Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA) but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC-) and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+) - but with no leg ulcers at the time of the study - were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers) and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties). The hematocrit-to-viscosity ratio (HVR), which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels) was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio) may play a role.
ISSN: 1932-6203

inserm-00922105
http://www.hal.inserm.fr/inserm-00922105
http://www.hal.inserm.fr/inserm-00922105/document
http://www.hal.inserm.fr/inserm-00922105/file/2013_Connes_-_Decreased_Hematocrit.pdf
DOI : 10.1371/journal.pone.0079680

Résumé : Nous avons étudié les marqueurs hémorhéologiques, hématologiques et biochimiques chez des sujets drépanocytaires homozygotes SS (HbS/HbS) et hétérozygotes composites SC (HbS/HbC) dans deux cohortes, pédiatriques et adultes, de patients drépanocytaires, et ce, à travers 7 complications récurrentes de la drépanocytose : 2 appartenant au profil hémolytique (l’ulcère de jambes et la glomérulopathie) et 5 appartenant au phénotype visqueux/vaso-occlusif (l’hypertension artérielle, le syndrome thoracique aigu (STA), la crise vaso-occlusive (CVO), la rétinopathie et l’ostéonécrose). Nous avons montré que : 1) une viscosité sanguine et une déformabilité érythrocytaire élevées sont des facteurs de risques de CVO chez les enfants homozygotes ; 2) Une viscosité sanguine élevée est associée à une hypertension artérielle systémique relative chez des adultes SS ; 3) les enfants SC présente une fonction vasculaire mieux préservée que les enfants SS pour faire face à une augmentation de la viscosité sanguine ; 4) les patients adultes SS avec une ostéonécrose présentent une déformabilité érythrocytaire plus élevée que les patients sans ostéonécrose ; 5) une viscosité sanguine élevée est associée à la présence d’une rétinopathie chez les adultes SC mais pas chez les SS ; 6) les patients adultes SS présentant une glomérulopathie ont un taux d’hémolyse élevé, une déformabilité érythrocytaire réduite et des agrégats érythrocytaires très robustes ; 7) les patients adultes SS avec des ulcères de jambes récurrents ont un taux d’hémolyse accru et une déformabilité érythrocytaire réduite. De plus, nos travaux confirment que l’-thalassémie module les propriétés de déformabilité érythrocytaire, mais montrent pour la première fois qu’elle module aussi les propriétés d’agrégation érythrocytaire, et notamment la force des agrégats érythrocytaires. En conclusion, ces travaux permettent de préciser le rôle de la rhéologie sanguine dans un certain nombre de complications de la drépanocytose et d’enrichir le modèle préexistant divisant les complications de la drépanocytose selon 2 phénotypes : hémolytique versus visqueux/vaso-occlusif. Nous montrons pour la première fois que le phénotype hémolytique est caractérisé aussi par des anomalies de la rhéologie du globule rouge : rigidité accrue et agrégats érythrocytaire robustes.
Hemorheological, hemathological, and biochemical marquers of patients with sickle cell anemia (SS) and patients with sickle cell SC disease (SC) were studied in 2 cohorts: children and adults. We focused on 7 recurrent complications: 5 belonging to the viscosity/vaso-occlusion phenotype (systemic hypertension, acute chest syndrome (ACS), vaso-occlusive crisis (VOC), retinopathy and osteonecrosis) and 2 belonging to the hemolytic phenotype (leg ulcer and glomerulopathy). Our results show that 1) high viscosity is associated with increased risk for VOC in SS children; 2) blood viscosity is increased in SS adults with systemic relative hypertension; 3) SC children have preserved vascular function compared to SS children; 4) SS adults with osteonecrosis are characterized by higher red blood cell (RBC) deformability than SS adults without osteonecrosis; 5) high blood viscosity is associated with retinopathy in SC adults but not in SS adults; 6) SS adults affected by glomerulopathy have high hemolytic rate, low RBC deformability and increased RBC aggregates strenght; 7) SS adults with recurrent leg ulcers have high hemolytic rate and reduced RBC deformability. Moreover, our studies shows that alpha-thalassemia modulate RBC deformability and RBC aggregation properties. In conclusion, this work shows for the first time that the hemolytic phenotype is characterized by an abnormal RBC rheology which may play a role in several sickle cell complications.

http://www.theses.fr/2013AGUY0684/document

Éditeur(s) : HAL CCSD
Résumé : Red blood cell hemodynamics influence blood rheology and thus circulatory function. Different authors showed that red blood cells are heterogeneous in blood flow. This heterogeneity could be explained by physical characteristics such as morphology, aggregability and deformability, but also by cellular and molecular environment. All these notions are found in sickle cell disease where sickle red blood cells become more rigid, leading to vascular occlusions, increased with an inflammatory context. In a preceding study, our results showed that velocity heterogeneity allow RBC classification, leading to different RBC sub-groups, using a dynamical approach and flow studies. In order to have a better understanding of the physiological meaning of such an heterogeneity, dynamical velocity experiences have been conducted in the case of normal and sickle red blood cells with different endothelial activations by proinflammatory cytokines, under a constant venular flow. Thus, normal and sickle red blood cells are classified into different sub-groups, showing their heterogeneity. Moreover, sub-population velocities and distribution evolve differently according to vascular state or treatment. These results show that red blood cell velocities and rheology depend on vascular environment and red blood cell morphology. However, the physiological meaning of this behavior should be explained by cellular and molecular effects of such activation.
https://hal.archives-ouvertes.fr/hal-00201461

hal-00201461
https://hal.archives-ouvertes.fr/hal-00201461
https://hal.archives-ouvertes.fr/hal-00201461/document
https://hal.archives-ouvertes.fr/hal-00201461/file/RBCV_Marianne_v1.pdf

Éditeur(s) : HAL CCSD Ferrata Storti Foundation
Résumé : International audience
BACKGROUND: Little is known about the effects of blood rheology on the occurrence of acute chest syndrome and painful vaso-occlusive crises in children with sickle cell anemia and hemoglobin SC disease. DESIGN AND METHODS: To address this issue, steady-state hemorheological profiles (blood viscosity, red blood cell deformability, aggregation properties) and hematologic parameters were assessed in 44 children with sickle cell anemia and 49 children with hemoglobin SC disease (8-16 years old) followed since birth. Clinical charts were retrospectively reviewed to determine prior acute chest syndrome or vaso-occlusive episodes, and rates of these complications were calculated. RESULTS: Multivariate analysis revealed that: 1) a higher steady-state blood viscosity was associated with a higher rate of vaso-occlusive crises in children with sickle cell anemia, but not in children with hemoglobin SC disease; 2) a higher steady-state red blood cell disaggregation threshold was associated with previous history of acute chest syndrome in children with hemoglobin SC disease and boys with sickle cell anemia. CONCLUSIONS: Our results indicate for the first time that the red blood cell aggregation properties may play a role in the pathophysiology of acute chest syndrome in children with hemoglobin SC disease and boys with sickle cell anemia. In addition, whereas greater blood viscosity is associated with a higher rate of vaso-occlusive crises in children with sickle cell anemia, no association was found in children with hemoglobin SC disease, underscoring differences in the etiology of vaso-occlusive crises between sickle cell anemia and hemoglobin SC disease.
ISSN: 0390-6078

inserm-00849038
http://www.hal.inserm.fr/inserm-00849038
http://www.hal.inserm.fr/inserm-00849038/document
http://www.hal.inserm.fr/inserm-00849038/file/inserm-00849038.pdf
DOI : 10.3324/haematol.2012.066670

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Studies performed in the last decades have highlighted the need to better understand the contribution of the endothelium, vascular function, oxidative stress, inflammation, coagulation, hemolysis and vascular adhesion mechanisms to the pathophysiology of acute vaso-occlusive like events and chronic organ damages in sickle cell disease (SCD). Although SCD is a hemorheological disease, a few works focused on the contribution of blood viscosity, plasma viscosity, red blood cell deformability and aggregation in the pathophysiology of SCD. After a brief description of basic hemorheology, the present review focuses on the role of the hemorheological abnormalities in the causation of several SCD complications, mainly in sickle cell anemia and hemoglobin (Hb) SC disease. Several genetic and cellular modulators of blood rheology in SCD are discussed, as well as unresolved questions and perspectives.
ISSN: 0268-960X

hal-01668334
https://hal.univ-antilles.fr/hal-01668334
DOI : 10.1016/j.blre.2015.08.005

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Because of the metabolic changes induced by a physical activity, the hemorheological properties of patients with sickle cell anemia could be further impaired and increase the risks for vaso-occlusive complications. However, few studies suggest that moderate physical activity could be beneficial rather than harmful in patients with sickle cell anemia (SCA). However, the definition of what can be considered as a moderate physical activity in SCA patients is imprecise. The present study tested the effects of a short incremental cycling exercise test conducted until the first ventilatory threshold on different biomarkers. Hematological and hemorheological parameters were compared between 8 patients with SCA and 13 healthy subjects (CONT) before, immediately after the end of the exercise and at 12, 36 and 60 hours after the exercise. We observed no significant hematological or hemorheological alteration induced by the exercise in the two groups. However, the exercise resulted in a delayed improvement of the red blood cell disaggregation threshold at 36 and 60 hrs after exercise in the SCA group which was paralleled to the decrease in the platelet count in this group. The present study suggests that such an exercise might be beneficial for microcirculatory blood flow.
ISSN: 1386-0291

hal-01137567
https://hal.univ-antilles.fr/hal-01137567

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Sickle cell anemia (SCA) is an inherited red blood cells (RBC) disorder characterized by significantly decreased RBC deformability. The present study aimed to assess whether modulation of RBC Nitric Oxide Synthase (RBC-NOS) activation could affect RBC deformability in SCA.Blood of twenty-five SCA patients was treated for 1 hour at 37°C with Phosphate Buffered Saline (PBS) or PBS containing 1% of Dimethylsulfoxyde as control, L-arginine or N(5)-(1-Iminoethyl)-L-ornithine (L-NIO) to directly stimulate or inhibit RBC-NOS, insulin or wortmannin to indirectly stimulate or inhibit RBC-NOS through their effects on the PI3 Kinase/Akt pathway, and sodium nitroprusside (SNP) and 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) as NO donor and NO scavenger, respectively. RBC deformability was measured by ektacytometry at 3 Pa.RBC deformability significantly increased after insulin treatment and significantly decreased after L-NIO and wortmannin incubation. The other conditions did not affect deformability. Significantly increased nitrotyrosine levels, a marker of enhanced free radical generation, were detected by immunohistochemistry in SNP and insulin treated samples.These data suggest that RBC deformability of SCA can be modulated by RBC-NOS activity but also that oxidative stress may impair effectiveness of RBC-NOS produced NO.
ISSN: 1386-0291

hal-01669738
https://hal.univ-antilles.fr/hal-01669738
DOI : 10.3233/CH-162042

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Patients with hemoglobin C disease (CC) usually do not develop severe complications in comparison with individuals with sickle cell anemia (SS) or with sickle cell hemoglobin C disease (SC). The present study compared the hematological, biochemical, hemorheological and clinical characteristics of CC patients to those of SS, SC and healthy individuals (AA). Blood viscosity was measured at 225 s(-1) with a cone plate viscometer. The hematocrit-to-blood viscosity ratio (HVR), i.e. an index of red blood cell (RBC) oxygen transport effectiveness, was calculated. RBC deformability was determined at 30 Pa by ektacytometry, and RBC aggregation properties by syllectometry. CC and SC had higher blood viscosity and lower HVR than AA. Nevertheless, HVR was higher in CC compared to SS and tended to be higher than in SC. The CC group exhibited very rigid hyperchromic RBC compared to the three other groups. RBC aggregation abnormalities were observed in CC: low RBC aggregation index and high RBC aggregates strength. Despite these hemorheological abnormalities, CC never had hospitalized painful vaso-occlusive crisis or acute chest syndrome. In contrast, all of them had splenomegaly. Of note, 2 out of 7 CC developed retinopathy or otologic disorders. Whether the blood hyperviscosity and decreased RBC deformability are responsible for these complications is unknown. The higher oxygen transport effectiveness (i.e., HVR) of CC compared to SS is probably at the origin of the very low risk of medical complication in this population.
ISSN: 1386-0291

hal-01668336
https://hal.univ-antilles.fr/hal-01668336
DOI : 10.3233/CH-141906

Éditeur(s) : HAL CCSD IOS Press
Résumé : The main objectives of the present work were to test the effects of heat stress on blood rheology and to determine whether the responses can change according to the pig breeds. Thirty-six pigs from three pig's lines (n = 12 for each line) with assumed different tolerance to heat stress were compared: Large White (LW, little tolerance), Creole (CR, good tolerance) and LW × CR pigs (produced from a cross between LW and CR lines). In a first period, all pigs were exposed to a 9-d period of thermo-neutral environment (24°C; d-9 to d-1; P0). At the end of P0, six pigs from each line were slaughtered (n = 18). Then in a second period, the remaining pigs (6/breed; n = 18) were exposed to a 5-d period of heat stress (32°C; d + 1 -d + 5; P1) and thereafter slaughtered at d + 5. Rectal and skin temperatures, as well as respiratory rate, were recorded on d-1 and d + 5. At slaughter, blood was sampled for hematological and hemorheological measurements. Heat stress caused a rise of the skin temperature and respiratory rate without any changes in the rectal temperature or on the hematological and hemorheological parameters when all pigs' lines were considered. We observed a pig line effect on blood viscosity at high shear rate (375 s-1) and red blood cell deformability at 30 Pa with CR pigs having lower blood viscosity and higher red blood cell deformability than LW pigs. While the changes of blood viscosity under heat stress did not reach statistical significance in LW and CR lines, blood viscosity (at 375 s-1) increased above the temperate values in the LW × CR line. Red blood cell deformability at 30 Pa was higher in CR pigs exposed to heat stress compared to LW pigs in the same condition. In conclusion, thermal loading caused physiological stress but did not widely change the hematological and hemorheological profiles. Although some blood rheological parameters seem to vary with the pig breeds, the responses to heat stress are very similar.
ISSN: 1386-0291

hal-01210926
https://hal.archives-ouvertes.fr/hal-01210926
DOI : 10.3233/CH-131722
PRODINRA : 286489
PUBMED : 23603327

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
OBJECTIVES:Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown.MATERIALS AND METHODS:Blood viscosity, red blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients.RESULTS:Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age.CONCLUSION:The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01669747
https://hal.univ-antilles.fr/hal-01669747
DOI : 10.1371/journal.pone.0158182
PUBMED : 27355589
PUBMEDCENTRAL : PMC4927160

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The six-minute walk test is a well-established submaximal exercise reflecting the functional status and the clinical severity of sickle cell patients. The aim of the present cross-sectional study was to investigate the biological determinants of the six-minute walk test performance in children with sickle cell anemia. Hematological and hemorheological parameters, pulmonary function and the six-minute walk test performance were determined in 42 children with sickle cell anemia at steady state. The performance during the six-minute walk test was normalized for age, sex and height and expressed as percentage of the predicted six-minute walk distance. We showed that a high level of anemia, a low fetal hemoglobin expression and low red blood cell deformability were independent predictors of a low six-minute walk test performance. This study describes for the first time the impact of blood rheology in the six-minute walk test performance in children with sickle cell anemia.
ISSN: 1932-6203

inserm-00922110
http://www.hal.inserm.fr/inserm-00922110
http://www.hal.inserm.fr/inserm-00922110/document
http://www.hal.inserm.fr/inserm-00922110/file/2013_Waltz_-_Hematological_and_hemorheological_determinants_6_minutes.pdf
DOI : 10.1371/journal.pone.0077830

Éditeur(s) : HAL CCSD
Résumé : International audience
This paper presents a microfluidic system, characterizing the red blood cell (RBC) deformability through its transit time in a microchannel, which dimensions reproducing blood microcirculation capillary. Electrodes are integrated within the microchannel for electrical measurements. The transit time is measured with the electrical blockade produced when the RBC squeezes in the microchannel (d = 5 μm diameter, while the cell diameter is 8 μm). In order todetermine most suitable electrical frequency range for the voltage applied to excitation electrodes, FEM numerical simulation of the bioimpedance is achieved and presented in this paper. We investigated the frequency response of the bioimpedance taking into account the electrode polarization, the dielectric properties of the medium, a single shell model for RBC and finally the RBC position within the microchannel.
Eurosensors
Paris, France

hal-01592142
https://hal.archives-ouvertes.fr/hal-01592142
DOI : 10.3390/proceedings1040517

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Sickle cell anemia (SS) is characterized by a reduced cerebral microvascular oxygen saturation (cerebral TOI), which is not associated with hemoglobin concentration. Cerebral TOI has never been studied in sickle cell-hemoglobin C disease (SC). We focused on the relationships between hemorheological alterations and cerebral TOI in sickle cell patients with no cerebral vasculopathy and on the usefulness of TOI variability to assess the cerebral vasomotion activity. The blood rheological profile, the level of cerebral TOI (spatial resolved spectroscopy) and the cerebral TOI variability, which reflects vasomotion activity, were compared between 20 healthy subjects (AA), 21 SC patients, and 21 SS patients. Cerebral TOI exhibited the following order: AA > SC > SS. The low cerebral TOI in SS patients was related to red blood cell aggregation and deformability properties. The cerebral TOI variability of SS and SC patients was increased above healthy values and vasomotion activity was negatively associated with the reduced cerebral TOI in SS patients. We demonstrated that (1) blood rheology could be involved in the reduced cerebral TOI in SS patients but not in SC patients; (2) vasomotion activity is increased in SS and SC patients to compensate for the reduced cerebral TOI.
ISSN: 0361-8609

inserm-00838966
http://www.hal.inserm.fr/inserm-00838966
http://www.hal.inserm.fr/inserm-00838966/document
http://www.hal.inserm.fr/inserm-00838966/file/2013_Waltz_American_Journalsur Hematology.pdf
DOI : 10.1002/ajh.23318

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Purpose: The aim of this study was to clarify whether exercising in a tropical climate induces blood rheology alterations despite ad libitum hydration. Methods: Hematological, biochemical and hemorheological changes were investigated in young healthy adults (N = 9 men, 20.7 ± 0.8 yrs) after a 10-km race in hot and humid conditions. Subjects' maximal aerobic abilities were tested using a maximal ramp exercise. Blood was sampled at rest (T R), at the end of the race (T Ex), and after 24 hours of recovery (T 24). Ad libitum hydra-tion was allowed during the race. Blood viscosity (b), red blood cell deformability (EI), aggregation (AI) and disaggregation shear rate (␥) were measured. Results: Hematocrit, hemoglobin and plasma concentration of chlorine, sodium and potassium did not change in response to exercise. No functional consequence was observed on RBC deformability since EI remained unchanged. Percentages of echinocytes, schizocytes and stomatocytes remained in the subclinical range at all times. AI, µ and ßb did not present change. Conclusion: Running exercise in tropical climate with ad libitum hydration does not alter the main rheological properties of blood.
ISSN: 1386-0291

hal-01163975
https://hal.univ-antilles.fr/hal-01163975
DOI : 10.3233/CH-2011-1388

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : Heat stress is one of the major limiting factors of production efficiency in the swine industry. The aims of the present study were 1) to observe if hemorheological and hematological parameters could be associated to physiological acclimation during the first days of heat stress exposure and 2) to determine if water restriction could modulate the effect of thermal heat stress on physiological, hematological and hemorheological parameters. Twelve Large White male pigs were divided into an ad libitum and a water restricted group. All pigs were submitted to one week at 24 °C (D-7 to D-1). Then, at D0, temperature was progressively increased until 32 °C and maintained during one week (D1 to D7). We performed daily measurements of water and feed intake. Physiological (i.e., skin temperature, rectal temperature, respiratory rate), hematological and hemorheological parameters were measured on D-6, D-5, D0, D1, D2 and D7. Water restriction had no effect on physiological, hematological and hemorheological parameters. The first days of heat stress caused an increase in the three physiological parameters followed by a reduction of these parameters suggesting a successful acclimation of pigs to heat stress. We showed an increase in hematocrit, red blood cell aggregation and red blood cell aggregation strength during heat stress. Further, we observed an important release of reticulocytes, an increase of red blood cell deformability and a reduction of feed intake and blood viscosity under heat stress. This study suggests that physiological acute adaptation to heat stress is accompanied by large hematological and hemorheological changes.
ISSN: 1932-6203

hal-01210648
https://hal.archives-ouvertes.fr/hal-01210648
DOI : 10.1371/journal.pone.0102537
PRODINRA : 269557
PUBMED : 25013960

Éditeur(s) : HAL CCSD
Résumé : International audience
In this paper we present a microfluidic architecture dedicated to the study of Red Blood Cells (RBCs) deformability in microchannel smaller than the cell shape (biconcave disc of 7-8 μm in diameter) and cell capability to pass through slits separated by a gap value down to 2 μm, acting as a filter. This device is use in the context of RBCs disorders affecting their deformability, which is analysed versus number of cells trapped in the filter. This device can be seen as mimicking the human spleen. Microfabrication of the chip is based on polydimethylsiloxane (PDMS) associated to a two level thick photoresist mould (SU8). One level is used for microfluidic access with a 25 μm thickness towards the studied zone. The second level concerns the mimicking zones where RBCs flow through 5 μm down to 2 μm-wide slits acting like a mechanical filter. This level has a thickness of 5 μm. Devices have been tested on RBCs having specific disorder on their mechanical elasticity in order to validate the design principle. Two cases are presented in this paper: a.) Sickle RBCs inducing cell rigidity at two levels b.) Parasitized RBCs by Plasmodium falciparum. On both cases, we clearly show that deformability of RBCs influences the capability to pass through small slits (down to 2um) and thus is in relation with the pathology stage. This spleen-like microfluidic chip mimicking the RBCs filtering function is a promising tool for the exploration of RBC disorders combined with mechanical alterations.
4th European Conference on Microfluidics
Limerick, Ireland

hal-01113061
https://hal.archives-ouvertes.fr/hal-01113061

Éditeur(s) : HAL CCSD
Résumé : The spectrin-based skeleton is an essential scaffold underlying different lipid bilayers in all animal cells. Spectrins (Sp), as giant extended flexible heterotetramers (αβ)2, constitute the filaments of this network, the nodes of which are cross-linked by actin filaments. The functions of the Sp-based skeleton, which are well defined in red blood cells (required for shape, resistance to shear stress and deformability) are less well understood in non-erythroid cells.The non-erythroid Sp might participate in the establishment and/or the maintenance of specialized membrane subdomains by accumulating integral membrane proteins (such as ionic channels, ionic pumps, receptors and cell adhesion molecules) as revealed by loss of the main non-erythroid β-Sp. However the effect of non-erythroid α-Sp are less well established. In mammals, α-Sp are encoded by two genes: one for αI-Sp mainly expressed in mature erythrocyte, the second one for αII-Sp which is expressed in all nucleated cells.In the pursuit of αII-Sp functions, we have checked the effect of αII-Sp knock down by siRNA melanoma human cell line. Our data revealed that spectrin depletion is associated with i) an arrest of cell cycle at G1 state ii) a loss of cell adhesion in spite of increase in some integrins iii) some modifications of actin organisation.
Le squelette dépendant de la spectrine, localisé sous la bicouche lipidique, est un échafaudage essentiel de toutes les cellules animales. La Spectrine (Sp), structure géante, robuste mais flexible d'hétéro tétramères (αβ)2, constitue les filaments de ce réseau, dont chaque nœud interagit avec des filaments d'actine. Les fonctions du squelette de Sp, qui sont bien définies dans le globule rouge (rôle dans sa forme, dans sa résistance aux forces de cisaillement et dans sa déformabilité) sont moins bien connues dans les cellules non-érythroïdes. La Sp non-érythroïde pourrait participer à l'établissement et/ou au maintien de sous-domaines membranaires spécialisés dans l'accumulation de protéines de membrane (telles que les canaux ioniques, les pompes ioniques, les récepteurs et les molécules d'adhérence) comme nous le font penser les invalidations de la Sp-β non-érythroïde. Cependant le rôle de la Sp-α non-érythroïde est moins bien établi. Chez les mammifères, la Sp-α est codée par deux gènes: un pour Sp-αI, principalement exprimée dans l'érythrocyte mature, le second pour Sp-αII qui est exprimée dans toutes les cellules nucléées. Pour étudier les fonctions de la Sp-αII, nous avons utilisé une approche de SiRNA sur des cellules de mélanome humain. Nos données montrent que la diminution de Sp-αII est associée à I) un arrêt en G1 du cycle cellulaire II) une perte d'adhérence des cellules malgré l'augmentation de quelques intégrines III) des modifications dans l'organisation du réseau d'actine.
https://tel.archives-ouvertes.fr/tel-00377569

Droits : info:eu-repo/semantics/OpenAccess
tel-00377569
https://tel.archives-ouvertes.fr/tel-00377569
https://tel.archives-ouvertes.fr/tel-00377569/document
https://tel.archives-ouvertes.fr/tel-00377569/file/these_210409_entiere.pdf
https://tel.archives-ouvertes.fr/tel-00377569/file/II-Spectrin_Is_Critical_for_Cell_Adhesion_and_Cell_Cycle.PDF

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Objectives To investigate the association between priapism in men with sickle cell anemia (SCA) and hemorheological and hemolytical parameters. Materials and Methods Fifty-eight men with SCA (median age: 38 years) were included; 28 who had experienced priapism at least once during their life (priapism group) and 30 who never experienced this complication (control group). Twenty-two patients were treated with hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC) deformability at 30 Pa (ektacytometry) and RBC aggregation properties (laser backscatter versus time). Blood viscosity was measured at a shear rate of 225 s(-1) using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), total bilirubin (BIL) levels and reticulocyte (RET) percentage) to calculate a hemolytic index. Results Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01), LDH (p = 0.03), RET (p = 0.03) levels and hemolytic indices (p = 0.02). Higher RBC aggregates strength (p = 0.01) and lower RBC deformability (p = 0.005) were observed in patients with priapism compared to controls. After removing the hydroxycarbamide-treated patients, RBC deformability (p = 0.01) and RBC aggregate strength (p = 0.03) were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01) than controls. Conclusion Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability.
ISSN: 1932-6203

hal-01390971
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390971
DOI : 10.1371/journal.pone.0154866
PUBMED : 27145183

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The present study investigated cerebral and muscle hemoglobin oxygen saturation (tissue oxygen index, TOI) in children with sickle cell anemia (SS), sickle cell hemoglobin C disease (SC) and healthy children (AA). TOI was measured by near-infrared spectroscopy (NIRS) and spectral analysis of the TOI variability was used to assess flowmotion and vasomotion. Arterial oxyhemoglobin saturation (SpO2), hemorheological and hematological parameters were also measured in SS and SC children. Both TOI were lower in SS compared to both AA and SC children, with SC exhibiting lower values than AA children. Cerebral vasomotion expressed in absolute values was enhanced in SS compared to AA and SC children. Muscle vasomotion did not differ between the three groups. Hematocrit, SpO2 and red blood cell deformability were positively associated with cerebral TOI in SS children. We demonstrated that 1) cerebral and muscle TOI were markedly decreased in SS children while the decrease of TOI was milder in SC children, 2) cerebral TOI level was associated with several biological markers in SS children only and 3) cerebral vasomotion was enhanced in SS, possibly to counterbalance the effects of chronic cerebral hypoxia.
ISSN: 1079-9796

hal-01668321
https://hal.univ-antilles.fr/hal-01668321
DOI : 10.1016/j.bcmd.2017.03.015

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND:Sickle cell anaemia (SCA) is a severe hereditary haemoglobinopathy characterised by haemorheological abnormalities, which play a role in the occurrence of several acute and chronic clinical complications. While βS -haplotypes and alpha-thalassaemia modulate SCA clinical severity, their effects on blood rheology have been incompletely described. The aim of this study was to test the effects of these genetic modifiers on the haemorheological properties and clinical complication of children with SCA.PROCEDURE:Steady-state haemorheological profile, biological parameters, βS -haplotypes, alpha-globin status, vaso-occlusive crisis (VOC) and acute chest syndrome frequencies were analysed in 128 children (aged 5 to 18 years) with SCA.RESULTS:Patients with alpha-thalassaemia showed increased red blood cell (RBC) deformability and aggregation compared to those without. Median VOC rate was higher in patients with homozygous alpha-thalassaemia compared to those with a normal alpha genotype. Conversely, the haemorheological profile and clinical complications were not influenced by the βS -haplotypes in our study.CONCLUSION:Our results demonstrate that alpha-thalassaemia is associated with higher risk for VOC events in children with SCA, which may be due in part to its effects on RBC deformability and aggregation.
ISSN: 1545-5009

hal-01668317
https://hal.univ-antilles.fr/hal-01668317
DOI : 10.1002/pbc.26455
PUBMED : 28097791