Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6

SummaryQuantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (i.v.) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 × 106 hMSCs were i.v. infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr, but <1000 cells appeared in six other tissues. The hMSCs in lung upregulated expression of multiple genes, with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, i.v. hMSCs, but not hMSCs transduced with TSG-6 siRNA, decreased inflammatory responses, reduced infarct size, and improved cardiac function. I.v. administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest that improvements in animal models and patients after i.v. infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6

Evaluación de cobre y cinc en suero sanguíneo de pacientes diabéticos con y sin pie diabético

Los micronutrientes, cobre (Cu) y cinc (Zn) cumplen funciones indispensables para el desarrollo y crecimiento celular. Por tal razón, este trabajo presenta la evaluación de los niveles séricos de Cu y Zn de pacientes diabéticos con y sin pie diabético (DPD y DSPD) con edades comprendidas entre 55 y 75 años, empleando la espectrometría de absorción atómica con llama. Las muestras, una vez extraídas, se trasvasaron a tubos de polipropileno sin anticoagulante, se separaron por centrifugación para la obtención del suero y se almacenaron a 4 °C hasta su análisis. Para la determinación espectrométrica de Cu y Zn, las muestras se diluyeron con agua desionizada (2x). Las concentraciones medias de Cu y Zn para los DPD fueron de 1,017 y 1,134 mg/L para Cu; y de 1,009 y 0,907 mg/L para Zn, mientras que en DSPD fueron de 1,094 y 0,970 mg/L para Cu; y de 0,661 y 0,807 mg/L para Zn, en mujeres y hombres, respectivamente, sin que existieran diferencias (p&gt;0,05) en las concentraciones de Cu y Zn entre los DPD y DSPD, encontrándose diferencias significativas (p≤0,05) en las concentraciones de Zn en mujeres DSPD. En consecuencia, se puede concluir que los niveles de Cu y Zn están en concentraciones adecuadas para ambos grupos, lo que permite inferir que el metabolismo de estos oligoelementos se encuentra en equilibrio en los pacientes DPD y DSPD, debido a la adecuada ingesta de dichos minerales diariamente. &nbsp; Palabras clave: Espectrometría de absorción atómica con llama, Cu, Zn, pie diabético, diabetes mellitus. &nbsp; Abstract Copper and zinc micronutrients fulfill essential functions for cell growth and development. For this reason, this paper presents the evaluation of serum levels of Cu and Zn of diabetic patients with and without diabetic foot (DPD and DSPD) aged between 55 and 75 years, using flame atomic absorption spectrometry. Once the samples were extracted, were transferred to polypropylene tubes without anticoagulant, which were separated by centrifugation to obtain the serum, and stored at 4°C until their analysis. For the spectrometric determination of Cu and Zn the samples were diluted with deionized water (2x). The mean concentrations of Cu and Zn for the DPD groups was 1.017mg/L; 1,134mg/L for copper; and 1.009mg/L; 0.907mg/L for Zn and the DSPD group was 1.094mg/L; 0.970mg/L for copper; and 0.661mg/L; 0.807mg/L for Zn, in women and men respectively, so there is no significant difference (p&gt;0.05) in the Cu and Zn concentrations at DPD and DSPD, finding significant differences (p≤0.05) in Zn´s concentrations in women DSPD. Consequently, it can be concluded that Cu and Zn levels are in adequate concentrations for both groups. This allows to infer that metabolism of these trace elements is in equilibrium in the DPD and DSPD patients, due to the adequate intake of these minerals daily. &nbsp; Keywords: Atomic absorption spectrometry flame, copper, zinc, diabetic foot, diabetes mellitus

Angiotensin II Infusion Induces Marked Diaphragmatic Skeletal Muscle Atrophy

Advanced congestive heart failure (CHF) and chronic kidney disease (CKD) are characterized by increased angiotensin II (Ang II) levels and are often accompanied by significant skeletal muscle wasting that negatively impacts mortality and morbidity. Both CHF and CKD patients have respiratory muscle dysfunction, however the potential effects of Ang II on respiratory muscles are unknown. We investigated the effects of Ang II on diaphragm muscle in FVB mice. Ang II induced significant diaphragm muscle wasting (18.7±1.6% decrease in weight at one week) and reduction in fiber cross-sectional area. Expression of the E3 ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1) and of the pro-apoptotic factor BAX was increased after 24 h of Ang II infusion (4.4±0.3 fold, 3.1±0.5 fold and 1.6±0.2 fold, respectively, compared to sham infused control) suggesting increased muscle protein degradation and apoptosis. In Ang II infused animals, there was significant regeneration of injured diaphragm muscles at 7 days as indicated by an increase in the number of myofibers with centralized nuclei and high expression of embryonic myosin heavy chain (E-MyHC, 11.2±3.3 fold increase) and of the satellite cell marker M-cadherin (59.2±22.2% increase). Furthermore, there was an increase in expression of insulin-like growth factor-1 (IGF-1, 1.8±0.3 fold increase) in Ang II infused diaphragm, suggesting the involvement of IGF-1 in diaphragm muscle regeneration. Bone-marrow transplantation experiments indicated that although there was recruitment of bone-marrow derived cells to the injured diaphragm in Ang II infused mice (267.0±74.6% increase), those cells did not express markers of muscle stem cells or regenerating myofibers. In conclusion, Ang II causes marked diaphragm muscle wasting, which may be important for the pathophysiology of respiratory muscle dysfunction and cachexia in conditions such as CHF and CKD

Editorial

Semprun Jorge. Editorial. In: Matériaux pour l'histoire de notre temps, n°3-4, 1985. L'Espagne, 1900-1985, sous la direction de Stéphane Courtois. pp. 3-4

Editorial

Semprun Jorge. Editorial. In: Matériaux pour l'histoire de notre temps, n°3-4, 1985. L'Espagne, 1900-1985, sous la direction de Stéphane Courtois. pp. 3-4

Éditorial

International audienc

Économie politique et philosophie dans les « Grundrisse » de Marx

Semprun Jorge. Économie politique et philosophie dans les « Grundrisse » de Marx. In: L'Homme et la société, N. 7, 1968. numéro spécial 150° anniversaire de la mort de Karl Marx. pp. 57-68

Le point de vue d'Orwell

Semprun Jorge. Le point de vue d'Orwell. In: Matériaux pour l'histoire de notre temps, n°5, 1986. L'Espagne vers l'Europe, sous la direction de Stéphane Courtois . pp. 32-36