261,763 research outputs found
Release of anandamide from blood cells
Background: Endogenous ligands of cannabinoid receptors ( endocannabinoids), in particular anandamide ( arachidonylethanolamide), have been recognized as being of crucial importance in a variety of physiological functions. Plasma concentrations of anandamide have been measured in a number of investigations; however, discrepant data on "normal'' anandamide plasma concentrations were reported. Since this might be caused by pre-analytical variables, we investigated the impact of different sample handling conditions on measured plasma anandamide concentrations. Methods: Blood samples were taken from healthy volunteers in EDTA- or heparin-containing tubes; whole blood samples were kept at +4 degrees C, room temperature, or 37 degrees C, respectively, for up to 120 min before obtaining plasma by centrifugation. Plasma anandamide concentrations were measured by an isotope-dilution liquid chromatography tandem mass spectrometry ( LC-MS/MS) method. Results: A marked time- and temperature-dependent increase in plasma anandamide concentrations ex vivo was observed in both EDTA- and heparin-containing tubes. Mean anandamide concentrations approximately doubled when EDTA samples were kept at 4 degrees C for 60 min before centrifugation {[}immediately centrifuged, 1.3 mg/L ( SD 0.3 mg/L); 2.8 mg/L ( SD 0.5 mg/L) after storage for 60 min; n=12). After storage of heparinized whole-blood samples for 120 min at 37 degrees C, a mean plasma anandamide concentration of 11.9 mg/L ( SD 1.8 mg/L) was found. In cell-free plasma, no increase in anandamide concentrations was found. Conclusion: Anandamide is released from blood cells ex vivo at a very high rate; therefore, strictly standardized pre-analytical protocols have to be applied for plasma anandamide determination
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Blood Flow in silico: From Single Cells to Blood Rheology
This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Mesoscale hydrodynamics simulations of red blood cells under flow have provided much new
insight into their shapes and dynamics in microchannel flow. The presented results range from the behavior
of single cells in confinement and the shape changes in sedimentation, to the clustering and arrangement of
many cells in microchannels and the viscosity of red blood cell suspensions under shear flow. The interaction
of red blood cells with other particles and cells, such as white blood cells, platelets, and drug carriers, shows
an essential role of red blood cells in the margination of other blood components
Viscoelastic transient of confined Red Blood Cells
The unique ability of a red blood cell to flow through extremely small
microcapillaries depends on the viscoelastic properties of its membrane. Here,
we study in vitro the response time upon flow startup exhibited by red blood
cells confined into microchannels. We show that the characteristic transient
time depends on the imposed flow strength, and that such a dependence gives
access to both the effective viscosity and the elastic modulus controlling the
temporal response of red cells. A simple theoretical analysis of our
experimental data, validated by numerical simulations, further allows us to
compute an estimate for the two-dimensional membrane viscosity of red blood
cells, Nsm. By comparing our
results with those from previous studies, we discuss and clarify the origin of
the discrepancies found in the literature regarding the determination of
, and reconcile seemingly conflicting conclusions from
previous works
Characterization of a Putative Hemolysin Expressed by Sneathia amnii, a Preterm Birth-associated Pathogen
The gram-negative bacteria Sneathia amnii is a poorly-characterized commensal of the female urogenital tract frequently associated with adverse clinical outcomes such as bacterial vaginosis (BV), amnionitis, and preterm labor. To investigate its potential role in virulence, we sought to identify and characterize virulence determinants produced by S. amnii in an effort to better understand the pathogenesis of infectious preterm birth. Through sequencing of the Sn35 genome (type strain of S. amnii), we identified two genes with amino acid sequence similarity and structural similarity to the filamentous hemagglutinin (FHA) protein of Bordetella pertussis and its Type Vb transporter. Because S. amnii requires human blood components for growth and lyses human red blood cells, we hypothesized that this two-partner system was involved in hemolysis. To characterize the function of the FHA-like protein, a purified, recombinant peptide was used to induce an antibody response. The polyclonal rabbit serum against the antigenic peptide was incubated with S. amnii to block the FHA-like protein prior to the addition of red blood cells. Pre-treatment with the antiserum inhibited hemolytic activity against human erythrocytes suggesting that the FHA-like protein is somehow involved in hemolysis. Additionally, we found that the hemolytic activity of S. amnii was highly specific against human red blood cells; it did not lyse horse or rabbit red blood cells and only minimally lysed sheep red blood cells. Further research efforts will focus on purifying functional FHA-like protein for further characterization and to determine whether it is sufficient to induce hemolysis.https://scholarscompass.vcu.edu/uresposters/1249/thumbnail.jp
Modelling hematopoiesis mediated by growth factors with applications to periodic hematological diseases
Hematopoiesis is a complex biological process that leads to the production
and regulation of blood cells. It is based upon differentiation of stem cells
under the action of growth factors. A mathematical approach of this process is
proposed to carry out explanation on some blood diseases, characterized by
oscillations in circulating blood cells. A system of three differential
equations with delay, corresponding to the cell cycle duration, is analyzed.
The existence of a Hopf bifurcation for a positive steady-state is obtained
through the study of an exponential polynomial characteristic equation with
delay-dependent coefficients. Numerical simulations show that long period
oscillations can be obtained in this model, corresponding to a destabilization
of the feedback regulation between blood cells and growth factors. This
stresses the localization of periodic hematological diseases in the feedback
loop
Following red blood cells in a pulmonary capillary
The red blood cells or erythrocytes are biconcave shaped cells and consist
mostly in a membrane delimiting a cytosol with a high concentration in
hemoglobin. This membrane is highly deformable and allows the cells to go
through narrow passages like the capillaries which diameters can be much
smaller than red blood cells one. They carry oxygen thanks to hemoglobin, a
complex molecule that have very high affinity for oxygen. The capacity of
erythrocytes to load and unload oxygen is thus a determinant factor in their
efficacy. In this paper, we will focus on the pulmonary capillary where red
blood cells capture oxygen. We propose a camera method in order to numerically
study the behavior of the red blood cell along a whole capillary. Our goal is
to understand how erythrocytes geometrical changes along the capillary can
affect its capacity to capture oxygen. The first part of this document presents
the model chosen for the red blood cells along with the numerical method used
to determine and follow their shapes along the capillary. The membrane of the
red blood cell is complex and has been modelled by an hyper-elastic approach
coming from Mills et al (2004). This camera method is then validated and
confronted with a standard ALE method. Some geometrical properties of the red
blood cells observed in our simulations are then studied and discussed. The
second part of this paper deals with the modeling of oxygen and hemoglobin
chemistry in the geometries obtained in the first part. We have implemented a
full complex hemoglobin behavior with allosteric states inspired from
Czerlinski et al (1999).Comment: 17 page
Swinging of red blood cells under shear flow
We reveal that under moderate shear stress (of the order of 0.1 Pa) red blood
cells present an oscillation of their inclination (swinging) superimposed to
the long-observed steady tanktreading (TT) motion. A model based on a fluid
ellipsoid surrounded by a visco-elastic membrane initially unstrained (shape
memory) predicts all observed features of the motion: an increase of both
swinging amplitude and period (1/2 the TT period) upon decreasing the shear
stress, a shear stress-triggered transition towards a narrow shear stress-range
intermittent regime of successive swinging and tumbling, and a pure tumbling
motion at lower shear stress-values.Comment: 4 pages 5 figures submitted to Physical Review Letter
The buckling instability of aggregating red blood cells
Plasma proteins such as fibrinogen induce the aggregation of red blood cells
(RBC) into rouleaux, which are responsible for the pronounced shear thinning
behavior of blood, control the erythro- cyte sedimentation rate (ESR) a common
hematological test and are involved in many situations of physiological
relevance such as structuration of blood in the microcirculation or clot
formation in pathological situations. Confocal microscopy is used to
characterize the shape of RBCs within rouleaux at equilibrium as a function of
macromolecular concentration, revealing the diversity of contact zone
morphology. Three different configurations that have only been partly predicted
before are identified, namely parachute, male-female and sigmoid shapes, and
quantitatively recovered by numerical simulations. A detailed experimental and
theoretical analysis of clusters of two cells shows that the deformation
increases nonlinearly with the interaction energy. Models indicate a forward
bifurcation in which the contacting membrane undergoes a buckling instability
from a flat to a de- formed contact zone at a critical value of the interaction
energy. These results are not only relevant for the understanding of the
morphology and stability of RBC aggregates, but also for a whole class of
interacting soft deformable objects such as vesicles, capsules or cells in
tissues.Comment: 22 pages, 12 figure
An epidemiologic study of early biologic effects of benzene in Chinese workers.
Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans
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