CFD CHARACTERIZATION OF FLOW PATTERN AROUND ENDOTHELIAL CELL IN DENGUE INFECTION WITH PLASMA LEAKAGE

2015 ◽  
Vol 76 (7) ◽  
Author(s):  
Nur Kaliwantoro ◽  
Marsetyawan HNE Soesatyo ◽  
Indarto Indarto ◽  
Mohammad Juffrie ◽  
Rini Dharmastiti ◽  
...  
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Dengue Virus ◽  
Fluid Dynamic ◽  
Dengue Infection ◽  
Leading Edge ◽  
Cell Junction ◽  
Computational Domain ◽  
Permeable Membrane ◽  
Plasma Leakage

Plasma leakage is the pathological hall mark in dengue infection and may cause fatal condition to the patients. In this paper, the CFD (computational fluid dynamic) model is adopted to characterize the flow on the endothelial cells surface with plasma leakage based on in vitro experiments of HUVEC (human umbilical vein endothelial cell) culture on the permeable membrane. The computational domain used is a simplified model of single cell. At the leading edge of the domain and among the membranes, the gaps are modeled as a representation of cell-cell junction breakdown caused by dengue virus infection.  The result shows that at the leading edge , the fluid starts to move more quickly and increases to the maximum value at the middle of the cell and then drops to zero at the trailing edge. From the physical point of view, this result describes that there is a variation of the values of the wall shear stress due to the velocity gradient. These results can be considered as a first step to develop the ways of the prevention of the dengue infection through manipulation the shear stress to reduce the potency of dengue virus to attach the cell surface.  

scholarly journals Serotype Infectivity and Phylogenetic of Dengue Virus cause of Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) in Surabaya- Indonesia

2020 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Fedik Rantam
Keyword(s):  
Phylogenetic Analysis ◽  
Nucleotide Sequence ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Rt Pcr ◽  
Who Criteria ◽  
Plasma Leakage ◽  
Degree Of Severity

Infection with DENV causes a spectrum of clinical disease ranging. The aim of this study is to investigate the infectivity of DENV with degree of severity dengue infection in Surabaya. Dengue infection was established by IgM anti dengue, and two step multiplex RT PCR and Nucleotide sequence. Grading of degree severity infection follow the WHO criteria 2011. DSS cases found 3 from 36 patients caused by DENV 2. The most uninfective was DENV 1, and the most prevalence dengue infection caused  by  DENV  3.  The  infectivity of  dengue  infection shown 16 patients lead to severity with plasma leakage. All of sera patients detecting using multiplex RT-PCR were positive, but it were analyzed using Duo ELISA only 22 serum sera positive IgM and IgG from 36 sera. . The Phylogenetic analysis indicates that the isolates from 2011 to 2012 close related with dengue isolate from 1998 and belong to 2009 to 2020.In this study it indicates that DENV 2 predominantly is the cause of DSS.

Design and Fabrication of a Constant Shear Microfluidic Network for Tissue Engineering

2004 ◽  
Vol 820 ◽  
Author(s):  
E.J. Weinberg ◽  
J.T. Borenstein ◽  
M.R. Kaazempur-Mofrad ◽  
B. Orrick ◽  
J.P. Vacanti
Keyword(s):  
Tissue Engineering ◽  
Blood Flow ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Dynamic Properties ◽  
Fluid Dynamic ◽  
Three Dimensional ◽  
Cell Behavior

AbstractRecent progress in microfabrication of biodegradable materials has resulted in the development of a three-dimensional construct suitable for use as a scaffold for engineering blood vessel networks. These networks are designed to replicate the critical fluid dynamic properties of physiological systems such as the microcirculation within a vital organ. Ultimately, these 3D microvascular constructs will serve as a framework for population with organ-specific cells for applications in organ assist and organ replacement. This approach for tissue engineering utilizes highly engineered designs and microfabrication technology to assemble cells in three-dimensional constructs which have physiological values for properties such as mechanical strength, oxygen, nutrient and waste transport, and fluidic parameters such as flow volume and pressure.Three-dimensional networks with appropriate values for blood flow velocity, pressure drop and hematocrit distribution have been designed and fabricated using replica molding techniques, and populated with endothelial cells for long-term microfluidic cell culture. One critical aspect of the fluid dynamics of these systems is the shear stress exerted by blood flow at the walls of the vessel; a key parameter because of well-known mechanotransduction phenomena from mechanical shear forces which govern endothelial cell behavior. In this work, we report the design and construction of three-dimensional microfluidic constructs for tissue engineering which have uniform wall shear stress throughout the network. This type of control over the shear stress offers several advantages over earlier approaches, including more uniform seeding, more rapid achievement of confluent coatings, and better control over endothelial cell behavior for in vitro and in vivo studies.

scholarly journals The shear stress of it all: the cell membrane and mechanochemical transduction

2007 ◽  
Vol 362 (1484) ◽  
pp. 1459-1467 ◽  
Author(s):  
Charles R White ◽  
John A Frangos
Keyword(s):  
Signal Transduction ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Cell Membrane ◽  
Fluid Shear Stress ◽  
Cell Function ◽  
Vascular Endothelial Cells ◽  
Cell Junction ◽  
Ligand Interaction ◽  
Endothelial Cell Function

As the inner lining of the vessel wall, vascular endothelial cells are poised to act as a signal transduction interface between haemodynamic forces and the underlying vascular smooth-muscle cells. Detailed analyses of fluid mechanics in atherosclerosis-susceptible regions of the vasculature reveal a strong correlation between endothelial cell dysfunction and areas of low mean shear stress and oscillatory flow with flow recirculation. Conversely, steady shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. The molecular basis of shear-induced mechanochemical signal transduction and the endothelium's ability to discriminate between flow profiles remains largely unclear. Given that fluid shear stress does not involve a traditional receptor/ligand interaction, identification of the molecule(s) responsible for sensing fluid flow and mechanical force discrimination has been difficult. This review will provide an overview of the haemodynamic forces experienced by the vascular endothelium and its role in localizing atherosclerotic lesions within specific regions of the vasculature. Also reviewed are several recent lines of evidence suggesting that both changes in membrane microviscosity linked to heterotrimeric G proteins, and the transmission of tension across the cell membrane to the cell–cell junction where known shear-sensitive proteins are localized, may serve as the primary force-sensing elements of the cell.

scholarly journals Increased Production of Interleukin-8 in Primary Human Monocytes and in Human Epithelial and Endothelial Cell Lines after Dengue Virus Challenge

2002 ◽  
Vol 76 (11) ◽  
pp. 5588-5597 ◽  
Author(s):  
Irene Bosch ◽  
Kris Xhaja ◽  
Luis Estevez ◽  
Gregory Raines ◽  
Heather Melichar ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Virus Infection ◽  
Dengue Virus ◽  
Cell Lines ◽  
Hemorrhagic Fever ◽  
Nuclear Factor ◽  
Human Monocytes ◽  
Dengue Virus Infection ◽  
Plasma Leakage

ABSTRACT The more severe form of dengue virus infection, dengue hemorrhagic fever, is characterized by plasma leakage and derangements in hemostasis. As elevated interleukin-8 (IL-8) levels have been observed in sera from patients with more severe disease manifestations, a study was initiated to look at the effect of dengue virus infection in vitro on proinflammatory cytokine secretion and expression. A significant increase in IL-8 levels in the culture supernatant of primary human monocytes infected with dengue 2 virus (D2V) New Guinea C (NGC) was found by enzyme-linked immunosorbent assay. Additionally, by reverse transcriptase PCR, the mRNA was also augmented. Among the proinflammatory cytokines and their mRNAs measured (IL-6, IL-1β, IL-8, and tumor necrosis factor alpha), IL-8 showed the greatest change following D2V infection. Similarly, two cell lines, 293T (a human epithelial cell line) and ECV304 (an endothelial cell line), were permissive to D2V NGC and responded to the infection by increasing the synthesis of IL-8. Nuclear factor kappa B (NF-κB) and nuclear factor IL-6 (NFIL-6) are primary mediators of IL-8 expression. We studied the transcriptional regulation of IL-8 in the ECV304 and 293T cell lines and found that the induction of IL-8 gene expression involved the activation of NF-κB (P = 0.001) and, to a lesser extent, the activation of NFIL-6 in ECV304 cells only. We next observed by the chromatin immunoprecipitation procedure in vivo acetylation of core histones bound to the IL-8 promoter after D2V infection. IL-8 produced by infected monocytes and also IL-8 that may be produced by endothelial or other epithelial cells is associated with the hyperacetylation of histones bound to the IL-8 promoter in addition to the activation of transcription by NF-κB. We hypothesize that the overall increase in IL-8 synthesis observed in this in vitro study may play a role in the pathogenesis of the plasma leakage seen in dengue hemorrhagic fever and dengue shock syndrome.

Design and Fabrication of a Constant Shear Microfluidic Network for Tissue Engineering

2004 ◽  
Vol 823 ◽  
Author(s):  
E.J. Weinberg ◽  
J.T. Borenstein ◽  
M.R. Kaazempur-Mofrad ◽  
B. Orrick ◽  
J.P. Vacanti
Keyword(s):  
Tissue Engineering ◽  
Blood Flow ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Dynamic Properties ◽  
Fluid Dynamic ◽  
Three Dimensional ◽  
Cell Behavior

AbstractRecent progress in microfabrication of biodegradable materials has resulted in the development of a three-dimensional construct suitable for use as a scaffold for engineering blood vessel networks. These networks are designed to replicate the critical fluid dynamic properties of physiological systems such as the microcirculation within a vital organ. Ultimately, these 3D microvascular constructs will serve as a framework for population with organ-specific cells for applications in organ assist and organ replacement. This approach for tissue engineering utilizes highly engineered designs and microfabrication technology to assemble cells in three-dimensional constructs which have physiological values for properties such as mechanical strength, oxygen, nutrient and waste transport, and fluidic parameters such as flow volume and pressure.Three-dimensional networks with appropriate values for blood flow velocity, pressure drop and hematocrit distribution have been designed and fabricated using replica molding techniques, and populated with endothelial cells for long-term microfluidic cell culture. One critical aspect of the fluid dynamics of these systems is the shear stress exerted by blood flow at the walls of the vessel; a key parameter because of well-known mechanotransduction phenomena from mechanical shear forces which govern endothelial cell behavior. In this work, we report the design and construction of three-dimensional microfluidic constructs for tissue engineering which have uniform wall shear stress throughout the network. This type of control over the shear stress offers several advantages over earlier approaches, including more uniform seeding, more rapid achievement of confluent coatings, and better control over endothelial cell behavior for in vitro and in vivo studies.

Naturally Produced Extracellular Matrix Is an Excellent Substrate for Canine Endothelial Cell Proliferation and Resistance to Shear Stress on PTFE Vascular Grafts

1997 ◽  
Vol 78 (05) ◽  
pp. 1392-1398 ◽  
Author(s):  
A Schneider ◽  
M Chandra ◽  
G Lazarovici ◽  
I Vlodavsky ◽  
G Merin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Cell Attachment ◽  
Thrombus Formation ◽  
Endothelial Cell Proliferation ◽  
Ptfe Graft ◽  
Vascular Prostheses ◽  
Endothelial Cell Attachment

SummaryPurpose: Successful development of a vascular prosthesis lined with endothelial cells (EC) may depend on the ability of the attached cells to resist shear forces after implantation. The present study was designed to investigate EC detachment from extracellular matrix (ECM) precoated vascular prostheses, caused by shear stress in vitro and to test the performance of these grafts in vivo. Methods: Bovine aortic endothelial cells were seeded inside untreated polytetrafluoro-ethylene (PTFE) vascular graft (10 X 0.6 cm), PTFE graft precoated with fibronectin (FN), or PTFE precoated with FN and a naturally produced ECM (106 cells/graft). Sixteen hours after seeding the medium was replaced and unattached cells counted. The strength of endothelial cell attachment was evaluated by subjecting the grafts to a physiologic shear stress of 15 dynes/cm2 for 1 h. The detached cells were collected and quantitated. PTFE or EC preseeded ECM coated grafts were implanted in the common carotid arteries of dogs. Results: While little or no differences were found in the extent of endothelial cell attachment to the various grafts (79%, 87% and 94% of the cells attached to PTFE, FN precoated PTFE, or FN+ECM precoated PTFE, respectively), the number of cells retained after a shear stress was significanly increased on ECM coated PTFE (20%, 54% and 85% on PTFE, FN coated PTFE, and FN+ECM coated PTFE, respectively, p <0.01). Implantation experiments in dogs revealed a significant increase in EC coverage and a reduced incidence of thrombus formation on ECM coated grafts that were seeded with autologous saphenous vein endothelial cells prior to implantation. Conclusion: ECM coating significantly increased the strength of endothelial cell attachment to vascular prostheses subjected to shear stress. The presence of adhesive macromolecules and potent endothelial cell growth promoting factors may render the ECM a promising substrate for vascular prostheses.

scholarly journals The Lethal(2)-Essential-for-Life [L(2)EFL] Gene Family Modulates Dengue Virus Infection in Aedes aegypti

2020 ◽  
Vol 21 (20) ◽  
pp. 7520
Author(s):  
Lucky R. Runtuwene ◽  
Shuichi Kawashima ◽  
Victor D. Pijoh ◽  
Josef S. B. Tuda ◽  
Kyoko Hayashida ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Cell Line ◽  
Dengue Infection ◽  
Fruit Fly ◽  
Initiation Factor ◽  
Poly I:C ◽  
Gene Products ◽  
Vector Mosquito

Efforts to determine the mosquito genes that affect dengue virus replication have identified a number of candidates that positively or negatively modify amplification in the invertebrate host. We used deep sequencing to compare the differential transcript abundances in Aedes aegypti 14 days post dengue infection to those of uninfected A. aegypti. The gene lethal(2)-essential-for-life [l(2)efl], which encodes a member of the heat shock 20 protein (HSP20) family, was upregulated following dengue virus type 2 (DENV-2) infection in vivo. The transcripts of this gene did not exhibit differential accumulation in mosquitoes exposed to insecticides or pollutants. The induction and overexpression of l(2)efl gene products using poly(I:C) resulted in decreased DENV-2 replication in the cell line. In contrast, the RNAi-mediated suppression of l(2)efl gene products resulted in enhanced DENV-2 replication, but this enhancement occurred only if multiple l(2)efl genes were suppressed. l(2)efl homologs induce the phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the fruit fly Drosophila melanogaster, and we confirmed this finding in the cell line. However, the mechanism by which l(2)efl phosphorylates eIF2α remains unclear. We conclude that l(2)efl encodes a potential anti-dengue protein in the vector mosquito.

scholarly journals Development of Bacteriophage Virus-Like Particle Vaccines Displaying Conserved Epitopes of Dengue Virus Non-Structural Protein 1

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 726
Author(s):  
Nikole L. Warner ◽  
Kathryn M. Frietze
Keyword(s):  
Dengue Virus ◽  
Population Based ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Denv Serotypes ◽  
Conserved Regions ◽  
Virus Like Particle ◽  
Dependent Cell ◽  
Infected Cells ◽  
Plasma Leakage

Dengue virus (DENV) is a major global health problem, with over half of the world’s population at risk of infection. Despite over 60 years of efforts, no licensed vaccine suitable for population-based immunization against DENV is available. Here, we describe efforts to engineer epitope-based vaccines against DENV non-structural protein 1 (NS1). NS1 is present in DENV-infected cells as well as secreted into the blood of infected individuals. NS1 causes disruption of endothelial cell barriers, resulting in plasma leakage and hemorrhage. Immunizing against NS1 could elicit antibodies that block NS1 function and also target NS1-infected cells for antibody-dependent cell cytotoxicity. We identified highly conserved regions of NS1 from all four DENV serotypes. We generated synthetic peptides to these regions and chemically conjugated them to bacteriophage Qβ virus-like particles (VLPs). Mice were immunized two times with the candidate vaccines and sera were tested for the presence of antibodies that bound to the cognate peptide, recombinant NS1 from all four DENV serotypes, and DENV-2-infected cells. We found that two of the candidate vaccines elicited antibodies that bound to recombinant NS1, and one candidate vaccine elicited antibodies that bound to DENV-infected cells. These results show that an epitope-specific vaccine against conserved regions of NS1 could be a promising approach for DENV vaccines or therapeutics to bind circulating NS1 protein.

scholarly journals Dengue Virus Induces the Expression and Release of Endocan from Endothelial Cells by an NS1–TLR4-Dependent Mechanism

2021 ◽  
Vol 9 (6) ◽  
pp. 1305
Author(s):  
Carlos Alonso Domínguez-Alemán ◽  
Luis Alberto Sánchez-Vargas ◽  
Karina Guadalupe Hernández-Flores ◽  
Andrea Isabel Torres-Zugaide ◽  
Arturo Reyes-Sandoval ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cell Activation ◽  
Dengue Infection ◽  
Elevated Serum ◽  
Fold Increase ◽  
Endothelial Cell Activation ◽  
Stimulation Of

A common hallmark of dengue infections is the dysfunction of the vascular endothelium induced by different biological mechanisms. In this paper, we studied the role of recombinant NS1 proteins representing the four dengue serotypes, and their role in promoting the expression and release of endocan, which is a highly specific biomarker of endothelial cell activation. We evaluated mRNA expression and the levels of endocan protein in vitro following the stimulation of HUVEC and HMEC-1 cell lines with recombinant NS1 proteins. NS1 proteins increase endocan mRNA expression 48 h post-activation in both endothelial cell lines. Endocan mRNA expression levels were higher in HUVEC and HMEC-1 cells stimulated with NS1 proteins than in non-stimulated cells (p < 0.05). A two-fold to three-fold increase in endocan protein release was observed after the stimulation of HUVECs or HMEC-1 cells with NS1 proteins compared with that in non-stimulated cells (p < 0.05). The blockade of Toll-like receptor 4 (TLR-4) signaling on HMEC-1 cells with an antagonistic antibody prevented NS1-dependent endocan production. Dengue-infected patients showed elevated serum endocan levels (≥30 ng/mL) during early dengue infection. High endocan serum levels were associated with laboratory abnormalities, such as lymphopenia and thrombocytopenia, and are associated with the presence of NS1 in the serum.

Flow and Thermal Fields in a Pendant Droplet Moving on Lyophobic Surface

2010 ◽  
Author(s):  
Basant Singh Sikarwar ◽  
K. Muralidhar ◽  
Sameer Khandekar
Keyword(s):  
Heat Transfer ◽  
Contact Angle ◽  
Reynolds Number ◽  
Shear Stress ◽  
Heat Transfer Coefficient ◽  
Wall Shear Stress ◽  
Transfer Coefficient ◽  
Maximum Shear Stress ◽  
Computational Domain ◽  
Wall Shear

Clusters of liquid drops growing and moving on physically or chemically textured lyophobic surfaces are encountered in drop-wise mode of vapor condensation. As opposed to film-wise condensation, drops permit a large heat transfer coefficient and are hence attractive. However, the temporal sustainability of drop formation on a surface is a challenging task, primarily because the sliding drops eventually leach away the lyophobicity promoter layer. Assuming that there is no chemical reaction between the promoter and the condensing liquid, the wall shear stress (viscous resistance) is the prime parameter for controlling physical leaching. The dynamic shape of individual droplets, as they form and roll/slide on such surfaces, determines the effective shear interaction at the wall. Given a shear stress distribution of an individual droplet, the net effect of droplet ensemble can be determined using the time averaged population density during condensation. In this paper, we solve the Navier-Stokes and the energy equation in three-dimensions on an unstructured tetrahedral grid representing the computational domain corresponding to an isolated pendant droplet sliding on a lyophobic substrate. We correlate the droplet Reynolds number (Re = 10–500, based on droplet hydraulic diameter), contact angle and shape of droplet with wall shear stress and heat transfer coefficient. The simulations presented here are for Prandtl Number (Pr) = 5.8. We see that, both Poiseuille number (Po) and Nusselt number (Nu), increase with increasing the droplet Reynolds number. The maximum shear stress as well as heat transfer occurs at the droplet corners. For a given droplet volume, increasing contact angle decreases the transport coefficients.

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