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) : Neidine Editeurs
Résumé : This article replaces the French program of legal extension of the continental shelf named EXTRAPLAC, interesting in particular the 3 overseas collectivities of the Pacific (New Caledonia, Wallis and Futuna and French Polynesia)” It considers this program in the context of the Convention of the United Nations on the Maritime law. It clarifies the governance system of this program set up by the authorities of the State. A specific chapter clarifies the constraints to be respected to build up the necessary file in respect of the international Committee requirements so said UNO Commission of the Limits of the Continental shelf. The article considers then scenarios presented by 3 territories and state of progress of the three cases, both regarding the acquisition of the useful data and the planning of adequate oceanographic campaigns and structuring the administrative files in front of the UNO in conjunction with the border countries. The article ends finally on the potential extensions, the exploitation rights of mineral and living resources as the obligations which it supposes
Cet article replace le programme français d’extension juridique du plateau continental nommé EXTRAPLAC, intéressant notamment les 3 collectivités d’Outre-Mer du Pacifique (Nouvelle-Calédonie, Wallis et Futuna et Polynésie française) dans le contexte de la Convention des Nations Unies sur le Droit de la Mer. Il explicite le système de gouvernance de ce programme mis en place par les autorités de l’Etat. Un chapitre spécifique explicite les contraintes à respecter pour construire un dossier de demande présentable devant la Commission internationale spécialisée de l’ONU dite Commission des Limites du Plateau Continental. L’article considère ensuite les cas de figures présentés par les 3 territoires et l’état d’avancement des dossiers tant en matière d’acquisition des données utiles et de planification de campagnes océanographiques adéquates que de structuration et de dépôt administratif devant l’ONU en conjonction avec les pays frontaliers. L’article conclue enfin sur les extensions potentielles, les droits d’exploitation de ressources qui peuvent en être tirés comme les obligations que cela suppose.
Taï Kona (2269-7535) (Neidine Editeurs), 2014 , N. 11 , P. 18 - 26

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00217/32820/31254.pdf
http://archimer.ifremer.fr/doc/00217/32820/

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

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
Childhood absence epilepsy is a prototypic form of generalized nonconvulsive epilepsy characterized by short impairments of consciousness concomitant with synchronous and bilateral spike-and-wave discharges in the electroencephalogram. For scientists in this field, the BS/Orl and BR/Orl mouse lines, derived from a genetic selection, constitute an original mouse model "in mirror" of absence epilepsy. The potential of MALDI imaging mass spectrometry (IMS) for the discovery of potential biomarkers is increasingly recognized. Interestingly, statistical analysis tools specifically adapted to IMS data sets and methods for the identification of detected proteins play an essential role. In this study, a new cross-classification comparative design using a combined discrete wavelet transformation-support vector machine classification was developed to discriminate spectra of brain sections of BS/Orl and BR/Orl mice. Nineteen m/z ratios were thus highlighted as potential markers with very high recognition rates (87-99%). Seven of these potential markers were identified using a top-down approach, in particular a fragment of Synapsin-I. This protein is yet suspected to be involved in epilepsy. Immunohistochemistry and Western Blot experiments confirmed the differential expression of Synapsin-I observed by IMS, thus tending to validate our approach. Functional assays are being performed to confirm the involvement of Synapsin-I in the mechanisms underlying childhood absence epilepsy.
ISSN: 1535-3893

hal-00877728
https://hal.archives-ouvertes.fr/hal-00877728
DOI : 10.1021/pr3006974
PUBMED : 22994238

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 1079-9796

hal-01679023
https://hal.univ-antilles.fr/hal-01679023
DOI : 10.1016/j.bcmd.2017.02.001

Éditeur(s) : Elsevier Sci Ltd
Résumé : The eastern Demerara Plateau offshore French Guiana was surveyed in 2003 during the GUYAPLAC cruise (multibeam bathymetry and acoustic imagery, 6-channel seismic reflection and 3.5 kHz echo-sounding). The data show the "post-transform" Cenozoic that the series located on the outer part of the plateau (below c. 2000 m) contain at least twelve stacked mass transport deposits (MTDs) that have recorded a history of large-scale slope failure, as well as two main normal fault sets that provide possible pathways for upward fluid migration through the series, reaching at high as the uppermost MTDs. Seabed data show that the area above the failures is characterized by circular-to-elongate (slope-parallel) depressions interpreted as fluid seeps (pockmarks), some of them have been modified by along slope currents. We suggest that the development of the MTDs to results from the combinaiton of the presence of fluid overpressure at depth the geometry of the margin's deep structure, in particular the existence of a 'free borderlateral border' on the outermost plateau. Our results also emphasise the role of stratigraphic decollements within the Cenozoic series.
Marine And Petroleum Geology (0264-8172) (Elsevier Sci Ltd), 2013-09 , Vol. 46 , P. 287-303

Droits : 2013 Elsevier Ltd. All rights reserved.
http://archimer.ifremer.fr/doc/00157/26850/25316.pdf
DOI:10.1016/j.marpetgeo.2013.06.010
http://archimer.ifremer.fr/doc/00157/26850/

Éditeur(s) : HAL CCSD Federation of American Society of Experimental Biology
Résumé : International audience
The innate immune system is able to detect bacterial LPS through the pattern recognition receptor CD14, which delivers LPS to various TLR signaling complexes that subsequently induce intracellular proinflammatory signaling cascades. In a previous study, we showed the overproduction of the soluble form of CD14 (sCD14) by macrophages from patients with cystic fibrosis (CF). CF is an autosomal recessive disorder that is caused by mutations in the gene that encodes the CFTR protein and is characterized by persistent inflammation. Macrophages play a significant role in the initial stages of this disease due to their inability to act as suppressor cells, leading to chronic inflammation in CF. In this work, we investigated the origin of sCD14 by human macrophages and studied the effect of sCD14 on the production of inflammatory cytokine/chemokine. Our data indicate that sCD14 stimulate proinflammatory cytokine/chemokine production in a manner that is independent of LPS but dependent on the TLR-4/CD14 membrane complex, NF-κB, and the inflammasome. Therefore, sCD14, overproduced by CF macrophages, originates primarily from the endocytosis/exocytosis process and should be considered to be a danger-associated molecular pattern. This elucidation of the origin and inflammation-induced mechanisms associated with sCD14 contributes to our understanding of maintained tissue inflammation.
ISSN: 0892-6638

hal-01526434
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434/file/Soluble%20CD14%20acts%20as%20a%20DAMP%20in%20human-accepted.pdf
PUBMED : 28122919

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
ISSN: 0007-1048

hal-01679026
https://hal.univ-antilles.fr/hal-01679026
DOI : 10.1111/bjh.14693

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 Public Library of Science
Résumé : International audience
BACKGROUND: Early in life, cystic fibrosis (CF) patients are infected with microorganisms. The role of macrophages has largely been underestimated in literature, whereas the focus being mostly on neutrophils and epithelial cells. Macrophages may however play a significant role in the initiating stages of this disease, via an inability to act as a suppressor cell. Yet macrophage dysfunction may be the first step in cascade of events leading to chronic inflammation/infection in CF. Moreover, reports have suggested that CFTR contribute to altered inflammatory response in CF by modification of normal macrophage functions. OBJECTIVES: In order to highlight possible intrinsic macrophage defects due to impaired CFTR, we have studied inflammatory cytokines secretions, recognition of pathogens and phagocytosis in peripheral blood monocyte-derived macrophages from stable adult CF patients and healthy subjects (non-CF). RESULTS: In CF macrophage supernatants, concentrations of sCD14, IL-1β, IL-6, TNF-α and IL-10 were strongly raised. Furthermore expression of CD11b and TLR-5 were sorely decreased on CF macrophages. Beside, no difference was observed for mCD14, CD16, CD64, TLR-4 and TLR1/TLR-2 expressions. Moreover, a strong inhibition of phagocytosis was observed for CF macrophages. Elsewhere CFTR inhibition in non-CF macrophages also led to alterations of phagocytosis function as well as CD11b expression. CONCLUSIONS: Altogether, these findings demonstrate excessive inflammation in CF macrophages, characterized by overproduction of sCD14 and inflammatory cytokines, with decreased expression of CD11b and TLR-5, and impaired phagocytosis. This leads to altered clearance of pathogens and non-resolution of infection by CF macrophages, thereby inducing an exaggerated pro-inflammatory response.
ISSN: 1932-6203

inserm-00872278
http://www.hal.inserm.fr/inserm-00872278
http://www.hal.inserm.fr/inserm-00872278/document
http://www.hal.inserm.fr/inserm-00872278/file/Impaired_Functions.accepted.pdf
DOI : 10.1371/journal.pone.0075667

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
Vascular function has been found to be impaired in patients with sickle cell disease (SCD). The present study investigated the determinants of systemic vascular resistance in two main SCD syndromes in children: sickle cell anemia (SCA) and sickle cell-hemoglobin C disease (SCC). Nitric oxide metabolites (NOx), hematological, hemorheological, and hemodynamical parameters were investigated in 61 children with SCA and 49 children with SCC. While mean arterial pressure was not different between SCA and SCC children, systemic vascular resistance (SVR) was greater in SCC children. Although SVR and blood viscosity (ηb) were not correlated in SCC children, the increase of ηb (+18%) in SCC children compared to SCA children results in a greater mean SVR in this former group. SVR was positively correlated with ηb, hemoglobin (Hb) level and RBC deformability, and negatively with NOx level in SCA children. Multivariate linear regression model showed that both NOx and Hb levels were independently associated with SVR in SCA children. In SCC children, only NOx level was associated with SVR. In conclusion, vascular function of SCC children seems to better cope with higher ηb compared to SCA children. Since the occurrence of vaso-occlusive like complications are less frequent in SCC than in SCA children, this finding suggests a pathophysiological link between the vascular function alteration and these clinical manifestations. In addition, our results suggested that nitric oxide metabolism plays a key role in the regulation of SVR, both in SCA and SCC.
ISSN: 1386-0291

inserm-00849031
http://www.hal.inserm.fr/inserm-00849031
http://www.hal.inserm.fr/inserm-00849031/document
http://www.hal.inserm.fr/inserm-00849031/file/2013_Lamarre_-_Relationships_between_SVR_BR_and_NO_in_children_with_sickle_cell_anemia_or_sickle_cell-hemoglobin_C_disease.pdf
DOI : 10.3233/CH-121661