Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: Chronic HCV infection is associated with the development of hepatic fibrosis. The direct role of HCV in the fibrogenic process is unknown. Specifically, whether HCV is able to infect hepatic stellate cells (HSCs) is debated. OBJECTIVE: To assess whether human HSCs are susceptible to HCV infection. DESIGN: We combined a set of original HCV models, including the infectious genotype 2a JFH1 model (HCVcc), retroviral pseudoparticles expressing the folded HCV genotype 1b envelope glycoproteins (HCVpp) and a subgenomic genotype 1b HCV replicon, and two relevant cellular models, primary human HSCs from different patients and the LX-2 cell line, to assess whether HCV can infect/replicate in HSCs. RESULTS: In contrast with the hepatocyte cell line Huh-7, neither infectious HCVcc nor HCVpp infected primary human HSCs or LX-2 cells. The cellular expression of host cellular factors required for HCV entry was high in Huh-7 cells but low in HSCs and LX-2 cells, with the exception of CD81. Finally, replication of a genotype 2a full-length RNA genome and a genotype 1b subgenomic replicon was impaired in primary human HSCs and LX-2 cells, which expressed low levels of cellular factors known to play a key role in the HCV life-cycle, suggesting that human HSCs are not permissive for HCV replication. CONCLUSIONS: Human HSCs are refractory to HCV infection. Both HCV entry and replication are deficient in these cells, regardless of the HCV genotype and origin of the cells. Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process.
ISSN: 0017-5749

hal-01063909
https://hal.archives-ouvertes.fr/hal-01063909
DOI : 10.1136/gutjnl-2013-305634
PUBMED : 25063678

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
'Alarmins' are a group of proteins or molecules that are released from cells during cellular demise to alert the host immune system. Two of them, Interleukin-33 (IL-33) and high-mobility group box-1 (HMGB1), share many similarities of cellular localization, functions and involvement in various inflammatory pathologies including hepatitis. The expressions of IL-33 and HMGB1, and their receptors ST2 and receptor for advanced glycation end products (RAGE), are substantially up-regulated during acute and chronic hepatitis. Recent data evidence a possible protective role of IL-33/ST2 axis during liver injury. A contrast in expression of IL-33 and HMGB1 alarmins were associated with type of hepatocellular death mediated by immune cells or hepato-toxic agents. The massive release of active form of IL-33 from hepatocytes may affect the recruitment and activation of its ST2-positive target immune cells in the liver to confer its alarmin functions. This review highlights the emerging roles of alarmin proteins in various liver pathologies, by focusing on classical HMGB1 and a newly discovered alarmin, the IL-33.
ISSN: 1478-3223

hal-00874209
https://hal.archives-ouvertes.fr/hal-00874209
DOI : 10.1111/j.1478-3231.2012.02802.x
PUBMED : 22530772

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The chronostratigraphy of the lower Miocene deposits of northwestern Sardinia is refined in the Castelsardo Basin. The combination of new 40Ar/39Ar isotopic datings, 19 micropalaeontological datings (calcareous nannofossils, planktonic and large benthic foraminifers) and 16 palaeomagnetic polarity measurements led to a new chronostratigraphic framework. The continental deposits of the first megasequence (Valledoria and Casteldoria members) are possibly Aquitanian. The overlying marine sediments are early Burdigalian (Vaginella depressa Molasse). The marine transgression can be dated to around 19.7 Ma. Marine conditions ceased 18.83 ± 0.13 Ma, the age of the index aerial τ2 ignimbrite. The continental part of the second megasequence (“Lacustre” unit) is early–middle Burdigalian, between 18.8 and 18 Ma. The overlying marine part (Campulandu and Sedini members) is middle–late Burdigalian. The second marine transgression began in the earliest–late Burdigalian, during the Chron C5Dr reversal, at the time of the eustatic Bur 4 event. The Castelsardo basin went through two main extensional tectonic episodes. The first one occurred as the Valledoria Member was deposited and possibly dates back to the Aquitanian. The second one occurred as the uppermost part of the Vaginella depressa Molasse was deposited during the early Burdigalian. The second extensional episode is related to a rapid rotation of Sardinia. Palaeomagnetic results confirm that Corsica and Sardinia acted as a single block which suffered a 28 ± 17° ccw rotation after 19.2 Ma. The Castelsardo basin is held to be an Aquitanian–early Burdigalian intra-arc rift basin that later evolved in a thermally controlled subsident margin of the Ligurian-Provençal Basin during the middle–late Burdigalian.
ISSN: 0031-0182

hal-00498288
https://hal.archives-ouvertes.fr/hal-00498288
DOI : 10.1016/j.palaeo.2010.06.007

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The implication of oxidative stress as primary mechanism inducing doxorubicin (DOX) cardiotoxicity is still questionable as many in vitro studies implied supra-clinical drug doses or unreliable methodologies for reactive oxygen species (ROS) detection. The aim of this study was to clarify whether oxidative stress is involved in compliance with the conditions of clinical use of DOX, and using reliable tools for ROS detection. We examined the cytotoxic mechanisms of 2 μM DOX 1 day after the beginning of the treatment in differentiated H9c2 rat embryonic cardiac cells. Cells were exposed for 2 or 24 h with DOX to mimic a single chronic dosage or to favor accumulation, respectively. We found that apoptosis was prevalent in cells exposed for a short period with DOX: cells showed typical hallmarks as loss of anchorage ability, mitochondrial hyperpolarization followed by the collapse of mitochondrial activity, and nuclear condensation. Increasing the exposure period favored a shift to necrosis as the cells preferentially exhibited early DNA impairment and nuclear swelling. In either case, measuring the fluorescence lifetime of 1-pyrenebutyric acid or the intensities of dihydroethidium or amplex red showed a consistent pattern in ROS production which was a slight increased level far from representative of an oxidative stress. Moreover, pre-treatment with dexrazoxane provided a cytoprotective effect although it failed to detoxify ROS. Our data support that oxidative stress is unlikely to be the primary mechanism of DOX cardiac toxicity in vitro.
ISSN: 0300-8177

hal-01285736
https://hal-univ-perp.archives-ouvertes.fr/hal-01285736
DOI : 10.1007/s11010-016-2653-x

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm) in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households). The GMT for the general population was 47.1 (95% confidence interval (CI): 45.1, 49.2). According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by-sa/
hal-01122215
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215/file/journal.pone.0060127.pdf
PUBMED : 23613718

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study, we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans.
ISSN: 0041-008X

inserm-00872871
http://www.hal.inserm.fr/inserm-00872871
DOI : 10.1016/j.taap.2012.05.004
PUBMED : 22617429

Éditeur(s) : HAL CCSD Publisher : Paris : Baillière [1980-. Latest Publisher : Paris : Elsevier
Résumé : National audience
Pneumocystis jiroveci (anciennement P. carinii) est un champignon opportuniste responsable de pneumopathies chez les patients immunodéprimés. Les pneumocystoses des patients non infectés par le VIH se distinguent des pneumocystoses du sida par des difficultés diagnostiques accrues, et un pronostic plus sombre. Il est donc indispensable de cibler les immunodépressions les plus à risque, qui bénéficieront d’un traitement par triméthoprime-sulfaméthoxazole à faible dose au long cours, très efficace en prophylaxie des pneumocystoses : ainsi, les vascularites des moyens et petits vaisseaux, les hémopathies lymphoïdes B (leucémie lymphoïde chronique ou aiguë, lymphome malin non hodgkinien) et les cancers solides sous corticothérapie prolongée doivent faire envisager cette prophylaxie. À l’inverse, la généralisation de la prophylaxie à l’ensemble des patients porteurs de pathologies inflammatoires sous corticothérapie n’est pas justifiée. La prise en charge des pneumocystoses des patients non infectés par le VIH suit les principes établis pour les pneumocystoses du sida. Le diagnostic de certitude repose sur la mise en évidence de kystes de P. jiroveci sur des prélèvements respiratoires, tandis que la PCR ne permet pas formellement, en 2015, de différencier colonisation et infection. Le traitement repose sur le triméthoprime-sulfaméthoxazole à fortes doses. Par contre, l’intérêt de la corticothérapie adjuvante pour les patients hypoxémiques, parfaitement documenté au cours du sida, est discuté pour les autres immunodépressions, d’autant que les patients sont en général déjà sous corticoïdes au moment du diagnostic de pneumocystose. Celle-ci est cependant préconisée par plusieurs experts et sociétés savantes, compte tenu du bénéfice démontré sur la morbi-mortalité au cours du sida. Abstract Pneumocystis jiroveci (formerly P. carinii) is an opportunistic fungus responsible for pneumonia in immunocompromised patients. Pneumocystosis in non-HIV-infected patients differs from AIDS-associated pneumocystosis in mostly two aspects: diagnosis is more difficult, and prognosis is worse. Hence, efforts should be made to target immunocompromised patients at higher risk of pneumocystosis, so that they are prescribed long-term, low-dose, trimethoprime-sulfamethoxazole, highly effective for pneumocystosis prophylaxis. Patients at highest risk include those with medium and small vessels vasculitis, lymphoproliferative B disorders (chronic or acute lymphocytic leukaemia, non-Hodgkin lymphoma), and solid cancer on long-term corticosteroids. Conversely, widespread use of prophylaxis in all patients carrier of inflammatory diseases on long-term corticosteroids is not warranted. The management of pneumocystosis in non-AIDS immunocompromised patients follows the rules established for AIDS patients. The diagnosis relies on the detection of P. jiroveci cyst on respiratory samples, while PCR does not reliably discriminate infection from colonization, in 2015. High-doses trimethoprim-sulfamethoxazole is, by far, the treatment of choice. The benefit of adjuvant corticosteroid therapy for hypoxic patients, well documented in AIDS patients, has a much lower level of evidence in non-HIV-infected patients, most of them being already on corticosteroid by the time of pneumocystosis diagnosis anyway. However, based on its striking impact on morbi-mortality in AIDS patients, adjuvant corticosteroid is recommended in hypoxic, non-HIV-infected patients with pneumocystosis by many experts and scientific societies
ISSN: 0248-8663

hal-01237080
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237080
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237080/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237080/file/Pneumocystose%20chez%20les%20patients%20immunod%C3%A9prim%C3%A9s%20non%20infect%C3%A9s%20par%20le%20VIH.pdf
DOI : 10.1016/j.revmed.2015.10.002

Éditeur(s) : HAL CCSD
Résumé : International audience
Island barriers are common features along the world coastlines. They have a crucial role in protecting inland and rich lagoonal ecosystems. Erosion and sand transfers on these island barriers during extreme events such as tropical storms or typhoons remain poorly investigated. This work focuses on a multi-scales nalysis (season to decade) of the morphodynamics of Wan-Tzu-Liao sand barrier subjected to extreme waves and sea surges. We combine topographic measurements of the emerged beach at seasonal scale between 2011 to 2012 and long-term (1993-2009) shoreline changes using aerial photographs and satellite images. At the seasonal scale, during Monsoon, the sand was taken from the beach-front and transported seaward outside the study area. During typhoons season, 12 typhoons drove a beach recovery process resulting in a seaward shoreline shift. This annual behavior is discussed in term of roll-over process of the barrier. At the decadal scale, the shoreline changes evidence cross-shore processes in the north part of the barrier and longshore processes in the south. Although the chronic landward migration displays several stages, the strong losses of the barrier area occurs only since 2004 and call into question the general concept of conservation of mass during the roll-over of a barrier.
Revue Paralia, XIIIème Journées Nationales Génie CIvil Génie Côtier
Dunkerque, France

hal-01018203
https://hal.archives-ouvertes.fr/hal-01018203

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 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 Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists
Résumé : International audience
Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags. Extracellular matrix protein production is regulated by a number of cytokines, including IFN-gamma. We have now screened putative polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located in the third intron of the IFN-gamma gene are associated with PPF. The IFN-gamma +2109 A/G polymorphism is associated with a higher risk for developing PPF, whereas the IFN-gamma +3810 G/A polymorphism is associated with less PPF. The polymorphisms result in changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN-gamma mRNA expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on chromosome 6q22-q23, closely linked to the gene encoding the alpha-chain of the IFN-gamma receptor, and low IFN-gamma producers have been shown to have an increased risk of severe PPF. Together, these observations support the view that IFN-gamma expression and subsequent signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni).
ISSN: 0022-1767

Droits : http://creativecommons.org/licenses/by-nc-nd/
hal-01211760
https://hal.archives-ouvertes.fr/hal-01211760
https://hal.archives-ouvertes.fr/hal-01211760/document
https://hal.archives-ouvertes.fr/hal-01211760/file/J%20Immunol-2003-Chevillard-5596-601.pdf
DOI : 10.4049/jimmunol.171.10.5596

Éditeur(s) : HAL CCSD
Résumé : International audience
Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (ATL). Such complications are seen frequently in L.guyanensis infections where patients respond variously to first-line anti-leishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently ,: we reported that a dsRNA virus (LRV1) nested within L.guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyper-inflammatory response. This report investigates the prevalence of LRV1 in human L.guyanensis infection and its effect on treatment efficacy as well as its correlation to symptomatic relapses after the first-line treatment. In our cohort of 75 patients diagnosed with primary-localised ATL, the prevalence of LRV1+ infection was elevated to 58%. All patients infected with LRV1-negative L.guyanensis were cured after one (22/31 i.e.71%) or two (31/31 i.e.100%) doses of pentamidine. Oppositely, 12 out of the 44 LRV1-positive patients presented with persistent infection and symptomatic relapse required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in intra-lesional inflammatory markers. In conclusion, LRV1 status in L.guyanensis infection is significantly predictive (p=0.0009) of first-line treatment failure and symptomatic relapse, and could stand to guide therapeutic choices in ATL
Journal of Infectious Diseases

hal-01175528
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01175528
DOI : 10.1093/infdis/jiv355
PUBMED : 26123564

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
The Société de pneumologie de langue française defines acute exacerbation of chronic obstructive pulmonary disease (AE COPD) as an increase in daily respiratory symptoms, basically duration ≥ 48h or need for treatment adjustment. Etiology of EA COPD are mainly infectious, viral (rhinovirus, influenzae or parainfluenzae virus, coronavirus, adenovirus and respiratory syncytial virus) or bacterial (Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis). Pollutant exposure can also lead to AE COPD, such as NO2, SO2, ozone or particulates (PM10 and PM2.5). In 30% the etiology remains unknown. Differential diagnoses of AE COPD include infectious pneumonia, pneumothorax, acute heart failure and pulmonary embolism. Presences of signs of severity impose hospitalization: signs of respiratory distress, shock, acute confusion but also fragile patients, insufficient home support or absence of response to initial treatment. AE COPD treatments consist on increase in bronchodilators, chest physiotherapy, and antibiotics if sputum is frankly purulent. Systemic corticosteroids should not be systematic.Recommended dose is 0.5 mg/kg on short course (7 days). During hospitalization, oxygen supplementation and thromboprophylaxis could be prescribed. The main interest in noninvasive ventilation is persistent hypercapnia despite optimal medical management. During ambulatory management or hospitalization, clinical assessment at 48-72h is mandatory. L’exacerbation aiguë de bronchopneumopathie chronique obstructive (EA BPCO) représente un événement important dans l’histoire naturelle de la BPCO, notamment en cas d’hospitalisation. Les EA BPCO interviennent dans la gravité et l’évolution de la BPCO ; et leur prévention est un des objectifs principal des traitements de fond.
La Société de pneumologie de langue française définie l’exacerbation aiguë de bronchopneumopathie chronique obstructive (EA BPCO) comme une majoration des symptômes respiratoires au-delà des variations quotidiennes, en pratique, d’une durée ≥ 48h ou justifiant une modification thérapeutique. L’étiologie de ces EA BPCO est principalement infectieuse, virale (rhinovirus, virus influenzae et parainfluenzae, coronavirus, adénovirus et virus respiratoire syncytial) ou bactérienne (principalement Haemophilus influenzae, Streptococcus pneumoniae et Moraxella catarrhalis). Elles peuvent également résulter de l’exposition à certains polluants comme le NO2, le SO2, l’ozone et la pollution particulaire (PM10 et PM2,5). L’étiologie reste indéterminée dans près de 30 % des cas. Les diagnostics différentiels des EA BPCO incluent les pneumopathies infectieuses, les pneumothorax, les poussées d’insuffisance cardiaque et les embolies pulmonaires. La présence de signes de gravité conditionnent l’hospitalisation : signes d’insuffisance respiratoire aiguë, de choc ou de défaillance neurologique, mais aussi en cas de patient fragile, d’absence de soutien familial à domicile ou d’absence de réponse au traitement initial. Le traitement d’une EA BPCO consiste en une majoration des bronchodilatateurs, une kinésithérapie respiratoire, une antibiothérapie en cas d’expectoration franchement purulente.La prescription de corticoïdes systémiques ne doit pas être systématique. La dose recommandée est de 0,5 mg/kg sur une courte période (7 jours). Lors d’une hospitalisation, une oxygénothérapie et une thromboprophylaxie peuvent être prescrite. La ventilation noninvasiveest principalement indiquée en cas de persistance d’une hypercapnie malgré un traitement médical optimal. Que le patient soit pris en charge en ambulatoire ou en hospitalisation, une réévaluation clinique à 48-72h est indispensable.
ISSN: 0755-4982

hal-01117949
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117949
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117949/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117949/file/Prise%20en%20charge%20des%20exacerbations_accepted.pdf
DOI : 10.1016/j.jeurea.2015.02.002

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 Public Library of Science
Résumé : International audience
Millimeter Waves (MMW) will be used in the next-generation of high-speed wireless technologies, especially in future Ultra-Broadband small cells in 5G cellular networks. Therefore, their biocompatibilities must be evaluated prior to their massive deployment. Using a microarray- based approach, we analyzed modifications to the whole genome of a human keratinocyte model that was exposed at 60.4 GHz-MMW at an incident power density (IPD) of 20 mW/cm2 for 3 hours in athermic conditions. No keratinocyte transcriptome modifications were observed. We tested the effects of MMWs on cell metabolism by co-treating MMW-exposed cells with a glycolysis inhibitor, 2-deoxyglucose (2dG, 20 mM for 3 hours), and whole genome expression was evaluated along with the ATP content.We found that the 2dG treatment decreased the cellular ATP content and induced a high modification in the transcriptome (632 coding genes). The affected genes were associated with transcriptional repression, cellular communication and endoplasmic reticulum homeostasis. The MMW/ 2dG co-treatment did not alter the keratinocyte ATP content, but it did slightly alter the transcriptome, which reflected the capacity of MMWto interfere with the bioenergetic stress response. The RT-PCR-based validation confirmed 6 MMW-sensitive genes (SOCS3, SPRY2, TRIB1, FAM46A, CSRNP1 and PPP1R15A) during the 2dG treatment. These 6 genes encoded transcription factors or inhibitors of cytokine pathways, which raised questions regarding the potential impact of long-term or chronic MMW exposure on metabolically stressed cells. © 2016 Soubere Mahamoud et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN: 1932-6203

hal-01367149
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367149
DOI : 10.1371/journal.pone.0160810
PUBMED : 27529420

Éditeur(s) : HAL CCSD Elsevier
Résumé : An integrated magneto-biostratigraphic study, based on calcareous nannofossils and foraminifers, together with the radiometric dating of a volcaniclastic layer found in several outcrops, was carried out on the hemipelagic deposits of the Lindos Bay Formation (LBF) at six localities on the island of Rhodes (Greece). Our highly refined chronostratigraphic framework indicates that the lower and upper lithostratigraphic boundaries of the LBF are diachronous. Associated with the 40Ar/39Ar age determination of 1.85 ± 0.08 Ma for the volcaniclastic layer, our data show that among the investigated outcrops, the Lindos Bay type locality section provides the longest record (1.1 Ma) of the LBF. Hemipelagic deposition occurred continuously from the late Gelasian (∼1.9 Ma) to the late Calabrian (∼0.8 Ma), i.e., from Chrons C2n (Olduvai) to C1r.1r (Matuyama) and from nannofossil Zones CNPL7 to CNPL10. This long record, together with the hemipelagic nature of the deposits, make the Lindos Bay type locality section a unique element in the eastern Mediterranean region, allowing future comparisons with other early Quaternary deep-sea sections available in the central and western Mediterranean regions.
ISSN: 0033-5894

hal-01467764
https://hal.archives-ouvertes.fr/hal-01467764
DOI : 10.1016/j.yqres.2016.05.002

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet.
The journal of biological chemistry

hal-01063926
https://hal.archives-ouvertes.fr/hal-01063926
DOI : 10.1074/jbc.M113.525220

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Hydroxycarbamide (HC) treatment has been shown to improve the clinical course of patients with sickle cell anaemia (SCA), a haemoglobinopathy resulting from a single base substitution in the bêta-globin gene (HBB). SCA is characterized by chronic haemolytic anaemia and recurrent vascular occlusions leading to multisystemic complications. Several beneficial biological effects of HC have been documented (Halsey et al, 2003) but its impact on the concentration of circulating microparticles (MPs), a subtype of extracellular vesicles released from cytoplasmic membrane of activated or apoptotic cells and detected at high levels in sickle plasma, remains controversial (Hebbel et al, 2016). The aim of the present study was to compare the MP pattern in a group of SCA patients treated by HC and followed for 2 years.
ISSN: 0007-1048

hal-01668320
https://hal.univ-antilles.fr/hal-01668320
https://hal.univ-antilles.fr/hal-01668320/document
https://hal.univ-antilles.fr/hal-01668320/file/Garnier%20et%20al%20BJH-2017-00655.pdf
DOI : 10.1111/bjh.14810

Éditeur(s) : HAL CCSD Elsevier [Commercial Publisher]
Résumé : International audience
BACKGROUND: Pneumocystis jiroveci pneumonia in HIV-negative immunocompromised patients is associated with high mortality rates. Although trimethoprim-sulfamethoxazole (TMP-SMX) provides a very effective prophylaxis, pneumocystosis still occurs and may even be emerging, due to sub-optimal characterization of patients most at risk, hence precluding targeted prophylaxis. METHODS: We retrospectively analyzed all cases of documented pneumocystosis in HIV-negative patients admitted in our institution, a referral center in the area, from January 1990 to June 2010, and extracted data on their underlying condition(s). To estimate incidence rates within each condition, we estimated the number of patients followed-up in our area for each condition, by measuring the number of patients admitted with the corresponding international classification diagnostic code, through the national hospital discharge database (PMSI). RESULTS: From 1990 to 2010, 293 cases of pneumocystosis were documented, of whom 154 (52.6%) tested negative for HIV. The main underlying conditions were hematological malignancies (32.5%), solid tumors (18.2%), inflammatory diseases (14.9%), solid organ transplant (12.3%), and vasculitis (9.7%). Estimated incidence rates could be ranked in three categories: i) high risk (incidence rates extgreater 45 cases per 100,000 patient-year): polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis, acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma; ii) intermediate risk (25-45 cases per 100,000 patient-year): Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer; and iii) low risk ( extless 25 cases per 100,000 patient-year): other solid tumors, inflammatory diseases, and Hodgkin lymphoma. CONCLUSIONS: These estimates may be used as a guide to better target pneumocystosis prophylaxis in the groups most at risk.
ISSN: 0002-9343

hal-01063911
https://hal.archives-ouvertes.fr/hal-01063911
https://hal.archives-ouvertes.fr/hal-01063911/document
https://hal.archives-ouvertes.fr/hal-01063911/file/1-s2.0-S0002934314005907-main.pdf
DOI : 10.1016/j.amjmed.2014.07.010

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
A number of men receiving prolonged suppressive HAART still shed HIV in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with SIVmac251 submitted to HAART for 4 months, intensified over the last seven weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen, or in testis, epididymis, seminal vesicles and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens, and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of non-productively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organs infection in long term treated infected individuals. A substantial subset of men receiving prolonged suppressive HAART in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV-infected macaques treated by HAART. We demonstrated that persistent seminal shedding was not linked to poor drug penetration in semen or semen-producing prostate, seminal vesicle, epididymis and testis. We revealed that HAART decreased SIV RNA to various extents in all male genital organs, with the exception of the urethra, in which SIV RNA+ macrophages were observed despite HAART. Importantly also, HAART did not impact SIV DNA levels in the male genital organs. These results suggest that infection of male genital organs, and particularly the urethra, could be involved in the release of virus in semen during HAART.
ISSN: 0022-538X

hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/file/Detection%20of%20SIV%20in%20Semen%2C%20Urethra%2C%20and%20Male%20Reproductive%20Organs%20during%20Efficient%20Highly%20Active%20Antiretroviral%20Therapy.pdf
PUBMEDCENTRAL : PMC4442442