Nikolić, Milan

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Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood

Jakovljević, Danijel; Nikolić, Milan; Jovanović, Vesna; Vidonja Uzelac, Teodora; Nikolić-Kokić, Aleksandra; Novaković, Emilija; Miljević, Čedo; Milovanovć, Maja; Blagojević, Duško

(Basel: MDPI, 2024)

TY  - JOUR
AU  - Jakovljević, Danijel
AU  - Nikolić, Milan
AU  - Jovanović, Vesna
AU  - Vidonja Uzelac, Teodora
AU  - Nikolić-Kokić, Aleksandra
AU  - Novaković, Emilija
AU  - Miljević, Čedo
AU  - Milovanovć, Maja
AU  - Blagojević, Duško
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6510
AB  - Background: Epilepsy is a chronic brain disease affecting millions of people worldwide,
but little is known about the impact of anti-seizure medications on redox homeostasis. Methods:
This study aimed to compare the effects of the long-term use of oral anti-seizure medications in
monotherapy (lamotrigine, carbamazepine, and valproate) on antioxidant enzymes: superoxide dismutase,
catalase, glutathione peroxidase, glutathione reductase, haemoglobin, and methaemoglobin
content in erythrocytes, and concentrations of total proteins and thiols, nitrites, lipid peroxides and
total glutathione in the plasma of epilepsy patients and drug-naïve patients. Results: The results
showed that lamotrigine therapy led to lower superoxide dismutase activity (p < 0.005) and lower
concentrations of total thiols (p < 0.01) and lipid peroxides (p < 0.01) compared to controls. On the
other hand, therapy with carbamazepine increased nitrite levels (p < 0.01) but reduced superoxide
dismutase activity (p < 0.005). In the valproate group, only a decrease in catalase activity was observed
(p < 0.005). Canonical discriminant analysis showed that the composition of antioxidant enzymes in
erythrocytes was different for both the lamotrigine and carbamazepine groups, while the controls
were separated from all others. Conclusions: Monotherapy with anti-seizure medications discretely
alters redox homeostasis, followed by distinct relationships between antioxidant components.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood
IS  - 1
VL  - 17
DO  - 10.3390/ph17010130
SP  - 130
ER  - 
@article{
author = "Jakovljević, Danijel and Nikolić, Milan and Jovanović, Vesna and Vidonja Uzelac, Teodora and Nikolić-Kokić, Aleksandra and Novaković, Emilija and Miljević, Čedo and Milovanovć, Maja and Blagojević, Duško",
year = "2024",
abstract = "Background: Epilepsy is a chronic brain disease affecting millions of people worldwide,
but little is known about the impact of anti-seizure medications on redox homeostasis. Methods:
This study aimed to compare the effects of the long-term use of oral anti-seizure medications in
monotherapy (lamotrigine, carbamazepine, and valproate) on antioxidant enzymes: superoxide dismutase,
catalase, glutathione peroxidase, glutathione reductase, haemoglobin, and methaemoglobin
content in erythrocytes, and concentrations of total proteins and thiols, nitrites, lipid peroxides and
total glutathione in the plasma of epilepsy patients and drug-naïve patients. Results: The results
showed that lamotrigine therapy led to lower superoxide dismutase activity (p < 0.005) and lower
concentrations of total thiols (p < 0.01) and lipid peroxides (p < 0.01) compared to controls. On the
other hand, therapy with carbamazepine increased nitrite levels (p < 0.01) but reduced superoxide
dismutase activity (p < 0.005). In the valproate group, only a decrease in catalase activity was observed
(p < 0.005). Canonical discriminant analysis showed that the composition of antioxidant enzymes in
erythrocytes was different for both the lamotrigine and carbamazepine groups, while the controls
were separated from all others. Conclusions: Monotherapy with anti-seizure medications discretely
alters redox homeostasis, followed by distinct relationships between antioxidant components.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood",
number = "1",
volume = "17",
doi = "10.3390/ph17010130",
pages = "130"
}
Jakovljević, D., Nikolić, M., Jovanović, V., Vidonja Uzelac, T., Nikolić-Kokić, A., Novaković, E., Miljević, Č., Milovanovć, M.,& Blagojević, D.. (2024). Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood. in Pharmaceuticals
Basel: MDPI., 17(1), 130.
https://doi.org/10.3390/ph17010130
Jakovljević D, Nikolić M, Jovanović V, Vidonja Uzelac T, Nikolić-Kokić A, Novaković E, Miljević Č, Milovanovć M, Blagojević D. Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood. in Pharmaceuticals. 2024;17(1):130.
doi:10.3390/ph17010130 .
Jakovljević, Danijel, Nikolić, Milan, Jovanović, Vesna, Vidonja Uzelac, Teodora, Nikolić-Kokić, Aleksandra, Novaković, Emilija, Miljević, Čedo, Milovanovć, Maja, Blagojević, Duško, "Influence of Long-Term Anti-Seizure Medications on Redox Parameters in Human Blood" in Pharmaceuticals, 17, no. 1 (2024):130,
https://doi.org/10.3390/ph17010130 . .
1

Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity

Vukčević, Marija; Šerović, Katarina; Despot, Mateja; Nikolić-Kokić, Aleksandra; Vujović, Aleksandra; Nikolić, Milan; Blagojević, Duško; Jovanović, Tanja; Despot, Dragana

(Basel: MDPI, 2024)

TY  - JOUR
AU  - Vukčević, Marija
AU  - Šerović, Katarina
AU  - Despot, Mateja
AU  - Nikolić-Kokić, Aleksandra
AU  - Vujović, Aleksandra
AU  - Nikolić, Milan
AU  - Blagojević, Duško
AU  - Jovanović, Tanja
AU  - Despot, Dragana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6495
AB  - Background: Several vaccines against COVID-19 have been developed and licensed to
enhance the immune response against SARS-CoV-2. Similarly, previous infection with SARS-CoV-
2 has been shown to provide significant protection against severe infection and hospitalization.
Methods: We investigated the effect of three doses of the Sinopharm vaccine and SARS-CoV-2
infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-
S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies, and INF γ. Results: Our results showed
that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while
endocrinological diseases decreased the level of neutralizing antibodies and anti-N IgG antibodies,
suggesting that these diseases alter the effect of vaccine-induced immunity. In addition, there was a
significant decrease in anti-S1 IgG levels at 6 months and in anti-N IgG levels 18 months post-infection,
while neutralizing antibodies and INF γ levels were constant at 3, 6, and 18 months post-infection.
Conclusions: Our results confirm the emergence of hybrid immunity, which is the strongest and
most durable compared to natural immunity or vaccine-induced immunity. Significant positive
correlations were found between humoral and cellular immunity markers: neutralizing antibodies,
anti-S1 IgG and anti-N IgG antibodies, and INF γ, indicating a unique coordinated response specific
to COVID-19.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity
IS  - 1
VL  - 17
DO  - 10.3390/ph17010122
SP  - 122
ER  - 
@article{
author = "Vukčević, Marija and Šerović, Katarina and Despot, Mateja and Nikolić-Kokić, Aleksandra and Vujović, Aleksandra and Nikolić, Milan and Blagojević, Duško and Jovanović, Tanja and Despot, Dragana",
year = "2024",
abstract = "Background: Several vaccines against COVID-19 have been developed and licensed to
enhance the immune response against SARS-CoV-2. Similarly, previous infection with SARS-CoV-
2 has been shown to provide significant protection against severe infection and hospitalization.
Methods: We investigated the effect of three doses of the Sinopharm vaccine and SARS-CoV-2
infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-
S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies, and INF γ. Results: Our results showed
that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while
endocrinological diseases decreased the level of neutralizing antibodies and anti-N IgG antibodies,
suggesting that these diseases alter the effect of vaccine-induced immunity. In addition, there was a
significant decrease in anti-S1 IgG levels at 6 months and in anti-N IgG levels 18 months post-infection,
while neutralizing antibodies and INF γ levels were constant at 3, 6, and 18 months post-infection.
Conclusions: Our results confirm the emergence of hybrid immunity, which is the strongest and
most durable compared to natural immunity or vaccine-induced immunity. Significant positive
correlations were found between humoral and cellular immunity markers: neutralizing antibodies,
anti-S1 IgG and anti-N IgG antibodies, and INF γ, indicating a unique coordinated response specific
to COVID-19.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity",
number = "1",
volume = "17",
doi = "10.3390/ph17010122",
pages = "122"
}
Vukčević, M., Šerović, K., Despot, M., Nikolić-Kokić, A., Vujović, A., Nikolić, M., Blagojević, D., Jovanović, T.,& Despot, D.. (2024). Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity. in Pharmaceuticals
Basel: MDPI., 17(1), 122.
https://doi.org/10.3390/ph17010122
Vukčević M, Šerović K, Despot M, Nikolić-Kokić A, Vujović A, Nikolić M, Blagojević D, Jovanović T, Despot D. Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity. in Pharmaceuticals. 2024;17(1):122.
doi:10.3390/ph17010122 .
Vukčević, Marija, Šerović, Katarina, Despot, Mateja, Nikolić-Kokić, Aleksandra, Vujović, Aleksandra, Nikolić, Milan, Blagojević, Duško, Jovanović, Tanja, Despot, Dragana, "Humoral and Cellular Immune Response after Three Doses of Sinopharm [Vero Cell]-Inactivated COVID-19 Vaccine in Combination with SARS-CoV-2 Infection Leads to Hybrid Immunity" in Pharmaceuticals, 17, no. 1 (2024):122,
https://doi.org/10.3390/ph17010122 . .

Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?

Platanić-Arizanović, Lena; Gligorijević, Nikola; Cvijetić, Ilija; Mijatović, Aleksandar; Krstić-Ristivojević, Maja; Minić, Simeon; Nikolić-Kokić, Aleksandra; Miljević, Čedo; Nikolić, Milan

(Basel: MDPI, 2023)

TY  - JOUR
AU  - Platanić-Arizanović, Lena
AU  - Gligorijević, Nikola
AU  - Cvijetić, Ilija
AU  - Mijatović, Aleksandar
AU  - Krstić-Ristivojević, Maja
AU  - Minić, Simeon
AU  - Nikolić-Kokić, Aleksandra
AU  - Miljević, Čedo
AU  - Nikolić, Milan
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6028
AB  - : Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes
are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human
hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching
at different temperatures and data obtained from the van’t Hoff diagram and molecular docking
indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site
for all drugs in the central cavity near αβ interfaces and is dominantly mediated through hydrophobic
forces. The association constants were lower-moderate strength (~104 M−1
), the highest observed
for clozapine (2.2 × 104 M−1 at 25 ◦C). The clozapine binding showed “friendly” effects: increased
α-helical content, a higher melting point, and protein protection from free radical-mediated oxidation.
On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing
ferrihemoglobin content, a possible “foe”. Since the interaction of proteins with drugs plays a vital
role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the
obtained findings is briefly discussed.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?
IS  - 10
VL  - 24
DO  - 10.3390/ijms24108921
SP  - 8921
ER  - 
@article{
author = "Platanić-Arizanović, Lena and Gligorijević, Nikola and Cvijetić, Ilija and Mijatović, Aleksandar and Krstić-Ristivojević, Maja and Minić, Simeon and Nikolić-Kokić, Aleksandra and Miljević, Čedo and Nikolić, Milan",
year = "2023",
abstract = ": Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes
are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human
hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching
at different temperatures and data obtained from the van’t Hoff diagram and molecular docking
indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site
for all drugs in the central cavity near αβ interfaces and is dominantly mediated through hydrophobic
forces. The association constants were lower-moderate strength (~104 M−1
), the highest observed
for clozapine (2.2 × 104 M−1 at 25 ◦C). The clozapine binding showed “friendly” effects: increased
α-helical content, a higher melting point, and protein protection from free radical-mediated oxidation.
On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing
ferrihemoglobin content, a possible “foe”. Since the interaction of proteins with drugs plays a vital
role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the
obtained findings is briefly discussed.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?",
number = "10",
volume = "24",
doi = "10.3390/ijms24108921",
pages = "8921"
}
Platanić-Arizanović, L., Gligorijević, N., Cvijetić, I., Mijatović, A., Krstić-Ristivojević, M., Minić, S., Nikolić-Kokić, A., Miljević, Č.,& Nikolić, M.. (2023). Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?. in International Journal of Molecular Sciences
Basel: MDPI., 24(10), 8921.
https://doi.org/10.3390/ijms24108921
Platanić-Arizanović L, Gligorijević N, Cvijetić I, Mijatović A, Krstić-Ristivojević M, Minić S, Nikolić-Kokić A, Miljević Č, Nikolić M. Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?. in International Journal of Molecular Sciences. 2023;24(10):8921.
doi:10.3390/ijms24108921 .
Platanić-Arizanović, Lena, Gligorijević, Nikola, Cvijetić, Ilija, Mijatović, Aleksandar, Krstić-Ristivojević, Maja, Minić, Simeon, Nikolić-Kokić, Aleksandra, Miljević, Čedo, Nikolić, Milan, "Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes?" in International Journal of Molecular Sciences, 24, no. 10 (2023):8921,
https://doi.org/10.3390/ijms24108921 . .
2
2

Effect of atypical antipsychotics on antioxidant enzyme activities in human erythrocytes (in vitro study)

Miljević, Čedo; Nikolić-Kokić, Aleksandra; Nikolić, Milan; Niketić, Vesna; Spasić, Mihajlo; Lečić-Toševski, Dušica; Blagojević, Duško

(John Wiley & Sons, Ltd., 2013)

TY  - JOUR
AU  - Miljević, Čedo
AU  - Nikolić-Kokić, Aleksandra
AU  - Nikolić, Milan
AU  - Niketić, Vesna
AU  - Spasić, Mihajlo
AU  - Lečić-Toševski, Dušica
AU  - Blagojević, Duško
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6359
AB  - Objective This study was set out to examine the impact of atypical antipsychotic drugs: aripiprazole, clozapine, ziprasidone, olanzapine, quetiapine, sertindole and amisulpride on the activity of antioxidant defence enzymes in human erythrocytes in vitro. Methods Cu,Zn-superoxide dismutase (SOD1), catalase (CAT), selenium-dependent glutathione peroxidase and glutathione reductase activities were determined after drugs incubation with blood of 15 apparently healthy non-smoking male volunteers (ages 23–39) for 1 h at 37  C. Results A statistically significant increase in SOD1 activity was found in samples incubated with aripiprazole (p<0.01) and quetiapine (p<0.05) compared with incubated control. SOD1 activity profile following native polyacrylamide gel electrophoresis indicates that aripiprazole and quetiapine protect enzyme activity from inhibition with hydrogen peroxide. Our results showed that sertindole decreases activity of CAT comparing with control non-treated erythrocytes. Moreover, in sertindole treated erythrocytes, negative correlation between SOD1 and glutathione peroxidase activities was found. Increased amount of hydrogen peroxide in such situation may leave erythrocytes and transform their role in circulation from anti-oxidative to pro-oxidative. Conclusions Our results indicate that mechanism through sertindole could express its in vivo toxic effects and point toward possible (neuro) protective effects of aripiprazole and quetiapine.
PB  - John Wiley & Sons, Ltd.
T2  - Human Psychopharmacology: Clinical and Experimental
T1  - Effect of atypical antipsychotics on antioxidant enzyme activities in human erythrocytes (in vitro study)
IS  - 1
VL  - 28
DO  - 10.1002/hup.2272
SP  - 1
EP  - 6
ER  - 
@article{
author = "Miljević, Čedo and Nikolić-Kokić, Aleksandra and Nikolić, Milan and Niketić, Vesna and Spasić, Mihajlo and Lečić-Toševski, Dušica and Blagojević, Duško",
year = "2013",
abstract = "Objective This study was set out to examine the impact of atypical antipsychotic drugs: aripiprazole, clozapine, ziprasidone, olanzapine, quetiapine, sertindole and amisulpride on the activity of antioxidant defence enzymes in human erythrocytes in vitro. Methods Cu,Zn-superoxide dismutase (SOD1), catalase (CAT), selenium-dependent glutathione peroxidase and glutathione reductase activities were determined after drugs incubation with blood of 15 apparently healthy non-smoking male volunteers (ages 23–39) for 1 h at 37  C. Results A statistically significant increase in SOD1 activity was found in samples incubated with aripiprazole (p<0.01) and quetiapine (p<0.05) compared with incubated control. SOD1 activity profile following native polyacrylamide gel electrophoresis indicates that aripiprazole and quetiapine protect enzyme activity from inhibition with hydrogen peroxide. Our results showed that sertindole decreases activity of CAT comparing with control non-treated erythrocytes. Moreover, in sertindole treated erythrocytes, negative correlation between SOD1 and glutathione peroxidase activities was found. Increased amount of hydrogen peroxide in such situation may leave erythrocytes and transform their role in circulation from anti-oxidative to pro-oxidative. Conclusions Our results indicate that mechanism through sertindole could express its in vivo toxic effects and point toward possible (neuro) protective effects of aripiprazole and quetiapine.",
publisher = "John Wiley & Sons, Ltd.",
journal = "Human Psychopharmacology: Clinical and Experimental",
title = "Effect of atypical antipsychotics on antioxidant enzyme activities in human erythrocytes (in vitro study)",
number = "1",
volume = "28",
doi = "10.1002/hup.2272",
pages = "1-6"
}
Miljević, Č., Nikolić-Kokić, A., Nikolić, M., Niketić, V., Spasić, M., Lečić-Toševski, D.,& Blagojević, D.. (2013). Effect of atypical antipsychotics on antioxidant enzyme activities in human erythrocytes (in vitro study). in Human Psychopharmacology: Clinical and Experimental
John Wiley & Sons, Ltd.., 28(1), 1-6.
https://doi.org/10.1002/hup.2272
Miljević Č, Nikolić-Kokić A, Nikolić M, Niketić V, Spasić M, Lečić-Toševski D, Blagojević D. Effect of atypical antipsychotics on antioxidant enzyme activities in human erythrocytes (in vitro study). in Human Psychopharmacology: Clinical and Experimental. 2013;28(1):1-6.
doi:10.1002/hup.2272 .
Miljević, Čedo, Nikolić-Kokić, Aleksandra, Nikolić, Milan, Niketić, Vesna, Spasić, Mihajlo, Lečić-Toševski, Dušica, Blagojević, Duško, "Effect of atypical antipsychotics on antioxidant enzyme activities in human erythrocytes (in vitro study)" in Human Psychopharmacology: Clinical and Experimental, 28, no. 1 (2013):1-6,
https://doi.org/10.1002/hup.2272 . .
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