Aldosterone/Mineralocorticoid Receptor Downstream Targets as Novel Therapeutic Targets to Prevent Cardiovascular Remodeling

The incidence of heart failure (HF) is increasing because of aging of the population. Despite optimal therapy, patients with HF experience disease progression associated with high mortality rates. HF is still the first cause of hospital admission in subjects aged >65 years. The obvious solution for HF epidemics is to prevent new-onset HF with therapies directed specifically to mechanistic targets that are involved in the transition to HF. The mineralocorticoid receptor (MR) and its natural ligand, the hormone aldosterone (Aldo), play important roles during cardiac and arterial remodeling, but the underlying effects are still not understood. MR antagonists are highly recommended for treatment of systolic symptomatic HF. However, adverse effects limit their use in clinical practice. Galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), and cardiotrophin-1 (CT-1) have been identified as highly focused targets controlling downstream key MR-mediated HF mechanisms. Therefore, interfering with mechanistic pathways involved in downstream MR activation may provide therapeutic alternatives to MR antagonists. The aim of this review is to focus on the role of the MR biotargets in cardiovascular remodeling

Impacto Femoroacetabular

Femoroacetabular impingement (FAI) is a clinical-radiological syndrome in which the anatomic abnormalities in the transition space between the femoral head and the anterior acetabular rim, results in abnormal contact between them. It must be considered in the differential diagnosis of hip pain, especially among young people. An early diagnosis and a proper and timely treatment allow patients to return to work and sports activities. So far, little is known about FAI among medical specialties, so the purpose of this review is to provide information related to the diagnosis, treatment and prognosis of this pathology.El choque femoroacetabular (CFA), también conocido como atrapamiento femoroacetabular, o impingement femoroacetabular es un síndrome clínico-radiológico que se caracteriza por presentar un conflicto de espacio en la transición entre la cabeza y el cuello femoral, con el reborde acetabular anterior. Es una causa a tener en cuenta en el diagnóstico diferencial de la coxalgia, especialmente en la población joven y laboralmente activa. Esto resalta la importancia sobre el conocimiento de esta patología, ya que su diagnóstico temprano permitirá la realización de un tratamiento correcto y oportuno, permitiendo de esta forma el regreso a las actividades laborales y deportivas de los pacientes. Hasta el momento es una entidad poco conocida entre las diferentes especialidades médicas, por lo que el objetivo de la presente revisión es aportar datos relacionados al diagnóstico, tratamiento y pronóstico de esta patología

Developing of control decision algorithms for its application in portable climate chambers

[Resumen] El control de mercancías perecederas es uno de los temas de interés prioritario en la gestión sostenible de los productos. El desarrollo de sistemas portables fácilmente reproducibles supondría la posibilidad de ensayar los efectos de perturbaciones térmicas en las mercancías perecederas para predecir su vida útil. El objetivo del proyecto consiste en diseñar y mejorar la gestión de la temperatura y humedad en habitáculos aislados térmicamente para el control preciso de los parámetros en el estudio de la vida útil de productos perecederos. Para ello, se realizará un estudio con un simulador en el que se controlarán las condiciones de calidad de determinados productos perecederos, alterando las condiciones de conservación dentro de la cámara mediante la introducción de ciclos de temperatura reales en el transporte de mercancías. La finalidad principal de este trabajo se basa en que el simulador sea totalmente reproducible y alcanzable para cualquier tipo de usuario final. Para ello, se implementará una arquitectura de adquisición de datos a tiempo real en código abierto mediante soluciones abiertas, flexibles y económicas proporcionadas por la plataforma Raspberry Pi.[Abstract] The monitoring of perishable goods is one of the priority areas of interest in sustainable product management. The development of easily reproducible portable systems would make it possible to test the effects of thermal disturbances on perishable goods in order to predict their shelf life. The aim of the project is to design and improve the management of temperature and humidity in thermally insulated enclosures for the precise control of parameters in the study of the shelf life of perishable products. To this end, a study will be carried out with a simulator in which the quality conditions of certain perishable products will be controlled, altering the conservation conditions inside the chamber by introducing real temperature cycles in the transport of goods. The main purpose of this work is based on making the simulator fully reproducible and achievable for any type of end user. To this end, an open source real-time data acquisition architecture will be implemented using open, flexible and cost-effective solutions provided by the Raspberry Pi platform

Design of a controlled climatic chamber to reproduce the transportation of perishable commodities

[Resumen] La necesidad de analizar la pérdida de calidad en los alimentos se ha ido incrementando en los últimos tiempos de manera progresiva, debido a las cada vez más restrictivas condiciones de trazabilidad en las diferentes fases de distribución de los productos perecederos. Disponer de herramientas que permitan estimar las pérdidas de calidad en estas fases logísticas, ayudaría a reducir el desperdicio de alimentos desechados muchas veces por inadecuadas condiciones de conservación. El objetivo del proyecto, donde se encuadra este trabajo, consiste en la obtención de indicadores de pérdidas de calidad de productos cuando están sometidos a variaciones térmicas no deseadas. Estos indicadores, proporcionarían valores cualitativos de la calidad de la mercancía estimando variaciones de la vida comercial del producto o “shelf life”. Como parte de este proyecto, en este trabajo se ha diseñado y construido una cámara climática portátil en la que se pueden reproducir ciclos térmicos controlados durante la vida útil del producto y, de ese modo, evaluar distintos parámetros de calidad y relacionarlos con las condiciones de conservación. Debido al alto número de ensayos que es necesario realizar para obtener indicadores fiables, este trabajo propone el diseño de una cámara de bajo coste fácilmente reproducible y escalable donde sea factible someter al producto perecedero a alteraciones térmicas controladas durante la vida comercial del producto, y obtener un shelf-life dinámico en función de las variaciones de las condiciones climáticas. Este trabajo aborda el diseño, dimensionamiento, la instrumentación y los diferentes elementos que componen el sistema de control, además de la identificación y el ajuste del regulador. Los resultados y conclusiones permiten validar el diseño planteado quedando, la cámara desarrollada, como una herramienta útil para obtener indicadores de pérdidas de calidad ante diferentes condiciones climáticas.[Abstract] The need to analyze food quality loss has been increasing in recent times due to the increasingly restrictive traceability conditions in the different distribution stages of perishable products. The availability of tools to estimate the quality losses in these logistic phases would help to reduce the waste of food, often discarded due to inadequate preservation conditions. The objective of the project, where this work is framed, is to obtain quality-losses indicators of commodities when they are exposed to undesired thermal variations. These indicators would provide qualitative values of the quality of the perishable merchandise by estimating variations in the shelf life of the commodities. As part of this project, a portable climatic chamber has been designed and built in which controlled thermal cycles can be reproduced during the shelf life of the commodity and, in this way, different quality parameters can be evaluated and related to the preservation conditions. Due to the high number of tests required to obtain reliable indicators, this work proposes the design of an easily reproducible and scalable low-cost chamber where it is feasible to subject the perishable product to controlled thermal alterations during the commercial life of the commodity, and to obtain a dynamic shelf-life as a function of variations in climatic conditions. This work deals with the design, sizing, instrumentation and the different elements that make up the control system, as well as the identification and adjustment of the controller. The results and conclusions show that the controlled climatic chamber developed in this paper, is a useful tool to obtain indicators of quality losses under different climatic conditions

Neutrophil Gelatinase-Associated Lipocalin From Macrophages Plays a Critical Role in Renal Fibrosis Via the CCL5 (Chemokine Ligand 5)-Th2 Cells-IL4 (Interleukin 4) Pathway

International audienceNGAL (neutrophil gelatinase-associated lipocalin; or lipocalin 2, Lcn2) is a novel mineralocorticoid target in the cardiovascular system. We showed that Lcn2 gene invalidation protects against proteinuria and renal injury upon mineralocorticoid excess and we hypothesized that NGAL produced from macrophages promotes the expression of chemoattractant molecules involved these renal lesions. The role of NGAL was analyzed using myeloid-specific (MΦ KO NGAL) Lcn2 knockout mice challenged with uni-nephrectomy, aldosterone, and salt (NAS) for 6 weeks. The role of the CCL5 (chemokine ligand 5) and IL4 (interleukin 4) in kidney fibrosis was studied by administration of the CCL5 receptor antagonist maraviroc or by injections of an anti-IL4 neutralizing antibody. In CTL mice, NAS increased the renal expression of extracellular matrix proteins, such as collagen I, αSMA, and fibronectin associated with interstitial fibrosis which were blunted in MΦ KO NGAL mice. The expression of CCL5 was blunted in sorted macrophages from MΦ KO NGAL mice challenged by NAS and in macrophages obtained from KO NGAL mice and challenged ex vivo with aldosterone and salt. The pharmacological blockade of the CCL5 receptor reduced renal fibrosis and the CD4 + Th cell infiltration induced by NAS. Neutralization of IL4 in NAS mice blunted kidney fibrosis and the overexpression of profibrotic proteins, such as collagen I, αSMA, and fibronectin. In conclusion, NGAL produced by macrophages plays a critical role in renal fibrosis and modulates the CCL5/IL4 pathway in mice exposed to mineralocorticoid excess

Differential Proteomics Identifies Reticulocalbin-3 as a Novel Negative Mediator of Collagen Production in Human Cardiac Fibroblasts

Abstract Cardiac fibrosis is characterized by an excessive accumulation of extracellular matrix components, including collagens. Galectin-3 (Gal-3) and Cardiotrophin-1 (CT-1) are two profibrotic molecules that mediate Aldosterone (Aldo)-induced cardiac fibrosis. However the underlying mechanisms are not well defined. Our aim is to characterize changes in the proteome of human cardiac fibroblasts treated with Aldo, Gal-3 or CT-1 to identify new common proteins that might be new therapeutic targets in cardiac fibrosis. Using a quantitative proteomic approach in human cardiac fibroblasts, our results show that Aldo, Gal-3 and CT-1 modified the expression of 30, 17 and 89 proteins respectively, being common the reticulocalbin (RCN) family members. RCN-3 down-regulation triggered by Aldo, Gal-3 and CT-1 was verified. Treatment with recombinant RCN-3 decreased collagens expression in human cardiac fibroblasts through Akt phosphorylation. Interestingly, CRISPR/Cas9-mediated activation of RCN-3 decreased collagen production in human cardiac fibroblasts. In addition, recombinant RCN-3 blocked the profibrotic effects of Aldo, Gal-3 and CT-1. Interestingly, RCN-3 blunted the increase in collagens expression induced by other profibrotic stimuli, angiotensin II, in human cardiac fibroblasts. Our results suggest that RCN-3 emerges as a new potential negative regulator of collagen production and could represent a therapeutic target in the context of cardiac fibrosis