Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Do mild analgesics affect the endocrine system of the human adult testis? SUMMARY ANSWER: Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. WHAT IS KNOWN ALREADY: Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. STUDY DESIGN, SIZE, DURATION: Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10(-4) or 10(-5) M paracetamol, aspirin or indomethacin for 24-48 h. The effect of 10(-5) M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. MAIN RESULTS AND THE ROLE OF CHANCE: The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin only. Our experiments also revealed that mild analgesics display direct anti-PG activity, which varied depending on the drug used, the dose and the duration of exposure. Nevertheless, associations between the alteration of the PG and testosterone profiles were not systematically observed, suggesting that a combination of mechanisms of endocrine disruption is at play. LIMITATIONS, REASONS FOR CAUTION: Our studies were performed in vitro. WIDER IMPLICATIONS OF THE FINDINGS: We provide the first evidence that direct exposure to mild analgesics can result in multiple endocrine disturbances in the human adult testis. Caution, concerning the consumption of mild analgesics by men, should be strengthened, particularly in high-risk population subgroups such as elite athletes.
ISSN: 0268-1161

inserm-00866016
http://www.hal.inserm.fr/inserm-00866016
PUBMED : 23670170
DOI : 10.1093/humrep/det112

Éditeur(s) : HAL CCSD Centers for Disease Control and Prevention
Résumé : International audience
We report 20 cases of extensively drug-resistant tuberculosis managed in France. Treatment was individualized and included bedaquiline and linezolid for most patients and surgery in 8 patients. At last follow-up (22 months), 19 patients had achieved conversion from positive to negative on culture testing. These promising results of comprehensive management obtained in a small series deserve confirmation.
ISSN: 1080-6040

hal-01294307
http://hal.upmc.fr/hal-01294307
http://hal.upmc.fr/hal-01294307/document
http://hal.upmc.fr/hal-01294307/file/15-1130.pdf
DOI : 10.3201/eid2203.151130

Éditeur(s) : HAL CCSD
Résumé : Food-grade dairy propionibacteria release beneficial short chain fatty acids (SCFAs), folic acid and cobalamin. They induce apoptosis via the mitochondrial death pathway. We investigated their synergy with drugs used in gastric and colorectal cancer.Fermented milk containing propionibacteria and SCFAS acetate and propionate, as well as its cell-free supernatant, induced apoptosis in gastric HGT-1 and colic HT-29. Characterization of cells revealed apoptosis induction evidenced by chromatin condensation, DNA laddering, emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet and cytochrome c release. Interestingly, the fermented milk was shown to potentiate the cytotoxic effect of molecules used in cancer chemotherapy, camptothecin and TRAIL (TNF Related Apoptosis Inducing Ligand).These results open new perspectives in the field of colon cancer cells prevention and/or treatment. Such a fermented product, or the propionibacterium alone, may be proposed as a food supplement to enhance the effects of anticancer treatments.
Les bactéries propioniques laitières produisent des acides gras volatils (AGV), acide folique et cobalamine, composés bénéfiques. Elles induisent l’apoptose via la voie mitochondriale. Nous avons recherché leur synergie avec des drogues utilisées dans le cancer gastrique ou colique.Un lait fermenté contenant des bactéries propioniques et les AGVs propionate et acétate a induit l’apoptose de cellules gastriques HGT-1 et coliques HT-29. L’étude des cellules a révélé l’induction de l’apoptose : condensation de la chromatine, fragmentation de l’ADN, l’émergence d’une population subG1, l’externalisation des phosphatidylserines et le relargage du cytochrome c. De manière intéressante, le lait fermenté a potentialisé les effets cytotoxiques de molécules utilisées en chimiothérapie, camptothécine et TRAIL (TNF Related Apoptosis Inducing Ligand).Ces résultats ouvrent de nouvelles perspectives dans le domaine du traitement ou de la prévention des cancers digestifs. Un tel produit fermenté, ou les propionibactéries seules, pourrait être proposé comme supplément alimentaire pour augmenter l’efficacité de traitements anti-cancéreux.
5. Colloque Intenational Molécules & Ingrédients Santé
Quimper, France

hal-01204307
https://hal.archives-ouvertes.fr/hal-01204307
PRODINRA : 261444

Éditeur(s) : HAL CCSD
Résumé : International audience
Decreased frequency of pulmonary exacerbations, mainly related to immunomodulatory effects of macrolide antibiotics, has been demonstrated in bronchiectasis and chronic obstructive pulmonary diseases (COPD). Due to its tolerance, azithromycin is the antibiotic of choice for maintenance therapy at the dose of 250 mg per day or 500 mg × 3 per week (for body weight extgreater55 kg). Maintenance therapy with macrolide could be proposed in selected patients with bronchiectasis or COPD with more than 3 acute exacerbations in the previous year or decreased lung function despite compliance with optimum treatment. The risk of sudden cardiac death with azithromycin is rare and controversial. It should be avoided in patients with a high baseline risk of cardiovascular disease, QT extgreater450 msec, pulse rate extgreater100 bpm and potential drug interactions, particularly those known to cause QT prolongation. It is recommended to search for hearing deficit (audiometry) and sputum culture positive for mycobacteria. Patients must also be aware that it can rapidly lead to macrolide resistance in commensal or pathogenic flora. Follow-up evaluation every 3 month can be proposed with medical history (hearing deficit) and electrocardiography. After one year, the treatment should be stopped in the absence of reduction in the frequency of exacerbations.
Presse Médicale (Paris, France: 1983)

hal-01063927
https://hal.archives-ouvertes.fr/hal-01063927
DOI : 10.1016/j.lpm.2013.08.006

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 Elsevier
Résumé : International audience
ETHNOPHARMACOLOGICAL RELEVANCE: Cutaneous leishmaniasis is a neglected disease with a high incidence in French Guiana, mainly in the middle and upper Oyapock basin, where Amerindian and some Brazilian people live. The main goals of this work were (i) to assess the knowledge about leishmaniasis in the different populations of the middle and upper Oyapock basin, (ii) to study the therapeutic strategies adopted by people affected by leishmaniasis and (iii) to document the use of phytotherapeutic remedies for leishmaniasis. Knowledge, attitudes and practices (K.A.P.) related to this disease and its treatments have been studied according to cultural group and geographical settlement. Within the Wayãpi group, the evolution of the knowledge of phytoremedies over the last 20 years has been characterised by literature-based comparisons. MATERIALS AND METHODS: A total of 144 questionnaires were administered in all the villages of the upper Oyapock and Camopi basins. Correspondence analyses were used for multivariate analysis. Plant species were identified at the Cayenne Herbarium (CAY). RESULTS: The biomedical concept of leishmaniasis correlates well with the Teko and Wayãpi concepts of kalasapa and kalasapau. Although the vector of this disease was not correctly identified, the most commonly cited aetiology (74.5%) was vector-borne, and related epidemiological schemes correlate well with the one encountered in French Guiana. Theoretically and practically, health centres were the most commonly used resource for diagnostic in instances of leishmaniasis infection (65.9%), independently of the patient's cultural group, along with the use of pharmaceutical drugs (85.3%). Pharmaceuticals were commonly utilised despite the frequent (51.5%) use of phytotherapeutic remedies, alone or in combination with drugs. The most cited medicinal plant species for the treatment of leishmaniasis included Eleutherine bulbosa (Mill.) Urb. (Iridaceae, cited 14 times), Euterpe oleracea Mart. (Arecaceae, 9), Cecropia obtusa Trecul (Cecropiaceae, 8), Jatropha curcas L. (Euphorbiaceae, 7), Ceiba pentandra (L.) Gaertn. (Bombacaceae, 6) and Carica papaya L. (Caricaceae, 6). Multiple correspondence analyses demonstrated that the species used in leishmaniasis remedies are more prone to vary by the user's place of residence than by their cultural origin, which indicates that exchange of knowledge about leishmaniasis remedies has occurred across different cultural groups. Literature-based comparisons between the remedies for leishmaniasis used by the Wayãpi during the 1980s showed a striking evolution, both in terms of diversity of species and number of plants used. The large number of species shared with other Guianese groups argues for intercultural exchange and may explain the majority (57.1%) of the newly used species highlighted in our study. CONCLUSIONS: Leishmaniasis is a well-known disease in the studied area. Phytotherapeutic treatments are still in use, although they are not the main source of remedies, and should undergo pharmacological studies to evaluate their potential therapeutic value.
ISSN: 0378-8741

pasteur-00634597
https://hal-riip.archives-ouvertes.fr/pasteur-00634597
DOI : 10.1016/j.jep.2011.07.044
PUBMED : 21816216

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Invasive aspergillosis is a major cause of mortality in allogeneic bone marrow transplant recipients and patients treated for blood malignancies. The diagnostic tools, treatments and preventive strategies, essentially developed for neutropaenic patients, have not been assessed in populations whose immune systems are considered to be competent. Beside the standard picture of chronic Aspergillus infection, the incidence of invasive aspergillosis is increasing in non neutropaenic patients, such as those with chronic lung diseases or systemic disease treated with long-term immunosuppressive drugs and solid organ transplant recipients. This study reviews the specific features of invasive aspergillosis in non neutropaenic subjects (NNS) and discusses the value of the diagnostic tools and treatment in this population. A better understanding of the pathophysiology and the epidemiological characteristics of invasive aspergillosis would provide a means of adapting the staging and classification of the disease for NNS. Invasive aspergillosis is under diagnosed in NNS who may already be colonised when they receive immunosuppressive treatment; this can lead to an adverse outcome in patients who are considered to be a moderate risk population.
ISSN: 0761-8425

hal-01118185
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118185
DOI : 10.1016/j.rmr.2010.01.004
PUBMED : 20965392

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Reliable molecular typing tools are required for a better understanding of the molecular epidemiology of Plasmodium vivax. The genes msp3a and msp1_block5 are highly polymorphic and have been used as markers in many P. vivax population studies. These markers were used to assess the genetic diversity of P. vivax strains from French Guiana (South America) and to develop a molecular typing protocol. METHODS: A total of 120 blood samples from 109 patients (including 10 patients suffered from more than one malaria episode, samples were collected during each episode) with P. vivax infection were genotyped. All samples were analysed by msp3a PCR-RFLP and msp1_b5 gene sequencing was performed on 57 samples. Genotyping protocol applied to distinguish between new infection or relapse from heterologus hypnozoites and treatment failure or relapse from homologus hypnozoites was based on analysing first msp3a by PCR-RFLP and secondly, only if the genotypes of the two samples are identical, on sequencing the msp1_b5 gene. RESULTS: msp3a alleles of three sizes were amplified by PCR: types A, B and C. Eleven different genotypes were identified among the 109 samples analysed by msp3a PCR-RFLP. In 13.8% of cases, a mixed genotype infection was observed. The sequence of msp1_b5 gene revealed 22 unique genotypes and 12.3% of cases with mixed infection. In the 57 samples analysed by both methods, 45 genotypes were found and 21% were mixed. Among ten patients with two or three malaria episodes, the protocol allowed to identify five new infections or relapses from heterologous hypnozoites and six treatment failures of relapses from homologous hypnozoites. CONCLUSION: The study showed a high diversity of msp3a and msp1_b5 genetic markers among P. vivax strains in French Guiana with a low polyclonal infection rate. These results indicated that the P. vivax genotyping protocol presented has a good discrimination power and can be used in clinical drug trials or epidemiological studies.
ISSN: 1475-2875

pasteur-00590981
https://hal-riip.archives-ouvertes.fr/pasteur-00590981
DOI : 10.1186/1475-2875-8-40
PUBMED : 19284592

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 Elsevier
Résumé : International audience
The objective of the study was to evaluate the distribution of methotrexate (MTX) in cerebrospinal fluid (CSF) lateral ventricles and in cisterna magna after 3rd intraventricular CSF administration in a rabbit model.MTX or gadolinium chelate (Gd-DOTA) was administered in the 3rd ventricle with a local microdialysis to study the pharmacokinetics at the site of administration and with a simultaneous magnetic resonance imaging (MRI) acquisition in the 3rd ventricle, the lateral ventricles and in the cisterna magna. A specific CSF Physiologically Based Pharmacokinetic (PBPK) model was then extrapolated for MTX from Gd-DOTA data.The relative contribution of elimination and distribution processes to the overall disposition of MTX and Gd-DOTA in the 3rd ventricle was similar (i.e., around 60% for CLE and 40% for CLI) suggesting that Gd-DOTA was a suitable surrogate marker for MTX disposition in ventricular CSF. The PBPK predictions for MTX both in CSF of the 3rd ventricle and in plasma were in accordance with the in vivo results.The present study showed that the combination of local CSF microdialysis with MRI acquisition of the brain ventricles and a PBPK model could be a useful methodology to estimate the drug diffusion within CSF ventricles after direct brain CSF administration. Such a methodology would be of interest to clinicians for a rationale determination and optimization of drug dosing parameters in the treatment of leptomeningeal metastases.
ISSN: 0939-6411

hal-01335562
https://hal.archives-ouvertes.fr/hal-01335562
https://hal.archives-ouvertes.fr/hal-01335562/document
https://hal.archives-ouvertes.fr/hal-01335562/file/PBPK%20model%20of%20methotrexate%20in%20cerebrospinal%20fluid.pdf
DOI : 10.1016/j.ejpb.2016.04.012

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Les leishmanioses sont des maladies parasitaires à transmission vectorielle observées sur tous les continents, à l’exception de l’Amérique du Nord et de l’Australie. Nous focaliserons ici sur la leishmaniose viscérale méditerranéenne due à Leishmania infantum et dont l’incidence annuelle est estimée entre 1200 et 2000 cas. Son cycle biologique est zoonotique avec un réservoir animal essentiellement canin. Les récentes observations épidémiologiques sont rapportées ici, notamment la mise en évidence du portage humain asymptomatique et l’extension de la zone endémique de la leishmaniose canine. La prise en charge thérapeutique de la leishmaniose viscérale méditerranéenne du patient immunocompétent fait essentiellement appel à l’amphotéricine B liposomale. Le débat existe toujours sur la pertinence d’une prophylaxie secondaire ou des traitements itératifs à chaque rechute chez le patient co-infecté par le VIH. Summary Leishmaniasis are protozoan infections transmitted by the bite of the sandflies, widely reported except in North-America and Australia. Here, we focus on mediterranean visceral leishmaniasis due to Leishmania infantum, with an estimated annual incidence of 1200–2000 cases. Its biological cycle is zoonotic and mainly involves the canine reservoir. The recent epidemiological observations are reported here, particularly the asymptomatic carriage but also the extension of the canine enzooty. Regarding treatment of immunocompetent patients, the drug of choice for mediterranean visceral leishmaniasis is liposomal amphotericin B. In case of HIV-Leishmania co-infection, the interest of secondary prophylaxis is still in debate
ISSN: 2210-6545

hal-01225489
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01225489
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01225489/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01225489/file/Mise%20au%20point%20et%20actualit%C3%A9s%20sur%20la%20leishmaniose%20visc%C3%A9rale%20m%C3%A9diterran%C3%A9enne.pdf
DOI : 10.1016/j.antinf.2014.12.005

Éditeur(s) : HAL CCSD
Résumé : Food-grade dairy propionibacteria are nutraceutical producers. They release short chain fatty acids (SCFAs), folic acid and cobalamin, which play a role in intestinal physiology. SCFAs induce apoptosis via the mitochondrial death pathway. We investigated the potential of dairy propionibacteria-fermented products to synergize with drugs used in gastric and colorectal cancer.Fermented milk contained high and viable populations of propionibacteria. This product, as well as its cell-free supernatant, were tested in vitro on gastric HGT-1 and colic HT-29 cells with respect to apoptosis and synergy with known anti-cancer molecules, camptothecin and the human cytokine TRAIL (TNF Related Apoptosis Inducing Ligand). Viability was monitored and apoptosis quantified by Hoescht staining, ROS production, mitochondrial membrane potential perturbation and caspases activity assay. A transcriptomic study on genome-wide microarray was performed in collaboration with the company Miltenyi.Fermented milk induced cell death in both gastric and colon cancer cells. Characterization of cells revealed cell cycle arrest, drop in intracellular ATP, depolarization of mitochondria, translocation of key apoptosis proteins, processing of caspases and fragmentation of the nucleus. Interestingly, the fermented milk was shown to potentiate the cytotoxic effect of molecules used in cancer chemotherapy, camptothecin and TRAIL. The observed synergistic pro-apoptotic effect between TRAIL and propionibacterial SCFAs depended on death receptors and on caspases, was more lethal on cancer cells than on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Transcriptomics revealed that propionibacterial metabolites boosted TRAIL-induced modulation of gene expression in human colon cancer cells.These results open new perspectives in the field of colon cancer cells prevention and/or treatment. The synergy with pro-apoptotic chemotherapy molecules suggests that such a fermented product, or the propionibacterium alone, may be proposed as a food supplement to enhance the effects of anticancer treatments.
The 2nd International conference on Cell Death In Cancer (CDIC)
La Baule, France

hal-01209622
https://hal.archives-ouvertes.fr/hal-01209622
PRODINRA : 261291

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Antisynthetase syndrome is an inflammatory myopathy frequently associated with pulmonary manifestations, especially interstitial lung diseases, and uncommonly pulmonary hypertension. In the context of a suggestive clinical and radiological picture, positive anti-RNA synthetase antibodies confirm the diagnosis. Anti-Jo1, anti-PL7, and anti-PL12 antibodies are the more commonly encountered. The presence of a number of extra-thoracic manifestations in association with pulmonary disease may suggest the diagnosis. These include: myalgia or muscular deficit, Raynaud's phenomenon, polyarthritis, fever, mechanics hands. Serum creatine kinase levels are usually increased. Electromyogram, muscular magnetic resonance imaging or muscle pathology are not mandatory to make the diagnosis. There is a high variability in symptoms and severity, between patients but also during the course of the disease in the same patient. The presence of an interstitial lung disease is a major prognostic factor and an indication for more intensive treatment, principally with systemic corticosteroids with or without immunosuppressive drugs. Improving respiratory physicians’ knowledge of this disease, which is often revealed by its pulmonary manifestations, should help diagnosis, therapeutic management, and possibly prognosis.
Le syndrome des antisynthétases correspond à une myopathie inflammatoire fréquemment associée à une atteinte pulmonaire, surtout parenchymateuse (pneumopathie infiltrante diffuse) et plus rarement vasculaire (hypertension pulmonaire). Devant un tableau clinique et radiologique évocateur, la présence d’anticorps anti-ARNt synthétases signe le diagnostic. Les plus fréquents de ces auto-anticorps sont les anti-Jo1, les anti-PL7 et les anti-PL12. De nombreuses manifestations cliniques extrathoraciques associées à l’atteinte pulmonaire peuvent orienter le diagnostic : myalgies ou déficit musculaire, phénomène de Raynaud, polyarthrite, fièvre et « mains de mécaniciens ». Une augmentation des créatine-phospho-kinases est quasi constante. Le recours à l’électromyogramme, à l’imagerie musculaire par résonance magnétique ou à l’histologie n’est pas systématique. Néanmoins, il existe une grande variabilité des symptômes et de leur sévérité d’un patient à l’autre ou au long de l’évolution de la maladie. L’atteinte pulmonaire est un facteur pronostic majeur et incite à traiter de manière intensive les patients, principalement par corticothérapie systémique, voire d’emblée par association corticoïdes et immunosuppresseurs. Mieux connaître cette pathologie qui est souvent de révélation pneumologique permettrait d’améliorer le diagnostic et la prise en charge thérapeutique, voire même le pronostic.
ISSN: 0761-8425

hal-01085369
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085369
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085369/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085369/file/Manifestations%20pulmonaires%20du%20syndrome%20des%20antisynth%C3%A9tases_accepted.pdf
DOI : 10.1016/j.rmr.2014.07.013

Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Sickle cell disease is characterized by painful vaso-occlusive crises during which abnormal interactions between erythroid adhesion molecules and vessel-wall proteins are thought to play a critical role. Hydroxyurea, the only drug with proven benefit in sickle cell disease, diminishes these interactions, but its mechanism of action is not fully understood. We report that, under hydroxyurea, expression of the unique erythroid laminin receptor Lu/BCAM was increased, but red blood cell adhesion to laminin decreased. Because Lu/BCAM phosphorylation is known to activate cell adhesion to laminin, it was evaluated and found to be dramatically lower in hydroxyurea-treated patients. Analysis of the protein kinase A pathway showed decreased intracellular levels of the upstream effector cyclic adenosine monophosphate during hydroxyurea treatment. Using a cellular model expressing recombinant Lu/BCAM, we showed that hydroxyurea led to decreased intracellular cyclic adenosine monophosphate levels and diminished Lu/BCAM phosphorylation and cell adhesion. We provide evidence that hydroxyurea could reduce abnormal sickle red blood cell adhesion to the vascular wall by regulating the activation state of adhesion molecules independently of their expression level.
ISSN: 0006-4971

inserm-00821117
http://www.hal.inserm.fr/inserm-00821117
http://www.hal.inserm.fr/inserm-00821117/document
http://www.hal.inserm.fr/inserm-00821117/file/Bartolucci_Blood_2010.pdf
DOI : 10.1182/blood-2009-12-257444