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  1. Book ; Online ; Thesis: Computational modeling of low-density lipoprotein transport in human coronary arteries

    Olgaç, Ufuk

    implications for atherosclerosis

    2009  

    Author's details by Ufuk Olgaç
    Language English
    Size Online-Ressource (1 Band), Ill
    Publisher ETH
    Publishing place Zürich
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Diss., Eidgenössische Technische Hochschule ETH Zürich, Nr. 18750--Zürich, 1875
    Database Former special subject collection: coastal and deep sea fishing

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  2. Book ; Online ; Thesis: Computational modeling of low-density lipoprotein transport in human coronary arteries

    Olgaç, Ufuk

    implications for atherosclerosis

    2009  

    Author's details by Ufuk Olgaç
    Language English
    Size Online-Ressource (1 Band), Ill
    Publisher ETH
    Publishing place Zürich
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Diss., Eidgenössische Technische Hochschule ETH Zürich, Nr. 18750--Zürich, 1875
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  3. Article: The Bohr Effect Is Not a Likely Promoter of Renal Preglomerular Oxygen Shunting.

    Olgac, Ufuk / Kurtcuoglu, Vartan

    Frontiers in physiology

    2016  Volume 7, Page(s) 482

    Abstract: The aim of this study was to evaluate whether possible preglomerular arterial-to-venous oxygen shunting is affected by the interaction between renal preglomerular carbon dioxide and oxygen transport. We hypothesized that a reverse (venous-to-arterial) ... ...

    Abstract The aim of this study was to evaluate whether possible preglomerular arterial-to-venous oxygen shunting is affected by the interaction between renal preglomerular carbon dioxide and oxygen transport. We hypothesized that a reverse (venous-to-arterial) shunting of carbon dioxide will increase partial pressure of carbon dioxide and decrease pH in the arteries and thereby lead to increased oxygen offloading and consequent oxygen shunting. To test this hypothesis, we employed a segment-wise three-dimensional computational model of coupled renal oxygen and carbon dioxide transport, wherein coupling is achieved by shifting the oxygen-hemoglobin dissociation curve in dependence of local changes in partial pressure of carbon dioxide and pH. The model suggests that primarily due to the high buffering capacity of blood, there is only marginally increased acidity in the preglomerular vasculature compared to systemic arterial blood caused by carbon dioxide shunting. Furthermore, effects of carbon dioxide transport do not promote but rather impair preglomerular oxygen shunting, as the increase in acidity is higher in the veins compared to that in the arteries. We conclude that while substantial arterial-to-venous oxygen shunting might take place in the postglomerular vasculature, the net amount of oxygen shunted at the preglomerular vasculature appears to be marginal.
    Language English
    Publishing date 2016-10-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2016.00482
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Reply to "Letter to the editor: 'The plausibility of arterial-to-venous oxygen shunting in the kidney: it all depends on radial geometry'".

    Olgac, Ufuk / Kurtcuoglu, Vartan

    American journal of physiology. Renal physiology

    2015  Volume 309, Issue 2, Page(s) F181–2

    MeSH term(s) Humans ; Kidney/metabolism ; Oxygen/metabolism ; Oxygen Consumption/physiology ; Renal Circulation/physiology
    Chemical Substances Oxygen (S88TT14065)
    Language English
    Publishing date 2015-07-15
    Publishing country United States
    Document type Comment ; Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00221.2015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Renal oxygenation: preglomerular vasculature is an unlikely contributor to renal oxygen shunting.

    Olgac, Ufuk / Kurtcuoglu, Vartan

    American journal of physiology. Renal physiology

    2015  Volume 308, Issue 7, Page(s) F671–88

    Abstract: The primary aim of this study was to assess the plausibility of preglomerular arterial-to-venous oxygen shunting in the kidney. To this end, we have developed a segment-wise three-dimensional computational model that takes into account transport ... ...

    Abstract The primary aim of this study was to assess the plausibility of preglomerular arterial-to-venous oxygen shunting in the kidney. To this end, we have developed a segment-wise three-dimensional computational model that takes into account transport processes in arteries, veins, cortical tissue, and capillaries. Our model suggests that the amount of preglomerular oxygen shunting is negligible. Consequently, it is improbable that preglomerular shunting contributes to the hypothesized regulation of renal oxygenation. Cortical tissue oxygenation is more likely determined by the interplay between oxygen supply, either from the preglomerular vasculature or from capillaries, and oxygen consumption. We show that reported differences in permeability to oxygen between perfused and unperfused tissue may be explained by what we refer to as advection-facilitated diffusion. We further show that the preglomerular vasculature is the primary source of oxygen for the tissue when cortical consumption is high or renal arterial blood is highly oxygenated, i.e., under hyperoxemic conditions. Conversely, when oxygen demand in the tissue is decreased, or under hypoxemic conditions, oxygen is supplied predominantly by capillaries.
    MeSH term(s) Arteries/physiology ; Computer Simulation ; Humans ; Kidney/blood supply ; Kidney/metabolism ; Oxygen/metabolism ; Oxygen Consumption/physiology ; Renal Circulation/physiology ; Veins/physiology
    Chemical Substances Oxygen (S88TT14065)
    Language English
    Publishing date 2015-04-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00551.2014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book ; Online: Computational modeling of low-density lipoprotein transport in human coronary arteries, implications for atherosclerosis

    Olgaç, Ufuk

    2009  

    Abstract: Diss., Eidgenössische Technische Hochschule ETH Zürich, Nr. 18750, ... ...

    Abstract Diss., Eidgenössische Technische Hochschule ETH Zürich, Nr. 18750, 2009
    Keywords LOW DENSITY LIPOPROTEINE (BLUTPROTEINE) ; PROTEINTRANSPORT + PEPTIDTRANSPORT (MEMBRANBIOLOGIE) ; ENDOTHELZELLEN (CYTOLOGIE ; HISTOLOGIE) ; HERZKRANZGEFÄSSE (ANATOMIE UND PHYSIOLOGIE) ; COMPUTERANWENDUNGEN IN DEN BIOWISSENSCHAFTEN UND DER MEDIZIN ; MODELLRECHNUNG UND SIMULATION IN DER MEDIZIN
    Language English
    Publisher Zürich, ETH
    Publishing country ch
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Quantifying the relative contributions of different solute carriers to aggregate substrate transport.

    Taslimifar, Mehdi / Oparija, Lalita / Verrey, Francois / Kurtcuoglu, Vartan / Olgac, Ufuk / Makrides, Victoria

    Scientific reports

    2017  Volume 7, Page(s) 40628

    Abstract: Determining the contributions of different transporter species to overall cellular transport is fundamental for understanding the physiological regulation of solutes. We calculated the relative activities of Solute Carrier (SLC) transporters using the ... ...

    Abstract Determining the contributions of different transporter species to overall cellular transport is fundamental for understanding the physiological regulation of solutes. We calculated the relative activities of Solute Carrier (SLC) transporters using the Michaelis-Menten equation and global fitting to estimate the normalized maximum transport rate for each transporter (V
    MeSH term(s) Animals ; Biological Transport ; Humans ; Kinetics ; Leucine/metabolism ; Membrane Transport Proteins/metabolism ; Models, Biological ; Oocytes/metabolism ; Phenylalanine/metabolism ; Substrate Specificity ; Xenopus laevis/metabolism
    Chemical Substances Membrane Transport Proteins ; Phenylalanine (47E5O17Y3R) ; Leucine (GMW67QNF9C)
    Language English
    Publishing date 2017-01-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep40628
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  8. Article ; Online: Drug deposition in coronary arteries with overlapping drug-eluting stents.

    Rikhtegar, Farhad / Edelman, Elazer R / Olgac, Ufuk / Poulikakos, Dimos / Kurtcuoglu, Vartan

    Journal of controlled release : official journal of the Controlled Release Society

    2016  Volume 238, Page(s) 1–9

    Abstract: Drug-eluting stents are accepted as mainstream endovascular therapy, yet concerns for their safety may be under-appreciated. While failure from restenosis has dropped to below 5%, the risk of stent thrombosis and associated mortality remain relatively ... ...

    Abstract Drug-eluting stents are accepted as mainstream endovascular therapy, yet concerns for their safety may be under-appreciated. While failure from restenosis has dropped to below 5%, the risk of stent thrombosis and associated mortality remain relatively high. Further optimization of drug release is required to minimize thrombosis risk while maintaining therapeutic dose. The complex three-dimensional geometry of deployed stents together with the combination of diffusive and advective drug transport render an intuitive understanding of the situation exceedingly difficult. In situations such as this, computational modeling has proven essential, helping define the limits of efficacy, determine the mode and mechanism of drug release, and identify alternatives to avoid toxicity. A particularly challenging conformation is encountered in coronary arteries with overlapping stents. To study hemodynamics and drug deposition in such vessels we combined high-resolution, multi-scale ex vivo computed tomography with a flow and mass transfer computational model. This approach ensures high geometric fidelity and precise, simultaneous calculation of blood flow velocity, shear stress and drug distribution. Our calculations show that drug uptake by the arterial tissue is dependent both on the patterns of flow disruption near the wall, as well as on the relative positioning of drug-eluting struts. Overlapping stent struts lead to localized peaks of drug concentration that may increase the risk of thrombosis. Such peaks could be avoided by anisotropic stent structure or asymmetric drug release designed to yield homogeneous drug distribution along the coronary artery and, at the least, suggest that these issues need to remain in the forefront of consideration in clinical practice.
    Language English
    Publishing date 2016-09-28
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2016.07.023
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    Zs.A 2055: Show issues Location:
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  9. Article ; Online: A root cause analysis to identify the mechanistic drivers of immunogenicity against the anti-VEGF biotherapeutic brolucizumab.

    Kearns, Jeffrey D / Wassmann, Paul / Olgac, Ufuk / Fichter, Marie / Christen, Brigitte / Rubic-Schneider, Tina / Koepke, Stephan / Cochin de Billy, Benjamin / Ledieu, David / Andre, Cedric / Hawtin, Stuart / Fischer, Benoit / Moretti, Francesca / Hug, Christian / Bepperling, Alexander / Brannetti, Barbara / Mendez-Garcia, Celia / Littlewood-Evans, Amanda / Clemens, Andreas /
    Grosskreutz, Cynthia L / Mehan, Pawan / Schmouder, Robert L / Sasseville, Vito / Brees, Dominique / Karle, Anette C

    Science translational medicine

    2023  Volume 15, Issue 681, Page(s) eabq5068

    Abstract: Immunogenicity against intravitreally administered brolucizumab has been previously described and associated with cases of severe intraocular inflammation, including retinal vasculitis/retinal vascular occlusion (RV/RO). The presence of antidrug ... ...

    Abstract Immunogenicity against intravitreally administered brolucizumab has been previously described and associated with cases of severe intraocular inflammation, including retinal vasculitis/retinal vascular occlusion (RV/RO). The presence of antidrug antibodies (ADAs) in these patients led to the initial hypothesis that immune complexes could be key mediators. Although the formation of ADAs and immune complexes may be a prerequisite, other factors likely contribute to some patients having RV/RO, whereas the vast majority do not. To identify and characterize the mechanistic drivers underlying the immunogenicity of brolucizumab and the consequence of subsequent ADA-induced immune complex formation, a translational approach was performed to bridge physicochemical characterization, structural modeling, sequence analysis, immunological assays, and a quantitative systems pharmacology model that mimics physiological conditions within the eye. This approach revealed that multiple factors contributed to the increased immunogenic potential of brolucizumab, including a linear epitope shared with bacteria, non-natural surfaces due to the single-chain variable fragment format, and non-native drug species that may form over prolonged time in the eye. Consideration of intraocular drug pharmacology and disease state in a quantitative systems pharmacology model suggested that immune complexes could form at immunologically relevant concentrations modulated by dose intensity. Assays using circulating immune cells from treated patients or treatment-naïve healthy volunteers revealed the capacity of immune complexes to trigger cellular responses such as enhanced antigen presentation, platelet aggregation, endothelial cell activation, and cytokine release. Together, these studies informed a mechanistic understanding of the clinically observed immunogenicity of brolucizumab and associated cases of RV/RO.
    MeSH term(s) Humans ; Antigen-Antibody Complex ; Root Cause Analysis ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Inflammation ; Angiogenesis Inhibitors ; Intravitreal Injections
    Chemical Substances brolucizumab (XSZ53G39H5) ; Antigen-Antibody Complex ; Antibodies, Monoclonal, Humanized ; Angiogenesis Inhibitors
    Language English
    Publishing date 2023-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abq5068
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  10. Article: Computational modeling of coupled blood-wall mass transport of LDL: effects of local wall shear stress.

    Olgac, Ufuk / Kurtcuoglu, Vartan / Poulikakos, Dimos

    American journal of physiology. Heart and circulatory physiology

    2007  Volume 294, Issue 2, Page(s) H909–19

    Abstract: The work herein represents a novel approach for the modeling of low-density lipoprotein (LDL) transport from the artery lumen into the arterial wall, taking into account the effects of local wall shear stress (WSS) on the endothelial cell layer and its ... ...

    Abstract The work herein represents a novel approach for the modeling of low-density lipoprotein (LDL) transport from the artery lumen into the arterial wall, taking into account the effects of local wall shear stress (WSS) on the endothelial cell layer and its pathways of volume and solute flux. We have simulated LDL transport in an axisymmetric representation of a stenosed coronary artery, where the endothelium is represented by a three-pore model that takes into account the contributions of the vesicular pathway, normal junctions, and leaky junctions also employing the local WSS to yield the overall volume and solute flux. The fraction of leaky junctions is calculated as a function of the local WSS based on published experimental data and is used in conjunction with the pore theory to determine the transport properties of this pathway. We have found elevated levels of solute flux at low shear stress regions because of the presence of a larger number of leaky junctions compared with high shear stress regions. Accordingly, we were able to observe high LDL concentrations in the arterial wall in these low shear stress regions despite increased filtration velocity, indicating that the increase in filtration velocity is not sufficient for the convective removal of LDL.
    MeSH term(s) Algorithms ; Atherosclerosis/metabolism ; Atherosclerosis/physiopathology ; Blood Vessels/metabolism ; Computer Simulation ; Constriction, Pathologic/physiopathology ; Coronary Vessels/metabolism ; Coronary Vessels/physiology ; Diffusion ; Electrophysiology ; Endothelium, Vascular/metabolism ; Finite Element Analysis ; Humans ; Intercellular Junctions/metabolism ; Intercellular Junctions/ultrastructure ; Lipoproteins, LDL/blood ; Lipoproteins, LDL/metabolism ; Models, Statistical ; Shear Strength
    Chemical Substances Lipoproteins, LDL
    Language English
    Publishing date 2007-12-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.01082.2007
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