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  1. Article ; Online: The patterns in urine excretion and transvascular fluid exchange in human subjects during intravenous fluid infusion: A quantitative analysis.

    Curry, FitzRoy E / Michel, C Charles

    Clinical physiology and functional imaging

    2024  

    Abstract: Introduction: Investigations of responses of animals and humans to changes of plasma volume are usually reported as average responses of groups of individuals. This ignores considerable quantitative variation between individuals. We examined the ... ...

    Abstract Introduction: Investigations of responses of animals and humans to changes of plasma volume are usually reported as average responses of groups of individuals. This ignores considerable quantitative variation between individuals. We examined the hypothesis that individual responses follow a common temporal pattern with variations reflecting different parameters describing that pattern.
    Methods: We illustrate this approach using data of Hahn, Lindahl and Drobin (Acta Anaesthesiol Scand.2011, 55:987-94) who measured urine volume and haemoglobin dilution of 10 female subjects during intravenous Ringer infusions for 30 min and subsequent 3.5 h. The published time courses were digitised and analysed to determine if a family of mathematical functions accounted for the variation in individual responses.
    Results: Urine excretion was characterised by a time delay (Td) before urine flow increased and a time course of cumulative urine excretion described by a logarithmic function. This logarithmic relation forms the theoretical basis of a family of linear relations describing urine excretion as a function of Td. Measurement of Td enables estimation of subsequent values of urine excretion and thereby the fraction of infused fluid retained in the body.
    Conclusion: The approach might be useful for physiologists and clinical investigators to compare the response to infusion protocols when both test and control responses can be described by linear relations between cumulative urine volume at specific times and Td. The approach may also be useful for clinicians by complementing strategies to guide fluid therapy by enabling the later responses of an individual to be predicted from their earlier response.
    Language English
    Publishing date 2024-05-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2071203-0
    ISSN 1475-097X ; 1475-0961
    ISSN (online) 1475-097X
    ISSN 1475-0961
    DOI 10.1111/cpf.12887
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The Molecular Structure of the Endothelial Glycocalyx Layer (EGL) and Surface Layers (ESL) Modulation of Transvascular Exchange.

    Curry, Fitz-Roy E

    Advances in experimental medicine and biology

    2018  Volume 1097, Page(s) 29–49

    Abstract: There has been rapid progress over the past decade to extend the concept that a quasiperiodic inner endothelial glycocalyx layer (EGL, <300 nm thick, with key components associated with the endothelial cell membrane) forms the primary molecular filter ... ...

    Abstract There has been rapid progress over the past decade to extend the concept that a quasiperiodic inner endothelial glycocalyx layer (EGL, <300 nm thick, with key components associated with the endothelial cell membrane) forms the primary molecular filter between circulating blood and the body tissues. The EGL is common to both continuous and fenestrated microvessels. The revised Starling Principle describing steady-state fluid exchange across the EGL describes new ways to understand transvascular exchange of water and plasma proteins in microvessels in both normal and disturbed states such as hemorrhage and fluid replacement during surgery. At the same time, direct optical observations describe endothelial surface layers (ESLs) with porous outer layers that extend 1-2 μm beyond the EGL. Preliminary analyses of water and plasma protein transport through barriers formed by a thick ESL in series with the EGL indicate that such two-layer structures can have permeability properties that are not consistent with measured water and plasma exchange in microvessels. Such multilayer models provide a basis for future detailed evaluations of both transports across endothelial surface layers and the methods to image components of both the EGL and the ESL. Furthermore changes in the thickness and distribution of thick ESLs in vessels with diameters larger than 50 μm may not reflect functional changes in the inner glycocalyx layer.
    MeSH term(s) Blood Proteins ; Endothelial Cells ; Endothelium, Vascular ; Glycocalyx/chemistry ; Humans ; Models, Molecular ; Molecular Structure
    Chemical Substances Blood Proteins
    Language English
    Publishing date 2018-10-12
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-319-96445-4_2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Layer upon layer: the functional consequences of disrupting the glycocalyx-endothelial barrier in vivo and in vitro.

    Curry, FitzRoy E

    Cardiovascular research

    2017  Volume 113, Issue 6, Page(s) 559–561

    MeSH term(s) Angiopoietin-2 ; Endothelium, Vascular ; Glycocalyx
    Chemical Substances Angiopoietin-2
    Language English
    Publishing date 2017-04-27
    Publishing country England
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvx044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Layer upon layer: The functional consequences of disrupting the glycocalyx -endothelial barrier in vivo and in vitro.

    Curry, FitzRoy E

    Cardiovascular research

    2017  

    Language English
    Publishing date 2017-04-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvx044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Drug delivery: Redefining tumour vascular barriers.

    Curry, Fitz-Roy E

    Nature nanotechnology

    2016  Volume 11, Issue 6, Page(s) 494–496

    MeSH term(s) Drug Carriers ; Drug Delivery Systems ; Humans ; Neoplasms
    Chemical Substances Drug Carriers
    Language English
    Publishing date 2016-02-15
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2254964-X
    ISSN 1748-3395 ; 1748-3387
    ISSN (online) 1748-3395
    ISSN 1748-3387
    DOI 10.1038/nnano.2016.21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Understanding and extending the Starling principle.

    Michel, C Charles / Woodcock, Thomas E / Curry, Fitz-Roy E

    Acta anaesthesiologica Scandinavica

    2020  Volume 64, Issue 8, Page(s) 1032–1037

    Abstract: The Starling Principle states that fluid movements between blood and tissues are determined by differences in hydrostatic and colloid osmotic (oncotic) pressures between plasma inside microvessels and fluid outside them. The Revised Starling Principle ... ...

    Abstract The Starling Principle states that fluid movements between blood and tissues are determined by differences in hydrostatic and colloid osmotic (oncotic) pressures between plasma inside microvessels and fluid outside them. The Revised Starling Principle recognizes that, because microvessels are permeable to macromolecules, a balance of pressures cannot halt fluid exchange. In most tissues, steady oncotic pressure differences between plasma and interstitial fluid depend on low levels of steady filtration from plasma to tissues for which the Revised Principle provides the theory. Plasma volume is normally maintained by fluid losses from filtration being matched by fluid gains from lymph. Steady state fluid uptake into plasma only occurs in tissues such as intestinal mucosa and renal peri-tubular capillaries where a protein-free secretion of adjacent epithelia contributes significantly to interstitial fluid volume and keeps interstitial oncotic pressure low. Steady filtration rates in different tissues are disturbed locally by reflex changes in capillary pressure and perfusion. The rapid overall decline in capillary pressure after acute blood loss initiates rapid fluid uptake from tissue to plasma, that is, autotransfusion. Fluid uptake is transient, being rapid at first then attenuating but low levels may continue for more than an hour. The Revised Principle highlights the role of oncotic pressure of small volumes of interstitial fluid within a sub-compartment surrounding the microvessels rather than the tissue's mean interstitial fluid oncotic pressure. This maximizes oncotic pressure differences when capillary pressure are high and enhances initial absorption rates when pressures are low, accelerating short-term regulation of plasma volume.
    MeSH term(s) Capillary Permeability/physiology ; Humans ; Microvessels/physiology ; Osmoregulation/physiology ; Osmotic Pressure/physiology ; Plasma Volume/physiology
    Language English
    Publishing date 2020-04-27
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80002-8
    ISSN 1399-6576 ; 0001-5172
    ISSN (online) 1399-6576
    ISSN 0001-5172
    DOI 10.1111/aas.13603
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The endothelial glycocalyx: Barrier functions versus red cell hemodynamics: A model of steady state ultrafiltration through a bi-layer formed by a porous outer layer and more selective membrane-associated inner layer.

    Curry, FitzRoy E / Michel, C Charles

    Biorheology

    2019  Volume 56, Issue 2-3, Page(s) 113–130

    Abstract: Background: Ultrastructural investigations of the endothelial glycocalyx reveal a layer adjacent to the cell surface with a structure consistent with the primary  ultrafilter of vascular walls. Theory predicts this layer can be no greater than 200-300 ... ...

    Abstract Background: Ultrastructural investigations of the endothelial glycocalyx reveal a layer adjacent to the cell surface with a structure consistent with the primary  ultrafilter of vascular walls. Theory predicts this layer can be no greater than 200-300 nm thick, a result  to be reconciled with observations that red cells and large macromolecules are excluded  from a region 1 micrometer or more from the cell membrane.
    Objective: To determine whether this apparent inconsistency might be accounted for by a model of steady state water and protein transport through a glycocalyx bi-layer formed by a porous outer layer in series with a more selective inner layer.
    Methods: Expressions for coupled water and albumin fluxes through the two layers were used to describe steady state ultra-filtration though the bi-layer model.
    Results: Albumin accumulates at the interface between the porous layer and the selective inner layer. The osmotic pressure of accumulated albumin significantly modifies the observed permeability properties of the microvessel wall by an effective unstirred layer effect.
    Conclusions: The model places significant constraints on the outer layer permeability properties . The only outer layer properties that are consistent with measured steady state filtration rates and models of red cell flux through microvessels are an albumin permeability coefficient and hydraulic conductivity more than an order of magnitude larger than the those of the inner layer.
    MeSH term(s) Albumins/metabolism ; Animals ; Capillary Permeability/physiology ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Erythrocytes/metabolism ; Glycocalyx/metabolism ; Hemodynamics/physiology ; Microvessels/metabolism ; Models, Biological ; Osmosis ; Porosity ; Protein Transport/physiology ; Ultrafiltration ; Water/metabolism
    Chemical Substances Albumins ; Water (059QF0KO0R)
    Language English
    Publishing date 2019-02-20
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 82015-5
    ISSN 1878-5034 ; 0006-355X
    ISSN (online) 1878-5034
    ISSN 0006-355X
    DOI 10.3233/BIR-180198
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Microperfusion Technique to Investigate Regulation of Microvessel Permeability in Rat Mesentery.

    Curry, Fitz-Roy E / Clark, Joyce F / Adamson, Roger H

    Journal of visualized experiments : JoVE

    2015  , Issue 103

    Abstract: Experiments to measure the permeability properties of individually perfused microvessels provide a bridge between investigation of molecular and cellular mechanisms regulating vascular permeability in cultured endothelial cell monolayers and the ... ...

    Abstract Experiments to measure the permeability properties of individually perfused microvessels provide a bridge between investigation of molecular and cellular mechanisms regulating vascular permeability in cultured endothelial cell monolayers and the functional exchange properties of whole microvascular beds. A method to cannulate and perfuse venular microvessels of rat mesentery and measure the hydraulic conductivity of the microvessel wall is described. The main equipment needed includes an intravital microscope with a large modified stage that supports micromanipulators to position three different microtools: (1) a beveled glass micropipette to cannulate and perfuse the microvessel; (2) a glass micro-occluder to transiently block perfusion and enable measurement of transvascular water flow movement at a measured hydrostatic pressure, and (3) a blunt glass rod to stabilize the mesenteric tissue at the site of cannulation. The modified Landis micro-occlusion technique uses red cells suspended in the artificial perfusate as markers of transvascular fluid movement, and also enables repeated measurements of these flows as experimental conditions are changed and hydrostatic and colloid osmotic pressure difference across the microvessels are carefully controlled. Measurements of hydraulic conductivity first using a control perfusate, then after re-cannulation of the same microvessel with the test perfusates enable paired comparisons of the microvessel response under these well-controlled conditions. Attempts to extend the method to microvessels in the mesentery of mice with genetic modifications expected to modify vascular permeability were severely limited because of the absence of long straight and unbranched microvessels in the mouse mesentery, but the recent availability of the rats with similar genetic modifications using the CRISPR/Cas9 technology is expected to open new areas of investigation where the methods described herein can be applied.
    MeSH term(s) Animals ; Capillary Permeability/physiology ; Male ; Mesentery/blood supply ; Osmotic Pressure ; Perfusion/methods ; Rats ; Rats, Sprague-Dawley ; Venules/physiology
    Language English
    Publishing date 2015-09-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
    ISSN 1940-087X
    ISSN (online) 1940-087X
    DOI 10.3791/53210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Permeability measurements in an individually perfused capillary: the 'squid axon' of the microcirculation (1974).

    Curry, Fitz-Roy E

    Experimental physiology

    2008  Volume 93, Issue 4, Page(s) 444–446

    MeSH term(s) Animals ; Capillary Permeability ; History, 20th Century ; Humans ; Mesentery/blood supply ; Microcirculation ; Perfusion/methods ; Physiology/history ; United Kingdom
    Language English
    Publishing date 2008-04
    Publishing country England
    Document type Biography ; Classical Article ; Historical Article ; Journal Article ; Portraits ; Research Support, N.I.H., Extramural
    ZDB-ID 1016295-1
    ISSN 1469-445X ; 0958-0670
    ISSN (online) 1469-445X
    ISSN 0958-0670
    DOI 10.1113/expphysiol.2007.040097
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Epac1 Is Crucial for Maintenance of Endothelial Barrier Function through A Mechanism Partly Independent of Rac1.

    García-Ponce, Alexander / Schuster, Katharina / Døskeland, Stein-Ove / Reed, Rolf K / Curry, Fitz-Roy E / Waschke, Jens / Radeva, Mariya Y

    Cells

    2020  Volume 9, Issue 10

    Abstract: Epac1 (exchange protein activated by cAMP) stabilizes the endothelial barrier, but detailed studies are limited by the side effects of pharmacological Epac1 modulators and transient transfections. Here, we compare the key properties of barriers between ... ...

    Abstract Epac1 (exchange protein activated by cAMP) stabilizes the endothelial barrier, but detailed studies are limited by the side effects of pharmacological Epac1 modulators and transient transfections. Here, we compare the key properties of barriers between endothelial cells derived from wild-type (WT) and Epac1-knockout (KO) mice myocardium. We found that KO cell layers, unlike WT layers, had low and cAMP-insensitive trans-endothelial resistance (TER). They also had fragmented VE-cadherin staining despite having augmented cAMP levels and increased protein expression of Rap1, Rac1, RhoA, and VE-cadherin. The simultaneous direct activation of Rac1 and RhoA by CN04 compensated Epac1 loss, since TER was increased. In KO-cells, inhibition of Rac1 activity had no additional effect on TER, suggesting that other mechanisms compensate the inhibition of the Rac1 function to preserve barrier properties. In summary, Epac1 is crucial for baseline and cAMP-mediated barrier stabilization through mechanisms that are at least partially independent of Rac1.
    MeSH term(s) Animals ; Antigens, CD/genetics ; Cadherins/genetics ; Cell Membrane Permeability/drug effects ; Cyclic AMP/genetics ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Gene Expression Regulation/drug effects ; Guanine Nucleotide Exchange Factors/genetics ; Humans ; Mice ; Mice, Knockout ; Myocardium/metabolism ; Myocardium/pathology ; Neuropeptides/agonists ; Neuropeptides/genetics ; Signal Transduction/genetics ; Transcriptional Activation/drug effects ; rac1 GTP-Binding Protein/agonists ; rac1 GTP-Binding Protein/genetics ; rap1 GTP-Binding Proteins/drug effects ; rhoA GTP-Binding Protein/agonists ; rhoA GTP-Binding Protein/genetics
    Chemical Substances Antigens, CD ; Cadherins ; Epac protein, mouse ; Guanine Nucleotide Exchange Factors ; Neuropeptides ; Rac1 protein, mouse ; cadherin 5 ; Cyclic AMP (E0399OZS9N) ; Rap1 protein, mouse (EC 3.6.5.2) ; RhoA protein, mouse (EC 3.6.5.2) ; rac1 GTP-Binding Protein (EC 3.6.5.2) ; rap1 GTP-Binding Proteins (EC 3.6.5.2) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
    Language English
    Publishing date 2020-09-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9102170
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