Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease

The severity of cystic fibrosis (CF) pulmonary disease is not directly related to CFTR genotype but depends upon several parameters, including neutrophil-dominated inflammation. Identification of agents modulating inflammation constitutes a relevant goal. Myeloperoxidase (MPO) is involved in both microbicidal and proinflammatory neutrophil activities. The aim of this study was to evaluate whether the −463GA MPO promoter polymorphism is linked to clinical severity of CF-associated pulmonary inflammation. This polymorphism significantly affects the level of MPO gene expression in leukocytes and the G allele is more expressing than the A allele. We show that MPO genotype significantly influences the severity of pulmonary disease in early stages, prior to the development of chronic lung infections, with GG genotype being associated with more severe CF disease. Our findings indicate that the level of MPO gene expression influences the CF pathogenesis, presumably reflecting cellular damage by MPO-generated oxidants or other activity of MPO in airway inflammation

Toll-like receptor 4 selective inhibition in medullar microenvironment alters multiple myeloma cell growth.

peer reviewedBone marrow (BM) mesenchymal stromal cells (MSCs) are abnormal in multiple myeloma (MM) and play a critical role by promoting growth, survival, and drug resistance of MM cells. We observed higher Toll-like receptor 4 (TLR4) gene expression in MM MSCs than in MSCs from healthy donors. At the clinical level, we highlighted that TLR4 expression in MM MSCs evolves in parallel with the disease stage. Thus, we reasoned that the TLR4 axis is pivotal in MM by increasing the protumor activity of MSCs. Challenging primary MSCs with TLR4 agonists increased the expression of CD54 and interleukin-6 (IL-6), 2 factors directly implicated in MM MSC-MM cell crosstalk. Then, we evaluated the therapeutic efficacy of a TLR4 antagonist combined or not with conventional treatment in vitro with MSC-MM cell coculture and in vivo with the Vk*MYC mouse model. Selective inhibition of TLR4 specifically reduced the MM MSC ability to support the growth of MM cells in an IL-6-dependent manner and delayed the development of MM in the Vk*MYC mouse model by altering the early disease phase in vivo. For the first time, we demonstrate that specific targeting of the pathological BM microenvironment via TLR4 signaling could be an innovative approach to alter MM pathology development

De nouveaux usages pour les zones humides du Sud-Ouest (France) : entre conservatoire de biodiversité, éducation à l'environnement et valorisation multipatrimoniale

International audienc

De la naturalité des zones humides. Origine, artificialisation, restauration des zones humides du Sud-Ouest (France)

International audienc

Improvement of the hydroxyapatite mechanical properties by direct microwave sintering in single mode cavity

International audienceThe main purpose of this study consists in investigating the direct microwave sintering of hydroxyapatite (HA) in a single mode cavity. Firstly, stoichiometric HA powders were synthesized by a coprecipitation method from diammonium phosphate and calcium nitrate solutions and shaped by slip-casting. Then, using the one-step microwave process, dense pellets with fine microstructures were successfully obtained in short sintering timespan. A parametric study permitted to determine the influence of powder grain size, sintering temperature and dwell time on the sintered samples microstructures. The Young's modulus (E) and hardness (H) were measured by nanoindentation and the values discussed according to the microstructure. Finally, the resulting mechanical properties determined on the microwave sintered samples (E = 148.5 GPa, H = 9.6 GPa, σcompression = 531.3 MPa and KIC = 1.12 MPa m1/2) are significantly higher than those usually reported in the literature, whatever the sintering process, and could allow the use of HA for structural applications

L’Église : institution et foi

Le discrédit jeté sur les institutions devient aujourd’hui une nouvelle idéologie qui oublie de se soumettre elle-même à la critique. C’est le cas aussi pour l'institution ecclésiale, qui est durement contestée par beaucoup de ses membres. Ne convient-il pas, sans rien oublier, bien au contraire, des acquis récents de l’ecclésiologie et de la pratique ecclésiale, de repenser le fondement théologique de l’Église comme institution? Un historien, un évêque, un sociologue, un exégète, un ecclésiologue, un théologien tentent d’éclairer, chacun de leur point de vue, ce problème difficile mais essentiel pour l'Église d’aujourd'hui. Ce volume résulte d’une session théologique, tenue en 1978 à l'École des sciences philosophiques et religieuses des Facultés universitaires Saint-Louis

Efficacy of Zidovudine Compared to Stavudine, Both in Combination with Lamivudine and Indinavir, in Human Immunodeficiency Virus-Infected Nucleoside-Experienced Patients with No Prior Exposure to Lamivudine, Stavudine, or Protease Inhibitors (Novavir Trial)

We compared the efficacy and the toxicity of zidovudine (AZT) versus stavudine (d4T), in combination with lamivudine (3TC) and indinavir, in AZT-, dideoxyinosine (ddI)-, and/or dideoxycytosine (ddC)-experienced patients in a randomized comparative multicenter trial. One hundred seventy human immunodeficiency virus type 1 (HIV-1)-infected patients, who had received AZT, ddI, and/or ddC for at least 6 months but were naive for d4T, 3TC, and protease inhibitors, were randomized to AZT at 250 to 300 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h or to d4T at 40 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h. The primary endpoint was time to virological failure, defined as plasma HIV-1 RNA levels of >5,000 copies/ml after at least 8 weeks of antiretroviral therapy. Additional endpoints were change from baseline in CD4 cell counts, AIDS-defining events and adverse events, and proportion of patients with HIV-1 RNA levels of <500 copies/ml and HIV-1 RNA levels of <50 copies/ml. At week 80, 15 patients in the AZT arm and 14 patients in the d4T arm had reached the primary endpoint, and time to virological failure did not differ between the two arms (P = 0.98). In the d4T and in the AZT arms, 67 and 73% of patients, respectively, had HIV-1 RNA levels of <500 copies/ml (P = 0.50). The median change from baseline in CD4 cell count was 195 × 10(6) and 175 × 10(6)/liter for the d4T- and AZT-containing arms, respectively. The proportions of patients with HIV-1 RNA levels of <50 copies/ml at weeks 8, 16, and 24 were similar in the two arms. The occurrence of serious adverse events was not significantly different between arms. In conclusion, in these patients heavily pretreated with AZT, switching from AZT to d4T when initiating indinavir and 3TC did not bring any additional benefit compared to maintaining AZT

Functional Comparison between Healthy and Multiple Myeloma Adipose Stromal Cells

Multiple myeloma (MM) is an incurable B cell neoplasia characterized by the accumulation of tumor plasma cells within the bone marrow (BM). As a consequence, bone osteolytic lesions develop in 80% of patients and remain even after complete disease remission. We and others had demonstrated that BM-derived mesenchymal stromal cells (MSCs) are abnormal in MM and thus cannot be used for autologous treatment to repair bone damage. Adipose stromal cells (ASCs) represent an interesting alternative to MSCs for cellular therapy. Thus, in this study, we wondered whether they could be a good candidate in repairing MM bone lesions. For the first time, we present a transcriptomic, phenotypic, and functional comparison of ASCs from MM patients and healthy donors (HDs) relying on their autologous MSC counterparts. In contrast to MM MSCs, MM ASCs did not exhibit major abnormalities. However, the changes observed in MM ASCs and the supportive property of ASCs on MM cells question their putative and safety uses at an autologous or allogenic level