TY  - JOUR
AU  - Kovač, Mirjana
AU  - Basarić, Dušica
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Backović, Dragana
AU  - Lalić-Ćosić, Sanja
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4437
AB  - Background/Aim. Direct oral anticoagulants (DOACs) administration significantly interferes with coagulation as-says. The aim of the study was to evaluate the effect of DOACs and DOAC-Remove® on coagulation assays dur-ing thrombophilia testing. Methods. The study was car-ried out from January 2019 to the end of June 2020. It in-cluded 30 DOAC-treated patients, 14 females and 16 males aged 23 to 63 (median age 47.6 years), tested for thrombophilia due to venous thromboembolism (VTE). Thrombophilia testing was performed using DOAC-Remove® tablets (activated charcoal). The results before and after DOAC-Remove® were compared. Results. Posi-tive lupus anticoagulant (LA) results were observed in 20% apixaban, 100% dabigatran, and 70% rivaroxaban-treated patients, while in samples after DOAC-Remove®, the LA positivity was observed only in one from the apix-aban group. Before DOAC-Remove®, the activated pro-tein C (APC) resistance (APC-R) was measurable in 40% dabigatran and 80% rivaroxaban-treated patients, while, after using DOAC-Remove®, the APC-R was measurable in all cases. Comparing the results obtained from the sam-ples before and after DOAC-Remove®, a difference was noted in relation to all dilute Russell's viper venom time (dRVVT) coagulation tests, except for the dRVVT ratio in the apixaban group. Clot-based methods for detecting the APC resistance were significantly affected by dabigatran and less by rivaroxaban. Conclusion. DOACs were prac-tically inactivated after the addition of the DOAC-Remove®, which made it possible to perform analyses for the LA and APC-R testing freely and obtain relevant re-sults.
AB  - Uvod/Cilj. Primena direktnih oralnih antikoagulansa (DOAK)
značajno utiče na testove koagulacije. Cilj rada bio je da se pro-
ceni uticaj DOAK i DOAC-Remove® tableta (aktivni ugalj) na
testove koagulacije tokom ispitivanja trombofilije. Metode.
Istraživanjem, sprovedenim od januara 2019. do juna 2020.
godine, obuhvaćeno je 30 bolesnika lečenih DOAK-om i
testiranih na trombofiliju zbog venskog tromboembolzma
(VTE). Bilo je 14 žena i 16 muškaraca, starosti od 23 do 63
godine (medijana 47,6 godina). Ispitivanje trombofilije izvršeno
je upotrebom DOAC-Remove® tableta (aktivni ugalj).
Upoređivani su rezultati pre i posle primene DOAC-Remove®.
Rezultati. Pozitivni rezultati za lupus antikoagulantni (LA) test
dobijeni su kod 20% bolesnika lečenih apiksabanom, kod
100% bolesnika lečenih dabigatranom i kod 70% lečenih riva-
roksabanom, a u uzorcima posle DOAC-Remove® pozitivnost
na LA dobijena je samo kod jednog bolesnika iz grupe lečnih
apiksabanom. Pre primene DOAC-Remove®, rezistencija na
aktivisani protein C (activated protein C resistance – APC-R) bila je
merljiva kod 40% i 80% bolesnika lečenih dabigatranom, od-
nosno rivaroksabanom, dok je posle primene DOAC-
Remove®, APC-R bila merljiva u svim slučajevima.
Upoređivanjem rezultata dobijenih iz uzoraka pre i posle
primene DOAC-Remove®, primećena je razlika u odnosu na
sve testove vremena koagulacije izvršene razblaženim Russell-
ovim zmijskim otrovom (dilute Russell’s viper venom time –
dRVVT), osim dRVVT u grupi bolesnika lečenih apiksabanom.
Na koagulacionu metodu za otkrivanje APC-R značajno je uti-
cao dabigatran, a manje rivaroksaban. Zaključak. Nakon
primene DOAC-Remove® tableta, DOAK su praktično
inaktivisani što je omogućilo izvođenje analiza za LA i APC-R i
dobijanje relevantnih rezultata testova.
PB  - Inst. Sci. inf., Univ. Defence in Belgrade
T2  - Vojnosanitetski Pregled
T1  - Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients
T1  - Uticaj DOAK i DOAC-REMOVE® na testove koagulacije u toku testiranja
trombofilije kod bolesnika lečenih primenom DOAK
VL  - 79
IS  - 12
SP  - 1248
EP  - 1254
DO  - 10.2298/VSP210217101K
ER  - 

@article{
author = "Kovač, Mirjana and Basarić, Dušica and Tomić, Branko and Gvozdenov, Maja and Backović, Dragana and Lalić-Ćosić, Sanja",
year = "2022",
abstract = "Background/Aim. Direct oral anticoagulants (DOACs) administration significantly interferes with coagulation as-says. The aim of the study was to evaluate the effect of DOACs and DOAC-Remove® on coagulation assays dur-ing thrombophilia testing. Methods. The study was car-ried out from January 2019 to the end of June 2020. It in-cluded 30 DOAC-treated patients, 14 females and 16 males aged 23 to 63 (median age 47.6 years), tested for thrombophilia due to venous thromboembolism (VTE). Thrombophilia testing was performed using DOAC-Remove® tablets (activated charcoal). The results before and after DOAC-Remove® were compared. Results. Posi-tive lupus anticoagulant (LA) results were observed in 20% apixaban, 100% dabigatran, and 70% rivaroxaban-treated patients, while in samples after DOAC-Remove®, the LA positivity was observed only in one from the apix-aban group. Before DOAC-Remove®, the activated pro-tein C (APC) resistance (APC-R) was measurable in 40% dabigatran and 80% rivaroxaban-treated patients, while, after using DOAC-Remove®, the APC-R was measurable in all cases. Comparing the results obtained from the sam-ples before and after DOAC-Remove®, a difference was noted in relation to all dilute Russell's viper venom time (dRVVT) coagulation tests, except for the dRVVT ratio in the apixaban group. Clot-based methods for detecting the APC resistance were significantly affected by dabigatran and less by rivaroxaban. Conclusion. DOACs were prac-tically inactivated after the addition of the DOAC-Remove®, which made it possible to perform analyses for the LA and APC-R testing freely and obtain relevant re-sults., Uvod/Cilj. Primena direktnih oralnih antikoagulansa (DOAK)
značajno utiče na testove koagulacije. Cilj rada bio je da se pro-
ceni uticaj DOAK i DOAC-Remove® tableta (aktivni ugalj) na
testove koagulacije tokom ispitivanja trombofilije. Metode.
Istraživanjem, sprovedenim od januara 2019. do juna 2020.
godine, obuhvaćeno je 30 bolesnika lečenih DOAK-om i
testiranih na trombofiliju zbog venskog tromboembolzma
(VTE). Bilo je 14 žena i 16 muškaraca, starosti od 23 do 63
godine (medijana 47,6 godina). Ispitivanje trombofilije izvršeno
je upotrebom DOAC-Remove® tableta (aktivni ugalj).
Upoređivani su rezultati pre i posle primene DOAC-Remove®.
Rezultati. Pozitivni rezultati za lupus antikoagulantni (LA) test
dobijeni su kod 20% bolesnika lečenih apiksabanom, kod
100% bolesnika lečenih dabigatranom i kod 70% lečenih riva-
roksabanom, a u uzorcima posle DOAC-Remove® pozitivnost
na LA dobijena je samo kod jednog bolesnika iz grupe lečnih
apiksabanom. Pre primene DOAC-Remove®, rezistencija na
aktivisani protein C (activated protein C resistance – APC-R) bila je
merljiva kod 40% i 80% bolesnika lečenih dabigatranom, od-
nosno rivaroksabanom, dok je posle primene DOAC-
Remove®, APC-R bila merljiva u svim slučajevima.
Upoređivanjem rezultata dobijenih iz uzoraka pre i posle
primene DOAC-Remove®, primećena je razlika u odnosu na
sve testove vremena koagulacije izvršene razblaženim Russell-
ovim zmijskim otrovom (dilute Russell’s viper venom time –
dRVVT), osim dRVVT u grupi bolesnika lečenih apiksabanom.
Na koagulacionu metodu za otkrivanje APC-R značajno je uti-
cao dabigatran, a manje rivaroksaban. Zaključak. Nakon
primene DOAC-Remove® tableta, DOAK su praktično
inaktivisani što je omogućilo izvođenje analiza za LA i APC-R i
dobijanje relevantnih rezultata testova.",
publisher = "Inst. Sci. inf., Univ. Defence in Belgrade",
journal = "Vojnosanitetski Pregled",
title = "Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients, Uticaj DOAK i DOAC-REMOVE® na testove koagulacije u toku testiranja
trombofilije kod bolesnika lečenih primenom DOAK",
volume = "79",
number = "12",
pages = "1248-1254",
doi = "10.2298/VSP210217101K"
}

Kovač, M., Basarić, D., Tomić, B., Gvozdenov, M., Backović, D.,& Lalić-Ćosić, S.. (2022). Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients. in Vojnosanitetski Pregled
Inst. Sci. inf., Univ. Defence in Belgrade., 79(12), 1248-1254.
https://doi.org/10.2298/VSP210217101K

Kovač M, Basarić D, Tomić B, Gvozdenov M, Backović D, Lalić-Ćosić S. Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients. in Vojnosanitetski Pregled. 2022;79(12):1248-1254.
doi:10.2298/VSP210217101K .

Kovač, Mirjana, Basarić, Dušica, Tomić, Branko, Gvozdenov, Maja, Backović, Dragana, Lalić-Ćosić, Sanja, "Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients" in Vojnosanitetski Pregled, 79, no. 12 (2022):1248-1254,
https://doi.org/10.2298/VSP210217101K . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Milovanović, V.
AU  - Lazić, Z.
AU  - Ivošević, A.
AU  - Radojković, Dragica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3134
AB  - Oxidative stress could reduce inhibitor activity of the alpha-1-antitrypsin (A1AT). Oxidative-modified A1AT (oxidized alpha-1-antitrypsin, OxyA1AT) significantly loses ability to protect the lungs from neutrophil elastase. We aimed to investigate OxyA1AT as a potential biomarker associated with onset and severity of chronic obstructive pulmonary disease (COPD) in adult population. The study included 65 patients with COPD (33 smokers and 32 no-smokers) and 46 healthy participants (17 smokers and 29 no-smokers). Determination of OxyA1AT in serum was based on the difference between the inhibitory activities of normal and oxidized A1AT against trypsin and elastase. The level of OxyA1AT was significantly increased in the group of COPD smokers compared to healthy no-smokers (p = 0.030) and COPD no-smokers (p = 0.009). The highest level of OxyA1AT was found in group of smokers with severe and very severe COPD in comparison to the following: no-smokers with the same stage of disease (p = 0.038), smokers with moderate COPD (p = 0.022), and the healthy control group, regardless of the smoking status (control no-smokers p = 0.001 and control smokers p = 0.034). In conclusion, serum level of OxyA1AT would be potentially good biomarker for the assessment of harmful effect of smoking to the onset and severity of COPD. Also, clinical significance of OxyA1AT as prognostic biomarker could be useful in assessing the effectiveness of antioxidant therapy for COPD and emphysema. Suitable and inexpensive laboratory method for determination of OxyA1AT is additional benefit for the introduction of OxyA1AT into routine clinical practice for diagnosis and monitoring of COPD.
PB  - Taylor & Francis Inc, Philadelphia
T2  - COPD-Journal of Chronic Obstructive Pulmonary Disease
T1  - Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population
VL  - 15
IS  - 5
SP  - 472
EP  - 478
DO  - 10.1080/15412555.2018.1541448
ER  - 

@article{
author = "Topić, Aleksandra and Milovanović, V. and Lazić, Z. and Ivošević, A. and Radojković, Dragica",
year = "2018",
abstract = "Oxidative stress could reduce inhibitor activity of the alpha-1-antitrypsin (A1AT). Oxidative-modified A1AT (oxidized alpha-1-antitrypsin, OxyA1AT) significantly loses ability to protect the lungs from neutrophil elastase. We aimed to investigate OxyA1AT as a potential biomarker associated with onset and severity of chronic obstructive pulmonary disease (COPD) in adult population. The study included 65 patients with COPD (33 smokers and 32 no-smokers) and 46 healthy participants (17 smokers and 29 no-smokers). Determination of OxyA1AT in serum was based on the difference between the inhibitory activities of normal and oxidized A1AT against trypsin and elastase. The level of OxyA1AT was significantly increased in the group of COPD smokers compared to healthy no-smokers (p = 0.030) and COPD no-smokers (p = 0.009). The highest level of OxyA1AT was found in group of smokers with severe and very severe COPD in comparison to the following: no-smokers with the same stage of disease (p = 0.038), smokers with moderate COPD (p = 0.022), and the healthy control group, regardless of the smoking status (control no-smokers p = 0.001 and control smokers p = 0.034). In conclusion, serum level of OxyA1AT would be potentially good biomarker for the assessment of harmful effect of smoking to the onset and severity of COPD. Also, clinical significance of OxyA1AT as prognostic biomarker could be useful in assessing the effectiveness of antioxidant therapy for COPD and emphysema. Suitable and inexpensive laboratory method for determination of OxyA1AT is additional benefit for the introduction of OxyA1AT into routine clinical practice for diagnosis and monitoring of COPD.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "COPD-Journal of Chronic Obstructive Pulmonary Disease",
title = "Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population",
volume = "15",
number = "5",
pages = "472-478",
doi = "10.1080/15412555.2018.1541448"
}

Topić, A., Milovanović, V., Lazić, Z., Ivošević, A.,& Radojković, D.. (2018). Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population. in COPD-Journal of Chronic Obstructive Pulmonary Disease
Taylor & Francis Inc, Philadelphia., 15(5), 472-478.
https://doi.org/10.1080/15412555.2018.1541448

Topić A, Milovanović V, Lazić Z, Ivošević A, Radojković D. Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population. in COPD-Journal of Chronic Obstructive Pulmonary Disease. 2018;15(5):472-478.
doi:10.1080/15412555.2018.1541448 .

Topić, Aleksandra, Milovanović, V., Lazić, Z., Ivošević, A., Radojković, Dragica, "Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population" in COPD-Journal of Chronic Obstructive Pulmonary Disease, 15, no. 5 (2018):472-478,
https://doi.org/10.1080/15412555.2018.1541448 . .

TY  - JOUR
AU  - Antonijević, Nebojša
AU  - Živković, Ivana D.
AU  - Jovanović, Ljubica M.
AU  - Matić, Dragan
AU  - Kocica, Mladen J.
AU  - Mrdović, Igor
AU  - Kanjuh, Vladimir
AU  - Ćulafić, Milica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2783
AB  - Background: The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration. The prominent one is reflected in the fact that dynamic impairment in renal function due to dehydratation may lead to haemorragic complications on the one hand, while on the other hand glomerular hyperfiltration may be a possible cause of dabigatran subdosing, hence reducing the drug's efficacy. Furthermore, limitations of the Cockcroft-Gault formula, considered a standard equation for assessing the renal function, may imply that other calculations are likely to obtain more accurate estimates of the kidney function in specific patient populations. Method and Conclusions: Although not routinely recommended, a possibility of monitoring dabigatran in special clinical settings adds to optimization of its dosage regimens, timely perioperative care and administration of urgently demanded thrombolytic therapy, therefore significantly improving this drug's safety profile. Despite the fact that dabigatran has fewer reported interactions with drugs, food constituents, and dietary supplements, certain interactions still remain, requiring considerable caution, notably in elderly, high bleeding risk patients, patients with decreased renal function and those on complex drug regimens. Additionally, upon approval of idarucizumab, an antidote to dabigatran solution, hitherto being a major safety concern, has been finally reached, which plays a vital role in life-threatening bleeding and emergency interventions and surgery.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Drug Metabolism
T1  - Dabigatran - Metabolism, Pharmacologic Properties and Drug Interactions
VL  - 18
IS  - 7
SP  - 622
EP  - 635
DO  - 10.2174/1389200218666170427113504
ER  - 

@article{
author = "Antonijević, Nebojša and Živković, Ivana D. and Jovanović, Ljubica M. and Matić, Dragan and Kocica, Mladen J. and Mrdović, Igor and Kanjuh, Vladimir and Ćulafić, Milica",
year = "2017",
abstract = "Background: The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration. The prominent one is reflected in the fact that dynamic impairment in renal function due to dehydratation may lead to haemorragic complications on the one hand, while on the other hand glomerular hyperfiltration may be a possible cause of dabigatran subdosing, hence reducing the drug's efficacy. Furthermore, limitations of the Cockcroft-Gault formula, considered a standard equation for assessing the renal function, may imply that other calculations are likely to obtain more accurate estimates of the kidney function in specific patient populations. Method and Conclusions: Although not routinely recommended, a possibility of monitoring dabigatran in special clinical settings adds to optimization of its dosage regimens, timely perioperative care and administration of urgently demanded thrombolytic therapy, therefore significantly improving this drug's safety profile. Despite the fact that dabigatran has fewer reported interactions with drugs, food constituents, and dietary supplements, certain interactions still remain, requiring considerable caution, notably in elderly, high bleeding risk patients, patients with decreased renal function and those on complex drug regimens. Additionally, upon approval of idarucizumab, an antidote to dabigatran solution, hitherto being a major safety concern, has been finally reached, which plays a vital role in life-threatening bleeding and emergency interventions and surgery.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Drug Metabolism",
title = "Dabigatran - Metabolism, Pharmacologic Properties and Drug Interactions",
volume = "18",
number = "7",
pages = "622-635",
doi = "10.2174/1389200218666170427113504"
}

Antonijević, N., Živković, I. D., Jovanović, L. M., Matić, D., Kocica, M. J., Mrdović, I., Kanjuh, V.,& Ćulafić, M.. (2017). Dabigatran - Metabolism, Pharmacologic Properties and Drug Interactions. in Current Drug Metabolism
Bentham Science Publ Ltd, Sharjah., 18(7), 622-635.
https://doi.org/10.2174/1389200218666170427113504

Antonijević N, Živković ID, Jovanović LM, Matić D, Kocica MJ, Mrdović I, Kanjuh V, Ćulafić M. Dabigatran - Metabolism, Pharmacologic Properties and Drug Interactions. in Current Drug Metabolism. 2017;18(7):622-635.
doi:10.2174/1389200218666170427113504 .

Antonijević, Nebojša, Živković, Ivana D., Jovanović, Ljubica M., Matić, Dragan, Kocica, Mladen J., Mrdović, Igor, Kanjuh, Vladimir, Ćulafić, Milica, "Dabigatran - Metabolism, Pharmacologic Properties and Drug Interactions" in Current Drug Metabolism, 18, no. 7 (2017):622-635,
https://doi.org/10.2174/1389200218666170427113504 . .

TY  - JOUR
AU  - Malić, Živka
AU  - Topić, Aleksandra
AU  - Francuski, Đorđe
AU  - Stanković, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Marković, Bojan
AU  - Radojković, Dragica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2903
AB  - The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.
PB  - Taylor & Francis Inc, Philadelphia
T2  - COPD-Journal of Chronic Obstructive Pulmonary Disease
T1  - Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults
VL  - 14
IS  - 1
SP  - 95
EP  - 104
DO  - 10.1080/15412555.2016.1199667
ER  - 

@article{
author = "Malić, Živka and Topić, Aleksandra and Francuski, Đorđe and Stanković, Marija and Nagorni-Obradović, Ljudmila and Marković, Bojan and Radojković, Dragica",
year = "2017",
abstract = "The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "COPD-Journal of Chronic Obstructive Pulmonary Disease",
title = "Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults",
volume = "14",
number = "1",
pages = "95-104",
doi = "10.1080/15412555.2016.1199667"
}

Malić, Ž., Topić, A., Francuski, Đ., Stanković, M., Nagorni-Obradović, L., Marković, B.,& Radojković, D.. (2017). Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults. in COPD-Journal of Chronic Obstructive Pulmonary Disease
Taylor & Francis Inc, Philadelphia., 14(1), 95-104.
https://doi.org/10.1080/15412555.2016.1199667

Malić Ž, Topić A, Francuski Đ, Stanković M, Nagorni-Obradović L, Marković B, Radojković D. Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults. in COPD-Journal of Chronic Obstructive Pulmonary Disease. 2017;14(1):95-104.
doi:10.1080/15412555.2016.1199667 .

Malić, Živka, Topić, Aleksandra, Francuski, Đorđe, Stanković, Marija, Nagorni-Obradović, Ljudmila, Marković, Bojan, Radojković, Dragica, "Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults" in COPD-Journal of Chronic Obstructive Pulmonary Disease, 14, no. 1 (2017):95-104,
https://doi.org/10.1080/15412555.2016.1199667 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Francuski, Đorđe
AU  - Nikolić, Aleksandra
AU  - Milošević, Katarina
AU  - Jovičić, Snežana
AU  - Marković, Bojan
AU  - Đukić, Mirjana
AU  - Radojković, Dragica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2833
AB  - Introduction: The significance of oxidative stress in pathogenesis of childhood asthma was recognized, but its role in the clinical manifestations of disease is still unclear. Materials and Methods: The study was conducted in 96 asthmatic children. The urinary biomarker of oxidative stress, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG/creatinine) was determined by using HPLC-MS/MS. ELISA was performed to measure myeloperoxidase (MPO) and Cu,Zn-superoxide dismutase (Cu, Zn-SOD) in serum. Results: Logistic regression analysis revealed that female gender, tobacco smoke exposure, and increased 8-oxodG/creatinine were associated with risk for intermittent asthma, while the positive allergy test and increased Cu, Zn-SOD were associated with eczema in asthmatic children. Higher MPO (p = 0.033), and percent of granulocytes (p = 0.030) were found in severe persistent asthma in comparison to intermittent or mild persistent asthma. Conclusion: The main findings that TSE-induced oxidative stress is a risk for intermittent asthma and eczema may be clinically significant for the disease prevention and therapeutic improvements.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Fetal and Pediatric Pathology
T1  - The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma
VL  - 36
IS  - 4
SP  - 294
EP  - 303
DO  - 10.1080/15513815.2017.1315199
ER  - 

@article{
author = "Topić, Aleksandra and Francuski, Đorđe and Nikolić, Aleksandra and Milošević, Katarina and Jovičić, Snežana and Marković, Bojan and Đukić, Mirjana and Radojković, Dragica",
year = "2017",
abstract = "Introduction: The significance of oxidative stress in pathogenesis of childhood asthma was recognized, but its role in the clinical manifestations of disease is still unclear. Materials and Methods: The study was conducted in 96 asthmatic children. The urinary biomarker of oxidative stress, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG/creatinine) was determined by using HPLC-MS/MS. ELISA was performed to measure myeloperoxidase (MPO) and Cu,Zn-superoxide dismutase (Cu, Zn-SOD) in serum. Results: Logistic regression analysis revealed that female gender, tobacco smoke exposure, and increased 8-oxodG/creatinine were associated with risk for intermittent asthma, while the positive allergy test and increased Cu, Zn-SOD were associated with eczema in asthmatic children. Higher MPO (p = 0.033), and percent of granulocytes (p = 0.030) were found in severe persistent asthma in comparison to intermittent or mild persistent asthma. Conclusion: The main findings that TSE-induced oxidative stress is a risk for intermittent asthma and eczema may be clinically significant for the disease prevention and therapeutic improvements.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Fetal and Pediatric Pathology",
title = "The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma",
volume = "36",
number = "4",
pages = "294-303",
doi = "10.1080/15513815.2017.1315199"
}

Topić, A., Francuski, Đ., Nikolić, A., Milošević, K., Jovičić, S., Marković, B., Đukić, M.,& Radojković, D.. (2017). The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma. in Fetal and Pediatric Pathology
Taylor & Francis Inc, Philadelphia., 36(4), 294-303.
https://doi.org/10.1080/15513815.2017.1315199

Topić A, Francuski Đ, Nikolić A, Milošević K, Jovičić S, Marković B, Đukić M, Radojković D. The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma. in Fetal and Pediatric Pathology. 2017;36(4):294-303.
doi:10.1080/15513815.2017.1315199 .

Topić, Aleksandra, Francuski, Đorđe, Nikolić, Aleksandra, Milošević, Katarina, Jovičić, Snežana, Marković, Bojan, Đukić, Mirjana, Radojković, Dragica, "The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma" in Fetal and Pediatric Pathology, 36, no. 4 (2017):294-303,
https://doi.org/10.1080/15513815.2017.1315199 . .

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakicević, Ljiljana
AU  - Novković, Mirjana
AU  - Kusić-Tisma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, Evgenija
AU  - Čalija, Branko
AU  - Radak, Đorđe
AU  - Kovac, Mirjana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2756
AB  - Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Vascular Pharmacology
T1  - Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study
VL  - 14
IS  - 6
SP  - 563
EP  - 569
DO  - 10.2174/1570161114666160714103148
ER  - 

@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakicević, Ljiljana and Novković, Mirjana and Kusić-Tisma, Jelena and Radojković, Dragica and Strugarević, Evgenija and Čalija, Branko and Radak, Đorđe and Kovac, Mirjana",
year = "2016",
abstract = "Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Vascular Pharmacology",
title = "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study",
volume = "14",
number = "6",
pages = "563-569",
doi = "10.2174/1570161114666160714103148"
}

Backović, D., Ignjatović, S., Rakicević, L., Novković, M., Kusić-Tisma, J., Radojković, D., Strugarević, E., Čalija, B., Radak, Đ.,& Kovac, M.. (2016). Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology
Bentham Science Publ Ltd, Sharjah., 14(6), 563-569.
https://doi.org/10.2174/1570161114666160714103148

Backović D, Ignjatović S, Rakicević L, Novković M, Kusić-Tisma J, Radojković D, Strugarević E, Čalija B, Radak Đ, Kovac M. Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology. 2016;14(6):563-569.
doi:10.2174/1570161114666160714103148 .

Backović, Dragana, Ignjatović, Svetlana, Rakicević, Ljiljana, Novković, Mirjana, Kusić-Tisma, Jelena, Radojković, Dragica, Strugarević, Evgenija, Čalija, Branko, Radak, Đorđe, Kovac, Mirjana, "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study" in Current Vascular Pharmacology, 14, no. 6 (2016):563-569,
https://doi.org/10.2174/1570161114666160714103148 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Nagorni-Obradović, Ljudmila
AU  - Francuski, Đorđe
AU  - Ljujić, Mila
AU  - Malić, Živka
AU  - Radojković, Dragica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2771
AB  - Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.
PB  - Springer/Plenum Publishers, New York
T2  - Biochemical Genetics
T1  - Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency
VL  - 54
IS  - 5
SP  - 746
EP  - 752
DO  - 10.1007/s10528-016-9748-7
ER  - 

@article{
author = "Topić, Aleksandra and Nagorni-Obradović, Ljudmila and Francuski, Đorđe and Ljujić, Mila and Malić, Živka and Radojković, Dragica",
year = "2016",
abstract = "Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Biochemical Genetics",
title = "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency",
volume = "54",
number = "5",
pages = "746-752",
doi = "10.1007/s10528-016-9748-7"
}

Topić, A., Nagorni-Obradović, L., Francuski, Đ., Ljujić, M., Malić, Ž.,& Radojković, D.. (2016). Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics
Springer/Plenum Publishers, New York., 54(5), 746-752.
https://doi.org/10.1007/s10528-016-9748-7

Topić A, Nagorni-Obradović L, Francuski Đ, Ljujić M, Malić Ž, Radojković D. Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics. 2016;54(5):746-752.
doi:10.1007/s10528-016-9748-7 .

Topić, Aleksandra, Nagorni-Obradović, Ljudmila, Francuski, Đorđe, Ljujić, Mila, Malić, Živka, Radojković, Dragica, "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency" in Biochemical Genetics, 54, no. 5 (2016):746-752,
https://doi.org/10.1007/s10528-016-9748-7 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Malić, Živka
AU  - Francuski, Đorđe
AU  - Stanković, Marija
AU  - Marković, Bojan
AU  - Soskić, Blagoje
AU  - Tomić, Branko
AU  - Ilić, Stefan
AU  - Dobrivojević, Snežana
AU  - Drca, Sanja
AU  - Radojković, Dragica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2600
AB  - Gender-related differences in the association between polymorphism of xenobiotic-metabolising enzymes or non-genetic biomarkers and susceptibility to oxidative stress was assessed in healthy middle-aged Serbian adults, by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG/creatinine) and total antioxidant status in serum (TAOS). Females were more susceptible to oxidative stress. In both genders, positive predictor of the antioxidative protection was serum triglyceride, while BMI  lt 25 kg/m(2) was associated with oxidative stress. Susceptibility to oxidative stress in males was associated with GSTT1*null allele and increased serum iron, but in females, it was decreased serum bilirubin. Early identification of the risk factors could be important in the prevention of oxidative stress-related diseases.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Biomarkers
T1  - Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults
VL  - 21
IS  - 2
SP  - 186
EP  - 193
DO  - 10.3109/1354750X.2015.1126647
ER  - 

@article{
author = "Topić, Aleksandra and Malić, Živka and Francuski, Đorđe and Stanković, Marija and Marković, Bojan and Soskić, Blagoje and Tomić, Branko and Ilić, Stefan and Dobrivojević, Snežana and Drca, Sanja and Radojković, Dragica",
year = "2016",
abstract = "Gender-related differences in the association between polymorphism of xenobiotic-metabolising enzymes or non-genetic biomarkers and susceptibility to oxidative stress was assessed in healthy middle-aged Serbian adults, by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG/creatinine) and total antioxidant status in serum (TAOS). Females were more susceptible to oxidative stress. In both genders, positive predictor of the antioxidative protection was serum triglyceride, while BMI  lt 25 kg/m(2) was associated with oxidative stress. Susceptibility to oxidative stress in males was associated with GSTT1*null allele and increased serum iron, but in females, it was decreased serum bilirubin. Early identification of the risk factors could be important in the prevention of oxidative stress-related diseases.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Biomarkers",
title = "Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults",
volume = "21",
number = "2",
pages = "186-193",
doi = "10.3109/1354750X.2015.1126647"
}

Topić, A., Malić, Ž., Francuski, Đ., Stanković, M., Marković, B., Soskić, B., Tomić, B., Ilić, S., Dobrivojević, S., Drca, S.,& Radojković, D.. (2016). Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults. in Biomarkers
Taylor & Francis Ltd, Abingdon., 21(2), 186-193.
https://doi.org/10.3109/1354750X.2015.1126647

Topić A, Malić Ž, Francuski Đ, Stanković M, Marković B, Soskić B, Tomić B, Ilić S, Dobrivojević S, Drca S, Radojković D. Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults. in Biomarkers. 2016;21(2):186-193.
doi:10.3109/1354750X.2015.1126647 .

Topić, Aleksandra, Malić, Živka, Francuski, Đorđe, Stanković, Marija, Marković, Bojan, Soskić, Blagoje, Tomić, Branko, Ilić, Stefan, Dobrivojević, Snežana, Drca, Sanja, Radojković, Dragica, "Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults" in Biomarkers, 21, no. 2 (2016):186-193,
https://doi.org/10.3109/1354750X.2015.1126647 . .

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakicević, Ljiljana
AU  - Kusić-Tisma, Jelena
AU  - Radojković, Dragica
AU  - Čalija, Branko
AU  - Strugarević, Evgenija
AU  - Radak, Đorđe
AU  - Kovac, Mirjana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2573
AB  - Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the CYP2C19*2 allele vs. wild type (OR 4.250, 95% CI 1.695-10.658, P lt 0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis
VL  - 35
IS  - 1
SP  - 26
EP  - 33
DO  - 10.1515/jomb-2015-0009
ER  - 

@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakicević, Ljiljana and Kusić-Tisma, Jelena and Radojković, Dragica and Čalija, Branko and Strugarević, Evgenija and Radak, Đorđe and Kovac, Mirjana",
year = "2016",
abstract = "Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the CYP2C19*2 allele vs. wild type (OR 4.250, 95% CI 1.695-10.658, P lt 0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis",
volume = "35",
number = "1",
pages = "26-33",
doi = "10.1515/jomb-2015-0009"
}

Backović, D., Ignjatović, S., Rakicević, L., Kusić-Tisma, J., Radojković, D., Čalija, B., Strugarević, E., Radak, Đ.,& Kovac, M.. (2016). Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 35(1), 26-33.
https://doi.org/10.1515/jomb-2015-0009

Backović D, Ignjatović S, Rakicević L, Kusić-Tisma J, Radojković D, Čalija B, Strugarević E, Radak Đ, Kovac M. Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis. in Journal of Medical Biochemistry. 2016;35(1):26-33.
doi:10.1515/jomb-2015-0009 .

Backović, Dragana, Ignjatović, Svetlana, Rakicević, Ljiljana, Kusić-Tisma, Jelena, Radojković, Dragica, Čalija, Branko, Strugarević, Evgenija, Radak, Đorđe, Kovac, Mirjana, "Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis" in Journal of Medical Biochemistry, 35, no. 1 (2016):26-33,
https://doi.org/10.1515/jomb-2015-0009 . .

TY  - JOUR
AU  - Petrović-Stanojević, Nataša
AU  - Topić, Aleksandra
AU  - Nikolić, Aleksandra
AU  - Stankovic, Marija
AU  - Dopuđa-Pantić, Vesna
AU  - Milenković, Branislava
AU  - Radojković, Dragica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2142
AB  - Background and Objectives Polymorphisms of beta2-adrenergic receptor gene (ADRB2) are clinically relevant for several reasons, including as a risk factor for asthma development/severity and predicting the effectiveness of treatment with beta2-agonists in reducing asthma symptoms. The aim of this study was to examine the association between ADRB2 gene polymorphisms and asthma in the Serbian population, and to evaluate the therapeutic response in relation to the ADRB2 genotype. Methods The study included 171 patients with asthma and 101 healthy subjects as the control group. Genotyping of Arg16Gly and Gln27Glu polymorphisms was performed by direct sequencing of polymerase chain reaction (PCR) products. Results In Serbian adults, carriers of the 27Gln allele and 27Gln/Gln genotype were at higher risk of asthma [odds ratio (OR) 2.5, 95 % confidence interval (CI) 1.6-3.8, and OR 3.00, 95 % CI 1.7-5.3, respectively], while the presence of the 27Glu allele and 27Gln/Glu genotype were found to be protective of asthma (OR 0.4, 95 % CI 0.3-0.6, and OR 0.3, 95 % CI 0.1-0.7, respectively). Furthermore, we found that the presence of the 27Gln allele in asthmatics younger than 50 years leads to a better response to therapy with long-acting beta2-agonists (LABA) in combination with prevailing low and moderate doses of inhaled corticosteroids (ICS), while carriers of the 27Glu allele over 50 years old are more likely to respond to LABA + ICS therapy. Conclusion We identified that in Serbian adults the 27Gln allele and 27Gln homozygosity are risk factors for asthma, which may be of clinical interest in disease prevention. The finding that younger carriers of the 27Gln allele respond better to LABA + ICS therapy may be utilized in personalized asthma treatment.
PB  - Adis Int Ltd, Northcote
T2  - Molecular Diagnosis & Therapy
T1  - Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists
VL  - 18
IS  - 6
SP  - 639
EP  - 646
DO  - 10.1007/s40291-014-0116-1
ER  - 

@article{
author = "Petrović-Stanojević, Nataša and Topić, Aleksandra and Nikolić, Aleksandra and Stankovic, Marija and Dopuđa-Pantić, Vesna and Milenković, Branislava and Radojković, Dragica",
year = "2014",
abstract = "Background and Objectives Polymorphisms of beta2-adrenergic receptor gene (ADRB2) are clinically relevant for several reasons, including as a risk factor for asthma development/severity and predicting the effectiveness of treatment with beta2-agonists in reducing asthma symptoms. The aim of this study was to examine the association between ADRB2 gene polymorphisms and asthma in the Serbian population, and to evaluate the therapeutic response in relation to the ADRB2 genotype. Methods The study included 171 patients with asthma and 101 healthy subjects as the control group. Genotyping of Arg16Gly and Gln27Glu polymorphisms was performed by direct sequencing of polymerase chain reaction (PCR) products. Results In Serbian adults, carriers of the 27Gln allele and 27Gln/Gln genotype were at higher risk of asthma [odds ratio (OR) 2.5, 95 % confidence interval (CI) 1.6-3.8, and OR 3.00, 95 % CI 1.7-5.3, respectively], while the presence of the 27Glu allele and 27Gln/Glu genotype were found to be protective of asthma (OR 0.4, 95 % CI 0.3-0.6, and OR 0.3, 95 % CI 0.1-0.7, respectively). Furthermore, we found that the presence of the 27Gln allele in asthmatics younger than 50 years leads to a better response to therapy with long-acting beta2-agonists (LABA) in combination with prevailing low and moderate doses of inhaled corticosteroids (ICS), while carriers of the 27Glu allele over 50 years old are more likely to respond to LABA + ICS therapy. Conclusion We identified that in Serbian adults the 27Gln allele and 27Gln homozygosity are risk factors for asthma, which may be of clinical interest in disease prevention. The finding that younger carriers of the 27Gln allele respond better to LABA + ICS therapy may be utilized in personalized asthma treatment.",
publisher = "Adis Int Ltd, Northcote",
journal = "Molecular Diagnosis & Therapy",
title = "Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists",
volume = "18",
number = "6",
pages = "639-646",
doi = "10.1007/s40291-014-0116-1"
}

Petrović-Stanojević, N., Topić, A., Nikolić, A., Stankovic, M., Dopuđa-Pantić, V., Milenković, B.,& Radojković, D.. (2014). Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists. in Molecular Diagnosis & Therapy
Adis Int Ltd, Northcote., 18(6), 639-646.
https://doi.org/10.1007/s40291-014-0116-1

Petrović-Stanojević N, Topić A, Nikolić A, Stankovic M, Dopuđa-Pantić V, Milenković B, Radojković D. Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists. in Molecular Diagnosis & Therapy. 2014;18(6):639-646.
doi:10.1007/s40291-014-0116-1 .

Petrović-Stanojević, Nataša, Topić, Aleksandra, Nikolić, Aleksandra, Stankovic, Marija, Dopuđa-Pantić, Vesna, Milenković, Branislava, Radojković, Dragica, "Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists" in Molecular Diagnosis & Therapy, 18, no. 6 (2014):639-646,
https://doi.org/10.1007/s40291-014-0116-1 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Francuski, Đorđe
AU  - Marković, Bojan
AU  - Stanković, Marija
AU  - Dobrivojević, Snežana
AU  - Drca, Sanja
AU  - Radojković, Dragica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1917
AB  - Objectives: Although there are many nucleobase modifications, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is one of the dominant form of oxidative modifications of DNA. Urinary 8-oxodG is potentially the best non-invasive biomarker of oxidative stress. Defining reference interval for urinary 8-oxodG is a prerequisite for its clinical use as biomarker. Design and methods: Reference population included 229 healthy Serbian adults (130 males and 99 females). The spot urinary 8-oxodG was determined using high performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Urinary creatinine was measured by the kinetic Jaffe method. Results: Analytical performances of the HPLC-MS/MS: CVs within and between-run variations were 5.6% and 2.6%; LOD and LOQ were 1.65 nmol/L and 330 nmol/L; mean recovery and relative accuracy were 96% and 97%. Creatinine level was higher in males than in females, but no gender difference in 8-oxodG level was observed. Upon the adjustment of 8-oxodG to creatinine (8-oxodG/creatinine), higher values were obtained in females (1.38 +/- 0.65 nmol/mmol) than in males (1.05 +/- 0.48 nmol/mmol). Distribution of 8-oxodG/creatinine in spot urine sample was log-normal and gender-related reference intervals (estimated as the 2.5th-97.5th percentiles) were 0.45-2.22 nmol/mmol for males, and 0.54-3.11 nmol/mmol for females. Body mass index (BMI) affects excretion of the 8-oxodG in males, independently of urinary creatinine, while in females it does not. Therefore, BMI might contribute to the gender-related differences of 8-oxodG/creatinine in spot urine samples. Conclusions: This is the first established gender-related reference intervals of spot urinary 8-oxodG/creatinine. Our results contribute to the full validation of 8-oxodG as biomarker of oxidative stress.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Clinical Biochemistry
T1  - Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population
VL  - 46
IS  - 4-5
SP  - 321
EP  - 326
DO  - 10.1016/j.clinbiochem.2012.12.008
ER  - 

@article{
author = "Topić, Aleksandra and Francuski, Đorđe and Marković, Bojan and Stanković, Marija and Dobrivojević, Snežana and Drca, Sanja and Radojković, Dragica",
year = "2013",
abstract = "Objectives: Although there are many nucleobase modifications, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is one of the dominant form of oxidative modifications of DNA. Urinary 8-oxodG is potentially the best non-invasive biomarker of oxidative stress. Defining reference interval for urinary 8-oxodG is a prerequisite for its clinical use as biomarker. Design and methods: Reference population included 229 healthy Serbian adults (130 males and 99 females). The spot urinary 8-oxodG was determined using high performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Urinary creatinine was measured by the kinetic Jaffe method. Results: Analytical performances of the HPLC-MS/MS: CVs within and between-run variations were 5.6% and 2.6%; LOD and LOQ were 1.65 nmol/L and 330 nmol/L; mean recovery and relative accuracy were 96% and 97%. Creatinine level was higher in males than in females, but no gender difference in 8-oxodG level was observed. Upon the adjustment of 8-oxodG to creatinine (8-oxodG/creatinine), higher values were obtained in females (1.38 +/- 0.65 nmol/mmol) than in males (1.05 +/- 0.48 nmol/mmol). Distribution of 8-oxodG/creatinine in spot urine sample was log-normal and gender-related reference intervals (estimated as the 2.5th-97.5th percentiles) were 0.45-2.22 nmol/mmol for males, and 0.54-3.11 nmol/mmol for females. Body mass index (BMI) affects excretion of the 8-oxodG in males, independently of urinary creatinine, while in females it does not. Therefore, BMI might contribute to the gender-related differences of 8-oxodG/creatinine in spot urine samples. Conclusions: This is the first established gender-related reference intervals of spot urinary 8-oxodG/creatinine. Our results contribute to the full validation of 8-oxodG as biomarker of oxidative stress.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Clinical Biochemistry",
title = "Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population",
volume = "46",
number = "4-5",
pages = "321-326",
doi = "10.1016/j.clinbiochem.2012.12.008"
}

Topić, A., Francuski, Đ., Marković, B., Stanković, M., Dobrivojević, S., Drca, S.,& Radojković, D.. (2013). Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population. in Clinical Biochemistry
Pergamon-Elsevier Science Ltd, Oxford., 46(4-5), 321-326.
https://doi.org/10.1016/j.clinbiochem.2012.12.008

Topić A, Francuski Đ, Marković B, Stanković M, Dobrivojević S, Drca S, Radojković D. Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population. in Clinical Biochemistry. 2013;46(4-5):321-326.
doi:10.1016/j.clinbiochem.2012.12.008 .

Topić, Aleksandra, Francuski, Đorđe, Marković, Bojan, Stanković, Marija, Dobrivojević, Snežana, Drca, Sanja, Radojković, Dragica, "Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population" in Clinical Biochemistry, 46, no. 4-5 (2013):321-326,
https://doi.org/10.1016/j.clinbiochem.2012.12.008 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Đukić, Mirjana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1903
AB  - Alcohol biomarkers play a significant role in the early diagnosis of alcohol intoxication/abuse, alcohol-related organ damages, assessment of alcoholism therapy outcomes, and in forensic medicine. Laboratory detection of excessive alcohol consumption can be carried out by direct measuring of the ethanol and/or metabolites in biological samples which is of particular importance in the cases of acute ethanol intoxication/controlling and/or monitoring of alcohol consumption, or indirectly, by using biomarkers. Preferred diagnostic characteristics of alcohol biomarkers, specificity and sensitivity dependent on the particular demands such as: prevention and treatment of alcoholism in primary and social care, criminal justice, workplace health and safety screening, trafficking control, etc. Alcohol biomarkers traditionally used in clinical practice [blood alcohol concentration (BAC), gamma-glutamyl transferase (GGT), carbohydrate-deficient transferrin (CDT), the ratio GGT/CDT, alanine aminotransferase (ALT), aspartate aminotransferase (AST), the ratio AST/ALT, mean corpuscular volume (MCV), phosphatidylethanol (PEth)] are well validated. They are used as screening/monitoring markers of acute/chronic excessive alcohol intake, alcoholism in pregnancy, and other disorders/conditions related to alcohol abuse. Numerous potential alcohol biomarkers have been discovered, but few are validated. Potential alcohol biomarkers (ethanol and serotonin metabolites, sialic acids, etc.) have good diagnostic characteristics, but their application in clinical practice is limited due to the costly equipment necessary for their measurement. Significant progress has been made in the development of sensitive and practical alcohol transdermal devices that can instantly/continuously measure BAC through human skin. Transdermal sensing of alcohol may become a valuable method for monitoring abstinence. A special aspect of alcoholism is genetic predisposition to alcohol abuse and alcoholism, or alcohol-related organ damage. Recent genome-wide association studies (GWASs) have proposed several susceptibility loci for alcohol dependence.
PB  - Clin Lab Publ, Heidelberg
T2  - Clinical Laboratory
T1  - Diagnostic Characteristics and Application of Alcohol Biomarkers
VL  - 59
IS  - 3-4
SP  - 233
EP  - 245
DO  - 10.7754/Clin.Lab.2012.120318
ER  - 

@article{
author = "Topić, Aleksandra and Đukić, Mirjana",
year = "2013",
abstract = "Alcohol biomarkers play a significant role in the early diagnosis of alcohol intoxication/abuse, alcohol-related organ damages, assessment of alcoholism therapy outcomes, and in forensic medicine. Laboratory detection of excessive alcohol consumption can be carried out by direct measuring of the ethanol and/or metabolites in biological samples which is of particular importance in the cases of acute ethanol intoxication/controlling and/or monitoring of alcohol consumption, or indirectly, by using biomarkers. Preferred diagnostic characteristics of alcohol biomarkers, specificity and sensitivity dependent on the particular demands such as: prevention and treatment of alcoholism in primary and social care, criminal justice, workplace health and safety screening, trafficking control, etc. Alcohol biomarkers traditionally used in clinical practice [blood alcohol concentration (BAC), gamma-glutamyl transferase (GGT), carbohydrate-deficient transferrin (CDT), the ratio GGT/CDT, alanine aminotransferase (ALT), aspartate aminotransferase (AST), the ratio AST/ALT, mean corpuscular volume (MCV), phosphatidylethanol (PEth)] are well validated. They are used as screening/monitoring markers of acute/chronic excessive alcohol intake, alcoholism in pregnancy, and other disorders/conditions related to alcohol abuse. Numerous potential alcohol biomarkers have been discovered, but few are validated. Potential alcohol biomarkers (ethanol and serotonin metabolites, sialic acids, etc.) have good diagnostic characteristics, but their application in clinical practice is limited due to the costly equipment necessary for their measurement. Significant progress has been made in the development of sensitive and practical alcohol transdermal devices that can instantly/continuously measure BAC through human skin. Transdermal sensing of alcohol may become a valuable method for monitoring abstinence. A special aspect of alcoholism is genetic predisposition to alcohol abuse and alcoholism, or alcohol-related organ damage. Recent genome-wide association studies (GWASs) have proposed several susceptibility loci for alcohol dependence.",
publisher = "Clin Lab Publ, Heidelberg",
journal = "Clinical Laboratory",
title = "Diagnostic Characteristics and Application of Alcohol Biomarkers",
volume = "59",
number = "3-4",
pages = "233-245",
doi = "10.7754/Clin.Lab.2012.120318"
}

Topić, A.,& Đukić, M.. (2013). Diagnostic Characteristics and Application of Alcohol Biomarkers. in Clinical Laboratory
Clin Lab Publ, Heidelberg., 59(3-4), 233-245.
https://doi.org/10.7754/Clin.Lab.2012.120318

Topić A, Đukić M. Diagnostic Characteristics and Application of Alcohol Biomarkers. in Clinical Laboratory. 2013;59(3-4):233-245.
doi:10.7754/Clin.Lab.2012.120318 .

Topić, Aleksandra, Đukić, Mirjana, "Diagnostic Characteristics and Application of Alcohol Biomarkers" in Clinical Laboratory, 59, no. 3-4 (2013):233-245,
https://doi.org/10.7754/Clin.Lab.2012.120318 . .

TY  - JOUR
AU  - Đukić, Mirjana
AU  - Jovanović, Marina
AU  - Ninković, Milica
AU  - Stevanović, Ivana
AU  - Ćurčić, Marijana
AU  - Topić, Aleksandra
AU  - Vujanović, Dragana
AU  - Đurđević, Dragan
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1663
AB  - Introduction: Contact herbicide diquat (DQ), redox cycling compound, mediates its systemic toxicity throughout the enlarged production of free radicals. Target organs are liver and kidney in humans. To-date, the mechanism of DQ-induced neurotoxicity has not been rationalized. Objective: The objectives of the study were to examine the ability of DQ to induce oxidative stress (OS) and/or nitrosative stress (NS) upon intrastriatal (i.s.) administration and to investigate the role of nitric oxide (NOx) using NG-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) in the pretreatment of DQ i.s. administration. Material and Methods: The experiment was conducted on Wistar rats, randomly divided in experimental groups, receiving different treatments i.s. applied. Parameters of OS/NS such as: superoxide anion radical (O-2(center dot-)), superoxide dismutase (SOD), malondialdehyde (MDA) and nitrates (NO3-) were measured in the cortex (bilaterally), at 30th min, 24 hours and 7 days after the treatments. Results: Lethargy and high mortality rate were observed only in the DQ group (within 24 hours and 2-3 hours, respectively) after awakening from anesthesia. Markedly increased production of NOx and O-2(center dot-) along with elevated lipid peroxidation altogether contributed to DQ neurotoxicity. The most importantly, the L-NAME i.s. pretreatment protected treated animals from dying and diminished OS/NS response against DQ-induced neurotoxicity. Conclusion: The i.s. pretreatment with L-NAME resulted in neuroprotection against DQ neurotoxity, based on animal survival and reduced LPO in the cortex.
PB  - Inst Agricultural Medicine, Lublin
T2  - Annals of Agricultural and Environmental Medicine
T1  - Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity
VL  - 19
IS  - 4
SP  - 666
EP  - 672
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1663
ER  - 

@article{
author = "Đukić, Mirjana and Jovanović, Marina and Ninković, Milica and Stevanović, Ivana and Ćurčić, Marijana and Topić, Aleksandra and Vujanović, Dragana and Đurđević, Dragan",
year = "2012",
abstract = "Introduction: Contact herbicide diquat (DQ), redox cycling compound, mediates its systemic toxicity throughout the enlarged production of free radicals. Target organs are liver and kidney in humans. To-date, the mechanism of DQ-induced neurotoxicity has not been rationalized. Objective: The objectives of the study were to examine the ability of DQ to induce oxidative stress (OS) and/or nitrosative stress (NS) upon intrastriatal (i.s.) administration and to investigate the role of nitric oxide (NOx) using NG-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) in the pretreatment of DQ i.s. administration. Material and Methods: The experiment was conducted on Wistar rats, randomly divided in experimental groups, receiving different treatments i.s. applied. Parameters of OS/NS such as: superoxide anion radical (O-2(center dot-)), superoxide dismutase (SOD), malondialdehyde (MDA) and nitrates (NO3-) were measured in the cortex (bilaterally), at 30th min, 24 hours and 7 days after the treatments. Results: Lethargy and high mortality rate were observed only in the DQ group (within 24 hours and 2-3 hours, respectively) after awakening from anesthesia. Markedly increased production of NOx and O-2(center dot-) along with elevated lipid peroxidation altogether contributed to DQ neurotoxicity. The most importantly, the L-NAME i.s. pretreatment protected treated animals from dying and diminished OS/NS response against DQ-induced neurotoxicity. Conclusion: The i.s. pretreatment with L-NAME resulted in neuroprotection against DQ neurotoxity, based on animal survival and reduced LPO in the cortex.",
publisher = "Inst Agricultural Medicine, Lublin",
journal = "Annals of Agricultural and Environmental Medicine",
title = "Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity",
volume = "19",
number = "4",
pages = "666-672",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1663"
}

Đukić, M., Jovanović, M., Ninković, M., Stevanović, I., Ćurčić, M., Topić, A., Vujanović, D.,& Đurđević, D.. (2012). Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity. in Annals of Agricultural and Environmental Medicine
Inst Agricultural Medicine, Lublin., 19(4), 666-672.
https://hdl.handle.net/21.15107/rcub_farfar_1663

Đukić M, Jovanović M, Ninković M, Stevanović I, Ćurčić M, Topić A, Vujanović D, Đurđević D. Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity. in Annals of Agricultural and Environmental Medicine. 2012;19(4):666-672.
https://hdl.handle.net/21.15107/rcub_farfar_1663 .

Đukić, Mirjana, Jovanović, Marina, Ninković, Milica, Stevanović, Ivana, Ćurčić, Marijana, Topić, Aleksandra, Vujanović, Dragana, Đurđević, Dragan, "Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxcity" in Annals of Agricultural and Environmental Medicine, 19, no. 4 (2012):666-672,
https://hdl.handle.net/21.15107/rcub_farfar_1663 .

TY  - JOUR
AU  - Francuski, Bojana M.
AU  - Ivković, Branka
AU  - Stojanović, I
AU  - Vladimirov, S
AU  - Francuski, Đorđe
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1800
AB  - In the title compound, C16H11F3O 2, the -pyran-one ring adopts an envelope conformation with the chiral C atom standing out of the ring plane. In the crystal, molecules are linked by C - H⋯O and C - H⋯F inter-actions.
PB  - International Union of Crystallography
T2  - Acta Crystallographica Section E: Structure Reports Online
T1  - 2-[2-(Trifluoromethyl)phenyl]-2H-1-benzopyran-4(3H)-one
VL  - 68
IS  - 5
DO  - 10.1107/S160053681201687X
ER  - 

@article{
author = "Francuski, Bojana M. and Ivković, Branka and Stojanović, I and Vladimirov, S and Francuski, Đorđe",
year = "2012",
abstract = "In the title compound, C16H11F3O 2, the -pyran-one ring adopts an envelope conformation with the chiral C atom standing out of the ring plane. In the crystal, molecules are linked by C - H⋯O and C - H⋯F inter-actions.",
publisher = "International Union of Crystallography",
journal = "Acta Crystallographica Section E: Structure Reports Online",
title = "2-[2-(Trifluoromethyl)phenyl]-2H-1-benzopyran-4(3H)-one",
volume = "68",
number = "5",
doi = "10.1107/S160053681201687X"
}

Francuski, B. M., Ivković, B., Stojanović, I., Vladimirov, S.,& Francuski, Đ.. (2012). 2-[2-(Trifluoromethyl)phenyl]-2H-1-benzopyran-4(3H)-one. in Acta Crystallographica Section E: Structure Reports Online
International Union of Crystallography., 68(5).
https://doi.org/10.1107/S160053681201687X

Francuski BM, Ivković B, Stojanović I, Vladimirov S, Francuski Đ. 2-[2-(Trifluoromethyl)phenyl]-2H-1-benzopyran-4(3H)-one. in Acta Crystallographica Section E: Structure Reports Online. 2012;68(5).
doi:10.1107/S160053681201687X .

Francuski, Bojana M., Ivković, Branka, Stojanović, I, Vladimirov, S, Francuski, Đorđe, "2-[2-(Trifluoromethyl)phenyl]-2H-1-benzopyran-4(3H)-one" in Acta Crystallographica Section E: Structure Reports Online, 68, no. 5 (2012),
https://doi.org/10.1107/S160053681201687X . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Stankovic, Marija
AU  - Divac-Rankov, Aleksandra
AU  - Petrović-Stanojević, Nataša
AU  - Mitić-Milikić, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Radojković, Dragica
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1633
AB  - Aim: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early-onset emphysema. Despite the relatively high prevalence of A1ATD, this condition is frequently underdiagnosed. Our aim was to determine the distribution of the A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian population. Methods: The study included the adults with chronic obstructive pulmonary disease (COPD) (n = 348), asthma (n = 71), and bronchiectasis (n = 35); the control was 1435 healthy blood donors. The A1ATD variants were identified by isoelectric focusing or polymerase chain reaction-mediated site-directed mutagenesis. Results: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers are associated with significantly higher risk of developing COPD than healthy individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8, and 1:1243) than in the Serbian population (1: 5519, 1: 38, and 1:5519). Conclusion: The high prevalence of A1ATD phenotypes/allele in our population has confirmed the necessity of screening for A1ATD in patients with COPD. On the other hand, on the basis of the estimated number of those with A1ATD among the COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the Serbian population.
PB  - Mary Ann Liebert Inc, New Rochelle
T2  - Genetic Testing and Molecular Biomarkers
T1  - Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases
VL  - 16
IS  - 11
SP  - 1282
EP  - 1286
DO  - 10.1089/gtmb.2012.0152
ER  - 

@article{
author = "Topić, Aleksandra and Stankovic, Marija and Divac-Rankov, Aleksandra and Petrović-Stanojević, Nataša and Mitić-Milikić, Marija and Nagorni-Obradović, Ljudmila and Radojković, Dragica",
year = "2012",
abstract = "Aim: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early-onset emphysema. Despite the relatively high prevalence of A1ATD, this condition is frequently underdiagnosed. Our aim was to determine the distribution of the A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian population. Methods: The study included the adults with chronic obstructive pulmonary disease (COPD) (n = 348), asthma (n = 71), and bronchiectasis (n = 35); the control was 1435 healthy blood donors. The A1ATD variants were identified by isoelectric focusing or polymerase chain reaction-mediated site-directed mutagenesis. Results: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers are associated with significantly higher risk of developing COPD than healthy individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8, and 1:1243) than in the Serbian population (1: 5519, 1: 38, and 1:5519). Conclusion: The high prevalence of A1ATD phenotypes/allele in our population has confirmed the necessity of screening for A1ATD in patients with COPD. On the other hand, on the basis of the estimated number of those with A1ATD among the COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the Serbian population.",
publisher = "Mary Ann Liebert Inc, New Rochelle",
journal = "Genetic Testing and Molecular Biomarkers",
title = "Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases",
volume = "16",
number = "11",
pages = "1282-1286",
doi = "10.1089/gtmb.2012.0152"
}

Topić, A., Stankovic, M., Divac-Rankov, A., Petrović-Stanojević, N., Mitić-Milikić, M., Nagorni-Obradović, L.,& Radojković, D.. (2012). Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases. in Genetic Testing and Molecular Biomarkers
Mary Ann Liebert Inc, New Rochelle., 16(11), 1282-1286.
https://doi.org/10.1089/gtmb.2012.0152

Topić A, Stankovic M, Divac-Rankov A, Petrović-Stanojević N, Mitić-Milikić M, Nagorni-Obradović L, Radojković D. Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases. in Genetic Testing and Molecular Biomarkers. 2012;16(11):1282-1286.
doi:10.1089/gtmb.2012.0152 .

Topić, Aleksandra, Stankovic, Marija, Divac-Rankov, Aleksandra, Petrović-Stanojević, Nataša, Mitić-Milikić, Marija, Nagorni-Obradović, Ljudmila, Radojković, Dragica, "Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases" in Genetic Testing and Molecular Biomarkers, 16, no. 11 (2012):1282-1286,
https://doi.org/10.1089/gtmb.2012.0152 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Ljujić, Mila
AU  - Radojković, Dragica
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1659
AB  - Context: Alpha-1-antitrypsin (A1AT) is the most abundant liver-derived, highly polymorphic, glycoprotein in plasma. Hereditary deficiency of alpha-1-antitrypsin in plasma (A1ATD) is a consequence of accumulation of polymers of A1AT mutants in endoplasmic reticulum of hepatocytes and other A1AT-producing cells. One of the clinical manifestations of A1ATD is liver disease in childhood and cirrhosis and/or hepatocellular carcinoma (HCC) in adulthood. Epidemiology and pathophysiology of liver failure in early childhood caused by A1ATD are well known, but the association with hepatocellular carcinoma is not clarified. The aim of this article is to review different aspects of association between A1AT variants and hepatocellular carcinoma, with emphasis on the epidemiology and molecular pathogenesis. The significance of A1AT as a biomarker in the diagnosis of HCC is also discussed. Evidence Acquisitions: Search for relevant articles were performed through Pub Med, HighWire, and Science Direct using the keywords "alpha-1-antitrypsin", "liver diseases", "hepatocellular carcinoma", "SERPINA1". Articles published until 2011 were reviewed. Results: Epidemiology studies revealed that severe A1ATD is a significant risk factor for cirrhosis and HCC unrelated to the presence of HBV or HCV infections. However, predisposition to HCC in moderate A1ATD is rare, and probably happens in combination with HBV and/or HCV infections or other unknown risk factors. It is assumed that accumulation of polymers of A1ATD variants in endoplasmic reticulum of hepatocytes leads to damage of hepatocytes by gain-of-function mechanism. Also, increased level of A1AT was recognized as diagnostic and prognostic marker of HCC. Conclusions: Clarification of a carcinogenic role for A1ATD and identification of pro-inflammatory or some still unknown factors that lead to increased susceptibility to HCC associated with A1ATD may contribute to a better understanding of hepatic carcinogenesis and to the development of new drugs.
PB  - Kowsar Publ, Hoensbroek
T2  - Hepatitis Monthly
T1  - Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma
VL  - 12
IS  - 10
DO  - 10.5812/hepatmon.7042
ER  - 

@article{
author = "Topić, Aleksandra and Ljujić, Mila and Radojković, Dragica",
year = "2012",
abstract = "Context: Alpha-1-antitrypsin (A1AT) is the most abundant liver-derived, highly polymorphic, glycoprotein in plasma. Hereditary deficiency of alpha-1-antitrypsin in plasma (A1ATD) is a consequence of accumulation of polymers of A1AT mutants in endoplasmic reticulum of hepatocytes and other A1AT-producing cells. One of the clinical manifestations of A1ATD is liver disease in childhood and cirrhosis and/or hepatocellular carcinoma (HCC) in adulthood. Epidemiology and pathophysiology of liver failure in early childhood caused by A1ATD are well known, but the association with hepatocellular carcinoma is not clarified. The aim of this article is to review different aspects of association between A1AT variants and hepatocellular carcinoma, with emphasis on the epidemiology and molecular pathogenesis. The significance of A1AT as a biomarker in the diagnosis of HCC is also discussed. Evidence Acquisitions: Search for relevant articles were performed through Pub Med, HighWire, and Science Direct using the keywords "alpha-1-antitrypsin", "liver diseases", "hepatocellular carcinoma", "SERPINA1". Articles published until 2011 were reviewed. Results: Epidemiology studies revealed that severe A1ATD is a significant risk factor for cirrhosis and HCC unrelated to the presence of HBV or HCV infections. However, predisposition to HCC in moderate A1ATD is rare, and probably happens in combination with HBV and/or HCV infections or other unknown risk factors. It is assumed that accumulation of polymers of A1ATD variants in endoplasmic reticulum of hepatocytes leads to damage of hepatocytes by gain-of-function mechanism. Also, increased level of A1AT was recognized as diagnostic and prognostic marker of HCC. Conclusions: Clarification of a carcinogenic role for A1ATD and identification of pro-inflammatory or some still unknown factors that lead to increased susceptibility to HCC associated with A1ATD may contribute to a better understanding of hepatic carcinogenesis and to the development of new drugs.",
publisher = "Kowsar Publ, Hoensbroek",
journal = "Hepatitis Monthly",
title = "Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma",
volume = "12",
number = "10",
doi = "10.5812/hepatmon.7042"
}

Topić, A., Ljujić, M.,& Radojković, D.. (2012). Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma. in Hepatitis Monthly
Kowsar Publ, Hoensbroek., 12(10).
https://doi.org/10.5812/hepatmon.7042

Topić A, Ljujić M, Radojković D. Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma. in Hepatitis Monthly. 2012;12(10).
doi:10.5812/hepatmon.7042 .

Topić, Aleksandra, Ljujić, Mila, Radojković, Dragica, "Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma" in Hepatitis Monthly, 12, no. 10 (2012),
https://doi.org/10.5812/hepatmon.7042 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Ljujić, Mila
AU  - Petrović-Stanojević, Nataša
AU  - Dopuđa-Pantić, Vesna
AU  - Radojković, Dragica
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1508
AB  - Propose: Alpha-1-antitrypsin (AAT) as the major circulating inhibitor of proteases has important role in protease-antiprotease homeostasis. Recent studies have confirmed its antiapoptotic role. AAT is a highly polymorphic protein. Individuals with normal variants have normal serum levels and functional activity of ATT. However, individuals with hereditary AAT deficiency (AATD) have low circulating levels of AAT. Severe AATD was identified as genetic risk factor for early onset of pulmonary emphysema. Association between AAT phenotypes and lung cancer (LC) is not clear; and different studies show contradictory results. The aim of this case-control study was to investigate phenotypes and serum level of AAT in LC. Methods: The study group included 147 patients with LC, classified as small cell lung cancer (SCLC, n=42) and non-small cell lung cancer (NSCLC, n=105). The control group consisted of 273 healthy blood donors. AAT phenotyping was performed by isoelectric-focusing and AAT concentration was measured using nephelometry. Results: There were no differences in the frequencies of AAT phenotypes and alleles between the control group and LC patients, as well as between NSCLC and SCLC groups. An elevated level of AAT was obtained in LC patients. PiMZ and PiMS phenotypes in LC patients were not deficient in the classical sense. AAT levels were 90 and 134%, respectively, when compared to PiMM phenotype in the control group. Conclusion: Our findings revealed that moderate deficiency of AAT is not risk factor for LC development. Although polymorphism of AAT was not associated with risk of LC, further research of this antiprotease and antiapoptotic protein could clarify its role in carcinogenesis, given its high concentration in LC patients, even in AATD patients.
PB  - Balkan Union of Oncology (B.U.ON.)
T2  - Journal of BUON
T1  - Phenotypes and serum level of alpha-1-antitrypsin in lung cancer
VL  - 16
IS  - 4
SP  - 672
EP  - 676
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1508
ER  - 

@article{
author = "Topić, Aleksandra and Ljujić, Mila and Petrović-Stanojević, Nataša and Dopuđa-Pantić, Vesna and Radojković, Dragica",
year = "2011",
abstract = "Propose: Alpha-1-antitrypsin (AAT) as the major circulating inhibitor of proteases has important role in protease-antiprotease homeostasis. Recent studies have confirmed its antiapoptotic role. AAT is a highly polymorphic protein. Individuals with normal variants have normal serum levels and functional activity of ATT. However, individuals with hereditary AAT deficiency (AATD) have low circulating levels of AAT. Severe AATD was identified as genetic risk factor for early onset of pulmonary emphysema. Association between AAT phenotypes and lung cancer (LC) is not clear; and different studies show contradictory results. The aim of this case-control study was to investigate phenotypes and serum level of AAT in LC. Methods: The study group included 147 patients with LC, classified as small cell lung cancer (SCLC, n=42) and non-small cell lung cancer (NSCLC, n=105). The control group consisted of 273 healthy blood donors. AAT phenotyping was performed by isoelectric-focusing and AAT concentration was measured using nephelometry. Results: There were no differences in the frequencies of AAT phenotypes and alleles between the control group and LC patients, as well as between NSCLC and SCLC groups. An elevated level of AAT was obtained in LC patients. PiMZ and PiMS phenotypes in LC patients were not deficient in the classical sense. AAT levels were 90 and 134%, respectively, when compared to PiMM phenotype in the control group. Conclusion: Our findings revealed that moderate deficiency of AAT is not risk factor for LC development. Although polymorphism of AAT was not associated with risk of LC, further research of this antiprotease and antiapoptotic protein could clarify its role in carcinogenesis, given its high concentration in LC patients, even in AATD patients.",
publisher = "Balkan Union of Oncology (B.U.ON.)",
journal = "Journal of BUON",
title = "Phenotypes and serum level of alpha-1-antitrypsin in lung cancer",
volume = "16",
number = "4",
pages = "672-676",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1508"
}

Topić, A., Ljujić, M., Petrović-Stanojević, N., Dopuđa-Pantić, V.,& Radojković, D.. (2011). Phenotypes and serum level of alpha-1-antitrypsin in lung cancer. in Journal of BUON
Balkan Union of Oncology (B.U.ON.)., 16(4), 672-676.
https://hdl.handle.net/21.15107/rcub_farfar_1508

Topić A, Ljujić M, Petrović-Stanojević N, Dopuđa-Pantić V, Radojković D. Phenotypes and serum level of alpha-1-antitrypsin in lung cancer. in Journal of BUON. 2011;16(4):672-676.
https://hdl.handle.net/21.15107/rcub_farfar_1508 .

Topić, Aleksandra, Ljujić, Mila, Petrović-Stanojević, Nataša, Dopuđa-Pantić, Vesna, Radojković, Dragica, "Phenotypes and serum level of alpha-1-antitrypsin in lung cancer" in Journal of BUON, 16, no. 4 (2011):672-676,
https://hdl.handle.net/21.15107/rcub_farfar_1508 .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Prokic, Dragan
AU  - Stankovic, Ivica
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1481
AB  - Alpha-1-antitrypsin deficiency (AATD), which predisposes liver disease in children, is often undiagnosed. Isoelectric focusing in 161 infants with liver dysfunction revealed 14.7% severe and 12.2% moderate AATD. Positive PAS-D and immunohistochemical staining was found in 60% of severe AATD, but in moderate AATD, only immunohistochemistry was positive in 100%. Bilirubinostasis, hepatomegaly, splenomegaly, cholestasis, hepatomegaly associated with cholestasis, acholia, high transaminases, and low birthweight were significantly more frequent in severe than in moderate AATD. Both AATDs showed significant portal inflammation, hepatic fibrosis, and viral infection. Early screening in children with liver dysfunction can contribute to the successful detection of AATD.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Fetal and Pediatric Pathology
T1  - Alpha-1-Antitrypsin Deficiency in Early Childhood
VL  - 30
IS  - 5
SP  - 312
EP  - 319
DO  - 10.3109/15513815.2011.572961
ER  - 

@article{
author = "Topić, Aleksandra and Prokic, Dragan and Stankovic, Ivica",
year = "2011",
abstract = "Alpha-1-antitrypsin deficiency (AATD), which predisposes liver disease in children, is often undiagnosed. Isoelectric focusing in 161 infants with liver dysfunction revealed 14.7% severe and 12.2% moderate AATD. Positive PAS-D and immunohistochemical staining was found in 60% of severe AATD, but in moderate AATD, only immunohistochemistry was positive in 100%. Bilirubinostasis, hepatomegaly, splenomegaly, cholestasis, hepatomegaly associated with cholestasis, acholia, high transaminases, and low birthweight were significantly more frequent in severe than in moderate AATD. Both AATDs showed significant portal inflammation, hepatic fibrosis, and viral infection. Early screening in children with liver dysfunction can contribute to the successful detection of AATD.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Fetal and Pediatric Pathology",
title = "Alpha-1-Antitrypsin Deficiency in Early Childhood",
volume = "30",
number = "5",
pages = "312-319",
doi = "10.3109/15513815.2011.572961"
}

Topić, A., Prokic, D.,& Stankovic, I.. (2011). Alpha-1-Antitrypsin Deficiency in Early Childhood. in Fetal and Pediatric Pathology
Taylor & Francis Inc, Philadelphia., 30(5), 312-319.
https://doi.org/10.3109/15513815.2011.572961

Topić A, Prokic D, Stankovic I. Alpha-1-Antitrypsin Deficiency in Early Childhood. in Fetal and Pediatric Pathology. 2011;30(5):312-319.
doi:10.3109/15513815.2011.572961 .

Topić, Aleksandra, Prokic, Dragan, Stankovic, Ivica, "Alpha-1-Antitrypsin Deficiency in Early Childhood" in Fetal and Pediatric Pathology, 30, no. 5 (2011):312-319,
https://doi.org/10.3109/15513815.2011.572961 . .