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  - 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  - Beletić, Anđelo
AU  - Mirković, Duško
AU  - Dudvarski-Ilić, Aleksandra
AU  - Milenković, Branislava
AU  - Nagorni-Obradović, Ljudmila
AU  - Đorđević, Valentina
AU  - Ignjatović, Svetlana
AU  - Majkić-Singh, Nada
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2299
AB  - Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B-12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B-12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age ((X) over bar +/- SD=49.0 +/- 14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B-12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and chi(2) tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B-12 were 4.13 (2.16) mu g/L and 463.6 (271.0) ng/L, whereas only vitamin B-12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B-12 deficiency differed significantly (P=0.000 and P lt 0.000 for folate and vitamin B12 respectively), depending on the cutoff used for classification (4.4, 6.6 and 8.0 mu g/L folate; 203 and 473 ng/L - vitamin B-12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B-12 deficiency. Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B-12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Questionable Reliability of Homocysteine As the Metabolic Marker for Folate and Vitamin B12 Deficiency in Patients with Chronic Obstructive Pulmonary Disease
VL  - 34
IS  - 4
SP  - 467
EP  - 472
DO  - 10.2478/jomb-2014-0046
ER  - 

@article{
author = "Beletić, Anđelo and Mirković, Duško and Dudvarski-Ilić, Aleksandra and Milenković, Branislava and Nagorni-Obradović, Ljudmila and Đorđević, Valentina and Ignjatović, Svetlana and Majkić-Singh, Nada",
year = "2015",
abstract = "Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B-12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B-12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age ((X) over bar +/- SD=49.0 +/- 14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B-12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and chi(2) tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B-12 were 4.13 (2.16) mu g/L and 463.6 (271.0) ng/L, whereas only vitamin B-12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B-12 deficiency differed significantly (P=0.000 and P lt 0.000 for folate and vitamin B12 respectively), depending on the cutoff used for classification (4.4, 6.6 and 8.0 mu g/L folate; 203 and 473 ng/L - vitamin B-12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B-12 deficiency. Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B-12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Questionable Reliability of Homocysteine As the Metabolic Marker for Folate and Vitamin B12 Deficiency in Patients with Chronic Obstructive Pulmonary Disease",
volume = "34",
number = "4",
pages = "467-472",
doi = "10.2478/jomb-2014-0046"
}

Beletić, A., Mirković, D., Dudvarski-Ilić, A., Milenković, B., Nagorni-Obradović, L., Đorđević, V., Ignjatović, S.,& Majkić-Singh, N.. (2015). Questionable Reliability of Homocysteine As the Metabolic Marker for Folate and Vitamin B12 Deficiency in Patients with Chronic Obstructive Pulmonary Disease. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 34(4), 467-472.
https://doi.org/10.2478/jomb-2014-0046

Beletić A, Mirković D, Dudvarski-Ilić A, Milenković B, Nagorni-Obradović L, Đorđević V, Ignjatović S, Majkić-Singh N. Questionable Reliability of Homocysteine As the Metabolic Marker for Folate and Vitamin B12 Deficiency in Patients with Chronic Obstructive Pulmonary Disease. in Journal of Medical Biochemistry. 2015;34(4):467-472.
doi:10.2478/jomb-2014-0046 .

Beletić, Anđelo, Mirković, Duško, Dudvarski-Ilić, Aleksandra, Milenković, Branislava, Nagorni-Obradović, Ljudmila, Đorđević, Valentina, Ignjatović, Svetlana, Majkić-Singh, Nada, "Questionable Reliability of Homocysteine As the Metabolic Marker for Folate and Vitamin B12 Deficiency in Patients with Chronic Obstructive Pulmonary Disease" in Journal of Medical Biochemistry, 34, no. 4 (2015):467-472,
https://doi.org/10.2478/jomb-2014-0046 . .

TY  - JOUR
AU  - Beletić, Anđelo
AU  - Dudvarski-Ilić, Aleksandra
AU  - Milenković, Branislava
AU  - Nagorni-Obradović, Ljudmila
AU  - Ljujić, Mila
AU  - Đorđević, Valentina
AU  - Mirković, Duško
AU  - Radojković, Dragica
AU  - Majkić-Singh, Nada
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2204
AB  - Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.
PB  - Croatian Soc Medical Biochemists, Zagreb
T2  - Biochemia Medica
T1  - Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?
VL  - 24
IS  - 2
SP  - 293
EP  - 298
DO  - 10.11613/BM.2014.032
ER  - 

@article{
author = "Beletić, Anđelo and Dudvarski-Ilić, Aleksandra and Milenković, Branislava and Nagorni-Obradović, Ljudmila and Ljujić, Mila and Đorđević, Valentina and Mirković, Duško and Radojković, Dragica and Majkić-Singh, Nada",
year = "2014",
abstract = "Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.",
publisher = "Croatian Soc Medical Biochemists, Zagreb",
journal = "Biochemia Medica",
title = "Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?",
volume = "24",
number = "2",
pages = "293-298",
doi = "10.11613/BM.2014.032"
}

Beletić, A., Dudvarski-Ilić, A., Milenković, B., Nagorni-Obradović, L., Ljujić, M., Đorđević, V., Mirković, D., Radojković, D.,& Majkić-Singh, N.. (2014). Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?. in Biochemia Medica
Croatian Soc Medical Biochemists, Zagreb., 24(2), 293-298.
https://doi.org/10.11613/BM.2014.032

Beletić A, Dudvarski-Ilić A, Milenković B, Nagorni-Obradović L, Ljujić M, Đorđević V, Mirković D, Radojković D, Majkić-Singh N. Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?. in Biochemia Medica. 2014;24(2):293-298.
doi:10.11613/BM.2014.032 .

Beletić, Anđelo, Dudvarski-Ilić, Aleksandra, Milenković, Branislava, Nagorni-Obradović, Ljudmila, Ljujić, Mila, Đorđević, Valentina, Mirković, Duško, Radojković, Dragica, Majkić-Singh, Nada, "Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?" in Biochemia Medica, 24, no. 2 (2014):293-298,
https://doi.org/10.11613/BM.2014.032 . .

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  - Nagorni-Obradović, Ljudmila
AU  - Ignjatović, Svetlana
AU  - Bosnjak-Petrović, V
AU  - Mitić-Milikić, Marija
PY  - 2005
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/598
AB  - We evaluated magnesium (Mg) in serum and 24-hour urine in patients with acute and chronic pulmonary diseases. Mg was determined in 114 patients, 56 with acute pulmonary diseases (group I) and 58 patients with acute exacerbation of chronic obstructive pulmonary disease (group II), at the start (To) and at the end of hospital treatment (T1). In group I, in period To, there were disturbances of Mg in serum in 14 patients (25%) which decreased in period T1 and persisted in 4 patients (7.1%) (p  lt  0.05). In group II the distribution of normal, decreased and increased Mg in serum was similar in periods To and T1 (p > 0.05). Hypomagnesemia was found in 9 patients (16.1%) in group I at the start of treatment (To), with accompanying increased Mg in 24-hour urine in only 4 patients (7.2%). Extrarenal elimination of Mg or transcellular distribution was a possibility. In group II in period To there was a proportional ratio between hypomagnesemia (12-20.7% patients) and increased concentration of Mg in 24-hour urine (20-34.5% patients) probably due to renal loss. Simultaneous determination and follow-up of Mg in serum and in 24-hour urine can give information about electrolyte disturbances in acute and chronic pulmonary diseases.
PB  - Clin Lab Publ, Heidelberg
T2  - Clinical Laboratory
T1  - Evaluation of magnesium in serum and urine in patients with pulmonary diseases
VL  - 51
IS  - 11-12
SP  - 647
EP  - 652
UR  - https://hdl.handle.net/21.15107/rcub_farfar_598
ER  - 

@article{
author = "Nagorni-Obradović, Ljudmila and Ignjatović, Svetlana and Bosnjak-Petrović, V and Mitić-Milikić, Marija",
year = "2005",
abstract = "We evaluated magnesium (Mg) in serum and 24-hour urine in patients with acute and chronic pulmonary diseases. Mg was determined in 114 patients, 56 with acute pulmonary diseases (group I) and 58 patients with acute exacerbation of chronic obstructive pulmonary disease (group II), at the start (To) and at the end of hospital treatment (T1). In group I, in period To, there were disturbances of Mg in serum in 14 patients (25%) which decreased in period T1 and persisted in 4 patients (7.1%) (p  lt  0.05). In group II the distribution of normal, decreased and increased Mg in serum was similar in periods To and T1 (p > 0.05). Hypomagnesemia was found in 9 patients (16.1%) in group I at the start of treatment (To), with accompanying increased Mg in 24-hour urine in only 4 patients (7.2%). Extrarenal elimination of Mg or transcellular distribution was a possibility. In group II in period To there was a proportional ratio between hypomagnesemia (12-20.7% patients) and increased concentration of Mg in 24-hour urine (20-34.5% patients) probably due to renal loss. Simultaneous determination and follow-up of Mg in serum and in 24-hour urine can give information about electrolyte disturbances in acute and chronic pulmonary diseases.",
publisher = "Clin Lab Publ, Heidelberg",
journal = "Clinical Laboratory",
title = "Evaluation of magnesium in serum and urine in patients with pulmonary diseases",
volume = "51",
number = "11-12",
pages = "647-652",
url = "https://hdl.handle.net/21.15107/rcub_farfar_598"
}

Nagorni-Obradović, L., Ignjatović, S., Bosnjak-Petrović, V.,& Mitić-Milikić, M.. (2005). Evaluation of magnesium in serum and urine in patients with pulmonary diseases. in Clinical Laboratory
Clin Lab Publ, Heidelberg., 51(11-12), 647-652.
https://hdl.handle.net/21.15107/rcub_farfar_598

Nagorni-Obradović L, Ignjatović S, Bosnjak-Petrović V, Mitić-Milikić M. Evaluation of magnesium in serum and urine in patients with pulmonary diseases. in Clinical Laboratory. 2005;51(11-12):647-652.
https://hdl.handle.net/21.15107/rcub_farfar_598 .

Nagorni-Obradović, Ljudmila, Ignjatović, Svetlana, Bosnjak-Petrović, V, Mitić-Milikić, Marija, "Evaluation of magnesium in serum and urine in patients with pulmonary diseases" in Clinical Laboratory, 51, no. 11-12 (2005):647-652,
https://hdl.handle.net/21.15107/rcub_farfar_598 .

TY  - JOUR
AU  - Nagorni-Obradović, Ljudmila
AU  - Ignjatović, Svetlana
AU  - Petrović, Vesna
AU  - Mitić-Milikić, Marija
PY  - 2004
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/564
AB  - In this study we determined magnesium concentration in serum and in 24-hour urine, at the start (To) and at the end of treatment (T1), in 56 patients with acute pulmonary disease (B1) and in 58 patients with chronic obstructive pulmonary disease - COPD (B2). In group B1 there was disbalance of Mg in serum in 14-25% patients at the start of treatment (To) which decreased significantly at the end of treatment (T1) and persisted in 4-7.1% patients (p  lt  0.05). In group B2 distribution of normal, decreased and increased values of Mg in serum was similar in patients in period To and T1 (p > 0.05). In group B1, 9 (16.1%) patients had hypomagnesemia at the start of treatment (To), which was accompanied by increased concentration of Mg in 24-hour urine of only 4 (7.2%) patients. There is a possibility that there was extrarenal elimination of Mg in patients with acute pulmonary disease or there was some kind of transcellular distribution. In group B2 in period To, there was proportional ratio between hypomagnesemia (12-20.7% patients) and increased concentration of Mg in 24-hour urine (20 -34.5% patients). This could be because of renal loss. Simultaneous determination and follow up of magnesium in serum and in 24-hour urine can give us reliable information about homeostasis of this electrolyte in acute and chronic pulmonary diseases.
AB  - U ovom radu određivana je koncentracija magnezijuma u serumu i u 24-urinu, na početku (To) i na kraju hospitalnog lečenja (T1) kod 56 bolesnika sa akutnim plućnim bolestima (B1) i kod 58 sa hroničnim plućnim bolestima (B2). U grupi B1 postojao je disbalans Mg u serumu kod 14-25% bolesnika na početku lečenja (To) koji se značajno smanjio na kraju lečenja (T1) i postojao je kod 4-7,1% bolesnika (p  lt  0,05). U grupi B2 distribucija normalnih, snizenih i povišenih vrednosti Mg u serumu bila je slična u periodu To i T1 (p> 0,05). Hipomagnezemiju u grupi B1 imalo je 9 (16,1%) bolesnika na početku lečenja (To) što je bilo praćeno povećanom koncentracijom Mg u 24-časovnom urinu samo kod 4 (7,2%) bolesnika. Ovo je bilo moguće zbog ekstrarenalnog gubitka elektrolita ili je došlo do transcelularne preraspodele. U grupi B2 u periodu To postojao je proporcionalni odnos hipomagnezemije (12,0-20,7% bolesnika) sa povećanom koncentracijom Mg u 24-časovnom urinu (20,0-34,5% bolesnika). Ovo je bilo moguće zbog renalne eliminacije elektrolita. Istovremeno određivanje i praćenje magnezijuma u serumu i 24-časovnom urinu daje pouzdane informacije o homeostazi ovog elektrolita kod akutnih i hroničnih plućnih bolesti.
PB  - Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd
T2  - Jugoslovenska medicinska biohemija
T1  - Magnesium serum and urine concentration in patients with acute and chronic pulmonary disease
T1  - Koncentracija magnezijuma u serumu i urinu kod bolesnika sa akutnim i hroničnim plućnim bolestima
VL  - 23
IS  - 2
SP  - 155
EP  - 160
DO  - 10.2298/JMH0402155N
ER  - 

@article{
author = "Nagorni-Obradović, Ljudmila and Ignjatović, Svetlana and Petrović, Vesna and Mitić-Milikić, Marija",
year = "2004",
abstract = "In this study we determined magnesium concentration in serum and in 24-hour urine, at the start (To) and at the end of treatment (T1), in 56 patients with acute pulmonary disease (B1) and in 58 patients with chronic obstructive pulmonary disease - COPD (B2). In group B1 there was disbalance of Mg in serum in 14-25% patients at the start of treatment (To) which decreased significantly at the end of treatment (T1) and persisted in 4-7.1% patients (p  lt  0.05). In group B2 distribution of normal, decreased and increased values of Mg in serum was similar in patients in period To and T1 (p > 0.05). In group B1, 9 (16.1%) patients had hypomagnesemia at the start of treatment (To), which was accompanied by increased concentration of Mg in 24-hour urine of only 4 (7.2%) patients. There is a possibility that there was extrarenal elimination of Mg in patients with acute pulmonary disease or there was some kind of transcellular distribution. In group B2 in period To, there was proportional ratio between hypomagnesemia (12-20.7% patients) and increased concentration of Mg in 24-hour urine (20 -34.5% patients). This could be because of renal loss. Simultaneous determination and follow up of magnesium in serum and in 24-hour urine can give us reliable information about homeostasis of this electrolyte in acute and chronic pulmonary diseases., U ovom radu određivana je koncentracija magnezijuma u serumu i u 24-urinu, na početku (To) i na kraju hospitalnog lečenja (T1) kod 56 bolesnika sa akutnim plućnim bolestima (B1) i kod 58 sa hroničnim plućnim bolestima (B2). U grupi B1 postojao je disbalans Mg u serumu kod 14-25% bolesnika na početku lečenja (To) koji se značajno smanjio na kraju lečenja (T1) i postojao je kod 4-7,1% bolesnika (p  lt  0,05). U grupi B2 distribucija normalnih, snizenih i povišenih vrednosti Mg u serumu bila je slična u periodu To i T1 (p> 0,05). Hipomagnezemiju u grupi B1 imalo je 9 (16,1%) bolesnika na početku lečenja (To) što je bilo praćeno povećanom koncentracijom Mg u 24-časovnom urinu samo kod 4 (7,2%) bolesnika. Ovo je bilo moguće zbog ekstrarenalnog gubitka elektrolita ili je došlo do transcelularne preraspodele. U grupi B2 u periodu To postojao je proporcionalni odnos hipomagnezemije (12,0-20,7% bolesnika) sa povećanom koncentracijom Mg u 24-časovnom urinu (20,0-34,5% bolesnika). Ovo je bilo moguće zbog renalne eliminacije elektrolita. Istovremeno određivanje i praćenje magnezijuma u serumu i 24-časovnom urinu daje pouzdane informacije o homeostazi ovog elektrolita kod akutnih i hroničnih plućnih bolesti.",
publisher = "Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd",
journal = "Jugoslovenska medicinska biohemija",
title = "Magnesium serum and urine concentration in patients with acute and chronic pulmonary disease, Koncentracija magnezijuma u serumu i urinu kod bolesnika sa akutnim i hroničnim plućnim bolestima",
volume = "23",
number = "2",
pages = "155-160",
doi = "10.2298/JMH0402155N"
}

Nagorni-Obradović, L., Ignjatović, S., Petrović, V.,& Mitić-Milikić, M.. (2004). Magnesium serum and urine concentration in patients with acute and chronic pulmonary disease. in Jugoslovenska medicinska biohemija
Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd., 23(2), 155-160.
https://doi.org/10.2298/JMH0402155N

Nagorni-Obradović L, Ignjatović S, Petrović V, Mitić-Milikić M. Magnesium serum and urine concentration in patients with acute and chronic pulmonary disease. in Jugoslovenska medicinska biohemija. 2004;23(2):155-160.
doi:10.2298/JMH0402155N .

Nagorni-Obradović, Ljudmila, Ignjatović, Svetlana, Petrović, Vesna, Mitić-Milikić, Marija, "Magnesium serum and urine concentration in patients with acute and chronic pulmonary disease" in Jugoslovenska medicinska biohemija, 23, no. 2 (2004):155-160,
https://doi.org/10.2298/JMH0402155N . .