Effect of sodium nitroprusside on the microrheological properties of red blood cells in different media

Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.

Using Optical Tweezers to Study the Friction of the Red Blood Cells

In the last two decades the study of red blood cell elasticity using optical tweezers has known a rise appearing in the scientific research with regard to the various works carried out. Despite the various work done, no study has been done so far to study the influence of friction on the red blood cell indentation response using optical tweezers. In this study, we have developed a new approach to determine the coefficient of friction as well as the frictional forces of the red blood cell. This approach therefore allowed us to simultaneously carry out the indentation and traction test, which allowed us to extract the interfacial properties of the microbead red blood cell couple, among other things, the friction coefficient. This property would be extremely important to investigate the survival and mechanical features of cells, which will be of great physiological and pathological significance. But taking into account the hypothesis of friction as defined by the isotropic Coulomb law. The experiment performed for this purpose is the Brinell Hardness Test (DB).

The Popularization and Application of Cold Storage Red Blood Cells or Whole Blood at -80 ℃ of the Rh(D) Negative Patients in Surgical Operation

Summary: The efficiency of cold storage red blood cells (CSRBC) or whole blood at -80 ℃ used in 27 Rh(D) negative patients during surgical operation was reported. The Rh(D) negative patients received the transfusion of CSRBC or whole blood stored at -80 ℃ for 180 to 360 days. The changes in the indexes, such as blood TB, DB, K +, Na +, BUN, Cr, urine protein (URPO), UOB, Hb, HCT, serum total protein, relative to hemolytic reaction and blood volume before and after transfusion were observed. The results showed that after transfusion of CSRBC or whole blood 27 cases were negative for urine protein and UOB, and the levels of BUN and Cr were normal (P>0.05). Blood TB, DB, Hb, and HCT were increased, while pH, blood K + and blood Na + was normal with the difference being not significant before and after operation (P>0.05). Plasma protein was decreased, but there was no significant difference before and after operation (P>0.05). It was suggested that CSRBC or whole blood at -80 ℃ could be safely infused to the Rh(D) negative patients without side effects during the surgical operation.

Cyclic arginine-glycine-aspartic acid-modified red blood cells for drug delivery:Synthesis and in vitro evaluation

Red blood cells(RBCs)are an excellent choice for cell preparation research because of their biocompatibility,high drug loading,and long half-life.In this study,doxorubicin(DOX)was encapsulated with RBCs as the carrier.The biotin-avidin system binding principle was used to modify biotinylated cyclic arginine-glycine-aspartic acid(cRGD)onto RBC surfaces for accurate targeting,high drug loading,and sustained drug release.The RBC drug delivery system(DDS)was characterized,and the concentration of surface sulfur in the energy spectrum was 6.330%.The physical and chemical properties of RBC DDS were as follows:drug content,0.857 mg/mL;particle size,3339 nm;potential value,12.5 mV;and cumulative release rate,81.35%.There was no significant change in RBC morphology for up to seven days.The results of the targeting and cytotoxicity studies of RBC DDS showed that many RBCs covered the surfaces of U251 cells,and the fluorescence intensity was higher than that of MCF-7 cells.The IC50 value of unmodified drug-loaded RBCs was 2.5 times higher than that of targeted modified drug-loaded RBCs,indicating that the targeting of cancer cells produced satisfactory inhibition.This study confirms that the RBC DDS has the characteristics of accurate targeting,high drug loading,and slow drug release,which increases its likelihood of becoming a clinical cancer treatment in the future.

Water Efflux in Red Blood Cells of Sickle Cell Patients under Spontaneous Deoxygenation

The water transport through Red Blood Cells (RBC) membrane has been previously studied in Sickle Cell Disease (SCD) using oxygenated RBC or under complete deoxygenation. In this work, the water efflux in RBC of sickle cell patients was studied under spontaneous deoxygenation conditions. With that purpose, a magnetic resonance method was used to evaluate the water exchange time (τe) and the permeability through the erythrocyte membrane (P) measuring the spin-spin relaxation time (T2) in doped and non-doped RBC. Carr-Purcell-Meiboon-Gill (CPMG) pulse sequence was used to measure T2 in a magnetic resonance console coupled to one homogeneous magnet system (0.095 T). An increase of the water transport in RBC from sickle cell patients was observed and characterized with a τe value of 15.2 ± 0.8 ms. The abnormal activation of the Psickle, Gardos, and potassium chloride cotransporter channels starting from deoxygenation, as well as, the possible appearance of new pores due to the increase of the hemoglobin-membrane interaction, are suggested to explain this abnormal transport phenotype. The change of the water volume to surface ratio (V/S) in the sickle cells is also suggested to be considered in P calculation under deoxygenation. The results obtained in this work increase the fundamental knowledge about molecular mechanism involved in SCD and could be useful in the development of new methods for diagnostic and treatment evaluation.

Improving Oxygen Binding of Desiccated Human Red Blood Cells

Desiccating human red blood cells (RBCs) to increase their storage life has been the subject of intense research for a number of years. However, drying RBCs invariably compromises their integrity and has detrimental effects on hemoglobin function due to autoxidation. We have previously demonstrated an RBC desiccation and rehydration process that preserves RBC antigenic epitopes better than frozen RBCs. This study expands on those observations by examining what effects this desiccation process has on RBC hemoglobin function with respect to oxygen binding properties. In this paper, we examined RBCs from normal donors which were desiccated to 25% moisture content and stored dry for 2 weeks at room temperature prior to rehydration with plasma followed by structural and functional studies. Our data showed that approximately 98% of the RBCs were intact upon rehydration based on hemolysis assays. Oxygen dissociation curves for the desiccated/rehydrated RBCs showed a left shift compared to fresh RBCs (pO2 = 17 mmHg vs. 26 mmHg, respectively). The desiccated/rehydrated RBCs also showed an increase in methemoglobin compared to fresh RBCs (4.5% vs 0.9%, respectively). 2,3-Diphosphoglycerate concentration of the desiccated/rehydrated RBCs was reduced by 20%. In conclusion, although this RBC dehydration process preserves RBC integrity and hemoglobin oxygen binding properties better than most other dehydration techniques described so far, further optimization and long-term studies are needed to make this procedure acceptable for human transfusion.

Static Laser Light Scattering Studies from Red Blood Cells

A homemade Static Light scattering studies has been used to determine angle resolved scattered intensity for different polarization states of the incident laser light. Classical light scattering set ups are being used to study morphological aspects of scatterers using simple set ups using low power lasers. Red blood cells form rather interesting as well as a challenging system for scattering experiments. The scattering spectrometer consists of a scattering arm, a scattering turn table and collimating arm. Along with polarizers integrated in the collimating arm as well as scattering arms ensures collection of scattered flux with the required polarization state. This technique is being developed for its in vitro studies using fresh red blood cells. A brief review of the theoretical models used for scattering from Red Blood Cells (RBC) has been discussed in the paper. Scattering pattern (scattering plots) as well as polar plots of scattered flux have been determined for different polarization state of the incident light. Insight into the orientation of major axis of particles can be inferred from the polar plots.

Enrichment of Fetal Nucleated Red Blood Cells by Multi-core Magnetic Composite Particles for Non-invasive Prenatal Diagnosis

A novel kind of multi-core magnetic composite particles, the surfaces of which were respectively mo- dified with goat-anti-mouse IgG and antitransferrin receptor（anti-CD71）, was prepared. The fetal nucleated red blood cells（FNRBCs） in the peripheral blood of a gravida were rapidly and effectively enriched and separated by the mo- dified multi-core magnetic composite particles in an external magnetic field. The obtained FNRBCs were used for the identification of the fetal sex by means of fluorescence in situ hybridization（FISH） technique. The results demonstrate that the multi-core magnetic composite particles meet the requirements for the enrichment and speration of FNRBCs with a low concentration and the accuracy of detetion for the diagnosis of fetal sex reached to 95%. Moreover, the obtained FNRBCs were applied to the non-invasive diagnosis of Down syndrome and chromosome 3p21 was de- tected. The above facts indicate that the novel multi-core magnetic composite particles-based method is simple, relia- ble and cost-effective and has opened up vast vistas for the potential application in clinic non-invasive prenatal diag- nosis.

Isolation of Fetal Nucleated Red Blood Cells from Maternal Blood

To find a simple, effective method of isolating fetal cells from maternal peripheral blood for prenatal diagnosis, 45 women were studied with their gestation being 6-14 weeks and age 21- 30 years. The fetal cells were isolated from maternal blood by using discontinuous density gradient centrifugation. Some of the isolated cells were made smear and counted under the microscope; others were used for predicting fetal sex by PCR amplification of Y chromosome specific DYZ1 gene. The major cells in the upper separation interface were lymphocytes and monocytes, with occasionally seen nucleated red blood cells (NRBC); while those in the middle separation interface were neutrocytes, with NRBC scattering. The ratio of NRBC/nucleated cells was 1. 98±0. 28× 10-5. There was no significant difference between the first and second trimester (P>0. 05). The amount of isolated fetal cells was sufficient for prenatal genetic diagnosis. Male pregnancy was correctly predicted in 10 out of 13 cases. It is concluded that the method of discontinuous density gradient centrifugation was of considerable importance in the development of non-invasive prenatal genetic diagnosis.

Modeling biomembranes and red blood cells by coarse-grained particle methods

In this work, the previously developed coarse-grained （CG） particle models for biomembranes and red blood cells （RBCs） are reviewed, and the advantages of the CG particle methods over the continuum and atomistic simulations for modeling biological phenomena are discussed. CG particle models can largely increase the length scale and time scale of atomistic simulations by eliminating the fast degrees of freedom while preserving the mesoscopic structures and properties of the simulated system. Moreover, CG particle models can be used to capture the microstructural alternations in diseased RBCs and simulate the topological changes of biomembranes and RBCs, which are the major challenges to the typical continuum representations of membranes and RBCs. The power and versatility of CG particle methods are demonstrated：through simulating the dynamical processes mvolving significant topological .changes e.g. lipid self-assembly vesicle fusion and membrane budding.

Doxorubicin-loaded silicon nanoparticles impregnated into red blood cells featuring bright fluorescence, strong photostability, and lengthened blood residency

Based on the unique advantages of fluorescent silicon nanoparticles （SiNPs）, long circulation red blood cells （RBCs）, and anti-cancer drug molecules （i.e., doxorubicin （DOX））, we developed multifunctional DOX-loaded SiNPs impregnated into RBCs. Importantly, the resulting drug delivery systems （DDSs） simultaneously exhibited bright fluorescence coupled with robust photostability （i.e., - 24% loss of fluorescent intensity after 25 min continuous laser irradiation） and significantly lengthened blood residency （i.e., t1/2 = 7.31 ± 0.96 h, 3.9-fold longer than pure DOX-loaded SiNPs）. Therefore, this novel DDS featuring multi-functionalities shows high potential for cancer diagnosis and therapy, particularly for tumor imaging and chemotherapy in a synchronous manner.

Intravascular contrast agents in diagnostic applications： Use of red blood cells to improve the lifespan and efficacy of blood pool contrast agents

In medicine, discrimination between pathologies and normal areas is of great importance, and in most cases, such discrimination is made possible by novel imaging technologies. Numerous modalities have been developed to visualize tissue vascularization in cardiovascular diseases or during angiogenic and vasculogenic processes. Here, we report the recent advances in vasculature imaging, providing an overview of the current non-invasive approaches in biomedical diagnostics and potential future strategies for prognostic assessment of vessel diseases, such as aneurysms and coronary artery occlusion leading to myocardial infarction. There are several contrast agents （CAs） available to improve the visibility of specific tissues at the early stage of diseases, allowing for rapid treatment. However, CAs are also hampered by numerous limitations, including rapid diffusion from blood vessels into the interstitial space, toxicity, and low sensitivity. Extravasation from blood vessels leads to a rapid loss of the image. If the contrast medium can fully be confined to the vascular space, high-resolution structural and functional vascular imaging could be obtained. Many scientists have contributed new materials and/or new carrier systems. For example, the use of red blood cells （RBCs） as CA-delivery systems appears to provide a scalable alternative to current procedures that allows adequate vascular imaging. Recognition and removal of CAs from the circulation can be prevented and/or delayed by using RBCs as biomimetic CA-carriers, and this technology should be clinically validated.

From stem cells to red blood cells:how far away from the clinical application?

The generation of red blood cells(RBCs)from stem cells provides a solution for deficiencies in blood transfusion.Currently,primary hematopoietic stem cells,embryonic stem cells and induced pluripotent stem cells have shown the potential to produce fully mature RBCs.Here,we discuss the advantages,induction protocols,progress and possible clinical applications of stem cells in RBC production.

Toxic effects of Litsea elliptica Blume essential oil on red blood cells of Sprague-Dawley rats

Litsea elliptica Blume leaves have been traditionally used as medicinal herbs because of its antimutagenicity,chemopreventative and insecticidal properties. In this study,the toxic effects of L. elliptica essential oil against Sprague-Dawley rat’s red blood cells (RBCs) were evaluated. L. elliptica essential oil was given by oral gavage 5 times per week for 3 treated groups in the doses of 125,250,and 500 mg/(kg body weight),respectively,and the control group received distilled water. Full blood count,RBC osmotic fragility,RBC morphological changes,and RBC membrane lipid were analyzed 28 d after the treatment. Although L. elliptica essential oil administration had significantly different effects on hemoglobin (Hb),mean cell hemoglobin concentration (MCHC),mean cell volume (MCV),and mean cell hemoglobin (MCH) in the experimental groups as compared to the control group (P<0.05),the values were still within the normal range. L. elliptica induced morphological changes of RBC into the form of echinocyte. The percentage of echinocyte increased significantly among the treated groups in a dose-response manner (P<0.001). The concentrations of RBC membrane phospholipids and cholesterol of all treated groups were significantly lower than those of control group (P<0.001). However,the RBC membrane osmotic fragility and total proteins of RBC membrane findings did not differ significantly between control and treated groups (P>0.05). It is concluded that structural changes in the RBC membrane due to L. elliptica essential oil administration did not cause severe membrane damage.

A DLM/FD/IB Method for Simulating Compound Cell Interacting with Red Blood Cells in a Microchannel

In this article, a computational model and related methodologies have been tested for simulating the motion of a malaria infected red blood cell （iRBC for short） in Poiseuille flow at low Reynolds numbers. Besides the deformability of the red blood cell membrane, the migration of a neutrally buoyant particle （used to model the malaria parasite inside the membrane） is another factor to determine the iRBC motion. Typically an iRBC oscillates in a Poiseuille flow due to the competition between these two factors. The interaction of an iRBC and several RBCs in a narrow channel shows that, at lower flow speed, the iRBC can be easily pushed toward the wall and stay there to block the channel. But, at higher flow speed, RBCs and iRBC stay in the central region of the channel since their migrations axe dominated by the motion of the RBC membrane.

Exact Singularity Subtraction from Boundary Integral Equations in Modeling Vesicles and Red Blood Cells

The study of vesicles,capsules and red blood cells(RBCs)under flow is a field of active research,belonging to the general problematic of fluid/structure interactions.Here,we are interested in modeling vesicles,capsules and RBCs using a boundary integral formulation,and focus on exact singularity subtractions of the kernel of the integral equations in 3D.In order to increase the precision of singular and near-singular integration,we propose here a refinement procedure in the vicinity of the pole of the Green-Oseen kernel.The refinement is performed homogeneously everywhere on the source surface in order to reuse the additional quadrature nodes when calculating boundary integrals in multiple target points.We also introduce a multi-level look-up algorithm in order to select the additional quadrature nodes in vicinity of the pole of the Green-Oseen kernel.The expected convergence rate of the proposed algorithm is of order δ(1/N^(2))while the computational complexity is of order δ(N^(2) lnN),where N is the number of degrees of freedom used for surface discretization.Several numerical tests are presented to demonstrate the convergence and the efficiency of the method.