-165,
https://doi.org/10.1016/j.lfs.2018.10.036 . .

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  - http://intor.torlakinstitut.com/handle/123456789/501
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
EP  - 126
SP  - 117
VL  - 207
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",
pages = "126-117",
volume = "207",
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  - CONF
AU  - Živković, Irena
AU  - Milovanović, Vladimir
AU  - Stojanović, Milan
AU  - Stanković, Aleksandra
AU  - Minić, Rajna
AU  - Dimitrijević, Ljiljana
PY  - 2017
UR  - http://intor.torlakinstitut.com/handle/123456789/713
AB  - Poznato je da 3R koncept u radu sa eksperimentalnim životinjama označava: smanjenje broja korišćenih životinja (Reduction), zamenu testova na
životinjama in vitro metodama (Replacement) i poboljšanje tretmana i
manipulacije (Refinement). Ovaj koncept je uspešno primenjen u postupku
produkcije zmijskog protivotrova (antivenoma) u Institutu za virusologiju,
vakcine i serume "Torlak".
Životinje izbora za imunizaciju u proizvodnji antivenoma su često konji
zbog mogućnosti produkcije velike (komercijalne) količine antivenoma što
se ne može lako postići na malim životinjama. Jedan od najvažnijih koraka u
produkciji antivenoma je imunizacija otrovom (venomom) na takav način
da se u organizmu životinje indukuje dugotrajan i visok titar specifičnih
antitela. Standardni imunizacioni protokol podrazumevao je injektovanje
velike količine emulzifikovanog otrova na jedno mesto, što je stvaralo
granulome i/ili rane na mestu ubrizgavanja. Novom šemom imunizacije,
aplikacijom male količine emulzije na mnogo mesta, ovakve neželjene
pojave su prestale ili postale zanemarljive (Refinement).
Nova šema imunizacije podrazumeva primenu doktrine "Mala doza, mala
količina-zapremina, mnogo mesta injektovanja" (" Low dose, low volume,
multi-site immunization "). Na taj način se smanjuje potreba za velikom
količinom otrova, zbog što posledično dovodi do smanjenja potrebe za
nabavkom velikog broja zmija, smanjenja rada sa zmijama, kao i smanjenja
opasnosti za radnika koji radi sa zmijama u više aspekata (kraći rad, manji
umor, smanjena šansa za eksces). Nova šema imunizacije je ujedno poboljšala titar antitela, a time povećala količinu antiseruma koja se može
produkovati u jednom konju, što dalje dovodi do smanjenja broja konja
potrebnih za imunizaciju (Reduction).
Paralelno sa razvijanjem nove imunizacione šeme, u laboratoriji je razvijen
ELISA test za detekciju IgG antitela specifičnih za venom. Indukcija i
povećanje specifičnih antitela, standardno se prati testom potence na
miševima, kojim se meri koliku zaštitu produkovan konjski antiserum pruža
miševima koji su primili letalnu dozu otrova. Pokazali smo da ELISA test može da zameni test potence tokom imunizacionog perioda i perioda
održavanja titra (Replacement).
Novi imunizacioni protokol i razvijen laboratorijski metod za praćenje
kinetike specifičnih antivenom antitela, omogućili su ne samo pojednostavljenje produkcionog postupka i povećanje prinosa proizvoda, već i
znatno poboljšanje dobrobiti eksperimentalnih životinja, naročito konja.
Ovako uspešan pristup konceptu 3R može se primeniti i u proizvodnji
drugih imunih seruma na konjima.
PB  - Univerzitet u Beogradu, Fakultet veterinarske medicine
C3  - Sedmo regionalno Savetovanje uzgoj, reprodukcija i zdravstvena zaštita konja, Zbornik predavanja, Ljubičevo
T1  - Primena koncepta 3r u produkciji antivenoma na konjima
EP  - 118
SP  - 117
UR  - https://hdl.handle.net/21.15107/rcub_intor_713
ER  - 

@conference{
author = "Živković, Irena and Milovanović, Vladimir and Stojanović, Milan and Stanković, Aleksandra and Minić, Rajna and Dimitrijević, Ljiljana",
year = "2017",
abstract = "Poznato je da 3R koncept u radu sa eksperimentalnim životinjama označava: smanjenje broja korišćenih životinja (Reduction), zamenu testova na
životinjama in vitro metodama (Replacement) i poboljšanje tretmana i
manipulacije (Refinement). Ovaj koncept je uspešno primenjen u postupku
produkcije zmijskog protivotrova (antivenoma) u Institutu za virusologiju,
vakcine i serume "Torlak".
Životinje izbora za imunizaciju u proizvodnji antivenoma su često konji
zbog mogućnosti produkcije velike (komercijalne) količine antivenoma što
se ne može lako postići na malim životinjama. Jedan od najvažnijih koraka u
produkciji antivenoma je imunizacija otrovom (venomom) na takav način
da se u organizmu životinje indukuje dugotrajan i visok titar specifičnih
antitela. Standardni imunizacioni protokol podrazumevao je injektovanje
velike količine emulzifikovanog otrova na jedno mesto, što je stvaralo
granulome i/ili rane na mestu ubrizgavanja. Novom šemom imunizacije,
aplikacijom male količine emulzije na mnogo mesta, ovakve neželjene
pojave su prestale ili postale zanemarljive (Refinement).
Nova šema imunizacije podrazumeva primenu doktrine "Mala doza, mala
količina-zapremina, mnogo mesta injektovanja" (" Low dose, low volume,
multi-site immunization "). Na taj način se smanjuje potreba za velikom
količinom otrova, zbog što posledično dovodi do smanjenja potrebe za
nabavkom velikog broja zmija, smanjenja rada sa zmijama, kao i smanjenja
opasnosti za radnika koji radi sa zmijama u više aspekata (kraći rad, manji
umor, smanjena šansa za eksces). Nova šema imunizacije je ujedno poboljšala titar antitela, a time povećala količinu antiseruma koja se može
produkovati u jednom konju, što dalje dovodi do smanjenja broja konja
potrebnih za imunizaciju (Reduction).
Paralelno sa razvijanjem nove imunizacione šeme, u laboratoriji je razvijen
ELISA test za detekciju IgG antitela specifičnih za venom. Indukcija i
povećanje specifičnih antitela, standardno se prati testom potence na
miševima, kojim se meri koliku zaštitu produkovan konjski antiserum pruža
miševima koji su primili letalnu dozu otrova. Pokazali smo da ELISA test može da zameni test potence tokom imunizacionog perioda i perioda
održavanja titra (Replacement).
Novi imunizacioni protokol i razvijen laboratorijski metod za praćenje
kinetike specifičnih antivenom antitela, omogućili su ne samo pojednostavljenje produkcionog postupka i povećanje prinosa proizvoda, već i
znatno poboljšanje dobrobiti eksperimentalnih životinja, naročito konja.
Ovako uspešan pristup konceptu 3R može se primeniti i u proizvodnji
drugih imunih seruma na konjima.",
publisher = "Univerzitet u Beogradu, Fakultet veterinarske medicine",
journal = "Sedmo regionalno Savetovanje uzgoj, reprodukcija i zdravstvena zaštita konja, Zbornik predavanja, Ljubičevo",
title = "Primena koncepta 3r u produkciji antivenoma na konjima",
pages = "118-117",
url = "https://hdl.handle.net/21.15107/rcub_intor_713"
}

Živković, I., Milovanović, V., Stojanović, M., Stanković, A., Minić, R.,& Dimitrijević, L.. (2017). Primena koncepta 3r u produkciji antivenoma na konjima. in Sedmo regionalno Savetovanje uzgoj, reprodukcija i zdravstvena zaštita konja, Zbornik predavanja, Ljubičevo
Univerzitet u Beogradu, Fakultet veterinarske medicine., 117-118.
https://hdl.handle.net/21.15107/rcub_intor_713

Živković I, Milovanović V, Stojanović M, Stanković A, Minić R, Dimitrijević L. Primena koncepta 3r u produkciji antivenoma na konjima. in Sedmo regionalno Savetovanje uzgoj, reprodukcija i zdravstvena zaštita konja, Zbornik predavanja, Ljubičevo. 2017;:117-118.
https://hdl.handle.net/21.15107/rcub_intor_713 .

Živković, Irena, Milovanović, Vladimir, Stojanović, Milan, Stanković, Aleksandra, Minić, Rajna, Dimitrijević, Ljiljana, "Primena koncepta 3r u produkciji antivenoma na konjima" in Sedmo regionalno Savetovanje uzgoj, reprodukcija i zdravstvena zaštita konja, Zbornik predavanja, Ljubičevo (2017):117-118,
https://hdl.handle.net/21.15107/rcub_intor_713 .

TY  - JOUR
AU  - Milošević, Milena
AU  - Milićević, Katarina
AU  - Božić, Iva
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Bijelić, Dunja
AU  - Dubaić, Marija
AU  - Živković, Irena
AU  - Stević, Zorica
AU  - Giniatullin, Rashid
AU  - Anđus, Pavle
PY  - 2017
UR  - http://intor.torlakinstitut.com/handle/123456789/482
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-alpha and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2-0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Immunology
T1  - Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line
VL  - 8
DO  - 10.3389/fimmu.2017.01619
ER  - 

@article{
author = "Milošević, Milena and Milićević, Katarina and Božić, Iva and Lavrnja, Irena and Stevanović, Ivana and Bijelić, Dunja and Dubaić, Marija and Živković, Irena and Stević, Zorica and Giniatullin, Rashid and Anđus, Pavle",
year = "2017",
abstract = "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-alpha and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2-0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Immunology",
title = "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line",
volume = "8",
doi = "10.3389/fimmu.2017.01619"
}

Milošević, M., Milićević, K., Božić, I., Lavrnja, I., Stevanović, I., Bijelić, D., Dubaić, M., Živković, I., Stević, Z., Giniatullin, R.,& Anđus, P.. (2017). Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology
Frontiers Media Sa, Lausanne., 8.
https://doi.org/10.3389/fimmu.2017.01619

Milošević M, Milićević K, Božić I, Lavrnja I, Stevanović I, Bijelić D, Dubaić M, Živković I, Stević Z, Giniatullin R, Anđus P. Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology. 2017;8.
doi:10.3389/fimmu.2017.01619 .

Milošević, Milena, Milićević, Katarina, Božić, Iva, Lavrnja, Irena, Stevanović, Ivana, Bijelić, Dunja, Dubaić, Marija, Živković, Irena, Stević, Zorica, Giniatullin, Rashid, Anđus, Pavle, "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation Antioxidative System in BV-2 Microglial Cell Line" in Frontiers in Immunology, 8 (2017),
https://doi.org/10.3389/fimmu.2017.01619 . .