Shape Of Red Blood Cells Research Articles

Рассеяние лазерного пучка на ансамбле асимметричных эритроцитов

An analytical model of laser beam scattering on an inhomogeneous ensemble of red blood cells is constructed. The model takes into account the difference in red blood cells in size, shape, and orientation in space. The connection of the experimentally measured parameter – the visibility of the diffraction pattern – with the characteristic that has the meaning of a measure of the heterogeneity of the blood sample in terms of the size and shape of red blood cells is established. The monotonicity property of this dependence is shown, which makes it possible to estimate the spread of red blood cells by size and shape based on the measurement of the visibility of the diffraction pattern.

Saudi Child with a Novel Mutation Causing Hereditary Spherocytosis, a Case Report corrected in the text

Spherocytosis is a descriptive terminology of red blood cells, which has a spherical shape rather than the normal biconcave shape of the normal red blood cells. Hereditary spherocytosis (HS) is an inherited blood disorder, which has large heterogenic presentation with both autosomal dominant inheritance and less frequently in an autosomal recessive mode of inheritance. Saudi Arabia is known to have high consanguineous marriage, which makes the population on a higher risk of developing different inherited disorders including HS. We are reporting a novel pathological mutation in a child with HS which caused him to have hemolytic anemia since the age of 2 years. To our best knowledge, this is the first time this new mutation is reported in the medical literatures.

In vitro investigation of the antisickling properties of aqueous fruits extracts of Citrus paradisi, Musa acuminata and Malus domestica

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical complications. Many drugs that are available for treating the disease are insufficiently effective, toxic, or too expensive. Therefore, there is a pressing need for safe, effective, and inexpensive therapeutic agents from indigenous plants used in ethnomedicine. In the current study, the potentials of aqueous extracts of Citrus paradisi, Musa acuminata, Malusdomestica fruit in sickle cell disease management were investigated in vitro using P-hydroxybenzoic acid and normal saline as positive and negative control respectively. The method employed the inhibition of sodium metabisulphite induced sickling of HbSS red blood cells, collected from confirmed sickle cell patients. Results obtained showed that; 50 mg/ml aqueous extract of Musa acuminata showed the lowest sickling inhibition (80.3%) at 60 minutes while 1 mg/ml gave the highest inhibition of 97.3% at 90 minutes. For Citrus paradisi, lowest (83.3%) and highest (98%) sickling inhibitions were obtained with 25 mg/ml and 50 mg/ml fruit extracts at 30 minutes and 60 minutes respectively. Malus domestica had the highest antisickling activities of 99% and 99.33% respectively at 30 and 60 minutes. In all, the sickling inhibition was least with Musa acuminata but highest with Malus domestica. Also, highest inhibitions were observed at 60 minutes (optimum time) and 10 mg/ml (optimum concentration). This study has demonstrated that; Malus domestica, Citrus paradisi and Musa acuminata possess antisickling potentials useful in the management or therapy of sickle cell diseases.

Differential diagnosis of thalassemia and iron deficiency anemia using the CellaVision Advanced Red Blood Cell software

Red blood cells (RBCs) in patients with thalassemia and iron deficiency anemia (IDA) exhibit different patterns of morphological changes. However, manual quantitative analysis of the morphological changes in the RBCs is time-consuming and subjective, limiting its use in differential diagnosis. The aim of this study was to evaluate the CellaVision Advanced RBC software as a prescreening tool for differential diagnosis of thalassemia and IDA. The study cohort consisted of 54 thalassemia and 46 IDA cases in the training group and 36 thalassemia and 31 IDA patients in the validation group. The CellaVision DM96 Advanced RBC software was used to analyze the RBC morphology. Specific patterns of quantitative changes in RBC shapes were found in thalassemia and IDA patients. As a single parameter, target cell was the best morphological cell type to distinguish thalassemia from IDA, with an area under the curve (AUC) of 0.79, followed by hypochromatic cells with an AUC of 0.70. Combination of target and hypochromatic cells expressed as a ratio of the percentage of target cells to percentage of hypochromatic cells (T/H ratio) presented better differential diagnostic ability with an AUC of 0.88. A cutoff value of 1.755 for T/H ratio showed a sensitivity and specificity of 80.43% and 81.48% in the training group and 88.89% and 80.65% in the validation group, respectively. Assessment of the T/H ratio using the CellaVision Advanced RBC software represents a relatively simple and economical screening procedure for diagnostic testing of thalassemia and IDA.

Hereditary Spherocytosis Due to a Novel Variant, P.Q1034X, in the Beta Subunit of the Spectrin Gene

Introduction: Hereditary Spherocytosis (HS) is the most common red cell membrane disorder. 25-30% of cases involve the SPTB gene which encodes for β-Spectrin, a protein that maintains red blood cell shape. Heterozygous variants in SPTB are associated with autosomal dominant HS and elliptocytosis. While genetic testing is not routinely done to confirm HS, it is useful in atypical presentations. Case Description: A 1 week old male presented to the pediatric hematology/oncology clinic for anemia. He was born late preterm and had a history of hyperbilirubinemia requiring phototherapy, failure to thrive, and developmental delay. On examination, he was noted to have hypotonia. There was no known family history of hematologic problems. Based on this constellation of signs and symptoms, he had a comprehensive hematologic and genetic workup. On lab evaluation, his peripheral blood smear showed normocytic normochromic red blood cells with some spherocytes, significant polychromasia, normal WBC and normal platelet morphology. His newborn screen was normal, direct coombs' negative, osmotic fragility test was positive, and protein band 3 reduction was abnormal. His abdominal ultrasound was normal. Whole exome sequencing with variant segregation analysis was significant for heterozygosity of the p.Q1034X variant of the SPTB gene. This variant in the SPTB gene has not been previously reported. Discussion: We found a novel, de novo variant in an infant with HS through whole exome sequencing. This variant is predicted to cause loss of normal protein function either through protein truncation or non-mediated mRNA decay resulting in fragile red blood cells. While neither parent was found to carry this mutation, germline mosaicism should not be excluded. Physicians should be aware that prenatal diagnosis is available to address the risk of recurrence in future pregnancies.

Spherization of red blood cells and platelet margination in COPD patients.

Red blood cells (RBCs) in pathological situations undergo biochemical and conformational changes, leading to alterations in rheology involved in cardiovascular events. The shape of RBCs in volunteers and stable and exacerbated chronic obstructive pulmonary disease (COPD) patients was analyzed. The effects of RBC spherization on platelet transport (displacement in the flow field caused by their interaction with RBCs) were studied in vitro and by numerical simulations. RBC spherization was observed in COPD patients compared with volunteers. In in vitro experiments at a shear rate of 100 s-1 , treatment of RBCs with neuraminidase induced greater sphericity, which mainly affected platelet aggregates without changing aggregate size. At 400 s-1 , neuraminidase treatment changes both the size of the aggregates and the number of platelet aggregates. Numerical simulations indicated that RBC spherization induces an increase of the platelet mean square displacement, which is traditionally linked to the platelet diffusion coefficient. RBCs of COPD patients are more spherical than healthy volunteers. Experimentally, RBC spherization induces increased platelet transport to the wall. Additional studies are needed to understand the link between the effect of RBCs on platelet transport and the increased cardiovascular events observed in COPD patients.

Effect of red blood cell shape changes on haemoglobin interactions and dynamics: a neutron scattering study.

By using a combination of experimental neutron scattering techniques, it is possible to obtain a statistical perspective on red blood cell (RBC) shape in suspensions, and the inter-relationship with protein interactions and dynamics inside the confinement of the cell membrane. In this study, we examined the ultrastructure of RBC and protein–protein interactions of haemoglobin (Hb) in them using ultra-small-angle neutron scattering and small-angle neutron scattering (SANS). In addition, we used the neutron backscattering method to access Hb motion on the ns time scale and Å length scale. Quasi-elastic neutron scattering (QENS) experiments were performed to measure diffusive motion of Hb in RBCs and in an RBC lysate. By using QENS, we probed both internal Hb dynamics and global protein diffusion, on the accessible time scale and length scale by QENS. Shape changes of RBCs and variation of intracellular Hb concentration were induced by addition of the Na+-selective ionophore monensin and the K+-selective one, valinomycin. The experimental SANS and QENS results are discussed within the framework of crowded protein solutions, where free motion of Hb is obstructed by mutual interactions.

Математичне моделювання зміни форми еритроцитів в умовах ранньої нейропротекції за помірної терапевтичної дії гіпотермії

Математичне моделювання зміни форми еритроцитів в умовах ранньої нейропротекції за помірної терапевтичної дії гіпотермії

Direct Quantification of Single Red Blood Cell Hemoglobin Concentration with Multiphoton Microscopy.

Blood disorders, diseases, and infections often affect the shape, number, and content of red blood cells (RBCs) dramatically. To combat these pathologies, many therapies target RBCs and their contents directly. Mean corpuscular hemoglobin concentration (MCHC) is an important pathological metric in both identification and treatment. However, current methods for RBC analysis and MCHC quantification rely on bulk measurements. Single RBC measurements could provide necessary insight into the heterogeneity of RBC health and improve therapeutic efficacy. In this study, we present a novel multimodal multiphoton approach for quantifying hemoglobin concentration at single RBC resolution. We achieve this by collecting two images simultaneously that allows us to excite water with stimulated Raman scattering and hemoglobin with transient absorption. This multimodal imaging is enabled by a newly designed orthogonal modulation theme for dual-channel lock-in detection. By leveraging water as an internal standard, we quantify MCHC of healthy RBCs and RBCs infected with Plasmodium yoelii, a commonly studied rodent parasite model.

Dynamics of shape recovery by stored red blood cells during washing at the single cell level.

Hypothermic storage transforms red blood cells (RBC) from smooth biconcave discocytes into increasingly spherical spiculated echinocytes and, ultimately, fragile spherocytes (S). Individual cells undergo this transformation at different rates, producing a heterogeneous mixture of RBCs at all stages of echinocytosis in each unit of stored blood. Here we investigated how washing (known to positively affect RBC properties) changes morphology of individual RBCs at the single-cell level. We tracked the change in shape of individual RBCs (n = 2870; drawn from six 4- to 6-week-old RBC units) that were confined in an array of microfluidic wells during washing in saline (n = 1095), 1% human serum albumin (1% HSA) solution (n = 999), and the autologous storage supernatant (control, n = 776). Shape recovery proceeded through the disappearance of spicules followed by the progressive smoothening of the RBC contour, with the majority of changes occurring within the initial 10 minutes of being exposed to the washing solution. Approximately 57% of all echinocytes recovered by at least one morphologic class when washed in 1% HSA (36% for normal saline), with 3% of cells in late-stage echinocytosis restoring their discoid shape completely. Approximately one-third of all spherocytic cells were lysed in either washing solution. Cells washed in their autologous storage supernatant continued to deteriorate during washing. Our findings suggest that the replacement of storage supernatant with a washing solution during washing induces actual shape recovery for RBCs in all stages of echinocytosis, except for S that undergo lysis instead.

What determines blood viscosity at the highest city in the world?

What determines blood viscosity at the highest city in the world?

The dielectric spectroscopy of human red blood cells during 37-day storage: β-dispersion parameterization

This study exploits dielectric spectroscopy to monitor the kinetics of red blood cells (RBC) storage lesions, focusing on those processes linked to cellular membrane interface known as β-dispersion. The dielectric response of RBC suspensions, exposed to blood-bank cold storage for 37 days, was studied using time-domain dielectric spectroscopy in the frequency range 500 kHz to 200 MHz. The measured dielectric processes are characterized by their dielectric strength (Δε) and their relaxation times (τ). Changes in the dielectric properties of the RBC suspensions, due to storage-related biophysical changes, were evaluated. For a quantitative characterization of RBC vitality, we characterized the shape of fresh and stored RBC and measured their deformability as expressed by their average elongation ratio, which was achieved under a shear stress of 3.0 Pa. During the second week of storage, an increment in the evolution of the relaxation times and in the dielectric permittivity strength of about 25% was observed. We propose that the characteristic increment of ATP, during the second and third weeks of storage, is responsible for the raise of the specific capacitance of cell membrane, which in turn explains the changes observed in the dielectric response when combined with the influence of the shape changes.

Surface Modification of Luminescent LnIII Fluoride Core-Shell Nanoparticles with Acetylsalicylic acid (Aspirin): Synthesis, Spectroscopic and in Vitro Hemocompatibility Studies.

Luminescent lanthanide fluoride core-shell (LaF3 :Tb3+ ,Ce3+ @SiO2 -NH2 ) nanoparticles, with acetylsalicylic acid (aspirin) coated on the surface have been obtained. The synthesized products, which combine the potential located in the silica shell with the luminescent activity of the core, were characterized in detail with the use of luminescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and transmission electron microscopy (TEM) methods. The in vitro effects of the modified luminescent nanoparticles on human red blood cell (RBC) membrane permeability, RBC shape, and sedimentation rate were investigated to assess the hemocompatibility of the obtained compounds. This study demonstrates that LaF3 : Tb3+ 5 %, Ce3+ 10 %@SiO2 -NH2 nanoparticles with acetylsalicylic acid (aspirin) coated on the surface are very good precursors for multifunctional drug-delivery systems or bio-imaging probes that can be used safely in potential biomedical applications.

Active Forces of Myosin Motors May Control Endovesiculation of Red Blood Cells

By using Monte Carlo (MC) simulations, we have shown that the active forces generated by (NMIIA) motor domains bound to F-actin may partially control the endovesiculation of the red blood cell (RBC) membrane. The myosin generated active forces favor pancake-like (torocyte) RBC endovesicles with a large flat central membrane region and a bulby periphery. We suggest that the myosin generated active forces acting on the RBC membrane in the direction perpendicular to the membrane surface towards the interior of the RBC may influence also other RBC shape transformations and the stability of different types of RBC shapes and should be therefore considered in the future theoretical studies of the RBC vesiculation and shape transformations.

Theoretical Bases for the Role of Red Blood Cell Shape in the Regulation of Its Volume.

The red blood cell (RBC) membrane contains a mechanosensitive cation channel Piezo1 that is involved in RBC volume homeostasis. In a recent model of the mechanism of its action it was proposed that Piezo1 cation permeability responds to changes of the RBC shape. The aim here is to review in a descriptive manner different previous studies of RBC behavior that formed the basis for this proposal. These studies include the interpretation of RBC and vesicle shapes based on the minimization of membrane bending energy, the analyses of various consequences of compositional and structural features of RBC membrane, in particular of its membrane skeleton and its integral membrane proteins, and the modeling of the establishment of RBC volume. The proposed model of Piezo1 action is critically evaluated, and a perspective presented for solving some remaining experimental and theoretical problems. Part of the discussion is devoted to the usefulness of theoretical modeling in studies of the behavior of cell systems in general.

Numerical study of forced convection over phase change material capsules in a traditional spherical shape and a biomimetic shape

Abstract The use of biomimetic red blood cell (RBC) shaped capsules for latent heat thermal storage is a novel concept. The RBC shape provides a much higher heat transfer rate than that of other shapes. However, the heat transfer characteristics of external flows around RBC-shaped capsules and the optimal attack angle are unknown. In the present work, forced convection of external flows over an RBC-shaped PCM capsule was numerically studied in a steady-state laminar flow region with Reynolds number in the range of 20–200, and compared to that of a conventional spherical capsule. Moreover, the local Nusselt number, surface-average Nusselt number and drag coefficient at various Reynolds numbers and attack angles of RBC-shaped capsules were investigated. The surface-average Nusselt number of the RBC-shaped capsule was found slightly smaller than that of the spherical capsule with a maximum disparity of 12.04%. The drag coefficient of the RBC and spherical capsule both decreased with the increase of Reynolds number, and the disparity between them was very small. 0° attack angle was recommended for the RBC-shaped capsule layout, as it had the lowest drag force with a relatively high average Nusselt number.

A deep learning AlexNet model for classification of red blood cells in sickle cell anemia

Sickle cell anemia (SCA) is a serious hematological disorder, where affected patients are frequently hospitalized throughout a lifetime and even can cause death. The manual method of detecting and classifying abnormal cells of SCA patient blood film through a microscope is time-consuming, tedious, prone to error, and require a trained hematologist. The affected patient has many cell shapes that show important biomechanical characteristics. Hence, having an effective way of classifying the abnormalities present in the SCA disease will give a better insight into managing the concerned patient's life. This work proposed algorithm in two-phase firstly, automation of red blood cells (RBCs) extraction to identify the RBC region of interest (ROI) from the patient’s blood smear image. Secondly, deep learning AlexNet model is employed to classify and predict the abnormalities presence in SCA patients. The study was performed with (over 9,000 single RBC images) taken from 130 SCA patient each class having 750 cells. To develop a shape factor quantification and general multiscale shape analysis. We reveal that the proposed framework can classify 15 types of RBC shapes including normal in an automated manner with a deep AlexNet transfer learning model. The cell's name classification prediction accuracy, sensitivity, specificity, and precision of 95.92%, 77%, 98.82%, and 90% were achieved, respectively.

Non-uniform distribution of myosin-mediated forces governs red blood cell membrane curvature through tension modulation.

The biconcave disk shape of the mammalian red blood cell (RBC) is unique to the RBC and is vital for its circulatory function. Due to the absence of a transcellular cytoskeleton, RBC shape is determined by the membrane skeleton, a network of actin filaments cross-linked by spectrin and attached to membrane proteins. While the physical properties of a uniformly distributed actin network interacting with the lipid bilayer membrane have been assumed to control RBC shape, recent experiments reveal that RBC biconcave shape also depends on the contractile activity of nonmuscle myosin IIA (NMIIA) motor proteins. Here, we use the classical Helfrich-Canham model for the RBC membrane to test the role of heterogeneous force distributions along the membrane and mimic the contractile activity of sparsely distributed NMIIA filaments. By incorporating this additional contribution to the Helfrich-Canham energy, we find that the RBC biconcave shape depends on the ratio of forces per unit volume in the dimple and rim regions of the RBC. Experimental measurements of NMIIA densities at the dimple and rim validate our prediction that (a) membrane forces must be non-uniform along the RBC membrane and (b) the force density must be larger in the dimple than the rim to produce the observed membrane curvatures. Furthermore, we predict that RBC membrane tension and the orientation of the applied forces play important roles in regulating this force-shape landscape. Our findings of heterogeneous force distributions on the plasma membrane for RBC shape maintenance may also have implications for shape maintenance in different cell types.

Poikilocytosis under dogs’ spontaneous babesiosis

The article presents the results of studies of changes in the shape of red blood cells during spontaneous babesiosis in dogs. It was found that in 2019, seasonal outbreaks are caused and characterized by the presence of two waves – spring-summer with a peak in June and autumn with a peak in October. The intensity of parasitemia increases synchronously with the extensity of infestation in the first half of the year(a narrow direct correlation), in the future it falls and does not correlate with outbreaks of animal disease. Clinically, the spring-summer wave of the disease is characterized by an acute-subacute typical course with pronounced classic clinical signs. The autumn wave had a predominantly subacute-atypical course, with the development of severe complications with signs of hepatopathy and acute renal insufficiency, cardiomyopathy and myocarditis, lesions of the nervous system, the development of shock with a significant tendency to decompensation. Changes in the shape of red blood cells are bright and indicative markers of the state of animals on babesiosis. Poikilocytosis was detected in 92.3 % of sick dogs. The most common changes are acanthocytosis and vacuolization of erythrocytes (irreversible forms), which qualitatively assess the degree of damage to vital organs. Echinocytes are reversible forms that appear in the early stages and determine the development of renal and hepatic pathologies. Stomatocytes accompany the development of inflammatory and dystrophic pathologies, qualitatively characterize the degree of hemolytic anemia. Their intensity is synchronous with the extent of the invasion. The appearance of schizocytes is a formidable symptom that is pathognomonic for disseminated intravascular coagulation syndrome. This marker requires immediate use of intensive care. The assessment of qualitative changes in the form of red blood cells, the calculation of the intensity of erythrocyte lesions allows you to determine the severity of the condition of the body of sick dogs, the degree of metabolic disorders, hemolytic anemia, hepatopathy, the severity of intoxication, uremic syndrome, spleen hyperplasia, as well as identify the development of DIC syndrome, kidney failure and “shock kidney”. Such an assessment is necessary for making timely and adequate decisions regarding therapeutic measures for spontaneous babesiosis of dogs.

Single-cell O2 exchange imaging shows that cytoplasmic diffusion is a dominant barrier to efficient gas transport in red blood cells

Disorders of oxygen transport are commonly attributed to inadequate carrying capacity (anemia) but may also relate to inefficient gas exchange by red blood cells (RBCs), a process that is poorly characterized yet assumed to be rapid. Without direct measurements of gas exchange at the single-cell level, the barriers to O2 transport and their relationship with hematological disorders remain ill defined. We developed a method to track the flow of O2 in individual RBCs by combining ultrarapid solution switching (to manipulate gas tension) with single-cell O2 saturation fluorescence microscopy. O2 unloading from RBCs was considerably slower than previously estimated in acellular hemoglobin solutions, indicating the presence of diffusional barriers in intact cells. Rate-limiting diffusion across cytoplasm was demonstrated by osmotically induced changes to hemoglobin concentration (i.e., diffusive tortuosity) and cell size (i.e., diffusion pathlength) and by comparing wild-type cells with hemoglobin H (HbH) thalassemia (shorter pathlength and reduced tortuosity) and hereditary spherocytosis (HS; expanded pathlength). Analysis of the distribution of O2 unloading rates in HS RBCs identified a subpopulation of spherocytes with greatly impaired gas exchange. Tortuosity imposed by hemoglobin was verified by demonstrating restricted diffusivity of CO2, an acidic gas, from the dissipative spread of photolytically uncaged H+ ions across cytoplasm. Our findings indicate that cytoplasmic diffusion, determined by pathlength and tortuosity, is a major barrier to efficient gas handling by RBCs. Consequently, changes in RBC shape and hemoglobin concentration, which are common manifestations of hematological disorders, can have hitherto unrecognized and clinically significant implications on gas exchange.