Diseño de un ciclo de refrigeración con fines educativos para el análisis de los balances de energía en la parte del refrigerante y en la del aire

El objetivo de este proyecto es diseñar un ciclo de refrigeración didáctico, incluyendo los cálculos teóricos y el proceso de selección de componentes. Para ello se revisarán los conceptos básicos de un ciclo de refrigeración, así como sus componentes incluyendo una introducción a los ciclos de refrigeración estándar, sus componentes principales y accesorios. Además, se describirán tanto las propiedades de los refrigerantes como las diferentes clases existentes, determinando el refrigerante seleccionado para el ciclo. Con propósito educativo se calculará y diseñará un ciclo de refrigeración portátil. Los fundamentos del ciclo serán su compacidad y sencillez para que sirva de modelo a educadores y estudiantes. Con este fin se toma el compresor semi-hermético KM-5X de la serie S de Copeland como punto de partida. La selección del resto de los componentes se hará de acuerdo las limitaciones prácticas y requerimientos impuestos por los propios componentes elegidos y constará de piezas de proveedores como Fischer Kälteklima, Danfoss, Carel, Swagelok, Refairco, L'Unité Hermetique y Reiss Kälte-Klima. La definición completa del sistema será posible debido a los cálculos teóricos que determinarán el punto de funcionamiento del sistema, así como la caída de presión en los intercambiadores de calor para el punto de operación teórico calculado en la fase de diseño. La estimación de las pérdidas de carga ocasionadas en los intercambiadores considerará tanto la parte del refrigerante, dentro de los tubos de ambos intercambiadores, como la del aire, producidas al atravesar transversalmente el aire el banco de tubos que incluye aletas planas en forma de placas continuas. Con esta configuración resultante será posible, en el futuro, hacer mediciones experimentales con el fin de probar o desestimar los cálculos teóricos. Para contribuir al desarrollo teórico del ciclo y facilitar su comprensión y futura utilización se elaborarán un diagrama de tuberías e instrumentación y una recreación del ciclo y sus componentes con el programa Solidworks. Además, se incluirán consejos prácticos para la puesta en marcha del ciclo una vez finalizada su construcción, así como sugerencias para posibles pruebas experimentales a realizar en el mismo en un futuro

Células madre y sus exosomas como terapia avanzada para tratar la hernia incisional: prueba de concepto en modelo murino

An incisional hernia constitutes a tissue protrusion through a traumatic or surgical scar in the abdominal wall. Frequently, the treatment of the incisional hernia, as well as other types of hernia, involves the implantation of a surgical mesh to reinforce the weakened tissue. However, an exacerbated inflammatory response is commonly developed after this implantation, having serious consequences for the patient. Considering the immunomodulatory potential of mesenchymal stem cells (MSCs) and their exosomes (exo-MSCs), in this study we proposed that the administration of these two therapeutic products, together with fibrin sealants that are frequently used to fix surgical meshes, could have a beneficial biological and therapeutic effect that could help to modulate the inflammatory response and improve the success of the surgical mesh implantation. The results obtained in this work showed, in a murine model of incisional hernia, that exo-MSCs reduce M1 inflammatory macrophages infiltration and that there is a predominance of Th2-related cytokines in the surrounding tissue of MSCs or exo-MSCs treated meshes, favoring the macrophage polarization towards a M2 anti-inflammatory phenotype. This study concludes that mesh fixation with fibrin sealants co-administered with MSCs or exo-MSCs would have a beneficiary effect on the treatment of incisional hernia in terms of reduction of the inflammatory response and modulation of the foreign body reaction.Una hernia incisional consiste en una protrusión de tejido a través de una cicatriz traumática o quirúrgica en la pared abdominal. El tratamiento de este y de otros tipos de hernias pasa frecuentemente por la implantación de una malla quirúrgica para reforzar el tejido debilitado. Sin embargo, a menudo se produce una respuesta inflamatoria exacerbada que desemboca en diferentes complicaciones, teniendo consecuencias graves para el paciente.Considerando el potencial inmunomodulador de las células madre mesenquimales (MSCs) y de sus exosomas (exo-MSCs), en este estudio planteamos que la administración de ambos productos terapéuticos, conjuntamente con los selladores de fibrina que se utilizan frecuentemente para la fijación de las mallas quirúrgicas, podría ejercer un efecto biológico y terapéutico que ayudara a controlar esa respuesta inflamatoria y mejorara, por tanto, el éxito del tratamiento con mallas quirúrgicas.Los resultados obtenidos en este estudio mostraron, en un modelo murino de hernia incisional, que los exo-MSCs reducen la infiltración de macrófagos inflamatorios M1 y que existe una predominancia de citoquinas relacionadas con la respuesta Th2, y con ello, con la polarización de macrófagos hacia un fenotipo M2 antiinflamatorio, en el tejido circundante a las mallas en las que se vehicularon MSCs o sus exosomas.Este estudio concluye que la fijación de mallas quirúrgicas con selladores de fibrina combinados con MSCs o exo-MSCs tendría un efecto beneficioso en el tratamiento de la hernia incisional, en términos de reducción de la respuesta inflamatoria y modulación de una reacción exacerbada frente a un cuerpo extraño

Structural characterization of PaaX, the main repressor of the phenylacetate degradation pathway in Escherichia coli W: A novel fold of transcription regulator proteins

15 p.-8 fig.-2 tab.PaaX is a transcriptional repressor of the phenylacetic acid (PAA) catabolic pathway, a central route for bacterial aerobic degradation of aromatic compounds. Induction of the route is achieved through the release of PaaX from its promoter sequences by the first compound of the pathway, phenylacetyl-coenzyme A (PA-CoA). We report the crystal structure of PaaX from Escherichia coli W. PaaX displays a novel type of fold for transcription regulators, showing a dimeric conformation where the monomers present a three-domain structure: an N-terminal winged helix-turn-helix domain, a dimerization domain similar to the Cas2 protein and a C-terminal domain without structural homologs. The domains are separated by a crevice amenable to harbour a PA-CoA molecule. The biophysical characterization of the protein in solution confirmed several hints predicted from the structure, i.e. its dimeric conformation, a modest importance of cysteines and a high dependence of solubility and thermostability on ionic strength. At a moderately acidic pH, the protein formed a stable folding intermediate with remaining α-helical structure, a disrupted tertiary structure and exposed hydrophobic patches. Our results provide valuable information to understand the stability and mechanism of PaaX and pave the way for further analysis of other regulators with similar structural configurations.This research was funded by the following sources: Grants PID2019-105126RB-I00, PID2022-139209OB-C21 (MCIN/AEI/10.13039/501100011033/and ERDF A way of making Europe), TED2021-129747B-C22 (AEI/10.13039/501100011033/NextGenerationEU/PRTR) and CIBER-Consorcio Centro de Investigación Biomédica en Red (CIBERES, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Spain) to JMS; grants PID2020-115331GB-100 funded by MCIN/AEI/10.13039/501100011033 and CRSII5_198737/1 (Swiss National Science Foundation) to JAH; grant PID2021-128751NB-I00 (MICINN/AEI/FEDER/UE) to IU, and grant RYC2021-030916-I by the Spanish Agencia Estatal de Investigación to RM. VMH-R was supported by a FPU PhD fellowship from Spanish Ministerio de Educación y Ciencia.Peer reviewe

Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy

BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab

PDGF-BB serum levels are decreased in adult onset Pompe patients

Adult onset Pompe disease is a genetic disorder characterized by slowly progressive skeletal and respiratory muscle weakness. Symptomatic patients are treated with enzymatic replacement therapy with human recombinant alfa glucosidase. Motor functional tests and spirometry are commonly used to follow patients up. However, a serological biomarker that correlates with the progression of the disease could improve follow-up. We studied serum concentrations of TGFβ, PDGF-BB, PDGF-AA and CTGF growth factors in 37 adult onset Pompe patients and 45 controls. Moreover, all patients performed several muscle function tests, conventional spirometry, and quantitative muscle MRI using 3-point Dixon. We observed a statistically significant change in the serum concentration of each growth factor in patients compared to controls. However, only PDGF-BB levels were able to differentiate between asymptomatic and symptomatic patients, suggesting its potential role in the follow-up of asymptomatic patients. Moreover, our results point to a dysregulation of muscle regeneration as an additional pathomechanism of Pompe disease

Ischemia-reperfusion injury in a rat microvascular skin free flap model: A histological, genetic, and blood flow study.

Ischemia reperfusion injury is associated with tissue damage and inflammation, and is one of the main factors causing flap failure in reconstructive microsurgery. Although ischemia-reperfusion (I/R) injury is a well-studied aspect of flap survival, its biological mechanisms remain to be elucidated. To better understand the biological processes of ischemia reperfusion injury, and to develop further therapeutic strategies, the main objective of this study was to identify the gene expression pattern and histological changes in an I/R injury animal model. Fourteen rats (n = 7/group) were randomly divided into control or ischemia-reperfusion group (8 hours of ischemia). Microsurgical anastomoses were objectively assessed using transit-time-ultrasound technology. Seven days after surgery, flap survival was evaluated and tissue samples were harvested for anatomopathological and gene-expression analyses.The I/R injury reduced the survival of free flaps and histological analyses revealed a subcutaneous edema together with an inflammatory infiltrate. Interestingly, the Arginase 1 expression level as well as the ratio of Arginase 1/Nitric oxide synthase 2 showed a significant increase in the I/R group. In summary, here we describe a well-characterized I/R animal model that may serve to evaluate therapeutic agents under reproducible and controlled conditions. Moreover, this model could be especially useful for the evaluation of arginase inhibitors and different compounds of potential interest in reconstructive microsurgery

Intracoronary Administration of Microencapsulated HGF in a Reperfused Myocardial Infarction Swine Model

Therapy microencapsulation allows minimally invasive, safe, and effective administration. Hepatocyte growth factor (HGF) has angiogenic, anti-inflammatory, anti-apoptotic, and anti-fibrotic properties. Our objective was to evaluate the cardiac safety and effectiveness of intracoronary (IC) administration of HGF-loaded extended release microspheres in an acute myocardial infarction (AMI) swine model. An IC infusion of 5 × 106 HGF-loaded microspheres (MS+HGF, n = 7), 5 × 106 placebo microspheres (MS, n = 7), or saline (SAL, n = 7) was performed two days after AMI. TIMI flow and Troponin I (TnI) values were assessed pre- and post-treatment. Cardiac function was evaluated with magnetic resonance imaging (cMR) before injection and at 10 weeks. Plasma cytokines were determined to evaluate the inflammatory profile and hearts were subjected to histopathological evaluation. Post-treatment coronary flow was impaired in five animals (MS+HGF and MS group) without significant increases in TnI. One animal (MS group) died during treatment. There were no significant differences between groups in cMR parameters at any time (p > 0.05). No statistically significant changes were found between groups neither in cytokines nor in histological analyses. The IC administration of 5 × 106 HGF-loaded-microspheres 48 h post-AMI did not improve cardiac function, nor did it decrease inflammation or cardiac fibrosis in this experimental setting

Intrapericardial Administration of Mesenchymal Stem Cells in a Large Animal Model: A Bio-Distribution Analysis

<div><p>The appropriate administration route for cardiovascular cell therapy is essential to ensure the viability, proliferative potential, homing capacity and implantation of transferred cells. At the present, the intrapericardial administration of pharmacological agents is considered an efficient method for the treatment of cardiovascular diseases. However, only a few reports have addressed the question whether the intrapericardial delivery of Mesenchymal Stem Cells (MSCs) could be an optimal administration route. This work firstly aimed to analyze the pericardial fluid as a cell-delivery vehicle. Moreover, the <i>in vivo</i> biodistribution pattern of intrapericardially administered MSCs was evaluated in a clinically relevant large animal model. Our <i>in vitro</i> results firstly showed that, MSCs viability, proliferative behavior and phenotypic profile were unaffected by exposure to pericardial fluid. Secondly, <i>in vivo</i> cell tracking by magnetic resonance imaging, histological examination and Y-chromosome amplification clearly demonstrated the presence of MSCs in pericardium, ventricles (left and right) and atrium (left and right) when MSCs were administered into the pericardial space. In conclusion, here we demonstrate that pericardial fluid is a suitable vehicle for MSCs and intrapericardial route provides an optimal retention and implantation of MSCs.</p></div

<i>In vivo</i> cell tracking of intrapericardially delivered pBM-MSCs by cardiac-MRI in non-infarcted hearts.

<p>A total of 100x10⁶ SPIO-labeled pBM-MSCs cells were injected into the pericardial cavity of healthy Large White pigs. The MRI was performed using a 1.5T magnetic resonance technology. Images were acquired in four chamber views (A-D) and using a T2-star gradient echo image (E-H). Images taken at day 3 post injection (B-D, F-H) are represented together with the corresponding control images (A, E) taken before injection. The arrows indicate the location of SPIO-labeled cells.</p

Y chromosome detection of intrapericardially delivered pBM-MSCs.

<p>The pBM-MSCs from a male donor were detected in the heart by Y chromosome amplification. (A) In order to determine the sensitivity of PCR amplification, pBM-MSCs from a male donor were mixed with 10⁶ pBM-MSCs from a female donor at the indicated ratios. Genomic DNA was extracted and subjected to PCR amplification using Y chromosome specific primers. The PCR allowed the detection of male cells with a sensitivity of 100–1000 cells per 10⁶ female cells. (B) Female pigs were intrapericardially injected with male-derived pBM-MSCs. At day 7, the animals were euthanized and heart samples were collected for PCR analysis. As negative and positive controls, the genomic DNA from female and male pBM-MSCs cells were amplified. LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle, PV = pericardium on the right and left ventricles, PA = pericardium on the right and left atrium.</p