Browsing by Author "Gavrović-Jankulović, Marija (6603098036)"

Modest progress has been made in understanding the role of trace elements as endocrine disruptors. The aim of this study was to examine whether there is a change in the content of trace elements in thyroid disease, as well as whether the ratio of elements could be considered a blood marker for thyroid disease. In addition, this study examined the influence of biological and clinical/pathological parameters on the elemental profile. Blood samples from patients diagnosed with multinodular goiter (MNG), thyroid adenoma (TA), and thyroid cancer (TC) were examined and compared with control samples using chemometric analysis. The concentrations of essential (Mn, Co, Cu, Zn, Se) and toxic elements (Ni, As, Cd, Pb, U) were determined by ICP-MS. This study showed for the first time that the content of Mn, Co, Ni, Cu, Zn, Se, and Pb in pathological blood samples was significantly lower compared to the control, while opposite results were obtained for As, Cd, and U. Based on the classification model, the most important trace metals for discrimination of MNG and TC from the control group (CG) were Co and Zn, while Co, Zn, and Mn influenced the distinction of CG from TA. Moreover, it was found that Cu/Zn and U/Se ratios had significantly increased values in pathological blood samples leading to the possibility of establishing new circulating screening markers. These findings can represent significant translational information since these diseases are widespread and the diagnostic procedure is still difficult in many cases. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Modest progress has been made in understanding the role of trace elements as endocrine disruptors. The aim of this study was to examine whether there is a change in the content of trace elements in thyroid disease, as well as whether the ratio of elements could be considered a blood marker for thyroid disease. In addition, this study examined the influence of biological and clinical/pathological parameters on the elemental profile. Blood samples from patients diagnosed with multinodular goiter (MNG), thyroid adenoma (TA), and thyroid cancer (TC) were examined and compared with control samples using chemometric analysis. The concentrations of essential (Mn, Co, Cu, Zn, Se) and toxic elements (Ni, As, Cd, Pb, U) were determined by ICP-MS. This study showed for the first time that the content of Mn, Co, Ni, Cu, Zn, Se, and Pb in pathological blood samples was significantly lower compared to the control, while opposite results were obtained for As, Cd, and U. Based on the classification model, the most important trace metals for discrimination of MNG and TC from the control group (CG) were Co and Zn, while Co, Zn, and Mn influenced the distinction of CG from TA. Moreover, it was found that Cu/Zn and U/Se ratios had significantly increased values in pathological blood samples leading to the possibility of establishing new circulating screening markers. These findings can represent significant translational information since these diseases are widespread and the diagnostic procedure is still difficult in many cases. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Background: Multiple drug hypersensitivity (MDH) has been defined as a hypersensitivity to two or more chemically different drugs. Two types of MDH have been reported: the first one, which develops to different drugs administered simultaneously and the second type, in which sensitizations develop sequentially. In children, studies which diagnose MDH on the basis of positive allergologic tests to 2 or more chemically different drugs are lacking. Methods: We conducted a prospective study evaluating children with histories of MDH by skin tests, patch tests, serum-specific IgE assays, and drug provocation tests. Results: A MDH was diagnosed in 7 (2.5%) of the 279 children evaluated who completed the study. The responsible drugs were β-lactams (penicillins and cephalosporins) in 5 episodes, ibuprofen and anticonvulsants in 3, and erythromycin, fentanyl, methylprednisolone, and cotrimoxazole in 1. Sensitivity to 2 chemically different drugs was diagnosed in 6 children and to 3 drugs in 1 child. Two of the 7 children presented the first type of MDH, whereas 5 displayed the second one. Conclusions: MDH can occur in children, even to drugs other than antibiotics. It is crucial to evaluate children with histories of MDH using both in vivo and in vitro allergologic tests, including challenges. In fact, such approach allows the physician to confirm the diagnosis of MDH in a small percentage of children with histories of MDH, as well as to rule it out in the great majority of them. © 2012 John Wiley & Sons A/S.

Background: Multiple drug hypersensitivity (MDH) has been defined as a hypersensitivity to two or more chemically different drugs. Two types of MDH have been reported: the first one, which develops to different drugs administered simultaneously and the second type, in which sensitizations develop sequentially. In children, studies which diagnose MDH on the basis of positive allergologic tests to 2 or more chemically different drugs are lacking. Methods: We conducted a prospective study evaluating children with histories of MDH by skin tests, patch tests, serum-specific IgE assays, and drug provocation tests. Results: A MDH was diagnosed in 7 (2.5%) of the 279 children evaluated who completed the study. The responsible drugs were β-lactams (penicillins and cephalosporins) in 5 episodes, ibuprofen and anticonvulsants in 3, and erythromycin, fentanyl, methylprednisolone, and cotrimoxazole in 1. Sensitivity to 2 chemically different drugs was diagnosed in 6 children and to 3 drugs in 1 child. Two of the 7 children presented the first type of MDH, whereas 5 displayed the second one. Conclusions: MDH can occur in children, even to drugs other than antibiotics. It is crucial to evaluate children with histories of MDH using both in vivo and in vitro allergologic tests, including challenges. In fact, such approach allows the physician to confirm the diagnosis of MDH in a small percentage of children with histories of MDH, as well as to rule it out in the great majority of them. © 2012 John Wiley & Sons A/S.

IgE-mediated food allergy affects 6-8% of children. Our study aimed to define the correlations between the results obtained with skin prick tests (SPTs) using commercial extracts and fresh foods, and the correlations between these result and those obtained with specific IgE (sIgE) and/ or challenge. Children aged from 2 months to 6 years were recruited prospectively. Overall 571 children were positive to one food. In all children we performed SPT using commercial extracts of suspected food and fresh foods and sIgE. If SPT and sIgE test results did not correspond to the history, we performed open oral food challenge. Sensitivity of SPT with commercial extracts for all tested food was poor (3-35%), while sensitivity of fresh food skin prick tests (FFSPT) was excellent (50-100%), and showed correlation with open oral food challenge (p<0.001). Our results suggest that fresh food extracts are more effective in detecting sensitization and with levels of sIgE greater than class 3 could predict clinical reactivity, without the need for potentially hazardous food challenges. Copyright © Spring 2017, Iran J Allergy Asthma Immunol. All rights reserved.

Background: Antiepileptic drugs (AEDs) can cause hypersensitivity reactions in children. These reactions are mainly cutaneous, self-limiting, and benign, but life-threatening severe cutaneous adverse reactions can occur. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions, if a drug is taken at the same time. The aims of our study were to confirm or rule out the diagnosis of hypersensitivity reactions to AEDs in children and to detect an infection which mimics these reactions. Methods: A prospective survey was conducted in a group of 100 children with histories of hypersensitivity reactions to AEDs by performing patch tests, delayed-reading intradermal test, and, in case of negative results, challenge test. In all children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. Results: Maculopapular exanthema and delayed-appearing urticaria were the most reported hypersensitivity reactions to AEDs. Sixty-six (66%) of 100 children had confirmed hypersensitivity reactions to AEDs. Fifty-nine children had positive patch test. No children had positive challenge tests. The most common AEDs causing hypersensitivity reactions were carbamazepine (45.4%) and lamotrigine (43.6%). Thirty-two children had positive tests for viruses or M pneumoniae, and nine of them had also a positive allergy work-up. Conclusion: Considering that there are no specific tests to distinguish between a viral infection and hypersensitivity reactions to AEDs in the acute phase, a diagnostic work-up should be performed in all children with suspected hypersensitivity reactions to AEDs, as well as infectious agent study, to remove a false label of hypersensitivity. © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Background: Antiepileptic drugs (AEDs) can cause hypersensitivity reactions in children. These reactions are mainly cutaneous, self-limiting, and benign, but life-threatening severe cutaneous adverse reactions can occur. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions, if a drug is taken at the same time. The aims of our study were to confirm or rule out the diagnosis of hypersensitivity reactions to AEDs in children and to detect an infection which mimics these reactions. Methods: A prospective survey was conducted in a group of 100 children with histories of hypersensitivity reactions to AEDs by performing patch tests, delayed-reading intradermal test, and, in case of negative results, challenge test. In all children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. Results: Maculopapular exanthema and delayed-appearing urticaria were the most reported hypersensitivity reactions to AEDs. Sixty-six (66%) of 100 children had confirmed hypersensitivity reactions to AEDs. Fifty-nine children had positive patch test. No children had positive challenge tests. The most common AEDs causing hypersensitivity reactions were carbamazepine (45.4%) and lamotrigine (43.6%). Thirty-two children had positive tests for viruses or M pneumoniae, and nine of them had also a positive allergy work-up. Conclusion: Considering that there are no specific tests to distinguish between a viral infection and hypersensitivity reactions to AEDs in the acute phase, a diagnostic work-up should be performed in all children with suspected hypersensitivity reactions to AEDs, as well as infectious agent study, to remove a false label of hypersensitivity. © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Novel allergen immunotherapy (AIT) approaches necessitate the use of more effective and safe therapeutics, which can be accomplished by employing novel adjuvants for improved innate immune cell activation, as well as hypoallergenic allergen forms. In this study, we investigate the immunomodulatory effects of a chimera rBet v 1a-BanLecwt (rBv1a-BLwt; Cwt) composed of the major birch pollen allergen Bet v 1a and banana lectin (BanLecwt; BLwt) and two novel chimeras, rBv1l-BLH84T (rBet v 1l-BanLecH84T; C1) and rBLH84T-Bv1l (rBanLecH84T-Bet v 1l; C2), both composed of BLH84T and hypoallergenic birch pollen allergen Bv1l in the co-culture model Caco-2/THP-1, and PBMCs from donors with birch pollen allergy. The chimeric molecules rBv1l-BLH84T (C1) and rBLH84T-Bv1l (C2) were created in silico and then produced in E. coli using recombinant DNA technology. Real-time PCR analysis of gene expression following compound treatment in the co-culture model revealed that all three chimeras have the potential to induce the anti-inflammatory cytokine IL-10 gene expression in Caco-2 cells and IFN-γ gene expression in THP-1 cells. Sandwich ELISA revealed that Cwt increased IL-10 secretion and IFN-/IL-4 levels in PBMCs from birch pollen allergic donors, whereas C1 and C2 were less effective. The findings suggest that Cwt should be analyzed further due to its potential benefit in AIT. © 2024 Elsevier B.V.

Novel allergen immunotherapy (AIT) approaches necessitate the use of more effective and safe therapeutics, which can be accomplished by employing novel adjuvants for improved innate immune cell activation, as well as hypoallergenic allergen forms. In this study, we investigate the immunomodulatory effects of a chimera rBet v 1a-BanLecwt (rBv1a-BLwt; Cwt) composed of the major birch pollen allergen Bet v 1a and banana lectin (BanLecwt; BLwt) and two novel chimeras, rBv1l-BLH84T (rBet v 1l-BanLecH84T; C1) and rBLH84T-Bv1l (rBanLecH84T-Bet v 1l; C2), both composed of BLH84T and hypoallergenic birch pollen allergen Bv1l in the co-culture model Caco-2/THP-1, and PBMCs from donors with birch pollen allergy. The chimeric molecules rBv1l-BLH84T (C1) and rBLH84T-Bv1l (C2) were created in silico and then produced in E. coli using recombinant DNA technology. Real-time PCR analysis of gene expression following compound treatment in the co-culture model revealed that all three chimeras have the potential to induce the anti-inflammatory cytokine IL-10 gene expression in Caco-2 cells and IFN-γ gene expression in THP-1 cells. Sandwich ELISA revealed that Cwt increased IL-10 secretion and IFN-/IL-4 levels in PBMCs from birch pollen allergic donors, whereas C1 and C2 were less effective. The findings suggest that Cwt should be analyzed further due to its potential benefit in AIT. © 2024 Elsevier B.V.

[No abstract available]

[No abstract available]

The purpose of this study was to establish reference values (RVs) for the occupationally- and environmentally-important toxic elements in the whole blood of adult Serbian population for the first time. Contaminated drinking water with arsenic, high share of smokers in the country, removing tetraethyl lead from the gasoline and war attack at the end of the twentieth century were some of the reasons to provide background information for arsenic (As), cadmium (Cd), lead (Pb), thorium (Th), and uranium (U) in the blood of the Serbian population. The whole blood samples were collected from the healthy respondents living in the Belgrade and surrounding areas of the capital (n = 305; w/m ratio = 154/151; mean age: 41 ± 2). The concentrations of toxic metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Reference values were estimated as the lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI), together with the selected percentiles (P2.5-P97.5). The obtained geometric mean (GM) for As, Cd, Pb, Th, and U were: 0.50 ng/g, 0.32 ng/g, 20.94 ng/g, 0.30 ng/g, and 0.06 ng/g, respectively. The influences of age, sex and lifestyle on results were considered. Women have significantly higher levels of Cd and Th than men. The increased level of Th was observed in the aged group below 40 years, while smokers had significantly higher levels of Pb and double higher level of Cd in the blood than non-smokers (p < 0.05). In comparison with other population groups worldwide, the Serbian population had significantly higher levels of Th and U (up to 100 times higher). These findings could contribute to better understanding of the molecular basis for the development of various health hazards, including the increased incidence of cancer among the Serbian population which need be confirmed by clinical studies. © 2018 Elsevier Inc.

The purpose of this study was to establish reference values (RVs) for the occupationally- and environmentally-important toxic elements in the whole blood of adult Serbian population for the first time. Contaminated drinking water with arsenic, high share of smokers in the country, removing tetraethyl lead from the gasoline and war attack at the end of the twentieth century were some of the reasons to provide background information for arsenic (As), cadmium (Cd), lead (Pb), thorium (Th), and uranium (U) in the blood of the Serbian population. The whole blood samples were collected from the healthy respondents living in the Belgrade and surrounding areas of the capital (n = 305; w/m ratio = 154/151; mean age: 41 ± 2). The concentrations of toxic metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Reference values were estimated as the lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI), together with the selected percentiles (P2.5-P97.5). The obtained geometric mean (GM) for As, Cd, Pb, Th, and U were: 0.50 ng/g, 0.32 ng/g, 20.94 ng/g, 0.30 ng/g, and 0.06 ng/g, respectively. The influences of age, sex and lifestyle on results were considered. Women have significantly higher levels of Cd and Th than men. The increased level of Th was observed in the aged group below 40 years, while smokers had significantly higher levels of Pb and double higher level of Cd in the blood than non-smokers (p < 0.05). In comparison with other population groups worldwide, the Serbian population had significantly higher levels of Th and U (up to 100 times higher). These findings could contribute to better understanding of the molecular basis for the development of various health hazards, including the increased incidence of cancer among the Serbian population which need be confirmed by clinical studies. © 2018 Elsevier Inc.