Erythrocyte Aggregation Research Articles

Effect of Intermittent Hypoxic Training on Selected Biochemical Indicators, Blood Rheological Properties, and Metabolic Activity of Erythrocytes in Rowers.

Simple SummaryRowing is among the oldest sports disciplines. Involving multiple muscle groups, it poses a considerable challenge to athletes and amateurs. To improve training efficiency, the hypoxic method (decreasing arterial oxygen concentration) is sometimes applied. The study determined the effect of 3-week hypoxic training on blood indicators in competitive rowers. The reported findings demonstrated that the phenomenon of hypoxia could be an extremely effective training measure in rowers as it exerted a beneficial impact on the athletes’ performance.The study assessed the effect of 3-week intermittent hypoxic training on blood biochemical indicators (blood morphology, fibrinogen), blood rheological properties (erythrocyte deformability, aggregation), erythrocyte enzymatic activity (acetylcholinesterase), and maximal oxygen uptake in competitive rowers. Fourteen male rowers were divided into two equal groups: experimental, training on ergometers under normobaric hypoxia (FiO2 = 16.0%), and control, training on ergometers under normoxia (FiO2 = 21%). Fasting blood was taken before and after training. A significant between-group difference in neutrophil levels before training was noted and a significant decrease in white blood cells in the hypoxia group. Both groups exhibited an increase in elongation index. In the normoxia group, a significant increase in erythrocyte aggregation amplitude was revealed. No significant changes occurred in the other biochemical indicators or those evaluating erythrocyte metabolic activity. Normobaric hypoxia increased erythrocyte deformability, improving blood rheological properties. Maximal oxygen uptake significantly increased only in the experimental group.

Hemorheological Alterations and Physical Activity

Elucidating the complex processes that determine the ability of the human body to adapt to specific intense training programs is critical to improving athletic performance in elite athletes. The present work aims to describe the main hemorheological changes as a result of physical exercises of different intensity, frequency, duration and modes of loading. Sport and physical exertion induce a hemorheological response of different nature and degree, structured in the present paper as follows: erythrocyte aggregation; change in the concentration of basic plasma components; changes in blood flow; changes in blood volume; changes in the endothelial cells of the vascular walls; changes in blood pressure; changes resulting from tissue hypoxia; interacting, different in nature hemorheological consequences. The studied and described original models of hemorheological response can contribute to a more successful adaptation of the training programs—In order to improve the health status of the participants and to optimize the sports form of the elite athletes. Physical loads of different frequencies, intensities and durations induce a different hemorheological response in athletes. The effect of “regular, moderate and properly dosed physical activity” during training is also strictly individual. This fact suggests approaching the training regime of each elite athlete personally, practicing specific to his preparation, well-chosen, balanced physical exercises. This will help to achieve the so-called state of hemorheological fitness. Extensive future research is needed to elucidate the cellular, tissue and molecular mechanism of hemorheological changes in blood, blood cells, and blood plasma. It is essential to study the vascular characteristics and biomechanical properties of blood under physical loads with different regimes and variable parameters, taking into account the individual, professional, biological and mechanical profile of each athlete.

Erythrocyte aggregation in sudden flow arrest is linked to hyperthermia, hypoxemia, and band 3 availability

BackgroundErythrocyte aggregation is a phenomenon that is commonly found in several pathological disease states: stroke, myocardial infarction, thermal burn injury, and COVID‐19. Erythrocyte aggregation is characterized by rouleaux, closely packed stacks of cells, forming three‐dimensional structures. Healthy blood flow monodisperses the red blood cells (RBCs) throughout the vasculature; however, in select pathological conditions, involving hyperthermia and hypoxemia, rouleaux formation remains and results in occlusion of microvessels with decreased perfusion. ObjectivesOur objective is to address the kinetics of rouleaux formation with sudden cessation of flow in variable temperature and oxygen conditions. MethodsRBCs used in this in vitro system were obtained from healthy human donors. Using a vertical stop‐flow system aligned with a microscope, images were acquired and analyzed for increased variation in grayscale to indicate increased aggregation. The onset of aggregation after sudden cessation of flow was determined at proscribed temperatures (37–49°C) and oxygen (0%, 10%), and in the presence and absence of 4, 4′‐Diisothiocyano‐2,2′‐stilbenedisulfonic acid (DIDS). Both autologous and homologous plasma were tested. ResultsRBCs in autologous plasma aggregate faster and with a higher magnitude with both hyperthermia and hypoxemia. Preventing deoxyhemoglobin from binding to band 3 with DIDS (dissociates the cytoskeleton from the membrane) fully blocks aggregation. Further, RBC aggregation magnitude is greater in autologous plasma. ConclusionsWe show that the C‐terminal domain of band 3 plays a pivotal role in RBC aggregation. Further, aggregation is enhanced by hyperthermia and hypoxemia.

DISTURBANCES IN BLOOD RHEOLOGICAL PROPERTIES DURING PHENYLHYDRAZINE INTOXICATION AND THEIR CORRECTION WITH HYBRID MACROMOLECULAR COMPOUNDS IN RATS

A single administration of phenylhydrazine at a dose of 50 mg/kg led to a decrease in hematocrit, impaired aggregation and deformability of erythrocytes, which manifested itself in a decrease in the efficiency of oxygen delivery to tissues. Hybrid macromolecular compounds (10 mg/kg intravenously daily for 4 days) attenuated hemorheological parameters disturbances and increased the efficiency of oxygen delivery to tissues.

The Effect of the Enteral Homeostasis Correction Program on the Hemorheological Pattern in Acute Poisoning With Corrosive Substances

Background poisonings with corrosive substances in russia retains a high proportion among acute exotoxemias. They are accompanied by severe homeostasis disorders with changes in hemorheological pattern in particular.Aim of study To evaluate the effect of the enteral correction of homeostasis (ech) on the hemorheological patterns in patients with acute poisoning with corrosive substances.Material and methods Patients with chemical burns of the mucous membrane of the esophagus of the 2nd-3rd degree and stomach of the 2nd-3rd degree who were treated at the n.v. sklifosovsky research institute for emergency medicine in 2017–2021 were examined. In 73 patients, ech was performed (study group), and 35 patients received standard treatment (comparison group). Indicators of hemorheological status were examined on the 1st, 3rd and 5th days in the course of ongoing therapy, as well as before and after intestinal lavage in patients of the study group. Statistical data analysis was carried out using the statistica 10 software package (statsoft, inc., usa).Results The first stage of ech, characterized by the use of intestinal lavage, has no negative effect on hematocrit, plasma viscosity and erythrocyte aggregation indices.The use of a glucosated enteral solution led to a decrease in plasma viscosity under normal hematocrit conditions at all follow-up periods. In patients of both groups, there was a decrease in blood viscoelasticity under conditions of high shear potential at all stages of the study, which indicates violations of the deformability of red blood cells. This process is more significant in individuals of the comparison group. The conducted studies have shown that standard treatment and ech for poisoning with corrosive substances have a corrective effect on the hemorheological profile aimed at stabilizing blood circulation, however, according to a number of indicators, the effect of ech is more pronounced.Conclusion The program of enteral correction of homeostasis and standard treatment for poisoning with corrosive substances have a unidirectional effect on the indicators of the hemorheological pattern. In cases of application of the enteral homeostasis correction program, the outstripping improvement of the majority of the studied hemorheological parameters is seen.

Description and validation of a new, simple, easy-to handle, point-of-care technique for measuring erythrocyte aggregation kinetics

Erythrocyte aggregation (EA) is a physiological process by which erythrocytes reversibly stick together within the blood vessels. EA plays a major role in blood viscosity in vivo, thereby impacting blood flow to organs. EA is no doubt greatly important in both physiological and pathophysiological conditions, but the studies its importance calls for are complicated by the lack of a reliable and easy way to measure it. We have developed a new point-of-care technique which can very specifically measure EA initial kinetics (EAK) in 20 s directly on blood samples routinely collected in tubes commonly used in clinical settings. We present the results of the validation studies of this EAK test: A mono-exponential curve explains 99% of EAK variance. EAK is normally distributed in healthy individuals, with an interindividual 15% coefficient of variation and is stable for least one hour after blood collection. Intraindividual coefficient of variation is 2.6%. EA can now be easily measured in any clinical setting.

Dark -Field Microscopic Analysis on the Blood of 1,006 Symptomatic Persons After Anti-COVID mRNA Injections from Pfizer/BioNtech or Moderna

The use of dark-field microscopic analysis of fresh peripheral blood on a slide was once widespread in medicine, allowing a first and immediate assessment of the state of health of the corpuscular components of the blood. In the present study we analyzed with a dark-field optical microscope the peripheral blood drop from 1,006 symptomatic subjects after inoculation with an mRNA injection (Pfizer/BioNTech or Moderna), starting from March 2021. There were 948 subjects (94% of the total sample) whose blood showed aggregation of erythrocytes and the presence of particles of various shapes and sizes of unclear origin one month after the mRNA inoculation. In 12 subjects, blood was examined with the same method before vaccination, showing a perfectly normal hematological distribution. The alterations found after the inoculation of the mRNA injections further reinforce the suspicion that the modifications were due to the so-called “vaccines” themselves. We report 4 clinical cases, chosen as representative of the entire case series. Further studies are needed to define the exact nature of the particles found in the blood and to identify possible solutions to the problems they are evidently causing.

Effect of a Dexamethasone Implant on Rheological Blood Parameters in Patients Treated for Retinal Vein Thrombosis.

PurposeTo assess the effect of the prolonged-release dexamethasone implant (Ozurdex) in patients with retinal venous thrombosis on blood rheological parameters and evaluate the impact on morphological and functional parameters.MethodsProspective cross-sectional study involved 35 subjects treated with central retinal vein and vein branch occlusion with intravitreal dexamethasone implant and 35 healthy subjects in control group. Hematocrit, blood and plasma viscosity, erythrocyte aggregation amplitude (EAA), index (EAI), aggregation half-life time (EAT1/2), and erythrocyte deformability (ED) were evaluated. The best-corrected visual acuity (BCVA), central retinal thickness (CRT) and visual field (VF) were examined. All the parameters were examined at the baseline, 7 and 30 days after the treatment. The results were analyzed with correlation and regression and compared to the baseline values.ResultsIn the studied group, three hemorheological parameters improved as early as on the 7th day after the drug administration, and this improvement remained at a similar level on the 30th day. The EAA increased by 21.26% on day 7 and by 19.78% on day 30, the EAI decreased by 10.55% on day 7 and by 9.14% on day 30 and the EAT1/2 time increased by 38.50% on day 7 and by 31.02% on day 30. On day 7, the BCVA was improved by 1 row, CRT was reduced by 170.77 µm (24.49%), and the VF was improved by 9.8 dB (49.92%) compared to baseline parameters. On day 30, the BCVA was improved by three rows, CRT reduced by 244.68 µm (35.09%), and VF improved by 12.09 dB (61.59%).ConclusionThe intravitreal dexamethasone implant used in treating macular oedema in patients with RVO has a statistically significant effect on some rheological parameters of blood, reduction of CRT and clinical improvement in BCVA and VF.

Dual functions of discoidinolysin, a cholesterol-dependent cytolysin with N-terminal discoidin domain produced from Streptococcus mitis strain Nm-76

ABSTRACT Background Some strains of Streptococcus mitis exhibit β-hemolysis due to the β-hemolytic activity of cholesterol-dependent cytolysin (CDC). Recently, a gene encoding an atypical lectinolysin-related CDC was found in S. mitis strain Nm-76. However, the product of this gene remains uncharacterized. We aimed to characterize this atypical CDC and its molecular functions and contribution to the pathogenicity of S. mitis strain Nm-76. Methods Phylogenetic analysis of the CDC gene was conducted based on the web-deposited information. The molecular characteristics of CDC were investigated using a gene-deletion mutant strain and recombinant proteins expressed in Escherichia coli. Results The gene encoding CDC found in Nm-76 and its homolog are distributed among many S. mitis strains. This CDC is phylogenetically different from other previously characterized CDCs, such as S. mitis-derived human platelet aggregation factor (Sm-hPAF)/lectinolysin and mitilysin. Because this CDC possesses an additional N-terminal domain, including a discoidin motif, it was termed discoidinolysin (DLY). In addition to the preferential lysis of human cells, DLY displayed N-terminal domain-dependent facilitation of human erythrocyte aggregation and intercellular associations between human cells. Conclusion DLY functions as a hemolysin/cytolysin and erythrocyte aggregation/intercellular association molecule. This dual-function DLY could be an additional virulence factor in S. mitis.

Rheological parameters as prognostic factors in blood loss

The aim of the work was to study the rheological status in experimental blood loss of varying severity. The experiments were carried out on out bred male rats. De-pending on the severity of blood loss, the animals were divided into subgroups. In each subgroup, the erythrocyte aggregation index, erythrocyte membrane deformability index, and blood plasma viscosity were measured. As a result of statistical data processing, it was found that in case of blood loss of any severity, erythrocyte aggregation plays a leading role, followed by the blood viscosity parameter, and changes in membrane deformability are significant only in the decompensatory phase. Thus, it is once again emphasized that with blood loss, the presence of a persistent, starting from the first stage, changes in the rheological status, which mainly depends on the profile of erythrocyte aggregation. These experimental data, coupled with changes in the viscosity and membrane deformability of erythrocytes in the later stages of blood loss, lead to the idea of a careful use of the mass of erythrocytes for the treatment of critical conditions caused by blood loss. Continuation of experimental studies and translation of their findings into clinical medicine will most likely im-prove treatment tactics and increase its effectiveness in the treatment of patients with hemorrhagic shock.

Sex-differential downregulation of methotrexate on plasma viscosity and whole blood viscosity in psoriasis.

Psoriasis is associated with an increased risk for cardiovascular disease (CVD). Methotrexate (MTX) is often used as a first-line system therapy and there is a need to determine its effect on whole blood viscosity (WBV) and plasma viscosity (PV) in psoriasis.METHODSA prospective, single-center, interventional study with a total of 111 psoriatic patients who received MTX therapy from October 22, 2018, to December 28, 2019, and 111 age- and sex-matched healthy controls. Changes in WBV, PV, blood counts, liver and renal function were evaluated.RESULTSPsoriatic patients had significantly higher levels of WBV and relative viscosity (RV) at low shear rate (LSR), erythrocyte aggregation index (EAI), and PV than sex and age-matched healthy controls. PV was positively correlated with erythrocyte sedimentation rate (ESR), ESR was positively correlated with high sensitive C-reactive protein (hCRP). But only hCRP was positively associated with psoriasis area severity index (PASI) score. MTX significantly decreased the levels of PV, ESR, hCRP, and blood pressure (BP) in male patients, and the level of WBV in female patients. Sex-specific downregulation of MTX on WBV, PV, hCRP, and BP, indicating that the effect of MTX on the risk of cardiovascular disease was related with sex.

Structural and functional changes in erythrocytes associated with the development of thrombosis and disorders of hemostasis

The data of clinical and experimental studies of the last decade force us to reconsider the role of red blood cells in the development of thrombosis and disorders of the hemostasis system. This area is of particular relevance during the COVID-19 pandemic. The purpose of the review is to present data on the structural and functional changes in erythrocytes, on changes in their number associated with the development of thrombosis and hemostasis disorders, including in patients with coronavirus infection. The article presents the results of scientific research devoted to the study of morphological and functional changes in red blood cells that affect hemostasis and thrombosis. These changes include erythrocyte number or hematocrit (which modulates blood rheology through blood viscosity) and qualitative changes such as deformability, erythrocyte aggregation, expression of adhesive proteins and phosphatidylserine, release of extracellular microvesicles, hemolysis, piezo receptor status, modulation of nitric oxide bioavailability. Changes in the parameters of erythrocytes that occur during blood storage are shown, with possible thrombotic consequences during blood transfusion. The most recent research concerns changes in red blood parameters during SARS-CoV-2 infection that are associated with the development of thrombosis: virus attachment and amplification of viral proteins in erythropoiesis progenitor cells; activation of stress erythropoiesis with an increase in nuclear erythrocyte cell percentage up to 42 %; activation of the processes of oxidation of the protein band 3 with its excessive cleavage, oxidation and cleavage of the alpha-chain of spectrin, ankyrin; changes in the lipid architecture of the membrane and a decrease in the activity of erythrocyte antioxidants, which mediate disturbances in cell deformability and impaired ATP release; reducing the ability of red blood cells to secrete nitric oxide; decrease in the level of sphingolipids of the erythrocyte membrane; excessive production of microvesicles with tissue factor; an increase in erythrocyte rigidity with impaired release of intraerythrocyte nitric oxide due to SARS-CoV-2 virus attacking the hemoglobin 1-beta chain and porphyrin capture with potential heme inhibition; an increase on the surface of erythrocytes expression of activated complement components C3b and C4d, immunoglobulin IgG, which worsens cell deformability; attachment of erythrocytes through the Toll-like receptor 9 to neutrophil extracellular traps, which contributes to thrombosis; increased presentation of phosphatidylcholine on erythrocyte membranes, which facilitates the assembly of the tenase and prothrombinase complexes, contributing to the production of thrombin, an increase in intracellular calcium levels with stimulation of the formation of microvesicles with prothrombotic potential. The presented data indicate a significant role of changes in erythrocyte parameters in the development of hemostasis disorders, especially during the COVID-19 pandemic, which makes red blood cells a target for therapy and suggests a change in the emphasis of management tactics for patients with thrombosis.

A rapid and accurate method for estimating the erythrocyte sedimentation rate using a hematocrit-corrected optical aggregation index.

Although both the erythrocyte sedimentation rate (ESR) and optically measured erythrocyte aggregation parameters are affected by the hematocrit, this interaction is not considered by the method used to estimate ESR that considers aggregation parameters. In this study, we investigated the relationship between the ESR obtained by the Westergren method and that obtained with an aggregation parameter, namely, the aggregation index (AI) of multiple hematocrit values and fibrinogen-spiked samples with an analysis time of 5–60 s, and attempted to develop a rapid and accurate ESR estimation method. The AIs obtained from 5- and 10-s optical measurements with a fixed hematocrit were highly correlated with the erythrocyte sedimentation velocity. Furthermore, the rate of the AI increase with an increasing hematocrit was not significantly affected by the fibrinogen concentration at these measurement times. On the basis of these results, we defined the hematocrit-corrected aggregation index (HAI). The exponential function of the HAI obtained from the 5-s measurement agreed well with the sedimentation velocity calculated to eliminate the effect of hindered settling, and the HAI and hematocrit could be used to calculate the time constant of the sedimentation curve with a linear regression equation. The ESR value at 1 h was calculated based on the modified Stokes’ law and the HAI obtained from the 5-s measurement and showed an excellent correlation (R = 0.966) with the ESR value obtained by the Westergren method over a wide range of hematocrit and fibrinogen concentrations.

ERYTHROCYTES AGGREGABILITY AND INTRACARDIAC HEMODYNAMICS IN PATIENTS WITH ATRIAL FIBRILLATION

According to the World Health Organization the morbidity of atrial fibrillations is 1-2% of the general population, which is extremely high number due to the severity of the disease. The frequency of morbidity will increase by about 2.5 times (1). Namely, the unfavorable epidemiological picture of atrial fibrillation makes the project relevant. There are numerous studies, although intracardiac hemodynamics and hemorheologycal parameters and their role in the course of atrial fibrillation have not been studied; We have studied the hemorheological profile in patients with atrial fibrillation. Changes of rheological parameters and hemodynamics were assessed against the background of rhythm disturbances. We examined 50 patients (women-22, men - 28, the average age of 65±10) and 20 healthy volunteers. We have studied the Index of the Erythrocytes aggregability, which is the area of aggregated erythrocytes divided by the full area of the erythrocytes. These new innovative methods “Georgian Technique” is created by Georgian scientists and they are famous in the world as direct, numeral and exact [G. Mchedlishvili, 2004; N. Maeda, 2010; M. Mantskava M., 2011]. Also, all patients the studies: ECG, ECHOcardioscopy was performed. After statistical processing of the material, it was found that erythrocytes aggregability is highly impaired in patients with permanent and persistent forms of atrial fibrillation. Mean value of EAI is 41.7 ± 10.4 compared to the control group, where the average EAI value is within 25.6 ± 1.2. The Index of erythrocytes aggregability (EAI) are significantly increased in inverse proportion to the decrease of the left ventricular ejection fraction. A negative correlation was revealed between the Index of erythrocytes aggregation and the left ventricular ejection fraction (R=0.4); According to the obtained data, changes of rheological parameters deepen in the wake of disruption of intracardiac hemodynamics; This confirms the notion that a small blood vessel is the "target" in the case of atrial fibrillation. From hemodynamic mechanisms rheology plays an important role. They are determinants of hemodynamic processes in the body (2).

Panax Notoginseng Saponins Combined with Dual Antiplatelet Drugs Potentiates Anti-Thrombotic Effect with Alleviated Gastric Injury in A Carotid Artery Thrombosis Rat Model

ObjectiveTo observe the combination effects of Panax notoginseng saponins (PNS)and dual antiplatelet drugs (DAPT), and to explore the mechanism via cyclooxygenase /prostaglandin pathway. MethodsRight carotid artery thrombosis was induced in Wistar rats by infiltration with 70% FeCl3, and the animals were randomly divided into sham group, model group, DAPT group and PNS + DAPT group, intragastrically treated for 4 weeks. The cerebral pia mater microcirculation was observed in vivo after anesthetizing by anatomical microscope. The wet weight of carotid artery thrombosis was measured. Gastric mucosal injury was observed by hematoxylin and eosin staining. Platelet aggregation rate was detected with adenosine diphosphate -induced turbidimetry. Platelet CD62p expression was detected by flow cytometry. Concentrations of 6-Ketoprostaglandin F1 alpha, prostaglandin E2 in gastric mucosa and thromboxane B2, 6-Ketoprostaglandin F1 alpha, tissue plasminogen activator, plasminogen activator inhibitor, and fibrin fragment D in the plasma were measured by radioimmunoassay. ResultsPNS and DAPT increased the blood flow volume of cerebral pia mater and decreased erythrocyte aggregation and leukocyte adhesion of model rats. Compared to DAPT, PNS and DAPT further reduced the weight of carotid artery thrombosis with enhanced inhibition of platelet aggregation, increased tissue plasminogen activator levels and decreased fibrin fragment D levels. PNS and DAPT alleviated gastric injury induced by dual antiplatelet drugs and upregulated the expression of 6-Ketoprostaglandin F1 alpha in the gastric mucosa compared with DAPT. ConclusionsPNS combined with DAPT increased anti-thrombosis effects of DAPT and mitigated DAPT-related gastric injury. The underlying mechanisms may be associated with enhanced antiplatelet aggregation and activation of the fibrinolytic system and up-regulation of 6-Ketoprostaglandin F1 alpha expression in gastric mucosa.

Hierarchical data visualization of experimental erythrocyte aggregation employing cross correlation and optical flow applications

Appraisal of microvascular erythrocyte velocity as well as aggregation are critical features of hemorheological assessment. Examination of erythrocyte velocity-aggregate characteristics is critical in assessing disorders associated with coagulopathy. Microvascular erythrocyte velocity can be assessed using various methodologic approaches; however, the shared assessment of erythrocyte velocity and aggregation has not been well described. The purpose of this study therefore is to examine three independent erythrocyte assessment strategies with and without experimentally induced aggregation in order to elucidate appropriate analytic strategy for combined velocity/aggregation assessment applicable to in-vivo capillaroscopy. We employed a hierarchical microfluidic model combined with Bland-Altman analysis to examine agreement between three methodologies to assess erythrocyte velocity appropriate for interpretation of cinematography of in-vivo microvascular hemorheology. We utilized optical and manual techniques as well as a technique which we term transversal temporal cross-correlation (TTC) to observe and measure both erythrocyte velocity and aggregation. In general, optical, manual and TTC agree in estimation of velocity at relatively low flow rate, however with an increase in infusion rate the optical flow method yielded the velocity estimates that were lower than the TTC and manual velocity estimates. We suggest that this difference was due to the fact that slower moving particles close to the channel wall were better illuminated than faster particles deeper in the channel which affected the optical flow analysis. Combined velocity/aggregation appraisal using TTC provides an efficient approach for estimating erythrocyte aggregation appropriate for in-vivo applications. We demonstrated that the optical flow and TTC analyses can be used to estimate erythrocyte velocity and aggregation both in ex-vivo microfluidics laboratory experiments as well as in-vivo recordings. The simplicity of TTC method may be advantageous for developing velocity estimate methods to be used in the clinic. The trade-off is that TTC estimation cannot capture features of the flow based on optical flow analysis of individually tracked particles.

Effects of biomechanical properties of blood on surface tension-driven flows in superhydrophilic channels

Surface tension-driven microfluidic flows offer low-cost solutions for blood diagnostics due to the pump-less flow handling. Knowledge of the influence of the biomechanical properties of blood on such flows is key to design such devices; however, a systematic examination of that influence is lacking in the literature. We report on the effects of specific hemorheological factors for flows in a superhydrophilic microchannel. Whole human blood and erythrocyte suspensions in phosphate buffer and dextran solutions were tested. Heat-treated counterparts of the aforementioned samples were produced to alter the deformability of the cells. The flow of the samples was imaged and characterized using micro-particle image velocimetry and tracking techniques to probe the effects of hematocrit, and erythrocyte aggregation and deformability. Meniscus velocities, velocity profiles in the channel, and local and bulk shear rates were derived. The mean velocity of blood was affected by the increasing sample viscosity and the reduced erythrocyte deformability as expected. The increased erythrocyte aggregation appeared to affect more the shape of the velocity profiles in the normal, compared to the heat-treated samples. Very high shear rates are observed in the early stages of the flow, suggesting high erythrocyte disaggregation, persisting sufficiently strong until the flow reaches the end of the channel.

Uric acid and uric acid/creatinine ratio and their correlations with the hemorheological determinants in subjects with subclinical carotid atherosclerosis.

we have examined the concentration of serum uric acid and the serum uric acid/creatinine ratio as well as their correlations with the main determinants of the hemorheological profile in a group of subjects with subclinical carotid atherosclerosis. we evaluated the concentration of serum uric acid and the serum uric acid/creatine ratio in 43 men and 57 women [median age 66.00 (25)] with subclinical carotid atherosclerosis, subsequently divided according to the number of traditional cardiovascular risk factors and to the insulin resistance degree. serum uric acid, but not the serum uric acid/creatinine ratio, results strongly influenced by the number of cardiovascular risk factors and by the insulin resistance degree. In the whole group and in the subgroups of subclinical carotid atherosclerosis subjects, serum uric acid and serum uric acid/creatinine ratio show significant correlation, besides with whole blood viscosity, with plasma viscosity and erythrocyte aggregation. The influence of the serum uric acid on the erythrocyte aggregability that is a part of the erythrocyte aggregation is to ascribe to the action carried out by serum uric acid on the erythrocyte zeta potential. it is reasonable to think that the treatment of the asymptomatic or symptomatic hyperuricemia with the urate-lowering therapy that reduces the serum uric acid concentration may reflect on the hemorheological profile which role on the atherosclerotic cardiovascular disease is well known.

Transient stress-related hyperviscosity and endothelial dysfunction in Takotsubo syndrome: a time course study.

Takotsubo syndrome (TTS) is an acute and usually reversible heart failure syndrome, frequently associated with emotional or physical stress. Its pathophysiology remains largely unclear, although several mechanisms related to catecholaminergic storm have been proposed. In this study we analyzed during the acute phase of TTS and at follow-up both hemorheological parameters and biomarkers of endothelial damage, whose time course has never been fully explored. In 50 TTS women, we analyzed several hemorheological parameters [whole blood viscosity (WBV) at 0.512s-1 and at 94.5s-1, plasma viscosity (PLV), erythrocyte deformability and aggregation index] as well as biomarkers of endothelial dysfunction [von Willebrand Factor (vWF), Plasminogen activator inhibitor-1 and factor VIII levels] during the acute phase and after a median 6months follow-up. These variables were also assessed in 50 age-matched healthy women. Respect to follow-up, in the acute phase of TTS we observed higher values of white blood cell count, fibrinogen, WBV at low and high shear rates, PLV, erythrocyte aggregation index and lower values of erythrocyte elongation index. Moreover, all biomarkers of endothelial dysfunction resulted significantly higher in the acute phase. During follow-up WBV at 94.5s-1, erythrocyte elongation index and vWF resulted significantly altered with respect to controls. The results of this study confirm the role of hyperviscosity and endothelial dysfunction in TTS pathophysiology. Moreover, they suggest the persistence of alterations of erythrocyte deformability and endothelial dysfunction even beyond the acute phase that could be the target of therapeutic strategies also during follow-up.

Bio-Responsive Carriers for Controlled Delivery of Doxorubicin to Cancer Cells.

The cellular internalization of drug carriers occurs via different endocytic pathways that ultimately involve the endosomes and the lysosomes, organelles where the pH value drops to 6.0 and 5.0, respectively. We aimed to design and characterize pH/temperature-responsive carriers for the effective delivery of the anti-tumoral drug doxorubicin. To this purpose, poly(N-isopropylacrylamide-co-vinylimidazole) was synthesized as an attractive pH/temperature-sensitive copolymer. Microspheres made of this copolymer, loaded with doxorubicin (MS-DXR), disintegrate in monodisperse nanospheres (NS-DXR) under conditions similar to that found in the bloodstream (pH = 7.4, temperature of 36 °C) releasing a small amount of payload. However, in environments that simulate the endosomal and lysosomal conditions, nanospheres solubilize, releasing the entire amount of drug. We followed the NS-DXR internalization using two cancer cell lines, hepatic carcinoma HepG2 cells and lung adenocarcinoma A549 cells. The data showed that NS-DXR are internalized to a greater extent by HepG2 cells than A549 cells, and this correlated with increased cytotoxicity induced by NS-DXR in HepG2 cells compared with A549 cells. Moreover, NS-DXR particles do not cause hemolysis and erythrocytes aggregation. Administered in vivo, NS-DXR localized in the liver and kidneys of mice, and the loading of DXR into NS resulted in the reduced renal clearance of DXR. In conclusion, the newly developed poly(N-isopropylacrylamide-co-vinyl imidazole) particles are biocompatible and may be introduced as carriers for doxorubicin to hepatic tumors.