Hemodynamics in stenotic vessels of small diameter under steady state conditions: Effect of viscoelasticity and migration of red blood cells

Biorheology ◽  
2015 ◽  
Vol 52 (3) ◽  
pp. 183-210 ◽  
Author(s):  
Yannis Dimakopoulos ◽  
George Kelesidis ◽  
Sophia Tsouka ◽  
Georgios C. Georgiou ◽  
John Tsamopoulos
Keyword(s):  
Steady State ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Small Diameter ◽  
And Migration

Steady State Ion and Flux Parameters of Sickling Deer Red Blood Cells

1989 ◽  
Vol 565 (1 Sickle Cell D) ◽  
pp. 428-429 ◽  
Author(s):  
P. K. LAUF ◽  
K. WILKIE ◽  
J. STEFKO ◽  
N. C. ADRAGNA
Keyword(s):  
Steady State ◽  
Red Blood Cells ◽  
Blood Cells

scholarly journals High-Throughput Mirna Analysis Suggests Pro-Inflammatory Profile in Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1077-1077
Author(s):  
Matthew Cannon ◽  
Sarah Glass ◽  
Sidney Smith ◽  
Melanie Heinlein ◽  
Rosa Lapalombella ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Research Funding ◽  
Red Cell ◽  
Cell Disease ◽  
Acute Crisis

Abstract BACKGROUND: Mature circulating red blood cells, though devoid of a nucleus, have been shown to contain an abundance of miRNAs. Further, it has been shown that sickle cell patient-derived RBCs have a dramatic difference in miRNA content than normal RBCs. Given that a range of miRNAs are involved in the regulation of immunity, including the release of inflammatory mediators, we hypothesize that miRNAs enriched in circulating red blood cells function to prolong the inflammatory state in sickle cell disease. Further, we hypothesize that these miRNAs can be used as biomarkers for use in the clinic to predict crisis and differentiate acute versus chronic pain. Exploring this miRNA enrichment in circulating red blood cells in sickle cell patients will provide practical insight for the inflammation state and will inform characteristics of patients who may need greater care in the clinic. METHODS: Twenty steady state patients were recruited and categorized according to their chronic pain status and crisis frequency per year. Whole blood was drawn during routine visits to the OSU Wexner Medical Center Hematology Clinic. Additionally, whole blood was drawn from five patients either in acute pain crisis (recruited prior to crisis) or within a few days of crisis. Samples were subject to double gradient centrifugation and red cells were resuspended in Trizol and cryopreserved. MiRNAs were isolated from red cell Trizol suspensions using a commercial isolation kit (QIAGEN Cat#217004). Isolated miRNAs were then subject to a NanoString Human miR (v3) expression assay. Differential expression analysis was conducted to compare miRNAs with at least 1.5 fold difference (p = 0.05) between steady state and acute crisis. Target prediction and GO ontology analysis was performed for statistically significant miRNAs using DIANA Tools mirPath v3. Follow-up qPCRs were performed using TaqMan Advanced miRNA cDNA Synthesis Kit (Cat#A28007) and TaqMan Advanced miRNA Assays (Cat#A25576) to validate the decreased expression of miRNAs. Additional qPCRs were performed using TaqMan Gene Expression Assays (Cat#4331182) to investigate mRNA regulatory effects of significant miRNAs in the total red cell population. Western blots were also performed to investigate regulatory effects of these miRNAs at the protein level. RESULTS & CONCLUSION: Comparison of RBC miRNA profiles from patients during acute crisis to those in steady state shows several significantly decreased (>1.5 fold) miRNAs in crisis. Among these miRs we have found previously uncharacterized miRNAs, hsa-miR-2116-5p and hsa-miR-302d-3p. DIANA tools miRNA analysis software predicts these miRNAs to be involved in regulation of cell-to-cell adhesion pathways through gene transcripts such as Protocadherin Beta 6 (PCDHB6) and Neural Cell Adhesion Molecule 2 (NCAM2). Interestingly, inspection of miRNA predicted targets that fall under significant GO terms also predicts several individual miRNAs to regulate inflammatory response and nociceptive signaling gene transcripts like A20 (TNFAIP3) and Cathepsin S (CTSS). Validation of these miRNAs was performed via qPCR for 5 out of the 6 significantly decreased miRNAs. Of the 5 miRNAs tested, hsa-miR-2116-5p, hsa-miR-302d-3p, and hsa-miR-1246 were validated as having decreased expression in acute crisis patients compared to steady state. qPCRs were then performed to probe for miRNA based regulation of top predicted target mRNA transcripts. Both CTSS and TNFAIP3 showed increased expression of mRNA transcripts in acute crisis patient red cells as compared to steady state. Next, western blot analysis was performed on red cell protein lysate. Interestingly, this analysis revealed a pattern in activated CTSS expression that was independent of acute crisis. Steady state patients reporting chronic pain showed increased activated CTSS compared to those without chronic pain. Activated CTSS was not found in red cell lysates from three normal, non-SCD donors. Taken together, these results suggest that red blood cells may play a larger role in inflammation and pain responses in sickle cell disease than previously thought. Further these results suggest activated CTSS as a potential biomarker for differentiating chronic pain in patients. Follow-up studies are underway to further stratify and investigate these findings. Disclosures Desai: University of Pittsburgh: Research Funding; Ironwood: Other: Adjudication Committee; NIH: Research Funding; FDA: Research Funding; Selexy/Novartis: Research Funding; Pfizer: Research Funding.

scholarly journals Internal magnesium, 2,3-diphosphoglycerate, and the regulation of the steady-state volume of human red blood cells by the Na/K/2Cl cotransport system.

1992 ◽  
Vol 99 (5) ◽  
pp. 721-746 ◽  
Author(s):  
H Mairbäurl ◽  
J F Hoffman
Keyword(s):  
Steady State ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Indirect Evidence ◽  
Red Cells ◽  
Ionophore A23187 ◽  
Red Cell ◽  
Cotransport System ◽  
2,3 Dpg ◽  
In Cells

This study is concerned with the relationship between the Na/K/Cl cotransport system and the steady-state volume (MCV) of red blood cells. Cotransport rate was determined in unfractionated and density-separated red cells of different MCV from different donors to see whether cotransport differences contribute to the difference in the distribution of MCVs. Cotransport, studied in cells at their original MCVs, was determined as the bumetanide (10 microM)-sensitive 22Na efflux in the presence of ouabain (50 microM) after adjusting cellular Na (Nai) and Ki to achieve near maximal transport rates. This condition was chosen to rule out MCV-related differences in Nai and Ki that might contribute to differences in the net chemical driving force for cotransport. We found that in both unfractionated and density-separated red cells the cotransport rate was inversely correlated with MCV. MCV was correlated directly with red cell 2,3-diphosphoglycerate (DPG), whereas total red cell Mg was only slightly elevated in cells with high MCV. Thus intracellular free Mg (Mgifree) is evidently lower in red cells with high 2,3-DPG (i.e., high MCV) and vice versa. Results from flux measurements at their original MCVs, after altering Mgifree with the ionophore A23187, indicated a high Mgi sensitivity of cotransport: depletion of Mgifree inhibited and an elevation of Mgifree increased the cotransport rate. The apparent K0.5 for Mgifree was approximately 0.4 mM. Maximizing Mgifree at optimum Nai and Ki minimized the differences in cotransport rates among the different donors. It is concluded that the relative cotransport rate is regulated for cells in the steady state at their original cell volume, not by the number of copies of the cotransporter but by differences in Mgifree. The interindividual differences in Mgifree, determined primarily by differences in the 2,3-DPG content, are responsible for the differences in the relative cotransport activity that results in an inverse relationship with in vivo differences in MCV. Indirect evidence indicates that the relative cotransport rate, as indexed by Mgifree, is determined by the phosphorylated level of the cotransport system.

scholarly journals Human and murine splenic neutrophils are potent phagocytes of IgG-opsonized red blood cells

2017 ◽  
Vol 1 (14) ◽  
pp. 875-886 ◽  
Author(s):  
Sanne M. Meinderts ◽  
Per-Arne Oldenborg ◽  
Boukje M. Beuger ◽  
Thomas R. L. Klei ◽  
Johanna Johansson ◽  
...  
Keyword(s):  
Steady State ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Major Effect ◽  
Key Points

Key Points In steady state, where no IgGs against RBCs are present, macrophages are the primary phagocytes of RBCs. In conditions where RBCs are IgG-opsonized, neutrophils can have a major effect on RBC clearance.

scholarly journals A theoretical investigation of the frisbee motion of red blood cells in shear flow

2021 ◽  
Vol 16 ◽  
pp. 23
Author(s):  
Thierry Mignon ◽  
Simon Mendez
Keyword(s):  
Steady State ◽  
Shear Flow ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Numerical Solutions ◽  
Shear Rates ◽  
Steady State Solutions ◽  
Low Shear

The dynamics of a single red blood cell in shear flow is a fluid–structure interaction problem that yields a tremendous richness of behaviors, as a function of the parameters of the problem. A low shear rates, the deformations of the red blood cell remain small and low-order models have been developed, predicting the orientation of the cell and the membrane circulation along time. They reproduce the dynamics observed in experiments and in simulations, but they do not simplify the problem enough to enable simple interpretations of the phenomena. In a process of exploring the red blood cell dynamics at low shear rates, an existing model constituted of 5 nonlinear ordinary differential equations is rewritten using quaternions to parametrize the rotations of the red blood cell. Techniques from algebraic geometry are then used to determine the steady-state solutions of the problems. These solutions are relevant to a particular regime where the red blood cell reaches a constant inclination angle, with its membrane rotating around it, and referred to as frisbee motion. Comparing the numerical solutions of the model to the steady-state solutions allows a better understanding of the transition between the most emblematic motions of red blood cells, flipping and tank-treading.

scholarly journals Estimation of the Life Span of Red Blood Cells in the Growing Animal in Different Nutritional States

1965 ◽  
Vol 49 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Melvin W. Carter ◽  
Gennard Matrone ◽  
Carl Metzler
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Life Span ◽  
Red Blood Cells ◽  
Linear Function ◽  
Blood Cells ◽  
Biological Data ◽  
Total Blood ◽  
First Approximation ◽  
Definition Of

In this study the model of Shemin and Rittenberg for estimating the life span of red blood cells was extended so that non-steady-state conditions, exemplified by growth or changing physiological states, might be considered. The parameters were estimated by use of the modified Gauss-Newton method. The biological data that were used came from growing sheep in different physiological states with regard to copper. The model was extended to include changes in total blood hemin and changes in blood hemin synthesis that may occur with time. In the present study a linear function was taken as a first approximation. The model appeared to be a sufficiently good approximation in the study reported herein. It was found, however, that the parameters associated with changes in hemin should be estimated from ancillary measurements such as blood volume, Hb, body weight, etc., in order to obtain a good fit or definition of the model.

The effects of cell ageing on protein synthesis in rainbow trout (Oncorhynchus mykiss) red blood cells

2000 ◽  
Vol 203 (14) ◽  
pp. 2219-2228
Author(s):  
S.G. Lund ◽  
M.C. Phillips ◽  
C.D. Moyes ◽  
B.L. Tufts
Keyword(s):  
Protein Synthesis ◽  
Steady State ◽  
Rainbow Trout ◽  
Heat Shock ◽  
Oncorhynchus Mykiss ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Mrna Levels ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Cell Age

The effects of cell age on protein synthesis were examined in the nucleated red blood cells of rainbow trout (Oncorhynchus mykiss). Total DNA content was unaffected by cell age, whereas total RNA content in young red blood cells was roughly ten times as high as that in old red blood cells. The mRNA levels for haemoglobin, carbonic anhydrase and the chloride/bicarbonate (Cl(−)/HCO(3)(−)) exchanger were also approximately tenfold higher in young red blood cells. Although young red blood cells synthesized roughly five times more protein under steady-state conditions, total protein concentration was not affected by cell age. Despite large reductions in mRNA levels with red blood cell ageing, the concentrations and/or activities of the respiratory proteins were largely preserved. In contrast, the ability to mount a heat shock response was greatly reduced in older red blood cells. Young red blood cells produced 13 times more heat shock protein 70 mRNA following heat shock and four times more 70 kDa protein after recovery. They also transcribed much more heat shock cognate 71 and heat shock factor mRNA than did older red blood cells under steady-state conditions.

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