TY  - DATA
AU  - Spasovski, Vesna
AU  - Srzentić Dražilov, Sanja
AU  - Nikčević, Gordana
AU  - Baščarević, Zoran
AU  - Stojiljković, Maja
AU  - Pavlović, Sonja
AU  - Spasovski, Duško
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2089
AB  - Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.
PB  - MDPI
T2  - Diagnostics
T1  - Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471.
IS  - 3
SP  - 471
VL  - 13
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2089
ER  - 

@misc{
author = "Spasovski, Vesna and Srzentić Dražilov, Sanja and Nikčević, Gordana and Baščarević, Zoran and Stojiljković, Maja and Pavlović, Sonja and Spasovski, Duško",
year = "2023",
abstract = "Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.",
publisher = "MDPI",
journal = "Diagnostics",
title = "Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471.",
number = "3",
pages = "471",
volume = "13",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2089"
}

Spasovski, V., Srzentić Dražilov, S., Nikčević, G., Baščarević, Z., Stojiljković, M., Pavlović, S.,& Spasovski, D.. (2023). Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471.. in Diagnostics
MDPI., 13(3), 471.
https://hdl.handle.net/21.15107/rcub_imagine_2089

Spasovski V, Srzentić Dražilov S, Nikčević G, Baščarević Z, Stojiljković M, Pavlović S, Spasovski D. Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471.. in Diagnostics. 2023;13(3):471.
https://hdl.handle.net/21.15107/rcub_imagine_2089 .

Spasovski, Vesna, Srzentić Dražilov, Sanja, Nikčević, Gordana, Baščarević, Zoran, Stojiljković, Maja, Pavlović, Sonja, Spasovski, Duško, "Supplementary material for: Spasovski, V.; Srzentić Dražilov, S.; Nikčević, G.; Baščarević, Z.; Stojiljković, M.; Pavlović, S.; Spasovski, D. Molecular Biomarkers in Perthes Disease: A Review. Diagnostics 2023, 13 (3), 471. https://doi.org/10.3390/diagnostics13030471." in Diagnostics, 13, no. 3 (2023):471,
https://hdl.handle.net/21.15107/rcub_imagine_2089 .

TY  - JOUR
AU  - Spasovski, Vesna
AU  - Srzentić Dražilov, Sanja
AU  - Nikčević, Gordana
AU  - Baščarević, Zoran
AU  - Stojiljković, Maja
AU  - Pavlović, Sonja
AU  - Spasovski, Duško
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2088
AB  - Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.
PB  - MDPI
T2  - Diagnostics
T1  - Molecular Biomarkers in Perthes Disease: A Review
IS  - 3
SP  - 471
VL  - 13
DO  - 10.3390/diagnostics13030471
ER  - 

@article{
author = "Spasovski, Vesna and Srzentić Dražilov, Sanja and Nikčević, Gordana and Baščarević, Zoran and Stojiljković, Maja and Pavlović, Sonja and Spasovski, Duško",
year = "2023",
abstract = "Background: Perthes disease is a juvenile form of osteonecrosis of the femoral head that affects children under the age of 15. One hundred years after its discovery, some light has been shed on its etiology and the biological factors relevant to its etiology and disease severity. Methods: The aim of this study was to summarize the literature findings on the biological factors relevant to the pathogenesis of Perthes disease, their diagnostic and clinical significance, and their therapeutic potential. A special focus on candidate genes as susceptibility factors and factors relevant to clinical severity was made, where studies reporting clinical or preclinical results were considered as the inclusion criteria. PubMed databases were searched by two independent researchers. Sixty-eight articles were included in this review. Results on the factors relevant to vascular involvement and inflammatory molecules indicated as factors that contribute to impaired bone remodeling have been summarized. Moreover, several candidate genes relevant to an active phase of the disease have been suggested as possible biological therapeutic targets. Conclusions: Delineation of molecular biomarkers that underlie the pathophysiological process of Perthes disease can allow for the provision of earlier and more accurate diagnoses of the disease and more precise follow-ups and treatment in the early phases of the disease.",
publisher = "MDPI",
journal = "Diagnostics",
title = "Molecular Biomarkers in Perthes Disease: A Review",
number = "3",
pages = "471",
volume = "13",
doi = "10.3390/diagnostics13030471"
}

Spasovski, V., Srzentić Dražilov, S., Nikčević, G., Baščarević, Z., Stojiljković, M., Pavlović, S.,& Spasovski, D.. (2023). Molecular Biomarkers in Perthes Disease: A Review. in Diagnostics
MDPI., 13(3), 471.
https://doi.org/10.3390/diagnostics13030471

Spasovski V, Srzentić Dražilov S, Nikčević G, Baščarević Z, Stojiljković M, Pavlović S, Spasovski D. Molecular Biomarkers in Perthes Disease: A Review. in Diagnostics. 2023;13(3):471.
doi:10.3390/diagnostics13030471 .

Spasovski, Vesna, Srzentić Dražilov, Sanja, Nikčević, Gordana, Baščarević, Zoran, Stojiljković, Maja, Pavlović, Sonja, Spasovski, Duško, "Molecular Biomarkers in Perthes Disease: A Review" in Diagnostics, 13, no. 3 (2023):471,
https://doi.org/10.3390/diagnostics13030471 . .

TY  - JOUR
AU  - Srzentić Dražilov, Sanja
AU  - Spasovski, Vesna
AU  - Spasovski, Duško
AU  - Živković, Zorica
AU  - Matanović, Dragana
AU  - Baščarević, Zoran
AU  - Šupić-Terzić, Zorica
AU  - Stojiljković, Maja
AU  - Karan-Đurašević, Teodora
AU  - Stanković, Biljana
AU  - Pavlović, Sonja
AU  - Nikčević, Gordana
AU  - Vukašinović, Zoran
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/752
AB  - Uvod Pertesova bolest je idiopatska avaskularna osteonekroza proksimalne epifize femura koja se javlja kod dece. Etiologija ove bolesti je nepoznata. Tokom razvoja Pertesove bolesti zastupljen je proces zapaljenja, za koji je pokazano da utiče na remodelovanje koštanog tkiva. Cilj rada S obzirom na to da genetički faktori koji utiču na proces zapaljenja dosad nisu ispitivani kod Pertesove bolesti, cilj ovog istraživanja je bio da se utvrdi povezanost učestalosti varijanti u genima koji učestvuju u inflamatornom odgovoru, TLR4 (engl. toll-like receptor 4) i IL-6 (interleukin 6), i ove bolesti. Metode rada Ispitano je 37 dece s Pertesovom bolešću i 50 zdravih osoba. Metodom PCR-RFLP određeni su polimorfizmi medijatora zapaljenja TLR4 (Asp299Gly, Thr399Ile) i IL-6 (G-174C, G-597A). Rezultati Pokazano je da su polimorfizmi IL-6 G-174C i G-597A u našem ispitivanju bili u potpunoj gametskoj neravnoteži vezanosti. U kontrolnoj grupi je bilo statistički značajno više nosilaca heterozigotnog genotipa IL-6 G-174C/G-597A u poređenju sa grupom ispitanika s Pertesovom bolešću (p=0,047; OR=2,49; 95% CI=1,00-6,21). Takođe, grupa bolesnika nije bila u Hardi- Vajnbergovoj ravnoteži za polimorfizme IL-6 G-174C/G-597A. Nije primećena statistički značajna razlika u raspodeli genotipova za polimorfizme analizirane u TLR4 genu. Raspodela genotipova među grupama bolesnika formiranih na osnovu uzrasta kada se bolest pojavila nije pokazala statistički značajnu povezanost s analiziranim polimorfizmima. Zaključak Naše istraživanje je pokazalo da su nosioci heterozigotnog genotipa za IL-6 G-174C/G-597A polimorfizme bili značajno češći u kontrolnoj grupi nego u grupi dece obolele od Pertesove bolesti. Na osnovu toga zaključili smo da je kod dece koja su nosioci heterozigotnog genotipa za ove polimorfizme manja verovatnoća za razvoj Pertesove bolesti nego kod nosilaca oba homozigotna genotipa.
AB  - Introduction Perthes disease is idiopathic avascular osteonecrosis of the hip in children, with unknown etiology. Inflammation is present during development of Perthes disease and it is known that this process influences bone remodeling. Objective Since genetic studies related to inflammation have not been performed in Perthes disease so far, the aim of this study was to analyze the association of frequencies of genetic variants of immune response genes, toll-like receptor 4 (TLR4) and interleukin-6 (IL-6), with this disease. Methods The study cohort consisted of 37 patients with Perthes disease and 50 healthy controls. Polymorphisms of well described inflammatory mediators: TLR4 (Asp299Gly, Thr399Ile) and IL-6 (G-174C, G- 597A) were determined by polymerase chain reaction restriction fragment length polymorphism method. Results IL-6 G-174C and G-597A polymorphisms were in complete linkage disequilibrium. A statistically significant increase of heterozygote subjects for IL-6 G-174C/G-597A was found in controls in comparison to Perthes patient group (p=0.047, OR=2.49, 95% CI=1.00-6.21). Also, the patient group for IL-6 G-174C/G- 597A polymorphisms was not in Hardy-Weinberg equilibrium. No statistically significant differences were found between patient and control groups for TLR4 analyzed polymorphisms. A stratified analysis by the age at disease onset also did not reveal any significant difference for all analyzed polymorphisms. Conclusion Our study revealed that heterozygote subjects for the IL-6 G-174C/G-597A polymorphisms were significantly overrepresented in the control group than in the Perthes patient group. Consequently, we concluded that children who are heterozygous for these polymorphisms have a lower chance of developing Perthes disease than carriers of both homozygote genotypes.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću
T1  - Association of gene variants in TLR4 and IL-6 genes with Perthes disease
EP  - 456
IS  - 7-8
SP  - 450
VL  - 142
DO  - 10.2298/SARH1408450S
ER  - 

@article{
author = "Srzentić Dražilov, Sanja and Spasovski, Vesna and Spasovski, Duško and Živković, Zorica and Matanović, Dragana and Baščarević, Zoran and Šupić-Terzić, Zorica and Stojiljković, Maja and Karan-Đurašević, Teodora and Stanković, Biljana and Pavlović, Sonja and Nikčević, Gordana and Vukašinović, Zoran",
year = "2014",
abstract = "Uvod Pertesova bolest je idiopatska avaskularna osteonekroza proksimalne epifize femura koja se javlja kod dece. Etiologija ove bolesti je nepoznata. Tokom razvoja Pertesove bolesti zastupljen je proces zapaljenja, za koji je pokazano da utiče na remodelovanje koštanog tkiva. Cilj rada S obzirom na to da genetički faktori koji utiču na proces zapaljenja dosad nisu ispitivani kod Pertesove bolesti, cilj ovog istraživanja je bio da se utvrdi povezanost učestalosti varijanti u genima koji učestvuju u inflamatornom odgovoru, TLR4 (engl. toll-like receptor 4) i IL-6 (interleukin 6), i ove bolesti. Metode rada Ispitano je 37 dece s Pertesovom bolešću i 50 zdravih osoba. Metodom PCR-RFLP određeni su polimorfizmi medijatora zapaljenja TLR4 (Asp299Gly, Thr399Ile) i IL-6 (G-174C, G-597A). Rezultati Pokazano je da su polimorfizmi IL-6 G-174C i G-597A u našem ispitivanju bili u potpunoj gametskoj neravnoteži vezanosti. U kontrolnoj grupi je bilo statistički značajno više nosilaca heterozigotnog genotipa IL-6 G-174C/G-597A u poređenju sa grupom ispitanika s Pertesovom bolešću (p=0,047; OR=2,49; 95% CI=1,00-6,21). Takođe, grupa bolesnika nije bila u Hardi- Vajnbergovoj ravnoteži za polimorfizme IL-6 G-174C/G-597A. Nije primećena statistički značajna razlika u raspodeli genotipova za polimorfizme analizirane u TLR4 genu. Raspodela genotipova među grupama bolesnika formiranih na osnovu uzrasta kada se bolest pojavila nije pokazala statistički značajnu povezanost s analiziranim polimorfizmima. Zaključak Naše istraživanje je pokazalo da su nosioci heterozigotnog genotipa za IL-6 G-174C/G-597A polimorfizme bili značajno češći u kontrolnoj grupi nego u grupi dece obolele od Pertesove bolesti. Na osnovu toga zaključili smo da je kod dece koja su nosioci heterozigotnog genotipa za ove polimorfizme manja verovatnoća za razvoj Pertesove bolesti nego kod nosilaca oba homozigotna genotipa., Introduction Perthes disease is idiopathic avascular osteonecrosis of the hip in children, with unknown etiology. Inflammation is present during development of Perthes disease and it is known that this process influences bone remodeling. Objective Since genetic studies related to inflammation have not been performed in Perthes disease so far, the aim of this study was to analyze the association of frequencies of genetic variants of immune response genes, toll-like receptor 4 (TLR4) and interleukin-6 (IL-6), with this disease. Methods The study cohort consisted of 37 patients with Perthes disease and 50 healthy controls. Polymorphisms of well described inflammatory mediators: TLR4 (Asp299Gly, Thr399Ile) and IL-6 (G-174C, G- 597A) were determined by polymerase chain reaction restriction fragment length polymorphism method. Results IL-6 G-174C and G-597A polymorphisms were in complete linkage disequilibrium. A statistically significant increase of heterozygote subjects for IL-6 G-174C/G-597A was found in controls in comparison to Perthes patient group (p=0.047, OR=2.49, 95% CI=1.00-6.21). Also, the patient group for IL-6 G-174C/G- 597A polymorphisms was not in Hardy-Weinberg equilibrium. No statistically significant differences were found between patient and control groups for TLR4 analyzed polymorphisms. A stratified analysis by the age at disease onset also did not reveal any significant difference for all analyzed polymorphisms. Conclusion Our study revealed that heterozygote subjects for the IL-6 G-174C/G-597A polymorphisms were significantly overrepresented in the control group than in the Perthes patient group. Consequently, we concluded that children who are heterozygous for these polymorphisms have a lower chance of developing Perthes disease than carriers of both homozygote genotypes.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću, Association of gene variants in TLR4 and IL-6 genes with Perthes disease",
pages = "456-450",
number = "7-8",
volume = "142",
doi = "10.2298/SARH1408450S"
}

Srzentić Dražilov, S., Spasovski, V., Spasovski, D., Živković, Z., Matanović, D., Baščarević, Z., Šupić-Terzić, Z., Stojiljković, M., Karan-Đurašević, T., Stanković, B., Pavlović, S., Nikčević, G.,& Vukašinović, Z.. (2014). Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 142(7-8), 450-456.
https://doi.org/10.2298/SARH1408450S

Srzentić Dražilov S, Spasovski V, Spasovski D, Živković Z, Matanović D, Baščarević Z, Šupić-Terzić Z, Stojiljković M, Karan-Đurašević T, Stanković B, Pavlović S, Nikčević G, Vukašinović Z. Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću. in Srpski arhiv za celokupno lekarstvo. 2014;142(7-8):450-456.
doi:10.2298/SARH1408450S .

Srzentić Dražilov, Sanja, Spasovski, Vesna, Spasovski, Duško, Živković, Zorica, Matanović, Dragana, Baščarević, Zoran, Šupić-Terzić, Zorica, Stojiljković, Maja, Karan-Đurašević, Teodora, Stanković, Biljana, Pavlović, Sonja, Nikčević, Gordana, Vukašinović, Zoran, "Povezanost varijanti u genima TLR4 i IL-6 s Pertesovom bolešću" in Srpski arhiv za celokupno lekarstvo, 142, no. 7-8 (2014):450-456,
https://doi.org/10.2298/SARH1408450S . .