TY  - CONF
AU  - Đikić, Teodora
AU  - Martí, Yasmina
AU  - Spyrakis, Francesca
AU  - Lau, Thorsten
AU  - Benedetti, Paolo
AU  - Davey, Gavin
AU  - Schloss, Patrick
AU  - Yelekci, Kemal
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4887
AB  - Abnormally folded alpha-synuclein protein, dysfunctional mitochondria, increased oxidative stress and reduced dopamine
neurotransmitter synthesis are a
ll extremely well characterized phenomena in Parkinson’s disease (PD) and are thought to be interconnected. While direct
targeting of these areas has demonstrated neuroprotection in vitro and in vivo, there has been a major lack of success in clinical
trials. A critical component in the failure of these clinical trials is the inability to specifically target drugs to dopamine producing
neurons in the brain.
New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could
represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of
extracellular dopamine, thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert
neuroprotective response because of their accumulation in the cytoplasm, are required.
By means of homology modeling, molecular docking and molecular dynamics simulations, we have generated 3D structure
models of hDAT in complex with substrate and inhibitors. Our results clearly reveal differences in binding kinetics of these
compounds to the hDAT in the open and closed conformations, critical for future drug design. The established in silico
approach allowed the identification of three promising substrate compounds that were subsequently analyzed for their
efficiency in inhibiting hDAT-dependent fluorescent substrate uptake, through in vitro live cell imaging experiments. Taken
together, our work presents the first implementation of a combined in silico/in vitro-approach enabling the selection of
promising dopaminergic neuron specific substrates.
PB  - Centar za eksperimentalnu i primenjenu fiziologiju Farmaceutskog fakulteta Univerziteta u Beogradu
C3  - 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.
T1  - In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease
SP  - 13
EP  - 14
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4887
ER  - 

@conference{
author = "Đikić, Teodora and Martí, Yasmina and Spyrakis, Francesca and Lau, Thorsten and Benedetti, Paolo and Davey, Gavin and Schloss, Patrick and Yelekci, Kemal",
year = "2019",
abstract = "Abnormally folded alpha-synuclein protein, dysfunctional mitochondria, increased oxidative stress and reduced dopamine
neurotransmitter synthesis are a
ll extremely well characterized phenomena in Parkinson’s disease (PD) and are thought to be interconnected. While direct
targeting of these areas has demonstrated neuroprotection in vitro and in vivo, there has been a major lack of success in clinical
trials. A critical component in the failure of these clinical trials is the inability to specifically target drugs to dopamine producing
neurons in the brain.
New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could
represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of
extracellular dopamine, thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert
neuroprotective response because of their accumulation in the cytoplasm, are required.
By means of homology modeling, molecular docking and molecular dynamics simulations, we have generated 3D structure
models of hDAT in complex with substrate and inhibitors. Our results clearly reveal differences in binding kinetics of these
compounds to the hDAT in the open and closed conformations, critical for future drug design. The established in silico
approach allowed the identification of three promising substrate compounds that were subsequently analyzed for their
efficiency in inhibiting hDAT-dependent fluorescent substrate uptake, through in vitro live cell imaging experiments. Taken
together, our work presents the first implementation of a combined in silico/in vitro-approach enabling the selection of
promising dopaminergic neuron specific substrates.",
publisher = "Centar za eksperimentalnu i primenjenu fiziologiju Farmaceutskog fakulteta Univerziteta u Beogradu",
journal = "2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.",
title = "In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease",
pages = "13-14",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4887"
}

Đikić, T., Martí, Y., Spyrakis, F., Lau, T., Benedetti, P., Davey, G., Schloss, P.,& Yelekci, K.. (2019). In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease. in 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.
Centar za eksperimentalnu i primenjenu fiziologiju Farmaceutskog fakulteta Univerziteta u Beogradu., 13-14.
https://hdl.handle.net/21.15107/rcub_farfar_4887

Đikić T, Martí Y, Spyrakis F, Lau T, Benedetti P, Davey G, Schloss P, Yelekci K. In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease. in 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019.. 2019;:13-14.
https://hdl.handle.net/21.15107/rcub_farfar_4887 .

Đikić, Teodora, Martí, Yasmina, Spyrakis, Francesca, Lau, Thorsten, Benedetti, Paolo, Davey, Gavin, Schloss, Patrick, Yelekci, Kemal, "In silico reconstruction of human dopamine transporter and design of novel neuroprotective drugs for Parkinson’s disease" in 2. Simpozijum iz biomedicine: bazična i klinička Neuronauka, KNJIGA SAŽETAKA, Farmaceutski fakultet - Univerzitet u Beogradu, 9. maj 2019. (2019):13-14,
https://hdl.handle.net/21.15107/rcub_farfar_4887 .

TY  - JOUR
AU  - Anđelković, Marija
AU  - Baralić, Ivana
AU  - Đorđević, Brižita
AU  - Kotur-Stevuljević, Jelena
AU  - Radivojević, Nenad
AU  - Dikić, Nenad
AU  - Radojević-Skodrić, Sanja
AU  - Stojković, Mirjana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2310
AB  - Background: The purpose of the present study was to report and discuss the hematological and biochemical behavior of elite soccer players, in order to get more insight in the physiological characteristics of these sportsmen and to provide trainers and sports doctors with useful indicators. Methods: Nineteen male soccer players volunteered to participate in this study. We followed the young elite soccer players during a competitive half season. Venous blood samples were collected between 9:00 and 10:00 a.m. after an overnight fast (10 h) at baseline, after 45 and 90 days and hematological and biochemical parameters were measured. Results: Hemoglobin and hematocrit levels were significantly reduced over the observational period (p lt 0.05), but erythrocyte count and iron levels remained unchanged. Bilirubin and ferritin levels significantly increased in response to regular soccer training (p lt 0.05). We observed a significant decrease in muscle enzyme plasma activity during the 90 days study period. ANOVA analysis revealed a significant increase in the leukocyte and neutrophil counts (p lt 0.05), in parallel with a significant decrease in the lymphocyte count (p lt 0.05) after the observational period of 90 days. Conclusions: Elite soccer players are characterized by significant changes in biochemical and hematological parameters over the half season, which are linked to training workload, as well as adaptation induced by the soccer training. Although the values of the measured parameters fell within the reference range, regular monitoring of the biochemical and hematological parameters is fundamental for the identification of a healthy status and related optimal performances by sport doctors and trainers and selection of a correct workload by trainers.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Hematological and Biochemical Parameters in Elite Soccer Players during A Competitive Half Season
VL  - 34
IS  - 4
SP  - 460
EP  - 466
DO  - 10.2478/jomb-2014-0057
ER  - 

@article{
author = "Anđelković, Marija and Baralić, Ivana and Đorđević, Brižita and Kotur-Stevuljević, Jelena and Radivojević, Nenad and Dikić, Nenad and Radojević-Skodrić, Sanja and Stojković, Mirjana",
year = "2015",
abstract = "Background: The purpose of the present study was to report and discuss the hematological and biochemical behavior of elite soccer players, in order to get more insight in the physiological characteristics of these sportsmen and to provide trainers and sports doctors with useful indicators. Methods: Nineteen male soccer players volunteered to participate in this study. We followed the young elite soccer players during a competitive half season. Venous blood samples were collected between 9:00 and 10:00 a.m. after an overnight fast (10 h) at baseline, after 45 and 90 days and hematological and biochemical parameters were measured. Results: Hemoglobin and hematocrit levels were significantly reduced over the observational period (p lt 0.05), but erythrocyte count and iron levels remained unchanged. Bilirubin and ferritin levels significantly increased in response to regular soccer training (p lt 0.05). We observed a significant decrease in muscle enzyme plasma activity during the 90 days study period. ANOVA analysis revealed a significant increase in the leukocyte and neutrophil counts (p lt 0.05), in parallel with a significant decrease in the lymphocyte count (p lt 0.05) after the observational period of 90 days. Conclusions: Elite soccer players are characterized by significant changes in biochemical and hematological parameters over the half season, which are linked to training workload, as well as adaptation induced by the soccer training. Although the values of the measured parameters fell within the reference range, regular monitoring of the biochemical and hematological parameters is fundamental for the identification of a healthy status and related optimal performances by sport doctors and trainers and selection of a correct workload by trainers.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Hematological and Biochemical Parameters in Elite Soccer Players during A Competitive Half Season",
volume = "34",
number = "4",
pages = "460-466",
doi = "10.2478/jomb-2014-0057"
}

Anđelković, M., Baralić, I., Đorđević, B., Kotur-Stevuljević, J., Radivojević, N., Dikić, N., Radojević-Skodrić, S.,& Stojković, M.. (2015). Hematological and Biochemical Parameters in Elite Soccer Players during A Competitive Half Season. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 34(4), 460-466.
https://doi.org/10.2478/jomb-2014-0057

Anđelković M, Baralić I, Đorđević B, Kotur-Stevuljević J, Radivojević N, Dikić N, Radojević-Skodrić S, Stojković M. Hematological and Biochemical Parameters in Elite Soccer Players during A Competitive Half Season. in Journal of Medical Biochemistry. 2015;34(4):460-466.
doi:10.2478/jomb-2014-0057 .

Anđelković, Marija, Baralić, Ivana, Đorđević, Brižita, Kotur-Stevuljević, Jelena, Radivojević, Nenad, Dikić, Nenad, Radojević-Skodrić, Sanja, Stojković, Mirjana, "Hematological and Biochemical Parameters in Elite Soccer Players during A Competitive Half Season" in Journal of Medical Biochemistry, 34, no. 4 (2015):460-466,
https://doi.org/10.2478/jomb-2014-0057 . .

TY  - JOUR
AU  - Đorđević, Brižita
AU  - Baralić, Ivana
AU  - Kotur-Stevuljević, Jelena
AU  - Stefanović, Aleksandra
AU  - Ivanišević, Jasmina
AU  - Radivojević, Nenad
AU  - Anđelković, Marija
AU  - Dikić, Nenad
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1654
AB  - Aim. The purpose of the current study was to examine the effect of Astaxanthin (Asx) supplementation on muscle enzymes as indirect markers of muscle damage, oxidative stress markers and antioxidant response in elite young soccer players. Methods. Thirty-two male elite soccer players were randomly assigned in a double-blind fashion to Asx and placebo (P) group. After the 90 days of supplementation, the athletes performed a 2 hour acute exercise bout. Blood samples were obtained before and after 90 days of supplementation and after the exercise at the end of observational period for analysis of thiobarbituric acid-reacting substances (TBARS), advanced oxidation protein products (AOPP), superoxide anion (O-2(center dot-)), total antioxidative status (TAS), sulphydril groups (SH), superoxide-dismutase (SOD), serum creatine kinase (CK) and aspartate aminotransferase (AST). Results. TBARS and AOPP levels did not change throughout the study. Regular training significantly increased O-2(center dot-) levels (main training effect, P lt 0.01). O-2(center dot-) increased after the soccer exercise (main exercise effect, P lt 0.01), but these changes reached statistical significance only in the P group (exercise x supplementation effect, P lt 0.05). TAS levels decreased significantly post- exercise only in P group (P lt 0.01). Both Asx and P groups experienced increase in total SH groups content (by 21% and 9%, respectively) and supplementation effect was marginally significant (P=0.08). Basal SOD activity significantly decreased both in P and in Asx group by the end of the study (main training effect, P lt 0.01). All participants showed a significant decrease in basal CK and AST activities after 90 days (main training effect, P lt 0.01 and P lt 0.001, respectively). CK and AST activities in serum significantly increased as result of soccer exercise (main exercise effect, P lt 0.001 and P lt 0.01, respectively). Postexercise CK and AST levels were significantly lower in Asx group compared to P group (P lt 0.05) Conclusion. The results of the present study suggest that soccer training and soccer exercise are associated with excessive production of free radicals and oxidative stress, which might diminish antioxidant system efficiency. Supplementation with Asx could prevent exercise induced free radical production and depletion of non-enzymatic antioxidant defense in young soccer players
PB  - Edizioni Minerva Medica, Turin
T2  - Journal of Sports Medicine and Physical Fitness
T1  - Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players
VL  - 52
IS  - 4
SP  - 382
EP  - 392
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1654
ER  - 

@article{
author = "Đorđević, Brižita and Baralić, Ivana and Kotur-Stevuljević, Jelena and Stefanović, Aleksandra and Ivanišević, Jasmina and Radivojević, Nenad and Anđelković, Marija and Dikić, Nenad",
year = "2012",
abstract = "Aim. The purpose of the current study was to examine the effect of Astaxanthin (Asx) supplementation on muscle enzymes as indirect markers of muscle damage, oxidative stress markers and antioxidant response in elite young soccer players. Methods. Thirty-two male elite soccer players were randomly assigned in a double-blind fashion to Asx and placebo (P) group. After the 90 days of supplementation, the athletes performed a 2 hour acute exercise bout. Blood samples were obtained before and after 90 days of supplementation and after the exercise at the end of observational period for analysis of thiobarbituric acid-reacting substances (TBARS), advanced oxidation protein products (AOPP), superoxide anion (O-2(center dot-)), total antioxidative status (TAS), sulphydril groups (SH), superoxide-dismutase (SOD), serum creatine kinase (CK) and aspartate aminotransferase (AST). Results. TBARS and AOPP levels did not change throughout the study. Regular training significantly increased O-2(center dot-) levels (main training effect, P lt 0.01). O-2(center dot-) increased after the soccer exercise (main exercise effect, P lt 0.01), but these changes reached statistical significance only in the P group (exercise x supplementation effect, P lt 0.05). TAS levels decreased significantly post- exercise only in P group (P lt 0.01). Both Asx and P groups experienced increase in total SH groups content (by 21% and 9%, respectively) and supplementation effect was marginally significant (P=0.08). Basal SOD activity significantly decreased both in P and in Asx group by the end of the study (main training effect, P lt 0.01). All participants showed a significant decrease in basal CK and AST activities after 90 days (main training effect, P lt 0.01 and P lt 0.001, respectively). CK and AST activities in serum significantly increased as result of soccer exercise (main exercise effect, P lt 0.001 and P lt 0.01, respectively). Postexercise CK and AST levels were significantly lower in Asx group compared to P group (P lt 0.05) Conclusion. The results of the present study suggest that soccer training and soccer exercise are associated with excessive production of free radicals and oxidative stress, which might diminish antioxidant system efficiency. Supplementation with Asx could prevent exercise induced free radical production and depletion of non-enzymatic antioxidant defense in young soccer players",
publisher = "Edizioni Minerva Medica, Turin",
journal = "Journal of Sports Medicine and Physical Fitness",
title = "Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players",
volume = "52",
number = "4",
pages = "382-392",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1654"
}

Đorđević, B., Baralić, I., Kotur-Stevuljević, J., Stefanović, A., Ivanišević, J., Radivojević, N., Anđelković, M.,& Dikić, N.. (2012). Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players. in Journal of Sports Medicine and Physical Fitness
Edizioni Minerva Medica, Turin., 52(4), 382-392.
https://hdl.handle.net/21.15107/rcub_farfar_1654

Đorđević B, Baralić I, Kotur-Stevuljević J, Stefanović A, Ivanišević J, Radivojević N, Anđelković M, Dikić N. Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players. in Journal of Sports Medicine and Physical Fitness. 2012;52(4):382-392.
https://hdl.handle.net/21.15107/rcub_farfar_1654 .

Đorđević, Brižita, Baralić, Ivana, Kotur-Stevuljević, Jelena, Stefanović, Aleksandra, Ivanišević, Jasmina, Radivojević, Nenad, Anđelković, Marija, Dikić, Nenad, "Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players" in Journal of Sports Medicine and Physical Fitness, 52, no. 4 (2012):382-392,
https://hdl.handle.net/21.15107/rcub_farfar_1654 .