Improved photoenergy properties of low-emissivity coatings deposited by sputtering with an ion gun treatment

This work studies the effect of ion treatment on low-emissivity (low-e) coatings deposited by magnetron sputtering. Specifically, we have investigated the application of an ion treatment in the dielectric layer before deposition of a layer of silver. This reduces layer roughness which means the silver layer can be deposited with enhanced characteristics. We have also evaluated the etching rate on the SnOx layer due to the ion treatment on already deposit coatings of equal thicknesses. Subsequently, we studied the effects on the coating's photoenergy properties. For equivalent coatings, we found that those treated with ions were more transparent in the visible region, more reflective, and had a lower emissivity, which are essential requirements for low-e coatings applied in architectural glass

Drug development in Parkinson's disease: From emerging molecules to innovative drug delivery systems

Current treatments for Parkinson’s disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly-targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients

Organotypic cultures as tools for optimizing central nervous system cell therapies

Stem cell therapy is a promising treatment for neurological disorders such as cerebral ischemia, Parkinson\u27s disease and Huntington\u27s disease. In recent years, many clinical trials with various cell types have been performed often showing mixed results. Major problems with cell therapies are the limited cell availability and engraftment and the reduced integration of grafted cells into the host tissue. Stem cell-based therapies can provide a limitless source of cells but survival and differentiation remain a drawback. An improved understanding of the behaviour of stem cells and their interaction with the host tissue, upon implantation, is needed to maximize the therapeutic potential of stem cells in neurological disorders. Organotypic cultures made from brain slices from specific brain regions that can be kept in culture for several weeks after injecting molecules or cells represent a remarkable tool to address these issues. This model allows the researcher to monitor/assess the behaviour and responses of both the endogenous as well as the implanted cells and their interaction with the microenvironment leading to cell engraftment. Moreover, organotypic cultures could be useful to partially model the pathological state of a disease in the brain and to study graft-host interactions prior to testing such grafts for pre-clinical applications. Finally, they can be used to test the therapeutic potential of stem cells when combined with scaffolds, or other therapeutic enhancers, among other aspects, needed to develop novel successful therapeutic strategies or improve on existing ones

Effective GDNF brain delivery using microspheres-A promising strategy for Parkinson's disease

Glial cell line-derived neurotrophic factor (GDNF) has shown promise in the treatment of neurodegenerative disorders of basal ganglia origin such us Parkinson\u27s disease (PD). In this study, we investigated the neurorestorative effect of controlled GDNF delivery using biodegradable microspheres in an animal model with partial dopaminergic lesion. Microspheres were loaded with N-glycosylated recombinant GDNF and prepared using the Total Recirculation One-Machine System (TROMS). GDNF-loaded microparticles were unilaterally injected into the rat striatum by stereotaxic surgery two weeks after a unilateral partial 6-OHDA nigrostriatal lesion. Animals were tested for amphetamine-induced rotational asymmetry at different times and were sacrificed two months after microsphere implantation for immunohistochemical analysis. The putative presence of serum IgG antibodies against rat glycosylated GDNF was analyzed for addressing safety issues. The results demonstrated that GDNF-loaded microspheres, improved the rotational behavior induced by amphetamine of the GDNF-treated animals together with an increase in the density of TH positive fibers at the striatal level. The developed GDNF-loaded microparticles proved to be suitable to release biologically active GDNF over up to 5 weeks in vivo. Furthermore, none of the animals developed antibodies against GDNF demonstrating the safety of glycosylated GDNF use

Lesión de la arteria axilar como complicación de una fractura luxación de cuello de húmero

Se presenta un caso de obstrucción por contusión con lesión de la íntima y trombosis secundaria de la arteria axilar en el curso de una fractura luxación de cuello de húmero. La ausencia de pulsos y los signos de isquemia en la extremidad fueron evidentes antes y después de la reducción y estabilización de la lesión osteoarticular. La arteriografía urgente confirmó y localiza la lesión. La resección de la zona obstruida con interposición de un injerto venoso invertido de safena interna consiguió la revascularización del miembro afectado. El paciente evolucionó hacia una recuperación funcional completa.An axillary artery injury as a compplication of a fracture-dislocaton of the shoulder is presented. Pulses were not palpable in the brachial, radial and ulnar arteries. Signs of ischemia of the limb were evidente before and after reduction and fixation of fracture-dislocation. An arteriogram was performed, wich revealed an occluded segment of axillary artery. The injured segment of the artery was then resected and a saphenous vein inter-positivon graft was placed. A satisfactory result was obtained, without functional trouble in the limb

Cardiac tissue engineering for myocardial infarction treatment

Myocardial infarction is one of the major causes of morbidity and mortality worldwide. Current treatments can relieve the symptoms of myocardial ischemia but cannot repair the necrotic myocardial tissue. Novel therapeutic strategies based on cellular therapy, extracellular vesicles, non-coding RNAs and growth factors have been designed to restore cardiac function while inducing cardiomyocyte cycle re-entry, ensuring angiogenesis and cardioprotection, and preventing ventricular remodeling. However, they face low stability, cell engraftment issues or enzymatic degradation in vivo, and it is thus essential to combine them with biomaterial-based delivery systems. Microcarriers, nanocarriers, cardiac patches and injectable hydrogels have yielded promising results in preclinical studies, some of which are currently being tested in clinical trials. In this review, we cover the recent advances made in cellular and acellular therapies used for cardiac repair after MI. We present current trends in cardiac tissue engineering related to the use of microcarriers, nanocarriers, cardiac patches and injectable hydrogels as biomaterial-based delivery systems for biologics. Finally, we discuss some of the most crucial aspects that should be addressed in order to advance towards the clinical translation of cardiac tissue engineering approaches

Expresión y purificación de GDNF para su microencapsulación y aplicación en la enfermedad de Parkinson

La enfermedad de Parkinosn (EP) es un proceso neurodegenerativo del sistema nervioso central que afecta a las neuronas de dopamina de la sustancia negra, núcleo mesoencefálico del control motor. La perdida en el cerebro de este neurotransmisor vital causa los síntomas de la enfermedad. La EP afecta actualmente a 200 de cada 100.000 personas y a 2 de cada 100 entre los mayores de 60 años. En España hay unos 110.000 enfermos. Además, hoy por hoy no se conoce nada que pueda prevenir o curar la enfermedad, ni existe ninguna prueba de laboratorio que permita diagnosticarla. Recentiemente se ha demostrado que el GDNF, factor neurotrófico derivado de las células gliales, es capaz de proteger las neuronas dopaminérgicas e incluso inducir la regeneración del tejido dopaminérgico dañado in vivo. El objetivo del trabajo fue diseñar y desarrolar un método de expresión y purificación de GDNF bioactivo para su posterior microencapsulación y aplicación en la enfermedad de Parkison. El sistema escogido para expresar el GDNF fue el sistema de células eucariotas de mamífero. El vector utilizado para la producción del GDNF en células eucariotas fue el pDEST26 (Tecnología Gateway de Invitrogen). Como sistema de expresión de GDNF se utilizaron las líneas celulares eucariota BHK, 293 y COS 7. Estas células fueron cultivadas en medio D-MEM (Invitrogen) complementado con un 10% de suero fetal bovino (FBS) y Penicilina/Streptomicina (100u/ml) (Invitrogen). La transfección se realizó con Lipofectamine Plus (Invitrogen). Se analizó la expresión de GDNF a nivel de mRNA mediante PCR y a nivel de proteína mediante Western Blot del medio condicionado. Los clones positivos se crecieron en botellas de cultivo de 850 cm2 (Corning) y se realizaron ciclos de recolección del medio. Cada ciclo fue analizado por SDS-PAGE y Western Blot. Para evaluar la actividad de la proteína se ha desarrollado un ensayo de actividad en el que se demuestra la diferenciación morfológica de células PC-12 inducida por GDNF. La presencia de los receptores GFRa1 y RET, necesarios para que el GDNF ejerza su acción, fue determinada por PCR. Las conclusiones obtenidas de este estudio son la obtención de GDNF recombinante a partir de un sistema de expresión en células eucariotas, el desarrollo de un protocolo para su posterior purificación y la obtención de GDNF recombinante biológicamente activo

Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson’s disease

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder afflicting 2% of the population older than 65 years worldwide. Recently, brain organotypic slices have been used to model neurodegenerative disorders, including PD. They conserve brain three-dimensional architecture, synaptic connectivity and its microenvironment. This model has allowed researchers a simple and rapid method to observe cellular interactions and mechanisms. In the present study, we developed an organotypic PD model from rat brains that includes all the areas involved in the nigrostriatal pathway in a single slice preparation, without using neurotoxins to induce the dopaminergic lesion. The mechanical transection of the nigrostriatal pathway obtained during slice preparation induced PD-like histopathology. Progressive nigrostriatal degeneration was monitored combining innovative approaches, such as diffusion tensor magnetic resonance imaging (DT-RMI) to follow fiber degeneration and mass spectrometry to quantify striatal dopamine content, together with bright-field and fluorescence microscopy imaging. A substantia nigra dopaminergic cell number decrease was observed by immunohistochemistry against rat tyrosine hydroxylase (TH) reaching 80% after 2 days in culture associated with a 30% decrease of striatal TH-positive fiber density, a 15% loss of striatal dopamine content quantified by mass spectrometry and a 70% reduction of nigrostriatal fiber fractional anisotropy quantified by DT-RMI. In addition, a significant decline of medium spiny neuron density was observed from days 7 to 16. These sagittal organotypic slices could be used to study the early stage of PD, namely dopaminergic degeneration, and the late stage of the pathology with dopaminergic and GABAergic neuron loss. This novel model might improve the understanding of PD and may represent a promising tool to refine the evaluation of new therapeutic approaches

Terapias neuroprotectoras y neurorestauradoras en el tratamiento de la enfermedad de Parkinson

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Current therapies are symptomatic and, although these therapies are efficacious during the early stages of the disease, they present important side effects when they are used for a long time. The ideal therapy would be the one that would slow down or stop the progression of the disease. This can be achieved, for instance, with neuroprotective and neurorestorative therapies. Among them, cell therapy and therapy with trophic factors such as glial cell line derived neurotrophic factor (GDNF) are the most challenging and promising ones for the scientific community. Although the use of GDNF as a treatment for Parkinson s disease was proposed several years ago, it is necessary to develop alternative strategies to deliver GDNF appropriately to concrete areas of the brain. Here, the use of microspheres as the most suitable tool for the administration of this neurotrophic factor is discussed