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1.
Cells ; 13(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38920625

RESUMEN

Envenomation by the Hypnale hypnale in the Western Ghats of India (particularly in the Malabar region of Kerala) and the subcontinent island nation of Sri Lanka is known to inflict devastating mortality and morbidity. Currently, H. hypnale bites in India are devoid of anti-venom regimens. A detailed characterization of the venom is essential to stress the need for therapeutic anti-venom. Notably, the deleterious effects of this venom on human blood cells have largely remained less explored. Therefore, in continuation of our previous study, in the present study, we envisioned investigating the effect of venom on the morphological and physiological properties of red blood cells (RBCs). The venom readily induced deleterious morphological changes and, finally, the aggregation of washed RBCs. The aggregation process was independent of the ROS and the intracellular Ca2+ ion concentration. Confocal and scanning electron microscopy (SEM) images revealed the loss of biconcave morphology and massive cytoskeletal disarray. Crenation or serrated plasma membrane projections were evenly distributed on the surface of the RBCs. The venom did not cause the formation of methemoglobin in washed RBCs but was significantly induced in whole blood. Venom did not affect glucose uptake and Na+/K+ -ATPase activity but inhibited glucose 6 phosphate dehydrogenase activity and decreased the fluidity of the plasma membrane. Venom-induced RBC aggregates exhibited pro-coagulant activity but without affecting platelet aggregation. In pre-incubation or co-treatment studies, none of the bioactive compounds, such as melatonin, curcumin, fisetin, berberine, and quercetin, sugars such as mannose and galactose, and therapeutic polyvalent anti-venoms (Bharat and VINS) were inhibited, whereas only N-acetylcysteine and H. hypnale monovalent anti-venom could inhibit venom-induced deleterious morphological changes and aggregation of RBCs. In post-treatment studies, paradoxically, none of the bioactives and anti-venoms, including N-acetylcysteine and H. hypnale monovalent anti-venom, reversed the venom-induced RBC aggregates.


Asunto(s)
Acetilcisteína , Venenos de Crotálidos , Eritrocitos , Animales , Humanos , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Acetilcisteína/farmacología , Agregación Eritrocitaria/efectos de los fármacos , Antivenenos/farmacología , Calcio/metabolismo , Crotalinae , Especies Reactivas de Oxígeno/metabolismo
2.
J Med Chem ; 67(12): 10425-10435, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38848302

RESUMEN

Hexadimethrine bromide (HB), a synthetic polycationic species, was introduced to clinical practice as a heparin antidote and recently used in gene therapy. However, HB causes various complications such as severe red blood cells (RBCs) aggregation and tissue damage. Herein, we have synthesized a water-soluble quaterphen[3]arene containing multiple sulfonate moieties (SQP3) as a novel macrocyclic neutralizer to reverse HB via direct host-guest complexation. SQP3 exhibited a robust binding affinity toward HB with a considerably high association constant of (4.73 ± 0.61) × 107 M-1. Co-dosed with 1 equiv of SQP3, HB-induced RBCs aggregation and blood coagulation could be effectively reversed. In vitro cellular assay verified that complexation of HB with SQP3 significantly decreased reactive oxygen species production, thereby suppressing cell apoptosis. In vivo neutralization efficacy studies demonstrated that HB/SQP3 was capable of alleviating related organic damage caused by HB and improving the survival rate of HB-treated mice from 20 to 100%.


Asunto(s)
Compuestos Macrocíclicos , Animales , Ratones , Humanos , Compuestos Macrocíclicos/química , Compuestos Macrocíclicos/farmacología , Compuestos Macrocíclicos/síntesis química , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Agregación Eritrocitaria/efectos de los fármacos , Ácidos Sulfónicos/química , Ácidos Sulfónicos/farmacología
3.
Clin Lab ; 70(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38747905

RESUMEN

BACKGROUND: Cold agglutinins (CAs) in blood samples can cause a reversible agglutination of red blood cell (RBC) which result in an incorrect complete blood count (CBC). So, it is important to explore new simple and feasible treatment conditions for clinical work. METHODS: The CAs group included 32 samples with CAs. The parameters of CBC at room temperature or after prewarming at 37°C or 41°C for different time periods were compared. The consistency and correlation of those parameters were analyzed. The morphology of erythrocytes in the CAs group was observed manually. The control group included 45 samples without CAs and prewarmed at 37°C or 41°C for different time periods. The differences were also analyzed. RESULTS: CAs have a significant effect on CBC. After prewarming at 37°C or 41°C the interferences are all corrected. Consider prewarming at 37°C for 120 minutes as the standard procedure. The consistency and correlation analysis showed there was no statistical difference between the results of each subgroup and standard group, except the MCHC of group 41°C 10 minutes. The correlation of parameters between all subgroups and the standard group is satisfied. Microscopic examination showed no RBC aggregation or fragmentation after prewarming at 41°C or 37°C. According to the maximum bias requirements for expert performance in Validation, Verification, and Quality Assurance of Automated Hematology Analyzers, 2nd Edition (CLSI H26-A2), the differences in overall results in control group are negligible. CONCLUSIONS: The 41°C 2 minutes prewarming method is a rapid and effective way for treating samples with CAs. It is an efficient way to obtain more reliable CBC results, without specific instruments.


Asunto(s)
Crioglobulinas , Eritrocitos , Humanos , Crioglobulinas/análisis , Recuento de Células Sanguíneas/métodos , Reproducibilidad de los Resultados , Temperatura , Factores de Tiempo , Agregación Eritrocitaria , Aglutinación
4.
J Trauma Acute Care Surg ; 97(1): 57-64, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38605437

RESUMEN

BACKGROUND: Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane. We hypothesized that RBC aggregation is dependent on the interaction between RBC membrane bound (exposed) PS, extracellular calcium, and tissue factor. METHODS: Human whole blood (WB) was separated into components, including RBCs and platelet-rich plasma (PRP). Whole blood, PRP, and RBCs underwent impedance aggregometry utilizing arachidonic acid (AA), ADP, collagen, calcium, and tissue factor (TF)-based agonists. Red blood cells then underwent impedance aggregometry utilizing combined calcium and TF agonists. Red blood cells were pretreated with Annexin V, a known PS blocking agent, and underwent impedance aggregometry with combined calcium and TF agonists to determine if the mechanism of calcium/TF-induced RBC aggregability is dependent on PS. Red blood cells treated with calcium, TF, calcium+TF, and pre-treated with Annexin V followed by calcium+TF were perfused through an in vitro model of pulmonary microcirculatory flow. RESULTS: Red blood cell aggregation was significantly higher than that of WB and PRP when utilizing a TF agonist, an effect unique to TF. The combination of calcium and TF demonstrated significantly higher RBC aggregation than either agonist alone. Pretreatment with Annexin V resulted in a significantly reduced aggregability of RBC following treatment with TF + calcium. Red blood cells aged to 42 days did not exhibit significant change in aggregation. Exposure to calcium and TF significantly reduced time to thrombosis of RBCs perfused through a pulmonary microcirculatory model. CONCLUSION: Treatment with both TF and calcium synergistically induces RBC aggregation. Phosphatidylserine appears to play an integral role in the TF/calcium-based, age-independent RBC aggregation response. Red blood cells treated with TF + calcium exhibit more rapid thrombus formation in an in vitro model of pulmonary microcirculatory perfusion.


Asunto(s)
Calcio , Eritrocitos , Fosfatidilserinas , Tromboplastina , Trombosis , Humanos , Fosfatidilserinas/metabolismo , Tromboplastina/metabolismo , Calcio/metabolismo , Trombosis/metabolismo , Trombosis/etiología , Eritrocitos/metabolismo , Agregación Eritrocitaria/efectos de los fármacos , Membrana Eritrocítica/metabolismo , Plasma Rico en Plaquetas/metabolismo
5.
Viruses ; 16(4)2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38675987

RESUMEN

Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three-SARS, SARS-CoV-2 and MERS-are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.


Asunto(s)
Microvasos , Polisacáridos , SARS-CoV-2 , Animales , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , Betacoronavirus/metabolismo , COVID-19/metabolismo , COVID-19/virología , Tratamiento Farmacológico de COVID-19 , Células Endoteliales/metabolismo , Células Endoteliales/virología , Agregación Eritrocitaria , Eritrocitos/metabolismo , Eritrocitos/virología , Microvasos/metabolismo , Microvasos/virología , Polisacáridos/metabolismo , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Acoplamiento Viral
6.
Artículo en Ruso | MEDLINE | ID: mdl-38639147

RESUMEN

OBJECTIVE: To study the dynamics of hemorheologic changes and the frequency of early complications of laparoscopic radical hysterectomy in patients with uterine corpus cancer depending on conducting rehabilitation activities in the early postoperative period. MATERIAL AND METHODS: The number of patients with uterine corpus cancer equal 49 (mean age 54.8±2.2 years), divided into 2 comparable groups, was examined: experimental group - 23 patients, who received local magnetotherapy since the first day after surgery for 5-6 days, and control group - 26 patients without physiotherapy. Comparative group included 24 healthy women. The basic rheological parameters, namely blood viscosity at high and low shear rate, hematocrit, erythrocytes' aggregation and deformability, erythrocytes and platelets electrophoretic mobility, were evaluated in all patients initially, on the 1st and 5th days after surgery and in comparison group. RESULTS: There were changes in the rheological properties of the blood before surgery in patients of both groups: increase of blood viscosity, enhancement of aggregation activity of its formed elements, decrease of erythrocytes' deformability properties. The laparoscopic radical hysterectomy was accompanied by the exacerbation of these disorders. The early magnetotherapy in patients reduced hemorheological abnormalities up to the preoperative parameters (p<0.05) for 5 days, as well as reduced the incidence of early postoperative complications by 2.4 times compared to the control group. CONCLUSION: The application of local low-frequency low-intensity magnetotherapy since the first postoperative day allows to reduce the level of postoperative hemorheological abnormalities up to the level of preoperative parameters, as well as the frequency of early postoperative complications.


Asunto(s)
Neoplasias , Humanos , Femenino , Persona de Mediana Edad , Hemorreología , Deformación Eritrocítica , Agregación Eritrocitaria , Complicaciones Posoperatorias
7.
Biorheology ; 59(3-4): 63-80, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38461497

RESUMEN

Leukocytes and platelets must adhere to the wall of blood vessels to carry out their protective functions in inflammation and haemostasis. Recruitment is critically dependent on rheological variables (wall shear rate and stress, red cell aggregation and haematocrit) which affect delivery to the vessel wall as well as velocities and forces experienced there. Leukocyte recruitment is efficient only up to wall shear rates of about 300 s-1 and usually restricted to low-shear post-capillary venules in inflammation. Being smaller, platelets experience lower velocities and shear forces adjacent to the wall and can adhere at much higher shear rates for haemostasis in arteries. In addition, we found quite different effects of variations in haematocrit or red cell aggregation on attachment of neutrophils or platelets, which also assist their separate recruitment in venules or arteries. However, it has become increasingly evident that inflammatory and thrombotic responses may occur together, with platelets promoting the adhesion and activation of neutrophils and monocytes. Indeed, it is 30 years since we demonstrated that platelets could cause neutrophils to aggregate in suspension and, when attached to a surface, could support selectin-mediated rolling of all leukocytes. Thrombin-activated platelets could further induce neutrophil activation and immobilisation. In some conditions, platelets could bind to intact endothelial monolayers and capture neutrophils or monocytes. Subsequently, we found that extracellular vesicles released by activated platelets (PEV) fulfilled similar functions when deposited on surfaces or bound to endothelial cells. In murine models, platelets or PEV could act as bridges for monocytes in inflamed vessels. Thus, leukocytes and platelets are rheologically adapted for their separate functions, while novel thrombo-inflammatory pathways using platelets or PEV may underlie pathogenic leukocyte recruitment.


Asunto(s)
Agregación Eritrocitaria , Adhesividad Plaquetaria , Humanos , Animales , Ratones , Adhesividad Plaquetaria/fisiología , Células Endoteliales , Plaquetas/fisiología , Leucocitos/fisiología , Neutrófilos , Reología , Inflamación/metabolismo , Adhesión Celular , Selectina-P/metabolismo
8.
Sci Rep ; 14(1): 4260, 2024 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383860

RESUMEN

Multiple myeloma (MM) is considered to be one of the hematological malignancies formed by excessive and abnormal proliferation of plasmocytes. Among other parameters, several blood tests are used to diagnose multiple myeloma. The hemorheological profile in multiple myeloma is not widely studied. Hemorheology includes the study of measuring the deformability and aggregation of erythrocytes, blood viscosity, and sedimentation rate. The degree of deformability of blood cells is necessary to maintain proper vital functions. Proper deformability of red blood cells ensures proper blood circulation, tissue oxidation and carbon dioxide uptake. The aim of the study was to compare morphology and blood rheology parameters in patients with MM and healthy individuals. The study included 33 patients with MM, and 33 healthy subjects of the same age. The hematological blood parameters were evaluated using ABX MICROS 60 hematology analyzer. The LORCA Analyzer to study erythrocyte aggregation and deformability. Patients with MM had lower red blood cells count (RBC) (9.11%) (p < 0.001) and half time of total aggregation (T1/2) (94.29%) (p < 0.001) values and higher mean corpuscular volume (MCV) (5.50%) (p < 0.001), aggregation index (AI) (68.60%) (p < 0.001), total extent of aggregation (AMP) (87.92%) (p < 0.001) values than the healthy control group. Aggregation in patients with MM is different compared to healthy individuals. It was observed that the percentage of cell aggregation is almost 50% higher than in the control group. The study of morphology, aggregation and deformability of erythrocytes in patients with suspected MM may be helpful in making clinical decisions.


Asunto(s)
Deformación Eritrocítica , Mieloma Múltiple , Humanos , Hemorreología , Eritrocitos , Agregación Eritrocitaria , Reología , Viscosidad Sanguínea , Sedimentación Sanguínea
9.
Pediatr Res ; 95(5): 1335-1345, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38177250

RESUMEN

BACKGROUND: In the Fontan palliation for single ventricle heart disease (SVHD), pulmonary blood flow is non-pulsatile/passive, low velocity, and low shear, making viscous power loss a critical determinant of cardiac output. The rheologic properties of blood in SVHD patients are essential for understanding and modulating their limited cardiac output and they have not been systematically studied. We hypothesize that viscosity is decreased in single ventricle circulation. METHODS: We evaluated whole blood viscosity, red blood cell (RBC) aggregation, and RBC deformability to evaluate changes in healthy children and SVHD patients. We altered suspending media to understand cellular and plasma differences contributing to rheologic differences. RESULTS: Whole blood viscosity was similar between SVHD and healthy at their native hematocrits, while viscosity was lower at equivalent hematocrits for SVHD patients. RBC deformability is increased, and RBC aggregation is decreased in SVHD patients. Suspending SVHD RBCs in healthy plasma resulted in increased RBC aggregation and suspending healthy RBCs in SVHD plasma resulted in lower RBC aggregation. CONCLUSIONS: Hematocrit corrected blood viscosity is lower in SVHD vs. healthy due to decreased RBC aggregation and higher RBC deformability, a viscous adaptation of blood in patients whose cardiac output is dependent on minimizing viscous power loss. IMPACT: Patients with single ventricle circulation have decreased red blood cell aggregation and increased red blood cell deformability, both of which result in a decrease in blood viscosity across a large shear rate range. Since the unique Fontan circulation has very low-shear and low velocity flow in the pulmonary arteries, blood viscosity plays an increased role in vascular resistance, therefore this work is the first to describe a novel mechanism to target pulmonary vascular resistance as a modifiable risk factor. This is a novel, modifiable risk factor in this patient population.


Asunto(s)
Viscosidad Sanguínea , Agregación Eritrocitaria , Deformación Eritrocítica , Procedimiento de Fontan , Humanos , Niño , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/fisiopatología , Masculino , Femenino , Hematócrito , Corazón Univentricular/cirugía , Corazón Univentricular/fisiopatología , Preescolar , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/anomalías , Gasto Cardíaco , Adolescente , Eritrocitos
10.
Clin Hemorheol Microcirc ; 87(1): 27-37, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38250764

RESUMEN

BACKGROUND: Arteriovenous malformations (AVMs) are vascular anomalies characterized by abnormal shunting between arteries and veins. The progression of the AVMs and their hemodynamic and rheological relations are poorly studied, and there is a lack of a feasible experimental model. OBJECTIVE: To establish a model that cause only minimal micro-rheological alterations, compared to other AV models. METHODS: Sixteen female Sprague Dawley rats were randomly divided into control and AVM groups. End-to-end anastomoses were created between the saphenous veins and arteries to mimic AVM nidus. Hematological and hemorheological parameters were analyzed before surgery and on the 1st, 3rd, 5th, 7th, 9th, and 12th postoperative weeks. RESULTS: Compared to sham-operated Control group the AVM group did not show important alterations in hematological parameters nor in erythrocyte aggregation and deformability. However, slightly increased aggregation and moderately decreased deformability values were found, without significant differences. The changes normalized by the 12th postoperative week. CONCLUSIONS: The presented rat model of a small-caliber AVM created on saphenous vessels does not cause significant micro-rheological changes. The alterations found were most likely related to the acute phase reactions and not to the presence of a small-caliber shunt. The model seems to be suitable for further studies of AVM progression.


Asunto(s)
Malformaciones Arteriovenosas , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Animales , Ratas , Femenino , Malformaciones Arteriovenosas/patología , Vena Safena/patología , Hemorreología , Derivación Arteriovenosa Quirúrgica , Deformación Eritrocítica , Agregación Eritrocitaria
11.
Clin Hemorheol Microcirc ; 86(3): 303-312, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37927250

RESUMEN

Blood microrheology depends on the constituents of blood plasma, the interaction between blood cells resulting in red blood cell (RBC) and platelets aggregation, and adhesion of RBC, platelets and leukocytes to vascular endothelium. The main plasma protein molecule -actuator of RBC aggregation is fibrinogen. In this paper the effect of interaction between the endothelium and RBC at different fibrinogen concentrations on the RBC microrheological properties was investigated in vitro. Laser tweezers were used to measure the RBC-endothelium interaction forces. It was shown for the first time that the interaction forces between RBC and endothelium are comparable with the RBC aggregation forces, they increase with fibrinogen concentration and reach the saturation level of about 4 pN at the concentration of 4 mg/ml. These results are important for better understanding the mechanisms of RBC and endothelium interaction and developing the novel therapeutic protocols of the microrheology correction in different pathologies.


Asunto(s)
Fibrinógeno , Pinzas Ópticas , Células Endoteliales , Eritrocitos , Agregación Eritrocitaria
12.
Clin Hemorheol Microcirc ; 86(1-2): 245-252, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37781797

RESUMEN

The size of body compartments is a determinant of several factors of blood viscosity. Red cell aggregation is proportional to fat mass while hematocrit is proportional to both fat-free mass and abdominal adiposity, but which parts of these body components are involved in this relationship is not known. Segmental bioelectrical impedance analysis (sBIA) provides a possibility to delineate the relationships more precisely between various subdivisions of the body and blood viscosity factors, going farther than preceding studies using non segmental BIA. In this study we investigated in 38 subjects undergoing a standardized breakfast test with mathematical modelling of glucose homeostasis and a segmental bioelectrical impedance analysis (sBIA) the relationships between the various compartments of the body and viscosity factors. Blood and plasma viscosity were measured with the Anton Paar rheometer and analyzed with Quemada's model. The parameters better correlated to hematocrit are fat free mass (r = 0.562) and its two components muscle mass (r = 0.516) and non-muscular fat-free mass (r = 0.452), and also trunk fat mass (r = 0.383) and waist-to hip ratio (r = 0.394). Red cell aggregation measurements were correlated with both truncal and appendicular fat mass (r ranging between 0.603 and 0.728). Weaker correlations of M and M1 are found with waist circumference and hip circumference. This study shows that the correlation between lean mass and hematocrit involves both muscle and non-muscle moieties of lean mass, and that both central and appendicular fat are determinants of red cell aggregation.


Asunto(s)
Viscosidad Sanguínea , Hemorreología , Humanos , Viscosidad Sanguínea/fisiología , Hemorreología/fisiología , Agregación Eritrocitaria/fisiología , Hematócrito , Viscosidad
13.
Clin Hemorheol Microcirc ; 87(1): 39-53, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38143339

RESUMEN

BACKGROUND: Even though cardiovascular stenting is widely used for the treatment of coronary artery disease, information on how it can affect the hematological and hemorheological profile is scarce in the literature. Most of the work on this issue is based on theoretical or computational fluid dynamics models, lacking in-depth in vitro and in vivo experimental verification. OBJECTIVE: This work investigates, in an in vivo setting, the effects of stenting and the implantation time-course on hematological and hemorheological parameters that could potentially compromise the device's functionality and longevity. METHODS: Custom-made self-expanding nitinol stents were implanted in the common carotid artery of male CD1 mice. Whole blood samples were collected from control (non-stented) and stented animals at 5 and 10 weeks post-implantation. Hematological measurements and blood viscosity, red blood cell aggregation, and deformability were performed using standard techniques. RESULTS: Implant-induced changes were observed in some of the hematological and hemorheological indices. Blood viscosity seems to have been negatively affected by an increased hematocrit and reduced RBC deformability, at 10 weeks post-implantation, despite a slight decrease in RBC aggregation. CONCLUSIONS: Although the alterations observed may be the result of the peri-implant inflammatory response, the physiological consequences due to hemorheological changes need to be further investigated.


Asunto(s)
Viscosidad Sanguínea , Hemorreología , Stents , Animales , Ratones , Masculino , Deformación Eritrocítica , Agregación Eritrocitaria , Aleaciones , Hematócrito
14.
Int J Mol Sci ; 24(19)2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37834401

RESUMEN

Several studies have indicated that COVID-19 can lead to alterations in blood rheology, including an increase in red blood cell aggregation. The precise mechanisms behind this phenomenon are not yet fully comprehended. The latest findings suggest that erythrocyte aggregation significantly influences microcirculation, causes the formation of blood clots in blood vessels, and even damages the endothelial glycocalyx, leading to endothelial dysfunction. The focus of this research lies in investigating the cellular factors influencing these changes in aggregation and discussing potential causes and implications in the context of COVID-19 pathophysiology. For this purpose, the aggregation of erythrocytes in a group of 52 patients with COVID-19 pneumonia was examined in a 70 kDa Dextran solution, which eliminates the influence of plasma factors. Using image analysis, the velocities and sizes of the formed aggregates were investigated, determining their porosity. This study showed that the process of erythrocyte aggregation in COVID-19 patients, independent of plasma factors, leads to the formation of more compact, denser, three-dimensional aggregates. These aggregates may be less likely to disperse under circulatory shear stress, increasing the risk of thrombotic events. This study also suggests that cellular aggregation factors can be responsible for the thrombotic disorders observed long after infection, even when plasma factors have normalized. The results and subsequent broad discussion presented in this study can contribute to a better understanding of the potential complications associated with increased erythrocyte aggregation.


Asunto(s)
COVID-19 , Agregación Eritrocitaria , Humanos , Dextranos , Eritrocitos/fisiología , Plasma
15.
Soft Matter ; 19(45): 8717-8728, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37886799

RESUMEN

Homogeneous suspensions of red blood cells (RBCs or erythrocytes) in blood plasma are unstable in the absence of driving forces and form elongated stacks, called rouleaux. These erythrocyte aggregates are often branched porous networks - a feature that existing red blood cell aggregation models and simulations fail to predict exactly. Here we establish that alignment-dependent attractive forces in a system of dimers can precisely generate branched structures similar to RBC aggregates observed under a microscope. Our simulations consistently predict that the growth rate of typical mean rouleau size remains sub-linear - a hallmark from past studies - which we also confirm by deriving a reaction kernel taking into account appropriate collision cross-section, approach velocities, and an area-dependent sticking probability. The system exhibits unique features such as the existence of percolated and/or single giant cluster states, multiple coexisting mass-size scalings, and transition to a branched phase upon fine-tuning of model parameters. Upon decreasing the depletion thickness we find that the percolation threshold increases but the morphology of the structures opens up towards an increased degree of branching. Remarkably the system self-organizes to produce a universal power-law size distribution scaling irrespective of the model parameters.


Asunto(s)
Agregación Eritrocitaria , Eritrocitos , Polímeros
16.
Clin Hemorheol Microcirc ; 85(1): 1-12, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37482986

RESUMEN

BACKGROUND: Thalassemia patients have reduced red cell deformability and decreased plasma zinc levels in their blood. OBJECTIVE: This study aimed to evaluate the effects of zinc (Zn) on the hemorheological parameters and antioxidant enzyme activities in ß-thalassemia major (TM) and healthy volunteers (HV). METHODS: Hemorheological parameters were measured using LORCA (laser-assisted optical rotational cell analyzer) after adjusting the hematocrit to 40%. Zinc sulfate (ZnSO4.7H2O) was used for Zn incubation with a concentration of 0.5µg/dl. Oxidative stress and antioxidant status were determined using commercial kits. RESULTS: Data showed that after Zn incubation, EImax, the area under the EI-osmolarity curve (Area), and Omax decreased in TM. However, no significant difference was observed in the osmotic deformability parameters of HV. The increased elongation index was obtained at different shear stresses for TM and HV, and SS1/2 decreased in both groups. The AMP and aggregation index (AI) decreased in TM, and the required time for half of the maximum aggregation (t1/2) increased in HV. However, Zn did not affect oxidative parameters in both groups. CONCLUSIONS: This study showed that Zn incubation increased deformability and decreased aggregation in thalassemic erythrocytes. It means that Zn supplementation will contribute to microcirculation in thalassemia patients.


Asunto(s)
Deformación Eritrocítica , Talasemia beta , Humanos , Talasemia beta/tratamiento farmacológico , Antioxidantes/farmacología , Zinc/farmacología , Agregación Eritrocitaria , Eritrocitos
17.
Clin Hemorheol Microcirc ; 84(4): 369-383, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37334582

RESUMEN

BACKGROUND: Yielding and shear elasticity of blood are merely discussed within the context of hematocrit and erythrocyte aggregation. However, plasma might play a substantial role due its own viscoelasticity. OBJECTIVE: If only erythrocyte aggregation and hematocrit would determine yielding, blood of different species with comparable values would present comparable yield stresses. METHODS: rheometry (SAOS: amplitude and frequency sweep tests; flow curves) of hematocrit-matched samples at 37°C. Brillouin Light Scattering Spectroscopy at 38°C. RESULTS: Yield stress for pig: 20mPa, rat: 18mPa, and human blood: 9mPa. Cow and sheep blood were not in quasi-stationary state supporting the role of erythrocyte aggregation for the development of elasticity and yielding. However, pig and human erythrocytes feature similar aggregability, but yield stress of porcine blood was double. Murine and ruminant erythrocytes both rarely aggregate, but their blood behavior was fundamentally different. Pig plasma was shear-thinning and murine plasma was platelet-enriched, supporting the role of plasma for triggering collective effects and gel-like properties. CONCLUSIONS: Blood behavior near zero shear flow is not based solely on erythrocyte aggregation and hematocrit, but includes the hydrodynamic interaction with plasma. The shear stress required to break down elasticity is not the critical shear stress for dispersing erythrocyte aggregates, but the shear stress required to fracture the entire assembly of blood cells within their intimate embedding.


Asunto(s)
Viscosidad Sanguínea , Agregación Eritrocitaria , Bovinos , Femenino , Humanos , Ratones , Ratas , Ovinos , Animales , Porcinos , Hematócrito , Eritrocitos , Estrés Mecánico
18.
Int J Mol Sci ; 24(10)2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37239851

RESUMEN

Preeclampsia is the leading cause of complicated neonatal adaptation. The present investigation aimed to study the hemorheological factors during the early perinatal period (cord blood, 24 and 72 h after delivery) in newborns of early-onset preeclamptic mothers (n = 13) and healthy neonates (n = 17). Hematocrit, plasma, and whole blood viscosity (WBV), red blood cell (RBC) aggregation, and deformability were investigated. There were no significant differences in hematocrit. WBV was significantly lower in preterm neonates at birth than in the term 24 and 72 h samples. Plasma viscosity was significantly lower in preterm neonates' cord blood than in healthy controls. RBC aggregation parameters were significantly lower in preterm newborns' cord blood than in term neonates' cord blood 24 and 72 h samples. RBC elongation indices were significantly lower in the term group than in preterm neonates 72 h' sample at the high and middle shear stress range. Changes in the hemorheological parameters, especially RBC aggregation properties, refer to better microcirculation of preterm neonates at birth, which could be an adaptation mechanism to the impaired uteroplacental microcirculation in preeclampsia.


Asunto(s)
Viscosidad Sanguínea , Preeclampsia , Embarazo , Femenino , Recién Nacido , Humanos , Eritrocitos , Hematócrito , Índices de Eritrocitos , Agregación Eritrocitaria
19.
Sci Rep ; 13(1): 7960, 2023 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-37198390

RESUMEN

Balneotherapy is an effective treatment method in various diseases and commonly used treatment modality among patients with musculoskeletal disorders. Sulfur baths are known for healing properties however effect on rheological properties is unstudied. Thus the aim of our study was to determine the effect of sulfur balneotherapy on hemorheological blood indices. A total of 48 patients with osteoarthritis were enrolled to the study. Blood samples were collected twice, before and after 3-week time period. We evaluated complete blood count, fibrinogen, hs-CRP and blood rheology parameters such as elongation index (EI), half-time of total aggregation (T1/2) and aggregation index (AI) analyzed with the Lorrca Maxis. Mean age of studied cohort was 67 ± 5 years. After sulfur baths WBC count was significantly decreased is studied group (p = 0.021) as well as neutrophile count (p = 0.036). Red blood cell EIs were statistically higher after sulfur baths in shear stress ranging from 8.24 to 60.30 Pa. T1/2 was significantly higher (p = 0.031) and AI lower (p = 0.003) compared to baseline. No significant changes in fibrinogen and hs-CRP were observed. It is the first study that evaluate effect of sulfur balneotherapy on rheologic properties of blood. Sulfur water baths may improve erythrocyte deformability and aggregation parameters.


Asunto(s)
Hemorreología , Osteoartritis , Humanos , Persona de Mediana Edad , Anciano , Baños , Proteína C-Reactiva/farmacología , Deformación Eritrocítica , Viscosidad Sanguínea , Osteoartritis/terapia , Fibrinógeno/análisis , Azufre/farmacología , Agregación Eritrocitaria
20.
J Vis Exp ; (193)2023 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-37036231

RESUMEN

Erythrocyte (or red blood cell) sedimentation rate (ESR) is a physical derived parameter of blood which is often used in routine health checks and medical diagnosis. For instance, in the case of inflammation, a higher ESR is observed due to the associated increase in fibrinogen and other plasma proteins. It was believed that this increase was due to the formation of larger aggregates of red blood cells (RBCs) caused by the increase in fibrinogen. Indeed, fibrinogen is an agent-fostering aggregation of RBCs and in the Stokes regime-assumed to be observed in blood-larger aggregates sediment faster. However, all models of ESR measurements based on this hypothesis require further specific physical assumptions, not required in any other system. Besides, modern studies in the field of colloidal suspensions have established that attractive particles form percolating aggregates (i.e. aggregates as wide as the container). The sedimentation of these colloids then follows a so-called "colloidal gel collapse". Recently, it has been shown that RBCs actually follow the same behavior. This hypothesis also allows to efficiently and analytically model the sedimentation curve of RBCs, from which robust and physically-meaningful descriptors can be extracted. This manuscript describes how to perform such an analysis, and discusses the benefits of this approach.


Asunto(s)
Agregación Eritrocitaria , Hemostáticos , Sedimentación Sanguínea , Fibrinógeno , Eritrocitos/química , Física
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