TY  - JOUR
AU  - Božić, Dragana
AU  - Bufan, Biljana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5603
AB  - Antibacterial vaccines play a central role in modern medicine by providing an effective approach to
combating infectious diseases caused by bacteria. The importance of these vaccines lies in their ability to
stimulate the immune system to recognise and neutralise bacterial pathogens, or exotoxins produced by them,
thereby preventing, or mitigating the severity of bacterial infections. The development and widespread use of
antibacterial vaccines have contributed significantly to reducing the global burden of diseases such as pneumonia,
meningitis, and sepsis.
Today, the global increase in vaccine-preventable diseases is a worrying trend that is closely linked to the
emergence and advocacy of anti-vaccination policies. According to the latest World Health Organisation report,
vaccination coverage in Serbia has declined over the past decade, jeopardising the collective immunity and led to
recent outbreaks of vaccine-preventable diseases such as whooping cough and measles. Understanding the
significance of antibacterial vaccines underscores their importance in promoting individual and community immunity,
which ultimately leads to a healthier population and the prevention of antibiotic resistance.
This paper summarises the main characteristics of the different types of antibacterial vaccines, such as whole cell
vaccines, subunit vaccines and toxoid vaccines, and provides an overview of the types of bacterial antigens
contained in vaccines available for mandatory immunisation (vaccines against tuberculosis, diphtheria, tetanus,
pertussis, Haemophilus influenzae and pneumoccus) or for non-mandatory immunisation (meningococcal vaccine,
typhoid vaccine, cholera vaccine).
AB  - Antibakterijske vakcine igraju glavnu ulogu u savremenoj medicini obezbeđujući efikasan pristup u borbi protiv
zaraznih bolesti izazvanih bakterijama. Važnost ovih vakcina leži u njihovoj sposobnosti da stimulišu imunski sistem
da prepozna i neutrališe bakterijske patogene, ili egzotoksine koje oni proizvode, čime sprečavaju ili ublažavaju
ozbiljnost bakterijskih infekcija. Razvoj i široka upotreba antibakterijskih vakcina značajno su doprineli smanjenju
globalnog tereta bolesti kao što su pneumonija, meningitis i sepsa.
Danas je globalni porast bolesti koje se mogu sprečiti vakcinama zabrinjavajući trend koji je usko povezan sa
pojavom i zagovaranjem politike protiv vakcinacije. Prema poslednjem izveštaju Svetske zdravstvene organizacije,
pokrivenost vakcinacijom u Srbiji je opala tokom protekle decenije, što je ugrozilo kolektivni imunitet i dovelo do
nedavnih izbijanja bolesti koje se mogu sprečiti vakcinom, poput velikog kašlja i malih boginja. Razumevanje
značaja antibakterijskih vakcina naglašava njihov značaj u promovisanju imuniteta pojedinca i zajednice, što na
kraju dovodi do zdravije populacije i prevencije rezistencije na antibiotike.
Ovaj rad sumira glavne karakteristike različitih tipova antibakterijskih vakcina, kao što su celo ćelijske vakcine,
podjedinične vakcine i toksoidne vakcine, i daje pregled tipova bakterijskih antigena sadržanih u vakcinama
dostupnim za obaveznu imunizaciju (vakcine protiv tuberkuloze, difterije, tetanusa, pertusisa, Haemophilus
influenzae i pneumoka) ili za neobaveznu imunizaciju (vakcina protiv meningokoka, tifusa i kolere).
PB  - Udruženja za preventivnu pedijatriju Srbije
T2  - Preventive Paediatrics Journal of the Association for Preventive Pediatrics of Serbia / Preventivna pedijatrija Časopis Udruženja za preventivnu pedijatriju Srbije
T1  - An overview of current vacccines for the prophylaxis of bacterical infections Pres
T1  - Pregled aktuelnih vakcina za profilaksu bakterijskih infekcija
VL  - 10
IS  - 1-2
SP  - 19
EP  - 26
DO  - 10.46793/PP240214004B
DO  - 10.46793/PP240214004B
ER  - 

@article{
author = "Božić, Dragana and Bufan, Biljana",
year = "2024",
abstract = "Antibacterial vaccines play a central role in modern medicine by providing an effective approach to
combating infectious diseases caused by bacteria. The importance of these vaccines lies in their ability to
stimulate the immune system to recognise and neutralise bacterial pathogens, or exotoxins produced by them,
thereby preventing, or mitigating the severity of bacterial infections. The development and widespread use of
antibacterial vaccines have contributed significantly to reducing the global burden of diseases such as pneumonia,
meningitis, and sepsis.
Today, the global increase in vaccine-preventable diseases is a worrying trend that is closely linked to the
emergence and advocacy of anti-vaccination policies. According to the latest World Health Organisation report,
vaccination coverage in Serbia has declined over the past decade, jeopardising the collective immunity and led to
recent outbreaks of vaccine-preventable diseases such as whooping cough and measles. Understanding the
significance of antibacterial vaccines underscores their importance in promoting individual and community immunity,
which ultimately leads to a healthier population and the prevention of antibiotic resistance.
This paper summarises the main characteristics of the different types of antibacterial vaccines, such as whole cell
vaccines, subunit vaccines and toxoid vaccines, and provides an overview of the types of bacterial antigens
contained in vaccines available for mandatory immunisation (vaccines against tuberculosis, diphtheria, tetanus,
pertussis, Haemophilus influenzae and pneumoccus) or for non-mandatory immunisation (meningococcal vaccine,
typhoid vaccine, cholera vaccine)., Antibakterijske vakcine igraju glavnu ulogu u savremenoj medicini obezbeđujući efikasan pristup u borbi protiv
zaraznih bolesti izazvanih bakterijama. Važnost ovih vakcina leži u njihovoj sposobnosti da stimulišu imunski sistem
da prepozna i neutrališe bakterijske patogene, ili egzotoksine koje oni proizvode, čime sprečavaju ili ublažavaju
ozbiljnost bakterijskih infekcija. Razvoj i široka upotreba antibakterijskih vakcina značajno su doprineli smanjenju
globalnog tereta bolesti kao što su pneumonija, meningitis i sepsa.
Danas je globalni porast bolesti koje se mogu sprečiti vakcinama zabrinjavajući trend koji je usko povezan sa
pojavom i zagovaranjem politike protiv vakcinacije. Prema poslednjem izveštaju Svetske zdravstvene organizacije,
pokrivenost vakcinacijom u Srbiji je opala tokom protekle decenije, što je ugrozilo kolektivni imunitet i dovelo do
nedavnih izbijanja bolesti koje se mogu sprečiti vakcinom, poput velikog kašlja i malih boginja. Razumevanje
značaja antibakterijskih vakcina naglašava njihov značaj u promovisanju imuniteta pojedinca i zajednice, što na
kraju dovodi do zdravije populacije i prevencije rezistencije na antibiotike.
Ovaj rad sumira glavne karakteristike različitih tipova antibakterijskih vakcina, kao što su celo ćelijske vakcine,
podjedinične vakcine i toksoidne vakcine, i daje pregled tipova bakterijskih antigena sadržanih u vakcinama
dostupnim za obaveznu imunizaciju (vakcine protiv tuberkuloze, difterije, tetanusa, pertusisa, Haemophilus
influenzae i pneumoka) ili za neobaveznu imunizaciju (vakcina protiv meningokoka, tifusa i kolere).",
publisher = "Udruženja za preventivnu pedijatriju Srbije",
journal = "Preventive Paediatrics Journal of the Association for Preventive Pediatrics of Serbia / Preventivna pedijatrija Časopis Udruženja za preventivnu pedijatriju Srbije",
title = "An overview of current vacccines for the prophylaxis of bacterical infections Pres, Pregled aktuelnih vakcina za profilaksu bakterijskih infekcija",
volume = "10",
number = "1-2",
pages = "19-26",
doi = "10.46793/PP240214004B, 10.46793/PP240214004B"
}

Božić, D.,& Bufan, B.. (2024). An overview of current vacccines for the prophylaxis of bacterical infections Pres. in Preventive Paediatrics Journal of the Association for Preventive Pediatrics of Serbia / Preventivna pedijatrija Časopis Udruženja za preventivnu pedijatriju Srbije
Udruženja za preventivnu pedijatriju Srbije., 10(1-2), 19-26.
https://doi.org/10.46793/PP240214004B

Božić D, Bufan B. An overview of current vacccines for the prophylaxis of bacterical infections Pres. in Preventive Paediatrics Journal of the Association for Preventive Pediatrics of Serbia / Preventivna pedijatrija Časopis Udruženja za preventivnu pedijatriju Srbije. 2024;10(1-2):19-26.
doi:10.46793/PP240214004B .

Božić, Dragana, Bufan, Biljana, "An overview of current vacccines for the prophylaxis of bacterical infections Pres" in Preventive Paediatrics Journal of the Association for Preventive Pediatrics of Serbia / Preventivna pedijatrija Časopis Udruženja za preventivnu pedijatriju Srbije, 10, no. 1-2 (2024):19-26,
https://doi.org/10.46793/PP240214004B . .

TY  - JOUR
AU  - Božić, Dragana
AU  - Milenković, Marina
AU  - Antić-Stanković, Jelena
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5582
AB  - The normal human microbiota, formerly called the "microbial flora," consists of bacteria,
fungi, viruses, and parasites that colonise the skin and mucous membranes of the respiratory,
gastrointestinal, and genitourinary tracts. The number and diversity of microorganisms varies
between different body niches and is greatest in the intestinal tract. The microbiota contributes to
the homeostasis of the human organism by preventing colonisation by pathogenic
microorganisms, participating in digestive processes and metabolism, and regulating immune
functions.
Various environmental and genetic factors can lead to an imbalance in the human
microbiota, called dysbiosis, which can affect human health. Dysbiosis is usually the result of
decreased microbial diversity and a lower number of saprophytic microorganisms, followed by
an overgrowth of opportunistic species. The most common diseases directly related to intestinal
dysbiosis are antibiotic-associated diarrhoea and pseudomembranous colitis, both of which are
associated with the excessive growth of harmful bacteria and Clostridioides difficile following
broad-spectrum antibiotic therapy.
Dysbiosis is associated with various health conditions or diseases such as acne, psoriasis,
eczema, chronic obstructive pulmonary disease, inflammatory bowel disease, obesity, metabolic
syndrome, type 2 diabetes, autoimmune diseases and allergies, neurological diseases such as
Parkinson's disease, Alzheimer's disease, epilepsy and stroke, depression, anxiety, infertility,
preterm birth, and malignancies.
AB  - Normalna ljudska mikrobiota, koja se ranije nazivala „mikroflora“, sastoji se od bakterija,
gljivica, virusa i parazita koji kolonizuju kožu i sluzokožu respiratornog, gastrointestinalnog i
genitourinarnog trakta. Broj i raznovrsnost mikroorganizama variraju između različitih telesnih
niša i najveći su u crevnom traktu. Mikrobiota doprinosi homeostazi ljudskog organizma tako što
sprečava kolonizaciju patogenim mikroorganizmima, učestvuje u procesima varenja i
metabolizma i reguliše imunološke funkcije.
Disbioza je stanje u kome dolazi do neravnoteže sastava mikrobiote usled uticaja različitih
egzogenih ili endogenih faktora, što može uticati na ljudsko zdravlje. Ona je najčešće rezultat
smanjene raznovrsnosti mikroorganizama i manjeg broja saprofitnih bakterija, što je praćeno
prekomernim rastom potencijalno štetnih vrsta. Najčešće bolesti koje su direktno povezane sa
crevnom disbiozom su dijareja povezana sa primenom antibiotika i pseudomembranozni kolitis,
a obe nastaju kao posledica prekomernog rasta štetnih bakterija i Clostridioides difficile nakon
terapije antibioticima širokog spektra.
Disbioza je povezana sa različitim zdravstvenim stanjima ili bolestima kao što su akne,
psorijaza, ekcem, hronična opstruktivna bolest pluća, inflamatorna bolest creva, gojaznost,
metabolički sindrom, dijabetes tipa 2, autoimunske bolesti i alergije, neurološke bolesti kao što
su Parkinsonova bolest, Alchajmerova demencija, epilepsija i moždani udar, depresija,
anksioznost, neplodnost, prevremeni porođaj i maligni tumori.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
PB  - Beograd : Univerzitet u Beogradu - Farmaceutski fakultet
T2  - Arhiv za farmaciju
T1  - Normal human microbiota and dysbiosis - implications for health and disease
T1  - Normalna ljudska mikrobiota i disbioza - implikacije po zdravlje i bolest
VL  - 74
IS  - 1
SP  - 1
EP  - 22
DO  - 10.5937/arhfarm74-46612
ER  - 

@article{
author = "Božić, Dragana and Milenković, Marina and Antić-Stanković, Jelena and Arsenović-Ranin, Nevena and Bufan, Biljana",
year = "2024",
abstract = "The normal human microbiota, formerly called the "microbial flora," consists of bacteria,
fungi, viruses, and parasites that colonise the skin and mucous membranes of the respiratory,
gastrointestinal, and genitourinary tracts. The number and diversity of microorganisms varies
between different body niches and is greatest in the intestinal tract. The microbiota contributes to
the homeostasis of the human organism by preventing colonisation by pathogenic
microorganisms, participating in digestive processes and metabolism, and regulating immune
functions.
Various environmental and genetic factors can lead to an imbalance in the human
microbiota, called dysbiosis, which can affect human health. Dysbiosis is usually the result of
decreased microbial diversity and a lower number of saprophytic microorganisms, followed by
an overgrowth of opportunistic species. The most common diseases directly related to intestinal
dysbiosis are antibiotic-associated diarrhoea and pseudomembranous colitis, both of which are
associated with the excessive growth of harmful bacteria and Clostridioides difficile following
broad-spectrum antibiotic therapy.
Dysbiosis is associated with various health conditions or diseases such as acne, psoriasis,
eczema, chronic obstructive pulmonary disease, inflammatory bowel disease, obesity, metabolic
syndrome, type 2 diabetes, autoimmune diseases and allergies, neurological diseases such as
Parkinson's disease, Alzheimer's disease, epilepsy and stroke, depression, anxiety, infertility,
preterm birth, and malignancies., Normalna ljudska mikrobiota, koja se ranije nazivala „mikroflora“, sastoji se od bakterija,
gljivica, virusa i parazita koji kolonizuju kožu i sluzokožu respiratornog, gastrointestinalnog i
genitourinarnog trakta. Broj i raznovrsnost mikroorganizama variraju između različitih telesnih
niša i najveći su u crevnom traktu. Mikrobiota doprinosi homeostazi ljudskog organizma tako što
sprečava kolonizaciju patogenim mikroorganizmima, učestvuje u procesima varenja i
metabolizma i reguliše imunološke funkcije.
Disbioza je stanje u kome dolazi do neravnoteže sastava mikrobiote usled uticaja različitih
egzogenih ili endogenih faktora, što može uticati na ljudsko zdravlje. Ona je najčešće rezultat
smanjene raznovrsnosti mikroorganizama i manjeg broja saprofitnih bakterija, što je praćeno
prekomernim rastom potencijalno štetnih vrsta. Najčešće bolesti koje su direktno povezane sa
crevnom disbiozom su dijareja povezana sa primenom antibiotika i pseudomembranozni kolitis,
a obe nastaju kao posledica prekomernog rasta štetnih bakterija i Clostridioides difficile nakon
terapije antibioticima širokog spektra.
Disbioza je povezana sa različitim zdravstvenim stanjima ili bolestima kao što su akne,
psorijaza, ekcem, hronična opstruktivna bolest pluća, inflamatorna bolest creva, gojaznost,
metabolički sindrom, dijabetes tipa 2, autoimunske bolesti i alergije, neurološke bolesti kao što
su Parkinsonova bolest, Alchajmerova demencija, epilepsija i moždani udar, depresija,
anksioznost, neplodnost, prevremeni porođaj i maligni tumori.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije, Beograd : Univerzitet u Beogradu - Farmaceutski fakultet",
journal = "Arhiv za farmaciju",
title = "Normal human microbiota and dysbiosis - implications for health and disease, Normalna ljudska mikrobiota i disbioza - implikacije po zdravlje i bolest",
volume = "74",
number = "1",
pages = "1-22",
doi = "10.5937/arhfarm74-46612"
}

Božić, D., Milenković, M., Antić-Stanković, J., Arsenović-Ranin, N.,& Bufan, B.. (2024). Normal human microbiota and dysbiosis - implications for health and disease. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 74(1), 1-22.
https://doi.org/10.5937/arhfarm74-46612

Božić D, Milenković M, Antić-Stanković J, Arsenović-Ranin N, Bufan B. Normal human microbiota and dysbiosis - implications for health and disease. in Arhiv za farmaciju. 2024;74(1):1-22.
doi:10.5937/arhfarm74-46612 .

Božić, Dragana, Milenković, Marina, Antić-Stanković, Jelena, Arsenović-Ranin, Nevena, Bufan, Biljana, "Normal human microbiota and dysbiosis - implications for health and disease" in Arhiv za farmaciju, 74, no. 1 (2024):1-22,
https://doi.org/10.5937/arhfarm74-46612 . .

TY  - CONF
AU  - Mitrović, Jelena
AU  - Ilić, Tanja
AU  - Jančić, Ivan
AU  - Bufan, Biljana
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5090
AB  - Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration
Jelena Mitrović1, Tanja Ilić1, Ivan Jančić2, Biljana Bufan2, Miroslav Savić3, Snežana Savić1
1 Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
2 Department of Microbiology and Immunology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
3 Department of Pharmacology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
Estimation of endotoxin level in parenteral formulations is a prerequisite for numerous in vitro tests in preclinical studies and for future clinical development. However, the Limulus amoebocyte lysate (LAL) test in formulations containing nanoparticles could often lead to misinterpretation of results. Therefore, we tested if endotoxins could be detected in nanocrystal dispersions by the commercial gel clot assay kit. Nanocrystals of DK-I-56-1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one) were prepared by wet-ball milling, lyophilized and reconstituted with water for injection prior experiment. Different dilutions of nanocrystal dispersion in LAL reagent water were prepared as well as positive and negative control. Despite difficulties to detect gel clots, they were visible in the sample at dilutions 1:75 and below. According to the protocol, the endotoxin limit was estimated to be 25.00 EU/ml, which corresponds to <12.50 EU/mg of DK-I-56-1. This value relates to the endotoxin limit for diazepam, with the similar dosing regimen as proposed for DK-I-56-1.
C3  - NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland
T1  - Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5090
ER  - 

@conference{
author = "Mitrović, Jelena and Ilić, Tanja and Jančić, Ivan and Bufan, Biljana and Savić, Miroslav and Savić, Snežana",
year = "2023",
abstract = "Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration
Jelena Mitrović1, Tanja Ilić1, Ivan Jančić2, Biljana Bufan2, Miroslav Savić3, Snežana Savić1
1 Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
2 Department of Microbiology and Immunology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
3 Department of Pharmacology, University of Belgrade – Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
Estimation of endotoxin level in parenteral formulations is a prerequisite for numerous in vitro tests in preclinical studies and for future clinical development. However, the Limulus amoebocyte lysate (LAL) test in formulations containing nanoparticles could often lead to misinterpretation of results. Therefore, we tested if endotoxins could be detected in nanocrystal dispersions by the commercial gel clot assay kit. Nanocrystals of DK-I-56-1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one) were prepared by wet-ball milling, lyophilized and reconstituted with water for injection prior experiment. Different dilutions of nanocrystal dispersion in LAL reagent water were prepared as well as positive and negative control. Despite difficulties to detect gel clots, they were visible in the sample at dilutions 1:75 and below. According to the protocol, the endotoxin limit was estimated to be 25.00 EU/ml, which corresponds to <12.50 EU/mg of DK-I-56-1. This value relates to the endotoxin limit for diazepam, with the similar dosing regimen as proposed for DK-I-56-1.",
journal = "NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland",
title = "Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5090"
}

Mitrović, J., Ilić, T., Jančić, I., Bufan, B., Savić, M.,& Savić, S.. (2023). Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration. in NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland.
https://hdl.handle.net/21.15107/rcub_farfar_5090

Mitrović J, Ilić T, Jančić I, Bufan B, Savić M, Savić S. Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration. in NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_5090 .

Mitrović, Jelena, Ilić, Tanja, Jančić, Ivan, Bufan, Biljana, Savić, Miroslav, Savić, Snežana, "Estimation of endotoxin level in nanocrystal dispersion of DK-I-56-1 intended for parenteral administration" in NANOGVA Symposium, October 5th - 6th, 2023, Geneva, Switzerland (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5090 .

TY  - JOUR
AU  - Božić, Dragana
AU  - Ćirković, Ivana
AU  - Milovanović, Jovica
AU  - Bufan, Biljana
AU  - Folić, Miljan
AU  - Savić Vujović, Katarina
AU  - Pavlović, Bojan
AU  - Jotić, Ana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5341
AB  - Bacterial biofilms play an important role in the pathogenesis of chronic upper respiratory tract infections. In addition to conventional antimicrobial therapy, N-acetyl-L-cysteine (NAC) and propolis are dietary supplements that are often recommended as supportive therapy for upper respiratory tract infections. However, no data on the beneficial effect of their combination against bacterial biofilms can be found in the scientific literature. Therefore, the aim of our study was to investigate the in vitro effect of N-acetyl-L-cysteine (NAC) and dry propolis extract in fixed combinations (NAC/dry propolis extract fixed combination) on biofilm formation by bacterial species isolated from patients with chronic rhinosinusitis, chronic otitis media, and chronic adenoiditis. The prospective study included 48 adults with chronic rhinosinusitis, 29 adults with chronic otitis media, and 33 children with chronic adenoiditis. Bacteria were isolated from tissue samples obtained intraoperatively and identified using the MALDI-TOF Vitek MS System. The antimicrobial activity, synergism, and antibiofilm effect of NAC/dry propolis extract fixed combination were studied in vitro. A total of 116 different strains were isolated from the tissue samples, with staphylococci being the most frequently isolated in all patients (57.8%). MICs of the NAC/dry propolis extract fixed combination ranged from 1.25/0.125 to 20/2 mg NAC/mg propolis. A synergistic effect (FICI ≤ 0.5) was observed in 51.7% of strains. The majority of isolates from patients with chronic otitis media were moderate biofilm producers and in chronic adenoiditis they were weak biofilm producers, while the same number of isolates in patients with chronic rhinosinusitis were weak and moderate biofilm producers. Subinhibitory concentrations of the NAC/propolis combination ranging from 0.625–0.156 mg/mL to 10–2.5 mg/mL of NAC combined with 0.062–0.016 mg/mL to 1–0.25 mg/mL of propolis inhibited biofilm formation in all bacterial strains. Suprainhibitory concentrations ranging from 2.5–10 mg/mL to 40–160 mg/mL of NAC in combination with 0.25–1 mg/mL to 4–16 mg/mL of propolis completely eradicated the biofilm. In conclusion, the fixed combination of NAC and dry propolis extract has a synergistic effect on all stages of biofilm formation and eradication of the formed biofilm in bacteria isolated from upper respiratory tract infections.
PB  - MDPI
T2  - Pharmaceuticals
T1  - In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections
VL  - 16
IS  - 11
DO  - 10.3390/ph16111604
ER  - 

@article{
author = "Božić, Dragana and Ćirković, Ivana and Milovanović, Jovica and Bufan, Biljana and Folić, Miljan and Savić Vujović, Katarina and Pavlović, Bojan and Jotić, Ana",
year = "2023",
abstract = "Bacterial biofilms play an important role in the pathogenesis of chronic upper respiratory tract infections. In addition to conventional antimicrobial therapy, N-acetyl-L-cysteine (NAC) and propolis are dietary supplements that are often recommended as supportive therapy for upper respiratory tract infections. However, no data on the beneficial effect of their combination against bacterial biofilms can be found in the scientific literature. Therefore, the aim of our study was to investigate the in vitro effect of N-acetyl-L-cysteine (NAC) and dry propolis extract in fixed combinations (NAC/dry propolis extract fixed combination) on biofilm formation by bacterial species isolated from patients with chronic rhinosinusitis, chronic otitis media, and chronic adenoiditis. The prospective study included 48 adults with chronic rhinosinusitis, 29 adults with chronic otitis media, and 33 children with chronic adenoiditis. Bacteria were isolated from tissue samples obtained intraoperatively and identified using the MALDI-TOF Vitek MS System. The antimicrobial activity, synergism, and antibiofilm effect of NAC/dry propolis extract fixed combination were studied in vitro. A total of 116 different strains were isolated from the tissue samples, with staphylococci being the most frequently isolated in all patients (57.8%). MICs of the NAC/dry propolis extract fixed combination ranged from 1.25/0.125 to 20/2 mg NAC/mg propolis. A synergistic effect (FICI ≤ 0.5) was observed in 51.7% of strains. The majority of isolates from patients with chronic otitis media were moderate biofilm producers and in chronic adenoiditis they were weak biofilm producers, while the same number of isolates in patients with chronic rhinosinusitis were weak and moderate biofilm producers. Subinhibitory concentrations of the NAC/propolis combination ranging from 0.625–0.156 mg/mL to 10–2.5 mg/mL of NAC combined with 0.062–0.016 mg/mL to 1–0.25 mg/mL of propolis inhibited biofilm formation in all bacterial strains. Suprainhibitory concentrations ranging from 2.5–10 mg/mL to 40–160 mg/mL of NAC in combination with 0.25–1 mg/mL to 4–16 mg/mL of propolis completely eradicated the biofilm. In conclusion, the fixed combination of NAC and dry propolis extract has a synergistic effect on all stages of biofilm formation and eradication of the formed biofilm in bacteria isolated from upper respiratory tract infections.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections",
volume = "16",
number = "11",
doi = "10.3390/ph16111604"
}

Božić, D., Ćirković, I., Milovanović, J., Bufan, B., Folić, M., Savić Vujović, K., Pavlović, B.,& Jotić, A.. (2023). In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections. in Pharmaceuticals
MDPI., 16(11).
https://doi.org/10.3390/ph16111604

Božić D, Ćirković I, Milovanović J, Bufan B, Folić M, Savić Vujović K, Pavlović B, Jotić A. In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections. in Pharmaceuticals. 2023;16(11).
doi:10.3390/ph16111604 .

Božić, Dragana, Ćirković, Ivana, Milovanović, Jovica, Bufan, Biljana, Folić, Miljan, Savić Vujović, Katarina, Pavlović, Bojan, Jotić, Ana, "In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections" in Pharmaceuticals, 16, no. 11 (2023),
https://doi.org/10.3390/ph16111604 . .

TY  - JOUR
AU  - Vekić, Jelena
AU  - Vujčić, Sanja
AU  - Bufan, Biljana
AU  - Bojanin, Dragana
AU  - Al-Hashmi, Khamis
AU  - Al-Rasadi, Khaild
AU  - Stoian, Anca Pantea
AU  - Zeljković, Aleksandra
AU  - Rizzo, Manfredi
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4415
AB  - Disorders of lipoprotein metabolism and glucose homeostasis are common consequences of insulin resistance and usually co-segregate in patients with metabolic syndrome and type 2 diabetes mellitus (DM). Insulin-resistant subjects are characterized by atherogenic dyslipidemia, a specific lipid pattern which includes hypertriglyceridemia, reduced high-density lipoprotein cholesterol level, and increased proportion of small, dense low-density lipoprotein (LDL). Chronic hyperglycemia favors the processes of non-enzymatic glycation, leading to the increased production of advanced glycation end products (AGEs). Apart from direct harmful effects, AGEs are also potent inducers of oxidative stress and inflammation. In addition, increased AGEs’ production may induce further qualitative modifications of small, dense LDL particles, converting them to glycated LDLs. These particles are even more atherogenic and may confer an increased cardiovascular risk. In this narrative review, we summarize the available evidence of the pathophysiological role and clinical importance of circulating AGEs and glycated LDLs in patients with dyslipidemia, particularly those with DM and related complications. In addition, we discuss recent advances and the issues that should be improved regarding laboratory assessment of AGEs and glycated LDLs, as well as the possibilities for their therapeutic modulation.
PB  - MDPI
T2  - Metabolites
T1  - The Role of Advanced Glycation End Products on Dyslipidemia
VL  - 13
IS  - 1
DO  - 10.3390/metabo13010077
ER  - 

@article{
author = "Vekić, Jelena and Vujčić, Sanja and Bufan, Biljana and Bojanin, Dragana and Al-Hashmi, Khamis and Al-Rasadi, Khaild and Stoian, Anca Pantea and Zeljković, Aleksandra and Rizzo, Manfredi",
year = "2023",
abstract = "Disorders of lipoprotein metabolism and glucose homeostasis are common consequences of insulin resistance and usually co-segregate in patients with metabolic syndrome and type 2 diabetes mellitus (DM). Insulin-resistant subjects are characterized by atherogenic dyslipidemia, a specific lipid pattern which includes hypertriglyceridemia, reduced high-density lipoprotein cholesterol level, and increased proportion of small, dense low-density lipoprotein (LDL). Chronic hyperglycemia favors the processes of non-enzymatic glycation, leading to the increased production of advanced glycation end products (AGEs). Apart from direct harmful effects, AGEs are also potent inducers of oxidative stress and inflammation. In addition, increased AGEs’ production may induce further qualitative modifications of small, dense LDL particles, converting them to glycated LDLs. These particles are even more atherogenic and may confer an increased cardiovascular risk. In this narrative review, we summarize the available evidence of the pathophysiological role and clinical importance of circulating AGEs and glycated LDLs in patients with dyslipidemia, particularly those with DM and related complications. In addition, we discuss recent advances and the issues that should be improved regarding laboratory assessment of AGEs and glycated LDLs, as well as the possibilities for their therapeutic modulation.",
publisher = "MDPI",
journal = "Metabolites",
title = "The Role of Advanced Glycation End Products on Dyslipidemia",
volume = "13",
number = "1",
doi = "10.3390/metabo13010077"
}

Vekić, J., Vujčić, S., Bufan, B., Bojanin, D., Al-Hashmi, K., Al-Rasadi, K., Stoian, A. P., Zeljković, A.,& Rizzo, M.. (2023). The Role of Advanced Glycation End Products on Dyslipidemia. in Metabolites
MDPI., 13(1).
https://doi.org/10.3390/metabo13010077

Vekić J, Vujčić S, Bufan B, Bojanin D, Al-Hashmi K, Al-Rasadi K, Stoian AP, Zeljković A, Rizzo M. The Role of Advanced Glycation End Products on Dyslipidemia. in Metabolites. 2023;13(1).
doi:10.3390/metabo13010077 .

Vekić, Jelena, Vujčić, Sanja, Bufan, Biljana, Bojanin, Dragana, Al-Hashmi, Khamis, Al-Rasadi, Khaild, Stoian, Anca Pantea, Zeljković, Aleksandra, Rizzo, Manfredi, "The Role of Advanced Glycation End Products on Dyslipidemia" in Metabolites, 13, no. 1 (2023),
https://doi.org/10.3390/metabo13010077 . .

TY  - CONF
AU  - Ćuruvija, Ivana
AU  - Bufan, Biljana
AU  - Đorović, Emilija
AU  - Blagojević, Veljko
AU  - Grujić-Milanović, Jelica
AU  - Marković, Milica
AU  - Đuretić, Jasmina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5132
AB  - Aims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal 
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated 
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE. 
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing 
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti 
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry. 
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of 
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency, 
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal 
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was 
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats 
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and 
IL-1β expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater 
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more 
pronounced in aged than in young rats.
PB  - Federation of European Neuroscience Societies (FENS)
C3  - FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts
T1  - Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis
SP  - S05-250
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5132
ER  - 

@conference{
author = "Ćuruvija, Ivana and Bufan, Biljana and Đorović, Emilija and Blagojević, Veljko and Grujić-Milanović, Jelica and Marković, Milica and Đuretić, Jasmina",
year = "2022",
abstract = "Aims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal 
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated 
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE. 
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing 
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti 
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry. 
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of 
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency, 
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal 
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was 
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats 
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and 
IL-1β expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater 
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more 
pronounced in aged than in young rats.",
publisher = "Federation of European Neuroscience Societies (FENS)",
journal = "FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts",
title = "Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis",
pages = "S05-250",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5132"
}

Ćuruvija, I., Bufan, B., Đorović, E., Blagojević, V., Grujić-Milanović, J., Marković, M.,& Đuretić, J.. (2022). Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis. in FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts
Federation of European Neuroscience Societies (FENS)., S05-250.
https://hdl.handle.net/21.15107/rcub_farfar_5132

Ćuruvija I, Bufan B, Đorović E, Blagojević V, Grujić-Milanović J, Marković M, Đuretić J. Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis. in FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts. 2022;:S05-250.
https://hdl.handle.net/21.15107/rcub_farfar_5132 .

Ćuruvija, Ivana, Bufan, Biljana, Đorović, Emilija, Blagojević, Veljko, Grujić-Milanović, Jelica, Marković, Milica, Đuretić, Jasmina, "Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis" in FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts (2022):S05-250,
https://hdl.handle.net/21.15107/rcub_farfar_5132 .

TY  - JOUR
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Živković, Irena
AU  - Petrović, Raisa
AU  - Leposavić, Gordana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4109
AB  - Aims: Given that deprivation of noradrenaline acting on lymphocytes through β-adrenoceptor influences anti- body 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 prolif- eration 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 Inc.
T2  - Life Sciences
T1  - B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor
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 anti- body 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 prolif- eration 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 Inc.",
journal = "Life Sciences",
title = "B-cell response to seasonal influenza vaccine in mice is amenable to pharmacological modulation through β-adrenoceptor",
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 Inc.., 301.
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.
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),
https://doi.org/10.1016/j.lfs.2022.120617 . .

TY  - JOUR
AU  - Đuretić, Jasmina
AU  - Bufan, Biljana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3857
AB  - Elderly patients with rheumatoid arthritis, psoriasis and psoriatic arthritis encompass those with elderly-onset disease, over 60 years of age, but also those with earlier disease onset who entered old age. Considering the age-related changes of the immune system, possible frailty, susceptibility  to  infection  and  concomitant  comorbidity  that  implies  multiple  medicines,  the treatment of these diseases in elderly patients can be challenging. Interleukin inhibitors have been shown to be an efficient and safe treatment for these diseases. However, elderly patients with these  diseases  were  often  included  in  the  pivotal  clinical  trials  for  interleukin  inhibitors  in numbers insufficient to determine whether they responded differently from younger subjects. The aim of this paper was to review the findings on the efficacy and safety of interleukin inhibitor treatment  in  elderly  patients  with  rheumatoid  arthritis,  psoriasis,  and  psoriatic  arthritis.The findings suggest that, for all the interleukin inhibitors reviewed herein, used in elderly patients with rheumatoid arthritis, or with psoriasis and psoriatic arthritis, the efficacy was comparable to younger patients. Furthermore, the incidence of reported adverse events was similar in these two age groups. Severe adverse events, which were related to sarilumab treatment for rheumatoid arthritis and secukinumab treatment for psoriasis, were higher in elderly patients.The reviewed findings suggest that the interleukin inhibitors approved and currently in use in clinical practice for the treatment of rheumatoid arthritis, psoriasis, and psoriatic arthritis can be considered a safe and efficient option for these diseases in elderly patients.
AB  - Stariji pacijenti koji boluju od reumatoidnog artritisa, psorijaze ili psorijaznog artritisa uključuju one kod kojih je bolest imala kasni početak, nakon 60. godine starosti, ali takođe i one pacijente kod kojih je bolest počela ranije, a koji su ušli u staro doba. Imajući u vidu starenjem uslovljene promene imunskog sistema, moguću slabost starijih, podložnost infekcijama, prateći komorbiditet, koji uključuje i uzimanje više lekova, terapija ovih bolesti kod starijih pacijenata može predstavljati izazov. Inhibitori interleukina su se pokazali kao efikasna i bezbedna terapija ovih poremećaja. Međutim, stariji pacijenti sa ovim bolestima su često bili nedovoljno zastupljeni u ključnim kliničkim ispitivanjima inhibitora interleukina da bi se moglo sa sigurnošću utvrditi da postoji razlika u terapijskom odgovoru kod ovih pacijenata u odnosu na isti kod mlađih pacijenata. Cilj ovog rada bio je da prikaže nalaze od značaja za bezbednost i efikasnost terapije inhibitorima interleukina kod starijih pacijenata sa reumatoidnim artritisom, psorijazom ili psorijaznim artritisom. Nalazi ukazuju da je efikasnost inhibitora interleukina, prikazanih u ovom radu, uporediva kod starijih i mlađih pacijenata. Osim toga, incidencija neželjenih događaja se nije razlikovala između ove dve starosne grupe. Veća incidencija teških neželjenih događaja kod starijih pacijenata u odnosu na mlađe bila je zabeležena u terapiji reumatoidnog artritisa sarilumabom i psorijaze secukinumabom. Terapija reumatoidnog artritisa, psorijaze i psorijaznog artritisa inhibitorima interleukina može se smatrati efikasnom i bezbednom u populaciji starih pacijenata.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Safety and efficacy of interleukin inhibitors in elderly patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis
T1  - Bezbednost i efikasnost inhibitora interleukina u terapiji reumatoidnog artritisa, psorijaze i psorijaznog artritisa u populaciji starih osoba
VL  - 71
IS  - 2
SP  - 101
EP  - 119
DO  - 10.5937/arhfarm71-30505
ER  - 

@article{
author = "Đuretić, Jasmina and Bufan, Biljana",
year = "2021",
abstract = "Elderly patients with rheumatoid arthritis, psoriasis and psoriatic arthritis encompass those with elderly-onset disease, over 60 years of age, but also those with earlier disease onset who entered old age. Considering the age-related changes of the immune system, possible frailty, susceptibility  to  infection  and  concomitant  comorbidity  that  implies  multiple  medicines,  the treatment of these diseases in elderly patients can be challenging. Interleukin inhibitors have been shown to be an efficient and safe treatment for these diseases. However, elderly patients with these  diseases  were  often  included  in  the  pivotal  clinical  trials  for  interleukin  inhibitors  in numbers insufficient to determine whether they responded differently from younger subjects. The aim of this paper was to review the findings on the efficacy and safety of interleukin inhibitor treatment  in  elderly  patients  with  rheumatoid  arthritis,  psoriasis,  and  psoriatic  arthritis.The findings suggest that, for all the interleukin inhibitors reviewed herein, used in elderly patients with rheumatoid arthritis, or with psoriasis and psoriatic arthritis, the efficacy was comparable to younger patients. Furthermore, the incidence of reported adverse events was similar in these two age groups. Severe adverse events, which were related to sarilumab treatment for rheumatoid arthritis and secukinumab treatment for psoriasis, were higher in elderly patients.The reviewed findings suggest that the interleukin inhibitors approved and currently in use in clinical practice for the treatment of rheumatoid arthritis, psoriasis, and psoriatic arthritis can be considered a safe and efficient option for these diseases in elderly patients., Stariji pacijenti koji boluju od reumatoidnog artritisa, psorijaze ili psorijaznog artritisa uključuju one kod kojih je bolest imala kasni početak, nakon 60. godine starosti, ali takođe i one pacijente kod kojih je bolest počela ranije, a koji su ušli u staro doba. Imajući u vidu starenjem uslovljene promene imunskog sistema, moguću slabost starijih, podložnost infekcijama, prateći komorbiditet, koji uključuje i uzimanje više lekova, terapija ovih bolesti kod starijih pacijenata može predstavljati izazov. Inhibitori interleukina su se pokazali kao efikasna i bezbedna terapija ovih poremećaja. Međutim, stariji pacijenti sa ovim bolestima su često bili nedovoljno zastupljeni u ključnim kliničkim ispitivanjima inhibitora interleukina da bi se moglo sa sigurnošću utvrditi da postoji razlika u terapijskom odgovoru kod ovih pacijenata u odnosu na isti kod mlađih pacijenata. Cilj ovog rada bio je da prikaže nalaze od značaja za bezbednost i efikasnost terapije inhibitorima interleukina kod starijih pacijenata sa reumatoidnim artritisom, psorijazom ili psorijaznim artritisom. Nalazi ukazuju da je efikasnost inhibitora interleukina, prikazanih u ovom radu, uporediva kod starijih i mlađih pacijenata. Osim toga, incidencija neželjenih događaja se nije razlikovala između ove dve starosne grupe. Veća incidencija teških neželjenih događaja kod starijih pacijenata u odnosu na mlađe bila je zabeležena u terapiji reumatoidnog artritisa sarilumabom i psorijaze secukinumabom. Terapija reumatoidnog artritisa, psorijaze i psorijaznog artritisa inhibitorima interleukina može se smatrati efikasnom i bezbednom u populaciji starih pacijenata.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Safety and efficacy of interleukin inhibitors in elderly patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis, Bezbednost i efikasnost inhibitora interleukina u terapiji reumatoidnog artritisa, psorijaze i psorijaznog artritisa u populaciji starih osoba",
volume = "71",
number = "2",
pages = "101-119",
doi = "10.5937/arhfarm71-30505"
}

Đuretić, J.,& Bufan, B.. (2021). Safety and efficacy of interleukin inhibitors in elderly patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 71(2), 101-119.
https://doi.org/10.5937/arhfarm71-30505

Đuretić J, Bufan B. Safety and efficacy of interleukin inhibitors in elderly patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis. in Arhiv za farmaciju. 2021;71(2):101-119.
doi:10.5937/arhfarm71-30505 .

Đuretić, Jasmina, Bufan, Biljana, "Safety and efficacy of interleukin inhibitors in elderly patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis" in Arhiv za farmaciju, 71, no. 2 (2021):101-119,
https://doi.org/10.5937/arhfarm71-30505 . .

TY  - CONF
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Petrović, Raisa
AU  - Živković, Irena
AU  - Leposavić, Gordana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4725
AB  - The study was undertaken considering importance of antibody response for influenza vaccine efficacy and data indicating that β2‐adrenoceptor stimulation may affect antibody generation. To elucidate influence of β‐adrenoceptor‐mediated signaling on antibody response to QIV, serum titers of QIV‐specific IgG and draining lymph node and splenic germinal center (GC) reaction to QIV were examined in BALB/c mice treated with propranolol, non‐selective β‐adrenoceptor blocker, or vehicle (controls) daily, beginning two days before immunization. Four weeks after immunization IgG antibody titer was decreased in propranolol‐treated mice. This correlated with lower frequency of GC B cells in lymphoid organs of propranolol‐treated mice, and their diminished proliferation upon restimulation with QIV antigens in culture. Consistently, Tfh/Tfr cell ratio was shifted towards the latter in propranolol‐treated mice. This correlated with lower frequency of QIV‐specific CD4+ cells that produce IL‐21, the key regulator of GC reaction, in lymphoid organs of propranolol‐ 
treated mice, as suggested by in vitro recall test. Additionally, propranolol treatment shifted IgG1/IgG2a antibody ratio towards IgG1 antibody (contributing mainly to the virus clearance). This was consistent with the shift in IFN‐γ/IL‐4 ratio to the site of IL‐4 in QIV‐stimulated splenocyte cultures from propranolol‐treated mice compared with controls. Thus, the study suggests that chronic administration of propranolol, drug widely used for cardiovascular pathology, and recently repurposed for several other pathologies, including cancer, rheumatoid arthritis, and anxiety may impair efficacy of QIV by affecting CD4+ T‐cell cytokine secretory profile and thereby overall efficacy of Tfh help to B cells, and its influence on IgG subclass switching pattern.
C3  - European Journal of Immunology
T1  - β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice
VL  - 51
IS  - Suppl.1
SP  - 305
EP  - 305
DO  - 10.1002/eji.202170200
ER  - 

@conference{
author = "Bufan, Biljana and Arsenović-Ranin, Nevena and Petrović, Raisa and Živković, Irena and Leposavić, Gordana",
year = "2021",
abstract = "The study was undertaken considering importance of antibody response for influenza vaccine efficacy and data indicating that β2‐adrenoceptor stimulation may affect antibody generation. To elucidate influence of β‐adrenoceptor‐mediated signaling on antibody response to QIV, serum titers of QIV‐specific IgG and draining lymph node and splenic germinal center (GC) reaction to QIV were examined in BALB/c mice treated with propranolol, non‐selective β‐adrenoceptor blocker, or vehicle (controls) daily, beginning two days before immunization. Four weeks after immunization IgG antibody titer was decreased in propranolol‐treated mice. This correlated with lower frequency of GC B cells in lymphoid organs of propranolol‐treated mice, and their diminished proliferation upon restimulation with QIV antigens in culture. Consistently, Tfh/Tfr cell ratio was shifted towards the latter in propranolol‐treated mice. This correlated with lower frequency of QIV‐specific CD4+ cells that produce IL‐21, the key regulator of GC reaction, in lymphoid organs of propranolol‐ 
treated mice, as suggested by in vitro recall test. Additionally, propranolol treatment shifted IgG1/IgG2a antibody ratio towards IgG1 antibody (contributing mainly to the virus clearance). This was consistent with the shift in IFN‐γ/IL‐4 ratio to the site of IL‐4 in QIV‐stimulated splenocyte cultures from propranolol‐treated mice compared with controls. Thus, the study suggests that chronic administration of propranolol, drug widely used for cardiovascular pathology, and recently repurposed for several other pathologies, including cancer, rheumatoid arthritis, and anxiety may impair efficacy of QIV by affecting CD4+ T‐cell cytokine secretory profile and thereby overall efficacy of Tfh help to B cells, and its influence on IgG subclass switching pattern.",
journal = "European Journal of Immunology",
title = "β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice",
volume = "51",
number = "Suppl.1",
pages = "305-305",
doi = "10.1002/eji.202170200"
}

Bufan, B., Arsenović-Ranin, N., Petrović, R., Živković, I.,& Leposavić, G.. (2021). β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice. in European Journal of Immunology, 51(Suppl.1), 305-305.
https://doi.org/10.1002/eji.202170200

Bufan B, Arsenović-Ranin N, Petrović R, Živković I, Leposavić G. β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice. in European Journal of Immunology. 2021;51(Suppl.1):305-305.
doi:10.1002/eji.202170200 .

Bufan, Biljana, Arsenović-Ranin, Nevena, Petrović, Raisa, Živković, Irena, Leposavić, Gordana, "β‐adrenoceptor blockade affects the germinal center B cell response to seasonal quadrivalent inactivated influenza vaccine (QIV) in mice" in European Journal of Immunology, 51, no. Suppl.1 (2021):305-305,
https://doi.org/10.1002/eji.202170200 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
AU  - Nacka-Aleksić, Mirjana
AU  - Kosec, Dušan
AU  - Pilipović, Ivan
AU  - Kotur-Stevuljević, Jelena
AU  - Simić, Ljubica
AU  - Sopta, Jelena
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3714
AB  - Monocytes’ plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43lowCD11b+ and CCR2-CX3CR1+CD43hiCD11b+ cells (corresponding to “classical” and “non-classical” monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.
PB  - Springer Nature
T2  - Inflammation
T1  - Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats
VL  - 43
IS  - 6
SP  - 2312
EP  - 2331
DO  - 10.1007/s10753-020-01302-0
ER  - 

@article{
author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Bufan, Biljana and Nacka-Aleksić, Mirjana and Kosec, Dušan and Pilipović, Ivan and Kotur-Stevuljević, Jelena and Simić, Ljubica and Sopta, Jelena and Leposavić, Gordana",
year = "2020",
abstract = "Monocytes’ plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43lowCD11b+ and CCR2-CX3CR1+CD43hiCD11b+ cells (corresponding to “classical” and “non-classical” monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1β (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.",
publisher = "Springer Nature",
journal = "Inflammation",
title = "Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats",
volume = "43",
number = "6",
pages = "2312-2331",
doi = "10.1007/s10753-020-01302-0"
}

Dimitrijević, M., Arsenović-Ranin, N., Bufan, B., Nacka-Aleksić, M., Kosec, D., Pilipović, I., Kotur-Stevuljević, J., Simić, L., Sopta, J.,& Leposavić, G.. (2020). Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats. in Inflammation
Springer Nature., 43(6), 2312-2331.
https://doi.org/10.1007/s10753-020-01302-0

Dimitrijević M, Arsenović-Ranin N, Bufan B, Nacka-Aleksić M, Kosec D, Pilipović I, Kotur-Stevuljević J, Simić L, Sopta J, Leposavić G. Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats. in Inflammation. 2020;43(6):2312-2331.
doi:10.1007/s10753-020-01302-0 .

Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Bufan, Biljana, Nacka-Aleksić, Mirjana, Kosec, Dušan, Pilipović, Ivan, Kotur-Stevuljević, Jelena, Simić, Ljubica, Sopta, Jelena, Leposavić, Gordana, "Sex-Based Differences in Monocytic Lineage Cells Contribute to More Severe Collagen-Induced Arthritis in Female Rats Compared with Male Rats" in Inflammation, 43, no. 6 (2020):2312-2331,
https://doi.org/10.1007/s10753-020-01302-0 . .

TY  - JOUR
AU  - Bufan, Biljana
AU  - Jančić, Ivan
AU  - Stojić-Vukanić, Zorica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3642
AB  - Tumor necrosis factor (TNF)-α is a proinflammatory cytokine with a role in immunity to pathogens, as well as in the pathogenesis of several autoimmune/inflammatory diseases. Biological drugs targeting this cytokine and inhibiting its effects are designed. Until today, five TNF-α inhibitors are approved: infliximab, adalimumab, golimumab (monoclonal antibodies), certolizumab pegol (pegylated antigen-binding fragment of immunoglobulin), and etanercept [TNF receptor type 2-fragment crystallizable (Fc) of immunoglobulin fusion protein]. Their approved biosimilars are on the market, too. They are mainly used for the treatment of rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Although TNF-α inhibitors are present in clinical practice for more than two decades and are established as an efficacious therapeutics, researchers are still occupied by revealing the complex mechanisms of their action. Namely, in addition to binding and neutralisation of soluble TNF-α, these drugs also bind/block transmembrane form of TNF-α (tmTNF-α), trigger diverse intracellular signals in tmTNF-α positive cells (a process named “reverse signalling”) or, if they have an Fc fragment, mediate killing of tmTNF-α-expressing cells by other immune cells or the complement system. Also, TNF-α inhibitors that contain Fc portion of the IgG antibody may affect Fc receptor-expressing cells and have an effector function quite independent of their TNF-α neutralisation capacity.
AB  - Faktor nekroze tumora (TNF)-a je citokin koji ima značajnu ulogu u patogenezi nekih autoimunskih/inflamatornih bolesti. Shodno tome, dizajnirani su biološki lekovi koji ciljano inhibiraju efekte koje on ostvaruje posredstvom svojih receptora. Do danas je odobreno pet lekova koji inhibiraju TNF-a: infliksimab, adalimumab, golimumab (monoklonska antitela), certolizumab pegol (pegilovani antigen-vezujući fragment imunoglobulina) i etanercept [TNF receptor 2-kristalizujući fragment (Fc) imunoglobulina fuzioni protein]. Takođe, brojni biosimilari ovih lekova su odobreni za primenu. Glavne indikacije za primenu anti-TNF-a lekova su: reumatoidni artritis, inflamatorne bolesti creva, psorijaza. Iako se TNF-a inhibitori više od dve decenije uspešno koriste u kliničkoj praksi, složeni mehanizmi njihovog delovanja još uvek nisu potpuno poznati. Naime, pokazano je da se ovi lekovi, osim vezivanja i neutralizacije solubilnog TNF-a, mogu vezati i za transmembransku formu ovog citokina i blokirati je i/ili pokrenuti prenos signala u ćeliju koja ispoljava ovaj molekul ("reverzni prenos signala"). Takođe, ovi lekovi, ukoliko poseduju Fc fragment, mogu posredovati i u ubijanju ćelija koje ispoljavaju membransku formu TNF-a aktivacijom drugih ćelija imunskog sistema ili sistema komplementa ili modulisati funkciju ćelija koje ispoljavaju receptore za Fc fragmanet i ostvarivati efektorske funkcije nezavisno od njihove sposobnosti da blokiraju/neutrališu TNF-a.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Inhibitors of tumor necrosis factor-α and mechanisms of their action
T1  - Inhibitori faktora nekroze tumora–α i mehanizmi njihovog dejstva
VL  - 70
IS  - 3
SP  - 109
EP  - 129
DO  - 10.5937/arhfarm2003109B
ER  - 

@article{
author = "Bufan, Biljana and Jančić, Ivan and Stojić-Vukanić, Zorica",
year = "2020",
abstract = "Tumor necrosis factor (TNF)-α is a proinflammatory cytokine with a role in immunity to pathogens, as well as in the pathogenesis of several autoimmune/inflammatory diseases. Biological drugs targeting this cytokine and inhibiting its effects are designed. Until today, five TNF-α inhibitors are approved: infliximab, adalimumab, golimumab (monoclonal antibodies), certolizumab pegol (pegylated antigen-binding fragment of immunoglobulin), and etanercept [TNF receptor type 2-fragment crystallizable (Fc) of immunoglobulin fusion protein]. Their approved biosimilars are on the market, too. They are mainly used for the treatment of rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Although TNF-α inhibitors are present in clinical practice for more than two decades and are established as an efficacious therapeutics, researchers are still occupied by revealing the complex mechanisms of their action. Namely, in addition to binding and neutralisation of soluble TNF-α, these drugs also bind/block transmembrane form of TNF-α (tmTNF-α), trigger diverse intracellular signals in tmTNF-α positive cells (a process named “reverse signalling”) or, if they have an Fc fragment, mediate killing of tmTNF-α-expressing cells by other immune cells or the complement system. Also, TNF-α inhibitors that contain Fc portion of the IgG antibody may affect Fc receptor-expressing cells and have an effector function quite independent of their TNF-α neutralisation capacity., Faktor nekroze tumora (TNF)-a je citokin koji ima značajnu ulogu u patogenezi nekih autoimunskih/inflamatornih bolesti. Shodno tome, dizajnirani su biološki lekovi koji ciljano inhibiraju efekte koje on ostvaruje posredstvom svojih receptora. Do danas je odobreno pet lekova koji inhibiraju TNF-a: infliksimab, adalimumab, golimumab (monoklonska antitela), certolizumab pegol (pegilovani antigen-vezujući fragment imunoglobulina) i etanercept [TNF receptor 2-kristalizujući fragment (Fc) imunoglobulina fuzioni protein]. Takođe, brojni biosimilari ovih lekova su odobreni za primenu. Glavne indikacije za primenu anti-TNF-a lekova su: reumatoidni artritis, inflamatorne bolesti creva, psorijaza. Iako se TNF-a inhibitori više od dve decenije uspešno koriste u kliničkoj praksi, složeni mehanizmi njihovog delovanja još uvek nisu potpuno poznati. Naime, pokazano je da se ovi lekovi, osim vezivanja i neutralizacije solubilnog TNF-a, mogu vezati i za transmembransku formu ovog citokina i blokirati je i/ili pokrenuti prenos signala u ćeliju koja ispoljava ovaj molekul ("reverzni prenos signala"). Takođe, ovi lekovi, ukoliko poseduju Fc fragment, mogu posredovati i u ubijanju ćelija koje ispoljavaju membransku formu TNF-a aktivacijom drugih ćelija imunskog sistema ili sistema komplementa ili modulisati funkciju ćelija koje ispoljavaju receptore za Fc fragmanet i ostvarivati efektorske funkcije nezavisno od njihove sposobnosti da blokiraju/neutrališu TNF-a.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Inhibitors of tumor necrosis factor-α and mechanisms of their action, Inhibitori faktora nekroze tumora–α i mehanizmi njihovog dejstva",
volume = "70",
number = "3",
pages = "109-129",
doi = "10.5937/arhfarm2003109B"
}

Bufan, B., Jančić, I.,& Stojić-Vukanić, Z.. (2020). Inhibitors of tumor necrosis factor-α and mechanisms of their action. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 70(3), 109-129.
https://doi.org/10.5937/arhfarm2003109B

Bufan B, Jančić I, Stojić-Vukanić Z. Inhibitors of tumor necrosis factor-α and mechanisms of their action. in Arhiv za farmaciju. 2020;70(3):109-129.
doi:10.5937/arhfarm2003109B .

Bufan, Biljana, Jančić, Ivan, Stojić-Vukanić, Zorica, "Inhibitors of tumor necrosis factor-α and mechanisms of their action" in Arhiv za farmaciju, 70, no. 3 (2020):109-129,
https://doi.org/10.5937/arhfarm2003109B . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Vuković, R., Zeljković, A., Bufan, B., Spasojević-Kalimanovska, V., Milenković, T.,& Vekić, J.. (2019). Hashimoto Thyroiditis and Dyslipidemia in Childhood: A Review. in Frontiers in Endocrinology
Frontiers Media S.A.., 10.
https://doi.org/10.3389/fendo.2019.00868

Vuković R, Zeljković A, Bufan B, Spasojević-Kalimanovska V, Milenković T, Vekić J. Hashimoto Thyroiditis and Dyslipidemia in Childhood: A Review. in Frontiers in Endocrinology. 2019;10.
doi:10.3389/fendo.2019.00868 .

Vuković, Rade, Zeljković, Aleksandra, Bufan, Biljana, Spasojević-Kalimanovska, Vesna, Milenković, Tatjana, Vekić, Jelena, "Hashimoto Thyroiditis and Dyslipidemia in Childhood: A Review" in Frontiers in Endocrinology, 10 (2019),
https://doi.org/10.3389/fendo.2019.00868 . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Stojkovska, Jasmina
AU  - Đurđević, Željka
AU  - Jančić, Ivan
AU  - Bufan, Biljana
AU  - Milenković, Marina
AU  - Janković, Radmila
AU  - Mišković-Stanković, Vesna
AU  - Obradović, Bojana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3169
AB  - In the present study, possibilities for using novel nanocomposites based on alginate and silver nanoparticles for wound treatment were investigated in a second-degree thermal burn model in Wistar rats. Silver nanoparticles (AgNPs) were electrochemically synthesized in alginate solutions that were further utilized to obtain the Ag/alginate solution and microfibers for subsequent in vivo studies. Daily applications of the Ag/alginate colloid solution, containing AgNPs, alginate and ascorbic acid (G3), wet Ag/alginate microfibers containing AgNPs (G5) and dry Ag/alginate microfibers containing AgNPs (G6) were compared to treatments with a commercial cream containing silver sulfadiazine (G2) and a commercial Ca-alginate wound dressing containing silver ions (G4), as well as to the untreated controls (G1). Results of the in vivo study have shown faster healing in treated wounds, which completely healed on day 19 (G4, G5 and G6) and 21 (G2 and G3) after the thermal injury, while the period for complete reepitelization of untreated wounds (G1) was 25 days. The macroscopic analysis has shown that scabs fell off between day 10 and 12 after the thermal injury induction in treated groups, whereas between day 15 and 16 in the control group. These macroscopic findings were supported by the results of histopathological analyses, which have shown enhanced granulation and reepithelization, reduced inflammation and improved organization of the extracellular matrix in treated groups without adverse effects. Among the treated groups, dressings based on Ca-alginate (G4-G6) induced enhanced healing as compared to the other two groups (G2, G3), which could be attributed to additional stimuli of released Ca2+. The obtained results indicated potentials of novel nanocomposites based on alginate and AgNPs for therapeutic applications in wound treatments.
PB  - Sage Publications Ltd, London
T2  - Journal of Biomaterials Applications
T1  - Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments
VL  - 32
IS  - 9
SP  - 1197
EP  - 1211
DO  - 10.1177/0885328218759564
ER  - 

@article{
author = "Stojkovska, Jasmina and Đurđević, Željka and Jančić, Ivan and Bufan, Biljana and Milenković, Marina and Janković, Radmila and Mišković-Stanković, Vesna and Obradović, Bojana",
year = "2018",
abstract = "In the present study, possibilities for using novel nanocomposites based on alginate and silver nanoparticles for wound treatment were investigated in a second-degree thermal burn model in Wistar rats. Silver nanoparticles (AgNPs) were electrochemically synthesized in alginate solutions that were further utilized to obtain the Ag/alginate solution and microfibers for subsequent in vivo studies. Daily applications of the Ag/alginate colloid solution, containing AgNPs, alginate and ascorbic acid (G3), wet Ag/alginate microfibers containing AgNPs (G5) and dry Ag/alginate microfibers containing AgNPs (G6) were compared to treatments with a commercial cream containing silver sulfadiazine (G2) and a commercial Ca-alginate wound dressing containing silver ions (G4), as well as to the untreated controls (G1). Results of the in vivo study have shown faster healing in treated wounds, which completely healed on day 19 (G4, G5 and G6) and 21 (G2 and G3) after the thermal injury, while the period for complete reepitelization of untreated wounds (G1) was 25 days. The macroscopic analysis has shown that scabs fell off between day 10 and 12 after the thermal injury induction in treated groups, whereas between day 15 and 16 in the control group. These macroscopic findings were supported by the results of histopathological analyses, which have shown enhanced granulation and reepithelization, reduced inflammation and improved organization of the extracellular matrix in treated groups without adverse effects. Among the treated groups, dressings based on Ca-alginate (G4-G6) induced enhanced healing as compared to the other two groups (G2, G3), which could be attributed to additional stimuli of released Ca2+. The obtained results indicated potentials of novel nanocomposites based on alginate and AgNPs for therapeutic applications in wound treatments.",
publisher = "Sage Publications Ltd, London",
journal = "Journal of Biomaterials Applications",
title = "Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments",
volume = "32",
number = "9",
pages = "1197-1211",
doi = "10.1177/0885328218759564"
}

Stojkovska, J., Đurđević, Ž., Jančić, I., Bufan, B., Milenković, M., Janković, R., Mišković-Stanković, V.,& Obradović, B.. (2018). Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments. in Journal of Biomaterials Applications
Sage Publications Ltd, London., 32(9), 1197-1211.
https://doi.org/10.1177/0885328218759564

Stojkovska J, Đurđević Ž, Jančić I, Bufan B, Milenković M, Janković R, Mišković-Stanković V, Obradović B. Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments. in Journal of Biomaterials Applications. 2018;32(9):1197-1211.
doi:10.1177/0885328218759564 .

Stojkovska, Jasmina, Đurđević, Željka, Jančić, Ivan, Bufan, Biljana, Milenković, Marina, Janković, Radmila, Mišković-Stanković, Vesna, Obradović, Bojana, "Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments" in Journal of Biomaterials Applications, 32, no. 9 (2018):1197-1211,
https://doi.org/10.1177/0885328218759564 . .

TY  - JOUR
AU  - Nacka-Aleksić, Mirjana
AU  - Stojanović, Marija
AU  - Simić, Lidija
AU  - Bufan, Biljana
AU  - Kotur-Stevuljević, Jelena
AU  - Stojić-Vukanić, Zorica
AU  - Dimitrijević, Mirjana
AU  - Ražić, Slavica
AU  - Leposavić, Gordana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2795
AB  - To close the gap in our knowledge of sex influence on age-related changes in inflammation-oxidation state in spinal cord (SC) relevant to inflammation/oxidative-stress associated neuropathologies, 2-3 month-old (young) and 18-20 month-old (old) rats, exhibiting increased level of IL-6, a commonly used marker of inflamm-aging, were examined for inflammatory/redox status, and the underlying regulatory networks' molecules expression. With age, rat SC microglia became sensitized ("primed"), while SC tissue shifted towards mild inflammatory state, with increased levels of proinflammatory IL-1 beta (key marker of microglial systemic inflammation-induced neurotoxicity), which was more prominent in males. This, most likely, reflected age- and sex-related impairment in the expression of CX3CR1, the receptor for fractalkine (CX3CL1), the soluble factor which regulates microglial activation and diminishes production of IL-1 beta (central for fractalkine neuroprotection). Considering that (i) age-related changes in SC IL-1 beta expression were not followed by complementary changes in SC IL-6 expression, and (ii) the reversal in the direction of the sex bias in circulating IL-6 level and SC IL-1 beta expression, it seems obvious that there are tissue-specific differences in the proinflammatory cytokine profile. Additionally, old male rat SC exhibited greater oxidative damage than female, reflecting, most likely, their lower capacity to maintain the pro-oxidant-antioxidant balance. In conclusion, these findings, apart from highlighting the significance of sex for age-associated changes in SC inflammation-oxidation, may be relevant for understating sex differences in human inflammation/oxidative-stress related SC diseases, and consequently, for optimizing their prevention/therapy.
PB  - Springer, New York
T2  - Biogerontology
T1  - Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state
VL  - 18
IS  - 5
SP  - 821
EP  - 839
DO  - 10.1007/s10522-017-9726-4
ER  - 

@article{
author = "Nacka-Aleksić, Mirjana and Stojanović, Marija and Simić, Lidija and Bufan, Biljana and Kotur-Stevuljević, Jelena and Stojić-Vukanić, Zorica and Dimitrijević, Mirjana and Ražić, Slavica and Leposavić, Gordana",
year = "2017",
abstract = "To close the gap in our knowledge of sex influence on age-related changes in inflammation-oxidation state in spinal cord (SC) relevant to inflammation/oxidative-stress associated neuropathologies, 2-3 month-old (young) and 18-20 month-old (old) rats, exhibiting increased level of IL-6, a commonly used marker of inflamm-aging, were examined for inflammatory/redox status, and the underlying regulatory networks' molecules expression. With age, rat SC microglia became sensitized ("primed"), while SC tissue shifted towards mild inflammatory state, with increased levels of proinflammatory IL-1 beta (key marker of microglial systemic inflammation-induced neurotoxicity), which was more prominent in males. This, most likely, reflected age- and sex-related impairment in the expression of CX3CR1, the receptor for fractalkine (CX3CL1), the soluble factor which regulates microglial activation and diminishes production of IL-1 beta (central for fractalkine neuroprotection). Considering that (i) age-related changes in SC IL-1 beta expression were not followed by complementary changes in SC IL-6 expression, and (ii) the reversal in the direction of the sex bias in circulating IL-6 level and SC IL-1 beta expression, it seems obvious that there are tissue-specific differences in the proinflammatory cytokine profile. Additionally, old male rat SC exhibited greater oxidative damage than female, reflecting, most likely, their lower capacity to maintain the pro-oxidant-antioxidant balance. In conclusion, these findings, apart from highlighting the significance of sex for age-associated changes in SC inflammation-oxidation, may be relevant for understating sex differences in human inflammation/oxidative-stress related SC diseases, and consequently, for optimizing their prevention/therapy.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state",
volume = "18",
number = "5",
pages = "821-839",
doi = "10.1007/s10522-017-9726-4"
}

Nacka-Aleksić, M., Stojanović, M., Simić, L., Bufan, B., Kotur-Stevuljević, J., Stojić-Vukanić, Z., Dimitrijević, M., Ražić, S.,& Leposavić, G.. (2017). Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state. in Biogerontology
Springer, New York., 18(5), 821-839.
https://doi.org/10.1007/s10522-017-9726-4

Nacka-Aleksić M, Stojanović M, Simić L, Bufan B, Kotur-Stevuljević J, Stojić-Vukanić Z, Dimitrijević M, Ražić S, Leposavić G. Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state. in Biogerontology. 2017;18(5):821-839.
doi:10.1007/s10522-017-9726-4 .

Nacka-Aleksić, Mirjana, Stojanović, Marija, Simić, Lidija, Bufan, Biljana, Kotur-Stevuljević, Jelena, Stojić-Vukanić, Zorica, Dimitrijević, Mirjana, Ražić, Slavica, Leposavić, Gordana, "Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state" in Biogerontology, 18, no. 5 (2017):821-839,
https://doi.org/10.1007/s10522-017-9726-4 . .