Lifestyle Behaviours and Plasma Vitamin C and β-Carotene Levels from the ELAN Population (Liège, Belgium)

Several factors, including fruit and vegetables intakes, have been shown to significantly influence the plasma concentrations of the two antioxidants vitamin C and β-carotene. Deficiency levels of 6 mg/L (34.2 μM) for vitamin C and of 0.22 mg/L (0.4 μM) for β-carotene have been suggested below which cardiovascular risk might be increased. The present study performed on 897 presumably healthy subjects aged 40–60 years aimed to examine how modifiable lifestyle factors may be related to vitamin C and/or β-carotene deficiency. Gender, smoking, lack of regular physical activity and of daily fruit consumption (≥2/day), and social status (in particular, unemployment) were found to be significant risk factors for vitamin C deficiency. For β-carotene deficiency, the same factors were identified except social status; moreover, overweight and OC use in women were also found to have a deleterious effect. For non exposed subjects, the probability of developing vitamin C deficiency was 4% in men and 2.4% in women. This probability increased to 66.3% for men and to 44.3% for women (and even to 50.4% under OC use), when all risk factors were present. For β-carotene deficiency, the corresponding probabilities were equal to 29.7% in men and 13.7% in women (no risk factor present), and to 86.1% for men and 69.9% (91.6% for OC use) for women (all factors present), respectively

Effectiveness of a real-life program (DIAfit) to promote physical activity in patients with type 2 diabetes: a pragmatic cluster randomized clinical trial.

INTRODUCTION The aim of this study was to evaluate the effectiveness of a real-life clinical physical activity program (DIAfit) on improving physical fitness, body composition, and cardiometabolic health in an unselected population with type 2 diabetes mellitus, and to compare the effects of two variants a different exercise frequencies on the same outcomes. RESEARCH DESIGN AND METHODS This was a cluster randomized-controlled assessor-blind trial conducted in 11 clinical centres in Switzerland. All participants in the clinical program with type 2 diabetes were eligible and were randomized to either standard (3 sessions/week for 12 weeks) or alternative (1 session/week for the first four weeks, then 2 sessions/week for the rest of 16 weeks) physical activity program each consisting of 36 sessions of combined aerobic and resistance exercise. Allocation was concealed by a central office unrelated to the study. The primary outcome was aerobic fitness. Secondary outcome measures included: body composition, BMI, HbA1c, muscle strength, walking speed, balance, flexibility, blood pressure, lipid profile. RESULTS All 185 patients with type 2 diabetes (mean age 59.7 +-10.2 years, 48% women) agreed to participate and were randomized in two groups: a standard group (n=88) and an alternative group (n=97)). There was an 11% increase in aerobic fitness after the program (12.5 Watts; 95% CI 6.76 to 18.25; p<0.001). Significant improvements in physical fitness, body composition, and cardiometabolic parameters were observed at the end of the DIAfit program (improvements between 2-29%) except for lean body mass, triglycerides and cholesterol. No differences were observed between both programs, except for a larger weight reduction of -0.97kg (95% CI -0.04 to -1.91; p=0.04) in the standard program. CONCLUSIONS Both frequency variants of the nation-wide DIAfit program had beneficial effects on physical fitness, HbA1c, body composition, and blood pressure in type 2 diabetes patients and differences were negligible. CLINICAL TRIAL REGISTRATION clinicaltrials.gov, identifier NCT01289587

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Cell cycle activation of hematopoietic progenitor cells increases very late antigen-5-mediated adhesion to fibronectin.

peer reviewedRecent studies suggested that trafficking of hematopoietic progenitor cells is related to cell cycle status. We studied whether adhesion of progenitor cells to extracellular matrix proteins was modulated by cell cycle transit.Mobilized peripheral blood CD34+ cells were stimulated ex vivo for 48 hours with stem cell factor, flt-3 ligand, and thrombopoietin and fractionated by adhesion to fibronectin or vascular cell adhesion molecule-1 (VCAM-1). Adherent and nonadherent cells were assayed for cell cycle status, long-term culture-initiating cell frequency, and integrin function. Binding to fibronectin, but not to VCAM-1, displayed a cell cycle selectivity as the adherent fraction to fibronectin was enriched in cycling CD34+ cells and in cycling long-term culture-initiating cells compared to the nonadherent fraction. Combined cell cycle and phenotypic analysis showed that the expression of VLA-5 was upregulated during S/G2+M but that of VLA-4 remained constant. The selective binding of cycling CD34+ cells to fibronectin was reverted by anti-VLA-5 but not by anti-VLA-4 blocking antibodies. Also, cycling CD34+ cells preferentially adhered to the VLA-5 binding domain but not to the VLA-4 binding domain of fibronectin. Adhesion of cycling CD34+ cells to fibronectin was a reversible process modulated by cell cycle progression, because adherent cells could exit the cell cycle and return to a nonadhesive state within an additional 48-hour culture period.The results indicate that the enhanced binding capacity of cycling progenitor cells to fibronectin is mediated by VLA-5

Clinical - scale expansion of mesenchymal stromal cells: a large banking experience

Background: Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn’s disease, solid organ transplantation). As the percentage of MSC precursors in bone marrow is very low, these must be expanded in vitro to obtain therapeutic cell doses. We describe here the constitution of an allogeneic human third-party MSC bank from screened healthy volunteer donors in compliance with quality specifications and ISCT-release criteria and report follow-up of different aspects of this activity since 2007. Methods: 68 clinical-grade large-scale MSC cultures were completed and analyzed. The whole process was described, including volunteer donor screening, bone marrow collection, mononuclear cell isolation and expansion over 4 weeks, harvesting, cryopreservation, release, administration and quality controls of the cells (including microbiology, phenotype, and potency assays). Results: From 59 validated donors, 68 cultures were completed (mean of final yields: 886 × 106 cells/culture) and a total of 464 MSC aliquots have been produced and stored in liquid nitrogen (mean of 132.8 × 106 cells/bag). Each MSC batch underwent extensive testing to verify its conformity with EBMT and ISCT release criteria and was individually validated. As of June 1 2015, 314 bags have been released and infused to patients included in 6 different clinical protocols. All thawed MSC units satisfied to release criteria and no infusion-related toxicity was reported. Conclusion: In conclusion, despite low passage cultures, we have been able to create an allogeneic “off-the-shelf” MSC bank with a large number of frozen aliquots and report here an efficient clinical-grade MSC banking activity in place for more than 7 years. Our challenge now is to produce MSC in compliance with good manufacturing practices (GMP) as, in the meantime, MSC have become considered as advanced therapy medicinal products (ATMP). Another significant challenge remains the development of relevant potency assay

Urgences pédiatriques chirurgicales de Hautepierre (état des lieux et rôle du médecin généraliste)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

The use of mesenchymal stromal cells in solid organ transplantation

peer reviewedOrgan transplantation is the only definitive treatment for many critical diseases of the liver, kidney, heart, pancreas, and lungs. Although it is the primary therapeutic option at present, transplanted patients have to deal with the numerous side effects of life-long dependence on immunosuppressive drugs, and these drugs still fail to prevent chronic rejection of the transplanted organ in many cases. The risk of developing cancer and opportunistic infections is also markedly increased in solid organ transplant (SOT) recipients receiving long-term immunosuppressive therapy. Cancer and opportunistic infections cannot be completely avoided since they result from the immunosuppressive drugs used posttransplant that affect not only the anti-graft response but also the entire immune response. Finding a way to establish donor-specific immunological tolerance without the need for nonspecific immunosuppression remains one of the major goals in transplantation medicine [1,2]. Another important aim is the improvement of graft survival and function. Overall, graft survival is about 15 years, but the increasing shortage of organs has led to the use of expanded criteria for donor organs often donated by older individuals, which are less robust organs than those donated by younger donors. Mesenchymal stromal cell (MSCs) are currently being evaluated in SOT with the hope of achieving more selective immunosuppression, better graft function, and longer graft survival

Modulation par le cycle cellulaire de l'implantation des cellules souches hématopoïétiques

peer reviewe

A picture on the IFR140 microscopy facility

PosterThe ever growing needs to visualize and characterize biological systems leads to a constant increasing demand in imaging techniques. In order to offer to the scientific community an up to date technology and keeping in mind the high cost levels of those equipments, a common microscopy facility has been set up in Rennes, within a federative structure called IFR 140. The facility offers a large panel of widefield fluorescence as well as confocal imaging systems and a micro-injection system. (http://microscopie.univ-rennes1.fr/) Two engineers are in charge of the equipment, technological developments and survey; moreover they organize training sessions towards demanding scientists and finally offer advice for experimental design and result analysis. Two scientists assume the interaction with the scientific community and propose strategic developments so as to constantly improve the facility's performance. In the context of the 11th scientific meeting of “Réseau LARC-Neurosciences” we take the opportunity to present you our facility and to favour interplay with scientists for whom microscopy is an invaluable tool