TY  - JOUR
AU  - Milaković, Dragana
AU  - Kovačević, Tijana
AU  - Kovačević, Peđa
AU  - Barišić, Vedrana
AU  - Avram, Sanja
AU  - Dragić, Saša
AU  - Zlojutro, Biljana
AU  - Momčičević, Danica
AU  - Miljković, Branislava
AU  - Vučićević, Katarina
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5557
AB  - During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients’ individual PK parameters and corresponding concentration–time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC24/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.
PB  - MDPI
T2  - Pharmaceutics
T1  - Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing
VL  - 16
IS  - 2
DO  - 10.3390/pharmaceutics16020253
ER  - 

@article{
author = "Milaković, Dragana and Kovačević, Tijana and Kovačević, Peđa and Barišić, Vedrana and Avram, Sanja and Dragić, Saša and Zlojutro, Biljana and Momčičević, Danica and Miljković, Branislava and Vučićević, Katarina",
year = "2024",
abstract = "During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients’ individual PK parameters and corresponding concentration–time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC24/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing",
volume = "16",
number = "2",
doi = "10.3390/pharmaceutics16020253"
}

Milaković, D., Kovačević, T., Kovačević, P., Barišić, V., Avram, S., Dragić, S., Zlojutro, B., Momčičević, D., Miljković, B.,& Vučićević, K.. (2024). Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing. in Pharmaceutics
MDPI., 16(2).
https://doi.org/10.3390/pharmaceutics16020253

Milaković D, Kovačević T, Kovačević P, Barišić V, Avram S, Dragić S, Zlojutro B, Momčičević D, Miljković B, Vučićević K. Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing. in Pharmaceutics. 2024;16(2).
doi:10.3390/pharmaceutics16020253 .

Milaković, Dragana, Kovačević, Tijana, Kovačević, Peđa, Barišić, Vedrana, Avram, Sanja, Dragić, Saša, Zlojutro, Biljana, Momčičević, Danica, Miljković, Branislava, Vučićević, Katarina, "Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation—A Step toward Correct Dosing" in Pharmaceutics, 16, no. 2 (2024),
https://doi.org/10.3390/pharmaceutics16020253 . .

TY  - JOUR
AU  - Mirjanić-Azarić, Bosa
AU  - Milinković, Neda
AU  - Bogavac-Stanojević, Nataša
AU  - Avram, Sanja
AU  - Stojaković-Jelisavac, Tanja
AU  - Stojanović, Darja
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4173
AB  - Background: The aim of this study was to determine the reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and FT3/FT4 ratio using indirect methods. Methods: We analyzed 1256 results TSH, FT4 and FT3 collected from a laboratory information system between 2017 and 2021. All measurements were performed on a Siemens ADVIA Centaur XP analyzer using the chemiluminescent immunoassay. We calculated the values of the 2.5th and 97.5th percentiles as recommended by the IFCC (CLSI C28-A3). Results: The RIs derived for TSH, FT4, FT3 and FT3/FT4 ratio were 0.34–4.10 mIU/L, 11.3–20.6 pmol/L, 3.5–6.32 pmol/L and 0.21–0.47, respectively. We found a significant difference between calculated RIs for the TSH and FT4 and those recommended by the manufacturer. Also, FT3 values were significantly higher in the group younger than 30 years relative to the fourth decade (5.26 vs. 5.02, p=0.005), the fifth decade (5.26 vs. 4.94, p=0.001), the sixth decade (5.26 vs. 4.87, p<0.001), the seventh decade (5.26 vs. 4.79, p<0.001) and the group older than 70 years old (5.26 vs. 4.55, p<0.001). Likewise, we found for TSH values and FT3/FT4 ratio a significant difference (p <0.001) between different age groups. Conclusions: The establishing RIs for the population of the Republic of Srpska were significantly differed from the recommended RIs by the manufacturer for TSH and FT4. Our results encourage other laboratories to develop their own RIs for thyroid parameters by applying CLSI recommendations.
AB  - Uvod: Cilj ove studije bio je da se odrede referentni intervali (RI) tireotropnog hormona (TSH), slobodnog tiroksina (FT4), slobodnog trijodotironina (FT3) i odnosa FT3/FT4 indirektnom metodom procene referentnih intervala. Metode: Analizirali smo 1256 dobijenih vrednosti TSH, FT4 i FT3 u periodu između 2017. i 2021. godine. Rezultate smo uzeli iz laboratorijskog informacionog sistema. Sva merenja su izvedena na Siemens ADVIA Centaur XP analizatoru pomo}u hemiluminiscentnih imunohemijskih testova. Izračunali smo vrednosti 2,5-og i 97,5-og percentila prema preporuci IFCC-a (CLSI C28-A3). Rezultati: Procenjeni RI za TSH, FT4, FT3 i odnos FT3/FT4 bili su 0,34-4,10 mIU/L; 11,3-20,6 pmol/L; 3,5-6,32 pmol/L i 0,21-0,47. Utvrdili smo značajnu razliku između izračunatih RI za TSH i FT4 i onih koje preporučuje proizvođač. Takođe, vrednosti FT3 bile su značajno ve}e u grupi mlađoj od 30 godina u odnosu na četvrtu deceniju (5,26 vs. 5,02; p = 0,005), petu deceniju (5,26 vs. 4,94; p = 0,001), šestu deceniju (5,26 vs. 4,87; p<0,001), sedmu deceniju (5,26 vs. 4,79; p<0,001) i grupu stariju od 70 godina (5,26 vs. 4,55; p<0,001). Isto tako, za vrednosti TSH i odnos FT3/FT4 pronašli smo značajnu razliku (p <0,001) između različitih dobnih grupa. Zaključak: Procenjene vrednosti referentnih intervala za TSH i FT4 za stanovništvo Republike Srpske značajno su se razlikovale od preporučenih RI od strane proizvođača. Naši rezultati podstiču druge laboratorije da izrade sopstvene RI za parametre štitne žlezde primenom CLSI preporuka.
PB  - Society of Medical Biochemists of Serbia
T2  - Journal of Medical Biochemistry
T1  - Indirect estimation of reference intervals for thyroid parameters using advia centaur XP analyzer
T1  - Indirektna procjena referentnih intervala za parametre štitne žlijezde upotrebom advia centaur XP analizatora
VL  - 41
IS  - 2
SP  - 238
EP  - 245
DO  - 10.5937/jomb0-33543
ER  - 

@article{
author = "Mirjanić-Azarić, Bosa and Milinković, Neda and Bogavac-Stanojević, Nataša and Avram, Sanja and Stojaković-Jelisavac, Tanja and Stojanović, Darja",
year = "2022",
abstract = "Background: The aim of this study was to determine the reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and FT3/FT4 ratio using indirect methods. Methods: We analyzed 1256 results TSH, FT4 and FT3 collected from a laboratory information system between 2017 and 2021. All measurements were performed on a Siemens ADVIA Centaur XP analyzer using the chemiluminescent immunoassay. We calculated the values of the 2.5th and 97.5th percentiles as recommended by the IFCC (CLSI C28-A3). Results: The RIs derived for TSH, FT4, FT3 and FT3/FT4 ratio were 0.34–4.10 mIU/L, 11.3–20.6 pmol/L, 3.5–6.32 pmol/L and 0.21–0.47, respectively. We found a significant difference between calculated RIs for the TSH and FT4 and those recommended by the manufacturer. Also, FT3 values were significantly higher in the group younger than 30 years relative to the fourth decade (5.26 vs. 5.02, p=0.005), the fifth decade (5.26 vs. 4.94, p=0.001), the sixth decade (5.26 vs. 4.87, p<0.001), the seventh decade (5.26 vs. 4.79, p<0.001) and the group older than 70 years old (5.26 vs. 4.55, p<0.001). Likewise, we found for TSH values and FT3/FT4 ratio a significant difference (p <0.001) between different age groups. Conclusions: The establishing RIs for the population of the Republic of Srpska were significantly differed from the recommended RIs by the manufacturer for TSH and FT4. Our results encourage other laboratories to develop their own RIs for thyroid parameters by applying CLSI recommendations., Uvod: Cilj ove studije bio je da se odrede referentni intervali (RI) tireotropnog hormona (TSH), slobodnog tiroksina (FT4), slobodnog trijodotironina (FT3) i odnosa FT3/FT4 indirektnom metodom procene referentnih intervala. Metode: Analizirali smo 1256 dobijenih vrednosti TSH, FT4 i FT3 u periodu između 2017. i 2021. godine. Rezultate smo uzeli iz laboratorijskog informacionog sistema. Sva merenja su izvedena na Siemens ADVIA Centaur XP analizatoru pomo}u hemiluminiscentnih imunohemijskih testova. Izračunali smo vrednosti 2,5-og i 97,5-og percentila prema preporuci IFCC-a (CLSI C28-A3). Rezultati: Procenjeni RI za TSH, FT4, FT3 i odnos FT3/FT4 bili su 0,34-4,10 mIU/L; 11,3-20,6 pmol/L; 3,5-6,32 pmol/L i 0,21-0,47. Utvrdili smo značajnu razliku između izračunatih RI za TSH i FT4 i onih koje preporučuje proizvođač. Takođe, vrednosti FT3 bile su značajno ve}e u grupi mlađoj od 30 godina u odnosu na četvrtu deceniju (5,26 vs. 5,02; p = 0,005), petu deceniju (5,26 vs. 4,94; p = 0,001), šestu deceniju (5,26 vs. 4,87; p<0,001), sedmu deceniju (5,26 vs. 4,79; p<0,001) i grupu stariju od 70 godina (5,26 vs. 4,55; p<0,001). Isto tako, za vrednosti TSH i odnos FT3/FT4 pronašli smo značajnu razliku (p <0,001) između različitih dobnih grupa. Zaključak: Procenjene vrednosti referentnih intervala za TSH i FT4 za stanovništvo Republike Srpske značajno su se razlikovale od preporučenih RI od strane proizvođača. Naši rezultati podstiču druge laboratorije da izrade sopstvene RI za parametre štitne žlezde primenom CLSI preporuka.",
publisher = "Society of Medical Biochemists of Serbia",
journal = "Journal of Medical Biochemistry",
title = "Indirect estimation of reference intervals for thyroid parameters using advia centaur XP analyzer, Indirektna procjena referentnih intervala za parametre štitne žlijezde upotrebom advia centaur XP analizatora",
volume = "41",
number = "2",
pages = "238-245",
doi = "10.5937/jomb0-33543"
}

Mirjanić-Azarić, B., Milinković, N., Bogavac-Stanojević, N., Avram, S., Stojaković-Jelisavac, T.,& Stojanović, D.. (2022). Indirect estimation of reference intervals for thyroid parameters using advia centaur XP analyzer. in Journal of Medical Biochemistry
Society of Medical Biochemists of Serbia., 41(2), 238-245.
https://doi.org/10.5937/jomb0-33543

Mirjanić-Azarić B, Milinković N, Bogavac-Stanojević N, Avram S, Stojaković-Jelisavac T, Stojanović D. Indirect estimation of reference intervals for thyroid parameters using advia centaur XP analyzer. in Journal of Medical Biochemistry. 2022;41(2):238-245.
doi:10.5937/jomb0-33543 .

Mirjanić-Azarić, Bosa, Milinković, Neda, Bogavac-Stanojević, Nataša, Avram, Sanja, Stojaković-Jelisavac, Tanja, Stojanović, Darja, "Indirect estimation of reference intervals for thyroid parameters using advia centaur XP analyzer" in Journal of Medical Biochemistry, 41, no. 2 (2022):238-245,
https://doi.org/10.5937/jomb0-33543 . .

TY  - JOUR
AU  - Kovačević, Tijana
AU  - Miljković, Branislava
AU  - Kovačević, Peđa
AU  - Dragić, Saša
AU  - Momčićević, Danica
AU  - Avram, Sanja
AU  - Jovanović, Marija
AU  - Vučićević, Katarina
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4826
AB  - Purpose: The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired renal function.

Materials and methods: A prospective analysis of 146 concentrations from 73 adult critically ill septic patients treated with 1-h intravenous infusion of vancomycin were included in the study. A nonlinear mixed effects modeling (NONMEM) approach was applied for data analysis and evaluation of the final model. The influence of creatinine clearance calculated by the Cockcroft-Gault equation (CrCl), and other potential covariates on vancomycin clearance (CL) were evaluated.

Results: The final one-compartment pharmacokinetic model includes the effect of CrCl on CL. Population pharmacokinetic values for a typical subject were estimated at 0.024 l/h for CL dependent on renal function (CLCrCl), 1.93 l/h for residual portion of CL (not dependent on renal function), and 0.511 l/kg for volume of distribution (V). According to the final model, for patients with CrCl = 120 ml/min, the median vancomycin total CL is 4.81 l/h, while CrCl-dependent fraction accounts for approximately 60% of CL.

Conclusions: The developed population vancomycin model may be used in estimating individual CL for adult critically ill septic patients, and could be applied for individualizing dosage regimens taking into account the continuous effect of CrCl.
PB  - Elsevier Inc.
T2  - Journal of Critical Care
T1  - Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients
VL  - 55
SP  - 116
EP  - 121
DO  - 10.1016/j.jcrc.2019.10.012
ER  - 

@article{
author = "Kovačević, Tijana and Miljković, Branislava and Kovačević, Peđa and Dragić, Saša and Momčićević, Danica and Avram, Sanja and Jovanović, Marija and Vučićević, Katarina",
year = "2020",
abstract = "Purpose: The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired renal function.

Materials and methods: A prospective analysis of 146 concentrations from 73 adult critically ill septic patients treated with 1-h intravenous infusion of vancomycin were included in the study. A nonlinear mixed effects modeling (NONMEM) approach was applied for data analysis and evaluation of the final model. The influence of creatinine clearance calculated by the Cockcroft-Gault equation (CrCl), and other potential covariates on vancomycin clearance (CL) were evaluated.

Results: The final one-compartment pharmacokinetic model includes the effect of CrCl on CL. Population pharmacokinetic values for a typical subject were estimated at 0.024 l/h for CL dependent on renal function (CLCrCl), 1.93 l/h for residual portion of CL (not dependent on renal function), and 0.511 l/kg for volume of distribution (V). According to the final model, for patients with CrCl = 120 ml/min, the median vancomycin total CL is 4.81 l/h, while CrCl-dependent fraction accounts for approximately 60% of CL.

Conclusions: The developed population vancomycin model may be used in estimating individual CL for adult critically ill septic patients, and could be applied for individualizing dosage regimens taking into account the continuous effect of CrCl.",
publisher = "Elsevier Inc.",
journal = "Journal of Critical Care",
title = "Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients",
volume = "55",
pages = "116-121",
doi = "10.1016/j.jcrc.2019.10.012"
}

Kovačević, T., Miljković, B., Kovačević, P., Dragić, S., Momčićević, D., Avram, S., Jovanović, M.,& Vučićević, K.. (2020). Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. in Journal of Critical Care
Elsevier Inc.., 55, 116-121.
https://doi.org/10.1016/j.jcrc.2019.10.012

Kovačević T, Miljković B, Kovačević P, Dragić S, Momčićević D, Avram S, Jovanović M, Vučićević K. Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients. in Journal of Critical Care. 2020;55:116-121.
doi:10.1016/j.jcrc.2019.10.012 .

Kovačević, Tijana, Miljković, Branislava, Kovačević, Peđa, Dragić, Saša, Momčićević, Danica, Avram, Sanja, Jovanović, Marija, Vučićević, Katarina, "Population pharmacokinetic model of Vancomycin based on therapeutic drug monitoring data in critically ill septic patients" in Journal of Critical Care, 55 (2020):116-121,
https://doi.org/10.1016/j.jcrc.2019.10.012 . .

TY  - JOUR
AU  - Mirjanić-Azarić, Bosa
AU  - Avram, Sanja
AU  - Stojaković-Jelisavac, Tanja
AU  - Stojanović, Darja
AU  - Petković, Mira
AU  - Bogavac-Stanojević, Nataša
AU  - Ignjatović, Svetlana
AU  - Stojanov, Marina
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3008
AB  - Background: The aim of this study was to determine the reference values for thyrotropin (TSH), thyroid hormones (total and free thyroxine, T4 and fT4; total and free triiodothyronine, T3 and fT3), thyroglobulin (Tg) and thyroid antibodies (thyroid peroxidase, TPOAb and thyroglobulin antibody, TgAb) in the population of the Republic of Srpska. Methods: A total of 250 euthyroid subjects were enrolled in this study. A direct method for choosing reference subjects was used to establish reference intervals. The hormones and thyroid antibodies were measured by an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics, Mannheim, Germany). We calculated the re f erence intervals by MedCalc, version 12.1.4.0 (MedCalc software, Belgium) as recommended by the IFCC (CLSI C28-A3). Results: Using guidelines recommended by the National Academy of Clinical Biochemistry (NACB) and based on standard statistical approaches, the reference intervals derived for TSH, fT4, T4, fT3, T3 were 0.75-5.32 mIU/L, 12.29-20.03 pmol/L, 73.49-126,30 nmol/L, 4.11-6.32 pmol/L, 1.15-2.32 nmol/L and for Tg, TPOAb, TgAb were 3.63-26.00 mu g/L,  lt  18.02 mIU/L,  lt  98.00 mIU/L, respe ctively. We found a significant difference (p lt  0.05) in TSH and fT3 values between different age groups as well as in T4, fT4 and fT3 values between ge nder groups. Conclusions: The established reference values for the population of the Republic of Srpska were significantly different from the values recommended by the manufacturer of reagents (Roche Diagnostics). Our results showed that a laboratory needs to establish its own reference values in order to set up a proper diagnosis, as well as to treat patients successfully.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Direct Estimation of Reference Intervals for Thyroid Parameters in the Republic of Srpska
VL  - 36
IS  - 2
SP  - 137
EP  - 144
DO  - 10.1515/jomb-2017-0008
ER  - 

@article{
author = "Mirjanić-Azarić, Bosa and Avram, Sanja and Stojaković-Jelisavac, Tanja and Stojanović, Darja and Petković, Mira and Bogavac-Stanojević, Nataša and Ignjatović, Svetlana and Stojanov, Marina",
year = "2017",
abstract = "Background: The aim of this study was to determine the reference values for thyrotropin (TSH), thyroid hormones (total and free thyroxine, T4 and fT4; total and free triiodothyronine, T3 and fT3), thyroglobulin (Tg) and thyroid antibodies (thyroid peroxidase, TPOAb and thyroglobulin antibody, TgAb) in the population of the Republic of Srpska. Methods: A total of 250 euthyroid subjects were enrolled in this study. A direct method for choosing reference subjects was used to establish reference intervals. The hormones and thyroid antibodies were measured by an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics, Mannheim, Germany). We calculated the re f erence intervals by MedCalc, version 12.1.4.0 (MedCalc software, Belgium) as recommended by the IFCC (CLSI C28-A3). Results: Using guidelines recommended by the National Academy of Clinical Biochemistry (NACB) and based on standard statistical approaches, the reference intervals derived for TSH, fT4, T4, fT3, T3 were 0.75-5.32 mIU/L, 12.29-20.03 pmol/L, 73.49-126,30 nmol/L, 4.11-6.32 pmol/L, 1.15-2.32 nmol/L and for Tg, TPOAb, TgAb were 3.63-26.00 mu g/L,  lt  18.02 mIU/L,  lt  98.00 mIU/L, respe ctively. We found a significant difference (p lt  0.05) in TSH and fT3 values between different age groups as well as in T4, fT4 and fT3 values between ge nder groups. Conclusions: The established reference values for the population of the Republic of Srpska were significantly different from the values recommended by the manufacturer of reagents (Roche Diagnostics). Our results showed that a laboratory needs to establish its own reference values in order to set up a proper diagnosis, as well as to treat patients successfully.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Direct Estimation of Reference Intervals for Thyroid Parameters in the Republic of Srpska",
volume = "36",
number = "2",
pages = "137-144",
doi = "10.1515/jomb-2017-0008"
}

Mirjanić-Azarić, B., Avram, S., Stojaković-Jelisavac, T., Stojanović, D., Petković, M., Bogavac-Stanojević, N., Ignjatović, S.,& Stojanov, M.. (2017). Direct Estimation of Reference Intervals for Thyroid Parameters in the Republic of Srpska. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 36(2), 137-144.
https://doi.org/10.1515/jomb-2017-0008

Mirjanić-Azarić B, Avram S, Stojaković-Jelisavac T, Stojanović D, Petković M, Bogavac-Stanojević N, Ignjatović S, Stojanov M. Direct Estimation of Reference Intervals for Thyroid Parameters in the Republic of Srpska. in Journal of Medical Biochemistry. 2017;36(2):137-144.
doi:10.1515/jomb-2017-0008 .

Mirjanić-Azarić, Bosa, Avram, Sanja, Stojaković-Jelisavac, Tanja, Stojanović, Darja, Petković, Mira, Bogavac-Stanojević, Nataša, Ignjatović, Svetlana, Stojanov, Marina, "Direct Estimation of Reference Intervals for Thyroid Parameters in the Republic of Srpska" in Journal of Medical Biochemistry, 36, no. 2 (2017):137-144,
https://doi.org/10.1515/jomb-2017-0008 . .

TY  - JOUR
AU  - Mirjanić-Azarić, Bosa
AU  - Jelić-Ivanović, Zorana
AU  - Zeljković, Aleksandra
AU  - Vekić, Jelena
AU  - Juergens, Guenther
AU  - Milivojac, Tatjana
AU  - Avram, Sanja
AU  - Ćorić, Jozo
AU  - Marc, Janja
AU  - Černe, Darko
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2432
AB  - Background: High-density lipoproteins (HDL) have atheroprotective biological properties: antioxidative, anti-apoptotic, anti-inflammatory, and they have the efflux capacity of cellular cholesterol. Plasma mRNA analysis can be used to investigate statin pleiotropy in vivo as a new analytical tool for non-invasive assessment of gene expression in vascular beds. The aim of this study was to assess the pleiotropic effects of atorvastatin in stable angina patients with highrisk values (group A) as compared with patients who had borderline and desirable HDL-cholesterol (HDL-C) values (group B). Methods: The atorvastatin therapy (20 mg/day) was given to forty-three patients with stable angina for 10 weeks. We investigated three statin pleiotropy-targeted genes: intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2 and cathepsin S and assessed by gel electrophoresis gradient the effects of atorvastatin on HDL size and subclasses. Results: In group A, after therapy, HDL-C concentration was significantly increased but not in group B. Atorvastatin lowered plasma chemokine (C-C motif) ligand 2 and intercellular adhesion molecule-1 mRNA levels in both groups, but did not change the plasma cathepsin S mRNA levels. In group A only, baseline total bilirubin showed negative cor relations with the genes of cathepsin S (r=-0.506; p = 0.023) and significantly increased after therapy. Conclusions: HDL-C and bilirubin can be promising therapeutic targets in the treatment of cardiovascular diseases. Analysis of cell-free mRNA in plasma might become a useful tool for estimating statin pleiotropy.
AB  - Uvod: Lipoproteini velike gustine (HDL) imaju ateroprotektivne biološke osobine: antioksidativne, antiapoptotičke, antiinflamatorne kao i kapacitet da izvlače holesterol iz ćelija. Analiza plazmatske mRNA može da se koristi za ispitivanje plejotropnih efekata statina in vivo kao novo analitičko sredstvo za neinvazivnu procenu ekspresije gena u zidu krvnog suda. Cilj ove studije je bio da se procene plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom sa visokorizičnim vrednostima (grupa A) u odnosu na pacijente sa graničnim i poželjnim vrednostima HDL holesterola (HDLC) (grupa B). Metode: Četrdeset tri pacijenta sa stabilnom anginom su primala terapiju atorvastatinom (20 mg/dan) 10 nedelja. Mi smo ispitivali tri gena značajna za plejotropno delovanje statina: intracelularni adhezioni molekul-1, hemokin (C-C motiv) ligand 2 i katepsin S i procenjivali smo efekte atorvastatina na veličinu i raspodelu HDL subfrakcija pomoću elektroforeze na poliakrilamidnom gradijent gelu. Rezultati: U grupi A, posle terapije, HDL-C koncentracija se značajno povećala, ali ne i u grupi B. Atorvastatin je snizio plazmatski nivo hemokin (C-C motiv) liganda 2 i intracelularnog adhezionog molekula-1 mRNA u obe grupe, ali nije promenio plazmatski nivo gena za katepsin S. Samo u grupi A, ukupni bilirubin je pokazao negativnu korelaciju sa genom za katepsin S (r = -0,506; p = 0,023) pre započinjanja terapije i značajni porast nakon terapije atorvastatinom. Zaključak: HDL-C i bilirubin mogu biti obećavajući terapijski ciljevi u lečenju kardiovaskularnih bolesti. Analiza slobodne mRNA (eng. cell-free mRNA) u plazmi može postati korisno sredstvo za procenu plejotropnog delovanja statina.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA
T1  - Plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom - dokazi dobijeni analizom veličine i raspodele subfrakcija lipoproteina velike gustine i plazmatske mRNA
VL  - 34
IS  - 3
SP  - 314
EP  - 322
DO  - 10.2478/jomb-2014-0058
ER  - 

@article{
author = "Mirjanić-Azarić, Bosa and Jelić-Ivanović, Zorana and Zeljković, Aleksandra and Vekić, Jelena and Juergens, Guenther and Milivojac, Tatjana and Avram, Sanja and Ćorić, Jozo and Marc, Janja and Černe, Darko",
year = "2015",
abstract = "Background: High-density lipoproteins (HDL) have atheroprotective biological properties: antioxidative, anti-apoptotic, anti-inflammatory, and they have the efflux capacity of cellular cholesterol. Plasma mRNA analysis can be used to investigate statin pleiotropy in vivo as a new analytical tool for non-invasive assessment of gene expression in vascular beds. The aim of this study was to assess the pleiotropic effects of atorvastatin in stable angina patients with highrisk values (group A) as compared with patients who had borderline and desirable HDL-cholesterol (HDL-C) values (group B). Methods: The atorvastatin therapy (20 mg/day) was given to forty-three patients with stable angina for 10 weeks. We investigated three statin pleiotropy-targeted genes: intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2 and cathepsin S and assessed by gel electrophoresis gradient the effects of atorvastatin on HDL size and subclasses. Results: In group A, after therapy, HDL-C concentration was significantly increased but not in group B. Atorvastatin lowered plasma chemokine (C-C motif) ligand 2 and intercellular adhesion molecule-1 mRNA levels in both groups, but did not change the plasma cathepsin S mRNA levels. In group A only, baseline total bilirubin showed negative cor relations with the genes of cathepsin S (r=-0.506; p = 0.023) and significantly increased after therapy. Conclusions: HDL-C and bilirubin can be promising therapeutic targets in the treatment of cardiovascular diseases. Analysis of cell-free mRNA in plasma might become a useful tool for estimating statin pleiotropy., Uvod: Lipoproteini velike gustine (HDL) imaju ateroprotektivne biološke osobine: antioksidativne, antiapoptotičke, antiinflamatorne kao i kapacitet da izvlače holesterol iz ćelija. Analiza plazmatske mRNA može da se koristi za ispitivanje plejotropnih efekata statina in vivo kao novo analitičko sredstvo za neinvazivnu procenu ekspresije gena u zidu krvnog suda. Cilj ove studije je bio da se procene plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom sa visokorizičnim vrednostima (grupa A) u odnosu na pacijente sa graničnim i poželjnim vrednostima HDL holesterola (HDLC) (grupa B). Metode: Četrdeset tri pacijenta sa stabilnom anginom su primala terapiju atorvastatinom (20 mg/dan) 10 nedelja. Mi smo ispitivali tri gena značajna za plejotropno delovanje statina: intracelularni adhezioni molekul-1, hemokin (C-C motiv) ligand 2 i katepsin S i procenjivali smo efekte atorvastatina na veličinu i raspodelu HDL subfrakcija pomoću elektroforeze na poliakrilamidnom gradijent gelu. Rezultati: U grupi A, posle terapije, HDL-C koncentracija se značajno povećala, ali ne i u grupi B. Atorvastatin je snizio plazmatski nivo hemokin (C-C motiv) liganda 2 i intracelularnog adhezionog molekula-1 mRNA u obe grupe, ali nije promenio plazmatski nivo gena za katepsin S. Samo u grupi A, ukupni bilirubin je pokazao negativnu korelaciju sa genom za katepsin S (r = -0,506; p = 0,023) pre započinjanja terapije i značajni porast nakon terapije atorvastatinom. Zaključak: HDL-C i bilirubin mogu biti obećavajući terapijski ciljevi u lečenju kardiovaskularnih bolesti. Analiza slobodne mRNA (eng. cell-free mRNA) u plazmi može postati korisno sredstvo za procenu plejotropnog delovanja statina.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA, Plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom - dokazi dobijeni analizom veličine i raspodele subfrakcija lipoproteina velike gustine i plazmatske mRNA",
volume = "34",
number = "3",
pages = "314-322",
doi = "10.2478/jomb-2014-0058"
}

Mirjanić-Azarić, B., Jelić-Ivanović, Z., Zeljković, A., Vekić, J., Juergens, G., Milivojac, T., Avram, S., Ćorić, J., Marc, J.,& Černe, D.. (2015). The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 34(3), 314-322.
https://doi.org/10.2478/jomb-2014-0058

Mirjanić-Azarić B, Jelić-Ivanović Z, Zeljković A, Vekić J, Juergens G, Milivojac T, Avram S, Ćorić J, Marc J, Černe D. The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA. in Journal of Medical Biochemistry. 2015;34(3):314-322.
doi:10.2478/jomb-2014-0058 .

Mirjanić-Azarić, Bosa, Jelić-Ivanović, Zorana, Zeljković, Aleksandra, Vekić, Jelena, Juergens, Guenther, Milivojac, Tatjana, Avram, Sanja, Ćorić, Jozo, Marc, Janja, Černe, Darko, "The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA" in Journal of Medical Biochemistry, 34, no. 3 (2015):314-322,
https://doi.org/10.2478/jomb-2014-0058 . .