Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Vascular resistance and tissue perfusion may be both affected by impaired vascular function and increased blood viscosity. Little is known about the effects of vascular function on the occurrence of painful vaso-occlusive crises (VOC) in children with sickle cell anemia (SCA). The aim of the present study was to determine which side of the balance (blood viscosity or vascular function) is the most deleterious in SCA and increases the risk for frequent hospitalized VOC. Microvascular function, microcirculatory oxygenation and blood viscosity were determined in a group of 22 SCA children/adolescents at steady state and a group of 13 healthy children/adolescents. Univariate analyses demonstrated blunted microvascular reactivity during local thermal heating test and decreased microcirculatory oxygenation in SCA children compared to controls. Multivariate analysis revealed that increased blood viscosity and decreased microcirculatory oxygenation were independent risk factors of frequent VOC in SCA. In contrast, the level of microvascular dysfunction does not predict VOC rate. In conclusion, increased blood viscosity is usually well supported in healthy individuals where vascular function is not impaired. However, in the context of SCA, microvascular function is impaired and any increase of blood viscosity or decrease in microcirculatory oxygenation would increase the risks for frequent VOC.
ISSN: 1079-9796

hal-01668335
https://hal.univ-antilles.fr/hal-01668335
DOI : 10.1016/j.bcmd.2015.10.005

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Oxidative stress and haemolysis-associated nitric oxide (NO) depletion plays a crucial role in the development of vasculopathy in sickle cell anaemia (SS). However it remains unknown whether oxidative stress and haemolysis levels influence vascular function in patients with sickle haemoglobin C disease (SC). Microvascular response to heat (using Laser Doppler flowmetry on finger), oxidative stress biomarkers, NO metabolites, endothelin-1 and haematological parameters were compared between patients with SS and SC. Vascular function, oxidative and nitrosative markers were also measured in healthy (AA) children. SS and SC had increased plasma advanced oxidation protein products (AOPP), malondialdehyde, plasma antioxidant activities and NO end products, compared to AA. SC had lower catalase activity compared to AA and SS. Haemolytic rate, glutathione peroxidase and nitrotyrosine concentrations were significantly increased in children with SS compared to SC and AA. SS and SC had impaired microvascular reactivity compared to AA. In SS, the plateau phase of the response to local thermal heating was negatively associated with nitrotyrosine and AOPP. No association between vascular function parameters and oxidative stress markers was observed in SC. Mild haemolysis in SC, compared to SS, may limit oxidative and nitrosative stress and could explain the better preserved microvascular function in this group.
ISSN: 0007-1048

hal-01668314
https://hal.univ-antilles.fr/hal-01668314
DOI : 10.1111/bjh.14693

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
Résumé : International audience
107e Congrès français d'urologie
Paris, France

hal-01128018
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01128018
DOI : 10.1016/j.purol.2013.08.056

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Little is known about the impact of blood rheology on the occurrence of retinopathy in sickle cell disease (SCD). Fifty-nine adult SCD patients in steady-state condition participated to the study: 32 with homozygous SCD (sickle cell anemia; SCA) and 27 with sickle cell hemoglobin-C disease (SCC). The patients underwent retinal examination and were categorized according to the classification of Goldberg: 1) no retinopathy (group 1), 2) non-proliferative or proliferative stage I-II retinopathy (group 2) and 3) proliferative stage III-IV-V retinopathy (group 3). Hematological and hemorheological (whole blood viscosity, RBC deformability and aggregation properties) measurements were performed for each patient. In the whole SCD group (SCA + SCC patients) and in SCC patients, the group 3 had higher platelets count than group 2 but the difference between group 3 and group 1 did not reach statistical significance. No difference was observed for the other parameters between the three groups. SCC patients from the group 3 exhibited higher whole blood viscosity than SCC patients from the group 1. No significant difference was observed between the three groups in SCA patients. This study revealed that severe sickle proliferative retinopathy is associated with blood hyperviscosity in SCC patients but not in SCA patients.
ISSN: 1386-0291

inserm-00849032
http://www.hal.inserm.fr/inserm-00849032
http://www.hal.inserm.fr/inserm-00849032/document
http://www.hal.inserm.fr/inserm-00849032/file/inserm-00849032.pdf
DOI : 10.3233/CH-2012-1622

Éditeur(s) : HAL CCSD Ferrata Storti Foundation
Résumé : International audience
The aim of the study was to determine the factors associated with resting and exercise-induced hemoglobin oxygen desaturation. The well-established six-minute walk test was conducted in 107 sickle cell children (50 with sickle hemoglobin C disease and 57 with sickle cell anemia) at steady state. Hemoglobin oxygen saturation was measured before and immediately after the six-minute walk test. Blood samples were obtained on the same day to measure hematologic and hemorheological parameters. Exercise-induced hemoglobin oxygen desaturation was defined as a drop in hemoglobin oxygen saturation of 3% or more at the end of the six-minute walk test compared to resting levels. No children with sickle hemoglobin C disease, but approximately 50% of children with sickle cell anemia showed mild or moderate oxygen desaturation at rest, which was independently associated with the percentage of reticulocytes. Exercise-induced hemoglobin oxygen desaturation was observed in 18% of children with sickle hemoglobin C disease and 34% of children with sickle cell anemia, and was independently associated with the six-minute walk test, acute chest syndrome rate and the strength of red blood cell aggregates in children with sickle cell anemia. No association was found in children with sickle hemoglobin C disease between exercise-induced hemoglobin oxygen desaturation and the measured parameters. Hemoglobin oxygen desaturation at rest was common in children with sickle cell anemia but not in children with sickle hemoglobin C disease, and was mainly associated with greater hemolysis. Physiological strain during exercise and red blood cell aggregation properties may predict the occurrence of exercise-induced hemoglobin oxygen desaturation in children with sickle cell anemia.
ISSN: 0390-6078

inserm-00838989
http://www.hal.inserm.fr/inserm-00838989
http://www.hal.inserm.fr/inserm-00838989/document
http://www.hal.inserm.fr/inserm-00838989/file/Waltz_et_al._Ferrata_Storti_Foundation.pdf
DOI : 10.3324/haematol.2013.083576

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
A decreased global autonomic nervous system (ANS) activity and increased sympathetic activation in patients with sickle cell anemia (SCA) seem to worsen the clinical severity and could play a role in the pathophysiology of the disease, notably by triggering vaso-occlusive crises. Because exercise challenges the ANS activity in the general population, we sought to determine whether a short (,15 min) and progressive moderate exercise session conducted until the first ventilatory threshold had an effect on the ANS activity of a group of SCA patients and a group of healthy individuals (CONT group). Temporal and spectral analyses of the nocturnal heart rate variability were performed before and on the 3 nights following the exercise session. Standard deviation of all normal RR intervals (SDNN), total power, low frequencies (LF) and high frequencies powers (HF) were lower but LF/HF was higher in SCA patients than in the CONT group. Moderate exercise did not modify ANS activity in both groups. In addition, no adverse clinical events occurred during the entire protocol. These results imply that this kind of short and moderate exercise is not detrimental for SCA patients.
ISSN: 1932-6203

hal-01136725
https://hal.univ-antilles.fr/hal-01136725
https://hal.univ-antilles.fr/hal-01136725/document
https://hal.univ-antilles.fr/hal-01136725/file/Hedreville%20et%20al.%20-%202014%20-%20Acute%20moderate%20exercise%20does%20not%20further%20alter%20the%20autonomic%20nervous%20system%20activity%20in%20patients%20with%20sick%282%29.pdf
DOI : 10.1371/journal.pone.0095563

Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
ISSN: 0006-4971

inserm-00919490
http://www.hal.inserm.fr/inserm-00919490
http://www.hal.inserm.fr/inserm-00919490/document
http://www.hal.inserm.fr/inserm-00919490/file/2013_Lemonne_-_Does_increased_red_blood_cell_deformability_raise_the_risk_for_osteonecrosis_in_sickle_cell_anemia.pdf
http://www.hal.inserm.fr/inserm-00919490/file/inserm-00919490_edited.pdf

Éditeur(s) : HAL CCSD
Résumé : Travaux Pratiques de Biochimie, IUT 2e année. Mise en place d'un réacteur enzymatique. Beta galactosidase. Transformation de l'oNPG en orthonitrophénol et galactose.
https://medihal.archives-ouvertes.fr/medihal-00459238
Terre Sainte, France

Droits : http://creativecommons.org/licenses/by-nc/
medihal-00459238
https://medihal.archives-ouvertes.fr/medihal-00459238
https://medihal.archives-ouvertes.fr/medihal-00459238/image
https://medihal.archives-ouvertes.fr/medihal-00459238/file/tp_biochimie_iut05.jpg

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
MR and MDHD contributed equally to this work. Summary Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence , we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxi-dase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil-and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.
ISSN: 0007-1048

inserm-01476067
http://www.hal.inserm.fr/inserm-01476067
http://www.hal.inserm.fr/inserm-01476067/document
http://www.hal.inserm.fr/inserm-01476067/file/2016%2C%20Hierso%20-%20Exacerbation%20of%20oxidative%20stress%20during%20sickle%20vaso-occlusive%20crisis.pdf
DOI : 10.1111/bjh.14476

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Sickle cell anemia (SCA) and hemoglobin SC (HbSC) disease are the two most common forms of sickle cell disease (SCD), a frequent hemoglobinopathy which exhibits a highly variable clinical course. Although high levels of microparticles (MPs) have been consistently reported in SCA and evidence of their harmful impact on the SCA complication occurrences have been provided, no data on MP pattern in HbSC patients has been reported so far. In this study, we determined and compared the MP patterns of 84 HbSC and 96 SCA children, all at steady-state, using flow cytometry. Most of circulating MPs were derived from platelets (PLTs) and red blood cells (RBCs) in the two SCD syndromes. Moreover, we showed that HbSC patients exhibited lower blood concentration of total MPs compared to SCA patients, resulting mainly from a decrease of MP levels originated from RBCs and to a lesser extent from PLTs. We did not detect any association between blood MP concentrations and the occurrence of painful vaso-occlusive crises, acute chest syndrome and pulmonary hyper-tension in both patient groups. We also demonstrated for the first time, that whatever the considered genotype, RBC-derived MPs exhibited higher externalized phosphatidylserine level and were larger than PLT-derived MPs.
ISSN: 1932-6203

hal-01668322
https://hal.univ-antilles.fr/hal-01668322
https://hal.univ-antilles.fr/hal-01668322/document
https://hal.univ-antilles.fr/hal-01668322/file/journal.pone.0177397.pdf
DOI : 10.1371/journal.pone.0177397

Éditeur(s) : HAL CCSD
Résumé : Travaux Pratiques de Biochimie, IUT 2e année. Mise en place d'un réacteur enzymatique. Beta galactosidase. Transformation de l'oNPG en orthonitrophénol et galactose.
https://medihal.archives-ouvertes.fr/medihal-00459241
Terre Sainte, France

Droits : http://creativecommons.org/licenses/by-nc/
medihal-00459241
https://medihal.archives-ouvertes.fr/medihal-00459241
https://medihal.archives-ouvertes.fr/medihal-00459241/image
https://medihal.archives-ouvertes.fr/medihal-00459241/file/tp_biochimie_iut08.jpg

Éditeur(s) : HAL CCSD
Résumé : Travaux Pratiques de Biochimie, IUT 2e année. Mise en place d'un réacteur enzymatique. Beta galactosidase. Transformation de l'oNPG en orthonitrophénol et galactose.
https://medihal.archives-ouvertes.fr/medihal-00459245
Terre Sainte, France

Droits : http://creativecommons.org/licenses/by-nc/
medihal-00459245
https://medihal.archives-ouvertes.fr/medihal-00459245
https://medihal.archives-ouvertes.fr/medihal-00459245/image
https://medihal.archives-ouvertes.fr/medihal-00459245/file/tp_biochimie_iut12.jpg

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Hemorheological abnormalities have been well characterized in sickle cell disease (SCD) and seem to modulate the clinical severity [1]. For instance, increased blood viscosity raises the risk for frequent vaso-occlusive crisis (VOC) and increased red blood cell (RBC) aggregates robustness (i.e., RBC disaggregation threshold) enhances the risks for acute chest syndrome (ACS) [2]. Moreover, patients with the most rigid RBCs are characterized by high hemolytic rate, which increases the risks to develop leg ulcers or glomerulopathy [3]. However, except few studies supporting an effect of alpha-thalassemia and oxidative stress [1] on RBC rheological properties of SCD patients, very few experiments focused on the genetic and cellular factors modulating blood rheology in this disease.
ISSN: 1079-9796

hal-01263890
https://hal.archives-ouvertes.fr/hal-01263890
https://hal.archives-ouvertes.fr/hal-01263890/document
https://hal.archives-ouvertes.fr/hal-01263890/file/Ferdinand%20et%20al.%20eNOS%20and%20RBC%20rheology%20in%20SCD_BCMD.pdf
PUBMED : 26142331

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: The RH blood group system has many RHCE variant alleles that have arisen through gene conversion or nucleotide changes. Two probands, with red blood cells (RBCs) that were D+C+E-c+(w) e+ were sent to our laboratories to resolve the weak c expression. STUDY DESIGN AND METHODS: Hemagglutination tests were performed by automated and manual procedures. Genomic DNA analysis was performed by sequencing of Exons 1 to 10 of RHCE and RHD. RESULTS: The probands' RBCs did not react with standard monoclonal anti-E reagents from Bio-Rad, Diagast, DiaMed, Immucor, Ortho, and Quotient. The RBCs reacted variably with anti-c reagents from Diagast, DiaMed, Immucor, or Ortho and did not react with the Quotient anti-c reagent. Surprisingly, sequencing results of RHCE showed the presence of C/G at Position 676 (E/e polymorphism) and the association of the E polymorphism with a 734T>C transition in Exon 5 of the RHCE, encoding a Leu245Pro amino acid substitution in the mature RhcE polypeptide. Replacement of leucine 245 by proline in the eighth transmembrane domain of the RhcE protein may have a steric effect on the protein such that most anti-E reagents do not bind and the interaction between anti-c and c antigen is also affected. CONCLUSION: We report a novel RHCE*cE allele, RHCE*cE734C, which was assigned the provisional ISBT allele name RHCE*cE.14 or RHCE*03.14. It was found in two probands whose RBCs had weakened c expression and typed E- with conventional anti-E reagents. These data, once again, highlight the fact that the genotype does not always reflect the phenotype.
ISSN: 0041-1132

hal-00839022
https://hal.archives-ouvertes.fr/hal-00839022
DOI : 10.1111/j.1537-2995.2012.03860.x
PUBMED : 22958092

Éditeur(s) : HAL CCSD
Résumé : Travaux Pratiques de Biochimie, IUT 2e année. Mise en place d'un réacteur enzymatique. Beta galactosidase. Transformation de l'oNPG en orthonitrophénol et galactose.
https://medihal.archives-ouvertes.fr/medihal-00459243
Terre Sainte, France

Droits : http://creativecommons.org/licenses/by-nc/
medihal-00459243
https://medihal.archives-ouvertes.fr/medihal-00459243
https://medihal.archives-ouvertes.fr/medihal-00459243/image
https://medihal.archives-ouvertes.fr/medihal-00459243/file/tp_biochimie_iut10.jpg

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
The hematocrit-to-viscosity ratio (HVR) has been widely used has an estimate of red blood cell (RBC) oxygen transport effectiveness into the microvasculature or as an oxygen delivery index. However, no study investigated the possibility of HVR to truly reflect RBC oxygen transport effectiveness or to be an oxygen delivery index. We measured blood viscosity at high shear rate (225 s-1), hematocrit, HVR, as well as the microvascular oxyhemoglobin saturation (TOI; tissue oxygen index) by spatial resolved near-infrared spectroscopy (NIRS) at cerebral and muscle levels in three population known to have various degrees of hemorheological abnormalities: healthy subjects (AA), patients with sickle cell SC disease (SC) characterized by moderate anemia and patients with sickle cell anemia (SS) marked by severe anemia. At both the cerebral and muscle level, HVR was positively correlated with TOI (r = 0.28; p = 0.03 and r = 0.38; p = 0.003, at the cerebral and muscle level, respectively). These findings suggest that HVR probably play a key role in blood flow and hemodynamic regulation in the microvasculature, hence modulating the amount of oxygen available for tissues. Nevertheless, the strengths of the associations are weak (R2 < 0.50), suggesting that other determinants modulate microvascular blood flow and oxygenation, such as vascular geometry and vasomotor reserve.
ISSN: 1386-0291

inserm-01081701
http://www.hal.inserm.fr/inserm-01081701
http://www.hal.inserm.fr/inserm-01081701/document
http://www.hal.inserm.fr/inserm-01081701/file/2013%2C%20Waltz%20-%20Is%20there%20a%20relationship%20between%20the%20hematocrit-to-viscosity%20ratio%20and%20microvascular%20oxygenation%20in%20brain%20and%20muscle.pdf
PUBMED : 23719422

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

Éditeur(s) : HAL CCSD
Résumé : Travaux Pratiques de Biochimie, IUT 2e année. Mise en place d'un réacteur enzymatique. Beta galactosidase. Transformation de l'oNPG en orthonitrophénol et galactose.
https://medihal.archives-ouvertes.fr/medihal-00459249
Terre Sainte, France

Droits : http://creativecommons.org/licenses/by-nc/
medihal-00459249
https://medihal.archives-ouvertes.fr/medihal-00459249
https://medihal.archives-ouvertes.fr/medihal-00459249/image
https://medihal.archives-ouvertes.fr/medihal-00459249/file/tp_biochimie_iut16.jpg

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
alpha- and beta-spectrins are components of molecular scaffolds located under the lipid bilayer and named membrane skeletons. Disruption of these scaffolds through mutations in spectrins demonstrated that they are involved in the membrane localization or the maintenance of proteins associated with them. The ubiquitous alphaII-spectrin chain bears in its central region a unique domain that is sensitive to several proteases such as calpains or caspases. The conservation of this region in vertebrates suggests that the proteolysis of alphaII-spectrin by these enzymes could be involved in important functions. To assess the role of alphaII-spectrin cleavage in vivo, we generated a murine model in which the exons encoding the region defining this cleavage sensitivity were disrupted by gene targeting. Surprisingly, homozygous mice expressing this mutant alphaII-spectrin appeared healthy, bred normally, and had no histological anomaly. Remarkably, the mutant alphaII-spectrin assembles correctly into the membrane skeleton, thus challenging the notion that this region is required for the stable biogenesis of the membrane skeleton in nonerythroid cells. Our finding also argues against a critical role of this particular alphaII-spectrin cleavage in either major cellular functions or in normal development.
ISSN: 0021-9258

inserm-00284621
http://www.hal.inserm.fr/inserm-00284621
http://www.hal.inserm.fr/inserm-00284621/document
http://www.hal.inserm.fr/inserm-00284621/file/Meary_-_JBC_2007.pdf
PUBMED : 17374614