Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Myelin Regeneration in an Animal Model of Multiple Sclerosis.

Mesenchymal stem/stromal cells (MSCs) display potent immunomodulatory and regenerative capabilities through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EVs). These functional properties of MSCs make them ideal candidates for the treatment of degenerative and inflammatory diseases, including multiple sclerosis (MS). MS is a heterogenous disease that is typically characterized by inflammation, demyelination, gliosis and axonal loss. In the current study, an induced experimental autoimmune encephalomyelitis (EAE) murine model of MS was utilized. At peak disease onset, animals were treated with saline, placenta-derived MSCs (PMSCs), as well as low and high doses of PMSC-EVs. Animals treated with PMSCs and high-dose PMSC-EVs displayed improved motor function outcomes as compared to animals treated with saline. Symptom improvement by PMSCs and PMSC-EVs led to reduced DNA damage in oligodendroglia populations and increased myelination within the spinal cord of treated mice. In vitro data demonstrate that PMSC-EVs promote myelin regeneration by inducing endogenous oligodendrocyte precursor cells to differentiate into mature myelinating oligodendrocytes. These findings support that PMSCs' mechanism of action is mediated by the secretion of EVs. Therefore, PMSC-derived EVs are a feasible alternative to cellular based therapies for MS, as demonstrated in an animal model of the disease

Nutrition in hemodialysis patients previously on a supplemented very low protein diet

Nutrition in hemodialysis patients previously on a supplemented very low protein diet.BackgroundNutritional safety of protein-restricted diets in patients with chronic renal failure is controversial. In the present study, we have assessed the evolution of nutritional status after initiation of hemodialysis in patients previously treated by a supplemented very low protein diet (SVLPD).MethodsNutritional data were prospectively collected during the first year of hemodialysis from 15 consecutive patients treated with a SVLPD (0.3 g protein/kg/day supplemented with essential amino acids, calcium, iron, and vitamins) and compared to 15 age- and gender-matched end-stage renal disease (ESRD) patients previously on a less-restricted diet (0.90 ± 0.21 g protein/kg/day) who started hemodialysis during the same period. Dual-energy x-ray absorptiometry (DEXA) was used to assess body composition at 0, 6, and 12 months. Hemodialysis prescriptions, biologic data and 3-day food records were collected every 3 months.ResultsProtein intake was higher than 1.2 g/kg/day in both groups as soon as 3 months after the start of hemodialysis. Albumin and prealbumin increased significantly during the first 6 months in all patients. Body mass index (BMI) increased in all patients (+0.97 ± 1.31 kg/m2; P < 0.001) reflecting a gain in fat mass in the overall population (+2.36 ± 2.94 kg/m2; P < 0.001) while lean body mass remained stable overall.ConclusionOnce on hemodialysis, SVLPD patients rapidly increased protein intake. Nutritional status improved in all patients, with a gain in fat mass in all, and a gain in lean body mass in SVLPD men only. These data indicate that treatment with a SVLPD prior to hemodialysis initiation is nutritionally safe

EJNMMI Res

Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [C]-PBR28 and [F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [C]-PBR28. All in vitro sections showed specific binding of [F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [C]-PBR28 or [F]-PBR06 was negative in all participants. Despite good uptake on surgical samples in vitro, [C]-PBR28 and [F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease. NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov

Large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>Renal hypertrophy occurs early in diabetic nephropathy, its later value is unknown. Do large kidneys still predict poor outcome in patients with diabetes and Chronic Kidney Disease (CKD)?</p> <p>Methods</p> <p>Seventy-five patients with diabetes and CKD according to a Glomerular Filtration Rate (GFR, by 51Cr-EDTA clearance) below 60 mL/min/1.73 m²or an Albumin Excretion Rate above 30 mg/24 H, had an ultrasound imaging of the kidneys and were cooperatively followed during five years by the Diabetology and Nephrology departments of the Centre Hospitalier Universitaire de Bordeaux.</p> <p>Results</p> <p>The patients were mainly men (44/75), aged 62 ± 13 yrs, with long-standing diabetes (duration:17 ± 9 yrs, 55/75 type 2), and CKD: initial GFR: 56.5 (8.5-209) mL/min/1.73 m², AER: 196 (20-2358) mg/24 H. Their mean kidney lenght (108 ± 13 mm, 67-147) was correlated to the GFR (r = 0.23, p < 0.05). During the follow-up, 9/11 of the patients who had to start dialysis came from the half with the largest kidneys (LogRank: p < 0.05), despite a 40% higher initial isotopic GFR. Serum creatinine were initially lower (Small kidneys: 125 (79-320) μmol/L, Large: 103 (50-371), p < 0.05), but significantly increased in the "large kidneys" group at the end of the follow-up (Small kidneys: 129 (69-283) μmol/L, Large: 140 (50-952), p < 0.005 vs initial). The difference persisted in the patients with severe renal failure (KDOQI stages 4,5).</p> <p>Conclusions</p> <p>Large kidneys still predict progression in advanced CKD complicating diabetes. In these patients, ultrasound imaging not only excludes obstructive renal disease, but also provides information on the progression of the renal disease.</p

The Promise : Can it be done (with) in Business ?

International audienc

Introduction

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La promesse a-t-elle sa place dans les affaires ?

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Autoradiographie quantitative à l'aide des nouveaux systèmes d'imagerie Beta à haute résolution (applications à l'évaluation de médicaments ou à la mise au point de radiopharmaceutiques)

L'autoradiographie, technique d'imagerie qui permet d'obtenir la répartition spatiale d'un isotope radioactif au sein d'un tissu, est généralement réalisée à l'aide de films ou d'émulsions photographiques. Cette méthodologie est difficile à mettre en oeuvre et ne permet pas une quantification précise de la radioactivité in situ. Nous avons contribué au développement de nouveaux détecteurs d'imagerie beta haute résolution destinés à supplanter les films avec un comptage direct de la radioactivité beta, tout en gardant, voire améliorant, les performances par rapport à ces derniers. En particulier la sensibilité de détection est considérablement accrue, multipliant par un facteur 100 à 500 la rapidité d'obtention des images. La linéarité de réponse des détecteurs est améliorée permettant une augmentation de la dynamique de comptage par rapport aux émulsions photographiques. La quantification de la radioactivité au sein des tissus est alors obtenue de façon simple et fiable. L'imagerie multi-isotopes est rendue possible grâce à des algorithmes de séparation utilisant les différences d'énergies ou de périodes de décroissance radioactive des isotopes. Les applications potentielles sont nombreuses dans le domaine des études de médicaments ou la mise au point de radiopharmaceutiques.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF