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Horemans, B.; Van Holsbeke, C.; Vos, W.; Darchuk, L.; Novakovic, V.; Fontan, A.C.; de Backer, J.; van Grieken, R.; de Backer, W.; De Wael, K. |
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Title |
Particle deposition in airways of chronic respiratory patients exposed to an urban aerosol |
Type |
A1 Journal article |
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Year |
2012 |
Publication |
Environmental science and technology |
Abbreviated Journal |
Environ Sci Technol |
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Volume |
46 |
Issue |
21 |
Pages |
12162-12169 |
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Keywords |
A1 Journal article; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation); Laboratory Experimental Medicine and Pediatrics (LEMP) |
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Abstract |
Urban atmospheres in modern cities carry characteristic mixtures of particulate pollution which are potentially aggravating for chronic respiratory patients (CRP). Although air quality surveys can be detailed, the obtained information is not always useful to evaluate human health effects. This paper presents a novel approach to estimate particle deposition rates in airways of CRP, based on real air pollution data. By combining computational fluid dynamics with physical-chemical characteristics of particulate pollution, deposition rates are estimated for particles of different toxicological relevance, that is, minerals, iron oxides, sea salts, ammonium salts, and carbonaceous particles. Also, it enables some qualitative evaluation of the spatial, temporal, and patient specific effects on the particle dose upon exposure to the urban atmosphere. Results show how heavy traffic conditions increases the deposition of anthropogenic particles in the trachea and lungs of respiratory patients (here, +0.28 and +1.5 μg·h1, respectively). In addition, local and synoptic meteorological conditions were found to have a strong effect on the overall dose. However, the pathology and age of the patient was found to be more crucial, with highest deposition rates for toxic particles in adults with a mild anomaly, followed by mild asthmatic children and adults with severe respiratory dysfunctions (7, 5, and 3 μg·h1, respectively). |
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Place of Publication |
Easton, Pa |
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Wos |
000310665000082 |
Publication Date |
2012-10-04 |
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Series Issue |
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Edition |
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ISSN |
0013-936X;1520-5851; |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
6.198 |
Times cited |
5 |
Open Access  |
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Notes |
; We are grateful for the financial support of n.v. Vooruitzicht. Furthermore, co-workers at the environmental analysis research group are acknowledged for their help in the fieldwork. ; |
Approved |
Most recent IF: 6.198; 2012 IF: 5.257 |
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Call Number |
UA @ lucian @ c:irua:101411 |
Serial |
2557 |
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Author |
de Backer, J.W.; Vos, W.G.; Burnell, P.; Verhulst, S.L.; Salmon, P.; de Clerck, N.; de Backer, W. |
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Title |
Study of the variability in upper and lower airway morphology in Sprague-Dawley rats using modern micro-CT scan-based segmentation techniques |
Type |
A1 Journal article |
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Year |
2009 |
Publication |
The anatomical record: advances in integrative anatomy and evolutionary biology |
Abbreviated Journal |
Anat Rec |
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Volume |
292 |
Issue |
5 |
Pages |
720-727 |
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Keywords |
A1 Journal article; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP) |
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Abstract |
Animal models are being used extensively in pre-clinical and safety assessment studies to assess the effectiveness and safety of new chemical entities and delivery systems. Although never entirely replacing the need for animal testing, the use of computer simulations could eventually reduce the amount of animals needed for research purposes and refine the data acquired from the animal studies. Computational fluid dynamics is a powerful tool that makes it possible to simulate flow and particle behavior in animal or patient-specific respiratory models, for purposes of inhaled delivery. This tool requires an accurate representation of the respiratory system, respiration and dose delivery attributes. The aim of this study is to develop a representative airway model of the Sprague-Dawley rat using static and dynamic micro-CT scans. The entire respiratory tract was modeled, from the snout and nares down to the central airways at the point where no distinction could be made between intraluminal air and the surrounding tissue. For the selection of the representative model, variables such as upper airway movement, segmentation length, airway volume and size are taken into account. Dynamic scans of the nostril region were used to illustrate the characteristic morphology of this region in anaesthetized animals. It could be concluded from this study that it was possible to construct a highly detailed representative model of a Sprague-Dawley rat based on imaging modalities such as micro-CT scans |
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Place of Publication |
New York, N.Y. |
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Wos |
000265766000010 |
Publication Date |
2009-03-25 |
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Edition |
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ISSN |
1932-8486;1932-8494; |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
1.431 |
Times cited |
16 |
Open Access |
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Notes |
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Approved |
Most recent IF: 1.431; 2009 IF: 1.490 |
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Call Number |
UA @ lucian @ c:irua:76455 |
Serial |
3342 |
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Author |
De Backer, L.A.; Vos, W.; de Backer, J.; Van Holsbeke, C.; Vinchurkar, S.; de Backer, W. |
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Title |
The acute effect of budesonide/formoterol in COPD : a multi-slice computed tomography and lung function study |
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A1 Journal article |
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Year |
2012 |
Publication |
European Respiratory Journal |
Abbreviated Journal |
Eur Respir J |
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Volume |
40 |
Issue |
2 |
Pages |
298-305 |
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Keywords |
A1 Journal article; Biophysics and Biomedical Physics; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP) |
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Abstract |
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of chronic obstructive pulmonary disease (COPD) does not always match with other clinical disease descriptors such as exacerbation frequency and quality of life, indicating that forced expiratory volume in 1 s (FEV1) is not a perfect descriptor of the disease. The aim of this study was to find out whether changes in airway geometry after inhalation of the most commonly used inhalation therapy in severe COPD can more adequately be described with an image-based approach than with spirometry. 10 COPD GOLD stage III patients were assessed in a double-blind crossover study. Airway volumes were analysed using segmentation of multi-slice computed tomography (MSCT) images; airway resistance was determined using computational fluid dynamics (CFD). Distal airway volume significantly increased (p=0.011) in patients 4 h after receiving a budesonide/formoterol combination from 9.6+/-4.67 cm(3) to 10.14+/-4.81 cm(3). Also CFD-determined airway resistance significantly decreased (p=0.047) from 0.051+/-0.021 kPa.s.L-1 to 0.043+/- 0.019 kPa.s.L-1. None of the lung function parameters showed a significant change. Only functional residual capacity (FRC) showed a trend to decline (p=0.056). Only the image-based parameters were able to predict the visit at which the combination product was administered. This study showed that imaging is a sensitive, complementary tool to describe changes in airway structure. |
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Place of Publication |
Copenhagen |
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000307291700006 |
Publication Date |
2011-12-20 |
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ISSN |
0903-1936;1399-3003; |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
10.569 |
Times cited |
37 |
Open Access |
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Notes |
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Approved |
Most recent IF: 10.569; 2012 IF: 6.355 |
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Call Number |
UA @ lucian @ c:irua:101113 |
Serial |
3568 |
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de Backer, J.W.; Vos, W.G.; Vinchurkar, S.C.; Claes, R.; Drollmann, A.; Wulfrank, D.; Parizel, P.M.; Germonpré, P.; de Backer, W. |
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Title |
Validation of computational fluid dynamics in CT-based airway models with SPECT/CT1 |
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A1 Journal article |
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Year |
2010 |
Publication |
Radiology |
Abbreviated Journal |
Radiology |
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Volume |
257 |
Issue |
3 |
Pages |
854-862 |
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Keywords |
A1 Journal article; Condensed Matter Theory (CMT); Vision lab; Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP) |
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Abstract |
Purpose: To compare the results obtained by using numerical flow simulations with the results of combined single photon emission computed tomography (SPECT) and computed tomography (CT) and to demonstrate the importance of correct boundary conditions for the numerical methods to account for the large amount of interpatient variability in airway geometry. Materials and Methods: This study was approved by all relevant institutional review boards. All patients gave their signed informed consent. In this study, six patients with mild asthma (three men; three women; overall mean age, 46 years ± 17 [standard deviation]) underwent CT at functional residual capacity and total lung capacity, as well as SPECT/CT. CT data were used for segmentation and computational fluid dynamics (CFD) simulations. A comparison was made between airflow distribution, as derived with (a) SPECT/CT through tracer concentration analysis, (b) CT through lobar expansion measurement, and (c) CFD through flow computer simulation. Also, the heterogeneity of the ventilation was examined. Results: Good agreement was found between SPECT/CT, CT, and CFD in terms of airflow distribution and hot spot detection. The average difference for the internal airflow distribution was less than 3% for CFD and CT versus SPECT/CT. Heterogeneity in ventilation patterns could be detected with SPECT/CT and CFD. Conclusion: This results of this study show that patient-specific computer simulations with appropriate boundary conditions yield information that is similar to that obtained with functional imaging tools, such as SPECT/CT. |
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Place of Publication |
Easton, Pa |
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Wos |
000284469300031 |
Publication Date |
2010-11-17 |
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ISSN |
0033-8419;1527-1315; |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
7.296 |
Times cited |
100 |
Open Access |
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Notes |
; Supported by Novartis. ; |
Approved |
Most recent IF: 7.296; 2010 IF: 6.069 |
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Call Number |
UA @ lucian @ c:irua:85379 |
Serial |
3831 |
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Author |
De Backer, J. |
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Title |
The versatile nature of cytoglobin, the Swiss army knife among globins, with a preference for oxidative stress |
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Doctoral thesis |
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Year |
2023 |
Publication |
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Abbreviated Journal |
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Pages |
XVIII, 232 p. |
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Doctoral thesis; Pharmacology. Therapy; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Proteinscience, proteomics and epigenetic signaling (PPES) |
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Abstract |
Since its discovery 20 years ago, many studies have been performed to gain insight into the functional role of cytoglobin (Cygb). However, Cygb has been proven to be a promiscuous protein. Yet, there is a consensus that Cygb is a cytoprotective protein involved in redox homeostasis. CYGB is a ubiquitously expressed hexacoordinated globin that is highly expressed in melanocytes and is often found to be downregulated during melanocyte-to-melanoma transition. In Chapter III, we investigated the molecular mechanism through which CYGB could be involved in redox regulation. Here, we showed that CYGB contains two redox-sensitive cysteine residues and that the formation of an intramolecular disulfide bridge resulted in the heme group becoming more accessible to external ligands. This supports the hypothesis that Cys38 and Cys83 serve as sensitive redox sensors. In Chapter IV we showed that CYGB mRNA and protein levels were elevated upon exposure to hypoxia. Interestingly, this upregulation was most likely HIF-2α-dependent. We propose that in melanoma, HIF-2α, rather than HIF-1α, positively regulates CYGB under hypoxic conditions in a cell type specific way. In Chapter V, the cytotoxic effect of indirect NTP treatment in two melanoma cell lines with divergent endogenous CYGB expression levels was investigated. We confirmed that NTP endows cytotoxicity that induces cell death through apoptosis and that this was mediated through the production of ROS. Moreover, we showed that CYGB protects melanoma cells from ROS-induced apoptosis by the scavenging of ROS. Interestingly, CYGB expression influenced the expression of NRF2 and HO-1. We identified the lncRNA MEG3 as a possible mechanism through which NRF2 expression and its downstream target HO-1 can be regulated by CYGB. In chapter VI, increased basal ROS levels and higher degree of lipid peroxidation upon RSL3 treatment contributed to the increased sensitivity of CYGB knockdown G361 cells to ferroptosis. Furthermore, transcriptome analysis demonstrates the enrichment of multiple cancer malignancy pathways upon CYGB knockdown, supporting a tumor-suppressive role for CYGB. Remarkably, CYGB expression regulation was identified as a critical determinant of the ferroptosis–pyroptosis therapy response. This suggests that CYGB is involved in the regulation of multiple modes of programmed cell death. FInally, we sought to delineate the RONS that are responsible for plasma-induced ICD. Our results highlight the importance of the short-lived species. Furthermore, we are first to demonstrate that NTP-created vaccine is safely prepared and offers complete protection. Moreover, we provide conclusive evidence that direct application of NTP induces ICD in melanoma. |
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Most recent IF: NA |
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Call Number |
UA @ admin @ c:irua:193568 |
Serial |
7277 |
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